PMID- 8520548
TI  - Hurst analysis in the study of ion channel kinetics.
AB  - Ion channels are protein molecules which can assume distinct open and closed
      conformational states. The transitions between these states can be controlled by
      the electrical field, ions and/or drugs. Records of unitary current events show
      that short open-time intervals are frequently adjacent to much longer closed-time
      intervals, and vice-versa, suggesting that the kinetic process has memory, i.e.,
      the intervals are correlated in time. Here the rescaled range analysis (R/S Hurst
      analysis) is proposed as a method to test for correlation. Simulations were
      performed with a two-state Markovian model, which has no memory. The calculated
      Hurst coefficients (H) presented a mean +/- SD value of 0.493 +/- 0.025 (N =
      100). For the Ca(2+)-activated K+ channels of Leydig cells, H was equal to 0.75,
      statistically different (1% level) from that calculated for the memoryless
      process. Randomly shuffling the experimental data resulted in an H = 0.55, not
      significantly different (1% level) from that found for the two-state Markovian
      model. For a linear three-state Markovian model, H was equal to 0.548 +/- 0.017
      (N = 15), again not significantly different (1% level) from that of the
      memoryless process. Although the three-state Markovian model adequately describes
      the open- and closed-time distributions, it does not account for the correlation
      found in this Ca(2+)-activated K+ channel. Our results illustrate the efficacy of
      the R/S analysis in determining whether successive opening and closing events are
      correlated in time and can be of help in deciding which model should be used to
      describe the kinetics of ion channels.

PMID- 8520549
TI  - Streptozotocin diabetes modifies arterial pressure and baroreflex sensitivity in
      rats.
AB  - Although an increased prevalence of hypertension is associated with insulin
      dependent diabetes, little is known about the effect of streptozotocin (STZ)
      diabetes on arterial pressure (AP) regulation in rats. Changes in AP induced by
      STZ, as well as associated factors in blood pressure regulation such as
      baroreflex sensitivity, plasma renin activity (PRA), plasma glucose and insulin
      levels and endothelium participation, were studied in male Wistar rats weighing
      287 +/- 10 g. The same seven conscious rats were used for all measurements before
      and after STZ diabetes. AP pulses were stored on a videotape recorder and
      processed by a data acquisition system. Baroreflex sensitivity was evaluated by
      measuring heart rate (HR) changes induced by AP variations produced by
      phenylephrine and sodium nitroprusside injection. The effect of inhibition of
      nitric oxide synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg
      i.v. bolus plus infusion at 20 mg kg-1 h-1) on AP was evaluated in another set of
      rats (6 normal and 5 submitted to STZ treatment). STZ induced hyperglycemia (306
      +/- 19 mg/dl), a reduction in mean arterial pressure (MAP, from 116 +/- 5 to 101
      +/- 4 mmHg) and no changes in HR (320 +/- 10 vs 298 +/- 14 bpm). The tachycardic
      response to arterial pressure decreases was impaired (-2.29 +/- 0.5 vs -4.5 +/-
      0.7 bpm/mmHg, in control) while the bradycardic response to arterial pressure
      increases was unchanged. Pressure responsiveness to phenylephrine was impaired
      after STZ (3.78 +/- 0.4 vs 6.73 +/- 0.8 mmHg microU-1 ml-1, in control).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520550
TI  - [Current opinions on the value of tuberculin tests in diagnosis of tuberculosis].

PMID- 8520551
TI  - [Weaning from mechanical ventilation in patients with exacerbations of chronic
      respiratory insufficiency--personal experience].
AB  - Nineteen patients with exacerbation of chronic respiratory insufficiency treated
      with mechanical ventilation were included in the study. The mean weaning time
      from the respirator was 15.9 days (+/- 12.1), ranging from 2 to 49 days. Success
      was met in 9 patients using inspiratory pressure support (IPS), in 2 synchronized
      intermittent mandatory ventilation (SIMV), in 8 the simplest model (stepwise
      prolongation of spontaneous ventilation during continuous mechanical ventilation-
      CMV/SV). All options were used in the same patients throughout the weaning
      procedure. The use of IPS led to a successful weaning in those patients in whom
      other options (CMV/SV, SIMV) were not fortunate. The application of IPS was begun
      at 40 cm H2O, gradually decreasing the support pressure. The duration of
      spontaneous breathing in all weaning options was not only depended on gasometric
      values, continuous SaO2 monitoring, but mainly on the patients' subjective sense
      of fatigue. The impression of exhaustion preceded the changes of gasometric
      parameters and fall of SaO2. The basis of effective weaning is proper selection
      of respirator parameters, providing almost identical gasometric values if
      individual patient's to those prior exacerbation of chronic respiratory
      insufficiency. The duration of weaning negatively correlated (0.25) with FEV1
      values.

PMID- 8520552
TI  - [Pneumonia in patients after extracorporeal circulation].
AB  - Hospital infections are still an important problem of to-days medicine. The most
      common and dangerous one is pneumonia. The purpose of this study was to determine
      the cause of pneumonia in patients operated on under extracorporeal circulation.
      It was proved that micro-organisms responsible for pneumonia in our patients were
      Pseudomonas sp. and Staphylococcus aureus. No correlation between the bacterial
      flora cultured from the air in operating theatre and post-op. ward and bacterial
      flora responsible for pneumonia was found. It can be infer that pulmonary
      infections were rather caused by hospital cross-infections or endogenic
      infections in colonized patients.

PMID- 8520553
TI  - [Copper and ceruloplasmin concentrations in serum of infants with pneumonia].
AB  - Copper constitute one of the most significant trace metal for the organism.
      Numerous biochemical processes depend on this element. It constitute component
      and activator of many enzymes. In blood serum copper is bound with ceruloplasmin.
      In this work the behavior of copper and ceruloplasmin concentration in blood
      serum in the course of pneumonia in infant was investigated. 36 infants aged 2
      months trough 12 months with pneumonia were included in the study. The control
      group consisted of 14 healthy infants. Tests were conducted thrice in the group
      of sick infants. In the acute stage of pneumonia in sick infants the authors
      showed higher copper and ceruloplasmin concentration values. After the therapy
      ended the concentration of those values were similar to those in the control
      group.

PMID- 8520554
TI  - [Phenotype of lymphocytes in bronchoalveolar lavage fluid of patients with lung
      fibrosis in the course of scleroderma].
AB  - Patients with systemic sclerosis frequently develop interstitial lung disease.
      One of the major sites of pathogenic activity are lymphocytes from lung
      interstitium. The purpose of this work was phenotype analysis of lymphocytes in
      bronchoalveolar lavage fluid (BALF) with flow cytofluorometry. We found an
      increase number of CD8+ lymphocytes and CD8+/T ratio, and an reduced CD4+/CD8+
      ratio in patients when compared to healthy volunteers. The diffusing capacity
      (DLCO) correlated positive with percentage of neutrophils and HLA-DR+
      lymphocytes. There are the features of mixed type alveolitis in patients with
      short disease duration. We found increase number of lymphocytes, neutrophils,
      CD8+ lymphocytes, HLA-DR+ lymphocytes and CD25+ lymphocytes in this patients. We
      concluded that fluorocytometric BALF analysis may be useful for the diagnosis and
      management of lung involvement in patients with scleroderma before the treatment.

PMID- 8520555
TI  - [Recurrence of pulmonary sarcoidosis].
AB  - From September 1960 to December 1992, 2021 patients with pulmonary sarcoidosis
      were registered in our Sarcoidosis Clinic. 462 patients were treated with
      steroids. Treatment was initiated either because of radiological evidence of
      disease progression after 6 months observation, lack of radiological improvement
      together with abnormalities of pulmonary function, presence of extra-pulmonary
      lesions. In 42 cases (9% of treated group); 19 men and 23 women, mean age 35
      years, relapse of disease was observed from 6 months to 6 years after completion
      of treatment. At the entry to the first treatment 11 patients were assessed as
      having stage I disease, 30 as stage II and one as stage III. In 16 subjects of
      this group (38%), extra-pulmonary lesions were presents; skin lesions in 8 cases
      and enlarged peripheral lymph nodes in 6. After initial treatment, radiological
      and clinical improvement was observed in 32 patients. The second treatment
      results in radiological improvement in 38 patients, 10 are being still treated.
      In 4 cases a second relapse was noted. In three patients regression of pulmonary
      changes was achieved, in one case stabilization of the disease was observed.

PMID- 8520556
TI  - [Pulmonary mycobacteriosis in personal clinical material].
AB  - There were analyzed 23 cases with non-tuberculosis mycobacterium infection,
      including 19 with mycobacteriosis and 4 with symptoms of colonisation. Among them
      nine patients were treated less than 6 months, but 14 ones were treated with
      different antituberculotic schedules during 6-24 months. In 9 patients of this
      group a sputum negativity was achieved. On the other hand, recurrents of
      mycobacteriosis was determined in 3 patients. Total observation period was
      extended from 2 to 6 years.

PMID- 8520557
TI  - [Geography of lung cancer incidence among women and men of Upper Silesia in the
      years 1986-1990].
AB  - During a five period (1986-1990) in Katowice province (Upper Silesia) there were
      6,140 cases of lung cancer in males and 1,039 females recorded. The standardized
      (according to age structure of the world population) incidence of lung cancer in
      both groups, in 93 administrative units (45 cities, 48 communities) significantly
      vary and are geographically unevenly distributed. The incidence in selected areas
      in males can be compared with values characterizing regions of the world with
      highest indices (> 95 per 100,000); whereas in females the incidence of lung
      cancer is much lower. The prognosis for lung cancer incidence in the Upper
      Silesia, according to the regression analysis is pessimistic.

PMID- 8520558
TI  - [Acetylation phenotype in patients with lung cancer].
AB  - The acetylation phenotype is genetically predetermined. It might influence the
      development of several diseases. It can also be changed by the active process of
      diseases. The aim of the study was to determinate the acetylation phenotype of
      individuals with lung cancer. Sulfadimidine acetylation study was undertaken in
      30 patients with lung cancer and 30 individuals of control group. There is a
      significantly higher proportion of slow acetylators in the group of patients with
      lung cancer than in those without the disease.

PMID- 8520559
TI  - [Macroscopic evaluation of bronchial mucosa and histological diagnosis in
      relation to localization of neoplastic changes in the bronchial tree].
AB  - In 140 lung cancer patients fiberoptic bronchoscopy with biopsy and BAL procedure
      were performed in diagnostic process. Obtained results of macroscopic changes
      were analyzed in relation to histological diagnosis and localization in the
      bronchial tree (central and peripheral). Squamous cell lung cancer was the most
      often diagnosed in central localized tumors and adenocarcinoma in peripheral
      ones. Macroscopic changes were more evident and more characteristic for cancer
      process in central localized tumors. In peripheral changes non-characteristic,
      inflammatory-like symptoms were determined.

PMID- 8520560
TI  - [Prognostic value of neuron enolase levels in serum of patients with lung
      neoplasms].
AB  - The aim of this study was to assess a prognostic value of serum specific enolase
      (NSE) measurement in lung cancer patients. Total number of 105 patients entered
      the study, including 36 patients with small cell carcinoma and 69 patients with
      non small cell carcinoma (21-squamous cell carcinoma, 32-adenocarcinoma, 14-large
      cell carcinoma). Elevated NSE level was observed in 47 (44.8%) patients: in 75%
      of SCLC patients and 29% of NSCLC patients (p < 0.001). Median survival in NSCLC
      patients with elevated NSE levels was 27 weeks and in those with normal values-59
      weeks. The probability of one year survival in both groups was 22% and 45%
      respectively (p = 0.27). Median survival in SCLC patients with elevated NSE test
      was 30 weeks and in those normal levels-61 weeks and the probability of one years
      survival in both groups was 26% and 62%, respectively (p = 0.34).

PMID- 8520561
TI  - [The role of radiotherapy in combined treatment of limited small cell lung cancer
      in relation to results of induction chemotherapy].
AB  - The comparison between results of chemotherapy (ChT) and ChT plus radiotherapy
      (RT) was performed in the group of 124 patients with limited SCLC. After
      induction ChT 25% pts obtained CR, 54%-PR and 21% did not respond. In 69 pts ChT
      was continued and in 55 others RT was added to ChT. The number of patients in
      whom tumor response was observed increased significantly after addition of RT to
      ChT. The degree of complete response had important impact on survival time. The
      pts who obtained CR had significantly longer survival time than those who
      achieved only PR or NR. Median survival time was very similar in both groups (13
      months after ChT alone and 15 months after ChT plus RT). This was also true for
      the groups of patients who obtained CR after completion of treatment. Achievement
      of complete response is the most important factor for good prognosis. RT is
      indicated in those patients who achieved only PR after induction ChT.

PMID- 8520562
TI  - [Implantation of a LGM suprarenal vena cava filter--case report].
AB  - In the case of 53 years old woman LGM filter was inserted over renal veins.
      Indications for those procedures were: vena cava thrombosis in distal part of
      vena cava what not allowed to place filter below renal veins, malignancy, planned
      surgery, proximal deep vein thrombosis and past history of pulmonary embolism.
      Indications for suprarenal placement of vena cava filters and results of such as
      procedure were discussed.

PMID- 8520563
TI  - [Prophylactic use of the LGM filter in a patient with a recurrent clinically
      acute massive pulmonary embolism complicated by pericarditis--case report].
AB  - Case of recurrent, clinically acute massive pulmonary embolism treated with rtPA
      (administered 0.6 mg/kg, during 10 minutes simultaneously with heparin) is
      presented. Minimal clinical improvement was observed after mentioned procedure.
      Good clinical response was achieved after LGM filter insertion into vena cava
      inferior. Clinical course was complicated by Dressler-like syndrome successfully
      treated with steroids. Problems of massive pulmonary embolism, vena cava filter
      prophylaxis and pericardial complication of pulmonary embolism are discussed.

PMID- 8520564
TI  - [A case of undiagnosed pneumonia complicated by chronic pleural empyema].

PMID- 8520565
TI  - [A case of coexisting tuberculous otitis media and pulmonary tuberculosis].
AB  - We described the case of otitis media tuberculosa at the patient suffered from
      lung tuberculosis. Because of rare appearance and nonspecific running OMT is
      difficult to diagnose and correct treatment. At the described case fast and exact
      diagnosis maid possible, successfully ended, treatment.

PMID- 8520566
TI  - [Ultrasonographic examination of the heart as a basis for determining the cause
      of inflammatory infiltration changes in the lungs].
AB  - Diagnostic difficulties found in a 41 year old female presenting with fever,
      chills, fainting spells, tachycardia, hypotension, interstitial consolidation in
      both lungs and enlargement of the cardiac silhouette on a chest radiogram are
      discussed. Unsuccessful antibacterial and antituberculous therapy led to a
      supposition of a collagen disease. The diagnosis of a bacterial endocarditis with
      bacterial pulmonary emboli was made basing on determination of bacterial
      vegetation on cusps of the tricuspid valve.

PMID- 8520567
TI  - [Metabolic disturbances and collagen distribution in interstitial pulmonary
      fibrosis].

PMID- 8520568
TI  - [Pulmonary eosinophilic granuloma (histiocytosis X)].

PMID- 8520569
TI  - [Transcutaneous pulse oximetry].

PMID- 8520570
TI  - [Macrophages and lymphocytes in immune reactions during the course of
      tuberculosis].

PMID- 8520571
TI  - The effect of calcium levels on synaptic proteins. A study on VAT-1 from Torpedo.
AB  - In this study we compare major synaptic proteins from Torpedo electric organ to
      their homologues from mammalian brain. Most of these proteins are members of
      small gene families. We demonstrate a high degree of evolutionary conservation of
      most synaptic proteins. However, in the electric organ each gene family is
      represented only by a single member. We focus on VAT-1, a major protein of the
      vesicle membrane in Torpedo. VAT-1 is located on the synaptic vesicle membrane
      and is highly concentrated on the plasma membrane following the application of
      alpha-latrotoxin. Taking advantage of the relative simplicity of Torpedo
      synapses, we performed an in vitro study on the properties of VAT-1 affected by
      changes in Ca2+ levels. VAT-1 is a low affinity Ca2+ binding protein whose
      ability to bind Ca2+ resides mainly, but not entirely, on the carboxy-terminal
      domain of the protein. In the presence of Ca2+, the protein is organized in a
      high molecular mass complex, which is destabilized by depleting Ca2+. This effect
      occurs only by chelating Ca2+ ions, but not with other divalent ions. VAT-1 is
      not complexed to any of the proteins which were implicated in the docking/fusion
      complex such as VAMP, synaptophysin or syntaxin, regardless of Ca2+ levels.
      Dependence of the stability of protein complexes on Ca2+ levels is also
      demonstrated on Torpedo n-Sec1. The possible physiological implications of such
      Ca2+ dependence are discussed.

PMID- 8520572
TI  - Genetic dissection of the molecular mechanisms of transmitter vesicle release
      during synaptic transmission.
AB  - Over the last few years there has been rapid progress in our understanding of the
      molecular mechanisms of synaptic transmission. This advance is largely due to the
      convergence of biochemical and genetic approaches to identify a discrete set of
      synaptic proteins associated with transmitter vesicles and their specialized
      fusion sites in the presynaptic membrane. The fruitfly, Drosophila melanogaster,
      is an attractive system to further such studies where we can combine
      sophisticated molecular genetic manipulations with direct observation of synaptic
      phenotypes at the well-characterized neuromuscular junction (NMJ). So far, five
      essential synaptic proteins have been identified in Drosophila and genetically
      modified or removed from the synapse: synaptotagmin, synaptobrevin (also called
      VAMP), syntaxin, Rop (Drosophila n-sec1 homologue) and cysteine string protein
      (csp). We are presently characterizing the functional roles of these identified
      proteins using electrophysiological and ultrastructural analyses of genetic
      mutants. In this article I review our current knowledge of these five proteins in
      Drosophila and discuss their possible functional roles in the molecular machinery
      governing synaptic transmission.

PMID- 8520573
TI  - Do caged-Ca2+ compounds mimic the physiological stimulus for secretion?
AB  - We measured the exocytotic response induced by a rapid and global increase in the
      concentration of Ca2+ or GTP gamma S (achieved by flash photolysis of caged
      compounds) in mast cells and chromaffin cells. Secretion was measured by
      following both cell membrane capacitance and amperometry. When Ca2+ was used to
      trigger secretion, we observed an immediate increase in capacitance, however, the
      first amperometric spike observed was delayed with respect to the change in
      capacitance (approximately 5 s in mast cells and approximately 0.6 s in
      chromaffin cells). In contrast, when GTP gamma S was used to trigger secretion,
      no such discrepancy was seen, both measurements reported a secretory response
      that was similarly delayed with respect to the stimulus. These data suggest that
      the capacitance increase, when triggered by a large Ca2+ step, reports events
      that do not result in the fusion of vesicles containing oxidizable substances.
      These results contrast with the smaller secretory responses evoked by the
      transient opening of Ca2+ channels. Under these more physiological conditions,
      pulsed-laser imaging studies revealed that the Ca2+ influx was localized to
      discrete areas at the plasma membrane. Thus the Ca2+ stimulus triggered by DM
      nitrophen fails to reproduce the small localized changes seen during a
      physiological stimulation and creates an artifactual non-secretory capacitive
      response.

PMID- 8520574
TI  - Time resolved calcium microdomains and synaptic transmission.
AB  - The time course for the calcium entry that triggers release was studied at the
      squid giant synapse by imaging light emission from n-aequorin-J intracellularly
      injected into the presynaptic terminal. The imaging utilized a video system
      capable of acquiring 4000 frames per second. The results indicate that the
      calcium entry triggered by action potentials reaches a peak within 200
      microseconds and has an overall duration of close to 800 microseconds, closely
      matching the duration of the presynaptic calcium current determined by voltage
      clamp results under similar conditions.

PMID- 8520575
TI  - Role of myosin in neurotransmitter release: functional studies at synapses formed
      in culture.
AB  - To determine the functional role of presynaptic proteins in the neurotransmitter
      release, I have employed cholinergic synapses formed between superior cervical
      ganglion neurons in culture. These synapses expressed proteins characteristic of
      mature synapses: immunofluorescence staining showed the presence of
      synaptophysin, synaptotagmin, VAMP/synaptobrevin-2, syntaxin and neurexin. The
      function of these proteins seems to be similar to that of mature synapses because
      botulinum neurotoxins A, E and C1 inhibited neurotransmitter release evoked by
      presynaptic action potentials. With this preparation, I have obtained evidence
      supporting roles for myosin II and myosin light chain kinase in neurotransmitter
      secretion. Acetylcholine release was inhibited by introduction of antibody
      against myosin II or inhibitors of myosin light chain kinase. This evidence
      suggests a model in which myosin light chain kinase phosphorylates myosin, and
      the resultant change in actin-myosin interactions is involved in some steps of
      transmitter release.

PMID- 8520576
TI  - Cysteine string proteins and presynaptic function.
AB  - A brief review is presented of investigations of a novel family of synaptic
      vesicle proteins, the cysteine string proteins (csps). Studies of csp mutants in
      Drosophila reveal that csps are crucial components of the excitation-secretion
      machinery at nerve terminals. Current data cannot distinguish between a primary
      role of csps in modulating calcium ion influx at the nerve terminal versus a more
      direct role in the exocytotic cascade. In this context, the remarkable post
      translational modification of csps, namely the fatty acylation of as many as 12
      of the 13 cysteine residues of the Torpedo protein, suggests that csps may
      participate more directly in the process of membrane fusion that underlies
      exocytosis. This would be achieved by using the fatty acyl chains of the csps as
      templates for 'lipid flow' that would allow the fusion of vesicular and plasma
      membranes. These hypotheses provide a useful framework for empirical tests of the
      role of csps in nerve terminal function.

PMID- 8520577
TI  - Proteolysis of a 34 kDa phosphoprotein coincident with a decrease in protein
      kinase activity during the erythrocytic schizont stage of the malaria parasite.
AB  - Protein phosphorylation events may play important roles in the replication and
      differentiation of the malarial parasite. Investigations into the lability of a
      Plasmodium protein kinase revealed that a 34 kDa parasite phosphoprotein is
      rapidly converted into a 19 kDa fragment. Coincident with this conversion is a
      nearly total loss of a protein kinase activity, as determined from the
      phosphorylation of endogenous protein substrates. Both the conversion of the 34
      kDa protein to the 19 kDa protein and the loss of protein kinase activity are
      inhibited by thio-protease inhibitors. The presence of low levels of the intact
      34 kDa protein restores the protein kinase activity to almost maximum levels.
      However, it was not possible to demonstrate protein kinase activity associated
      with the 34 kDa protein, thus suggesting that the 34 kDa protein is probably an
      activator or regulator of the protein kinase activity and not a protein kinase.
      The conversion to the 19 kDa fragment also occurs in vivo and only during the
      schizont stage prior to the appearance of ring forms. During this same period the
      protein kinase activity decreases suggesting that the proteolytic processing of
      the 34 kDa protein may be a physiological regulator of the protein kinase.

PMID- 8520578
TI  - Alternation of actinosporean and myxosporean phases in the life cycle of
      Zschokkella nova (Myxozoa).
AB  - Experimental evidence has been gathered to show that the life cycle of the
      myxozoan gallbladder parasite Zschokkella nova Klokacewa, 1914, which infects the
      fish Carassius carassius, has a complex life cycle with alternation of two hosts
      (fish and Oligochaeta) and two developmental phases (myxosporean and
      actinosporean). The gut epithelium of the oligochaete, Tubifex tubifex, exposed
      experimentally to Z. nova, obtained from C. carassius, became infected with
      organisms resembling Actinosporea. The spore structure and cube-like network of
      the interconnected spores is reminiscent of Siedleckiella silesica Janiszewska,
      1952, although the spores are very different in size and number of sporoplasm
      nuclei. The life cycle of Z. nova resembles that of the whirling disease agent
      Myxosoma cerebralis described by Wolf and Markiw, which also alternates between
      fish and oligochaete hosts.

PMID- 8520579
TI  - Uptake and metabolism of L-serine by Pneumocystis carinii carinii.
AB  - Serine is an important amino acid that is utilized in the biosyntheses of
      proteins and lipids. It is directly incorporated into the head group of
      phosphatidylserine, which in turn can be converted to other phospholipids. Also,
      it is required for the formation of long chain bases, precursors of
      sphingolipids. Uptake and incorporation of radiolabeled serine into both lipids
      and acid-precipitable material were demonstrated in Pneumocystis carinii carinii
      organism preparations freshly isolated from infected rat lungs. Radioactivity in
      proteins was about double that observed in lipids. Liquid scintillation
      spectrometry of metabolically radiolabeled lipids separated by thin-layer
      chromatography showed 53% of the total radioactivity were in phosphatidylserine,
      12% in phosphatidylethanolamine, 24% in ceramides, and 11% in long chain bases
      and other compounds. Four long chain bases were detected by thin-layer
      chromatography in hydrolyzed P. carinii ceramides metabolically labeled with
      radioactive serine. Phytosphingosine and dihydrosphingosine were tentatively
      identified by their migrations on thin-layer plates. Radiolabeled ethanolamine
      was incorporated into P. carinii phosphatidylethanolamine, but relatively low
      incorporation of radiolabeled choline into phosphatidylcholine occurred. The
      observations made in this study indicated that P. carinii has the biosynthetic
      capacity to metabolize phospholipid head groups and to de novo synthesize
      sphingolipids. L-Cycloserine and beta-Cl-D-alanine, inhibitors of long chain base
      synthesis, reduced the incorporation of serine into P. carinii long chain bases
      and ceramides, which supported the conclusion that the pathogen synthesizes
      sphingolipids.

PMID- 8520580
TI  - Analysis of genetic diversity at the arom locus in isolates of Pneumocystis
      carinii.
AB  - The DNA sequences of a portion of the 5-enolpyruvyl shikimate phosphate synthase
      domain of the arom gene, encoding the pentafunctional AROM protein, were
      determined from isolates of Pneumocystis carinii from five mammalian host species
      (rat, human, ferret, rabbit and mouse). High levels of genetic divergence were
      found among P. carinii derived from different host species, 7-22% at the DNA
      sequence level, and 7-26% at the derived amino acid sequence level. Two separate
      and distinct sequences were isolated from infected ferret lungs. Low levels of
      divergence were seen in human-derived organisms.

PMID- 8520581
TI  - Phylogeny of the large extrachromosomal DNA of organisms in the phylum
      Apicomplexa.
AB  - Organisms in the phylum Apicomplexa appear to have a large extrachromosomal DNA
      which is unrelated to the mitochondrial DNA. Based on the apparent gene content
      of the large (35 kb) extrachromosomal DNA of Plasmodium falciparum, it has been
      suggested that it is a plastid-like DNA, which may be related to the plastid DNA
      of rhodophytes. However, phylogenetic analyses have been inconclusive. It has
      been suggested that this is due to the unusually high A+T content of the
      Plasmodium falciparum large extrachromosomal DNA. To further investigate the
      evolution of the apicomplexan large extrachromosomal DNA, the DNA sequence of the
      organellar ribosomal RNA gene from Toxoplasma gondii, was determined. The
      Toxoplasma gondii rDNA sequence was most similar to the large extrachromosomal
      rDNA of Plasmodium falciparum, but was much less A+T rich. Phylogenetic analyses
      were carried out using the LogDet transformation to minimize the impact of
      nucleotide bias. These studies support the evolutionary relatedness of the
      Toxoplasma gondii rDNA with the large extrachromosomal rDNA of Plasmodium
      falciparum and with the organellar rDNA of another parasite in the phylum
      Apicomplexa, Babesia bovis. These analyses also suggest that the apicomplexan
      large extrachromosomal DNA may be more closely related to the plastid DNA of
      euglenoids than those of rhodophytes.

PMID- 8520582
TI  - Catabolism of tryptophan by Trypanosoma evansi.
AB  - Trypanosoma brucei gambiense, which causes human African trypanosomiasis,
      catabolizes the aromatic amino acid tryptophan via an initial aminotransferase
      catalyzed reaction to form several indole end products, which have been suggested
      to contribute to the pathogenesis of trypanosomiasis. To determine if this same
      pathway exists in T. evansi, the closely related trypanosome pathogen of domestic
      animals, tryptophan catabolism was examined in vitro and in vivo. As is the case
      with human African trypanosomes, T. evansi catabolized tryptophan to form indole
      3-pyruvic acid and smaller amounts of indole-3-acetic acid and indole-3-lactic
      acid. Large concentrations of indole-3-pyruvic acid are excreted in urine of
      trypanosome-infected mice. However, indole-3-ethanol could not be detected in
      incubates of T. evansi or T. b. gambiense, even though the latter species had
      previously been reported to form this neutral metabolite. A new, previously
      unreported tryptophan metabolite was isolated and partially characterized from
      incubates of T. evansi and T. b. gambiense. Although the functional significance
      of tryptophan catabolism to trypanosomatids remains obscure, the pathway is
      quantitatively significant in all species examined thus far.

PMID- 8520583
TI  - Transcription rates and transcript stabilities of macronuclear genes in
      vegetative Euplotes crassus cells.
AB  - In hypotrichous ciliates such as Euplotes crassus genes in the transcriptionally
      active macronucleus are present on individual minichromosomes which occur in gene
      specific copy numbers. This different degree of gene amplification can be
      understood as a means to preset the expression potential of the respective
      genetic information. In addition, the actual steady state transcript amounts are
      governed by the transcription rates and transcript stabilities. To establish the
      relative effects of these three parameters the copy numbers of genes transcribed
      by the three different polymerases were determined. The transcript levels of
      growing or starving vegetative cells were then determined, and nuclear run-on
      assays were performed to determine the transcription rates of the genes in the
      different nutritional states. A weak correlation between the gene copy numbers
      and transcription rates was found. The transcripts of genes synthesized by RNA
      polymerase II exhibited different stabilities upon starvation of the cells,
      compared to the supposedly stable ribosomal 5S and 26S RNA. Refeeding of the
      cells after starvation also resulted in a differential response with respect to
      the accumulation of the transcripts of different genes transcribed by RNA
      polymerase II, which can be interpreted in the context of the gene functions.

PMID- 8520584
TI  - Preliminary characterisation of chlorarachniophyte mitochondrial DNA.
AB  - The division Chlorarachniophyte comprises amoeboflagellate protists with complex
      chloroplasts derived from the endosymbiosis of a eukaryotic alga. Analysis of
      chlorarachniophyte chromosomal DNAs by pulsed-field gel electrophoresis revealed
      an apparently linear 36-kb chromosome that could not be ascribed to either the
      host or endosymbiont nuclei. A single eubacterial-like small subunit ribosomal
      RNA gene is encoded on this chromosome and phylogenetic analyses places this gene
      within a clade of mitochondrial genes from other eukaryotes. High resolution in
      situ hybridization demonstrates that transcripts of the small subunit ribosomal
      RNA gene encoded by the 36-kb chromosome are exclusively located in the
      mitochondria. The 36-kb chromosome thus likely represents a linear mitochondrial
      genome. Small amounts of an apparently dimeric (72 kb) form are also detectable
      in pulsed-field gel electrophoresis.

PMID- 8520585
TI  - Acanthamoeba pearcei n. sp. (Protozoa: Amoebida) from sewage contaminated
      sediments.
AB  - Seabottom sediments from a discontinued Philadelphia-Camden 40-Mile ocean sewage
      disposal site were cultured for cyst-forming free-living amoebae. Barge delivered
      wastes were discharged at the site from 1973 until 1980 when the site was closed.
      One station at the southeast margin of the site was sampled at a depth of
      approximately 50 m, twice in 1978 and once in 1982, 1983 and 1984. Sediment from
      the 1978 collection yielded Acanthamoeba polyphaga, Vahlkampfia sp., and an
      unknown amoeba with stellate endocysts similar to those of A. astronyxis.
      Trophozoites and cysts of the isolate were typical of those described for the
      genus Acanthamoeba. Biochemical tests employing enzyme electrophoresis and
      morphological studies on live and stained specimens showed that the isolate was
      distinct from other well-described species within the family Acanthamoebidae
      Sawyer & Griffin, 1975.

PMID- 8520586
TI  - Antisporozoite antibodies with protective and nonprotective activities: in vitro
      and in vivo correlations using Plasmodium gallinaceum, an avian model.
AB  - A correlation was observed between in vivo and in vitro activity of six
      monoclonal antibodies (mAb) against the major circumsporozoite protein of the
      avian malaria Plasmodium gallinaceum as follows. (1) Two mAb were protective,
      totally abrogating sporozoite infectivity to chicks, its natural host, in vivo;
      they caused 100% inhibition of sporozoite invasion (ISI) in vitro to SL-29
      chicken fibroblasts and intense ISI to cultured chicken macrophages, as well as
      inhibited the exoerythrocytic development of sporozoites taken up by macrophages,
      the initial cell host of P. gallinaceum sporozoites. (2) Two mAb were partially
      protective in that they reduced sporozoite infectivity to chicks, caused partial
      ISI to SL-29 and macrophage cells and partial inhibition to the exoerythrocytic
      development of sporozoites in macrophages in vitro. (3) Two mAb were totally
      inactive in vivo although they both bound to the sporozoite antigens as detected
      by indirect immunofluorescence, western blot, and ELISA; they both failed to
      induce ISI or inhibit the exoerythrocytic development in macrophages. The
      possible participation of macrophages as the initial cell type involved in
      sporozoite destruction in the presence of anti-circumsporozoite antibodies is
      discussed.

PMID- 8520587
TI  - Coordinated flagellar and ciliary beating in the protozoon Tritrichomonas foetus.
AB  - Tritrichomonas foetus is a flagellated protozoon found in urogenital tract of
      cattle. Its free movement in liquid medium is powered by the coordinated movement
      of three flagella projecting towards the anterior region of the cell, and one
      recurrent flagellum that forms a junction with the cell body and ends as a free
      projection in the posterior region of the cell. We have used video microscopy and
      digital image processing to analyze the relationships between the movements of
      these flagella. The anterior flagella beat in a ciliary type pattern displaying
      effective and recovery strokes, while the recurrent flagellum beats in a typical
      flagellar wave form. One of the three anterior flagella has a distinctive pattern
      of beating. It beats straight in its forward direction as opposed to the ample
      beats performed by the others. Frequency measurements obtained from cells
      swimming in a viscous medium shows that the beating frequency of the recurrent
      flagellum is approximate twice the frequency for the three anterior flagella. We
      also observed that the costa and the axostyle do not show any active motion. On
      the contrary, they form a cytoskeletal base for the anchoring and orientation of
      the flagella.

PMID- 8520588
TI  - Evolution of cell adhesion systems: evidence for Arg-Gly-Asp-mediated adhesion in
      the protozoan Neoparamoeba aestuarina.
AB  - Developmental processes in multicellular organisms require structural elements,
      such as adhesion molecules, to stabilize cells at functional positions. In
      vertebrates, a series of extracellular matrix proteins, e.g. fibronectin and
      laminin, are involved in cell adhesion. These proteins contain Arg-Gly-Asp [RGD]
      at their binding sites. Here we show that at concentrations above 2 mM the
      peptide GRGDSPK, comprising the tripeptide RGD (Arg-Gly-Asp), prevents the
      adhesiveness of cells of the marine amoeba Neoparamoeba aestuarina. In addition,
      elevated levels of GRGDSPK cause cells to alter their shapes from those with
      digitiform subpseudopodia to rounded cells with small lobed pseudopodia. These
      cells detach from the substratum. These results are specific for the RGD
      sequence, because incubation in GRGESPK solution at the same concentrations had
      no effect on cell attachment or structure. From these data we suggest that the
      structural adhesion molecules identified in vertebrates show amino acid
      homologies with those found in unicellular protozoa.

PMID- 8520589
TI  - Deciliation induces phosphorylation of a 90-kDa cortical protein in Tetrahymena
      thermophila.
AB  - We have used the anti-phosphoprotein antibody MPM-2 to examine changes in
      phosphorylation of cortical proteins during cilia regeneration in Tetrahymena
      thermophila. Although numerous cortical proteins are phosphorylated in both
      nondeciliated and deciliated cells, deciliation induces a dramatic increase in
      the phosphorylation of a 90-kDa cortical protein. The 90-kDa protein remained
      phosphorylated during cilia regeneration and then gradually became
      dephosphorylated. The 90-kDa protein was phosphorylated and dephosphorylated
      normally in Tetrahymena mutants that assemble short cilia, suggesting that
      achievement of full length is not the signal that triggers dephosphorylation of
      the 90-kDa protein. When initiation of cilia assembly is blocked, the 90-kDa
      protein becomes phosphorylated and remains phosphorylated for an extended period
      of time, suggesting that initiation of cilia elongation triggers eventual
      dephosphorylation of the 90-kDa protein, regardless of how long the cilia
      actually become.

PMID- 8520590
TI  - [Laboratory control of oral anticoagulation].
AB  - BACKGROUND: The authors verified the performance of three different
      thromboplastin preparations, commercially available to Brazilian clinical
      laboratories, on the anticoagulant level monitoring of anti-vitamin K drugs.
      MATERIAL: Thromboplastin preparations included: Labtest, lot n degrees 0301, ISI
      = 1.50; Biolab, lot n degrees 10252, ISI = 1.60; Baxter TPCD, lot n degrees 502A,
      ISI = 2.55; Baxter TPC, lot n degrees 13, ISI = 1.97; Baxter TPS, lot n degrees
      27, ISI = 1.18; and Behring, lot n degrees 505771A, ISI = 1.11. Thirty-one
      outpatients with thromboembolism were evaluated. All patients were taking the
      same dose of anti-vitamin K drugs for at least 10 days. METHODS: Laboratorial
      monitoring has been undertaken by the measurement of Prothrombin Time (TP). A
      standard curve was obtained for each reagent, using a normal plasma pool. Results
      were expressed as PT in seconds, and as prothrombin activity (PA) in percentage,
      according to the standard curve, and also as the International Normalized Ratio
      (INR), calculated using the International Sensitivity Index (ISI) provided by
      each reagent producer. RESULTS: There was some discrepancy among results obtained
      with different reagents, when these results were expressed as PA (p < 0.01), but
      this effect was minimized when they were expressed as INR. CONCLUSIONS: This fact
      confirms that results of PT, performed in order to control the action of anti
      vitamin K drugs, must be reported as INR to assure reproducibility among tests
      performed using different thromboplastin reagents, with different ISI.

PMID- 8520591
TI  - [Stimulus of the hypophyseal-adrenocortical axis with corticotropin releasing
      hormone (CRH) in acquired immunodeficiency syndrome. Evidence for activation of
      the immune-neuroendocrine system].
AB  - Ten-20% of patients with AIDS may present clinical evidence of primary or
      secondary adrenal insufficiency. PURPOSE--To evaluate the hypothalamic-pituitary
      adrenocortical axis (HPAA) with CRH in patients with AIDS. METHODS--We studied 20
      patients with AIDS and 17 normal subjects (NS) with exogenous ACTH (cosyntropin,
      250 micrograms IV bolus) followed one week later by ovine corticotropin releasing
      hormone (oCRH 1 microgram/kg BW IV bolus). Basal and 60' cortisol (micrograms/dL)
      were determined in the former whereas ACTH (pg/mL) and cortisol were measured
      every 15-30' for 2 hours in the latter. RESULTS--Basal and peak values (mean +/-
      SD) of ACTH and cortisol for both tests were: cosyntropin test (AIDS x NS): basal
      cortisol 22.5 +/- 7.1 x 10.6 +/- 3.6 (p < 0.01), peak 36.0 +/- 12.8 x 28.3 +/-
      7.6 (p < 0.05); oCRH test: basal ACTH 42.2 +/- 33.5 x 28.9 +/- 12.7 (NS), peak
      104.7 +/- 62.2 x 59.3 +/- 17.6 (p < 0.05); basal cortisol 19.7 +/- 9.0 x 10.1 +/-
      3.4 (p < 0.01), peak 27.5 +/- 8.9 x 18.3 +/- 5.1 (p < 0.05). CONCLUSION--AIDS
      patients had elevated basal and CRH stimulated ACTH levels and an intact
      glucocorticoid pathway with elevated basal and peak cortisol levels to both
      stimulation tests. This situation is probably due to the stressful disease
      condition, where lymphokines may play a role activating the hypothalamic
      pituitary axis.

PMID- 8520592
TI  - [Standardization of immunofixation technique for the detection and identification
      of serum paraproteins].
AB  - Diagnosis and follow up of paraproteinaemias require identification and typing of
      paraproteins. Immunoelectrophoresis is the most commonly used method, though a
      lengthy one and with low sensitivity. Immunofixation is more sensitive, faster
      and of easier interpretation, specially when monoclonal proteins are present in
      low concentration in the serum and/or urine. Immunofixation includes two steps.
      The first is electrophoresis; the second is immunofixation of the separated
      antigen by use of antiserum. The latter step is accomplished by layering the
      antiserum over the agarose gel immediately after electrophoretic separation of
      the proteins resulting in antigen/antibody precipitation. PURPOSE--The objective
      of this study is to standardize the technique of immunofixation and compare it to
      immunoelectrophoresis. METHOD--The serum of 28 patients (25 with multiple myeloma
      and 3 with polyclonal hypergammaglobulinaemia) was analysed and compared to 6
      normal subjects. All were submitted to electrophoresis on agarose gel,
      immunoelectrophoresis and immunofixation. RESULTS--Dilution of the serum to
      produce a concentration suitable for immunofixation is critical. In our study the
      correct paraprotein concentration was 28 to 35 g/dl. Both methods detected and
      identified the paraprotein in 21 (84%) of the samples and in 2 (8%) it was not
      detected at all. In two of the samples, only immunofixation was able to detect
      and identify the paraprotein. There was not any monoclonal band observed either
      through the electrophoresis or immunoelectrophoresis that was not detected by the
      immunofixation. CONCLUSION--These results show that immunofixation is more
      sensitive than immunoelectrophoresis and therefore should be incorporated into
      diagnosis routine.

PMID- 8520593
TI  - [Ureteral colic and emotional stress].
AB  - Clinical practice often shows evidences of organic patterns originated from
      conflicting psychosocial configurations and excessively stressing contexts of
      life. The ureteral colic, a frequent and severe morbid entity owing to the
      lancinating, incapacitating and recurrent pain, however has been kept far from
      studies which corroborate this perception. MATERIAL AND METHOD: A kind of Case
      and Control research in 40 patients with an ureteral colic history, has
      quantified, through the use of the Holmes and Rahe Inventory, the stressing
      factors in periods of time preceeding the ureteral colic patterns, in comparison
      to normal controls. RESULTS: The results show a statistically significant
      difference in favor of cases in a 14 day period, through the stratifying
      analysis, an individual score higher or equal to 150 points (p = 0.00227949).
      There was no statistically significant difference in a 12 month period (p =
      0.29990307), which makes evident the decreasing of the sensibility concerning the
      method to this period. CONCLUSION: This result corroborates the evidence of the
      influence of the emotional stress preceding, in a 14 day studied interval, the
      unchaining of these crises in predisposed people.

PMID- 8520594
TI  - [Risk factors for uterine cervix condyloma in sexually active adolescent women].
AB  - Factors most commonly associated with cervical cancer are early start of sexual
      activity and papillomavirus infection. PURPOSE--Studying risk factors for
      cervical condyloma in sexually active adolescents in the region of Campinas, SP,
      Brazil. METHOD--131 adolescents with condyloma and 131 without disease,
      controlled by age and pregnancy state, were compared according to social
      demographical, sexual-behavioral and gynecological/obstetrical variables.
      Relative risk evaluation was performed for each variable and multivariate
      analysis with logistic regression was made to determine confunding factors.
      RESULTS--Tobacco smoking and nulliparity were identified as independent risk
      factors for cervical condyloma in this population. More than two sexual partners
      and low level of schooling were identified as risk factors in the univariate
      analysis, however, these factors were highly correlated with tobacco smoking and
      parity, respectively. All other variables were similar in both groups. CONCLUSION
      -Although tobacco smoking and nulliparity were identified as risk factors for
      cervical condyloma, it is very difficult to characterize a sexually active
      adolescent group without risk for infection.

PMID- 8520595
TI  - [Preservation of gonadotrophic function and pregnancy in Sheehan's syndrome: a
      case report and review of the literature].
AB  - Pregnancy occurring in patient with Sheehan's syndrome is seldom described. It
      depends on the preservation of LH and FSH secretion after the pituitary apoplexy
      event. PURPOSE--To report a patient with Sheehan's syndrome who became pregnant
      twice after the pituitary apoplexy episode and to discuss the maintenance of
      gonadotrophic function. METHOD--Clinical aspects are described and the pituitary
      reserve evaluation was performed as well as a computerized tomography and a
      magnetic resonance imaging of the brain. RESULTS--Gonadotrophic and thyrotrophic
      function were preserved and the neuroradiologic evaluation disclosed an empty
      sella turcica preservation of the posterior lobe of the hypophysis. CONCLUSION--A
      patient with Sheehan's syndrome is reported in whom the LH and FSH pituitary
      secretion was preserved allowing normal pregnancy twice after the pituitary
      apoplexy.

PMID- 8520596
TI  - HLA A/B recombination in a white woman with the S-s-phenotype of the MNS system.
AB  - In cases of disputed parentage, the possibility of simultaneous occurrence of
      rare events in the population must be considered. PURPOSE--To report a case in
      which HLA-A/B recombination and homozygosity of a silent allele, typical of
      Negroes, in an individual apparently without this miscegenation were coexistent.
      METHODS--Alleged father, mother and dizygotic twin children were racially
      classified according to their apparent somatic characters. Blood group genetic
      markers of ABO, Rh, MNS, Kell, Duffy, HLA-A, -B systems were phenotyped; mother's
      HLA genotyping was performed by her parents test. RESULTS--The phenotype of the
      White mother, in the MNS system, was M+; N-; S-; s-. Alleged father and both
      twins were phenotipically compatible. The assumed maternity relating to both
      children was possible if mother presented an HLA-A/B recombination. CONCLUSION-
      In miscegenated populations, the breakup between ethnical appearance and blood
      group markers is foreseeable. Allele/haplotypic frequencies of these populations
      should be estimated. Casuistically, the association of events with low frequency
      in the population can be the cause of apparent exclusions of parentage.

PMID- 8520597
TI  - [Serological evaluation for human immunodeficiency virus (HIV) and for hepatitis
      B (HBV) among candidates who have passed the admission tests at a hospital
      institution in Sao Paulo].
AB  - Health professionals (HP) are frequently exposed to accidents with materials
      contaminated with blood and/or body fluids, thus representing a population at
      risk for the acquisition of human immunodeficiency virus (HIV) and hepatitis B
      virus (HBV). PURPOSE--To determine the prevalence of HIV and HBV infection among
      HP admitted to the University Hospital, Faculty of Medicine, University of Sao
      Paulo (UH-FMUSP), and to identify the possible sources of contamination. METHODS-
      A total of 345 HP who sequentially passed the hiring examination at UH-FMUSP from
      March 1 to June 23 1993 were evaluated and compared to 2521 blood donors using
      serologic tests for the detection of AgHBs and total anti-HBc of HBV. The ELISA
      method was also used for HIV-1, with subsequent confirmation by Western blot.
      Questionnaires were distributed to the HP for the identification of possible
      sources of contamination. RESULTS--Positivity to HIV-1 was 0.48% for HP and 0.23%
      for blood donors, and positivity to HBV was 8.89% and 6.17%, respectively.
      CONCLUSION--There was no statistically significant difference in the results of
      the serologic tests for HIV and HBV detection between the two groups, even taking
      into consideration the different professions of those who work in the health area
      and their potential exposure to blood and secretion.

PMID- 8520598
TI  - [Cephalosporins: 4 generations of structural evolution].

PMID- 8520599
TI  - [Homologous transplantation of a limb (compound tissue): perspective for the
      future].

PMID- 8520600
TI  - [Advances in the treatment of human immunodeficiency virus (HIV) infection].

PMID- 8520601
TI  - [Smoking: the social challenge].

PMID- 8520602
TI  - [Analysis of the factors associated with recurrence of post-thyroidectomy
      goiter].
AB  - The factors associated with post-thyroidectomy goiter recurrence in benign
      thyroid disease are not clearly defined, especially prophylactic thyroxine
      treatment. PURPOSE--To determine the prevalence, characteristics and associated
      factors of recurrence of goiter post-thyroidectomy in patients submitted to
      surgery for benign disease. METHODS--Sixty-six patients, 53 female and 13 male
      (mean age = 51 yrs., range 20-82 yrs.), previously (5.6 +/- 6.1 yrs.) submitted
      to thyroidectomy (lobectomy, n = 50; nodulectomy, n = 5; subtotal thyroidectomy,
      n = 11) for benign thyroid disease were included. Measurements of T3, T4, TSH,
      thyroid microsomal autoantibody titers and thyroid ultrasonography were performed
      at the time of the study. Recurrence of goiter post-thyroidectomy was defined on
      ultrasonography as the presence of residual thyroid volume > 20mL and/or new
      nodules > 0.5mL not detected at surgery. RESULTS--Seven patients (10%) developed
      recurrence of goiter. The post-operative follow-up period was longer in the
      recurrence group and there was no difference between the two groups as to age,
      sex, familial history of thyropathy and preoperative goiter diagnosis. In
      multiple regression analysis only the following post-operative period was
      significantly associated to goiter recurrence (beta = 0.02; R2 = 0.16; p < 0.05)
      and influenced the goiter recurrence rate by 14%. Familial history of thyropathy,
      thyroxine treatment in non-supressible doses after thyroidectomy and seric T4 and
      TSH levels did not influence the recurrence. CONCLUSION--Recurrence of goiter
      post-thyroidectomy occurs in a small number of patients and is related to longer
      post-operative follow-up time. Thyroxine treatment in non-supressible doses after
      surgery is not related to goiter recurrence prevention.

PMID- 8520603
TI  - [Alphafetoprotein in hepatic tumours and benign liver diseases].
AB  - AFP is an oncofetal protein found in increased levels in hepatocellular
      carcinoma, liver metastasis and other benign liver diseases. PURPOSE--To know the
      behaviour of this protein in each of these clinical situations would undoubtedly
      help us to discriminate between hepatocellular carcinoma and benign diseases.
      PATIENTS--A hundred forty nine patients were divided into 4 groups: 1. acute
      hepatitis (AH) n = 24, 2. chronic liver disease, viral or alcoholic (CLD) n = 81,
      3. hepatic metastasis (HM) n = 29, 4. hepatocellular carcinoma (HCC) n = 15. AFP
      assays were done by ELISA (Abbott Diagnostica, ref. value: 15ng/mL). RESULTS--The
      results observed were as follows: AFP < 15ng/mL: AH 75%, CLD 86.4%, HM 79.3%, HCC
      6.6%, AFP > 15 e < 100ng/mL: AH 25%, CLD 8.6%, HM 20.6%, HCC 20%, AFP > 100ng/mL:
      AH zero, CLD 4.9%, HM zero, HCC 49%. It is clear that depending on the cut off
      level, there is a decrease of sensibility which is paralleled by an increase in
      specificity. CONCLUSIONS--AFP levels are increased in benign liver diseases (AH,
      CLD) and HM, how ever levels above 100ng/mL occur much more frequently in HCC. In
      our sample, 93.3% of the HCC showed high levels of AFP, probably because most of
      the patients had advanced clinical stages of the disease.

PMID- 8520604
TI  - [Critical analysis of the clinical and surgical importance of the variations in
      the origin of the sinoatrial node artery of the human heart].
AB  - There are several clinical controversies derived from the discrepancy on the
      description and relations of the coronary arteries in human hearts of either sex
      and in different races. OBJECTIVE--To study the clinical and surgical importance
      of the variations of the origin of the artery of the sinoatrial node in hearts of
      human individuals. MATERIAL AND METHOD--Normal hearts of cadavers of 100
      individuals (31 females and 69 males), belonging to 24 Caucasians (whites) and 36
      non-Caucasians (Negroes and Mulattoes), whose age varied ranged from 7 to 80
      years, were studied. The coronary arteries were injected with gelatin mixed to a
      radiopaque substance (Cylatrast) and a red or blue pigment. RESULTS AND
      CONCLUSIONS--1) The artery of the sinoatrial node was originated more frequently
      from the right coronary artery (58%) than from the left. 2) When originated from
      the left coronary artery the artery of the sinoatrial node was more frequently a
      branch of the circumflex artery (30%) than from the trunk of the artery (12%). 3)
      No sexual or racial factor influenced the anatomical variations. 4) The most
      frequent arteries originating the artery of the sinoatrial node were the right
      anterior medial atrial artery and the left anterior medial atrial artery. 5) No
      cases of blood supply to the sinoatrial node were found originating neither from
      other arteries than the coronary arteries nor from both coronary arteries. 6) The
      distribution of the coronary arteries allows to understand the possible ischemic
      etiology of the sinusal node syndrome and permits to the surgeon a safe approach
      to cardiac disease.

PMID- 8520605
TI  - Public service deficiencies and Aedes aegypti breeding sites in Venezuela.
AB  - The 1992 study reported here assessed relationships between potable water supply
      and trash collection practices and the prevalence of dengue vector mosquito
      (Aedes aegypti) breeding sites in 30 towns located along the north coast of
      Venezuela. Within each study town, 100 homes were chosen. At each of these homes
      the number of water-bearing containers and containers harboring A. aegypti were
      determined and interviews were conducted to obtain information about the local
      water supply, trash collection services, and excreta disposal. In general, A.
      aegypti breeding indexes were high: 55% of the residences were found to harbor A.
      aegypti immature forms; there was an average of 118 breeding sites per 100
      residences; and 24% of the water-bearing receptacles were observed to contain the
      mosquito. The statistical method of principal component analysis was employed to
      rank the 30 towns in terms of variables describing public service deficiencies,
      and correlations existing between the variables studied were determined. Direct
      correlations were found between two water supply variables (frequency and
      duration of water supply interruptions), between the excreta disposal and trash
      collection variables, between the duration of water supply interruptions and the
      Aedes breeding indexes, and between the duration of water supply interruptions
      and the mean number of A. aegypti breeding sites found in water storage
      containers. Overall, the towns with the poorest services were found to have the
      highest breeding indexes and the greatest numbers of water storage containers
      harboring the mosquito. It is concluded that public service (water supply and
      waste disposal) deficiencies were largely responsible for A. aegypti propagation
      in the study towns. Accordingly, it is recommended that local programs be
      implemented for recycling containers, constructing water storage tanks that
      cannot harbor Aedes larvae, and conducting health education and community
      participation campaigns directed against the mosquito.

PMID- 8520606
TI  - Comparative study of safety and efficacy of IUD insertions by physicians and
      nursing personnel in Brazil.
AB  - To assess whether trained nursing personnel could provide IUD services as safely
      and effectively as physicians in Brazil, an experimental study was conducted at
      the main clinic of the Center for Research on Integrated Maternal and Child Care
      in Rio de Janeiro. From November 1984 through April 1986, a total of 1,711 women
      who requested IUD insertion at the clinic were randomly assigned to have a Copper
      T 200 IUD inserted by one of the clinic's 11 physicians or 13 nurses. All of the
      physicians and nursing staff members who provided these services had taken the
      Center's standard clinical family planning training course. Of 860 insertions
      attempted by the physicians and nurses, 1.3% and 3.3%, respectively, were
      unsuccessful. Statistically, this difference was very significant (P < 0.01).
      Also, mainly because the cervix was small and undilated, nulliparous women had a
      relatively high insertion failure rate of 8.0%, as compared to 1.5% for
      primiparas and 1.0% for multiparas. The overall rate of complications at
      insertion was 1.8%, these complications including diaphoresis, vomiting, syncope,
      cervical laceration, and one case of perforation of the uterus; no significant
      difference was found between the complication rates for insertions performed by
      physicians as compared to nurses. However, 9.0% of the study subjects reported
      severe pain during IUD insertion, with significantly higher percentages reporting
      pain if the IUD was inserted by a physician, or if the subject was nulliparous,
      had preinsertion symptoms, or had a history of pelvic inflammatory disease (PID)
      or sexually transmitted disease (STD). It was also found that the nurses had a
      dramatically high insertion failure rate (11.6%) with nulliparous subjects, while
      the physicians' failure rate with such subjects was a significantly lower 3.4%.
      No significant difference was found in the groups served by nurses and physicians
      with regard to postinsertion complaints or termination of use within 12 months of
      insertion. These findings suggest that future training, besides preparing nursing
      personnel in IUD insertion, should emphasize preparation in taking the client's
      medical history and diagnosing existing medical symptoms that could be associated
      with IUD insertion complications. In addition, if a nulliparous woman requests an
      insertion, it should be performed by a physician or more experienced nursing
      staff member with close medical supervision. Because of high rates of reported
      pain at insertion, such women, as well as those with medical symptoms associated
      IUD insertion complications and those with a history of PID or STD, should be
      considered candidates for extra care and counseling.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8520607
TI  - Trends in relative mortality from cerebrovascular diseases in Brazilian state
      capitals, 1950-1988.
AB  - This article seeks to describe trends in relative mortality from cerebrovascular
      diseases (CVDs) in Brazilian state capitals from 1950 through 1988. Absolute
      numbers of deaths from all causes; from CVDs; and from ill-defined signs,
      symptoms, and afflictions were obtained from official Brazilian mortality
      statistics. In calculating relative CVD mortality, deaths from ill-defined signs,
      symptoms, and afflictions were excluded. The collected data permitted calculation
      of relative CVD mortality in most state capitals for 1950, 1955, 1960, 1961-1965,
      1966-1970, 1971-1975, 1977-1980, 1981-1985, and 1986-1988. During the study
      period CVD mortality was found to play an increasing role in overall mortality in
      all the state capitals. Regional grouping of data showed greater relative CVD
      mortality in the South and Southwest Regions toward the start of the study
      period. However, over the course of this period the part that CVD mortality
      played in overall mortality grew most rapidly in the less-developed North,
      Northeast, and Center-West Regions. In general, relative CVD mortality data in
      nearly all the state capitals demonstrate the attention that needs to be devoted
      to CVDs within the context of adult public health. In particular, there is a
      clear need to greatly strengthen and improve the marginal existing programs for
      detection and control of hypertension and diabetes in Brazil. This should be done
      by assessing international experience with programs of this type and adapting
      that experience to Brazilian conditions. Beyond that, it will be important to
      support health promotion and protection efforts that can deal with risk factors
      and secure prevention through lifestyle modification--something that can provide
      benefits in dealing not only with CVDs but also with diabetes, obesity, and
      certain neoplasias.

PMID- 8520608
TI  - Restriction fragment length polymorphism (RFLP) analysis and tuberculosis
      epidemiology.
AB  - In order to study polymorphisms of the DNA insertion sequence 6110 (IS6110) in
      Mycobacterium tuberculosis strains isolated from Colombian patients, together
      with resistance to antituberculous medications in the Department of Quindio,
      Colombia, a prospective study was conducted using a consecutive sample of 59
      patients with symptomatic pulmonary tuberculosis whose cases had been confirmed
      by bacilloscopy, both with and without a history of treatment. The patients, who
      were participating in the Tuberculosis Control Program of the Regional Health
      Institute of Quindio in Armenia, included all individuals attending local health
      centers and hospitals between March and July 1993 who were referred to the
      regional institute. Sputum specimens from each patient were cultured and
      subjected to drug sensitivity tests. Subsequently, restriction fragment length
      polymorphisms (RFLP) of IS6110 from 27 patients were analyzed. The patients'
      treatment histories were used to classify their cases according to WHO criteria.
      Forty-five cultures were found positive, 44 for M. tuberculosis and 1 for M.
      africanum. Initial drug resistance was observed in 4 of 42 new cases, or 9.5%
      (95% CI: 0.6, 18), 2 showing resistance to isoniazid (INH) and 2 to isoniazid
      plus streptomycin (INH-SM). Acquired resistance was observed in 2 of the 3
      chronic cases and relapses, the bacteria being resistant to isoniazid,
      rifampicin, and streptomycin (INH-RM-SM) in one case and to isoniazid,
      ethambutol, rifampicin, and streptomycin (INH-EMB-RM-SM) in the other. In those
      27 strains subjected to RFLP analysis, the number of copies of IS6110 ranged from
      6 to 17. Similarity coefficients revealed five distinct groups of strains.
      Overall, the RFLP analysis permitted most of the strains to be distinguished from
      one another, implying that the polymorphisms involved are sufficient to permit
      effective employment of this technique, which appears to have considerable
      potential for use in epidemiologic studies and in work designed to provide a
      basis for tuberculosis control program decision-making.

PMID- 8520609
TI  - Correct case management of childhood diarrhea: a survey of nine state capitals in
      northeast Brazil.
AB  - The National Program for Maternal and Child Health (COSMI) of the Ministry of
      Health (MOH) of Brazil conducted a survey in nine state capitals from 29 March to
      30 April 1993 to assess how well health facilities were managing diarrhea cases
      in patients under 5 years of age. One of seven PAHO/WHO health facility surveys
      performed in Latin America and the Caribbean in 1992-1993, the Brazilian survey
      took place in the Northeast Region where most diarrheal morbidity and mortality
      occur. Like the other six surveys, it used a new PAHO/WHO methodology designed to
      collect data on certain principal indicators through observation, interviews, and
      review of clinical records. Overall, 475 cases of patients with diarrhea were
      observed in 192 facilities, and 463 health workers and 474 caretakers were
      interviewed. The results indicated that few diarrhea patients received care that
      strictly followed the PAHO/WHO/Ministry of Health treatment guidelines. In terms
      of these guidelines, the correct procedure was used to assess the patient's
      hydration status only 8% of the time, and only 1% of the health workers provided
      correct advice to the caretaker on prevention and home care aspects of diarrheal
      diseases. The procedure used to rehydrate patients with oral rehydration salts
      (ORS) was correct in only 6% of the cases. Of those patients with bloody stools,
      24% were treated appropriately with antibiotics. Besides collecting information
      on correct case management, the survey provided a basis for developing two-year
      operational plans of action in each of the nine participating states to
      strengthen efforts directed at controlling and preventing diarrheal diseases,
      including cholera.

PMID- 8520610
TI  - Periconceptional folic acid and neural tube defects: public health issues.
AB  - This review examines evidence linking periconceptional folic acid intake to
      neural tube defects (NTDs) and related public health issues in the United States
      and developing countries. Sources of information were identified through on-line
      searches (Medline, UCAT-University of Connecticut) and by contacting researchers
      in the field. The distribution of NTDs varies across regions. Recurrent NTDs can
      be prevented with high-dosage folic acid supplementation during periconception,
      but it is not clear if such a protective effect can be achieved with lower
      dosages or in low-NTD-risk populations. Overall, it appears that women with a
      previous NTD pregnancy should receive folic acid supplementation during
      periconception under medical guidance. Dietary counseling regarding foods rich in
      folate should be given to all women of childbearing age. However, primary
      prevention of NTDs through widespread food fortification with folic acid seems
      unwarranted in both the United States and developing countries due to the low
      prevalence of NTDs relative to other problems and a potentially unfavorable
      benefit/risk ratio.

PMID- 8520611
TI  - Prospects and challenges for health in the Americas.

PMID- 8520612
TI  - Healthy Municipios in Latin America.

PMID- 8520613
TI  - PAHO measles reference laboratory network.

PMID- 8520614
TI  - Irradiation for the prevention of foodborne diseases.

PMID- 8520615
TI  - Bellagio statement on tobacco and sustainable development.

PMID- 8520616
TI  - Biotechnology research training grants program.

PMID- 8520617
TI  - Strategies and causes of reduced infant and young child diarrheal disease
      mortality in Cuba, 1962-1993.

PMID- 8520618
TI  - Conservative management options for cervical pregnancy; case reports and
      literature review.
AB  - OBJECTIVE: To describe three cases of cervical pregnancy treated successfully
      with different conservative methods and review the literature on conservative
      treatment of cervical pregnancy over the last 30 years. METHODS: Three patients
      treated conservatively for cervical pregnancy are reported. The literature
      regarding the conservative management of cervical pregnancy since 1965 was
      compiled using a MEDLINE search for articles published since 1980 and by
      reviewing the reference lists of published manuscripts. RESULTS: Three cases of
      cervical pregnancy were successfully treated using methotrexate with leucovorin
      rescue, methotrexate without leucovorin rescue, and curettage after angiographic
      embolization of the right hypogastric and left uterine arteries. Review of
      conservatively managed cases of cervical pregnancy since 1965 indicates that
      medical management with methotrexate and preoperative angiographic embolization
      of the uterine blood supply, when appropriate, results in successful treatment
      without the need for transfusion. CONCLUSIONS: Clinical suspicion of cervical
      pregnancy early in gestation with preoperative diagnosis may safely allow
      conservative treatment. Different clinical scenarios may preclude or limit which
      conservative management options are best for each case.

PMID- 8520619
TI  - Nonbacterial pyospermia: a consequence of clomiphene citrate therapy.
AB  - OBJECTIVE: Since the development of nonbacterial pyospermia in previously
      nonpyospermic men treated with clomiphene citrate (CC) has been observed, and
      nonbacterial prostatitis has been after antiestrogen treatment in an animal
      model, we sought characterize the occurrence of nonbacterial pyospermia in men
      treated with CC. PATIENTS AND METHODS: Forty-two nonpyospermic men with low serum
      testosterone levels treated with 25 mg CC/day were retrospectively compared to 27
      untreated nonpyospermic men referred for infertility evaluation. RESULTS:
      Spontaneous nonbacterial pyospermia developed in CC-treated men [14.3%] at rate
      nearly twice that observed in controls [7.4%]. Serum testosterone increased in CC
      treated men, both pyospermic and nonpyospermic. However, only CC-treated,
      nonpyospermic men demonstrated improvement in semen characteristics. CC-treated
      men who developed pyospermia were older than nonpyospermic men [pyospermic, 41.7
      +/- 8.1 years; nonpyospermic, 35.6 +/- 4.9 years-P < .01). Men over 35 years of
      age were over six times as likely to develop pyospermia as men under 35 years of
      age (P < .05). Eight nonpyospermic, CC-treated men (8/36, 22.2%) have contributed
      to pregnancies leading to live births, whereas no pyospermic man has done so.
      CONCLUSION: These findings support an association between a nonbacterial
      inflammatory response of the human male reproductive tract and CC treatment. This
      pyospermia may occur without significant deterioration of semen characteristics
      and with an appropriate response to treatment in terms of serum testosterone
      level. Men over the age of 35 are statistically more likely to develop pyospermia
      with this therapy. Our results suggest that clomiphene citrate-associated
      pyospermia has a negative effect on male fertility.

PMID- 8520620
TI  - Effect on sperm-immobilizing antibodies on the spontaneous and calcium-ionophore
      (A23187)-induced acrosome reaction.
AB  - OBJECTIVE: To study the effect of sperm-immobilizing antibodies on spontaneous
      and A23187-induced acrosome reactions. MATERIAL AND METHODS: Swim-up spermatozoa
      obtained from a fertile donor were incubated with 16 sera containing sperm
      immobilizing antibodies obtained from infertile women and 3 control sera obtained
      from healthy females. The acrosome loss, either occurring spontaneously or
      induced by 10-microM A23181, were examined by staining sperm with Pisum sativum
      agglutinin labeled with fluorescein isothiocyanate. RESULTS: The incidence of the
      spontaneous acrosome reaction of spermatozoa incubated with anti-sperm antibodies
      (6.25 +/- 1.4%) was significantly (P < .001) lower than that of the spermatozoa
      incubated with control sera (12 +/- 0.8%). The incidence of A23187-induced and
      inducible (incidence of induced minus spontaneous) acrosome reactions of
      spermatozoa incubated with sera-positive for sperm antibodies (10.4 +/- 1.3% and
      4.2 +/- 1.5%) was also significantly lower (P < .001) than that of spermatozoa
      incubated with control sera (30.7 +/- 0.5% and 18.7 +/- 1.2%). CONCLUSION: Sperm
      immobilizing antibodies interfere with fertilization by inhibiting the acrosome
      reaction.

PMID- 8520621
TI  - Relationship between serum estradiol concentration and IGF-I, IGF-II and IGF
      binding proteins in patients with premature ovarian failure on short-term
      estradiol therapy.
AB  - OBJECTIVE: Insulin-like growth factors (IGFs) exert stimulatory effects on
      follicular growth and development, and early embryogenesis. In view of this, we
      studied the effect of short-term estradiol treatment, as used in preparing the
      uterus for embryo implantation, on the serum concentrations of IGFs and their
      binding proteins (IGFBP) in patients with premature ovarian failure (POF).
      PATIENTS AND METHODS: Twenty-four patients with POF, enrolled in an assisted
      reproduction program, were treated with increasing doses of estradiol up to 8 mg
      daily for 6 weeks. Blood was sampled for measurement of serum estradiol, IGF-I,
      IGF-II, and IGFBP 1, 2 and 3 at various times during estradiol treatment.
      RESULTS: There was no significant correlation between serum estradiol
      concentrations and the serum concentrations of IGF-I and IGF-II. As expected, IGF
      I and IGF-II concentrations in serum correlated positively with the serum
      concentration of IGFBP-3, the major IGF-binding protein in serum. CONCLUSION: The
      results of this study suggest that estradiol therapy as used to prepare the
      uterus for implantation has no significant effect on serum IGF-I and IGF-II
      concentrations, and therefore probably does not influence, via an IGF-mediated
      mechanism, the success of implantation and early embryonic development.

PMID- 8520622
TI  - A system for simultaneous bilateral tubal cannulation.
AB  - OBJECTIVE: The efficacy of a new system for simultaneous bilateral tubal
      cannulation under tactile impression was evaluated. METHODS: Two radiologically
      detectable selective salpingography catheters (Bard Gynecology and Urology,
      Covington, GA) were glued back to back in a "T" configuration similar to an
      intrauterine device. A sliding plastic sleeve contained the straightened
      catheters and the uterus was cannulated under tactile impression. The sleeve was
      then withdrawn and the catheters opened within the uterine cavity and wedged into
      the right and left tubal ostia simultaneously. Selective injection of water
      soluble radiologic contrast material into the tubes resulted in selective
      salpingography and determined successful tubal cannulation. Withdrawal of the
      catheters back into the sleeve allowed injection of contrast material into the
      uterine cavity. PATIENTS: The system was evaluated in 14 consenting patients
      scheduled for hysterosalpingogram during infertility evaluation. RESULTS:
      Bilateral selective salpingography was achieved successfully under tactile
      impression in 12/14 (86%) patients. In two patients with either distorted or very
      small uterine cavity, the catheter tips embedded into the lateral uterine walls
      and did not selectively cannulate the tubal ostia. Reapplication of the system
      under fluoroscopy allowed bilateral selective salpingography of these two
      patients. CONCLUSION: Simultaneous bilateral selective salpingography eliminated
      the need for cervical cannula, significantly reduced fluoroscopy time to seconds,
      and demonstrated that tactile cannulation is successful in normal uteri.
      Application of this system for simultaneous tubal cannulation is identical to
      intratubal uterine device insertion, a procedure familiar to all gynecologists.
      Therefore, this catheter system may further contribute to simplification of
      transcervical access into the fallopian tubes for diagnosis and treatment.

PMID- 8520623
TI  - Norethindrone--a review of therapeutic applications.
AB  - Norethindrone is utilized for numerous noncontraceptive therapies, especially
      during the menopause. Through an analysis of the literature we have described the
      pharmacological profile of norethindrone and the potential therapeutic
      implications of low-dose therapies, with an emphasis on endometrial pathology,
      climacteric symptoms, lipid metabolism, and bone density.

PMID- 8520624
TI  - Membrane protein structure: the contribution and potential of novel solid state
      NMR approaches.
AB  - Alternative methods for describing molecular detail for large integral membrane
      proteins are required in the absence of routine crystallographic approaches.
      Novel solid state NMR methods, devised for the study of large molecular
      assemblies, are now finding applications in biological systems, including
      integral membrane proteins. Wild-type and genetically engineered proteins can be
      investigated and detailed information about side chains, prosthetic groups,
      ligands (e.g. drugs) and binding sites can be deduced. The molecular structure
      and dynamics of selected parts of the proteins are accessible by a range of
      different solid state NMR approaches. Inter- and intra-atomic distances can be
      determined rather accurately (within angstroms) and the orientation of molecular
      bonds (within 2 degrees) can be measured in ideal cases. Here, a brief
      description of the methods is given and then some specific examples described
      with an indication of the future potential for the approaches in studying
      membrane proteins. It is anticipated that this emerging NMR methodology will be
      more widely used in the future, not only for resolving local structure, but also
      for more expansive descriptions of membrane protein structure at atomic
      resolution.

PMID- 8520625
TI  - Do band 3 protein conformational changes mediate shape changes of human
      erythrocytes?
AB  - The bilayer-couple model predicts a reversible membrane crenation for an
      increasing ratio of external to internal monolayer area. This was comprehensively
      proven. However, individual erythrocytes may undergo dramatic shape changes
      within seconds when the suspension medium is changed. In contrast, under
      physiological conditions with no addition of membrane active compounds, active
      phospholipid translocation and passive flip-flops are comparatively slow. We
      propose that conformational changes of the anion-exchange protein, band 3, may
      rapidly alter the monolayer area ratio. Band 3 occupies about 10% of the total
      membrane area of human erythrocytes. Under physiological conditions, its
      conformers are asymmetrically distributed with about 90% of the transport sites
      facing the cytoplasm. This distribution is altered when external conformations
      are recruited by changing the transmembranous Cl- gradient, the external pH, or
      by the application of inhibitors. In experiments, recruitment by low ionic
      strength caused a rapid, temporary formation of echinocytes. This suspension
      effect could also be found at high ionic concentrations, when Cl- was replaced by
      SO4(2-). Inhibitors known to recruit the external band 3 conformation, like DIDS,
      SITS and flufenamic acid, are echinocytogenic. For inhibitors not recruiting a
      certain conformation, e.g. phenylglyoxal and niflumic acid, no shape effect was
      found. Since band 3 ensures a fast equilibrium of internal and external anions
      these ions are usually distributed according to the transmembrane potential
      (TMP). In the literature, a correlation of TMP and band 3 conformation, as well
      as a correlation of TMP and red cell shape, is described. In the proposed model,
      low external Cl- concentrations, inhibitors, or a negative TMP may recruit the
      transport sit outwards.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520626
TI  - The specificity of glycolipid-preferredoxin interaction: requirements for
      membrane binding.
AB  - Preferredoxin (prefd) is a precursor protein that is imported into chloroplasts.
      Monolayer experiments have shown that prefd has a high affinity for
      monogalactosyldiglyceride (MGaIDG) isolated from chloroplasts, which contains
      polyunsaturated fatty acid constituents and is therefore in a liquid-expanded
      state, but has been found to interact also with MGaIDG with long-chain saturated
      fatty acids, which exist in a gel state. For an optimal interaction, the fatty
      acid chain length and the extent of unsaturation are also important parameters,
      whereas the conformation of the sugar moiety, the sugar-glycerol or glycerol
      hydrocarbon chain linkages are of little influence on the pressure changes
      measured in monomolecular layers. Conversely, steric hindrance of a methyl group
      at position 3 of the sugar largely inhibits the interaction. Quantification of
      the interaction with radiolabelled prefd shows that only a small part of the
      molecule is able to penetrate MGaIDG in the gel state, whereas a nearly four
      times larger part is able to penetrate MGaIDG isolated from chloroplasts. It is
      likely that interactions of the transit sequence of prefd with the glycolytic
      head group MGaIDG are involved in targeting and binding to the chloroplast
      membrane.

PMID- 8520627
TI  - Characterization of the intracellular GLUT-4 compartment.
AB  - Insulin stimulates glucose transport in muscle and adipose tissue by triggering
      the translocation of the glucose transporter GLUT-4 from intracellular vesicles
      to the cell surface. In the present study we have attempted to characterize the
      intracellular GLUT-4 compartment using vesicle immunoadsorption. Silver staining
      of this fraction indicates that this compartment contains numerous polypeptides
      that exhibit a marked change in mobility upon treatment with reducing agents. The
      polypeptide composition of GLUT-4-containing vesicles isolated from a variety of
      insulin-sensitive cell types, including heart, adipose tissue, skeletal muscle
      and 3T3-L1 adipocytes, is similar. In addition, the polypeptide composition of
      the GLUT-4 compartment isolated from CHO cells transfected with GLUT-4 resembles
      that observed in insulin-sensitive cells. Two major proteins in this vesicle
      fraction isolated from all cell types are the transferrin receptor (TfR) and the
      mannose 6-phosphate/IGF II receptor (MPR). Furthermore, vesicles immunoadsorbed
      from adipocytes, with antibodies specific for GLUT-4 and the TfR, also show
      conservation in their overall polypeptide composition. Protein micro sequencing
      of a major 80 kDa polypeptide enriched in the GLUT-4 compartment isolated from
      skeletal muscle revealed this protein to be rat transferrin. These data indicate
      that there is a close relationship between the intracellular GLUT-4 compartment
      and the endosomal system. Future studies will be required to determine if it is
      possible to isolate subcompartments within this system to determine if GLUT-4 is
      targeted to a specialized secretory compartment in insulin-sensitive cells or
      simply a subdomain within recycling endosomes.

PMID- 8520628
TI  - Influence of the spectrin network on fusion of influenza virus with red blood
      cells.
AB  - We examined the influence of the physical state of the membrane skeleton on low
      pH fusion of influenza virus A/PR 8/34 with intact human red blood cells.
      Spectrin, the major component of the skeleton, is known to become denaturated at
      50 degrees C. After heat treatment of erythrocytes at 50 degrees C we observed an
      enhanced kinetics of fusion monitored spectrofluorometrically by the
      octadecylrhodamine fluorescence dequenching assay, while the extent of fusion was
      not affected. The accelerated fusion of influenza virus after preincubation of
      red blood cells at 50 degrees C is not mediated by alterations of the lipid phase
      of the target. From ESR measurements using spin-labelled phospholipids we
      conclude that heat-induced alterations of the spectrin network did not affect
      either the phospholipid asymmetry or the fluidity of the exoplasmic and the
      cytoplasmic leaflets of the erythrocyte membrane. Moreover, as deduced from our
      previous investigations, the swelling behaviour of red blood cells could not be
      responsible for the observed effect. Possible mechanisms for the spectrin effect
      include a change in the ability of the target membrane to bend locally, and a
      change in the rate of formation and development of the fusion pore.

PMID- 8520629
TI  - The major integral membrane glycoprotein in adipocytes is a novel 200-kDa
      heterodimer.
AB  - The major glycoprotein in adipocytes was purified from rat adipocyte membranes by
      affinity chromatography with wheat germ agglutinin-agarose followed by DEAE
      Sepharose ion exchange chromatography. The protein had an apparent molecular
      weight of 200-kDa when analysed by SDS-PAGE under non-reducing conditions. When
      electroeluted from the gel, boiled in the presence of beta-mercaptoethanol, and
      re-analysed by gel electrophoresis, it was found to be composed of 100- and 160
      kDa subunits. The N-terminal sequences were determined through 20 amino acids for
      each subunit, were found to be identical, and were homologous with no previously
      described protein sequences. The protein was not extractable from the membrane by
      high salt concentrations, indicating it was an integral membrane protein.
      Membrane fractionation by differential ultracentrifugation showed it was present
      predominantly in the plasma membrane fraction. The protein was susceptible to
      cell surface radiolabelling, further suggesting it was a plasma membrane protein.
      In summary, the major membrane glycoprotein in adipocytes is a novel 200-kDa
      heterodimer whose disulfide-linked subunits possess identical N-terminal
      sequences.

PMID- 8520630
TI  - Evidence for glucuronide (small molecule) sorting by human hepatic endoplasmic
      reticulum.
AB  - The entry of substrates into, and the export of glururonides from, the lumen of
      hepatic endoplasmic reticulum (ER) in vitro (sealed microsomes) has been measured
      using radioactivity-labelled materials and a rapid filtration assay. Analysis of
      liver microsomes from a jaundiced patient showed the accumulation of bilirubin
      glucuronides within the lumen of the ER. Further analysis of these hepatic
      microsomes revealed that newly synthesized 1-naphthol glucuronide could exit from
      the microsomes whereas bilirubin glucuronide was accumulated within the
      microsomes. These results suggest the existence of mechanisms for the sorting of
      small molecules, destined for export through bile canalicular or basolateral
      plasma membranes, by ER. Furthermore, these sorting processes may be regulated by
      specific transporters within the ER.

PMID- 8520631
TI  - Techniques for the measurement of white adipose tissue metabolism: a practical
      guide.
AB  - A number of old and new techniques to study various aspects of white adipose
      tissue metabolism in vivo and in vitro are discussed. It is possible to determine
      lipolysis rates in vivo with tracer techniques using glycerol or fatty acids
      labelled with stable or radioactive isotopes. These methods allow the
      determination of whole body lipolysis rates but are not valuable for the
      investigations of regional variations in lipolysis. When combined they permit a
      calculation of the rate of re-esterification of free fatty acids. The vein
      draining abdominal subcutaneous adipose tissue can be cannulated in humans. By
      this method substrate turnover can be determined in vivo over the cannulated
      adipose region. With microdialysis it is possible to study local metabolism in
      vivo in different adipose tissue regions. At the same time it is possible to
      locally manipulate the tissue with metabolically active pharmacological
      substances. A number of in vitro methods to determine glucose transport in
      isolated fat cells are developed. The most accurate one uses 3-O-methyl glucose
      as tracer. These methods can be combined with studies of the further metabolism
      of glucose to lipids, lactate and carbon dioxide using simple (usually
      radioactive) methods. Lipolysis as well as release and re-esterification of free
      fatty acids can be investigated in detailed in vitro with sensitive techniques
      based on luminescence. Finally, triglyceride turnover and partial metabolism of
      acylglycerols can be investigated in vitro with a double isotope technique.

PMID- 8520633
TI  - Reliability of body fat distribution measurements. The ARIC Study baseline cohort
      results. Atherosclerosis Risk in Communities Study.
AB  - OBJECTIVE: To estimate the reliability of skinfold and girth measurements, and
      ratios involving these measurements, commonly used in epidemiological and
      clinical studies as measures of body fat distribution. DESIGN: Repeated
      measurements of body fat distribution measures were scheduled on randomly
      selected participants at the baseline clinical examination of the ARIC Cohort
      Study, by the same or by different technicians. SETTING: Probability sample of 45
      65 year old residents selected from four US communities. MEASUREMENTS:
      Subscapular and triceps skinfolds were taken twice using a Lange caliper on
      standardized right-side locations. Waist and hip girths were measured using an
      anthropometric tape applied at the level of umbilicus and of the maximal
      protrusion of the gluteal muscles, respectively. Repeated measurements were taken
      1-2 h apart. RESULTS: Inter-technician measurements of triceps skinfolds,
      subscapular skinfolds, waist girth, hip girth, and waist/hip ratio each had high
      reliability (R > 0.91). The reliability coefficient for triceps/subscapular ratio
      (R = 0.81) was somewhat lower. For skinfold measures, intra-observer coefficient
      of variations are lower than the ones observed in previous studies, and inter
      technician coefficient of variations are comparable. CONCLUSIONS: These results
      confirm previous findings which indicate that the reliability of girth
      measurements is greater than for skinfold measurements. As a consequence, the
      waist to hip ratio is less affected by measurement error than the skinfold ratio.
      Moreover, the expected gain in reliability from using the average of two skinfold
      measures, taken in succession, was not realized, indicating that when
      measurements are taken in rapid succession by the same technician, statistical
      independence between measures is questionable.

PMID- 8520632
TI  - Weight excess before pregnancy: complications and cost.
AB  - OBJECTIVE: To investigate the incidence of pregnancy complications and the cost
      of prenatal care in patients with pregravid overweight. DESIGN: Retrospective
      study of patients dispatched into four groups: normal weight, moderate
      overweight, obesity, massive obesity. SETTING: Department of Obstetrics and
      Gynecology of Montpellier. SUBJECTS: One hundred and twelve pregnancies among 89
      overweight women, compared with 54 healthy normal weight controls. MAIN OUTCOME
      MEASURES: Incidence of maternal complications, complications of labor, duration
      of hospitalization. RESULTS: Hypertension, toxemia, gestational diabetes, insulin
      treatment, urinary tract infections and macrosomia were positively correlated
      with maternal pregravid weight excess. Mean duration of hospitalization and
      overall cost were also strongly related to maternal weight. Cesarean section rate
      increased only in morbidly obese women. No materno-fetal mortality was observed
      in our study. CONCLUSION: Even moderate overweight is a significant risk factor
      for obstetrical complications and needs a multidisciplinary antenatal management
      in order to prevent materno-fetal complications.

PMID- 8520634
TI  - Improved glucose tolerance by acute vanadate but not by selenate exposure in
      genetically obese rats (fa/fa).
AB  - OBJECTIVE: To describe the impact of acute vanadate and selenate exposure on
      glucose tolerance of obese Zucker rats (fa/fa). DESIGN: Intravenous glucose
      tolerance tests (2.4 mmol/kg, continuously from 0 to 30 min) were performed in
      conscious Zucker rats exposed to a bolus-continuous infusion of sodium vanadate
      (2.45 mumol/h) or sodium selenate (0.90 and 2.45 mumol/h) and were compared to
      intraindividual control experiments with saline infusion. RESULTS: Vanadate
      infusion improved glucose tolerance and decreased insulin release, as shown by
      total areas under the curves (0-120 min: Glucose, min.mmol/l: control, 983 +/- 59
      vs vanadate, 915 +/- 54, P < 0.02; Insulin min.nmol/l: control, 117.5 +/- 19.9 vs
      vanadate, 88.5 +/- 26.2, P < 0.01). In contrast, infusion of selenate increased
      glucose induced insulin release during the first phase of the IVGTT (0-60 min,
      incremental area under the insulin curve: by 57% and 110% for low and high
      selenate infusion rate, respectively) and transiently improved glucose tolerance
      (0-60 min, decrease of incremental area under the glucose curve: 31% and 28%,
      respectively). That effect of selenate was lost with progression of the
      experiment during the second hour of the IVGTT, when plasma glucose continued to
      decline slowly in control experiments, but increased in selenate exposed rats
      without any adequate insulin secretory response to hyperglycemia. CONCLUSION: The
      results demonstrate improved glucose tolerance and decreased plasma insulin
      concentration during acute vanadate exposure. Only a transient insulinotropic
      effect with improved glucose tolerance is induced during acute selenate exposure,
      and is followed by progressive development of hyperglycemia indicating selenate
      toxicity.

PMID- 8520635
TI  - Reproducibility of computed tomography measurement of visceral adipose tissue
      area.
AB  - OBJECTIVE: The purpose of the current study is to examine the reproducibility of
      CT measurement of the cross-sectional area of abdominal adipose tissue. DESIGN:
      Sixteen healthy pre-menopausal women, ranging from lean to obese, underwent
      duplicate cross-sectional CT scans of the abdomen at the level of the 4th lumbar
      vertebral disc space. Subjects stood after the initial scan and were then re
      positioned prior to repeat CT scanning. RESULTS: There was a high degree of
      reproducibility in measurement of overall cross-sectional adipose tissue (AT) and
      in the partitioning of this into subcutaneous and visceral AT. The excellent
      reproducibility is demonstrated by a high correlation between duplicate
      measurements (r = 0.99, P < 0.01), and by small precision errors; 1.2% of the
      mean value for total AT cross-sectional area, 1.9% for subcutaneous AT area, and
      3.9% for visceral AT area. CONCLUSION: Measurement of abdominal AT area by cross
      sectional CT scanning is not only an accurate determination of this adipose depot
      but can also be repeated with a high degree of precision.

PMID- 8520636
TI  - Frequency of eating occasions and weight change in the NHANES I Epidemiologic
      Follow-up Study.
AB  - OBJECTIVE: To examine the association of frequency of eating occasions with
      prospective, and retrospective weight change. DESIGN: Data from the NHANES I
      (1971-75) Epidemiologic Follow-up Study (NHEFS, 1982-84) (n = 7147) was used.
      Weight change was defined as the difference between the weight measured at follow
      up in 1982-84 and the weight measured at baseline in 1971-75. Baseline frequency
      of eating occasions was estimated by summation of actual times at which food was
      reported consumed in a 24-h dietary recall. Follow-up frequency of eating was
      estimated from subject responses at follow-up to number of meals and snacks
      consumed daily. RESULTS: Men and women reported (mean +/- s.e.) baseline
      frequency of 5.3 +/- 0.06 and 4.9 +/- 0.03 eating occasions, respectively.
      Frequency of eating occasions at follow-up was 3.6 +/- 0.02 occasions in both men
      and women. Baseline body mass index and frequency of eating were inversely
      related in multivariate regression analyses in both men and women (P < 0.02).
      Regression analyses adjusted for multiple covariates showed no association
      between weight change and frequency of eating at baseline or follow-up.
      CONCLUSION: Baseline frequency and subsequent weight change or follow-up
      frequency and preceding weight change were unrelated in the NHEFS cohort.

PMID- 8520637
TI  - Cardiovascular and catecholamine response to clonidine in obese subjects.
AB  - OBJECTIVE: To investigate central alpha-2 adrenergic activity, one of the main
      inhibitory factors affecting norepinephrine secretion, in human obesity. DESIGN:
      Cardiovascular and catecholamine responses to clonidine (300 micrograms per os)
      were evaluated in a group of obese subjects. SUBJECTS: 10 obese men (OM) and 14
      obese women (OW). MEASUREMENTS: Mean arterial pressure, pulse rate, plasma
      norepinephrine (NE) and epinephrine (E) before and 120', 130', 140' after
      clonidine (CL) administration. RESULTS: The mean arterial pressure decreased
      after CL administration in obese patients (from 92 +/- 12 to 79 +/- 2 mmHg; P <
      0.001) with no significant differences between OM and OW. The values of pulse
      rate were reduced in obese patients after clonidine (60 +/- 1 b/min vs 65 +/- 1
      b/min before clonidine; P < 0.01) with no differences between OM and OW. Plasma E
      was not affected by the administration of clonidine and no sex related
      differences were found in the basal (OM: 0.23 +/- 0.03 vs OW: 0.15 +/- 0.03
      nmol/L; P = NS) and in the post-CL E levels (OM: 0.22 +/- 0.02 vs OW: 0.14 +/-
      0.03 nmol/L; P = NS). Basal plasma NE values were not different between OM (1.32
      +/- 0.15 nmol/L) and OW (1.03 +/- 0.11 nmol/L; P = NS). Plasma NE decreased after
      CL in obese patients (from 1.20 +/- 0.10 to 0.59 +/- 0.08 nmol/L; P < 0.001) and
      a significant difference was found in the post-CL values between OM and OW (0.74
      +/- 0.11 vs 0.40 +/- 0.06 nmol/L respectively; P < 0.01). The decrease in plasma
      NE was strongly correlated with the basal value of NE (r = 0.70; P < 0.001). The
      sex-related differences in plasma NE responses to clonidine in obese subjects did
      not differ with those previously observed in control subjects (P = NS).
      CONCLUSION: The cardiovascular and catecholamine response to CL in obese patients
      were similar to that previously observed in normal subjects, indicating a normal
      alpha-2 adrenergic activity. The sex related difference in the NE response to CL,
      previously reported in normal subjects, was maintained in obese patients.

PMID- 8520638
TI  - The effect of discontinuing dehydroepiandrosterone supplementation on Zucker rat
      food intake and hypothalamic neurotransmitters.
AB  - OBJECTIVE: Dehydroepiandrosterone (DHEA) decreases body weight and food intake of
      the obese Zucker rat, a model of youth-onset obesity associated with hyperphagia.
      The effects of discontinuing DHEA treatment on these parameters, however, has not
      been investigated. This question was studied in rats that had been maintained on
      DHEA-supplemented (0.0%, 0.06%, 0.15%, 0.3% or 0.6%) diets for 7 days. METHOD:
      The results were correlated with regional levels of hypothalamic
      neurotransmitters in rats treated with 0.6% DHEA for 7 days in a separate
      experiment. Neurotransmitter changes were evaluated after Day 0 (7 days of
      treatment), and Day +1 and Day+2 post-DHEA. RESULTS: Upon removing dietary DHEA,
      rats immediately (+1 day) consumed significantly more food than while on the DHEA
      supplemented diet. Indeed, they consumed even more food than the group that had
      always been on the DHEA-free diet. This intake above control lasted for as long
      as +9 days post-DHEA treatment. After 7 days of DHEA treatment, lateral
      hypothalamic (LH) serotonin (5-HT) and dopamine (Dpm) were elevated significantly
      (P < 0.05) immediate changes in 5-HT and Dpm returned to baseline by day 2 of
      post-DHEA treatment. No significant changes occurred in either the ventromedial
      hypothalamus (VMH) or the paraventricular nucleus (PVN). CONCLUSIONS: These
      observations suggest that there is a possible relationship between increases of
      LH 5-HT and Dpm with 0.6% DHEA treatment. Both are inhibitory to food intake and
      DHEA at the 0.6% dose causes hypophagia after 7 days of treatment (i.e. 0 days).
      Subsequent decreases of these monoamines occurred during the post-DHEA period at
      both +1 and +2 days. Return of these inhibitory monoamines to baseline could be
      responsible for reversal of the hypophagia, however, they do not rule out the
      production of a separate stimulator of food intake.

PMID- 8520639
TI  - Gastric distension, hunger and energy intake after balloon implantation in severe
      obesity.
AB  - OBJECTIVE: To investigate the interrelationships between satiety feelings,
      abdominal perception, energy intake and weight loss, related to the presence of
      an intragastric balloon. DESIGN: Randomized double blind study. SUBJECTS: 20
      severely obese subjects, BMI > 40 kg/m2, randomly assigned either to receive an
      air filled balloon (n = 11) or to have a sham procedure (n = 9). All subjects had
      dietary counselling to help them follow a relatively low energy diet (60% of
      individual spontaneous intake). MEASUREMENTS: During biweekly visits, body weight
      was recorded, visual analogic scales for stomach distension, hunger and feeling
      of balloon presence were completed. Blood chemistry profiles were monitored once
      every 4 weeks. RESULTS: In the balloon group, the sensations related to the
      presence of the balloon and to abdominal distension dramatically increased after
      insertion, and plateaued during the next 4 weeks. Both feelings of presence and
      distension decreased thereafter, and after 10 weeks they were not significantly
      different from those of the sham balloon group. Hunger dramatically decreased to
      about 30% of initial rating in the first week, but slowly returned to the initial
      value by the 12th week. Hunger feelings were highly and negatively correlated
      with feelings of distension. During the same period, the sham balloon group
      continued to maintain the low energy intake, and did not register any feelings of
      distension or presence; hunger level did not differ from initial levels
      throughout the whole study. The energy intake and the rate of weight loss (8-9
      kg) was similar in the two groups during the study, and were not correlated with
      the feelings of distension. CONCLUSION: This study showed that in severely obese
      subjects submitted to a restrictive diet, an intragastric balloon has a
      measurable but transient effect on the sensation of epigastric distension and is
      able to decrease feelings of hunger. Unfortunately, these effects were not
      associated with a lower energy intake or a higher rate of weight loss than the
      sham situation. Thus, the present study does not support the interest of such a
      balloon (500 ml, air filled) in the treatment of severe obesity.

PMID- 8520640
TI  - The response to treatment of overweight in postmenopausal women is not related to
      fat distribution.
AB  - OBJECTIVE: To investigate whether fat distribution or sex hormone status in
      overweight postmenopausal women do influence the response to treatment of
      overweight. DESIGN: Longitudinal, clinical intervention study of a 4.2 MJ diet
      daily with or without exercise. SUBJECTS: 98 healthy, overweight, postmenopausal
      women (age: 49-58 y, BMI: 25-42 kg/m2). MEASUREMENTS: Various fatness and fat
      distribution parameters (by dual-energy x-ray absorptiometry and anthropometry),
      sex hormone-binding globulin (SHBG), sex hormones, and the resting energy
      expenditure (REE) at baseline and after 3 months. RESULTS: Reductions in weight
      and fat were independent of the initial fat distribution and the REE, but were
      significantly associated with high initial SHBG levels. Furthermore, loss of fat
      was significantly and independently associated with increases in SHBG and
      reductions in central fat distribution. CONCLUSION: Postmenopausal women with an
      android and gynoid fat distribution respond with similar weight loss to treatment
      of overweight. Furthermore, a more healthy, less android, fat distribution and
      sex hormone status may be achieved with increasing weight loss.

PMID- 8520641
TI  - Dexfenfluramine inhibits catecholamine stimulated in vitro lipolysis in human fat
      cells.
AB  - OBJECTIVE: To investigate the effect of dexfenfluramine (d-F) on basal and
      isoproterenol stimulated lipolysis in human fat cells in vitro. DESIGN:
      Adipocytes were incubated in Krebs-Ringer-Hepes buffer either with 10(-6) M or
      10(-7) M isoproterenol alone, with 0.02-200 micrograms/ml (74.7 nmol/l-747
      mumol/l) of d-F or both. MEASUREMENTS: Glycerol release at 2 h incubation time
      was measured as an estimate for lipolysis. RESULTS: The addition of d-F did not
      significantly influence basal lipolysis of 58.6 nmol/2 h. Stimulation by 10(-6) M
      and 10(-7) M isoproterenol increased glycerol release to 92.5 nmol/2 h and 83.4
      nmol/2 h, respectively. Adding increasing doses of d-F and 10(-6) M isoproterenol
      caused a dose-dependent inhibition of isoproterenol stimulated lipolysis.
      Glycerol release was significantly decreased to 84.1 nmol/2 h at 20
      micrograms/ml, to 77.8 nmol/2 h at 60 micrograms/ml and to 61.9 nmol/2 h at 200
      micrograms/dl d-F. Glycerol release induced by 10(-7) M isoproterenol was
      significantly inhibited to 69.7 nmol/2 h at 20 micrograms/ml, to 61.5 nmol/2 h at
      60 micrograms/ml and to 51.9 nmol/2 h at 200 micrograms/ml d-F. 50% inhibition
      occurred at 80 micrograms/ml d-F with 10(-6) M isoproterenol and at 28
      micrograms/ml with 10(-7) M isoproterenol. CONCLUSION: d-F may decrease the
      release of free fatty acids from adipose tissue. This would lead to a reduced
      flux to the liver and may partly account for the triglyceride lowering effect of
      d-F in obese subjects.

PMID- 8520642
TI  - Advanced RUS and normal carpal bone age in childhood obesity.
AB  - METHODS: Skeletal maturation was evaluated in 60 prepubertal children aged 7.7 +/
      0.27 years (range 2.7-12.6). The radius, ulna and short bones (RUS) and the
      carpal (CARP) bone age were assessed. Height corresponded to 1 +/- 0.1 Z scores.
      RESULTS: RUS bone age was 1.04 +/- 0.2 years more advanced than chronological age
      (P = 0.0001). CARP bone age was only 0.2 +/- 0.2 years more advanced than
      chronological age and the difference was not significant. However, the degree of
      advancement of CARP bone age in respect of chronological age was significantly (P
      = 0.0001) correlated with height Z scores. CONCLUSIONS: CARP bone age is less
      sensitive than RUS bone age to the factors promoting the early skeletal
      maturation in obese children. Nevertheless, the degree of CARP bone age
      advancement, although minimal, is correlated with overheight.

PMID- 8520643
TI  - [Nitric oxide: new horizons in gynecology and obstetrics].

PMID- 8520644
TI  - [Electrosurgery. Principles and practical uses].

PMID- 8520645
TI  - [Karyotyping in couples with subfertility and infertility].

PMID- 8520646
TI  - [Age and fertility: value of endometrial co-cultures].
AB  - Embryo coculture system may contribute to understand the mechanisms underlying
      the decrease of fertility with aging. We report here our experience of coculture
      on maternal endometrial cells and histology of endometrial biopsy in 90 patients
      with repeated failures of implantation. Histology dating failed to find any age
      related changes. In coculture system, it is obvious that embryo viability
      diminishes with aging, but for equal embryonic quality, the maternal age does not
      interfere significantly on pregnancy rate. Anyway the number of first trimester
      abortions seems higher in older women. Coculture system emphasizes the major role
      of oocyte aging in the decrease of fertility and may be useful to establish a
      prognostic in IVF for older patients.

PMID- 8520647
TI  - [Hydrosalpinx and sterility: indications for salpingectomy].

PMID- 8520649
TI  - [Pregnancy after diagnosis of menopause].
AB  - Menopause is a probability diagnosis. Menopause does not mean permanent
      infertility, particularly in the case of premature menopause. We have realised a
      national enquiry in order to precise the pregnancy phenomenon after diagnosis of
      menopause. We found 116 pregnancy cases, which occurred 2.4 years (average) after
      menopause diagnosis. Pregnancies occur more often in the case of premature
      menopause and seem to be favoured by hormonal replacement therapy.

PMID- 8520648
TI  - [Ectopic molar pregnancy. Two cases in sixteen years].
AB  - Two cases of hydatidiform pregnancy tubal located occurred in 16 years are
      reported by the authors. The uncommon frequency of this pathology is difficult to
      state precisely due to the limited possibilities of diagnosis. Theses are
      inherent to the lack of statement of ectopic pregnancy, a non systematic
      histologic test, the genital infections main causes of ectopic pregnancy in areas
      where its rage of endemic. The inaugural clinic scene was the same as ectopic
      pregnancy one in a state of rupture. The emergency therapy is surgical,
      essentially the tubal resection, completed by a chemotherapy. The prognosis and
      the leading therapy have to be specify.

PMID- 8520650
TI  - [Management of necrospermia].
AB  - Necrospermia is still a poorly documented cause of male infertility. Among
      infertile subjects, the incidence reported in the literature is 0.2 to 0.48 per
      cent. We undertook a retrospective study to contribute to the comprehension of
      this abnormality. Histories, physical examination, analysis of the semen and
      hormonal dosages performed in necrozoospermic subjects were reviewed. We observed
      that in patients with necrospermia in at least three semen samples, infections
      represent 40 per cent of aetiologies. In 20% of the whole population, no
      aetiology was observed, but abnormalities of the epididymis function was
      suggested. Through this study, we suggest an aetiological classification and
      practical guidance in case of necrozoospermia.

PMID- 8520652
TI  - [Total hysterectomy for benign pathologies: why is laparoscopy of value?].
AB  - The majority of the hysterectomies are performed by laparotomy. With laparoscopic
      surgery it will be possible to perform only 10 to 20 per cent of the
      hysterectomies by the abdominal route. Even if laparoscopic hysterectomy is a
      feasible technique, all the hysterectomies should not be performed by the
      endoscopic route. Laparoscopic surgery is in no case an alternative to vaginal
      surgery. Laparoscopic surgery is not indicated for hysterectomy if the operation
      is feasible quickly and under good conditions via the vaginal route. Laparoscopic
      surgery is only indicated when vaginal surgery is difficult and/or contra
      indicated. In these situations, laparoscopic surgery can be performed according
      two different modalities: laparoscopically assisted vaginal hysterectomy and
      total hysterectomy completely performed by laparoscopy.

PMID- 8520651
TI  - [Detection of Chlamydia trachomatis infection by PCR in first voided urines in
      men].
AB  - The goal of this study was to evaluate whether the new commercially available PCR
      based assay Amplicor C. trachomatis (Roche Molecular Systems) could improve the
      diagnosis of chlamydial urogenital infections in men, compared with cell culture
      of C. trachomatis considered as the reference method. A total of 466 men
      attending the STD clinic were tested by the Amplicor test in urine and by cell
      culture in urethra. The prevalence of C. trachomatis was 13.7% (64/466) by cell
      culture and 14.4% (67/466) by the Amplicor test. After resolution of the
      discrepant results, the sensitivity of culture was 91.4% in male urethral
      specimens. The resolved sensitivity of the PCR assay was 92.7% in male urine and
      the specificity was 99.5%. We concluded that this rapid PCR-based assay showed an
      improvement in quality for diagnosing C. trachomatis infections in men.

PMID- 8520653
TI  - [Thyroid ultrasonography and infertility].
AB  - In about 60% of infertile women, clinical or subclinical thyroid disorders can be
      diagnosed, and specific treatment provides significant improvements of fertility.
      Sonographic thyroid examination is easily performed and can detect thyroid
      abnormalities. So it's well-founded to say that it should be included in female
      infertility investigations.

PMID- 8520654
TI  - [Does fetal sexuality exist?].
AB  - From a personal observation of a male fetus oro-genital contact we made a
      preliminary multicentric study which shows some rare similar cases. Others oral
      or manual behaviours, containing perhaps some sexual significance are frequently
      observed but not yet published.

PMID- 8520655
TI  - Cyclosporine in the treatment of rheumatoid arthritis.

PMID- 8520656
TI  - Vasculitis.

PMID- 8520657
TI  - Iatrogenic hallux varus surgical procedure: a study of 14 cases.
AB  - Hallux varus occurs most frequently as a result of excessive surgical correction
      of musculoligamentous imbalance around the metatarsophalangeal (MTP) joint of the
      great toe (lateral release and medial capsuloligamentous tensioning). If
      untreated, the condition may lead to motion loss and degenerative arthritis. In
      this series, 14 cases of hallux varus were treated. Medial arthrolysis was done
      in each case. In five cases, reconstruction of the lateral ligament (with a 1.5
      mm Ligapro suture), using a new technique, accompanied the medial release.
      Arthrodesis of the MTP was done in nine cases treated when there was already
      stiffness and arthrosis. According to a 100-point scoring system, the results
      were excellent in 56% and good in 44% of the MTP joint arthrodesis cases. Results
      were excellent in 100% of the mobilizing technique cases using Ligapro suture.

PMID- 8520658
TI  - Influence of extrinsic plantar flexors on forefoot loading during heel rise.
AB  - This investigation studied the effects of simulated plantar flexor muscle
      activity on forefoot loading using a static cadaver model. Nine cadaver feet were
      mounted in an apparatus in the heel rise position. Using computer-controlled and
      pneumatic actuators, forces were simultaneously applied to the tendons of the
      triceps surae, flexor hallucis longus, flexor digitorum longus, peroneus brevis
      and longus, and tibialis posterior until 750 N of ground reaction force was
      achieved, at which time forefoot plantar pressure patterns were captured
      immediately with a pedobarograph. Second metatarsal bending moments were
      calculated from strain gauge data collected concurrently. Consecutive loading
      cycles were performed with sequential elimination of simulated muscle force from
      each tendon except the Achilles. Loss of simulated flexor hallucis longus
      activity significantly decreased great toe contact forces and significantly
      increased forces under the forefoot. Simulated loss of both the flexor hallucis
      longus and flexor digitorum longus caused significant decreases in contact area,
      pressure, and force beneath the toes and significant increases in contact area
      and force under the forefoot. Bending moments in the second metatarsal were shown
      to vary directly with peak pressure under the second metatarsal head (r = 0.801).
      These findings demonstrate the load distributing function of the extrinsic
      plantar flexors during heel rise.

PMID- 8520659
TI  - Cylindrical cemented ankle arthroplasty: a prospective series with long-term
      follow-up.
AB  - From 1981 to 1985 28 ankle arthroplasties were performed using a congruent and
      cylindrical ankle design. The talus component was an anatomically shaped cap to
      cover the talus dome and the facets. The tibial component was congruent toward
      the talus and had two parallel bars on the back for fixation into the distal
      tibia. The diagnosis was osteoarthritis in 15 cases and rheumatoid arthritis in
      11 cases (two bilateral cases). There were seven failures, giving a cumulative
      estimated survival rate of 70% for the prosthesis at 12 years.

PMID- 8520660
TI  - Anatomy of the plantar plate and its attachments in the lesser metatarsal
      phalangeal joint.
AB  - The plantar plate is a rarely seen, yet central structure to the lesser
      metatarsal phalangeal (MP) joint. Thirty cadaver lesser MP joints were studied to
      obtain a detailed description of the plate, including its dimensions,
      connections, and histology. The plate was found to be made of fibrocartilage with
      fiber orientation which suggests that it withstands tensile loads in line with
      the plantar fascia as well as the compressive loads from the metatarsal head. The
      plantar plate was the most substantial distal insertion of the plantar fascia.
      Impressive plantar plate attachments were noted to the proximal phalanx, the
      major longitudinal bands of the plantar fascia, and the collateral ligaments. The
      plate and collateral ligaments formed a substantial soft tissue box connected to
      the sides of the metatarsal head. From the dissections, it is apparent that
      malposition of the toe at the MP joint is likely over time to be associated with
      pathology in both the collateral ligaments and the plate. Because of these
      attachments and a close association with the flexor tendons to the lesser toe,
      the plate can be compared with the sesamoid mechanism of the first MP joint.

PMID- 8520661
TI  - Silastic single-stem implants in the treatment of hallux rigidus.
AB  - Forty cases of hallux rigidus treated by Silastic hemiarthroplasty over an
      average period of 110 months have been reviewed here. As many as 36% (14 feet) of
      the patients were unhappy with the results of their operation. Six implants had
      to be removed because of increasing pain and fragmentation of the prosthesis.
      These patients improved after the prosthesis was removed. It is concluded that
      Silastic hemiarthroplasty does not give an acceptable level of good results when
      compared with published reports of other forms of treatment. The probable causes
      of the high dissatisfaction rate are discussed.

PMID- 8520662
TI  - Kinematics of the normal arch of the foot and ankle under physiologic loading.
AB  - We studied 15 cadaver feet to determine three-dimensional motion of selected
      tarsal bones under axial loading at three different loading levels. We determined
      the motion of individual joints and also the rotation of the tarsal bones in
      relation to the tibia. Joint rotations increased consistently with higher loads.
      The naviculartalar joint had the greatest total screw axis rotation, which
      averaged 9.4 degrees +/- 2.2 degrees at 667 N of load, followed by the first
      metatarsal-navicular (mean, 7.2 degrees +/- 1.5 degrees), talartibial (mean, 5.2
      degrees +/- 1.6 degrees), and calcaneal-talar (mean, 4.4 degrees +/- 1.7 degrees)
      joints. The observed changes indicate the need for assessment of foot and ankle
      alignment clinically and radiologically while the patient is weightbearing.

PMID- 8520663
TI  - Kidner procedure for symptomatic accessory navicular and its relation to pes
      planus.
AB  - The role of relocation of tibialis posterior tendon insertion in the treatment of
      symptomatic accessory navicular and its relation to the pes planus was studied in
      28 patients with symptomatic accessory navicular. Two hundred non-affected
      individuals were used as control. The calcaneal pitch angle measured
      radiographically, was used as an indicator of pes planus. All patients had had an
      excision of the accessory navicular and relocation of the tibialis posterior
      tendon insertion (Kidner procedure). The average follow-up was 3.2 years. The
      results were good in 27 patients, and fair in 1 patient, and there were no poor
      results. Most of the patients demonstrated that the pain and the fatigue signs of
      the foot and the leg have been improved. Only 3 of 25 patients clinically showed
      an improvement of the medial longitudinal arch. The calcaneal pitch angle in
      patients with symptomatic accessory navicular was significantly (14.8 degrees)
      lower than that in normal subjects (21.4 degrees). An association of pes planus
      and symptomatic accessory navicular was shown. The Kidner procedure gave good
      results in the relief of pain and fatigue in patients with symptomatic accessory
      navicular. The procedure did not significantly restore the height of the medial
      arch.

PMID- 8520664
TI  - Kirschner wire breakage after surgery of the lesser toes.
AB  - A retrospective review was made of all patients operated on by the two senior
      authors from January 1985 to January 1993 for problems with Kirschner wire
      breakage following forefoot surgery. Thirty-three broken K-wires in 27 patients
      were encountered. All of these were 0.045-inch K-wires that had been placed
      across the metatarsophalangeal (MTP) joint of the lesser toes. In no case was
      there breakage of a K-wire that was larger than 0.045 inches or that did not
      cross the MTP joint. The medical records and radiographs of 565 consecutive
      patients having fixation with 0.045-inch K-wires that crossed the MTP joints of
      the lesser toes were then reviewed. A total of 1002 K-wires were used with an
      overall failure rate of 3.2% (4.8% of the patients). All of these K-wires failed
      just proximal to the point of entry into the metatarsal head. No intra-articular
      retained fragments were noted. Twenty-five of the retained fragments were
      completely within the metatarsal head and shaft, and eight of these fragments
      pierced the cortex of the metatarsal proximally. Twenty-three patients with
      retained fragments were examined in follow-up and in no case could the retained
      fragment be palpated or directly related to postoperative symptoms. Of the three
      patients who complained of persistent pain, two had mild pain with persistent MTP
      synovitis and one had severe pain due to lateral deviation of the toe after
      surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520665
TI  - Ground reaction torque and pathway of point of application of ground reaction
      force during gait of intoeing children.
AB  - One hundred twenty-four children with intoeing and 80 age-matched controls were
      investigated with the Kistler force plate. Tr2, reflecting the maximum external
      rotational ground reaction torque, is reduced by 30% to 40% in all intoeing
      children. There also is an appreciably shorter pathway of the point of
      application of the ground reaction force in the Y-direction (from 20% to 25%) and
      an obvious medial shift of the point of application of the ground reaction force
      in the X-direction (from 105% to 290%), from heel strike to toe-off as compared
      with controls. In spontaneous correction of intoeing, point of application of the
      ground reaction force in the X-direction becomes more close to normal. The "foot
      progression angle," which can easily be calculated from the force plate
      measurements to judge the degree of intoeing, is different from the values in the
      literature.

PMID- 8520666
TI  - In vitro kinematics of the axially loaded ankle complex in response to
      dorsiflexion and plantarflexion.
AB  - The rotational movements of the tibia and calcaneus that occur with dorsiflexion
      plantarflexion and axial loading were studied in cadaver foot-leg specimens using
      an unconstrained testing apparatus. Independent of the foot flexion position,
      significant internal rotation of the tibia and eversion of the calcaneus were
      noted after the ankle complex was axially loaded. Independent of loading, 10
      degrees of dorsiflexion resulted in 0.1 degrees of eversion and 2.1 degrees of
      internal rotation of the tibia. Conversely, 10 degrees of plantarflexion resulted
      in 1.6 degrees of inversion and 1.3 degrees of external rotation of the tibia.
      The induced rotational movements of the tibia and the calcaneus differed
      significantly between the specimens. These results suggest that the foot "axes"
      did not change by axially loading the ankle complex and they support previous
      reports that the ankle complex uses different axes for dorsiflexion and
      plantarflexion.

PMID- 8520667
TI  - Late flexor digitorum longus tendon rupture after transfer for posterior tibial
      tendon insufficiency: a case report.
AB  - A 64-year-old woman was treated for an idiopathic complete rupture of the
      posterior tibial tendon with transfer of the flexor digitorum longus tendon to
      the navicular. After an initial excellent result, she returned 41 months later
      after experiencing a sudden pop in the medial retromalleolar area, followed by
      progressive medial ankle pain. At reoperation, a complete rupture of the flexor
      digitorum longus tendon was noted at its insertion into the navicular.
      Reconstruction was performed utilizing a sliding lengthening of the flexor
      digitorum longus tendon and reattachment to the navicular with a suture anchor.
      Clinical improvement was noted at the 12-month follow-up evaluation. This case
      presentation is of clinical interest, as late acute failure of a flexor digitorum
      longus tendon transfer for posterior tibial tendon rupture has not been reported
      previously.

PMID- 8520668
TI  - Microcalorimetric characterization of the anion-exchange adsorption of
      recombinant cytochrome b5 and its surface-charge mutants.
AB  - The adsorption of recombinant soluble tryptic fragment of rat cytochrome b5 on
      the strong anion exchanger Mono Q was studied using isothermal titration
      calorimetry and differential scanning calorimetry (DSC). Titration calorimetry
      results obtained at low levels of adsorbed protein show increasingly endothermic
      (unfavorable) enthalpies of binding with increasing surface coverage, confirming
      the heterogeneous nature of binding. The enthalpy of adsorption declines toward
      zero at higher loadings. At low surface coverage, enthalpies increase linearly
      with temperature, giving rise to a positive value of delta Cp. Enthalpies of
      adsorption depend strongly on the history of the adsorbent. DSC is used to show
      that cytochrome b5 is stable in both free and adsorbed states at all temperatures
      used in the titration calorimetric experiments. Site-directed mutants of
      recombinant cytochrome b5 carrying single charge-neutralizing substitutions are
      used to test the contributions of particular residues to the thermodynamics of
      adsorption. Like those derived from van't Hoff analysis of equilibrium adsorption
      isotherms and HPLC retention data, calorimetric enthalpies of adsorption are
      positive, confirming the dominant role of entropic effects in ion-exchange
      adsorption in this system.

PMID- 8520669
TI  - Quantitation of monoclonal antibodies by perfusion chromatography
      immunodetection.
AB  - The ImmunoDetection PG (protein G) cartridge which is based on perfusion
      chromatography has been evaluated for the quantitation of murine monoclonal
      antibody (IgG1) in biological fluids. The results indicate a low intra-day
      coefficient of variation (C.V.) < or = 5% and a sample analysis time of 5.5 min.
      A standard curve generated using injection of known amounts of monomeric antibody
      against the eluted peak area shows linearity (r2 = 0.99) over the 0.1-100
      micrograms range. The minimum detectable concentration (MDC) at 280 nm is about 2
      micrograms/ml which can be decreased to 200 ng/ml if the antibody elution is
      monitored at 214 nm. Under these conditions the C.V. is < or = 5%. Accuracy of
      the quantitation is independent of operator, solution composition, sample pH and
      the ionic strength, all of which are factors to consider in performing
      immunoassays. Antibody samples containing aggregated and fragmented Fc regions of
      the antibody will interfere with this method of quantitation. An optimized
      validated method for the quantitation of antibody is described. This mode of
      perfusion chromatography could be applied in the biopharmaceutical field due to
      its speed, efficiency and sensitivity.

PMID- 8520670
TI  - Unusual chromatographic behaviour and one-step purification of a novel membrane
      proteinase from Bacillus cereus.
AB  - Cell envelopes of Bacillus cereus contain a casein-cleaving membrane proteinase
      (CCMP) and an insulin-cleaving membrane proteinase (ICMP), which differ in their
      substrate and inhibitor specificity from all Bacillus proteinases described
      previously. They remained localized in the cytoplasmic membrane after treatment
      with lysozyme and mutanolysin and they are strongly attached to the membrane
      compared with other known membrane proteinases. Only high a concentration of the
      Zwitterionic detergent sulfobetain SB-12 enabled an effective solubilization of
      both membrane proteinases. The usual conventional purification methods, such as
      chromatofocusing, ion-exchange chromatography and hydrophobic interaction
      chromatography in the presence of detergent concentrations beyond their critical
      micelle concentration, could not be applied to the purification, because the
      solubilized membrane proteinases bound strongly and irreversibly to the
      chromatographic matrix. In the search for other purification methods, we used a
      tentacle ion-exchanger (EMD trimethylaminoethyl-Fractogel) to reduce the
      hydrophobic interactions between the proteinases and the matrix. All
      contaminating proteins could be removed by a first gradient of sodium chloride
      without elution of CCMP; a second gradient with isopropanol and a decreasing salt
      concentration resulted in an efficiently purified CCMP. The ICMP was irreversibly
      denaturated. Purified CCMP is a member of the metalloproteinase family with a pH
      optimum in the neutral range and a temperature optimum of 40 degrees C, whose
      properties differ from the serine-type membrane proteinase of Bacillus subtilis
      described by Shimizu et al. [Agric. Biol. Chem., 47 (1983) 1775]. It consists of
      two subunits in sodiumdodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) under reducing conditions (Mr 53,000 and 65,000); however, the molecular
      mass of the purified enzyme could not be determined by size exclusion or SDS
      PAGE, because the purified enzyme aggregated at the top of the gel matrix. CCMP
      solubilized before the purification process, could be eluted in the presence of
      0.1% octylphenol-poly(ethyleneglycol ether)9-10 (Triton X-100) in two peaks of Mr
      56,000 and 128,000, respectively. We discuss this special chromatographic
      behaviour of the CCMP from Bacillus cereus, with regard to the strong hydrophobic
      interactions of the enzyme with the chromatographic matrix and additional self
      aggregation, which could only be dissolved by solvents such as isopropanol.

PMID- 8520671
TI  - Enantiomeric resolution using the macrocyclic antibiotics rifamycin B and
      rifamycin SV as chiral selectors for capillary electrophoresis.
AB  - Rifamycin B and rifamycin SV belong to the class of macrocyclic antibiotics known
      as ansamycins. These macrocyclic antibiotics were used as chiral selectors in
      capillary electrophoresis to enantioselectively resolve a number of chiral
      compounds. They contain groups capable of providing the types of multiple
      interactions necessary to achieve chiral recognition between enantiomers. In
      fact, they appear to be complimentary in the types of compounds they can
      enantiomerically resolve. Rifamycin B is shown to be enantioselective towards
      positively charged compounds, while rifamycin SV was enantioselective towards
      negatively charged solutes. The choice of wavelength for detection significantly
      affects sensitivity. Monitoring one of the wavelengths which coincide with the
      absorption minima of the chiral selector enhances sensitivity. Resolution is
      enhanced by keeping the amount of analyte injected on column as low as possible
      and it is demonstrated that it is possible to detect as little as 0.1% of one
      enantiomer in the presence of the other enantiomer using indirect detection.

PMID- 8520672
TI  - Optimization of the separation of beta-agonists by capillary electrophoresis on
      untreated and C18 bonded silica capillaries.
AB  - The conditions of the separation of ten beta-agonists by capillary zone
      electrophoresis were studied. Several buffers were tested at different ionic
      strengths and different pH  values. The experiments were carried out on two
      different supports, i.e. an untreated fused-silica capillary and a C18 covalently
      bonded silica capillary. The results showed that the optimum pH value was the
      same for the two capillaries. Separation efficiencies were slightly better for
      the fused-silica capillary whereas better selectivity and repeatability were
      obtained with the C18 bonded capillary, under optimal conditions.

PMID- 8520673
TI  - Determination of styrene oxide adducts in DNA and DNA components.
AB  - The reaction of styrene oxide with DNA components was studied using separation by
      capillary zone electrophoresis (CZE) and detection by negative-ion electrospray
      mass spectrometry (MS). The CZE-MS interface was built for a sector field mass
      spectrometer. The reaction of styrene oxide with mononucleotides (dGMP, dAMP) was
      used to optimize the relevant separation parameters and to gather the first
      information about the behaviour of the possible products. With these mixtures,
      sample stacking procedures were developed and the scope of collision-induced
      dissociations were studied. From the fragments recorded, information about the
      reaction sites in the nucleotides was obtained. Further, the reaction with intact
      calf thymus DNA was investigated. The DNA was digested into oligonucleotides
      using the previously described approach with Benzonase, an unspecific nuclease,
      and alkaline phosphatase. Styrene oxide mono-adducts in dinucleotides,
      trinucleotides and tetranucleotides were detected, whereas pentanucleotides
      exhibit mono- and discernible amounts of di-adducts. The hexanucleotides were
      generally modified twice. The alkylated species moved faster than the unmodified
      oligomers.

PMID- 8520674
TI  - Capillary electrophoresis of DNA potential utility for clinical diagnoses.
AB  - The last few years have witnessed a tremendous shift in the use of capillary
      electrophoresis for clinical applications, particularly with DNA analysis. As a
      result of the large number of DNA-based clinical assays, there is an intense
      interest in making DNA analysis faster, less expensive and more automated. We
      describe the evaluation of CE-based single-strand conformation polymorphism
      (SSCP) and dideoxy fingerprinting (ddF) analysis for the detection of single
      point mutations within a Mycobacterium tuberculosis-specific amplified DNA
      fragment. Both were found to be capable of detecting the mutation in the
      resistant isolate but ddF showed the most promise with respect to specificity and
      ease of implementation. In addition, initial results with a CE-based sizing
      method is shown to be competitive and, perhaps, superior to a Southern blot
      analysis for the detection of hepatitis C viral (HCV) infection.

PMID- 8520675
TI  - Precision in capillary electrophoresis with respect to quantitative analysis of
      suramin.
AB  - Suramin is an important anti-tumor and anti-viral chemotherapeutic agent. We have
      previously presented a capillary electrophoresis (CE) method for its quantitative
      analysis, where its quantitation was linear over three orders of magnitude, with
      good precision (1.8%) and accuracy. The constantly varying electroosmotic
      properties of the capillary due to various causes such as analyte adsorption to
      the inner wall, affect the migration times of analytes during consecutive
      electrophoresis runs. This results in progressive changes in analyte peak areas,
      causing less desirable or unacceptable CE assay precision. This paper illustrates
      a strategy to overcome the problem of assay reproducibility by using an internal
      standard whose migration time is short and close to that of the analyte so that
      the relative change of migration time is minimized. Assay precisions as good as
      0.3% were observed in these experiments. These results are in agreement with the
      theoretical basis of experimental capillary electrophoresis.

PMID- 8520676
TI  - Ion-pair chromatography and micellar electrokinetic capillary chromatography in
      analyzing beta-adrenergic blocking agents from human biological fluids.
AB  - Ion-pair chromatography (IPC) and micellar electrokinetic capillary
      chromatography (MECC) were used for the separation and determination of parent
      beta-blockers from human biological fluids. In both these techniques, N-cetyl
      N,N,N-trimethylammonium bromide (CTAB) was used as a buffer additive. In IPC,
      CTAB was an ion-pair former, and in MECC it was a micelle-forming surfactant. The
      effectiveness of the IPC method using methanol-gradient elution and that of MECC
      were compared for drug-spiked serum and urine samples. Detection was performed
      with a diode-array detector in the IPC method and with a 214-nm filter in the
      MECC technique. In both methods a phosphate buffer (pH 7.0) was used. In MECC the
      buffer solution contained 10 mM CTAB, while in IPC the CTAB concentration was
      decreased from 7 to 4 mM during the separation when a methanol gradient was used.
      The study showed that the IPC technique performed better for bioanalyses than the
      high-performance MECC technique, since in MECC UV detection presented a problem
      because of the low sample concentration. However, in MECC sample preparation was
      less time-consuming, using hydrolyzation and protein precipitation and, unlike
      the IPC technique, it did not require any liquid-liquid extraction step.

PMID- 8520677
TI  - Development and validation of a bioanalytical method for the quantification of
      diltiazem and desacetyldiltiazem in plasma by capillary zone electrophoresis.
AB  - A CZE method for the quantification of diltiazem and desacetyldiltiazem in plasma
      was developed and validated. Separation was accomplished at pH 2.5 in a 0.044 M
      phosphate buffer. Sample preparation was performed by liquid-liquid extraction
      and no interferences with plasma compounds were detected. The calibration graph
      is linear over the range 5-250 ng/ml with verapamil as internal standard. The
      precision and accuracy are better than 13% at 5 ng/ml, and better than 10%
      between 10 and 250 ng/ml. The long-term reliability of the CZE system was checked
      over a 3-month period. The CZE method is a useful alternative to the already
      established HPLC method.

PMID- 8520678
TI  - Capillary electrophoresis, a rapid and sensitive method for routine analysis of
      apolipoprotein A-I in clinical samples.
AB  - A method for the determination of apolipoprotein A-I, the major protein
      compartment of HDL, in human serum is described. Rapid and easy serum sample
      preparation, well separated Apo A-I peaks in the human serum electropherogram and
      good linearity of the peak area vs. concentration plot, covering the range of the
      clinically relevant Apo A-I serum contents, suggest the introduction of this
      method routinely in clinical laboratories.

PMID- 8520679
TI  - Analysis of the components of Lycopus europaeus L. in body fluids during
      metabolism studies. Comparison of capillary electrophoresis and high-performance
      liquid chromatography.
AB  - During pharmacokinetic studies with extracts obtained from medicinally used
      plants, analysis in body fluids is mainly performed by HPLC, an established
      separation method. In this paper high-performance capillary electrophoresis
      (HPCE) is investigated for its ability to separate such complex extracts. Crude
      extracts of Lycopus europaeus L. (Lamiaceae) are traditionally used against mild
      forms of hyperthyroidism. The metabolism of a 70% ethanolic extract with respect
      to some of its individual main components (rosmarinic and caffeic acid, luteolin
      7-glucoside) and a mixture of the pure compounds were investigated using isolated
      perfused rat liver. After solid-phase extraction metabolites were determined
      using HPCE and HPLC separation techniques. A buffer solution composed of 0.05 mol
      l-1 Na2HPO4 at pH 7.0 with 30% acetonitrile was found to be the most suitable
      electrolyte for HPCE separation. The best mobile phase for isocratic HPLC was
      0.03% TFA-acetonitrile (82:18, v/v). Data obtained with HPCE are in good
      accordance with those from HPLC; HPCE, however, is clearly more rapid and simple
      to perform.

PMID- 8520680
TI  - Concentration and separation of hypoglycemic drugs using solid-phase extraction
      capillary electrophoresis.
AB  - Solid-phase extraction-capillary electrophoresis (SPE-CE) is a technique whereby
      very dilute analytes may be selectively extracted from a sample matrix and
      concentrated on-line for analysis. This study describes the first phase in the
      development of a method exploiting this technique for the direct analysis of
      hypoglycemic drugs in urine. Effective separation and detection of six
      sulfonylurea drug standards at concentrations below the detection limit of
      conventional capillary electrophoretic techniques is shown to be attainable.
      Since surfactant interfered with the on-line concentration process, non-MEKC
      (micellar electrokinetic chromatography) separation conditions were defined.
      Using 250 mM borate/5 mM phosphate at pH 8.4, all drugs in a mixture at 285 ng/ml
      were effectively extracted, concentrated from an injected volume of 2.5
      microliters, non-selectively desorbed with an organic-based elution buffer and
      electrophoretically resolved. Sample loading was found to be linear in the 0.12
      1.9 microliters range and drugs in a volume of up to 190 microliters could be
      concentrated and detected with a sensitivity of approximately 5 ng/ml. Not only
      was resolution of the desorbed material uncompromised by the presence of the SPE
      tip, but separation of glipizide and glyburide was observed despite the fact that
      these drugs were unresolved under the same separation conditions by standard
      capillary zone electrophoresis (CZE). From these results, it is clear that SPE-CE
      not only increases the sensitivity for detection but that selectivity may be
      altered due to chromatographic processes occurring on the solid-phase resin.

PMID- 8520681
TI  - Child cerebrospinal fluid analysis by capillary electrophoresis and laser-induced
      fluorescence detection.
AB  - Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was
      used to analyze a 50-microliters sample of cerebrospinal fluid from leukaemic
      children treated with high doses of methotrexate. Free amino acids and primary
      amines are labelled with fluorescein isothiocyanate prior to analysis.
      Electropherograms containing more than 50 peaks were obtained in less than 22
      min. Twenty-one peaks were identified, and 19 were quantitated. Observed
      differences in individual amino acid levels are compared with healthy reference
      values. The results indicate that CE-LIF is useful as a selective, rapid and
      sensitive tool for the determination of free amino acids and amines in clinical
      biology studies.

PMID- 8520682
TI  - Characterization of lipoprotein a by capillary zone electrophoresis.
AB  - Lipoprotein a [Lp(a)] has been recognized as a significant marker for premature
      coronary heart disease (CHD). In this paper, we present the results of Lp(a)
      analysis based on capillary zone electrophoresis (CZE). CZE separation of Lp(a)
      and its reduced species, lipoprotein a- [Lp(a-)] and apolipoprotein a [apo(a)],
      was accomplished using 50 mM borate buffer containing 3.5 mM sodium dodecyl
      sulfate (SDS) and 20% (v/v) acetonitrile (ACN). Low density lipoprotein (LDL) and
      high density lipoprotein (HDL) were separated under the same buffer conditions.
      The electrophoretic mobilities of both Lp(a) and Lp(a-) were found to be
      different from that of LDL. Benzyl alcohol (BA) and methanol (MeOH) were used as
      electroosmotic flow markers. BA molecules associated with Lp(a-) and LDL to
      enhance their UV absorbance, but did not change their effective electrophoretic
      mobilities. Our results show that CE is a very efficient and effective technique
      for lipoprotein analysis.

PMID- 8520683
TI  - Determination of polyamines in serum by high-performance capillary zone
      electrophoresis with indirect ultraviolet detection.
AB  - A method for determining polyamines in serum by capillary zone electrophoresis
      (CZE) with indirect ultraviolet detection was established. The concentrations of
      polyamines in the sera of six healthy adults were determined and the results were
      in accordance with those obtained previously by high-performance liquid
      chromatography (HPLC). However, the CZE method is superior to HPLC in that it has
      high sensitivity, small sample consumption and easy sample pretreatment.

PMID- 8520684
TI  - Application of capillary electrophoresis, high-performance liquid chromatography,
      on-line electrospray mass spectrometry and matrix-assisted laser desorption
      ionization--time of flight mass spectrometry to the characterization of single
      chain plasminogen activator.
AB  - The analysis of recombinant Desmodus salivary plasminogen activator (DSPA alpha
      1), a heterogeneous glycoprotein, is demonstrated through the use of high
      performance liquid chromatography (HPLC), high-performance capillary
      electrophoresis (HPCE), liquid chromatography-electrospray mass spectrometry (LC-
      ES-MS), and matrix-assisted laser desorption ionization--time of flight mass
      spectrometry (MALDI--TOF-MS). The proteins is analyzed at three specific levels
      of detail: the intact protein, proteolytic digests of the protein, and fractions
      from the proteolytic digest. A method for "on-column" collection of HPLC
      fractions for subsequent transfer and analysis by HPCE and MALDI--TOF-MS is
      shown.

PMID- 8520685
TI  - Rapid one-step capillary isoelectric focusing method to monitor charged
      glycoforms of recombinant human tissue-type plasminogen activator.
AB  - A rapid (< 10 min) one-step capillary isoelectric focusing (cIEF) method was
      developed to monitor charged glycoforms of recombinant human tissue-type
      plasminogen activator (rt-PA). Focusing takes place between the detector and the
      anode and the electro-osmotic flow (EOF) sweeps the separated glycoforms past the
      detector, towards the cathode. The separation uses a neutral coated capillary and
      hydroxypropylmethylcellulose (HPMC) to reduce the EOF to a constant and
      reproducible value. The method uses an ampholyte mix with a 50:50 ratio of pH 5-8
      and pH 3-10 ampholytes in 4 M urea and 0.1% HPMC to produce maximal resolution
      whilst maintaining protein solubility during focusing. The electropherograms were
      compared to isoelectric focusing (IEF) slab gels of samples of intact rt-PA. In
      both cases approximately ten charged species could be detected. Data analysis
      indicated that the intra-assay precision was < 5% for peak migration times and <
      10% for normalized peak areas. The number of charged species detected by each of
      the two methods was consistent for samples of intact rt-PA, rt-PA types I and II
      and for neuraminidase-digested rt-PA. Overall the data indicate that the
      automated cIEF method can be an adjunct to slab-gel IEF in the characterization
      and routine analysis of recombinant glycoproteins.

PMID- 8520686
TI  - Differences between natural and recombinant interleukin-2 revealed by gel
      electrophoresis and capillary electrophoresis.
AB  - High-performance capillary electrophoresis (HPCE) is shown to be useful for
      analysis of interleukin-2 (IL-2) in its native state under non-reducing
      conditions. The results obtained were compared with those from analysis of IL-2
      by protein blotting after sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) under denaturing and reducing conditions. In addition,
      resolution of the different glycosylated and non-glycosylated natural IL-2
      species was achieved by HPCE. The HPCE electropherogram of native IL-2 could
      easily generate quantitative amounts of the different naturally occurring IL-2
      species. For HPCE of IL-2 run times of less than 10 min are sufficient, and only
      extremely small amounts of IL-2 are needed. In this report, human IL-2 expressed
      in bacteria has been analysed by HPCE and the existence of two recombinant IL-2
      forms was demonstrated.

PMID- 8520687
TI  - Optimization of hapten-protein conjugation by high-performance capillary
      electrophoresis.
AB  - HPCE has been found to be efficient for the optimization of conjugation
      procedures employed for coupling of the haptens p-nitrophenyl-alpha-D
      galactopyranoside (PNPG) and soyasaponin I to a carrier protein, Kunitz soybean
      trypsin inhibitor (KSTI). The carbohydrate moieties of the haptens were oxidized
      with periodate followed by reaction with epsilon-amino groups of the carrier. For
      PNPG, the periodate oxidations (0.01-0.2 M NaIO4) were followed by HPCE and 0.1 M
      periodate was chosen as the optimum concentration. The coupling of PNPG to KSTI
      was found to proceed at a constant rate for more than 250 min. The reaction rate
      for the soyasaponin conjugation to KSTI declined after 80 min of incubation. The
      coupling of soyasaponin to KSTI was confirmed by enzyme-linked immunosorbent
      assay with monoclonal antibodies directed against soyasaponin I. The method was
      found to be particularly powerful for the investigation of conjugates with low
      epitope densities that are difficult to determine otherwise.

PMID- 8520688
TI  - Demonstration of a heparin-binding site in serum amyloid P component using
      affinity capillary electrophoresis as an adjunct technique.
AB  - Linear heparin-binding sites in the DNA- and heparin-binding serum protein
      amyloid P component were investigated using affinity capillary electrophoresis
      and reversed-phase HPLC in conjunction with affinity chromatography. Peptide
      fragments were generated from amyloid P component by treatment with Glu-C and Asp
      N endoproteinases. This peptide mixture was separated by HPLC before and after
      passage through a column of immobilized heparin. In addition, the proteolytic
      digest was separated by capillary electrophoresis in the presence of various
      amounts of heparin in solution. Migration shift patterns in the presence of
      heparin were in agreement with one of the components shown by HPLC to interact
      with immobilized heparin. The identity of this fragment was established by mass
      spectrometry after preparative HPLC and represents a novel heparin-binding
      sequence. The results illustrate the potential synergy in the combination of the
      two high-resolution separation techniques HPLC and CE. HPLC has the advantages of
      high recovery and preparative power while capillary electrophoresis is noted for
      highly efficient separations under physiological conditions. The possibility of
      using unmodified ligands in the study of biological activities of protein
      substructures while consuming very little material makes CE further attractive.

PMID- 8520689
TI  - Gas chromatographic analysis of fatty acid methyl esters.
AB  - The full process of fatty acid methyl ester (FAME) analysis consists of
      esterification of lipids, and of injection, separation, identification and
      quantitation of the FAMEs. In order for the required accuracy and precision to be
      attained, each of these steps has to be optimized. Esterification of lipids can
      be carried out with several reagents based on acid-catalysed or base-catalysed
      reactions. The advantages and disadvantages of these reagents are discussed. The
      most critical step in the gas chromatographic analysis of FAMEs is sample
      introduction. The classical split injection technique, which is the most widely
      used technique in the analysis of FAMEs, has the potential disadvantage of
      boiling-point-dependent sample discrimination. Cold injection of the sample,
      either on-column or by programmed-temperature vaporization, does not present this
      problem and should therefore be preferred. Modern, commercially available fused
      silica capillary columns offer excellent separation of FAMEs from biological
      samples. Very polar stationary phases give excellent separation of all FAMEs but
      have relatively low thermal stability, resulting in long retention times. Non
      polar phases have a much greater thermal stability but inferior selectivity. For
      many analyses, phases of intermediate polarity, which combine the advantages of a
      relatively high resolution capability with relatively high thermal stability, are
      the most suitable. FAMEs can be identified by comparison of their retention times
      with those of individual purified standards or secondary standards based on
      lipids that have been well characterized in literature. Relative retention times
      and equivalent chain-length values also provide useful information. FAMEs can be
      quantitated by peak areas via calibration factors, and absolute concentrations
      can be determined by adding an internal standard. Among numerous applications in
      biomedical research, the analysis of fatty acids from body tissues may contribute
      to the understanding of the link between the dietary intake of fatty acids and
      the diseases with which these acids are associated.

PMID- 8520691
TI  - Thin-layer chromatographic procedures for lipid separation.
AB  - This review focuses on the thin-layer chromatographic (TLC) separation aspects of
      lipid analysis. Since the space limitations do not permit, the quantitative
      aspects of the analyses are not discussed at length although some indications of
      appropriate methodology and detection reagents will be indicated. Many
      separations carried out by TLC have the prerequisite of proper sample
      preparation. Using proper sample clean-up prior to TLC enables one to carry out
      precise separation as well as sensitive quantitation. Thus, the discussions are
      divided into the two main topics--sample preparation and TLC. Examples of
      applications are limited to those which illustrate the capabilities of the
      technique as well as practicability. Since there are a number of reviews in the
      literature, the discussions herein are focused mainly on reports after 1985.

PMID- 8520690
TI  - Methods for the analysis of triacylglycerols.
AB  - This article discusses the methods most commonly employed in the analysis of the
      triacylglycerols (TAGs) in natural fats and considers the main advantages and
      disadvantages of each and the techniques for optimising analytical conditions.
      Complete analysis of the composition of a natural fat calls for a method of
      extracting and purifying the triglyceride fraction, normally by preparatory thin
      layer and column chromatography. Determination of the individual components of
      triglyceride mixtures still entails certain difficulties, namely, the separation
      and identification of the TAGs in natural fats. High-performance liquid
      chromatography (HPLC) offers significant advantages over gas and thin-layer
      chromatography. Many workers have developed non-aqueous, reversed-phase HPLC
      systems capable of successfully resolving complex mixtures of TAGs, and combining
      reversed-phase (RP) HPLC and argentation chromatography may improve the results.
      Identification of the TAGs separated by HPLC becomes an extremely complex task if
      many different fatty acids are involved and if the sn-stereoscopic positions on
      the glycerol are to be determined. Enzymatic analysis and chiral-phase
      chromatography are capable of localising fatty acids on the TAG molecule. In
      closing, some of the most interesting biomedical applications of TAG analysis are
      summarised.

PMID- 8520692
TI  - Silver ion chromatography of lipids and fatty acids.
AB  - Silver ion chromatography as applied to the analysis of lipids is reviewed. Thin
      layer, column, high-performance liquid and supercritical fluid chromatography in
      the silver ion mode are included. The lipid types covered are fatty acids,
      triacylglycerols and complex lipids. Separations are divided into those according
      to number, geometry and position of double bonds, as well as acyl positional
      isomers for triacylglycerols. The mechanism of silver ion chromatography is
      discussed in relation to recent studies using silver ion high-performance liquid
      chromatographic methodology.

PMID- 8520693
TI  - Analytical technologies for lipid oxidation products analysis.
AB  - Productive investigation of the contribution of oxidative stress to human disease
      is facilitated by the design and application of suitable analytical technologies
      for oxidation product analysis. Lipid oxidation, including polyunsaturated fatty
      acid and cholesterol oxidation, produces a variety of products that can function
      as indexes of the extent of oxidation. These products include fatty acid
      hydroperoxides and hydroxides, aldehydes, prostanoids, hydrocarbons, and
      cholesterol hydroperoxides and hydroxides, epoxides, and carbonyls. Some of these
      oxidation products have biological activities that can contribute to tissue
      damage in unique ways. This paper reviews the state-of-the-art for
      chromatographic analysis of these products through a discussion of advances that
      have taken place since 1990.

PMID- 8520694
TI  - Chromatographic techniques for the isolation and purification of lipoproteins.
AB  - Various modes of chromatography are available for lipoprotein separation. Gel
      permeation and affinity chromatography are used for preparative purposes and to
      separate lipoproteins according to size and apolipoprotein content, respectively.
      Development of rigid supports for gel permeation has led to large improvements in
      speed and resolution. Reversed-phase high-performance liquid chromatography
      (HPLC) of apolipoproteins offers the best performance in terms of speed and
      resolution of structural variants. Due to its high speed and superior resolving
      power, the recently developed technique of capillary electrophoresis should
      emerge as an important method for lipoprotein analysis.

PMID- 8520695
TI  - Quantitative chromatographic analysis of inositol phospholipids and related
      compounds.
AB  - The metabolism of phospholipids and the mobilization of second messengers such as
      inositol-1,4,5-trisphosphate, 1,2-diacylglycerol (DAG) and arachidonic acid (AA)
      from phospholipids is commonly studied by radiolabelling phospholipids with
      [3H]myo-inositol or [32P]ATP and measuring the incorporation of radioactivity in
      different phospholipids or their hydrolysis products. However, for the
      radiolabelling method to accurately reflect changes in the compound's mass, it is
      essential that the tissue is labelled to isotopic equilibrium which is difficult
      to achieve. To circumvent the disadvantages of the radiolabelling method, several
      analytical procedures have been developed for the mass analysis of phospholipids
      and inositolphosphates (IPs). Quantitation of the mass or the radiolabelling of
      phospholipids is a complex multi-step procedure that involves quantitative
      isolation of phospholipids, fractionation of individual phospholipids and either
      determination of radioactivity in each component or the measurement of their
      mass. Phospholipids, DAG and AA are extracted from tissue sample with organic
      solvents such as chloroform-methanol (2:1) containing HCl or formic acid. The
      extract is separated by TLC, cartridge-column chromatography or HPLC on a
      reversed-phase column. Phospholipids are quantitated by measuring inorganic
      phosphate, absorption at 200 nm or mass spectrometry. Inositol phosphates are
      extracted with perchloric acid or trichloroacetic acid and separated by ion
      exchange cartridge-column or HPLC with an ion-exchange column. IPs are
      quantitated by measuring inorganic phosphate or by using enzymatic reaction,
      metal-dye coupling, NMR or mass spectrometry.

PMID- 8520696
TI  - High-performance liquid chromatography of phosphatidic acid.
AB  - This paper reviews existing high-performance liquid chromatographic (HPLC)
      methods for the analysis of phosphatidic acid (PA) in various sample matrices. In
      addition to the introductory background discussion on important aspects of PA in
      lipid biochemistry, the review provides comprehensive coverage in the areas of
      derivatization techniques, detection methods, and HPLC separation techniques.
      Conversions of PA to suitable derivatives enhance the detection sensitivity and
      improve the chromatographic behavior of the analytes. Detection methods include
      the use of state-of-the-art detectors and are discussed in terms of sensitivity,
      specificity, and compatibility with analytical systems. Pertinent normal-phase
      and reversed-phase HPLC data for PA are compiled from published methods.

PMID- 8520697
TI  - Bile acid separation.
AB  - A review of the methods available for the separation of bile acids is presented,
      highlighting the most recent developments. The major chromatographic techniques
      (TLC, GC, HPLC) and combined detection systems for the determination of bile
      acids are critically evaluated and their advantages and disadvantages discussed.
      Moreover, future directions in which progress might occur are also indicated.
      Capillary GC-MS is the more established method since it provides higher
      efficiency combined with greater sensitivity and specificity and has proven
      crucial in identifying unusual bile acids. However, it requires deconjugation and
      derivatization and hence the conjugated species must be inferred from the initial
      isolation procedure. HPLC is directly amenable to the different forms of bile
      acids, but it suffers from insufficient resolving power which can be enhanced by
      exploiting the mobile-phase selectivity. The development of HPLC detection
      systems with higher sensitivity and specificity than conventional HPLC-UV is
      reported. In particular, methods for the direct coupling of HPLC to MS are
      examined with special emphasis on soft ionization processes (thermospray, fast
      atom bombardment, ion spray). Finally, the analytical potential for bile acid
      assays of more recent techniques including supercritical fluid chromatography and
      capillary electrophoresis is evaluated.

PMID- 8520698
TI  - General strategies in chromatographic analysis of lipids.
AB  - Lipid extracts of natural sources contain a large number of lipid classes and
      molecular species. Completely reproducible samples are obtained only with great
      care and skill. Analytical methods other than chromatography and/or mass
      spectrometry are of little use for resolution and identification of lipid
      molecules even in simple mixtures. The analytical information desired governs the
      selection of the chromatographic and mass spectrometric method, which determine
      the sample preparation and derivative needed. Usually a combination of
      chromatographic methods is necessary to identify specific species of lipids. The
      recent development of soft ionization techniques, that are readily interfaced
      with mass spectrometers, have greatly simplified the sample preparation and have
      largely eliminated the need for derivatization. Because these techniques require
      expensive equipment and dedicated operators, the methods selected must be
      consistent with the true analytical needs and the available resources. Although
      personal preference cannot be eliminated entirely, the general strategies
      outlined below should help to reduce the number of possibilities facing a lipid
      analyst to a few practical choices.

PMID- 8520699
TI  - High-performance liquid chromatographic analysis of corticosteroids.
AB  - This review presents recent developments in high-performance liquid
      chromatographic (HPLC) analysis of corticosteroids for the determination of
      clinically important steroids in biological specimens. Various sample preparation
      techniques are described.

PMID- 8520700
TI  - Chromatographic methods in the analysis of cholesterol and related lipids.
AB  - Methods using thin-layer chromatography, solid-phase extraction, gas
      chromatography, high-performance liquid chromatography and supercritical fluid
      chromatography are described for the analysis of single cholesterol, esterified
      and sulfated cholesterol, and for cholesterol in the context of other lipid
      components, like other sterols and lipid classes. In connection with these
      techniques several clinical applications are mentioned.

PMID- 8520701
TI  - Application of tandem mass spectrometry for the analysis of long-chain carboxylic
      acids.
AB  - The application of MS-MS for the analysis of long-chain carboxylic acids and
      their esters has proved enormously successful but expensive. It is discussed
      mainly on basis of results obtained with different instruments with lesser
      attention to principles of the method, which have been adequately reviewed
      elsewhere. The use of electrospray ionization (ESI) has greatly increased the
      sensitivity of the method and has permitted assay of total lipid extracts. The
      combination of HPLC with electrospray and single quadrupole mass spectrometry, LC
      ESI-CID-MS, rivals the triple quadrupole MS-MS application in many instances at
      considerably lower cost. However, LC-ESI-MS-MS remains the most desirable system
      at the present time for lipid ester analyses.

PMID- 8520702
TI  - Methods for urinary testosterone analysis.
AB  - Urinary testosterone analysis requires a multistep procedure to achieve a good
      degree of sensitivity and specificity in the dosage. Hydrolysis, extraction,
      purification and quantification are usually performed in sequence, and several
      options can be chosen for each of them. After introductory remarks on the
      applications of urinary testosterone measurement and a short description of the
      metabolic pathway of the hormone, an overview of the techniques most commonly
      used in each step is presented. Advantages and disadvantages of each of them are
      outlined, and a procedure for urinary testosterone analysis is suggested. The
      procedure consists of: enzymatic hydrolysis with Helix pomatia juice, followed by
      solid-phase extraction of hydrolyzed urine by a C18 cartridge coupled with an NH2
      cartridge and high-performance liquid chromatography cleanup of the extract.
      Then, quantification can be achieved by gas chromatography or radioimmunoassay.

PMID- 8520703
TI  - Chromatographic and electrophoretic analysis of biomedically important retinoids.
AB  - The determination of retinol (vitamin A) and its metabolites, as well as
      synthetic retinoids, in biological samples is a challenging task due to the
      sensitivity of these compounds to light, heat and oxygen, high protein binding,
      separation of geometric isomers and determination of low endogenous levels.
      Numerous procedures for sample preparation have been published for biological
      fluids and tissues, consisting of solvent extraction, solid-phase extraction (off
      line) and HPLC with column switching (on-line solid-phase extraction). The last
      mentioned technique has several advantages, including a high degree of
      automation, no evaporation of extraction solvents, protection from light and
      higher sensitivity. Due to the favourable UV characteristics of most retinoids,
      HPLC with UV detection is most often employed, and photodiode array detection is
      becoming more and more popular. Fluorescence and electrochemical detection have
      found only a limited field of application, but the use of LC-MS resulted in a few
      highly sensitive methods. Reconsideration of GC through the use of better
      deactivated columns and cold on-column injection and evaluation of new promising
      separation methods, such as supercritical fluid chromatography and capillary
      electrophoresis, have shown preliminary encouraging results, but appear to reach
      the required sensitivity only by coupling to MS. Therefore, HPLC with UV
      detection is still the method of choice for highly sensitive and selective
      retinoid determination, as well as for high sample throughput and robustness.

PMID- 8520704
TI  - Fatty acid profiles of lipid samples.
AB  - Most lipids are best characterized by their fatty acids which differ in chain
      length, the degree of unsaturation, configuration and position of the double
      bonds, and the presence of other functionalities. The fatty acid profiles are
      currently most frequently determined by capillary gas chromatography of the
      methyl esters which are prepared by a variety of methods. These are discussed
      with an emphasis on more recent developments, along with the stationary phases
      used for the separations and the methods employed for identification of the fatty
      acids. HPLC is applied less frequently for ascertaining fatty acid profiles than
      GC, but a very large number of derivatives for ultraviolet and fluorescence
      detection have been proposed. This method continues to evoke increasing interest,
      particularly in conjunction with fluorescence detection. This technique enables
      attainment of greater sensitivities than with standard GC methods employing flame
      ionization detection. Extensive applications of it to the analysis of free fatty
      acids in blood and other biomedical samples are clearly discernible. Other
      methods, including supercritical fluid chromatography, have found only limited
      application for fatty acid profiling.

PMID- 8520705
TI  - Use of derivatization to improve the chromatographic properties and detection
      selectivity of physiologically important carboxylic acids.
AB  - In this review, tagging techniques with reagents used for ultraviolet-visible (UV
      Vis), fluorescent (FL), chemiluminescent (CL) and electrochemical detection (ED)
      for higher carboxylic acids in HPLC are evaluated in terms of the tagging
      reactions, handling, flexibility, stability of the reagents and the corresponding
      derivatives, sensitivity and selectivity. Emphasis is given to the applications
      of these tagging techniques to biologically important carboxylic acids of
      relatively high molecular mass including free fatty acids, prostaglandins,
      leukotrienes and thromboxanes etc. Some typical examples are described. Although
      RIA and GC-MS are powerful techniques for the highly sensitive determination of
      carboxylic acids, tagging for these techniques is not included in this review
      because recent progress in tagging methods has been mainly concerned with HPLC
      detection.

PMID- 8520706
TI  - A prospective study of consumption of carotenoids in fruits and vegetables and
      decreased cardiovascular mortality in the elderly.
AB  - Recent evidence suggests that oxidative damage may be involved in atherogenesis,
      and thus dietary antioxidants, such as beta-carotene, may reduce the risks of
      cardiovascular disease (CVD). We examined the association between consumption of
      carotene-containing fruits and vegetables and CVD mortality among 1299 elderly
      Massachusetts residents who provided dietary information as a part of the
      Massachusetts Health Care Panel Study. During a mean follow-up of 4.75 years,
      there were 161 deaths attributable to CVD, 48 of which were due to myocardial
      infarction. For total CVD death and fatal myocardial infarction, risks were lower
      among those residents in the highest quartile for consumption of carotene
      containing fruits and vegetables as compared with those in the lowest. For death
      due to CVD, the relative risk (RR) was 0.54 (95% confidence interval (CI), 0.34
      to 0.86; P for trend across quartiles, 0.004). For myocardial infarction the RR
      was 0.25 (95% CI, 0.09 to 0.67; P for trend, 0.002). These observational data are
      compatible with the hypothesis that increased dietary intake of carotenoids
      decreases the risks of CVD mortality; however, confounding cannot be ruled out.
      This hypothesis requires rigorous evaluation in randomized trials of sufficient
      size to detect reliably whether carotenoids confer small-to-moderate but
      clinically important protection against CVD.

PMID- 8520707
TI  - A secondary prevention trial of antioxidant vitamins and cardiovascular disease
      in women. Rationale, design, and methods. The WACS Research Group.
AB  - The evidence for a potential benefit of antioxidant vitamins in the prevention
      and therapy of atherosclerotic disease is derived from laboratory, clinical, and
      observational epidemiologic studies but remains inconclusive. Data from
      randomized clinical trials are sparse, particularly for women. Therefore, it is
      both timely and important to conduct large-scale primary and secondary prevention
      trials of antioxidants and cardiovascular disease (CVD). The Women's Antioxidant
      and Cardiovascular Study (WACS) is a randomized, double-blind, placebo-controlled
      secondary prevention trial of the balance of benefits and risks of antioxidant
      vitamins (vitamins E and C, and beta-carotene) among 8000 women with preexisting
      CVD. This secondary prevention trial will be conducted as a companion to the
      recently started Women's Health Study, a primary prevention trial of vitamin E
      and beta-carotene, as well as aspirin. In the WACS, US female health
      professionals aged 40 years and older with a history of myocardial infarction,
      angina pectoris, coronary revascularization, stroke, transient cerebral ischemia,
      carotid endarterectomy, or peripheral artery surgery will be randomly assigned,
      utilizing a 2 x 2 x 2 factorial design, to receive vitamin E, vitamin C, beta
      carotene, and/or placebo. Cardiovascular end points include nonfatal myocardial
      infarction, nonfatal stroke, coronary revascularization procedures, and total CVD
      mortality. The present article describes the rationale, design, and methods of
      the trial.

PMID- 8520708
TI  - Methods of assessing prevalent cardiovascular disease in the Cardiovascular
      Health Study.
AB  - The objective of this article is to describe the methods of assessing
      cardiovascular conditions among older adults recruited to the Cardiovascular
      Health Study (CHS), a cohort study of risk factors for coronary disease and
      stroke. Medicare eligibility lists from four US communities were used to obtain a
      representative sample of 5201 community-dwelling elderly, who answered
      standardized questionnaires and underwent an extensive clinic examination at
      baseline. For each cardiovascular condition, self-reports were confirmed by
      components of the baseline examination or, if necessary, by a validation protocol
      that included either the review of medical records or surveys of treating
      physicians. Potential underreporting of a condition was detected either by the
      review of medical records at baseline for other self-reported conditions or,
      during prospective follow-up, by the investigation of potential incident events.
      For myocardial infarction, 75.5% of the self-reports in men and 60.6% in women
      were confirmed. Self-reported congestive heart failure was confirmed in 73.3% of
      men and 76.6% of women; stroke, in 59.6% of men and 53.8% of women; and transient
      ischemic attack, in 41.5% of men and 37.0% of women. Underreporting was also
      common. During prospective follow-up of an average of about 3 years per person,
      approximately 50% of men and 38% of women were hospitalized or investigated for
      at least one potential incident event; for each cardiovascular condition, about 1
      to 4% of those investigated during prospective follow-up were found to have had
      the cardiovascular condition prior to entry into the cohort.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8520709
TI  - Surveillance and ascertainment of cardiovascular events. The Cardiovascular
      Health Study.
AB  - While previous prospective multicenter studies have conducted cardiovascular
      disease surveillance, few have detailed the techniques relating to the
      ascertainment of and data collection for events. The Cardiovascular Health Study
      (CHS) is a population-based study of coronary heart disease and stroke in older
      adults. This article summarizes the CHS events protocol and describes the methods
      of surveillance and ascertainment of hospitalized and nonhospitalized events, the
      use of medical records and other support documents, organizational issues at the
      field center level, and the classification of events through an adjudication
      process. We present data on incidence and mortality, the classification of
      adjudicated events, and the agreement between classification by the Events
      Subcommittee and the medical records diagnostic codes. The CHS techniques are a
      successful model for complete ascertainment, investigation, and documentation of
      events in an older cohort.

PMID- 8520710
TI  - Blood lipids in Greek adolescents and their relation to diet, obesity, and
      socioeconomic factors.
AB  - A study of blood lipid levels in adolescent students in rural and urban areas of
      Greece was undertaken. Blood samples were drawn from 307 adolescents aged 12 to
      18 years attending two rural and two urban high schools of different
      socioeconomic level (urban/lower, urban/higher). Obesity among adolescents had
      statistically significant detrimental effects on the lipids profile, being
      associated with higher total and low-density-lipoprotein (LDL) cholesterol and
      lower high-density-lipoprotein (HDL) cholesterol levels. Adolescents living in
      urban areas had substantially and significantly higher levels of total and LDL
      cholesterol, but among urban residents, higher socioeconomic status was
      associated with lower levels of total and LDL cholesterol. There was no clear
      evidence that total, LDL, and HDL cholesterol levels were substantially affected
      by qualitative aspects of diet as evaluated through a food frequency
      questionnaire. The results of this study indicate that the traditional
      Mediterranean pattern of living and eating in the rural areas of Greece is
      associated with a favorable lipid profile in adolescents, which may explain the
      very low incidence of coronary heart disease (CHD) in these areas. In urban areas
      lipid profiles are satisfactory in children of high socioeconomic status but
      unfavorable in children of low- to middle-class families, which are known to be
      at higher risk for CHD.

PMID- 8520711
TI  - Assessment of ability to recall physical activity of several years ago.
AB  - In this study we assessed the reliability of recall of physical activity. Study
      participants were members of the Coronary Artery Risk Development in Young Adult
      Study (CARDIA) cohort who reported physical activity at each CARDIA examination.
      In this study, we asked 81 participants to recall activity patterns for the year
      prior to 2 to 3 years ago so that we could compare recalled activity patterns to
      those reported 2 to 3 years ago (labeled as "distantly recalled") as well as to
      activity patterns reported at the other CARDIA examinations. We found that
      distantly recalled physical activity patterns were highly correlated with those
      reported at the time of the examination where they were obtained (vigorous
      activity r = 0.84, moderate activity r = 0.64, and total activity r = 0.81).
      Distantly recalled activity was less highly associated with activity reported
      currently (vigorous activity r = 0.57, moderate activity r = 0.45, total activity
      r = 0.59). The activity recalled the best was jogging or running (r = 0.76) and
      the activity with the poorest recall was racket sports (r = 0.53). Distantly
      recalled physical activity also was related to resting pulse rate obtained during
      the time period of the recalled activity (r = -0.21). These findings suggest that
      people can recall activity patterns of several years ago with high reliability.

PMID- 8520712
TI  - A connective tissue disease screening questionnaire for population studies.
AB  - To develop a technique to screen populations for potential connective tissue
      disease (CTD), we mailed a 30-item questionnaire to 253 randomly selected
      patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma,
      polymyositis, dermatomyositis, mixed connective tissue disease (MCTD), or
      Sjogren's syndrome and to 340 randomly selected control subjects. The response
      rate after four mailings was 71% for case subjects and 54% for control subjects.
      Test-retest reliability for detection of any CTD was 0.82. Sensitivity for
      specific CTDs was 83 to 96% and specificity was 83 to 93%. The positive
      predictive value for any CTD (assuming an overall prevalence of 1.3%) was 5.5%;
      negative predictive value was 99.7%. The CTD Screening Questionnaire has high
      sensitivity and specificity for screening large populations.

PMID- 8520713
TI  - The association of reproductive and menstrual characteristics and colon and
      rectal cancer risk in Wisconsin women.
AB  - Reproductive and menstrual characteristics were ascertained by telephone
      interview from Wisconsin women with newly reported diagnoses of carcinoma of the
      colon (n = 536) and rectum (n = 243) and 2315 population control subjects. The
      relationships of parity, age at first full-term pregnancy, age at menarche,
      regularity and length of menstrual cycles, age at menopause, and type of
      menopause to colon and rectal cancer were examined. In our study population, no
      reproductive or menstrual characteristics were significantly associated with
      colon cancer, although subsite analyses suggested an increased risk for
      transverse colon cancer in women reporting irregular menstrual cycles. Only
      parity was associated with rectal cancer; women who had given birth five or more
      times were at significantly lower risk compared to those who were nulliparous
      (odds ratio: 0.60; confidence interval: 0.36, 0.99). The odds ratio per birth
      also suggested an inverse association. These data give little support to the
      hypothesis that female reproductive events modify colon and rectal cancer risk.

PMID- 8520714
TI  - Epidemiologic evidence for uterine growth factors in the pathogenesis of ovarian
      cancer.
AB  - To examine the association between ovarian cancer and prior hysterectomy or tubal
      ligation in light of various interpretations, we combined data from two
      previously conducted case-control studies of ovarian cancer. This included 450
      women with histologically verified epithelial ovarian cancer and 454 age-matched
      women from the general population for whom data on prior pelvic surgery were
      available to estimate exposure odds ratios. Overall there was a nonsignificant
      deficit of case patients who had had a hysterectomy or tubal ligation (odds ratio
      (OR) = 0.9; 95% confidence interval (CI), 0.6 to 1.3). A protective effect of
      prior hysterectomy or tubal ligation was more apparent among women who had the
      surgery 20 or more years previously (OR = 0.6; 95% Ci, 0.3 to 1.1), women who had
      not used talc in their hygiene (OR = 0.6; 95% CI, 0.4 to 1.0), and women with
      mucinous tumors of the ovary (OR = 0.3; 95% CI, 0.1 to 1.0). Although these data
      do not clearly establish the validity of or mechanisms for an association between
      prior pelvic surgery and ovarian cancer, we speculate that such an association
      exists and may be mediated through absent or reduced uterine growth factors that
      reach the ovaries through the uteroovarian circulation, with mucinous tumors most
      dependent on such factors.

PMID- 8520715
TI  - Reproductive factors and breast cancer risk. Effect of age at diagnosis.
AB  - The data from a French case-control study of 495 patients with breast cancer and
      542 control subjects interviewed in five French public hospitals, were analyzed
      to assess the effect of reproductive factors (age at menarche, age at first full
      term pregnancy, the time interval between these two ages, and parity) on the risk
      of breast cancer. Age at menarche, age at first full-term pregnancy, the time
      interval between these two ages, and parity appeared to have a limited influence
      on breast cancer risk. However, the relationship between these factors and the
      risk of breast cancer varied according to the age at breast cancer diagnosis. In
      the youngest group of women, the most consistent effects came from factors
      occurring early in life (menarche, first full-term pregnancy, and consequently
      the time interval between these two events). These factors had a null or weak
      effect on the oldest group of women. The protective effect of high parity was
      confined to the oldest group of women.

PMID- 8520716
TI  - Lifetime occupational physical activity and risk of hip fracture in women.
AB  - A case-control study was conducted to examine the effects of occupational
      activity on the risk of hip fracture in women. Only women who worked full-time or
      part-time for more than 6 months and for more than 15 h/wk since the age of 16
      were considered for study. Case patients were between the ages of 55 and 84 years
      and had a diagnosis of hip fracture in 1989 in Metropolitan Toronto (n = 331).
      Control subjects were a population-based random sample of women frequency-matched
      by 5-year age groups (n = 1002). Those who worked for 20 years or less in any
      type of job were not at a decreased risk of hip fracture (odds ratio (OR) = 0.96;
      95% confidence interval (CI), 0.70 to 1.32) compared to those who worked for more
      than 20 years in a sedentary job. However, those who worked for more than 20
      years in moderate- to heavy-activity jobs were strongly protected against hip
      fracture (OR = 0.53; 95% CI, 0.30 to 0.95). Past and recent leisure-time
      activity, estrogen use, obesity, having epilepsy, and a previous fracture were
      significant risk factors. There was no statistically significant interaction
      between occupational activity and leisure-time physical activity, suggesting that
      both types of activity are independently associated with the risk of hip
      fracture. This study showed that being employed for more than 20 years in a job
      that requires heavy activity reduces the risk of hip fracture in postmenopausal
      women.

PMID- 8520717
TI  - Trichomonas vaginalis and cervical cancer. A prospective study in China.
AB  - The relationship between Trichomonas vaginalis infection and cervical cancer was
      investigated prospectively in a cohort of 16,797 women aged 25 years or more who
      were followed from 1974 to 1985 within the framework of a cervical screening
      program in Jingan, China. Personal interviews were conducted by trained
      interviewers when the women first entered the screening program. At initial
      screening, 421 (2.51%) women had a positive cytologic diagnosis of T. vaginalis
      infection. Ninety-nine incident cases of pathologically confirmed squamous cell
      carcinoma were identified from the cohort, with a total of 140,018 person-years
      of observation. T. vaginalis infection was found to contribute to the risk of
      cervical cancer, as determined by crude estimates and after adjustment for
      potential confounding effects. In a multiple proportional hazards model, the
      relative risk for cervical cancer was 3.3 (95% confidence interval: 1.5 to 7.4)
      among women with T. vaginalis infection. Furthermore, in the multivariate
      analysis, increased risk of cervical cancer was associated with the following
      factors: number of extramarital sexual partners of both the subjects and their
      spouses, cigarette smoking, and irregular menstruation. Having a large number of
      negative Pap smears was associated with lower risk. This study suggests that
      there might be an association between T. vaginalis infection and the risk of
      cervical cancer, but only 4 to 5% of cervical cancer in Chinese women may be
      attributable to T. vaginalis infection.

PMID- 8520718
TI  - What accounts for the association of vegetables and fruits with lower incidence
      of cancers and coronary heart disease?

PMID- 8520720
TI  - Neuronal cell death in scrapie-infected mice is due to apoptosis.
AB  - Neuronal loss is a salient yet poorly understood feature in the pathology of
      transmissible spongiform encephalopathies (prion diseases). Cell culture
      experiments with neurotoxic prion protein fragments suggest that neuronal cell
      death in these diseases may be due to apoptosis. To test this hypothesis in vivo
      we used the in situ end-labeling (ISEL) technique and electron microscopy to
      study cell death in an experimental scrapie system in the mouse. ISEL, which
      relies on the incorporation of labeled nucleotides in fragmented DNA by terminal
      transferase, showed labeled nuclei in the brains and retinae of mice infected
      with the 79A strain of scrapie, whereas no labeling was observed in control
      animals. In the retina the highest numbers of labeled nuclei were found in the
      outer nuclear layer 120 days post infection followed by massive cell loss in this
      layer. In the brain, labeled nuclei were mainly found in the granular layer of
      the cerebellum of terminally ill mice. This corresponded to the presence of small
      dark nuclei with condensed and occasionally fragmented chromatin at the light and
      electron microscopical levels. Our results support the hypothesis that neuronal
      loss in spongiform encephalopathies is due to apoptosis. This may explain the
      almost complete absence of inflammatory response in prion diseases in the face of
      widespread neuronal cell death, and may also have therapeutic implications in the
      future.

PMID- 8520719
TI  - The original Gerstmann-Straussler-Scheinker family of Austria: divergent
      clinicopathological phenotypes but constant PrP genotype.
AB  - We present new data on the original Austrian kindred with Gerstmann-Straussler
      Scheinker disease (GSS) which encompasses currently 221 members in 9 generations.
      The mode of inheritance is autosomal dominant. Predominant clinical features are
      slowly progressive ataxia and late impairment of higher cerebral functions. In
      contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly
      developing dementia and severe cortical damage indistinguishable from the
      clinicopathological phenotype of Creutzfeldt-Jakob disease (CJD). PRNP codon 129
      was homozygous for methionine in both the historic and recent cases.
      Neuropathology confirms spongiosis of variable degree and numerous protease
      resistant/prion protein (PrP) amyloid plaques scattered throughout most of the
      brain as constant features in this family. Some amyloid deposits are surrounded
      by dystrophic neurites with accumulation of phosphorylated neurofilaments and
      abnormal organelles, reminiscent of Alzheimer-type plaques. Severe telencephalic
      damage and a synaptic-type fine granular immunoreactivity in laminar distribution
      in the cortex with anti-PrP after hydrated autoclaving of sections were seen only
      in the recent patient. In conclusion, factors in addition to the PRNP genotype at
      codons 102 and 129 must play a role in determining clinicopathological
      characteristics of this inherited brain amyloidosis.

PMID- 8520721
TI  - Presence of CD4+ and CD8+ T cells and expression of MHC class I and MHC class II
      antigen in horses with Borna disease virus-induced encephalitis.
AB  - Tissues from 9 horses and 1 donkey suffering from natural Borna disease were
      investigated 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. Perivascular inflammatory
      infiltrates were dominated by CD4+ T cells, whereas the majority of CD8+ T cells
      were disseminated intraparenchymally. No evidence of inflammation was found in
      the retina. Borna disease virus proteins and nucleic acids were present in the
      hippocampus, thalamus and medulla oblongata in all 10 animals, in the cerebral
      cortex, retina, trigeminal ganglion and nerve in 9, in the olfactory epithelium
      in 6 and in roots and proximal parts of large peripheral nerves in 3. No evidence
      of infection was found in the autonomic nervous system, lung, heart, liver,
      kidney or gut. BDV- proteins and nucleic acids were even more abundant in the
      trigeminal system than in the olfactory system, suggesting that infection may
      have occurred via the trigeminal nerve.

PMID- 8520722
TI  - Myelin genetics: new insight into old diseases.

PMID- 8520723
TI  - Molecular basis of common hereditary motor and sensory neuropathies in humans and
      in mouse models.
AB  - The Hereditary Motor and Sensory Neuropathies (HMSNs) are well known to be
      clinically, morphologically, and genetically heterogeneous. Yet, recent advances
      in the cellular and molecular biology of the peripheral nervous system coupled
      with remarkable progress in human and mouse genetics have provided a framework
      that has profoundly changed our understanding of the pathogenesis of these
      diseases. It now appears that most of the HMSNs are related to mutations
      affecting genes encoding Schwann cell proteins, specifically the Peripheral
      Myelin Protein PMP22, Myelin Protein Zero, and one of the gap junction proteins,
      connexin-32. Accordingly, these findings are discussed in the context of the
      clinical and pathologic features of the human HMSNs, but are interpreted in the
      context of basic research findings on the cellular and molecular biology of the
      peripheral nervous system derived from in vivo and in vitro studies in
      spontaneously-occurring and genetically engineered animal models for the HMSNs.

PMID- 8520724
TI  - The twitcher mouse: a model for Krabbe disease and for experimental therapies.
AB  - The twitcher is a naturally-occurring mouse mutant caused by an abnormality in
      the gene coded for galactosylceramidase. It is therefore genetically equivalent
      to human globoid cell leukodystrophy (Krabbe disease). Affected mice develop
      clinical symptoms at the onset of the active myelination period and, if
      untreated, die by 35 +/- days. The pathology is very similar to that in human
      disease. Toxicity of galactosylsphingosine (psychosine) that accumulates
      abnormally in the nervous system is considered to be primarily responsible for
      the pathogenesis. Transplantation of bone marrow cells from normal donors is
      partially effective and triples the life span of affected mice to 100 +/- days
      with evidence of remyelination in the CNS. The mutation responsible for the
      twitcher mutant has recently been identified. It is expected that this model will
      be useful for basic studies on treatment of this group of genetic disorders
      affecting the brain through transgenic and/or gene therapy approaches.

PMID- 8520725
TI  - Adrenoleukodystrophy: molecular genetics, pathology, and Lorenzo's oil.
AB  - Knowledge about adrenoleukodystrophy (ALD), a disorder which was described first
      in 1923, has increased greatly during recent years. The principal biochemical
      abnormality, the presumed enzyme defect, and the gene defect, have been defined.
      A dietary therapy has been proposed and attracted world-wide attention through a
      motion picture. Nevertheless, many questions remain and cannot be answered
      without a more fundamental understanding of pathology and pathogenesis. This
      article will provide a review of the history, clinical features, pathology,
      biochemistry, and the gene defect, and then appraise current efforts to clarify
      pathogenesis and develop therapeutic approaches.

PMID- 8520726
TI  - Neuropathology and genetics of Pelizaeus-Merzbacher disease.
AB  - The recent history of Pelizaeus-Merzbacher Disease (PMD) demonstrates
      paradigmatically the impact of basic biological research on clinical neurology
      and brain pathology: this rare and peculiar hereditary disease has become one of
      the best known disorders of its kind, through a cooperative research effort in
      neuropathology, human genetics, neurochemistry and molecular biology. PMD, a
      genetic dysmyelination restricted to the CNS, has been identified as a disease
      that involves the X chromosome-linked gene for myelin proteolipid protein (PLP),
      a major structural myelin component. Today more than 30 different mutations in
      this gene have been defined and associated with PMD or the clinically distinct
      form X-linked spastic paraplegia type-2 (SPG-2). Improved scanning techniques,
      specifically the non-invasive magnetic resonance imaging (MRI), allow its early
      diagnosis in the heterogeneous group of CNS myelin deficiencies. These remarkable
      achievements have, at the same time, caused a problem for disease classification.
      Myelin disorders have been grouped in the past on the basis of clinical and
      neuropathological criteria, creating a system that has now to be reconciled with
      molecular-genetic data.

PMID- 8520727
TI  - Transgenic and natural mouse models of proteolipid protein (PLP)-related
      dysmyelination and demyelination.
AB  - The X chromosome-linked PLP/DM-20 gene is the CNS myelin gene most frequently
      associated with mutations, resulting in dysmyelination in several species
      including man (Pelizaeus-Merzbacher disease, X-linked Spastic Paraplegia). The
      pathology of most PLP gene mutations is characterized by hypomyelination, glial
      cell proliferation, increased numbers of microglia, and premature oligodendrocyte
      death. In most mutants, residual myelin structures have an abnormal
      ultrastructure and periodicity. Surprisingly, transgenic mice which carry extra
      copies of the wild type PLP gene show dysmyelination, demonstrating that the PLP
      gene is dosage sensitive. Pathological changes of transgenic mice vary from the
      phenotype of natural mutants. Specifically, many Golgi saccules of
      oligodendrocytes are vacuolated and the cytoplasm contains autophagic vacuoles
      hinting at a perturbation in protein trafficking. In fact, upon transgenic
      overexpression PLP becomes a prominent peripheral myelin protein, whereas in
      normal Schwann cells PLP is restricted from entering the myelin compartment.
      Surprisingly, transgenic animals which overexpress PLP/DM-20 at a low level
      appear normal during early development, but later spontaneously demyelinate. The
      mechanisms underlying this demyelination phenotype is unknown but an immune
      mediated process has been suggested. All attempts to correct the phenotype of
      natural PLP mutants, such as jimpy mice, with a wild type transgene have had
      little effects, indicating a dominant-negative effect of the mutant gene product.
      On the other hand, mice with a targeted disruption of the PLP/DM-20 gene have
      surprisingly minor clinical signs. This suggests that the lethal phenotype
      associated with the majority of PLP gene mutations is a complex combination of
      loss and gain-of-function effects of a mutant myelin protein.

PMID- 8520728
TI  - Programmed cell death in the dysmyelinating mutants.
AB  - A large number of genetic mutants that are missing a particular myelin protein or
      that have an aberrant myelin protein composition have been described. These
      mutations usually cause dysmyelination in the PNS or CNS. Similarly, the nervous
      system of animals experimentally altered to block synthesis of myelin proteins
      have recently been generated that show aberrations in the myelin sheath. For both
      groups of animals, the numbers of myelinating cells remain relatively stable and
      glial cell death is minimal. The exception is animals with mutations in the
      proteolipid protein (PLP) gene which exhibit extensive death of oligodendrocytes
      (OLs). The degree of OL death in the PLP mutants generally correlates with the
      amount of dysmyelination. Dying OLs in the PLP mutants exhibit the classical
      features of apoptotic cells. Programmed cell death (PCD) is often, but not
      necessarily, manifested by cleavage of DNA into abundant oligonucleosomal
      fragments. Detection of these abundant DNA fragments was examined in normal and
      jimpy (jp) mice using the TUNEL (terminal deoxynucleotidyl transferase dUTP nick
      end labeling) method. In normal spinal cord and brain, at least twice as many
      cells exhibited DNA fragmentation when compared to numbers of pyknotic glia
      observed microscopically. In jp spinal cord and brain, roughly one-half of cells
      exhibited DNA fragmentation when compared to numbers of pyknotic glia observed
      microscopically. PCD of cells in normal development involving DNA fragmentation
      has been previously described and our results support that conclusion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520729
TI  - Glial transplants: an in vivo analysis of extrinsic and intrinsic determinants of
      dysmyelination in genetic variants.
AB  - Myelination in the CNS depends on the ability of oligodendrocytes (Ols) to
      efficiently colonize the brain, differentiate, and express a precise balance of
      specific genes necessary for myelin synthesis. Mutations in these genes produce
      different types of dysmyelination in animal as in human. Defects in the synthesis
      of myelin constituents usually lead to mild dysmyelinations. IN contrast,
      mutations affecting the gene encoding the proteolipid, another major protein of
      myelin, produce various perturbations of Ols biology suggesting a pleiotropic
      effect of the gene in the development of the CNS. Studies on expansion of cell
      population and survival have provided contradictory information on the extrinsic
      and intrinsic action of the gene on Ols biology. On one hand, in vitro studies
      using conditioned media as in vivo studies on heterozygotes, and transplantations
      experiments suggest that excess of programmed cell death in these mutants is
      ruled out by intrinsic factors which could act during embryonic life. On the
      other hand, attempts to compensate the gene defect by transgenic correction
      demonstrate a dominant negative effect of the jp mutation on both survival and
      functional potential of Ols. Finally, total suppression of PLP gene expression
      has a restricted effect on myelin structure without excess of cell death. These
      contradictory results are discussed in the perspective of regulation of cell
      death by competition for growth factors in limiting amount. The proposed model
      suggests that this contradiction is only apparent, and that excess of cell death
      in PLP/DM20 mutant is intrinsically determined by diminished competitivity of the
      mutant Ols for limited amounts of environmental factors.

PMID- 8520730
TI  - Glial cell transplants: experimental therapies of myelin diseases.
AB  - Transplantation of cells into the CNS of human patients with neurodegenerative
      disorders offers a radical new approach to the treatment of previously incurable
      diseases. Considerable success has been achieved in Parkinson's disease following
      transplantation of human fetal dopaminergic neurons. Disorders of myelination of
      the brain, of either inherited or acquired origin, might also be treated by glial
      cell transplantation although there are additional challenges. Cells of the
      oligodendrocyte lineage have been found to be capable of myelinating axons on
      transplantation into numerous experimental pathological environments, including
      the CNS of myelin mutants and focal areas of demyelination in normal animals made
      by injection of myelinotoxic chemicals. In general, primary cells and progenitors
      are likely to have the greatest myelinating capacity. Cell lines can also be
      used, but those driven by oncogenes may produce little myelin, and tumor
      formation is likely. Schwann cells are also a potential source of cells, possibly
      as a homograft, and may be primed by treatment ex vivo with glial growth factors.
      The variable CNS milieu seen in human myelin disease will mean that transplanted
      cells must be able to migrate appropriately and myelinate axons in an adult,
      pathological environment, and this awaits experimental confirmation.
      Physiological analysis of transplants in such situations in adult animals will
      provide the functional data which may expedite clinical trials.

PMID- 8520731
TI  - Ludwig Merzbacher (1875-1942): the man behind the disease.
AB  - Ludwig Merzbacher (1875-1942) is widely known for his seminal work on the
      pathology of the dysmyelinating CNS disease named for the clinician Friedrich
      Pelizaeus and himself. Yet his training, his scientific achievements and his list
      of publications suggest a scientist with broad interests in neuropathology,
      neuroscience, neurology and psychiatry. Among several studies in experimental and
      clinical neuropathology, Merzbacher's work on scavenger cells is the most
      outstanding. While working in Alois Alzheimer's laboratory in Munich in
      1906/1907, Ludwig Merzbacher analyzed in great detail the reaction patterns of
      these cells, which are nowadays known as reactive microglia, and already
      attempted to elucidate their function in brain pathology.

PMID- 8520732
TI  - Tissue handling in suspected Creutzfeldt-Jakob disease (CJD) and other human
      spongiform encephalopathies (prion diseases)
AB  - Despite many sensational and intimidating reports in the mass media,
      transmissible spongiform encephalopathies (prion disease) are not contagious in
      the usual sense. Successful transmission requires both specific material (an
      affected individual's tissue, from or adjacent to CNS) and specific modes (mainly
      penetrating contact with the recipient). Nevertheless, specific safety
      precautions are mandatory to avoid accidental transmission and to decontaminate
      any infectivity. Autopsy is essential for definite diagnosis of these disorders.
      Recommendations are given here for performance of the autopsy, for neuropathology
      service and appropriate decontamination; they are based on the current literature
      and on precautions taken in most laboratories with experience in handling tissue
      from transmissible spongiform encephalopathies. In particular, special care must
      be taken to avoid penetrating wounds, possible contamination should be kept to a
      minimum, and potential infectious material must be adequately decontaminated by
      specific means.

PMID- 8520733
TI  - Autoimmune phenomena in bronchial asthma with special reference to aspirin
      intolerance.
AB  - We assessed the autoimmune status of 185 adult patients with bronchial asthma and
      46 healthy subjects of similar sex and age. The patients were divided into groups
      with: (1) aspirin-induced asthma (AIA) (n = 80); (2) intrinsic asthma with good
      aspirin tolerance (n = 46); and (3) atopic asthma (n = 59). Antinuclear
      antibodies (ANA) at a titer of > or = 1:40 were present in the serum of 55% of
      the patients with AIA, 41% of those with intrinsic asthma, 39% of those with
      atopic asthma, and 11% of the healthy subjects, with the difference between each
      patient group and the healthy subjects being statistically significant (p <
      0.05). The fluorescence staining pattern of ANA on Hep-2 cells was mainly
      speckled, but the precise antigen specificity of the antibodies could not be
      identified with reference sera against extractable nuclear antigens. None of the
      subjects exhibited anti-double stranded deoxyribonucleic acid (anti-ds-DNA) or
      anti-neurtrophil cytoplasmic antibodies (ANCA). Positive ANA were associated with
      signs of complement activation, the presence of rheumatoid factor, and
      circulating immune complexes. Clinical signs of autoimmunity, evidenced by
      rheumatic symptoms, cold sensitivity, and Raynaud's phenomenon, were more common
      among the patients who tested positively for ANA. The assessment of autoimmunity
      may help in better characterizing patients with asthma and understanding various
      symptoms of the disease. Any causal relationship between asthma and autoimmunity
      remains to be established.

PMID- 8520734
TI  - Effects of intranasal administration of endothelin-1 to allergic and nonallergic
      individuals.
AB  - Endothelin-1 (ET-1), a 21 amino acid peptide, and its receptors are distributed
      in the mammalian respiratory tract. To examine the responses of human upper
      airways to ET-1, we investigated the effects of intranasal administration of ET-1
      to nine symptomatic allergic and nine nonallergic volunteers. Paper discs were
      used to administer ET-1 or diluent to one side of the nasal mucosa, and to
      collect secretions from the ipsilateral (challenged) and contralateral (opposite)
      nostrils. ET-1 (0.3-10 micrograms), but not diluent, induced dose-dependent
      bilateral increases in secretion weights, lysozyme secretion, symptoms of
      rhinorrhea and itch, and sneezing in both populations. ET-1 did not induce
      albumin secretion, histamine release, or symptoms of nasal congestion. Compared
      with the nonallergic subjects, allergic individuals sneezed more and had
      significantly higher bilateral secretion weights, contralateral lysozyme
      secretion, and symptoms of rhinorrhea following ET-1 provocation. In summary, ET
      1 induced symptoms relevant to inflammatory upper airway diseases in allergic and
      nonallergic subjects. However, responses of allergic subjects were more
      pronounced, particularly with respect to symptoms associated with neural reflex
      responses, such as sneezing and contralateral secretion. Therefore, allergic
      inflammation enhances responsiveness of the nasal mucosa to ET-1.

PMID- 8520735
TI  - Transfer of immediate hypersensitivity and airway hyperresponsiveness by IgE
      positive B cells.
AB  - The role of allergen-specific sIgE+ B cells in the development of airway
      hyperresponsiveness to electrical field stimulation was examined in a murine
      model of allergic sensitization. Ovalbumin (OVA)-specific B cells (OVA+) were
      isolated from mice that were sensitized to aerosolized OVA. The OVA+ B cell
      population was shown to be distinct from the remaining, non-OVA-responsive B
      cells (OVA-). There was a high frequency of sIgE+ B cells and a low frequency of
      sIgG+ B cells in the OVA+ population compared with the OVA- population, where the
      ratio was reversed. Although both populations produced immunoglobulin in vitro,
      only the OVA+ cells secreted anti-OVA antibodies. Transfer of 10(6) OVA+ B cells
      or as few as 5 x 10(4) OVA+/sIgE+ B cells was able to transfer the capability for
      anti-OVA IgE synthesis and cutaneous reactivity to OVA in naive recipients.
      Exposure to OVA via the airways in addition to transfer of OVA+ B cells was
      necessary for development of airway hyperresponsiveness, whereas recipients
      challenged with an irrelevant allergen, ragweed, had normal airway function.
      Transfer of up to 10(7) OVA- B cells failed to induce production of anti-OVA IgE.
      Despite production of polyclonal IgE, recipients of OVA- B cells did not develop
      airway hyperresponsiveness after OVA challenge. We conclude that both allergen
      specific IgE production and local challenge via the airways with specific
      allergen are necessary to change airway function in this model.

PMID- 8520736
TI  - Expression and function of the beta-adrenergic receptor coupled-adenylyl cyclase
      system on human airway epithelial cells.
AB  - Beta-adrenergic agonist-mediated activation of the beta receptor coupled-adenylyl
      cyclase (beta AR-AC) system expressed by human airway epithelial cells alters
      airway function. However, little is known about the magnitude of expression,
      subtype, and function of the beta receptor-adenylyl cyclase (beta AR-AC) system
      in human airway epithelial cells from healthy, nonsmoking subjects. Therefore, we
      characterized beta AR number and subtype and the cAMP response to isoproterenol
      (iso) in acutely dissociated human tracheocytes harvested from 22 healthy,
      nonsmoking adults during fibroptic bronchoscopy. Moreover, because the regulation
      of beta AR-AC system function in response to beta-agonists or inflammatory
      mediators released into the airway in asthma is poorly understood, we examined
      the cAMP response to iso after 30 min exposure of cells to iso or the protein
      kinase C activator, sn-1,2-dioctanoyl glycerol (diC8). The beta AR-AC system was
      highly expressed and functional in human airway epithelial cells. Group mean beta
      AR density (i.e., Bmax), equilibrium dissociation constant (Kd), and the
      percentage of beta 2AR subtypes assessed by radioligand binding were
      approximately 8,900 receptors/cell, 45 pM, and approximately 80%, respectively.
      Mean maximum cAMP production was approximately 42 pmol/10(5) cells, and the mean
      EC50 of the response to iso was 131 nM. However, Bmax and cAMP responses to iso
      varied considerably across subjects. For example, Bmax varied ninefold, and the
      EC50 of the cAMP response varied 39-fold interindividually. The EC50 was
      inversely related to beta AR density (r = -0.81, p < 0.05), suggesting that
      sensitivity of the cAMP response to iso was in part dependent on beta AR density.
      In all experiments, cAMP responses to iso stimulation were markedly desensitized
      in dose-dependent fashion by 30 min pretreatment with iso or diC8. For example,
      pretreatment with iso 10 microM or diC8 100 microM reduced maximum cAMP
      production to 22 and 63% of control values, respectively. These data indicate
      that: (1) the beta AR-AC system is highly expressed on acutely dissociated airway
      epithelial cells from normal adult, but beta AR expression and its functional
      coupling to adenylyl cyclase vary considerably interindividually; and (2) the
      beta AR-AC system of normal human airway epithelial cells is rapidly desensitized
      by exposure to beta-adrenergic agonists or activators of PKC.

PMID- 8520737
TI  - Peripheral airways responsiveness to cool, dry air in normal and asthmatic
      individuals.
AB  - Peripheral airways resistance (Rp) has been shown to be increased in asymptomatic
      asthmatic patients with normal spirometric values, and to be correlated with
      airways hyperresponsiveness to methacholine. We investigated whether Rp in
      asthmatic subjects with exercise-induced bronchospasm (EIB) would rise in
      response to cool, dry air. Using a wedged bronchoscope technique, we challenged
      an isolated lung segment with high flows (500 to 1,000 ml/min) of cool (22
      degrees C) dry 5% CO2 in air for 5 min in eight asthmatic subjects with EIB and
      eight normal subjects. Baseline Rp and Rp following challenge were measured with
      saturated air at 37 degrees C at a flow rate of 100 ml/min. Baseline Rp was
      significantly greater in the asthmatic (0.09; [0.05 to 0.23] cm H2O/ml/min;
      median [interquartile range]) than in the normal subjects (0.05; [0.03 to 0.07]
      cm H2O/ml/min) (p = 0.04). The asthmatic, but not the normal subjects, had a
      significant absolute maximal increase in Rp following cool, dry air (0.10 [0.03
      to 0.15] cm H2O/ml/min) (p < 0.01). In the asthmatic subjects, baseline Rp
      correlated with airways hyperresponsiveness to exercise (r = -0.76, p = 0.03). We
      conclude that the peripheral airways of asthmatic individuals with EIB are
      responsive to cool, dry air, and may play an important role in EIB.

PMID- 8520738
TI  - Glucocorticoid reduction of bronchial epithelial inflammation during
      cardiopulmonary bypass.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is released in inflammatory lung
      conditions, raising airway nitric oxide (NO) concentrations through the cytokine
      mediated induction of nitric oxide synthase (NOS). Cardiopulmonary bypass (CPB)
      creates an inflammatory state, characterized by the release of TNF-alpha, that
      may result in lung injury following CPB. This study measured plasma levels of TNF
      alpha and interleukin-6 (IL-6) as well as airway NO concentrations during CPB,
      and the effect of methylprednisolone (MPSS) on the levels of these inflammatory
      products. Twenty adult males scheduled for coronary artery bypass grafting (CABG)
      were anesthetized and randomized to a group given MPSS at 1 gm intravenously 5
      min before CPB (Group S) or a group not given MPSS (Group N). Plasma levels of
      TNF-alpha and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and
      the airway NO concentration by chemiluminescence. TNF-alpha was significantly (p
      < 0.05) increased at 30 min after the termination of CPB, while IL-6 was
      significantly (p < 0.05) increased at 50 min into CPB and 30 min after the end of
      CPB in Group N as compared with controls in the same group and with Group S at
      the same time intervals. A group of 10 patients undergoing repair of infrarenal
      aortic aneurysms, which served as a control group for plasma levels of TNF-alpha,
      showed no significant changes in TNF-alpha concentrations at any time during
      aneurysm repair. Airway NO increased significantly (p < 0.01) in Group N as
      compared with Group S at 5, 20, 35, and 50 min of CPB.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8520739
TI  - Characterization of neurogenic inflammation in the airways of two highly inbred
      rat strains.
AB  - Tachykinins released from sensory airway nerves have been shown to increase
      vascular permeability and plasma-protein extravasation (PPE) in rodent airways.
      We previously demonstrated that in Fisher (F344) rats, tachykinins cause
      bronchoconstriction mainly by indirect mechanisms involving the activation of NK1
      receptor and mast cells, whereas in the less responsive BDE rats tachykinins have
      a direct NK2 receptor-mediated effect on bronchial smooth muscle. Using Evans
      blue dye as an intravascular marker, we demonstrated that F344 rats are
      hyperresponsive for the PPE induced by substance P (SP) and capsaicin. The NK1
      receptor antagonist RP 67,580 reduced the neurogenic PPE in both strains, whereas
      the NK2 receptor antagonist SR 48,968 had no effect, indicating that only NK1
      receptors are involved in the PPE. Pretreatment with the 5-HT antagonist
      methysergide decreased the neurogenic PPE in F344 rats but not in BDE rats. In
      F344 rats depleted of mast-cell mediators with compound 48/80, the SP-induced PPE
      was significantly reduced. Pretreatment with the H1 antagonist mepyramine and the
      H2 antagonist cimetidine caused a similar reduction in SP-induced PPE in main
      bronchi of both strains. Pretreatment with atropine, indomethacin, or the
      leukotriene antagonist ICI 198,615 did not affect the SP-induced PPE. In
      conclusion, neurogenic PPE in rat airways involves the activation of NK1
      receptors. In F344 but not in BDE rats, an additional indirect mechanism
      involving 5-HT release and mast-cell activation participates in the neurogenic
      PPE.

PMID- 8520740
TI  - Mite and cat allergen levels in homes and severity of asthma.
AB  - The relationships between mite and cat allergen levels in the home, skin test
      reactivity, and severity of asthma were explored in 120 asthmatic subjects, 57 in
      Vancouver and 63 in Winnipeg. Patients in the two cities were similar in age,
      gender distribution, and severity of asthma. Skin tests were performed using 13
      common allergens, including D. pteronyssinus, D. farinae, and cat dander, as well
      as control subjects. Patients recorded their asthma symptoms, medication
      requirement, and twice daily peak expiratory flow rate for 1 yr. Dust samples
      were collected every 3 mo during each season of 1992 through 1993 in both cities.
      Mite and cat allergen levels were determined with an ELISA using monoclonal
      antibodies against Der p I, Der f I, and Fel d I. There was no relationship
      between skin test reactivity and levels of mite and cat allergens. In children
      with positive skin tests to either mite allergen, total mite (sum of Der p I and
      Der f I) allergen level was positively related to the mean daily symptom score
      and negatively related to the daily mean PEF (% of predicted). There was no such
      relationship among adult asthmatic patients with positive skin tests to either
      mite allergen. No relationship was found between cat allergen level and the
      severity of asthma.

PMID- 8520741
TI  - Thermodilution cardiac output may be incorrect in patients on venovenous
      extracorporeal lung assist.
AB  - Cardiac output measurement is part of routine monitoring in critically ill
      patients. In patients on extracorporeal lung assist, thermodilution cardiac
      output measurement may lead to erroneous results caused by indicator loss into
      the extracorporeal circuit. Seven patients on venovenous extracorporeal lung
      assist were studied using different extracorporeal blood flows. We compared
      conventional thermodilution cardiac output determinations with dye dilution
      cardiac output measurement, with dye injection into the pulmonary artery. The
      latter method is not affected by the extracorporeal circuit. The conventional
      thermodilution method overestimated cardiac output up to a maximum of 300%,
      providing results up to 10 L/min higher than true cardiac output. The mean
      difference between thermodilution and true cardiac output as determined by dye
      dilution with pulmonary artery indicator injection was 3.0 +/- 2.41 L/min. There
      was no correlation between thermodilution cardiac output values and true cardiac
      output (r = 0.06). We conclude that conventional thermodilution is not a suitable
      method for cardiac output measurement in patients on extracorporeal lung assist,
      especially if high extracorporeal blood flows are applied.

PMID- 8520742
TI  - Identification of patients with acute lung injury. Predictors of mortality.
AB  - A recent North-American-European Consensus Conference proposed new, uniform
      criteria for the definition of acute lung injury, in part to facilitate earlier
      identification of patients for clinical trials. However, these criteria have not
      been evaluated prospectively. We designed a prospective cohort study of 123
      consecutive patients with acute lung injury prospectively identified on admission
      to the adult intensive care units of a tertiary care university hospital. The
      objectives were to determine if selection of patients using the new criteria for
      acute lung injury results in a significant change in the clinical
      characteristics, risk factors, or predictors of mortality when compared with
      prior studies of patients with adult respiratory distress syndrome (ARDS); and to
      determine if a quantitative index of the severity of acute lung injury has
      prognostic value in identifying nonsurvivors of acute lung injury. We used three
      methods: (1) prospective identification of patients with acute lung injury using
      a PaO2/FIO2 ratio < 300 and bilateral infiltrates on chest radiograph in the
      absence of left heart failure; (2) evaluation of the severity of lung injury
      using a four-point scoring system; and (3) stepwise logistic regression analysis
      to identify variables significantly associated with hospital mortality. Overall
      hospital mortality was 58%. Sepsis was the most common clinical disorder (50/123
      or 41%) associated with the development of acute lung injury. Using the new
      definition for acute lung injury, 66 of the 123 patients were enrolled with a
      PaO2/FIO2 ratio between 150 and 299; 57 of the 123 patients had a PaO2/FIO2 < 150
      at the time of entry into the study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520744
TI  - Beneficial effects of the "open lung approach" with low distending pressures in
      acute respiratory distress syndrome. A prospective randomized study on mechanical
      ventilation.
AB  - Alveolar overdistention and cyclic reopening of collapsed alveoli have been
      implicated in the lung damage found in animals submitted to artificial
      ventilation. To test whether these phenomena are impairing the recovery of
      patients with acute respiratory distress syndrome (ARDS) submitted to
      conventional mechanical ventilation (MV), we evaluated the impact of a new
      ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After
      receiving pre-established levels of hemodynamic, infectious, and general care, 28
      patients with early ARDS were randomly assigned to receive either MV based on a
      new approach (NA, consisting of maintenance of end-expiratory pressures above the
      lower inflection point of the P x V curve, VT < 6 ml/kg, peak pressures < 40 cm
      H2O, permissive hypercapnia, and stepwise utilization of pressure-limited modes)
      or a conventional approach (C = conventional volume-cycled ventilation, VT = 12
      ml/kg, minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels).
      Fifteen patients were selected to receive NA, exhibiting a better evolution of
      the PaO2/FIO2 ratio (p < 0.0001) and of compliance (p = 0.0018), requiring
      shorter periods under FIO2 > 50% (p = 0.001) and a lower FIO2 at the day of death
      (p = 0.0002). After correcting for baseline imbalances in APACHE II, we observed
      a higher weaning rate in NA (p = 0.014) but not a significantly improved survival
      (overall mortality: 5/15 in NA versus 7/13 in C, p = 0.45). We concluded that the
      NA ventilatory strategy can markedly improve the lung function in patients with
      ARDS, increasing the chances of early weaning and lung recovery during mechanical
      ventilation.

PMID- 8520743
TI  - The role of intragastric acidity and stress ulcus prophylaxis on colonization and
      infection in mechanically ventilated ICU patients. A stratified, randomized,
      double-blind study of sucralfate versus antacids.
AB  - This study evaluates the effects of sucralfate and antacids on intragastric
      acidity, colonization of stomach, oropharynx and trachea, and the incidence of
      ventilator-associated pneumonia (VAP) in mechanically ventilated patients in
      intensive care units. We conducted a prospective randomized double-blind trial in
      which patients were stratified on initial gastric pH. Intragastric acidity was
      measured with computerized, continuous intragastric monitoring. The diagnosis of
      VAP was established with protected specimen brush and/or bronchoalveolar lavage.
      The study included consecutive eligible patients with mechanical ventilation and
      nasogastric tube. INTERVENTIONS: After stratification on initial intragastric pH
      into two groups, patients from both groups were randomly assigned to receive
      either antacids (a suspension of aluminum hydroxide and magnesium hydroxide), 30
      mL every 4 h, or sucralfate, 1 g every 4 h. Continuous intragastric pH monitoring
      was performed in 112 patients (58 antacids, 54 sucralfate). Using predetermined
      criteria, colonization of stomach, oropharynx, and trachea, and the incidence of
      VAP were assessed. Altogether, 141 patients were included (74 receiving antacids,
      67 sucralfate) and continuous intragastric pH monitoring was performed in 112
      patients, with a mean of 75 h per patient. The median pH and the percentage of
      time with a pH < 4.0 were calculated from each measurement. No significant
      differences in median pH values (4.7 +/- 2.2 and 4.5 +/- 2.0 for antacids and
      sucralfate, respectively) were observed. Median pH values were higher in patients
      with gastric bacterial colonization than in noncolonized patients (5.5 +/- 2.1
      and 3.3 +/- 2.0, p < 0.01), but colonization of oropharynx and trachea was not
      related to intragastric acidity. Thirty-one patients (22%) developed VAP, with a
      similar incidence in both treatment groups. In addition, antibiotic use, duration
      of hospitalization, and mortality rates were similar in both groups. Enteral
      feeding did not change intragastric acidity significantly but increased gastric
      colonization with Enterobacteriaceae, without influencing oropharyngeal and
      tracheal colonization. Antacids and sucralfate had a similar effect on
      intragastric acidity, colonization rates, and incidence of VAP. Intragastric
      acidity influenced gastric colonization but not colonization of the upper
      respiratory tract or the incidence of VAP. Therefore, it is unlikely that the
      gastropulmonary route is important for the development of VAP.

PMID- 8520745
TI  - Effects of CPAP on cardiac output in pigs with pacing-induced congestive heart
      failure.
AB  - Continuous positive airway pressure (CPAP) may improve left ventricular (LV)
      function in patients with congestive heart failure (CHF). To understand
      mechanisms involved, in nine sedated, unanesthetized pigs with pacing-induced CHF
      we measured cardiac index (CI), heart rate (HR), LV pressures and volumes,
      ejection fraction (LVEF), and maximal rate of LV pressure rise (dp/dtmax). LV end
      systolic transmural pressure (afterload) was estimated as LV end-systolic
      pressure (LVESP)-CPAP. Measurements were taken at CPAP 0, 5, 10, and 15 cm H2O
      and during recovery. At CPAP 5 cm H2O, CI increased from 4.23 +/- 1.00 to 4.99 +/
      0.88 L/min/m2 (p < 0.005), LV end-systolic volume decreased from 82.3 +/- 32.1
      to 72.7 +/- 30.3 ml (p < 0.04) and LVEF increased from 0.30 +/- 0.09 to 0.36 +/-
      0.12 (p < 0.02), and dp/dtmax increased. LVESP-CPAP was unchanged. After CPAP was
      discontinued, there was a rise in CI (p < 0.03), HR (p < 0.03), LVESP (p < 0.02),
      dp/dtmax (p < 0.02) and a decrease in total peripheral resistance (p < 0.03). We
      conclude that in CHF, low levels of CPAP improved CI, at least partly by
      improving contractility. Increased CI after discontinuing CPAP may be due to
      sympathoadrenal stimulation or withdrawal of alpha-adrenergic tone.

PMID- 8520746
TI  - Time-course of stepwise CPAP titration. Behavior of respiratory and neurological
      variables.
AB  - Because successful medical treatment of obstructive sleep apnea/hypopnea syndrome
      (SAHS) depends on adequate CPAP treatment, we have analyzed in nine SAHS patients
      the behavior of respiratory and neurological parameters during a stepwise,
      polysomnography-controlled CPAP titration to achieve an optimal CPAP.
      Particularly, we have focused on which simple variable could predict the optimal
      CPAP pressure and could better define a distinctive optimal-suboptimal pattern.
      Main parameters analyzed through the CPAP titration procedure were respiratory
      events (apnea, hypopnea), the contour of inspiratory flow, the pleural pressure
      behavior, the thoraco-abdominal motion, oximetry, arousals, and sleep stage.
      During the CPAP titration we observed: (1) a rounded shape in the inspiratory
      flow contour was associated with the lowest esophageal pressure; (2) during
      stepwise increases in CPAP, almost all apnea events changed to hypopnea periods,
      followed by prolonged periods of limited inspiratory flow with still high
      esophageal pressure but without arousals (probably suboptimal CPAP); and (3) as
      CPAP reached suboptimal levels, sleep stage moved to deeper stages without
      arousals. We conclude that if during CPAP titration the end point is the
      disappearance of arousals, most patients with SAHS will still exhibit periods of
      high intrathoracic pressures with limited inspiratory flow. Alternatively, if the
      end point to be reached is the lowest esophageal pressure, higher CPAP levels
      will be needed. The contour of inspiratory flow appears as the simplest variable
      that best correlates with lowest esophageal pressure during CPAP titration.

PMID- 8520747
TI  - Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids.
AB  - Pulmonary surfactant protein D (SP-D) is a hydrophilic glycoprotein with a
      reduced molecular mass of 43 kDa and a member of the C-type lectin superfamily,
      along with mannose-binding proteins and surfactant protein A (SP-A). We have
      recently prepared monoclonal antibodies against human SP-D and developed an
      enzyme-linked immunosorbent assay (ELISA). In this study, the levels of SP-D in
      sera and bronchoalveolar lavage (BAL) fluids of patients with lung diseases were
      determined by ELISA, using human recombinant SP-D as a standard. We demonstrated
      that the concentrations of SP-D in sera are prominently increased in patients
      with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with collagen
      disease (IPCD), and pulmonary alveolar proteinosis (PAP). Patients with IPF,
      IPCD, and PAP exhibited levels of serum SP-D 5.1-fold, 7.2-fold, and 7.0-fold,
      respectively, of those in healthy volunteers; 91.5% of the patients with IPF,
      81.3% with IPCD, and 100% with PAP exhibited serum SP-D levels that exceeded the
      cut-off value (mean + 2 SD of control value). Serum SP-D levels appeared to
      reflect the disease activity of IPF and IPCD and the disease severity of PAP.
      High levels of SP-D in BAL fluids were shown in patients with PAP, but not with
      IPF and IPCD. We conclude that measurement of SP-D in sera can provide an easily
      identifiable and useful clinical marker for the diagnosis of IPF, IPCD, and PAP,
      and can predict the disease activity of IPF and IPCD and the disease severity of
      PAP.

PMID- 8520748
TI  - Pulmonary surfactant subfractions in patients with the acute respiratory distress
      syndrome.
AB  - Changes in the surfactant system have been observed in patients with acute
      respiratory distress syndrome (ARDS). These alterations in surfactant are thought
      to contribute to lung dysfunction in this disease. In this report we describe the
      changes in surfactant subfractions in bronchoalveolar wash obtained from five
      patients with established ARDS compared with five non-ARDS patients. Our results
      show that, in addition to the changes in surfactant composition and yield
      reported previously, the ratio of small to large surfactant aggregates is
      significantly increased in patients with ARDS compared with non-ARDS patients
      (0.48 +/- 0.09 versus 0.20 +/- 0.05 respectively [p < 0.05]). This increased
      ratio was associated with a decreased level of SP-A in the large aggregate
      fraction. We suggest that this increased ratio represents a marker for surfactant
      alterations in ARDS that is independent of lavage technique and can be measured
      in a very small surfactant sample.

PMID- 8520749
TI  - The natural history of respiratory symptoms in preschool children.
AB  - We studied the natural history of preschool respiratory symptoms in a population
      based sample of children followed during the early school years. Current
      symptoms, ventilatory function, bronchial responsiveness to methacholine (BR),
      atopic status, and peak expiratory flow variability (PEFV) were assessed. Among
      those initially asymptomatic (210 subjects), 83.3% remained symptom-free, 6.7%
      started to wheeze, and 10% developed recurrent cough. Nearly half (46.9%) of the
      initial wheezing group (145 subjects) became symptom-free, 37.9% continued to
      wheeze, and 15.2% reported recurrent cough. Over half (56.0%) of the cough group
      (127 subjects) became symptom-free, 7.2% developed wheeze, and 36.8% reported
      continuing cough. Preschool wheezers showed the greatest BR (geometric mean 1.91
      mg/ml) and the highest atopic prevalence (AP) (43.6%) when compared with the
      preschool asymptomatic group (BR: 3.39 mg/ml; AP: 23.8%) and the cough group (BR:
      2.62 mg/ml; AP: 26.7%) (p = 0.0001 and p = 0.006 respectively). Children whose
      wheeze had persisted from the preschool period exhibited the poorest ventilatory
      function, the highest BR, a high AP, and high PEFV. The study shows that fewer
      than half of preschool wheezy children continued to wheeze in the early school
      years but those with persistent wheeze display many of the clinical
      characteristics consistent with a diagnosis of asthma.

PMID- 8520750
TI  - The effect of nedocromil sodium on childhood asthma during the viral season.
AB  - Viral-induced symptomatic respiratory infections (SRI) frequently cause
      exacerbations of asthma in children. This study investigated the protective
      effects of 0.5% nedocromil sodium nebulizer solution given three times a day in
      preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate
      asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or
      placebo for 24 wk during the viral season. The nedocromil sodium group was
      symptom-free 58% of the days, and the placebo-treated patients were symptom-free
      45% of the days (p = 0.027). During Weeks 1-12, significant differences favored
      nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61,
      placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo
      = 1.22; p = 0.03). Significant differences were noted during monthly intervals
      for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and
      peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p =
      0.041 Weeks 9-12). Patients in the active treatment group reduced their need for
      rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo
      demonstrated a 24% increase. There was a strong correlation between asthma
      symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the
      nedocromil sodium group demonstrated more rapid resolution of asthma symptoms
      immediately following infection (p = 0.033 summary score, p = 0.039 sleep
      difficulty). No serious adverse events were noted. Nedocromil sodium did not
      prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520751
TI  - Long-term circadian effects of salmeterol in asthmatic children treated with
      inhaled corticosteroids.
AB  - The present study was set up to investigate whether salmeterol in children with
      asthma already treated with inhaled corticosteroids (ICS) leads to a sustained
      bronchodilator effect and decreased bronchial responsiveness, both during the day
      and night. Furthermore, we investigated whether cessation of salmeterol leads to
      a rebound increase in bronchial responsiveness. Forty children with asthma (aged
      7-15 yrs) using ICS participated in a randomized, double-blind, parallel study.
      They received either twice daily 50 micrograms salmeterol or placebo. FEV1 and
      provocative concentration of methacholine that caused a 20% fall in FEV1 (PC20)
      were measured at 4:00 P.M. and 4:00 A.M. at baseline and after 16 wk. The same
      measurements were performed at 4:00 P.M. at 8 h after the first dose, and after 1
      and 8 wk. After cessation of the study drug, FEV1 and PC20 were measured at 12
      and 20 h and after 1 wk. Overall mean FEV1 from 1 to 16 wk of treatment was
      significantly higher in the salmeterol group than in the placebo group
      (difference, 4.9 +/- 2.0%, p = 0.01). Evolution in time of FEV1 did not differ
      significantly between the two groups (p = 0.09). Overall mean PC20 from 1 to 16
      wk of treatment was not significantly higher with salmeterol than with placebo
      (difference, 0.7 +/- 0.4 doubling dose [DD] p = 0.07); evolution in time of PC20
      did not differ significantly between the two groups (p = 0.58).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520752
TI  - Changes in respiratory mechanics in children undergoing cardiopulmonary bypass.
AB  - Congenital heart malformations are often associated with altered pulmonary
      hemodynamics. Lesions associated with increased pulmonary blood flow (PBF) or
      increased mean pulmonary artery pressure (MPAP) may in turn alter respiratory
      mechanics. Surgical correction of these cardiac defects frequently involves the
      use of cardiopulmonary bypass (CPB), during which the lung may be partially or
      completely atelectatic for lengthy periods, further compromising lung mechanics.
      The aims of this study were to document the effect of PBF on respiratory
      mechanics in children and to determine whether the detrimental effects of CPB
      were outweighed by the potentially positive effects of the corrective surgery.
      Twenty-three children (2-120 mo) undergoing surgery were studied while
      anesthetized, paralyzed, and mechanically ventilated. Pulmonary to systemic blood
      flow ratio was used as an index of PBF. Seventeen children had lesions associated
      with increased PBF (group 1), while six had decreased or normal PBF (group 2).
      Respiratory mechanics were measured just before the commencement of CPB and
      within approximately 2 h after the cessation of CPB, with the chest closed.
      Dynamic elastance (Ers,dyn) and resistance (RRS) were calculated from flow,
      volume (V), and pressure (Pao) measurements, using multiple linear regression
      with a volume-dependent single compartment model. Static elastance (ERS,st) was
      calculated from Pao and V measurements obtained when deflating the lung in steps
      from a maximal Pao of 30 cm H2O. ERS,dyn, ERS,st, and RRS increased significantly
      with increasing PBF to 220-330% predicted. There was no correlation between MPAP
      and respiratory mechanics. After CPB, ERS, dyn and RRS fell to normal levels in
      group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520753
TI  - The response of flow-triggered infant ventilators.
AB  - Patient-triggered ventilation (PTV) has not been feasible for infants because of
      large trigger pressures and long delay times with pressure-triggered systems.
      Recently, four infant ventilators with flow triggering have become available. We
      questioned if delay times, trigger pressures, and trigger work with these
      ventilators would be acceptable for PTV in infants. All ventilators were attached
      via 3-, 4-, and 5-mm endotracheal tubes to a spontaneously breathing infant lung
      model. The lung simulator was set at an inspiratory time of 0.65 s, tidal volume
      of 15, 30, and 45 ml, and 0 and 5 cm H2O positive end-expiratory pressure (PEEP).
      Delay time, trigger pressure, and trigger work were determined from pressure
      measured at the proximal airway, trachea, and alveolus. There were significant
      differences between the endotracheal tube sizes, sites of measurement,
      ventilatory demand and ventilator brand at each PEEP level for delay time,
      trigger pressure, and trigger work (p < 0.001). Delay time was greatest with the
      3-mm endotracheal tube at high ventilatory drive (maximum 138.2 +/- 2.1 ms). Both
      trigger pressure (minimum 0.23 +/- 0.02 cm H2O) and trigger work (minimum 0.05 +/
      0.01 g.ml) increased with decreasing endotracheal tube size, increasing
      ventilatory demand, use of PEEP, and site of measurement: alveolus > trachea >
      airway (maximum: trigger pressure 5.04 +/- 0.02 cm H2O; trigger work 114.48 +/-
      0.88 g.ml). PTV may not be appropriate under conditions of increased ventilatory
      drive and small endotracheal tube size in infants.

PMID- 8520754
TI  - Neutrophil-derived long-lived oxidants in cystic fibrosis sputum.
AB  - We evaluated long-lived oxidant potential in the sputum of patients with cystic
      fibrosis (CF) by quantitating the methionine-inhibitable, long-lived oxidant
      fraction of sputum, referred to as the chloramines. Taurine, the preferred amino
      acid substrate for chloramine formation, and myeloperoxidase (MPO), the
      chlorinated oxidant-generating enzyme, were also quantitated. As compared with
      the sputum of asthmatic subjects, the sputum of CF patients contained high
      concentrations of chloramines along with high levels of taurine and active MPO. A
      negative correlation between chloramine and taurine was found in the sputum of CF
      patients. No correlation was found between the density of Pseudomonas aeruginosa
      and the level of chloramines, taurine, or MPO. In contrast, respiratory
      parameters (%FEV or %FVC) and a nutritional index correlated positively with
      chloramine levels, whereas negative correlations were observed with taurine and
      MPO. In addition, the effect of antibiotic therapy, which significantly increased
      chloramine and decreased taurine levels, supported a beneficial effect of
      chloramines on overall clinical status. Our findings support a dual role of long
      lived oxidants at the site of airway inflammation in CF, one component of which
      is their ability to mediate oxidative stress and the other a beneficial effect
      that may be partly explained by their inhibitory effect on antiprotease defense
      systems.

PMID- 8520755
TI  - Misclassification of smoking status among Southeast Asian adult immigrants.
AB  - A total of 1,403 Southeast Asian adult immigrant males (n = 783) and females (n =
      620) from Cambodia, Laos, and Vietnam who currently resided in Central Ohio were
      interviewed to determine the self-reported smoking prevalence among them, and
      underwent biochemical confirmation of their smoking status. Variables having to
      do with the subjects' sociodemography, acculturation, and smoking history that
      were related to the misclassification of smoking status were also investigated.
      Self-reported current smoking rates were 40.9% and 5.6% for males and females,
      respectively. After verification of the subjects' smoking status by saliva
      cotinine assay (smoker status > or = 14 ng/ml), the rates of smoking were found
      to be greater, at 43.7% for males and 14.8% for females. Years of education, self
      reported smoking status, country of origin, and method of healthcare payment were
      significant predictors of misclassification. These findings suggest that the
      prevalence of smoking is higher among Southeast Asian adult females than has been
      previously reported. Variables that predict misclassification with regard to
      smoking status are presented, and their implications for clinicians and
      researchers are discussed.

PMID- 8520756
TI  - Decline in FEV1 among patients with severe hereditary alpha 1-antitrypsin
      deficiency type PiZ.
AB  - Severe alpha 1-antitrypsin (alpha 1-AT) deficiency is characterized by a decrease
      in serum alpha 1-AT to values < 20% of normal. Severe airflow obstruction, most
      commonly due to pulmonary emphysema secondary to the destruction of pulmonary
      elastic tissue, may develop at an early age in persons with alpha 1-AT
      deficiency. The purpose of this study was to estimate the annual decline in FEV1
      (delta FEV1) in alpha 1-AT-deficient patients, to compare delta FEV1 in a
      referral population (index cases) with subjects found through family studies
      (nonindex cases), and to evaluate the role of smoking cessation on delta FEV1.
      One hundred and sixty-one subjects from the Danish alpha 1-AT-deficiency study
      who were older than 25 yr and who had a recorded smoking history and at least two
      spirometric examinations 1 yr apart were studied. The delta FEV1 for each
      individual was determined by regression analysis of FEV1 on follow-up time. The
      overall mean delta FEV1 was 81 ml/yr. There was no significant difference in
      delta FEV1 between 113 index cases and 48 nonindex cases even after controlling
      for age, initial FEV1, sex, and lifetime tobacco consumption. One hundred of the
      subjects were ex-smokers, 18 had never smoked, and 43 were current smokers. The
      mean delta FEV1 among the current smokers was 132 ml/yr, versus 52 ml/yr among
      the ex-smokers (p < 0.001). For the never-smokers, the mean delta FEV1 was 86
      ml/yr.

PMID- 8520757
TI  - Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar
      lavage.
AB  - To determine the relationship between inflammatory cells in sputum,
      bronchoalveolar lavage (BAL), and bronchial mucosa, we counted the number of
      leukocytes in sputum, BAL, and bronchial biopsies obtained from subjects with
      asthma and with chronic bronchitis in stable condition or during exacerbations.
      Sputum was induced by inhalation of hypertonic saline in the asthma group.
      Spontaneous sputum was collected in the chronic bronchitis groups. Differential
      counts of leukocytes were performed on cytospin preparations of sputum and BAL.
      Eosinophils, macrophages, neutrophils, and lymphocytes were quantified in the
      submucosa of the bronchial biopsies. In asthma and in stable chronic bronchitis,
      the percentages of neutrophils were significantly higher in sputum than in BAL,
      whereas the opposite was true of the percentages of macrophages and lymphocytes.
      The lymphocyte was the predominant cell infiltrating the bronchial submucosa in
      all groups. BAL eosinophils correlated with submucosal and sputum eosinophils in
      the asthma and exacerbated chronic bronchitis groups. A similar trend was
      observed between submucosal and sputum eosinophils. In conclusion, the relative
      proportion of inflammatory cells was different in sputum, BAL, and bronchial
      mucosa. However, there was a fairly good agreement between the number of
      eosinophils counted with the three techniques in asthmatics and in exacerbated
      chronic bronchitics, suggesting that sputum cell analysis may be used for a
      noninvasive assessment of airway eosinophilia.

PMID- 8520758
TI  - Associations of PM10 and airborne iron with respiratory health of adults living
      near a steel factory.
AB  - The association between daily PM10 (particles with a median aerodynamic diameter
      of < or = 10 microns) and iron particle concentrations and respiratory health was
      studied in a population of adults selected for current or recent bronchodilator
      use. Acute changes in respiratory health were measured as changes in peak
      expiratory flow (PEF), and daily prevalence of respiratory symptoms and
      medication use as recorded in a diary. The study period was October 11 through
      December 22, 1993. The study population included 32 adults living near a large
      steel industry in Wijk aan Zee, the Netherlands. During the study period, 24-h
      average PM10 concentrations in Wijk aan Zee ranged from 36 to 137 micrograms/m3
      while the 24-h average concentrations of iron, silicon, sodium, and manganese
      ranged from approximately zero to 6.95, 1.84, 12.02, and 0.37 micrograms/m3
      respectively. The steel industry was found to contribute significantly to the
      PM10 concentrations, and especially to the iron and manganese concentrations in
      the air. The association of changes in respiratory health with changes in PM10,
      iron, sodium, and silicon was evaluated using a time series approach. A
      statistically significant decrease in PEF was found to be associated with
      increasing PM10 concentrations. Stronger associations were found for smokers than
      for nonsmokers, and for subjects reporting many chronic respiratory symptoms than
      for subjects reporting few such symptoms. Increased concentrations of iron tended
      to be associated with a decline in PEF, with a lag of 2 to 3 d, although the
      association did not reach statistical significance.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8520759
TI  - Low-dose nebulized morphine does not improve exercise in interstitial lung
      disease.
AB  - Recent reports have suggested that low-dose nebulized morphine may improve
      exercise tolerance in patients with interstitial lung disease (ILD) by acting on
      peripheral opioid-sensitive pulmonary receptors. We therefore examined whether
      the administration of low-dose nebulized morphine would influence dyspnea or the
      breathing pattern during exercise of subjects with ILD and improve their exercise
      performance. Each of six subjects with ILD underwent three maximal incremental
      cycle ergometer tests, each test separated from the last by at least 3 d. Each
      exercise test was similar except that 30 min before exercise, the subjects
      received nebulized saline (control), morphine 2.5 mg, or morphine 5.0 mg,
      respectively, in double-blinded fashion. No significant differences were noted in
      exercise duration, maximal workload, or sense of dyspnea at the end of exercise
      in the control test and the tests with either morphine 2.5 mg or morphine 5.0 mg.
      Nor were significant differences noted in resting, submaximal, or end-exercise
      measurements of oxygen uptake (VO2), carbon dioxide output (VCO2), end-tidal CO2
      (PETCO2), oxygen saturation (SaO2), minute ventilation (VI), respiratory
      frequency (f), tidal volume (VT), or heart rate (HR) in the three tests. Low-dose
      nebulized morphine did not alter the subjects' breathing pattern or affect the
      relationship between dyspnea and ventilation during exercise. No significant side
      effects were noted. The administration of low-dose nebulized morphine to subjects
      with ILD neither relieves their dyspnea during exercise nor improves their
      maximal exercise performance.

PMID- 8520760
TI  - Sleep-disordered breathing in African-American elderly.
AB  - Although sleep-disordered breathing (SDB) has been shown to be very prevalent in
      the elderly, little has been done to examine differences between the elderly of
      different racial groups. It has been well documented that SDB often results in
      hypertension and that hypertension is more common in African-Americans than in
      Caucasians. Therefore, one might suspect that SDB might be more common in African
      Americans. Caucasians (n = 346) and African-Americans (n = 54) older than 65 yr
      of age were studied. African-Americans reported less satisfaction with sleep (p =
      0.017), more difficulty falling asleep (p < 0.001), more daytime sleepiness (p =
      0.0014), and more frequent morning headaches (p = 0.0043). African-Americans
      napped 0.8 times more frequently per evening (p = 0.05) and 11 min longer per nap
      (p = 0.019) than did Caucasians, and they showed a trend toward more total sleep
      time (428 versus 408 min). Of greater interest was the fact that more African
      Americans had severe SDB with a relative risk twofold as great (relative risk =
      2.13) as that for Caucasians, which was confirmed in a logistic regression
      analysis where race was associated with the presence of SDB (RDI > or = 30)
      independently of age, sex, and body mass index. The mean RDI for those African
      Americans with severe SDB was significantly higher than that for Caucasians (72.1
      versus 43.3; p = 0.014).

PMID- 8520761
TI  - Hypocapnia and increased ventilatory responsiveness in patients with idiopathic
      central sleep apnea.
AB  - We previously demonstrated that central apneas during sleep in patients with
      idiopathic central sleep apnea (ICSA) are triggered by abrupt hyperventilation.
      In addition, baseline PCO2 at the time of augmented breaths which triggered
      central apneas was lower than for augmented breaths which did not trigger apneas.
      These observations led us to hypothesize that patients with ICSA chronically
      hyperventilate maintaining their PCO2 close to the threshold for apnea during
      sleep owing to increased chemical respiratory drive. To test these hypotheses, we
      recorded transcutaneous PCO2 (PtcCO2) during overnight sleep studies on nine
      consecutive patients with ICSA and nine sex-, age-, and body-mass-index-matched
      control subjects. Daytime PaCO2 as well as rebreathing and single breath
      ventilatory responses to CO2 were also measured. Compared with the control
      subjects, the patients had significantly lower mean PtcCO2 during sleep (37.8 +/-
      1.2 versus 42.7 +/- 10.9 mm Hg, p < 0.01) and lower PaCO2 while awake (35.1 +/-
      1.3 versus 38.8 +/- 0.9 mm Hg, p < 0.05). Furthermore, patients with ICSA had
      significantly higher ventilatory responses to CO2 for both the rebreathing (3.14
      +/- 0.34 versus 1.60 +/- 0.32 L/min/mm Hg, p < 0.005) and single breath methods
      (0.51 +/- 0.10 versus 0.25 +/- 0.04 L/min/mm Hg, p < 0.05). We conclude that: (1)
      patients with ICSA chronically hyperventilate awake and asleep and (2) chronic
      hyperventilation is probably related to augmented central and peripheral
      respiratory drive which predisposes to respiratory control system instability.

PMID- 8520762
TI  - Is normobaric simulation of hypobaric hypoxia accurate in chronic airflow
      limitation?
AB  - Hypobaric hypoxemia is experienced by passengers during commercial aircraft
      flight. In order to assess the extent of hypoxemia and to test whether hypobaric
      hypoxia can be accurately estimated at sea level, the results of the normobaric
      hypoxia altitude simulation test (N-HAST) were compared with those of the
      hypobaric hypoxia altitude simulation test (H-HAST) in six normal control
      subjects and nine patients with chronic airflow limitation (CAL) at simulated
      cabin altitudes of 6,000 ft (1,829 m) and both at rest and during exercise at
      8,000 ft (2,438 m). Serial arterial blood samples were drawn during the breathing
      of 15.1 and 16.3% inspired oxygen at sea level (N-HAST) at rest and during light
      exercise, and during the breathing of room air at simulated cabin altitudes (H
      HAST) of 609 mm Hg (6,000 ft) and 565 mm Hg (8,000 ft) at rest and during light
      exercise. As measured with the H-HAST technique, the mean (+/- SD) PaO2 of the
      normal group fell from 96.2 +/- 6.2 mm Hg (sea level) to 70.1 +/- 6.0 mm Hg
      (6,000 ft), and to 61.7 +/- 1.6 mm Hg (8,000 ft at rest) and 54.8 +/- 7.1 mm Hg
      (8,000 ft during exercise) (p < 0.005 by analysis of variance [ANOVA]). In the
      CAL group, the mean (+/- SD) PaO2 fell from 75.8 +/- 8.2 mm Hg (sea level) to
      57.0 +/- 6.3 mm Hg (6,000 ft), and 49.5 +/- 6.1 mm Hg (8,000 ft at rest), and
      38.6 +/- 7.5 mm Hg (8,000 ft during exercise) (p < 0.005 by ANOVA).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520763
TI  - Prenatal cocaine alters diaphragmatic EMG responses to hypoxia in developing
      swine.
AB  - To distinguish pure effects of prenatal cocaine exposure on respiratory control
      from confounding factors inherent to drug abuse, a porcine model was established.
      Cocaine was administered at 2 mg/kg 4 times daily during 0.66-1.0 gestation to 5
      paired sows. At birth, cocaine-exposed piglets were fostered to the unexposed
      paired sows and their litters. Respiratory measures were obtained from
      diaphragmatic electromyographic activity (EMGDI) of 3 to 9 (young) and 21 to 31
      (older) day-old, chronically instrumented piglets during 10 min each of normoxia
      and hypoxia (10% O2 in 90% N2), and compared between cocaine-exposed and
      unexposed animals. Arterial pH and gas tensions in hypoxia were not altered by
      cocaine. In the young neonates, only during hypoxia, cocaine preexposure produced
      a transient elevation of the peak and initial slope of the integrated EMGDI
      envelope, but did not affect respiratory timing, provided no extensive periodic
      breathing or apnea had occurred. In the older animals, during hypoxia only,
      cocaine preexposure increased the peak and initial slope of EMGDI envelope while
      decreasing summed EMGDI activity, EMGDI duration and Ttot toward levels seen in
      the young unexposed neonates. These findings suggest that prenatal exposure to
      cocaine retards the normal maturation of respiratory EMG responses to hypoxia.

PMID- 8520764
TI  - Interrelationship of breath components in neighboring breaths of normal eupneic
      subjects.
AB  - To determine the fraction of variational activity that is correlated on a breath
      to-breath basis from uncorrelated random fluctuations, we performed
      autocorrelation analysis in 33 normal subjects during resting breathing. A
      calibrated inductive plethysmograph was used to nonobtrusively record 700 breaths
      in each subject. The group mean autocorrelation coefficients at a lag of 1 breath
      for each of the three primary breath components, tidal volume (VT), inspiratory
      time (TI), and expiratory time (TE), were significantly different from zero (p <
      0.001). The autocorrelation coefficients for VT, 0.295 +/- 0.148 (SD), and TE,
      0.259 +/- 0.121, were greater than that for TI, 0.201 +/- 0.135 (p < 0.001 and p
      < 0.01, respectively). The autocorrelation coefficients for each breath component
      remained significant for approximately 3 consecutive breaths (p < 0.001),
      indicating the presence of "short-term memory." Cross-correlation analysis
      revealed significant interrelationships (p < 0.001) for all component
      irrespective of which component was leading or following, with the exception of
      the pairing of VT in the leading breath and TI in the subsequent breath. In
      conclusion, in resting healthy subjects breath components display considerable
      breath-to-breath variability that is not completely random in nature, but which,
      instead, has a significant fraction of structured correlated variational
      activity.

PMID- 8520765
TI  - Rapid diagnosis of pleural tuberculosis by polymerase chain reaction.
AB  - We have investigated the use of polymerase chain reaction (PCR) for the rapid
      diagnosis of pleural tuberculosis. The study was composed of 21 patients with
      pleural tuberculosis, confirmed by culture or pleural biopsy, and 86 control
      subjects. The PCR assay was based on detecting a 123-bp DNA segment belonging to
      the insertion sequence IS6110, specific of Mycobacterium tuberculosis complex. In
      21 patients diagnosed with pleural tuberculosis, Ziehl-Neelsen staining was
      positive in three (14%) (95% CI, 7 to 21%) and pleural fluid culture in 11 (52%)
      (95% CI, 43 to 61%). Pleural biopsy revealed granulomas with caseous necrosis in
      72%, and the culture was positive in 67% of the patients. Adenosine deaminase
      activity determination was positive (> 45 IU/L) in 86% (95% CI, 79 to 93%). The
      sensitivity and specificity for PCR was 81% (95% CI, 74 to 88%) and 100% (95% CI,
      95 to 100%), respectively. All culture-positive specimens were PCR positive. We
      conclude that PCR is a rapid, sensitive, and specific method for the diagnosis of
      pleural tuberculosis. However, further prospective studies are required to
      properly evaluate the yield of the technique.

PMID- 8520767
TI  - Measuring ventilation of patient care areas in hospitals. Description of a new
      protocol.
AB  - It has been recommended that ventilation of health care facilities should be
      monitored regularly to reduce the risk of nosocomial transmission of
      tuberculosis. We developed a simple method to measure air-change rates and
      direction of airflow in patient care areas. Pure carbon dioxide (CO2) was
      released at 13.5 L/min for 5 min, then measured for 30 min within the room and
      outside in the hallway. Smoke tubes were also used to measure direction of
      airflow. Doors and windows (if openable) were manipulated. This protocol, when
      conducted in five offices in 30 patients care areas in two hospitals, provided
      good mixing and reproducible decay curves, with less than 15% coefficient of
      variation for repeated measures over a wide range of air-change rates.
      Manipulation of door and/or window produced significant changes in air-change
      rates and airflow direction, although calculated air-change rates were more
      variable. Smoke tube measurements were inconsistent, agreed poorly with evidence
      of CO2 movement from room to hall, and were strongly affected by room to hallway
      temperature differentials. CO2 release and measurement proved to be a simple, yet
      reliable, method to measure air-change rates and the effect of door or window
      manipulation. Smoke tube measurements were not reliable to characterize direction
      of airflow.

PMID- 8520766
TI  - Bronchoscopic or blind sampling techniques for the diagnosis of ventilator
      associated pneumonia.
AB  - The purpose of this prospective postmortem study was to assess the diagnostic
      accuracy of bronchoscopic techniques (bronchoalveolar lavage [BAL] and protected
      specimen brush [PSB]) and nonbronchoscopic techniques (blind bronchial sampling
      [BBS] and mini-BAL) in the diagnosis of ventilator-associated pneumonia (VAP).
      The results of each technique were compared with histology and culture of lung
      tissue specimens obtained by surgical pneumonectomies in 38 patients who died
      after at least 72 h of mechanical ventilation. Histology was positive for VAP in
      18 patients and negative in 20 patients. There were 12 definite VAP (positive
      histology and positive lung cultures) and 6 histologic VAP (positive histology
      and negative cultures). Clinical pulmonary infection score (CPIS) at a threshold
      of 6 achieved a sensitivity of 72% and a specificity of 85%. When the CPIS was
      combined with the logarithmic concentration of the predominant microorganism
      obtained from the BBS sample culture, specificity was increased to 95%, for a
      threshold of 10. Using 10(3) cfu/ml as the threshold of positivity for cultures
      obtained with PSB and mini-BAL samples and 10(4) cfu/ml for cultures obtained
      with BBS and BAL, the respective sensitivities of these techniques for definite
      VAP were 42, 67, 83, and 58%. The sensitivity of BBS was significantly higher
      than that of PSB (p < 0.05). The area under the receiver operator characteristic
      curve was significantly greater for BBS than PSB (p < 0.05). Given that it is
      more sensitive and noninvasive, BBS is preferable to PSB for the diagnosis of
      VAP.

PMID- 8520768
TI  - Impaired natural immunity to pneumolysin during human immunodeficiency virus
      infection in the United States and Africa.
AB  - Human immunodeficiency virus (HIV) infection is associated with a significantly
      increased incidence of pneumococcal pneumonia and concomitant bacteremia. We
      hypothesized that the predisposition of HIV-infected patients to invasive
      pneumococcal infection may be related, in part, to an impaired immune response to
      the pneumococcal antigen pneumolysin (PLY) because PLY facilitates bacterial
      invasion. We measured serum anti-PLY antibodies in two separate populations of
      HIV-infected and HIV-seronegative controls, using both an enzyme-linked
      immunosorbent assay method and a functional assay of antibody inhibition of PLY
      induced hemolysis and cytotoxicity. HIV-infected patients in the United States
      had significantly lower titers of anti-PLY antibodies by both methods than did
      seronegative control subjects. Moreover, HIV-infected patients in Kenya who later
      developed pneumococcal bacteremia also had significantly lower anti-PLY antibody
      levels at baseline compared with seronegative control subjects. We conclude that
      lower baseline levels of antibodies to PLY are associated with the higher
      incidence of bacteremic pneumococcal infections among HIV-infected patients.

PMID- 8520769
TI  - The impact of exercise reconditioning on breathlessness in severe chronic airflow
      limitation.
AB  - Exercise in chronic airflow limitation (CAL) is often limited by symptoms before
      the physiologic boundaries of maximal ventilatory or cardiovascular capacities
      are attained. Symptom amelioration should translate directly into improved
      exercise performance. We studied the impact of a 6-wk supervised multimodality
      endurance exercise program (EXT) on perceived breathlessness (B) and leg effort
      (LE) and sought a physiologic rationale for symptom improvement. Thirty patients
      with CAL (FEV1/FVC = 42 +/- 2%, mean +/- SEM) were tested before and after EXT.
      Their responses were compared with those of a matched control group (n = 30;
      FEV1/FVC = 44 +/- 2%) after a nonintervention period. Testing included pulmonary
      function tests, chronic dyspnea evaluation (Baseline/Transition Dyspnea Index
      [BDI/TDI]), and graded cycle exercise with cardioventilatory monitoring and Borg
      scaling of B and LE. Spirometry did not change (delta) post-EXT. EXT
      significantly (p < 0.001) reduced chronic breathlessness (TDI = +2.8 +/- 0.3)
      compared with control (TDI = 0.0 +/- 0.3). Exertional symptoms of B and LE also
      fell (p < 0.01) after EXT (slopes of B and LE relative to VO2 fell by 14 and 23%,
      respectively; delta B/VO2 was associated with delta LE/VO2, r = 0.52, p < 0.01).
      Post-EXT slopes of B over ventilation (VE) also decreased by 10% (p < 0.025).
      Total cycle work increased 142 +/- 70% (p < 0.001) post-EXT and correlated
      primarily with delta B/VO2 (r = -0.64, p < 0.001). The best correlate of delta
      B/VO2 was delta VE/VO2 (r = 0.47, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520770
TI  - Distribution of pulmonary capillary transit times.
AB  - The length of time that blood remains in the pulmonary capillary is an important
      variable in gas exchange. We have investigated the distribution of capillary
      transit times in isolated rabbit lungs perfused with a bicarbonate-free buffer.
      The time course of gas exchange was monitored by enclosing the lungs in a
      plethysmograph. A bolus of buffer containing dissolved acetylene was injected
      into the perfusion system. Exchange of this inert gas occurred as soon as the
      bolus reached the capillary bed, thereby describing the input function into the
      bed. A separate bolus injection of bicarbonate solution resulted in production
      and excretion of CO2 as long as the bolus remained in the capillary bed. The rate
      of CO2 production was adjusted by partial inhibition of endothelial carbonic
      anhydrase. The distribution of capillary transit times was computed from a model
      of CO2 production in the capillary bed and the observed rates and volumes of
      acetylene and carbon dioxide excretion. The recovered distributions indicate that
      there is a fairly wide distribution of capillary transit times (relative
      dispersion, 0.45) around the mean value of 1.71 s (+/- 0.53 [SD]). Only 10% of
      capillary transit times are less than one half of mean transit time. It is likely
      that gas exchange reaches equilibrium in the capillary bed except possibly during
      strenuous exercise or exposure to high altitude or in disease.

PMID- 8520771
TI  - Muscle strength, symptom intensity, and exercise capacity in patients with
      cardiorespiratory disorders.
AB  - The contribution of muscle strength to symptom intensity and work capacity was
      examined in normal individuals and patients with cardiorespiratory disorders.
      Respiratory muscle strengths (maximal inspiratory and expiratory pressures) and
      peripheral muscle strengths (leg extension, leg flexion, seated bench press, and
      seated row) were measured in 4,617 subjects referred for clinical exercise
      testing. Subjects then rated the intensity of leg effort, discomfort with
      breathing (dyspnea), and chest pain (Borg scale) during an incremental exercise
      task (100 kpm/min each minute) to capacity on a cycle ergometer. Subjects were
      classified into groups on the basis of pulmonary function, drug therapy for
      cardiac disorders, and the presence of chest pain during exercise with
      electrocardiographic changes indicative of myocardial ischemia. Respiratory and
      peripheral muscle strengths, normalized for differences in age, sex, and height,
      were significantly reduced in patients with cardiorespiratory disorders compared
      with normal individuals. Muscle strength was a significant contributor to symptom
      intensity and work capacity in both health and disease; a two-fold increase in
      muscle strength was associated with a 25 to 30% decrease in the intensity of both
      leg effort and dyspnea and a 1.4- to 1.6-fold increase in work capacity. These
      results emphasize the need for an integrative approach in the assessment and
      therapeutic management of exercise intolerance, which considers the contribution
      of muscle weakness to excessive symptoms and reduced work capacity, in addition
      to the contribution of ventilatory, gas exchange, and circulatory impairments.

PMID- 8520772
TI  - Quality of well-being predicts survival in lung transplantation candidates.
AB  - Predictors of survival were evaluated among 74 patients selected for a lung
      transplantation program. Each patient received the quality of well-being scale, a
      utility-based outcome measure that gives a score on a continuum ranging from 0
      (for dead) to 1.0 (for optimum function), and a measure of depressive symptoms
      (Beck depression inventory). Over the course of follow-up, 24 patients died
      (ranging from listing date, 3 to 1, 110 d). Of the 49 patients who received lung
      transplantation, 13 died. In a multivariate analysis, the most significant
      predictor of survival was quality of well-being (relative risk = 0.454, p <
      0.05). Lung transplant status, when entered as a time-dependent covariate (a
      function of how long the patient waited for surgery) was not a significant
      predictor of survival (relative risk = 0.942, p > 0.05). Depression was not a
      significant predictor of survival (relative risk = 0.961, p > 0.05). We conclude
      that health-related quality of life is a significant predictor of survival for
      patients with serious lung diseases.

PMID- 8520773
TI  - The importance of bronchoscopy with transbronchial biopsy and bronchoalveolar
      lavage in the management of lung transplant recipients.
AB  - Medical and surgical advances have made lung transplantation a feasible therapy
      for end-stage lung disease. Fiberoptic bronchoscopy with bronchoalveolar lavage
      (BAL) and transbronchial lung biopsy (TBBx) is an accepted technique for
      detecting clinically evident rejection and infection in the allograft of
      symptomatic recipients. The role of TBBx and BAL in managing asymptomatic
      recipients is less defined. We retrospectively examined the role of bronchoscopy
      with TBBx and BAL in 1124 bronchoscopy procedures that were performed on 161 lung
      transplant recipients between January 1, 1988, and December 31, 1993.
      Bronchoscopy was performed when there was a change in the recipient's clinical
      condition, to assess the response of the allograft to a prior therapy, and under
      a surveillance protocol for detecting asymptomatic rejection or infection.
      Surveillance bronchoscopy was performed according to the following schedule: 10
      14 days after transplantation, every 3 mo during the first year, every 4 mo
      during the second year, and at 6-mo intervals thereafter. Surveillance
      bronchoscopies were defined as procedures where the physician felt that there was
      no infection or rejection in the allograft on the basis of a standardized
      clinical evaluation, which excluded the results of the TBBx and BAL. We compared
      the clinical impression recorded by the physician on the day of the procedure
      with the final diagnosis determined after the results of the TBBx and BAL were
      known. We found unsuspected rejection and/or infection that required therapy in
      25% (90/355) of all surveillance bronchoscopy procedures. Most episodes (61/90,
      68%) of unsuspected rejection and/or infection occurred in the first 6 mo after
      transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520774
TI  - Pulmonary function changes in lung-cancer patients treated with radiation with or
      without carboplatin.
AB  - In order to examine changes in pulmonary function in patients with locally
      advanced non-small-cell lung cancer (NSCLC) before, during, and after standard
      radiotherapy or combined chemoradiotherapy, we conducted a prospective study
      involving patients with such cancer, who were treated with radiation alone or
      with concurrent radiation and carboplatin from October 1992 to February 1994 at
      the University Hospital in Groningen, the Netherlands. Thirty-five patients were
      treated. Two patients were excluded because of pulmonary emphysema. Pretreatment
      values of TLC, VC, the gas-transfer coefficient (Kco), the pulmonary diffusing
      membrane factor (Dm), and pulmonary capillary blood volume (Vcap) were lower than
      in normal subjects and patients with chemotherapy-naive germ-cell carcinoma who
      had a similar pulmonary tumor load as the result of hematogenous metastases. The
      NSCLC patients' reduced Kco was explained by a decrease in Dm, a measure of
      alveolar-capillary membrane disturbance, and a similar decrease in Vcap.
      Pretreatment TLC did not correlate with Vcap or Dm, indicating extra- rather than
      intrapulmonary vascular and lymphatic obstruction as an explanation for the
      reduced Vcap and Dm. Locally advanced NSCLC was treated with radiation (n = 16)
      or combined continuous carboplatin infusion and radiation (n = 17). No changes in
      TLC, VC, Kco, Dm, or Vcap were observed during and 2 wk after the end of either
      treatment, nor were any differences in pulmonary function observed with the two
      treatments, indicating an absence of additional acute pulmonary toxicity caused
      by continuously infused carboplatin in this patient group.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8520775
TI  - Lymphocyte subsets of the nasal mucosa in perennial allergic rhinitis.
AB  - T cells have been considered to play a primary role in IgE-mediated atopic
      diseases, yet little is known about the T-cell subsets in the nasal mucosa of
      patients with perennial allergic rhinitis. To elucidate the characteristics of T
      cells at the site of allergic inflammation, we analyzed the proportions,
      phenotypes, stages of differentiation, and distribution of T-cell subsets in the
      nasal mucosa of 15 patients with house-dust-mite perennial allergic rhinitis
      (PAR) and 14 patients with chronic infective rhinitis (CIR), using flow cytometry
      and immunohistochemistry. We also examined the T-cell subsets in the peripheral
      blood (PBL) in conjunction with those of the nasal mucosa in 10 patients with PAR
      and in nine patients with CIR. Our results revealed no obvious difference in the
      percentage of nasal CD3+ T cells, CD8+ T cells, and alpha beta T cells in the PAR
      and CIR patients. In contrast, CD4+ T cells (p < 0.05), CD3+4-8- double-negative
      T cells, (p < 0.01), and gamma delta T cells (p < 0.01) were significantly
      increased in the nasal mucosa of PAR patients. A majority of the CD4+ T cells in
      the nasal mucosa of PAR patients coexpressed the CD45RO surface molecule, and a
      predominant proportion of CD4+ T cells in the nasal coexpressed the CD45RO
      surface molecule, and a predominant proportion of CD4+ T cells in the nasal
      epithelium were CD45RO+. The ratio of CD4+ CD45RO+:CD4+ CD45RA+ T cells in the
      allergic patients' nasal mucosa was significantly greater than that in autologous
      peripheral blood (p < 0.01). The proportion and stages of activation and
      differentiation of T-cell subsets in the allergic patients' nasal mucosa were
      independent of those in the peripheral blood. An increase in the proportion of
      natural killer (NK) cells was observed in the nasal mucosa of CIR patients. Taken
      together, our results suggest that nasal T cells exhibit distinct patterns of
      distribution, differentiation, and activation in different inflammatory
      conditions of the nose. PAR is characterized by a selective increase in CD4+
      memory T cells, CD3+4-8- double-negative T cells, B cells, and gamma delta T
      cells in the nasal mucosa. The increase in CD4+ memory T cells in the allergic
      nasal epithelium may have critical implications in the pathogenesis of PAR.

PMID- 8520776
TI  - Interleukin-13 expression in the nasal mucosa of perennial allergic rhinitis.
AB  - Allergic rhinitis is an IgE mediated atopic disease characterized by elevated
      levels of allergen specific IgE antibodies that play a central role in mediating
      allergic reactions. Interleukin 13 (IL-13) is a novel T-cell-derived cytokine
      that shares several functional properties with IL-4 and has been demonstrated to
      be capable of inducing IgE synthesis. The present study was designed to
      investigate the expression of IL-13 gene in the epithelial compartment of the
      nasal mucosa of patients with perennial allergic rhinitis (PAR) to house dust
      mite, comparing it with that in the nasal epithelial compartment of chronic
      infectious rhinitis (CIR) patients and normal volunteers (NV). We also
      investigated the IL-13 gene expression in the peripheral blood of PAR patients.
      Nasal scrapings were collected from the inferior turbinate of patients undergoing
      conchotomy surgery and from outpatients, and the mRNA expression of IL-13 was
      analyzed by the RT-PCR method. Peripheral blood mononuclear cells were isolated
      by density-gradient centrifugation and the expression of IL-13 gene was examined
      by the RT-PCR method. IL-13 expression at protein level and its cell source were
      analyzed by immunohistochemistry of inferior turbinate biopsies. The levels of
      total serum IgE and allergen-specific IgE antibodies in the serum were estimated
      by the PRIST and CAP RAST method, respectively. IL-13 gene expression was
      detected in the epithelial compartment of the nasal mucosa of 18/19 PAR patients
      but was undetected in normal volunteers and CIR patients.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8520777
TI  - Abnormal intraepithelial airway nerves in persistent unexplained cough?
AB  - Idiopathic persistent nonproductive cough (PNPC) is characterized by enhanced
      cough sensitivity to inhaled capsaicin, suggesting that capsaicin-sensitive
      afferent airway nerves are either present in increased numbers or functionally
      upregulated. In 16 patients with idiopathic PNPC and eight healthy control
      subjects, we measured cough sensitivity to inhaled capsaicin and the anatomic
      density in bronchial epithelium of nerves immunoreactive for the general nerve
      marker protein gene product (PGP)-9.5 and the sensory neuropeptides calcitonin
      gene-related-peptide (CGRP) and substance-P (SP). The log concentrations of
      capsaicin required to elicit at least two (C2) and five (C5) coughs were
      significantly lower in patients (P) than in control subjects (C) (median [range]
      log C2, P = 0.3 [-0.3 to 1.2] microM; C = 1.5 [0.9 to 2.1], p < 0.0005; log C5, P
      = 0.8 [-0.3 to 2.1]; C = 2.6 [1.8 to 3.0], p < 0.0005). In bronchial epithelium
      taken from the carina of the right upper lobe (RUL) and a subsegmental carina of
      the right lower lobe (RLL), total nerve density (PGP-9.5 immunoreactivity) was
      greater in P than C, although this was not significant. CGRP-immunoreactive nerve
      density was significantly higher in P than in C in the RUL (median [range] P =
      1.05% [0.13 to 5.08]; C = 0.02% [0 to 0.24], p = 0.001) and RLL (P = 0.59% [0.04
      to 3.14]; C = 0% [0 to 0.50], p < 0.02). SP-immunoreactive nerves were not
      significantly different in the two groups. Abnormal intraepithelial airway nerves
      containing increased quantities of CGRP are present in patients with idiopathic
      PNPC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520778
TI  - Tryptase inhibitors block allergen-induced airway and inflammatory responses in
      allergic sheep.
AB  - Tryptase, a mast cell serine protease, has been implicated in the pathophysiology
      of allergic asthma, but formal evidence to support this hypothesis has been
      limited by the lack of specific inhibitors for use in vivo. Therefore, in this
      study we examined the effects of two inhibitors of tryptase, APC 366 [N-(1
      hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride] and BABIM [bis(5
      amidino-2-benzimidazolyl)methane] on antigen-induced early and late responses,
      airway responsiveness as measured by carbachol provocation, microvascular
      permeability as measured by bronchoalveolar lavage (BAL) albumin concentrations,
      and tissue eosinophilia from biopsies in allergic sheep. APC 366 and BABIM were
      administered by aerosol in all experiments. In vehicle control trials, antigen
      challenge resulted in peak early and late increases in specific lung resistance
      (SRL) of (mean +/- SE, n = 6) 259 +/- 30% and 183 +/- 27% over baseline,
      respectively. Treatment with APC 366 (9 mg/3 ml H2O given 0.5 h before, 4 h
      after, and 24 h after antigen challenge) slightly reduced the peak early response
      (194 +/- 41%), but significantly inhibited the late response (38 +/- 6%, p < 0.05
      versus control trials). Twenty-four hours after challenge, APC 366 also
      completely blocked the antigen-induced airway hyperresponsiveness to inhaled
      carbachol observed in the control trial.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520779
TI  - Localization of platelet-derived growth factor and insulin-like growth factor I
      in the fibrotic lung.
AB  - To better understand the mechanisms responsible for the increase in numbers of
      fibroblasts and increased collagen synthesis in fibrotic intestitial lung
      diseases, platelet-derived growth factor (PDGF)-A and PDGF-B, PDGF receptor-alpha
      and -beta, insulin-like growth factor I (IGF-I), and IGF-I receptor were
      evaluated immunohistochemically. Additionally, the messenger ribonucleic acids
      (mRNAs) for PDGF-A and PDGF-B, PDGF receptor-alpha and -beta, and IGF-I were
      investigated by in situ hybridization in alveolar macrophages and lung tissues
      from patients with interstitial lung disease. In specimens of bronchoalveolar
      lavage fluid (BALF), PDGF-A, PDGF-B, and IGF-I were local in alveolar macrophages
      in patients with idiopathic pulmonary fibrosis (IPF), patients with sarcoidosis
      (Sar), and normal individuals. Although there were no differences between IPF and
      Sar in terms of the staining intensity or number of positive cells, the number of
      such cells was smaller in the normal controls. In lung tissues with early-stage
      IPF, PDGF and IGF-I proteins were localized exclusively in alveolar macrophages,
      mononuclear phagocytes, fibroblasts, alveolar Type II cells, vascular endothelial
      cells, and vascular smooth-muscle cells. In lung tissues with late-stage IPF and
      those from normal controls, only alveolar macrophages contained PDGF and IGF-I
      proteins. Interestingly, the cellular localizations of PDGF receptor-alpha and 
      beta, and of IGF-I receptor were the same as those of the PDGF and IGF-I proteins
      in early-stage IPF, whereas these cells were not positive for any of these
      substances in late-stage IPF or normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520780
TI  - Mediastinal staging of non-small-cell lung cancer with positron emission
      tomography.
AB  - To determine the usefulness of positron emission tomography with fluoro-2
      deoxyglucose (PET-FDG) in assessing mediastinal disease in patients with non
      small-cell lung cancer (NSCLC) and to compare its yield to that of computed
      tomography (CT), we performed a prospective consecutive sample investigation in a
      university hospital and its related clinics. In 30 patients with NSCLC with
      clinical stage I (T1-2, NO, MO) disease, we compared the results of chest CT and
      PET-FDG with the findings at surgical exploration of the mediastinum. Seven (77%)
      of nine patients with surgically proven mediastinal metastasis were identified by
      the PET-FDG results, with four false-positives in 21 patients with negative lymph
      node dissections (p = 0.004). Using the results of pathologic examination of
      mediastinal lymph nodes as the criterion standard, the diagnostic sensitivity,
      specificity, accuracy, positive predictive value (PPV), and negative predictive
      value (NPV) for PET-FDG imaging of mediastinal metastases were 78%, 81%, 80%,
      64%, and 89%, respectively. The sensitivity, specificity, accuracy, PPV, and NPV
      for chest CT in the detection of mediastinal metastasis were 56%, 86%, 77%, 63%,
      and 87%, respectively. CT and PET-FDG results agreed in 21 patients. The
      diagnostic accuracy of the combined imaging modalities was 90%. We concluded that
      mediastinal uptake of FDG correlates with the extent of mediastinal involvement
      of NSCLC and may contribute to preoperative staging. PET-FDG imaging complements
      chest CT in the noninvasive evaluation of NSCLC, and strategies for its use merit
      further investigation.

PMID- 8520781
TI  - Effect of chronic antigen and beta 2 agonist exposure on airway remodeling in
      guinea pigs.
AB  - We recently reported that chronic exposure to fenoterol (FEN) in guinea pigs
      increases in vivo and in vitro airway responsiveness to a degree similar to that
      induced by chronic antigen (ovalbumin [OA]) exposure. We hypothesized that these
      changes were due to airway inflammation and airway remodeling. To trace newly
      recruited granulocytes as a marker of inflammation and to detect DNA replication
      in resident airway wall cells, the nucleotide 5'-bromo-2'-deoxyuridine (BrdU) was
      administered intermittently over the six-wk period of chronic FEN and/or OA
      exposure. Noncartilaginous airway dimensions were measured and the area fraction
      of BrdU-immunoreactive and total nuclei in adventitia, smooth muscle, and
      epithelium was determined by immunohistochemistry and point counting. The
      proliferation index was defined as the ratio of the two area fractions in each
      wall area. The adventitial areas of FEN- and OA-treated airways were respectively
      62 and 88% greater than those of control airways (p < 0.05). The inner wall areas
      were not increased. The smooth muscle cell and epithelial cell proliferation
      index was increased after OA (smooth muscle index: control, 2.7 +/- 1.1% [SEM];
      OA, 23.0 +/- 3.7%; p < 0.02) but not after FEN exposure, and there was an
      increased number of BrdU-immunoreactive granulocytes in the adventitia and
      epithelium after OA but not after FEN exposure. The increased in vivo airways
      responsiveness produced by chronic OA or FEN exposure may be attributable to
      adventitial thickening and increased in vitro muscle contractility, but the
      cellular mechanisms underlying these and other airway wall responses are
      different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520782
TI  - Contribution of endothelin-1 to warm ischemia/reperfusion injury of the rat lung.
AB  - The purpose of the present study was to clarify the role of endothelin-1 (ET-1)
      in the pathogenesis of ischemia/reperfusion lung injury and to determine whether
      pretreatment with an ET receptor antagonist prevents such injury. The left lung
      of Sprague-Dawley rats was subjected to 60 min of no-flow warm ischemia followed
      by 90 min of reperfusion. The plasma ET-1 concentration increased significantly
      after reperfusion compared with before and after ischemia (p < 0.05). Arterial
      oxygen tension was reduced, and the lung tissue wet/dry weight ratio increased in
      post-reperfusion lungs compared with both pre-ischemia and post-ischemia lungs.
      Histologic study showed pulmonary edema, hemorrhage, hyaline membrane formation,
      and a significant increase in lung tissue neutrophils after reperfusion. In
      addition, the expression of ET-1 mRNA was determined by Northern blot analysis.
      Although ischemia did not significantly alter ET-1 expression, reperfusion
      increased expression in the left lung markedly and in the right lung moderately.
      Pre-infusion of FR139317, an ETA receptor antagonist, prevented post-reperfusion
      damage to the lung. These results suggest that ET-1 contributes to the
      ischemia/reperfusion injury of the rat lung, mediated by an ETA receptor, and
      that an ETA receptor antagonist may inhibit ischemia/reperfusion lung injury.

PMID- 8520784
TI  - Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is
      prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan.
AB  - In contrast to the fact that alpha 1-antitrypsin (alpha 1-AT) deficiency is one
      of the most common hereditary disorders of Caucasians, deficient variants among
      Orientals have been recognized to be extremely rare. Only 12 cases of alpha 1-AT
      deficiency have been reported in Japan, including five cases in which the genetic
      defects have already been elucidated: Mnichinan (delta Phe52[TTC] and Gly148[GGG]
      ->Arg148[AGG]), two unrelated cases of Siiyama (Ser53[TCC]-->Phe53[TTC]), a
      heterozygote of Mmalton (delta Phe52[TTC]), and one additional case of 14q-
      syndrome (sporadic deletion of the neighboring region of the alpha 1-AT gene
      locus). alpha 1-AT Siiyama is a deficient variant originally identified in a 38
      yr-old patient with pulmonary emphysema in Japan. The amino acid substitution in
      this variant occurs in a highly conserved residue of the serpin (serine protease
      inhibitor) backbone (Seyama K, et al. 1991. J. Biol. Chem. 266:12627-12632). We
      attempted to determine whether alpha 1-AT deficiency in Japan was caused by
      independent genetic defects or whether it shared some common mutations in the
      alpha 1-AT gene. We examined five of seven available families for which the
      genetic defects causing alpha 1-AT deficiency have not yet been explored. When
      the allele-specific polymerase chain reaction (PCR) was performed with a pair of
      oligonucleotide primers having the mutated base sequence of the alpha 1-AT
      Siiyama allele at the 3' end, all eight cases of alpha 1-AT deficiency among five
      unrelated families turned out to be homozygous carriers of the alpha 1-AT Siiyama
      mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520783
TI  - Inflammatory cytokines in cystic fibrosis lungs.
AB  - Chronic pulmonary infection with Pseudomonas aeruginosa continues to be the major
      cause of morbidity and mortality in cystic fibrosis (CF). Several characteristics
      of CF, including the excessive influx of neutrophils into the airways, cachexia,
      and hyperglobulinemia, could reflect the effects of cytokines, such as
      interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor (TNF-alpha). We
      hypothesized that these pro-inflammatory cytokines, produced by alveolar
      macrophages in response to pseudomonas and/or other microorganisms, promote the
      destructive inflammatory process in the lung. We evaluated bronchoalveolar lavage
      (BAL) fluid and BAL macrophages from 22 CF patients and 13 healthy control (HC)
      subjects, measuring soluble TNF-alpha, IL-1 beta, IL-6, and IL-8 and the
      regulatory molecules TNF soluble receptor (TNF-sR), IL-1 receptor antagonist (IL
      1Ra), and IL-10 (cytokine synthesis inhibitory factor). Levels of the
      proinflammatory cytokines were higher in CF versus HC BAL (p < or = 0.05 for IL
      1, TNF, and IL-8; p = 0.06 for IL-6). In contrast, HC BAL contained significantly
      more IL-10 than CF BAL (p < 0.05), but TNF-sR and IL-1Ra were similar.
      Immunocytochemistry demonstrated a higher percentage of CF than control BAL
      macrophages expressing intracellular cytokines (p < 0.05). Thus, enhanced
      macrophage production of proinflammatory cytokines and decreased production of
      the regulatory molecule IL-10 may have important roles in the pathogenesis of CF
      lung disease.

PMID- 8520785
TI  - Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical
      emphysema.
AB  - In an attempt to further evaluate the role of neutrophil elastase (NE) in the
      development of emphysema, we examined the immunologic quantity of NE bound to
      alpha 1-protease inhibitor (PI), the NE inhibitory activity, and the molecular
      pattern of alpha 1-PI in unconcentrated bronchoalveolar lavage fluid (BALF)
      supernatant from 36 community-based older volunteers. They were classified into
      three groups: 10 current smokers with low attenuation areas (LAAs) on the lung
      computed tomography (CT) scans who were considered to have subclinical emphysema,
      13 current smokers who had a comparable smoking history but no LAA, and 13
      noncurrent smokers without LAA. The concentration of NE-alpha 1-PI complex was
      significantly increased in the subjects with subclinical emphysema when compared
      not only with the noncurrent smokers (0.52 +/- 0.10 versus 0.21 +/- 0.03 SEM
      micrograms/mg albumin, p < 0.01) but also with the LAA(-) current smokers (0.52
      +/- 0.10 versus 0.23 +/- 0.07 SEM micrograms/mg albumin, p < 0.01). NE inhibitory
      activity measured by a spectrophotometric method using methoxysuccinyl-alanyl
      alanyl-prolyl-valyl-paranitroanilide did not show any significant difference
      between the two groups of current smokers. There was no difference in the pattern
      or density of native and proteolysed alpha 1-PI bands between the three groups by
      Western blotting. We conclude that NE-alpha 1-PI complex in BALF is a factor that
      may differentiate smokers who are potentially developing emphysema from those who
      are not.

PMID- 8520786
TI  - Identification and localization of immunoglobulin binding factor in
      bronchoalveolar lavage fluid from healthy smokers.
AB  - Immunoglobulin binding factor (IgBF), which is abundant in human seminal plasma,
      is known to bind immunoglobulin, interact with anti-Fc gamma RIII antibodies, and
      block pokeweed mitogen (PWM)-stimulated lymphocyte blastogenesis. In this study,
      we investigated whether IgBF is present in the lower respiratory tract, whose
      secretions come into contact with the external environment. For this, IgBF was
      measured in brochoalveolar lavage fluid (BALF) from 42 healthy normal subjects
      (23 nonsmokers and 19 smokers) by enzyme-linked immunosorbent assay (ELISA). IgBF
      was detected in BALF from these normal subjects, and its level was significantly
      higher in BALF from smokers (127.2 +/- 98.7 ng/ml versus 23.3 +/- 20.7 ng/ml). On
      gel filtration chromatography of BALF, IgBF was eluted in a region corresponding
      to a molecular weight of 27 kD. Western blot testing with a monoclonal antibody
      to IgBF indicated that IgBF in BALF had a molecular weight of 27 kD under
      nonreducing conditions and of 16 kD under reducing conditions. Thus, the
      migration pattern of IgBF in BALF corresponded to that of IgBF in seminal plasma.
      IgBF immunoreactivity was detected histochemically in mucus glands and goblet
      cells in the lower respiratory tract. These results demonstrate that IgBF is
      present in the lower respiratory tract, and that smoking may cause its increased
      production in this region.

PMID- 8520787
TI  - How common are renal angiomyolipomas in patients with pulmonary
      lymphangiomyomatosis?
AB  - Pulmonary lymphangiomyomatosis has been associated with renal angiomyolipoma in
      case reports, but the prevalence of this association has not been well
      documented. The objective of this study was to determine the frequency of renal
      angiomyolipoma in a series of subjects with pulmonary lymphangiomyomatosis.
      Eighteen consecutive patients with pulmonary lymphangiomyomatosis were seen at a
      single institution between 1989 and 1994. Of these, one patient was excluded
      because she did not have an abdominal computed tomographic (CT) scan. We found
      eight out of 17 (47%) patients with pulmonary lymphangiomyomatosis to have renal
      angiomyolipomas. These were found either at surgery or on abdominal CT scanning.
      Thus, renal angiomyolipomas occur commonly in association with pulmonary
      lymphangiomyomatosis. Consequently, the early detection of renal angiomyolipoma
      by abdominal CT may be important, because lesions with dimensions larger than 4
      cm may present an increased risk for complications related to tumor growth or
      hemorrhage. Serial follow-up by ultrasonography or CT scanning is important in
      identifying and monitoring high-risk patients. Prophylactic treatment (partial or
      total nephrectomy) may be considered for patients with tumors that show
      significant growth or other complications, such as hemorrhage.

PMID- 8520788
TI  - Increased susceptibility to silicosis and TNF-alpha production in C57BL/6J mice.
AB  - Toxic oxygen species and several proinflammatory cytokines are involved in the
      pathogenesis of silicosis. In order to understand whether factors that lead to
      susceptibility to ozone are also important in silicosis or not, we examined ozone
      sensitive C57BL/6J mice and ozone-resistant C3H/HeJ mice as models of silicosis.
      We also analyzed the production of proinflammatory cytokines in both the acute
      and the chronic phases. On Day 2 after silica injection, the ozone-resistant
      C3H/HeJ mice showed significantly higher cellular responses as recognized by
      bronchoalveolar lavage (BAL) cell counts than did the C57BL/6J mice. In the
      chronic phase (Day 28 after silica injection), the ozone-sensitive C57BL/6J mice
      showed significantly greater responses to instilled silica judged by total
      protein and cell number in BAL fluid, hydroxyproline content, and histology than
      the ozone-resistant C3H/HeJ mice. TNF-alpha production by BAL cells after silica
      exposure was significantly higher in C57BL/6J mice than in C3H/HeJ mice in the
      chronic phase, whereas there was no significant difference in IL-1 alpha
      production between both strains of silica-injected mice. Also, the control
      C57BL/6J mice had significantly higher secretions of TNF-alpha than did the
      control C3H/HeJ mice in the acute phase. These results suggest that ozone
      sensitive C57BL/6J mice are also more susceptible to silicosis than are ozone
      resistant C3H/HeJ mice, and that the initial lower cellular responses and
      increase in TNF-alpha production may be related to the higher level of
      inflammatory and fibrotic response in the C57BL/6J mice.

PMID- 8520789
TI  - Neutrophil-induced lung protection and injury are dependent on the amount of
      Pseudomonas aeruginosa administered via airways in guinea pigs.
AB  - We investigated the roles of neutrophils in mediating both the protective effect
      against bacterial infection and the harmful effect of lung injury induced after
      the intratracheal instillation of live bacteria. We examined the mortality rate,
      lung injury, and bacterial clearance following the intratracheal instillation of
      Pseudomonas aeruginosa in low (10(4) colony-forming units [CFU]) and high doses
      (10(8) CFU) in normal (control) guinea pigs, others made neutropenic with
      cyclophosphamide (CPA), and guinea pigs made neutrophilic with recombinant
      granulocyte colony-stimulating factor (rG-CSF). Lung injury was assessed by the
      ratio of the concentration of 125I-labeled albumin in lung tissue to that in
      plasma (T/P) and the animals' lung weight-to-body weight (LW/BW) ratio. With
      10(4) CFU, the CPA group showed an increased T/P ratio of 0.22 +/- 0.03 versus
      0.14 +/- 0.01 in the control and 0.11 +/- 0.01 (mean +/- SEM) in the rG-CSF
      groups (p < 0.01). Viable bacteria were recovered from bronchoalveolar lavage
      fluid (BALF) in the CPA group. Neutrophil recruitment was observed in the lungs
      of animals in the control and rG-CSF groups. With 10(8) CFU, the mortality rate
      was increased in the rG-CSF group (7 of 10) as compared with the control (0 of 9)
      and CPA groups (1 of 9) (p < 0.05), which reflected an increased LW/BW (g/kg)
      ratio (16 +/- 2 versus 12 +/- 1) in the CPA group (p < 0.05). We conclude that
      neutrophils protect against lung injury during low-level bacterial challenge, but
      enhance lung injury and contribute to mortality during high-level bacterial
      challenge.

PMID- 8520790
TI  - Tumor angiogenesis correlates with histologic type and metastasis in non-small
      cell lung cancer.
AB  - This study investigated the clinico-pathologic correlation of tumor angiogenesis
      in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical
      specimens of 55 consecutive patients with primary non-small-cell lung cancers
      were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas.
      Twenty-five patients had stage I disease, eight patients had stage II disease,
      and 22 patients had stage IIIA or IIIB disease. Among them, 28 had nodal
      metastasis and 27 did not. The microvessel was demonstrated by immunocytochemical
      staining for factor VIII and platelet endothelial cell adhesion molecules (PECAM
      1). The microvessels in the areas of highest neovascularization were counted
      under light microscopy in 200x field by two independent observers without
      knowledge of clinical information. At least three separate fields were counted
      for each specimen. The Mann-Whitney U test was used for statistical analysis. The
      microvessel counts in adenocarcinoma were significantly higher than in the
      squamous cell carcinoma (54.4 +/- 35.65 versus 26.16 +/- 20.46 in factor VIII
      staining and 80.52 +/- 48.42 versus 40.04 +/- 32.33 in PECAM-1 staining; p <
      0.001). The microvessel counts in patients with Stages I-II disease were
      significantly lower than that of stages IIIA-IIIB disease (23.63 +/- 16.21 versus
      65.36 +/- 31.92 in factor VIII staining and 41.85 +/- 36.76 versus 93.00 +/-
      43.08 in PECAM-1; p < 0.001). Patients with nodal metastasis had higher
      microvessel density than those without nodal metastasis (56.67 +/- 35.55 versus
      23.44 +/- 15.77 in factor VIII staining and 86.89 +/- 46.46 versus 36.30 +/-
      25.83 in PECAM-1 staining; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520791
TI  - Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during
      idiopathic pulmonary fibrosis. Possible role of transforming growth factor beta
      and tumor necrosis factor alpha.
AB  - Pulmonary biopsy specimens from ten cases of idiopathic pulmonary fibrosis (IPF)
      were examined using routine histological stains, including toluidine blue, and
      immunohistochemistry by means of specific antibodies against alpha-smooth muscle
      (alpha-SM) actin, desmin, keratin, TGF beta 1, and TNF alpha. The sections were
      compared with two cases of normal lung. As shown previously, normal alveolar
      interstitium did not contain alpha-SM actin positive myofibroblasts nor did the
      alveolar lining contain any significant number of TGF beta 1 or TNF alpha laden
      epithelial cells. In IPF, during the inflammatory stage, the alveolar
      myofibroblasts expressed alpha-SM actin and the regenerating type II alveolar
      epithelium staining strongly with TGF beta 1 and TNF alpha antibodies. The former
      cytokine was also detected in the interstitial matrix and fibroblastic cells as
      well as in the wall of vessels. At this stage, a manifest mast cell infiltration
      was noted. In very fibrotic and cystic alveolar tissue, i.e., at end stage
      fibrosis, the number of alpha-SM actin positive myofibroblasts as well as that of
      TNF alpha laden type II epithelial cells diminished, while TGF beta 1 positive
      cells persisted. Our findings demonstrate that during IPF alveolar type II
      epithelium constitutes, if not the site of synthesis, at least the main reservoir
      for TGF beta 1 and TNF alpha. These cytokines, besides their involvement in
      fibrogenesis, play probably an important role in the expression of alpha-SM actin
      by alveolar myofibroblasts. Our study suggests the possibility of an interaction
      between interstitial cells and alveolar epithelium, during IPF.

PMID- 8520792
TI  - Eosinophilic pneumonia and respiratory failure associated with a trazodone
      overdose.
AB  - Drug-induced eosinophilic lung disease commonly presents as a simple pulmonary
      eosinophilia-like syndrome consisting of transient pulmonary infiltrates,
      peripheral eosinophilia, and mild pulmonary symptoms that disappear promptly upon
      withdrawal of the offending medication. However, a more fulminant presentation
      most resembling acute eosinophilic pneumonia has been recently described. We
      present a patient with BAL-confirmed eosinophilic pneumonia (EP) and respiratory
      failure after a trazodone overdose. This is the first case of EP associated with
      trazodone and only the third drug-mediated EP reported to precipitate respiratory
      failure.

PMID- 8520793
TI  - Effect of acute and chronic inhaled furosemide on bronchial hyperresponsiveness
      in mild asthma.
AB  - We determined whether chronic administration of furosemide aerosol would be
      beneficial for the treatment of asthma. First, we showed that furosemide aerosol
      delivered from a metered-dose inhaler (10 and 20 mg) significantly protected
      against sodium metabisulfite (MBS) challenge by 0.6 and 1.3 doubling dilutions
      respectively in 12 volunteers with mild asthma. In a double-blind cross-over
      study, we examined the effect of furosemide aerosol from a twice more efficient
      metered-dose inhaler (10 mg four times per day) inhaled over 4 wk versus placebo
      in 12 other asthmatic subjects. There was no significant effect of furosemide on
      bronchial responsiveness to methacholine or MBS. Treatment with furosemide over 1
      mo did not improve bronchial hyperresponsiveness in subjects with mild asthma.

PMID- 8520794
TI  - Relationship of skin test reactivity to decrements in pulmonary function in
      children with asthma or frequent wheezing.
AB  - We examined the relationship between skin test reactivity and level of FEV1 in a
      stratified random sample of U.S. children 6 to 12 yr of age with asthma or
      frequent wheezing, studied as part of the Second National Health and Nutrition
      Survey (NHANES II). Subjects were considered symptomatic if they reported asthma
      or wheezing. Spirometry was performed according to ATS standards. Skin test
      reactivity to Alternaria, Bermuda grass, cat, dog, house dust, mixed long and
      short ragweed, oak, and rye grass allergens was determined. House dust mite (-17%
      FEV1; 95% CI, -9 to -25), dog (-28% FEV1; 95% CI, -11 to -42), and oak (-26%
      FEV1, 95% CI, -16 to -35) were associated with the greatest decrements in FEV1.
      In general, indoor allergens (-13% FEV1; 95% CI, -6 to -20) were associated with
      greater effects than outdoor allergens (-5% FEV1; 95% CI, -2 to -13). The
      association of indoor allergens with reduced FEV1 was greater in girls (-16%
      FEV1; 95% CI, -5 to -25) than in boys (-8% FEV1; 95% CI, -3 to -13).
      Sensitization to indoor allergens among symptomatic children 6 to 12 yr of age
      was associated with decrements in level of FEV1.

PMID- 8520796
TI  - American Thoracic Society. Single-breath carbon monoxide diffusing capacity
      (transfer factor). Recommendations for a standard technique--1995 update.

PMID- 8520795
TI  - Oxygen cost of breathing in patients with emphysema or chronic bronchitis in
      acute respiratory failure.
AB  - This study compared the oxygen cost of breathing (VO2 resp) in 19 patients with
      severe chronic obstructive pulmonary disease intubated for acute respiratory
      failure. Ten patients showed radiologic (X-ray and/or computed tomographic scan)
      evidence of emphysema. The remaining ones were considered as having chronic
      bronchitis. Measurements were made just before extubation. Despite similar
      expiratory airflow obstruction, patients with emphysema exhibited significantly
      higher VO2 resp than patients with chronic bronchitis (109 +/- 61 versus 42 +/-
      26 ml/min/m2, respectively; p < 0.006). Moreover, emphysema was associated with
      nutritional depletion assessed through decreases in body mass index (emphysema:
      17.9 +/- 3.5 kg/m2; chronic bronchitis: 28.8 +/- 8.2 kg/m2; p < 0.005). This
      seemed to affect somatic stores (significant decreases in arm muscular
      circumference and triceps skin-fold thickness, whereas visceral stores were
      preserved (no decreases in serum albumin, serum prealbumin, and retinol binding
      protein). Malnutrition appeared to be the consequence of a hypermetabolic state
      of the respiratory muscles, with a significant negative correlation between VO2
      resp and body mass index, arm muscular circumference, and triceps skinfold
      thickness (p < 0.05). Total oxygen consumption normalized for body surface was
      similar in the two groups. Thus, in emphysematous patients, the oxygen available
      for tissues other than respiratory muscles was significantly reduced (emphysema:
      124 +/- 51 ml/min/m2; chronic bronchitis: 207 +/- 78 ml/min/m2; p < 0.02). This
      could explain nutritional differences observed between patients with emphysema
      and those with chronic bronchitis.

PMID- 8520797
TI  - American Thoracic Society. Role of the pulmonary and critical care medicine
      physician in the American health care system.

PMID- 8520798
TI  - Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy
      in patients with Wegener's granulomatosis.

PMID- 8520799
TI  - [Experimental models of toxoplasmosis. Pharmacological applications].
AB  - Toxoplasma gondii is an ubiquitous protozoan parasite causing severe or life
      threatening infections in immunocompromised patients and in congenitally infected
      infants. Animal models have been extensively used to describe the pathology of
      infection and to identify new effective drugs for the treatment of congenital
      infections, chrorioretinitis and toxoplasmic encephalitis. Although inherent
      differences between man and animal can reduce the relevance of data obtained
      experimentally, animal models have greatly improved our knowledge on the various
      aspects of toxoplasmosis. Toxoplasma infection can be easily obtained in most
      laboratory animals, with exception of rats which are partially resistant.
      According to the strain used, the resulting infection may be acute, subacute or
      chronic, and can be monitored either by the survival of animals, the
      histopathological examination of lesions or, preferably, by titration of
      parasites in infected tissues using subinoculation to mice or tissue culture.
      This latter method has proved particularly useful to describe the kinetics of
      infection in host tissues and to assess the efficacy of drugs, according to their
      pharmacokinetics and tissue distribution. The relevance of results obtained in
      animal models of congenital toxoplasmosis and of chrorioretinitis is more
      questionable, due to the marked differences between the mode of infection in
      humans and in animals. Experiments performed in primates provided valuable
      informations for the management of therapy of congenital toxoplasmosis but were
      of limited interest for ocular toxoplasmosis. The pathogeny of toxoplasmic
      encephalitis is still poorly understood, and no experimental model is fully
      satisfactory to produce focal encephalitic lesions as observed in
      immunocompromised humans. Acute infections with highly virulent strains induce
      disseminated infection with major pulmonary and brain involvement, and thus can
      be used to assess the efficacity of drugs in these tissues. Direct inoculation of
      tachyzoites into brain tissue can induce focal encephalitis but this model is of
      difficult use for large scale studies. Although cellular immunity is mainly
      responsible for the control of toxoplasmosis at the chronic stage, administration
      of immunosuppressive drugs does not usually result in focal brain reactivation;
      such reactivation can only be obtained using antibodies against CD8 and CD4 T
      lymphocytes or interferon gamma. Another experimental approach is the use of
      genetically immunodeficient animals: these models are of limited interest for
      pharmacological research since infection of nude or T depleted mice usually
      results in a dissemination of infection; however, using these models it could be
      clearly demonstrated that immunity plays a major adjunctive role in the control
      of acute infection. Concurrent infections between viruses and parasites is a
      common feature in immunocompromised patients and especially during AIDS.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8520800
TI  - Babesia divergens: an ELISA with soluble parasite antigen for monitoring the
      epidemiology of bovine babesiosis.
AB  - An enzyme linked immunosorbent assay (ELISA) for bovine babesiosis caused by
      Babesia divergens was developed to analyse the evolution of the serological
      status of cattle living in an enzootic area. The antigen used was a soluble
      extract of B. divergens obtained from in vitro culture. Specificity, evaluated
      with negative sera, was 96.6%. The ELISA was compared to indirect
      immunofluorescence analysis (IFA) on naturally or experimentally infected
      animals. It appeared that IFA was positive for at least seven or eight weeks; on
      the contrary, B. divergens-specific antibodies were only transitorily detected by
      ELISA. Furthermore, the ELISA was more sensitive than the IFA for the detection
      of post-infection antibody increases, particularly when infection-pressure was
      low. These results suggest that IFA and ELISA could be complementary tools in
      epidemiological surveys; indeed, this ELISA could be the most efficient tool to
      detect new infections in cohort monitoring.

PMID- 8520801
TI  - Non specific resistance against malaria pre-erythrocytic stages: involvement of
      acute phase proteins.
AB  - Levels of different acute phase proteins were compared in sera from parasitaemic
      and non-parasitaemic women living in a Plasmodium falciparum endemic area of
      Thailand. The ability of their sera to interfere with hepatic stage development
      of the parasite was examined. Correlations were found between levels of alpha-1
      antitrypsin, alpha-2 macroglobulin, hemopexin and the potential of sera to block
      hepatocyte invasion by the sporozoite.

PMID- 8520802
TI  - Evaluation of Dirofilaria immitis excretory/secretory products for
      seroepidemiological studies on human dirofilariosis.
AB  - The usefulness of excretory/secretory (E/S) products of adult Dirofilaria immitis
      for the diagnosis of human dirofilariosis was evaluated in 97 human sera using an
      ELISA and a Western Blot analysis with E/S antigens. Results of the ELISA
      analysis show that in healthy individuals from an endemic area seropositivity is
      high (22%). Immuno Blot analysis shows that the reaction pattern with E/S
      antigens differentiates healthy seropositives, which recognize a 43 kDa band,
      from patients with pulmonary dirofilariosis, which specifically recognize bands
      between 22-28 kDa.

PMID- 8520803
TI  - Filariae from a wild gorilla in Gabon with description of a new species of
      Mansonella.
AB  - A search for filariae was performed on a wild male Gorilla g. gorilla from the
      Lope Reserve in Gabon, which had died as a result of injuries inflicted by
      another male gorilla. A female worm of Loa loa and female worms of two species of
      Mansonella were recovered from the deep tissues of a wounded thigh. In order to
      analyze these Mansonella, specimens of M. (E.) perstans, M. (E.) vanhoofi and M.
      (E.) streptocerca from the Collections of the Museum National d'Histoire
      Naturelle de Paris have been studied and new important discriminative characters
      characterised, such as the body-swellings in M. (E.) perstans, due to the
      presence of coelomocytes as in South-american M. (Tetrapetalonema) spp. One of
      the Mansonella from this gorilla was not identified, but the body-swellings and
      the microfilarial morphology suggested a possible similarity with M.
      (Esslingeria) perstans. The other species is new; M. (E.) lopeensis n. sp. is
      distinguished by its large size, lack of body-swellings, structure of the
      tegumental sheath, complex vagina, and a tail with a subterminal constriction, a
      terminal bend and large lappets. Histological sections of organs of this gorilla
      also showed a microfilaria of M. (E) leopoldi in the blood vessels of the liver,
      and a male of Mansonella sp., interestingly situated in an afferent lymphatic
      vessel of an axillary lymph node.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520804
TI  - Lack of interaction between pantoprazole and digoxin at therapeutic doses in man.
AB  - Substituted benzimidazole inhibitors of the gastric H+/K+ATPase may interact with
      the cytochrome P450 enzyme system and alter the pharmacokinetics of
      coadministered drugs. On the other hand, changes in intragastric pH might alter
      the absorption of other drugs. The primary aim of the present study was to
      determine whether pantoprazole modifies the steady-state serum concentrations of
      orally administered digoxin. Secondary aims were the influence of digoxin on the
      pharmacokinetics of pantoprazole as well as safety and tolerability. Eighteen
      healthy volunteers received a single oral dose of pantoprazole (40 mg) and serum
      concentrations were determined. Three to 10 days later, subjects received in a
      single-blind, randomized, crossover fashion oral beta-acetyldigoxin (0.2 mg)
      twice daily and concomitant oral pantoprazole (40 mg) or placebo once daily for 5
      days. Serum concentrations of pantoprazole and digoxin were determined on day 5.
      Primary characteristics for confirmative assessment of no interaction were AUC
      and Cmax of digoxin. Lack of interaction in the sense of equivalence was
      concluded for both digoxin (with and without pantoprazole) and pantoprazole (with
      and without digoxin) as the 90%-confidence intervals of the respective AUC- and
      Cmax-ratios were within the equivalence range of 0.8-1.25. Pantoprazole did not
      influence the characteristic ECG modifications (T-wave) caused by digoxin. Both
      drugs were well tolerated and no adverse events or clinically relevant
      alterations in vital signs or clinical laboratory parameters were observed during
      treatment. In conclusion, pantoprazole and digoxin may be administered
      concomitantly without the need for dose adjustment.

PMID- 8520805
TI  - Reasons for prescribing cognition enhancers in primary care. Results of a
      representative survey in Lower Saxony, Germany.
AB  - With regard either to the controversial debate about the efficacy of cognition
      enhancers (CEs) or to the high costs which the frequent prescription of these
      drugs causes the German health system's economy, we wanted to know what
      physicians expect from a therapy with these drugs. We performed a representative
      survey (response rate 83.2%) in Lower Saxony, Germany from February to July 1993.
      We designed two written case vignettes which described either a patient with
      slight memory problems or a moderately demented patient who also suffers from
      common systemic disorders. In a face-to-face interview 145 general practitioners
      and primary care internists (family physicians) and 14 community
      neuropsychiatrists answered the question, whether they would prescribe CEs to
      each of the patients described and what they would expect from this therapy.
      70.4% of all physicians would prescribe a cognition enhancer to the slightly
      impaired patient and 63.5% to the multimorbid moderately demented patient,
      respectively. More than 50% of the family physicians would not expect any
      positive therapeutic effect in both patients, while the neuropsychiatrists did so
      in 57.1% in the patient with slight memory disturbances and in 35.7% in the
      moderately demented patient. A positive effect on cognition was expected by 28.2%
      of all physicians in the slight and by 18.3% in the moderately impaired patient,
      respectively. Other reasons mentioned were amelioration of cerebral perfusion and
      drive, as well as effects on disease progression. In conclusion, the results of
      this study clearly demonstrate that cognition enhancers are prescribed in spite
      of major doubts in their efficacy.

PMID- 8520806
TI  - Comparative efficacy of diclofenac dispersible 50 mg and ibuprofen 400 mg in
      patients with primary dysmenorrhea. A randomized, double-blind, within-patient,
      placebo-controlled study.
AB  - Sixty female out-patients suffering from moderate to severe primary dysmenorrhea,
      aged 14-40 years (mean 27 years), entered this randomized, double-blind, 3
      period, within-patient study, evaluating the efficacy and tolerability of
      diclofenac dispersible 46.5 mg (equivalent to 50 mg of diclofenac sodium),
      ibuprofen 400 mg and placebo taken up to 4 times daily for a maximum of 3 days.
      Pain relief was evaluated on a verbal rating scale (0 = none, 1 = slight, 2 =
      moderate, 3 = considerable, 4 = complete) at 0.5, 1,2,3,4,5 and 6 hours after the
      first dose; the weighted sum of pain relief scores over the 6-hour observation
      period was also investigated (TOTPAR-6). Pain intensity was assessed on a verbal
      rating scale (0 = nil, 1 = mild, 2 = moderate, 3 = severe) at baseline and at the
      above mentioned time points; the weighted sum of pain intensity differences at
      each time point was also analyzed (SPID-6). A rescue medication was permitted 1
      hour or more after the intake of the test drug: in such cases the last value of
      pain intensity/relief scores was carried forward and used for the analysis. A
      global evaluation of efficacy and of trial medication as compared to her usual
      medication was performed by the patient at the end of each treatment period.
      Finally, adverse experiences were recorded throughout the study period. Analysis
      of covariance and Koch's adaptation of the Wilcoxon-Mann-Whitney rank sum test
      were used, where appropriate, for statistical analysis. Mean TOTPAR-6 values for
      diclofenac dispersible, ibuprofen and placebo were 16.5, 17.8 and 14.7,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520807
TI  - Glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB): interindividual
      variability in human liver, lung, kidney and intestine.
AB  - The rate of glutathione conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) was
      measured in specimens of human liver (n = 93), sigmoid colon (n = 56), renal
      cortex (n = 67) and lung (n = 68). In the liver there was a weak but significant
      (r = - 0.247 p = 0.017) negative correlation between the activity of glutathione
      transferase and the liver donor's age. Such a correlation was not found in the
      renal cortex, lung and colon. In the renal cortex and in lung the rate of
      glutathione conjugation with CDNB was a little but significantly (p < 0.05)
      higher in women than men, whereas no sex-dependent difference was observed in the
      liver and colon. The distribution of glutathione transferase activity was
      polymorphic in the mucosa of colon and renal cortex of men but not in that of
      women. Smoking seems not to affect the glutathione conjugation rate with CDNB in
      lung. The activity of glutathione transferase was 2-, 6-, and 7-fold greater in
      liver than in the renal cortex, lung and colon, respectively. There was a large
      interindividual variability of the hepatic glutathione transferase activity, and
      because this variability, 15% of the population studied catalyzed the glutathione
      conjugation with CDNB at a rate similar to those of the renal cortex and
      duodenum. The subjects with low expression of the hepatic glutathione transferase
      should be more exposed to the effects of toxic and carcinogenic compounds.

PMID- 8520808
TI  - Dopaminergic influence on the cardiovascular response to exercise in normotensive
      and hypertensive subjects.
AB  - Fourteen subjects (normotensive, hypertensive) were studied at the Vargas
      Hospital of Caracas. They were treated with placebo (2 periods), domperidone, a
      peripheral dopaminergic blocker, at the daily oral dose of 40 mg, and
      metoclopramide, a central and peripheral dopaminergic blocker, at the daily oral
      dose of 40 mg. All placebo and active drug periods lasted 1 week. Cardiovascular
      hemodynamic parameters (blood pressure, heart rate) were measured before, during
      and after submitting subjects to treadmill exercise according to the Bruce's
      protocol. Metoclopramide decreased significantly heart rate before and during
      exercise stress and systolic blood pressure during stage 1 exercise in
      normotensive subjects. Domperidone decreased significantly heart rate before and
      during exercise stress, and systolic blood pressure during stage 3 exercise in
      hypertensive subjects. Neither heart rate nor blood pressure were changed
      significantly after 8 minutes resting period post exercise. Our results suggest
      the existence of an excitatory modulatory influence of dopaminergic influence
      during exercise over the sympathetic activity.

PMID- 8520809
TI  - Metoclopramide blocks bromocriptine induced antihypertensive effect in
      hypertensive patients.
AB  - Two groups of patients with essential hypertension were studied at the Vargas
      Hospital of Caracas. The first group of 9 patients under placebo treatment for 1
      week received a single 2.5 mg oral dose of bromocriptine. Cardiovascular and
      biochemical parameters including arterial pressure, heart rate, plasma renin
      activity, and plasma aldosterone levels were evaluated during the 6-hour period
      before and after the administration of drugs. The second experimental design was
      as follows: 9 patients received 30 mg metoclopramide daily (divided in 3 doses)
      for 1 week. At the end of the period a single oral dose of 2.5 mg of
      bromocriptine was given to each patient. The cardiovascular and biochemical
      parameters were also determined. Bromocriptine reduced both systolic and
      diastolic arterial pressure. The peak antihypertensive effect was shown 3 hours
      after administration of the drug, but the reduction of arterial pressure lasted
      approximately 6 hours. At the same time bromocriptine reduced plasma aldosterone
      levels and plasma renin activity. This reduction persisted 6 hours after its
      administration. Metoclopramide reversed the antihypertensive effect of
      bromocriptine and its effect on aldosterone secretion and plasma renin activity.
      We conclude from these findings that bromocriptine acts as an antihypertensive
      agent by stimulating DA2 dopaminergic receptor, the dopaminergic receptor
      involved in aldosterone and renin secretion is possibly DA2.

PMID- 8520810
TI  - Combined drug therapy with diltiazem, dextran, and hydrocortisone (DDH therapy)
      for late cerebral vasospasm after aneurysmal subarachnoid hemorrhage: assessment
      of efficacy and safety in an open clinical study.
AB  - Late cerebral vasospasm after subarachnoid hemorrhage (SAH) is a disastrous
      phenomenon for the patients and a definite treatment has not been established. We
      studied 48 consecutive patients receiving high-dose diltiazem (5
      micrograms/kg/min) injection combined with dextran and hydrocortisone to late
      cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). All but 2
      patients underwent surgery within 72 hours after SAH. Diltiazem was continuously
      given via a central venous line for up to 2 weeks in conjunction with simple
      cisternal drainage. 5% of dextran solution (500 ml/day) was infused for 7-10
      days. Hydrocortisone was given 1,600 mg on the first day, then the dose was
      gradually decreased over 14 days. Symptomatic vasospasm (SVS) occurred in 5
      patients (10.4%), 4 patients recovered, but 1 had severe neurological deficit. A
      low density area on CT-scan was observed in 2 patients. Thirty patients (62.5%)
      had good recovery, 10 patients (20.8%) had moderate disability, 3 (6.3%) had
      severe disability and 3 (6.3%) had vegetative survival. Two patients died of the
      initial brain damage. There were no severely hypotensive side effects. However, 3
      patients showed atrioventricular blockage on electrocardiogram. These side
      effects subsided after the dose of the drug was decreased or administration was
      stopped altogether. These findings show that high-dose calcium antagonist
      diltiazem therapy combined with dextran and hydrocortisone injection is safe and
      effective for prevention of late cerebral symptomatic vasospasm after SAH.

PMID- 8520811
TI  - 150 mg fluconazole does not substantially increase the effects of 10 mg midazolam
      or the plasma midazolam concentrations in healthy subjects.
AB  - Fluconazole, an azole antifungal agent, moderately inhibits the CYP3A-mediated
      metabolism of midazolam in vitro. We therefore studied whether such an
      interaction takes place in vivo following oral administration of these drugs,
      given as relevant double blinded doses in capsule form. In study I parallel
      groups of healthy subjects received oral midazolam 10 mg (MID 10) or 15 mg (MID
      15), placebo, or MID 10 mg + 150 mg fluconazole (FLU) given 2 h earlier.
      Objective and subjective performance tests were made before, and 30 and 90 min
      after the intake of midazolam. MID 10 and MID 15 moderately impaired performance
      on digit symbol substitution, letter cancellation and flicker fusion tests, and
      visual analogue scales revealed mild sedation. FLU + MID 10 had similar or
      slightly stronger effects than MID 10; it differed from MID 10 in that it lowered
      the flicker fusion threshold and produced subjective slowness and overall
      impairment. In study II 5 subjects received MID 10 after placebo, after FLU, and
      after 750 mg erythromycin (ERY) at 1-week intervals, following a crossover and
      double-blinded study design. Blood was sampled before MID intake and 30, 60 and
      90 min after it, and performance was measured. FLU and ERY increased the effect
      of MID on flicker fusion and letter cancellation performances, and increased the
      HPLC-assayed plasma midazolam (ERY + 100%, FLU + 50%) in comparison to that
      measured after MID ingested alone. When the concentrations of midazolam together
      with its active metabolite alpha-OH-midazolam were assayed by radioreceptor
      technique the increases caused by ERY and FLU were less and compatible with the
      pharmacodynamic data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520812
TI  - Relative bioavailability of controlled-release oral morphine sulfate during
      naltrexone blockade.
AB  - The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled
      release oral morphine sulfate in normal volunteers was determined using a
      randomized, 2-way crossover, analytically blinded study design. Although
      naltrexone did not qualitatively alter the concentration-time curve for
      controlled-release morphine, the area under the plasma morphine concentration
      time curve from 0-24 h (AUC0-24) was significantly greater (p < 0.01) for
      morphine given with naltrexone (265 ng x h/ml) than for morphine given alone (215
      ng x h/ml). Compared to morphine given alone, the apparent absorption half-life
      of morphine was decreased from 0.94-0.58 h (p = 0.01) and Cmax was increased from
      28.17 ng/ml to 32.26 ng/ml (p = 0.04) during naltrexone blockade, whereas the
      Tmax and apparent elimination half-life of morphine were not significantly
      affected. The minimal differences in morphine bioavailability indicate naltrexone
      may be useful in comparative bioavailability studies of high-dose opioids in
      opioid-naive normal volunteers.

PMID- 8520813
TI  - [Prevention of fatal asthma: how to identify the patient at risk?].

PMID- 8520815
TI  - [Smoking among maritime workers in the province of Guipuzcoa. An epidemiological
      study].
AB  - Smoking is the principal environmental cause of human disease and seafarers are
      often heavy smokers as a consequence of difficult working conditions. The object
      of this study was to determine the prevalence of smoking among seafarers and
      possible associated factors. Cross-sectional descriptive study. Interviewers
      administered questionnaires to 834 seafarers between 40 and 60 years of age who
      were registered members of the marine health and social services authority of
      Guipuzcoa, whether they were active (working) or passive (unemployed or retired).
      Expiratory concentrations of CO were also measured. Smokers accounted for 47.5%.
      Average consumption was 33.9 packs/year (p/y); CO in expired air was 26.1 ppm. Ex
      smokers accounted for 23.7% (28.2 p/y; 6.0 ppm). The percentage of smokers was
      higher among fishermen of the high seas than among coastal fishermen (59.5%
      versus 38.0%; p < 0.001); consumption of cigarettes of both smokers and ex
      smokers (35.9-27.2 p/y; p < 0.001) and mean CO concentration in expired air (18.8
      12.4 ppm; p < 0.001) were also found to be higher in this group. Those who had
      consumed more cigarettes over the course of a lifetime were active seafarers
      (41.1-30.5 p/y; p < 0.001), but among them were also more ex-smokers (30.8-22.2%;
      p = 0.04) and fewer current smokers (35.6-50.0%; p = 0.002). Fishing the high
      seas was the only variable associated with cigarette consumption; being
      unemployed or retired was the only factor associated with quitting.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520814
TI  - [Correlation between sensitivity of the cytogenetic and cytological analysis and
      thoracoscopic findings in the study of malignant pleural effusions].
AB  - We studied 104 patients with pleural effusion. All underwent thoracoscopic
      exploration to allow direct examination of any pleural lesions present. At the
      same time pleural biopsies for histopathologic study and samples of pleural fluid
      for cytopathologic and cytogenetic study were taken. The volume of fluid in
      pleural cavity was also measured. The aims of the study were: a) to evaluate the
      sensitivity of cytogenetic analysis and cytopathology, both separately and
      together, and b) to look for a correlation between the sensitivity of these cell
      studies and the following thoracoscopic findings: tissue biopsy of pleural
      neoplasms, volume of pleural effusion and extension of neoplastic lesions in the
      pleural cavity. Seventeen of the pleural liquids studied were benign and 87 were
      neoplastic. Cytopathology was sensitive in 55% of the neoplastic cases and
      cytogenetic study was sensitive in 49%. Sensitivity rose to 74% when both
      techniques were applied. Cytogenetic study yielded a higher percentage of correct
      diagnoses in the group with hematologic neoplasia, whereas cytopathology was
      correct more often in cases of solid tumors, though these differences were not
      statistically significant. Use of both techniques resulted in correct diagnosis
      in 92% of patients with mesotheliomas. The number or correct diagnoses achieved
      with cytopathology tended to increase with size of macroscopic pleural lesion
      whereas cytogenetic study was more sensitive in patients with minimal or
      incipient pleural involvement. There were no statistically significant
      differences in sensitivity of cytopathology and cytogenetic analysis with regard
      to volume of pleural effusion.

PMID- 8520816
TI  - [Prediction of maximal ventilation during exercise in patients with chronic
      obstructive pulmonary disease].
AB  - To analyze the validity of baseline lung function parameters as predictors of
      maximal exercise ventilation (VEmax) in patients with chronic obstructive
      pulmonary disease (COPD), we studied 33 stable patients (FEV1 43.6 +/- 16.8%,
      FEV1/FVC% 48.4 +/- 9.2, FRC 156.8 +/- 32.7% and RV 212 +/- 53.9%). The sample was
      later divided into 3 groups based on severity of disease (severe, moderate or
      mild) in order to determine whether ability to predict VEmax increased with
      airways obstruction (FEV1 26.9 +/- 4.9%, 40.2 +/- 3.5% and 63.9 +/- 10%,
      respectively). The patients underwent lung function testing at rest and after a
      progressive stress test, with the maximal reading taken with the subject on a
      tread mill. We found greater correlation between VEmax and RV, FEV1 and FRC (r = 
      0.77, 0.75 and -0.74, respectively); the correlation was stronger in patients
      with severe COPD, in whom FEV1 was under 35% of the predicted value (r = -0.88,
      0.753 and -0.83, respectively). Correlation decreased or disappeared with less
      functional impairment. Prediction of VEmax was more reliable with equations that
      employed FEV1 accompanied by data reflecting degree of insufflation, RV or FRC
      (VEmax = 45.2 +/- 8.98 x FEV1 - 5.07 x RV; r2 = 0.72) than with equations based
      on FEV1 alone (VEmax = 14.79 + 15.03 x FEV1; r2 = 0.56). We therefore conclude
      that ventilatory limitation during exercise in patients with COPD is better
      defined by considering parameters related to lung insufflation along with those
      reflecting degree of expiratory obstruction, given that the former affect the
      greater or lesser efficacy of muscles under stress.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8520817
TI  - [Malignant pleural mesothelioma: clinical characteristics, prognostic factors and
      treatment].
AB  - Malignant pleural mesothelioma soon leads to death no matter what type of
      treatment is provided. We discuss the clinical signs, prognostic factors and
      treatment given in 41 cases managed over the past 13 years in our oncology
      department. 32% had been exposed to asbestos, 61% were 60 years old or younger,
      71% had a Karnofsky's index > or = 80% and 63% were stage I (Butchart). The first
      symptom leading to diagnosis was pain in 66% and mean time between first symptom
      and diagnosis was 3 months. Thirty patients never experienced full remission of
      disease: 15 were treated with palliative chemotherapy (CHT), 1 with palliative
      radiotherapy (RT), 5 with partial pleurectomy (PP) plus RT and/or CHT. Nine were
      given symptomatic treatment only. Only 11 (27%) patients experienced full
      remission after treatment: 7 had had extrapleural pneumonectomy, 2 had been given
      CHT and RT series and 4 had undergone PP with or without RT and/or CHT follow-up.
      Only 3 of these patients were still alive with no relapse more than 1 year later.
      Mean survival was 8 months. Univariate analysis revealed that the prognostic
      factors influencing survival were age and Karnofsky's index. Patients initially
      treated with surgery had a higher rate of survival. In conclusion, only
      Karnofsky's index and age were prognostic factors in our series. The better
      survival of patients initially treated surgically is probably related to prior
      screening.

PMID- 8520818
TI  - [Diagnosis of obstructive sleep apnea syndrome. Consensus report from the
      Respiratory Insufficiency and Sleep Disorders Group].

PMID- 8520819
TI  - [Availability of technical resources for diagnosis and treatment of sleep
      obstructive apnea syndrome in state hospitals in Spain].

PMID- 8520820
TI  - [Procedures of viral identification in respiratory infections].

PMID- 8520821
TI  - [Obliterating bronchiolitis with organized pneumonia. Experience in a general
      hospital].
AB  - Bronchiolitis obliterans with organizing pneumonia (BOOP) is a histopathologic
      entity that has been described in association with numerous clinical conditions.
      In the 1980s an idiopathic form was described as a definite clinicopathologic
      entity differentiated from other infiltrative pulmonary processes. We present 7
      patients diagnosed of BOOP over the past 6 years and discuss their clinical and
      radiologic signs as well as their response to steroid treatment. Our patients'
      evolution was subacute, cough and fever being the main symptoms. Lung function
      tests revealed a pattern that was predominantly restrictive. Radiology showed 1
      or several alveolar infiltrates in all patients; these were migratory in 3.
      Bilateral pleural effusion with marked eosinophilia in pleural fluid was observed
      in 1 patient. In another cavitated nodules were present in chest-X-ray, with no
      evidence of vasculitis in tissue examination. All patients were treated with
      steroids (mean 10 months) and a low maintenance dose was required in only 1. The
      remaining patients experienced full recovery.

PMID- 8520822
TI  - [Pulmonary granulomatosis caused by lentil aspiration].
AB  - Pulmonary nodular granulomatosis caused by aspirated lentils is a rare entity. We
      report the case of a healthy 8 years-old girl who suffered a choking life
      threatening choking event during a meal, with cardiorespiratory arrest. After a
      delay of one month delay without symptoms, she developed respiratory distress
      with radiologic changes. Lung biopsy disclosed foreing body granulomas. Steroids
      were not used because of their uncertain effectiveness in these cases. One year
      later the patient's progress was satisfactory.

PMID- 8520823
TI  - [Chylothorax and liver cirrhosis].

PMID- 8520824
TI  - [Pulmonary edema and mediastinal emphysema caused by strangulation].

PMID- 8520825
TI  - [Repeated microtraumas and venous thromboembolic disease].

PMID- 8520826
TI  - [Hypercalcemia and bronchogenic carcinoma].

PMID- 8520827
TI  - Light at the end of the tunnel.

PMID- 8520828
TI  - Professional standards in cell and tissue processing.
AB  - In the United States, standards for cell and tissue processing have been
      developed by a variety of professional tissue banking organizations. Several
      organizations, including the American Association of Tissue Banks and the Eye
      Bank Association of America, have accreditation programs for member institutions.
      Some governmental agencies, such as the New York State Department of Health and
      the Food and Drug Administration, have adopted strict regulations, which may
      subject noncompliant tissue banks to certain enforcement actions. Professional
      tissue banking organizations have also issued guidelines that provide
      recommendations for implementing efficacious policies and procedures for the
      acquisition, processing, storage, and distribution of tissues.

PMID- 8520829
TI  - Application of quality assurance practices in processing cells and tissues for
      transplantation.
AB  - Attention to issues of quality assurance from the early stages of development of
      experimental cell therapies provides a margin of safety for recipients. Adherence
      to minimum standards of practice at acquisition, processing, storage, and
      implantation ensures not only this baseline safety factor for patients, but also
      provides a baseline for comparative evaluations between different studies or
      different banks. This paper describes the basic components of a quality assurance
      program tailored to laboratories and facilities that collect, process, or
      distribute human cells and tissues for transplantation. These components include
      policy and procedure manuals, donor screening practices, processing procedures
      evaluation and control, training and education programs, auditing and
      investigation roles, responsibility for release of grafts, and recordkeeping and
      traceability requirements. References and resources for detailed information
      related to good manufacturing practices and good clinical and laboratory
      practices are provided. Standards, regulations, and current legislation
      specifically related to human cells and tissues intended for transplantation are
      also discussed.

PMID- 8520830
TI  - Infectious disease transmission through cell, tissue, and organ transplantation:
      reducing the risk through donor selection.
AB  - The incidence of cell transplant-transmitted infection is unknown and can only be
      inferred from prospective studies--that have not yet been performed and reported.
      The possibility of donor-to-recipient disease transmission through cell
      transplant therapy can be considered by reviewing the risk associated with other
      transplanted tissues and organs. Viral, bacterial, and fungal infections have
      been transmitted via transplantation of organs, tissue allografts such as bone,
      skin, cornea, and heart valves, and cell such as islets, hematopoietic stem
      cells, and semen. Several types of protozoan and worm parasites have been
      transferred via organ transplants. Bone allografts have transmitted hepatitis,
      tuberculosis, and human immunodeficiency virus (HIV-1). Corneas have transmitted
      rabies, Creutzfeldt-Jakob disease (CJD), hepatitis B (HBV), cytomegalovirus
      (CMV), herpes simplex virus (HSV), bacteria, and fungi. Heart valves have been
      implicated in transmitting tuberculosis and hepatitis B. HIV-1 and CMV
      seroconversion has been reported in patients receiving skin from seropositive
      donors. CJD has been transmitted by dura and pericardium transplants. Over the
      past several years, improvements in donor screening criteria, such as excluding
      potential donors with infection and those with behaviors risky for HIV-1 and
      hepatitis infection, and introduction of new donor blood tests have greatly
      reduced the risk of HIV-1 and hepatitis and may have nearly eliminated the risk
      of tuberculosis and CJD. Prior to use, many tissues are exposed to antibiotics,
      disinfectants, and sterilants, which further reduce or remove the risk of
      transmitted disease. Because organs, cells, and some tissue grafts cannot be
      subjected to sterilization steps, the risk of infectious disease transmission
      remains and thorough donor screening and testing is especially important.

PMID- 8520831
TI  - Ethical and policy issues in human fetal tissue transplants.
AB  - A review of human fetal tissue policies over the past 40 years reveals an
      increasing awareness that the use of this tissue raises unique ethical and policy
      issues. Initially it was believed that the use of fetal tissue was no different
      from using any other abandoned surgical waste specimen. Then state laws were
      passed requiring fetal tissue to be treated with the same respect and protection
      as tissue obtained from cadaver donors generally. Most recently, a few state and
      federal policies suggest that the use of fetal tissue requires a unique set of
      provisions, that it is unlike either the use of tissue from a routine cadaver
      donor or the use of tissue from abandoned waste specimens. In this paper we
      identify four central features of fetal tissue donation that make it a unique
      type of tissue donation requiring its own framework of respect and protection for
      the parties involved. We then critically review the most important current state
      and federal fetal tissue policies, including the NIH Revitalization Act of 1993.

PMID- 8520832
TI  - Homing and immunogenicity of murine stromal cells transfected with xenogeneic MHC
      class II genes.
AB  - Syngeneic (murine) and xenogeneic (canine) marrow-derived stromal cells were
      injected intravenously into SCID and normal mice to examine the homing pattern
      and persistence of these cells in vivo. By in situ hybridization, these stromal
      cells were detectable in the bone marrow cavity and the spleen 21 days after
      injection. Xenogeneic cells did not persist in normal mice but persisted in SCID
      mice. Conditioning of the recipients with irradiation or 5-fluorouracil (5-FU)
      treatment did not alter these results. In addition, syngeneic murine stromal
      cells were transfected with the genes for canine MHC class II (DRA + DRB) and
      transplanted into murine recipients to investigate their homing pattern and
      immunogenicity. These transfected syngeneic stromal cells did also home to marrow
      and spleen even in normal recipients. However, these cells led to sensitization
      of the host towards canine antigens as shown by accelerated skin graft rejection
      and delayed type hypersensitivity (DTH). Thus, immunodeficient (SCID) mice allow
      for the homing of xenogeneic stromal cells to hemopoietic organs and for
      prolonged persistence. In immunocompetent (normal) mice, no xenogeneic stromal
      cells were identified in spleen and marrow, either because of their inability to
      home or more likely because of immunological rejection. In contrast, syngeneic
      stromal cells expressing xenogeneic MHC class II genes did home to spleen and
      marrow and persisted even though the recipient had become sensitized. Their
      survival may be due to a loss of expression of the transfected gene.
      Alternatively, the presentation of these xenogeneic gene products in the
      hemopoietic organs was such that a cytotoxic response was not induced.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8520833
TI  - CD34 stem/progenitor cells purified from cryopreserved normal cord blood can be
      transduced with high efficiency by a retroviral vector and expanded ex vivo with
      stable integration and expression of Fanconi anemia complementation C gene.
AB  - A future possibility for treatment of genetic diseases may be gene therapy using
      autologous cord blood (CB) stem/progenitor cells. This might require
      cryopreservation of CB stem/progenitor cells prior to purification, gene
      transduction, and ex vivo expansion of cells. To address this possibility,
      nonadherent low density T-lymphocyte depleted (NALT-) cells from fresh or
      cryopreserved cord blood were sorted for CD34 phenotype, transduced with a
      recombinant retroviral vector encoding Fanconi anemia complementation C (FACC)
      gene, and cells expanded ex vivo in suspension culture for 7 days with growth
      factors. The results demonstrate: 1) high recovery of viable cells after thawing;
      2) high efficiency purification of CD34 cells from NALT- cells prior to and after
      cryopreservation; 3) high degree of expansion of nucleated cells and immature
      progenitors from CD34 cells before and after cryopreservation; 4) efficient
      transduction with stable integration and expression of newly introduced genes in
      cryopreserved and then sorted stem/progenitor cells, as detected prior to and
      after ex vivo expansion; and 5) high efficiency transduction of single isolated
      CD34 cells obtained from cryopreserved NALT- CB. This information should be of
      value for future studies evaluating the use of cryopreserved cord blood for gene
      transfer/gene therapy.

PMID- 8520834
TI  - Morphometric study of fetal brain transplants in the insular cortex and NGF
      effects on neuronal and glial development.
AB  - Homotopic grafts supplemented with nerve growth factor (NGF) speed the recovery
      from learning deficits observed following electrolytic lesions of the insular
      cortex in rats. NGF also reduces the time in which the activity of choline
      acetyltransferase (ChAT) is first detected inside the graft by histochemical
      techniques. It is not known whether this behavioral and biochemical recovery
      correlates with an advanced maturation of the cellular elements within the graft,
      presumably induced by NGF. To investigate the degree of maturation of neurons,
      glial cells and blood vessels in NGF-supplemented grafts, adult rats were
      lesioned electrolytically in the insular cortex, and homotopic embryonic grafts
      (E16) with or without NGF supplementation were transplanted into the lesion.
      Fifteen days post grafting, the rats were perfused and the brains stained using
      silver impregnation techniques. Our results showed that neuronal maturation, as
      evaluated through several morphometric parameters, was advanced in NGF
      supplemented grafts when compared with other experimental groups. Furthermore,
      grafts supplemented with NGF also showed significant increases in the number of
      neurons, oligodendrocytes, astrocytes and blood vessels. These observations
      indicated that the addition of NGF to insular cortex grafts promoted the
      maturation of neuronal and glial elements within the graft. They also support the
      possibility that the advanced morphological maturation of insular cortex grafts
      supplemented with NGF underlies the accelerated functional and biochemical
      recovery of animals with lesions of the insular cortex.

PMID- 8520835
TI  - Extensive axonal and glial fiber growth from fetal porcine cortical xenografts in
      the adult rat cortex.
AB  - Axonal growth from cortically placed fetal neural transplants to subcortical
      targets in adult hosts has been difficult to demonstrate and is assumed to be
      minimal; however, experiments using xenogeneic neural grafts of either human or
      porcine fetal tissues into the adult rat striatum, mesencephalon, and spinal cord
      have demonstrated the capability for long-distance axonal growth. This study
      reports similar results for porcine cortical xenografts placed in the adult rat
      cerebral cortex and compares these findings with results from cortical
      allografts. Adult rats that previously received unilateral cortical lesions by an
      oblique intracortical stereotaxic injection of quinolinic acid, were implanted
      with suspensions of either E14 rat or E38 xenogeneic porcine fetal cortical
      cells. Xenografted rats were immunosuppressed by cyclosporin A. The corpus
      callosum was intact in all cases and grafts were confined to the overlying
      cortex. After a 31-34 wk posttransplant survival period, acetylcholinesterase
      (AChE) staining and tyrosine hydroxylase (TH) immunocytochemistry revealed that
      both allo- and xenografts received host afferents. Retrograde tracer injections
      into the ipsilateral striatum and cerebral peduncle in allografted animals failed
      to show any axonal growth to either subcortical target. Using a porcine-specific
      axonal marker in xenografted animals, we found graft axons in white matter tracts
      (corpus callosum, internal capsule, cingulum bundle, and medial forebrain bundle)
      and within the caudate-putamen and both the ipsilateral and contralateral
      cerebral cortex. Graft axons were not found in the thalamus, midbrain, or spinal
      cord. In addition, using an antibody to porcine glial fibers, we observed more
      extensive graft glial fiber growth into the same host fiber tracts, as far
      caudally as the cerebral peduncle, but not into gray matter targets outside the
      cortex. These results demonstrate that porcine cortical xenograft axons and glia
      can extend from lesioned cerebral cortex to cortical and subcortical targets in
      the adult rat brain. These findings are relevant for prospects of repairing
      cortical damage and obtaining functional recovery.

PMID- 8520836
TI  - Migration of macrophage-like cells within encapsulated islets of Langerhans
      maintained in tissue culture.
AB  - Islets of Langerhans isolated from the pancreas and encapsulated in alginate
      polylysine-alginate micro-spheres can potentially serve as a self-regulating
      supply of insulin in response to glucose loads. A longitudinal ultrastructural
      and immunohistochemical study of encapsulated rat islets cultured in CMRL-1969
      media at a constant glucose concentration of 5.5 mmol/L (100 mg%) allowed several
      observations. First, acinar cells, which remain attached to isolated islets,
      disappeared within 1 wk in tissue culture. Damaged endocrine cells also
      disappeared at this time. Phagocytic cells having ultrastructural features
      suggesting that they are macrophages emerged from the islets within about a week
      and ingested portions of the inner layer of capsule polymer. These macrophage
      like cells retained these polymers until their death which occurred at around 1-2
      mo after isolation; at no time did we observe phagocytic cells actually breaching
      the microsphere capsules. Beta cells remained well-granulated over 90 days of
      culture but accumulated lipofuscin-like residual bodies. Under these conditions,
      these bodies began to accumulate appreciably after about one week in culture.

PMID- 8520837
TI  - Analysis of the serological and cellular sensitization induced by encapsulated
      human islets transplantation in type I and type II diabetes patients.

PMID- 8520838
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 8520839
TI  - Bimonthly update in lipidology: Nutrition.

PMID- 8520840
TI  - Bimonthly update in lipidology: Genetics and molecular biology.

PMID- 8520841
TI  - Bimonthly update in lipidology: Lipid metabolism.

PMID- 8520842
TI  - Bimonthly update in lipidology: hyperdipidaemia and cardiovascular disease.

PMID- 8520843
TI  - Bimonthly update in lipidology. Atherosclerosis: cell biology and lipoproteins.

PMID- 8520844
TI  - Bimonthly update in lipidology: Therapy and clinical trials.

PMID- 8520845
TI  - Profiling a landmark clinical trial: Scandinavian Simvastatin Survival Study.

PMID- 8520846
TI  - Statin therapy in clinical practice: new developments.

PMID- 8520847
TI  - The stimulation of the cholesterol esterification pathway by atherogenic
      lipoproteins in macrophages.
AB  - Cholesteryl-ester-loaded macrophages, or foam cells, are prominent features of
      atherosclerotic lesions and undoubtedly play important roles in lesion
      development. Foam cell formation involves the uptake of atherogenic lipoproteins
      or other cholesterol-rich particles by pathways that are down-regulated
      incompletely or not at all by cholesterol. In addition, postreceptor events that
      affect intracellular cholesterol metabolism play a critical role in foam cell
      formation. Increasing evidence shows that the ability of lipoproteins to
      stimulate cholesterol esterification is dependent upon a regulated and complex
      pathway that most likely involves one or more proteins in addition to the
      cholesterol esterifying enzyme itself. The molecular characterization of these
      proteins, as well as the study of intracellular cholesterol metabolism in vivo,
      represent important goals for our further understanding of foam cell biology and
      atherogenesis.

PMID- 8520848
TI  - Smooth muscle cells and atherosclerosis.
AB  - The role of smooth muscle cells in atherogenesis involves cell proliferation and
      accretion of cholesteryl ester. Smooth muscle cell proliferation, controlled by
      growth factors produced locally, contributes to progression of atheroma and to
      restenosis after percutaneous transluminal coronary angioplasty. Accretion of
      cholesteryl ester in smooth muscle cells is mediated by factors secreted by
      macrophages. Induction of the scavenger receptor in smooth muscle cells may
      promote the transformation to foam cells. Novel approaches to combat restenosis
      include gene transfer into smooth muscle cells using different vectors.

PMID- 8520849
TI  - Synthesis and secretion of apolipoprotein B from cultured liver cells.
AB  - Regulation of the assembly and secretion of apolipoprotein B-containing
      lipoproteins from liver cells is an extremely complex problem that is under
      investigation in numerous laboratories. During the past year, advances have been
      made in several relevant areas, including studies of the topography of
      apolipoprotein B as it translocates across the endoplasmic reticulum membrane,
      the regulation of translocation, the role of chaperons in this process, and the
      mechanisms governing the addition of core lipid to the nascent apolipoprotein B
      containing particle.

PMID- 8520850
TI  - Apolipoprotein A-I-containing lipoproteins and atherosclerosis.
AB  - Apolipoprotein A-I-containing lipoproteins represent a heterogeneous group of
      lipoparticles. Recent studies suggest that a specific subpopulation within the
      lipoprotein (AI) subclass may be more effective than other lipoproteins in
      promoting cholesterol efflux from cells and in the different steps of reverse
      cholesterol transport. This review describes the different apolipoprotein A-I
      containing HDL subfractions, their role in reverse cholesterol transport, and
      their metabolic interconversions and relationship with lipoprotein-modifying
      enzymes.

PMID- 8520851
TI  - Postprandial state and atherosclerosis.
AB  - Accumulating evidence suggests that triglyceride-rich lipoproteins are an
      independent risk factor for atherosclerosis. This epidemiological evidence first
      emerged as a result of studying postprandial lipaemia that characterized the
      metabolic capacity of triglycerides in the postabsorptive state, that is, under
      challenge. Studies of postprandial lipaemia were helpful to explain several
      effects of triglyceride-rich lipoproteins on cholesteryl-ester-rich lipoproteins.
      From these studies it became apparent that peculiarities of cholesteryl-ester
      rich lipoproteins, such as small LDL and small HDL, which have been associated
      with risk for atherosclerosis, were caused by impaired triglyceride metabolism.

PMID- 8520852
TI  - Triglyceride lipases and atherosclerosis.
AB  - Lipoprotein lipase is at the center of lipoprotein metabolism, unloading
      triglycerides for metabolic use in extrahepatic tissues, regulated in concert
      with energy metabolism by insulin and other factors, and converting the input of
      large triglyceride-rich lipoproteins to smaller, potentially atherogenic remnants
      that are either remodeled into LDL and HDL, or quickly cleared. In addition,
      lipoprotein lipase has turned out to be a multifunctional protein that also acts
      as a ligand for binding of lipoproteins to proteoglycans and receptors. Hepatic
      lipase has evolved more recently, and its main role appears to be in the
      remodeling processes.

PMID- 8520853
TI  - Cholesteryl ester transfer proteins, reverse cholesterol transport, and
      atherosclerosis.
AB  - Plasma cholesteryl ester transfer protein plays a central role in lipoprotein
      metabolism by exchanging cholesteryl esters with triglycerides. Human genetic
      deficiency is associated with increased HDL-cholesterol levels, whereas
      cholesteryl ester transfer protein overexpression in transgenic mice results in
      decreased HDL-cholesterol. Thus, it has been proposed that cholesteryl ester
      transfer protein deficiency is an antiatherogenic state. However, recent
      observations in human cholesteryl ester transfer protein deficiency and
      cholesteryl ester transfer protein transgenic mice also suggest antiatherogenic
      effects of the expression of this protein, probably reflecting its role in
      reverse cholesterol transport.

PMID- 8520854
TI  - Chylomicron remnants: hepatic receptors and metabolism.
AB  - Recent studies support a sequential model for hepatic processing and catabolism
      of chylomicron remnants. Removal of chylomicron remnants by the liver involves
      interaction with several macromolecules on the cell surface, including the LDL
      receptor and heparan-sulfate-bound hepatic lipase and apolipoprotein E.
      Endocytosis of chylomicron remnants into hepatocytes is mediated by
      apolipoprotein E and normally occurs through the LDL receptor. Interaction of
      chylomicron remnants with the LDL receptor-related protein, or another endocytic
      receptor with similar properties, occurs slowly, requiring modification of
      surface-bound chylomicron remnants, and serves as a backup mechanism that is
      utilized primarily when LDL receptors are deficient or down-regulated.

PMID- 8520855
TI  - Structure of cholesterol-containing particles accumulating in atherosclerotic
      lesions and the mechanisms of their derivation.
AB  - Structural and chemical modifications of plasma lipoproteins retained in
      atherosclerotic lesions, especially LDL, are a characteristic of atherogenesis.
      The major cholesterol-containing structures believed to be derived primarily from
      LDL are monomeric or aggregated native or modified LDL particles, cholesteryl
      ester droplets, liposomes rich in unesterified cholesterol, and ceroid
      lipofuscin. They are suggested to be formed primarily from LDL by combinations of
      oxidation, hydrolysis by proteases and esterases, fusion of neutral lipid
      components, and covalent interactions between lipid and protein components of
      oxidized LDL in lysosomes. Although many of these structures appear to be
      refractory to removal by reverse cholesterol transport mechanisms, they may
      possess functional properties that still need to be elucidated.

PMID- 8520856
TI  - The extracellular matrix and atherosclerosis.
AB  - The vascular extracellular matrix is a collection of vastly different
      macromolecules organized by entanglement and cross-linking into a biomechanically
      active polymer that imparts regional tensile strength, viscoelasticity, and
      compressibility to the atherosclerotic lesion. Each component of the
      extracellular matrix possesses unique structural properties that determine its
      separate roles during atherogenesis. Not only does this matrix provide the
      architectural framework that influences the structural integrity of the lesion,
      but it also provides the milieu for vascular cells and participates in the
      adhesive, proliferative, and migratory events that characterize lesion
      development. The fact that different components of the extracellular matrix
      selectively bind plasma proteins, growth factors, cytokines, and enzymes
      implicate these molecules in the regulation of key metabolic events in the
      formation of the atherosclerotic plaque. The extracellular matrix can no longer
      be thought of as simply an inert structural mass, but rather as a collection of
      molecules that possesses the capacity to 'instruct' and 'transduce the
      information' that 'drives' events central to the atherogenic process. A more
      thorough understanding of the nature and properties of the vascular extracellular
      matrix and the factors that regulate its accumulation would seem to be a
      reasonable goal if progress is to be made towards alleviating this disease.

PMID- 8520858
TI  - Proceedings of the Society for Quality Assurance annual meeting. New Orleans,
      Louisiana, October 3-6, 1994.

PMID- 8520859
TI  - Perspectives on the U.S. FDA Bioresearch Monitoring Program.
AB  - An overview is presented of the U.S. FDA Bioresearch Monitoring Program from the
      field perspective. The presentation includes current insight as to how FDA
      conducts field audits in various program areas and observations regarding shared
      responsibilities for ensuring both quality data and patient safety during the
      preclinical and clinical investigation processes.

PMID- 8520857
TI  - Use of somatic gene transfer to study lipoprotein metabolism in experimental
      animals in vivo.
AB  - Genetic manipulations of experimental animals have provided valuable information
      on lipoprotein metabolism in vivo. Somatic gene transfer is a novel method for
      introducing foreign genes into animals in vivo. Adenovirus-mediated transfer of
      genes for the LDL receptor, the receptor-associated protein, apolipoprotein A-I,
      apolipoprotein E, cholesterol 7 alpha-hydroxylase, and apolipoprotein B messenger
      RNA editing protein has resulted in high-level expression of these transgenes in
      mice and hamsters, and the production of interesting animal models of lipoprotein
      metabolism. Somatic gene transfer is a valuable tool for analyzing the role of
      transgenes in lipoprotein metabolism in vivo and for exploring the potential use
      of specific transgenes for human gene therapy.

PMID- 8520860
TI  - Those who do not remember the past....
AB  - A foundation stone for quality assurance is the ability to document past actions.
      The celebration of the 10th Annual Meeting of the Society of Quality Assurance
      allows all of us, who were somehow intimately involved in its beginnings, to
      reflect on the past actions of our industries and to contemplate what this
      history bodes for the future. The exciting expectations of global and regulatory
      agency harmonization beckon us into the 21st century. We eagerly rush to embrace
      the concepts of total quality management and to establish an international
      dimension for our Society. Just as the retrospective audit of the science we
      regulate is an integral part of our daily activities, however, so must the
      reflection on whence we came (and why) be an integral part of our planning for
      the future. There is a dark side to the history of why the Society persists to
      celebrate this 10th anniversary. What lessons of yesterday remain to help guide
      us all into tomorrow?

PMID- 8520861
TI  - U.S. EPA challenges and review--highlights of the Fiscal Year 1994 Inspection
      Program and EPA's laboratory accreditation considerations.
AB  - The reorganization and consolidation of the United States Environmental
      Protection Agency's (EPA's) Headquarters Enforcement and Compliance programs into
      a new Office of Enforcement and Compliance Assurance (OECA) is now complete. The
      Good Laboratory Practice (GLP) inspection program is now part of the Office of
      Compliance, one of the principal offices in this new organization. The role of
      the Office of Compliance and the implications of these changes for the Federal
      Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Toxic Substances Control
      Act (TSCA) GLP programs are addressed. Highlights of the fiscal year 1994
      inspection program are reviewed. The status of the Agency's consideration of
      laboratory accreditation is discussed.

PMID- 8520862
TI  - The 10 essential activities of the quality assurance unit.
AB  - It is certainly my pleasure to be here today. Several months ago, Pat Pomerleau
      invited me to be on your program. At the time, I had no idea that I would be
      speaking as Paul Lepore, private citizen, rather than Paul Lepore, regulator and
      bureaucrat. However, the Food and Drug Administration (FDA) made me an offer I
      could not refuse and, upon considerable thought, I retired effective September
      30, 1994. Immediately, I called Pat for advice on how to deal with my planned
      presentation before you. Graciously, she said that she did not believe that I
      would forget all I knew about Good Laboratory Practice (GLP) over 1 weekend and
      that the Society would love to have me anyway. Today, I intend to discuss the 10
      essential activities of a properly functioning quality assurance Unit (GAU). I
      will summarize the importance of records and documentation to the unit and I will
      close with some comments on achieving regulatory compliance. My remarks are
      intended to emphasize that an effective, active quality assurance unit is crucial
      for ensuring data quality, and that attention paid to day-to-day quality
      assurance activities will foster regulatory compliance.

PMID- 8520864
TI  - ISO 9000 laboratory accreditation. International Organization for
      Standardization.

PMID- 8520863
TI  - The use of total quality principles to achieve regulatory compliance in research
      laboratories.
AB  - Since the late 1980s, the U.S. Food and Drug Administration (FDA) has increased
      its focus on regulatory compliance. This is evidenced by an increase in warning
      letters, product seizures, injunctions, prosecutions, and recalls. This increased
      level of FDA enforcement activity is evidenced across all of the compliance
      regulations. Thus, the ability to comply with the Good Laboratory Practices
      (GLPs). Good Clinical Practices (GCPs) and Good Manufacturing Practices
      regulations could result in FDA enforcement activities and delays in the approval
      process for new products. Therefore, the ability to achieve compliance with the
      GLPs, GCPs, and GMPs in research laboratories is a key to business success in the
      1990s. Applying the principles of total quality is one way to address these
      important business issues. The principles of total quality (customer focus,
      improvement, involvement, leadership, and measurement) provide a methodology for
      ensuring success in a rapidly changing regulatory environment. The FDA needs to
      be treated as a customer by research organizations. Valid regulatory requirements
      need to be negotiated with the agency. Once these customer requirements have been
      identified, the quality unit needs to play a leadership role in translating these
      requirements into action plans. Quality units, no matter how skillful or good,
      cannot achieve success without involvement of the scientific staff and management
      group of their organizations. Without their involvement there will be no
      organizational commitment to compliance programs undertaken to meet the valid
      requirements of the FDA. Meeting these valid customer requirements will require
      improvement efforts. The many tools of quality improvement in achieving the
      desired improvements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8520865
TI  - Good clinical practices: past, present, and future.
AB  - Clinical quality assurance has its roots in the evolution of the GCPs.
      Historically, the fundamental elements of GCPs provided a springboard to develop
      and refine a paradigm of standard measurements to assure the integrity and
      quality of research. The research community spontaneously responded by
      voluntarily establishing quality assurance units and implementing auditing
      functions to ensure the highest standards in an industry that encompasses
      science, medicine, and ethics. Although clinical quality assurance is still
      unregulated in the United States, the performance of good clinical practices has
      become an integral part of the clinical research process and has impacted the
      research community on worldwide basis. The establishment of the EC guidelines,
      the WHO guidelines, and the International Conference on Harmonization are
      testaments to the increasing emphasis on the future of GCP-related activities.

PMID- 8520866
TI  - Pharmacoeconomics: an emerging discipline.
AB  - The economic pressures of cost containment, pricing competition, and managed care
      have bootstrapped the application of health economic evaluation into the
      specialized area of pharmacoeconomics. The rapid development of the field has
      lead to criticism within the discipline and skepticism from consumers of
      pharmacoeconomic studies. The need for consensus upon standards of design and
      analysis will result in guidelines and more stringent peer review. The relative
      merits of current approaches are reviewed with respect to the limitations and
      generalizability of each type of study and common pitfalls in the design,
      analysis, and promotion of pharmacoeconomic studies. Future trends and regulatory
      issues are discussed. Finally, the role of pharmacoeconomics in drug development
      and marketing is evaluated.

PMID- 8520867
TI  - Drug development history, "overview," and what are GCPs?
AB  - History shows that regulation of the pharmaceutical industry came about as a
      result of unfortunate incidences in which self-control by the industry was
      insufficient. All facets of drug manufacturing and preclinical laboratory
      research and development are regulated by GMPs and GLPs. Only part of the GCPs,
      as proposed, have become regulations. The pharmaceutical industry has an
      attrition rate of NCEs, from discovery to product, of 10,000 : 2. Research and
      development to market a product consumes 12 years (approximately 71% of patent
      life) and costs more than +250 million. The industry will be well served to
      closely monitor itself through conformance to GCP guidelines and regulations to
      avoid further government regulation.

PMID- 8520868
TI  - FDA's fraud policy and ethical concerns.

PMID- 8520869
TI  - The development and implementation of a quality assurance Master Audit Plan.
AB  - As a quality assurance (QA) department for a clinical research organization, QA
      conducts audit activities for clinical trials managed by our organization and
      acts as an independent QA group for several other companies. A quality
      assurance/regulatory compliance Master Audit Plan is developed for each study or
      each audit if the audit is an independent task. The Master Audit Plan designed
      for a specific clinical study consists of a combination of several QA activities
      designed to ensure quality and regulatory compliance, to define timelines, and to
      identify personnel. These activities may include the review of the regulatory
      documents for each investigative site prior to the shipping of test article (test
      article release), review of informed consent, review of internal sponsor study
      files, and clinical site audits. Results of audit activities conducted under the
      Master Audit Plan for several clinical studies have been compiled for three of
      the major QA tasks. These include test article release, informed consent review,
      and site audits. A review of regulatory document files for test article release
      indicated that 13% required additional documents or correction of submitted
      documents. A review of informed consents found that 32% required revision. Site
      audit activities indicated that the clinical sites were, in general, adhering to
      Federal regulations and GCP guidelines. Observations noted at sites tended to
      fall into the categories of test article accountability issues, regulatory
      document additions or revisions, and quality control issues.

PMID- 8520870
TI  - Implementation of Current Good Manufacturing Practices in a small research
      laboratory setting.
AB  - The Current Good Manufacturing Practice (cGMP) for Finished Pharmaceuticals as
      found in 21 CFR 211 is specifically geared to the regulation of drug
      manufacturing processes in industry. However, under some circumstances, it
      becomes necessary to apply the regulation to manufacturing operations in a
      research laboratory setting. Application of the regulations in such a setting
      requires management commitment, cooperation between QA/QC and technical staff,
      patience, creativity, and an understanding of the spirit behind the letter of the
      law. Breaking down the regulations into their fundamental parts gives insight
      into the intent of the regulations and aids in their application. This article
      will outline our experience in applying the cGMP in a research laboratory
      setting.

PMID- 8520871
TI  - Critical aspects of conducting and auditing GLP studies--the practical
      perspective.

PMID- 8520872
TI  - The Sacred Heart Hospice: an Australian centre for palliative medicine.
AB  - The Sacred Heart Hospice, Sydney, was founded in 1890 and is the largest
      inpatient palliative-care facility in Australia. Patients with advanced cancer
      form the predominant patient group, although patients with HIV/AIDS account for
      approximately 20% of admissions. A community-outreach service, established in
      1983, cares for more patients at home than in the Hospice. Recently the Hospice
      has participated in a number of clinical trials and intends to become a regional
      centre for palliative-care research, education and training.

PMID- 8520873
TI  - The role of serotonin as a mediator of emesis induced by different stimuli.
AB  - The aim of this work was to evaluate the impact of changes in serotonin
      metabolism on the pathophysiology of different types of emesis: pregnancy-induced
      emesis, emesis associated with inner-ear dysfunction, and cisplatin-induced
      emesis. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main
      metabolite of serotonin, was measured in 13 women with pregnancy-induced emesis,
      12 patients who had nausea and vomiting following inner-ear dysfunctions, 27
      patients with cisplatin-induced emesis and a control group of 21 women. 5-HIAA
      was measured with a fluorescence polarization immunoassay (Abbott) and corrected
      for varying urine concentrations. Both patients with emesis associated with inner
      ear dysfunction and patients with pregnancy-associated emesis showed a similar 5
      HIAA excretion pattern compared with the control group. No correlation between
      intensity of nausea or vomiting and changes in 5-HIAA excretion could be
      detected. In patients receiving cisplatin, the 5-HIAA excretion increased rapidly
      within the 12 h following cisplatin administration and returned to baseline
      levels after 24 h. There was a parallel increase of 5-HIAA excretion and numbers
      of emetic episodes in the first 12 h, but delayed emesis was not associated with
      elevated 5-HIAA excretion. Our results provide evidence that serotonin is
      involved in the pathophysiology of cisplatin-induced acute emesis. Cisplatin
      induced delayed emesis, pregnancy-associated emesis, and emesis due to inner-ear
      dysfunction are not associated with elevated levels of 5-HIAA excretion. The
      serotonin pathway probably represents only one of many different afferent
      mechanisms capable of initiating the emesis cascade.

PMID- 8520874
TI  - Early tracheotomy in neutropenic, mechanically ventilated patients: rationale and
      results of a pilot study.
AB  - Despite substantial advances in the management of such patients, the prognosis of
      ventilated neutropenic patients remains grim. The objective of our study was to
      evaluate the benefit of tracheotomy in this category of patients, in terms of
      mortality while they were in the intensive-care unit and nosocomial pneumonias.
      The charts of 53 consecutive, ventilated, neutropenic patients, or those destined
      to be imminently neutropenic, admitted to our intensive-care unit during a 4-year
      period, have been retrospectively reviewed. Tracheotomy was performed at the
      bedside or in the operating room: 20 patients underwent tracheotomy within 48 h
      of mechanical ventilation (ET group), while 33 were tracheotomized later or
      remained intubated (INT group). The two groups were comparable with regard to the
      underlying disease, respiratory failure, mechanical ventilation patterns and
      severity scores, but neutropenia was more profound in the ET group. Mortality
      while in the intensive-care unit was similar (ET: 70%; INT: 78.8%). However, the
      survival curves showed a trend towards longer survival in the ET group, even
      after adjustment for the degree of neutropenia (log-rank test: P = 0.07). The
      incidence of pneumonias was similar in both groups. No major complications of
      tracheotomy were reported. These findings suggest that a tracheotomy could be
      proposed for neutropenic patients requiring mechanical ventilation, in order to
      prolong their survival beyond the end of the neutropenic period. A prospective
      study is underway to confirm these preliminary results.

PMID- 8520875
TI  - Totally implanted catheters to reduce catheter-related infections in patients
      receiving interleukin-2: a 2-year experience.
AB  - A high incidence of bacterial infections has been previously reported during
      interleukin-2 (IL-2) treatment, mainly due to catheter-related infections.
      Antibiotic prophylaxis has been successfully used to decrease such infections.
      The goal of this study was to evaluate an alternative way to reduce catheter
      related infections in IL-2-treated patients by the use of totally implanted
      catheters. A total of 74 patients with metastatic renal cell carcinoma, referred
      to our institution to receive IL-2 from March 1989 to July 1991, were included in
      this prospective study. IL-2 was given on a 2-days-a-week schedule (24 x 10(6) IU
      m-2 day-1) either alone (41 patients) or in association with interferon gamma (33
      patients). All these patients were prospectively evaluated for fever, bacteremia
      and line-site infection. Seven patients (9.5%) had one (2 patients) or more (5
      patients) positive blood cultures with Staphylococcus aureus. Antibiotics were
      used only in 5 patients, and the catheter had to be removed in only 2 of these
      patients. In the other patients, no further infection developed despite the lack
      of antibiotics. Moreover, 9 patients had positive blood cultures with
      Staphylococcus epidermidis (1.9% of total number of blood cultures). In
      conclusion, a totally implanted catheter appears to reduce the incidence of
      infections in IL-2-treated patients, at least on a 2-days-a-week schedule.

PMID- 8520876
TI  - A phase II study of ondansetron as antiemetic prophylaxis in patients receiving
      high-dose polychemotherapy and stem cell transplantation.
AB  - The field of high-dose chemotherapy with stem cell transplantation has been
      expanded recently as a treatment for solid tumors and hematological malignancies.
      Severe emesis remains one of the main extramedullary side-effects of high-dose
      regimens during the first week of treatment. Traditional antiemetics such as
      chlorpromazine, diazepam, and phenothiazines are extensively used but are unable
      to control emesis. The new antiemetic ondansetron, a serotonin receptor (5HT3)
      antagonist appears to be superior to these drugs for cisplatin-induced emesis.
      The study we present here is an attempt to control emesis following high-dose
      regimens, during bone marrow or peripheral stem cell transplantation, with
      ondansetron. To our knowledge no other paper has reported the efficacy of this
      antiemetic in such group of patients. A total of 29 patients who received highly
      emetogenic polychemotherapy as conditioning regimens for bone marrow
      transplantation were treated with ondansetron, which was given as an 8-mg i.v.
      short infusion prior the initiation of treatment and every 6 h thereafter for 3
      days, and an 8-mg dose every 8 h for 5 additional days. All the patients had
      previously been treated with chemotherapy and were evaluable for response and
      toxicity. Complete and major protection of vomiting on day 1 was achieved by 76%
      of the patients, 58% on day 2 and 52% on day 3. Nausea was absent or mild in 79%
      of patients on day 1, 45% on day 2 and 41% on day 3.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8520877
TI  - Dexamethasone improves the efficacy of granisetron in the first 24 h following
      high-dose cisplatin chemotherapy.
AB  - The object of the study was to determine whether dexamethasone improved the
      efficacy of the serotonin receptor (5-HT3) antagonist granisetron in controlling
      acute (within 24 h) emesis in cancer patients receiving high-dose cisplatin
      chemotherapy and to ascertain whether continuation of granisetron after 24 h
      reduces the occurrence of delayed emesis. This randomised, double-blind,
      multicentre, three-arm study was conducted at 21 medical centres. A group of 292
      nausea- and emesis-free patients with cancer, who had never had chemotherapy and
      were scheduled to receive at least 50 mg/m2 cisplatin, were given 3 mg
      granisetron i.v. in a 15-min infusion with or without 10 mg dexamethasone i.v.
      completed 5 min prior to high-dose cisplatin and 1 mg granisetron p.o. at +6 h
      and +12 h. Primary study end-points were control of emesis and nausea. Patients
      completed a self-report diary every 6 h for the first 24 h. At the end of the 24
      h period, the patients who received dexamethasone had a significantly higher
      complete protection rate from emesis (64% compared to 39%) than those who
      received no steroid. Similarly, the dexamethasone-treated group had a
      significantly higher complete plus partial (0-2 emetic episodes) protection rate
      (84% compared to 64%). This study shows that dexamethasone markedly enhances the
      antiemetic efficacy of granisetron for acute-onset emesis in high-dose cisplatin
      chemotherapy.

PMID- 8520878
TI  - Abdominal wall metastasis following percutaneous endoscopic gastrostomy.
AB  - Percutaneous endoscopic gastrostomy (PEG) has become a widely used method for
      nutritional support, particularly in patients with advanced head and neck
      carcinomas. Since the method is easy and widely established it is necessary to
      assess possible complications, even rare ones. In this paper we report on two
      patients with vaccination metastasis following PEG insertion. Both patients had
      advanced squamous cell carcinoma of the head and neck or the upper esophagus. In
      three patients previous bougienage was performed, because of considerable
      stenosis of the pharynx and/or esophagus. Fast-growing metastases were found at
      the site of PEG insertion, with and without involvement of the gastric wall. In
      neither case was abdominal wall metastasis the cause of death. There is a small
      but definite risk of tumor seeding into the abdominal wall after PEG insertion
      for obstructive malignant tumors. The clinical impact of this finding, however,
      is still undefined and needs further investigation.

PMID- 8520879
TI  - Asthma associated with small-cell lung cancer.
AB  - Bronchial asthma due to small-cell carcinoma is very rare and reports in the
      literature are few. This paper reports such a case. Asthma was the only
      noteworthy clinical manifestation of admission. More detailed examination,
      undertaken because the patient failed to respond to bronchodilator therapy,
      revealed a pulmonary carcinoma. The bronchoconstriction responded only to
      octreotide therapy.

PMID- 8520880
TI  - Prophylaxis of streptococcal bacteraemia with oral penicillin V in children
      undergoing bone marrow transplantation.
AB  - The work described aimed to evaluate the incidence of streptococcal bacteraemia
      in children undergoing bone marrow transplantation and receiving prophylaxis with
      penicillin V. From January 1991 to December 1993 oral penicillin V was
      administered as prophylaxis for streptococcal bacteraemia to patients undergoing
      bone marrow transplantation at G. Gaslini Children's Hospital, Genoa, Italy. The
      data were compared with those from a similar population receiving bone marrow
      transplantation from September 1984 to July 1990 and not receiving this kind of
      prophylaxis. Streptococcal bacteraemia was diagnosed in 7/17 (41%) episodes of
      bacteraemia observed in the period January 1991 to December 1993, while it
      accounted for 71% of all bacteraemias in the period from September 1984 to July
      1990 and was especially frequent from January 1988 to July 1990, comprising 13/15
      (87%) of observed bacteremias. The decrease of this complication observed after
      the beginning of the prophylaxis programme was statistically significant. Oral
      penicillin V is effective as prophylaxis of streptococcal bacteraemias in
      children receiving bone marrow transplantation in a centre with a high incidence
      of this complication.

PMID- 8520881
TI  - Have enteric infections a role in 5-fluorouracil-associated diarrhea?
AB  - In 16 advanced colorectal cancer patients with 5-fluorouracil-associated
      diarrhea, we evaluated the role of bacterial pathogens in the development of this
      adverse effect. Neither Clostridium difficile nor other pathogens were cultured
      from fecal specimens. These data seem to suggest that it is unlikely that
      intestinal infections have a role in the pathogenesis of 5FU-associated diarrhea.

PMID- 8520883
TI  - "Cancer and quality of life".

PMID- 8520882
TI  - Immune-complex glomerulonephritis associated with Staphylococcus aureus infection
      of a totally implantable venous device.
AB  - We report a previously unrecognized complication of totally implanted
      subcutaneous ports. A patient with a totally implantable central venous device
      developed a septic syndrome. Blood and injection-reservoir cultures grew
      Staphylococcus aureus. There was no evidence of endocarditis. The port was
      removed but acute oliguric renal failure developed. A percutaneous renal biopsy
      showed acute diffuse proliferative glomerulonephritis. There was no
      extracapillary crescent. On immunofluorescence study, capillary wall granular
      deposits stained brightly for IgG and C3. These findings were thought to be
      consistent with infection-associated immune-complex glomerulonephritis.

PMID- 8520884
TI  - Anchorage and release of Gram-positive bacterial cell-surface polypeptides.

PMID- 8520885
TI  - Whole genome sequencing of pathogens: a new era in microbiology.

PMID- 8520886
TI  - CD46-mediated measles virus entry: a first key to host-range specificity.
AB  - Humans are the sole natural host of measles virus. The identification of CD46 as
      a virus receptor and of the involvement of moesin sheds some light on the
      molecular events occurring during virus entry into the cell. Knowledge of the key
      role of CD46 paves the way to creating transgenic mice sensitive to measles virus
      infection.

PMID- 8520887
TI  - Budding of alphaviruses.
AB  - The icosahedral structures of alphaviruses and of the external shell of the viral
      nucleocapsid have been defined to very high resolutions, revealing details of the
      interactions between the glycoproteins to form trimeric spikes and the
      nucleocapsid. The structural studies complement biochemical and molecular genetic
      studies showing that a sequence-specific interaction between the cytoplasmic
      domains of the glycoproteins and the nucleocapsid drives budding.

PMID- 8520888
TI  - Pseudomonas aeruginosa, mucoidy and the chronic infection phenotype in cystic
      fibrosis.
AB  - During chronic infections in cystic fibrosis, persistence of Pseudomonas
      aeruginosa is associated with conversion into forms that are associated with
      conversion into forms that are characterized by a mucoid colony morphology, rough
      lipopolysaccharide and, paradoxically, decreased systemic virulence. The
      mutations underlying these changes occur in global regulators, such as
      alternative sigma factors and their accessory elements.

PMID- 8520889
TI  - Immune escape and tropism of HIV.
AB  - HIV-1 cell tropisms are partly determined by the hypervariable loops V1/V2 and V3
      in gp120, which also contain epitopes for neutralizing antibodies. Mutations
      conferring tropism changes can result in escape from neutralization and vice
      versa. We examine whether variant viruses that can colonize new cell types and
      simultaneously escape neutralizing antibodies have an enhanced advantage in vivo.

PMID- 8520890
TI  - Measles virus replication in neural cells.
AB  - Measles virus gene expression is attenuated in neural cells by mechanisms that
      affect both viral transcription and translation. Host enzymes that hypermutate
      viral genes, and those induced by cytokines, may act cooperatively to slow viral
      replication and to favor persistent measles virus infections in the human central
      nervous system.

PMID- 8520891
TI  - [Role of characteristics of the bronchopulmonary structure in the etiology of
      occupational diseases of the respiratory organs].
AB  - The article analyzes the role of bronchial and pulmonary anatomy in formation if
      occupational diseases--chronic bronchitis and pneumoconiosis. Those diseases in
      over 78% of the examinees appear on the background of various anomalies of
      bronchial and pulmonary structure. In this case congenital anomalies commonly
      coincide with abnormal segmentary division of bronchi and extend down to the
      terminal parts of airways. Over 70% of the patients demonstrate tracheobronchial
      dyskinesia being an important cause of the diseases' fast progressing.

PMID- 8520892
TI  - [Prevalence of dyslipoproteinemia in a sample of men living in urban and rural
      areas].
AB  - Changes of serum lipoprotein levels were classified in random selects of male
      donors aged 20-59, living in Ufa (370 examinees) and Bashkirian rural center (130
      examinees). The examinees of Ufa appeared to have hyperalpha- (6.8%), hypoalpha-
      (6.3%), combined hyperalpha- and hypobeta- (0.9%), hypobetalipoproteinaemia
      (2.7%), IIa (6.3%), IIb (2.3%) and IV (5.0%) types of hyperlipoproteinaemia,
      cholesterol and/or triglycerid levels were within normal limits (4.5%). The
      examinees of the rural center were diagnosed as having hyperalpha- (2.3%),
      hypoalpha- (6.1%), combined hyperalpha- and hypobeta- (0.8%), IIa (3.8%), IIb
      (7.7%) types of hyperlipoproteinaemia. The article covers discussion on influence
      of antropogenous environment on formation of dyslipoproteinaemia phenotypes.

PMID- 8520893
TI  - [Grounds of the duration of work shift for female vegetable growers working in
      the field in the summer].
AB  - Analysis of changes in heat state of female vegetable-growers within the shift
      helped to determine correlation between microclimate parameters (including
      general indicator of extrinsic heat load--WBGT index) and temperature state in
      the females adjusted and non-adjusted to heat. Depending on various relationships
      between the microclimate parameters inducing variable overheating, duration of
      the working shift is set for stably optimal heat state.

PMID- 8520894
TI  - [Effects of students' work activities in autumn agricultural teams on their
      morbidity].
AB  - The authors used social studies, timing in order to assess organization and work
      conditions of manual cotton harvesting by students. Further analysis covered
      morbidity with transitory disablement among the participants of 8 agricultural
      teams. Manual cotton harvesting appeared to bring intensive physical strain,
      awkward working posture, long trips to carry heavy loads in excessive exposure to
      agrochemical agents. Those hazards induced the growing morbidity. Each third one
      of the examinees faced transitory disablement. The morbidity structure was opened
      by respiratory diseases (25.1% of all the cases and 16.9% of all the disablement
      days), then came gastrointestinal diseases (21.6% and 18.0% respectively), the
      third place was occupied by neurologic illnesses and disorders of sensory organs
      (12.8% and 10.1% respectively). The studies proved the activities estimated as an
      important hazard for the students' health.

PMID- 8520895
TI  - [Occupational causes of erysipeloid morbidity among the workers engaged in meat
      processing industry in the Lugansk region].
AB  - Erysipeloid takes the second place after eczema among other occupational diseases
      at the meat-processing enterprises of Lugansk region. The maximal occurrence is
      seen at the meat enterprises in summer. The morbidity is promoted by slight
      traumatism in cold and humid work conditions. Skin and joints are most frequently
      affected by the disease. One of each four among the sufferers demonstrates the
      prolonged course with longstanding arthropathies.

PMID- 8520896
TI  - [Histomorphological changes in the bronchopulmonary system induced by glass fiber
      dust].
AB  - The article presents materials obtained in experimental study of respiratory
      symptoms in white rats exposed to glass fiber dust. Intratracheal administration
      of the dust resulted in acute obstructive bronchitis by the end of third week of
      exposure. Fibroplastic processes being possible initial signs of pneumofibrosis
      form by the end of the 4th month.

PMID- 8520898
TI  - [Medical prophylaxis of occupational intoxication in polyvinyl chloride
      industry].
AB  - The study covered clinical and laboratory findings, immunity parameters in 103
      workers of polymer compounds production. The individuals exposed to chlorine
      organic chemicals: mercuric vapors, gaseous chlorine demonstrate specific changes
      of metabolic parameters. The data on protein synthesis, monooxygenases activity,
      lipid metabolism, state of membranes (lipoprotein complex, peroxidases, ALa-AT,
      Asp-AT), immune activity enabled to design prophylactic measures. To accomplish
      the therapeutic measures, the department for prevention of occupational
      intoxication is organized in local industrial medical center.

PMID- 8520897
TI  - [Correlation between HLA antigens and immune status in dust-induced lung diseases
      in workers of machine-building industry].
AB  - Simultaneous study of immune state and HLA-testing was conducted for 73 patients
      with pneumoconiosis and 52 sufferers from dust bronchitis. The HLA antigens
      appeared to correlate with immune disorders in those diseases. The study revealed
      differences in the HLA antigens causing immune changes in pneumoconiosis and dust
      bronchitis. Those differences corresponded to differences between the markers of
      propensity to those diseases. Thus, the authors assume that formation of
      pneumoconiosis or dust bronchitis could depend on genetically determined variants
      of immune disorders.

PMID- 8520899
TI  - [Specific problems of occupational diseases in various branches of agricultural
      production].
AB  - Contemporary development of agricultural structures in connection with changes of
      socio-economic relationships complicates the task of health care for rural
      population. Financial difficulties disordered managing and control of ecologic
      situation in rural area. The causal matters include absence of new agricultural
      machinery, chaotic use of agrochemicals purchased abroad, increased occurrence of
      occupational brucellosis and other diseases in animal husbandry farms. The
      authors necessitate effective control provided by industrial medical officers and
      regional sanitary and epidemiologic service to improve work conditions and lower
      morbidity and traumatism in rural territories.

PMID- 8520900
TI  - [Prevalence of allergic diseases in workers of industrial swine breeding].
AB  - The article presents methodic approaches to thorough occupational hygienic
      analysis of allergic diseases. Analyzing allergic morbidity in major swine
      breeding enterprise, the authors give an example of conclusion necessitating
      summary of clinical and immunologic results, analysis of morbidity with
      transitory disablement, hygienic studies orientated to forecast.

PMID- 8520901
TI  - [Use of products made of antimicrobial materials in the prevention of foot
      mycoses].
AB  - Field trials were conducted to evaluate effectiveness of mycoses prophylaxis
      gained by use of antimicrobial insoles and foot-binding with fungicide agents.
      The trials involved 100 novice soldiers. Bacteriology and bacterioscopy studies
      diagnosed 47 soldiers as having subclinical mycosis of feet. Using antimicrobial
      insoles and foot-binding caused considerably lower occurrence of pathogenic fungi
      in the skin samples; using antimicrobial insoles with regular foot-binding
      resulted in no changes of the skin microflora. The authors recommend wide
      application of antimicrobial stuff with fungicide agents for prophylaxis of feet
      mycosis.

PMID- 8520902
TI  - [Method of detecting excitability of skin receptors in the diagnosis of vibration
      disease].
AB  - The follow-up studies of patients with vibration disease caused by local
      vibration proved diagnostic value of minor skin response of dorsal hand surface
      and anterior surface of arm or forearm, if subjected to irritation with mixture
      of chloroform and ethanol. Depressed skin receptors during the disease are
      diagnosed through longer latent period of burning sensation in two of three
      points irritated on skin of the upper limb. The diagnostic method based on
      chemical stimulation of skin receptors is highly sensitive (86.9%) and specific
      (94.4%), especially for early stages of the disease, promoting detection of
      subclinical peripheral neuropathy caused by vibration. Due to its simplicity and
      availability the method could replace algesimetry in mass screening among workers
      exposed to vibration.

PMID- 8520904
TI  - [Clinical-hygienic diagnosis of occupational allergic dermatoses].
AB  - The authors demonstrated productivity of clinical and hygienic differential
      diagnosis of occupational and non-occupational allergic dermatoses. Original
      scheme and methodic approaches enable to precise the etiology and justify
      clinical diagnosis.

PMID- 8520903
TI  - [Experimental studies on the effect of dietary fiber on excretion of copper].

PMID- 8520905
TI  - [Role of electromagnetic irradiation of various frequencies in the etiology of
      hemoblastoses].

PMID- 8520906
TI  - [Evaluation of health status of agricultural machine operators and agriculture
      students].
AB  - To lower morbidity with transitory disablement, to better primary prophylaxis and
      health preservation for machine operators and professional training students, a
      system of therapeutic and sanitary measures is to be put into practice. Those
      measures include improved organization of medical care, better hygienic
      conditions, safe work and healthy lifestyle of the examinees.

PMID- 8520907
TI  - [Reproductive health of the family as a goal of industrial medicine].
AB  - Modern demographic situation stressed the problems of human reproductive health
      associated with industrial medical topics. The article suggests to regard a
      family (child and two parents) as a unit under study in industrial medicine. This
      methodic approach should work in scientific programs reviewing influence of
      industrial ecology and environmental factors on reproductivity. The authors
      suggest elaboration of universal strategy for ecologic and epidemiologic studies
      to form a scientific branch "Epidemiology of reproductive health" and to
      elaborate methods for better health management during the present demographic
      crisis.

PMID- 8520908
TI  - [Use of dispersion analysis in the assessment of combined effect of low levels of
      carbon monoxide and psychoemotional stress in chronic experiment].
AB  - The article deals with evaluation of joint effects by means of dispersion
      analysis. The experimental study covered joint effects caused by low levels of
      carbon oxide (MAC and those 3 times lower) and specific psychoemotional stress in
      white rats. The studied parameters described activities of the central nervous,
      cardiovascular and immune systems. Dispersion analysis helped to reveal
      predominant role of the stress in the joint effects on the cardiovascular and
      central nervous systems, prevalent role of carbon oxide in the joint effects on
      the immune system.

PMID- 8520909
TI  - ["Even", integral indicators in systemic mathematical analysis of fatigue].
AB  - The article considers 3 different points of view on systemic mathematical
      analysis of human fatigue process. In this case, the same physiologic information
      is processed according to various algorithms for integral and digital estimates
      of lowered performance and energy expenditure, as well as indirect
      characteristics of inhibition and excitation processes in the brain cortex. The
      mathematical results are applied in computer forecasting of individual
      occupational risk at the specific workplace.

PMID- 8520910
TI  - [Low doses of ionizing radiation and short- and long-term hematologic changes
      (review of the literature)].

PMID- 8520911
TI  - [Regional and local problems of chemical environmental pollution and health of
      the population (review of the literature)].

PMID- 8520913
TI  - [Treatment of limb paralysis using low-frequency deep electric stimulation].
AB  - To cure various conditions associated with paralysis and internal diseases due to
      occupational poisoning, Chinese doctors apply a method of low-frequency deep
      electric stimulation. Mobility of the limbs restore in 91% of cases. Treatment of
      the internal diseases was 100% effective.

PMID- 8520912
TI  - [Information content of immunologic parameters in the evaluation of the effects
      of hazardous substances].
AB  - Clinical and immunologic examination including 1 and 2 level tests covered 429
      staffers of chemical enterprises and 1122 of those engaged into microbiological
      synthesis of proteins, both the groups exposed to some irritating gases and
      isocyanates. Using calculation of Kulbak's criterion, the studies selected
      informative parameters to diagnose immune disturbances caused by occupational
      hazards. For integral evaluation of immune state, the authors applied general
      immunologic parameter, meanings of which can serve as criteria for early
      diagnosis of various immune disorders and for definition of risk groups among
      industrial workers exposed to occupational biologic and chemical hazards.

PMID- 8520914
TI  - [Thermographic signs of forearm myopathies in industrial workers].
AB  - The authors described thermographic sign of forearm myopathy similar to RSI in
      industrial workers. The sign is that upper third of the forearm has skin
      temperature higher by over 0.3 degree C (for associated cervical osteochondrosis-
      by over 0.5 degree C) as lower third of the forearm. The temperature gradient (up
      to 2.5 degrees C) appeared to correlate with more marked myopathy.

PMID- 8520915
TI  - [Increase of human resistance to the effects of high ambient temperatures by
      using drugs].

PMID- 8520916
TI  - [Influence of pilot's mental state on the quality of his professional
      activities].
AB  - The studies defined main factors influencing psychic state and occupational
      reliability of pilots. Those factors are conflicts in professional, business and
      family relationships and health disorders, especially psychogenic ones. Lower
      occupational reliability is an early sign of psychologic confusion, so the
      factors mentioned could serve for diagnosis of premorbid psychogenic conditions
      in pilots, for evaluation of their professional validity.

PMID- 8520917
TI  - [Adrenergic reactivity of cell membranes as a criterion of occupational health of
      pilots].

PMID- 8520918
TI  - [Features of changes in psychophysiological state of operators exposed to high
      temperatures].
AB  - Having analyzed the scientific materials, the author stresses the absence of
      unified theory on psychophysiologic changes caused in operators by high ambient
      temperatures. The personal research proved that high ambient temperatures (45-60
      C with humidity at 10-15%) cause worse psychophysiologic state of operators since
      beginning of the exposure. The author considers that it could result from excess
      of the skin weighted average temperature over the rectal one. That is
      characteristic for the operator performing no physical work. Other feature of the
      temperature state is compromised "temperature image" integrating temperatures of
      the skin, blood, viscera and hypothalamus for better homeostasis.

PMID- 8520919
TI  - [Theory and practice within the framework of pharmaceutical education].
AB  - The present paper deals with the problems of the graduate study of pharmacy with
      regard to the relationship of theoretical and practical teaching. The situation
      in Slovakia is discussed and compared with the present-day states in some
      countries of Western Europe.

PMID- 8520920
TI  - [Drug forms for drug delivery into the gastrointestinal tract].
AB  - Most drugs introduced into the GIT are absorbed into the stomach and/or the small
      intestine according to their chemical character. Some drugs (their number is on
      the increase) require targeted supply to a certain site in the GIT if their
      biological activity is to be manifested and made use of. Fulfilling this
      condition, which concerns primarily peptides and proteins, requires adjustments
      of dosage forms. Much effort is put forth to shift absorption into the large
      intestine (colon), which is advantageous from the viewpoint of circadian
      biorhythms.

PMID- 8520921
TI  - [Phytotherapeutic aspects of diseases of the cardiovascular system. 5. Saponins
      and possibilities of their use in prevention and therapy].
AB  - The summarizing paper deals with the structure and biological effects of saponins
      generally and in relation with the treatment and prevention of diseases of the
      heart and circulatory system. In this field, mainly the saponins from the plants
      of the genera Panax, Gynostemma or Bupleurum are of use. Also soya saponins and
      saponins of the genera Astragalus, Salvia, Boussigaultia and Litchi can be
      employed. Saponins exert a positive effect on the function of the heart direct,
      or they help treat related diseases. For instance, they inhibit the formation of
      lipid peroxides in the cardiac muscle or in the liver, they influence the
      function of enzymes contained in them, they decrease blood coagulation,
      cholesterol and sugar levels in blood, they stimulate the immunity system. They
      act either direct, blocking the transfer of Ca2+ ions or modulating the function
      of Na(+)-K(+)-ATPase, or they help resorb other active principles. It can be
      concluded that saponins are a prospective group of drugs of natural origin for
      the prevention and treatment of diseases of the heart and circulatory system.

PMID- 8520922
TI  - [Pharmacologic control of reperfusion dysrhythmias].
AB  - The present study aims to investigate the effects of the lipophilic antioxidant
      Trolox C (a vitamin E analogue) and stobadine, a scavenger of free oxygen
      radicals, on reperfusion dysrhythmias. Experiments were performed on isolated
      perfused rat hearts subjected to global stop-flow ischaemia followed by
      reperfusion. Trolox C (10(-4 mol.l-1) and stobadine (10(-5) mol.l-1) were infused
      immediately prior to ischaemia. Trolox C (10(-4) mol.l-1) and stobadine (10(-5)
      mol.l-1) decreased the incidence and duration of reperfusion-induced dysrhythmias
      (quantified by the dysrhythmia score) in comparison to the ischaemic-reperfusion
      damaged hearts. There was an improvement in the recovery of contraction force and
      left ventricular diastolic pressure in Trolox or stobadine pretreated hearts. No
      significant changes in coronary flow resistance were observed. The results
      suggest that both substances protect the myocardium during ischaemic-reperfusion
      injury probably by affecting the generation and activity of reactive oxygen
      species.

PMID- 8520923
TI  - [Preparation of aryloxyaminopropanol derivatives with potential effects on the
      cardiovascular system].
AB  - The synthesis of nine compounds belonging to the group of aryloxyaminopropanols
      with carbamate substitutions of the aromatic ring is described and
      pharmacologically evaluated. The results suggest that an addition of N-phenyl
      piperazine derivatives to the main basic moiety can exert a positive influence on
      their beta-adrenolytic, antiarrhytmic or antihypertensive activity.

PMID- 8520924
TI  - [The effect of quaternization on local anesthetic effects of trimecaine].
AB  - Effects of the local anaesthetic trimecaine and its quaternary derivative on the
      isolated rat sciatic nerves were examined. Trimecaine inhibited action potential
      propagation in the isolated nerve in vitro at four-times lower concentrations
      than its quaternary derivative. Despite extracellular application, the quaternary
      derivative inhibited action potential propagation in the sciatic nerve but with a
      longer half-life in comparison with trimecaine. With increasing external pH, the
      blocking effect of trimecaine was profound. The blocking potency of the
      quaternary compound was not consistently changed with the changes in external
      medium pH.

PMID- 8520925
TI  - [Free oxygen radicals in the pathogenesis of ischemic-reperfusion heart damage
      and possibilities of its pharmacologic control].
AB  - Due to their molecular configuration, most free radicals are highly reactive and
      can cause cell injury. The present review deals with the role of oxygen-free
      radicals (OFR) in the pathogenesis of the heart disease and reperfusion injury.
      Cellular protection against deleterious effects of OFR is organized at multiple
      levels. Regulation of the antioxidant capacity includes not only the maintenance
      of adequate levels of antioxidants but the localisation of antioxidant compounds
      and enzymes as well. Synthetic antioxidants may mimic biological defence
      mechanisms.

PMID- 8520926
TI  - Anaerobic biodegradation potentials in digested sludge, a freshwater swamp and a
      marine sediment.
AB  - An anaerobic gas production test was used for determining the potential
      biodegradation of 22 organic chemicals under methanogenic conditions. Nine of the
      examined chemicals were extensively mineralized (> 75%) both in sewage sludge and
      in a freshwater swamp indicating good agreement between biodegradation potentials
      in these habitats. Samples from a marine sediment showed a less extensive
      mineralization of most of the test chemicals, and lag periods of several weeks
      often preceded net gas production. As marine sediments usually contain sulfate at
      the time of collection, the assessment of biodegradation potentials in such
      environments is probably more reliable when using a method based on sulfate
      reduction instead of methanogenic gas production. The results of the tests
      indicate that the commonly recommended washing of sludge solids can be eliminated
      by applying a more diluted inoculum.

PMID- 8520927
TI  - Polychlorinated diphenyl ethers, dibenzo-P-dioxins and dibenzofurans in Finnish
      human tissues compared to environmental samples.
AB  - Finnish human samples from the Helsinki area and Arctic cod samples from
      Vestertana Fjord (Norway) were analyzed for polychlorinated diphenyl ethers
      (PCDE) and 2,3,7,8-chloro substituted dibenzo-p-dioxins (PCDD) and dibenzofurans
      (PCDF). The PCDE, PCDD and PCDF contents in human and animal samples from Finland
      and elsewhere were briefly reviewed. PCDEs were non-detectable in human liver and
      testis, but some PCDE congeners were identified in human adipose tissue and fat
      of boiled Arctic cod liver composite. The contents of PCDEs in Finnish human
      samples were similar to those reported in the literature for human tissues from
      North America. The estimated concentrations of PCDEs 99, 147 + 153 (coeluting)
      and 206 ranged between 2 and 8 ng/g lipid weight (lw) in one Finnish human
      adipose tissue. The concentrations of PCDE congeners identified in the cod liver
      fat were between 0.4 and 5 ng/g lw. Of toxic PCDDs and PCDFs, hepta- and octa
      CDDs dominated in human. The concentrations of PCDD and PCDF congeners varied
      from < 2 to 7700 pg/g lw in human. In Arctic cod samples analyzed (muscle tissues
      of an air dried cod and cod liver fat), 2,3,7,8-tetra-CDF was nearly the only
      congener of PCDD/PCDFs detected.

PMID- 8520928
TI  - Perinatal exposure to polychlorinated biphenyls and dioxins through dietary
      intake.
AB  - Polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins
      and dibenzofurans) are potentially hazardous compounds. Since food is the major
      source (> 90%) for the accumulation of PCBs and dioxins in the human body, food
      habits in women determine the degree of fetal exposure and levels in human milk.
      In order to investigate an association between dietary intake and PCB and dioxin
      levels in human milk and PCB levels in maternal and cord plasma, the food intake
      of 418 Dutch women during pregnancy was recorded using semi-quantitative food
      frequency questionnaires. After adjusting for covariates, a weak association was
      found between the estimated dietary intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (2,3,7,8-TCDD), dioxins, and planar PCBs and their corresponding levels in breast
      milk. The estimated dietary intake of 2,3,7,8-TCDD, dioxins, and planar PCBs was
      also related to the PCB levels in maternal and cord plasma. Dairy products
      accounted for about half and industrial oils for about a quarter of the estimated
      2,3,7,8-TCDD, dioxin, and the planar PCB intake. It is concluded that the
      contribution of a pregnancy related diet to PCB and dioxin levels in human milk
      and to PCB levels in maternal and cord plasma is relatively low. Decrease of
      exposure to PCBs and dioxins of the fetus and the neonate probably requires long
      term reduction of the intake of these pollutants. Substitution of normal cheese
      by low-fat cheese and the use of vegetable oils instead of fish oils in the
      preparation of foodstuffs by the food industry could contribute to a reduced
      intake of PCBs and dioxins.

PMID- 8520929
TI  - Short term fasting does not aggravate immunosuppression in harbour seals (Phoca
      vitulina) with high body burdens of organochlorines.
AB  - Two groups of 11 harbour seals (Phoca vitulina) with different body burdens of
      organochlorines were subjected to an experimental 15-day fasting period, during
      which they lost an average 16.5% of their body weights. Blood levels of the most
      persistent organochlorines showed an approximate twofold increase, while levels
      of aryl hydrocarbon receptor-binding organochlorines remained largely unaffected.
      Few differences in immunological parameters were observed between the two dietary
      groups. Numbers of circulating lymphocytes dropped to about 65% of the initial
      values and NK cell activity showed a slight increase in both groups. Mitogen- and
      antigen-induced lymphoproliferative responses of the Baltic group of seals
      remained within normal ranges. These results suggest that relatively short-term
      fasting periods do not present an additional immunotoxicological risk to seals
      with high body burdens of organochlorines.

PMID- 8520930
TI  - Correlation of physicochemical properties of alkylphenols with their graph
      theoretical epsilon parameter.
AB  - For a series of 40 alkylphenols, the graph-theoretical parameter epsilon
      correlates very closely with physicochemical parameters of interest in predicting
      environmental toxicity and fate, and especially with logKOW (r = 0.998). Possible
      uses of this correlation are discussed, along with needs for extending the
      epsilon parameter to other types of molecules.

PMID- 8520931
TI  - The octavolateralis system and Mauthner cell: interactions and questions.
AB  - This paper is an overview of some of the major points to arise in the
      accompanying contributions of this special symposium issue. The symposium papers
      arose out of discussions among investigators interested in the inner ear and
      Mauthner cell, with the focus on hydrodynamic components that activate the
      Mauthner cell through the octavolateralis system. The intention of the symposium
      was to investigate the possibility of using our knowledge of the Mauthner system
      to help understand acoustic processing by the ear, and of using our knowledge of
      fish hearing to better understand Mauthner cell function. This is the first
      attempt to take a broad look at both systems to see how they might function
      together. As such, these proceedings can serve as a mini-tutorial for
      investigators interested in one system or the other. In this summary paper we
      also identify some of the major uncertainties in our understanding of the ear
      Mauthner connection. These include questions about: (1) the identity of the
      acoustic stimuli that are neuroethologically relevant to the Mauthner system; (2)
      the relative importance of the various octavolateralis inputs (acoustic,
      vestibular, or lateral line); (3) the contribution of the different various
      acoustic endorgans to the Mauthner system; (4) whether the Mauthner system can
      distinguish sound source location, and (5) whether Mauthner neurobiology is
      compatible with the prevailing model (the phase model) for determining sound
      source location by fishes. We believe these issues provide potentially useful
      avenues of future investigation that should give important insights in both
      acoustic processing by fish and the function of the mauthner system.

PMID- 8520932
TI  - Structural diversity in the inner ear of teleost fishes: implications for
      connections to the Mauthner cell.
AB  - A body of literature suggests that the Mauthner cell startle response can be
      elicited by stimulation of the ear. While we know that there are projections to
      the M-cell from the ear, the specific endorgan(s) of the ear projecting to the M
      cell are not known. Moreover, there are many reasons to question whether there is
      one pattern of inner ear to M-cell connection or whether the endorgan(s)
      projection to the M-cell varies in species that have different hearing
      capabilities of hearing structures. In this paper, we briefly review the
      structure of fish ears, with an emphasis on structural regionalization within the
      ear. We also review the central projections of the ear, along with a discussion
      of the limited data on projections to the M-cell.

PMID- 8520933
TI  - Physiology of primary saccular afferents of goldfish: implications for Mauthner
      cell response.
AB  - Mauthner cells receive neurally coded information from the otolith organs in
      fishes, and it is most likely that initiation and directional characteristics of
      the C-start response depend on this input. In the goldfish, saccular afferents
      are sensitive to sound pressure (< -30 dB re: 1 dyne cm-2) in the most sensitive
      frequency range (200 to 800 Hz). This input arises from volume fluctuations of
      the swimbladder in response to the sound pressure waveform and is thus
      nondirectional. Primary afferents of the saccule, lagena, and utricle of the
      goldfish also respond with great sensitivity to acoustic particle motion (< 1
      nanometer between 100 and 200 Hz). This input arises from the acceleration of the
      fish in a sound field and is inherently directional. Saccular afferents can be
      divided into two groups based on their tuning: one group is tuned at about 250
      Hz, and the other tuned between 400 Hz and 1 kHz. All otolithic primary afferents
      phaselock to sinusoids throughout the frequency range of hearing (up to about 2
      kHz). Based on physiological and behavioral studies on Mauthner cells, it appears
      that highly correlated binaural input to the M-cell, from the sacculi responding
      to sound pressure, may be required for a decision to respond but that the
      direction of the response is extracted from small deviations from a perfect
      interaural correlation arising from the directional response of otolith organs to
      acoustic particle motion.

PMID- 8520934
TI  - Comparative studies on the Mauthner cell of teleost fish in relation to sensory
      input.
AB  - Most physiological and behavioral studies of the Mauthner cells have used the
      goldfish and a few other fish from the superorder Ostariophysi, series Otophysi
      (= otophysans). We first provide some background and recent findings on the
      Mauthner cells of otophysan fish and then compare this information to that known
      about the Mauthner cells in certain non-otophysan fish. These comparisons are
      meant to provide the impetus for a comparative approach to understanding the role
      of the Mauthner cells in behavior.

PMID- 8520936
TI  - Heroes.

PMID- 8520935
TI  - Left-right discrimination of sound onset by the Mauthner system.
AB  - We present a neural model for how the Mauthner system could compute the direction
      of a transient sound stimulus originating on either the left or right side of a
      fish. This computation results in an initial orientation of an escape response
      away from the side of the stimulus. Our idea is based on the phase model of
      underwater sound localization by fishes. If the phase model is applicable to the
      Mauthner system, then the problem of sound localization can be reduced to a
      logical operator, the EXCLUSIVE-NOR (or XNOR). We show how this can be solved by
      the Mauthner system using afferents that convey separate inputs of sound pressure
      transduced by the swimbladder (rarefaction and compression) and particle
      displacement (left and right) from the inner ear. In our model, both pressure
      components are responsible for bringing the Mauthner cell to threshold. Mauthner
      firing is gated by the inhibitory PHP neurons receiving specific combinations of
      pressure and displacement that implement the XNOR logic. We refer to this as the
      XNOR model. This model is experimentally verifiable and makes specific
      predictions about the expected acoustic response characteristics of the Mauthner
      and PHP neurons. Our model places a component of PHP function into a new
      neuroethological context and may provide insights into the central
      neurophysiological mechanisms of directional hearing in fishes. In particular, we
      show how the XNOR model can be applied to predict the activity of diverse neural
      elements involved in acoustic localization by fishes.

PMID- 8520937
TI  - Paediatric trauma--the care of Anthony.
AB  - Trauma causes more than 50% of the deaths in children under the age of 16 years.
      The leading cause is road traffic accidents with children being involved as
      passengers, pedestrians or bicycle riders (Brown et al 1993). When a paediatric
      trauma patient arrives in the Accident and Emergency department it is usually met
      with trepidation and anxiety. The care of the paediatric trauma victim follows
      the same protocols and procedures as with an adult. The primary survey consists
      of airway with cervical spine control, breathing, circulation with haemorrhage
      control, disability and exposure. The secondary survey consists of a head-to-toe
      examination. There are certain differences between children and adults, and
      children should never be considered as little adults. This article covers the
      primary survey and highlights the essential differences between adult and
      paediatric trauma care.

PMID- 8520938
TI  - Getting the right ambulance to the right patient at the right time.
AB  - This paper outlines recent developments in dispatching ambulances according to
      the clinical needs of the patient. Criteria Based Dispatch (CBD) uses accurate
      and effective interrogation of the caller, with reference to clinically approved
      guidelines, to ensure that the appropriate level of ambulance support is
      deployed. The pattern of calls in Glasgow, UK, was monitored in order to evaluate
      CBD in this context, and the potential benefits of adopting the system are
      summarised.

PMID- 8520939
TI  - Research into research practice.
AB  - Since the Briggs report of 1972, the debate over whether nursing is a researched
      based profession continues. This paper attempts to establish whether research
      performed by practitioners in their own field is being directly utilised in
      practice. The paper describes a small scale study of registered nurses (n = 22)
      who have completed the Professional Studies 2 Accident & Emergency module,
      focusing on the utilisation of their action research and the factors influencing
      the outcome of its use. Data was collected by self-report questionnaire. The
      results of the study indicate that many action research projects are not being
      formally utilised within the clinical area. The main factor stated is the lack of
      research culture within units, underpinned by a lack of managerial and peer
      support for research studies. Despite this, research is being utilised, but only
      by the individuals who conducted it. The results suggest that greater integration
      between the college of nursing, management and the student is required to improve
      research utilisation in the clinical area.

PMID- 8520940
TI  - Components of life model in practice.
AB  - This paper attempts to cover the stages recognised as being part of the research
      process in order to investigate the problem related to the lack of individualised
      patient care documentation and supporting theoretical framework, which is both
      understood and accepted by the staff within Accident and Emergency (A & E). With
      the advent of the United Kingdom Central Council's (UKCC) document Standards of
      Record Keeping (1993), there is now greater need for a model to be implemented
      and accepted by those working in the department. The Components of Life model was
      introduced following a literature search, as this seemed to be a potential
      solution to the problem, since it emphasises the individual practising self-care
      activities in order to maintain independence. To initiate staff to the Components
      of Life model, a half study day was organised on the subject of models of care
      within A & E. Jones was invited to discuss his approach to A & E nursing care.
      Subsequently, a draft document relating to nursing care was created using the
      Components of Life model as a framework. The initial draft was followed with a
      printed document which was put into use for a trial period of 4 weeks, followed
      by a review. The review collected both positive and negative comments from the
      staff, the negative proved to be the most constructive as they served to make
      improvements within the care plan. Perhaps the most important success as a result
      of completing this project is that of increased staff enthusiasm and motivation-
      especially in wanting to make the documentation work.

PMID- 8520941
TI  - Triage: a literature review 1985-1993.
AB  - Following an extensive literature review of Accident and Emergency (A & E)
      nursing from 1985-1993, the authors focused upon triage. A wide range of issues
      related to triage and its use in A & E departments are examined. An appendix is
      included to clarify major research finds in this area. Many of the claims made
      regarding triage require further investigation.

PMID- 8520942
TI  - Administration of thrombolytic therapy to patients with acute myocardial
      infarction.
AB  - The publication of large randomised trials such as ISIS 2 (1988) and AIMS (1990),
      provided striking evidence as to the effectiveness of thrombolytic therapy in
      reducing early mortality and morbidity in patients suffering acute myocardial
      infarction. This article will provide an overview of the use of thrombolytic
      agents in modern cardiac care, with particular reference to their impact on the
      Accident and Emergency department.

PMID- 8520943
TI  - A trauma centre in the UK: the Stoke experience.
AB  - This paper outlines the development of a pilot trauma centre in Stoke on Trent,
      UK, as part of the Department of Health Trauma Centre Evaluation Project. A
      historical background to the Evaluation Project is included along with details of
      the evolution of trauma services in North Staffordshire, UK. The authors draw
      upon their personal experiences of working in the pilot centre and provide an
      insight into how the Emergency Department, in particular, met the challenge.

PMID- 8520944
TI  - A late shift in accident and emergency.
AB  - The Accident and Emergency (A & E) department at Harrogate District Hospital in
      North Yorkshire, UK, serves a population of 142,000 in a catchment area that
      covers Harrogate, Knaresborough, Ripon, Nidderdale, part of Wetherby, and
      occasionally Ilkley and Otley. In 1994, 29,884 new patients attended the
      department, and 6760 return visits were made. There are large fluctuations in the
      workload of the department that are difficult to predict. This account of a late
      shift demonstrates particular problems that are associated with a split site
      hospital, the transfer of acutely ill and injured patients to specialised units,
      and how the nursing workforce is depleted by 25% if one nurse is absent due to
      sickness.

PMID- 8520945
TI  - Property and the accident and emergency department.

PMID- 8520946
TI  - Accident and emergency: a student's summary.

PMID- 8520947
TI  - Donway traction splint.

PMID- 8520949
TI  - 3rd International Course on Occupational Hazards and Reproduction. Proceedings.
      Turku, Finland, November 7-11, 1994.

PMID- 8520948
TI  - 'Specialist units'.

PMID- 8520950
TI  - Meta-analyses or collaborative studies.
AB  - In decision making, it is often necessary to select between different strategies,
      and the best decision relies heavily on precise quantitative estimates of risks
      and benefits of the different strategies. To make such estimates, large samples
      are needed, but large studies are very expensive and difficult to conduct,
      especially studies that involve several centers, often in different countries.
      Before such a study is initiated, other options should be fully explored; if data
      already exist, it may be possible to combine results into a single estimate. A
      meta-analysis may be easy to do, but it is difficult to do well; sometimes, a
      meta-analysis may be grossly misleading. Some of the options and pitfalls in
      doing a meta-analysis are revealed in the text. The options for a meta-analysis
      should be considered before a megastudy is launched, and meta-analyses are often
      a useful way of introducing past experience into inference making.

PMID- 8520951
TI  - Validity aspects of exposure and outcome data in reproductive studies.
AB  - Some validity aspects related to various sources on pregnancy outcome and
      exposure are discussed. Register-based data on outcome and exposure are compared
      with workers' own reports. The problems in the use of personal interview data on
      pregnancies are related to the possible selection in recognition and reporting
      the pregnancy outcome. The best way of avoiding misclassification of outcome is
      to resort to medical records whenever possible. Misclassification of exposure is
      most likely a common reason for discrepancies in results in reproductive studies.
      The misclassification of exposure deflates the power of the study to detect the
      true difference between exposed and nonexposed subjects, particularly when the
      prevalence of exposure is low. It is of great importance to confirm, if possible,
      the exposure status by using two or more independent sources of data.

PMID- 8520952
TI  - Effects of parental exposure to solvents on pregnancy outcome.
AB  - The findings and methodological issues of epidemiologic studies on adverse
      developmental effects of parental occupational exposure to organic solvents are
      reviewed. The studies on maternal effects suggest that high exposure to solvents
      may increase the risk of spontaneous abortion, but the findings on congenital
      malformations are inconsistent. Suggestive associations of spontaneous abortions
      have also been observed with some particular solvents. The evidence appears to be
      most adequate for toluene. Evidence on the effects of paternal exposure to
      solvents on pregnancy outcome is limited and inconsistent. Suggestive results
      link paternal exposure to spontaneous abortion, congenital malformation, and low
      birth weight or preterm birth. A common methodological weakness in these studies
      is the inaccurate data on exposure. Positive findings encourage further studies
      with an improved study design and methods, particularly with improved assessment
      of exposure.

PMID- 8520953
TI  - Effects of parental occupational exposure to lead and other metals on spontaneous
      abortion.
AB  - The aim of this article was to summarize the epidemiologic studies on the
      possible impact of parental occupational exposure to lead or other metals on
      spontaneous abortion. For paternal exposure, the total number of abortions in the
      studies with adequate exposure contrast were 340 for lead, 240 for mercury, and
      90 for unspecified metals and, correspondingly, for maternal exposure, about 80
      for lead, 80 for mercury, 70 for nickel, and 130 for exposure to unspecified
      metals. Epidemiologic studies indicate that paternal exposure to lead or mercury
      might be associated with the risk of spontaneous abortion. For maternal exposure,
      no clear conclusion could be reached. In particular, paternal occupational
      exposure levels to metals were substantial compared with population values. Even
      though there are shortcomings in the present knowledge, protective goals for
      paternal exposure to lead and mercury are warranted. More well-designed studies
      on metals are needed.

PMID- 8520954
TI  - Occupation- and exposure-related studies on human sperm.
AB  - Many kinds of exposures and chemicals have been shown to affect human sperm
      quantity and quality. This review focuses first on the best known occupational
      testicular toxin, dibromochloropropane. Prolonged heat is clearly detrimental to
      spermatogenesis. Studies on occupational heat, radiation, and chemical exposures
      and their effects on sperm are reviewed. The evaluation of human sperm studies is
      hampered by inconsistencies in biological analytical methods, in control for
      confounders, and in weaknesses of study design. Still, there is reason to suggest
      that human semen parameters can serve as valuable indicators of toxic and, in
      future, even genotoxic effects of occupational and environmental factors.

PMID- 8520956
TI  - Maternal pesticide exposure and pregnancy outcome.
AB  - Exposure to pesticides is inherent in many agricultural jobs. Most of the
      interest in connection with pesticides and pregnancy outcome has been directed to
      birth defects. Some indications of an elevated risk of limb anomalies have been
      associated with ecologic exposure, maternal environmental exposure to pesticides
      determined by the mother's place of residence, and parental occupation involving
      potential pesticide exposure. Orofacial clefts have been related to maternal
      environmental exposure to pesticides and exposure in agricultural work. Moreover,
      there is evidence that maternal agricultural occupation and pesticide exposure
      may be associated with elevated risk of spontaneous abortion and stillbirth.
      However, some studies have found no indication of reproductive hazards but,
      altogether, the epidemiologic evidence is inconclusive as regards the risk of
      adverse pregnancy outcome.

PMID- 8520955
TI  - Time to pregnancy among women occupationally exposed to lead.
AB  - A retrospective time-to-pregnancy study was conducted among women biologically
      monitored for exposure to lead. The women were participants of a previous study
      on spontaneous abortion. They were classified into exposure categories on the
      basis of questionnaire information, and individual blood lead (B-Pb)
      measurements. The adjusted incidence density ratios (IDR) of clinically
      recognized pregnancies were .93 (95% confidence interval [CI] .56 to 1.57) for
      very low (B-Pb < .5 mumol/L), .84 (CI .48 to 1.45) for low (B-Pb .5 to .9
      mumol/L), and .80 (CI 0.42 to 1.54) for higher (B-Pb > or = 1.0 mumol/L) exposure
      compared with no exposure, in the discrete proportional hazards analysis.
      Exposure to inorganic lead was not associated with fecundability at current, low
      exposure levels. The suggestive finding among the eight most heavily exposed
      women (B-Pb 1.4 to 2.4 mumol/L, IDR .53; CI .19 to 1.52) should be confirmed or
      refuted in a larger study.

PMID- 8520957
TI  - Physical work load and pregnancy outcome.
AB  - Pronounced physical exertion may influence intraabdominal pressure and uterine
      blood flow, hormonal balance, and nutritional status, all of which are important
      determinants of embryonic and fetal development and survival. Most of the
      epidemiologic evidence of reproductive effects from occupational physical
      activity concerns gestational age/premature birth, birth weight/intrauterine
      growth retardation, and spontaneous abortion. Strenuous work, especially when
      involving long hours of standing and walking, seems to increase the risk of
      preterm delivery. The effect on intrauterine growth and spontaneous abortion risk
      is less clear. As a single factor, heavy lifting has in most circumstances not
      been associated with a significantly increased risk of these outcomes. In
      general, heavy work duties should be avoided, and enough rest periods assured,
      especially in late pregnancy.

PMID- 8520958
TI  - Female noise exposure, shift work, and reproduction.
AB  - In addition to having possible direct effects on the fetus, noise induces a
      stress reaction in the mother, possibly causing reproductive disturbances. In
      shift work, many physiological functions and systems that are circadian in nature
      can be disturbed. Study results indicate that occupational noise at the level of
      approximately 85 dB LAeq(8 h) or higher and shift work, especially rotating
      schedules, may have independent negative effects on birth weight and length of
      gestation. Some forms of shift work have also been associated with early fetal
      loss. Moreover, some results have related noise exposure and shift work to
      menstrual disturbance and infertility. Although the evidence is not ample, it is
      prudent to consider exposure to high-level noise and shift work as risks to
      reproduction.

PMID- 8520959
TI  - Magnetic fields of video display terminals and pregnancy outcome.
AB  - The magnetic fields emitted by video display terminals (VDTs) and their potential
      association with pregnancy outcome are discussed. The majority of the
      epidemiologic studies suggest that VDT work is not related to adverse pregnancy
      outcome. The exposure to magnetic fields from modern VDTs is usually even lower
      than that from other sources in the office environment, such as printers and
      photocopying machines. There are, however, some indications of an increased risk
      of adverse pregnancy outcome among women exposed to high levels of extremely low
      frequency magnetic fields of VDTs or electric appliances at home. Because the
      present evidence is not sufficient to allow the drawing of final conclusions, it
      would be important to examine the effects of exposure to higher fields existing
      at industrial work places.

PMID- 8520960
TI  - Reproductive effects of chemical exposures in health professions.
AB  - Numerous chemical substances are handled by persons working in the health care
      sector. At exposure levels that may occur in the occupational setting, some of
      these substances are potentially harmful to the reproductive processes. Among the
      potentially harmful substances are anesthetic gases, antineoplastic agents, and
      sterilants. The epidemiological evidence of increased risks for adverse
      reproductive effects (eg, subfertility, spontaneous abortions, congenital
      defects) from such exposure is not unequivocal. However, due to the toxic
      potential, exposures should be kept at a minimum, and this may be especially
      important for workers who are pregnant or are planning to achieve pregnancy.

PMID- 8520961
TI  - Biological agents and pregnancy.
AB  - Pregnant women are exposed to many biological, eg microbial, agents, which are
      potentially harmful to the fetus. The reported rates of vertical transmission of
      hepatitis B and human immunodeficiency virus vary between 3 to 90% and 0 to 65%,
      respectively. The susceptibility to hepatitis B and human immunodeficiency
      infection is increased in pregnant physicians, midwives, and nurses because of
      the bloodborne nature of these viruses. Also, TORCH (toxoplasmosis-rubella
      cytomegalovirus-herpes) infections, acquired during pregnancy, may result in
      congenital infection, and serious sequelae in the neonatal period or years after
      birth. Schoolteachers and daycare personnel have an increased risk of perinatal
      varicella, "fifth disease," and mumps. Perinatal listeriosis affects one in
      20,000 births and may result in fetal wastage. Because of the risk of the
      possibility of vertical transmission, immunization during pregnancy with live
      virus vaccines is not recommended.

PMID- 8520962
TI  - The European Community Directive on the classification and labeling of chemicals
      for reproductive toxicity.
AB  - The classification and labeling of dangerous substances was first introduced in
      1967 in the European Community with Council Directive 67/548/EEC, known as the
      Dangerous Substances Directive. The Sixth Amendment to this directive in 1979
      introduced a notification procedure for new chemicals and a requirement for
      labeling chemicals for toxicity. Three special categories for labeling were for
      carcinogenicity, mutagenicity, and teratogenicity. The teratogenicity
      classification was restricted to chemicals inducing teratogenic effects in the
      classical sense of the word, ie, producing only gross structural malformations.
      Discussions by expert advisors to the European Commission over several years led
      to a widening of concern in this area of toxicology and, under the recent Seventh
      Amendment, the classification of "teratology" has been changed to "toxic to
      reproduction." This includes adverse effects on fertility, pre- and postnatal
      development, and lactation, and encompasses not only structural but also
      functional deficits. This will bring about a major change in the testing
      requirements to allow adequate classification of chemicals for these other
      aspects of reproductive toxicity.

PMID- 8520963
TI  - Nordic criteria for reproductive toxicity.
AB  - Scientific criteria for assessment of the reproductive toxicity of chemicals have
      been proposed by a Nordic group of experts and regulatory representatives. The
      criteria take into account the results of clinical studies as well as of
      experimental research. The criteria should be useful in, for example, product
      control and labeling and planning of a safe work environment. The proposed Nordic
      criteria and examples of the assessment of the reproductive toxicity of some
      chemicals are presented.

PMID- 8520964
TI  - Experiences in developing legislation protecting reproductive health.
AB  - The law regarding special maternity leave for pregnant women in hazardous work
      situations has been in effect since 1981 in Denmark. In Finland, legislation
      regarding the protection of the reproductive health of working men and women and
      of pregnant women has been in effect since 1991. According to the special
      maternity leave law, women who are exposed to certain chemical, physical, or
      biological agents that are considered to be harmful to the fetus may be entitled
      to special maternity leave and benefits. In Denmark and in Finland, approximately
      1% and 0.1%, respectively, of pregnant women have used the special maternity
      leave due to a risky work situation. In Finland, the yearly costs of the leave
      have been US $200,000 to $250,000. Trained occupational physicians can facilitate
      changes at the workplace that will decrease the need for special maternity leave.

PMID- 8520965
TI  - The molecular genetics of human sex determination.
AB  - The classical conception of the chromosomal mechanism of sex determination
      presumes a chromosome unique for and determining the heterogametic sex. On the
      basis of recent evidence, however, this picture is becoming increasingly complex,
      with a multitude of genes appearing to interact simultaneously or successively to
      bring about the gonadal phenotype. The genes identified so far that are thought
      to be involved in the process of human sex determination are distributed on
      various chromosomes, but the consecution of their function remains to be
      elucidated. To the Y chromosome only a relative role can be ascribed, and it has
      not yet been established which gene is on top of the cascade. All of the genes
      under discussion are involved in transcriptional control, and at least the
      majority of them appear to exert pleiotropic effects. The regulation of their
      expression must still be defined, and it will be a long way before a link to
      gonadal morphogenesis is ultimately found.

PMID- 8520966
TI  - Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic
      prospects.
AB  - This review of angiogenesis aims to describe (a) stimuli that either elicit or
      antagonize angiogenesis, (b) the response of the vasculature to angiogenic or
      anti-angiogenic stimuli, i.e., processes required for the formation of new
      vessels, (c) aspects of angiogenesis relating to tissue remodeling and disease,
      and (d) the potential of angiogenic or antiangiogenic therapeutic measures.
      Angiogenesis, the formation of new vessels from existing microvessels, is
      important in embryogenesis, wound healing, diabetic retinopathy, tumor growth,
      and other diseases. Hypoxia and other as yet ill-defined stimuli drive tumor,
      inflammatory, and connective tissue cells to generate angiogenic molecules such
      as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF),
      transforming growth factor-beta (TGF-beta), platelet-derived growth factor
      (PDGF), and others. Natural and synthetic angiogenesis inhibitors such as
      angiostatin and thalidomide can repress angiogenesis. Angiogenic and
      antiangiogenic molecules control the formation of new vessels via different
      mechanisms. VEGF and FGF elicit their effects mainly via direct action on
      relevant endothelial cells. TGF-beta and PDGF can attract inflammatory or
      connective tissue cells which in turn control angiogenesis. Additionally, PDGF
      may act differently on specific phenotypes of endothelial cells that are engaged
      in angiogenesis or that are of microvascular origin. Thus phenotypic traits of
      endothelial cells committed to angiogenesis may determine their cellular
      responses to given stimuli. Processes necessary for new vessel formation and
      regulated by angiogenic/antiangiogenic molecules include the migration and
      proliferation of endothelial cells from the microvasculature, the controlled
      expression of proteolytic enzymes, the breakdown and reassembly of extracellular
      matrix, and the morphogenic process of endothelial tube formation. In animal
      models some angiogenesis-dependent diseases can be controlled via induction or
      inhibition of new vessel formation. Life-threatening infantile hemangiomas are a
      first established indication for antiangiogenic therapy in humans. Treatment of
      other diseases by modulation of angiogenesis are currently tested in clinical
      trials. Thus the manipulation of new vessel formation in angiogenesis-dependent
      conditions such as wound healing, inflammatory diseases, ischemic heart and
      peripheral vascular disease, myocardial infarction, diabetic retinopathy, and
      cancer is likely to create new therapeutic options.

PMID- 8520967
TI  - Molecular analysis of the physiological and pathophysiological role of alpha 4
      integrins.

PMID- 8520969
TI  - Relationship of high-density lipoprotein subfractions and cholesteryl ester
      transfer protein in plasma to carotid artery wall thickness.
AB  - High plasma concentrations of high-density lipoprotein (HDL) cholesterol are a
      powerful indicator of low vascular risk. By decreasing HDL cholesterol,
      cholesteryl ester transfer protein (CETP) could perhaps constitute an atherogenic
      protein. We measured HDL cholesterol and HDL subfractions and quantified CETP
      mass in fasting plasma in 21 asymptomatic probands, and related these variables
      to the mean intima media thickness of the extracranial carotid arteries. HDL2
      cholesterol, the less dense HDL subfraction, was inversely related to carotid
      wall thickness (r = -0.378; P < 0.05), and CETP was directly related to carotid
      wall thickness (r = 0.436; P < 0.05). In plasma CETP is associated mostly with
      the HDL3 subfraction. We therefore calculated from our measurements the relative
      CETP content of HDL3, i.e., CETP/HDL3 cholesterol. This ratio was correlated with
      carotid wall thickness stronger than any other variable measured (r = 0.718, P <
      0.001). We conclude that variation in HDL subfractions and CETP may be more
      closely associated with carotid intima media thickness than the accepted strong
      risk factor of HDL cholesterol.

PMID- 8520970
TI  - Electrophoretic screening for human apolipoprotein C-II variants: repeated
      identification of apolipoprotein C-II(K19T).
AB  - Screening for apolipoprotein (apo) C-II variants in the plasma of 400 students,
      600 patients of a cardiological rehabilitation center, and 1200 patients of an
      outpatient lipid clinic by isoelectric focusing and subsequent anti-apo C-II
      immunoblotting led to the identification of four individuals whose plasma samples
      contained an apo C-II isoform with an abnormal isoelectric point. In all cases
      direct sequencing of PCR-amplified DNA assessed a heterozygous A to C
      transversion in codon 19 of the apo C-II gene which leads to the replacement of
      lysine with threonine. Two of the four index patients presented with moderate
      hypertriglyceridemia; one suffered from severe hyperlipidemia, with triglyceride
      levels ranging between 180 and 1900 mg/dl, depending on dietary changes.
      Sequencing of this proband's lipoprotein lipase gene showed no alteration
      compared to the wild-type sequence. A study in his family revealed that
      heterozygosity for apo C-II(K19T) is not associated with differences in mean
      lipid and lipoprotein concentrations. In conclusion, apo C-II(K19T) occurs in
      Germany at a frequency of approximately 1 in 550. Although this variant is not
      sufficient to cause hypertriglyceridemia, it may be possible that apo C-II(K19T)
      cause hypertriglyceridemia in the presence of additional as yet unidentified
      environmental and/or genetic factors.

PMID- 8520968
TI  - Molecular biology of testicular germ cell tumors: current status.

PMID- 8520971
TI  - Effect of cyclosporin analogues on histamine release from rat peritoneal mast
      cells and rat basophilic leukaemia cells.

PMID- 8520972
TI  - Antibiotics change contractility of guinea pig aorta and trachea to histamine
      after a short exposure to LPS.

PMID- 8520973
TI  - Relaxin enhances the coronary outflow in perfused guinea-pig heart: correlation
      with histamine and nitric oxide.

PMID- 8520974
TI  - Helicobacter pylori, oxygen-derived free radicals and histamine in peptic ulcer
      and inflammatory disease.

PMID- 8520975
TI  - Stimulation of gastric acid secretion by (R)-alpha-methylhistamine in the rat:
      influence of the increased gastric juice volume on ethanol-induced lesions.

PMID- 8520976
TI  - Different activities of impromidine and related phenyl-(pyridylalkyl)guanidines
      at cardiac and gastric H2 receptors.

PMID- 8520977
TI  - Relaxin inhibits histamine release from mast cells: involvement of nitric oxide
      production.

PMID- 8520978
TI  - The H1-histamine receptor antagonist dithiaden inhibits stimulated platelet
      aggregation, malondialdehyde formation and thromboxane production in vitro.

PMID- 8520979
TI  - Storage and release of histamine in human platelets.

PMID- 8520980
TI  - Time-course of the histamine release from human peripheral blood monocytes and
      the influence of ketotifen and disodium cromoglycate (DSCG).

PMID- 8520981
TI  - Histamine mobilizes intracellular Ca(2+)-pools sensitive to thapsigargin in
      cultured guinea-pig tracheal smooth muscle cells.

PMID- 8520982
TI  - Immunologic and non-immunologic release of histamine and tryptase from human
      heart mast cells.

PMID- 8520983
TI  - In vitro study of endothelium-dependent histamine release from canine mesenteric
      arterial segments.

PMID- 8520984
TI  - Role of G-proteins in peptidergic activation of both human and rat cutaneous mast
      cells.

PMID- 8520985
TI  - Contribution of serotonin reuptake to differential histamine and serotonin
      secretion from rat peritoneal mast cells.

PMID- 8520986
TI  - Enhanced human basophil activation and histamine release by IL3 priming:
      application to sulfite allergy diagnosis.

PMID- 8520987
TI  - Effects of acrivastine, azelastine, cetirizine and noberastine on rat peritoneal
      mast cells.

PMID- 8520988
TI  - Ouabain-insensitive 86Rb+ transport in peritoneal mast cells: role in histamine
      release.

PMID- 8520989
TI  - Microorganisms and mediator release: a mechanism in respiratory disorders caused
      by infectious and environmental exposure.

PMID- 8520990
TI  - Effect of the H1-antagonist bromadryl on mast cells in pregnant rats ex vivo.

PMID- 8520991
TI  - Effect of pheniramine, chlorpheniramine and brompheniramine on stimulated blood
      platelets: structure-activity relationships.

PMID- 8520992
TI  - Role of stress in histamine-morphine interactions.

PMID- 8520993
TI  - The corticosterone response to cholinergic and CRF receptor stimulation in rats
      exposed to social crowding stress.

PMID- 8520994
TI  - Role of histamine in spinal cord evoked potentials and edema following spinal
      cord injury: experimental observations in the rat.

PMID- 8520995
TI  - Histamine-sensitive 86Rb transport in cultured type-2 astrocytes of rat brain.

PMID- 8520996
TI  - Effect of histamine on corticosteroid secretion of isolated human and rat
      adrenocortical cells.

PMID- 8520997
TI  - Effects of type I and type II phospholipase A2 on rat peritoneal mast cells.

PMID- 8520998
TI  - Degranulation and decrease in histamine levels of thalamic mast cells coincides
      with corticosterone secretion induced by compound 48/80.

PMID- 8520999
TI  - Portocaval shunt, an H3-antagonist and plasma hormone levels.

PMID- 8521000
TI  - Long-term effects of portocaval anastomosis in rats on brain levels of histamine
      and methylhistamine.

PMID- 8521001
TI  - Histamine induces a selective albumin permeation through the blood-brain barrier
      in vitro.

PMID- 8521002
TI  - Characterization of muscarinic acetylcholine heteroreceptors modulating in vivo
      release of histamine in the rat hypothalamus.

PMID- 8521003
TI  - Involvement of central histaminergic mechanisms and prostaglandins in carbachol
      induced corticosterone secretion.

PMID- 8521004
TI  - Stress and brain H3-histamine receptors.

PMID- 8521005
TI  - Reinforcement effect of histamine on the differentiation of murine myeloblasts
      and promyelocytes induced by granulocyte colony stimulating factor.

PMID- 8521006
TI  - Influence of proliferative stimulation on the activity of rat intestinal diamine
      oxidase.

PMID- 8521007
TI  - Histamine receptors in human mammary gland, different benign lesions and mammary
      carcinomas.

PMID- 8521008
TI  - Lack of inhibition by cyclosporin in the Schultz-Dale reaction.

PMID- 8521009
TI  - Expression of histamine receptors in different cell lines derived from mammary
      gland and human breast carcinomas.

PMID- 8521010
TI  - H1 and H2 histamine receptors in histiocytic lymphoma cell line U-937.

PMID- 8521011
TI  - Rat fetal and postnatal development after treatment in utero with histamine H1
      antagonists.

PMID- 8521012
TI  - Histamine-induced differentiation of eosinophilic subclone of HL-60 cells.

PMID- 8521013
TI  - Modification of cardiovascular response and histamine release by prophylactic
      antibiotic drugs in complicated surgery: a prospective randomized trial in a pig
      experimental model.

PMID- 8521014
TI  - Histamine response to various stimuli during CABG-surgery: a study in patients
      with and without prophylactically administered H1- and H2-receptor antagonists.

PMID- 8521015
TI  - Model building strategies for risk analysis of perioperative histamine-related
      cardiorespiratory disturbances.

PMID- 8521016
TI  - Pruritus and mast cell proliferation in the skin of haemodialysis patients.

PMID- 8521017
TI  - Histamine content in lymph nodes from patients with malignant lymphomas.

PMID- 8521018
TI  - Increased plasma tele-methylhistamine levels in the rat: effects on plasma and
      tissue histamine and its elimination.

PMID- 8521019
TI  - A steric approach for the design of antihistamines with low muscarinic receptor
      antagonism.

PMID- 8521020
TI  - Receptor subtypes involved in the modulatory action of histamine on the
      contractility of the rat vas deferens.

PMID- 8521021
TI  - Determination of the activity of diamine oxidase in extremely small tissue
      samples.

PMID- 8521022
TI  - Histamine-induced activation of ventricular ectopic pacemakers and contractile
      myocardium: role of histamine receptors.

PMID- 8521023
TI  - Electrophysiological effects of azelastine in isolated guinea pig atrial and
      ventricular fibers.

PMID- 8521024
TI  - Antimicrobial resistance in Streptococcus pneumoniae: can immunization prevent
      its spread?

PMID- 8521025
TI  - Consequences of pancreas transplantation.
AB  - PKT has become an important option in selected IDDM patients being considered for
      kidney transplantation because of its ability to offer superior glycemic control
      and improved quality of life. As both kidney graft survival and overall mortality
      are comparable following PKT and kidney transplantation alone at many centers,
      neither the survival of the patient nor the success of the kidney transplant need
      be jeopardized by the addition of a pancreas graft. The greater morbidity of PKT
      can be justified by the evidence that a pancreas graft will prevent recurrent
      diabetic nephropathy, result in greater improvements in sensory/motor neuropathy,
      and in some but not all studies, cause greater stabilization of eye disease.
      Improvements in lipid profiles observed after PKT but not after kidney transplant
      alone may predict better cardiovascular outcomes as well. Determination of who
      should receive an isolated pancreas transplant is more complex. Success rates are
      lower than after PKT. It remains important to ascertain that the candidate is
      susceptible to diabetic complications, or has repeated bouts of hypoglycemia or
      ketoacidosis unresponsive to other measures to justify the risks of long-term
      immuno-suppression. More difficult to determine is whether or when individuals
      who have advancing diabetic complications yet relatively preserved renal function
      (creatinine clearance > 70 mL/min) should become candidates. For now, each
      individual is considered on a case by case basis and the relative risks and
      benefits for each individual are carefully assessed. However, patient selection
      will be greatly aided by further research assessing the long-term risks and
      benefits of all types of pancreas transplantation. Pancreas transplantation will
      remain an important option in the treatment of IDDM until alternative strategies
      are developed that can provide equal glycemic control with less or no
      immunosuppression or less overall morbidity. Most of the research to date has
      concentrated on the consequences of pancreas transplantation on microvascular
      complications. However, cardiovascular disease events represent the greatest
      cause of mortality in pancreas transplant candidates. Thus, changes in
      cardiovascular risk after pancreas transplantation may be more important to long
      term survival than any other factor and should receive greater attention in
      future studies.

PMID- 8521026
TI  - The cell biology of reperfusion injury in the kidney.

PMID- 8521027
TI  - Acute lung injury: the role of cytokines in the elicitation of neutrophils.
AB  - Cytokine networks between immune and nonimmune cells of the alveolar-capillary
      membrane are necessary for cellular communication during pulmonary inflammation.
      The subsequent events of these cellular/humoral interactions are pivotal to the
      initiation and propagation of the inflammatory response leading to pulmonary
      injury. The studies cited in this paper underscore the interrelationship of early
      response cytokines, adhesion molecules, and the chemokine IL-8 that orchestrate
      the recruitment of neutrophils into the lung. The paradigm for neutrophil
      extravasation is likely operative in the microvasculature of the lung, and
      consists of four or more steps (Figure 3). First, acute lung injury results in
      the activation of microvascular endothelium in response to the local generation
      of TNF or IL-1, leading to expression of endothelial cell-derived E- and P
      selectins and ICAM-1. The constitutive presence of neutrophil-derived L-selectin
      allows for the initial adhesive interaction of neutrophils with endothelial cell
      selectins leading to the "rolling" effect. Second, generation of IL-8 leads to
      the activation of neutrophils in the vascular compartment and expression of beta
      2 integrins, while L-selectin is concomitantly shed. Third, the interaction of
      the neutrophil beta 2 integrin with its receptor/ligand, ICAM-1, results in the
      rapid arrest of neutrophils on the endothelium. Fourth, the subsequent events
      leading to neutrophil extravasation beyond the vascular compartment are dependent
      upon a combination of haplotaxis (migration in response to an insoluble
      gradient), the continued expression of beta 2 integrins on neutrophils and ICAM-1
      on nonimmune cells, and the maintenance of a neutrophil specific (IL-8)
      chemotactic gradient. The participation of IL-8 and potentially other C-X-C
      chemokines in the inflammatory response appears to be critical for the
      orchestration of the directed migration of inflammatory leukocytes into the lung.
      After arriving in the lung, these activated leukocytes can respond to noxious
      stimuli or induce pulmonary injury through the release of reactive oxygen
      metabolites, proteolytic enzymes, and additional cytokines. Our current knowledge
      and future investigations regarding the mechanisms involved in neutrophil
      elicitation may allow us to employ clinical interventional strategies that will
      attenuate neutrophil-dependent acute lung injury, such as ARDS.

PMID- 8521028
TI  - Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft
      rejection.
AB  - BACKGROUND: Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1)
      lymphocytes mediating both cellular immunity and alloantibody production. Th-1
      lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production,
      suggesting that increased IgG2 production might occur during AR. The purpose of
      this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios
      might correlate with AR. METHODS: Eighteen recipients of lung allografts
      underwent a total of 25 bronchoscopies for surveillance or at times of suspected
      infection or AR. Bronchoalveolar lavage (BAL), serum collection, and
      transbronchial biopsy (TB) were performed on all patients. gamma IFN, IgG1, IgG2
      levels, and the ratio of IgG2/IgG1 were determined in serum and BAL and matched
      with TB histology. Five nonsmoking normal volunteers undergoing bronchoscopy,
      BAL, and serum collection served as controls. RESULTS: IgG2 was upregulated in
      allograft BAL during AR as determined by the ratio IgG2/IgG1 (2.91 +/- 0.79 SEM
      vs 0.62 +/- SEM, p < 0.019, IgG2/IgG1, AR BAL vs non-AR BAL, respectively). An
      IgG2/IgG1 > or = 1 in allograft BAL (95% confidence intervals 1.26 to 4.56) was
      80% specific and 91% sensitive for the diagnosis of AR with a positive predictive
      value of 92%. A BAL IgG2/IgG1 < 1 (95% confidence interval 0.27 to 0.97) had a
      negative predictive value of 77%. After therapy in two patients the elevated
      IgG2/IgG1 ratio reversed to normal (ie, < 1) with histologic resolution of AR.
      CONCLUSIONS: Human lung AR is associated with a locally increased IgG2/IgG1 ratio
      suggesting locally upregulated Th-1 lymphocyte activity during lung AR.

PMID- 8521029
TI  - Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA
      expression during experimental liver injury: implications for treatment of
      hepatic fibrosis.
AB  - BACKGROUND: A central feature of liver injury involves activation of hepatic
      lipocytes (perisinusoidal cells), a process characterized by their morphologic
      transformation to myofibroblast-like cells. Important features of this process
      include new expression of smooth muscle alpha actin and production of increased
      amounts of extracellular matrix. Interferon gamma is a cytokine with
      immunomodulatory and antifibrotic properties that has potent effects on lipocytes
      in a culture model of activation. The aim of this study was to determine if
      interferon gamma inhibited lipocyte activation in an in vivo model of liver
      injury and whether this effect resulted in an overall reduction in hepatic
      fibrosis. METHODS: Liver injury (with ensuing fibrosis) was induced by carbon
      tetrachloride. Interferon gamma was infused continuously by osmotic pump during
      the induction of liver fibrosis, after which lipocytes were isolated and features
      of lipocyte activation were examined. Finally, whole liver type I collagen mRNA
      was quantitated. RESULTS: Carbon tetrachloride caused histological fibrosis,
      which was significantly reduced on a quantitative basis by interferon gamma.
      Immunocytochemical analysis of livers from animals treated with interferon gamma
      demonstrated a significant reduction in the number of desmin positive cells
      (lipocytes) in portal and noncentral lobular areas as well as in bands of
      fibrosis, consistent with reduced lipocyte proliferation. Using discontinuous
      density centrifugation, two populations of lipocytes were isolated and
      characterized: one migrating in the upper layer of the gradient and another to
      the lower layer. Interferon gamma markedly reduced smooth muscle alpha actin
      expression (by immunoblot) in upper layer lipocytes and had significant
      inhibitory but less dramatic effects on lower layer lipocytes. Interferon gamma
      also reduced collagen I mRNA to 36% (p < 0.001, interferon gamma versus control)
      and 46% (p < 0.01) of control values in upper and lower layer lipocyte samples,
      respectively. Effects of interferon gamma on expression of cellular fibronectin
      mRNA were similar. Smooth muscle actin as well as type I collagen and cellular
      fibronectin mRNA were more abundant in lower than upper layer lipocytes in both
      control and interferon gamma treated animals. Finally, interferon gamma reduced
      collagen I mRNA in whole liver specimens to 36% of control values (p < 0.005, for
      interferon gamma compared to control, n = 6). CONCLUSIONS: The data indicate that
      interferon gamma inhibits lipocyte activation and extracellular matrix production
      in vivo during liver injury, which results in an overall decrease in hepatic
      fibrosis. Further, the data demonstrate heterogeneity in lipocytes during
      activation and identify a novel population of markedly activated lipocytes.

PMID- 8521030
TI  - The limits of the possible: models of power supply and demand in cycling.
AB  - This paper outlines a general strategy for mathematical modeling of cycling
      performance. This strategy involves formulating one expression describing the
      power available for external work from physiological sources. The variables used
      in this expression include maximal aerobic power (VO2max), fractional utilisation
      of VO2max, mechanical efficiency, maximal accumulated oxygen deficit, and the
      time constants relating to the expression of aerobic and anaerobic capacities. A
      second expression describing the power demand of cycling is then constructed. The
      variables used in this expression include the mass, projected frontal area and
      drag characteristics of the system, the coefficient of rolling resistance,
      environmental variables such as temperature, barometric pressure, relative
      humidity, wind speed and direction and the slope of the course. The two
      expressions are equated and solved using an iterative procedure. Two series of
      trials were used to assess the predictive accuracy of the model, one using track
      endurance performances and the other a 26 km road time-trial. The correlations
      between actual and predicted times have been excellent (0.92-0.95, p < or =
      0.0001), with small mean differences (0-1.83% of mean performance time) and mean
      absolute differences (1.07-3.24%). The model allows us to make predictions about
      the effect of equipment changes and environmental factors, to compare
      performances under very different conditions, and to predict the limits of the
      possible in cycling performance. A range of options designed to improve cycling
      performance is described.

PMID- 8521031
TI  - Children's readiness for learning front crawl swimming.
AB  - This study attempted to establish whether an optimal age could be identified at
      which children were ready to learn the front crawl swimming stroke. The variables
      examined were: the number of lessons, the age of commencing lessons and the time
      duration for learning to swim 10m front crawl (Level 3). Longitudinal records of
      326 children, aged between 2 and 8 years, were analysed using General Linear
      Model two-way (Age x Sex) analysis of variance procedures. The main effect for
      age was significant (p < 0.001) for all three variables. Post hoc analysis
      revealed that the children who started at 5 years of age received significantly
      fewer number of lessons and took shorter duration compared to those who commenced
      learning to swim at an earlier age. Whether pupils started lessons at 2, 3 or 4
      years of age, they achieved Level 3 at approximately the same mean age of 5 1/2
      years. The optimal readiness period was identified in this study to be between 5
      and 6 years of age. There was little evidence of gender differences for all three
      variables.

PMID- 8521032
TI  - Injury data collection in the rugby codes.
AB  - A large number of studies into injuries in rugby union and league have been
      conducted. This review analysed published reports on rugby injuries in relation
      to their methodological rigour. Desirable criteria for sports injury data
      collection were identified from the literature. Each study was then analysed in
      respect to the criteria. Results indicated that no studies met all of the
      desirable criteria. Recommendations for sports injury methodological design are
      given.

PMID- 8521033
TI  - The etiology of paddler's shoulder.
AB  - Training methods used in competitive flatwater paddling often lead to a common
      pattern of soft tissue injuries that affect the upper limb. Of particular
      frequency is paddler's shoulder, a condition that can become chronic and may
      result in permanent damage. The authors suggest that the cumulative effect of
      poorly structured resistance training initiates the deteriorative process and
      together with the repetitiveness of on-water training results in the pathologies
      referred to as paddler's shoulder.

PMID- 8521034
TI  - Evaluation of mass spectrometric techniques for characterization of engineered
      proteins.
AB  - Mass spectrometric characterization of engineered proteins has been examined
      using bovine recombinant Acyl-CoA-Binding Protein (rACBP), [15N]-labeled rACBP,
      and a number of sequence variants of ACBP produced by site-directed mutagenesis.
      The mass spectrometric techniques include ESIMS and MALDIMS for analysis of the
      intact protein. Peptide maps have been obtained either by direct analysis of
      enzymatically derived mixtures by PDMS, ESIMS, and MALDIMS or by off- and on-line
      HPLC-mass spectrometry. ESIMS was found to be most accurate for analysis of
      intact proteins. The best sequence coverage in mapping was obtained by LC-ESIMS
      and by direct mixture analysis by MALDIMS. The latter technique was favorable in
      terms of sensitivity and speed. A general strategy for mass spectrometric
      characterization of engineered proteins is suggested.

PMID- 8521035
TI  - A new method of bipolymerase sequencing prevents "stop-bands".
AB  - This article presents a relatively quick and cost-effective DNA sequencing method
      that prevents the formation of stop-bands. This method uses a combination of Taq
      and Sequenase that allows sequencing at both low and high temperatures. The
      ability to sequence at a high temperature appears to be the fundamental component
      in preventing stop-band formation in G+C rich regions.

PMID- 8521036
TI  - Precise large deletions by the PCR-based overlap extension method.
AB  - The authors describe an efficient method for generating large deletions (> 200
      nts) of precise length using the PCR-based method of gene splicing by overlap
      extension (1). This method is technically simple and less time consuming than
      conventional loop-out mutagenesis techniques requiring preparation of a single
      stranded DNA template.

PMID- 8521037
TI  - Ultrafast protein determinations using microwave enhancement.
AB  - We present here microwave-based modifications of standard protein assays that
      dramatically reduce the time required to determine protein concentrations.
      Typical protein determinations involve incubation times ranging from 15-60 min.
      Microwave irradiation of specimens reduces this time requirement to 10-20 s
      without compromising accuracy or reliability. The remarkable speed with which
      protein determinations may be carried out using microwave enhancement greatly
      simplifies general laboratory procedures that depend on the estimation of protein
      concentrations.

PMID- 8521038
TI  - Preparation, manipulation, and pulse strategy for one-dimensional pulsed-field
      gel electrophoresis (ODPFGE).
AB  - The underlying principles for zero-integrated-field electrophoresis (ZIFE) pulses
      and more general forward-biased pulse schemes are reviewed for one-dimensional
      pulsed-field gel electrophoresis (ODPFGE) separations of large DNA molecules.
      Detailed descriptions of materials, preparation protocols, hardware requirements,
      and procedures are given. A variety of gel pictures for known yeast DNA markers
      are shown.

PMID- 8521039
TI  - Epitope mapping of recombinant antigens by transposon mutagenesis.
AB  - We describe a method for generating a plasmid library expressing random
      truncations of a recombinant protein and for epitope mapping by screening the
      library with monoclonal antibodies. The key step is the random introduction of
      the transposon, Tn1000, which carries stop codons in all three reading frames,
      into a bacterial expression plasmid by using a simple bacterial mating procedure.
      Antibody-positive clones are then selected and the point of protein truncation is
      determined by sequencing the plasmid DNA at the point of transposon insertion.
      One advantage of the method is that no subcloning or in vitro manipulation of DNA
      is necessary.

PMID- 8521040
TI  - Bacillus thuringiensis growth and toxicity. Basic and applied considerations.
AB  - Despite the known importance of the composition of culture media and culture
      conditions on Bacillus thuringiensis growth and toxicity, very few reviews are
      concerned with this subject. This article reviews some aspects of the
      microbiology of Bacillus thuringiensis, and how toxicity is affected by the
      composition of growth media and bioreactor operation.

PMID- 8521041
TI  - Synthetic peptides in biochemical research.
AB  - Synthetic peptides play an important role in many areas of biological research.
      Advances in synthetic chemistry and automation over the past few years have
      resulted in increasingly reliable and rapid syntheses. As a result, peptides are
      now frequently employed in immunological studies, structural studies, as enzyme
      substrates, in ligand/receptor studies, and as probes for a range of molecular
      interactions. This review describes solid-phase peptide synthesis and the
      applications of synthetic peptides in molecular biology and biochemistry.

PMID- 8521042
TI  - HSV as a gene transfer vector for the nervous system.
AB  - Gene therapy for diseases of the nervous system requires vectors capable of
      delivering the therapeutic gene into postmitotic cells in vivo. Herpes simplex
      virus type 1 is a neurotropic virus that naturally establishes latency in neurons
      of the peripheral nervous system. Replication defective HSV vectors have been
      developed; these are deleted for at least one essential immediate early
      regulatory gene, rendering the virus less cytotoxic, incapable of reactivation,
      but still capable of establishing latency. Foreign genes can be vigorously
      expressed from an HSV-based vector in a transient manner in brain and other
      tissues. Long-term but weak foreign gene expression may be achieved in the
      nervous system by exploiting the transcriptional control mechanisms of the
      natural viral latency active promoter. To meet the needs of specific
      applications, either highly active long-term or regulatable transgene expression
      will be needed, requiring further studies in order to design the appropriate
      latency-based promoter systems.

PMID- 8521043
TI  - Issues in incorporation semantic integrity in molecular biological object
      oriented databases.
AB  - Issues critical to ensuring semantic integrity in molecular biological data
      collections have been identified and include complexity, exceptions, missing
      data, changing models, holism and integration, delocalized data, interoperability
      and nomenclature. This combination is peculiar to biology and presents some
      interesting problems as a result. Little is known about semantic checking in
      object-oriented databases in general, but because such technology appears highly
      suitable for modeling biological data, it is appropriate to examine the ways in
      which object-oriented technology can support this functionality. It is concluded
      that object-oriented technology will support semantic checking even in a complex
      domain like biology. We propose 10 guidelines for future work including ways of
      treating exceptional cases and 'positioning' of constraints in a schema.

PMID- 8521044
TI  - A new algorithm for predicting splice site sequence based on an improvement of
      categorical discriminant analysis.
AB  - The splicing signals which govern the excision of introns are not yet well
      explained, since actual splice site sequences are to some extent different from
      the generally accepted consensus sequences. While a quantification method
      (categorical discriminant analysis: CDA) has been proposed to analyze splice site
      signals, sample sequences lying in the overlapping region of sample scores are
      not discriminated well by CDA, thus limiting the predictive ability of this
      analytical technique. In this paper, we propose a method to improve the
      performance of CDA, which is applicable to the analysis of 5'-splice site signals
      in various mammalian genes. The proposed algorithm has revealed a distinct
      enhancement in the predicting ability compared to that of traditional CDA and
      could explain point mutations in the 5'-splice site region of rabbit beta-globin
      gene fairly well.

PMID- 8521045
TI  - WIMOVAC: a software package for modelling the dynamics of plant leaf and canopy
      photosynthesis.
AB  - The ability to predict net carbon exchange and production of vegetation in
      response to predicted atmospheric and climate change is critical to assessing the
      potential impacts of these changes. Mathematical models provide an important tool
      in the study of whole plant, canopy and ecosystem responses to global
      environmental change. Because this requires prediction beyond experience,
      mechanistic rather than empirical models are needed. The uniformity and strong
      understanding of the photosynthetic process, which is the primary point of
      response of plant production to global atmospheric change, provides a basis for
      such an approach. Existing modelling systems have been developed primarily for
      expert modellers and have not been easily accessible to experimentalists,
      managers and students. Here we describe a modular modelling system operating
      within Windows to provide this access. WIMOVAC (Windows Intuitive Model of
      Vegetation response to Atmosphere and Climate Change) is designed to facilitate
      the modelling of various aspects of plant photosynthesis with particular emphasis
      on the effects of global climate change. WIMOVAC has been designed to run on IBM
      PC-compatible computers running Microsoft Windows. The package allows the
      sophisticated control of the simulation processes for photosynthesis through a
      standardized Windows user interface and provides automatically formatted results
      as either tabulated data or as a range of customizable graphs. WIMOVAC has been
      written in Microsoft Visual Basic, to facilitate the rapid development of user
      friendly modules within the familiar Windows framework, while allowing a
      structured development. The highly interactive nature of controls adopted by
      WIMOVAC makes it suitable for research, management and educational purposes.

PMID- 8521046
TI  - Three-dimensional reconstruction of helical structures with fast inversion of
      very large Fourier transforms.
AB  - A single projection of a helical distribution of matter allows one to obtain the
      complete three-dimensional reconstruction of the structure. This task is usually
      performed by a Fourier-Bessel algorithm, which is more efficient than a customary
      fast Fourier transform inversion. This article describes how to achieve such a
      result by a direct Fourier method in a reasonable time. Once the two-dimensional
      transform of the projection is obtained from the source image, it is possible to
      build up the three-dimensional transform array, in Cartesian coordinates, that
      yields the reconstruction by a straightforward Fourier inversion. Images of
      projected helices should be studied with high sampling rates to enhance the
      resolution, and the segments of helix should be long enough to give a
      satisfactory signal-to-noise ratio. These conditions result in three-dimensional
      transform arrays that would require one or more gigabytes of storage. The
      strategy proposed here requires much less storage and is fast enough to allow the
      reconstruction to be performed with different parameters and filters in a very
      short time without any sacrifice in resolution.

PMID- 8521047
TI  - Identification of common motifs in unaligned DNA sequences: application to
      Escherichia coli Lrp regulon.
AB  - We describe a relatively simple method for the identification of common motifs in
      DNA sequences that are known to share a common function. The input sequences are
      unaligned and there is no information regarding the position or orientation of
      the motif. Often such data exists for protein-binding regions, where genetic or
      molecular information that defines the binding region is available, but the
      specific recognition site within it is unknown. The method is based on the
      principle of 'divide and conquer'; we first search for dominant submotifs and
      then build full-length motifs around them. This method has several useful
      features: (i) it screens all submotifs so that the results are independent of the
      sequence order in the data; (ii) it allows the submotifs to contain spacers;
      (iii) it identifies an existing motif even if the data contains 'noise'; (iv) its
      running time depends linearly on the total length of the input. The method is
      demonstrated on two groups of protein-binding sequences: a well-studied group of
      known CRP-binding sequences, and a relatively newly identified group of genes
      known to be regulated by Lrp. The Lrp motif that we identify, based on 23 gene
      sequences, is similar to a previously identified motif based on a smaller data
      set, and to a consensus sequence of experimentally defined binding sites.
      Individual Lrp sites are evaluated and compared in regard to their regulation
      mode.

PMID- 8521048
TI  - Chromosome aberrations produced by ionizing radiation: Monte Carlo simulations
      and chromosome painting data.
AB  - Monte Carlo simulations are used to analyze the reshuffling of chromosome
      segments which occurs when DNA is damaged by ionizing radiation. Programs are
      based on either Sax's classic breakage-and-reunion model or Revell's exchange
      model for chromosome aberrations. The simulations quantify the predictions of the
      two models in complete detail, using only one adjustable parameter which
      corresponds to total radiation dose. While testing subroutines, new analytic
      results on the chromosome/arm/break method of classifying aberrations were
      obtained. The model predictions were tested by using three-color fluorescence in
      situ hybridization (FISH) 'chromosome painting' on human lymphocyte cells
      irradiated with gamma-rays. Some of the per-cell aberration frequencies were
      observed to be intermediate between the predictions of the two models. This
      result indicates proximity 'effects', due to localization of chromosome
      interactions in space and time. Predictions based on chromosome arm lengths were
      found to be in good agreement with experiment. Monte Carlo simulations are a
      powerful, flexible way to compare models of chromosome aberration production with
      experiments quantitatively, using a minimum of theoretical presumptions.

PMID- 8521049
TI  - alpha-Helix region prediction with stochastic rule learning.
AB  - We propose a new method, based on the theory of stochastic rule learning, for
      predicting alpha-helix regions in a given protein sequence. Our method (hereafter
      referred to as the SR method) produces stochastic rules, each of which assigns,
      to any region in an amino acid sequence, the probability that it is an alpha
      helix region. When learning a stochastic rule from a particular alpha-helix
      region, our method makes use of positive training examples obtained from a number
      of regions that are homologous to that region. Each stochastic rule is optimized
      using the minimum description length (MDL) principle, and such optimized
      stochastic rules are used to predict alpha-helix regions of any given protein
      sequence. In our experiments, using 25 proteins selected from the HSSP database
      as training examples, we applied the SR method to the problem of predicting alpha
      helix regions in test examples, which consisted of > 5000 residues with 38% alpha
      helix content. Each of these test examples possesses < 25% homology to any
      proteins in the training and other test examples. Our method achieved 81% average
      prediction accuracy for the test examples; this compares favorably to Qian and
      Sejnowski's method, which attains no more than 75% average accuracy, and further
      which compares to Rost and Sander's method which has proven to be one of the best
      secondary structure prediction methods.

PMID- 8521050
TI  - Representing inter-residue dependencies in protein sequences with probabilistic
      networks.
AB  - A new method for representing a local region of a protein sequence as a
      probabilistic network is proposed. The method produces, from a large number of
      examples of a local region, a network which describes dependencies that exist
      among amino acid residues in the region. The network is constructed using the
      greedy-search algorithm based on the minimum description length (MDL) principle.
      In our experiments, we construct a probabilistic network of the EF-hand motif
      domain in calcium-binding proteins. Experimental results show that our method
      provides a visual aid to understanding the inter-residue dependencies of those
      regions using a probabilistic network, and the network captures several important
      features which are peculiar to the motif.

PMID- 8521051
TI  - SAMSON: a software package for the biopolymer primary structure analysis.
AB  - The SAMSON package is a tool for advanced analysis of primary DNA, RNA and
      protein structures. The package consists of 16 programs performing statistical
      analysis and comparison of biopolymer sequences, search for homologies,
      translation of DNA and RNA sequences into amino acid sequences, splicing of RNA
      sequences and restriction map construction, recognition of functionally related
      sites in biopolymer molecules, textual analysis of DNA and RNA regulatory sites
      and prediction of intermolecular hybridization sites in DNA and RNA molecules.

PMID- 8521052
TI  - A computer program to aid the sequencing of peptides in collision-activated
      decomposition experiments.
AB  - A computer program named MSEQ, based on graph theory has been implemented to aid
      the sequencing of peptides from collision-activated decomposition (CAD) spectra.
      Input data required by this program are: the molecular weight of the peptide, the
      list of the masses of the daughter ions and the masses of the N- and C-terminal
      groups. The output comprises a list of the most likely sequences with their
      respective scores and the assignments of the daughter ions. A set of
      probabilities for each fragment ion was computed from hundreds of CAD spectra
      obtained from our mass spectrometer. To date many peptides have been sequenced in
      our laboratory with the help of this program, and in most of them the real
      sequence ranks among the five top sequences. The program is able to differentiate
      isobaric amino acids such as leucine and isoleucine when the side-chain
      fragmentation appears in the spectrum. A criterion is used to discard those
      sequences that match the spectrum poorly from the earliest steps. The program is
      fast and consumes no memory.

PMID- 8521053
TI  - SUBIM: a program for analysing the Kabat database and determining the variability
      subgroup of a new immunoglobulin sequence.
AB  - Although various programs are available to extract all the information included
      in protein sequence databases, none is dedicated to immunoglobulins. For this
      purpose, we designed a program, SUBIM, which is adapted to the Kabat database
      specialized in immunoglobulin sequences. Besides all the possibilities of any
      database searching program, SUBIM analyses new sequences of variable regions and
      determines the variability subgroup they belong to. It also numbers the new
      sequence according to the system established by Kabat and co-workers for an
      easier comparison with the other immunoglobulins, thus realizing an automatic
      alignment with other members of a given type of immunoglobulin chain. This
      program is largely machine independent and requires very little memory, and
      should help biochemists concerned with new immunoglobulin sequences.

PMID- 8521054
TI  - MitoProt, a Macintosh application for studying mitochondrial proteins.
AB  - The paper describes the Macintosh program MitoProt, which is suitable for
      studying mitochondrion-related proteins. MitoProt supplies a series of parameters
      that permit theoretical evaluation of mitochondrial targeting sequences, as well
      as calculation of the most hydrophobic fragment of 17 residues in the sequence,
      and a new parameter called mesohydrophobicity. The last two calculations are
      important for predicting the putative importability of a protein into
      mitochondria. Taken together, targeting sequence and hydrophobicity
      characteristics enable one to predict whether a given protein could be
      mitochondrial when no previous information on the nature of the sequence is
      available.

PMID- 8521055
TI  - DNASTAT: a Pascal unit for the statistical analysis of DNA and protein sequences.
AB  - DNASTAT is a collection of Pascal routines for researchers who develop their own
      application programs for statistical analysis of DNA and protein sequences.
      Dynamic and file-based data structures allow users to process sets of sequences
      by simple loop control without limitations on the number of sequences and their
      individual sizes. This frees the programmer from potentially error-prone tasks
      like dynamic memory allocation and controlling array sizes. Sequences can be
      stored in databases along with biological and statistical attributes. Individual
      sequences can be accessed by column name and row number as with spread-sheets.
      DNASTAT allows large sets of sequences to be processed using a PC with standard
      configuration. Its small size, simplicity and free availability make it
      attractive to students of mathematical biology. Use of DNASTAT is illustrated by
      two sample programs that generate a database of coding regions from the GenBank
      entry of the tobacco chloroplast genome. A version of DNASTAT written in ANSI-C
      for PCs and Unix workstations is also available.

PMID- 8521056
TI  - SUBTRACT: a computer program for modeling the process of subtractive
      hydridization.
AB  - We report on a new software tool, SUBTRACT, which allows the analysis of the
      possible strategies for an experiment based on a mathematical model of
      subtractive hybridization. The program helps the experimenter choose the optimal
      strategy and conditions for performing the reaction. The program allows the
      modeling of cDNA and genomic subtraction for different types of target DNA.
      SUBTRACT offers a friendly interface for the investigation of the dynamics of the
      process of subtractive hybridization, and for modifying different parameters and
      initial conditions. SUBTRACT allows the user to plot the values of interesting
      quantities as a function of the reaction time. The program runs under the Unix
      operating system on Sun-compatible computers.

PMID- 8521057
TI  - The chemical revolution and the art of healing.

PMID- 8521058
TI  - Pathology and treatment: the case of ulcers.

PMID- 8521059
TI  - Changing fashions in therapeutics.

PMID- 8521060
TI  - Therapeutic method in the later Middle Ages: Arnau de Vilanova on medical
      contingency.

PMID- 8521061
TI  - Making sense of therapeutics in seventeenth-century New England.

PMID- 8521062
TI  - Evaluation of intrauterine growth retardation in the fetus and neonate: are
      simple-minded methods good enough?

PMID- 8521063
TI  - Pubertal maturation of the internal genitalia.

PMID- 8521064
TI  - Can we be more confident about identifying a varicocele by clinical examination
      or by ultrasound?

PMID- 8521065
TI  - An adjustable fetal weight standard.
AB  - The monitoring of fetal weight is an important aspect of antenatal care. To
      construct an individually adjustable standard, we developed a model to link the
      predicted birth weight to a fetal weight curve which outlines how this weight is
      to be reached in an uncomplicated pregnancy. A formula was derived which
      describes the median fetal weight at each gestation as a proportion of the
      optimal term weight, and also defines the 90th and 10th centile curves as normal
      limits. We analyzed a birth weight database of 38,114 singleton, routine
      ultrasound-dated pregnancies resulting in term deliveries. By stepwise multiple
      regression analysis, we derived coefficients for the factors that act as
      variables on term birth weight in our population. Apart from gestational age and
      sex, the maternal height, weight at first visit, ethnic group, parity and smoking
      all have significant and independent effects on birth weight. The variation due
      to ethnic group appears to be physiological in this population. Smoking is
      associated with a reduction in birth weight, which is independent of maternal
      physique and related to the number of cigarettes per day as reported at the first
      visit. We have developed a software program which calculates, on the basis of
      pregnancy variables entered at the first visit, an adjusted normal range for
      fetal size. This can be printed out as a chart and used for antenatal
      surveillance of growth.

PMID- 8521066
TI  - Pubertal maturation of the internal genitalia: an ultrasound evaluation of 166
      healthy girls.
AB  - Pelvic ultrasound is an important tool in the management of children with
      disturbances of pubertal development; interpretation requires an understanding of
      the normal relationship between maturation of internal genitalia and the
      appearance of secondary sex characteristics. We performed pelvic ultrasound
      examinations in 166 healthy females aged 6.4-25.4 years, and related uterine and
      ovarian volumes and size of follicles to age and pubertal stage. We demonstrated
      growth of the uterus and ovaries before the appearance of breast development and
      pubic hair growth. In prepubertal girls, uterine and ovarian growth was related
      to height (p = 0.008 and p = 0.010, respectively). From breast stages 1-5, median
      uterine and ovarian volumes increased from 1.6 ml to 43 ml, and from 1.2 ml to
      7.3 ml, respectively (p < 0.0001). Uterine growth continued several years after
      menarche. Postmenarcheal uterine growth was related to the number of years after
      menarche (p < 0.001), but not to height, weight or age. Follicles were seen in
      86% of prepubertal girls and in 99% of pubertal girls. Follicles up to 8 mm in
      diameter were observed in prepubertal girls. Maturation of the internal genitalia
      begins before the onset of clinical puberty, and extends well into the second
      decade.

PMID- 8521067
TI  - Sonographic incidence of polycystic ovaries in a gynecological population.
AB  - The prevalence of polycystic ovaries in a large population of 1078 women of
      reproductive age was determined by pelvic ultrasonography. The ovarian ultrasonic
      appearance of 183 (17%) women met the morphological criteria of polycystic
      ovaries. Of these women, 147 (80.3%) had irregular cycles (group A) and 36
      (19.7%) had normal cycles (group B). The remaining women constituted the control
      group. Ovarian volume was calculated in all women in whom at least one ovary was
      visualized. Serum levels of luteinizing hormone (LH), follicle stimulating
      hormone (FSH) and testosterone were measured in 124 women from group A, 25 from
      group B and 50 controls. Mean ovarian volume was statistically higher in both
      group A (13.4 ml) and group B (11.8 ml) than in the control group (6.2 ml). Mean
      LH/FSH ratio and mean testosterone values were statistically higher in group A
      only (2.1 and 1.1 ng/ml, respectively) compared with the mean values in the
      control group (0.7 and 0.7 ng/ml, respectively). Obesity and hirsutism were more
      common in group A than in group B and the controls. Screening the ovaries in
      women of reproductive age and subsequent assessment of morphology in polycystic
      ovaries can aid in the diagnosis of this condition in patients who may have a
      varied clinical presentation.

PMID- 8521068
TI  - The ultrasound diagnosis and clinical significance of varicocele.
AB  - A study was carried out to determine the relationship between clinically
      diagnosed and ultrasound-diagnosed varicoceles in 151 men with normal and
      abnormal semen analysis. In only 60 cases (40%) was the clinical diagnosis
      confirmed by ultrasound. Of the men with ultrasound-diagnosed varicocele, 14%
      were found to have a normal semen analysis compared to 31% of men without a
      varicocele, and this difference was statistically significant (p < 0.05).
      Bilateral varicoceles were associated with an even greater chance of having an
      abnormal semen analysis (p < 0.01), and with a significantly (p 0.05) decreased
      chance of spontaneous pregnancy. These men and also men with unilateral
      varicocele, whose partners have a relative cause of female subfertility, may
      benefit from earlier intervention for the treatment of their subfertility.

PMID- 8521069
TI  - Endometrial thickness, morphology, vascular penetration and velocimetry in
      predicting implantation in an in vitro fertilization program.
AB  - A total of 96 women undergoing in vitro fertilization (IVF) treatment were
      studied on the day of human chorionic gonadotropin (hCG) administration by
      transvaginal ultrasonography with color and pulsed Doppler ultrasound. We
      assessed endometrial thickness, endometrial morphology, presence or absence of
      subendometrial or intraendometrial color flow, intraendometrial vascular
      penetration and subendometrial blood flow velocimetry on the day of hCG
      administration and related the results to pregnancy rates. The overall pregnancy
      rate was 32.3% (31/96) and there was no significant difference between the
      pregnant and non-pregnant groups with regard to endometrial thickness,
      subendometrial peak systolic blood flow velocity (Vmax) or subendometrial
      pulsatility index (PI). The pregnancy rates based on endometrial morphology were
      not significantly different, being 17.6% (3/17), 33.3% (2/6) and 35.6% (26/73)
      for types A (hyperechoic), B (isoechoic) and C (triple-line) endometria,
      respectively. In eight (8.3%) patients, subendometrial color flow and
      intraendometrial vascularization were not detected. This absence of blood flow
      was associated with failure of implantation (p < 0.05). The pregnancy rates
      related to the zones of vascular penetration into the subendometrial and
      endometrial regions were: 26.7% (4/15) for Zone 1 (subendometrial zone), 36.4%
      (16/44) for Zone 2 (outer hyperechogenic zone) and 37.9% (11/29) for Zone 3
      (inner hypoechogenic zone), and were not significantly different. Of cycles with
      type A endometrium, 23.5% (4/17) had absent subendometrial color, which was
      greater than the frequency of absent color in the type C endometrium (4.1%, p =
      0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521070
TI  - Differential diagnosis of breast lesions by color Doppler.
AB  - Color Doppler allows flow detection in small tumor vessels. Due to the
      vascularity associated with the growth of malignancies, this method can be used
      to differentiate between benign and malignant breast lesions. In order to study
      the typical flow characteristics, we investigated multiple Doppler flow
      parameters. A UM9 HDI (ATL) was used with a linear transducer L 10-5. The number
      of tumor vessels and the mean, maximum and total flow velocity were measured in
      325 benign and 133 malignant lesions and showed highly significant differences (p
      < 0.0001). Flow profiles (resistance index and systolic/diastolic frequency
      ratio) showed a large overlap and did not allow accurate tumor differentiation
      when mean and minimum values were analyzed. Surprisingly, the maximum resistance
      index and systolic/diastolic frequency ratio were significantly higher in
      carcinomas than in benign lesions, but the overlap of the values was wider than
      the flow velocity measurements. Using the vessel number and the total tumor
      vascularity, 90% of all lesions could be differentiated. A difficulty that we
      encountered was that a few cancers have very low flow values and some of the
      proliferative benign lesions can have increased flow.

PMID- 8521071
TI  - Differential diagnosis of mammary tumors with vocal fremitus in sonography:
      preliminary report.
AB  - During sonographic examinations using the new color Doppler technique, maximum
      entropy method (MEM), it was discovered, by chance, that artefacts which are
      produced by vibrations of the thorax can be used to differentiate between
      malignant and benign breast lesions. These artefacts, in the form of small color
      pixels, can either be brought about by vocal fremitus known from internal
      medicine or by humming in a low tone. In the case of malignant tumors, the color
      pixels are visible in the middle of the sonographically portrayed tumor as well
      as in the surrounding tissue, whereas in benign tumors the artefacts are only
      found in the surrounding tissue and are quite clearly not present in the center
      of the tumor. On the preoperative day, 95 patients with 46 benign and 49
      malignant lesions were examined using the method described above. In 91% the
      differential diagnosis was in accordance with the histological results. In seven
      cases a benign lesion was classified before the operation as malignant and in two
      cases malignancy was incorrectly diagnosed as benign. Our explanation of the
      phenomenon is based on the fact that most benign tumors exhibit a restricted
      growth and form a clear-cut boundary with the surrounding tissue, so the
      vibrations are not conducted into the tumor. In contrast, malignant lesions grow
      by infiltrating the surrounding tissue, allowing the vibrations to be conducted
      into the tumor, where they can be demonstrated as small color pixels.

PMID- 8521072
TI  - B-mode color sonographic images in obstetrics and gynecology: preliminary report.
AB  - The standard B-mode image shows 256 levels of gray, but the human eye can only
      differentiate 8-16 shades of gray. Color vision theoretically has several
      advantages in comparison with gray scale, because the human eye can distinguish
      128 fully saturated hues and about 350,000 shades. In 1992, B-mode color maps
      were introduced in our clinical practice, to establish whether this technology
      was able to detect the smallest contrast differences better than the gray-scale
      map and therefore to increase diagnostic accuracy. This paper describes our
      experience with the technique and reports B-mode color images of clinical
      complications in obstetrics and gynecology. We use the color figures to
      illustrate this new technology and to demonstrate the advantages of the increased
      sensitivity of the human eye to color in different clinical situations. We
      conclude that the use of B-mode color maps does not change the ultrasonic
      diagnosis, but does enhance our ability to study and evaluate the morphological
      structure of different tissues, compared to the gray-scale map alone.

PMID- 8521073
TI  - Single umbilical artery: a clinical enigma in modern prenatal diagnosis.

PMID- 8521074
TI  - Detection of ovarian malignancy--authors' reply.

PMID- 8521075
TI  - In vitro yeast (Saccharomyces cerevisiae) presqualene and squalene synthesis
      related to substrate and cofactor availability.
AB  - Squalene synthase catalyses the synthesis of squalene from trans-farnesyl
      diphosphate in 2 separate steps requiring NAD(P)H. The kinetics of this enzyme in
      different fractions extracted from a wild-type Saccharomyces cerevisiae were
      studied. Although this protein is known to be a membrane-bound enzyme, we have
      found a cytosolic squalene synthase activity besides the microsomal enzyme. A
      spectrophotometric enzyme assay, not involving isotopic labelling, was
      established. The relative synthesis of presqualene and squalene was evaluated by
      using different substrate and cofactor concentrations during the incubation. The
      involvement of a single catalytic site promoting the 2 reactions of squalene
      synthesis is suggested.

PMID- 8521076
TI  - Multienzymatic non ribosomal peptide biosynthesis: identification of the
      functional domains catalysing peptide elongation and epimerisation.
AB  - Peptide synthetases are multienzymatic complexes that synthesize bioactive
      peptides molecules by the thiotemplate mechanism. Comparison of the known
      sequences of peptide synthetases led us to the identification of a 350 amino
      acids domain catalysing elongation and containing the motif HHxxxDG. This motif
      is present as many times as acyltransfer or epimerisation reactions occur during
      biosynthesis of the peptide. The distance between this motif and the
      phosphopantetheinyl attachment site is nearly invariant. An identical motif is
      found in other enzymes effecting acyl transfer such as chloramphenicol
      acetyltransferase from Tn9 and dihydrolipoamide acyltransferase. Altogether, the
      HHxxxDG motif may constitute the signature of a superfamily sharing a common
      catalytic mechanism based on the acid-base properties of the second histidine for
      effecting acyl transfer or peptide epimerisation.

PMID- 8521077
TI  - Dual specificity of casein kinase II from the yeast Yarrowia lipolytica.
AB  - In the case of protein kinases, and especially in the case of casein kinase II
      (CKII), a link has been found between the type of the amino acids
      autophosphorylated and the targeted amino acids on the substrates. In the
      presence of Mg2+, CKII from the yeast Yarrowia lipolytica is autophosphorylated
      on serines and threonines, and a serine threonine kinase activity is found
      predominantly when casein is used as substrate. In the presence of Mn2+, CKII
      autophosphorylation is inhibited on serines, and autophosphorylation on
      tyrosines, negligible in the former case, becomes significant. Tyrosine
      phosphorylation is then found to occur on casein. Mn2+ transforms CKII into a
      protein kinase with dual specificity, shifting its specificity from
      serine/threonine kinase towards a serine/threonine and tyrosine kinase. Mn2+
      decreases the level of serine and threonine phosphorylation observed, while on
      the other hand promoting tyrosine kinase activity.

PMID- 8521078
TI  - Heterogeneity within the first constant segment of the major outer membrane
      protein gene in Chlamydia trachomatis serovar D/Da distinguishes 2 lineages.
AB  - Restriction fragment length polymorphism of the major outer membrane protein gene
      (ompl) was studied in 73 epidemiologically unrelated Chlamydia trachomatis
      serovar D (n = 64) and Da (n = 9) strains isolated between 1983 and 1991 in
      various european countries from patients suffering from sexually transmitted
      diseases, as well as 3 reference strains D/IC-Cal-8 (USA), D/UW3 (UK) and Da/TW
      448 (Taiwan). Among these strains, 5 different genotypic groups were
      distinguished: 3 for the serovar D strains and 2 for the serovar Da strains.
      Comparisons of the complete ompl nucleotide sequence of 1 member of each group
      revealed 2 distinct lineages, independently of the D/Da classification,
      presumably as the result of an intragenic DNA recombination event within the
      first constant segment. The observed ompl genetic diversity of serovar D/Da
      strains in regions involved in T- and B-cell responses might add another level of
      complexity to the design of a subunit vaccine.

PMID- 8521079
TI  - [Functional properties of a new line of immortalized human endothelial cells].
AB  - An immortalized human endothelial cell line was obtained by transfecting
      umbilical vein endothelial cells in primary culture with plasmid pMK16 containing
      SV40 replicated origin defective gene. The essential functional properties
      demonstrated in these immortalized human endothelial cells also retaining the
      classical phenotypical characteristics of endothelial cells in primary culture
      are: (1) endothelin-1 secretion; (2) capacity to convert big endothelin-1 into
      endothelin-1; (3) the capacity to secrete IL1 beta and IL6 interleukins both
      spontaneously and after lipopolysaccharide (LPS) stimulation; (4) arginine
      transfer from the extracellular to the intracellular medium. Such stable cell
      line could facilitate studies of regulation of endothelin-1 production; (5) No
      synthase activity; (6) binding and metabolisation of acetylated low-density
      lipoproteins.

PMID- 8521080
TI  - Identification of a new exon of the brain microtubule-associated protein 2.
AB  - The 5'-region of the transcripts encoding the HMW-(MAP2b) and LMW-(MAP2c)
      microtubule associated proteins in the brain was amplified by RT-PCR. The
      sequencing of cloned PCR fragments allowed to identify a new variant of brain HMW
      MAP2 which contained, compared to MAP2b, an insertion of 246 bp located
      downstream the 5'-junction between MAP2b and MAP2c and that does not alter the
      open reading frame of MAP2b. The number of amino acid residues encoded by this
      insertion increases the molecular weight by 8.5 kDa i.e. corresponds to the
      difference in apparent size between MAP2a and MAP2b. A LMW-MAP2 PCR amplification
      product containing this insertion has been also identified. Genomic Southern blot
      analysis confirmed that this region belongs to the MAP2 gene and is located on a
      single exon.

PMID- 8521081
TI  - [Effects of dietary fats of vegetable and animal origin on lipid synthesis in
      pigs].
AB  - We have compared the effect of dietary fats, unsaturated (rapeseed oil: RO) or
      saturated (cow milk: CM), on growth performance, lipogenesis and fatty acid
      composition of backfat. Both group had the same food intake and growth
      performance. Nevertheless, the percentage of body fat increases with the diet RO
      (P < 0.05). Lipogenesis enzyme activities of backfat were greater with RO than
      with MC. Then, it appeared that pigs fed diets containing high level of
      unsaturated fat with long-chain fatty acids have both greater lipogenesis and
      carcass fatness as opposed to pigs fed diet containing saturated fat with medium
      chain fatty acids. The fatty acids composition of lipids deposited with RO diet
      may alter the technological qualities of adipose tissues and that of meat.

PMID- 8521082
TI  - [HLA-DQ genotyping using a modified technique of PCR-RFLP: application to HLA
      DQA1 gene].
AB  - Since 1989, several HLA-DQA1 PCR-RFLP genotyping protocols have been published.
      These methods require complete digestion of the PCR products and determination of
      the restriction fragments length. The HLA-DQA1 PCR-RFLP genotyping protocol
      describe here uses one amplification step through PCR, digestion of the PCR
      products with 8 restriction endonucleases, and determination of the fragments
      size after polyacrylamide gel electrophoresis. Five of the enzymes, having no
      more than one restriction site in each allele (ApaLI, HphI, BsaJI, FokI and
      MboII), allow distribution of all the genotypes in 19 allelic-combination groups
      on the base of the digestion pattern: cut/not cut. Three additional enzymes
      (MnlI, DdeI and RsaI), having at least 2 restriction sites in each allele, are
      used to assign the genotype in each allelic-combination group on the base of the
      restriction fragments length observed. Eight of the 13 alleles, 36 of the 91 HLA
      DQA1 genotypes could be characterized. Four to 8 samples could be characterized
      each day, including DNA extraction. The number of endonucleases used could act as
      internal control of enzymatic activities and the genotyping protocol can include
      new HLA-DQA1 alleles without modification of the experimental steps. This
      protocol can be applied easily in a laboratory without specific technical
      training or specific equipment.

PMID- 8521083
TI  - Localized proton magnetic resonance spectroscopy of the brain differentiates the
      inborn metabolic encephalopathies in children.
AB  - Localized brain proton magnetic resonance spectroscopy (MRS) has been performed
      using a STEAM (stimulated echo-acquisition mode) method with a short-echo time
      (20 ms) in 10 children suffering from different lysosomal diseases, 6 boys with X
      linked adrenoleukodystrophy (X-ALD) and 5 healthy children. Metabolic data from
      localized spectra were processed by principal component analysis (PCA) of 7
      metabolic variables recorded on the MR spectra. PCA allows to delineate different
      clusters corresponding to the 2 pathological groups which are separated from each
      other and from the control group. The position of each spectrum on the patient
      map correlates with the clinical data and to the evolution of the patients
      subjected to a follow-up. These results also confirm the metabolic features
      characterizing the pathologies of the lysosome (increase in inositol) and the
      peroxisome (increase in choline and free lipids). PCA constitutes an alternative
      to the classical statistical methods to analyze and compare metabolic
      modifications in small populations of patients and allows to identify the most
      critical parameters defining the organization of the pathological populations.
      This analysis clearly increases the discrimination among pathologies based on the
      metabolic profiles obtained by MRS.

PMID- 8521084
TI  - [Free radicals as second messengers].
AB  - Cytokines such as IL-1 or TNF-alpha induce a specific cellular responses through
      the activation of a transcriptional factor, NF kappa B. This activation requires
      the phosphorylation of an inhibitory subunit, I kappa B, which relies upon an
      intracellular production of reactive oxygen intermediates. Peroxides, but also
      the increase of the GSSG/GSH ratio are assumed to play a major role in this
      process. There is presently a good agreement on the overall scheme of IL-1 and
      TNF-alpha activation and on the involvement of reactive oxygen intermediates in
      the corresponding signal transduction cascades. However several questions
      regarding the molecular mechanisms involved in particular steps of these cascades
      remain largely unresolved: how and at which subcellular level, do the cells
      produce these reactive oxygen intermediates that will contribute to NF kappa B
      activation in response to IL-1 or TNF-alpha? What are the kinases/phosphatases,
      being modulated by peroxides and what is the contribution of high GSSG levels to
      NF kappa B activation? In this paper, we will briefly overview this basic issue
      in cell biology and highlight some of the recent experimental data that will help
      us to understand the exact role of reactive oxygen intermediates in NF kappa B
      activation and the molecular mechanisms involved.

PMID- 8521085
TI  - [Effect of the liposolubility of free radical scavengers on the production of
      antigen P24 from a HIV infected monocytic cell line].
AB  - A large body of evidence indicates that AIDS may be the consequence of a virus
      induced antioxidant deficiency and implicates reactive oxygen species (ROS) in
      the pathogenesis of HIV infection. The high level of antigenic acid and cytokines
      activities in AIDS results in the production of superoxides (O2-), hydrogen
      peroxide (H202) and hydroxyl radicals (OH). HIV-infected T cells display low
      levels of SOD, catalase, thioredoxin and glutatione peroxidase rendering them
      susceptible to undergo apoptosis. Induction of NF kappa B and HIV replication are
      at least in part dependent on reactive oxygen intermediates. We examined the
      protective effects of two antioxidants. Ferulic Acid (FA) and Ethyl Ferulate (EF)
      at 1, 5, 10, 10 microM on the TNF induced HIV activation in the chronically
      infected promonocytic U1 cell line. FA and EF at 5 microM elicit a marked
      decrease of HIV p24 release. HIV inhibition was greater after pretreatment with
      EF than with FA. At these concentrations, no cytotoxicity was observed. When SOD
      (100 UI) was combined with EF and FA no more inhibition was observed. But when
      SOD was added alone, it induced a marked inhibition (30%). This class of drugs
      may present potential interest as antiviral agents or as adjuvant therapy in
      AIDS.

PMID- 8521086
TI  - [Protection of oxidation of LDL by nitric oxide: implication in atherogenesis].
AB  - Superoxide (O2-) and nitric oxide (.NO) are free radicals which are known to
      react together leading to peroxynitrite anions that can decompose to form
      nitrogen dioxide (NO2) and hydroxyl radical (OH degrees). .NO has been reported
      to have a dual effect on LDL oxidation (pro or antioxidant). In the present study
      we have investigated in vitro the action of exogenous .NO on human LDL oxidation
      promoted by oxygen, copper or (2,2'-azobis (2-aminodinopropane
      hydrochloride)(ABAP). .NO was given as NO donnor (sodium nitroprussiate or S
      nitroso-L-glutathione) from 10 to 500 microM. Oxidation of LDL was measured by
      monitoring continuously conjugated diene formation at 234 nm. Exogenous .NO
      inhibited in a dose dependent manner the progress of spontaneous LDL oxidation.
      Copper--or ABAP--induced oxidation were characterized by lag, propagation and
      decomposition phases. Exogenous .NO decreased the propagation rate of LDL
      oxidation and the level of maximal diene production. These effects are different
      of these of alpha-tocopherol, a chain-breaking antioxidant. In our experimental
      conditions, .NO exhibited antioxidant activities. In vivo, the continuous release
      of endogenous .NO could protect LDL from cell-induced oxidation.

PMID- 8521087
TI  - [Does nitric oxide stress exist?].
AB  - Ten years ago, the term "oxidative stress" (sigma -O2) was created to define
      oxidative damage inflicted to the organism. This definition brings together
      processes involving reactive oxygen species production and action such as free
      radical production during univalent reduction of oxygen within mitochondria,
      activation of NADPH-dependent oxidase system on the membrane surface of
      neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to
      chemical and physical agents in the environment. Since the discovery of the
      nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric
      oxide generation are generally classified as oxidative stress. Indeed, products
      of the reaction of NO and superoxide lead to oxidants such as peroxinitrite,
      nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell
      mediated immune reactions and defence of the intracellular environment against
      microbiol invasion. However NO can also regulate many biological reactions and
      signal transduction pathways that lead to a variety of physiological responses
      such as blood pressure, neurotransmission, platelet aggregation, endothelin
      generation or smooth muscle cell proliferation. Then the uncontrolled NO
      production can lead to a variety of physiological and pathophysiological
      responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and
      production of cGMP: overstimulation of the inducible L-arginine to L-citrulline
      and NO pathway by bactericidal endotoxins and cytokines has been shown to promote
      undesired increases in vasodilatation, which may account for hypotension in
      septic shock and cytokine therapy. stimulation of auto-ADP-ribosylation and
      modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP
      independent mechanism: by this way, NO in excess can strongly inhibits this
      important glycolytic enzyme and reduce the cellular energy production. inhibition
      of ribonucleotide reductase: extensive inhibition of this key enzyme in DNA
      synthesis in the presence of large amounts of NO could lead to important
      antiproliferative effects; inhibition of cytochrome P450-dependent metabolism: in
      Kupffer cells and hepatocytes, LPS-induced overproduction of NO has been shown to
      inhibit cytochrome P450-dependent metabolism and to mediate the suppression of
      hepatic metabolism. Moreover, NO synthetized in the peripheral nervous system is
      known to mediate nonadrenergic noncholinergic (NANC) neurotransmission.
      Overstimulation of NO synthases might therefore contribute to pathophysiological
      states such as: gastrointestinal motility, reflux oesophagitis, asthma, adult
      respiratory distress syndrome (ARDS) and chronic pulmonary artery hypertension.
      To these NO-mediated biological functions, one could add the biological effects
      of NO-derivatives such as N-nitrosocompounds, which act as carcinogenic agents,
      or C-nitrosocompound which were recently used as "zinc-ejecting" agents to
      inhibit HIV-1 infectivity of human T-lymphocytes.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8521088
TI  - [Potential antioxidative effects of pentoxifylline].
AB  - Pentoxifylline (PTX) is a methylxanthine derivative with hemorrheologic
      properties. PTX decreases neutrophil degranulation and tumor necrosis factor
      production. We investigated the properties of the drug as a hydroxyl radical
      scavenger. The aim of this study was to assess the ability of PTX to inhibit
      visible fluoroescence generation in albumin incubated with 50 microM cupric
      chloride and 880 microM hydrogen peroxide for 3 h at 37 degrees C. PTX inhibited
      visible fluorescence generation (ex 360, em 454 nm) by 11% at 50 microM, 13% at
      100 microM and 22% at 200 microM. In conclusion, PTX inhibited fluorescence
      generation in proteins induced by copper/hydrogen peroxide and has potential
      beneficial effects by protecting proteins against oxidative damage by reactive
      oxygen species.

PMID- 8521089
TI  - [Preferential tumoral phototoxicity of chloroaluminum phthalocyanine in
      photodynamic therapy of human leukemic cells].

PMID- 8521090
TI  - [Auto-oxidation or brain homogenate: research of oxidizing agent and targets.
      Comparison with liver homogenate].
AB  - The aim of this study was to determine: 1) the source of Thiobarbituric Reactive
      Substances (TBARS) spontaneously produced during rat brain homogenate incubation;
      2) the cellular components involved; 3) the reason why brain and liver
      homogenates did not have the same behaviour. Measurements of TBARS,
      Polyunsaturated Fatty Acids (PUFAs), aldehydes coming from PUFAS breakdown,
      vitamin E and Schiff's bases levels were performed on brain and liver
      homogenates, membrane fractions (Mb) and medium containing soluble cytoplasmic
      components (CS). Mb and CS were prepared by differential centrifugation. Brain
      homogenate incubation, contrary to liver homogenate, led to an increase in TBARS
      amount, while PUFAS, aldehydes and vitamin E levels remained unchanged. No TBARS
      accumulation arose when Mb or CS were separately incubated. However, it was of
      interest to note that liver or brain incubation of Mb with CS led to an
      overproduction of TBARS. These results suggested that spontaneous oxidation of
      brain homogenate was not due to lipid peroxidation. On the other hand, the fact
      that, contrary to the liver homogenate, liver Mb incubated with CS led to an
      increase in TBARS level, supports the idea that a "protective agent" was
      eliminated during centrifugation. It can be speculated that this "agent" is not
      effective in the brain.

PMID- 8521091
TI  - [Lipid peroxidation in the presence of inorganic compounds. Relation to oxidative
      stress mechanisms].
AB  - Oxidizing activity study of inorganic compounds is based on a mechanistic
      approach. This approach implies research of the capacity of these materials,
      after interaction with molecular oxygen, to generate activated oxygen species
      (AOS) in aqueous medium. These electrophilic species are able to participate in
      oxidative stress processes and some AOS differ in their oxidizing power; highly
      oxidizing species (A*) and entities (P*) less oxidizing than A*. These AOS are
      capable of initiating linolenic acid peroxidation leading to formation of
      different degradation products such MDA, monoaldehydes, conjugated dienes and
      trienes, hydroperoxydes, and ethane. The detection of these products allows to
      reveal the presence of AOS. Our data show that the global assessment of lipid
      peroxidation should be established from the whole of formed peroxidation products
      and not from one type of degradation products.

PMID- 8521092
TI  - [Lipid peroxidation, production of PGE2 and cellular mortality induced by UV in
      cultured human skin fibroblasts].
AB  - UV irradiation induces lipid peroxidation (LPO) and cell damage. The aim of the
      present work was the study of UVB radiation effects on cultured human skin
      fibroblasts, concerning LPO, prostaglandine E2 (PGE2) formation and cell
      viability. The cells were exposed to 50, 100, and 150 mJ/cm2 of UVB irradiation.
      Cellular TBARS and supernatant fluorescent substances were measured
      spectrofluorimetrically. PGE2 was measured using an immunoenzymatic method. Cell
      viability was evaluated by the MTT test. All determinations were done after a 2 h
      incubation period post-irradiation. TBARS were increased for all doses of
      irradiation (p < 0.001). Fluorescent substances differed from controls at 50
      mJ/cm2 (p < 0.001). UVB at 100 and 150 mJ/cm2 decreased cellular viability (p <
      0.001). An increase of PGE2 was observed with UVB at 150 mJ/cm2 (p < 0.001).
      These results confirm the occurrence of LPO and cytotoxicity after UV
      irradiation; on the other hand, this study showed the formation of PGE2 induced
      by UV light on cultured human skin fibroblasts. We propose a relationship between
      these phenomena.

PMID- 8521093
TI  - [Kinetics of lipid peroxidation induced by UV beta rays in human keratinocyte and
      fibroblast cultures].
AB  - Lipid peroxidation has been implicated in skin damage by ultraviolet radiation.
      The aim of the study was to determine the kinetic of lipid peroxidation induced
      by ultraviolet beta (UVB) in adult keratinocytes and fibroblasts in culture. The
      keratinocytes were obtained from a single primary culture and the fibroblasts
      were in the same subculture (4 to 10 transfers). For UVB irradiation, the cells
      were maintained in a small volume of Hanks balanced salt solution and were
      irradiated (0.75, 1.5, 3 and 4.5 Jcm-2). Then cells were cultured for 3 to 48
      hours. Lipid peroxidation was estimated by free MDA determination in both
      extracellular medium and cells using a size exclusion chromatography coupled to
      an HPLC procedure. In addition, LDH release in culture media was evaluated as in
      indice of cytotoxicity. An increase of total free MDA was observed 3 hours after
      cell irradiation which was dose-dependent from 0.75 to 3 Jcm-2 for keratinocytes
      and fibroblasts. MDA was detected both in cells and in culture media. As soon as
      3 hours after irradiation 90% in total MDA was present in the culture media.
      Kinetic of lipid peroxidation: for 0.75 Jcm-2, an elevation of MDA was observed
      12 hours after irradiation in both cultures. A further increase in MDA was noted
      24 hours after fibroblasts irradiation but not in irradiated keratinocytes. LDH
      release in culture media increased with post irradiation time until 48 hours. The
      cytotoxic effect of UVB irradiation on keratinocytes and fibroblasts cultures was
      shown by an enhancement of lipid peroxidation which was detectable during 48
      hours after irradiation. An increase of LDH release was observed simultaneously.

PMID- 8521094
TI  - Who qualifies as a coauthor?

PMID- 8521095
TI  - Osteoma of the maxillary antrum.

PMID- 8521096
TI  - Trigeminal neuralgia and multiple sclerosis.

PMID- 8521097
TI  - Fractures of the mandible: the case for minimal intervention.

PMID- 8521098
TI  - Severe hemorrhage from a pigmented exophytic mass.

PMID- 8521099
TI  - Management of nonreducing temporomandibular joint disk displacement. Evaluation
      of three treatments.
AB  - OBJECTIVE: The purpose of this study is to evaluate the responses of patients
      with anterior disk displacement without reduction to natural course,
      stabilization splint, and surgery. STUDY DESIGN: Thirty-one patients refused any
      treatment (natural course group), 20 patients were treated with a stabilization
      splint (stabilization splint group), and 24 patients who had not responded to
      nonsurgical treatment for a mean period of 19.0 months underwent surgery
      (surgical group). The success rate was evaluated in each of the three groups.
      RESULTS: The success rate was 41.9% in the natural course group, 55.0% in the
      stabilization splint group, and 76.9% in the surgical group. CONCLUSIONS: No
      statistically significant benefit from treatment with a stabilization splint over
      no treatment was identified although both groups of patients experienced
      alleviation of discomfort. The patients who had not responded to nonsurgical
      treatment for a mean period of .19 months benefited from surgery.

PMID- 8521100
TI  - Failures in ridge reconstruction with hydroxyapatite. Analysis of cases and
      methods for surgical revision.
AB  - Misuse of hydroxyapatite for ridge reconstruction leads to problems in denture
      construction. The object of this article is to analyze cases that have failed to
      provide acceptable results and to discuss methods for surgical revision. The
      group under study was made of 30 patients treated originally in different centers
      (with one exception) with 34 attempts at ridge reconstruction for the 27
      mandibular cases and 3 maxillary ones. Only two mandibular cases received a skin
      graft. Three major problems were identified: (1) improper location of
      hydroxyapatite over the vestibular instead of the lingual or palatal sides of the
      ridge (27 of 30 cases); (2) poorly defined ridge form (26 of 30 cases); and (3)
      submucosal hydroxyapatite extrusion (15 of 30 cases). Splints or binding agents
      did not prevent these complications. Mandibular revision was accomplished by
      adding hydroxyapatite over the old material and onto the lingual side of the
      ridge. At a second stage, the floor of the mouth was lowered. As the vestibule
      was extended, material in excess was removed before skin graft application.
      Maxillary revision involved material removal from the vestibular side to allow
      the lining mucosa of the vestibule to return to a normal position.

PMID- 8521101
TI  - Use of rigid external fixation in fractures of the mandibular condyle.
AB  - In this article the use of a rigid external fixation system is proposed for the
      early treatment of condylar fractures. This method offers the advantage of not
      damaging the articular structures during reduction and allows early mobilization
      for a rapid recovery. In our Centre 28 patients have been treated with the rigid
      external fixation system, with good functional results. Of these 15 men and 13
      women, 22 had a monocondylar fracture and 6 had a bicondylar fracture. In all the
      cases there was complete recovery of the occlusal stituation and of the mouth
      opening; no patient surgically treated with this method has ever presented
      problems of a local or general nature. The purpose of this report was to evaluate
      the use of external fixation for the treatment of extracapsular condylar
      fractures with luxation of the fragment out of the glenoid cavity.

PMID- 8521102
TI  - Management of triangular fragments of the inferior border of the mandible.
AB  - Twenty-five cases of mandibular fractures with triangular fragments in the lower
      border were analyzed with respect to mode of treatment and rate of complication
      by infection. Fragments that remained unexposed and unreduced during treatment of
      the mandibular fractures were not complicated by infection, whereas about 50% of
      the fragments that were repositioned and fixed became infected. The study
      discusses the complexity of the physiopathology and management of these
      fragments. It appears that triangular fragments should be left unexposed.

PMID- 8521103
TI  - Possible identity of diffuse sclerosing osteomyelitis and chronic recurrent
      multifocal osteomyelitis. One entity or two.
AB  - On the basis of the findings of nine of our patients and our review of previously
      reported cases of diffuse sclerosing osteomyelitis and chronic recurrent
      multifocal osteomyelitis, we discuss the similarity of these two entities. Our
      nine patients had initially been given diagnoses of diffuse sclerosing
      osteomyelitis on the basis of their clinicopathologic findings. However,
      technetium 99m-MDP bone scans performed on four of them revealed multiple bone
      lesions leading to the diagnosis of chronic recurrent multifocal osteomyelitis.
      Furthermore, no clear difference between clinical features in the patients with
      multiple bone lesions and those in the patients with diffuse sclerosing
      osteomyelitis was found. We conclude that diffuse sclerosing osteomyelitis is an
      expression of chronic recurrent multifocal osteomyelitis.

PMID- 8521104
TI  - Evaluation of medical consultations in a predoctoral dental clinic.
AB  - OBJECTIVE: A patient's medical condition can affect the delivery of dental care.
      Medical consultation is indicated for dental patients whose medical history is
      uncertain or when physical assessment may indicate an untreated medical problem.
      The aims of this study were to evaluate the use of medical consultation and
      determine how it affects dental treatment plans in a predoctoral dental clinic
      program. STUDY DESIGN: Reviews of 147 medical consultation requests were
      performed. RESULTS: The main reasons for medical consultations were
      cardiovascular assessment (51.5%) and diabetic status determination (12.6%). In
      the cardiovascular assessment category, hypertension (48.1%) and heart murmur
      (17.9%) were primary concerns. Main dental concerns were the need for
      preoperative antibiotic prophylaxis (33.3%) and the use of vasoconstrictors
      (20.4%). Overall, 32.1% of medical consultations resulted in an alteration in
      dental treatment plans. As a result of medical consultations, 8% commenced their
      medical management. CONCLUSIONS: These results indicated that medical
      consultations could reduce the medical risk associated with dental procedures and
      unnecessary antibiotic prophylaxis. Therefore for many dental patients, good
      communication between dentists and physicians is essential for adequate care.

PMID- 8521105
TI  - Atypical migratory stomatitis and Munchausen syndrome presenting as periorbital
      ecchymosis and mandibular subluxation.
AB  - Stomatitis areata migrans, unlike its analogue on the tongue, migratory
      glossitis, is not easily recognized and is so uncommon and varied in appearance
      that it may escape definitive diagnosis. It may be so puzzling to the clinician
      that the patient's credibility may be questioned. A detailed report of a case is
      presented in which an atypical migratory stomatitis went undiagnosed. Bizarre
      patient behavior followed in the form of self-inflicted injury (Munchausen
      syndrome) as the patient attempted to convince the care providers of the true
      existence of lesions in order to maintain their interest and to obtain relief
      from discomfort.

PMID- 8521106
TI  - Lymphomas of the oral soft tissues are not preferentially associated with latent
      or replicative Epstein-Barr virus.
AB  - OBJECTIVES: Epstein-Barr virus is periodically shed in the saliva of persons
      infected by the virus. Epstein-Barr virus has been implicated in the pathogenesis
      of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high
      grade subtypes represent the majority of lymphomas that arise in oral soft
      tissues, we hypothesized that Epstein-Barr virus might be preferentially
      associated with oral lymphomas. STUDY DESIGN: A series of 34 oral lymphomas were
      diagnosed according to the revised European-American classification scheme. They
      were examined for the presence of latent Epstein-Barr virus by EBER1 in situ
      hybridization and for expression of the Epstein-Barr virus replicative protein,
      BZLF1, by immunohistochemistry. RESULTS: Epstein-Barr virus EBER1 transcripts
      were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas
      and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The
      Epstein-Barr virus-containing lymphomas were all high-grade histologic subtypes,
      that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast,
      Epstein-Barr virus was not detected in any of five low-grade oral lymphomas. In
      the single case of T-cell lymphoma in this study, EBER1 was expressed in the
      tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1
      expression, was identified in rare lymphoma cells in only four cases. This rate
      of viral replication was not higher than what has been reported in lymphomas
      arising at other anatomic sites. Although one of our lymphomas arose at a site of
      previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr
      virus replication predisposed to development or persistence of oral lymphomas.
      CONCLUSIONS: These data suggest that even though Epstein-Barr virus is frequently
      found in oral secretions, neither latent nor replicative Epstein-Barr virus is
      present more commonly in oral lymphomas than in lymphomas arising in other
      anatomic sites, when controlling for immunodeficiency status.

PMID- 8521107
TI  - Adverse effects of mouthwash use. A review.
AB  - Many persons use mouthrinses as a part of their routine oral hygiene. Although
      rinses impart some benefits to users, improper use of mouthrinses may result in
      various side effects. This paper reviews the adverse effects of mouthwash use as
      reported in the English-language literature.

PMID- 8521108
TI  - Estrogen and progesterone receptors in salivary gland adenoid cystic carcinoma.
AB  - Adenoid cystic carcinomas of salivary glands occur more frequently in women and
      bear remarkable similarity to adenoid cystic carcinomas of the breast. In
      addition, breast carcinomas express estrogen and progesterone receptors that
      impact prognostic significance. This suggests a possible role for sex steroid
      hormones in the development and progression of salivary gland adenoid cystic
      carcinoma. On this basis, 12 samples of formalin-fixed, paraffin-embedded
      salivary gland adenoid cystic carcinomas and 12 samples of normal salivary gland
      tissue were immunohistochemically evaluated for estrogen and progesterone
      receptor protein expression. Estrogen receptors were not detected in either
      group; however, a significantly higher progesterone receptor level was evident in
      the neoplastic group compared with normal tissue (p < 0.01). These data confirm
      the presence of progesterone receptors within normal and neoplastic salivary
      gland tissue. Progesterone receptor expression may be of possible prognostic and
      therapeutic value in some cases of adenoid cystic carcinoma.

PMID- 8521109
TI  - Desmoplastic trichoepithelioma of the upper lip. A case report with histochemical
      features and observations on its histogenesis.
AB  - A case of desmoplastic trichoepithelioma of the upper lip investigated by
      histochemistry and immunocytochemistry is presented. There was histologic
      suggestion of cytoplasmic vacuolation that does not appear to have been
      previously described. Histochemical examination indicated the presence of
      glycogen within tumor cells and a reparative-type stroma. Immunocytochemical
      examination revealed variable reactivity for high molecular weight cytokeratin
      and colonization by Langerhans' cells. The observations suggest a follicular and
      sudoriferous differentiation for desmoplastic trichoepithelioma and hence an
      origin from a pluripotential adnexal keratinocyte.

PMID- 8521110
TI  - Effect of four vehicles on the pH of calcium hydroxide and the release of calcium
      ion.
AB  - Nonsetting calcium hydroxide pastes are commonly used in endodontic practice. The
      desired therapeutic effect of such a paste is in part dependent on the
      dissociation of calcium hydroxide into hydroxy ion and calcium ion. This in turn
      is influenced by the vehicle used to make the paste. This investigation attempts
      to quantitatively estimate the release of hydroxyl ion and calcium ion from
      pastes made by using distilled water, normal saline solution, camphorated
      monochlorophenol and also an experimental vehicle, propylene glycol. The results
      of this study indicate that propylene glycol induces the most favorable release
      characteristics of the two ionic species.

PMID- 8521111
TI  - Misdiagnosis and mismanagement of a nasopalatine duct cyst and its corrective
      therapy. A case report.
AB  - A case is presented in which a nasopalatine duct cyst was misdiagnosed. Its
      subsequent mismanagement was further compounded with improper endodontic therapy.
      It was finally managed by corrective endodontic and surgical therapy.

PMID- 8521112
TI  - Future trends in dental radiology.
AB  - Direct digital dental radiographic systems offer the potential to radically
      change the way dentists diagnose and treat dental pathoses. They offer
      instantaneous availability of radiographs, markedly lower patient radiation
      exposure, and the elimination of developing chemicals and developing equipment.
      The storage of dental radiographs as digital data permits their transmittal over
      phone lines facilitating phone consultations and may someday allow expedited
      authorization of treatment plans by dental insurance companies. With the use of
      digital subtraction radiology the dental practitioner will be able to diagnose
      periodontal disease progression and dental caries progression long before current
      techniques can detect a change. With tuned aperture computed tomography, the
      owner of a filmless digital system can make tomographic radiographs that allow
      the visualization of slices through areas of interest without having to buy
      additional hardware. Computer-aided diagnosis will facilitate the detection of
      proximal dental caries and osteoporosis, and may someday allow automated tracing
      of cephalometric radiographs.

PMID- 8521113
TI  - Effect of logarithmic contrast enhancement on subtraction images.
AB  - The aim of this study was to analyze logarithmic contrast enhancement as compared
      with regular digital subtraction and to consider effects of image texture and
      observer experience. Radiographs of three different textures, including computer
      stimulated lesions of various sizes and densities, were subtracted from
      radiographs taken before lesions were placed. Logarithmically enhanced and
      regular subtraction images were put in random order with an equal number of
      nonlesion subtraction images to form a series of 300 images. Twenty subjects were
      asked to decide on a 5-point confidence scale whether a lesion was present. Plain
      texture images were diagnosed significantly better than bone and enamel images.
      Logarithmic contrast enhancement had a positive effect on plain texture images.
      There was no significant experience effect. In the student group, however, there
      was a significant difference between the two subtraction methods. Overall,
      logarithmic contrast enhancement provided better diagnostic validity than regular
      subtraction. Logarithmically enhanced subtraction radiography seems to be a
      promising method for images with low-contrast gradients.

PMID- 8521114
TI  - Radiographic maxillary sinus findings in the elderly.
AB  - The prevalence of radiographic maxillary sinus findings in 293 elderly subjects
      (76, 81, and 86 years old) were investigated with the use of panoramic
      radiography: 124 subjects were edentulous in both jaws, 167 had an edentulous
      maxilla, and 169 had at least one natural tooth left. Mucous cysts or diffuse
      mucosal thickenings were found in 12% of the subjects. Of the mucosal
      thickenings, 70% were found in subjects with a dentate upper jaw (p < 0.05),
      suggesting an odontogenic origin for that proportion (40%) exceeding the
      prevalence in subjects edentulous in the maxilla. That the prevalence of mucous
      cysts was 5% both in subjects with a dentate upper jaw and in those with a
      edentulous upper jaw suggests nonodontogenic causes.

PMID- 8521115
TI  - Practice parameters for allergy diagnostic testing. Joint Task Force on Practice
      Parameters for the Diagnosis and Treatment of Asthma. The American Academy of
      Allergy, Asthma and Immunology and the American College of Allergy, Asthma and
      Immunology.

PMID- 8521116
TI  - The association between oral leukoplakia and use of tobacco, alcohol and khat
      based on relative risks assessment in Kenya.
AB  - A case-control study was conducted to determine the significance of tobacco,
      alcohol and khat (Catha edulis) chewing habits in the development of oral
      leukoplakia among Kenyans aged 15 yr and over. In a house-to-house survey, 85
      cases and 141 controls matched for sex, age and cluster origin was identified and
      compared for these risk factors. Smoking unprocessed tobacco (Kiraiku) with a
      relative risk (RR) of 10.0 (95% confidence interval (CI) = 2.9-38.4) and smoking
      cigarettes (RR = 8.4; 95% CI = 4.1-17.4) were the most significant factors. While
      the RR associated with smoking cigarettes alone was 4.5 (95% CI = 1.9-10.8),
      smoking of both products (RR = 15.2) suggested probable synergy or additive
      effects. Oral leukoplakia in 18 cases could not be attributed to smoking tobacco.
      Commercial beer, wines and spirits were relatively weak, but statistically
      significant, risk factors. Traditional beer, khat and chilies were not
      significantly associated with oral leukoplakia.

PMID- 8521117
TI  - Oral health in Latvian 15-year-olds.
AB  - Oral hygiene, caries and periodontal conditions were assessed in a representative
      sample of 15-year-old Latvian schoolchildren, comprising 506 subjects. Caries,
      diagnosed on the cavity level, was detected in 97.6% of the population. The mean
      DMFT and DMFS were 8.1 and 14.1, respectively. Although 91% of the children had
      had restorative treatment, the D component accounted on average for 33% of the
      DMFS score. Visible dental plaque was found in 98.4% of the children; in a
      majority (88%) abundant plaque deposits were recorded. Community Periodontal
      Index of Treatment Needs (CPITN) was assessed by standard WHO methods. Deviation
      from periodontal health was observed in 90.7% of the children. Calculus was
      recorded in 26.1% and gingival pockets in 25.9% of the sample. Additionally,
      38.7% of the children had gingival bleeding. The mean number of sextants with
      healthy periodontal conditions was 2.5. Calculus and pocketing averaged 0.6 and
      0.4 sextants, respectively. Attachment loss, recorded in 11.7% of the subjects,
      did not exceed 3 mm. The results showed high caries prevalence, considerable need
      for treatment and virtual absence of oral hygiene.

PMID- 8521118
TI  - Salivary and serum IgA antigliadin antibodies in dermatitis herpetiformis.
AB  - Serum IgA class antigliadin antibodies (IgA-AGA) are increased in untreated
      patients with coeliac disease and dermatitis herpetiformis (DH), and it has been
      suggested that salivary IgA-AGA measurements could be used as a non-invasive
      screening test for gluten-sensitive enteropathy. In the present study salivary
      and serum IgA-AGA were measured by an ELISA test in 10 untreated patients with
      DH. The results were compared to IgA-AGA levels in nine patients with DH on a
      long-term gluten-free diet (GFD) and in 20 healthy control subjects on an
      ordinary diet. The mean serum but not salivary IgA-AGA concentrations were
      significantly higher in the untreated than in the patients with DH on a long-term
      GFD. When the 10 untreated patients with DH adhered to a GFD for 3 months, the
      rash disappeared and the mean serum IgA-AGA decreased to normal levels, but no
      change was found in the mean salivary IgA-AGA concentration. These results show
      that serum but not salivary IgA-AGA measurements are suitable for monitoring GFD
      treatment in patients with DH. The discrepancy between the serum and salivary IgA
      AGA concentrations suggests that systemic and salivary IgA-AGA responses are
      controlled separately.

PMID- 8521119
TI  - Sleeping positions and dental arch dimensions in children with suspected
      obstructive sleep apnea syndrome.
AB  - The present paper analyzed the association between children's sleeping positions
      and dental arch morphology. The sleeping patterns of 27 children, aged 3 to 10
      yr, suspected of having the obstructive sleep apnea syndrome (OSAS) were studied
      by polysomnography (PSG) and videotape recordings under laboratory conditions.
      The PSG recordings were used to calculate the apnea index (AI) and the relative
      time spent sleeping on the back, and the videotapes to categorize distinctly
      different sleep and head postures. Plaster casts were made for the assessment of
      dental arch morphology. Sleeping predominantly on one's back, was associated with
      a reduced maxillary intercanine width, while prolonged head extension during
      sleep correlated inversely with the overjet. The subjects with the highest AI
      scores (> 4) had larger dental arches. We suggest that sleeping on the back
      causes a more posterior tongue position, reducing its moulding effect on the
      anterior dental arch. As nasopharyngeal airway obstruction in OSAS-patients might
      trigger an anterior tongue position to secure a free airway passage, there will
      be increased lingual pressure on the dental arches, leading to their dimensional
      increase.

PMID- 8521120
TI  - Spatial and temporal repair patterns of orthodontically induced surface
      resorption patches.
AB  - Root resorption appears to be an inevitable sequel to orthodontic tooth movement,
      occurring either apically or along surfaces in and around the pressure zones.
      However, there is uncertainty as to the location of initial cementum repair in
      resorbed areas as well as the time of onset of repair. The aim of the present
      study was to map the spatial and temporal patterns of cementum repair in
      orthodontically induced areas of surface resorption following maxillary
      expansion. Two spatial patterns of repair of orthodontic surface resorption
      patches were observed with cementum deposition proceeding either from the
      periphery or starting somewhere in the center of the resorbing areas, although
      the deposition starting centrally was argued to be artifactual. Furthermore,
      onset of reparative cementum mineralization appeared to follow within 2 wk after
      release of the force, involving initially only acellular cementum formation.
      However, the pattern of formation changed gradually, favouring a slow deposition
      of cellular cementum at more advanced stages of healing.

PMID- 8521121
TI  - The effects of low level laser treatment on recovery of nerve conduction and
      motor function after compression injury in the rat sciatic nerve.
AB  - An animal study is presented examining the effect of low level laser (LLL)
      treatment on nerve regeneration following axonotmesis. Twenty animals received a
      standardised injury to the right sciatic nerve using a time, load and length
      sequence (10 min, 150 N, 5 mm) known to cause extensive axonal degeneration of
      the rat sciatic nerve. The LLL treatment was administered using a hand-held laser
      probe in light contact with the skin on the dorsal aspect of the hind leg
      overlying the site of the axonotmesis injury to the sciatic nerve. A group of 10
      animals were treated with 6J of LLL (GaAlAs 830 nm) daily for a period of 28 d.
      Ten more animals were treated daily with a sham exposure setting and served as
      controls. Nerve function was assessed by a recognised method of walking tract
      print analysis; the "Sciatic Functional Index" (SFI), and nerve regeneration was
      assessed by recording the evoked compound action potentials (cAP) in the common
      peroneal nerve. At 21 d post-injury, the laser-treated group had a significantly
      lower median SFI than the sham laser-treated group, indicating that the real
      laser treatment had improved functional recovery in the nerve. However, no
      differences were found between the evoked cAP parameters that were measured in
      the laser-treated and sham laser-treated groups. Histological examination
      reiterated the lack of difference between the two groups. Consequently, the
      effects of LLL on recovery must have occurred more peripherally to the point
      measured.

PMID- 8521122
TI  - Effects of mouthrinses with chlorhexidine and zinc ions combined with fluoride on
      the viability and glycolytic activity of dental plaque.
AB  - Inhibition of plaque acidogenicity by a mouthrinse with chlorhexidine (CHX) or
      zinc ions has been ascribed to a prolonged bacteriostasis due to substantive
      properties of the agents. The present aim was to study the effects of mouthrinses
      with CHX and Zn ions combined with fluoride on the viability and glycolytic
      activity of dental plaque in order to assess the bacteriostatic versus possible
      bactericidal effects. Following 2 d of plaque accumulation, 4 groups of 10
      students rinsed with either 12 mM NaF (F), 0.55 mM CHX diacetate+F (F-CHX), 10 mM
      Zn acetate+F (F-Zn), or with the three agents in combination (F-CHX-Zn). Plaque
      samples were collected before and 90 min after mouthrinsing. Thereafter, the in
      vivo plaque pH response to sucrose was monitored in each student using touch
      microelectrodes. F-CHX and F-CHX-Zn reduced the in vivo pH fall significantly as
      compared with F, whereas F-Zn exerted a non-significant inhibition. Pooled pre-
      and post-rinse plaque samples were used to measure the pH fall during
      fermentation of [14C]-glucose, and the glycolytic profiles were analyzed by HPLC.
      Bacterial viability was assessed by counting the colony-forming units (CFU). All
      mouthrinses except F reduced glucose consumption and acid formation and thus the
      pH fall. F-CHX reduced the CFU equal to the reduction of glucose consumption,
      indicating that inhibition of plaque acidogenicity was due to a bactericidal
      rather than a bacteriostatic effect. F and F-Zn did not reduce the CFU, thus F-Zn
      decreased glucose metabolism without affecting plaque viability. F-CHX-Zn reduced
      both the CFU and glucose metabolism of surviving plaque microorganisms.

PMID- 8521123
TI  - Tissue reaction to gutta-percha particles of various sizes when implanted
      subcutaneously in guinea pigs.
AB  - Tissue reaction to gutta-percha was studied using subcutaneously implanted Teflon
      cages in guinea pigs. Gutta-percha was tested in three forms: (i) as large
      particles prepared by dividing gutta-percha cones into pieces, (ii) as fine
      particles prepared by ball-milling of gutta-percha, and (iii) as particles
      produced by dissolving gutta-percha in rosin-chloroform. Gutta-percha evoked two
      distinct types of tissue response. The large pieces were well encapsulated and
      the surrounding tissue was free of inflammation. The fine particles evoked an
      intense, localized tissue response, characterized by the presence of macrophages
      and multinucleated giant cells. The rosin-chloroform treated gutta-percha induced
      a similar tissue reaction to that observed with the fine particles of gutta
      percha. In addition, cell remnants were present in association with the material,
      which indicates an initial toxicity to rosin-chloroform treated gutta-percha.
      These results show that the size and surface character of gutta-percha can
      determine the type of tissue reaction to the material. The accumulation of
      macrophages around gutta-percha may be an important factor in the impairment of
      healing of periapical lesions when teeth are root filled with excess material.

PMID- 8521124
TI  - Influence of light intensity on polymerization shrinkage and integrity of
      restoration-cavity interface.
AB  - The results of this study showed that the use of high intensity curing light
      units negatively affected the integrity of the restoration-cavity interface in
      class V restorations This is explained by the high reaction rates of light curing
      resin composites. The interfacial integrity was better preserved with low light
      intensity as it extends the visco-elastic stage of the setting materials, thereby
      moderating the setting stress development. The ultimate polymerization shrinkages
      for both conditions were equal, which suggested equal degrees of conversion and
      thus equal material properties. The results may alleviate the trend in using
      higher intensity light curing units and in particular the development of units
      with laser beams in an attempt to further increase conversion rates.

PMID- 8521125
TI  - Casting of Ti-6Al-4V alloy compared with pure Ti in an Ar-arc casting machine.
AB  - Dental prostheses of Ti are normally cast in pure Ti. Some appliances, however,
      require higher yield strength. Casting of Ti alloys is of interest in such cases.
      The objective of the present work was to study the quality of castings made of Ti
      6Al-4V compared with those made of pure Ti. Casting was made into a mold kept at
      room temperature using a MgO-Al2O3 investment. A standardized five-unit bridge
      was cast, consisting of two cylindrical crowns with sharp margins and three
      pontics. The overall mold filling was satisfactory. The margins of the casting
      alloys were, however, more rugged and incomplete than those of pure Ti. The most
      likely reason for this difference is the increased formation of dendrites in the
      alloy and thus more resistance to fluid flow. Furthermore, the sprue of the alloy
      was also found to contain some spherical, internal pores. Such pores were rare in
      the pure Ti castings. The surface reactions were found to be minimal for both of
      the materials. Increased casting deficiencies observed in the cast bridges of the
      Ti-6Al-4V alloy, compared with pure Ti, were: 1) the margins of the crowns in the
      bridge were less complete and 2) there was a tendency to an increased internal
      porosity, particularly in the sprues.

PMID- 8521126
TI  - Factor analysis and reduction of a Fear Survey Schedule among dental phobic
      patients.
AB  - A fear survey instrument, based on the Fear Survey Schedule-II and five
      additional fear items, was administered to 109 patients (70 women and 39 men) on
      a waiting list at a specialized dental fear clinic. The fear survey was analyzed
      to identify its factorial structure. Five fear factors, explaining 54% of the
      total variance, were identified concerning areas of "illness and death",
      "failures and embarrassment", "social situations", "physical injuries", and
      "animals and natural phenomena". An ad hoc reduction of items was carried out to
      form a shorter, more practical to use questionnaire, which resulted in factors of
      four or five items with loadings greater than 0.50. The factors intercorrelated
      significantly (rp varying between 0.33 and 0.59) and "illness and death"
      correlated highly with "physical injuries" (rp = 0.59) and "animals and natural
      phenomena" (rp = 0.56), while "failures and embarrassment" correlated highly to
      "social situations" (rp = 0.54). Statistically significant, but generally lower
      correlations were found between each factor and the dental fear measures. The
      highest correlations were found between fear of "physical injuries" and dental
      fear. There was also a high and significant correlation between sex and fear of
      "animals and natural phenomena".

PMID- 8521127
TI  - Multivariate analysis of fears in dental phobic patients according to a reduced
      FSS-II scale.
AB  - This study analyzed and assessed dimensions of a questionnaire developed to
      measure general fears and phobias. A previous factor analysis among 109 dental
      phobics had revealed a five-factor structure with 22 items and an explained total
      variance of 54%. The present study analyzed the same material using a
      multivariate statistical procedure (LISREL) to reveal structural latent
      variables. The LISREL analysis, based on the correlation matrix, yielded a chi
      square of 216.6 with 195 degrees of freedom (P = 0.138) and showed a model with
      seven latent variables. One was a general fear factor correlated to all 22 items.
      The other six factors concerned "Illness & Death" (5 items), "Failures &
      Embarrassment" (5 items), "Social situations" (5 items), "Physical injuries" (4
      items), "Animals & Natural phenomena" (4 items). One item (opposite sex) was
      included in both "Failures & Embarrassment" and "Social situations". The last
      factor, "Social interaction", combined all the items in "Failures &
      Embarrassment" and "Social situations" (9 items). In conclusion, this
      multivariate statistical analysis (LISREL) revealed and confirmed a factor
      structure similar to our previous study, but added two important dimensions not
      shown with a traditional factor analysis. This reduced FSS-II version measures
      general fears and phobias and may be used on a routine clinical basis as well as
      in dental phobia research.

PMID- 8521128
TI  - T1c cancer: what is it?
AB  - With the advent of more-routine prostate-specific antigen (PSA) blood testing,
      many more patients are being identified in whom the only clinical sign of their
      underlying disease is an elevated PSA level. Most evidence to date suggests that
      such patients do harbor clinically significant cancers and thus should be treated
      in a fashion similar to patients with T1b, T2a, and T2b disease.

PMID- 8521129
TI  - Preoperative estimate of extent of disease in T1c: how well can we predict?
AB  - Serum prostate-specific antigen testing and systematic ultrasound-guided biopsy
      has improved our ability to diagnose low-stage, nonpalpable prostate cancer. With
      improvement of diagnostic sensitivity, the risk of finding clinically
      insignificant or "latent" prostate cancer has likewise increased. The potential
      morbidity and expense of overdiagnosing and treating latent prostate cancer has
      necessitated the search for better methods of determining tumor extent and
      significance. This information may then be used for development of individual
      treatment strategies. Serum prostate-specific antigen level, prostate-specific
      antigen density, and characterization of biopsy tissue appear to be reasonably
      accurate methods of estimating tumor extent.

PMID- 8521130
TI  - Are T1c tumors different from incidental tumors found at autopsy? The risk and
      reality of overdetection.
AB  - The wisdom governing contemporary prostate cancer screening or early detection
      programs continues to be scrutinized. Although the mild increase in death rate
      speaks for itself, the enormously disparate and accelerating incidence rates have
      attained widespread attention. The abrupt recent downstage migration suggests
      that T1c lesions may be the arguable culprit. For more than 50 years, we have
      known that incidental prostate cancers found at autopsy are very common. Given
      these odds, it is not surprising that these cancers will be found antemortem.
      Mathematical models correctly predict the discovery of small-volume cancers with
      multiple biopsies. Although there are some anticipated differences between T1c
      and incidental tumors found at autopsy, the overlap is predictably large,
      suggesting that a conservative answer to the question posed in the title is:
      Maybe yes, but often not much.

PMID- 8521131
TI  - Counseling patients about therapy for localized prostate cancer.
AB  - The major therapeutic approaches to localized prostate cancer are radical
      prostatectomy, external beam radiation therapy, and surveillance or observation.
      The appropriate treatment for a specific patient depends on tumor stage, grade,
      and prostate-specific antigen (PSA) level, as well as on patient age, medical
      status, life expectancy, and patient preference. A patient with localized
      prostate cancer should understand the nature of these therapeutic approaches and
      their possible complications. In the absence of good long-term outcome data,
      patient preference is a significant factor.

PMID- 8521132
TI  - Radiotherapy of T1c prostate cancer.
AB  - With a 10-year local control rate of 85% to 100% and a low complication rate,
      radiotherapy is an effective treatment option for T1c prostate cancer.
      Controversial topics, such as treatment volumes and dose-response, are critically
      reviewed. New investigational approaches will be discussed.

PMID- 8521133
TI  - Cost-efficient radical prostatectomy.
AB  - Radical retropubic prostatectomy is an easily standardized procedure with
      reproducible outcomes. Care has been standardized at our institution through the
      use of a collaborative care approach that defines the optimal care and outcomes
      for the ideal patient on a daily basis. This approach is based on an objective
      evaluation of the available medical literature. With this program, hospital
      charges have been reduced by 41% and hospital stay has been reduced to 2.9 days.
      Surgical outcomes have been excellent with low morbidity rates and excellent
      patient acceptance. Collaborative care programs for health care provide a
      comprehensive approach that allows for the delivery of cost-efficient care, which
      is supportive of the patient and allows continual refinement in care based on
      objective analysis of outcomes.

PMID- 8521134
TI  - Current results and patient selection for nerve-sparing radical retropubic
      prostatectomy.
AB  - The anatomical radical retropubic prostatectomy currently may be performed with
      low morbidity and mortality. The nerve-sparing aspect of the anatomical radical
      retropubic prostatectomy has allowed preservation of potency in the majority of
      men with localized prostate cancer. Overall potency rates of up to 71% may be
      achieved without compromising the complete eradication of cancer. Prostate cancer
      control with nerve-sparing surgery is similar to that reported for the standard
      radical retropubic prostatectomy. Inaccurate clinical staging of prostate cancer
      and the inability to determine tumor involvement of the neurovascular bundle have
      made it difficult to decide with certainty preoperatively which patients should
      undergo preservation versus wide excision of the neurovascular bundle. Some of
      the controversies that may determine utility of nerve-sparing radical
      prostatectomy include the impact of prostate cancer capsular penetration and
      positive surgical margins on tumor progression and patient survival. The
      selection of the ideal patient who has clinically localized prostate cancer for
      nerve-sparing radical prostatectomy has been improved by using as guidelines such
      preoperative factors as serum prostate-specific antigen tumor grade and the
      presence of perineural invasion on biopsy, and by using tumor location and volume
      to help predict true pathological stage. Other preoperative studies including
      transrectal ultrasound, computed tomography, and magnetic resonance imaging are
      generally not helpful.

PMID- 8521135
TI  - Management of erectile dysfunction after radical prostatectomy.
AB  - Sexual rehabilitation is a vital component of the overall care of the prostate
      cancer patient and contributes significantly to the subsequent quality of life.
      Despite the development of and refinements in the anatomic approach to radical
      prostatectomy, there will continue to be a large pool of patients with erectile
      dysfunction after surgery. Although cancer control is always of primary
      importance, potency is often a consideration of great concern to patients when
      deciding between the various treatment options for clinically localized prostate
      cancer. Preoperative counseling informing the patient that erectile dysfunction
      can be successfully managed in most cases with therapy tailored to the goals and
      expectations of both the patient and the partner is essential. This article
      presents an overview of the approach to and management of the patient with
      erectile dysfunction after radical prostatectomy focusing on three main
      therapies: vacuum constriction devices, intravernoal injections, and prosthetic
      penile implants.

PMID- 8521136
TI  - Prevention and treatment of incontinence after radical prostatectomy.
AB  - Postoperative complications after radical prostatectomy have only recently been
      studied in a formal prospective manner. A survey of existing literature yields
      widely disparate rates of postoperative incontinence. Classically, about 5% of
      patients were believed to be incontinent. More recent studies that involve
      patient questionnaires and a specific continence history indicate that nearly 30%
      of patients experience some urinary leakage with activity. Evolving new operative
      techniques such as modified apical dissection and construction of a tubularized
      neourethra have potential to improve continence rates considerably. Patients who
      do experience urinary incontinence should be offered appropriate evaluation and
      treatment. In addition to cystourethroscopy, all patients should undergo
      cystometry and Valsalva leak-point testing to differentiate sphincteric
      dysfunction from detrusor instability. Injection of bovine cross-linked collagen
      into the preexternal sphincter zone or implantation of the artificial urinary
      sphincter are options for treatment of intrinsic sphincter dysfunction. Detrusor
      instability is best treated with pharmacotherapy. This article discusses the
      details of prevention, evaluation, and treatment of postprostatectomy
      incontinence.

PMID- 8521137
TI  - Stage T1c prostate cancer: perspectives on clinical management.
AB  - Nonpalpable prostate cancer, detected on a biopsy sample and prompted by an
      elevated prostate-specific antigen level, has become one of the most common
      presentations of the disease. The clinical significance of these cancers has been
      debated, but pathologic examination has shown a substantial tumor volume in most
      patients. On the other hand, a tumor is confined within the surgical margins in
      some 80% of men undergoing radical prostatectomy for T1c cancers. Overall, then,
      most T1c prostate cancers meet the desired selection criteria for radical
      prostatectomy, which include a tumor of clinical significance, yet one which can
      be totally excised surgically.

PMID- 8521138
TI  - Prepubertal castration alters the phenotypic profile of adult rat thymocytes.
AB  - To assess the gonadal influence on the maturation of the thymus, rats were
      orchidectomized at different periods critical for programming of both gonadal and
      immune functions, and the composition of the intrathymic thymocyte population was
      determined in adults by flow cytometric analysis of the surface phenotype. The
      relative proportion of thymocytes expressing CD4, CD8 and T cell receptor
      (TCR)alpha beta was measured in the adult rats castrated at 1, 7 and 30 days.
      Castration performed at postnatal day 1 did not significantly affect expression
      of these molecules. However, in rats subjected to the surgery at day 7, a
      significant decrease in the proportion of CD4+CD8+ double-positive cells was
      found, in parallel with a proportional increase in the percentage of CD4+CD8-
      single-positive (SP) cells. In rats castrated at age 30 days, in addition to
      these changes, a small but significant increase in the percentage of CD4-CD8+ SP
      thymocytes was measured. Castration performed at age 7 and 30 days also caused an
      enrichment in the thymocyte population expressing TCR alpha beta, probably
      related to the increase of CD4+CD8- SP cells (7 days) and both CD4+CD8- and CD4
      CD8+ SP cells (30 days). The total yield of thymocytes was increased in all
      experimental groups. We conclude that T cell maturation sequences in the adult
      thymus are altered if gonadal influence is removed during certain stages of
      thymus development.

PMID- 8521139
TI  - Cloning and nucleotide sequencing of rat lymphocyte growth hormone cDNA.
AB  - The messenger RNA for rat growth hormone (GH) was isolated from rat spleen
      lymphocytes and cloned as a cDNA after PCR. Four clones, including part of the
      prehormone sequence and the full-length mature GH sequence, were obtained and
      sequenced. The sequence data revealed that rat lymphocyte GH was identical to
      that reported for pituitary GH. The results do not support the expression by
      alternate splicing of the 20-kD variant described in the pituitary. We also
      cloned the promoter of lymphocyte GH and analyzed its nucleotide sequence
      including 300 base pairs of the 5'-flanking region. The promoter sequence we
      obtained did not exactly match that reported in the literature because of reading
      compressions on the gel. However, parellel sequencing of thymus, spleen and
      pituitary GH promoter sequences gave identical patterns of compressions in the
      gel. The results suggest that the sequence in all the tissues was the same.
      Collectively, these studies demonstrate that lymphocytes express authentic GH
      mRNA and suggest that GH gene expression may be regulated in immune tissue by
      similar transcriptional factors to those described in the pituitary.

PMID- 8521140
TI  - Expression of T cell receptor gamma delta antigens in human brain tissue.
AB  - The human gamma delta T cell receptor (TCR) is normally expressed on lymphoid
      tissue. Since expression of different molecules of the T cell system has been
      described for human brain cells, we examined the expression of CD4 and TCR gamma
      delta antigens with a panel of various anti-gamma delta TCR monoclonal antibodies
      (mAbs) and an anti-CD4 mAb using immunohistochemistry on different regions of
      frozen human postmortem tissue from five different brains. We could confirm the
      expression of CD4 antigens. gamma delta TCR expression on brain tissue was found
      in different regions of the brain by immunohistochemistry. Double staining with
      anti-gamma delta TCR and antineuronal enolase (NSE) mAbs showed that gamma delta
      TCR+ cells were not stained by anti-NSE, although they were sometimes located
      near neurons and showed dendritic forms; they are possibly tissue-resident gamma
      delta T cells, as described in the skin. Polymerase chain reaction analysis using
      a highly sensitive primer sequence against the constant-region delta sequence
      supports, combined with immunohistochemistry findings, the notion that the gamma
      delta TCR is expressed in human brain.

PMID- 8521141
TI  - Induction of interleukin-1 beta mRNA and enkephalin mRNA in the rat adrenal gland
      by lipopolysaccharides studied by in situ hybridization histochemistry.
AB  - Interleukin-1 is a macrophage-derived cytokine, which can also be synthesized in
      other cell types. It has been shown to exert several activities in the nervous
      and endocrine system, including a potent activating effect on the hypothalamo
      pituitary-adrenal axis. High levels of interleukin-1 have previously been found
      in the adrenal gland. The effect of bacterial lipopolysaccharides (2.0 mg/kg) on
      interleukin-1 beta mRNA was studied in the rat adrenal gland by in situ
      hybridization histochemistry using a synthetic oligonucleotide probe. A transient
      induction was observed, with the strongest hybridization signal seen after 1.5 h
      and subsequent decrease to near basal levels at 3 h. Similarly, the effect of
      lipopolysaccharides on preproenkephalin A mRNA expression in the adrenal gland
      was analyzed. Preproenkephalin A is a precursor for methionine-enkephalin, a
      neuropeptide known to be produced in the chromaffin cells, and also known to
      affect immunological functions. A low level of preproenkephalin A mRNA was seen
      in the adrenal medulla in animals injected with saline and 0.5 h after
      lipopolysaccharide administration. A small, but distinct increase in
      hybridization signal appeared at 1.5 h and a marked increased was observed at 3 h
      after administration of lipopolysaccharides. In addition to the different
      kinetics of expression after LPS administration, the two mRNA species showed a
      somewhat different morphological distribution in that IL-1 beta mRNA could be
      seen in both adrenal medulla and cortex, whereas preproenkephalin A expression
      was confined to the adrenal medulla.

PMID- 8521142
TI  - Tumor necrosis factor-alpha in the dorsal vagal complex suppresses gastric
      motility.
AB  - Gastric hypomotility, loss of appetite, nausea, and vomiting frequently accompany
      critical infectious illness, radiation sickness, and carcinogenesis. The present
      studies examined the possibility that the pro-inflammatory cytokine, tumor
      necrosis factor-alpha (TNF-alpha), may be responsible for provoking some of these
      autonomic signs associated with illness. Gastric motility of urethane
      anesthetized rats was prestimulated with intracisternal applications of
      thyrotropin-releasing hormone (TRH), a peptide known to activate parasympathetic
      vagal excitatory pathways to the stomach. Microinjection of TNF-alpha (as low as
      0.02 fmol) directly into the dorsal vagal comples (DVC) suppressed TRH-stimulated
      gastric motility for prolonged periods of time. Duration of suppression ranged
      from 5 min to more than an hour, dependent on both the dose of TNF-alpha and
      accuracy of placement of the microinjection within the DVC. This suppression
      demonstrated a dose-dependent effect of TNF-alpha that required an intact vagal
      pathway. These studies indicate that TNF-alpha may represent a unique cytokine
      'afferent' signal which directly regulates the excitability of vago-vagal reflex
      circuits resulting in altered gastric motility during disease states.

PMID- 8521143
TI  - Brain interleukin-1 is involved in generation of the serum suppressive factor
      induced by restraint stress in mice.
AB  - Our previous work showed that a factor (a protein with a high molecular weight)
      in serum was induced by restraint stress in mice and rats, and suppressed
      lymphocyte proliferation induced by concanavalin A. It was also found that the
      generation of the serum suppressive factor was under the control of the central
      nervous system. The present work was designed to investigate the role of
      interleukin-1 (IL-1) in the brain in the serum suppressive factor. IL-1 receptor
      antagonist (IL-1ra) was injected intracerebroventricularly in mice and the
      generation of the serum suppressive factor was found to be significantly
      decreased in a dose-dependent manner. When the dose of IL-1ra reached 5
      micrograms, the generation of the suppressive factor was almost totally
      abolished. Intracerebroventricular injection of IL-1 beta (1.0 pg) enhanced the
      generation of the suppressive factor. Taken together, these results indicate the
      involvement of IL-1 in the brain in mediating generation of the suppressive
      factor.

PMID- 8521144
TI  - Involvement of oxytocin and cholecystokinin-8 in interleukin-1 beta-induced
      adrenocorticotropin secretion in the rat.
AB  - It is well established that corticotropin-releasing hormone (CRH) is a principal
      neuropeptide which mediates the adrenocorticotropic hormone (ACTH) secretory
      response to interleukin (IL)-1 in the rat. It has recently been suggested that
      besides CRH, arginine vasopressin may also play a stimulatory role in IL-1
      induced ACTH secretion. However, it remains to be elucidated whether other
      neuropeptides possessing an ACTH-releasing activity are involved in this
      neuroendocrine event. Therefore, in this study, we examined possible roles for
      oxytocin (OT) and cholecystokinin (CCK)-8 in the IL-1-induced ACTH response,
      utilizing the technique of immunoneutralization of these peptides. For
      comparison, we examined the effect of CRH immunoneutralization as well. Human
      recombinant IL-1 beta (50 ng) was given intracerebroventricularly (to the 3rd
      ventricle) to freely moving male rats 15 min after injecting specific antiserum
      against CRH, OT, or CCK-8, or normal rabbit serum (control) via the same route.
      As expected, anti-CRH antibody significantly suppressed the ACTH response to IL-1
      beta. Interestingly, anti-OT antibody acted in the same manner, whereas anti-CCK
      8 antibody did not. These results suggest that in addition to CRH and arginine
      vasopressin, OT may also play a significant role in mediating the IL-1 beta
      induced ACTH secretion in the rat.

PMID- 8521145
TI  - Learned immunosuppression is associated with an increased risk of chemically
      induced tumors.
AB  - Based on the hypothesis that certain aspects of the CNS and immune system
      interact and that altered immune function affects carcinogenesis, an animal model
      was developed to examine the effects of learned immunosuppression on the
      development of a chemically induced tumor. In two experiments, we evaluated
      whether mice, for which immunosuppression was associated with a neutral
      (conditioned) stimulus, would exhibit an increased susceptibility to tumor
      development upon reexposure to the conditioned stimulus, as compared to
      nonconditioned and control animals. A taste aversion conditioning paradigm, based
      on classical conditioning techniques, was employed to suppress immune function
      using the cytotoxic and immunosuppressive drug cyclophosphamide (CY) as the
      unconditioned stimulus and consequently increase the risk of chemically induced
      tumorigenesis. CY (100 mg/kg, intraperitoneal) was paired with saccharin in the
      drinking water (0.1%) of adult female mice (CF-1). Conditioned mice were exposed
      to saccharin twice in the absence of CY, on days 4 and 7 after the first exposure
      (day 1). All mice were injected with the chemical carcinogen 9,10
      dimethylbenzanthracene (DMBA, 50 mg/kg, subcutaneous) on day 4 of conditioning.
      Two subsequent exposures to saccharin alone substantially increased the risk of
      developing DMBA-induced tumors (ranging from 83-91%), as compared to control
      animals (36%) that had not received this pairing. Mice that received all agents
      (i.e., CY, DMBA, and saccharin) in a slightly different order did not display
      elevated tumor incidence. Three separate exposures to CY also significantly
      increased the number of animals developing tumors in response to the carcinogen
      (75%). Mice were observed for at least 8 weeks after conditioning.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8521146
TI  - Physical training improves body composition of black obese 7- to 11-year-old
      girls.
AB  - We determined the effect of supervised physical training without dietary
      intervention, on body composition of obese girls. The subjects were 25 obese 7-
      to 11-year-old black girls, divided into physical training and lifestyle
      education groups which were comparable on baseline body composition; 22 girls
      finished all aspects of the study. Twelve girls engaged in aerobic training (10
      weeks, 5 days/week) while 10 engaged in weekly lifestyle discussions without
      formal physical training. Total body and regional body composition were measured
      with dual energy x-ray absorptiometry, skinfolds and circumferences. Aerobic
      fitness was measured by heart rate response to submaximal treadmill exercise. The
      physical training group attended 94% of scheduled sessions and kept their heart
      rates at an average of 163 bpm for 28 minutes/session. The lifestyle group
      attended 95% of their sessions; they remained stable in aerobic fitness and most
      body composition measurements. The physical training group showed a significant
      improvement in aerobic fitness and a significant decline of 1.4% body fat.
      Skinfold and circumference indices of fatness also declined significantly in the
      training group. We conclude that controlled physical training, without dietary
      intervention, improved the fitness and body composition of obese black girls.

PMID- 8521147
TI  - Biracial differences in physical activity and body composition among women.
AB  - Overweight among black females is almost two times as frequent as among white
      females. Genetics, caloric intake, and physical activity have been identified as
      possible explanatory factors. This study assessed the differences in physical
      activity and body composition in 76 white and 66 black adult females. Black women
      had significantly higher (p = .0001) percent body fat (32.2 +/- 7.1) than white
      women (27.7 +/- 6.5) with a similar difference in weight (4.4 kg) approaching
      significance (p = .055). Physical activity was assessed using a structured 24
      hour recall instrument. A purposive sampling design was implemented to control
      for age, education and occupation. A summary physical activity value unit for the
      24-hour period revealed a significantly greater mean value for white females
      (41.93 +/- 4.7) than for black females (40.01 +/- 3.9) suggesting white females
      were more physically active (p = .02) although this was not a function of
      biracial differences in play/recreation and exercise/sport type of activities.
      Although both black and white females were found to be sedentary (MET value < or
      = 2) over 90 percent of the time, black women are significantly more sedentary (p
      = .03). Biracial differences in discretionary non-exercise oriented activities
      may contribute to different rates of overweight observed between black and white
      women.

PMID- 8521148
TI  - The influence of change in marital status on weight change over one year.
AB  - Marital status is an influence on body weight. Changes in marital status and body
      weight were examined in the National Survey of Personal Health Practices and
      Consequences, a telephone survey of 2,436 adults interviewed twice approximately
      1 year apart. Two statistical methods for analyzing weight change were compared,
      and both produced similar results: regression analysis of weight change and
      regression analysis of weight at follow-up controlling for baseline weight. The
      findings revealed that women who entered marriage had greater weight change than
      women who remained married. Analysis of weight gain and weight loss separately
      showed that women who became married lost less weight than those who remained
      married. For men, there were no statistically significant relationships between
      marital change and weight change over a 1-year period. These findings support
      other literature showing that marital status plays a role in body weight changes.
      The results suggest gender differences may exist in the rate of body weight
      change after marriage, with more immediate changes in women than men.

PMID- 8521149
TI  - Comparison of obese NIDDM and nondiabetic women: short- and long-term weight
      loss.
AB  - Previous research suggests that overweight patients with diabetes lose less
      weight than nondiabetics. We compared the response of obese women with NIDDM to
      nondiabetic controls, matched for age and weight, to a behavior weight loss
      program. Forty-three overweight women (20 NIDDM, 23 nondiabetic) participated in
      the study. NIDDM and nondiabetic subjects were treated together and received the
      same 16-week behavioral weight loss program. Dependent measures included weight,
      3-day food records, physical activity, fasting plasma glucose, and questionnaires
      assessing eating behavior and depressive symptomatology. Weight loss of NIDDM and
      nondiabetic subjects at posttreatment was comparable (-7.4 +/- 5.3 kg vs. -6.4 +/
      3.8 kg, respectively). Changes in caloric intake, eating behavior, exercise and
      depressive symptomatology were also similar between the two groups. However,
      during the 1-year follow-up period, NIDDM subjects regained 5.4 +/- 6.1 kg
      compared to 1.0 +/- 6.7 kg for nondiabetics (p = .058). These data indicate that
      NIDDM subjects can lose as much weight as their nondiabetic peers during active
      treatment. Once treatment terminated, however, NIDDM subjects demonstrated poor
      weight loss maintenance. Thus the added motivation that comes from having
      diabetes and seeing improvements in glycemic control with weight loss were not
      sufficient to improve long term weight loss in diabetic subjects. A continuous
      care model of weight control may be particularly necessary for overweight
      patients with type II diabetes.

PMID- 8521150
TI  - Resistance to aging-associated obesity in capsaicin-desensitized rats one year
      after treatment.
AB  - Previous studies demonstrated reduced weight of abdominal white adipose tissue
      depots and of carcass fat in capsaicin-desensitized (Cap-Des) rats up to 8 months
      after treatment. The objective of the present study was to find out whether aging
      associated obesity and hyperplasia of retroperitoneal white adipose tissue was
      prevented in older (13.5 months old) Cap-Des rats, one year after treatment with
      Cap (done when they were 1.5 months old). The prevalence of obesity is known to
      increase in rats by this age. Abdominal white adipose tissue depots weighed less
      in old Cap-Des rats, both epididymal (9% less) and retroperitoneal (30% less).
      The number of mature white adipocytes was 28% less in the retroperitoneal depot
      but was not significantly different in the epididymal depot. Adipocyte size was
      not different. Carcass fat was less, both total and as percent of body weight.
      Food intake was normal for their reduced body size. The exponential increase in
      retroperitoneal white adipose tissue weight characteristic of aging rats that are
      becoming obese was virtually absent in Cap-Des rats. We conclude that lack of
      function of capsaicin-sensitive afferent autonomic nerves, known to be destroyed
      in Cap-Des rats, results in an alteration in energy balance conducive to
      leanness. We suggest that the attenuated age-associated increase in circulating
      CGRP (derived mainly from capsaicin-sensitive nerves) in the Cap-Des rat results
      in a lower degree of aging-associated insulin-resistance, hence in a lesser
      degree of obesity.

PMID- 8521151
TI  - Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of
      fluoxetine in obese female subjects.
AB  - Twelve nondepressed healthy female obese subjects (BMI > 30 kg/m2) took part in a
      study which conformed to a double-blind randomized crossover design. Each subject
      acted as her own control across 2 weeks of treatment with either 60 mg of the 5
      HT reuptake inhibitor fluoxetine or matching placebo. On days 7 and 14 of both
      treatment phases subjects were provided with fixed energy lunch meals high in
      either CHO or fat. The effect of these meals on satiety during the fluoxetine and
      placebo phases was assessed by a battery of procedures. Subjects felt less hungry
      after consuming the high CHO meal than after consuming the high-fat meal. They
      also felt less hungry when taking fluoxetine than when taking the placebo.
      Analysis of energy intake from the test meal revealed a main effect of prior
      lunch meal type (high CHO or high fat) and a main effect of drug treatment.
      Subjects consumed an average of 574 kcal following the high CHO meal compared to
      689 kcal following the high-fat meal. Subjects also consumed an average of 532
      kcal when taking fluoxetine compared to 730 kcal when taking the placebo.
      Fluoxetine did not exert any significant effects on macronutrient selection. Mean
      daily energy intake, calculated from food diary records, was 1881 kcal when
      subjects were taking the placebo compared to 1460 kcal when taking fluoxetine (a
      reduction of 22.4%). Fluoxetine treatment produced a significant weight loss of
      1.97 kg over the two weeks of treatment compared to a weight loss of only 0.04 kg
      on placebo.

PMID- 8521152
TI  - The indexing waltz.

PMID- 8521153
TI  - Does thermoregulatory feeding occur in newborn infants? A novel view of the role
      of brown adipose tissue thermogenesis in control of food intake.
AB  - The physiological significance of the extensive deposits of brown adipose tissue
      (BAT) in newborn human infants has been the subject of much experimentation and
      discussion. Because of its large thermogenic capacity, its function has usually
      been viewed as preparing the infant for producing heat in response to cold
      exposure at birth. Newborn infants are indeed capable of precise thermoregulation
      for a limited time over a rather limited range of ambient temperatures, from
      thermoneutrality (32-34 degrees C) down to common "room" temperatures (24-28
      degrees C). During such mild "cold-exposure", in response to a decrease in their
      skin temperature, their sympathetic nervous system activity increases, and they
      can more than double their resting metabolic rate, principally by thermogenesis
      in their BAT. This review puts forward an entirely new role for BAT thermogenesis
      in the cyclic feeding pattern of newborn infants during their first months of
      life. BAT thermogenesis is proposed to be an integral element in a physiological
      thermoregulatory feeding control mechanism in which extended periods of very
      gradual cooling are interspersed with episodes of increased sympathetic nervous
      system activity, increased heating via BAT thermogenesis, arousal, and feeding.
      The cry with which the baby attracts its mother's attention is an integral part
      of the mechanism, as is the nutritive suckling reflex and the behavior of the
      mother. Initiation of feeding is attributed to a transient dip in blood glucose
      concentration that is due to stimulation of glucose utilization in the BAT.
      Termination of feeding is attributed to the high temperature brought about by the
      stimulated BAT thermogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521154
TI  - The hypothalamic-pituitary-adrenal axis in obesity.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis normally maintains the
      concentration of cortisol within a narrow range with a diurnal variation
      characterized by higher cortisol concentrations in the morning and reduced levels
      in the evening. Excessive or deficient secretion of cortisol is associated with
      pathologic changes. Obesity has been linked with age, sex and racial alterations
      in the functioning of the HPA axis which are reviewed. The possible relationship
      of altered HPA axis activity with the long-term complications of obesity are
      considered.

PMID- 8521155
TI  - Laurence, Moon, Bardet, and Biedl: reflections on a syndrome.

PMID- 8521156
TI  - On congenital obesity syndrome with polydactyly and retinitis pigmentosa (a
      contribution to the study of clinical forms of hypophyseal obesity). 1920.

PMID- 8521157
TI  - Four cases of "retinitis pigmentosa" occurring in the same family, and
      accompanied by general imperfections of development. 1866.

PMID- 8521158
TI  - A pair of siblings with adiposo-genital dystrophy. 1922.

PMID- 8521159
TI  - Serum gamma-glutamyl transferase levels and coronary risk factors in middle-aged
      male and female nondrinkers.

PMID- 8521160
TI  - Do children lose and maintain weight easier than adults: a comparison of child
      and parent weight changes from six months to ten years.
AB  - Recent research has shown weight maintenance for obese preadolescent children
      over 60 and 120 month intervals, while studies on adults consistently show they
      fail to maintain weight loss. This paper is designed to examine differences in
      percent overweight changes at 6, 60 and 120 months in obese parents and children
      from 113 families who participated in randomized controlled outcome studies
      evaluating family-based behavioral treatment. Analyses showed children had
      significantly greater changes in percent overweight than their parents at each
      time point. Chi-Square and Logistic Regression analyses showed children were more
      likely than their parents at each time point to have percent overweight decreases
      greater than 20%, with over 20% of the children and less than 1% of the parents
      showing changes this large. The implications of these results for weight control
      are discussed. These results suggest there may be differences in the efficacy of
      treating obesity in children versus adults.

PMID- 8521161
TI  - Triglyceride uptake in muscles in rats.
AB  - Exogenous lipid is assimilated with different priorities in adipose tissue
      regions and varies in the fasting and fed conditions. The quantitative role of
      uptake of lipid in muscle has not been evaluated. In order to examine the uptake
      in other than adipose tissues, U14C-oleic acid in sesame oil was administered
      orally to conscious rats, and lipid label measured after different times in
      serum, heart, liver, mesenteric, retroperitoneal, inguinal and epididymal fat
      pads, as well as in red and white parts of gastrocnemius, extensor digitorum
      longus and soleus muscles. Lipid uptake in total adipose tissue was calculated
      from dissected adipose tissues plus lipids extracted from the eviscerated,
      skinned carcass. Lipid uptake in total muscle tissue was estimated from label in
      dissected muscles plus that in the carcass, assuming similar intracellular lipid
      contents and radioactivity as that averaged from dissected muscles. Lipid uptake
      in the liver was calculated from directly extracted lipid. Four hours after lipid
      administration to fed rats lipid radioactivity in heart and serum was minimal and
      had essentially disappeared at 8 hours. Liver label declined rapidly from peak
      values at or before 4 hours. Adipose tissue radioactivity increased gradually up
      to 16 hours and then decreased. Label in muscles was highest at 4 hours in the
      red gastrocnemius, and then decreased, while the other muscles showed a constant
      radioactivity over the observation period (24 hours). Radioactivity expressed per
      unit muscle mass seemed to be proportional to the oxidative capacity of
      muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521162
TI  - Body size preferences and desired weight of patients who have received obesity
      surgery and of comparison adults.
AB  - Patients who had received obesity surgery (n = 144) and comparison adults (n =
      72) selected the most attractive male and female size and the same-sex size they
      most wanted to look like from an array of 15 outline drawings. Subjects also
      reported their height, and current and desired weights (transformed into body
      mass index units [BMI]). There was a remarkable consensus on the sizes considered
      most attractive: Two male sizes were chosen by 78% of all subjects, and two
      female sizes by 83%. The hypothesis that adults who had obesity surgery would
      idealize thin sizes and, therefore, select thinner sizes and lower weights than
      comparison adults was not supported. Not only did patients and comparison adults
      select the same desired size, but women patients desired significantly larger
      BMIs than comparison women. There was a large range of desired BMIs associated
      with each desired size; the correlation between desired BMI and desired size was
      significant for women but not for men. It was speculated that subjects' desired
      size reflected cultural norms while subjects' desired BMI was a function of their
      current weight. Health professionals working in weight loss and/or physical
      fitness areas need to help clients understand weight-size relationships so that
      clients can have both realistic weight and realistic size goals.

PMID- 8521163
TI  - Body habitus changes among adult males from the normative aging study: relations
      to aging, smoking history and alcohol intake.
AB  - The Normative Aging Study (NAS) recruited 2280 Boston area healthy males aged 21
      to 80 in 1961 through 1970. Clinical exams have continued at 3- to 5-year
      intervals. Obesity was not an exclusion criterion. Stability in weight and body
      habitus among 867 adult participants in the NAS was evaluated at 5- and 15-year
      follow-ups. At study entry, age was linearly related to central adiposity
      [abdominal circumference (AC) and ratio of AC/Hip Breadth (HB)] throughout the
      entire age range (30 to 78 years) and linearly and quadratically related to
      weight (WT) and Body Mass Index (BMI) (kg/m2) with maximal values at age 50. Over
      15 years, changes in adiposity were strongly related to age; the greatest
      increases were among those initially 30 to 44 years of age with decrements in
      several adiposity measures (BMI, AC) only among the oldest subjects (60+ at
      entry); significant quadratic effects of age for BMI (p < .001), WT (p < .02) and
      AC (p < .01). There were major secular differences; men born later were heavier
      and fatter at the same ages as men born earlier. Men who gained (> 1 BMI) were
      younger while men who lost (> 1 BMI) had greater initial central adiposity than
      others. Smoking cessation was independently associated with increments in both
      central and peripheral adiposity. Moderate alcohol intake was associated with
      lower gains in AC/HB ratios at 15 years compared with little or high consumption.
      In general, aging was associated with trends towards central adiposity which
      tended to plateau or decrease at the oldest ages.

PMID- 8521164
TI  - Determination of beta 3-adrenoceptor mediated lipolysis in human fat cells.
AB  - The existence and relative importance of beta 3-adrenoceptors in man is still
      controversial. The aim of the present study was 1) to find further evidence for
      the existence of functional beta 3-adrenoceptors in human fat, and 2) to
      investigate factors that may influence this beta 3-adrenoceptor function. Fifty
      individuals were examined. Lipolysis mediated by the selective beta 3
      adrenoceptor agonist CGP 12177 in omental fat cells correlated with the response
      in subcutaneous fat cells. However, lipolysis was more pronounced in omental as
      compared to subcutaneous adipocytes, the intrinsic activity for CGP 12177 was 41%
      and 33%, respectively, while dobutamine, terbutaline and norepinephrine were full
      agonists. Both the lipolytic response and the sensitivity to CGP 12177 correlated
      with the effects of norepinephrine in the omental fat cells (r2 = 0.68 and 0.50,
      respectively, p = 0.0001). The beta 3-adrenoceptor mediated lipolytic response
      did also correlate with the responses induced by beta 1- and beta 2-agonists and
      by postreceptor acting agents. The antagonistic properties (pA2) of the beta
      adrenoceptor subtypes were also investigated. The pA2 for the selective beta 1-
      and beta 2-adrenoceptor antagonists versus CGP 12177-induced lipolysis were 2 to
      3 log units lower than those for the beta 1-antagonist versus dobutamine or for
      the beta 2-antagonist versus terbutaline. Furthermore, bupranolol had a
      significantly better antagonistic effect (pA2 7.17, p < 0.001) on the CGP 12177
      induced lipolysis than had the beta 1- and beta 2-adrenoceptor antagonists (pA2
      6.26 and 6.05, respectively). These data clearly support the existence of a third
      human beta-adrenoceptor. Several factors may contribute to the contradictory beta
      3-adrenoceptor results in man. The sensitivity of the different lipolytic systems
      vary considerably. Omental fat cells are preferable to subcutaneous cells for
      beta 3-adrenoceptor studies in man. The beta 3-responses are more attenuated in
      isolated fat cell preparations than in tissue fragments. Furthermore, as the beta
      3-adrenoceptor activity correlates to the norepinephrine activity, more
      pronounced effects will be expected in catecholamine sensitive subjects. At
      present, the number of tools available for beta 3-adrenoceptor studies are
      limited, and the receptor is hard to study, why it is essential to perform beta 3
      adrenoceptor studies under optimal conditions in order to obtain conclusive
      effects.

PMID- 8521165
TI  - Tissue oxidative capacity, fuel stores and skeletal muscle fatty acid composition
      in obesity-prone and obesity-resistant rats.
AB  - The purpose of the present study was to compare tissue oxidative capacity,
      skeletal muscle fatty acid composition, and tissue fuel stores in low-fat fed
      (LFD, 12% of energy from corn oil) male Wistar rats, and in high-fat fed (45% of
      energy from corn oil) obesity-prone (OP) and obesity-resistant (OR) male Wistar
      rats. Designation of OP and OR rats was based on body weight gain (upper tertile
      for OP; lower tertile for OR) after 5 weeks on the high-fat diet. Body weight
      gain over the 5-week dietary period was 91 +/- 9 g in LFD, 98 +/- 4 g in OR, and
      158 +/- 5 g in OP (p < 0.05 vs. LFD and OR). Energy intake over the 5-week
      dietary period was 3099 +/- 101 kcal in LFD, 3185 +/- 51 kcal in OR, and 3728 +/-
      45 kcal in OP (p < 0.05 vs. LFD and OR). Maximal citrate synthase activity
      (mumol.g-1.min-1) in the gastrocnemius muscle was not significantly different
      among groups: 12.1 +/- 2.4 in LFD, 11.4 +/- 1.9 in OR and 13.3 +/- 2.5 in OP
      rats. Similarly, citrate synthase activity in the heart, 59.3 +/- 7.2, and liver,
      6.6 +/- 0.4, was also not significantly different among groups. Fatty acid
      composition of the gastrocnemius muscle was not significantly different among
      groups. Fasting glycogen levels in the liver, gastrocnemius muscle, and heart
      were 6.4 +/- 3.7, 13.2 +/- 2.3 and 6.8 +/- 1.9 mumol/g in LFD, 21.2 +/- 5.1 (p <
      0.05 vs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521166
TI  - Effects of obesity and gender on insulin receptor expression in liver of SHHF/Mcc
      FAcp rats.
AB  - In SHHF/Mcc-FAcp rats (formerly SHR/Mcc-cp), obesity and male gender
      synergistically modulate hyperinsulinemia, insulin resistance and predisposition
      to diabetes. Our previous studies showed gender and obesity modulate hepatic cell
      surface insulin binding and insulin clearance additively. Hepatic insulin
      receptors (IR) bind insulin as a first step in insulin clearance through
      internalization and degradation. We hypothesize that the synergistic effects of
      obesity and gender on hepatic insulin binding and clearance result from
      interaction of these two factors on hepatic IR expression. To address IR
      expression in SHHF/Mcc-FAcp rats, we quantitated IR protein levels in detergent
      solubilized liver homogenates by Western blotting and IR mRNA levels by a
      solution hybridization/RNase protection assay. Obesity reduced total hepatic IR
      content in males and females, 50% and 68% respectively. Male gender reduced IR
      protein content 24% in lean, but had no effect on IR protein content in obese
      rats. Neither gender nor obesity affected hepatic IR mRNA content. Thus, obesity
      appears to affect hepatic IR protein content and cell surface binding through
      post-transcriptional mechanisms; similarly, male gender in lean rats reduces IR
      protein levels and cell surface binding through mechanisms not involving changes
      in mRNA levels. In obese rats, the synergistic effects of male gender appears to
      involve changes in IR trafficking and consequently cell surface insulin binding
      and processing.

PMID- 8521167
TI  - The NAASO position paper on approval and use of drugs to treat obesity.

PMID- 8521168
TI  - Guidelines for the approval and use of drugs to treat obesity. A position paper
      of The North American Association for the Study of Obesity.

PMID- 8521169
TI  - Self-esteem and obesity in children and adolescents: a literature review.
AB  - The relationship between self-esteem and obesity has not received a great deal of
      empirical evaluation using strong research methodologies. Thus, it is not clear
      whether self-esteem is consistently related to obesity, whether the relationship
      is global or specific to physical appearance, whether the relationship differs by
      demographic variables such as age, gender or race/ethnicity, or whether self
      esteem moderates weight changes during weight loss treatment programs. This
      review examines these questions using empirical evidence from 35 studies on the
      relationship between self-esteem and obesity in children and adolescents.
      Thirteen of 25 cross sectional studies clearly showed lower self-esteem in obese
      adolescents and children. Five of the six cross-sectional studies that included a
      measure of body esteem found lower body esteem in obese compared to normal weight
      children and adolescents. Results from two prospective studies examining initial
      self-esteem and later obesity were inconsistent. Results from six of eight
      treatment studies showed that weight loss treatment programs appear to improve
      self-esteem. However, it is unclear whether increases in self-esteem are related
      to enhanced weight loss. Many studies were methodologically weak primarily due to
      small and select samples and lack of appropriate comparison groups. Implications
      for prevention and treatment of childhood obesity are discussed.

PMID- 8521170
TI  - Luxuskonsumption--myth or reality?

PMID- 8521171
TI  - Experimental contributions to the science of human daily nutritional needs with
      particular regard to the necessary amount of protein (author's experiments).
      1902.

PMID- 8521172
TI  - A study of weight regulation in the adult human body during over-nutrition. 1922.

PMID- 8521173
TI  - The doubtful nature of "luxuskonsumption". 1931.

PMID- 8521174
TI  - Food reactions in pollen and latex allergic patients.

PMID- 8521175
TI  - Nasal polyps--a model of chronic respiratory mucosal inflammation.

PMID- 8521177
TI  - Genetic abnormalities of the human beta 2 adrenergic receptor.

PMID- 8521176
TI  - Good allergy practice--standards of care for providers and purchasers of allergy
      services within the National Health Service. Royal College of Physicians and
      Royal College of Pathologists.
AB  - Allergic diseases affect at least 15% of the population and are the cause of much
      ill-health. 'Clinical immunology and allergy', the term used by the Department of
      Health in England and Wales for this area of specialization, is recognized as a
      separate specialty of medicine under the National Health Service. Many organ
      based hospital consultants (e.g. chest physicians) have allergy as a special
      interest or subspecialty. Allergists deal largely with 'itch, sneeze, cough and
      wheeze' and so are experts in: summer hay fever (seasonal, allergic,
      conjunctivorhinitis); perennial rhinitis (symptoms of a 'permanent cold');
      allergic asthma (including occupational asthma); allergy to stinging insects
      (especially wasps and bees); allergy to drugs; allergy-related skin disorders,
      i.e. urticaria, angioedema, atopic eczema and contact dermatitis; food allergy
      and food intolerance; anaphylaxis (acute generalized allergic reaction);
      evaluating the role of allergy in non-specific/polysymptomatic illness. Children
      with allergic disease should be under the overall care of a paediatrician since
      the progression of allergies in children differs from that in adults. Good
      allergy practice involves teamwork by doctors, nurses and dietitians. The
      investigation of allergy patients includes skin tests and challenge procedures
      (e.g. food allergy tests) as well as various specialized laboratory
      investigations. Good clinical practice by providers and the effective use of
      allergy services by purchasers should improve prognosis and cut costs of
      treatment in allergic disease.

PMID- 8521178
TI  - Allergenic relationship between taxonomically diverse pollens.
AB  - BACKGROUND: Skin tests and tests for IgE antibodies show that subjects are
      usually sensitive to a number of different pollens, frequently from taxonomically
      diverse species which are assumed to be allergenically non-crossreactive. This
      suggests that the presence of IgE antibody-reactivity to an individual pollen may
      not necessarily have resulted from contact with that pollen or even with a
      taxonomically closely related species. OBJECTIVE: Since this has important
      consequences for allergen avoidance and desensitization of patients, we attempted
      to define allergenic relationships between diverse pollen species. METHODS: Sera
      from subjects were examined in direct IgE antibody binding experiments and by
      quantitative inhibition, protein blotting and adsorption and elution studies.
      RESULTS: Sera from subjects diagnosed as allergic to white cypress pine, Italian
      cypress, ryegrass or birch pollen were shown to have IgE antibodies that reacted
      with pollens from these four species and from cocksfoot, couch grass, lamb's
      quarter, wall pellitory, olive, plantain and ragweed. These reactions were
      confirmed in protein blotting and adsorption and elution studies where numerous
      IgE-binding bands were detected in all 11 different pollen extracts with sera
      from each of the different allergic categories. Further evidence of allergenic
      (i.e. IgE-binding crossreactivity between the different pollens was provided by
      inhibition studies in which clear-cut inhibitions of IgE binding to the different
      pollen allergen discs were obtained with comparable amounts of the different
      pollen extracts. CONCLUSION: We conclude that the presence of pollen reactive IgE
      antibodies may not necessarily be a true reflection of sensitizing pollen
      species.

PMID- 8521179
TI  - Cytokine gene expression and release from epithelial cells. A comparison study
      between healthy nasal mucosa and nasal polyps.
AB  - BACKGROUND: Epithelial cells release cytokines and they probably contribute to
      chronic inflammation detected in bronchial asthma, rhinitis and nasal polyposis.
      OBJECTIVES: To investigate the effect of cultures on cytokine gene expression to
      compare epithelial cell cytokine release by both healthy nasal nucosa (HNM) and
      nasal polyps (NP), and the modulation by dexamethasone and to investigate which
      cytokines may promote eosinophil survival. METHODS: Epithelials cells were
      cultured to confluence, human epithelial cell conditioned media generated with or
      without dexamethasone, and supernatants measured by ELISA. Cytokine gene
      expression was investigated by reverse transcription-polymerase chain reaction
      (RT-PCR). RESULTS: Fresh epithelial cells only expressed mRNA for intesleukin-8
      (IL-8) and granulocyte macrophage-colony stimulating factor (GM-CSF) while
      cultured cells expressed mRNA for IL-1 beta, IL-6, IL-8, tumour necrosis factor
      alpha (TNF alpha) and GM-CSF. Epithelial cells from NP significantly (P < 0.05)
      released more IL-8 (25431 +/- 3163 pg/mL), and GM-CSF (1229 +/- 391 pg/mL) than
      those from HNM (18604 +/- 1723 pg/mL for IL-8; and 611 +/- 98 pg/mL for GM-CSF).
      Dexamethasone 10 microM inhibited the release of all cytokines, this effect being
      similar (40-50%) in both HNM and NP, except for IL-6 which was higher in HNM.
      Eosinophil survival induced by epithelial cell secretions from both HNM and NP
      was strongly blocked by GM-CSF antibody while it was partially blocked by
      antibodies to TNF alpha and IL-8. CONCLUSIONS: These findings suggest that
      although epithelial cell culture procedures may upregulate cytokine gene
      expression, nasal polyps may represent a more active inflammatory tissue by
      releasing more cytokines than healthy nasal mucosa this release being inhibited
      by steroids; and that, in addition to GM-CSF, other cytokines such as TNF alpha
      and IL-8, may also be involved in the promotion of eosinophil survival.

PMID- 8521180
TI  - Cyclic nucleotide phosphodiesterases from purified human CD4+ and CD8+ T
      lymphocytes.
AB  - BACKGROUND: CD4+ and CD8+ T-lymphocytes are suggested to differentially affect
      airway inflammation in asthma. Agents which increase intracellular cAMP levels,
      such as PDE inhibitors, have been shown to diminish lymphocyte growth and
      differentiation, and to affect cytokine expression. Differences in the PDE
      isoenzyme profile between CD4+ and CD8+ cells might form a basis to
      differentially modify their functions by PDE inhibitors. OBJECTIVE: The study
      investigates and compares the PDE isoenzyme activity profiles of human peripheral
      blood CD4+ and CD8+ T-lymphocytes. METHODS: CD4+ and CD8+ T-lymphocytes were
      purified (> 98%) from peripheral blood mononuclear cells by negative selection.
      PDE isoenzyme activity profiles were investigated using PDE isoenzyme selective
      inhibitors and activators. RESULTS: In CD4+ and CD8+ T-lymphocyte homogenates,
      PDE IV and PDE III activities were the predominant PDE isoenzyme activities at
      0.5 microM cyclic nucleotide substrate concentrations. PDE IV was localized in
      the soluble fraction whereas PDE III was membrane bound. Low PDE I, II and V
      activities were detected. About 20% of total cAMP hydrolysing capacity at 0.5
      microM cAMP was insensitive to PDE isoenzyme selective inhibitors and activators
      and therefore could not be assigned to PDE I-IV. The PDE isoenzyme pattern was
      not different between CD4+ and CD8+ T-lymphocytes. Moreover, representative
      inhibitors of PDE III and IV activity inhibited cAMP hydrolysis in soluble
      fractions of both T-lymphocyte subsets with similar potency. Enzyme kinetic
      analysis similarly did not reveal differences between CD4+ and CD8+ T
      lymphocytes. CONCLUSION: Normal CD4+ and CD8+ T-lymphocytes are likely to be
      equally sensitive targets for the effects of PDE inhibitors.

PMID- 8521181
TI  - Cyclic nucleotide phosphodiesterase isoenzyme activities in human alveolar
      macrophages.
AB  - BACKGROUND: Alveolar macrophages and their precursors, the monocytes are involved
      in airway inflammation in asthma. An increase in intracellular cAMP by PDE
      inhibitors is known to suppress macrophage and monocyte functions. A comparison
      of the PDE-isoenzyme profiles of human alveolar macrophages from normal and
      atopic donors and of human peripheral blood monocytes might form a basis to
      differentially affect functions of these cells by PDE inhibitors. OBJECTIVE: The
      study compares the PDE isoenzyme activity profiles of human alveolar macrophages
      from normal and atopic asthmatic donors and human peripheral blood monocytes. In
      addition, the effect of in vitro maturation of monocytes on their PDE isoenzyme
      profile is studied. METHODS: Macrophages were purified (95-97%) by adherence to
      plastic, and blood monocytes were purified (88%) by counter-current elutriation.
      PDE isoenzyme activity profiles were investigated using isoenzyme selective
      inhibitors and activators. RESULTS: In macrophages substantial PDE I activity,
      which was significantly higher than PDE III-V activity was detected and PDE II
      was absent. PDE III was membrane-bound whereas PDE I, IV and V were soluble. No
      difference was found between alveolar macrophages of normal donors and atopic
      asthmatics. Monocytes exclusively contained PDE IV but their in vitro maturation
      led to a PDE isoenzyme profile similar to that of alveolar macrophages.
      CONCLUSION: These results indicate that human monocytes and alveolar macrophages
      are distinct targets for the effects of selective PDE inhibitors while alveolar
      macrophages from normal and atopic individuals appear to be equally sensitive.

PMID- 8521182
TI  - Inhalant allergen-specific T-cell reactivity is detectable in close to 100% of
      atopic and normal individuals: covert responses are unmasked by serum-free
      medium.
AB  - BACKGROUND: It is widely held that in vitro T cell responses to allergens are
      more prominent in atopic than in normal individuals, though this conclusion is
      based upon culture techniques which fail to detect proliferative responses in a
      significant minority of atopics and many normals. OBJECTIVES: Study allergen
      specific proliferative responses of T cells cultured in serum-free medium (SFM).
      Examine associations between atopic status, age and T cell reactivity. METHODS:
      Initially, peripheral blood mononuclear cells were stimulated with allergens or
      antigens in SFM, and compared with cells cultured in RPMI + 10% fetal calf serum
      or human AB serum. Subsequently, T cell reactivity was studied in 34 adults (20
      49 years), 27 children (2-13 years), and 19 infants (< or = 10 weeks) using SFM
      alone. RESULTS: Compared with serum-supplemented medium, SFM enhanced net T cell
      proliferation, both in bulk culture and when cloning at limiting dilution. In
      many subjects, SFM unmasked T cell reactivity to allergens which was not
      otherwise evident, and lowered the threshold allergen levels required for in
      vitro T cell triggering. For most allergens, T cell proliferative responses did
      not differ between adults who had specific IgE, and those who did not. The most
      vigorous responses observed were to ubiquitous inhalant allergens, which
      stimulated T cells from close to 100% of adults and children, and over 60% of
      infants. In contrast, responses to the 'vaccine' antigen tetanus toxoid were
      completely absent in the latter age group, but present in the majority of adults
      and children. CONCLUSIONS: These findings suggest that the extent of active T
      cell recognition of environmental allergens has been hitherto underestimated, and
      further that these responses may frequently be initiated in very early life.
      Additionally, these findings reinforce the notion that qualitative (as opposed to
      quantitative) variations in specific T cell reactivity ultimately determine
      allergen responder phenotype.

PMID- 8521183
TI  - Factors related to the development of sensitization to green coffee and castor
      bean allergens among coffee workers.
AB  - BACKGROUND: Occupational allergic respiratory symptoms in coffee workers have
      been frequently reported, but the ultimate cause of sensitization is still
      debated, castor bean being considered besides green coffee beans. Atopy and
      cigarette smoking have been suggested as promoting factors of sensitization for
      several occupational allergens. OBJECTIVE: This study was carried out to assess
      the prevalence of allergic respiratory symptoms and of sensitization to both
      green coffee beans and castor bean in the whole workforce of a coffee
      manufacturing plant. Furthermore we wanted to ascertain both the presence of
      castor bean antigens in the settled dust of the green coffee beans warehouse and
      the possible crossreactivity between the two beans. Meanwhile, the effect of
      smoking and atopy was considered. METHOD: Two-hundred and eleven workers were
      examined. A questionnaire on oculorhinitis and asthma was administered and skin
      prick tests for green coffee beans, castor bean and 15 common inhalant allergens
      were carried out. Isoelectric focusing, isoelectric focusing immunoblot and
      radioallergosorbent assay (RAST) inhibition were performed on samples of settled
      environmental dust from the green coffee area, as well as on castor bean and
      green coffee beans. RESULTS: Ten per cent of the workers complained of
      oculorhinitis alone and 16% of asthma (nearly always associated with
      oculorhinitis). The overall prevalence of skin-sensitization was: 15% for green
      coffee beans, 22% for castor bean, 22% for common allergens. Evidence of
      sensitization to occupational allergens was more common in smokers, with a more
      than twofold increase in relative risk. The strong association between skin
      positivity to common and occupational allergens suggests that atopy acts as an
      enhancing host factor towards occupational sensitization. The analysis of the
      dust confirmed the presence of castor bean antigens. CONCLUSION: Our findings
      indicate that castor bean is the major cause of occupational sensitization among
      coffee workers, whereas smoking and atopy act as enhancing factors.

PMID- 8521184
TI  - Evaluation by SDS-PAGE and immunoblotting of residual antigenicity in hydrolysed
      protein formulas.
AB  - BACKGROUND: Extensively hydrolysed protein formulas are widely used as an
      alternative diet for children with cow's milk allergy. Partially hydrolysed
      protein formulas have been noted in some studies as useful in the prevention of
      allergy in infants at high risk of atopy. Although normally well tolerated, these
      'hypoallergenic' products have been reported to cause serious immunological
      reactions in very sensitive subjects. OBJECTIVE: Starting from these
      considerations, we studied some commercial hydrolysed formulas in search of
      biological data supporting the observed clinical reactions. METHODS: We set up an
      electrophoretic method sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) which allowed us to study the molecular weight of peptides contained
      in hydrolysed products. Then, using the immunoblotting technique we evaluated the
      reactivity of circulating IgE (from serum of children allergic to cow's milk
      proteins) with the residual intact proteins and with the peptides present in
      these formulas. RESULTS: Both group of milk proteins (caseins and whey proteins)
      were important allergens for children included in this study. The presence of
      high-molecular polypeptides was shown in partial hydrolysed formulas as such and
      in extensive hydrolysed products after protein enrichment by trichloroacetic acid
      (TCA) precipitation. Intact residual proteins were mainly responsible for the
      formation of IgE-antigen complexes observed in immunoblotting. More rarely,
      polypeptides of partial hydrolysed formulas were involved in immunological
      responses. CONCLUSIONS: Both partial and extensive hydrolysed formulas could
      induce clinical reactions in very sensitive subjects. These responses are mainly
      associated with allergy to the small amounts of residual intact proteins.

PMID- 8521185
TI  - Prohevein from the rubber tree (Hevea brasiliensis) is a major latex allergen.
AB  - BACKGROUND: There is general agreement that proteins eluting from different
      natural rubber latex products can cause immediate type hypersensitivity reactions
      in latex-allergic patients. However, there is as yet no consensus as to what are
      the most important allergens in natural rubber latex. OBJECTIVE: We wanted to
      purify and characterize at the primary structure level three natural latex
      proteins, suggested to represent significant allergens. METHODS: Proteins were
      purified from ultracentrifuged bottom fraction of natural rubber latex using high
      performance liquid chromatography gel filtration and reversed phase
      chromatography. Purified proteins were subjected to tryptic cleavage, peptide
      separation and amino acid sequencing. Immunoblotting was used to demonstrate IgE
      antibodies to the purified proteins in sera from latex-allergic patients.
      RESULTS: A 20 kDa protein was identified by amino acid sequencing as prohevein, a
      major protein in the rubber tree Hevea brasiliensis, and a 30 kDa natural rubber
      latex protein as hevamine, another essential rubber tree protein. A third,
      previously undescribed natural rubber latex protein, showed high homology to
      several plant endo-1,3-beta-glucosidases. In immunoblotting, the purified
      prohevein bound IgE antibodies from 24/29 (83%) sera of latex-allergic patients
      including positive results in 4/6 latex-allergic children with spina bifida or
      other congenital anomalies. The purified prohevein elicited positive skin-prick
      test reactions in all six latex-allergic patients showing IgE to prohevein. The
      purified 36 kDa protein bound IgE from 6/29 (21%) latex-allergic sera, and the
      purified hevamine from only 1/29 patient sera. CONCLUSION: The observed high
      frequency of IgE antibodies to prohevein suggests that this protein is a major
      natural rubber latex allergen.

PMID- 8521186
TI  - Speleotherapy in asthma and allergic diseases.

PMID- 8521187
TI  - The major mite allergen Der p 2--a secretion of the male mite reproductive tract?

PMID- 8521188
TI  - Three year IGF-I treatment of children with Laron syndrome.
AB  - Nine prepubertal children with Laron syndrome (6 males, 3 females) aged 0.5 to
      14.6 years were treated by daily subcutaneous injections of IGF-I in doses of 150
      200 micrograms/kg. All patients completed at least one year of treatment; six
      completed two years and five three years. During the first year, a significant
      increase in linear growth velocity, from a mean +/- SD of 4.7 +/- 1.3 to 8.2 +/-
      0.8 cm/yr (p < 0.0001), was registered. In the second year the growth velocity
      was lower, but still significantly higher than before treatment. Bone maturation
      advanced proportionally with chronological age. A reduction in subcutaneous fat
      tissue was observed despite the body weight increase. There was no aggravation of
      the characteristic hypoglycemic episodes; on the contrary, there was a better
      tolerance to fasting. Significant increases in serum alkaline phosphatase,
      phosphorus and procollagens were registered throughout the study. In conclusion,
      IGF-I provides an effective replacement treatment for IGF-I-deficient children,
      mimicking most effects ascribed to growth hormone.

PMID- 8521189
TI  - Severe growth hormone insensitivity (Laron syndrome) due to nonsense mutation of
      the GH receptor in brothers from Russia.
AB  - Primary GH insensitivity (Laron syndrome) due to GH receptor deficiency (GHRD) is
      an autosomal recessive condition characterized by severe growth failure. Diverse
      alterations in the GHR gene have been reported in affected individuals. We report
      here the first family with GHRD from Russia, with two affected siblings and
      consanguineous parents. Analysis of blood spot DNA by polymerase chain reaction
      (PCR), denaturing gradiant gel electrophoresis, and nucleotide sequencing
      indicated that these siblings are homozygous for a nonsense mutation, R43X, in
      the GHR gene. The R43X mutation, which changes an arginine codon to a
      translational stop codon, occurs at a CpG dinucleotide mutational hotspot and has
      previously been identified in affected individuals of Mediterranean and
      Ecuadorian origin.

PMID- 8521190
TI  - Effects of two years of growth hormone treatment in short, slowly growing non
      growth hormone deficient children.
AB  - Thirty-two short, slowly growing prepubertal children with normal GH levels
      (after clonidine stimulation and overnight sampling) were treated with GH hormone
      for 2 consecutive years at a dose of 0.1 IU/kg/day s.c. Fifteen similar children
      were followed for 2 years without therapy (controls). Height velocity increased
      in our treated group from 3.8 +/- 0.9 cm/yr to 7.3 +/- 1.3 cm/yr and 7.1 +/- 0.9
      cm/yr in the first and second years of therapy, with 85.7% and 87.5% of our
      patients growing > 2 cm/yr above baseline. Height SDS changed from -2.4 +/- 0.4
      to -2.0 +/- 0.7 in the first year and to -1.8 +/- 0.5 during the second year of
      treatment, while bone ages increased at a slightly higher rate than chronological
      ages. An increase in the final height predictions of our patients during therapy
      was noted. Height velocity increment in the control group was not significant and
      height SDS of this group did not change. GH therapy in short, slowly growing non
      GH deficient children seems to be effective and safe in the short term; however,
      its efficacy in increasing the final height of this group of patients is still
      undetermined.

PMID- 8521191
TI  - A partial transient effect of short-term growth hormone (GH) treatment in short
      non-GH deficient prepubertal children.
AB  - This study reports the growth of 11 short non-GH deficient children before,
      during short-term GH therapy for 1 year and for 2 years after the cessation of
      treatment. The mean growth velocity increased significantly (p < 0.0001) from the
      pretreatment mean of 4.6 (SD = 0.95) cm/year to 8.4 (SD = 1.1) cm/year after 1
      year of GH treatment without accelerated advancement of skeletal maturation. The
      serum IGF-1 levels also increased significantly with treatment. In nine children
      who remained prepubertal followed for one year after GH treatment, the mean
      growth velocity increased from 4.5 (SD = 0.69) cm/year before treatment to 8.7
      (SD = 1.28) cm/year after 1 year of GH treatment (p < 0.0001). After stopping GH
      treatment, the growth velocity decreased significantly (p < 0.001) to 2.4 (SD =
      0.68) cm/year during the first year of follow-up. In the six prepubertal children
      followed up for 2 years after treatment, the mean growth velocity was 4.1 (SD =
      1.04) cm/year which was not significantly different from the pretreatment growth
      velocity. The significant decrease in growth velocity during the first post
      treatment year could not be explained by the usual fall of growth velocity with
      increasing age in prepubertal children. Our results indicate that the effect of
      one year of GH treatment on height gain is partly transient and cast doubt on the
      efficacy of short-term GH therapy in short non-GH deficient patients.

PMID- 8521192
TI  - Growth and puberty in thalassemia major.
AB  - Growth and sexual development were evaluated in 54 (29 female, 25 male) patients
      with beta-thalassemia major aged 2.7-21.3 years (mean 10.4 yr). Mean
      pretransfusion hemoglobin concentration was 7.8 +/- 0.7 mg/dl. All patients
      except 6 were on desferrioxamine. Age of starting of therapy was 6.8 +/- 3.9
      years. Mean SDS values for height, weight and sitting height were significantly
      lower (p < 0.001) than control cases of similar age. Height deficiency exceeded 
      2 SD in 18 patients and a delay in bone age (> 2 SD below the mean) was observed
      in 36 out of 54 patients. Among 11 patients over 14 years, 9 showed delay in
      onset or progression of puberty and 10 had growth retardation. Height SDS were
      negatively correlated with chronological age, age of onset of desferrioxamine and
      present serum ferritin levels (p < 0.001). These findings indicate that abnormal
      growth and delayed puberty are frequent in transfusion dependent thalassemics.
      These can be partly overcome by early onset of chelating therapy.

PMID- 8521193
TI  - Surgical stress and neuroendocrine responses in infants and children.
AB  - We studied the stress hormone response to surgery in 42 infants and children.
      Plasma levels of the stress hormones ACTH, cortisol, beta-endorphin and arginine
      vasopressin (AVP) were determined on three occasions, i.e., one day before
      surgery, 60 to 90 minutes after skin closure and on the day after surgery
      (anesthesia by halothane and nitrous oxide). We observed an increase in the
      levels of both ACTH and cortisol in most patients after surgery, although there
      was no correlation between them. Beta-endorphin levels, on the other hand, rose
      after surgery and correlated significantly with ACTH in 30 patients. A steep rise
      in AVP levels was found in 84% of the subjects, a phenomenon that could not have
      been due only to osmotic or cardiovascular stimuli. The values of all the stress
      hormones declined and normalized on the day after surgery. We conclude that
      routine surgery in infancy or childhood induces a dramatic, albeit transient,
      stimulation of neuroendocrine stress hormones.

PMID- 8521194
TI  - Transient autonomic neuropathy in an adolescent with insulin dependent diabetes
      mellitus.
AB  - A 15 year-old girl with insulin dependent diabetes mellitus of 11 years duration
      developed severe neuropathy involving the bladder and stomach. The bladder
      recovered after 2 months of intermittent catheterization. Metoclopramide relieved
      the gastric symptoms. Gastric emptying was normal after 2 further months of
      treatment. The neuropathy developed in spite of a mean HbA1c of 7.4% suggesting
      that factors in addition to glycemic control play a role in the development of
      the complications of insulin dependent diabetes mellitus.

PMID- 8521195
TI  - Testosterone induced priapism in two adolescents with sickle cell disease.
AB  - Priapism is common in pubertal males with sickle cell disease, but the
      association between low-dose exogenous testosterone administration and priapism
      in such patients has not been well documented. Two adolescents with homozygous
      sickle cell disease (SCD) and delayed maturation with behavioral problems
      developed priapism about one week after receiving an intramuscular injection of
      testosterone enanthate. Neither had a previous history of priapism. We conclude
      that testosterone should not be administered to male patients with SCD because of
      the risk of inducing priapism and possible impotence.

PMID- 8521196
TI  - Pseudohypoparathyroidism type Ia and growth hormone deficiency in two siblings.
AB  - Pseudohypoparathyroidism type Ia (PHP type Ia) is associated with several
      endocrinopathies. We describe two siblings with PHP type Ia, hypothyroidism and
      growth hormone deficiency (GHD). To our knowledge, these patients are the first
      to have PHP type Ia and GHD. The defect which is most likely responsible for the
      three endocrinopathies is a deficiency of the stimulatory guanine nucleotide
      binding regulatory protein, Gs.

PMID- 8521197
TI  - Therapy-resistant seizures in pseudohypoparathyroidism. A case report.
AB  - A 30 year-old, mentally retarded female presented with uncontrolled seizures. The
      diagnosis of pseudohypoparathyroidism was established on grounds of clinical,
      laboratory and radiological evaluation. Despite normalization of serum calcium
      levels with vitamin D treatment, the patient continued to suffer from frequent
      convulsions. The possible pathogenesis of the therapy-resistant seizures and the
      therapeutic approach are discussed.

PMID- 8521198
TI  - Bedside ultrasonographic evaluation of hemoperitoneum: the time has come.

PMID- 8521199
TI  - Clinical diagnosis in emergency medicine: lost art, or lost cause?

PMID- 8521200
TI  - Recapturing expertise in the physical examination: is it too late?

PMID- 8521201
TI  - Reducing the door-to-drug interval for thrombolytic therapy.

PMID- 8521202
TI  - Evaluation of hemoperitoneum using a single- vs multiple-view ultrasonographic
      examination.
AB  - OBJECTIVE: To compare the sensitivities, specificities, and accuracies between a
      single-view ultrasonography (US) technique and a multiple-view technique for
      identifying hemoperitoneum in multiple-trauma patients. METHODS: Data from a
      prior prospective study of US for trauma diagnosis at a level I trauma center
      were retrospectively analyzed. A convenience sample of adult patients (> or = 18
      years of age) who had presented with major blunt or penetrating torso trauma and
      had undergone rapid trauma US examinations to detect hemoperitoneum were
      reviewed. The US interpretations by emergency physicians had been recorded prior
      to obtaining other diagnostic tests. Five views were evaluated, including the
      right intercostal oblique view examining Morison's pouch. Evidence of free
      intraperitoneal fluid by exploratory laparotomy, CT, or diagnostic peritoneal
      lavage (DPL) was used as the criterion standard. RESULTS: Of the 245 patients
      entered into the study, 37 had free intraperitoneal fluid, confirmed by CT, DPL,
      or exploratory laparotomy. With the multiple-view technique, US was 87% (95% CI =
      71%, 96%) sensitive, 100% (95% CI = 97%, 100%) specific, and 98% (95% CI = 95%,
      100%) accurate. The single-view technique, evaluating only Morison's pouch, was
      51% (95% CI = 34%, 68%) sensitive, 100% (95% CI = 98%, 100%) specific, and 93%
      (95% CI = 89%, 96%) accurate. CONCLUSIONS: An initial trauma US examination using
      a multiple-view technique is more sensitive than that using a single-view
      technique for detecting hemoperitoneum in trauma patients.

PMID- 8521203
TI  - Histopathologic evaluation of the therapeutic efficacy of water and milk dilution
      for esophageal acid injury.
AB  - OBJECTIVE: To determine whether acid-induced injury to the esophagus is decreased
      by early dilutional therapy with water or milk. METHODS: A controlled in-vitro
      animal model for acid injury to the esophagus was carried out using esophagi
      harvested from 70 Sprague-Dawley rats of both sexes and weighing 250-350 g. One
      control and six experimental groups each containing ten esophagi were instilled
      with 1 mL of 0.5 normal solution of hydrogen chloride (N HCl). Dilution with
      water or milk was performed at 0, 5, or 30 minutes postinjury in the experimental
      groups. No dilution was performed with the control group. Specimens were
      maintained in an oxygenated saline bath for a 60-minute experimental period and
      then fixed in 10% formalin for histologic evaluation. Injury severity was rated
      by blinded histopathologic examination using scores of 0 (no injury), 1 (minor),
      2 (moderate), and 3 (severe) for the histopathologic categories: cornified
      epithelial cells (CEs), granular cells (GCs), granular cell nuclei (GNs), and
      basal cells (BCs). Red blood cells were scored as positive or negative for lysis.
      RESULTS: The controls showed the most severe outcomes. Significant differences in
      injury occurred for all time periods and histopathologic categories, except for
      the GN/water and BC/milk histopathologic category/treatment groups. However, a
      linear trend analysis was significant for all histopathologic categories except
      BC. These analyses support decreased injury in the earlier treated groups. Injury
      severity was highest in the most superficial cell layer (CE). CONCLUSIONS:
      Emergency therapy with water or milk reduces acute acid injury to the esophagus.
      Earlier treatment is associated with decreased injury severity. This research
      supports the use of dilutional therapy with water or milk for acute acid injury
      to the esophagus.

PMID- 8521204
TI  - Out-of-hospital provider use of epinephrine for allergic reactions: pilot
      program.
AB  - OBJECTIVE: To describe experience with an out-of-hospital provider program for
      the recognition and field management of allergic reactions by advanced life
      support (ALS) and basic life support (BLS) providers. METHODS: Data sheets
      completed between June 1, 1988, and August 31, 1993, and records from receiving
      sites (physicians' offices or EDs) were reviewed for information regarding the
      presentation of the allergic reaction, the time course and treatment provided out
      of hospital, and the clinical outcome at the receiving health care facility.
      RESULTS: Thirty-seven data sheets were completed during the study period.
      Fourteen (38%) of the providers were BLS providers. The epinephrine was supplied
      from the emergency medical services (EMS) provider's personal kit in 35% of the
      cases, from an EMS vehicle in 57% of the cases, and by the patient in 8% of the
      cases. Availability of the kits allowed administration of epinephrine prior to
      the arrival of the first EMS vehicle in 41% of the instances and prior to
      physician on-line medical command in 65% of all the instances (predominantly by
      BLS providers). Overall, 77% of the patients experienced alleviation of their
      symptoms of respiratory difficulty, swelling, or rash after epinephrine
      administration, while 20% were unchanged and 3% worsened. All patients receiving
      epinephrine had an ED diagnosis of allergic reaction, and no adverse event was
      encountered on follow-up of the patients treated. CONCLUSIONS: Severe allergic
      reactions can be reliably identified and safely managed by out-of-hospital
      providers, including BLS providers. Providing personal anaphylactic treatment
      kits and increasing the pool of providers trained to manage allergic reactions
      (including BLS providers) can often decrease the time to treatment.

PMID- 8521205
TI  - Intravenous chlorpromazine vs intravenous metoclopramide in acute migraine
      headache.
AB  - OBJECTIVE: To compare the efficacy of IV chlorpromazine with that of IV
      metoclopramide in the treatment for acute migraine headache in the ED. METHODS: A
      prospective randomized double-blind trial was undertaken at two university
      affiliated urban EDs with a combined annual census of more than 85,000 patients.
      Included in the study were patients presenting to the ED with a diagnosis of
      migraine headache. The subjects were randomized to receive 0.1 mg/kg/dose IV of
      either chlorpromazine (CPZ) or metoclopramide (MC), up to a total of three doses.
      RESULTS: Ninety-one patients completed the protocol; 44 received MC and 47
      received CPZ. The demographics of the two groups were similar. Both drugs
      provided, for the majority of patients, adequate pain relief as measured on a
      visual analog scale (VAS) completed every 15 minutes from T = 0 minutes to T = 45
      minutes. The average pain relief over 45 minutes (delta VAS) for CPZ was 4.87 cm,
      vs 4.34 cm for MC (p = 0.35). There also was no statistically significant
      difference in blood pressure (BP) changes (delta BP < 2 mm Hg for both systolic
      and diastolic BPs, p = 0.47 and 0.33) or numbers of patients reporting adverse
      effects (AEs) (CPZ: 16 of 35; MC: 13 of 29, p = 0.43). There was no severe AE
      with either study drug. CONCLUSIONS: Metoclopramide and chlorpromazine
      administered IV are both effective in the management of acute migraine headache.
      They are associated with similar minor side-effect profiles.

PMID- 8521206
TI  - Effect of continuous quality improvement methods on reducing triage to
      thrombolytic interval for acute myocardial infarction.
AB  - OBJECTIVES: To assess the timeliness of thrombolytic therapy in the ED for
      selected patients with acute myocardial infarction (AMI) following continuous
      quality improvement (CQI) interventions. METHODS: A retrospective, historical
      comparison study was performed of triage-to-thrombolytic time intervals for AMI
      patients using chart review for data collection. Patients treated after
      implementation of the CQI process vs a historical control group were compared.
      The patients with AMI who had received thrombolytics during the one-year period
      prior to the CQI interventions and who had documentation of time intervals served
      as the control group. The patients treated during a four-month period, beginning
      about one and a half years following introduction of the CQI interventions,
      served as the intervention group. Interventions included: a triage protocol, CQI
      review, and staff feedback. RESULTS: The mean triage-to-thrombolytic interval was
      longer for the control group (72 +/- 25 vs 40.0 +/- 22 min; p < 0.0001). The mean
      triage-to-ECG interval also was longer for the control group (16.5 +/- 8.9 vs 8.5
      +/- 7.5 min; p < 0.0001). Most (79%) of the study group received thrombolytic
      therapy within 60 minutes, and 39% within 30 minutes, whereas 39% of the control
      group received thrombolytic therapy within 60 minutes, and 3% within 30 minutes.
      CONCLUSION: The implementation of CQI techniques, including 100% chart review,
      intensive systems analysis, and staff feedback, had a positive effect on the
      timeliness of thrombolytic therapy for the ED patients who had AMI. As a result,
      most (79%) of the patients received therapy within the 60-minute time window
      recommended currently by the American Heart Association.

PMID- 8521207
TI  - Visualization of C7-T1 on portable lateral cervical spine radiographs using a
      lead-lined acrylic filter.
AB  - OBJECTIVE: To determine whether lead-lined acrylic cervical filters can improve
      the quality of portable lateral cervical spine (c-spine) radiographs for trauma
      patients. METHODS: Twenty trauma patients who required portable c-spine x-rays
      had these taken with a lead filter attached to the collimator of the portable x
      ray machine to improve penetration and visualization of lower cervical structures
      without overpenetrating upper cervical structures. The radiographs of these
      patients were compared with the first portable c-spine radiographs without
      filters for 20 controls matched for gender and injury severity. The comparison of
      radiographs was done by an experienced emergency physician and a neuroradiologist
      blinded to whether the filter was used. RESULTS: The two groups were similar for
      demographic and clinical characteristics. There was a significant improvement in
      the ability to visualize the C7-T1 level for the filter group compared with the
      control group (65% vs 30%, p < 0.05). Agreement between the physicians was
      excellent (kappa = 0.79, 95% CI = 0.60-0.99). CONCLUSIONS: Lead-lined acrylic
      filters improve the ability to visualize the lower c-spine in trauma patients.

PMID- 8521208
TI  - Accuracy of e-codes assigned to emergency department records.
AB  - OBJECTIVE: To determine the accuracy of ICD-9-CM external-cause-of-injury codes
      (e-codes) assigned to the medical records of injured patients treated in an ED
      and released. METHODS: A comparison was made of routine coding and expert
      recoding of medical records generated in the ED for a convenience sample of
      patients treated for injuries within 24 hours of injury occurrence and
      subsequently released from the ED. The medical record was handwritten and
      subsequently coded by three medical records coders (MRCs). The e-coded charts
      were sent to an external medical record consultant (expert), who was blinded to
      the codes previously assigned. The expert reading was used as the criterion
      standard. Accuracy was measured using a kappa statistic, and errors were
      described. RESULTS: Of 126 available patient charts, 108 (85.7%) were assigned e
      codes by MRCs. The expert assigned two codes to (double-coded) 67 patients, while
      the MRCs double-coded only one patient. The additional code was usually a "place
      of occurrence code." In 60 cases (55.6%), the expert code exactly matched the MRC
      code; kappa = 0.462. Of the 48 mismatches (44.4%), 20 (41.7%) were e-coded in the
      wrong category, 20 (41.7%) were e-coded in the correct category but with
      incorrect specificity of information, either too specific or not specific enough,
      and eight (16.6%) had combined coding errors. CONCLUSION: The accuracy of e-codes
      assigned to ED records was moderate in this single institution analysis. Errors
      were predominantly related to the specificity of the code, but some e-codes were
      in the wrong category. There are implications for injury surveillance and
      research. E-code assignment must be standardized and applied uniformly to obtain
      accurate codes. Automation of e-coding could improve accuracy and consistency of
      codes. National and international epidemiologic studies of cause of injury among
      ED patients will be severely hampered until e-code assignment can be better
      standardized.

PMID- 8521210
TI  - Emergency procedures important to the training of emergency medicine residents:
      who performs them in the emergency department?
AB  - OBJECTIVE: To quantify one aspect of emergency medicine (EM) training by
      determining the proportion of emergency procedures performed by emergency
      physicians (EPs) in EDs with EM residency programs (EMRPs). METHODS: Cross
      sectional descriptive survey of all allopathic EMRPs accredited by the EM
      Residency Review Committee (RRC-EM) as of July 1, 1993. Using a modified visual
      analog scale, program directors indicated the proportion of ten index procedures
      performed in the ED by EPs vs all other physicians. RESULTS: All 98 EMRPs meeting
      entry criteria responded to the survey. The medians for the percentage of times
      index procedures were performed in the ED by an EP were as follows (parentheses
      following percentages enclose 95% CIs): endotracheal intubation, 97% (95%, 100%);
      reduction of anterior shoulder dislocation, 93% (88%, 97%); thoracostomy, 63%
      (50%, 75%); transvenous pacer insertion, 60% (50%, 75%); cricothyrotomy, 50%
      (50%, 75%); thoracotomy, 50% (25%, 50%); diagnostic peritoneal lavage, 50% (25%,
      50%); fiberoptic laryngoscopy, 22% (6%, 25%); sigmoidoscopy, 0% (0%, 6%); and
      pelvic sonography, 0% (0%, 0%). CONCLUSION: EPs in EDs of institutions that have
      EMRPs perform, on average, 50% of all index procedures (95% CI 47%, 52%). This
      information may assist EM programs experiencing difficulty in ensuring that their
      residents receive an equitable share of those procedures that are critical to
      their training.

PMID- 8521209
TI  - Physical diagnosis skills of physicians in training: a focused assessment.
AB  - OBJECTIVE: To assess the proficiency of emergency medicine (EM) trainees in the
      recognition of physical findings pertinent to the care of the critically ill
      patient. METHODS: Fourteen medical students, 63 internal medicine (IM) residents,
      and 47 EM residents from three university-affiliated programs in Philadelphia
      were tested. Proficiency in physical diagnosis was assessed by a multimedia
      questionnaire targeting findings useful in emergencies or related to diseases
      frequently encountered in the ED. Attitudes toward diagnosis not based on
      technology, teaching practices of physical examination during EM training, and
      self-motivated learning of physical diagnosis also were assessed for all the EM
      trainees. RESULTS: With the exception of ophthalmology, the EM trainees were
      never significantly better than the senior students or the IM residents. They
      were less proficient than the IM residents in cardiology, and not significantly
      different from the IM residents in all other areas. For no organ system tested,
      however, did they achieve less than a 42.9% error rate (range: 42.9-72.3%, median
      = 54.8%). There was no significant improvement in proficiency over the three
      years of customary EM training. The EM residents who had received supervised
      teaching in physical diagnosis during training achieved a significantly higher
      cumulative score. The EM residents attributed great clinical importance to
      physical diagnosis and wished for more time devoted to its teaching. CONCLUSIONS:
      These data confirm the recently reported deficiencies of physical diagnosis
      skills among physicians in training. The results are particularly disturbing
      because they relate to EM trainees and concern skills useful in the ED. Physical
      diagnosis should gain more attention in both medical schools and residency
      programs.

PMID- 8521211
TI  - Delayed subluxation of an occult traumatic odontoid fracture in an elderly
      patient.
AB  - The issue of whether a traumatic but occult cervical spine fracture can exist has
      generated significant debate in emergency medicine. The profound clinical and
      legal implications of missing an unstable cervical spine injury are well known to
      the emergency care provider. An elderly patient who satisfies all of the rigorous
      criteria for this type of injury is discussed. The patient experienced delayed
      subluxation of her acute odontoid fracture during a flexion/extension examination
      completed in the ED, with resultant development of cervical discomfort. Elderly
      victims of trauma with an appropriate mechanism of injury should be suspected of
      subtle or occult neck injuries.

PMID- 8521212
TI  - Emergency management of blunt testicular trauma.
AB  - OBJECTIVE: Severe blunt testicular trauma is an infrequently reported consequence
      of injury, yet it is associated with significant sequelae. This case series
      evaluates the characteristics of patients with severe blunt testicular trauma,
      assesses the role of ultrasonography in their management, and offers an
      evaluation algorithm for use by both emergency and urology personnel. METHODS: A
      retrospective review was conducted of ten patients who had severe blunt
      testicular injuries referred for urologic evaluation over a seven-year period at
      a level 1 trauma center. Attention was focused on ultrasonographic results,
      operative findings, and testicular salvage rates. RESULTS: With the exception of
      two motorcycle crash victims, patients presented in a delayed fashion (mean 3.5
      days; range 1-5 days). Most (6/10) patients had true testicular rupture, all were
      explored urgently, and there was a 100% testicular salvage rate. Of the eight
      patients who had preoperative ultrasonographic examination, two were reported to
      show testicular rupture, but on exploration only one in fact had a tunica
      albuginea tear. Six patients had ultrasonographic examinations that revealed
      nonspecific abnormalities but failed to show testicular rupture; three had
      testicular rupture. CONCLUSIONS: Ultrasonography cannot be relied on to
      accurately diagnose rupture of the testis in high-risk patients. However,
      testicular rupture is universally associated with an abnormal ultrasonography
      scan, albeit commonly yielding nonspecific findings. A high level of suspicion is
      mandatory with high-energy transfer mechanisms. Since a significant delay in
      presentation is not unusual, early exploration is warranted in the setting of
      high risk and provides an excellent chance of testicular salvage. Injuries
      associated with normal testicular ultrasonography may be managed conservatively.

PMID- 8521213
TI  - Ultrasonography to evaluate adults for appendicitis: decision making based on
      meta-analysis and probabilistic reasoning.
AB  - OBJECTIVES: To review ultrasonography (US) test performance and to develop
      recommendations for the use of US to aid in the evaluation of potential
      appendicitis. METHODS: A meta-analysis was conducted using all English-language
      articles published since 1986 (17 studies; 3,358 patients) to ascertain
      sensitivity and specificity of US for diagnosing appendicitis in adults and
      teenagers. Calculation of the predictive value of US was performed for three
      groups of patients: group I--usually operated on (prevalence of appendicitis =
      80%); group II--usually observed in hospital (prevalence = 40%); and group III-
      usually released home (prevalence 2%). RESULTS: Overall sensitivity was 84.7%
      (95% CI: 81.0-87.8%), and specificity 92.1% (88.0-95.2). The accuracy and
      usefulness of US were related to the likelihood of appendicitis. In group I, a
      positive test was accurate [positive predictive value (PPV) = 97.6%], but a
      negative study could not rule out appendicitis [negative predictive value (NPV) =
      59.5%]. The converse was true for group III patients (PPV = 19.5%, NPV = 99.7%).
      Test performance accuracy was balanced only for group II patients (PPV = 87.3%,
      NPV = 89.9%). CONCLUSIONS: 1) US should not be used to exclude appendicitis for
      patients who have "classic" signs/symptoms, due to the underlying high false
      negative rate. 2) US is most useful for patients who have an indeterminate
      probability of disease after the initial evaluation--if US is positive, the
      patient should have an operation; otherwise, he or she should be observed. 3) US
      is not recommended for screening patients who have a low probability of
      appendicitis, due to the low prevalence of disease and high false-positive rate
      in this group.

PMID- 8521215
TI  - A wise fisherman and a young boy.

PMID- 8521214
TI  - Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis.
AB  - PURPOSE: To determine whether inhaled ipratropium bromide provides an additive,
      clinically important improvement in children with acute asthma who are being
      treated with beta 2-agonists. METHODS: An English-language literature search was
      conducted employing MEDLINE (1966 to 1992), Science Citation Index (1986 to 1992)
      using key citations, bibliographic reviews of primary research and review
      articles, and correspondence with authors of recent articles. After independent
      review by two observers, six studies were selected on the basis of prespecified
      selection criteria. Two observers independently assessed the selected papers by
      using explicit methodologic criteria for evaluating the quality of studies
      dealing with therapeutic intervention. RESULTS: None of the six studies found a
      significant difference in clinical rating score, admission rate, or length of
      stay in hospital between the ipratropium bromide and the control groups. The
      three studies with the highest methodologic validity measured the change in
      percentage predicted forced expiratory volume in 1 second (FEV1) from baseline to
      60 minutes. The pooled effect size (95% CI) for these studies was 0.88 (0.42
      1.34), which translates to an improvement in percentage predicted FEV1 over the
      control group of 12.5% (95% CI, 6.6-18.4). In a subset of 23 children who had
      severe airway obstruction, peak expiratory flow rate (PEFR) responded better to a
      beta 2-agonist alone (p = 0.007). CONCLUSION: The existing evidence reveals that
      the addition of ipratropium bromide to a beta 2-agonist offers a statistically
      significant improvement in percentage predicted FEV1 but no clinical improvement.
      As it may cause deterioration in PEFR in severely asthmatic children, ipratropium
      bromide should not be used universally for acute childhood asthma until further
      research determines the clinical significance of these spirometric changes.

PMID- 8521216
TI  - Propofol for conscious sedation: a case series.

PMID- 8521217
TI  - Ruptured splenic artery aneurysm.

PMID- 8521218
TI  - Colloid vs crystalloid.

PMID- 8521219
TI  - Pediatric emergency medicine training.

PMID- 8521220
TI  - [The analysis of the gastric mucosa by computerized densitometry].
AB  - An analytical method of histologic imaging of the gastric mucosa by computerized
      densitometry based on the extraction of components of an image on the basis of
      its luminous density is described. A group of 10 healthy controls, a group of 10
      subjects with gastric ulcer and 10 with duodenal ulcer were included in the
      study. The method was particularly useful in the identification of atrophic and
      hypertrophic processes. A decrease was found in the density of parietal and chief
      cells in atrophic gastritis of the gastric body. In atrophic gastritis of the
      gastric antrum a decrease was observed in global cell density of the antrum.
      Patients with gastric ulcer did not present variations versus the control group.
      In those with duodenal ulcers an increase was observed in the density of surface
      cell of the gastric body with no variation in the density of parietal and
      principal cells. This finding challenges the classical concept on the increase in
      parietal cell mass accompanying duodenal ulcers.

PMID- 8521221
TI  - [Carcinoma in situ of the gallbladder. The prognostic and therapeutic
      implications].
AB  - We have studied samples from gallbladders of five patients with carcinoma in situ
      over a 6-year period. Two were men and three women with du age ranging between 38
      and 68 years (mean age 56). The microscopic criteria employed for the diagnosis
      of carcinoma in situ were pseudostratification of the epithelium, nuclear
      crowding, loss of cell polarity, atypical mitotic divisions and absence of
      stromal invasion. Cholecystectomy was carried in all patients due to
      cholelithiasis. Signs and symptoms were those related to the presence of stones
      and none of the patients was the presence of carcinoma suspected clinically. All
      patients are alive and symptom-free 14-84 months after surgery. Authors concluded
      that patients with carcinoma in situ of the gallbladder usually follows a good
      course after cholecystectomy.

PMID- 8521222
TI  - [Congenital intrahepatic venous shunt as a cause of hepatic encephalopathy].
AB  - Macroscopic intrahepatic portosystemic shunts are extremely rare and may be due
      to liver injury, congenital vascular malformations or pathologic collaterals
      secondary to portal hypertension. Forty-eight cases have been reported in the
      literature up to 1994 with 50-60% presenting cerebral manifestations and 40%
      being associated with cirrhosis. The case of a patient without cirrhosis who was
      admitted for upper digestive hemorrhage secondary to gastroduodenal ulcer is
      described. At 48 hours the patient had an episode of hepatic encephalopathy
      coinciding with bleeding reactivation. Abdominal echography suggested
      communication between the right portal and suprahepatic veins and posterior
      angiography confirmed the diagnosis. Color Doppler echography determined shunt
      and portal vein blood flow. No case of intrahepatic portosystemic venous shunt as
      a cause of encephalopathy was found to have been reported in the Spanish
      literature.

PMID- 8521223
TI  - [Epithelioid hemangioendothelioma localized in the small intestine].
AB  - Epithelioid hemangioendothelioma is a unique tumor of adult life which is
      characterized by epithelioid or histiocytoid endothelial cells. These tumors are
      rare, and developed preferentially in the dermis and subcutaneous tissues of the
      distal extremities. They grow in a slowly progressive fashion, have a borderline
      biological behavior, and a good response to surgical treatment. The authors
      present a 63-years-old woman with an epithelioid hemangioendothelioma localized
      in small intestine. The patient had a history of abdominal pain and recurrent
      rectal bleeding being surgically treated.

PMID- 8521224
TI  - [A functioning carcinoid tumor with liver involvement without the associated
      carcinoid syndrome].
AB  - The carcinoid tumor, the most frequent variety of the neuroendocrine or amine
      precursor uptake and decarboxylation (APUD) tumors, typically produces biogenic
      amines and polypeptide hormones and occasionally gives rise to a striking
      clinical presentation called carcinoid syndrome. The severity of this syndrome is
      directly related to the tumor bulk draining into the systemic circulation. This
      implies almost always hepatic metastases. We present a case in which a carcinoid
      tumor with extensive hepatic involvement and remarkable biologic activity did not
      produce any clinical features of the carcinoid syndrome. We believe that such a
      case enlightens the clinical and biochemical complexity of this entity.

PMID- 8521225
TI  - [Toxic cholestatic hepatitis due to phenytoin].
AB  - We report the case of a 51-years-old female who was prophylactically treated with
      diphenylhydantoin after surgery of an intracranial aneurysm. Twenty-four days
      after beginning the treatment, a general syndrome appeared, in addition to a
      diffuse cutaneous exanthema. Four days later, a cholestatic syndrome, compatible
      with "toxic cholestatic acute hepatitis", was developed. The suppression of the
      drug, was followed by rapid clinical improvement and gradual normalization of
      transaminases values, although biochemical cholestasis persisted for months.

PMID- 8521226
TI  - [Streptococcus bovis in a surgical wound and a colonic neoplasm].
AB  - The association of colorectal carcinoma and septicemia or endocarditis by
      Streptococcus bovis is well known. Nonetheless, other localizations of infection
      by Streptococcus bovis have not been associated with colorectal carcinoma. The
      case of association of colon neoplasm with infection by Streptococcus bovis
      localized in the surgical wound of resection of a prostate adenoma by the
      transvesical route carried out four months previously is presented. Possible
      intraoperative bacteremia colonizing the surgical wound due to colic compression
      during surgery may have been the cause. This localization of infection by
      Streptococcus bovis should be taken into account in screening of colorectal
      carcinoma.

PMID- 8521227
TI  - [Natriuretic peptides and the homeostasis of renal circulation in cirrhosis].

PMID- 8521228
TI  - [Familial amyloidotic polyneuropathy and liver transplantation].

PMID- 8521229
TI  - [New technical aspects in liver transplantation. The preservation of the vena
      cava of the recipient].

PMID- 8521230
TI  - [Vasodilators and renal function in cirrhosis].

PMID- 8521231
TI  - [Dieulafoy lesions].

PMID- 8521232
TI  - [The endoscopic finding of a worm in the cecal region of an asymptomatic
      patient].

PMID- 8521233
TI  - Use of chemotherapy to cure head and neck cancer.

PMID- 8521234
TI  - Taxol plus radiation for head and neck cancer.
AB  - Taxol (paclitaxel) is the prototype of a new class of cancer drugs, the taxanes.
      This group of anticancer agents have a novel mechanism of action, broad clinical
      activity, and potential as clinical radiosensitizers. Paclitaxel may be the most
      efficacious single chemotherapy agent for head and neck cancer with a 40%
      response rate for patients with recurrent disease. As it is possible to achieve
      durable control with radiotherapy of locally advanced head and neck cancer in
      only a minority of cases, chemotherapy drugs such as paclitaxel are being used
      with radiotherapy in an attempt to improve tumor control. Paclitaxel stabilizes
      microtubules and leads to accumulation of cells at the G2/mitosis phase of the
      cell cycle, which is a necessary condition for its antitumor effect, and also the
      phase with the greatest relative radiosensitivity. Paclitaxel has been shown to
      be a radiosensitizer in vitro for some but not all cell lines studied. In vitro
      dose-response data for paclitaxel paradoxically suggest that prolonged exposure
      to relatively low concentrations--those easily achievable clinically--may be more
      effective than higher doses both for direct cytotoxicity and radiosensitization.
      These data suggest that paclitaxel has potential as a clinical radiosensitizer
      for head and neck cancer, and phase I trials are in progress. We review the
      laboratory and clinical studies supplying the rationale, risks, and potential
      benefits for the concurrent use of paclitaxel and radiotherapy, the current
      investigational clinical trials, including our NCI-sponsored phase I trials with
      continuous infusion paclitaxel as a potential radiosensitizer for head and neck
      cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521235
TI  - 5-fluorouracil plus radiation for head and neck cancer.
AB  - 5-fluorouracil is a widely used chemotherapeutic agent. Its role and activity in
      the treatment of squamous cell carcinoma of the head and neck are reviewed. In
      head and neck cancer, 5-fluorouracil is mostly used in combination with
      cisplatin. Despite a high activity of this regimen, as documented in response
      rates of up to 90%, its use as an adjuvant to surgery and radiation does not
      impact consistently on survival rates. In contrast, 5-FU-based chemotherapy with
      concomitant radiotherapy seems to improve treatment outcome. Several randomized
      trials suggest improved locoregional control with concomitant chemoradiotherapy
      with a 5-fluorouracil-based chemotherapy regimen. The activity and the metabolism
      of 5-FU can be further modulated by cisplatin, hydroxyurea, and leucovorin.

PMID- 8521236
TI  - Cisplatin plus radiation therapy.
AB  - Advanced-stage squamous cell cancer of the head and neck remains a difficult
      therapeutic dilemma despite aggressive use of surgery and radiation therapy. The
      majority of patients still relapse with locoregional disease. Distant metastases
      are a frequent cause of failure in patients where local disease is controlled.
      Neoadjuvant chemotherapy reduces the incidence of distant metastasis, but despite
      the promise generated by a high objective response rate, does not alter the
      frequency of local recurrence or improve patient survival. The concomitant use of
      chemotherapy and radiation therapy has the theoretical advantage of
      radiosensitization with improved local control, preservation of the systemic
      effect of neoadjuvant treatment, and reduction in the total treatment time.
      Clinical trials conducted using cisplatin alone or in combination with 5
      fluorouracil strongly suggest that this local control advantage is achieved. But
      randomized studies, convincingly demonstrating that the increased toxicity
      observed with most concomitant programs is justified by increased patient
      survival compared with radiation therapy alone, have yet to be completed. Future
      trials will need to evaluate the impact of cisplatin dose and route of
      administration. The incorporation into concomitant treatment programs of new
      agents recently demonstrated as active in head and neck cancer also deserves
      aggressive clinical investigation.

PMID- 8521237
TI  - 5-fluorouracil by protracted subcutaneous infusion. A pilot study.
AB  - A feasibility study of 5-fluorouracil (5-FU) delivered by long-term subcutaneous
      infusion (SCI) was carried out in 10 patients with advanced malignancies
      refractory to conventional treatment. 5-FU: 200 mg/m2/day was administered by an
      external infusor (Baxter 5 or 7 Multiday) connected with a 21-gauge needle placed
      in the thoracic wall. Treatment was continued until progression of disease or
      toxicity. WHO grade II to III mucositis was experienced by two and one patients,
      respectively. Grade II diarrhea developed in one patient. Local toxicity was
      substantial but painless and manageable; skin ulceration was experienced by two
      patients. A total of 88 weeks of therapy was delivered with a median of 8.8 weeks
      for each patient (range 2 to 16). Two patients (breast and colorectal cancer)
      achieved a partial remission; two additional cases showed a > 50% decrease in
      tumor marker levels. In conclusion, the administration of 5-FU by SCI deserves
      further evaluation, especially in clinical circumstances in which venous access
      is limited by thrombosis or technical concerns.

PMID- 8521238
TI  - Etoposide plus cisplatin followed by thoracic radiation for stage IIIB non-small
      cell lung cancer: MAOP study 2188.
AB  - Thirty-five patients with stage III B non-small cell lung cancer were treated
      with the combination of cisplatin (CDDP) 30 mg/M2/day and etoposide (VP16-213) 75
      mg/M2/day administered as a 72-hour infusion. Twenty evaluable patients (67%)
      received subsequent thoracic radiation as definitive regional therapy following a
      clinical response or stable disease status. Complete plus partial responses to
      chemotherapy were observed in 15 patients (5CR and 10PR or 44%). Of the 20
      patients who received radiation, six responded with five transitioning from
      stable disease to partial (2) or complete (3) responses. The overall response
      rate to the combined sequential chemotherapy plus radiation was therefore 20/35
      or 59% with eight complete responders. Histopathology influenced the response
      rate to chemotherapy (53% versus 30% for epidermoid versus adenocarcinomas,
      respectively), but following radiation, the response rates were similar for the
      two pathologic subtypes (73% versus 71%). Median overall survival was 363 days
      with 20% of patients alive at 13 to 45 months. The response rate for CDDP plus
      VP16-213 chemotherapy administered as a 72-hour infusion was superior for stage
      III B non-small cell lung cancer compared with stage IV disease as previously
      reported by the Mid Atlantic Oncology Program (44% versus 25%). This difference
      between stage III B and stage IV was also reflected in median survival (363 days
      versus 190 days). The sequential addition of radiation therapy to this
      chemotherapy regimen is feasible in stage III B disease with a small proportion
      of patients demonstrating long-term survival.

PMID- 8521239
TI  - Administration of high-dose tumor necrosis factor alpha by isolation perfusion of
      the limbs. Rationale and results.
AB  - Recombinant tumor necrosis factor alpha (rTNF alpha) has potent antitumor
      activity in experimental studies on human tumor xenografts. However, in humans,
      the administration of rTNF alpha is hampered by severe systemic side effects. The
      maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold
      less than the effective dose in animals. Isolated perfusion of the limbs (ILP)
      allows the delivery of high-dose rTNF alpha in a closed system with acceptable
      side effects. A protocol with a triple-drug regimen was based on the reported
      synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with
      hyperthermia. In patients with melanoma-in-transit metastases (stage IIIA or AB),
      we obtained a 91% complete response rate compared with 52% after ILP with
      melphalan alone. In unresectable soft tissue sarcomas, this protocol was found to
      produce a 50% complete response with 87.5% limb salvage, since most tumors became
      removable. Release of nanograms levels of TNF alpha in the systemic circulation
      was evident, but control of this leakage and appropriate intensive care resulted
      in acceptable toxicity. Angiographic, immunohistological, and immunological
      studies suggest that the efficacy of this protocol is due to a dual targeting:
      rTNF alpha activates and electively lyses the tumor endothelial cells, while
      melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to
      be a useful model for studying the biochemotherapy of cancer in man.

PMID- 8521240
TI  - Formal clinical evaluation of the CADD-Micro system for circadian delivery of
      FUDR in patients with metastatic renal cell cancer.
AB  - The CADD-Micro System (Sims Deltec, St. Paul, MN) was formally evaluated in
      patients with metastatic renal cell cancer, participating in a phase-III study
      comparing a 2-week circadian versus flat infusion of FUDR. Ten patients
      participated, 2 receiving five cycles of FUDR by a flat infusion, and 8 receiving
      12 cycles of FUDR by circadian infusion. A total of 235 treatment days were
      evaluated. All patients had a Port-A-Cath in place for venous access. The
      patients completed a structured evaluation survey for each week of treatment
      regarding their interaction with the pump and an overall evaluation of the system
      and the patient information guide at the end of each 2-week course. Nurses from
      our home infusion program completed a separate evaluation. Overall patient and
      clinician perception of this pump was excellent. The main drawback had to do with
      the design of the battery compartment cover and the handling of the drug
      reservoir. The small size of the drug reservoir (10 mL) limits the usability of
      this pump to low-volume tasks.

PMID- 8521241
TI  - Effects of toxin Ts-gamma and tityustoxin purified from Tityus serrulatus
      scorpion venom on isolated rat atria.
AB  - The effects of toxin Ts-gamma and tityustoxin purified from Tityus serrulatus
      scorpion venom were investigated on isolated rat atria. Rat atria were placed in
      an organ bath containing Krebs-Ringer solution, 30 degrees C, pH 7.4, and bubbled
      with a gas mixture of 95% O2 and 5% CO2. The atrial rate and contractile force
      were simultaneously recorded. Addition of toxin Ts-gamma to the bath (0.14
      microM) evoked an initial reduction of both atrial rate and contractile force,
      followed by a small increase in force and a decrease in rate, and finally a long
      reduction of rate and force. Addition of an identical dose of Ts-gamma 30 or 60
      min later did not evoke any effect. Addition of tityustoxin to the bath (0.14
      microM) induced an increase of atrial rate and force. Addition of an identical
      dose of tityustoxin 30 min later evoked similar effects. The negative
      chronotropic and inotropic effects induced by Ts-gamma were abolished by
      tetrodotoxin (TTX, 1 microM) or atropine (1.5 microM), whereas the positive
      effects observed in the presence of atropine were prevented by TTX (1 microM) or
      alprenolol (10 microM). The negative chronotropic effect of 0.14 microM
      tityustoxin was only observed in the presence of physostigmine (0.3 microM). This
      negative effect was abolished by TTX (1 microM) or atropine (1.5 microM). The
      positive inotropic effect of tityustoxin was decreased by TTX (1 microM and 10
      microM), but was totally prevented by guanethidine (10 microM) or alprenolol (10
      microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521242
TI  - In vivo and in vitro effects of graded doses of the pesticide heptachlor on
      female sex steroid hormone production in rats.
AB  - Adult female Sprague-Dawley rats were injected with corn oil or 5 mg, 20 mg, 25
      mg or 30 mg per kg body weight of heptachlor solution every other day for up to
      18 days. The rats were killed at the end of the experimental period, and blood
      samples were assayed for progesterone and oestrogen by radioimmunoassay. Ovarian
      cells from the rats were isolated and incubated either on their own, or in the
      presence of LH or FSH, and production of progesterone and oestrogen determined.
      Control incubations consisted of cells from corn oil-treated rats. The latter
      were also incubated on their own or in the presence of LH or FSH. Heptachlor
      significantly suppressed blood progesterone and oestradiol levels (P < 0.05 to P
      < 0.001), the degree of suppression depending on the dose and the stage of the
      oestrous cycle in which samples were obtained. Production of oestradiol by
      ovarian cells from heptachlor-treated rats was lower than for corn oil-treated
      controls. Cells from rats treated with low doses of heptachlor (5 mg per kg body
      weight) showed an increased production of progesterone, while high doses (> 20 mg
      per kg body weight) suppressed production.

PMID- 8521243
TI  - Evidence for the involvement of opioid peptides in phagocytosis, conformation,
      granulation and aggregation of immunocompetent Lumbricus terrestris amoebocytes.
AB  - Opioid peptides and their analogs were shown to enhance Lumbricus terrestris
      amoebocyte phagocytosis, aggregation, granulation and conformation. These actions
      appear to be concentration dependent with 10(-8) M met-enkephalin and 10(-6) M
      dynorphin A having the greatest effect on the earthworm amoebocytes (P < 0.05).
      Interleukin-1 alpha significantly enhanced met-enkephalin mediated earthworm
      amoebocyte aggregation; leu-enkephalin mediated phagocytosis and aggregation;
      DAMA mediated phagocytosis; and U69,593 mediated phagocytosis, aggregation and
      conformation (P < 0.05). Naloxone generally inhibited these activities indicating
      opioid receptor mediated mechanisms for earthworm amoebocyte function.

PMID- 8521244
TI  - Dexamethasone inhibits inorganic phosphate stimulated Ca(2+)-dependent damage of
      isolated rat liver and renal cortex mitochondria.
AB  - The prevention of Ca(2+)-induced permeabilization of rat liver and kidney cortex
      mitochondria by dexamethasone, a common anti-inflammatory glucocorticoid, was the
      subject of this study. A non-specific release of matrix Ca2+ and membrane
      depolarization was observed in respiring mitochondrial suspensions subjected to a
      30 nmol Ca2+/mg protein load in the presence of 2 mM inorganic phosphate (Pi), or
      20 nmol Ca2+/mg protein with 1 mM Pi, for liver and renal cortex mitochondria
      (RCM), respectively. Additions of dexamethasone prior to Ca2+ in mitochondrial
      suspensions from liver or kidney cortex (80 and 200 microM final concentrations,
      respectively) led to 75-80% protection from these permeabilization-associated
      alterations of functional integrity. In conclusion, dexamethasone appears to show
      great promise in blocking the opening of a Ca(2+)-dependent 'non-specific pore'
      in the inner membranes of mitochondria from various sources.

PMID- 8521245
TI  - Effect of acute and chronic glutathione depletion on renal function in the rat.
AB  - Renal function was evaluated in normal and acid-loaded rats following acute and
      chronic depletion of glutathione (GSH) by buthionine sulfoximine (BSO).
      Creatinine clearance and fractional excretion of electrolytes were normal. There
      was no acidification or concentration defect detected in animals with acute or
      chronic GSH depletion.

PMID- 8521246
TI  - Bilateral adrenalectomy induces early onset of summer fur growth in mink (Mustela
      vison).
AB  - The purpose of this study was to determine the effects of bilateral adrenalectomy
      on the time at which growth of the summer pelage begins in mink. Bilateral
      adrenalectomy of adult female mink between 2 and 11 March 1991, supplemented with
      deoxycorticosterone (DOC) as a mineralocorticoid, resulted in the onset of the
      summer fur growth approximately 5 weeks earlier than the controls (P < 0.01).
      Mink with their adrenal glands intact and treated with DOC, exhibited summer fur
      growth 2 weeks earlier than the controls (P < 0.01). The duration of time between
      the first observed hair growth and attainment of maximal guard hair length, was
      approximately 10 days longer in mink with their adrenal glands intact and
      supplemented with DOC than the controls (P < 0.05). Adrenalectomized mink treated
      with DOC exhibited guard hair growth for approximately 13 days longer than
      controls (P < 0.05). Although exogenous DOC initiated hair growth, the rate of
      growth appeared to be reduced. These data suggest that adrenal hormones, of
      undetermined identity, exert a tonic inhibitory effect on the initiation of
      summer fur growth in mink and may be part of the mechanism through which changes
      in photoperiod regulate the onset of hair growth cycles.

PMID- 8521247
TI  - Action of CCK on CDE diet-induced acute pancreatitis in rats treated with
      hydrocortisone.
AB  - The present work studies the effect of previous hydrocortisone administration (10
      mg/kg/day) over 7 days on the later development of diet-induced acute
      pancreatitis in the rat. Acute pancreatitis was induced by feeding a diet
      deficient in choline and supplemented with 0.5% ethionine (CDE diet) over 10
      days. Hydrocortisone pretreatment exacerbated CDE-induced acute pancreatitis.
      There was a significant increase in serum amylase, pancreatic edema, and
      haematocrit levels and an insignificant decrease in pancreatic mass in rats
      pretreated with hydrocortisone. Pancreatic enzyme secretion was strongly reduced
      in the rats subjected to acute pancreatitis, and although the drop in enzyme
      levels did not reach statistical significance, the values of secretion were even
      further reduced in the animals treated with hydrocortisone, pointing to the
      absence of pancreatic functionality. This effect can be attributed to enzyme
      storage elicited by previous hydrocortisone administration; activated
      intracellularly, these enzymes could aggravate the pathology. Administration of
      the cholecystokinin octapeptide (CCK-8) (10 micrograms/kg/day) during the
      development of acute pancreatitis in animals pretreated with hydrocortisone
      substantially improved the general state of the animals' pancreases. There was a
      significant decrease in serum amylase, pancreatic edema and haematocrit levels in
      rats injected with CCK, which was accompanied by an increase in pancreatic
      functionality. Conversely, the administration of L-364,718 (0.1 mg/kg/day), a CCK
      antagonist, did not improve pancreatic functionality and did not appreciably
      affect the general state of the organ. It is concluded that in rats with storage
      levels increased by hydrocortisone administration that are subjected to acute
      pancreatitis, the secretagogue effect of CCK is more beneficial than the repose
      of the gland induced by L-364,718.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521248
TI  - Biopotency of fetal bovine serum, and insulin and insulin-like growth factors I
      and II in enhancing whole-body protein synthesis of chicken embryos cultured in
      vitro.
AB  - Whole-body protein synthesis in chicken embryos was measured to examine the
      biopotency of fetal bovine serum, bovine insulin, recombinant human insulin, and
      recombinant human insulin-like growth factors (IGF) I and II. In all experiments
      chicken embryos at 7 days of incubation age were used and cultured in a synthetic
      serum-free medium in the presence or absence of the testing substances with a
      rotatory whole-embryo culture apparatus for up to 30 min. Whole-body protein
      synthesis was measured from the time course of specific radioactivities of free
      and protein-bound L-[4-3H]phenylalanine. In addition, the effect of bovine
      insulin on phenylalanine extraction rate from the culture medium was
      investigated. Supplementing the medium with fetal bovine serum and human IGF-I
      significantly enhanced whole-body protein synthesis. In contrast, human IGF-II,
      bovine insulin, or human insulin did not affect whole-body protein synthesis,
      although bovine insulin increased phenylalanine extraction rate from the culture
      medium in a proportional fashion as the dose increased. Therefore, from these
      results it was concluded that IGF-I, but not IGF-II, might be one of the anabolic
      factors in fetal bovine serum for stimulating whole-body protein synthesis, and
      that insulin may play a role in stimulating amino acid transport, but it may not
      be directly involved in protein synthesis of chicken embryos.

PMID- 8521250
TI  - Effects of the mammalian vasoconstrictor peptide, endothelin-1, on Tetrahymena
      pyriformis GL, and the immunocytological detection of endogenous endothelin-like
      activity.
AB  - The vasoconstrictor endothelin-1 (ET-1) is shown to have significant
      physiological effects on a unicellular organism, Tetrahymena pyriformis. These
      responses include: (1) A significant increase in intracellular [Ca2+] induced by
      10(-10) M ET-1; (2) Increased chemotaxis, maximal at 10(-10) M; and (3) A small
      inhibition of proliferation at the 10(-13)-10(-12) M concentration range.
      Immunocytochemical detection of endogenous ET-1 using rabbit antibodies directed
      against human or porcine ET-1 indicates that this is a further example of the
      widening group of vertebrate hormones now known to be synthesized by Tetrahymena.
      These observations suggest that hormones are of considerable antiquity in their
      phylogenetic appearance and have been highly conserved throughout evolution.

PMID- 8521249
TI  - Insulin and glucagon secretion in goats (Capra hircus Linnaeus) exposed to cold.
AB  - Cold exposure significantly decreased the insulin response to the intravenous
      injection of arginine, butyrate and tolbutamide, and tended to reduce the
      response to glucose in goats. The glucagon responses to these test materials were
      not different between warm and cold environments. Intravenous phentolamine
      infusion tended to increase, and propranolol infusion decreased insulin secretion
      more effectively in the cold than in the warm environment. It is concluded that
      cold exposure decreases insulin secretion in response to a variety of stimuli in
      goats.

PMID- 8521251
TI  - Hypolipidemic agents alter hepatic mitochondrial respiration in vitro.
AB  - The direct effects of three different classes of structurally diverse
      hypolipidemic agents on respiration were studied in mitochondria isolated from
      donor Sprague-Dawley rats. Two classes of peroxisome proliferators (i.e.
      plasticizers and hypolipidemic hormones and drugs) and one class of peroxisome
      inhibitors (i.e. anti-psychotic drugs) were studied. The phthalate ester
      plasticizers dibutylphthalate, ethylhexanoic acid and di(2-ethylhexyl) adipate,
      the hypolipidemic hormones or drugs dehydro-epiandrosterone (DHEA), thyroxine
      (T4), triiodothyronine (T3), gemfibrozil, clofibrate and naphthoflavone, and the
      anti-psychotic drugs chlorpromazine, thioridazine and fluphenazine were studied.
      As the dose of the plasticizer dibutylphthalate increased from 8 to 200 mumol/l,
      there was a decrease (P < 0.05) in state 3 (+ADP) respiration and in the
      respiratory control ratio for both substrates tested. The anti-psychotic drug
      chlorpromazine decreased state 3 malate + pyruvate-supported respiration and
      increased state 3 succinate-supported respiration. As the concentration of all
      three anti-psychotic drugs increased, there was a linear increase in state 4
      respiration (-ADP) and a decrease in the respiratory control ratio for both
      substrates tested. As the dose of the hypolipidemic agents DHEA, gemfibrozil and
      T4 increased, there was a linear reduction in state 3 malate + pyruvate-supported
      respiration. However, when succinate was used as the substrate to support
      respiration, only the thyroid hormones significantly decreased state 3
      respiration. Gemfibrozil, T4 and T3 increased state 4 respiration, regardless of
      the substrate used. As the dose of clofibrate, gemfibrozil, and the thyroid
      hormones increased, there was a linear reduction in the respiratory control ratio
      for both substrates tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521252
TI  - Toxicity and excretion of cisplatin in the avian kidney.
AB  - Cisplatin is a widely applied antineoplastic drug with significant nephrotoxic
      potential. The purpose of this study was to define the toxic effect and excretion
      of cisplatin in the chicken, a species widely applied to the study of tubular
      transport mechanisms but little used for toxicology studies. Toxicity was
      assessed by the relative effect of cisplatin on renal clearances of the standard
      reference substrates inulin and p-aminohippurate (PAH) and by morphologic
      assessment of the kidneys of cisplatin-treated chickens. The data clearly support
      close similarities in the pattern of tubular cell damage produced in the chicken
      versus that reported for rats and human patients. It was further demonstrated
      that administration of an organic cation reduced Pt accumulation in the kidney
      and mitigated the toxicity as has been reported for rats. Excretion studies were
      carried out during unilateral renal portal infusion of cisplatin, and the results
      indicated that cisplatin does not undergo net tubular secretion as occurs in the
      rat and human. It can be concluded that, while the pattern of cisplatin-induced
      nephrotoxicity closely parallels that seen in mammals, the avian kidney exhibits
      a different pattern of urinary Pt excretion than does the mammalian kidney after
      cisplatin administration.

PMID- 8521253
TI  - On the neurophysiology of consciousness: Part II. Constraining the semantic
      problem.
AB  - The main idea in this series of essays is that subjective awareness (more
      precisely, what I call C) depends upon the intralaminar nuclei of each thalamus
      (hereafter, ILN). This implies that the internal structure and external relations
      of ILN make subjective awareness possible. An array of material relevant to this
      proposal was briefly reviewed in Part I (Bogen, 1995). This Part II considers in
      more detail some semantic aspects and a bit of philosophic background as these
      pertain to propositions 0, 1, and 2 of Part I. Part II should be read in
      conjunction with Part I.

PMID- 8521254
TI  - Tutorial commentary: surprisingly small subcortical structures are needed for the
      state of waking consciousness, while cortical projection areas seem to provide
      perceptual contents of consciousness.
AB  - The evidence can therefore be summarized as follows: (1) RF, nRt, and ILN
      activity seem to be necessary but not sufficient for conscious experience. (2)
      Stimulus representation in primary sensory projection areas also seems to be
      necessary but not sufficient for conscious perceptual experience (Weiskrantz,
      1980). The simplest hypothesis is that both components are necessary and
      sufficient to support conscious perceptual experience.

PMID- 8521255
TI  - Visual awareness and the thalamic intralaminar nuclei.

PMID- 8521256
TI  - The intralaminar thalamic nuclei: subjectivity pumps or attention-action
      coordinators?

PMID- 8521257
TI  - Thalamic contributions to attention and consciousness.
AB  - A tacit assumption since the 19th Century has been that the neocortex serves as
      the "seat of consciousness." An unexpected challenge to that assumption arose in
      1949 with the discovery that high-frequency EEG activation associated with an
      alert state requires the intactness of the brainstem reticular formation. This
      discovery became the impetus for nearly three decades of research on what came to
      be known as the reticular activating system. By the 1970s, however,
      methodological and philosophical controversies led to the general abandonment of
      subcortical theories of attention and consciousness, with a return to an almost
      exclusive focus upon the cortex. With recent advances in the neurosciences the
      focus is shifting once more, this time to the unique contributions of cortical,
      thalamic, and brainstem structures in mediating selective attention and
      perceptual awareness. This paper offers a nontechnical review of the history of
      these developments up to contemporary interest in the putative role of
      oscillatory EEG patterns in the integration of perceptual features of experience.
      It puts forward the thesis that a key to understanding attention and
      consciousness is an appreciation of the contributions of the thalamus to these
      cognitive processes.

PMID- 8521258
TI  - Windows on animal minds.
AB  - The simple kinds of conscious thinking that probably occur in nonhuman animals
      can be studied objectively by utilizing the same basic procedure that we use
      every day to infer what our human companions think and feel. This is to base such
      inferences on communicative behavior, broadly defined to include human language,
      nonverbal communication, and semantic communication in apes, dolphins, parrots,
      and honeybees. It seems likely that animals often experience something similar to
      the messages they communicate. Although this figurative window on other minds is
      obviously imperfect, it is already contributing significantly to our growing
      understanding and appreciation of animal mentality.

PMID- 8521259
TI  - Using self-view television to distinguish between self-examination and social
      behavior in the bottlenose dolphin (Tursiops truncatus).
AB  - In mirror mark tests dolphins twist, posture, and engage in open-mouth and head
      movements, often repetitive. Because postures and an open mouth are also dolphin
      social behaviors, we used self-view television as a manipulatable mirror to
      distinguish between self-examination and social behavior. Two dolphins were
      exposed to alternating real-time self-view ("mirror mode") and playback of the
      same to determine if they distinguished between them. The adult male engaged in
      elaborate open-mouth behaviors in mirror mode, but usually just watched when
      played back the same material. Mirror mode behavior was also compared to
      interacting with real dolphins (controls). Mark tests were conducted, as well as
      switches from front to side self-views to see if the dolphins turned. They
      presented marked areas to the self-view television and turned. The results
      suggest self-examination over social behavior.

PMID- 8521260
TI  - Mirrors, minds, and cetaceans.

PMID- 8521261
TI  - Evidence of dolphin self-recognition and the difficulties of interpretation.

PMID- 8521262
TI  - Self-view television as a test of self-awareness: only in the eye of the
      beholder?

PMID- 8521263
TI  - Self-recognition in dolphins: credible cetaceans; compromised criteria, controls,
      and conclusions.

PMID- 8521264
TI  - The experience of self in the bottlenose dolphin.
AB  - Marten and Psarakos have presented some evidence which suggests that objective
      self-awareness and possibly representations of self may characterize the
      dolphins' experience of self. Their research demonstrates the possibility of
      similarities in the sense of self between primate species and dolphins, although
      whether dolphins have subjective self-awareness, personal memories, and theories
      of self--all important facets of the sense of self in humans--was not examined.
      Clearly, even this limited evidence was difficult to achieve; the difficulties in
      adapting methods and coding behavior are quite apparent in their report. Future
      progress, however, may depend upon clarification of what are the necessary
      components for a sense of self and an explication of how these might be reflected
      in dolphin behavior. We are mindful of the authors' point (pp. 219 and 220) that
      the dolphin lives more in an acoustic than a visual environment. Thus, while
      tasks relying upon vision may reveal the presence or absence of the sense of self
      in primates, it might well be the case that in dolphins self-related experiences
      might be better revealed in auditory tasks. But then, what is the nature of human
      self-awareness in terms of audition? While both conceptual and methodological
      hurdles remain, Marten and Psarakos have demonstrated that important questions
      can be asked about the minds and phenomenal worlds of nonanthropoid species.

PMID- 8521265
TI  - Reflections from reading the first sentence.

PMID- 8521266
TI  - "Is it live or is it Memorex?".

PMID- 8521267
TI  - Self-recognition in the bottlenose dolphin: ecological considerations.

PMID- 8521268
TI  - Marten and Psarakos commentary response.

PMID- 8521269
TI  - Evidence for consciousness.

PMID- 8521270
TI  - Fast algorithms for inferring evolutionary trees.
AB  - We present algorithms for the perfect phylogeny problem restricted to binary
      characters. The first algorithm is faster than a previous algorithm by Gusfield
      when the input matrix for the problem is sparse. Next, we present two online
      algorithms. For the first of these, the set of species is fixed and the
      characters are given as input one at a time, while, for the second, the set of
      characters is fixed and the species are given as input one at a time. These two
      online algorithms are then combined into an algorithm that can process any
      sequence of additions and deletions of species and characters.

PMID- 8521271
TI  - Analysis of tRNA gene sequences by neural network.
AB  - The quantitative similarity among tRNA gene sequences was acquired by analysis
      with an artificial neural network. The evolutionary relationship derived from our
      results was consistent with those from other methods. A new sequence was
      recognized to be a tRNA-like gene by a neural network on the analysis of
      similarity. All of our results showed the efficiency of the artificial neural
      network method in the sequence analysis for biological molecules.

PMID- 8521272
TI  - Exceptional motifs in different Markov chain models for a statistical analysis of
      DNA sequences.
AB  - Identifying exceptional motifs is often used for extracting information from long
      DNA sequences. The two difficulties of the method are the choice of the model
      that defines the expected frequencies of words and the approximation of the
      variance of the difference T(W) between the number of occurrences of a word W and
      its estimation. We consider here different Markov chain models, either with
      stationary or periodic transition probabilities. We estimate the variance of the
      difference T(W) by the conditional variance of the number of occurrences of W
      given the oligonucleotides counts that define the model. Two applications show
      how to use asymptotically standard normal statistics associated with the counts
      to describe a given sequence in terms of its outlying words. Sequences of
      Escherichia coli and of Bacillus subtilis are compared with respect to their
      exceptional tri- and tetranucleotides. For both bacteria, exceptional 3-words are
      mainly found in the coding frame. E. coli palindrome counts are analyzed in
      different models, showing that many overabundant words are one-letter mutations
      of avoided palindromes.

PMID- 8521273
TI  - Toward a characterization of landscapes of combinatorial optimization problems,
      with special attention to the phylogeny problem.
AB  - This article introduces a coherent language base for describing and working with
      characteristics of combinatorial optimization problems, which is at once general
      enough to be used in all such problems and precise enough to allow subtle
      concepts in this field to be discussed unambiguously. An example is provided of
      how this nomenclature is applied to an instance of the phylogeny problem. Also
      noted is the beneficial effect, on the landscape of the solution space, of
      transforming the observed data to account for multiple changes of character
      state.

PMID- 8521274
TI  - Identification of new members of a carbohydrate kinase-encoding gene family.
AB  - In a sequence database search using the human glycerol kinase-encoding sequence
      (HUMGLYKINB) as a query, we identified six previously unidentified carbohydrate
      kinase sequences. Five of the six newly identified sequences appear to be known
      types of carbohydrate kinases, four are glycerol kinases and one is a
      gluconokinase. The sixth newly identified sequence, the Caenorhabditis elegans
      gene, CER08D7.7-CEF59B2.1, shows similarity to the family of carbohydrate kinases
      including other glycerol kinases, xylulokinases, gluconokinases, ribulokinases,
      rhamnulokinases, and fucokinases. A phylogenetic comparison of this newly
      identified Caenorhabditis elegans gene with the other members of the carbohydrate
      kinase family demonstrated that this sequence cannot be assigned to one of the
      known classes of carbohydrate kinases.

PMID- 8521275
TI  - Improving the practical space and time efficiency of the shortest-paths approach
      to sum-of-pairs multiple sequence alignment.
AB  - The MSA program, written and distributed in 1989, is one of the few existing
      programs that attempts to find optimal alignments of multiple protein or DNA
      sequences. The MSA program implements a branch-and-bound technique together with
      a variant of Dijkstra's shortest paths algorithm to prune the basic dynamic
      programming graph. We have made substantial improvements in the time and space
      usage of MSA. The improvements make feasible a variety of problem instances that
      were not feasible previously. On some runs we achieve an order of magnitude
      reduction in space usage and a significant multiplicative factor speedup in
      running time. To explain how these improvements work, we give a much more
      detailed description of MSA than has been previously available. In practice, MSA
      rarely produces a provably optimal alignment and we explain why.

PMID- 8521276
TI  - Locating protein coding regions in human DNA using a decision tree algorithm.
AB  - Genes in eukaryotic DNA cover hundreds or thousands of base pairs, while the
      regions of those genes that code for proteins may occupy only a small percentage
      of the sequence. Identifying the coding regions is of vital importance in
      understanding these genes. Many recent research efforts have studied
      computational methods for distinguishing between coding and noncoding regions,
      and several promising results have been reported. We describe here a new
      approach, using a machine learning system that builds decision trees from the
      data. This approach combines several coding measures to produce classifiers with
      consistently higher accuracies than previous methods, on DNA sequences ranging
      from 54 to 162 base pairs in length. The algorithm is very efficient, and it can
      easily be adapted to different sequence lengths. Our conclusion is that decision
      trees are a highly effective tool for identifying protein coding regions.

PMID- 8521277
TI  - Substitution matrices and hidden Markov models.
AB  - Hidden Markov models (HMMs) provide a general framework for expressing primary
      sequence consensus. HMMs can effectively be used to model and align protein
      families, and to search data bases. HMMs, however, have a large number of
      parameters. When only few sequences are available for model fitting, additional
      prior information must be incorporated into the models. We derive a simple
      algorithm that directly incorporates prior information provided by substitution
      matrices into the HMM learning procedure.

PMID- 8521278
TI  - Analysis of the effects of modulatory agents on a modeled bursting neuron:
      dynamic interactions between voltage and calcium dependent systems.
AB  - In a computational model of the bursting neuron R15, we have implemented proposed
      mechanisms for the modulation of two ionic currents (IR and ISI) that play key
      roles in regulating its spontaneous electrical activity. The model was sufficient
      to simulate a wide range of endogenous activity in the presence of various
      concentrations of serotonin (5-HT) or dopamine (DA). The model was also
      sufficient to simulate the responses of the neuron to extrinsic current pulses
      and the ways in which those responses were altered by 5-HT or DA. The results
      suggest that the actions of modulatory agents and second messengers on this
      neuron, and presumably other neurons, cannot be understood on the basis of their
      direct effects alone. It is also necessary to take into account the indirect
      effects of these agents on other unmodulated ion channels. These indirect effects
      occur through the dynamic interactions of voltage-dependent and calcium-dependent
      processes.

PMID- 8521279
TI  - A multiscale dynamic routing circuit for forming size- and position-invariant
      object representations.
AB  - We describe a neural model for forming size- and position-invariant
      representations of visual objects. The model is based on a previously proposed
      dynamic routing circuit that remaps selected portions of an input array into an
      object-centered reference frame. Here, we show how a multiscale representation
      may be incorporated at the input stage of the model, and we describe the control
      architecture and dynamics for a hierarchical, multistage routing circuit.
      Specific neurobiological substrates and mechanisms for the model are proposed,
      and a number of testable predictions are described.

PMID- 8521280
TI  - Mechanisms of dendritic integration underlying gain control in fly motion
      sensitive interneurons.
AB  - In the compensatory optomotor response of the fly the interesting phenomenon of
      gain control has been observed by Reichardt and colleagues (Reichardt et al.,
      1983): The amplitude of the response tends to saturate with increasing stimulus
      size, but different saturation plateaus are assumed with different velocities at
      which the stimulus is moving. This characteristic can already be found in the
      motion-sensitive large field neurons of the fly optic lobes that play a role in
      mediating this behavioral response (Hausen, 1982; Reichardt et al., 1983;
      Egelhaaf, 1985; Haag et al., 1992). To account for gain control a model was
      proposed involving shunting inhibition of these cells by another cell, the so
      called pool cell (Reichardt et al., 1983), both cells sharing common input from
      an array of local motion detectors. This article describes an alternative model
      which only requires dendritic integration of the output signals of two types of
      local motion detectors with opposite polarity. The explanation of gain control
      relies on recent findings that these input elements are not perfectly
      directionally selective and that their direction selectivity is a function of
      pattern velocity. As a consequence, the resulting postsynaptic potential in the
      dendrite of the integrating cell saturates with increasing pattern size at a
      level between the excitatory and inhibitory reversal potentials. The exact value
      of saturation is then set by the activation ratio of excitatory and inhibitory
      input elements which in turn is a function of other stimulus parameters such as
      pattern velocity. Thus, the apparently complex phenomenon of gain control can be
      simply explained by the biophysics of dendritic integration in conjunction with
      the properties of the motion-sensitive input elements.

PMID- 8521281
TI  - Do neurons have a voltage or a current threshold for action potential initiation?
AB  - The majority of neural network models consider the output of single neurons to be
      a continuous, positive, and saturating firing rate f (t), while a minority treat
      neuronal output as a series of delta pulses sigma delta (t-ti). We here argue
      that the issue of the proper output representation relates to the biophysics of
      the cells in question and, in particular, to whether initiation of somatic action
      potentials occurs when a certain threshold voltage or a threshold current is
      exceeded. We approach this issue using numerical simulations of the electrical
      behavior of a layer 5 pyramidal cell from cat visual cortex. The dendritic tree
      is passive while the cell body includes eight voltage- and calcium-dependent
      membrane conductances. We compute both the steady-state (Istatic(infinity)(Vm))
      and the instantaneous (I0(Vm)) I-V relationships and argue that the amplitude of
      the local maximum in Istatic(infinity)(Vm) corresponds to the current threshold
      Ith for sustained inputs, while the location of the middle zero-crossing of I0
      corresponds to a fixed voltage threshold Vth for rapid inputs. We confirm this
      using numerical simulations: for "rapid" synaptic inputs, spikes are initiated if
      the somatic potential exceeds Vth, while for slowly varying input Ith must be
      exceeded. Due to the presence of the large dendritic tree, no charge threshold
      Qth exists for physiological input. Introducing the temporal average of the
      somatic membrane potential <Vm> while the cell is spiking repetitively, allows us
      to define a dynamic I-V relationship Idynamic(infinity)(<Vm>). We find an
      exponential relationship between <Vm> and the net current sunk by the somatic
      membrane during spiking (diode-like behavior). The slope of
      Idynamic(infinity)(<Vm>) allows us to define a dynamic input conductance and a
      time constant that characterizes how rapidly the cell changes its output firing
      frequency in response to a change in its input.

PMID- 8521283
TI  - The electric image in weakly electric fish: I. A data-based model of waveform
      generation in Gymnotus carapo.
AB  - Understanding how electrosensory images are generated and perceived in actively
      electrolocating fish requires the study of the characteristics of fish bodies as
      electric sources. This paper presents a model of Gymnotus carapo based on
      measurements of the electromotive force generated by the electric organ and the
      impedance of the passive tissues. A good agreement between simulated and
      experimentally recorded transcutaneous currents was obtained. Passive structures
      participate in the transformation of the electromotive force pattern into
      transcutaneous current profiles. These spatial filtering properties of the fish's
      body were investigated using the model. The shape of the transcutaneous current
      profiles depends on tissue resistance and on the geometry and size of the fish.
      Skin impedance was mainly resistive. The effect of skin resistance on the spatial
      filtering properties of the fish's body was theoretically analyzed. The model
      results show that generators in the abdominal and central regions produce most of
      the currents through the head. This suggests that the electric organ discharge
      (EOD), generated in the abdominal and central regions is critical for active
      electrolocation. In addition, the well-synchronized EOD components generated all
      along the fish produce large potentials in the far field. These components are
      probably involved in long-distance electrocommunication. Preliminary results of
      this work were published as a symposium abstract.

PMID- 8521282
TI  - Electrical consequences of spine dimensions in a model of a cortical spiny
      stellate cell completely reconstructed from serial thin sections.
AB  - We built a passive compartmental model of a cortical spiny stellate cell from the
      barrel cortex of the mouse that had been reconstructed in its entirety from
      electron microscopic analysis of serial thin sections (White and Rock, 1980).
      Morphological data included dimensions of soma and all five dendrites, neck
      lengths and head diameters of all 380 spines (a uniform neck diameter of 0.1
      micron was assumed), locations of all symmetrical and asymmetrical (axo-spinous)
      synapses, and locations of all 43 thalamocortical (TC) synapses (as identified
      from the consequences of a prior thalamic lesion). In the model, unitary
      excitatory synaptic inputs had a peak conductance change of 0.5 nS at 0.2 msec;
      conclusions were robust over a wide range of assumed passive-membrane parameters.
      When recorded at the soma, all unitary EPSPs, which were initiated at the spine
      heads, were relatively iso-efficient; each produced about 1 mV somatic
      depolarization regardless of spine location or geometry. However, in the spine
      heads there was a twentyfold variation in EPSP amplitudes, largely reflecting the
      variation in spine neck lengths. Synchronous activation of the TC synapses
      produced a somatic depolarization probably sufficient to fire the neuron;
      doubling or halving the TC spine neck diameters had only minimal effect on the
      amplitude of the composite TC-EPSP. As have others, we also conclude that from a
      somato-centric viewpoint, changes in spine geometry would have relatively little
      direct influence on amplitudes of EPSPs recorded at the soma, especially for a
      distributed, synchronously activated input such as the TC pathway. However,
      consideration of the detailed morphology of an entire neuron indicates that, from
      a dendro-centric point of view, changes in spine dimension can have a very
      significant electrical impact on local processing near the sites of input.

PMID- 8521284
TI  - Temporal encoding in nervous systems: a rigorous definition.
AB  - We propose a rigorous definition for the term temporal encoding as it is applied
      to schemes for the representation of information within patterns of neuronal
      action potentials, and distinguish temporal encoding schemes from those based on
      window-averaged mean rate encoding. The definition relies on the identification
      of an encoding time window, defined as the duration of a neuron's spike train
      assumed to correspond to a single symbol in the neural code. The duration of the
      encoding time window is dictated by the time scale of the information being
      encoded. We distinguish between the concepts of the encoding time window and the
      integration time window, the latter of which is defined as the duration of a
      stimulus signal that affects the response of the neuron. We note that the
      duration of the encoding and integration windows might be significantly
      different. We also present objective, experimentally assessable criteria for
      identifying neurons and neuronal ensembles that utilize temporal encoding to any
      significant extent. The definitions and criteria are made rigorous within the
      contexts of several commonly used analytical approaches, including the stimulus
      reconstruction analysis technique. Several examples are presented to illustrate
      the distinctions between and relative capabilities of rate encoding and temporal
      encoding schemes. We also distinguish our usage of temporal encoding from the
      term temporal coding, which is commonly used in reference to the representation
      of information about the timing of events by rate encoding schemes.

PMID- 8521285
TI  - Dynamic modification of dendritic cable properties and synaptic transmission by
      voltage-gated potassium channels.
AB  - Computer simulations of a dendrite possessing voltage-sensitive potassium
      conductances were used to determine the effects of these conductances on synaptic
      transmission and on the propagation of synaptic signals within the dendritic
      tree. Potassium conductances had two principal effects on voltage transients
      generated by current injections or synaptic conductances. Locally (near the
      source of the transient), voltage-gated potassium channels produced a potassium
      shunt current that reduced the amplitude of voltage transient increased and so
      acted to prevent large synaptic transients from reaching levels that would
      saturate due to a reduction in driving force. In the presence of rapidly
      activating potassium currents, excitatory synapses produced larger synaptic
      currents that were more linearly related to synaptic conductance, but these
      produced smaller voltage transients. The maximum amplitudes of the voltage
      transients were limited by the voltage sensitivity of the K+ conductance and the
      rate at which it could activate. Sufficiently rapid synaptic currents could
      outrun the K+ conductance and thus achieve high local peak amplitudes. These
      effects of K+ conductances were unrelated to whether they were located on
      dendrites or not, being related only to their proximity to the source of synaptic
      current. The second class of effects of K+ conductances depended on their
      alteration of the electronic structure of the postsynaptic cell and so were
      observed only when they were located on postsynaptic dendrites. Voltage-gated K+
      conductances produced voltage-dependent electronic expansion of depolarized
      dendrites, which had the effect of isolating synaptic inputs on depolarized
      dendrites from events on the rest of the neuron. Thus, synapses on the same
      dendrite interacted destructively to a degree much greater than that expected
      from the classical driving force nonlinearity. Synapses located proximally to a
      depolarized dendritic region were less effected than those located distally, and
      the range of the nonlinear interaction between synapses was dependent on the
      kinetics of activation and deactivation of the conductance. When present in
      conjunction with rapidly activating dendritic sodium conductance, the potassium
      conductance sharpened the requirement for spatial and temporal coincidence to
      produce synaptic boosting by inward currents, and suppressed out-of-synchrony
      synaptic inputs.

PMID- 8521286
TI  - Information flow and temporal coding in primate pattern vision.
AB  - We perform time-resolved calculations of the information transmitted about visual
      patterns by neurons in primary visual and inferior temporal cortices. All
      measurable information is carried in an effective time-varying firing rate,
      obtained by averaging the neuronal response with a resolution no finer than about
      25 ms in primary visual cortex and around twice that in inferior temporal cortex.
      We found no better way for a neuron receiving these messages to decode them than
      simply to count spikes for this long. Most of the information tends to be
      concentrated in one or, more often, two brief packets, one at the very beginning
      of the response and the other typically 100 ms later. The first packet is the
      most informative part of the message, but the second one generally contains new
      information. A small but significant part of the total information in the message
      accumulates gradually over the entire course of the response. These findings
      impose strong constraints on the codes used by these neurons.

PMID- 8521288
TI  - Modeling the leech heartbeat elemental oscillator. I. Interactions of intrinsic
      and synaptic currents.
AB  - We have developed a biophysical model of a pair of reciprocally inhibitory
      interneurons comprising an elemental heartbeat oscillator of the leech. We
      incorporate various intrinsic and synaptic ionic currents based on voltage-clamp
      data. Synaptic transmission between the interneurons consists of both a graded
      and a spike-mediated component. By using maximal conductances as parameters, we
      have constructed a canonical model whose activity appears close to the real
      neurons. Oscillations in the model arise from interactions between synaptic and
      intrinsic currents. The inhibitory synaptic currents hyperpolarize the cell,
      resulting in activation of a hyperpolarization-activated inward current Ih and
      the removal of inactivation from regenerative inward currents. These inward
      currents depolarize the cell to produce spiking and inhibit the opposite cell.
      Spike-mediated IPSPs in the inhibited neuron cause inactivation of low-threshold
      Ca++ currents that are responsible for generating the graded synaptic inhibition
      in the opposite cell. Thus, although the model cells can potentially generate
      large graded IPSPs, synaptic inhibition during canonical oscillations is
      dominated by the spike-mediated component.

PMID- 8521287
TI  - Interactions of glutamate and dopamine in a computational model of the striatum.
AB  - A network model of simplified striatal principal neurons with mutual inhibition
      was used to investigate possible interactions between cortical glutamatergic and
      nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic
      inputs were represented by an excitatory synaptic conductance and a slow membrane
      potassium conductance, respectively. Neuronal activity in the model was
      characterized by episodes of increased action potential firing rates of variable
      duration and frequency. Autocorrelation histograms constructed from the action
      potential activity of striatal model neurons showed that reducing peak excitatory
      conductance had the effect of increasing interspike intervals. On the other hand,
      the maximum value of the dopamine-sensitive potassium conductance was inversely
      related to the duration of firing episodes and the maximal firing rates. A
      smaller potassium conductance restored normal firing rates in the most active
      neurons at the expense of a larger proportion of neurons showing reduced
      activity. Thus, a homogeneous network with mutual inhibition can produce equally
      complex dynamics as have been proposed to occur in a striatal network with two
      neuron populations that are oppositely regulated by dopamine. Even without mutual
      inhibition it appears that increased dopamine concentrations could partially
      compensate for the effects of reduced glutamatergic input in individual neurons.

PMID- 8521289
TI  - Modeling the leech heartbeat elemental oscillator. II. Exploring the parameter
      space.
AB  - In the previous paper, we described a model of the elemental heartbeat oscillator
      in the leech. Here, the parameters of our model are explored around the baseline
      canonical model. The maximal conductances of the currents and the reversal
      potential of the leak current are varied to reveal the effects of individual
      currents and the interaction between synaptic and intrinsic currents in the
      model. The model produces two distinct modes of oscillation as the parameters are
      varied, S-mode and G-mode. These two modes are defined, their origin is
      identified, and the parameter space is mapped into S-mode and G-mode oscillation
      and no oscillation. Finally, we will make predictions for how the period can be
      modulated in heart interneurons.

PMID- 8521290
TI  - Quantitative estimate of the information relayed by the Schaffer collaterals.
AB  - Within the theory that describes the hippocampus as a device for the on-line
      storage of complex memories, the crucial autoassociative operations are ascribed
      mainly to the recurrent CA3 network. The CA3-to-CA1 connections may still be
      important, both in completing information retrieval and in re-expanding, with
      minimal information loss, the highly compressed representation retrieved in CA3.
      To quantify these effects, I have defined a suitably realistic formal model of
      the relevant circuitry, and evaluated its performance in the sense of information
      theory. Analytical estimates, calculated with mean-field, replica and saddle
      point techniques, of the amount of information present in the model CA1 output,
      reveal how such performance depends on different parameters characterising these
      connections. In particular, nearly all the stored information can be preserved if
      the model Schaffer collaterals are endowed with an optimal degree of Hebbian
      plasticity, matching that of the CA3 recurrent collaterals.

PMID- 8521291
TI  - Transforming biology.

PMID- 8521292
TI  - Studies on the chemical nature of the substance inducing transformation of
      pneumococcal types. Induction of transformation by a desoxyribonucleic acid
      fraction isolated from Pneumococcus type III. 1944.

PMID- 8521293
TI  - The Institute of Molecular Medicine, University of Oxford.

PMID- 8521294
TI  - The MD PhD physician scientist--endangered species or the next generation?

PMID- 8521295
TI  - Normal and expanded Huntington's disease gene alleles produce distinguishable
      proteins due to translation across the CAG repeat.
AB  - BACKGROUND: An expanded CAG trinucleotide repeat is the genetic trigger of
      neuronal degeneration in Huntington's disease (HD), but its mode of action has
      yet to be discovered. The sequence of the HD gene places the CAG repeat near the
      5' end in a region where it may be translated as a variable polyglutamine segment
      in the protein product, huntingtin. MATERIALS AND METHODS: Antisera directed at
      amino acid stretches predicted by the DNA sequence upstream and downstream of the
      CAG repeat were used in Western blot and immunohistochemical analyses to examine
      huntingtin expression from the normal and the HD allele in lymphoblastoid cells
      and postmortem brain tissue. RESULTS: CAG repeat segments of both normal and
      expanded HD alleles are indeed translated, as part of a discrete approximately
      350-kD protein that is found primarily in the cytosol. The difference in the
      length of the N-terminal polyglutamine segment is sufficient to distinguish
      normal and HD huntingtin in a Western blot assay. CONCLUSIONS: The HD mutation
      does not eliminate expression of the HD gene but instead produces an altered
      protein with an expanded polyglutamine stretch near the N terminus. Thus, HD
      pathogenesis is probably triggered by an effect at the level of huntingtin
      protein.

PMID- 8521296
TI  - Thalidomide treatment reduces tumor necrosis factor alpha production and enhances
      weight gain in patients with pulmonary tuberculosis.
AB  - BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha (TNF
      alpha), is essential for host immunity, but overproduction of this cytokine may
      have serious pathologic consequences. Excess TNF alpha produced in pulmonary
      tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive
      weight loss. Thalidomide (alpha-N-phthalimidoglutarimide) has recently been shown
      to suppress TNF alpha production by human monocytes in vitro and to reduce serum
      TNF alpha in leprosy patients. We have therefore conducted a two-part placebo
      controlled pilot study of thalidomide in patients with active tuberculosis to
      determine its effects on clinical response, immune reactivity, TNF alpha levels,
      and weight. MATERIALS AND METHODS: 30 male patients with active tuberculosis,
      either human immunodeficiency virus type 1 positive (HIV-1+) or HIV-1-, received
      thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the
      study drug, delayed type hypersensitivity (DTH), cytokine production, and weight
      gain were evaluated. RESULTS: Thalidomide treatment was well tolerated, without
      serious adverse events. The drug did not adversely affect the DTH response to
      purified protein derivative (PPD), total leukocyte, or differential cell counts.
      TNF alpha production was significantly reduced during thalidomide treatment while
      interferon-gamma (IFN gamma) production was enhanced. Daily administration of
      thalidomide resulted in a significant enhancement of weight gain. CONCLUSIONS:
      The results indicate that thalidomide is well tolerated by patients receiving
      anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production
      both in vivo and in vitro and is associated with an accelerated weight gain
      during the study period.

PMID- 8521297
TI  - Clozapine: selective labeling of sites resembling 5HT6 serotonin receptors may
      reflect psychoactive profile.
AB  - BACKGROUND: Clozapine, the classic atypical neuroleptic, exerts therapeutic
      actions in schizophrenic patients unresponsive to most neuroleptics. Clozapine
      interacts with numerous neurotransmitter receptors, and selective actions at
      novel subtypes of dopamine and serotonin receptors have been proposed to explain
      clozapine's unique psychotropic effects. To identify sites with which clozapine
      preferentially interacts in a therapeutic setting, we have characterized
      clozapine binding to brain membranes. MATERIALS AND METHODS: [3H]Clozapine
      binding was examined in rat brain membranes as well as cloned-expressed 5-HT6
      serotonin receptors. RESULTS: [3H]Clozapine binds with low nanomolar affinity to
      two distinct sites. One reflects muscarinic receptors consistent with the drug's
      anticholinergic actions. The drug competition profile of the second site most
      closely resembles 5HT6 serotonin receptors, though serotonin itself displays low
      affinity. [3H]Clozapine binding levels are similar in all brain regions examined
      with no concentration in the corpus striatum. CONCLUSIONS: Besides muscarinic
      receptors, clozapine primarily labels sites with properties resembling 5HT6
      serotonin receptors. If this is also the site with which clozapine principally
      interacts in intact human brain, it may account for the unique beneficial actions
      of clozapine and other atypical neuroleptics, and provide a molecular target for
      developing new, safer, and more effective agents.

PMID- 8521298
TI  - Antiviral drugs from the nucleoside analog family block volume-activated chloride
      channels.
AB  - BACKGROUND: The antiviral drugs AZT and acyclovir are generally used in the
      treatment of infections with human immunodeficiency virus (HIV) and herpes
      simplex virus (HSV). These substances are known to impede virus replication by
      premature nucleic acid chain termination. It is not yet clear, however, if this
      is the sole mechanism responsible for the antiviral and/or the numerous side
      effects observed in patients treated with these agents. We investigated the
      swelling-induced chloride current in fibroblasts, which we demonstrated is
      closely related or identical to a cloned epithelial chloride channel, ICln: This
      chloride channel can be blocked by nucleotides. MATERIALS AND METHODS:
      Electrophysiological, fluorescence optical, and volume measurements were made to
      determine the effect of nucleoside analogs on the swelling-dependent chloride
      current (ICl) in NIH 3T3 fibroblasts and in human T cell lymphoma (H9) cells and
      the cAMP-dependent chloride current in CaCo cells. RESULTS: AZT and acyclovir
      block the swelling-dependent chloride current and the chloride flux in
      fibroblasts, and the regulatory volume decrease (RVD) and ICl in H9 cells. This
      immediate effect can be substantially reduced by the simultaneous incubation of
      the cells with thymidine-5'-diphosphate (TDP) or uridine, both of which are by
      themselves unable to affect ICl. CONCLUSIONS: We show here a novel molecular
      mechanism by which antiviral drugs of the nucleoside analog family could lead to
      impairments of the kidney, bone marrow, gastrointestinal, and neuronal functions,
      and how these side effects could possibly be restricted by the presence of TDP or
      uridine.

PMID- 8521299
TI  - The tissue inhibitor of metalloproteinases-3 gene in breast carcinoma:
      identification of multiple polyadenylation sites and a stromal pattern of
      expression.
AB  - BACKGROUND: Tissue inhibitor of metalloproteinases-3 (TIMP3) is the third member
      of the TIMP family of proteins, believed to play a significant role in
      controlling extracellular matrix remodeling. MATERIALS AND METHODS: Differential
      screening of a human breast carcinoma cDNA library using substracted and PCR
      amplified cDNA probes identified a 4.6-kb TIMP3 cDNA, which was used for further
      cDNA library screenings, Northern blot hybridizations, and the synthesis of
      riboprobes for in situ RNA hybridization analyses. RESULTS: The 4.6-kb full
      length TIMP3 cDNA contains 3.7 kb of 3'-untranslated sequence. Additional TIMP3
      cDNAs subsequently identified were colinear with the original sequence, but
      revealed use of four different polyadenylation signals within the 3'-untranslated
      region, which accounted for the 4.6-, 2.7-, 2.5-, and 2.1-kb TIMP3 transcripts
      noted in this and in previous studies. In situ RNA hybridizations demonstrated
      that in breast carcinoma the TIMP3 gene was predominantly expressed by
      fibroblastic cells within the tumor stroma adjacent to cancer cells. TIMP3
      transcripts were also strongly detected in fibroblastic decidual cells of
      pregnant endometrium. CONCLUSIONS: Modulating the length of the 3'-untranslated
      region may represent a mechanism by which TIMP3 gene expression is controlled in
      tissues. The strong expression of the TIMP3 gene by fibroblastic cells in breast
      carcinoma supports the importance of tumor stroma as a source of factors
      influencing human carcinoma growth and progression.

PMID- 8521300
TI  - LPS and Taxol activate Lyn kinase autophosphorylation in Lps(n), but not in
      Lpsd), macrophages.
AB  - BACKGROUND: The anti-tumor agent, Taxol, has been shown in murine macrophages to
      stimulate tumor necrosis factor (TNF), modulate TNF receptors, induce a large
      panel of immediate-early genes, and induce protein tyrosine phosphorylation
      indistinguishably from LPS. These data, coupled with the finding that lipid A
      antagonists block Taxol-induced stimulation, support the hypothesis that these
      two structurally unrelated compounds activate a common, receptor-associated
      signaling apparatus. A very early event in LPS signaling of human monocytes is
      activation of lyn kinase activity. We therefore sought to evaluate the activation
      of lyn kinase by LPS and Taxol in LPS-responsive (Lps(n)) and LPS-hyporesponsive
      (Lps(d)) macrophages. MATERIALS AND METHODS: C3H/OuJ (Lps(n)) and C3H/HeJ
      (Lps(d)) macrophages were stimulated by LPS or Taxol. Cell lysates were subjected
      to immunoprecipitation with anti-lyn antibody, gel electrophoresis, and in vitro
      kinase assays. Autoradiography and Phosphor-Imager analysis were carried out to
      detect incorporation of 32P into lyn protein. RESULTS: Within seconds of
      stimulation, LPS and Taxol induce in Lps(n) macrophages a depression of
      autophosphorylation, followed within minutes by autophosphorylation of both p53
      and p56 lyn species. Lps(d) macrophages respond to LPS and Taxol with the initial
      decrease in activity, but fail to respond to LPS with autophosphorylation, and
      respond only to a limited extent upon Taxol stimulation. Tyrosine phosphatase
      inhibitors exerted inhibitory effects on LPS stimulation of lyn
      autophosphorylation. CONCLUSIONS: Decreased lyn kinase activity within seconds
      and autophosphorylation within minutes of LPS or Taxol stimulation in Lps(n)
      macrophages strongly supports the hypothesis that LPS and Taxol share a common
      signaling pathway. The finding that C3H/HeJ macrophages respond to LPS and Taxol
      with a normal depression of lyn activity, but fail to autophosphorylate lyn
      normally in response to LPS or Taxol, suggests that the Lps(d) defect is distal
      to LPS-receptor interaction. Finally, the inhibitory effect of tyrosine
      phosphatase inhibitors on LPS-induced lyn autophosphorylation suggests that
      tyrosine phosphatase(s) may participate in the regulation of lyn kinase activity.

PMID- 8521301
TI  - The MarR repressor of the multiple antibiotic resistance (mar) operon in
      Escherichia coli: prototypic member of a family of bacterial regulatory proteins
      involved in sensing phenolic compounds.
AB  - BACKGROUND: The marR gene of Escherichia coli encodes a repressor of the marRAB
      operon, a regulatory locus controlling multiple antibiotic resistance in this
      organism. Inactivation of marR results in increased expression of marA, which
      acts at several target genes in the cell leading to reduced antibiotic
      accumulation. Exposure of E. coli to sodium salicylate (SAL) induces marRAB
      operon transcription and antibiotic resistance. The mechanism by which SAL
      antagonizes MarR repressor activity is unclear. MATERIALS AND METHODS:
      Recombinant plasmid libraries were introduced into a reporter strain designed to
      identify cloned genes encoding MarR repressor activity. Computer analysis of
      sequence databases was also used to search for proteins related to MarR. RESULTS:
      A second E. coli gene, MprA, that exhibits MarR repressor activity was
      identified. Subsequent database searching revealed a family of 10 proteins from a
      variety of bacteria that share significant amino acid sequence similarity to MarR
      and MprA. At least four of these proteins are transcriptional repressors whose
      activity is antagonized by SAL or by phenolic agents structurally related to SAL.
      CONCLUSIONS: The MarR family is identified as a group of regulatory factors whose
      activity is modulated in response to environmental signals in the form of
      phenolic compounds. Many of these agents are plant derived. Some of the MarR
      homologs appear more likely to control systems expressed in animal hosts,
      suggesting that phenolic sensing by bacteria is important in a variety of
      environments and in the regulation of numerous processes.

PMID- 8521302
TI  - Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1)
      expression and atheroma formation in normal rabbits.
AB  - BACKGROUND: Reactive glucose-protein intermediates and advanced glycation
      endproducts (AGEs) are shown to colocalize with atheromatous lesions and to
      trigger complex chemical and biological responses through interaction with vessel
      wall elements. In diabetes and renal insufficiency, atherosclerosis is common, as
      are elevated levels of serum and vascular tissue AGEs. In the present study, AGEs
      supplied exogenously to normal animals elicited vascular and renal pathology.
      MATERIALS AND METHODS: Nondiabetic rabbits were injected intravenously with low
      doses of AGE-modified rabbit serum albumin (AGE-RSA, 16 mg/kg/day) for 4 months
      alone, or combined with a brief terminal period (2 weeks) of a cholesterol-rich
      diet (CRD) (2% cholesterol, 10% corn oil). AGE-RSA associated expression of
      vascular cell adhesion molecules and the development of atheromatous changes
      within the aorta were determined by immunohistology. RESULTS: The AGE content of
      aortic tissue increased by 2.2-fold in AGE-treated and by 3.2-fold in AGE + CRD
      treated rabbits compared with normal saline-treated control rabbits (p < 0.025
      and 0.001, respectively). Serum AGE levels in AGE groups rose up to 3-fold above
      the controls (p < 0.025 and p < 0.01). Ascending aortic sections from AGE-treated
      rabbits showed significant focal intimal proliferation, enhanced endothelial cell
      adhesion with infrequent intimal macrophages. oil-red-O staining lipid deposits
      and positive focal expression of vascular cell adhesion molecule-1 (VCAM-1), and
      intercellular adhesion molecule-1 (ICAM-1), a pattern not observed in controls.
      These AGE-induced changes were markedly enhanced in animals cotreated with AGEs
      and a brief period of CRD. Lesions consisted of multifocal atheromas, containing
      foam cells, massive lipid droplets, and strong endothelial expression of VCAM-1
      and ICAM-1 restricted to the affected areas. CONCLUSIONS: This study provides in
      vivo evidence for a causal relationship between chronic AGE accumulation and
      atherosclerosis independent of diabetic hyperglycemia, and suggests the utility
      of this animal model for the study of diabetic vascular disease in relation to
      glycation.

PMID- 8521304
TI  - Molecular medicine database.

PMID- 8521303
TI  - Expression of the Von Hippel-Lindau tumor suppressor gene, VHL, in human fetal
      kidney and during mouse embryogenesis.
AB  - BACKGROUND: Von Hippel-Lindau (VHL) disease is a familial cancer syndrome that
      has a dominant inherited pattern which predisposes affected individuals to a
      variety of tumours. The most frequent tumors are hemangioblastomas of the central
      nervous system and retina, renal cell carcinoma (RCC), and pheochromocytoma. The
      recent identification and characterization of the VHL gene on human chromosome 3p
      and mutational analyses confirms the VHL gene functions as a classical tumor
      suppressor. Not only are mutations in this gene responsible for the VHL syndrome,
      but mutations are also very frequent in sporadic RCC. MATERIALS AND METHODS: VHL
      expression in human kidney and during embryogenesis, was analyzed by in situ mRNA
      hybridization with 35S-labeled antisense VHL probes, derived from human and mouse
      cDNAs, on cryosections of human fetal kidney and paraffin sections of murine
      embryos. RESULTS: In human fetal kidney, there was enhanced expression of VHL
      within the epithelial lining of the proximal tubules. During embryogenesis, VHL
      expression was ubiquitous in all three germ cell layers and their derivatives.
      Expression occurred in the cerebral cortex, midbrain, cerebellum, retina, spinal
      cord, and postganglionic cell bodies. All organs of the thoracic and abdominal
      cavities expressed VHL, but enhanced expression was most apparent in the
      epithelial components of the lung, kidney, and eye. CONCLUSIONS: In human fetal
      kidney, the enhanced epithelial expression of the VHL gene is consistent with the
      role of this gene in RCC. There is widespread expression of the VHL gene during
      embryogenesis, but this is pronounced in areas associated with VHL phenotypes.
      These findings provide a histological framework for investigating the
      physiological role of the VHL gene and as basis for further mutational analysis.

PMID- 8521305
TI  - Paediatric cardiopulmonary resuscitation.

PMID- 8521306
TI  - Oral transmucosal fentanyl citrate for preanaesthetic medication of paediatric
      cardiac surgery patients.
AB  - The safety and efficacy of oral transmucosal fentanyl citrate (OTFC) as a
      preanaesthetic medication were evaluated in 42 children aged two to twelve years
      scheduled to undergo general anaesthesia for open cardiac surgery. Patients were
      randomly assigned to receive either a placebo lozenge or a lozenge of 15-20
      micrograms.kg-1) OTFC 45 min preoperatively and were managed in a double-blinded
      manner. Heart rate, respiratory rate (RR), blood pressure, and digital pulse
      oximetry (SpO2) were monitored throughout the study. Scoring systems were
      utilized to evaluate sedation, anxiety, cooperation, and ease and quality of
      parental separation and anaesthetic induction. Adverse effects were noted.
      Preoperatively, sedation was observed in both groups, but children receiving OTFC
      had significantly less distress at time of separation from parents. Clinically
      significant less distress at and SpO2 were observed more frequently in children
      in the OTFC group than in the placebo group. The authors conclude that, in
      paediatric cardiac surgical patients, OTFC induces preoperative sedation and
      facilitates separation of the patients from their parents, but is associated with
      decreases in respiratory rate and SpO2 that may be of clinical importance.

PMID- 8521307
TI  - Complications in regional anaesthesia.

PMID- 8521308
TI  - Comparison of the flow rates of central venous catheters designed for rapid
      transfusion in infants and small children.
AB  - Large-bore Hickman catheters are useful in infants and small children for the
      rapid transfusion of blood or fluids into the central circulation. Recently high
      flow plastic sheaths have been developed for the same purpose. We compared the
      flow rates of normal saline, 5% albumin and packed red blood cells through two
      sizes of Hickman catheters that have been recommended for major surgery in
      infants to five sizes of Arrow plastic sheaths of comparable external diameters,
      and to 14 and 16 gauge Jelco catheters. The flow rates of all three solutions
      through the plastic sheaths and the 14 gauge Jelco catheters were superior to
      both sizes of Hickman catheters. Shortening the Hickman catheters improved their
      flow. High-flow plastic sheaths can provide a useful alternative to Hickman
      catheters in patients where permanent, large-bore central venous catheters are
      not required. Hickman catheters should be shortened as much as safely possible if
      massive haemorrhage is anticipated.

PMID- 8521309
TI  - Accidents following extradural analgesia in children. The results of a
      retrospective study.
AB  - A retrospective multicentre study of the complications observed after regional
      anaesthesia in children was undertaken in 1991 at the request of the association
      of Anesthesistes-Reanimateurs Pediatriques d'Expression Francaise (ADARPEF). The
      incidence of accidents seen in the study was comparable to that found in the
      literature. Five cases which were exceptional due to the severity of the sequelae
      have been analysed separately. Different pathophysiological mechanisms are
      proposed.

PMID- 8521310
TI  - Dose of propofol required to insert the laryngeal mask airway in children.
AB  - We have assessed the ease of insertion of the Brain Laryngeal Mask Airway (LMA)
      after induction of anaesthesia with propofol in 60 healthy unpremedicated
      children aged between four and nine years. Patients were randomly allocated into
      three groups: group A = propofol 2.5 mg.kg-1; group B = propofol 3 mg.kg-1 and
      group C = propofol 3.5 mg.kg-1. Propofol was mixed with lignocaine 0.5 mg.kg-1.
      Insertion conditions were assessed subjectively as good, acceptable, unacceptable
      or impossible. Insertion of the LMA was possible in all patients. Good and
      acceptable conditions were obtained in 35%, 70% and 95% in groups A, B, and C
      respectively (P < 0.0001). There was no statistically significant inter group
      variation in systolic and diastolic arterial pressure or in heart rate for five
      min after induction. All measured cardiovascular changes were considered to be
      clinically insignificant in healthy children. We conclude it is safe and
      effective to insert a LMA immediately after induction of anaesthesia with
      propofol 3.5 mg.kg-1.

PMID- 8521311
TI  - CRIES: a new neonatal postoperative pain measurement score. Initial testing of
      validity and reliability.
AB  - We have developed a neonatal pain assessment tool CRIES. The tool is a ten point
      scale similar to the APGAR score (Apgar 1953). It is an acronym of five
      physiological and behavioural variables previously shown to be associated with
      neonatal pain. C--Crying; R--Requires increased oxygen administration; I-
      Increased vital signs; E--Expression; S--Sleeplessness. We have tested CRIES for
      validity and reliability. This report is the result of that testing. We have
      found CRIES to be valid, reliable and well accepted by neonatal nurses.

PMID- 8521312
TI  - Transnasal butorphanol for postoperative analgesia following paediatric surgery
      in a Third World country.
AB  - The authors present their experience with transnasal butorphanol to provide
      analgesia following orthopaedic and plastic surgical procedures in children.
      Transnasal butorphanol was administered to eight patients ranging in age from
      eight to 17 years and in weight from 34 to 64 kg. Following the surgical
      procedure, the patient and a parent were instructed on how to use the medication.
      They were instructed to administer one spray into one nostril every three h as
      needed for pain. The quality of analgesia was assessed twice a day using a visual
      analogue score of 0 to 10 (0 = no pain, 10 = worst pain imaginable). Intranasal
      butorphanol provided adequate analgesia in all eight patients with visual
      analogue scores of zero to two. Adverse effects from the medication included one
      report of nausea, one complaint of transient dizziness, and two reports of a
      bitter taste and some mild throat irritation. None of these was severe enough to
      preclude its subsequent use. Our preliminary experience suggests that transnasal
      butorphanol may offer an alternative route of delivery when intravenous
      administration is not feasible. Future studies are needed to compare its efficacy
      to intravenous and non-parenteral routes of administration. It may prove to be
      useful in other situations when intravenous access is lacking such as prior to
      invasive procedures in the outpatient clinic or emergency room.

PMID- 8521313
TI  - Aortic aneurysm in a four-year-old child with tuberous sclerosis.
AB  - We present a case of aortic aneurysm in a four-year-old child complicated with
      tuberous sclerosis. We used the same general principles as for adult patients and
      successfully managed our patient. Our methods included the use of isoflurane plus
      epidural anaesthesia, dopamine to maintain blood pressure, and induced mild
      hypothermia to reduce brain metabolism and to prevent spinal cord damage during
      aortic cross-clamping. Intensive monitoring including EEG was beneficial to the
      anaesthetic management.

PMID- 8521314
TI  - Anaesthetic management of a 2.900 kg neonate with a C3-C4 dislocation.

PMID- 8521315
TI  - An evaluation of the laryngeal mask airway during routine paediatric anaesthesia.

PMID- 8521316
TI  - Whooping cough and anaesthesia.

PMID- 8521317
TI  - [Computerized tomography and pre-implant assessment].

PMID- 8521318
TI  - Toluidine blue.

PMID- 8521319
TI  - Oral and maxillofacial radiology: striving for adequacy?

PMID- 8521320
TI  - HIV discrimination case.

PMID- 8521321
TI  - Oral cancer.

PMID- 8521322
TI  - 100 years of radiology: those early years.

PMID- 8521323
TI  - Surface and internal absorbed doses in mandibular and maxillary occlusal
      radiography.
AB  - The objective of this study was to determine the absorbed radiation doses to
      various structures within the head and neck as a result of routine mandibular and
      maxillary occlusal radiography. Five projections were investigated: the anterior
      mandibular; true mandibular; anterior maxillary; lateral maxillary; and maxillary
      vertex occlusal radiographic views. Standard thermoluminescent dosimetry
      methodology was employed using a humanoid phantom of the skull. Multiple
      exposures were done for each view to ensure adequate precision. The absorbed
      doses to various locations following a single occlusal exposure are presented in
      centiGray (cGy). It was found that the absorbed dose values for occlusal
      radiography observed in this study were similar in magnitude to previously
      reported absorbed dose values for other forms of dental radiography. Values
      ranged from 0.0014 cGy to 1.301 cGy. The highest absorbed doses were generally
      the skin entrance doses. The results of this study provide an accurate, concise
      summary of surface and internal absorbed radiation doses for five commonly used
      occlusal radiographs. They can be used in the calculation of risk estimates for
      dental radiography, and may assist dentists in their discussions with patients
      concerned about radiation exposure.

PMID- 8521324
TI  - Digital dental imaging systems: a review.

PMID- 8521325
TI  - Educational use of indirect digital radiographic imaging.

PMID- 8521326
TI  - Radiographic selection protocol for new and recall patients in U.S. and Canadian
      dental schools.
AB  - This study indicates that a growing number of dental schools are now using
      individual selection criteria to determine which radiographs, if any, are
      required for screening new and recall patients. A majority of Canadian schools
      are in compliance with CDA's Guidelines For the Control Of Radiation In the
      Dental Office, which state that the frequency of radiological examination is a
      matter of clinical judgment, and that it should not be considered as a routine
      procedure. In general, most schools support the use of individual selection
      criteria prior to requesting radiographs. The results of this study also indicate
      that more U.S. dental schools now follow the U.S. Food and Drug Administration's
      (FDA) recommendations on radiation exposure than at any other time in history.
      However, both the FDA recommendations and the American Association of Dental
      Schools' guidelines for prescribing radiographs are only recommendations, which
      are subject to clinical judgment, and may not be applied universally to all
      patients.

PMID- 8521327
TI  - The changing face of HIV infection: charting the pattern of AIDS in Canada and
      the United States.

PMID- 8521328
TI  - Dental casualties during Canadian UN operations in Somalia.
AB  - The Canadian Forces Dental Services (CFDS) provides dental support to Canadian
      Forces (CF) on selected United Nations (UN) duties. This study investigated the
      nature of dental care sought by and provided to 1,000 Canadian regular force UN
      peacekeepers by CFDS from January to May 1993, during a 149 day UN mission to
      Somalia. Care was categorized as either emergency, urgency, or routine. Emergency
      and urgency care represented 10 per cent and 25 per cent of the 269 patient
      encounters, respectively. The dental casualty rate (per 1,000 tropps per year)
      was 232.

PMID- 8521329
TI  - Transcranial color-coded sonography in normal Chinese adults and its clinical
      applications.
AB  - We have performed transcranial color-coded sonography to 150 normal adults.
      Through the temporal, orbital and foraminal windows, by using a 2 MHz pulsed-wave
      transducer, we were able to directly insonate the brain parenchyma, and to obtain
      color-coded Doppler vascular imagings and flow velocities of the intracranial
      basal cerebral arteries. There was no significant difference of blood flow
      velocities and resistance index between the right and left hemispheres. The mean
      velocities was highest in the middle cerebral artery and lowest in the ophthalmic
      artery while which had the highest resistance index. Female had higher mean
      velocity in basilar artery. The mean velocity, peak systolic velocity, as well as
      end diastolic velocity decreased significantly with age in middle cerebral
      artery, anterior cerebral artery and basilar artery. Four illustrative cases with
      abnormal findings were presented to compare with normal control. Some pitfalls in
      ultrasonography were also described.

PMID- 8521330
TI  - Rebleeding rate of various stigmata of recent hemorrhage in peptic ulcer bleeding
      with different severity.
AB  - The stigmata of recent hemorrhage (SRH) have been used as a factor for predicting
      peptic ulcer rebleeding. In previous studies, the rebleeding rate of the visible
      vessel varied. A hypothesis had been proposed stating that the evolution of the
      color of the stigmata depends on the point in the healing process of the blood
      clot on the bleeding ulcer. This retrospective study evaluates the rebleeding
      rates associated with various colors of stigmata of recent hemorrhage. Of a total
      of 623 cases of peptic ulcer bleeding (474 male and 149 female, with a mean age
      of 59 years old), there were 232 gastric ulcers, 369 duodenal ulcers, and 22
      stomal ulcers. Stigmata of recent hemorrhage were found in 387 cases (62%). The
      overall rebleeding rate for those with gastric ulcers was higher than for those
      with duodenal ulcers (24.2% versus 16.3%, p<0.05), especially for oozing and
      sentinel clots, the rebleeding rates for active bleeding, blood clots, sentinel
      clots, and others were 35%, 24.8%, 17%, and 11.3% respectively. The red clot of
      stigmata of recent hemorrhage had a slightly higher rebleeding rate than the
      black clot, but the difference was not statistically important. Furthermore, the
      5 duodenal ulcers with white sentinel clots experienced no rebleeding. When
      comparing the rebleeding rates between groups with massive and minor bleeding, a
      significantly higher rebleeding rate was found in the massive bleeding group
      (50.5% versus 6.6%, p < 0.001). It can thus be seen that the different types of
      stigmata of recent hemorrhage represent different stages in the healing process
      of a bleeding ulcer. A white sentinel clot had a change of not
      rebleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521331
TI  - Portal vein velocity by duplex Doppler ultrasound as an indication of the
      clinical severity of portal hypertension.
AB  - The portal vein (PV) velocity was measured by duplex Doppler ultrasound to
      predict the severity of portal hypertension. A total of 143 patients with liver
      cirrhosis were studied from January 1991 to June 1992. There were 104 males and
      39 females with a mean age of 52 years old (range 23-76). The maximal PV velocity
      was significantly lower in patients with moderate and severe varices, cardiac
      varices, red-color signs on varix, esophagitis and congestive gastropathy. The
      patients with bleeding esophageal varices or upper gastrointestinal tract were
      found to have a significantly maximal PV velocity. Comparing patients without
      ascites or victims with controllable ascites. The maximal PV velocity in Child's
      C or mortality cases was also significantly lower than that in Child's A, Child's
      B and surviving cases. If we set the cut off value of PV velocity at 15 cm/sec,
      we could get the accuracy of 67.8%, 62.2%, 67.8% and 73.5% in the prediction of
      massive ascites, varices severity, Child C class and mortality respectively. In
      conclusion, PV velocity may reflect the severity of clinical portal hypertension
      in cirrhotic patients; it could be a prognostic factor in cirrhotic patients.

PMID- 8521332
TI  - Descriptive study of prognostic factors influencing survival of patients with
      primary tracheal tumors.
AB  - From 1977 to 1992, 23 patients with primary tumors of the trachea were reviewed.
      Nineteen of these patients had squamous cell carcinomas, 2 had adenoid cystic
      carcinomas, 1 had a small cell carcinoma, 1 had a poorly differentiated
      carcinoma, and 1 had a pleomorphic adenoma. The prognosis of squamous cell, small
      cell and poorly differentiated carcinomas appeared to be grave, especially in
      association with vocal cord palsy (26%). Short-term survival occurred in 7 to 9
      patients with tumors in the upper-middle third of trachea and 4 of them had
      concurrent acute respiratory distress. Cough (65.2%), dyspnea (91.3%), and
      hemoptysis (47.8%) were the most common symptoms. For patients with hoarseness,
      dysphagia, and cervical lymphadenopathy, the prognosis was poor (p < 0.0010). Two
      patients (8.7%) had multiple malignancies and all died within 1 year. Smoking was
      not only a risk factor as reported in previous studies, but also a significant
      prognostic factor (p = 0.0020) in our series. Emergent irradiation ( < 40 Gy in
      our cases) was useful in alleviating acute respiratory distress, but worthwhile
      survival was only obtained by the combination of surgery and radiation therapy (p
      = 0.0200, compared with surgery or irradiation, respectively). There was a
      significant correlation between prognosis and histologic type, tumor location,
      clinical presentation, smoking history and management, but not roentography or
      tumor size. These factors can be used to assess the survival of patients with
      primary tracheal tumors.

PMID- 8521334
TI  - Midtrimester human chorionic gonadotropin levels: normal reference values in
      Chinese pregnant women.
AB  - In order to establish normative median values of maternal serum total human
      chorionic gonadotropin (hCG) at our own laboratory, 2711 normal sera were
      collected from uncomplicated, singleton Chinese pregnant women, including 1705
      samples measured by radioimmunoassay (RIA) between 13 and 24 weeks' gestation and
      1006 samples measured by enzyme immunoassay (EIA) between 14 and 20 weeks'
      gestation. The hCG secretion pattern throughout midtrimester measured by RIA is
      similar to that of measured by both RIA and EIA have a steep drop initially and
      then steadily decline from 17 weeks of gestation. The total (hCG levels measured
      by RIA and EIA showed different normative median values and distribution. If it
      was measured by RIA between 14 and 20 week's gestation, there were 3.7% and 17.8%
      of pregnancies with serum total hCG levels less than 0.25 multiple of the median
      (MoM) and 0.5 MoM, retrospectively, and 11.6% and 5.5% among them with serum
      levels above 2.0 MoM and 2.5 MoM, respectively. When it was measured by EIA,
      there were 0.7% and 9.2% of pregnancies with serum total hCG levels less than
      0.25 MoM and 0.5 MoM, respectively, and 8.9% and 3.7% among them with serum
      levels above 2.0 MoM and 2.5 MoM, respectively. Accurate and satisfactory
      interpretation of maternal serum screening for Down syndrome depends on
      establishment of a well-developed normative median value for each week of
      gestation. Any laboratory intends to provide hCG for maternal serum screening
      should have its own reference data by its own immunoassay method.

PMID- 8521333
TI  - Clinical presentations and results of therapy of 63 acromegalic patients Chang
      Gung Memorial Hospital.
AB  - Retrospective analysis of 63 acromegalic patients who received regular follow-up
      in Chang Gung Memorial Hospital is presented. Our purpose was to examine clinical
      characteristics of acromegalic patients and the results of combination therapy in
      this medical center. Fifty-one cases received operative treatment. Among them, 43
      cases presented with extrasella involvement of the pituitary tumor. Postoperative
      external radiotherapy was performed in 20 cases. Thirteen cases received medical
      treatment with bromocriptine or octreotide. After surgery, growth hormone (GH)
      levels in 23 out of 51 cases (45.1%) were reduced to less than 5 ng/mL. In cases
      which received postoperative radiotherapy, mean GH level could be reduced
      gradually after the treatment. In the group treated with bromocriptine, the GH
      level was controlled in three of nine patients. In five of the six cases who
      received octreotide therapy. GH levels were maintained at less than 5 ng/mL.
      Although GH levels were reduced after octreotide treatment, the paradoxical
      response to the thyrotropin-releasing hormone (TRH) stimulation test still
      persisted. The data presented in this study suggest that after combination
      therapy for acromegalic patients (most cases with pituitary macroadenoma), the
      serum GH levels in 90% cases could be maintained at less than 5 ng/mL.

PMID- 8521335
TI  - Human recombinant erythropoietin and phlebotomy in the treatment of iron overload
      in uremic patients.
AB  - Six chronic hemodialysis patients suffering from iron overload (serum ferritin
      ranged between 2053-15704 mu g/L) were treated with human recombinant
      erythropoietin (EPO) alone for eighteen months. An initial rapid decrease of
      serum ferritin was observed in all six patients when the loading dose of EPO was
      given. Three patients (Cases 4, 5, 6) who suffered from chronic blood loss
      maintained a continuous decline of serum ferritin in the subsequent stage of
      maintenance dose EPO therapy, however, the decrease of serum ferritin became
      sluggish under a maintenance dose in the other three patients (Cases 1, 2 and 3).
      The serum ferritin eventually decreased to a satisfactory level (975-1761 mu g/L)
      in Cases 4, 5 and 6, whereas it remained high (4232-8196 mu g/L) in Cases 1, 2,
      and 3 who had higher basal levels of serum ferritin (5641-15704 mu g/L) and a
      plateau of response under a maintenance dose of EPO. These three patients were
      then treated with EPO and phlebotomy. Their serum ferritin decreased quickly from
      6752 +/- 1264 mu g/L to 2454 +/- 482 mu g/L after six months of phlebotomy
      therapy; it was a dramatic improvement in contrast to the stagnant response under
      a maintenance dose of EPO alone. Our experience indicates that EPO therapy alone
      has its limitations in treating severe iron overload. Although there is an
      initial rapid decrease of serum ferritin during the period of the loading dose,
      the response might become stagnant during the period of maintenance dose.
      Phlebotomy effectively eliminated the excessive iron stores in these refractory
      cases. Therefore, we suggest that phlebotomy be considered in severe iron
      overload if a stagnant response is observed under a maintenance dose EPO therapy.

PMID- 8521336
TI  - Ilizarov femoral lengthening in adults.
AB  - From January 1990 to December 1991, we treated 12 cases of length discrepancy due
      to femoral inequality with the technique of Ilizarov femoral lengthening. The
      patients' ages ranged from 20 to 33 years (average, 28 years). Of these, nine
      patients were men and three were women. Corticotomy was performed either at the
      distal metaphysis or at the junction of distal metaphysis and diaphysis. After a
      latency of seven to ten days, distraction commenced at a rate 0.25 mm every six
      to twelve hours. Bone generation was obtained in all patients without the need of
      bone grafting. The average length gained in femoral bone was 4.7 cms (range, 3 to
      7 cms). The average duration of total treatment was 10.1 months (range, 7 to 15
      months). The healing index was 2.2 (number of months per 1 cm elongation) on
      average. All patients were satisfied with the results, but all felt that it was
      an uncomfortable procedure. According to our experience, we conclude that the
      method of Ilizarov is an useful technique for femoral lengthening. However, it is
      an uncomfortable and tedious procedure.

PMID- 8521337
TI  - Osteosarcoma of jaw: the experience of Chang Gung Memorial Hospital.
AB  - Seven cases with Osteosarcoma (OS) of the jaw were retrospectively reviewed.
      There were five female and two male patients. Their ages ranged from 14 to 57
      years with a mean of 39 years. Seventy-one percent of the patients were older
      than 30 years old. Jaw swellings were the most frequent complaints occurring on
      an average of 3 months before diagnosis. Four cases occurred in mandible and
      three cases developed from maxilla. Most cases were lytic lesions on
      roentgenography. Four were osteoblastic, 2 were chondroblastic, and 1 was
      histologic classification. Six of the 7 cases received surgery. Postoperatively,
      3 of them received both radiotherapy and chemotherapy, 1 received chemotherapy
      only and 1 received radiotherapy only. One case received palliative chemotherapy
      only because of the locally far advanced disease. Four cases died of regional
      failure without any metastatic lesions (survival ranged from 5 months to 22
      months). Two cases survived more than 4 years without any recurrence. The median
      survival time was 22 months. We concluded that OS of the jaw has different
      natural courses from OS of the long bones and the regional failure seems to be
      the main problem in jaw OS.

PMID- 8521338
TI  - Villous adenoma of the urinary bladder: a case report.
AB  - A case of villous adenoma of the urinary bladder is described. The patient, a 57
      year-old Chinese male, presented with a long-term history of urethral stricture
      disease secondary to gonorrhea urethritis. On cystoscopic examination, a mucin
      secreting papillary tumor, measuring 3 x 2 cm was noted at the bladder neck.
      Microscopically, there were papillary fronds of mucin-secreting columnar cells
      with varying degrees of piling up. The relationships between chronic irritation
      of the urinary bladder, cystitis glandularis, intestinal metaplasia, villous
      adenoma and adenocarcinoma were discussed.

PMID- 8521339
TI  - Idiopathic common bile duct perforation: a case report.
AB  - Spontaneous or idiopathic perforation of the bile duct (IPBD) in neonates and
      infants is a rare disease. An 1-year-5-month-old female child admitted with
      progressive abdominal distension and generalized jaundice. She had previously
      been treated for bacterial peritonitis at another hospital by using strong
      antibiotics. Abdominal tapping revealed bilious ascites suggesting a possible
      biliary tree perforation and was later confirmed by the scintigraphy study. She
      was subsequently operated and recovered uneventfully. The mode of presentation,
      diagnosis and treatment are described and the literature reviewed.

PMID- 8521340
TI  - Retrieval of a pin from the airway: a case report.
AB  - Inhalation of foreign body in children is extremely hazardous, since the caliber
      of the tracheobronchial tree is small in children and the technique of
      bronchoscopic extraction is very demanding. The problem is even more complicated
      in handling rare foreign bodies, since the bronchoscopic procedure may be
      prolonged and inaccurate. Presented here is a case of pin aspiration. The long
      and pointed pin is quite impossible to remove. In this article, the course of
      bronchoscopy removal of the pin was described and the technical aspects of rigid
      bronchoscopy in handling pointed objects were cited in detail.

PMID- 8521341
TI  - Concurrent colon polyp with angiodysplasia causes lower gastrointestinal
      bleeding: a case report.
AB  - Angiodysplasia is an important cause of gastrointestinal bleeding which occurs
      mostly common in the right side of the colon, usually in the elderly but
      sometimes in younger adults. Herein, a case of rare clinical association
      adenomatous colonic polyp with submucosal angiodysplasia in a forty year old man,
      who had repeated intestinal bleeding, is reported. We think colon polyps inducing
      intestinal blood loss may be caused by unidentified angiodysplasia. The diagnosis
      of these lesions is very difficult, so mesenteric angiography is recommended.
      Although various therapeutic methods were suggested, in patients who have
      repeated bleeding or are chronic anemics, resection of the involved segment of
      the bowel is the treatment of choices.

PMID- 8521342
TI  - Multiple sclerosis in children: report of two cases.
AB  - Multiple sclerosis is a disease of white matter in the central nervous system
      characterized by clinically relapsing and remitting course. It is rare in
      children and the mean age of onset is about 30 years. To establish diagnosis, one
      must note that white matter lesions are disseminated in time and place. We report
      two female patients with recurrent episodes of headaches, seizures, hemiparesis,
      and optic neuritis since childhood. Four of the five CT scans done during the
      relapse attacks in these two patients showed negative findings. The only one
      abnormal finding was decreased density in the white matter over the right
      frontoparietal area. MRI showed multiple focal patches of high signal intensity
      in white matter on T2-weighted image in Case 1, and increased signal intensity on
      the right paraventricular region on T2-weighted image in Case 2. Now, MRI is the
      neuroimaging test of choice, and makes early diagnosis possible. It is useful in
      assessing the extent of multiple sclerosis and in monitoring the clinical course.

PMID- 8521343
TI  - Pyopneumothorax associated with unsuspected endobronchial foreign body: a case
      report.
AB  - Chronic foreign body aspiration may cause a variety of complications. Nonspecific
      clinical presentations and chest radiographic manifestations often result in
      misdiagnosis or delayed diagnosis. We report an unusual complication of chronic
      foreign body aspiration--pyopneumothorax--in a 52-year-old patient presenting
      with productive cough and intermittent fever for more than 3 months. Obstructive
      pneumonia was highly suspected from the computed tomographic scan of the chest.
      Flexible fiberoptic bronchoscopy demonstrated a fish bone in the bronchial tree.
      The bone was successfully removed by forceps. Thoracotomy was done later to ensue
      adequate drainage of the pyopneumothorax. We report this case for ongoing
      education to increase the index of suspicion.

PMID- 8521344
TI  - [Torsion of gallbladder in childhood: a case report].
AB  - A 9-year-old girl presented with severe intermittent upper abdominal pain and
      bilious vomiting for 1 day. Abdominal echography demonstrated severe distension
      of the gallbladder with marked change in its long axis. Torsion of the
      gallbladder was suspected preoperatively. Counter-clockwise rotation of the
      gallbladder around its neck for more than 180 degrees with necrosis of the whole
      gallbladder was found during the emergency laparotomy. Choleystectomy was
      performed smoothly after detorsion of the gallbladder. The postoperative recovery
      was uneventful. Although torsion of the gallbladder is rarely reported in
      children, we should keep this possibility in mind as a differential diagnosis of
      acute abdomen.

PMID- 8521345
TI  - [Invagination of vermiform appendix in an asymptomatic adult: a case report].
AB  - Invagination of the vermiform appendix (appendiceal intussusception) is a very
      rare disease. Most cases occur in patients under 10 years of age. The clinical
      presentation of invagination of the vermiform appendix is extremely variable and
      most cases are symptomatic. The pathogenesis of invagination of appendix is still
      not clear, but some precipitating factors have been identified. Herein, we report
      one case of primary invagination of the vermiform appendix in a adult without any
      symptom. Etiology, precipitating factor, clinical presentation, classification,
      and diagnosis method are discussed.

PMID- 8521347
TI  - Effect of time of year, weather, and the pattern of auction market sales on fatal
      fibrinous pneumonia (shipping fever) in calves in a large feedlot in Alberta
      (1985-1988).
AB  - A total of 58,885 spring-born calves entering a large commercial feedlot in
      southwestern Alberta were studied to examine the associations between shipping
      fever mortality and the pattern of calf sales at the auction markets, time of
      year, and weather. The observational study followed calves purchased from 42
      auction markets in the 4 western provinces between September 1 and December 31 in
      each of the years from 1985 to 1988. Calf sales at the auction markets
      consistently peaked during the last week of October and the first week of
      November. Calves entering the feedlot in November had a risk of fatal shipping
      fever 2 to 8 times greater than calves entering in September or December. The
      pattern was the same for all 4 years, with maximum risk occurring 2 to 4 weeks
      after the peak time for calf sales at the markets. A number of factors could have
      contributed to this pattern, including changes in transport truck availability,
      changes in the density of calves at the markets, changes in population dynamics
      at the feedlot that affected feedlot crew efficiency, and weather. The finding
      that the risk of fatal shipping fever appears to increase significantly as the
      feedlot fills with calves in the fall deserves the attention of feedlot owners,
      so they can design their treatment strategies appropriately, and of researchers,
      who may gain useful knowledge about the natural history of the disease by
      investigating why this change in risk occurs.

PMID- 8521346
TI  - Isolation, serotypes, and virulence-associated properties of Yersinia
      enterocolitica from the tonsils of slaughter hogs.
AB  - The objectives of this study were to determine the carriage rate of Yersinia
      enterocolitica in the tonsils of slaughter hogs, and to characterize them with
      regard to phenotypic and virulence-associated properties. Of 202 pigs examined
      from an abattoir in Prince Edward Island, 85 were culture positive for Y.
      enterocolitica. Sixty-seven percent of isolates belonged to serotype O:3, and 20%
      were serotype O:5. All isolates produced urease and 95% of O:3 isolates showed
      virulence-associated characters of autoagglutination at 37 degrees C and lack of
      fermentation of esculin and salicin. All isolates were tested for crystal violet
      binding, calcium dependency, and virulence plasmids. Eight isolates (5 belonging
      to serotype O:3, 2 belonging to O:5,27, and 1 belonging to O:7,8) were tested in
      addition for the production of heat-stable enterotoxin (ST), and iron-chelating
      siderophores. Of the 57 O:3 isolates, 93% were positive for crystal violet
      binding and calcium dependency and 98% possessed a 40-45 MDa plasmid. Four of the
      5 O:3 isolates tested for ST related to Escherichia coli STa in a commercial
      enzyme immunoassay were positive. Six of the 8 isolates belonging to 3 different
      serotypes produced large orange halos around the colonies on a chrome-azurol-s
      agar assay medium, for siderophores. Antimicrobial susceptibility tests of all 85
      isolates against 16 drugs showed 100% susceptibility against 12 drugs, including
      trimethoprim-sulfamethoxazole and tetracycline.

PMID- 8521348
TI  - A comparative study of bovine and ovine Haemophilus somnus isolates.
AB  - Bacterial isolates (including 17 Haemophilus somnus isolates and an H. somnus
      like isolate) from asymptomatic or diseased cattle and sheep, were evaluated for
      markers associated with virulence and host predilection. The isolates were
      separated into 6 distinct biovariants, 3 for sheep and 3 for cattle, based on
      reactions in a battery of 21 test media. Three bovine isolates associated with
      disease caused hemolysis of bovine blood. The rest of the isolates did not
      hemolyze either bovine or ovine erythrocytes. Protein profiles of all H. somnus
      isolates were similar with the exception of the major outer membrane proteins
      (MOMPs). The MOMPs of isolates associated with disease in cattle had a relative
      molecular weight of approximately 41 kDa compared with 33 kDa for the MOMPs of
      isolates from asymptomatic cattle. The MOMPs from sheep isolates were either
      slightly higher or lower than the 41 kDa MOMPs of bovine isolates. Major antigens
      detected by Western blotting were similar in all isolates except the H. somnus
      like isolate. An immunodominant 40 kDa antigen was conserved in all H. somnus
      isolates. Antibodies to this antigen have previously been found to be protective
      in cattle and may also be protective for sheep. Marked differences between cattle
      and sheep isolates were revealed by use of restriction enzyme analysis, which
      separated the isolates into 12 ribotypes and 15 unique DNA profiles. Thus, cattle
      and sheep isolates in this collection had distinctive differences in biochemical
      reactions, MOMP profiles, and DNA analyses. Such differences have potential value
      for epidemiological studies and may also be used to evaluate host specificity of
      H. somnus isolates.

PMID- 8521349
TI  - Comparison of protection of experimentally challenged cattle vaccinated once or
      twice with a Pasteurella haemolytica bacterial extract vaccine.
AB  - Three groups of calves (15-18 per group) were injected twice at a 3-week interval
      with 2 doses of phosphate buffered saline (PBS, CONTROL group), 2 doses of
      PRESPONSE, a Pasteurella haemolytica A1 bacterial extract vaccine (PRESPONSE-2
      group) or 1 dose of PBS followed by a 2nd vaccination with 1 dose of PRESPONSE
      (PRESPONSE-1 group). Three weeks after the 2nd vaccination, the calves were
      challenged intratracheally with P. haemolytica A1. Calves were evaluated
      clinically for 3 days prior to challenge and for 5 days after challenge. Six days
      postchallenge, calves were either euthanized or sent to slaughter and the lungs
      were evaluated for percent pneumonic tissue. There was a significant effect of
      single or double application of vaccine on clinical scores (P = 0.0409). Percent
      pneumonic tissue at necropsy was significantly affected by vaccine group (P =
      0.014). Calves in the CONTROL group had significantly higher percent pneumonic
      tissue after arcsine transformation (45.30%) than calves in any group receiving
      PRESPONSE, regardless of vaccination frequency (25.18% and 25.78%, for calves
      receiving 2 doses or 1 dose of PRESPONSE, respectively). Both serum toxin
      neutralizing and direct agglutinating titers were negatively correlated with
      percent pneumonic tissue. Most importantly, 1 dose of PRESPONSE was as efficient
      as 2 doses at eliciting a protective immune response. It is concluded that the
      presence of P. haemolytica as a natural commensal in the upper respiratory tract
      of the calf can effectively prime the animal, and allow the animal to respond in
      an anamnestic nature to only 1 dose of this vaccine.

PMID- 8521350
TI  - Bactericidal effects of ozone at nonspermicidal concentrations.
AB  - A study was conducted to assess the use of ozone (O3) to control pathogens or
      contaminants of concern to animal breeders and regulatory officials. In separate
      experiments, samples of fresh bovine semen and Pseudomonas aeruginosa,
      Escherichia coli, or Campylobacter fetus subsp. venerealis were diluted with
      antibiotic-free milk (10(6) sperm and 10(6) organisms/mL of diluted semen),
      exposed in the previous day to a constantly monitored level of 5, 10, 15, or 20
      micrograms/mL of O3 for 3-5 min. After 10 min at 30 degrees C, sperm motility was
      assessed and the samples cooled to 5 degrees C. Two and 18 h after the beginning
      of cooling, aliquots of each semen sample were evaluated for motility and
      cultured for organisms. Reductions were observed in P. aeruginosa and E. coli
      colony counts of 2 logs, and in C. fetus of 5 logs, after exposure for 2 h to O3
      at a concentration of 5 micrograms/mL that had a moderate effect on sperm
      motility (reduction of 20%). Fewer than 100 colonies, i.e., a 4 logs reduction of
      all bacteria, were counted after dilution with ozonized-treated milk at 20
      micrograms/mL of O3. However, this concentration of O3 reduced sperm motility by
      50% 10 min after dilution. The results of these experiments indicate that a
      concentration and exposure time to O3 can be selected to reduce P. aeruginosa, E.
      coli, and C. fetus in contaminated bull semen diluted with milk while having only
      minimal effects on sperm motility.

PMID- 8521351
TI  - Pathogenesis of in utero infection in porcine fetuses with porcine reproductive
      and respiratory syndrome virus.
AB  - Porcine fetuses were exposed in utero to porcine reproductive and respiratory
      syndrome virus (PRRSV) at stages of gestation ranging from 34 to 85 days and
      examined 17 to 31 days later to determine the effect of gestational age on fetal
      susceptibility. For each of the 8 litters tested during the study, all of the
      fetuses of 1 horn of the uterus were exposed to virus by intraamniotic injection;
      those of the other horn were exposed similarly to a sham inoculum that consisted
      of sterile cell culture medium. Viral infectivity titers associated with fetal
      tissues collected at necropsy indicated that, regardless of gestational age, the
      virus had replicated in fetuses exposed intraamniotically. In addition, virus had
      also spread and replicated in sham-inoculated littermates in 3 litters. On the
      basis of these findings it appears that there may be little or no temporal
      difference in fetal susceptibility to infection with PRRSV. If so, the lack of
      early fetal death as a commonly recognized feature of naturally occurring cases
      of PRRS may be due to a greater resistance of early gestational fetuses to the
      lethal effects of PRRSV, as suggested by this study, and/or a greater likelihood
      of transplacental infection during late gestation.

PMID- 8521352
TI  - Influence of vulvar hygiene on cytology of vaginal smears after sham artificial
      insemination in sows.
AB  - The description of vaginal cytology in the sow in relation to artificial
      insemination (AI) has never been reported. Poor vulvar hygiene is frequently
      imputed as a cause for the development of endometritis after AI and could thus
      enhance the inflammatory response of the genital tract. The goal of this study
      was to use cytology as an objective tool to evaluate the vulvar hygiene during
      sham AI. Sixty-eight sows were matched according to their parity and week of
      mating and divided into 2 groups: treatment sows (CVS) had their vulva cleaned
      with a 1:2000 Hibitane solution and control sows (SVS) had theirs soiled with
      feces. Both groups of sows were inseminated twice with saline following this
      vulvar treatment, once at detection of estrus and a 2nd time 24 hours later.
      Vestibular smears were taken before each AI, and vaginal smears were taken after
      each AI from the material present on the insemination spirette. Cytological
      smears were described by the predominant type of cells, namely epithelial,
      neutrophil, or no predominance. Results showed no significant differences between
      the 2 groups and no evolution in the predominance of neutrophils from the 1st to
      the 2nd AI (P > 0.05). The pooled results from the 2 groups showed an increase in
      cellularity from the 1st to the 2nd AI (P > 0.05). Neither the cellularity nor
      predominant cell type in vestibular or vaginal smears from estrus sows are
      predictors of vulvar hygiene during sham AI (P > 0.05).

PMID- 8521353
TI  - Enzootic pneumonia: comparison of cough and lung lesions as predictors of weight
      gain in swine.
AB  - A prospective cohort study was undertaken in a commercial swine herd to determine
      the relationship between weight gain and the occurrence of enzootic pneumonia
      (EP). Estimates of the association between EP and weight gain were obtained from
      multiple linear regression models, using coughing episodes or slaughter checks as
      indicators of EP status. Models were estimated for pigs in 2 different age
      groups: roasters (n = 1084, sold at 32 to 50 kg) and market hogs (n = 1162, sold
      at 100 to 110 kg). The relationship between presence of lung lesions at slaughter
      and previous coughing episodes was also investigated. Throughout the study
      period, clinical evaluations were performed weekly, and coughing episodes
      recorded for each pig. Lungs were inspected at slaughter, and scores were
      expressed as the percentage of the lung with gross pneumonic lesions. Coughing
      and lung scores were significantly correlated, after adjusting for other
      covariates (R = 0.32 and 0.59, respectively, for market hogs and roasters).
      However, the agreement beyond chance between coughing history and lung lesions at
      slaughter was poor among both roasters and market hogs (kappa = 0.17 and 0.07,
      respectively). Although very specific, weekly assessment of coughing was not a
      sensitive indicator of lung lesions at slaughter. In multiple regression, lung
      score was a highly significant predictor of lower final weight in pigs of both
      age groups (P < 0.001 in the selected regression models).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8521354
TI  - Assessment of glycosaminoglycan concentration in equine synovial fluid as a
      marker of joint disease.
AB  - A modification of a colorimetric assay was used to determine synovial fluid total
      and individual sulphated-glycosaminoglycan concentration in various clinical
      presentations of joint disease in horses. Concentrations of synovial fluid and
      serum sulphated-glycosaminoglycan (GAG) were measured by the 1,9
      dimethylmethylene blue (DMMB) dye assay in normal horses (n = 49), horses with
      acute (n = 26) or chronic (n = 27) joint disease (defined by clinical,
      radiographic, and clinicopathological parameters), and horses with cartilaginous
      lesions at diagnostic arthroscopy, but with normal radiographs and synovial fluid
      (n = 9). Horses with acute joint disease were subdivided into moderate acute (n =
      21) and severe acute (n = 5) joint disease on the basis of synovial fluid
      analysis and clinical examination. Horses with chronic joint disease were
      subdivided into mild chronic (n = 9), moderate chronic (n = 10), and severe
      chronic (n = 8) joint disease on the basis of synovial fluid analysis, clinical
      examination, and radiographic findings. The concentrations of chondroitin
      sulphate (CS) and keratan sulphate (KS) were analyzed in each sample following
      sequential enzymatic digestion of the sample with chondroitinase or keratanase.
      In addition, the concentration of hyaluronate (HA) in each sample was determined
      by a colorimetric assay following digestion of the sample with microbial
      hyaluronidase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521355
TI  - Cardiopulmonary effects of hypercapnia during controlled intermittent positive
      pressure ventilation in the horse.
AB  - The cardiopulmonary effects of eucapnia (arterial CO2 tension [PaCO2] 40.4 +/-
      2.9 mm Hg, mean +/- SD), mild hypercapnia (PaCO2, 59.1 +/- 3.5 mm Hg), moderate
      hypercapnia (PaCO2, 82.6 +/- 4.9 mm Hg), and severe hypercapnia (PaCO2, 110.3 +/-
      12.2 mm Hg) were studied in 8 horses during isoflurane anesthesia with volume
      controlled intermittent positive pressure ventilation (IPPV) and neuromuscular
      blockade. The sequence of changes in PaCO2 was randomized. Mild hypercapnia
      produced bradycardia resulting in a significant (P < 0.05) decrease in cardiac
      index (CI) and oxygen delivery (DO2), while hemoglobin concentration (Hb), the
      hematocrit (Hct), systolic blood pressure (SBP), mean blood pressure (MBP),
      systemic vascular resistance (SVR), and venous admixture (QS/QT) increased
      significantly. Moderate hypercapnia resulted in a significant rise in CI, stroke
      index (SI), SBP, MBP, mean pulmonary artery pressure (PAP), Hct, Hb, arterial
      oxygen content (CaO2), mixed venous oxygen content (CvO2), and DO2, with heart
      rate (HR) staying below eucapnic levels. Severe hypercapnia resulted in a marked
      rise in HR, CI, SI, SBP, PAP, Hct, Hb, CaO2, CvO2, and DO2. Systemic vascular
      resistance was significantly decreased, while MBP levels were not different from
      those during moderate hypercapnia. No cardiac arrhythmias were recorded with any
      of the ranges of PaCO2. Norepinephrine levels increased progressively with each
      increase in PaCO2, whereas plasma cortisol levels remained unchanged. It was
      concluded that hypercapnia in isoflurane-anesthetized horses elicits a biphasic
      cardiopulmonary response, with mild hypercapnia producing a fall in CI and DO2
      despite an increase in MBP, while moderate and severe hypercapnia produce an
      augmentation of the cardiopulmonary performance and DO2.

PMID- 8521356
TI  - Cardiorespiratory effects of hemic versus nonhemic prime during and immediately
      following mitral valve replacement in dogs.
AB  - In order to limit the hemodilution effect during cardiopulmonary bypass (CPB) in
      low weight animal patients, blood is often used as a component of the prime
      solution. This study was undertaken to evaluate the effects of the addition of
      blood to the prime solution on the hemodynamic and respiratory parameters during
      and following mitral valve replacement in dogs. Ten dogs were randomly assigned
      to receive either a hemic (HP), 75% blood component, or a nonhemic prime (NP)
      solution. The hemodilution was 5 +/- 4% and 25 +/- 10% for the HP and NP groups,
      respectively. Cardiopulmonary measurements were taken 20 minutes before
      initiating CPB, during CPB, and 20 min after termination. The hematocrit level,
      the hemoglobin concentration, and the arterial oxygen content were significantly
      lower in the NP group during and following CPB. However, the systemic oxygen
      transport index was not significantly different between the NP group (355 +/- 87
      mL/min/m2) and the HP group (546 +/- 155 mL/min/m2) following CPB. Our study
      indicates that, in normal dogs undergoing hemodilution from a nonhemic prime
      solution, the cardiovascular function is able to maintain the systemic oxygen
      transport in the period immediately following mitral valve replacement.

PMID- 8521357
TI  - A physical map of the 85 kb virulence plasmid of Rhodococcus equi 103.
AB  - A physical map of the 85 kb virulence plasmid pOTS from Rhodococcus equi 103 was
      constructed. The restriction map contains 2 AsnI, 5 BglII, 9 EcoRI, 4 HindIII,
      and 3 XbaI sites. The positions of the EcoRI and HindIII of pOTS are identical to
      that of the 85 kb virulence plasmid of R. equi ATCC 33701 reported recently by
      others. EcoRI restriction fragment sizes were similar in the 85 kb plasmids
      isolated from 4 horse derived R. equi but, except apparently for the 28.3 and
      possibly 2.0 and 1.5 kb fragments, were different in an 80.1 kb plasmid isolated
      from a pig source R. equi.

PMID- 8521358
TI  - Antigenic comparison of Canadian and US isolates of porcine reproductive and
      respiratory syndrome virus using monoclonal antibodies to the nucleocapsid
      protein.
AB  - Fifteen Canadian field isolates of porcine reproductive and respiratory syndrome
      (PRRS) virus from Quebec and Ontario were compared with 5 US PRRS virus (PRRSV)
      isolates and with the European Lelystad isolate using monoclonal antibodies
      (MAbs) SDOW17, EP147, and VO17 directed to the 15-kDa nucleocapsid protein of
      PRRSV. All Canadian and US isolates tested by indirect immunofluorescence were
      recognized by the 3 MAbs, and individual titers of MAbs towards Canadian and US
      PRRSV isolates were similar as well. In contrast, the Lelystad virus isolate
      reacted only with the SDOW17 MAb and showed no reactivity with either EP147 or
      VO17. The reactivity pattern with these MAbs suggests that the Canadian isolates
      of PRRSV tested are antigenically similar to US isolates of PRRSV, and that these
      North American isolates share highly conserved epitopes on the 15-kDa
      nucleocapsid protein that clearly differentiate them from the European Lelystad
      virus isolate.

PMID- 8521359
TI  - Prevalence of serotypes G6 and G10 group A rotaviruses in dairy calves in Quebec.
AB  - Fecal samples from diarrheic and nondiarrheic dairy calves (1 to 3 weeks old)
      from 12 regions of Quebec, collected between 1992 and 1994, were screened for
      group A bovine rotavirus (BRV) using a combination of 2 VP6-specific monoclonal
      antibodies (MAbs) in an enzyme-linked immunosorbent assay (ELISA). The overall
      prevalence of BRV infection was 26.4% (107/405). In diarrheic calves, BRV
      infection reached 74.3% (55/74), but only 15.7% (52/331) in nondiarrheic calves.
      BRV-positive samples were serotyped by enzyme-linked immunosorbent assay (ELISA)
      using G6 and G10 specific MAbs. The analysis of 107 field samples revealed that,
      in diarrheic calves, 34.5% (19/55) were G6, 27.2% (15/55) were G10, 9% (5/55)
      were G6 and G10 positive, and 29.9% (16/55) were G6 and G10 negative. In
      nondiarrheic calves, 19.2% (10/52) were G6, 19.2% (10/52) were G10, 7.6% (4/52)
      were G6 and G10 positive, and 53.6% (28/52) were G6 and G10 negative. Rotavirus
      dsRNA was extracted from BRV-positive samples and examined by polyacrilamide gel
      electrophoresis (PAGE). Of 107 samples tested, 74 (69.1%) were positive, and all
      the samples demonstrated a typical group A rotavirus migration pattern.

PMID- 8521360
TI  - Comparison of direct and indirect blood pressure measurements in anesthetized
      dogs.
AB  - The precision and accuracy of an indirect oscillometric blood pressure
      measurement technique (Dinamap 8100) was assessed in 11 anesthetized Beagle dogs
      weighing 8 to 11.5 kg. Direct blood pressure measurements were made by
      catheterization of the lingual artery, and simultaneous indirect measurements
      were determined by placing a cuff over the median artery (midradial area). Blood
      pressure measurements at 2 different planes of anesthesia (light and deep) were
      recorded in triplicate. At a light plane of anesthesia, the Dinamap 8100
      underestimated diastolic and mean arterial pressure, and at a deep anesthetic
      plane overestimated systolic pressure. The indirect technique had good
      repeatability of systolic pressures. Regression analysis for the 2 techniques
      showed excellent correlation (r = 0.93). The results indicate that the indirect
      oscillometric blood pressure measurement technique provides a good estimate of
      systolic, diastolic, and mean arterial pressure in dogs weighing 8-11.5 kg.

PMID- 8521361
TI  - Mycobacterial disease: a historical and epidemiologic perspective.

PMID- 8521362
TI  - Microbiology and classification of mycobacteria.

PMID- 8521363
TI  - Epidemiology of mycobacterial diseases.

PMID- 8521364
TI  - Toxic effects and drug interactions of antimycobacterial therapy.

PMID- 8521365
TI  - Leprosy.

PMID- 8521366
TI  - Cutaneous tuberculosis.

PMID- 8521367
TI  - Unusual cutaneous mycobacterial diseases.

PMID- 8521368
TI  - Cutaneous infections with rapidly growing mycobacteria.

PMID- 8521369
TI  - Mycobacterium marinum.

PMID- 8521370
TI  - Diseases caused by Mycobacterium scrofulaceum.

PMID- 8521371
TI  - Mycocutaneous atypical mycobacterial infections in acquired immunodeficiency
      syndrome.

PMID- 8521372
TI  - The use of mucin-specific monoclonal antibodies and lectins in the detection of
      tumor-associated serum markers in gynecological cancer.
AB  - The use of the mucin-specific lectin from Sambucus sieboldiana (SSAM) in the
      detection of tumor-associated serum antigens produced by patients with ovarian,
      cervical, and uterine cancer was investigated. Two-site assays were developed
      which used either SSAM or the MUC1 core protein-specific monoclonal antibody
      (mab) BC2 as capture, and biotinylated SSAM to detect bound mucin (SSAM and
      BC2SSAM assays respectively). These new assays were compared to the CA125 assay,
      and another assay for MUC1 (CASA), which utilizes the core protein reactive mabs
      BC2 and BC3. some asymptomatic women and patients with benign disease showed very
      high levels in the SSAM assay, while this was not the case in the other assays.
      When cutoff levels were set to exclude healthy women and patients with benign
      disease, the levels of detection in patients with ovarian cancer were 51% with
      CASA (> 6.7 units/ml), 71% with CA125 (> 250 units/ml), and 38% with BC2SSAM (>
      8.6 units/ml). The levels of detection in cervical and uterine cancer patients
      were 28% and 25% with CASA, 0% and 8% with CA125, and 28% and 25% with BC2SSAM
      respectively. Of particular interest was the very different spectrum of
      reactivity observed with the CASA and BC2SSAM assays which use the same capture
      mab, indicating that each assay detects different glycoforms of the MUC1 mucin.
      Indeed, when used in combination, the CASA and BC2SSAM assays gave 62% of ovarian
      cancer patients, and 50% of cervical or uterine cancer patients with elevated
      marker levels. The additional use of BC2SSAM gave no advantage over the combined
      use of the CASA and CA125 assays in ovarian cancer, with 80% of patients
      detected, but the CASA/BC2SSAM combination was particularly useful in the
      cervical and uterine cancers due to the low level of detection with CA125. In
      fact, the additional use of CA125 gave no advantage over the CASA/BC2SSAM
      combination in these patients. Furthermore, the BC2SSAM assay may also be useful
      in monitoring patients with high preoperative BC2SSAM levels (> 10 units/ml),
      since this assay predicted recurrence in 5/5 cases, and was negative in all cases
      with no evidence of disease. Furthermore, the performance of this assay in
      monitoring these patients was equal or superior to CA125 and CASA.

PMID- 8521373
TI  - Microwave induced alteration in the neuron specific enolase gene expression.
AB  - Exposure of pNGE7, a recombinant clone containing the coding and regulatory
      sequences for the expression of neuron specific enolase gene, cells to
      electromagnetic radiations (915 MHz, 16 Hz AM, SAR 0.05 mW/kg) resulted in the
      elevation of neuron specific enolase (NSE), a diagnostic marker for neuron and
      lung cancer. Using ion-exchange chromatography we separated the neuron specific
      enolase activity from the non-neuronal enolase (NNE) activity and observed an
      alteration in the expression of neuron specific enolase and non-neuronal enolase.
      The clinical applications of the present studies have been discussed.

PMID- 8521374
TI  - DXR depresses the alpha-actinin-induced formation of actin bundles.
AB  - The filament-to-filament interactions in cardiac alpha-actinin/F-actin mixtures
      were investigated in the presence of doxorubicin. Stoichiometrical concentrations
      of the drug in the assembly medium inhibit the growth of alpha-actinin/F-actin
      three-dimensional structures, as shown by low speed centrifugation, light
      scattering, A320nm, electron microscopy and low shear viscosity tests. DXR
      induced short actin bundle formation could be related to the inhibition of the
      bundle elongation mechanism, and furthermore, could account for some
      morphological evidences in DXR-treated living cells. Our results support both the
      formation pathway of actin bundles as proposed by Stokes and DeRosier (1991), and
      the observations of Molinari et al. (1990) on the human CG5 cell line.

PMID- 8521375
TI  - Homeostatic derangement in the CBA rodent host during the growth of the CaNT
      tumor.
AB  - The purpose of this study was to evaluate some indicators of the pathogenesis of
      cancer cachexia in which the growth of the CaNT tumor markedly alters the
      metabolism and induces measurable biochemical changes of the host. An increase of
      hexokinase and lactate dehydrogenase activities with tumor volume, coupled with
      the decline of oxygen consumption are shown in this work. Furthermore changes in
      the mean spin lattice and spin-spin relaxation time values of the tumor provide
      additional information of the abnormal cellular spatial and metabolic
      relationships that exists within the tumor. In the liver of the host, the
      augmentation of the oxygen uptake and specific activities of lactate
      dehydrogenase and fructose-1,6-diphosphatase shown in this work, reflecting an
      increase in the glucose metabolism rate and thus, energy expenditure of the host.
      This may envisage some correlation with the onset of biochemical changes in the
      homeostatic derangement in the host during the fast growth of the tumor.

PMID- 8521377
TI  - Urinary excretion of glycosaminoglycans in patients with superficial bladder
      tumors.
AB  - Urinary glycosaminoglycan/creatinine (GAG/Cr) ratio was determined in 73 patients
      with superficial bladder tumors and 34 healthy volunteers. While the mean GAG/Cr
      value in the tumor group was higher than the control group (11.25 +/- 5.36 vs.
      10.11 +/- 2.67) this difference was not statistically significant. However,
      comparing the urinary GAG/Cr ratio of T1, Grade III and recurrent tumors with the
      control group revealed statistically significant results (p < 0.01, p < 0.001 and
      p < 0.02 respectively). Therefore, the urinary GAG/Cr ratio determination in the
      follow-up of these patients may be used as noninvasive procedure and high levels
      may be signs of higher grade, higher stage disease.

PMID- 8521376
TI  - Expression of a 118 Kd protein in colon carcinoma cells that is immunologically
      related to PLC-gamma 1 and is augmented by serum-free conditions.
AB  - Immunoprecipitation of cell lysates from serum-starved HCT-8 colon carcinoma
      cells with monoclonal antibodies raised to PLC-gamma 1 precipitates proteins
      which can be detected by immunoblotting; the 148 Kd PLC-gamma 1 and a smaller
      protein of approximately 118 Kd (p118). Expression of p118 is suppressed in cells
      grown in serum but is present 8 to 12 h after cells are placed in serum-free
      medium. Conversely, serum-starved cells that express this protein suppress it 6
      to 8 h after exposure to 10% fetal calf serum. Pulse chase experiments indicate
      that the protein is not a degradation product of PLC. This protein has thus far
      been detected only in human carcinoma cells and not in normal or transformed
      fibroblasts. Although the protein has not been identified, its expression pattern
      may suggest a role contributing to the serum-independent nature of human
      carcinoma cell lines.

PMID- 8521378
TI  - Effects of exogenous transglutaminase on spreading of human colorectal carcinoma
      cells.
AB  - Using pre-confluent cultures of a human colon tumor cell line deficient in
      transglutaminase (LS174T cells), we have investigated the effect of adding
      exogenous transglutaminase (TGA) on cell spreading. The cells were plated at
      either 4.5 x 10(5) cells per well (low-seeded cultures) or 9 x 10(5) cells per
      well (high-seeded cultures) in 24-well dishes and treated for either 1 or 4 days
      (low- and high-seeded cultures respectively) under following conditions: Chee's
      Essential Medium (CEM) + 10% fetal calf serum (FCS); CEM + 10% FCS + TGA; CEM +
      10% FCS + dithiothreitol (DTT) + CaCl2; CEM + 10% FCS + DTT + CaCl2 + TGA.
      Photomicrography of the cells after these treatments revealed that in both low-
      and high-seeded cultures, TGA inhibited the spreading of the cells both in the
      presence and absence of DTT and calcium. Individual colony sizes were
      significantly smaller in the presence of TGA. This phenomenon may be related to
      the ability of TGA to promote cell interactions with the underlying tissue
      matrices and metastasis.

PMID- 8521379
TI  - Synergistic action of taxol and tiazofurin in human ovarian, pancreatic and lung
      carcinoma cells.
AB  - Since taxol (NSC 125975) and tiazofurin (NSC 286193) attack at two different
      sites in microtubular synthetic processes, we tested the rationale that the two
      drugs might be synergistic in human ovarian (OVCAR-5), pancreatic (PANC-1) and
      lung carcinoma (H-125) cells and in rat hepatoma 3924A cells. In human OVCAR-5,
      PANC-1, H-125 and rat 3924A cells, for taxol the anti-proliferative IC50 was
      0.05, 0.06, 0.03 and 0.04 microM, respectively; for tiazofurin IC50 = 8.3, 2.3,
      1.8 and 6.9 microM. Thus, the concentrations for taxol required for IC50 for
      inhibiting cell proliferation were 166-, 38-, 60- and 173-fold lower than those
      for tiazofurin. Taxol and tiazofurin proved synergistic in all four cell lines
      tested. The synergism of taxol with tiazofurin should have implications in the
      clinical treatment of human solid tumors with particular relevance to ovarian,
      pancreatic, lung and hepatocellular carcinomas.

PMID- 8521380
TI  - Ataxia-telangiectasia and cellular responses to DNA damage.
AB  - Ataxia-telangiectasia (A-T) is a human disease characterized by high cancer risk,
      immune defects, radiation sensitivity, and genetic instability. Although A-T
      homozygotes are rare, the A-T gene may play a role in sporadic breast cancer and
      other common cancers. Abnormalities of DNA repair, genetic recombination,
      chromatin structure, and cell cycle checkpoint control have been proposed as the
      underlying defect in A-T; however, previous models cannot satisfactorily explain
      the pleiotropic A-T phenotype. Two recent observations help clarify the molecular
      pathology of A-T: (a) inappropriate p53-mediated apoptosis is the major cause of
      death in A-T cells irradiated in culture; and (b) ATM, the putative gene for A-T,
      has extensive homology to several cell cycle checkpoint genes from other
      organisms. Building on these new observations, a comprehensive model is presented
      in which the ATM gene plays a crucial role in a signal transduction network that
      activates multiple cellular functions in response to DNA damage. In this Damage
      Surveillance Network model, there is no intrinsic defect in the machinery of DNA
      repair in A-T homozygotes, but their lack of a functional ATM gene results in an
      inability to: (a) halt at multiple cell cycle checkpoints in response to DNA
      damage; (b) activate damage-inducible DNA repair; and (c) prevent the triggering
      of programmed cell death by spontaneous and induced DNA damage. Absence of damage
      sensitive cell cycle checkpoints and damage-induced repair disrupts immune gene
      rearrangements and leads to genetic instability and cancer. Triggering of
      apoptosis by otherwise nonlethal DNA damage is primarily responsible for the
      radiation sensitivity of A-T homozygotes and results in an ongoing loss of cells,
      leading to cerebellar ataxia and neurological deterioration, as well as thymic
      atrophy, lymphocytopenia, and a paucity of germ cells. Experimental evidence
      supporting the Damage Surveillance Network model is summarized, followed by a
      discussion of how defects in the ATM-dependent signal transduction network might
      account for the A-T phenotype and what insights this new understanding of A-T can
      offer regarding DNA damage response networks, genomic instability, and cancer.

PMID- 8521381
TI  - Comparative genomic in situ hybridization of colon carcinomas with replication
      error.
AB  - The aim of the present study was to detect complex genetic alterations in
      colorectal carcinomas with and without microsatellite instability (MIN) by
      comparative genomic in situ hybridization. MIN due to replication errors is the
      hallmark of hereditary nonpolyposis colon cancer. None of 6 MIN-positive tumors
      showed amplifications, and only 2 tumors displayed deletions of one chromosomal
      segment each. In contrast, different gains and losses were observed in 11 of 12
      MIN-negative carcinomas. The most frequent gains affected chromosomes 7, 13, and
      20q, whereas deletions were observed on chromosomes 17, 18, and 9p. These results
      demonstrate different mechanisms of genetic instability in subgroups of
      colorectal carcinomas and may, therefore, support the hypothesis of different
      etiologies in tumors with and without MIN.

PMID- 8521382
TI  - Immunohistochemical detection of the cyclin-dependent kinase inhibitor 2/multiple
      tumor suppressor gene 1 (CDKN2/MTS1) product p16INK4A in archival human solid
      tumors: correlation with retinoblastoma protein expression.
AB  - The retinoblastoma (RB) and cyclin-dependent kinase inhibitor 2/multiple tumor
      suppressor gene 1 (CDKN2/MTS1) tumor suppressor genes play important roles in the
      regulation of the cell cycle. The protein products of these two genes, pRB and
      p16INK4A ("p16"), respectively, inhibit progression from G1 to S phase. Moreover,
      p16 has been shown to exert its function through inhibition of CDK4-mediated
      phosphorylation of pRB. Both genes have been found to be mutated or deleted in a
      wide range of primary human tumors and tumor cell lines. However, the presence of
      CDKN2/MTS1 containing nonneoplastic elements in every tumor specimen may
      contribute to the apparent lower deletion detection rate in resected neoplasms
      compared to cell lines. We have developed an immunohistochemical assay that
      allows us to assess p16 expression in formalin-fixed, paraffin-embedded tissues.
      As controls, we used paraffin-embedded pellets of cell lines with well-defined
      p16 status (four positive and four negative lines), as well as routinely
      processed nude mouse xenografts of two p16-positive cell lines. p16-negative
      cells were characterized by the absence of nuclear staining, whereas cytoplasmic
      staining was variable. In neoplastic and normal tissues, the level of p16
      generally appeared to be low. We tested 75 random human malignancies from 4
      different anatomic sites for p16 expression and correlated the findings with the
      immunohistochemical presence or absence of pRB. Twenty % of tumors selectively
      lacked pRB, while 37% of neoplasms had undetectable p16. In 43% of all
      carcinomas, both pRB and p16 could be detected. Significant differences existed
      in the expression of both tumor suppressor genes between carcinomas from
      different sites. Breast cancers had the highest rate of p16 negativity (13 of
      20). Our data show that: (a) immunohistochemistry may be a suitable modality to
      screen for RB and CDKN2/MTS1 abnormalities in paraffin-embedded tissues; (b)
      undetectable levels of p16 expression occur at a relatively high frequency; (c)
      p16 and pRB expression in common human malignancies is not mutually exclusive;
      (d) loss of function of both tumor suppressor genes appears to be a distinctly
      uncommon phenomenon; and (e) different types of carcinomas have variable rates of
      disturbance in the p16/pRB pathway.

PMID- 8521383
TI  - Abrogation of p53-induced apoptosis by the hepatitis B virus X gene.
AB  - The p53 tumor suppressor gene product is a transcriptional transactivator and a
      potent apoptotic inducer. The fact that many of the DNA tumor virus oncoproteins
      bind to p53 and affect these p53 functions indicates that this interaction is an
      important step in oncogenic transformation. We and others have recently
      demonstrated that the hepatitis B virus oncoprotein, HBx, can form a complex with
      p53 and inhibit its DNA consensus sequence binding and transcriptional
      transactivator activity. Using a microinjection technique, we report here that
      HBx efficiently blocks p53-mediated apoptosis and describe the results of studies
      exploring two possible mechanisms of HBx action. First, inhibition of apoptosis
      may be a consequence of the failure of p53, in the presence of HBx, to upregulate
      genes, such as p21WAF1, Bax, or Fas, that are involved in the apoptotic pathway.
      Data consistent with this hypothesis include HBx reduction of p53-mediated
      p21WAF1 expression. Alternatively, HBx could affect p53 binding to the TFIIH
      transcription-nucleotide excision repair complex as HBx binds to the COOH
      terminus of p53 and inhibits its binding to XPB or XPD. Binding of p53 to these
      constituents of the core TFIIH is a process that may be involved in apoptosis.
      Because the HBx gene is frequently integrated into the genome of hepatocellular
      carcinoma cells, inhibition of p53-mediated apoptosis by HBx may provide a clonal
      selective advantage for hepatocytes expressing this integrated viral gene during
      the early stages of human liver carcinogenesis.

PMID- 8521384
TI  - O6-methylguanine DNA adduct formation and modulation by ethanol in placenta and
      fetal tissues after exposure of pregnant patas monkeys to N-nitrosodimethylamine.
AB  - Perinatal nitrosamine exposures may contribute to childhood cancer risk. To test
      primate fetal susceptibility to formation of cancer initiation-related DNA
      adducts from nitrosamines, pregnant patas monkeys were given 1.0 or 0.1 mg/kg N
      nitrosodimethylamine. Appreciable levels of the promutagenic O6-methylguanine
      adduct occurred in placental and fetal liver DNA after both doses and were lower
      but detectable in other fetal tissues after the higher dose. Coadministered
      ethanol (1.6 g/kg) reduced adducts in placenta and fetal liver by one-half and
      increased levels in other fetal tissues to the same degree. Thus, primate
      placenta and fetal tissues have a significant, ethanol-modulated capacity to
      activate N-nitrosodimethylamine, supporting implication of nitrosamines in human
      perinatal carcinogenesis and of alcohol as a modulating factor.

PMID- 8521385
TI  - Microtubule-active drugs taxol, vinblastine, and nocodazole increase the levels
      of transcriptionally active p53.
AB  - A range of DNA-damaging agents has been shown to increase cellular levels of the
      nuclear phosphoprotein p53 and to induce p53-dependent processes. We examined the
      ability of three microtubule-active agents, taxol, vinblastine, and nocodazole,
      to increase p53 levels and activate p53-dependent processes. When tested using a
      p53 DNA-binding assay, all three agents induced p53 in a dose-dependent manner.
      To varying degrees, these agents also induced p21WAF1/CIP1 mRNA and transcription
      in a chloramphenicol acetyl transferase reporter system. These data suggest there
      is an additional pathway for activating p53 and subsequent p53-dependent
      processes.

PMID- 8521386
TI  - Ischemia reperfusion injury in tumors: the role of oxygen radicals and nitric
      oxide.
AB  - Oxidative stress is a key process involved in the action of several therapeutic
      modalities used in cancer treatment. Ischemia reperfusion insult provides a model
      system for investigating the processes involved in determining the sensitivity of
      tumor tissue to oxidative stress. We have investigated the response of the murine
      CaNT tumor to ischemia reperfusion injury and the role that oxygen radicals and
      nitric oxide may play in this phenomenon. Our results show that little or no cell
      kill is detected in tumors exposed to up to 3 h of ischemia if the tumors are
      excised immediately before reperfusion. However, if reperfusion is permitted,
      then extensive cell kill is evident 24 h later. i.v. administration of superoxide
      dismutase or catalase, at the time when vascular reperfusion occurred, resulted
      in a significant protection against tumor cell kill, suggesting that the damage
      was mediated by oxygen radicals. Conversely, administration of an inhibitor of
      nitric oxide synthase, N omega-nitro-L-arginine, resulted in potentiation of
      tumor cell damage. Administration of a nitric oxide (NO) donor, diethylamine NO,
      at the time when vascular reperfusion occurred resulted in significant protection
      against tumor damage. These results suggest that nitric oxide is a potent
      mediator in determining tumor damage after ischemia reperfusion injury. The role
      of intrinsic NO production by murine tumors was investigated by measuring the
      accumulation of nitrate in the medium of tumor explants cultured in vitro in two
      tumors with differing sensitivity to ischemia reperfusion damage. The clamp
      insensitive tumor SaS showed a greater nitrate accumulation than the clamp
      sensitive tumor CaNT, which may confer a greater capacity for preventing tumor
      and endothelial cell damage after oxidative stress.

PMID- 8521387
TI  - Structural organization of the human folypoly-gamma-glutamate synthetase gene:
      evidence for a single genomic locus.
AB  - The cytotoxicity, and probably the selectivity, of folate antimetabolites depend
      upon the expression of the enzyme folylpoly-gamma-glutamate synthetase in tumor
      cells. Evidence for the existence of multiple forms of this enzyme and the need
      to define the control mechanisms determinant of expression levels in normal and
      neoplastic cells has focused attention on the gene(s) encoding these forms. The
      organization of the genomic locus for the human folylpoly-gamma-glutamate
      synthetase (FPGS) gene has been determined. The complete 2256 nucleotides of cDNA
      for the 5'-untranslated region, mitochondrial leader sequence, coding region, and
      3'-untranslated region were distributed on 15 exons stretching over 11.2 kb of
      genomic DNA. All of the restriction fragments found in diploid human genomic DNA
      could be accounted for by fragments contained on the isolated genomic clones.
      Likewise, Southern analysis of the transfected human genomic DNA that
      complemented the FPGS- phenotype of a hamster cell line indicated that the same
      gene had been integrated in all of three independently derived transfectants. We
      conclude that the genomic locus that we now report appears to be the only gene
      encoding FPGS-related sequences in the human complement.

PMID- 8521388
TI  - Lung cancer risk in African-Americans in relation to a race-specific CYP1A1
      polymorphism.
AB  - The possible association between lung cancer and a polymorphism of the CYP1A1
      gene specific to African-Americans was examined using peripheral blood DNA from
      144 incident cases of lung cancer and 230 population controls with detailed data
      on smoking and other risk factors for the disease. The CYP1A1 variant allele was
      present in 15.2% of controls and 16.7% of cases. The smoking-adjusted odds ratio
      for the presence of the variant allele in relation to lung cancer risk overall
      was 1.3 (95% confidence interval, 0.7-2.4). According to histological type, the
      strongest association was observed for squamous cell carcinoma (odds ratio, 2.1),
      but this result was compatible with chance (95% confidence interval, 0.8-5.9).
      Adenocarcinoma was not materially associated with the presence of the variant
      allele (odds ratio, 1.3; 95% confidence interval, 0.5-3.2). No important
      associations were observed upon stratification by several risk factors for lung
      cancer, including smoking history, occupational exposures to asbestos and motor
      vehicle exhaust, or low intake of the micronutrient antioxidants beta-carotene,
      vitamin E, or vitamin C. These results do not confirm an earlier report that this
      CYP1A1 polymorphism may be an important risk factor for adenocarcinoma of the
      lung in African-Americans.

PMID- 8521389
TI  - Description of a novel fusion transcript between HMGI-C, a gene encoding for a
      member of the high mobility group proteins, and the mitochondrial aldehyde
      dehydrogenase gene.
AB  - Aberrations involving the chromosomal region 12q24 are a nonrandom cytogenetic
      abnormality in frequent benign tumors mainly of mesenchymal origin, e.g., uterine
      leiomyomas, pleomorphic adenomas of the salivary gland, lipomas, or hamartomas of
      the lung. Mostly, these 12q24 abnormalities occur as a result of inversions also
      affecting chromosomal region 12q14-15. In addition to the frequent tumors
      mentioned above, these abnormalities have also been found in rare mesenchymal
      tumors, e.g., hemangiopericytomas. Although recently the molecular basis of the
      aberrations of chromosomal region 12q14-15, i.e., a rearrangement of the HMGI-C
      gene has been identified, the molecular roots of the 12q24 changes still remain
      to be elucidated. Herein we report on 3' rapid amplification of cDNA ends PCR
      results on cDNA from a primary uterine leiomyoma. As an ectopic sequence fused to
      exon 3 of the HMGI-C gene, we have identified a cDNA sequence that revealed 100%
      homology to exon 13 of the human mitochondrial aldehyde dehydrogenase gene (ALDH
      2). Because ALDH 2 maps to 12q24.1, this fusion transcript is a good candidate
      underlying the chromosomal rearrangements involving 12q24.

PMID- 8521390
TI  - Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of
      poor prognosis in non-small cell lung cancer.
AB  - Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is
      identical to the CD9 antigen. In previous studies, we showed that various types
      of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and
      diminished metastatic potential to the lung. More recently we used
      immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to
      demonstrate that the level of MRP-1/CD9 expression was inversely related to the
      clinical stage of a given carcinoma of the breast. In addition, we found that the
      primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than
      their respective metastatic lymph nodes. In consideration of these findings, we
      have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression
      in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage
      I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP
      1/CD9-positive tumors, and that gene expression was reduced in the tumors of the
      remaining 42 individuals. The overall rate of survival was strikingly higher
      among patients with positive tumors than in those whose tumors had reduced gene
      expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with
      adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis
      with the Cox regression model indicated that MRP-1/CD9 positivity correlated
      better with overall survival rate than did other variables, except lymph node
      status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may
      be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9
      may identify node-negative lung cancer patients and patients with adenocarcinomas
      who are at high risk for early disease recurrence.

PMID- 8521391
TI  - Mch3, a novel human apoptotic cysteine protease highly related to CPP32.
AB  - Recent evidence suggests that mammalian cysteine proteases related to
      Caenorhabditis elegans CED-3 are key components of mammalian programmed cell
      death or apoptosis. We have shown recently that the CPP32 and Mch2 alpha cysteine
      proteases cleave the apoptotic markers poly(ADP-ribose) polymerase (PARP) and
      lamins, respectively. Here we report the cloning of a new Ced-3/interleukin 1
      beta-converting enzyme-related gene, designated Mch3, that encodes a protein with
      the highest degree of homology to CPP32 compared to other family members. An
      alternatively spliced isoform, named Mch3 beta, was also identified. Bacterially
      expressed recombinant Mch3 has intrinsic autocatalytic/autoactivation activity.
      The specific activity of Mch3 alpha toward the peptide substrate DEVD-7-amino-4
      methylcoumarin and PARP resembles that of CPP32. Like interleukin 1 beta
      converting enzyme and CPP32, the active Mch3 alpha is made of two subunits
      derived from a precursor (proMch3 alpha). It was of interest that recombinant
      CPP32-p17 subunit can form an active heteromeric enzyme complex with recombinant
      Mch3 alpha-p12 subunit and vice versa, as determined by the ability of the
      heteromeric complexes to induce apoptosis in Sf9 cells. These data suggest that
      proMch3 alpha and proCPP32 can interact to form an active Mch3 alpha/CPP32
      heteromeric complex. We also provide evidence that CPP32 can efficiently cleave
      proMch3 alpha, but not the opposite, suggesting that Mch3 alpha activation in
      vivo may depend in part on CPP32 activity. The high degree of conservation in
      structure and specific activity and the coexistence of Mch3 alpha and CPP32 in
      the same cell suggests that the PARP cleavage activity observed during apoptosis
      cannot solely be attributed to CPP32 but could also be an activity of Mch3 alpha.

PMID- 8521392
TI  - Genomic organization of the ATM locus involved in ataxia-telangiectasia.
AB  - The ATM gene, involved in the genetic disorder ataxia-telangiectasia (AT), has
      been identified recently. This gene is suspected to predispose to malignancy and
      is located in a chromosomal region that we have recently found deleted in 50 to
      60% of breast and lung carcinomas. Because of its location and its function, the
      ATM gene is a strong candidate tumor suppressor or modifier gene of chromosome
      region 11q23. In this study, we define its genomic structure. The aim was to
      establish the basis for the development of mutation scanning methods based on DNA
      instead of RNA. We found that the gene spans a region of approximately 70-80 kb
      and is composed of 37 exons, ranging in size from 64 to 324 bp. Nucleotide
      sequences of all exon/intron boundaries were determined. With this information,
      it will be possible to develop simple genetic tests for the identification of
      homozygotes and heterozygotes, as well as determine whether the gene is involved
      in the pathogenesis of breast and other carcinomas.

PMID- 8521393
TI  - Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase
      activating kinase (CAK) assembly factor.
AB  - Mammalian CDK7 is a protein kinase identified as the catalytic subunit of cyclin
      dependent kinase (CDK)-activating kinase and as an essential component of the
      transcription factor TFIIH that is involved in transcription initiation and DNA
      repair. We have identified in human cells a number of CDK7-associated cellular
      proteins that appear to fall into two classes based on their relative [35S]
      metabolic labeling intensity. One class of proteins present in CDK7
      immunocomplexes as a minor fraction contains components of the TFIIH
      transcription complex such as p62 and p89ERCC3, whereas the other fraction
      contains four polypeptides (p35, p37Cyclin H, p75, and p95) that are
      stoichiometrically associated with CDK7. Whereas the levels of association of
      p35, p37Cyclin H, and p75 with CDK7 remain unchanged between density-arrested and
      proliferating Ewing sarcoma EW-1 cells, the association of p95 with CDK7 was
      significantly decreased as cells reached confluency. Through a large-scale
      immunopurification of CDK7 complexes and protein microsequencing, we have
      isolated a cDNA that encodes p35 and have shown that it is the human homologue of
      Mat1 that is involved in the assembly of CAK. MAT1 contains a highly conserved
      C3HC4 motif at its NH2 terminus, a characteristic feature shared among RING
      finger proteins. The human MAT1 gene expresses a single 1.6-kb transcript, the
      steady-state level of which, like CDK7 and cyclin H, varies significantly in
      different cell lines and in different terminally differentiated tissues.

PMID- 8521394
TI  - Microsatellite instability, mismatch repair deficiency, and genetic defects in
      human cancer cell lines.
AB  - The instability of short repetitive sequences in tumor DNA can result from
      defective repair of replication errors due to mutations in any of several genes
      required for mismatch repair. Understanding this repair pathway and how defects
      lead to cancer is being facilitated by genetic and biochemical studies of tumor
      cell lines. In the present study, we describe the mismatch repair status of
      extracts of 22 tumor cell lines derived from several tissue types. Ten were found
      to be defective in strand-specific mismatch repair, including cell lines from
      tumors of the colon, ovary, endometrium, and prostate. The repair defects were
      independent of whether the signal for strand specificity, a nick, was 5' or 3' to
      the mismatch. All 10 defective cell lines exhibited microsatellite instability.
      Repair activity was restored to 9 of these 10 extracts by adding a second
      defective extract made from cell lines having known mutations in either the hMSH2
      or hMLH1 genes. Subsequent analyses revealed mutations in hMSH2 (4 lines) and
      hMLH1 (5 lines) that could explain the observed microsatellite instability and
      repair defects. Overall, this study strengthens the correlation between
      microsatellite instability and defective mismatch repair and the suggestion that
      diminuition in mismatch repair activity is a step in carcinogenesis common to
      several types of cancer. It also provides an extensive panel of repair-proficient
      and repair-deficient cell lines for future studies of mismatch repair.

PMID- 8521395
TI  - Tumor suppressor loci on mouse chromosomes 9 and 16 are lost at distinct stages
      of tumorigenesis in a transgenic model of islet cell carcinoma.
AB  - Techniques that detect loss of genetic heterozygosity (LOH) have helped elucidate
      genes involved in human cancers. Previously, a genome-wide search using simple
      sequence length polymorphisms to detect LOH in islet cell tumors arising in a
      transgenic mouse model of multistage tumorigenesis had revealed two candidate
      tumor suppressor genes, Loh1 and Loh2, on chromosomes 9 and 16, respectively. We
      now have analyzed the early stages of tumor development in this model
      (hyperplastic, early angiogenic, and angiogenic islets) for LOH involving regions
      of chromosomes 9 and 16. On chromosome 9, hyperplastic and early angiogenic
      islets reveal a low rate of loss (< 5%) indistinguishable from background;
      angiogenic islets showed a 9% rate, whereas the final tumor stage had an 18%
      rate. By contrast, LOH was observed much earlier on chromosome 16. Notably, the
      LOH rate in angiogenic islets was 29%, comparable to the rate seen in end-stage
      tumors (32%). The results show that the two loci are lost preferentially at
      different stages of tumorigenesis. The observation that a high LOH rate at Loh2
      is seen in the angiogenic islet stage suggests that this locus may contain an
      angiogenesis suppressor; in contrast, the later appearance of Loh1 may contribute
      to the progression from the angiogenic stage to a solid tumor. Tumors containing
      chromosomes with partial LOH have allowed improved localization of Loh1 to a
      region of approximately 3.2 centiMorgans on chromosome 9, syntenic with human
      chromosomes 3q and 15q.

PMID- 8521396
TI  - Volume-sensitive chloride channels associated with human cervical carcinogenesis.
AB  - Previous controversy has risen from the purported equivalence of the volume
      sensitive chloride channels with P-glycoprotein. The aim of this study was to
      investigate the association between expression of volume-sensitive Cl- channels
      and the process of malignant transformation of cervical epithelial cells. We
      studied the activations of volume-sensitive and cAMP-mediated chloride currents
      in various human cervical squamous cells that were representative of different
      stages of cervical carcinogenesis, i.e., normal cervical epithelium, low-grade
      cervical intraepithelial neoplasia, carcinoma in situ, and invasive carcinoma
      using the whole-cell patch clamp technique. The volume-sensitive chloride
      channels, however, were significantly activated only in the four cervical cancer
      cell lines, primary culture cells of carcinoma in situ, and invasive cancer of
      the cervix. The expression of volume-sensitive chloride currents was independent
      of the state of human papillomavirus positivity. When these cells were exposed to
      hypotonic shock, the cells swelled, and outward rectified chloride currents were
      observed. These effects were readily reversed by returning the cells to isotonic
      medium. In addition, 4,4'-diisothiocyanatostilbene-2,2-disulfonic acid, 1,9
      dideoxyforskolin, and verapamil reversibly abolished the volume-sensitive Cl-
      currents. In contrast, none of the cells from normal cervices and human
      papillomavirus-immortalized cell lines, the in vitro equivalent of low-grade
      cervical intraepithelial neoplasia, developed substantial chloride currents on
      exposure to hypotonicity. cAMP-mediated chloride currents were ubiquitously
      activated in all cervical squamous cells, regardless of the stages of
      carcinogenesis. This is the first report suggesting an in vivo association
      between the development of volume-sensitive chloride currents and human
      carcinogenesis.

PMID- 8521397
TI  - Mutant p53 but not hepatitis B virus X protein is present in hepatitis B virus
      related human hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) X protein is thought to play an important role in the
      development of hepatocellular carcinoma. Recent studies on a transgenic mouse
      tumor model suggest that HBV X protein may contribute to transformation by
      binding to and inactivating the cellular growth suppressor protein p53. We have
      studied 31 hepatocellular carcinoma tissues from Chinese patients for the
      possible occurrence of such interactions. Although most of the samples contained
      markers of HBV infection, including free and/or integrated HBV DNA, there was no
      detectable expression of HBV X protein by Western blot, immunoprecipitation, or
      histochemical staining. There was also no evidence of HBV X protein associated
      with p53 immunoprecipitated from the tumors. These observations suggest that, in
      naturally occurring human hepatocellular carcinoma, such interactions are
      uncommon and, therefore, unlikely to be of relevance in the latter stages of
      tumor development. On the other hand, 29 of 31 (93%) samples contained mutated
      forms of p53, as determined by various antibodies that detect wild-type or mutant
      p53 or both, and by the association of heat shock protein 70 with
      immunoprecipitated p53. These results show that conformationally altered p53
      protein is present in tumors at a much higher frequency than is suggested by the
      presence of known mutations in the gene. This mutant p53 is functionally
      inactive, as suggested by the lack of expression of the p53-induced M(r) 21,000
      Cip1/Waf1 protein in the tumors. Because this inactivation of p53 was not
      correlated with the expression of HBV X protein, any interaction of HBV X protein
      with p53 may be relevant only during acute infection. Such an interaction could
      serve to relax cell growth control at a time when virus replication requires
      hepatocyte destruction to be balanced by regeneration.

PMID- 8521398
TI  - Mutation screening in the hMLH1 gene in Swedish hereditary nonpolyposis colon
      cancer families.
AB  - Hereditary nonpolyposis colorectal cancer is caused by heritable defects in the
      DNA mismatch repair genes hMLH1, hMSH2, hPMS1, and hPMS2. We have used denaturing
      gradient gel electrophoresis to analyze the 19 exons and exon-intron borders of
      hMLH1 in 39 Swedish hereditary nonpolyposis colorectal cancer families. Germline
      mutations were found in eight of these families: two splice mutations affecting
      exons 3 and 7, respectively, and six missense mutations, of which, four were in
      exon 2 and one each were in exons 1 and 16. The relatively high number of
      missense mutations raises several important clinical and technical issues. Such
      alterations can be identified only when using methods that target DNA or mRNA
      sequence alteration because they do not cause protein truncations detected by in
      vitro translation assays. Furthermore, the relationship between these missense
      mutations and the predisposition to colon cancer is difficult to determine
      without additional information; thus, genetic counseling based on mutation data
      is difficult.

PMID- 8521399
TI  - Differential cellular and subcellular expression of the human multifunctional
      apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme.
AB  - The multifunctional mammalian apurinic/apyrimidinic endonuclease (APE) is
      responsible for the repair of apurinic/apyrimidinic sites in DNA. In addition,
      this enzyme has been shown to function as a redox factor facilitating the DNA
      binding capability of JUN and FOS, as well as numerous other transcription
      factors through the alteration of the transcription factor redox state.
      Biochemical studies of organ homogenates have shown that APE is present in the
      different tissues studied at similar concentrations. The present study examines
      the immunohistochemical distribution of APE in several organs and demonstrates
      new and unexpected patterns of cellular and subcellular localization of this
      enzyme. In the hippocampus, the APE protein was highly expressed in neurons of
      the dentate gyrus and regions CA3 and CA4, and unexpectedly, the staining was
      primarily cytoplasmic. AP endonuclease immunoreactivity in the cerebellum was
      found in the granule and Purkinje cells, both cytoplasmic and nuclear. APE
      staining of the hypoglossal nucleus of the brainstem, where motor neurons that
      control tongue movement reside, showed reactivity in the cytoplasmic Nissl
      substance. Skin, liver, and duodenum demonstrated nuclear staining; however, in
      the duodenum, only the enterocyte nuclei of the proximal villus and the crypts of
      Lieberkuhn were stained, with no staining of the distal villus. These results
      suggest that APE has different regulatory and functional roles in different cells
      and organs of the body. This study shows the importance of correlating in vitro
      findings in tissue culture cells with the organism as a whole. The cytoplasmic
      staining seen in parts of the brain and in liver suggests that there may be
      additional functions for the APE yet to be described.

PMID- 8521400
TI  - Prognostic significance of cell kinetics in laryngeal squamous cell carcinoma:
      clinicopathological associations.
AB  - A consecutive series of 99 untreated patients undergoing radical surgical
      resection for stage I-IV laryngeal carcinomas has been studied prospectively. Our
      purpose was to analyze the predictive relevance of proliferative variables
      studied [proliferating cell nuclear antigen (PCNA) expression, volume-corrected
      mitotic (M/V) index, and S-phase fraction (SPF)] on clinical outcome in relation
      to DNA ploidy and clinicopathological features. All of the patients were followed
      up for a median of 32 months (range, 5-58 months). A weak, but significant,
      positive correlation was found between M/V and PCNA indices (except the PCNA
      weighted mean index:labeling index ratio) or these indices and SPF. At univariate
      analysis, node positivity (P < 0.05), poor histological grade (P < 0.01), DNA
      aneuploidy (P < 0.01), a high SPF (P < 0.01), and a high M/V index (P < 0.05)
      proved to be related significantly to quicker relapse, whereas T4 (P < 0.05),
      subglottic site (P < 0.05), DNA aneuploidy (P < 0.01) and a high SPF (P < 0.01)
      were related significantly to shorter overall survival. With multivariate
      analysis, a high SPF (> 12.1%) and histological grade (G3) were related to the
      risk of relapse (relative risk, 8.65 and 5.45, respectively), whereas only a high
      SPF was related independently to the risk of death (relative risk, 7.30). Our
      study has identified SPF, in addition to histological grade, as an important
      biological indicator in laryngeal carcinomas.

PMID- 8521401
TI  - DNA topoisomerase II alpha expression is associated with alkylating agent
      resistance.
AB  - Increased expression of DNA topoisomerase II alpha has been associated with
      resistance to certain DNA-damaging alkylating agents, but no causal relationship
      or mechanism has been established. To investigate this observation, we developed
      a model of topoisomerase II overexpression by transfecting a full-length Chinese
      hamster ovary topoisomerase II alpha into EMT6 mouse mammary carcinoma.
      Topoisomerase II alpha-transfected cell lines demonstrated continued
      topoisomerase II alpha mRNA and protein expression, which were undetectable in
      vector-only lines, in stationary phase (G0-G1). The topoisomerase II
      transfectants were approximately 5-10-fold resistant to the alkylating agents
      cisplatin and mechlorethamine. Upon release from G0-G1, the topoisomerase II
      transfectants demonstrated more rapid thymidine incorporation and shorter cell
      doubling times than control cells. Purified topoisomerase II and nuclear extracts
      with topoisomerase II-decatenating activity bound to cisplatin-treated DNA with
      significantly greater affinity than to untreated DNA in a cisplatin concentration
      dependent manner. These observations suggest that expression of topoisomerase II
      alpha may have a role in cellular resistance to antineoplastic alkylating agents.
      The mechanism for this may involve increased binding of topoisomerase II alpha to
      alkylating agent-damaged DNA.

PMID- 8521402
TI  - Enhanced antitumor activity for the thymidylate synthase inhibitor 1843U89
      through decreased host toxicity with oral folic acid.
AB  - The purpose of this investigation was to determine whether antitumor selectivity
      of the third generation thymidylate synthase inhibitor 1843U89 could be enhanced
      by a combination of the drug with folic acid. The effects of folic acid on
      toxicity of 1843U89 to the dog and mouse and on antitumor efficacy of 1843U89 in
      the mouse were studied. These data were compared to the effect of folic acid on
      the in vitro cell culture antitumor activity of 1843U89. The sensitivity of eight
      cancer cell lines (three ovarian, one colon, one ileocecal, one epidermoid, one
      osteosarcoma, and one breast line) to 1843U89 was tested in vitro in the presence
      and absence of folic acid. Folic acid concentrations greater than 100 microM were
      required to decrease 1843U89 activity in seven of the cell lines. Only the
      activity in HCT-8, the ileocecal line, was reserved at folic acid concentrations
      below 100 microM. Oral folic acid given 30 min prior to an i.v. dose of 1843U89
      increased the maximally tolerated dose and the lethal dose of 1843U89, both in
      dogs and in thymidine-depleted mice. In mice, oral folic acid produced little or
      no effect upon the antitumor efficacy of 1843U89 in two of three tumor cell lines
      in vivo. HCT-8, the line that was sensitive to folate reversal in vitro, was also
      sensitive in vivo. The results show that an oral dose of folic acid 30 min prior
      to i.v. 1843U89 can block mouse and dog intestinal toxicity without decreasing
      efficacy of 1843U89 in two of three human tumor lines in the nude mouse. Thus,
      the data reported here indicate that the antitumor selectivity of 1843U89 may be
      enhanced through a combination of 1843U89 with oral folic acid.

PMID- 8521403
TI  - Imaging the expression of transfected genes in vivo.
AB  - Imaging the expression of successful gene transduction has been demonstrated in
      vivo for the first time by using an appropriate combination of "marker gene" and
      "marker substrate" in an experimental animal model. The herpes simplex virus 1
      thymidine kinase (HSV1-tk) gene was selected as an example of a marker gene, and
      the recombinant STK retrovirus containing HSV1-tk was used to transduce RG2
      glioma cells in vitro and in vivo. RG2TK+ cell lines expressing the HSV1-tk gene
      and three potential marker substrates for the HSV1-TK enzyme were evaluated.
      Radiolabeled 5-iodo-2'-fluoro-2'deoxy-1-beta-D-arabinofuranosyluracil (FIAU) was
      shown to be a substantially better marker substrate for the HSV1-TK enzyme than 5
      iodo-2'-deoxyuridine or ganciclovir. The magnitude of FIAU accumulation in
      different RG2TK+ clones corresponded to their sensitivity to ganciclovir and to
      the level of HSV1-tk mRNA expression. Imaging the expression of HSV1-tk in
      transduced RG2 tumor cells was demonstrated in animals using quantitative
      autoradiography; 2-[14C]FIAU accumulation was shown to be high in RG2TK+ brain
      tumors growing in one hemisphere and very low in nontransduced RG2 tumors in the
      contralateral hemisphere. Transduction of RG2 tumor cells with the HSV-tk gene in
      vivo resulted in tumors which accumulated FIAU to high levels and produced
      clearly defined images. Given the level of FIAU accumulation in the transduced
      tumors, it is likely that a clinically applicable method for imaging HSV1-tk gene
      expression can be implemented using existing clinical imaging techniques.

PMID- 8521404
TI  - Host CD4+ T lymphocytes are required for the synergistic action of interferon
      alpha/beta and adoptively transferred immune cells in the inhibition of visceral
      ESb metastases.
AB  - Effective adoptive immunotherapy of immunocompetent DBA/2 mice challenged i.v.
      with the highly metastatic ESb T-cell lymphoma required the combined treatment of
      recipient mice with tumor-sensitized spleen cells and IFN-alpha/beta. In
      contrast, immune spleen cells and IFN-alpha/beta treatment did not increase the
      survival time of ESb-injected DBA/2-nu/nu mice, DBA/2-bg/bg mice, or normal DBA/2
      mice injected with antibody to CD4. Treatment of immunocompetent DBA/2 mice with
      antibody to asialo-GM1, silica, dichloromethylene diphosphonate-containing
      liposomes, or 500 rads whole-body gamma-irradiation did not diminish the
      antimetastatic action of ESb-immune cells and IFN-alpha/beta. These results
      indicate that adoptively transferred immune T lymphocytes and IFN-alpha/beta act
      together with host CD4+ T lymphocytes/factors to inhibit ESb visceral metastases.
      Combined treatment with ESb-immune cells together with interleukin-1 beta (IL-1
      beta), IL-2, tumor necrosis factor-alpha, or granulocyte-macrophage colony
      stimulating factor did not increase the survival time of normal DBA/2 mice
      challenged with ESb cells. In contrast, IL-12, which had only a slight
      antimetastatic effect when administered alone, did synergize with ESb-immune
      spleen cells and increased the survival time of ESb-challenged mice to a similar
      extent as did IFN-alpha/beta and immune spleen cells. Treatment of DBA/2 mice
      with potent antibody to IFN-alpha/beta did not abrogate the capacity of IL-12 and
      ESb-immune spleen cells to inhibit ESb metastases. Unlike immunotherapy with ESb
      immune cells and IFN-alpha/beta, ESb-immune cells together with IL-12 inhibited
      ESb metastases in immunodeficient DBA/2-bg/bg mice.

PMID- 8521405
TI  - Analysis of the T cell receptor in the lymphoproliferative disease of granular
      lymphocytes: superantigen activation of clonal CD3+ granular lymphocytes.
AB  - To investigate whether cell populations in CD3+ lymphoproliferative disease of
      granular lymphocytes (LDGLs) were skewed toward the use of specific V beta
      regions, we studied the repertoire of T-cell receptor (TCR) V beta gene products
      in 18 patients, as well as their relationship to the clonal bands in the Southern
      blot and the activation mediated by superantigens. Using a panel of monoclonal
      antibodies (mAbs) for conserved V beta segments and PCR, a dominant population
      expressing a specific V beta region was demonstrated in all patients. In five
      (27%) cases, granular lymphocytes (GLs) were found to express the V beta 13.1,
      while V beta 8 and V beta 6 were each expressed in three (17%) cases. The
      remaining cases were characterized by the proliferation of TCR V beta 2, V beta
      3, V beta 4, V beta 9, V beta 12, V beta 16, and V beta 20. This finding
      indicates a biased usage of a limited TCR V beta in LDGLs, since nearly 60% of
      the cases utilized only three families of the TCR V beta genes. In all of the
      cases studied, we proved that the subset recognized by mAb and PCR was identical
      to that accounting for the extra band(s) of the Southern blot. This finding
      confirms the clonal nature of the population identified according to TCR V beta
      expression both by phenotype and PCR. On functional grounds, we evaluated whether
      GLs can be activated through the specific TCR using the superantigens recognizing
      discrete V beta families, such as staphylococcal proteins, including SEA, SEB,
      SEC1, SEC2, SED, and SEE. We demonstrated that the TCR-alpha/beta of clonal GLs
      in LDGL patients is functionally active in delivering cytotoxic and proliferative
      signals upon superantigen activation.

PMID- 8521406
TI  - The involvement of transforming growth factor beta in the impaired antitumor T
      cell response at the gut-associated lymphoid tissue (GALT).
AB  - We studied the antitumor immune response in gut-associated lymphoid tissue
      (GALT), which is the tolerance-inducing site for numerous dietary antigens. The
      mice inoculated with colon 26 carcinoma (C-26) into the subserosal space of the
      cecum (i.c.) showed a more rapid tumor growth than did the mice inoculated s.c.
      with C-26 into the flank. In addition, the serum of the i.c. C-26-inoculated mice
      showed a more potent suppressive activity, and their plasma contained a higher
      level of transforming growth factor than the s.c. C-26-inoculated mice. We also
      evaluated the tumor-specific T-cell response in the GALT by utilizing B7
      transfected P815 mastocytoma (B7/P815). The rejection of i.c. inoculated B7/P815
      was delayed compared to that of the s.c. inoculated B7/P815. The draining
      axillary lymph node (LN) cells of the s.c. B7/P815-inoculated mice exhibited a
      CD4+ T-cell-dependent proliferative response to in vitro restimulation, whereas
      the draining mesenteric LN cells of the i.c. B7/P815-inoculated mice exhibited no
      apparent response even with the addition of interleukin 2. However, such draining
      mesenteric LN cells did produce higher levels of interleukin 2 and transforming
      growth factor beta than the draining axillary LN without any stimulation, and
      their production of such cytokines depend on the CD4+ and CD8+ cells,
      respectively. Collectively, our results suggest the possibility that the impaired
      antitumor T-cell response in the GALT may be attributed to "bystander
      suppression" by TGF-beta-producing CD8+ T cells.

PMID- 8521407
TI  - Overexpression of the XPA repair gene increases resistance to ultraviolet
      radiation in human cells by selective repair of DNA damage.
AB  - Overexpression of XPA genes, both wild type and a missense mutant, which code for
      a damage-specific, DNA-binding protein, increased the survival of repair
      deficient and -competent human cells to levels above that of normal cells that
      did not overexpress XPA. The first 3 h after cells were damaged were most
      critical to achieving this increased survival. The dose at which 37% of the
      irradiated population survives could be restored to about one-half that of normal
      cells, with no detectable genome-wide repair of pyrimidine dimers or (6-4)
      photoproducts, suggesting that intermediate levels of XPA gene expression can
      direct repair to restricted critical regions of the genome. Current views of
      repair implicate transcriptionally active genes as a major component of such
      critical regions. Consistent with this interpretation, the repair of a
      transfected, actively expressed luciferase gene was higher than that of genomic
      DNA at intermediate and higher levels of XPA expression. High levels of XPA
      expression resulted in increased repair at early times after irradiation and
      extensive repair of (6-4) photoproducts but little, if any, pyrimidine dimer
      repair in the whole genome. At the highest level of expression, some clonal cell
      lines acquired resistance to radiation that corresponded to a dose at which 37%
      of the irradiated population survives that was about 1.5 to 2 times that of
      normal cells. The XPA gene product, therefore, can influence levels of DNA repair
      and radiation sensitivity quantitatively by contributing to selective repair at
      certain sites in the genome.

PMID- 8521408
TI  - Wild-type p53 and v-Src exert opposing influences on human vascular endothelial
      growth factor gene expression.
AB  - Angiogenesis, the development of new capillaries, is tightly controlled by the
      balance of positive and negative regulatory pathways. A newly described
      angiogenic factor, vascular endothelial growth factor/vascular permeability
      factor (VEGF/VPF), binds exclusively to endothelial cells and promotes their
      proliferation. Here we have studied the role of p53, a tumor suppressor, and v
      Src, an oncogene on VEGF regulation. Wild-type p53 down-regulated endogenous VEGF
      mRNA level, as well as VEGF promoter activity, in a dose-dependent manner,
      whereas mutant forms of p53 had no effect. Overexpression of v-Src, known to up
      regulate VEGF expression, activated a VEGF promoter-luciferase construct in a
      dose-dependent manner. Moreover, v-Src, in the presence of wt-p53, was unable to
      activate transcription of the VEGF promoter. Collectively, these data suggest
      that wild-type p53 may play a role in suppressing angiogenesis.

PMID- 8521409
TI  - Interleukin-1 beta-converting enzyme mediates cisplatin-induced apoptosis in
      malignant glioma cells.
AB  - Increasing the susceptibility of tumor cells to apoptotic cell death following
      chemotherapy is of importance to the outcome of cancer treatment. Although the
      tumor suppressor gene p53 is required for efficient induction of apoptosis by
      chemotherapeutic agents, it is not the only apoptosis mediator gene. The
      molecular mechanisms mediating apoptosis following chemotherapy via p53-dependent
      or p53-independent pathways remain unclear. We show here that cis
      diamminedichloroplatinum (cisplatin) induces the expression of interleukin-1 beta
      converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell
      death gene ced-3, in murine and human malignant glioma cells during apoptosis
      regardless of their p53 status. Furthermore, overexpression of the murine ICE
      gene induces apoptosis in these tumor cells. The apoptosis induced by cisplatin
      treatment or murine ICE overexpression can be suppressed by the tetrapeptide ICE
      inhibitor Ac-YVAD-CMK or the apoptosis inhibitors bcl-2 or bcl-2-related bcl-XL
      gene. These findings suggest that ICE may mediate apoptosis induced by
      chemotherapy, and its induction could represent a novel approach for the
      effective treatment of malignant glioma.

PMID- 8521410
TI  - Genetic analysis of benign, low-grade, and high-grade ovarian tumors.
AB  - Genetic abnormalities were assessed in 56 benign, low-, and high-grade ovarian
      tumors using comparative genomic hybridization (CGH) and analysis of loss of
      heterozygosity (LOH). In addition, 95 epithelial tumors were analyzed for
      microsatellite repeat instability. DNA sequence copy number abnormalities (CNAs)
      were not detected in the benign tumors, and more were detected in high-grade than
      in low-grade cancers. Almost no microsatellite repeat instability was detected in
      these cancers. CNAs occurring in more than 30% of the cancers included increased
      copy number on 3q25-26 and 8q24 and reduced copy number on 16q and 17pter-q21.
      Another 14 CNAs occurred in more than 20% of the cancers. Increased copy number
      at 3q25-26 and 20q13 was the most frequent CNA in low-grade tumors, and increased
      copy number at 8q24 occurred preferentially in high-grade tumors. The presence of
      a large number of CNAs per tumor was significantly correlated with reduced
      patient survival duration. Reduced copy number on 17pter-q21 was most strongly
      associated with accumulation of a large number of CNAs. The overall concordance
      between LOH and reduced copy number detected by CGH was 84%, but only 31% of the
      LOH was associated with reduced copy number detected using CGH.

PMID- 8521411
TI  - Regulation of transforming growth factor beta receptors in H-ras oncogene
      transformed rat intestinal epithelial cells.
AB  - We have reported that over expression of the H-ras oncogene causes resistance to
      growth inhibition by transforming growth factor beta 1 (TGF-beta 1) and a time
      dependant switch of type II to type I TGF-beta receptor expression in the rat
      intestinal epithelial cell line IEC-18 (J. Filmus, J. Zhao, and R. N. Buick,
      Oncogene, 7: 521-526, 1992). Here, we investigate the possible mechanisms
      involved in H-ras-mediated regulation of TGF-beta receptors in an IEC-18 cell
      clone expressing H-ras, conditional on the activity of a dexamethasone-sensitive
      promoter. The switch from type II to type I receptor expression in response to H
      ras expression has a requirement for de novo RNA synthesis. In addition,
      accumulation of TGF-beta receptor type II mRNA is approximately 5-fold lower in
      ras-expressing cells compared to control cells. Nuclear run-on experiments
      suggest that the down-regulation of type II receptor mRNA by H-ras oncogene is
      based, at least in part, on reduced transcription. We have also analyzed the
      consequences of H-ras expression on the properties of the TGF-beta receptors.
      Type I and II in IEC-18 cells and type I receptors in ras-transformed cells have
      similar characteristics in terms of binding affinities for TGF-beta 1 (or TGF
      beta 2) turnover rates and glycosylation states. Notably, the type I receptors in
      ras-transformed cells are not capable of ligand-induced internalization. Although
      H-ras expression in IEC-18 cells causes resistance to TGF-beta-mediated growth
      inhibition, the cells remain responsive to TGF-beta 1 stimulation of fibronectin
      expression. These results are discussed in the context of the knowledge of TGF
      beta receptor complexity and signal transduction, and with reference to the
      potential role for loss of TGF-beta-mediated negative growth regulation in
      malignant transformation.

PMID- 8521412
TI  - Genomic alterations and instabilities in renal cell carcinomas and their
      relationship to tumor pathology.
AB  - A comprehensive genome scan for loss of heterozygosity (LOH) in 33 renal cell
      carcinomas indicates that mutations of tumor suppressor genes on several
      different chromosomes are required for malignant transformation in this disease.
      In the case of nonpapillary renal carcinomas chromosomes 3p, 6q, 8p, 9pq, and 14q
      exhibit elevated levels of LOH. Although 3p is the most frequently lost
      chromosome arm, in no case is 3p observed as the sole allelic loss because it
      always occurs in conjunction with the loss of either 6q, 8p, or 14q. This result
      indicates that the mutation of a tumor suppressor gene on 3p, most likely von
      Hippel-Lindau disease (VHL), may be necessary but is not sufficient for the
      development of nonpapillary renal cell carcinoma. In papillary renal tumors, LOH
      is observed most often for chromosomes 6pq, 9p, 11q, 14q, and 21q. This suggests
      that tumor suppressor genes located on chromosomes 6q, 9pq, and 14q may be
      involved in the development and/or progression of both nonpapillary and papillary
      renal cell carcinomas. However, LOH in papillary tumors appears to be especially
      elevated for 11q and 21q and reduced for 3p and 8p indicating that there are also
      tumor suppressor genes specific to each form of the disease. There is no
      correlation between stage of disease and the extent of LOH, loss of a particular
      chromosome, or the number of chromosomes that show allele imbalance. Early and
      late stage tumors may exhibit either extensive LOH or no apparent allele loss;
      similarly, allelic imbalances are observed in both early and late stage renal
      cell carcinomas. This suggests that a gene (or genes) regulating mitotic
      chromosome stability may be mutated in some renal tumors. Preliminary evidence
      points to an association between genome instability and LOH of 14q. Finally, a
      distinct type of microsatellite instability has been detected in 21% of renal
      cell carcinomas and occurs at a frequency of 4.4 x 10(-4)/locus. The most common
      mutation is a 2-bp insertion in a CA repeat. This alteration is not restricted to
      a particular histopathology or clinical stage, and it is not associated with
      allelic loss of a specific chromosome. The frequency of this event is similar to
      that which occurs spontaneously in germline microsatellite loci and is probably
      not the result of a defect in a mismatch repair gene. It is possible that this
      type of microsatellite instability is general and may occur in most, if not all,
      carcinomas.

PMID- 8521413
TI  - c-fos is not essential for v-abl-induced lymphomagenesis.
AB  - Recent studies have suggested that cellular transformation by abl oncoproteins
      may be mediated by the ras signaling pathway. One of the main nuclear targets of
      this signal transduction cascade is the Fos and Jun family of transcription
      factors. To test the relevance of the c-fos proto-oncogene for v-abl-induced
      cancer development, we inoculated c-fos-deficient mice with the Abelson murine
      leukemia virus. Neonatal c-fos-deficient mice infected with the Abelson complex
      are able to develop the pre-B-cell lymphoma that characterizes Abelson disease. c
      fos-deficient animals succumb to the disease with similar kinetics as their wild
      type and heterozygous littermates. Moreover, the transformed cell that brings
      about the malignancy in mutant mice is the same pre-B-cell lymphoblast that is
      seen in control animals. These results demonstrate that c-fos is not required for
      in vivo transformation by v-abl.

PMID- 8521414
TI  - Multiple mechanisms of p16INK4A inactivation in non-small cell lung cancer cell
      lines.
AB  - p16INK4A, a specific inhibitor of cyclin-dependent kinase (cdk)4 and cdk6, is a
      candidate tumor suppressor in malignancies with wild-type retinoblastoma (Rb).
      Loss of p16INK4A frees these cdks from inhibition, permitting constitutive
      phosphorylation of Rb and inactivation of its growth suppressive properties.
      Consistent with this model, Rb-positive non-small cell lung cancers (NSCLCs) have
      little or no detectable p16INK4A protein, whereas Rb-negative lung cancers have
      abundant p16INK4A. However, only some NSCLCs have homozygous deletions or
      nonsense mutations in a remaining p16INK4A allele, suggesting that other
      mechanisms must account for absent or low levels of p16INK4A protein. Here, we
      analyzed 9 Rb-positive NSCLC cell lines for the controls governing p16INK4A
      activity. Four lines had homozygous deletions of p16INK4A (SK-LU-1, SK-MES-1, A
      427, and SW900), and three had a point mutation in a single allele. First, in
      H520 cells, the previously reported deletion at codon 45 results in a frameshift
      that produces no detectable protein. Second, in Calu-3 cells, a His to Tyr
      substitution at codon 83 produced a variant with a shortened half-life that was
      unable to form complexes with cdk4 or cdk6. Third, in H661 cells, the previously
      reported point mutation in the second intron splice donor site resulted in a
      smaller p16INK4A protein. Although this variant formed complexes with cdk4 and
      cdk6, it had a profoundly reduced half-life, producing low steady-state levels of
      p16INK4A and abundant levels of free cdks. Finally, Calu-1 and Calu-6 cells
      transcribed no detectable mRNA encoding authentic p16INK4A. These cell lines
      displayed methylation of the CpG island surrounding the first exon of p16INK4A
      and expressed abundant levels of a nontranslated mRNA containing an alternative
      first exon (E1 beta), as did all other cell lines in which the p16INK4A locus was
      not deleted. These data indicate that Rb-positive NSCLC cells have evolved a
      variety of pathways to suppress p16INK4A expression. Reintroduction of p16INK4A
      into these cell lines by retroviral transfer resulted in a reduced growth rate,
      increased abundance of hypophosphorylated Rb, accumulation of cells in G1, and a
      less transformed morphology in Rb-positive, but not Rb-negative cells, suggesting
      that loss of p16INK4A is essential for maintenance of the transformed phenotype.

PMID- 8521415
TI  - Superoxide dismutase in SAS human tongue carcinoma cell line is a factor defining
      invasiveness and cell motility.
AB  - This article describes an apparent inverse relationship between cell motility and
      intracellular Cu-Zn superoxide dismutase (SOD) activity of two human squamous
      carcinoma-derived clones, SAS-H1 with high invasiveness and SAS-L1 with low
      invasiveness. Clone SAS-H1 exhibited significantly greater motility than SAS-L1
      but had significantly lower levels of intracellular Cu-ZnSOD than SAS-L1 cells.
      We then transfected Cu-ZnSOD antisense cDNA into SAS-L1 to reduce the
      intracellular Cu-ZnSOD activity. Antisense cDNA transfected SAS-L-AS clones had
      lower Cu-ZnSOD activity than control vector-transfected SAS-L-Neo clones, and
      this was associated with increased motility. Invasiveness of SAS-H1 and SAS-L-AS1
      was enhanced by superoxide treatment, while the invasiveness of SAS-L1 was
      unaffected. These findings indicate that intracellular SOD is involved in cell
      motility by virtue of its action in scavenging superoxide in the cells.

PMID- 8521416
TI  - Loss of the tumorigenic phenotype with in vitro, but not in vivo, passaging of a
      novel series of human bronchial epithelial cell lines: possible role of an alpha
      5/beta 1-integrin-fibronectin interaction.
AB  - We established an immortalized, nontumorigenic human bronchial epithelial cell
      line by transfection with the origin of replication-defective SV40 large T
      plasmid. This line spontaneously became tumorigenic at passage 184 (NL20T),
      although subsequent passages (passages 189, 200, and 205) failed to form tumors.
      The tumorigenic cell line NL20T was reinoculated back into athymic nude mice, and
      the two subsequently derived cell lines (NL20T-A and NL20T-B) have been passaged
      85 times in vitro and remain tumorigenic. However, late-passage NL20T cells
      consistently lose their tumorigenicity when passaged in vitro on tissue culture
      plastic dishes (NL20T-n cells). Thus, two of the cell lines, NL20 and NL20T,
      reverted to the nontumorigenic phenotype reproducibly and spontaneously following
      serial passage on plastic tissue culture plates, whereas cells passaged in mice
      (NL20T-A and -B) did not. We used these nontumorigenic (NL20 and NL20T-n) and
      tumorigenic (early passage NL20T, NL20T-A, and NL20T-B) cells to study the role
      of the alpha 5/beta 1-integrin and attachment to fibronectin in tumorigenicity.
      The two nontumorigenic cell lines (NL20 and NL20T-n) attached slower to
      fibronectin-coated plates than the two tumorigenic cell lines in a cellular
      extracellular matrix adhesion assay. Attachment was abrogated by exposure to a
      blocking antibody to the alpha 5/beta 1-integrin, the fibronectin receptor, in
      the two tumorigenic cell lines. Cell surface expression of the alpha 5/beta 1
      cell surface protein by flow cytometry was highest in the tumorigenic NL20T and
      NL20T-A cells. NL20T-A cells were cultured with an antibody to alpha 5/beta 1 and
      inoculated s.c. into athymic nude mice; tumorigenicity of the NL20T-A cells was
      inhibited in a dose-dependent manner. Tumorigenicity was also inhibited partially
      with monoclonal antibodies to either alpha 5 or beta 1. A mixture of 10%
      tumorigenic NL20T-A cells and 90% nontumorigenic NL20 cells was cultured on
      plastic, type IV collagen, laminin, and fibronectin for 9 weeks. Only cells
      cultured on fibronectin formed tumors when inoculated s.c. into athymic nude
      mice. We conclude that these data are consistent with the hypothesis that
      neoplastic transformation in our original cell line arose from in vivo selection
      of a small mutant clone, which had arisen in culture and was selected
      subsequently in vivo but was lost with in vitro culture in NL20 cells, and that
      alpha 5/beta 1-integrin interaction with the extracellular matrix may play a role
      in tumorigenicity in our system.

PMID- 8521417
TI  - Mapping of the vascular endothelial growth factor-producing hypoxic cells in
      multicellular tumor spheroids using a hypoxia-specific marker.
AB  - We have investigated the hypoxia inducibility of vascular endothelial growth
      factor (VEGF) in multicellular tumor spheroids of HT29 cells using a monoclonal
      antibody to a fluorinated bioreductive drug, EF5 [2-(2-nitro-1H-imidazol-1-yl)-N
      (2,2,3,3,3-pentafluoropropyl)aceta mide], a chemical probe for hypoxia. We have
      shown that VEGF expression is predominantly localized in interior spheroid cells
      that are sufficiently hypoxic to bioreductively activate the 2-nitroimidazole and
      produce immunologically detectable adducts of the EF5 compound. Northern blotting
      analyses demonstrated that VEGF165 is the predominant form of VEGF produced by
      HT29 cells and that the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate did
      not induce VEGF expression. This study demonstrates that VEGF expression is up
      regulated in response to hypoxia and in the microenvironments found in human
      multicellular tumor spheroids. This investigation also illustrates the utility of
      the EF5 binding in multi-cellular tumor spheroids as a means of studying the
      expression and regulation of hypoxia-inducible genes.

PMID- 8521418
TI  - 5-Ethynyluracil (776C85): effects on the antitumor activity and pharmacokinetics
      of tegafur, a prodrug of 5-fluorouracil.
AB  - We studied the effects of 5-ethynyluracil (776C85 and 776C), a potent mechanism
      based inactivator of dihydropyrimidine dehydrogenase, on the antitumor efficacy
      and pharmacokinetics of tegafur (FT), a prodrug of 5-fluorouracil (5-FU), in rats
      with large s.c. colon carcinoma. Rats were dosed p.o. once daily for 7 days with
      either FT, FT and uracil in a 1:4 molar ratio (UFT), FT 1 h after 776C (776C/FT),
      or UFT 1 h after 776C (776C/UFT). 776C, which was dosed at 1 mg/kg, had neither
      intrinsic antitumor activity nor toxicity. The rank order in antitumor efficacy
      at the maximal tolerated dose of the FT (mg/kg/day) component was 776C/FT (5
      mg/kg/day) > or = UFT (80 mg/kg/day) = 776C/UFT (5 mg/kg/day) >> FT (200
      mg/kg/day). One-hundred % of rats treated with 776C/FT had complete and sustained
      tumor regression with no severe toxicity. The area under the plasma 5-FU
      concentration versus the time curve generated from UFT, FT, and 776C/FT at their
      maximum tolerated dose was 140, 50, and 27 microM.h, respectively. The area under
      the concentration in plasma versus time curve did not correlate with the rank
      order of antitumor efficacy. The vast majority of 5-FU derived from FT (alone)
      appeared to be rapidly catabolized. Furthermore, plasma exposure of 5-FU derived
      from UFT was more variable than that from 776C/FT. Each therapy also produced
      different levels of plasma uracil. Endogenous plasma uracil levels (1-3 microM)
      were not affected by FT but increased to 100 microM after dosing with 776C.
      Plasma uracil from UFT was 800 microM 1 h after dosing. These results suggest
      that moderately elevated uracil (776C/FT) may be beneficial, whereas uracil that
      is greatly elevated during the first 5 h (UFT) and 5-FU catabolites (FT alone)
      may interfere with antitumor efficacy. 776C, coadministered with FT, could
      provide once-a-day oral therapy for cancer patients.

PMID- 8521419
TI  - O6-alkylguanine-DNA alkyltransferase attenuates triazene-induced cytotoxicity and
      tumor cell immunogenicity in murine L1210 leukemia.
AB  - Methylating and chloroethylating triazene compounds (TZCs) are effective
      antitumor agents in murine leukemias and can induce the appearance of novel
      antigens in leukemic cells (chemical xenogenization). Recently, it has been shown
      that TZCs might have a role in the treatment of patients affected by acute
      myelogenous leukemias that express low levels of the DNA repair enzyme, O6
      alkylguanine-DNA alkyltransferase (OGAT). In this report, we have evaluated the
      role of this DNA repair enzyme in the leukemic cell response to the xenogenizing
      and cytotoxic properties of TZCs. OGAT-deficient murine leukemic L1210 cells were
      transfected with a recombinant ecotropic retrovirus containing the coding region
      for the human OGAT protein. Selected clones expressed the human OGAT transcript
      and had greatly increased OGAT activity. Compared to OGAT-deficient cells, OGAT
      expressing cells were considerably more resistant to the xenogenizing properties
      of 1-(p-chlorophenyl)-3,3- dimethyl-triazene, measured in terms of leukemia graft
      rejection, and were less susceptible to the cytotoxic activity of the TZCs 8
      carbamoyl-3-methyl-imidazo [5,1-d]-1,2,3,5-tetrazin-4(3H)-one and 8-carbamoyl-3
      (2-chloroethyl)imidazo [5,1-d]-1,2,3,5-tetrazin-4(3H)-one. These data suggest
      that methylation of the O6 position of guanine is involved in the appearance of
      increased tumor immunogenicity after exposure to methylating TZC and that OGAT is
      able, at least in part, to counteract the cytotoxic effects of methylating and
      chloroethylating agents.

PMID- 8521420
TI  - Identification of melanoma inhibitory activity and other differentially expressed
      messenger RNAs in human melanoma cell lines with different metastatic capacity by
      messenger RNA differential display.
AB  - The differential display technique was used to identify mRNAs differentially
      expressed in human melanoma cell lines with different metastatic capacity. We
      report the isolation of nine different clones, of which four were uniquely
      expressed in the highly metastatic human melanoma cell line MV3, whereas the
      other five clones were uniquely expressed in the poorly metastatic human melanoma
      cell line 530. The differences in expression identified by differential mRNA
      display were confirmed by Northern blot analyses. DNA sequencing followed by
      computer search analyses indicated that of the nine differentially expressed
      clones, five represented novel gene products. The other four were
      histocompatibility antigen HLA-DR, laminin B2, melanoma inhibitory activity
      (MIA), and tissue inhibitor of metalloproteinases 3. MIA was also identified in
      RNA from human melanoma metastasis lesions in a comparison by differential
      display with pooled human nevi. Northern blot analysis confirmed MIA mRNA
      expression in nonmetastasizing melanoma cell lines and in melanoma metastasis
      lesions, while expression was absent in highly metastasizing cell lines and
      pretumor stages. In the 11 metastasis lesions examined, MIA mRNA expression was
      apparently inversely correlated with pigmentation.

PMID- 8521421
TI  - c-fos-induced osteosarcoma formation in transgenic mice: cooperativity with c-jun
      and the role of endogenous c-fos.
AB  - Transgenic mice overexpressing the c-fos proto-oncogene in bone develop
      osteosarcomas, whereas mice overexpressing c-Jun are normal. In this study, we
      investigated whether Fos and Jun would cooperate in vivo and whether the
      threshold levels of Fos are important in osteosarcoma formation. Fos-Jun double
      transgenic mice develop osteosarcomas at a higher frequency than single-Fos
      transgenic mice with no differences in the time of onset of tumor formation.
      Histological and histochemical analyses indicated that Fos-Jun tumors contained
      greater quantities of neoplastic bone, were more remodeled, and contained a
      greater number of multinucleated osteoclast-like cells than tumors isolated from
      age-matched, single transgenic littermates. In contrast, overexpression of Fos in
      knockout mice that lack endogenous Fos resulted in a decrease in the number of
      tumor-bearing mice; osteosarcomas were almost absent in c-fos -/- mice, whereas
      tumor incidence was reduced to approximately 50% in c-fos +/- mice. Cell lines
      isolated from Fos-Jun transgenic tumors expressed high levels of both transgenes
      but significantly lower levels of the jun-related gene junB compared with cells
      expressing only a c-fos transgene. Osteoblastic marker genes were expressed at
      varying levels in different cell lines, but expression of interstitial
      collagenase (matrix metalloproteinase-1) was enhanced in cells derived from Fos
      Jun tumors. These studies demonstrate that coexpression of a c-jun transgene can
      enhance Fos-induced oncogenesis in vivo and suggest that a critical level of Fos
      is necessary for osteosarcoma development.

PMID- 8521422
TI  - [Nicardipine attenuates the sympathetic reflex of orthostatism: do
      dihydropyridine-sensitive calcium channels regulate noradrenaline release?].
AB  - Twelve hypertensive subjects were treated for 2 weeks with the dihydropyridine
      calcium channel antagonist nicardipine (40 mg daily) according to a double-blind,
      placebo-controlled study protocol. Nicardipine treatment significantly decreased
      systolic and diastolic blood pressure and increased plasma noradrenaline levels
      measured at supine rest. However, the treatment significantly inhibited the
      physiological increase of circulating neurotransmitter following sympathetic
      stimulation induced by orthostatism. These results suggest that dihydropyridine
      sensitive calcium channels may modulate the noradrenaline release from nerve
      terminals of the peripheral sympathetic nervous system.

PMID- 8521423
TI  - [Diagnosis and assessment of thrombolytic efficacy in left atrial thrombosis
      using transesophageal echocardiography].
AB  - In order to evaluate the incidence of atrial thrombosis 17 patients underwent
      transesophageal echocardiography (TEE). They were referred to our department
      because of a recent systemic embolic event and we found thrombi located in the
      left atrial appendage in 14 patients, in 5 cases in the left atrium and in 4
      cases in the right atrium. Transthoracic echocardiography showed left atrial
      masses in 5 patients. Transesophageal echocardiography was more sensitive than
      transthoracic echocardiography in detecting atrial thrombi. Fifteen patients were
      treated with thrombolytic therapy using urokinase or rt-PA. To evaluate the
      efficacy of thrombolysis, we repeated TEE immediately after the infusion and 24
      hours later. We observed a reduction of the mass of thrombi in all patients; the
      effect of therapy was not different 24 hours later. Our study underlines the
      diagnostic power of TEE in detecting atrial thrombosis and also suggests the use
      of TEE in the evaluation of the efficacy of thrombolytic therapy.

PMID- 8521424
TI  - [The reduction of beta-adrenoceptor density and the suppression of ectopic
      ventricular activity with low doses of amiodarone].
AB  - In 5 patients with frequent premature ventricular ectopic beats, refractory to
      other antiarrhythmic treatments, amiodarone, given orally at the dose of 200 mg
      once a day for 4 weeks, reduced beta-adrenoceptor density from 202.9 +/- 62 to
      101.1 +/- 33 fmol/mg protein (p < 0.01). Similarly, kd decreased from 21.0 +/- 6
      to 3.9 +/- 1 (p < 0.05). Changes in beta-adrenoceptor population were accompanied
      by a marked reduction in mean premature ventricular complexes (PVC) frequency
      from the control value of 428.9 +/- 150.3 to 13.4 +/- 10.7 PVC/h (p < 0.05) and
      by a decrease in heart rate, from 83.8 +/- 4 to 73.9 +/- 4 b/min (p < 0.01). On
      the contrary, mean arterial pressure remained unchanged. Patients did not show
      side effects during treatment. Therefore, low dose oral amiodarone has important
      pharmacologic and therapeutic effects. It significantly reduces lymphocyte beta
      adrenoceptor density and is effective in treatment of ventricular arrhythmias.
      Additional studies were performed in vitro exposing lymphocytes to increasing
      concentrations of amiodarone. The analysis of variance for repeated measures
      showed that amiodarone-induced reduction in lymphocyte beta-adrenoceptor density
      is a dose-depending phenomenon. Accordingly, treatment with doses of amiodarone
      higher than that used in the present study may induce a major reduction in
      lymphocyte beta-receptor density and exert a depressant cardiac effect.

PMID- 8521425
TI  - [The effect of a territorial health emergency service on the delay in the
      hospitalization of patients with an acute myocardial infarct].
AB  - In July 1987 a prehospital emergency medical service (EMS) was activated in
      Verona (Italy) and a broad educational campaign was introduced. Prehospital care
      is delivered by emergency physicians and/or qualified nursing staff, who travel
      by ambulance or helicopter and have radio contact with the hospital alarm centre.
      During a 1-year period before the activation of the EMS, 476 patients with acute
      myocardial infarction (AMI) were admitted to the coronary care unit (CCU) of
      Verona, with a median delay time of 4 hours. In the period between July 1990 and
      June 1991, 412 patients were admitted, with a median delay time of 3 hours. Age,
      gender, previous AMI and infarct location were not related to delay time. In the
      second period, 34% patients used the EMS, while 66% used their own transport. In
      patients who used the EMS, median delay time was 2 hours (1 hour and 20 min
      shorter, p < 0.01, than in patients who did not). The time between symptoms onset
      and reaching the decision that medical care should be sought (1 hour and 18 min)
      was the longest component of the total delay time. The time from EMS call to
      hospital arrival was 25 min and the time which elapsed in the Emergency
      Department before reaching the CCU was 15 min. In these patients, decision time
      and Emergency Department time were significantly shorter (p < 0.01) than in
      patients who did not use the EMS. We conclude that the EMS is effective in
      reducing delay time in patients with AMI.

PMID- 8521426
TI  - [The evaluation of atherosclerotic lesions of the extracranial carotid arteries
      in hypertensive subjects. A study by B-mode and pulsed Doppler echotomography].
AB  - Arterial hypertension is considered an independent atherosclerotic risk factor.
      In hypertensive patients it increases cardiovascular morbidity and mortality
      risk. The aim of the study was to emphasize the presence of atherosclerotic
      lesions at the level of extracranial carotid tree in patients with essential
      arterial hypertension. In 110 hypertensive patients (63 males, 47 females) mean
      age 66 +/- 16 years, and in 100 normotensive patients (66 males, 34 females) mean
      age 65 +/- 15 years, high-resolution B-mode pulsed wave Doppler echotomography of
      internal, external and common carotid artery of both sides was performed. The
      value of the intimal-medial complex thickness of common carotid was measured, and
      the stenosis percentage evaluated by B-mode pulsed wave Doppler echotomography.
      Atherosclerotic plaques were classified according to their echogenic
      characteristic and surface; their localization was then evaluated. In
      hypertensive patients we observed the presence of common carotid intimal-medial
      thickening in 75.4%, atherosclerotic plaques in 60.9% and stenosis in 17.9%;
      58.3% of these ones were localized at internal carotid, 33.3% at common carotid
      and 8.3% at external carotid. We observed that 36% of the 100 normotensive
      patients presented common carotid intimal-medial thickening (p < 0.001 versus
      hypertensives), 25% atherosclerotic plaques (p < 0.001 versus hypertensives) and
      8% stenoses; 50% of these stenosis were localized at internal carotid, the second
      half at external carotid. In conclusion, high-resolution B-mode echotomography
      study with pulsed wave Doppler spectral analysis represents a necessary method to
      evaluate the condition of the extracranial carotid tree in patients with
      hypertension.

PMID- 8521427
TI  - [The epidemiology of heart failure: its incidence, prevalence and mortality. The
      data and uncertainties].

PMID- 8521428
TI  - Treatment of refractory heart failure.

PMID- 8521429
TI  - [A case of oxalosis with heart and lung involvement].
AB  - We report the case of a 37-year-old woman with oxalosis, and cardiopulmonary
      involvement. Two-dimensional and Doppler echocardiography disclosed intracardiac
      calcifications compatible with deposition of calcium oxalate, and severe chronic
      pulmonary hypertension. Endomyocardial biopsy showed interstitial deposition of
      calcium oxalate. The absence of severe cardiac disease strengthened a deposition
      of calcium oxalate even in the arteries of the lungs, with secondary chronic
      pulmonary hypertension.

PMID- 8521430
TI  - [Another case of dissecting aortic aneurysm with familial incidence].
AB  - Several authors have reported aortic dissection in Marfan's syndrome with
      familial incidence. Cases of dissecting aortic aneurysms have likewise been
      described in families whose members had severe systemic arterial hypertension. We
      report 4 cases of familial aortic aneurysm, 3 of whom had a dissection, in the
      absence of Marfan's phenotype but with histologic findings and genetic
      transmission similar to those previously described as formes frustes of Marfan's
      syndrome.

PMID- 8521431
TI  - Fluoride varnish versus acidulated phosphate fluoride gel: a 3-year clinical
      trial.
AB  - The aim of this trial was to compare the caries-preventive effect of sodium
      fluoride varnish and acidulated phosphate fluoride (APF) gel. A total of 254
      children aged 12-13 years with high past caries experience were randomly divided
      into two groups. The participants received semi-annual applications of either
      fluoride varnish or APF gel for 3 years. During the study, the mean (+/- SD)
      total DMFS increments of the varnish and gel groups were 6.8 +/- 5.6 and 7.7 +/-
      6.4, respectively, when initial caries was included, and 3.1 +/- 3.7 and 3.6 +/-
      4.6 when initial caries was excluded. The difference was most evident on the
      approximal surfaces (varnish: 1.4 +/- 2.4; gel: 1.9 +/- 3.1). However, this
      difference was not statistically significant. Although larger studies are needed
      for firm conclusions about the comparative effect of the two fluoride measures,
      the results suggest that fluoride varnish is as effective as fluoride gel at
      least in preventing approximal caries. Taking into account the shorter treatment
      time, using fluoride varnish for professional applications seems justified.

PMID- 8521432
TI  - Three-year randomized trial of professionally applied topical fluoride gel
      comparing annual and biannual applications with/without prior prophylaxis.
AB  - The twice yearly application to children's teeth of acidulated phosphate fluoride
      (APF) gel in dental trays preceded by a professionally rendered 'dental
      prophylaxis' has become the standard and most commonly used dental chairside
      procedure for prevention of dental caries. This study was a randomized, 3-year,
      community-based clinical trial of professionally applied APF gel involving the
      use and non-use of a prior dental prophylaxis and annual and biannual APF
      applications for children in age groups 6-7 (n = 176) and 10-11 (n = 153) years
      initially, who are likely at high risk of future dental caries. The 3-year
      results of this study show no significant effect on dental caries reduction of
      either a prior prophylaxis or annual versus biannual APF gel applications. A
      significant reduction in the frequency of provision of these dental services,
      limited to high caries risk patients only, is recommended.

PMID- 8521433
TI  - Effect of post-brushing water rinsing on caries-like lesions at approximal and
      buccal sites.
AB  - The aim was to study the effect of two different water rinsing procedures after
      toothbrushing with an NaF-containing dentifrice on the degree of de- or
      remineralization of enamel and dentine at approximal and buccal sites. Seven
      adults, wearing complete dentures, participated in two experimental periods (A
      and B) in a randomised order. During period A, they brushed with the dentifrice
      for 2 min, followed by 1-min active mouthrinse with the toothpaste-foam combined
      with 10 ml of water. No more water was used after the slurry had been spat out.
      During period B, the brushing was followed by 3 thorough rinsings of
      approximately 15 ml water each. These two procedures were carried out twice
      daily, i.e. in the morning (after breakfast) and in the evening (just before
      bedtime), during 3 months. Demineralized enamel and dentine samples were mounted
      at two locations--approximally and buccally--in the first molar region of the
      upper prostheses. Quantitative microradiography (TMR) was used to assess the
      lesion depth (ld) and the mineral loss (delta Z). The results showed that the
      approximally located samples continued to lose mineral during both periods A and
      B. However, the ld and delta Z values for enamel (p < 0.01) and dentine (p <
      0.05) increased less during A than B. The buccally located enamel and dentine
      samples remineralized during the experiment, but no statistically significant
      differences were found for the ld and delta Z values of either enamel or dentine
      between periods A and B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521434
TI  - Prediction of dental caries development in 1-year-old children.
AB  - Dietary habits, oral hygiene, fluoride exposure and occurrence of mutans
      streptococci were studied in 1-year-old children (n = 786) as well as the socio
      economic and immigrant background of their parents. The purpose was to evaluate
      the predictive ability of variables studied in 1-year-old children that could be
      used to identify children at risk for early caries development. In a multivariate
      logistic regression analysis, the variables significantly associated with caries
      at 3.5 years of age were immigrant background (p < 0.001), mother's education (p
      < 0.001), consumption of sugar-containing beverages (p < 0.001), mutans
      streptococci (p < 0.05) and candy (p < 0.05). The probability of caries
      development was 87% when all the variables associated with caries were present at
      1 year of age. The relative risk (odds ratio) of those children to develop
      manifest caries at 3.5 years of age was estimated to be 32 times higher than in
      the children where corresponding risk factors were not present. The results
      indicate that prediction at 1 year of age, built on risk factors associated with
      dental caries, can provide an indication of possible preventive interventions.

PMID- 8521435
TI  - Prediction of the erosive potential of some beverages.
AB  - The aim of this study was to investigate whether the erosive potential of a
      beverage on human enamel can be predicted by examining the composition of the
      beverage. The buccal surfaces of 84 caries-free premolars were embedded in resin
      and polished flat. Two hundred micrometers of the enamel surface were removed.
      Then the slabs were divided into 14 groups and immersed for 20 min in
      commercially available beverages. Surface microhardness was measured before and
      after immersion. Further, the phosphate concentration, the fluoride
      concentration, the baseline pH as well as the titrated amount of base to raise
      the pH to 7.0 of each beverage were determined. Surface microhardness values
      after immersion were calculated with an equation derived in a recent study and
      compared with the values measured in this investigation. Apple juice showed the
      greatest significant decrease (p < 0.05) in surface microhardness, followed by
      Schweppes, Orangina and Grapefruit soft drink. The smallest decrease in surface
      microhardness that was significant resulted from Fendant and Isostar orange. The
      mean absolute deviation of the calculated to the effective erosion was 7.1%, it
      ranged between 14.6% (apple juice) and 1.6% (Fendant). The data suggest the
      possibility of predicting erosion caused by a beverage with an accuracy of 7%.
      This information can be of value in the prevention of dental erosion.

PMID- 8521436
TI  - Radiographic evaluation of occlusal caries: effect of training and experience.
AB  - The purpose of this study was to investigate what effect differing levels of
      didactic education and clinical experience have on the ability to diagnose
      occlusal caries from radiographs. Freshman and senior dental students and dental
      school faculty were asked to evaluate bitewing radiographs for the presence of
      occlusal caries and for a recommendation for restorative treatment. The agreement
      between histologic and radiographic diagnosis was assessed by calculating
      sensitivity, specificity, accuracy, and interexaminer agreement. It was concluded
      that dental students and faculty did differ in their abilities to evaluate
      radiographs for occlusal caries, and that education and clinical experience
      especially affected interexaminer agreement.

PMID- 8521437
TI  - Stereomicroscopy, film radiography, microradiography and naked-eye inspection of
      tooth sections as validation for occlusal caries diagnosis.
AB  - In establishing a trustworthy validation for occlusal caries lesions, various
      methods have been used after sectioning teeth. The aim of the present study was
      to compare the accuracy of four such methods: stereomicroscopy (SM), film
      radiography (FR), microradiography (MR) and naked-eye inspection (NEI) for the
      detection of caries in occlusal tooth surfaces. Further, the interobserver
      agreement between three observers' registrations of occlusal caries by these
      methods was evaluated. The material consisted of 18 unerupted third molars known
      to be sound with respect to caries, as they were embedded in bone prior to
      removal, and 20 erupted third molars with an unknown 'true state of disease'. The
      teeth were serially sectioned, coded and examined blindly for occlusal caries by
      three independent observers by the four validation methods under study. SM was
      demonstrated to be the only method by which all observers correctly identified
      all 18 unerupted teeth as sound, resulting in a specificity of 1.00. By the other
      three methods, 1 or more of the unerupted teeth were falsely classified as
      carious. In the erupted teeth, 73, 58, 52 and 32%, respectively, of the teeth
      were determined carious by SM, MR, NEI and FR. As it was possible by SM to detect
      caries in nearly three quarters of the erupted teeth and at the same time to
      identify all unerupted teeth as sound, this method seemed to be the most
      trustworthy of the validation methods under study.

PMID- 8521438
TI  - Factors involved in validity measurements of diagnostic tests for approximal
      caries--a meta-analysis.
AB  - In this study, a meta-analysis was performed on published validity parameters of
      visual inspection, radiographic examination and visual inspection upon fibreoptic
      transillumination (FOTI) in approximal caries diagnosis. It was the objective to
      investigate the influence of the diagnostic test, the study design and the
      validation method on reported validity. Sensitivities and specificities reported
      in the literature were transformed into D2 values, representing the performance
      of a diagnostic method above chance, or of the observer using it, in a single
      parameter. Dz values were neither statistically significantly different between
      visual inspection, radiographic examination and FOTI nor between 'weak' and
      'strong' validation methods (p > 0.05). Dz values obtained from in vivo studies
      were significantly different from those obtained from in vitro studies (p <
      0.05), indicating that study design had a significant impact on the measurement
      of the validity of the evaluated test for approximal caries diagnosis.

PMID- 8521439
TI  - Grey discolouration and marginal fracture for the diagnosis of secondary caries
      in molars with occlusal amalgam restorations: an in vitro study.
AB  - Grey discolouration of the enamel around a filling and marginal fracture are
      often reasons to replace restorations due to suspicion of secondary caries. The
      aim of this study was to establish the validity of grey discolouration and
      marginal fracture for the diagnosis of caries at the enamel-dentine junction
      (EDJ) next to an amalgam filling. The occlusal surfaces of 161 extracted molars
      with occlusal amalgam fillings were photographed on colour slides, from which
      grey discolourations and marginal fracture were recorded. The size of the
      fracture was scored using a modified Mahler scale with six categories: score 1 =
      no marginal fracture (< 30 microns), score 6 = fracture width > 200 microns.
      Secondary caries at the EDJ was scored on radiographs of 700 micron sections of
      the molars. Both radiolucencies and radiopacities in dentine were scored as
      caries. The sensitivity of grey discolouration for detection of secondary caries
      was 50% and the specificity 91%. The positive and negative predictive values were
      71 and 80%, respectively. Marginal fracture was evaluated at five different
      levels of severity. Although there was caries present more frequently at the EDJ
      under severely fractured margins, marginal fracture was found of little
      diagnostic value at all levels. Only marginal fracture at threshold level V
      provided a positive predictive value (50%), which was significantly higher than
      the caries prevalence (31%). It is concluded that width of marginal fracture, as
      defined by the Mahler scale, has hardly any value for the diagnosis of secondary
      caries. However, grey discolouration may be a useful diagnostic aid.

PMID- 8521440
TI  - The effect of placing a clear pit and fissure sealant on the validity and
      reproducibility of occlusal caries diagnosis.
AB  - The purpose of this in vitro study was to assess the validity and reproducibility
      of the diagnosis of fissure caries prior to and following the placement of a
      clear sealant. One hundred and twelve extracted molar teeth were examined by 7
      experienced clinicians. Each examiner conducted four visual examinations, 2 prior
      to and 2 after sealing, allowing an assessment of reproducibility. The teeth were
      subsequently serially sectioned to provide the histological validation. After
      placement of a sealant, a significant (p < 0.05) loss of sensitivity was found
      for the diagnosis of enamel lesions and dentine lesions, but specificity was not
      altered. The overall reproducibility expressed by the kappa statistic was 0.60
      and 0.47, before and after sealing, respectively. The examiners significantly (p
      < 0.001) underestimated the severity of lesions detected after sealing compared
      to their assessment prior to sealing. The investigation suggests that sealed
      surfaces require careful assessment and monitoring.

PMID- 8521441
TI  - Human root caries: microbiota in plaque covering sound, carious and arrested
      carious root surfaces.
AB  - The plaque microbiota covering sound or carious root surfaces were studied and
      compared with that covering arrested root caries lesions. From each of these
      categories five extracted teeth were examined. The experimental design of the
      study allowed us to relate the qualitative and quantitative microbial composition
      to the degree of integrity of the root surface. Plaque was sampled by a newly
      developed 'mowing' technique. Plaque samples were cultured anaerobically on
      nonselective Columbia blood agar plates supplemented with 5% hemolyzed human
      blood and on media selective for Lactobacillus spp. and streptococci of the
      mutans group. The cultivable microbiota were quantitatively speciated using Rapid
      ID 32A, Rapid ID 32 Strep, API 20 Strep, API ZYM, and API 50 CH tests and SDS-PAG
      electrophoresis. Regardless of the state of mineralization, the microbiota on all
      surfaces resembled marginal plaque associated with gingivitis. In addition to the
      gram-positive predominant facultative anaerobic genera Streptococcus,
      Staphylococcus, Lactobacillus and Actinomyces, gram-negative anaerobes,
      predominantly Bacteroides, Prevotella, Selenomonas, Fusobacterium, Leptotrichia,
      and Capnocytophaga, showed the highest isolation frequencies. On all surfaces
      Actinomyces spp. predominated, with streptococci and lactobacilli forming a minor
      part of the microbiota. With respect to the detected proportions of anaerobes,
      microaerophiles, Actinomyces naeslundii, Prevotella buccae and Selenomonas
      dianae, significant differences were observed between the three categories of
      root surfaces. The total CFU's on both caries-free and caries-active surfaces
      were significantly higher than on arrested lesions. In general, the results
      support a polymicrobial etiology for caries initiation on root surfaces, with A.
      naeslundii, Capnocytophaga spp., and Prevotella spp. making specific
      contributions to the processes of cementum and dentin breakdown.

PMID- 8521442
TI  - Sucrose retention and colonization by mutans streptococci at different sites of
      the dentition.
AB  - The correlations between the retention and elimination of sucrose at different
      oral sites and the colonization by mutans streptococci at the same sites were
      tested in 10 subjects with > 10(5) mutans streptococci per millilitre of saliva.
      Paraffin-stimulated saliva was collected and plaque samples were taken with a
      toothpick from all the buccal surfaces except the third molars. One week after
      the plaque sampling, the sucrose clearance was determined. After a mouth rinse
      with 10 ml of a 10% sucrose solution, pre-weighed filter paper discs were placed
      at representative buccal sites of the interdental papilla between molars,
      premolars and incisors in the upper and lower jaw. The samples were collected
      0.5, 2.5, 5.5, 8.5 and 12.5 min after rinsing. Analysis of the sucrose
      concentration was made using an enzymatic method. The oral sugar clearance was
      slower in the anterior region of the upper jaw than in the posterior regions and
      in the central region of the lower jaw. The frequency of mutans streptococci
      decreased towards the anterior teeth, with Streptococcus sobrinus predominating
      over Streptococcus mutans. A negative correlation was observed in the upper jaw
      between sugar clearance and retention and the prevalence of mutans streptococci,
      whereas the opposite tendency was observed in the lower jaw.

PMID- 8521443
TI  - Acid production by human strains of Streptococcus mutans and Streptococcus
      sobrinus.
AB  - Acid production by washed suspensions of human strains of Streptococcus mutans (n
      = 18) and Streptococcus sobrinus (n = 12) was measured. The strains were isolated
      from infants and adolescents with varying caries experience. Some of these
      strains and two laboratory strains (1 S. mutans and 1 S. sobrinus) had been
      tested in an earlier study for their cariogenicity in hamsters. Further, 3
      Streptococcus sanguis strains and 1 S. sobrinus laboratory strain were included.
      Acid production was determined in repeated titration experiments at a constant pH
      of 5.5. Higher mean acid production activities (p < 0.05) were obtained by S.
      sobrinus compared with both S. mutans and S. sanguis. However, large variations
      among the strains were found both between and within the species. No clear
      relationship was found between the glycolytic activity of strains and the caries
      prevalence of the children from whom the strains had been isolated or the caries
      scores in a hamster model. In conclusion, although both S. mutans and S. sobrinus
      have aciduric and acidogenic properties, it is difficult to relate the acid
      production activity of pure cultures in vitro to the caries process in vivo.

PMID- 8521444
TI  - Identification and genetic characterisation of melibiose-negative isolates of
      Streptococcus mutans.
AB  - Streptococcus mutans is frequently identified on the basis of phenotypic
      characteristics such as the ability to ferment carbohydrates. The usefulness of
      some of these identification tests may be limited in the case of isolates which
      are atypical with regard to their fermentation properties. We previously
      identified isolates of S. mutans which were unable to ferment melibiose, a
      characteristic which is included in some typing schemes. In all of these isolates
      there was a large chromosomal deletion which included the multiple sugar
      metabolism (msm) operon which encodes several genes involved in the uptake and
      metabolism of a number of sugars including melibiose. In the present study, sugar
      fermentation tests, ribotyping, colony hybridisation with DNA probes and
      polymerase chain reaction (PCR) were used to investigate the relatedness of these
      atypical isolates. The PCR and colony hybridisation procedures were based on
      amplification and detection of two genes: the wapA gene which encodes a surface
      protein found in all S. mutans strains and the gtfA gene which lies within the
      msm operon. The colony hybridisation and PCR results confirmed loss of the gtfA
      gene in the melibiose-negative isolates. Three new melibiose-negative isolates
      were also identified, but in only 2 of these was the gtfA gene absent, the third
      did not appear to have lost this region of the chromosome. Biotyping, as well as
      ribotyping based on an EcoRI digest of chromosomal DNA, revealed that the
      melibiose-negative isolates fell into a number of distinct groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8521445
TI  - Interaction of chlorhexidine with cytoplasmic membranes of Streptococcus mutans
      GS-5.
AB  - Cytoplasmic membranes of Streptococcus mutans GS-5 were extracted by incubating
      cells with 1% sodium lauroyl sarcosinate for 20 min at room temperature. The
      profiles of membrane proteins were determined by SDS-PAGE and isoelectric
      focusing. The effect of chlorhexidine digluconate on cell membranes was studied
      after treating the extracted proteins for 30 min with the drug at final
      concentrations of 0.05 and 0.2%. Chlorhexidine caused selective reduction in the
      intensity of the membrane proteins. Five densely staining bands with molecular
      weights of 24.2, 19.6, 18.1, 17.6 and 16.4 kD were obviously diminished.
      Isoelectric focusing indicated that chlorhexidine preferably precipitated acidic
      cytoplasmic proteins (pI 4.0-4.92). Our results are consistent with the
      hypothesis that the mode of action of this drug is mainly attributed to its
      hydrophilic property. Chlorhexidine, being cationic, may interact with bacteria
      by attraction to negative-charge membrane components.

PMID- 8521446
TI  - Precise control of the frequency and amount of food provided for small laboratory
      animals by a new electronic metering technique, used to evaluate the cariogenic
      potential of chocolate.
AB  - A new electronic system was set up for accurately regulating the amount and
      frequency of food dispensed to laboratory rats so that investigations of the
      cariogenic potential of foods can be carried out under strictly controlled
      conditions according to the stipulations of the San Antonio Consensus Conference,
      1985. The system was used to evaluate the cariogenicity of sucrose incorporated
      into plain and milk chocolate. The results suggested that 18.75% of sucrose in
      the diet had the same cariogenic potential no matter whether it was in the form
      of fine crystals or incorporated into plain chocolate, but mean caries scores
      were nearly 30% higher on a plain chocolate than on a milk chocolate regime.

PMID- 8521447
TI  - Effect of extrinsic fluoride concentration on the uptake and release of fluoride
      from two glass ionomer cements.

PMID- 8521448
TI  - Redirection of cellular cytotoxicity. A two-step approach using recombinant
      single-chain Fv molecules.
AB  - In this article the authors discuss an indirect system for redirecting cellular
      cytotoxicity, which utilizes a "universal" bispecific antibody to redirect T
      cells to kill cells targeted with single-chain Fv (sFv) fusion proteins that
      carry a peptide tag recognized by the bispecific antibody. This approach has a
      number of theoretical advantages in the immunotherapy of cancer.

PMID- 8521450
TI  - Linkage of silver to antibodies through 2-imino thiolane.
AB  - Earlier studies described the linkage of silver to antibodies using SH groups
      generated by the reduction of the SS groups using ascorbic acid (1) analogous to
      the Thakur and DeFulvio technique for linking technetium to antibodies. This work
      describes the linkage of silver to IgG after introducing SH groups by coupling
      the IgG to 2-imino thiolane. The protein was dissolved in sodium acetate buffer
      pH 4.5 containing 1 mM EDTA by dialysis/gel chromatography in a concentration of
      20 mg/mL. 2-Imino thiolane dissolved in Tris-HCl acetate buffer, pH 8.2, 0.2M was
      added to give a final dilution of 0.2 mM 2-imino thiolane. The excess of 2-imino
      thiolane was removed by dialysis or G-25 Sephadex gel chromatography and then the
      protein was reacted with silver nitrate 0.1 mM. The unreacted SH groups were
      blocked by adding iodoacetamide to a concentration of 5 mM. The nonprotein
      reagents again were removed by dialysis or gel chromatography. The thiol groups
      were titrated using 1.5 mM 2 2-Py-SS-Py prior to and after addition of silver. It
      was observed that depending on the concentration of silver, 50-80% of the SH
      groups were coupled to silver. Higher concentrations of silver led to insoluble
      precipitates and should be avoided.

PMID- 8521449
TI  - Pharmacokinetics of reshaped MAb 425 in three animal species.
AB  - The murine monoclonal antibody (MAb) 425 (mMAb 425) directed against the human
      EGFR (epidermal growth factor receptor) was reshaped (rMAb 425) in order to
      improve its therapeutical potential in humans. The pharmacokinetic properties of
      [125I]-mMAb and [125I]-rMAb 425 were compared in three animal species. Whereas
      the clearance curves of both antibodies decreased biphasically in rats and nude
      mice bearing human mammary carcinoma, a monophasic decline was observed in
      Cynomolgus monkeys. Plasma elimination half-lives of murine and reshaped MAb 425
      were similar, short in the monkey (26 h for mMAb 425 and 31 h for rMAb 425) and
      long in rats (240 h for mMAb 425 and 225 h for rMAb 425). In xenografted nude
      mice however, the half-life of mMAb 425 (203 h) was about twice as long as that
      of rMAb 425 (124 h). The half-lives of intact rMAb 425 in the three species
      obtained by ELISA differed at most by a factor of two from those obtained by
      radioactivity measurements. Biodistribution studies of [125I]-rMAb 425 revealed a
      tumor/blood ratio of 1.2 on d 1 and 5.1 on d 18, respectively. Fifty-four and
      thirty-eight percent of the radioactive dose were excreted with urine in nude
      mice (within 12 d) and rats (within 11 d), respectively. Specific localization of
      [125I]-rMAb 425 in human mammary carcinoma xenografted to nude mice was
      demonstrated.

PMID- 8521451
TI  - Bacterial expression and refolding of single-chain Fv fragments with C-terminal
      cysteines.
AB  - Two antibody single-chain Fv (scFv) fragments carrying five C-terminal histidine
      residues were expressed in Escherichia coli as periplasmic inclusion bodies.
      Their variable heavy (VH) and light (VL) domains are derived from the mouse
      monoclonal antibody 215 (MAb215), specific for the largest subunit of RNA
      polymerase II of Drosophila melanogaster and rat MAb Yol1/34, specific for pig
      brain alpha-tubulin. ScFv-215 contains an additional cysteine residue near to its
      C-terminus. After solubilization of inclusion bodies followed by immobilized
      metal affinity chromatography (IMAC) in 6M urea and a renaturation procedure,
      scFv monomers, noncovalent dimers, and aggregated antibody fragments were
      separated by size exclusion chromatography. In addition, a fraction of disulfide
      bonded scFv-215 homodimers (scFv')2 was also isolated. The various antibody forms
      appear to be in equilibrium after renaturation since first peak composed mainly
      of aggregates could be resolved into a similar pattern of aggregates, dimers, and
      monomers after repeating the denaturation/renaturation procedure. All fractions
      of the recombinant scFv-215 demonstrated high antigen-binding activity and
      specificity as shown by enzyme-linked immunosorbent assay (ELISA) and Western
      blot analysis. Affinity measurements carried out by competitive immunoassays
      showed that covalently linked (scFv')2 have binding constants quite close to
      those of the parental MAbs and fourfold higher than scFv' monomers. ScFv
      derivatives, specifically biotinylated through the free sulfhydryl group,
      recognize the corresponding antigen in ELISA and Western blot analysis, thus
      demonstrating the possibility of using chemically modified scFv antibodies for
      immunodetection.

PMID- 8521453
TI  - A re-evaluation of the apparent effects of luminal Ca2+ on inositol 1,4,5
      trisphosphate-induced Ca2+ release.
AB  - It has been suggested that the release of Ca2+ from intracellular stores by
      inositol 1,4,5-trisphosphate (InsP3) is modulated by the luminal Ca2+ content of
      the stores and that such an effect could underlie the apparent 'quantal' nature
      of InsP3-induced release. Although initial studies failed to find evidence in
      support of such a modulation, several subsequent reports have indicated luminal
      Ca2+ effects that become apparent only after a greater than 70-75% depletion of
      Ca2+ stores. In these studies, Ca2+ release was expressed as a percentage of an
      A23187-releasable pool which comprised both InsP3-sensitive and InsP3-insensitive
      components. In model calculations we have found that the presence of even a minor
      InsP3-insensitive component in the total Ca2+ pool significantly distorts
      interpretation of the data. We show that the published results can be accurately
      duplicated without any requirement for a shift in the true InsP3 sensitivity of
      Ca2+ release if either: (a) the InsP3-insensitive component does not remain a
      constant proportion of the total pool during depletion (i.e. depletion
      disproportionally affects the InsP3-sensitive component); or (b) during
      generation of InsP3-response curves, additional Ca2+ is released from the InsP3
      insensitive component as the InsP3-sensitive component is progressively emptied.
      Examination indicates that either, or both, of these conditions apply in the
      published reports and we conclude that the demonstrated effects of luminal Ca2+
      may be artifacts.

PMID- 8521452
TI  - Expression of nm23-H1 gene product in thyroid, ovary, and breast cancers.
AB  - The nm23 gene product is one of several possible mediators of cancer invasion and
      metastasis. As the amounts of nm23-H1 mRNA and gene product are reduced in
      metastatic lymph nodes from patients with papillary carcinoma of the thyroid, we
      examined the expression of nm23 gene product in 115 thyroid cancers, 78 ovarian
      cancers, 63 breast cancers, and metastatic lymph node tissues by
      immunohistochemistry. It was found that nm23-H1, but not nm23-H2 gene product,
      was expressed in primary sites of thyroid, ovarian, and breast cancers, except
      for medullary and anaplastic carcinomas of the thyroid, but expressed only weakly
      or poorly in metastatic lymph nodes. Although nm23-H1 gene product expression was
      lower in anaplastic and medullary carcinomas of the thyroid, there was no
      significant difference in nm23-H1 gene product expression among histological
      types of ovarian and breast cancers. Our data indicate that the nm23-H1 gene
      product may play a role in metastasis in these hormone-producing organs and that
      other factors may be involved in metastasis of anaplastic and medullary
      carcinomas of the thyroid.

PMID- 8521454
TI  - Arachidonate and other fatty acids mobilize Ca2+ ions and stimulate beta
      glucuronidase release in a Ca(2+)-dependent fashion from undifferentiated HL-60
      cells.
AB  - Arachidonate (1-300 microM) mobilized Ca2+ ions from an intracellular store and
      stimulated the entry of Ca2+ ions from the extracellular fluid in
      undifferentiated HL-60 cells that had been loaded with Fura-2. The integrated
      response was biphasic in form: arachidonate liberated Ca2+ ions from the
      intracellular store first, resulting in a transient increase in cytosolic free
      Ca2+ concentration ([Ca2+]i). Ca2+ entry from the extracellular fluid was not
      evident for a further 1-2 min. At baseline, [Ca2+]i was 48.1 +/- 14.0 nM (SEM, n
      = 5). Upon addition of arachidonate (100 microM), [Ca2+]i rose to a transient
      peak level of 217 +/- 38.6 nM (SEM, n = 5) and a later plateau level of 427 +/-
      118 nM (SEM, n = 5). Removal of added Ca2+ ions from the extracellular fluid in
      the presence of EGTA (1.0 mM) had no effect on the initial transient response but
      abolished the second phase of the response. In HL-60 cells that had been loaded
      with BAPTA/AM, the initial transient phase of the response was abolished but the
      elevation in [Ca2+]i due to Ca2+ entry from the extracellular fluid was
      unaffected. Undifferentiated HL-60 cells also responded to arachidonate (100
      microM) with an increase in the release of the lysosomal enzyme beta
      glucuronidase. Arachidonate-induced beta-glucuronidase release from BAPTA-loaded
      cells or in control cells exposed to Ca(2+)-free solutions was inhibited by about
      50%. In BAPTA-loaded cells that were incubated with Ca(2+)-free solutions,
      arachidonate-induced beta-glucuronidase release was inhibited by about 90%.
      Leukotriene B4 failed to elevate [Ca2+]i in the concentration range 0.01-1 microM
      and failed to activate beta-glucuronidase release in concentrations up to 10
      microM. Furthermore, the cyclo-oxygenase/lipoxygenase inhibitor ETYA (100 microM)
      was without effect on secretion. Consistent with this finding, we found that a
      large number of unsaturated fatty acids could reproduce the effect of
      arachidonate on [Ca2+]i and beta-glucuronidase release. Fatty acids belonging to
      the omega-3, omega-6 and omega-7 unsaturated fatty acid families were effective
      in elevating [Ca2+]i and stimulating beta-glucuronidase release. However, three
      unsaturated fatty acids, all belonging to the omega-9 fatty acid family, were
      ineffective.

PMID- 8521455
TI  - Cytoplasmic calcium buffer capacity determined with Nitr-5 and DM-nitrophen.
AB  - We have examined intracellular calcium buffer capacity of cytoplasm from the
      giant axon of the marine invertebrate Myxicola infundibulum by photolytically
      releasing calcium from 'caged' compounds, while monitoring free calcium, [Ca2+],
      with Ca-sensing electrodes. In cytoplasm containing intact organelles, two
      features of the [Ca2+] response were seen upon light exposure: an initial spike
      from basal [Ca2+], followed by a slower phase recovery. Both the amplitude of the
      spike in [Ca2+] and the recovery were reduced by removal of MgATP. If organelles
      were removed from the cytoplasm, light exposure caused only a step-like change in
      [Ca2+] with no recovery. Apparent buffer capacities (delta bound Ca/delta free
      Ca) were unaffected by changing pH from 7.0 to 7.5; however, raising basal free
      calcium above 3 microM significantly reduced this parameter. The buffer capacity
      measured after the initial spike varied by as much as an order of magnitude from
      one giant axon to another but averaged approximately 50 in the absence and
      approximately 100 in the presence of 1 mM MgATP for [Ca2+] below 3 microM.

PMID- 8521456
TI  - Calcium diffusion coefficient in Myxicola axoplasm.
AB  - Calcium diffusion coefficients were measured in Myxicola axoplasm and in agar
      controls by two independent techniques: one utilizing 45Ca, and one utilizing Ca
      specific mini-electrodes. The lowest value, approximately 0.1 x 10(-6) cm2.s-1,
      was measured, using the mini-electrode technique, in axoplasm with intact Ca
      sequestering organelles. With ATP-depleted axoplasm, diffusion coefficients of
      0.5-2 x 10(-6) cm2.s-1 were obtained by both isotope and mini-electrode
      techniques. In organelle-free axoplasm with a protein concentration roughly half
      that in the intact axoplasm, diffusion coefficients of 1.4-3 x 10(-6) cm2.s-1
      were measured at 0.7 microM Ca and 7 x 10(-6) cm2.s-1 at 3-5 microM Ca. When
      compared with measurements of the calcium buffering capacity [Al-Baldawi NF.
      Abercrombie RF. (1995) Cytoplasmic Ca buffer capacity determined with Nitr-5 and
      DM-nitrophen. Cell Calcium, 17, 409-422], these diffusion coefficients require
      that part of the buffer capacity be located on mobile Ca-binding sites.

PMID- 8521457
TI  - Calcium pools in Ehrlich carcinoma cells. A major, high affinity Ca2+ pool is
      sensitive to both inositol 1,4,5-trisphosphate and thapsigargin.
AB  - To investigate the presence and the size of different non-mitochondrial Ca2+
      pools of Ehrlich ascites tumor cells (EATCs), digitonin-permeabilized cells were
      allowed to accumulate Ca2+ in the presence of mitochondrial inhibitors and
      treated with the reticular Ca(2+)-ATPase inhibitor thapsigargin, IP3 and the Ca2+
      ionophore A23187. Emptying of thapsigargin-sensitive Ca2+ stores prevented any
      Ca2+ release by IP3, and, after IP3 addition, little or no Ca2+ was released by
      thapsigargin. In both instances, a further Ca2+ release was accomplished by
      A23187. The IP3-thapsigargin-sensitive pool and the residual A23187-sensitive one
      corresponded to approximately 60 and 37% of non-mitochondrial stored Ca2+,
      respectively. In intact EATCs, IP3-dependent agonists and thapsigargin discharged
      Ca2+ pools almost completely overlapping, and A32187 released a minor residual
      Ca2+ pool. The IP3-insensitive pool appeared to have a relatively low affinity
      for Ca2+ (below 600 nM). The high affinity, IP3-sensitive Ca2+ pool was
      discharged in a 'quantal' manner following step additions of sub maximal [IP3],
      and the IP3-induced fractional Ca2+ release was more marked at higher
      concentrations of stored (luminal) Ca2+, The IP3-sensitive Ca2+ pool appeared to
      be devoid of the Ca(2+)-activated Ca2+ release channel since caffeine did not
      released any Ca2+ in intact and permeabilized EATCs, and Western blot analyses of
      EATC microsomal membranes failed to detect any known ryanodine receptor isoform.

PMID- 8521458
TI  - Stimulation of platelet-activating factor (PAF) receptors increases inositol
      phosphate production and cytosolic free Ca2+ concentrations in N1E-115
      neuroblastoma cells.
AB  - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine,
      PAF) has recently been recognized as an important mediator in the pathophysiology
      of brain injury. This study demonstrates that, in suspended populations of N1E
      115 cells loaded with Indo-1, biologically relevant concentrations of PAF produce
      a rapid and transient elevation in cytosolic free calcium concentration
      ([Ca2+]i). Moreover, nanomolar concentrations of PAF increase [3H]-inositol
      phosphate production. Using lyso-PAF and the specific PAF-receptor antagonists
      BN52021 and BN50739, we show that these effects were mediated by stimulation of
      PAF receptors. Experiments performed in Ca2+ free medium show that PAF-induced
      [Ca2+]i increase is the result of an influx of Ca2+ and of the release of
      intracellular Ca2+ stores. Studies of Mn2+ influx argue in favour of additional
      pathways for the PAF-induced Ca2+ influx other than the pathway for the
      thapsigargin-induced Ca2+ influx. Using the whole-cell voltage-clamp technique,
      we observe that PAF induces an increase of Ltype Ca2+ current. However, the
      effects of La3+, nifedipine and KCl-induced depolarization on the PAF-induced
      [Ca2+]i increase suggest a minor participation of these voltage-gated Ca2+
      channels in the response to PAF. Altogether the results point to the existence of
      a PAF-induced Ca2+ influx through receptor-operated Ca2+ permeant channels.

PMID- 8521459
TI  - IP3-mediated cytosolic and nuclear calcium elevation in NRK-52E cells using
      'caged' GPIP2.
AB  - Alterations in calcium homeostasis play a pivotal role in the cellular response
      to injury. Increases in the concentration of cytosolic free calcium ([Ca2+]i)
      result in a variety of calcium mediated toxic responses such as cytoskeletal
      alterations, mitochondrial damage, and over-expression of gene products. Inositol
      trisphosphate is a second messenger that links external cell surface signals to
      [Ca2+]i elevation. The present study explored the use of caged glycerophosphoryl
      myo-inositol-1,4,5-bisphosphate (GPIP2) to mediate a rapid and prolonged increase
      in [Ca2+]i in a normal rat kidney epithelial cell line (NRK-52E). In intact NRK
      52E cells, UV photolysis of microinjected GPIP2 resulted in a 3-4-fold sustained
      increase in [Ca2+]i. Graded photolytic release of GPIP2 also resulted in calcium
      mediated morphologic alterations, as shown by confocal microscopy, with cellular
      blebs apparent within 30 min. There was no apparent increase in [Ca2+]i or
      morphologic alterations in control cells microinjected with calcium indicator and
      equally exposed to UV light. Subsequent application of thapsigargin or ionomycin
      (1.0 microM) produced a rapid and transient increase in [Ca2+]i. In addition, we
      show that activation of IP3 stores results in increased concentration of ionized
      nuclear calcium, ([Ca2+]n) which persists longer than the increase in [Ca2+]i.
      These findings indicate that GPIP2 mediates a rapid and sustained elevation in
      [Ca2+]n and [Ca2+]i and this IP3-mediated calcium elevation is translated to the
      nucleus in rat kidney epithelial cells.

PMID- 8521460
TI  - Signal transduction of adipokinetic hormones involves Ca2+ fluxes and depends on
      extracellular Ca2+ to potentiate cAMP-induced activation of glycogen
      phosphorylase.
AB  - Adipokinetic hormone (AKH)-induced mobilization of insect fat body glycogen
      occurs through activation of glycogen phosphorylase. In the migratory locust,
      signal transduction of AKH-I, -II and -III has been shown to involve the
      formation of cAMP. In the present study, we show that both the elevation of fat
      body cAMP levels and the activation of phosphorylase by the three AKHs in vitro
      depend on the presence of extracellular Ca2+; in the absence of Ca2+ in the
      medium, no phosphorylase activation occurs, whereas a concentration of at least
      1.5 mM Ca2+ in the medium is required for maximal activation by each of the
      hormones. Furthermore, we show that AKH-I, -II and -III increase the influx of
      extracellular calcium into the fat body, as well as the efflux of cytosolic
      calcium from the fat body into the medium within 1 min of incubation. Although
      the time courses of their effects and the maximal responses to massive doses (40
      nM) of the three hormones do not differ, AKH-III induces the highest increase in
      Ca2+ efflux when applied in a physiological dose (4 nM). No difference in the
      levels of Ca2+ influx induced by 4 nM of the hormones was observed. Quantitative
      analysis of the data suggests that the AKH-induced influx is larger than the
      efflux, implying a net rise in the fat body Ca2+ concentration.

PMID- 8521461
TI  - Yes, but do they still get headaches?

PMID- 8521462
TI  - Unraveling chemosensory diversity.

PMID- 8521463
TI  - Cell-cell signaling, microtubules, and the loss of symmetry in the Drosophila
      oocyte.

PMID- 8521464
TI  - Regulation of growth factor activation by proteoglycans: what is the role of the
      low affinity receptors?

PMID- 8521465
TI  - New models in vogue for circadian clocks.

PMID- 8521466
TI  - Three-dimensional structure of E. coli core RNA polymerase: promoter binding and
      elongation conformations of the enzyme.
AB  - The structure of E. coli core RNA polymerase (RNAP) has been determined to
      approximately 23 A resolution by three-dimensional reconstruction from electron
      micrographs of flattened helical crystals. The structure reveals extensive
      conformational changes when compared with the previously determined E. coli RNAP
      holoenzyme structure, but resembles the yeast RNAPII structure. While each of
      these structures contains a thumb-like projection surrounding a channel 25 A in
      diameter, the E. coli RNAP holoenzyme thumb defines a deep but open groove on the
      molecule, whereas the thumb of E. coli core and yeast RNAPII form part of a ring
      that surrounds the channel. This may define promoter-binding and elongation
      conformations of RNAP, as E. coli holoenzyme recognizes promoter sites on double
      stranded DNA, while both E. coli core and yeast RNAPII are elongating forms of
      the polymerase and are incapable of promoter recognition.

PMID- 8521467
TI  - Assembly of phage Mu transpososomes: cooperative transitions assisted by protein
      and DNA scaffolds.
AB  - Transposition of phage Mu takes place within higher order protein-DNA complexes
      called transpososomes. These complexes contain the two Mu genome ends synapsed by
      a tetramer of Mu transposase (MuA). Transpososome assembly is tightly controlled
      by multiple protein and DNA sequence cofactors. We find that assembly can occur
      through two distinct pathways. One previously described pathway depends on an
      enhancer-like sequence element, the internal activation sequence (IAS). The
      second pathway depends on a MuB protein-target DNA complex. For both pathways,
      all four MuA monomers in the tetramer need to interact with an assembly-assisting
      element, either the IAS or MuB. However, once assembled, not all MuA monomers
      within the transpososome need to interact with MuB to capture MuB-bound target
      DNA. The multiple layers of control likely are used in vivo to ensure efficient
      rounds of DNA replication when needed, while minimizing unwanted transposition
      products.

PMID- 8521468
TI  - Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and
      occurs in two steps.
AB  - Formation of double-strand breaks at recombination signal sequences is an early
      step in V(D)J recombination. Here we show that purified RAG1 and RAG2 proteins
      are sufficient to carry out this reaction. The cleavage reaction can be divided
      into two distinct steps. First, a nick is introduced at the 5' end of the signal
      sequence. The other strand is then broken, resulting in a hairpin structure at
      the coding end and a blunt, 5'-phosphorylated signal end. The hairpin is made as
      a direct consequence of the cleavage mechanism. Nicking and hairpin formation
      each require the presence of a signal sequence and both RAG proteins.

PMID- 8521469
TI  - p65cdc18 plays a major role controlling the initiation of DNA replication in
      fission yeast.
AB  - A key problem in the cell cycle is understanding what brings about the initiation
      of DNA replication and how this is linked with global cell cycle controls. The
      fission yeast gene cdc18 is required for DNA replication and is transcriptionally
      activated by the cdc10/res1/res2 control acting at START in late G1. We show here
      that overexpressing cdc18 is able to bring about repeated rounds of DNA synthesis
      in the absence of mitosis and of continuing protein synthesis. The level of the
      cdc18-encoded protein p65cdc18 is periodic in the cell cycle, peaking at the G1
      to S phase transition, and p65cdc18 is located in the nucleus when cdc18 is
      overexpressed. We propose that p65cdc18 acts at the initiation of DNA replication
      and plays a major role in controlling the onset of S phase.

PMID- 8521470
TI  - The genetic basis for specific anosmia to isovaleric acid in the mouse.
AB  - The detection and discrimination of odorants in mammals is thought to be mediated
      by a family of 100-1000 seven transmembrane domain receptor proteins, although
      none of these putative olfactory receptors have been shown to bind individual
      odorants with high affinity. We have used a genetic approach to identify the
      genomic regions responsible for the differential ability of two inbred mouse
      strains to detect a single odorant, isovaleric acid. Results obtained with a
      behavioral assay were consistent with a limited number of genes conferring the
      ability to detect isovaleric acid. One genetic location mapped to a 0.3 cM region
      between D4MIT37 and D4MIT156 on mouse chromosome 4. A second locus mapped to the
      distal end of mouse chromosome 6. The most likely cause of the behavior
      difference between the two strains of mice is the loss of the receptor protein or
      proteins responsible for recognizing isovaleric acid. High resolution genetic
      mapping provides a novel approach to the identification of genes critical for the
      detection of particular odorants.

PMID- 8521471
TI  - A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent
      nuclear protein export pathway.
AB  - Pre-mRNAs are associated with hnRNPs, and these proteins play important roles in
      the biogenesis of mRNAs. The hnRNP A1 is one of the most abundant hnRNPs, and
      although localized primarily in the nucleoplasm, shuttles continuously between
      the nucleus and the cytoplasm. A 38 amino acid domain within A1, termed M9, which
      bears no resemblance to classical nuclear localization signal (NLS) sequences,
      localizes A1 to the nucleus. Here we show that M9 is also a nuclear export
      signal; placing M9 on a protein that is otherwise restricted to the nucleus, the
      nucleoplasmin core domain (NPc), efficiently exports it to the cytoplasm in a
      temperature-dependent manner. In contrast, classical NLSs cannot promote the
      export of NPc. These findings demonstrate that there is a signal-dependent,
      temperature-sensitive nuclear export pathway and strengthen the suggestion that
      A1 and other shuttling hnRNPs function as carriers for RNA during export to the
      cytoplasm.

PMID- 8521472
TI  - Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane
      fusion.
AB  - We have identified a novel 100 kDa coiled-coil protein, rabaptin-5, that
      specifically interacts with the GTP form of the small GTPase Rab5, a potent
      regulator of endocytic transport. It is mainly cytosolic, but a fraction
      colocalizes with Rab5 to early endosomes. Expression of a GTPase-deficient Rab5
      mutant enhances the binding of rabaptin-5 to enlarged endosomes. Overexpression
      of rabaptin-5 alone is sufficient to promote expansion of early endosomes. Rab5
      recruits rabaptin-5 to purified early endosomes in a GTP-dependent manner,
      demonstrating functional similarities with other members of the Ras superfamily.
      Immunodepletion of rabaptin-5 from cytosol strongly inhibits Rab5-dependent early
      endosome fusion. Rabaptin-5 is thus a Rab effector required for membrane docking
      and fusion.

PMID- 8521473
TI  - Structure and function of the beta 2 subunit of brain sodium channels, a
      transmembrane glycoprotein with a CAM motif.
AB  - Voltage-gated sodium channels in brain neurons are complexes of a pore-forming
      alpha subunit with smaller beta 1 and beta 2 subunits. cDNA cloning and
      sequencing showed that the beta 2 subunit is a 186 residue glycoprotein with an
      extracellular NH2-terminal domain containing an immunoglobulin-like fold with
      similarity to the neural cell adhesion molecule (CAM) contactin, a single
      transmembrane segment, and a small intracellular domain. Coexpression of beta 2
      with alpha subunits in Xenopus oocytes increases functional expression, modulates
      gating, and causes up to a 4-fold increase in the capacitance of the oocyte,
      which results from an increase in the surface area of the plasma membrane
      microvilli. beta 2 subunits are unique among the auxiliary subunits of ion
      channels in combining channel modulation with a CAM motif and the ability to
      expand the cell membrane surface area. They may be important regulators of sodium
      channel expression and localization in neurons.

PMID- 8521474
TI  - Identification of domains conferring G protein regulation on inward rectifier
      potassium channels.
AB  - Cardiac m2 muscarinic acetylcholine receptors reduce heart rate by coupling to
      heterotrimeric (alpha beta gamma) guanine nucleotide-binding (G) proteins that
      activate IKACh, an inward rectifier K+ channel (IRK). Activation of the GIRK
      subunit of IKACh requires G beta gamma subunits; however, the structural basis of
      channel regulation is unknown. To determine which sequences confer G beta gamma
      regulation upon IRKs, we generated chimeric proteins composed of GIRK and RB
      IRK2, a related, G protein-insensitive channel. Importantly, a chimeric channel
      containing the hydrophobic pore region of RB-IRK2 joined to the amino and
      carboxyl termini of GIRK exhibited voltage- and receptor-dependent activation in
      Xenopus oocytes. Furthermore, carboxy-terminal sequences specific to this chimera
      and GIRK bound G beta gamma subunits in vitro. Thus, G beta gamma may regulate
      IRKs by interacting with sequences adjacent to the putative channel pore.

PMID- 8521475
TI  - hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial
      cell sheet movement.
AB  - During Drosophila embryogenesis, a cell sheet movement, dorsal closure, allows
      establishment of the dorsal epidermis. In this morphogenetic process, lateral
      epithelia undergo a dramatic movement toward the dorsal midline. In the mutant
      hemipterous (hep), spreading of the epithelia is blocked; in genetically
      sensitized hep embryos, cell sheet movement can be arrested at any time,
      indicating hep requirement in maintaining this morphogenetic activity. Further,
      hep is required for expression in the dorsal epithelium edges of another dorsal
      closure gene, puckered. The HEP protein is homologous to the Jun kinase kinase
      (JNKK) group of mitogen-activated protein kinase kinases (MAPKKs). These data
      suggest that hep functions in a novel Drosophila MAPK pathway, controlling
      puckered expression and morphogenetic activity of the dorsal epidermis.

PMID- 8521476
TI  - Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12
      complex modulates Ca2+ flux.
AB  - The immunosuppressant drug FK506 binds to the immunophilin protein FKBP12 and
      inhibits its prolyl isomerase activity. Immunosuppressive actions, however, are
      mediated via an FK506-FKBP12 inhibition of the Ca(2+)-activated phosphatase
      calcineurin. Physiologic cellular roles for FKBP12 have remained unclear. FKBP12
      is physically associated with the RyR and IP3R Ca2+ channels in the absence of
      FK506, with added FK506 disrupting these complexes. Dissociation of FKBP12
      results in alteration of channel Ca2+ conductance in both cases. We now report
      that calcineurin is physiologically associated with the IP3R-FKBP12 and RyR
      FKBP12 receptor complexes and that this interaction can be disrupted by FK506 or
      rapamycin. Calcineurin anchored to the IP3R via FKBP12 regulates the
      phosphorylation status of the receptor, resulting in a dynamic Ca(2+)-sensitive
      regulation of IP3-mediated Ca2+ flux.

PMID- 8521477
TI  - Prostaglandin synthase 2 gene disruption causes severe renal pathology in the
      mouse.
AB  - The prostaglandin endoperoxide H synthase isoform 2, cyclooxygenase 2 (COX-2), is
      induced at high levels in migratory and other responding cells by pro
      inflammatory stimuli. COX-2 is generally considered to be a mediator of
      inflammation. Its isoform, COX-1, is constitutively expressed in most tissues and
      is thought to mediate "housekeeping" functions. These two enzymes are therapeutic
      targets of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs). To
      investigate further the different physiologic roles of these isoforms, we have
      used homologous recombination to disrupt the mouse gene encoding COX-2 (Ptgs2).
      Mice lacking COX-2 have normal inflammatory responses to treatments with
      tetradecanoyl phorbol acetate or with arachidonic acid. However, they develop
      severe nephropathy and are susceptible to peritonitis.

PMID- 8521478
TI  - Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced
      inflammation and indomethacin-induced gastric ulceration.
AB  - Cyclooxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin
      biosynthesis and the target enzymes for the widely used nonsteroidal anti
      inflammatory drugs. To study the physiological roles of the individual isoforms,
      we have disrupted the mouse Ptgs1 gene encoding COX-1. Homozygous Ptgs1 mutant
      mice survive well, have no gastric pathology, and show less indomethacin-induced
      gastric ulceration than wild-type mice, even though their gastric prostaglandin
      E2 levels are about 1% of wild type. The homozygous mutant mice have reduced
      platelet aggregation and a decreased inflammatory response to arachidonic acid,
      but not to tetradecanoyl phorbol acetate. Ptgs1 homozygous mutant females mated
      to homozygous mutant males produce few live offspring. COX-1-deficient mice
      provide a useful model to distinguish the physiological roles of COX-1 and COX-2.

PMID- 8521479
TI  - Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing
      prostaglandin endoperoxide synthase 2.
AB  - Prostaglandin endoperoxide synthase 2, also referred to as cyclooxygenase 2 (COX
      2), is a key enzyme in the conversion of arachidonic acid to prostaglandins and
      other eicosanoids. Rat intestinal epithelial (RIE) cells were permanently
      transfected with a COX-2 expression vector oriented in the sense (RIE-S) or
      antisense (RIE-AS) direction. The RIE-S cells expressed elevated COX-2 protein
      levels and demonstrated increased adhesion to extracellular matrix (ECM)
      proteins. E-cadherin was undetectable in RIE-S cells, but was elevated in
      parental RIE (RIE-P) and RIE-AS cells. RIE-S cells were resistant to butyrate
      induced apoptosis, had elevated BCL2 protein expression, and reduced transforming
      growth factor beta 2 receptor levels. The phenotypic changes involving both
      increased adhesion to ECM and inhibition of apoptosis were reversed by sulindac
      sulfide (a COX inhibitor). These studies demonstrate that overexpression of COX-2
      leads to phenotypic changes in intestinal epithelial cells that could enhance
      their tumorigenic potential.

PMID- 8521480
TI  - Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex.
AB  - The crystal structure of the snake toxin fasciculin, bound to mouse
      acetylcholinesterase (mAChE), at 3.2 A resolution reveals a synergistic three
      point anchorage consistent with the picomolar dissociation constant of the
      complex. Loop II of fasciculin contains a cluster of hydrophobic residues that
      interact with the peripheral anionic site of the enzyme and sterically occlude
      substrate access to the catalytic site. Loop I fits in a crevice near the lip of
      the gorge to maximize the surface area of contact of loop II at the gorge entry.
      The fasciculin core surrounds a protruding loop on the enzyme surface and
      stabilizes the whole assembly. Upon binding of fasciculin, subtle structural
      rearrangements of AChE occur that could explain the observed residual catalytic
      activity of the fasciculin-enzyme complex.

PMID- 8521481
TI  - Vesicle biogenesis: the coat connection.

PMID- 8521482
TI  - What the fly's glia tell the fly's brain.

PMID- 8521483
TI  - The elemental principles of calcium signaling.

PMID- 8521484
TI  - Calcium ions as extracellular messengers.

PMID- 8521485
TI  - Protein import into nuclei: association and dissociation reactions involving
      transport substrate, transport factors, and nucleoporins.
AB  - The molecular dynamics of nuclear protein import were examined in a solution
      binding assay by testing for interactions between a protein containing a nuclear
      localization signal (NLS), the transport factors karyopherin alpha, karyopherin
      beta, and Ran, and FXFG or GLFG repeat regions of nucleoporins. We found that
      karyopherins alpha and beta cooperate to bind FXFG but not GLFG repeat regions.
      Binding of the NLS protein to karyopherin alpha was enhanced by karyopherin beta.
      Two novel reactions were discovered. First, incubation of a karyopherin
      heterodimer-NLS protein complex with an FXFG repeat region stimulated the
      dissociation of the NLS protein from the karyopherin heterodimer. Second,
      incubation of the karyopherin heterodimer with RanGTP (or with a Ran mutant that
      cannot hydrolyze GTP) led to the dissociation of karyopherin alpha from beta and
      to an association of Ran with karyopherin beta; RanGDP had no effect. We propose
      that movement of NLS proteins across the nuclear pore complex is a stochastic
      process that operates via repeated association-dissociation reactions.

PMID- 8521486
TI  - Axon membrane flows from the growth cone to the cell body.
AB  - During the growth of axons, the surface area of the neuron increases
      dramatically. Membrane addition as well as exchange could contribute to rapid
      membrane dynamics or flow. Using diffusing latex beads to monitor membrane flow,
      we find that axonal membrane flows rapidly (7 microns/min) from growth cone to
      cell body during axon growth and that flow is inhibited by brefeldin A. To power
      this flow, there is a membrane lesion gradient from growth cone to cell body that
      could draw the membrane over the axon at that rate. Further, when an artificial
      flow is induced to the center of the axon by use of laser tweezers, the primary
      source of the membrane is from the growth cone. We suggest that during neuron
      growth, there is excess membrane added at the growth cone in chick dorsal ganglia
      (DRGs) that undergoes edcocytosis at the cell body, thereby creating a flow that
      can rapidly alter the content of the axon membrane.

PMID- 8521487
TI  - Cytoplasmic coat proteins involved in endosome function.
AB  - Endosomes are intermediates for a complex series of sorting and transport events
      that occur during receptor-mediated endocytosis. These involve the recognition of
      targeting determinants on the cytoplasmic domains of many membrane proteins as
      well as the formations of specific transport vesicles. Accordingly, endosome
      function is likely to be governed by the regulated assembly of cytoplasmic coat
      complexes. We have found that, in vitro, endosomes recruit a characteristic set
      of cytoplasmic proteins in a GTP gamma S-stimulated and brefeldin A-sensitive
      fashion. Among these are members of the COP-I and ARF families of coat proteins.
      In addition, endosomes were also found to assemble distinct, clathrin-like coats.
      Since microinjection of antibodies to beta-COP inhibits the entry of enveloped
      viruses via the endocytic pathway, it is apparent that the recruitment of COP-I
      or COP-I-related proteins plays an important role in the function of endosomes in
      intact cells.

PMID- 8521488
TI  - Integrin activation and cytoskeletal interaction are essential for the assembly
      of a fibronectin matrix.
AB  - Fibronectin (Fn) matrices are vital to vertebrate development and wound healing
      and modulate tumorigenesis. We used a recombinant Fn-binding integrin alpha IIb
      beta3, to define rules for integrin-initiated Fn matrix formation. We report the
      following. First, multiple Fn-binding integrins can support matrix assembly;
      their activation state controls fibrillogenesis. Second, Fn binding to cells
      expressing an activated integrin is necessary but not sufficient for matrix
      assembly. Additional "postoccupancy" events involving the integrin beta, but not
      the alpha subunit, cytoplasmic domain are needed. Third, these postoccupancy
      events require an intact actin cytoskeleton. We propose a model for integrin
      involvement in Fn fibrillogenesis that reconciles previous paradoxes and suggests
      novel approaches to the therapeutic control of Fn matrix assembly.

PMID- 8521489
TI  - Epigenetic control of an endogenous gene family is revealed by a novel blue
      fluorescent mutant of Arabidopsis.
AB  - The Wassilewskija strain of Arabidopsis has four genes encoding the tryptophan
      enzyme phosphoribosylanthranilate isomerase (PAI) located at three unlinked
      sites. These four PAI genes are methylated over their regions of DNA homology.
      When PAI copy number is reduced by deletion of two tandemly arrayed genes (MePAI1
      PAI4), a mutant with fluorescent, tryptophan-deficient phenotypes results,
      because the two remaining methylated PAI genes (MePAI2 and MePAI3) supply
      insufficient PAI activity. These two methylated genes can be inherited through
      meiosis, even when they are segregated away from each other in crosses to a
      strain with unmethylated PAI genes. However, the mutant phenotypes conferred by
      the methylated PAI genes are unstable, and mutant plants yield occasional
      revertant somatic sectors and progeny. Revertant lines display coordinately
      reduced methylation of both PAI2 and PAI3, implying that this hypomethylation
      acts in a concerted manner across the genome rather than at individual sites.

PMID- 8521490
TI  - The BELL1 gene encodes a homeodomain protein involved in pattern formation in the
      Arabidopsis ovule primordium.
AB  - Ovule development in Arabidopsis involves the formation of three morphologically
      defined proximal-distal pattern elements. Integuments arise from the central
      pattern element. Analysis of Bell 1 (Bel 1) mutant ovules indicated that BEL1 was
      required for integument development. Cloning of the BEL1 locus reveals that it
      encodes a homeodomain transcription factor. Prior to integument initiation, BEL1
      RNA localizes to the central domain, providing molecular evidence for a central
      pattern element. Therefore, proximal-distal patterning of the ovule involves the
      regulated expression of the BEL1 gene that controls integument morphogenesis. A
      model for BEL1 function is evaluated with regard to new data showing the
      expression pattern of the floral homeotic gene AGAMOUS (AG) early in wild-type
      and BEL1 ovule development.

PMID- 8521491
TI  - Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle
      alignment in early C. elegans embryos.
AB  - The par-3 gene is required for establishing polarity in early C. elegans embryos.
      Embryos from par-3 homozygous mothers show defects in segregation of cytoplasmic
      determinants and in positioning of the early cleavage spindles. We report here
      that the PAR-3 protein is asymmetrically distributed at the periphery of the
      zygote and asymmetrically dividing blastomeres of the germline lineage. The PAR-3
      distribution is roughly the reciprocal of PAR-1, another protein required for
      establishing embryonic polarity in C. elegans. Analysis of the distribution of
      PAR-3 and PAR-1 in other par mutants reveals that par-2 activity is required for
      proper localization of PAR-3 and that PAR-3 is required for proper localization
      of PAR-1. In addition, the distribution of the PAR-3 protein correlates with
      differences in cleavage spindle orientation and suggests a mechanism by which PAR
      3 contributes to control of cleavage pattern.

PMID- 8521492
TI  - JUN cooperates with the ETS domain protein pointed to induce photoreceptor R7
      fate in the Drosophila eye.
AB  - R7 photoreceptor fate in the Drosophila eye induced by the activation of the
      Sevenless receptor tyrosine kinase and the RAS/MAP kinase signal transduction
      pathway. We show that expression of a constitutively activated JUN isoform in
      ommatidial precursor cells is sufficient to induce R7 fate independent of
      upstream signals normally required for photoreceptor determination. We present
      evidence that JUN interacts with the ETS domain protein Pointed to promote R7
      formation. This interaction is cooperative when both proteins are targeted to the
      same promoter and is antagonized by another ETS domain protein, YAN, a negative
      regulator of R7 development. Furthermore, phyllopod, a putative transcriptional
      target of RAS pathway activation during R7 induction, behaves as a suppressor of
      activated JUN. Taken together, these data suggest that JUN and Pointed act on
      common target genes to promote neuronal differentiation in the Drosophila eye,
      and that phyllopod might be such a common target.

PMID- 8521493
TI  - The solution structure of the human ETS1-DNA complex reveals a novel mode of
      binding and true side chain intercalation.
AB  - The solution structure of a 24.4 kDa specific complex of the DNA-binding domain
      (DBD) of the human ETS1 (hETS1) oncoprotein with a 17-mer DNA has been solved by
      NMR. The interaction of the hETS1 DBD with DNA reveals a surprising twist on the
      general features of helix-turn-helix (HTH)-DNA interactions. Major groove
      recognition involves the C-terminal two thirds of the HTH recognition helix,
      while minor groove recognition occurs via true intercalation of the side chain of
      Trp-28, which extends from the minor to the major groove. This results in a sharp
      kink of approximately 60 degrees and a widening of the minor groove over one-half
      turn of the DNA. The orientation of the HTH element of the hETS1 DBD with respect
      to the major groove is significantly rotated relative to other HTH proteins.
      These observations establish the ETS family of DNA-binding proteins as a distinct
      family of HTH proteins.

PMID- 8521494
TI  - Atomic model of a pyrimidine dimer excision repair enzyme complexed with a DNA
      substrate: structural basis for damaged DNA recognition.
AB  - T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 that catalyzes the
      first reaction step of the pyrimidine dimer-specific base excision repair
      pathway. The crystal structure of this enzyme complexed with a duplex DNA
      substrate, containing a thymine dimer, has been determined at 2.75 A resolution.
      The atomic structure of the complex reveals the unique conformation of the DNA
      duplex, which exhibits a sharp kink with a 60 degree inclination at the central
      thymine dimer. The adenine base complementary to the 5' side of the thymine dimer
      is completely flipped out of the DNA duplex and trapped in a cavity on the
      protein surface. These structural features allow an understanding of the
      catalytic mechanism and implicate a general mechanism of how other repair enzymes
      recognize damaged DNA duplexes.

PMID- 8521495
TI  - Identification of double Holliday junctions as intermediates in meiotic
      recombination.
AB  - During meiosis, branched DNA molecules containing information from both parental
      chromosomes occur in vivo at loci where meiosis-specific double-stranded breaks
      occur. We demonstrate here that these joint molecules are recombination
      intermediates: they contain single strands that have undergone exchange of
      information. Moreover, these joint molecules are resolved into both parental and
      recombinant duplexes when treated in vitro with Holliday junction-resolving
      endonucleases RuvC or T4 endo VII. Taken together with previous observations,
      these results strongly suggest that joint molecules are double Holliday
      junctions.

PMID- 8521496
TI  - The transmembrane form of tumor necrosis factor is the prime activating ligand of
      the 80 kDa tumor necrosis factor receptor.
AB  - The 60 kDa tumor necrosis factor receptor (TNFR60) is regarded as the major
      signal transducer of TNF-induced cellular responses, whereas the signal capacity
      and role of the 80 kDa TNFR (TNFR80) remain largely undefined. We show here that
      the transmembrane form of TNF is superior to soluble TNF in activating TNFR80 in
      various systems such as T cell activation, thymocyte proliferation, and
      granulocyte/macrophage colony-stimulating factor production. Intriguingly,
      activation of TNFR80 by membrane TNF can lead to qualitatively different TNF
      responses such as rendering resistant tumor cells sensitive to TNF-mediated
      cytotoxicity. This study demonstrates that the diversity of TNF effects can be
      controlled through the differential sensitivity of TNFR80 for the two forms of
      TNF and suggests an important physiological role for TNFR80 in local inflammatory
      responses.

PMID- 8521497
TI  - 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte
      determination factor PPAR gamma.
AB  - Regulation of adipose cell mass is a critical homeostatic process in higher
      vertebrates. The conversion of fibroblasts into cells of the adipose lineage is
      induced by expression of the orphan nuclear receptor PPAR gamma. This suggests
      that an endogenous PPAR gamma ligand may be an important regulator of
      adipogenesis. By assaying arachidonate metabolites for their capacity to activate
      PPAR response elements, we have identified 15-deoxy-delta 12, 14-prostaglandin J2
      as both a PPAR gamma ligand and an inducer of adipogenesis. Similarly, the
      thiazolidinedione class of antidiabetic drugs also bind to PPAR gamma and act as
      potent regulators of adipocyte development. Thus, adipogenic prostanoids and
      antidiabetic thiazolidinediones initiate key transcriptional events through a
      common nuclear receptor signaling pathway. These findings suggest a pivotal role
      for PPAR gamma and its endogenous ligand in adipocyte development and glucose
      homeostasis and as a target for intervention in metabolic disorders.

PMID- 8521498
TI  - A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor
      gamma and promotes adipocyte differentiation.
AB  - Prostaglandins (PGs) of the J2 series form in vivo and exert effects on a variety
      of biological processes. While most of PGs mediate their effects through G
      protein-coupled receptors, the mechanism of action for the J2 series of PGs
      remains unclear. Here, we report the PGJ2 and its derivatives are efficacious
      activators of peroxisome proliferator-activated receptors alpha and gamma (PPAR
      alpha and PPAR gamma, respectively), orphan nuclear receptors implicated in lipid
      homeostasis and adipocyte differentiation. The PGJ2 metabolite 15-deoxy-delta
      12,14-PGJ2 binds directly to PPAR gamma and promotes efficient differentiation of
      C3H10T1/2 fibroblasts to adipocytes. These data provide strong evidence that a
      fatty acid metabolite can function as an adipogenic agent through direct
      interactions with PPAR gamma and furthermore, suggest a novel mechanism of action
      for PGs of the J2 series.

PMID- 8521499
TI  - Phosphatidylinositol (3,4,5)P3 interacts with SH2 domains and modulates PI 3
      kinase association with tyrosine-phosphorylated proteins.
AB  - Src homology 2 (SH2) domains on the regulatory subunit of phosphoinositide 3
      kinase (PI 3-kinase) mediate its binding to specific tyrosine-phosphorylated
      proteins in stimulated cells. Using a pharmacological and genetic approach, we
      show that the amount of PI 3-kinase associated with tyrosine-phosphorylated
      proteins inversely correlates with the amount of PI 3-kinase lipid products
      present in the cell. An explanation for this observation is provided by our
      finding that phosphatidylinositol (3,4,5)trisphosphate (Ptdlns [3,4,5]P3) binds
      directly and selectively to the SH2 domains of the 85 kDa subunit of PI 3-kinase
      and thereby blocks binding to tyrosine-phosphorylated proteins. The SH2 domain of
      pp60C-STC also specifically bound Ptdlns (3,4,5)P3, and the binding was competed
      by a phosphopeptide specific for the Src SH2 domain. These results indicate that
      production of Ptdlns (3,4,5)P3 at the membrane disrupts the binding of PI 3
      kinase to phosphoproteins. This lipid may also recruit other SH2-containing
      proteins to the membrane to initiate downstream signaling.

PMID- 8521500
TI  - p25rum1 orders S phase and mitosis by acting as an inhibitor of the p34cdc2
      mitotic kinase.
AB  - p25rum1 from the fission yeast S. pombe is shown to act as a specific in vitro
      inhibitor of the p34cdc2/p56cdc13 mitotic kinase. It is also shown that early G1
      cells contain p25rum1, which associates with and inhibits the mitotic kinase, and
      maintains p56cdc13 mitotic B cyclin at a low level, ensuring that these cells do
      not undergo a premature lethal entry into mitosis. A high level of p25rum1 in G2
      cells inhibits the p34cdc2/p56cdc13 kinase that removes the block preventing a
      further S phase and leads to repeated rounds of DNA replication. Thus, the cyclin
      dependent kinase inhibitor p25rum1, acting on the p34cdc2 mitotic kinase, plays
      an important role in ensuring the correct sequence of S phase and mitosis during
      the cell cycle.

PMID- 8521501
TI  - Purification and properties of an ATP-dependent nucleosome remodeling factor.
AB  - We report the purification of an ATP-dependent nucleosome remodeling factor
      (NURF) from Drosophila embryo extracts. NURF is composed of at least four
      polypeptides that act in concert with the GAGA transcription factor to alter
      chromatin structure at the hsp70 promoter. The energy requirement is attributed
      to an ATPase activity that is stimulated by nucleosomes but not by free DNA or
      histones, suggesting that NURF acts directly on a nucleosome to perturb its
      structure. This finding and the physical properties of NURF contrast sharply with
      the multisubunit SWI2/SNF2 complex, which has also been shown to alter
      nucleosomes in an ATP-dependent manner. The results suggest that two distinct
      systems may be involved in remodeling chromatin for transcription.

PMID- 8521502
TI  - ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the
      nucleosome remodeling factor.
AB  - The generation of an accessible heat shock promoter in chromatin in vitro
      requires the concerted action of the GAGA transcription factor and NURF, an ATP
      dependent nucleosome remodeling factor. NURF is composed of four subunits and is
      biochemically distinct from the SWI2/SNF2 multiprotein complex, a transcriptional
      activator that also appears to alter nucleosome structure. We have obtained
      protein microsequence and immunological evidence identifying the 140 kDa subunit
      of NURF as ISWI, previously of unknown function but highly related to SWI2/SNF2
      only in the ATPase domain. The ISWI protein is localized to the cell nucleus and
      is expressed throughout Drosophila development at levels as high as 100,000
      molecules/cell. The convergence of biochemical and genetic studies on ISWI and
      SWI2/SNF2 underscores these ATPases and their close relatives as key components
      of independent systems for chromatin remodeling.

PMID- 8521503
TI  - The global folding of four-way helical junctions in RNA, including that in U1
      snRNA.
AB  - Helical junctions are important elements in the architecture of folded RNA
      molecules. The global geometry of fully base-paired four-way junctions between
      RNA helices has been analyzed by comparative gel electrophoresis. Junctions
      appear to fold by pairwise coaxial helical stacking in one of two possible
      stereochemically equivalent isomers based upon alternative selections of stacking
      partners. In the presence of 1 mM Mg2+, the two continuous helical axes are
      approximately at right angles to each other for all junctions studied, but the
      RNA junctions exhibit significant sequence-dependent differences in their
      structures as a function of ionic conditions. The four-way junction found in the
      U1 snRNA folded by coaxial helical stacking. It retained the 90 degrees crossed
      stacked structure under all ionic conditions tested, despite the presence of a
      G.A mismatch at the point of strand exchange.

PMID- 8521504
TI  - Structure of the high affinity complex of inositol trisphosphate with a
      phospholipase C pleckstrin homology domain.
AB  - The X-ray crystal structure of the high affinity complex between the pleckstrin
      homology (PH) domain from rat phospholipase C-delta 1 (PLC-delta 1) and inositol
      (1,4,5)-trisphosphate (Ins(1,4,5)P3) has been refined to 1.9 A resolution. The
      domain fold is similar to others of known structure. Ins(1,4,5)P3 binds on the
      positively charged face of the electrostatically polarized domain, interacting
      predominantly with the beta 1/beta 2 and beta 3/beta 4 loops. The 4- and 5
      phosphate groups of Ins(1,4,5)P3 interact much more extensively than the 1
      phosphate. Two amino acids in the PLC-delta 1 PH domain that contact Ins(1,4,5)P3
      have counterparts in the Bruton's tyrosine kinase (Btk) PH domain, where
      mutational changes cause inherited agammaglobulinemia, suggesting a mechanism for
      loss of function in Btk mutants. Using electrostatics and varying levels of head
      group specificity, PH domains may localize and orient signaling proteins,
      providing a general membrane targeting and regulatory function.

PMID- 8521505
TI  - The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2.
AB  - The crystallographic structure of the G protein heterotrimer Gi alpha 1(GDP)beta
      1 gamma 2 (at 2.3 A) reveals two nonoverlapping regions of contact between alpha
      and beta, an extended interface between beta and nearly all of gamma, and limited
      interaction of alpha with gamma. The major alpha/beta interface covers switch II
      of alpha, and GTP-induced rearrangement of switch II causes subunit dissociation
      during signaling. Alterations in GDP binding in the heterotrimer (compared with
      alpha-GDP) explain stabilization of the inactive conformation of alpha by beta
      gamma. Repeated WD motifs in beta form a circularized sevenfold beta propeller.
      The conserved cores of these motifs are a scaffold for display of their more
      variable linkers on the exterior face of each propeller blade.

PMID- 8521506
TI  - KSR: a novel player in the RAS pathway.

PMID- 8521507
TI  - The nuclear receptor superfamily: the second decade.

PMID- 8521508
TI  - The RXR heterodimers and orphan receptors.

PMID- 8521509
TI  - Steroid hormone receptors: many actors in search of a plot.

PMID- 8521510
TI  - Nonsteroid nuclear receptors: what are genetic studies telling us about their
      role in real life?

PMID- 8521511
TI  - From embryogenesis to metamorphosis: the regulation and function of Drosophila
      nuclear receptor superfamily members.

PMID- 8521512
TI  - KSR, a novel protein kinase required for RAS signal transduction.
AB  - We have identified and characterized two genes in Drosophila whose products are
      required for activated RAS to signal with normal efficiency, but do not appear to
      effect signaling by activated RAF. One encodes the beta subunit of type I
      geranylgeranyl transferase, a prenylation enzyme essential for targeting RAS to
      the plasma membrane. The other encodes a protein kinase that we have named kinase
      suppressor of ras (ksr). By genetic criteria, we show that KSR functions in
      multiple receptor tyrosine kinase pathways. We have isolated mammalian homologs
      of KSR that, together with the Drosophila gene, define a novel class of kinases.
      Our results suggest that KSR is a general and evolutionarily conserved component
      of the RAS signaling pathway that acts between RAS and RAF.

PMID- 8521513
TI  - The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras
      mediated signal transduction.
AB  - Vulval induction in C. elegans is controlled by a highly conserved signaling
      pathway similar to the RTK-Ras-MAPK cascade in mammals. By screening for
      suppressors of the Multivulva phenotype caused by an activated let-60 ras allele,
      we isolated mutations in a gene, ksr-1, that acts as a positive modifier of
      vulval induction and is required for at least two other let-60 ras-mediated
      processes. Although ksr-1 mutations do not perturb vulval induction in an
      otherwise wild-type background, they have very strong effects on vulval induction
      in genetic backgrounds where Ras pathway activity is constitutively activated or
      compromised, suggesting that ksr-1 activity is required for maximal stimulation
      of vulval fates by the Ras pathway. Genetic epistasis analysis suggests that ksr
      1 acts downstream of or in parallel to let-60 ras. We cloned ksr-1 and have shown
      that it encodes a novel putative protein kinase related to the Raf family of
      Ser/Thr kinases.

PMID- 8521514
TI  - The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling
      in C. elegans.
AB  - By screening for mutations that suppress the vulval defects caused by a
      constitutively active let-60 ras gene, we identified six loss-of-function alleles
      of ksr-1, a novel C. elegans gene. Our genetic analysis showed ksr-1 positively
      mediates Ras signaling and functions downstream of or in parallel to let-60. In
      the absence of ksr-1 function, normal Ras signaling is impaired only slightly,
      suggesting ksr-1 may act to modulate, or in a branch that diverges from, the main
      signaling pathway. The predicted KSR-1 protein has a protein kinase domain and is
      most similar to a recently identified Drosophila protein involved in Ras
      signaling. We propose that the function of ksr-1 is evolutionarily conserved.

PMID- 8521515
TI  - Coronin involved in phagocytosis: dynamics of particle-induced relocalization
      visualized by a green fluorescent protein Tag.
AB  - Coronin is a protein involved in cell locomotion and cytokinesis of Dictyostelium
      discoideum. Here we show that coronin is strongly enriched in phagocytic cups
      formed in response to particle attachment. A fusion of coronin with green
      fluorescent protein (GFP) accumulates in the cups within less than 1 min upon
      attachment of a particle and is gradually released from the phagosome within 1
      min after engulfment is completed. Phagocytic cup formation competes with leading
      edge formation and can be interrupted at any stage. When the cup regresses,
      coronin dissociates from the site of accumulation. TRITC-labeled yeast cells have
      been used to assay phagocytosis quantitatively in wild-type and coronin-null
      cells. In the mutant, the rate of uptake is reduced to about one third, which
      shows that coronin contributes to the efficiency of phagocytosis to about the
      same extent as it improves the speed of cell locomotion.

PMID- 8521516
TI  - The tomato gene Pti1 encodes a serine/threonine kinase that is phosphorylated by
      Pto and is involved in the hypersensitive response.
AB  - The Pto gene encodes a serine/threonine kinase that confers resistance to
      bacterial speck disease in tomato. Using the yeast two-hybrid system, we
      identified a second serine/threonine kinase, Pto-interacting 1 (Pti1), that
      physically interacts with Pto. Cross-phosphorylation assays revealed that Pto
      specifically phosphorylates Pti1 and that Pti1 does not phosphorylate Pto. Fen,
      another serine/threonine kinase from tomato that is closely related to Pto, was
      unable to phosphorylate Pti1 and was not phosphorylated by Pti1. Expression of a
      Pti1 transgene in tobacco plants enhanced the hypersensitive response to a P.
      syringae pv. tabaci strain carrying the avirulence gene avrPto. These findings
      indicate that Pti1 is involved in a Pto-mediated signaling pathway, probably by
      acting as a component downstream of Pto in a phosphorylation cascade.

PMID- 8521517
TI  - Viral RNA as a potential target for two independent mechanisms of replicase
      mediated resistance against cucumber mosaic virus.
AB  - Transgenic tobacco showing replicase-mediated resistance against cucumber mosaic
      virus (CMV) can be infected by the strain K-CMV. By use of chimeric constructs
      between full-length cDNA clones of RNA2 of strains Fny-CMV and K-CMV, the
      existence of two independent mechanisms of replicase-mediated resistance against
      viral replication and movement of Fny-CMV was demonstrated in these plants. The
      data indicate that viral RNA may serve as the target for both mechanisms of
      resistance. A positive correlation was observed between the amount of K-CMV RNA2
      sequence present in the chimeric constructs and the ability to overcome the
      inhibition of replication, whereas a sequence domain was delimited in K-CMV RNA2
      responsible for the ability of this strain to break resistance against virus
      movement.

PMID- 8521518
TI  - Why is DsbA such an oxidizing disulfide catalyst?
AB  - DsbA, a member of the thioredoxin family of disulfide oxidoreductases, acts in
      catalyzing disulfide bond formation by donating its disulfide to newly
      translocated proteins. We have found that the two central residues within the
      active site Cys-30-Pro-31-His-32-Cys-33 motif are critical in determining the
      exceptional oxidizing power of DsbA. Mutations that change these two residues can
      alter the equilibrium oxidation potential of DsbA by more than 1000-fold. A
      quantitative explanation for the very high redox potential of DsbA was found by
      measuring the pKa of a single residue, Cys-30. The pKa of Cys-30 varied
      dramatically from mutant to mutant and could accurately predict the oxidizing
      power of each DsbA mutant protein.

PMID- 8521519
TI  - Suprabasal integrin expression in the epidermis of transgenic mice results in
      developmental defects and a phenotype resembling psoriasis.
AB  - Integrin expression is normally confined to the basal layer of the epidermis, but
      when epidermal homeostasis is perturbed, the receptors are also expressed by
      suprabasal, differentiating keratinocytes. We have used the involucrin promoter
      to express functional human integrin subunits alpha 2, alpha 5, and beta 1 in the
      suprabasal epidermal layers of transgenic mice. In mice expressing alpha 5 or
      beta 1 alone or alpha 2 beta 1 or alpha 5 beta 1 heterodimers, there were hair
      and whisker abnormalities and a failure of eyelid fusion. In addition, mice
      expressing beta 1 alone or in combination with alpha 2 or alpha 5 exhibited
      epidermal hyper-proliferation, perturbed keratinocyte differentiation, and skin
      inflammation, all of which are features of a common human skin disease,
      psoriasis.

PMID- 8521520
TI  - Mechanism by which Liddle's syndrome mutations increase activity of a human
      epithelial Na+ channel.
AB  - Liddle's syndrome is an inherited form of hypertension caused by mutations that
      truncate the C-terminus of human epithelial Na+ channel (hENaC) subunits.
      Expression of truncated beta and gamma hENaC subunits increased Na+ current.
      However, truncation did not alter single-channel conductance or open state
      probability, suggesting there were more channels in the plasma membrane.
      Moreover, truncation of the C-terminus of the beta subunit increased apical cell
      surface expression of hENaC in a renal epithelium. We identified a conserved
      motif in the C-terminus of all three subunits that, when mutated, reproduced the
      effect of Liddle's truncations. Further, both truncation of the C-terminus and
      mutation of the conserved C-terminal motif increased surface expression of
      chimeric proteins containing the C-terminus of beta hENaC. Thus, by deleting a
      conserved motif, Liddle's mutations increase the number of Na+ channels in the
      apical membrane, which increases renal Na+ absorption and creates a
      predisposition to hypertension.

PMID- 8521521
TI  - Aplysia CREB2 represses long-term facilitation: relief of repression converts
      transient facilitation into long-term functional and structural change.
AB  - The switch from short- to long-term facilitation induced by behavioral
      sensitization in Aplysia involves CREB-like proteins, as well as the immediate
      early gene ApC/EBP. Using the bZIP domain of ApC/EBP in a two-hybrid system, we
      have cloned ApCREB2, a transcription factor constitutively expressed in sensory
      neurons that resembles human CREB2 and mouse ATF4. ApCREB2 represses ApCREB1
      mediated transcription in F9 cells. Injection of anti-ApCREB2 antibodies into
      Aplysia sensory neurons causes a single pulse of serotonin (5-HT), which induces
      only short-term facilitation lasting minutes, to evoke facilitation lasting more
      than 1 day. This facilitation has the properties of long-term facilitation: it
      requires transcription and translation, induces the growth of new synaptic
      connections, and occludes further facilitation by five pulses of 5-HT.

PMID- 8521522
TI  - Alternative reading frames of the INK4a tumor suppressor gene encode two
      unrelated proteins capable of inducing cell cycle arrest.
AB  - The INK4a (MTS1, CDKN2) gene encodes an inhibitor (p16INK4a) of the cyclin D
      dependent kinases CDK4 and CDK6 that blocks them from phosphorylating the
      retinoblastoma protein (pRB) and prevents exit from the G1 phase of the cell
      cycle. Deletions and mutations involving INK4a occur frequently in cancers,
      implying that p16INK4a, like pRB, suppresses tumor formation. An unrelated
      protein (p19ARF) arises in major part from an alternative reading frame of the
      mouse INK4a gene, and its ectopic expression in the nucleus of rodent fibroblasts
      induces G1 and G2 phase arrest. Economical reutilization of coding sequences in
      this manner is practically without precedent in mammalian genomes, and the
      unitary inheritance of p16INK4a and p19ARF may underlie their dual requirement in
      cell cycle control.

PMID- 8521523
TI  - Biodegradable microspheres in drug delivery.
AB  - General aspects of biodegradable microspheres prepared from natural and
      synthesized polymers used in drug delivery systems are reviewed first from
      various viewpoints: characteristics of biodegradable polymers (physicochemical
      properties, bioerosion mechanism, biocompatibility), preparation method for the
      microspheres, drug release from parenteral products and briefly nonparenteral
      products. The relationship between release pattern and pharmacological activity
      of therapeutic peptides and proteins and rational controlled release design are
      also discussed. In the latter half, successful sustained release depot
      formulations of peptides, leuprorelin acetate, and thyrotropin-releasing hormone
      (TRH), utilizing poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA)
      microspheres are reviewed with respect to preparation, drug release,
      biocompatibility, pharmacological effects, and results of clinical studies.
      Thereafter, studies on antitumor therapy by chemoembolization using PLGA
      microspheres containing an angiogenesis inhibitor (TNP-470) are described as an
      example of targeted drug delivery with biodegradable microspheres.

PMID- 8521524
TI  - Immunocytochemical study of microvilli in a gastric carcinoma-derived cell line.
AB  - To study the structural components of microvilli of the KATO-III cell, we used
      anti-villin, -ezrin, and anti-MVM (microvillous membrane prepared against mouse
      intestinal microvilli) antibodies. Villin and ezrin cross-link actin bundles of
      microvilli such as those in the small intestine and renal proximal cells.
      Electromicroscopically, the cytoskeletal core of microvilli of the KATO-III cell
      was constituted of actin-filament bundles. The anti-villin antibody but not anti
      ezrin antibody reacted with the KATO-III cell as demonstrated by FITC
      immunofluorescence and PAP-staining. Anti-villin, anti-MVM, but not anti-ezrin
      antibody, reacted with the KATO-III cell surface and with intracellular
      materials. Western blot analysis using anti-villin and anti-MVM antibodies
      revealed proteins of approximately 95 kDa (villin), and 15 kDa in the microsomal
      membrane fractions of KATO-III cells, respectively. Immunocytochemical and
      confocal laser microscopic studies showed that the cell-surface and the
      intracellular microcysts of KATO-III cells were preferentially decorated by anti
      villin and anti-MVM antibodies. These data suggested that some actin-binding
      proteins, such as villin, were localized at the cell surface and on some of the
      intracellular cytoplasmic structures of the KATO-III cell.

PMID- 8521525
TI  - Assembly of cardiac C-protein during myofibrillogenesis in myogenic cells in
      culture.
AB  - To examine the function of C-protein, a thick filament-associated protein of
      vertebrate striated muscles, during myofibrillogenesis, the cDNA encoding chicken
      cardiac C-protein and the truncated cDNA were subcloned into a expression vector
      and introduced into mouse C2 myogenic cells. The expression and assembly of the C
      protein was investigated by immunofluorescence methods. When the cDNA containing
      the entire open reading frame was introduced, in C2 myoblasts, the transiently
      expressed exogenous cardiac C-protein existed only diffusely in the cytoplasm,
      but it became localized in striated structures together with sarcomeric myosin
      heavy chains (MHC) in myotubes. To clarify the functional domains of C-protein,
      the cDNA constructs that lack the regions encoding the C-terminal immunoglobulin
      (Ig) C2 motif or the N-terminal Ig C2 motif were introduced into C2 cells to
      produce mutant proteins. The truncated chicken cardiac C-protein, which lacked
      the C-terminal Ig C2 motif, apparently lost the ability to bind to myosin
      filaments; the protein was not assembled into myofibrils but diffused in the
      cytoplasm even in the myotubes. The protein without N-terminal Ig C2 motif,
      however, was assembled into sarcomeric structures just as complete protein
      molecules. From these results, we conclude that 1) the assembly of sarcomeric MHC
      into myofibrils in myotubes is accompanied with that of cardiac C-protein, and 2)
      the C-terminal Ig C2 motif is necessary for assembly of cardiac C-protein in
      sarcomeric structures in the cytoplasm.

PMID- 8521526
TI  - cDNA cloning and sequence analysis of a novel calcium binding protein with
      oligoproline motif.
AB  - Using antibodies against pokeweed agglutinin-binding proteins from F9 embryonal
      carcinoma cells, we isolated a cDNA clone PW29 reacting with the antibody. mRNA
      hybridizing with the cDNA was 4.7 kb, and was strongly expressed in the testis,
      brain, kidney and heart as well as in F9 cells. The size of mRNA in the testis
      was heterogeneous. Sequencing the cDNA clone revealed a putative polypeptide of
      70 kDa, which is rich in hydrophilic amino acids and has a characteristic
      sequence of (Glu(Lys))5. The protein also has an oligoproline motif, which
      conforms to the rule of binding capability to Src homology region III. The cDNA
      was translated as a fusion protein with glutathione-S-transferase, and was
      verified to have calcium binding activity, upon a calcium blot experiment.

PMID- 8521527
TI  - Fatty acid composition of ganglioside GM3 of renal glomerular epithelial SGE1
      cells during spontaneous dome formation in vitro.
AB  - Ganglioside GM3, one of acidic components of membrane glycosphingolipids (GSL),
      has been known to change its content quantitatively during growth and
      differentiation of various cells in vitro. Detailed analysis of lipid portion of
      GM3 of rat renal glomerular SGE1 cells revealed that fatty acids with long carbon
      chains, especially that of C24:0 and C24:1 increased, while that of short C18:0
      and C20:0 decreased after spontaneous dome formation. Since not only fatty acid
      composition of neutral GSL, sulfatide and phospholipid but also composition of
      long-chain bases (LCB) did not change, it was suggested that only C24 fatty acid
      of GM3 specifically increased in relation to dome formation. The spontaneous dome
      formation has been reported to be related with induction of cellular
      differentiation in many transporting epithelial cells. We thus assume that the
      change of fatty acid composition of GM3 is involved in cellular differentiation
      of SGE1 cells.

PMID- 8521528
TI  - Evidence of participation of cytoskeleton of heart muscle cells during the
      invasion of Trypanosoma cruzi.
AB  - The participation of heart muscle cells (HMC) cytoskeleton during its interaction
      with Trypanosoma cruzi was investigated. Pre-treatment of heart muscle cells with
      cytochalasin B (CB) or D (CD) prior to 1 and 3 h of interaction with T. cruzi
      inhibited the uptake of parasites by about 65% and 75%. T. cruzi was not able to
      invade fixed HMC, and fixed parasites were not internalized in either normal and
      CD-treated HMC. Transmission electron microscopy showed cell membrane projections
      of HMC enclosing the parasite during the invasion process after short periods of
      interaction (5 to 30 min). During the parasite internalization process,
      sarcolemma extensions were observed inside the cytoplasmic vacuole, suggesting
      that the endocytic event may involve internalization of a "self membrane". Images
      of cytoskeleton elements mobilization during T. cruzi penetration of HMC were
      obtained following treatment of cells with Triton X-100. Our results suggest an
      active involvement of HMC cytoskeleton elements during the interiorization of
      metacyclic forms of T. cruzi.

PMID- 8521529
TI  - Temperature-sensitive mutation of DNA polymerase alpha induces growth-suppressive
      phenotypes involving retinoblastoma protein and cyclin D1.
AB  - Temperature-sensitive (ts) cell cycle mutant mouse cell, tsFT20, is deficient in
      DNA polymerase alpha activity to initiate DNA replication at replicon origins.
      Here, we analyzed phenotypes concerning growth control genes in the arrested
      tsFT20 cells. Analysis of cyclins showed that expression levels of cyclin D1,
      which is essential for G1/S transition, remarkably decreased in the mutant cells
      after temperature up-shift. Further we examined phosphorylation states of
      retinoblastoma protein (pRB) in the cells. Though the tsFT20 cells arrested in
      G1/S-S phase at nonpermissive temperature (Eki et al., (1990) J. Biol. Chem. 265
      26-33), a large proportion of pRB was found as an underphosphorylated growth
      suppressive form in the arrested cells. In revertant cell lines of tsFT20, pRB
      was not underphosphorylated even at nonpermissive temperature. The pRB
      underphosphorylation occurred later than the decrease of mRNA levels of cyclin
      D1, thus the underphosphorylation may be caused by the decrease in amount of
      cyclin D1 protein. These results indicated that the mutational inactivation of
      DNA polymerase alpha evokes phenotypes in which the inhibitory machinery of G1/S
      transition has been turned on.

PMID- 8521530
TI  - Sperm morphology and IMP distribution in membranes of spermatozoa of cyprinid
      fishes II.
AB  - The morphology and intramembranous particle (IMP) distribution of spermatozoa
      were investigated in four species of cyprinid fishes, Gnathopogon elongatus
      elongatus, Pseudogobio esocinus, Acheilognathus lanceolatus and Puntius
      tetrazona. In particular, observation of IMP distribution was conducted as an
      aspect of comparative spermatology in cyprinid fishes and was continued from a
      previous paper (Ohta et al., 1994 (8)). Although the fundamental structures of
      the spermatozoa were similar among the four species, the distribution of IMPs
      varied. Hexagonal (or parallelogrammic) arrays of IMPs on the sperm head
      membranes were present in G. elongatus elongatus, A. lanceolatus and P.
      tetrazona, but not in P. esocinus. The hexagonal arrays have now been confirmed
      to be present in twelve of the thirteen species of cyprinid fishes examined so
      far.

PMID- 8521531
TI  - Physicochemical behavior of the ganglioside GM3 in dilute aqueous solution.
AB  - The aggregative properties of the ganglioside GM3 have been studied with small
      angle X-ray scattering and dynamic light scattering in dilute aqueous solutions.
      Dynamic light scattering experiments show that GM3 solutions are very
      polydisperse containing a large amount of small aggregates (hydrodynamic radius
      of 7-9 nm) in addition to a quite broad distribution of aggregates with an
      average hydrodynamic radius of 50-60 nm and a small fraction of very large
      aggregates (> 200 nm). This together with small-angle X-ray scattering scattering
      experiments and model calculations suggests the coexistence of a lamellar phase
      (vesicles or extended lamellae) with small aggregates (modelled as lamellar
      platelets). The latter can also be viewed as lamellar fragments coming from GM3
      vesicles which constantly break and reform.

PMID- 8521532
TI  - The action of hypochlorous acid on phosphatidylcholine liposomes in dependence on
      the content of double bonds. Stoichiometry and NMR analysis.
AB  - Kinetics of the consumption of hypochlorous acid in its reaction with double
      bonds of unsaturated phospholipids and fatty acids were measured using luminol
      chemiluminescence. Stoichiometry ratios between the consumption of HOCl/OCl- and
      the loss of double bonds vary from 2:1 to 1:1. Highest values were found in DMPC
      liposomes containing 5 mol% oleic acid or OPPC. With increasing content of double
      bonds or higher numbers of double bonds in a fatty acid acyl chain due to
      incorporated unsaturated fatty acids or phospholipids in DMPC liposomes the
      stoichiometry ratio falls continuously to 1:1. A ratio of about 1:1 was observed
      in multilamellar and unilamellar liposomes composed of egg yolk
      phosphatidylcholine. Products of the reaction of oleic acid with hypochlorous
      acid were analyses by 1H-NMR spectroscopy. Chlorohydrins were formed in both DMPC
      liposomes containing 5 or 40 mol% oleic acid.

PMID- 8521533
TI  - 2-modified 1,3-diacylglycerols as new surfactants for the formation of reverse
      micelles.
AB  - New 2-modified 1,3-diacylglycerols such as 1,3-dilauroylglycerol 2
      disodiumphosphate and analogues were characterized with respect to their tendency
      to form reverse micelles in isooctane and isooctane/1-hexanol. The water content
      of the reverse micelles was determined by Karl-Fischer titration. The critical
      micelle concentration of the compounds was estimated by fluorescence measurements
      using rhodamine B as indicator. The concentration regions where reverse micelles
      are observed were characterized by pseudoternary phase diagrams. The ability of
      the surfactants to extract proteins into the organic phase was examined for
      cytochrome c. The properties of the new compounds were compared with the
      behaviour of the corresponding regioisomeric 3-modified 1,2-diacylglycerols as
      well as lecithin and the surfactant AOT, which is preferably used for the
      formation of reverse micelles. The results suggest that the position of the head
      group in the modified diacylglycerols is of low importance for the phase
      behaviour whereas the ability to form reverse micelles decisively depends on the
      kind of the head group.

PMID- 8521534
TI  - Structure of digalactosyldiacylglycerol from oats.
AB  - Digalactosyldiacylglycerol (DGalDAG) is one of the major lipids in the cells of
      higher plants. DGalDAG forms a lamellar liquid crystalline phase together with
      water. Lipid aggregates can thus be prepared which are of potential interest for
      use within the cosmetic and pharmaceutical industries. Oats may be an important
      source for preparation of DGalDAG, but the structure has not been determined for
      the DGalDAG lipid occurring in this plant. In the present study the structure of
      a high-purity DGalDAG preparation, isolated from commercial oat flakes, was
      determined by high resolution 1H- and 13C-NMR spectroscopy. The lipid was found
      to have the structure 1,2-diacyl-3-O-[alpha-galactopyranosyl-(1-->6)-O-beta
      galactopyranosyl]- glycerol. By using 1H- and 13C-NMR spectroscopy techniques it
      is thus possible to determine, among other things, the identity of the glycosyl
      moieties in the polar head group, to establish the linkage positions between
      these moieties, and to establish the anomeric configurations of the moieties,
      without making any chemical modifications of the lipid.

PMID- 8521535
TI  - [Progression in 25 years of artificial nutrition in surgery].
AB  - The Authors illustrate the fundamental steps of development of artificial
      nutrition (AN) during the last 25 years. In this period AN has been extensively
      experimented with and applied clinically, as total parenteral nutrition as well
      as enteral nutrition. The indications for artificial nutrition have been
      characterised and numerous experimental and clinical studies have been carried
      out to document the effects of nutritional support in surgical patients. The
      results of such studies have entranced our knowledge of nutritional
      pathophysiology and have brought about better methods for AN in surgery. As a
      result, surgical complications in malnourished patients have been significantly
      reduced by means of artificial nutritional support.

PMID- 8521536
TI  - [Immunologic aspects of artificial nutrition].
AB  - Artificial nutrition (AN) has become an essential part of traumatised and
      surgical patient care. The main indications for AN are severe undernutrition and
      hypermetabolism, which are important causes of immunosuppression. Total
      parenteral nutrition has proved to be as beneficial in the perioperative period
      only in malnourished subjects. In contrast, overfeeding may cause detrimental
      sequelae with an increase in postoperative complications. Experimental and
      clinical trials have clearly shown that the administration of nutrients via the
      enteral route versus the parenteral one has several advantages, including
      improved local and systemic immune response and gut barrier function with the
      subsequent reduction of septic morbidity. Preliminary data in traumatised and
      surgical patients have shown further immunological and clinical advantages when
      the composition of the enteral solutions has been enriched with specific
      nutrients capable of enhancing the host defence mechanisms. The most important
      are arginine, n-3 fatty acids, RNA, and glutamine.

PMID- 8521537
TI  - [The choice of substrates in total parenteral nutrition].
AB  - This review contains a full outline on the choice of substrates in total
      parenteral nutrition (NPT). The basic properties of "conventional" substrates
      (glucose, long chain triglyceride-containing fat, common amino acid mixtures) are
      used to outline the general principles for NPT support in normal conditions and
      in stress (surgical and nonsurgical trauma, sepsis). Without taking into account
      factors which are not strictly metabolic (vascular access, local availability of
      products, costs), particular attention is then paid to "non-conventional"
      substrates and substrate mixtures, including some under study, with specific
      reference to properties and features which may motivate their choice.

PMID- 8521538
TI  - [The use of lipids in total parenteral nutrition].
AB  - Lipid infusion, once used solely as a means of preventing fatty acid deficiency,
      is now commonly used as a major caloric source in total parenteral nutrition. The
      Authors propose a review of problems related to the use of intravenous fat
      emulsions.

PMID- 8521539
TI  - [Immediate post-operative enteral nutrition].
AB  - Patients with cancer of the upper digestive tract may present with malnutrition,
      which may cause immunodepression and an increased rate of postoperative
      complications. In this study we describe the rationale and the feasibility of
      immediate postoperative enteral nutrition (NEPI) and evaluate its effectiveness
      for the nutritional support of patients undergoing surgery of the upper digestive
      tract. We studied 46 patients undergoing the following procedures: total
      gastrectomy (n = 22); oesophageal resection (n = 12);
      duodenocephalopancreasectomy (n = 12). NEPI was started on postoperative day 0
      with a polymeric diet (calories: 53% as CHO, 22% as proteins, 25% as lipids)
      aiming at a calorie intake of 25 Kcal/Kg/day by postoperative day 4. It was
      possible to administer 24 Kcal/kg/day with the enteral diet from the 4th to the
      10th postoperative day. Oral intake was resumed on average on postoperative day
      13, and the mean hospital stay was 27 +/- 17 days. Tolerance of NEPI was good in
      most patients: only 5 patients (11%) interrupted the enteral nutrition. The mean
      postoperative weight loss was 3.7%. The rate of septic complications was 27%;
      mortality was nil. The surgical procedures caused a transient and reversible
      acute-phase decrease of nutritional and immunological parameters in the early
      postoperative period. However the NEPI preserved the nutritional status
      postoperatively as shown by the lack of significant changes in the nutritional
      indices at 10-14 days after surgery, as compared with baseline. In summary, we
      documented that NEPI can be started from postoperative day 0 with good intestinal
      tolerance, allowing adequate nutritional support, after extensive surgical
      procedures on the upper digestive tract.

PMID- 8521540
TI  - [Artificial nutrition in the management of lesions caused by caustic ingestion].
AB  - Ingestion of a large amount of corrosive agent results in a life-threatening
      condition which requires a much more aggressive diagnostic and therapeutic
      approach than was formerly recommended. Based on experience with a wide spectrum
      of upper g-i injuries in 56 patients treated through a 5-year-period, the Authors
      suggest an early staging of the lesions by immediate endoscopy, followed by
      adequate resective surgery for high-degree esophago-gastric lesions. Indications,
      techniques of artificial nutrition and the nutritional requirements of this
      condition are presented and fully discussed. The prompt institution of total
      parenteral nutrition is an essential part of the emergency management of these
      lesions. Fourteen patients underwent surgical treatment for the lesions; in all
      cases a Witzel's feeding jejunostomy was performed and postoperative enteral
      nutrition was started. Eight patients underwent a reconstructive operation of
      colon interposition and received home-based total enteral nutrition for a period
      of 8-25 weeks. No major complications relate to nutritional support occurred and
      nutritional indexes were normal at the end of the treatment.

PMID- 8521541
TI  - [Artificial nutrition in the injured patient].
AB  - Current knowledge of physiopathology allows better understanding of the metabolic
      and immunological alterations that occur after trauma, thus allowing more
      adequate treatment. Nutritional support is recognized as an important therapeutic
      intervention to promote wound healing, reduce the risk of infection and improve
      survival. The patient with severe trauma needs nutritional support from the
      beginning of treatment. The early administration of enteral nutrition is an
      important factor in the reduction of gut bacterial translocation and thus of
      septic complications. In the early phase, the parenteral route is capable of
      providing a sufficient calorific and protein support, whilst awaiting the
      recovery of the enteral route.

PMID- 8521542
TI  - [Artificial (parenteral and enteral) nutrition in postoperative rehabilitation].
AB  - Post-surgical rehabilitation requires a full knowledge of the physiopathological
      basis and a great capacity to evaluate with specific tools, essential function
      and variations of digestive system. These problems have been underlined by the
      Authors specifically for gastric surgery in general, for movement factors of
      intestinal surgery and related nutritional implications for Crohn's disease,
      chronic intestinal insufficiency, enteric fistulas, severe exocrine pancreatic
      insufficiency, related to resective pancreatic surgery and for external
      pancreatic fistulas. The last words have been devoted to peri-operative
      parenteral nutrition.

PMID- 8521543
TI  - [Ambulatory hemorrhoidectomy: results of 500 surgical operations].
AB  - To evaluate the results of outcome hemorrhoidectomy, 500 Ferguson-Khubchandani's
      operations performed between January 1989 and December 1993, were reviewed. 272
      of the patients (54.4%) were males (average age 37 years). In 76.6% of patients
      haemorrhoids were III degree. After outcome pre-operative study, the patients
      were operated using local anaesthesia and discharged two hours after the
      operation. Telephone contact was established with patients until the 6th day
      after surgery and they were reviewed 7 and 14 days after operation. 320 patients
      were followed up for 12 months. The results were evaluated on the basis of the
      following criteria: grading of post-operative pain; complications and late
      sequelae; grading of patients satisfaction with the surgical operation. 291
      patients (39.2%) reported light post-operative pain; in 61 (12.2%) the pain was
      high and needed multiple analgesic (ketorolac) infusions. Post-operative
      complications were respectively: haemorrhage (7 cases); perianal abscess (2
      cases); transitory gas incontinence (3 cases). Late sequela were: II degree
      stenosis (2 cases) and return of haemorrhoids (3 cases). In 89.9% of patients
      results were well satisfactory. 2% of patients were not satisfied with the
      operation. This study and the literature confirm the technical improvement in
      hemorrhoidectomy: with the introduction of new antalgic drugs, this procedure is
      now well established in an ambulatory setting with good results and low cost.

PMID- 8521544
TI  - [Assessment of the nutritional status of the surgical patient].
AB  - Since malnutrition has been demonstrated as increasing surgical risk in terms of
      post-operative morbidity and mortality, simple and feasible methods of evaluating
      nutritional status have been investigated. Epidemiological studies, carried out
      mainly in populations with gastrointestinal diseases, allowed selection of some
      simple indices (weight loss, albumin, transferrin, circulating lymphocytes and
      delayed hypersensitivity response to cutaneous antigens) which are useful in
      assessing the patient's altered nutritional status. The same results can be
      obtained by clinical examination only, if this is conducted by a trained
      physician. The conclusions of investigations of nutritional assessment parameters
      and of multiparametric indices are controversial. Non-nutritional factors are
      often involved in the occurrence of post-operative complications, interfering
      with the predictive value of the nutritional status indicators.

PMID- 8521545
TI  - [Complications in a patient with a jejuno-peritoneal shunt by the Le Veen
      technique].
AB  - The case of a patient, who, 3 months after application of a Le Veen shunt for a
      refractory ascites, underwent the pleural effusion of ascitic fluid is reported.
      The adoption of a scintigraphic diagnostic technique allowed the demonstration of
      a direct ascitic fluid passage from the peritoneal to the pleural cavity and the
      subsequent successful pleurodesis, performed using an application of local
      tetracycline.

PMID- 8521546
TI  - [Peritoneal mesothelioma as a rare case of acute abdomen. Review of the
      literature].
AB  - Peritoneal mesothelioma is a rare neoplasm with generic and non-specific
      symptoms. In some cases it is associated with various and particular clinical
      syndromes. These findings make it so insidious that the diagnosis is rarely make
      the preoperative course. Usually, there has been previous exposure to asbestos,
      during even if other causes are reported. Rarely, a peritoneal mesothelioma
      appears with signs and symptoms suggestive of acute abdomen, such as the present
      case. On admission the patient presented clinical features apparently requiring
      emergency surgery. In fact, at laparotomy, the tumour, arising from the
      mesenterium, had perforated the peritoneal cavity and communicated with the
      digiunal lumen, causing a septic hemoperitoneum. A radical resection was
      performed and the continuity of the intestinal tract was restored through an end
      to-end entero-anastomosis. The patient, with a history of exposure to asbestos,
      was alive four years later. But over the last twelve months diffuse metastasis
      has occurred in the lung and liver, and there was no response to systemic
      chemotherapy. This case may be considered singular of the clinical syndrome, the
      long-term survival and the circumscribed aspect of the tumour. Through a review
      of the literature, the features of the present diagnostic procedure are
      underlined and the importance of multidisciplinary treatment as the best approach
      to peritoneal mesothelioma is emphasized.

PMID- 8521547
TI  - [Postoperative ischemic ileocolitis in the elderly. Suggested therapy with
      intraluminal administration of oxygen and glutamine].
AB  - Ischaemic ileocolitis in postoperative course of major abdominal surgery is a
      great challenge for the surgeon: the mortality rate is very high, and therapeutic
      choices are poor. In the elderly patients ischaemic bleeding ileocolitis is often
      determined by low flow: sepsis and cytologic damage are primed by activation of
      endotoxins and chemical mediators, and bacterial translocation could develop
      across intestinal wall. In our case the patient (male, caucasian, 68 years old)
      underwent bilio-hepatic resection for hilar cholangiocarcinoma. In the
      postoperative period continuous enteric haemorrhage was determined by an
      ischaemic ileocolitis demonstrated by colonoscopy. Abdominal angiography did not
      show stenosis or occlusion of mesenteric vessels. We administered dopamine and
      dobutamine as vasodilator drugs for splanchnic circulation without any positive
      response. Surgical removal of the colon was unsuccessful to stop bleeding.
      ileostomy and sigmostomy were performed. Histologic samples of the specimen
      showed ischaemic ileocolitis. After a few days the patient bled again. As last
      therapeutic choice, we bubbled oxygen in a solution of L-glutamin 500 mml (3
      liters/min for 5 min). We administered 500 mml of this solution three times a day
      by enteral sond, and 100 mml twice a day by sigmoidostomy and endoluminal
      oxygenation was performed twice a day (1l/min for 1-2 minutes) under continuous
      control. Bleeding was reducing during the next five days, until stopping. If
      glutamine and O2 can be considered the fuel of enterocytes, we hypothesized
      endoluminal oxygenation and glutamine enteral supply of the small intestine could
      feeding enterocytes, until a complete restoration of enteral mucosa and stopping
      of the haemorrhage.

PMID- 8521549
TI  - AHA's new research initiative.

PMID- 8521548
TI  - [Surgical repair of congenital penile curvature].
AB  - Congenital penile curvature is not such a rare pathology and it is responsible
      for important aesthetic and functional problems. This malformation, can render
      intercourse difficult and painful, but it can be cured with a simple surgical
      procedure that almost always guarantees excellent results. In this work we report
      on the treatment of 48 patients (aged 16-34) with congenital penile curvature
      with a follow-up of 6 months to 10 years. The aetiology is also briefly analysed.
      A discussion follows on the diagnostic criteria for better interpretation of the
      main characteristics of this problem in relation to its functional appearance. A
      comparison of different surgical techniques is also shown, focusing over the
      procedure we perform: plissettage of the tunica albuginea. This technique is
      performed through a penile skin incision opposite to the maximal curvature of the
      organ, exposure of the tunica albuginea and the positioning of one or more series
      of stitches. The overall results show that 44 out of 48 patients were fully
      satisfied both from the aesthetic and functional points of view, while 4 were
      partly satisfied from the aesthetic point of view alone.

PMID- 8521550
TI  - NHLI BARI clinical alert on diabetics treated with angioplasty.

PMID- 8521551
TI  - Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart
      failure. Endothelin antagonism in heart failure.

PMID- 8521552
TI  - Long QT syndrome patients with gene mutations.

PMID- 8521553
TI  - Significance of Chlamydia pneumoniae (TWAR) in atherosclerotic lesions.

PMID- 8521554
TI  - Diagnostic significance of impaired LV systolic relaxation in heart failure.

PMID- 8521555
TI  - Long QT syndrome patients with mutations of the SCN5A and HERG genes have
      differential responses to Na+ channel blockade and to increases in heart rate.
      Implications for gene-specific therapy.
AB  - BACKGROUND: The genes for the long QT syndrome (LQTS) linked to chromosomes 3
      (LQT3) and 7 (LQT2) were identified as SCN5A, the cardiac Na+ channel gene, and
      as HERG, a K+ channel gene. These findings opened the possibility of attempting
      gene-specific control of ventricular repolarization. We tested the hypothesis
      that the QT interval would shorten more in LQT3 than in LQT2 patients in response
      to mexiletine and also in response to increases in heart rate. METHODS AND
      RESULTS: Fifteen LQTS patients were studied. Six LQT3 and 7 LQT2 patients were
      treated with mexiletine, and its effects on QT and QTc were measured. Mexiletine
      significantly shortened the QT interval among LQT3 patients (QTc from 535 +/- 32
      to 445 +/- 31 ms, P < .005) but not among LQT2 patients (QTc from 530 +/- 79 to
      503 +/- 60 ms, P = NS). LQT3 patients (n = 7) shortened their QT interval in
      response to increases in heart rate much more than LQT2 patients (n = 4) and also
      more than 18 healthy control subjects (9.45 +/- 3.3 versus 3.95 +/- 1.97 and 2.83
      +/- 1.33, P < .05; data expressed as percent reduction in QT per 100-ms
      shortening in RR). Among these patients, there is also a trend for LQT2 patients
      to have syncope or cardiac arrest under emotional or physical stress and for LQT3
      patients to have cardiac events either at rest or during sleep. CONCLUSIONS: This
      is the first study to demonstrate differential responses of LQTS patients to
      interventions targeted to their specific genetic defect. These findings also
      suggest that LQT3 patients may be more likely to benefit from Na+ channel
      blockers and from cardiac pacing because they would be at higher risk of
      arrhythmia at slow heart rates. Conversely, LQT2 patients may be at higher risk
      to develop syncope under stressful conditions because of the combined
      arrhythmogenic effect of catecholamines with the insufficient adaptation of their
      QT interval when heart rate increases.

PMID- 8521556
TI  - Localization of a gene responsible for familial dilated cardiomyopathy to
      chromosome 1q32.
AB  - BACKGROUND: Dilated cardiomyopathy, characterized by ventricular dilatation and
      decreased systolic contraction, is twofold to threefold more common as a cause of
      heart failure than hypertrophic cardiomyopathy and costs several billion dollars
      annually. The idiopathic form occurring early in life, with a 75% mortality in 5
      years, is a common reason for transplantation. It is estimated that at least 20%
      of cases are familial. METHODS AND RESULTS: A family of 46 members spanning four
      generations underwent history and physical examinations, echocardiographic
      analysis, and blood sampling for genotyping. Diagnostic criteria, detected by
      echocardiography, consisted of ventricular dimension of > or = 2.7 cm/m2 with an
      ejection fraction < or = 50% in the absence of other potential causes. DNA from
      all members was analyzed by polymerase chain reaction for amplification of short
      tandem-repeat polymorphic markers located every 10 cM throughout the human
      genome. Assuming a penetrance of 90%, linkage analysis was performed to map the
      responsible chromosomal locus. Linkage analysis, after 412 markers were analyzed,
      indicated the locus to be on chromosome 1q32, with a peak multipoint logarithm of
      the odds score at D1S414 of 6.37. CONCLUSIONS: The locus identified in this study
      for familial dilated cardiomyopathy, 1q32, is rich in candidate genes, such as
      MEF-2, renin, and helix loop helix DNA binding protein MYF-4. Identification of
      the genetic defect could provide insight into the molecular basis for the cardiac
      dilatory response in both familial and acquired disorders.

PMID- 8521557
TI  - The insertion allele of the ACE gene I/D polymorphism. A candidate gene for
      insulin resistance?
AB  - BACKGROUND: The insertion/deletion (ID) polymorphism of the angiotensin
      converting enzyme (ACE) gene has been associated with increased coronary heart
      disease (CHD), although the mechanism of this association is not apparent. We
      tested the hypothesis that the deletion allele of the ACE gene is associated with
      insulin resistance. METHODS AND RESULTS: We related ACE genotype to components of
      the insulin-resistance syndrome in 103 non-insulin-dependent diabetic (NIDDM) and
      533 nondiabetic white subjects. NIDDM subjects with the DD genotype had
      significantly lower levels of specific insulin (DD 38.6, ID 57.1, and II 87.4
      pmol.L-1 by ANOVA, P = .011). Non-insulin-treated subjects with the DD genotype
      had increased insulin sensitivity by HOMA % (DD 56.4%, II 29.4%, P = .027) and
      lower levels of des 31,32 proinsulin (DD 3.3, II 7.6 pmol.L-1, P = .012) compared
      with II subjects. There were no differences in prevalence of CHD or levels of
      blood pressure, serum lipids, or plasminogen activator inhibitor-1 (PAI-1)
      activity between the three ACE genotypes. In nondiabetic subjects there were no
      differences in insulin sensitivity, levels of insulin-like molecules, blood
      pressure, PAI-1, serum lipids, or CHD prevalence between the three ACE genotypes.
      CONCLUSIONS: We conclude that increased cardiovascular risk of the DD genotype is
      not mediated through insulin resistance or abnormalities in fibrinolysis.
      Conversely, we report an increased sensitivity in NIDDM subjects with the ACE DD
      genotype.

PMID- 8521558
TI  - Therapeutic trial of sympathomimetics in three cases of complete heart block in
      the fetus.
AB  - BACKGROUND: A total of 36 fetuses with isolated congenital complete heart block
      and structurally normal hearts have been seen in the department of fetal
      echocardiography since 1980. Although the prognosis is good in the majority of
      cases, those who develop intrauterine cardiac failure have a high mortality. The
      aim of this study was to investigate the contribution to management of
      sympathomimetic therapy by comparing two possible agents administered to the
      mothers. METHODS AND RESULTS: The effect of two sympathomimetic agents,
      isoprenaline and salbutamol, was compared in three patients with isolated
      complete heart block. Fetal heart rate and indexes of cardiac function were
      monitored during therapy. Maternal cardiovascular status was also regularly
      assessed. Dosage of isoprenaline increased from 1 to 12 micrograms/min, and
      salbutamol increased from 4 to 64 micrograms/min during the trial. No significant
      change was detected with isoprenaline therapy, but all fetuses showed an increase
      in heart rate and improvement in ventricular function with salbutamol. Salbutamol
      was maintained until delivery in one case with evidence of cardiac failure, with
      resolution of fetal hydrops. All three delivered in good condition close to term.
      Two of three required pacing in the neonatal period. CONCLUSIONS: We conclude
      that salbutamol can be effective in the treatment of fetal complete heart block
      and should be considered in patients with this condition where there is evidence
      of deteriorating cardiac function.

PMID- 8521559
TI  - Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery.
AB  - BACKGROUND: Chlamydia pneumoniae has been demonstrated in atherosclerotic lesions
      of coronary arteries and aorta. A seroepidemiological study found C pneumoniae
      specific antibody more frequently in persons with significant carotid artery wall
      thickening than in matched control subjects. METHODS AND RESULTS: Fresh-frozen or
      formalin-fixed tissue obtained at carotid endarterectomy was examined by
      immunocytochemistry (ICC) and the polymerase chain reaction (PCR) for the
      presence of C pneumoniae. Five of five fresh-frozen and formalin-fixed carotid
      endarterectomy specimens were positive for C pneumoniae by ICC (three of five by
      PCR). A total of 56 archival formalin-fixed, paraffin-embedded carotid
      endarterectomy tissues from three hospitals were examined by ICC. Thirty-two were
      positive. Thirteen normal carotid artery tissue sections from six patients were
      negative for C pneumoniae. CONCLUSIONS: C pneumoniae organisms are frequently
      found in the advanced carotid atherosclerotic lesions of persons undergoing
      endarterectomy. Although these findings do not establish causality for C
      pneumoniae in carotid artery atherosclerosis, they should stimulate investigation
      of a possible causal or pathogenic role for the organism in the disease.

PMID- 8521560
TI  - Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial
      infarction in the emergency room.
AB  - BACKGROUND: Ruling out acute myocardial infarction (AMI) on the basis of rapid
      assays for cardiac markers will allow early triage of patients and cost-effective
      use of available coronary care facilities. METHODS AND RESULTS: We studied the
      value of myoglobin, creatine kinase (CK)-MBmass, and troponin T in ruling out an
      AMI in the emergency room in 309 consecutive patients presenting with chest pain.
      The gold standard for AMI was the combination of history, ECG, and a typical
      curve of the CK-MB activity (CK-MBact). Myoglobin was the earliest marker, and
      its negative predictive value (NPV) was significantly higher than for CK-MBmass
      and troponin T from 3 to 6 hours after the onset of symptoms (myoglobin versus CK
      MBmass, P < .03; myoglobin versus troponin T, P < .01). The NPV of myoglobin
      reached 89% 4 hours after the onset of symptoms. The NPV of CK-MBmass reached 95%
      7 hours after the onset of symptoms. Troponin T was not an early marker for
      ruling out AMI, and NPV changed over time, together with CK-MBact. The early NPV
      was higher in a subgroup of patients with a low probability of the presence of
      AMI for the three markers. Cardiac markers rise earlier in patients with large
      infarcts than in patients with small infarcts as indicated by the cumulative
      proportion of the marker above the upper reference limit at each time point
      (myoglobin, P = .04; CK-MBmass, P = .013; troponin T, P = .016). CONCLUSIONS: For
      ruling out AMI in the emergency room, myoglobin is a better marker than CK-MBmass
      or troponin T from 3 until 6 hours after the onset of symptoms, but the maximal
      NPV reaches only 89%. At 7 hours, the NPV of CK-MBmass is 95%. The test
      characteristics are influenced by the probability of the presence of AMI in the
      patients studied and by the size of their AMI. Infarct size of AMI patients
      should be reported in studies evaluating cardiac markers.

PMID- 8521561
TI  - Mechanisms of lumen enlargement after excimer laser coronary angioplasty. An
      intravascular ultrasound study.
AB  - BACKGROUND: The mechanisms of excimer laser coronary angioplasty (ELCA) have
      never been studied in human coronary arteries in vivo. METHODS AND RESULTS: ELCA
      was used to treat 202 lesions in 190 patients. Forty-nine lesions in 48 patients
      were studied by use of sequential (before and after ELCA and after adjunctive
      device therapy) intravascular ultrasound (IVUS). External elastic membrane (EEM),
      lumen, and plaque+media (P+M = EEM-lumen) cross-sectional areas (CSAs) and lesion
      arcs of calcium were measured before and after ELCA and after adjunct device use.
      Lumen improvement after ELCA (1.4 +/- 0.5 to 2.7 +/- 0.8 mm2) was the result of
      both tissue ablation (decrease in P+M CSA from 16.8 +/- 7.1 to 15.9 +/- 6.7 mm2,
      P < .0001) and vessel expansion (increase in EEM CSA from 18.2 +/- 7.1 to 18.6 +/
      6.8 mm2, P = .0245), with no change in calcium. The decrease in P+M CSA was 39%
      of the CSA of the laser catheter used. Dissections were present in 39% of
      lesions, 84% within superficial calcium; fibrocalcific deposits developed a
      "fragmented" appearance. CONCLUSIONS: ELCA increased lumen CSA by both
      atheroablation and vessel expansion without calcium ablation. Superficial
      fibrocalcific deposits developed a characteristic fragmented appearance. These
      findings support both photoablation and forced vessel expansion as mechanisms of
      lumen enlargement and plaque dissection after ELCA.

PMID- 8521562
TI  - Evaluation of importance of central effects of atenolol and metoprolol measured
      by heart rate variability during mental performance tasks, physical exercise, and
      daily life in stable postinfarct patients.
AB  - BACKGROUND: Physical exercise and mental work cause alterations in cardiac
      autonomic control. beta-Blockers protect the heart against stress, and this
      effect may be in part centrally mediated. In this context, the lipophilicity of
      the drug would be clinically relevant. METHODS AND RESULTS: Thirty postinfarct
      patients were randomized to receive 100 mg atenolol or 200 mg metoprolol CR in a
      double-blind, crossover manner, each for a 6-week period. Heart rate (HR)
      variability was used to study autonomic effects during mental and physical stress
      and to study circadian variations. Mean 24-hour HR decreased from 77 +/- 7 to 60
      +/- 6 beats per minute after atenolol and to 62 +/- 6 beats per minute after
      metoprolol (P = .046). At baseline, mental performance tasks did not affect HR,
      but decreased HR variability (SDNN index from 51 +/- 26 to 30 +/- 13 milliseconds
      [ms], P < .001; high-frequency power from 130 +/- 143 to 110 +/- 125 ms2, P =
      .046; and low-frequency power from 538 +/- 447 to 290 +/- 275 ms2, P < .001).
      Both beta-blockers decreased HR during mental performance tasks (P < .001) and
      increased SDNN index and high-frequency power. Before treatment, bicycle exercise
      decreased HR variability; root-mean-square of successive difference decreased
      from 21 +/- 8 to 15 +/- 10 ms (P = .004). beta-Blockade could not prevent this
      decrease. No differences between atenolol and metoprolol were observed for
      absolute high- and low-frequency power or after adjustment for HR. Vagal blockade
      with methylatropine during chronic beta-blocker treatment nearly abolished all
      components of spectral power. HR was found to be the parameter most strongly
      affected by beta-blockade but not by an influence on vagal tone. No differences
      were found between atenolol and metoprolol. CONCLUSIONS: In stable postinfarct
      patients, chronic treatment with metoprolol and atenolol attenuates the reduction
      in HR variability induced by mental performance tasks, but the effects during
      exercise are limited. beta-Blockers do not appear to increase vagal tone in this
      stable patient group. The point of action in these patients is mainly a reduction
      in HR, probably due to a reduction in stress-induced sympathetic activation.
      Clinically significant differences between atenolol and metoprolol were absent,
      indicating that the degree of lipophilicity does not distinguish among the beta
      blockers what their salutary effects are on HR variability during the specific
      challenges used.

PMID- 8521563
TI  - Role of endogenous bradykinin in human coronary vasomotor control.
AB  - BACKGROUND: Bradykinin is a potent vasodilator that acts through B2 kinin
      receptors to stimulate the release of endothelium-derived nitric oxide,
      prostacyclin, and hyperpolarizing factor. In this study, we investigated the
      contribution of endogenous bradykinin to vasomotor control in the human coronary
      circulation. METHODS AND RESULTS: The selective bradykinin B2 receptor antagonist
      HOE 140 was infused into the left main coronary artery (200 micrograms/min for 15
      minutes) in 15 patients without significant coronary stenoses. Epicardial
      responses were evaluated by quantitative coronary blood flow with a Doppler flow
      velocity wire. Flow-dependent dilation (n = 10; intracoronary papaverine) and
      acetylcholine responses (n = 5) were assessed before and after HOE 140. After HOE
      140, there was a reduction in luminal area in the proximal (P < .001), mid (P <
      .001), and distal (P < .05) coronary arteries. HOE 140 led to an increase in
      coronary vascular resistance (P < .001) and a decrease in coronary blood flow (P
      < .001). After bradykinin B2 receptor blockade, there was a reduction in flow
      dependent dilation (23.4 +/- 6.9% to 3.9 +/- 6.0%, P < .001), the extent of which
      correlated with the degree of basal vasoconstriction after HOE 140 in the same
      vessel segment (P < .05). Acetylcholine responses were unchanged after HOE 140.
      CONCLUSIONS: The results of this study demonstrate for the first time a role for
      endogenous bradykinin in mediating normal vasomotor responses in resistance and
      epicardial coronary vessels under basal and flow-stimulated conditions in the
      human coronary circulation.

PMID- 8521564
TI  - Modulation of endothelium-dependent flow-mediated dilatation of the brachial
      artery by sex and menstrual cycle.
AB  - BACKGROUND: Estrogen has been reported to augment endothelium-dependent
      vasodilatation. The role of endogenous ovarian hormones in modulating endothelium
      dependent vasodilatation, however, remains to be determined. The purpose of the
      present study was to investigate the effects of sex and menstrual cycle on
      endothelium-dependent flow-mediated vasodilatation. METHODS AND RESULTS:
      Seventeen female volunteers 25.1 +/- 0.8 years old and 17 age-matched male
      volunteers were examined. We measured brachial artery diameters noninvasively
      using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia, and after
      sublingual nitroglycerin administration. All female subjects were studied three
      times each, in three different phases of one menstrual cycle (M, menstrual phase;
      F, follicular phase; and L, luteal phase). Flow-mediated diameter (D) increase
      (%FMD; delta D/D x 100) in M, when serum estradiol level was low (121.9 +/- 12.5
      pmol/L), was 11.22 +/- 0.58%, and the value was comparable to that in male
      subjects (10.60 +/- 0.75%). %FMD increased in F (18.20 +/- 0.81%, P < .01 versus
      M) and L (17.53 +/- 0.74%, P < .01 versus M), when serum estradiol level was high
      (F, 632.0 +/- 74.5 and L, 533.8 +/- 33.4 pmol/L, P < .01 versus M). Endothelium
      independent vasodilatation by nitroglycerin increased in both F and L. However,
      the increment was smaller than that of %FMD. CONCLUSIONS: Endothelium-dependent
      vasodilatation varies during the menstrual cycle. The endogenous estradiol may be
      involved in this menstrual cycle-related vasodilatation.

PMID- 8521565
TI  - Quantitative relation between myocardial viability and improvement in heart
      failure symptoms after revascularization in patients with ischemic
      cardiomyopathy.
AB  - BACKGROUND: Studies of patients with coronary artery disease and left ventricular
      dysfunction have shown that preoperative quantification of myocardial viability
      may be clinically useful to identify those patients who will benefit most from
      revascularization both functionally and prognostically. However, the relation
      between preoperative extent of viability and change in heart failure symptoms has
      not been documented carefully. We assessed the relation between the magnitude of
      improvement in heart failure symptoms after coronary artery bypass surgery (CABG)
      and the extent of myocardial viability as assessed by use of quantitative
      analysis of preoperative positron emission tomography (PET) images. METHODS AND
      RESULTS: We studied 36 patients with ischemic cardiomyopathy (mean left
      ventricular ejection fraction, 28 +/- 6%) undergoing CABG. Preoperative extent
      and severity of perfusion abnormalities and myocardial viability (flow-metabolism
      mismatch) were assessed by use of quantitative analysis of PET images with 13N
      ammonia and fluorine-18-deoxyglucose. Each patient's functional status was
      determined before and after CABG by use of a Specific Activity Scale. Mean
      perfusion defect size and severity were 63 +/- 13% and 33 +/- 12%, respectively.
      Total extent of a PET mismatch correlated linearly and significantly with percent
      improvement in functional status after CABG (r = .87, P < .0001). A blood flow
      metabolism mismatch > or = 18% was associated with a sensitivity of 76% and a
      specificity of 78% for predicting a change in functional status after
      revascularization. Patients with large mismatches (> or = 18%) achieved a
      significantly higher functional status compared with those with minimal or no PET
      mismatch (< 5%) (5.7 +/- 0.8 versus 4.9 +/- 0.7 metabolic equivalents, P = .009).
      This resulted in an improvement of 107% in patients with large mismatches
      compared with only 34% in patients with minimal or no PET mismatch. CONCLUSIONS:
      In patients with ischemic cardiomyopathy, the magnitude of improvement in heart
      failure symptoms after CABG is related to the preoperative extent and magnitude
      of myocardial viability as assessed by use of PET imaging. Patients with large
      perfusion-metabolism mismatches exhibit the greatest clinical benefit after CABG.

PMID- 8521566
TI  - Prognostic importance of intimal thickness as measured by intracoronary
      ultrasound after cardiac transplantation.
AB  - BACKGROUND: Although intracoronary ultrasound (ICUS) has been validated for the
      early detection of transplant coronary artery disease (TxCAD), the prognostic
      importance of findings detected by this new imaging technique is unknown. METHODS
      AND RESULTS: This study examined the relation of clinical outcome in 145 heart
      transplant recipients (mean age, 45.1 +/- 11.1 years) with the amount of intimal
      thickness measured by ICUS during routine annual coronary angiography 1 to 10
      years (mean, 3.1 +/- 2.2 years) after transplantation. From published autopsy
      data, a mean intimal thickness of > 0.3 mm was considered significant. During a
      mean follow-up time of 48.2 +/- 10.2 months, 23 deaths (12 cardiac) occurred, and
      6 patients required retransplantation. Angiographic TxCAD developed in 22 of 125
      patients (17.6%) in the subgroup with normal angiograms at the time of ICUS and a
      follow-up annual angiographic study. In the total population and the subgroup,
      mean intimal thicknesses of > 0.3 and < or = 0.3 mm, respectively, were
      associated with significantly inferior 4-year actuarial overall survival (73%
      versus 96%, P = .005; 72% versus 92%, P = .05), cardiac survival (79% versus 96%,
      P = .005; 80% versus 98%, P = .04), and freedom from cardiac death and
      retransplantation (74% versus 98%, P < .0001; 70% versus 96%, P = .001). In
      addition, ICUS predicted freedom from development of subsequent angiographic
      TxCAD in the subgroup that was initially normal (26% versus 72%, P = .02). A mean
      intimal thickness by ICUS of > 0.3 mm was associated with inferior clinical
      outcome regardless of the presence of angiographic TxCAD and predicted the
      development of subsequent angiographic TxCAD. Despite significantly longer
      duration after transplantation, higher rejection incidence, and lower average
      daily cyclosporine dose, none of these covariates were independent risk factors
      for outcome. CONCLUSIONS: These findings confirm the prognostic importance of
      mean intimal thickening of > 0.3 mm in heart transplant recipients and suggest
      that these patients should be candidates for early interventional strategies.

PMID- 8521567
TI  - Dobutamine-atropine stress echocardiography in asymptomatic healthy individuals.
      The relativity of stress-induced hyperkinesia.
AB  - BACKGROUND: Interpretation of dobutamine-atropine stress echocardiography (DASE)
      is based on the assumption that the normal response to dobutamine-atropine
      infusion is characterized by increased systolic thickening and motion of the left
      ventricular (LV) walls, whereas a reduction or no change is considered indicative
      of coronary artery disease. The aim of this study was to quantitatively assess
      changes in LV dimension and wall motion patterns during DASE in a healthy
      population. METHODS AND RESULTS: Forty-two asymptomatic voluntary subjects (22
      men) with a mean age of 59 years (range, 31 to 79 years) and a likelihood of < 5%
      for coronary artery disease underwent DASE with digital recording of two
      dimensional and M-mode echocardiography at baseline and low-dose and peak
      infusion rates. Mean end-diastolic and end-systolic LV diameters and areas
      decreased and wall thicknesses increased progressively throughout the test. Wall
      motion and thickening increased from baseline to low-dose infusion in nearly all
      subjects. However, from low-dose to peak infusion, the mean absolute wall motion
      and relative wall thickening decreased by 13.1% (95% CI, 2.7 to 23.5) and 21.4%
      (95% CI, 6.4 to 36.4) regardless of age, sex, or use of atropine. Changes in
      fractional shortening and absolute wall thickening varied considerably, with a
      decrease observed in 15 and 13 individuals (36% and 31%), respectively.
      CONCLUSIONS: In healthy subjects, measures of wall motion and wall thickening
      increased from baseline to low-dose infusion but decreased from low-dose to peak
      infusion. These findings call for revision of the assumptions on which the common
      analysis of DASE is based.

PMID- 8521568
TI  - Pressure recovery in bileaflet heart valve prostheses. Localized high velocities
      and gradients in central and side orifices with implications for Doppler-catheter
      gradient relation in aortic and mitral position.
AB  - BACKGROUND: We investigate pressure recovery in central and side orifices of St
      Jude valves and the effect of mitral versus aortic position on the relation
      between Doppler- and catheter-derived pressure gradients. METHODS AND RESULTS:
      Maximum, transvalvular, and net pressure gradients are calculated and compared
      with Doppler-derived gradients in an in vitro model. Pressure recovery and
      pressure loss coefficients are calculated. Simultaneous Doppler and catheter
      gradients are obtained intraoperatively in five patients undergoing mitral valve
      replacement. Centerline Doppler gradients correspond closely with maximum
      catheter gradients but are higher than transvalvular and net pressure gradients.
      Thirty-six percent of the initial pressure drop is recovered between the valve
      leaflets and is independent of valve size or configuration. A variable amount of
      postvalvular pressure recovery is observed depending on aortic or mitral
      configuration. Side orifice velocities are 85 +/- 4% of the centerline
      velocities. Incorporation of the pressure loss coefficient in the simplified
      Bernoulli equation shows close agreement between centerline Doppler gradients and
      transvalvular gradients (r = .99, y = 1.11x-0.19). CONCLUSIONS: Gradients across
      the St Jude valve measured by Doppler ultrasound are higher than transvalvular or
      net catheter gradients due to downstream pressure recovery. This is more marked
      for Doppler gradients based on centerline velocities than side orifice velocities
      and is more pronounced for valves in an aortic than a mitral configuration.
      Therefore, to be comparable with invasive transvalvular catheter gradients,
      either Doppler gradients should be calculated based on side orifice velocity
      measurements or the Doppler gradient calculation should include the pressure loss
      coefficient when based on central orifice velocities.

PMID- 8521569
TI  - Imaging and sizing of atrial septal defects by magnetic resonance.
AB  - BACKGROUND: Development of techniques for percutaneous closure of atrial septal
      defects (ASDs) makes accurate noninvasive sizing of ASDs important for
      appropriate patient selection. METHODS AND RESULTS: Magnetic resonance (MR)
      images of ASDs were obtained in 30 patients (mean age, 41 +/- 16 years) by both
      spin-echo and phase-contrast cine MR imaging. Spin-echo images were obtained in
      two orthogonal views (short-axis and four-chamber) perpendicular to the plane of
      the ASD. Spin-echo major and minor diameters were measured, and spin-echo defect
      area was calculated. Phase-contrast cine MR images were obtained in the plane of
      the ASD, and cine major diameter and defect area were measured from the region of
      signal enhancement or phase change due to shunt flow across the defect. MR
      measurements were compared with templates cut during surgery to match the defect
      or with ASD diameter determined by balloon sizing at catheterization. ASD size
      measured from cine MR images (y) agreed closely with catheterization and template
      standards (x). For major diameter, y = 0.78x + 5.7, r = .93, and SEE = 3.4 mm. On
      average, spin-echo measurements overestimated major diameter and area of secundum
      ASDs by 48% and 125%, respectively. CONCLUSIONS: Phase-contrast cine MR images
      acquired in the plane of an ASD define the defect shape by the cross section of
      the shunt flow stream and allow noninvasive determination of defect size with
      sufficient accuracy to permit stratification of patients to closure of the defect
      by catheter-based techniques versus surgery. Spin-echo images, on the other hand,
      are not adequate for defining ASD size, because septal thinning adjacent to a
      secundum ASD may appear to be part of the defect.

PMID- 8521570
TI  - Catheter ablation of the mitral isthmus for ventricular tachycardia associated
      with inferior infarction.
AB  - BACKGROUND: Intraoperative mapping studies suggest that an isthmus of myocardium
      between the mitral valve annulus and the border of inferior myocardial infarction
      may play a role in the genesis of ventricular tachycardia. We examined the
      frequency with which a slow conduction zone within the mitral isthmus was
      critical to the maintenance of ventricular tachycardia associated with remote
      inferior infarction in patients undergoing catheter ablation. METHODS AND
      RESULTS: In 4 of 12 patients, a critical zone of slow conduction was identified
      within the mitral isthmus. In each of these patients, two characteristic and
      morphologically distinct tachycardias were induced: a left bundle (rS in V1, R in
      V6), left superior axis morphology and a right bundle (R in V1, QS in V6), right
      superior axis morphology (cycle length, 610 to 320 ms). In each patient, a zone
      of slow conduction, shared by both morphologies, was characterized by diastolic
      potentials with electrogram-QRS intervals of 85 to 161 ms (21% to 47% of
      tachycardia cycle length) and entrainment with concealed fusion during pacing
      associated with stimulus-QRS intervals of 81 to 400 ms (20% to 91% of tachycardia
      cycle length). In each patient, a single radiofrequency energy application at the
      shared site of slow conduction eliminated inducibility of both morphologies.
      During follow-up of 1 to 11 months, no patient had recurrent tachycardia.
      CONCLUSIONS: The mitral isthmus contains a critical region of slow conduction in
      some patients with ventricular tachycardia after inferior myocardial infarction,
      providing a vulnerable and anatomically localized target for catheter ablation.
      Characteristic tachycardia morphologies may provide clinical markers for this
      underlying mechanism.

PMID- 8521571
TI  - Prediction of atrioventricular block during radiofrequency ablation of the slow
      pathway of the atrioventricular node.
AB  - BACKGROUND: Selective radiofrequency (RF) ablation of the slow pathway is an
      effective treatment for atrioventricular (AV) nodal reentry tachycardia. A
      previous report showed that rapid junctional tachycardia (JT) caused by RF
      associated with loss of ventriculoatrial (VA) conduction is related to increased
      risk for AV block. However, this can be difficult to detect during energy
      delivery, and more importantly, it cannot be measured before the onset of RF
      energy delivery. The aim of our study was to determine whether measurements made
      from electrograms could be used to predict the risk of AV block before RF energy
      is delivered. METHODS AND RESULTS: Fifty-eight patients underwent 63 selective
      slow pathway RF ablation procedures. In 46 (26.9%) of 172 JTs caused by RF, VA
      block was observed, and in 11 this was followed by AV block of various degrees.
      Electrograms before each application of RF were analyzed for the interval between
      the atrial signals in the His bundle catheter and in the distal mapping catheter
      [A(H)-A(Md)], the interval between the atrial signals in the His bundle catheter
      and in the proximal coronary sinus catheter [A(H)-A(CS)], the AV ratio, and the
      presence of a slow pathway potential or a fractionated atrial signal in the
      distal mapping catheter. Mean cycle length (CL) of JT was calculated if it
      consisted of at least 10 beats. These parameters were compared between patients
      with JT who developed VA block and subsequent AV block (group 1), patients with
      JT and VA block but without subsequent AV block (group 2), and patients with JT
      without VA block (group 3). The A(H)-A(Md) interval was significantly shorter in
      group 1 (17 +/- 8 ms) than in groups 2 (33 +/- 8 ms, P < .001) and 3 (32 +/- 10
      ms, P < .001), whereas the A(H)-A(Md) intervals of groups 2 and 3 did not differ
      from each other. CL of JT, A(H)-A(CS) interval, AV ratio, presence of a slow
      pathway potential, or a fractionated atrial electrogram were not related to the
      occurrence of AV block. CONCLUSIONS: The A(H)-A(Md) interval provides an
      electrophysiological marker that can be used in addition to the radiological
      catheter position to assess the risk for AV block before onset of RF delivery. CL
      of JT and occurrence of VA block are not related to the risk of AV block.

PMID- 8521572
TI  - Delayed rectifier channels in human ventricular myocytes.
AB  - BACKGROUND: Previous studies have shown that in heart there are two kinetically
      distinct components of delayed rectifier current: a rapidly activating component
      (IKr) and a more slowly activating component (IKs). The presence of IKr and/or
      IKs appears to be species dependent. We studied the nature of the delayed
      rectifier current in human ventricle in whole-cell and single-channel
      experiments. METHODS AND RESULTS: Ventricular myocytes were obtained from hearts
      of patients with ischemic or dilated cardiomyopathy. Single-channel currents and
      whole-cell tail currents were recorded at negative potentials directly after
      return from a depolarizing step. Single-channel currents were measured in the
      cell-attached patch configuration with 140 mmol/L K+ in the pipette. In the
      present study, we identified a voltage-dependent channel with a single-channel
      conductance of 12.9 +/- 0.8 pS (mean +/- SEM, n = 5) and a reversal potential
      near to the K+ equilibrium potential, suggesting that the channel is selective to
      K+ ions. Channel activity was observed only after a depolarizing step and
      increased with the duration and amplitude of the depolarization, indicating time-
      and voltage-dependent activation. Activation at +30 mV was complete within 300
      milliseconds, and the time constant of activation, determined in the whole-cell
      configuration, was 101 +/- 25 milliseconds (mean +/- SEM, n = 4). The voltage
      dependence of activation could be described by a Boltzmann equation with a half
      activation potential of -29.9 mV and a slope factor of 9.5 mV. The addition of
      the class III antiarrhythmic drug E-4031 completely blocked channel activity in
      one patch. No indications for the presence of IKs were found in these
      experiments. CONCLUSIONS: The conformity between the properties of IKr and those
      of the K+ channel in the present study strongly suggests that IKr is present in
      human ventricle.

PMID- 8521573
TI  - Nitric oxide. An important signaling mechanism between vascular endothelium and
      parenchymal cells in the regulation of oxygen consumption.
AB  - BACKGROUND: Nitric oxide (NO) is known to be an inhibitor of mitochondrial
      function. However, the physiological significance of endothelium-derived NO in
      the control of tissue respiration is not established. METHODS AND RESULTS: Tissue
      O2 consumption by skeletal muscle slices of the triceps brachii of normal dogs
      was measured with a Clark-type O2 electrode/tissue bath system at 37 degrees C. S
      Nitroso-N-acetylpenicillamine (SNAP), carbachol (CCh), or bradykinin (BK)
      decreased tissue O2 consumption by 12 +/- 3% to 55 +/- 8%, 15 +/- 6% to 36 +/-
      11%, or 21 +/- 5% to 42 +/- 4% at doses of 10(-7) to 10(-4) mol/L, respectively.
      The effects of both CCh and BK but not SNAP were eliminated by nitro-L-arginine
      (NLA, 10(-4) mol/L), consistent with SNAP decomposing to release NO and both CCh
      and BK stimulating endogenous NO production from L-arginine. Oxygen consumption
      was also decreased by 8-bromo-cGMP. The mitochondrial uncoupler dinitrophenol
      blocked the effects of 8-bromo-cGMP but only slightly altered those of SNAP,
      indicating that the major site of action of NO is the mitochondria. In normal,
      chronically instrumented, resting conscious dogs, blockade of NO synthase by NLA
      increased mean arterial pressure by 28 +/- 2.5 mm Hg and hind limb vascular
      resistance by 114 +/- 12% and decreased blood flow by 39 +/- 3%. Most important,
      NLA also increased O2 uptake by 55 +/- 9% in hind limb skeletal muscle (P < .05),
      associated with decreases in PO2 and O2 saturation and an increase in reduced
      hemoglobin in hind limb venous blood. CONCLUSIONS: Our results indicate that NO
      release from vascular endothelial cells appears to play an important
      physiological role in the regulation of tissue mitochondrial respiration in
      skeletal muscle and perhaps other organ systems.

PMID- 8521574
TI  - Exposure to shear stress alters endothelial adhesiveness. Role of nitric oxide.
AB  - BACKGROUND: Shear stress increases the release of nitric oxide (NO) by
      endothelial cells (ECs). We and others have provided evidence that endothelium
      derived NO inhibits monocyte adhesion to the vessel wall. We therefore
      hypothesized that previous exposure to shear stress would inhibit endothelial
      adhesiveness for monocytes by virtue of its effect to increase NO release.
      METHODS AND RESULTS: Confluent monolayers of bovine aortic endothelial cells,
      human aortic endothelial cells, or human venous endothelial cells were exposed to
      laminar fluid flow. Culture media were collected for measurement of NO (by
      chemiluminescence) and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha.
      NOx and 6-keto-prostaglandin F1 alpha accumulated in the conditioned medium
      during laminar fluid flow from 30 minutes to 24 hours in a time-dependent
      fashion. In another set of studies, ECs previously exposed to flow or to static
      conditions were washed with Hanks' buffer and exposed to THP-1 cells for 30
      minutes. Adherent cells were counted by microscopy. Previous exposure to flow
      reduced endothelial adhesiveness for monocytes by 50% (P < .05). The effect of
      flow on endothelial adhesiveness occurred within 30 minutes. This effect was
      abrogated by nitro-L-arginine (an antagonist of NO synthesis), as well as by
      tetraethylammonium ion (an antagonist of the flow-activated potassium channel);
      the effects of these inhibitors were reversed by the NO donor SPM-5185. Although
      the cyclo-oxygenase inhibitor indomethacin totally inhibited the flow-induced
      production of prostacyclin by ECs, it minimally affected adherence of THP-1
      cells. The early effect of flow on endothelial adhesiveness was not mediated by
      alterations in the expression of the endothelial adhesion molecules VCAM-1 or
      ICAM-1 as assessed by fluorescent activated cell sorting. CONCLUSIONS: Shear
      stress alters endothelial adhesiveness for monocytes; at early time points, this
      effect is largely due to flow-stimulated release of NO and, to a lesser extent,
      prostacyclin. This effect of flow occurs within 30 minutes and is probably due to
      alterations in the signal transduction or activation state (rather than the
      expression) of endothelial adhesion molecules.

PMID- 8521575
TI  - Lysophosphatidylcholine inhibits endothelium-dependent hyperpolarization and N
      omega-nitro-L-arginine/indomethacin-resistant endothelium-dependent relaxation in
      the porcine coronary artery.
AB  - BACKGROUND: Oxidized LDL and lysophosphatidylcholine (LPC) have been reported to
      inhibit the endothelium-dependent relaxation (EDR) mediated by nitric oxide.
      Recently, a new vasorelaxing factor, endothelium-derived hyperpolarizing factor
      (EDHF), which hyperpolarizes and relaxes the porcine coronary artery in the
      presence of N omega-nitro-L-arginine (NNA) and indomethacin (IM), has been
      reported. We examined whether LPC also inhibits both the EDHF-mediated relaxation
      and membrane hyperpolarization of the porcine coronary artery. METHODS AND
      RESULTS: EDHF was evaluated as the bradykinin- or A23187-induced relaxation of
      the porcine coronary artery contracted by prostaglandin F2 alpha in the presence
      of NNA and IM. We also directly measured the membrane potential of the porcine
      coronary artery. The effects of LPC on both relaxation and membrane
      hyperpolarization were investigated. At concentrations of 0 to 20 mumol/L, LPC
      dose-dependently inhibited the NNA/IM-resistant EDR induced by bradykinin and
      A23187, and the relaxation was reversible after the absorption of LPC with
      albumin. LPC also inhibited the bradykinin- and A23187-induced hyperpolarization
      of the porcine coronary artery. CONCLUSIONS: In the present study, LPC was found
      to inhibit not only nitric oxide-mediated but also EDHF-mediated relaxation of
      the porcine coronary artery. Our findings suggest a new regulatory mechanism in
      the atherosclerotic coronary artery.

PMID- 8521576
TI  - 31P nuclear magnetic resonance spectroscopic imaging of regions of remodeled
      myocardium in the infarcted rat heart.
AB  - BACKGROUND: The clinical course of a patient with a myocardial infarction (MI)
      depends largely on the ability of the noninfarcted region to remodel and
      compensate for the loss of the infarcted region. Previous studies have shown that
      the remaining viable myocardium remodels morphologically, functionally, and
      biochemically. The purpose of this study was to define the regional distribution
      of the biochemical remodeling that occurs after MI in rat hearts by use of a
      technique that could be applied noninvasively to human subjects. METHODS AND
      RESULTS: Infarcts of the left ventricular apex and anterolateral wall were
      induced by occluding a coronary artery. Eight to 10 weeks after infarction, one
      dimensional chemical shift imaging (CSI) was used to obtain 31P nuclear magnetic
      resonance (NMR) spectra of eight 2.5-mm-thick cross-sectional slices along the
      long axis (from base to apex) of isolated buffer-perfused rat hearts. Regional
      ATP and phosphocreatine (PCr) contents were compared in remodeled versus normal
      (sham) myocardium. Spin-echo 1H MR images identified the mass of each slice,
      allowing calculations of metabolite amount per unit myocardium in each slice. 1H
      MR images identify the hypertrophy of remodeled myocardium but do not
      discriminate between scar and viable tissue. In contrast, 31P CSI does
      distinguish viable tissue. Compared with shams, there was less 31P signal in the
      slices distal to the occlusion containing mainly scar tissue and increased signal
      intensity in slices proximal to the occlusion because of myocyte hypertrophy. The
      ATP signal intensity changed in direct proportion to the viable tissue mass in
      the slice, suggesting that the amount of ATP per unit mass in viable remodeled
      myocardium is the same as that of the shams. In contrast, the amount of PCr per
      unit mass in remodeled myocardium decreased. This decrease is uniform across the
      slices, correlates with infarct size, and parallels a similar decrease in tissue
      creatine content. CONCLUSIONS: 31P CSI of post-MI hearts shows that (1) PCr
      decreases uniformly (ie, independent of the distance from the scar) in the
      noninfarcted remodeled myocardium, and its amount inversely correlates with
      infarct size; and (2) the ATP signal provides a profile of viable myocardium and
      is a biochemical marker of morphological remodeling and hypertrophy that has
      occurred in noninfarcted regions. Thus, 31P CSI provides both a marker that
      tissue injury has occurred (decreased PCr) and a marker of the extent of
      remodeling in response to injury (ATP distribution) in a single set of
      noninvasive measurements.

PMID- 8521577
TI  - Effects of ischemia on left ventricular apex rotation. An experimental study in
      anesthetized dogs.
AB  - BACKGROUND: Left ventricular (LV) twist has been defined as the counterclockwise
      rotation of the ventricular apex with respect to the base during systole. We
      recently showed that, since base rotation is minimal, measurement of apex
      rotation reflects the dynamics of LV twist. Since ischemia is known to affect
      endocardial and epicardial fiber force and shortening and therefore the
      transmural balance of torsional moments, we hypothesized that ischemia has a
      significant effect on apex-rotation amplitude and on untwisting during the
      isovolumic relaxation (IVR) period. METHODS AND RESULTS: With an optical device
      coupled to the LV apex, apex rotation was recorded simultaneously with LV
      pressure, ECG, LV segment length, and minor-axis diameters in 16 open-chest dogs.
      Ischemia was caused by a 1- to 2-minute snare occlusion of either the left
      anterior descending (LAD) or circumflex (LCx) arteries. LAD ischemia had a
      pronounced effect on apex rotation: an increase in apex-rotation amplitude
      attributed to subendocardial dysfunction at 10 seconds of ischemia; maximum apex
      rotation occurring later (during the IVR period) throughout the ischemia; a
      paradoxical relaxation pattern of initial untwisting followed by twisting and
      untwisting during the IVR period with ischemia; and a decrease in the amplitude
      of apex rotation with ischemia, possibly due to transmural dysfunction. LCx
      occlusion had similar effects on apex rotation, except that apex-rotation
      amplitude was not increased at 10 seconds of occlusion and the amplitude of apex
      rotation did not decrease with severe ischemia. Under control preischemic
      conditions, a linear relationship between apex rotation and segment length was
      observed during ejection and a different, steeper relationship during IVR. With
      regionally ischemic segments, this relationship became nonlinear for both
      ejection and IVR. CONCLUSIONS: Both LAD and LCx ischemia had profound effects on
      the dynamics of apex rotation. A paradoxical relaxation pattern occurred with
      ischemia. We suggest that these observations are due to changes in the dynamic
      transmural balance of torsional moments that determine LV twist.

PMID- 8521578
TI  - In vivo MRI visualization of acute myocardial ischemia and reperfusion in ferrets
      by the persistent action of the contrast agent Gd (BME-DTTA).
AB  - BACKGROUND: Contrast agent-enhanced magnetic resonance imaging (MRI) has the
      potential to visualize myocardial ischemia. To date, however, no agent has been
      found that has a sustained effect that allows MRI detection for the entire
      duration of ischemia and reperfusion and thus is useful in conjunction with
      stress test MRI. In this article, we introduce the gadolinium complex of N3,N6
      bis(2'-myrisotyloxyethyl)-1,8-dioxo-triethylene- tetraamine-N,N,N1,N1-tetraacetic
      acid [Gd(BME-DTTA)], an agent potentially useful for such a purpose. METHODS AND
      RESULTS: Four protocols were carried out. ECG-triggered, partially T1-weighted,
      spin-echo MRI was used in protocols A through C. In protocol A, in nonischemic
      ferrets, 50 mumol/kg Gd(BME-DTTA) induced a 70 +/- 5% intensity enhancement
      lasting 3 hours. In protocol B, the left anterior descending coronary artery was
      occluded, and a 99mTc-sestamibi-induced autoradiographic contrast verified (r =
      .87, P < .01) a Gd(BME-DTTA)-induced (n = 5) or Gd(DTPA)-induced (n = 4) MRI
      contrast. In the Gd(BME-DTTA) group a sustained contrast and in the Gd(DTPA)
      group a short-lived contrast were observed. In protocol C (n = 11), during
      ischemia, a 31 +/- 3.3% (P < .02) contrast was evident between the ischemic and
      nonischemic myocardial regions. Upon reperfusion, a contrast of 19 +/- 3% (P <
      .05) and 13 +/- 4.5% (P < .05) persisted for 5 and 15 minutes, respectively.
      Beyond 15 minutes, the contrast continued to diminish gradually. Nonradioactive
      microspheres verified (r = .87, P < .05) ischemia and reperfusion in this model.
      In protocol D (n = 4), blood delta R1 data showed that the blood pool retained
      Gd(BME-DTTA) for the entire time frame of the experiment at high enough
      concentration to provide an appropriate wash-in effect during the initial
      contrast enhancement and during reperfusion. CONCLUSIONS: This study demonstrates
      that Gd(BME-DTTA) induces a sustained MRI contrast between regions of normal
      versus ischemic myocardium, showing the potential of this agent for the diagnosis
      of ischemic heart disease in conjunction with stress tests.

PMID- 8521579
TI  - Loading sequence plays an important role in enhanced load sensitivity of left
      ventricular relaxation in conscious dogs with tachycardia-induced cardiomyopathy.
AB  - BACKGROUND: Left ventricular relaxation rate in the failing heart depends more on
      the systolic load than in the normal heart. To elucidate the mechanisms for the
      enhanced load sensitivity of left ventricular relaxation in heart failure, we
      examined the relative contributions of changes in end-systolic volume and loading
      sequence to the left ventricular relaxation rate. METHODS AND RESULTS: In seven
      conscious dogs, the time constant (Td) of left ventricular pressure decay, end
      systolic volume, systolic circumferential force, and time to peak force during
      caval occlusion were compared before and after development of tachycardia-induced
      heart failure. Rapid ventricular pacing decreased the slope of the end-systolic
      pressure-volume relation from 4.5 to 2.8 mm Hg/mL (P < .01) and prolonged Td from
      33 to 49 ms (P < .01). In normal conditions, caval occlusion reduced end-systolic
      force (-580 g, P < .01) and end-systolic volume (-7 mL, P < .01) but did not
      change Td or time to peak force. In heart failure, however, caval occlusion
      shortened Td (-11 ms, P < .01), with a concomitant decrease in the time to peak
      force (-30 ms, P < .01), while end-systolic volume and force declined slightly.
      Consequently, for a comparable reduction in end-systolic force, Td decreased more
      in heart failure than in normal hearts, suggesting enhanced load sensitivity.
      Moreover, changes in Td correlated well with those in the time to peak force (r =
      .79, P < .01) but not with those in end-systolic volume. CONCLUSIONS: Loading
      sequence rather than elastic recoil seems to play the predominant role in the
      enhanced load sensitivity of left ventricular relaxation in heart failure.

PMID- 8521580
TI  - Effects of ACE inhibitors on circulating versus cardiac angiotensin II in volume
      overload-induced cardiac hypertrophy in rats.
AB  - BACKGROUND: Cardiac volume overload by an aortocaval shunt increases left
      ventricular end-diastolic pressure (LVEDP) and plasma and cardiac renin activity
      and results in LV hypertrophy. To a similar extent, the angiotensin-converting
      enzyme (ACE) inhibitors enalapril and quinapril prevent the increase in LVEDP.
      However, only quinapril attenuates the development of LV hypertrophy. We
      hypothesize that a low affinity of enalapril for cardiac ACE results in
      continuing generation of cardiac angiotensin II and thus hypertrophic growth of
      cardiomyocytes. METHODS AND RESULTS: In the present study, we assessed plasma and
      cardiac angiotensins I and II 1 and 7 days after aortocaval shunt and the effects
      of enalapril and quinapril started 3 days before surgery on plasma and cardiac
      angiotensin I and II at the same time points. Aortocaval shunt increased plasma
      angiotensin II at 1 day by 180%, but only a small increase (by 40%) persisted at
      7 days. Aortocaval shunt increased LV angiotensin II by 100% and 65% at 1 and 7
      days, respectively. Both blockers similarly prevented the increase in plasma
      angiotensin II by aortocaval shunt at both time points. In contrast, only
      quinapril prevented the rise in LV angiotensin II induced by shunt at 1 and 7
      days. CONCLUSIONS: Aortocaval shunt increases LVEDP and plasma and cardiac
      angiotensin II and results in LV hypertrophy. Only prevention of the increase in
      LVEDP and in plasma and cardiac angiotensin II attenuates the development of LV
      hypertrophy, consistent with the concept that angiotensin II is involved in the
      development of cardiac hypertrophy by aortocaval shunt by both hemodynamic and
      cardiac trophic effects. This study is the first to show that differences in
      affinity for cardiac ACE may determine the effect of ACE inhibitors on cardiac
      angiotensin II and therefore cardiac hypertrophy.

PMID- 8521581
TI  - Images in cardiovascular medicine. Adult congenital heart disease. Obstructive
      and nonobstructive cor triatriatum.

PMID- 8521582
TI  - Early and 1-year clinical outcome of patients evolving non-Q-wave versus Q-wave
      myocardial infarction after thrombolysis: results from the TIMI II study.

PMID- 8521583
TI  - Sex differences in mortality after myocardial infarction: is there evidence for
      an increased risk for women?

PMID- 8521584
TI  - Idiopathic hypereosinophilic vasculitis.

PMID- 8521585
TI  - Scopolamine and heart rate variability.

PMID- 8521586
TI  - Exercise standards.

PMID- 8521587
TI  - Geometric remodeling.

PMID- 8521588
TI  - Lipoprotein(a), ACE, and family history of CAD.

PMID- 8521589
TI  - Selection and treatment of candidates for heart transplantation. A statement for
      health professionals from the Committee on Heart Failure and Cardiac
      Transplantation of the Council on Clinical Cardiology, American Heart
      Association.
AB  - Improved outcome of heart failure in response to medical therapy, coupled with a
      critical shortage of donor organs, makes it imperative to restrict heart
      transplantation to patients who are most disabled by heart failure and who are
      likely to derive the maximum benefit from transplantation. Hemodynamic and
      functional indexes of prognosis are helpful in identifying these patients.
      Stratification of ambulatory heart failure patients by objective criteria, such
      as peak exercise oxygen consumption, has improved ability to select appropriate
      adult patients for heart transplantation. Such patients will have a poor
      prognosis despite optimal medical therapy. When determining the impact of
      individual comorbid conditions on a patient's candidacy for heart
      transplantation, the detrimental effects of each condition on posttransplantation
      outcome should be weighed. Evaluation of patients with severe heart failure
      should be done by a multidisciplinary team that is expert in management of heart
      failure, performance of cardiac surgery in patients with low left ventricular
      ejection fraction, and transplantation. Potential heart transplant candidates
      should be reevaluated on a regular basis to assess continued need for
      transplantation. Long-term management of heart failure should include continuity
      of care by an experienced physician, optimal dosing in conventional therapy, and
      periodic reevaluation of left ventricular function and exercise capacity. The
      outcome of high-risk conventional cardiovascular surgery should be weighed
      against that of transplantation in patients with ischemic and valvular heart
      disease. Establishment of regional specialized heart failure centers may improve
      access to optimal medical therapy and new promising medical and surgical
      treatments for these patients as well as stimulate investigative efforts to
      accelerate progress in this critical area.

PMID- 8521590
TI  - Screening for cancer in high risk families.
AB  - OBJECTIVE: To review screening for cancer in high risk families. METHODS AND
      RESULTS: Screening for hereditary cancer involves three steps: it is first
      necessary to identify families at high risk by examining the number and sites of
      cancer in a family. Special attention is given to cancers appearing at an early
      age, to unusual sites, and multiple primary cancers. Second, a molecular
      diagnostic test is performed in order to identify family members who carry a
      mutant copy of the suspected gene. DNA-based diagnostic testing is now available
      for hereditary breast-ovarian cancer, for hereditary nonpolyposis colon cancer,
      for Gardner syndrome (familial polyposis coli), for neurofibromatosis, multiple
      endocrine neoplasia, and for Von-Hippel Lindau disease. Third, individuals found
      to carry susceptibility genes are offered screening for the early detection of
      tumours. Some screening methods are in conventional use (e.g., colonoscopy and
      mammography); others are reserved for the investigation of familial cancers
      (e.g., pentagastrin challenge test). CONCLUSION: A comprehensive clinic for
      hereditary cancer must consider all three phases of the screening program and
      will provide expert genetic counselling to family members involved in the
      process.

PMID- 8521591
TI  - Use of artificial intelligence in analytical systems for the clinical laboratory.
AB  - OBJECTIVE: To consider the role of software in system operation, control and
      automation, and attempts to define intelligence. METHODS AND RESULTS: Artificial
      intelligence (Al) is characterized by its ability to deal with incomplete and
      imprecise information and to accumulate knowledge. Expert systems, building on
      standard computing techniques, depend heavily on the domain experts and knowledge
      engineers that have programmed them to represent the real world. Neural networks
      are intended to emulate the pattern-recognition and parallel processing
      capabilities of the human brain and are taught rather than programmed. The future
      may lie in a combination of the recognition ability of the neural network and the
      rationalization capability of the expert system. In the second part of this
      paper, examples are given of applications of Al in stand-alone systems for
      knowledge engineering and medical diagnosis and in embedded systems for failure
      detection, image analysis, user interfacing, natural language processing,
      robotics and machine learning, as related to clinical laboratories. CONCLUSION:
      Al constitutes a collective form of intellectual property, and that there is a
      need for better documentation, evaluation and regulation of the systems already
      being used widely in clinical laboratories.

PMID- 8521592
TI  - Pseudohyperphosphatemia.
AB  - OBJECTIVE: To review instances of spurious elevation of inorganic phosphate
      measurements due to interference with analytical methods. METHODS: SElective
      literature review. RESULTS: Depending on the method used to measure inorganic
      phosphate, several factors have been reported to produce spurious elevations,
      including paraproteinemia, hyperlipidemia, hemolysis, and hyperbilirubinemia. Of
      these, paraproteinemia is probably the commonest. CONCLUSION: Both clinical
      biochemists and clinicians should be aware of the phenomenon of
      pseudohyperphosphatemia. Clinically unexplained persistent hyperphosphatemia
      should initiate a search for potential causes of pseudohypophosphatemia,
      especially paraproteinemia.

PMID- 8521593
TI  - Development of an enzyme-linked immunosorbent assay for 2,3-dinor-6-keto
      prostaglandin F1 alpha in urine using a monoclonal antibody.
AB  - OBJECTIVES: To develop and validate an enzyme-linked immunosorbent assay (ELISA)
      for measurement of urinary 2,3-dinor-6-keto-prostaglandin F1 alpha (2,3D6KPGF1
      alpha) using a monoclonal antibody and a horseradish peroxidase-linked antigen.
      DESIGN AND METHODS: Assay validation included optimization of the standard curve,
      antibody cross-reactivity, accuracy and imprecision studies together with
      preliminary measurement of clinical samples. RESULTS: Optimal conditions of the
      standard curve (0.078-10.0 micrograms/L) used 2 mg/L of antibody and 3
      micrograms/L of peroxidase conjugate in each well, at pH 7.2. The coefficient of
      variation of various concentrations of the standard curve averaged 6.8%. Antibody
      cross-reactivity was < 0.01% for related prostanoids. Recovery of known amounts
      (0.1-5.0 micrograms/L) of 2,3D6KPGF1 alpha added to an urinary sample was 101.2
      +/- 6.3%. Imprecision studies with non-pregnant (0.24 microgram/L) and pregnant
      (2.5 micrograms/L) samples displayed an intraassay variability of 8.9 and 9.9%,
      and an interassay variability of 9.6 and 10.0%, respectively. Urinary
      measurements in the non-pregnant and pregnant states were similar to those
      previously reported. An apparent decreased concentration was observed early in
      pregnancy in future preeclampsia. CONCLUSION: With similar precision and
      validity, our assay method is time- and cost-saving. Preliminary urinary
      measurements show that this analyte may be of interest as an early marker for
      preeclampsia.

PMID- 8521594
TI  - A rapid gas-liquid chromatography method for the determination of lactulose and
      mannitol in urine: clinical application in studies of intestinal permeability.
AB  - OBJECTIVE: The purpose of this study was to develop a gas-liquid chromatography
      method for the determination of the urinary excretion of two nonmetabolizable
      sugars (lactulose and mannitol) to estimate the intestinal permeability. METHODS:
      Two internal standards (alpha-methyl-D-glucopyranosyde and sucrose) were added to
      the urine samples prior to derivatization with the aid of a solution of pyridine,
      [N, O-bis (trimethylsilyl)]-acetamide and chlorotrimethylsilan. Sample
      preparation was simpler and faster than in other previous methods and the four
      sugars were resolved within 27 min. RESULTS: The inclusion of internal standards
      reduced the coefficient of variation from 9.44% to 4.78%. The method provided
      better sensitivity, range of analysis, and linearity than a previously published
      HPLC method reducing variances in the recovery of lactulose and mannitol added to
      urine. The clinical application of this method was tested in preterm infants fed
      human milk or cow's milk based formula and in breast fed term infants.
      CONCLUSION: The method described here for the determination of urinary lactulose
      and mannitol is more rapid, simpler, and more accurate than other previously
      published methods.

PMID- 8521595
TI  - An ultrasensitive immunoassay for prostate-specific antigen based on conventional
      colorimetric detection.
AB  - OBJECTIVE: Development of an ultrasensitive immunoassay for serum PSA involving
      conventional detection probes. DESIGN AND METHODS: The assay involves a
      polyclonal antibody immobilized in microtitration wells and a monoclonal antibody
      labeled with horseradish peroxidase. In a one-step assay, the enzymatic activity
      of the bound detection antibody is monitored by the addition of hydrogen
      peroxide/tetramethylbenzidine substrate reagent followed by spectrophotometric
      quantification of the conversion product. RESULTS: The assay has a lower
      detection limit of 0.003 micrograms/L, biological detection limit of 0.009
      micrograms/L, and intra- and interassay CVs of 8.2% and 10.5% at PSA
      concentrations of 0.022 and 0.065 micrograms/L, respectively. The recovery of the
      assay averaged 104% and it demonstrated a dilution linearity down to at least
      0.01 micrograms of PSA/L. Results of comparison data correlated well with those
      obtained by a well established enzyme immunoassay. The serum PSA concentrations
      were < 0.012 micrograms/L in the majority of patients (53.8%) who had undergone
      radical prostatectomy. CONCLUSIONS: This assay is well suited for post-surgical
      monitoring of PSA in patients with prostate cancer.

PMID- 8521596
TI  - Association between creatinine-adjusted and unadjusted urine cotinine values in
      children and the mother's report of exposure to environmental tobacco smoke.
AB  - OBJECTIVE: To examine the association between parents' report of their child's
      secondhand smoke exposure and various adjustments of cotinine concentrations in
      random urine samples. METHODS: Urine cotinine and creatinine were measured in 109
      six to 11-year-old children from predominantly upper middle-class families.
      Cotinine values were considered as: (a) unadjusted, (b) as a cotinine/creatinine
      ratio, (c) as adjusted based on a regression relationship between cotinine and
      creatinine, and (d) and (e) as a cotinine/creatinine ratio adjusted for age and
      sex. RESULTS: Little overlap in cotinine values occurred between exposed and
      nonexposed children, and a dose-response relationship was noted between the
      parental report and the urine cotinine values (r = 0.67). A modest improvement
      occurred in the correlation when the cotinine/creatinine ratio was considered.
      Considering exposure to cigarette smoke outside the home as well as in the
      household only improved the correlation when the former exposure was heavy. A
      high degree of concordance exists between the parents' report of exposure and the
      child's urine cotinine. CONCLUSIONS: The value of adjusting this biochemical
      parameter by various means may be a function of the particular sample being
      investigated, suggesting no one method is universally appropriate.

PMID- 8521597
TI  - Fatty acids and plasma antioxidants in HIV-positive patients: correlation with
      nutritional and immunological status.
AB  - OBJECTIVE: To investigate red blood cell (RBC) and plasma fatty acids (FA) in HIV
      positive patients in relation to oxidative stress and nutritional or
      immunological status. DESIGN AND METHODS: FA, plasma selenium, vitamins A and E
      were measured in 95 patients divided into four groups according to CD4 cells.
      RESULTS: Poly- and di-unsaturated FA (PUFA, DUFA) decreased and saturated FA
      (SFA) increased in RBC in the patients below 400/mm3 and in plasma in the
      patients below 50/mm3. RBC SFA correlated to CD4 cells, PUFA to MDA. Unlike
      vitamin E, plasma vitamin A and selenium decreased in most groups. Plasma SFA and
      MUFA correlated negatively to selenium and PUFA and DUFA to vitamin E. No
      correlation was found between PUFA and nutritional markers. CONCLUSION: FA seem
      to be modified during HIV infection by oxidative stress and disease evolution,
      but not by denutrition.

PMID- 8521598
TI  - Lipoprotein(a): levels in a Swedish population in relation to other lipid
      parameters and in comparison with a male Sri Lankan population.
AB  - OBJECTIVE: To evaluate differences in Lipoprotein (a) [Lp(a)] concentrations
      between a Swedish and Sri Lankan population. METHODS: The distribution of Lp(a)
      and its relation to other lipid parameters, measured with an automated
      turbidimetric method, in 4646 Swedes (1944 females and 2702 males) undergoing
      health screening and 757 randomly selected Sri Lankan males (667 non-CHD and 80
      CHD subjects) was evaluated. RESULTS: The distribution was highly skewed towards
      low values in both the Swedish population and the Sri Lankan male population. The
      Swedish population had a median of 0.16 g/L (reported as total mass) whereas the
      Sri Lankan population median of 0.06 g/L was much lower. For the Swedes, there
      was a small significant difference of 0.03 g/L between the sexes (F < M; p <
      0.001) and Lp(a) was significantly higher in subjects > 50 years of age in both
      sexes (p < 0.002(F); p < 0.02(M)). 29% had Lp(a) values > 0.30 g/L. In the Sri
      Lankan males population Lp(a) was also significantly higher in subjects > 50
      years of age (p < 0.009) but only 7% had an Lp(a) concentration of > 0.30 g/L. In
      the CHD subgroup, though not significant, subjects > 50 years of age had a lower
      Lp(a) concentration, indicating that Lp(a) may be a more significant risk factor
      in younger subjects. Both the Swedish female and male hypercholesterolemic
      subgroups had significantly higher Lp(a) concentrations than normolipemic
      subgroups and the male hypertriglyceridemic subgroups significantly lower Lp(a)
      concentrations than normolipemic. Great differences in Lp(a) levels are thus
      found between the two populations. The differences are similar in normolipemic
      subjects and probably they reflect mainly genetic differences. Lipid/lipoprotein
      concentrations were also found to differ. It is being investigated if this
      reflects differences in CHD prevalence. CONCLUSION: Our data support the
      importance of including Lp(a) measurements when assessing the risk profile for
      premature development of CHD in the individual patient.

PMID- 8521599
TI  - Sialic acid and oxidizability of low density lipoprotein subfractions of
      hyperlipidemic patients.
AB  - OBJECTIVES: Low density lipoprotein (LDL) does not constitute an homogenous
      fraction and it is known that the heavy LDL subfraction is potentially more
      atherogenic than the light one. Because concentration of LDL subfractions tend to
      be different in hyperlipidemias, it was verified whether these subfractions can
      also differ in sialic acid and neutral sugar content, as well as their resistance
      to oxidation. DESIGN AND METHODS: Two subfractions of low density lipoprotein
      (light LDL, density 1.019-1.034 g/mL and heavy LDL, density 1.034-1.063 g/mL)
      were isolated from the plasma of 17 patients with hypercholesterolemia, 11 with
      combined hyperlipidemia, 7 with hypertriglyceridemia, and 19 normolipidemic
      subjects. The content of sialic acids and neutral sugars of apo B was determined,
      respectively, by the periodate-thiobarbituric acid method and by reaction with
      phenol. The oxidation of LDL subfractions was determined by exposure to 5 microM
      copper (II) followed by the measurement of lipid hydroperoxides production by
      high performance liquid chromatography with electrochemical detection. RESULTS:
      The study groups did not differ in the neutral sugar content of LDL subfractions.
      However, compared to normolipidemic subjects, the sialic acid concentration of
      both LDL subfractions was lower in patients with hypercholesterolemia and
      hypertriglyceridemia and higher in those with combined hyperlipidemia (p < 0.05).
      In the hypercholesterolemia and combined hyperlipidemia groups, the lipid
      hydroperoxide content (microM) of heavy LDL was higher than in normolipidemic
      subjects (p < 0.05). CONCLUSIONS: The heavy LDL subfraction was more susceptible
      to oxidation in the patients with combined hyperlipidemia compared to controls
      and the other hyperlipidemic groups. The effect of sialic acids on heavy LDL
      oxidizability seems to vary according to the type of hyperlipidemia.

PMID- 8521600
TI  - Screening for Down syndrome during the first and second trimesters: impact of
      risk estimation parameters.
AB  - OBJECTIVES: To evaluate impact of risk estimation parameters for screening for
      Down Syndrome during the first and second trimesters. METHODS: We prospectively
      examined for their performance in the prenatal prediction of trisomy 21,
      alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic
      gonadotropin (hCG), and its free subunits (free alpha-hCG, free beta-hCG) at both
      the first and second trimesters, and the impact of three sets of published risk
      estimation parameters. A total of 14,612 pregnancies were studied. All Down
      syndrome specimens (12 and 11 cases for first and second trimesters,
      respectively) and a sample of the unaffected pregnancies were analyzed. RESULTS:
      The median multiple of median (MoM) for total hCG was lower in the first
      trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative
      power was observed if the lower variability of the results in the first trimester
      is taken into account (interquartile range of 0.251 vs. 0.338). The choice of
      distribution parameters did not alter significantly the detection rates for the
      various combinations of markers (p > 0.05). False positive rates were affected
      significantly however and for the combination AFP-uE3-free beta-hCG they varied
      from 14.6% to 22.6% (p < 0.001). CONCLUSIONS: Our results suggest that specific
      distribution parameters would be necessary to account for the lower variability
      of the markers in the first trimester and the peculiarity of the total hCG assay
      we used.

PMID- 8521601
TI  - Effect of L-carnitine treatment on very low density lipoprotein kinetics in the
      hyperlipidemic rabbit.
AB  - This study examined the hypolipidemic effect of 4 weeks of L-carnitine treatment
      (170 mg/kg b.w./day) in New Zealand White rabbits fed a high fat diet (5% corn
      oil/0.5% cholesterol). Specifically, [3H] glycerol and [125I] very low density
      lipoprotein (VLDL) turnover studies were conducted to examine the effect of
      treatment on VLDL kinetics. The masses of plasma VLDL-triglycerides (VLDL-TG) and
      VLDL-apoprotein B (VLDL-apoB) were significantly increased by the high-fat diet.
      Four weeks of treatment with L-carnitine significantly reduced these masses.
      Kinetic analysis indicated that fat feeding reduced the fractional catabolic
      rates (FCRs) of VLDL-TG and VLDL-apoB relative to chow-fed controls. The
      transport of these VLDL components was not altered by the diet. L-carnitine
      treatment had no effect on the FCRs of VLDL-TG and VLDL-apoB or on the transport
      of VLDL-apoB. Yet, treatment significantly lowered the transport of VLDL-TG.
      These data indicate that the lipid-lowering effect of L-carnitine in this animal
      model was due, in part, to a decrease in the transport and not due to an
      alteration in the fractional catabolic rate of VLDL-TG.

PMID- 8521602
TI  - Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial
      meningitis.
AB  - We carried out estimations of the following acute phase proteins: C-reactive
      protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha
      2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in
      cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and
      viral meningitis (VM, n = 30). We have shown that determinations of
      concentrations of AAG and CRP in serum and CER in CSF are useful in
      differentiation between BM and VM. The diagnostic power of these three tests (the
      areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is
      bigger, though statistically not significantly, than that of traditional
      parameters of BM in CSF, i.e., total protein concentration and white blood cell
      count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring
      marker in the course of BM treatment. Convenience of serum sampling constitutes
      an advantage over traditional BM parameters in CSF.

PMID- 8521603
TI  - Determination of thalidomide by high performance liquid chromatography:
      methodological strategy for clinical trials.

PMID- 8521604
TI  - Rapid detection of the delta F508 deletion in cystic fibrosis by allele specific
      PCR and electrochemiluminescent detection.

PMID- 8521605
TI  - Nonspecific elevation of troponin T levels in patients with chronic renal
      failure.

PMID- 8521606
TI  - An improved direct method for the measurement of urinary delta-aminolevulinic
      acid.

PMID- 8521607
TI  - Iron as a hepatotoxin.
AB  - Although essential for life, iron in excessive amounts may be toxic. The liver is
      particularly subject to the toxic effects of iron, since it is the major site of
      iron storage. Several inherited and acquired human disorders may result in
      hepatic iron overload, the most common of which are genetic hemochromatosis (GH)
      and transfusional iron overload. GH is an inherited disorder of iron metabolism,
      and in patients with GH excess iron absorbed from the gut is transported through
      the portal vein to the liver. The mechanisms by which excess iron exerts its
      cytotoxic effects include enhanced formation of free radicals and peroxidation of
      organelle membrane lipids. Lipid peroxidation can lead to structural and
      functional alterations in lysosomes, mitochondria and the endoplasmic reticulum.
      With massive iron overload, such iron-induced alterations may cause cell death,
      also known as sideronecrosis. At this stage, fibrogenesis is initiated and, if
      the excess iron is not removed, the increased deposition of collagen progresses
      to cirrhosis. However, the mechanisms underlying iron-induced fibrosis remain
      unclear. Transformation of fat-storing cells to collagen-producing myofibroblasts
      has been proposed to be induced either by iron; by lipid peroxides or other
      cellular factors released from iron-loaded, damaged hepatocytes; or by
      profibrogenic factors produced by activated Kupffer cells. In addition, iron may
      enhance the cytotoxic and, possibly, fibrogenic effects of other liver cell
      damaging agents, such as alcohol or hepatotrophic viruses. Once cirrhosis is
      manifest, patients with GH demonstrate a 200-fold increase in the risk for
      development of hepatocellular carcinoma. In vitro, iron has been shown to possess
      mutagenic properties, but the results from in vivo models in which the genotoxic
      effects of iron overload have been studied are variable. Similarly, although iron
      has mitostimulatory effects on hepatocytes in vivo and preneoplastic cells in
      vitro, its role in tumor promotion and/or progression still remains unclear.
      Cirrhosis itself is of central importance in the carcinogenic process, but
      whether or not iron acts as an additional risk factor in this process, alone or
      by enhancing the tumorigenic properties of other hepatocarcinogens, has yet to be
      established.

PMID- 8521608
TI  - Iron and chronic viral hepatitis: emerging evidence for an important interaction.
AB  - Iron is an essential element for cell survival; it serves as a cofactor for
      essential enzymes in oxidative metabolism and (in the form of heme) as the major
      oxygen transporter in most forms of life on earth. Both deficiency and excess of
      iron often lead to disease. Iron is necessary for the proliferation of
      microorganisms and neoplastic cells. The presence of iron overload facilitates
      infection, as evidenced by the increased risk of persons with hemochromatosis to
      certain infections and by the fact that patients with lesser amounts of hepatic
      iron appear to respond better to interferon therapy for chronic viral hepatitis
      than those with larger amounts of hepatic iron. Viral hepatitis is a common cause
      of morbidity and mortality. Recent studies suggest that there is a key link
      between iron metabolism and the pathophysiology of viral hepatitis. The lobular
      and cellular distribution of iron in the liver may be as important as the total
      quantity of iron present. Whether iron removal will prove useful in the long-term
      management of chronic viral hepatitis is an issue in need of further well
      designed, randomized, controlled trials.

PMID- 8521609
TI  - Update on the use of metabolic probes to quantify liver function: caffeine versus
      lidocaine.
AB  - The search for continues for a safe, accurate and reliable method to quantify
      liver function similar in principle to renal creatinine clearance or pulmonary
      function spirometry tests. When evaluating patients in the more advanced stages
      of chronic liver disease, one's clinical judgement regarding the degree of liver
      dysfunction usually suffices, but in patients with early or only intermediate
      disease, and estimate based on routine blood tests and/or clinical severity
      scores is often unreliable. A more quantitative approach under investigation at
      present has been to monitor specific pharmacokinetic parameters of 'probe' drugs
      metabolized primarily by hepatic cytochrome P-450. These parameters include the
      plasma or salivary clearance rate of the parent compound and/or the formation
      rate of its metabolites. Following a review of basic hepatic pharmacology
      relevant to this topic, we shall explore the advantages and disadvantages of two
      'metabolic probes' that have shown the most promise to date, caffeine and
      lidocaine.

PMID- 8521610
TI  - Nonsteroidal anti-inflammatory drugs: gastroduodenal injury and beyond.
AB  - The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is extensive, and the
      upper gastrointestinal (GI) side effects of these drugs have been well
      recognized. Although much attention has been focused on gastroduodenal ulceration
      and attendant complications, it is becoming more apparent that NSAIDs exert
      potentially important effects on the small bowel and colon. The widespread
      effects of NSAIDs on the GI system, including theories of pathogenesis, will be
      presented here.

PMID- 8521611
TI  - Expression and localization of 92 kDa type IV collagenase/gelatinase B (MMP-9) in
      human gliomas.
AB  - Matrix metalloproteinases play an important regulatory role in tissue
      morphogenesis, cell differentiation and motility, and tumor cell invasiveness. We
      have recently demonstrated elevated activity of the 92 kDa type IV collagenase
      (MMP-9) in human glioblastoma and in the present study examine the relative
      amounts of MMP-9 protein and mRNA in human gliomas and as well as the
      distribution of MMP-9 in human glioma tumors in vivo. Using an enzyme-linked
      immunosorbent assay for the quantitative determination of MMP-9 protein, we found
      that levels were significantly higher in malignant astrocytomas, especially in
      glioblastoma multiforme, than in normal brain tissues and low-grade gliomas. In
      addition, the amount of MMP-9 mRNA, as determined by northern blot analysis was
      higher in anaplastic astrocytomas and glioblastoma multiforme than in normal
      brain tissue and low-grade gliomas. Immunocytochemical staining for MMP-9 showed
      strong cytoplasmic immunoreactivity in the tumor cells and the proliferating
      endothelial cells of glioblastoma multiforme and anaplastic astrocytomas. The
      staining intensity was lowe in low-grade astrocytomas, and was undetectable or
      very low in normal brain astrocytes. The results indicate that expression of MMP
      9 is dramatically upregulated in highly malignant gliomas and correlates with the
      highly malignant progression of human gliomas in vivo, and support a role for the
      MMP-9 in facilitating the invasiveness seen in malignant gliomas in vivo.

PMID- 8521612
TI  - Bone cell matrix promotes the adhesion of human prostatic carcinoma cells via the
      alpha 2 beta 1 integrin.
AB  - Prostatic carcinoma cells have a propensity to metastasize to bone, and we
      propose that this phenomenon may be promoted by the adhesion of metastatic cells
      to bone matrix. Bone matrix is produced by osteoblasts, and we have developed an
      in vitro model of bone matrix by isolating the substratum deposited by human
      osteoblast-like U2OS cells. The collagenous nature of this matrix was
      demonstrated by the incorporation of [3H]proline and its subsequent release by
      purified collagenase. Both U2OS matrix and purified type I collagen stimulated
      the adhesion of human PC-3 prostatic carcinoma cells. Human laminin supported
      adhesion to a much lesser extent, and PC-3 cells did not adhere to fibronectin.
      Adhesion of PC-3 cells to U2OS matrix closely resembled adhesion to purified type
      I collagen with respect to (a) inhibition by a collagen-derived peptide and by
      antibodies raised against alpha 2 or beta 1 integrin collagen receptor subunits;
      (b) lack of inhibition by RGD (Arg-Gly-Asp) peptides; (c) stimulation by Mn2+ and
      Mg2+ ions but not by Ca2+ ion; and (d) stimulation by the phorbol ester PMA
      (phorbol 12-myristate 13-acetate). This adhesion was also stimulated (2.3-fold)
      by transforming growth factor beta (TGF-beta), which is a major bone-derived
      growth factor. We conclude that human osteoblast-like matrix is an adhesive
      substrate for PC-3 prostate carcinoma cells. This adhesion appears to be mediated
      by the interaction of alpha 2 beta 1 integrin on PC-3 cells with matrix-derived
      collagen. The stimulation of this adhesion by TGF-beta suggests that the co
      expression of TGF-beta and type I collagen in bone may synergistically facilitate
      the adhesion of metastatic cells to bone matrix proteins and thereby increase
      their localization in the skeleton.

PMID- 8521613
TI  - Expression and immunohistochemical localization of cathepsin L during the
      progression of human gliomas.
AB  - Recent studies suggest that cysteine proteinase cathepsin L is involved in the
      process of tumor invasion and metastasis. We examined cathepsin L activity in
      brain tumor tissue samples by an enzymatic assay, and cathepsin L protein content
      by enzyme-linked immunoadsorbent assays and Western blotting to determine whether
      increased levels of cathepsin L correlate with the progression of human gliomas.
      Native and acid-activatable cathepsin L activities were highest in glioblastomas
      followed by anaplastic astrocytomas and were lowest in low-grade gliomas and
      normal brain tissues. Significantly higher amounts of an M(r) 29,000 cathepsin L
      were present in glioblastomas and anaplastic astrocytomas than in normal brain
      tissues and low-grade glioma tissue extracts. Using specific antibodies to
      cathepsin L, we also studied its cellular distribution by immunohistochemical
      procedures. Higher diffuse cathepsin L immunoreactivity was found in
      glioblastomas than in low-grade gliomas and normal brain tissue samples. Finally,
      the addition of cathepsin L antibody inhibits the invasion of glioblastoma cell
      lines through Matrigel invasion assay. These results suggest the expression of
      cathepsin L is dramatically upregulated in malignant gliomas and correlates with
      the malignant progression of human gliomas in vivo.

PMID- 8521614
TI  - Metastatic colorectal cancer cells induce matrix metalloproteinase release by
      human monocytes.
AB  - Matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) facilitate tumor invasion and
      metastasis via basement membrane degradation. In colorectal cancer (CRC)
      specimens, MMP production is largely stromal in origin, implicating monocytes (M
      phi s) and fibroblasts. We hypothesize that CRC cells induce stromal cell MMP
      production. This study examines the differential effect of metastatic and non
      metastatic CRC cells on M phi MMP production. The human M phi line THP-1 was co
      cultured with either a non-metastatic human CRC cell line (SW620-P) or a
      metastatic clone (SW620-S5) established by serial cecal transplantation of SW620
      P in nude mice. Conditioned medium MMP activity and cellular MMP mRNA expression
      were assessed by gelatinase zymography and Northern blot analysis, respectively.
      Neither CRC line released MMP-2 or MMP-9. Isolated THP-1 M phi s produced basal
      levels of both MMP-2 and MMP-9. The level of MMP-9 activity was increased
      moderately by co-culture of M phi s with the metastatic SW620-S5 clone, but
      decreased by the non-metastatic SW620-P cells. MMP-2 activity was greatly
      augmented by co-culturing M phi s with SW620-S5 cells, but was not affected by
      SW620-P cells. The stimulatory effect of SW620-S5 cells on MMP-2 secretion was
      confirmed by Western blot analysis. Both isolated and co-cultured M phi s
      expressed MMP-2 mRNA while SW620-S5 cells under similar conditions did not,
      implicating M phi s as the source of increased MMP-2 activity. Since the
      induction of MMP-2 activity was not associated with a parallel increase in M phi
      MMP-2 mRNA, the modulation of M phi MMP-2 release appears to be post
      transcriptionally regulated. Metastatic CRC cells are distinct from non
      metastatic cells in their ability to induce M phi MMP release. This observation
      emphasizes the role of M phi-derived MMPs in facilitating CRC invasion and
      metastasis and suggests modulation of stromal cell MMP production by CRC cells in
      a paracrine fashion.

PMID- 8521615
TI  - Expression and localization of 72 kDa type IV collagenase (MMP-2) in human
      malignant gliomas in vivo.
AB  - The 72 kDa type IV collagenase (gelatinase), a matrix metalloproteinase (MMP-2),
      has been proposed to potentiate the invasion and metastasis of malignant tumors.
      To determine the potential role of the MMP-2 in human gliomas and normal brain
      tissue, we examined the relative amounts of protein, mRNA, and distribution.
      Using gelatin zymography, densitometry, and an enzyme-linked immunosorbent assay
      for the quantitative determination of the MMP-2, we found that the enzyme's
      activity was significantly elevated in malignant astrocytomas, especially in
      glioblastoma multiforme, compared to low-grade glioma and normal brain tissues.
      As determined by Northern blot analysis, the amount of MMP-2 mRNA transcript was
      higher in anaplastic astrocytomas and glioblastoma multiforme tumors than in
      normal brain tissues or low-grade gliomas, a finding that was consistent with the
      amounts of MMP-2 protein detected in these tissues. Immunohistochemical studies
      demonstrated that MMP-2 was localized in tumor cells and vasculature cells of
      malignant astrocytomas. Staining intensity was clearly lower in low-grade
      astrocytomas, and immunoreactivity was very low or undetectable in normal brain
      astrocytes. The results suggest that expression of the MMP-2 is dramatically
      upregulated in malignant gliomas, correlating with the malignant progression of
      human gliomas in vivo.

PMID- 8521616
TI  - Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice.
AB  - We established a peritoneal-metastatic model for scirrhous gastric carcinoma.
      Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM
      2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic
      nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which
      developed no peritoneal metastasis after intraperitoneal inoculation. The
      histologic findings of orthotopic-implanted tumor in the stomach show scirrhous
      type while those of subcutaneous-implanted tumor show medullary type. There might
      be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis.
      We next investigated the differences in the biological behavior of the original
      OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the
      two cell lines were similar to each other. The specific chromosomes, add(6)(q13),
      del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM
      2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam
      and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E
      cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells.
      Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of
      OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher
      than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody.
      The invasion activity of OCUM-2MD3 cells was increased in the presence of
      peritoneal fibroblast. In this study, it was suggested that orthotopic
      implantation of cancer cells might have an effect on the acquisition of
      metastatic ability. beta 1-integrin and peritoneal fibroblasts might be
      correlated with peritoneal metastasis. This peritoneal-metastatic model should be
      useful for analysing the mechanism of peritoneal metastasis of human scirrhous
      gastric cancer.

PMID- 8521617
TI  - Porcine splenic peptides (Polyerga) decrease the number of experimental lung
      metastases in mice.
AB  - Preparations of splenic peptides under the name of Polyerga are being tested in
      numerous experimental immunomodulating and antitumorous models and are also used
      during supportive treatment of tumorous patients. Further, the incidence of
      experimental lung metastases of melanoma cells in mice was significantly reduced
      if we used Polyerga preparations. The aim of our investigation was to determine
      whether Polyerga is active directly against tumor cells or whether its activity
      is manifested by modulating immune and other possible abilities of the organism.
      To clarify the problem glycopeptides containing Polyerga were incubated with
      melanoma B16F10 cells in vitro and the plating efficiency of these cells
      determined when cultivated in medium, or in medium with different doses of the
      same Polyerga preparation. The cells preincubated in medium only reacted to the
      addition of increasing doses of Polyerga, 150 pg or more, by raising colonies
      number. However, 24-h incubation of melanoma cells in the presence of 150
      micrograms of Polyerga per ml significantly reduced the number of tumor cell
      colonies in comparison to the corresponding cell cultures previously not exposed
      to Polyerga. These in vitro studies were extended to in vivo application using
      C57B1/GoZgr mice injected i.v. with melanoma cells pretreated with Polyerga in
      vitro or previously not treated. A group of the treated mice was further injected
      i.p. with Polyerga. All the mice were killed at a particular time and the number
      of lung nodules determined. A significant difference to the control values was
      noticed in each group that used Polyerga, regardless of the exposure of melanoma
      cells to Polyerga in vitro, in vivo or to combined treatment. The efficiency of
      Polyerga application 7 days following i.v. injection of control melanoma cells
      (cultivated in medium only) when the nodules already exist, was further evaluated
      in a combined treatment using DTIC, a drug of choice in melanomas. The smallest
      incidence of experimental lung metastases was observed in the group exposed to
      the combination of DTIC and Polyerga. Polyerga preparation is thus active against
      melanoma cells, particularly in vivo and if combined with chemotherapy.

PMID- 8521618
TI  - EGF stimulates lamellipod extension in metastatic mammary adenocarcinoma cells by
      an actin-dependent mechanism.
AB  - Changes in lamellipod extension and chemotaxis in response to EGF were analysed
      for MTLn3 cells (a metastatic cell line derived from the 13762NF rat mammary
      adenocarcinoma). Addition of EGF produced a cessation of ruffling followed by
      extension of hyaline lamellipods containing increased amounts of F-actin at the
      growing edge. A non-metastatic cell line (MTC) derived from the same tumor did
      not show such responses. Lamellipod extension was maximal within 5 min, followed
      by retraction and resumption of ruffling. Maximal area increases due to
      lamellipod extension occurred at about 5 nM EGF. Chemotactic and chemokinetic
      responses, measured using a microchemotaxis chamber, were also greatest at 5 nM.
      Cytochalasin D inhibited EGF-stimulated responses including lamellipod extension,
      increases in F-actin in lamellipods, and chemotaxis. Nocodazole affected
      chemotaxis at higher concentrations but not EGF-induced lamellipod extension. We
      conclude that polymerization of F-actin at the leading edges of lamellipods is
      necessary for extension of lamellipods and chemotaxis of MTLn3 cells in response
      to EGF. The motility and chemotaxis responses of this metastatic cell line have
      strong similarities to those seen in well-characterized chemotactic cells such as
      Dictyostelium and neutrophils.

PMID- 8521619
TI  - Oncogene-dependent expression of CD44 in Balb/c 3T3 derivatives: correlation with
      metastatic competence.
AB  - Oncogene-dependent regulation and tumor relatedness of CD44 expression were
      investigated in Balb/c 3T3 cells and their derivatives transformed with different
      ras oncogenes (metastatic tumor model) or the human c-sis oncogene (non
      metastatic model). Ras transformants using either the Harvey or Kirsten oncogenes
      expressed high levels of cell surface CD44 protein that bound fluoresceinated
      hyaluronan (HA). Much lower levels of CD44 were expressed in parental 3T3 cells,
      ras- revertants generated from Kirsten-transformed cells, or c-sis transformants,
      confirming the significance of the ras oncogene in this upregulation. To
      determine whether endogenous HA regulates these parameters, hyaluronidase
      treatment of ras transformants exposed more cell surface CD44 to anti-CD44
      antibody and increased fluoresceinated HA binding; this did not occur with 3T3 or
      c-sis transformants. CD44 expression and its HA-binding function were conserved
      in a panel of in vivo primary and lung metastatic tumor cell lines derived from
      ras transformants. Ras transformants also retained the ability to downregulate
      CD44 protein levels in confluent cultures which occurred through a translational
      or post-translational mechanism (as CD44 mRNA levels were not reduced). These
      results taken together demonstrate that ras-dependent regulation of CD44 may
      correlate with tumor progression and metastasis in vivo, possibly (although not
      exclusively) supporting CD44's importance in metastatic progression.

PMID- 8521620
TI  - Opportunistic infections of the central nervous system in children with HIV
      infection: report of 9 autopsy cases and review of literature.
AB  - Central nervous system (CNS) abnormalities attributed to direct effects of HIV
      infection are seen in most of children with acquired immunodeficiency syndrome
      (AIDS). Secondary CNS infections with opportunistic and common pathogens are
      infrequent in this age group. We report 9 cases of opportunistic infection of the
      CNS found among 65 autopsy cases of pediatric AIDS. These included 4 cases of
      cytomegalovirus (CMV) infection, 1 of which was associated with aspergillosis,
      and 2 cases of candidiasis, 1 of which coexisted with Mycobacterium avium
      intracellulare (MAI) infection. There were also 2 cases of leptomeningitis, 1 due
      to Mycobacterium tuberculosis (MTB) and the other to Cryptococcus neoformans. In
      1 child progressive multifocal leukoencephalopathy (PML) coexisted with mycotic
      encephalitis caused by an Aspergillus sp.

PMID- 8521621
TI  - Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a
      patient with acute amyotrophic lateral sclerosis and presenile dementia.
AB  - This is the report of a case of a 41-year-old male patient with a rapidly
      progressing amyotrophic lateral sclerosis (ALS) combined with a severe presenile
      dementia. Screening for antibody binding on fresh-frozen human brain sections, we
      found that the patient's cerebrospinal fluid contained antibodies against
      microglia, the dominant and potentially cytotoxic immuneffector cell of the
      brain. This finding extends previous observations of CSF autoantibodies against
      microglia in neurodegenerative diseases. It demonstrates that in addition to
      antigens of neuronal origin (e.g. anti-Purkinje cell antibodies in paraneoplastic
      cerebellar dysfunction), glial antigens also appear to be under the surveillance
      of the CNS and/or the peripheral immune system. Our data provide evidence for a
      close link between neurodegeneration and the activation of microglia; a possible
      local antigen production against microglia/brain macrophages, which might
      regulate the concomitant glial activation in neurodegenerative diseases; and the
      presence of microglia-binding cerebrospinal antibodies as a marker for the acuity
      of the disease process underlying the acute deterioration of the neurological and
      cognitive performance in patients with, e.g., ALS. Future therapeutic strategies
      could therefore include the modulation of the possibly disease-promoting
      activation of microglia/brain macrophages.

PMID- 8521622
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL)--confirmation by cerebral biopsy in 2 cases.
AB  - CADASIL is a recently recognized familial form of subcortical multi-infarct
      dementia. The pathogenesis of the disease is unknown, but it is characterized
      pathologically by a novel vasculopathy affecting leptomeningeal and subcortical
      arteries. We describe 2 cases in which the diagnosis could be made from the
      cerebral biopsy appearances of affected leptomeningeal vessels. The
      ultrastructural appearances of the vessel wall deposit are illustrated, and their
      similarity to those of immune complex deposits discussed.

PMID- 8521623
TI  - Massive appearance of corpora amylacea in postnatal anoxic encephalopathy.
AB  - Massive appearance of corpora amylacea (CA) was reported in a 23-year-old male
      who had suffered from anoxic encephalopathy due to anesthetic accident in
      babyhood. The distribution of CA was unique compared with that of usual CA. In
      addition, the stainability with hematoxylin-eosin showed a distinct difference
      from subpial CA, though the ultrastructure was identical. The present study is to
      demonstrate a case with massive appearance of CA and to discuss this variety of
      CA, which could contribute to further studies of polyglucosan bodies.

PMID- 8521624
TI  - A congenital syndrome of mental deficiency, gait disturbance, sensorineural
      deafness and pigmentary retinopathy associated with premature atherosclerosis.
AB  - Many neurological disorders have been described in combination with sensorineural
      hearing loss and pigmentary retinopathy. We present the clinicopathological case
      of such a combination, associated with premature atherosclerosis of large
      cerebral arteries. In the literature dealing with the combination of deafness and
      pigmentary retinopathy, none of the many described syndromes was associated with
      premature atherosclerosis. The mitochondrial myopathy, encephalopathy, lactic
      acidosis, early atherosclerosis and stroke-like episodes (MELAS) syndrome can
      include deafness and blindness. In this syndrome small cerebral arteries are
      affected. In our case we did not find electron microscopic evidence of
      mitochondrial myopathy. Also the syndrome with encephalopathy, deafness,
      blindness and ataxia in young women is attributed to microangiopathy with small
      brain infarcts and retinal infarcts. In contrast, in our case, large cerebral
      arteries are affected. In the reverse order, none of the conditions with early
      atherosclerosis has been reported in combination with sensorineural deafness and
      pigmentary retinopathy. There is some similarity of our case to cases of Usher
      syndrome, type II. In the Usher syndrome, plasma lipid disturbances have been
      described and neuroradiological evidence of decreased circulation in the
      posterior cerebral circulation has been published. We suggest that in cases of
      congenital or acquired oto-ophthalmo-neurological disease the cerebral
      circulation and the lipid metabolism should be analyzed.

PMID- 8521625
TI  - Methylmalonic acidemia: brain lesions in a case of vitamin B12 non-responsive
      (mut0) type.
AB  - Neuropathological findings were described in a 9-day-old female infant who died
      of the vitamin B12 non-responsive (mut0) type of methylmalonic acidemia (MMA).
      Widespread karyorhectic fragments of varying size and shape were noted throughout
      the brain, in particular densely accumulated in the cerebellar granular layers
      and the layer IV of the striate cortex. Bilateral or symmetrical necrotic foci
      were observed in various regions of the grey matter: Sommer's sector of the
      hippocampus, basal ganglia, thalamus, hypothalamus and brainstem. In the cerebral
      cortex small spongy necrotic foci were scattered mainly in the depths of gyri.
      Alzheimer type II astrocytes appeared in the preserved zone of the caudate
      nucleus. Myelinated nerve fibers in the brainstem were spongy or vacuolated,
      whereas peripheral myelin sheaths of cranial nerves were intact. Multiple
      hemorrhagic foci were noted in the cerebellum, predominantly the granular layers.
      The lymphoid tissue in the spleen and the thymus was hypoplastic. It may be
      difficult to explain exactly the mechanisms of the pathological changes observed
      here on routine light microscopy; the outcome of systemic ischemia/hypoxia before
      death cannot be completely ignored. But, it is suggested that widespread
      karyorhexis may occur selectively in specific cells (or cell groups), including
      immature neurons and other cellular components (glial and/or mesenchymal cells)
      among the patients with the mut0 type of MMA.

PMID- 8521626
TI  - Leptomeningeal dissemination of malignant glioma: immunohistochemical analysis of
      tenascin and glial fibrillary acidic protein.
AB  - Immunohistochemical expression of tenascin (TN) and glial fibrillary acidic
      protein (GFAP) was investigated in 9 human malignant gliomas with leptomeningeal
      dissemination. In these patients intracerebral glioma tissues obtained at
      operation and/or autopsy displayed localized expression of TN in tumor vessels
      and stroma. In contrast, TN was expressed in the tumor vessels, tumor stroma, and
      the cytoplasm of tumor cells to a high degree throughout all the leptomeningeal
      tumor tissues obtained at autopsy, whereas there was much less expression of GFAP
      in these tissues than at the primary site. These findings suggest that TN
      expression and decrease of GFAP expression in glioma tissue may be involved in
      the development of leptomeningeal dissemination.

PMID- 8521627
TI  - Cerebral magnetic resonance imaging pathology and cerebro-spinal fluid protein in
      sporadic amyotrophic lateral sclerosis (sALS).
AB  - In 3 out of 20 patients with sporadic amyotrophic lateral sclerosis (sALS),
      cranial magnetic resonance imaging detected multiple demyelinating lesions. All 3
      patients died from definite upper and lower motor neuron degeneration. In all 3
      cases total cerebro-spinal fluid (CSF) protein remained within normal ranges, and
      a blood-CSF barrier dysfunction was not detectable. In one of the patients
      multifocal CNS demyelination coincided with an intrathecal synthesis of
      immunoglobulin-G and autochthonous CSF oligoclonal IgG banding (OCB) early in
      disease. Neither absolute or age-corrected survival nor disease progression
      differed for patients with and without cerebral MR lesions, or normal vs.
      elevated CSF total protein. Evaluating the CSF in an extended patient sample (n =
      29), we found the total CSF protein elevated in 5 of 16 men and none of 13 women
      (p < 0.05). The mean age-corrected CSF protein content [practical reference limit
      = (age x 3.3) + 300 mg/l] was higher in male (465 mg/l +/- 32 SE) than in female
      (350 mg/l +/- 26 SE) sALS patients (p < 0.01). This coincides with a male
      preponderance in sALS.

PMID- 8521628
TI  - Combined malformation of the Vein of Galen and of spinal vessels: endovascular
      embolization.
AB  - This case report describes a combination of arterio-venous malformation of the
      Vein of Galen (VGAM) and intraspinal venous malformation in a newborn. Successful
      local embolization by Tantal coils was followed by spinal paraplegia. The child
      died at the 26th postnatal day. The neuropathological aspects of this course will
      be discussed including a review of the literature.

PMID- 8521629
TI  - Spinal epidural malignant lymphoma presenting with spinal cord compression.
AB  - Malignant lymphoma initially presenting with symptoms and signs of spinal cord
      compression are a rare occurrence. We present 20 cases of spinal epidural
      lymphoma first diagnosed on laminectomy biopsy specimens with a review of
      clinical data and histology, as well as an immunohistochemical study to determine
      the immunophenotype of these lymphomas. Eighteen cases were typed as B cell
      lymphomas, 2 as T cell lymphomas.

PMID- 8521630
TI  - Motor neuron disease with involvement of the pallido-luysio-nigral system and
      mesencephalic tegmentum.
AB  - A rare case of motor neuron disease and involvement of the pallido-luysio-nigral
      system and brainstem tegmentum is presented. A 51-year-old man developed
      progressive muscle atrophy with fasciculation predominantly in the shoulder
      girdle, upper arms, upper back, and neck in addition to hyperreflexia and a
      positive Chaddock reflex. He also had retinitis pigmentosa, high arched palate,
      and mild hand tremor. He eventually developed bulbar palsy and died of paralysis
      of the respiratory muscles 11 years after the onset of his illness.
      Neuropathological examinations showed prominent neuronal loss and gliosis in the
      pallido-luysio-nigral system and the tegmentum of the brainstem in addition to
      the simultaneous involvement of the upper and lower motor neurons. This patient
      and 6 similar patients are discussed in relation to pallido-luysio-nigral atrophy
      and the topographic distribution of degeneration in amyotrophic lateral
      sclerosis.

PMID- 8521631
TI  - Intracranial primary leiomyosarcoma arising in a teratoma of the pineal area.
AB  - The case of a 33-year-old man with a primary leiomyosarcoma arising in a mature
      teratoma in the pineal area is presented. The tumor extended into the posterior
      part of the third ventricle and caused hydrocephalus. Its smooth muscle
      derivation was confirmed by immunohistochemistry and electron microscopy. The
      patient has been followed for more than 2 years after surgery and postoperative
      radiotherapy. He has full working capacity and there are no signs of tumor
      recurrence. To our knowledge this is the first presentation of a leiomyosarcoma
      derived from a teratoma in the pineal area.

PMID- 8521632
TI  - [Two siblings of familial amyotrophic lateral sclerosis with multisystemic
      degeneration characterized by mild involvement of the middle root zone of the
      posterior column, Clarke's nuclei and spinocerebellar tract].
AB  - The aim of this study is to clarify the clinicopathological characteristics of
      the multisystem degeneration seen in two male siblings with familial amyotrophic
      lateral sclerosis (FALS). A similar neurological disorder affected their elder
      sister and paternal uncle, but not their parents. The older brother (case 1)
      developed muscular weakness at 50 years of age and the younger brother (case 2),
      at 42 years of age. The duration of illness was 19 months in case 1 and 31 months
      in case 2. The clinical picture was the common (suspended) form in case 1 and the
      pseudopolyneuritic form in case 2. Pyramidal tract sign was obscure in both cases
      and cerebellar sign, sensory disturbance, sphincter disturbance and oculomotor
      palsy were not observed in either case. Neuropathological examination revealed
      similar findings in the two cases: 1) marked loss of lower motor neurons in the
      spinal anterior horn and motor nuclei of the lower brain stem in both cases, with
      neuronal loss of Onuf's nuclei in case 2; 2) very mild involvement in Clarke's
      nuclei, the dorsal and ventral spinocerebellar tracts and the middle root zone of
      the posterior column; 3) relatively well preserved Betz cells in the upper motor
      cortex with the appearance of a few macrophages, and mild changes in the
      pyramidal tract of the spinal cord; and 4) mild degenerative changes in the
      pallidoluysian system and the dentatorubral system. The most characteristic
      pathological findings common to both cases were the extremely mild involvement of
      the middle root zone of the posterior column, Clarke's nuclei and spinocerebellar
      tracts. The pattern of lower motor neuron system degeneration paralleled the
      development of clinical features. Genetic studies demonstrated no mutations in
      exons 1, 2 and 4 of Cu/Zn-binding superoxide dismutase gene. We emphasized the
      existence of mild involvement of middle root zone of posterior column, Clarke's
      nuclei and spinocerebellar tract in FALS with multisystemic degeneration.

PMID- 8521633
TI  - [Intracellular signal transduction of endocrine organs and expanded DNA fragment
      size in myotonic dystrophy].
AB  - The Ellsworth-Howard (EH) test was performed in 16 patients with myotonic
      dystrophy (DM), who were divided into two groups according to serum calcium
      level; Group I showing normal serum calcium (8 patients) and Group II with
      hypocalcemia (8 patients). Patients in Group II were recognized as having
      pseudohypoparathyroidism (PHP) type II and those in Group I as normal. Therefore,
      it was suggested that an abnormality of A kinase might be present in Group II
      patients. We additionally performed the thyrotropin releasing hormone (TRH)
      tolerance test in the same patients and 7 normal controls to examine an
      abnormality of C kinase. delta TSH (delta TSH: peak minus pre TSH) values in DM
      patients were significantly lower than those in normal controls. Moreover, delta
      TSH values in Group II were significantly lower than those in Group I. It was
      suggested that the abnormality of C kinase might be present in Group II patients.
      Taken together, our results indicated that some patients with DM might possess
      abnormalities of signal transduction of both A and C kinases. We compared the
      degree of endocrine involvement determined by both the EH test and the TRH
      tolerance test with expanded DNA fragment (EF) size determined by standard
      Southern blot analysis using an appropriate cDNA probe (cDNA25 probe). There was
      significant negative correlation between EF size and the results of the EH test
      and negative correlation between the EF size and the results of the TRH tolerance
      test. These findings suggested that EF size might be correlated with disease
      severity in affected endocrine organs.

PMID- 8521634
TI  - [Changes in neuropsychological functions following cardiovascular surgery].
AB  - This study was designed to elucidate if there is a potential hazard of developing
      neuropsychological deterioration after major cardiovascular surgery.
      Neuropsychological functions were studied in 49 patients before and after cardiac
      (coronary artery bypass, cardiac valve replacement, etc.) and thoracic aortic
      surgery (aortic aneurysm). Neuropsychological examinations using 5 batteries
      (Mini-Mental State Examination, Cross Cultural Cognitive Examination, Miyake's
      Verbal Memory Test, Benton Visual Retention Test and Wisconsin Card Sorting Test)
      were performed before surgery and subsequently at 3 weeks and 8 months after.
      Twenty-five of 49 patients (51%) showed a significant deterioration at least in
      one of the test batteries. There was no significant relation between age or
      educational levels and post-surgical impairment of cognitive function. The
      impairment of cognitive function was found mainly in the "memory function".
      Follow up examinations were carried out on 31 of the 49 patients 8 months after
      surgery. Among these patients, 13 patients did not show any changes in cognitive
      function throughout the study period. Eleven of the 16 patients who developed a
      decrease in cognitive function for a certain period after surgery (3 weeks),
      recovered to the same level at the follow-up examination that it was prior to the
      surgery. Cognitive function in five patients did not improve and remained at the
      decreased level. The other two patients whose function was normal at the first
      post-surgical examination, were found to have developed impairment of cognitive
      function at the follow up. Although the patients had some deficits on their
      neuropsychological function, they scarcely complained about any problems in their
      daily life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521635
TI  - [Pulse-dose cyclophosphamide therapy for steroid-refractory autoimmune
      neurological diseases].
AB  - Eight patients with neuroimmunological disorders refractory to conventional
      immunotherapies were given totally 17 courses of pulse-dose cyclophosphamide. The
      regimen consisted of 600 mg/m2 of intravenous cyclophosphamide at days 1,2,4,6
      and 8 and infusion of 2,500-3,000 ml of fluids in order to avoid hemorrhagic
      cystitis. Some cases were followed by a monthly intravenous dose of
      cyclophosphamide as a booster treatment. As a result, all but one case of neuro
      Behcet disease have shown neurological improvements. In particular, a complete
      remission was obtained in two cases of vasculitic neuropathy and a case of
      chronic inflammatory demyelinating polyneuropathy. The side effects, notably,
      granulocytopenia, alopecia, hemorrhagic cystitis and anorexia, are major
      problems. Granulocytopenia started 10 days after the first dose and the number of
      leucocytes was the lowest at day 15. However, the number steadily recovered
      thereafter without the use of granulocyte colony stimulating factor. There was no
      serious infections during the course. For neuroimmunological disorders, the pulse
      dose cyclophosphamide therapy would serve a useful alternative when the
      conventional therapies are not efficacious or difficult to continue because of
      the adverse side effects.

PMID- 8521636
TI  - [Fall in the elderly and periventricular hyperintensity].
AB  - To investigate the relationship between brain white-matter changes and incidences
      of falling in the elderly, we studied periventricular hyperintensity (PVH) on
      brain MRI and history of falling in 73 neurologically normal elderly people. They
      were divided into 3 groups: group I; 9 prone to falling (mean ages 79 years),
      group II; 16 who felt mild gait disturbance without falling (75), group III; 48
      asymptomatic controls (76). We evaluated white-matter changes as the sum of the
      length of PVH at 4 and 8 measuring points. Cognitive function and body sway were
      also evaluated. The frontal PVH was significantly larger in the group I than in
      the other two groups. Group I showed significantly lower Kohs' IQ than those in
      the other two groups. There was no difference in body sway among the groups.
      These results suggests that the propensity to falling in the elderly may be an
      initial symptom of frontal white-matter changes.

PMID- 8521637
TI  - [A study of infarction in the region of the anterior inferior cerebellar artery].
AB  - Sixteen patients with infarction in the region supplied by the anterior inferior
      cerebellar artery (AICA) were studied to assess the mechanism and its clinical
      features. Risk factors involved hypertension, diabetes mellitus, a history of
      cerebrovascular disease and hyperlipidemia in seven patients (44%), while smoking
      was found in six (38%). The pathogenesis of these patients was thought to be
      thrombotic in all 16 patients, and lesions of the vertebrobasilar system were
      noted in 7 out of 13 patients (54%) who underwent cerebral angiography. Gasperini
      syndrome (AICA syndrome+abducens paralysis) occurred in two patients (13%), and
      five patients (31%) showed only cerebellar ataxia (3 had infarction confined to
      the middle cerebellar penduncle and 2 had infarction confined to the cerebellar
      hemisphere). As a result of analysis of clinical symptoms in nine patients with
      the incomplete AICA syndrome, loss of hearing in six patients (67%) and
      cerebellar ataxia in all nine patients were noted. We postulated that large
      artery occlusive disease or branch atheromatous disease resulted in an infarction
      in the region of the AICA. It is necessary to consider infarction of the AICA
      region in patients who present a unilateral hearing loss and cerebellar ataxia.

PMID- 8521638
TI  - [Guillain-Barre syndrome associated with external ophthalmoplegia, consciousness
      disturbance, and extensor plantar responses: an overlap between Guillain-Barre
      syndrome and Bickerstaff's brainstem encephalitis].
AB  - A 14-year-old girl developed diplopia and ataxic gait following upper respiratory
      tract infection. On day 3, she became lethergic, but was easily roused on
      stimulation. Neurologic examinations showed external ophthalmoplegia,
      tetraplegia, tendon areflexia, and extensor plantar responses. CSF protein was 93
      mg/dl with normal cellurality on day 25. Serum in the acute phase of her illness
      had autoantibodies to gangliosides GQ1b and Ga1NAc-GD1a. An EEG showed bilateral
      theta activity. Results of ABR, SEP and blink reflexes suggested the presence of
      intramedullary brainstem lesion. She received plasmapheresis on days 4, 5 and 6.
      Neurological signs immediately improved. Five months after onset of neurological
      symptoms, she had no neurological abnormalities except for tendon areflexia.
      Electrophysiologic studies returned to normal concurrently with her clinical
      improvement. This patient demonstrates an overlap between Guillain-Barre syndrome
      and Bickerstaff's brainstem encephalitis.

PMID- 8521639
TI  - [A case of subacute sensory neuropathy associated with extraovarian serous
      papillary adenocarcinoma of the peritoneum].
AB  - We reported a case of subacute sensory neuropathy. A 78-year-old woman was
      admitted to Kenwakai Hospital because of progressive numbness in her hands and
      feet. Four months before admission, numbness and tingling sensations appeared in
      her hands and feet, and subsequently she felt difficulty in skilled finger
      movement. On general examination, she was found to have a mass in the right lower
      abdomen. Neurological examination revealed marked loss of position sense and
      vibratory sense in the distal extremities, and mild reduction of sensation to
      pinprick and light touch in the distal extremities. Stretch reflexs were
      depressed in the upper limbs and absent in the lower limbs. Her gait was unsteady
      and Romberg's sign was positive. She showed no cranial nerve dysfunction,
      cerebellar ataxia, muscle weakness, and autonomic dysfunction. Blood examination
      revealed high TTT (11.3Kunkel U), high ZTT (16.4Kunkel U) titer. Tumor markers
      were normal except for CA125 (93 U/ml). The cerebrospinal fluid showed 48 mg/dl
      of protein, 10.6 mg/dl of IgG. and an almost normal cell count (5.3/mm3). Serum
      was tested by immunohistochemical staining. Only the cytoplasm of neurons in the
      dentate nucleus and brain stem was stained on a rat's brain. Sural nerve biopsy
      showed a severe loss of large myelinated fibers. An exploratory laparotomy
      revealed a peritoneal tumor, 5 cm in diameter, and it was removed. During the
      surgery, other than a few rice-sized nodules in the cul-de-sac, there was no
      evidence of tumor in bilateral ovaries. The tumor was proven to be a serous
      papillary adenocarcinoma with psammoma bodies resembling ovarian cancer.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8521640
TI  - [Idiopathic acquired generalized anhidrosis with normal numbers of eccrine gland
      nerve terminals and unmyelinated axons. A case report].
AB  - A 37-year-old man with acquired generalized anhidrosis but without other
      autonomic or somatic abnormalities (idiopathic acquired generalized anhidrosis)
      is described with special reference to histologic and morphometric findings of
      the eccrine gland and its nerve terminals and unmyelinated axons. The patient was
      admitted to our hospital in August 1989 with complaints of heat intolerance and
      anhidrosis of the face, trunk, and both limbs. General physical and neurological
      examinations revealed no abnormalities except generalized anhidrosis. Sweating
      tests revealed anhidrosis of most surfaces of the body except the axillae,
      mammary areolae, forearms, hands, popliteal fossae, and plantar surfaces.
      Sympathetic skin responses were absent in the axillae, and were decreased on the
      palms. Iontophoretically applied pilocarpine revealed a complete absence of
      active eccrine glands on the dorsal surface of the right foot. No other
      abnormalities were revealed by autonomic function tests. Light and electron
      microscopic studies of the eccrine glands of the distal and lateral aspects of
      the left leg were performed in this patient and six control subjects.
      Infiltration of mononuclear inflammatory cells around the duct and secretory coil
      of a limited number of eccrine glands on multiple sections was found only in this
      patient. Electron microscopic morphometric evaluation of the eccrine glands,
      associated nerve terminals and unmyelinated axons of this patient revealed no
      definite alterations when compared with those of the six control subjects.
      Therefore, we concluded that the nerves innervating the eccrine glands were not
      affected in this patient and suspect that either the cholinergic receptors or the
      function of secretory cells of the eccrine glands were involved.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8521641
TI  - [A case report of pyomyositis--early diagnosis and follow-up by MRI].
AB  - We report a rare case of pyomyositis in a 28-year-old Japanese woman who was not
      immunocompromised. She was admitted because of high fever, sore throat, and
      severe tenderness and swelling of the right calf. Redness, swelling, and
      tenderness indicated presence of acute inflammation in the calf. CT of the lower
      extremities demonstrated low density areas in the right soleus muscle and
      surrounding fascia with marked swelling, which were of high signal on T2 weighted
      images of MRI. There was no finding of abscess formation. A tentative clinical
      diagnosis of acute pyomyositis was made, and antibiotics therapy with a
      combination of fosfomycin and sulbactam/cefoperazone was started although the
      arterial blood culture was negative for bacteria. Associated acute tonsilitis was
      the most probable focus of pyomyositis. Antibiotics relieved her symptoms, and
      the inflammation subsided in several weeks. No surgical procedure was necessary.
      MRI taken tree weeks after the onset demonstrated abscess formation between the
      soleus and gastrocnemius muscles. Slight high intensity indicating scar formation
      remained in the area of the former abscess six weeks after the onset. MRI was
      very useful not only in making the early diagnosis but also in the follow-up of
      pyomyositis.

PMID- 8521642
TI  - [A case of myotonic dystrophy with impairment of smooth pursuit eye movement].
AB  - We reported a 36-year-old woman of myotonic dystrophy with impairment of smooth
      pursuit eye movement. The patient, whose mother was also affected, had
      psychomotor retardation from childhood. DNA analysis by Southern hybridization
      technique showed large DNA fragment (14/8.6 kb). Oculomotor limitation and gaze
      nystagmus were not observed, and saccadic eye movements were normal. In
      electrooculography, smooth pursuit eye movements were impaired toward both
      directions, and interrupted by saccades. The caloric test elicited a satisfactory
      response, but the visual suppression test produced no suppression. CT scan
      displayed paraventricular low density area, and MRI showed the multiple foci of
      high signal intensity in the white matter on T2-weighted images. No changes were
      detected on CT or MRI in the brainstem and cerebellum. The lesions in the brain
      are considered to be correlated with smooth pursuit impairment.

PMID- 8521643
TI  - [A case of Guillain-Barre syndrome associated with anti-GM2 antibody due to
      cytomegalovirus infection--special reference to the effect of ganciclovir].
AB  - We report a case of Guillain-Barre syndrome (GBS) associated with anti-GM2
      antibody caused by cytomegalovirus (CMV) infection. A 27-year-old man was
      admitted to our hospital because of muscle weakness in all his extremities. He
      had no background of immunological abnormalities. Within 5 days, generalized
      muscular weakness had progressed so rapidly that he suffered respiratory
      dysfunction and dysphagia. Throughout the entire clinical course, enzyme
      immunoassay (serum) and enzyme-linked immunosorbent assay (CSF) for CMV were
      carried out serially. Only antibodies against CMV were elevated during the
      clinical course in the serum and CSF. These findings supported the idea that he
      had developed GBS due to isolated CMV infection. We examined the reactivity of
      GBS sera with crude ganglioside fraction, and only anti-GM2 antibody was
      recognized on a high-performance thin-layer chromatogram plate in this case.
      Although the anti-GM2 antibody was decreased transiently by plasmapheresis, the
      clinical symptoms progressed. The symptoms advanced very rapidly during high-dose
      gammaglobulin therapy associated with reelevation of the anti-GM2 antibody.
      Following ganciclovir administration, however, the symptoms became diminished
      within 7 days and the anti-GM2 antibody fell dramatically. We speculate that the
      reason for the observed effectiveness of ganciclovir was direct suppression of
      activation of CMV, followed by the inhibition of the production of demyelinating
      antibodies including the anti-GM2 antibody.

PMID- 8521644
TI  - [A case of hereditary pressure-sensitive neuropathy, confirmed by a gene
      analysis].
AB  - A 21-year-old male patient with hereditary pressure-sensitive neuropathy (HPSN)
      is reported. He had been well and was working as a carpenter until February 6,
      1993, when he developed difficulty in raising his left arm and numbness in the
      radial aspect of his left forearm in the morning. Left musculocutaneous nerve
      palsy, a left winged-scapula, absence of the left biceps and right Achilles
      reflexes, and distal dominant nerve conduction delay were positive findings. His
      father and younger brother showed similar conduction delays. Sural nerve biopsy
      revealed the presence of tomacula, segmental demyelination and thinly myelinated
      fibers. Gene analyses of the patient's cultured lymphoblastoid cells disclosed
      deletion of the marker 6G1 and peripheral myelin protein-22 (PMP-22) gene of a
      single allele of chromosome 17 in 90% of his intermitotic cells by in situ
      hybridization, and also a 57% gene dosage of PMP-22 of normal control using
      Southern blotting. These findings indicate the deletion in 17p11.2 of the genomic
      DNA of this patient, which is diagnostic for HPSN.

PMID- 8521645
TI  - [Changes of type IV collagen 7S and fibronectine in a patient with isolated ACTH
      deficiency].
AB  - A 60-year-old man presented with waste, muscle weakness and pain of knees and
      shoulders. Endocrinological investigations revealed low plasma cortisol and ACTH
      levels, delayed response of plasma cortisol to ACTH, no response of plasma ACTH
      to CRF and normal response to other pituitary hormone to corresponding stimulate
      test. He was diagnosed as isolated ACTH deficiency. Then we examined plasma type
      IV collagen 7S and fibronectin, because experimentally, corticosteroid regulates
      the extracellular matrix structure composed of type IV collagen, fibronectin and
      so on. These parameters were elevated and rapidly decreased to the normal range
      with the replacement of hydrocortisone, simultaneously his arthralgia was
      improved. These parameters can reflect the biochemistric change in cortisol
      deficiency state.

PMID- 8521646
TI  - [A case of bilateral upper medial medullary infarction].
AB  - A clinical case of bilateral upper medial medullary infarction was reported. A 61
      year-old woman was admitted to our hospital because of numbness of trunk and
      bilateral upper and lower limbs, aphonia and left-hemiparesis, which progressed
      to quadriplegia. Facial movements were intact. Her tongue was not fully protruded
      and deviated to the right side. Impairment of the position sense was noted in
      bilateral lower limbs. Respiratory failure was not observed. A brain MRI revealed
      a high-intensity area on T2-weighted imaging in the upper medulla oblongata. The
      lesion involved the medial medulla oblongata bilaterally. No lesions were present
      in the other brain parenchyma. According to the literature, respiratory failure
      was present in almost all patients with bilateral medial medullary infarction.
      The findings of our patient suggest that respiratory failure is not induced by
      the bilateral medial medullary infarction limited to the upper medulla oblongata.

PMID- 8521647
TI  - [A case of thrombocytopenia due to heparin therapy for a progressing ischemic
      stroke].
AB  - A 44-year-old man was admitted, complaining of weakness of his left limbs. On
      admission, he was oriented and cooperative. He showed positive Barre sign only on
      the left leg. Deep tendon reflexes were unremarkable; pathological reflexes were
      negative. There was no cerebellar ataxia or sensory deficit. Immediately after
      admission, monoplegia of the left leg progressed. He was started on heparin
      infusion therapy. His paralysis had been resolved by the 5th day. MRI of the
      brain demonstrated an infarction involving the body of the corpus callosum, the
      right cingulate gyrus, and the right paracentral lobule. Neuropsychologic
      examination demonstrated a disturbance of interhemispheric transfer of position.
      On the 10th day he developed Klebsiella ozaenae bacteremia. On the 11th day,
      platelet count was 9.2 x 10(4)/microliter. Antithrombin III, thrombin
      antithrombin III complex, D-dimer, and FDP levels were unremarkable, which is
      quite atypical for DIC associated with bacterial infection. Platelet factor 4 and
      beta-thromboglobulin levels were remarkably high, suggesting activated platelet
      aggregation. We made a diagnosis of heparin-induced thrombocytopenia and
      discontinued heparin infusion. Three days later, platelet count began to increase
      and creatinine levels returned normal. All patients receiving heparin should be
      monitored for platelet count.

PMID- 8521648
TI  - [Wallenberg's syndrome following minor neck trauma: a case associated with
      atlanto-axial subluxation, an anomaly of the axis, and platelet activation].
AB  - A 38-year-old man hit his forehead against a steel pipe, which made his neck
      hyperextended. He noticed unsteady gait and dysphagia approximately 6 hours after
      the accident. On the next day he was admitted. He had a Horner's syndrome, and
      pharyngeal and palatal weakness on the right side. There were no pyramidal tract
      signs. He could not balance on his right foot or gait tandemly. Sensation for
      cold and pin-prick was absent on his left limbs; position sense was intact.
      Angiography demonstrated an occlusion of the right vertebral artery at the 3rd
      segment. Cranial MRI demonstrated an infarction in the right lateral medulla. A
      radiogram demonstrated an atlanto-axial instability. There was an anomalous bone
      mass between the left superior articular process and the odontoid process. These
      abnormalities might have precipitated injury of the vertebral artery during the
      minor neck trauma. The plasma levels of molecular markers for coagulation and
      fibrinolysis were unremarkable. In contrast, beta-thromboglobulin and platelet
      factor 4 levels were high, suggesting activated platelet aggregation. To my
      knowledge, this is the first report showing evidence for platelet activation at
      the molecular level early in the course of vertebral artery thrombosis following
      a minor neck trauma.

PMID- 8521649
TI  - Heterotopic ossification mimicking infection. Scintigraphic evaluation.
AB  - Heterotopic ossification is a disorder of unknown etiology characterized by bone
      formation in the mesenchymal tissues. It occurs most commonly in patients who
      have had traumatic brain injury, spinal cord injury, or joint trauma or surgery.

PMID- 8521650
TI  - Reversible Tc-99m diphosphonate uptake in gastric tissue associated with
      malignancy related hypercalcemia. A comparative study using PET FDG whole body
      imaging.
AB  - A 52-year-old man with metastatic poorly differentiated bronchogenic carcinoma
      and serum calcium levels as high as 14.6 had intense Tc-99m MDP uptake found
      throughout the stomach wall on SPECT imaging. FDG uptake assessed by PET imaging
      was not elevated in the stomach, whereas multiple hyper-metabolic tumor foci
      could be found throughout the body. Three months later, when calcium levels
      normalized, no Tc-99m MDP uptake was found in the stomach despite persistence of
      neoplastic lesions elsewhere. This case study indicates that gastric MDP uptake
      in patients with malignancy related hypercalcemia can be reversible and not
      necessarily indicative of neoplastic infiltration.

PMID- 8521651
TI  - Delayed massive soft tissue uptake of Tc-99m MDP after radiation therapy for
      cancer of the breast.
AB  - A patient with a history of breast cancer and known lung metastases was referred
      for a bone scan to investigate the cause of severe neck and right shoulder pain.
      The bone scan showed massive uptake of the radiopharmaceutical in the soft tissue
      surrounding the right shoulder. A review of the patient's history indicated that
      the patient had undergone radiation therapy to the right upper thorax and breast
      area 14 months previously and an acute radiation dermatitis of the proximal right
      arm and should had developed. This had long since resolved. Physical examination
      and plain radiographs of the right shoulder and humerus failed to demonstrate any
      abnormality.

PMID- 8521652
TI  - Tc-99m nanocolloid and Tc-99m MDP three-phase bone imaging in osteomyelitis and
      septic arthritis. A comparative study.
AB  - The aim of this study was to compare Tc-99m nanocolloid scintigraphy with Tc-99m
      MDP bone imaging in the diagnosis of osteomyelitis and septic arthritis. Overall,
      31 Tc-99m MDP bone scans and 39 Tc-99m nanocolloid studies were performed in 34
      patients (15 female, 19 male; mean age, 14.88 years +/- 19.00 years) who were
      suspected of osteomyelitis and/or septic arthritis. The final diagnoses were
      established by needle aspiration, cultures, radiography, clinical course, and, in
      some patients, with CT, ultrasonography, and biopsy. The sensitivity,
      specificity, and accuracy were 100%, 75%, and 92%, respectively for both Tc-99m
      MDP and Tc-99m nanocolloid scans in detecting osteomyelitis. For septic
      arthritis, Tc-99m MDP bone imaging showed 100%, 85%, and 94%, and Tc-99m
      nanocolloid scans showed 90%, 59%, and 76%, sensitivity, specificity, and
      accuracy, respectively. These results show that, although both scans are in good
      agreement for osteomyelitis, for septic arthritis nanocolloid is not specific
      enough to recommend it to be a complementary method to MDP bone scans.

PMID- 8521653
TI  - Quantitative measurement of vascularization and vascular ingrowth rate of
      coralline hydroxyapatite ocular implant by Tc-99m MDP bone imaging.
AB  - Complete fibrovascular ingrowth of the hydroxyapatite ocular implant is necessary
      for peg drilling, the secondary procedure that couples the mobile sphere to the
      ocular prosthesis providing it with motility. This study was conducted to
      determine the usefulness of the bone scan for the evaluation and relative
      quantification of the vascularization of coralline hydroxyapatite ocular
      implants. In 23 patients (32 scans), vascularization of the ocular implant was
      measured by three-phase bone scintigraphy. There were 16 patients with left, and
      7 with right orbital implants. At followup 0.5 to 8 months after successful
      hydroxyapatite implantation, the mean implant to normal intraorbital activity
      ratio on delayed bone scans in anterior view was 2.73 +/- 0.73 (mean +/- SD) with
      a range of 1.42-4.2. The normal right to left and left to right intraorbital bone
      activity ratios determined in anterior view from 10 normal delayed bone scans
      were 0.98 +/- 0.05 (mean +/- SD) and 1.02 +/- 0.05 (mean +/- SD) respectively,
      with a range of 0.93-1.07. The difference of the activity (count) ratios among
      the successfully implanted group and normals was statistically significant (P <
      0.0001). A hydroxyapatite ocular implant to contralateral intraorbital bone
      activity ratio of greater than 1.12 with a homogeneous tracer distribution
      throughout the implant suggests adequate and diffuse vascularization is present.
      The progressive increase in activity ratio of the orbital implants seen in the
      early postimplantation period, which is indicative of the progression of
      vascularization, reaches a plateau after 1 month and remains relatively stable
      thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521654
TI  - Diminished Tc-99m HMPAO pulmonary uptake in ex-smokers.
AB  - Normally, there is no localization of Tc-99m HMPAO in the lungs. Tc-99m uptake in
      smokers' lungs has been reportedly higher than in nonsmokers. Thus, the lung
      uptake may be used as a barometer of cigarette smoking. To assess whether there
      is a decrease in pulmonary uptake of Tc-99m HMPAO after cessation of smoking, the
      authors investigated the lung uptake of 31 male ex-smokers in comparison to
      smokers and nonsmokers. Anterior and posterior images were taken 10 minutes after
      intravenous injection of 20-25 mCi of Tc-99m HMPAO. Regions-of-interest over the
      liver and lungs in the anterior view were calculated. Duration of abstinence from
      smoking ranged from 5 months to 50 years. The mean lung/liver uptake in ex
      smokers was 0.489 +/- 0.019 (sem). In a previous report, the mean lung/liver
      ratio for smokers (N = 30) was 0.805 +/- 0.040 (sem) and 0.408 +/- 0.019 (sem)
      for nonsmokers (N = 25). Compared with smokers, the lung/liver uptake ratio of ex
      smokers was significantly lower (P < 7 x 10(-9)). The lung/liver uptake ratio of
      ex-smokers was significantly higher than that of nonsmokers (P < 0.005). The
      authors conclude that pulmonary Tc-99m HMPAO uptake of smokers is significantly
      diminished after quitting smoking. However, the lung uptake of ex-smokers is
      higher than that of non-smokers. The uptake in the lung induced by smoking
      appears to be partially reversible after the cessation of smoking.

PMID- 8521655
TI  - Prediction of pulmonary function after resection of primary lung cancer. Utility
      of inhalation-perfusion SPECT imaging.
AB  - To help determine whether preoperative perfusion and inhalation SPECT imagings
      are useful in predicting postoperative lung function, Tc-99m MAA perfusion SPECT
      imaging, CT scans, and pulmonary function tests were prospectively performed in
      33 patients with primary lung cancer before and after lobectomy or pneumonectomy.
      Tc-99m Technegas inhalation SPECT imaging was performed in 6 of 33 patients as
      well. The authors also studied changes in radioactivity on the operated and
      nonoperated sides before and after surgery, examined the lowest limit value for
      adaptability to the operation, and made a comparison of both perfusion and
      inhalation SPECT imaging. The predicted postoperative values obtained from the
      preoperative Tc-99m MAA SPECT images correlated more closely with the measured 6
      month postoperative values than with the measured 3-month postoperative values.
      The highest correlation coefficient (r = 0.86) was observed between the predicted
      forced vital capacity (FVC) value and the measured 6-month postoperative FVC
      value. In many cases, there was not a great difference between the 6-month and 3
      month radioactivity on the operated side obtained from Tc-99m MAA SPECT images.
      This appears to indicate that pulmonary blood flow on the operated side has
      completely recovered by 3 months after surgery. However, radioactivity in both
      the upper and lower lobes of the nonoperated side increased soon after surgery
      compared with that before the operation, and had not returned to preoperative
      levels 6 months after surgery. The radioactivity in the right middle lobe did not
      change before and after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521656
TI  - Comparison of TI-201 and Tc-99m MIBI SPECT imaging in nasopharyngeal carcinoma.
AB  - Both TI-201 and Tc-99m MIBI uptake in nasopharyngeal carcinoma (NPC) have been
      reported, yet no comparative study of these two agents using SPECT images has
      been undertaken for NPC. This study compares the relative effectiveness of TI-201
      and Tc-99m MIBI SPECT for detecting NPC. In the patients with NPC, 26 of 32 (81%)
      showed TI-201 tumor uptake, whereas 24 of 32 (75%) showed Tc-99m MIBI tumor
      uptake. This preliminary study suggests that both Tc-99m MIBI and TI-201 SPECT
      imaging can be helpful in detecting NPC, and that sensitivity is slightly higher
      in TI-201 SPECT imaging.

PMID- 8521657
TI  - Tc-99m HMPAO brain SPECT compared to CT and EEG after seizures in childhood.
AB  - Twenty-one children with various seizure disorders were studied using Tc-99m
      HMPAO brain SPECT, cranial CT, and electroencephalography (EEG). The rates of
      pathologic findings on SPECT, CT, and EEG were 67%, 38%, and 52%, respectively.
      SPECT showed congruent, or more extensive, lesions in all eight patient with CT
      lesions. Six of the 13 children who had normal CT results, had abnormal SPECT
      study results. In this postictal series, 4 of the 14 abnormalities detected in
      the first SPECT study that was applied within 24 hours of a seizure, were in the
      form of hyperperfused areas. Eight of the 14 abnormal first SPECT studies had
      become normal by the second SPECT. We conclude that, with respect to the
      depiction of some kind of abnormality, HMPAO brain SPECT is superior to CT and
      EEG, and considerable changes in brain perfusion are likely to occur over a
      period of a few weeks.

PMID- 8521658
TI  - Evaluation of cerebral blood flow in patients with idiopathic orthostatic
      hypotension using Tc-99m HMPAO brain SPECT during postural testing.
AB  - To determine whether regional cerebral blood flow (rCBF) would change on standing
      in patients with idiopathic orthostatic hypotension (IOH), Tc-99m HMPAO SPECT
      studies were performed during postural testing in five patients with IOH. After
      10 minutes of quiet rest on a bed, the patients arose quickly and, at the same
      time, the radiotracer was injected intravenously. SPECT data were obtained with a
      ring-type SPECT scanner. Another dose of Tc-99m HMPAO was injected with the
      subjects in the supine position, and SPECT was performed again. Image subtraction
      was used to evaluate the change in rCBF caused by postural testing. In all
      patients, the authors observed a decrease of rCBF ni the frontal cortex and basal
      ganglia. This preliminary study suggests that changes in rCBF occur in patients
      with IOH on standing, and Tc-99m HMPAO SPECT performed during postural testing
      may have an important role in evaluating these changes.

PMID- 8521659
TI  - Moyamoya disease in twins.
AB  - Tc-99m HMPAO SPECT was used to evaluate regional blood flow in one monozygotic
      twin who had angiographically proven moyamoya disease. Focal and global reduced
      regional cerebral perfusion were observed in both patients with Tc-99m HMPAO
      SPECT studies. There was good correlation between the localization and degree of
      regional cerebral blood flow abnormalities and the severity and stage of clinical
      symptoms on angiography. These results suggest that Tc-99m HMPAO SPECT is a
      useful method in the detection of hemodynamic abnormalities in moyamoya disease.

PMID- 8521660
TI  - Labeled WBC cardiac imaging and two-dimensional echocardiography to evaluate high
      dose gamma globulin treatment in Kawasaki disease.
AB  - Twenty-eight children (5 girls, 23 boys; age, 20.3 +/- 16.2 months) with Kawasaki
      disease (KD) were included in this study. The children were treated with aspirin
      plus intravenous injection of gamma globulin (IVGG). Both Tc-99m HMPAO labeled
      WBC heart imaging (Tc-WBC) and two-dimensional echocardiograms (2D-Echo) were
      used to evaluate the effects of IVGG on the most common cardiac presentations-
      carditis and dilated coronary arteries--in KD. After IVGG therapy, the results
      showed that 32.1% (9/28) carditis patients had improved; 39.3% (11/28) of
      patients had no significant change; 28.6% (8/28) of patients had severe changes,
      and there was no significant difference among the three groups by the evidences
      of Tc-WBC. Dilated coronary arteries (CA) became smaller in 32.1% (9/28) of
      patients; 53.6% (15/28) of patients had no definite change; 14.3% (4/28) of
      patients had dilated LCA that became larger; and borderline difference existed
      among the three groups, proved by 2D-Echo. Between the Tc-WBC and 2D-Echo, 35.7%
      (10/28) of patients had similar changes, and 64% (18/28) of patients showed
      incongruous changes; and there was little difference. In conclusion, Tc-WBC and
      2D-Echo provide strong evidence of the existence of carditis and dilated coronary
      arteries in certain patients, even after IVGG treatment. The improvements of
      carditis and dilated coronary arteries were not correlated with each other after
      IVGG therapy.

PMID- 8521661
TI  - Nuclear medicine imaging in a case of hyperfunctioning parathyroid carcinoma
      associated with a parathyroid adenoma.
AB  - This report describes a rare case of parathyroid carcinoma associated with an
      adenoma. Nuclear imaging provided the most specific information about
      localization of the primary carcinoma and cervical metastasis, but failed to
      demonstrate evidence of a parathyroid adenoma. This could be explained by a
      partial inhibition of hormonal biosynthesis due to the high level of circulating
      parathormone produced by the carcinoma.

PMID- 8521662
TI  - An atlas of renography with Tc-99m sestamibi: comparison with Tc-99m DTPA.
AB  - Tc-99m sestamibil demonstrates considerable renal uptake followed by net urinary
      clearance similar to that of creatinine. The authors have previously shown that
      renograms could be obtained in cardiac patients by imaging during the rest
      injection of the perfusion agent. The present study shows correlating Tc-99m
      sestamibi and Tc-99m DTPA studies in hypertensive patients with a spectrum of
      findings, including aortic aneurysms, asymmetry due to renovascular disease,
      cysts, bilateral renal dysfunction, and horseshoe kidney. Tc-99m sestamibi images
      have persisting background activity in the liver and spleen, but show renal
      structure and function in adequate detail. Quantitative analysis confirms that Tc
      99m sestamibi has higher renal uptake, but less excretion than Tc-99m DTPA.
      Review of these correlating studies suggests straightforward transfer of
      diagnostic expertise with standard renography to this new application.

PMID- 8521663
TI  - "Double chamber" right ventricle due to prominent trabeculation.

PMID- 8521664
TI  - Hot calcaneus on three-phase bone scan due to bone bruise.

PMID- 8521665
TI  - Tl-201 uptake in pulmonary Mycobacterium avium complex infection.

PMID- 8521666
TI  - False appearance of urinary stasis on Tc-99m MAG3 renal scan secondary to
      vicarious tracer concentration in the gallbladder.

PMID- 8521667
TI  - Simultaneous hot and cold bone scan metastases in hepatocellular carcinoma.

PMID- 8521668
TI  - Renal scintigraphy in the diagnosis of aortic dissection affecting the renal
      arteries.

PMID- 8521669
TI  - Brain SPECT imaging with Tc-99m HMPAO in hepatic encephalopathy.

PMID- 8521670
TI  - An anatomy lesson by Sir James Paget.

PMID- 8521671
TI  - Splenic lymphangioma. An unusual manifestation of the Klippel-Trenaunay-Weber
      syndrome.

PMID- 8521672
TI  - Arterial thromboembolism after catheterization.

PMID- 8521673
TI  - Pulmonary vessel involvement in Takayasu arteritis.

PMID- 8521674
TI  - Metastatic calcification. Difference of uptake between Tc-99m HMDP and Ga-67
      citrate.

PMID- 8521675
TI  - Current readings in nuclear medicine.

PMID- 8521676
TI  - Input from the deep south compartment. A personal viewpoint.

PMID- 8521677
TI  - Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic
      implications.
AB  - Zolpidem is an imidazopyridine which differs in structure from the
      benzodiazepines and zopiclone. It is a strong sedative with only minor
      anxiolytic, myorelaxant and anticonvulsant properties, and has been shown to be
      effective in inducing and maintaining sleep in adults. The available evidence
      suggests that zolpidem produces no rebound or withdrawal effects, and patients
      have experienced good daytime alertness. Zolpidem 10mg in non-elderly and a
      reduced dose of 5mg in elderly individuals are clinically effective. In humans,
      the major metabolic routes include oxidation and hydroxylation; none of the
      metabolites appears to be pharmacologically active. The pharmacological activity
      of zolpidem results from selective binding to the central benzodiazepine
      receptors of the omega 1 subtype. Zolpidem is approximately 92% bound to plasma
      proteins; absolute bio-availability of zolpidem is about 70%. After single 20mg
      oral doses, typical values of pharmacokinetic variables for zolpidem in humans
      are: a peak plasma concentration of 192 to 324 micrograms/L occurring 0.75 to 2.6
      hours postdose; a terminal elimination half-line of 1.5 to 3.2 hours; and total
      clearance of 0.24 to 0.27 ml/min/kg. Zolpidem pharmacokinetics are unchanged
      during multiple-dose treatment. Zolpidem pharmacokinetics are not significantly
      influenced by gender. Clearance of zolpidem in children is 3 times higher than in
      young adults, and is lower in very elderly people. There are no significant
      differences in the pharmacokinetic parameters between various racial groups.
      Dosage reduction appears to be prudent in patients with renal disease, and
      caution should be exercised when prescribing zolpidem to elderly patients with
      hepatic impairment. Coadministration of haloperidol, cimetidine, ranitidine,
      chlorpromazine, warfarin, digoxin or flumazenil do not alter the pharmacokinetics
      of zolpidem; flumazenil predictably antagonises the hypnotic effects of zolpidem.
      Alertness tends to be reduced when cimetidine is combined with zolpidem.
      Volunteers treated with imipramine plus zolpidem developed anterograde amnesia.

PMID- 8521678
TI  - Antidepressant toxicity and the need for identification and concentration
      monitoring in overdose.
AB  - Antidepressant drugs are among the most commonly encountered causes of self
      poisoning. These drugs include tricyclics, tetracyclics, bicyclics and
      monocyclics, as well as monoamine oxidase (MAO) inhibitors and selective
      serotonin reuptake inhibitors (SSRIs). Of these, the tricyclic antidepressants
      (TCAs) are generally more toxic in overdose, with major toxicity usually
      manifesting within the first 6 hours after overdose. Various studies indicate
      that patients at risk of toxicity from TCA overdose may be identified by
      neurological, cardiovascular and electrocardiography status, together with a
      quantitative estimate of the plasma drug concentration. While there are various
      methods available for such chemical estimations, the most satisfactory appears to
      be fluorescence polarisation immunoassay which gives rapid quantitative results
      for a variety of TCAs. The selective MAO-A inhibitor antidepressants and the
      SSRIs are relatively nontoxic when taken alone. However, overdoses of
      combinations of MAO inhibitors and either SSRIs or TCAs with serotonin reuptake
      blocking activity may result in a serotonin syndrome with a severe or fatal
      outcome. Features of this syndrome include hyperpyrexia, disseminated
      intravascular coagulation, convulsions, coma and muscle rigidity, which may not
      develop until 6 to 12 hours after overdose. While quantitative chemical
      identification of these drugs following overdose is helpful in confirming the
      diagnosis, it is not mandatory. The increasing use of MAO-A inhibitors and SSRIs
      in the treatment of depression suggests that careful clinical observation is
      required when combination overdoses are suspected.

PMID- 8521681
TI  - Management of the Rh-sensitized mother.
AB  - The approval by the FDA of Rh immune globulin in 1968 led to a decrease in the
      incidence of Rh isoimmunization. As a result, fewer cases are seen by both the
      perinatologist and neonatologist. Prompt identification and early referral of the
      isoimmunized mother to a tertiary center will facilitate optimal management
      incorporating the latest techniques. In selected clinical situations, the less
      invasive technique of amniocentesis can be offered in place of fetal blood
      sampling for Rh D typing. In the anemic fetus requiring intrauterine
      transfusions, delivery is the goal once lung maturity is documented. As described
      elsewhere in the issue, recent improvements in neonatal care have facilitated
      management of complications not seen in the fetus but potentially critical in the
      neonate.

PMID- 8521682
TI  - Management of neonatal Rh disease.
AB  - Dramatic improvements have been made in the management of Rh disease. Anti-D
      immune globulin has reduced the incidence of Rh sensitization. Intrauterine
      transfusions have become routine to treat fetal anemia. Once an affected infant
      is born, several recent improvements in neonatal care have aided in the treatment
      of hyperbilirubinemia. These include improved phototherapy, such as fiberoptic
      delivery systems, and intravenous immunoglobulin. Experience with heme oxygenase
      inhibitors is accumulating, and they may prove efficacious in Rh disease. Double
      volume (and perhaps single-volume) exchange transfusion remains an effective
      method to control hyperbilirubinemia when other therapies fail. Erythropoietin
      may have a role in treating late, hyporegenerative anemia. Finally, better ways
      to assess the risk of brain injury in patients with hyperbilirubinemia may become
      available. Cooperation between the obstetric and neonatal teams to treat Rh
      sensitized mothers and their babies is essential.

PMID- 8521680
TI  - Geographical/interracial differences in polymorphic drug oxidation. Current state
      of knowledge of cytochromes P450 (CYP) 2D6 and 2C19.
AB  - The isoenzymes which catalyse the polymorphic hydroxylations of
      debrisoquine/sparteine and S-mephenytoin are cytochromes P450 2D6 and P450 2C19
      (CYP2D6 and CYP2C19), respectively. CYP2D6 is involved in the stereospecific
      metabolism of several important groups of drugs, for example antiarrhythmics,
      antidepressants and neuroleptics. About 7% of Caucasians but only 1% of Orientals
      are poor metabolisers (PMs) of debrisoquine. The most common mutated allele
      CYP2D6B in Caucasian PMs is almost absent from their Oriental counterparts. On
      the other hand, the mean activity of CYP2D6 in Oriental extensive metabolisers
      (EMs) is lower than that in Caucasian EMs. This is due to the frequent
      distribution of a partially deficient CYP2D6 allele causing a Pro34-->Ser amino
      acid exchange in as many as 50% of Oriental alleles. This is the molecular
      genetic basis for slower metabolism of antidepressants and neuroleptics observed
      in Oriental compared with Caucasian people, and consequently for the lower
      dosages of these drugs used. While CYP2D6 catalyses the metabolism of lipophilic
      bases only, CYP2C19 is involved in the metabolism of acids (e.g. S-mephenytoin),
      bases (e.g. imipramine and omeprazole) and neutral drugs (e.g. diazepam). About
      3% of Caucasians and 12 to 22% of Orientals are PMs of S-mephenytoin. Polymerase
      chain reaction-based genotyping techniques recently became available for the two
      CYP2C19 mutated alleles m1 and m2, which cause no enzyme to be expressed. M1
      accounts for about 80% of the mutations responsible for the PM phenotypes in
      Caucasians, Oriental and Black people. Diazepam is partially demethylated by
      CYP2C19, and the high frequency of mutated alleles in Orientals is probably the
      reason why such populations have a slower metabolism and are treated with lower
      doses of diazepam than Caucasians. Omeprazole is to a major extent hydroxylated
      by CYP2C19, and there is an approximately 10-fold difference in oral clearance
      between EMs and PMs of S-mephenytoin. The separation of Caucasians from Orientals
      is fairly recent in the evolutionary process (40,000 to 60,000 years ago); the
      separation of Black from Caucasian/Oriental people occurred much earlier, about
      150,000 years ago. As pronounced differences have been found between Caucasians
      and Orientals in the CYP2D6 and CYP2C19 enzymes, it might be expected that Black
      people will show even greater differences in this respect. Some studies have been
      performed with Black participants, but the picture is not clear. The mean CYP2D6
      activity in Black EMs seems to be lower than that in Caucasian EMs and similar to
      that of Oriental EMs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8521683
TI  - Anemia of pregnancy.
AB  - A general work-up for anemia during pregnancy could follow a simplified flow
      diagram, such as the one shown in Figure 1. More specific laboratory tests should
      be selected as needed.

PMID- 8521679
TI  - Clinical relevance of drug interactions with lithium.
AB  - Although lithium continues to be regarded as the treatment of choice for bipolar
      disorders, the clinical use of this mood stabiliser is associated with an
      extremely narrow therapeutic range. Relatively minor increases in serum
      concentrations may induce serious adverse sequelae, and concentrations within the
      therapeutic range may result in toxic reactions. The safety of combining lithium
      with other medications, therefore, is a major concern, and extensive clinical
      experience has served to identify several significant drug interactions. Lithium
      removal from the body is achieved almost exclusively via renal means. As a
      result, any medication that alters glomerular filtration rates or affects
      electrolyte exchange in the nephron may influence the pharmacokinetic disposition
      of lithium. Concomitant use of diuretics has long been associated with the
      development of lithium toxicity, but the risk of significant interactions varies
      with the site of pharmacological action of the diuretic in the renal tubule.
      Thiazide diuretics have demonstrated the greatest potential to increase lithium
      concentrations, with a 25 to 40% increase in concentrations often evident after
      initiation of therapy. Osmotic diuretics and methyl xanthines appear to have the
      opposite effect on lithium clearance and have been advocated historically as
      antidotes for lithium toxicity. Loop diuretics and potassium-sparing agents have
      minor variable effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also
      been associated with lithium toxicity, although the relative interactive
      potential of specific NSAIDs is difficult to determine. Small prospective studies
      have demonstrated large interindividual differences in lithium clearance values
      associated with different NSAIDs. A growing body of evidence also suggests that
      ACE inhibitors may impair lithium elimination, but further investigations are
      needed to identify patients at risk. Anecdotal reports have linked numerous
      medications with the development of neurotoxicity without an apparent effect on
      the pharmacokinetic disposition of lithium. Antipsychotics, anticonvulsants and
      calcium antagonists have all be implicated in a sufficient number of case reports
      to warrant concern. As these medications have all been commonly coadministered
      with lithium, the relative risk of serious interactions appears to be quite low,
      but caution is advised.

PMID- 8521684
TI  - The physiologic impact of anemia in the neonate.
AB  - Clinically useful indicators of physiologically significant anemia requiring
      intervention have yet to be defined in the newborn. Finding a simple noninvasive
      marker of physiologically significant anemia remains elusive but is a laudable
      goal considering the risks of transfusion therapy and requirement for repeated
      parenteral (subcutaneous or IV) administration or r-HuEPO, when chosen as a
      preventive or therapeutic option. The asymptomatic newborn has shown considerable
      tolerance to anemia without detrimental effects and need for an iatrogenic
      increase in RBC mass. Newer guidelines for transfusion are emerging that lower
      the threshold hematocrit and hemoglobin concentration at which RBC transfusion
      may be considered. Following those guidelines alone may decrease the need for
      transfusion and improve our understanding of the physiologic impact of anemia in
      the neonate. Ongoing investigation in understanding better the physiologic impact
      and consequences of anemia is critical in that regard.

PMID- 8521685
TI  - Recombinant human erythropoietin in neonatal anemia.
AB  - Recombinant human erythropoietin (r-HuEPO) is a new therapeutic modality for the
      treatment of neonatal anemia. The results of three large controlled trials were
      published within the past year. This article reviews the physiologic rationale
      underlying the use of r-HuEPO in preterm infants, addresses how the design of
      clinical trials affects outcomes and conclusions, and discusses the recent trials
      in this context. The article concludes with a summary of questions that require
      further investigation.

PMID- 8521686
TI  - Red blood cell transfusion practices in the neonate.
AB  - Premature infants, particularly those with a birthweight of less than 1.0
      kilograms and respiratory disease, frequently require red blood cell (RBC)
      transfusions. The major mechanisms causing the anemia of prematurity are
      phlebotomy blood losses and a diminished ability to mount an effective
      erythropoietin response to the falling RBC mass. Although the indications for RBC
      transfusions have not been defined by controlled clinical trials, usual
      transfusion practices are discussed. In addition, the potential role for
      recombinant erythropoietin in the treatment of anemia of prematurity is analyzed
      critically. Finally, an overall approach to managing the anemia of prematurity is
      provided.

PMID- 8521687
TI  - Minimizing donor blood exposure in the neonatal intensive care unit. Current
      trends and future prospects.
AB  - Limitations in the knowledge of the pathophysiology of anemia contribute to
      unfounded and liberal transfusion practices in the preterm infant and to
      uncertain risk-benefit ratios. Researchers have explored an array of strategies
      to minimize transfusions. Such strategies include collection and banking of
      autologous placental blood, administration of recombinant erythropoietin,
      innovations in blood banking practices, and improved definitions of the markers
      of anemia with more rigorous transfusion guidelines. This article presents an
      overview of these and other strategies that can be applied as part of an overall
      approach to limit effectively the number of transfusions in the newborn.

PMID- 8521688
TI  - Nutritional anemias in infancy.
AB  - Anemia in the 1st year of life should be an important warning sign to the
      clinician of a potential underlying nutritional deficiency. Prompt diagnosis and
      treatment are warranted in many cases, not only to treat the anemia but also,
      more important, to prevent other long-term sequelae associated with the
      underlying, causative deficiency. As more information about the impact of
      nutrition on various aspects of health is collected and newer therapies for the
      treatment of disease are developed, it will be important to understand and
      consider the role of vitamins and minerals in a light beyond the realm of
      nutritional anemia.

PMID- 8521689
TI  - Neonatal polycythemia and hyperviscosity.
AB  - The neonatal polycythemia/hyperviscosity syndrome continues to perplex the
      pediatrician. Although it is reasonably common, with an incidence of 1% to 5%,
      significant symptoms are less frequent and may be more due to predisposing
      factors such as perinatal asphyxia, intrauterine hypoxia, or hypoglycemia.
      Infants who are small for gestational age or affected by maternal gestational
      diabetes are at high risk for the disorder. Partial exchange transfusion used to
      lower hematocrit will decrease viscosity, reverse many of the physiologic
      abnormalities, and ameliorate most symptoms, but has not been shown to
      significantly impact the long-term outcomes of these children.

PMID- 8521690
TI  - Neutropenia in the neonate.
AB  - Neutropenia, a below normal concentration of neutrophils in the circulating
      blood, can be the kinetic result of diminished neutrophil production, excessive
      neutrophil margination, or accelerated neutrophil utilization and destruction.
      The significance of neutropenia to the well-being of the subject is dependent, in
      part, on the responsible kinetic mechanism. In this review of the causes of
      neutropenia in newborn infants, the authors examine neutrophil production and
      kinetics in the human fetus and newborn infant. The recognized causes of
      neutropenia in neonates are categorized and discussed according to their
      underlying kinetic mechanism.

PMID- 8521691
TI  - Advances in the diagnosis and treatment of neonatal hyperbilirubinemia.
AB  - Many controversies remain regarding the role of bilirubin in the developing
      human. Although kernicterus and cognitive impairment have been linked to
      hyperbilirubinemia, more recent studies have suggested that there might actually
      be beneficial effects of bilirubin at a cellular level; thus, the need to better
      understand the molecular and cellular physiology of this molecule is important.
      The attempted management of serum or tissue levels of bilirubin may either have
      implications for long-term neurologic development or interfere with normal body
      stress responses. Production of CO via heme catabolism also warrants further
      investigation regarding its role in cell to cell communication or in other
      important cellular reactions. New methods are being developed to better detect CO
      under a variety of experimental conditions, as well as to estimate total
      bilirubin production by measuring the COHb level of pulmonary excretion of CO.
      The development of new drugs to modulate bilirubin production is the subject of
      ongoing research. Although some metalloporphyrins already have been used
      clinically, the advantages and disadvantages of each drug still require further
      study. These new drugs are not only raising fascinating research questions about
      heme and bilirubin metabolism, but they may soon revolutionize the way we
      approach the diagnosis and management of neonatal jaundice, and provide new
      pharmacologic tools for exploring other aspects of metabolism.

PMID- 8521692
TI  - Vitamin K deficiency and hemorrhage in infancy.
AB  - Hemorrhage in the infant from vitamin K deficiency is still a concern in
      pediatrics. Vitamin K given intramuscularly will largely prevent hemorrhagic
      disease in the newborn, even in infants who are exclusively breast-fed and are
      thus at the greatest risk for bleeding. The vitamin K content of human milk is
      very low compared with standard infant formulas. Results with oral vitamin K
      prophylaxis, currently used in some countries following the association found in
      a single report between childhood cancer and intramuscular vitamin K, are far
      more controversial. Any role of vitamin K in the prevention of IVH in premature
      infants has not been sufficiently demonstrated. Ongoing developments in this
      field will lead to improved methods of detecting early vitamin K deficiency and
      perhaps suitable alternatives to intramuscular vitamin K prophylaxis in the
      newborn.

PMID- 8521693
TI  - Perinatal thrombocytopenia.
AB  - Maternal thrombocytopenia is common in normal pregnancies, but is a poor
      predictor of fetal thrombocytopenia even when the maternal thrombocytopenia is of
      pathologic etiology. The real risk to the fetus and the neonate is alloimmune
      thrombocytopenia, although identification of index cases is problematic and
      management of future pregnancies has not been defined.

PMID- 8521694
TI  - Hemolytic anemia in the newborn.
AB  - Evaluation of hemolytic anemia in the newborn may be complicated owing to the
      physiologic changes that occur during this time; however, the newborn period is a
      time when congenital red cell abnormalities may first present and when maternal
      factors need to be considered. In this article, an approach to the diagnosis of
      hemolytic disease in the newborn is reviewed. The unique properties of the
      neonatal red cell, the normal red cell changes present in the neonate, the
      potential congenital defects and maternal factors that may influence the
      associated clinical and laboratory findings consistent with the diagnosis of
      hemolytic anemia, and a brief review of the red cell disorders associated with
      hemolytic anemia in the newborn are discussed.

PMID- 8521695
TI  - Rigid bronchoscopy. The forgotten art.
AB  - Rigid bronchoscopy is superior to flexible fiberoptic bronchoscopy in several
      clinical situations. General anesthesia is usually used with side port
      ventilation. In children, removal of foreign bodies is an important indication.
      Tracheal stricture dilatation and cryotherapy are indications in adults, but
      laser bronchoscopy has become the major indication for rigid bronchoscopy in
      adult medicine.

PMID- 8521696
TI  - Endoscopic management of benign airway stenosis.
AB  - Endoscopic management of benign airway stenosis is successful in the majority of
      patients if patients are selected properly. Predictive anatomic features have
      been identified that aid patient selection. Moreover, mucosal sparing techniques
      should be used at all times. Given its clinical effectiveness and low
      complication rate, endoscopic management should remain the first option for
      subglottic and tracheal stenosis. Endoscopic management does not preclude the use
      of open surgical procedures if necessary. Future studies should be directed
      toward refining and optimizing the endoscopic operative technique.

PMID- 8521697
TI  - Laser bronchoscopy.
AB  - The worldwide epidemic of cancer of the lung has stimulated the development of
      therapies to relieve endobronchial obstruction. Table 3 lists a number of
      endobronchial therapies that might be used to treat malignant central airway
      obstruction. With over 15 years of worldwide experience, the Nd:YAG laser has
      proven to be the most important of these tools. Laser bronchoscopy can be
      performed with rigid or flexible instruments and produces a rapid recanalization
      of the airway with associated relief of symptoms. The treatment is repeatable and
      has acceptable immediate complications and infrequent delayed complications. To
      be effective, laser bronchoscopy can only be used for the treatment of
      intraluminal obstructions. Obstruction by submucosal infiltration and external
      compression require other endobronchial therapies. The performance of laser
      bronchoscopy requires an extra commitment by the bronchoscopist. A thorough
      understanding of airway and mediastinal anatomy is mandatory along with an
      appreciation of laser physics and tissue interaction. Attendance at specialized
      training courses may be required to satisfy local credentialing bodies. In the
      past 15 years, thousands of patients have benefited from the development of laser
      bronchoscopy techniques. No longer a therapy of last resort, laser bronchoscopy
      has proven to be an excellent tool to relieve the symptoms of central airway
      obstruction.

PMID- 8521698
TI  - Cryotherapy for tracheobronchial disorders.
AB  - Cryotherapy is the therapeutic application of extreme cold for local destruction
      of living tissue. This technique has been shown to be effective and safe in
      treating endobronchial lesions, particularly in patients with endobronchial
      carcinoma and airway obstruction. This article describes cryotherapy and its use
      in treating tracheobronchial disorders.

PMID- 8521699
TI  - Endobronchial brachytherapy.
AB  - Intraluminal endobronchial brachytherapy is a technique in which an encapsulated
      radioactive source is placed near a tumor for localized irradiation. It is
      effective, with or without other treatment modalities, in palliating problems
      caused by endobronchial malignancies, such as dyspnea, hemoptysis, cough,
      atelectasis, and postobstructive pneumonia. This article describes the different
      techniques and dosage schemes for brachytherapy, indications and
      contraindications, reported rates of efficacy and complications, and limitations
      of the technique.

PMID- 8521700
TI  - Photodynamic therapy. Its use in the management of bronchogenic carcinoma.
AB  - Photodynamic therapy is an investigational treatment of various types of
      carcinoma. It involves a photosensitizing agent which, when exposed to light of
      the proper wavelength, forms toxic oxygen radicals that result in cell death.
      This article describes its current use in the management of bronchogenic
      carcinoma.

PMID- 8521701
TI  - Airway stents. Present and future.
AB  - Tracheobronchial stent insertion is a relatively new technique used to palliate
      or cure central airways obstruction. When performed by experienced thoracic
      endoscopists, this procedure is both safe and effective, even if complications of
      indwelling stents may require repeat endoscopic intervention. Although proven
      clinically beneficial to many patients, airway prostheses have not yet been the
      subject of large comparative case studies or randomized controlled
      investigations. Reports are often experiential and anecdotal. Further research is
      needed to determine the effects of stenting on survival in patients with
      malignant airway disease and its degree of success in patients with benign airway
      strictures. Only then will airway stents truly deserve their place alongside
      other therapies for tracheobronchial obstruction.

PMID- 8521702
TI  - Medical thoracoscopy. Technical details.
AB  - In summary, thoracoscopy offers several possibilities for diagnostic and
      therapeutic uses. Thoracoscopy helps in the diagnosis of pleural-based malignancy
      or tuberculosis with a high degree of accuracy when routine studies and closed
      needle pleural biopsies have failed. In patients in whom adequate visualization
      is possible, an unequivocal pathological diagnosis of benign diseases can be made
      with a specificity approaching 100%. Thoracoscopy is effective in the management
      of malignant pleural effusion and spontaneous pneumothorax.

PMID- 8521703
TI  - Medical thoracoscopy. Role in pleural and lung diseases.
AB  - This overview of the indications for interventional thoracoscopy is far from
      exhaustive and new applications will surely be proposed. In conclusion,
      thoracoscopy provides diagnosis of pleural-based malignancy or tuberculosis with
      a high degree of accuracy when routine cytology and closed-needle pleural
      biopsies have failed. In patients in whom adequate visualization can be
      accomplished, an unequivocal pathologic diagnosis of benign disease can be made
      with a specificity approaching 100%. If transbronchial biopsy and bronchoalveolar
      lavage are inconclusive, VATS lung biopsy appears to be a safe alternative to
      open lung biopsy by thoracotomy for diagnosis of diffuse interstial or infectious
      lung disease. Thoracoscopy is often effective in the management of malignant
      pleural effusion and spontaneous pneumothorax. A close working relationship
      between pulmonary physicians and thoracic surgeons will assure that patients
      undergoing diagnostic thoracoscopy, under local anesthesia with intravenous
      sedation in the pulmonary endoscopy suite, are appropriate candidates for this
      procedure. It is absolutely mandatory that physicians intent on performing this
      procedure be adequately trained. We believe that collaboration between thoracic
      surgeons and pulmonologists not only facilitate training in thoracoscopy, but
      also insure that patients undergoing thoracoscopy will be carefully assessed from
      both perspectives.

PMID- 8521704
TI  - Thoracoscopy in the diagnosis and treatment of spontaneous pneumothorax.
AB  - Thoracoscopy is a highly effective procedure for treating spontaneous
      pneumothorax. This article describes the lesions of pneumothorax and reviews four
      stages of spontaneous pneumothorax, as well as treatment by thoracoscopy.

PMID- 8521705
TI  - Thoracoscopic management of malignant pleural effusions.
AB  - Thoracoscopy has been around for decades, advocated by some, but until recently,
      ignored by many. Not surprisingly, its diagnostic and therapeutic efficacy in
      patients with suspected or proven malignant pleural effusions has withstood the
      test of time. Today, the potential benefits of thoracoscopy must be weighed
      against its cost in patients with limited life expectancy. Although diagnostic
      thoracoscopy requires only overnight hospitalization, pleurodesis imposes a
      longer hospital stay. The discomfort of an indwelling chest tube, the need for
      hospitalization, and the financial burden of thoracoscopic procedures compared
      with less-invasive means of pleural investigation and pleurodesis must be taken
      into account on an individual basis. Thoracoscopy should not be performed for the
      sake of intervention. Its indications and all diagnostic or therapeutic
      alternatives should always be carefully examined. Its role, however, in the
      diagnosis and treatment of patients with malignant pleural effusions is
      undeniable. The diagnostic accuracy of thoracoscopic pleural biopsy is excellent.
      Several studies demonstrate that thoracoscopic talc pleurodesis is more
      frequently successful than other methods of pleurodesis. As a staging procedure,
      thoracoscopy helps determine extent of disease, and possibly, prognosis in
      patients with metastatic pleural carcinomatosis, lung cancer, and malignant
      mesothelioma. As this procedure is increasingly rediscovered by our medical and
      surgical communities, greater clinical and experimental investigation aimed at
      establishing successful management strategies in patients with malignant pleural
      effusions will hopefully occur.

PMID- 8521706
TI  - The value of ultrasound-guided fiberoptic bronchoscopy.
AB  - Flexible fiberoptic bronchoscopy is the procedure of choice for the diagnosis of
      endobronchial neoplasm. Because of technical limitations of fiberoptic
      bronchoscopy, the use of ultrasound assistance was initiated and evaluated. This
      article reviews the technique, study design, and clinical results of ultrasound
      assisted fiberoptic bronchoscopy.

PMID- 8521707
TI  - Transbronchial needle aspiration and percutaneous needle aspiration for staging
      and diagnosis of lung cancer.
AB  - In summary, knowledge of the exact location of lymph nodes in mediastinum and
      hilar areas and their relationship to the puncture site of TBNA is the first step
      to a successful TBNA. The necessity to determine the N3 status and multistation
      status of patients with bronchogenic carcinoma being evaluated for surgery and
      the current financial restraint of the medical care system further highlight the
      potential of this simple, effective, and safe procedure. TBNA can markedly
      enhance the diagnostic yield of flexible bronchoscopy. TBNA and PCNA are
      complimentary procedures.

PMID- 8521708
TI  - Reproductive health: a rendezvous with human dignity.

PMID- 8521709
TI  - Enlarged follicles in women using oral contraceptives.
AB  - Ultrasound examination of the ovaries was performed in the first and/or second
      half of three consecutive cycles in 3 groups of women; Group T who had been using
      a levonorgestrel triphasic oral contraceptive for at least 6 months, Group P who
      had been using a progestogen-only pill for at least 6 months, and Group C, a
      control group. Any follicles greater than 10 mm in diameter and any cysts were
      measured. Fifty-three scans were performed in Group T, 45 in Group P and 31 in
      Group C. Only 4 follicles were detected in 17 women in Group T compared to 10
      follicles in 15 women in Group P and 7 follicles in the women in Group C; all
      follicles were 25 mm or less in diameter except for 3 follicles in 2 women. The
      differences between the groups were not statistically significant. Four enlarged
      follicles were detected in 3 women during 53 scans in Group T, 15 in 8 women (45
      scans) in Group P, and only 1 in 31 scans in Group C. Based upon the proportions
      of scans with enlarged follicles, the difference between Groups T and P was
      statistically significant, indicating that the incidence of enlarged follicles
      was lower in women using a combined oral contraceptive than in those using a
      progestogen-only pill. Furthermore, the study shows that any enlarged follicles
      which occurred were transient.

PMID- 8521710
TI  - Clinical performance of the TCu 380A and Lippes Loop IUDs in three developing
      countries.
AB  - The clinical performance of the Copper T 380A (TCu 380A) and the Lippes Loop
      intrauterine devices (IUDs) were evaluated for 12 months in a group of 710 women
      who had one of the two IUDs inserted. Results are from a randomized clinical
      trial conducted at three collaborating research sites located in three developing
      countries. The gross cumulative life-table pregnancy rate of the TCu 380A IUD was
      found to be lower than that of the Lippes Loop IUD at 12 months (0.7 and 2.1 per
      women, respectively). Although this difference was not statistically significant
      (p = 0.25), it is similar to findings from other studies. The 12-month cumulative
      removal rate due to personal reasons was significantly different (1.4 and 0.0,
      respectively, p = 0.05). Statistically significant differences between the two
      study IUDs were not found with regard to IUD expulsion or IUD removal due to
      bleeding/pain, medical reasons, planned pregnancy or investigator's choice. A
      statistically significant difference (p = 0.03) was observed in the number of TCu
      380A IUD users experiencing dysmenorrhea (26.1%) during the 12-month study
      period, compared to Lippes Loop IUD users (18.8%).

PMID- 8521711
TI  - IUD use and the risk of ectopic pregnancy: a meta-analysis of case-control
      studies.
AB  - Because of inconsistent findings among case-control studies on the relationship
      between IUD use and the risk of ectopic pregnancy, a meta-analysis of published
      literature was conducted. From 1977 through 1994, 19 publications regarding 16
      studies of ectopic pregnancy and IUD use were found by MEDLINE and manual search.
      The odds ratio (ORs) of ectopic pregnancy with current and past IUD use in each
      study were pooled. A quality score system was developed to assess each study.
      Funnel plot was used to assess potential publication biases. For current IUD use,
      when cases were compared to pregnant controls, there was an increased risk of
      ectopic pregnancy (pooled OR: 10.63, 95% confidence interval (CI): 7.66-14.74);
      when cases were compared to non-pregnant controls, there was no risk of ectopic
      pregnancy (pooled OR: 1.06, 95% CI: 0.91-1.24). Past IUD use could mildly
      increase the risk of ectopic pregnancy (pooled OR: 1.40, 95% CI: 1.23-1.59).
      Selecting pregnant or non-pregnant women as controls, however, did not affect the
      OR estimates of past IUD use. Current IUD use does not increase the risk of the
      ectopic pregnancy. However, a pregnancy with an IUD in situ is more often an
      ectopic one than a pregnancy with no IUD. Past IUD use could mildly elevate the
      risk of ectopic pregnancy.

PMID- 8521712
TI  - Differential effects on bone density of progestogen-only methods for
      contraception in premenopausal women.
AB  - The question of differential effects on bone density by two different types of
      progestogen-only methods for contraception in premenopausal women was addressed.
      Data from a prospective randomized clinical trial among 22 premenopausal women,
      age 32.6 (range 20-45 years), who were randomly assigned to either of two
      treatments with continuous progestogens for contraception were analyzed; depot
      medroxyprogesterone acetate (DMPA) or continuous levonorgestrel treatment with
      subdermal implants (Norplant), respectively. Forearm bone density (BMDprox)
      increased with 2.94% (p = 0.006) in women who were prescribed levonorgestrel,
      which was in contrast to stable values in those prescribed depot-medroxy
      progesterone acetate; group difference at 6 months for BMDprox 3.4% (95% CI 1.3,
      5.5; p = 0.025) and BMDdist 4.1% (95% CI - 1.3, 9.6; p = 0.077). The changes in
      bone density were consistent with the changes in biochemical indices for bone
      metabolism; DMPA users showed signs of increased bone turnover and users of
      levonorgestrel showed increased bone formation with increased levels of both
      alkaline phosphatase (p = 0.004) and osteocalcin (p = 0.007). The findings
      suggest an increase in bone density during treatment with levonorgestrel and
      stable values during short-term administration of DMPA, in standard clinical
      doses for contraception.

PMID- 8521713
TI  - Acceptability of medical abortion with methotrexate and misoprostol.
AB  - A clinical trial of efficacy of methotrexate and misoprostol for abortion was
      performed involving 86 women requesting an abortion at < 56 days gestation. An
      acceptability evaluation was included in the design of the trial. Subjects were
      questioned before the study about their reasons for choosing a medical abortion
      and past experience with surgical abortion. After the study was completed, the
      women were questioned about their medical abortion experience. All questions were
      asked in an open-ended manner. Eighty-five of 86 (99%) patients completed both
      questionnaires. The most common reason cited as to why women chose to have a
      medical abortion was to avoid some aspect of the surgery (48%). Forty-one (48%)
      women had experienced a surgical abortion; 49% of these women chose to have a
      medical abortion because of a "bad" past experience related to the surgical
      procedure. Upon completion of this study, 67 (79%) patients stated the medical
      abortion was a good experience, 12(14%) a bad experience, and 6 (7%) had a
      neutral response. When asked what method they would choose if they were to have
      another abortion, 89% would choose this method of medical abortion rather than a
      surgical abortion. In women who choose to participate in a clinical research
      trail, methotrexate and vaginal misoprostol are an acceptable and desirable
      method of abortion.

PMID- 8521714
TI  - Assessing the acceptability of Norplant contraceptive in four patient
      populations.
AB  - The object of this study was to review the experience of Norplant implants
      insertion at the University of Colorado Health Sciences Center with specific
      attention to the potential impact of source of care and/or clinic site of of
      insertion. Norplant implants were inserted at four different office sites,
      namely, adolescent-teen, resident, certified nurse midwife, and faculty
      physician. The charts of all patients who had Norplant implants inserted between
      April 1991 and September 1992 were reviewed and we attempted to contact each
      patient by telephone to assess clinical course and acceptability of Norplant
      contraceptive. We were able to contact 254 of 414 women (61%) who had Norplant
      implants inserted. The average length of time since Norplant implants insertion
      was 13.2 months. The only significant demographic difference between groups was
      that the adolescent-teen patients were younger, of lower parity, less educated,
      and were more likely to be single than the other three groups. The overall
      removal proportion was 14.6%, and removal proportions were not significantly
      different between any of the four groups. The primary reason for removal was
      unacceptable bleeding (32% of removers). Only 59% of patients returned for follow
      up care. Faculty physician patients were significantly more compliant with follow
      up compared to adolescent-teen and resident patients (p < 0.01). Patient
      retention of Norplant contraceptive is unrelated to age or the clinic setting in
      which the device was inserted. Since similar side effects are experienced by
      retainers and removers, it is unclear what other factors prompt women to seek
      removal. Particularly in the teen and resident groups, follow-up is poor.

PMID- 8521715
TI  - Temporary increase of FSH levels in healthy, nulliparous, young women after
      cessation of low-dose oral contraceptive use.
AB  - The effect of modern low-dose oral contraceptives (OCs) on the levels of follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) in young, health,
      nulligravid women was studied in two independent samples. Elevated FSH levels
      were seen in former OC users compared with never users regardless of menstrual
      cycle phase. The increase in FSH levels seemed to peak one year after cessation
      of OC use. This relationship was still significant after exclusion of women with
      low progesterone levels. LH levels were significantly higher in former users
      compared with never users in the first sample, but not in the second sample. The
      difference in FSH concentrations was very small. Single blood samples were
      obtained from the subjects at each time point even though it is recognized that
      gonadotropin secretion is pulsatile. These results must be regarded as
      preliminary and unconfirmed due to small sample size.

PMID- 8521716
TI  - A morphometric study on the endometrial activity of women before and after one
      year with LNG-IUD in situ.
AB  - The endometrium was studied by morphometry in 34 healthy women before and after
      one year's use of an IUD releasing levonorgestrel at a rate 20 micrograms/24 hr
      (LNG-IUD-20). The effect was compared with that of an IUD releasing 2 micrograms
      levonorgestrel/24 hr (LNG-IUD-2). The appearance of suppressed endometrial
      proliferative activity and increased inflammatory reaction was similar in the two
      experimental groups, suggesting that the morphological alterations were
      independent of the LNG dosage. The result of this study, combined with clinical
      data, suggests that LNG-IUD-20 could replace LNG-IUD-2 without any additional
      side effects. The efficacy of LNG-IUD-20 is also likely to last for a longer
      period than the LNG-IUD-2.

PMID- 8521717
TI  - The effect of levonorgestrel-releasing intrauterine device (20 micrograms/day)
      (LNG-IUD-20) on the morphological structure of human endometrium: a study of the
      endometrial factor VIII activity in the women before and after insertion of LNG
      IUD-20 by the digital image analysis.
AB  - The specimens of endometria were obtained from 18 women using an intrauterine
      device releasing levonorgestrel at 20 micrograms/day (LNG-IUD-20). An
      immunoperoxidase reaction, PAP method, with the antiserum of Factor VIII as the
      primary antibody, was carried out in the endometrial biopsies to detect the
      Factor VIII activity in the endometrial endothelium before and after insertion of
      LNG-IUD-20. The immunoperoxidase activity was quantitatively assessed by a
      computer digital image analyser. The results revealed that there were a lower
      Factor VIII activity in the endometrial endothelial cells after insertion of LNG
      IUD-20 (p < 0.001) when compared with the control. From the results of the
      present study, it is suggested that the synthesis and release of endometrial
      endothelial Factor VIII might be inhibited by the insertion of LNG-IUD20.

PMID- 8521718
TI  - Angelman syndrome.

PMID- 8521719
TI  - Consequence of cryptorchidism: relationship to etiology and treatment.
AB  - Increased risk of infertility and testicular tumors after cryptorchidism is the
      basis for treatment. Over the past few decades the recommended age of therapy has
      become younger and younger, so that currently therapy is recommended before 2
      years of age and as early as 6 months. Evidence indicates that treatment before
      10 years of age reduces the incidence of testicular tumors among men who formerly
      had unilateral cryptorchidism to that of men without a history of cryptorchidism.
      However, the effect of the age of treatment among the bilateral group is unknown.
      Infertility after bilateral cryptorchidism is about six times greater than that
      of the general population, affecting about half of patients; it appears to be
      only two times greater among the unilateral group, affecting about 10% of
      patients. To date no effect of age of therapy has been demonstrated, although
      current studies have not been able to consider the underlying cause of the
      cryptorchidism. Data are not yet available to determine whether pretreatment
      testicular location or size is related to subsequent fertility. The current
      recommendation for treatment within the first 2 years of life is based on the
      progressive degeneration of germ cells within the persistently cryptorchid testis
      after the first year of life. This recommendation should stand, even though some
      testes may be irretrievably damaged before such early therapy, and others may
      suffer minimal or no detrimental effect after delayed treatment. Future
      information may identify specific causes of cryptorchidism and, hence,
      determination of which patients will benefit from early therapy.

PMID- 8521720
TI  - Sixth International Workshop on Human X Chromosome Mapping 1995. Banff, Alberta,
      Canada, June 16-18, 1995. Report and abstracts.

PMID- 8521721
TI  - The gene for the APC-binding protein beta-catenin (CTNNB1) maps to chromosome
      3p22, a region frequently altered in human malignancies.
AB  - beta-Catenin is one of the E-cadherin associated proteins involved in the process
      of cellular adhesion. It has recently been shown to interact with the APC protein
      whose gene is known to be mutated in the germline of familial adenomatous
      polyposis patients. This interaction implies that beta-catenin is a potential
      regulator of the APC gene. The localization of the human beta-catenin gene
      (CTNNB1) to chromosome 3p22, by fluorescent in situ hybridization (FISH), has
      linked the gene to a region that is frequently altered in several human
      malignancies. The location of the gene and the protein interactions suggest the
      importance of beta-catenin in the etiology of various human cancers.

PMID- 8521722
TI  - The EcoRI centromeric satellite DNA of the Sparidae family (Pisces, Perciformes)
      contains a sequence motive common to other vertebrate centromeric satellite DNAs.
AB  - By means of cloning, sequencing, and fluorescence in situ hybridization, we have
      determined that the EcoRI satellite DNA family is conserved in the 10 sparid
      species analyzed here. Its conservation, its chromosomal location at the
      centromere of each chromosome, and its structural features could make this
      satellite DNA family an important structural and/or functional element of the
      centromeres of these species. Monomeric units of this satellite DNA have a
      consensus length of 187 bp. Its sequence is characterized by a high AT content
      and the presence of short runs of consecutive AT base pairs. These monomeric
      EcoRI repeats also contain three to four copies, depending on the species, of a
      short sequence reflecting the repetitive duplication and subsequent divergence of
      an ancestral 9-bp sequence in this family. This sequence motive is conserved in
      some parts of the monomeric units of the different species studied at the same
      positions, and, precisely, surrounding the area in which the curvature of the
      monomeric molecule is greatest. The 9-bp sequence motive is similar to other
      direct-repeat sequences of the centromeric satellite DNAs of other vertebrates,
      including those of amphibians and mammals.

PMID- 8521723
TI  - The rat Prm3 gene is an intronless member of the protamine gene cluster and is
      expressed in haploid male germ cells.
AB  - We have cloned and sequenced the cDNA of a novel gene from the rat protamine gene
      cluster. This gene, preliminarily referred to as Prm3, is intronless and resides
      between the genes for protamine 2 and transition protein 2. Prm3 is transcribed
      from the same strand as these genes and is expressed in haploid stages of
      spermatogenesis. The 410-bp-long cDNA possesses an ORF, coding for a putative 104
      amino acid polypeptide with a high content of glutamic acid.

PMID- 8521724
TI  - Evidence for an unusual ZW/ZW'/ZZ sex-chromosome system in Scardinius
      erythrophthalmus (Pisces, Cyprinidae), as detected by cytogenetic and H-Y antigen
      analyses.
AB  - Fifty-seven individuals of the European cyprinid fish species Scardinius
      erythrophthalmus were sexed by gonad histology, and their karyotypes were
      analyzed by Giemsa staining and C-banding. The chromosome number in somatic
      metaphase plates was 2n = 50. Karyotypes of all gonadal male animals were
      identical, consisting of 48 small meta- or submetacentric chromosomes and a pair
      of large metacentric chromosomes (ZZ males). Of the 33 gonadal females, 16 had a
      karyotype similar to the males' (ZW' females) and 17 had a heteromorphic pair of
      chromosomes, including a large metacentric Z chromosome and a small acrocentric W
      chromosome (ZW females). H-Y antigen typing with cells obtained from a variety of
      tissues revealed that the homogametic ZZ males were H-Y negative and the
      heterogametic ZW females were H-Y positive in all tissues tested. In contrast,
      ZW' females showed no expression of the H-Y antigen in somatic cells but were H-Y
      positive in ovarian cells. These results suggest that the ZW/ZW'/ZZ sex
      chromosomes of S. erythrophthalmus represent an unusual system of sex
      determination and that H-Y antigen expression is coupled with the heterogametic
      sex. Whether the ZW' individuals are indeed heterogametic females or actually sex
      reversed ZZ males, in which chromosomal sex determination is overruled by
      external factors, is discussed.

PMID- 8521725
TI  - Absence of geographic chromosomal variation in the roan and sable antelope and
      the cytogenetics of a naturally occurring hybrid.
AB  - The determination of geographic chromosomal variation in rare or endangered
      species, or those of special management concern, is important, since
      geographically defined cytotypes can negatively influence breeding programs
      involving founders drawn from widely divergent localities. We cytogenetically
      analyzed specimens of the roan (Hippotragus equinus) and sable antelope (H.
      niger) collected from widely divergent localities throughout their respective
      ranges. Each species was characterized by a diploid number of 60 and an invariant
      karyotype. In contrast to the absence of intraspecific variation, however, the
      two species differ with respect to centromeric constitutive heterochromatin and
      numbers of nucleolar organizer regions. These cytogenetic landmarks were
      subsequently used to verify an anecdotal account of a naturally occurring roan x
      sable hybrid. The data show that, despite their markedly distinct phenotypes, the
      roan and sable antelope are nonetheless sufficiently similar genetically to
      produce viable offspring. Hybridization, although a rare event between these
      species, is probably partly promoted by behavioral differences which are not
      always sufficient to prevent mating between them.

PMID- 8521726
TI  - Filling the gaps in the porcine linkage map: isolation of microsatellites from
      chromosome 18 using flow sorting and SINE-PCR.
AB  - Flow-sorted chromosome 18 material from the pig (SSC18) was amplified with SINE
      PCR to generate DNA for molecular cloning. An SSC18-enriched library was
      constructed and subsequently screened with a (CA)15 probe to identify polymorphic
      microsatellites. Eleven unique microsatellites were obtained, six of which
      constituted direct extensions of SINE poly(A) tracts. Eight primer pairs
      amplified polymorphic loci in unrelated pigs. The polymorphic markers were typed
      in a Swedish reference pedigree for porcine genome mapping, but only two of them
      (S0177 and S0179) mapped to SSC18. The remaining markers mapped to chromosomes 3,
      4, 7, 9, and 11. Together with two markers from other sources (S0062 and sw787),
      a four-point linkage group on SSC18 could be established.

PMID- 8521727
TI  - Regional assignment of the human 4-hydroxyphenylpyruvate dioxygenase gene (HPD)
      to 12q24-->qter by fluorescence in situ hybridization.
AB  - Using a panel of human-rodent somatic cell hybrids, we have previously mapped the
      gene (HPD, previously called PPD) encoding 4-hydroxyphenylpyruvate dioxygenase to
      the distal half of the long arm of human chromosome 12, region q14-->qter. To
      obtain a genomic probe useful for fluorescence in situ hybridization (FISH)
      analysis we screened a human leukocyte genomic library and isolated a 13.4-kb
      phage clone, which by restriction fragment and sequence analyses was shown to
      contain exons 1-10 of HPD and approximately 2-kb upstream sequences. We now
      report the subregional localization of HPD to 12q24-->qter based on two color
      FISH analysis employing this clone.

PMID- 8521728
TI  - Assignment of the glucose transporter 1 gene (SLC2A1) to swine chromosome 6q34-
      >qter.
AB  - A cosmid clone containing the glucose transporter gene (SLC2A1) was selected from
      a cosmid library of swine genomic fragments by colony hybridization using the
      cDNA of swine glucose transporter as a probe. The genomic fragment thus cloned
      was partially sequenced, and the sequence was compared first with the sequence of
      the cDNA and then with the reported rat genomic sequence. The sequence homology
      and exon/intron structure indicated that the genomic fragment contained at least
      part of SLC2A1. The fragment, together with vector DNA, was then labeled by
      biotin and used as a probe for in situ hybridization on swine chromosome spreads.
      Hybridization was visualized by the FITC-labeled streptavidin/biotinylated anti
      streptavidin system together with the R-band pattern of chromosomes. The
      fluorescence signals revealed that SLC2A1 is localized on swine chromosome 6q34-
      >qter.

PMID- 8521729
TI  - Independent chromosome segregation and absence of interchromosomal effect at
      first meiotic division in male Chinese hamsters heterozygous for two reciprocal
      translocations.
AB  - Chromosome segregation and interchromosomal effects of reciprocal translocation
      at first meiotic division were investigated by chromosome analysis of meiotic
      cells from male Chinese hamsters heterozygous for two reciprocal translocations.
      We used six stocks heterozygous for two different translocations which were
      obtained by crosses between males and females homozygous or heterozygous for a
      different translocation. The frequency of second meiotic (MII) cells from each
      segregational class of one quadrivalent in heterozygotes for two reciprocal
      translocations agreed with that of the same quadrivalent in heterozygotes for the
      single translocation. This indicates that the two quadrivalents in heterozygotes
      for two reciprocal translocations segregate independently. The mean frequency of
      hyperhaploid MII cells from males heterozygous for two reciprocal translocations
      ranged from 7.1 to 15.4%. These cells were mostly derivatives from 3:1
      disjunctions of the quadrivalents. The percentage of cells with extra chromosomes
      in translocation-unrelated groups was calculated at 0.10-0.25%. The frequency did
      not increase significantly as compared with that in karyotypically normal males,
      in which the mean frequency of hyperhaploid MII cells was 0.39%. These findings
      revealed that reciprocal translocations do not have interchromosomal effects on
      meiotic division in male Chinese hamsters.

PMID- 8521730
TI  - Isolation and mapping of the human EIF4A2 gene homologous to the murine protein
      synthesis initiation factor 4A-II gene Eif4a2.
AB  - We report isolation of human cDNA highly homologous to murine Eif4a2, a gene for
      one of the protein-synthesis initiation factors involved in the binding of mRNA
      to the ribosome. This cDNA, which encodes a 407-amino-acid protein, belongs to a
      highly-conserved gene family, the DEAD-box gene family. The human homologue of
      Eif4a2 was expressed in all normal tissues examined, but in variable amounts,
      being highly expressed in skeletal muscle and ovary, and less abundantly in
      liver, kidney, and pancreas. Furthermore, we have localized the human EIF4A2 to
      chromosome 18p11.2 by fluorescent in situ hybridization.

PMID- 8521731
TI  - 33rd Annual American Cytogenetics Conference. San Diego, California, April 1-4,
      1995. Abstracts.

PMID- 8521732
TI  - Comparative serum bactericidal activity against Pseudomonas aeruginosa of six
      antipseudomonal agents.
AB  - Serum levels and serum bactericidal activities of six antipseudomonal agents were
      studied comparatively in 60 patients. Single intravenous doses of gentamicin (1.5
      mg/kg), piperacillin (4 g), ceftazidime (1 g), imipenem (0.5 g), aztreonam (1 g),
      and ciprofloxacin (200 mg) were given over 30 min to 10 patients each, and serum
      samples were obtained 30 min, 1, 2, 3, 4, 6, 8 and 12 h after beginning the
      infusion. Serum bactericidal activity was determined by the broth microdilution
      method against 10 recent isolates of Pseudomonas aeruginosa. Mean peak serum
      levels were as follows: gentamicin 10.4 micrograms/ml, piperacillin 227.5
      micrograms/ml, ceftazidime 43.5 micrograms/ml, imipenem 17.3 micrograms/ml,
      aztreonam 42.3 micrograms/ml, and ciprofloxacin 3.9 micrograms/ml. All agents
      demonstrated effective serum bactericidal activity (geometric mean titer > 1:2)
      at peak serum levels. Ceftazidime was by far the most potent compound with a mean
      titer of 1:46.5, followed by ciprofloxacin (1:17), imipenem (1:13.7), and
      aztreonam (1:13.4). Ceftazidime also showed the longest duration of activity with
      a mean titer of 1:5.1 at 4 h. Based on our results, ceftazidime appeared to be
      the most potent antipseudomonal agent, while gentamicin and piperacillin were the
      least effective.

PMID- 8521733
TI  - Verapamil-tobramycin synergy in Pseudomonas cepacia but not Pseudomonas
      aeruginosa in vitro.
AB  - Virtually all patients with cystic fibrosis (CF) die of respiratory failure
      resulting from chronic progressive pulmonary infections. Pseudomonas aeruginosa
      and Pseudomonas (Burkholderia) cepacia are the two major bacterial pathogens
      responsible for the pulmonary deterioration in these patients. Tobramycin has
      variable inhibitory effects on these organisms, but in many isolates this
      inhibition is increased in vitro by exposure to the diuretic, amiloride.
      Aerosolized amiloride has been shown to be of clinical benefit in CF. The basis
      for this synergy is unknown. To examine the possibility that amiloride-tobramycin
      synergy is mediated through a bacterial efflux mechanism mediated by a multidrug
      resistant (mdr) protein, we studied the inhibitory effect of verapamil, a known
      mdr inhibitor on the tobramycin MIC in P. aeruginosa and P. cepacia using
      standard MIC and synergy testing. Verapamil had no effect on the tobramycin MIC
      in P. aeruginosa but was able to act synergistically with tobramycin in reducing
      the tobramycin MIC markedly in all isolates of P. cepacia tested. This
      combination of drugs may be worth studying as a new treatment strategy for
      resistant P. cepacia infections.

PMID- 8521734
TI  - Comparison of imipenem and five other antipseudomonal agents against gentamicin
      susceptible and -resistant Pseudomonas aeruginosa.
AB  - The in vitro activities of imipenem, aztreonam, piperacillin, ciprofloxacin and
      amikacin were tested by the microbroth dilution technique against 86 clinical
      isolates of Pseudomonas aeruginosa. Imipenem and ciprofloxacin were the most
      active agents against gentamicin-susceptible P. aeruginosa. Only imipenem
      inhibited gentamicin-resistant P. aeruginosa at < or = 8 micrograms/ml. The
      finding that none of the gentamicin-resistant strains were resistant to imipenem
      and amikacin indicated the superiority of these antibiotics to the other agents
      in hospital-associated gentamicin-resistant P. aeruginosa infections.

PMID- 8521735
TI  - In vitro activity of trimethoprim in association with sulfimidazole against
      aerobic gram-negative and gram-positive microorganisms and Clostridia.
AB  - The in vitro activity of a chemotherapeutic agent, sulfimidazole (SIZ), obtained
      by combining two molecules belonging to groups of extremely different
      antibacterial drugs, p-aminobenzene sulfonamide and a derivative with a 5
      nitroimidazole ring, was studied. In association with trimethoprim, SIZ induces
      an intense synergistic antibacterial effect on gram-negative and gram-positive
      aerobic microorganisms and Clostridia. The results show that, in SIZ, the
      activity of each starting molecule remains unchanged providing that its structure
      action relationship is kept intact.

PMID- 8521736
TI  - Piperacillin tazobactam compared with co-amoxiclav, ampicillin plus sulbactam and
      timentin against beta-lactamase-producing clinical isolates of Escherichia coli,
      Klebsiella pneumoniae and Klebsiella oxytoca.
AB  - A total of 266 enterobacterial isolates (Escherichia coli = 190, Klebsiella
      pneumoniae = 49, K. oxytoca = 27) were tested for susceptibility (Bauer-Kirby
      agar disk diffusion test and agar dilution procedure) to ampicillin, ampicillin
      in 10 micrograms/ml of sulbactam, amoxicillin in 4 micrograms/ml of clavulanic
      acid, piperacillin, piperacillin plus tazobactam (8:1 ratio), ticarcillin and
      timentin (ticarcillin in 4 micrograms/ml of clavulanic acid). Discrepant results
      between the two methods of susceptibility testing were categorized as follows:
      category I = very major [minimal inhibitory concentration (MIC) = resistant, disk
      diffusion = susceptible] category II = major (MIC = susceptible, disk diffusion =
      resistant), category III = minor (MIC = intermediate susceptibility, disk
      diffusion = susceptible), category IV = slight (MIC = resistant, disk diffusion =
      intermediate), category V = minimal (MIC = susceptible, disk diffusion =
      intermediate) and category VI = negligible (MIC = intermediate, disk diffusion =
      resistant). The antibiotics, or combinations with beta-lactamase inhibitors,
      yielded the following discrepant results: ampicillin (II = 2, V = 1 and VI = 3),
      co-amoxiclav (I = 5, III = 25, IV = 1 and V = 3), ampicillin plus sulbactam (I =
      5, II = 3, III = 1, V = 19 and VI = 1), piperacillin (II = 15, III = 1, V = 15
      and VI = 85), piperacillin plus tazobactam (III = 16, IV = 2, V = 1 and VI = 5)
      and timentin (I = 2, III = 48 and IV = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521737
TI  - Uptake and intracellular activity of fleroxacin in phagocytic cells.
AB  - The uptake and intracellular activity of fleroxacin in murine J774.1 macrophages
      and human polymorphonuclear leukocytes were studied. The uptake of fleroxacin by
      J774.1 macrophages was rapid and reversible. The cellular to extracellular
      concentration ratios of fleroxacin in both types of phagocytes ranged from 5 to
      6. These ratios were almost equal to those of ofloxacin and ciprofloxacin, and
      higher than those of the beta-lactam antibiotics, flomoxef and piperacillin. The
      intracellular activity of fleroxacin in J774.1 macrophages, examined with
      Staphylococcus aurenus as a test bacterium, showed that its bactericidal action
      was dependent on both the extracellular concentration and the exposure time.
      Fleroxacin reduced the number of viable cells of ingested S. aureus at an
      extracellular concentration that simulated the clinical serum levels, that is,
      killing more than 70% of the bacteria at 4 micrograms/ml. The bactericidal
      activity of fleroxacin in phagocytes was superior to that of erythromycin,
      flomoxef and piperacillin. These results indicate that fleroxacin is taken up
      well by phagocytes, reaching a concentration several fold higher than the
      extracellular concentration, and that it has potent activity against
      intracellular pathogens.

PMID- 8521738
TI  - Influence of brodimoprim on polymorphonuclear leukocyte phagocytosis and oxidant
      radical production.
AB  - Antibiotics not only reach the site of infection, but also penetrate cyclically,
      during a treatment, into polymorphonuclear leukocytes (PMNs) and may influence
      their functions positively or negatively. With reference to these aspects, the
      influence of brodimoprim (BMP), a dimethoxybenzylpyrimidine recently entered into
      clinical use, on human PMN phagocytosis and oxidant radical production
      (chemiluminescence) was investigated. PMNs from healthy adult donors were
      incubated for 50 min in medium alone or in medium containing increasing
      concentrations (3.7, 7.5, 15, and 30 micrograms/ml) of BMP and trimethoprim
      (TMP). In unwashed PMNs, phagocytosis was not modified by BMP, but was
      significantly reduced by 30 micrograms/ml TMP; chemiluminescence was
      significantly reduced by 15 and 30 micrograms/ml BMP and by all concentrations of
      TMP. When PMNs were washed after incubation, phagocytosis was unaffected and
      chemiluminescence was significantly restored. BMP at therapeutic concentrations
      did not influence PMNs and was less toxic than TMP.

PMID- 8521739
TI  - Diltiazem potentiation of doxorubicin cytotoxicity and cellular uptake in Ehrlich
      ascites carcinoma cells.
AB  - The calcium channel blocker diltiazem, which possesses coronary vasodilator
      activity, greatly enhanced the cytotoxicity of doxorubicin in Ehrlich ascites
      carcinoma cells. 20% of the doxorubicin-treated tumor-bearing animals (2 mg/kg,
      every other day, three doses) survived, with a mean survival time of 35 days.
      However, pretreatment with diltiazem increased survival to 70% with a mean
      survival time of 43 days. Diltiazem treatment increased the intracellular level
      of doxorubicin, and there was a good correlation between the high cellular level
      of doxorubicin and its cytotoxic activity. In tumor-bearing animals pretreated
      with diltiazem, doxorubicin showed a pronounced inhibitory effect on cellular
      DNA, RNA content and acid phosphatase activity of tumor cells. In addition, there
      was a marked increase in cellular cholesterol and lipid contents. This study may
      suggest the benefit of using diltiazem to potentiate the cytotoxic effect of
      doxorubicin, allowing its dose and consequently the serious side effects to be
      reduced.

PMID- 8521740
TI  - Endogenous production of tumor necrosis factor alpha in combination with
      hyperthermia for the treatment of mice bearing Ehrlich ascites tumor.
AB  - Multiple hyperthermia was found to exert an additive antitumor effect when
      combined with the in vivo production of tumor necrosis factor alpha (TNF-alpha)
      in mice bearing Ehrlich ascites tumor (EAT). TNF-alpha was produced in EAT
      bearing mice by priming the animals with zymosan and subsequently challenging
      with lipopolysaccharide (LPS). Mice were pretreated with sulindac and D
      mannoheptulose to alleviate the toxic side effects of LPS. While the ability of
      these tumor-bearing mice to produce TNF-alpha remained unchanged under
      hyperthermia, the EAT cell number was suppressed in the combined-treatment group
      compared with groups treated with TNF-alpha or hyperthermia alone. In the same
      comparison, the life span of EAT-bearing mice in the combined-treatment group was
      prolonged.

PMID- 8521741
TI  - Ribonucleotide reductase: an important enzyme in the replication of herpes
      simplex virus type 1 and a target for antiviral chemotherapy.
AB  - Herpes simplex virus encodes a ribonucleotide reductase that catalyzes the
      formation of deoxyribonucleotides from ribonucleotides. The enzyme is not
      essential for either viral DNA synthesis or replication, yet inhibitors of this
      enzyme suppress viral replication. To clarify the role of the ribonucleotide
      reductase in virus infection and to evaluate it as an antiviral target, the
      metabolism of deoxyribonucleotides in infected cells was examined. Our results
      show that the cellular ribonucleotide reductase is incapable of generating
      adequate deoxyribonucleoside triphosphate pools to support efficient virus
      replication. Additionally, we have shown that the virus is unable to efficiently
      utilize salvaged deoxyribonucleosides from degraded cellular DNA. A selective
      inhibitor of the viral ribonucleotide reductase, 2-acetylpyridine
      thiosemicarbazone, decreased deoxyribonucleotide pools in infected cells, thus
      inhibiting viral DNA synthesis. This compound also inhibited the cellular
      ribonucleotide reductase to some extent, thereby enhancing its antiviral
      activity. The antiviral effects of acyclovir were potentiated by 2-acetylpyridine
      thiosemicarbazone in the wild-type virus but not in the ribonucleotide reductase
      mutant, ICP6 delta. Collectively, these data strongly suggest that the viral
      ribonucleotide reductase is an important enzyme in viral replication and a valid
      target for antiviral chemotherapy.

PMID- 8521742
TI  - Malaria therapy and prophylaxis with cotrifazid, a multiple complex combination
      consisting of rifampicin + isoniazid + sulfamethoxazole + trimethoprim.
AB  - This report contains the first therapeutic results with the multiple combination
      rifampicin + isoniazid + sulfamethoxazole + trimethoprim in the treatment of
      malaria. Clinical symptoms declined rapidly and parasites were cleared from the
      erythrocytes. Tolerance was excellent. This fixed combination is outstandingly
      practicable, with few problems with compliance.

PMID- 8521743
TI  - Teicoplanin in endocarditis: a multicentre, open European study.
AB  - The efficacy of teicoplanin, a glycopeptide antibiotic, in endocarditis is
      controversial, with differences observed in the efficacies of the regimens used
      in clinical trials in the USA and Europe. This retrospective study examined the
      outcomes, efficacy and safety of mono- and combination antibiotic therapy using
      teicoplanin, particularly in cases of Staphylococcus aureus endocarditis. A total
      of 115 patients, typically mixed endocarditis patients intolerant of previous
      antibiotic treatment, was enrolled at 29 centres throughout Europe. Combination
      therapy was more successful than monotherapy for treating native valve
      endocarditis (NVE) (93 vs. 85%, p > 0.05, NS) and for treating S. aureus NVE (84
      vs. 50%, p > 0.05). Efficacies for prosthetic valve endocarditis (PVE) were
      similar (75 vs. 79%), while combination therapy was more successful in S. aureus
      PVE (100 vs. 67%) though the number of such patients was small (NS). Adverse
      events were reported by 24% of patients, with 19% probably or possibly related to
      teicoplanin. In 9% of cases the adverse event led to the termination of therapy.
      Teicoplanin was judged to be efficacious in mono- or combination therapy in
      streptococcal endocarditis, though augmentation with an aminoglycoside is
      recommended. The efficacy of teicoplanin demonstrated in enterococcal
      endocarditis represents a major therapeutic advance.

PMID- 8521744
TI  - A comparative study between teicoplanin alone and flucloxacillin, plus or minus
      fusidic acid, in the treatment of serious infections caused by methicillin
      susceptible gram-positive bacteria.
AB  - A randomized trial compared teicoplanin alone against flucloxacillin, with or
      without fusidic acid, in the treatment of serious gram-positive infections. The
      majority of infections involved Staphylococcus aureus or Staphylococcus
      epidermidis, methicillin-resistant organisms were excluded. A total of 56
      patients were evaluable for efficacy, with no significant differences between
      treatment groups. Clinical success (cure + improvement) was achieved in 24/27
      patients on teicoplanin (89%), 16 on flucloxacillin (100%) and 8/9 receiving
      flucloxacillin/fusidic acid (89%). Adverse events occurred in 21% of patients (7
      on teicoplanin and 6 receiving flucloxacillin +/- fusidic acid). All such events
      resolved spontaneously or following appropriate management. It is concluded that
      teicoplanin monotherapy, 400 mg once daily, shows similar efficacy and
      tolerability to multiple daily doses of flucloxacillin, with or without fusidic
      acid, in the treatment of methicillin-susceptible serious gram-positive
      infection.

PMID- 8521745
TI  - Artificial immunization of rabbits with Hyalomma dromedarii tick-derived midgut
      antigen.
AB  - New Zealand white rabbits were immunized with partly fed Hyalomma dromedarii tick
      derived midgut concealed antigens (supernate and pellet fractions) and Freund's
      complete adjuvant (FCA). The rabbits received three inoculations subcutaneously
      on days 0, 14 and 21 at a dose rate of 1 mg antigen per animal. The effects of
      the immunity induced was determined by infesting the rabbits with adult H.
      dromedarii ticks. In immunized rabbits a significant reduction in tick yield,
      engorgement weight, oviposition period, egg mass weight and percentage of egg
      hatchability was found. The gut supernatant antigen fraction induced the best
      protection in terms of reduced feeding and reproductive performance of the ticks.

PMID- 8521746
TI  - Changing patterns of vitellin-related peptides during development of the cattle
      tick Boophilus microplus.
AB  - The major components of protein extracts from the cattle tick Boophilus microplus
      eggs and larvae of various ages were characterized by molecular sieving
      chromatography, ion exchange chromatography and SDS-PAGE. The fractions analysed
      showed a changing chromatographic pattern development. A serum raised against the
      components of a fraction showing characteristics of vitellin strongly reacted in
      Western blots with the major peptides of extracts from eggs, larvae, gut and
      ovary. Comparison of patterns obtained by electrophoresis in non-denaturing PAGE,
      stained with Coomassie blue or with benzidine/hydrogen peroxide, revealed that
      the major proteins of these extracts are haemoproteins, possibly in different
      aggregation states or heterogeneous in composition.

PMID- 8521747
TI  - A modified technique for extracting live ticks from small soil and litter
      samples.

PMID- 8521748
TI  - Clinical importance of hepatic cytochrome P450 in drug metabolism.

PMID- 8521749
TI  - Xenobiotic metabolism in brain.

PMID- 8521750
TI  - Phenytoin disposition and toxicity: role of pharmacogenetic and interethnic
      factors.

PMID- 8521751
TI  - The effects of hypoxia on drug-metabolizing enzymes.

PMID- 8521752
TI  - The mechanism of microsomal azoreduction: predictions based on electronic aspects
      of structure-activity relationships.
AB  - The mechanism of microsomal azoreductase is regulated by the overall Hammett
      sigma substituent values on each ring. A substrate dye must exhibit an overall
      Hammett sigma substituent value either equal or more negative than -0.37 on
      either ring. Dyes with Hammett sigma substituent constants less negative than 
      0.37 will not be reduced by microsomal cytochrome P450. Microsomal reduction of
      azo dyes containing only electron-donating substituents on either ring is
      insensitive to both oxygen and carbon monoxide. The required Hammett sigma
      substituent value on the opposite benzene (prime) ring for I-substrates is
      therefore, sigma' P < or = 0. Reduction of azo dyes containing electron
      withdrawing group on opposite (prime) is sensitive to both oxygen and carbon
      monoxide. The required Hammett sigma substituent value on the opposite benzene
      (prime) ring for S-substrates is, consequently, sigma' P > 0 (Table 3). Redox
      Potentials. Anaerobic cyclic voltammograms of azobenzene derivatives verify the
      following points: A nonsubstrate azo dye will not exhibit a positive potential.
      (Several nonsubstrate hydrazobenzenes exhibited positive potentials, but in a low
      range 0.41-0.48 V. Consequently, cyclic voltammetry can distinguish between
      nonsubstrate azobenzenes and their nonsubstrate half-reduced hydrazo analogs.) A
      substrate azo dye will exhibit a positive potential in the range +1.00 to +1.50
      V. I-substrate: Both negative potentials are stable in air. S-substrate: The
      first negative potential will immediately quench upon exposure to air. I
      substrates exhibit on average potentials which are approximately 0.6 V more
      negative than those for S-substrates. A comparison between the oxidative and the
      reductive pathway of microsomal cytochrome P450 indicates a similarity in the
      first two steps in the reaction cycle, for example, substrate binding and uptake
      of the first electron by the cytochrome [76, 109, 110]. Upon reduction of the
      iron, ferrous cytochrome P450 may bind oxygen or carbon monoxide in a competitive
      manner in the oxidative cycle or may directly transfer the electrons to the
      substrate in a stepwise fashion in the reductive cycle [76]. Estabrook et al.
      [111] suggested that carbon monoxide insensitivity can occur when the formation
      of ferrous cytochrome P450 substrate complex is rate limiting for the overall
      reaction. Structure-activity relationships of azo compounds depend on (1) the
      electron transport component and (2) the oxidation-reduction potential of the
      dye, which determines its ability to accept electrons from cytochrome P-450.
      Nesnow et al. examined a group of 36 aryl azo dyes for their ability to be
      reduced by rat liver microsomal azoreductase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8521753
TI  - Reye's and Reye-like syndromes, drug-related diseases? (causative agents,
      etiology, pathogenesis, and therapeutic approaches).
AB  - In the literature the separation between RS and RLS is confusing and makes it
      difficult to plan an appropriate preventive action or to develop new therapeutic
      approaches. We suggest that the generalized damage and encephalopathy seen in
      both RS and RLS may be due to a wide variety of causative agents that contribute
      to a common derangement, principally involving mitochondrial oxidative pathway.
      Fasting status and infections increase the catabolism and the subsequent flux of
      metabolites from peripheral tissues to the liver (FA and amino acids); cytokines
      (TNF, IL-1, and IL-6), in particular, mediate this effect during infection and
      experimental endotoxemia. Some drugs and other toxic compounds induce functional
      and morphological liver mitochondrial derangement. Oxidative metabolism is
      impaired, with subsequent stimulation of alternative pathways of oxidation,
      following production of unusual toxic acyl CoAs and dicarboxylic acids. Toxic
      compounds accumulate in the liver, deranging its functions and causing energy
      depletion, and are also released in the circulation from which they reach other
      tissues, including the brain. Neurons and astrocytes in the brain may be affected
      differently: Neurons suffer from the lack of energy and the effect of toxic
      compounds arriving from the bloodstream, and astrocytes may be directly affected
      by the beta-oxidation derangement. Very important may be genetic predisposition,
      which, by making the patient more sensitive to a particular causative agent, may
      facilitate the onset of RS and RLS. The therapeutic approach is, presently,
      mainly symptomatic, directed as it is to counteracting each alteration shown,
      depending by the clinical gravity. Other pharmacological approaches are only
      studied experimentally, like carnitine supplementation and PGE2 administration,
      or theoretically envisaged, like monoclonal antibody therapy directed at LPS or
      at pro-inflammatory cytokines or treatment with interferon-alpha.

PMID- 8521754
TI  - Is clonidine an effective smoking cessation therapy?

PMID- 8521755
TI  - Therapeutic options in ocular allergic disease.
AB  - The term ocular allergy encompasses a group of diseases in which there is a high
      frequency of atopy, ocular itching, stringy discharge and a papillary
      conjunctival reaction. Conditions confined to the lids and conjunctiva (e.g.
      seasonal allergic conjunctivitis) have a good prognosis but those involving the
      cornea may result in visual impairment (e.g. atopic keratoconjunctivitis). Mast
      cell and eosinophil mechanisms are important in al the ocular allergies, but T
      cell inflammation is prominent only in vernal keratoconjunctivitis, atopic
      keratoconjunctivitis and giant papillary conjunctivitis. Therapy involves the use
      of antigen avoidance (where possible), nonspecific medical therapy (e.g. cold
      compresses, artificial tears), specific medical therapy and, in certain
      situations, immunotherapy and surgery. Topical antihistamines (often in
      combination with a vasoconstrictor) and oral antihistamines are widely used in
      perennial and seasonal conjunctivitis. Levocabastine is a new preparation which
      is more rapid and potent. Mast cell inhibitors [e.g. sodium cromoglycate
      (cromolyn sodium)] have a proven track record as safe and effective therapy for
      all ocular allergic diseases and the newer, more potent nedocromil and lodoxamide
      are now available. Topical steroids are only indicated in sight-threatening
      disease due to their serious adverse effects and other therapy should be
      continued to minimise the dose required. There is a lack of intermediate potency
      and high potency but safe topical preparations. A number of future possibilities
      exist, some of which have been partially explored. Cyclo-oxygenase inhibitors
      have proved of limited use, but inhibitors of lipoxygenase and kinin pathways are
      awaited. Although results with HEPP have been disappointing, other modulators of
      mast cell function (e.g. picumast, beta-agonists and phosphodiesterase
      inhibitors) may prove useful in the future. So far, results with topical
      cyclosporin in serious disease are very encouraging. Future developments in the
      manipulation of eosinophilic products, cytokines and adhesion molecules may also
      be relevant. However, the current situation for those with serious ocular allergy
      remains a disturbing dependence upon topical steroids, with all the attendant
      risks.

PMID- 8521757
TI  - Practical recommendations and new therapies for Wilson's disease.
AB  - Wilson's disease is an inherited disorder of copper accumulation. The basic
      defect is a failure of excretion of excess copper in the bile by the liver for
      loss in the stool. The accumulating copper causes damage primarily to the liver
      and the brain. Patients typically present in the second to the fourth decades of
      life with liver disease, a neurological disease of the movement disorder type, or
      a wide array of behavioural disturbances. Because the manifestations of Wilson's
      disease are so protean, and the disease masquerades so well as something else,
      recognition of the possibility of Wilson's disease is a major problem, leading to
      serious underdiagnosis of the disease. Excellent therapies exist for both the
      prophylaxis and treatment of Wilson's disease. The longer recognition and
      diagnosis are delayed, the greater the risk of permanent damage to liver and/or
      brain. The availability of effective therapy and the risks in delay or therapy
      make the earliest possible diagnosis critical. Once the disease comes under
      consideration, a series of diagnostic steps can be undertaken which almost always
      establish or rule out the diagnosis of Wilson's disease. These include urine
      copper, blood ceruloplasmin, slit lamp examination for Kayser-Fleischer rings,
      and liver biopsy with quantitative copper assay. Currently, there are 4 drugs
      being used as anticopper agents in Wilson's disease. These are zinc, which blocks
      intestinal absorption of copper, penicillamine and trientine, both of which are
      chelators that increase urinary excretion of copper, and tetrathiomolybdate which
      forms a tripartite complex with copper and protein, and can block copper
      absorption from the intestine, or render blood copper non-toxic. Zinc is clearly
      the treatment of choice, in our opinion, for maintenance therapy, for the
      treatment of the presymptomatic patient from the beginning and for the treatment
      of the pregnant patient, because of its complete efficacy and lack of toxicity.
      For the initial treatment of the patient presenting with mild liver failure, we
      empirically use a combination of trientine and zinc. Trientine gives a strong,
      fast, negative copper balance, and zinc induces hepatic metallothionein, which
      sequesters hepatic copper. For the initial treatment of patients presenting with
      neurological disease we use an experimental drug, tetrathiomolybdate, which
      provides rapid, safe control of copper. These latter patients are at great risk
      of serious permanent neurological worsening with penicillamine, and zinc is too
      slow-acting, in our judgment, to be optimal.

PMID- 8521756
TI  - Gender effects in pharmacokinetics and pharmacodynamics.
AB  - There are a number of examples of sex differences in drug pharmacokinetics and
      pharmacodynamics. Recent advances in the characterisation of specific isozymes
      involved in drug metabolism now allow for the preliminary identification of
      enzyme systems that are affected by sex. While current data are somewhat limited
      and not in complete agreement, the majority of studies show that apparent
      cytochrome P450 (CYP) 3A4 activity is higher in women than in men, whereas the
      activity of many other systems involved in drug metabolism may be higher in men
      than in women. Women and men also show different pharmacodynamic responses to a
      variety of drugs. While the clinical significance of these sex differences
      remains to be determined, we anticipate that they will be most important in the
      administration of drugs that have a narrow therapeutic range. In addition, sex
      differences in drug metabolism may be involved in the higher incidence of adverse
      reactions to drugs in women compared with men. Further research is needed to
      determine the scope and significance of these sex differences. Female-specific
      issues such as pregnancy, menopause, oral contraceptive use and menstruation may
      also have profound effects on drug metabolism. These effects can often be
      clinically important. Pregnancy may increase the elimination of antiepileptic
      agents, reducing their efficacy. Oral contraceptive use can interfere with the
      metabolism of many drugs and, conversely, certain drugs can impair contraceptive
      efficacy. More research is needed to determine the impact of menopause, hormone
      replacement and menstruation on drug therapy.

PMID- 8521758
TI  - Guidelines for the use of propafenone in treating supraventricular arrhythmias.
AB  - Propafenone is a sodium channel blocking agent with a mild beta- and calcium
      channel-blocking activity. Several controlled and noncomparative studies have
      documented its efficacy in a variety of supraventricular arrhythmias in both
      adults and children. Propafenone is comparable with other Vaughan-William class I
      antiarrhythmic drugs for acute conversion of atrial fibrillation. It is also
      comparable with other drugs for prevention of recurrences in paroxysmal atrial
      fibrillation and for maintenance of sinus rhythm following successful
      cardioversion of chronic atrial fibrillation. Although propafenone is effective
      in the acute management of junctional reentrant tachycardias, the availability of
      safer drugs precludes its routine use for these arrhythmias. It may, however, be
      preferred for the acute management of haemodynamically well tolerated pre-excited
      atrial fibrillation in patients with the Wolff-Parkinson-White (WPW) syndrome. It
      also has documented efficacy in the long term therapy of patients with junctional
      tachycardias, and is a useful first-line drug in the management of arrhythmias in
      patients with the WPW syndrome, particularly when there is a short anterograde
      refractory period of the accessory pathway. Noncomparative studies were confirmed
      good efficacy and tolerability of propafenone in the short and long term
      management of paediatric supraventricular arrhythmias. It seems to be
      particularly effective for the treatment of ectopic atrial and junctional
      tachycardias, which are generally difficult arrhythmias to manage. Propafenone
      appears to have an acceptable adverse effect profile during both short and long
      term therapy. As with most other antiarrhythmic agents, there is a proarrhythmic
      potential. This has also been observed in children. There is a theoretical
      possibility that the beta-blocking properties of propafenone may protect against
      its proarrhythmic potential. However, this has not been confirmed in clinical
      studies. In conclusion, propafenone appears to be effective in the management of
      a wide spectrum of supraventricular arrhythmias. It should be considered among
      the first line drugs for management of these arrhythmias in patients without
      structural heart disease.

PMID- 8521759
TI  - Prevention of complications in non-insulin-dependent diabetes mellitus (NIDDM).
AB  - It is expected that the number of patients with diabetes mellitus will increase
      in the near future. The high rate of microvascular and macrovascular
      complications developing in these patients will place an even higher burden on
      our healthcare systems. Several pathophysiological factors are involved in the
      development of complications, among which are hyperglycaemia per se, the
      consequent formation of advanced glycation end-products (AGEs) and the
      intracellular accumulation of sorbitol. In addition, hypertension and
      dyslipidaemia also play an important role, especially in the development of
      coronary heart disease and stroke. The major therapeutic goals in patients with
      non-insulin-dependent diabetes mellitus (NIDDM) are to reduce obesity and
      normalise lipid disturbances and increased blood pressure, in order to improve
      the well-being of the patient and reduce the risk of the development of late
      diabetic complications. Often, pharmacological treatment of the hyperglycaemia is
      necessary, in which case sulphonylureas, metformin, alpha-glucosidase inhibitors
      such as acarbose, or insulin may be employed. It is believed that medical
      interventions, by their effect on improving metabolic control, reduce the
      incidence and severity of diabetic complications, especially when considering the
      toxic effects of glucose and the accumulation of AGEs as a consequence of raised
      tissue glucose levels. This concept is also based on extrapolation of the finding
      of the Diabetes Control and Complications Trial that intensive glycaemic control
      in IDDM will prevent the progression of at least the microvascular complications
      like retinopathy and nephropathy. There are, however, no long term studies in
      NIDDM patients to show that treatment with oral antihyperglycaemic agents helps
      to postpone or prevent complications. It is expected that the UK Prospective
      Diabetes Study will show whether better metabolic control, either with oral
      antihyperglycaemics or with insulin, will indeed improve outcome. Several other
      studies aiming at specific risk factor intervention (hypertension,
      hyperlipidaemia, lipid oxidation) in NIDDM patients are currently ongoing.

PMID- 8521760
TI  - Alteplase. A reappraisal of its pharmacology and therapeutic use in vascular
      disorders other than acute myocardial infarction.
AB  - Alteplase is the product of recombinant DNA technology and is chemically
      identical to endogenous tissue-type plasminogen activator: Plasminogen is
      converted to plasmin by alteplase, and fibrinolysis of blood thrombi is
      subsequently stimulated. Alteplase is now firmly established as a treatment of
      choice in the management of acute myocardial infarction. The efficacy of
      intravenous alteplase in the treatment of pulmonary thromboembolism has also been
      established and appears to be similar to that of streptokinase and urokinase in
      this indication and in arterial thrombotic occlusion. However, its use in this
      latter indication and in other vascular disorders has not been as extensively
      documented. Although trials demonstrating the efficacy of intravenous alteplase
      in patients with deep vein thrombosis and intra-arterial alteplase in patients
      with arterial thrombotic occlusion exist, reliable data on the efficacy of the
      fibrinolytic in ischaemic stroke and intracranial haemorrhage are scarce. Little
      clinical benefit is apparent in patients with unstable angina, although careful
      use may be warranted in those with definite pretreatment coronary thrombi. Of
      concern, there is a suggestion that general use of alteplase in patients with
      unstable angina may be associated with increased incidence of myocardial
      infarction. The incidence of major haemorrhage associated with alteplase therapy
      increases with increasing dose and appears to be similar to that seen with other
      fibrinolytic agents. Thus, further well-designed studies of the use of alteplase
      in ischaemic stroke and cerebral haemorrhage are required. However, a small
      subset of patients with unstable angina and definite pretreatment coronary
      thrombi may benefit from alteplase therapy. Further, preliminary data suggest
      efficacy in the therapy of deep vein thrombosis and arterial thrombotic
      occlusion, and alteplase has a proven place in the fibrinolytic treatment of
      pulmonary thromboembolism.

PMID- 8521761
TI  - Deflazacort. A review of its pharmacological properties and therapeutic efficacy.
AB  - Deflazacort is an oxazoline derivative of prednisolone with anti-inflammatory and
      immunosuppressive activity. Both short (4 to 6 weeks) and longer term (13 to 52
      weeks) studies have shown deflazacort to be as effective as prednisone or
      methylprednisolone in patients with rheumatoid arthritis. The drug was at least
      as effective as prednisone in children with juvenile chronic arthritis.
      Insufficient data are available to draw firm conclusions regarding the efficacy
      of deflazacort as treatment for patients with severe asthma, but the drug has
      demonstrated some efficacy as treatment for nephrotic syndrome and other
      applications such as Duchenne dystrophy, systemic lupus erythematosus, uveitis
      and transplantation. The overall incidence of adverse events in deflazacort
      recipients (16.5%) is lower than that recorded in patients treated with
      prednisone (20.5%) or methylprednisolone (32.7%) and similar to that in
      betamethasone recipients (15.3%). Gastrointestinal symptoms are the most
      frequently reported adverse events in deflazacort recipients; other adverse
      events associated with the drug include metabolic and nutritional disorders,
      central and peripheral nervous system disturbances and psychiatric disorders. In
      general, deflazacort appears to have less effect than prednisone on parameters
      which may be associated with the development of corticosteroid-induced
      osteoporosis. Further, the drug appears have less negative impact on growth rate
      in children with diseases requiring corticosteroid therapy. In a study of 2
      months' duration in patients with conditions requiring corticosteroid treatment,
      moderate dosages of deflazacort produced no clinically relevant diabetogenic
      effects. Thus, deflazacort may be associated with less serious metabolic sequelae
      than prednisone but further well designed long term trials are required to
      confirm this. In the meantime, in adults, deflazacort should be reserved for use
      in those pre-disposed to, or who develop, intolerable metabolic sequelae during
      treatment with corticosteroids. In children, however, even though available
      efficacy data are minimal, deflazacort should be considered as an initial option
      in those requiring corticosteroid therapy since the adverse effects caused by
      this drug class are particularly debilitating in this patient group.

PMID- 8521764
TI  - Famciclovir. A review of its pharmacological properties and therapeutic efficacy
      in herpesvirus infections.
AB  - Famciclovir, a synthetic acyclic guanine derivative, is a prodrug which, after
      oral administration, is rapidly metabolised to the highly bioavailable antiviral
      compound penciclovir. Penciclovir is active in vitro against the herpesviruses
      herpes simplex virus (HSV)-1, HSV-2 and varicella zoster virus (VZV). Famciclovir
      is an effective treatment of immunocompetent patients with acute herpes zoster
      (shingles) caused by VZV. Comparative studies have demonstrated that famciclovir
      has therapeutic efficacy similar to that of oral aciclovir (acyclovir) in
      attenuating the acute signs and symptoms of infection (including pain during the
      acute phase of infection). In a placebo-controlled study, famciclovir
      significantly reduced the duration of postherpetic neuralgia; this effect was
      more pronounced (almost a 3-fold reduction) in patients aged > or = 50 years. In
      immunocompetent patients with recurrent genital herpes infection, suppressive
      treatment with oral famciclovir effectively prolonged the time to recurrence of
      symptomatic episodes of infection compared with placebo. In addition, famciclovir
      significantly reduced the duration of viral shedding, accelerated healing of
      genital herpes lesions and reduced the duration of symptoms. Famciclovir is
      reported to be the first antiviral agent to significantly reduce symptoms
      associated with multiple genital herpes lesions. Famciclovir is a well-tolerated
      drug with a tolerability profile similar to that of placebo and aciclovir. Thus,
      famciclovir is now established as an effective treatment of immunocompetent
      patients with herpes zoster or genital herpes infection, particularly as
      famciclovir is administered in a convenient dosage regimen that may improve
      compliance compared with aciclovir.

PMID- 8521763
TI  - Gestodene. A review of its pharmacology, efficacy and tolerability in combined
      contraceptive preparations.
AB  - The newer progestogens gestodene, desogestrel and norgestimate were developed in
      an attempt to produce agents with more selective progestational activity that
      would improve cycle control and minimise metabolic changes and adverse events
      while effectively preventing pregnancy. In clinical practice, gestodene is
      combined with ethinylestradiol in monophasic or triphasic combined oral
      contraceptive preparations. The drug has pharmacokinetic advantages over the
      other new progestogens in that it is active per se (the others are prodrugs) and
      has high bioavailability (approximately 100%). The ability of gestodene
      containing oral contraceptives to inhibit ovulation is similar to that of
      preparations containing other progestogens although the required dosage is lower.
      In common with oral contraceptives containing desogestrel or norgestimate, and in
      contrast with those containing levonorgestrel, gestodene-containing preparations
      are associated with neutral or positive changes in lipid and carbohydrate
      metabolism. The effects of gestodene preparations on coagulation parameters, like
      those of desogestrel and levonorgestrel, are balanced by changes in the
      fibrinolytic system. Although the impact of these changes on clinical
      cardiovascular end-points has not been determined, the altered lipid profile is
      not likely to have significant clinical relevance because of the predominantly
      thrombogenic nature of cardiovascular disease in oral contraceptive users.
      Pregnancy rates and Pearl Indices with gestodene-containing preparations are low
      and similar to those with preparations containing other progestogens. Most
      pregnancies are attributable to user failure. Cycle control appears to be better
      with gestodene preparations than with levonorgestrel preparations, and available
      data suggest that cycle control may also be better with monophasic
      gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate
      containing preparations, and better with triphasic gestodene- than with triphasic
      levonorgestrel- or norgestimate-containing preparations. However, differences
      between the new progestogen-containing preparations need to be confirmed in
      further large-scale trials. The most common adverse events with
      gestodene/ethinylestradiol are headaches and breast tension; the incidence of
      short term adverse events, including acne, is similar to that with preparations
      containing other progestogens. Changes in blood pressure and bodyweight are
      negligible. There are no comparative data on the incidence of cardiovascular
      events with gestodene-containing and other combined preparations. While the risk
      of breast cancer appears to be increased with long term combined oral
      contraceptive use in certain patient subgroups, this risk needs to be balanced
      against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8521762
TI  - Simvastatin. A reappraisal of its pharmacology and therapeutic efficacy in
      hypercholesterolaemia.
AB  - Simvastatin is an HMG-CoA reductase inhibitor used in the treatment of patients
      with hypercholesterolaemia. Since the time simvastatin was previously reviewed in
      Drugs, a number of large clinical trials have confirmed its clinical efficacy.
      Thus, reductions from baseline were approximately 20 to 40% for serum levels of
      total cholesterol, 35 to 45% for low density lipoprotein (LDL)-cholesterol and 10
      to 20% for triglycerides in patients with primary hypercholesterolaemia receiving
      simvastatin 10 to 40 mg/day. High density lipoprotein (HDL)-cholesterol levels
      were increased modestly by about 5 to 15%. Recent data from long term studies
      indicate that little or no attenuation of these changes in serum lipid and
      lipoprotein levels occurred with administration of simvastatin for 3 to 5.4
      years. Comparative studies with other HMG-CoA reductase inhibitors (lovastatin,
      pravastatin and fluvastatin), which were lacking at the time of the previous
      review of simvastatin, demonstrated greater reductions in serum levels of total
      cholesterol and LDL-cholesterol with simvastatin than equal dosages of lovastatin
      or pravastatin. Reductions in serum levels of total cholesterol and LDL
      cholesterol were similar between agents only when lovastatin or pravastatin were
      administered at a total daily dosage twice that of simvastatin and when
      fluvastatin was administered at a total daily dosage approximately 8 times that
      of simvastatin. In general, simvastatin 10 to 40 mg/day was also more effective
      than standard dosages of bile acid sequestrants, fibrates or probucol in lowering
      serum levels of total cholesterol and LDL-cholesterol; however, fibrates usually
      produced greater reductions in serum triglycerides and greater elevations in HDL
      cholesterol levels. The Scandinavian Simvastatin Survival Study (4S), a large
      secondary prevention study in patients with coronary heart disease and
      concomitant hypercholesterolaemia, demonstrated that simvastatin 20 to 40 mg/day
      for a median of 5.4 years significantly reduced overall mortality (the primary
      end-point of the study) by 30% compared with placebo, which was attributed to a
      42% relative reduction in coronary mortality. Coronary morbidity was also
      significantly reduced by simvastatin in the 4S trial. The tolerability profile of
      simvastatin appears to be comparable to that of other HMG-CoA reductase
      inhibitors. The most frequently reported adverse events are gastrointestinal
      disturbances, which are generally mild and tend to occur less frequently than
      with cholestyramine. In conclusion, simvastatin is among the most effective
      agents available for treating patients with hypercholesterolaemia.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8521765
TI  - Recent developments in analgesia during labour.

PMID- 8521766
TI  - Drug utilisation review (DUR) of the third generation cephalosporins. Focus on
      ceftriaxone, ceftazidime and cefotaxime.
AB  - Six parenteral third generation cephalosporins have been introduced into clinical
      use in the past 10 years. The 3 most frequently available agents are cefotaxime,
      ceftriaxone and ceftazidime. These 3 third generation cephalosporins are
      characterised by a broad spectrum of activity and increased stability to beta
      lactamases compared with the first and second generation cephalosporins. However,
      there are growing numbers of reports of resistance to these agents with
      increasing use. The major differences in the properties of the 3 agents are the
      long half-life of ceftriaxone and its dual route of elimination. Ceftazidime is
      best restricted to Pseudomonas aeruginosa infections where other agents are
      contraindicated or ineffective. Cefotaxime and ceftriaxone can be used in
      nosocomial Gram-negative infections where P. aeruginosa can be ruled out. The
      types and incidences of adverse drug reactions are not different for the 3
      agents. A number of drug utilisation review (DUR) studies of these agents in the
      hospital setting have reported a considerable incidence of inappropriate use and
      substantial avoidable costs. There are methodological problems with most of the
      DUR studies, especially the criteria and the methods of cost estimation. The use
      of pharmacoeconomic methodology could ensure more realistic cost estimation;
      however, outcome data are, in most cases, not available.

PMID- 8521768
TI  - Approaches to meeting the criteria for fixed dose antihypertensive combinations.
      Focus on metoprolol.
AB  - Fixed dose antihypertensive combinations are being used increasingly in the
      management of hypertension. There are advantages and disadvantages of this form
      of therapy. The key aims are to: (i) achieve increased efficacy by using drugs
      that complement each other's actions; (ii) use low doses to minimise adverse
      effects; and (iii) provide a simple once daily regimen. Fixed dose combinations
      containing metoprolol have the advantage that beta-blockers are drugs for which
      there is most evidence that they are cardioprotective; metoprolol is the best
      documented beta-blocker in this context. The early combination of conventional
      release metoprolol and hydrochlorothiazide was inadequately investigated by
      modern standards, but proved well tolerated and effective in clinical practice.
      The introduction of the long acting metoprolol CR/ZOK (controlled release/zero
      order kinetics) produced a very satisfactory once daily preparation with no major
      pharmacokinetic interactions. The fixed dose combination of felodipine and
      metoprolol CR/ZOK has been well investigated. The two agents complement each
      other's actions and together provide very effective blood pressure control,
      cardioprotection and very good tolerability. A case can be made that this
      preparation more closely meets the requirements of an ideal antihypertensive than
      a single agent given alone.

PMID- 8521767
TI  - New approaches to the prevention of atherosclerosis.
AB  - In recent years, remarkable progress has been made in the prevention and
      treatment of atherosclerosis. However, much of the research has been devoted to
      the investigation of lipid metabolism and lipid-lowering drugs. This review
      highlights some recent topics in both experimental and clinical investigations,
      with emphasis on studies other than those on lipid-lowering drugs. These topics
      include oxidative modification of lipoproteins, hyperfibrinogenaemia,
      hyperhomocysteinaemia, female sex hormones and endothelium-derived relaxing
      factor (or nitric oxide). Some of these approaches have already been applied in
      the clinic.

PMID- 8521769
TI  - Pharmacological management of erectile dysfunction.
AB  - Pharmacological treatment of erectile dysfunction includes all therapeutic
      modalities based on the use of erectogenic drugs, regardless of the route of
      administration. Intracavernous vasoactive injection therapy is the most commonly
      used treatment for erectile dysfunction. Most patients respond to intracavernous
      injection of either single or multiple vasoactive drugs. Major adverse effects
      related to this treatment include priapism, corporeal pain and the formation of
      nodules or plaques in the corpora cavernosa. Oral administration of drugs aimed
      at improving erectile function has not produced results comparable with those
      obtained with intracavernous injection therapy. However, in patients with
      psychogenic or mild organic impotence, oral treatment with drugs that influence
      either central or peripheral pathways controlling erection may improve erectile
      function. Topical administration of vasoactive drugs in the form of gels, liquid
      solutions or plasters is another attractive alternative for the treatment of
      psychogenic and mild organic erectile dysfunction. Although the ideal drug for
      the treatment of erectile dysfunction has not yet been identified, extensive
      laboratory and clinical research is ongoing and successful results are expected
      in the near future.

PMID- 8521770
TI  - Pharmacological interventions for the induction of ovulation.
AB  - Ovulation induction is the most common medical intervention for the treatment of
      infertility. Clomifene is generally the first treatment choice for patients with
      amenorrhoea, unless there is profound hypothalamic deficiency. When clomifene
      fails to induce ovulation, menotropins (human menopausal gonadotrophin) or
      gonadotrophin-releasing hormone (GnRH) are effective, most notably in WHO group
      1. In this condition associated with low estrogen and gonadotrophin levels, the
      aggregate of reported pregnancy rates is 25% per cycle. In hyperprolactinaemic
      anovulation bromocriptine reduces prolactin levels and thereby restores normal
      cyclicity. In all of the above conditions, the pharmacological agent addresses a
      specific defect in an explicit manner. WHO group 2 ovulatory disorders arise from
      hyperandrogenicity and other conditions that respond less predictably to
      gonadotrophin therapy. In women with WHO group 2 disorders, the aggregate of
      reported pregnancy rates is 8%. Ovulation induction is also used in ovulatory
      infertile women to generate multiple follicles and increase the likelihood of
      fertilisation. The aggregate of pregnancy rates in clomifene trials was 7% per
      cycle, and 6% in gonadotrophin trials. Gonadotrophin therapy is more effective,
      however, in association with assisted reproduction techniques. The contrasting
      treatment success in discrete disorders (25% per cycle) and heterogeneous
      disorders such as WHO group 2 and persistent infertility (6 to 8% per cycle)
      underlines the need for research to discover specific causal mechanisms and
      identify explicit new pharmacological interventions.

PMID- 8521771
TI  - Nifedipine gastrointestinal therapeutic system (GITS). A review of its
      pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in
      hypertension and angina pectoris.
AB  - Nifedipine 'gastrointestinal therapeutic system' (GITS) is a recently developed
      formulation that slowly releases the drug into the intestinal tract over a 24
      hour period. When administered once daily, it is of similar efficacy to sustained
      release formulations of felodipine, verapamil, and diltiazem and at least as
      effective as standard formulations of lisinopril and enalapril, and long-acting
      propranolol and atenolol in the treatment of patients with mild to moderate
      essential hypertension. Substitution of nifedipine GITS for conventional
      formulations of nifedipine, diltiazem or verapamil, maintained adequate control
      of anginal symptoms in patients with stable angina pectoris. Nifedipine GITS
      appears to maintain quality of life and is apparently better tolerated than those
      formulations of nifedipine which require 2 or 3 times daily administration in
      both elderly and younger patients. In addition, it has minimal effect on lipid
      and glucose metabolism and reverses left ventricular hypertrophy, and is thus
      suitable for treatment of the majority of patients with mild to moderate
      hypertension or angina pectoris.

PMID- 8521774
TI  - Acute effects of mercuric chloride on the olfactory epithelium of Trichomycterus
      brasiliensis.
AB  - The olfactory organ in fish has a distinct localization, a major biological
      significance, and an important role in fish behavior. One group of Trichomycterus
      brasiliensis was exposed to two different concentrations of mercuric chloride
      (0.05 and 0.1 mg HgCl2 liter-1). The surface of the olfactory epithelium was
      investigated with scanning electron microscopy. Forty individuals were used in
      this study. The olfactory epithelia were collected after 4, 12, 24, 48, and 96 hr
      from contaminated and control aquaria. In the experiment with 0.1 mg HgCl2 liter
      1 all individuals died within 24 hr with significant damage to the olfactory
      epithelium. Type 1 ciliated cells were the most evidently altered. With 0.05 mg
      HgCl2 liter-1 the initial alterations were considerable, but after 96 hr the
      epithelial surface recovered its initial appearance compared with the control
      individuals. This recovery is due to the resistance of this species and to the
      decrease in the Hg2+ concentration in water. Therefore, the alterations observed
      in this study reveal that inorganic mercury affects the olfactory organs
      structurally, with evident interference with normal behavior.

PMID- 8521775
TI  - Bioextraction of soil boron by tall fescue.
AB  - High concentrations of soil B are detrimental to crop productivity in certain
      arid and semiarid regions of the western United States. Production of tall fescue
      on B-affected soils may be a viable strategy to reduce and maintain soil B
      concentrations at nontoxic levels for most agronomic crops. A 2-year field
      experiment was conducted to study B uptake in tall fescue (Festuca arundinacea)
      Schreb. cv. Au Triumph grown in soil containing potentially toxic levels of
      native soil B. The soil B concentrations (water-extractable B greater than 5 mg B
      liter-1) did not affect the dry matter (DM) yield of tall fescue. Boron
      concentrations in shoot tissue for both years ranged from 88 to 121 mg B kg-1 DM.
      whereas in root tissue, concentrations ranged from 50 to 60 mg B kg-1 DM. For
      both years of the study, soil samples were taken at depth of 0-45 and 45-90 cm at
      the beginning and end of the designated growing season and analyzed for water
      extractable B. Summary data from all cropped plots at the two soil depths
      indicated that the mean water-extractable B concentrations were reduced by 35%
      after 2 years in the tall fescue plots, whereas losses of extractable B from bare
      plots did not exceed 13% for both years. Tall fescue apparently can be used as a
      component in an overall strategy to lower extractable soil native B levels in
      irrigated agriculture soils and potentially reduce leaching of B into shallow
      ground water.

PMID- 8521773
TI  - Amlodipine. A reappraisal of its pharmacological properties and therapeutic use
      in cardiovascular disease.
AB  - Amlodipine belongs to the dihydropyridine class of calcium channel blockers. Both
      short and long term studies indicate that amlodipine effectively lowers mild to
      moderately elevated blood pressure and relieves symptoms of angina pectoris. In
      comparative studies, its antihypertensive efficacy is similar to that of other
      established agents such as beta-blockers, diuretics, ACE inhibitors and other
      calcium channel blockers (including the dihydropyridines); limited comparative
      data are, however, available in patients with angina pectoris. Amlodipine may
      offer potential in patients with congestive heart failure. Vasodilator adverse
      events such as oedema, headaches, and flushing are commonly observed with
      amlodipine. The drug does not appear to cause postural hypotension, reflex
      tachycardia or cardiac conduction disturbances. Comparative studies suggest that
      amlodipine is at least as well tolerated as other standard agents. Thus,
      amlodipine provides an attractive therapeutic option for the treatment of
      hypertension, and offers potential for patients with angina pectoris. Its
      beneficial effects in patients with congestive heart failure require confirmation
      in future studies.

PMID- 8521776
TI  - Toxicity of DTPA to Daphnia carinata as modified by oxygen stress and food
      limitation.
AB  - First-instar Daphnia carinata were exposed to one of four or five sublethal
      concentrations of the industrial chelating agent diethylenetriamine pentaacetic
      acid (DTPA) either alone, or in conjunction with, high (90-100%) or low (10-25%)
      oxygen saturation and high (2 x 10(5) cells/ml) or low (2 x 10(4) cells/ml) food
      conditions for 6 to 7 days, in a series of three experiments. Survival, growth,
      reproduction, and hemoglobin (Hb) content were assessed. Mortality increased
      significantly from 6.5 +/- 4.2 to 38.9 +/- 5.2%, and mean length was
      significantly reduced from 2.73 +/- 0.02 to 1.37 +/- 0.01 mm at 100 mg/liter DTPA
      in experiment 1. Mean length was also significantly reduced from 2.64 +/- 0.12 to
      1.9 +/- 0.1 mm at 50 mg/liter DTPA in experiment 3. This was attributed to an
      indirect effect via the food supply in the third experiment. There was a
      significant decrease in the mean number of first-brood eggs at 10 mg/liter DTPA
      in all three experiments. Hemoglobin concentration was significantly increased
      under low oxygen conditions from 27.6 +/- 1.7 to 65.5 +/- 4.6 mg Hb/g Daphnia dry
      wt, and 23.0 +/- 1.8 to 49.4 +/- 3.5 mg Hb/g Daphnia dry wt in experiments 2 and
      3, respectively. However, DTPA had no effect on hemoglobin concentration in any
      experiment. DTPA toxicity to D. carinata was not significantly altered by oxygen
      stress or food limitation and could not be attributed to an inhibition of Hb
      synthesis. Increased exposure times may result in further reproductive effects
      and also an indirect effect on hemoglobin concentration via the gradual depletion
      of iron stores. The no-observed effect concentration and the lowest observed
      effect concentration for D. carinata in this study were 1.0 and 10 mg/liter DTPA,
      respectively, based on reproduction, giving an estimated threshold concentration
      of 3.2 mg/liter DTPA.

PMID- 8521777
TI  - Toxicology of cupric salts in honeybees. I. Hormesis effects of organic
      derivatives on lethality parameters.
AB  - Feeding bees with organic cupric salts provides long-term control of the parasite
      Varroa jacobsoni. A set of new algebraic parameters (M. Bounias C.R. Acad. Sci.
      310(3), 65-70, 1990) completely describing the population lethality function has
      been calculated following chronic administration of cupric gluconate, aspartate,
      and isoleucinate, with or without dietary pollen. Mortality curves allowed the
      calculation of LT50 (time for 50% lethality) as well as Hill coefficients (h) of
      the curves and the LD50 as a function of time. The tangent at the inflexion point
      of the sigmoidal time/mortality curves (delta i) gave the maximum mortality
      acceleration as an additional parameter. No toxicity (i.e., no decrease of TL50
      vs doses and no LD50 values) was found for cupric gluconate and isoleucinate with
      pollen, whereas increases in LT50 and decreases in delta indicated hormesis
      effects. Doses decreasing by half-time LT50, h, or delta were used as objective
      lethality indexes for comparisons of toxicity in the other cases. Routine acute
      toxicity at high dosage was also compared with phosalone and lindane effects 24
      hr after treatment.

PMID- 8521778
TI  - Bioconcentration of trace metals in rainbow trout: a field study.
AB  - Caged rainbow trout were exposed for a month at two sites in the river Po, one
      upstream and the other downstream of the river Lambro inlet. Gills, spleen,
      kidney, muscle, and vertebral bone were examined for metal content after 7, 15,
      and 30 days of exposure. Cd accumulated mostly in spleen and muscle; Hg in muscle
      and kidney; Pb in bone, spleen, and kidney; Cr in spleen, muscle, and gills; and
      Cu in kidney. The highest Zn levels were measured in gills, but no consistent
      variations were observed. Trends of accumulation, target organs, and estimated
      whole body contents are discussed. Although the metal content of most organs was
      low and variations in concentrations were relatively contained, differences
      between the two stations were observed for Cd, Hg, Pb, and Cr.

PMID- 8521779
TI  - Ready biodegradability test in seawater: a new methodological approach.
AB  - To estimate the persistence of xenobiotic in the environment, a new ultimate
      mineralization approach for assessing ready biodegradability in seawater has been
      developed, based on the OECD 301 B guideline for freshwater. a few changes in the
      currently accepted procedure have been made to adapt the test to seawater. The
      assays, realized with seawater as test medium and inoculum, give high variability
      results of biodegradability. To lower this variability a synthetic marine medium
      joined to a highly concentrated inoculum from a marine aquarium filter have been
      used. The results reveal (i) a decrease of variability, together with an increase
      in degradation rate of the tested chemicals due to a better control of inoculum
      and test medium, and (ii) no difference in easy biodegradable compound (sodium
      benzoate) biodegradation rate when two marine aquarium inocula are tested. This
      study demonstrates that the ready biodegradability test developed on synthetic
      marine medium and inoculum from marine aquarium filter minimizes the effect of
      the sample location on the biodegradation results of compounds and allows
      classifying chemicals as a function of their biodegradability.

PMID- 8521780
TI  - Toxicity of diphenylamine and some of its nitrated and aminated derivatives to
      the luminescent bacterium Vibrio fischeri.
AB  - Aqueous samples containing various nitrated and aminated diphenylamine
      derivatives were subjected to the luminescent bacterium Vibrio fischeri NRRL-B
      11177 to determine their ecotoxicological potential. As the most important
      toxicological parameter, EC50, the concentration needed to reduce bacterial
      luminescence by 50%, was calculated. All compounds tested must be classified to
      the category "very toxic to aquatic organisms" using the widely accepted
      classification scheme of D. Strupp, H.P. Luhr, H. T. Grunder, J. Gerdesmann, and
      J. Ahlers (1990, UWSF--Z. Umweltchem. Okotox. 2, 151-156). Only 2, 4
      diaminodiphenylamine can be classified as "less toxic to aquatic organisms". EC50
      values after 30, 60, and 90 min of incubation of the test compounds are
      presented. For many of the compounds tested in this study there are no
      toxicological data in the literature.

PMID- 8521781
TI  - Pesticide effects on eel metabolism pesticide; levels did not decline at any time
      when animals were exposed to 4.1 mg/liter.
AB  - Previous works on endosulfan eel toxicology in this laboratory demonstrated that
      0.041 mg/liter of endosulfan was the 50% lethal concentration of 96 hr exposure.
      Eels of species Anguilla anguilla were exposed to two sublethal endosulfan
      concentrations: 8.2 micrograms/liter (1/5 LC50) and 4.1 micrograms/liter (1/10
      LC50), and the experiment was done at different exposure times: 12, 24, 48, 72,
      and 96 hr. Muscle glycogen content decreased significantly (p < 0.05) at 24, 48,
      72, and 96 hr exposure to 8.2 micrograms/liter. Muscle lactate levels in fish did
      not change significantly while lactate levels in eel blood increased at 12, 24,
      48, 72, and 96 hr exposure to 8.2 micrograms/liter. Mean blood glucose values
      were elevated after exposure to both endosulfan concentrations. The results are
      discussed in relation to the stress effect produced by the pesticide and the
      related responses of the fish.

PMID- 8521782
TI  - Effect of inducers and PCBs on the cytochrome P450 enzymes in cultured quail
      hepatocytes.
AB  - Hepatocytes isolated from fetal quail livers (Coturnix coturnix japonica) were
      cultured in vitro. Their capacity to metabolize drugs and xenobiotics was
      explored with typical cytochrome P450 substrates: ethoxycoumarin (known to be
      metabolized by several P450s), ethoxyresorufin (essentially dealkylated by
      P450IA1), and testosterone (specifically hydroxylated at several positions by
      several P450s). The cells could be kept metabolically active in culture for at
      least 4 days. Their drug-metabolizing activities were inducible by the usual P450
      inducers, like phenobarbital and benzanthracene, but also by Aroclor 1254, a PCB
      mixture. The results obtained indicate that this experimental model could
      certainly be very helpful in ecotoxicological studies.

PMID- 8521772
TI  - Propofol. An update of its use in anaesthesia and conscious sedation.
AB  - Propofol is an intravenous sedative hypnotic agent which rapidly and reliably
      causes loss of consciousness. It is also associated with a quick and 'smooth'
      recovery, which distinguishes it from many of the more traditional anaesthetic
      regimens. Like other intravenous agents, propofol is both a cardiovascular and a
      respiratory depressant; however, the risk of these effects can be lessened by
      appropriate dosage adjustment or patient management. Anaphylaxis with propofol is
      rare. Propofol anaesthesia in day case surgery is consistently associated with a
      quicker early recovery than other intravenous agents and the more traditional
      anaesthetic regimens. Savings in time to discharge were more variable compared
      with these regimens, although propofol was commonly associated with less post
      operative nausea and vomiting in this period. In the future, the relative
      benefits of propofol compared with the newer volatile agents (desflurane and
      sevoflurane) and propofol/volatile agent combinations need to be examined in this
      clinical setting. There is now clinical experience with propofol in major
      surgical procedures including cardiac and neurosurgery. Propofol has also been
      investigated as a sedative accompanying regional or local anaesthesia for
      diagnostic and therapeutic procedures, and in other clinical settings (ophthalmic
      surgery, cardioversion and electroconvulsive therapy). The unique antiemetic,
      antiepileptic and antipruritic effects of propofol may further broaden its
      appeal. As a result of its favourable recovery profile, propofol holds a central
      place in day case surgery anaesthesia. Accumulating clinical experience in
      cardiac and neurosurgery suggests that the full potential of propofol has yet to
      be realised.

PMID- 8521783
TI  - An aquatic toxicological evaluation of fenthion in the context of finch control
      in South Africa.
AB  - Queletox, containing fenthion as active ingredient, is the avicide formulation
      used in South Africa to control red-billed finches (Quelea quelea). Control
      measures involve night spraying of roosting areas with a light aircraft. Since
      roosting areas often include reedbeds along riversides and on islands, proper
      control is difficult without exposing the aquatic environment to some risk of
      contamination. This study tested the acute effects of fenthion, in association
      with the queletox formulation, on the cladocerans Daphnia pulex and Ceriodaphnia
      dubia and the fish species Poecilia reticulata, Tilapia rendalli, Cyprinus
      carpio, and Oreochromis mossambicus. The chronic effects of fenthion on D. pulex
      were evaluated in a 14-day reproduction test. Mean 48-hr LC50 values estimated
      for D. pulex and C. dubia were 1.30 and 1.72 micrograms liter-1 respectively. For
      the fish estimated 96-hr LC50 values were as follows: 2.12 (P. reticulata), 2.53
      (C. carpio), 2.92 (T. rendalli) and 1.71 micrograms liter-1 (O. mossambicus). In
      the chronic test reproduction of the exposed population was stimulated at the
      lowest two fenthion concentrations (0.1 and 0.6 ng liter-1), while a reproductive
      impairment was recorded at concentrations varying from 1 to 10 ng liter-1.
      Concentrations of fenthion measured in dams after spraying are given to indicate
      the levels of contamination that may occur. QSAR was used to estimate the
      toxicity of some fenthion metabolites. The results of this study reveal that
      fenthion, at the concentrations occurring in the environment after aerial
      spraying, can have marked effects on the survival and reproduction of D. pulex
      for long periods after spraying.

PMID- 8521784
TI  - Cypermethrin-induced in vivo alterations in the carbohydrate metabolism of
      freshwater fish, Labeo rohita.
AB  - Aspects of carbohydrate metabolism under in vivo conditions were analyzed in
      functionally different tissues of the freshwater fish, Labeo rohita, exposed to a
      lethal (LC50/96 hr = 5.24 micrograms liter-1) and sublethal concentration (0.52
      micrograms liter-1) of cypermethrin for 4 days. All exposed fish exhibited a
      hyperglycemic condition. An increase in tissue lactate with a decrease in
      pyruvate, total carbohydrates, and glycogen contents was noted. Activity of
      lactate dehydrogenase was elevated, indicating a shift toward anaerobiosis. TCA
      cycle enzymes, namely succinate dehydrogenase and malate dehydrogenase, were
      inhibited. In most cases changes were more pronounced during a lethal exposure
      compared to sublethal exposure period. The data indicate that the fish has
      adopted a compensatory mechanism to derive energy during pyrethroid toxicosis.

PMID- 8521785
TI  - Uptake and tissue distribution of dietary and aqueous cadmium by carp (Cyprinus
      carpio).
AB  - The aim of this study was to assess whether contaminated prey can be a major
      source of Cd for fish. For this purpose, the uptake and tissue distribution of
      dietary and aqueous cadmium by the carp (Cyprinus carpio) was studied. The fish
      were exposed to either Cd-contaminated food or Cd-contaminated water for 4 weeks
      in laboratory experiments. When exposed to contaminated food, the fish were kept
      in clean water and fed contaminated chironomid larvae, equilibrated with 99
      micrograms Cd. liter-1. During exposure to contaminated water (nominal 100
      micrograms Cd. liter-1; actual 80 micrograms Cd. liter-1) the fish were fed
      uncontaminated food. The Cd accumulation in the tissues of fish fed contaminated
      larvae was, in decreasing order, gut > kidney > liver = gill > muscle. In the
      water experiment this order was gut > gill > kidney > liver > muscle. In almost
      all tissues the Cd uptake was similar for both routes; only the gill had
      accumulated more Cd from Cd-contaminated water than from Cd-contaminated food.
      Considering the ongoing discussion of the importance of Cd transfer from
      contaminated food to predators, these findings suggest that uptake of Cd from Cd
      contaminated prey by fish plays an important role in contaminated waters.

PMID- 8521786
TI  - Microbial bioassays to assess the toxicity of solid-associated contaminants.
AB  - Due to the effects that sediment or soil matrices have on the bioavailability of
      compounds, it has been difficult to screen toxicity of solid-associated
      contaminants. The majority of microbial assays for testing toxicity of soils and
      sediments have been performed on water or solvent extracts. These procedures lead
      to a fractionation of the toxicity, which may underestimate or overestimate
      exposure routes and consequently potential adverse environmental effects.
      Recently, a solid-phase Microtox assay which eliminates the need for soil
      extracts and utilizes whole sediments or soils has been developed. This report
      describes a toxicity testing procedure using the inhibition of dehydrogenase
      enzyme activity of Bacillus cereus as test parameter. Studies with soil samples
      and a synthetic sediment spiked with organic contaminants and copper indicate the
      higher sensitivity of both solid-phase bioassays compared to water extract
      testing. A comparison of the results demonstrates that the B. cereus contact test
      is more sensitive for copper than the Photobacterium phosphoreum solid-phase
      test.

PMID- 8521787
TI  - Mechanisms of nonneoplastic endocrine hyperplasia--a changing concept: a review
      focused on the thyroid gland.
AB  - An important part of clinical endocrinology deals with diseases caused by benign
      and malignant nodules growing within originally homogeneous endocrine glands. In
      the search for the pathogenesis of these nodules, two concepts have been
      advanced: either the hyperplastic tissue is considered to result from chronic
      intense stimulation by a trophic hormone, eventually causing the growth of
      polyclonal nodules (a concept known as NNEH) or else, the nodules are thought to
      represent true clonal tumors. It has been realized rather recently that NNEH
      accounts only for a small minority of rare endocrine diseases, with the exception
      of highly prevalent iodine deficiency goiters and, in a broader sense, for
      Graves' disease. Indeed, secondary hyperplasia of endocrine glands resulting from
      long-lasting chronic hormonal overstimulation cannot explain a large number of
      essential features of the diseased glands. As best documented for the thyroid
      gland, outstanding among the characteristics of hyperplastic glands that do not
      fit into the simple concept of NNEH are the inevitable nodular transformation,
      the frequent autonomy and irreversibility of nodular growth, the loss of function
      in many cells and nodules, and the tremendous regional heterogeneity of growth
      and function including loss of coordination between these two main features of
      any living cell. Hyperplasia resulting from long-lasting stimulation by a trophic
      hormone is not a fully reversible process, as is often thought, but definitely
      increases the total cell mass and leaves behind, after cessation of the stimulus,
      a population of newly generated cells. This process is common to NNEH and true
      neoplastic growth. A review of common and disparate traits between endocrine
      hyperplasia and neoplasia must be based on the following generally accepted facts
      (excluding in-depth consideration of malignancy). 1. Many endocrine tumors are
      clonal while others are polyclonal. For example, pituitary and sporadic
      parathyroid adenomas are nearly always clonal while in the thyroid, multiple
      clonal nodules of different origin may coexist with polyclonal nodules. 2. Clonal
      growth does not necessarily indicate that the autonomous expansion of a tumor is
      driven by presently known genetic gain-of-function or loss-of-inhibition
      mutations or by cytogenetic aberrations. 3. Genetic mutations and chromosomal
      aberration in endocrine tumors are not necessarily primary events in the
      tumorigenesis but may as well be a late secondary phenomenon in growing tissue.
      4. Clonal nodules may overgrow from primarily polyclonal ones. The best evidence
      to date comes from the rare clonal parathyroid adenomas with allelic loss of
      chromosome 11 evolving in tertiary hyperparathyroidism.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8521788
TI  - Molecular biology of somatostatin receptors.

PMID- 8521789
TI  - Thyroid hormone and male gonadal function.

PMID- 8521790
TI  - Incidentally discovered adrenal masses.
AB  - Independently, endocrinology, radiology, and nuclear medicine can not optimally
      differentiate the etiology of the incidental adrenal mass. Rather, the insight
      necessary for this task must be contributed by all three disciplines.
      Incidentally discovered adrenal masses are being detected at an increasing rate.
      This trend is expected to continue based on the incidence of adrenal masses in
      autopsy series and the increasing use of high resolution abdominal imaging
      techniques. CT and MRI are able to definitely characterize only a minority of
      these lesions (simple cyst, myelolipoma, obvious local malignant invasion).
      Biochemical screening for hormone excess is essential regardless of a
      nonsuggestive complete history and physical examination. An argument may be made
      for not further pursuing nonhypersecreting lesions with the typical features of a
      benign adenoma on CT scan and an attenuation value of 0 HU or less.
      Adrenocortical scintigraphy is recommended in all patients with normal
      biochemical screening tests, especially those with CT attenuation values greater
      than 0 HU. In this setting, we believe that the functional and anatomical
      information provided by NP-59 and [75Se]selenomethylnorcholesterol scintigraphy
      allows one to noninvasively, accurately, and less expensively (Table 9)
      categorize adrenal masses as benign nonhypersecretory adenomas (the vast
      majority) vs. a possibly malignant lesion (the minority). In the presence of
      normal biochemistry, a concordant NP-59 imaging pattern is diagnostic of a
      nonhypersecretory benign adrenal adenoma and requires no immediate therapeutic
      intervention. Conversely, patients with discordant patterns of NP-59 scintigraphy
      have lesions that carry a significant risk for malignancy, and the pursuit of a
      tissue diagnosis is indicated, usually by means of FNA. Normal adrenocortical
      tissue on cytological studies in this setting may represent inadvertent sampling
      of adjacent normal adrenocortical tissues or the presence of a well
      differentiated adrenocortical carcinoma. In patients with lesions larger than 2
      cm in whom NP-59 scintigraphy is nonlateralizing, the possibility of a
      periadrenal or pseudoadrenal mass is likely and should prompt review, or perhaps
      even repeat, of high resolution adrenal imaging (occasionally angiography may be
      helpful). In lesions shown to be 2 cm or less in size with a nonlateralizing NP
      59-scan, there is a possibility of a periadrenal or pseudoadrenal mass; however,
      once this is excluded it must be recognized that benign and malignant lesions,
      because of the limitations of scintigraphy, cannot always be clearly
      distinguished by this method when masses are small.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8521791
TI  - Inhibin and activin production in human placenta.

PMID- 8521792
TI  - Prolactin release after mating and genitosensory stimulation in females.
AB  - Study of the mechanisms by which VCS induces the 10-13 days of twice-daily PRL
      surges, while at present incompletely understood, will help us to answer several
      more general neural and endocrine questions: 1) what similarities exist between
      the suckling-induced and VCS-induced changes in pituitary hormone release, and
      what central and peripheral mechanisms might be common to both; 2) how do sensory
      and behavioral factors initiate changes in the pattern of hormone secretion; and
      3) what are the mechanisms underlying the establishment of the short-term and
      long-term mnemonic devices, and do alterations in neural function similar to
      those responsible for other types of memory underlie this memory? As the data
      summarized above demonstrate, a neuroethological approach to the study of these
      questions can be very valuable. The reasons for this are severalfold. First,
      using naturally occurring behavior as an inducer of PSP, it is possible to use
      appropriate controls that allow identification of proximal responses that are
      directly linked to VCS. Females exposed to intromissive stimuli from males show
      responses that are not shown by females receiving the same flank and perineal
      somatosensory input from mounts-without-intromission or the olfactory input from
      nonmating exposure to males. Artificial VCS may induce some nonspecific responses
      that may be more perceived than real. Second, VCS received by the female during
      mating is very different from that applied by mechanical or electrical means, and
      it has been shown that the natural stimuli are important for induction of the PRL
      surges. The fact that intromissions are normally repeated and intermittent has
      revealed that the female responds initially with a graded response to these
      stimuli and that there is a threshold that has to be met for the full response to
      occur. The set-point of this threshold is influenced by factors that are as yet
      unknown. Finally, the natural mating condition reveals the contributions of the
      short-term and long-term mnemonic devices, establishing the existence of a graded
      to all-or-nothing transition that is required for the occurrence of PSP. In each
      of these cases, it is clear that these phenomena are obscured when supramaximal
      artificial stimulation is used as a method to induce PSP. Use of behaviorally
      appropriate stimulation will continue to be a productive way to study this
      system.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8521793
TI  - The metabolic regulation and vesicular transport of GLUT4, the major insulin
      responsive glucose transporter.

PMID- 8521794
TI  - Citation for the 1995 Fred Conrad Koch Award of the Endocrine Society to Jack
      Gorski.

PMID- 8521795
TI  - Citation for the 1995 Edwin B. Astwood Lecture Award to Kenneth S. Korach.

PMID- 8521796
TI  - Citation for the 1995 Rhone-Poulenc-Rorer Clinical Investigator Award to Maria I.
      New.

PMID- 8521797
TI  - Citation for the 1995 Sidney H. Ingbar Distinguished Service Award of the
      Endocrine Society to Jacob Robbins and Joseph Edward Rall.

PMID- 8521798
TI  - Citation of the 1995 Gerald D. Aurbach Lecture Award to Robert Joseph Lefkowitz.

PMID- 8521799
TI  - Citation for the 1995 Robert H. Williams Distinguished Leadership Award of the
      Endocrine Society to David N. Orth.

PMID- 8521800
TI  - Citation for the 1995 Ernst Oppenheimer Memorial Award of the Endocrine Society
      to Deborah L. Segaloff.

PMID- 8521801
TI  - Citation for the 1995 Richard E. Weitzman Memorial Award of the Endocrine Society
      to Mitchell Avery Lazar.

PMID- 8521802
TI  - Electron transport regulates exchange of two forms of photosystem II D1 protein
      in the cyanobacterium Synechococcus.
AB  - Synechococcus sp. PCC 7942 modulates photosynthetic function by transiently
      replacing the constitutive D1 photosystem II protein, D1:1, with an alternate
      form, D1:2, to help counteract photoinhibition under excess light. We show that a
      temperature drop from 37 to 25 degrees C also drives D1:1/D1:2 exchange under
      constant, moderate light. Chilling or light-induced D1 exchange results from
      rapid loss of psbAI message coding for D1:1 and accumulation of psbAII and
      psbAIII messages coding for D1:2. During chilling, a large pool of a novel form,
      D1:2*, transiently accumulates, distinguishable from normal D1 by an increase in
      apparent molecular mass. D1:2* is not phosphorylated and is probably a
      functionally inactive, incompletely processed precursor. After acclimation to 25
      degrees C, D1:2* disappears and D1:1 again predominates, although substantial
      D1:2 remains. Partial inhibition of electron transport under constant, moderate
      light also triggers the D1 exchange process. These treatments all increase
      excitation pressure on photosystem II relative to electron transport. Therefore,
      information from photosynthetic electron transport regulates D1 exchange without
      any requirement for a change in light intensity or quality, possibly via a redox
      sensing mechanism proximal to photosystem II.

PMID- 8521803
TI  - Monitoring dynamic changes in free Ca2+ concentration in the endoplasmic
      reticulum of intact cells.
AB  - Direct monitoring of the free Ca2+ concentration in the lumen of the endoplasmic
      reticulum (ER) is an important but still unsolved experimental problem. We have
      shown that a Ca(2+)-sensitive photoprotein, aequorin, can be addressed to defined
      subcellular compartments by adding the appropriate targeting sequences. By
      engineering a new aequorin chimera with reduced Ca2+ affinity, retained in the ER
      lumen via interaction of its N-terminus with the endogenous resident protein BiP,
      we show here that, after emptying the ER, Ca2+ is rapidly re-accumulated up to
      concentrations of > 100 microM, thus consuming most of the reporter photoprotein.
      An estimate of the steady-state Ca2+ concentration was obtained using Sr2+, a
      well-known Ca2+ surrogate which elicits a significantly slower rate of aequorin
      consumption. Under conditions in which the rate and extent of Sr2+ accumulation
      in the ER closely mimick those of Ca2+, the steady-state mean lumenal Sr2+
      concentration ([Sr2+]er) was approximately 2 mM. Receptor stimulation causes, in
      a few seconds, a 3-fold decrease of the [Sr2+]er, whereas specific inhibition of
      the ER Ca2+ ATPase leads to an approximately 10-fold drop in a few minutes.

PMID- 8521804
TI  - Yeast aminopeptidase I is post-translationally sorted from the cytosol to the
      vacuole by a mechanism mediated by its bipartite N-terminal extension.
AB  - Transport of aminopeptidase I (API) to the vacuole appears to be insensitive to
      blockage of the secretory pathway. Here we show that the N-terminal extension of
      the 61 kDa precursor of API (pAPI) is proteolytically processed in two sequential
      steps. The first step involves proteinase A (PrA) and produces a 55 kDa unstable
      intermediate (iAPI). The second step involves proteinase B (PrB) and converts
      iAPI into the 50 kDa stable, mature enzyme (mAPI). Reversion of the cup1 growth
      phenotype by a pAPI-CUP1 chimera indicates that pAPI is transported to the
      vacuole by a post-translational mechanism. Deletion of the first 16 amino acids
      results in accumulation of the truncated protein in the cytosol, indicating that
      pAPI is actively transported to the vacuole. The chimera pAPI-myc, constructed by
      fusing a myc tag to the C-terminus of pAPI, was exploited to dissect the
      mechanism of pAPI transport. Cell fractionation studies show the presence of iAPI
      myc and mAPI in a fraction of vacuoles purified by density centrifugation. This
      and the sequential conversion of pAPI-myc into iAPI-myc and mAPI lacking the myc
      tag is consistent with insertion of pAPI into the vacuolar membrane through its N
      terminal extension. The specific mechanism of API sorting demonstrates a new
      pathway of protein transport in vacuolar biogenesis.

PMID- 8521805
TI  - A complex of the signal sequence binding protein and the SRP RNA promotes
      translocation of nascent proteins.
AB  - Translocation of proteins across the endoplasmic reticulum membrane is initiated
      by the signal recognition particle (SRP), a cytoplasmic ribonucleoprotein complex
      consisting of a 7S RNA and six polypeptides. To investigate the functions of the
      SRP components, we have tested the activities of several SRP subparticles. We
      show that the SRP GTPase (SRP54) alone binds a signal sequence and discriminates
      it from a non-signal sequence. Although SRP54 alone is unable to promote
      translocation, SRP54 in a complex with SRP RNA is both necessary and sufficient
      to promote translocation of an elongation-arrested nascent protein in a GTP
      regulated manner. For co-translational translocation, additional SRP components
      are required. We discuss the implications of our results for the function of the
      Escherichia coli SRP which is homologous to the SRP54/SRP-RNA complex.

PMID- 8521806
TI  - Early events in preprotein recognition in E. coli: interaction of SRP and trigger
      factor with nascent polypeptides.
AB  - In Escherichia coli, components of a signal recognition particle (SRP) and its
      receptor have been identified which appear to be essential for efficient
      translocation of several proteins. In this study we use cross-linking to
      demonstrate that E. coli SRP interacts with a variety of nascent presecretory
      proteins and integral inner membrane proteins. Evidence is presented that the
      interaction is correlated with the hydrophobicity of the core region of the
      signal sequence and thereby with its ability to promote transport in vivo. A
      second E. coli component, which is identified as trigger factor, can be
      efficiently cross-linked to all tested nascent chains derived from both secreted
      and cytosolic proteins. We propose that SRP and trigger factor act as secretion
      specific and general molecular chaperone respectively, early in protein
      synthesis.

PMID- 8521807
TI  - Non-bilayer lipids are required for efficient protein transport across the plasma
      membrane of Escherichia coli.
AB  - The construction of a mutant Escherichia coli strain which cannot synthesize
      phosphatidylethanolamine provides a tool to study the involvement of non-bilayer
      lipids in membrane function. This strain produces phosphatidylglycerol and
      cardiolipin (CL) as major membrane constituents and requires millimolar
      concentrations of divalent cations for growth. In this strain, the lipid phase
      behaviour is tightly regulated by adjustment of the level of CL which favours a
      nonbilayer organization in the presence of specific divalent cations. We have
      used an in vitro system of inverted membrane vesicles to study the involvement of
      non-bilayer lipids in protein translocation in the secretion pathway. In this
      system, protein translocation is very low in the absence of divalent cations but
      can be enhanced by inclusion of Mg2+, Ca2+ or Sr2+ but not by Ba2+ which is
      unable to sustain growth of the mutant strain and cannot induce a non-bilayer
      phase in E. coli CL dispersions. Alternatively, translocation in cation depleted
      vesicles could be increased by incorporation of the non-bilayer lipid DOPE (18:1)
      but not by DMPE (14:0) or DOPC (18:1), both of which are bilayer lipids under
      physiological conditions. We conclude that non-bilayer lipids are essential for
      efficient protein transport across the plasma membrane of E. coli.

PMID- 8521808
TI  - Influenza hemagglutinin assumes a tilted conformation during membrane fusion as
      determined by attenuated total reflection FTIR spectroscopy.
AB  - Fusion of influenza virus with target membranes is mediated by an acid-induced
      conformational change of the viral fusion protein hemagglutinin (HA) involving an
      extensive reorganization of the alpha-helices. A 'spring-loaded' displacement
      over at least 100 A provides a mechanism for the insertion of the fusion peptide
      into the target membrane, but does not explain how the two membranes are brought
      into fusion contact. Here we examine, by attenuated total reflection Fourier
      transform infrared spectroscopy, the secondary structure and orientation of HA
      reconstituted in planar membranes. At neutral pH, the orientation of the HA
      trimers in planar membranes is approximately perpendicular to the membrane.
      However, at the pH of fusion, the HA trimers are tilted 55-70 degrees from the
      membrane normal in the presence or absence of bound target membranes. In the
      absence of target membranes, the overall secondary structure of HA at the fusion
      pH is similar to that at neutral pH, but approximately 50-60 additional residues
      become alpha-helical upon the conformational change in the presence of bound
      target membranes. These results are discussed in terms of a structural model for
      the fusion intermediate of influenza HA.

PMID- 8521809
TI  - A synthetic peptide corresponding to a conserved heptad repeat domain is a potent
      inhibitor of Sendai virus-cell fusion: an emerging similarity with functional
      domains of other viruses.
AB  - A series of peptides derived from three domains within the fusion protein of
      Sendai virus was synthesized and examined for their potential to inhibit the
      fusion of the virus with human red blood cells. These domains include the 'fusion
      peptide' and two heptad repeats, one adjacent to the fusion peptide (SV-163) and
      the other to the transmembrane domain (SV-473). Of all the peptides tested, only
      SV-473 was highly inhibitive. Using fluorescently-labelled peptides, the
      mechanism through which the SV-473 peptide inhibits the haemolytic activity of
      the virus was investigated. The results suggest that interactions of the active
      peptide with virion elements and lipid membranes are involved. Since it has
      recently been found that synthetic peptides corresponding to putative coiled-coil
      domains of the human immunodeficiency virus (HIV) type 1 transmembrane protein
      gp41 are potent inhibitors of HIV, we discuss the general property of virus
      derived coiled-coil peptides as inhibitors of viral infection.

PMID- 8521810
TI  - C-terminus determinants for Mg2+ and polyamine block of the inward rectifier K+
      channel IRK1.
AB  - Critical loci for ion conduction in inward rectifier K+ channels are only now
      being discovered. The C-terminal region of IRK1 plays a crucial role in Mg2+i
      blockade and single-channel K+ conductance. A negatively charged aspartate in the
      putative second transmembrane domain (position 172) is essential for time
      dependent block by the cytoplasmic polyamines spermine and spermidine. We have
      now localized the C-terminus effect in IRK1 to a single, negatively charged
      residue (E224). Mutation of E224 to G, Q and S drastically reduced rectification.
      Furthermore, the IRK1 E224G mutation decreased block by Mg2+i and spermidine and,
      like the E224Q mutation, caused a dramatic reduction in the apparent single
      channel K+ conductance. The double mutation IRK1 D172N+ E224G was markedly
      insensitive to spermidine block, displaying an affinity similar to ROMK1. The
      results are compatible with a model in which the negatively charged residue at
      position 224, E224, is a major determinant of pore properties in IRK1. By means
      of a specific interaction with the negatively charged residue at position 172,
      D172, E224 contributes to the formation of the binding pocket for Mg2+ and
      polyamines, a characteristic of strong inward rectifiers.

PMID- 8521811
TI  - Mutation of tyrosine-141 inhibits insulin-promoted tyrosine phosphorylation and
      increased responsiveness of the human beta 2-adrenergic receptor.
AB  - The ability of insulin to promote phosphorylation of the human beta 2-adrenergic
      receptor (beta 2AR) was assessed in Chinese hamster fibroblasts transfected with
      beta 2AR cDNA. Phosphotyrosine residues were detected in purified beta 2AR using
      a polyclonal anti-phosphotyrosine antibody and by phosphoamino acid analysis
      following metabolic labelling with inorganic 32P. Treatment of the cells with
      insulin induced a 2.4-fold increase in the phosphotyrosine content of the
      receptor. The insulin-promoted phosphorylation of the beta 2AR was accompanied by
      an increase in the beta-adrenergic-stimulated adenyl cyclase activity.
      Substitution of a phenylalanine residue for tyrosine-141 completely prevented
      both the increased tyrosine phosphorylation and the enhanced responsiveness of
      the beta 2AR promoted by insulin treatment. Mutation of three other tyrosines
      located in the cytoplasmic domain of the receptor, tyrosine-366, tyrosine-350 and
      tyrosine-354, did not abolish the insulin-promoted tyrosine phosphorylation.
      Taken together, these results suggest that insulin promotes phosphorylation of
      the beta 2AR on tyrosine-141 and that such phosphorylation leads to a
      supersensitization of the receptor.

PMID- 8521812
TI  - Critical amino acid residues for ligand binding are clustered in a predicted beta
      turn of the third N-terminal repeat in the integrin alpha 4 and alpha 5 subunits.
AB  - Integrin alpha 4 beta 1 is a receptor for vascular cell adhesion molecule (VCAM)
      1 and fibronectin (CS-1). The alpha 4 beta 1-ligand interaction is involved in
      the pathogenesis of diseases and is, therefore, a therapeutic target. Here, we
      identified critical residues of alpha 4 for ligand binding using alanine-scanning
      mutagenesis of the previously localized putative ligand binding sites (residues
      108-268). Among 43 mutations tested, mutations of Tyr187, Trp188 and Gly190
      significantly inhibited cell adhesion to both VCAM-1 and CS-1. This inhibition
      was not due to any gross structural changes of alpha 4 beta 1. These critical
      residues are clustered in a predicted beta-turn structure (residues 181-190) of
      the third N-terminal repeat in alpha 4. The repeat does not contain divalent
      cation binding motifs. Notably, the mutations within the corresponding region of
      alpha 5 significantly reduced fibronectin-alpha 5 beta 1 interaction. These
      findings suggest that the predicted beta-turn structure could be ubiquitously
      involved in ligand binding of non-I domain integrins.

PMID- 8521813
TI  - Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin
      induced cell proliferation and Stat5 activation.
AB  - While previous studies with truncated erythropoietin receptors (EpRs) have
      suggested that the tyrosine phosphorylation of the EpR does not play a role in Ep
      induced proliferation, we have found, using a more subtle, full length EpR
      mutant, designated Null, in which all eight of the intracellular tyrosines have
      been substituted with phenylalanine residues, that Null cells require
      substantially more Ep than wild-type cells in order to proliferate as
      efficiently. A comparison of Ep-induced proliferation with Ep-induced tyrosine
      phosphorylation patterns, using wild-type and Null EpR-expressing cells, revealed
      that Stat5 tyrosine phosphorylation and activation correlated directly with
      proliferation. Moreover, studies with a Y343F EpR point mutant and various EpR
      deletion mutants revealed that both Ep-induced proliferation and Stat5 activation
      were mediated primarily through Y343, but that other tyrosines within the EpR
      could activate Stat5 in its absence.

PMID- 8521814
TI  - Point mutations within a dimer interface homology domain of c-Mpl induce
      constitutive receptor activity and tumorigenicity.
AB  - c-Mpl, a receptor for thrombopoietin (TPO), belongs to the haemopoietin/cytokine
      receptor superfamily, a group of cell surface molecules characterized by
      conserved sequence motifs within their ligand binding domains. A recurring
      mechanism for the activation of haemopoietin receptors is the formation of
      functional complexes by receptor subunit oligomerization. Within the growth
      hormone receptor, a cluster of extracellular amino acids forms a dimer interface
      domain that stabilizes ligand-induced homodimers. This domain appears to be
      functionally conserved in the erythropoietin (EPO) receptor because substitution
      of cysteines for residues in the analogous region causes EPO-independent receptor
      activation via disulfide-linked homodimerization. This report identifies an
      homologous domain within the c-Mpl receptor. The substitution of cysteine
      residues for specific amino acids in the dimer interface homology regions of c
      Mpl induced constitutive receptor activity. Factor-dependent FDC-P1 and Ba/F3
      cells expressing the active receptor mutants no longer required exogenous factors
      and proliferated autonomously. The results imply that the normal process of TPO
      stimulated Mpl activation occurs through receptor homodimerization and is
      mediated by a conserved haemopoietin receptor dimer interface domain. Moreover,
      cells expressing activated mutant Mpl receptors were tumorigenic in transplanted
      mice. Thus, like v-mpl, its viral counterpart, mutated forms of the cellular mpl
      gene also have oncogenic potential.

PMID- 8521815
TI  - Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing
      signaling complex (DISC) with the receptor.
AB  - APO-1 (Fas/CD95), a member of the tumor necrosis factor receptor superfamily,
      induces apoptosis upon receptor oligomerization. In a search to identify
      intracellular signaling molecules coupling to oligomerized APO-1, several
      cytotoxicity-dependent APO-1-associated proteins (CAP) were immunoprecipitated
      from the apoptosis-sensitive human leukemic T cell line HUT78 and the
      lymphoblastoid B cell line SKW6.4. CAP1-3 (27-29 kDa) and CAP4 (55 kDa),
      instantly detectable after the crosslinking of APO-1, were associated only with
      aggregated (the signaling form of APO-1) and not with monomeric APO-1. CAP1 and
      CAP2 were identified as serine phosphorylated MORT1/FADD. The association of CAP1
      4 with APO-1 was not observed with C-terminally truncated non-signaling APO-1. In
      addition, CAP1 and CAP2 did not associate with an APO-1 cytoplasmic tail carrying
      the lprcg amino acid replacement. Moreover, no APO-1-CAP association was found in
      the APO-1+, anti-APO-1-resistant pre-B cell line Boe. Our data suggest that in
      vivo CAP1-4 are the APO-1 apoptosis-transducing molecules.

PMID- 8521816
TI  - A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and
      protein binding functions.
AB  - Regulation of the cell death program involves physical interactions between
      different members of the Bcl-2 family that either promote or suppress apoptosis.
      The Bcl-2 homolog, Bak, promotes apoptosis and binds anti-apoptotic family
      members including Bcl-2 and Bcl-xL. We have identified a domain in Bak that is
      both necessary and sufficient for cytotoxic activity and binding to Bcl-xL.
      Sequences similar to this domain were identified in Bax and Bip1, two other
      proteins that promote apoptosis and interact with Bcl-xL, and were likewise
      critical for their capacity to kill cells and bind Bcl-xL. Thus, the domain is of
      central importance in mediating the function of multiple cell death-regulatory
      proteins that interact with Bcl-2 family members.

PMID- 8521817
TI  - Newly synthesized protein(s) must associate with p34cdc2 to activate MAP kinase
      and MPF during progesterone-induced maturation of Xenopus oocytes.
AB  - The meiotic maturation of Xenopus oocytes triggered by progesterone requires new
      protein synthesis to activate both maturation-promoting factor (MPF) and mitogen
      activated protein kinase (MAP kinase). Injection of mRNA encoding mutant p34cdc2
      (K33R) that can bind cyclins but lacks protein kinase activity strongly inhibited
      progesterone-induced activation of both MPF and MAP kinase in Xenopus oocytes.
      Similar results were obtained by injection of GST-p34cdc2 K33R protein or by
      injection of a monoclonal antibody (A17) against p34cdc2 that blocks its
      activation by cyclins. Both the dominant-negative p34cdc2 and monoclonal antibody
      A17 blocked the accumulation of p39mos and activation of MAP kinase in response
      to progesterone, as well as blocking the appearance of MPF, although they did not
      inhibit the translation of p39mos mRNA. These results suggest that: (i)
      activation of free p34cdc2 by newly made proteins, probably cyclin(s), is
      normally required for the activation of both MPF and MAP kinase by progesterone
      in Xenopus oocytes; (ii) the activation of translation of cyclin mRNA normally
      precedes, and does not require either MPF or MAP kinase activity; and (iii) de
      novo synthesis and accumulation of p39mos is probably both necessary and
      sufficient for the activation of MAP kinase in response to progesterone.

PMID- 8521818
TI  - In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a
      novel 36 kDa RING finger protein.
AB  - It is proposed that the CDK7-cyclin H complex functions in cell cycle
      progression, basal transcription and DNA repair. Here we report that in vitro
      reconstitution of an active CDK7-cyclin H complex requires stoichiometric amounts
      of a novel 36 kDa assembly factor termed MAT1 (menage a trois 1). Sequencing of
      MAT1 reveals a putative zinc binding motif (a C3HC4 RING finger) in the N
      terminus; however, this domain is not required for ternary complex formation with
      CDK7-cyclin H. MAT1 is associated with nuclear CDK7-cyclin H at all stages of the
      cell cycle in vivo. Ternary complexes of CDK7, cyclin H and MAT1 display kinase
      activity towards substrates mimicking both the T-loop in CDKs and the C-terminal
      domain of RNA polymerase II, regardless of whether they are immunoprecipitated
      from HeLa cells or reconstituted in a reticulocyte lysate. MAT1 constitutes the
      first example of an assembly factor that appears to be essential for the
      formation of an active CDK-cyclin complex.

PMID- 8521819
TI  - The tumour suppressor gene product APC blocks cell cycle progression from G0/G1
      to S phase.
AB  - The APC gene is mutated in familial adenomatous polyposis (FAP) as well as in
      sporadic colorectal tumours. The product of the APC gene is a 300 kDa cytoplasmic
      protein associated with the adherence junction protein catenin. Here we show that
      overexpression of APC blocks serum-induced cell cycle progression from G0/G1 to
      the S phase. Mutant APCs identified in FAP and/or colorectal tumours were less
      inhibitory and partially obstructed the activity of the normal APC. The cell
      cycle blocking activity of APC was alleviated by the overexpression of cyclin
      E/CDK2 or cyclin D1/CDK4. Consistent with this result, kinase activity of CDK2
      was significantly down-regulated in cells overexpressing APC although its
      synthesis remained unchanged, while CDK4 activity was barely affected. These
      results suggest that APC may play a role in the regulation of the cell cycle by
      negatively modulating the activity of cyclin-CDK complexes.

PMID- 8521820
TI  - The higher plant Arabidopsis thaliana encodes a functional CDC48 homologue which
      is highly expressed in dividing and expanding cells.
AB  - We have identified an Arabidopsis thaliana CDC48 gene which, unlike the putative
      mammalian homologue vasolin-containing protein (VCP), functionally complements
      Saccharomyces cerevisiae cdc48 mutants. CDC48 is an essential gene in S.
      cerevisiae and genetic studies suggest a role in spindle pole body separation.
      Biochemical studies link VCP function to membrane trafficking and signal
      transduction. We have described the AtCDC48 expression pattern in a multicellular
      eukaryote; the zones of cell division, expansion and differentiation are
      physically separated in higher plants, thus allowing the analysis of in situ
      expression patterns with respect to the state of cell proliferation. AtCDC48 is
      highly expressed in the proliferating cells of the vegetative shoot, root, floral
      inflorescence and flowers, and in rapidly growing cells. AtCDC48 mRNA and the
      encoded protein are up-regulated in the developing microspores and ovules.
      AtCDC48 expression is down-regulated in most differentiated cell types. AtCDC48p
      was primarily localized to the nucleus and, during cytokinesis, to the
      phragmoplast, a site where membrane vesicles are targeted in the deposition of
      new cell wall materials. This study shows that the essential cell division
      function of CDC48 has been conserved by, at least, some multicellular eukaryotes
      and suggests that in higher plants, CDC48 functions in cell division and growth
      processes.

PMID- 8521821
TI  - Loss of p53 function through PAX-mediated transcriptional repression.
AB  - Direct interactions between the genes that regulate development and those which
      regulate the cell cycle would provide a mechanism by which numerous biological
      events could be better understood. We have identified a direct role for PAX5 in
      the control of p53 transcription. In primary human diffuse astrocytomas, PAX5
      expression inversely correlated with p53 expression. The human p53 gene harbours
      a PAX binding site within its untranslated first exon that is conserved
      throughout evolution. PAX5 and its paralogues PAX2 and PAX8 are capable of
      inhibiting both the p53 promoter and transactivation of a p53-responsive reporter
      in cell culture. Mutation of the identified binding site eliminates PAX protein
      binding in vitro and renders the promoter inactive in cells. These data suggest
      that PAX proteins might regulate p53 expression during development and propose a
      novel alternative mechanism for tumour initiation or progression, by which loss
      of p53 function occurs at the transcriptional level.

PMID- 8521822
TI  - Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c
      myc dependent transformation and are expressed during neural and epidermal
      differentiation.
AB  - The basic helix-loop-helix-leucine zipper (bHLHZip) protein Max associates with
      members of the Myc family, as well as with the related proteins Mad (Mad1) and
      Mxi1. Whereas both Myc:Max and Mad:Max heterodimers bind related E-box sequences,
      Myc:Max activates transcription and promotes proliferation while Mad:Max
      represses transcription and suppresses Myc dependent transformation. Here we
      report the identification and characterization of two novel Mad1- and Mxi1
      related proteins, Mad3 and Mad4. Mad3 and Mad4 interact with both Max and mSin3
      and repress transcription from a promoter containing CACGTG binding sites. Using
      a rat embryo fibroblast transformation assay, we show that both Mad3 and Mad4
      inhibit c-Myc dependent cell transformation. An examination of the expression
      patterns of all mad genes during murine embryogenesis reveals that mad1, mad3 and
      mad4 are expressed primarily in growth-arrested differentiating cells. mxi1 is
      also expressed in differentiating cells, but is co-expressed with either c-myc, N
      myc, or both in proliferating cells of the developing central nervous system and
      the epidermis. In the developing central nervous system and epidermis,
      downregulation of myc genes occurs concomitant with upregulation of mad family
      genes. These expression patterns, together with the demonstrated ability of Mad
      family proteins to interfere with the proliferation promoting activities of Myc,
      suggest that the regulated expression of Myc and Mad family proteins function in
      a concerted fashion to regulate cell growth in differentiating tissues.

PMID- 8521823
TI  - Drosophila Polycomb-group regulated chromatin inhibits the accessibility of a
      trans-activator to its target DNA.
AB  - The genes of the Polycomb-group (Pc-G) are responsible for maintaining the
      inactive expression state of homeotic genes. They act through specific cis
      regulatory DNA elements termed PREs (Pc-G Response Elements). Multimeric
      complexes containing the Pc-G proteins are thought to induce heterochromatin-like
      structures, which stably and heritably inactivate transcription. We have tested
      the functional role of the FAB fragment, a PRE of the bithorax complex. We find
      that this element behaves as an orientation dependent silencer, capable of
      inducing mosaic gene expression on neighboring genes. Transgenic fly lines were
      constructed containing a PRE adjacent to a reporter gene inducible by the yeast
      GAL4 trans-activator. The competition between the activator and Pc-G-containing
      chromatin was visualized on polytene chromosomes using immunocytochemistry. The
      Pc-G protein Polycomb and GAL4 have mutually exclusive binding patterns,
      supporting the notion that Pc-G-induced chromatin structures can prevent
      activators from binding to their target sequences. However, this antagonistic
      function can be overcome by high doses of GAL4, even in the absence of DNA
      replication.

PMID- 8521824
TI  - mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional
      negative regulator with tumor suppressive activity.
AB  - The mammalian mel-18/bmi-1 gene products share an amino acid sequence and a
      secondary structure, including a RING-finger motif, with the Drosophila Polycomb
      group (PcG) gene products Psc and Su(z)2, implying that they represent a gene
      family with related functions. As Drosophila PcG gene products are thought to
      function as transcriptional repressors by modifying chromatin structure, Mel
      18/Bmi-1 might be expected to have similar activities. Here we have analyzed the
      function of mel-18 and found that Mel-18 acts as a transcriptional repressor via
      its target DNA sequence, 5'-GACTNGACT-3'. Interestingly, this binding sequence is
      found within regulatory or non-coding regions of various genes, including the c
      myc, bcl-2 and Hox genes, suggesting diverse functions of mel-18 as the mammalian
      homolog of the PcG gene. We also demonstrate that mel-18 has tumor suppressor
      activity, in contrast to bmi-1, which has been defined as a proto-oncogene.

PMID- 8521825
TI  - A yeast transcription factor bypassing the requirement for SBF and DSC1/MBF in
      budding yeast has homology to bacterial signal transduction proteins.
AB  - The transcription factors SBF and DSC1/MBF bind SCB and MCB promoter elements,
      respectively, and are essential for the cell cycle progression of Saccharomyces
      cerevisiae through the control of G1 cyclin gene expression. We isolated a gene
      (BRY1; Bacterial Response regulator in Yeast) able to activate either MCB or SCB
      promoter elements on a reporter plasmid which, when overexpressed, can bypass the
      normally essential requirement for SBF and DSC1/MBF by the stimulation of CLN1
      and CLN2 expression. In the case of CLN2 at least, this expression depends upon
      the MCB and SCB promoter elements. In wild-type yeast, the disruption of BRY1 has
      no apparent phenotype, but under conditions where the activities of SBF and
      DSC1/MBF are reduced, BRY1 becomes essential. Our data imply the existence of a
      third pathway affecting cyclin expression. BRY1 is the same gene as SKN7 which
      has significant sequence homology to the receiver domains found in response
      regulator proteins from the bacterial two-component signal transduction pathways.
      SKN7 is thought to affect cell wall structure, and when highly overexpressed we
      find that BRY1/SKN7 is lethal perhaps because of perturbations in cell wall
      biosynthesis. The lethality is partially rescued by genes from the protein kinase
      C pathway, but genetic data imply that BRY1/SKN7 and protein kinase C are not in
      the same pathway. Our results suggest that Bry1/Skn7 can influence the expression
      of MCB- and SCB-driven gene expression in budding yeast, perhaps including genes
      involved in cell wall metabolism, via a two-component signal transduction pathway
      which activates Bry1/Skn7 in response to an unidentified signal.

PMID- 8521826
TI  - DNA twist, flexibility and transcription of the osmoregulated proU promoter of
      Salmonella typhimurium.
AB  - Transcription from many bacterial promoters is sensitive to the level of DNA
      supercoiling. We have investigated the mechanism by which environmentally induced
      changes in DNA supercoiling might regulate transcription. For the proU promoter
      of Salmonella typhimurium, osmotically induced changes in DNA topology appear to
      play a primary regulatory role. Changes in DNA supercoiling (linking number;
      delta Lk) are partitioned into changes in the winding of the strands of the
      double helix about themselves (twist; delta Tw) and/or elastic deformations or
      flexibility of the DNA helix (writhe; delta Wr). Mutations of the proU promoter
      were isolated in vivo, or generated in vitro, which altered the spacing between
      the -10 and -35 motifs. Studies on these mutant promoters, both in vivo and in
      vitro, exclude models in which changes in DNA twist play a regulatory role.
      Instead, our data suggest that increased DNA flexibility, reflecting the
      osmotically induced increase in negative supercoiling of DNA, is required for
      promoter activation.

PMID- 8521827
TI  - Repression of cap-dependent translation by 4E-binding protein 1: competition with
      p220 for binding to eukaryotic initiation factor-4E.
AB  - An important aspect of the regulation of gene expression is the modulation of
      translation rates in response to growth factors, hormones and mitogens. Most of
      this control is at the level of translation initiation. Recent studies have
      implicated the MAP kinase pathway in the regulation of translation by insulin and
      growth factors. MAP kinase phosphorylates a repressor of translation initiation
      [4E-binding protein (BP) 1] that binds to the mRNA 5' cap binding protein
      eukaryotic initiation factor (eIF)-4E and inhibits cap-dependent translation.
      Phosphorylation of the repressor decreases its affinity for eIF-4E, and thus
      relieves translational inhibition. eIF-4E forms a complex with two other
      polypeptides, eIF-4A and p220, that promote 40S ribosome binding to mRNA. Here,
      we have studied the mechanism by which 4E-BP1 inhibits translation. We show that
      4E-BP1 inhibits 48S pre-initiation complex formation. Furthermore, we demonstrate
      that 4E-BP1 competes with p220 for binding to eIF-4E. Mutants of 4E-BP1 that are
      deficient in their binding to eIF-4E do not inhibit the interaction between p220
      and eIF-4E, and do not repress translation. Thus, translational control by growth
      factors, insulin and mitogens is affected by changes in the relative affinities
      of 4E-BP1 and p220 for eIF-4E.

PMID- 8521828
TI  - Novel location and function of a thyroid hormone response element.
AB  - We describe a novel thyroid hormone response element (TRE)-containing sequence,
      clone 144, isolated by immunoprecipitation of nuclear thyroid hormone receptor
      (TR)-DNA complexes from the rat pituitary tumor cell line GH4. These cells
      express several mRNAs of approximately 10 kb that hybridize to the TRE-containing
      genomic clone 144. These mRNAs are up-regulated at the transcriptional level in
      the absence of thyroid hormone (T3) and repressed in its presence. The sequence
      protected from DNase I digestion by TR in clone 144 contains two consensus TRE
      half-sites arranged as inverted palindromes. The clone 144 TRE is located in the
      3' untranslated region (UTR) of several related mRNAs. A reporter construct
      transfected into 293 cells was responsive to TR regulation when the clone 144 TRE
      was inserted in the 3' UTR but not when inserted upstream of the promoter. As
      found for the endogenous 144 mRNAs, the 144 TRE reporter construct is activated
      by TR in the absence of T3, but not in its presence. Deletion analysis showed
      that clone 144 sequences flanking the TRE were necessary for TR-mediated
      regulation, suggesting that the mechanism by which TR regulates transcription
      through a TRE in the 3' UTR is different from that through the TREs located in
      the promoter region.

PMID- 8521830
TI  - The E.coli RuvAB proteins branch migrate Holliday junctions through heterologous
      DNA sequences in a reaction facilitated by SSB.
AB  - During genetic recombination a heteroduplex joint is formed between two
      homologous DNA molecules. The heteroduplex joint plays an important role in
      recombination since it accommodates sequence heterogeneities (mismatches,
      insertions or deletions) that lead to genetic variation. Two Escherichia coli
      proteins, RuvA and RuvB, promote the formation of heteroduplex DNA by catalysing
      the branch migration of crossovers, or Holliday junctions, which link recombining
      chromosomes. We show that RuvA and RuvB can promote branch migration through 1800
      bp of heterologous DNA, in a reaction facilitated by the presence of E.coli
      single-stranded DNA binding (SSB) protein. Reaction intermediates, containing
      unpaired heteroduplex regions bound by SSB, were directly visualized by electron
      microscopy. In the absence of SSB, or when SSB was replaced by a single-strand
      binding protein from bacteriophage T4 (gene 32 protein), only limited
      heterologous branch migration was observed. These results show that the RuvAB
      proteins, which are induced as part of the SOS response to DNA damage, allow
      genetic recombination and the recombinational repair of DNA to occur in the
      presence of extensive lengths of heterology.

PMID- 8521829
TI  - Intron-encoded endonuclease I-TevI binds as a monomer to effect sequential
      cleavage via conformational changes in the td homing site.
AB  - I-TevI, the intron-encoded endonuclease from the thymidylate synthase (td) gene
      of bacteriophage T4, binds its DNA substrate across the minor groove in a
      sequence-tolerant fashion. We demonstrate here that the 28 kDa I-TevI binds the
      extensive 37 bp td homing site as a monomer and significantly distorts its
      substrate. In situ cleavage assays and phasing analyses indicate that upon
      nicking the bottom strand of the td homing site, I-TevI induces a directed bend
      of 38 degrees towards the major groove near the cleavage site. Formation of the
      bent I-TevI-DNA complex is proposed to promote top-strand cleavage of the homing
      site. Furthermore, reductions in the degree of distortion and in the efficiency
      of binding base-substitution variants of the td homing site indicate that
      sequences flanking the cleavage site contribute to the I-TevI-induced
      conformational change. These results, combined with genetic, physical and
      computer-modeling studies, form the basis of a model, wherein I-TevI acts as a
      hinged monomer to induce a distortion that widens the minor groove, facilitating
      access to the top-strand cleavage site. The model is compatible with both
      unmodified DNA and glucosylated hydroxymethylcytosine-containing DNA, as exists
      in the T-even phages.

PMID- 8521831
TI  - Tyrosine 114 is essential for the trimeric structure and the functional
      activities of human proliferating cell nuclear antigen.
AB  - In order to study the effect of trimerization of proliferating cell nuclear
      antigen (PCNA) on its interaction with DNA polymerase (pol) delta and its loading
      onto DNA by replication factor C (RF-C) we have mutated a single tyrosine residue
      located at the subunit interface (Tyr114) to alanine. This mutation (Y114A) had a
      profound effect on PCNA, since it completely abolished trimer formation as seen
      by glycerol gradient sedimentation and native gel electrophoresis. Furthermore,
      the mutant protein was unable to stimulate DNA synthesis by pol delta and did not
      compete effectively with wild-type PCNA for pol delta, although it was able to
      oligomerize and could to some extent interact with subunits of functionally
      active PCNA. We thus conclude that PCNA molecules that are not part of a circular
      trimeric complex cannot interact with the pol delta core. furthermore, the mutant
      protein could not be loaded onto DNA by RF-C and did not compete with wild-type
      PCNA for loading onto DNA, indicating that PCNA trimerization may also be a
      prerequisite for its recognition by RF-C. The adverse effects caused by this
      single mutation suggest that trimerization of PCNA is essential for the monomers
      to keep their overall structure and that the structural changes imposed by
      trimerization are important for interaction with other proteins.

PMID- 8521832
TI  - The calmodulin-binding domain of the inducible (macrophage) nitric oxide
      synthase.
AB  - A domain in the inducible, macrophage nitric oxide (NO) synthase has been
      selected as the putative calmodulin-binding site. The domain was synthesized as a
      peptide of 29 residues [P29, NO synthase-(504-532)-peptide], having the accepted
      hydrophobic/basic composition of calmodulin-binding domains and containing, like
      most of them, an aromatic amino acid at its N-terminus and a long chain aliphatic
      residue 12 amino acids downstream of it. A 34-residue peptide from the synthase
      sequence [P34, NO synthase-(499-532)-peptide], consisting of peptide P29 and of
      the five extra N-terminal amino acids, three of them basic, was also synthesized.
      Both peptides bound calmodulin in the presence as well as in the absence of Ca2+
      (i.e. in the presence of excess EGTA). The KD of the binding in the presence of
      Ca2+ was < or = 1 nM. The binding affinity was lower, but still remarkably high
      in the presence of EGTA. The peptides counteracted the stimulation by calmodulin
      of a classical calmodulin-target enzyme, the Ca2+ pump of the plasma membrane.

PMID- 8521833
TI  - Biochemical and functional properties of photosystem II in agranal membranes from
      maize mesophyll and bundle sheath chloroplasts.
AB  - We have studied the occurrence and organization of photosystem II (PSII) in
      bundle sheath thylakoids and stroma lamellae from maize. As shown by non
      denaturing lauryl beta-D- iminopropionidate (Deriphat)/PAGE, PSII exists in a
      dimeric form in grana membranes. In bundle sheath and stroma lamellae, however,
      only a monomeric form was found. Based on immunotitration data, we estimated the
      stoichiometry of the individual components of the PSII core complex and antenna
      systems. In stroma lamellae, all PSII antenna complexes had a stoichiometry
      similar to that in grana membranes, with the exception of light-harvesting
      complex II (LHCII) that was somewhat over-represented, while the minor antenna
      complexes CP26 and CP29 were under-represented. In bundle sheath, the amount of
      LHCII was approximately eight times higher than expected with respect to D1. The
      33-kDa protein of the oxygen-evolving enhancer polypeptides was not detectable
      nor was the ferredoxin-NADP+ reductase, thus strongly suggesting that no
      significant linear electron transport occurs in bundle sheath thylakoids.
      Fluorescence induction data suggest that most of the PSII reaction centers in
      bundle sheath and stroma lamellae sustain electron transport towards a secondary
      acceptor pool. Stromal PSII centers are only weakly inhibited by 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (diuron), whereas, unexpectedly,
      dichlorobenzoquinone and methyl viologen had a pronounced inhibitory effect of
      the QA- reoxidation. An additional specificity of these centers is the slow rate
      (50-ms range) of the QA to QB electron transfer. The amplitude of variable
      fluorescence found in stroma lamellae can only account for a small fraction (1
      2%) of the variable fluorescence of whole thylakoids. This suggests that stromal
      PSII cannot be solely responsible for the slow beta-phase of the induction
      kinetics.

PMID- 8521834
TI  - Purification of recombinant GluR-D glutamate receptor produced in Sf21 insect
      cells.
AB  - GluR-D glutamate receptors carrying FLAG and polyHis affinity tags at the N
      terminus and C-terminus, respectively, were expressed in recombinant baculovirus
      infected Spodoptera frugiperda Sf21 cells. Affinity-tagged receptors displayed
      ligand-binding affinity (Kd = 40 nM) and an expression level (Bmax 10-30 pmol/mg
      protein) similar to that of insect-cell-expressed wild-type GluR-D, as determined
      by [3H]-alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid ([3H]AMPA)
      binding. The receptor was solubilized in Triton X-100, and purified using a two
      step protocol consisting of immobilized metal-chelation affinity chromatography
      followed by immunoaffinity chromatography. The purified receptor preparation
      contained over 2000 pmol high-affinity [3H]AMPA-binding sites/mg protein, and
      migrated as a single 110-kDa species in SDS/PAGE. Peptide:N-glycosidase F
      treatment reduced the size of GluR-D from 110 kDa to 100 kDa, indicating the
      presence of N-linked glycans. Up to 100 micrograms purified GluR-D was obtained
      from 1 l Sf21 suspension culture (2-3 x 10(6) cells/ml). High-level expression of
      affinity-tagged GluRs in insect cells should be an efficient strategy to produce
      GluR subtypes for biochemical and structural studies.

PMID- 8521835
TI  - Biochemical characterization of the 8-hydroxy-5-deazaflavin-reactive hydrogenase
      from Methanosarcina barkeri Fusaro.
AB  - The membrane-associated coenzyme F420-reactive hydrogenase of the anaerobic
      methanogenic archaeon Methanosarcina barkeri Fusaro has been purified 95-fold to
      apparent homogeneity. A new purification procedure and altered storage conditions
      gave substantially higher yield (13.4% versus 4.3%) and specific coenzyme F420
      reducing activity (82.8 mumol.min-1.mg protein-1 versus 11.5 mumol.min-1.mg
      protein-1) than reported previously [Fiebig, K. & Friedrich, B. (1989) Eur. J.
      Biochem. 184, 79-88]. The predominant coenzyme F420-reactive form of the
      hydrogenase has an apparent molecular mass of 198 kDa and is composed of three
      non-identical subunits with apparent molecular masses of 48 (alpha), 33 (beta),
      and 30 kDa (gamma), apparently in a stoichiometry of alpha 2 beta 2 gamma 1. This
      minimal coenzyme F420-reducing hydrogenase formed aggregates with apparent
      molecular masses of approximately 845 kDa. 1 mol of the 198-kDa form of
      hydrogenase contained 2 mol FAD, 2 mol nickel, 28-32 mol non-heme iron, and 34
      mol acid-labile sulfur; in addition, 0.2 mol selenium was detected. The
      isoelectric point was 5.30. The amino acid sequence PXXRXEGH, where X is any
      amino acid, was found to be conserved in the N-termini of the putative nickel
      binding subunits of most [NiFe]- and [NiFeSe]hydrogenases of methanogenic Archaea
      and Bacteria. However, this motif was not detected in the protein sequences of
      [Fe]hydrogenases. Maximal coenzyme F420-reducing activity was obtained with
      reductively reactivated enzyme at 55 degrees C in the pH range 6.5-7.25. The Km
      values of the purified enzyme for H2 with coenzyme F420 or methylviologen as
      electron acceptor were extremely low, namely 3 microM and 4 microM. The catalytic
      efficiency coefficients (kcat/Km) for H2 with both reducible cosubstrates were
      high: 2.5 x 10(7) M-1.s-1 with coenzyme F420 and 6.9 x 10(7) M-1.s-1 with
      methylviologen.

PMID- 8521836
TI  - Characterisation of a second, apparently inactive, copy of the bovine beta
      lactoglobulin gene.
AB  - A bovine cosmid clone was isolated which contains the previously characterised
      beta-lactoglobulin gene and, in addition, a related sequence which appears to be
      a beta-lactoglobulin pseudogene. The total length of the pseudogene, as
      determined by DNA sequencing, is 4.8 kb, similar to that of beta-lactoglobulin.
      Both genes are in the same orientation and are separated by approximately 14 kb
      intergenic sequence. Although most of introns I-V are extremely divergent, the
      exon sequences are clearly related, exons I-V exhibiting nucleotide sequence
      similarities in the range 60-87%. Exons VI and VII, together with the final
      intron, comprise a region of sequence extending over 730 bp, which displays 92.5%
      identity to the corresponding beta-lactoglobulin sequence. It is suggested that
      this is the result of a recent gene conversion event involving conversion of the
      pseudogene by the authentic beta-lactoglobulin gene. Identification of the new
      lactoglobulin  sequence as a pseudogene is based on the occurrence of a stop
      codon in exon V. Comparison of the inferred translation product encoded by the
      pseudogene before its mutational inactivation, with the sequences of equine and
      feline beta-lactoglobulins I and II, indicates that the bovine pseudogene is more
      closely related to these type-II lactoglobulin sequences than to the type-I
      sequences.

PMID- 8521837
TI  - A precursor-product relationship in molluscan sperm proteins from Ensis minor.
AB  - A cDNA library prepared from mRNA extracted from immature male gonads of the
      bivalve mollusc Ensis minor (razor shell) was probed with a 133-bp reverse
      transcriptase PCR product corresponding to a segment of the sperm protein EM6
      [Giancotti, V., Russo, E., Gasparini, M., Serrano, D., Del Piero, D., Thorne, A.
      W., Cary, P.D. & Crane-Robinson, C. (1993) Eur. J. Biochem. 136, 509-516]. A
      single 1.5-kb clone was found to encode both sperm proteins EM1 and EM6. Mass
      spectrometry was used to define the C-terminus of EM1, and since the N-terminus
      of EM6 is known from Edman degradation, this showed that the pentapeptide NTNNS
      must be lost on proteolytic processing. Both EM1 and EM6 contain highly repeated
      amino acid sequences, suggestive of extended structures. EM1 contains seven
      tandem repeats of the dipeptide S(K/R), followed by six potential cdc2
      phosphorylation sites and seven repeats of the octapeptide KRSASKKR, with
      occasional K/R substitutions. EM6 contains a globular domain preceded by 17
      almost identical uninterupted tandem repeats of the motif KKRSXSRKRSAS, where X
      is charged. Its C-terminus contains 15 short basic clusters. Assignment of EM1
      and EM6 to the established categories of molluscan sperm proteins [PLI, PLII,
      PLIII, PLIV; Ausio, J. (1992) Mol. Cell. Biochem. 115, 163-172] is discussed.

PMID- 8521838
TI  - His103 in yeast transketolase is required for substrate recognition and
      catalysis.
AB  - Crystallographic studies of thiamin-diphosphate-dependent transketolase from
      Saccharomyces cerevisiae suggested the invariant active-site residue H103 as a
      possible enzymic group binding the C1 hydroxyl group of the donor substrate and
      stabilizing the reaction intermediate. To test this hypothesis, H103 was replaced
      by alanine, asparagine and phenylalanine using site-directed mutagenesis. The
      crystallographic analysis of the mutant transketolases verified that no
      structural changes occurred as a consequence of the side-chain replacements. The
      residual catalytic activities of the mutant enzymes were 4.3% for the H103A, 2.4%
      for the H103N and 0.1% for the H103F mutant transketolase. Further kinetic
      analysis of the H103A and H103N mutant enzymes showed that the Km values for the
      coenzyme were increased by about eightfold. The Km values for the acceptor
      substrate ribose 5-phosphate were similar to the Km value for wild-type
      transketolase. However, the Km value for the donor substrate, xylulose 5
      phosphate is increased more than tenfold in these two mutants. Circular dichroism
      spectra of the mutant enzymes also indicated a weaker binding of the donor
      substrate and/or a less stable reaction intermediate. These observations provide
      further evidence in support of the proposed role for this invariant residue in
      recognition of the donor substrate by forming a hydrogen bond between the side
      chain of H103 and the C1 hydroxyl group of the sugar phosphate. The significant
      decrease in catalytic activity suggests that this residue also facilitates
      catalysis, possibly by maintaining the optimal orientation of the donor substrate
      and reaction intermediates.

PMID- 8521839
TI  - Afaacytin, an alpha beta-fibrinogenase from Cerastes cerastes (horned viper)
      venom, activates purified factor X and induces serotonin release from human blood
      platelets.
AB  - Afaacytin, a proteinase with caseinolytic, arginine-esterase and amidase
      activities, was purified from the venom of Cerastes cerastes (horned viper) in
      two steps by gel filtration through Sephadex G75, then HPLC on carboxymethyl
      cellulose. Afaacytin has an isoelectric point of 6.25, and consists of two
      subunits, alpha and beta, which have the same apparent molecular mass (40,000)
      and are indistinguishable in the absence of reduction or/and deglycosylation.
      Subunit beta is constituted of two disulfide-linked polypeptidic chains, beta and
      beta'. The respective apparent molecular mass of the chains are 43,000 (alpha),
      35,500 (beta) and 10,200 (beta') as determined by SDS/PAGE under reducing
      conditions. Both chains alpha and beta are N-glycosylated. The two chains have
      the same N-terminal sequence (20 residues) which is similar to those of other
      proteinases from snake venom. Susceptibility of afaacytin to diisopropyl
      fluorophosphate and benzamidine indicates the presence of a serine and an
      aspartic (or glutamic) acid residues in the catalytic site. Ca2+ appears to be
      required for structural cohesion of the afaacytin molecule. Afaacytin exhibits
      alpha beta-fibrinogenase and alpha-fibrinase properties. It replaces missing
      factors VIII and IX in deficient plasmas, and activates purified human factor X
      into factor Xa. It releases serotonin from platelets and directly aggregates
      human (but not rabbit) blood platelets. Despite its thrombin-like
      characteristics, however, afaacytin is not inhibited by plasmatic thrombin
      inhibitors. The procoagulant properties of afaacytin therefore have potential
      clinical applications.

PMID- 8521840
TI  - The functional integration of a polytopic membrane protein of Escherichia coli is
      dependent on the bacterial signal-recognition particle.
AB  - In eukaryotes, the cotranslational targeting of proteins to the endoplasmic
      reticular membrane is initially mediated by the signal-recognition particle
      (SRP), a ribonucleoprotein complex consisting of the 7SL RNA and six protein
      subunits. Since the discovery of sequence homology between (a) the Escherichia
      coli 4.5S RNA (Ffs) and 7SL RNA, and (b) the E. coli P48 (Ffh) and SRP 54-kDa
      subunit, more evidence has been obtained that E. coli also possesses an SRP-type
      pathway that acts in the translocation of secreted proteins. Such a pathway could
      possibly be involved in the cotranslational integration of hydrophobic membrane
      proteins that cannot be effectively targeted post-translationally due to folding
      and aggregation. In this study, we report that disruption of the E. coli SRP
      complex with a dominant lethal 4.5S RNA mutant in vivo prevents functional
      membrane integration of the E. coli lactose permease (LacY). Likewise, depletion
      of the P48 (Ffh) protein also results in a decrease in the amount of functional
      LacY inserted into the E. coli plasma membrane. In direct contrast, inhibition of
      SecA function does not affect LacY integration. These results suggest a major
      function of the bacterial SRP in the targeting and subsequent integration of
      hydrophobic membrane proteins as opposed to SecA mediating the post-translational
      targeting of secretory proteins.

PMID- 8521841
TI  - Expression of functional ricin B chain using the baculovirus system.
AB  - The ricin B chain (RTB) was expressed using a baculovirus expression system. The
      RTB coding sequence downstream of the preproricin signal sequence was inserted in
      the baculovirus transfer vector pM34T. After cotransfection of Spodoptera
      frugiperda Sf9 cells with linearized baculovirus DNA, recombinant viruses were
      selected, cloned and amplified. Upon infection of Sf9 cells with these
      recombinant baculoviruses, RTB production was revealed by immunoblotting. RTB
      expression using this system was optimum 72 h after infection of the cells at a
      multiplicity of infection of 3. RTB produced was glycosylated and had an apparent
      molecular mass of 34 kDa. Most of the signal sequence was removed, but the
      resulting recombinant RTB had a 13-residue N-terminus extension.
      Immunofluorescence analysis showed that this protein was located in the
      endoplasmic reticulum/Golgi region of the cell. RTB was not present at the plasma
      membrane. Secretion was enhanced by the addition of lactose to the cell-culture
      medium up to 50 mM. Purification was achieved from both cells and media using
      immobilized lactose and the lectin activity of RTB. Results obtained with the
      purified recombinant protein (more than 2 mg/l culture) were identical to those
      obtained with native RTB in all assays for biological activity; binding,
      internalization and reassociation with the ricin A chain to produce toxic ricin.
      Moreover, the RTB translocation capacity was not altered by the N-terminal
      peptide, showing that recombinant RTB could be used to deliver antigenic peptides
      to the cytosol for the induction of cell-mediated immunity.

PMID- 8521842
TI  - A novel membrane glycoprotein involved in ascidian hemocyte aggregation and
      phagocytosis.
AB  - Invertebrate hemocytes undergo several cellular defense reactions. To clarify the
      molecular mechanisms for cellular recognition between hemocytes and also between
      hemocytes and foreign materials, we established hybridoma clones producing
      monoclonal antibodies that inhibit hemocyte aggregation (i.e. a cellular reaction
      between hemocytes) in the solitary ascidian, Halocynthia roretzi. The antibody,
      A74, also inhibited phagocytosis of foreign materials by H. roretzi hemocytes.
      Immunocytochemistry of H. roretzi hemocytes using A74 antibody revealed the
      localization of the A74 antigen on the surface of hemocytes. The A74 antigen,
      which is referred to as A74 protein, was purified from a hemocyte membrane
      preparation by three chromatographies on phenyl-Sepharose, A74 antibody
      immobilized Sepharose and Mono Q. The A74 protein was a glycoprotein with a
      molecular mass of 160 kDa; N-glycosidase or neuraminidase treatment resulted in a
      reduction of its molecular mass. The N-terminal amino acid sequence of A74
      protein showed little similarity to other known proteins. Thus, the A74 protein
      is a novel membrane protein that plays an important role in ascidian cellular
      defense reactions.

PMID- 8521843
TI  - Cordycepin blocks recovery of non-heat-shock mRNA translation following heat
      shock in Drosophila.
AB  - Treatment of cells with cordycepin (3-deoxyadenosine), an inhibitor of
      cytoplasmic adenylation, blocks the restoration of normal translation following
      heat shock. Cordycepin also reduces heat-shock protein 70 (Hsp70) protein
      synthesis greater than 10-fold, while having little to no effect on mRNA
      accumulation. Parallel analysis of the poly(A)-binding protein detects no change
      in its abundance during heat shock or subsequent recovery. These results suggest
      that normal, non-heat-shock mRNA translational repression during heat shock may
      be caused by deadenylation, and that readenylation is required for restoration of
      activity. However, three independent analyses of the adenylation status of mRNAs
      during heat shock and recovery indicate that no significant changes in
      polyadenylation occur. (a) The total poly(A) content decreases by only about 10%
      during heat shock; (b) the size of the poly(A) tract decreases only marginally,
      from an average length of 75-90 nucleotides in non-heated cells to 45-60
      nucleotides during heat shock; (c) virtually all mRNAs bind to oligo d(T)
      cellulose, whether extracted from normal-temperature, heat-shock or recovered
      cells. Our results are most consistent with a model where the process of
      readenylation, rather than the specific poly(A) tail length, influences
      translational activation during recovery, paralleling a proposed model for the
      activation of translation during Xenopus oocyte maturation.

PMID- 8521844
TI  - A CCACC motif mediates negative transcriptional regulation of the human
      erythropoietin receptor.
AB  - We have previously shown that the +79 to +135 fragment of the human
      erythropoietin receptor (Epo-R) acts negatively on the transcriptional activity
      and confers erythroid specificity to the gene [Maouche, L., Cartron, J.-P. &
      Chretien, S. (1994) Nucleic Acids Res. 22, 338-346]. In this work, we demonstrate
      that this effect is mediated by a CCACC motif that binds weakly to the simian
      virus 40 protein 1 (Sp1) factor and that the increase of the affinity for Sp1
      augments transcription inhibition. The repression is not restricted to the human
      Epo-R promoter, although it seems more efficient on heterologous promoters of
      erythroid genes. In chloramphenicol acetyl transferase constructs containing the
      mouse Epo-R promoter, rearranged by retroviral long terminal repeat (LTR)
      insertion of murine erythroleukemia cell lines, we found that positioning the
      CCACC motif 3' to the LTR represses the transcriptional activity mediated by the
      LTR in non-erythroid cells. These results demonstrate that Epo-R gene expression
      is negatively regulated by a CCACC or a GC box-binding factor, which is most
      likely identical to the Sp1 transcription protein. Further data suggest that Sp1
      mediated negative regulation is not the result of a direct competition between
      Sp1 and another DNA-binding protein.

PMID- 8521845
TI  - The phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase genes
      from the thermophilic archaeon Sulfolobus solfataricus overlap by 8-bp.
      Isolation, sequencing of the genes and expression in Escherichia coli.
AB  - The overlapping genes encoding phosphoglycerate kinase (PGK) and glyceraldehyde-3
      phosphate dehydrogenase (GraP-DH) from the hyperthermophilic archaeon Sulfolobus
      solfataricus have been cloned and sequenced. PCR primers based on highly
      conserved regions of different PGK sequences were used to isolate an internal
      region of the pgk gene. This was then used to screen a genomic library to isolate
      the full length pgk gene. A 2.5-kb BglII fragment of S. solfataricus DNA
      contained both the pgk gene and the gap gene immediately downstream.
      Unexpectedly, the pgk and gap genes were found to overlap by 8 bp, with the
      initiation codon of the gap gene preceding the termination codon of the pgk gene.
      Evidence that the two genes are co-transcribed was obtained by Northern-blot
      analysis. The S. solfataricus PGK amino acid sequence shows 43% and 45% identity
      to the PGK sequences of the Archaea Methanobacterium bryantii and Methanothermus
      fervidus, respectively. High level expression of the S. solfataricus PGK and GraP
      DH in Escherichia coli was achieved, with heat treatment at 80 degrees C proving
      an effective first step in the purification of these recombinant enzymes from
      extracts of the E. coli host. Purified recombinant S. solfataricus PGK and GraP
      DH showed half lives of 39 min and 17 h, respectively, at 80 degrees C. Unlike
      bacterial GraP-DH enzymes, S. solfataricus GraP-DH was able to use both NAD+ and
      NADP+ as cofactors, but exhibited a marked preference for NADP+.

PMID- 8521846
TI  - Absolute requirement of ammonium sulfate for reconstitution of active 70S
      ribosomes from the extreme halophilic archaeon Haloferax mediterranei.
AB  - Active 70S ribosomes from the halophilic archaeon Haloferax mediterranei have
      been reconstituted from their isolated rRNAs and proteins. The reconstitution
      procedure consists of a two-step incubation; first with 1 M ammonium sulfate and
      100 mM magnesium acetate for 1 h at 42 degrees C, followed by a 90-min incubation
      at 50 degrees C after increasing the ammonium sulfate to 2 M final concentration.
      The total reconstitution of halophilic 70S ribosomes is a process with its own
      identity, which does not correspond to the conditions required for the
      reconstitution of the isolated subunits. Ammonium sulfate is the only salt
      capable of promoting the assembly of active ribosomes. The increase of ammonium
      sulfate salts in the second incubation step is obligatory for the isolation of
      functional particles.

PMID- 8521847
TI  - Characterization of the lower-molecular-mass fraction of venoms from Dendroaspis
      jamesoni kaimosae and Micrurus fulvius using capillary-electrophoresis
      electrospray mass spectrometry.
AB  - Capillary electrophoresis (CE) with electrospray ionization (ESI) and selected
      ion-monitoring mass-spectrometric (SIM-MS) detection has been used to provide as
      much information as possible about the lower molecular-mass fraction (peptides of
      molecular masses up to 8500 Da) of the venoms of Dendroaspis jamesoni kaimosae
      (Jameson's Mamba) and Micrurus fulvius (Eastern Coral Snake). Method development
      was based on the venom of D. jamesoni kaimosae, which contains some previously
      described peptides, with subsequent application to the completely unknown venom
      of M. fulvius. CE-ESI-SIM-MS provides a rapid and extremely sensitive method for
      the detection and molecular-mass determination of peptides present in venoms. It
      has been utilized to provide molecular masses and thus, by inference,
      confirmation of the peptide compositions for those toxins which have been
      previously described in the literature. Our methodology indicates the presence of
      83 peptides in the venom of D. jamesoni kaimosae and 49 peptides in the venom of
      M. fulvius in the molecular-mass range 6000-8500 Da.

PMID- 8521848
TI  - Purification of active E1 alpha 2 beta 2 of Pseudomonas putida branched-chain
      oxoacid dehydrogenase.
AB  - Active E1 component of Pseudomonas putida branched-chain-oxoacid dehydrogenase
      was purified from P. putida strains carrying pJRS84 which contains bkdR (encoding
      the transcriptional activator) and bkdA1 and bkdA2 (encoding the alpha and beta
      subunits). Expression was inducible, however, 45-, 39- and 37-kDa proteins were
      produced instead of the expected 45-kDa and 37-kDa proteins. The 45-kDa protein
      was identified as E1 alpha and the 37-kDa and 39-kDa proteins were identified as
      separate translational products of bkdA2 by their N-terminal sequences. The N
      terminal amino acid of the 39-kDa protein was leucine instead of methionine. The
      45-, 39- and 37-kDa proteins were also produced in wild-type P.putida.
      Translation of bkdA1 and bkdA2 from an Escherichia coli expression plasmid
      produced only 45-kDa and 39-kDa proteins, with N-terminal methionine on the 39
      kDa protein. The insertion of guanine residues 5' to the first ATG of bkdA2 did
      not affect expression of E1 beta in P. putida including the N-terminal leucine
      which appears to eliminate the possibility of ribosome jumping. The Z-average
      molecular mass of the E1 component was determined by sedimentation equilibrium to
      be 172 +/- 9 kDa compared to a calculated value of 166 kDa for the heterotetramer
      and a Stokes radius of 5.1 nm. E1 alpha Ser313, which is homologous to the
      phosphorylated residue of rat liver E1 alpha, was converted to alanine resulting
      in about a twofold increase in Km, but no change in Kcat. S315A and S319A
      mutations had no effect on Km or Kcat indicating that these residues do not play
      a major part in catalysis of E1 alpha beta 2.

PMID- 8521849
TI  - Folding of the squash trypsin inhibitor EETI II. Evidence of native and non
      native local structural preferences in a linear analogue.
AB  - A peptide, corresponding to the entire sequence of the squash trypsin inhibitor
      EETI II (Ecballium elaterium trypsin inhibitor) in which the six cysteines,
      engaged in three disulphide bridges in native EETI II, have been replaced by six
      serines, has been synthesised. CD, Fourier-transform infrared spectroscopy (FTIR)
      and 1H-NMR studies of this peptide revealed that some secondary structures
      present in native EETI II are still populated in the absence of disulphide bonds.
      Native-like secondary structures were observed for segments 10-15 (helix), 16-19
      and 22-25 (reverse turns) but no native tertiary interaction was detected.
      However, a non-native local interaction between the aromatic ring of Phe26 and
      the amide group of Gly28 was observed. It is hypothesised that the 10-15, 16-19
      and 22-25 native-like local conformations could play a major role in the early
      folding of EETI II.

PMID- 8521850
TI  - NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide.
      Similarities to porcine spasmolytic peptide and evidence for a monomeric
      structure.
AB  - NMR spectroscopy measurements have been used to obtain structural information
      about the pNR-2/pS2 single-domain trefoil peptide. NMR data from 2D (two
      dimensional) double-quantum-filtered correlation spectroscopy (DQF-COSY), total
      correlation spectroscopy (TOCSY), NOE spectroscopy (NOESY), rotating frame NOE
      spectroscopy (ROESY) and 2D 13C-1H heteronuclear single-quantum coherence (HSQC)
      and 13C-1H HSQC-TOCSY spectra have been analysed to provide essentially complete
      1H and 13C sequence-specific assignments for the pNR-2/pS2 protein. From a
      consideration of the NOE intensities, 3J(NH-alpha CH) coupling constants, 1H and
      13C chemical shifts of backbone atoms and amide-proton exchange rates, the pNR
      2/pS2 was found to contain two short antiparallel beta-strands (32-35 and 43-46),
      a short helix (25-30) and a type I beta-turn (11-15). These elements of secondary
      structure are very similar to those found in the two trefoil domains of pSP for
      which detailed structural information is already available. Similar 1H chemical
      shifts were noted for several conserved residues in pNR-2/pS2 and pSP and a
      characteristic Phe residue with a slowly flipping ring was found in the pNR-2/pS2
      variant and in both domains of pSP. The tertiary structures of the domains
      therefore appear to be very similar in the two proteins and it is likely that the
      pNR-2/pS2 has the same pattern of disulphide bonds (1-5, 2-4, 3-6) as pSP.
      Correlation time measurements derived from 1H-1H NOE measurements indicate that
      the Cys58-->Ser form of the pNR-2/pS2 protein used in this study is monomeric in
      solution at approximately 2 mM.

PMID- 8521851
TI  - High-affinity interaction of human immunodeficiency virus type-1 reverse
      transcriptase with partially complementary primers.
AB  - The comparison of Km and Vmax values for various primers in the reaction of
      polymerization catalyzed by the human immunodeficiency virus type-1 (HIV-1)
      reverse transcriptase was carried out. The primers were: (a) complementary to the
      template, (b) partially complementary with mismatched nucleotides at different
      positions from the 3' end or (c) non-complementary. Non-complementary primers
      were not elongated by HIV-1 reverse transcriptase. However, if they contained
      only one residue complementary to the template or an abasic unit at the 3' end,
      they could serve as primers. The most effective discrimination between matched
      and mismatched primers, due to a decrease in the affinity and Vmax, was found in
      the case of oligonucleotides containing non-complementary bases at the second or
      third position from the 3' end of the primer. The efficiency of discrimination by
      HIV-1 reverse transcriptase between matched and mismatched base-paired primers
      was about 1-1.5 orders of magnitude lower than that of procaryotic, eucaryotic
      and archaebacterial DNA polymerases and avian myeloblastosis virus reverse
      transcriptase. Oligonucleotides such as (dT)4(dCdG)k(dT)4 showed higher affinity
      for the enzyme than (dT)4 or (dT)8 primers. These data suggest that HIV-1 reverse
      transcriptase, in contrast to procaryotic, eucaryotic and archaebacterial DNA
      polymerases, forms additional contacts with the 5'-end region of the non
      complementary primer. In addition, using tRNA(3Lys), the natural primer of HIV-1,
      it was shown that the p66 subunit of reverse transcriptase can be crosslinked, in
      the presence of a platinum derivative, to the 5' end of tRNA. Thus, besides the
      normal binding site for the 3' end of tRNA, which is crucial for the initiation
      of cDNA synthesis, the 5' end of the tRNA also interacts with a specific site on
      the enzyme.

PMID- 8521852
TI  - Carotene desaturation is linked to a respiratory redox pathway in Narcissus
      pseudonarcissus chromoplast membranes. Involvement of a 23-kDa oxygen-evolving
      complex-like protein.
AB  - The enzymic activity of phytoene desaturase in Narcissus pseudonarcissus
      chromoplast membranes depends in an essential way on the redox state of its
      environment. Here, the main redox-active components are quinones and tocopherols.
      Quinones (oxidized) act as intermediate electron acceptors in the desaturation
      reaction, as can be shown in reduced, hydroquinone-rich membranes. However, their
      complete oxidation by ferricyanide treatment of membranes leads to inhibition of
      the desaturation activity and, under these conditions, hydroquinones are required
      for reactivation. Using redox titrations, it is shown here that the optimal
      activity lies in the range of the midpoint potential of the
      plastoquinone/plastohydroquinone redox couple. For the adjustment of redox states
      of the redox-active lipid components in (photosynthetically inactive)
      chromoplasts, NADPH and oxygen are involved, the latter acting as a terminal
      acceptor. This results in a respiratory redox pathway in chromoplast membranes
      which is described here, to our knowledge, for the first time. Since phytoene
      desaturation responds to the redox state of quinones, which is adjusted by the
      respiratory redox pathway, the two reactions must be regarded as being
      mechanistically linked. The first protein component involved in the respiratory
      pathway which we have investigated molecularly is a 43-kDa NAD(P)H:quinone
      oxidoreductase, which is organized as a homodimer (23 +/- 3 kDa/subunit) and
      apparently possesses a manganese redox center. Internal protein microsequencing
      and cloning of the corresponding cDNA revealed a high degree of similarity to the
      23-kDa protein of the oxygen-evolving complex of photosystem II, but no
      information about the N-terminal organization of the oxidoreductase could be
      obtained. During flower development, the steady-state concentration of the
      corresponding mRNA is up-regulated, indicating a specific function of the gene
      product in chlorophyll-free chromoplasts.

PMID- 8521853
TI  - Molecular properties of the dissimilatory sulfite reductase from Desulfovibrio
      desulfuricans (Essex) and comparison with the enzyme from Desulfovibrio vulgaris
      (Hildenborough).
AB  - The dissimilatory sulfite reductase desulfoviridin was purified from the membrane
      (mSiR) and the soluble fraction (sSiR) of the sulfate-reducing bacterium
      Desulfovibrio desulfuricans (Essex). Molecular and spectroscopic properties were
      determined and compared with the properties of the soluble desulfoviridin from
      Desulfovibrio vulgaris (Hildenborough). The enzymes were isolated as alpha 2 beta
      2 gamma n (n = 1-3) multimers with a relative molecular mass of 200 +/- 10 (gel
      filtration). Both mSiR and sSiR from D. desulfuricans contained 24 +/- 3 Fe and
      18 +/- 3 labile sulfide/200 kDa, respectively, and showed identical EPR spectra.
      Quantification of the high-spin Fe(III) heme resonances at g of approximately 6
      indicated that close to 80% of the siroheme moiety in the enzyme from D.
      desulfuricans was demetallated. D. desulfuricans sulfite reductase showed S = 9/2
      EPR signals with the highest apparent g value at g = 17 as reported for SiR from
      D. vulgaris. Antibodies raised against the alpha, beta and gamma subunit of the
      D. vulgaris enzyme exhibited cross-reactivity with the subunits of mSiR and sSiR
      from D. desulfuricans. N-terminal sequences of alpha, beta and gamma subunits of
      both mSiR and sSiR from D. desulfuricans were identical and showed a high degree
      of similarity with the sequences of the corresponding subunits obtained from the
      D. vulgaris enzyme. During gel filtration of sSiR from D. desulfuricans, under
      non-denaturing conditions, a small protein (molecular mass approximately 11 kDa)
      was separated. This 11-kDa protein exhibited cross-reactivity with the antibody
      raised against the gamma subunit of D. vulgaris sulfite reductase. In the case of
      D. desulfuricans sulfite reductase, the 11-kDa gamma subunit seems not to be an
      integral part of the protein and can be obtained from the soluble fraction and
      during purification of the soluble enzyme.

PMID- 8521854
TI  - Affinity labeling of recombinant ricin A chain with Procion blue MX-R.
AB  - Recombinant ricin A chain was irreversibly modified by Procion blue MX-R, a
      dichlorotriazinyl analogue of Cibacron blue F3G-A, at pH 7.5 and 4 degrees C in
      90 h with over 95% loss of activity in an in vitro translation assay. The
      presence of total yeast RNA reduced the covalent attachment of Procion blue MX-R
      to ricin A chain. Quantitatively modified ricin A chain contained 2 mol Procion
      blue MX-R/mol 29-kDa subunit. Tryptic digestion and resolution of the peptides by
      reverse-phase high-performance liquid chromatography yields a blue peptide
      corresponding to Gln5-Arg26 of ricin A chain. Thus, a likely dye-binding site on
      recombinant ricin A was identified. This region is removed from the active-site
      cleft of recombinant ricin A but may be involved in its substrate binding.

PMID- 8521855
TI  - 2-Chloro-2'-deoxyadenosine (cladribine) and its analogues are good substrates and
      potent selective inhibitors of Escherichia coli purine-nucleoside phosphorylase.
AB  - 2-Chloro-2'-deoxyadenosine (CldAdo), a nucleoside that has proven useful in the
      treatment of several chronic lymphoid malignancies, and its analogue, 2-bromo-2'
      deoxyadenosine, are both effective inhibitors of the bacterial (Escherichia coli)
      purine-nucleoside phosphorylase (PNP), with Ki values of 4.5 microM and 6.3
      microM, respectively. The examination of a series of base-modified analogues of
      CldAdo has shown that several other compounds have similar inhibitor properties,
      and has indicated that 6-benzyloxy-2-chloro-9-(2'-deoxy-beta-D
      ribofuranosyl)purine is the most potent inhibitor with a Ki value of 0.5 microM,
      competitive with respect to inosine (Ino). CldAdo itself and its base-modified
      analogues, discounting those substituted at C(8), are also substrates for the E.
      coli PNP and undergo rapid glycosidic bond cleavage. CldAdo is degraded with
      substrate efficiency, i.e. Vmax/Km similar to that observed for Ino (130%),
      although the individual kinetic constants, Km and Vmax, are both approximately an
      order of magnitude lower than for Ino. All compounds tested are totally inactive
      as substrates and inhibitors for mammalian (calf spleen) PNP and therefore
      constitute a new class of potent selective, although cleavable, inhibitors of
      bacterial phosphorylases. 8-Bromo-2-chloro-2'-deoxyadenosine and 8-thio-2-chloro
      2'-deoxyadenosine are the only base-modified CldAdo derivatives showing
      inhibitory activity against MOLT-3 (acute T-cell leukemia) and U-937 (histiocytic
      lymphoma) cells and, as shown in this study, are resistant to degradation by E.
      coli PNP. The above-mentioned results suggest that both analogues could be
      effective as oral cytotoxic agents that are noncleavable by enteric bacteria.

PMID- 8521856
TI  - Effect of pH on sheep liver sorbitol dehydrogenase steady-state kinetics.
AB  - The variation with pH of the kinetic parameters for sorbitol oxidation and
      fructose reduction by sheep liver sorbitol dehydrogenase has been studied over
      the pH 5-10 range. The reaction is compulsory ordered in both directions with the
      coenzyme as the leading substrate, and the rate-determining step in either
      direction is the enzyme-coenzyme product dissociation. Throughout the pH range,
      the lack of a primary kinetic isotope effect on Vm with (2H8) sorbitol confirms
      that the ternary complexes are not of rate-determining significance under maximum
      velocity conditions. The association rate constants for NAD and NADH increase and
      decrease, respectively, towards high pH. NAD binding to the enzyme is dependent
      upon pK values of 9.2 and 9.6. Whereas the dissociation rate constant for NAD
      release from the enzyme shows no pronounced variation with pH, NADH release is
      dependent upon pK values of 7.2 and 7.7. The kinetic constants that characterize
      the dependence on substrate concentration of the steady-state rate of catalysis
      vary with pH in accordance with a single pK of 7.1 for sorbitol oxidation and of
      7.7 for fructose reduction. These pK values reflect the ionization properties of
      a catalytically essential group, which is tentatively considered to be either the
      H2O/OH- ligand binding to the catalytic zinc atom or a histidine residue.
      Catalysis by sorbitol dehydrogenase, due to the absence of a second ionization
      contribution, appears not to involve any obligatory step of proton transfer to
      solution at the ternary complex level. A mechanism for sorbitol dehydrogenase
      catalysis is proposed.

PMID- 8521857
TI  - Structural studies of the putative O-specific polysaccharide of Acinetobacter
      baumannii O2 containing 3,6-dideoxy-3-N-(D-3-hydroxybutyryl)amino-D-galactose.
AB  - A polysaccharide containing D-galactose, 2-deoxy-2-N-acetylamino-D-galactose and
      3,6-dideoxy-3-N-(D-3-hydroxybutyryl)amino-D-galactose, probably corresponding to
      the lipopolysaccharide side chain, was obtained from an aqueous phenol extract of
      isolated cell walls from Acinetobacter baumannii strain O2. By means of NMR
      studies and chemical degradations, the repeating unit of the polymer was
      identified as a branched hexasaccharide of the structure shown, where Fuc3N
      represents 3-amino-3,6-dideoxygalactose and R represents D-3-hydroxybutyryl.
      Serological tests indicated that the polymer corresponded to the O2 antigen.

PMID- 8521858
TI  - Triggering of a phospholipase D pathway upon mitogenic stimulation of human
      peripheral blood mononuclear cells enriched with 12(S)-hydroxyicosatetraenoic
      acid.
AB  - The influence of 12(S)-hydroxyicosatetraenoic acid (12-HETE), that we have
      previously shown to decrease the proliferative response of human lymphocytes to
      mitogens, on diacylglycerol and phosphatidic acid (PtdOH) formation was
      investigated in stimulated human peripheral blood mononuclear cells (PBMC). When
      human PBMC were first enriched with 12-HETE, then stimulated by the mitogenic
      lectin concanavalin A (Con A), the production of PtdOH normally associated with
      Con A stimulation was markedly increased as compared with non-enriched cells. The
      Con-A-induced rise in the PtdOH mass was markedly decreased by 1% ethanol in 12
      HETE-enriched cells, whereas it was unaffected in control cells stimulated by Con
      A alone. Furthermore, in [3H]arachidonic-acid-labelled cells previously enriched
      with 12-HETE, the formation of [3H]arachidonic-acid-labelled phosphatidylalcohol
      was significantly increased upon Con A stimulation, no phosphatidylalcohol being
      synthesized in non-enriched cells. Collectively, these results suggest that, in
      the presence of 12-HETE, Con A stimulates a phospholipase D activity which was
      not triggered by Con A alone. These data are consistent with the lack of effect
      of suramin, reported as a phospholipase D inhibitor, which we observed in cells
      stimulated by Con A alone and with the suramin-induced decrease of PtdOH mass in
      12-HETE-plus-Con-A-treated cells. Moreover, 12-[3H]HETE-enriched PBMC produced a
      significant amount of 12-[3H]HETE-containing PtdOH (0.4% of the total PtdOH) in
      resting conditions. Upon mitogenic stimulation by Con A, the phorbol ester
      tetradecanoylphorbol acetate or the anti-CD3 mAb OKT3, this proportion was
      decreased to 0.1-0.2%, since the total PtdOH mass was more drastically increased
      than the 12-HETE-containing PtdOH species. Although present in relatively low
      amount in stimulated cells, 12-HETE-containing PtdOH species might have been
      generated in strategic compartments of the membrane bilayer so that the following
      events involved in the transduction of the mitogenic signal could be impaired. GC
      analyses have pointed out drastic variations in the fatty acid composition of
      PtdOH in non-enriched and in 12-HETE-enriched stimulated cells. Especially PtdOH
      synthesized in 12-HETE-enriched cells upon Con A stimulation contained a higher
      amount of saturated fatty acids and a lower amount of arachidonic acid than that
      formed in control cells stimulated with Con A alone. Such saturated PtdOH species
      with a low arachidonic acid content are very likely to have a low mitogenic
      potential.

PMID- 8521859
TI  - Characterisation of clusters of alpha-tocopherol in gel and fluid phases of
      dipalmitoylglycerophosphocholine.
AB  - The effect of alpha-tocopherol on the phase behaviour of aqueous dispersions of
      dipalmitoylglycerophosphocholine has been examined by differential scanning
      calorimetry, freeze-fracture electron microscopy, and real-time X-ray diffraction
      methods. The presence of alpha-tocopherol in proportions 2.5, 5, 7.5, and 10
      mol/100 mol results in a progressive decrease in the temperature of the gel to
      liquid-crystalline phase transition from 41.5 degrees C to 36 degrees C and a
      reduction in transition enthalpy from 35 kJ.mol-1 to 15 kJ.mol-1 phospholipid.
      The thermal data indicated that the pretransition of the phospholipid is
      eliminated even in mixtures containing 2.5 mol/100 mol alpha-tocopherol. Real
      time X-ray diffraction measurements using synchrotron radiation performed under
      identical conditions to the thermal studies showed clear transition sequences of
      L beta-->P beta-->L alpha for all mixtures. The sequence was reversible with
      hysteresis of 2-3 degrees C on cooling. Low-angle X-ray scattering from mixtures
      in the gel phase showed three lamellar repeat spacings of 6.35, 7.5, and 8.4 nm.
      The spacing at 6.35 nm was assigned to pure phospholipid from which alpha
      tocopherol has been phase separated into enriched domains giving lamellar repeat
      spacings of 7.5 nm and 8.4 nm. Low-angle diffraction patterns of mixtures in the
      fluid phase were characterised by two lamellar repeat spacings. The longer
      spacing of about 6.6 nm was assigned to pure phospholipid and the shorter spacing
      at about 6.1 nm to an alpha-tocopherol-enriched phase. Electron microscopy of
      freeze-fracture replicas of mixtures of phospholipid containing 10 mol/100 mol
      alpha-tocopherol thermally quenched from 10 degrees C and 60 degrees C, showed
      evidence of domain structures within the bilayer plane that appeared to be
      correlated between successive bilayers in multilamellar dispersions. Calculations
      of the stoichiometry of phospholipid: alpha-tocopherol in the alpha-tocopherol
      enriched domains based on enthalpy data and integrated X-ray scattering intensity
      gave values of 9.6:1 for the fluid phase and 9.2:1 for the gel phase. This was
      consistent with a clustering of alpha-tocopherol molecules in both gel and liquid
      crystal phases of dipalmitoyl-glycerophospholcholine in approximately the same
      stoichiometry.

PMID- 8521860
TI  - A glycoprotein inhibitor of pectin methylesterase in kiwi fruit. Purification by
      affinity chromatography and evidence of a ripening-related precursor.
AB  - The pectin methylesterase inhibitor from kiwi fruit (Actinidia chinensis) was
      purified by a single-step procedure based on affinity chromatography. Partially
      purified tomato pectin methylesterase was covalently bound to Sepharose. The
      affinity resin strongly and selectively binds the inhibitor, which could be
      eluted in high yield as a single, homogeneous and sharp peak by high salt
      concentration at pH 9.5 without loss of inhibitory activity. The purified protein
      possesses a molecular mass of 18 kDa, as estimated by SDS/PAGE, whereas by gel
      filtration under native conditions, its molecular mass appears to be 25 kDa. The
      inhibitor interacts with pectin methylesterase, forming a 1:1 complex, as
      demonstrated by gel-filtration experiments. The inhibitor was glycosylated. Its
      glycidic portion can be removed by digestion with N-glycosidase F after protein
      denaturation and, to a minor extent, by digestion with N-glycosidase H. No
      glycidic residue could be removed by digesting the native protein with those N
      glycosidases. Antibodies against pectin methylesterase inhibitor were raised in
      rabbits and used to evidence protein expression during fruit ripening. The
      results showed that the inhibitor is present in the unripe fruit as an inactive
      precursor with a higher molecular mass (30 kDa) and is transformed into the
      active protein, most likely by proteinase action, during the course of the
      ripening process.

PMID- 8521861
TI  - Peroxidative interaction of myoglobin and myosin.
AB  - Met-myoglobin [Fe(III)] was found to induce myosin cross-linking in the presence
      of H2O2 [Bhoite-Solomon, V. & Shaklai, N. (1992) Biochem. Int. 26, 181-189]. To
      assess the relevance of these findings to cellular pathology, peroxidation of
      myosin was performed with physiological divalent iron [Fe(II)] myoglobins in the
      oxy and deoxy forms. Both myoglobin forms were capable of mediating cross-linking
      of myosin. Deoxymyoglobin reactivity was similar to that of met-myoglobin, but
      the reactivity of oxymyoglobin was retarded compared to deoxymyoglobin. Cross
      linking of myosin occurred under a low flow rate of H2O2 (3 microM/min) and in
      the presence of excess oxymyoglobin over H2O2, known to diminish the steady state
      of the myoglobin active heme [ferryl, Fe(IV)]state. The adenosinetriphosphatase
      activity of myosin was reduced to about half due to cross-linking. Addition of
      myoglobin/H2O2 to high myosin concentrations (> = 20 microM) turned the solutions
      into gels, a phenomenon explained by the further formation of intermolecular
      super cross-links of soluble myosin. Thus, at cellular ionic strength in which
      myosin is insoluble, cross-linking of myosin could still be triggered by
      myoglobin and H2O2. Based on these data, it is suggested that myoglobin-induced
      cross-linking of myosin and the consequent loss of adenosinetriphosphatase
      activity may be involved in muscle malfunction under hypoxia when cellular
      peroxidants increase and the deoxymyoglobin form prevails.

PMID- 8521862
TI  - Identification of the iron-sulfur clusters in a ferredoxin from the archaeon
      Sulfolobus acidocaldarius. Evidence for a reduced [3Fe-4S] cluster with pH
      dependent electronic properties.
AB  - A ferredoxin isolated from the archaeon Sulfolobus acidocaldarius strain DSM 639
      has been shown to contain one [3Fe-4S]1 + 10 cluster with a reduction potential
      of -275 mV and one [4Fe-4S]2+/1+ cluster with a reduction potential of -529 mV at
      pH 6.4, in the temperature range 0-50 degrees C. The monomer molecular mass was
      confirmed to be 10907.5 +/- 1.0 Da by electrospray mass spectrometry, as
      calculated from the published amino acid sequence [Minami, Y. Wakabayashi. S.,
      Wada, K., Matsubara, H., Kerscher, L. & Oesterhelt, D. (1985) J. Biochem. (Tokyo)
      97, 745-751], while the holoprotein molecular mass was found to be 11,550 +/- 1.0
      Da. The reduced [3Fe-4S]0 cluster was also shown by direct electrochemistry and
      magnetic circular dichroic spectroscopy to undergo a one-proton uptake reaction
      as first observed for Azotobacter chroococcum ferredoxin I [George, S. J.,
      Richards, A. J. M., Thomson, A. J. & Yates, M. G. (1984) Biochem. J. 224, 247
      251]. The pKa of the protonation step has been determined by a novel thin film
      electrochemical method to be 5.8. This is significantly different from the pKa of
      7.7 determined for A. vinelandii ferredoxin I [Shen, B., Martin, L. L., Butt, J.
      N., Armstrong, F. A., Stout, C. D., Jensen, J. M., Stephens, P. J., LaMar, G. N.,
      Gorst, C. M. & Burgess, B. K. (1993) J. Biol. Chem. 268, 25928-25939] and
      indicates that the polypeptide chain around the [3Fe-4S] cluster controls this
      reaction. Although this appears to be only the second reported case of
      protonation at or near the reduced [3Fe-4S]0 cluster, its observation in S.
      acidocaldarius ferredoxin raises the question of the generality of this chemistry
      for 3Fe clusters. The similarity of the pKa to the estimated intracellular pH of
      S. acidocaldarius strongly suggests a physiological role for this process.

PMID- 8521863
TI  - UDP galactose:ceramide galactosyltransferase and glutamate/aspartate transporter.
      Copurification, separation and characterization of the two glycoproteins.
AB  - The oligodendrocyte-specific UDP-galactose:ceramide galactosyltransferase (CGT)
      is the key enzyme involved in the biosynthesis of the oligodendrocyte- and myelin
      specific cerebrosides. The galactosyltransferase was isolated and purified to
      homogeneity from Triton-X-100-solubilized rat brain microsomes by ion exchange,
      dye ligand and lectin affinity chromatography as a 64-kDa protein homogenous in
      SDS/PAGE. It copurified with the brain-specific Na(+)-dependent high-affinity L
      glutamate/aspartate neurotransmitter transporter (GLAST-1) of the central nervous
      system. Differential lentil lectin affinity chromatography led to the separation
      of two glycoproteins with very similar physical properties. CGT was identified as
      a high-mannose glycoprotein and GLAST-1 as a hybrid glycoprotein, both with a
      molecular mass of 64 kDa. Deglycosylation reduced the molecular mass of the two
      proteins to 59 kDa. A 70-kDa isoform of GLAST-1 was isolated from whole brain by
      wheat germ lectin affinity chromatography. Deglycosylation again reduced the
      molecular mass to 59 kDa. Therefore the 70-kDa isoform differs only in the degree
      of glycosylation from the 64-kDa GLAST-1 isoform. The two isoproteins form
      homodimers of 130 and 140 kDa, respectively. They were isolated and characterized
      with protein-chemical and immunological methods. Oligonucleotides derived from
      respective peptide sequences of CGT and GLAST-1 were successfully applied to the
      cloning of CGT and the first high-affinity glutamate neurotransmitter transporter
      (GLAST-1) in glia of the central nervous system as well.

PMID- 8521864
TI  - Purification of crotonyl-CoA reductase from Streptomyces collinus and cloning,
      sequencing and expression of the corresponding gene in Escherichia coli.
AB  - A crotonyl-CoA reductase (EC 1.3.1.38, acyl-CoA:NADP+ trans-2-oxidoreductase)
      catalyzing the conversion of crotonyl-CoA to butyryl-CoA has been purified and
      characterized from Streptomyces collinus. This enzyme, a dimer with subunits of
      identical mass (48 kDa), exhibits a Km = 18 microM for crotonyl-CoA and 15 microM
      for NADPH. The enzyme was unable to catalyze the reduction of any other enoyl-CoA
      thioesters or to utilize NADH as an electron donor. A highly effective inhibition
      by straight-chain fatty acids (Ki = 9.5 microM for palmitoyl-CoA) compared with
      branched-chain fatty acids (Ki > 400 microM for isopalmitoyl-CoA) was observed.
      All of these properties are consistent with a proposed role of the enzyme in
      providing butyryl-CoA as a starter unit for straight-chain fatty acid
      biosynthesis. The crotonyl-CoA reductase gene was cloned in Escherichia coli.
      This gene, with a proposed designation of ccr, is encoded in a 1344-bp open
      reading frame which predicts a primary translation product of 448 amino acids
      with a calculated molecular mass of 49.4 kDa. Several dispersed regions of highly
      significant sequence similarity were noted between the deduced amino acid
      sequence and various alcohol dehydrogenases and fatty acid synthases, including
      one region that contains a putative NADPH binding site. The ccr gene product was
      expressed in E. coli and the induced crotonyl-CoA reductase was purified tenfold
      and shown to have similar steady-state kinetics and electrophoretic mobility on
      sodium dodecyl sulfate/polyacrylamide to the native protein.

PMID- 8521865
TI  - Phosphorylation of the N-terminal intracellular tail of sucrase-isomaltase by
      cAMP-dependent protein kinase.
AB  - This paper reports the phosphorylation of the intracellular N-terminal tail of
      sucrase-isomaltase by protein kinase A and shows that this phosphorylation is
      targeted to Ser6 within a sequence Arg/Lys/Lys-Phe-Ser, which is conserved in all
      sucrase-isomaltase sequences known so far. By dephosphorylation of native sucrase
      isomaltase with an immobilized acid phosphatase and rephosphorylation with
      protein kinase A, it is shown that Ser6 may be partially phosphorylated in vivo,
      raising the possibility that the tail itself and its phosphorylation by protein
      kinase A may be physiologically significant.

PMID- 8521866
TI  - The influence of energy sources on the proteolysis of a recombinant
      staphylococcal protein A in Escherichia coli.
AB  - The kinetics of proteolysis of a recombinant staphylococcal protein A in
      Escherichia coli were studied by a Western-blotting-based method. The proteolysis
      constants obtained from this method are very close to those obtained from the
      traditional radioactive pulse-chase technique. Protein A was selectively degraded
      to a great extent, while host proteins were quite stable after heat induction of
      protein A expression. The proteolysis of protein A was much faster in the
      presence of energy sources compared to when cells were starved of energy. The
      degradation rate constants are 2.8 h-1 in the presence of 10 g/l glucose and
      about 0.4 h-1 in the absence of any external carbon source. The supplementation
      of glucose to the medium at 0-100 mg/l caused a gradual increase of proteolysis
      of protein A, but the proteolysis was saturated when the concentration of glucose
      exceeded 200 mg/l at a cell concentration of about 0.36 g/l. The respiration
      inhibitor sodium azide completely inhibited the degradation of protein A in
      glucose-free salt medium but had almost no effect in the presence of glucose.
      Therefore, the proteolysis process is energy dependent but the energy supply rate
      obtained by fermentation of glucose is enough to meet this requirement. The
      proteolysis rate increased with the temperature in the interval 5-45 degrees C
      but was then reduced due to damage of the proteolysis system by high temperature.
      At 60 degrees C, the proteolysis ceased completely within 30 min.

PMID- 8521867
TI  - The basic isoform of profilin in pathogenic Entamoeba histolytica. cDNA cloning,
      heterologous expression, and actin-binding properties.
AB  - In the human parasite Entamoeba histolytica, components of the cytoskeleton are
      involved in the pathogenicity by their contribution to immune evasion by antibody
      capping and shedding. In this study, we focus on profilin as a central regulatory
      component of the cytoskeleton. Profilin was isolated from trophozoites of the
      pathogenic E. histolytica strain SFL-3, and partial amino acid sequences were
      used to devise a probe for isolating a profilin cDNA. The deduced complete
      primary structure was divergent: plant profilins with amino acid sequence
      identities in the range 33-38% were more closely related than the mammalian
      profilins with sequence identities 21-28%. The cDNA was expressed as a nonfusion
      protein in Escherichia coli. Isoelectric focussing of the natural profilin
      isolated from E. histolytica showed two isoforms with different isoelectric
      points; the recombinant profilin migrated with the basic isoform. In a blot
      overlay experiment, purified 125I-labeled recombinant profilin bound not only to
      plant actin, but also to mammalian actin, demonstrating that cytoskeletal
      components from distantly related organisms with divergent primary structures can
      be compatible.

PMID- 8521868
TI  - Facilitation of gap-junctional communication and gap-junction formation in
      mammalian cells by inhibition of glycosylation.
AB  - The effect of inhibition of glycosylation on basal and cAMP-induced homologous
      and heterologous gap-junctional communication was studied in various normal and
      transformed cell lines that express mRNA and protein for the gap-junction-forming
      gene, connexin43. In communication-incompetent Morris hepatoma cells, inhibition
      of glycosylation alone did not induce junctional communication, but enhanced cAMP
      induced junctional communication severalfold. This enhancement correlated with
      the presence of more gap junctions at the membrane appositions, but not with an
      increase in connexin43 mRNA or protein in these cells. In several other normal
      and transformed cell lines, inhibition of glycosylation enhanced both basal as
      well as cAMP-induced junctional communication. Furthermore, both basal and cAMP
      induced heterologous junctional communication between nontransformed RL-CL9 and
      several other nontransformed and transformed cells was also enhanced when
      glycosylation was inhibited. Our data suggest that the formation of gap junctions
      between cells of the same type or different types is subject to local constraints
      imposed by the oligosaccharide moieties of the glycoproteins of the plasma
      membranes of the gap-junction-forming cells and that inhibition of glycosylation
      abrogates such constraints. Our findings thus suggest a new basis for the
      communication deficiency observed in several types of transformed cells and
      between transformed and normal cells.

PMID- 8521869
TI  - Rab3a, a small GTP-binding protein, undergoes fast anterograde transport but not
      retrograde transport in neurons.
AB  - Rab3a is a small GTP-binding protein that is associated with synaptic vesicles in
      neurons and that undergoes membrane dissociation-association paralleling the
      synaptic membrane cycle. Using the sciatic nerve as a model, we have studied the
      axonal transport of Rab3a by quantitative immunocytochemistry and immunoblotting
      and electron microscopy. Ligation of the sciatic nerve resulted in a progressive
      accumulation of Rab3a proximal of the ligation site in virtually all axons with
      an onset of less than 1 h. Accumulation of Rab3a was accompanied by accumulation
      of synaptophysin and synapsin I, two synaptic vesicle membrane proteins, and
      accumulation of clathrin light chain. Immunogold electron microscopy revealed
      that organelles labeled for Rab3a were mainly small round vesicles with an
      average diameter of 50 to 60 nm, indistinguishable from those labeled for the
      synaptic vesicle protein synaptophsin. In contrast, no retrograde accumulation of
      Rab3a was observed in most axons, with sparse labeling being confined to few thin
      axons. For other synaptic vesicle membrane proteins as well as for clathrin light
      chain, substantial accumulations were observed on the distal side of the
      ligation. We conclude that Rab3a associates with synaptic vesicle precursors in
      the cell soma before entering the axon and being transported to the synapse. At
      the end of its useful life-span, however, Rab3a does not associate with
      retrogradely transported membrane material, suggesting that it is degraded within
      the nerve terminal.

PMID- 8521870
TI  - Cysteine proteinases in GH4C1 cells, a rat pituitary tumor cell line, are
      secreted by the constitutive and regulated secretory pathways.
AB  - Secretory granules of GH4C1 cells, a rat pituitary tumor cell line, are known to
      be induced by the treatment of estradiol (E2), insulin, and epidermal growth
      factor (EGF). We examined changes in the localization of cathepsins B, H, and L,
      lysosomal cysteine proteinases, in GH4C1 cells before and after hormonal
      treatment. Northern blotting and immunofluorescence microscopy showed that both
      mRNAs and intracellular protein concentrations of these enzymes were increased in
      the hormone-induced cells. By immunoelectron microscopy, immunogold particles
      indicating cathepsins B, H, and L were localized not only in lysosomes but also
      in some secretory granules. To further examine the molecular forms of these
      proteinases in secretory granules, radiolabeling and immunoprecipitation methods
      were applied to the media of the cells incubated with or without secretagogues
      (100 nM 12-O-tetradecanoylphorbol-13-acetate and 50 microM forskolin); the
      proforms of cathepsins B, H, and L were secreted from the cells by the
      constitutive pathway, whereas the mature forms of cathepsins B and H, and the
      proform and mature form of cathepsin L were secreted by the regulated pathway.
      These results suggest that in hormone-induced GH4C1 cells, cathepsins B, H, and L
      are sorted from the Golgi complex not only into lysosomes but also into secretory
      granules, in which proforms of cathepsins B and H, and a part of procathepsin L
      are processed into mature forms.

PMID- 8521871
TI  - Immunolocalization of a 43 kDa peroxisomal membrane protein in the liver of
      patients with generalized peroxisomal disorders.
AB  - The presence of peroxisomal membrane ghosts was examined in liver biopsies from
      eleven patients presenting the clinical and biochemical picture of a generalized
      peroxisomal disorder (Zellweger syndrome, neonatal adrenoleukodystrophy,
      infantile Refsum disease and variants of these syndromes). A polyclonal antibody
      raised against the membrane of human liver peroxisomes and recognizing a 43 kDa
      peroxisomal membrane protein (PMP) was used. In human control liver the
      antibodies react in a distinct and specific way with the peroxisomal membrane.
      Two types of organelles with an immunoreactive membrane were identified in the
      liver parenchymal cells of the patients: organelles containing an electron-dense
      core and organelles with electron transparent contents. Both types may co-occur
      in the same patient; in two patients they were found in the same cell. The
      organelles are rare, and their number varies between patients. The first type
      possibly corresponds to the previous morphological description of aberrant
      peroxisomes in the liver of patients with Zellweger syndrome, neonatal
      adrenoleukodystrophy and infantile Refsum disease. The empty looking organelles
      have not been reported previously in the liver, some of the "empty" organelles
      seem to be enclosed by a double membrane. Morphometrical analysis in three
      patients indicated that both types of organelles (corrected mean d-circle 0.271
      0.306 micron for the "empty" and the dense core organelles, respectively) are
      smaller than the peroxisomes in postnatal control liver and in fetal liver. In
      one patient (infantile Refsum disease) immunoreactive organelles were not
      detected. The organelles with the electron-dense core were not found in two
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521872
TI  - Abnormal A-type lamin organization in a human lung carcinoma cell line.
AB  - We have studied the expression of lamins A and C (A-type lamins) in a lung
      carcinoma cell line using type-specific monoclonal antibodies. Using
      immunofluorescence and immunoblotting studies it was noted that several
      irregularities in lamin expression exist in the cell line GLC-A1, derived from an
      adenocarcinoma. First, the expression of the A-type lamins was lower than in
      other adenocarcinoma cell lines of the lung. Also the ratio between lamins A and
      C proteins was 1:8 instead of the 1:1 ratio seen in the other cell lines.
      Northern blotting confirmed the altered level of A-type lamin expression.
      Secondly, an abnormal localization of lamin A was observed. Intensely fluorescing
      lamin A aggregates were observed in the nucleus, rather than the typical
      perinuclear staining pattern. Confocal scanning laser microscopy revealed that
      the lamin A aggregates were indeed present throughout the internal nucleus. When
      these cells were extracted with Triton X-100 the nucleoplasmic aggregates
      disappeared, which indicates that the A-type lamins are not properly incorporated
      into the lamina. The A-type lamins in other cell lines derived from
      adenocarcinomas remained present in the nuclear periphery after extraction with
      the non-ionic detergent. Immunoblotting studies of the Triton X-100 soluble and
      insoluble fractions showed that lamin A and an apparently truncated product,
      which was detected with the lamin A antibody, were present in the insoluble
      fraction of GLC-A1. This truncated product is partly Triton X-100 soluble since
      it was also detected in the detergent soluble fraction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8521873
TI  - Phosphatidylserine exposure on the platelet plasma membrane during A23187-induced
      activation is independent of cytoskeleton reorganization.
AB  - Modifications in cytoskeleton organization (monitored by scanning electron
      microscopy study of platelet shape) and cytoskeleton proteolysis were
      investigated for their role in phosphatidylserine exposure (measured with spin
      labeled analogues of phospholipids) during A23187-induced activation of human
      platelets. Resting platelets treated with combinations of calpeptin and
      cytoskeleton-disrupting agents (nocodazole or cytochalasin D) remained discoid,
      and there was no dense granule release, cytoskeleton proteolysis or vesicle
      shedding. Spin-labeled phosphatidylserine was fully and rapidly redistributed
      (t1/2 approximately 5 min) from the outer to the inner leaflet of the plasma
      membrane through ATP-dependent aminophospholipid translocase activity. In
      contrast, spin-labeled phosphatidylcholine was only partially and slowly
      redistributed (less than 20% within 60 min) to the inner leaflet. Filopod
      formation, vesicle shedding, and calpain-mediated proteolysis were inhibited
      during activation of platelets treated with calpeptin and cytoskeleton-disrupting
      agents. Moreover, regardless of whether platelets were treated or not, spin
      labeled phosphatidylserine was rapidly (t1/2 < 1 min) and massively (50%) exposed
      on the outer leaflet of the plasma membrane, while the slow and slight spin
      labeled phosphatidylcholine influx did not counterbalance spin-labeled
      phosphatidylserine outflux. These results demonstrated that phosphatidylserine
      exposure was not connected to the following activation-related processes:
      cytoskeleton modifications (actin and tubulin polymerization, submembrane
      skeleton proteolysis), inhibition of aminophospholipid translocase, and filopod
      formation. Moreover, the redistribution kinetics of spin-labeled phospholipids
      during activation strongly suggested the involvement of an aminophospholipid
      exposure mechanism that differs from a scrambling phenomenon.

PMID- 8521874
TI  - A massive new posttranslational modification occurs on axonemal tubulin at the
      final step of spermatogenesis in Drosophila.
AB  - Using two antibodies raised against Paramecium axonemal tubulin, a monoclonal
      antibody, AXO 49 (Callen et al., Biol. Cell 81, 95-119 (1994)), and a polyclonal
      antibody, PAT (Cohen et al., Biol. Cell 44, 35-44 (1982)), which have been shown
      elsewhere to detect a new posttranslational modification of tubulin presumably
      corresponding to polyglycylation, we have analyzed the occurrence of this
      modification during spermatogenesis in Drosophila. Results obtained by
      immunofluorescence on cysts isolated by laceration of testes showed that the
      antibodies reacted on axonemal microtubules of several species within the genus.
      Observation of different stages of differentiation of D. obscura sperm cells
      indicated, first, that the epitopes reactive with both antibodies appeared at
      late stages, and secondly, that they were detected simultaneously along all
      axonemes within a cyst. Immunofluorescence on semithin sections and electron
      microscopic immunocytochemistry on ultrathin sections confirmed that the
      appearance of the epitope recognized by the monoclonal antibody occurred at the
      time of the individualization process of spermatids in D. melanogaster. These
      results indicate that the posttranslational modification occurs as a very late
      event, after complete assembly of axonemal microtubules, and that the axonemal
      tubulin becomes modified when axonemal microtubules become coupled with the
      membrane, suggesting that the modification may in some way be induced by the
      microtubule-membrane interaction.

PMID- 8521875
TI  - Ca(2+)-dependent polarization of axis establishment in the tip-growing organism,
      Saprolegnia ferax, by gradients of the ionophore A23187.
AB  - A gradient of the divalent cation ionophore A23187 polarized axis establishment
      in regenerating hyphal protoplasts and germinating cysts of the tip-growing
      oomycete Saprolegnia ferax. An average of sixty-three percent of new hyphae
      emerging from initially spherical protoplasts were oriented towards the ionophore
      source. This polarization was dependent on the presence of Ca2+ and could not be
      elicited by the presence of either 1 mM Mn2+ or Mg2+. A similar but less marked
      (56%) orientation was shown by germinating cysts, either with or without
      pretreatment with the anti-microtubule drug, nocodazole. Further, cyst-derived
      hyphae which did not originally emerge facing the ionophore source later showed a
      tendency to reorient their growth towards it. Since A23187 is known to facilitate
      the entry of Ca2+ into cells, and since, in protoplasts at least, the response is
      Ca2+ dependent, these results imply that an ionophore-generated Ca2+ gradient
      within the cells may be responsible for the observed polarizing influence on
      protoplasts and cysts. It is likely that the role of Ca2+ is essentially the same
      in both systems: a primary common factor in the establishment of the growth axis.
      The results provide evidence that Ca2+ polarizes hyphal growth and support the
      idea that Ca2+ has a ubiquitous, primary role in the initiation of polarity in
      tip-growing cells.

PMID- 8521876
TI  - Free calcium in Micrasterias: local gradients are not detected in growing lobes.
AB  - Intracellular free Ca2+ ([Ca2+]) has been measured in growing unicells of two
      species of the green alga, Micrasterias, which have been injected with the
      indicator dye fura-2-dextran. Ratiometric imaging of Micrasterias denticulata
      yields levels of 170 to 200 nM [Ca2+] but fails to reveal a significant [Ca2+]
      gradient associated with the tips of growing lobes, or in any other region of the
      cell. In Micrasterias muricata slight elevations from a basal value of 350 to 500
      nM have been observed, but these might be due to a general inward leakage of Ca2+
      at the plasma membrane which is enhanced at the narrow lobes of this cell because
      of their greater relative surface to volume ratio. Experimental perturbation of
      the intracellular [Ca2+] with injection of the ion or the addition of the non
      fluorescent ionophore, Br-A23187, reveal that [Ca2+] elevations can be generated
      and indicate that if they naturally occurred, the image system would have
      detected them. Further evidence that [Ca2+] gradients are lacking derives from
      studies with BAPTA-type buffers. Injection of 5,5'-dibromo BAPTA and 4,4'
      difluoro BAPTA, which in several other systems are the most effective at
      dissipating intracellular [Ca2+] gradients, have no effect on development of
      Micrasterias. Taken together, these studies indicate that lobe outgrowth in
      Micrasterias does not occur in association with marked localized [Ca2+]
      gradients.

PMID- 8521877
TI  - Effects of calcium channel blockers on NIH 3T3 fibroblasts expressing the Ha-ras
      oncogene.
AB  - NIH 3T3 fibroblasts expressing the ras oncogene (+ras cells) respond to
      bradykinin, bombesin or serum with sustained oscillations of cell membrane
      potential reflecting oscillations of intracellular calcium activity and
      subsequent activation of calcium-sensitive K+ channels. In contrast, identical
      cells not expressing the oncogene (-ras cells) respond to bradykinin with a
      single, transient hyperpolarization of the cell membrane. Furthermore, +ras cells
      are characterized by a serum-independent proliferation, an increase in cell
      volume and a marked reorganization of the cytoskeleton. It has been shown
      previously that the calcium channel blocker nifedipine, but not verapamil and
      diltiazem, inhibits oscillations of cell membrane potential as well as
      proliferation. In this study, we have examined the effect of several calcium
      channel blockers (bepridil, nifedipine, verapamil, diltiazem) on the
      proliferation, volume and cytoskeletal reorganization of +ras cells. Bepridil (10
      mumol/l), which is also shown here to inhibit oscillations of cell membrane
      potential, and nifedipine (10 mumol/l) caused a decrease in cell number, whereas
      verapamil and diltiazem (10 mumol/l each) resulted in growth rates which did not
      differ from untreated +ras cells. The increase in cell volume as observed in
      untreated +ras cells was also observed for cells treated with verapamil and
      diltiazem, whereas cell volumes of +ras cells treated with bepridil and
      nifedipine were markedly reduced and similar to the values obtained for -ras
      cells. In addition, bepridil and nifedipine markedly inhibited cytoskeletal
      rearrangement, i.e depolymerization of actin-containing stress fibers. This
      inhibitory effect was not observed for verapamil and diltiazem.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8521878
TI  - Potentiating effects of clofibric acid on the differentiation of HL-60 human
      promyelocytic leukemia cells induced by retinoids.
AB  - Retinoids induce granulocytic differentiation of HL-60 human promyelocytic
      leukemia cells. In this study we demonstrate that clofibric acid, a well known
      peroxisome proliferator in rodent, augments the differentiation caused by 0.01
      microM and 0.1 microM all-trans retinoic acid, and by 0.3 and 3 microM all-trans
      retinol. Clofibric acid alone has only marginal effects on the myeloid
      differentiation, whereas clofibric acid together with the glucocorticoid analogue
      dexamethasone gives a larger effect. Exposure of cultures to retinoid inhibits
      the growth of the cells, but despite the increased differentiation addition of
      clofibric acid to the medium does not further inhibit the growth. HL-60 cells
      express the nuclear receptor NUCI, a human receptor related to the peroxisome
      proliferator activated receptor (PPAR).

PMID- 8521879
TI  - Digitalis--friend or foe?
AB  - The therapeutic efficacy of cardiac glycosides is not widely appreciated either
      in respect of their positive inotropic value or antiarrhythmic activity. Although
      cardiac glycosides do not prevent an increase in ventricular rates during
      exercise they do slow the heart rate at rest in patients with atrial
      fibrillation. The clinical importance of the potentially beneficial influence of
      the digitalis glycosides on the negative force-frequency relationship (Bowditch
      effect), preload-force relationship (Frank-Starling's Law) and baroreceptor
      dysfunction in heart failure await clarification. In patients with heart failure,
      the positive inotropic effects of the digitalis glycosides are mild, but show no
      tolerance during prolonged administration. Digitalis glycosides are the only
      group of positive inotropic drugs that persistently increase the ejection
      fraction during long-term administration in patients with heart failure. These
      haemodynamic benefits are translated into decreased symptoms and increased
      exercise capacity in patients with congestive heart failure. Although their
      clinical efficacy in the different stages of heart failure remains undefined,
      recent evidence indicates that their therapeutic benefit is on a par with
      diuretics and ACE inhibitors in symptomatic heart failure. Results of studies
      specifically directed to determining the impact of the cardiac glycosides on
      prognosis are awaited.

PMID- 8521880
TI  - Heart failure syndrome. Rationale for current drug treatment.
AB  - In the initial phase of heart failure, cardiac output and pressure are maintained
      by increasing sympathetic drive and by cell hypertrophy. Elevated end-diastolic
      volume, a reduced ejection fraction and a higher filling pressure also occur.
      Only in more severe heart failure, when cardiac output cannot be maintained, do
      symptoms appear which may vary between congestion, exercise intolerance, left
      ventricular dysfunction, arrhythmias or a combination of each. Drug treatment has
      principally two aims: first, to improve symptoms, second, to influence prognosis,
      which is very poor in advanced heart failure. Symptom improvement will also
      depend on whether the condition is acute, subacute or chronic heart failure. In
      the acute situation diuretics are normally the first choice of treatment, whereas
      in chronic heart failure the ACE inhibitors have proved themselves to be the
      drugs which most improve prognosis. The role of digitalis, still frequently used,
      remains unclear, and its importance will be revealed when the results of ongoing
      studies are announced.

PMID- 8521881
TI  - Improvement in cardiac myocyte function by biological effects of medical therapy:
      a new concept in the treatment of heart failure.
AB  - Virtually all medications used to treat cardiac problems act through a
      pharmacological mechanism that immediately improves electrical or mechanical
      function or inhibits the manifestation of a pathological process. The idea that
      medical therapy could exert a favourable myocardial effect by fundamentally
      improving the biological function of cardiac myocytes is novel, and is based on
      the observation that in heart failure the acute pharmacological effects of beta
      blocking agents on left ventricular function are completely different from their
      long-term effects. beta-blocking agents improve intrinsic systolic function long
      term, despite depressing function initially through the pharmacological effect of
      withdrawing adrenergic drive, indicating that the beneficial effect of this form
      of therapy is due to improved myocyte biology. Implicit in this observation is
      that improvement in the fundamental biology of failing cardiac myocytes should
      favourably affect the natural history of heart failure.

PMID- 8521882
TI  - Vasodilating beta-blockers in heart failure.
AB  - Carvedilol is a non-selective beta-adrenoceptor antagonist with vasodilating
      properties which has been shown to be effective in the management both of
      hypertension and of stable angina pectoris. In order to explore its wider
      efficacy in patients with manifest heart failure, a preliminary study was
      performed in patients with chronic stable angina pectoris accompanied by abnormal
      left ventricular wall motion, but without overt heart failure (mean ejection
      fraction < 40%). Six patients were given carvedilol 25 mg b.i.d. for 2 weeks
      followed by 50 mg b.i.d. for a further 2 weeks according to a single-blind
      placebo-controlled protocol. At the end of the 4 week period of treatment, in
      four patients left ventricular wall motion was improved, in two it was unchanged,
      and in none was there any deterioration; mean ejection fraction increased from 40
      to 48%. These results prompted a further study in 17 patients with chronic
      ischaemic heart failure. The haemodynamic and clinical responses to intravenous
      carvedilol followed by the oral drug (50 mg b.i.d.) for 8 weeks were studied.
      There was an improvement in all haemodynamic variables, although postural
      hypotension necessitated withdrawing two patients, and clinical deterioration was
      evident in two others. The beneficial effects of carvedilol were considered to be
      related to the combined reduction in afterload and inhibition of neurohumeral
      activation. These results have been confirmed in placebo-controlled, double-blind
      studies.

PMID- 8521883
TI  - Carvedilol, a novel multiple action antihypertensive agent with antioxidant
      activity and the potential for myocardial and vascular protection.
AB  - Carvedilol is a vasodilating, beta-adrenoceptor antagonist currently marketed for
      the treatment of mild to moderate hypertension. Carvedilol acts to reduce total
      peripheral resistance by blocking peripheral vascular alpha 1-adrenoceptors,
      thereby producing systemic arterial vasodilation, while at the same time
      inhibiting reflex tachycardia through the blockade of myocardial beta
      adrenoceptors. In addition to its established efficacy and safety as an
      antihypertensive agent, carvedilol has been shown to produce significant
      cardioprotection in experimental animal models of acute myocardial infarction,
      with the most dramatic effect being observed in the pig model of myocardial
      ischaemia and reperfusion, where the reduction in infarct size reached 91%.
      Recent pharmacological studies have revealed additional novel properties of
      carvedilol which may account for the marked protection produced by the drug in
      the ischaemic myocardium and which may also result in protection against other
      chronic pathological processes, such as atherosclerosis and acute vascular
      injuries. The latter arise from surgical procedures, such as percutaneous
      transluminal coronary angioplasty and coronary artery bypass grafting.
      Specifically, carvedilol, as well as some of its hydroxylated metabolites, are
      potent antioxidants. In physicochemical, biochemical and cellular assays,
      carvedilol and several of its metabolites prevent lipid peroxidation and the
      depletion of endogenous antioxidants, such as vitamin E and glutathione.
      Moreover, carvedilol and its metabolites prevent the oxidation of LDL to oxidized
      LDL, the latter being directly cytotoxic and known to activate
      monocytes/macrophages and to stimulate foam cell formation. In addition,
      carvedilol was found to inhibit both rat and human vascular smooth muscle cell
      proliferation and migration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521884
TI  - Evolution of the neurohormonal hypothesis to explain the progression of chronic
      heart failure.
AB  - During the last 20 years, physicians have generally regarded heart failure as a
      haemodynamic disorder in an attempt to explain patients' symptoms and disability.
      This model led to the widespread evaluation of peripheral vasodilators and the
      development of novel positive inotropic agents, but long-term use of these drugs
      failed to improve symptoms and was frequently accompanied by an increase in the
      risk of death. These clinical observations raised concerns about the validity of
      the haemodynamic hypothesis and led to the development of alternative models of
      heart failure--most importantly, the neurohormonal hypothesis. According to the
      neurohormonal model, heart failure develops and progresses because endogenous
      neurohormonal systems that are activated by the initial injury to the heart exert
      a deleterious effect on the circulation. Recognition of the importance of
      neurohormonal activation has led to the intense interest in the use of
      neurohormonal antagonists--converting--enzyme inhibitors and beta-adrenergic
      blockers--in the treatment of chronic heart failure. The results of randomized
      clinical trials with a variety of neurohormonal antagonists have been
      encouraging, and widespread acceptance of these drugs is expected to lead to
      clinical benefits for many patients.

PMID- 8521885
TI  - Refocus on diuretics in the treatment of heart failure.
AB  - Diuretics have long been accepted as the traditional first-line treatment of the
      patient with symptomatic heart failure whatever its aetiology or dysfunctional
      stage. Their acceptance in this role is based on the rapid improvement in
      congestive symptoms experienced by most patients, which is arguably greater than
      that induced by any other currently available anti-heart failure drug. This
      symptomatic efficacy and their universal clinical acceptance as first-step
      treatment for the patient with symptoms of heart failure has precluded formal
      examination of their impact on prognosis. Evidence from indirect studies suggests
      that when used alone they may not be able to prevent clinical deterioration,
      possibly due to excitation of the renin-angiotensin-aldosterone system. When such
      excitation is suppressed by concomitant administration of angiotensin-converting
      enzyme inhibitors, relief of congestive symptoms is enhanced and the morbidity
      and mortality risk of heart failure significantly reduced. Studies on the
      mechanisms of diuretic resistance have demonstrated the synergy of diuretic
      activity when low doses of diuretics acting at different sites of the nephron are
      used in combination. Diuretics remain the cornerstone of treatment for symptoms
      in congestive heart failure but their overall efficacy is substantially improved
      when combined with ACE inhibitors.

PMID- 8521886
TI  - 'Firm' versus 'soft' double pigtail ureteric stents: a randomised blind
      comparative trial.
AB  - It is generally considered that 'firm' double pigtail ureteric catheters, while
      easier to insert and less prone to migration, may cause more patient discomfort
      than the 'softer' variety of stent. Objective support for these perceptions is
      however lacking. The aim of this study was to compare firm and soft stents
      regarding their ease of insertion, positional stability, biocompatibility and
      patient tolerance. 155 patients were randomised to receive 'firm' (polyurethane,
      n = 78) or 'soft' (Sof-Flex, n = 77) stents. Ease and mode of insertion was
      recorded at time of initial placement. Positional stability, degree of bladder
      inflammation, stent encrustation and patient tolerance were recorded at the time
      of removal. Patient tolerance was assessed by symptom score in double-blind
      fashion. Results showed no significant difference in ease of insertion,
      positional stability, degree of bladder inflammation or stent encrustation
      between the two groups. There was a significantly higher incidence of dysuria,
      renal and suprapubic pain in the firm stent group. There was no significant
      difference in the incidence of urgency, frequency, nocturia or haematuria. Normal
      activity and return to work were reported in 67 and 45% of patients with soft and
      firm stents, respectively. The data indicates that patient tolerance appears to
      be related to the softness of the stent material.

PMID- 8521887
TI  - Determination of prostate gland volume by transrectal ultrasound: correlation
      with radical prostatectomy specimens.
AB  - Estimation of the prostate gland volume employing transrectal ultrasound provides
      important additional information in patients with benign and malignant diseases
      of the prostate. Twenty-five patients underwent transrectal ultrasound of the
      prostate prior to radical prostatectomy for organ-confined cancer of the
      prostate. The prostate gland volume was calculated employing two different
      methods. The prostate specimen weights were compared with the results of each of
      the volume estimation method. The prolate ellipse formula, widely used as an
      alternative to planimetry, demonstrated a correlation coefficient of r2 = 0.831.
      However, a variation of the prolate ellipse formula expressed as (width x width x
      height) x pi/6, which is easier to perform as described by Terris and Stamey,
      exhibited a correlation coefficient of r2 = 0.829. It appears to be a reliable
      means of estimating prostate gland volume, especially in cases in whom the
      original formula is difficult to apply.

PMID- 8521888
TI  - Diagnosis and follow-up of testicular carcinoma in situ by DNA image cytometry.
AB  - Carcinoma in situ (CIS) of the testis has been described as precursor of all
      types of germ cell cancer except spermatocytic seminoma. At present the diagnosis
      of CIS is based on light microscopic examination of a testis biopsy specimen. A
      series of 50 infertile patients underwent both surgical testis biopsy and
      aspiration biopsy as part of a study protocol in order to assess spermatogenesis.
      In 1 patient embryonal carcinoma and contralateral CIS was diagnosed, in 1
      patient bilateral CIS was discovered. Diagnosis of CIS was made by DNA image
      cytometry of the testis aspiration biopsy: a typical aneuploid cell population
      was shown consistent with malignancy. Follow-up was performed by repeated
      aspiration testis biopsies: DNA histograms showed complete absence of haploid
      cells consistent with Sertoli-cell-only syndrome in the patient with unilateral
      germ cell cancer and contralateral CIS treated with localized radiation. In the
      other patient no treatment was performed and DNA histograms continuously showed
      an aneuploid cell population consistent with persistent CIS. No invasive cancer
      developed within 4 years after diagnosis. Our results underline the potential use
      of DNA cytometry in the diagnosis and follow-up, of CIS of the testis offering
      the advantage of an objective and rapid technique.

PMID- 8521889
TI  - Extragonadal germ cell tumors: prognostic factors and long-term follow-up.
AB  - The records of 23 patients (22 male and 1 female, median age 28 years) with
      extragonadal germ cell tumors (EGCT) treated between 1974 and 1993 were reviewed
      retrospectively to investigate long-term survival and prognostic factors.
      Treatment consisted of cisplatin-based chemotherapy plus local irradiation or
      surgery. There were 7 seminomas, 5 poorly differentiated carcinomas (PDC) with
      elevated biomarkers, and 11 nonseminomatous germ cell tumors (NSGCT). The primary
      sites were retroperitoneum (10 cases), mediastinum (5 cases), pineal gland (4
      cases) and other (4 cases). Two partial and 14 complete responses (69.6% overall)
      were achieved with primary therapy. After a median follow-up of 63 months, 10
      (43.5%) patients live disease-free and 5-year survival is 55%. Seminomas showed
      an excellent outcome. Retroperitoneal NSGCT behaved like testicular neoplasms.
      Between nonseminoma patients, PDC histology and mediastinal primary were
      associated with the worst prognoses. EGCT patients should be treated and reported
      separately according to histology and primary site.

PMID- 8521890
TI  - Intratesticular effects of cisplatin-based chemotherapy.
AB  - The question is addressed whether cisplatin-based chemotherapy for germ cell
      cancer has the same efficacy in intratesticular and in extragonadal sites. For
      this purpose, 7 patients with germ cell cancer, aged 16-35 years were analysed.
      Four of the patients had palpable testicular tumors, 3 had occult testicular
      tumors. All presented with advanced disease and therefore received chemotherapy
      as the first step of treatment. Orchiectomy was done in the later course. A
      significant clinical response to chemotherapy was observed at the intratesticular
      tumor site as well as at extragonadal sites in all patients. Orchiectomy
      specimens contained viable cancerous cells in 2 patients after two courses of
      chemotherapy while in 5 patients no invasive germ cell cancer was found. Severe
      depression of germ cells was observed in all specimens. Testicular
      intraepithelial neoplasia (TIN; carcinoma in situ) persisted in 4 patients, 1 of
      whom also had viable cancerous cells in the specimen. Cisplatin-based
      chemotherapy is also active in intratesticular tumors but there seems to be a
      slightly different response of metastatic germ cell cancer and intratesticular
      tumor. Tumor heterogeneity appears to be the most important reason for this
      different response. The lower response of TIN to chemotherapy as compared to
      invasive testicular cancer is probably due to a genetically determined lower
      sensitivity. The blood-testis barrier might contribute a minor part to this
      phenomenon by modulating the intratubular concentrations of cytostatic compounds.
      The efficacy of cisplatin-based chemotherapy on invasive intratesticular tumors
      is not compromised by the blood-testis barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521892
TI  - Predictive value of a new scoring system for the outcome of primary in situ
      experimental extracorporeal shock wave lithotripsy of upper ureteral calculi.
AB  - The results of primary in situ extracorporeal shock wave lithotripsy of upper
      ureteral calculi were analyzed retrospectively in 491 eligible patients. The
      treatment was successful in 371 patients (76%). Degree of obstruction, stone
      size, localization of stone, history of previous ipsilateral surgery, and body
      mass index were found to be factors that can influence the outcome of treatment.
      A scoring system based on these factors has been developed to select the
      appropriate group of patients for primary in situ extracorporeal shock wave
      lithotripsy of upper ureteral calculi.

PMID- 8521891
TI  - A method of human semen centrifugation to minimize the iatrogenic sperm injuries
      caused by reactive oxygen species.
AB  - Current techniques of sperm preparation for in vitro fertilization or
      intrauterine insemination require centrifugation of human semen to separate
      spermatozoa from the seminal plasma. Centrifugation increases reactive oxygen
      species (ROS) formation in semen. Moreover, high levels of ROS are associated
      with sperm membrane injury through spontaneous lipid peroxidation, which may
      alter sperm function. We investigated the relationship between centrifugation
      variables (time and g-force) and ROS production to establish an optimal
      centrifugation protocol for sperm preparation techniques. Semen from 38 men (24
      patients and 14 normal volunteers) was evaluated for the formation of ROS before
      centrifugation and after centrifugation at 200 g for 2 or 10 min and after 500 g
      for 2 or 10 min. The absence of white blood cells in semen which can also produce
      ROS was determined with the myeloperoxidase technique (Endtz test). All specimens
      were negative (< 1 x 10(6)/ml) by the Endtz test. The formation of ROS was
      measured by chemiluminescence. ROS formation was regarded as high (positive) when
      the chemiluminescence response was at least 10 x 10(4) counted photons/min (cpm).
      The sperm concentration in each sample was adjusted to 15-20 x 10(6) cells/ml
      before analysis. Eight specimens (7 patients and 1 donor) exhibited high levels
      of ROS before centrifugation. All 8 showed further, significant increases in ROS
      formation regardless of g-force or time. The increase in ROS was significantly
      less when semen was centrifuged for 2 as compared to 10 min (p < 0.001). Six
      specimens previously ROS-negative became ROS-positive after centrifugation for 10
      min at 200 and 500g. We conclude that the time of centrifugation is more
      important than g-force for inducing ROS formation in semen. Based on these
      results, we recommend a shorter centrifugation period in the preparation of sperm
      for assisted reproductive techniques.

PMID- 8521894
TI  - Vacuum therapy combined with psychotherapy for management of severe erectile
      dysfunction.
AB  - We used vacuum therapy in combination with psychotherapy in 145 patients with
      different types of erectile dysfunction (ED). The age range was 24-82 years
      (average 53.4 +/- 2.7 years). The patients were divided into 3 groups according
      to the type of ED: 26.2% psychogenic, 36.5% organic, 37.2% mixed. All received
      the same treatment. Improvement in sexual function parameters, both subjective
      (adequate erection, spontaneous erection) and objective (penile brachial index,
      maximal rigidity of penis) were compared among the groups. The best results were
      noted in the psychogenic and organic ED patients. Of the 38 patients with
      psychogenic ED, 12 (31.5%) had coitus after treatment without any intervention,
      23 (60.5%) had coitus with help of the vacuum constriction device (VCD). Of 53
      patients with organic ED, 11 (20.7%) had coitus without any intervention, and 39
      (73.5%) had coitus with help of the VCD. Of the total study population (n = 145),
      31 (21.3%) had coitus without any intervention, 98 (67.5%) had coitus with help
      of the VCD. In 16 (11%) cases, there was no improvement in either subjective or
      objective parameters of sexual function.

PMID- 8521893
TI  - Extent of disease based on initial bone scan: important prognostic predictor for
      patients with metastatic prostatic cancer. Experience from the Scandinavian
      Prostatic Cancer Group Study No. 2 (SPCG-2).
AB  - The skeleton is the most frequent site of metastases from prostate cancer.
      Quantitation of the amount of tumor burden has a great prognostic value and is of
      importance for clinical trials. The present study reviews 194 bone scans from the
      SPCG-2 study which consisted of 294 patients entered into a randomized
      prospective multicenter trial, comparing total androgen suppression with standard
      treatment in patients with metastatic prostatic cancer (orchiectomy plus
      cyproterone acetate vs. orchiectomy plus placebo). Evaluation of the initial bone
      scans based on the extension of the disease (EOD) as proposed by Soloway and
      associates gives a convenient stratification of the patients. With regard to time
      to progression and cancer-related as well as overall survival, this EOD grading
      system had a significant prognostic value (p < 0.001). There was no statistical
      difference between the two treatment arms in the different categories of the EOD
      grading system with regard to time to progression and time to death. By analyzing
      exclusively the subgroup of patients with minimal disease (EOD I) and good
      performance status (WHO score 0), there was a nonsignificant trend toward a
      better 2-year progression-free survival as well as a better 2-year cancer-related
      survival for those who were subjected to total androgen suppression as compared
      with the patients subjected to the standard treatment (orchiectomy).

PMID- 8521895
TI  - Pressure/cross-sectional area relations in the proximal urethra of healthy males.
      Part 1: Elastance and estimated pressure in the uninstrumented urethra.
AB  - The pressure/cross-sectional area relation in the resting urethra during the
      storage phase was studied in 31 healthy male volunteers aged 23-85 years.
      Measurements were performed at 5-mm intervals from the bladder neck and beyond
      the region of high pressure, and the elastance and estimated pressure in the
      uninstrumented urethra (Po) were calculated at each measurement location. All
      subjects were further evaluated by means of symptom score, prostatic volume
      determined by rectal ultrasound, urethral pressure profile, cystometry, and
      pressure flow. The elastance and Po both varied along the urethra, with
      significantly higher values of both parameters in the sphincteric region as
      compared to the prostatic area. A significant positive correlation was found
      between Po and age in the prostatic parts of the urethra, whereas no correlation
      could be demonstrated between elastance and age in any part of the urethra. These
      results indicate that the prostatic parts of the urethra are readily distensible
      at modest intraluminal pressures as compared to the sphincteric segment, and that
      the intraluminal pressure required to obtain a given distension of this segment
      of the urethra seems to increase with age. It is suggested that the technique may
      prove of value in the elucidation of pathophysiological mechanisms related to
      benign prostatic hyperplasia, and that the technique may bring new insight into
      the mode of action of various treatment modalities for this disease.

PMID- 8521896
TI  - Pressure/cross-sectional area relations in the proximal urethra of healthy males.
      Part 2: Power generation during voluntary contraction.
AB  - The power generation in the proximal urethra during voluntary squeezing was
      studied in 30 healthy male volunteers aged 23-85 years. Measurements were
      performed at 5-mm intervals from the bladder neck and beyond the region of high
      pressure, and the maximum power generation during contraction was calculated at
      each measurement location. All subjects were further evaluated by means of
      symptom score, prostatic volume determined by rectal ultrasound, urethral
      pressure profile, cystometry, and pressure flow. There was a significant
      variation in power generation along the urethra, with minimum values in the
      prostatic segments and an approximately 5-fold increase in the high pressure
      zone. Power generation remained high in the urethral segment distal to the high
      pressure zone. No correlation between age and power generation could be
      demonstrated in any part of the urethra. The technique employed does not allow
      for a differentiation of the individual muscles involved, however, it is
      suggested that the pelvic floor dominates above the level of the perineal
      membrane, whereas the striated muscles of the penis may influence the proximal
      part of the spongious urethra. Physiologically, the contractile capability of the
      male urethra is probably important for the continence function, as well as it may
      be of significance for the normal ejaculatory function.

PMID- 8521897
TI  - Color Doppler ultrasonographic scanning in prostatitis: clinical correlation.
AB  - Color Doppler and endorectal ultrasonography were performed in 25 patients with
      acute prostatic syndromes (APS; 13 acute and 12 chronic recurrent forms). In
      addition, 7 patients with asymptomatic chronic prostatitis, 13 men with prostatic
      carcinoma and 6 healthy young volunteers were studied. In the 25 APS, a marked
      increase in color was observed in the cervicourethral site and/or around the
      ejaculatory ducts and close to the seminal vesicles. The observed pattern is
      probably explained by vessel dilatation due to acute inflammation. The color
      increase in these 25 patients was greater than in the 6 normal prostates and 8/9
      prostate carcinomas. Moreover, we observed that color intensity matched the
      severity of symptoms in APS.

PMID- 8521898
TI  - Effects of intravenous thyrotropin-releasing hormone on urethral closure pressure
      in females with voiding dysfunction.
AB  - OBJECTIVE: The aim of this work was to investigate the effects of intravenously
      administered thyrotropin-releasing hormone (TRH) on the urethral closure pressure
      in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Sixteen female
      subjects with either bladder outlet obstruction (BOO) or detrusor underactivity
      were included in the study. Following randomization, 8 subjects (3 BOO, 5
      detrusor underactivity) received 200 micrograms of TRH intravenously, and 8 (4
      BOO, 4 detrusor underactivity) received saline (placebo). Standard fluid fill
      urethral pressure profilometry was performed at baseline and 2, 3, 5, 10, 15, and
      20 min following TRH injection, measuring functional profile length (FPL),
      maximum urethral closure pressure (UCP), and closure pressures at the proximal
      quarter of the FPL (1/4 UCP) and at the distal quarter of the FPL (3/4 UCP).
      RESULTS: Significant reductions were found in both FPL (p = 0.022) and 3/4 UCP (p
      = 0.014) in the 'active' group as compared with the 'placebo' group. CONCLUSIONS:
      TRH administration significantly reduces the distal urethral closure pressure.
      Clarification of the mechanism of action of TRH on the urethra may point the way
      towards new developments in the management of female voiding dysfunction.

PMID- 8521899
TI  - Adhesion of calcium oxalate crystals to Madin-Darby canine kidney cells and some
      effects of glycosaminoglycans or cell injuries.
AB  - The present investigation studied the quantitative adhesion of calcium oxalate
      monohydrate (COM) crystals to the surface of Madin-Darby canine kidney cells,
      which exhibit many characteristics of renal cortical collecting tubule cells. COM
      crystals adhered to the cell surface, and the attachment showed a time and
      concentration dependency with plateau. The results suggested that the attachment
      of microcrystals to the cortical tubular cell might be one of the earliest
      processes in the formation of kidney stones. Pretreatment with glycosaminoglycans
      significantly reduced the adherent crystals. Injuries to the Madin-Darby cells
      induced by 0.1 M HCl and gentamicin resulted in significant decreases of COM
      crystal adhesion to the cell surface. It was suggested that urinary
      glycosaminoglycans might play some critical role in preventing crystal adhesion
      to these cellular membranes and that cell injuries might not be essential for the
      attachment of microcrystals to the tubular cells.

PMID- 8521900
TI  - CO2 laser for therapeutic circumcision in adults.
AB  - The use of carbon dioxide laser for 38 posthetomies or therapeutic circumcisions
      in the treatment of phimosis, paraphimosis, balanitis of Zoon or a genital
      infection by the human papillomaviurs permits clean and hemostatic incisions. The
      clean and dry wound produced by the carbon dioxide beam offers several
      advantages. It reduces the surgeon's risk of contamination by the HIV virus and
      the subsequent sear is regular and without edema. In 57% of primary phimosis
      cases, the histological analysis showed a lichen sclerosus et atrophicus.

PMID- 8521901
TI  - Renal cell carcinoma in acquired renal cystic disease 3 years after successful
      kidney transplantation. Two case reports and review of the literature.
AB  - Acquired renal cystic disease (ARCD) has a prevalence of up to 90% in patients
      with endstage renal failure and an uncommonly high potential of developing into
      renal cell carcinoma. After renal transplantation, regression of an established
      ARCD is possible, suggesting a protective effect of transplantation against
      tumors in the native kidneys. Two case reports describing hypernephromas in
      kidneys with ARCD 3 years after successful renal transplantation are presented.
      One patient died 6 weeks after nephrectomy due to metastatic disease, although
      there were no metastases at the time of operation. The other patient lives with
      no evidence of disease since 10 months. This report confirms the need of annual
      sonography of the native kidneys also in renal transplant patients with
      consecutive computed tomography scanning of suspicious lesions.

PMID- 8521902
TI  - Primary osteosarcoma of the kidney. Case report and review of literature.
AB  - Primary osteosarcoma of the kidney is an extremely rare phenomenon with less than
      20 previously reported cases in the English literature since 1936. Diagnosis
      usually is made in advanced stages of disease with weight loss, palpable tumor,
      flank pain and gross hematuria being the characteristic features of clinical
      presentation. Radiographically bizarre renal calcifications may be suggestive of
      this uncommon neoplasm. The atypic location is explained by metaplastic changes
      of originally primitive embryonic mesenchymal tissue. Though the primary
      treatment for sarcomas is surgical resection, because of their usual late and
      high stage presentation multimodal adjuvant therapy may be desirable. We describe
      the clinical course of a 48-year-old male patient with a primary renal
      osteosarcoma discovered by ultrasound. A marked reduction of vital tumor cells
      and an impressive increase of neoplastic bone formation following
      polychemotherapy is demonstrated histopathologically. The principal clinical
      findings, differential diagnosis, etiology, pathogenesis and treatment modalities
      of this uncommon malignancy are discussed.

PMID- 8521903
TI  - Effects of putative cognition enhancers on the NMDA receptor by [3H]MK801
      binding.
AB  - Piracetam, aniracetam, and D-cycloserine were tested for their ability to reduce
      inhibition of [3H]MK801 (dizocilpine) binding by 100 microM kynurenate. Piracetam
      (100 microM-1 mM) failed to reduce inhibition by kynurenate but stimulated
      [3H]MK801 binding in the absence of kynurenate. In contrast, D-cycloserine (30
      microM-1 mM) and aniracetam markedly reduced this inhibition by kynurenate. Thus,
      cognition enhancers might function via at least some subtypes of NMDA receptors.

PMID- 8521904
TI  - Modification of behavioral effects of 8-hydroxy-2-(di-n-propylamino)tetralin
      following chronic ethanol consumption in the rat: evidence for the involvement of
      5-HT1A receptors in ethanol dependence.
AB  - Behavioral effects induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT;
      i.e., lower lip retraction, flat body posture, and forepaw treading) were
      examined in rats during ethanol withdrawal following a 2-week period of access to
      a liquid diet containing 9% (v/v) ethanol. After an 18 h withdrawal period,
      tolerance to 8-OH-DPAT-induced flat body posture and, conversely, sensitization
      to the effects of 8-OH-DPAT on lower lip retraction were observed in the 9%
      ethanol group as compared to control rats fed an isocaloric diet. In contrast, 8
      OH-DPAT-induced forepaw treading in the 9% ethanol group was not significantly
      different in comparison to control rats. Plasma corticosterone levels were
      significantly higher in the ethanol-exposed group than in control animals, an
      effect which was not additive with the increase in corticosterone levels normally
      observed after the administration of low doses of 8-OH-DPAT. Altered flat body
      posture and lower lip retraction responses to a submaximal dose of 8-OH-DPAT (2.5
      mg/kg i.p.) were still observed as late as 3 days after withdrawal of the 9%
      ethanol liquid diet, but were no longer apparent at 7 days. Interestingly,
      prominent ethanol withdrawal signs such as tremor and rigidity, while occurring
      on the first day, were completely absent on the third day. Taken together, these
      results indicate that chronic ethanol exposure differentially alters sensitivity
      to several pharmacological effects of the 5-HT1A receptor ligand 8-OH-DPAT. They
      further support the involvement of 5-HT (5-hydroxytryptamine, serotonin) systems
      in alcohol abuse and therapeutic interventions using 5-HT1A ligands.

PMID- 8521905
TI  - Chronic alcoholization alters the expression of 5-HT1A and 5-HT1B receptor
      subtypes in rat brain.
AB  - The expression of central 5-HT1A and 5-HT1B receptors was studied in several
      brain areas of rats subjected to a 2-week period of chronic alcoholization,
      followed by 18 h withdrawal. Quantitative autoradiography indicated that the
      ethanol treatment provoked an increase (approximately +30%) in the labeling by
      [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and [3H]N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide
      ([3H]WAY-100635) of 5-HT1A autoreceptors in the dorsal raphe nucleus, accompanied
      by a concomitant decrease in the labeling of postsynaptic 5-HT1A receptors in the
      hippocampus (approximately -20%), anterior (approximately -30%) and posterior
      (approximately -32%) cortices. These changes were associated with a tendency
      toward an increase and decrease in 5-HT1A mRNA levels in the anterior raphe area
      and hippocampus, respectively, suggesting that the changes observed are due to
      modifications in 5-HT1A receptor protein synthesis. The autoradiographic labeling
      of 5-HT1B receptors by serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide
      ([125I]GTI) was found to increase (+55%) in the globus pallidus of alcoholized
      rats. Interestingly, a significant increase (+57%) in 5-HT1B receptor mRNA levels
      was observed in the striatum, which contains cell bodies of neurons projecting
      into the globus pallidus. These data suggest that altered sensitivity of
      chronically alcoholized rats to 5-HT1A and 5-HT1B receptor ligands may result
      from alcohol-induced changes in the transcription of the genes encoding these
      receptors.

PMID- 8521906
TI  - Effects of antipsychotics on cognitive behaviour in rats using the delayed non
      match to position paradigm.
AB  - The acute effects of the dopamine D1 receptor antagonist SCH 23390 [(R)-(+)-8
      chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepi n-7-ol d hemimaleat,
      the dopamine D2 receptor antagonists raclopride and haloperidol, the compounds
      with mixed receptor profiles clozapine, risperidone and sertindole, the alpha 1
      adrenoceptor antagonist prazosin and scopolamine were investigated in a delay
      response task, a test for working memory, for rats. SCH 23390 induced a delay
      dependent impairment of the performance. Raclopride, haloperidol, clozapine, and
      risperidone induced a delay-independent impairment. Sertindole was without
      effect. The specific (delay-dependent) and unspecific (delay-independent) effects
      on working memory of the dopamine D1 and D2 receptor antagonists, respectively,
      were associated with the dominance of dopamine D1 receptors in the prefrontal
      cortex and of dopamine D2 receptors in the basal structures of the brain.
      Prazosin did not affect working memory; however, a reduction in intertrial
      responses was found. Scopolamine induced a delay-independent impairment. It is
      concluded that the compounds have different activity profiles in this cognitive
      task. This finding may have important implications for the development of
      antipsychotics with a lower propensity for cognitive side effects.

PMID- 8521907
TI  - Hyporesponsiveness to nitrovasodilators in rat aorta incubated with endotoxin and
      L-arginine.
AB  - We studied the effect of L-arginine on relaxation responses to sodium
      nitroprusside or SIN-1 (3-morpholinosydonimine-N-ethyl-carbamine) in the rat
      thoracic aorta incubated with endotoxin. Sodium nitroprusside or SIN-1 produced a
      reproducible relaxation in the aorta incubated for 12 h with endotoxin. However,
      the response to both nitrovasodilators was remarkably attenuated when the aorta
      was preincubated for 12 h with endotoxin and L-arginine. D-Arginine could not
      substitute for L-arginine. The attenuated response to sodium nitroprusside or SIN
      1 was partially restored by the inhibition of nitric oxide (NO) production with N
      omega-nitro-L-arginine. Cycloheximide prevented the inhibitory effect of
      preincubation with L-arginine. These results suggest that the prolonged exposure
      to muscle-derived NO induces hyporesponsiveness to nitrovasodilators.

PMID- 8521908
TI  - Effect of antidepressants on striatal and accumbens extracellular dopamine
      levels.
AB  - The effect of the selective serotonin (5-hydroxytryptamine, 5-HT) reuptake
      inhibitor, fluoxetine (10 mg/kg s.c.), two tricyclic antidepressants,
      clomipramine (10 mg/kg s.c.) and imipramine (10 mg/kg s.c.), and vehicle on
      extracellular dopamine levels was studied in rat nucleus accumbens and striatum
      by in vivo microdialysis. Fluoxetine produced significant decreases in
      extracellular dopamine levels in both the nucleus accumbens and striatum (mean
      maximum percentage decrease: 58% and 57% of pre-drug baseline, respectively). In
      contrast, imipramine and clomipramine significantly increased extracellular
      dopamine in the striatum (148% and 150%, respectively) compared to the effect of
      vehicle alone (118%). These results suggest that the selective serotonin reuptake
      inhibitor, fluoxetine, and the tricyclic antidepressants, clomipramine and
      imipramine, affect dopaminergic activity in diverse ways and in a region-specific
      manner. Thus, the antidepressant effect of these drugs is unlikely to be related
      to their acute effects on dopaminergic neurotransmission. The differential
      effects of the selective serotonin reuptake inhibitor and tricyclic
      antidepressants on extracellular dopamine could account for other differences in
      their clinical and side effect profiles. Further studies of the chronic effects
      of the selective serotonin reuptake inhibitor and the tricyclic antidepressants
      on dopaminergic activity are required to elucidate the role of dopamine in the
      antidepressant effect.

PMID- 8521909
TI  - Peripheral injection of arginine8-vasopressin increases Fos in specific brain
      areas.
AB  - Learned behaviors and tolerance to ethanol can be maintained by peripheral
      injection of arginine8-vasopressin (vasopressin) under conditions in which they
      would otherwise be lost. However, the sites of this action in the brain have not
      been clearly identified. Using a polyclonal antibody raised against Fos and Fos
      like proteins, we have demonstrated increases in immunoreactive Fos and Fos-like
      proteins in the suprachiasmatic, supraoptic and paraventricular nuclei of the
      hypothalamus, and lesser increases in piriform cortex and amygdala, of the rat 2
      h after a s.c. injection of vasopressin. Our results suggest that the exogenous
      vasopressin may exert its central action by activating a cellular immediate early
      gene in specific brain regions.

PMID- 8521910
TI  - Muscarinic receptors modulate the afterhyperpolarizing potential in neostriatal
      neurons.
AB  - The actions of carbachol were studied on the firing response of neostriatal
      neurons recorded intracellularly from in vitro slice preparations of the rat
      brain. Carbachol (1-10 microM) reversibly reduced the afterhyperpolarization in
      neostriatal neurons. This effect was accompanied by an increase in both firing
      frequency and input resistance in the subthreshold voltage range. Atropine (1-10
      microM) reversibly blocked carbachol effects, suggesting muscarinic receptor
      modulation. Pirenzepine (up to 1 microM), but not AF-DX 384 (10 microM) or
      gallamine (30 microM), blocked the effects of carbachol on the
      afterhyperpolarization. The protein kinase C activator, phorbol 12,13 dibutyrate,
      but not the inactive phorbol ester, 4 alpha-phorbol 12-myristate 13-acetate,
      mimicked carbachol effects. The results suggest that muscarinic receptors,
      probably of the M1 type, regulate neostriatal excitability by modulating
      afterhyperpolarization.

PMID- 8521911
TI  - Multiple mechanisms of bradykinin-induced contraction in rat and guinea pig
      smooth muscles in vitro.
AB  - Bradykinin caused graded contraction in the guinea pig ileum, trachea and urinary
      bladder and rat uterus and vas deferens in vitro. The order of potency (EC50, nM)
      was: ileum (3) > uterus (5) > trachea (15) > vas deferens (41) > urinary bladder
      (52) and the maximal responses (percentage to 80 mM KCl) were: 152 +/- 8 (ileum),
      122 +/- 6 (uterus), 97 +/- 3 (urinary bladder), 75 +/- 5 (trachea) and 33 +/- 3
      (vas deferens). Responses to bradykinin in guinea pig ileum and urinary bladder
      and rat vas deferens and uterus were markedly attenuated in Ca(2+)-free medium
      with or without EGTA or by nicardipine, whereas those in guinea pig trachea
      depended almost exclusively on intracellular Ca2+ sources which were sensitive to
      ryanodine. Treatment of the animals with pertussis toxin only inhibited
      bradykinin-induced contraction of the rat uterus. Furthermore, the protein kinase
      C inhibitors, H7 (5-isoquinolinysulfonyl-2-methyl-piperazine) and staurosporine,
      antagonized in a graded manner bradykinin responses in guinea pig ileum and
      trachea and rat vas deferens, indicating the possible dependence on activation of
      protein kinase C mechanisms, while responses of the rat uterus rely on coupling
      by a pertussis toxin-sensitive G protein. Thus, bradykinin acting at B2 receptors
      may induce contractions in several smooth muscles from rat and guinea pig through
      activation of multiple second messenger pathways.

PMID- 8521912
TI  - Differential effects of repeated administration of novel antipsychotic drugs on
      the activity of midbrain dopamine neurons in the rat.
AB  - Five potential antipsychotics (i.e. risperidone, olanzapine, seroquel,
      ziprasidone and amperozide) were given daily for 21 days to rats and the effect
      on the number of spontaneously active dopamine neurons in ventral tegmental area
      and substantia nigra pars compacta was determined. Standard electrophysiological
      measurements (i.e. single unit recording technique) were used. Risperidone,
      olanzapine and amperozide showed some selectivity (at one particular dose) for
      decreasing the number of active dopamine neurons in the ventral tegmental area.
      However, risperidone induced a U-shaped dose-response curve. The highest dose of
      amperozide inhibited the activity in substantia nigra pars compacta, showing a
      liability to induce extrapyramidal side-effects. Seroquel and ziprasidone
      inhibited the activity in both areas indicating a classical antipsychotic profile
      (i.e. high liability to cause extrapyramidal side-effects).

PMID- 8521913
TI  - Release of somatostatin-like immunoreactivity from enriched enteric nerve
      varicosities of rat ileum.
AB  - Synaptosomes were isolated from rat ileum by various steps of differential
      centrifugation. The peptide content for somatostatin-like immunoreactivity was
      used as marker for neuronal membranes. The enriched synaptosomal fraction (P2)
      showed a good enrichment of somatostatin content (4-fold) in comparison to the
      post-nuclear supernatant. The basal release of somatostatin-like immunoreactivity
      was 26 +/- 3 pg/mg tissue protein. KCl-evoked depolarization (65 mM) caused a
      significant increase of somatostatin-like immunoreactivity release (72 +/- 11
      pg/mg, n = 12, P < 0.001) compared to basal release. In Ca(2+)-free medium the
      evoked release of somatostatin-like immunoreactivity was abolished. A substantial
      increase of somatostatin-like immunoreactivity release (52 +/- 7 pg/mg, n = 12, P
      < 0.05) was also observed in the presence of the Ca2+ ionophore A-23187. The
      cholinergic agonist carbachol elicited a dose-dependent release of somatostatin
      like immunoreactivity (10(-7) M: 54 +/- 8 pg/mg, 10(-6) M: 63 +/- 6 pg/mg, 10(-5)
      M: 53 +/- 5 pg/mg, n = 12, P < 0.001), which was blocked by atropine (10(-6) M:
      35 +/- 6 pg/mg, n = 12, P < 0.001), but not by hexamethonium. Other presynaptic
      modulating substances such as serotonin, the selective neurokinin-B agonist [beta
      Asp4,MePhe7]neurokinin B-(4-10), neurotensin, cholecystokinin-8, caerulein and
      pentagastrin had no stimulatory effect on release of somatostatin-like
      immunoreactivity. In summary, somatostatin-like immunoreactivity can be released
      from enteric synaptosomes by both depolarization with KCl and cholinergic
      stimulation via a muscarinic mechanism. The synaptosomes of intrinsic nerves
      offer an approach to study release of neuronal somatostatin on the subcellular
      level.

PMID- 8521915
TI  - Complex role of peripheral adenosine in the genesis of the response to
      subcutaneous formalin in the rat.
AB  - When applied peripherally, adenosine has been shown to be pronociceptive in a
      number of animal and human models. Recent evidence has implicated adenosine as a
      significant mediator in the inflammatory process. In this study using rats, we
      have examined the effect of adenosine and of selective adenosine A1 and A2
      receptor agonists and antagonists on the response to a subcutaneous injection of
      formalin into the rat hindpaw. Adenosine co-injected with formalin 0.5%
      significantly increased flinching in both phases in a dose-dependent manner. The
      highest dose of adenosine had no behavioral effect on its own. The adenosine A2
      receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido
      adenosine hydrochloride (CGS-21680), at a dose of 1.5 nmol, increased flinching
      associated with 0.5% formalin injection but at higher doses produced depressant
      effects due to systemic absorption. The adenosine A1 receptor agonist N6
      cyclohexyladenosine produced only systemic behavioral effects as determined by
      contralateral application. The flinching response to 2.5% formalin was
      significantly decreased by the adenosine A2 receptor antagonist 3,7-dimethyl-1
      propargylxanthine (DMPX). In contrast, 8-cyclopentyl-1,3-dimethylxanthine (CPT),
      the selective adenosine A1 receptor antagonist augmented the response to 2.5%
      formalin. The non-selective adenosine receptor antagonist caffeine had no
      significant effect over a wide range of doses. In summary, exogenous adenosine
      enhances nociception in the formalin test, probably via a peripheral A2 receptor
      mediated action. Endogenous adenosine, acting at both A1 and A2 receptors,
      appears to be involved in the formalin-induced inflammatory response.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8521914
TI  - Nerve function in galactosaemic rats: effects of evening primrose oil and
      doxazosin.
AB  - Rats were fed for 6 weeks with a 40% galactose diet to chronically stimulate the
      polyol pathway. Sciatic motor and saphenous sensory nerve conduction velocity
      deficits of 22% and 14% respectively developed. Treatment with evening primrose
      oil or doxazosin from galactosaemia induction partially (approximately 60%)
      prevented the development of reduced motor and sensory conduction, the former
      treatment being more successful than the latter. Sciatic nerve resistance to
      hypoxic conduction failure was 49% increased by galactosaemia. This abnormality
      was 27% and 43% prevented by doxazosin and evening primrose oil respectively.
      Galactosaemic sciatic nerves had a 10% increase in water content and endoneurial
      capillary density was 24% reduced. While neither treatment affected water
      content, both caused angiogenesis, elevating capillary density by approximately
      16%. The data support the hypothesis that, as in experimental diabetes mellitus,
      the main effect of polyol pathway activation on peripheral nerve function occurs
      indirectly via a neurovascular action.

PMID- 8521916
TI  - The non-competitive AMPA/kainate receptor antagonist, GYKI 52466, potentiates the
      anticonvulsant activity of conventional antiepileptics.
AB  - 1-(4-Aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride
      (GYKI 52466), up to 5 mg/kg, did not influence the electroconvulsive threshold
      but potentiated the anticonvulsant activity of valproate, carbamazepine and
      diphenylhydantoin against maximal electroshock-induced convulsions in mice. No
      potentiation was observed in the case of phenobarbital. Moreover, this non-NMDA
      receptor antagonist did not influence the plasma levels of the antiepileptic
      drugs studied, so a pharmacokinetic interaction, in terms of total and free
      plasma levels, is not probable. The combined treatment of GYKI 52466 with either
      carbamazepine or diphenylhydantoin (providing a 50% protection against maximal
      electroshock) was devoid of significant side effects (motor and long-term memory
      impairment). Valproate applied at a dose equal to its ED50 caused serious
      worsening of motor coordination and long-term memory. It is noteworthy that the
      combined treatment of GYKI 52466 with valproate was superior to valproate alone,
      as regards adverse effects. The results suggest that concomitant administration
      of GYKI 52466 with some conventional antiepileptic drugs may offer a novel
      approach in the treatment of epilepsy.

PMID- 8521917
TI  - Influence of combined treatment with NMDA and non-NMDA receptor antagonists on
      electroconvulsions in mice.
AB  - alpha-Amino-3-hydroxy-5-methyl-isoxazole-4-propionate/kainate (AMPA/kainate)
      receptor antagonists (at subthreshold doses against electroconvulsions), 1-(4
      aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466 at
      maximally 5 mg/kg) and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX
      at maximally 20 mg/kg) enhanced the protective effects of NMDA receptor
      antagonists, MK-801 (dizocilpine) or 2-(2-carboxypiperazine-4-yl)-1-propenyl-1
      phosphonic acid (D-CPP-ene), against electroconvulsions. Similarly, MK-801 or D
      CPP-ene reduced the ED50 values of both NBQX and GYKI 52466 against maximal
      electroshock. The adverse effects of D-CPP-ene, evaluated in the chimney and
      rotorod tests, were potentiated by both GYKI 52466 (2.5 mg/kg) and NBQX (10
      mg/kg). Also, D-CPP-ene (0.1 mg/kg) worsened the motor performance of mice
      pretreated with GYKI 52466 in the rotorod test. Neither MK-801 (0.025 mg/kg) nor
      D-CPP-ene (0.1 mg/kg) affected the NBQX-induced impairment of motor coordination.
      Similarly, GYKI 52466 (2.5 mg/kg) or NBQX (10 mg/kg) did not influence the
      performance of mice treated with MK-801 (0.2 mg/kg). It may be concluded that the
      blockade of more than one subtype of glutamate receptors leads to a more
      pronounced anticonvulsive effect when compared with the effect of blockade of an
      individual receptor subtype. In some cases more efficient seizure protection was
      not associated with increased adverse effects.

PMID- 8521918
TI  - Methylcobalamin attenuates the hypoxia/hypoglycemia- or glutamate-induced
      reduction in hippocampal fiber spikes in vitro.
AB  - The effects of methylcobalamin, a vitamin B12 analogue, on the
      hypoxia/hypoglycemia- or glutamate-induced reduction in hippocampal CA1
      presynaptic fiber spikes elicited by Schaffer collateral stimulation in rat brain
      slices were evaluated. Hippocampal slices were exposed to 15 min of
      hypoxia/hypoglycemia, and then these slices were returned to oxygenated and
      glucose-containing buffer for 3 h. Hypoxia/hypoglycemia reduced CA1 presynaptic
      potentials in vitro. Treatment with 10 microM methylcobalamin attenuated the
      impairment of CA1 presynaptic potentials induced by hypoxia/hypoglycemia or
      glutamate application (10 mM). Daily injection of methylcobalamin (0.5 mg/kg
      i.p./day) for 3 days in vivo also attenuated the hypoxia/hypoglycemia- or
      glutamate-induced reduction in presynaptic potentials in hippocampal slices.
      Pretreatment with cyanocobalamin at 10 microM failed to attenuate the impairment
      of CA1 presynaptic potentials. However, daily injection of cyanocobalamin (0.5
      mg/kg i.p./day) for 3 days caused a protective action against the
      hypoxia/hypoglycemia- or glutamate-induced functional deficit. Furthermore, co
      treatment of L-arginine (100 microM), a substrate for nitric oxide synthase, with
      methylcobalamin in vitro reversed the methylcobalamin-induced functional
      recovery. The present results demonstrate that methylcobalamin application in
      vivo or in vitro leads to functional recovery from hypoxia/hypoglycemia- or
      glutamate-induced impairment of CA1 presynaptic potentials. Neuroprotection was
      obtained by in vivo application of cyanocobalamin, but not by its in vitro
      application. It is reported that in vivo injected cyanocobalamin converted to
      methylcobalamin in the hepatic cells. Therefore, the results suggest that a
      transmethylation reaction in the hippocampal regions may be involved in the
      methylcobalamin-induced functional recovery from ischemic impairment.

PMID- 8521919
TI  - Differential characteristics and localisation of [3H]oxazoline and
      [3H]imidazoline binding sites in rat kidney.
AB  - Comparative autoradiography revealed that the imidazolines [3H]p-aminoclonidine
      and [3H]idazoxan labelled high densities of alpha 2A-adrenoceptor sites in the
      inner medulla and inner stripe of the outer medulla of rat kidney. In contrast,
      the oxazoline [3H]rilmenidine labelled a high density of non-adrenergic sites in
      the cortex and outer stripe of the outer medulla, a lower density in the inner
      stripe and inner medulla and a low density of alpha 2A-adrenoceptor sites in
      inner medulla. The existence of novel, non-adrenergic oxazoline sites of
      potential functional importance in rat kidney has important implications for the
      classification of imidazoline receptors.

PMID- 8521920
TI  - The propellant unilateral magnetic appliance (PUMA): a new technique for
      hemifacial microsomia.
AB  - A new appliance with samarium cobalt magnets embedded in unilateral blocks of
      acrylic is described, as a way of stimulating an autogenous costochondral graft,
      in a case with hemifacial microsomia. Laser scan images are used to illustrate a
      reversion towards facial soft tissue symmetry, over a 3-year period of treatment.

PMID- 8521921
TI  - Functional masticatory evaluation in hemifacial microsomia.
AB  - The features of hemifacial microsomia with unilateral condylar hypoplasia in a 9
      year-old female patient were analysed in a multidisciplinary fashion.
      Cephalometric roentgenograms revealed malformation of the mandible, with the
      right condylar process being smaller than the left. In addition, the right
      maxillary alveolar process was underdeveloped. Closed view radiography with
      oblique lateral transcranial projection (by modified Schuller's method) of the
      temporomandibular joint revealed an anterior dislocation of the condyle on the
      unaffected side. Computed tomography (CT) of the masticatory muscles demonstrated
      that the medial pterygoid muscle on the affected side, unlike the other muscles,
      was larger than that on the unaffected side. The surface electromyographic
      activities of the temporal and masseter muscles and reduction of the maximum bite
      force on the affected side during clenching corresponded with the CT findings.
      The hypertrophy of the medial pterygoid muscle on the affected side was
      considered likely to be a compensatory adjustment to keep the mandible centred. A
      three-dimensional study of the movement of the mandible revealed that the condyle
      on the affected side moved vertically and that the rotational centre was located
      antero-inferior to the condylar process during maximum jaw opening and closing
      movements. These findings suggested lack of articular guidance. Moreover, the
      unaffected condylar process showed considerable backward movement during
      retrusion and ipsilateral excursion of the mandible. The mandibular head on the
      unaffected side showed obvious protraction during all jaw movements, which might
      have induced the overgrowth of the condylar head on the unaffected side in this
      growing child.

PMID- 8521922
TI  - Discriminant analysis in treatment evaluation of ectopic eruption of the
      maxillary first permanent molars.
AB  - The value of an analytical routine which could be used in the evaluation of
      clinical studies was assessed. Stepwise discriminant analysis with stepwise
      selection/elimination was used to reduce the amount of data without losing
      information before further analyses with canonical discriminant analysis. The
      purpose of canonical discriminant analysis was to reveal interactions between
      factors associated with the ectopic eruption of the first permanent molars. Two
      canonical discriminant functions were used to determine the accuracy of diagnosis
      and the effect of treatment. This information consisted of variables which were
      the most important (their ranks) and their single correlations (structure
      coefficients) to the function itself. This information was interpreted
      clinically. The coefficients of the canonical discriminant functions can be used
      for classification purposes. The use of a scatterplot instead of simple
      classification tables is suggested. The scatterplot was particularly informative
      on how well the procedure discriminated between groups. A table based on original
      data is included to allow the reader to test the validity of the findings on
      cases of his/her own. This multivariate strategy avoids spurious
      intercorrelations between two or more variables analysed as multiple single
      factors that has a high risk of erroneous conclusions.

PMID- 8521923
TI  - Long-term treatment effects in children with ectopic eruption of the maxillary
      first permanent molars.
AB  - Forty-five out of forty-six children with irreversible ectopic eruption of at
      least one of the maxillary first permanent molars and treated with cervical
      headgear could be reached for a 10-year follow-up. The mean age at the start of
      treatment was 8.3 years (range 6.5-9.9 years). Forty-six individuals served as
      controls. Two forms of discriminant analysis were used to evaluate treatment
      effects. The main results are illustrated by pretreatment and 10-year follow-up
      scatter plots. The latter showed the patients and controls were intermingled,
      indicating a uniformity of the cases after treatment. All negative side-effects
      of the treatment were eliminated at the follow-up. Cervical traction treatment is
      a good choice for correcting ectopically erupted upper first molars in suitable
      cases.

PMID- 8521924
TI  - Prevalence of temporomandibular joint dysfunction (TMJD) in Chinese children and
      adolescents. A cross-sectional epidemiological study.
AB  - The aim of this study was to investigate the prevalence of temporomandibular
      joint dysfunction (TMJD) in Chinese children and adolescents, and the
      relationship between TMJD and type of occlusion. The sample consisted of 3105
      Chinese children, 3-19 years of age, divided into four groups by the stage of
      dental maturation. The prevalence of TMJD for the entir group was 17.9 per cent
      and there was no significant sex difference. TMJD increased in the mixed and
      early permanent dentitions, but decreased in the permanent and deciduous
      dentitions. In the subjects with TMJD, the most common sign was sound (87.7 per
      cent), followed by abnormal jaw movement (23.6 per cent), but pain was registered
      in 0.6 per cent only. A single sign was registered in 88.5 per cent, a
      combination of sound and abnormal jaw movement in 11.0 per cent, and combinations
      of other signs in less than 1.0 per cent. Sound as a single sign increased with
      the specific stages of dental development (P < 0.001).

PMID- 8521925
TI  - Expression of neuropeptides (CGRP, substance P) during and after orthodontic
      tooth movement in the rat.
AB  - The present study was designed to investigate the changes in patterns of
      calcitonin gene-related peptide (CGRP) and substance P (SP) innervation during
      buccally-directed orthodontic tooth movement (OTM) of the first maxillary molar
      in the rat. In addition, the CGRP- and SP-innervation was examined 14 and 28 days
      after the orthodontic force was discontinued. Comparisons were made with the
      innervation found in control animals. Orthodontic appliances produced a buccally
      directed force in the range of 20-50 g on the upper right first molar for either
      24 hours or 3 days. When the orthodontic appliances were removed one group of
      animals were killed immediately, whereas the other groups were killed after a
      healing period of 14 days or 28 days. After fixation the upper jaws were
      decalcified, frozen, and sectioned in the frontal plane at the level of the first
      and second molars. The sections were processed for CGRP, SP, and routine
      morphology. An increase was found in the number of nerve fibres showing CGRP-like
      immunoreactivity (LI) in the pulp, periodontal ligament (PDL) and marginal
      gingivae with the fibres showing a higher intensity of immunolabelling after 24
      hours or 3 days of OTM. The contralateral first upper molar showed an increase in
      the expression of CGRP. Fourteen days after removal of the appliances, there was
      still a marked CGRP-innervation of the PDL in test teeth as well as in
      contralateral teeth. After 28 days, a decrease in CGRP-innervation was observed,
      but this innervation was still more pronounced than that found in the controls.
      The pattern of SP-innervation changed similarly to that of the CGRP-innervation,
      however, the nerve fibres showing SP-LI were considerably fewer than those
      showing CGRP-LI at all stages and in all areas. This study suggests that CGRP-
      and SP-changes not only occur in the tooth exposed to buccally directed OTM, but
      also in the contralateral tooth and that the changes are evident for a
      considerable time after terminating OTM.

PMID- 8521926
TI  - Psychiatric epidemiology.

PMID- 8521927
TI  - Schizophrenia: recent epidemiologic issues.

PMID- 8521928
TI  - Perinatal risk factors and schizophrenia: selective review and methodological
      concerns.

PMID- 8521929
TI  - Review of psychiatric epidemiologic research on disasters.

PMID- 8521930
TI  - Work conditions as explanations for the relation between socioeconomic status,
      gender, and psychological disorders.

PMID- 8521931
TI  - Psychiatric illness and cardiovascular disease risk.
AB  - Studies evaluating the risk of cardiovascular disease in the psychiatrically ill
      yield mixed results. Phobic anxiety in men is associated with an increased risk
      for cardiovascular disease, particularly sudden coronary death. This finding is
      in need of replication in women, and hypotheses regarding the potential
      mechanisms for this association warrant pilot testing. Other than this finding,
      there is only weak evidence supporting an association between psychiatric illness
      and risk for cardiovascular disease. This is surprising in light of the strong
      evidence that psychiatric illness in general is associated with elevated rates of
      cigarette smoking. In addition, there may also be higher rates of hypertension,
      hypercholesterolemia, and physical inactivity in some psychiatric disorders. Why
      the high rates of cigarette smoking and possibly other cardiovascular disease
      risk factors have not translated into consistently detectable elevated
      cardiovascular disease risk in individuals with psychiatric diagnoses is not
      apparent. Weaknesses in study designs and variations in assessment methods may
      partially explain the inconsistent results. Future studies of cardiovascular
      disease in the psychiatrically ill should be prospective, use nonclinical samples
      of men and women, have clear diagnostic criteria, determine order of onset of the
      two disorders if they coexist, and control for variability in known
      cardiovascular disease risk factors.

PMID- 8521932
TI  - The epidemiology of chronic fatigue syndrome.

PMID- 8521933
TI  - Psychiatric disorders and HIV infection: impact on one another.

PMID- 8521934
TI  - Maternal depressive symptoms and the risk of poor pregnancy outcome. Review of
      the literature and preliminary findings.

PMID- 8521935
TI  - Evidence bearing on mental illness as a possible cause of violent behavior.

PMID- 8521936
TI  - Epidemiology of mental disorders in primary care settings.

PMID- 8521937
TI  - Advances in strategies for minimizing and adjusting for survey nonresponse.

PMID- 8521938
TI  - The untapped potential of case registers and record-linkage studies in
      psychiatric epidemiology.

PMID- 8521939
TI  - Recent progress in the epidemiology of major depression.

PMID- 8521940
TI  - Recent developments for diagnostic measures in psychiatry.

PMID- 8521941
TI  - Recall of psychiatric history in cross-sectional surveys: implications for
      epidemiologic research.
AB  - Data from a variety of sources suggest the possibility of significant errors in
      lifetime recall of psychiatric illness. Remote episodes of illness may often be
      forgotten, especially among patients with milder or less recurrent illness or
      those who received no treatment. These errors in recall may lead to significant
      underestimation of true lifetime prevalence and may produce the appearance of
      large temporal increases in risk in the absence of any true change. When
      assessing lifetime history, cross-sectional surveys may differentially
      underestimate prevalence in the elderly and in those with less severe or
      recurrent illness. While lifetime risk of depression and other psychiatric
      disorders may not be increasing as rapidly as suggested by cross-sectional
      surveys, the overall impact of such disorders over the life span may be
      significantly greater than previous community surveys have indicated.

PMID- 8521942
TI  - Methodological issues relevant to epidemiologic investigations of suicidal
      behaviors of adolescents.

PMID- 8521943
TI  - Looking to the future in psychiatric epidemiology.

PMID- 8521944
TI  - Progress in the epidemiology of anxiety disorders.

PMID- 8521945
TI  - Genes and recent developments in the epidemiology of Alzheimer's disease and
      related dementia.
AB  - In the search for cause or prevention of Alzheimer's disease, the traditional
      aims of analytic epidemiology have been hindered by several technical
      difficulties. The heterogeneous genetic influences on Alzheimer's disease have
      probably contributed substantially to difficulties in the detection of host or
      environmental factors associated with modified disease risk. We have discussed
      five areas of improved technical or theoretical approach, each of which has
      materially improved the prospects for future success in this endeavor. Improved
      methods of diagnosis have yielded purer samples of "cases" and have made it more
      practical to undertake population-based studies. Genetic determinants of
      Alzheimer's disease risk are being understood with increasing sophistication. A
      growing recognition of the time-dependent nature of the Alzheimer process has led
      to new and heuristically valuable ways of thinking about the disease, its causes
      (genetic and otherwise), and its prevention. While there is a growing consensus
      that Alzheimer's disease is probably not one disease but several, the limited
      success of efforts to identify distinguishable phenotypes has largely given way
      to the identification of those with various measures of disease risk and
      (probably) mechanisms on the basis of identifiable genotypic variation. Thus,
      several forms of this disease may soon be segregated for separate analysis. Two
      of the predisposing genes have apparent implications for disease pathogenesis;
      others remain identified only as anonymous "loci" implicated by linkage analyses.
      The greater understanding of genetic mechanisms serves to enable not only studies
      of gene effects in pathogenesis, but also the influence of various environmental
      factors that may modify the effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8521946
TI  - Epidemiology of tobacco use and dependence.
AB  - Knowledge of the epidemiology of tobacco use and dependence can be used to guide
      research initiatives, intervention programs, and policy decisions. Both the
      reduction in the prevalence of smoking among US adults and black adolescents and
      the decline in per capita consumption are encouraging. These changes have
      probably been influenced by factors operating at the individual (e.g., school
      based prevention programs and cessation programs) and environmental (e.g., mass
      media educational strategies, the presence of smoke-free laws and policies, and
      the price of tobacco products) levels (for a discussion of these factors, see,
      e.g., refs. 2, 48, 52, 183, and 184). The lack of progress among adolescents,
      especially whites and males, and the high risk for experimenters of developing
      tobacco dependence present cause for great concern (48, 183-186). In addition to
      those discussed above, several areas of research can be recommended. 1. Better
      understanding of the clustering of tobacco use with the use of other drugs, other
      risk behaviors, and other psychiatric disorders could better illuminate the
      causal processes involved, as well as the special features of the interventions
      needed to prevent and treat tobacco dependence. 2. To better understand
      population needs, trend analyses of prevalence, initiation, and cessation should,
      whenever possible, incorporate standardized measures of these other risk factors.
      Future research should compare the effect of socioeconomic status variables on
      measures of smoking behavior among racial/ethnic groups in the United States. 3.
      For reasons that may be genetic, environmental, or both, some persons do not
      progress beyond initial experimentation with tobacco use (2, 48, 183, 187-192),
      but about one-third to one-half of those who experiment with cigarettes become
      regular users (48, 193, 194). Factors, both individual and environmental, that
      can influence the susceptibility of individuals to tobacco dependence need
      further attention. 4. To estimate their sensitivity and specificity, comparisons
      of the National Household Survey on Drug Abuse indicators of dependence with DSM
      based criteria are needed. Public health action continues to be warranted to
      reduce the substantial morbidity and mortality caused by tobacco use (195). A
      paradigm for such action has been recommended and involves preventing the onset
      of use, treating tobacco dependence, protecting non-smokers from exposure to
      secondhand smoke, promoting nonsmoking messages while limiting the effect of
      tobacco advertising and promotion on young people, increasing the real (inflation
      adjusted) price of tobacco products, and regulating tobacco products (186).

PMID- 8521947
TI  - Heroin epidemics revisited.
AB  - This paper reviewed heroin use data from the US government's epidemiologic
      monitoring system for substance abuse. The monitoring system has multiple
      components, i.e., the Drug Abuse Warning Network of reporting emergency rooms
      (9), annual surveys of high school and post-high school youth (3, 4), annual
      National Household Surveys of Substance Abuse (7, 8, 50), Drug Use Forecasting
      (51), the Community Epidemiology Work Group (52), and law enforcement systems not
      reviewed here. These monitoring systems should identify any major increase in
      heroin incidence in this country relatively early. This is important, because the
      early stages of heroin epidemics are often hidden from society, and the epidemics
      are already full-blown by the time health and other agencies become aware of the
      size of the affected population and are required to respond. The hidden or
      underground nature of heroin epidemics is caused by 1) the need of each user to
      hide an illegal activity and 2) the delay between the time when heroin is first
      used and the onset of physical dependence and other adverse consequences, which
      bring new heroin addicts to the attention of treatment and enforcement systems.
      Despite an epidemiologic surveillance system which should rapidly identify large
      scale heroin spread in this country, our treatment and law enforcement systems
      are not organized to respond rapidly to contain an epidemic. Substance abuse
      treatment services are not structured for rapid expansion and contraction based
      on fluctuating need. Apart from HIV prevention programs, we do not have outreach
      teams attached to treatment programs that could quickly identify local outbreaks
      and involve new heroin abusers in treatment (10).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8521948
TI  - Developmental epidemiology.

PMID- 8521949
TI  - Epidemiology of mental disorders in middle age and late life: conceptual issues.
AB  - One of the "uses of epidemiology" described by Morris (1) is to complete the
      clinical picture in describing the natural history of disease. This arena for
      epidemiologic inquiry is especially important in relation to psychiatric
      disturbances. Most adults with psychiatric complaints and symptoms, especially
      older adults, do not receive care in the mental health sector (2-4). Distorted
      views of the nature of these disturbances can result when studies sample only
      from those individuals who are treated by psychiatrists or other specialists (5,
      6). This has led to greater interest in previously neglected venues such as
      nursing homes, home care, and the primary health care services (7-12). Improved
      detection and treatment of mental disturbances in primary health care may be an
      essential key to enhance the effectiveness of community treatment (13).
      Completing the clinical picture is a critical task indeed. The purpose of this
      review is to introduce several conceptual issues important to completion of the
      clinical picture in epidemiologic research on risk and protective factors for
      mental disorders across the life course, with a focus on adulthood and late life.
      These issues are 1) the measurement of psychiatric disturbances in populations,
      2) methodological considerations in surveys of older adults, and 3) the life
      course perspective on risk factors for psychiatric disturbances.

PMID- 8521950
TI  - Psychiatric sequelae of low birth weight.

PMID- 8521951
TI  - 1H NMR of albumin in human blood plasma: drug binding and redox reactions at
      Cys34.
AB  - 1H NMR methods are described which allow direct studies of the Cys34 binding site
      of albumin in intact human blood plasma in vitro. Antiarthritic gold drugs and
      the alcohol-aversive drug disulfiram induce a structural transition detectable
      via H epsilon 1 and H delta 2 resonances of His3 of albumin, and reactions of
      cystine, glutathione and captopril in plasma have also been investigated.
      Contrary to most assumptions, little of the albumin in normal plasma appears to
      be blocked at Cys34 as a cystine disulfide.

PMID- 8521952
TI  - Cre1, the carbon catabolite repressor protein from Trichoderma reesei.
AB  - In order to investigate the mechanism of carbon catabolite repression in the
      industrially important fungus Trichoderma reesei, degenerated PCR-primers were
      designed to amplify a 0.7-bp fragment of the cre1 gene, which was used to clone
      the entire gene. It encodes a 402-amino acid protein with a calculated M(r) of
      43.6 kDa. Its aa-sequence shows 55.6% and 54.7% overall similarity to the
      corresponding genes of Aspergillus nidulans and A. niger, respectively.
      Similarity was restricted to the aa-region containing the C2H2 zinc finger and
      several aa-regions rich in proline and basic amino acids, which may be involved
      in the interaction with other proteins. Another aa-region rich in the SPXX-motif
      that has been considered analogous to a region of yeast RGR1p, was instead
      identified as a domain occurring in several eucaryotic transcription factors. The
      presence of the cre1 translation product was demonstrated with polyclonal
      antibodies against Cre1, which identified a protein of 43 (+/- 2) kDa in cell
      free extracts from T. reesei. A Cre1 protein fragment from the two zinc fingers
      to the region similar to the aa-sequence of eucaryotic transcription factors, was
      expressed in Escherichia coli as a fusion protein with glutathione S-transferase.
      EMSA and in vitro footprinting revealed binding of the fusion protein to the
      sequence 5'-GCGGAG-3', which matches well with the A. nidulans consensus sequence
      for CreA binding (5'-SYGGRG-3'). Cell-free extracts of T. reesei formed different
      complexes with DNA-fragments carrying this binding sites, and the presence of
      Cre1 and additional proteins in these complexes was demonstrated. We conclude
      that T. reesei Cre1 is the functional homologue of Aspergillus CreA and that it
      binds to its target sequence probably as a protein complex.

PMID- 8521953
TI  - M-caveolin, a muscle-specific caveolin-related protein.
AB  - Caveolae, small invaginations of the plasma membrane, are a characteristic
      feature of many mammalian cells. The best-characterised caveolar protein is the
      integral membrane protein, VIP21-caveolin. We now describe a novel homologue of
      VIP21-caveolin, M-caveolin, which is expressed exclusively in muscle. M-caveolin
      was shown to be expressed in differentiated myotubes but not myoblasts. Epitope
      tagged M-caveolin expressed in non-muscle cells was targetted to surface caveolae
      where it colocalized with endogenous VIP21-caveolin. M-caveolin may play a
      specialised role in the caveolae of muscle cells.

PMID- 8521954
TI  - Agonist regulation of the expression of the delta opioid receptor in NG108-15
      cells.
AB  - Exposure of neuronal cells to the chronic presence of opiates leads to a complex
      series of biochemical events which reflect the changes that result in tolerance
      and dependence in animals. To achieve a better understanding of the molecular
      mechanisms underlying these processes, we have examined the effect of agonist
      efficacy on the regulation of the delta-opioid receptor mRNA in NG108-15 cells.
      Incubation with various opiates decreased receptor numbers in the order of their
      efficacy. Northern blot analysis showed that there are 4 size classes of mRNA
      coding for the delta-opioid receptor in NG108-15 cells even though only one known
      protein species is found. Moreover, the amount of each transcript is coordinately
      decreased by long-term etorphine treatment, but not necessarily to the same
      extent. The etorphine-induced decrease in receptor mRNA was found to be slow in
      onset, whereas a much more rapid loss of receptor number was observed. This
      disparity suggests that the down-regulation induced by etorphine can occur both
      at the levels of receptor protein modification and receptor gene expression, and
      that the mechanisms of the two processes may be different.

PMID- 8521955
TI  - Nucleotide induced conformation determines posttranslational isoprenylation of
      the ras related rab6 protein in insect cells.
AB  - Small GTP binding proteins of the rab/YPT family are essential regulators of
      vectorial transport in the eukaryotic cell. Members of the rab/YPT1 family are
      found on the cytoplasmic surface of distinct intracellular membrane compartments.
      Membrane attachment is facilitated by a C-terminal geranylgeranyl moiety. In this
      report we investigated posttranslational modification and membrane binding of the
      rab6 protein, a member of the rab/YPT family located on the Golgi apparatus. A
      set of point mutations, which simulate the GDP or GTP bound conformation, was
      introduced into the rab6 cDNA. The mutated cDNAs were expressed in insect cells
      and the ability of the protein products to undergo geranylgeranyl modification
      and membrane association was assessed by Triton X-114 partition and cell
      fractionation. We report here that the modification of rab6 in insect cells
      depends on protein conformation. Only the GDP bound form, but not the GTP bound
      form is isoprenylated and subsequently membrane bound.

PMID- 8521956
TI  - Identification of regulatory proteins that might be involved in carbon catabolite
      repression of the aminopeptidase I gene of the yeast Saccharomyces cerevisiae.
AB  - Transcription of the vacuolar aminopeptidase yscI (APE1) gene in Saccharomyces
      cerevisiae has previously been suggested to require the participation of a cis
      upstream activation sequence (UAS) involved in carbon catabolite repression that
      responds to glucose. To determine the structure of the APE1 UAS element, we used
      the 18-bp sequence 5'-ATGAATTAGTCAGCTTCT-3' as the DNA-binding site. Using gel
      mobility shift assays, we have identified a 78 kDa protein from yeast that binds
      specifically to both single and double-stranded forms of the UAS DNA-binding
      site. We have also identified a 48 kDa heterodimer from yeast that binds
      specifically to the single-stranded form of the UAS and whose DNA binding
      activity is remarkably heat stable. Even though the APE1 UAS contains a consensus
      sequence for the binding of the yeast activator protein yAP1, the two DNA-protein
      complexes could still be detected in a strain bearing a deletion in the YAP1
      gene.

PMID- 8521957
TI  - mtDNA-depleted U937 cells are sensitive to TNF and Fas-mediated cytotoxicity.
AB  - It has been proposed that TNF cytotoxicity is mediated by reactive oxygen
      intermediates generated by uncoupling of mitochondrial respiration. We have
      compared sensitive U937 cells and derived cell lines depleted of mtDNA for their
      ability to undergo TNF- and Fas-induced apoptosis. Cells lacking around 98% of
      mtDNA were still sensitive to TNF-induced apoptosis. U937 cells devoid of mtDNA
      (U937-rho degree) were resistant to TNF, but this was due to the loss of its 55
      kDa receptor. U937-rho degree cells were also resistant to docosahexaenoic acid,
      which causes U937 cell death by lipid peroxidation. These cells were sensitive to
      anti-Fas toxicity. The results indicate that TNF and Fas-induced toxicity occurs
      by a mechanism mostly independent of mitochondrial free radical generation.

PMID- 8521958
TI  - Characterisation of the RANTES/MIP-1 alpha receptor (CC CKR-1) stably transfected
      in HEK 293 cells and the recombinant ligands.
AB  - The CC chemokines RANTES and MIP-1 alpha are known to activate certain leucocytes
      and leucocytic cell lines. We have produced and fully characterised the
      recombinant proteins expressed in E. coli. They induce chemotaxis of the pro
      monocytic cell line, THP-1 and T cells. THP-1 cells express three of the known CC
      chemokine receptors. In order to study the activation of a single receptor, we
      have expressed the shared receptor (CC CKR-1) for RANTES and MIP-1 alpha stably
      in the HEK 293 cell line. We have examined the effects of RANTES and MIP-1 alpha
      on the CC CKR-1 transfectants by equilibrium binding studies and in a chemotaxis
      assay. RANTES competes for [125I]RANTES with an IC50 of 0.6 +/- 0.23 nM, whereas
      MIP-1 alpha competes for its radiolabelled counterpart with an IC50 of 10 +/- 1.6
      nM in the transfectants. These affinities are the same as those measured on the
      THP-1 cell line. The stably transfected HEK 293 cells respond to both these
      chemokines in the chemotaxis assay with the same EC50 values as those measured
      for THP-1 cells. This indicates that this cellular response can be mediated
      through the CC CKR-1 receptor.

PMID- 8521959
TI  - TNF alpha receptor expression in rat cardiac myocytes: TNF alpha inhibition of L
      type Ca2+ current and Ca2+ transients.
AB  - Tumor necrosis factor-alpha (TNF alpha) is a potentially powerful anti-neoplastic
      agent; however, its therapeutic usefulness is limited by its cardiotoxic and
      negative inotropic effects. Accordingly, studies were undertaken to gain a better
      understanding of the mechanisms of TNF alpha-mediated cardiodepression. Single
      cell RT-PCR, [125I]TNF alpha ligand binding and Western immunoblotting
      experiments demonstrated that rat cardiac cells predominantly express type I TNF
      alpha receptors (TNFRI or p60). TNF alpha inhibited cardiac L-type Ca2+ channel
      current (ICa) and contractile Ca2+ transients. Thus, it is possible that the
      negative inotropic effects of TNF alpha are the result of TNFRI-mediated blockade
      of cardiac excitation-contraction coupling.

PMID- 8521960
TI  - Extracellular domain of type I receptor for transforming growth factor-beta:
      molecular modelling using protectin (CD59) as a template.
AB  - We have observed that the extracellular domain of T beta RI and protectin (CD59),
      an inhibitor of the membrane attack complex of complement, share structural
      features, a distinct spacing of ten cysteines and a C-terminal 'Cys-box'. Based
      on these common features and the recently determined NMR-structure of protectin,
      a three-dimensional model for the extracellular domain of T beta RI was
      constructed. After energy minimization and molecular dynamics simulation, a
      structure with four extending fingers (pes quattvordigitorum) and two clusters of
      charged residues was obtained. This model provides a view to the understanding of
      interactions between T beta RI, T beta RII and TGF beta during ligand recognition
      and signal transduction.

PMID- 8521961
TI  - Secretion of laminin alpha 2 chain in cerebrospinal fluid.
AB  - The absence of laminin alpha 2 chain causes muscle cell degeneration and
      peripheral dysmyelination in congenital muscular dystrophy patients and dy mice,
      suggesting its role in the maintenance of sarcolemmal architecture and peripheral
      myelinogenesis. Here we demonstrate the secretion of laminin alpha 2 chain in
      cerebrospinal fluid (CSF). Laminin alpha 2 chain was detected as a minor
      component of the total CSF proteins or glycoproteins. Laminin alpha 2 chain was
      localized in the cytoplasm of epithelial cells of choroid plexus, suggesting
      active secretion. Our results suggest that immunochemical analysis of CSF laminin
      alpha 2 chain could be useful as an aid for the diagnosis of congenital muscular
      dystrophy.

PMID- 8521962
TI  - Molecular characterization of two forms of nontoxic-nonhemagglutinin components
      of Clostridium botulinum type A progenitor toxins.
AB  - The entire sequences of the type A nontoxic-nonhemagglutinin gene and an adjacent
      open reading frame designated as orf 22-a, which are located between the
      neurotoxin and the HA-35 genes were determined. SDS-PAGE and N-terminal amino
      acid sequence analyses of the purified type A progenitor toxins (12S, 16S and
      19S) indicate that the nontoxic-nonhemagglutinins of 16S and 19S are single
      peptides of approximately 120k, but that of 12S has a cleavage at the site
      between Pro-144 and Phe-145 of this protein.

PMID- 8521963
TI  - FAD is a further essential cofactor of the NAD(P)H and O2-dependent zeaxanthin
      epoxidase.
AB  - In chloroplasts of plants the xanthophyll cycle is suggested to function as a
      protection mechanism against photodamage. Two enzymes catalyze this cycle. One of
      them, violaxanthin de-epoxidase, transforms violaxanthin (Vio) to zeaxanthin
      (Zea) via antheraxanthin (Anth) and is bound to the lumenal surface of the
      thylakoid vesicles, when being in its active state. The other enzyme, Zea
      epoxidase, is responsible for the backward reaction (Zea-->Anth-->Vio) and is
      active at the stromal side of the thylakoid. For the epoxidation of Zea this
      enzyme requires NAD(P)H and O2 as cosubstrates. Using isolated thylakoid
      membranes we found that FAD enhances the epoxidase activity (decrease of apparent
      Km for NAD(P)H and two-fold increase of Vmax). The flavin functions as a third
      cofactor which is partially lost during the isolation procedure of thylakoids.
      Other flavins, such as FMN or riboflavin are without effect. The involvement of
      FAD in the enzymatic reaction is also demonstrated by the inhibitory action of
      diphenyleneiodoniumchloride (DPI) (IC50 = 2.3 microM), a compound that blocks the
      reoxidation of reduced flavins within enzymes. The Zea-epoxidase is a multi
      component enzyme system which can be classified as FAD-containing, NAD(P)H- and
      O2-dependent monooxygenase that is able to epoxidize 3-hydroxy beta-ionone rings
      of xanthophylls in the 5,6 position.

PMID- 8521964
TI  - Dynamic light scattering study of the two-domain structure of Humicola insolens
      endoglucanase V.
AB  - Endoglucanase V (EG V) of HUmicola insolens is composed of a catalytic domain and
      of a cellulose-binding domain linked by a 33 amino acid long peptide rich in Ser,
      Thr and Pro residues. This work describes the dynamic behavior of the two-domain
      structure of EG V as revealed by quasi-elastic light scattering experiments. For
      both the full-length and the isolated catalytic domain, the autocorrelation
      function is essentially described by a single relaxation mode. The equivalent
      hydrodynamic radius of the catalytic domain was found to correspond precisely to
      the dimensions measured from the previously determined three-dimensional
      structure. The results obtained with the full-length protein allow a description
      of the two domain structure of EG V similar to that resulting from earlier
      studies using small angle X-ray scattering on cellulases from Trichoderma reesei.
      The hydrodynamic dimensions of the entire enzyme can be approximated as an
      ellipsoid with dimensions of 42 x 133.6 A.

PMID- 8521965
TI  - Identification of the Zn2+ binding region in calreticulin.
AB  - Calreticulin binds Zn2+ with the relatively high affinity/low capacity. To
      determine the location of the Zn2+ binding site in calreticulin different domains
      of the protein were expressed in E. coli, using the glutathione S-transferase
      fusion protein system, and their Zn(2+)-dependent interaction with Zn(2+)-IDA
      agarose were determined. Three distinct domains were used in this study: the N +
      P-domain (the first 290 residues); the N-domain (residues 1-182) and the proline
      rich P-domain (residues 180-273). The N + P-domain bound to the Zn(2+)-IDA
      agarose and were eluted with an increasing concentration of imidazole. The N
      domain also bound 65Zn2+ as measured by the overlay method. The P-domain did not
      interact with the Zn(2+)-IDA-agarose and it did not bind any detectable amount of
      Zn2+. Chemical modification of calreticulin with diethyl pyrocarbonate indicated
      that five out of seven histidines were protected in the presence of Zn2+ but they
      were modified by diethyl pyrocarbonate in the absence of Zn2+ suggesting that
      these residues may be involved in Zn2+ binding to calreticulin. We conclude that
      Zn2+ binding sites in calreticulin are localized to the N-domain of the protein,
      region that is not involved in Ca2+ binding to calreticulin.

PMID- 8521966
TI  - Binding of vanadium (IV) to the phosphatase calcineurin.
AB  - X-band electron spin resonance spectroscopy was used to study the binding of
      vanadium (IV), or vanadyl, to the brain serine/threonine phosphatase-2B,
      calcineurin. Spectra were determined on frozen solutions of vanadyl and
      calcineurin at pH 7.4 in the presence of 20% (v/v) glycerol. The binding of
      vanadyl to the enzyme was established, and the data suggested the presence of two
      classes of sites, the higher affinity class of which contained two binding sites
      for vanadyl. The calcium-binding B subunit of the heterodimeric protein was also
      shown to bind vanadyl. The holoprotein appeared to be stabilized by vanadyl, and
      vanadyl enhanced enzymatic activity when assayed with or without calmodulin in
      the absence of calcium.

PMID- 8521967
TI  - A recombinant polypeptide, composed of the alpha-helical neck region and the
      carbohydrate recognition domain of conglutinin, self-associates to give a
      functionally intact homotrimer.
AB  - A recombinant polypeptide composed of the alpha-helical neck region and
      carbohydrate recognition domain (CRD) of bovine conglutinin was expressed in
      Escherichia coli. The recombinant protein formed inclusion bodies but could be
      solubilised using a denaturation-renaturation cycle based on urea and then
      purified by affinity chromatography on a TSK-N-acetylglucosamide column. The
      purified product behaved as a homotrimer in non-dissociating conditions, with
      three CRDs held together by the alpha-helical neck regions. The trimer, although
      lacking the N-terminal and collagen regions of the native conglutinin, showed the
      same binding carbohydrate specificities as the native molecule, for the
      complement fragment C3b and for lipopolysaccharides derived from Gram-negative
      bacteria.

PMID- 8521968
TI  - beta-Glucosylarginine: a new glucose-protein bond in a self-glucosylating protein
      from sweet corn.
AB  - In the search for a protein primer for starch synthesis, an autocatalytic self
      glucosylating protein has been isolated from sweet corn. Several tryptic peptides
      were obtained from the [14C]glucosylated protein and were sequenced,
      corresponding to over 40% of the estimated total sequence (molecular mass 42
      kDa). There is no homology with the amino acid sequence of the autocatalytic
      glycogen primer, glycogenin, nor in respect of the nature of the union between
      the autocatalytically added glucose and the protein, which, in the case of the
      corn protein, now named amylogenin, is a novel glucose-protein bond, a single
      beta-glucose residue joined to an arginine residue.

PMID- 8521969
TI  - Endotoxin and fibrinogen degradation product-D have different actions on
      carbohydrate metabolism: role of Kupffer cells.
AB  - The effect of endotoxin-derived lipopolysaccharide (LPS) and fibrinogen
      degradation product D (FDPD) on oxygen consumption and glycogenolysis in the
      perfused rat liver was investigated. 1. Infusion of LPS (100 micrograms/ml) or
      FDPD (7 micrograms/ml) caused a rapid stimulation of oxygen uptake by the
      perfused liver of 10-12 mumol/g/h. 2. LPS also caused a transient increase in
      glucose and lactate release into the perfusion medium from endogenous glycogen;
      however, FDPD was without effect. 3. Destruction of Kupffer cells by GdCl3
      pretreatment blocked the effects of LPS and FDPD on oxygen uptake and
      glycogenolysis. Further, LPS and FDPD had no effect on oxygen consumption by
      isolated hepatocytes. Therefore, it is concluded that Kupffer cells are involved
      in the increase of hepatic oxygen consumption and carbohydrate release caused by
      LPS, most likely via release of PGE2 and PGD2. Since FDPD increased oxygen but
      not carbohydrate release, it is concluded that it acts via stimulating the
      release of mediators distinct from those released following LPS infusion.

PMID- 8521970
TI  - Expression of an archaeal chaperonin in E. coli: formation of homo- (alpha, beta)
      and hetero-oligomeric (alpha+beta) thermosome complexes.
AB  - Co-expression of the two genes encoding the alpha- and beta-subunit of the
      Thermoplasma acidophilum thermosome in Escherichia coli yielded fully assembled
      hetero-oligomeric complexes (alpha+beta). Surprisingly, also separate expression
      of both genes resulted in formation of hexadecameric complexes (alpha, beta) in
      the bacterial cytoplasm. On electron micrographs these complexes were
      indistinguishable from each other and from the native thermosome. The recombinant
      alpha-complex as well as the native thermosome could be reconstituted in vitro
      from their dissociated subunits in the presence of Mg-ATP.

PMID- 8521971
TI  - Wortmannin inhibits transcytosis of dimeric IgA by the polymeric immunoglobulin
      receptor.
AB  - Phosphatidyl inositol 3-kinase (PI3K) plays an essential role in numerous
      signaling events, and increasingly has been implicated in regulation of certain
      membrane traffic events. The polymeric immunoglobulin receptor (pIgR)
      transcytoses dimeric IgA (dIgA) across epithelial cells and into external
      secretions, where the dIgA forms the first specific immunological defense against
      infection. We show here that wortmannin, a highly specific inhibitor of PI3K,
      inhibits transcytosis of dIgA by the pIgR. Instead, the dIgA is recycled back to
      the basolateral surface of the epithelial cell. PI3K therefore plays an essential
      role in regulating the transcytosis of dIgA, a key step in the mucosal immune
      response.

PMID- 8521972
TI  - Lateral mobility of Fc gamma RIIa is reduced by protein kinase C activation.
AB  - The lateral mobility of membrane proteins can reflect the extent of various
      protein-protein interactions. Using the fluorescence recovery after
      photobleaching technique, we have studied the lateral mobility of human Fc gamma
      RIIa and some Fc gamma RIIa mutants expressed in either P388D1 cells, a mouse
      macrophage-like cell line, or in Chinese hamster ovary (CHO) cells [1]. After
      treatment with phorbol myristate acetate (PMA), only the Fc gamma RIIa molecules
      capable of mediating rapid endocytosis of immune complexes exhibited a reduced
      lateral diffusion coefficient with respect to untreated controls. Wild type Fc
      gamma RIIa expressed in CHO cells, and nonfunctional Fc gamma RIIa mutants
      expressed in P388D1 cells did not show any differences upon PMA treatment. This
      finding suggests that protein kinase C activation evokes additional protein
      protein interactions with the cytoplasmic domain of functional Fc gamma RIIa,
      which reduced receptor lateral mobility. The identity of these putative
      interacting proteins and the nature of the interactions remain to be elucidated.

PMID- 8521973
TI  - Characterisation of an Arabidopsis thaliana cDNA encoding glutathione synthetase.
AB  - An Arabidopsis thaliana cDNA (AtGSHS) encoding a protein with high primary
      sequence identity to cDNAs previously isolated from Xenopus laevis (42%),
      Schizosaccharomyces pombe (40%), Rattus norvegicus (40%) and Homo sapiens (37%)
      encoding glutathione synthetase (EC 6.3.2.3) has been isolated by functional
      complementation of an Escherichia coli mutant deficient in this enzyme. AtGSHS is
      encoded by a single gene, GSHB, as determined by Southern blot analysis and the
      corresponding mRNA is abundant in both roots and leaves of Arabidopsis.

PMID- 8521974
TI  - N-myristoylation of recoverin enhances its efficiency as an inhibitor of
      rhodopsin kinase.
AB  - Recoverin, a recently identified member of the EF-hand superfamily of Ca(2+)
      binding proteins, is capable to inhibit rhodopsin phosphorylation by rhodopsin
      kinase at high but not at low free [Ca2+]. The N-terminal glycine residue of
      retinal recoverin is heterogeneously acylated with myristoyl or related N-acyl
      group. To clarify the role of the N-terminal acylation of recoverin in its
      inhibitory action upon rhodopsin phosphorylation, we compared the efficiency of
      myristoylated and non-myristoylated forms of recombinant recoverin as inhibitors
      of rhodopsin kinase activity. We have found that rhodopsin phosphorylation by
      purified rhodopsin kinase, which does not depend on free [Ca2+] in the absence of
      recoverin, is regulated by Ca2+ in the presence of both forms of the recombinant
      protein. EC50 values for Ca2+ are the same (2 microM) for the myristoylated and
      non-myristoylated forms; the Hill coefficients of 1.7 and 0.9, respectively,
      indicate that the effect is cooperative with respect to Ca2+ only for
      myristoylated recoverin. In the presence of Ca2+, both forms of recoverin taken
      at saturated concentrations cause an almost equal inhibition of rhodopsin
      phosphorylation. However, the inhibitory action of the myristoylated form occurs
      at much lower its concentrations than that of the non-myristoylated form (EC50
      are 0.9 and 6.5 microM, respectively).

PMID- 8521975
TI  - Automation of micro-preparation and enzymatic cleavage of gel electrophoretically
      separated proteins.
AB  - To achieve high throughput, protein microcharacterization sample preparation must
      be automated. We describe a cartesian robot capable of processing 32 protein
      samples in parallel. The system is based on specially designed flow-through
      reactors for contamination-free reagent delivery and removal. Washing of excised
      gel pieces, reduction and alkylation, proteolytic cleavage and peptide extraction
      are performed in these reactors. Compatibility of the system with HPLC peptide
      separation and Edman degradation as well as with laser desorption mass
      spectrometry of the unseparated mixture is demonstrated. This is the first report
      describing automated preparation and processing of multiple protein samples.

PMID- 8521976
TI  - Circumvention of multidrug resistance in neoplastic cells through scavenger
      receptor mediated drug delivery.
AB  - A conjugate of the antineoplastic drug daunomycin (DNM) with maleylated bovine
      serum albumin (MBSA-DNM) was taken up with high efficiency by a multidrug
      resistant variant, JD100, of the murine-macrophage tumour cell line, J774A.1,
      through the scavenger receptors resulting in cessation of DNA synthesis. In
      contrast, free DNM at similar concentrations did not affect the incorporation of
      [3H]thymidine by these cells. These results suggest that receptor-mediated
      intracellular delivery of antineoplastic drugs could be a viable and new approach
      for overcoming the problem of multidrug resistance in chemotherapy of neoplastic
      diseases.

PMID- 8521977
TI  - Transcriptional regulation of apolipoprotein A-I expression in Hep G2 cells by
      phorbol ester.
AB  - The regulation of apolipoprotein A-I (apo A-I) gene expression by 12-O
      tetradecanoylphorbol 13-acetate (TPA) was investigated in the human hepatoma cell
      line Hep G2. TPA treatment decreased apo A-I mRNA levels in a time-dependent
      manner, by up to 50% versus control cells within 24 h. Nuclear run-on
      transcription assays demonstrated a transcriptional effect of TPA. Using
      transfection analysis with a plasmid construct containing the -1378/+11 apo A-I
      promoter fused to the secreted placental alkaline phosphatase (SPAP) reporter
      gene, we showed that the SPAP activity was decreased to 50% when Hep G2 cells
      were incubated in the presence of TPA. The inhibitory effect of TPA was still
      maintained when fragment -253 to -4 of apo A-I promoter was linked to the CAT
      reporter gene. These data indicate that transcriptional modulation of
      apolipoprotein A-I gene expression following phorbol ester treatment is
      transduced by gene elements located between -253 and -4 of the apo A-I promoter.

PMID- 8521978
TI  - [The effect of a phorbol ester on the aortic wall].
AB  - Changes in the muscle tissue stiffness are important and necessary signs of the
      contractile process. The work is devoted to the study of this parameter of the
      smooth muscle tissue reaction during the action of phorbol esters, (namely,
      phorbol 12-myristate 13-acetate (PMA)), synthetic imitators of diacylglycerole.
      The experiments were carried out on isolated native preparations of aorta
      thoracic area of guinea pig under isometric conditions. Contraction induced by
      PMA or by the temperature was not accompanied by the stiffness changes. Potassium
      contraction (its development, amplitude, relaxation) evoked on the plateau of the
      PMA-induced contraction was similar in all respects to that in control: the
      stiffness increased significantly. These findings prove independent development
      of these two types of contractile processes. At the same time, the stiffness
      invariability and similar ratios of optical density to mechanical strength
      changes in the contractions induced by PMA action or by temperature show the
      likeness of the force generation mechanisms in these mechano-chemical reactions.
      The results obtained cannot be explained in terms of the generally accepted
      hypothesis of actomyosin interaction. The conclusion is made that phorbolic
      esters during the action on the smooth muscle tissue activate the mechanical
      strength generation by the connective tissue matrix.

PMID- 8521979
TI  - [The function of the reproductive system in x-ray-irradiated male rats after the
      transplantation of a culture of testicular cells from newborn piglets].
AB  - The effect exerted by transplantation of the 5 day culture of testicles from
      newly born piglets on the hypogonadal state of mature X-ray irradiated (3 Gy)
      rats was studied. It has been found that a month after transplantation (two
      months after irradiation) the hypogonadal state disappeared for a while, which is
      confirmed by normalization of the weight of seminal vesicles, content of
      testosterone and biologically active lutropine, restoration of the reproductive
      function of rats. No significant changes in steroidogenesis activity have been
      found, which proves a substituent character of transplantation. The effect
      disappears three months later but certain restoration of the content of nucleic
      acids in the testicles is observed.

PMID- 8521980
TI  - [Reactive hyperemia in vibration-induced disease].
AB  - The study of a blood flow in the forearm of patients with vibration disease has
      shown its significant lowering accompanied by an increase in vascular resistance
      in this region. Reactive hyperemia in the forearm vessels of these patients was
      diminished significantly, which shows decrease in the vasodilatation reserve
      induced by disturbances in functional activity of the endothelium. These
      disturbances are probably manifested in decrease of production of vasodilatation
      factors. Reactive hyperemia may be used to determine the endothelium dysfunctions
      caused by action of different pathogenic factors.

PMID- 8521981
TI  - [Lipid peroxidation and antioxidant system activity in the brain, stomach and
      heart tissues and blood serum of rats under stress].
AB  - Changes in the level of peroxide oxygenation of lipids and activity of the
      antioxygenative system in tissues of the brain, stomach, heart and blood serum
      were studied in experiments on rats [correction of mice] when modelling
      immobilization stress and emotion-pain stress of waiting. The balance disturbance
      in favour of activation of free radical processes in all investigated tissues was
      observed with maximal changes in the brain and minimal ones in the stomach
      tissues. More sensitive changes were observed under conditions of emotion and
      pain waiting stress.

PMID- 8521982
TI  - [The characteristics of the protein and lipid metabolic indices of poultry
      farmers with extrinsic allergic alveolitis].
AB  - The content of albumins, globulin fractions and cholesterol was studied in blood
      serum of poultry breeders with exogenic allergic alveolitis (EAA) having
      different service terms. Breeders suffering from EAA with service term of 1-20
      years show a decrease in the albumin content and an increase in globulin
      fractions and cholesterol in blood which may indicate liver disturbances and
      hypercholesterolemia.

PMID- 8521983
TI  - [The functional organization of the adaptive and compensatory reactions of the
      endocrine glands].
AB  - Current concepts of the systemic organization and interrelationship between
      adaptive and compensatory responses of the endocrine glands and hormone-producing
      cells are reviewed. Emphasis is made on the involvement of prolactin, insulin
      endorphins and other neuropeptides into stress responses. A problem of the
      multihormonal control of physiological functions and role of blood protein
      carriers and hormonal cytoreceptors in pathogenesis of various diseases are
      discussed. Special attention is paid to the importance of endocrine function
      reserves testing for diagnosis of premorbid states and for estimation of human
      psychophysiological and physical potentials.

PMID- 8521984
TI  - [A pharmacological analysis of the effect of angiotensin on stimulated gastric
      secretion].
AB  - Chronic experiments on dogs with gastric fistulas were carried out to study the
      influence of angiotensin 1 and angiotensin 2 on pentagastrin- and histamine
      induced gastric acid secretion. It was established that both angiotensins
      inhibited gastric acid secretion stimulated by pentagastrin but not by histamine.
      Comparative analysis of the effects of stimulation and inhibition of cholino- and
      adrenoreceptors on this inhibitory action of angiotensins suggested the mediation
      of angiotensin influence through the modulation of cholinergic reactions of
      parietal cells in the stomach.

PMID- 8521985
TI  - [The effect of adenosine on the hypothalamo-hypophyseal-adrenal system].
AB  - The effect of various doses of intraperitoneally administered adenosine on the
      content of corticotropin and corticosteroids on the blood plasma was studied in
      Wistar rats. Dependence of the effect exerted by adenosine on the hypothalamo
      pituitary-adrenal system on its dose was demonstrated: 1 hour after nucleoside
      administration in a dose of 50 mg/kg corticotropin concentration increased; 1
      hour after adenosine administration in a dose of 25 mg/kg the level of
      corticosteroids in the blood plasma decreased.

PMID- 8521986
TI  - [The characteristics of the development of neurodynamic functions in young
      schoolchildren].
AB  - The fast increase of neurodynamic functional parameters, absence of marked
      differences in mean senses of individual values of impellent reactions in
      candidates with different properties of nervous processes, and connection between
      individual typological peculiarities of high nervous activity and latent periods
      of complex sensorimotor reactions were stated in the same children of early
      school age (6-10 years) examined during three years.

PMID- 8521987
TI  - [The role of the basolateral nuclei of the rat amygdala in organizing rapid food
      acquisition movements].
AB  - The influence of electrolytic destruction of the basolateral nucleus of amygdala
      (BLA) on rapid food-getting movements was studied in albino rats. After one side
      destruction of the BLA, contralateral to the working forelimb it was found that
      the number of movements and their frequency decreased with an increase of their
      duration. After two side destruction of the BLA the number of movements increased
      with a decrease of their frequency. Duration of movements was unstable. After the
      BLA destruction (especially two side) all parameters were unstable both each day
      and during each experiment. Different level and character of the compensation
      after one- and two side destruction of the BLA was observed. The conclusion is
      made about the activating, stabilizing and training influences of the BLA on the
      rapid food-getting movements in rats.

PMID- 8521988
TI  - [The complexity of the information load, the functional status and the efficiency
      of operator activities].
AB  - Experimental data permit stating that in a wide range of functional state
      modelled pharmacologically with the use of aminazine, caffeine under conditions
      of a thrusting tempo of the work an increase in the volume of information
      presented has induced a decrease in speed, quality and productivity of operator's
      labour; an increase in tempo of information supply has led to a rise of speed and
      fall of information processing quality, changes in the labour productivity are
      subjects to the low of the optimum. It is shown that significance of the
      functional state for efficient operator's activity grows with complexity of the
      information load.

PMID- 8521989
TI  - [The structural-functional characteristics of the blood vessels of the testis and
      its tunicae].
AB  - The structure of arteries and veins of a testis and its capsules was studied on
      53 preparations of human testes (men aged from 25 to 30 years) and on 43
      preparations of rat testes (mature Wistar rats weighing 150-200 g) using the
      methods of vessels' injection, angiography, morphometry and silver impregnation.
      It has been ascertained that structure of testicular capsule arteries, veins and
      microvessels has specific features. The role of these blood vessels in
      thermoregulation of testis is discussed.

PMID- 8521990
TI  - [The obtaining of isolated epithelial cells from the small intestine of cattle].

PMID- 8521991
TI  - [The estimation of free-radical lipid oxidation in the erythrocytes and blood
      plasma].
AB  - Modification of the spectrophotometric method for simultaneous determination of
      the concentration of primary, secondary and final products of the free-radical
      oxidation of lipids in the plasma and erythrocytes of the blood. The method
      permits estimating intensity of processes of free-radical oxidation as well as
      correlation between concentration of the indices in the plasma and in the
      erythrocytes. Changes in the correlations of dienic, trienic and oxodienic
      conjugates permit determining direction of metabolism of unsaturated lipids,
      degree of oxidation of fatty acids and peroxidation index.

PMID- 8521992
TI  - [The information value of the left ventricular end-systolic volume-pressure ratio
      for the noninvasive assessment of human cardiac contractile function].
AB  - To create a noninvasive method of myocardial contractility assessment and to
      evaluate its diagnostical significance, 84 patients with ischemic cardiac disease
      and 17 healthy persons were clinically investigated including real-time
      ultrasound sectoral scanning, bicycle ergometry, selective coronaroarteriography
      and blood pressure measurement. Using noninvasive approximations of end-systolic
      and maximal isovolumic pressures and left ventricular volume values at the end of
      systole and diastole, we constructed end-systolic pressure-volume relations
      (ESPVR) which were compared with relations obtained by traditional methods.
      Results of this work show that a slope of ESPVR obtained from the study of data
      of one cardiac cycle is a reliable contractility index more sensitive to small
      alterations in the contractile state of the heart than traditionally used
      ejection fraction and circumferential fiber shortening velocity. We suggest that
      the ESPVR obtained in such a manner has some advantages because it takes into
      account influences of the afterload changes reflex consequences. The results also
      support application of this method to early diagnosis of ischemic cardiac
      disease.

PMID- 8521993
TI  - [The morphofunctional characteristics of the thrombocytes in patients with
      refractory tachyarrhythmias].
AB  - Morphological and cytochemical features of peripheral blood thrombocytes from
      patients with paroxysmal tachyarrhythmias refractory to treatment with
      antiarrhythmic drugs were studied using modern techniques of fluorescence and
      electron microscopy. Blood samples of 33 patients were analyzed, 21 of them being
      refractory to treatment. Blood samples of 5 healthy persons served as controls.
      Nonactivated, activated, degranulated thrombocytes and their aggregates were
      counted in blood smears. Concentration of noncompensated negative charges in
      glycocalyx and activity of adenylate cyclase, phosphodiesterase of cyclic
      nucleotides and monoamine oxidase were determined by ultrastructural
      histochemistry techniques and mean content of alpha-granules was determined
      morphometrically. The morphofunctional state of thrombocytes in patients with
      refractory tachyarrhythmias was found to change significantly resulting in an
      increase in the number of irreversibly activated and degranulated forms and
      glycocalyx modification. These changes are supposed to represent an important
      component of the pathogenesis of resistance to drug treatment. The level of
      patients' sensitivity to the drug therapy correlates with the parameters under
      study indicative of changes in the thrombocyte surface and ultrastructure and of
      the number of free-circulating thrombocyte complexes. Under these conditions the
      deposition function of thrombocytes in restricted. The reactivity of platelets is
      also changed due to appearance of amorphous deposits on their surfaces which
      either protect or block the receptors of the cells.

PMID- 8521994
TI  - [The experimental modelling of a vertebrocardiac syndrome].
AB  - Ultrastructural investigations of the myocardium were carried out on 42 mature
      rabbits after formation of the fixed rotational thoracic vertebra subluxation by
      surgery. The dynamics of ultrastructural changes in the myocardium was determined
      15, 30, 45, 60, 90 and 180 days after the surgery procedure. Simultaneously
      changes in the spinal motional segment of animals were identified with
      accompanying mechanical influence on the nervous and vascular structures inside
      the intervertebral canal. Neural mechanisms of the cardiac function regulation
      may be disturbed. Changes in the myocardium are caused by: compression of neural
      structures inside the intervertebral canal; activation of receptors deformed in
      the stretched soft tissues of the spinal motional segment when vertebra
      subluxation is present.

PMID- 8521995
TI  - [Morphofunctional changes in the lysosomal apparatus of the peripheral blood
      neutrophilic leukocytes in aseptic inflammation].
AB  - The investigation was carried out on 47 adult rabbits. The reaction of lysosomal
      apparatus of neutrophilic leucocytes of peripheral blood was investigated under
      conditions of aseptic inflammation, caused by intramuscular injection of
      formaline. The conclusion is made that neutrophilic leucocytosis and a decrease
      of lysosomes in neutrophils under conditions of inflammation are nonspecific
      components of a general adaptation syndrome and result from the vivid
      granulocytopoesis and leucergy process.

PMID- 8521996
TI  - [The physiological basis of the compensatory-adaptive significance of expiratory
      bronchospasm].
AB  - A purposeful analysis of home and foreign literature has been made, its results
      being inconsistent with generally accepted notion of a bronchial spasm as a
      pathogenetic sign and so impossible to be logically interpreted. The analysis
      supports the supposition on the possibility of the manifestation of the
      expiratory bronchial spasm as a compensatory-adaptative mechanism directed to
      increase the intrathoracic pressure, alveolar-capillary diffusion of oxygen and
      oxygenation of the aerated blood in the case of hypoxemia. Results of examination
      of 30 miners with the expiratory bronchial permeability in the presence of the
      hypoxic and load-induced hypoxemia give grounds to confirm existence of the
      breathing regulation mechanism and to elaborate a differential approach for
      estimation of the bronchial spasm in patients with pulmonological diseases.

PMID- 8521997
TI  - [The effect of intermittent hypoxic training on pancreatic endocrine function in
      animals with diabetes mellitus].
AB  - The state of the pancreatic endocrine apparatus in diabetes, adaptation to
      hypoxia and both of them were studied in experiments with rats. Early stages of
      diabetes were accompanied by marked reconstruction of the pancreas. A decrease in
      the insulin level was followed by compensatory activation of glucagon- and
      somatostatine-producing systems which depended on the sex of animals. It was
      observed that adaptation to intermittent hypoxia exerted a positive effect on the
      diabetic process in rats, which was manifested by an increase in the insulin
      level in blood and beta-cells, inhibition of islet destruction, new formation of
      beta-cells in acinar tissue, and decrease of glucagon and somatostatine
      production.

PMID- 8521998
TI  - [The interrelationships of hypothalamic structures and the endocrine portion of
      the pancreas in diabetic C57BL/Ksj mice].
AB  - Interrelation between the hypothalamic nuclei and pancreatic endocrine fraction
      has been studied in mice of C57BL/KsJ line which were hetero- and homozygotic by
      diabetic gene db. The immunocytochemical method was used to determine content of
      insulin, glucagon and somatostatine in the Langerhans islet cells and
      morphohistochemical methods were used to estimate the state of hypothalamic
      structures. It has been shown that regulation of the pancreatic endocrine
      function and metabolic processes in which it participates by the hypothalamus may
      be provided at least by two mechanisms: neurohormonal one, connected with hormone
      secretion from paraventricular and supraoptic nuclei, and neuroconductory
      mechanism, connected with the ventromedial nucleus and lateral hypothalamic
      region.

PMID- 8521999
TI  - [In vitro comparison of instruments for root canal preparation. III. Study of the
      instruments from the viewpoint of shaping asymmetry].
AB  - The shape of the prepared root canals is not consistent with the original
      anatomical shape in the majority of curved canals. The discrepancy is dependent
      of the type of instrument, the original anatomical form of the root canal and the
      location of the measurement. The original shape of the root canal has to be taken
      into consideration in the selection of preparatory instruments because their
      application is limited by the above mentioned factor. The sonic and ultrasonic
      preparatory instruments form an exception in this respect due to their non
      aggressive way of shaping. These instruments cannot be disregarded in the
      preparation of curved root canals.

PMID- 8522000
TI  - [Effectiveness of intra-arterial chemotherapy in the management of intra-oral
      cancers and their lymphatic metastases].
AB  - The effect of complex therapy (intra-arterial chemotherapy and radical surgery)
      on primary tumours and their metastases was studied in 38 oral squamous cell
      cancer cases. The therapy had different effect on the primary tumours and their
      lymph node metastases. There was a close correlation between the number of
      metastatic lymph nodes and survival. The extension and the chemotherapeutic
      regression rate of metastatic lesions showed a significant correlation with
      patients' survival.

PMID- 8522001
TI  - [Surgical-orthodontic correction of unerupted upper canine teeth and motivation
      for the procedure from the patient's viewpoint].
AB  - The surgical correction of the retention of upper canines is made easier by the
      direct bonding method, furthermore it increases the chances of successful
      treatment. At the same time at teen-age the treatment is usually missing, since
      the persistent milk-teeth in the place of impacted canines are ensuring the
      aesthetic effect. The late treatment is motivated by aesthetic aspects also by
      loosing the milk-canines. Thus the indication of the treatment is a cure only
      from the orthodontist's aspect, from the patient's view it's only the aesthetics.

PMID- 8522002
TI  - [Major trends in the activities of the Oral Surgery Department at the Hungarian
      Central Military Hospital].
AB  - The author summarizes the main trends of activities of the Department of Oral
      Surgery of the 45-year old Central Military Hospital. Through the restructuring
      of the department the basis of the up-to-date therapeutic, educational and
      scientific activities corresponding to the tasks of a university teaching
      hospital has been created. The department takes part in the undergraduate and
      postgraduate education. Research programs have been elaborated primarily in the
      field of laser medicine, traumatology and reconstructive surgery. In the therapy
      both the dentoalveolar and maxillofacial surgery play a key role, in addition to
      the highly important military and disaster medicine.

PMID- 8522004
TI  - [Scanning electron microscopy of the resorption surface of deciduous teeth].
AB  - Based on a study of ten deciduous human teeth, (front teeth and molars) under a
      Scanning Electron Microscope type Tesla BS 300 we could observe that the
      differences of the mineralization levels are more striking in the peritubular
      dentin, then in the intertubular structures. The structural transformation
      increases by approaching the resorption surface. Near the enamel the resorption
      surface shows a two-edged demineralization. The mineralized part near the enamel
      is probably the result of the protecting processes of the human organism.

PMID- 8522003
TI  - [Hypnosis in dentistry. I. Comparative evaluation of 45 cases of hypnosis].
AB  - The use of meditative state for hypnotic induction in the dental practice was
      investigated in 45 cases. In 38 cases (84.4%) the hypnosis was found as a useful
      additional method. It was especially useful to reduce anxiety, and in some
      psychosomatic diseases.

PMID- 8522005
TI  - [Caries intensity and oral hygiene in adult dental patients in Budapest].
AB  - Authors examined 868, 15-69 age old, non-selected patients. DMF-T scores were
      between 7.8 and 24.69, DMF-S scores were between 14.78 and 67.39. Both data
      increased according to the age of the patients. The scores of the Periodontal
      Index (PI) were between 0.47 and 1.32, and the scores of the OHI-S between 1.10
      and 1.59. Among those patients, who were non-smokers, and regularly visited their
      dentist, better dental status and oral hygiene could be observed.

PMID- 8522006
TI  - [Comparison of the planimetric and gravimetric methods in the study of the
      efficiency of endodontic instruments].
AB  - Both gravimetry (measurement of weight loss of roots after root canal
      preparation) and planimetry (measurement of surface area corresponding to the
      removed dentin layer of canal walls on oro-vestibular and mesio-distal X-ray
      views of roots before and after the preparation) were used on the same samples
      for determination of the efficacy of root canal shaping instruments. There were
      no statistically significant differences between the results obtained using
      either the gravimetry or the planimetry indicating the evidence of reliability of
      results obtained using only the planimetry as a single method.

PMID- 8522007
TI  - [Scanning electron microscopy in the study of surface treatment methods used in
      the repair of porcelain-fused-to-metal restorations].
AB  - According to the literature the ceramic crowns are damaged in 1%-9% of the cases.
      In order to repair the damage with polimers, first the exposed surfaces have to
      be made microretentive. Our aim was to investigate with scanning
      electronmicroscope how the different surface treatment methods modify the
      structure of metal and ceramic surfaces. We applied two different methods of
      grinding: 40 microns grained diamond, K1 burs stone (SILISTOR) for ceramic and
      metal surfaces. The third surface treatment was the application of HF acid for
      ceramic surface and the sandblasting for metal surface. To achieve microretention
      the latter mentioned methods increased the most the retentive surface.

PMID- 8522008
TI  - [Cariologic and periodontal screening of children aged 7, 12 and 14 years in the
      city of Debrecen. II. Periodontal status and need for treatment].
AB  - The aim of present survey was to gain epidemiological data on periodontal
      condition of 7, 12 and 14 yrs old (40 children in 7, 92 children in 12 and 84
      children in 14 yrs old groups) schoolchildren as assessed by the CPITN. The
      peridontal health of children proved to be very poor. Only 33.3% of 7 yrs old,
      20.9% of 12 yrs and 13.1% of 14 yrs old children showed healthy gingiva. Bleeding
      on probing was observed in 66.7% of 7 yrs old group, in 19.8% of 12 and in 16.7%
      of 14 yrs old groups. The calculus prevalence was 0.0% of 7 yrs old children,
      56.0% in 12 and 44.7% in 14 yrs old groups. Oral hygiene instruction was needed
      by 66.7% of 7, 79.1% of 12 and 86.9% of 14 yrs old children. Scaling was
      necessary in 11.1% of 7, 59.3% of 12 and 70.2% of 14 yrs old groups. Complex
      treatment was needed in none of the groups examined.

PMID- 8522009
TI  - [Excretion of cefonicid and ceftriaxone into the saliva].
AB  - The serum and saliva levels of cefonicid (Monocid) and ceftriaxon (Rocephin) were
      studied after iv. administration on mice. It was found that both of the
      antibiotics were secreted well into saliva and their therapeutic values remained
      for 4-5 hours.

PMID- 8522010
TI  - [The role of dalacin C in the management of odontogenic inflammations].
AB  - The penicillin-metronidazole combination is well tried antibiotic therapy for the
      treatment of inflammations of dental origin. However, because of the rising
      number of penicillin-resistant bacterium strains and penicillin allergies, other
      antibiotics too are being applied ever more frequently. The literature data and
      the authors' own experience indicate that clindamycin (Dalacin C) may be used
      effectively against mixed infections of the oral cavity. A detailed account of
      the patients and the methods will be reported in the following article.

PMID- 8522011
TI  - [Computer tomography in implantology].
AB  - During the planning of implantation the CT method helps in determining the
      location of the implant and aids in choosing the right implant. It provides the
      following measurable information about the jaw-bones: height and width; exact
      location of bone deficiencies; the orovestibular shape of the alveolar process;
      the course of the mandibular canal; the location of the mental foramen; the
      location and size of the canalis incisivus; the area of the nasal cavity and the
      maxillary sinus; the quality of the bones and the relationship between cortical
      and spongious bone. In comparison to the X-ray examinations possession of these
      informations increase significantly the safety of planning before surgery.

PMID- 8522012
TI  - [What to do? Modern methods of patient information in the practice of oral
      surgery].

PMID- 8522013
TI  - [Prosthetic status, conditions of the oral mucosa and temporomandibular joint, as
      well as treatment needs in the elderly population of a Hungarian city (Gyor) II].
AB  - In a Hungarian city a special oral health survey concerning prosthetic status,
      oral mucosa and temporo-mandibular joint condition of the elderly population has
      been performed by standardized methods. The most frequent prosthetic finding was
      the removable prosthetic appliance (denture). It is suggested, that the number of
      dentures should be decreased with higher priority for the preservation of natural
      dentition and it should be achieved to change the dentures at proper intervals
      among denture-wearing patients. The prevalence of temporo-mandibular joint
      function-disturbances was low. In order to diagnose earlier the praecancerous
      lesions and conditions a regular oral health survey at least once a year among
      the people above 55 years of age should be organized.

PMID- 8522014
TI  - [The importance of professional cooperation in the management of orbital
      injuries].
AB  - The injuries of the maxilla and the mandible are usually composite, often
      requiring the close cooperation of professionals of various specialties. In the
      Central Military Hospital the authors have set up a team for the complex
      diagnostic and therapeutic management of patients with orbit injuries. The
      organizational aspects and basic principles of the team work are dealt with.

PMID- 8522015
TI  - [In vitro comparison of instruments for root canal preparation. I. Pilot study of
      the homogeneity of study groups].
AB  - If extracted human teeth are used for comparative study of root canal preparatory
      instruments the selection of roots into homogeneous test groups is decisive step
      of the experiment. On the basis our pilot USDA it is necessary not only to
      consider the Schneider angle and the length of root canal curvature but the
      surface area of root canals on the mesio-distal and oro-vestibular radiographs
      showing the projected view of the canals.

PMID- 8522016
TI  - [Excretion of erythromycin, clindamycin and lincomycin into the saliva].
AB  - In rabbit experiments (n = 10) the salivary and serum levels of several
      antibiotics were studied after per os (clindamycin, erythromycin and lincomycin)
      and iv. (erythromycin) administration. Erythromycin was excreted into the saliva
      in a considerable degree (in 60-75% of the serum level) and displayed
      therapeutical levels for 5-6 hrs, whereas clindamycin and lincomycin reached in
      the saliva only 25-30% of the serum level and therapeutic levels were maintained
      only for 3 hours.

PMID- 8522017
TI  - [Comparative evaluation of root canal shaping instruments tested on extracted
      human teeth. I. Comparison of traditional manual instruments and the Kerr-flex
      filing device].

PMID- 8522018
TI  - [Management of patients with maxillofacial injuries at the Oral Surgery
      Department of the Hungarian Central Military Hospital (analysis of a 10-year
      patient material)].
AB  - The authors have worked up the most important data of as many as 500 patients
      with malar and mandibular bone injuries. It is established that these injuries
      mostly derive from aggressive actions and traffic accidents. During this decade
      the ratio of injuries regarding the mandible and centre of the face has changed
      from 2.5:1 to 1:1. Since January 1, 1994 the number of managed injured patients
      has significantly increased, as a consequence of the maxillofacial service
      connected into the duty management in Budapest.

PMID- 8522019
TI  - [Hypnosis in dentistry 2. Amnesia, analgesia, loss of time perception:
      spontaneous manifestations during use of hypnosis in dentistry].
AB  - The frequency of occurrence of spontaneous amnesia analgesia and time distortion
      was investigated in 42 cases during dental treatment carried out under hypnosis.
      Amnesia occurred in 53.5% analgesia in 57.8% and time distortion in 64.0%.

PMID- 8522020
TI  - [Bonding strength and fracture resistance of artificial teeth in dental
      prostheses].
AB  - Debonding of plastic teeth from its denture base has been frequently experienced
      in our prosthetic practice. Three of nine products investigated have fulfilled
      the requirements for bonding according to ISO test 3336. Loading forces necessary
      to produce fractures varied between 170-810 N within the tooth and 80-230 N at
      the tooth-denture base interface. Comparative significances were noted for the
      mean breaking force against fracture and debonding when comparing the resistance
      of "Acry Rock" to the other eight materials tested. Maximizing the extension of
      the polymerization surface through a larger surface area of individual teeth
      seemed to be a significant factor in the determination of the debonding force
      necessary to produce fracturing.

PMID- 8522021
TI  - [In vitro comparison of instruments used for root canal preparation. II.
      Effectiveness of the instruments].
AB  - According to our examination, the anatomical shape of the root canal can
      influence the function of the examined instrument, therefore it's advisable to
      pay attention to the canal's curve at the selection of the root canal cutting
      instrument. Concerning the examined instruments, the least effective was the
      ultrasonic instrument.

PMID- 8522022
TI  - [Effect of preventive fluoride treatment in childhood on dental conditions in
      adults].
AB  - The purpose of the study was to compare the dental health status of three groups
      of adults aged 18-47. In the first group belonged the population, that consumed
      in their childhood salt containing 250-350 mg fluoride per kg. The second group
      consisted of those who drank water with an optimal fluoride concentration (1
      mg/kg). The individuals without fluoride prevention formed the third group. The
      results showed, that the consumption of fluoridated drinking water or salt in
      childhood has a life-long beneficial effect on the dental health of the adult
      population.

PMID- 8522023
TI  - [Metal-based esthetic inlays].
AB  - The aesthetic appearance and marginal accuracy of porcelain fused to metal
      inlays/onlays have been evaluated in this study. The metal frameworks of the
      restorations were fabricated by casting or by galvanic techniques. Both the gold
      collar and the insufficient thickness of covering porcelain influenced the
      aesthetic features of inlays negatively. The good aesthetic appearance achieved
      in case of onlays was independent of manufacturing procedures. Inlays/onlays
      accomplished by galvanic technique showed a better marginal fitting as compared
      to that of cast ones.

PMID- 8522024
TI  - [Tooth extraction in patients undergoing anticoagulant therapy].
AB  - The authors describe the possibilities of tooth extraction in patients who
      receive anticoagulant therapy. They propose the hospitalization of these
      patients. The authors also account of good results wits utilizing Lyostipt and
      Dicynone.

PMID- 8522025
TI  - [Excretion of fluoroquinolones into saliva].
AB  - The excretion of three fluoroquinolones derivatives into the saliva were studied
      in animal experiments. Ofloxacin per os administered to rabbits was excreted into
      the saliva well, and maintained the therapeutic level long--about 7 hours.
      Pefloxacin and ciprofloxacin iv. administered to mice were similarly excreted
      into the saliva at therapeutic levels and retained the antibacterial level for
      about 4 hours.

PMID- 8522026
TI  - [Use of hydroxy-propyl-methyl cellulose (methocel) and carboxy-methyl cellulose
      containing artificial saliva in the symptomatic treatment of xerostomia].
AB  - Salivary gland hypofunction is a common sequela of Sjogren's syndrome and
      irradiation treatment of tumors in head and neck region. The aim of the present
      study was to evaluate the therapeutic effect of a recently developed hydroxy
      propyl-methyl-cellulose (HPMC) containing artificial saliva and to compare it
      with that of the carboxy-methyl-cellulose (CMC) based saliva substitute. The
      therapeutic effects of both preparations were assessed by means of self
      administered questionnaires which had to be completed before and after the use of
      each type of artificial saliva after one week treatment. We found significant
      improvement in symptoms of nocturnal discomfort and difficulty in speech, and
      results were better in case of HPMC based artificial saliva. The retention time
      in oral cavity and the frequency of daily administration also were better in case
      of HPMC containing preparation. It is concluded that the use of HPMC containing
      artificial saliva can be recommended in the treatment of salivary hypofunction.

PMID- 8522027
TI  - Analysis of beta-agonists in urine and tissues by capillary gas chromatography
      mass spectrometry: in vivo study of salbutamol disposition in calves.
AB  - The fate of salbutamol sulphate given orally has been investigated in calves. The
      urinary excretion rate and the tissue distribution of this beta-agonistic drug
      were studied by capillary gas chromatography coupled to low resolution mass
      spectrometry (GC-LRMS) under electron impact (EI) ionization mode, using an
      hexadeuterated salbutamol analogue as the internal standard. The parent drug and
      metabolites were extracted via solid phase extraction (SPE) mixed-phase
      containing disposable columns and analysed as their trimethylsilyl derivatives. A
      more efficient clean-up had to be carried out for tissue samples. An acidic
      precipitation followed by a liquid-liquid extraction were therefore performed
      before the SPE. Moreover, the problem of tissue digestion was elucidated by means
      of an ultrasonic probe. Samples were also analysed before and after enzymic
      hydrolysis using purified beta-glucuronidase and a mixture of beta-glucuronidase
      and arylsulphatase, to obtain evidence of phase II conjugation mechanisms. Both
      free salbutamol and conjugated metabolites were detected in urine and tissue
      samples. Except for liver or kidney, salbutamol was rapidly cleared from most
      tissues after a withdrawal period. The possible excretion of some phase I
      metabolites was also investigated, using further analyses under positive chemical
      ionization LRMS and high resolution mass spectrometry (HRMS).

PMID- 8522028
TI  - Evaluation of censored contamination data.
AB  - Laboratory measures of low-level contamination are typically strongly skewed, and
      observations below a specified detection limit are recorded merely as not
      detectable or less than a specified limit. In these circumstances, a full
      description of the distribution requires assumptions about the form of the lower
      tail. If such assumptions are made, the distribution can be described in terms of
      the usual parameter estimates. The assumptions can be checked if similar samples
      can be accurately assessed using specialized equipment with a very low detection
      limit. Methods of fitting suitable distribution to data of this sort are
      discussed, and evaluated using results from a laboratory with equipment capable
      of measuring very low contamination levels. Estimates based on the complete data
      are compared with estimates based on assumed detection limits.

PMID- 8522029
TI  - A survey on veterinary drug use and residues in milk in Hyderabad.
AB  - A survey on veterinary drug use and residues in milk was carried out in Hyderabad
      (India) and surrounding suburban villages. Mastitis was the most common disease
      reported; oxytocin and oxytetracycline were frequently used in veterinary
      formulations. Of 205 milk samples analysed, 9% of market samples and 73% of
      individual animal milk samples contained oxytetracycline residues. None of the
      government dairy samples contained oxytetracycline residues. Maximum
      oxytetracycline consumption through milk was calculated to be 0.045 mg/kg bw/day.
      The levels ranged from 0.2 to 1.4 micrograms/ml in market milk samples and from
      0.2 to 6.7 micrograms/ml in samples obtained from individual buffaloes. It was
      found that the oxytetracycline residues affect curd setting, the extent depending
      on the amount of residue.

PMID- 8522030
TI  - Element residues in food contact plastics and their migration into food
      simulants, measured by inductively-coupled plasma-mass spectrometry.
AB  - Polymers intended for food contact use have been analysed for inorganic residues
      which can be attributed to a range of substances employed as polymerization aids
      (e.g. catalysts), or to additives incorporated into the polymer to fulfil a
      specific task (e.g. lubricants). The migration of these residues into food
      simulants was studied. Residues were determined by using the multi-element
      capability of Inductively-Coupled Plasma-Mass Spectrometry (ICP-MS). Semi
      quantitative analysis was carried out on acid digests of polymer materials,
      obtained by microwave heating in sealed Teflon containers. Limits of detection in
      the polymer were generally less than 1 mg/kg. Migration experiments were carried
      out with three food simulants and under two sets of conditions. Analysis for
      element residues was performed directly or, in the case of olive oil, on an
      emulsion of the simulant. Migration of certain elements into aqueous simulants
      was observed: Zr from polystyrene (650 micrograms/kg), Sb from polyethylene
      terephthalate (4 micrograms/kg) and Mg from acrylonitrile/butadiene/styrene
      copolymer (50 micrograms/kg). In all cases, where limits of detection permit, the
      levels which migrated from polymer to stimulant were less than proposed limits on
      migration.

PMID- 8522031
TI  - Determination of migrants in and migration from nylon food packaging.
AB  - A method was developed to determine the amount of residual oligomers in nylon
      food packaging. In addition, a method was developed to measure oligomers that
      migrate to a food-stimulating liquid (oil) during oven cooking conditions. It was
      found that the total amount of nylon 6/66 oligomers that migrated from an oven
      baking bag to oil after heating for 30 min at 176 degrees C was 15.5 micrograms/g
      (ppm) or 11.9 micrograms/cm2, which represented 43% of the total amount of
      oligomers present in the packaging material.

PMID- 8522032
TI  - Incidence and abundance of mycotoxins in maize in Rio Grande do Sul, Brazil.
AB  - The levels of aflatoxins B1, B2, G1, and G2, ochratoxin A, zearalenone and
      sterigmatocystin were determined by thin-layer chromatography in 36 samples of
      stored maize in the state of Rio Grande do Sul; the samples were obtained from
      May to September 1988, 23 samples were from silos and 13 samples were collected
      directly from farms. In 34.8% of the samples from silos aflatoxin B1+G1 was
      detected in concentrations that varied from 12 to 906 micrograms/kg. In 13% of
      the samples from silos aflatoxin B2 was detected in concentrations that varied
      from 48 to 180 micrograms/kg. In 9% of the samples from silos aflatoxin G2 was
      detected in concentrations that varied from 6 to 11 micrograms/kg. In 23% of the
      samples collected directly from farms aflatoxin B1+G1 was detected in
      concentrations that varied from 10 to 14 micrograms/kg. Ochratoxin A, zearalenone
      and sterigmatocystin were not detected at any time.

PMID- 8522033
TI  - Mycotoxins and fungi in wheat stored in elevators in the state of Rio Grande do
      Sul, Brazil.
AB  - Samples of wheat harvested from 1988 to 1990 and stored in elevators in the south
      of Brazil (12 Brazilian, 4 Argentinian and 2 Uruguayan) were analysed in 1990 for
      14 mycotoxins: deoxynivalenol (DON), nivalenol, diacetoxyscirpenol (DAS), T-2 and
      HT-2 toxins, T-2 triol, T-2 tetraol, aflatoxins B1, B2, G1, G2, ochratoxin A
      (OCHRA A), zearalenone and sterigmatocystin. One sample (1988 harvest) was
      contaminated with OCHRA A (0.04 microgram/g) and three other samples (1990
      harvest) were contaminated with DON (0.40 microgram/g), DAS (0.30 microgram/g), T
      2 (two samples, 0.35 and 0.36 gamma g/g) and T-2 tetraol (1.68 micrograms/g).
      Fusarium graminearum Schwabe was found in the 1990 samples with a relative
      incidence ranging from 1 to 22% and predominated in Argentinian and Uruguayan
      wheat (1990 harvest). Fusarium dimerum Penzig (8-75%) was the main Fusarium sp.
      in Brazilian wheat from the 1990 harvest.

PMID- 8522034
TI  - Natural occurrence of acetylated derivatives of deoxynivalenol and nivalenol in
      wheat and barley in Japan.
AB  - Thirty-four samples of domestic wheat and barley grains, collected from eight
      prefectures of different locations in Japan and previously determined to be
      positive for deoxynivalenol (DON), nivalenol (NIV) and/or zearalenone (ZEA), were
      analysed for acetylated derivatives of DON and NIV by gas chromatography-mass
      spectrometry. In addition to DON and NIV, 3-acetyldeoxynivalenol (3-ADON), 15
      acetyldeoxynivalenol (15-ADON) and 4-acetylnivalenol (4-ANIV) were found in 25, 4
      and 14 samples, respectively. A regional difference in the DON and NIV
      contamination of Japanese wheat and barley was suggested: DON was the major
      trichothecene in the northern district and NIV in the central districts, whereas
      in the southern districts the DON level was similar to or slightly higher than
      the NIV level. 3-ADON occurred together with DON in almost all prefectures
      examined, whereas 15-ADON was found only in samples from northern districts. In
      addition, a high correlation (r = 0.974, n = 23) between levels of DON and its
      acetates (3-ADON and 15-ADON) was noted. These results may also suggest the
      possibility of a geographic difference in the distribution of different
      chemotypes of Fusarium species producing these trichothecenes in Japan.

PMID- 8522035
TI  - Role of rice and cereal products in dietary cadmium and lead intake among
      different socio-economic groups in south India.
AB  - A study was conducted to evaluate the concentration of cadmium and lead in rice
      and cereal products commonly consumed in South India. Samples from retail outlets
      were purchased and analysed for cadmium and lead using graphite tube atomic
      absorption spectrophotometry. The results indicated varying concentrations of
      these metals in different rice and cereal products. The daily dietary intake of
      cadmium and lead varied among different socio-economic groups, based on
      occupation, and choice of consumption. The findings suggest that rice is the
      major source of cadmium and lead among the rural population and economically
      deprived class. The source of intake of toxic metals appears to be more diverse
      in the case of the urban middle class and the economically privileged class of
      South India.

PMID- 8522036
TI  - Polycyclic aromatic hydrocarbon contamination in the Italian diet.
AB  - The content of total and carcinogenic polycyclic aromatic hydrocarbons (PAHs) in
      Italian foods was measured. The highest levels of PAHs were found in pizza baked
      in wood-burning ovens and barbecued beef and pork. Relatively high levels were
      also found in beet greens and squash, apples and bread, fried beef, pork and
      rabbit, cured meats and chocolate. Conversely low levels were detected in
      potatoes and cooked fish, beverages and eggs. The daily intake of total and
      carcinogenic PAHs also was calculated by multiplying the average consumption of
      each food by its mean concentration of PAHs. Cereal and milk products, meat,
      vegetables and fruits were the highest contributors to total PAH intake, since
      these products are the most important dietary components in Italy. The calculated
      total dietary PAH intake was 3 micrograms/day per person. The calculated intake
      of carcinogenic PAHs was 1.4 microgram/day per person. The dietary intake of PAHs
      was high compared with the calculated respiratory intake (370 ng/day) owing to
      polluted city air in Italy. These results confirm that food is the major source
      of human exposure to PAHs, due in particular to the high consumption of
      contaminated cereal products.

PMID- 8522037
TI  - Quantitative structure-activity relationships and COMPACT analysis of a series of
      food mutagens.
AB  - Quantitative structure-activity relationships between chemical structure and Ames
      mutagenicity for a group of 24 food mutagens, including 17 cooked-food
      heterocyclic amines, have been determined. For the TA98 strain of Salmonella
      typhimurium (frameshift mutagens) the best correlation of mutagenicity is with
      molecular diameter (R = 0.91), while for the TA100 strain (base-pair mutations)
      the best correlation is with delta E, the energy difference between the lowest
      unoccupied and highest occupied molecular orbitals. High mutagenicity is related
      to high values of molecular diameter, hence to planarity and to high values of
      the COMPACT ratio ([area/depth2]/delta E). High mutagenicity is also related to
      low values of delta E. Consequently, highly mutagenic and potentially
      carcinogenic food chemicals can readily be identified as substrates of cytochrome
      P4501 (CYP1) and may therefore be detected by the COMPACT procedure. Highly
      mutagenic compounds also exhibit high values of dipole moment.

PMID- 8522038
TI  - The preschool "passage". An overview of dental health.
AB  - Children undergo major transformations between birth and approximately 5 years of
      age. The most common examples are personality development and the potential
      explosiveness of the course of the disease caries. Each demands recognition,
      assessment of degree of difficulty, and an adaptation by the dentist. Starting
      dental care for children early is based on the anticipated time children can
      develop disease, the fact that most dental disease is preventable, and the desire
      to gain the trust of the child by first, minimizing the need for invasive
      procedures. Dental trends set in the preschool period tend to carry for many
      years. The dentist's assessment of the degree of difficulty is the first key in
      successful care for each child. The general dentist and pediatric dentist both
      play important and complementary roles in the care of children. There are
      differences in the practice habits between the two. Self assessment of skills for
      common situations leads to improved care. Because children don't vote, a
      responsibility falls on the health care provider to advocate for children in the
      political and professional arenas.

PMID- 8522039
TI  - Dental caries risk assessment and prevention.
AB  - Although dental caries in preschool children has declined in the past 20 years,
      the decrease is not observed equally across all populations. Considerable benefit
      could be achieved if the children at high risk could be identified before lesions
      develop. The best predictors of dental caries in preschool children are previous
      caries history, especially nursing bottle caries, and the salivary mutans
      streptococci levels. Other caries risk factors include inadequate oral hygiene
      practices, deficient fluoride exposure, low socioeconomic status, and familial
      caries patterns. Children at high caries risk should be considered for more
      intensive home fluoride programs, such as brushing the child's teeth with a pea
      size amount of either 0.4% SnF2 or 1.1% NaF gels. Frequent professional fluoride
      treatments can be substituted if there is poor compliance with home programs.
      There is little documentation that dietary modification and plaque control and
      sealant programs are cost-effective measures for preventing caries in preschool
      children.

PMID- 8522040
TI  - Case planning and management according to caries risk assessment.
AB  - Ultimately, the dentist's role is to guide children through their growth and
      development free of disease. The dentist must recognize each child's unique
      susceptibility to caries and each parent's interest, competency, and
      accomplishment in controlling this disease. With this recognition, it is possible
      to tailor the frequency and content of dental visits necessary to maintain a
      child caries-free. Similarly, the frequency of examinations, office topical
      fluoride treatments, radiographs, and other diagnostic or preventive
      interventions depends upon the dentist's assessment of how intense professional
      efforts need to be to help parents maintain their children in health. Goldman and
      Burket summarized the relationship between science and practice and detailed the
      responsibilities of clinicians with the following words: "The practice of
      dentistry is an art in which the teachings of dental science are put to their
      practical application. A patient visits the dentist for consultation on the state
      of health of the dentition, with the expectation that everything possible will be
      done not only to repair or help heal by therapeutic correction any disease
      present but also to prevent disease from occurring, if possible." Treating caries
      at the level of the disease process to prevent its expression, progression, and
      ultimate dental destruction is the highest calling and deepest challenge facing
      dentists who care for young children. Techniques including risk assessment,
      triage, tailored care, and thoughtful treatment grounded in dental and behavioral
      science have put that goal within reach of dentists and parents to the great
      benefit of children.

PMID- 8522041
TI  - Restorative dentistry for preschool children.
AB  - Successful management of the behavior of the preschool child is a prerequisite
      for the dental experience to be pleasant for both the child and the dentist.
      There are many ways for the dentist to interface with children, but none is as
      desirable with cooperative or potentially cooperative preschool children than
      techniques in the linguistic domain. Fortunately, because most children are very
      competent in communicating in language sometime around their third birthday, such
      techniques are reliably effective with preschool children. Knowing the reasons
      why a seemingly potentially cooperative preschooler may not be so is important to
      the dentist seeking mastery skills in working with this age group. Another
      extremely important issue in behavioral pediatric dentistry at this time is the
      role of the parents in the dental appointment and their right to informed consent
      for certain behavioral management strategies.

PMID- 8522042
TI  - Personality development. Managing behavior of the cooperative preschool child.
AB  - Because communication is so important to the management of child behavior by the
      dentist, it must be remembered that the development of the child mentally,
      emotionally, socially, and cognitively is very important. The importance of the
      dentist's behavior management skills cannot be overemphasized as a determinant to
      the successful dental experience for the preschool child. This article provides
      an overview of behavior management domains for the preschool child, discusses the
      origin of misbehavior for seemingly "normal" children, and reviews the parental
      dimension of contemporary pediatric dentistry, and the dentist's role as an
      ontological coach.

PMID- 8522043
TI  - Managing behavior of precooperative children.
AB  - Disruptive behaviors, particularly from those lacking in cooperative ability,
      often are prompted by the need to protest an unpleasant situation and the impulse
      to protect oneself from perceived danger. Such behaviors, depending on the
      patient's age and cognitive ability, should be seen as an attempt of the child to
      cope with a frightening situation. The inherent challenge for both clinician and
      parent is to avoid unpleasant and unproductive confrontations from the outset and
      to create an environment to facilitate the child's ability to ultimately accept
      care, protect the child's self-esteem, foster a positive attitude toward care,
      and enhance the work quality and efficiency of the dental personnel. Use of
      behavioral management strategies that permit accomplishing these objectives have
      been described. The reader is encouraged to pursue further knowledge and
      expertise to make best use of nonaversive strategies for management of the
      precooperative child.

PMID- 8522044
TI  - Traumatic injuries in the preschool child.
AB  - The dental management of traumatic injuries in the preschool child demands a
      careful and methodical approach to the clinical patient care. Insurance claims
      and litigation possibilities require detailed documentation of the accident, the
      nature and extent of the injury and all treatment rendered, follow-up care, and
      verbal instructions given to the parent. The prognosis of the treatment and the
      damage to the permanent teeth depend upon the nature and extent of the injury
      and, in part, upon the treatment rendered and the follow-up care received by the
      patient. The dental records must be retained until the permanent teeth erupt to
      fully assess the extent of the damage to the developing dentition.

PMID- 8522045
TI  - Periodontal and soft-tissue abnormalities.
AB  - Young children come to our offices with a variety of periodontal and soft-tissue
      abnormalities, which require accurate diagnosis, treatment or reassurance, and
      possible referral to our medical colleagues. Periodic review of soft-tissue
      lesions can help the dental team to recognize both common and rare abnormalities
      affecting young children. Recent years have brought new insights into the
      etiology and treatment of periodontal diseases of children, making it possible to
      prevent or treat many formerly untreatable conditions.

PMID- 8522046
TI  - Habits affecting dental and maxillofacial growth and development.
AB  - In concluding this discussion, it is apparent that altered oral function or rest
      position may have a significant influence on the developing orofacial region. In
      the case of non-nutritive sucking habits, the child's commitment and desire to
      stop the habit is important to the successful elimination of the habit. At times,
      a hands-off approach is our best approach. Other habits are managed by addressing
      their cause. We, as dentists, have the ability to influence this process through
      the proper identification and management of these problems.

PMID- 8522047
TI  - Dental practice considerations.
AB  - Treating young children, working through an intermediary (the parenting adult),
      obtaining informed consent, and reporting suspected child abuse bring extra
      pressures to the dentist and staff members unless the protocol for each step is
      established and followed precisely. Managing for fiscal soundness and making a
      profit are other professional responsibilities. Counterbalancing the many
      pressures, the dentist who treats young children enjoys an added measure of
      pleasure beyond that experienced by many colleagues by helping a young child cope
      with the stresses of treatment, leading a child into a lifetime free of dental
      disease, and winning the trust and approval of parents or guardians. All of these
      aspects make dentistry a profession that provides a lifetime of excitement,
      fulfillment, learning, and constant opportunities for growth.

PMID- 8522048
TI  - Oral health policies and programs affecting the preschool child.
AB  - Although many policies and programs address the oral health of children, those
      specifically dealing with the preschool child are few. Review of existing policy
      suggests a lack of coherence or emphasis on the preschooler as a separate focus
      for oral health efforts. The importance of locating preschool children within
      existing policies and programs lies in insuring their access to care and to the
      benefits of educational and other preventive efforts directed to oral health. The
      experience of dentists advocating for children in California illustrates the
      value of an awareness of policies and programs directed at the preschool
      population. In 1990, a lawsuit brought forth by a coalition of dentists and other
      child advocates resulted in changes in the Denti-Cal (Medicaid) program for the
      benefit of children served. These changes increased both access and use by
      increasing fees and attracting more providers. Two years later, California
      attempted to stem the costs of success and tried to switch to a mandated
      capitated program for all Medicaid recipients. Again, through legal action, child
      advocates were able to argue successfully that such a move would have a negative
      impact on the children of California. The outcome of the legal action in this
      situation is still to be decided at this writing, but the series of events and
      the success of the advocate-dentists speak to the value of a working knowledge of
      the programs available for children. An individual dentist can also benefit
      individual children by knowing approved and covered procedures for their care,
      programmatic characteristics for situations requiring referral, and resources for
      educational materials. In many cases, knowledge of policies and programs is as
      valuable as the care dentists render.

PMID- 8522049
TI  - Preschool children. Need and use of dental services.
AB  - There have been major decreases in dental diseases, but many youngsters are still
      in need of care, especially low-income and medically compromised children.
      Additionally, family structure and economic changes are placing children at
      increased risk for dental diseases. Although there is a progressive increase in
      the use of services, many children don't have insurance coverage and do not
      receive preventive and restorative dental care. The preschool years are a
      foundation period for children, but many continue to receive an uncertain start.

PMID- 8522050
TI  - Delivery systems for preschool children.
AB  - The United States dental care delivery system generally performs well for those
      who gain access and can afford necessary care; however, many segments of the
      population with significant levels of dental disease find it difficult or
      impossible to avail themselves of the potential benefits that the system has to
      offer. Preschool children are no exception, and they often receive little or no
      consideration in epidemiologic studies or policy development. Increasing
      awareness and improving preschooler's access to needed services will require
      fundamental changes in attitudes, policies, and behaviors on the part of the
      public, public officials, and health care professionals, including those within
      the dental profession.

PMID- 8522051
TI  - Genetic analysis of NIDDM. The study of quantitative traits.
AB  - Many studies are in progress worldwide to elucidate the genetics of NIDDM.
      Nevertheless, few articles are available that combine the interdisciplinary
      fields of medicine, genetics, physiology, and statistics in order to provide the
      scientific rationale for such an endeavor. Here we describe the methodology and
      background necessary to study the genetics of NIDDM and discuss how to analyze
      the data. We also provide a detailed bibliography for researchers and a glossary
      for those who are not experts in the field. In particular, we wish to emphasize
      the analysis of intermediate quantitative traits as a means to dissect the
      genetic basis of NIDDM.

PMID- 8522052
TI  - Long-term results of early cyclosporin therapy in juvenile IDDM.
AB  - In juvenile IDDM patients, immunosuppression with cyclosporin A allows partial
      beta-cell function recovery and transient remissions of insulin dependency. The
      effects of this therapeutic approach, however, have not been evaluated in the
      long-term, since no reported trial exceeded 1 year. Here we analyze 130 diabetic
      children followed at our institution during the first years of their disease.
      Cyclosporin was given to 83 of them at an initial dose of 7.2 +/- 0.1 mg.kg-1.day
      1, which was decreased stepwise then interrupted after 6-62 months, depending on
      the response to therapy. A total of 47 diabetic children, who served as control
      subjects in two trials, were pooled for comparison. Over 4 years, the cyclosporin
      treated group kept plasma C-peptide approximately twice as high as the control
      group (P < 0.02). It took 5.8 +/- 0.6 years for C-peptide secretion stimulated by
      glucagon to become undetectable in the cyclosporin group versus 3.2 +/- 0.6 years
      in the control group (P < 0.02). Average insulin dose remained lower by 0.2-0.4
      U.kg-1.day-1 and glycated hemoglobin by approximately 1% in cyclosporin-treated
      patients (P < 0.02), who also had less hypoglycemia than the diabetic control
      subjects (P < 0.05). After 4 years, differences between the groups became
      nonsignificant. We observed no significant secondary effects of cyclosporin. In
      conclusion, positive effects of low-dose cyclosporin in recently diagnosed
      clinical IDDM patients are prolonged beyond interruption of the drug. The
      magnitude and duration of the benefit, however, do not appear sufficient to
      justify this immunosuppressive treatment in clinical practice.

PMID- 8522053
TI  - Impaired vasoconstriction to endothelin 1 in patients with NIDDM.
AB  - Microvascular disease is an important cause of morbidity in diabetes. There is
      evidence that impaired autoregulation of blood flow is involved in the
      pathogenesis of diabetic microangiopathy. The vascular endothelium plays a
      central role in the regulation of vascular tone. Endothelin (ET)-1 is a potent
      endothelium-derived vasoconstrictor substance that contributes to basal vascular
      tone. Impaired vasoconstriction in response to endogenous ET could result in
      hyperperfusion and subsequent microvascular damage. The purpose of our study was
      to determine whether vascular responses to locally administered ET-1 are impaired
      in NIDDM. Nine patients with NIDDM and 12 control subjects underwent cannulation
      of the nondominant brachial artery. Forearm blood flow (FBF) was measured at
      baseline and during the drug infusion using strain-gauge venous occlusion
      plethysmography. ET-1 (5 pmol/min) was infused for 60 min at a rate of 1 ml/min.
      FBF was measured during the first 5 min of the infusion and at 5-min intervals
      thereafter. Results were expressed as change in FBF from baseline (ml.100 ml
      1.min-1) and were analyzed using repeated measures analysis of variance and
      Dunnett's test of multiple comparisons. Control subjects showed a gradual onset
      of vasoconstriction in response to ET-1, which reached maximum at 35 min (1.1
      ml.100 ml-1.min-1; P < 0.01). There was no reduction in FBF in response to ET-1
      in the diabetic group. The differences between the diabetic and control groups
      were significant (P < 0.03). In conclusion, ET-1 infused locally at 5 pmol/min
      does not cause vasoconstriction in patients with NIDDM.

PMID- 8522054
TI  - Effects of insulin on vascular tone and sympathetic nervous system in NIDDM.
AB  - Chronic activation of the sympathetic nervous system may be a pathogenetic
      mechanism by which hyperinsulinemia induces cardiovascular damage in insulin
      resistant NIDDM patients. The influence of physiological hyperinsulinemia
      (approximately 700 pmol/l) on basal and stimulated sympathetic outflow was
      studied in 12 lean normotensive subjects with well-controlled NIDDM without
      complications and in 13 matched control subjects. Forearm blood flow (FBF) was
      measured with forearm plethysmography; sympathetic nervous system activity was
      assessed by the [3H]norepinephrine (NE) tracer method. NIDDM patients were
      insulin resistant (glucose infusion rates 31.8 +/- 3.8 vs. 48.7 +/- 2.0 mumol.kg
      1.min-1 in control subjects, P < 0.01). After a mixed meal, NIDDM patients showed
      a hyperinsulinemic response (2-h insulin levels: NIDDM patients 324 +/- 34
      pmol/l, control subjects 165 +/- 19 pmol/l, P < 0.001). Insulin infusion induced
      a vasodilator response (not significantly different between the groups). Arterial
      plasma NE levels and total-body NE spillover increased significantly (total
      spillover in NIDDM patients from 0.77 +/- 0.09 to 1.18 +/- 0.16 nmol.m-2.min-1,
      in control subjects from 0.98 +/- 0.14 to 1.23 +/- 0.18 nmol.m-2.min-1, P < 0.01
      for all, not different between groups). Total-body NE clearance did not change.
      Sympathetic stimulation (lower-body negative pressure [LBNP] 15 mmHg) induced
      forearm vasoconstriction and increased arterial and venous plasma NE and total NE
      spillover. Responses of FBF and NE kinetics to LBNP were not significantly
      different between groups and were not altered by hyperinsulinemia. Although these
      nonobese subjects with uncomplicated NIDDM showed postprandial hyperinsulinemia
      and resistance to the effect of insulin on glucose metabolism, this group was not
      resistant to the vasodilator and sympathetic stimulant effects of insulin.
      Responses to sympathetic stimuli (LBNP) were normal and unaffected by
      physiological hyperinsulinemia. Therefore, because of daily life
      hyperinsulinemia, chronic sympathetic stimulation could be operative in these
      patients and may explain the increased incidence of hypertension and/or
      cardiovascular complications.

PMID- 8522055
TI  - Improvement of insulin action in diabetic transgenic mice selectively
      overexpressing GLUT4 in skeletal muscle.
AB  - To investigate the role of glucose transporter expression in whole-body glucose
      homeostasis, we have created transgenic mice that have a 2.0- to 3.5-fold
      increase in GLUT4 glucose transporter level in skeletal muscle and heart. This
      increase is sufficient to significantly improve insulin action and to reduce
      basal blood glucose levels in transgenic streptozotocin-induced diabetic mice.
      These results provide the first evidence of a direct causality between skeletal
      muscle GLUT4 transporter level and overall insulin responsiveness.

PMID- 8522056
TI  - Enhanced insulin action due to targeted GLUT4 overexpression exclusively in
      muscle.
AB  - Dysregulation of GLUT4, the insulin-responsive glucose transporter, is associated
      with insulin resistance in skeletal muscle. Although skeletal muscle is the major
      target of insulin action, muscle GLUT4 has not been linked causally to whole-body
      insulin sensitivity and regulation of glucose homeostasis. To address this, we
      generated a line of transgenic mice that overexpresses GLUT4 in skeletal muscle.
      We demonstrate that restricted overexpression of GLUT4 in fast-twitch skeletal
      muscles of myosin light chain (MLC)-GLUT4 transgenic mice induces a 2.5-fold
      increase in insulin-stimulated 2-deoxyglucose uptake in transgene-overexpressing
      cells. Consequently, glycogen content is increased in the fast-twitch skeletal
      muscles under insulin action (5.75 +/- 1.02 vs. 3.24 +/- 0.26 mg/g). This
      indicates that insulin-stimulated glucose transport is partly rate-limiting for
      glycogen synthesis. At the whole-body level, insulin-stimulated glucose turnover
      is increased 2.5-fold in unconscious MLC-GLUT4 mice. Plasma glucose and insulin
      levels in MLC-GLUT4 mice are altered as a result of increased insulin action. In
      2- to 3-month-old MLC-GLUT4 mice, fasting insulin levels are decreased (0.43 +/-
      0.05 vs. 0.74 +/- 0.10 microgram/l), whereas normal fasting glycemia is
      maintained. Conversely, 7- to 9-month-old MLC-GLUT4 mice exhibit decreased
      fasting glycemia (5.75 +/- 0.73 vs. 8.11 +/- 0.57 mmol/l) with normal insulin
      levels. Fasting plasma lactate levels are elevated in both age groups (50-100%).
      Additionally lipid metabolism is affected by skeletal muscle GLUT4
      overexpression. This is indicated by changes in plasma free fatty acid and beta
      hydroxybutyrate levels. These studies underscore the importance of GLUT4 in the
      regulation of glucose homeostasis and its interaction with lipid metabolism.

PMID- 8522057
TI  - Glucose-regulated translational control of proinsulin biosynthesis with that of
      the proinsulin endopeptidases PC2 and PC3 in the insulin-producing MIN6 cell
      line.
AB  - In the short term (< 2 h), proinsulin biosynthesis is predominately glucose
      regulated at the translational level; however, the details at the molecular level
      behind this mechanism are not well defined. One of the major hindrances for
      gaining a better understanding of the proinsulin biosynthetic mechanism has been
      a lack of an abundant source of beta-cells that express a phenotype of regulated
      proinsulin biosynthesis in the appropriate 2.8-16.7 mmol/l glucose range as
      defined in normal pancreatic islets. In this study, we demonstrate that in the
      MIN6 cell line, specific glucose-regulated translational control of proinsulin
      biosynthesis is present in the appropriate glucose concentration range. In
      addition to that of proinsulin, the biosynthesis of the two proinsulin conversion
      endopeptidases, PC2 and PC3, was coordinately glucose regulated in MIN6 cells,
      whereas that of the exopeptidase, carboxypeptidase H, was unaffected by glucose.
      Proinsulin, PC2 and PC3 biosynthesis was specifically stimulated over that of
      total MIN6 cell protein synthesis above a threshold of 4 mmol/l glucose that
      reached a maximum rate between 8 and 10 mmol/l glucose. Glucose-induced
      proinsulin, PC2, and PC3 biosynthesis was rapid (occurring after a 20-min lag
      period but reaching a maximum by 60 min), unaffected by the presence of
      actinomycin D; and in parallel experiments, stimulatory glucose concentrations
      did not alter MIN6 cell total preproinsulin, PC2, or PC3 mRNA levels. Thus, short
      term (< 2 h) glucose stimulation of proinsulin, PC2 and PC3 biosynthesis in MIN6
      cells, like that in isolated islets, was mediated at the translational level.
      Intracellular signals for mediating glucose-stimulated proinsulin PC2 and PC3
      biosynthesis translation in MIN6 cells also appeared to be similar to those in
      pancreatic islets, requiring glucose metabolism and a supporting role for protein
      kinase A. However, protein kinase C or a Ca(2+)-dependent protein kinase did not
      appear to be required for glucose-regulated proinsulin biosynthesis in MIN6
      cells, as in islets. MIN6 cells are the first beta-cell line that indicate
      glucose-regulated proinsulin biosynthesis translation essentially identical to
      that in differentiated islet beta-cells and will be an important experimental
      model to better define the mechanism of proinsulin biosynthesis in detail.

PMID- 8522058
TI  - Effect of prostaglandin E2 and hyaluronan on mesangial cell proliferation. A
      potential contribution to glomerular hypercellularity in diabetes.
AB  - Proliferation of mesangial cells is a feature of several forms of human and
      experimental glomerulopathy, including that seen in diabetes. The nonsulfated
      glycosaminoglycan hyaluronan participates in the regulation of pericellular
      matrix assembly and is a mitogen in some cell types. We have shown previously
      that hyaluronan production is increased in the glomerulus in a glucose- and
      prostaglandin-dependent manner. We have investigated the effect of diabetes and
      of addition of hyaluronan and prostaglandin E2 (PGE2) on the uptake of
      [3H]thymidine by glomerular core preparations enriched in mesangial cells. When
      compared with nondiabetic controls, it was shown that [3H]thymidine uptake was
      significantly increased in glomerular core preparations from streptozotocin
      induced diabetic rats (to 169 +/- 5%, P < 0.001). In glomerular cores from both
      experimental groups, hyaluronan (50-250 ng/ml) or PGE2 (10(-12) to 10(-8) mol/l)
      increased the uptake of [3H]thymidine. Further, mesangial cells from nondiabetic
      control glomerular cores, when maintained in culture in early passage, responded
      with increased [3H]thymidine uptake to raised glucose (5.6-25 mmol/l) and to
      added hyaluronan and PGE2. We propose that prostaglandin and hyaluronan
      production in response to a raised glucose environment in diabetes can contribute
      to mesangial hypercellularity.

PMID- 8522059
TI  - Effect of puberty on markers of glomerular hypertrophy and hypertension in IDDM.
AB  - Epidemiological data implicate puberty as a factor in the initiation of diabetic
      nephropathy. However, the mechanism remains unclear. We hypothesized that puberty
      would result in an increase in glomerular hypertrophy and hypertension; these two
      early concomitant events are seen as pivotal to the pathophysiology of diabetic
      nephropathy. We studied the effect of pubertal duration on three surrogate
      markers of glomerular hypertrophy/hypertension: kidney volume (KV),
      microalbuminuria (MA), and Na-Li countertransport (CT). We recruited 177 subjects
      (87 female and 90 male; aged 6.2-22.1 years) with IDDM of 5 to 10 years' duration
      (6.8 +/- 1.6 years) into three groups with different pubertal duration:
      prepubertal since IDDM diagnosis; prepubertal at diagnosis, now pubertal; or
      early puberty at diagnosis, now postpubertal. KV was measured by ultrasound and
      corrected for body surface area; MA was defined as urinary albumin excretion of
      15-200 micrograms/min in two of three 24-h samples, and Na-Li CT was measured in
      erythrocytes. As pubertal duration increased, there was a disproportionate
      increase in mean KV (prepubertal, 247 +/- 6 [SE] ml/1.73 m2; pubertal, 282 +/-
      7/1.73 m2; postpubertal, 295 +/- 7/1.73 m2, P = 0.001), prevalence of
      nephromegaly (KV > 300 ml/1.73 m2) (14, 31, and 45%, respectively, P = 0.001),
      and prevalence of MA (0, 9.7, and 20.5%, respectively, P = 0.003). Subjects with
      KV > 300 ml/1.73 m2 were eight times more likely to have MA than those with KV <
      300 (odds ratio 8.1, 95% confidence interval 2.4-27.4, P = 0.0001). There was no
      effect of pubertal duration on Na-Li CT. Multiple regression with KV as the
      dependent variable found an association with pubertal duration, MA, Na-Li CT, and
      current HbA1c (P < 0.0001). Our findings indicate that pubertal duration is an
      important determinant of both KV and MA and suggest that nephromegaly precedes
      microalbuminuria. We postulate that these effects are attributable to the
      influence of the pubertal milieu on glomerular hypertrophy/hypertension.

PMID- 8522060
TI  - Galactosemic neuropathy in transgenic mice for human aldose reductase.
AB  - We studied the functional consequences of an enhanced polyol pathway activity,
      elicited with galactose feeding, on the peripheral nerve of transgenic mice
      expressing human aldose reductase. Nontransgenic littermate mice were used as
      controls. With a quantitative immunoassay, the expression level of human aldose
      reductase in the sciatic nerve was 791 +/- 44 ng/mg protein (mean +/- SE), about
      25% of that in human sural nerve. When the transgenic mice were fed food
      containing 30% galactose, significant levels of galactitol accumulated in the
      sciatic nerve. Galactose feeding of nontransgenic littermate mice led to a 10
      fold lower accumulation of galactitol. Galactose feeding for 16 weeks caused a
      significant and progressive decrease in motor nerve conduction velocity in
      transgenic mice to 80% of the level of galactose-fed littermate mice, which was
      not significantly different from that of galactose-free littermate mice. A
      morphometric analysis of sciatic nerve detected > 10% reduction of mean
      myelinated fiber size but no alterations of myelinated fiber density in galactose
      fed transgenic mice compared with other groups. The functional and structural
      changes that develop in galactose-fed transgenic mice are similar to those
      previously reported in diabetic animals. The results of these studies suggest
      that transgenic mice expressing human aldose reductase may be a useful model not
      only for defining the role of the polyol pathway in diabetic neuropathy but also
      for identifying and characterizing effective inhibitors specific for human aldose
      reductase.

PMID- 8522061
TI  - The antihyperglycemic agent englitazone prevents the defect in glucose transport
      in rats fed a high-fat diet.
AB  - The effects of englitazone in male Wistar rats fed a high-fat diet (59% of
      calories as fat) were compared with control rats fed a high-carbohydrate diet
      (69% of calories as carbohydrate) (5-15 animals per group). Insulin-stimulated
      (17 nmol/l) 2-deoxy-D-glucose (2-DG) uptake was inhibited 31% in adipocytes
      isolated from rats on the high-fat diet for 3 weeks, but englitazone (50 mg/kg
      for the last 7 days) normalized the response. There was a selective decrease in
      GLUT4 (54 +/- 5% of high-carbohydrate) in epididymal fat from rats on the high
      fat diet for 3 weeks, but englitazone treatment did not reverse the defect in
      GLUT4 (43 +/- 8% of high-carbohydrate) or increase GLUT1 (81 +/- 12% of high
      carbohydrate). Englitazone normalized oral glucose (1 g/kg body wt) intolerance
      and excessive (210% of high-carbohydrate) liver glycogen deposition (from
      [14C]glucose) caused by the high-fat diet. The high-fat diet tended to decrease
      insulin receptor substrate-1 (IRS-1) and phosphatidylinositol-3'-kinase (PI-3
      kinase) expression in epididymal fat (26% decrease; P < 0.1). Englitazone did not
      reverse this decrease in IRS-1 and PI-3-kinase levels in fat from high-fat-fed
      rats (there was a further 25-30% decrease, P < 0.05), nor did it increase PI-3
      kinase activity in 3T3-L1 adipocytes under conditions (48 h incubation) where it
      stimulated 2-DG uptake sixfold or enhanced insulin-stimulated 2-DG uptake. In
      summary, englitazone prevented the insulin resistance associated with a high-fat
      diet, but the mechanism of action does not involve changes in fat or muscle
      glucose transporter content and may not involve activation of the insulin
      signaling pathway via PI-3-kinase.

PMID- 8522062
TI  - Pancreatic regenerating gene overexpression in the nonobese diabetic mouse during
      active diabetogenesis.
AB  - The reg gene has previously been shown to be associated with regeneration of
      pancreatic islets. Strategies for influencing the replication and the growth of
      the beta-cell mass may be important for prevention and/or treatment of type I
      diabetes. In this study, we have examined the level of reg gene expression at
      various degrees of diabetogenesis in the pancreas of the NOD mouse (male, female,
      and cyclophosphamide-treated male) using both human reg cDNA as the probe and dot
      blot analysis. The expression of the reg gene was found to be significantly
      increased in female mice compared with male mice, and in both cases, the
      expression level was not influenced by age. Nondiabetic female mice have a
      significantly higher expression of the gene than diabetic female mice, and there
      was a positive correlation between the age of diabetes onset and the reg mRNA
      level. In addition, overexpression of the reg gene was found in male mice treated
      by cyclophosphamide, an agent known to be a potent inducer of diabetes in male
      NOD mice. None of these results were found in the diabetes-resistant control OF1
      mice, in which pancreatic reg gene expression did not differ between female and
      male mice treated or untreated with cyclophosphamide. All of these data suggest
      that there is a strong correlation between reg gene expression in the pancreas of
      the NOD mouse and the likelihood of developing diabetes.

PMID- 8522063
TI  - Pathogenic and protective roles of CD45RB(low) CD4+ cells correlate with cytokine
      profiles in the spontaneously autoimmune diabetic mouse.
AB  - The adoptive transfer of splenocytes from diabetic NOD mice to NOD-scid/scid (NOD
      scid) recipients results in diabetes. This model was used to test the effect of
      cotransfer of splenocyte subsets from young nondiabetic NOD mice. As shown
      previously in other NOD models, the CD4+ subset from young nondiabetic mice
      significantly delayed the onset of diabetes in splenocyte cotransfers (P <
      0.001). The data presented here showed that the development of diabetes in NOD
      scid recipients correlated with a rapid increase in peripheral CD45RB(low) CD4+
      cells. However, the CD45RB(low) subset of CD4+ cells from young nondiabetic mice
      protected from diabetes transfer in this model. We therefore examined whether
      CD45RB(low) CD4+ cells from diabetic mice were pathogenic rather than protective.
      CD45RB(low) CD4+ splenocytes from diabetic NOD mice were transferred along with
      CD8+ splenocytes from diabetic mice into NOD-scid recipients, and all of the
      recipients became diabetic within 5 weeks posttransfer. In contrast, no
      recipients (0 of 10) of CD45RB(high) CD4+ cells along with CD8+ splenocytes from
      diabetic mice became diabetic within 5 weeks posttransfer (P < 0.001). A
      correlate for the difference between CD45RB(low) CD4+ cells from diabetic NOD
      mice and CD45RB(low) CD4+ cells from nondiabetic mice, which showed protective
      effect in splenocyte cotransfers, was found in cytokine production after
      stimulation with anti-CD3 antibodies in vitro. CD45RB(low) CD4+ cells from
      diabetic mice showed a significantly higher ratio (approximately fivefold) of
      gamma-interferon (IFN-gamma) to interleukin (IL)-4 when compared with CD45RB(low)
      CD4+ cells from nondiabetic mice (P < 0.001). In conclusion, the function of the
      CD45RB(low) population of CD4+ cells changes from a protective to a pathogenic
      one during the development of disease in the NOD mouse. This change in function
      correlates with cytokine production in vitro; increased IFN-gamma-to-IL-4 ratio
      is associated with pathogenic potential and occurs coincident with (or after) the
      onset of diabetes.

PMID- 8522064
TI  - Effect of risk factors on exercise capacity in NIDDM.
AB  - Exercise capacity has been used as a noninvasive parameter for predicting
      cardiovascular events. It is known that diabetic patients have an impaired
      exercise capacity when compared with nondiabetic age-matched control subjects,
      but the risk factors associated with this impairment have not been thoroughly
      analyzed. A total of 453 male and female NIDDM patients who underwent graded
      exercise testing with expired gas analysis were studied to determine the possible
      influences of demographic and cardiac risk factors on exercise capacity.
      Univariate and multiple linear regression analyses were performed on baseline
      patient characteristics with respect to peak oxygen consumption (VO2). In the
      regression analyses, African-American race was strongly associated with a
      decrease in peak VO2; the difference in means between African-Americans and other
      subjects for men was -2.50 ml.kg-1.min-1 (-4.28, -0.07, 95% CI) (P < 0.006) and
      for women was -2.96 ml.kg-1.min-1 (-4.45, -1.47) (P < 0.0002). Univariate
      analyses revealed that African-American subjects had increased prevalence, longer
      duration, and higher systolic and diastolic hypertension than the non-Hispanic
      and Hispanic whites. Other independent predictors of peak VO2 (reported as change
      in peak VO2 in milliliters per kilogram per minute) were BMI (men: -0.39 kg/m2 [
      0.52, -0.29], P < 0.0001; women: -0.39 kg/m2 [-0.48, -0.31], P < 0.0001), age
      (men: -0.16/year [-0.23, -0.09], P < 0.0001; women: -0.17/year [-0.24, -0.11], P
      < 0.0001), baseline resting systolic blood pressure (men: -0.03/mmHg [-0.06, 
      0.01], P < 0.05; women: -0.03/mmHg (-0.06, -0.01)f1p4< 0.05), and pack-years
      smoking (men: -0.04/pack-years [-0.04, -0.01], P < 0.01; women: -0.04/pack-years
      [-0.07, -0.01], P < 0.0001). Thus, in this large NIDDM study, weight loss,
      smoking cessation, and aggressive blood pressure control, particularly in African
      Americans with NIDDM, would appear to be important in improving exercise capacity
      and potentially improving the increased cardiovascular mortality associated with
      an impaired exercise capacity.

PMID- 8522065
TI  - Insulin transport from plasma into the central nervous system is inhibited by
      dexamethasone in dogs.
AB  - We have previously shown that transport of plasma insulin into the central
      nervous system (CNS) is mediated by a saturable mechanism consistent with insulin
      binding to blood-brain barrier insulin receptors and subsequent transcytosis
      through microvessel endothelial cells. Since glucocorticoids antagonize insulin
      receptor-mediated actions both peripherally and in the CNS, we hypothesized that
      glucocorticoids also impair CNS insulin transport. Nine dogs were studied both in
      the control condition and after 7 days of high-dose oral dexamethasone (DEX)
      administration (12 mg/day) by obtaining plasma and cerebrospinal fluid (CSF)
      samples over 8 h for determination of immunoreactive insulin levels during a 90
      min euglycemic intravenous insulin infusion (plasma insulin approximately 700
      pmol/l). From these data, the kinetics of CNS insulin uptake and removal were
      determined using a mathematical model with three components (plasma-
      >intermediate compartment, hypothesized to be brain interstitial fluid-->CSF).
      DEX increased basal insulin levels 75% from 24 +/- 6 to 42 +/- 30 pmol/l (P <
      0.005) and slightly increased basal glucose levels from 5.0 +/- 0.7 to 5.3 +/-
      1.0 mmol/l (P < 0.05). DEX also lowered the model rate constant characterizing
      CNS insulin transport by 49% from 5.3 x 10(-6) +/- 4.0 x 10(-6) to 2.7 x 10(-6)
      +/- 1.2 x 10(-6) min-2 (P < or = 0.001). As glucocorticoids are known to reduce
      CSF turnover, we also hypothesized that the model rate constant associated with
      CSF insulin removal would be decreased by DEX. As expected, the model rate
      constant for CSF insulin removal decreased 47% from 0.038 +/- 0.013 to 0.020 +/-
      0.088 min-1 (P < or = 0.0005) during DEX treatment. We conclude that DEX impairs
      CNS insulin transport. This finding supports our hypothesis that insulin
      receptors participate in the CNS insulin transport process and that this process
      may be subject to regulation. Moreover, since increasing brain insulin transport
      reduces food intake and body adiposity, this observation provides a potential
      mechanism by which glucocorticoid excess leads to increased body adiposity.

PMID- 8522066
TI  - Recombinant human insulin-like growth factor I increases insulin sensitivity and
      improves glycemic control in type II diabetes.
AB  - Insulin resistance is a major factor in the pathophysiology of type II diabetes
      and a major impediment to successful therapy. The identification of treatments
      that specifically target insulin resistance could improve diabetes management
      significantly. Since IGFs exert insulin-like actions and increase insulin
      sensitivity when administered at supraphysiological doses, we determined the
      effect of 6 weeks of recombinant human IGF-I (rhIGF-I) administration on insulin
      resistance and glycemic control in obese insulin-resistant patients with type II
      diabetes. A total of 12 patients with type II diabetes were recruited for the
      study. Subcutaneous administration of rhIGF-I (100 micrograms/kg b.i.d.)
      significantly lowered blood glucose. Fructosamine declined from 369 to 299
      mumol/l by 3 weeks of administration and then declined further to 271 at the end
      of 5 weeks. Glycosylated hemoglobin, which was 10.4% pretreatment, declined to
      8.1% at the end of therapy. Mean 24-h blood glucose during a modal day was 14.71
      +/- 4.5 mmol/l pretreatment and declined to 9.1 +/- 3.21 mmol/l by the end of
      treatment. These improvements in glycemia were associated with a decrease in
      serum insulin levels. Mean insulin concentrations declined from 108.0 to 57.0
      pmol/l during the modal day measurements and from 97.2 to 72.0 pmol/l during the
      mixed-meal tolerance test. Changes in glycemia were accompanied by a marked
      increase in insulin sensitivity. The insulin sensitivity index (SI) calculated
      from a frequently sampled intravenous glucose tolerance test (FSIVGTT) after the
      method of Bergman et al. (Bergman RN, Finegold DT, Ader M: Assessment of insulin
      sensitivity in vivo. Endocr Rev 6:45-86, 1985) increased 3.4-fold. Furthermore,
      the improvement in glycemic control was accompanied by a change in body
      composition with a 2.1% loss in body fat as calculated by dual energy x-ray
      absorptiometry without change in total body weight. Significant side effects were
      present in some subjects, although nine subjects were able to complete at least
      4.5 weeks of the protocol and six subjects completed the entire 6 weeks.
      Supraphysiological IGF-I concentrations were maintained throughout the study,
      increasing from 206 micrograms/l in the control period to 849 micrograms/l at the
      end of 6 weeks of rhIGF-I treatment. The increase in IGF-I levels was accompanied
      by a significant increase in IGF binding protein-2 levels, a slight reduction in
      IGF binding protein-3 levels, and an increase in levels of IGF binding protein-1.
      In summary, IGF-I significantly lowered blood glucose as reflected by short-term
      and long-term indexes of glycemic control and increased insulin sensitivity. It
      remains to be determined whether a dosage can be administered that avoids
      significant side effects and still achieves reasonable glycemic control.

PMID- 8522067
TI  - Rapid ras-oncogene-mediated transformation maintains steroidogenic
      differentiation in adrenocortical parenchymal cells.
AB  - While its action as a transforming agent is well known, expression of the ras
      oncogene may also alter tissue-specific differentiation. We have been examining
      the relationship of transformation and differentiation in steroidogenic cells of
      the rat. Infection of adrenocortical zona glomerulosa (GLOM) cells with the v-Ki
      ras containing Kirsten murine sarcoma virus did not induce focus formation.
      Instead, diffuse cellular multilayers formed from which loosely adherent,
      refractile cells emerged. After selective passaging these refractile cells,
      designated KiGLOM, were morphologically transformed, had reduced serum
      requirements for growth, greatly increased saturation densities, and they rapidly
      formed tumours in immunosuppressed hosts. In addition, under conditions where
      normal cells were no longer steroidogenic (ie. after passaging), KiGLOM cells
      expressed the steroid-specific cholesterol side chain cleavage cytochrome P
      450scc and they produced significant, albeit reduced, amounts of corticosterone
      in comparison with primary GLOM cultures. Additionally, trophic hormone treatment
      increased steroid production in Ki-GLOM cells and this increase was partially
      reversed by lovastatin, a pharmacological inhibitor of ras p21 function. Thus,
      after a morphological selection that removed normal neighbours, v-Ki ras infected
      cells transformed rapidly while remaining steroidogenic. These results, combined
      with previous reports of steroidogenic v-Ki ras transformed adrenocortical
      fibroblasts and ovarian granulosa cells suggest that the ability of the ras
      oncogene to co-opt signal transduction pathways associated with both growth and
      differentiation is a common feature of the steroidogenic phenotype.

PMID- 8522068
TI  - Maintenance of cell-type-specific cytoskeletal character in epithelial cells out
      of epithelial context: cytokeratins and other cytoskeletal proteins in the rests
      of Malassez of the periodontal ligament.
AB  - We have determined the patterns of synthesis of cytokeratins and other epithelial
      marker proteins in the "rests of Malassez" of the periodontium of rabbits and
      humans, by immunofluorescence microscopy of cryosections prepared from fixed and
      decalcified rabbit teeth with attached ligament or from manually isolated human
      periodontal ligaments. Proteins of the major cell structures characterizing
      epithelial differentiation are present in Malassez cells: a complex set of
      cytokeratins as well as desmosomal, hemidesmosomal and basal lamina proteins. In
      addition, we have shown these cytoskeletal and extracellular matrix structures by
      electron microscopy. The cytokeratin complement of Malassez cells was found to be
      highly complex, as 8 of the total of 20 known epithelial cytokeratins were
      detected (nos. 5, 7, 8, 14, 15, 17, 18, 19). This pattern, together with the
      presence of the desmosomal cadherins Dsg2 and Dsc2 and the cytoplasmic desmosome
      plaque-associated protein plakophilin 1, indicates that the cells of the rests of
      Malassez are derived from the basal cell layer of a stratified squamous
      epithelium rather than from simple epithelial or neuroendocrine epithelial cells.
      Our observations show that Malassez cells retain the major characteristics of
      epithelial cells throughout their differentiation from the root sheath epithelium
      into the rests of Malassez, even though the surface location and the polar tissue
      architecture that typify epithelial are lost during this process. From this study
      we further conclude that the specific cytoskeletal complement of the Malassez
      cells represents an intrinsic gene expression program that neither depends on nor
      causes the formation of a stratified epithelium. We also compare the specific
      cytoskeletal features of Malassez cells with those of other persisting epithelial
      residues and discuss the potential value of these findings in relation to the
      histogenesis and diagnostic classification of dental and periodontal cysts and
      tumors.

PMID- 8522069
TI  - Two stages of enteropathogenic Escherichia coli intestinal pathogenicity are up
      and down-regulated by the epithelial cell differentiation.
AB  - Pathogens and eucaryotic cells are active partners during the process of
      pathogenicity. To gain access to enterocytes and to cross the epithelial
      membrane, many enterovirulent microorganisms interact with the brush border
      membrane-associated components as receptors. Recent reports provide evidence that
      intestinal cell differentiation plays a role in microbial pathogenesis. Human
      enteropathogenic Escherichia coli (EPEC) develop their pathogenicity upon
      infecting enterocytes. To determine if intestinal epithelial cell differentiation
      influences EPEC pathogenicity, we examined the infection of human intestinal
      epithelial cells by JPN 15 (pMAR7) [EAF+ eae+] EPEC strain as a function of the
      cell differentiation. The human embryonic intestinal INT407 cells, the human
      colonic T84 cells, the human undifferentiated HT-29 cells (HT-29 Std) and two
      enterocytic cell lines, HT-29 glc-/+ and Caco-2 cells, were used as cellular
      models. Cells were infected apically with the EPEC strain and the cell
      association and cell-entry were examined by quantitative determination using
      metabolically radiolabeled bacteria, as well as by light, scanning and
      transmission electron microscopy. [EAF+ eae+] EPEC bacteria efficiently colonized
      the cultured human intestinal cells. Diffuse bacterial adhesion occurred to
      undifferentiated HT-29 Std and INT407 cells, whereas characteristic EPEC cell
      clusters were observed on fully differentiated enterocytic HT-29 glc-/+ cells and
      on colonic crypt T84 cells. As shown using the Caco-2 cell line, which
      spontaneously differentiates in culture, the formation of EPEC clusters increased
      as a function of the epithelial cell differentiation. In contrast, efficient cell
      entry of [EAF+ eae+] EPEC bacteria occurred in recently differentiated Caco-2
      cells and decreased when the cells were fully differentiated.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8522070
TI  - Localization of alpha 4m integrin at sites of mesenchyme condensation during
      embryonic mouse development.
AB  - The expression and distribution of the murine alpha 4 (alpha 4m) integrin subunit
      and of one of its ligands, VCAM-1, were examined in the developing mouse embryo
      at different development stages. Transcription of the mRNA was investigated by in
      situ hybridization using single-stranded sense and anti-sense cDNA probes and by
      Northern blotting. In parallel sections integrin was identified by
      immunohistochemistry using the alpha 4m-specific antibody R1/2. In general both
      methods gave similar distributions. The results demonstrate that alpha 4m and
      vascular cell adhesion molecule-1 (VCAM-1) are expressed in mouse embryonic liver
      (E11-E15) and are developmentally down-regulated, consistent with the
      haematopoietic properties of embryonic liver. Developmental-stage-dependent
      expression of alpha 4m was also observed in lymphoid organs, such as spleen and
      thymus, and in some non-lymphoid organs or tissues, such as skeletal and tongue
      muscles, smooth muscles of the blood vessels, the outflow tract of the embryonic
      heart, the papilla of the tooth, the glomeruli of the kidney and the stroma of
      the gonads. In the latter tissues, the expression of alpha 4m correlated with the
      transient condensation of particular mesenchymal structures. We also confirm that
      VCAM-1 and alpha 4 beta 1 are co-distributed only in some tissues, suggesting
      that during mouse development, VLA-4 interacts mainly with another ligand,
      probably fibronectin.

PMID- 8522071
TI  - Retinoic acid affects basement membrane formation of the seminiferous cords in 14
      day male rat gonads in vitro.
AB  - The vitamin A derivative retinoic acid (RA) has been previously shown to have
      teratogenic effects and an ability to modulate cell differentiation in vivo and
      in vitro. In this study bilateral testicular primordia with the mesonephroi
      attached were isolated from rat fetuses at 14.5 days of gestation. The gonads
      were cultured on agar-coated grids in a synthetic medium. RA was added to male
      rat embryonic gonad cultures at a final concentration of 10(-6) M for 3 h. Two
      types of controls were prepared: (1) by omitting RA from the culture medium
      (alcohol controls) and (2) by using plain medium (untreated controls). When
      applied to gonad cultures RA was found to affect basement membrane development
      and disturb the general appearance of the tissue. All controls exhibited normal
      morphology. In order to evaluate the morphological changes observed due to the RA
      treatment, constituents of the basement membrane, laminin and collagen IV, were
      localized immunohistochemically at the light microscope level. Basement membrane
      was also studied at the electron microscope level in control and RA-treated
      cultures. We propose that one of the effects RA has on rat testicular
      morphogenesis is the irreversible suppression of seminiferous cord basement
      membrane formation and the disruption of normal testicular morphogenesis.

PMID- 8522073
TI  - Feedback of obstetrical outcomes as an educational tool.

PMID- 8522072
TI  - Maturation-dependent changes in the regulation of liver-specific gene expression
      in embryonal versus adult primary liver cultures.
AB  - During rat liver development, which starts on day 10 of embryogenesis (E10), and
      until E15, all parenchymal cells are thought to be a homogeneous population of
      bipotential progenitors, able to give rise to both hepatocytes and bile duct
      epithelial cells. We established primary liver cultures from embryonic livers at
      various developmental stages, from E14 to neonates, as well as adult rats. Gene
      expression and regulation by three known differentiating agents, heparin,
      dimethylsulfoxide (DMSO), and sodium butyrate, were examined in these primary
      cultures. Alpha-fetoprotein (alpha-FP), albumin, gamma-glutamyltranspeptidase
      (GGT), and glutathione-S-transferase-P (Yp) were expressed by cultured liver
      cells through fetal development, whereas insulin-like growth factor-II (IGF II)
      receptor, expressed in fetal parenchymal cells, was not present in cultured
      neonatal cells. Heparin increased alpha-FP levels in fetal liver cells, but not
      in cells obtained after birth. The expression of GGT and Yp was coordinately
      regulated. The two genes were up-regulated by sodium butyrate and down-regulated
      by DMSO in cultured liver cells from all embryonal ages tested. However, the
      regulation of these two genes by sodium butyrate and DMSO was not apparent in
      neonatal and adult liver cultures. Sodium butyrate increased alpha-FP and albumin
      mRNA expression in E14 and E15 cells, but not in E16, neonatal or adult cultures,
      and its addition caused heterogenous expression of albumin. We conclude that the
      regulation of gene expression in primary liver cultures by the three agents
      tested is altered after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522074
TI  - Depression in mothers.

PMID- 8522075
TI  - A near-perfect death.

PMID- 8522076
TI  - New law in California.

PMID- 8522077
TI  - Uncommon teaching of common problems.

PMID- 8522078
TI  - Entry of US medical school graduates into family practice residences: 1994-1995
      and 3-year summary.
AB  - This is the 14th report prepared by the American Academy of Family Physicians
      (AAFP) on the percentage of each US medical school's graduates entering family
      practice residency programs. Approximately 13.4% of the 15,620 graduates of US
      medical schools between July 1993 and June 1994 were first-year family practice
      residents in October 1994, compared with 12.3% the previous year. This is the
      highest percentage since 1980-1981, when this series of studies began. Medical
      school graduates from publicly funded medical schools were almost twice as likely
      to be first-year family practice residents in October 1993 than were residents
      from privately funded schools, 16.4% compared with 9.0%. The West North Central
      region reported the highest percentage of medical school graduates who were first
      year residents in family practice programs in October 1994 at 20.1%; the Middle
      Atlantic and New England regions continued with the lowest percentages at 7.5%
      and 8.7%, respectively. At least one in four graduates from 12 medical schools
      during the reporting period was in a family practice residency program in October
      1994, compared with nine in October 1993 and only two medical schools in 1992.
      Approximately one in two medical school graduates entering a family practice
      residency program as first-year residents in October 1994 entered a program in
      the same state where they graduated from medical school. The percentages for each
      medical school have varied substantially from year to year since the AAFP began
      reporting this information. The average percentage for each medical school for
      the last 3 years is reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522079
TI  - Results of the 1995 National Resident Matching Program: family practice.
AB  - The 1995 National Resident Matching Program (NRMP) results broke records in the
      number of positions filled in family practice residencies, with an increase of
      11.8% over 1994 figures (2,563 vs 2,293) and an increase of 12.5% in positions
      filled with US seniors (2,081 vs 1,850). This is the largest number of US seniors
      choosing family practice in the NRMP's history. In keeping with the trend that
      began in 1992, 7% more positions were filled on July 1, 1995, than were filled at
      the same time in 1994 (3,252 vs 3,040). Internal medicine residencies matched 74
      more US seniors in 1995, and pediatric residencies matched 84 more US seniors.
      Given the anticipated career choices of students entering residency training in
      the generalist disciplines (95% of students matching in family practice, 60% of
      students matching in pediatrics, and 45% of students matching in internal
      medicine), it is expected that 33.5% of the class of 1995 (Liaison Committee on
      Medical Education-accredited medical schools) will practice as generalists. First
      year positions offered in family practice through the NRMP increased 6%, and the
      number of Accreditation Council on Graduate Medical Education-accredited family
      practice residency programs increased 3% (421 vs 410). With continued increased
      interest in family practice as a career choice and the need for more family
      physicians, support for the nation's family practice residency programs continues
      to be of critical importance.

PMID- 8522080
TI  - Effectiveness and safety of esophagogastroduodenoscopy in family practice:
      experience at a university medical center.
AB  - BACKGROUND AND OBJECTIVES: As the use of esophagogastroduodenoscopy (EGD) by
      family physicians increases, a need exists to further demonstrate the procedure's
      clinical effectiveness and safety and the general experience of family physicians
      performing the procedure. This study examines the general experience of a group
      of family physicians performing EGDs in the university setting. METHODS: An
      analysis was done of all patients undergoing EGDs performed by family physicians
      at a university hospital during a consecutive 27-month period. Demographics,
      indications, findings, diagnoses, therapy, complications, and biopsies were
      analyzed. Clinical effectiveness was measured by recording whether an EGD
      resulted in changes in diagnosis, medical therapy, or clinical management.
      Endoscopic diagnoses also were correlated with biopsy pathological diagnoses.
      RESULTS: During the study period, 188 EGDs were performed. Clinical management of
      patients was changed in 88.6% of cases. The diagnosis was changed in 81.8% of
      cases, and drug therapy was changed in 55.7% of cases. Endoscopic impressions
      were confirmed by biopsy in 93.2% of cases. Procedures were completed in 98.3% of
      cases with no complications. CONCLUSIONS: This study demonstrates the clinical
      effectiveness of EGDs performed by family physicians. The feasibility of family
      practice endoscopy in the university medical center setting has been
      demonstrated, and continued benefits from this practice are anticipated.

PMID- 8522081
TI  - Family practice residents' maternity leave experiences and benefits.
AB  - BACKGROUND: A growing number of residents are having babies during residency
      training. While many businesses are working to improve maternity conditions and
      benefits for their employees, residency programs are often not prepared to
      accommodate pregnant residents. This study was conducted to examine the maternity
      leave experiences of women who delivered infants during their family practice
      residency training. METHODS: Program directors from each of the 394 family
      practice residency programs listed in the 1993 Directory of Family Practice
      Residency Programs were asked to distribute surveys to female residents who gave
      birth during their residency training and had returned to work by the time of the
      study. RESULTS: Of 199 known eligible residents, 171 (86%) completed surveys;
      these women represented 127 programs located in 36 states and Puerto Rico. Only
      56.8% of women were aware of their program having a written maternity leave
      policy. The average length of maternity leave was 8 weeks; 76% had leaves of 10
      weeks or less. For many, the maternity leave was derived from more than one
      source, including vacation, sick time, or a mother-child elective. Nearly all
      (88.3%) the women breast-fed, and the mean duration of breast-feeding was more
      than 19 weeks. In general, participants believed that having a baby during
      residency was somewhat difficult. Problems frequently encountered by women after
      their return to work included sleep deprivation and tiredness, difficulty
      arranging for child care, guilt about child care, and breast-feeding. Factors
      that detracted most from the childbirth experience were too little sleep,
      problems arranging for child care, and lack of support from the partner,
      residency faculty, and other residents. CONCLUSIONS: Having a baby during
      residency is somewhat difficult for the average female resident. Factors that may
      ease this difficulty include getting adequate sleep and receiving support from
      one's partner, faculty, and other residents.

PMID- 8522082
TI  - Do we practice what we preach? Comparing the patients of faculty and residents.
AB  - BACKGROUND AND OBJECTIVES: In academic family practice centers, the distribution
      of patients between faculty and residents influences the educational milieu. The
      medical literature has rarely addressed the differential case mix within the
      ambulatory medical educational setting. The goal of this study was to compare the
      characteristics of patient visits to resident and faculty physicians in seven
      community-based, university-affiliated family practice programs. METHODS: Using
      the National Ambulatory Care Survey instrument and protocol, 98 faculty and
      resident physicians recorded their ambulatory patient visits for one randomly
      selected week between July 1991 and June 1992 (n = 1,498). RESULTS: Patients of
      resident physicians were younger, more likely to be nonwhite (21.7% vs 9.8%, P <
      .001), and more likely to be reimbursed by Medicaid (34.2% vs 14.3%, P < .001)
      than patients of faculty physicians. Despite these patient differences, the
      spectrum of clinical problems was similar. There were minimal differences in the
      delivery of diagnostic services and therapeutic services. CONCLUSIONS: The
      patients seen by residents and faculty differ in important demographic
      characteristics. These differences could adversely affect the education of
      resident physicians. Academic family practice centers should actively monitor the
      age/gender/payment profile of resident and faculty patient panels and assign
      patients to achieve a desirable case mix for resident education. The differential
      racial distribution of faculty and resident visits suggests an unidentified
      systematic bias in patient assignment that warrants further investigation.

PMID- 8522083
TI  - After-hours telephone calls in a family practice residency: volume, seriousness,
      and patient satisfaction.
AB  - BACKGROUND: After-hours calls are common in primary care physicians' practices.
      Calls may be unnecessary from the physician's perspective, but patients may have
      a different concept of the importance of reaching their physician immediately.
      This study's purpose was to compare physician and patient perceptions of the same
      telephone call episode. METHODS: Family practice residents (n = 19) recorded all
      patient-initiated after-hours telephone contacts (n = 192) during July 1993.
      Study personnel then telephoned, within 1 week of their call, the patients who
      made the calls. Patients were asked about the reason for their call, its
      seriousness, and their satisfaction with the handling of their problem. RESULTS:
      During the study month, 1.1 after-hours calls were received for every 10 office
      visits. A substantial minority of patients (29%) rated their problems in the
      highest severity category, while physicians assigned only 8% of calls the highest
      severity rating. The majority of patients (76.7%) were satisfied with how their
      after-hours calls were handled. CONCLUSIONS: In matched cases, physicians and
      patients perceive about the same proportion of calls to be routine versus more
      severe. Although patient satisfaction was high, further research into causes of
      dissatisfaction is needed.

PMID- 8522084
TI  - Payment and attendance at general practice preventive health examinations.
AB  - BACKGROUND AND OBJECTIVES: This study's purpose was to determine how conditions
      of payment influence attendance at preventive health examinations. METHODS: A
      multi-practice study of 65 general practitioners (GPs) was conducted in two areas
      in the county of Aarhus, Denmark. The GPs invited 2,452 men aged 40-49 to a
      preventive health examination for coronary heart disease (CHD). The examination
      was free in one area but cost $40 in the other area. A risk profile was
      estimated, based on a summation of points for risk factors for CHD, including
      blood pressure, serum cholesterol, smoking behavior, body mass index, and family
      history of CHD. RESULTS: Attendance at the examinations was 37% in the required
      payment area and 66% in the free area. Of the total attenders, 13% had an
      increased risk of CHD. A slight but significant tendency, a lower risk for
      developing CHD, existed among attenders who paid for the examination. CONCLUSION:
      A requirement for payment for health examination leads to fewer patients
      obtaining examinations.

PMID- 8522085
TI  - The future of procedural training in family practice residency programs: look
      before you LEEP.
AB  - Procedural training is a tremendously important issue and has implications for
      what and how we teach family physicians. Should we continue with an increasingly
      densely packed longitudinal model of training, or do we move to a more explicitly
      structured block design? Should our decisions be guided by community needs,
      marketplace demands, or available technology? Finally, and most importantly, how
      can we determine the performance quality of the procedures we choose to perform
      and teach? Each of these questions calls for an extended dialogue among
      practicing family physicians, family physician educators, and those who
      participate in--and pay for--primary health care. It is clearly time for this
      dialogue to begin in earnest.

PMID- 8522086
TI  - [5th Training workshop in hepato-gastroenterology. Paris, 18-19 November 1994].

PMID- 8522087
TI  - [Strategy for hemostatic treatment of hemorrhages caused by rupture of esophageal
      and gastric varices].

PMID- 8522088
TI  - [Endoscopic hemostasis of gastroduodenal ulcerous hemorrhages].

PMID- 8522089
TI  - [Indirect biological examinations in parasitic digestive pathology].

PMID- 8522090
TI  - [Hydatid cyst of the liver].

PMID- 8522091
TI  - [New parasitoses and news in parasitology].

PMID- 8522092
TI  - [Esophago-gastroduodenal involvement in human immunodeficiency virus infection].

PMID- 8522093
TI  - [Parasitic and viral enteritis in human immunodeficiency virus infection].

PMID- 8522094
TI  - [Diagnostic and therapeutic management of diarrhea in human immunodeficiency
      virus infected patients].

PMID- 8522095
TI  - [Proctology and human immunodeficiency virus].

PMID- 8522096
TI  - [Diagnostic and therapeutic strategy in severe acute colitis in adults].

PMID- 8522097
TI  - [Hepatobiliary and pancreatic diseases in human immunodeficiency virus
      infection].

PMID- 8522098
TI  - [Nutrition and human immunodeficiency virus infection].

PMID- 8522099
TI  - [Complications of digestive endoscopy].

PMID- 8522100
TI  - [Prognostic indices in acute pancreatitis. Practical implications].

PMID- 8522101
TI  - [Massive lower digestive hemorrhages. Diagnostic and therapeutic approach].

PMID- 8522102
TI  - [Mechanism of drug-induced hepatitis. A consequence of superposition of two
      xenobiotic systems].

PMID- 8522103
TI  - [Drug-induced acute hepatitis. Imputability and clinical aspects].

PMID- 8522104
TI  - [Chronic drug-induced hepatopathies. Imputability and clinical aspects].

PMID- 8522105
TI  - [Drug-induced acute pancreatitis].

PMID- 8522106
TI  - [Drug-induced enterocolitis (non-steroidal anti-inflammatory agents excluded)].

PMID- 8522107
TI  - [Intestinal complications induced by non-steroidal anti-steroidal anti
      inflammatory agents].

PMID- 8522108
TI  - [Intestinal immunology in digestive parasitoses].

PMID- 8522109
TI  - [Intestinal and hepatic amebiasis. Clinical and therapeutic aspects].

PMID- 8522110
TI  - [What do we expect from a parasitological examination of feces?].

PMID- 8522111
TI  - [Messenger RNA of duodenal cholecystokinin: thanks to endoscopy...].

PMID- 8522112
TI  - [Expression of the gene of cholecystokinin. Demonstration from duodenal biopsies
      in man].
AB  - Cholecystokinin (CCK) is a peptide released after feeding. Until now, CCK gene
      expression has been studied only on sacrified animals on mucosa scrapped off the
      duodenum. OBJECTIVE--The aim of this study was to assess CCK-mRNA detection on
      duodenal biopsy specimens in subjects undergoing gastrointestinal endoscopy.
      METHODS--Six biopsy specimens were taken from 6 healthy subjects, a) after a 12-h
      overnight fast and b) 6 or 12 h after a fat meal, and inducing a CCK release. CCK
      mRNA was analyzed by Northern blot. RESULTS--Plasma CCK levels increased from
      basal levels of 0.5 +/- 0.1 pmole/L to 8.2 +/- 1.5 pmole/L 10 min after the meal.
      The fasting CCK-mRNA levels were 44.0 +/- 0.6% and the post-prandial levels
      increased to 74.0 +/- 6.0% at 6 h and decreased to 47.5 +/- 0.5% at 12 h.
      CONCLUSIONS--Detection of CCK gene expression in human duodenal biopsy specimens
      is feasible. Stimulation of CCK release after a meal is followed by an increase
      in CCK-mRNA in the duodenal mucosa.

PMID- 8522113
TI  - [Effect of the duration of chronic alcoholic pancreatitis on the severity of
      outbreaks of acute pancreatitis].
AB  - OBJECTIVES: The aim of this study was to assess the severity of 66 bouts of acute
      pancreatitis according to CT scan classification in 52 patients with alcoholic
      chronic pancreatitis in relation with the duration of the disease. METHODS:
      Patients without pancreatic collection were classified as benign bouts, others as
      severe. RESULTS: Benign and severe acute pancreatitis occurred after a mean
      duration of 29.5 and 21.4 months, respectively (P < 0.05). Pancreatic
      calcifications were present on CT scan in 56% and 23% of the benign and severe
      groups, respectively (P = 0.008). No deaths occurred. CONCLUSION: The severity of
      acute bouts of pancreatitis decreases during chronic alcoholic pancreatitis
      course, particularly when pancreas is calcified.

PMID- 8522114
TI  - [Stimulation of adenylate cyclase by the isoforms of human and rat beta-3
      adrenergic receptor expressed in the CHO cells].
AB  - OBJECTIVES AND METHOD: The beta 3 adrenergic receptor stimulates lipolysis and
      colonic relaxation in the rat, and, suggestively, in man. Several human forms
      generated by different mRNA splicings can occur: the A form of 396 amino acids
      and the B and C forms extended by 12 and 6 amino acids respectively, in the C
      terminus region. In order to characterize these different forms as expressed in
      CHO cells, we studied adenylyl cyclase stimulation by the beta 3 agonists,
      SR58611A and BRL37344 and its inhibition by the beta 3 antagonist SR59230.
      RESULTS: This antagonist totally inhibited SR58611-adenylyl cyclase stimulation
      with the following hierarchy of potency: C form >> B > A. In rat, a unique form
      is expressed which is close to the human B form. This form was the less sensitive
      to beta 1 and beta 2 antagonists. CONCLUSION: These findings constitute a
      molecular pharmacological basis for the design of beta 3 agonists of therapeutic
      value.

PMID- 8522115
TI  - [The muscarinic system of the gastrointestinal smooth muscle].

PMID- 8522116
TI  - [Diversion colitis].

PMID- 8522117
TI  - [Hepatic puncture-biopsy of diffuse diseases of the liver: to see or not to
      see?].

PMID- 8522118
TI  - [Frequency and severity of viral hepatitis C after liver transplantation. Study
      in 28 patients].
AB  - OBJECTIVES AND METHODS: HCV cirrhosis is one of the major indications for liver
      transplantation. HCV recurrence rate is high but long term development to
      cirrhosis seems to be rare. This study included 28 patients with HCV infection
      (HCV RNA in blood, histologic lesions highly suggestive or compatible with HCV
      infection). RESULTS: Twenty-one out of the 28 patients were transplanted for
      hepatic chronic liver disease associated with HCV infection (reinfection),
      whereas only 7 out of 94 transplanted patients (7.4%) without pre-transplant HCV
      infection ("de novo" infection). Patients were followed clinically and
      histologically for a mean period of 26.8 months (range: 3-56). Of 26 patients
      with a good histological evaluation, 24 (92.3%) had chronic hepatitis: 7 with
      mild activity, 17 with moderate activity, 7 of whom had bridging fibrosis. Two
      patients had unusual features with associated lesions (necrotic hepatitis and
      chronic rejection in one case, acute hepatitis associated with CMV infection in
      the other). CONCLUSION: This study confirms the high prevalence of HCV
      recurrence, as well as the "de novo" infection risk, and suggests caution
      concerning long term prognosis.

PMID- 8522119
TI  - [Carbohydrate-deficient transferrin and liver diseases. Study of 94 patients].
AB  - OBJECTIVES AND METHODS: Carbohydrate-deficient transferrin has been proposed as a
      marker of alcohol consumption. The aim of this study was to evaluate the accuracy
      of the carbohydrate-deficient transferrin serum level, measured by ion exchange
      chromatography followed by radioimmunoassay (Kit CDTect), for the diagnosis of
      excessive alcohol intake in patients with liver diseases. Ninety-four patients
      (68 men, 26 women, age 21-71 years), 42 with alcoholic liver diseases and 52 with
      non-alcoholic liver diseases, were studied. Twenty-six patients consumed > or =
      40 g alcohol per day (mean alcohol intake: 84 +/- 52 g per day) and were
      considered to be excessive drinkers. RESULTS: The sensitivity of carbohydrate
      deficient transferrin for the diagnosis of excessive alcohol intake was 35%, and
      the specificity was 91%. By pairing carbohydrate-deficient transferrin with other
      markers of alcohol consumption, the sensitivity of the association of
      carbohydrate-deficient transferrin and gammaglutamyl transpeptidase was 96%, and
      the specificity was 59%. CONCLUSION: In patients with liver diseases,
      carbohydrate-deficient transferrin is a specific marker of excessive alcohol
      intake but a lack of sensitivity may limit its use.

PMID- 8522120
TI  - [Ultrasound-guided puncture-biopsy of the liver could replace blind puncture
      biopsy in diffuse hepatopathies. Retrospective study of 1293 patients].
AB  - OBJECTIVES: The aim of this retrospective study was to compare the efficiency and
      complications of percutaneous hepatic biopsy either guided by ultrasonography in
      the left lobe, or blindly by the intercostal route in the right lobe, in the
      diagnosis of diffuse liver diseases. PATIENTS AND METHODS: Liver biopsy was
      performed in 1,293 patients for 5 years. In group 1 (289 patients, including 140
      out-patients), liver biopsy was guided by ultrasound. In group 2, blind
      intercostal liver biopsy was performed in 1,004 patients. Patients were observed
      for 6 hours after biopsy in both groups. RESULTS: The failure rate of liver
      biopsy was significantly lower in group 1 (1.7%) than in group 2 (9.25%, P <
      0.01). The prevalence of the histological lesions was similar in both groups. No
      related-biopsy death occurred. Complications were more serious after blind biopsy
      (1 acute pancreatitis with a hematoma of the liver, 1 bile leakage around the
      gallbladder, 1 hemoperitonitis, 1 large intrahepatic hematoma), than after guided
      biopsy (1 small hematoma of the liver, 1 acute biliary pain on the 10th day).
      CONCLUSION: Hepatic biopsy guided by ultrasonography could replace blind biopsy
      in the diagnosis of diffuse liver diseases.

PMID- 8522121
TI  - [Indications and modalities of cholecystectomy in cholelithiasis. Study Group of
      Cholecystectomy, under the aegis of the National Agency for the Development of
      Medical Evaluation].

PMID- 8522122
TI  - [Isolated and spontaneously regressive colonic neurofibromatosis].
AB  - This case report concerns a man presenting protein losing enteropathy. Multiple
      polypoid colonic lesions were discovered corresponding to intra and submucosal
      neurofibromas. No extradigestive sign was noticed, and the diagnosis of isolated
      colonic neurofibromatosis was upheld. Eight years later, it was observed that
      both protein losing enteropathy and the colonic neurofibromas had apparently
      spontaneously disappeared. Isolated digestive neurofibromatosis and spontaneous
      tumoural regressions are discussed.

PMID- 8522123
TI  - [Ganglio-esophageal fistula revealed by hematemesis: a rare complication of
      silicotuberculosis].
AB  - We report a case of fistula between a silicotic mediastinal lymph node and the
      esophagus with protrusion of a stiff and darkish concretion into the oesophageal
      lumen. The patient, a 68-year-old coal miner, presented with cough since a few
      months and the lesion was revealed by haematemesis. The general course was
      rapidly favourable. Association with tuberculosis was recognized only a few
      months later.

PMID- 8522124
TI  - [Uterine metastasis revealing gastric adenocarcinoma].
AB  - We report a case of metastasis to the uterine corpus revealing a primary gastric
      adenocarcinoma. A 26-year-old woman suffered from weight loss, vaginal bleeding,
      abdominal pain. An endometrial curettage showed apparently metastatic
      adenocarcinoma. The primary site of the tumour was gastric. The upper
      gastrointestinal endoscopy revealed an ulcus and aspect of linitis plastica in
      the fundus. Biopsies showed diffuse type adenocarcinoma. Because of extensive
      disease, laparotomy was not performed and exclusive palliative chemotherapy was
      started. The patient died 10 months after the diagnosis. Metastasis from primary
      gastric cancer to the female genital tract are rare and are usually observed in
      young premenopausal women with diffuse type gastric adenocarcinoma. This case
      report underlines the interest, for those patients of careful gynaecologic
      examination at the initial staging and after treatment.

PMID- 8522125
TI  - [A new hereditary cause of portal vein thrombosis: the abnormal resistance to
      activated protein C by the Arg 506-->Gln mutation of the gene of factor V].
AB  - We report 2 cases of portal vein thrombosis associated with a single point
      mutation in the factor V gene that replaces arginine in residue 506 with
      glutamine. This mutation induces abnormal resistance to anticoagulant activity of
      activated protein C and increases the risk of deep vein thrombosis. Both patients
      had a personal and familial history of deep vein thrombosis. Intraabdominal
      neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome,
      paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency
      (antithrombin, proteins C and S) were excluded by exhaustive investigation.
      However, an abnormal resistance to activated protein C was found, and DNA
      analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant
      treatment was begun. A study of family history made in one case, showed the same
      genetic disease in one of the relatives. Resistance to activated protein C with
      factor V gene mutation should be investigated in patients with portal vein
      thrombosis. A study of family history, and anticoagulant treatment are justified
      for symptomatic patients.

PMID- 8522126
TI  - [Urinary ascites: response to the letter of J.-F. Blanc et al].

PMID- 8522127
TI  - [False pneumoperitoneum revealing Chilaiditi syndrome].

PMID- 8522128
TI  - [Ogilvie syndrome, complicating two cesarean sections, in a patient with normal
      digestive function. Probable role of a morphine-calcium inhibitor combination].

PMID- 8522129
TI  - [Computed tomography in the diagnosis of biliary ileus: a new case].

PMID- 8522130
TI  - [Severe liver cirrhosis and liver transplantation: original complication of
      reducing diets].

PMID- 8522131
TI  - [Significant increase of serum CA 19-9 antigen level in acute alcoholic
      hepatitis].

PMID- 8522132
TI  - [Autoimmune thrombocytopenic purpura after treatment of chronic viral hepatitis C
      with interferon].

PMID- 8522133
TI  - [Acute cytolytic hepatitis caused by cefazolin and metronidazole].

PMID- 8522134
TI  - [Crohn disease or hemorrhagic rectocolitis? CD 44V6 and CD 44V3 adhesion
      molecules can make the difference].

PMID- 8522135
TI  - The viable but non-culturable state in the human pathogen Vibrio vulnificus.
AB  - Vibrio vulnificus is a serious human pathogen, accounting for 95% of all seafood
      related deaths in the United States. During the winter months, when coastal water
      temperatures drop below 10 degrees C, investigators have repeatedly reported
      their inability to isolate this estuarine bacterium from the environment. We now
      realize that this apparent 'die-off' is actually due to entry of the cells into a
      'viable but non-culturable' state, a survival response to the low temperature
      stress. Cells in this state appear dormant, and cannot be cultured in or on
      routine bacteriological media, but are capable of returning to the actively
      metabolizing state when the environmental stress is removed. This review
      describes this non-culturable state in V. vulnificus, and its role in the
      ecology, physiology, and epidemiology of this pathogen.

PMID- 8522136
TI  - micF RNA is a substrate for RNase E.
AB  - Ribonuclease E (RNase E) is known to play an important role in mRNA decay and RNA
      processing in Escherichia coli. While several substrates for RNase E have been
      identified, the specificity for the recognition and cleavage sites has not been
      completely determined. In this study, micF RNA, an antisense RNA found in E. coli
      and related bacteria, was found to be a substrate for RNase E in vitro. Two
      cleavage sites were mapped, and both are found in the sequence context UA/UUU and
      are located within 10 nucleotides upstream of stem-loop structures. These results
      help define a generalized RNase E cleavage/recognition pattern.

PMID- 8522137
TI  - Gavaserin and saltavalin, new peptide antibiotics produced by Bacillus polymyxa.
AB  - A strain of Bacillus polymyxa (BPl), isolated from cauliflower seeds, inhibited
      the growth of microbial phytopathogens. Growth of this strain in liquid medium
      containing lactose, ammonium sulfate, biotin, and amino acids, resulted in
      optimal inhibition in vitro. Two new antibacterial substances were isolated and
      purified from culture broth. Their molecular masses were, respectively, 911 and
      903 daltons. The first compound was named gavaserin because it contained glutamic
      acid, alanine, valine, serine and 2,4-diaminobutyric acid, and octanoic acid. No
      fatty acid was detected in the second compound, which was named saltavalin
      because it contained serine, alanine, leucine, threonine, valine, and 2,4
      diaminobutyric acid.

PMID- 8522138
TI  - Identification of the genes in multicopy plasmids affecting ompC and ompF
      expression in Escherichia coli.
AB  - Osmoregulation of the porin genes, ompF and ompC of Escherichia coli, occurs at
      the level of transcription through the action of EnvZ and OmpR proteins as well
      as at the level of translation through micF antisense RNA. In this study, we used
      a genetic screening approach to identify new genes which interfere with the
      expression of ompC or ompF. Using an E. coli genomic library in pUC19, we
      identified three clones whose products altered expression of ompC and ompF in
      response to medium osmolarity. One clone carrying the secB gene was found to
      block ompC and inhibit ompF expression. One clone carrying gcvA, a
      transcriptional regulator for the gvcA operon, was found to block ompF expression
      at high osmolarity and elevate ompC expression at low osmolarity. One clone
      carrying rbsR, a repressor for the rbs operon, was found to block ompF expression
      at both low and high osmolarities and elevate ompC expression at low osmolarity.
      These results suggest that ompF and ompC expression is associated with other
      physiological regulating systems in addition to osmoregulation.

PMID- 8522139
TI  - Metabolism of phenols by Ochromonas danica.
AB  - This study investigated the catabolic potential of a eukaryotic alga to degrade
      one of the most common organic pollutants, phenol. The alga, Ochromonas danica
      (993/28), was selected for study after screening for its heterotrophic
      capabilities. The catabolic versatility of the alga was elucidated by incubating
      with a variety of phenolic compounds. The alga removed phenol, all the cresol
      isomers and 3,4-xylenol from its incubation media, with phenol being removed more
      rapidly than any of its methylated homologues. Consequently, the alga was found
      to have a greater specificity for phenol than for o- or p-cresols. This study
      shows that O. danica could catabolize phenol and its methylated homologues.

PMID- 8522140
TI  - Degradation of chlorobiphenyls catalyzed by the bph-encoded biphenyl-2,3
      dioxygenase and biphenyl-2,3-dihydrodiol-2,3-dehydrogenase of Pseudomonas sp.
      LB400.
AB  - In order to characterize the metabolites produced in vivo by biphenyl-2,3
      dioxygenase and biphenyl-2,3-dihydrodiol-2,3-dehydrogenase, the first two enzymes
      of the (polychloro)biphenyl catabolic pathway encoded by the bph locus of
      Pseudomonas sp. LB400, recombinant E. coli strains expressing the respective
      genes were constructed. Biphenyl-2,3-dioxygenase attack on 2,2'- or 2,4'
      dichlorobiphenyl was shown to give rise to virtually quantitative ortho
      dechlorination of these congeners by hydroxylation at the chlorinated carbon 2
      and its unsubstituted neighbour. Elimination of hydrochloric acid directly leads
      to 2,3-dihydroxy-chlorobiphenyls and obviates the need for biphenyl-2,3
      dihydrodiol-2,3-dehydrogenase for the catabolism of such congeners.

PMID- 8522141
TI  - Rapid detection and identification of odontoglossum ringspot virus by polymerase
      chain reaction amplification.
AB  - The odontoglossum ringspot Tobamovirus (ORSV) movement and coat proteins genes
      were selected for the design of oligonucleotide primers for amplification of a
      1,085 bp fragment. A combined assay of reverse transcription and the polymerase
      chain reaction (RT-PCR) was performed with 20-mer ORSV-specific primers and crude
      nucleic acid extracts from virus-infected orchids for rapid detection of the
      virus. The lowest concentration of template viral RNA required for detection was
      10 fg. The RT-PCR is a 10(3) times more sensitive, reproducible and time-saving
      method than the enzyme-linked immunosorbent assay. No PCR product was observed
      when cymbidium mosaic potexvirus or a crude extract of healthy Cymbidium sp. were
      used as a template in RT-PCR with the same primers. The specificity of the
      primers was verified using other tobamoviruses RNAs.

PMID- 8522142
TI  - Cellular location influences copper-dependent topaquinone formation for
      phenylethylamine oxidase expressed in Escherichia coli K-12.
AB  - Arthrobacter globiformis amine oxidase produced by Escherichia coli cells grown
      in copper-depleted media was reported to undergo activation due to formation of
      its topaquinone cofactor in a copper-dependent autocatalytic reaction. Likewise,
      a mutated E. coli amine oxidase located in the cytoplasm was reported to form
      topaquinone autocatalytically in an EDTA-sensitive reaction. Here we show
      unequivocally that formation of an amine oxidase lacking topaquinone is primarily
      a consequence of the location of the enzyme in the cytoplasm rather than the
      level of copper in the growth medium. For E. coli, insertion of copper into
      apoamine oxidase and subsequent topaquinone formation occur after export of the
      apoenzyme into the periplasm.

PMID- 8522143
TI  - Identification of a 13-kDa protein associated with the polyhydroxyalkanoic acid
      granules from Acinetobacter spp.
AB  - Proteins associated with poly-beta-hydroxybutyrate (PHB) granules were purified
      from four Acinetobacter strains isolated from modified activated sludge treatment
      plants. Four predominant proteins of 64 kDa, 41 kDa, 38 kDa and 13 kDa were
      identified. N-terminal amino acid sequencing of the 64-kDa and 13-kDa proteins
      from Acinetobacter RA3849 identified these proteins as the products of the phaCAc
      and phaPAc (formerly designated ORF1) genes, respectively. The expression of the
      13-kDa protein (referred to as GA13) is shown to be required for the accumulation
      of large amounts of PHB in a recombinant Escherichia coli strain.

PMID- 8522144
TI  - The Rhizobium meliloti region located downstream of the nod box n6 is involved in
      the specific nodulation of Medicago lupulina.
AB  - Six nod box regulatory sequences are present in the Rhizobium meliloti genome. We
      have analysed the DNA region located downstream of nod box n6, and identified
      three open reading frames, designated nolQa, nolQb and nolS. LacZ fusions in
      these ORFs are not induced by classical nod gene inducers, which indicates that
      their expression either is not under the control of the nod box, or involves
      another regulatory mechanism acting in conjunction with the NodD/nod box
      regulatory circuit. Mutations in this n6 locus result in a delay in nodule
      formation on a particular host, Medicago lupulina. As this region is not strictly
      conserved among different R. meliloti strains, nolQa, nolQb and nolS may
      constitute auxiliary nodulation genes, for which the selection pressure is
      limited to particular host plants.

PMID- 8522145
TI  - Medical and depressive comorbidity in psychiatric inpatients.

PMID- 8522146
TI  - DSM-IV primary care version: an opportunity for general hospital and consultation
      liaison psychiatrists?

PMID- 8522147
TI  - Impact of the interaction of depression and physical illness on a psychiatric
      unit's length of stay.
AB  - Prior literature suggests that length of stay (LOS) on medical inpatient units is
      increased by the coexistence of depression and physical illness. The present
      study examined 532 psychiatric inpatient admissions to determine if physical
      illness increased LOS for patients grouped by diagnostic categories of psychosis,
      depression, personality disorder, anxiety disorder, adjustment disorder, bipolar
      disorder (not depressed), and other psychiatric disorders. LOS for depressed
      patients was significantly longer for those with any physical final diagnosis
      (mean = 20.08 days) than for depressed patients with no physical diagnosis (mean
      = 11.48 days). LOS was also longer for all patients with physical diagnoses (mean
      = 19.31 days) than all patients with no physical diagnosis (mean = 13.13 days).
      No other specific diagnostic group (psychosis, personality disorder, and so
      forth) showed significant differences in LOS for any associated physical illness
      vs no physical illness. The study results tend to indicate that physical illness
      is associated with increased LOS for depressed psychiatric patients but not for
      other specific diagnostic groups. Depressed patients may 1) mask physical illness
      by depression-generated physical complaints; 2) prioritize mood symptoms over
      physical symptoms; and/or 3) may suffer from feelings of hopelessness or be
      pessimistic that their physical symptoms will be effectively treated and,
      therefore, not report their physical symptoms.

PMID- 8522148
TI  - Treatment of delayed sleep phase syndrome.
AB  - Delayed sleep phase syndrome (DSPS) is a common but little reported cause of
      severe insomnia. Affected individuals complain of difficulty falling asleep and
      difficulty awaking at socially acceptable hours. It results from a dysregulation
      of the circadian sleep-wake cycle. DSPS presents in clinically heterogenous ways
      as modulated by motivation, psychopathology, drug status, and treatment
      compliance factors. Patients respond variably to the range of possible
      treatments. Bright light treatment potentially corrects the circadian abnormality
      of DSPS. Other treatments reported to relieve some DSPS patients include schedule
      shifts, drugs, and vitamin and hormone treatments. The safety and efficacy of
      light treatment have not been conventionally defined, but available information
      suggests that it is ophthalmologically safe. At present, DSPS must be managed
      empirically by various methods.

PMID- 8522149
TI  - An assessment of rates of psychiatric morbidity and functioning in HIV disease.
AB  - This study examined demography, rates of psychopathology, and functional
      impairment in HIV-seropositive women and men in a large, urban, public outpatient
      infectious disease clinic. Fifty-three percent of the women and 70% of the men
      met Structural Clinical Interview for DSM-III-R criteria for psychiatric
      disorders. Current mood disorders were the most frequent diagnoses, followed by
      psychoactive substance abuse/dependence disorders and psychotic disorders.
      Seventy-six percent of the women and 90% of the men had previous psychiatric
      histories, including 59% of the women and 55% of the men who had psychiatric
      histories prior to their knowledge of HIV seroconversion. Depressed subjects
      reported significant impairment in physical, social, and role functioning.
      Similarly, impairment in physical functioning was highly correlated with self
      reported anxiety symptoms. These data suggest considerable past and current
      psychiatric comorbidity in HIV-infected individuals seeking medical care, and
      draw attention to the need for recognition and aggressive psychiatric treatment,
      particularly for those depressed and anxious patients with impaired functioning.

PMID- 8522150
TI  - Differential diagnosis and treatment of steroid-induced affective syndromes.
AB  - The differential diagnosis of hypercortisolemia is complex, particularly when the
      clinician must distinguish Cushing's syndrome (CS) from major depression. The
      present clinical case history demonstrates that by means of physical and
      laboratory examinations, the psychiatrist can make the initial differentiation,
      in consultation with medical specialists. The use of the corticotropin-releasing
      factor (CRF) stimulation test may be especially helpful in distinguishing
      Cushing's disease (CD) from major depression, though there is some degree of
      "overlap" in results. This suggests that these disorders may lie along a
      continuum of hypothalamopituitary dysfunction.

PMID- 8522151
TI  - Coping and the decision to hospitalize in emergency psychiatry.
AB  - This study was done to clarify whether and in what way a patient's coping
      repertoire can be linked to the disposition decision in a psychiatric emergency
      service. For 1 year, all consultations (N = 1439) of a psychiatric emergency
      service were documented in a detailed questionnaire covering sociodemographic and
      diagnostic data as well as information about the disposition decision. Depending
      on disposition, three groups were identified: outpatients (N = 530), inpatients
      (N = 481), and a nonintervention group (N = 428). In addition, over a 5-month
      period, patients were requested to fill in the "Bernese Coping Modes"
      questionnaire. Thus, a sample of 28 patients undergoing outpatient crisis
      intervention and 28 patients referred to inpatient treatment was obtained.
      Statistical analysis included Chi square-test, t-test, Mann-Whitney U-test, and
      logistic regression analysis. Assessment of coping repertoire contributed more
      than the diagnosis to the decision to hospitalize. Outpatients have a larger
      coping repertoire (t = 3.48, p = 0.001) than inpatients and show higher values in
      "acceptance-stoicism," "dissimulation," "tackling," "giving meaning," "altruism,"
      "optimism," and "relativizing." Logistic regression revealed relativizing,
      altruism, and optimism as being most important. Self-referral to emergency
      psychiatry was also correlated with outpatient treatment. Other criteria such as
      being without work, living alone, history of previous hospitalization, and the
      diagnosis of a psychotic or mood disorder were significantly correlated with
      referral to inpatient treatment. More attention should be paid to patients'
      coping repertoires in emergency services when deciding about the need for
      inpatient treatment.

PMID- 8522152
TI  - Delirium in critical care unit patients admitted through an emergency room.
AB  - Two hundred thirty-eight patients admitted consecutively to a critical care unit
      through an emergency room were assessed prospectively for the presence of
      delirium. Thirty-eight patients (16%) developed delirium. Delirium occurred with
      equal frequency in all disease categories. The presence of abnormal head imaging
      which required medical intervention did not predict the development of delirium.
      The median delay between admission and the development of delirious was 4 days,
      however, one-fourth of the patients were delirious on the day of admission. The
      patients with abnormal head imaging who required medical intervention had a
      higher frequency of onset of delirium on the first day compared with patients
      without. The delirium lasted a median of 5 days and resolved within a week in
      over 70% of patients. These results confirm that delirium is frequently present
      in patients who require acute critical care after emergency room evaluation. In
      this population, serious medical disease is a better predictor of the development
      of delirium than the presence of abnormal brain imaging which required medical
      intervention. Although delirious patients have longer lengths of stay, the
      presence of delirium does not predict higher mortality, as has been reported in
      other populations. This could be because delirious patients admitted to the
      critical care unit through the emergency room have fewer premorbid medical
      problems predisposing them to poor outcome.

PMID- 8522153
TI  - Does physical improvement reduce depressive symptoms in HIV-infected medical
      inpatients?
AB  - The Beck Depression Inventory, Karnofsky Scale of Physical Performance, and a
      visual-analogue scale to assess subjective distress were administered to 32 HIV
      infected medical inpatients shortly after admission and prior to discharge.
      Twenty-eight percent of subjects had severe depressive symptoms on admission.
      Most of these subjects remained in the severe range of depressive symptoms at
      discharge, despite physical improvement comparable to subjects with lower levels
      of depressive symptoms. In contrast, subjects with moderate depressive symptoms
      on admission showed a significant decrease in depressive symptoms at discharge.
      The results suggest that the etiology and management of depressive symptoms in
      HIV-infected medical inpatients may differ depending on the initial severity of
      depressive symptoms.

PMID- 8522154
TI  - Burning mouth syndrome. Successful treatment with combined psychotherapy and
      psychopharmacotherapy.
AB  - A case is presented that illustrates the possible role of significant life events
      and depression in the etiology of the burning mouth syndrome. Furthermore,
      successful treatment with a combination of a selective serotonin re-uptake
      blocking antidepressant (sertraline) and psychodynamically oriented psychotherapy
      is described.

PMID- 8522155
TI  - Migraine with aura and functional psychosis: a rare differential diagnosis.

PMID- 8522156
TI  - Commensalism, adaptation and gene flow: mosquitoes of the Culex pipiens complex
      in different habitats.
AB  - Two ecotypes have been described for Culex pipiens mosquitoes of the temperate
      zone: a human commensal type and a feral type, but their degree of evolutionary
      differentiation and taxonomic status are still unclear. The commensal form is
      characterized by life-history traits probably adaptive to underground man-made
      environments. This situation has sometimes been considered as an example of
      recent speciation although the existence of intermediate forms indicates that the
      balance between gene flow and disruptive selection should first be assessed. The
      present study was concerned with (1) the determination of biological traits
      involved in adaptation to commensalism, and (2) the pattern of gene flow within
      and between ecotypes in a restricted area. It was found that (1) significant
      differences in biological traits exist between mosquitoes from different
      habitats, (2) characteristics of the commensal type are not universal in
      mosquitoes from underground man-made habitats, (3) allozyme markers do not
      clearly differentiate ecotypes and (4) insecticide resistance genes, which reveal
      recent migration, occur in each ecotype. These results are discussed in the
      context of possible speciation due to commensalism.

PMID- 8522157
TI  - The distribution of transposable elements on X chromosomes from a natural
      population of Drosophila simulans.
AB  - The distribution of 13 transposable element families along 15 X chromosomes from
      an African natural population of Drosophila simulans was determined by in situ
      hybridization to polytene chromosomes. The transposable elements cloned from
      Drosophila melanogaster all hybridized with Drosophila simulans chromosomes. The
      number of copies per family was 3.5 times lower in the latter species and
      correlated with the copy number per family in Drosophila melanogaster. With the
      exception of 297, the copy number per chromosome followed a Poisson distribution.
      Element frequencies per chromosome band were generally low. However, several
      sites of the distal region and the base of the X chromosome had high frequencies
      of occupation. Elements had higher abundance at the base of the chromosome
      compared to distal regions. Overall, the distribution of transposable elements in
      Drosophila simulans is similar to that found in Drosophila melanogaster. These
      data provide evidence for the operation of a force (or forces) opposing
      transpositional increase in copy number, and that this force is weaker at the
      bases of chromosomes, consistent with the idea that recombination between
      elements at non-homologous sites contains TE copy number. The reduction in copy
      number of all TE families in Drosophila simulans compared to Drosophila
      melanogaster can be explained by stronger selection against transposable element
      multiplication and/or lower rates of transposition in Drosophila simulans.

PMID- 8522158
TI  - The genetics of tasting in mice. VII. Glycine revisited, and the chromosomal
      location of Sac and Soa.
AB  - Previous work which appeared to show that some strains of mice taste glycine
      solutions as bitter has been found to be in error. The bitterness came from
      copper glycinate which formed in the brass drinking spouts. Taste testing with
      copper glycinate shows that the genetical data identifying the gene Glb are still
      valid. The close linkage of Glb and Rua has been confirmed. Most strains of mice
      prefer glycine solution to water, presumably because the glycine tastes sweet.
      The degree of preference for glycine is correlated with the degree of preference
      for other sweet substances such as saccharin or acesulfame. The gene dpa appears
      not to be involved. The sweetness tasting gene Sac has been mapped to chromosome
      4 at 8.1 +/- 3.4 cM distal to Nppa (formerly Pnd). The bitterness tasting gene
      Soa is very closely linked to Prp on chromosome 6 (no recombinants among 67
      backcross progeny). It is suggested that the sweetness and bitterness tasting
      genes have descended from a common ancestral tasting gene which existed before
      the tetraploidization of the genome which took place in early vertebrate
      evolution.

PMID- 8522159
TI  - Chloride channel 2 gene (Clc2) maps to chromosome 16 of the mouse, extending a
      region of conserved synteny with human chromosome 3q.
AB  - The Clc2 gene of the mouse codes for the ubiquitously expressed chloride channel
      ClC-2, a member of a family of at least seven voltage gated chloride channels,
      some of which are implicated in hereditary diseases. Using a mouse interspecies
      back-cross panel, we have mapped Clc2 to Chr 16, proximal to the somatostatin
      gene Smst, extending a region of documented conserved synteny to human Chr 3q.

PMID- 8522160
TI  - Density and age-specific mortality.
AB  - Age-specific mortality rates decelerate at older ages in laboratory populations
      in the Medfly Ceratitis capitata. This has been interpreted by Carey et al.
      (1992) to reflect a slowing of the aging process, but might also be explained by
      declining adult density. Here it is argued that the density explanation, as
      presented by Graves and Mueller (1993), is unpersuasive for several reasons:
      extrapolations from Drosophila to Medflies are unjustified; the range of
      densities they studied is 2-120 times higher than that used in other studies;
      they ignore data on Medflies held in isolation, which rule out density effects;
      their own data suggest that initial cohort density has no effect on mortality
      rates at older ages, which is the relevant part of the life cycle; their
      experiment is too small to provide accurate estimates of mortality; new Medfly
      experiments executed at multiple densities show decelerating and then declining
      mortality rates at advanced ages for all densities. When Drosophila survivorship
      experiments are done on a sufficiently large scale they also show a deceleration
      of mortality at older ages that is not attributable to density effects. The
      deceleration of mortality rates is most likely a real facet of aging, and will
      have to be taken into consideration in any synthesis of the genetics and
      evolution of aging.

PMID- 8522161
TI  - Genetic characterization of geographic populations using morphometrical traits in
      Drosophila melanogaster: isogroups versus isofemale lines.
AB  - Studies of short or medium range geographic variations play an increasing role in
      ecological genetics, and sensitive techniques are required to detect them. In
      this respect, two sampling techniques were compared in D. melanogaster. The
      biological data were provided by the analysis of four natural populations from
      the same geographic area, Spain (one) and Southern France (three), for four
      morphometrical traits: abdomen and thoracic pigmentation, and wing and thorax
      lengths. Traits were measured on wild living females and on their progeny reared
      in the laboratory at 25 degrees C. For progeny analyses, two techniques were
      compared: the usual isofemale line technique, sib families issued from a single
      female, and a new isogroup technique, the progeny produced by a group of 20 wild
      collected parents. Large phenotypic variations were observed in wild living
      flies, corresponding to the unstability of natural environmental conditions
      during their development. Among laboratory grown flies, variations were much
      smaller. Between isogroups, differences were small, due to sampling error and
      some common environment effects. Variations between lines were much greater, thus
      demonstrating a strong genetic component. When different populations have to be
      compared, the isogroup technique should be preferred since, for the same amount
      of work, the lesser variability between groups provides a more precise
      characterization of the population means.

PMID- 8522162
TI  - Probing the evolution of senescence in Drosophila melanogaster with P-element
      tagging.
AB  - Natural populations host a wealth of genetic variation in longevity and age
      specific schedules of reproduction. This variation provides critical information
      for inferring the evolutionary origin of senescence. Patterns of mutational
      effects on age-specific fecundity and survival provide additional insight to
      distinguish alternative models of senescence. In this study, P-elements bearing
      the white minigene were inserted at random into a common genetic background,
      generating lines of D. melanogaster with single, stable transposon inserts. A
      series of 48 single-P-element lines revealed statistically significant
      heterogeneity in both longevity and fecundity. Longevity and early fecundity were
      only weakly positively correlated (r = 0.286, P = 0.0398). Both the pooled sample
      and 30 of the individual lines exhibited a leveling of age-specific mortality at
      advanced ages, in opposition to the classical demographic models. To the extent
      that these mutational effects are representative of naturally-occurring mutations
      in heterogeneous populations, this result presents a problem for the evolutionary
      theory of senescence. Natural selection is inefficient at removing deleterious
      mutations that are expressed only at late ages, and selection may not
      differentiate between mutations whose effects on longevity are post-reproductive.
      A leveling of the mortality rate would also be seen if mutations whose expression
      is delayed until very late simply do not occur. A simulation of mutation
      selection balance among the 48 P-element tagged lines shows that the mean
      longevity declines monotonically with increasing mutation rate, consistent with
      the mutation-accumulation model.

PMID- 8522163
TI  - Differential digestion of the centromeric heterochromatic regions of the 5
      azacytidine-decondensed human chromosomes 1, 9, 15, and 16 by NdeII and Sau3AI
      restriction endonucleases.
AB  - A study on the factors involved in chromosome digestion by restriction
      endonuclease was carried out on 5-azacytidine treated and untreated human
      chromosomes 1, 9, 15 and 16 by using NdeII and Sau3AI isoschizomers. After
      treatment with 5-azacytidine, chromosomes 1, 9, 15, and 16 showed two
      differentiated areas at the centromeric regions: the centromere, fully condensed,
      and the pericentromeric heterochromatin, decondensed. Chromosomes not treated
      with 5-azacytidine after digestion with Sau3AI and NdeII showed all the
      centromeric regions undigested, except pair number 1, digested at the
      pericentromeric area. Digestion of the 5-azacytidine decondensed chromosomes with
      Sau3AI and NdeII showed the centromeres undigested in the four chromosome pairs
      while the pericentromeric heterochromatin appeared largely digested. Other
      factors, different to target distribution, are necessary to explain the pattern
      of restriction endonuclease digestion observed in this communication.

PMID- 8522164
TI  - Adolescent idiopathic scoliosis as developmental instability.
AB  - Adolescent idiopathic scoliosis is the most common spinal deformity affecting
      children, with a prevalence from mass screening programmes of 1-3%. Despite
      centuries of study, it remains a problem with no generally accepted theory of
      aetiology, and disagreement on its natural history and management. Because the
      deformity consists ultimately of gross left-right asymmetry, a study was
      undertaken to test the hypothesis that it might be a manifestation of
      developmental instability. Palmar dermatoglyphics in 112 normal subjects, 62 with
      non-scoliosis trunk asymmetry and 85 with defined adolescent idiopathic scoliosis
      were examined and both the absolute right-left difference and the ratio of this
      to the total were considered. There was increased fluctuating asymmetry of atd
      difference in those with any asymmetry, scoliotic or not, and increased
      directional asymmetry of ab and cd ridge counts only in those with pure
      scoliosis. This suggests that, at adolescence, developmental instability may
      result in a loss of symmetry in growth, and that in the presence of an increased
      developmental left-right gradient, this may be of sufficient severity to be
      classified as deformity and come to the attention of orthopaedic surgeons. This
      interpretation changes the focus of many previous observations on scoliosis and
      raises the prospect that developmental stability in humans has relevance to
      problems hitherto restricted to clinical practice.

PMID- 8522165
TI  - Enzyme polymorphism in Drosophila melanogaster populations collected in two
      different habitats in Hungary.
AB  - The level of enzyme polymorphism was compared in ten Drosophila melanogaster
      populations collected in farmyards and distilleries in two regions of Hungary.
      The total genetic diversity was partitioned into between- and within-population
      components at each investigated locus using Wright's F-statistics. Population
      differentiation was studied in two different ways. Genetic distances between
      pairs of populations were calculated and a hierarchical analysis of gene
      diversity was performed. Based on the F values gene flow was estimated among the
      populations at different levels of the hierarchy. The results indicated that our
      'farmyard populations' collected within a region could be considered as parallel
      samples from a panmictic population rather than samples of distinct populations.
      In distilleries, the flies might be influenced by two different evolutionary
      forces: (i) selection due to the extremely high concentration of ethanol in the
      fermenting mash and (ii) genetic drift due to the combination of repeated founder
      effects and fluctuating population size. Our results suggested that 'distillery
      populations' could not be regarded as real populations either. They could be
      considered as peculiar cases: founder individuals taken from the total population
      (region) established special populations which survived in the distilleries for
      many generations. Thus the dominating force acting on the 'distillery
      populations' was genetic drift.

PMID- 8522166
TI  - The distribution of the transposable element Bari-1 in the Drosophila
      melanogaster and Drosophila simulans genomes.
AB  - The distribution of the transposable element Bari-1 in D. melanogaster and D.
      simulans was examined by Southern blot analysis and by in situ hybridization in a
      large number of strains of different geographical origins and established at
      different times. Bari-1 copies mostly homogeneous in size and physical map are
      detected in all strains tested. Both in D. melanogaster and in D. simulans a
      relatively high level of intraspecific insertion site polymorphism is detectable,
      suggesting that in both species Bari-1 is or has been actively transposing. The
      main difference between the two sibling species is the presence of a large tandem
      array of the element in a well-defined heterochromatic location of the D.
      melanogaster genome, whereas such a cluster is absent in D. simulans. The
      presence of Bari-1 elements with apparently identical physical maps in all D.
      melanogaster and D. simulans strains examined suggests that Bari-1 is not a
      recent introduction in the genome of the melanogaster complex. Structural
      analysis reveals unusual features that distinguish it from other inverted repeat
      transposons, whereas many aspects are similar to the widely distributed Tc1
      element of C. elegans.

PMID- 8522167
TI  - An adaptive chromosomal polymorphism affecting size-related traits, and longevity
      selection in a natural population of Drosophila buzzatii.
AB  - Size-related phenotypic variation among second-chromosome karyotypes in
      Drosophila buzzatii was examined in an Argentinian natural population. For all
      measured traits (thorax and wing length; wing, head and face width), this
      inversion polymorphism exhibited a significant and (additive) linear contribution
      to the phenotypic variance in newly emerged wild flies. The results suggest that
      only overall body size, and not body shape, is affected, as no karyotypic
      variation was found for any trait when the effects of differences in within
      karyotype size were removed with Burnaby's method. Likewise, in an experiment of
      longevity selection in the wild, variation in chromosomal frequencies was
      verified in the direction predicted on the basis of: (i) previous studies on
      longevity selection for body size in the wild and (ii) the pattern of chromosomal
      effects we observed on size. The direction of such selection is consistent with a
      pattern of antagonistic selection detected in previous studies on the inversion
      polymorphism.

PMID- 8522168
TI  - Sequence evolution of the Gpdh gene in the Drosophila virilis species group.
AB  - The nucleotide sequence of the Gpdh gene from six taxa, D. virilis, D. lummei, D.
      novamexicana, D. a. americana, D. a. texana and D. ezoana, belonging to the
      virilis species group was determined to examine details of evolutionary change in
      the structure of the Gpdh gene. The Gpdh gene is comprised of one 5' non
      translated region, eight exons, seven introns and three 3' non-translated
      regions. Exon/intron organization was identical in all the species examined, but
      different from that of mammals. Interspecific nucleotide divergence in the entire
      Gpdh gene followed the common pattern: it was low in the exon, high in the intron
      and intermediate in the non-translated regions. The degree of nucleotide
      divergence differed within these regions, suggesting that selection exerts
      constraints differentially on nucleotide change of the Gpdh gene. A phylogenetic
      tree of the virilis phylad constructed from nucleotide variation of total
      sequence was consistent with those obtained from other data.

PMID- 8522169
TI  - Geographic differentiation in wing shape in Drosophila melanogaster.
AB  - Genetic variation of a suite of 12 morphometric wing characters was examined in
      16 natural populations of Drosophila melanogaster from Eastern Europe and Central
      Asia using principal component analysis. The posterior wing compartment was found
      to differ in shape between the Eastern European and Central Asian populations.
      This result in agreement with data on wing shape variation from exposure to high
      and low temperatures under laboratory conditions.

PMID- 8522170
TI  - Construction of a cDNA library for a specific region of a chromosome using a
      novel cDNA selection method utilizing latex particles.
AB  - A novel method is described for the rapid concentration of particular cDNAs and
      their mapping to specific regions of a genome. The strategy for 'cDNA scanning'
      is based on the hybridization of an entire library of cDNAs to a large fragment
      of genomic DNA that is covalently bound to latex particles. The hybridized cDNAs
      are eluted, amplified by PCR and cloned into a lambda vector. Selected cDNAs that
      hybridized to the genomic DNA are cloned, with subsequent sequence analysis.
      Region-specific DNA fragments prepared from a yeast artificial chromosome (YAC)
      clone, EG10D9, which maps to chromosome 5 of the small cruciferous plant
      Arabidopsis thaliana (At), were used to prepare a model system and were
      covalently bound to latex particles. cDNAs that hybridized to EG10D9 were
      concentrated by hybridization to the immobilized DNA. The hybridized cDNAs were
      recovered and amplified by PCR. The resultant sub-library of cDNAs of 0.5-2 kb in
      length was enriched about 1000-fold. The partial sequences of the cDNAs provided
      information about genes that are located on the EG10D9 region of the At genome.
      The cDNA scanning strategy provides an efficient method for the mapping of
      expressed genes which could be used as expressed sequence tags (EST) within a
      genome.

PMID- 8522171
TI  - Characterization of an internal permissive site in the cholera toxin B-subunit
      and insertion of epitopes from human immunodeficiency virus-1, hepatitis B virus
      and enterotoxigenic Escherichia coli.
AB  - We previously described the construction of novel hybrid proteins based on the B
      subunit of cholera toxin (CTB) [Backstrom et al., Gene 149 (1994) 211-217], in
      which a neutralizing B-cell epitope from the third variable (V3) loop in the
      envelope glycoprotein gp120 from human immunodeficiency virus type 1 (HIV-1) was
      inserted within a surface-exposed region between amino acids (aa) 55 and 64. The
      resulting protein retained properties of native CTB and could induce strong anti
      CTB antibody (Ab) responses, but the inserted gp120 epitope was only modestly
      immunogenic. In this study, the potential use of this internal permissive site in
      CTB for the insertion of heterologous epitopes has been further investigated. Six
      additional plasmids were constructed encoding HIV::CTB hybrid proteins with ten
      to fourteen aa from the V3 loop of gp120 genetically inserted at different
      positions between aa 52 and 65, with deletions of different CTB aa. Plasmids
      encoding proteins with peptides inserted between aa 53 and 64 in CTB gave rise to
      stable proteins which reacted with CTB-specific monoclonal antibodies (mAb) and
      bound to GM1 gangliosides (GM1), indicating that insertions between these
      positions do not drastically alter the conformation or the receptor-binding
      properties of native CTB. Plasmids were also constructed encoding CTB hybrid
      proteins which had either an 11-aa peptide from hepatitis B virus (HBV) pre-S(2)
      or one of two peptides related to the heat-stable toxin (STa) of enterotoxigenic
      Escherichia coli inserted between aa 55 and 64 of CTB. This resulted in the
      production of HBV::CTB or ST::CTB hybrid proteins and illustrated that the
      internal permissive site can be used for insertion of peptides of varying aa
      composition. The reactivity of the inserted epitopes with epitope-specific mAb in
      GM1-ELISA and immunoblots varied greatly between hybrid proteins and depended on
      the position in CTB and the aa composition of the inserted peptides. Despite
      these differences, all the HIV::CTB, ST::CTB and HBV::CTB hybrid proteins could
      induce low, but significant, levels of serum Ab in mice against gp120, STa or pre
      S(2), in addition to strong serum Ab responses against CTB. The Ab response
      against the internally inserted gp120 peptide was similar to that against the
      same peptide fused to the N-terminus of CTB, indicating that internally placed
      peptides had similar immunogenicity to the same peptides added terminally.

PMID- 8522172
TI  - End joining of genomic DNA and transgene DNA in fertilized mouse eggs.
AB  - A linear 5.2-kb HS2/beta-globin construct with an upstream KpnI terminus (4
      nucleotide (nt) 3' protruding single strand, PSS) and a downstream SalI terminus
      (4-nt 5' PSS) was microinjected into fertilized mouse eggs. The injected DNA
      fragments integrated into the mouse genome primarily as a head-to-tail tandem
      array. Chromosome/transgene junctions were obtained from seven of eight
      transgenic animals. All of the junctions occurred in the proximity of a transgene
      KpnI end; a maximum loss of 8 nt from the transgene terminus was observed. Two of
      these junctions completely preserved the 4-nt KpnI 3' PSS. Transgene/transgene
      junctions from two animals were analyzed. SalI/KpnI junctions that completely
      preserved both the SalI 5' PSS and the KpnI 3' PSS were found in each animal.
      These are the first examples of complete nt preservation at junctions formed
      between a 5' PSS terminus and a 3' PSS terminus in transgenic mice. The data are
      consistent with the fill-in model of Thode et al. [Cell 60 (1990) 921-928] in
      which alignment proteins juxtapose 5' PSS and 3' PSS termini; DNA polymerase then
      utilizes the recessed 3'-OH of the 5' PSS terminus as a primer to synthesize DNA
      across the gap. This mechanism results in the formation of junctions with no loss
      of sequence. The results described in the present paper suggest that this
      mechanism may be involved in the formation of junctions in transgenic mice.

PMID- 8522173
TI  - A role for phosphorylation in the proteolytic processing of the human NF-kappa B1
      precursor.
AB  - A precursor, p105, for one of the subunits (p50) of the NF-kappa B transcription
      factor, plays an important role in inducible expression of diverse cellular
      genes. p105 also functions as a cytoplasmic inhibitor for NF-kappa B, and the
      proteolytic processing of its inhibitory C-terminal region is required for
      generation of active NF-kappa B. Here, it is reported that the human p105 C
      terminal region is phosphorylated in vivo on Ser894 and Ser908, which are
      potential phosphorylation sites in vitro for proline-directed serine/threonine
      kinases such as cyclin-dependent kinase. Furthermore, the mutation of these in
      vivo phosphorylation sites retards p105 processing in vivo, suggesting that p105
      processing is regulated in a phosphorylation-dependent manner.

PMID- 8522174
TI  - PCR haplotypes for the human Y chromosome based on alphoid satellite DNA variants
      and heteroduplex analysis.
AB  - We have developed a system for revealing informative and useful haplotypes for
      the human Y chromosome using PCR. Variant alphoid satellite DNA subunits were
      amplified and analysed by digestion with HindIII to score a restriction site
      polymorphism, or on polyacrylamide gels to reveal 13 heteroduplex haplotypes.
      Heteroduplexes are double-stranded DNA molecules containing mismatches; the
      haplotype is the combination of alleles on the same chromosome. Structural
      studies showed that the heteroduplexes analysed here were formed from loci at the
      left (short arm) and right (long arm) edges of the centromeric alphoid array
      which differed by a 4-bp insertion/deletion and several point mutations.
      Consequently, many haplotypes may have arisen only once and are useful for
      evolutionary studies.

PMID- 8522175
TI  - The yeast EGD2 gene encodes a homologue of the alpha NAC subunit of the human
      nascent-polypeptide-associated complex.
AB  - Two Saccharomyces cerevisiae proteins of 21 and 27 kDa co-purify with a novel
      enhancer of Gal4p DNA binding activity (Egdp) [Parthun et al., Mol. Cell. Biol.
      12 (1992) 5683-5689]. Mutations in the EGD1 gene encoding the 21-kDa protein
      (Egd1p) have been shown to affect the kinetics and extent of the Gal4p-mediated,
      galactose-induced activation of the GAL genes. Egd1p is homologous to human
      BTF3b, recently identified as the beta subunit of the heterodimeric nascent
      polypeptide-associated complex (NAC) involved in ensuring signal-sequence
      specific protein sorting and translocation [Wiedmann et al., Nature 370 (1994)
      434-440]. We have cloned and characterized EGD2 encoding the 27-kDa protein and
      found that Egd2p is strikingly similar to the alpha subunit of human NAC. Yeast,
      therefore, contains a complex composed of Egd1p and Egd2p very similar to the NAC
      complex described in human cells. Disruption of EGD2, alone or in combination
      with an EGD1 disruption, causes no obvious phenotypes. The lack of phenotype, the
      high levels of EGD1 and EGD2 expression, and the identification of multiple human
      genes encoding NAC subunits suggest that the yeast EGD genes may be members of
      multigene families with redundant function.

PMID- 8522176
TI  - Cloning of the Candida glabrata TRP1 and HIS3 genes, and construction of their
      disruptant strains by sequential integrative transformation.
AB  - The Candida glabrata (Cg) TRP1 and HIS3 genes have been isolated by
      complementation of the Saccharomyces cerevisiae (Sc) trp1 and his3 mutants,
      respectively. Cg TRP1 encodes a polypeptide of 217 amino acids (aa), whose aa
      sequence is 58% identical to that of Sc TRP1. Cg HIS3 encodes a polypeptide of
      210 aa, whose aa sequence is 73% identical to that of the Sc HIS3. Both Cg TRP1
      and HIS3 were disrupted by sequential integrative transformation where the Sc
      URA3 was used as a selection marker for transformation. The resulting auxotrophic
      strain of his3- and trp1- was used to examine the ability of the Sc genes to
      complement the Cg mutations; Sc HIS3 and TRP1 complemented the Cg his3- and trp1-
      mutations, respectively.

PMID- 8522177
TI  - Identification of peptide synthetase-encoding genes from filamentous fungi
      producing host-selective phytotoxins or analogs.
AB  - Race 1 of Cochliobolus carbonum (Cc) makes a cyclic tetrapeptide, HC-toxin, that
      is necessary for its virulence on certain genotypes of maize. The synthesis of HC
      toxin is catalyzed by a 570-kDa multifunctional enzyme, HC-toxin synthetase
      (HTS). The gene encoding HTS (HTS1) is absent from other races of Cc and from
      other species of Cochliobolus. Four other unrelated filamentous fungi make cyclic
      peptides closely related to HC-toxin, raising the possibility that the
      corresponding cyclic peptide synthetase (CPS)-encoding genes have moved between
      these fungi by horizontal gene transfer. Degenerate PCR primers were designed
      based on several highly conserved amino acid (aa) motifs common to known CPS
      domains and used to amplify genomic sequences from different fungi. PCR products
      representing CPS genes from Diheterospora chlamydosporia, which makes the HC
      toxin analog chlamydocin, Cylindrocladium macrosporum, which makes the analog Cyl
      2, and C. victoriae, which makes the unrelated cyclic pentapeptide victorin, were
      cloned and analysed. Their sequences are more related to HTS1 than to other
      cloned CPS, but the percent aa identity is not consistent with very recent
      horizontal movement of these genes.

PMID- 8522178
TI  - Stable DNA transformation of Toxoplasma gondii using phleomycin selection.
AB  - Toxoplasma gondii (Tg) is an obligate intracellular protozoan parasite that is an
      important opportunistic pathogen in humans. To provide additional tools for
      molecular genetic analysis, we have developed a set of vectors for DNA
      transformation in Tg based on selection with the antibiotic phleomycin (Ph).
      These new vectors rely on the flanking sequences from the parasite genes GRA1,
      GRA2 or SAG1 to drive expression of the Tn5 ble gene encoding resistance to the
      DNA intercalating drug Ph (PhR). Treatment of extracellular parasites was used to
      select stable PhR transformants by plaque formation on host cell monolayers.
      Transfection of linear or circular forms of the pGRA1/ble, pGRA2/ble or pSAG1/ble
      vectors by electroporation resulted in stable transformation with an efficiency
      of approx. 10(-4)/micrograms DNA. Stable transformants contained 1-5 copies of
      ble that were integrated at non-homologous sites in the parasite nuclear genome.
      Ble provides a new dominant selectable marker for safe, efficient and rapid
      isolation of stable DNA transformants in Tg.

PMID- 8522179
TI  - Cloning of two cDNAs encoding calnexin-like and calreticulin-like proteins from
      maize (Zea mays) leaves: identification of potential calcium-binding domains.
AB  - Two cDNAs encoding calnexin (Cln)-like and calreticulin (Crl)-like proteins have
      been isolated by immunoscreening of a maize leaf cDNA library. In the deduced
      amino acid (aa) sequences, several regions that are conserved for Cln and Crl
      proteins from all sources have been identified. These regions can be classified
      into two distinct motifs which are repeated four times each in Cln and three
      times each in Crl sequences. One of these motifs, containing a highly acidic 17
      aa sequence, has high homology to a Ca(2+)-binding domain previously
      characterized in both Cln and Crl from mammalian tissues. Motifs for retention in
      endoplasmic reticulum (Crl) and for an integral membrane-spanning sequence (Cln)
      have also been identified.

PMID- 8522180
TI  - Cloning and characterization of a cDNA encoding an 18.0-kDa class-I low-molecular
      weight heat-shock protein from rice.
AB  - A novel cDNA clone, Oshp18.0 cDNA, encoding a rice (Oryza sativa L. cv. Tainong
      67) 18.0-kDa heat-shock protein (HSP), was isolated from a cDNA library of heat
      shocked rice seedlings by use of the rice HSP cDNA, Oshsp17.3 cDNA, as a probe.
      The sequence showed that Oshsp18.0 cDNA contains a 749-bp insert encoding an ORF
      of 160 amino acids, with a predicted molecular mass of 18.0 kDa and a pI of 7.3.
      Sequence comparison reveals that Oshsp18.0 cDNA is highly homologous to other low
      molecular-weight (LMW) HSP cDNAs. Also, the results of hybrid-selected in vitro
      translation clearly establish that Oshsp18.0 cDNA is the rice 18.0-kDa LMW HSP
      encoding cDNA clone. The recombinant Oshsp18.0 fusion protein produced in
      Escherichia coli was of the size predicted, and was recognized by the class-I
      rice 16.9-kDa HSP antiserum. The results suggest that Oshsp18.0 cDNA is an 18.0
      kDa class-I LMW HSP- encoding cDNA clone from rice.

PMID- 8522181
TI  - Extrachromosomal circular forms of the tobacco retrotransposon Tto1.
AB  - Extrachromosomal DNA forms of Drosophila retrotransposons (RTn) and retroviruses
      have been extensively analyzed. However, no such analysis with plant RTn has been
      reported. Here, we report the analysis of extrachromosomal forms of the tobacco
      RTn Tto1. Tto1 is one of a few active RTn of plants and has been shown to be
      activated in tissue culture. Extrachromosomal circular DNA forms of Tto1, with
      one or two long terminal repeats (LTR), were found in cultured cells. Sequence
      analysis of the sites of circularization through joining two LTR showed that the
      junction between the LTR contains small deletions and/or insertions. The
      insertions are heterogeneous and do not show any homology to the Tto1 sequence.
      Similar insertions have been detected in the extrachromosomal circular forms of
      the copia element of Drosophila and suggested to be the result of excision of
      genomic copia. The structural features of the junctions found in Tto1 suggest
      that the insertions are produced by a mechanism other than excision. The
      potential mechanism of production of the extrachromosomal circular forms of Tto1
      is discussed.

PMID- 8522182
TI  - The tobacco etch viral 5' leader and poly(A) tail are functionally synergistic
      regulators of translation.
AB  - The 5' cap (m7GpppN) and the poly(A) tail of eukaryotic mRNAs work in concert to
      establish an efficient level of translation in vivo. Nevertheless, several mRNAs
      naturally lack a cap or a poly(A) tail. Determining how these messages
      effectively compete for the translational machinery not only reveals alternative
      mechanisms for translational competence, but can also underscore similarities
      between alternative mechanisms and the standard cap/poly(A) tail interaction. The
      genomic RNA of tobacco etch virus (TEV), a potyvirus, is a polyadenylated mRNA
      that naturally lacks a cap (m7GpppN) at the 5'-terminus and yet is a highly
      competitive mRNA during translation. The 144-nt 5'-leader is largely responsible
      for directing efficient translation and can greatly increase the translational
      competence of reporter mRNAs. We have examined the synergy between the TEV 5'
      leader and the poly(A) tail in transfected plant and animal cells. The TEV 5'
      leader functioned optimally as a regulator of reporter mRNA translation only when
      a poly(A) tail was present. The effect of the TEV 5'-leader on the translation of
      capped transcripts was significantly less than that for uncapped mRNAs,
      suggesting that the TEV 5'-leader and the cap may promote similar steps in
      translation.

PMID- 8522183
TI  - A cDNA encoding ribosomal protein L3 from the parasitic nematode Toxocara canis.
AB  - A cDNA encoding the ribosomal (r) protein L3 of the parasitic nematode Toxocara
      canis was isolated from a library constructed from mRNA of the infective larval
      stage. The encoded protein has a high degree of similarity to r-protein L3 from
      other organisms, including mammals, yeast, plants and bacteria. The mRNA encoding
      r-protein L3 is derived from a single-copy gene, and experimental evidence would
      suggest that it contains the pan-nematode splice leader sequence at its 5' end
      and that the gene is interrupted by at least three introns.

PMID- 8522185
TI  - Mollusk genes encoding lysine tRNA (UUU) contain introns.
AB  - New intron-containing genes encoding tRNAs were discovered when genomic DNA
      isolated from various animal species was amplified by the polymerase chain
      reaction (PCR) with primers based on sequences of rabbit tRNA(Lys). From
      sequencing analysis of the products of PCR, we found that introns are present in
      several genes encoding tRNA(Lys) in mollusks, such as Loligo bleekeri (squid) and
      Octopus vulgaris (octopus). These introns were specific to genes encoding
      tRNA(Lys)(CUU) and were not present in genes encoding tRNA(Lys)(CUU). In
      addition, the sequences of the introns were different from one another. To
      confirm the results of our initial experiments, we isolated and sequenced genes
      encoding tRNA(Lys)(CUU) and tRNA(Lys)(UUU). The gene for tRNA(Lys)(UUU) from
      squid contained an intron, whose sequence was the same as that identified by PCR,
      and the gene formed a cluster with a corresponding pseudogene. Several DNA
      regions of 2.1 kb containing this cluster appeared to be tandemly arrayed in the
      squid genome. By contrast, the gene encoding tRNA(Lys)(CUU) did not contain an
      intron, as shown also by PCR. The tRNA(Lys)(UUU) that corresponded to the
      analyzed gene was isolated and characterized. The present study provides the
      first example of an intron-containing gene encoding a tRNA in mollusks and
      suggests the universality of introns in such genes in higher eukaryotes.

PMID- 8522184
TI  - A multifunctional Urechis caupo protein, PAPS synthetase, has both ATP
      sulfurylase and APS kinase activities.
AB  - The synthesis of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) from inorganic
      sulfate and ATP requires two enzymes, ATP sulfurylase (SUL) and adenosine-5'
      phosphosulfate kinase (KIN). In bacteria, fungi, yeast and plants, the two
      enzymes are present on separate polypeptide chains. We have identified the first
      animal gene coding for these enzymes. In the marine worm, Urechis caupo (Uc),
      both SUL and KIN are present on a single polypeptide chain. This protein, which
      we call PAPS synthetase (PAPSS), is able to complement yeast mutants lacking
      either enzyme. The Uc PAPSS mRNA is present in oocytes, but is not translated
      until after fertilization. At least three adult tissues, gut, ceolomocytes and
      body wall, also contain the mRNA, but at lower concentrations than are found in
      embryos. Partial sequences of a similar gene from Caenorhabditis elegans (Ce)
      were detected in a search of the GenBank expressed sequence tag database.
      Comparison of these Uc and Ce PAPSS sequences with the sequences of cloned genes
      from non-animal organisms strongly suggests that the animal genes evolved through
      the fusion of the SUL- and KIN-encoding genes from lower organisms.

PMID- 8522186
TI  - Characterization of the mouse pancreatic/mammary gland cholesterol esterase
      encoding cDNA and gene.
AB  - Pancreatic cholesterol esterase (CEase) is involved in cholesterol ester
      hydrolysis and transport of cholesterol into intestinal cells. Isolation and
      sequencing of the mouse CEase cDNA indicates that the murine enzyme is very
      similar to the human enzyme, with the exception of the highly repeated C-terminal
      Pro-rich repeats. Reverse transcription-polymerase chain reaction analysis
      reveals that the message is synthesized in the pancreas of mice, but not in the
      liver.

PMID- 8522187
TI  - Genomic organization and characterization of a three-gene rat adult beta-globin
      haplotype.
AB  - The isolation and detailed characterization of a three-beta-globin gene (GloB)
      haplotype in the Sprague-Dawley (S-D) rat is described. An enriched library,
      lambda SDHelib, was screened with a human GloB probe, humbg44, and from which a
      beta minor gene, Rathbbz, was isolated, sequenced and characterized. A S-D rat
      GloB-specific probe, Ratbgze12, derived from the Rathbbz gene, was then used to
      screen a S-D rat genomic library, lambda SDglib. The clone T1510 was isolated and
      identified to include the entire Rathbbz gene and part of another GloB gene,
      Rathbby, which was 5' upstream from Rathbbz. Chromosomal walking upstream using
      the riboprobe, rnaT71, led to the isolation of an overlapping clone, Ta49, which
      was shown to include two full-length GloB genes; the most 5' was Rathbbx followed
      by Rathbby. Sequence data suggests that Rathbbx is a beta major gene, whereas
      Rathbby is a hybrid gene of Rathbbx and Rathbbz. Genomic hybridization confirmed
      this particular three-gene haplotype in the S-D rat. This haplotype, a1, may be
      the prototype of the GloB cluster in rat.

PMID- 8522188
TI  - Cloning of a rat cDNA encoding a novel LIM domain protein with high homology to
      rat RIL.
AB  - A complementary DNA (1392 bp) encoding a protein with high homology to rat
      reversion-induced LIM (RIL) protein was cloned from rat hepatocytes by
      differential screening of a subtractive (normoxic minus hypoxic) lambda GEM-2
      cDNA library. This cDNA clone, denoted CLP-36, encodes a 327-amino-acid (aa)
      protein that contained a restrictively conserved LIM (a Cys-rich domain with
      consensus aa sequence C-X2-C-X17-19-H-X2-C-X2-C-X2-C-X16-20-C-X2-C/H/D that was
      initially identified in homeodomain proteins, Lin-11 [Freyd et al., Nature 344
      (1990) 876-879], Isl-1 [Karlsson et al., Nature 344 (1990) 879-882] and Mec-3
      [Way et al., Cell 54 (1988) 5-16] in the C-terminal portion (aa 192-327). It
      shared an overall 45.1% identity to a rat LIM domain RIL protein [Kiess et al.,
      Oncogene 10 (1995) 61-68], with 62.0% identity in the N terminus (aa 1-89) and
      50.0% identity in the C terminus (aa 188-327). The rat CLP-36 mRNA is expressed
      most abundantly in heart, lung and liver, moderately in spleen and skeletal
      muscle, and at extremely low levels (if at all) in testis and brain tissues.
      Northern blotting analysis of total RNA extracted from normoxic or hypoxic rat
      hepatocytes, with a fragment of clone CLP-36 as probe, demonstrated a single band
      with a mobility corresponding to a size of 1.4 kb, whose level was significantly
      decreased during chemical hypoxia.

PMID- 8522189
TI  - Differential expression of CAP and CAP2 in adult rat tissues.
AB  - We previously reported the identification of the human CAP and CAP2 genes which
      encode proteins related to the yeast adenylyl cyclase (CYR)-associated CAP
      protein. The rat CAP homolog, MCH1, has also been previously cloned. We have
      cloned a cDNA encoding the rat homolog of CAP2. Rat CAP/MCH1 and CAP2 are 63%
      identical to each other. Using the reverse transcription-polymerase chain
      reaction (RT-PCR) method, we have examined CAP/MCH1 and CAP2 mRNA levels in
      various adult rat tissues. Our results show a dramatic difference in the pattern
      of expression of these two genes. Consistent with previous reports, we detected
      CAP/MCH1 mRNA in all tissues examined; however, levels vary substantially between
      tissues. In particular, we found that CAP/MCH1 mRNA are present at relatively
      high levels in spleen, testes and lung, at moderate levels in brain, kidney,
      liver and small intestine, and at significantly lower levels in heart, skeletal
      muscle and skin. We have also investigated the levels of CAP/MCH1 in rat tissues
      by immunoblotting with a polyclonal antibody raised against a human CAP::GST
      fusion protein. In general, we find that the CAP/MCH1 mRNA levels reflect the
      amount of CAP/MCH1 found in different tissues. In contrast, CAP2 transcripts were
      present at relatively high levels in testes, at moderate levels in brain, heart
      and skeletal muscle, at lower levels in lung, skin, kidney and small intestine,
      and were undetectable in liver or spleen. The differences between the sequences
      and expression patterns of CAP/MCH1 and CAP2 are significant and suggest that
      these proteins have distinct functional roles.

PMID- 8522190
TI  - Cloning of the rat ErbB3 cDNA and characterization of the recombinant protein.
AB  - Three cDNA fragments that encoded all but the extreme N terminus of the rat ErbB3
      protein were cloned by low-stringency screening of a rat liver cDNA library with
      a human ERBB3 probe. The remaining 5'-end of the cDNA was generated by a reverse
      transcription-polymerase chain reaction method, and a single full-length rat
      ErbB3 cDNA was assembled. A comparison of the deduced amino acid (aa) sequences
      of human and rat ErbB3 was made, and the effects of certain aa substitutions in
      the putative protein tyrosine kinase domain were considered. The rat ErbB3 cDNA
      was subsequently expressed in cultured NIH-3T3 mouse fibroblasts, in which a high
      level of approx. 180-kDa recombinant ErbB3 (re-ErbB3) was generated. The rat re
      ErbB3 produced in transfected fibroblasts was responsive to the polypeptide,
      heregulin, a known ligand for ErbB3. Challenge of transfected fibroblasts with
      heregulin stimulated the phosphorylation of rat re-ErbB3 on Tyr residues and
      promoted its association with the p85 subunit of phosphatidylinositol 3-kinase.
      Together, these results indicate that a fully functional rat ErbB3 cDNA has been
      isolated, and that fibroblast cells expressing this cDNA will be suitable for
      investigations of the signal transduction mechanism of ErbB3.

PMID- 8522191
TI  - The upstream region of the SP-B gene: intrinsic promoter activity and
      glucocorticoid responsiveness related to a new DNA-binding protein.
AB  - We identified and cloned the rabbit SP-B gene, encoding the pulmonary surfactant
      associated protein, and sequenced its upstream region from -2635 to +428,
      including a much larger fragment of the upstream region than has previously been
      reported for an SP-B for any species. Rabbit SP-B showed substantial homology to
      its human counterpart in the coding and noncoding regions immediately upstream
      from the TATAA box. Using a luciferase (Luc) reporter gene (luc) construct we
      measured promoter activity with a 212-bp fragment (SPB212) from nucleotides (nt) 
      41 to -252, inclusive. SPB212 functioned as an active promoter in this assay.
      Further, we identified, cloned and sequenced the cDNA encoding a unique DNA
      binding protein, N, that bound SPB212 at approx. -195. When the N cDNA was cloned
      into the expression vector pKC4 and cotransfected with the luc reporter
      construct, N significantly enhanced Luc production, but only in the presence of
      dexamethasone. Therefore, we identified and sequenced a functional promoter
      region upstream from rabbit SP-B, and isolated and characterized a DNA-binding
      protein that confers enhanced glucocorticoid responsiveness on this promoter.

PMID- 8522192
TI  - High-level, stage- and mammary-tissue-specific expression of a caprine kappa
      casein-encoding minigene driven by a beta-casein promoter in transgenic mice.
AB  - A 5' truncated caprine (ca) kappa-casein-encoding gene (kappa Cas) was fused to
      the 3' end of a 3' truncated ca beta Cas. The kappa Cas form comprised the 0.8-kb
      3' end of intron 2, the remaining part of the transcription unit containing
      codons -2 to stop 172, and 0.43 kb of the 3' flanking region. The beta Cas form
      comprised a 3-kb 5' flanking region and the 5' end of the transcription unit
      terminating 69 bp downstream from exon 2 which encodes the 15-amino-acid (aa)
      signal peptide and the first 2 aa of mature beta Cas. The resulting hybrid gene
      driven by the beta Cas promoter was expressed in all eight lines of transgenic
      mice investigated, although at different levels. In two lines, the yield of
      recombinant (re-) kappa Cas was > or = 3 mg/ml of milk. The stage- and mammary
      tissue-specific expression was similar to that of endogenous beta Cas. The re
      kappa Cas differed from its goat milk counterpart by the occurrence of four extra
      aa at the N-terminal end, indicating that the signal peptidase released the beta
      Cas signal peptide. According to sedimentation analyses of murine milk containing
      > or = 3 mg re-kappa Cas/ml, the latter essentially occurred in micelles.
      Preliminary comparative assays of the behavior of ca alpha s1Cas-kappa Cas and
      alpha s1Cas-re-kappa Cas mixtures upon incremental addition of Ca2+ showed that
      re-kappa Cas had the capacity to protect alpha s1Cas against Ca(2+)-induced
      precipitation in forming stable micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522193
TI  - The human ribosomal protein S7-encoding gene: isolation, structure and
      localization in 2p25.
AB  - We have identified a gene encoding the human ribosomal protein (r-protein) S7.
      The S7 gene contains seven exons and six introns spanning about 6 kb.
      Organization of the gene is similar to that of Xenopus laevis S8, the only
      homologous intron-containing gene isolated so far. An mRNA transcribed from this
      gene has an open reading frame (ORF) of 582 nucleotides (nt), which encodes a
      protein of 194 amino acids (22.1 kDa). The transcription start point (tsp) was
      mapped by a primer extension assay to a C residue within a pyrimidine-rich tract.
      Human S7 (hS7) is identical to rat S7 (rS7) and exhibits significant similarity
      with the X. laevis, insect and plant homologs. We have used fluorescence in situ
      hybridization (FISH) to localize S7 to chromosome 2p25.

PMID- 8522194
TI  - High-level production and one-step purification of biologically active human
      growth hormone in Escherichia coli.
AB  - A plasmid has been constructed to direct the synthesis of recombinant human
      growth hormone (re-hGH) in Escherichia coli as a fusion protein containing a His6
      tag at the N-terminus under the control of the T5 promoter. The re-hGH was
      synthesized in large amounts and accumulated in the form of inclusion bodies upon
      induction with IPTG. Inclusion bodies were solubilized in 6 M guanidine.HCl and
      the re-hGH was purified by single-step affinity chromatography on Ni(2+)
      nitrilotriacetic acid (NTA) agarose. At the shake flask level, the purified re
      hGH was obtained with a yield of 30 mg/l of culture. The re-hGH was biologically
      active in a node rat lymphoma (Nb2) cell bioassay.

PMID- 8522195
TI  - Cloning and characterization of the human 5,10-methenyltetrahydrofolate
      synthetase-encoding cDNA.
AB  - Methenyltetrahydrofolate synthetase (MTHFS) catalyses the obligatory initial
      metabolic step in the intracellular conversion of 5-formyltetrahydrofolate to
      other reduced folates. We have isolated and sequenced a human MTHFS cDNA which is
      872-bp long and codes for a 203-amino-acid protein of 23,229 Da. Escherichia coli
      BL21(DE3), transfected with pET11c plasmids containing an open reading frame
      encoding MTHFS, showed a 100-fold increase in MTHFS activity in bacterial
      extracts after IPTG induction. Northern blot studies of human tissues determined
      that the MTHFS mRNA was expressed preferentially in the liver and Southern blot
      analysis of human genomic DNA suggested the presence of a single-copy gene.

PMID- 8522196
TI  - Production of human gastric lipase in the fission yeast Schizosaccharomyces
      pombe.
AB  - A cDNA encoding human gastric lipase (hGL) has been expressed on multicopy
      plasmids in the fission yeast Schizosaccharomyces pombe (Sp). Active lipase is
      secreted from transformants containing the hGL cDNA under the control of either
      the Sp adh1 promoter (Padh1) or the plant cauliflower mosaic virus (CaMV) 35S
      promoter. Cell-wall-associated lipase activities are greatest in the early
      logarithmic growth phase and with Padh1. Western blot analysis indicates that a
      protein of identical molecular mass to natural hGL is secreted by Sp, although
      the major secreted product is of a higher molecular mass than either native hGL
      or recombinant hGL produced in the budding yeast Saccharomyces cerevisiae (Sc).
      Several distinct hGL are present within cells at all growth phases. Treatment of
      these proteins with endoglycosidase H gives rise to a single species equivalent
      in size to deglycosylated natural hGL, indicating that most of these are
      glycosylation intermediates. An hGL of similar molecular mass accumulates
      intracellularly in Sp when a modified version of cDNA is used which lacks the
      sequence encoding the natural secretory signal peptide. Production of hGL
      markedly slows the growth rate of Sp. The average copy number per cell of the
      plasmid expressing the hGL cDNA from the recombinant Padh1 is 2-3, as compared
      with 11-12 for the control plasmid.

PMID- 8522197
TI  - Identification of non-tissue-specific helix-loop-helix genes in Xenopus laevis.
AB  - We have isolated four non-tissue-specific helix-loop-helix (HLH) transcription
      factors from Xenopus laevis (Xl). While some are clearly orthologous to known
      mammalian HLH proteins, others have dramatic amino-acid differences in otherwise
      highly conserved protein domains. We propose that these changes arose following
      the tetraploidization of Xl approx. 30 Myr ago.

PMID- 8522198
TI  - Sequence of the flounder (Paralichthys olivaceus) growth hormone-encoding gene
      and its promoter region.
AB  - The flounder (Paralichthys olivaceus) growth hormone (GH)-encoding gene (fGH) and
      its promoter region were cloned and sequenced following amplification of genomic
      DNA by the polymerase chain reaction. The fGH gene is 2.1-kb long and consists of
      six exons and five introns. In the 5'-flanking region of the determined
      transcription start point, a potential TATA box is located at -24, and Pit-1/GHF
      1-binding site candidates are located in the -70 to -53 and -133 to -141 regions.

PMID- 8522199
TI  - Sequences of the cDNAs encoding the heavy- and light-chain Fab region of an
      antibody to the phenylurea herbicide diuron.
AB  - The cDNAs from a hybridoma (mAb 481.1) specific for diuron, a widely used
      phenylurea herbicide, were cloned into the phage display vector pComb8. Antigen
      binding clones were selected by panning on diuron-hapten-BSA conjugates. The
      nucleotide and deduced amino-acid sequences encoding the Fab regions of the light
      (kappa) and heavy (gamma) chains were determined. The light chain was from mouse
      kappa chain subgroup III and the heavy chain was a member of the mouse H chain
      subgroup III(d).

PMID- 8522200
TI  - Molecular organization of the gene encoding murine transforming growth factor
      beta 1.
AB  - A detailed restriction map of the murine TGF-beta 1 locus (encoding transforming
      growth factor beta 1) was established and the precise junctional sequences of its
      seven exons and corresponding introns were elucidated. While the exons ranged in
      size from 78 to 357 bp, the introns ranged from about 1 to 6.5 kb. The promoter
      proximal segment contains many putative regulatory motifs which may dictate TGF
      beta 1 gene transcription in response to varied pathophysiological stimuli.

PMID- 8522201
TI  - Aberrant splicing of rat steroid 17 alpha-hydroxylase transcripts.
AB  - Polymerase chain reaction amplification of the cDNA encoding steroid 17 alpha
      hydroxylase (P450c17) demonstrated very low levels of this transcript and a
      shorter variant of still lower abundance in rat adrenals and brain. Sequence
      analysis of the two amplified products revealed that the shorter variant resulted
      from a deletion of the second exon which does not maintain the open reading
      frame, suggesting that faulty splicing gave rise to this minor species.

PMID- 8522202
TI  - Cloning of a cDNA encoding rat bone marrow stromal cell antigen 1 (BST-1) from
      the islets of Langerhans.
AB  - We have isolated the rat bone marrow stromal cell antigen 1-encoding cDNA (BST-1)
      from a pancreatic islet cDNA library. The cDNA encodes a 319-amino-acid (aa)
      protein whose aa sequence shows homology with mammalian CD38 (33%), Aplysia ADP
      ribosyl cyclases (33%), as well as mouse (86%) and human (72%) BST-1.

PMID- 8522203
TI  - The sequence of the rat pyruvate carboxylase-encoding cDNA.
AB  - A composite 3945-bp cDNA that encodes rat pyruvate carboxylase (PC) has been
      constructed from clones isolated from a rat liver cell cDNA library and the
      nucleotide sequence has been determined. The rat cDNAs open reading frame encodes
      a protein of 1178 amino acids that is 98.6% identical (99.0% similar) to that of
      mouse PC and 96.0% identical (97.8% similar) to that of human PC.

PMID- 8522204
TI  - Cloning, sequencing and expression of the gene encoding a major allotypic
      preprocarboxypeptidase A from bovine pancreas.
AB  - A cDNA encoding one of two major allotypic forms of bovine pancreatic
      preprocarboxypeptidase A (preproCPA) has been cloned, and its entire nucleotide
      (nt) sequence determined. The cloned cDNA contains a 26-nt 5'-noncoding region, a
      1260-nt open reading frame and a 51-nt 3'-noncoding region. The amino acid (aa)
      sequence deduced from the gene sequence contains Ile179, Ala228 and Val305 at
      allotypic aa residues. The procarboxypeptidase A (proCPA) was produced in yeast
      and secreted into the medium. Upon treatment with trypsin, proCPA generated an
      active enzyme with the same size as the mature carboxypeptidase A (CPA), as
      analyzed by use of anti-CPA polyclonal antibody.

PMID- 8522205
TI  - Interferon induction of human tryptophanyl-tRNA synthetase safeguards the
      synthesis of tryptophan-rich immune-system proteins: a hypothesis.
AB  - Ever since the discovery that the human tryptophanyl-tRNA synthetase (TrpRS)
      encoding gene is induced by interferon (IFN) [J. Fleckner et al., Proc. Natl.
      Acad. Sci. USA 88 (1991) 11520-11524] and contains IFN-response regulatory
      elements [Frolova et al., Gene 128 (1993) 237-245], the biological rationale for
      this induction has remained unresolved. A survey of immune system proteins in
      this study reveals that the human major histocompatibility complex (MHC)
      antigens, beta-2-microglobulin (beta MG) and complement factor B, which are known
      to be induced by IFN, together with immunoglobulins (Ig) are all exceptionally
      enriched in Trp residues, as compared to human proteins in general. It also
      reveals the conservation of a sequence motif, CX10-17 WX26-62C, in Ig domains.
      The conservation of this sequence motif and the utility of Trp residues within
      antigen-binding sites clearly contribute to the Trp enrichment in Ig. These
      observations suggest a biological rationale for the induction of TrpRS by IFN in
      safeguarding Trp incorporation for the IFN-enhanced synthesis of immunological
      molecules.

PMID- 8522206
TI  - [An analysis of indications for performing cesarean section from material of the
      Obstetric-Gynecologic Wards I and II of the District General Hospital in Radom in
      1985-1993].
AB  - In 1985-1993 there were 37,046 deliveries in the Maternity and Gynaecological
      Ward of District General Hospital in Radom. In 4873 (13.15%) cases the caesarean
      section (c.s) was performed. Primiparas constituted 39.3% and the repeated c.s.
      was carried out on 1160 (39.2%) patients. In the analysed period the increase in
      percentage of the c.s. was observed from 11.79% in 1985 to 14.81% of the total
      number of deliveries in 1993. The most frequent indications to perform the c.s.
      were the imminent intrauterine asphyxia of the fetus--25.36%, the abnormal
      position of the fetus--17.73% and the nonprogressive labour--9.89%. In all these
      groups the operations were performed in over 70% of primiparas. In the case of
      multiparas the indications to operate were: prolapse of the loop of umbilical
      cord--71%, placenta previa in 85.8% and the prematurely detached placenta in
      72.2% of cases. In 4.45% of cases the c.s. was performed as the result of other
      than obstetric indications.

PMID- 8522207
TI  - [Maternal instinct in women with complicated pregnancy].
AB  - Maternal instinct was evaluated in women with complicated pregnancy by means of
      inquiry. Perception of the first fetal movements by pregnant women in as
      important moment in maternal instinct development. Pregnant women with bad
      obstetrical history show greater anxiety about unborn yet child. Intensity of
      maternal instinct is similar in multiparas and nulliparas.

PMID- 8522208
TI  - [Point CO2 laser vaporization in treatment of superficial endometriosis of the
      uterine cervix].
AB  - The study showed the treatment of superficial endometriosis of the uterine cervix
      in 54 women between November 1991 and January 1994. After first vaporisation 43
      patients were cured successfully. In 8 cases vaporisation should be repeated and
      in 3 women the operation should be performed for the third time. All patients are
      still under control in our department and there is no recurrence observed.

PMID- 8522209
TI  - [Concentration of the complement component (C3) in blood sera of small-for
      gestational age newborns and their mothers].
AB  - 36 small-for-dates newborn were introduced to our studies. The concentrations of
      C3 in sera of newborns were at 65% mean values found in sera their mothers. We
      have compared the concentrations of C3 in sera of newborns and their mothers and
      did not find no correlation. These data may indicate this component does not
      penetrate through placenta.

PMID- 8522210
TI  - [Contemporary views on use of estrogen replacement therapy in postmenopausal
      women. I. Hormone therapy in women with menopausal osteoporosis].
AB  - Osteoporosis is a great problem in postmenopausal women. It begins 4--5 years
      after a last period and appears in clinical form in about 25-44% women. Basic
      irregularity is osteopenia as a result of bone resorption superiority. Many
      observations lead to conclusion that postmenopausal osteoporosis follows
      estrogens deficiency, that play a substantial role in bone metabolism. Estrogen
      therapy reverses a process of osteoporosis. Periodic treatment, with use of
      progestogens, should be performed, under condition of close endometrium and
      breast control. Progestogens also increase, depending on dose and kind of
      hormone, mechanisms preventing bone mass lost.

PMID- 8522211
TI  - [The evaluation of ovarian tumor vascularization using color Doppler transvaginal
      ultrasonography].
AB  - The aim of this study was the evaluation of blood flow factors prognostical value
      in differentiation of malignancy among ovarian tumors--sensitivity of this method
      was 81.8--90.9%, specificity was 88.5%, positive predict value 75.0--76.9% and
      negative predict value 92.0--95.8%. It was stated that Dopplers method is very
      usefull in diagnosis of malignant ovarian neoplasms. Moreover it was shown that
      pulsation index (PI) is more suitable than resistance index (RI), particularly in
      preoperative diagnostics.

PMID- 8522212
TI  - [Most common neoplasms of female genital organs and hypo-thalamic-hypophysial
      ovarian regulation in the postmenopausal period].
AB  - Levels of FSH, LH and E2 were evaluated by means of EIA methods in 62 post
      menopausal women qualified for operation treatment. In 46 cases neoplasms of
      uterus body and in 16 cases neoplasms of uterus cervix and an ovary were stated.
      Higher level of estradiol and lower levels of gonadotrophins were shown in cases
      with uterus body neoplasms and opposite, lower estradiol levels and higher
      gonadotrophins values in cases with cervix and ovarian neoplasms. The outcome
      suggests possibility of function of hypothalamic-hypophysial-ovarian axis in post
      menopausal period. Level of estradiol can be also used as a diagnostic marker to
      uterus body neoplasms.

PMID- 8522213
TI  - [Ovarian cancer and selected life style habits].
AB  - Analysis of population based case-control study performed in Cracow Poland in
      1988-1990 on 81 cases of histologically proven epithelial ovarian cancer and 162
      age matched controls have shown that frequent consumption of legumes was
      associated with significantly decreased risk. Smoking and drinking of vodka were
      not significant related to ovary cancer risk.

PMID- 8522214
TI  - [Evaluation of 5-year surgical treatment outcome in patients with vulvar tumors].
AB  - A retrospective study of all patients with carcinoma of the vulva treated by
      surgery and/or radiation therapy, between 1980 and 1985, is reported. Sixty eight
      patients were analyzed for survival, recurrence patterns, complications and
      clinical features. The stages of disease were as follows: Stage I or II 49 pts,
      Stage III 13 pts and Stage IV 6 pts. The 5-year survival rate was 45.2%.
      Recurrences were diagnoses in 25% of the patients. With the less aggressive
      surgical approach used, combined with radiation therapy to eradicate subclinical
      disease, the morbidity rate was acceptable and the survival rate comparable to
      the reported after more aggressive surgery.

PMID- 8522215
TI  - [Kidney function in pregnant women with arterial hypertension].
AB  - In a group of 80 women in their 3rd trimester of pregnancy (29-36 weeks) 50 of
      whom were with hypertension and 30 healthy, the blood serum was studied for
      concentrations of urea, uric acid, creatinine, total proteins and electrolytes:
      sodium and potassium. The results were calculated statistically. In the serum of
      women with hypertension increased concentrations of urea and uric acid were
      found. Total protein concentration was lower in the studied group, especially
      those with primary arterial hypertension. Whereas concentration values of
      electrolytes Na+ and K+ did not seem to be affected by hypertension.

PMID- 8522216
TI  - [Anti-Mullerian hormone. Structure and role in sexual differentiation].
AB  - Anti-mullerian hormone (AMH) which plays a key role in male sexual
      differentiation is a glycoprotein, produced by Sertoli cells. In male fetuses AMH
      is responsible for regression of Mullerian duct, the analgen of uterus, the
      Fallopian tubes, and 2/3 upper of the vagina, while in female fetuses for a
      decrease in aromatase activity in granulosa cells of the ovary. Human AMH gene
      consists of 5 exons: 412, 124, 108, 160 and 856 bp in length, and is localized
      near the tip of chromosome 19, in subbands 13.2 to 13.3. Mutations of the gene or
      the receptor of AMH are responsible for clinical symptoms of Persistent Mullerian
      Duct Syndrome (PMDS) which occurs in subjects with a karyotype 46XY and a male
      phenotype. Typical case is that of a male with bilateral cryptorchidism and
      inguinal hernias but normal male genitalia. Uterus and Fallopian tubes are often
      present in the inguinal canal. In this review data from literature are presented
      and discussed regarding the structure and function of the AMH and its role in
      male sexual differentiation.

PMID- 8522217
TI  - [Carcinoid syndrome in a pregnant woman. Case report].
AB  - The carcinoid syndrome was discussed based on the reference materials. The aim of
      the work is to present the course of pregnancy ended by the delivery of a full
      term healthy child by a 32-year-old multipara with the carcinoid syndrome
      diagnosed 3 years earlier.

PMID- 8522218
TI  - [The effect of hypertension severity in pregnant women and during birth on renal
      function].
AB  - In a study of 50 women in their 3rd trimester of pregnancy complicated by
      hypertension of different etiology, the blood serum was examined for
      concentrations of urea, uric acid, creatinine, total proteins, sodium and
      potassium. The results were calculated statistically. It was found that the
      degree of hypertension severity increases concentrations of uric acid, with no
      significant changes in the values the remaining parameters. There were no
      differences found in biochemical tests of renal efficiency between primiparous
      and multiparous pregnancies complicated by hypertension.

PMID- 8522219
TI  - [Fetal metabolism in post term pregnancy based on biochemical investigations of
      amniotic fluid. IV. Ion composition].
AB  - Concentrations of calcium, sodium, magnesium, calcium (total and ionised) and
      inorganic phosphorus were determined in amniotic fluid. Samples were taken from
      patients between 42-43 week of gestation (investigated group) and between 38 and
      40 week (control group). Micro-methods, generally acknowledged in laboratories of
      clinical biochemistry were used. In the protracted pregnancies increase of
      magnesium levels and decrease of sodium levels were observed. No differences in
      concentrations of calcium, calcium (total and ionised) and inorganic phosphorus
      between investigated and control group were noted. Independently of the duration
      of pregnancy, near term or post term, ionised calcium constituted 90% of total
      calcium in amniotic fluid.

PMID- 8522220
TI  - [Fetal metabolism in post-term pregnancy based on biochemical examinations of
      amniotic fluid. V. Glucose, bilirubin, H+ ions, hormones and tests of lung
      maturation].
AB  - Concentrations of glucose, bilirubin, H+ ions, estriol, HPL were determined in
      the samples of amniotic fluid from post term and near term pregnancies.
      Investigated group consisted of samples taken between 42-43 week of gestation,
      control group between 38-40 week. In both groups biochemical tests of pulmonary
      maturation--Lectin/Sphingomyelin ratio, foam test, 650 nm absorbance were carried
      out. In the diagnosis of post term pregnancy glucose concentrations, oestrogens,
      HPL, 650 nm adsorption, foam test and L/S ratio had proper diagnostic value. No
      differences were observed in bilirubin concentrations.

PMID- 8522221
TI  - [Early amniocentesis in prenatal diagnosis].
AB  - In the period 1990-1991 483 prenatal diagnosis were carried out. Of those in 111
      (23%) the technique of early amniocentesis was used, i.e. between 12th and 14th
      weeks of gestation. In 23 cases the result of cytogenetical diagnosis was
      positive. The time necessary for obtaining the result did not differ from that of
      amniocentesis performed at 15-20 weeks of gestation. The cytogenetical
      examination was successful in all cases of early amniocentesis.

PMID- 8522222
TI  - [Mineral components of the human placenta, birth weight and infant head
      circumference].
AB  - Levels of mineral elements (F, Na, Mg, Al, S, Cl, K, Ca, V, Cr, Mn, Fe, Co, Cu,
      Zn, Se, Br, Rb, Mo, Cd, J, Ba, Hg and Pb), the role of which is well known and
      documented, were studied in 365 placentas. The significant negative correlations
      were ascertained between the content of Pb, Cd, F, Hg and the birth weight; the
      positive correlations were ascertained between some minerals (Mg, Ca, Co, Cu, Zn,
      Se) that are indispensable for the proper organism functioning and the fetus
      development.

PMID- 8522223
TI  - [Verification of KTG recording in states of perinatal partial asphyxia using
      fetal capillary blood pH].
AB  - We analysed 91 cases of pH-metric verifications of pre-pathological and
      pathological cardiotocograms, which suggested imminent perinatal partial
      asphyxia. In 50% of cases there was no need for medical intervention, this groups
      of patients delivered vaginally and newborns were in good condition. In 80% pH
      value well correlated with state of newborn at birth. Pre-pathological
      cardiotocograms showed mainly variable decelerations, pH value didn't show
      acidosis and afterbirth umbilical cord collision was stated. In pathological
      cardiotocograms we observed mainly late decelerations, pH value showed fetal
      acidosis which coexisted with placental insufficiency in prolonged gestation.

PMID- 8522224
TI  - [Finding antigens using immunoenzyme methods characterized by nonhistone proteins
      in hyperplastic and neoplastic endometrium in women].
AB  - Immune rabbit serum against NHCP extracted from woman endometrial adenocarcinoma
      were obtained to search for antigen in blood of patients with hyperplastic and
      neoplasmatic endometrium. The highest value of extinction were observed in
      carcinomas and hyperplastic endometrium values were similar. The lowest values
      were noted in control group with normal proliferative endometrium.

PMID- 8522225
TI  - [Analysis of menstrual cycle irregularities in adolescents].
AB  - The analysis covered 1615 teenagers, patients of Child's & Adolescents
      Gynaecology Clinic in Lodz in the years 1980-1990. 338 of them had troubles in
      the menstrual cycle. Majority of them (55.6%) claimed about algomenorrhoea, 17.6%
      had oligomenorrhoea and 10.5% had hypermenorrhoea. The examined teenagers were
      normally developed both in respect of age and gender. Age of menarche is
      relatively a little lower in Lodz, i.e. 12.4 years of age.

PMID- 8522226
TI  - [The influence of modified sequential therapy on lipid metabolism in
      postmenopausal women].
AB  - The study was performed in 50 women aged 49 to 55 years, divided into two groups.
      Group I received transdermally at a rising dose of 2 to 8 mg, altogether 16 mg
      during the therapeutic cycle of 20 days. Group II received estriol intravaginally
      0.03 mg/day 10 days and 0.06 mg/day for 10 days. During the second part of the
      therapeutic cycle all women were given progesterone sublingually 25 mg/day for 6
      days and 50/day for 6 days. Measurements in serum of total cholesterol, free
      cholesterol and triglycerides using an enzymic method, of HDL-Ch and LDL-Ch using
      a precipitation method and of cholesterol esters using thing-layer chromatography
      were performed before and after 3 months of therapy. It was found that the use of
      estradiol leads to a significant decrease in the level of triglycerides, total
      and free cholesterol, LDL-Ch, with a rise in HDL-Ch. The use of estriol leads to
      a decrease in LDL-Ch only. No changes in the composition of cholesterol esters
      were found in both groups, with the exception of an insignificant rise in the
      percentage of cholesterol oleate.

PMID- 8522227
TI  - [Procedures for Candida albicans systemic infections in premature infants].

PMID- 8522228
TI  - [Clinical effectiveness of Marvelon].
AB  - Clinical results of a new contraceptive pills--Marvelon (Organon) were studied.
      32 women, ages 30 +/- 5 years, participated in the study during at least 6
      cycles. Marvelon was good tolerated and subjective side-effects were very low.
      The cycles were regular, duration of withdrawal bleeding was 3-5 days and the
      amount of the blood lost were unchanged or milder. Marvelon didn't affect body
      weight and blood pressure. Favourable lipid profile--increased a mean level of
      HDL-Cholesterol and decreased a mean level of LDL-Cholesterol were noticed. Pearl
      Index was 0,0.

PMID- 8522229
TI  - [Significance of doppler ultrasound examination in successful termination of
      pregnancy with arterial hypertension in the course of chronic proliferative
      glomerulonephritis].
AB  - Diagnostic and therapeutic management in pregnant woman with severe arterial
      hypertension in course of glomerulonephritis proliferativa chronica at kidney
      insufficiency stage was presented. Ultrasonic biometry, biophysical fetal profile
      and Doppler ultrasound velocimetry were performed for antenatal fetal
      surveillance. Relation between a degree of fetal compromise (abnormal qualitative
      Doppler velocimetry indices and pre-pathological or even pathological NST) and a
      long-drawn increase of both diastolic and systolic blood pressure was stated.
      Doppler ultrasound examination gave possibility of monitoring and evaluation of
      fetal distress and verification of its treatment efficacy, what would allow to
      prolong the pregnancy for 12 days and was a definite contribution to its
      successful outcome.

PMID- 8522230
TI  - [Asymmetry phenomenon of the placenta. The role of Doppler examination].
AB  - Authors characterized the Doppler indices asymmetry phenomenon on two exemplary
      cases. This phenomenon is due to placenta asymmetry. The impact on methodology of
      the Doppler examination is pinpointed.

PMID- 8522231
TI  - [Acute kidney failure associated with pregnancy and delivery].
AB  - The cases of acute renal failure are presented. Severity of the disease, employed
      treatment and diagnostic problems were discussed. The early dialysis treatment at
      those patients is postulated (discussed).

PMID- 8522232
TI  - [Carcinoma on the base of the ovarian struma].
AB  - A rare case of carcinoma developed in struma ovary in 55 year-old woman. During
      surgical intervention, the carcinoma infiltration in ovary stroma was diagnosed.
      The metastases were not stated. In the immunohistochemical assay, thyroglobulin
      and cytokeratin in neoplastic cells were displayed. Clinical examination did not
      show any signs of hyperthyreosis.

PMID- 8522233
TI  - [Lupus pregnancy, its effect on the course of lupus nephritis and the evaluation
      of fetal loss frequency].
AB  - The subject of analysis were data concerning the 101 pregnancies in 43 patients
      with systemic lupus erythematodes observed in years 1965-1990. The evaluation
      proved that pregnancy does not deteriorate the course of lupus nephritis that is
      in the remission before the conception. In lupus patients the risk of fetal loss
      and stillbirth is high, especially in the presence of anticardiolipin antibodies.
      The course of active lupus occurring during pregnancy is frequently severe and
      its effect on the pregnancy is very harmful.

PMID- 8522234
TI  - [Effect of insulin therapy on duration of pregnancy in women with diabetes].
AB  - The paper compares how, in the conditions of long observed rule of relative
      pregnancy length, the length of pregnancy of women with insulin-dependent
      diabetes is maintained depending on the ways of treating and controlling
      diabetes. The observations were taken during two periods. In the years 1980-1986
      71 women were treated with insulin in traditional way--without constant
      monitoring of pregnancy, and from 1987-1992 in 232 women intensive pregnancy
      monitoring and conventional insulin therapy were used. This treatment allowed to
      achieve proper stabilizing of diabetes, to prolong pregnancy for 12 days and to
      improve the newborns condition while keeping the same indications for cesarean
      section and other ways of delivery and with the same frequency of spontaneous
      birth. In addition the number of premature births was decreased four times. From
      53.5% in the first period to 12% in the second.

PMID- 8522235
TI  - [Occurrence of Bacteroides fragilis strains in full term and post term
      pregnancies].
AB  - Bacteroides fragilis (B.f.) is an aetiological agent of gynecological and
      obstetrical infections. The aim of this study was to determine occurrence of B.f.
      in women genital tract. A total number of 118 women in labor between 38 and 43
      gestation age and not demonstrating clinical symptoms of infection was examined.
      B.f. strains were isolated from 9 women (15.9%). More often B.f. strains were
      isolated from women delivering post-term and staying previously in Pregnancy
      Pathology Ward. It was observed that infant mean weight on the 3rd day of life
      was higher in the vagina. The following features of isolates were compared:
      presence of the capsule and agglutination of sheet erythrocytes. Differences in
      haemagglutination and susceptibility to antibiotics were observed.

PMID- 8522236
TI  - [The effect of TNF-alpha (tumor necrosis factor-alpha) on progesterone synthesis
      in vitro by cells from ovarian follicular fluid in women].
AB  - Follicular fluid was obtained through the ovarian follicle puncture during
      laparotomy in seven women. Follicular cells were cultured for 66 hours in the
      presence of TNF-alpha or lipopolysaccharides. Concentration of FSH, LH and
      prolactin in follicular fluid and progesterone levels in culture medium were
      estimated. TNF-alpha (100 ng/ml medium) diminished progesterone production in 6
      hours tissue culture but reduced its concentration in 18 and 42 hours culture in
      comparison to the controls. Correlation was found between FSH level in follicular
      fluid and percentage of progesterone concentration change in experiments with TNF
      alpha 100 mg/ml up to 42 hours and with TNF-alpha 500 ng/ml up to 18 hours.
      Lipopolysaccharides (10 micrograms/ml) did not influence progesterone production
      in the tissue culture.

PMID- 8522237
TI  - [Use of planned intermittent peritoneal lavage (open abdomen) in severe forms of
      peritonitis due to gynecologic-obstetric procedures].
AB  - Five women in whom the technique of intermittent peritoneal lavage (the so called
      "open abdomen") was applied following severe diffuse peritonitis have been
      presented. The details of operational technique have been given. Four patients
      have been cured without complications. In one patient a subhepatic abscess
      occurred but it was successfully operated.

PMID- 8522238
TI  - [A test for sperm cell survival in peritoneal fluid].
AB  - The role of the peritoneal fluid in the physiology of reproduction, as well as in
      the transportation and survival of gametes, is little known. The authors have
      examined interactions between spermatozoa and the peritoneal fluid, collected
      during laparoscopy in the, so-called, survival test, from 42 infertile couples.
      The studied survival of spermatozoa in the peritoneal fluid was relatively high-
      19% after 48 hours--longer than in Menezo B2 fluid. Values of the test have been
      indicated, especially in cases of endometriosis-caused and idiopathic
      infertility.

PMID- 8522239
TI  - [Use of fibrin glue in surgical treatment of urinary incontinence in women].

PMID- 8522240
TI  - [The respiratory system in pregnancy].
AB  - A survey throughout world literary output concerning physiology of respiratory
      system in pregnancy was made in this work. Metabolical changes caused by the
      increase of progesterone and other substances concentration and changes of the
      mechanics of ventilation connected by diaphragm raising caused by the growing
      uterus was discussed.

PMID- 8522241
TI  - [Retinoids--drugs with a strong teratogenic side effect].
AB  - The derivatives of the vitamin A--retinoids, are very precious drugs used in
      dermatology. Forever, they are very strong teratogens and their applications in
      case of women before the menopause may cause serious deformations of the fetus.
      So we presented the recommendations so as to applications of the retinoids in
      such women.

PMID- 8522242
TI  - [Roxithromycin (Rulid) in treatment of Chlamydia trachomatis genital infections
      in women].
AB  - New macrolide antibiotic, roxithromycin (erythromycin--like group), was tested in
      treatment of chlamydial genital infection in women. In comparison with
      doxycycline, roxithromycin showed higher clinical efficiency with fewer sides
      effects.

PMID- 8522243
TI  - [Video-laparoscopic removal of uterine myoma].

PMID- 8522244
TI  - [Uterine myoma complicated by cavernous lymphatic angioma of the liver].
AB  - In the article we present the case of fibroids complicated by a tumor derived
      from the left subcostal area and reached the corpus of uterus. The unquestionable
      diagnosis of tumor character and its origin could not be stated. Impossibility of
      laparoscopic examination caused decision of laparotomy. The tumor derived from
      the left liver lobe with dimensions of 26-31-11 cm and weight of 3.76 kg was
      discovered. The whole tumor was removed. Hist-path, evaluation of the tumor was:
      liver cavernosus angioma. The whole uterus with adnexa was removed.

PMID- 8522245
TI  - [Eventration of the small intestine through the vagina].
AB  - The paper is a description of prolapse of small intestine through vagina in 66
      year old woman, who had hysterectomy by laparotomy four years earlier. The
      intestines were repositioned by the vaginal route and then the opening at the top
      of vagina was sutured by laparatomy. In the next stage colpo-perineoplasty with
      formation of very high perineum was made.

PMID- 8522246
TI  - Where are we now and where are we going?

PMID- 8522247
TI  - The odyssey of a gynecologic oncologist.

PMID- 8522248
TI  - DNA amplification of HER-2/neu and INT-2 oncogenes in epithelial ovarian cancer.
AB  - OBJECTIVE: Oncogene alterations are thought to be prognostic indices in patients
      with breast cancer. The present study was carried out to investigate the
      amplification of the HER-2/neu and INT-2 oncogenes in ovarian cancer. METHODS: In
      a retrospective study of 196 patients with epithelial ovarian cancer, the
      amplification of the oncogenes HER-2/neu and INT-2 in the DNA of paraffin
      embedded tumor cells was determined by quantitative PCR. The purpose of this
      study was to analyze whether the two oncogenes correlated with such predictive
      factors as FIGO stage, histological grade, ascites, postoperative residual tumor
      mass, hormone receptor content, and preoperative CA 125 serum levels. The effect
      of HER-2/neu and INT-2 amplification on patient survival was also studied.
      RESULTS: The only correlation found in this study was between INT-2 and
      preoperative CA 125 levels (P = 0.03). No correlations were demonstrable between
      HER-2/neu (log-rank test; P = 0.67) and INT-2 (log-rank test; P = 0.75)
      amplifications and overall survival. CONCLUSION: Unlike the established
      prognostic factors, neither HER-2/neu nor INT-2 appears to be predictive for
      survival in patients with ovarian cancer.

PMID- 8522249
TI  - Intra-arterial chemotherapy with cisplatin followed by radical radiotherapy for
      locally advanced cervical cancer.
AB  - Locally advanced cervical cancer has a dismal prognosis, with a high local
      failure rate and a poor survival rate. To improve the cure rate for advanced
      carcinoma of the cervix, we initiated a study of intra-arterial (I-A)
      chemotherapy with cisplatin via the uterine artery prior to definitive
      radiotherapy. I-A chemotherapy via the internal iliac artery has been used to
      treat advanced cervical cancer; however, access by way of the uterine artery has
      not been tested for this purpose. Thirty-four patients with central tumor > or =
      5 cm in anteroposterior diameter observed on CT scans were treated with I-A
      chemotherapy. I-A chemotherapy consisted of unilateral catheterization of the
      uterine artery using 120 mg/m2 cisplatin. After assessment of I-A chemotherapy,
      all but 3 patients were treated with a combination of whole-pelvis external
      irradiation and intracavitary irradiation. The 3 patients underwent external
      radiotherapy alone. Twenty-seven of 34 patients treated were evaluable for
      response to I-A chemotherapy. Eleven patients (41%) experienced a partial
      response. Seventy-six percent of the 34 patients treated with I-A chemotherapy
      followed by radiotherapy exhibited a complete response by the end of treatment.
      Toxicity was well tolerated and no death due to treatment occurred. The 2- and 5
      year actuarial survival rates were 64 and 55%, respectively. The crude incidences
      of pelvic recurrence and distant metastasis observed at a median follow-up of 54
      months were both 47%. This study for locally advanced cervical cancer suggests
      there is benefit to be derived from our I-A chemotherapy followed by radical
      radiotherapy.

PMID- 8522250
TI  - Retroperitoneal leiomyosarcoma: eight cases and a literature review.
AB  - Leiomyosarcoma, a rare malignancy of smooth muscle, may arise from the
      retroperitoneum and present with the same vague symptoms as a malignancy of the
      pelvic organs. The purpose of this paper is to review eight cases of
      retroperitoneal leiomyosarcoma and to illustrate the presenting symptoms,
      prognostic indicators, and outcomes of patients seen at Indiana University
      Medical Center between 1989 and 1994. Patients in this study were white females
      who presented between the ages of 46 and 73 (mean age of 61.4) with nonspecific
      presenting symptoms of weight loss and back pain (37.5% for each). Tumor size
      (mean diameter of 14.6 cm in the range 4 to 35 cm), tumor extension, and the
      presence of distant metastases were of greater prognostic significance than tumor
      grade (7/8 were grade II, 1/8 was grade I). Surgical resection improved long-term
      prognosis; three of five patients undergoing resection are alive with no evidence
      of disease compared to zero of three treated nonsurgically. Due to location and
      vague presenting symptoms, this tumor continues to have a bleak prognosis and
      further evaluation and innovative treatment are required before a reasonable cure
      rate may be expected.

PMID- 8522251
TI  - Pelvic exenteration for malignant melanomas of the vagina or urethra with over 3
      mm of invasion.
AB  - Pelvic exenteration has usually been employed as salvage treatment for
      gynecologic malignancies which have failed primary radiotherapy. The therapeutic
      mainstay for vulvar melanomas has become wide local excision with or without
      concurrent regional node dissection. Patients with primary melanoma of the vagina
      who undergo exenteration as primary therapy may experience 50% 5-year survival if
      the pelvic nodes are free of metastases. However, the overall 5-year survival for
      vaginal melanoma is 15%. In our patient population, there have been four patients
      with vaginal or urethral melanomas treated primarily with pelvic exenteration.
      The purpose of this study was to report that patients with vaginal or urethral
      melanomas over 3 mm in thickness may benefit from primary pelvic exenteration.
      Four patients underwent pelvic exenteration at Indiana University Medical Center
      for malignant melanoma of the vagina or urethra between 1986 and 1992. The
      pathologic specimens of all patients were analyzed for thickness, growth pattern,
      and nodal metastases. Patient age ranged from 50 to 71. Thickness of the
      melanomas ranged from > 3 to 12 mm. All four patients underwent exenterations,
      three total and one anterior. All patients had negative pelvic and inguinal nodes
      at the time of surgery. None of the patients has experienced a recurrence. Three
      of four patients are alive without evidence of disease at 31 to 97 months
      following their exenteration. One patient died postoperatively of cardiopulmonary
      complications. Patients with melanomas of the vagina and female urethra, greater
      than 3 mm in thickness, may benefit from primary pelvic exenteration.

PMID- 8522252
TI  - Uterine sarcoma: a report of 10 cases studied by transvaginal color and pulsed
      Doppler sonography.
AB  - OBJECTIVE: To evaluate the role of transvaginal color Doppler in differentiating
      uterine sarcoma from myoma. STUDY DESIGN: A group of 2010 women were examined by
      transvaginal color Doppler ultrasonography 1 day before planned hysterectomy. Ten
      cases with uterine sarcoma were analyzed with respect to their color Doppler
      sonographic patterns and compared with 150 normal and 1850 myomatous uteri.
      Analysis of variance was used to test the significance among the subgroups.
      RESULTS: All cases of uterine sarcoma (100%) revealed abnormal tumoral blood
      vessels. The mean resistance index (RI) of these vessels was 0.37 +/- 0.03,
      ranging from 0.32 to 0.42, which is statistically significantly lower than that
      of the normal and myomatous (P < 0.001) uteri. There was no significant
      difference between RI in the right and left uterine arteries in each separate
      group; however, there was a decline in these values from normal, through
      myomatous, to sarcomatous uteri. Using a cutoff point of 0.40 for RI we were able
      to distinguish between benign and malignant myometrial tumors with a sensitivity
      of 90.91%, specificity of 99.82%, positive predictive value of 71.43%, and
      negative predictive value of 99.96%. CONCLUSION: Color Doppler sonography has the
      potential to distinguish uterine sarcoma from benign uterine lesions.

PMID- 8522253
TI  - Progesterone receptor levels independently predict survival in endometrial
      adenocarcinoma.
AB  - Estrogen receptor (ER) and progesterone receptor (PR) contents were determined by
      biochemical (dextran charcoal-coated (DCC) assay) and immunohistochemical (ICA)
      methods in biopsies from 145 primary endometrial adenocarcinomas and those with
      eligible receptor measurements were analyzed with respect to correlations to
      cancer-specific survival in a multivariate analysis including histopathological
      characteristics. Median patient follow-up time was 67 months with 18 cancer
      deaths. The PR-DCC and ER-DCC values were dichotomized according to levels
      previously found by us to correspond to the best agreement between receptor
      status as determined by the DCC and ICA methods (130 fmol/mg cytosol protein for
      ER, 114 fmol/mg for PR). Using these thresholds, we found by multivariate
      analysis that "high" PR-DCC levels (> 114 fmol/mg) correlated significantly (P =
      0.004) with survival, independent of stage risk group (Ia + b vs Ic-IV). Patient
      age and histologic grade were prognostic factors in a univariate setting, but
      these parameters were eliminated in the multivariate model. While the PR-ICA
      scores also correlated significantly and independently with survival, the
      predictive effect of PR-ICA positivity alone could not be statistically evaluated
      due to the number of cases with eligible ICA values. However, we suggest that
      owing to a close correlation between DCC and ICA results, PR-ICA status may
      provide significant prognostic information when DCC measurements are not
      available.

PMID- 8522254
TI  - Female urethral adenocarcinoma: evidence for more than one tissue of origin?
AB  - Adenocarcinoma of the female urethra accounts for 10% of all urethral cancers.
      Controversy continues to exist over the origin of primary urethral
      adenocarcinomas. The periurethral (Skene's) glands appear to be the homologues of
      the male prostate as defined by authors evaluating cadaver-derived periurethral
      glands pathologically and immunohistochemically (prostate-specific antigen
      (PSA)). It is traditionally assumed that the origin of female urethral
      adenocarcinoma is the Skene's gland. However, no one has evaluated a series of
      primary urethral adenocarcinomas in an effort to scrutinize this assumption. We,
      therefore, evaluated 13 primary adenocarcinomas of the female urethra comparing
      histologic and immunohistochemical characteristics. Tumors were classified into
      two major histologic groups: columnar/mucinous (11) and clear cell (2). Excluding
      one case, the columnar/mucinous tumors resembled either endometrial or colonic
      adenocarcinoma. The exception was a case bearing a striking resemblance to
      prostatic adenocarcinoma. Immunohistochemical results revealed positive PSA
      staining for this tumor alone. The patient's preoperative serum PSA was elevated,
      but rapidly declined postoperatively. Based on immunohistochemical findings and
      the presence of distinct histologic subtypes (columnar/mucinous, clear cell), it
      appears that female urethral adenocarcinoma has more than one tissue of origin
      with a minority arising from the Skene's glands.

PMID- 8522255
TI  - Nonsurgical management strategies for the functional complications of ileocolonic
      continent urinary reservoirs.
AB  - Urinary diversion with creation of a continent ileocolonic reservoir was
      performed in 25 patients with gynecological malignancies at our institution
      between September 1989 and September 1994. A retrospective review was conducted
      and cases were analyzed for functional complications associated with reservoir
      formation. Functional reservoir complications were defined as (1) difficulty with
      catheterization, (2) reservoir fistulae, (3) reservoir stones, and (4) ureteral
      stenosis. Management strategies and outcomes for these complications were
      determined. All patients had received prior pelvic radiation therapy. There was
      no surgical mortality. Median follow-up was 21 months, and 16 patients (64%) are
      currently alive. Fourteen of the patients (56%) had one or more complications
      attributable to a functional aspect of the continent reservoir. Two patients had
      difficulty with catheterization (8%), two patients had reservoir leak (8%), and
      one patient had reservoir stones (4%). Nonsurgical management strategies were
      used in these cases including balloon dilation of the ileocecal valve, stomal
      dilation, ureteral stenting, percutaneous nephrostomy, and endoscopic
      lithotripsy. All cases of catheterization problems, reservoir fistulae, and
      reservoir stones were resolved with nonoperative techniques. Thirteen of 50
      ureters (26%) had some degree of stenosis. Percutaneous balloon dilation was
      utilized in nine cases of ureteral stenosis. Relief of stenosis was complete in
      five, partial in two, and not achieved in two of the cases. No patients required
      a reoperation for a reservoir complication. In conclusion, continent ileocolonic
      urinary diversion can be performed in patients previously treated with
      radiotherapy; however, functional reservoir problems may occur. Interventional
      radiology strategies are useful in managing many of these problems and
      reexploration can be successfully avoided.

PMID- 8522256
TI  - CD4 lymphocytes in women with invasive and preinvasive cervical neoplasia.
AB  - OBJECTIVE: To assess the relationship between CD4 lymphocyte population and stage
      of disease in cervical neoplasia. METHODS: Study population was 107 women with
      invasive cervical cancer, 116 women with cervical intraepithelial neoplasia
      (CIN), and 32 women without neoplasia diagnosed in 1988-1994. All women under age
      50 were seronegative for the human immunodeficiency virus (HIV). All women over
      age 50 with CD4:CD8 ratio below normal were HIV-negative. Stage was defined by
      FIGO criteria using clinical findings. CD4 and CD8 lymphocyte populations were
      enumerated by flow cytometry prior to treatment. The normal range of CD4 counts
      was defined as 537-1571 cells/mm3. RESULTS: Distribution of CD4 count was similar
      in stages I (n = 40), II (n = 24), and III (n = 32), with 31% below normal and 9%
      above normal (mean CD4 count = 881). However, in stage IV (n = 11), 64% were
      below normal and 18% above normal (mean CD4 = 591). The difference in
      distribution between stages I-III and stage IV was statistically significant.
      Among 116 CIN patients, 10% had CD4 counts below normal and 3% above normal (mean
      CD4 = 910). Among 32 women without cervical neoplasia, 0% had CD4 counts below
      normal and 3% above normal. The difference between CIN and invasive cancer in the
      distribution of CD4 counts and CD8 counts was significant (P < 0.01). There was
      no difference in the CD4 count distribution by CIN severity. Forty-five percent
      of patients with below-normal CD4 counts at diagnosis developed recurrent cancer
      compared to 43% of patients with normal or above-normal CD4 counts. CONCLUSION:
      Women with invasive cervical cancer have lower CD4 counts and a broader
      distribution compared to women with preinvasive or no neoplasia. Metastatic
      cancer at diagnosis was associated with severely depressed CD4 count.

PMID- 8522257
TI  - High-dose-rate brachytherapy as the primary treatment of medically inoperable
      stage I-II endometrial carcinoma.
AB  - Between 1984 and 1992, 27 patients with clinical stage I-II histologically proven
      adenocarcinoma of the endometrium who had significant medical risks precluding
      surgery underwent radiotherapy (RT) as the primary treatment. The median age at
      diagnosis was 74 years. There were 20 patients (74%) with stage I and 7 patients
      (26%) with stage II disease. Patients were treated with high-dose-rate
      brachytherapy (HDRB) alone (19/27) or with a combination of external-beam RT and
      HDRB (2 stage I; 6 stage II). HDRB was delivered using a cobalt-60 HDR remote
      afterloading unit, with a median dose of 2000 cGy to point A, in two to three
      fractions given once a week. All HDRB treatments were performed under spinal
      anesthesia on an outpatient basis. External-beam irradiation to the pelvis was
      given using 4- to 6-MV photons and a median dose of 4200 cGy was delivered. In
      all patients, vaginal bleeding was controlled within a few days after completion
      of RT. With a median follow-up of 47 months, the 8-year disease-specific survival
      rate was 76%. Patients with stage I had an 8-year survival rate superior to that
      of patients with stage II (95% vs 21%, P < 0.001). No complications were
      experienced during HDRB. Late serious complications were seen in 3 patients
      (11%). Based on this retrospective review, primary RT with HDRB appears to be an
      effective and safe treatment for those patients with medically inoperable
      clinical stage I endometrial carcinoma. Because HDRB is given on an outpatient
      basis, it is an attractive option for these patients. However, in stage II
      disease the results of treatment are poor and RT alone should be considered only
      when the surgical risks are too high.

PMID- 8522258
TI  - Use of ileocecal continent urinary reservoir in patients with previous pelvic
      irradiation.
AB  - OBJECTIVE: To assess the results of the use of ileocecal continent urinary
      reservoirs in patients with previous pelvic irradiation. METHODS: A retrospective
      analysis for morbidity and clinical outcome was undertaken for 37 female patients
      with prior therapeutic pelvic irradiation who underwent continent urinary
      diversion with a detubularized right colonic segment as the urinary reservoir, a
      plicated ileocecal valve as the continence mechanism, and a tapered distal ileum
      for efferent catheterization. RESULTS: Thirty-one patients had persistent or
      recurrent pelvic malignancies, 17 of whom had total pelvic exenteration and 14
      had anterior exenteration. The remaining 6 patients had radiation-induced
      vesicovaginal fistulas without evidence of recurrence and underwent urinary
      diversion alone. Follow-up ranged from 2 to 33 months (median 11 months).
      Postoperative radiographic evaluation revealed no evidence of urinary
      extravasation. Of the 74 implanted ureters, 4 had reflux (5%), 2 developed
      stricture (3%), and 5 had mild to moderate hydronephrosis (7%). All patients
      achieved daytime continence with catheterization intervals of 3-8 hr (median 4
      hr) and capacities of 200-1000 cc (median 500 cc). Nighttime continence was
      reported by 33 of 37 patients (89%). Reoperation was required in 3 patients (8%),
      2 with stoma stenosis and 1 with difficulty in catheterization. CONCLUSIONS: The
      use of the ileocecal continent urinary reservoir in patients with previous pelvic
      irradiation achieves results comparable to those reported for nonirradiated
      patients, thus supporting its use in this select group of patients.

PMID- 8522259
TI  - Expression of retinoblastoma tumor suppressor gene protein, epidermal growth
      factor receptor, and c-erbB-2 oncoprotein in primary vaginal carcinomas.
AB  - Forty-six primary vaginal carcinomas were examined immunohistochemically for
      expression of retinoblastoma (RB) protein, epidermal growth factor receptor
      (EGFR), and c-erbB-2 oncoprotein. The results demonstrated that RB protein was
      not lost in any of the cases, suggesting that structural abnormalities of the RB
      gene may not play an important role in the pathogenesis of vaginal carcinoma.
      Fifteen and 11% of the cases showed increased expression of EGFR and c-erbB-2
      oncoprotein, respectively, indicating that these oncoproteins may be involved in
      the neoplastic process of a minority of vaginal carcinomas. Overexpression of
      EGFR and c-erbB-2 oncoprotein had no prognostic significance in vaginal
      carcinomas.

PMID- 8522260
TI  - Uterine papillary serous carcinoma (UPSC): a clinicopathologic study of 30 cases.
AB  - Between 1975 and 1989, 896 patients were treated for endometrial carcinoma at the
      Massachusetts General Hospital. Thirty patients were identified from the tumor
      registry as having uterine papillary serous carcinomas. The survival for all
      patients and for groups of patients stratified on clinical and pathological
      parameters was examined in the Kaplan-Meier survival curves. Curves for the
      different strata were compared using the logrank test. The 5-year survival for
      the 30 patients was 30% +/- 9%. Patients with surgical stage I and II tumors had
      a 5-year survival rate of 79% +/- 14% compared to 25% +/- 10% in patients with
      stage III and IV tumors (P = 0.02). Clinical stage, depth of myometrial invasion,
      lymph-vascular space invasion, tumor grade, and DNA aneuploidy were not found to
      significantly impact on survival. However, a survival advantage was seen in
      patients diagnosed with early surgical stage tumors, reinforcing the need for
      thorough staging at the time of laparotomy.

PMID- 8522261
TI  - Platinum-based chemotherapy for advanced-stage serous ovarian carcinoma of low
      malignant potential.
AB  - PURPOSE: To evaluate the effect of platinum-based chemotherapy on tumor response
      in patients with advanced-stage serous ovarian carcinoma of low malignant
      potential. PATIENTS AND METHODS: We conducted a retrospective review of hospital
      records, pathology slides, and office charts of patients identified as having
      Stage III or IV serous ovarian cancer of low malignant potential. RESULTS:
      Between November 1979 and April 1993, 21 patients with advanced-stage serous
      ovarian carcinoma of low malignant potential received platinum-based chemotherapy
      following initial cytoreductive surgery. The amount of residual disease was
      recorded in 20 patients; 8 (40%) had macroscopic residual tumor < 2 cm in largest
      diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a
      second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of
      disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%)
      had progressive disease. During a mean follow-up of 64 months, only 1 patient had
      died of disease. She had progressive disease noted at second-look laparotomy.
      Five of 6 patients who did not have a complete response to initial chemotherapy
      underwent further therapy with oral etoposide (1), intraperitoneal platinum (2),
      intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no
      further therapy. Three of the patients subsequently receiving salvage
      intraperitoneal therapy underwent a third-look laparotomy. Two had partial
      responses noted, while the third patient had stable disease. CONCLUSIONS:
      Platinum-based chemotherapy is effective in achieving surgically documented
      responses in patients with advanced-stage serous ovarian tumors of low malignant
      potential. The benefit of this therapy in improving survival is unproven.

PMID- 8522262
TI  - Possible metaplastic origin of lymph node "metastases" in serous ovarian tumor of
      low malignant potential (borderline serous tumor).
AB  - A patient with a stage III serous ovarian carcinoma of low malignant potential
      (borderline serous tumor) is described who had extensive involvement of the
      pelvic and para-aortic lymph nodes by both borderline tumor and endosalpingiosis.
      Transition from endosalpingiosis to papillary serous borderline tumor was
      demonstrable in multiple intranodal sites, and in fully developed lesions, areas
      of metaplastic growth acquired a desmoplastic stroma. This finding suggests that
      the lymph node "metastases" may have arisen de novo by neoplastic transformation
      of preexistent metaplastic tubal-type epithelium (endosalpingiosis), and would
      lend further credence to the metaplastic (rather than metastatic) origin or
      extraovarian implants in serous ovarian carcinoma of low malignant potential.

PMID- 8522263
TI  - Successful pregnancy in a patient with pseudomyxoma peritonei arising from
      ovarian mucinous cystadenocarcinoma treated with cisplatin.
AB  - A 24-year-old Japanese woman clinically showing pseudomyxoma peritonei arising
      from ovarian mucinous cystadenocarcinoma FIGO stage Ic is reported. She received
      intra-abdominal administrations of cisplatin five times following left
      oophorectomy. After being free of disease for 6 months, she conceived and carried
      two pregnancies to successful deliveries at 34 and 37 weeks, respectively. At the
      Cesarean sections, there were no abnormal findings except for right ovarian
      mucinous cystadenoma. She has had no evidence of recurrence by the time of the 60
      month postoperative examination.

PMID- 8522264
TI  - The use of operative laparoscopy in determining eligibility for pelvic
      exenteration in patients with recurrent cervical cancer.
AB  - In patients with suspected recurrent cervical cancer after radiation therapy, it
      can be very difficult to pathologically confirm recurrence and clinically
      determine if tumor is resectable via a curative pelvic exenteration. Despite very
      thorough preoperative investigation uncertainties often remain, so patients
      ultimately undergo exploratory laparotomy. Unfortunately, inoperable disease is
      frequently discovered then. We report the use of operative laparoscopy in three
      patients with recurrent stage IIIB cervical cancer. The age ranged from 38 to 79
      years. The mean duration of the procedure was 146 min (range 110-180 min) and
      blood loss was minimal. The procedure was well tolerated in all patients. There
      was no intraoperative complication but one deep thrombophlebitis occurred
      postoperatively. The procedure was successful in all cases in confirming
      recurrence and selecting out patients who were not surgical candidates for pelvic
      exenterations. Operative laparoscopy is a less invasive procedure that may be a
      valuable step in the workup of patients with recurrent cervical cancer. With
      experience in retroperitoneal surgery, the procedure can be carried out safely.
      We believe that this approach could prevent unnecessary laparotomies, shorten the
      hospital stay and the postoperative recovery, and contribute to a better quality
      of life for women with inoperable disease.

PMID- 8522265
TI  - Meigs' syndrome with elevated serum CA 125 levels: two case reports and review of
      the literature.
AB  - Two cases of Meigs' syndrome in association with elevated serum CA 125 levels are
      reported. The significance of Meigs' syndrome lies in the fact that neither
      ascites nor pleural effusion is necessarily an ominous sign in women with a
      pelvic tumor. Although there is a strong correlation between ovarian malignancy
      and elevated serum CA 125 levels, several benign conditions have been found to
      cause a rise in CA 125 levels. It is important to remember that a pelvic neoplasm
      in a woman presenting with hydrothorax, ascites, and elevated CA 125 levels might
      be benign and that this condition can rapidly be resolved with surgical removal.
      Neither ultrasound examination nor computed tomography can reliably offer a
      preoperative diagnosis.

PMID- 8522266
TI  - A case of unsuspected endometrial stromal sarcoma removed by operative
      hysteroscopy.
AB  - A 26-year-old woman underwent operative hysteroscopy to remove a polypoid lesion,
      responsible for recurrent abnormal uterine bleeding. The polypoid mass was 4 cm
      long, smooth, with dilated vessels. It had a large base and originated from the
      fundum and posterior wall of the uterus. Pathological examination of the resected
      specimen showed low-grade stromal sarcoma. The patient subsequently underwent a
      total abdominal hysterectomy and bilateral salpingo-oophorectomy. No tumor
      residual was found in the surgical specimen. As diagnosis of stromal sarcoma is
      too difficult to be made preoperatively, the complete resection of all
      intracavitary lesions and the pathology of all tissue specimens are suggested.

PMID- 8522267
TI  - Two unusual presentations of mullerian adenosarcoma: case reports, literature
      review, and treatment considerations.
AB  - Mullerian adenosarcomas of the uterus usually present as pedunculated endometrial
      masses in postmenopausal women with vaginal bleeding. Extraendometrial variants
      (originating in the ovary, adnexa, or myometrium) are much less common, and they
      tend to present at a more advanced stage due to their location. The sarcomatous
      portion of mullerian adenosarcoma can vary from low grade to very high grade and
      the clinical behavior of the tumors can be indolent or aggressive. We present two
      cases, one of which originated in the adnexa and the other in an apparent focus
      of uterine adenomyosis. These cases illustrate the difficulty of correct
      diagnosis and treatment.

PMID- 8522268
TI  - Uterine cervix adenocarcinoma with both human papillomavirus type 18 and tumor
      suppressor gene p53 mutation from a woman having an intact hymen.
AB  - Human papillomavirus (HPV) type 18 DNA was found in an aggressively invasive
      adenocarcinoma tumor from a woman who had an intact hymen and denied any prior
      sexual intercourse. The viral DNA was detected within the tumor tissue by
      polymerase chain reaction (PCR) using consensus primers for the L1 region of
      oncogenic high-risk genital HPVs. In order to determine mutations within the
      tumor suppressor gene p53, the gene exons were amplified by PCR followed by
      single-stranded conformation polymorphism (SSCP) analysis. The appearance of a
      mutation in exon 8 of the p53 gene suggested by SSCP was directly confirmed by
      DNA sequencing of the exon. The sequencing showed a single base deletion that may
      truncate the protein by introducing a early stop codon in the messenger RNA. This
      early truncation could be expected to affect the proper oligomerization of the
      p53 protein and hence its DNA-binding activity. The results show that genital
      oncogenic human papillomaviruses may be passed by nonsexual routes and suggest
      that the virus may work in concert with p53 mutations to help the infected tissue
      progress toward invasive cancer.

PMID- 8522269
TI  - Malignant degeneration of a mature cystic teratoma five decades after discovery.
AB  - Malignant degeneration of mature cystic teratomas has been reported in 1-3% of
      cases. A patient with the unusual occurrence of a stage IIIC squamous cell
      carcinoma arising in a mature teratoma over 50 years after initial diagnosis is
      presented. The patient was treated with pelvic radiotherapy. The role of serum
      squamous cell carcinoma antigen in detecting degeneration of mature cystic
      teratomas at an early stage is considered.

PMID- 8522270
TI  - Chromosomal locations of major tRNA gene clusters of Xenopus laevis.
AB  - In Xenopus laevis eight tRNA genes are located in a 3.18 kb tandemly repeated
      unit. There are 150 copies of the unit at a single locus near the long arm
      telomere of one of the acrocentric chromosomes in the 14-17 group. Two additional
      classes of tRNA gene-containing repeats have been isolated (defined by clones
      p3.1 and p3.2) that have structures related to that of the 3.18 kb unit. Using in
      situ hybridization at the electron microscopic level, the p3.2 repeats are found
      clustered at a single locus in the subtelomeric region on one of the
      submetacentric chromosomes, whereas the p3.1 repeats are clustered at a locus
      indistinguishable from that containing the 3.18 kb repeats. This suggests that
      these tDNA tandem repeats can diverge in sequence from each other without being
      at distantly separated loci.

PMID- 8522271
TI  - [Biosynthetic mechanism of endothelins with various physiological and
      physiopathological significance--structure and function of endothelin converting
      enzyme].

PMID- 8522272
TI  - A progressive occlusion of the internal carotid arteries in a case of adult-onset
      moyamoya disease.
AB  - Progressive occlusions of the intracranial portions of ICAs are already
      established phenomena in childhood-onset moyamoya disease, but they have not yet
      been demonstrated in adult-onset patients. A patient with moyamoya disease
      manifested at 25 years of age was examined with cerebral angiography at 27 and 45
      years of age. The angiograms taken at 27 revealed that the right ICA was
      completely occluded at the clinoidal portion, while the left one was patent and
      the occlusive/stenotic change was limited to the terminal portion. Angiograms
      taken 17 years later revealed that the right ICA was occluded at the origin,
      while the left one concentrically narrowed at the origin, then tapered off and
      was occluded at the clinoidal portion. The present case suggests that the ICA
      occlusion of moyamoya disease is not limited to the intracranial segment but
      progresses to the cervical segments, even in adult-onset patients. Based on these
      findings, two different groups of adult-onset moyamoya disease may exist; one in
      which the occlusive disorder has been completed by the time clinical
      manifestations appear and thereafter decreases, while the other group consists of
      occlusive disorders that steadily progress to the original portion of ICA.

PMID- 8522273
TI  - [Psychiatric symptoms following accidental exposure to sarin--a case report].
AB  - A middle aged man who inhaled sarin in a train in a subway station in Tokyo in
      1995 and showed a variety of symptoms including psychiatric symptoms was
      reported. He experienced muscle weakness, dyspnea and unconsciousness of sudden
      onset immediately after exposure to sarin. Marked miosis was observed on
      admission. Plasma cholinesterase activity was remarkably decreased at that time.
      He also experienced delirium consisting of visual hallucination, insomnia and
      irritability at mid-night for more than seven days. These psychiatric symptoms
      gradually improved without any medication. To date there is no detailed
      description of such psychiatric symptoms in sarin poisoning.

PMID- 8522274
TI  - Nocturnal urinary growth hormone excretion in growth hormone-deficient children
      on and off growth hormone treatment.
AB  - Non-compliance has been reported as a major issue in growth hormone (GH) therapy.
      We explored the use of urinary GH (uGH) measurements to monitor the GH treatment
      of 18 children (aged 5-16 years) diagnosed as GH deficient on the basis of
      history, phenotype, auxology and peak GH concentration during 2 provocation tests
      of < 15 mU/l. Each child collected 5 consecutive overnight urine samples while on
      GH replacement schedules, then discontinued treatment for 2 days and collected a
      further 5 urine samples. The mean mass of uGH excreted on treatment (8.6 ng,
      range 3.6-13.0 ng) was significantly greater than that off treatment (1.2 ng,
      range 0.6-2.7 np; p < 0.01). All uGH values on treatment exceeded the mean
      nocturnal uGH excretion of normal age- and sex-matched children. The clear
      distinction between uGH levels on and off GH treatment indicates that uGH
      measurement would determine whether two or more GH injections had been missed. A
      series of uGH estimates over a 2-week period may provide a realistic perspective
      on injection frequency.

PMID- 8522275
TI  - Spontaneous adult height in idiopathic short stature.
AB  - Two hundred and thirty-six patients with idiopathic short stature (ISS) (184 m,
      52 f) who presented at a mean age of 12.2 (range 2.8-17.5) years, a mean height
      of -2.16 standard deviation score (SDS), a mean target height (THT) of -0.27 SDS
      (m = f), were reinvestigated at a mean age of 20.5 (range 18-24) years. 182(142
      m, 37 f) (67%) had reached normal adult height (AHT) while 54 (39 m, 15 f) (23%)
      had not. However, only 23 (17 m, 6 f) did not reach a height within their
      familial target. Patients were subdivided into 2 groups according to deviation
      from familial height target: 60(44 m, 16 f) were considered adequate for their
      families (group 1), while 176 (140 m, 39 f) were smaller (group 2). Children in
      group 1 were younger and bone age (BA) was less retarded. Patients in group 1
      reached their THT, this was not the case in group 2. Young age, low THT and low
      predicted adult height (PAH) at presentation were the factors associated with
      poor stratural outcome, but AHT could not be predicted in individuals. In boys,
      PAH (Bayley-Pinneau) (0.0 SDS) exceeded AHT (-0.7 SDS), in girls, both were
      almost identical (-0.79, -0.77 SDS). Since most children with ISS reach an AHT
      within the normal range, attempts to improve AHT by means of growth-promoting
      therapies appear to be justified only in a minority of selected patients with
      ISS. Methods to improve the accuracy of individual height prognoses are needed.

PMID- 8522276
TI  - GH secretion in thalassemia patients with short stature.
AB  - The physiological role of GH secretion on growth retardation remains to be
      elucidated especially in patients with beta-thalassemia. In the present study, we
      investigated IGF-1 circulating levels as well as GH release following GHRH alone
      or combined with some inhibitors of somatostatin: pyridostigmine and arginine. In
      thalassemic patients lower IGF-1 circulating levels appear to be negatively
      correlated with both aspartate aminotransferase and alanine aminotransferase as
      well as with ferritin circulating levels indicating a probable role of hepatic
      hemosiderosis in IGF-1 production. The authors however suggest that reduced IGF-1
      secretion is not the main cause of growth retardation since this would have
      elicited an enhanced response of GHRH in the presence of a normal hypothalamic
      pituitary axis. In contrast, they noticed that GH response to GHRH when expressed
      as area under the curve was lower in thalassemic patients compared to controls.
      The combination of GHRH with either pyridostigmine or arginine induced a GH
      secretion in thalassemics which was comparable to that of controls. The results
      of this study lead to conclude that the alteration of GH secretion is due, in
      such patients, to an increased somatostatin activity.

PMID- 8522277
TI  - Growth hormone treatment in Noonan syndrome: report of four cases who reached
      final height.
AB  - Final height of 4 patients with Noonan syndrome and short stature treated with
      growth hormone (GH) is reported. Four prepubertal girls (chronological age 12.3
      15.1 years, bone age 11.0-11.5 years) were treated with recombinant human growth
      hormone (0.5 IU/kg/week s.c.) for at least 3 years. Stimulated GH secretion was
      normal, spontaneous nocturnal GH secretion was low in 1 patient. Final height, as
      standard deviation score according to Ranke-specific standards for Noonan
      syndrome, improved in 3 patients and 2 of the exceeded their corrected
      midparental height.

PMID- 8522278
TI  - Bone mineral density of prepubertal age girls with Turner's syndrome while on
      growth hormone therapy.
AB  - Bone mineral densities and growth velocities of young girls with Turner's
      syndrome treated with recombinant human growth hormone at an age before the
      decreased levels of estrogens secondary to their ovarian failure could contribute
      to osteopenia were studied. Twelve patients with a mean chronological age of 8.9
      +/- 0.9 years and a mean bone age of 6.9 +/- 0.8 years received growth hormone
      therapy for over 2 years (0.5 IU/kg/week s.c.) Mean growth velocities increased
      significantly from a baseline level of 3.5 +/- 0.4 cm/year to 6.4 +/- 0.3 and 5.7
      +/- 0.4 cm/year at 12 and 24 months of therapy, while height SDS improved from 
      3.1 +/- 0.4 at baseline to -2.7 +/- 0.3 and -2.4 +/- 0.3 at 12 and 24 months,
      respectively. Total bone calcium as well as cortical bone mineral density of our
      density of our patients while on recombinant human growth hormone were similar to
      that of a control group of prepubertal healthy growth children paired for bone
      age and height; bone density of trabecular bone was however increased in our
      patients when compared to healthy controls (0.791 +/- 0.04 vs. 0.669 +/- 0.02
      g/cm2; p < 0.025). We conclude from our study that the bone mineral status of
      young girls with Turner's syndrome on growth hormone therapy seems to be normal.

PMID- 8522279
TI  - Final height in Turner syndrome patients treated with growth hormone.
AB  - The first treatment trials on patients presenting with Turner syndrome were
      successful in accelerating growth velocity. It is therefore essential to know the
      final height of the patients who were treated in order to ascertain whether or
      not growth hormone treatment increases final height. We are reporting on a group
      of 117 patients with Turner syndrome whose growth hormone treatment was initiated
      in 1986. The mean growth hormone dose was 0.74 IU/kg/week for an average period
      of 4 years. At the start of treatment, the patients' chronological age was 129/12
      years, height -3.8 +/- 1.0 standard deviation scores (SDS) and bone age 10.5 +/-
      2.1 years. Mean final height was 147.7 +/- 5.6 cm, i.e. a gain of 1.5 SDS. We
      noted no significant difference due to the type of chromosomal abnormality, nor
      to oxandrolone or estrogen-associated treatment. A significant correlation was
      found between final height, mean parental height, the duration of the treatment,
      height SDS at the start of treatment and growth hormone peak during
      pharmacological stimulation tests. However, there was no correlation between
      growth hormone dosage, chronological age and bone age at the start of treatment.
      These results show that the growth hormone treatment improves the final heights
      of patients with Turner syndrome.

PMID- 8522280
TI  - Nutritional status and growth hormone-binding protein.
AB  - To study the effects of nutrition on growth hormone (GH) receptor status, the
      plasma GH-binding protein was evaluated under conditions of poor nutrition,
      anorexia nervosa, celiac disease, and obesity. Nine patients, aged 12-30 years,
      presented anorexia nervosa and had a mean weight loss of -19% of their initial
      weight at the time of the study. Ten patients with celiac disease, aged 3-14
      years, had a mean height at -4.2 SD, and normal body weight for height. Fourteen
      severely obese children, aged 3-10 years, had a mean body mass index (BMI) of
      25.7 +/- 0.9. GH-binding protein was low in patients with anorexia nervosa (16.8
      +/- 1.9% of radioactivity) and in patients with celiac disease (16.1 +/- 2.2%)
      whereas it was very high in obese children (57.2 +/- 3.3%). A strong correlation
      was found between GH-binding protein and BMI. GH-binding protein was also
      correlated with insulin-like growth factor-1 plasma levels. Nutrition is an
      important regulator of the GH receptor/binding protein. The growth failure
      presented by undernourished children is associated with partial GH resistance and
      low GH receptor level. On the contrary, children with obesity and normal growth
      have a high GH receptor level.

PMID- 8522281
TI  - Heterogeneity of urinary steroid profiles in children with adrenocortical tumors.
AB  - The excretory patterns of urinary steroids determined by capillary gas
      chromatography in 11 children (aged 0.8-16.5 years) with adrenocortical tumors
      were established. In 8 patients the predominant clinical feature was
      virilization, in 3 others, Cushing's syndrome. In 5 patients (3 carcinoma, 2
      adenoma) very high excretion of 3 beta-hydroxy-5-ene steroids was observed. In 2
      others (adenomas) only moderately elevated excretion of 11 beta
      hydroxyandrosterone was found. In 1 patient (adenoma) pregnanediol dominated in
      the steroid profile, accompanied by moderately elevated 3 beta-hydroxy-5-ene
      steroids. Out of 3 Cushingoid patients (1 carcinoma, 2 adenomas), 1 presented an
      atypical urinary steroid pattern for hypercortisolemia, without 5 alpha-reductase
      and 11 beta-hydroxysteroid dehydrogenase deficiencies. Neither the urinary
      steroid pattern nor tumor size alone were reliable indicators of tumor
      malignancy, as evaluated by a pathological examination and subsequent metastasis
      free survival.

PMID- 8522282
TI  - Total fibrin and fibrinogen degradation products in urine: a possible probe to
      detect illicit users of the physical-performance enhancer erythropoietin?
AB  - Erythropoietin (Epo) represents for some athletes the ultimate tool to gain an
      edge over their peer competitors. Underground information indicates that its
      usage is spreading at an epidemic pace since no analytical technique is yet
      available to detect its utilization. We hereby report observations obtained from
      analysis of urine specimens collected from top-level athletes after international
      calibre competitions. Possible Epo misuse was evaluated by the measurement of
      urine total degradation products (TDPs), excretory fragments attributed by
      Sakakibara et al. to the fibrinolytic action of Epo. Markedly elevated urine TDP
      levels were measured in more than 13% of the 76 top-level athletes evaluated in
      this study. Analyses of urine specimens from a control hockey player group and
      from out-of-competition resting subjects indicate that the urine TDP content is
      not significantly influenced by exercise per se. Solid confirmation of TDP
      measurement as a sound probe to detect illicit Epo users should come from
      controlled studies with concomitant administration of Epo.

PMID- 8522283
TI  - Transient nephrogenic diabetes insipidus accompanied by possible psychogenic
      polydipsia.
AB  - A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2
      months without any other specific symptoms. His daily urinary output reached 5
      liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals,
      pituitary or hypothalamus were detected by laboratory tests and MRI of the head.
      Pure psychogenic polydipsia was ruled out because his urine volume did not
      decrease sufficiently with 18 h of water deprivation and the subsequent injection
      of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma
      osmolality remained within the normal range during the test. These results
      indicated that diabetes insipidus in this case was caused by renal insensitivity
      to AVP. The symptoms disappeared spontaneously, and marked improvement was
      observed in a second water deprivation test 1 month later, although the maximum
      urine concentration was still subnormal. The combination of both latent
      insufficiency of AVP secretion and impairment of the renal countercurrent system
      induced by psychogenic polydipsia was speculated as a possible mechanism for the
      transient nephrogenic diabetes insipidus in this case.

PMID- 8522284
TI  - Phyllodes tumours of the breast: a clinicopathological review of thirty-two
      cases.
AB  - We have reviewed the histological features and clinical outcome in 32 women with
      phyllodes tumours of the breast diagnosed in Nottingham between 1975 and 1990. We
      assessed 23 tumours as histologically benign, four as borderline and five as
      malignant. After clinical follow up for periods ranging from 36 months to 221
      months (median 135 months), six of 23 benign tumours have recurred locally; in
      all these cases the original tumours had been incompletely excised. There were no
      recurrences amongst 10 benign tumours in which excision had been complete. Benign
      tumours which recurred showed a tendency to greater stromal cellularity and more
      pronounced stromal overgrowth than incompletely excised lesions which did not
      recur, but these differences were not statistically significant. The recurrent
      tumours resembled the respective original lesions histologically, except in one
      case in which two local recurrences were histologically malignant. The recurrent
      tumours were controlled by further excision or mastectomy in all cases and none
      have metastasized. All four borderline tumours were completely excised at initial
      surgery and none have recurred or metastasized. One of the five malignant tumours
      recurred within two months of incomplete excision, with widespread infiltration
      of the chest wall, although the patient died of unrelated causes. The other four
      malignant tumours have not recurred. We conclude that presence of tumour at the
      margins of the excised specimen is the major determinant of local recurrence in
      phyllodes tumours and that the histological features are of secondary importance.
      These findings are discussed in relation to other published series in the
      literature.

PMID- 8522285
TI  - Pathological prognostic factors in breast cancer. IV: Should you be a typer or a
      grader? A comparative study of two histological prognostic features in operable
      breast carcinoma.
AB  - In a study of 1529 patients with primary operable breast carcinoma we have
      assessed the effect of applying both histological grade and tumour type to
      determine their comparative value as prognostic factors in human breast cancer.
      The prognostic group the patient was placed in, based on histological type alone,
      was less accurate than using grade and type together for many tumours. The
      importance of performing histological grading of ductal/no special type carcinoma
      (50% of the women in this series) is confirmed in this series. The 10-year
      survival varied from 76% for women with grade 1 carcinoma to 39% for those with
      grade 3 tumours. Some of the 'special types' of breast carcinoma including
      tubular, tubulo-lobular, invasive cribriform and grade 1 mucinous carcinomas
      behaved as would be predicted, with a greater than 80% 10-year-survival in this
      series. Others, including grade 2 mucinous carcinomas, however, behaved less well
      with a 60% to 80% 10-year-survival. Indeed, many of the histological tumour types
      including tubular mixed, ductal/no special type, mixed ductal with special type
      and lobular carcinomas of classical, solid or mixed types showed a variation in
      behaviour that could not be predicted by typing alone. Histological grade and
      tumour type, when used together, more accurately predicted prognosis. In
      multivariate analysis of a larger group of 2658 cases of primary breast
      carcinomas (including the 1529 study cases) when histological grade, lymph node
      status and tumour size were entered, grade was the most important factor in
      predicting for survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522286
TI  - Smooth muscle tumours presenting as pleural neoplasms.
AB  - Five smooth muscle tumours presenting as pleural neoplasma are presented. The
      patients were three women and two men aged between 21 and 69 years (mean = 45
      years). Clinically, one patient presented with chest pain, one with empyema and
      the other three were asymptomatic. Two of the tumours were located in the left
      side of the chest cavity and three in the right side. In four cases, the lesions
      presented as solitary pleural-based masses that varied in size from 10-18 cm in
      greatest dimension: in two of these cases, involvement of the diaphragm was
      present in addition to the pleural involvement. In one case, the tumour was seen
      to totally encase the right lung simulating the growth pattern of malignant
      mesothelioma. Histologically, three cases displayed an atypical spindle cell
      proliferation with marked cellular pleomorphism, mitoses and areas of hemorrhage
      and necrosis. The other two cases were characterized by a bland-appearing smooth
      muscle proliferation of uncertain malignant potential composed of elongated cells
      with a moderate amount of eosinophilic cytoplasm and cigar-shaped nuclei, lacking
      significant nuclear pleomorphism or mitotic activity. Immunohistochemical studies
      showed strong positivity for alpha-smooth muscle actin in all cases, and for
      desmin in four of five cases, and a focal positive reaction for keratin in one
      case. Ultrastructural examination in one of the high-grade tumours showed
      features of smooth muscle differentiation. Three of the patients were treated by
      complete surgical excision while, in the other two patients, the lesions were
      incompletely resected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522287
TI  - Frequent expression of FAS/APO-1 in Hodgkin's disease and anaplastic large cell
      lymphomas.
AB  - FAS/APO-1 (CD95) is a membrane glycoprotein belonging to the tumour necrosis
      factor/nerve growth factor receptor family, and which can trigger apoptosis in
      some lymphoid cell lines. Immunohistochemistry combined with Northern blotting
      allowed determination of the pattern of FAS/APO-1 expression in a series of Ki-1
      [CD30] positive lymphoid malignancies, including 27 Hodgkin's disease and eight
      anaplastic large cell lymphomas. CD30 negative tumours used as controls included
      27 B-cell non-Hodgkin's lymphomas. 14 T-cell non-Hodgkin's lymphomas, four
      reactive lymphadenitis, and non-lymphoid tissues. Immunohistochemistry, performed
      on frozen sections, revealed a strong FAS/APO-1 expression in 25 out of 27 (92%)
      Hodgkin's disease cases, predominantly in Reed Sternberg cells; 50 to 100% of the
      neoplastic cells in eight out of (100%) anaplastic large cell lymphoma cases were
      positive. In contrast, positive FAS/APO-1 immunostaining was observed only in 22
      out of 41 (53%) CD30 negative non-Hodgkin's lymphomas. Northern blot analysis
      detected variable amounts of the FAS/APO-1 transcript in the immunohistochemistry
      positive samples. These results suggest possible hyper-expression of FAS/APO-1
      (CD95) in Hodgkin's disease and anaplastic large cell lymphomas.

PMID- 8522288
TI  - Endovascular papillary angioendothelioma-like tumour associated with lymphoedema.
AB  - A case of endovascular papillary angioendothelioma-like tumour associated with
      lymphoedema is described. Microscopically, the tumour was composed of
      anastomosing vascular channels, some of which contained papillary projections,
      producing tuft-like or glomeruloid appearances. The dermis also showed moderate
      lymphoedema and lymphocytic infiltrate. The tumour resembled endovascular
      papillary angioendothelioma but also had several features that differed from
      typical examples: occurrence in an old patient and less prominent endothelial
      hobnail features and lymphocytic infiltrate. Three types of proliferating cells
      were observed: 1 mature flattened endothelial cells, which were strongly positive
      for endothelial markers (factor VIII-related antigen, CD31, CD34) and bound ulex
      europaeus agglutinin 1;2 immature endothelial cells with round nuclei and
      vacuolated or pale cytoplasm, which were strongly positive for CD31 and muscle
      specific actin (HHF35) and focally positive for other endothelial markers; and 3
      stromal spindle cells in papillary or glomeruloid areas, which were positive for
      vimentin, HHF35, and alpha-smooth muscle actin but negative for desmin. The
      tumour was diploid by flow cytometry. The patient was well without disease twelve
      months after the excision. We postulate that this tumour was caused by
      circulatory disturbance, namely lymphoedema associated with syringomyelia and a
      Charcot's joint.

PMID- 8522289
TI  - Immunohistochemical detection of bcl-2 protein in thymoma.
AB  - The protooncogene bcl-2 encodes a protein that inhibits apoptosis. The protein is
      expressed in most epithelial cells of the fetal thymic medulla but, to the best
      of our knowledge, no data are available on bcl-2 expression in thymoma.
      Expression of bcl-2 protein was analysed in 30 cases of thymoma by
      immunohistological staining of paraffin-embedded tissue. All cases were examined
      and classified according to the Salyer and Eggleston and the Muller-Hermelink
      classification. In four cases, the protooncogene bcl-2 was abnormally expressed
      in spindle cells of pure medullary thymoma, whereas the non-spindle cells in
      mixed and in cortical thymoma were negative. All the lymphocytes were also
      strongly positive in medullary thymoma while a few lymphocytes showed light
      staining in other thymomas.

PMID- 8522290
TI  - Granular cell tumours of the lower respiratory tract.
AB  - Granular cell tumours rarely involve the lower respiratory tract. We report eight
      cases surgically resected at our institution. There were four females and four
      males, aged between 18 to 56 years (mean 40). One tumour associated with a
      peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with
      obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1).
      These tumours were tracheal (1) or bronchial (6) and one case was located in the
      lung parenchyma. Four cases were multicentric with associated lesions located in
      a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours,
      with the largest diameter ranging from 0.5-4.5 cm, were histologically invasive.
      The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68)
      and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study
      demonstrates that, in spite of marked anatomical and clinical polymorphism, the
      rare granular cell tumours of the lower respiratory tract have a constant
      histological appearance. Our observations confirm that large tumours (> 8-10 mm)
      usually extend beyond the tracheo-bronchial cartilages and, therefore, only
      surgical treatment may avoid recurrence.

PMID- 8522291
TI  - Colorectal adenomas in surgical specimens from subjects with hereditary non
      polyposis colorectal cancer.
AB  - An understanding of the early morphogenesis of hereditary non-polyposis
      colorectal cancer is relevant to screening strategies. If most of these cancers
      were to evolve through the classical adenoma-carcinoma sequence, screening and
      removal of adenomas at relatively long intervals might be a safe and cost
      effective approach. We have reviewed 131 cancers from 117 affected members of 34
      such families. One hundred and four cancers were initial symptomatic lesions,
      eight were cancers detected in asymptomatic screened individuals, one was a
      synchronous cancer and 18 were metachronous cancers. None of the 131 cancers was
      a small, superficial type. Residual adenoma (contiguous with cancer) was present
      in three out of three (100%) in situ cancers, eight out of nine (89%) cancers
      involving only submucosa, four out of 14 (29%) cancers limited to the muscle coat
      and 13 of 105 (12%) cancers extending beyond the muscle coat. Twenty-one out of
      28 (75%) residual adenomas had a villous component. Only one was flat. Of the
      eight asymptomatic cancers, seven arose within tubular (two) or tubulovillous
      adenomas (five). The eighth was not associated with an adenoma but was 35 mm in
      diameter and extended through the bowel wall. Discrete adenomas (contiguous
      excluded) were present in 22% of surgical specimens and 31% of specimens from
      subjects older than 50 years. A relatively high proportion (30%) had a villous
      component and 43% were at least 10 mm in diameter. Patients with one or more
      discrete adenomas in their first surgical specimen were more likely to develop
      multiple cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522292
TI  - Carcinoma in situ involving sclerosing adenosis: a mimic of invasive breast
      carcinoma.
AB  - The distinction between invasive and in situ carcinoma of the breast is important
      with regard to the treatment and prognosis of the patient. When carcinoma in situ
      involves breast tissue in which the normal architecture is altered by pre
      existing sclerosing adenosis, the resulting histological picture may closely
      mimic an invasive carcinoma. We record the histopathological features in 13 cases
      where there was difficulty in identifying the presence or extent of invasive
      carcinoma. The most useful clue was attention to the low power appearances of
      distorted lobular units in the areas of malignancy and comparison with
      surrounding breast tissue which usually showed recognizable sclerosing adenosis.
      The use of immunohistochemical stains for myoepithelium (alpha-actin and S-100
      protein) and for basement membrane (collagen type IV and laminin) proved to be of
      considerable value in identifying the preservation of these features around
      glandular structures in areas of sclerosing adenosis containing in situ
      carcinoma.

PMID- 8522293
TI  - Synovial chondromatosis presenting as painless soft tissue mass--a report of 19
      cases.
AB  - Primary synovial chondromatosis is a disorder of joints, tendon sheaths and
      bursae characterized by the formation and growth of cartilaginous nodules. It
      usually presents clinically with joint symptoms and is frequently associated with
      intra-articular loose bodies. A large soft tissue mass is an unusual presentation
      which, both clinically and radiologically, raises the suspicion of malignancy.
      Nineteen cases of synovial chondromatosis presenting as soft tissue tumours were
      reviewed. They were all adjacent to joints but with no joint symptoms. Histology
      showed the typical features of benign synovial chondromatosis, including foci of
      cartilage cells showing cytological atypia. This is well recognized and does not
      indicate malignancy. Clinical follow up confirmed this with local recurrence only
      in three patients. It is important to be aware of this unusual presentation as
      the alternative diagnosis of a chondrosarcoma, as initially diagnosed in some of
      these cases, has major implications regarding the treatment of these patients.

PMID- 8522294
TI  - Lymphoepithelioma-like carcinoma of the vulvar region.
AB  - A case of lymphoepithelioma-like carcinoma of the vulvar region is described.
      Histologically, the tumour was similar to lymphoepithelioma of the nasopharynx
      but was Epstein-Barr virus negative. Infiltrating lymphocytes were predominantly
      T-cells, but also included some B-cells. Immunohistochemical stains showed
      positivity in tumour cells for cytokeratins but negativity for neuroendocrine
      markers, the melanoma-associated antigen. HMB45 and leucocyte common antigen. We
      conclude that the tumour histologically resembles lymphoepithelioma of the
      nasopharynx and lymphoepithelioma-like carcinomas of the skin, and has no
      relation to prior infection with the Epstein-Barr virus.

PMID- 8522295
TI  - Pleomorphic adenoma with extensive lipometaplasia.

PMID- 8522296
TI  - Tumoral rhinosporidiosis.

PMID- 8522297
TI  - Cutaneous epithelioid angiosarcoma exhibiting cytokeratin positivity.

PMID- 8522298
TI  - Smooth muscle tumours of the pleura.

PMID- 8522299
TI  - Hypothesis: the prenatal origins of prostate cancer.

PMID- 8522300
TI  - p53 mediated tumor cell response to chemotherapeutic DNA damage: a preliminary
      study in matched pairs of breast cancer biopsies.
AB  - Wild type p53 plays a crucial role in maintaining genomic stability in both
      normal and tumor cells in vitro. When DNA damage occurs, p53 acts as a cell cycle
      checkpoint and induces a cellular response that aims at restoring genomic
      integrity. p53 may either allow the repair of damaged DNA by inducing a transient
      G1 arrest or may eliminate the damaged cells by triggering apoptosis. Mutant p53
      fails to mediate any of these effects. From this, a p53 status-dependent response
      to therapy might be expected when tumors are treated with DNA-damaging genotoxic
      agents: Although wild type p53-harboring tumors have an intact checkpoint that
      might allow them to restore genomic integrity back to a pre-exposure level,
      mutant p53 tumors have a corrupted checkpoint that could lead to an accelerated
      loss of genomic stability. Until now, no studies have been described that examine
      such a p53-mediated effect in vivo. The authors tested this response model in
      vivo comparing 32 matched biopsy pairs from patients with breast cancer before
      and after rigorously standardized polychemotherapy. Four of the five drugs
      specifically induce a wild type p53-mediated checkpoint response. Tumor tissue
      from matched pairs of untreated and treated biopsies of the same patient were
      analyzed for treatment-associated changes of p53 protein expression by
      immunocytochemistry and, in a few available specimens, of p53 genotype changes by
      polymerase chain reaction-based DNA analysis. Treatment-associated changes of the
      p53 immunophenotype, which the authors speculate to reflect clonal selection,
      occurred in 39% (12 of 31) of the specimens. One specimen was not informative.
      Most tumors undergoing clonal selection originally harbored mutant p53 (nine of
      12), and only three of 12 tumors were wild type. This study shows that exposure
      to genotoxic agents is commonly associated with a change in p53 immunophenotype.
      Although the limited material in this cohort prevented direct analysis of genetic
      instability, these results suggest that tumors with altered p53 may be
      genomically less stable and, therefore, may be more likely to undergo treatment
      induced clonal changes than wild type tumors. This study also shows that the
      rigorous matched sample approach, although difficult to obtain, is an important
      tool that allows the in vivo assessment of the tumor response to genotoxic
      therapy in a controlled fashion.

PMID- 8522301
TI  - Distribution of lipochrome pigment in the prostate gland: biological and
      diagnostic implications.
AB  - Lipochrome pigment is characteristically found in Wolffian duct-derived
      structures including seminal vesicles and ejaculatory ducts. The presence of
      lipochrome pigment is helpful in identifying atypical histological patterns of
      seminal vesicle or ejaculatory duct that mimic prostatic adenocarcinoma. The
      authors studied the distribution of lipochrome pigment in 28 radical
      prostatectomy specimens using a modified Ziehl-Neelson stain and fluorescence
      microscopy. In all cases secretory epithelium of the central zone contained
      lipochrome pigment often in significant amounts (2 to 3+). Secretory epithelium
      from peripheral and transition zones in each of four specimens (14.3%) contained
      lipochrome pigment. In addition, occasional examples of nodular hyperplasia,
      prostatic intraepithelial neoplasia, and prostatic adenocarcinoma contained
      lipochrome pigment. The preferential distribution of lipochrome pigment in
      central zone epithelium adds further support to the hypothesis that central zone
      glands are derived embryologically from Wolffian duct (mesoderm) rather than
      urogenital sinus (endoderm), which gives rise to transition and peripheral zone
      glands. Furthermore, lipochrome pigment should not be used as the sole diagnostic
      criterion for separating atypical histological patterns of seminal vesicle and
      ejaculatory duct from those of prostatic origin.

PMID- 8522302
TI  - Immunostains for collagen type IV discriminate between C-cell hyperplasia and
      microscopic medullary carcinoma in multiple endocrine neoplasia, type 2a.
AB  - At a light microscopic level, the separation of C-cell hyperplasia and
      microscopic medullary carcinoma of the thyroid (MCT) is difficult, and it
      ultimately rests on the finding of C cells outside of the thyroid follicular
      basement membranes (FBMs). To date, this has required ultrastructural examination
      for proper documentation. The assessment of thyroidectomy specimens from patients
      with multiple endocrine neoplasia, type 2a (MEN2a), a hereditary condition in
      which there is widespread C-cell hyperplasia (CCH) and multifocal MCT, presented
      an opportunity to the authors to assess the entire range of C-cell abnormalities.
      Total thyroidectomy specimens from 17 patients with MEN2a were examined. In
      addition to hematoxylineosin (H&E) stains, representative tissue sections were
      labeled for chromogranin A and collagen type IV (CIV), using the avidin-biotin
      peroxidase complex (ABC) method. All patients in the study had multifocal C-cell
      proliferation that was both diffuse and nodular. Fifteen had microscopic MCTs,
      which were multifocal in eight instances. Three patterns of C-cell proliferation
      were recognized in CIV immunostains. The first was characterized by complete
      investment of C-cells by a continuous rim of CIV, corresponding to FBM and
      confirming an intrafollicular localization; hence, the diagnosis of CCH was made
      in such cases. The second pattern was distinctive and was typified by defects in
      the CIV layer; constituent C-cells assumed an extrafollicular location. These
      images yielded a diagnosis of micro-MCT. The latter findings were also
      accompanied by focal reduplication of basement membrane that was apparently tumor
      derived, producing a micronodular or microlobular configuration. The third
      pattern represented a combination of the first two, with C-cell nodules that were
      bounded by CIV and clearly situated in an intrafollicular location; however,
      focal reduplication of basement membranes was also evident in these cases. The
      biological significance of the third pattern of CIV staining is uncertain, but it
      may reflect the presence of a preinvasive proliferation of C-cells that is
      distinct from "usual" CCH in MEN2a.

PMID- 8522303
TI  - Human allograft vein failure: immunohistochemical arguments supporting the
      involvement of an immune-mediated mechanism.
AB  - The aim of this study was to search for signs suggestive of an ongoing immune
      mediated reaction in failed human cryopreserved venous allografts. In 15 samples,
      the authors analyzed: (1) the pattern of morphological changes; (2) the density,
      distribution, and phenotype of leukocytic infiltrate; and (3) the expression of
      class II major histocompatibility complex (MHC) antigens and inducible adhesion
      molecules. Two groups of samples could be recognized. In samples explanted before
      3 months after grafting, the structure of the vessel wall was preserved. A dense
      leukocytic infiltrate was present within the intima and around the numerous vasa
      vasorum located in medial and adventitial layers. Class II MHC antigens and
      cytokine-dependent molecules were induced on endothelial cells lining the vasa
      vasorum and on residual smooth muscle cells. In samples explanted after 3 months
      of evolution, the vessel wall has lost its normal structure and contained few
      vasa vasorum. A few leukocytes were detected around capillary vessels located in
      the peripheral connective tissue surrounding the graft. Class II MHC antigens and
      adhesion molecules were induced on endothelial cells lining the peripheral
      capillary vessels. These results suggest the involvement of an immune-mediated
      mechanism at the early stage of the evolution of failed human venous allografts.

PMID- 8522304
TI  - Angiocentric immunoproliferative lesions of the skin show lobular panniculitis
      and are mainly disorders of large granular lymphocytes.
AB  - Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin
      were studied. Histologically, three patients were grouped into AIL grade II (AIL
      II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients'
      specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in
      nine patients possessed electron-dense membrane bound granules in electron
      microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were
      positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7,
      and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and
      CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all
      patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta
      receptor in four, a pore-forming protein in four, and CD30 in three patients. The
      remaining two AIL-III patients had B-cell lymphoma. By the Southern blot
      analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta
      gene or a deletion of its germline. The preceding results in nine of 11 patients
      suggest that abnormal or neoplastic large granular lymphocytes with the
      characteristics of T and NK cells have an important role in producing the
      angiocentric/angiodestructive features and lobular panniculitis. Clinically, all
      three patients with AIL-II and four with AIL-III showed liver dysfunction,
      cytopenia, and abnormal coagulopathy during the clinical course. Five patients
      with AIL-III died within 8 months. The histological grading of AIL, patients'
      age, and limited clinical stage of the disease seem to correlate with response to
      the treatment and prognosis.

PMID- 8522305
TI  - Colorectal cancer and noncancer patients have similar labeling indices by
      microscopy and computed image analysis.
AB  - The labeling index (LI), a microscopic measurement of proliferative activity in
      colonic crypts, is proposed as an indicator of colonic cancer risk. Computed
      image analysis of proliferative regions is less labor intensive and more
      objective than is direct microscopy but has not been validated for labeling
      indices by direct comparison. The authors compared colonic crypt proliferation in
      26 cancer and 13 noncancer patients by using Ki-67 monoclonal antibody (McAb)
      labeling of flat mucosa obtained from surgically removed, frozen specimens. In
      cancer patients, the mucosa specimen was excised 10 cm away from the tumor, and
      the LI was determined microscopically for the whole crypt, the upper two thirds,
      and the upper one third of 15 crypts. Nuclear antigen levels of 15 whole crypts
      were determined by using the CAS-200 computed image analyzer (Cell Analysis
      Systems, Elmhurst, IL). Cancer and noncancer specimens were compared as were
      microscopically determined LI and stained nuclei specimens by using image
      analysis. No statistically significant difference in proliferative activity of
      whole crypts, or the upper two thirds of crypts, was observed between cancer
      specimens and noncancer specimens from using either technique. However, a
      significant correlation existed between microscopic analysis and computed image
      analysis of labeled nuclei. Computed image analysis using Ki-67 McAb labeling can
      be used instead of microscopy to determine crypt LI, but neither method can be
      used to distinguish cancer specimens from noncancer specimens.

PMID- 8522306
TI  - Immunolocalization of transforming growth factor-alpha in normal and diseased
      human gastric mucosa.
AB  - Roles for transforming growth factor-alpha (TGF alpha) in the stomach include
      cell migration and proliferation, inhibition of acid secretion, and
      cytoprotection. The authors have previously shown increased TGF alpha expression
      in rat gastric mucosa in response to acute gastric injury. They also have shown
      that TGF alpha immunoreactivity is increased in the gastric mucosa of four
      patients with Menetrier's disease. To further characterize TGF alpha
      immunoreactivity in human gastric mucosa, the authors have performed
      immunohistochemical analysis with an anti-TGF alpha monoclonal antibody on human
      gastric biopsies (n = 25) showing either normal (n = 8), mild reactive/reparative
      change in common conditions with or without associated gastritis (n = 13), and
      exaggerated mucosal change in proliferative conditions (Menetrier's disease,
      hypertrophic lymphocytic gastritis, and hyperplastic polyps) (n = 17). All normal
      biopsies showed a predictable pattern of TGF alpha immunostaining, with
      significant positivity found only in foveolar cells at the luminal surface and
      parietal cells, sparing foveolar cells in the gastric pits, mucous neck cells and
      chief cells of the gastric glands. Three patients with mild foveolar hyperplasia
      without associated inflammation did not deviate from the normal pattern except in
      foci of reactive epithelial change. Ten of 11 patients with chronic active
      gastritis, in addition to this normal staining pattern, demonstrated significant
      immunoreactivity in deeper foveolar cells and mucous neck cells showing reactive
      epithelial changes, defined as the presence of nuclear enlargement and nucleolar
      prominence with or without mucin depletion. Three cases of ulceration with
      associated reactive epithelial changes also showed increased immunoreactivity.
      Furthermore, five cases of Menetrier's disease with massive foveolar hyperplasia
      and minimal inflammation (MFH) and six cases with hypertrophic lymphocytic
      gastritis (HLG) have been studied, and both show full-thickness TGF alpha
      immunoreactivity restricted to the gastric epithelium. This pattern of staining
      is indistinguishable from that observed in two cases of hyperplastic polyps but
      differs significantly from that observed in cases of mild foveolar hyperplasia.
      These results further define patterns of TGF alpha immunostaining in normal,
      reactive/reparative and exaggerated proliferative human gastric biopsies, confirm
      participation of TGF alpha in the response to gastric mucosal injury, and provide
      additional support for a possible role for TGF alpha in the pathogenesis of
      proliferative gastric disorders including Menetrier's disease, hypertrophic
      lymphocytic gastritis, and hyperplastic gastric polyps.

PMID- 8522307
TI  - Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the
      epididymis.
AB  - Papillary cystadenoma of the epididymis is an uncommon benign lesion that may
      occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease.
      Neither immunohistochemical studies nor molecular genetic analyses of the VHL
      gene have been reported previously for this lesion. The authors describe two
      cases of clear cell papillary cystadenoma of the epididymis, both of which were
      initially confused with metastatic renal cell carcinoma. Both lesions showed
      positive immunohistochemical staining for low and intermediate molecular weight
      keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, alpha 1-antitrypsin, and alpha 1
      antichymotrypsin. Each was negative for CEA. Because clear cell papillary
      cystadenoma is similar to renal cell carcinoma histologically, and because both
      occur as components of the von Hippel-Lindau disease complex, the authors
      analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL
      gene mutation was detected in one of the two tumors by polymerase chain reaction
      followed by single-strand conformation polymorphism analysis. Direct sequencing
      revealed a cytosine to thymine transition at nucleotide 694, resulting in the
      replacement of an arginine with a stop codon after the sixth amino acid of exon
      3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene
      mutations may play a role in the initiation of tumorigenesis in sporadic
      cystadenomas of the epididymis.

PMID- 8522308
TI  - Granulomatous interstitial nephritis.
AB  - Granulomatous interstitial nephritis is a rare condition whose pathogenesis is
      poorly understood. Of 203 renal biopsies performed between 1974 to 1994 in which
      interstitial nephritis was the predominant change, granulomata occurred in 12.
      The authors reviewed the records of these patients and performed immunopathologic
      and immunohistochemical studies in their biopsies to characterize the phenotype
      of infiltrating cells. The authors used markers for T cells, B cells, and
      macrophages, and determined whether they were activated through assessment of
      upregulation of HLA-DR molecules. Additionally, the authors attempted to
      delineate whether or not tubules contributed to giant cell formation through
      assessment of intermediate filament for keratins and macrophage markers in
      epithelioid cells. Drug (aspirin, gentamycin, or combination of drugs), infection
      (Echerichia coli or various organisms), and sarcoidosis accounted for
      granulomatous inflammation in three patients each, Wegener's granulomatosis and
      oxalosis resulting from intestinal bypass in one patient each, and in one patient
      the possible cause could not be determined. Except for biopsies of granulomatous
      inflammation resulting from infection, in which neutrophils predominated, in all
      other biopsies, T cells and macrophages made up most of the inflammatory cell
      infiltrate. HLA-DR was upregulated in mononuclear cells infiltrating the
      interstitium and was expressed in proximal tubular cells and endothelial cells in
      all but biopsies of patients with sarcoidosis. In no instance was there evidence
      that tubules contributed epithelial cells to giant cell formation. These findings
      are consistent with the notion that granulomatous interstitial nephritis is a
      cell-mediated form of tissue injury in which T cell-macrophage seem to play a
      major role.

PMID- 8522309
TI  - Chordomas of the mediastinum: clinicopathologic, immunohistochemical, and
      ultrastructural study of six cases presenting as posterior mediastinal masses.
AB  - Six cases of chordomas presenting as primary posterior mediastinal tumors are
      described. Three patients were female, and three were male between the ages of 8
      and 65 years (mean, 40.6 years). In all cases, the tumors presented
      radiographically as relatively well-circumscribed, encapsulated soft tissue
      masses that did not seem to be related to the thoracic or dorsal spine. Only in
      one case, focal infiltration of bone at the level of T6-T7 was observed at the
      time of surgery. Histologically, the lesions showed a spectrum of features that
      ranged from sheets and cords of large cells with abundant vacuolated cytoplasm to
      small, stellate cells embedded within an abundant mucoid matrix. In one case, the
      cell population showed more pronounced nuclear atypia with loss of cytoplasmic
      vacuolization, frequent mitotic figures, necrosis, and solid areas characterized
      by a perivascular distribution of atypical spindle cells set against a myxoid
      stroma. Another case showed features of chondroid chordoma, with an immature
      chondroid-appearing matrix surrounding the atypical tumor cells.
      Immunohistochemical studies in all cases showed positive staining of the tumor
      cells with CAM 5.2 and broad-spectrum keratin, epithelial membrane antigen (EMA)
      and vimentin, and, to a lesser extent, with S-100 protein. Stains for muscle
      actin, carcinoembryonic antigen (CEA), and desmin were negative. Ultrastructural
      examination in two cases showed a spectrum of features that varied from large
      cells with abundant cytoplasm containing scattered ribosomes, glycogen granules,
      Golgi apparatti, abundant intermediate filaments, and small lumen formation with
      immature microvilli to smaller cells with elongated cytoplasmic processes, fewer
      intermediate filaments, rare desmosome type intercellular junctions, and
      complexes of mitochondria/rough endoplasmic reticulum. On clinical follow-up, two
      patients died with metastases to the lungs, chest wall, and liver from 1 to 3
      years after diagnosis, and two patients are alive and well without evidence of
      disease after 3 and 16 years. Chordoma should be entertained in the differential
      diagnosis of posterior mediastinal tumors. Application of immunohistochemical
      stains or electron microscopy will be of aid in separating them from other
      conditions that may histologically closely resemble these lesions.

PMID- 8522310
TI  - The differential expression of N-cadherin and E-cadherin distinguishes pleural
      mesotheliomas from lung adenocarcinomas.
AB  - Malignant mesotheliomas are highly aggressive tumors that develop most frequently
      in the pleura of patients chronically exposed to asbestos. The distinction
      between malignant mesotheliomas and tumors of epithelial origin, particularly
      peripheral lung adenocarcinoma, can be difficult despite the use of
      immunocytochemical markers and other diagnostic tools. During embryonic
      development the cadherin cell-cell adhesion molecules participate in the
      segregation of cells into different tissues. As a result of complex mechanisms of
      tissue selectivity, N-cadherin is expressed by the developing pleural mesothelial
      cells and E-cadherin is expressed by the epithelial cells of the lung. Thus, we
      postulated that N-cadherin could be used as a marker of mesothelial cells and
      mesothelial tumors, in contrast to adenocarcinomas of the lung that are tumors of
      epithelial origin. We studied the expression of N-cadherin, E-cadherin and two
      cadherin-associated proteins, alpha-catenin and beta-catenin, in 19 pleural
      mesotheliomas, 16 lung adenocarcinomas and in 2 mesothelioma cell lines using
      specific monoclonal antibodies and immunohistochemical methods. Our results show
      that all mesotheliomas express high levels of N-cadherin, regardless of their
      histological type, in contrast to lung adenocarcinomas which expressed E-cadherin
      but no N-cadherin. The cadherin-associated proteins, alpha-catenin and beta
      catenin, were present in both mesotheliomas and adenocarcinomas. Our results show
      that pleural mesotheliomas can be distinguished from lung adenocarcinomas based
      on the differential expression of N-cadherin and E-cadherin, using specific
      monoclonal antibodies and immunocytochemistry.

PMID- 8522311
TI  - EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomen.
AB  - Chromosome translocations found in neoplasms often result in the creation of
      hybrid genes encoding chimeric proteins. This case study describes a patient with
      desmoplastic small round cell tumor (DSRCT) of the abdomen, an aggressive
      neoplasm characterized by translocation of chromosomes 11 and 22. Southern
      hybridization showed that the Ewing sarcoma gene (EWS) gene was rearranged in the
      DSRCT. Reverse transcriptase-polymerase chain reaction analysis of tumor cell RNA
      revealed that exons 1 to 7 of the EWS gene were joined to exons 8 to 10 of the
      Wilms' Tumor-1 (WT-1) gene resulting in the production of a chimeric message. The
      WT-1 and EWS genes encode DNA and RNA binding proteins involved in Wilms' tumor
      and Ewing sarcoma pathogenesis, respectively. The fusion of these two genes in
      DSRCT results in the production of a putatively oncogenic protein composed of the
      zinc finger DNA binding domains of WT-1 linked to potential transcriptional
      regulatory domains of EWS. DNA sequencing revealed the genomic breakpoints of
      translocation on chromosomes 11 and 22. The genomic breakpoint on chromosome 22
      occurred in EWS intron 7 just 2 nucleotides 3' of exon 7. Polymerase chain
      reaction-based assays were developed that could detect the fused genes in the
      DSRCT tumor using either RNA or genomic DNA. The potential diagnostic use of
      these assays is discussed.

PMID- 8522312
TI  - Retrospective diagnosis of sickle cell-hemoglobin C disease and parvovirus
      infection by molecular DNA analysis of postmortem tissue.
AB  - A previously healthy 30-year-old African-American woman presented with a history
      of sickle cell trait and a nonspecific prodromal illness with severe bone pain.
      She experienced rapid clinical deterioration with seizures and cardiorespiratory
      arrest leading to death. Autopsy showed necrotic bone marrow with extensive bone
      marrow emboli. Parvovirus infection was documented by polymerase chain reaction
      (PCR) although diagnostic intranuclear inclusions or giant pronormoblasts were
      not present. The diagnosis of sickle cell-hemoglobin C disease (hemoglobin SC
      disease) was also established postmortem by DNA sequencing of PCR products. This
      case illustrates the use and versatility of PCR for analysis of formalin-fixed
      paraffin-embedded autopsy tissue.

PMID- 8522313
TI  - Focal changes of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman
      disease) associated with nodular lymphocyte predominant Hodgkin's disease.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML/Rosai-Dorfman disease)
      has, on rare occasions been identified as an isolated phenomenon in lymph nodes
      affected by malignant lymphomas. The Registry includes four cases of SHML in
      patients with non-Hodgkin's lymphomas and one with multiple myeloma. SHML has
      more recently been recorded as a focal finding in lymph nodes involved by
      Hodgkin's disease of the mixed cellularity type. We report two patients
      presenting with lymphadenopathy caused by involvement by nodular lymphocyte
      predominant Hodgkin's disease with focal changes of SHML, an association not
      previously recorded in the literature. Responsiveness of the histiocytic cells of
      SHML to B-cell derived cytokines is postulated as a mechanism for this
      phenomenon, an hypothesis previously raised in regard to the association of focal
      Langerhans cell histiocytosis with Hodgkin's disease and with non-Hodgkin's
      lymphomas.

PMID- 8522314
TI  - Ki-1 (CD30) positive anaplastic large cell lymphoma of T-cell phenotype
      developing in association with long-standing tuberculous pyothorax: report of a
      case with detection of Epstein-Barr virus genome in the tumor cells.
AB  - We report a case of CD30 positive anaplastic large cell lymphoma of T-cell
      phenotype developing in association with long-standing tuberculous pyothorax.
      Phenotypic analysis showed CD1a-, CD2+, CD3+, CD4+, CD5-, CD8-, CD10-, CD19-,
      CD20 +/-, CD21-, CD25-, CD56-, T-cell receptor (TCR) alpha/beta antigens-, and
      HLA-DR+ phenotype. Neither rearrangement of TCR beta and gamma chain genes or of
      immunoglobulin heavy chain gene was detected in DNA extract from fresh material.
      The lymphoma cells were also shown to express the latent membrane protein-1 and
      the Epstein-Barr virus (EBV)-encoded nuclear antigen-2 by immunohistochemistry
      and EBV-encoded small RNAs by in situ hybridization.

PMID- 8522315
TI  - Mucinous adenocarcinoma of the endometrium with intestinal differentiation: a
      case report.
AB  - Mucinous differentiation of endocervical type has been well documented in
      endometrial carcinoma. However, we describe an unusual case of adenocarcinoma of
      the endometrium showing diffuse histological, immunohistochemical, and
      ultrastructural evidence of intestinal differentiation. Although intestinal
      differentiation has been described in mesodermally derived tissues including
      endocervix, ovary, and urinary tract, it has not been reported in normal
      endometrium. One previous case has been reported showing this pattern in
      endometrial carcinoma. Possible histogenetic mechanisms of this pattern are
      discussed.

PMID- 8522316
TI  - Neuroendocrine cells in prostatic carcinoma.

PMID- 8522317
TI  - Counting mitoses.

PMID- 8522319
TI  - Genotype-phenotype correlation in a series of 167 deletion and non-deletion
      patients with Prader-Willi syndrome.
AB  - A total of 167 patients with Prader-Willi syndrome (PWS) was studied at the
      clinical and molecular level. Diagnosis was confirmed by the PW71 methylation
      test. Quantitative Southern blot hybridizations with a probe for the small
      nuclear ribonucleoprotein N were performed to distinguish between patients with a
      deletion (116 patient or 69.5%) and patients without a deletion (51 patients or
      30.5%). These two types of patients differed with respect to the presence of
      hypopigmentation, which was more frequent in patients with a deletion (52%) than
      in patients without (23%), and to average birth weight of females and males,
      which was lower in patients with a deletion than in patients without. Newborns
      with PWS had a lower birth weight and length at term, but normal head
      circumference in comparison with a control group. This finding aids the
      identification of the neonatal phenotype. In addition, our data confirm an
      increased maternal age in the non-deletion group.

PMID- 8522318
TI  - ACP1 and human adaptability. 1. Association with common diseases: a case-control
      study.
AB  - Human red cell acid phosphatase (ACP1) is a polymorphic enzyme closely related to
      cytosolic low molecular weight acid phosphatases, a protein family broadly
      conserved among eukaryotes. Two different functions have been proposed for ACP1:
      flavin mononucleotide (FMN) phosphatase and phosphotyrosine phosphatase (PTPase).
      Given that genetic variants of ACP1 activity are common, the enzyme could have a
      role in regulating a large spectrum of cellular functions and, in turn, disease
      susceptibility. In the present paper we report a study of ACP1 genetic
      polymorphism in 1088 normal subjects and in 1267 subjects from the population of
      Rome admitted to hospital for a number of common diseases. All ACP1 parameters
      investigated show highly significant differences among samples, suggesting that
      the enzyme may have a significant role in some of the diseases considered. In
      particular, consistent associations of ACP1 with developmental disturbances and
      with hemolytic favism have been observed. In the majority of diseases showing
      association with ACP1, only one of the two ACP1 isoforms, f and s, is involved,
      supporting the hypothesis of a functional differentiation between the two
      enzymatic fractions.

PMID- 8522320
TI  - Detection of chromosome aberrations in paraffin sections of seven gonadal yolk
      sac tumors of childhood.
AB  - Yolk sac tumors are the most frequent kind of malignant pediatric germ cell tumor
      and may have a fundamentally different pathogenesis than adult germ cell tumors.
      Since few cytogenetic studies have been performed so far, in situ hybridization
      was applied to interphase cell nuclei of seven gonadal yolk sac tumors of
      childhood in routine paraffin-embedded tissue sections. The panel of chromosome
      specific DNA probes was selected on the basis of their relevance in adult germ
      cell tumors and consisted of five DNA probes specific for the (peri)centromeric
      regions of chromosomes 1, 8, 12, 17 and/or X and/or one DNA probe specific for
      the subtelomeric region of chromosome 1 (p36.3). As in adult germ cell tumors,
      all pediatric gonadal yolk sac tumors had an increased incidence of numerical
      chromosome aberrations. All tumors showed an overrepresentation of at least three
      chromosomes. Gains of chromosome 12, which is highly specific in adult germ cell
      tumors, were diagnosed in six pediatric gonadal yolk sac tumors. The DNA indices
      determined in the paraffin-embedded tumor material correlated well with the in
      situ hybridization findings. A chromosome was either over- or underrepresented,
      compared with the corresponding DNA indices, in only a few cases. The short arm
      of chromosome 1 in adult germ cell tumors is often involved in structural
      aberrations. In pediatric germ cell tumors, the short arm of chromosome 1 is also
      a nonrandom site of structural aberrations. Moreover, the presence of a deletion
      at 1p36.3 in four out of five tumors suggests that the loss of gene(s) in this
      region is an important event in the pathogenesis of gonadal yolk sac tumors of
      childhood.

PMID- 8522321
TI  - Proliferation enhancement by spontaneous multiplication of chromosome 7 in
      rheumatic synovial cells in vitro.
AB  - Mosaic trisomy of chromosome 7 is known to occur in a variety of non-neoplastic
      hyperproliferative disorders. In long-term cell cultures established from
      rheumatic synovium with mosaic trisomy 7, we observed a continuous increase in
      the proportion of cells with trisomy 7 to over 50% by the 10th in vitro passage.
      Simultaneous in situ hybridization with a repetitive chromosome-7-specific DNA
      probe and fluorescent Ki-67 labelling showed a strong correlation between trisomy
      7 and an elevated proliferation index in cultured rheumatic synovial cells.
      Moreover, we observed a fraction of rapidly proliferating cells with up to eight
      copies of chromosome 7 as the sole cytogenetic change. Frequent somatic pairing
      of centromeres of two chromosomes 7 in interphase nuclei suggests either atypical
      non-disjunction with a persisting centromere or selective endoreduplication of
      chromosome 7.

PMID- 8522322
TI  - Sperm nuclei analysis of a Robertsonian t(14q21q) carrier, by FISH, using three
      plasmids and two YAC probes.
AB  - The meiotic segregation of chromosomes 14 and 21 was analysed in 1116 spermatozoa
      from an oligoasthenospermic carrier of a Robertsonian translocation t(14q21q),
      and in 16,392 spermatozoa from a control donor, using two-colour fluorescence in
      situ hybridisation (FISH). Two YAC probes (cloned in yeast artificial
      chromosomes) specific for regions on the long arms of these chromosomes were co
      hybridised. Of the spermatozoa, 12% were unbalanced, resulting from adjacent
      segregations. Chromosomes X, Y and 1 were also simultaneously detected in 1335
      spermatozoa from the same carrier. Whereas gonosomal disomy rates were not
      significantly different from those of the control donors, disomy 1 were slightly
      but significantly increased to 0.7%. The diploidy rate was also slightly
      increased to approximately 1% in the translocation carrier.

PMID- 8522323
TI  - Complete and precise characterization of marker chromosomes by application of
      microdissection in prenatal diagnosis.
AB  - A straightforward and extremely efficient reverse chromosome painting technique
      is described which allows the rapid and unequivocal identification of any
      cytogenetically unclassifiable chromosome rearrangement. This procedure is used
      to determine the origin of unknown marker chromosomes found at prenatal
      diagnosis. After microdissection of the marker chromosome and amplification of
      the dissected fragment by a degenerate oligonucleotide-primed polymerase chain
      reaction (DOP-PCR), fluorescence in situ hybridization (FISH) to aberrant and
      normal metaphase chromosomes with the marker-derived probe pool is performed.
      With this strategy, marker chromosomes present in amniotic fluid samples were
      successfully identified in three cases. The origin of the supernumerary markers
      was ascertained as deriving from 3p(p12-cen), 18p(pter-cen) and 9p(p12-cen),
      respectively. Since a specific FISH signal on chromosomes can be obtained within
      2 working days using a probe generated without any pretreatment from one
      chromosomal fragment only and without additional image processing devices, this
      technique is considered to be highly suitable for routine application in pre- and
      postnatal cytogenetic analysis.

PMID- 8522324
TI  - Localization of the CDKN4/p27Kip1 gene to human chromosome 12p12.3.
AB  - CDKN4/p27Kip1 is a cyclin-dependent kinase (Cdk) inhibitor implicated in G1 phase
      arrest, which negatively regulates G1 phase progression in response to TGF beta,
      and might represent a tumor suppressor gene. We report here the chromosomal
      assignment of the human CDKN4 gene to chromosome 12p12.3 in close proximity to
      highly polymorphic microsatellite markers.

PMID- 8522325
TI  - Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5.
AB  - Neurotrophic factors are essential neurone survival promoting molecules that are
      often secreted and that bind to neuronal cell surface receptors. Glial cell line
      derived neurotrophic factor, GDNF, is a potent neurotrophic factor that promotes
      the survival of dopaminergic neurones in cultures including embryonic neuronal
      cultures. We have mapped the gene encoding GDNF by two independent methods: using
      a cell hybrid panel and by fluorescent in situ hybridisation. We find GDNF lies
      on the short arm of human chromosome 5, at 5p13.1-p13.3 ability to promote
      dopamine uptake in midbrain cultures. The protein was partially sequenced and a
      rat GDNF cDNA was isolated by screening a B49 cDNA library with an
      oligonucleotide probe designed from the amino-terminus of the rat protein. Human
      GDNF sequences were isolated by screening a human genomic library with a portion
      of the rat GDNF cDNA (Lin et al. 1993). We wished to localise the GDNF gene in
      the human genome and determine its proximity to possible sites of mutation,
      particularly phenotypes affecting neuronal function.

PMID- 8522326
TI  - Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase
      (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem
      cells.
AB  - Lesch-Nyhan syndrome is caused by a severe genetic deficiency of hypoxanthine
      phosphoribosyltransferase (HPRT) and is characterized by central nervous system
      disorders, gout, and in some cases, macrocytic anemia. Women heterozygous for
      HPRT deficiency are healthy but their somatic cells are mosaic for enzyme
      deficiency owing to random inactivation of the X chromosome. Frequencies of red
      blood cells and T cells deficient in HPRT are significantly lower than the
      expected 50% in heterozygotes, suggesting that HPRT-negative blood cells are
      selected against in heterozygotes. To determine at which stage of hematopoiesis
      such selection occurs, we determined the frequencies of HPRT-negative T, B and
      erythroid precursor cells in three heterozygotes. Since the cloning efficiencies
      of T and B cells and colony forming efficiency of burst-forming unit erythroid
      (BFU-E) for sample from Lesch-Nyhan patients were similar to those of normal
      cells, HPRT deficiency does not seem to render the differentiated cells less
      efficient for proliferation. However, the frequencies of HPRT-negative T and B
      cells, and BFU-E were all less than 10% in each of the three heterozygotes.
      Although the frequencies of HPRT-negative cells showed tenfold variations between
      the heterozygotes, each heterozygote had similar frequencies of HPRT-negative
      cells in the three cell types. These results suggest that HPRT is important at
      early stages of hematopoiesis, but less so after the cells have differentiated
      into T cells, B cells and erythroid precursor cells.

PMID- 8522327
TI  - Three novel mutations in the interleukin-2 receptor gamma chain gene in four
      Japanese patients with X-linked severe combined immunodeficiency.
AB  - Three novel mutations in the IL-2R gamma chain gene were identified in four
      Japanese patients with X-linked severe combined immunodeficiency by direct
      sequence analysis of polymerase chain reaction (PCR) amplified DNA fragments.

PMID- 8522328
TI  - Chromosome 17 abnormalities and lack of TP53 mutations in paediatric central
      nervous system tumours.
AB  - Central nervous system (CNS) tumours are the most common solid tumours in
      children. Cytogenetic and molecular genetic studies of these neoplasms have
      previously shown abnormalities of chromosome 17, implicating genes on this
      autosome in tumorigenesis. To identify mutations in the TP53 tumour suppressor
      gene (17p13.1), we have sequenced the five highly conserved regions of this gene
      in 29 mixed paediatric CNS tumors. No mutations were detected by this analysis.
      In order to identify other candidate disease loci on chromosome 17, we have
      carried out a detailed deletion mapping analysis using 16 polymorphic DNA markers
      on 19 of the above tumours and an additional four cases. Abnormalities of
      chromosome 17 occurred in nine cases (39%), six of which were primitive
      neuroectodermal tumour (PNET)-medulloblastomas. These findings suggest that it is
      unlikely that the TP53 gene is directly involved in the development of common
      paediatric brain tumours. This is in contrast to findings from adult brain and
      other tumour types. Moreover, the frequency of chromosome 17 aberrations,
      especially in PNET-medulloblastomas, suggests that other genes on this chromosome
      contribute to tumourigenesis.

PMID- 8522329
TI  - Refinement by linkage analysis in two large families of the candidate region of
      the third locus (SCA3) for autosomal dominant cerebellar ataxia type I.
AB  - The autosomal dominant cerebellar ataxias (ADCA) are clinically and genetically
      heterogeneous. To date, several loci (SCAI-V) have been identified for ADCA type
      I. We have studied two large families from the northern part of The Netherlands
      with ADCA type I with a broad intra-familial variation of symptoms. In both
      families significant linkage is shown of the disease to the markers of the SCA3
      locus on chromosome 14. Through recombinations, the candidate region for SCA3
      could be refined to a 13-cM range between D14S256 and D14S81. No recombinations
      were detected with the markers D14S291 and D14S280, which suggests that the SCA3
      gene lies close to these loci. This finding will benefit the individuals at risk
      in these two families who are seeking predictive testing or prenatal diagnosis.

PMID- 8522330
TI  - Parental generalized EEG alpha activity predisposes to spike wave discharges in
      offspring.
AB  - Familial and twin studies have shown that the individual variability of the
      normal human electroencephalogram (EEG) is largely genetically determined. In
      epileptology, these genetic parameters of the EEG background activity are almost
      totally neglected. The aim of the present study has been to investigate whether a
      special genetic type of background activity might be related to the pathogenesis
      of epilepsy. EEG recordings of parents of 257 epileptic children were evaluated
      retrospectively. Some 156 healthy adults served as controls. Special attention
      was paid to alpha activity extending to the frontal region, both in bipolar and
      in referential recordings (Alpha I). Alpha I was found significantly more often
      in parents of children with primary generalized epilepsy (18%) compared with
      parents of children with focal epilepsy (8%) or controls (9%). In a second step,
      parental EEGs of children with different EEG patterns associated with epilepsy
      were studied. Alpha I was found significantly more often in parents of children
      with focal sharp waves and generalized spikes and waves (26%) than in parents of
      probands with focal sharp waves without additional generalized spikes and waves
      (8%) or in controls (9%). Parents of probands with theta rhythms and spikes and
      waves had alpha I significantly more often (18%) than parents of probands with
      theta rhythms without additional spikes and waves (8%) or controls (9%). The
      findings reveal a clear correlation between the type of EEG background activity
      in parents and the EEG characteristics in their children, thus pointing to common
      mechanisms.

PMID- 8522331
TI  - APC mutation in the alternatively spliced region of exon 9 associated with late
      onset familial adenomatous polyposis.
AB  - Germ-line mutations in the adenomatous polyposis coli (APC) gene are responsible
      for familial adenomatous polyposis (FAP). Genotype-phenotype correlation studies
      in patients with FAP have demonstrated associations of certain variants of the
      disease with mutations at specific sites within the APC gene. In a large FAP
      family, we identified a frameshift mutation located in the alternatively spliced
      region of exon 9. Phenotypic studies of affected family members showed that the
      clinical course of FAP was delayed, with gastrointestinal symptoms and death from
      colorectal carcinoma occurring on average 25 and 20 years later than usual,
      respectively. The numbers of colorectal adenomas differed markedly among affected
      individuals and the location of colorectal cancer lay frequently in the proximal
      colon. Our findings suggest that the exon 9 mutation identified in the pedigree
      is associated with late onset of FAP. The atypical phenotype may be explained by
      the site of the mutation in the APC gene. Analysis of the APC protein product
      indicated that the exon 9 mutation did not result in a detectable truncated APC
      protein. Given the location of the mutation within an alternatively spliced exon
      of APC, it is conceivable that normal APC proteins are produced from the mutant
      allele by alternative splicing.

PMID- 8522332
TI  - Germline mosaicism for an alanine to valine substitution at residue beta 140 in
      hemoglobin Puttelange, a new variant with high oxygen affinity.
AB  - Hb Puttelange [beta 140(H18)Ala-->Val] was found as a de novo mutation in two
      siblings of a French family suffering from polycythemia. Both parents were
      phenotypically normal and exclusion of paternity has been ruled out by the study
      of several polymorphic markers located on different chromosomes. The structural
      modification of Hb Puttelange was established by reversed-phase HPLC analysis of
      the tryptic digest of the abnormal chain. The amino acid composition of an
      abnormal beta T14 peptide revealed that one of the four residues of Ala was
      replaced by a Val. Tandem mass spectrometry demonstrated that the substitution
      concerned position beta 140 (H18). This hemoglobin displays an increased oxygen
      affinity that is responsible for the polycythemia. De novo mutations, as
      demonstrated again in the case of this variant, have the highest probabilities of
      detection when they lead to pathological manifestations. They may result either
      from a somatic mutation in a very early stage of the embryological development of
      the propositus or may have a parental origin with occurrence of a germline
      mosaicism. The study of the beta-globin gene indicated that this case of Hb
      Puttelange probably arose from a mutation affecting a part of the germline of the
      father, therefore leading to a true recurrence risk.

PMID- 8522333
TI  - Four adult patients with the missense mutation L206W and a mild cystic fibrosis
      phenotype.
AB  - We report molecular and clinical analyses in four unrelated patients with cystic
      fibrosis (CF) with compound heterozygosity for the L206W mutation in the cystic
      fibrosis transmembrane conductance regulator gene (CFTR). This uncommon missense
      mutation (frequency less than 1% in a sample of 336 CF chromosomes from Southern
      France) replaces a leucine by a tryptophan residue in the middle of the third
      transmembrane domain of CFTR. On the basis of the clinical features presented by
      the four patients, we postulate that the L206W might be associated with
      pancreatic sufficiency and residual transmembrane transport of chloride in lung.

PMID- 8522334
TI  - Characterization of two stop codon mutations in the galactose-1-phosphate
      uridyltransferase gene of three male galactosemic patients with severe clinical
      manifestation.
AB  - Classical galactosemia, which is caused by deficiency of galactose-1-phosphate
      uridyltransferase, is characterized by acute problems of hepatocellular
      dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation
      reverses these symptoms immediately; however, the long-term complications, such
      as mental retardation and ovarian failures are major problems in most of these
      patients. In order to investigate the molecular basis for phenotype variation in
      galactosemia, we have screened the most common mutation in the GALT gene, Q188R.
      We have further examined those patients who are heterozygous for Q188R or
      negative for this mutation by SSCP analysis and direct sequencing. In three male
      patients, we have identified, for the first time, two stop-codon mutations in the
      GALT gene, G212X (exon 7) and E340X (exon 10). Two patients of 8 and 28 years of
      age, respectively, who are compound heterozygotes for Q188R and G212X, have
      severe mental retardation and their general clinical condition is more severe
      than that of patients with missense mutations. The third patient, who is 8 years
      of age and who is homozygous for E340X, the N314D polymorphism and a silent
      substitution L218L, presents with a relatively normal physical and mental
      condition to date.

PMID- 8522335
TI  - Inheritance of migraine investigated by complex segregation analysis.
AB  - Migraine is the most common neurological disorder, affecting about 20% of adults.
      The mode of inheritance was analyzed in the two main types of migraine, migraine
      without aura (MO) and migraine with aura (MA), by complex segregation analysis
      using the computer program POINTER. We included 126 probands with MO and 127
      probands with MA from the general population. First-degree relatives and spouses
      were blindly interviewed by a neurological research fellow. The complex
      segregation analysis indicated that both MO and MA have multifactorial
      inheritance without generational difference.

PMID- 8522336
TI  - No evidence of genetic heterogeneity in Crouzon craniofacial dysostosis.
AB  - Crouzon craniofacial dysostosis (CFD) is an autosomal dominant form of
      craniosynostosis characterized by an abnormal skull shape, with hypertelorism,
      prominent eyes and midfacial retrusion. Recently, a gene for CFD has been mapped
      to chromosome 10q25-q26 and mutations in exon B of the fibroblast growth factor
      receptor 2 (FGFR2) gene have been identified. Here, we report the mapping of a
      CFD gene to chromosome 10q by close linkage to probe AFMa197wb1 at locus D10
      S1483 in six unrelated families of French ancestry (Zmax = 4.69 at theta = 0) and
      provide additional evidence of genetic homogeneity of this condition. In
      addition, we report a novel mutation in exon B of the FGFR2 gene (Cys 342 Trp) in
      familial CFD and describe recurrent mutations at codon 342 as a particularly
      frequent event in CFD. Since mutations in the extracellular domain of the FGFR2
      gene are observed in a few clinically distinct craniosynostosis syndromes (CFD,
      Jackson-Weiss, Apert and Pfeiffer), the present study gives support to the
      variable clinical expression of FGFR2 mutations in humans.

PMID- 8522337
TI  - Dinucleotide repeat polymorphism in the human ceruloplasmin gene.
AB  - We have identified a GT dinucleotide repeat polymorphism in intron 14 of the
      human ceruloplasmin gene. Observed heterozygosity for the polymorphism is 0.84.

PMID- 8522338
TI  - Polymorphic tri- and tetranucleotide repeats in exons 1 and 8 of the myelin
      oligodendrocyte glycoprotein (MOG) gene.
AB  - Polymorphic (CTC)n and (TAAA)n sequences were identified in exons 1 and 8 of the
      myelin oligodendrocyte glycoprotein (MOG) gene. The different alleles were
      detected by a method combining fluorescence labeling of polymerase chain reaction
      (PCR) products and use of an automated DNA sequencer. Although only two alleles
      differing by the number of leucine residues encoded by the (CTC)n array were
      detected at the first locus, seven alleles were identified at the second. The
      high degree of polymorphism (75%) of the tetranucleotide repeat makes this marker
      informative for association or linkage studies with diseases such as
      hemochromatosis or multiple sclerosis.

PMID- 8522339
TI  - Single nucleotide polymorphisms in the human E-cadherin gene.
AB  - We report four DNA variants in the gene coding for the cell adhesion molecule E
      cadherin. The polymorphisms affect codons 115, 133, 582 and the 3'-non-coding
      region.

PMID- 8522340
TI  - Polymorphism in the 3' untranslated region of the phenylalanine hydroxylase gene
      detected by enzyme mismatch cleavage: evolution of haplotypes.
AB  - A polymorphism was identified in 3' untranslated region of the phenylalanine
      hydroxylase gene using the newly described mutation detection method, enzyme
      mismatch cleavage. This polymorphism, 1546 G-->A, was linked to three mutations
      on several haplotype backgrounds. A group of haplotypes was identified as
      evolving from the one ancestral haplotype on which this base substitution
      occurred. The possible Celtic or Viking origin of this polymorphism is discussed.

PMID- 8522341
TI  - A human monoclonal antibody to a human self-antigen, CD2 derived from human
      peripheral blood lymphocytes engrafted in SCID mice.
AB  - To establish human hybridoma lines, production of human immunoglobulin (Ig) and
      behavior of the implanted human peripheral blood lymphocytes (PBL) were
      characterized in severe combined immunodeficiency (SCID) mice. Human PBL from
      healthy donors were injected into the peritoneal cavity of SCID mice, and they
      were immunized with self-antigen, CD2. CD45+ cells (human PBL) migrated to
      lymphoid tissues in the mice as early as 4 days, accounting for more than half
      the lymph node cells and thymocytes. The number of cells releasing human IgG
      specific to the antigen increased 3.5 weeks after immunization without the usual
      constraint that production of the IgG, an autoantibody, is prohibited by
      immunological tolerance in humans. Therefore, we established several human
      hybridomas secreting human IgG to CD2, since splenocytes and lymph node cells
      from the implanted SCID mice at 3.5 weeks were fused with a human B
      lymphoblastoid cell line. A human anti-CD2 monoclonal antibody (MAb) was
      confirmed to bind to natural CD2 on human T cells by flow cytometric analysis.
      The epitope for the MAb was identical with a portion that the ligand LFA-3
      binded, so that the MAb might reduce the inflammatory reaction caused by
      preventing activation of human T cells. Here, we report that the human immune
      system could be reconstituted in SCID mice to develop human hybridomas producing
      human MAb to a human self-antigen.

PMID- 8522342
TI  - Production of ScFv antibody fragments following immunization with a phage
      displayed fusion protein and analysis of reactivity to surface-exposed epitopes
      of the protein F of Pseudomonas aeruginosa by cytofluorometry.
AB  - To increase the possibilities of obtaining antibodies to surface-exposed epitopes
      of Pseudomonas aeruginosa protein F, we immunized mice with cloned and expressed
      oprF gene as a gIII-fusion protein displayed on the M13 phage surface. The fusion
      protein elicited mouse antibodies reacting with the purified protein F at a limit
      dilution of 1:10,000. Recombinant clones expressing antibody fragments were
      constructed from the genes of selected B cells of hyperimmunized mouse after a
      first round of panning against the protein F. Expression of single chain Fv
      (ScFv) antibody fragments to the protein of P. aeruginosa was detected by ELISA
      in 20 of 384 clones obtained after the first panning selection. The 20 positive
      clones recognizing different protein F epitopes as demonstrated by ELISA were
      assayed by flow cytometry to identify antibody fragments reacting only with
      surface-exposed epitopes of the protein F on whole bacteria; one of the 20 clones
      tested showed a level of reactivity compatible with surface-exposed epitope that
      can lead to ulterior developments in targeting studies.

PMID- 8522343
TI  - Precise epitope mapping of three monoclonal antibodies raised against tms1
      protein of fission yeast.
AB  - Recently we described the production of two monoclonal antibodies 10G2 and 10C4
      of IgG3 subclass raised against the recombinant tms1 protein of fission yeast.
      Here we introduce a new monoclonal antibody 2E2 of IgG1 subclass and present the
      precise epitope mapping of these monoclonal antibodies using tms1 deletion
      mutants and synthetically produced oligopeptides spanning the tms1 protein by
      immunoblot analysis.

PMID- 8522344
TI  - Isolation and characterization of a monoclonal anti-protein kinase CK2 beta
      subunit antibody of the IgG class for the direct detection of CK2 beta-subunit in
      tissue cultures of various mammalian species and human tumors.
AB  - A murine monoclonal anti-protein kinase CK2 beta antibody was isolated and
      characterized. The antibody detects 1 pmol of purified recombinant CK2 beta
      subunit after analysis on SDS-PAGE. Alternatively undenatured CK2 beta-subunit
      was detected by an ELISA assay either as recombinant CK2 beta-subunit or in the
      CK2 holoenzyme (alpha 2 beta 2). Here, concentrations of the first antibody of 1
      ng/ml still allowed the detection of the subunit. Immunoblotting of crude
      cellular extracts from various tissue cultures (man, mouse, and hamster), from
      human tumors, and the nonneoplastic tissue allowed the detection of the CK2 beta
      subunit. The detected epitope of this antibody was, as determined by the epitope
      analysis technique, 123GLSDI127.

PMID- 8522345
TI  - Production and characterization of monoclonal antibodies against the recombinant
      p50csk protein tyrosine kinase: a tool for signal transduction research.
AB  - p50csk is a protein tyrosine kinase (PTK) that has been reported to regulate the
      activity of other PTKs belonging to the src gene family. Several hybridoma clones
      that produce monoclonal antibodies (MAbs) directed against recombinant p50csk
      were established. Five of the clones were analyzed for their ability to recognize
      native and denatured p50csk protein after undergoing native and denaturing
      polyacrylamide gel electrophoresis followed by western blotting. In addition, the
      clones were tested for their ability to immunoprecipitate p50csk and yet maintain
      tyrosine kinase activity of antibody-bound p50csk. None of the clones cross
      reacted with pp60c-src, a PTK that shares with p50csk the homologous SH1
      catalytic domain and SH2 and SH3 regulatory domains. These MAbs can be used to
      study p50csk directly, and its role in regulating members of the src family.

PMID- 8522346
TI  - Generation and characterization of monoclonal antibodies specific for members of
      the mammalian 70-kDa heat shock protein family.
AB  - The 70-kDa heat shock proteins (hsp70) are a highly conserved, abundant, and
      ubiquitous family of proteins expressed by all organisms from bacteria to humans.
      It is well established that hsp70 family members function as molecular chaperones
      and aid in the intracellular folding of newly synthesized or denatured proteins.
      Current evidence suggests an emerging role for hsp70 family members in immune
      responses and in clinically important responses to stress and tissue damage. Here
      we report the generation and characterization of several MAbs to hsp70 family
      members. Immune responses to this highly conserved family were induced in mice by
      immunization with synthetic peptides that contain regions of the mouse
      mitochondrial hsp70 coupled to a potent helper T cell epitope derived from
      tetanus toxoid. The resulting MAbs include ones specific for the human and mouse
      mitochondrial hsp70 and others that show cross-reactivity among the family
      members and recognize the mitochondrial hsp70, the endoplasmic reticulum resident
      hsp70, Bip/grp78, the constitutively expressed cytosolic hsp70, hsc70, and the
      heat-induced member, hsp70. Significantly, these MAbs are effective in Western
      blotting, in immunoprecipitation, and in immunofluorescence, and thus should find
      applications in the purification and detection of members of this important
      family.

PMID- 8522347
TI  - The production and characterization of murine monoclonal antibodies to human
      Gadd45 raised against a recombinant protein.
AB  - The production of two different murine monoclonal antibodies to human Gadd45, a
      protein that is induced in response to DNA damage, is reported. Antibodies were
      generated in a SJL mouse using a recombinant form of the human Gadd45 protein.
      Monoclonal antibody 4TCYA1, which recognizes the denatured form of human Gadd45
      in Western blots, was selected based upon the recognition of Gadd45 induced by
      functional p53 in the human myeloid leukemia cell line, ML-1. A second monoclonal
      antibody, designated 30T.14, immunoprecipitates native human Gadd45 in lysates
      produced from RKO cells, a colorectal carcinoma cell line that expresses
      relatively high basal levels of Gadd45, as well as from cell lysates made from ML
      1 cells after exposure to ionizing irradiation (IR). Since 4TCYA1 fails to
      immunoprecipitate Gadd45, and 30T.14 fails to bind to IR-induced Gadd45 in
      immunoblotting, these two monoclonal antibodies probably recognize different
      epitopes.

PMID- 8522348
TI  - Novel monoclonal antibody reactive with thrombin-sensitive 74-kDa glycoproteins
      present on platelets and megakaryocytes both from mouse and rat.
AB  - A monoclonal antibody (designated 1C2) that reacts only with mouse platelets and
      megakaryocytes among hematopoietic cells was established by immunizing mouse
      platelets to an Armenian hamster. 1C2 reactive mouse molecule (1C2 antigen) was a
      surface glycoprotein with molecular weight of 74 kDa. Side by side comparison
      revealed that 4A5, a rat monoclonal antibody against mouse platelet,
      immunoprecipitated the identical molecule to 1C2 antigen. Of particular interest,
      1C2 also labeled rat tissues with an identical pattern to that of mouse tissues
      and recognized a 74-kDa protein from rat platelets. Reactivity of 1C2 to mouse
      and rat platelets decreased when they were treated with thrombin. Following
      thrombin treatment of mouse platelets, 1C2 reactive 69-kDa protein appeared in
      the supernatants. Mouse and rat 1C2 antigens purified on 1C2-coated beads were
      cleaved by thrombin to generate 69-kDa fragments, establishing that 1C2 antigen
      is a direct substrate for thrombin. 1C2 is the first antibody to platelets and
      megakaryocytes of mouse and rat whose reactive molecule is well characterized,
      i.e., substrate for thrombin. 1C2 can be a useful tool in studying
      megakaryocytopoiesis and thrombopoiesis in rodent systems.

PMID- 8522349
TI  - Production of a rat pancreatic polypeptide-specific monoclonal antibody and its
      influence on glucose homeostasis by in vivo immunoneutralization.
AB  - To test the effect of endogenous pancreatic polypeptide (PP) on rat hepatic
      glucose homeostasis by immunoneutralization, a rat PP-specific monoclonal
      antibody (MAb) was produced. Binding of this IgG1 monoclonal antibody was
      inhibited 50% by 350 pM rat PP. Immunohistochemistry showed that the antibody
      produced the expected pattern of endocrine cell staining in rat pancreas. Groups
      of six adult male Sprague-Dawley rats were given 5 mg of Protein-A-purified anti
      PP MAb or anti-KLH MAb (control) ip every 48 hr for 5 dosing intervals. The rate
      of hepatic glucose output during isolated liver perfusion was 0.25 +/- 0.03
      mg/g/min for the PP MAb-treated rats and 0.17 +/- 0.02 mg/g/min for the control
      group (p < 0.05). Liver glycogen content was 21.8 +/- 2.9 mg/g for the PP MAb
      treated rats and 14.7 +/- 2.4 mg/g for the control group (N = 5). Chronic in vivo
      immunoneutralization of PP with this new monoclonal antibody suggests that PP
      influences glucose homeostasis in the rat by affecting hepatic glucose output.

PMID- 8522350
TI  - A monoclonal antibody against human beta-glucuronidase for application in
      antibody-directed enzyme prodrug therapy.
AB  - The selectivity of anticancer agents may be improved by antibody-directed enzyme
      prodrug therapy (ADEPT). The immunogenicity of antibody-enzyme conjugates and the
      low tumor to normal tissue ratio calls for the use of a human enzyme and the
      development of a monoclonal antibody (MAb) against that enzyme for rapid
      clearance of the conjugate from the circulation. We isolated beta-glucuronidase
      from human liver. BALB/c mice were immunized with the roughly purified human
      liver beta-glucuronidase and we obtained an MAb designated 105. Immunoblotting
      showed reactivity with native tetrameric human beta-glucuronidase. MAb 105
      neither bound to enzyme from bovine liver, rat liver, or mouse liver nor reacted
      with other human lysosomal enzymes. The antibody appeared to be useful to further
      purify human beta-glucuronidase from human liver or human placenta to homogeneity
      by affinity chromatography. MAb 105 did not inhibit the activity of human beta
      glucuronidase. When human beta-glucuronidase was injected i.v. into BALB/c mice,
      the newly generated MAb 105 could indeed accelerate the clearance of the enzyme
      with a 50% drop in its activity within 5 min.

PMID- 8522351
TI  - Monoclonal antibodies against human collagenase and stromelysin.
AB  - Mouse monoclonal antibodies against recombinant human fibroblast procollagenase
      and prostromelysin have been generated and characterized. The epitope-containing
      domains for the antibodies have been assigned based on their immunoreactivities
      against recombinant proenzymes, mature enzymes, truncated collagenases,
      proteolytic fragments of stromelysin, and chimeric molecules constructed from
      different domains of the two enzymes. These antibodies can be divided into four
      groups: (1) antibodies that recognize the truncated 19-kDa NH2-terminal
      collagenase, (2) antibodies that recognize the C-terminal domain of collagenase
      and stromelysin, (3) antibodies that recognize a 31-kDa NH2-terminal collagenase
      fragment, and (4) antibodies that recognize the 19-kDa NH2-fragment of
      stromelysin. The prostromelysin-specific antibody 11N13 is of particular
      interest; it neutralizes stromelysin activity in a stromelysin peptide substrate
      assay, with an IC50 value of 75 nM. MAb 11N13 may be useful for in vivo and in
      vitro studies to validate the roles of stromelysin in tumor cell invasion,
      metastasis, and connective tissue disorders.

PMID- 8522352
TI  - Optimizing production of human monoclonal IgG antibodies by in vitro-primed human
      PBMC: influence of CD56+ NK cell depletion.
AB  - Freshly isolated human peripheral blood mononuclear cells (PBMC) were
      immunomagnetically depleted of CD56+ cells. When these CD56- PBMC populations
      were cultured in the presence of autologous donor serum, polyclonal activation
      with IL-2 and pokeweed mitogen (PWM) generally resulted in exclusive production
      of IgG antibodies. Fusion with SP2/O-Ag14 mouse myeloma cells was highly
      efficient and yielded a great number of IgG-producing heterohybridomas. These
      conditions were used for in vitro immunization with viable human HT29 tumor
      cells. After fusion, an increase in hybridoma clones producing IgG monoclonal
      antibodies (MAb) with HT29 specificity showing a higher portion of MAb binding to
      the surface of viable HT29 cells was recorded. This immunizing efficiency was not
      observed with HT29 membrane protein fractions or HT29 proteins integrated into
      ISCOM particles. Investigations with human anti-alpha Gal antibodies showed that
      the IgG antibodies produced by the human/mouse heterohybridomas did not contain
      the mouse-specific Gal alpha 1-3Gal epitope.

PMID- 8522353
TI  - Production of CEA-reactive monoclonal antibody (4E7) and its applications in
      immunochemistry.

PMID- 8522354
TI  - Differentiation of murine pre-B cell line by an adjuvant muramyl peptide via NF
      kappa B activation.
AB  - Muramyl dipeptide (MDP) induces NF-kappa B activation in the murine pre-B cell
      line 70Z/3, increases the expression of surface immunoglobulins, and potentiates
      the response to other inducers such as LPS or IL-1. In the present study we
      investigated whether NF-kappa B activation was related to the MDP-stimulated
      immunoglobulin expression. In a gel shift assay our results confirmed that MDP
      but not MDP(D,D), an adjuvant-inactive stereoisomer, could induce a kappa B
      binding activity in 70Z/3 cells. The LPS or IL-1 induced NF-kappa B binding
      activity was increased in the presence of MDP but not of MDP(D,D). A mutant of
      the cell line called 1.3E2, defective in NF-kappa B activations by LPS, did not
      respond to MDP. The enhanced surface immunoglobulin expression induced in the
      wild type 70Z/3 cells by MDP alone or combined to LPS, IL-1 or IFN gamma was not
      obtained in this variant. The ability of various treatments to activate the kappa
      gene enhancer was quantitatively evaluated in cells transfected with a kappa
      enhancer-luciferase expression plasmid. Treatment of transfected 70Z/3 cells with
      MDP resulted in a dose-dependent enhancement of luciferase activity, an additive
      effect to that induced by LPS or IL-1. Treatment of the defective variant
      transfected with the same construct did not result in luciferase expression after
      stimulation with the various agents. The transient transfection assays were used
      to compare the effectiveness of some MDP analogs. Two adjuvant-active compounds
      unable to enhance kappa light chain expression did not increase the basal
      response in the transfected 70Z/3 cells, indicating that NF-kappa B activation
      was not related to the adjuvant potency of MDP but correlated with the kappa
      induction.

PMID- 8522355
TI  - Production of minor lymphocyte stimulatory-1a antigens from T cell subsets.
AB  - T cell subsets that produce minor lymphocyte stimulatory (Mls) antigens were
      analyzed using mixed lymphocyte reaction (MLR) in vitro or clonal elimination
      assay in vivo. When lymph node T cells from B10.BR(Mls-1b) mice were stimulated
      with various T cell subsets from AKR (Mls-1a) mice in the presence of B10.BR
      antigen presenting cells (APC), proportions of Mls-1a reactive T cell blasts (V
      beta 6+, V beta 8.1+) increased. The stimulatory potency of CD8+ T cells was
      higher than that of CD4+ T cells. Furthermore, among either CD8+ or CD4+ T cell
      subset, CD44+ T cells appeared to produce larger amounts of Mls-1a antigens than
      CD44- T cells. More marked difference was demonstrated, when stimulator AKR T
      cells were being activated by immobilized anti-T cell antigen receptor (TCR)
      antibody during MLR. Thus, AKR T cells appeared to produce large amounts of Mls
      1a antigens on appropriate stimulations. These findings were confirmed by the
      semiquantitative analysis of mRNA levels of MTV-7 in the AKR T cell subsets. When
      CD8+CD44+ T cells from (AKR x B10.BR)F1 mice were injected intravenously into
      [B10.BR-->B10.BR] syngeneic bone marrow (BM) chimeras 1 week after BM
      reconstitution and proportions of V beta 6+ T cells were quantitated 7 weeks
      later, significant clonal elimination of V beta 6+ T cells was induced among both
      thymocyte population and lymph node T cell population in a dose-dependent manner
      of the inoculated F1 T cells. Inoculation of CD8+CD44-F1 T cells eliminated V
      beta 6+ T cells less efficiently from lymph node T cells and inoculation of
      CD4+F1 T cells induced no significant clonal elimination of the V beta 6+ T
      cells. The present findings demonstrate clearly that CD8+CD44+ T cells represent
      the cells producing large amounts of Mls-1a antigens and inducing clonal
      elimination of V beta 6+ T cells in vivo.

PMID- 8522356
TI  - Deregulated c-Fos/AP-1 accelerates cell cycle progression of B lymphocytes
      stimulated with lipopolysaccharide.
AB  - We implicated deregulated c-Fos/AP-1 in proliferative response of B lymphocytes
      stimulated with lipopolysaccharide (LPS) using splenic B cells from c-fos
      transgenic (Mx-c-fos) mice. Levels of DNA synthesis of the Mx-c-fos B cells were
      augmented in proportion to the amount of AP-1. Since the number of LPS-responding
      splenic B cells from Mx-c-fos mice was similar to that from control mice
      duplication time of the Mx-c-fos B cells (0.9 days) was much shorter than that of
      the control B cells (2.1 days), this augmentation is explained by the
      acceleration of cell cycle progression by deregulated c-Fos/AP-1. These results
      suggest that AP-1 is a major regulatory factor for cell cycle progression of B
      cells activated with LPS.

PMID- 8522357
TI  - Expression of monovalent fragments derived from a human IgM autoantibody in E.
      coli. The input of the somatically mutated CDR1/CDR2 and of the CDR3 into antigen
      binding specificity.
AB  - A hybridoma producing a polyspecific human monoclonal IgM antibody (named CB03)
      has been derived from a fusion of mouse myeloma cells with human spleen
      lymphocytes obtained from an autoimmune patient suffering from chronic idiopathic
      thrombocytopenia. The antibody was found to be encoded by somatically mutated VHI
      and VlambdaIII genes. To study the input of mutated complementarity regions
      (CDRs) into antibody specificity, the antigen binding features of the purified
      complete IgM antibody were compared with (i) a Fab fragment by hot tryptic
      digestion and (ii) recombinant monovalent fragments expressed in E. coli. In
      detail, vectors were constructed encoding for (i) rFab03 and single chain Fv03
      fragments containing the VH and VL genes connected by a linker sequence, (ii)
      scFc1.1. fragments containing the VH germline equivalent and the CB03 wild-type
      CDR3 region, and (iii) scFv fragments containing the CDR1 and CDR2 in germline
      configuration and the CDR3 expressed in the CB253 human fetal B cell hybridoma
      producing a polyspecific IgM antibody. The expression vectors contained at the 3'
      end either a (His)6 motif allowing purification on Ni(2+)-agarose or a c-myc tag
      for specifically detecting the expression products by a murine monoclonal
      antibody. Western blotting and ELISA analyses of the expression products
      indicate: (i) recombinant Fab fragments were found in the bacterial periplasm in
      extremely low amounts (1-10 micrograms from 1 litre bacterial culture), (ii) scFv
      fragments were obtained in suitable amounts from bacterial periplasm (800-1000
      micrograms/l), (iii) the monovalent recombinant fragments as well as the Fab
      obtained by tryptic digestion reflected the polyspecific antigen binding features
      of the complete IgM antibody, but did bind to the antigens with much lower
      affinity, and (iv) the CDR3 was found to be of critical importance for the
      antigen binding pattern of this particular IgM. We discuss the expression of
      recombinant scFv fragments in E. coli as a suitable method in studying the role
      of the somatic mutation in autoantibody generation.

PMID- 8522358
TI  - The induction of skin xenograft tolerance in rat-to-mouse combination could be
      affected by DFR mediating cells and antibodies against rat bone marrow cells as
      well as NK cells in the cyclophosphamide-induced tolerance system.
AB  - We investigated whether the prolongation of skin xenograft survival was obtained
      by a tolerance-inducing method using cyclophosphamide (CY), by which long-lasting
      skin allograft tolerance could be induced. The long-lasting skin allograft
      survival could be obtained in the recipient C3H/HeN (C3H) mice which were given
      100 micrograms of anti-CD4 mAb on day -3, 1 x 10(8) spleen cells (SC) plus 3 x
      10(7) bone marrow cells (BMC) derived from C57BL/6 (B6) mice on day -2,200 mg/kg
      CY on day 0, and which were grafted with allogeneic B6 skin on day 14. When the
      C3H mice were treated with anti-CD4 mAb, 1 x 10(8) s.c. plus 5 x 10(7) BMC
      derived from F344 rat and CY, the F344 skin grafts survived slightly longer
      (about 15 days) than those in untreated recipients (about 8.4 days). Such a
      prolongation of skin xenograft survival was considered donor-specific because
      rejection of 3rd party skin grafts from BN rats occurred significantly earlier
      than that of F344 skin grafts. In the recipient C3H mice treated with anti-CD4
      mAb, F344 s.c. plus BMC and CY, mixed chimerism in the periphery was detected for
      a few days after CY administration, although intrathymic chimerism was not
      detected throughout this study. In these recipient C3H mice, cytotoxic T
      lymphocytes (CTL) against F344 antigens were completely abrogated through the
      delayed footpad reaction (DFR) remained at a low but significant level. Moreover,
      though antibody (Ab) activity against F344 s.c. was completely abrogated, neither
      Ab activity against F344 BMC, which seemed to have a background common to natural
      Ab activity, nor NK activity were abrogated by this treatment. These results
      suggested that DFR mediating cells directly mediated skin xenograft rejection in
      the recipient mice treated with anti-CD4 mAb, F344 cells, and CY. Such cells may
      interfere with establishment of mixed chimerism and long-lasting skin xenograft
      tolerance, presumably in cooperation with CY-resistant Ab activity and NK cells.

PMID- 8522359
TI  - Anti-metastatic activity induced by the in vivo activation of purified protein
      derivative (PPD)-recognizing Th1 type CD4+ T cells.
AB  - The Th1 type Cd4+ T cell clone (MH2), which is capable of recognizing purified
      protein derivative from Mycobacterium tuberculosis (PPD), was examined for its
      anti-metastatic activity against melanoma. In using an in vitro proliferative
      assay, MH2 was able to recognize PPD-derived antigen in a major
      histocompatibility complex class II-restricted manner. MH2 showed neither any
      natural killer (NK) activity nor cytolytic activity against syngeneic B16
      melanoma. This clone produced interferon-gamma, tumor necrosis factor and
      interleukin-2, but not interleukin-4, when co-cultured with PPD and irradiated
      syngeneic C57BL/6 spleen cells, suggesting that this clone could thus be assigned
      to the Th1 subset. An intraperitoneal (i.p.) co-injection of 2 x 10(6) MH2 and 50
      micrograms PPD increased the NK activity of the peritoneal exudate cells (PEC)
      and the percentage of NK1.1+ cells in the PEC. These activated NK cells showed a
      low but significantly cytolytic activity against B16 melanoma. The augmented NK
      activity induced by the co-injection of MH2 and PPD was maintained by the weekly
      additional i.p. injections of PPD alone. Using a murine metastatic model, and
      i.p. co-injection of MH2 and PPD-induced anti-metastatic activity against B16
      melanoma. This anti-metastatic activity was then abrogated by the in vivo
      administration of anti-asialo GM1 serum. In addition, the NK activity in both
      peripheral blood and metastatic lungs was significantly augmented in the mice
      which were co-injected with MH2 and PPD. Taken together, these findings indicate
      that the in vivo activation of Th1 type CD4+ T cells augmented the NK activity in
      vivo and thus could potentially be an efficient immunotherapeutic weapon against
      metastasis of melanoma. These results also imply that adoptive immunotherapy
      could induce anti-metastatic activity through cytokine production but not through
      any direct cytolytic activity.

PMID- 8522360
TI  - Synthesis and surface expression of ICAM-1 in polymorphonuclear neutrophilic
      leukocytes in normal subjects and during inflammatory disease.
AB  - During bacterial peritonitis of patients on continuous ambulatory peritoneal
      dialysis (CAPD) leukocytes, particularly polymorphonuclear neutrophilic
      granulocytes (PMNs), migrate into the peritoneal cavity. However, at the site of
      inflammation PMNs are not sufficiently able to protect the host against micro
      organisms. Adhesion molecules, such as ICAM-1 (CD54), are involved in the
      interaction between endothelial cells and PMNs leading to the accumulation of
      PMNs at the site of inflammation. As PMNs are the predominant cell type in the
      peritoneal cavity in peritonitis, the aim of this study was to find out whether
      PMNs from CAPD peritonitis patients were able to express ICAM-1. Flow cytometric
      analyses with the anti-CD54 monoclonal antibody demonstrated that normal PMNs
      constitutively express slight amounts of ICAM-1. In contrast to normal PMNs,
      peritoneal PMNs from patients with CAPD peritonitis expressed high amounts of
      ICAM-1 (p = 0.003). Furthermore, ICAM-1 expression on peripheral blood PMNs of
      these patients significantly differed from PMNs from healthy donor (p = 0.01).
      Furthermore, Northern blot analysis revealed a weak signal of ICAM-1 mRNA in
      normal PMNs. However, peritoneal PMNs from CAPD peritonitis patients expressed a
      strong signal for ICAM-1 mRNA, suggesting that ICAM-1 is newly synthesized when
      PMNs invade the peritoneal cavity. In summary, this study clearly demonstrates
      that peritoneal PMNs of CAPD peritonitis express high amounts of ICAM-1 receptor
      on the level of mRNA and on the surface. Therefore, it is tempting to speculate
      that peritoneal PMNs interact amongst each other between ICAM-1 and its counter
      receptors CD11a,b/CD18 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522361
TI  - Synergy between signal transduction pathways is obligatory for expression of c
      fos in B and T cell lines: implication for c-fos control via surface
      immunoglobulin and T cell antigen receptors.
AB  - Expression of the protooncogene c-fos is controlled by three main regulatory
      pathways involving kinase C, cAMP, and calcium. Kinase C mediates its effects via
      phosphorylation of serum response factor (SRF) which interacts with the serum
      response element (SRE); cAMP and calcium mediate their effects via
      phosphorylation of CREB (cAMP regulatory element binding protein) presumably by
      activation of a protein kinase A or calmodulin-regulated kinase. We have examined
      the function of these elements in Burkitt's lymphoma cells (Ramos and Daudi) as
      well as a T lymphocytic cell line (Jurkat). We have found that stimulation of any
      one of these pathways alone has little or no effect on c-fos induction. However,
      kinase C activation (PMA stimulation) combined with either cAMP (forskolin plus
      MIX) or calcium stimulation (ionophore) leads to greatly enhanced c-fos
      induction. By contrast, cAMP in the presence of calcium shows no synergy in c-fos
      induction. Okadaic acid augments PMA- as well as calcium-mediated activation of c
      fos, and has little or no effect when combined with cAMP. The main difference
      between Ramos (B cells) and Jurkat (T cells) in the regulation of c-fos is that
      cAMP plus calcium is strongly synergistic in Jurkat and is without effect in
      Ramos. Analysis of AP-1 activity using gel mobility shift assays confirms that
      the requirements for synergy in c-fos mRNA induction are paralleled by
      requirements for synergy in induction of AP-1 activity. Signaling in B cells due
      to anti-Ig stimulation involves both kinase C activation and release of
      intracellular calcium, and results in c-fos mRNA induction. Our results indicate
      that synergy between the kinase C activation and calcium is needed for efficient
      c-fos induction since neither of these two alone induces c-fos well. That synergy
      of signaling pathways is relevant for the anti-Ig induction of c-fos is supported
      by the fact that cAMP-inducing agents and okadaic acid further enhance anti-Ig
      induction of c-fos. These results suggest that cell-specific patterns of synergy
      are an essential feature for c-fos induction and may be relevant for c-fos
      control through B and T cell antigen receptors.

PMID- 8522362
TI  - Combating cataract.

PMID- 8522363
TI  - Retinal detachment secondary to ocular perforation during retrobulbar
      anaesthesia.
AB  - The clinical characteristics and the retinal breaks associated with
      rhegmatogenous retinal detachments secondary to accidental globe perforation
      during local infiltration anaesthesia in five highly myopic eyes are presented.
      Retinal detachment was total with variable proliferative vitreoretinopathy. The
      pattern of retinal breaks was rather typical and predictable. Management involved
      vitreous surgery with internal tamponade by silicone oil in four eyes and
      perfluoropropane gas in one eye. At the last follow-up, all eyes had attached
      retina. One eye did not recover useful vision due to possible concurrent optic
      nerve damage.

PMID- 8522364
TI  - Does oxidant stress play a role in diabetic retinopathy?
AB  - The role of oxidant stress in the causation of chronic tissue damage is being
      increasingly recognized. Oxidant stress is usually countered by abundant supply
      of antioxidants. If concomitant antioxidant deficiency occurs, oxidant stress may
      produce tissue damage. We took up a study on antioxidant status in non-insulin
      dependent diabetes mellitus (NIDDM) patients with and without retinopathy and
      compared them with a control non-diabetic group. The levels of superoxide
      dismutase (SOD) were significantly reduced in all diabetic patients, i.e., those
      with and without retinopathy. However, the lowest levels were found in the
      diabetic patients with retinopathy. Vitamin E and vitamin C levels were also
      markedly lower in the diabetic patients. There was a paradoxical rise in the
      catalase and glutathione peroxidase (GPx) in the diabetic patients with
      retinopathy. This may be a compensatory mechanism by the body to prevent tissue
      damage by increasing the levels of the two alternative antioxidant enzymes.

PMID- 8522365
TI  - Ocular toxicity of tamoxifen.
AB  - Tamoxifen is an antioestrogen drug used widely in the management of oestrogen
      dependent metastatic breast carcinoma. A number of ocular complications have been
      described secondary to tamoxifen therapy. We report two patients, one of whom had
      superior ophthalmic vein thrombosis and the other who had painful proptosis and
      acute angle-closure glaucoma with choroidal detachment secondary to tamoxifen
      therapy, both of which have not been reported earlier. In both patients the signs
      and symptoms resolved rapidly after the discontinuation of tamoxifen therapy.
      Awareness of the ocular toxicity of tamoxifen is essential as prompt withdrawal
      can result in resolution of most of the complications.

PMID- 8522366
TI  - Trilateral retinoblastoma: CT evaluation.

PMID- 8522367
TI  - Primitive neuroectodermal tumour of the orbit: a case report.

PMID- 8522368
TI  - The pattern of cataract surgery in India: 1992.
AB  - Surgery for cataract blindness, a major health problem, is undergoing a rapid
      transition. This study characterizes cataract surgery in India in terms of
      practice setting and surgical procedure. A survey questionnaire was mailed in
      December 1992 to 4356 members of the All India Ophthalmological Society, resident
      in India, requesting data on cataract surgery cases within the past 12 months.
      Two thousand one hundred thirty-four (49%) ophthalmologists responded to the
      survey. Of the 1,023,070 cataract cases reported, two-thirds were private
      patients. Among private patients, 26.0% received extracapsular cataract
      extraction (ECCE) with intraocular lens (IOL) implantation and 20.7% received
      ECCE without an IOL. Among patients operated under government auspices, 9.1%
      received ECCE with IOL and 22.4% received ECCE without IOL. Overall, 82.8% of
      active surgeons reported experience with the ECCE procedure. The cataract case
      load in the private sector and the frequency of ECCE, with or without IOL
      implantation, among both private and government-operated cases is greater than
      previously recognized.

PMID- 8522369
TI  - Reverse Parinaud's syndrome due to pineal tumour.

PMID- 8522370
TI  - Spontaneous vitreous base avulsion in a patient with neurofibromatosis.

PMID- 8522371
TI  - World Bank-assisted Cataract Blindness Control Project.

PMID- 8522372
TI  - Collaboration between the National Eye Institute and Indian scientists in vision
      research.

PMID- 8522373
TI  - Effect of monocular vertical displacement of horizontal recti in A V phenomena.
AB  - Twenty-one cases of A V phenomena were subjected to monocular recession-resection
      procedure with vertical displacement of 8 mm in 11 cases and 5 mm in 10 cases.
      Both 8 mm and 5 mm shifts were found to be equally effective even in cases with
      mild or moderate cyclovertical muscle imbalance. However, in cases with oblique
      muscle dysfunction, residual vertical incomitance was observed in all such 13
      cases and should therefore be avoided. Eight cases showed horizontal incomitance
      in extreme gazes and this was more with 8 mm shift compared to 5 mm shift.

PMID- 8522374
TI  - Beta-lactam/beta-lactamase inhibitor combinations: development, antibacterial
      activity and clinical applications.

PMID- 8522375
TI  - The story of live human intestinal bacteria administered orally as a remedy.

PMID- 8522376
TI  - Thrombocytopenia--a common finding in the initial phase of tick-borne
      encephalitis.
AB  - The aim of this prospective study was to assess the frequency of thrombocytopenia
      and abnormal liver function tests in the initial phase of tick-borne
      encephalitis. In 1994, 248 adult patients presented at the Department of
      Infectious Diseases, University Medical Centre Ljubljana, with acute lymphocytic
      meningitis or meningoencephalitis and serologically confirmed tick-borne
      encephalitis virus infection. In 180/248 (72.6%) patients, typical biphasic
      course of the illness was found and 28/180 (15.6%) patients with biphasic course
      were examined in both phases of the illness. In 20 out of these 28 (71.4%)
      patients, thrombocytopenia and leukopenia were found initially, in one (3.6%)
      patient only leukopenia was recorded and three (10.7%) patients had
      thrombocytopenia without leukopenia. In four (14.3%) patients leukocyte and
      thrombocyte values were within the normal range. The lowest leukocyte number was
      1.4 x 10(9)/l and the lowest recorded thrombocyte number was 60 x 10(9)/l.
      Abnormal liver function tests were discovered in four out of 18 patients tested
      (22.2%). In conclusion, in the initial phase of tick-borne encephalitis
      thrombocytopenia and abnormal liver function tests may be found. Thrombocytopenia
      is a common finding with a frequency similar to that of well-known leukopenia,
      while abnormal liver function tests are relatively rare.

PMID- 8522377
TI  - Levels of the circulating cell adhesion molecule E-selectin and disease
      progression in HIV infection.
AB  - The levels of soluble form of E-Selectin (sEs), or endothelial-leukocyte adhesion
      molecule-1, were measured in 96 sera derived from 72 HIV-infected patients at
      different stages of the disease, 60 healthy blood donors, and 50 HIV-negative
      patients with infections, using a quantitative ELISA. Levels of sEs in HIV
      infected individuals without AIDS, according to the 1993 classification system of
      the Centers for Disease Control, were higher than normal (mean +/- SEM 48 +/- 4
      versus 35 +/- 3 ng/ml, p = 0.003). Patients with established AIDS, who were
      afebrile and had no evidence of acute concurrent infection, had even higher sEs
      serum levels (70 +/- 9 ng/ml, p = 0.009, compared to those without AIDS). A
      significant increase in clinical category disease progression was present.
      Individual concentrations of sEs correlated directly with levels of soluble
      intercellular adhesion molecule-1 (p < 0.00001) and IL-2 receptor (p = 0.001),
      but not with CD4+ T-cell counts. Zidovudine treatment was not associated with
      changes in sEs serum levels. Elevated sEs levels were also found in HIV
      seronegative patients with other bacterial and protozoal infections. Since sEs is
      a biologically active molecule, further studies should investigate the
      pathogenetic significance of circulating sEs in HIV-related disease progression,
      and assess the prognostic value of sEs determination for these patients.

PMID- 8522378
TI  - Serum antibodies to the components of diphtheria-tetanus-pertussis vaccine in
      Polish children related to vaccination status.
AB  - In Poland vaccination against diphtheria, tetanus and pertussis (DTP) is
      recommended from 2-3 months of age. Three doses at approximately 6-week intervals
      are given. A booster dose of DTP is given at 19-24 months and boosters of DT at 6
      and 14 years. In this study serum samples were obtained from 166 Polish children
      aged 2 weeks to 14 years. Vaccination status was verified from the children's
      Health Books. Antibodies were determined against pertussis toxin, filamentous
      hemagglutinin (FHA), pertactin, tetanus toxoid and diphtheria toxin. Antibodies
      of maternal original against all five antigens were detected in almost all sera
      from infants not yet vaccinated. Antibody levels increased with the number of
      vaccinations given. Children who had recently received the fourth vaccination had
      the highest antibody levels. Antibody levels decreased with time after the fourth
      vaccination for all antibodies except FHA. It was concluded that the Polish whole
      cell pertussis vaccine stimulates antibodies against pertussis toxin, FHA and
      pertactin, but that antibodies against FHA probably also are stimulated by cross
      reacting antigens. Diphtheria toxin and tetanus toxoid antibodies were above
      protective levels in all vaccinated children, but the long-term decreases justify
      the booster dose at 14 years. Twenty-five of 166 children (15%) had a vaccination
      status which deviated from recommendations demonstrating a need to increase the
      vaccination rate.

PMID- 8522379
TI  - Evaluation of two commercial amplification assays for detection of Mycobacterium
      tuberculosis complex in respiratory specimens.
AB  - To evaluate the usefulness of two standardized commercially available
      amplification assays for the detection of Mycobacterium tuberculosis: Amplicor
      test (Roche) and MTD-Amplified direct test (Gen-Probe) a total of 281 respiratory
      specimens from 198 patients with symptoms of pulmonary diseases were examined and
      compared with conventional methods. Fifty-seven specimens were positive and 218
      negative by both amplification assays. Three specimens were reactive by Amplicor
      only, and three by MTD only. In comparison with culture, the sensitivity,
      specificity, positive predictive value and negative predictive value were 96.0,
      94.8, 80.0, and 99.1%, respectively, for the Amplicor test; the corresponding
      values were 94.0, 94.4, 78.3, and 98.6%, respectively, for the MTD. However, when
      28 specimens from 14 patients on antituberculous therapy were excluded the
      improvement in PPV and specificity of both assays was obtained. In conclusion,
      both commercially available amplification tests are almost equally sensitive and
      specific and are suitable for the implementation in daily routine work in the
      specialized clinical laboratories.

PMID- 8522380
TI  - A multicentre, randomized comparative study of 500 mg versus 1,000 mg ceftazidime
      t.d.s. for treatment on gram-negative infections.
AB  - A multicentre, randomized study was performed to compare the clinical and
      bacteriological efficacy of 500 mg ceftazidime i.v. t.d.s. with 1,000 mg
      ceftazidime i.v. t.d.s. for treatment of hospitalised, non-compromised patients
      with gram-negative infections. The study was conducted in ten hospitals in The
      Netherlands. Hospitalised patients with a suspected gram-negative lower
      respiratory tract infection, complicated urinary tract infection or septicaemia
      were included. Excluded were patients with neutropenia, limited life expectancy,
      or severe renal insufficiency as well as those on antibiotics in the 48 h prior
      to entry. Ceftazidime was administered via an intravenous infusion every 8 h. For
      patients with moderately impaired renal function the frequency was reduced to 12
      h. Treatment was continued for as long as clinically indicated. Clinical response
      (cure, improvement or failure) and bacteriological response (elimination,
      persistence or non-evaluable) were assessed primarily by the investigator. Final
      assessments were made by a panel of experts without prior knowledge. In total 127
      patients were randomized, 64 patients to the 500 mg group and 63 to the 1,000 mg
      group; 47 patients were excluded from evaluation, usually due to an incorrect
      diagnosis prior to randomization. Ultimately 37 patients of the 500 mg group and
      43 patients of the 1,000 mg group were available for evaluation. Between these
      two groups of evaluable patients there were no significant differences in
      baseline characteristics, types of infection, isolated bacterial pathogens or
      treatment characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522382
TI  - Properties of Escherichia coli strains of serotype O6.
AB  - Escherichia coli isolates of serotype O6 show a broad spectrum of virulence:
      virulent strains often cause urinary tract infections; other strains are
      considered nonpathogenic. In order to analyze the properties of E. coli O6
      strains, different phenotypic and genotypic test systems were used. Our data
      indicate that O6 strains represent a rather heterogenous group of bacteria, which
      differ in the genotypic presence as well as in the phenotypic expression of
      virulence factors. In contrast to the isolates 536 (O6:K15) and RZ 475 (O6:K5)
      the strain DSm 6601, belonging to serotype O6:K5:H1, produces neither toxins nor
      mannose-resistant hemagglutinating (MRHA) adhesins. However, the strain possesses
      chromosomally located gene clusters coding for F1C (foc) and type I fimbriae
      (fim). In addition, the strain secrets the iron-uptake substances aerobactin and
      enterobactin and produces at least one microcin. The strain is serum-sensitive
      and is less virulent in in vivo animal tests.

PMID- 8522381
TI  - A randomised, multinational study with sequential therapy comparing ciprofloxacin
      twice daily and ofloxacin once daily.
AB  - In a multinational, open, randomised, controlled clinical study, 474 hospitalised
      patients with moderate or severe infections were treated with sequential regimens
      of ofloxacin or ciprofloxacin. Ofloxacin 400 mg once daily or ciprofloxacin 200
      mg twice daily were given intravenously for at least 3 days followed by oral
      treatment with ofloxacin 400 mg once daily or ciprofloxacin 500 mg twice daily.
      Overall cure rates of 86.8% (85.7%) in the ofloxacin group and 89.6 (89.5%) in
      the ciprofloxacin group were achieved in the intention-to-treat analysis (per
      protocol analysis). The overall bacteriological response rate (ofloxacin 89.5%,
      ciprofloxacin 89.0%) was comparable to the clinical cure rate. Both drugs were
      well tolerated and adverse events were rarely observed. It is concluded that
      ofloxacin and ciprofloxacin can be used successfully in the treatment of
      hospitalised patients with aerobic gram-positive and gram-negative infections.
      Ofloxacin has the advantage of a once-daily regimen, compared to the twice-daily
      regimen with ciprofloxacin.

PMID- 8522383
TI  - Serum TNF-alpha, sCD8 and sIL-2R levels in childhood tuberculosis.
AB  - In this study we have determined the serum tumor necrosis factor-alpha (TNF
      alpha), soluble CD8 (sCD8) and soluble interleukin-2 receptor (sIL-2R) levels in
      children with active pulmonary tuberculosis (n = 66) and healthy controls (n =
      20). Measurable serum TNF-alpha levels were detected in nine of 86 children
      (10.5%), all of whom belonged to the group with active disease. Serum sCD8 and
      sIL-2R determinations revealed a significant difference between the group with
      active pulmonary tuberculosis and the controls (p < 0.05). Deeper insight into
      the involvement of cytokines and T cells will provide a better understanding

PMID- 8522384
TI  - Syndrome of the anterior spinal artery as the primary manifestation of
      aspergillosis.
AB  - Aspergillosis of the central nervous system (CNS) is an uncommon infection,
      mainly occurring in immunocompromised patients. Beside cerebral involvement
      spinal cord lesions are extremely rare. To our knowledge, aspergillosis initially
      presenting with acute paraplegia due to mycotic thrombosis of the anterior spinal
      artery in a formerly healthy patient has, so far, not been reported. Neither a
      primary focus nor an underlying disease had been detected.

PMID- 8522385
TI  - Infective endocarditis of an interventricular patch caused by Acinetobacter
      haemolyticus.
AB  - A case of infective endocarditis caused by Acinetobacter haemolyticus affecting
      and interventricular patch is reported. The patient, a 21-year-old man with a
      Fallot's tetralogy who had undergone cardiovascular surgery several years before,
      received imipenem and gentamicin for 6 and 4 weeks respectively and showed a good
      response without needing surgical treatment. Endocarditis by Acinetobacter
      species is very unusual and, to our knowledge, this is the first reported case of
      infective endocarditis caused by A. haemolyticus. As the clinical characteristics
      and the response to antibiotics appear to be similar to those reported for
      infective endocarditis by Acinetobacter lwoffi, prosthetic infective endocarditis
      by A. haemolyticus is apparently not always an indication for surgical treatment.

PMID- 8522386
TI  - Breakthrough fungemia caused by Candida stellatoidea in a patient with lymphoma
      associated with shock, successfully treated with amphotericin B lipid complex.

PMID- 8522387
TI  - Re.: J. Winberg: Management of primary vesico-ureteric reflux in children-
      operation ineffective in preventing progress of renal damage (Infection 22 [1994]
      S4-S7)

PMID- 8522388
TI  - Re.: Oral administration of a certain strain of live Escherichia coli for
      intestinal disorders? (Infection 23 [1995] 51-54)

PMID- 8522389
TI  - Persistent postoperative wound infection with Pasteurella multocida: case report
      and literature review.

PMID- 8522390
TI  - Effects of balloon compliance on angiographic and clinical outcomes after PTCA.
AB  - Eighty patients underwent percutaneous transluminal coronary angioplasty (PTCA)
      for 109 lesions. Comparison was done between two groups based on balloon
      compliance. The groups were comparable in their baseline characteristics. The
      mean inflation pressure used with compliant balloons was significantly higher;
      other procedural variables were not different. The occurrence rates of intimal
      tears and coronary dissections were not significantly different. The rates of
      side branch occlusions, myocardial infarction, redo PTCA or coronary stenting and
      death were low and similar, and likewise unaffected by balloon material. We
      conclude that the occurrence of adverse outcomes after PTCA is unrelated to
      balloon material compliance.

PMID- 8522391
TI  - Left ventricle to coronary sinus fistula. An echocardiographic diagnosis.

PMID- 8522392
TI  - Cardiac pulsations in patients with isolated right ventricular infarction.

PMID- 8522393
TI  - A prescreening system for potential antiproliferative agents: implications for
      local treatment strategies of postangioplasty restenosis.
AB  - BACKGROUND: Recent advances in the understanding of the biology of restenosis
      indicate that it is predominantly caused by a multifactorial stimulation of
      smooth muscle cell proliferation. The aim of this study was to investigate the in
      vitro effect of five potential antiproliferative agents on smooth muscle cells
      from human atherosclerotic femoral arteries. METHODS AND RESULTS: Primary
      stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing
      plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted
      from femoral arteries by the Simpson atherectomy device. Cells were isolated by
      enzymatic disaggregation and identified as smooth muscle cells by positive
      reaction with smooth muscle alpha-actin. Dalteparin sodium (0.001-100 anti-Xa
      units/ml), cyclosporine A (0.005-500 micrograms/ml), colchicine (0.00004-4
      pg/ml), etoposide (0.002-200 micrograms/ml), and doxorubicin (0.0005-50
      micrograms/ml) were added to the cultures. Six days after seeding, cells were
      trypsinized and cell number was measured by a cell counter. All five agents
      tested exhibited a significant inhibition of smooth muscle cell proliferation (P
      < 0.001). After an incubation time of 48 h, the cytoskeletal components, alpha
      actin, vimentin, and microtubules were investigated. At peak concentrations, all
      five tested agents except dalteparin sodium caused severe damage to the
      cytoskeleton. CONCLUSIONS: All five potential antiproliferative agents exhibited
      a significant inhibition of smooth muscle cell proliferation. The development of
      new intravascular delivery systems may open the way for local antiproliferative
      treatment strategies in interventional cardiology.

PMID- 8522394
TI  - The aetiology of heart failure in the Chinese population of Hong Kong--a
      prospective study of 730 consecutive patients.
AB  - Heart failure is a common and serious condition in many parts of the world and is
      a frequent cause for hospital admission in the Chinese population of Hong Kong.
      There is no published information on the epidemiology of heart failure in this
      community or from mainland China. Therefore, a prospective study of consecutive
      patients admitted with the clinical diagnosis of heart failure has been carried
      out to identify the main risk factors or possible causes, and other clinical
      data. Seven-hundred thirty consecutive patients with cardiac failure were
      identified and studied. Standard clinical criteria were used for diagnosis and
      identification of the main or most likely aetiologies and echocardiography was
      done in 30%. The data analysis of the 730 patients showed the following. The
      majority were females (56%) and the prevalence of heart failure increased with
      age (mean age 73.5 +/- 11.7 years) with 76% of the women > 70 years old. In
      contrast, the men were younger with 40% < 70 years old. The main identifiable
      risk factors were hypertension (37%), ischemic heart disease (31%), valvular
      heart disease (15%), cor pulmonale (27%), idiopathic dilated cardiomyopathy (4%),
      and miscellaneous (10%). In women, hypertension was the commonest cause at all
      ages but in men aged < 70 years ischemic heart disease was equal in frequency to
      hypertension (36% and 35%, respectively). Twenty-one percent had diabetes
      compared to a community rate of 10% for this age group (odds ratio 2.25, P <
      0.0001). There was considerable overlap between diabetes, hypertension and
      ischemic heart disease. The estimated incidence rate was 3.8/1000 women and
      3.0/1000 men aged > 45 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522395
TI  - Does prevalence of migraine and Raynaud's phenomenon also increase in Korean
      patients with proven variant angina?
AB  - BACKGROUND: The incidence of coronary artery spasm in oriental patients is higher
      than that in western patients. Oriental patients with variant angina (VA)
      frequently show normal or insignificant coronary artery stenosis by angiogram,
      compared with western patients. The prevalence of migraine and Raynaud's
      phenomenon in oriental patients with VA has not yet reported. OBJECTIVE: We did a
      prospective study on the prevalence of migraine and Raynaud's phenomenon in
      patients with proven VA compared with those in two control groups using a
      radioisotope technique following ice water exposure. Simultaneously, we studied
      lipid profiles of each group. METHODS AND RESULTS: migraine was diagnosed if the
      score in part A totalled 7 or more of 26, and Raynaud's phenomenon was diagnosed
      if the score in part B totalled 4 or more of 11 by Miller et al. Technetium-99m
      labeled red blood cells (99mTc-RBC) radionuclide angiography was performed in all
      patients. Patients were included in a prospective protocol. Patients were grouped
      as follows: Group I: 20 patients with proven VA; Group II: 30 patients with
      coronary artery disease; Group III: 31 patients without heart disease. Age and
      sex of patients were not statistically different among the three groups. Migraine
      was diagnosed in 8 patients (40.0%) of group I and in 6 patients (20.0%) of group
      II and in 12 patients (38.7%) of group III. Raynaud's phenomenon was reported in
      2 (10.0%) of the patients in group I and in 5 (16.1%) of the patients of group
      III. The mean index ratio of the digital blood flow of right over left hand on
      static image was 0.85 +/- 0.07 (mean +/- S.E.M.) of the patients of group I, 0.73
      +/- 0.03 of the patients of group II and 0.74 +/- 0.04 of the patients of group
      III. The mean flow index ratio of right over left hand of the digital blood flow
      on dynamic study was 0.51 of the patients of group I, 0.43 of the patients of
      group II and 0.43 of the patients of group III. The score of migraine did not
      differ significantly among the three groups. The score of Raynaud's phenomenon of
      patients with variant angina did not differ significantly from that of patients
      in the non-coronary control group, although it differed significantly from that
      of patients in the coronary control group. But, the prevalence of migraine and
      Raynaud's phenomenon (questionnaire and radionuclide angiography) in patients of
      group I did not differ significantly from that in groups II and III. In the end,
      more patients with variant angina than coronary or non-coronary control group did
      not reach the predetermined point level for the diagnosis of migraine and
      Raynaud's phenomenon. Lipid profiles were not significantly different among three
      groups. CONCLUSIONS: This result suggests that variant angina may not be a
      manifestation of a generalized vasospastic disorder in Korean patients.

PMID- 8522396
TI  - Functional role of coronary collaterals with exercise in infarct-related
      myocardium.
AB  - We evaluated the regional myocardial blood flow in collateral dependent infarct
      related areas to examine the functional role of coronary collaterals. Regional
      myocardial blood flow was measured by positron emission tomography with 13N
      ammonia at rest and during low-grade exercise (bicycle ergometer fixed at 25 W
      for 6.5 min). The study was performed in 24 subjects, consisting of 19 patients
      with prior myocardial infarction, and five normal individuals. Regional
      myocardial blood flow was calculated using the radioactivity in myocardial tissue
      measured by positron emission tomography and the radioactivity in arterial blood.
      Concerning the infarct related area, the exercise caused myocardial blood flow to
      decrease by 18.4% (P < 0.01) in the collateral-dependent areas (n = 8) of
      angiographically positive collaterals, and to increase by 14.4% (P = not
      significant) in the areas (n = 10) of negative collaterals. Four patients in whom
      the myocardial blood flow in all walls, including the normal areas, decreased
      with exercise were excluded from this evaluation. Myocardial blood flow in
      collateral-dependent infarct-related areas appeared to decrease transiently by
      low-grade exercise. Our results suggest that collaterals increase the incidence
      of exercise-induced ischemia, but may protect the infarct related but viable
      myocardium from necrosis.

PMID- 8522397
TI  - Doppler determined aortic acceleration after dipyridamole in the prediction of
      coronary artery disease.
AB  - Change in the acceleration of aortic blood flow with stress testing is reported
      to reflect the presence of myocardial ischaemia. We studied its clinical
      usefulness when compared with dipyridamole thallium scintigraphy in 101 patients,
      of whom 64 had coronary angiography. Maximum aortic acceleration increased after
      dipyridamole (P < 0.0001), although no correlation existed between the aortic
      acceleration and evidence of thallium perfusion abnormalities. For the patients
      who had angiography, the increase in aortic acceleration was similar for those
      with no significant coronary stenoses, single vessel or multi-vessel disease.
      Compared with coronary angiography, Doppler measurement of maximum aortic
      acceleration had a sensitivity of 92% and a specificity of 37% for the detection
      of coronary artery disease. When patients with previous myocardial infarction or
      left ventricular dysfunction were excluded, there was still no relationship
      between the maximum aortic acceleration and the presence of coronary artery
      disease. We conclude that changes in the acceleration of aortic blood flow after
      dipyridamole stressing do not predict the presence or severity of coronary artery
      disease as measured from perfusion defects at thallium scintigraphy or by
      coronary angiography. We have observed a wide variability of aortic maximum
      acceleration in the evaluation of myocardial ischaemia, which we feel introduces
      serious limitations to its use in routine clinical practice.

PMID- 8522398
TI  - Effects of intracoronary infusion of an inotropic agent, E-1020 (loprinone
      hydrochloride), on cardiac function: evaluation of left ventricular contractile
      performance using the end-systolic pressure-volume relationship.
AB  - The phosphodiesterase (PDE) III inhibitor, E-1020 (loprinone hydrochloride), has
      positive inotropic and vasodilating effects. This study evaluated the positive
      inotropic effect of intracoronary E-1020 in eight patients with coronary artery
      disease and hypertensive heart disease. A direct intracoronary infusion of the
      PDE III inhibitor minimizes its vasodilating effect. After baseline hemodynamic
      measurements and coronary arteriography, a micromanometer-tipped 8F conductance
      catheter was introduced into the left ventricle to determine the hemodynamic
      effects of E-1020. Saline and vehicle were infused into the left main coronary
      artery at a rate of 2 ml/min. The dose of intracoronary E-1020 increased from 2.5
      to 5.0 and 7.5 micrograms/min. The inotropic effect of E-1020 was defined as the
      change in the slope of the end-systolic pressure-volume relationship (Emax),
      which was independent of afterload and preload. Emax significantly increased at
      infusion rates of 7.5 micrograms/min from control. Peak +dP/dt increased at an
      infusion rate of 5.0 micrograms/min or higher, while left-ventricular end
      diastolic pressure (LVEDP) decreased significantly at a rate of 5.0 and 7.5
      micrograms/min. Intracoronary infusion of E-1020 at a rate of 2.5 micrograms/min
      produced a plasma concentration of 20 ng/ml, which was identical to the minimum
      effective plasma concentration seen in previous study by intra venous infusion.
      However, at a plasma concentration of 20 ng/ml, E-1020 has more vasodilating
      effects than inotropic effects. Clinically, E-1020 appears to have a positive
      inotropic effect that depends on the extent of myocardial perfusion.

PMID- 8522399
TI  - Recurrent myocardial infarction with angina and normal coronary arteries.
AB  - Although it is well recognised that patients with ischemic heart disease can have
      normal coronary arteries on coronary angiography, most such patients have angina
      pectoris, whilst a minority have had a previous myocardial infarction. There are
      few reports of patients with recurrent myocardial infarctions and angina, but
      with normal coronary arteries on coronary angiography. We describe six patients
      who had more than one myocardial infarction, confirmed by raised cardiac enzymes
      and changes on the electrocardiogram. They subsequently developed classical
      angina and subsequent coronary angiography demonstrated no atherosclerotic
      coronary artery disease. Coronary artery spasm and diminished coronary reserve
      may have been contributory factors in these patients.

PMID- 8522400
TI  - Morpho-functional assessment of interatrial septum: a transesophageal
      echocardiographic study.
AB  - BACKGROUND: Despite the increasing number of reports on lipomatous hypertrophy of
      interatrial septum, a standardization of measurement of the dimensions of the
      interatrial septum (IAS) in the different phases of cardiac cycle has not been
      reported. Moreover, no data on modification of thickness with age and in specific
      cardiac diseases are available. OBJECTIVE: Our purpose was to study whether the
      changes of thickness and thinning of IAS may be related to age, left atrial
      dimension, cardiac cycle and different cardiac diseases. METHODS: 248 patients
      (mean age 52.7 +/- 19.9 years) underwent transthoracic (TTE) and transesophageal
      (TEE) echocardiography. IAS was measured at the constant regions anterior and
      posterior to the fossa ovalis. IAS thickness (tk), thinning (th) and % thinning
      (% th) were measured. RESULTS: IAS thickness ranged from 4 to 13 mm at the time
      of ventricular end-systolic phase (mean 6.7 +/- 1.9 mm) and from 6 to 16 mm at
      the time of atrial systole (mean 9.9 +/- 1.8 mm); significant statistical
      difference between these values was found (P < 0.01). IAS thinning ranged from 1
      to 7 mm (mean 3.42 +/- 1.8) while % IAS thinning from 18 to 76% (mean 36.53 +/-
      16.36%). Statistical analysis showed a significant positive correlation between
      age and ventricular end-systolic thickness and atrial systolic thickness and
      thinning. An insignificant correlation was found between age and % IAS thinning
      and between left atrial dimension and IAS tk and th. CONCLUSIONS: Our results
      demonstrate that IAS thickness increases by age; no correlation exists between
      IAS thinning and age. There is no difference between IAS thickness and thinning
      in patients with or without cardiac disease. We believe that the thickness of IAS
      can be considered hypertrophic only if it exceeds the value of 15 mm during both
      ventricular end-systolic and atrial systolic phases of the cardiac cycle. IAS
      thickness and thinning might be an additional parameter to evaluate systolic
      atrial function particularly with regard to maintenance of synus rhythm after
      conversion from atrial fibrillation as well as to better understand its role in
      determining the filling of ventricles in different clinical conditions.

PMID- 8522401
TI  - Hemostatic risk factors of coronary artery disease in the Chinese.
AB  - In order to find out the hemostatic risk factors of coronary artery disease in
      the Chinese, antithrombin III concentration, factor VII and fibrinogen assays,
      plasminogen activator inhibitor-1 antigen and platelet count were determined in
      51 healthy controls (mean age 63.5 years, S.D. 10.3), 55 diabetics (mean age 66.0
      years, S.D. 4.8) and 56 patients with arteriographically proved coronary artery
      disease (mean age 63.8 years, S.D. 8.7). Of the coronary artery disease group, 19
      had single vessel disease, 21 had double vessel disease and 16 had triple vessel
      disease. Sixteen of this group also had a past history of myocardial infarction.
      There was no significant difference of the hemostasis parameters between
      diabetics and controls. Fibrinogen and factor VII, but not plasminogen activator
      inhibitor, were significantly higher in coronary artery disease patients than in
      controls (P = 0.0001, both) and in diabetics (P = 0.0001, both). No significant
      difference in the parameters was found in the coronary artery disease group,
      whether the patients had single vessel disease, double vessel disease, or triple
      vessel disease, or were with or without past myocardial infarction. In the
      myocardial infarction group, fibrinogen and factor VII were significantly higher
      than in the controls (P < 0.00005 and 0.0001, respectively) and in the diabetics
      (P = 0.0002 and 0.0004, respectively). We suggest that increased levels of
      fibrinogen and factor VII, but not plasminogen activator inhibitor, would be the
      hemostatic risk factors of coronary artery disease in the Chinese.

PMID- 8522402
TI  - Advantages of immediate two-dimensional echocardiography in patients with acute
      cardiac ischemic events.
AB  - We hypothesized that the assessment of kinetic alterations on two dimensional
      echocardiogram (2DE) would provide greater diagnostic information than clinical
      symptoms and ECG changes only. The study was aimed to determine sensitivity of
      2DE in patients with cardiac ischemic events and to improve the indications to
      thrombolysis. Three-hundred ninety-one patients (87 F; 304 M) hospitalized for
      suspected acute myocardial infarction (AMI), first episode, within 4 h from the
      onset of symptoms, suitable for thrombolysis Killip class I-II and with unstable
      angina (UA), were admitted in the study. Patients had to show ECG changes and
      alterations of segmentary motion on 2DE performed at entry, or 2DE alterations
      without ECG changes. The 2DE variables analyzed included right ventricular
      function and left ventricular systolic function. Thrombolysis was performed when
      2DE and ECG changes were evidenced at the same time and when 2DE alterations
      without ECG changes were observed. Patients with UA treated with heparin alone
      were also studied. The presence of segmentary motion alterations was mandatory.
      RESULTS: Inferior AMIs, 87 patients (60 +/- 13 years), anterior AMI, 169 patients
      (61 +/- 11 years); UA group subjected to thrombolysis, 87 patients (62 +/- 12
      years); UA group treated with heparin, 48 patients (62 +/- 12 years). We noted
      only one patient false negative, and five patients false positive. Alterations of
      right ventricular function were observed in 24, 14 and nine patients with
      inferior, anterior AMI and UA, respectively. Normal ECG at entry was observed in
      seven, two and seven patients with inferior, anterior AMI and UA,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522403
TI  - Recurrent syncope of unknown origin: value of permanent pacemaker insertion.
AB  - We studied the outcome of permanent pacing in those with a history suggestive of
      Stokes-Adams attacks but no electocardiographic evidence of bradyarrhythmia. Of
      11 patients who fulfilled pre-defined inclusion criteria, over a mean follow-up
      period of 5.4 years, seven patients were free of symptoms and two were much
      improved following pacing. We suggest that in those with a clinical history of
      frequently recurrent Stokes-Adams attacks and a normal electrocardiogram,
      pacemaker insertion may be a reasonable course of action.

PMID- 8522404
TI  - Isolated right ventricular infarction in a case of hypertrophic cardiomyopathy.
AB  - A case of isolated right ventricular infarction in a young female with
      hypertrophic cardiomyopathy is reported. This case highlights the importance of
      detailed evaluation of right ventricle in cases with hypertrophic cardiomyopathy.

PMID- 8522405
TI  - Coronary ventricular fistula as a complication of PTCA: a case report and
      literature review.
AB  - A 58-year-old man with previous myocardial infarction and coronary bypass surgery
      underwent angioplasty to a totally occluded venous graft to the left anterior
      descending artery (LAD). The procedure resulted in a coronary-ventricular
      fistula. Prolonged inflation of the balloon in the proximal part of the graft
      resulted in obliteration of the fistula with little haemodynamic compromise.

PMID- 8522406
TI  - Cardiac valve involvement in systemic lupus erythematosus and primary
      antiphospholipid syndrome: lack of correlation with antiphospholipid antibodies.
AB  - The aim of this study was to determine the prevalence of cardiac valve disease in
      systemic lupus erythematosus or in patients with primary antiphospholipid
      syndrome and to assess the role of the antiphospholipid antibodies as risk factor
      for endocardial lesions. We studied 39 consecutive patients with systemic lupus
      erythematosus (mean age 34 +/- 12 years, 38 female and one male), 20 women with
      primary antiphospholipid syndrome (mean age 32 +/- 4 years) and 20 normal
      subjects (mean age 35 +/- 8 years, 15 female and five male). All patients with
      primary antiphospholipid syndrome had increased levels of serum anticardiolipin
      antibodies and recurrent fetal abortions; some of them also had arterial and/or
      venous thrombosis and/or thrombocytopenia. M-mode, two-dimensional and Doppler
      echocardiography were performed in all patients. IgG anticardiolipin antibodies
      were measured by an enzyme-linked immunosorbent assay. Valvular lesions were
      observed in 15 patients (38%) with systemic lupus erythematosus. These
      abnormalities included: mitral valve thickening or vegetation, mitral valve
      prolapse and aortic valve vegetation; mitral, aortic and tricuspid regurgitation;
      mitral stenosis. None of the patients with primary antiphospholipid syndrome and
      of the normal subjects was found to have valvular abnormalities. In systemic
      lupus erythematosus, high levels of anticardiolipin antibodies were detected in
      73% of the patients with valvular lesions and in 67% of the patients without
      valvular lesions (P > 0.05). We conclude that valvular involvement is frequent in
      patients with systemic lupus erythematosus but it is apparently unrelated to
      antiphospholipid autoimmunization.

PMID- 8522407
TI  - Circulating alpha-actin in non-insulin-dependent diabetics with autonomic
      dysfunction.
AB  - Silent myocardial ischemia in non-insulin-dependent diabetic patients occurs
      frequently in association with autonomic dysfunction, suggesting that diabetic
      neuropathy may be involved in the development of this disorder. Repeated episodes
      of silent myocardial ischemia can induce myocardial necrosis. Recently, actin was
      detected with Western blotting in the serum of patients with acute myocardial
      infarction and angina pectoris. We found that a large proportion of non-insulin
      dependent diabetic patients with neuropathy also have detectable circulating
      concentrations of alpha-actin, and therefore suggest that the determination by
      immunoblotting of serum alpha-actin in such patients is an effective method to
      detect myocardial cell suffering and to identify patients that may need special
      consideration.

PMID- 8522408
TI  - Captopril does not affect plasma endothelin-1 during thrombolysis and
      reperfusion.
AB  - Studies showed that endothelin-1 (ET-1) was increased in the acute myocardial
      infarction (AMI). Experimental studies reported that captopril was able to reduce
      ET-1 secretion, and that ET-1 was increased during reperfusion. This study was
      aimed to verify if captopril was able to reduce plasma ET-1 during thrombolysis
      in AMI. Seventy-three patients, hospitalized for suspected AMI within 4 h from
      the onset of symptoms suitable for thrombolysis (1st episode), Killip class 1-2,
      were randomized (double blind) into two groups: group 1 (37 pts), 8 F/29 M,
      received captopril, 6.25 mg, orally 15 min before thrombolysis. Group 2: (36 pts)
      8 F/28 M, received placebo before thrombolysis. All patients met the reperfusion
      criteria. Plasma ET-1 were checked on admission, at 1 h and at 2 h, after
      starting thrombolysis. Group 1 contained ten unstable angina, 17 anterior and ten
      inferior AMIs. Group 2 contained ten unstable angina, 16 anterior and ten
      inferior AMIs. Mean concentrations of ET-1: Unstable angina: group 1, basal-
      4.56, at 1 h--4.47, 2 h--5.89 pg/ml; group 2: basal--4.17, at 1 h--4.59, 2 h-
      5.24 pg/ml. Inferior AMI: group 1: basal--6.87, 1 h--7.75, 2 h--8.47; group 2:
      basal--6.34, 1 h--6.68, 2 h--7.98 pg/ml. Anterior AMI: group 1: basal--7.17, 1 h-
      7.93, 2 h--10.76 pg/ml (between basal and 2-h samples P < 0.05); group 2: basal-
      7.46, 1 h--7.51, 2 h--10.74 pg/ml. Differences between the two groups were not
      significant. Our data suggest that captopril does not affect plasma ET-1 during
      thrombolysis.

PMID- 8522409
TI  - Left ventricular volume in thrombolysed patients with acute anterior myocardial
      infarction: the effect of captopril and xamoterol.
AB  - We measured left ventricular volume in 70 asymptomatic patients after first Q
      wave anterior myocardial infarction in order to determine whether ventricular
      dilatation occurs and whether there is evidence for its attenuation or prevention
      by treatment with captopril or xamoterol--PRevention Of VEntricular Dilatation?:
      the PROVED? study. 77% of patients received thrombolytic treatment. Patients were
      randomised a mean of 11 days after infarction to receive either captopril 25 mg
      three times daily, xamoterol 200 mg twice daily or matching placebo. After 6
      months of treatment, 6 patients from the placebo group (n = 24), 1 from the
      captopril group (n = 23) and 3 from the xamoterol group (n = 23) had been
      withdrawn from the study because of clinical complications. Left ventricular
      volume was measured using magnetic resonance imaging, before randomisation and
      after 6 months of treatment. Changes in left ventricular end-diastolic and end
      systolic volume after 6 months of treatment were defined prospectively as the
      primary endpoints. Mean initial end-diastolic volume index was 85 (S.D. 19)
      ml/m2, mean end-systolic volume index was 45 (S.D. 18) ml/m2, and mean ejection
      fraction was 48 (S.D. 11)% for the whole group. There was no significant change
      in left ventricular volume index in the placebo or either treatment group after 6
      months of treatment. Only minimal left ventricular dilatation was evident at 11
      days. No further increase in left ventricular volume occurred after six months
      and there was no additional benefit from treatment with either captopril or
      xamoterol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522410
TI  - Clinical and invasive 7-month follow-up of a patient with a synthetic coronary
      graft.
AB  - The PossisR polytetrafluoroethylene Permaflow is a synthetic coronary graft which
      incorporates a Venturi resistor and which is anastomosed to the superior vena
      cava. Multiple anastomoses to the coronary vessels can be established in sequence
      until the graft is finally connected to the aorta. This aortocaval fistula
      enables permanent flow within the synthetic graft. We present the post-operative
      clinical and invasive findings of a 69-year-old female patient with a PossisR
      coronary graft. Follow-up angiography 3 and 7 months post-operatively showed
      patency of both coronary anastomoses and sufficient run-off to the native vessel
      segments. The left-right shunt induced by the graft was hemodynamically
      insignificant. Left ventricular function had improved significantly. 30 MHz
      intravascular ultrasound of the proximal part of the PossisR graft did not show
      an extra inner layer at the luminal side of the synthetic graft wall, so that
      relevant intimal thickening could be excluded after an interval of 7 months post
      implantation. Using an intravascular imaging technique, focal atherosclerotic
      lesions or thrombotic graft wall alterations could also be ruled out.

PMID- 8522411
TI  - Long-term prognosis after thrombolytic therapy for acute myocardial infarction.
AB  - In order to clarify the relationship between the patency of the infarcted
      arteries and subsequent long-term prognosis after thrombolytic therapy, we
      evaluated 116 patients with acute myocardial infarction treated with
      intracoronary (112 patients) or intravenous (four patients) urokinase. Patients
      treated with angioplasty after thrombolysis were excluded. The infarcted vessel
      was recanalized in 52 patients (patent group) and was not in the remaining 64
      patients (occluded group). Five-year and 8-year follow up was conducted in 91%
      and 81% of the patients, respectively. The 1-, 5- and 8-year survival rate for
      the patent and occluded group was 91.8 and 80.9%, 80.8 and 79.2%, and 75.9 and
      75.6%, respectively. The survival rate in the patent group tended to be higher
      than that in the occluded group up to 4 years. However, after 5 years, both
      groups showed similar survival rates. Therefore, reopening of the infarcted
      arteries with thrombolysis was not an independent predictor for late cardiac
      death (Cox regression analysis).

PMID- 8522412
TI  - Significance of detection of enterovirus RNA in myocardial tissues by reverse
      transcription-polymerase chain reaction.
AB  - Enteroviruses are known to have association with human myocarditis and dilated
      cardiomyopathy (DCM). We screened biopsy specimens from patients with active
      myocarditis or DCM, and myocardial tissues from autopsy cases without cardiac
      diseases using polymerase chain reaction (PCR) gene amplification. Positive
      enteroviral signals were demonstrated from 4 of 5 patients with active
      myocarditis (80%), 7 of 42 patients with DCM(17%) and 3 of 27 autopsies (11%).
      Out of 7 PCR positive patients with DCM, 3 cases showed hypertrophy and disarray
      of cardiocytes, fibrosis in the interstitium, and a few inflammatory infiltrates.
      The remaining 4 cases with DCM and 3 PCR positive autopsy cases did riot exhibit
      histological findings compatible with those in myocarditis. Our results support
      the observations that enteroviruses are common aetiologic agents of myocarditis,
      and some cases of DCM. Our results also suggest the possibility that in some
      cases enteroviruses may persist in the myocardium without causing apparent
      pathological changes.

PMID- 8522413
TI  - Ischemic episodes in 24-h ambulatory electrocardiograms of elderly persons: the
      Cardiovascular Health Study.
AB  - We examined correlates of ischemic episodes in 24-h ambulatory electrocardiograms
      (ECG) in a sample of 1511 men and women 65 years old and older. Ischemic episodes
      had a high prevalence period during early afternoon and also during morning hours
      after awakening, and the overall prevalence was 13% in men and 9% in women (P <
      0.001 for gender difference). The prevalence was 9.6% in participants with no
      history of myocardial infarction and no major or minor resting ECG abnormalities.
      In multivariate analysis by logistic regression, being on digitalis medication
      was associated with over a three-fold risk of ischemic episodes, with an odds
      ratio (95% confidence limits) of 3.21 (1.80 to 5.74). Left ventricular
      hypertrophy by ECG and atrial fibrillation had almost a three-fold excess risk of
      ischemic episodes, with odds ratios 2.81 (1.37 to 5.74) and 2.63 (1.17 to 5.91),
      respectively. Isolated ST-T abnormalities had almost a two-fold excess of
      ischemic episodes, with an odds ratio of 1.89 (1.01 to 3.54). Being overweight
      was associated with a 33% reduced likelihood of ischemic episodes after
      adjustment for other factors, with an odds ratio of 0.67 (0.46 to 0.98). It is
      concluded that the prevalence of silent ischemic episodes is high in older men
      and women.

PMID- 8522414
TI  - The risks of thrombolysis in patients without acute myocardial infarction.
AB  - The risk of administering thrombolysis to patients with suspected myocardial
      infarction who subsequently do not sustain an infarct, but develop complications
      associated with thrombolysis is of concern to all physicians. The objective of
      this study was to ascertain the effect of altering the criteria for the
      administration of thrombolysis on the number of patients who received
      thrombolysis in the absence of infarction. During 1990 and 1992 details of all
      admissions with chest pain were recorded. During 1991 the policy for the
      administration of thrombolysis was altered so that only patients with ST
      elevation were eligible. A total of 1473 patients were admitted with chest pain
      in 1990 and 1967 in 1992. Of the patients admitted in 1990, 663 (45%) had
      confirmed infarction of whom 378 (57.0%) received thrombolysis. In 1992, 855
      (43%) were admitted with infarction and of these 450 (52.6%) had thrombolytic
      therapy. 118 patients had no evidence of myocardial infarction, but received
      thrombolysis. 91 (77.1%) were admitted in 1990 and 27 (22.9%) in 1992 (P < 0.01).
      Of these only 24 (20%) subjects had ST elevation or bundle branch block on the
      admission electrocardiograph and 41 (35%) had normal tracings. Four (3%) subjects
      had serious complications of whom one (0.8%) died. The implementation of ECG
      criteria resulted in a significant reduction in the number of patients without
      infarction who received thrombolysis, but did not significantly alter the rate of
      thrombolysis in those with definite myocardial infarction.

PMID- 8522415
TI  - Diet, central obesity and prevalence of hypertension in the urban population of
      south India.
AB  - Central obesity is a strong predictor of higher prevalence of diabetes,
      hypertension and coronary artery disease among Indian immigrants to Britain. To
      test this hypothesis in Indians, 1569 adults, between 25 and 64 years of age,
      from 750 randomly selected households (representative of 0.52 million population
      of Trivandrum city, Kerala) were selected for this study. The response rate was
      roughly 95% and the sample consisted of 1497 individuals (737 males and 760
      females). The survey methods included dietary diaries for 7-day food intake
      record, blood pressure measurements using a mercury sphygmo-manometer and
      anthropometric measurements. The prevalence rates of hypertension between 25 and
      64 years was 189/1000 (95% confidence limits 85-360) and between 45 and 64 years
      was 335/1000 (95% confidence limits 210-460) which is higher than in Western
      populations. The prevalence was higher in males than females in the younger age
      groups and comparable in both sexes in the upper age groups. The prevalence of
      central obesity was significantly higher among male (77.2 vs. 48.9%) and female
      (84.0 vs. 51.4%) hypertensives compared to non-hypertensive subjects; however,
      mean body weight, body mass index and waist-hip ratio (WHR) were lower among
      Indian men compared to a British comparison group. Thus, comparison of Indian men
      with Britons showed that obesity, salt and alcohol intake, sedentariness, smoking
      and dietary fat intake do not explain the cause of higher prevalence of
      hypertension among South Indian men from Kerala.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522416
TI  - Physicians' approach to the management of hypertension in a developing community.
AB  - General physicians' (GP) approach to the management of hypertension was assessed
      by a standard questionnaire. Each of the 42 physicians studied see about 42
      patients in a clinic day. Over half do not usually measure the blood pressure
      (BP) of all new patients. A third do not investigate before starting therapy.
      Over half commence drug therapy with less than three BP readings, while over two
      thirds do so from appropriate BP levels. Over 70% employ sedatives in treatment
      (50% as the only initial therapy); 45% employ parenteral drugs from a diastolic
      BP of 110 mmHg. Over 40% do not educate their patients on the implications of
      hypertension and the need for regular treatment and follow-up, but most give
      follow-up appointments. Patients are requested to stop therapy once BP is
      normalised by 25.9% of GPs. These practices were not significantly influenced by
      years of experience or by being a GP in a teaching hospital system (P > 0.1 and P
      > 0.5, respectively). The study suggests that physician recognition and
      management of hypertension is still inadequate and this might in part be related
      to a general heavy patient load. In addition, continued medical education is
      essential for physicians for the purpose of improving our management skills.

PMID- 8522417
TI  - Torsade de pointes and T-wave alternans in a patient with brainstem hemorrhage.
AB  - Torsade de pointes, a form of life-threatening ventricular arrhythmia associated
      with QT prolongation, is rarely reported in intracranial hemorrhage. T-wave
      alternans is recently considered a risk marker for ventricular arrhythmias. To
      our knowledge, we report the first case of brainstem hemorrhage in which the
      patient presented with torsade de pointes and T-wave alternans. The implication
      of this association is discussed.

PMID- 8522418
TI  - Left main coronary artery spasm.

PMID- 8522419
TI  - Programmed cell death in development.
AB  - Although cell death has long been recognized to be a significant element in the
      process of embryonic morphogenesis, its relationships to differentiation and its
      mechanisms are only now becoming apparent. This new appreciation has come about
      not only through advances in the understanding of cell death in parallel
      immunological and pathological situations, but also through progress in
      developmental genetics which has revealed the roles played by death in the cell
      lineages of invertebrate embryos. In this review, we discuss programmed cell
      death as it is understood in developmental situations, and its relationship to
      apoptosis. We describe the morphological and biochemical features of apoptosis,
      and some methods for its detection in tissues. The occurrence of programmed cell
      death during invertebrate development is reviewed, as well as selected examples
      in vertebrate development. In particular, we discuss cell death in the early
      vertebrate embryo, in limb development, and in the nervous system.

PMID- 8522420
TI  - Biochemistry and molecular biology of chromoplast development.
AB  - Plant cells contain a unique class of organelles, designated the plastids, which
      distinguish them from animal cells. According to the largely accepted
      endosymbiotic theory of evolution, plastids are descendants of prokaryotes. This
      process requires several adaptative changes which involve the maintenance and the
      expression of part of the plastid genome, as well as the integration of the
      plastid activity to the cellular metabolism. This is illustrated by the diversity
      of plastids encountered in plant cells. For instance, in tissues undergoing color
      changes, i.e., flowers and fruits, the chromoplasts produce and accumulate excess
      carotenoids. In this paper we attempt to review the basic aspects of chromoplast
      development.

PMID- 8522421
TI  - Sperm-binding proteins.
AB  - Gamete recognition and binding are mediated by specific proteins on the surface
      of the sperm and egg. Identification and characterization of some of these
      proteins from several model systems, particularly mouse and sea urchin, have
      focused interest on the general properties and functions of gamete recognition
      proteins. Sperm-binding proteins located in egg extracellular coats as well as
      sperm-binding proteins that are localized to the egg plasma membrane are
      presented in the context of their structure and function in gamete binding.
      Unifying and disparate characteristics are discussed in light of the diverse
      biology of fertilization among species. Outstanding questions, alternative
      mechanisms and models, and strategies for future work are presented.

PMID- 8522422
TI  - The ultrastructure of epithelial and fiber cells in the crystalline lens.
AB  - Crystalline lenses are often simply described as inside-out stratified epithelial
      like organs composed of uniform (hexagonal cross-section profiles) crescent-like
      cells, arranged end-to-end in concentric shells around a polar axis. In this
      manner, as light is transmitted through lenses, their highly ordered architecture
      contributes to transparency by effectively transforming the multicellular organ
      into a series of coaxial refractive surfaces. This review will attempt to
      demonstrate that such a description seriously understates the structural
      complexity that produces lenses of variable optical quality in different species
      as a function of development, growth, and age. Embryological development of the
      lens occurs in a similar manner in all species. However, the growth patterns and
      effects of aging on lens fibers varies significantly among species. The
      terminally differentiated fiber cells of all lenses are generally hexagonal in
      cross section and crescent shaped along their length. But, while the fibers of
      all lenses are arranged in both highly ordered radial cell columns and concentric
      growth shells, only avian lens fibers are meridian-like, extending from pole to
      pole. In all other species, two types of fibers defined by different shapes are
      continuously formed throughout life. The majority of fibers are s-shaped, with
      ends that do not extend to the poles. Rather, the ends of these fibers are
      arranged as latitudinal arc lengths within and between growth shells. The overlap
      of the ends of specifically defined groups of such fibers constitutes the lens
      suture branches. The location, number, and extent of suture branches within and
      between growth shells are important considerations in lens function because the
      shapes of fiber ends, unlike that along fiber length, are very irregular.
      Consequently, as light is transmitted through sutures, spherical aberration
      (i.e., focal length variation) is increased. The degree of focal length
      variability depends on the arrangement of suture branches within and between
      growth shells, and this architecture varies significantly between species. The
      lifelong production of additional fibers at the circumference of the lens,
      culminating in new growth shells, neither proceeds equally around the lens
      equator, nor features identical fibers formed around the equator. Suture
      formation commences in the inferonasal quadrant, and continues sequentially in
      the superotemporal, inferotemporal, and finally the superonasal quadrants. During
      this process, lens growth produces fibers of specifically defined length and
      shape as a function of their equatorial location.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8522423
TI  - The use of computers in understanding how animal cells crawl.
AB  - Amoeboid cell motility is a complex three-dimensional process which involves
      pseudopod expansion, cellular translocation, and, in some cases, pseudopod
      retraction and complex interactions between the ventral surface of the pseudopod
      and substratum. In order to quantify the basic behavior of amoeboid cells and the
      dynamics of pseudopod extension and retraction, sophisticated two-dimensional and
      three-dimensional computer-assisted motion analysis systems have been developed
      which reconstruct digitized images and compute motility and dynamics morphology
      parameters. These systems provide a wealth of information of how amoeboid cells
      crawl and they have begun to be utilized (1) to elucidate the basic rules of
      amoeboid movement, (2) to identify the behavioral defects of cytoskeletal
      mutants, and (3) to elucidate the mechanism of chemotaxis. In addition, these
      systems represent powerful tools for analyzing the effects of drugs on cell
      behavior, most notably that of white blood cells and neoplastic cells. Since
      computer-assisted motion analysis is a relatively young field, the technologies
      are still evolving and have been underutilized in most areas involving cell
      motility. This review, which includes a description of these technologies and
      examples of their application, will hopefully serve as an impetus for expanded
      use.

PMID- 8522424
TI  - Recurrent laryngeal nerve protection in thyroidectomy.

PMID- 8522425
TI  - Hepatitis C infection among injecting drug users attending the National Drug
      Treatment Centre.
AB  - During a one year period from August 1992 to August 1993, 272 injecting drug
      users attending the National Drug Treatment Centre were tested for antibody to
      Hepatitis C Virus with a second generation EIA test. The overall sero-prevalence
      was 84% (N = 229). A significantly greater proportion of females tested positive
      than males (Female: Male, 94% v 80%, p < 0.012). Looking at sero-prevalence of
      Hepatitis C in relation to duration of intravenous drug misuse, we found that in
      those patients with a duration of misuse of greater than two years (N = 156) the
      sero-prevalence was 95% and in those with a duration of intravenous drug misuse
      of less than two years (N = 116) the sero-prevalence was 70%. We conclude that
      needle sharing continues to occur among injecting drug users during their first
      two years of injecting, despite the existence of harm minimization programmes.
      Our results would suggest that female injecting drug users are involved in
      greater at risk behaviour in relation to Hepatitis C than their male
      counterparts.

PMID- 8522426
TI  - Effect of accommodation of the lens on ocular pressure.

PMID- 8522427
TI  - Comparative antimicrobial activity and spectrum of CP-99,219, a novel
      fluoroquinolone, tested against ciprofloxacin-resistant clinical isolates.
AB  - The fluoroquinolones have an established role in treatment of infection with
      aerobic gram negative rods. The increased importance of gram positive nosocomial
      infection and of acquired fluoroquinolone resistance has stimulated a search for
      new compounds with enhanced potency and spectrum. CP-99,219 is a novel compound
      in this class with enhanced activity against gram positive organisms. We have
      studied the activity of CP-99,219 relative to ciprofloxacin, fleroxacin,
      ofloxacin, and sparfloxacin using test panels of organisms with a high proportion
      of ciprofloxacin resistance. CP-99,219 is more potent than any of the other four
      compounds against both gram positive and gram negative bacteria. The activity of
      CP-99,219 against many bacteria resistant to the established agents, warrants
      further in vitro and clinical studies.

PMID- 8522428
TI  - Progestogens and Cushing's syndrome.
AB  - We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and
      Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused
      clinical hypercortisolism and Cushing's syndrome. Studies of the toxicity of
      Medroxyprogesterone Acetate list the commonest adverse events at 500 mg/day as
      weight gain, water retention, increased blood pressure, tremor, moon face,
      sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid
      like effects are seen in up to 30% of patients treated for longer than 6 weeks
      with mostly large doses of the order of 1500 mg/day but Cushing's syndrome has
      been reported in patients taking 400 mg/day. Neither the glucocorticoid-like
      effects or Cushing's syndrome have been previously observed with Megestrol
      Acetate. In the elderly female population receiving progestogens for neoplastic
      disease the progestogen itself could be an appreciable cause of morbidity both by
      causing glucocorticoid-like effects and Cushing's syndrome but also by lack of
      awareness of the danger of sudden withdrawal of these compounds when the
      hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms
      could be easily overlooked unless appropriate testing for Cushing's syndrome is
      carried out. While the progestogen may have to be continued indefinitely a dose
      decrease may be feasible with reduction of morbidity.

PMID- 8522429
TI  - Emergency primary coronary angioplasty in patients with acute myocardial
      infarction who are unsuitable for intravenous thrombolysis.
AB  - Intravenous thrombolytic therapy is now accepted as the standard method of
      achieving coronary reperfusion in patients with acute myocardial infarction.
      There are several important limitations. Primary percutaneous transluminal
      coronary angioplasty is an attractive method for reopening occluded coronary
      arteries. Between 1986 and 1993, 14 patients in whom there was an absolute
      contraindication to thrombolysis underwent emergency coronary angioplasty as the
      primary treatment for acute myocardial infarction. Coronary artery patency was
      restored in 13/14 (93%). One patient died in hospital. The median follow-up was
      one year. One patient suffered a further myocardial infarction and one patient
      required coronary artery bypass surgery at follow-up. Emergency coronary
      angioplasty services should be developed to treat those patients in whom there is
      a contraindication to thromboloysis.

PMID- 8522430
TI  - Primary aldosteronism in pregnancy--should it be treated surgically?
AB  - We report a case of primary aldosteronism in pregnancy that was treated
      surgically by removal of the adenoma in the 2nd trimester. Only a few cases have
      been reported in the English literature due to the rarity of the condition.
      Primary aldosteronism follows a variable course in pregnancy. In the majority of
      cases the hypertension and hypokalaemia are made worse, necessitating
      antihypertensive medication to control the blood pressure. Some of the drugs
      required for treatment are known to affect the fetus. In a minority of cases the
      hypertension improves with pregnancy. This is thought to be due to the high
      levels of progesterone which is an aldosterone antagonist. Primary aldosteronism
      invariably gets worse in the post partum period, irrespective of the antenatal
      course of the disease. Surgery seems to be the treatment of choice for this
      condition, provided the adenoma is localised. It has the advantage of offering an
      immediate solution, avoids fetal complications of medical treatment and possible
      deterioration in the post partum period.

PMID- 8522431
TI  - Influences on breast feeding initiation and duration.
AB  - The study objectives were to establish the prevalence of breast feeding at birth,
      at four and twelve weeks after birth and describe the factors associated with its
      initiation and duration. The study population consisted of all babies born in May
      1993 (n = 162) to mothers resident in Kildare. The response rate was 145/162 (89
      percent). Mothers were visited within fourteen days of the birth. Breast feeding
      mothers were re-visited when the baby was four to six weeks old and at twelve to
      fourteen weeks. Interviews were conducted using an interviewer administered
      questionnaire. Fifty-five mothers (38%) chose to breast feed at birth. Twelve
      (8%) had stopped by the first, ten (7%) by the second and fourteen (10%) by the
      third visit. Higher social class and maternal grandmother having breast fed were
      significantly associated with initiation (p < 0.05 and p < 0.0005 respectively).
      Smokers and non-working mothers were significantly less likely to breast feed and
      smokers had a significantly shorter duration of breast feeding but these
      associations disappeared on social class adjustment.

PMID- 8522432
TI  - Acute haematogenous osteomyelitis--evaluation of management in the 1990s.
AB  - There are three main areas of debate in the management of acute haematogenous
      osteomyelitis: The value of early operative intervention, the duration and route
      of antibiotic treatment and the choice of antibiotic therapy. The aim of this
      study is to evaluate the management protocol of acute haematogenous osteomyelitis
      as used in The Childrens' Hospital, Temple Street. The protocol can be
      recommended. Absence of pyrexia and a normal Erythrocyte Sedimentation Rate do
      not exclude acute haematogenous osteomyelitis. Current thoughts on antimicrobial
      therapy are presented.

PMID- 8522433
TI  - Comparison of two fluorescent probes for the measurement of erythrocyte membrane
      fluidity in renal dialysis patients.
AB  - Two fluorescent probes were used for the measurement of membrane fluidity in
      patients on haemodialysis and continuous ambulatory peritoneal dialysis. 1,6
      Diphenyl-1,3,5-hexatriene (DPH) anisotropy gives an indication of lipid order and
      pyrene measures lateral diffusion through the membrane. Pyrene dimer/monomer
      ratio was significantly lower than controls in both pre-dialysis and post
      dialysis samples but DPH anisotropy was unchanged. Both methods showed an
      increase in membrane fluidity across a 4 hour haemodialysis session. There was an
      increase in membrane fluidity in CAPD patient samples which was more marked using
      DPH than pyrene. These results suggest that the two probes give different but
      complementary information about changes in membrane fluidity and may be more
      informative when used together rather than singly.

PMID- 8522434
TI  - Clear cell sarcoma of the kidney in an adult.
AB  - An adult case of clear cell sarcoma of the kidney is described. The clinical,
      histological, immunohistochemical and electron microscopical features of the
      tumour are described.

PMID- 8522435
TI  - Giant ganglion of the proximal tibiofibular joint: a case report.
AB  - Ganglions of the tibiofibular joint are a rare condition. The exact tissue of
      origin could not be accurately determined despite the use of CAT scanning. At
      surgery a giant ganglion of the tibiofibular joint was resected with preservation
      of the peroneal nerve.

PMID- 8522436
TI  - Adverse aspects of small thyroid cancer and need for treatment.
AB  - BACKGROUND: Small, well-differentiated thyroid cancer (tumor < 1.5 cm) is
      frequently dismissed as biologically inconsequential, although varied reports
      have offered differing experiences. METHODS: A total of 382 thyroid cancer
      patients were reviewed. Of these, 99 patients had tumors that were < or = 1.5 cm.
      Thirty-five patients in this group with positive nodes, extrathyroidal invasion,
      or metastatic disease were studied. RESULTS: Thirty-five patients (one-third of
      the < 1.5 cm group) showed other sites of involvement: nodes, 28; lung, 1;
      muscle, 7; nerve, 5; and bone, 2. Six patients had residual cancer following
      surgery. Surgery included thyroidectomy and neck dissection as well as orthopedic
      procedures for metastatic bone disease. Radioiodine ablation was used in 33
      patients, external radiation in 5. Thirty-one patients are well without disease,
      3 are alive with disease, 1 died of disease. CONCLUSIONS: Small, well
      differentiated thyroid cancer is infrequently aggressive, but it may be a source
      for metastatic morbidity and recurrence and can be viewed as potentially lethal.
      Need for treatment should not be ignored based solely on the size of the tumor.

PMID- 8522437
TI  - Epilarynx: pharynx or larynx?
AB  - BACKGROUND: As a general rule, epilarynx is studied as a part of supraglottis. On
      the contrary, in France, due to its particular natural history, it is often
      studied separately. METHODS: To assess the value of this French classification,
      we compared from an epidemiologic point of view, in one study, 86 cases of
      epilarynx squamous cell carcinoma (SCC) with 431 oropharynx, 339 hypopharynx, and
      89 vestibule SCC. In another study, we compared, from a clinical point of view,
      232 epilarynx SCC with 1351 oropharynx, 652 hypopharynx, and 372 vestibule SCC.
      RESULTS: Epilarynx patients appeared to be much heavier drinkers than larynx
      patients and similar to pharynx patients but tobacco consumption did not differ.
      The patterns of nodal involvement were similar for pharynx and epilarynx SCC. For
      stages I and II, patterns of failures were similar, but for stages III and IV,
      there were fewer locoregional failures in vestibule patients; distant metastases
      were equally frequent for these tumors. From the standpoint of multiple
      primaries, epilarynx SCC appeared to be more akin to pharynx than to larynx SCC
      with a much lower incidence of lung cancers. Finally, the outcome after treatment
      was different for vestibule, epilarynx, and pharynx SCC, with a 5-year survival
      of 43%, 27%, and 13%, respectively. CONCLUSIONS: These data support the
      identification of epilarynx as a real entity that should be taken into account
      for stratification in clinical trials.

PMID- 8522438
TI  - Outcome analysis of Zenker's diverticulectomy and cricopharyngeal myotomy.
AB  - BACKGROUND: The optimal management of Zenker's diverticula is controversial in
      part because of the method of categorizing treatment success or failure.
      Subjective and objective radiologic tests have been used to evaluate the various
      treatment modalities. There seems to be poor correlation between subjective and
      objective findings, and we tested this hypothesis in a group of patients
      undergoing one form of therapy (diverticulectomy and cricopharyngeal myotomy
      [CPM]). METHODS: Eighteen consecutive patients underwent Zenker's
      diverticulectomy and CPM. Postoperative symptoms and abnormalities detected by
      barium esophagrams were evaluated after a mean follow-up of 30.3 months (range, 7
      74 months). RESULTS: Three of 18 patients (17%) complained of dysphagia (2
      occasional and not bothersome; 1 bothersome and affecting dietary intake).
      Postoperative static contrast esophagrams were interpreted without knowledge of
      the subjective symptoms. Small diverticula were identified in 8 patients (44%).
      There was poor correlation between symptoms and objective radiographic
      abnormalities with agreement of 56% and a kappa statistic of 0.23. CONCLUSIONS:
      Objective radiographic abnormalities are far more common than subjective
      complaints following diverticulectomy and CPM. Postoperative static contrast
      radiography is not routinely required and may be misleading because of the poor
      correlation between symptoms and radiographic findings. The value of dynamic
      videofluoroscopy needs to be evaluated.

PMID- 8522439
TI  - Maneuver to assist examination of the hypopharynx.
AB  - BACKGROUND: The lower hypopharynx, lying posterior to the larynx, is not usually
      assessable during outpatient examination. A maneuver was developed to assist
      flexible endoscopic examination of this region. The discomfort experienced by
      fifty consecutive patients undergoing the maneuver was assessed together with the
      view obtained. METHOD: Fifty patients assigned scores from 0 to 10 to the
      discomfort experienced during manual anterosuperior traction applied to the
      prelaryngeal skin, together with two other commonly performed procedures. The
      view obtained in the last 30 patients was assessed. RESULTS: The mean discomfort
      score for the maneuver was 3.77, compared with 3.84 and 5.94 for the other two
      procedures. A view to the cricoarytenoid joint or below was obtained in 60% of
      the patients assessed. CONCLUSIONS: We conclude that the maneuver is well
      tolerated and results in a useful view of the hypopharynx in the majority of
      patients. No prior report of this maneuver has been found in the literature.

PMID- 8522440
TI  - Timing of glottic closure during normal swallow.
AB  - BACKGROUND: The purpose of this study was to determine the temporal
      characteristics and patterns of glottic closure during normal swallow using
      concurrent videofluoroscopy and videoendoscopy. METHODS: Three swallows each of
      four bolus types were examined in eight healthy volunteers with the endoscope in
      two positions: at the level of the uvula and at the laryngeal vestibule. Data
      analysis compared: (1) temporal relationships between laryngeal behaviors and
      oropharyngeal swallow events and (2) airway conditions at the time of key
      oropharyngeal events. RESULTS: Although arytenoid adduction and subsequent
      arytenoid contact occurred as one of the initial events during swallow, the
      timing of these events was highly variable. On the other hand, true vocal cord
      (TVC) closure occurred mainly after the onset of laryngeal elevation, and it was
      affected by bolus volume. CONCLUSIONS: In normal swallow, arytenoid closure did
      not always mean complete TVC closure, and complete TVC closure might be
      accomplished during the process of laryngeal elevation and arytenoid tilting.

PMID- 8522441
TI  - Mortality in the pediatric patient with tracheotomy.
AB  - BACKGROUND: The mortality rate of children with tracheotomies is estimated to be
      between 11% and 40%, although the incidence of tracheotomy-related deaths is only
      between 0% and 3.4%. The purpose of this report was to analyze the mortality rate
      in children with tracheotomies. METHODS: A review of the medical records of
      children at the University of Iowa Hospitals and Clinics who underwent
      tracheotomy over a 15-year period ending in 1989 was performed. Data were
      analyzed in 5-year time blocks (Block 1, 1975 to 1979; Block 2, 1980 to 1984; and
      Block 3, 1985 to 1989). RESULTS: Fifty-two patients died with tracheotomy tubes
      in place. In 4 patients, the cause of death was tracheotomy related. Three of
      these patients were under 5 years of age and died secondary to tracheotomy tube
      displacement or obstruction; one patient, an 18-year-old, developed a fatal
      tracheotomy-related vascular hemorrhage. The average age of patients who died
      with tracheotomies decreased significantly from Block 1 to Block 3; in Block 3,
      mean age at the time of tracheotomy was significantly lower in patients who died
      than in patients who survived. A comorbidity score (CS) based on the number of
      airway diagnoses showed that higher CSs were associated with a poorer prognosis.
      CONCLUSIONS: Mortality does not seem to be strongly related to the presence of
      the tracheotomy tube. Overall, two diagnostic groups were found to be
      independently associated with a poorer prognosis, ie, mechanical ventilation and
      pulmonary disease. Tracheotomies performed to provide airway access during other
      surgical procedures were associated with a better prognosis.

PMID- 8522442
TI  - Thorascopic staging of stomal recurrence.
AB  - BACKGROUND: Squamous cell carcinoma of the low cervical area may be secondary to
      stomal recurrence following laryngectomy, low cervical esophageal disease, or
      peritracheal metastasis. Most often patients with disease in this area have
      already received both surgery and radiotherapy. Prior to Sisson's description of
      the trans-sternal radical neck dissection or mediastinal dissection the
      management and prognosis was uniformly poor. Since then, a number of authors have
      reported their experience with mediastinal dissection. Survival remains poor but
      palliation has been acceptable. Unfortunately, resectability of the disease
      cannot often be determined prior to the actual surgical procedure. A number of
      patients are explored only to have the procedure terminated. Thoracoscopy is a
      procedure that involves insertion of two or three trocars into the right thoracic
      cavity with collapse of the right lung. A form of endoscopic surgery, it permits
      visualization and dissection of the important structures of the mediastinum.
      Tracheal, esophageal, and great vessel invasion by tumor can be evaluated.
      METHODS: Prospectively, all patients initially seen with stomal recurrence from
      1991 to 1994 were evaluated. CT scans, MRIs as well as thoracoscopy were
      performed when indicated. RESULTS: One patient required conversion to a
      minithoracotomy involving a 7-cm chest incision. The patient was found to have
      unresectable disease with tumor involving the great vessels of the mediastinum. A
      second patient was found to have unresectable disease with tumor encasing the
      subclavian artery. The third patient was found to have no mediastinum
      involvement. The patient with no mediastinum involvement underwent a stomal
      resection with mediastinal dissection. Reconstruction with a pectoralis major
      myogenous flap was performed. The patient has remained disease free to date. The
      remaining two patients were judged to have unresectable disease and were offered
      palliative treatment. Both of these patients died of the disease within 6 months.
      CONCLUSIONS: Thoracoscopy provides important information in judging the surgical
      resectability of patients with stomal recurrence. This procedure has not been
      previously described in the otolaryngologic literature. We provide some
      suggestions for its use in the evaluation of the mediastinal extent of disease.

PMID- 8522443
TI  - Composite mucochondral flap for repair of cerebrospinal fluid leaks.
AB  - BACKGROUND: Cerebrospinal fluid leaks from defects in the anterior cranial fossa
      present a difficult management problem. Particularly when the defects are large,
      conventional techniques may not be sufficient to close them. We describe a new
      technique for treating such CSF leaks using a composite mucochondral flap from
      the nasal septum. METHODS: We treated five patients with the composite
      mucochondral flap. All patients were women aged 29-60 years. Two patients had an
      encephalocele, one had an esthesioneuroblastoma, and one had adenocarcinoma; one
      leak was spontaneous. RESULTS: The CSF leak was successfully closed in all five
      patients. No patients have experienced recurrence; the longest follow-up has been
      39 months. The donor site on the septum healed without complication in all
      patients. CONCLUSIONS: The composite flap is useful for repairing large defects
      or after radiotherapy or trauma. The advantage of skeletal support to counter the
      pressure exerted by CSF seems clear.

PMID- 8522444
TI  - Cost-benefit management decisions for carcinoma of the retromolar trigone.

PMID- 8522445
TI  - Paget's sarcoma of the mandible.
AB  - BACKGROUND: Sarcomatous change occurs in less than 1% of patients with Paget's
      disease. It has been reported in only 9 patients in the mandible, and has been
      uniformly fatal. Comparison of Paget's sarcoma of the mandible to osteosarcoma of
      the mandible and to osteosarcoma in other locations was made to attempt to
      explain and improve the outcome of patients with these tumors. METHODS: Two 78
      year-old women with Paget's sarcoma of the mandible treated with radical
      resection are reported. The literature is reviewed to compare the clinical
      presentation and prognosis of patients with mandibular Paget's sarcoma to
      patients with osteosarcoma in non-Pagetoid mandibles and with osteosarcoma
      outside of the head and neck. RESULTS: Both patients died within 2 years of lung
      metastases. The patients with mandibular Paget's sarcoma were markedly older,
      with an average age of 65.6 years, compared to 32.5 years for mandibular
      osteosarcoma. Paget's sarcoma of the mandible was uniformly rapidly fatal; in non
      Pagetoid mandibles the 5-year survival is 40%. There have been reports of only 7
      patients who have survived with Paget's sarcoma in other locations. In
      osteosarcoma of the extremities 5-year disease-free survival exceeds 75% with
      multimodality therapy. CONCLUSIONS: Paget's sarcoma of the mandible is a rare
      tumor which affects elderly patients. It progresses rapidly and has a much poorer
      prognosis than osteosarcoma occurring in a non-Pagetoid mandible. The prognosis
      may be improved with early detection and treatment with multimodality therapy.

PMID- 8522446
TI  - Elevated carcinoembryonic antigen levels correlating with disease recurrence in a
      patient with adenoid cystic carcinoma.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) is an oncofetal glycoprotein involved
      in cell recognition and adhesion. Serum CEA has been extensively studied as a
      potential chemical marker for malignancy, most notably in patients with colon
      carcinoma. Serum CEA measurements have not been reported for patients with
      salivary gland carcinomas. METHODS: Serum CEA was measured in a case study using
      enzyme immunoassay with monoclonal antibody specific for CEA. Tissue was examined
      with standard histologic and immunohistologic methods. RESULTS: A patient was
      initially seen with adenoid cystic carcinoma (ACC) of the trachea and had a
      markedly elevated serum CEA level which declined after surgical resection. The
      serum CEA level became elevated again when the patient developed abdominal
      metastases and then declined after debulking of the tumor. Immunohistochemical
      study of the tumor was positive for CEA. CONCLUSIONS: The measurement of serum
      CEA levels may play a role in the management of patients with ACC. Clinical
      investigation utilizing monoclonal antibodies against CEA, for imaging and for
      the delivery of chemotherapy and radiotherapy may be worthwhile.

PMID- 8522447
TI  - Histologic variant of the epithelial-myoepithelial carcinoma of the salivary
      gland: a case report.
AB  - BACKGROUND: Epithelial-myoepithelial carcinoma (EMC) of the salivary gland is a
      low-grade carcinoma. It has been widely accepted as a clinicopathologic entity
      only in the past decade. Histologically, the classical bimodal differentiation of
      inner eosinophilic ductal cells and outer layer of clear myoepithelial cells has
      been well documented by many authors. However, the proportion of each component
      may vary in different tumors or within the same tumor, and different histologic
      patterns have been described. The clinicopathologic findings of an epithelial
      myoepithelial carcinoma of the parotid gland in a 73-year-old man are presented.
      METHODS: Light microscopy including immunohistochemistry and ultrastructural
      studies were done. RESULTS: The various histologic patterns and bimodal
      differentiation of the tumor were noted. CONCLUSIONS: The present case
      demonstrates the myriad of histologic patterns that can occur in epithelial
      myoepithelial carcinoma. Differentiation from malignant mixed tumor is essential
      and possible. The importance of the awareness of its histologic variants is
      emphasized.

PMID- 8522448
TI  - Lymphoepithelial carcinoma of the parotid gland.
AB  - BACKGROUND: Primary lymphoepithelial carcinoma of the parotid gland is a rare
      tumor with an increased incidence among Eskimos and Orientals. We reviewed our
      experience with parotid lymphoepithelial carcinoma and investigated its
      pathophysiology and possible association with Epstein-Barr virus. METHODS: We
      performed a retrospective review of records of patients diagnosed with
      lymphoepithelial carcinoma of the parotid gland. RESULTS: We identified two women
      of Hispanic origin diagnosed with primary lymphoepithelial carcinoma of the
      parotid gland. In one of the cases, the carcinoma was intimately associated with
      a benign lymphoepithelial lesion. In both cases, there was no demonstration of
      Epstein-Barr virus. CONCLUSION: Primary lymphoepithelial carcinoma of the parotid
      gland may arise from malignant transformation of a benign lymphoepithelial
      lesion.

PMID- 8522449
TI  - Detection of panel-reactive anti-HLA class I antibodies by enzyme-linked
      immunosorbent assay or lymphocytotoxicity. Results of a blinded, controlled
      multicenter study.
AB  - A soluble HLA ELISA for the detection of anti-HLA class I IgG antibodies was
      developed and compared to complement-dependent microlymphocytotoxicity. ELISA
      plates were coated with a panel of sHLA class I antigens isolated from the
      culture supernatants of 46 different EBV-transformed phenotyped B-cell lines.
      After the incubation of the coated plates with test serum, bound antibodies were
      detected using a peroxidase-conjugated anti-human IgG antibody. Absorbance was
      read using an ELISA plate reader and assay results were analyzed by computer.
      Antibody specificities were determined by Fisher's exact test tail analysis. The
      reproducibility of ELISA assay results was evaluated in a blinded, controlled
      multicenter study. A total of 102 serum specimens from patients on waiting lists
      to receive kidney transplants were tested five times by ELISA in five different
      laboratories. The correlation coefficients (r) of %PRA values determined by ELISA
      ranged from 0.89 to 0.96, and the average agreement on qualitative assay results
      (antibody positive vs antibody negative) was 98%. Endpoint titration of several
      serum specimens demonstrated equivalent sensitivity of ELISA and
      microlymphocytotoxicity (using the anti-globulin antibody protocol). Most of the
      antibody specificities determined by ELISA were in agreement with specificities
      determined by microlymphocytotoxicity. To evaluate the correlation of ELISA and
      microlymphocytotoxicity (CDC) assay results the same 102 specimens were tested
      six times by CDC in five different laboratories. The interlaboratory correlation
      coefficient (r) of %PRA values determined by microlymphocytotoxicity ranged from
      0.57 to 0.94, and the average agreement on qualitative assay results was 85%. A
      comparison of ELISA with microlymphocytotoxicity was performed using consensus
      microlymphocytotoxicity results. This showed a high correlation (r = 0.81) of
      %PRA values determined by ELISA and microlymphocytotoxicity. This demonstrates
      that the detection of anti-HLA class I antibodies by soluble HLA ELISA is a
      reliable alternative to microlymphocytotoxicity testing.

PMID- 8522450
TI  - Updated characterization of ancestral haplotypes using the Fourth Asia-Oceania
      Histocompatibility Workshop panel.

PMID- 8522451
TI  - A subset of HLA-DR9 molecules is detected by a polymorphic monoclonal antibody on
      lymphoblastoid cell lines but not on peripheral blood lymphocytes.
AB  - Some mAbs recognizing polymorphic epitopes of HLA-DR molecules exhibit striking
      differences of reactivity with the same HLA-DR molecules expressed by different
      cell types. In this study, we investigated the basis for the differential
      reactivity of the polymorphic anti-DR mAb OHA TM901 with HLA-DR9 molecules
      expressed by human PBLs or LCLs. By immunoprecipitation experiments we showed
      that OHA TM901 recognizes a subset of HLA-DR9 molecules from LCLs. This subset
      corresponds to HLA-DR9 molecules containing immature-type oligosaccharides. The
      absence of OHA TM901 reactivity with HLA-DR9 PBLs, as revealed by cytofluorometry
      analysis, suggests that this subset is either not expressed or expressed at a
      very low level on PBLs. These results indicate that overexpression of HLA-DR
      molecules in immortalized LCLs could lead to cell-surface expression of
      underglycosylated forms which are generally not found on the cell surface of
      PBLs.

PMID- 8522452
TI  - Molecular analysis of T cell repertoires. Spectratypes generated by multiplex
      polymerase chain reaction and evaluated by radioactivity or fluorescence.
AB  - The analysis of T-cell repertoires has been facilitated by the introduction of
      methods in which the length heterogeneity of the third complementarity region
      (CDR3) is used to further refine V-family-specific PCR. We call our
      implementation of this technique T-cell spectratyping. This method is especially
      important in analysis of specific expansion or retention of T cells in human
      immune system function. Current methodologies are cumbersome in the number of PCR
      reactions and gels needed for complete analysis of TCR BV repertoires. We
      describe here the optimized conditions for using 11 TCR BV primer pairs in
      multiplex PCR which allow for a more compact analysis. In addition, the two
      primers act as controls for each other in the PCR. The use of these primers is
      shown using either fluorescent or radiolabeled constant primers. The two labeling
      methods give comparable results. Fluorescent primers avoid the difficulties
      associated with use of radioactivity. Autoradiography with 32P-labeled primers is
      simpler, requiring less instrumentation.

PMID- 8522453
TI  - Defining the allelic variants of HLA-A30 in the Sardinian population using
      amplification refractory mutation system--polymerase chain reaction.
AB  - HLA-A30 is present in the Sardinian population at a frequency of 23%. We have
      designed a system using nested ARMS-PCR to determine the relative frequencies of
      the HLA-A*30 allelic variants (A*3001, A*3002, and A*3003) within this
      population. The use of a nested PCR approach, in which the first-round reaction
      provides HLA-A*30 specificity and template DNA for the subsequent nested
      reactions, is a powerful means of discriminating between alleles of very similar
      sequence. Using this method, we performed subtyping of 35 serologically defined
      HLA-A30 Sardinian individuals, and taking into account homozygotes, identified 38
      A*30 alleles. Of these, 33 typed as A*3002, four typed as A*3001, and one sample
      did not conform to the patterns of reactivity of any of the published A*30
      alleles. Haplotype information showed strong linkage disequilibrium between
      A*3002 and B18. This study underlines the potential of DNA-based methods for
      typing HLA class I in terms of adding further levels of definition to studies of
      population structure and also as a means of identifying new alleles.

PMID- 8522454
TI  - Cytolytic T lymphocytes from human renal allograft biopsies are tissue specific.
AB  - The cytolytic activity of T lymphocytes infiltrating renal allografts from
      recipients undergoing episodes of acute cellular rejection was studied. These T
      cell populations, composed of both CD4+ and CD8+ cells, demonstrated significant
      cytolytic activity against both donor-derived KCLs and B-LCLs. In five of 21
      biopsy-derived lines greater cytolytic activity was measured against donor KCLs
      compared to donor B-LCLs, suggesting the presence of kidney antigen-specific, MHC
      restricted clones. Clones developed by stimulation with donor B-LCLs lysed both
      donor B-LCLs and KCLs while clones developed on donor KCLs as stimulator cells
      showed tissue specificity. Three of 26 clones recognized tissue-specific antigens
      in the context of donor MHC class I antigens lysing donor KCLs but not B-LCLs.
      These data demonstrate that a subpopulation of T cells recognizing kidney
      specific antigens are present in biopsies of renal allograft recipients
      undergoing acute cellular rejection. This subpopulation of tissue-specific
      cytotoxic T lymphocytes may prove to contribute significantly to the pathology of
      allograft rejection.

PMID- 8522455
TI  - CD8+ lymphocytes that kill allogeneic and xenogeneic major histocompatibility
      complex class I targets.
AB  - CD8+ CTLs generated in a two-way MLR should lyse target cells only if these
      targets share a class I MHC allele with the original stimulators. Using cattle
      PBMCs in a two-way MLR, we generated CD8+ CTLs that kill allogeneic and
      xenogeneic cell lines. We have named these cells MLK cells. PBMCs isolated from
      two unrelated animals were cultured together. After 14 days microfluorimetry
      analysis was performed on the MLK cells with results showing > 90% CD8+ cells.
      RFLP analysis revealed these cells to be predominately of one animal. MLK cells
      were then used as effector cells in cytotoxicity assays with syngeneic,
      allogeneic, and xenogeneic target cells. MLK cells were able to kill all targets.
      Incubating MLK cells with mAbs to CD8 markedly reduced killing, suggesting a TCR
      mediated cytolytic pathway. Effective cytolysis of these targets by MLK cells was
      dependent on class I expression. MHC class I expression-impaired mutants of
      allogeneic and xenogeneic targets were not susceptible to cytolysis. Comparisons
      to LAK cells revealed similarities in phenotype and function to the NK1.1-, CD8+
      subset.

PMID- 8522456
TI  - HLA and elephantiasis in lymphatic filariasis.
AB  - Lymphatic filariasis presents a spectrum of manifestations with infection-free
      asymptomatics at one end and elephantiasis at the other. In order to determine if
      any HLA antigens are associated with the development of elephantiasis, we
      compared the HLA frequencies in 55 elephantiasis patients with those in 40
      controls consisting of individuals older than 45 years of age without any signs
      of elephantiasis. The only significant difference in class I antigen frequencies
      was observed for B27, which was present in 11% of the patients and absent in the
      controls. More differences were observed in HLA class II antigen frequencies.
      Both DR3 and the 2B3 epitope (on DQ6, DQ8, and DQ9 molecules) were significantly
      decreased in patients with elephantiasis whereas the DQ5 frequency was
      significantly higher in patients than in controls. Analysis of specific antibody
      isotype profiles revealed that DQ5-positive individuals had increased levels of
      antifilarial IgG3, an isotype known to be involved in tissue damage. These data
      suggest that HLA class II genes may control the course of Brugian filariasis by
      influencing the T-cell-dependent antibody repertoire.

PMID- 8522457
TI  - Vancomycin administration and monitoring reappraisal.

PMID- 8522458
TI  - Antibiotics and the expression of staphylococcal virulence.
AB  - The last 25 years have witnessed a continuing interest in staphylococci as causes
      of human infection even though over 100 years have elapsed since their discovery.
      This has been due in part to the recognition of new disease entities such as
      scalded skin syndrome, toxic shock syndrome and various infections due to
      coagulase-negative staphylococci. Development of antimicrobial agents has not
      solved the problem of these infections partly because of their mediation by novel
      toxins and partly due to the emergence of multiple drug resistance. However study
      of the interaction between certain antibiotics and staphylococci in vitro and in
      vivo has provided new knowledge concerning the role of cell wall-associated and
      soluble virulence factors in the pathogenesis of staphylococcal disease.

PMID- 8522459
TI  - Antibacterial properties of AM-1155, a new 8-methoxy quinolone.
AB  - AM-1155 is a new 8-methoxy quinolonecarboxylic acid with a broad spectrum of
      antibacterial activity. It inhibited more than 90% of clinical isolates of
      methicillin-susceptible Staphylococcus aureus, streptococci, Enterococcus
      faecalis, most of the Enterobacteriaceae, Acinetobacter calcoaceticus and
      Haemophilus influenzae at the concentration of 0.39 mg/L. AM-1155 was 2- to 16
      fold more active than ciprofloxacin against Gram-positive organisms including
      methicillin-resistant staphylococci. The antibacterial activity of AM-1155 was
      almost equal to that of sparfloxacin against a wide range of Gram-positive and
      Gram-negative species. AM-1155 also showed a good activity against anaerobes. The
      protective efficacy of AM-1155 against experimental systemic infections with Gram
      positive and Gram-negative pathogens in mice was almost equal or superior to that
      of sparfloxacin. AM-1155 was 5- to 28-times more effective than ciprofloxacin, in
      terms of ED50 at one week, in staphylococcal and streptococcal infections.

PMID- 8522460
TI  - Real-time measurement of cell permeabilization with low-molecular-weight
      membranolytic agents.
AB  - A new method for studying the action of membranolytic agents by simple
      measurement of light emitted from cells is described. It is based on the
      expression of the click beetle (Pyrophorus plagiophthalamus) luciferase gene
      (lucGR) in Escherichia coli, Bacillus subtilis and Spodoptera frugiperda cells in
      order to make them bioluminescent. The diffusion of the substrate for luciferase
      enzyme through the cell membranes is very low at physiological pH, and therefore
      a change in membrane permeability is seen as a change of in-vivo luminescence of
      cells. The cells used in this study represent different membrane structures, and
      thus allow a comparison of the reactions of the different membranes towards
      membranolytic agents in a real-time measurement. The dose-response data
      correlated well with target cell viable count. In addition, the time course of
      light emission as a consequence of permeabilizing compound is dose-dependent. The
      action of the compounds on prokaryotic and eukaryotic cells was found to be
      highly dependent on the permeabilizer used.

PMID- 8522461
TI  - Growth temperature-dependent variation of cell envelope lipids and antibiotic
      susceptibility in Stenotrophomonas (Xanthomonas) maltophilia.
AB  - Clinical isolates of Stenotrophomonas (Xanthomonas) maltophilia showed growth
      temperature-dependent variation in susceptibility (TDVS) to aminoglycoside
      antibiotics between 30 degrees C and 37 degrees C, but little or no TDVS effect
      for polymixin B, colistin, ceftazidime, chloramphenicol and piperacillin. When
      phenylethanol was added at sub-inhibitory concentrations, the TDVS effect was
      eliminated. Gas liquid chromatography showed that 13-methyl tetradecanoate (i
      15;0), was the predominant fatty acid, and was present in lower proportions in
      cells grown at 30 degrees C than 37 degrees C, by contrast to the unsaturated
      acids, which were found in increased proportions in cells grown at 30 degrees C.
      However, the extent of these shifts in composition did not correlate with the
      extent of the TDVS effect in individual strains. Membrane analysis by spin label
      electron spin resonance spectroscopy showed that strains exhibiting TDVS had
      significantly decreased membrane fluidity compared with susceptible strains at 30
      degrees C. Furthermore, analysis of the outer and cytoplasmic membranes from the
      strains with TDVS revealed that in organisms grown at 30 degrees C, the outer
      membrane remained in a more rigid conformation than the cytoplasmic membrane. We
      conclude that resistance of S. maltophilia to aminoglycoside antibiotics at 30
      degrees C correlates with changes in the conformation of the outer membrane so
      that binding and/or uptake of the antibiotic is inhibited.

PMID- 8522462
TI  - In-vitro inhibitory activity of gamma-linolenic acid on Escherichia coli strains
      and its influence on their susceptibilities to various antimicrobial agents.
AB  - Recent experimental evidence implies that polyunsaturated fatty acids (PUFAs)
      possess anti-infective activity which is unrelated to any alteration of
      eicosanoid biosynthesis or cytokine production provoked by PUFAs and it seems
      necessary to establish their possible influence on Gram-negative bacteria. Forty
      two Escherichia coli strains were cultured in vitro in the presence of gamma
      linolenic acid (GLA) at concentrations of 50 mg/L and 300 mg/L and a total of 77
      killing curves were performed with GLA concentrations of 100, 200 and 300 mg/L
      GLA. At 50 and 300 mg/L, GLA inhibited 9.5% and 33.3% of strains respectively;
      GLA killing curves demonstrated a > or = 1 log GLA inhibitory effect in 0%, 18.2%
      and 72.7% of strains after the 5 h sequential exposures at 100, 200 and 300 mg/L
      GLA but this was not observed after the 24 h GLA exposure. Following removal of
      the E. coli strains from the culture medium with GLA, > or = four-fold increases
      in MICs and/or MBCs of various antimicrobials, were observed in 42.9% and 60% of
      strains after exposure to 50 and 300 mg/L GLA respectively; most of these
      increases involved aminoglycosides. The reproducibility of GLA inhibitory effects
      and increase in MICs and/or MBCs for E. coli in the two different experimental
      procedures used, was 82% and 73% respectively. Further studies are necessary to
      clarify the mechanism of GLA action on E. coli and assess the clinical relevance
      of these findings.

PMID- 8522463
TI  - Imipenem resistance in clinical isolates of Proteus mirabilis associated with
      alterations in penicillin-binding proteins.
AB  - Two strains of Proteus mirabilis, IpR1 and IpR2, resistant to both imipenem and
      mecillinam, but susceptible to other beta-lactams were isolated from blood
      cultures of patients who had been treated with imipenem. Strain IpR1 was isolated
      in the same sample as a P. mirabilis IpS1 which was susceptible to imipenem and
      mecillinam. Strains IpR1 and IpR2 did not produce a beta-lactamase and their
      outer membrane protein profiles were similar to those of IpS1 and P. mirabilis
      ATCC 29906. Electrophoretic profiles of penicillin-binding proteins (PBPs) showed
      a decrease in PBP 1A of strains IpR1 and IpR2 compared with IpS1 and ATCC 29906.
      Competition experiments revealed a decrease in affinity of PBP 2 for imipenem
      from strain IpR1. These findings suggest that imipenem resistance in P. mirabilis
      might result from altered PBPs, as reported for Acinetobacter baumanii and
      Pseudomonas aeruginosa.

PMID- 8522464
TI  - Emergence of bacterial resistance to imipenem and ciprofloxacin in a university
      hospital.
AB  - We have continuously monitored the in-vitro activities of imipenem and
      ciprofloxacin against large numbers of non-fastidious clinical isolates. After
      eight years of use, 97-100% of Enterobacteriaceae and Acinetobacter baumannii
      remained susceptible to imipenem, but susceptibility of Pseudomonas aeruginosa
      declined from 100% to 91%. After six years of use, 94%-100% of Enterobacteriaceae
      (except Providencia stuartii) remained susceptible to ciprofloxacin but
      susceptibility of P. stuartii, A. baumannii and P. aeruginosa declined from 100%
      to 46%, 66% and 84%, respectively. Oxacillin-resistant staphylococci were
      considered to be resistant to imipenem and all beta-lactams. There were no
      quinolone-resistant staphylococci observed in 1986, but susceptibilities of
      Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus
      to ciprofloxacin decreased to 85-93% for oxacillin-susceptible strains and to 7
      39% for oxacillin-resistant strains. Enterococcus faecalis has remained
      susceptible to imipenem and the modal MIC of ciprofloxacin has remained 1 mg/L;
      however, susceptibility to ciprofloxacin 2 mg/L decreased from 94% to 64%.
      Imipenem-quinolone cross-resistance was observed for staphylococci but not for P.
      aeruginosa.

PMID- 8522465
TI  - In-vitro and intracellular activity of rifabutin on drug-susceptible and multiple
      drug-resistant (MDR) tubercle bacilli.
AB  - Rifabutin, a spiropiperidyl derivative of rifampicin, is approved for the
      prophylaxis of Mycobacterium avium infections in AIDS patients in the US, and for
      the treatment of M. avium infections, tuberculosis and multiple drug resistant
      tuberculosis in many countries. In the present study, rifabutin was compared with
      rifampicin for its activity against drug susceptible and multi-drug resistant
      tubercle bacilli by several in-vitro and macrophage studies. Rifabutin exhibited
      similar or greater in-vitro activity than rifampicin as judged by the minimal
      inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and
      MBC/MIC ratios, as well as continuous exposure and post-antibiotic effect
      studies. Rifabutin has been shown to be active against some multiple drug
      resistant strains which were resistant to rifampicin. In macrophage studies with
      continuous exposure to the drug or when the drug had been removed after 24 h,
      rifabutin also demonstrated high activity which was better than RMP against
      intracellular tubercle bacilli. This long-acting intracellular anti-mycobacterial
      activity may explain, in part, the clinical efficacy of rifabutin.

PMID- 8522466
TI  - Bactericidal activity and kinetics of RP 59500 in a mouse model of Staphylococcus
      aureus septicaemia.
AB  - The bactericidal activity of RP 59500, a semisynthetic streptogramin, was
      compared with that of vancomycin against Staphylococcus aureus. This activity was
      evaluated in vitro by the kill curve method and in vivo using a model of mouse
      septicaemia. In vitro, RP 59500 (MIC = 0.12 mg/L) was more rapidly bactericidal
      against S. aureus IP 8203 than was vancomycin (MIC = 1 mg/L). In vivo, RP 59500
      (120 mg/kg) was bactericidal against staphylococci in the blood of infected mice
      1 h after administration, an effect which lasted for up to 7 h, whereas
      vancomycin at the same dose was bactericidal only 4 h after administration. The
      serum concentrations of vancomycin were higher than those of RP 59500 for at
      least 4 h after administration, and the Cmax and AUC of vancomycin were 4.8 and
      8.3 times higher, respectively, than those of RP 59500 (Cmax = 13.2 mg/L; AUC0(
      1) = 15.2 mg/L/h), although the agents had similar elimination half-lives (about
      0.5 h). RP 59500 was also administered to mice as a fractionated dose (30 mg/kg x
      4, 40 mg/kg x 3, 60 mg/kg x 2). The onset of its bactericidal effect was delayed
      by fractionating the dose, but the suppression of bacteria in the blood was
      prolonged.

PMID- 8522467
TI  - The effects of amphotericin B, fluconazole and miconazole on neutrophil and
      lymphocyte function in a guinea pig model.
AB  - We studied the effects of amphotericin B, fluconazole and miconazole on guinea
      pig neutrophil and lymphocyte function. Neutrophil adherence, chemotaxis, and
      deoxyglucose uptake and mitogen-induced lymphocyte proliferation were examined.
      The drugs were administered intraperitoneally in varying dosages based on those
      used therapeutically, either as a single infusion or daily for 3 days. Miconazole
      at high dosage (60 mg/kg) suppressed mitogen-induced lymphocyte proliferation,
      otherwise a single dose of any of the drugs had no effect on neutrophil or
      lymphocyte function irrespective of concentration used. Variable stimulative or
      suppressive effects on neutrophil and lymphocyte function were observed after
      three daily doses of each drug, but there was no dose-response pattern and the
      effects were erratic. The data show that, contrary to previous findings in vitro,
      amphotericin B, fluconazole and miconazole were not consistently
      immunosuppressive in vivo in this animal model.

PMID- 8522468
TI  - Pharmacokinetics and safety of trovafloxacin (CP-99,219), a new quinolone
      antibiotic, following administration of single oral doses to healthy male
      volunteers.
AB  - Trovafloxacin (CP-99,219) is a new fluoroquinolone antibacterial agent with a
      broad spectrum of activity against Gram-positive and Gram-negative bacteria. The
      pharmacokinetics and safety of trovafloxacin were characterised in healthy male
      volunteers after administration of single oral doses of 30, 100, 300, 600 and
      1000 mg. trovafloxacin was rapidly absorbed and serum concentrations reached a
      maximum approximately 1 h after dosing. The corresponding mean Cmax values (mean
      +/- SD) were 0.3 +/- 0.0, 1.5 +/- 0.5, 4.4 +/- 1.1, 6.6 +/- 1.4 and 10.1 +/- 0.5
      mg/L. Terminal-phase half-life was independent of dose, with an overall mean of
      9.9 +/- 2.5 h. Generally, Cmax and AUC0-infinity increased linearly with dose.
      Less than 10% of the administered dose was recovered unchanged in urine. Over the
      dosing range, trovafloxacin renal clearance was fairly constant, averaging 0.67
      +/- 0.36 L/h. Trovafloxacin binding to serum proteins was moderate (70%).
      Trovafloxacin was well tolerated at doses of 300 mg or below. There were no
      significant changes in the clinical chemistry or haematology parameters evaluated
      over the entire dosing range.

PMID- 8522469
TI  - Bioavailability of fluconazole administered via a feeding tube in intensive care
      unit patients.
AB  - Fluconazole, a triazole compound with potent activity against many medically
      important fungi, undergoes rapid oral absorption, and has been shown in healthy
      volunteers to exhibit virtually complete bioavailability. The purpose of this
      study is to evaluate the bioavailability of fluconazole administered via a
      feeding tube with concomitant enteral feeds in intensive care unit patients. Once
      prescribed by the attending physician, fluconazole was administered either as an
      intravenous infusion over 1 h or the tablet was crushed and given via a feeding
      tube with concomitant enteral feeds. Once blood samples were obtained (not before
      the fifth dose) of the first regimen, the patient could be switched over to the
      alternate route and blood samples were again obtained after at least five doses.
      All patients had normal gastrointestinal motility, normal renal, and hepatic
      function. Serum concentrations were determined by a validated HPLC method. The
      area under concentration-time curve (AUC) was calculated using the trapezoidal
      rule; bioavailability was determined from the ratio of
      AUC(tube)/AUC(intravenous). The bioavailability for five patients was calculated
      to be 97.2 +/- 9.8%. Fluconazole retained excellent bioavailability when crushed
      and administered via a feeding tube with or without concomitant enteral feeding
      in critically ill patients. This alternative route of administration promotes
      cost savings and decreases the chance for secondary infection from indwelling
      intravenous catheters.

PMID- 8522470
TI  - Evaluation of an antibiotic prescribing protocol for treatment of acute
      exacerbations of chronic obstructive airways disease in a hospital respiratory
      unit.
AB  - A prescribing protocol for infective exacerbations of chronic obstructive airways
      disease (COAD), specifying the use of oral amoxycillin 500 mg tid (or
      erythromycin 500 mg qid if allergic) as first line therapy, and oral
      ciprofloxacin 500 mg bd as second line treatment, was introduced in 1991. Every
      third sequential admission was screened for the year preceding (1990) and the
      year after (1991) the protocol was implemented. Only those patients with a
      discharge diagnosis of infective exacerbation of COAD, but without pneumonia,
      were included in the analysis. The two groups (1990 and 1991) were matched in
      terms of age, sex and pre-treatment given by their General Practitioner (GP), but
      differed with respect to severity score, with 1991 being more severe. The outcome
      measures showed that duration of hospital stay was comparable as was duration of
      treatment. Response to first line therapy was 68% and 67% for 1990 and 1991,
      respectively. Of those who had received antibiotics from their GP, 67% responded
      to first line therapy, while of those who had not received antibiotics from their
      GP 75% responded. Duration of therapy was shorter in first line responders (mean
      and 95% CI: 7.3 (6.3-8.3) days vs 12.7 (10.1-15.3) days). The mean cost per day
      antibiotic treatment was reduced by 54.6% (95% CI 52.3-56.9%) from 3.77 pounds to
      1.71 pounds. In conclusion, the introduction of antibiotic prescribing guidelines
      for treatment of infective exacerbations of COAD showed no detrimental effect on
      outcome measures, but was associated with a significant reduction in the cost of
      antibiotic therapy.

PMID- 8522471
TI  - Assay of vancomycin by fluorescence polarisation immunoassay and EMIT in patients
      with renal failure.
AB  - Serum with vancomycin concentrations between 5 and 15 mg/L from patients on
      dialysis were assayed by fluorescence polarization immunoassay (FPIA) and enzyme
      multiplied immunoassay technique (EMIT). The concentrations as determined by FPIA
      were higher than those using EMIT (mean difference 2.1 mg/L, S.D. 1.5; range -0.8
      6.3) with substantial interpatient variability in the difference between the two
      assays. This suggests that concentrations of active vancomycin are lower than
      indicated by FPIA and thresholds for redosing may need to be adjusted.

PMID- 8522472
TI  - In-vitro development of resistance to beta-lactam antibiotics in Streptococcus
      pneumoniae.
AB  - Selection of resistant mutants was induced in broth by exposing pneumococci to
      serial sub-inhibitory concentrations of various beta-lactam antibiotics.
      Aminopenicillins selected for resistance to themselves and to cephalosporins
      although cephalosporins tended to select for resistance to their own class, with
      the exception of cefixime which seems to select cross-resistant organisms.

PMID- 8522473
TI  - Activity of sparfloxacin on Staphylococcus epidermidis attached to plastic
      catheters.
AB  - The activity of sparfloxacin on Staphylococcus epidermidis biofilms on different
      plastic catheters was evaluated. Sparfloxacin showed high bactericidal activity
      against S. epidermidis biofilms on Vialon and polyvinylchloride catheters. The
      combination of sparfloxacin with amikacin or rifampicin significantly increased
      its activity against bacterial biofilms on polyurethane and Teflon catheters.

PMID- 8522474
TI  - Cross-resistance analysis for clinafloxacin compared with ciprofloxacin,
      fleroxacin, ofloxacin, and sparfloxacin using a predictor panel of ciprofloxacin
      resistant bacteria.
AB  - Clinafloxacin was significantly more active against fluoroquinolone-resistant
      organisms than ciprofloxacin, ofloxacin, sparfloxacin and fleroxacin.
      Clinafloxacin inhibited 65% of isolates at the recommended breakpoint (< or = 1
      mg/L) compared with only 30.0% for ciprofloxacin, 31.7% for ofloxacin, 32% for
      fleroxacin, and 37.7% for sparfloxacin at their recommended breakpoints. No
      strain susceptible to ciprofloxacin was resistant to the other compounds tested.

PMID- 8522475
TI  - Marked variation in pyrimethamine disposition in AIDS patients treated for
      cerebral toxoplasmosis.
AB  - We have characterized the disposition of pyrimethamine in 20 adults with advanced
      AIDS. After the first dose, the area under concentration versus time curves
      (corrected for dose-size) varied 13-fold. This marked variation in drug levels
      was also noted during accumulation towards steady-state: pyrimethamine levels
      were consistently below the suggested lower end of the therapeutic range (750
      mg/L) in three severely ill patients with perturbed consciousness (two of whom
      received the drug by nasogastric tube). Possible mechanisms for these
      observations are discussed. Pyrimethamine levels may be an important determinant
      of the rate of response to treatment by AIDS patients with toxoplasmosis:
      therapeutic drug monitoring may have a role.

PMID- 8522476
TI  - The application of flow cytometry to the estimation of bacterial antibiotic
      susceptibility.

PMID- 8522477
TI  - The application of flow cytometry to the estimation of bacterial antibiotic
      susceptibility.

PMID- 8522478
TI  - BO-2727, meropenem and imipenem disc diffusion susceptibility testing criteria.

PMID- 8522479
TI  - Sputum and serum pharmacokinetics of loracarbef (LY163892) in patients with
      bronchial sepsis.

PMID- 8522480
TI  - Routine measurement of serum vancomycin concentrations.

PMID- 8522481
TI  - Prognosis and staging of cutaneous T-cell lymphoma.
AB  - Staging of cutaneous T-cell lymphoma incorporates both clinical features of the
      disease, including type of skin involvement and adenopathy, along with
      histopathologic information from lymph node and bone marrow biopsies. Prognostic
      significance of bone marrow involvement and gene rearrangement studies on lymph
      node tissue are discussed, and a simplified staging evaluation is outlined.

PMID- 8522482
TI  - Assessing clinical outcomes in cutaneous T-cell lymphoma.
AB  - It is apparent that multiple end points are required to adequately describe the
      response to therapy for CTCL. Investigators may differ as to which end points are
      best suited for their data. In general, multiple end points provide a better
      overall view of response to treatment as compared with a single end point.
      Regardless, measures of response and end points should be clearly defined and the
      methods of calculating end points clearly stated.

PMID- 8522483
TI  - Topical treatment of early cutaneous T-cell lymphoma.
AB  - The two major topical treatment modalities for cutaneous T-cell lymphoma (CTCL)
      are mechlorethamine (nitrogen mustard) and topical carmustine (BCNU). Topical
      mechorethamine hydrochloride has been used since the late 1950s as therapy for
      CTCL. Topical BCNU solution is a highly effective treatment for early stage
      mycosis fungoides. This article describes these two modalities.

PMID- 8522484
TI  - Electron beam treatment for cutaneous T-cell lymphoma.
AB  - Total skin electron radiation has proven efficacy in treating MF. It is a complex
      technique that requires a dedicated radiation team, involving physicists,
      radiotherapists, and radiation oncologists. A center must treat a sufficiently
      high volume of patients to justify the development of TSE, with appropriate
      organization, time, and expense. The radiation team should be an integral part of
      a multidisciplinary clinical group, including medical oncologists,
      dermatologists, pathologists, and nurses. In these contexts, TSE has
      appropriately been developed in a limited number of centers. Cooperation between
      these centers is essential for further refinement of TSE techniques and for
      evolution of the role of TSE in the management of most patients with MF.

PMID- 8522485
TI  - Ultraviolet radiation for treatment of cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) often begins as limited patches and plaques on
      the skin that can be effectively treated with ultraviolet radiation. Many long
      term remissions and cures have been well documented with the use of ultraviolet
      radiation alone for stage I CTCL. The side effects of this treatment are minimal.

PMID- 8522486
TI  - Interferon in the treatment of cutaneous T-cell lymphoma.
AB  - All of the recombinant interferons are active agents for the systemic treatment
      of mycosis fungoides and Sezary syndrome. The response rates are similar to those
      observed with systemic chemotherapy. There is no clear evidence that combining
      interferons with other systemic therapies increases the response rates. The
      combination of interferon with PUVA provides provocative results. The optimal
      role of interferons in the treatment of mycosis fungoides and Sezary's syndrome
      is undefined.

PMID- 8522487
TI  - Chemotherapy for mycosis fungoides and the Sezary syndrome.
AB  - Although conventional cytotoxic chemotherapy agents used alone or in combination
      have demonstrated activity in MF/SS, there are no studies that clearly
      demonstrate improvement in survival of treated patients. Newer compounds worthy
      of further clinical investigation in these patients include temazolamide, an
      alkylating agent with activity in brain neoplasms, the taxanes, and topoisomerase
      inhibitors, including topotecan and CPT-11. In addition, the combination of
      cytotoxic chemotherapies with biologic modalities, such as targeted toxins and
      immunomodulatory agents, has yet to be explored.

PMID- 8522488
TI  - Photopheresis for the treatment of cutaneous T-cell lymphoma.
AB  - Since its introduction in 1987, photopheresis has provided an additional modality
      in the treatment of patients with CTCL; it should probably be considered as the
      first line of treatment for patients with the erythrodermic stage disease. It is
      clear that in the responders, significant improvement in the quality of life can
      be achieved. The toxicity is minimal. As compared with historical control groups,
      patients treated with photopheresis have a prolonged survival. Although the
      precise therapeutic mechanism is yet to be fully elucidated, substantial evidence
      implicates increased immunogenicity of class I associated peptides specific for
      the malignant cells. Additional issues to be resolved include the role of
      adjunctive therapy, cost effectiveness of this treatment modality, and
      applicability to nonerythrodermic stages of CTCL.

PMID- 8522489
TI  - Experimental therapies in the treatment of cutaneous T-cell lymphoma.
AB  - Although meaningful clinical responses have been demonstrated in cutaneous T-cell
      lymphoma using a number of therapeutic modalities, survival benefits have not
      been demonstrated for the majority of patients. Several novel therapies,
      including retinoids, purine analogs, biologic response modifiers, monoclonal
      antibodies, and fusion toxins have demonstrated activity and clinical promise in
      early studies.

PMID- 8522490
TI  - Epidemiology and clinical manifestations of cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) encompasses a constellation of diseases of
      malignant clonal T lymphocytes that present initially in the skin. Within this
      disease spectrum, mycosis fungoides, and the Sezary syndrome are best known.
      Progress in the understanding of the T-cell malignancies now places other
      clinical entities within this disease classification. The authors review the
      epidemiology and clinical manifestations of CTCL.

PMID- 8522491
TI  - Pathology of cutaneous T-cell lymphoma.
AB  - Clinical features as well as histomorphology and cytomorphology are the golden
      standard for the differentiation of the various nosologic entities of cutaneous
      lymphomas, consisting of pre-lymphomas and pseudolymphomas, abortive lymphoma,
      latent lymphoma, definite low grade malignant lymphoma, and high grade malignant
      lymphoma. Histomorphologic and cytomorphologic criteria allow additional
      subtyping of lymphoproliferative T-cell infiltrates of the skin.

PMID- 8522492
TI  - The immunopathogenesis of cutaneous T-cell lymphoma.
AB  - A perplexing array of immune abnormalities have been described in cutaneous T
      cell lymphoma. This article discusses the mechanisms underlying these immune
      abnormalities. The immune processes that have become disordered are examined with
      reference to the steps involved in generating the disease and how these steps can
      be corrected therapeutically.

PMID- 8522493
TI  - What's this about?

PMID- 8522495
TI  - A survivor's personal experience with domestic violence.

PMID- 8522494
TI  - The physician's responsibility and domestic violence.

PMID- 8522496
TI  - A physician's personal experience with domestic violence.

PMID- 8522497
TI  - From one physician to another: the indiscrimination of domestic violence and what
      one physician is doing to help heal the scars.

PMID- 8522498
TI  - You and the law. The Domestic Abuse Act: the physician's role.

PMID- 8522499
TI  - Familial variables and domestic violence.
AB  - We investigated variables predictive of domestic violence from 64 intake forms at
      a battered women's shelter. The batterer, usually the financial provider, used
      drugs/alcohol. Clients' physical abuse as children was correlated with whether
      their siblings were abused, and to emotional and sexual abuse. Clients' parents
      being alcoholic was correlated with spouse abuse between clients' parents and
      with clients' sexual abuse as a child. Findings support theories viewing domestic
      violence as a familial pattern. Domestic violence is, unfortunately, a common
      place occurrence. Statistics compiled by the Arkansas Coalition Against Violence
      to Women and Children indicate that domestic violence is the major cause of
      injuries to women, exceeding automobile accidents, muggings, and rapes combined.
      National statistics (Healthy People 2000, 1990) reveal that "between 2 and 4
      million women are physically battered each year by partners" (p. 61), with some
      21 to 30% of women having been beaten by a partner at least once (Healthy People
      2000, 1990). Moreover, domestic violence occurs at least once in up to half of
      all marriages. In fact, domestic violence is the most frequently experienced type
      of violent crime (Northeast Arkansas Council..., 1994). This violence also
      extends to children. For example, Healthy People 2000 indicated that "In 1986 an
      estimated 1.6 million children nationwide experienced some form of abuse or
      neglect" (p. 61), with physical abuse being the most common type of abuse. From
      battered women seeking assistance, data have been gathered on both victims and
      abusers. Although battered women can come from different backgrounds,
      commonalities exist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522500
TI  - Expanding indications for thrombolytic therapy.

PMID- 8522501
TI  - Control of tuberculosis in Arkansas nursing homes.

PMID- 8522502
TI  - Arkansas HIV/AIDS report. 1983-1995.

PMID- 8522503
TI  - Radiological case of the month. Blastomycosis osteomyelitis with epidural and
      retropharyngeal abscess.

PMID- 8522504
TI  - A system to generate chromosomal mutations in Lactococcus lactis which allows
      fast analysis of targeted genes.
AB  - A system for generating chromosomal insertions in lactococci is described. It is
      based on the conditional replication of lactococcal pWV01-derived Ori+ RepA-
      vector pORI19, containing lacZ alpha and the multiple cloning site of pUC19.
      Chromosomal AluI fragments of Lactococcus lactis were cloned in pORI19 in RepA+
      helper strain Escherichia coli EC101. The frequency of Campbell-type
      recombinants, following introduction of this plasmid bank into L. lactis (RepA-),
      was increased by combining the system with temperature-sensitive pWV01 derivative
      pVE6007. Transformation of L. lactis MG1363 (pVE6007) with the pORI19 bank of
      lactococcal chromosomal fragments at the permissive temperature allowed
      replication of several copies of a recombinant plasmid from the bank within a
      cell because of the provision in trans of RepA-Ts from pVE6007. A temperature
      shift to 37 degrees C resulted in loss of pVE6007 and integration of the pORI19
      derivatives at high frequencies. A bank of lactococcal mutants was made in this
      way and successfully screened for the presence of two mutations: one in the
      monocistronic 1.3-kb peptidoglycan hydrolase gene (acmA) and one in the hitherto
      uncharacterized maltose fermentation pathway. Reintroduction of pVE6007 into the
      Mal- mutant at 30 degrees C resulted in excision of the integrated plasmid and
      restoration of the ability of ferment maltose. The integration plasmid (pMAL) was
      rescued by using the isolated plasmid content of a restored Mal+ colony to
      transform E. coli EC101. Nucleotide sequencing of the 564-bp chromosomal fragment
      in pMAL revealed an internal part of an open reading frame of which the
      translated product showed significant homology with ATP-binding proteins MalK of
      E. coli, Salmonella typhimurium, and Enterobacter aerogenes and MsmK of
      Streptococcus mutans. This combined use of two types of conditional replicating
      pWV01-derived vectors represents a novel, powerful tool for chromosomal gene
      inactivation, targeting, cloning, and sequencing of the labelled gene.

PMID- 8522505
TI  - Molecular cloning and characterization of a chemotactic transducer gene in
      Pseudomonas aeruginosa.
AB  - A Pseudomonas aeruginosa mutant, defective in taxis toward L-serine but
      responsive to peptone, was selected by the swarm plate method after N-methyl-N'
      nitrosoguanidine mutagenesis. The mutant, designated PCT1, was fully motile but
      failed to show chemotactic responses to glycine, L-serine, L-threonine, and L
      valine. PCT1 also showed weaker responses to some other commonly occurring L
      amino acids than did the wild-type strain PAO1. A chemotactic transducer gene,
      denoted pctA (Pseudomonas chemotactic transducer A), was cloned by phenotypic
      complementation of PCT1. Nucleotide sequence analysis showed that the pctA gene
      encodes a putative polypeptide of 629 amino acids with a calculated mass of
      68,042. A hydropathy plot of the predicted polypeptide suggested that PctA may be
      an integral membrane protein with two potential membrane-spanning regions. The C
      terminal domain of PctA showed high homology with the enteric methyl-accepting
      chemotaxis proteins (MCPs). The most significant amino acid sequence similarity
      was found in the region of MCPs referred to as the highly conserved domain. The
      pctA gene was inactivated by insertion of a kanamycin resistance gene cassette
      into the wild-type gene, resulting in the same observed deficiency in taxis
      toward L-amino acids as PCT1. In vivo methyl labeling experiments with L-[methyl
      3H]methionine showed that this knockout mutant lacked an MCP with a molecular
      weight of approximately 68,000.

PMID- 8522506
TI  - Characterization of transposon Tn5469 from the cyanobacterium Fremyella
      diplosiphon.
AB  - A transposon, designated Tn5469, was isolated from mutant strain FdR1 of the
      filamentous cyanobacterium Fremyella diplosiphon following its insertion into the
      rcaC gene. Tn5469 is a 4,904-bp noncomposite transposon with 25-bp near-perfect
      terminal inverted repeats and has three tandemly arranged, slightly overlapping
      potential open reading frames (ORFs) encoding proteins of 104.6 kDa (909
      residues), 42.5 kDa (375 residues), and 31.9 kDa (272 residues). Insertion of
      Tn5469 into the rcaC gene in strain FdR1 generated a duplicate 5-bp target
      sequence. On the basis of amino acid sequence identifies, the largest ORF,
      designated tnpA, is predicted to encode a composite transposase protein. A 230
      residue domain near the amino terminus of the TnpA protein has 15.4% amino acid
      sequence identity with a corresponding domain for the putative transposase
      encoded by Lactococcus lactis insertion sequence S1 (ISS1). In addition, the
      sequence for the carboxyl-terminal 600 residues of the TnpA protein is 20.0%
      identical to that for the TniA transposase encoded by Tn5090 on Klebsiella
      aerogenes plasmid R751. The TnpA and TniA proteins contain the D,D(35)E motif
      characteristic of a recently defined superfamily consisting of bacterial
      transposases and integrase proteins of eukaryotic retroelements and
      retrotransposons. The two remaining ORFs on Tn5469 encode proteins of unknown
      function. Southern blot analysis showed that wild-type F. diplosiphon harbors
      five genomic copies of Tn5469. In comparison, mutant strain FdR1 harbors an extra
      genomic copy of Tn5469 which was localized to the inactivated rcaC gene. Among
      five morphologically distinct cyanobacterial strains examined, none was found to
      contain genomic sequences homologous to Tn5469.

PMID- 8522507
TI  - Repression of 4-hydroxybenzoate transport and degradation by benzoate: a new
      layer of regulatory control in the Pseudomonas putida beta-ketoadipate pathway.
AB  - Pseudomonas putida PRS2000 degrades the aromatic acids benzoate and 4
      hydroxybenzoate via two parallel sequences of reactions that converge at beta
      ketoadipate, a derivative of which is cleaved to form tricarboxylic acid cycle
      intermediates. Structural genes (pca genes) required for the complete degradation
      of 4-hydroxybenzoate via the protocatechuate branch of the beta-ketoadipate
      pathway have been characterized, and a specific transport system for 4
      hydroxybenzoate has recently been described. To better understand how P. putida
      coordinates the processes of 4-hydroxybenzoate transport and metabolism to
      achieve complete degradation, the regulation of pcaK, the 4-hydroxybenzoate
      transport gene, and that of pcaF, a gene required for both benzoate and 4
      hydroxybenzoate degradation, were compared. Primer extension analysis and lacZ
      fusions showed that pcaK and pcaF, which are adjacent on the chromosome, are
      transcribed independently. PcaR, a transcriptional activator of several genes of
      the beta-ketoadipate pathway, is required for expression of both pcaF and pcaK,
      and the pathway intermediate beta-ketoadipate induces both genes. In addition to
      these expected regulatory elements, expression of pcaK, but not pcaF, is
      repressed by benzoate. This previously unrecognized layer of regulatory control
      in the beta-ketoadipate pathway appears to extend to the first two steps of 4
      hydroxybenzoate degradation, since levels of 4-hydroxybenzoate hydroxylase and
      protocatechuate 3,4-dioxygenase activities were also depressed when cells were
      grown on a mixture of 4-hydroxybenzoate and benzoate. The apparent consequence of
      benzoate repression is that cells degrade benzoate in preference to 4
      hydroxybenzoate. These findings indicate that 4-hydroxybenzoate transport is an
      integral feature of the beta-ketoadipate pathway in P. putida and that transport
      plays a role in establishing the preferential degradation of benzoate over 4
      hydroxybenzoate. These results also demonstrate that there is communication
      between the two branches of the beta-ketoadipate pathway.

PMID- 8522508
TI  - In vitro recognition of the replication origin of pLS1 and of plasmids of the
      pLS1 family by the RepB initiator protein.
AB  - Rolling-circle replication of plasmid pLS1 is initiated by the plasmid-encoded
      RepB protein, which has nicking-closing (site-specific DNA strand transferase)
      enzymatic activity. The leading-strand origin of pLS1 contains two regions, (i)
      the RepB-binding site, constituted by three directly repeated sequences (iterons
      or the bind region), and (ii) the sequence where RepB introduces the nick to
      initiate replication (the nic region). A series of plasmids, belonging to the
      pLS1 family, show features similar to those of pLS1 and have DNA sequences
      homologous to the pLS1 nic region. In addition, they all share homologies at the
      level of their Rep proteins. However, the bind regions of these plasmids are, in
      general, not conserved. We tested the substrate specificity of purified RepB of
      pLS1. The RepB protein has a temperature-dependent nicking-closing action on
      supercoiled pLS1, as well as on recombinant plasmid DNAs harboring the pLS1 nic
      region. The DNA strand transferase activity of pLS1-encoded RepB was also assayed
      on two plasmids of the pLS1 family, namely, pE194 and pFX2. DNAs from both
      plasmids were relaxed by RepB, provided they had a proper degree of supercoiling;
      i.e., it was necessary to modulate the supercoiling of pE194 DNA to achieve RepB
      mediated DNA relaxation. Single-stranded oligonucleotides containing the nic
      regions of various plasmids belonging to the pLS1 family, including those of
      pE194 and pFX2, were substrates for RepB. In vitro, the RepB protein does not
      need to bind to the iterons for its nicking-closing activity.

PMID- 8522509
TI  - Picrophilus gen. nov., fam. nov.: a novel aerobic, heterotrophic,
      thermoacidophilic genus and family comprising archaea capable of growth around pH
      0.
AB  - Two species belonging to a novel genus of archaea, designated Picrophilus oshimae
      and Picrophilus torridus, have been isolated from two different solfataric
      locations in northern Japan. One habitat harboring both organisms was a dry,
      extremely acidic soil (pH < 0.5) that was heated by solfataric gases to about 55
      degrees C. In the laboratory both species grew heterotrophically on yeast extract
      and poorly on tryptone under aerobic conditions at temperatures between 45 and 65
      degrees C; they grew optimally at 60 degrees C. The pH optimum was 0.7, but
      growth occurred even around pH 0. Under optimal conditions, the generation time
      was about 6 h, yielding densities of up to 10(10) cells per ml. The cells were
      surrounded by a highly filigreed regular tetragonal S-layer, and the core lipids
      of the membrane were mainly bis-phytanyltetraethers. The 16S rRNA sequences of
      the two species were about 3% different. The complete 16S rRNA sequence of P.
      oshimae was 9.3% different from that of the closest relative, Thermoplasma
      acidophilum. The morphology and physiological properties of the two species
      characterize Picrophilus as a novel genus that is a member of a novel family
      within the order Thermoplasmales.

PMID- 8522510
TI  - Mechanics of bacterial macrofiber initiation.
AB  - The twisting and writhing during growth of single-cell filaments of Bacillus
      subtilis which lead to macrofiber formation was studied in both left- and right
      handed forms of strains FJ7 and RHX. Filament bending, touching, and loop
      formation (folding), followed by winding up into a double-strand fiber, were
      documented. Subsequent folds that produced multistrandedness were also examined.
      The rate of loop rotation during winding up was measured for 26 loops from 16
      clones. In most cases, the first loop formed turned at a lower rate than those
      produced by the following cycles of folding. The sequence of folding topologies
      differed in FJ7 and RHX strains and in left- versus right-handed structures.
      Right-handed FJ7 routinely gave rise to four-stranded helices at the second fold,
      whereas left-handed FJ7 and both left-handed and right-handed forms of RHX made
      structures with predominantly two double-stranded helical regions. Left-handed
      RHX structures frequently produced second folds within the initial loop itself,
      resulting in T- or Y-shaped fibers. Sixteen cases in which the initial touch of a
      filament to itself produced a loop that snapped open before it could wind up into
      a double-strand fiber were found. The snap motions were used to obtain estimates
      of the forces generated by helical growth of single filaments and to investigate
      theoretical models involving the material properties of cell filaments. In
      general, the mechanical behavior of growing single-cell filaments and fibers
      consisting of two-, three-, or four-strand helices was similar to that described
      for larger, mature, multifilament macrofibers. The behavior of multicellular
      macrofibers can be understood, therefore, in terms of individual cell growth.

PMID- 8522511
TI  - Cloning of a novel constitutively expressed pectate lyase gene pelB from Fusarium
      solani f. sp. pisi (Nectria haematococca, mating type VI) and characterization of
      the gene product expressed in Pichia pastoris.
AB  - Since plant-pathogenic fungi must penetrate through pectinaceous layers of the
      host cell wall, pectin-degrading enzymes are thought to be important for
      pathogenesis. Antibodies prepared against a pectin-inducible pectate lyase
      (pectate lyase A [PLA]) produced by a phytopathogenic fungus, Fusarium solani f.
      sp. pisi (Nectria haematococca, mating type VI), was previously found to protect
      the host from infection. The gene (pelA) and its cDNA were cloned and sequenced.
      Here we report the isolation of a new pectate lyase gene, pelB, from a genomic
      library of F. solani f. sp. pisi with the pelA cDNA as the probe. A 2.6-kb DNA
      fragment containing pelB and its flanking regions was sequenced. The coding
      region of pelB was amplified by reverse transcription-mediated PCR, using total
      RNA isolated from F. solani pisi culture grown in the presence of glucose as the
      sole carbon source. The predicted open reading frame of pelB would encode a 25.6
      kDa protein of 244 amino acids which has 65% amino acid sequence identity with
      PLA from F. solani f. sp. pisi but no significant homology with other
      pectinolytic enzymes. The first 16 amino acid residues at the N terminus appeared
      to be a signal peptide. The pelB cDNA was expressed in Pichia pastoris, yielding
      a pectate lyase B (PLB) which was found to be a glycoprotein of 29 kDa. PLB was
      purified to homogeneity by using a two-step procedure involving ammonium sulfate
      precipitation followed by Superdex G75 gel filtration chromatography. Purified
      PLB showed optimal lyase activity at pH 10.0. A rapid drop in the viscosity of
      the substrate and Mono Q anion-exchange chromatography of the products generated
      by the lyase showed that PLB cleaved polygalacturonate chains in an endo fashion.
      Western blotting (immunoblotting) with antibodies raised against PLA showed that
      PLB and PLA are immunologically related to each other. The 5' flanking regions of
      both pelA and pelB were translationally fused to the beta-glucuronidase gene and
      introduced into F. solani f. sp. pisi, and beta-glucuronidase activities of the
      transformants were measured. Expression of the marker gene by the transformants
      showed that pelA expression is induced by pectin and repressed by glucose,
      whereas expression of pelB is constitutive and is not subject to glucose
      repression. Reverse transcription-mediated PCR showed that both pelA and pelB are
      expressed when F. solani f. sp. pisi infects pea epicotyl.

PMID- 8522512
TI  - Identification of two targets of the type III protein secretion system encoded by
      the inv and spa loci of Salmonella typhimurium that have homology to the Shigella
      IpaD and IpaA proteins.
AB  - An important virulence factor of Salmonella spp. is their ability to gain access
      to host cells. A type III secretion system encoded in the inv and spa loci of
      these organisms is essential for this phenotype. We have identified two proteins,
      SipA and SipD, whose secretion from the bacterial cells is dependent on this
      system. The genes encoding these proteins are located at centisome 63 on the S.
      typhimurium chromosome, immediately downstream of the previously identified sipB
      and sipC genes (K. Kaniga, S. Tucker, D. Trollinger, and J. E. Galan, J.
      Bacteriol. 177:3965-3971, 1995). Nucleotide sequence analysis of the genes
      encoding these proteins indicated that SipA and SipD have significant sequence
      similarity to the Shigella IpaA and IpaD proteins. A nonpolar null mutation in
      sipD rendered S. typhimurium severely deficient for entry into cultured
      epithelial cells. In addition, this mutant strain exhibited increased secretion
      of a selected group of proteins whose export is controlled by the inv- and spa
      encoded translocon. In contrast, a nonpolar mutation in sipA did not result in an
      invasion defect or in a significant decreased in virulence in a mouse model of
      infection. In addition, we have found an open reading frame immediately
      downstream of SipA that encodes a predicted protein with significant similarity
      to a family of acyl carrier proteins.

PMID- 8522513
TI  - Effects of a minor isoleucyl tRNA on heterologous protein translation in
      Escherichia coli.
AB  - In Escherichia coli, the isoleucine codon AUA occurs at a frequency of about 0.4%
      and is the fifth rarest codon in E. coli mRNA. Since there is a correlation
      between the frequency of codon usage and the level of its cognate tRNA,
      translational problems might be expected when the mRNA contains high levels of
      AUA codons. When a hemagglutinin from the influenza virus, a 304-amino-acid
      protein with 12 (3.9%) AUA codons and 1 tandem codon, and a mupirocin-resistant
      isoleucyl tRNA synthetase, a 1,024-amino-acid protein, with 33 (3.2%) AUA codons
      and 2 tandem codons, were expressed in E. coli, product accumulation was highly
      variable and dependent to some degree on the growth medium. In rich medium, the
      flu antigen represented about 16% of total cell protein, whereas in minimal
      medium, it was only 2 to 3% of total cell protein. In the presence of the cloned
      ileX, which encodes the cognate tRNA for AUA, however, the antigen was 25 to 30%
      of total cell protein in cells grown in minimal medium. Alternatively, the
      isoleucyl tRNA synthetase did not accumulate to detectable levels in cells grown
      in Luria broth unless the ileX tRNA was coexpressed when it accounted for 7 to 9%
      of total cell protein. These results indicate that the rare isoleucine AUA codon,
      like the rare arginine codons AGG and AGA, can interfere with the efficient
      expression of cloned proteins.

PMID- 8522514
TI  - Localization of the stress protein SP21 in indole-induced spores, fruiting
      bodies, and heat-shocked cells of Stigmatella aurantiaca.
AB  - The localization and distribution of the stress protein SP21 in indole-induced
      vegetative cells, fruiting bodies, and heat shocked cells of Stigmatella
      aurantiaca were determined by immunoelectron microscopy. SP21 was found at the
      cell periphery in heat-shocked cells and either at the cell periphery or within
      the cytoplasm in indole-induced cells, often concentrated in clusters. In
      fruiting-body-derived spores, SP21 was located mainly at the cell wall,
      preferentially at the outer periphery. Furthermore, SP21 antigen was associated
      with cellular remnants within the stalk and within the peripheral horizon next to
      the fruiting body.

PMID- 8522515
TI  - Purification and regulatory properties of MarA protein, a transcriptional
      activator of Escherichia coli multiple antibiotic and superoxide resistance
      promoters.
AB  - Expression of the marA or soxS genes is induced by exposure of Escherichia coli
      to salicylate or superoxides, respectively. This, in turn, enhances the
      expression of a common set of promoters (the mar/soxRS regulons), resulting in
      both multiple antibiotic and superoxide resistance. Since MarA protein is highly
      homologous to SoxS, and since a MalE-SoxS fusion protein has recently been shown
      to activate soxRS regulon transcription, the ability of MarA to activate
      transcription of these genes was tested. MarA was overexpressed as a histidine
      tagged fusion protein, purified, cleaved with thrombin (leaving one N-terminal
      histidine residue), and renatured. Like MalE-SoxS, MarA (i) activated the
      transcription of zwf, fpr, fumC, micF, nfo, and sodA; (ii) required a 21-bp
      "soxbox" sequence to activate zwf transcription; and (iii) was "ambidextrous,"
      i.e., required the C-terminal domain of the alpha subunit of RNA polymerase for
      activation of zwf but not fumC or micF. Thus, the mar and soxRS systems use
      activators with very similar specificities and mechanisms of action to respond to
      different environmental signals.

PMID- 8522516
TI  - Characterization of the celB gene coding for beta-glucosidase from the
      hyperthermophilic archaeon Pyrococcus furiosus and its expression and site
      directed mutation in Escherichia coli.
AB  - The celB gene encoding the cellobiose-hydrolyzing enzyme beta-glucosidase from
      the hyperthermophilic archaeon Pyrococcus furiosus has been identified, cloned,
      and sequenced. The transcription and translation gene was overexpressed in
      Escherichia coli, resulting in high-level (up to 20% of total protein) production
      of beta-glucosidase that could be purified by a two-step purification procedure.
      The beta-glucosidase produced by E. coli had kinetic and stability properties
      similar to those of the beta-glucosidase purified from P. furiosus. The deduced
      amino acid sequence of CelB showed high similarity with those of beta
      glycosidases that belong to glycosyl hydrolase family 1, implicating a conserved
      structure. Replacement of the conserved glutamate 372 in the P. furiosus beta
      glucosidase by an aspartate or a glutamine led to a high reduction in specific
      activity (200- or 1,000-fold, respectively), indicating that this residue is the
      active site nucleophile involved in catalysis above 100 degrees C.

PMID- 8522517
TI  - Chemotactic properties of Escherichia coli mutants having abnormal Ca2+ content.
AB  - The calA, calC, and calD mutants of Escherichia coli are known to be sensitive to
      Ca2+ (R. N. Brey and B. P. Rosen, J. Bacteriol. 139:824-834, 1979). In the
      absence of any added stimuli for chemotaxis, both the calC and the calD mutants
      swam with a tumbly bias. Both the calC and the calD mutants were defective in
      chemotaxis as measured by computer analysis, use of swarm plates, and capillary
      assays. The calA mutant was only slightly defective in motility and only slightly
      impaired in chemotaxis. Chemotactically wild-type cells had an intra-cellular
      free-Ca2+ level of about 105 nM. The intracellular free-Ca2+ levels of the
      mutants, as determined by use of the fluorescent Ca2+ indicator dye fura-2 or
      fluo-3, were about 90, about 1,130, and about 410 nM for calA, calC, and calD,
      respectively. Lowering the intracellular free-Ca2+ levels in wild-type cells and
      in the tumbly cal mutants by use of Ca2+ chelators promoted running (smooth
      swimming). Overexpression of CheZ (which causes dephosphorylation of CheY
      phosphate) in the wild type and in the tumbly cal mutants decreased the level of
      tumbliness (which is caused by CheY-phosphate). The calA mutant was 4- to 10-fold
      more resistant than the wild type to the inhibitory effect of omega-conotoxin on
      chemotaxis. omega-Conotoxin had no effect on Ca2+ extrusion by wild-type E. coli;
      that result suggests that omega-conotoxin affects Ca2+ transport at the point of
      entry instead of exit.

PMID- 8522518
TI  - DNA polymerase I function is required for the utilization of ethanolamine, 1,2
      propanediol, and propionate by Salmonella typhimurium LT2.
AB  - Evidence documenting the requirement for a functional DNA polymerase I when
      Salmonella typhimurium LT2 uses ethanolamine (EA), 1,2-propanediol (1,2-PDL), or
      propionate (PRP) as the sole carbon and energy source is presented. Providing rat
      polymerase beta in trans demonstrated that the growth phenotypes observed were
      due exclusively to the lack of DNA polymerase I functions. The location of the
      mutation (a MudI1734 insertion) that rendered cells unable to grow on EA, 1,2
      PDL, or PRP was determined by DNA sequencing to be within the polA gene. polA
      mutants of this bacterium may be unable to repair the damage caused by reactive
      aldehydes generated during the catabolism of EA, 1,2-PDL, or PRP. Consistent with
      this hypothesis, the inhibitory effects of acetaldehyde and propionaldehyde on
      the growth of this polA mutant were demonstrated. A derivative of the polA mutant
      unable to synthesize glutathione (GSH) was markedly more sensitive to
      acetaldehyde and propionaldehyde than was the polA mutant proficient in GSH
      synthesis. This finding was in agreement with the recently proposed role of GSH
      as a mechanism for quenching reactive aldehydes generated during the catabolism
      of these compounds (M. R. Rondon, R. Kazmierczack, and J. C. Escalante-Semerena,
      J. Bacteriol. 177:5434-5439, 1995).

PMID- 8522519
TI  - Biosynthetic origin of mycobacterial cell wall arabinosyl residues.
AB  - Designing new drugs that inhibit the biosynthesis of the D-arabinan moiety of the
      mycobacterial cell wall arabinogalactan is one important basic approach for
      treatment of mycobacterial diseases. However, the biosynthetic origin of the D
      arabinosyl monosaccharide residues themselves is not known. To obtain information
      on this issue, mycobacteria growing in culture were fed glucose labeled with 14C
      or 3H in specific positions. The resulting radiolabeled cell walls were isolated
      and hydrolyzed, the arabinose and galactose were separated by high-pressure
      liquid chromatography, and the radioactivity in each sugar was determined. [U
      14C]glucose, [6-3H]glucose, [6-14C]glucose, and [1-14C]glucose were all converted
      to cell wall arabinosyl residues with equal retention of radioactivity. The
      positions of the labeled atoms in the arabinose made from [1-14C]glucose and [6
      3H]glucose were shown to be C-1 and H-5, respectively. These results demonstrated
      that the arabinose carbon skeleton is formed via the nonoxidative pentose shunt
      and not via hexose decarboxylation or via triose condensations. Since the pentose
      shunt product, ribulose-5-phosphate, is converted to arabinose-5-phosphate as the
      first step in 3-keto-D-manno-octulosonic acid biosynthesis by gram-negative
      bacteria, such a conversion was then searched for in mycobacteria. However, cell
      free enzymatic analysis using both phosphorous nuclear magnetic resonance
      spectrometry and colorimetric methods failed to detect the conversion. Thus, the
      conversion of the pentose shunt intermediates to the D-arabino stereochemistry is
      not via the expected isomerase but rather must occur via novel metabolic
      transformations.

PMID- 8522520
TI  - Structure and organization of plasmid genes required to produce the translation
      inhibitor microcin C7.
AB  - The translation inhibitor microcin C7 (MccC7) is a linear heptapeptide whose N
      terminus has been replaced by an N-formyl group and whose C terminus has been
      replaced by the phosphodiester of 5'-adenylic acid and n-aminopropanol (J. I.
      Guijarro, J. E. Gonzalez-Pastor, F. Baleux, J. L. San Millan, M. A. Castilla, M.
      Rico, F. Moreno, and M. Delepierre, J. Biol. Chem. 270:23520-23532, 1995). MccC7
      production and immunity determinants lie on a 6.2-kb region of the Escherichia
      coli plasmid pMccC7. This region was entirely sequenced. It contains six open
      reading frames, which were shown to be true genes by different complementary
      approaches. Five genes, mccABCDE, which are transcribed in the same direction,
      are required to produce mature extracellular microcin. The sixth gene, mccF,
      adjacent to mccE, is transcribed in the opposite direction and encodes specific
      self-immunity. Genes mccA to -E constitute an operon transcribed from a promoter
      (mccp) located upstream of mccA. mccA is 21 nucleotides long and encodes the
      unmodified heptapeptide (J. E. Gonzalez-Pastor, J. L. San Millan, and F. Moreno,
      Nature [London] 369:281, 1994). A comparison of predicted gene polypeptide
      products with those included in databases shows that an 81-amino-acid stretch of
      MccB is strikingly homologous to fragments of the same length of proteins ThiF
      and ChlN from E. coli, HesA from Anabaena sp. strain PCC7120, and UBA1, the
      ubiquitin-activating enzyme from different eukaryotic species. MccC displays
      several hydrophobic domains, suggesting a transmembrane location. The carboxyl
      end of MccE displays 41.2% identity with RimL, a protein required to acetylate
      the ribosome protein L12 from E. coli. In the absence of the other mcc genes,
      mccA impairs the growth of host cells, suggesting that unmodified MccA has
      antibiotic activity. A model for MccC7 biosynthesis, export, and immunity is
      proposed.

PMID- 8522521
TI  - Expression and characterization of the Escherichia coli fdo locus and a possible
      physiological role for aerobic formate dehydrogenase.
AB  - In the presence of nitrate, the major anaerobic respiratory pathway includes
      formate dehydrogenase (FDH-N) and nitrate reductase (NAR-A), which catalyze
      formate oxidation coupled to nitrate reduction. Two aerobically expressed
      isoenzymes, FDH-Z and NAR-Z, have been recently characterized. Enzymatic analysis
      of plasmid subclones carrying min 88 of the Escherichia coli chromosome was
      consistent with the location of the fdo locus encoding FDH-Z between the fdhD and
      fdhE genes which are necessary for the formation of both formate dehydrogenases.
      The fdo locus produced three proteins (107, 34, and 22 kDa) with sizes similar to
      those of the subunits of the purified FDH-N. In support to their structural role,
      these polypeptides were recognized by antibodies specific to FDH-N. Expression of
      a chromosomal fdo-uidA operon fusion was induced threefold by aerobic growth and
      about twofold by anaerobic growth in the presence of nitrate. However, it was
      independent of the two global regulatory proteins FNR and ArcA, which control
      genes for anaerobic and aerobic functions, respectively, and of the nitrate
      response regulator protein NARL. In contrast, a mutation affecting either the
      nucleoid-associated H-NS protein or the CRP protein abolished the aerobic
      expression. A possible role for FDH-Z during the transition from aerobic to
      anaerobic conditions was examined. Synthesis of FDH-Z was maximal at the end of
      the aerobic growth and remained stable after a shift to anaerobiosis, whereas FDH
      N production developed only under anaerobiosis. Furthermore, in an fnr strain
      deprived of both FDH-N and NAR-A activities, aerobically expressed FDH-Z and NAR
      Z enzymes were shown to reduce nitrate at the expense of formate under anaerobic
      conditions, suggesting that this pathway would allow the cell to respond quickly
      to anaerobiosis.

PMID- 8522522
TI  - MlpA, a lipoprotein required for normal development of Myxococcus xanthus.
AB  - The mlpA gene encoding a 236-residue polypeptide has been identified immediately
      downstream of the oar gene of Myxococcus xanthus (M. Martinez-Canamero, J. Munoz
      Dorado, E. Farez-Vidal, M. Inouye, and S. Inouye, J. Bacteriol. 175:4756-4763,
      1993). The amino-terminal 21 residues of MlpA encode a typical prokaryotic signal
      sequence with a putative lipoprotein cleavage site. When expressed in Escherichia
      coli in the presence of [2-3H]glycerol, 3H-labeled MlpA had a molecular mass of
      33 kDa and was found to be associated with the membrane fraction. Globomycin, an
      inhibitor of signal peptidase II, caused a shift in the mobility of E. coli
      expressed MlpA to 35 kDa. Subsequently, a mlpA disruption strain (oar+) was
      constructed and found to have delayed fruiting body formation (by approximately
      36 h), with significantly larger fruiting bodies being produced compared with
      those of the wild-type strain. Nevertheless, spore yields for the two strains
      were identical after 120 h of development. These data indicate that MlpA, the
      lipoprotein identified in M. xanthus, is required for normal fruiting body
      formation.

PMID- 8522523
TI  - Synthesis of multiple exoproducts in Pseudomonas aeruginosa is under the control
      of RhlR-RhlI, another set of regulators in strain PAO1 with homology to the
      autoinducer-responsive LuxR-LuxI family.
AB  - Mutants of Pseudomonas aeruginosa PAO1 that were deficient in the ability to
      produce proteases that degrade casein were detected among the survivors of
      chemical mutagenesis. One such mutant (PDO31) showed reduced production of
      elastolytic activity, beta-hemolytic activity, and pyocyanin. A 4.3-kb EcoRI
      fragment from a gene bank of PAO1 that complemented defects in PDO31 was found.
      Transposon mutagenesis and deletion derivatives of the clone were used in
      conjunction with complementation tests to determine the physical location of the
      gene of interest. Nucleotide sequence analysis revealed an open reading frame
      (rhlR) encoding a putative 27.6-kDa protein (RhlR) with homology to autoinducer
      responsive regulators of quorum sensing systems such as LuxR of Vibrio fischeri
      and LasR of P. aeruginosa. Further sequence analysis downstream of rhlR revealed
      an independently transcribed gene (rhlI) that encodes a putative 22.2-kDa protein
      with homology to members of the family of autoinducer synthetases, such as LuxI
      of V. fischeri and LasI of P. aeruginosa. The rhlRI sequences were also recently
      reported by others (U.A. Ochsner and J. Reiser, Proc. Natl. Acad. Sci. USA 92:
      6424-6428, 1995) as an autoinducer-mediated regulation mechanism for rhamnolipid
      biosurfactant synthesis in P. aeruginosa PG201. Mutants with defects in rhlR or
      rhlI were constructed in PAO1 by gene replacement, using clones modified by Tn501
      insertion. Compared with the wild type, the rhlR and rhlI mutants both showed
      defects in the production of elastase, LasA protease, rhamnolipid, and pyocyanin.
      Transcription from the gene for elastase, as measured with a lasB-cat fusion,
      demonstrated that production of elastase was subject to cell density-dependent
      gene activation in PAO1. However, transcription of lasB-cat in the rhlI mutant,
      which had lost the presumptive autoinducer synthetase (predicted to activate
      RhlR), showed low basal activity and had lost all cell density-dependent
      transcription of lasB. Thus, RhlR-RhlI represent the second autoinducer
      responsive regulatory mechanism found in P. aeruginosa that controls expression
      of multiple virulence factor exoproducts, including elastase.

PMID- 8522524
TI  - Phylogenetic analysis of phospholipase C genes from Clostridium perfringens types
      A to E and Clostridium novyi.
AB  - The phylogenetic interrelationships between strains of 5 toxin types (A to E) of
      Clostridium perfringens were examined by analysis of differences in the
      nucleotide sequences of phospholipase C genes (plc genes) among 10 strains,
      including 3 strains for which the plc gene sequences have been previously
      reported. A plc gene was also cloned from a Clostridium novyi type A strain and
      sequenced to analyze the interspecies diversity of plc genes. Phylogenetic trees
      constructed by the neighbor-joining method revealed that the phylogeny of C.
      perfringens strains is not related to toxin typing, in agreement with the results
      of a comparative genome mapping study by Canard et al. (B. Canard, B. Saint
      Joanis, and S. T. Cole, Mol. Microbiol. 6:1421-1429, 1992). Various C.
      perfringens phospholipase C enzymes were purified from cultures of Escherichia
      coli cells into which the encoding plc genes had been cloned. All of the enzymes
      showed the same specific activity. On the other hand, the level of plc
      transcripts differed greatly (up to 40-fold) from one C. perfringens strain to
      another. No significant difference in the nucleotide sequence of the plc promoter
      region was observed for any of the plc genes. These results suggest that the
      variation in phospholipase C activity among different strains is not due to
      mutation in the plc coding region but to that in an extragenic region. The
      evolution of C. perfringens phospholipase C is discussed on the basis of
      similarities and differences between clostridial plc genes.

PMID- 8522525
TI  - A transformation system for the yeast Candida utilis: use of a modified
      endogenous ribosomal protein gene as a drug-resistant marker and ribosomal DNA as
      an integration target for vector DNA.
AB  - We have developed a transformation system for the yeast Candida utilis. A novel
      strategy was applied to construct the transformation system, since auxotrophic
      mutants which could be used as hosts for transformation are not available. A gene
      encoding the ribosomal protein L41 was cloned from C. utilis, which is sensitive
      to cycloheximide, and used as a marker gene conferring cycloheximide resistance
      after modification of its amino acid sequence. The marker gene was constructed by
      substitution of the proline codon at position 56 with the glutamine codon by in
      vitro mutagenesis, as it had been reported previously that the 56th amino acid
      residue of L41 is responsible for the cycloheximide sensitivity of various
      organisms (S. Kawai, S. Murao, M. Mochizuki, I. Shibuya, K. Yano, and M. Takagi,
      J. Bacteriol. 174:254-262 1992). The ribosomal DNA (i.e., DNA coding for rRNA) of
      C. utilis was also cloned and used as a multiple-copy target for the integration
      of vector DNA into the genome, which resulted in a high transformation
      efficiency. Transformants were obtained by electroporation with a maximum
      efficiency of approximately 1,400 transformants per 1 microgram of linearized DNA
      carrying the gene for cycloheximide resistance and part of the ribosomal DNA. No
      transformants were obtained with intact plasmids. Multiple copies of the
      linearized plasmid were integrated into the host chromosome by homologous
      recombination. Southern analysis of the transformants in which vector DNA was
      integrated at the L41 gene locus indicated that there are two copies of gene for
      the L41 protein per cell, suggesting that C. utilis is diploid. Transformants
      were obtained from a variety of C. utilis strains, indicating that this method is
      applicable to the transformation of other C. utilis strains, even though there is
      significant heterogeneity in chromosomal karyotypes among these strains.

PMID- 8522526
TI  - Purification of the copper response extracellular proteins secreted by the copper
      resistant methanogen Methanobacterium bryantii BKYH and cloning, sequencing, and
      transcription of the gene encoding these proteins.
AB  - When the copper-resistant methanogen Methanobacterium bryantii BKYH was exposed
      to 1 mM Cu(II), it secreted approximately fourfold increased levels of three
      proteins, copper response extracellular (CRX) proteins. The members of the CRX
      protein trio had apparent molecular masses of 40.8, 42.3, and 42.9 kDa and were
      purified together from the culture supernatant and separated from each other by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino
      acid sequences of the three proteins were essentially identical, and antibodies
      raised against one of the trio reacted with all three proteins and with three
      other intracellular proteins with slightly higher molecular weights. The N
      terminal amino acid sequence of one of these larger proteins was different from
      that of the secreted CRX proteins. The gene crx, which encodes the CRX proteins,
      was cloned and sequenced, and crx transcription was characterized. The crx
      sequence predicts that the encoded polypeptide is synthesized as a precursor with
      an N-terminal leader peptide, containing 28 amino acid residues, that is removed
      during the extracellular secretion of the CRX proteins. Transcription was
      initiated 274 bp upstream from the crx gene, producing an approximately 1.4-kb
      monocistronic transcript that was present in M. bryantii BKYH cells under all
      growth conditions but that increased approximately fourfold in vivo in response
      to Cu addition. The CRX proteins appear to be glycosylated, since they react with
      concanavalin A and neuraminidase, and to be the products of one gene that have
      different levels of posttranslational glycosylation. This is supported by very
      similar chromatographic and electrophoretic properties, identical N-terminal
      amino acid sequences, immunological cross-reactivities, and the detection of only
      one crx-related sequence by Southern blotting. Western blots (immunoblots) showed
      no evidence for CRX proteins in cell lysates of several other Methanobacterium
      strains.

PMID- 8522527
TI  - Ferrichrome transport in Escherichia coli K-12: altered substrate specificity of
      mutated periplasmic FhuD and interaction of FhuD with the integral membrane
      protein FhuB.
AB  - FhuD is the periplasmic binding protein of the ferric hydroxamate transport
      system of Escherichia coli. FhuD was isolated and purified as a His-tag-labeled
      derivative on a Ni-chelate resin. The dissociation constants for ferric
      hydroxamates were estimated from the concentration-dependent decrease in the
      intrinsic fluorescence intensity of His-tag-FhuD and were found to be 0.4 microM
      for ferric aerobactin, 1.0 microM for ferrichrome, 0.3 microM for ferric
      coprogen, and 5.4 microM for the antibiotic albomycin. Ferrichrome A,
      ferrioxamine B, and ferrioxamine E, which are poorly taken up via the Fhu system,
      displayed dissociation constants of 79, 36, and 42 microM, respectively. These
      are the first estimated dissociation constants reported for a binding protein of
      a microbial iron transport system. Mutants impaired in the interaction of ferric
      hydroxamates with FhuD were isolated. One mutated FhuD, with a W-to-L mutation at
      position 68 [FhuD(W68L)], differed from wild-type FhuD in transport activity in
      that ferric coprogen supported promotion of growth of the mutant on iron-limited
      medium, while ferrichrome was nearly inactive. The dissociation constants of
      ferric hydroxamates were higher for FhuD(W68L) than for wild-type FhuD and lower
      for ferric coprogen (2.2 microM) than for ferrichrome (156 microM). Another
      mutated FhuD, FhuD(A150S, P175L), showed a weak response to ferrichrome and
      albomycin and exhibited dissociation constants two- to threefold higher than that
      of wild-type FhuD. Interaction of FhuD with the cytoplasmic membrane transport
      protein FhuB was studied by determining protection of FhuB degradation by trypsin
      and proteinase K and by cross-linking experiments. His-tag-FhuD and His-tag-FhuD
      loaded with aerobactin specifically prevented degradation of FhuB and were cross
      linked to FhuB. FhuD loaded with substrate and also FhuD free of substrate were
      able to interact with FhuB.

PMID- 8522528
TI  - Role of the ferric uptake regulator of Pseudomonas aeruginosa in the regulation
      of siderophores and exotoxin A expression: purification and activity on iron
      regulated promoters.
AB  - The cloned Pseudomonas aeruginosa fur (ferric uptake regulator) gene was
      overexpressed in P. aeruginosa by using a T7 expression system, and the Fur
      protein (PA-Fur) was purified by using a combination of ion-exchange
      chromatography and metal affinity chromatography. The DNA binding activity of the
      PA-Fur protein was confirmed by gel mobility shift assays and DNase I footprints
      of the synthetic DNA fragment GATAAT GATAATCATTATC, representing a perfect "Fur
      box". In addition, it was shown that PA-Fur is capable of binding to promoter and
      operator determinants of the tightly iron-regulated Escherichia coli fepA-fes
      enterobactin gene system. The activity of PA-Fur on the promoters of iron
      regulated genes involved in the production of two siderophores, pyochelin and
      pyoverdin, and in the expression of exotoxin A was investigated. Data indicating
      that the promoters of the pchR gene, encoding a transcriptional activator for
      pyochelin synthesis, and of the pvdS gene, encoding a positive regulator for
      pyoverdin production, are specifically recognized by Fur-Fe(II) are presented,
      suggesting that PA-Fur represses expression of pchR and pvdS during growth in an
      iron-replete environment. However, neither the promoter region of the gene
      encoding exotoxin A (toxA) nor the promoters of the regAB operon, required for
      toxA expression, interacted with high concentrations of purified PA-Fur. These
      data indicate that iron regulation of exotoxin A production involves additional
      factors which may ultimately be under the control of PA-Fur.

PMID- 8522529
TI  - Superlytic hemolysin mutants of Serratia marcescens.
AB  - Hemolysis by Serratia marcescens is caused by two proteins, ShlA and ShlB. ShlA
      is the hemolysin proper, and ShlB transports ShlA through the outer membrane,
      whereby ShlA is converted into a hemolysin. Superhemolytic ShlA derivatives that
      displayed 7- to 20-fold higher activities than wild-type ShlA were isolated.
      ShlA80 carried the single amino acid replacement of G to D at position 326
      (G326D), ShlA87 carried S386N, and ShlA80III carried G326D and N236D.
      Superhemolysis was attributed to the greater stability of the mutant ShlA
      derivatives because they aggregated less than the wild-type hemolysin, which lost
      activity within 3 min at 20 degrees C. In contrast to the highly hemolytic wild
      type ShlA at 0 degrees C, the hyperlytic hemolysins were nonhemolytic at 0
      degrees C, suggesting that the hyperlytic derivatives differed from wild-type
      ShlA in adsorption to and insertion into the erythrocyte membrane. However, the
      size of the pores formed at 20 degrees C by superhemolytic hemolysins could not
      be distinguished from that of wild-type ShlA. In addition to the N-terminal
      sequence up to residue 238, previously identified to be important for activation
      and secretion, sites 326 and 386 contribute to hemolysin activity since they are
      contained in regions that participate in hemolysin inactivation through
      aggregation.

PMID- 8522530
TI  - Interactive regulation of Azorhizobium nifA transcription via overlapping
      promoters.
AB  - The Azorhizobium nifA promoter (PnifA) is positively regulated by two
      physiological signal transduction pathways, NtrBC, which signals anabolic N
      status, and FixLJK, which signals prevailing O2 status. Yet, PnifA response (gene
      product per unit time) to these two activating signals together is more than
      twice that of the summed, individual signals. In the absence of NIFA, a negative
      PnifA autoregulator, the fully induced PnifA response is more than 10-fold
      greater than that of summed, individual signals. Given this synergism, these two
      signal transduction pathways must interactively regulate PnifA activity. PnifA
      carries three cis-acting elements, an anaerobox, which presumably binds FIXK, a
      NIFAbox, which presumably binds NIFA itself, and a sigma 54 box, which presumably
      binds sigma 54 initiator, a subunit of RNA polymerase. For combinatorial
      analysis, single, double, and triple promoter mutations were constructed in these
      cis-acting elements, and PnifA activities were measured in six different trans
      acting background, i.e., fixK, fixJ, nifA, ntrC, rpoF, and wild type. Under all
      physiological conditions studied, high-level PnifA activity required both FIXK in
      trans and the anaerobox element in cis. Surprisingly, because PnifA was
      hyperactive with a mutated sigma 54box, this cis-acting element mediates both
      negative and positive control. Because PnifA hyperactivity also required a wild
      type upstream NIFAbox element, even in the absence of NIFA, a second upstream
      nifA transcription start superimposed on the NIFAbox element was hypothesized.
      When nifA mRNA 5' start points were mapped by primer extension, both a minor
      upstream transcript(s) starting 45 bp distal to the anaerobox and a major
      downstream transcript starting 10 bp distal to the sigma 54 box were observed. In
      Azorhizobium, RNA polymerase sigma 54 initiator subunits are encoded by a
      multigene family, which includes rpoF and rpoN genes. Because rpoF mutants show
      an Ntr+ phenotype, whereas rpoN mutants are Ntr-, multiple sigma 54 initiators
      are functionally distinct. Two independent rpoF mutants both show a tight Nif-
      phenotype. Moreover, rpoF product sigma 54F is absolutely required for high-level
      PnifA activity. In summary, the Azorhizobium nifA gene carries overlapping
      housekeeping-type and sigma 54-type promoters which interactively respond to
      different signals. Effectively, the upstream, housekeeping-type promoter responds
      to FIXK and positively regulates the downstream, sigma 54-type promoter. The
      downstream, sigma 54-type promoter responds to NTRC and negatively regulates the
      upstream, housekeeping-type promoter. In terms of transcript yield, the upstream,
      housekeeping-type promoter is therefore weak, and the downstream, sigma 54-type
      promoter is strong.

PMID- 8522531
TI  - Identification, cloning, and nucleotide sequence of a silent S-layer protein gene
      of Lactobacillus acidophilus ATCC 4356 which has extensive similarity with the S
      layer protein gene of this species.
AB  - The bacterial S-layer forms a regular structure, composed of a monolayer of one
      (glyco)protein, on the surfaces of many prokaryotic species. S-layers are
      reported to fulfil different functions, such as attachment structures for
      extracellular enzymes and major virulence determinants for pathogenic species.
      Lactobacillus acidophilus ATCC 4356, which originates from the human pharynx,
      possesses such an S-layer. No function has yet been assigned to the S-layer of
      this species. Besides the structural gene (slpA) for the S-layer protein (S
      protein) which constitutes this S-layer, we have identified a silent gene (slpB),
      which is almost identical to slpA in two regions. From the deduced amino acid
      sequence, it appears that the mature SB-protein (44,884 Da) is 53% similar to the
      SA-protein (43,636 Da) in the N-terminal and middle parts of the proteins. The C
      terminal parts of the two proteins are identical except for one amino acid
      residue. The physical properties of the deduced S-proteins are virtually the
      same. Northern (RNA) blot analysis shows that only the slpA gene is expressed in
      wild-type cells, in line with the results from sequencing and primer extension
      analyses, which reveal that only the slpA gene harbors a promoter, which is
      located immediately upstream of the region where the two genes are identical. The
      occurrence of in vivo chromosomal recombination between the two S-protein
      encoding genes will be described elsewhere.

PMID- 8522532
TI  - SecA proteins of Bacillus subtilis and Escherichia coli possess homologous amino
      terminal ATP-binding domains regulating integration into the plasma membrane.
AB  - The Bacillus subtilis secA homolog, div, was cloned and expressed at a variety of
      different levels in wild-type and secA mutant strains of Escherichia coli.
      Analysis of Div function showed that it could not substitute for SecA despite
      being present at a wide range of concentrations at or above the physiological
      level. Location of regions of functional similarity between the two proteins
      using div-secA chimeras revealed that only the amino-terminal ATP-binding domain
      of Div could functionally substitute for the corresponding region of SecA. The
      role of this domain was revealed by subcellular localization experiments that
      demonstrated that in both B. subtilis and E. coli Div had cytoplasmic,
      peripheral, and integral membrane distributions similar to those of its SecA
      homolog and that an intact ATP-binding domain was essential for regulating
      integration of this protein into the plasma membrane. These results suggest
      strongly that the previously observed cycle of membrane binding, insertion, and
      deinsertion of SecA protein (A. Economou and W. Wickner, Cell 78:835-843, 1994)
      is common to these two bacteria, and they demonstrate the importance of the
      conserved ATP-binding domain in promoting this cycle.

PMID- 8522533
TI  - Cloning, sequencing, and growth phase-dependent transcription of the coenzyme
      F420-dependent N5,N10-methylenetetrahydromethanopterin reductase-encoding genes
      from Methanobacterium thermoautotrophicum delta H and Methanopyrus kandleri.
AB  - The mer genes, which encode the coenzyme F420-dependent N5,N10
      methylenetetrahydromethanopterin reductases (CH2 = H4MPT reductases), and their
      flanking regions have been cloned from Methanobacterium thermoautotrophicum delta
      H and Methanopyrus kandleri and sequenced. The mer genes have DNA sequences that
      are 57% identical and encode polypeptides with amino acid sequences that are 57%
      identical and 71% similar, with calculated molecular masses of 33.6 and 37.5 kDa,
      respectively. In M. thermoautotrophicum, mer transcription has been shown to
      initiate 10 bp upstream from the ATG translation initiating codon and to generate
      a monocistronic transcript approximately 1 kb in length. This transcript was
      synthesized at all stages of M. thermoautotrophicum delta H growth in batch
      cultures but was found to increase in abundance from the earliest stages of
      exponential growth, reaching a maximum level at the mid-exponential growth phase.
      For comparison, transcription of the ftr gene from M. thermoautotrophicum delta H
      that encodes the formylmethanofuran:tetrahydromethanopterin formyltransferase (A.
      A. DiMarco, K. A. Sment, J. Konisky, and R. S. Wolfe, J. Biol. Chem. 265:472-476,
      1990) was included in this study. The ftr transcript was found similarly to be
      monocistronic and to be approximately 1 kb in length, but, in contrast to the mer
      transcript, the ftr transcript was present at maximum levels at both the early
      and the mid-exponential growth stages.

PMID- 8522534
TI  - Evidence suggesting cis action by the TnaC leader peptide in regulating
      transcription attenuation in the tryptophanase operon of Escherichia coli.
AB  - Expression of the tryptophanase (tna) operon in Escherichia coli is regulated by
      catabolite repression and transcription attenuation. Elevated levels of
      tryptophan induce transcription antitermination at one or more Rho factor
      dependent termination sites in the leader region of the operon. Induction
      requires translation of a 24-residue coding region, tnaC, located in the 319
      nucleotide transcribed leader region preceding tnaA, the structural gene for
      tryptophanase. In the present paper, we show that two bacterial species that lack
      tryptophanase activity, Enterobacter aerogenes and Salmonella typhimurium, allow
      tryptophanase induction and tna operon regulation when they carry a plasmid
      containing the E. coli tna operon. The role of tnaC in induction was examined by
      introducing mutations in a 24-nucleotide segment of tnaC of E. coli surrounding
      and including the crucial Trp codon 12. Some mutations resulted in a noninducible
      phenotype; these mostly introduced nonconservative amino acid substitutions in
      TnaC. Other mutations had little or no effect; these generally were in third
      positions of codons or introduced conservative amino acid replacements. A
      tryptophan-inserting, UGA-reading glutamine suppressor tRNA was observed to
      restore partial regulation when Trp codon 12 of tnaC was changed to UGA. Stop
      codons introduced downstream of Trp codon 12 in all three reading frames
      established that induction requires translation in the natural tnaC reading
      frame. Our findings suggest that the TnaC leader peptide acts in cis to prevent
      Rho-dependent termination.

PMID- 8522535
TI  - Multicopy suppression by asd gene and osmotic stress-dependent complementation by
      heterologous proA in proA mutants.
AB  - Auxotrophic proA mutants of Escherichia coli were complemented by two different
      classes of Corynebacterium glutamicum genes. One of these was the asd gene. The
      E. coli asd gene also complements the same proA alleles. Complementation of proA
      by the asd+ gene requires a high asd dosage and the proB and the proC gene
      products. The reciprocal complementation pattern (asd by the proA+ gene) was not
      observed. This complementation appears to be due to multicopy suppression by a
      proline biosynthetic gene whose product was expected to play a negligible role in
      this pathway. The other class of complementing clones carries the C. glutamicum
      proA gene. Complementation of E. coli proA mutants by the C. glutamicum proA+
      gene was optimal at high osmolarity.

PMID- 8522536
TI  - Corrected gene assignments of Escherichia coli pro- mutations.
AB  - We have reevaluated the gene assignments of the proline mutant alleles of some
      known Pro- Escherichia coli strains. Of nine proline auxotrophs included in the
      study, five presented phenotypes inconsistent with their previously assigned
      genotypes. We discuss the possible sources and the consequences of these
      assignment errors.

PMID- 8522537
TI  - Characterization of Actinobacillus pleuropneumoniae riboflavin biosynthesis
      genes.
AB  - In this paper, we report the identification, cloning, and complete nucleotide
      sequence of four genes from Actinobacillus pleuropneumoniae that are involved in
      riboflavin biosynthesis. The cloned genes can specify production of large amounts
      of riboflavin in Escherichia coli, can complement several defined genetic
      mutations in riboflavin biosynthesis in E. coli, and are homologous to riboflavin
      biosynthetic genes from E. coli, Haemophilus influenzae, and Bacillus subtilis.
      The genes have been designated A. pleuropneumoniae ribGBAH because of their
      similarity in both sequence and arrangement to the B. subtilis ribGBAH operon.

PMID- 8522538
TI  - Physical map of the Bartonella bacilliformis genome.
AB  - The genome of Bartonella bacilliformis was shown to be a single circular DNA
      molecule of about 1,600 kbp having six NotI, four SfiI, and two CeuI sites. A
      physical map of the DNA was constructed by contour-clamped homogeneous electric
      field pulsed-field gel electrophoresis of DNA restriction fragments. rRNA
      operons, the invasion-associated locus, and a flagellin gene were located on the
      map by hybridization.

PMID- 8522539
TI  - Genetic basis of Neisseria gonorrhoeae lipooligosaccharide antigenic variation.
AB  - Neisseria gonorrhoeae lipooligosaccharide (LOS) undergoes antigenic variation at
      a high rate, and this variation can be monitored by changes in a strain's ability
      to bind LOS-specific monoclonal antibodies. We report here the cloning and
      identification of a gene, lsi-2, that can mediate this variation. The DNA
      sequence of lsi-2 has been determined for N. gonorrhoeae 1291, a strain that
      expresses a high-molecular-mass LOS, and a derivative of this strain, RS132L,
      that produces a truncated LOS. In the parental strain, lsi-2 contains a string of
      12 guanines in the middle of its coding sequence. In cells that had antigenically
      varied to produce a truncated LOS, the number of guanines in lsi-2 was altered.
      Site-specific deletions were constructed to verify that expression of a 3.6-kDa
      LOS is due to alterations in lsi-2.

PMID- 8522540
TI  - Tricistronic operon expression of the genes gcaD (tms), which encodes N
      acetylglucosamine 1-phosphate uridyltransferase, prs, which encodes
      phosphoribosyl diphosphate synthetase, and ctc in vegetative cells of Bacillus
      subtilis.
AB  - The gcaD, prs, and ctc genes were shown to be organized as a tricistronic operon.
      The transcription of the prs gene, measured as phosphoribosyl diphosphate
      synthetase activity, and of the ctc gene, measured as beta-galactosidase activity
      specified by a ctc-lacZ protein fusion, were dependent on the promoter in front
      of the gcaD gene. Analysis of cDNA molecules prepared with gcaD-prs-ctc-specified
      mRNA as the template revealed an RNA transcript that encompassed all three
      cistrons.

PMID- 8522541
TI  - The biomechanics of the human patella during passive knee flexion.
AB  - The fundamental objectives of patello-femoral joint biomechanics include the
      determination of its kinematics and of its dynamics, as a function of given
      control parameters like knee flexion or applied muscle forces. On the one hand,
      patellar tracking provides quantitative information about the joint's stability
      under given loading conditions, whereas patellar force analyses can typically
      indicate pathological stress distributions associated for instance with abnormal
      tracking. The determination of this information becomes especially relevant when
      facing the problem of evaluating surgical procedures in terms of standard (i.e.
      non-pathological) knee functionality. Classical examples of such procedures
      include total knee replacement (TKR) and elevation of the tibial tubercle
      (Maquet's procedure). Following this perspective, the current study was oriented
      toward an accurate and reliable determination of the human patella biomechanics
      during passive knee flexion. To this end, a comprehensive three-dimensional
      computer model, based on the finite element method, was developed for analyzing
      articular biomechanics. Unlike previously published studies on patello-femoral
      biomechanics, this model simultaneously computed the joint's kinematics,
      associated tendinous and ligamentous forces, articular contact pressures and
      stresses occurring in the joint during its motion. The components constituting
      the joint (i.e. bone, cartilage, tendons) were modeled using objective forms of
      non-linear elastic materials laws. A unilateral contact law allowing for large
      slip between the patella and the femur was implemented using an augmented
      Lagrangian formulation. Patellar kinematics computed for two knee specimens were
      close to equivalent experimental ones (average deviations below 0.5 degrees for
      the rotations and below 0.5 mm for the translations) and provided validation of
      the model on a specimen by specimen basis. The ratio between the quadriceps
      pulling force and the patellar tendon force was less than unity throughout the
      considered knee flexion range (30-150 degrees), with a minimum near 90 degrees of
      flexion for both specimens. The contact patterns evolved from the distal part of
      the retropatellar articular surface to the proximal pole during progressive
      flexion. The lateral facet bore more pressure than the medial one, with
      corresponding higher stresses (hydrostatic) in the lateral compartment of the
      patella. The forces acting on the patella were part of the problem unknowns, thus
      leading to more realistic loadings for the stress analysis, which was especially
      important when considering the wide range of variations of the contact pressure
      acting on the patella during knee flexion.

PMID- 8522542
TI  - A case for bone canaliculi as the anatomical site of strain generated potentials.
AB  - We address the question of determining the anatomical site that is the source of
      the experimentally observed strain generated potentials (SGPs) in bone tissue.
      There are two candidates for the anatomical site that is the SGP source, the
      collagen-hydroxyapatite porosity and the larger size lacunar-canalicular
      porosity. In the past it has been argued, on the basis of experimental data and a
      reasonable model, that the site of the SGPs in bone is the collagen
      hydroxyapatite porosity. The theoretically predicted pore radius necessary for
      the SGPs to reside in this porosity is 16 nm, which is somewhat larger than the
      pore radii estimated from gas adsorption data where the preponderance of the
      pores were estimated to be in the range 5-12.5 nm. However, this pore size is
      significantly larger than the 2 nm size of the small tracer, microperoxidase,
      which appears to be excluded from the mineralized matrix. In this work a similar
      model, but one in which the effects of fluid dynamic drag of the cell surface
      matrix in the bone canaliculi are included, is used to show that it is possible
      for the generation of SGPs to be associated with the larger size lacunar
      canalicular porosity when the hydraulic drag and electrokinetic contribution of
      the bone fluid passage through the cell coat (glycocalyx) is considered. The
      consistency of the SGP data with this model is demonstrated. A general boundary
      condition is introduced to allow for current leakage at the bone surface. The
      results suggest that the current leakage is small for the in vitro studies in
      which the strain generated potentials have been measured.

PMID- 8522543
TI  - The mechanical properties of the human heel pad: a paradox resolved.
AB  - In vivo and in vitro mechanical testing of the human heel pad gave apparently
      different properties for this structure: the in vivo stiffness is about six times
      lower, whereas the percentage of energy dissipation is about three times higher
      (up to 95% loss). It was postulated that this divergence must be ascribed to the
      lower leg being involved in in vivo heel pad testing. This hypothesis is
      presently evaluated by applying the two experimental procedures formerly used in
      the in vivo (an instrumented pendulum) and in vitro (an Instron servo-hydraulic
      testing machine) investigations on the same isolated heel pad samples. Instron
      load-deformation cycles mimicking pendulum impacts (i.e. 'first loop-half
      cycles') are first evaluated and then compared to real pendulum impacts. When
      performed properly, the pendulum test procedure reveals the same mechanics for
      isolated heel pads as the Instron does. The load-deformation loops are basically
      identical. Thus similar non-linear stiffnesses (about 900 kN m-1 at body weight)
      and comparable amounts of energy dissipation (46.5-65.5%) are found with both
      types of test, still being largely different from the former in vivo results (150
      kN m-1 and 95%, respectively). Therefore, the present findings support the
      hypothesis that the presence of the entire lower leg in in vivo tests indeed
      influences the outcome of the measurements. It must be concluded that the
      previously published in vivo data, if interpreted for the heel pad alone, implied
      not only an incorrectly low resilience but also a value far too low for
      stiffness.

PMID- 8522544
TI  - An EMG-assisted model of trunk loading during free-dynamic lifting.
AB  - One of the continuing challenges in biomechanics has been to assess loading of
      the spine during dynamic lifting exertions. A model was developed to accurately
      simulate multi-dimensional spinal loads and trunk moments from measured muscle
      coactivity and external forces during free-dynamic lifting exertions. Model
      validity was demonstrated by comparing measured and predicted trunk extension
      moments. Its purpose was to examine realistic representations of lifting
      kinetics, kinematics, and dynamic trunk mechanics that may influence spinal
      loading, and to demonstrate that EMG-assisted modeling techniques can be applied
      to the analysis of free-dynamic exertions. Spinal loads and trunk moments were
      predicted from the muscle force vectors and external loads. Muscle tensile forces
      were determined from the product of normalized EMG data modulated to account for
      contractile dynamics, muscle cross sectional area, and muscle force per unit
      cross-sectional area. Model output was physiologically valid, i.e. average
      predicted muscle force per unit cross-sectional area of 50-65 N cm-2, and
      accurately predicted measured, dynamic, lifting moments, with an average R2 =
      0.81 in the sagittal plane and R2 = 0.76 in the lateral plane. Results indicated
      that compressive and shear loading increased significantly with exertion load,
      lifting velocity, and trunk asymmetry.

PMID- 8522545
TI  - Epicardial surface dynamics in the closed-chest normal canine.
AB  - Past studies of the changing three-dimensional shape of the heart in the closed
      chest during the cardiac cycle have been restricted to the measurement of local
      deformations at a relatively few specific locations, and often have required
      surgical procedures that alter the measurements obtained. In the study reported
      here, high precision displacement and velocity measurements were obtained at the
      epicardial interface using a Compton backscatter imaging technique that does not
      require a surgical intervention or contrast injections. Displacement and velocity
      measurements were obtained at more than 200 locations at the epicardial interface
      at 13 ms intervals throughout the cardiac cycle. Measurements of the changing
      shape of the heart during the cardiac cycle with this technique are precise to
      0.1 mm (S.D.). Displacement and velocity patterns recorded in this study confirm
      and integrate the studies of many others and also add new information. An
      unexpected vigorous inward motion of both the LV (39 mm s-1) and RV (26 mm s-1)
      surfaces during isovolumic relaxation and early rapid refill is demonstrated.
      Velocities during this period equal or exceed those that occur during ejection.
      During ejection, inward LV motion at the base of the heart precedes that at the
      apex by 80-90 ms. Posterior LV displacements and velocities during ejection are 4
      6 times greater than those at the anterior and apex. The Compton backscatter
      imaging technique for obtaining undisturbed measurements of cardiac dynamics in
      the closed chest has potential as a non-invasive clinical tool for serial studies
      of cardiac surface motion abnormalities. The data presented can also be used to
      set surface boundary conditions for biomechanical models of heart deformation.

PMID- 8522546
TI  - Pressure-induced mechanical stress in the carotid artery bifurcation: a possible
      correlation to atherosclerosis.
AB  - A possible correlation between regions of high intramural wall stress and the
      development of atherosclerotic lesions in the carotid artery bifurcation is
      investigated. The bifurcation geometry is determined through in vivo studies, as
      well as the analysis of cadaver specimens. Having compiled accurate geometric
      data, two representative finite element models were created in order to determine
      the areas of localized stress concentrations that occur in the bifurcation. The
      artery is assumed isotropic and is mechanically loaded with an incremental
      pressure of 40 mmHg. A highly localized stress concentration of approximately 9
      to 14 times the proximal circumferential wall stress occurs at the point of
      bifurcation. A lower stress concentration of approximately 3 to 4 times the
      proximal circumferential stress occurs over a large area of the sinus bulb.
      Acknowledging that these two regions of the carotid bifurcation are highly
      susceptible to atherosclerotic lesions, it appears possible that a correlation
      between wall stress and atherosclerosis may exist.

PMID- 8522547
TI  - A theoretical solution for the frictionless rolling contact of cylindrical
      biphasic articular cartilage layers.
AB  - Previous studies have shown that interstitial fluid pressurization plays an
      important role in the load support mechanism of articular cartilage under normal
      step loading. These studies have demonstrated that interstitial fluid
      pressurization decreases with time if the applied load is maintained constant. In
      the present study, a theoretical solution is obtained for another common loading
      of articular cartilage, namely the contact of surfaces in rolling motion. Pure
      rolling of symmetrical frictionless cylindrical cartilage layers is analyzed
      under steady state. The linear biphasic model of Mow et al. [J. Biomech. Engng
      102, 73-84 (1980)] is used to describe the mechanical response of articular
      cartilage. The solution of this contact problem reduces to simultaneously solving
      a set of four integral equations, akin to the dual integral problem of elastic
      contact. It is found that the solution is dependent on four non-dimensional
      parameters: Rh = Vb/HAk, W/2 mu b, R/b, and v, where V is the surface velocity, b
      the cartilage thickness, HA the aggregate modulus, mu the shear modulus, v
      Poisson's ratio, k the permeability, R the radius of cylindrical surfaces, and W
      the applied load per unit cylinder length. For Rh << 1, interstitial fluid
      pressurization is found to be negligible, and all the applied load is supported
      by the solid collagen-proteoglycan phase of the tissue, thus causing significant
      cartilage deformation. As Rh increases to a physiological level (Rh approximately
      10(4)), interstitial fluid pressurization may support more than 90% of the total
      applied load, shielding the solid matrix from high effective stresses and
      reducing matrix strains and deformation. The protective effect of interstitial
      fluid pressurization is observed to increase with increasing joint congruence
      (R/b); similarly, as the applied load (W/2 mu b) is increased, a greater
      proportion of it is supported by the fluid. In degenerative cartilage, Rh may
      drop by one or more orders of magnitude, primarily as a result of increased
      permeability. Thus, the protective stress-shielding effect of interstitial fluid
      pressurization may become less effective in diseased tissue, possibly setting a
      pathway for further tissue degeneration.

PMID- 8522548
TI  - Material and compositional properties of selectively demineralized cortical bone.
AB  - Timed immersion in buffered ethylenediamine-tetraacetic acid (EDTA) was used to
      selectively alter the mineral content at each level in the cortical bone
      structural hierarchy. The effects on the mechanical behavior were investigated
      using a combination of experimental techniques which provide collectively a wide
      range of resolution (5 microns to 3 mm). Optical microscopy and histological
      analysis demonstrated a heterogeneous structure consisting of a mineralized
      tissue core surrounded by a layer of demineralized tissue (collagen) whose
      thickness varied depending on the immersion time. The mechanical behaviors of
      treated samples with (intact) and without (core) the surrounding demineralized
      layer were evaluated using three-point flexure. Overall, the intact specimens
      became significantly less brittle with increased immersion time in buffered-EDTA.
      For the core specimens, there was a systematic decrease in the elastic flexural
      properties (E, sigma e, epsilon e). The site-specific properties of the specimens
      were determined using microhardness testing, scanning acoustic microscopy, and
      wavelength dispersive analysis. The mineralization and site-specific properties
      of the mineralized cores were not significantly affected by buffered-EDTA
      immersion; however, histomorphometric analysis showed a decrease in the
      mineralized volume fraction via widening of the pre-existing vascular channels.
      The experimental hierarchy was effective in discerning site-specific property
      changes and the localized heterogeneities resulting from the buffered-EDTA
      treatment. Based on the results of this study, buffered-EDTA treatment can be
      used to facilitate the determination of material and physical properties of
      intact and demineralized tissues within a single cortical bone sample.

PMID- 8522549
TI  - An inverse dynamics model for the analysis, reconstruction and prediction of
      bipedal walking.
AB  - Walking is a constrained movement which may best be observed during the double
      stance phase when both feet contact the floor. When analyzing a measured movement
      with an inverse dynamics model, a violation of these constraints will always
      occur due to measuring errors and deviations of the segments model from reality,
      leading to inconsistent results. Consistency is obtained by implementing the
      constraints into the model. This makes it possible to combine the inverse
      dynamics model with optimization techniques in order to predict walking patterns
      or to reconstruct non-measured rotations when only a part of the three
      dimensional joint rotations is measured. In this paper the outlines of the
      extended inverse dynamics method are presented, the constraints which define
      walking are defined and the optimization procedure is described. The model is
      applied to analyze a normal walking pattern of which only the hip, knee and ankle
      flexions/extensions are measured. This input movement is reconstructed to a
      kinematically and dynamically consistent three-dimensional movement, and the
      joint forces (including the ground reaction forces) and joint moments of force,
      needed to bring about this movement are estimated.

PMID- 8522550
TI  - Osteonal structure better predicts tensile strength of healing bone than volume
      fraction.
AB  - Refractures and secondary fractures occur after removal of internal fixation
      devices even when the X-rays show well-mineralized bony unions. This indicates
      the unreliability of bone density as the only parameter to estimate the strength
      of healing bone. The aim of this study was to show that the strength of healing
      bone is more influenced by microstructural parameters than by bone density. A
      drill hole defect in the sheep tibia was used to investigate bone healing under
      stable conditions. After 4, 6, 9, 12, 24 and 104-week healing periods, bone
      specimens were taken from the healing zone and tested mechanically as well as
      histo-morphologically. The bone volume fraction in the defect increased at the
      beginning faster than the strength. In the later phase (> 24 weeks) the bone
      remodeling process dominated with little increase in bone volume fraction but an
      increase in strength. The increase in strength was linearly correlated to the
      orientation of the bone lamellae. Orientation of the bone lamellae which cannot
      be well visualized in a clinical X-ray, relates to strength more than density.
      Because only density and not microstructure can be well demonstrated in a
      clinical X-ray, a radiographically 'healed' defect may not reflect structural
      restoration for many years.

PMID- 8522551
TI  - Dynamic optimization analysis for equipment setup problems in endurance cycling.
AB  - The goals of the work reported by this article are two-fold. The first is to
      develop a dynamic optimization framework for analysis of equipment setup problems
      in endurance cycling. The second is to illustrate the application of the approach
      by determining an optimal chainring shape. To achieve these goals, a mathematical
      model of the pedaling motion for given trajectories of the net joint moments and
      the rate of change of the chainring radius was derived, and chainring
      optimization was posed as an optimal control problem. The cost functional
      produced a chainring shape that reduced the cost of endurance cycling at 250 W
      and 90 rpm, apparently by taking advantage of mechanical interactions that arise
      as a natural consequence of the movement. However, the predicted joint moments
      required larger peak values during phases of significantly increased joint
      velocity. Thus, the 'optimal' performance predicted by the cost functional
      appears opposed to expectations based on muscle mechanics and illustrates the
      need for further analysis of endurance cycling with a physiologically based cost
      functional.

PMID- 8522552
TI  - A model of spine, ribcage and pelvic responses to a specific lumbar manipulative
      force in relaxed subjects.
AB  - One class of manipulative techniques commonly used during assessment and
      treatment of spinal disorders involves the patient lying face down while the
      therapist slowly applies a posteroanterior force to a selected vertebra. The aim
      of this investigation was to develop a model which was capable of predicting the
      vertebral displacements resulting from such a manipulative force, applied to the
      lumbar spine. A linear three-dimensional finite element model was generated using
      both previously published and original data to define the geometry and material
      properties. The complete model included the ribcage, thoraco-lumbar spine and
      pelvis with their associated soft tissues. The model simulated the relaxed state
      in a normal subject so the muscle forces were assumed to be negligible.
      Sensitivity analysis suggested that if the model was to be used to simulate the
      behaviour of individual subjects, then the model dimensions and pelvic
      constraints should be matched to the particular subject. The model validity was
      studied by comparing the predicted responses with those that have been observed
      in living human subjects. The model predictions were found to be in good
      agreement with the mean observed human responses, with predicted displacements
      being within one standard deviation of the mean observed values. This agreement
      suggests that the model is useful for predicting the linear region responses to
      slowly applied lumbar posteroanterior forces. The simulations predicted that
      appreciable global vertebral displacements (up to 1.5 mm) and rotations (up to 1
      degree) occurred as far away as the middle and lower thoracic spine during low
      lumbar loading. Intervertebral translations were predicted to be 1 mm or more at
      up to four intervertebral joints away from the point of load
      application.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522553
TI  - On the torsional properties of single osteons.

PMID- 8522554
TI  - The importance of colloid osmotic pressure measurements to prevent oncotic
      overdosage during cardiac surgery.
AB  - OBJECTIVE: Colloidal infusion therapy during cardiac surgery has changed from the
      principal use of human albumin to the preference for synthetic colloids. Despite
      the possible interference of synthetic plasma expanders with the biuret
      determination of total plasma protein (TPP), perioperative infusion therapy is
      frequently directed on the basis of TPP and albumin levels. The hypothesis that
      the level of TPP or albumin does not reflect the plasma colloid osmotic pressure
      (COP) if synthetic plasma expanders are used was studied. MATERIALS AND METHODS:
      In 61 patients undergoing elective cardiac surgery the course of COP and its
      correlation to the TPP and albumin levels were investigated. Natural and
      artificial colloids were used for colloidal infusion therapy. RESULTS: No
      correlation between TPP/albumin levels and COP was found preoperatively and on
      arrival at the ICU, only a weak correlation was observed at 24 hours and 48 hours
      postoperatively. The wide range of the confidential interval indicates that the
      COP cannot be estimated correctly neither from the TPP nor the albumin level. The
      postoperative COP was significantly increased compared to the preoperative levels
      indicating oncotic overdosage. CONCLUSIONS: In order to avoid oncotic
      disturbances, indication for colloidal volume replacement during cardiac surgery
      should be controlled by oncometry if natural and synthetic colloids are
      administered.

PMID- 8522555
TI  - The effects of intraoperative autologous whole blood sequestration on the need
      for transfusion of allogenic blood and blood products in coronary bypass
      operations.
AB  - We investigated the effect of intraoperative autologous blood sequestration
      (IABS), an old blood conservation method, on transfusion requirements for
      homologous packed red blood cells (PRBC), platelets, and fresh frozen plasma
      (FFP) for patients undergoing coronary bypass surgery. This non-randomized
      retrospective study involved 204 patients who underwent isolated primary coronary
      artery bypass grafting (CABG). In 140 patients (IABS Group), autologous
      heparinized whole blood was removed intraoperatively via aortic cannula before
      bypass and retransfused at the conclusion of extracorporeal circulation. In 64
      control patients, no IABS was performed. Demographic characteristics and
      operative and perioperative variables for both groups were similar (p > 0.05). In
      140 patients, the mean sequestered blood volume was 1430 ml (range = 700-2100
      ml). The banked PRBC requirement during hospitalization was 1.91 units in the No
      IABS Group and 2.25 units for the IABS Group (p = 0.2957). The need for platelet
      transfusion was 3.06 units in the No IABS Group and 1.09 units in the IABS Group
      (p = 0.0003). In the No IABS Group, 1.31 units of FFP was transfused and in the
      IABS Group, 0.49 units was transfused (p = 0.0004). To identify possible
      confounding factors, we performed a multivariate Poisson regression analysis for
      the 22 patient variables by a forward stepwise procedure. Regression analysis
      indicated that IABS did not alter the need for PRBC transfusion (p = 0.6194) but
      adjusted differences did confirm that IABS was associated with decreased need for
      transfusion of platelets and FFP (p = 0.0001 and p = 0.0002,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522557
TI  - Morphometric features of ruptured congenital sinus of Valsalva aneurysm:
      implication for surgical treatment.
AB  - Five hearts with ruptured congenital sinus of Valsalva aneurysm were studied. In
      3 hearts of Caucasian patients, the sinus of Valsalva aneurysms were located in
      the immediate vicinity of the commissure between the noncoronary and right aortic
      cusps with rupture from the noncoronary sinus to the right atrium (n = 2) and
      from the right sinus to the right ventricle (n = 1). In 2 hearts of indigenous
      North Americans, the defects were sited in the immediate vicinity of the
      commissure between right and left aortic cusps with rupture into the right
      ventricle; both patients had an associated conal septal hypoplasia ventricular
      septal defect and aortic insufficiency. The diameters of the rupture holes at the
      base of the sinus of Valsalva aneurysms in the five hearts ranged from 0.4 to 1.1
      cm (mean 0.7 cm). Histologic examination of longitudinal sections through the
      ruptured sinus of Valsalva showed 0.8 to 1.7 cm (mean 1.1 cm) wide areas in which
      there was lack of continuity between the aortic media and the aortic annulus.
      Conclusions. This study shows that the site of congenital weakness in sinus of
      Valsalva aneurysm in indigenous North American patients may be similar to that in
      Oriental patients, whereas the site tends to be different in Occidental patients.
      It also emphasizes the importance of patch closure rather than suture closure of
      ruptured sinus of Valsalva aneurysms.

PMID- 8522556
TI  - Initial clinical experience with rectus sheath grafts in congenital heart
      defects.
AB  - This study reports on the initial clinical experience using anterior rectus
      sheath as potentially growing graft material in congenital heart lesions. The
      first seven patients with complex congenital lesions requiring a rectus sheath
      graft because of inadequate available pericardium are reviewed. The initial
      operations were: TOF (unicusp pulmonary valve) (re-op), two Konno procedures (one
      VSD and one RV patch), two arterial switch procedures for TGA (neoaortic
      augmentation), two Fontan (re-op) atrial augmentation patch and pulmonary
      arterioplasty (re-op). Ages ranged from 1 week to 15 years. Follow-up ranged from
      1 to 72 months and included open visual inspection at reoperation in 5 cases,
      angiography in 3 cases, and echocardiography in 4 cases. One early respiratory
      death occurred in the fourth postoperative week. So far no early bleeding from
      rectus sheath patches, infection, aneurysmal dilatation, or scar contraction was
      observed. No manifestation of peripheral emboli was seen. Hernias of the harvest
      site were absent. We concluded that in absence of pericardium and in areas where
      future cicatrization or aneurysmal dilatation is undesirable, anterior rectus
      sheath appears to be a reasonable alternative.

PMID- 8522558
TI  - A 8-year follow-up of the Edwards-Duromedics bileaflet prosthesis.
AB  - Following reports of leaflet escapes, distribution of the Edwards-Duromedics
      prosthesis (ED), introduced in 1982, was suspended from 1988 to 1990. From our
      experience of 257 patients operated on between March, 1983, and April, 1988, it
      appeared to us that, among the five key factors identified by extensive studies,
      surgical mishandling, specially in mitral position, could have been the main
      contributing factor. These 257 patients, mean age 57 years (range 2 to 75 years),
      underwent 138 aortic (AVR), 86 mitral (MVR), and 33 double valve (DVR)
      replacements. Hospital mortality was 2.3% (6 patients): 1.4% for AVR, 3.5% for
      MVR, and 3% for DVR, none of them being directly valve-related. But there were 3
      early replacements of a mitral ED for intra or postoperative impingement of one
      leaflet. Follow-up has been 93%, with a total of 1.155 patient-years. Among the
      20 late deaths (8%), 4 (20%) were considered as valve-related; there was one MV
      thrombosis and 7 non-fatal systemic emboli, the total incidence of
      thromboembolism being 0.7% patient-year. No structural failure or leaflet escape
      was observed in this series. At 8 years, actuarial survival, hospital mortality
      excluded, was 85.5% for AVR, 95% for MVR, and 89% for DVR. The ED prosthesis is,
      from a hydrodynamic point of view, an advance in terms of both mechanical and
      bileaflet valve: the valve design accounts for its low thrombogenicity. But its
      persistent drawback remains the prohibitive vertical exposure of leaflets in
      mitral position, that can be responsible for immediate or delayed leaflet
      entrapment, or for incautious handling for rotating the mechanism, leading to
      extensive fissuration of pyrolitic carbon and delayed rupture. (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8522559
TI  - Intermittent aortic regurgitation following aortic valve replacement.
AB  - Intermittent aortic regurgitation is an unusual complication following a
      mechanical prosthesis replacement in the early postoperative period. Arterial
      pressure recording and echocardiographic assessment were enough to diagnose the
      prosthetic dysfunction. Reexploration of the valve confirmed the dysfunction,
      which was caused by a pannus of previous aortic valve replacement with the
      pulmonary valve. The pannus impeded normal closure of the leaflet in an
      intermittent way during diastole. Reorientation of the valve corrected the aortic
      insufficiency. Doppler ultrasound was a very useful noninvasive technique in
      order to evaluate the suspected prosthetic valve dysfunction in the immediate
      postoperative period.

PMID- 8522560
TI  - Open heart surgery in presence of hereditary spherocytosis.
AB  - A patient with ostium secundum atrial septal defect was operated upon despite
      having hereditary spherocytosis, without any hemolytic effects of cardiopulmonary
      bypass. A short bypass time is safe in presence of this congenital hemolytic
      anemia.

PMID- 8522561
TI  - Monitoring of two hearts in one chest.
AB  - A 32 year old patient with end-stage cardiomyopathy underwent heterotopic heart
      transplantation with a small donor heart. Monitoring of this unusual clinical
      setting of two hearts beating independently in one chest required special
      technique and scrutinous interpretation so one can differentiate donor heart from
      recipient heart immediately.

PMID- 8522562
TI  - Resection of hepatoblastoma with right atrial extension using cardiopulmonary
      bypass.
AB  - A 3-year-old boy underwent a successful combined resection of a hepatoblastoma
      and its intracaval right atrial extension using a cardiopulmonary bypass. This
      type of extension is extremely rare in hepatoblastoma. The cardiopulmonary bypass
      enabled complete resection of the intracardiac mass of the hepatoblastoma. In
      addition, dissection and ligation of the right hepatic vein under cardiopulmonary
      bypass made the following right hepatectomy easy and safe.

PMID- 8522563
TI  - Coarctation of the aorta in infants and neonates: results and assessment of
      prognostic variables.
AB  - From 1984 until 1994, 75 consecutive patients younger than 12 months of age were
      operated on for coarctation of the aorta. We retrospectively analyzed predictive
      factors for morbidity and mortality, and also interaction between surgical
      procedures and recoarctation. Surgical procedures were as follows: resection with
      a traditional end-to-end (E-E) anastomosis in 55 patients (73.3%), prosthetic
      patch aortoplasty (PPA) in 12 patients (16%) and subclavian flap aortoplasty
      (SFA) in 8 patients (10.7%). Early mortality was 9.33% (7 patients). Logistic
      regression analysis proved that age at operation, associated anomalies of heart,
      type of coarctation, aortic arch hypoplasia and pulmonary banding were
      independent predictors of hospital death. Late mortality occurred in 7 patients
      (10.3%). Associated anomalies of heart were an independent prognostic factor for
      late mortality. Actuarial freedom from recoarctation at 1 year was 91%
      [confidence limits (CL): 82% to 97%] and 5 years were 74% (CL: 67% to 86%).
      Immediate postrepair gradient was equal after E-E anastomosis and other
      procedures. We conclude that the treatment of first choice in the management of
      coarctation of the aorta in infants is E-E anastomosis.

PMID- 8522564
TI  - Optimal site for proximal and distal anastomoses in AAAs repair.
AB  - The replacement of straight graft for vascular aortic reconstruction, in the
      elective treatment of aortic and aorto-iliac aneurysms, is advisable and requires
      only two anastomoses and a low surgical risk. In our report we have tried to
      identify the simplest vascular reconstruction for juxtarenal involvement (15% in
      our experience), reducing the surgical time and the operative (or postoperative)
      injuries. The decision to employ the tube or the bifurcated reconstruction
      depends on the surgeon's assessment of the degree of common iliac dilatation, the
      presence of an iliac aneurysm or the concomitance of occlusive disease of the
      iliac-femoral district. Some authors extend the bifurcated repair to prevent the
      possible future occlusive events or iliac dilatation. We have much information
      about the natural history of aortic aneurysms but we have also to define the
      indications for a valuable surgical reconstruction. We have considered a
      consecutive series of 20 patients who underwent elective aortic and aorto-iliac
      aneurysm repair in S. Rita private hospital; in 13 patients (65%) the aneurysms
      were treated with tube grafts, the other patients received bifurcate grafts: 3
      (15%) aorto-bisiliac, 2 (10%) aorto-bifemoral and 2 (10%) right aorto-iliac and
      left aortofemoral bypass procedure. We employed Crawford's inclusion in the
      juxtarenal involvements, generally without the reimplantation of renal arteries,
      extending the tube repair in the aorto-iliac dilatation, obtaining a
      simplification of the surgical procedures. The use of straight graft allows a
      sensible decrease of surgical operating time, a reduction of hematic loss and a
      very low incidence of postoperative injuries; this solution became possible also
      in some selected forms of aneurysmatic involvement of renal arteries.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8522565
TI  - Prevalence and predictive value of ECG findings in acute extremity ischemia.
AB  - OBJECTIVE: To determine the prevalence and predictive value of ECG findings in
      patients treated surgically for acute extremity ischemia. EXPERIMENTAL DESIGN:
      Retrospective study with follow-up for one month. SETTING: Tampere University
      Hospital, Jyvaskyla Central Hospital. PATIENTS: 114 patients with acute extremity
      ischemia treated surgically. INTERVENTIONS: Emergency thromboembolectomy was
      performed to all patients. MEASURES: ECGs, taken preoperatively at the emergency
      department, were analysed according to the Minnesota code. Death was regarded as
      the endpoint of the study. RESULTS: ST-J depression (60.5%) and T-wave inversion
      (71.9%) were the most common single findings. The ECG was considered suggestive
      of ischemic heart disease in 64.0% of patients. The prevalence of atrial
      fibrillation was 37.7%. Atrial fibrillation was found in 25.0% of patients with
      acute thrombotic occlusion and in 43.6% of patients with embolic occlusion (chi 2
      = 3.6, df = 1, p = 0.057). The ECG was suggestive of ischemic heart disease in
      87.5% of patients who died within a month compared to 60.2% in those still alive
      (chi 2 = 4.4, df = 1, p = 0.034). In logistic regression analysis atrial
      fibrillation was found to increase the risk of mortality (B = 0.93, df = 1, p =
      0.002); odds ratio 2.6 (95% CI 1.4-4.7). CONCLUSION: Most patients with acute
      extremity ischemia had significant ECG findings with low prevalence of AF
      reflecting increased ratio of thrombotic occlusions. AF and ECG suggestive of
      ischemic heart disease were also associated to poor short-term prognosis. We
      think that acute thrombosis should be suspected in most patients with acute
      extremity ischemia.

PMID- 8522566
TI  - Phenomenon of concentrical spiral separation of microparticles in laminar
      vortical blood flow.
AB  - 1. Previously unknown phenomenon of a stable ordered laminar vortical blood flow
      of opposite direction has been discovered in the systemic and pulmonary
      circulations consisting in the fact that in the circulation system there exists a
      rotative, twisted, spiral-like blood movement due to (a) special organization of
      intracavitary architectonics of heart and blood vessels in the form of funnel
      like cavities with tangential inflow into the heart, outflow from the heart and
      blood vessel branching, (b) twisting character of contraction of spiral-oriented
      muscular elements creating the ejection effect of the vortical blood jet. 2.
      Previously unknown phenomenon of concentrical spiral separation of blood
      microparticles has been discovered consisting in the fact that in moving blood
      there exists a layered distribution of microparticles on flow radius according to
      their size and mass due tot the stable ordered laminar vortical blood flow of
      opposite direction in the systemic and pulmonary circulations, the largest and
      heaviest microparticles constituting the axial nucleus of the flow and the
      smallest and lightest microparticles constituting parietal layers.

PMID- 8522567
TI  - Hemostatic disorders associated with arterial hypertension and peripheral
      arterial disease.
AB  - To study a possible hypercoagulability in vascular disease, in 22 patients with
      essential hypertension and in 13 patients with obliterative arteriopathies of the
      lower limbs we measured the levels of plasma thrombomodulin (TM), plasma and
      urine beta-thromboglobulin (beta-TG), plasma D-dimer (DD) and plasminogen
      activator-inhibitor (PAI-1) and compared to the values obtained from 10 healthy
      volunteers. The values observed in hypertensive patients show only PAI-1 levels
      significantly higher. All the parameters were found to be significantly increased
      in vasculopathic patients. These data confirm that in vasculopathic patients
      endothelium damage, platelet activation, impaired fibrinolytic potential and
      increase of fibrin turnover, occur. On the other hand, in the hypertensive
      patients, at first stages of the disease, we have found only an increase of PAI-1
      plasma levels documenting impaired fibrinolytic potential.

PMID- 8522568
TI  - Incisional hernias: incidence following abdominal aortic aneurysm repair.
AB  - It is thought there is an increased incidence of incisional herniation after the
      repair of an abdominal aortic aneurysm. We sought to assess this premise by
      reviewing 281 patients who had undergone abdominal aortic aneurysm repair over
      the preceding eight years at Concord Hospital. Incisional hernias were found in
      fourteen patients. This made up 5% of the total group having surgery (281
      patients) or 6% of those surviving 12 months or more after operation (231
      patients). Of these 231 patients, seven had transverse incision hernias (6.7% of
      all those with transverse incisions), and seven had vertical incision hernias
      (5.4% of all those with vertical incisions). Six of the fourteen patients with a
      hernia had needed an urgent repair of an abdominal aortic aneurysm. We conclude
      from this study, that there is no evidence of an increased incidence of
      incisional hernias associated with aneurysmal disease itself. Rather, the factors
      causing such hernias are common to all laparotomies for major disease in sick,
      elderly patients, in the absence of intra-abdominal sepsis.

PMID- 8522569
TI  - A long term follow-up of one of the first arterial homografts.
AB  - OBJECTIVE: To report a successful long term homograft of an artery. EXPERIMENTAL
      DESIGN: Surgical arterial homograft with a long term follow up. SETTING: General
      surgery wards of two general hospitals. PATIENTS: 2 patients, one with a
      recurrent sarcoma of the thigh, the other with an osteogenic sarcoma of the
      humerus. INTERVENTION: Surgical removal of all tissue of the groin including
      femoral and external iliac artery and vein, femoral nerve, lymphatics, muscle and
      ligaments. Arterial replacement with homograft from second patient. RESULTS:
      Successful function of arterial homograft for 40 years. CONCLUSIONS: It is
      possible that arteries could be added to the list of organs that are harvested
      for transplantation.

PMID- 8522570
TI  - True aneurysm of the inferior thyroid artery. Case report and review of the
      literature.
AB  - In a patient already operated for abdominal aortic aneurysm fifteen months
      previously, because of the onset of aspecific vertigo, instrumental
      investigations of the supra aortic vessels showed us the presence of a non
      palpable mass, in the left side of the neck. Duplex Scanner, angio-CT and
      Angiography let us suspect the presence of an aneurysm located somewhere in the
      course of the thyrocervical trunk. At the operation the aneurysm, which we
      originally suspected to be a false and a possibly iatrogenic one, in the reality
      was a true aneurysm and was located at the termination of the thyrocervical
      trunk, just in the first segment of the inferior thyroid artery. The case is
      reported because of its rarity and the difficulties in the preoperative
      diagnosis.

PMID- 8522571
TI  - A new autogenous conduit for the spleno-renal shunt.
AB  - Management of patients with portal hypertension has been significantly advanced
      by new medical, surgical and radiologic procedures. In the presence of portal
      vein thrombosis, a splenorenal shunt is the procedure of choice for relief of
      portal hypertension. The gonadal vein is an autogenous conduit of ideal diameter
      to accomplish this objective. Several advantages of this new operation are
      described.

PMID- 8522572
TI  - CYFRA 21-1 determination in patients with non-small cell lung cancer: clinical
      utility for the detection of recurrences.
AB  - The aim of this study was to evaluate serial determinations of CYFRA 21-1 in the
      follow-up of patients treated surgically for non-small cell lung cancer in order
      to predict the risk of tumour recurrence. Serum levels of CYFRA 21-1 were
      measured using an immunoradiometric assay (CIS bio) in 57 patients with operable
      non-small cell lung cancer (NSCLC): 25 with squamous cell carcinoma (SqCC), 20
      with adenocarcinoma (AC), 12 with large cell carcinoma (LCC) and 30 with non
      malignant lung diseases. Elevated preoperative CYFRA 21-1 levels were identified
      in 44% of all patients with NSCLC. The diagnostic specificity of the assay was
      97%. Positive CYFRA 21-1 levels was observed in 30% of stage I, 33% of stage II,
      and 55% of stage IIIa. Statistically significant differences were obtained
      between stages I and IIIa, II and IIIa, but not between stages I and II. During
      follow-up recurrence was observed in 19 of 57 (33%) NSCLC patients. Recurrence
      free survival probability for patients with elevated serum CYFRA 21-1 levels
      before surgery was 52% (13/25), versus 81% (26/32) for patients with normal serum
      CYFRA 21-1 levels (p < 0.01). In 15 patients with increased trend for CYFRA 21-1,
      elevated serum CYFRA 21-1 levels preceded (13 patients) or coincided (2 patients)
      with the clinical detection of tumour recurrence, providing a predictive value of
      an increased trend of 87%. In the multivariate analysis the association of the
      increase of CYFRA 21-1 level with a higher risk of recurrence is statistically
      significant (p < 0.001).

PMID- 8522573
TI  - Pain management in video assisted thoracic surgery: evaluation of localised
      partial rib resection. A new technique.
AB  - We undertook a re-evaluation of acute and chronic pain generation following Video
      Assisted Thoracic Surgery (VATS) with regard to chest wall trauma produced by the
      instruments and their ports. From intercostal space (ICS) measurements made on 40
      patients, it was confirmed that both the camera and the staple gun port diameters
      are too large for insertion without trauma. An instrument was produced (the
      "Sari" Punch, Bolton Surgical Services, Sheffield, England) which cleanly excises
      an elipse of the superior aspect of a rib, prior to the introduction of the
      ports. At the same time, the recommended orbit of the instruments about the
      surgical focus was abandoned in favour of an alignment along one ICS so that only
      one nerve was potentially traumatised. These modifications were then combined
      with balanced, pre-emptive and continuous paravertebral analgesia and the
      efficacy of this approach was evaluated in nine patients undergoing VATS.
      Operation of the rib punch was easy in all patients and was carried out without
      clinical or radiological trauma to the rib. Insertion of the ports was easy and
      access was good to all intrathoracic structures. Postoperative analgesia was good
      and the mean hospital stay was 2.7 days (range 2-4). Follow-up two months later
      confirmed a satisfactory surgical procedure and no patients complained of chest
      wall pain or numbness. We conclude that pain generation with VATS must be
      seriously considered if the technique is to become truly successful. Balanced,
      pre-emptive, paravertebral analgesia will protect the central nervous system
      while the removal of an elipse of rib and alignment of the instruments along one
      ICS will reduce the likelihood of peripheral nerve trauma.

PMID- 8522574
TI  - Bronchial carcinoid associated with Cushing's syndrome.
AB  - Bronchial carcinoid is the most frequent cause of Cushing's syndrome due to
      ectopic ACTH production. The authors report a case of bronchial carcinoid which
      diagnosis was difficult because of the presence of pulmonary mycosis, that
      determined a hypercorticosuprarenalism. Medical treatment with octreotide,
      ketoconazolo and mitotane was useless, and bilateral suprarenalectomy was
      performed. A scintigraphy with raced somatostatin revealed a left lung area
      capting radiation. A CT scan of the thorax revealed a lesion of the lingula and
      the patient underwent an atypical lung resection with complete solution of the
      symptom. The problems of diagnosis and treatment of neuroendocrine tumors of the
      lung are discussed and the importance of SSA in the diagnostic procedure is
      pointed out.

PMID- 8522575
TI  - Delayed postpneumonectomy empyema.
AB  - OBJECTIVE: Most postpneumonectomy empyemas occur shortly after the surgery, but
      rarely do they manifest much later. We present our experience in treating two
      cases of delayed postpneumonectomy empyema and discuss its clinical features.
      EXPERIMENTAL DESIGN: The diagnosis of delayed empyema is difficult as patients
      present with nonspecific symptoms. Consequently, there was a delay of several
      weeks in reaching the correct diagnosis. This is a retrospective case study of
      two patients. SETTING: The patients were admitted to hospital for appropriate
      care. PATIENTS: Two patients were diagnosed as having delayed postpneumonectomy
      empyema from consequential infection. Chest X-ray may provide helpful information
      such as the presence of air-fluid level or a mediastinal shift toward the
      remaining lung (by accumulation of pus in the postpneumonectomy cavity).
      INTERVENTION: The patients were treated surgically. RESULTS: In both cases the
      diagnosis of postpneumonectomy empyema was delayed, but eventually correct
      diagnosis was made. The outcome of the surgical therapy was successful.
      CONCLUSIONS: Delayed postpneumonectomy empyema is a rare condition. The etiology
      in the majority of cases is probably due to hematogenous spread of bacteria from
      other parts of the body. Correct diagnosis of this condition is often delayed.
      The treatment is surgical.

PMID- 8522576
TI  - An infrequent complication of Swan-Ganz catheters.
AB  - The Swan-Ganz catheter complications are infrequent, the most typical one being
      cardiac arrhythmias. The breaking and embolization of a catheter fragment into
      the pulmonary vascular system are exceptional and, in any case, benign. We
      present a patient with severe pulmonary hypertension to the embolization of a
      Swan-Ganz catheter fragment into the right pulmonary artery which disappeared
      with the movements of the fragment to the lung periphery.

PMID- 8522577
TI  - Chromosomes initiate spindle assembly upon experimental dissolution of the
      nuclear envelope in grasshopper spermatocytes.
AB  - Chromosomes are known to enhance spindle microtubule assembly in grasshopper
      spermatocytes, which suggested to us that chromosomes might play an essential
      role in the initiation of spindle formation. Chromosomes might, for example,
      activate other spindle components such as centrosomes and tubulin subunits upon
      the breakdown of the nuclear envelope. We tested this possibility in living
      grasshopper spermatocytes. We ruptured the nuclear envelope during prophase,
      which prematurely exposed the centrosomes to chromosomes and nuclear sap. Spindle
      assembly was promptly initiated. In contrast, assembly of the spindle was
      completely inhibited if the nucleus was mechanically removed from a late prophase
      cell. Other experiments showed that the trigger for spindle assembly is
      associated with the chromosomes; other constituents of the nucleus cannot
      initiate spindle assembly in the absence of the chromosomes. The initiation of
      spindle assembly required centrosomes as well as chromosomes. Extracting
      centrosomes from late prophase cells completely inhibited spindle assembly after
      dissolution of the nuclear envelope. We conclude that the normal formation of a
      bipolar spindle in grasshopper spermatocytes is regulated by chromosomes. A
      possible explanation is an activator, perhaps a chromosomal protein (Yeo, J.-P.,
      F. Alderuccio, and B.-H. Toh. 1994a. Nature (Lond.). 367: 288-291), that promotes
      and stabilizes the assembly of astral microtubules and thus promotes assembly of
      the spindle.

PMID- 8522578
TI  - Two novel related yeast nucleoporins Nup170p and Nup157p: complementation with
      the vertebrate homologue Nup155p and functional interactions with the yeast
      nuclear pore-membrane protein Pom152p.
AB  - We have taken a combined genetic and biochemical approach to identify major
      constituents of the yeast nuclear pore complex (NPC). A synthetic lethal screen
      was used to identify proteins which interact genetically with the major pore
      membrane protein Pom152p. In parallel, polypeptides present in similar amounts to
      Pom152p in a highly enriched preparation of yeast NPCs have been characterized by
      direct microsequencing. These approaches have led to the identification of two
      novel and major nucleoporins, Nup170p and Nup157p. Both Nup170p and Nup157p are
      similar to each other and to an abundant mammalian nucleoporin, Nup155p (Radu,
      A., G. Blobel, and R. W. Wozniak. 1993. J. Cell Biol. 121: 1-9) and
      interestingly, nup170 mutants can be complemented with mammalian NUP155. In
      addition, the synthetic lethal screen identified genetic interactions between
      Pom152p and two other major nucleoporins, Nup188p (Nehrbass, U., S. Maguire, M.
      Rout, G. Blobel, and R. W. Wozniak, manuscript submitted for publication), and
      Nic96p (Grandi, P., V. Doye, and E. C. Hurt. 1993. EMBO J. 12: 3061-71). We have
      determined that together, Nup170p, Nup157p, Pom152p, Nup188p, and Nic96p comprise
      greater than one-fifth of the mass of the isolated yeast NPC. Examination of the
      genetic interactions between these proteins indicate that while deletion of
      either POM152, NUP170, or NUP188 alone is not lethal, pairwise combinations are.
      Deletion of NUP157 is also not lethal. However, nup157 null mutants, while lethal
      in combination with nup170 and nup188 null alleles, are not synthetically lethal
      with pom152 null alleles. We suggest that Nup170p and Nup157p may be part of a
      morphologically symmetrical but functionally distinct substructure of the yeast
      NPC, e.g., the nucleoplasmic and cytoplasmic rings. Finally, we observed
      morphological abnormalities in the nuclear envelope as a function of alterations
      in the expression levels of NUP170 suggesting a specific stoichiometric
      relationship between NPC components is required for the maintenance of normal
      nuclear structure.

PMID- 8522579
TI  - Thiol agents and Bcl-2 identify an alphavirus-induced apoptotic pathway that
      requires activation of the transcription factor NF-kappa B.
AB  - Oxidative stress has been proposed as a common mediator of apoptotic death. To
      investigate further the role of oxidants in this process we have studied the
      effects of antioxidants on Sindbis virus (SV)-induced apoptosis in two cell
      lines, AT-3 (a prostate carcinoma line) and N18 (a neuroblastoma line). The thiol
      antioxidant, N-acetylcysteine (NAC), at concentrations above 30 mM, completely
      abrogates SV-induced apoptosis in AT-3 and N18 cells. The effects of NAC cannot
      be attributed to inhibition of viral entry or viral replication, changes in
      extracellular osmolarity or to increases in cellular glutathione levels, nor can
      they be mimicked by chelators of trace metals, inhibitors of lipid peroxidation
      or peroxide scavengers. In contrast, other thiol agents including pyrrolidine
      dithiocarbamate (PDTC, 75 microM) are protective. Because NAC and PDTC are among
      the most effective inhibitors of the transcription factor NF-kappa B, we examined
      SV's ability to activate NF-kappa B before the onset of morphologic or
      biochemical evidence of apoptosis. Within hours of infection, SV induced a robust
      increase in nuclear NF-kappa B activity in AT-3 and N18 cells; this activation
      was suppressible by NAC and PDTC. Over-expression of bcl-2 in AT-3 cells, which
      has been shown to inhibit SV-induced apoptosis, also inhibits SV-induced NF-kappa
      B activation. To determine if NF-kappa B activation is necessary for SV-induced
      apoptosis in these cells, we used double stranded oligonucleotides with consensus
      NF-kappa B sequences as transcription factor decoys (TFDs) to inhibit NF-kappa B
      binding to native DNA sites. Wild-type, but not mutant, TFDs inhibit SV-induced
      apoptosis in AT-3 cells. In contrast, TFD inhibition of NF-kappa B nuclear
      activity in N18 cells did not prevent SV-induced apoptosis. Taken together, these
      observations define a cell type-specific, transcription factor signaling pathway
      necessary for SV-induced apoptosis. Understanding the precise mechanism by which
      Bcl-2 and thiol agents inhibit SV-induced nuclear NF-kappa B activity in AT-3
      cells may provide insights into the pluripotent antiapoptotic actions of these
      agents.

PMID- 8522580
TI  - Interaction between BiP and Sec63p is required for the completion of protein
      translocation into the ER of Saccharomyces cerevisiae.
AB  - To clarify the roles of Kar2p (BiP) and Sec63p in translocation across the ER
      membrane in Saccharomyces cerevisiae, we have utilized mutant alleles of the
      essential genes that encode these proteins: kar2-203 and sec63-1. Sanders et al.
      (Sanders, S. L., K. M. Whitfield, J. P. Vogel, M. D. Rose, and R. W. Schekman.
      1992. Cell. 69:353-365) showed that the translocation defect of the kar2-203
      mutant lies in the inability of the precursor protein to complete its transit
      across the membrane, suggesting that the lumenal hsp70 homologue Kar2p (BiP)
      binds the transiting polypeptide in order to facilitate its passage through the
      pore. We now show that mutation of a conserved residue (A181-->T) (Nelson, M. K.,
      T. Kurihara, and P. Silver. 1993. Genetics. 134:159-173) in the lumenal DnaJ box
      of Sec63p (sec63-1) results in an in vitro phenotype that mimics the precursor
      stalling defect of kar2-203. We demonstrate by several criteria that this
      phenotype results specifically from a defect in the lumenal interaction between
      Sec63p and BiP: Neither a sec62-1 mutant nor a mutation in the cytosolically
      exposed domain of Sec63p causes precursor stalling, and interaction of the sec63
      1 mutant with the membranebound components of the translocation apparatus is
      unimpaired. Additionally, dominant KAR2 suppressors of sec63-1 partially relieve
      the stalling defect. Thus, proper interaction between BiP and Sec63p is necessary
      to allow the precursor polypeptide to complete its transit across the membrane.

PMID- 8522581
TI  - Transferrin-binding protein complex is the receptor for transferrin uptake in
      Trypanosoma brucei.
AB  - In Trypanosoma brucei, the products of two genes, ESAG 6 and ESAG 7, located
      upstream of the variant surface glycoprotein gene in a polycistronic expression
      site form a glycosylphosphatidylinositol-anchored transferrin-binding protein
      (TFBP) complex. It is shown by gel filtration and membrane-binding experiments
      that the TFBP complex is heterodimeric and binds one molecule of transferrin with
      high affinity (2,300 binding sites per cell; KD = 2.1 nM for the dominant
      expression site from T. brucei strain 427 and KD = 131 nM for ES1.3A of the EATRO
      1125 stock). The ternary transferrin-TFBP complexes with iron-loaded or iron-free
      ligand are stable between pH 5 and 8. Cellular transferrin uptake can be
      inhibited by 90% with Fab fragments from anti-TFBP antibodies. After uptake, the
      TFBP complex and its ligand are routed to lysosomes where transferrin is
      proteolytically degraded. While the degradation products are released from the
      cells, iron remains cell associated and the TFBP complex is probably recycled to
      the membrane of the flagellar pocket, the only site for exo- and endocytosis in
      this organism. It is concluded that the TFBP complex serves as the receptor for
      the uptake of transferrin in T. brucei by a mechanism distinct from that in
      mammalian cells.

PMID- 8522582
TI  - Direct membrane retrieval into large vesicles after exocytosis in sea urchin
      eggs.
AB  - At fertilization in sea urchin eggs, elevated cytosolic Ca2+ leads to the
      exocytosis of 15,000-18,000 1.3-microns-diam cortical secretory granules to form
      the fertilization envelope. Cortical granule exocytosis more than doubles the
      surface area of the egg. It is thought that much of the added membrane is
      retrieved by subsequent endocytosis. We have investigated how this is achieved by
      activating eggs in the presence of aqueous- and lipid-phase fluorescent dyes. We
      find rapid endocytosis of membrane into 1.5-microns-diam vesicles starting
      immediately after cortical granule exocytosis and persisting over the following
      15 min. The magnitude of this membrane retrieval can compensate for the changes
      in the plasma membrane of the egg caused by exocytosis. This membrane retrieval
      is not stimulated by PMA treatment which activates the endocytosis of clathrin
      coated vesicles. When eggs are treated with short wave-length ultraviolet light,
      cortical granule exocytosis still occurs, but granule cores fail to disperse.
      After egg activation, large vesicles containing semi-intact cortical granule
      protein cores are observed. These data together with experiments using sequential
      pulses of fluid-phase markers support the hypothesis that the bulk of membrane
      retrieval immediately after cortical granule exocytosis is achieved through
      direct retrieval into large endocytotic structures.

PMID- 8522583
TI  - Gap junction turnover, intracellular trafficking, and phosphorylation of
      connexin43 in brefeldin A-treated rat mammary tumor cells.
AB  - Intercellular gap junction channels are thought to form when oligomers of
      connexins from one cell (connexons) register and pair with connexons from a
      neighboring cell en route to forming tightly packed arrays (plaques). In the
      current study we used the rat mammary BICR-M1Rk tumor cell line to examine the
      trafficking, maturation, and kinetics of connexin43 (Cx43). Cx43 was conclusively
      shown to reside in the Golgi apparatus in addition to sites of cell-cell
      apposition in these cells and in normal rat kidney cells. Brefeldin A (BFA)
      blocked Cx43 trafficking to the surface of the mammary cells and also prevented
      phosphorylation of the 42-kD form of Cx43 to 44- and 46-kD species. However,
      phosphorylation of Cx43 occurred in the presence of BFA while it was still a
      resident of the ER or Golgi apparatus yielding a 43-kD form of Cx43. Moreover,
      the 42- and 43-kD forms of Cx43 trapped in the ER/Golgi compartment were
      available for gap junction assembly upon the removal of BFA. Mammary cells
      treated with BFA for 6 h lost preexisting gap junction "plaques," as well as the
      44- and 46-kD forms of Cx43 and functional coupling. These events were reversible
      1 h after the removal of BFA and not dependent on protein synthesis. In summary,
      we provide strong evidence that in BICR-M1Rk tumor cells: (a) Cx43 is transiently
      phosphorylated in the ER/Golgi apparatus, (b) Cx43 trapped in the ER/Golgi
      compartment is not subject to rapid degradation and is available for the assembly
      of new gap junction channels upon the removal of BFA, (c) the rapid turnover of
      gap junction plaques is correlated with the loss of the 44- and 46-kD forms of
      Cx43.

PMID- 8522584
TI  - Dictyostelium myosin I double mutants exhibit conditional defects in pinocytosis.
AB  - The functional relationship between three Dictyostelium myosin Is, myoA, myoB,
      and myoC, has been examined through the creation of double mutants. Two double
      mutants, myoA-/B- and myoB-/C-, exhibit similar conditional defects in fluid
      phase pinocytosis. Double mutants grown in suspension culture are significantly
      impaired in their ability to take in nutrients from the medium, whereas they are
      almost indistinguishable from wild-type and single mutant strains when grown on a
      surface. The double mutants are also found to internalize gp126, a 116-kD
      membrane protein, at a slower rate than either the wild-type or single mutant
      cells. Ultrastructural analysis reveals that both double mutants possess numerous
      small vesicles, in contrast to the wild-type or myosin I single mutants that
      exhibit several large, clear vacuoles. The alterations in fluid and membrane
      internalization in the suspension-grown double mutants, coupled with the altered
      vesicular profile, suggest that these cells may be compromised during the early
      stages of pinocytosis, a process that has been proposed to occur via actin-based
      cytoskeletal rearrangements. Scanning electron microscopy and rhodamine
      phalloidin staining indicates that the myosin I double mutants appear to extend a
      larger number of actin-filled structures, such as filopodia and crowns, than wild
      type cells. Rhodamine-phalloidin staining of the F-actin cytoskeleton of these
      suspension-grown cells also reveals that the double mutant cells are delayed in
      the rearrangement of cortical actin-rich structures upon adhesion to a substrate.
      We propose that myoA, myoB, and myoC play roles in controlling F-actin filled
      membrane projections that are required for pinosome internalization in
      suspension.

PMID- 8522585
TI  - Essential role of caldesmon in the actin filament reorganization induced by
      glucocorticoids.
AB  - Glucocorticoids induce the remodeling of the actin cytoskeleton and the formation
      of numerous stress fibers in a protein synthesis-dependent fashion in a variety
      of cell types (Castellino, F., J. Heuser, S. Marchetti, B. Bruno, and A. Luini.
      1992. Proc. Natl. Acad. Sci. USA. 89:3775-3779). These cells can thus be used as
      models to investigate the mechanisms controlling the organization of actin
      filaments. Caldesmon is an almost ubiquitous actin- and calmodulin-binding
      protein that synergizes with tropomyosin to stabilize microfilaments in vitro
      (Matsumura, F., and Yamashiro, S. 1993. Current Opin. Cell Biol. 5:70-76). We now
      report that glucocorticoids (but not other steroids) enhanced the levels of
      caldesmon (both protein and mRNA) and induced the reorganization of
      microfilaments with similar time courses and potencies in A549 cells. A caldesmon
      antisense oligodeoxynucleotide targeted to the most abundant caldesmon isoform in
      A549 cells dramatically inhibited glucocorticoid-induced caldesmon synthesis and
      actin reorganization with similar potencies. Several control oligonucleotides
      were inactive. These results demonstrate that caldesmon has a crucial role in
      vivo in the organization of the actin cytoskeleton and suggest that hormone
      induced changes in caldesmon levels mediate microfilament remodeling.

PMID- 8522586
TI  - Ezrin oligomers are major cytoskeletal components of placental microvilli: a
      proposal for their involvement in cortical morphogenesis.
AB  - Ezrin is a component of the microvillus cytoskeleton of a variety of polarized
      epithelial cells and is believed to function as a membrane-cytoskeletal linker.
      In this study, we isolated microvilli from human placental syncytiotrophoblast as
      a model system for biochemical analysis of ezrin function. In contrast to
      intestinal microvilli, ezrin is a major protein component of placental
      microvilli, comprising approximately 5% of the total protein mass and present at
      about one quarter of the molar abundance of actin. Gel filtration and chemical
      cross-linking studies demonstrated that ezrin exists mainly in the form of
      noncovalent dimers and higher order oligomers in extracts of placental
      microvilli. A novel form of ezrin, apparently representing covalently cross
      linked adducts, was present as a relatively minor constituent of placental
      microvilli. Both oligomers and adducts remained associated with the detergent
      insoluble cytoskeleton, indicating a tight interaction with actin filaments.
      Moreover, stimulation of human A431 carcinoma cells with EGF induces the rapid
      formation of ezrin oligomers in vivo, thus identifying a signal transduction
      pathway involving ezrin oligomerization coincident with microvillus assembly. In
      addition to time course studies, experiments with tyrosine kinase and tyrosine
      phosphatase inhibitors revealed a correlation between the phosphorylation of
      ezrin on tyrosine and the onset of oligomer formation, consistent with the
      possibility that phosphorylation of ezrin might be required for the generation of
      stable oligomers. Based on these observations, a model for the assembly of cell
      surface structures is proposed.

PMID- 8522588
TI  - The cell cycle-dependent localization of the CP190 centrosomal protein is
      determined by the coordinate action of two separable domains.
AB  - CP190, a protein of 1,096 amino acids from Drosophila melanogaster, oscillates in
      a cell cycle-specific manner between the nucleus during interphase, and the
      centrosome during mitosis. To characterize the regions of CP190 responsible for
      its dynamic behavior, we injected rhodamine-labeled fusion proteins spanning most
      of CP190 into early Drosophila embryos, where their localizations were
      characterized using time-lapse fluorescence confocal microscopy. A single
      bipartite 19-amino acid nuclear localization signal was detected that causes
      nuclear localization. Robust centrosomal localization is conferred by a separate
      region of 124 amino acids; two adjacent, nonoverlapping fusion proteins
      containing distinct portions of this region show weaker centrosomal localization.
      Fusion proteins that contain both nuclear and centrosomal localization sequences
      oscillate between the nucleus and the centrosome in a manner identical to native
      CP190. Fusion proteins containing only the centrosome localization sequence are
      found at centrosomes throughout the cell cycle, suggesting that CP190 is actively
      recruited away from the centrosome by its movement into the nucleus during
      interphase. Both native and bacterially expressed CP190 cosediment with
      microtubules in vitro. Tests with fusion proteins show that the domain
      responsible for microtubule binding overlaps the domain required for centrosomal
      localization. CP60, a protein identified by its association with CP190, also
      localizes to centrosomes and to nuclei in a cell cycle-dependent manner.
      Experiments in which colchicine is used to depolymerize microtubules in the early
      Drosophila embryo demonstrate that both CP190 and CP60 are able to attain and
      maintain their centrosomal localization in the absence of microtubules.

PMID- 8522587
TI  - Mutations in twinstar, a Drosophila gene encoding a cofilin/ADF homologue, result
      in defects in centrosome migration and cytokinesis.
AB  - We describe the phenotypic and molecular characterization of twinstar (tsr), an
      essential gene in Drosophila melanogaster. Two P-element induced alleles of tsr
      (tsr1 and tsr2) result in late larval or pupal lethality. Cytological examination
      of actively dividing tissues in these mutants reveals defects in cytokinesis in
      both mitotic (larval neuroblast) and meiotic (larval testis) cells. In addition,
      mutant spermatocytes show defects in aster migration and separation during
      prophase/prometaphase of both meiotic divisions. We have cloned the gene affected
      by these mutations and shown that it codes for a 17-kD protein in the cofilin/ADF
      family of small actin severing proteins. A cDNA for this gene has previously been
      described by Edwards et al. (1994). Northern analysis shows that the tsr gene is
      expressed throughout development, and that the tsr1 and tsr2 alleles are
      hypomorphs that accumulate decreased levels of tsr mRNA. These findings prompted
      us to examine actin behavior during male meiosis to visualize the effects of
      decreased twinstar protein activity on actin dynamics in vivo. Strikingly, both
      mutants exhibit abnormal accumulations of F-actin. Large actin aggregates are
      seen in association with centrosomes in mature primary spermatocytes. Later,
      during ana/telophase of both meiotic divisions, aberrantly large and misshaped
      structures appear at the site of contractile ring formation and fail to
      disassemble at the end of telophase, in contrast with wild-type. We discuss these
      results in terms of possible roles of the actin-based cytoskeleton in centrosome
      movement and in cytokinesis.

PMID- 8522589
TI  - Stable, detyrosinated microtubules function to localize vimentin intermediate
      filaments in fibroblasts.
AB  - Separate populations of microtubules (MTs) distinguishable by their level of
      posttranslationally modified tubulin subunits and by their stability in vivo have
      been described. In polarized 3T3 cells at the edge of an in vitro wound, we have
      found a striking preferential coalignment of vimentin intermediate filaments
      (IFs) with detyrosinated MTs (Glu MTs) rather than with the bulk of the MTs,
      which were tyrosinated MTs (Tyr MTs). Vimentin IFs were not stabilizing the Glu
      MTs since collapse of the IF network to a perinuclear location, induced by
      microinjection of monoclonal anti-IF antibody, had no noticeable effect on the
      array of Glu MTs. To test whether Glu MTs may affect the organization of IFs we
      regrew MTs in cells that had been treated with nocodazole to depolymerize all the
      MTs and to collapse IFs; the reextension of IFs into the lamella lagged behind
      the rapid regrowth of Tyr MTs, but was correlated with the slower reformation of
      Glu MTs. Similar realignment of IFs with newly formed Glu MTs was observed in
      serum-starved cells treated with either serum or taxol to induce the formation of
      Glu MTs. Next, we microinjected affinity purified antibodies specific for Glu
      tubulin (polyclonal SG and monoclonal 4B8) and specific for Tyr tubulin
      (polyclonal W2 and monoclonal YL1/2) into 3T3 cells. Both injected SG and 4B8
      antibodies labeled the subset of endogenous Glu MTs; W2 and YL1/2 antibodies
      labeled virtually all of the cytoplasmic MTs. Injection of SG or 4B8 resulted in
      the collapse of IFs to a perinuclear region. This collapse was comparable to that
      observed after complete MT depolymerization by nocodazole. Injection of W2,
      YL1/2, or nonspecific control IgGs did not result in collapse of the IFs. Taken
      together, these results show that Glu MTs localize IFs in migrating 3T3
      fibroblasts and suggest that detyrosination of tubulin acts as a signal for the
      recruitment of vimentin IFs to MTs.

PMID- 8522590
TI  - Dynamics of human keratin 18 phosphorylation: polarized distribution of
      phosphorylated keratins in simple epithelial tissues.
AB  - Phosphorylation of keratin polypeptides 8 and 18 (K8/18) and other intermediate
      filament proteins results in their reorganization in vitro and in vivo. In order
      to study functional aspects of human K18 phosphorylation, we generated and
      purified a polyclonal antibody (termed 3055) that specifically recognizes a major
      phosphorylation site (ser52) of human K18 but not dephosphorylated K18 or a ser52
      ->ala K18 mutant. Pulse-chase experiments followed by immunoprecipitation and
      peptide mapping of in vivo 32PO4-labeled K8/18 indicated that the overall
      phosphorylation turnover rate is faster for K18 versus K8, and that ser52 of K18
      is a highly dynamic phosphorylation site. Isoelectric focusing of 32PO4 labeled
      K18 followed by immunoblotting with 3055 showed that the major phosphorylated K18
      species contain ser52 phosphorylation but that some K18 molecules exist that are
      preferentially phosphorylated on K18 sites other than ser52. Immunoblotting of
      total cell lysates obtained from cells at different stages of the cell cycle
      showed that ser52 phosphorylation increases three to fourfold during the S and
      G2/M phases of the cell cycle. Immunofluorescence staining of cells at different
      stages of mitosis, using 3055 or other antibodies that recognize the total
      keratin pool, resulted in preferential binding of the 3055 antibody to the
      reorganized keratin fraction. Staining of human tissues or tissues from
      transgenic mice that express human K18 showed that the phospho-ser52 K18 species
      are located preferentially in the basolateral and apical domains in the liver and
      pancreas, respectively, but no preferential localization was noted in other
      simple epithelial organs examined. Our results support a model whereby
      phosphorylated intermediate filaments are localized in specific cellular domains
      depending on the tissue type and site(s) of phosphorylation. In addition, ser52
      of human K18 is a highly dynamic phosphorylation site that undergoes modulation
      during the S and G2/M phases of the cell cycle in association with filament
      reorganization.

PMID- 8522591
TI  - Chronic hepatitis, hepatocyte fragility, and increased soluble
      phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved
      arginine mutant.
AB  - The two major intermediate filament proteins in glandular epithelia are keratin
      polypeptides 8 and 18 (K8/18). To evaluate the function and potential disease
      association of K18, we examined the effects of mutating a highly conserved
      arginine (arg89) of K18. Expression of K18 arg89-->his/cys and its normal K8
      partner in cultured cells resulted in punctate staining as compared with the
      typical filaments obtained after expression of wild-type K8/18. Generation of
      transgenic mice expressing human K18 arg89-->cys resulted in marked disruption of
      liver and pancreas keratin filament networks. The most prominent histologic
      abnormalities were liver inflammation and necrosis that appeared at a young age
      in association with hepatocyte fragility and serum transaminase elevation. These
      effects were caused by the mutation since transgenic mice expressing wild-type
      human K18 showed a normal phenotype. A relative increase in the phosphorylation
      and glycosylation of detergent solubilized K8/18 was also noted in vitro and in
      transgenic animals that express mutant K18. Our results indicate that the highly
      conserved arg plays an important role in glandular keratin organization and
      tissue fragility as already described for epidermal keratins. Phosphorylation and
      glycosylation alterations in the arg mutant keratins may account for some of the
      potential changes in the cellular function of these proteins. Mice expressing
      mutant K18 provide a novel animal model for human chronic hepatitis, and for
      studying the tissue specific function(s) of K8/18.

PMID- 8522592
TI  - Axonal transport of mitochondria along microtubules and F-actin in living
      vertebrate neurons.
AB  - A large body of evidence indicates that microtubules (MTs) conduct organelle
      transport in axons, but recent studies on extruded squid axoplasm have suggested
      that actin microfilaments (MFs) may also play a role in this process. To
      investigate the separate contributions to transport of each class of cytoskeletal
      element in intact vertebrate axons, we have monitored mitochondrial movements in
      chick sympathetic neurons experimentally manipulated to eliminate MTs, MFs, or
      both. First, we grew neurons in the continuous presence of: (a) cytochalasin E to
      create neurites which had never contained MFs; or (b) nocodazole or vinblastine
      to produce neurites which had never contained MTs. Mitochondria moved
      bidirectionally at normal velocities along the length of neurites which contained
      MTs and lacked MFs, but did not even enter neurites grown without MTs but
      containing MFs. In a second approach, we treated established neuronal cultures
      with cytoskeletal drugs to disrupt either MTs or MFs in axons already containing
      mitochondria. In cytochalasin-treated cells, which retained MTs but lacked MFs,
      average mitochondrial velocity increased in both directions, but net directional
      transport decreased. In vinblastine-treated cells, which lacked MTs but retained
      essentially normal levels of MFs, mitochondria continued to move bidirectionally
      but the average mitochondrial velocity and excursion length were reduced for both
      directions of movement, and the mitochondria spent threefold as much time moving
      in the retrograde as in the anterograde direction, resulting in net retrograde
      transport. Treatment of established cultures with both drugs produced neurites
      lacking MTs and MFs but still rich in neurofilaments; these showed a striking
      absence of any mitochondrial motility. These data indicate that axonal organelle
      transport can occur along both MTs and MFs in vivo, but with different velocities
      and net transport properties.

PMID- 8522593
TI  - Interaction of tau with the neural plasma membrane mediated by tau's amino
      terminal projection domain.
AB  - The neuronal microtubule-associated protein tau is required for the development
      of cell polarity in cultured neurons. Using PC12 cells that stably express tau
      and tau amino-terminal fragments, we report that tau interacts with the neural
      plasma membrane through its amino-terminal projection domain. In differentiated
      PC12 transfectants, tau is found in growth cone-like structures in a
      nonmicrotubule-dependent manner. In hippocampal neurons, tau is differentially
      extracted by detergent and enriched in the growth cone and the distal axon when
      membrane is left intact. In PC12 transfectants, overexpression of tau's amino
      terminal fragment, but not of full-length tau, suppresses NGF-induced process
      formation. Our data suggest that tau's amino-terminal projection domain has an
      important role in neuritic development and establishes tau as a mediator of
      microtubule-plasma membrane interactions.

PMID- 8522594
TI  - Adaptation of nicotinic acetylcholine receptor, myogenin, and MRF4 gene
      expression to long-term muscle denervation.
AB  - Muscle activity alters the expression of functionally distinct nicotinic
      acetylcholine receptors (nAChR) via regulation of subunit gene expression.
      Denervation increases the expression of all subunit genes and promotes the
      expression of embryonic-type (alpha 2 beta delta gamma) nAChRs, while electrical
      stimulation of denervated muscle prevents this induction. We have discovered that
      the denervation-induced increases in alpha, beta, gamma, and delta subunit gene
      expression do not persist in muscles that have been denervated for periods
      extending beyond a couple of months. However, expression of RNA encoding the
      epsilon-subunit remains elevated suggesting a return to expression of
      predominantly adult-type (alpha 2 beta delta epsilon) nAChR in long-term
      denervated muscles; a finding confirmed by single channel patch-clamp analysis.
      Since the nAChR subunit genes are regulated by the MyoD family of muscle
      regulatory factors, and the genes encoding these factors are also induced
      following short-term muscle denervation, we determined their level of expression
      in long-term denervated muscle. Although MyoD and myf-5 RNA levels remained
      elevated, myogenin and MRF4 RNAs were induced only transiently by muscle
      denervation. Surprisingly, Id-1, a negative regulator of transcription, was
      gradually induced in denervated muscle with RNA levels peaking about two months
      after denervation. It is likely that this maintained level of increased Id
      expression, in conjunction with the returning levels of myogenin and MRF4
      expression, account for the reduced level of embryonic receptors in long-term
      denervated muscle. These changing patterns of gene expression may have important
      consequences for the ability of muscle to recover function after denervation.

PMID- 8522595
TI  - Constitutive expression of calreticulin in osteoblasts inhibits mineralization.
AB  - Recent studies have shown that the multifunctional protein calreticulin can
      localize to the cell nucleus and regulate gene transcription via its ability to
      bind a protein motif in the DNA-binding domain of nuclear hormone receptors. A
      number of known modulators of bone cell function, including vitamin D, act
      through this receptor family, suggesting that calreticulin may regulate their
      action in bone cells. We have used a gain-of-function strategy to examine this
      putative role of calreticulin in MC3T3-E1 osteoblastic cells. Purified
      calreticulin inhibited the binding of the vitamin D receptor to characterized
      vitamin D response elements in gel retardation assays. This inhibition was due to
      direct protein-protein interactions between the vitamin D receptor and
      calreticulin. Expression of calreticulin transcripts declined during MC3T3-E1
      osteoblastic differentiation. MC3T3-E1 cells were transfected with calreticulin
      expression vectors; stably transfected cell lines overexpressing recombinant
      calreticulin were established and assayed for vitamin D-induced gene expression
      and the capacity to mineralize. Constitutive calreticulin expression inhibited
      basal and vitamin D-induced expression of the osteocalcin gene, whereas
      osteopontin gene expression was unaffected. This pattern mimicked the gene
      expression pattern observed in parental cells before down-regulation of
      endogenous calreticulin expression. In long-term cultures of parental or vector
      transfected cells, 1 alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) induced a two- to
      threefold stimulation of 45Ca accumulation into the matrix layer. Constitutive
      expression of calreticulin inhibited the 1,25(OH)2D3-induced 45Ca accumulation.
      This result correlated with the complete absence of mineralization nodules in
      long-term cultures of calreticulin-transfected cells. These data suggest that
      calreticulin can regulate bone cell function by interacting with specific nuclear
      hormone receptor-mediated pathways.

PMID- 8522596
TI  - A cell biological perspective on genome research.

PMID- 8522597
TI  - Chromatin conformation and salt-induced compaction: three-dimensional structural
      information from cryoelectron microscopy.
AB  - Cryoelectron microscopy has been used to examine the three-dimensional (3-D)
      conformation of small oligonucleosomes from chicken erythrocyte nuclei after
      vitrification in solutions of differing ionic strength. From tilt pairs of
      micrographs, the 3-D location and orientation of the nucleosomal disks, and the
      paths of segments of exposed linker can be obtained. In "low-salt" conditions (5
      mM NaCl, 1 mM EDTA, pH 7.5), the average trinucleosome assumes the shape of an
      equilateral triangle, with nucleosomes at the vertices, and a length of exposed
      linker DNA between consecutive nucleosomes equivalent to approximately 46 bp. The
      two linker DNA segments converge at the central nucleosome. Removal of histones
      H1 and H5 results in a much more variable trinucleosome morphology, and the two
      linker DNA segments usually join the central nucleosome at different locations.
      Trinucleosomes vitrified in 20 mM NaCl, 1 mM EDTA, (the salt concentration
      producing the maximal increase in sedimentation), reveal that compaction occurs
      by a reduction in the included angle made by the linker DNA segments at the
      central nucleosome, and does not involve a reduction in the distance between
      consecutive nucleosomes. Frequently, there is also a change in morphology at the
      linker entry-exit site. At 40 mM NaCl, there is no further change in
      trinucleosome morphology, but polynucleosomes are appreciably more compact.
      Nevertheless, the 3-D zig-zag conformation observed in polynucleosomes at low
      salt is retained at 40 mM NaCl, and individual nucleosome disks remain separated
      from each other. There is no evidence for the formation of solenoidal
      arrangements within polynucleosomes. Comparison of the solution conformation of
      individual oligonucleosomes with data from physical measurements on bulk
      chromatin samples suggests that the latter should be reinterpreted. The new data
      support the concept of an irregular zig-zag chromatin conformation in solution
      over a range of ionic strengths, in agreement with other in situ (McDowall, A.W.,
      J.M. Smith, and J. Dubochet. 1986, EMBO (Eur. Mol. Biol. Organ.) J.5: 1395-1402;
      Horowitz, R.A., D.A. Agard, J.W. Sedat, and C.L. Woodcock, 1994. J. Cell Biol.
      125:1-10), and in vitro conclusions (van Holde, K., and J. Zlatanova. 1995. J.
      Biol. Chem. 270:8373-8376). Cryoelectron microscopy also provides a way to
      determine the 3-D conformation of naturally occurring chromatins in which precise
      nucleosome positioning plays a role in transcriptional regulation.

PMID- 8522598
TI  - Sac1p mediates the adenosine triphosphate transport into yeast endoplasmic
      reticulum that is required for protein translocation.
AB  - Protein translocation into the yeast endoplasmic reticulum requires the transport
      of ATP into the lumen of this organelle. Microsomal ATP transport activity was
      reconstituted into proteoliposomes to characterize and identify the transporter
      protein. A polypeptide was purified whose partial amino acid sequence
      demonstrated its identity to the product of the SAC1 gene. Accordingly,
      microsomal membranes isolated from strains harboring a deletion in the SAC1 gene
      (sac1 delta) were found to be deficient in ATP-transporting activity as well as
      severely compromised in their ability to translocate nascent prepro-alpha-factor
      and preprocarboxypeptidase Y. Proteins isolated from the microsomal membranes of
      a sac1 delta strain were incapable of stimulating ATP transport when
      reconstituted into the in vitro assay system. When immunopurified to homogeneity
      and incorporated into artificial lipid vesicles, Sac1p was shown to reconstitute
      ATP transport activity. Consistent with the requirement for ATP in the lumen of
      the ER to achieve the correct folding of secretory proteins, the sac1 delta
      strain was shown to have a severe defect in transport of procarboxypeptidase Y
      out of the ER and into the Golgi complex in vivo. The collective data indicate an
      intimate role for Sac1p in the transport of ATP into the ER lumen.

PMID- 8522599
TI  - Anterograde and retrograde traffic between the rough endoplasmic reticulum and
      the Golgi complex.
AB  - The transfer of newly synthesized membrane proteins moving from the rough
      endoplasmic reticulum (RER) to the Golgi complex has been studied by electron
      microscopy in HEp-2 cells transfected with cDNAs for chimeric proteins. These
      proteins consist of a reporter enzyme, horseradish peroxidase (HRP), anchored to
      the transmembrane domains of two integral membrane proteins, the transferrin
      receptor and sialyl-transferase. The chimeras are distributed throughout the
      nuclear envelope, RER, vesicular tubular clusters (VTCs) and a network of tubules
      in the cis-Golgi area. At 20 degrees C tubules containing chimera connect the RER
      to the VTCs and to the cis-Golgi network. On transfer to 37 degrees C in the
      presence of dithiothreitol (DTT), the chimeras are seen to move from the RER and
      through the Golgi stack. With this temperature shift the direct connections with
      the RER are lost and free vesicles form; some of these vesicles contain HRP
      reaction product which is much more concentrated than in the adjacent RER while
      others lack reaction product entirely. In cells expressing SSHRPKDEL, DAB
      reaction product remains distributed throughout the RER, the VTCs, and the cis
      Golgi network for prolonged periods in the presence of DTT and almost all of the
      vesicles which form at 37 degrees C are DAB-positive. Together these observations
      demonstrate that all three chimeras are transported from the RER to the cis-Golgi
      in free, 40-60-nm vesicles at 37 degrees C. They also suggest that the retrograde
      traffic which carries SSHRPKDEL back to the RER is probably mediated by vesicles
      with a similar morphology but which, in cells expressing membrane-anchored
      chimeras, lack detectable reaction product.

PMID- 8522600
TI  - Misfolded major histocompatibility complex class I molecules accumulate in an
      expanded ER-Golgi intermediate compartment.
AB  - Misfolded membrane proteins are rapidly degraded, often shortly after their
      synthesis and insertion in the endoplasmic reticulum (ER), but the exact location
      and mechanisms of breakdown remain unclear. We have exploited the requirement of
      MHC class I molecules for peptide to achieve their correct conformation: peptide
      can be withheld by introducing a null mutation for the MHC-encoded peptide
      transporter, TAP. By withholding TAP-dependent peptides, the vast majority of
      newly synthesized class I molecules fails to leave the endoplasmic reticulum and
      is degraded. We used mice transgenic for HLA-B27 on a TAP1-deficient background
      to allow visualization by immunoelectron microscopy of misfolded HLA-B27
      molecules in thymic epithelial cells. In such HLA transgenic animals, the TAP
      mutation can be considered a genetic switch that allows control over the extent
      of folding of the protein of interest, HLA-B27, while the rate of synthesis of
      the constituent subunits remains unaltered. In TAP1-deficient, HLA-B27 transgenic
      animals, HLA-B27 molecules fail to assemble correctly, and do not undergo
      carbohydrate modifications associated with the Golgi apparatus, such as
      conversion to Endoglycosidase H resistance, and acquisition of sialic acids. We
      show that such molecules accumulate in an expanded network of tubular and
      fenestrated membranes. This compartment has its counterpart in normal thymic
      epithelial cells, and is identified as an ER-Golgi intermediate. We detect the
      presence of ubiquitin and ubiquitin-conjugating enzymes in association with this
      compartment, suggesting a nonlysosomal mode of degradation of its contents.

PMID- 8522601
TI  - Caveolin cycles between plasma membrane caveolae and the Golgi complex by
      microtubule-dependent and microtubule-independent steps.
AB  - Caveolin is a protein associated with the characteristic coats that decorate the
      cytoplasmic face of plasma membrane caveolae. Recently it was found that exposure
      of human fibroblasts to cholesterol oxidase (CO) rapidly induces caveolin to
      redistribute to the ER and then to the Golgi complex, and that subsequent removal
      of CO allows caveolin to return to the plasma membrane (Smart, E. J., Y.-S. Ying,
      P. A. Conrad, R. G. W. Anderson, J. Cell Biol. 1994, 127:1185-1197). We now
      present evidence that caveolin normally undergoes microtubule-dependent cycling
      between the plasma membrane and the Golgi. In cells that were treated briefly
      with nocodazole and then with a mixture of nocodazole plus CO, caveolin relocated
      from the plasma membrane to the ER and then to the ER/Golgi intermediate
      compartment (ERGIC), but subsequent movement to the Golgi was not observed. Even
      in the absence of CO, nocodazole caused caveolin to accumulate in the ERGIC.
      Nocodazole did not retard the movement of caveolin from the Golgi to the plasma
      membrane after removal of CO. Incubation of cells at 15 degrees followed by
      elevation of the temperature to 37 degrees caused caveolin to accumulate first in
      the ERGIC and then in the Golgi, before finally reestablishing its normal steady
      state distribution predominantly in plasma membrane caveolae. In cells released
      from a 15 degrees block, movement of caveolin from the Golgi to the plasma
      membrane was not inhibited by nocodazole. Taken together, these results imply
      that caveolin cycles constitutively between the plasma membrane and the Golgi by
      a multi-step process, one of which, ERGIC-to-Golgi transport, requires
      microtubules. This novel, bidirectional pathway may indicate roles for
      microtubules in the maintenance of caveolae, and for caveolin in shuttling fatty
      acids and cholesterol between the plasma membrane and the ER/Golgi system.

PMID- 8522602
TI  - Rab 7: an important regulator of late endocytic membrane traffic.
AB  - Rab5 and rab7 proteins belong to a superfamily of small molecular weight GTPases
      known to be associated with early and late endosomes, respectively. The rab5
      protein plays an important regulatory role in early endocytosis, yet the function
      of rab7 protein was previously uncharacterized. This question was addressed by
      comparing the kinetics of vesicular stomatitis virus (VSV) G protein
      internalization in baby hamster kidney cells overexpressing wild-type or dominant
      negative mutant forms of the rab7 protein (rab7N125I and rab7T22N).
      Overexpression of wild-type rab7 protein allowed normal transport to late
      endosomes (mannose 6-phosphate receptor positive), while the rab7N125I mutant
      caused the VSV G protein to accumulate specifically in early (transferrin
      receptor positive) endosomes. Horseradish peroxidase and paramyxovirus SV5
      hemagglutinin-neuraminidase (HN) were used in quantitative biochemical assays to
      further demonstrate that rab7 function was not required for early internalization
      events, but was crucial in downstream degradative events. The characteristic
      cleavage of SV5 HN in the late endosome distinguishes internalization from
      transport to later stages of the endocytic pathway. Mutant rab7N125I or rab7T22N
      proteins had no effect on the internalization of either horseradish peroxidase or
      SV5 HN protein. In contrast, the mutant proteins markedly inhibited the
      subsequent cleavage of the SV5 HN protein. Taken together, these data support a
      key role for rab7, downstream of rab5, in regulating membrane transport leading
      from early to late endosomes. We compare our findings to those obtained for the
      yeast homologues Ypt51p, Ypt52p, Ypt53p, and Ypt7p.

PMID- 8522603
TI  - Pay32p of the yeast Yarrowia lipolytica is an intraperoxisomal component of the
      matrix protein translocation machinery.
AB  - Pay mutants of the yeast Yarrowia lipolytica fail to assemble functional
      peroxisomes. One mutant strain, pay32-1, has abnormally small peroxisomes that
      are often found in clusters surrounded by membraneous material. The functionally
      complementing gene PAY32 encodes a protein, Pay32p, of 598 amino acids (66,733 D)
      that is a member of the tetratricopeptide repeat family. Pay32p is
      intraperoxisomal. In wild-type peroxisomes, Pay32p is associated primarily with
      the inner surface of the peroxisomal membrane, but approximately 30% of Pay32p is
      localized to the peroxisomal matrix. The majority of Pay32p in the matrix is
      complexed with two polypeptides of 62 and 64 kD recognized by antibodies to SKL
      (peroxisomal targeting signal-1). In contrast, in peroxisomes of the pay32-1
      mutant, Pay32p is localized exclusively to the matrix and forms no complex.
      Biochemical characterization of the mutants pay32-1 and pay32-KO (a PAY32 gene
      disruption strain) showed that Pay32p is a component of the peroxisomal
      translocation machinery. Mutations in the PAY32 gene prevent the translocation of
      most peroxisome-bound proteins into the peroxisomal matrix. These proteins,
      including the 62-kD anti-SKL-reactive polypeptide, are trapped in the peroxisomal
      membrane at an intermediate stage of translocation in pay32 mutants. Our results
      suggest that there are at least two distinct translocation machineries involved
      in the import of proteins into peroxisomes.

PMID- 8522604
TI  - Studies of the interaction between titin and myosin.
AB  - The interaction of titin with myosin has been studied by binding assays and
      electron microscopy. Electron micrographs of the titin-myosin complex suggest a
      binding site near the tip of the tail of the myosin molecule. The distance from
      the myosin head-tail junction to titin indicates binding 20-30 nm from the myosin
      COOH terminus. Consistent with this, micrographs of titin-light meromyosin (LMM)
      show binding near the end of the LMM molecule. Plots of myosin- and LMM
      attachment positions along the titin molecule show binding predominantly in the
      region located in the A band in situ, which is consistent with the proposal that
      titin regulates thick filament assembly. Estimates of the apparent dissociation
      constant of the titin-LMM complex were approximately 20 nM. Assays of LMM
      cyanogen bromide fragments also suggested a strong binding site near the COOH
      terminus. Proteolysis of a COOH-terminal 17.6-kD CNBr fragment isolated from
      whole myosin resulted in eight peptides of which only one, comprising 17
      residues, bound strongly to titin. Two isoforms of this peptide were detected by
      protein sequencing. Similar binding data were obtained using synthetic versions
      of both isoforms. The peptide is located immediately COOH-terminal of the fourth
      "skip" residue in the myosin tail, which is consistent with the electron
      microscopy. Skip-4 may have a role in determining thick filament structure, by
      allowing abrupt bending of the myosin tail close to the titin-binding site.

PMID- 8522605
TI  - Actin filaments in yeast are unstable in the absence of capping protein or
      fimbrin.
AB  - Many actin-binding proteins affect filament assembly in vitro and localize with
      actin in vivo, but how their molecular actions contribute to filament assembly in
      vivo is not understood well. We report here that capping protein (CP) and fimbrin
      are both important for actin filament assembly in vivo in Saccharomyces
      cerevisiae, based on finding decreased actin filament assembly in CP and fimbrin
      mutants. We have also identified mutations in actin that enhance the CP phenotype
      and find that those mutants also have decreased actin filament assembly in vivo.
      In vitro, actin purified from some of these mutants is defective in
      polymerization or binding fimbrin. These findings support the conclusion that CP
      acts to stabilize actin filaments in vivo. This conclusion is particularly
      remarkable because it is the opposite of the conclusion drawn from recent studies
      in Dictyostelium (Hug, C., P.Y. Jay, I. Reddy, J.G. McNally, P.C. Bridgman, E.L.
      Elson, and J.A. Cooper. 1995. Cell. 81:591-600). In addition, we find that the
      unpolymerized pool of actin in yeast is very small relative to that found in
      higher cells, which suggests that actin filament assembly is less dynamic in
      yeast than higher cells.

PMID- 8522606
TI  - Ponticulin plays a role in the positional stabilization of pseudopods.
AB  - Ponticulin is a 17-kD glycoprotein that represents a major high affinity link
      between the plasma membrane and the cortical actin network of Dictyostelium. To
      assess the role of ponticulin in pseudopod extension and retraction, the motile
      behavior of two independently generated mutants lacking ponticulin was analyzed
      using computer-assisted two- and three-dimensional motion analysis systems. More
      than half of the lateral pseudopods formed off the substratum by ponticulin-minus
      cells slipped relative to the substratum during extension and retraction. In
      contrast, all pseudopods formed off the substratum by wild-type cells were
      positionally fixed in relation to the substratum. Ponticulin-minus cells also
      formed a greater proportion of both anterior and lateral pseudopods off the
      substratum and absorbed a greater proportion of lateral pseudopods into the
      uropod than wild-type cells. In a spatial gradient of cAMP, ponticulin-minus
      cells were less efficient in tracking the source of chemoattractant. Since
      ponticulin-minus cells extend and retract pseudopods with the same time course as
      wild-type cells, these behavioral defects in ponticulin-minus cells appear to be
      the consequence of pseudopod slippage. These results demonstrate that pseudopods
      formed off the substratum by wild-type cells are positionally fixed in relation
      to the substratum, that ponticulin is required for positional stabilization, and
      that the loss of ponticulin and the concomitant loss of positional stability of
      pseudopods correlate with a decrease in the efficiency of chemotaxis.

PMID- 8522607
TI  - Cytoplasmic dynein binds dynactin through a direct interaction between the
      intermediate chains and p150Glued.
AB  - Cytoplasmic dynein is a retrograde microtubule motor thought to participate in
      organelle transport and some aspects of minus end-directed chromosome movement.
      The mechanism of binding to organelles and kinetochores is unknown. Based on
      homology with the Chlamydomonas flagellar outer arm dynein intermediate chains
      (ICs), we proposed a role for the cytoplasmic dynein ICs in linking the motor
      protein to organelles and kinetochores. In this study two different IC isoforms
      were used in blot overlay and immunoprecipitation assays to identify IC-binding
      partners. In overlays of complex protein samples, the ICs bound specifically to
      polypeptides of 150 and 135 kD, identified as the p150Glued doublet of the
      dynactin complex. In reciprocal overlay assays, p150Glued specifically recognized
      the ICs. Immunoprecipitations from total Rat2 cell extracts, rat brain cytosol,
      and rat brain membranes further identified the dynactin complex as a specific
      target for IC binding. using truncation mutants, the sites of interaction were
      mapped to amino acids 1-123 of IC-1A and amino acids 200-811 of p150Glued. While
      cytoplasmic dynein and dynactin have been implicated in a common pathway by
      genetic analysis, our findings identify a direct interaction between two specific
      component polypeptides and support a role for dynactin as a dynein "receptor".
      Our data also suggest, however, that this interaction must be highly regulated.

PMID- 8522608
TI  - The Chlamydomonas kinesin-like protein FLA10 is involved in motility associated
      with the flagellar membrane.
AB  - The Chlamydomonas FLA10 gene was shown to encode a flagellar kinesin-like protein
      (Walther, Z., M. Vashishtha, and J.L. Hall. 1994. J. Cell Biol. 126:175-188). By
      using a temperature-sensitive allele of FLA10, we have determined that the FLA10
      protein is necessary for both the bidirectional movement of polystyrene beads on
      the flagellar membrane and intraflagellar transport (IFT), the bidirectional
      movement of granule-like particles beneath the flagellar membrane (Kozminski,
      K.G., K.A. Johnson, P. Forscher, and J.L. Rosenbaum. 1993. Proc. Natl. Acad. Sci.
      (USA). 90:5519-5523). In addition, we have correlated the presence and position
      of the IFT particles visualized by light microscopy with that of the electron
      dense complexes (rafts) observed beneath the flagellar membrane by electron
      microscopy. A role for FLA10 in submembranous or flagellar surface motility is
      also strongly supported by the immunolocalization of FLA10 to the region between
      the axonemal outer doublet microtubules and the flagellar membrane.

PMID- 8522609
TI  - Fission yeast cell morphogenesis: identification of new genes and analysis of
      their role during the cell cycle.
AB  - To identify new genes involved in the control of cell morphogenesis in the
      fission yeast Schizosaccharomyces pombe we have visually screened for temperature
      sensitive mutants that show defects in cell morphology. We have isolated and
      characterized 64 mutants defining 19 independent genes, 10 of which have not been
      previously described. One class of mutants, defining 12 orb genes, become round
      and show a complete loss of cell polarity. A second class of mutants exhibits
      branched or bent morphologies. These mutants show defects in either selection of
      the growth site, defining two tea genes, or in the maintenance of growth
      direction, defining five ban genes. Immunofluorescence analysis of these
      morphological mutants shows defects in the organization of the microtubule and
      actin cytoskeleton. These defects include shortened, bundled, and asymmetrically
      localized microtubules and enlarged and mislocalized actin patches. Analysis of
      the mutant phenotypes has allowed us to order the genes into four groups
      according to their function during the cell cycle: genes required for the
      maintenance of cell polarity throughout the cell cycle; genes necessary only for
      the reestablishment of cell polarity after mitosis and not for maintaining cell
      polarity once it is established; genes essential for the transition from
      monopolar to bipolar growth and genes that severe as 'polarity markers'.

PMID- 8522610
TI  - A localized elevation of cytosolic free calcium is associated with cytokinesis in
      the zebrafish embryo.
AB  - Cytokinesis, a key step in cell division, is known to be precisely regulated both
      in its timing and location. At present, the regulatory mechanism of cytokinesis
      is not well understood, although it has been suggested that calcium signaling may
      play an important role in this process. To test this notion, we introduced a
      sensitive fluorescent Ca2+ indicator into the zebrafish embryo and used confocal
      microscopy to measure the spatiotemporal variation of intracellular free Ca2+
      concentration ([Ca2+]i) during cell cleavage. It was evident that a localized
      elevation of [Ca2+]i is closely associated with cytokinesis. First, we found that
      during cytokinesis, the level of free Ca2+ was elevated locally precisely at the
      cleavage site. Second, the rise of free Ca2+ was very rapid and occurred just
      preceding the initiation of furrow contraction. These observations strongly
      suggest that cytokinesis may be triggered by a calcium signal. In addition, we
      found that this cytokinesis-associated calcium signal arose mainly from internal
      stores of Ca2+ rather than from external free Ca2+; it could be blocked by the
      antagonist of inositol trisphosphate (InsP3) receptors. These findings suggest
      that the localized elevation of [Ca2+]i is caused by the release of free Ca2+
      from the endoplasmic reticulum through the InsP3-regulated calcium channels.

PMID- 8522611
TI  - An amino-terminal extension is required for the secretion of chick agrin and its
      binding to extracellular matrix.
AB  - Agrin is an extracellular matrix (ECM) protein with a calculated relative
      molecular mass of more than 200 kD that induces the aggregation of acetylcholine
      receptors (AChRs) at the neuromuscular junction. This activity has been mapped to
      its COOH terminus. In an attempt to identify the functions of the NH2-terminal
      end, we have now characterized full-length chick agrin. We show that chick agrin
      encoded by a previously described cDNA is not secreted from transfected cells.
      Secretion is achieved with a construct that includes an additional 350 bp derived
      from the 5' end of chick agrin mRNA. Recombinant agrin is a heparan sulfate
      proteoglycan (HSPG) of more than 400 kD with glycosaminoglycan side chains
      attached only to the NH2-terminal half. Endogenous agrin in tissue homogenates
      also has an apparent molecular mass of > 400 kD. While the amino acid sequence
      encoded by the 350-bp extension has no homology to published rat agrin, it
      includes a stretch of 15 amino acids that is 80% identical to a previously
      identified bovine HSPG. The extension is required for binding of agrin to ECM.
      AChR aggregates induced by recombinant agrin that includes the extension are
      considerably smaller than those induced by agrin fragments, suggesting that
      binding of agrin to ECM modulates the size of receptor clusters. In addition, we
      found a site encoding seven amino acids at the NH2-terminal end of agrin that is
      alternatively spliced. While motor neurons express the splice variant with the
      seven amino acid long insert, muscle cells mainly synthesize isoforms that lack
      this insert. In conclusion, the cDNAs described here code for chick agrin that
      has all the characteristics previously allocated to endogenous agrin.

PMID- 8522612
TI  - Adequate connexin-mediated coupling is required for proper insulin production.
AB  - To assess whether connexin (Cx) expression contributes to insulin secretion, we
      have investigated normal and tumoral insulin-producing cells for connexins, gap
      junctions, and coupling. We have found that the glucose-sensitive cells of
      pancreatic islets and of a rat insulinoma are functionally coupled by gap
      junctions made of Cx43. In contrast, cells of several lines secreting insulin
      abnormally do not express Cx43, gap junctions, and coupling. After correction of
      these defects by stable transfection of Cx43 cDNA, cells expressing modest levels
      of Cx43 and coupling, as observed in native beta-cells, showed an expression of
      the insulin gene and an insulin content that were markedly elevated, compared
      with those observed in both wild-type (uncoupled) cells and in transfected cells
      overexpressing Cx43. These findings indicate that adequate levels of Cx-mediated
      coupling are required for proper insulin production and storage.

PMID- 8522613
TI  - Hepatocyte growth factor/scatter factor induces a variety of tissue-specific
      morphogenic programs in epithelial cells.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is the mesenchymal ligand of the
      epithelial tyrosine kinase receptor c-Met. In vitro, HGF/SF has morphogenic
      properties, e.g., induces kidney epithelial cells to form branching ducts in
      collagen gels. Mutation of the HGF/SF gene in mice results in embryonic lethality
      due to severe liver and placenta defects. Here, we have evaluated the morphogenic
      activity of HGF/SF with a large variety of epithelial cells grown in three
      dimensional collagen matrices. We found that HGF/SF induces SW 1222 colon
      carcinoma cells to form crypt-like structures. In these organoids, cells exhibit
      apical/basolateral polarity and build a well-developed brush border towards the
      lumen. Capan 2 pancreas carcinoma cells, upon addition of HGF/SF, develop large
      hollow spheroids lined with a tight layer of polarized cells. Collagen inside the
      cysts is digested and the cells show features of pancreatic ducts. HGF/SF induces
      EpH4 mammary epithelial cells to form long branches with end-buds that resemble
      developing mammary ducts. pRNS-1-1 prostate epithelial cells in the presence of
      HGF/SF develop long ducts with distal branching as found in the prostate.
      Finally, HGF/SF simulates alveolar differentiation in LX-1 lung carcinoma cells.
      Expression of transfected HGF/SF cDNA in LX-1 lung carcinoma and EpH4 mammary
      epithelial cells induce morphogenesis in an autocrine manner. In the cell lines
      tested, HGF/SF activated the Met receptor by phosphorylation of tyrosine
      residues. These data show that HGF/SF induces intrinsic, tissue-specific
      morphogenic activities in a wide variety of epithelial cells. Apparently, HGF/SF
      triggers respective endogenous programs and is thus an inductive, not an
      instructive, mesenchymal effector for epithelial morphogenesis.

PMID- 8522614
TI  - Massive programmed cell death in intestinal epithelial cells induced by three
      dimensional growth conditions: suppression by mutant c-H-ras oncogene expression.
AB  - Deregulation of molecular pathways controlling cell survival and death, including
      programmed cell death, are thought to be important factors in tumor formation,
      disease progression, and response to therapy. Studies devoted to analyzing the
      role of programmed cell death in cancer have been carried out primarily using
      conventional monolayer cell culture systems. However the majority of cancers grow
      as three-dimensional solid tumors. Because gene expression, and possibly
      function, can be significantly altered under such conditions, we decided to
      analyze the control and characteristics of cell death using a compatible three
      dimensional tissue culture system (multicellular spheroids) and compare the
      results obtained to those using two-dimensional monolayer cell culture. To do so
      we selected for study an immortalized, but nontumorigenic line of rat intestinal
      epithelial cells, called IEC-18, and several tumorigenic variants of IEC-18
      obtained by transfection with a mutant (activated) c-H-ras oncogene. The
      rationale for choosing these cell lines was based in part on the fact that
      intestinal epithelial cells grow in vivo in a monolayer-like manner and form
      solid tumors only after sustaining certain genetic mutations, including those
      involving the ras gene family. We found that the IEC-18 cells, which grow readily
      and survive in monolayer cell culture, undergo massive cell death within 48-72 h
      when cultured as multicellular spheroids on a nonadhesive surface. This process
      was accompanied by a number of features associated with programmed cell death
      including chromatin condensation (Hoechst 33258 staining) apoptotic morphology,
      DNA degradation, and a virtual complete loss of colony forming (clonogenic)
      ability in the absence of apparent membrane damage as well as accumulation of
      lipid containing vacuoles in the cytoplasm. Moreover, enforced over-expression of
      a transfected bcl-2 gene could prevent this cell death process from taking place.
      In marked contrast, three different stably transfected ras clones of IEC-18
      survived when grown as multicellular spheroids. In addition, an IEC cell line
      (called clone 25) carrying its mutant transfected ras under a glucocorticoid
      inducible promoter survived in three-dimensional culture only when the cells were
      exposed to dexamethasone. If exposure to dexamethasone was delayed for as long as
      48 h the cells nevertheless survived, whereas the cells became irreversibly
      committed to programmed cell death (PCD) if exposed to dexamethasone after 72 h.
      These results suggest that intestinal epithelial cells may be programmed to
      activate a PCD pathway upon detachment from a physiologic two-dimensional
      monolayer configuration, and that this process of adhesion regulated programmed
      cell death (ARPCD) can be substantially suppressed by expression of a mutant ras
      oncogene.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8522615
TI  - Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the
      subepithelial matrix with gradients chemotactic for neutrophils.
AB  - During intestinal disease induced by Salmonella typhimurium transepithelial
      migration of neutrophils (PMN) rapidly follows attachment of the bacteria to the
      epithelial apical membrane. Among the events stimulated by these interactions is
      the release of chemotaxins that guide PMN through the subepithelial matrix and
      subsequently through the epithelium itself (McCormick, B.A., S.P. Colgan, C. Delp
      Archer, S.I. Miller, and J.L. Madara. 1993. J. Cell Biol. 123:895-907). Given the
      substantial volume flow that normally characterizes matrix compartments
      underlying transporting epithelia, it is unclear how such transmatrix signaling
      is sustained. Here we show that when underlying matrices are isolated from
      biophysically confluent polarized monolayers of the human intestinal epithelial
      cell line T84, they fail to support substantial transmatrix migration of PMN
      unless an exogenous chemotactic gradient is imposed. In contrast, such matrices
      isolated from confluent monolayers apically colonized with S. typhimurium support
      spontaneous transmatrix migration of PMN. Such chemotactic imprinting of
      underlying matrices is resistant to volume wash and is paralleled by secretion of
      the known matrix-binding chemokine IL-8. Chemotactic imprinting of the matrix
      underlying S. typhimurium-colonized monolayers is dependent on epithelial protein
      synthesis, is directional implying the existence of a gradient, and is
      neutralized by antibodies either to IL-8 or to the IL-8 receptor on PMN. An
      avirulent S. typhimurium strain, PhoPc, which attaches to epithelial cells as
      efficiently as wild-type S. typhimurium, fails to induce basolateral secretion of
      IL-8 and likewise fails to imprint matrices. Together, these observations show
      that the epithelial surface can respond to the presence of a luminal pathogen and
      subsequently imprint the subepithelial matrix with retained IL-8 gradients
      sufficient to resist washout effects of the volume flow that normally traverses
      this compartment. Such data further support the notion that the primary role for
      basolateral secretion of IL-8 by the intestinal and likely other epithelia is
      recruitment of PMN through the matrix to the subepithelial space, rather than
      directing the final movement of PMN across the epithelium.

PMID- 8522616
TI  - alpha-2 Macroglobulin receptor/Ldl receptor-related protein(Lrp)-dependent
      internalization of the urokinase receptor.
AB  - The GPI-anchored urokinase plasminogen activator receptor (uPAR) does not
      internalize free urokinase (uPA). On the contrary, uPAR-bound complexes of uPA
      with its serpin inhibitors PAI-1 (plasminogen activator inhibitor type-1) or PN-1
      (protease nexin-1) are readily internalized in several cell types. Here we
      address the question whether uPAR is internalized as well upon binding of uPA
      serpin complexes. Both LB6 clone 19 cells, a mouse cell line transfected with the
      human uPAR cDNA, and the human U937 monocytic cell line, express in addition to
      uPAR also the endocytic alpha 2-macroglobulin receptor/low density lipoprotein
      receptor-related protein (LRP/alpha 2-MR) which is required to internalize uPAR
      bound uPA-PAI-1 and uPA-PN-1 complexes. Downregulation of cell surface uPAR
      molecules in U937 cells was detected by cytofluorimetric analysis after uPA-PAI-1
      and uPA-PN-1 incubation for 30 min at 37 degrees C; this effect was blocked by
      preincubation with the ligand of LRP/alpha 2-MR, RAP (LRP/alpha 2-MR-associated
      protein), known to block the binding of the uPA complexes to LRP/alpha 2-. MR.
      Downregulation correlated in time with the intracellular appearance of uPAR as
      assessed by confocal microscopy and immuno-electron microscopy. After 30 min
      incubation with uPA-PAI-1 or uPA-PN-1 (but not with free uPA), confocal
      microscopy showed that uPAR staining in permeabilized LB6 clone 19 cells moved
      from a mostly surface associated to a largely perinuclear position. This effect
      was inhibited by the LRP/alpha 2-MR RAP. Perinuclear uPAR did not represent newly
      synthesized nor a preexisting intracellular pool of uPAR, since this fluorescence
      pattern was not modified by treatment with the protein synthesis inhibitor
      cycloheximide, and since in LB6 clone 19 cells all of uPAR was expressed on the
      cell surface. Immuno-electron microscopy confirmed the plasma membrane to
      intracellular translocation of uPAR, and its dependence on LRP/alpha 2-MR in LB6
      clone 19 cells only after binding to the uPA-PAI-1 complex. After 30 min
      incubation at 37 degrees C with uPA-PAI-1, 93% of the specific immunogold
      particles were present in cytoplasmic vacuoles vs 17.6% in the case of DFP-uPA.
      We conclude therefore that in the process of uPA-serpin internalization, uPAR
      itself is internalized, and that internalization requires the LRP/alpha 2-MR.

PMID- 8522617
TI  - Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced
      exons.
AB  - The hyaluronan (HA)-binding function (lectin function) of the leukocyte homing
      receptor, CD44, is tightly regulated. Herein we address possible mechanisms that
      regulate CD44 isoform-specific HA binding. Binding studies with melanoma
      transfectants expressing CD44H, CD44E, or with soluble immunoglobulin fusions of
      CD44H and CD44E (CD44H-Rg, CD44E-Rg) showed that although both CD44 isoforms can
      bind HA, CD44H binds HA more efficiently than CD44E. Using CD44-Rg fusion
      proteins we show that the variably spliced exons in CD44E, V8-V10, specifically
      reduce the lectin function of CD44, while replacement of V8-V10 by an ICAM-1
      immunoglobulin domain restores binding to a level comparable to that of CD44H.
      Conversely, CD44 bound HA very weakly when exons V8-V10 were replaced with a CD34
      mucin domain, which is heavily modified by O-linked glycans. Production of CD44E
      Rg or incubation of CD44E-expressing transfectants in the presence of an O-linked
      glycosylation inhibitor restored HA binding to CD44H-Rg and to cell surface CD44H
      levels, respectively. We conclude that differential splicing provides a
      regulatory mechanism for CD44 lectin function and that this effect is due in part
      to O-linked carbohydrate moieties which are added to the Ser/Thr rich regions
      encoded by the variably spliced CD44 exons. Alternative splicing resulting in
      changes in protein glycosylation provide a novel mechanism for the regulation of
      lectin activity.

PMID- 8522618
TI  - CHORTLES: a method for representing oligomeric and template-based mixtures.
AB  - Screening mixtures of synthetic oligomers or fixed templates (e.g., rings) with
      varying substituents is increasingly the focus of drug discovery programs.
      CHORTLES is designed and implemented to facilitate representation, storage, and
      searching of oligomeric and template-based mixtures of any size. Building upon
      the CHUCKLES method of representing oligomers as both monomer-based sequences and
      all-atom structures, CHORTLES compactly represents a mixture without explicitly
      enumerating individual molecules. This method lends itself to a hierarchy
      relating mixtures to submixtures and individual compounds, as one finds when
      deconvoluting mixtures in drug lead discovery programs. In addition, we describe
      two methods of searching mixtures at the monomer level. We also present a simple
      pictorial representation for describing all components in a mixture, which
      becomes essential as the list of monomer names is expanded beyond common names
      (e.g., amino acids).

PMID- 8522619
TI  - Chronic obstructive pulmonary disease: progress nevertheless.

PMID- 8522620
TI  - ECG complexes that resemble tombstones.

PMID- 8522621
TI  - Domestic violence.

PMID- 8522622
TI  - Solutions for patients with erectile dysfunction.

PMID- 8522623
TI  - Open access to behavioral health care.

PMID- 8522624
TI  - Ophthalmoscopic and cardiac abnormalities in an asymptomatic elderly woman.

PMID- 8522625
TI  - Preeclampsia: not simply pregnancy-induced hypertension.
AB  - Once classified as a seizure disorder and later as a hypertensive condition,
      preeclampsia is actually a multisystem disease. It remains a leading cause of
      maternal and neonatal morbidity. Clinical challenges include identifying patients
      who are at risk of serious complications and deciding whether it is safer for the
      fetus to be delivered or to remain in the uterus.

PMID- 8522626
TI  - Steps toward gene therapy: 2. Cancer and AIDS.
AB  - Strategies under investigation--in some cases in clinical trials--include the
      delivery of "suicide genes" to induce the self-destruction of infected or
      tumorous cells and the delivery of genes to facilitate T-cell recognition of such
      cells. The HIV life cycle offers many additional attack points for therapeutic
      genes designed to prevent the expression of viral genes or to impede the function
      of essential HIV proteins.

PMID- 8522627
TI  - The elderly patient with multiple complaints.
AB  - "Thick chart" patients often have both a stated and an unstated agenda. Failure
      to recognize the latter can create a crisis of confidence that may prompt the
      patient to search for a more empathetic physician. So in addition to making a
      diagnosis in the face of confusing data, the physician must establish confidence
      by listening carefully and involving the patient in treatment decisions.

PMID- 8522628
TI  - Case in point. Cardiac tamponade.

PMID- 8522629
TI  - Severe paroxysmal coughing and pleuritic pain in an adult.

PMID- 8522630
TI  - Management of hypertensive urgencies and emergencies.
AB  - Hypertensive emergency is a condition in which there is elevation of both
      systolic and diastolic blood pressure with the presence of acute target organ
      disease. Hypertensive urgency is a condition where the blood pressure is elevated
      (diastolic > 120 mmHg) with the absence of acute target organ disease.
      Hypertensive emergencies are best managed with parenteral drugs and careful
      intraarterial blood pressure monitoring. Hydralazine has been widely used in
      treatment of hypertension in eclampsia and preeclampsia, and its safety has been
      demonstrated in these patients. Sodium nitroprusside (SNP) has the most reliable
      antihypertensive activity, which begins immediately after its administration and
      ends when the infusion is stopped. As with diazoxide, it should be used with
      caution in patients with impaired cerebral flow. SNP is the preferred drug in
      obtaining controlled hypotension in patients undergoing neurovascular surgery.
      Intravenous nitroglycerin is useful in patients prone to myocardial ischemia, but
      should be avoided in patients with increased intracranial pressure. Esmolol is
      effective in controlling both supraventricular tachyarrhythmias and severe
      hypertension. Its short onset of duration of action make it useful in the
      emergent setting, but because of its negative inotropic effect its use should be
      avoided in patients with low cardiac output. Verapamil should not be used in
      patients with preexisting conduction abnormalities. Nicardipine is a potent
      arteriolar vasodilator without a significant direct depressant effect on
      myocardium. As with other afterload reducing agents, it should not be used in
      patients with severe aortic stenosis. Because angiotensin-converting enzyme (ACE)
      inhibitors generally cause cerebral vasodilatation, enalaprilat may be
      particularly beneficial for patients who are at high risk of developing cerebral
      hypotensive episodes secondary to impaired cerebral circulation. Fenoldopam, a
      selective post-synaptic dopaminergic receptor (DA1) has been shown to be
      effective in treating severe hypertension with a lower incidence of side effects
      than SNP. Hypertensive urgencies can usually be managed with oral agents. Oral
      nifedipine, captopril, clonidine, labetalol, prazosin, and nimodipine have all
      been shown to be effective in these situations.

PMID- 8522631
TI  - Effective half-life in clinical pharmacology.

PMID- 8522632
TI  - Effects of phenytoin on plasma high-density lipoprotein cholesterol levels in men
      with low levels of high-density lipoprotein cholesterol.
AB  - A low level of high-density lipoprotein cholesterol (HDL-C) is an important and
      common risk factor for coronary heart disease. Cross-sectional studies and
      uncontrolled clinical trials have suggested that phenytoin can significantly
      raise HDL-C levels. This study was undertaken to determine whether phenytoin can
      raise HDL-C levels in men with low levels of HDL-C. Ninety-two men currently
      receiving outpatient care at a Veterans Affairs medical center and with baseline
      HDL-C levels < or = 1.16 mmol/L (45 mg/dL) were recruited to participate in this
      randomized, placebo-controlled, double-blind clinical trial. Participants
      received a placebo or 100 mg, 200 mg, or 300 mg of phenytoin once daily for 14
      weeks. Lipid levels were measured at baseline and at 6, 10, and 14 weeks. After
      14 weeks of treatment, the 200-mg and 300-mg phenytoin groups together achieved a
      significant 10% increase in HDL-C levels compared with placebo after adjusting
      for differences in baseline HDL-C levels, age, and body mass index. Other lipid
      levels did not significantly change in the phenytoin groups compared with
      placebo. Average compliance was 98% or greater for each of the treatment groups.
      Eighteen participants dropped out of the study with similar numbers from each
      treatment group. Side effects were mild and mostly transient. Low doses of
      phenytoin are well tolerated and can effectively increase HDL-C levels in men
      with low levels of HDL-C.

PMID- 8522633
TI  - Effect of losartan, an angiotensin II receptor antagonist, on response of
      cortisol and aldosterone to adrenocorticotrophic hormone.
AB  - Many imidazole derivatives are shown to inhibit adrenal steroid biosynthesis. The
      present study was undertaken to examine an effect of another imidazole
      derivative, losartan (an angiotensin II receptor antagonist), on responses of
      cortisol and aldosterone to adrenocorticotrophic hormone (ACTH). Nine patients
      with essential hypertension were given placebo orally for 7 days and 50 mg of
      losartan for the next 9 days. Response of serum cortisol and plasma aldosterone
      to intramuscular ACTH injection were determined before and at the end of the
      treatment with losartan. Serum cortisol and plasma aldosterone significantly
      increased after ACTH injection in both periods of treatment (placebo and
      losartan). The increments in these parameters during treatment with losartan were
      not significantly different from those during treatment with placebo. These
      results suggest that the inhibitory effect of losartan on adrenal steroid
      biosynthesis is negligible.

PMID- 8522634
TI  - Antianginal and antiischemic efficacy of monotherapy extended-release nisoldipine
      (Coat Core) in chronic stable angina.
AB  - A double-blind, randomized, placebo-controlled study was conducted to test the
      peak and trough antianginal and antiischemic monotherapy efficacy and safety of a
      new extended-release formulation of nisoldipine (nisoldipine Coat Core [Bayer
      Corporation], 20 mg, 40 mg, and 60 mg once daily compared to placebo). Study
      patients had a history of chronic, stable angina pectoris, exercise-induced
      angina in association with ST segment depression, and exercise test
      reproducibility. Of the 483 patients enrolled in the study, results were valid
      for safety analysis for 312 and for efficacy analysis for 284. There was a
      statistically significant improvement in total exercise time at both peak and
      trough for patients taking 20 mg and 60 mg of nisoldipine compared with patients
      taking placebo, but the group taking 60 mg was not better than the group taking
      20 mg (33.9 and 33.7 seconds, respectively, at trough). The results were similar
      for the secondary endpoints (time to onset of angina and time to 1 mm ST segment
      depression). No correlation was evident between plasma nisoldipine levels and
      total exercise duration. Headache and peripheral edema were the most frequently
      reported adverse events and were dose related. There were no discontinuations due
      to adverse events in patients randomized to the 20-mg nisoldipine group. No
      deaths occurred while patients were receiving active nisoldipine therapy. Therapy
      with this extended-release formulation of nisoldipine is an effective once-daily
      treatment for chronic stable angina pectoris. It represents one of the few
      dihydropyridine calcium channel antagonists that has shown efficacy when
      administered as monotherapy to patients with angina.

PMID- 8522635
TI  - Invasive pharmacodynamics of fosinopril in patients with congestive heart
      failure.
AB  - Five patients with NYHA Class III CHF received 5 mg of fosinopril on each of 4
      days. Hemodynamics were measured with a Swan-Ganz catheter after dosing on day 1.
      Measurements of plasma fosinoprilat, ACE activity, renin, and aldosterone were
      obtained. An Emax model was used to fit the effect-site concentration and mean
      arterial pressure change. A linear model was used to fit the effect-site
      concentration and the pulmonary artery wedge pressure (PAWP) change. At steady
      state on day 4, AUC0-24 was 1668 +/- 476 ng.hr/mL and Cmax was 143.5 +/- 33.6
      ng/mL. The mean elimination half-life of fosinoprilat was 11.3 +/- 0.7 hours, and
      median Tmax occurred at 3 hours, corresponding to maximum plasma ACE inhibition.
      Plasma renin activity was unchanged, and mean plasma aldosterone level declined.
      Emax modeling using fosinoprilat concentrations and mean arterial pressure showed
      good prediction of the pharmacodynamic effects from the effect-site
      concentration. A linear relationship was observed between the effect-site
      concentrations of fosinoprilat and PAWP. When expressed in an Emax model, the
      pharmacodynamic actions of fosinopril in patients with CHF are a reflection of
      its pharmacokinetics.

PMID- 8522636
TI  - Moexipril in the treatment of mild to moderate essential hypertension: comparison
      with sustained-release verapamil.
AB  - To compare and contrast the antihypertensive efficacy of an angiotensin
      converting enzyme (ACE) inhibitor to a calcium antagonist, 88 and 90 patients
      with essential hypertension were randomly assigned to receive moexipril and
      verapamil, respectively. At the end of the first 6 weeks of active therapy,
      sitting diastolic blood pressure decreased by 11 mmHg in patients receiving
      moexipril and by 9 mmHg in patients receiving verapamil. The 24-week treatment
      period was completed by 72 patients who received moexipril and 71 patients who
      received verapamil. Mean decreases in sitting diastolic blood pressure of 10 mmHg
      and 11 mmHg were observed in the respective intent-to-treat moexipril and
      verapamil groups. At doses of 7.5 mg and 15 mg once daily, moexipril had an
      antihypertensive effect comparable to that of sustained-release verapamil at
      doses of 180 mg and 240 mg once daily.

PMID- 8522637
TI  - The safety and tolerance of xanomeline tartrate in patients with Alzheimer's
      disease.
AB  - Xanomeline tartrate (active ingredient xanomeline) is a muscarinic agonist that
      has demonstrated specificity for the M1 receptor in preclinical studies and has
      been well tolerated at dosages up to 50 mg three times a day in healthy elderly
      subjects. To define the maximum tolerated dose (MTD) of xanomeline tartrate in
      patients with Alzheimer's disease, 48 patients (20 men, 28 women) with probable
      Alzheimer's disease were enrolled in a double-blind, placebo-controlled inpatient
      study to determine the safety and tolerability of 8 fixed dosages of xanomeline
      tartrate (25, 35, 50, 60, 75, 90, 100, and 115 mg, all three times a day) given
      for 7 days. For each dosage the treatment panel consisted of six patients (four
      taking xanomeline tartrate and two taking placebo). With the discontinuation of
      two patients because of severe intolerable adverse events, a minimum intolerated
      dose was reached at 115 mg three times a day, and 100 mg three times a day was
      defined as the MTD. This MTD in patients was two-fold greater than the MTD
      previously determined in healthy elderly volunteers.

PMID- 8522638
TI  - Effect of aging on atenolol pharmacokinetics and pharmacodynamics.
AB  - A study was conducted to characterize and compare the pharmacodynamics and
      pharmacokinetics of atenolol in young and elderly men. Six young (mean +/- SD,
      25.0 +/- 3.0 years) and six elderly (63.0 +/- 3.2 years) healthy men took
      atenolol 100 mg orally once daily for 6 days. Heart rate response to submaximal
      exercise was measured at selected times for 48 hours, and plasma and urine
      samples were collected over the same time interval. The Sigmoid Emax model was
      fit to percent reductions in exercise heart rate and atenolol plasma
      concentrations. The younger men had significantly lower values for area under the
      steady-state plasma concentration-time curve and higher values for systemic
      clearance/F and renal clearance. EC50 values showed a trend toward greater
      sensitivity to the negative chronotropic effects of atenolol among the elderly
      men. Model-derived percent reductions in heart rate were greater at all
      concentrations among the elderly men. These data suggest that group differences
      in atenolol pharmacokinetics were likely a result of age-related decline in renal
      function, and that the elderly subjects were at least as sensitive as, and maybe
      even more sensitive than, the younger subjects to the negative chronotropic
      effects of atenolol.

PMID- 8522639
TI  - Pharmacokinetics of lansoprazole in hemodialysis patients.
AB  - The pharmacokinetics of the new benzimidazole proton pump inhibitor lansoprazole
      and five of its metabolites were assessed after single oral dose administration
      to five hemodialysis patients. Patients were studied on dialysis and nondialysis
      days. Multiple blood and dialysate samples were collected after dosing and were
      assayed for lansoprazole and metabolite content via high-performance liquid
      chromatography. The degree of lansoprazole plasma protein binding was lower in
      hemodialysis patients than in subjects with normal renal function or patients
      with renal impairment not requiring dialytic therapy, although this tended to
      moderate when assessed immediately after dialysis. Examination of venous plasma
      concentration, paired arterial-venous concentration, and dialysate data revealed
      that lansoprazole and its metabolites were poorly dialyzable. No dosage
      adjustment of lansoprazole is necessary in hemodialysis patients nor is
      supplementation after hemodialysis sessions necessary.

PMID- 8522640
TI  - Pharmacokinetics and pharmacodynamics of Ro 41-3696, a novel nonbenzodiazepine
      hypnotic.
AB  - This report describes the first evaluation in humans of Ro 41-3696. Based on its
      preclinical profile, Ro 41-3696, a nonbenzodiazepine partial agonist at the
      benzodiazepine receptor, offers promising perspectives as an innovative hypnotic
      drug in that it does not exhibit most of the disadvantages associated with full
      agonists. Single oral doses of 0.1, 0.3, 1.0, 3.0, 10, and 30 mg were
      administered sequentially to six groups of six healthy male volunteers in a
      placebo-controlled, double-blind design. Tolerability was assessed and
      pharmacokinetic and pharmacodynamic measurements were conducted during a period
      of 28 hours after drug intake. Ro 41-3696 was well tolerated at all doses,
      causing no clinically relevant changes in vital signs or laboratory parameters.
      At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central
      nervous system depressant effect. Pharmacokinetic analyses revealed that Ro 41
      3696 was absorbed and eliminated rapidly (tmax = approximately 1 hour; t1/2 =
      approximately 4 hours). At all times plasma levels of Ro 41-3290, the
      desethylated derivative of Ro 41-3696, were higher than those of the parent drug
      (tmax and t1/2 values = approximately 2 and 8 hours, respectively). Area under
      the curve (AUC) data indicated dose-proportional pharmacokinetics for both Ro 41
      3696 and Ro 41-3290. Performance in both a tracking and a memory search test was
      significantly affected by doses of 10 and 30 mg, and long-term memory, as
      assessed by a word learning and recall test, was slightly impaired at these
      doses. The results of this study support the initiation of therapeutic efficacy
      studies with Ro 41-3696 in doses up to approximately 5 mg and further exploration
      of the characteristics of Ro 41-3290.

PMID- 8522641
TI  - Nonlinear pharmacokinetics of nefazodone after escalating single and multiple
      oral doses.
AB  - The single- and multiple-dose pharmacokinetics of nefazodone and its metabolites,
      hydroxynefazodone, p-hydroxynefazodone, and m-chlorophenylpiperazine were
      investigated in two groups of 18 healthy male volunteers, employing three-period
      complete crossover designs. In one group, single 50-mg, 100-mg, and 200-mg oral
      doses of nefazodone hydrochloride were administered with a 1-week washout between
      treatments. In the other group, doses of 50 mg, 100 mg, and 200 mg were
      administered twice a day (every 12 hours) for 7.5 days (15 doses) with a 1-week
      washout between treatments. Serial plasma samples were obtained in both groups
      and assayed for nefazodone, hydroxynefazodone, m-chlorophenylpiperazine, and p
      hydroxynefazodone. Cmax plasma levels of nefazodone and hydroxynefazodone were
      attained within 2 hours of administration of nefazodone; tmax for m
      chlorophenylpiperazine was more delayed, and p-hydroxynefazodone levels were
      generally below the assay limit. On repeated twice-daily dosing of nefazodone,
      steady-state levels of the drug and its metabolites were reached within 3 days.
      Mean single-dose plasma half-life (t1/2) values for nefazodone increased from
      approximately 1 hour at a 50-mg dose to approximately 2 hours at a 200-mg dose;
      at steady state, t1/2 values increased from approximately 2 hours at 50 mg twice
      daily to approximately 3.7 hours at 200 mg twice daily. Whereas dose increased in
      the proportion of 1:2:4, mean single-dose AUC0-infinity for nefazodone increased
      in the proportion of 1:3.3:8.9 and mean steady-state AUC0-tau for nefazodone
      increased in the proportion of 1:4.2:16.8. Plasma levels of hydroxynefazodone
      paralleled those of nefazodone and were approximately 33% of nefazodone levels at
      each dose level. Plasma levels of m-chlorophenylpiperazine were only
      approximately 10% those of nefazodone. Within the dosage range of 50-200 mg of
      nefazodone hydrochloride, nefazodone and hydroxynefazodone exhibited nonlinear
      pharmacokinetics; m-chlorophenylpiperazine, a minor metabolite, appeared to
      exhibit linear pharmacokinetics.

PMID- 8522642
TI  - The influence of reduced dietary fat absorption induced by orlistat on the
      pharmacokinetics of digoxin in healthy volunteers.
AB  - To assess the influence of an orlistat-induced reduction in dietary fat
      absorption on the pharmacokinetics of digoxin, an open-label, placebo-controlled,
      randomized, two-way crossover study was performed in 12 healthy volunteers. Each
      subject received single 0.4-mg doses of digoxin (soft gelatin capsules)
      administered orally on the fourth day of orlistat (120 mg three times daily for 6
      days) and placebo (three times daily for 6 days) treatment, separated by at least
      an 11-day washout period. Serial blood samples were collected before and at
      appropriate intervals after each digoxin dose to determine plasma concentrations
      of unchanged digoxin. The 90% confidence intervals for the ratio of geometric
      least-squares means (for Cmax, AUC0-48, AUC0-t, and AUC) and for the difference
      of arithmetic least-squares means (for tmax and lambda z) indicate that the
      pharmacokinetics of digoxin was not altered by treatment with orlistat. This
      results suggests that a approximately 30% reduction in dietary fat absorption
      will not change the efficacy of digoxin in cardiac patients.

PMID- 8522643
TI  - Distribution of parvalbumin-immunoreactive cells and fibers in the human
      amygdaloid complex.
AB  - The calcium-binding protein, parvalbumin, was localized immunohistochemically in
      the human amygdaloid complex. Neuronal cell bodies and fibers that are
      immunoreactive to parvalbumin were observed in most of the amygdaloid nuclei and
      cortical areas. Three types of immunoreactive aspiny neurons, ranging from small
      spherical cells (type 1) to large multipolar cells (type 2) and fusiform cells
      (type 3), were observed. The densities of the types of neurons that were
      parvalbumin-immunoreactive varied in the different regions of the amygdala. The
      highest densities of parvalbumin-immunoreactive neurons were observed in the
      lateral nucleus, in the magnocellular and intermediate divisions of the basal
      nucleus, in the magnocellular division of the accessory basal nucleus and in the
      amygdalohippocampal area. The regions containing the lowest density of
      parvalbumin-immunoreactive cells were the paralaminar nucleus, the parvicellular
      division of the basal nucleus, the central nucleus, the medial nucleus and the
      anterior cortical nucleus. In general, the distribution of immunoreactive fibers
      and terminals paralleled that of immunoreactive cells. Parvalbumin-immunoreactive
      varicose fibers formed basket-like plexi and cartridges around the unstained
      neurons, which suggests that parvalbumin is located in GABAergic basket cells and
      chandelier cells, respectively. The distribution of parvalbumin-immunoreactive
      profiles in the human amygdaloid complex was similar to, rather than different
      from that previously reported in the monkey amygdala (Pitkanen and Amaral [1993]
      J. Comp. Neurol. 331:14-36). This study provides baseline information about the
      organization of GABAergic inhibitory circuitries in the human amygdaloid complex.

PMID- 8522644
TI  - Organization of projections from the medial nucleus of the amygdala: a PHAL study
      in the rat.
AB  - The organization of axonal projections from the four recognized parts of the
      medial amygdalar nucleus (MEA) were characterized with the Phaesolus vulgaris
      leucoagglutinin (PHAL) method in male rats. The results indicate that the MEA
      consists of two major divisions, ventral and dorsal, and that the former may also
      consist of rostral and caudal regions. As a whole, the MEA generates centrifugal
      projections to several parts of the accessory and main olfactory sensory
      pathways, and projections to a) several parts of the intrahippocampal circuit
      (ventrally); b) the ventral striatum, ventral pallidum, and bed nuclei of the
      stria terminalis (BST) in the basal telencephaon; c) many parts of the
      hypothalamus; d) midline and medial parts of the thalamus; and e) the
      periaqueductal gray, ventral tegmental area, and midbrain raphe. The dorsal
      division of the MEA (the posterodorsal part) is characterized by projections to
      the principal nucleus of the BST, and to the anteroventral periventricular,
      medial, and central parts of the medial preoptic, and ventral premammillary
      hypothalamic nuclei. These hypothalamic nuclei project heavily to neuroendocrine
      and autonomic-related parts of the hypothalamic periventricular zone. The ventral
      division of the MEA (the anterodorsal, anteroventral, and posteroventral parts)
      is characterized by dense projections to the transverse and interfascicular
      nuclei of the BST, and to the lateral part of the medial preoptic, anterior
      hypothalamic, and ventromedial hypothalamic nuclei. However, dorsal regions of
      the ventral division provide rather dense inputs to the medial preoptic region
      and capsule of the ventromedial nucleus, whereas ventral regions of the ventral
      division preferentially innervate the anterior hypothalamic, dorsomedial, and
      ventral parts of the ventromedial nuclei. Functional evidence suggests that
      circuits associated with dorsal regions of the ventral division may deal with
      reproductive behavior, whereas circuits associated with ventral regions of the
      ventral division may deal preferentially with agonistic behavior.

PMID- 8522645
TI  - Cholecystokinin activates catecholaminergic neurons in the caudal medulla that
      innervate the paraventricular nucleus of the hypothalamus in rats.
AB  - Stimulation of gastric vagal afferents by systemic administration of
      cholecystokinin octapeptide (CCK) inhibits gastric motility, reduces food intake,
      and stimulates pituitary secretion of oxytocin and adrenocorticotropic hormone in
      rats. To characterize further the central neural circuits responsible for these
      effects, the present study used triple-labeling immunocytochemical methods to
      determine whether or not exogenous CCK activates cFos expression in
      catecholaminergic neurons in the caudal medulla that project to the
      paraventricular nucleus of the hypothalamus (PVN). To identify these neurons, the
      retrograde tracer fluorogold (FG) was iontophoresed into the PVN of anesthetized
      rats under stereotaxic guidance. After 2 weeks, rats were injected with CCK (100
      micrograms/kg, i.p.) and then anesthetized and killed 1 hour later by perfusion
      fixation. Medullary sections were processed for triple immunocytochemical
      localization of cFos, retrogradely transported FG, and tyrosine hydroxylase (TH).
      In rats with FG injections centered in the PVN (n = 10), approximately 70% of the
      FG-labeled neurons in the caudal nucleus of the solitary tract (NST) and
      ventrolateral medulla (VLM) expressed cFos. Of these activated PVN-projecting
      neurons, approximately 78% in the NST and 89% in the VLM were catecholaminergic
      (TH positive). These results indicate that PVN-projecting catecholaminergic
      neurons within the caudal medulla are activated by peripheral administration of
      CCK, further implicating these ascending catecholaminergic pathways in the
      neuroendocrine, physiological, and behavioral effects produced by gastric vagal
      stimulation.

PMID- 8522646
TI  - Muller glial cells of the tree shrew retina.
AB  - The tree shrew is one of the few mammalian species whose retinae are strongly
      cone dominated, which is usually the case in reptilian and avian retinae. Muller
      cells of the tree shrew (Tupaia belangeri) retina were studied by transmission
      electron microscopy of tissue sections and freeze-fracture replicas, by
      immunolabeling of the intermediate filament protein vimentin in radial paraffin
      sections and in whole retinae, as well as by intracellular dye injection in
      slices of retinae. In addition, enzymatically isolated cells were stained by
      Pappenheim's panoptic staining method. The cells showed an ultrastructure that is
      similar to other mammalian Muller cells with two exceptions: Due to the extensive
      lateral fins of cone inner segments, the apical microvilli of Muller cells are
      arranged in peculiar palisades, and the basket-like Muller cell sheaths around
      neuronal somata in both nuclear layers consist of unusual multilayered membrane
      lamellae. Unlike Muller cells in other mammalian species studied thus far, but
      similar to reptilian and avian Muller cells, those of tree shrews commonly have
      two or more vitread processes rather than one main trunk. Muller cell densities
      range between some 13,000 mm-2 in the periphery and about 20,000 mm-2 in the
      retinal center. Neuron:(Muller)glial cell ratios were estimated to be 7.9:1 in
      the center and 6.2:1 in the periphery. For each Muller cell, about 1.5 (cone)
      photoreceptor cells, four or five interneurons of the inner nuclear layer, and
      about one cell of the ganglion cell layer were counted. This is a much lower
      number of neurons per Muller cell than in most other mammals studied.

PMID- 8522647
TI  - Independent efferent populations in the nucleus of the optic tract: an anatomical
      and physiological study in rat and cat.
AB  - The efferent projections of the nucleus of the optic tract (NOT) and dorsal
      terminal nucleus of the accessory optic system (DTN) to the contralateral NOT
      DTN, ipsilateral inferior olive (IO), ipsilateral nucleus prepositus hypoglossi
      (NPH), and ipsilateral dorsal lateral geniculate nucleus (LGNd) were examined in
      pigmented rats and in cats by using anterograde and retrograde tract tracing, as
      well as extracellular recording and electrical stimulation. Anterograde tracing
      in the rat revealed a dense termination field of NOT-DTN efferents throughout the
      homologous contralateral territory. In both species three different cell
      populations, projecting to the contralateral NOT-DTN, ipsilateral IO, and
      ipsilateral LGNd, respectively, were distinguished by means of multiple
      retrograde tracing. No clear topographical segregation of the different NOT-DTN
      relay cell populations was observed. On the other hand, a large proportion (at
      least 60%) of NOT-DTN neurons projecting to the ipsilateral NPH were found to
      bifurcate upon the IO in the rat. Electrophysiologically, NOT-DTN neurons
      projecting to the IO were identified by their directionally selective responses.
      Such neurons were never activated by electrical stimulation of either the
      contralateral NOT-DTN or the ipsilateral LGNd. Neurons antidromically activated
      from the contralateral NOT-DTN could not be activated from the ipsilateral LGNd.
      Thus, in both cat and rat the NOT-DTN includes at least three independent relay
      cell populations. As a consequence, the NOT-DTN must serve functions additional
      to the generation of eye movements during optokinetic nystagnus, a function
      subserved by the directionally selective NOT-DTN cells.

PMID- 8522648
TI  - Fos expression induced by changes in arterial pressure is localized in distinct,
      longitudinally organized columns of neurons in the rat midbrain periaqueductal
      gray.
AB  - The distribution of neurons expressing Fos within the periaqueductal gray (PAG)
      following pharmacologically induced high or low blood pressure was examined to
      determine (1) if PAG neurons are responsive to changes in arterial pressure (AP)
      and (2) the relationship of these cells to the functionally defined hypertensive
      and hypotensive columns in PAG. Changes in AP differentially induced robust Fos
      expression in neurons confined to discrete, longitudinally organized columns
      within PAG. Increased AP produced extensive Fos-like immunoreactivity within the
      lateral PAG, beginning at the level of the oculomotor nucleus. At the level of
      the dorsal raphe, Fos expression induced by increased AP shifted dorsally, into
      the dorsolateral division of PAG; this pattern of Fos labeling was maintained
      throughout the caudal one-third of PAG. Double-labeling for Fos and nicotinamide
      adenine dinucleotide phosphate diaphorase confirmed that Fos-positive cells
      induced by increased AP were located in the dorsolateral division of PAG at these
      caudal levels. Fos positive cells were codistributed, but not colocalized, with
      nicotinamide adenine dinucleotide phosphate diaphorase-positive cells. Decreased
      AP evoked a completely different pattern of Fos expression. Fos-positive cells
      were predominantly located within the ventrolateral PAG region, extending from
      the level of the trochlear nucleus through the level of the caudal dorsal raphe.
      Double-labeling studies for Fos and serotonin indicated that only 1-2 double
      labeled cells per section were present. Saline infusion resulted in very few Fos
      like immunoreactive cells, indicating that volume receptor activation does not
      account for Fos expression in PAG evoked by changes in AP. These results indicate
      that (1) substantial numbers of PAG neurons are excited by pharmacologically
      induced changes in AP and (2) excitatory barosensitive PAG neurons are
      anatomically segregated based on their responsiveness to a specific directional
      change in AP.

PMID- 8522649
TI  - Orthograde axonal transport studies of projections from the zona incerta and
      pretectum to the basilar pontine nuclei in the rat.
AB  - This study employed orthogradely transported axonal tracers to demonstrate, in
      the rat, projections that reach the basilar pontine nuclei from the zona incerta
      or pretectal nuclei. Except for the most rostral levels, all subdivisions of the
      zona incerta give rise to substantive basilar pontine projections. Although some
      topographic differences exist among the temination patterns of various
      subdivisions, no clear somatotopically organized scheme is apparent. Most
      incertopontine axons descend to the basilar pons in association with fibers of
      the medial lemniscus or crus cerebri and reach ipsilateral ventral and medial
      pontine gray regions. A sparse number of terminals are evident in the
      contralateral medial pontine gray. The anterior pretectal axons also descend with
      the medial lemniscus and crus cerebri to enter exclusively the ipsilateral
      basilar pons where they terminate most densely in ventral and medial regions.
      Dual orthograde labeling experiments indicate that some pretectal terminal fields
      in the pontine gray are shared with incertopontine projections and with afferents
      from the dorsal column nuclei. This potential convergence of basilar pontine
      afferent projections is significant in light of 1) the known somatosensory input
      to the zona incerta and pretectum and 2), the fractured somatotopy of peripheral
      cutaneous inputs that arrive in the cerebellar cortex via mossy fibers. The
      present studies also employed electron microscopy to identify synaptic boutons
      formed by incerto- and pretectopontine axons, and they proved to be remarkably
      similar. Each is a medium to small-sized bouton that contains spheroidal synaptic
      vesicles and forms asymmetric membrane specializations. Most incerto- and
      pretectopontine boutons participate in glomerular synaptic complexes that include
      a single, centrally located bouton contacted on its perimeter by several types of
      dendritic profiles including shafts and spine-like appendages. A relatively small
      number of labeled boutons of either type contacts single, isolated dendritic
      elements in the neuropil. Taken together, these findings suggest that some
      basilar pontine neurons might receive convergent inputs from the zona incerta and
      pretectum as well as other somatosensory-related systems such as the dorsal
      column nuclei and sensorimotor cortex.

PMID- 8522650
TI  - Laminar pattern of termination of the ipsilateral cortical projection from SII to
      SI in cats.
AB  - The present light and electron microscopic experiments were carried out on the
      first somatic sensory area (SI) of cats to determine the laminar distribution of
      axon terminals from the ipsilateral second somatic sensory area (SII) and to
      identify the types of synapses between these terminals and the neuronal elements
      of SI. Phaseolus vulgaris-leucoagglutinin (PHA-L) was iontophoretically injected
      into multiple sites and at different cortical depths of the forepaw
      representation zone of SII. Fixed brain blocks containing the injected SII and
      ipsilateral SI were cut into slices and processed immunocytochemically to stain
      PHA-L-filled fibers and terminals. Light microscopic examination of SI revealed
      patches of anterograde labeling in the forepaw representation zone, concentrated
      mainly in supragranular layers. In these layers, thin immunolabeled fibers
      branched extensively and formed a dense plexus that was more prominent in layers
      II and I. Conversely, the infragranular layers contained fragments of vertically
      oriented thick fibers that rarely emitted axon collaterals. PHA-L-labeled axons
      had numerous swellings along their course, interpreted as boutons en passant, and
      stalked boutons. Of 19,661 labeled terminals (17,833 beads and 1,828 stalked
      boutons), 84.74% were observed in supragranular layers, with the highest
      concentration in layer II (33.15%) and lower in layers I (26.27%) and III
      (25.30%). The proportion of terminals was lower in layers IV (6.49%) and V
      (5.45%) and lowest in layer VI (3.32%). These counts also showed that boutons en
      passant were the majority (90.70%) and stalked boutons, the minority (9.30%). The
      ratio of these two types of presynaptic specializations was similar (9:1) in all
      six layers. Electron microscopic examination of the labeled regions of SI showed
      that both axon swellings and stalked boutons formed synapses of the asymmetric
      type with SI neuronal elements. The majority (85.37%) of a sample of 130 labeled
      terminals synapsed on SI neurons in layers I-III. The identified postsynaptic
      profiles were dendritic spines (61.11%) or medium-sized and small dendrites
      (38.89%). These results are discussed in relation to those of a companion study
      on the laminar pattern of the projection from SI to SII of cats (P. Barbaresi, A.
      Minelli, and T. Manzoni, 1994, J. Comp. Neurol. 343:582-596). Based on the
      anatomical organization of these reciprocal connections, there seems to be no
      clear hierarchicalal relationship between SI and SII in cats.

PMID- 8522651
TI  - Noradrenergic system in the chicken brain: immunocytochemical study with
      antibodies to noradrenaline and dopamine-beta-hydroxylase.
AB  - A light microscopic immunocytochemical study, using antisera against
      noradrenaline (NA) and dopamine-beta-hydroxylase (DBH), revealed the
      noradrenergic system in the brain of the chicken (Gallus domesticus). NA- and DBH
      immunoreactive (ir) elements showed a similar distribution throughout the whole
      brain. The neurons immunoreactive for the monoamine were confined to the lower
      brainstem, the pons, and the medulla. In the pons, a rather dense group of cells
      was found in the dorsal, most posterior part of the locus coeruleus and in the
      caudal nucleus subcoeruleus ventralis. A few labeled cells appeared in and around
      the nucleus olivaris superior in the most caudal part of the metencephalic
      tegmentum. In the medulla oblongata, noradrenergic cells could be visualized at
      the level of the nucleus of the solitary tract and in a ventrolateral complex.
      Virtually all regions of the brain contained a rather dense innervation by NA-
      and DBH-immunopositive varicose fibers. Noradrenergic fibers and terminals were
      especially abundant in the ventral forebrain and in the periventricular
      hypothalamic regions. DBH-ir and NA-ir fibers, varicosities, and punctate
      structures could be observed in close association with immunonegative perikarya
      in several brain regions, more specifically in the ventral telencephalon, in the
      mid- and tuberal hypothalamic region, and in the dorsal rostral pons. Some
      perikarya in these brain areas were completely surrounded by noradrenergic
      structures that formed pericellular arrangements around the cells. The present
      study on the distribution of the noradrenergic system in the brain of the chicken
      combined with the results of a previous report on the distribution of L-Dopa and
      dopamine in the same species (L. Moons, J. van Gils, E. Ghijsels, and F.
      Vandesande, 1994, J. Comp. Neurol. 346:97-118) offers the opportunity to
      differentiate between the various catecholamines in the brain of this vertebrate.
      The results are discussed in relation to catecholaminergic systems previously
      reported in avian species and in the mammalian brain.

PMID- 8522652
TI  - Quantitative analysis of synaptogenesis in the inner plexiform layer of macaque
      monkey fovea.
AB  - Synaptogenesis has been tracked by using quantitative electron microscopic
      methods in the inner plexiform layer (IPL) of the developing Macaca monkey fovea
      from fetal day (Fd) 55 to Fd132. Vesicle-containing profiles were classified
      according to whether (1) they contained a ribbon indicating that they originated
      from a bipolar cell, or (2) the profile formed a junction. Group 2 was further
      subdivided by morphological characteristics into (2a) amacrine, (2b) bipolar, or
      (2c) unknown profiles. Ribbon-containing bipolar profiles are clearly
      identifiable at Fd55 when they occur at a density of 0.9/100 microns2. Bipolar
      synapses increase rapidly to 4.7/100 microns2 by Fd88, similar to their density
      at Fd132. Identifiable amacrine profiles forming a junction are rare at Fd55-68.
      By Fd88, amacrine synaptic density has jumped to 6.7/100 microns2 and continues
      to increase to 9.5/100 microns2 at Fd132. These quantitative data strongly
      suggest that, at the Macaca fovea, bipolar synaptogenesis both begins and ends
      before amacrine synaptogenesis. The large number of immature amacrine synaptic
      profiles and densities at Fd132 suggests that amacrine synapses continue to form
      after Fd132. This study confirms that cone-dominated monkey fovea has a different
      sequence of synaptogenesis than the rod-dominated peripheral retina (Nishimura
      and Rakic, [1985] J. Comp. Neurol 241:420-434). The data support the concept that
      synaptic developmental sequence is determined by the type of photoreceptor which
      dominates a particular retinal region or species. Bipolar ribbon synapses are
      observed in the outer half of the IPL at Fd55, are present in the inner IPL at
      Fd60, and then, with increasing age, are found throughout the IPL. This pattern
      strongly suggests that vertical OFF bipolar pathways form earlier than ON
      pathways in the IPL. In contrast, amacrine profiles are found throughout the IPL
      at the youngest ages, with an adult-like banding pattern present by Fd132.

PMID- 8522653
TI  - Tempo of neurogenesis and synaptogenesis in the primate cingulate mesocortex:
      comparison with the neocortex.
AB  - In the neocortex, the onset of the rapid phase (phase 3) of synaptogenesis occurs
      after the end of neurogenesis. However, we still do not know whether or not these
      two developmental events are causally related. The present study compares the
      time-course and tempo of neurogenesis and synaptogenesis in the anterior
      cingulate cortex (area 24 of Brodmann) and in the primary visual cortex (area 17)
      in a series of pre- and postnatal rhesus monkeys. Autoradiographic analysis of
      animals fetally injected with 3H-thymidine showed that all neurons destined for
      area 24 are generated by embryonic day 70, which is 30 days earlier than in area
      17. The rapid phase of synaptogenesis in area 24 starts during the third
      embryonic month and continues at the same rate through the remainder of gestation
      and the first 2 months after birth, as has been seen in neocortical areas
      examined previously. Statistical analysis of the linear portions of the rapid
      phase indicates that, although neurogenesis in area 24 is completed 1 month
      earlier than in area 17, the rapid phase of synaptogenesis occurs 41 days later.
      Moreover, the tempo of synaptic accretion was remarkably similar to that in
      motor, somatosensory, visual, or associational areas. All were grouped within the
      same time window of about 40 days, centered at birth. After the second postnatal
      month, synaptic density in area 24 remains at a high level until sexual maturity.
      This work shows that the rapid phase of synaptogenesis in the cingulate
      mesocortex is not linked temporally to the end of neurogenesis. We suggest that
      it is regulated by the same genetic or humoral factors that control
      synaptogenesis in the phylogenetically newer neocortical areas.

PMID- 8522654
TI  - Assessment of dental student studying strategies.
AB  - This study evaluated the studying strategies of second-year and third-year dental
      students as related to end-quarter exam preparation. Focus groups were convened
      to elicit current student studying strategies that were incorporated into a three
      question survey and administered to second- and third-year students. Strategic
      use of study resources was rank ordered in the first question; course
      characteristics influencing study prioritization were rank ordered in the second
      question; and a third question addressed strategic time management. Overall, both
      second- and third-year students ranked the studying resource "notepool" first,
      although students of high academic standing ranked "texts and syllabi" first.
      Regarding course characteristics, both classes gave high ranking to "instructor
      expectations," "performance on midterm," and "course structure." Second-year
      students rated "performance on midterm" as significantly more important to
      prioritization than did third-year students (p = 0.01, t-test). As to time
      management, a statistically significant number of second-year students (p < 0.01,
      chi-square) ranked "studying for exams mid-quarter" first while third-year
      students (p = 0.05) ranked "studying the week before finals" first. Second- and
      third-year students of high academic standing indicated that they began studying
      at the beginning of the quarter. The data suggest that studying strategies change
      as students progress in school and that students of high and low academic ranking
      differ in the strategies they employ.

PMID- 8522655
TI  - Dental hygienists' information seeking and computer application behavior.
AB  - A questionnaire requesting information on information seeking, critical analysis,
      and computer applications was returned in 1992 by 136 of 197 (69 percent)
      currently licensed dental hygienists residing in Alaska, Delaware, and Idaho. The
      most common sources used for professional development and information retrieval
      were continuing education courses, discussions with colleagues, and journals. The
      respondents' own experience, credibility of the journal, and discussions with
      colleagues were the most frequent methods used to evaluate professional
      information. Many hygienists owned or had access to a computer, yet they rarely
      conducted online database searches to obtain professional information. The
      computer was primarily used to perform business functions rather than for
      clinical applications in these dental hygienists' employment settings. The
      majority of these hygienists were interested in attending related continuing
      education courses and indicated that computer skills should be part of dental
      hygiene curricula.

PMID- 8522656
TI  - Opinions and experiences of dental students and faculty concerning computer
      assisted learning.
AB  - This study assessed the opinions and attitudes of faculty and students concerning
      the use of computer-assisted learning (CAL) at three different dental schools on
      two continents (Manchester, U.K.; Nijmegen, The Netherlands; and Lexington,
      Kentucky, U.S.A.). In each school students and faculty received a questionnaire;
      faculty by internal mail, students at the end of a lecture. Response rates for
      students were 76 percent in Manchester, 64 percent in Nijmegen, and 91 percent in
      Lexington. The respective figures for faculty were: 42 percent, 47 percent, and
      39 percent. In all three schools approximately 50 percent of students had a
      computer at home. Students in Lexington and Manchester seemed to be more advanced
      in the use of computers for self-instructional learning. Students and faculty in
      Lexington had more experience with interactive multimedia than did those in
      Manchester and Nijmegen. In general, Lexington students were somewhat more
      familiar with computers and CAL than Manchester students, with Nijmegen showing
      the lowest percentages. Few CAL programs were available at any school, with small
      numbers of dental students having been exposed to programs involving animation
      (vision, sound). The majority of students are of the opinion that the use of
      computers for learning is not impersonal, nor difficult, but challenging and
      motivating. There is good agreement that if a program is to be bought or
      developed, it should be a combination of text, images, and sound. It is
      postulated that concerted action by dental schools is required to realize the
      potential of CAL in dental education, and that international organizations should
      give consideration to coordinating this action.

PMID- 8522657
TI  - Program assessment practices in dental hygiene education.
AB  - A survey asked U.S. dental hygiene program directors to describe their assessment
      programs and satisfaction with these programs. A 65 percent response rate
      (138/212) resulted. The directors were less than satisfied with their assessment
      practices and how they use their assessment data. The majority use alumni (78
      percent) and employer (61 percent) surveys and curriculum evaluations by students
      (57 percent). Fewer use patient satisfaction surveys (40 percent) and exit
      interviews (33 percent). Only 35 percent of the programs formally validate any
      instruments. They share the results with faculty (92 percent) but not students
      (42 percent) and alumni (25 percent). They use the data for curriculum revision
      (84 percent) but not for adding assessment measures (26 percent), remediation of
      students (25 percent), or gaining resources for the program (22 percent). Dental
      hygiene education needs a more comprehensive assessment model that is clearly
      linked to improvement.

PMID- 8522658
TI  - An application of outcomes assessment in dental education.
AB  - The outcomes assessment process developed by the New Jersey Dental School is
      described. The paper identifies required resources, presents selected outcome
      measures, reviews strengths and weaknesses of the process, and reports how
      ongoing assessment activities have evolved. Documentation produced as part of the
      outcomes assessment process is also described, allowing health professions
      schools to implement a similar process.

PMID- 8522659
TI  - Dental students' choice of learning resources.

PMID- 8522660
TI  - Predicting dental school clinic fees.

PMID- 8522661
TI  - Combining dental training with medical training.

PMID- 8522662
TI  - Employing teamwork and hard work for excellence in dentistry.

PMID- 8522663
TI  - Heatstroke: a new look at an ancient disease.

PMID- 8522664
TI  - Scorpion envenomation.

PMID- 8522665
TI  - Assessment of left ventricular function in severe scorpion envenomation: combined
      hemodynamic and echo-Doppler study.
AB  - OBJECTIVE: To assess left ventricular function in patients presenting with
      pulmonary edema following scorpion envenomation. DESIGN: Cohort study. SETTING:
      Medical intensive care unit of a teaching hospital. PATIENTS: Nine consecutive
      adult patients stung by Androctonus australis and presenting with pulmonary edema
      entered the study. Fourteen normal volunteers comprised the control group.
      INTERVENTIONS: Upon admission, all patients had right heart catheterization and,
      within the first 8 h, a Doppler echocardiographic study. Results of Doppler
      echocardiographic studies were compared to those of controls. MEASUREMENTS AND
      RESULTS: Usual hemodynamic information (heart and vascular pressures, derived
      data and tissue oxygenation parameters), left ventricular dimensions and
      indicators of systolic function, and Doppler-derived parameters of left
      ventricular filling and diastolic function were obtained upon admission. Serial
      echocardiographic measurements were repeated daily until full clinical recovery
      (eight patients) or death (one patient). All patients had a hemodynamic profile
      of acute congestive heart failure (mean PAOP = 24 +/- 2 mmHg; mean SVI = 22 +/- 7
      ml/m2; mean CI = 2.5 +/- 0.5 l/min/m2). However, SVR were not increased (mean =
      22 +/- 3 U/m2). Left ventricle was hypokinetic in all patients with transient
      mitral regurgitation present in five patients. Left ventricular systolic function
      was markedly depressed (FS = 12 +/- 6%; EF = 26 +/- 12%). An associated diastolic
      dysfunction is suggested by Doppler records of mitral inflow. Left ventricular
      systolic function evolved toward normalization within 6 +/- 2 days preceded by
      full clinical recovery. CONCLUSIONS: These data suggest that pulmonary edema in
      scorpion envenomation is of hemodynamic origin and is related to a severe and
      prominent impairment of left ventricular systolic function.

PMID- 8522666
TI  - Increased neutrophil elastase release in patients with cardiopulmonary arrest:
      role of elastase inhibitor.
AB  - OBJECTIVE: To determine the changes in neutrophil elastase levels in patients
      with cardiac arrest occurring outside the hospital and to evaluate the effects of
      urinastatin on these changes and on the clinical outcomes of the patients.
      DESIGN: Prospective study. SETTING: The Emergency Department and a general ICU in
      the tertiary care city hospital. PATIENTS: Of the 40 patients who had an out-of
      hospital cardiac arrest, 38 of the cases were randomized into 2 groups, with 2
      cases being excluded because of contradiction to protocol. The control and
      urinastatin groups consisted of 20 and 18 patients, respectively. INTERVENTIONS:
      Control patients were treated by standard cardiopulmonary resuscitation (CPR)
      procedures. Patients in the urinastatin group were administered a 100,000 U dose
      of urinastatin immediately after arrival at the Emergency Department and three
      100,000 U doses at 8 h intervals, within the first 24 h after resuscitation.
      MEASUREMENTS AND MAIN RESULTS: At the time of arrival at the emergency room
      (before administration of urinastatin), and at 30 min, 60 min, and 24 h after,
      the plasma levels of neutrophil elastase and blood gas levels were determined.
      Concerning the baseline characteristics of patients, causes of cardiac arrest,
      time duration of pre-hospital care and treatments given during CPR, there was no
      difference detected between the control and urinastatin groups. In addition, the
      pH and PaO2 values showed no differences. Neutrophil elastase values had already
      increased by the time of arrival and continued to do so until 60 min; at 24 h
      after admission, markedly higher values were obtained. These values were
      significantly higher in the non-resuscitated cases than in the resuscitated ones.
      Administration of urinastatin significantly suppressed this increase at 24 h, but
      did not improve the clinical outcomes, including resuscitation rate and survival
      rate. CONCLUSIONS: Accompanying cardiopulmonary arrest and resuscitation,
      neutrophils are activated and elastase is released. Elevated elastase level is
      associated with poorer prognosis. Urinastatin can suppress the release of
      elastase, when utilized at the dose described in this study, did not improve the
      clinical outcomes of patients who had suffered an out-of-hospital cardiac arrest.

PMID- 8522667
TI  - Isoniazid overdose: four case reports and review of the literature.
AB  - OBJECTIVES: To review the pathophysiology, presentation and treatment of
      isoniazid (INH) intoxication. DATA SOURCES: Human, animal and modeling studies
      published since 1940 identified through MEDLINE and a review of the
      bibliographies of relevant articles. STUDY SELECTION AND DATA EXTRACTION: The
      studies identified were reviewed with emphasis on the most recent. Earlier
      studies were selected for their historical value and relevance to the clinical
      setting. DATA SYNTHESIS: Isoniazid overdose is a potentially fatal intoxication.
      The incidence of tuberculosis has recently increased in the United States and
      therefore the frequency of INH overdose may also increase. Patients with INH
      overdose may present with nausea, vomiting, ataxia, symptoms reminiscent of
      atropine intoxication, coma and grand mal seizures. Lactic acidosis is revealed
      by laboratory evaluation. Treatment requires admission to the ICU for ventilatory
      support, and management of seizures and acid-base abnormalities. Pyridoxine, in a
      dose equivalent to the amount of INH ingested, is the only effective antidote.
      CONCLUSIONS: INH overdose should be suspected in any patient presenting with
      seizures and metabolic acidosis. Prognosis is good when treatment is instituted
      early.

PMID- 8522668
TI  - Thrombomodulin in intensive care patients.
AB  - OBJECTIVE: Changes of endothelial-related coagulation was studied in intensive
      care patients. DESIGN: Descriptive, prospective. SETTING: Clinical investigation,
      intensive care unit of an university hospital. PATIENTS: 40 consecutive
      critically ill patients with severe trauma (n = 20) or postoperative
      complications (n = 20) were studied. 14 patients suffered from sepsis, 12
      patients suffered from acute renal failure. INTERVENTIONS: 12 patients with acute
      renal failure were continuously hemofiltrated. All patients were on continuous
      sedation (fentanyl and midazolam) and mechanical ventilation. MEASUREMENTS: In
      addition to standard coagulation variables, thrombomodulin (TM), protein C and
      protein S as well as thrombin/antithrombin III (TAT) plasma concentrations were
      measured from arterial blood samples using enzyme-linked immuno-sorbent assays
      (ELISA). Measurements were carried out on the day of admission (trauma patients)
      or on the day of diagnosis of sepsis and during the next 4 days. MAIN RESULTS:
      Throughout the entire investigation period, TM plasma concentrations in patients
      with sepsis (baseline: 90 +/- 25 micrograms/l, 4th day: 152 +/- 28 micrograms/l)
      were significantly higher than in non-septic patients (baseline: 60 +/- 29
      micrograms/l, 4th day: 42 +/- 15 micrograms/l). 15 of the 40 patients died within
      or after the end of the investigation period. TM plasma concentrations of
      survivors were lower (maximum: 63 +/- 18 micrograms/l) than in the non-survivors
      (maximum: 159 +/- 22 micrograms/l) (p < 0.05). Hemofiltered patients showed
      higher TM plasma levels, which further increased during the hemofiltration
      procedure. Protein C and (free) protein S were without significant group
      differences. TAT plasma levels were elevated above normal in all patients (no
      group differences). CONCLUSIONS: Besides plasmatic and platelet-related
      coagulation, endothelium-associated coagulation appears to be also important for
      maintenance of hemostasis. TM plasma concentrations were elevated in all our
      critically ill patients, particularly when sepsis was evident. This appears to be
      most likely due to endothelial membrane damage with increased release of membrane
      bound TM into the circulating blood in these patients. The importance of the
      elevated plasma levels of circulating soluble TM on hemostasis in these patients
      is an ongoing debate and warrants further studies.

PMID- 8522669
TI  - Enalaprilat controls postoperative hypertension while maintaining cardiac
      function and systemic oxygenation after neurosurgery.
AB  - OBJECTIVE: The efficacy of intravenous enalaprilat in lowering postoperative
      hypertension. DESIGN: Prospective, randomized, controlled, single blind trial.
      SETTING: Surgical ICT in a university hospital (tertiary care center). PATIENTS:
      18 neurosurgical patients subjected to the extirpation of a supratentorial
      intracerebral tumour were studied after detection of postoperative hypertension.
      This was defined as a constant elevation of systolic arterial pressure over 160
      mmHg or diastolic arterial pressure over 95 mmHg. INTERVENTIONS: Enalaprilat
      0.015 mg kg-1 was injected within 5 min to 9 patients. MEASUREMENTS AND RESULTS:
      Central haemodynamics and systemic oxygenation were assessed at baseline before
      enalaprilat injection, and repeatedly during four hours after the injection. The
      statistical analysis was performed with analysis of variance for repeated
      measurements. As compared to control patients, the blood pressure lowering effect
      of enalaprilat became evident within 15 min and lasted for over four hours (p =
      0.008). It was mainly due to the reduced systemic vascular resistance.
      Enalaprilat also induced a small decline in myocardial perfusion pressure.
      Cardiac performance, preload, heart rate and systemic oxygenation were not
      affected by enalaprilat. CONCLUSIONS: We found intravenous enalaprilat effective
      and safe in lowering postoperative hypertension following neurosurgery as
      assessed by it's effects on central haemodynamics and systemic oxygenation.

PMID- 8522670
TI  - Reliability in diagnosis of brain death.
AB  - OBJECTIVE: To compare some of the confirmatory investigations of brain death with
      clinical criteria in order to achieve the most sensitive and accurate diagnosis
      of brain death. DESIGN: All patients with isolated brain lesions and Glasgow Coma
      Scale (GCS) = 3 were subjected to neurological examination after ruling out
      hypothermia, metabolic disorders and drug intoxications and diagnosed as
      clinically brain-dead when the brainstem reflexes were absent and the apnea test
      positive. PATIENTS: 15 patients with clinical diagnosis of brain death entered
      this study. MEASUREMENTS AND RESULTS: The patients were submitted to the
      following investigations: electroencephalogram (EEG), transcranial Doppler (TCD)
      of the middle cerebral arteries (MCA), cerebral blood flow measurements with the
      i.v. Xe-133 method (CBF) and selective cerebral angiography (CA). EEG was
      isoelectric in 8 patients while the remaining 7 patients showed persistence of
      electrical activity. TCD was compatible with intracranial circulatory arrest in
      18 MCA districts, compatible with normal flow in 2 and undetectable in 10 out of
      30 districts insonated. In CBF examinations, however, all the patients showed a
      characteristic "plateau" of the desaturation curves lasting through the whole
      investigation and suggestive of absent cortical flow. CA showed circulatory
      arrest in both carotid and vertebral arteries. CONCLUSIONS: Our study suggests
      that cerebral angiography and CBF studies are the most reliable investigations
      whereas the role of EEG and TCD remains to be determined because of the presence
      of false negatives and positives.

PMID- 8522671
TI  - The repeated measurement of vital capacity is a poor predictor of the need for
      mechanical ventilation in myasthenia gravis.
AB  - OBJECTIVE: Testing the hypothesis that, in myasthenia gravis (MG), repeated
      measurements of vital capacity (VC) and various parameters derived from this
      measurement [median or lowest value of measured VCs during hospitalization, VC
      values < 20 ml/kg body weight (BW) or < 13 ml/kg BW, or an index assessing the
      variability of VC values during the whole ICU stay] could predict the need for
      intubation and mechanical ventilation (MV), as has been shown in other
      neuromuscular diseases with respiratory failure. DESIGN: Retrospective study with
      medical chart revision of all the patients with MG and respiratory failure
      admitted to our intensive care unit between 1985 and 1993. SETTING: Medical
      intensive care unit (15 beds) of a university hospital. PATIENTS AND METHODS:
      Five patients suffering from ten episodes of acute respiratory failure due to
      their decompensated MG. Repeated measurements of arterial blood gases and VC by
      trained respiratory therapists, at least every 4 h. RESULTS: There was no
      difference in any of these parameters between patients eventually requiring MV
      (four episodes) and those in whom mechanical ventilation was not necessary (six
      episodes). CONCLUSIONS: VC repeated measurements is a poor predictor of the need
      for further MV in MG patients. This can probably be ascribed to the erratic
      nature of MG, a disease whose course is largely influenced by many parameters
      (infection, treatment modifications, initiation of corticosteroid therapy,
      stress, psychological factors, etc.). Early admissions to the ICU of MG patients
      with respiratory dysfunction is thus recommended.

PMID- 8522672
TI  - Dynamics of skin blood flow in human sepsis.
AB  - OBJECTIVE: The study was undertaken to determine if sepsis alters the pattern of
      vasomotion and reactive hyperaemia in the skin. DESIGN: This was a prospective,
      observational study. SETTING: The study was performed in the medical and surgical
      intensive care units of a tertiary referral hospital. PATIENTS AND PARTICIPANTS:
      11 patients with sepsis (using Bone's criteria [1]), were compared with 19
      patients recovering from coronary artery bypass grafting who were used as non
      septic controls. Nineteen normal volunteers were also studied. MEASUREMENTS AND
      RESULTS: Skin blood flow was measured on the forearm using laser Doppler
      flowmetry at rest and after 2 min arterial occlusion with a tourniquet. The
      resting blood signal was analyzed by calculating the mean skin blood flow, the
      power of the skin blood flow signal (variance) and the power spectrum. The rate
      of recovery after arterial occlusion was determined by calculating the peak
      increase in skin blood flow and the time constant of the decay of skin hyperaemia
      back to baseline flow. Patients with sepsis had a mean skin blood flow of 6.24
      (3.48) ml min-1 per 100 g tissue compared with 4.35 (1.41) ml min-1 per 100 g
      tissue for the patients after coronary artery bypass grafting (p < 0.05). The
      septic patients also showed a marked increase in the fraction of total power in
      the 0.1-0.15 Hz frequency band (0.19 (0.17) versus 0.068 (0.033), p < 0.05), a
      decreased peak hyperaemic response (40 (23)% increase in flow above baseline
      after cuff release versus 147 (19)%) and a prolonged time constant for recovery
      from hyperaemia (22.8 (12.7) versus 11.7 (8.5) seconds, p < 0.05). These results
      imply an increased local rather than central control of skin blood flow.
      CONCLUSION: The laser Doppler flowmeter allows local rather than global
      haemodynamics to be studied. Abnormalities of skin blood flow control are found
      in sepsis, and this technique may prove useful to monitor the effects of
      treatment, especially if the use of laser Doppler flowmetry can be extended to
      other organs at risk of damage during sepsis such as gastro-intestinal mucosa.

PMID- 8522673
TI  - Inhaled nitric oxide for hemodynamic support after postpneumonectomy ARDS.
AB  - Inhaled nitric oxide (NO) has been reported to promote selective pulmonary
      vasodilation and better arterial oxygenation in cases of adult respiratory
      distress syndrome (ARDS) with pulmonary hypertension (PHT). However, the clinical
      relevance of these changes and their effects on outcome remain to be proven,
      since long-term inhalation carries a potential risk of toxicity. We used NO to
      treat a patient who developed postpneumonectomy ARDS with severe PHT and right
      ventricular failure. NO resulted in better oxygenation and markedly improved
      hemodynamic status. As the underlying disease progressively worsened the patient
      became fully dependent on NO for hemodynamic support, and he died after 24 days
      of effective supportive therapy with inhaled NO.

PMID- 8522674
TI  - Magnetic resonance imaging of cerebral fat embolism: a case report.
AB  - Fat embolism syndrome (FES) is one of the most important causes of morbidity and
      mortality following multiple fractures. Neurological involvement (cerebral fat
      embolism) has been reported frequently. A case of cerebral fat embolism is
      reported. While CT scan revealed no abnormalities, MRI, performed in this patient
      8 days after trauma, showed relative low-intensity areas on T1-weighted images
      and high intensity areas on T2-weighted images involving cerebral white matter,
      corpus callosum and basal ganglia. MRI follow-up (1 and 3 months post-trauma)
      showed nearly complete resolution of the abnormal signal. MRI seems to be a
      useful diagnostic tool for detecting and quantifying lesions in fat embolism
      syndrome.

PMID- 8522675
TI  - Flow-triggering reduces inspiratory effort during weaning from mechanical
      ventilation.
AB  - OBJECTIVE: To investigate whether a new flow-triggered (FT) system can reduce the
      patient's inspiratory effort compared to a traditional pressure-triggered (PT)
      system during weaning from mechanical ventilation. DESIGN: Prospective study.
      SETTING: Intensive care unit of a General Hospital. PATIENTS AND PARTICIPANTS: 10
      mechanically ventilated patients, without chronic airway disease, ready to wean.
      MEASUREMENTS: Minute ventilation, breathing pattern, lung mechanics, inspiratory
      work of breathing (WI) and pressure time product (PTP) of Ppl were obtained in
      two conditions: 1) unsupported spontaneous breathing through the ventilator
      circuit (SB); 2) spontaneous breathing with continuous positive airway pressure
      set at 5 cmH2O (CPAP). Two triggering systems, namely PT and FT, were used in
      each condition. RESULTS: Though there was no change in breathing pattern, minute
      ventilation, and lung mechanics, the magnitude of the inspiratory effort
      decreased significantly with FT compared to PT in both instances. The added
      resistance (total flow resistance minus pulmonary resistance) decreased by 37% on
      average when FT replaced PT. PTP decreased, on average, 27% and 15% during SB and
      CPAP, respectively, with FT compared to PT (p < 0.05). A similar significant
      decrease was observed in WI. CONCLUSION: The new FT system, i.e. flow-by system,
      reduces the unintentional ventilatory workload upon the patients' inspiratory
      muscles compared to traditional PT system during weaning from mechanical
      ventilation.

PMID- 8522676
TI  - Safety of tracheotomy in neutropenic patients: a retrospective study of 26
      consecutive cases.
AB  - OBJECTIVE: To evaluate the safety of tracheotomy in neutropenic ventilated cancer
      patients, in terms of infectious and haemorrhagic complications. DESIGN:
      Retrospective study. SETTING: A medical-surgical intensive care unit in a Cancer
      hospital. PATIENTS AND PARTICIPANTS: 26 consecutive patients undergoing a
      tracheotomy in neutropenic period, from 1987 to 1990. INTERVENTIONS: Tracheotomy,
      performed at the bedside or in operating room. MEASUREMENTS AND RESULTS: In all
      neutropenic patients undergoing a tracheotomy, the characteristics and duration
      of both neutropenia and mechanical ventilation have been recorded. Stomal
      bleeding and infection, and infectious pneumonias and alveolar haemorrhage have
      been carefully reviewed. Platelets were transfused in 23 of the 26 patients at
      the time of the procedure; no local haemorrhage was observed. Neither stomal nor
      pulmonary infections secondary to tracheotomy were noted. No respiratory
      worsening was attributable to the tracheotomy. Nineteen patients (73%) died in
      ICU, without direct link between tracheotomy and death. CONCLUSIONS: These
      findings suggest that a tracheotomy can be safely performed in neutropenic
      patients requiring mechanical ventilation.

PMID- 8522677
TI  - The thermodilution method for the clinical assessment of cardiac output.

PMID- 8522678
TI  - Importance of the inhaler mouthpiece cover.

PMID- 8522679
TI  - Amniotic fluid embolism: another case with non-cardiogenic pulmonary edema.

PMID- 8522680
TI  - Elimination of liposomal amphotericin by hemodiafiltration.

PMID- 8522681
TI  - Restenosis, reocclusion and adverse cardiovascular events after successful
      balloon angioplasty of occluded versus nonoccluded coronary arteries. Results
      from the Multicenter American Research Trial With Cilazapril After Angioplasty to
      Prevent Transluminal Coronary Obstruction and Restenosis (MARCATOR).
AB  - OBJECTIVES: This study sought to compare the frequency of restenosis, reocclusion
      and adverse cardiovascular events after angioplasty of occluded versus
      nonoccluded coronary arteries. BACKGROUND: Angioplasty of chronically occluded
      coronary arteries is believed to be associated with a higher frequency of
      restenosis and reocclusion than angioplasty of subtotal stenoses. Whether this
      leads to adverse cardiovascular events is unknown. METHODS: The Multicenter
      American Research Trial With Cilazapril After Angioplasty to Prevent Restenosis
      (MARCATOR) was a placebo-controlled trial with angiographic follow-up to
      determine the effect of the angiotensin-converting enzyme inhibitor cilazapril on
      the frequency of restenosis. In this trial, restenosis was defined as 1)
      angiographic reduction of minimal lumen diameter > or = 0.72 mm between
      angioplasty and the follow-up visit; and 2) > 50% diameter stenosis on the follow
      up angiogram. We identified 139 patients with successful angioplasty of a
      coronary occlusion (Group 1) and compared the frequency of restenosis,
      reocclusion and adverse cardiovascular events with that in 1,295 patients with
      successful angioplasty of a subtotal stenosis (Group 2). RESULTS: Restenosis
      occurred in 36 patients with occluded arteries (29%) versus 264 with nonoccluded
      arteries (23%, p = 0.177) by definition 1 and in 62 patients with occluded
      arteries (49%) versus 478 with nonoccluded arteries (42%, p = 0.119) by
      definition 2. Occlusion was present in 24 Group 1 patients (19%) compared with 74
      Group 2 patients (7%) (p < 0.001). During the 6 month follow-up period, two Group
      1 patients (1.4%) and six Group 2 patients (0.5%) died; no Group 1 patients and
      10 Group 2 patients (0.8%) developed severe congestive heart failure; nonfatal
      myocardial infarction occurred in 4 Group 1 patients (2.9%) and 31 Group 2
      patients (2.4%); repeat coronary angioplasty or bypass surgery was performed in
      29 Group 1 patients (21%) and 232 Group 2 patients (18%); and angina was present
      in 18 Group 1 and 163 Group 2 patients (13% for both). Eighty-six Group 1
      patients (62%) and 853 Group 2 patients (66%) remained free of these adverse
      events during the 6-month follow-up period (p = 0.513). CONCLUSIONS: The
      frequency of restenosis was slightly but not significantly greater after
      successful angioplasty of an occluded artery than after angioplasty of a subtotal
      stenosis. Although reocclusion was more frequent, occurring in 19% of patients,
      the net clinical benefit of angioplasty in such patients was similar to that in
      patients with subtotal stenoses over the 6-month follow-up period.

PMID- 8522682
TI  - Diagnosis of ascending aortic dissection by transesophageal echocardiography:
      utility of M-mode in recognizing artifacts.
AB  - OBJECTIVES: This study sought to assess the reliability of biplanar
      transesophageal echocardiography in the diagnosis of ascending aortic dissection
      and to test the utility of M-mode information in the differential diagnosis of
      ascending aortic ultrasound artifacts and intimal flap images. BACKGROUND:
      Transesophageal echocardiography is a useful technique in the diagnosis of aortic
      dissection. However, ultrasound artifacts in the ascending aorta are an important
      limitation. METHODS: Transesophageal echocardiography was performed in 132
      consecutive patients with clinically suspected aortic dissection. Two-dimensional
      and M-mode echocardiography and color Doppler were used to diagnose intimal flap
      and artifact images. Diagnoses were validated either anatomically or with
      reference techniques. RESULTS: The sensitivity and specificity of transesophageal
      echocardiography in the diagnosis of ascending aortic dissection were 96.8% and
      100%, respectively. Ninety-three artifacts were observed in 56 (55%) of 101
      patients without ascending aortic dissection. Two-dimensional echocardiography
      easily identified 74 artifacts (80%). Color Doppler showed no ascending flow
      abnormalities in 71% of artifact images. M-mode echocardiography showed three
      location and mobility artifact patterns related to the posterior wall of the
      aorta or the right pulmonary artery. In contrast, intimal flap movement showed no
      relation to the aortic wall movement in 25 cases (83%). Blind analysis of
      transesophageal echocardiographic study tapes underlined the utility of M-mode in
      the differential diagnosis. Ranges of sensitivity, specificity and positive
      predictive value (established by including doubtful results as either positive or
      negative) improved from 87.1-93.5% to 93.5-96.8%, from 85.1-94.1% to 99-100% and
      from 65.9-81.8% to 96.8-100%, respectively, with the inclusion of M-mode data.
      CONCLUSIONS: Biplanar transesophageal echocardiography permits reliable diagnosis
      of ascending aortic dissection. Ultrasound artifacts are common, but assessment
      of the location and mobility of intraluminal images by M-mode echocardiography
      definitely improves diagnostic accuracy.

PMID- 8522683
TI  - Differentiation of constrictive pericarditis from restrictive cardiomyopathy:
      assessment of left ventricular diastolic velocities in longitudinal axis by
      Doppler tissue imaging.
AB  - OBJECTIVES: We sought to determine the utility of left ventricular expansion
      velocities in differentiating constrictive pericarditis from restrictive
      cardiomyopathy. BACKGROUND: Several studies have shown that left ventricular
      diastolic expansion is influenced by the elastic recoil forces of the myocardium.
      These forces are affected by intrinsic myocardial disease but should be preserved
      when diastole is impaired as a result of extrinsic causes. METHODS: Using Doppler
      tissue imaging, we measured peak early velocity of longitudinal axis expansion
      (Ea) in 8 patients with constrictive pericarditis, 7 patients with restriction
      and 15 normal volunteers. Transmitral early (E) and late (A) Doppler flow
      velocities, left ventricular systolic and diastolic volumes, ejection fraction
      and mitral annular M-mode displacement were also compared between the groups.
      RESULTS: The Ea value was significantly higher in normal subjects (14.5 +/- 4.7
      cm/s [mean +/- SD]) and in patients with constriction (14.8 +/- 4.8 cm/s) than in
      those with restriction (5.1 +/- 1.4 cm/s, p < 0.001 constriction vs.
      restriction). There was weak correlation between Ea and the extent of annular
      displacement (r = 0.55, p = 0.004) and the E/A ratio (r = 0.44, p = 0.03). There
      was no correlation between Ea and E (r = 0.33, p = 0.07) or ejection fraction (r
      = 0.21, p = 0.26). By multivariate analysis, Ea was the best variable for
      differentiating constriction from restriction. CONCLUSIONS: Our study indicates
      that longitudinal axis expansion velocities are markedly reduced in patients with
      restrictive cardiomyopathy. The poor correlation found with transvalvular flow
      velocities suggests that Ea may be relatively preload independent. The
      measurement of longitudinal axis expansion velocities provides a clinically
      useful distinction between constrictive pericarditis and restrictive
      cardiomyopathy and may prove to be valuable in the study of diastolic function.

PMID- 8522684
TI  - Epicardial coronary arteries are not adequately sized in hypertensive patients.
AB  - OBJECTIVES: This study sought to compare coronary artery dimensions in
      hypertensive patients and normal subjects. BACKGROUND: Myocardial oxygen demand
      at rest and corresponding coronary blood flow are the main determinants of large
      coronary artery dimensions in humans. Coronary diameters are increased in aortic
      valve disease. METHODS: Left main, proximal and distal left anterior descending
      and proximal circumflex coronary artery diameters were measured by quantitative
      angiography in 10 control subjects (group 1) and 26 untreated hypertensive
      patients, 12 without (group 2a) and 14 with (group 2b) left ventricular
      hypertrophy. All patients had normal cholesterol levels and angiographically
      normal coronary arteries. Measurements were made at baseline and after 2 mg of
      intracoronary isosorbide dinitrate to obtain maximal dimensions of vessels.
      Coronary flow velocity was measured in the distal left anterior descending
      coronary artery by Doppler ultrasound. RESULTS: Despite a higher rate-pressure
      product in hypertensive patients, all segment diameters were slightly but not
      significantly higher at baseline in group 2b than in groups 1 and 2a. Diameters
      were similar in the three groups after isosorbide dinitrate. Conversely, coronary
      flow velocity was significantly higher in hypertensive patients than in group 1
      either at baseline (10.4 +/- 2.2 [mean +/- SD] cm/s [group 2a] and 12.8 +/- 2.4
      cm/s [group 2b] vs. 6.5 +/- 2.0 cm/s [group 1], all p < 0.001) or after
      isosorbide dinitrate (6.8 +/- 2.8 cm/s [group 2a] and 7.8 +/- 2.1 cm/s [group 2b]
      vs. 3.7 +/- 0.8 cm/s [group 1], p < 0.01 and p < 0.001, respectively).
      CONCLUSIONS: Despite an elevated myocardial oxygen demand, maximal dimensions of
      large coronary arteries are not increased in hypertensive patients, resulting in
      an elevated coronary flow velocity that may increase longitudinal shear stress at
      the endothelial surface. This elevated flow velocity might be an important
      determinant in the pathogenesis of atherosclerosis in hypertensive patients.

PMID- 8522685
TI  - Electrocardiographic identification of left ventricular hypertrophy: test
      performance in relation to definition of hypertrophy and presence of obesity.
AB  - OBJECTIVES: This study sought to assess a test performance of the
      electrocardiogram (ECG) in relation to 1) varying definitions of left ventricular
      hypertrophy based on different methods of adjusting left ventricular mass for
      body size, and 2) the presence or absence of obesity. BACKGROUND: Although left
      ventricular mass is most commonly indexed for body surface area or height when
      defining left ventricular hypertrophy, recent work suggests that normalization
      for height to the power of 2.7 (height2.7) may decrease variability among normal
      subjects and correctly identify the impact of obesity on hypertrophy. METHODS:
      The product of Cornell voltage and QRS duration (Cornell product) and Framingham
      adjusted Cornell voltage were determined from 12-lead ECGs in 212 patients. Left
      ventricular hypertrophy was defined on the basis of left ventricular mass indexed
      to body surface area, height and height2.7. RESULTS: Using partitions with
      matched specificity of 95%, the sensitivity of ECG criteria varied with the
      definition of hypertrophy, ranging from 39% to 52% for the Cornell product and
      from 24% to 33% for adjusted Cornell voltage. When left ventricular mass was
      indexed to body surface area or to height2.7, the 52% and 39% sensitivities of
      the Cornell product were significantly greater than the 24% (p < 0.001) and 29%
      (p < 0.05) sensitivities of adjusted Cornell voltage, with a similar trend when
      left ventricular mass was indexed to height (43% vs. 33%, p = 0.10). Comparison
      of receiver operating characteristic curves confirmed the superior overall
      performance of the Cornell product relative to adjusted Cornell voltage for
      hypertrophy defined by body surface area and height2.7 and demonstrated greater
      reproducibility of overall performance, as measured by the coefficient of
      variability, for the Cornell product (1.7%) than for adjusted Cornell voltage
      (5.8%). Sensitivity of adjusted Cornell voltage was significantly greater in
      obese than in nonobese subjects (50% to 59% vs. 18% to 24%, p < 0.01), but the
      Cornell product had only minimally higher sensitivity in nonobese than in obese
      subjects (40% to 54% vs. 32% to 44%, p = NS). CONCLUSIONS: The ability of ECG
      criteria to detect left ventricular hypertrophy differs depending on the method
      of indexing left ventricular mass for body size and with the presence or absence
      of obesity. Further, the Cornell product provides the best combination of overall
      accuracy and low variability of performance between definitions of hypertrophy.
      These findings have important implications for the clinical and epidemiologic use
      of 12-lead ECG criteria for the detection of left ventricular hypertrophy.

PMID- 8522686
TI  - Prognostic value of dobutamine echocardiography in patients with left ventricular
      dysfunction.
AB  - OBJECTIVES: This study sought to establish the prognostic implications of
      ischemic and viable myocardium identified by dobutamine echocardiography in
      patients with left ventricular dysfunction. BACKGROUND: Recent studies have
      suggested that in patients with viable myocardium identified by positron emission
      tomography, medical treatment is associated with recurrent cardiac events.
      Dobutamine echocardiography has been used to identify viable myocardium in
      patients with left ventricular dysfunction, but the prognostic significance of
      this test is undefined. METHODS: One hundred thirty-six consecutive patients
      (mean [+/- SD] age 67 +/- 7.9 years; 104 men) with moderate or severe left
      ventricular dysfunction (left ventricular ejection fraction 30 +/- 5%) undergoing
      dobutamine echocardiography were included in the study. Dobutamine was
      administered using a standard incremental protocol (5 to 40 micrograms/kg body
      weight per min intravenously in 3-min stages) with additional atropine (1 mg
      intravenously) as required. Standard body weight echocardiographic views were
      digitized on-line and compared using a side-by-side display. Viable myocardium
      was identified by enhancement of regional function at low dose (< 10 micrograms);
      scar was diagnosed by akinesia at rest or dyskinesia without change and ischemia
      as new or worsening dysfunction. One hundred thirty patients (95%) were followed
      up for 16 +/- 8 months after the original study for major cardiac events (cardiac
      death, myocardial infarction or severe unstable angina requiring late myocardial
      revascularization). RESULTS: No significant complications occurred during
      dobutamine echocardiography. Viable myocardium was detected in 26 patients (19%),
      ischemia in 23 (17%), both viability and ischemia in 13 (10%) and scar in 74
      (54%). Of 108 patients treated medically, 46 had viable or ischemic myocardium,
      and 62 had scar only. There were no significant differences in age or other
      clinical characteristics, stress response, left ventricular dimensions and
      ejection fraction between the two groups. Cardiac events occurred in 26 medically
      treated patients (24%): 18 died of cardiac-related causes; 4 had a nonfatal
      myocardial infarction; and 4 had late revascularization because of unstable
      angina. The event rate was greater in patients with viable or ischemic myocardium
      than those with scar (43% vs. 8%, p = 0.01 by log-rank test). In a Cox regression
      model, the presence of viable or ischemic myocardium was found to predict
      subsequent events (relative risk 3.51, p = 0.02) independently of ejection
      fraction and age. CONCLUSIONS: Viable or ischemic myocardium detected at
      dobutamine echocardiography in patients with left ventricular dysfunction is
      associated with an adverse prognosis, independent of age and ejection fraction.

PMID- 8522687
TI  - Relation of systemic and local muscle exercise capacity to skeletal muscle
      characteristics in men with congestive heart failure.
AB  - OBJECTIVES: The present study was undertaken to further characterize changes in
      skeletal muscle morphology and histochemistry in congestive heart failure and to
      determine the relation of these changes to abnormalities of systemic and local
      muscle exercise capacity. BACKGROUND: Abnormalities of skeletal muscle appear to
      play a role in the limitation of exercise capacity in congestive heart failure,
      but information on the changes in muscle morphology and biochemistry and their
      relation to alterations in muscle function is limited. METHODS: Eighteen men with
      predominantly mild to moderate congestive heart failure (mean +/- SEM New York
      Heart Association functional class 2.6 +/- 0.2, ejection fraction 24 +/- 2%) and
      eight age- and gender-matched sedentary control subjects underwent measurements
      of peak systemic oxygen consumption (VO2) during cycle ergometry, resistance to
      fatigue of the quadriceps femoris muscle group and biopsy of the vastus lateralis
      muscle. RESULTS: Peak VO2 and resistance to fatigue were lower in the patients
      with heart failure than in control subjects (15.7 +/- 1.2 vs. 25.1 +/- 1.5 ml/min
      kg and 63 +/- 2% vs. 85 +/- 3%, respectively, both p < 0.001). Patients had a
      lower proportion of slow twitch, type I fibers than did control subjects (36 +/-
      3% vs. 46 +/- 5%, p = 0.048) and a higher proportion of fast twitch, type IIab
      fibers (18 +/- 3% vs. 7 +/- 2%, p = 0.004). Fiber cross-sectional area was
      smaller, and single-fiber succinate dehydrogenase activity, a mitochondrial
      oxidative marker, was lower in patients (both p < or = 0.034). Likewise, the
      ratio of average fast twitch to slow twitch fiber cross-sectional area was lower
      in patients (0.780 +/- 0.06 vs. 1.05 +/- 0.08, p = 0.019). Peak VO2 was strongly
      related to integrated succinate dehydrogenase activity in patients (r = 0.896, p
      = 0.001). Peak VO2, resistance to fatigue and strength also correlated
      significantly with several measures of fiber size, especially of fast twitch
      fibers, in patients. None of the skeletal muscle characteristics examined
      correlated with exercise capacity in control subjects. CONCLUSIONS: These results
      indicate that congestive heart failure is associated with changes in the
      characteristics of skeletal muscle and local as well as systemic exercise
      performance. There are fewer slow twitch fibers, smaller fast twitch fibers and
      lower succinate dehydrogenase activity. The latter finding suggests that
      mitochondrial content of muscle is reduced in heart failure and that impaired
      aerobic-oxidative capacity may play a role in the limitation of systemic exercise
      capacity.

PMID- 8522688
TI  - Analysis of beta-adrenergic receptor mRNA levels in human ventricular biopsy
      specimens by quantitative polymerase chain reactions: progressive reduction of
      beta 1-adrenergic receptor mRNA in heart failure.
AB  - OBJECTIVES: This study investigated the relation between the severity of heart
      failure and the extent of the reduction of beta 1-adrenergic receptor messenger
      ribonucleic acid (mRNA) levels in biopsy specimens from the ventricular septum
      obtained during cardiac catheterization of patients with various degrees of heart
      failure. BACKGROUND: Heart failure is accompanied by desensitization of the beta
      adrenergic receptor system, which is in part due to downregulation of beta 1
      adrenergic receptors. Downregulation of beta 1-adrenergic receptors has been
      suggested to be caused by reductions in mRNA levels. METHODS: Because biopsy
      specimens were small and receptor mRNAs not abundant, mRNA levels were determined
      by quantitative reverse transcription/polymerase chain reactions. This method was
      validated by measuring synthetic ribonucleic acid (RNA) standards and samples
      from explanted hearts by solution hybridization assays. Both methods yielded
      similar results, but the polymerase chain reaction method was approximately 1,000
      fold more sensitive. Sources of variations in the polymerase chain reaction were
      quantitated and found to be best controlled for by determination of the
      glyceraldehyde phosphate dehydrogenase mRNA as an endogenous control. RESULTS:
      Beta 1-adrenergic receptor mRNA levels in the biopsy specimens were decreased by
      7% in mild (New York Heart Association functional class II), 26% in moderate
      (functional class III) and > 50% in severe heart failure (functional class IV).
      There was a good correlation between hemodynamic indicators of heart failure and
      beta 1-adrenergic receptor mRNA levels. In contrast, beta 2-adrenergic receptor
      mRNA levels were apparently unaffected by heart failure. CONCLUSIONS: Reduced
      beta 1-adrenergic receptor mRNA levels occur early in heart failure and can be
      detected in septal biopsy specimens during right heart catheterization. The
      reduction in beta 1-adrenergic receptor expression may contribute to further loss
      of cardiac function.

PMID- 8522689
TI  - Prospective evaluation of hemostatic predictors of subacute stent thrombosis
      after coronary Palmaz-Schatz stenting.
AB  - OBJECTIVES: This study sought to investigate hemostatic predictors of subacute
      occlusive coronary stent thrombosis. BACKGROUND: Better hemostatic monitoring may
      improve antithrombotic therapy after stenting. METHODS: In 140 consecutive
      patients undergoing Palmaz-Schatz stent implantation for suboptimal angioplasty
      results, we obtained serial blood samples immediately before and daily for 12
      days after stenting. We prospectively tested the hypothesis that subacute stent
      thrombosis was more frequent if the surface expression of the inducible
      fibrinogen receptor on platelets (flow cytometry) or the concentration of plasma
      fibrinogen or that of the prothrombin fragments F1 + 2 before stent implantation
      exceeded the 75th percentile of the entire study cohort. RESULTS: All five stent
      occlusions encountered during the study occurred in patients with platelet
      fibrinogen receptor expression above the 75th percentile. Thus, the rate of stent
      occlusion differed significantly between the groups defined by platelet
      fibrinogen receptor expression (14.3% vs. 0%, p = 0.0008). In both the group with
      fibrinogen concentration and that with F1 + 2 concentration above the 75th
      percentile, three stent occlusions occurred. Between the groups defined by these
      variables, the rate of stent occlusion did not differ significantly (8.6% vs.
      1.9%, p = 0.10). Logistic regression analysis, including angiographic and
      hemostatic variables, confirmed platelet fibrinogen receptor expression as an
      independent predictor of stent occlusion (p = 0.020). Stent occlusion could not
      be predicted by the time course of any of the hemostatic variables. CONCLUSIONS:
      Platelet fibrinogen receptor expression is an independent predictor of subacute
      stent occlusion. However, fibrinogen and F1 + 2 concentrations do not show a
      strong relation to the risk of stent occlusion.

PMID- 8522690
TI  - A potential clinical method for calculating transmural left ventricular filling
      pressure during positive end-expiratory pressure ventilation: an intraoperative
      study in humans.
AB  - OBJECTIVES: This study sought to investigate whether right atrial pressure could
      be used to estimate pericardial pressure during positive end-expiratory pressure
      (PEEP). BACKGROUND: Because of elevated intrathoracic pressure during PEEP,
      pulmonary capillary wedge pressure may not accurately reflect left ventricular
      preload. An estimate of pericardial pressure during PEEP would allow assessment
      of transmural filling pressure. METHODS: In eight patients, at the start of
      cardiac surgery, pericardial and pleural pressures were recorded by balloon
      transducers placed over the anterolateral left ventricular wall. We also recorded
      intravascular pressures and left ventricular short-axis area by transesophageal
      echocardiography. RESULTS: A stepwise increase in PEEP from 0 to 15 cm H2O caused
      a linear increase in pleural pressure from 0.3 +/- 0.6 (mean +/- SEM) to 6.1 +/-
      0.8 mm Hg (p < 0.01). Pericardial pressure increased from 2.3 +/- 0.5 to 5.9 +/-
      0.6 mm Hg (p < 0.01). The correlation between right atrial (Pra) and pericardial
      pressure (Pperic) was good: Pra = 0.85 x Pperic + 1.8, r = 0.77. The correlation
      between changes in right atrial pressure and in pericardial pressure was better:
      delta Pra = 0.96 x delta Pperic -0.2, r = 0.97. Pulmonary capillary wedge
      pressure increased with PEEP (p < 0.05), whereas left ventricular area decreased
      (p < 0.05). However, there was a progressive reduction in transmural pressure,
      calculated as wedge pressure minus pericardial pressure (p < 0.05), and in
      transmural pressure, estimated as wedge pressure minus right atrial pressure (p <
      0.05). The estimated transmural filling pressure correlated (r = 0.86) with end
      diastolic area. CONCLUSIONS: The present observations suggest that right atrial
      pressure may be used to estimate changes in pericardial pressure with PEEP and
      that pulmonary capillary wedge pressure minus right atrial pressure is a
      potentially clinically useful approximation of transmural filling pressure.

PMID- 8522691
TI  - New method for accurate calculation of regurgitant flow rate based on analysis of
      Doppler color flow maps of the proximal flow field. Validation in a canine model
      of mitral regurgitation with initial application in patients.
AB  - OBJECTIVES: The purpose of this study was to develop a rational and objective
      method for selecting a region in the proximal flow field where the hemispheric
      formula for calculating regurgitant flow rates by the flow convergence technique
      is most accurate. BACKGROUND: A major obstacle to clinical implementation of the
      proximal flow convergence method is that it assumes hemispheric isovelocity
      contours throughout the Doppler color flow map, whereas contour shape depends
      critically on location in the flow field. METHODS: Twenty mitral regurgitant flow
      rate stages were produced in six dogs by implanting grommet orifices into the
      anterior mitral leaflet and varying driving pressures so that actual peak flow
      rate could be determined from the known effective regurgitant orifice times the
      orifice velocity. Because plotting flow rate calculated by using a hemispheric
      formula versus alias velocities produces underestimation near the orifice and
      overestimation far from it, this plot was fitted to a polynomial function to
      allow identification of an inflection point within a relatively flat intermediate
      zone, where factors causing overestimation and underestimation are expected to be
      unimportant or balanced. The accuracy of flow rate calculation by the inflection
      point was compared with unselective and selective averaging techniques. Clinical
      relevance, initial feasibility and correlation with an independent measure were
      tested in 13 consecutive patients with mitral regurgitation who underwent cardiac
      catheterization. RESULTS: 1) The accuracy of single-point calculations was
      improved by selecting points in the flat portion of the curve (y = 1.15x - 3.34,
      r = 0.87, SEE = 22.1 ml/s vs. y = 1.34x - 1.99, r = 0.71, SEE = 45.6 ml/s, p <
      0.01). 2) Selective averaging of points in the flat portion of the curve further
      improved accuracy and decreased scatter compared with unselective averaging (y =
      1.08x + 4.8, r = 0.96, SEE = 11.6 ml/s vs. y = 1.30x + 0.6, r = 0.90, SEE = 20.9
      ml/s, p < 0.01). 3) The proposed algorithm for mathematically identifying the
      inflection point provided the best results (y = 0.96x + 4.5, r = 0.96, SEE = 9.9
      ml/s), with a mean error of 1.6 +/- 9.7 ml/s vs. 11.4 +/- 11.7 ml/s for selective
      averaging (p < 0.01). In patients, the proposed algorithm identified an
      inflection point at which calculated regurgitant volume agreed best with invasive
      measurements (y = 1.1x - 0.61, r = 0.93, SEE = 17 ml). CONCLUSIONS: The accuracy
      of the proximal flow convergence method can be significantly improved by
      analyzing the flow field mathematically to identify the optimal isovelocity zone
      before using the hemispheric formula to calculate regurgitant flow rates. Because
      the proposed algorithm is objective, operator independent and, thus, suitable for
      automatization, it could provide the clinician with a powerful quantitative tool
      to assess valvular regurgitation.

PMID- 8522692
TI  - Left ventricular function in patients with coronary artery disease assessed by
      gated tomographic myocardial perfusion images. Comparison with assessment by
      contrast ventriculography and first-pass radionuclide angiography.
AB  - OBJECTIVES: This study evaluated the use of gated single-photon emission computed
      tomographic (SPECT) myocardial perfusion images for determination of left
      ventricular ejection fraction. BACKGROUND: Gated SPECT has expanded the
      applications of myocardial perfusion imaging to include the evaluation of left
      ventricular size, regional wall motion and regional systolic thickening. Accurate
      automated or semi-automated methods for quantitation of left ventricular ejection
      fraction from tomographic perfusion images would provide additional valuable
      clinical information. METHODS: Rest gated SPECT was performed on the stress
      distribution of technetium-99m sestamibi, using eight frames per cardiac cycle.
      Mid-horizontal long-axis and vertical long-axis gated tomographic perfusion
      images were analyzed after digital matrix inversion, which enhances edge
      detection, for ejection fraction determination. These ejection fractions were
      compared with those determined by contrast ventriculography (n = 54, including 45
      biplane and 9 single plane) and first-pass radionuclide angiography (n = 38) in
      patients with coronary artery disease. RESULTS: Myocardial perfusion SPECT image
      inversion-derived ejection fractions were slightly lower (2.7 ejection fraction
      units, p < 0.01), and first-pass ejection fractions were much lower (8.0 ejection
      fraction units, p < 0.001) than those obtained with contrast ventriculography.
      There was excellent correlation between SPECT and contrast ventriculographic
      ejection fractions (r = 0.93) over a wide range of ejection fractions (14% to
      89%). Good correlation was also observed between first-pass radionuclide
      angiography and both contrast ventriculography (r = 0.83) and SPECT (r = 0.87).
      Reproducibility of SPECT image inversion ejection fractions was excellent
      (intraobserver r = 0.99, interobserver r = 0.93). CONCLUSIONS: Semiautomated
      ejection fractions can be obtained from gated SPECT technetium-99m sestamibi
      perfusion images using the image inversion technique. These results are
      reproducible and correlate well with results of first-pass radionuclide
      angiography but are closer in value to those obtained with contrast
      ventriculography.

PMID- 8522693
TI  - A new Doppler method for quantification of volumetric flow: in vivo validation
      using color Doppler.
AB  - OBJECTIVES: This study was designed to assess the accuracy of a new Doppler
      method for quantification of volumetric flow in vivo. BACKGROUND: Noninvasive
      assessment of volumetric flow through heart valves and the great vessels remains
      a clinical goal. We present a new method for quantification of volumetric flow
      based on color Doppler mapping that computes velocity vectors over a surface
      normal to the point of scanning. This Doppler technique assumes only the
      incompressibility of the fluid. The method is basically independent of the angle
      of incidence between the ultrasound beam and the direction of blood flow and
      includes variations of flow area. METHODS: The color Doppler method was tested in
      seven anesthetized pigs by measuring pulmonary volumetric flows using multiplane
      Doppler echocardiography. The results were compared with those obtained by the
      thermodilution technique. In addition, volumetric flows across the mitral valve
      were determined in 10 normal volunteers by transthoracic Doppler echocardiography
      and compared with flows obtained with velocity-encoded magnetic resonance imaging
      (MRI). RESULTS: The mean value of the differences between the thermodilution
      technique and color Doppler were -0.16 +/- 0.94 liter/min for pulmonary
      volumetric flows (mean value of differences for [Thermodilution-Color Doppler] +/
      2 SD of differences). The mean value of the differences between MRI and color
      Doppler were 0.21 +/- 0.83 liter/min for mitral valvular volumetric flows (mean
      value of differences for [MRI-Color Doppler] +/- 2 SD of differences).
      CONCLUSIONS: The method showed close agreement with thermodilution and MRI for
      assessment of volumetric flow in vivo. It is therefore a noninvasive method with
      potential applications for cardiac output measurement and for quantification of
      volumetric flow of valvular insufficiency and restrictive lesions.

PMID- 8522694
TI  - Effect of ligation of patent ductus arteriosus on left ventricular performance
      and its determinants in premature neonates.
AB  - OBJECTIVES: The purpose of this study was to determine in preterm newborn infants
      the effects of ductal ligation on ventricular performance and its determinants:
      preload, afterload and contractility. BACKGROUND: Neonatal ventricular
      performance is highly sensitive to afterload. Therefore, the increase in systemic
      vascular resistance associated with ligation of a patent ductus arteriosus might
      worsen ventricular performance in the preterm infant. METHODS: All 14 premature
      infants undergoing patent ductus arteriosus ligation in a 1-year period at our
      institution underwent echocardiography at three times: before, immediately after
      and 24 h after ligation. Indexes studied included ventricular performance
      (fractional area change), preload (left ventricular end-diastolic dimension),
      afterload (end-systolic wall stress) and contractility (the difference between
      the measured and predicted velocity of circumferential fiber shortening). Blood
      pressure was measured; systemic resistance was calculated. These data were
      compared with those of 14 preterm infants without patent ductus arteriosus.
      RESULTS: The infants with patent ductus arteriosus had higher values for
      ventricular performance (mean +/- SD fractional area change 60 +/- 9% vs. 52 +/-
      11%, p < 0.05) and lower values for wall stress (22 +/- 6 vs. 44 +/- 17 g/cm2, p
      < 0.05) before ligation than did the control group. At 24 h after ligation,
      ventricular performance was not significantly changed (fractional area change 60
      +/- 9% to 57 +/- 12%). There were significant increases in blood pressure and
      systemic vascular resistance but no changes in wall stress or contractility.
      CONCLUSIONS: Ventricular performance is higher in premature infants with than in
      those without patent ductus arteriosus because afterload is lower in the former
      group. Although ductal ligation increases blood pressure and systemic resistance,
      wall stress and ventricular performance are maintained. Our results suggest that
      the premature newborn maintains ventricular performance during stress, at least
      in part, by manipulating afterload.

PMID- 8522695
TI  - Tetralogy of Fallot with pulmonary atresia associated with chromosome 22q11
      deletion.
AB  - OBJECTIVES: The purpose of this study was to clarify characteristics of tetralogy
      of Fallot and pulmonary atresia associated with chromosome 22q11 deletion.
      BACKGROUND: DiGeorge syndrome and conotruncal anomaly facies syndrome are
      associated with chromosome 22q11 deletion (hemizygosity). Associated cardiac
      anomalies include tetralogy of Fallot, truncus arteriosus and interrupted aortic
      arch. METHODS: Twenty-three patients with tetralogy of Fallot and pulmonary
      atresia were proved to have chromosome 22q11 deletion with fluorescent in situ
      hybridization using N25 probe (Oncor). Cardiovascular anomalies were compared
      with those in 26 patients with tetralogy of Fallot and pulmonary atresia without
      the deletion. Cardiovascular anomalies were studied with cardiac catheterization,
      cineangiography and echocardiography. RESULTS: In patients with 22q11 deletion,
      additional anomalies of the aortic arch, ductus arteriosus and pulmonary artery
      were more common as follows: right aortic arch (70% with deletion vs. 23% without
      deletion), high aortic arch reaching third rib (43% vs. 15%), aberrant left
      subclavian artery (35% vs. 0%), absent ductus arteriosus (83% vs. 46%), major
      aortopulmonary collateral arteries (91% vs. 50%), absent confluent central
      pulmonary arteries (48% vs. 4%). CONCLUSIONS: In patients with tetralogy of
      Fallot and pulmonary atresia, additional anomalies of the aortic arch, ductus
      arteriosus and pulmonary arteries are more common in patients with than in those
      without the 22q11 deletion.

PMID- 8522696
TI  - Evaluation of aortic regurgitation with digitally determined color Doppler-imaged
      flow convergence acceleration: a quantitative study in sheep.
AB  - OBJECTIVES: The aim of the present study was to validate a digital color Doppler
      based centerline velocity/distance acceleration profile method for evaluating the
      severity of aortic regurgitation. BACKGROUND: Clinical and in vivo experimental
      applications of the flow convergence axial centerline velocity/distance profile
      method have recently been used to estimate regurgitant flow rates and regurgitant
      volumes in the presence of mitral regurgitation. METHODS: In six sheep, a total
      of 19 hemodynamic states were obtained pharmacologically 14 weeks after the
      original operation in which a portion of the aortic noncoronary (n = 3) or right
      coronary (n = 3) leaflet was excised to produce aortic regurgitation.
      Echocardiographic studies were performed to obtain complete proximal axial flow
      acceleration velocity/distance profiles during the time of peak regurgitant flow
      (usually early in diastole) for each hemodynamic state. For each steady state,
      the severity of aortic regurgitation was assessed by measurement of the magnitude
      of the regurgitant flow volume/beat, regurgitant fraction and instantaneous
      regurgitant flow rates determined by using both aortic and pulmonary artery
      electromagnetic flow probes. RESULTS: Grade I regurgitation (regurgitant
      volume/beat < 15 ml, six conditions), grade II regurgitation (regurgitant
      volume/beat between 16 ml and 30 ml, five conditions) and grade III-IV
      regurgitation (regurgitant volume/beat > 30 ml, eight conditions) were clearly
      separated by using the color Doppler centerline velocity/distance profile domain
      technique. Additionally, an equation for correlating "a" (the coefficient from
      the multiplicative curve fit for the velocity/distance relation) with the peak
      regurgitant flow rates (Q [liters/min]) was derived showing a high correlation
      between calculated peak flow rates by the color Doppler method and the actual
      peak flow rates (Q = 13a + 1.0, r = 0.95, p < 0.0001, SEE = 0.76 liters/min).
      CONCLUSIONS: This study, using quantified aortic regurgitation, demonstrates that
      the flow convergence axial centerline velocity/distance acceleration profile
      method can be used to evaluate the severity of aortic regurgitation.

PMID- 8522697
TI  - Angiotensin-converting enzyme inhibition limits dysfunction in adjacent
      noninfarcted regions during left ventricular remodeling.
AB  - OBJECTIVES: We hypothesized that angiotensin-converting enzyme inhibitors would
      limit dysfunction in the first 8 weeks after transmural infarction in adjacent
      noninfarcted regions, as well as attenuate left ventricular remodeling.
      BACKGROUND: Angiotensin-converting enzyme inhibition limits ventricular dilation
      and hypertrophy and improves survival after anterior infarction, but its effect
      on regional function during remodeling is not well characterized. METHODS:
      Thirteen sheep underwent coronary ligation to create an anteroapical infarction.
      At postinfarction day 2, eight sheep were randomized to therapy with the
      angiotensin-converting enzyme inhibitor ramipril, and five sheep received no
      therapy. Animals were studied with magnetic resonance myocardial tagging before
      and 8 weeks after infarction. Left ventricular volume, mass and ejection fraction
      were measured, as were changes in percent circumferential shortening within the
      subendocardium and subepicardium of infarcted and noninfarcted myocardium, both
      adjacent to and remote from the infarction. RESULTS: Angiotensin-converting
      enzyme inhibition limited the increase in end-diastolic volume from a mean (+/-
      SD) of +1.5 +/- 0.7 ml/kg in control animals to +0.5 +/- 0.8 ml/kg in the treated
      group (p < 0.04). Segmental function within infarcted and remote noninfarcted
      tissue did not differ between groups. However, angiotensin-converting enzyme
      inhibition limited the decline in function in the adjacent noninfarcted region 8
      weeks after infarction. Percent circumferential shortening in the subendocardium
      decreased by -13 +/- 5% in the control group compared with -5 +/- 5% in the
      treated group (p < 0.03). CONCLUSIONS: In concert with a reduction in left
      ventricular remodeling after anterior infarction, angiotensin-converting enzyme
      inhibition limits the decline in function in the adjacent noninfarcted region.
      Dysfunction in adjacent noninfarcted regions may be an important determinant of
      left ventricular remodeling after infarction.

PMID- 8522698
TI  - Transvenous procurement of pulmonary artery smooth muscle and endothelial cells
      using a novel endoarterial biopsy catheter in a canine model.
AB  - OBJECTIVES: The aim of this study was to evaluate the performance of a new
      arterial biopsy catheter in obtaining pulmonary endovascular samples in a canine
      model. BACKGROUND: Percutaneous endomyocardial biopsy is a widely used and
      valuable procedure in the management of posttransplant rejection and selected
      cardiomyopathies. A similar method of obtaining endoarterial biopsy samples would
      aid in the study, diagnosis and management of arterial diseases. METHODS:
      Catheterization was performed in 19 dogs, each weighing 20 to 30 kg, through an
      8F sheath in the external jugular vein to obtain pulmonary endoarterial samples.
      The catheter consists of two sliding tubes: an inner one with a beveled opening
      that accommodates endoarterial tissue by means of a vacuum and an outer tube with
      a sharp distal edge that cuts the tissue when activated. RESULTS: Overall, a
      total of 266 separate biopsy attempts were performed, and 161 tissue samples were
      obtained (success rate 61%). With modifications in technique in the last nine
      dogs, 54 (93%) of 58 attempts were successful. There were no deaths,
      extravasation of contrast material on angiography or thrombi. Of 20 vessels with
      prebiopsy and postbiopsy angiograms, 1 developed transient spasm (5%). On
      microscopic examination of cross sections of 50 separate pulmonary endoarterial
      biopsy samples, all had smooth muscle cells and 30 contained endothelial cells
      (60%). The arteries of origin showed small intimal and medial tears and mild
      perivascular hemorrhage. Angiographic and pathologic examination of previously
      biopsied arterial segments 2 weeks (two dogs) and 8 weeks (two dogs) after the
      procedure showed patent vessels and no thrombi. Histologically, the biopsy sites
      revealed mild neointimal and medial proliferation. CONCLUSIONS: This new
      endoarterial biopsy catheter is safe and effective in obtaining pulmonary artery
      samples in normotensive dogs.

PMID- 8522699
TI  - Subacute occlusion, bleeding complications, hospital stay and restenosis after
      Palmaz-Schatz coronary stenting under a new antithrombotic regimen.
AB  - OBJECTIVES: This study was designed to evaluate the effect of an antithrombotic
      regimen without full early anticoagulation on subacute occlusion, bleeding,
      hospital stay and restenosis after elective coronary stenting. BACKGROUND:
      Subacute occlusion is a major limitation of stenting. Aggressive antithrombotic
      therapy is not fully prophylactic against this complication, carries risk of
      bleeding, prolongs hospital stay and reduces cost-effectiveness. METHODS: We
      studied 110 consecutive patients (121 lesions) who underwent elective Palmaz
      Schatz stenting. Intravenous heparin was given only during the procedure. After
      stenting, patients took aspirin, dipyridamole, dextran, warfarin and low
      molecular weight heparin (enoxaparin, 40 mg subcutaneously daily, stopped when an
      international normalized ratio of 2 to 3 was achieved). The first 52 patients
      (group A) underwent coronary angiography 24 h after stenting, and hospital stay
      was extended until an international normalized ratio of 2 to 3.5 was achieved.
      The remaining 58 patients (group B) were discharged 24 h after stenting. Clinical
      and angiographic follow-up were performed 1 and 6 months after stenting for all
      patients. RESULTS: In group A the activated partial thromboplastin time remained
      normal (30 +/- 6.2 s [mean +/- SD]) during enoxaparin administration, and
      hospital stay was 9.1 +/- 4.3 days. In group B hospital stay was 27 +/- 8 h. No
      major cardiac events occurred within the first month in patients from both
      groups. At 1 and 30 days all stented lesions remained patent. Only two patients
      (1.8%, 95% confidence interval [CI] 0.32% to 7%) developed bleeding. At 6 months,
      the restenosis rate was 22% (95% CI 15% to 30%). CONCLUSIONS: After coronary
      stenting with optimal angiographic results, this new antithrombotic regimen
      prevented subacute stent occlusion and bleeding, with a brief hospital stay. No
      detrimental effect on the previously reported restenosis rate was observed.

PMID- 8522701
TI  - The face of death--grim reaper or rite of passage?

PMID- 8522700
TI  - Activation of adenosine receptors before ischemia enhances tolerance against
      myocardial stunning in the rabbit heart.
AB  - OBJECTIVES: This study examined whether stimulation of adenosine receptors before
      ischemia enhances myocardial resistance to stunning in vivo. BACKGROUND: We
      previously demonstrated the attenuation of myocardial stunning by ischemic
      preconditioning through adenosine receptor activation in rabbits. METHODS: 1) To
      confirm the efficacy of an intravenous infusion of adenosine to stimulate
      adenosine receptors in the heart, we assessed the effect of an adenosine infusion
      on the inotropic response to an isoproterenol challenge. 2) Myocardial stunning
      was induced by 10 min of coronary occlusion and reperfusion. The regional
      thickening fraction was monitored by an epicardial Doppler sensor. Rabbits were
      pretreated with either no drug (control group), adenosine, 8-phenyltheophylline
      or a combination of 8-phenyltheophylline plus adenosine. RESULTS: An intravenous
      infusion of adenosine at 0.15 mg/kg body weight per min attenuated by 50% the
      elevation of left ventricular dP/dtmax by isoproterenol (0.075 microgram/kg per
      min). The same dose of adenosine infused for 15 min before ischemia significantly
      improved the postischemic recovery of the thickening fraction, and the thickening
      fraction at 30 min reperfusion was 76.8 +/- 3.3% (mean +/- SE) of the baseline
      value, which was significantly higher than the control value (42.9 +/- 4.5%). The
      relation between thickening fraction and systolic left ventricular pressure after
      reperfusion was shifted toward higher thickening fraction by adenosine. This
      beneficial effect of adenosine was not detected in rabbits given 8
      phenyltheophylline before adenosine, and 8-phenyltheophylline-treated rabbits
      showed a time course of thickening fraction similar to that in the control group.
      CONCLUSIONS: An intravenous infusion of adenosine is capable of protecting rabbit
      hearts against stunning through adenosine receptor activation.

PMID- 8522702
TI  - President's page: quantity and quality--Is 75 the answer?

PMID- 8522703
TI  - Signal-averaged electrocardiography.

PMID- 8522704
TI  - Recommended criteria for expert witnesses. Board of Governors' Ad Hoc Task Force
      to develop recommendations for malpractice reform. American College of
      Cardiology.

PMID- 8522705
TI  - Transesophageal echocardiography versus oral anticoagulation before electrical
      cardioversion of atrial fibrillation: what about atrial clot size?

PMID- 8522706
TI  - Long-term clinical benefit of dynamic cardiomyoplasty.

PMID- 8522707
TI  - Coronary angioplasty ameliorates hypoperfusion-induced endothelial dysfunction in
      patients with stable angina pectoris.
AB  - OBJECTIVES: This study sought to investigate the effect of coronary angioplasty
      on chronic hypoperfusion-induced endothelial dysfunction in patients with
      coronary heart disease. BACKGROUND: The endothelium is an important component for
      organ flow regulation. Ischemia with or without reperfusion is known to cause
      endothelial dysfunction. We tested the hypothesis that chronic hypoperfusion
      impairs endothelial function in the angiographically normal coronary artery
      segment distal to stenosis and that the impairment by chronic hypoperfusion is
      reduced by coronary angioplasty. METHODS: In 13 patients with stable angina
      pectoris, substance P (10, 30 and 100 pmol) and nitroglycerin (200 micrograms)
      were sequentially infused into the coronary artery in a cumulative manner on the
      day after coronary angioplasty. In 10 of these patients, vascular responses to
      these agents were again investigated 3 months after angioplasty. Changes in
      vascular diameter were evaluated in vessels located proximal and distal to the
      target lesion, both of which were angiographically normal, by performing computer
      assisted quantitative coronary angiography. In five patients, the transstenotic
      pressure gradient was also measured with a pressure sensor-mounted guide wire
      before angioplasty. RESULTS: On the day after angioplasty, the magnitude of
      dilation by substance P in distal segments was significantly less than that in
      proximal segments and inversely correlated with the transstenotic pressure
      gradient (p < 0.05) and lesion stenosis (p < 0.05). There was no difference in
      nitroglycerin-induced vasodilation between the two vessel segment groups. Three
      months later, the impaired response to substance P in the distal segment was
      restored to normal. CONCLUSIONS: We conclude that chronic hypoperfusion impairs
      endothelium-dependent dilation of coronary artery distal to critical stenosis in
      patients with ischemic heart disease and that coronary angioplasty ameliorates
      the endothelial dysfunction within 3 months.

PMID- 8522708
TI  - Clinical observation of spontaneous anginal attacks and multivessel spasm in
      variant angina pectoris with normal coronary arteries: evaluation by 24-hour 12
      lead electrocardiography with computer analysis.
AB  - OBJECTIVES: Using a new, computerized 24-h 12-lead electrocardiographic (ECG)
      recording and analysis system (the EAGLE system), we sought to evaluate the
      clinical manifestations of ischemic episodes in patients with variant angina and
      normal coronary arteries. BACKGROUND: Although the prognosis of variant angina
      without significant organic stenosis is generally good, the incidence of
      multivessel spasm, a major prognostic factor, is surprisingly high in provocation
      tests. METHODS: A total of 122 patients with suspected variant or unstable angina
      underwent 24-h examination with the EAGLE system and two-channel Holter
      monitoring. Thirty patients in this group were diagnosed as having variant angina
      with normal or nearly normal coronary arteries. Twenty-two (73%) of these 30
      patients developed anginal attacks with ST segment elevation during monitoring
      and were enrolled in the study. RESULTS: The 22 patients had a total of 138
      episodes of transient ST segment elevation and 13 episodes of ST segment
      depression. No arrhythmias were observed during ST segment depression, but 26
      episodes of ST segment elevation (19%) were associated with arrhythmias: 7 with
      premature ventricular contractions, 3 with ventricular bigeminy, 3 with complete
      atrioventricular (AV) block, 1 with complete AV block and couplets of premature
      ventricular contractions and 12 with marked sinus bradycardia (< 45 beats/min).
      Ten (45%) of the 22 patients had multivessel spasm. We observed three different
      patterns of multivessel spasm: 1) spasm at a different site on different
      occasions (migratory spasm); 2) spasm that sequentially affected two different
      sites; 3) simultaneous spasm at more than one site. The duration of ST segment
      elevation was much longer in patients with sequential and simultaneous spasm than
      in those with single-vessel spasm, and arrhythmias were more frequent during
      these two types of multivessel spasm. CONCLUSIONS: Although the prognosis of
      multivessel spasm is believed to be poor, this may not necessarily be so. Anginal
      attacks due to sequential and simultaneous multivessel spasm seem to be more
      dangerous than those involving single-vessel spasm or migratory multivessel
      spasm.

PMID- 8522709
TI  - Diffuse disorder of coronary artery vasomotility in patients with coronary
      spastic angina. Hyperreactivity to the constrictor effects of acetylcholine and
      the dilator effects of nitroglycerin.
AB  - OBJECTIVES: We examined the vasomotility of the entire epicardial coronary artery
      system in patients with and without coronary spastic angina. BACKGROUND: The
      coronary arteries of patients with variant angina are hyperreactive to diverse
      constrictor stimuli. It is unclear whether the abnormal responses to constrictive
      or dilative stimuli, or both, result from a localized or diffuse disorder in the
      coronary artery tree. METHODS: Coronary artery diameter responses to
      intracoronary acetylcholine and nitroglycerin were examined at the proximal,
      middle and distal segments of three principal coronary arteries in 36 patients
      with coronary spastic angina without significant stenosis and in 12 young (< or =
      30 years old) and 20 older control subjects (> 30 years old) with normal coronary
      arteriographic findings. In 10 patients with significant coronary stenosis, the
      responses of the prestenotic segments were also examined. RESULTS: In patients
      with coronary spastic angina, coronary spasm was induced in 23 left anterior
      descending, 13 left circumflex and 17 right coronary arteries by acetylcholine.
      Multivessel spasm was observed in 15 patients. Acetylcholine had a dilator effect
      on most segments in young control subjects and a mild constrictor effect in older
      control subjects and in patients with significant stenosis. Comparison of the
      responses to acetylcholine among groups demonstrated that the constrictor
      response of the artery with spasm was enhanced significantly and diffusely. That
      of the artery without spasm also tended to be enhanced. Coronary artery diameters
      after nitroglycerin did not differ in any segment among patients with coronary
      spastic angina and both control groups. In patients with coronary spastic angina,
      nitroglycerin significantly enhanced dilation in all segments of the artery with
      spasm compared with that observed in both control groups and in most segments of
      the artery without spasm. Patients with significant coronary stenosis had a
      reduced response compared with that in control subjects. CONCLUSIONS:
      Hyperreactive responses not only to the constrictor effects of acetylcholine, but
      also the dilator effects of nitroglycerin were detected diffusely in the
      epicardial coronary arteries of patients with coronary spastic angina. This
      finding indicates that a diffuse, not localized, disorder in vasomotility is
      involved in the pathogenesis of coronary spastic angina.

PMID- 8522710
TI  - Predictive value of wavelet correlation functions of signal-averaged
      electrocardiogram in patients after anterior versus inferior myocardial
      infarction.
AB  - OBJECTIVES: This study sought to evaluate the prognostic value of wavelet
      correlation functions of the signal-averaged electrocardiogram (ECG) for
      arrhythmic events in patients after myocardial infarction. BACKGROUND: Wavelet
      transform of the signal-averaged ECG has been shown to be a nonstationary
      analysis technique describing the time evolution of frequency spectra throughout
      the QRS complex. To quantify the wavelet transform, we introduced the new concept
      of the wavelet correlation function. METHODS: The relation among wavelet
      correlation functions, ventricular late potentials and the site of infarction was
      investigated in 769 men < 66 years old who survived the acute phase of myocardial
      infarction (351 [46%] anterior, 418 [54%] inferior infarctions). Signal-averaged
      ECG recordings were obtained 2 to 3 weeks after infarction. During 6 months of
      follow-up, 33 patients (4.3%) experienced a malignant arrhythmic event. Wavelet
      correlation functions of the signal-averaged ECG were evaluated in a time
      frequency plane ranging from 25 ms before QRS onset to 25 ms after QRS offset in
      the frequency range between 40 and 100 Hz. RESULTS: Patients with an anterior
      infarction had lower mean wavelet correlation coefficients (p < 0.001) and a
      lower incidence of ventricular late potentials than patients with an inferior
      infarction (32.3% vs. 42.7%, p = 0.003). The combination of wavelet correlation
      functions and late potentials increased the total predictive accuracy from 52% to
      72% for inferior and from 64% to 76% for anterior infarctions. CONCLUSIONS:
      Spectral changes in the signal-averaged QRS complex are more prominent in
      anterior than inferior infarctions. Combination of late potential analysis and
      wavelet correlation functions increases the prognostic value for serious
      arrhythmic events after myocardial infarction.

PMID- 8522711
TI  - Recanalization of Chronically Occluded Aortocoronary Saphenous Vein Bypass Grafts
      With Long-Term, Low Dose Direct Infusion of Urokinase (ROBUST): a serial trial.
AB  - OBJECTIVES: This multicenter study sought to evaluate the short-term efficacy and
      safety of prolonged, low dose, direct urokinase infusion in recanalization of
      chronically occluded saphenous vein bypass grafts in a large sample of patients,
      as well as to determine the 6-month patency rates for this procedure. BACKGROUND:
      Patients with chronically occluded aortocoronary vein grafts and uncontrolled
      angina pectoris have limited options for therapy. Previous work has shown that
      chronically occluded vein grafts can be recanalized by thrombolysis. METHODS: A
      coaxial infusion of urokinase (100,000 U/h) was given directly into occluded vein
      grafts in 107 patients. Balloon angioplasty was performed after lysis was
      achieved. Patients were discharged with warfarin and aspirin therapy. Six-month
      clinical follow-up data were obtained, and repeat angiography was encouraged.
      RESULTS: Initial patency was achieved in 74 patients (69%). Mean duration of
      infusion was 25.4 h, and mean urokinase dosage was 3.70 million U. Acute adverse
      events included acute myocardial infarction in 5 patients (5%), enzyme level
      elevation in 18 (17%), emergency coronary artery bypass graft surgery in 4 (4%),
      stroke in 3 (3%) and death in 7 (6.5%). Recanalization was unsuccessful in all
      seven patients who died. Six-month follow-up angiograms were obtained for 40
      patients (54%), 16 of whom maintained a patent graft (40%). Angina was present in
      13 patients with successful (22%) and 12 with unsuccessful (71%) recanalization
      at 6-month follow-up. CONCLUSIONS: Chronically occluded aortocoronary vein grafts
      can be recanalized in approximately 70% of appropriately selected patients.
      Complications are similar to those observed with repeat operations. Clinical
      follow-up shows an improvement in angina. This procedure is intended for patients
      with only one occluded vein graft. Strict adherence to the protocol will improve
      patency and reduce complications.

PMID- 8522712
TI  - Intravenous amiodarone for recurrent sustained hypotensive ventricular
      tachyarrhythmias. Intravenous Amiodarone Multicenter Trial Group.
AB  - OBJECTIVES: We sought to determine the response rate and safety of intravenous
      amiodarone in patients with ventricular tachyarrhythmias refractory to standard
      therapies. BACKGROUND: Numerous small retrospective reports suggest a response of
      refractory ventricular tachyarrhythmias to intravenous amiodarone, yet no
      controlled prospective trials exist. METHODS: Two hundred seventy-three patients
      with recurrent hypotensive ventricular tachyarrhythmias refractory to lidocaine,
      procainamide and bretylium were randomized to receive one of three doses of
      intravenous amiodarone: 525, 1,050 or 2,100 mg/24 h (mean [+/- SE] dose 743.7 +/-
      418.7, 1,175.2 +/- 483.7, 1,921.2 +/- 688.8 mg, respectively) by continuous
      infusion over 24 h. RESULTS: Of the 273 patients, 110 (40.3% response rate)
      survived 24 h without another hypotensive ventricular tachyarrhythmic event while
      being treated with intravenous amiodarone as a single agent (primary end point).
      A significant difference in the time to first recurrence of ventricular
      tachyarrhythmia (post hoc analysis) over the first 12 h was observed when the
      combined 1,050- and 2,100-mg dose groups were compared with the 525-mg dose group
      (p = 0.046). The number of supplemental (150 mg) infusions of intravenous
      amiodarone (given for breakthrough destabilizing tachyarrhythmias) during hours 0
      to 6 (prespecified secondary end point) was significantly greater in the 525-mg
      dose group than in the 2,100-mg dose group (1.09 +/- 1.57 vs. 0.51 +/- 0.97, p =
      0.0043). However, there was no clear dose-response relation observed in this
      trial with respect to success rates (primary end point), time to first recurrence
      of tachyarrhythmia (post hoc analysis) or mortality (secondary end point) over 24
      h. CONCLUSIONS: Intravenous amiodarone is a relatively safe therapy for
      ventricular tachyarrhythmias refractory to other medications.

PMID- 8522713
TI  - Diurnal pattern of QTc interval: how long is prolonged? Possible relation to
      circadian triggers of cardiovascular events.
AB  - OBJECTIVES: This study sought to evaluate the range and variability of the QT and
      corrected QT (QTc) intervals over 24 h and to assess their pattern and relation
      to heart rate variability. BACKGROUND: Recent Holter monitoring data have
      revealed a high degree of daily variability in the QTc interval. The pattern of
      this variability and its relation to heart rate variability remain poorly
      characterized. METHODS: We developed and validated a new method for continuous
      measurement of QT intervals from three-channel, 24-h Holter recordings. Average
      RR, QT, QTc and heart rate variability were measured from 5-min segments of data
      from 21 healthy subjects. RESULTS: Measurement of 6,048 segments showed mean (+/-
      SD) RR, QT and QTc intervals of 830 +/- 100, 407 +/- 23 and 445 +/- 16 ms,
      respectively (mean QTc interval for men 434 +/- 12 ms, 457 +/- 10 ms for women, p
      < 0.0001). The average maximal QTc interval was 495 +/- 21 ms and the average QTc
      range 95 +/- 20 ms. The maximal QTc interval was > or = 500 ms in 6 subjects and
      > or = 490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc
      interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and
      the high frequency component of heart rate variability were greater during sleep.
      Both the QTc interval and the variability between hourly minimal and maximal QTc
      intervals reached their circadian peak shortly after awakening, before declining
      to daytime levels. CONCLUSIONS: The maximal QTc interval over 24 h in normal
      subjects is longer than heretofore thought. Both QT and QTc intervals are longer
      during sleep. The QTc interval and QTc variability reach a peak shortly after
      awakening, which may reflect increased autonomic instability during early waking
      hours, and the time of the peak value corresponds in time to the period of
      reported increased vulnerability to ventricular tachycardia and sudden cardiac
      death. These findings have implications regarding the definition of QT
      prolongation and its use in predicting arrhythmias and sudden death.

PMID- 8522714
TI  - Changing outcome of angioplasty in the elderly.
AB  - OBJECTIVES: This study sought to determine whether in-hospital and intermediate
      term posthospital outcomes have changed in elderly patients undergoing
      percutaneous transluminal coronary angioplasty from the period 1980 through 1989
      to the period 1990 through 1992. BACKGROUND: Although elderly patients have a
      higher incidence of procedure-related deaths and late recurrence of angina after
      coronary angioplasty, recent complication rates for angioplasty seem to be lower.
      METHODS: From 1980 to 1989, 982 patients > or = 65 years old underwent
      nonemergent coronary angioplasty (group A). They were compared with 768 similar
      patients who had coronary angioplasty from 1990 to 1992 (group B). RESULTS:
      Patients in group B were older than those in group A and had a higher mean
      concomitant disease score, a higher proportion of men and a greater proportion of
      patients with a previous myocardial infarction and previous coronary artery
      bypass surgery. Despite the increased complexity of the group B cohort,
      procedural success rates were higher, and rates of important in-hospital
      complications were much lower than those in group A. For group A versus group B,
      respectively, the technical success rate was 88.1% versus 93.5% (p < 0.001), in
      hospital death rate 3.3% versus 1.4% (p = 0.014), emergency bypass surgery rate
      5.5% versus 0.65% (p < 0.001) and incidence of in-hospital death or myocardial
      infarction 6.3% versus 3.4% (p < 0.005). However, intermediate-term posthospital
      event-free rates in hospital survivors did not decrease. The rate of death or
      myocardial infarction at 6 months was 4.7% in group A versus 7.1% in group B (p <
      0.05). Survival free of acute myocardial infarction, bypass surgery, repeat
      coronary angioplasty or severe angina at 1 year was 66.7% in group A versus 54.9%
      in group B (p < 0.001). The combined in-hospital death/myocardial infarction rate
      plus that for the first 6 months after hospital dismissal was essentially
      equivalent for the two groups (10.3% vs. 9.9%, p = NS). CONCLUSIONS: An increase
      in technical success rates and a reduction in short-term complication rates for
      coronary angioplasty in the elderly in recent years have not translated into an
      improved event-free survival rate, which continues to be influenced by important
      baseline characteristics of these high risk patients.

PMID- 8522715
TI  - Assessment of reverse use-dependent blocking actions of class III antiarrhythmic
      drugs by 24-hour Holter electrocardiography.
AB  - OBJECTIVES: This clinical study was designed to compare rate-dependent effects of
      class III agents on QT prolongation. BACKGROUND: Clinical data that compare the
      electrophysiologic differences among class III agents with different selectivity
      for potassium channels are still lacking. METHODS: QT intervals were measured
      over a wide range of preceding RR intervals during sinus rhythm by 24-h Holter
      electrocardiography before and after oral administration of four class III
      agents: E4031, dofetilide, MS551 and d-sotalol. Rate-dependent changes in the QT
      interval were assessed by the slope of the linear regression line estimating the
      QT-square root of RR relation. RESULTS: All agents significantly increased the
      mean slope: E4031 increased the mean [+/- SD] value from 0.32 +/- 0.05 to 0.42 +/
      0.13 (p < 0.01), dofetilide from 0.32 +/- 0.03 to 0.50 +/- 0.12 (p < 0.03),
      MS551 from 0.35 +/- 0.06 to 0.45 +/- 0.10 (p < 0.02) and d-sotalol from 0.31 +/-
      0.05 to 0.33 +/- 0.04 (p < 0.05). However, in those patients given either E4031,
      dofetilide or MS551, the degree of QT prolongation was smaller at shorter square
      root of RR intervals and was better preserved at shorter square root of RR
      intervals by d-sotalol, with a smaller increase in slope (p < 0.02 vs. dofetilide
      and MS551). CONCLUSIONS: On ambulatory electrocardiography, reverse use
      dependence in QT prolongation was least prominent with d-sotalol among the four
      study drugs. In the range of physiologic heart rates, class III agents could
      manifest different profiles of rate dependence in their QT-prolonging effect.

PMID- 8522716
TI  - Optimal electrode position for transvenous defibrillation: a prospective
      randomized study.
AB  - OBJECTIVES: This study was performed to determine the optimal position for the
      proximal electrode in a two-electrode transvenous defibrillation system.
      BACKGROUND: Minimizing the energy required to defibrillate the heart has several
      potential advantages. Despite the increased use of two-electrode transvenous
      defibrillation systems, the optimal position for the proximal electrode has not
      been systematically evaluated. METHODS: Defibrillation thresholds were determined
      twice in random sequence in 16 patients undergoing implantation of a two-lead
      transvenous defibrillation system; once with the proximal electrode at the right
      atrial-superior vena cava junction (superior vena cava position) and once with
      the proximal electrode in the left subclavian-innominate vein (innominate vein
      position). RESULTS: The mean (+/- SD) defibrillation threshold with the proximal
      electrode in the innominate vein position was significantly lower than with the
      electrode in the superior vena cava position (13.4 +/- 5.7 J vs. 16.3 +/- 6.6 J,
      p = 0.04). Defibrillation threshold with the proximal electrode in the innominate
      vein position was lower or equal to that achieved in the superior vena cava
      position in 75% of patients. In patients with normal heart size (cardiothoracic
      ratio < or = 0.55), the improvement in defibrillation threshold with the proximal
      electrode in the innominate vein position was more significant than in patients
      with an enlarged heart (innominate vein 13.0 +/- 6.5 J vs. superior vena cava
      17.9 +/- 5.1 J, p < 0.01). In patients with an enlarged heart, no difference
      between the two sites was observed (innominate vein 13.9 +/- 4.5 J vs. superior
      vena cava 13.6 +/- 8.3 J, p = NS). CONCLUSIONS: During implantation of a two-lead
      transvenous defibrillation system, positioning the proximal defibrillation
      electrode in the subclavian-innominate vein will lower defibrillation energy
      requirements in the majority of patients.

PMID- 8522717
TI  - Natural history of severe atheromatous disease of the thoracic aorta: a
      transesophageal echocardiographic study.
AB  - OBJECTIVES: This study sought to prospectively observe the morphologic and
      clinical natural history of severe atherosclerotic disease of the thoracic aorta
      as defined by transesophageal echocardiography. BACKGROUND: Atherosclerosis of
      the thoracic aorta has been shown to be highly associated with risk for embolic
      events in transesophageal studies, but the natural history of the disease under
      clinical conditions has not been reported. METHODS: During a 20-month period, 191
      of 264 patients undergoing transesophageal echocardiography had adequate
      visualization of the aorta to allow atherosclerotic severity to be graded as
      follows: grade I = normal (44 patients); grade II = intimal thickening (52
      patients); grade III = atheroma < 5 mm (62 patients); grade IV = atheroma > or =
      5 mm (19 patients); grade V = mobile lesion (14 patients). All available patients
      with grades IV (8 patients) and V (10 patients) disease as well as a subgroup of
      12 patients with grade III disease had follow-up transesophageal
      echocardiographic studies (mean [+/- SD] 11.7 +/- 0.9 months, range 6 to 22).
      RESULTS: Of 30 patients undergoing follow-up transesophageal echocardiographic
      studies, 20 (66%) had no change in atherosclerotic severity grade. Of the
      remaining 10 patients, atherosclerotic severity progressed one grade in 7 and
      decreased in 3 with resolved mobile lesions. Of 18 patients with grade IV or V
      disease of the aorta who underwent a follow-up study, 11 (61%) demonstrated
      formation of new mobile lesions. Of 10 patients with grade V disease on initial
      study who underwent follow-up study, 7 (70%) demonstrated resolution of a
      specific previously documented mobile lesion. However, seven patients (70%) with
      grade V disease also demonstrated development of a new mobile lesion. Of 33
      patients with grade IV or V disease, 8 (24%) died during the study period, and 1
      (3%) had a clinical embolic event. CONCLUSIONS: The presence of severe
      atherosclerotic disease of the thoracic aorta as defined by transesophageal
      echocardiography is associated with a high mortality rate. Although the
      morphologic natural history of the disease process itself is marked by stability
      over a 1-year period, individual lesion morphology is dynamic, with formation and
      resolution of mobile components occurring frequently over the same period. The
      dynamic nature of individual lesion morphology potentially enhances the
      possibility of developing a successful therapeutic strategy.

PMID- 8522718
TI  - Resting energy expenditure in cancer patients.

PMID- 8522719
TI  - Pediatric dietary lipid guidelines: a policy analysis.
AB  - The 1992 AAP policy of dietary fat and cholesterol restrictions in all children
      over two is based on incomplete evidence. The low-fat diet has never been
      demonstrated to be beneficial for prepubescent healthy children, and the unguided
      rapid implementation of numerical guidelines could lead to ill effects. Caution
      in the face of incomplete data was the hallmark of the 1983 and 1986 AAP
      Committee positions. Subsequent AAP policy change should have awaited either the
      direct clinical evidence they had previously considered necessary to demonstrate
      efficacy or the more general availability of the dietary guidance needed for safe
      implementation of strict numerical guidelines. We are neither calling for
      paralysis of policy nor do we wish to imply that 30% dietary fat is necessarily
      unhealthful for children. However, we do foresee the need for greater nutritional
      guidance for parents. In the absence of better nutrition education, zealous
      parents could switch a 2-year old immediately to a low-fat regimen to such an
      extent that the child might not achieve adequate nutrient intake to assure
      optimal growth and development. Moreover, current changes in lifestyle result in
      less parental supervision in all spheres of behavior, making closer dietary
      supervision less likely. A prudent pediatric guideline should encourage
      moderation and the gradual reduction of dietary fat intake throughout the early
      childhood years, achieving the numerical standards set for adults during
      adolescence. Such a policy has not been shown to foster atherosclerosis or to
      provide the yoke of unhealthful dietary habits that must be broken in adulthood.

PMID- 8522720
TI  - Epidemiologic studies of antioxidants and cancer in humans.
AB  - To assess whether antioxidants may reduce the risk of cancer, we reviewed the
      epidemiologic literature from 1985 through 1993. We assessed the separate
      relationships of three antioxidants (carotenoids, vitamin C, and vitamin E) with
      six sites of cancer (lung, upper aerodigestive tract, uterine cervix, colon,
      breast, prostate). This review was limited to dietary intake or serum nutrient
      studies that met a predefined set of methodologic standards. We judged the
      evidence in support of causal relationships based upon consistency of results
      across studies, strength of association, and evidence of a dose-response
      relationship. The data concerning carotenoids and lung cancer risk were most
      consistent (protection found in 4 of 8 diet studies and 5 of 6 serum studies),
      with strong associations that tended to follow a dose-response pattern. For lung
      cancer, there was weaker evidence of protection from vitamin C (2 of 6 diet
      studies) and vitamin E (3 of 4 serum studies). For upper aerodigestive tract
      cancers (oral cavity, pharynx, or larynx), there was evidence of a protective
      effect of carotenoids (3 of 4 diet studies) and vitamin C (4 of 5 diet studies).
      For cancer of the uterine cervix, we found suggestive evidence of protection from
      vitamin C (4 of 5 diet studies) and perhaps carotenoids (2 of 5 diet studies).
      For cancers of the colon, breast, and prostate, the current data do not support a
      protective effect of antioxidants. More definite conclusions about the benefits
      of antioxidants in cancer prevention will be derived from on-going intervention
      trials.

PMID- 8522721
TI  - Role of dietary salt in hypertension.
AB  - Hypertension is the most common chronic disease in the United States and,
      untreated, results in disability or death due to stroke, heart failure or kidney
      failure. Fortunately the results of hypertension can be avoided to a large extent
      by proper treatment. One treatment which is effective in some cases is the
      restriction of dietary NaCl intake. This review considers the role of dietary
      NaCl in the genesis, therapy and prevention of hypertension. Most people can eat
      as much NaCl as they like; they have good kidneys which, within about 24 hours,
      excrete the NaCl as fast as it is taken in and nothing happens to blood pressure.
      A few, especially those with kidney disease, do not excrete it as fast as it is
      taken in and blood pressure rises. They are "salt sensitive". Once hypertension
      is established, the proportion who are "NaCl sensitive" is much higher. About 60%
      of people with hypertension respond to a high NaCl intake with a rise in pressure
      and to NaCl restriction with a fall in pressure and reduction in the need for
      antihypertensive medication. These are the same people that respond to diuretics
      with a fall in blood pressure. Many are black and elderly and have low plasma
      renin activity (low-renin hypertension) but some have normal or high plasma renin
      activity (normal or high-renin hypertension). Evidence suggests that very early
      they have a subtle kidney defect which causes them to excrete NaCl and water more
      slowly, e.g., even before they become hypertensive, black and elderly subjects
      excrete intravenously administered NaCl more slowly than white and young
      subjects. How does NaCl retention raise blood pressure? One possibility is that
      the NaCl retention causes water retention which releases a digitalis-like
      substance that increases the contractile activity of heart and blood vessels.
      Another is that the sodium itself penetrates the vascular smooth muscle cell,
      causing it to contract. "Salt sensitive" hypertension also responds to increased
      potassium and calcium intakes, perhaps in part because they increase NaCl urinary
      excretion.

PMID- 8522722
TI  - Calcium, magnesium and phosphorus in the nutrition of the newborn.
AB  - Several factors have been suggested to contribute to inadequate bone
      mineralization in infants. Calcium and phosphorus intakes in preterm infants are
      below the intrauterine accretion rates. Calcium retention is influenced by the
      types of calcium salts used and by alterations in dietary phosphorus, fat and
      carbohydrates. Dietary intakes of vitamin D, and modifications in the protein
      base of infant formula, e.g., soy base vs cow milk base, may impact bone
      mineralization. The major hormonal mechanisms involved in the regulation of bone
      mineralization are parathyroid hormone, calcitonin and vitamin D. From recent
      animal studies, it has been suggested that parathyroid hormone related peptide
      (PTH-rp) may also play a role in perinatal calcium homeostasis.

PMID- 8522723
TI  - Resting energy expenditure of patients with gynecologic malignancies.
AB  - OBJECTIVE: To evaluate resting energy expenditure compared to predicted energy
      expenditure in patients with cervical or ovarian carcinoma who require
      specialized nutritional support. DESIGN: Women with biopsy-proven cervical or
      ovarian carcinoma referred to the Nutrition Support Service were studied. Resting
      energy expenditure was measured by indirect calorimetry and compared to predicted
      energy expenditure (PEE) as determined by the Harris-Benedict equation for
      females. RESULTS: Sixty one patients were studied. Patients with ovarian cancer
      (n = 31) had a significantly higher measured resting energy expenditure (% PEE)
      than patients with cervical cancer (109 +/- 18% vs. 98 +/- 16%, p < 0.02,
      respectively). This difference in measured resting energy expenditure between
      groups could not be explained by differences in the extent of disease,
      nutritional status, body temperature, or nutrient intake between groups. A
      greater proportion of patients with ovarian cancer were hypermetabolic (> 110% of
      predicted) in comparison to patients with cervical cancer (55% vs. 13%, p < 0.01,
      respectively). Measured resting energy expenditure varied between 53% and 157% of
      predicted for the entire population. CONCLUSION: Ovarian cancer patients are more
      hypermetabolic than cervical cancer patients. The Harris-Benedict equation for
      females is a unreliable estimate of caloric expenditure in patients with cervical
      or ovarian cancer receiving specialized nutritional support.

PMID- 8522724
TI  - Pulse dexamethasone does not impair growth and body composition of very low birth
      weight infants.
AB  - OBJECTIVE: Evaluation of repeated pulses of dexamethasone (PDEX), given to
      improve cardiopulmonary outcome, on growth of very low birth weight (VLBW, < 1500
      g) infants. METHODS: In this prospective, double-blind, randomized clinical
      trial, VLBW infants mechanically ventilated at 1 week of age received intravenous
      PDEX or saline placebo (P) for 3 days, every 10 days, until no supplemental
      oxygen or ventilation was required or 36 weeks postmenstrual age (PMA). Weight
      gain, fluid intake, caloric intake, and serum glucose were monitored throughout
      the study. Nutritional assessment at 36 weeks PMA consisted of weight, length,
      head circumference, skinfold thickness measures, body composition by total body
      electrical conductance, and bone mineral content (BMC) by single beam photon
      absorptiometry. RESULTS: 37 PDEX and 31 P infants survived at least 36 days and
      completed the protocol. Average daily weight gain, fluid intake and caloric
      intake were not different between groups. The pattern of weight gain (g/kg/day,
      mean +/- SD) was different: PDEX infants showed significant growth delay during
      (3.0 +/- 11.4) and immediately after (7.8 +/- 8.7) each pulse, with subsequent
      growth acceleration (18.3 +/- 8.2) until the next steroid pulse. In contrast,
      growth rate of P infants was constant (12.6 +/- 3.7) (p = 0.04). Hyperglycemia
      requiring insulin therapy occurred only in the PDEX group (10/37). The catch-up
      growth noted between pulses in the PDEX group was explained only in part by
      insulin therapy. At 36 weeks PMA, there were no differences between groups in
      body size, composition, or BMC. CONCLUSION: PDEX negatively affected glucose
      metabolism and growth patterns during and immediately after drug exposure.
      However, assessment near term gestational age showed similar body composition and
      size in both groups.

PMID- 8522725
TI  - Iron and zinc status of young women aged 14 to 19 years consuming vegetarian and
      omnivorous diets.
AB  - OBJECTIVE: To assess the iron and zinc status of young females, aged 14 to 19
      years, consuming vegetarian and omnivorous diets. METHODS: Dietary intakes (via 3
      day weighed food records), BMI, and laboratory indices of iron and zinc status
      were compared in a convenience sample of 79 lacto-ovo-vegetarians (LOV), 16 semi
      vegetarians (SV), and 29 omnivorous (OM) females. RESULTS: Twenty-nine percent
      LOV, 44% SV, and 17% OM had low iron stores (i.e., plasma ferritin < 12
      micrograms/L); only 3% had anemia. As well, 24% LOV, 33% SV, and 18% OM had serum
      zinc < 10.71 mumol/L and 14% LOV, 14% SV, and 17% OM had hair zinc < 1.68
      mumol/g. Intakes of iron and ascorbic acid from the weighed food records were
      associated with serum iron (p < 0.04) and total iron binding capacity
      (negatively; p < 0.02), respectively, whereas Phy:Zn molar ratios were associated
      with serum zinc (negatively; p < 0.04). Z-scores for BMI were associated with
      serum zinc (p < 0.02) and diet type (p < 0.001); serum AP activity was associated
      with age (p < 0.0001) and oral contraceptive use (p < 0.04). CONCLUSIONS:
      Suboptimal iron and zinc status was attributed to low intakes of poorly available
      iron and zinc in all dietary groups.

PMID- 8522726
TI  - Metabolic alterations of zinc and prostaglandins in both human and animal colonic
      tumor cells.
AB  - OBJECTIVE: To understand the relationship between zinc and prostaglandin (PG)
      metabolisms in inducing colon cancer incidence in human and animals. METHODS:
      Human colonic tumor and normal cells were obtained from Departments of Surgery
      and Pathology at the Kaiser Permanente Medical Center, Los Angeles, CA and US VA
      Medical Center, North Hills, CA. Rat colonic tumor and normal cells were isolated
      from the rats that received two injections of 50 mg/kg of Azoxymethan (AOM) in 2
      weeks and then kept 30 weeks in the animal facility. Then, the effects of zinc on
      the PGE2 synthesis and PGE2 on zinc metabolism in tumor and normal cells were
      determined. RESULTS: PGE2 concentrations in both human and AOM-induced rat
      colonic tumor cells increased compared to those in adjacent normal colonocytes,
      whereas PGF2 alpha concentrations did not change. Gene expression of inducible
      form of prostaglandin synthase (PGS-2) is stimulated in rat colonocytes by
      epidermal growth factor and by tetradecanoyl 13-phorbol acetate (a tumor promoter
      and mitogen) only in the presence of zinc. PGE2 binding activity of rat
      enterocytes was maximum at 15 microM of zinc (normal plasma zinc concentration),
      but PGE2 synthesis activity increased for the first 15 minutes when extracellular
      zinc concentrations were either higher or lower than the normal extracellular
      zinc concentration. However, variations in extracellular zinc concentrations did
      not change the rate of PGF2 alpha synthesis in the normal rat enterocytes. PGE2
      significantly increased zinc uptake rates of colonic tumor cells but PGF2 alpha
      showed only moderate effect. CONCLUSIONS: These results suggest that zinc is
      required for PGS-2 gene expression, that maintaining an optimal zinc nutriture is
      important for normal PG synthesis of intestinal cells, and that only PGE2
      synthesis mechanisms rather than PGS-2 gene expression are altered in colonic
      tumor cells resulting in the abnormal zinc nutriture of these cells.

PMID- 8522727
TI  - Choline deficiency and methotrexate treatment induces marked but reversible
      changes in hepatic folate concentrations, serum homocysteine and DNA methylation
      rates in rats.
AB  - OBJECTIVE: The study compared the effects of feeding rats a choline deficient
      (CD) diet or injecting low doses of methotrexate (MTX) on hepatic folate
      concentration and distribution, homocysteine (Hcy) concentration and DNA
      methylation. METHODS: Thirty rats were divided into three groups and were fed
      either a choline sufficient (CS) or deficient diet (CD), or injected with low
      doses of MTX (0.1 mg/kg/day) for 2 weeks. Half the animals of each group were
      sacrificed and the remaining CD and MTX animals were fed repletion diets without
      methotrexate administration for two additional weeks. RESULTS: CD or MTX resulted
      in a significantly lower folate concentrations (25-50%) compared to the control
      group. Folate distribution in the treated animals was associated with elongation
      of the glutamate chains: higher proportion of hexa (from 14%, control, to 35%,
      choline, p < 0.05), hepta (from 5% to 16%, p < 0.05), and appearance of
      octaglutamyl folates. MTX administration resulted in a similar pattern of hepatic
      folate distribution. Two weeks following the MTX administration and the
      restoration of an adequate choline diet for 2 weeks restored the hepatic folate
      levels to the control animals. CONCLUSIONS: Results are discussed based on the
      possibility that CD and MTX treatment appear to impair the capacity of tissues to
      incorporate folate in only 2 weeks and affect other biomarkers of one-carbon
      metabolism such as Hcy concentration and DNA methylation. This adverse picture
      was partially reversed in a relative short time by simply feeding an adequate CS
      diet and discontinuing MTX injections.

PMID- 8522728
TI  - Skeletal muscle intracellular ionized magnesium measured by 31P-NMR spectroscopy
      across the menstrual cycle.
AB  - OBJECTIVE: The hormonal regulation of magnesium (Mg) metabolism is poorly
      understood. Preliminary evidence suggests that reproductive hormones may
      influence Mg concentrations in various tissues. The purpose of this study was to
      determine if Mg concentrations in blood and muscle are affected by the phase of
      the menstrual cycle. METHODS: Magnesium measures were obtained from 16 women over
      the course of one complete menstrual cycle. The principal outcome measure was
      intracellular ionized Mg ([Mg++]i) in skeletal muscle as measured by 31P nuclear
      magnetic resonance spectroscopy. Three blood measures (serum, red blood cell, and
      mononuclear blood cell) of total Mg ([Mg]) were also obtained. RESULTS: Mean Mg
      concentrations were stable across the menstrual cycle with no evidence of a
      menstrual cycle phase effect for any of the measures. Furthermore, skeletal
      muscle [Mg++]i was not correlated with any blood measure of [Mg]. CONCLUSION:
      These results suggest that physiologic fluctuations in reproductive hormones do
      not influence either blood [Mg] or skeletal muscle [Mg++]i in healthy, regularly
      cycling women.

PMID- 8522729
TI  - Rapid reduction of serum cholesterol and blood pressure by a twelve-day, very low
      fat, strictly vegetarian diet.
AB  - OBJECTIVE: This study was conducted to demonstrate the effectiveness of a
      strictly vegetarian, very low-fat diet on cardiac risk factor modification.
      METHODS: Five hundred men and women, participants in an intensive 12-day live-in
      program, were studied. The program focused on dietary modification, moderate
      exercise, and stress management at a hospital-based health-center. RESULTS:
      During this short time period, cardiac risk factors improved: there was an
      average reduction of total serum cholesterol of 11% (p < 0.001), of blood
      pressure of 6% (p < 0.001) and a weight loss of 2.5 kg for men and 1 kg for
      women. Serum triglycerides did not increase except for two subgroups: females age
      > or = 65 years with serum cholesterol < 6.5 mmol/L and for females 50 to 64
      years with baseline serum cholesterol between 5.2-6.5 mmol/L. High-density
      lipoprotein cholesterol measured on 66 subjects decreased by 19%. CONCLUSION: A
      strict, very low-fat vegetarian diet free from all animal products combined with
      lifestyle changes that include exercise and weight loss is an effective way to
      lower serum cholesterol and blood pressure.

PMID- 8522730
TI  - Use of conventional and SI units.

PMID- 8522731
TI  - Organophosphate insecticide degradation by non-amended and cupric ion-amended
      Fenton's reagent in aqueous solution.
AB  - Improper treatment and disposal of pesticide-contaminated wastewaters raise
      concerns for soil and water contamination. Based on the pilot studies described
      here, chemical treatment via Fenton's reagent (ferrous ion plus hydrogen
      peroxide) of three organophosphorus insecticides in aqueous solution appears
      promising. Results show that the Fenton dark reaction degrades methyl parathion,
      malathion, and methamidophos, and in many cases their breakdown products as well.
      Addition of cupric ion greatly accelerates insecticide disappearance. To maximize
      degradation, further studies of the influence of 1) pesticide structure, 2)
      reagent ratios, and 3) breakdown product competition on reaction rates are
      necessary.

PMID- 8522732
TI  - Neurologic features of chronic minamata disease (organic mercury poisoning) and
      incidence of complications with aging.
AB  - To elucidate the neurologic features of chronic Minamata disease, and the
      incidence of complications with aging, we studied 80 patients with documented
      Minamata disease (organic mercury poisoning) from 1986 to 1994 (mean age: 63
      years). Of the cardinal neurologic findings, sensory impairment was seen with
      highest frequency in 98.8% of patients limited to the extremities in 86.3%.
      Impairment of lower extremity coordination was observed in 60%, constriction of
      the visual field in 51.9%, and retrocochlear hearing loss in 41%. To assess age
      related complications, patients were separated into three groups by age: Group I
      (10 to 39 years); Group II (40 to 69 years); Group III (> or = 70 years). The
      incidences of hypertension and cerebrovascular diseases, organic ophthalmologic
      disorders (including cataracts), presbyacusis, and cervical spondylosis deformans
      increased significantly with age. Compared with a preceding survey (1981 to 1985,
      171 patients, mean age: 63.5 years), the incidences of complicated hypertension
      and cataracts had decreased, whereas those of cerebrovascular disease and
      retinitis pigmentosa remained unchanged. The incidences of abnormal brain
      computed tomography (CT), presbyacusis, cervical spondylosis deformans, and
      positive tests for urine sugar also increased. The incidences of these
      complications other than retinitis pigmentosa were similar to those in the
      general population. These results accurately reflect the recent epidemiological
      disease tendencies in Japan toward a decreased incidence of hypertension and an
      increased incidence of diabetes.

PMID- 8522733
TI  - Nitrogen and phosphorus removal for swine wastewater by ammonium crystallization
      and intermittent aeration process.
AB  - A process on crystallized precipitation of ammonium by adding magnesium salt and
      phosphate was carried out to improve C/N ratio in swine wastewater. After
      completion of crystallized precipitation of ammonium, an intermittent aeration
      process with aeration and nonaeration periods alternated at interval of 1:1 hr
      day-1 is used for the improved swine wastewater (T-N/BOD = 0.14: BOD = 8200
      mg/liter and T-N = 1166 mg/liter). The results obtained from the experiment show
      that the removal ratios of T-N and NH4-N are 91% and 99%, respectively. T-P is
      not removed, while the removal ratio of PO4-P is 60% as 3% of CaCl2 liquid is
      added. The results also indicate that dilution with water is effective to improve
      the removal of phosphorus even if raw swine wastewater contains high
      concentrations of T-N, T-P, BOD, and TOC.

PMID- 8522734
TI  - The microcirculatory effects of peripheral sympathectomy.
AB  - Microvascular physiology following peripheral artery sympathectomy was evaluated
      in seven hands with refractory pain (n = 7) and ulceration (n = 7) by serial
      isolated cold stress testing, which measures digital temperature and cutaneous
      perfusion (laser Doppler fluxmetry). All patients (n = 6) had vasospasm
      (secondary Raynaud's phenomenon) and arteriographically proven digital and palmar
      occlusive disease. Microcirculatory flow responses were correlated with symptoms
      and signs (including ulcer healing) before and after (2-8 weeks, 12-15 weeks, and
      24 weeks) peripheral sympathectomy. Baseline data were compared with those of
      controls (n = 7 extremities). Following surgery, all seven hands had diminished
      pain; six had ulcer healing and one had ulcer reduction. Isolated cold stress
      testing demonstrated abnormalities in temperature and laser Doppler fluxmetry
      response between patients and controls. Although total flow (reflected by
      temperature) was not significantly increased after surgery, peripheral
      sympathectomy increased nutritional flow in these patients with combined
      vasospastic vessels and occlusive injury. The clinical changes observed following
      peripheral sympathectomy appear to be related to postsurgical correction of
      abnormal arteriovenous shunting and to improved nutritional blood flow to
      ischemic areas. This accounts for the resultant diminution of pain and healing of
      ulcers observed in these patients after surgery.

PMID- 8522735
TI  - Vasoactive effects of smoking as mediated through nicotinic stimulation of
      sympathetic nerve fibers.
AB  - Patients who smoke have higher complication rates than nonsmokers following many
      surgical procedures. It is not known if the adverse effects of smoking are caused
      by a nicotine effect or by some other potentially harmful agents that exist in
      tobacco smoke. It is also not known if these vasoactive effects are mediated
      through sympathetic nerve fibers (via nicotinic receptors in ganglia) or through
      elevated circulating levels of vasoactive hormones. We designed a 5-day protocol
      to measure relative blood flow both before and after a digital sympathetic block
      in the digits of subjects who were regular smokers following both smoking and
      wearing of a transdermal nicotine patch. Suitable pulse/wave tracings were
      recorded on 23 subjects. We also measured serum levels of nicotine, cotinine,
      vasopressin, norepinephrine, epinephrine, dopamine, and carboxyhemoglobin on each
      test day. Data for these serum levels were available in 30 test subjects. Digital
      sympathetic block had a significant beneficial effect in reversing the decreased
      digital blood flow that occurred after smoking (and also with use of the nicotine
      patch), despite the elevated circulating levels of vasopressin and norepinephrine
      seen with smoking. The vasoactive effects of smoking are probably due to the
      nicotinic effects on sympathetic fibers at the ganglionic levels.

PMID- 8522736
TI  - Use of the 3M precise microvascular anastomotic system in hand surgery.
AB  - The results of a two-center clinical study on the use of the 3M Precise
      Microvascular Anastomotic System in microvascular procedures for hand trauma are
      presented. Since November 1992, 17 patients (age range, 18-76 years) have
      received an end-to-end vascular anastomosis using this device. All patients had
      vascular trauma or amputation requiring replantation or revascularization
      procedures. The diameter of the anastomosed vessels varied between 1 and 2 mm.
      Sixteen of the 17 anastomoses were at the level of or distal to the superficial
      arterial arch of the hand, with 5 anastomoses as distal as the distal
      interphalangeal joints. No early thromboses were observed in the postoperative
      period, and all operations were successful with regard to tissue survival and
      wound healing. Patency and quality of the blood flow at the site of repair were
      evaluated by means of Doppler ultrasound investigations. In a few cases,
      angiography was used to confirm patency of the device.

PMID- 8522737
TI  - Thumb reconstruction with extended twisted toe flap.
AB  - Twelve amputated thumbs were reconstructed with a neurovascular cutaneous flap
      from the great toe and an osteotendinous flap from the second toe. Both transfers
      were dependent on a single vascular pedicle. One of the 12 reconstructions
      failed. In the remaining 11, the mobility of the metacarpophalangeal joint ranged
      from 10 degrees to 50 degrees, and that of the interphalangeal joint from 10
      degrees to 30 degrees. Opposition and key pinch were restored, and the shape and
      volume were similar to those of the normal thumb. Likewise, the great toe was
      preserved, and all patients had a normal gait. This technique preserves the
      epiphyses for future growth in children and maintains the aesthetic appearance of
      the foot, but it has the disadvantage of involving a lengthy surgical procedure
      with a 17% rate of major complications.

PMID- 8522738
TI  - Flexor carpi ulnaris transfer for radial nerve palsy: functional testing of long
      term results.
AB  - Controversy persists over the use of the flexor carpi ulnaris for transfer to the
      extensor digitorum communis in the treatment of radial nerve palsy. Six patients
      with complete, irreparable radial nerve palsies were treated in part with the
      flexor carpi ulnaris to extensor digitorum communis tendon transfer (standard
      transfers: pronator teres to extensor carpi radialis brevis, flexor carpi ulnaris
      to extensor digitorum communis, and palmaris longus to the rerouted extensor
      pollicis longus) and were functionally tested for long-term results. The average
      follow-up time was 8 years (range, 3-15). A control group was comprised of 10
      volunteers of similar demographics. This study evaluates the long-term functional
      recovery in three categories: range of motion, dynamic power of wrist motion, and
      functional ability as determined by work simulation techniques. The activities
      simulated were swinging a hammer, sawing wood, tightening screws, and using
      pliers. A functional range of motion was maintained in all patients, and the
      power of wrist motion was sufficient to perform all activities of daily living.
      The work simulation testing revealed no significant difference between the tendon
      transfer patients and control group with respect to hand dominance and normal
      variance. All patients were able to perform the simulated work with the same
      variance in power as the control group. Despite the obvious anatomic loss, wrist
      function is not significantly impaired after flexor carpi ulnaris tendon transfer
      for radial nerve palsy.

PMID- 8522739
TI  - Modified Steindler procedure for elbow flexion restoration.
AB  - The results of modified Steindler procedures for elbow flexion performed during
      the past 20 years were reviewed retrospectively. The modifications were designed
      to avoid the phenomenon of the patient having to make a fist in order to obtain
      elbow flexion (Steindler's effect). The flexor carpi ulnaris, the flexor carpi
      radialis, and the palmaris longus, along with a bone fragment, are transferred to
      the anterior aspect of the humerus. The muscles are carefully separated from the
      flexor digitorum superficialis, which is left in place. This avoids both flexion
      of the fingers and pronation. Indications are discussed, especially in brachial
      plexus reconstructive surgery. Steindler's procedure is indicated in upper plexus
      lesions (C5-C6); other transfers are more appropriate for lower plexus palsies.
      Results were assessed according to elbow flexion against resistance. Flexion over
      120 degrees when lifting 3 kg was rated very good. Of 32 modified Steindler
      procedures reviewed, 18 were rated very good, 8 good, 4 fair, and 2 poor.

PMID- 8522740
TI  - Steindler and pectoralis major flexorplasty: a comparative analysis.
AB  - Previously published studies on transfers to restore elbow flexion have rarely
      compared the outcomes among different techniques. We found no comparison between
      the Steindler procedure and pectoralis major tendon transfer. This study compared
      functional outcomes after these two types of elbow flexorplasty performed in
      conjunction with shoulder arthrodesis for patients with brachial plexus injuries.
      The same examiner assessed 14 patients who underwent shoulder fusion and elbow
      flexorplasty. Five had a pectoralis major tendon transfer, and nine underwent a
      modified Steindler procedure. All patients had brachial plexus lesions that were
      irreparable or had not responded to neurolysis, repair, or grafting. Average
      follow-up time was 60 months (range, 12 months-10 years). All patients completed
      a questionnaire (pain, function) and underwent an objective assessment of range
      of motion, isometric strength, isotonic power, grip, and pinch strength. The BTE
      Work Simulator (Baltimore Therapeutic Equipment, Hanover, MD) was used for muscle
      strength testing. Improvement was noted in daily activities including dressing
      and bilateral activities and was reflected in a significant improvement over
      preoperative function. No differences (at p = .05 level of significance) were
      found in objective tests between the pectoralis major transfer and the Steindler
      groups. In the patient requiring stabilization of the shoulder and flexorplasty,
      the pectoralis major tendon transfer was at least equivalent to the modified
      Steindler flexorplasty in terms of range of motion, strength, and subjective
      measures.

PMID- 8522741
TI  - Analysis of carpal instability: I. Description of the scheme.
AB  - There is a lack of a generally agreed analysis of carpal instability that can
      assist in the diagnosis, give guidelines for treatment, and ensure unity when
      reporting results of treatment. Based on the literature and using six categories
      describing chronicity, constancy, etiology, location, direction, and pattern of
      the instability, we present a proposal for a standardized analysis. Using this
      analysis, an instability should be presented with information in all six
      categories. The analysis may be expanded and developed according to future needs.

PMID- 8522742
TI  - Analysis of carpal instability: II. Clinical applications.
AB  - An analytic scheme for carpal instability patterns has been described to help
      standardize reporting of these conditions. Six categories to be recognized in
      each case are chronicity, constancy, etiology, location, direction, and pattern.
      Examples are presented to illustrate the use of this scheme.

PMID- 8522743
TI  - Post-traumatic irreducible nondissociative carpal instability: a case report.
AB  - We present a case that is unusual in two respects. To our knowledge, it is the
      first clearly documented instance in the literature of a post-traumatic,
      irreducible nondissociative volar intercalated carpal instability to result from
      a known wrist flexion force and a known dorsal capsuloligamentous tear. Second,
      the same wrist revealed a coalition at both intraosseous levels of the proximal
      carpal row: a synfibrosis at the scapholunate joint and a synostosis at the
      lunotriquetral joint. Treatment by open removal of an interposed
      capsuloligamentous flap from the radiocarpal joint, followed by alignment of
      carpal elements, temporary internal fixation, and repair of the damaged dorsal
      capsule and ligaments gave an excellent result.

PMID- 8522744
TI  - Percutaneous A1 pulley release: a cadaveric study.
AB  - Percutaneous A1 pulley release was performed on 17 fresh-frozen cadaveric hands
      with a 14-gauge angiocath needle. Each hand was then explored to assess the
      adequacy of release and the degree of injury to adjacent structures. Complete
      release of the A1 pulley was obtained in 45 of the 66 fingers and in 10 of the 17
      thumbs. Significant injury to the flexor tendons was observed in two digits. All
      tendon injuries occurred along the line of the fibers. There were no digital
      nerve injuries. The release was within 2 mm of a thumb digital nerve in seven
      hands and the little finger ulnar digital nerve in two. In the thumb, the close
      proximity of the digital nerves makes percutaneous trigger digit release
      potentially hazardous. With the little finger held in abduction the risk of
      digital nerve injury or inadequate release is reduced. Percutaneous trigger
      finger release can be safely performed in the index, long, and ring fingers.

PMID- 8522745
TI  - Treatment of trigger finger in patients with diabetes mellitus.
AB  - We present a retrospective study of 54 diabetic patients with 121 trigger digits
      treated over a 3-year period by one to three injections of corticosteroid mixed
      with local anesthetic. As a group, diabetic patients responded less favorably to
      treatment by steroid injection (50% symptom resolution) when compared to reported
      outcomes of steroid injection treatment for stenosing tenosynovitis in the
      general population. Insulin-dependent diabetic patients have a higher incidence
      of multiple digit involvement (59% of patients) and of requiring surgical release
      for relief of symptoms (56% of digits) when compared to non-insulin-dependent
      diabetic patients (28% of patients with multiple digit involvement; 28% of digits
      requiring surgery).

PMID- 8522746
TI  - Long-term results following digital flexor tenosynovectomy in rheumatoid
      arthritis.
AB  - A retrospective review of flexor tenosynovectomy for rheumatoid flexor
      tenosynovitis in the palm and digit was performed. Fifteen patients (61 fingers)
      were reviewed for at least 1 year (average, 4 years) after surgery. An average of
      2.2 cm improvement in active flexion (pulp to distal palmar crease) was observed.
      A significant difference in preoperative and postoperative results was found.
      Sixty-seven percent of digits were classified as having excellent or good
      results, 21% fair results, and 12% poor results. The clinical recurrence rate was
      31% and the reoperation rate was 15%. Only minimal complications from the
      extended surgical approach were observed. Debulking the fibro-osseous canal by
      excising a slip of flexor digitorum superficialis was associated with a reduction
      in the recurrence and reoperation rates.

PMID- 8522747
TI  - Effect of partial laceration on the structural properties of the canine FDP
      tendon: an in vitro study.
AB  - The appropriate management of partially lacerated digital flexor tendons in zone
      2 is controversial. Tenorrhaphy has been advocated by some on the basis of
      improving tendon gliding function, whereas others have recommended foregoing
      tenorrhaphy because of the negative impact of repair on the tensile strength of
      the tendon. In light of this division, we undertook a study of the effect of
      varying degrees of partial laceration on the structural properties of the canine
      flexor digitorum profundus tendon. Lacerations up to 90% of the tendon cross
      sectional area were surgically fashioned. We conclude that the structural
      properties of the tendon are increasingly adversely affected as laceration size
      increases. However, based on previous estimates of in vivo forces, even tendons
      with up to 60% cross-sectional area involvement may be strong enough to withstand
      an early active mobilization regimen. Further, we conclude that neither calipers
      nor naked-eye estimates provide a reliable means of assessing the extent of
      tendon laceration.

PMID- 8522748
TI  - Comparative mechanical analysis of dorsal versus palmar placement of core suture
      for flexor tendon repairs.
AB  - This study was designed to evaluate the effect of core suture placement in the
      coronal plane on the tensile strength of flexor tendon repairs. We compared the
      tensile strength of modified Kessler core sutures placed in the palmar versus the
      dorsal side of matched-lacerated human cadaver flexor digitorum profundus tendons
      tested in vitro under static loading. We also compared the relative strengths of
      the dorsal and palmar portions of the flexor digitorum tendons. The mean failure
      load of a dorsal-side modified Kessler suture was 26.5% greater than that of a
      palmar-side modified Kessler suture. The mean strength of the dorsal half of the
      flexor digitorum tendons was 58.3% greater than that of the palmar half of the
      flexor digitorum tendons. Our data demonstrate that the dorsal tendon can sustain
      greater loads-to-failure than the palmar tendon. This suggests that there are
      biomechanical advantages to dorsal as opposed to palmar placement of the core
      suture in clinical tendon repair.

PMID- 8522749
TI  - Intramedullary nailing of proximal phalangeal fractures.
AB  - A retrospective review of 25 consecutive patients with 28 proximal phalangeal
      fractures was performed. Fractures of the thumb were excluded. Twenty-five
      fractures were closed and three were open. All fractures were reduced, closed,
      and fixed using flexible intramedullary fixation with 0.8-mm prebent nails.
      Fractures amenable to flexible intramedullary fixation include short oblique and
      transverse fractures. Contraindications include long oblique, spiral, and
      bicortical comminuted fractures. The average follow-up time was 10 months (range,
      2-20). Five patients with six fractures were lost to follow-up evaluation. All of
      the remaining 23 fractures healed and there were no infections. An average of 2
      degrees angulation was seen on anteroposterior x-ray films. One patient showed 4
      degrees of angulation on the lateral x-ray film. No shortening was noted. One
      fracture showed appreciable malrotation of 10 degrees. Flexible intramedullary
      rodding of specific proximal phalangeal fractures provides excellent results with
      a low complication rate. Proper selection of fractures and good surgical
      technique are necessary to avoid complications.

PMID- 8522750
TI  - Upper extremity function after wrist arthrodesis.
AB  - Several studies have examined the normal range of wrist motion used to accomplish
      activities of daily living. Little information is present, however, on what
      functional limitations might be experienced by patients actually undergoing
      formal wrist arthrodesis. This study undertook comprehensive functional
      evaluation of 23 patients who underwent wrist arthrodesis for post-traumatic
      conditions. Follow-up evaluation averaged 54 months and consisted of a clinical
      questionnaire, the Jebsen Hand Function Test, and a functional rating devised by
      Buck-Gramcko/Lohmann. Fifteen of the 23 patients returned to their original jobs,
      and all patients noted that although the vast majority of tasks could still be
      performed, these tasks were undertaken in a modified fashion. The most difficult
      daily tasks for patients with a wrist arthrodesis to perform involved perineal
      care and manipulating the hand in tight spaces. The Jebsen Hand Function Test
      demonstrated a 64% task completion rate with the fused wrist compared to a 78%
      task completion rate for the normal wrist. The Buck-Gramcko/Lohmann evaluations
      demonstrated an average score of 8.3 out of a possible 10. Patients who have
      undergone wrist arthrodesis can accomplish most activities of daily living and
      other functional requirements, although some adaptation to accomplish these tasks
      is required.

PMID- 8522751
TI  - Iliac crest bone grafting and Herbert screw fixation of nonunions of the scaphoid
      with avascular proximal poles.
AB  - Between 1989 and 1991, 137 nonunions of the scaphoid were treated by the senior
      author, who noted that 26 of these nonunions had an avascular proximal pole (no
      punctate bleeding from the bone at the time of surgery). All 26 nonunions were
      treated with iliac crest bone grafting and Herbert screw fixation. Of these 26
      patients, 17 were followed for more than 1 year after their surgery (average
      follow-up period, 31 months). The average time from injury to surgery was 31
      months. Of the 17 patients included in this study, 12 were treated with a palmar
      approach to the nonunion, 5 with a dorsal approach. The 12 nonunions that
      occurred at either a midwaist or distal location were approached through a palmar
      modified Russe incision and treated with interpositional corticocancellous iliac
      crest bone graft in addition to the Herbert bone screw. The five nonunions with a
      very small proximal fragment were approached through a dorsal incision and
      treated with cancellous iliac crest bone graft and Herbert screw fixation. All
      patients were immobilized after operation in a short-arm thumb spica cast for 3
      months and were then allowed active range of motion of their wrists. Return to
      full activity was permitted once preoperative wrist motion was restored.
      Radiographic union, as defined as bridging trabeculae of bone present in all x
      ray films, occurred in nine patients, an incomplete union or persistent fibrous
      union in seven, and a nonunion in one patient. Using the scaphoid outcome score,
      an assessment scale based on pain, occupation, wrist motion, strength, and
      patient satisfaction, functional results were graded as excellent in six
      patients, good in five patients, fair in four patients, and poor in two patients.
      The average range of motion of the wrist did not significantly improve after
      surgery, but the average grip strength of the injured hand increased by 29 lbs.
      There were no intraoperative complications. However, three patients required
      further operative procedures including radial styloidectomy, pin removal, and
      carpal tunnel release. No patient has required either a proximal row carpectomy
      or wrist arthrodesis. Previously published results of avascular proximal pole
      scaphoid nonunions suggest that union cannot be obtained and functional results
      are uniformly poor. In contrast, the functional and x-ray results of our patients
      are markedly improved over these previous studies--emphasizing the importance of
      iliac crest bone grafting, rigid internal fixation, and appropriate postoperative
      immobilization.

PMID- 8522752
TI  - Analysis of finger extensor mechanism strains.
AB  - Strains in the extensor mechanism of the finger were measured in a cadaver model
      using Hall-effect transducers. Several components of the mechanism were evaluated
      at different joint positions, with different intrinsic and extrinsic tendon
      loading conditions, and after creating a boutonniere deformity. Landsmeer's
      theory that predictable and obligatory interactions occur within the extensor
      mechanism during finger movement is strongly supported by our results. The
      concept of the Bunnell intrinsic-tightness test was confirmed. Results were
      consistent with clinical observations and current theories on the pathomechanics
      of claw and boutonniere deformities. Based on our experimental findings, we
      conclude that strain analysis is an effective method of evaluation of the
      extensor mechanism with potential for in vivo surgical applications.

PMID- 8522753
TI  - Tendon graft reconstruction of extensor hood deficits with subluxation.

PMID- 8522754
TI  - The extensor tendons to the little finger: an anatomic study.
AB  - Fifty cadaver hands were dissected to better delineate the extensor tendon
      anatomy to the little finger. The extensor digitorum communis was present in 35.
      Of 15 hands without an extensor digitorum communis, 12 had a junctura present.
      Three hands lacked both extensor digitorum communis and juncturae. Transfer of
      the extensor digiti minimi tendon in these hands could cause loss of extension to
      the little finger. Ten hands had a direct attachment of the extensor digiti
      minimi tendon on the abductor tubercle. Twenty-two hands had either an attachment
      of the extensor digiti minimi on the abductor tubercle, an unbalanced ulnar slip
      of the extensor digiti minimi, or both, anatomic factors that could--in the event
      of ulnar nerve compression or laceration--cause Wartenberg's sign. Twenty-eight
      hands did not have an anatomic variant of the extensor that could cause ulnar
      deviation of the little finger.

PMID- 8522755
TI  - Evaluation of carpal canal pressure in carpal tunnel syndrome.
AB  - Preoperative electrophysiologic testing and intraoperative carpal canal pressure
      measurements were performed on 957 hands in 647 patients with clinical signs of
      carpal tunnel syndrome. Fifty-five symptomatic hands in 48 patients were normal
      in both distal sensory latency and distal motor latency preoperatively. Carpal
      canal pressure was, however, significantly elevated compared to control data in
      all 55 hands. After complete subcutaneous release of the carpal canal using the
      Universal Subcutaneous Endoscope system, carpal canal pressure was reduced to
      within the normal control range. Clinical symptoms of carpal tunnel syndrome
      improved in all 55 hands. Postoperative electrophysiologic data remained within
      normal range in patients who agreed to receive electrophysiologic examinations.

PMID- 8522756
TI  - In vivo measurement of carpal tunnel pressure in the functioning hand.
AB  - We recorded directly the pressure within the carpal tunnel during nine different
      functional positions of the hand and wrist in 102 hands of 92 subjects. Carpal
      tunnel syndrome was present in 81 hands, and 21 served as controls. A significant
      rise in pressure was recorded not only with wrist flexion but also with wrist
      extension, making a fist, holding objects, and isolated isometric flexion of a
      finger against resistance. Intratunnel pressure dropped after 1 minute of hand
      and wrist exercises and remained below the resting pressure for over 15 minutes
      of continuous measurement. We did not observe a rebound phenomenon. Clinical
      Application: Non-surgical treatment of carpal tunnel syndrome should also include
      a significant reduction in making a fist, holding objects, pushing, and isolated
      finger work such as key punching and typing. Activities that require sustained
      contracture of finger flexor muscles (eg, grasp and hold) also should be avoided.
      Brief intermittent wrist and hand exercise is recommended to reduce the
      intratunnel pressure.

PMID- 8522757
TI  - Anatomic investigation of the role of the lumbrical muscles in carpal tunnel
      syndrome.
AB  - This study investigates whether the proximal origins of the lumbrical muscles
      contribute significantly to the etiology of carpal tunnel syndrome. We explored
      the carpal canals of 128 hands in patients undergoing carpal tunnel release for
      carpal tunnel syndrome. The origins of the lumbrical muscles were examined at the
      time of surgery and their relation to the transverse carpal ligament was recorded
      in all cases. Also, 40 cadaveric hands were dissected to determine the lumbrical
      muscle origins. In the hands of patients with idiopathic carpal tunnel syndrome,
      the lumbrical muscle origins were located significantly more proximal in the
      canal than were the muscles in the cadaveric hands. Younger patients whose jobs
      required repetitive hand motions had large lumbrical muscles and origins that
      were more proximal than the lumbricals found in the hands of fresh cadavers.

PMID- 8522758
TI  - Median nerve compression at the wrist due to intracarpal canal sepsis.

PMID- 8522759
TI  - Management of finger ulcers in scleroderma.
AB  - Twelve patients (15 hands) with documented scleroderma and chronic nonhealing
      digital ulcers were followed for their response to nonoperative and operative
      treatment. The patients were initially managed with nifedipine, biofeedback,
      digital xylocaine blockade, and silver sulfadiazine topical ointment and
      cessation of all vasoconstrictive agents. Ulcerations healed in 6 of 15 hands and
      remained healed at a 2-year follow-up examination. The remaining nine hands in
      seven patients failed nonoperative treatment and underwent a palmar digital
      sympathectomy. These chronic digital ulcerations healed within 6 weeks after
      surgery. After a 26- to 64-month follow-up period, six of the nine hands remained
      free of all digital ulcerations. Two patients (three hands) had partial
      recurrence of the ulceration. Digital sympathectomy can be an effective procedure
      for treating nonhealing digital ulcers in scleroderma patients after nonoperative
      treatment has failed. Significant vaso-occlusive disease is likely to be present
      in these patients, as demonstrated by arteriography. Our initial approach is
      cessation of all vasoconstricting agents, nifedipine biofeedback, and local
      antibiotic ointment. Wrist blocks with xylocaine and marcaine are offered if
      these modalities fail. If these methods do not result in healing of the ulcer
      within 12 weeks, then digital sympathectomy is considered.

PMID- 8522761
TI  - The Mitek Mini G2 suture anchor: biomechanical analysis of use in the hand.
AB  - We inserted 36 Mitek Mini G2 suture anchors (Mitek Surgical Products, Westwood,
      MA) into various sites of 14 fresh cadaver hands. A single-strand 0-Ethibond
      suture (Ethicon, Sommerville, NJ) was threaded through each anchor, inserted into
      bone, and loaded to failure. In all cases, either the anchor pulled out (11 of
      36) or the suture broke (25 of 36). No anchors fractured. We also measured the
      breaking strength of six types of suture material (without anchors) commonly used
      by hand surgeons; all failed at much lower loads than those generated in our
      anchor pullout model. We conclude that the Mitek Mini G2 suture anchor possesses
      sufficient pullout strength for tendon and ligament fixation in the hand,
      including the distal phalanx.

PMID- 8522760
TI  - Desmoplastic melanoma of the hand: case reports and review of the literature.

PMID- 8522762
TI  - Allergic reactivity and IgG subclasses to a proteinase fraction of Setaria
      digitata in filariasis.
AB  - A low molecular weight fraction (30 KDa) of the cattle filarial parasite Setaria
      digitata that was earlier demonstrated to have allergenic activity was
      characterized to be a zinc-dependent cysteine proteinase. Immediate type
      hypersensitivity (ITH) reaction to the proteinase was evaluated in lymphatic
      filariasis patients and in endemic controls from Orissa, India. The extent of ITH
      positivity to the proteinase in infected individuals ranged from 20% in chronic
      filariasis (CP) patients group to 56% in asymptomatic microfilaraemic carriers
      (AS). About 62% of endemic normals (EN) were also ITH positive. The serum levels
      of IgG subclasses were compared in ITH positive and ITH negative filarial
      patients (AS and CP) as well as in endemic normals (EN) respectively. IgG4 levels
      were found to be inversely dependent on ITH reaction only in AS groups.
      Asymptomatic patients (AS) with positive ITH reactivity had lower IgG4 than ITH
      negative individuals from the same group. The serum levels of other IgG
      subclasses except IgG2, did not correlate with ITH reactivity. IgG2 levels were
      higher in ITH negative EN and CP patients but not in the AS group.

PMID- 8522763
TI  - Effect of mercury on the immune response and mean intensity of Ascaris suum
      infection in guinea pigs.
AB  - The subchronic effect of mercury on selected immunological parameters was studied
      in guinea pigs with experimental Ascaris suum infection. HgC1(2) given for 28
      days reduced significantly T- and B-cell populations in the lymphoid organs and
      the phagocytic ability of peritoneal macrophages. The subsequent infection of
      HgC1(2)-intoxicated animals elevated the studied immunological parameters, but in
      comparison with infected non-intoxicated guinea pigs they remained significantly
      suppressed. The mercury compound in infection stressed animals caused a slight
      alteration of the complement CH50 and AH50 activity. The specific circulating
      antibody level in infected and HgC1(2) treated animals rose a little by day 12
      p.i. and then again decreased significantly, compared with untreated guinea pigs.
      The mean intensity of infection with migrating Ascaris larvae in HgC1(2)-treated
      animals increased by 15%, compared with controls.

PMID- 8522764
TI  - Cytochemical localization of cytochrome c oxidase activity in mitochondria in the
      tegument and tegumental and parenchymal cells of the trematodes Echinostoma
      trivolvis, Zygocotyle lunata, Schistosoma mansoni, Fasciola gigantica and
      Paragonimus ohirai.
AB  - Cytochrome c oxidase in the mitochondria of the tegument and tegumental and
      parenchymal cells was examined cytochemically in Echinostoma trivolvis,
      Zygocotyle lunata, Schistosoma mansoni, Fasciola gigantica and Paragonimus
      ohirai, trematodes that inhabit different sites in their vertebrate hosts. Clear
      differences in enzyme activity occurred in the mitochondria of these species,
      probably reflecting the different energy metabolisms of these worms. Marked
      aerobic metabolism occurred in S. mansoni and P. ohirai adults that inhabit the
      host mesenteric veins and the lungs, respectively. The tegument and parenchymal
      cells of S. mansoni possess relatively few, small mitochondria with tabular
      cristae which are heavily reactive for cytochrome c oxidase. In P. ohirai, the
      activity for cytochrome c oxidase in tegumental mitochondria increased gradually
      from juveniles to adults, reflecting that the respiratory activity increased with
      growth and the aerobic metabolism is activated when the worms reach the lung. P.
      ohirai juveniles and adults had two types of mitochondria with different shapes
      and enzyme activities that were located in two different types of parenchymal
      cells. The intestinal species, E. trivolvis had mitochondria in the basal aspect
      of the tegument, and some variations in enzyme activity of their mitochondria in
      the tegumental and parenchymal cells were observed, suggesting that they possess
      both aerobic and anaerobic metabolic systems. Z. lunata that live in rodent caeca
      are devoid of mitochondria in the tegument and have many characteristic
      mitochondria with undeveloped cristae in the parenchymal cells. Mitochondria of
      F. gigantica showed weak or no activity for cytochrome c oxidase, suggesting that
      the worm is well-adapted to an anaerobic environment in the host bile duct.

PMID- 8522765
TI  - Effects of free and liposomized praziquantel on worm burden and antibody response
      in mice infected with Mesocestoides corti tetrathyridia.
AB  - The parasite burden in the liver and peritoneal cavity, and antibody levels
      directed to whole worm extract, have been monitored in serum from ICR-strain
      mice, infected orally with 55 tetrathyridia of Mesocestoides corti (Cestoda,
      Cyclophyllidea). The subcurative does (3x or 6x) of praziquantel (PZQ) (10 mg.kg
      1 body weight) were administered to mice from day 14 post infection (p.i.) in two
      drug formulations: as PZQ suspended in Dorfman vehicle, or as PZQ incorporated in
      liposomes (lip.PZQ). The appearance of antibodies was time-dependent and
      correlated with the rate of reduction in numbers of tetrathyridia. PZQ in three
      and six doses caused the highest fall of parasite numbers in the liver on day 1
      post therapy (p.t.). In the peritoneal cavity, a similar reduction in worm burden
      occurred but only after six doses of the drug. The worm count in the peritoneal
      cavity from groups of mice injected with lip.PZQ decreased most markedly on day 7
      p.t., in the group treated with six doses of the drug. In the liver, the highest
      larvicidal effect, compared with the controls, was observed 6 days later (i.e.
      day 13 p.t.), following three doses of lip.PZQ. In all treated groups, two peak
      values of antitetrathyridial antibody levels were detected between days 1 and 13
      p.t. (i.e. days 17 to 29 p.i.), after which there was a gradual but continuous
      increase in antibody tire.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522766
TI  - Population biology of Pomphorhynchus laevis in brown trout from two lakes in the
      west of Ireland.
AB  - Since Ireland is the only country in which Pomphorhynchus laevis (Acanthocephala)
      uses brown trout (Salmo trutta) as its preferred definitive host, the population
      biology of the parasite in this host was investigated thus enabling a comparison
      to be made with data collected on P. laevis from other hosts, particularly the
      cyprinids, chub and barbel. Over a period of 12 months, 549 brown trout were
      caught from two lakes, Lough Feeagh and Bunaveela Lake, in the Burrishoole River
      system, Co. Mayo, Ireland. The parasite component community was dominated by a
      single species, P. laevis. Fifty eight percent of the trout sample were infected
      with the acanthocephalan and the mean abundance (+/- SD) was 3.1 +/- 5.1 The
      relationships between the prevalence and abundance of P. laevis and season and
      site of host capture and host age and sex were explored. As single factors one of
      these parameters emerged as significant contributions to changes in parasite
      abundance although some interaction terms proved to the significant. A random
      sample of over 700 P. laevis parasites were subjected to further investigation
      and their size, position in the intestine and maturity status are described.
      Parasites attained an average weight of 7 mg and occupied the posteriad positions
      within the fish intestine (77%). Parasites from this sample of Irish brown trout
      attained a similar average size to those found in chub and barbel from England.
      42.3% of the total parasites examined contained ovarian balls only and 17%
      contained fully mature acanthors. Therefore only a moderate proportion of female
      worms contained mature acanthors in these trout whereas the majority of worms
      recovered from a sample of chub were gravid. Utilizing a logistic regression
      model, parasite size, season, and site of host capture emerged as particularly
      significant factors which contribute to whether a parasite contains mature eggs.

PMID- 8522767
TI  - Metazoan parasite community structure in brown trout from two lakes in western
      Ireland.
AB  - A total of 549 brown trout were caught from two lakes, Lough Feeagh and Bunaveela
      Lake, in the Burrishoole system, Co. Mayo, Ireland. Seven species of metazoan
      parasite were detected but only four species occurred in > or = 10% of the
      sample. The parasite community of the trout was dominated by a single species,
      Pomphorhynchus laevis, with a prevalence if 58%. Only one allogenic helminth
      species was recorded from the trout, Diphyllobothrium ditremum, with the
      community mainly comprising autogenic species. Few differences were found between
      the two lakes, although the larger lake, Lough Feeagh, did contain some trout
      which harboured more parasite species and had, on average, fish with higher
      numbers of individual parasites. Measures of species richness and diversity were
      very low, indicating an impoverished helminth community with little potential for
      interspecific interactions. Host age was found to significantly influence these
      indices of infracommunity structure.

PMID- 8522768
TI  - The genetic relationships between Echinostoma caproni, E. paraensei, and E.
      trivolvis as determined by electrophoresis.
AB  - Adults of Echinostoma caproni, E. paraensei, and E. trivolvis were processed for
      starchgel electrophoresis. Ten enzyme systems representing 12 structural loci
      were examined using three different buffer systems. E. paraensei and E. caproni
      were found to be genetically inbred as indicated by the lack of heterozygosity in
      individual worms. All three taxa showed fixed differences indicating they are
      distinct species. Fixed differences were found between E. paraensei and E.
      caproni in six enzyme systems, between E. paraensei and E. trivolvis in five
      enzyme systems, and between E. trivolvis and E. caproni in five enzyme systems.
      Phenic relationships among the three species showed E. caproni was genetically
      more similar to E. trivolvis than to E. paraensei.

PMID- 8522769
TI  - Ultrastructural study of Trichinella spiralis with emphasis on adult female
      reproductive organs.
AB  - The ultrastructure of the reproductive organs of adult female T. spiralis was
      described on the basis of extensive observation under an electron microscope. The
      organisms were recovered from the host intestine 7 days after oral infection. The
      organs consisted of a single ovary, seminal receptacle, uterus and vagina,
      confirming the reports described by previous authors at light microscopical
      level. All the organs were surrounded by a basal lamina and epithelial cells, and
      were bathed in haemolymph. Ova were formed in a germinal zone on the ovary wall
      exhibiting a half-moon shape, and spread to other sides of the ovary. Mature ova
      exhibited a smooth cell surface, cuboidal shape, prominent cytoplasmic polysomes,
      a clear nucleus and a well-developed nucleolus. Embryos in early stage of
      development consisted of numerous small cells and were surrounded by a sheath. As
      they matured they shed the sheath and left a pool of sheaths in the uterus.
      During oogenesis and embryogenesis of adult worms in normal development, three
      occurred lipid droplets and the degradation of embryos; reportedly signs of worm
      damage.

PMID- 8522770
TI  - Distribution of cobalt in parasitic helminths.
AB  - The distribution of cobalt in parasitic helminths belonging to the trematodes,
      cestodes or nematodes was determined by the use of an atomic absorption
      spectrophotometer. The results of these analyses have demonstrated that growing
      trematodes (smaller forms) with active oogenesis and spermatogenesis contained
      more cobalt that older forms (large or very old adults) with empty uteri and
      large lobulated testes. In cestodes the neck region of cysticerci and immature
      proglottids of adults showed more cobalt than the cyst portion of cysticerci and
      hydatid or mature and gravid proglottids of worms. Similarly, the youngest
      endogenous daughter cysts of Echinococcus granulosus showed more cobalt in their
      walls than those of larger forms. The element was found more concentrated in
      nematode eggs than in adult females, irrespective of species of host.

PMID- 8522771
TI  - A comparison of Echinostoma trivolvis and E. caproni using random amplified
      polymorphic DNA analysis.
AB  - The random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR)
      technique was applied to two closely-related echinostome species, Echinostoma
      trivolvis and E. caproni, demonstrate interspecific polymorphisms of genomic DNA.
      Band patterns generated using five individual primers showed that these two
      echinostomes were genetically distinct, although they share genomic DNA to some
      extent.

PMID- 8522772
TI  - Note on the first occurrence of larval Echinococcus multilocularis in
      Clethrionomys rex in Hokkaido, Japan.
AB  - Larval Echinococcus multilocularis was found in Clethrionomys rex in Hokkaido,
      Japan. C. rex is a new host record for E. multilocularis. The cysts were filled
      with numerous protoscoleces suggesting a potential role of this vole in a natural
      cycle of transmission.

PMID- 8522773
TI  - Susceptibility of HIV to inactivation by disinfectants and ultraviolet light.
AB  - Assays were developed to assess a variety of conditions and presentations of
      infectious HIV to potential inactivating sources. A range of commercially
      available disinfectants with active constituents including glutaraldehyde,
      chlorine, phenolics, alcohol, iodine and quaternary ammonium compounds was
      tested. In addition, u.v. light was investigated as a potential inactivating
      source. All products were assessed against cell-free HIV in culture medium and
      cell-associated HIV suspended in medium or whole human blood. All products
      completely inactivated cell-free HIV following a 1 min exposure. However, cell
      associated HIV was more resilient, requiring exposure of 5 min or more for some
      disinfectants. The effectiveness of the disinfectants was further compromised in
      the presence of blood.

PMID- 8522774
TI  - An audit programme for central venous catheter-associated infections.
AB  - Central venous catheters (CVC) are commonly associated with both localized and
      systemic infection. This paper describes an audit programme which was designed to
      review clinical practice associated with the insertion and subsequent care of CVC
      and their possible relationship to the development of infection. The programme
      was produced by a joint working group of the Hospital Infection Society and the
      Research Unit of the Royal College of Physicians and is subdivided into an audit
      of hospital practices and patient management associated with the use of CVC. It
      consists of a number of questions designed to evaluate all areas of CVC use,
      including the assessment of the incidence of associated local and systemic
      infection. Use of the questionnaire should allow policies for CVC insertion and
      care to be reviewed thereby, facilitating improvements, which may in turn reduce
      the incidence of infection associated with CVC.

PMID- 8522775
TI  - Nosocomial enterococci: resistance to heat and sodium hypochlorite.
AB  - Six strains each of Enterococcus faecium and E. faecalis were investigated with
      respect to their resistance to heat and sodium hypochlorite. All enterococci
      survived the temperatures and holding times specified by the Department of Health
      (DoH) for the disinfection of 'foul and used' or 'infected' linen (65 degrees C
      for 10 min or 71 degrees C for 3 min). In addition, three strains (one E. faecium
      and two E. faecalis) could withstand 150 ppm available chlorine for 5 min, the
      treatment suggested by the DoH for the disinfection of heat labile materials.
      Further, our results showed that four strains of E. faecium were able to survive
      the British Standard for heat disinfection of bedpans (80 degrees C for 1 min).
      The significance of these findings with particular reference to the potential for
      enterococci to survive and disseminate in the hospital environment is discussed.

PMID- 8522776
TI  - Infection resistance of surface modified catheters with either short-lived or
      prolonged activity.
AB  - It has been suggested that the invasion of microbes into the catheter tract
      occurs mainly at the time of catheter insertion. To investigate whether the
      presence of an antimicrobial environment during the initial period after
      insertion is sufficient to reduce the risk of subsequent catheter colonization
      and infection, we evaluated the use of benzalkonium chloride-heparin bonded (BZK
      hep) central venous catheters, which exhibit short-lived surface antimicrobial
      activity, using a rat subcutaneous model. Bacterial adherence on these catheters
      was determined, seven days after challenging the insertion site with 10(6) cfu of
      Staphylococcus aureus. A chlorhexidine-silver sulphadiazine impregnated catheter
      (Arrowg+ard), with longer lasting surface antimicrobial activity, and a
      hydrophilic coated catheter ('Hydrocath'), were evaluated simultaneously for
      comparison. Unlike Arrowg+ard antiseptic catheters, BZK-hep 'Hydrocath' and
      control catheters had significant bacterial adherence on their surface.
      Arrowg+ard catheters were colonized in 19% of the animals compared with 100% in
      all the other groups (P < 0.05; mean cfu cm-2: control = 1.3 x 10(6), BZK-hep =
      4.3 x 10(5), Hydrocath = 2 x 10(5), Arrowg+ard = 71). Our results indicate that
      catheters with short-lived surface antimicrobial activity are unlikely to provide
      long-term protection against catheter-related infection. The efficacy of
      Arrowg+ard catheters may be due to the initial high rate of kill and prolonged
      antimicrobial activity.

PMID- 8522777
TI  - Oral ciprofloxacin as prophylaxis in gastroduodenal surgery.
AB  - One hundred and fifty patients undergoing gastroduodenal surgery were randomly
      allocated to receive intravenous (iv) cefuroxime, iv ciprofloxacin or oral
      ciprofloxacin as prophylaxis. There were no differences in the incidence of
      postoperative infection complications or duration of stay among the three groups.
      Oral ciprofloxacin offers obvious advantages in terms of ease of administration
      and cost.

PMID- 8522778
TI  - The origin of coagulase-negative staphylococci isolated from blood cultures.
AB  - The source of coagulase-negative staphylococci (CNS) isolated from blood cultures
      and thought to be contaminants was investigated over a two month period. Isolates
      recovered from swabs taken from patients, doctors and laboratory staff were
      compared with the blood culture patient isolate in an attempt to identify the
      source of contamination. Six hundred and ninety-six blood culture sets were
      received of which 28 were contaminated with CNS. Nineteen of these blood cultures
      had sufficient data to be included in this study. Six were matched to isolates
      from the patient's skin and none to the medical or laboratory staff. Major
      differences in the antibiograms were seen between the patients, medical and
      laboratory staff. Organisms from patients and medical staff were more likely to
      have multiple antibiotic resistances. It appears that the most important source
      of CNS contamination of blood cultures processed in a semi-automated manner is
      the patient's own skin flora.

PMID- 8522779
TI  - An outbreak of campylobacter food poisoning in a health care setting.
AB  - An outbreak of campylobacter food poisoning in a group of health care workers is
      reported. The outbreak involved 12 of 31 staff members attending a departmental
      party. Investigations revealed that a chicken dish was the most likely vehicle of
      infection. The relative risk of developing symptoms after eating this dish was
      6.15 (P < 0.002). Further investigation established that not only had the cooking
      instructions been misunderstood but storage of the the food the morning of the
      party did not comply with Department of Health guidelines. The outbreak was
      associated with considerable morbidity and cost. It is important that health care
      workers other than professional catering staff are aware of the guidelines
      available to ensure the correct preparation and storage of food if such events
      are to be held in hospital departments. It is also important that manufacturers
      of chicken products ensure that labelling regarding further cooking is clear and
      in large print.

PMID- 8522780
TI  - Surgical wound infections due to Propionibacterium acnes: a study of 10 cases.
AB  - Ten cases of surgical wound infection in which Propionibacterium acnes was
      probably the aetiologic agent were reviewed; in five the organism was isolated in
      pure culture. Six patients underwent a neurosurgical procedure. The average time
      for development of infection was 17.5 days (range 1-30 days). All patients were
      cured by surgical drainage and, in nine cases, with appropriate antimicrobial
      therapy. In conclusion, P. acnes must be considered as a cause of surgical wound
      infections especially after neurosurgery.

PMID- 8522781
TI  - Problems in the management of penicillin-resistant pneumococci.

PMID- 8522782
TI  - Diagnostic value of Clostridium difficile cytotoxin assay.

PMID- 8522783
TI  - Comparison of the mycobactericidal activity of 2% alkaline glutaraldehyde and 'Nu
      Cidex' (0.35% peracetic acid)

PMID- 8522784
TI  - Behavioral effects and body activity level in female hospital staff nurses during
      work hour.
AB  - To examine if there are changes in the levels of affections over different times
      of day, affective state measures, alertness, irritability, mental tension,
      headache and anxiety of 100 female staff nurses were assessed, on visual analogue
      scales at 2-h intervals over a 24-h work cycle spread over three different shift
      works. Oral temperature was also recorded simultaneously. Sleep pattern, dietary
      habit and menstruation cycle of subjects were monitored. Analysis of variance
      reflected a significant rise in oral temperature as the day progressed with a
      peak during 16:00-18:00 h, which however gradually declined thereafter.
      Significant changes in the affective states indicated ascendancy in alertness,
      mental tension and anxiety within the first few hours of the beginning of each
      shift work, but descendancy towards the end of it. Further studies on some more
      affective states and physiological measures which may show parallelism have been
      suggested.

PMID- 8522785
TI  - Introducing ergonomics through "subak" organization among the farmers in Bali.
AB  - Due to a shortage of owned land, it is impossible for Balinese farmers to adopt
      fully mechanized tools or techniques. Therefore, the use of handtools for
      agricultural work is still the only alternative. The ergonomical evaluation of
      local farmers' handtools is becoming so important. An intensive study was
      conducted in Bongan Village of Tabanan. The study was focused on the agricultural
      work cycle and the handtools used. The observation technique was completed by
      interview and measurement. The results are as follows: 1) all farmers in Bongan
      village are members of "subak" (water organization group); 2) any activity
      regarding agricultural work must be in accordance with what has been set forth by
      the "subak"; 3) the handtools used are hoe, plough, sickle, long knife, herb
      cleaner and local thresher; 4) pattern of crop planted per year are paddy-paddy
      crop; 5) some improvements on handtools used have been done, but some are still
      not ergonomically sound. To anticipate the result No. 5, ergonomics intervention
      have been done, such as awareness program, informal workshop and showing good
      examples of ergonomics tools. From the immediate results, it could be concluded
      that farmers in Bongan Village are well responsive to the ergonomics information
      and its advantages.

PMID- 8522786
TI  - Experiences of successful action programmes for occupational health, safety, and
      ergonomics promotion in small scale enterprises in Thailand.
AB  - Small-scale enterprises are playing a vital role for the national economy in
      Thailand, creating employment in both urban and rural areas. The improvement of
      working conditions and occupational safety and health, together with improved
      productivity has long been a priority. How we could practically provide owners
      and workers of small-scale enterprises with opportunities for improvement action
      has been our concern. In the present project, we have adopted a new programme of
      action which emphasizes participation, a positive approach and locally made
      solutions. The project site was in Samutprakarn province, an industrial zone near
      Bangkok. Four local small-scale enterprises participated in the action programme.
      They were a lead smelting, a dry-cell battery plant, a wet-cell battery plant and
      a pesticides factory. The programme consisted of the following steps. 1) A
      demonstration training session was conducted to motivate the enterprises'
      representatives to take action. Locally invented improvement examples were
      presented and small group discussion was organized for facilitating their action.
      2) The participants were encouraged to use a checklist for assessing safety,
      health and ergonomic risks in their own workplaces. Concrete action plans were
      established based on their checklist results. 3) The improvement action started,
      in which step-by-step approaches were emphasized. Advisory and supporting roles
      of expert teams comprising the authors and other professionals were important to
      accelerate and sustain the action at these enterprises. On the basis of this self
      help action, the participants were enabled to make many improvements at their
      workplaces. These improvements developed by their own initiative were multi
      factorial. They included 1) machine and electrical safety device, 2) workstation
      redesign, 3) materials handling improvement, 4) establishing new welfare
      facilities such as canteens or bathrooms and 5) work environment improvement such
      as better lighting or enclosure of hazardous substances. Our experiences showed
      that there was a large potential to initiate local improvement actions and
      duplicate them in a participatory manner. Of particular importance were the
      positive attitudes towards self-help workplace action and the focus on locally
      available solutions.

PMID- 8522787
TI  - Ergonomics productivity enhancement at government-owned sugar cane factories in
      east Java, Indonesia.
AB  - To cope, both with the increasing demand for sugar and to win the global
      competition as well, government-owned sugar cane limited number xxi-xxii, has
      decided to enhance its productivity, among other things, by implementing
      ergonomics principles within their factories. In the execution, ergonomics
      application have been carried out since 1992, which resulted in safer, healthier,
      and more efficient working conditions and environment. Some of the improvements
      yielded economic gains through higher productivity via increased output, lower
      cost, faster processing, etc. Improvements related to cane transloading and
      unloading processes resulted in a higher amount of cane being transferred from
      the trucks to the lorries as well as from the lorries to the cane table. Fewer
      clinical visits, lower health care costs, more efficient inspection, and fewer
      fatigue complaints are also achieved by improvement steps, which increase the
      productivity as end results. With all those economic gains, full and long lasting
      management's concern and commitment could be created without a doubt.

PMID- 8522788
TI  - Ergonomics for industrially developing countries: an alternative approach.
AB  - The main focus of ergonomics is the improvement of working conditions and safety.
      Studies of workers in industrialized countries (ICs) have focused on subjects
      like occupational health, work physiology, biomechanics, design, and cognition.
      However, in industrially developing countries (IDCs), the characteristics and
      conditions of the worker and his workplace are different. This paper suggests an
      alternative approach to improve working conditions for ergonomists in
      industrially developing countries. Together with the ergonomic factors previously
      stated, this approach also considers the broader social and cultural context
      within which the worker and his workplace exist. The operator is regarded as a
      product of his socio-cultural environment. His work place (e.g. its ambience,
      organization, shopfloor conditions, and the state of technology) and his work
      practices (e.g. attitudes, behavior, ethics, and problem-solving abilities) are
      affected by societal conditions (like quality of training and education,
      technical infrastructure, and technical culture).

PMID- 8522789
TI  - How to benefit from ergonomic interventions through participation by workers,
      managers and the company: an example of a small- to medium-sized factory with no
      ergonomic knowledge.
AB  - Many of the managers, and supervisors in small- and medium-sized businesses are
      technicians. These are workers with many years of experience in one specialized
      technical area. They know, in their minds, what should be improved, and how, in
      order to make the work easier to do. However, their knowledge of work improvement
      techniques, and how to think together with the workers, and further how to best
      lead their troops, is nil. This report focuses on managers and supervisors who
      had never even heard the word "ergonomics," and touches on cases of successful
      implementation of ergonomic work improvements. The subject work-places are part
      of an automobile parts manufacturing plant operating under a typical production
      system of small amounts of many product types: cutting process machinery
      workshop, press workshop and packing and distribution workshop. At the stage when
      they became aware of ergonomics, the key words for improvement which they
      mentioned were "manual lifting" and "working posture." As a result of various
      observations, analysis techniques and meetings, they introduced a push car with
      lifters as support equipment. However, the most significant result was that they
      were able to convince the company's owner of its contribution to productivity
      improvement, using objective data. Also, with regard to the push car
      manufacturer, they designed the specifications for the push car themselves and
      participated in its production. Of course, they were also praised by the workers
      for achieving a work method involving no strain or waste.

PMID- 8522790
TI  - Relation between feelings of fatigue, reaction time and work productivity.
AB  - Taking into consideration the limited amount of research that has been done
      focussing on fatigue among workers in Indonesia, the writer has taken it upon
      herself to investigate the indicators of chronic fatigue of the concrete block
      and sewer pipe cast workers of a place located in Sleman District of Yogyakarta.
      The purpose of this study was to prepare an instrument to evaluate the feelings
      of fatique; to know the relationship between feelings of fatigue measure and
      reaction time measure on work productivity, to know the relationship between
      feelings of fatigue measure and reaction time measure. 1) KAUPK2 were prepared to
      evaluate the feelings of fatigue in chronically fatigued Indonesian workers. 2)
      There is a significant correlation between feelings of fatigue measure and work
      productivity, and between reaction time measure and work productivity as well. 3)
      There is no significant correlation between feelings of fatigue measure and
      reaction time measure. 4) There is a significant difference between both work
      productivities. The mean decrease in work productivity relative to reaction time
      is smaller than relative to the feeling of fatigue. 5) This investigation also
      clarified other kinds of relationships such as that between feelings of fatigue
      and work productivity between workers less than 25 years old and those more than
      that age. Based on the regression analysis, there was no significant correlation
      between reaction time and work productivity at the age of less than 25 years, but
      there was a significant correlation between feelings of fatigue and productivity.
      For workers 25 years old or older, the result is the reverse.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8522791
TI  - Industrial pollution and quality of life of workers in Bangladesh.
AB  - The present study was designed to investigate the effects of industrial pollution
      on the quality of life of workers in Bangladesh. A total of 110 workers
      comprising 60 from a polluted industry and 50 from a non-polluted industry were
      randomly selected for this study. The measuring instruments used were: The
      Inventory of Subjective Health (Dirken, 1967), The General Health Questionnaire
      (Goldberg, 1972), The Occupational Stress Index (Srivastava and Singh, 1981), The
      Life Descriptive Scale (Wright, 1988), and the Interview Schedule on Personal and
      Health Related Questionnaire (Khaleque, 1988). The results showed that the
      workers of the polluted industry suffered more from health problems and were less
      satisfied with their quality of life than those of the non-polluted industry. The
      results also revealed that the workers' health, well-being and quality of life
      were also affected by unhygienic home environment, malnutrition, transport
      problems, and lack of health care facilities. The result supported the view that
      the workplace pollution and the health and well-being of the workers were
      negatively related to each other.

PMID- 8522792
TI  - Effects of wearing two different clothing ensembles on endurance performance of
      handgrip exercise.
AB  - The experiment was done to investigate the effects of wearing two different
      clothing ensembles on endurance performance of handgrip exercise in 7 female
      subjects. Subjects walked on the ground for 1 h where air temperature ranged from
      21 to 25 degrees C, glove temperature from 22 to 28 degrees C, relative humidity
      from 30 to 50% RH, air movement from 0.3 to 0.90 m/s, wearing the clothing
      ensemble HALF or LONG. The clothing ensemble HALF consisted of half-sleeved
      shirts, knee-length trousers, sandals, hat and LONG of long-sleeved shirts, long
      trousers, gloves, socks, walking shoes, hat. After 1 h of walking, the subjects
      exercised with a hand ergometer in a climatic chamber (25 +/- 1 degrees C, 50 +/-
      10% RH) until volitional exhaustion. Rectal temperature, heart rate, body weight
      loss, number of contractions and strength of each contraction were measured
      during the experiment. Major findings were as follows: 1) Number of contractions
      in handgrip exercise after 1 h of walking was significantly greater in clothing
      ensemble HALF than in LONG, for which lower maintenance of rectal temperature
      during 1 h of walking on the ground in HALF might be responsible. 2) There was no
      significant difference in the strength of contraction between two clothing
      ensembles. Our present results suggest that how to wear clothing is of
      significance for the endurance performance of handgrip exercise.

PMID- 8522793
TI  - Adaptation of the resettled Kenyah Dayak villagers to riverine environment in
      east Kalimantan: a preliminary report.
AB  - The Kenyah Dayak in East Kalimantan (Indonesia), who migrated from their
      mountainous homeland to a riverine village in the 1940s, have subsisted on slash
      and-burn rice cultivation. To cope with rapidly increasing population, the
      villagers have not changed their farming practice to increase land productivity
      but instead have exploited fields in remote riverbanks, using motorized canoes.

PMID- 8522794
TI  - Participatory ergonomics that builds on local solutions.
AB  - Ergonomic interventions must be a local process that responds to the particular
      needs of local people. In view of the many constraints, a special attention is
      drawn to participatory ergonomics as an effective means of finding locally
      workable solutions. Recent experiences show that the best way to utilize its
      practical advantage is to focus on solutions. The practical steps in providing
      necessary support for participatory ergonomics should include (1) a good starting
      point for group discussion and subsequent participatory action based on locally
      achieved examples; (2) prioritizing different elements of the workplace by means
      of checklists of available solutions; and (3) making small improvements with a
      view to learning-by-doing through small wins. Good local examples that have been
      achieved in the given local conditions can show how improvements can be done in
      the local conditions and thus motivate people in making improvements. The next
      important step is to help the participants determine priority solutions by means
      of "action checklists" that list the available solutions. It is necessary to
      concentrate on those aspects in which both better working conditions and higher
      productivity are accessible simultaneously. They include operational, cognitive
      and organizational aspects. Through learning-by-doing, the participants must be
      able to base their judgement on the results of relative assessment of locally
      available solutions and to implement the chosen solutions. To sustain active
      initiatives of the participants, support and advice must be provided which are
      suitable for working in small groups, sharing experiences and identifying
      workable solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522795
TI  - The irruption of new technologies: a new challenge for ergonomics and
      anthropotechnology.
AB  - The irruption of New Technologies in South-East Asia has dreadful social effects
      such as unemployment and the rejection of former worker skills, but is also an
      opportunity to show that ergonomics has resources which have been neglected so
      far in this part of the world. The outstanding feature of these resources, which
      are vital for the successful transfer of these New Technologies, is that they are
      both technically and economically indispensable. Although the well-being, health
      and safety of workers may be sadly overlooked without drastic economic effects,
      this is not the case when using New Technologies, since costly mistakes may arise
      if the operators are unable to use computerized systems properly. Cognitive
      ergonomics associated with situated cognition may then make a great contribution.
      Since New Technologies are generally imported from Europe, the United States or
      Japan, they include special features which originate from these industrialized
      societies. Thanks to Ergonomic Work Analysis, we can discover the difficulties
      encountered in the importing country and find solutions based on
      anthropotechnology concepts, methodologies and knowledge.

PMID- 8522796
TI  - Improvement of lifting heavy objects work.
AB  - In 1993, the Ministry of Labour and Welfare had to make compensation payments to
      11,308 workers (equivalent to 7.22%) for their sickness caused by lifting and
      moving heavy objects. This figure tends to be increasing each year. From survey
      of working conditions, we found that most workers beaned their back in order to
      lift heavy objects repeatedly in each working day. Therefore, it is important to
      educate and train our workers to change their working habits in order to solve
      this problem. This study was conducted within a targeted group of 40 workers,
      aged between 20-30 years, whose duties are to lift soft drink cases. The study
      involved observing the workers' way of performing their work, interviewing them
      regarding the pain in different parts of the body, and testing of their muscle
      strength. We discovered that these workers beaned their back when lifting soft
      drink cases repeatedly and thus experienced moderate to medium levels of back
      pain. Moreover, their muscle strength weakened at the end of each working day. We
      then undertook training courses, educating them and showing them how to do it
      right. The workers have accordingly implemented the new method they have learned
      in performing their daily responsible tasks. Follow-up studies to assess the
      results were made continuously and we were pleased to learn that back pain
      problem has dramatically decreased. A comparison of muscle strength before and
      after work showed that the decrease of back muscle strength was less in the
      experimental group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522797
TI  - Development of mat weaving frame for better posture using ergonomic principles.
AB  - Ergonomic principles were used to build the model of a mat weaving frame in order
      to help workers have better posture. The work level and seat were elevated to a
      proper height, with sloped work area. The study model was accepted because it is
      comfortable and because it reduced back and leg pain. Villagers not only
      participated in building the frame but also showed their potential in model
      development for easier and faster weaving.

PMID- 8522798
TI  - The need for ergonomics considerations for the design and development of
      agricultural machinery in Thailand.
AB  - Agriculture plays an important role in developing countries which are mainly
      located in tropical regions. Agriculture is an industry with tremendous
      opportunities for the application of ergonomics principles. Working conditions
      are extremely difficult due to severe environmental conditions, long working
      hours, strenuous work and the use of mobile equipment. The ignorance of the
      majority of ergonomics principles in the design of agricultural equipment make
      the conditions more difficult. Thailand is one of the important suppliers of
      agricultural products in the world. Mechanization has expanded tremendously
      during the last 10 years and the number of agricultural machinery has rapidly
      increased. This paper looks at ergonomics principles which must be considered in
      the design and development of agricultural machines and equipment used in
      Thailand. It was identified that the common farming system in Thailand is rice
      based cultivation, mostly in swampy conditions with heavy clay soil. It was also
      found that the most energy-consuming task in agriculture was primary cultivation.
      The most widely used machine is a power tiller which is suitable for the farm
      sizes available and can be operated easily. Most of the power tillers and other
      equipment were found to be locally made, with less than 5% imported.
      Unfortunately, there was no standardization in power tiller manufacturing which
      led to increasing farmers' strain. There is still a need to collect more
      ergonomics data of Thai farmers such as anthropometry, strength and physical work
      capacity for the design and development of agricultural machines and equipment
      used in Thailand. Different ergonomic consideration for the design and
      development of agricultural machinery have been suggested.

PMID- 8522799
TI  - An intelligent safety feature for AGV's economic operations: a simulation
      analysis.
AB  - A typical automated guided vehicle (AGV) is equipped with a number of warning and
      safety devices to prevent injury-causing accidents due to its mishap operations.
      Standard safety devices, such as an emergency bumper and a non-contact obstacle
      sensor, sometimes result in uneconomic operations of AGVs since they frequently
      cause stop-and-go situations. This paper discusses the use of a new intelligent
      safety feature which not only provides effective warning for the AGV's approach
      but also helps reduce stop-and-go situations which normally occurred when a
      sensor detects an obstacle. The proposed feature integrates functional operations
      of sensors, warning devices, an onboard microprocessor, and the AGV's driving
      mechanism. Computer simulations of AGV's operations both with and without this
      intelligent safety feature were also performed and their results are compared.

PMID- 8522800
TI  - Eye scanning behavior as a discriminator of instrument- and scenery-centered
      flight task.
AB  - Aircraft pilot's eye scanning behavior represented by saccadic amplitudes and
      dwelling time of eye movements is a promising indicator of discrimination whether
      some flight task is instrument- or scenery-centered. The saccadic amplitude seems
      to reflect spatial and temporal values of target information. The dwelling time
      or gaze duration reflects the changing rate of visual information, amounts
      extracted from and density and complexity of the target information, or
      experience level of a relevant pilot. This study is for confirming the validity
      of the above indicator to discriminate the two types of flight tasks, instrument-
      and scenery-centered tasks. Five jet aircraft pilots, aged 25 to 32, participated
      in this experiment. A flight simulator equipped with a computer generated visual
      scene (field of view: 116 degree (H) x 25 degree (V)) was used. Five kinds of
      flight tasks were selected. These were takeoff, level flight, low-airspeed
      flight, acrobatic flight (minimum timed turn), and landing. These tasks were
      selected with the difference in degree of instrument- or scenery-centered flight,
      by the pilots' comments. Eye movements during simulator flight were recorded by a
      conventional electrooculographic apparatus with an 12-channel polygraph system.
      Analogue data from the amplifiers was digitized at a sampling rate of 2 kHz, and
      stored in a computer system. Horizontal components of eye movements by flight
      task were analyzed. Mean saccadic amplitudes (microV) showed significant
      differences among flight tasks, and no significance between subjects was
      obtained. The largest mean amplitude was in the acrobatic flight, and the
      smallest was in the low-airspeed flight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522801
TI  - Visual comfort in VDT workstation design.
AB  - This study aims to give recommendations for a comfortable visual display terminal
      (VDT) workstation design by investigating physiological resting states of the eye
      in 3 experiments. Dark vergence, in experiment 1, was evaluated to be at a
      distance of about 50 cm from the eye as an average of 14 subjects. Dark vergence
      was found to shift farther with an upward gaze while a nearer shift occurred with
      a downward gaze. In experiment 2, the average dark focus for 11 subjects was
      found to be 1.4 diopters (D) or a distance of about 74 cm from the eye.
      Experiment 3 ascertained the superiority of a positive display polarity (dark
      characters on a bright background) under 500 1x illuminated level, by using pupil
      size analysis in 10 subjects. The ergonomic recommendations for a VDT workstation
      obtained in this study are a positive display polarity under regular lighting
      condition, a downward gaze, and a viewing distance between 50 and 70 cm.

PMID- 8522802
TI  - Pupillary response among VDU users in daylighted workplaces.
AB  - Daylighted workplaces can complicate the viewing of visual display unit (VDU)
      tasks. Incoming direct- and/or reflected-daylight components can distort surface
      luminance distributions in both the direct- and screen-reflected visual fields.
      Pupillary response to these sources moreover may differ significantly, for
      example, between window- and interior-exposures, affecting bilateral depth of
      field and accommodation. Accordingly, it is hypothesized that pupil diameter is a
      valid ergonomic indicator of visual comfort for viewing targets at workplaces
      with varying daylighting exposures. This hypothesis is tested by measuring the
      pupillary response of four VDU users, each while viewing three targets at each of
      six different workplaces in a daylighted room. An iriscorder is used to record
      pupil diameter independently for left and right eyes in response to keyboard,
      screen, and background-surround surface luminances. The significant differences
      in pupil diameter among the three targets at the six positions can be explained
      by the luminance differences rendered by the incoming daylight. On this basis, it
      is further hypothesized that smaller pupil diameters in response to a limited
      range of graduated luminances correspond to more comfortable viewing conditions.
      Provision of these viewing conditions hold implications for VDU workplace layout,
      work organization, and control of electric lighting and cooling loads.

PMID- 8522803
TI  - Improving workplace environments and working conditions at worksites providing
      school lunch service in Japan.
AB  - With the cooperation of All Japan Prefectural and Municipal Workers' Union, we
      have started an overall program on occupational safety and health from 1984. This
      program has several strategies aimed at preventing occupational injuries and work
      related diseases. At first, we analyzed the relationship between work-related
      hazards and occupational factors, and to identify dangerous or hazardous factors
      in the workplace. Second, we have conducted a couple of intervention studies at
      worksites and evaluated these improvements. Third, we discussed the priority,
      feasibility and cost of improvements with Workers' Union members and school lunch
      workers. Fourth, during the last decade, Workers' Union and many researchers have
      demanded that regulations be implemented which would establish comprehensive
      safety and health programs. Fifth, we provided the workers with procedures on how
      to improve working environments and conditions. These education and training
      programs are provided for small-group working ("safety and health circle"), and
      demonstrate to workers their abilities to solve occupational safety and health
      problems and to empower them with respect to health-related issues. Finally, we
      discussed and evaluated the preventive effects of improving workplace
      environments and working conditions. The overall program on occupational safety
      and health at worksites is developing nationwide and is gradually taking effect.

PMID- 8522804
TI  - Cancer profile in Surat and its vicinity.
AB  - A retrospective study of cancer was conducted in the region of South Gujarat
      particularly in Surat and its vicinity over a period of 6 years (1980-85) to
      determine type and frequency of occurrence of various malignancies. During this
      period 2358 new cancer cases were recorded. A total of 60 types of cancer have
      been detected and confirmed histopathologically. Oral, laryngeal and oesophageal
      malignancies were common in males. In females, cancer of breast formed the
      largest group followed by cancer of cervix. A comparative high rate of lung and
      testicular cancers was recorded in males. In females, cancers of ovary, stomach
      and lung were more common. In the present study, the incidence of leukaemias was
      recorded to be low as compared with other types of cancer. Lack of awareness and
      ignorance of the disease, addiction to tobacco and alcohol and increasing
      environmental pollution could be some of the factors responsible for higher
      incidence of cancers.

PMID- 8522805
TI  - Depression in general clinical practice--a diagnostic problem.
AB  - The study was conducted on 100 patients suffering from depression with the aim to
      highlight the common manifestations of depression in people belonging to a
      developing country like India, and to apprise the general practitioners and
      medical specialists of various disciplines, of various manifestations of
      depression to help early detection and timely treatment of the problem. It was
      observed that depression had varied manifestations like depressed mood, anxiety,
      somatic features, insomnia, lack of interest, paranoid ideas, obsessions, etc.
      Although 100% of patients had depressed mood but only 22% actually complained of
      it. Most patients often selectively highlighted somatic manifestations and
      overtly suppressed the mood component, thereby posing a diagnostic problem to the
      physician.

PMID- 8522806
TI  - Clostridium difficile--associated diarrhoeal diseases: an overview.

PMID- 8522807
TI  - Tension pneumocephalus following posterior cranial fossa surgery in sitting
      position.

PMID- 8522808
TI  - Mucinous metastatic adenocarcinoma of spermatic cord.

PMID- 8522809
TI  - Consumer Protection Act and the medical profession.

PMID- 8522810
TI  - Impact of gatt agreement on drug prices.

PMID- 8522811
TI  - Commercialisation of medical education--a review of capitation fee colleges.

PMID- 8522812
TI  - Commercialisation of medical education--a review of capitation fee colleges.

PMID- 8522813
TI  - Oxygen gas cylinder explosion.

PMID- 8522814
TI  - Problems of AIDS in developing countries.

PMID- 8522815
TI  - New problem in diagnosis of kala-azar.

PMID- 8522816
TI  - Medical education and private institutions.

PMID- 8522817
TI  - High fibre diet in diabetes mellitus.

PMID- 8522818
TI  - Revised drug policy.

PMID- 8522819
TI  - Prevention of maternal mortality in eclampsia.

PMID- 8522820
TI  - Clinicopathological study of clinically undiagnosed cases of kala-azar with
      special reference to grading of parasites.
AB  - Clinicopathological study of 34 clinically undiagnosed cases of kala-azar has
      been undertaken with a view to establish the diagnosis and correlate the
      quantitative grading of Leishmania donovani in bone marrow/splenic aspirates with
      clinical features and duration of disease. The ages of the patients were between
      5 and 45 years. The duration of illnesses ranged from 2-24 months with 47% having
      2 months' duration. Splenomegaly was less than 7 cm in 70.5% cases. Anaemia,
      leucopenia and mild thrombocytopenia were present in all the cases. Aldehyde test
      was positive in 47% cases. Bone marrow aspiration revealed the parasites in 82.3%
      cases. L donovani was also observed in 66.6% cases of splenic aspiration
      including 6 cases where bone marrow failed to reveal the parasite. Grading of the
      parasites in bone marrow and splenic aspirates revealed majority of the cases
      (73.5%) were in 3+ and 4+ grades. No correlation between splenic size and
      duration of illness or parasite grading was detected. Neither any positive
      correlation between parasite grading and duration of illness was observed.

PMID- 8522821
TI  - Risk factors and angiographic profile of coronary artery disease in young.
AB  - A total of 124 patients of ischaemic heart disease under 40 years of age (96 with
      myocardial infarction and 28 with angina) were studied for risk factors of
      coronary artery disease. Electrocardiogram, treadmill test, lipid profile and
      coronary arteriography were done in all cases. Smoking (56.4%) and
      hyperlipidaemia (30.6%) emerged as the major risk factors. Further stratification
      of lipid profile revealed that predictive value of hypercholesterolaemia could be
      enhanced by considering the different ratios of lipoproteins and indices of
      atherogenicity. Coronary arteriography revealed a preponderance of single vessel
      disease (48.4%)-left anterior descending being most commonly involved (71.8%).
      Increase in low density lipoprotein fraction was related to multivessel
      involvement.

PMID- 8522822
TI  - Vesicovaginal fistulae: a 12-year study.
AB  - Repairs in 49 cases of vesicovaginal fistulae were performed during the last 12
      years. Obstetric cause for vesicovaginal fistulae was noted in 81.63% cases and
      the most important being obstructed labour (73.46% cases). Repair was successful
      in 71.42% cases. Factors favourable for success were a non-obstetric fistula,
      small size fistula (< 10 mm) and absence of fibrosis. Repair operations were
      performed mainly by vaginal flap technique. The fistulous track was not excised.
      Polyglactin suture gave the best results.

PMID- 8522823
TI  - Morbidity profile of desert population engaged in salt production in Rajasthan.
AB  - A total 2120 salt workers were examined in 8 camps organised at different salt
      sites in Rajasthan. These camps were organised to find out the morbidity
      conditions among salt workers and to provide preventive and curative treatment
      for the ailments. The majority of salt workers who attended the camps were males
      (79.0%) in comparison to females (21.0%). The majority of workers belonged to
      Scheduled Castes followed by Backward Class and Scheduled Tribes at all sites.
      The major morbidity disorders observed during these camps were dermatological,
      respiratory, musculoskeletal, gastro-intestinal and ophthalmological in both the
      sexes. The prevalence of hypertension was 4.3% among both sexes. The morbidity
      pattern in male workers was agreeing among Sujangarh and Kuchaman and after that
      Pokran and Didwana were agreeing with highest rank correlation, whereas in female
      workers it was agreeing among Nawa and Sujangarh and after that Phalodi and
      Pokran were agreeing with highest correlation.

PMID- 8522824
TI  - Towards a safer motherhood.
AB  - One hundred cases each, in induced and spontaneous labour, were analysed to
      compare which group could achieve safer motherhood. It was observed that induced
      group with controlled labour has many maternal and foetal advantages like
      undisturbed domestic arrangements, avoidance of fatigue of patients and her
      relations, short duration of labour and minimal exposure to stress of labour,
      lower incidence of caesarean section and minimised perinatal morbidity and
      mortality.

PMID- 8522825
TI  - Prevalence of cortisol deficiency in late HIV disease.
AB  - In order to determine the prevalence of cortisol deficiency in advanced HIV
      disease and to examine whether it may be predicted by clinical features or
      biochemical abnormalities, we conducted a prospective study which assessed
      responses to a rapid ACTH stimulation test (short-duration synthetic
      corticotrophin test, synacthen test) in HIV-positive patients with a CD4 count of
      < or = 50 x 10(6)/l. Subjective fatigue, postural drop in blood pressure,
      electrolyte changes, presence of concurrent opportunist infection and drug
      treatment were recorded. Cortisol responses were defined as 'normal' (a post
      stimulation cortisol level > or = 450 nmol/l), 'abnormal' (post stimulation
      cortisol level < 350 nmol/l) or 'impaired' (an intermediate response). Of 49
      patients tested (42 male, seven female), a suboptimal response (abnormal or
      impaired) was found in 14 (29%) and frank insufficiency in eight (16%). Cortisol
      deficiency was not predicted by postural drop in blood pressure, biochemistry or
      symptoms of fatigue. Patients with an impaired/abnormal test were not more likely
      to have cytomegalovirus or mycobacterial disease but were more likely to be
      taking megestrol acetate (P = 0.05, Fisher's exact test). Two of three patients
      with initially normal tests developed impaired/abnormal cortisol responses on re
      testing 6-9 months later. Cortisol deficiency is common in late stage HIV
      disease, but symptoms of fatigue and postural hypotension, as well as biochemical
      findings, are poor predictors of cortisol deficiency. We found good subjective
      response to therapy. Routine screening by a rapid ACTH stimulation test is
      recommended in HIV-positive patients with CD4 count < or = 50 x 10(6)/l. Re
      testing at regular intervals may be necessary. The interaction between megestrol
      acetate, cortisol metabolism and synacthen testing requires further
      investigation.

PMID- 8522826
TI  - Epstein-Barr virus (EBV) hypersensitivity of peripheral B lymphocytes in patients
      with EBV genome-positive Burkitt's lymphoma.
AB  - Peripheral blood mononuclear cells (PBMC) from four Japanese patients with
      Epstein-Barr virus (EBV) genome-positive Burkitt's lymphoma (BL) during remission
      were exposed to the B95-8 strain of EBV. Maximum concentrations of the EBV
      determined nuclear antigen (EBNA) before cellular DNA synthesis were similar to
      those of healthy counterparts. Subsequently, EBV-immortalised cell lines were
      established. These immortalised lymphoblastoid cells were treated with 12-O
      tetradecanoylphorbol-13-acetate (TPA) and superinfected with the P3HR-1 strain of
      EBV. EBV early antigens (EA) and viral capsid antigen (VCA) were expressed in
      approximately 3-10 fold higher concentrations by these lymphoblastoid cells than
      by those from patients with other types of malignant neoplasia including EBV
      genome-negative BL and from healthy counterparts. Moderate to extremely high IgG
      antibody titres to EBV VCA as well as IgG antibodies to EA were demonstrated in
      these patients during the study. These results suggest that defective underlying
      cellular mechanisms for regulating the replication of EBV may be present in
      patients with EBV genome-positive BL.

PMID- 8522827
TI  - Cytomegalovirus viraemia in HIV infection: association with intercurrent
      infection.
AB  - The aim of this retrospective study was to investigate the clinical significance
      of cytomegalovirus (CMV) viraemia in HIV-infected subjects (with or without AIDS)
      who had attended this hospital during a 45 month period. They were reviewed
      regularly and, when clinically indicated, tested for CMV viraemia. The blood of
      105 subjects was cultured for CMV and 34 had at least one episode of CMV viraemia
      during the review period. The viraemia was present during CMV disease in nine of
      the 34 positive patients and was the only detectable infection in another two. In
      the remaining 23 patients, CMV viraemia occurred in association with intercurrent
      opportunistic infection. Among these 23 patients, the viraemia resolved in 12
      after treatment (or natural resolution) of the intercurrent infection and only
      one of these 12 developed CMV disease (mean review period: 8 months). In another
      seven patients, CMV viraemia persisted despite treatment (or natural resolution)
      of the intercurrent infection and four subsequently developed CMV disease (mean
      review period: 4 months) (P = 0.08, Fisher's exact test). From the remaining four
      patients, no specimens for CMV culture were obtained after treatment of the
      intercurrent infection. The CD4 count was higher in the 12 patients in whom there
      was resolution of the viraemia [mean CD4 60 x 10(6)/l] compared with the seven in
      whom the viraemia persisted [mean CD4 45 x 10(6)/l]. These findings suggest that
      in some HIV-positive patients, CMV viraemia was potentiated by intercurrent
      infection with another micro-organism and that its treatment was sufficient to
      mitigate the CMV disease.

PMID- 8522828
TI  - P-fimbriation and haemolysin production are the most important virulence factors
      in diabetic patients with Escherichia coli bacteraemia: a multivariate
      statistical analysis of seven bacterial virulence factors.
AB  - Diabetic patients, as compared to non-diabetic subjects, run an increased risk of
      acquiring Gram-negative bacteraemia. We therefore studied the prevalence and
      coexpression of seven bacterial virulence markers of 69 Escherichia coli strains
      isolated from 64 bacteraemic patients with diabetes mellitus and 67 E. coli
      strains from faeces of healthy controls. The strains were analyzed for haemolysin
      (HLY) production, aerobactin-mediated iron uptake (AMI), cytotoxic necrotizing
      factor (CNF) production, expression of cell surface hydrophobicity, P-fimbriae,
      mannose-resistant haemagglutination (MRHA) and mannose-sensitive
      haemagglutination (MSHA). All bacterial properties were significantly more common
      among the bacteraemic strains (P < 0.02 vs. controls). Correlations between HLY
      and CNF (P < 0.0004) and between P-fimbriae and MRHA (P < 0.0001), MSHA (P <
      0.0002) or AMI (P < 0.05), as well as between MRHA and MSHA (P < 0.0005) were
      observed. In patients with proteinuria, as sign of diabetic complications in the
      urinary tract, HLY-negative strains, P-fimbriae-negative strains, and strains
      which were both HLY-/CNF-negative, were more common (P = 0.04, P < 0.01 and P =
      0.048, respectively). Using a multivariate statistical analysis, production of
      HLY and the expression of P-fimbriae were the two virulence factors with the
      highest discrimination between bacteraemic and control strains. In conclusion,
      all virulence factors studied were more prevalent in bacteraemic than in control
      strains, although HLY and P-fimbriae were shown to be of greatest and independent
      importance. Low virulent strains (P-fimbriae-, HLY- and CNF-negative) were more
      prevalent in diabetic patients with signs of renal complications.

PMID- 8522829
TI  - Group A streptococcal bacteraemias in Denmark 1987-89.
AB  - A retrospective study of laboratory-verified cases of Group A Streptococcal
      bacteraemias in Denmark was conducted for the period 1987-1989 after a sudden
      increase occurred during the winter 1988-1989. The aim of the study was to
      describe the epidemiology in the period and to compare cases during the outbreak
      period with cases in a period with a baseline risk. Based on isolates, a total of
      242 cases in 240 patients were included in the study and information on previous
      health of the patients, source of infection (community-acquired or nosocomial)
      and outcome were obtained from hospital records. During the epidemic period the
      total incidence increased three-fold. The frequency of type 1 increased from 1 in
      5 to 1 in 2. The number of previously healthy individuals falling ill with type 1
      increased 25-fold. The relative increase was higher among patients with community
      acquired infection than among patients with nosocomial infection. The lethality
      rate was 48% during the epidemic in which 38% of the cases occurred. As early
      diagnosis and treatment are the two most important measures to prevent serious
      outcome, effectiveness and timeliness of surveillance systems are of extreme
      importance.

PMID- 8522830
TI  - Isolation of atypical mycobacteria from tap water in hospitals and homes: is this
      a possible source of disseminated MAC infection in AIDS patients?
AB  - Infections caused by mycobacteria other than tuberculosis (MOTT), especially
      Mycobacterium avium complex (MAC), are common in AIDS patients, but rare in
      immunocompetent persons. The route of transmission is unknown, but tap water
      could provide a possible source of infection: MAC was isolated from tap water in
      the U.S.A. but this has not been reported in Germany. We therefore investigated
      tap water in Berlin for the presence of mycobacteria and compared radiometric
      (Bactec) and standard plate culture methods processing large volumes of water
      samples. The Bactec method yielded equal results compared to standard methods but
      had the advantage of easy handling. Mycobacteria were isolated from 50/118
      (42.4%) samples and from 21/30 (70%) sites. The most frequently isolated species
      was Mycobacterium gordonae (from 28% samples and from 53.3% sites); MAC was
      isolated from two samples only (1.7%).

PMID- 8522831
TI  - Epidemiology of Vibrio cholerae O139 with special reference to intrafamilial
      transmission in Calcutta.
AB  - A total of 27 families of hospitalised patients (index case families) suffering
      from acute watery diarrhoea caused by Vibrio cholerae O139, and 14 neighbourhood
      families were bacteriologically screened for 4 consecutive days to determine the
      extent of V. cholerae O139 infection amongst healthy contacts and other suspected
      vehicles of transmission at the intrafamilial level. V. cholerae O139 was
      isolated from faeces of 14.6% of healthy contacts in index case families as
      compared to none in neighbourhood families (P = 0.002). The organism could be
      recovered from 3.7% of handwashings of contacts of index cases and also from
      stored drinking water (8.0%), open well water (28.6%), flies (3.8%) and pond
      water (25.0%) used by the index case families and none from neighbourhood
      families. The large number of asymptomatic infected persons indicate an
      epidemiological similarity to that of eltor cholera. The organisms may be carried
      on hands and may act as a potential source of infection to other inmates through
      contamination of stored drinking water, open wells etc. The results will be
      useful in formulating strategies for intervention of transmission of V. cholerae
      O139 at the community level.

PMID- 8522832
TI  - HIV-2 strikes injecting drug users (IDUs) in India.
AB  - Manipur, a north-eastern state of India bordering Myanmar, observed introduction
      of HIV-1 among fairly large number of IDUs in October 1989, followed by rapid
      spread within the next 6 months. HIV-2 in injectors was not present until
      recently, though it was detected from other parts of India in 1991. This
      communication reports for the first time presence of HIV-2 among young injectors
      of Manipur. All the HIV-2 infected IDUs were also found to be infected with HIV
      1. HIV-2 has affected a large number of people in Africa through heterosexual
      transmission. It remains to be seen whether HIV-2 spreads rapidly also among the
      drug-injecting population of Manipur. Observation of the disease progression
      among HIV-2 infected IDUs will also be of interest.

PMID- 8522833
TI  - Microbiology of nosocomial sinusitis in intensive care unit patients.
AB  - We performed a 2-year microbiological study of specimens of sinus fluid recovered
      from patients with suspected nosocomial sinusitis in six intensive care units.
      Over that period, 103 cases of sinusitis were documented by positive culture. The
      number of cases varied widely from one unit to another and was particularly high
      in the neurosurgical unit. Cultures were often polymicrobial. The main pathogens
      were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and
      Enterobacteriaceae. Streptococcus pneumoniae and Haemophilus influenzae were far
      less frequently isolated. Anaerobes and yeasts were often associated with aerobic
      bacteria. The pathogen involved was also recovered from bronchopulmonary samples
      in 50 patients and from blood cultures in seven patients.

PMID- 8522834
TI  - Pasteurella multocida--an uncommon cause of obstetric and gynaecological sepsis.
AB  - Pasteurella multocida is a common cause of wound infection following animal
      inflicted wounds, but is a rare cause of female genito-urinary sepsis. We present
      a case of vulval sepsis and a case of intrapartum septicaemia with this
      bacterium. These two cases indicate that Pasteurella multocida can occasionally
      colonise the female lower genital tract and this bacterium should be considered
      in the differential diagnosis of serious infection related to this site.

PMID- 8522835
TI  - Meningitis due to oral streptococci following percutaneous glycerol rhizotomy of
      the trigeminal ganglion.
AB  - Percutaneous rhizotomy of the trigeminal ganglion is an established technique in
      the management of trigeminal neuralgia. Meningitis has been reported as a
      complication of radiofrequency rhizotomy. We report two cases in which
      percutaneous glycerol injection of the trigeminal ganglion was followed by
      meningitis due to oral streptococci. While initial laboratory features might be
      considered consistent with meningitis due to Streptococcus pneumoniae, optimal
      therapy is likely to differ as a consequence of current antimicrobial
      susceptibility patterns.

PMID- 8522836
TI  - Immunotherapy with Mycobacterium vaccae combined with second line chemotherapy in
      drug-resistant abdominal tuberculosis.

PMID- 8522837
TI  - An atypical case of Corynebacterium diphtheriae endocarditis and subsequent
      outbreak control measures.
AB  - An atypical case of Corynebacterium diphtheriae endocarditis with severe
      rhabdomyolysis and cerebral emboli is presented. The patient underwent successful
      mitral and aortic valve replacements and is only the third reported case with a
      successful outcome following surgery. Outbreak control measures were complicated
      by an equivocal result from guinea pig toxin tests.

PMID- 8522838
TI  - Recurrent meningococcal septicaemia and properdin deficiency.
AB  - A 32-year-old male presented with two episodes of meningococcal septicaemia, each
      of which was caused by a different serogroup of Neisseria meningitidis.
      Examination of the alternative pathway of complement revealed the rare X-linked
      disorder properdin deficiency (PD). Meningococcal Infection in complement
      deficiency states is discussed and the unusual features of this case are
      highlighted.

PMID- 8522839
TI  - Acute myelogenous leukaemia followed by non-Hodgkin's lymphoma in a patient with
      AIDs.

PMID- 8522840
TI  - Candida glabrata epididymo-orchitis: an unusual infection rapidly cured with
      surgical and antifungal treatment.
AB  - We report a case of epididymo-orchitis and secondary fungaemia caused by Candida
      (previously Torulopsis) glabrata in an 83-year-old male patient who had diabetes
      mellitus, urinary outflow obstruction and previous bladder malignancy. We believe
      this to be a previously unreported site of infection with C. glabrata and we
      describe its rapid and successful treatment with combination anti-fungal therapy.

PMID- 8522841
TI  - Plasma nitrate concentration and urinary nitrate excretion in patients with
      gastroenteritis.
AB  - The concentration of nitrate (the stable oxidation product of nitric oxide) in
      plasma and its excretion in urine was measured in 20 patients with a diagnosis of
      gastroenteritis. On day 1 of the illness plasma nitrate concentration was
      significantly elevated compared with a healthy control population (92.7 +/- 17.0
      mumol/l vs. 33.1 +/- 1.6 mumol/l; P < 0.001) and continued to be elevated on days
      2 and 3. Urinary nitrate excretion was also elevated. The plasma nitrate
      concentration correlated with disease severity as assessed by stool frequency and
      plasma urea concentration. Plasma nitrate concentration may be a sensitive and
      clinically useful indicator of severity of gastroenteritis.

PMID- 8522842
TI  - Prevalence of genital infections in medical inpatients in Blantyre, Malawi.
AB  - The limited information on the prevalence of sexually transmitted diseases (STDs)
      in Malawi suggests that they are common. In studies in Lilongwe in 1989 and
      Blantyre in 1990, the prevalence of STDs was 4.4% in unselected outpatients and
      42% in antenatal clinic patients respectively. Malawi is one of the countries
      worst affected by the HIV pandemic, with an estimated national HIV seroprevalence
      of 10% in the age group over 15 years and of 32% in pregnant women who attended
      antenatal clinics in Blantyre in 1993. Heterosexual intercourse is the main mode
      of HIV transmission in sub-Saharan Africa, accounting for up to 80% of cases of
      HIV infection. Concomitant genital ulcer disease facilitates sexual transmission
      of HIV. Non-ulcerative STDs may also play a role in facilitating sexual
      transmission of HIV but the evidence is less clear. The identification and
      treatment of people with STDs therefore presents an opportunity for decreasing
      HIV transmission. Queen Elizabeth Central Hospital (QECH) is the District
      Hospital for Blantyre, Malawi's largest city (about 500,000 population) and the
      tertiary referral hospital for Malawi's Southern Region. There are two general
      medical wards, one male and one female, to which about 11,000 patients were
      admitted in 1993. Bed occupancy can run at up to 150-200% and resources are
      limited. The top ten causes of admission are malaria, gastroenteritis, anaemia,
      pneumonia, dysentery, tuberculosis, AIDS, meningitis, hypertension and ascites.
      The leading causes of death are AIDS and tuberculosis.

PMID- 8522843
TI  - Mycobacterium kansasii scalp abscesses in an AIDS patient.

PMID- 8522844
TI  - Effect of biofilm culture on antibiotic susceptibility of lactobacilli causing
      endocarditis.

PMID- 8522845
TI  - Isolation of Salmonella typhi in a cutaneous ulcer.

PMID- 8522846
TI  - New nucleoside analogues--time for caution?

PMID- 8522847
TI  - Adenosine deaminase in cerebrospinal fluid during brucella meningitis.

PMID- 8522848
TI  - Severe forms of tick-borne meningoencephalitis in Slovenia.

PMID- 8522849
TI  - Adenovirus infections in compromised and other patients at a tertiary referral
      centre in Saudi Arabia.

PMID- 8522850
TI  - Efficacy and safety of alpha-interferon treatment for chronic hepatitis C in HIV
      infected patients. HIV-Hepatitis Spanish Study Group.
AB  - The efficacy and safety of recombinant alpha-interferon (IFN) therapy for chronic
      hepatitis C (CHC) was assessed in 57 HIV-infected individuals with CD4+ T cells
      above 200/mm3 and compared to the response obtained in 21 HIV-negative patients
      with CHC. IFN 5 megaU was given three times a week subcutaneously for 3 months.
      In responding patients, IFN 3 megaU three times a week was additionally
      administered for 9 months. After 8 months follow-up in HIV-infected patients, 38%
      (22/57) achieved normal (complete response, CR) alanine aminotransferase (ALT)
      values. Partial response (PR) was seen in 21% (12/57), and 40% (23/57) did not
      respond. Patients with CD4+ cells above 500/mm3 achieved CR in 58% (14/24) of
      cases compared to 24% (8/33) among those having a lower CD4+ count (P < 0.01).
      Females attained CR in 60% (9/15) of cases, and men in only 30.9% (13/42) (P <
      0.01). No serious side effects or opportunistic infections were observed during
      the study period. However, three (5.2%) patients showed a dramatic fall in total
      CD4+ T cell count after beginning IFN therapy. Among 21 HIV-negative patients,
      after 8 months follow-up, CR was achieved in 10 (47%), PR in four (19%), and
      seven (33%) did not respond. We concluded that IFN therapy seems to be well
      tolerated and useful in HIV-infected patients suffering CHC. The rate of CR was
      not significantly different compared to that observed in HIV-negative patients
      (38% vs. 47%), relative risk (RR) = 0.67 (0.19-2.37).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8522851
TI  - [Cancer on an ectopic kidney. Apropos of a case].
AB  - The authors report a case of renal cancer in ectopic situation. The diagnosis
      relies on intravenous pyelography and ultrasonogram. Angiography determines the
      vascularisation of the kidney and helps define the best surgical approach.

PMID- 8522852
TI  - [Priapism after intracavernous injection of PgE1 in two cases of impotence
      following total cysto-prostatectomy].
AB  - The authors report two cases of priapism of more than six hours, following
      intracavernous injection of 15 and 10 mcg PgE1 respectively, in six patients with
      impotence after radical cystoprostatectomy. Bearing in mind the proven safety of
      intracavernous injection of PgE1 in the treatment and diagnosis of erectile
      dysfunction, such a proportion of priapism in this group of patients has called
      our attention. It is probably due to an increased in the PgE1 intracavernous
      metabolism, due to the ligation of the penile venous drainage during surgery.

PMID- 8522853
TI  - [Priapism. Apropos of a case in a 10-year old child].
AB  - We report a case of post-trauma priapism observed in a 10-year old boy. Arterial
      blood flow was high with normal venous backflow, an exceptional situation in the
      child. Locoregional caudal anaesthesia was successful.

PMID- 8522854
TI  - [Indications of antiandrogens in benign hyperplasia of the prostate].

PMID- 8522855
TI  - [Place of endovesical "BCG Therapy" in superficial tumors of the bladder].
AB  - To better determine the role of endovesical BCG treatment for superficial tumours
      of the bladder, it is necessary to understand the natural history of these
      tumours and the prognostic factors; The goal is to better manage BCG as a
      preventive measure for relapse of superficial tumours of the bladder and to
      prevent possible progression by infiltration. It is also important to emphasize
      the possible complications of this therapy and the currently recommended
      precautions in order to carefully use this very effective method with the least
      possible morbidity.

PMID- 8522856
TI  - [Rectal injuries in radical prostatectomies for cancer. Survey of the ANFUC
      (Association National de Formation Urologique Continue) 1994].
AB  - This survey was conducted by 28 urologists members of the ANFUC who reported
      rectal wounds observed during radical prostatectomy procedures performed for
      cancer. There were 1,816 procedures reported, 1,785 suprapubic prostatectomies
      and 28 perineal operations. Kraske access was used in 3 cases. There were 33
      wounds to the rectum reported by 17 operators including 31 in suprapubic
      prostatectomies (1.7% of the operations) and 2 after transperineal operations
      (7.14%). Preoperative radiotherapy was never used and mechanical preparation was
      performed in most of the cases with rectal complications (27/33). The wound was
      sutured in all cases and a colonic derivation was required in 4. Retrospectively
      this procedure was judged unnecessary in 2 or 3 cases. The post-operative period
      was uneventful in all cases and the derivations were closed 2 or 3 months later.
      The conclusions drawn from this survey were the following: the rate of rectal
      complications in radical prostatectomy is higher in the perineal route. When no
      preoperative radiotherapy has been performed, simple suture of the rectal wound
      is sufficient and colonic derivation is not always necessary. It does not appear
      necessary to interpose an epiploic flap in such cases which would have the
      disadvantage of requiring opening the peritoneal cavity. These considerations are
      only applicable to the nonirradiated rectum. Preoperative radiotherapy would
      undoubtedly have a major effect, but we have had no experience in this series.

PMID- 8522857
TI  - [Iatrogenic injuries to the distal ureter during gynecologic interventions].
AB  - Surgical injury to the ureter is an important problem that confronts the
      urologist, the gynecologist and the general surgeon. The authors report 20 cases
      of iatrogenic pelvic ureteral injuries (22 ureters) observed after gynecological
      surgery between January 1985 and January 1995. The ureter was injured during
      ligation of the lumbo-ovarian vascular pedicle because it was inadequately
      protected during the operation. Open surgery and double pigtail stent insertion
      using retrograde route were used for treatment. The iatrogenic ureteral injury
      was in 18 patients unilateral and in the remaining 2 patients both ureters were
      damaged. As regards treatment, the authors recommend immediate repair, whenever
      the lesion is noticed at operation. In the post-operative period, ureteral stent
      or double pigtail stent insertion using balloon dilatation or ureteroscope, may
      be a successful conservative treatment. If the damage is only diagnosed
      subsequently, they recommend a ureterovesical implantation, using the psoas hitch
      bladder procedure or the Boari-Cassati-Kuss procedure if the lesion is in the
      lower ureter or a transuretero-ureterostomy if it is in the upper ureter.

PMID- 8522858
TI  - [Predictive value of urinary cytology in the diagnosis of urothelial tumors].
AB  - Between November 1991 and June 1993, 315 patients with urethral lesions were
      divided into two groups: group 1 included 215 patients with urethral tumours and
      group 2 included 100 patients with non-tumoural lesions. In all patients,
      urethral smears (performed on 3 consecutive days), pyelography and
      uretrocystoscopy (with bladder biopsy of observable lesions) were performed in
      all. The sensitivity of urine cytology examinations in the diagnosis of bladder
      cancer was found to by 80% with a specificity of 90%. The positive predictive
      value was 94.5% and the negative predictive value 67.7%. Urine cytology agreed
      with the diagnosis of urethral tumours especially well in advanced stage
      ulcerated tumours. These results underline the importance of cytology
      examinations in the exploration and follow-up of patients with urethral tumours.

PMID- 8522859
TI  - [Endoscopic resection of a peri-stenotic fibrous callus of the urethra using
      Guillemin's method].
AB  - The results observed in a series of 40 patients treated for urethral stricture by
      endoscopic resection of the callus after internal endoscopic urethrotomy
      (Guillemin's technique) are presented. The mean age of the patients was 57 years,
      with a follow-up of five years. The authors obtained 80% (32 patients) of very
      good results for urethral strictures less than 1 cm long. The success rate of the
      technique was 10% (4 patients) when the callus was between 1 and 2 cm long. The
      recurrence rate was high for strictures longer than 2 cm (4 patients) (10%).
      Complications consisted of 2 cases of acute epididymitis, 2 cases of urethral
      perforation, 2 cases of urethral haemorrhage, 2 cases of perineal haematoma and 3
      cases of meatal stenosis. The indications of this original technique therefore
      depend more on the length of the urethral stricture than on its topography or its
      aetiology.

PMID- 8522860
TI  - [Closure of a hypogastric urinary fistula after replacement enterocystoplasty
      with a flap of the rectus abdominis muscle].
AB  - Urinary fistulization to the skin is a rare complication of cystoprostatectomy
      with replacement enterocystoplasty. In two cases, fistulization did not respond
      to continuous drainage of the urine and was treated with a muscle flap using the
      abdominus rectus. This method offers rapid parietal repair giving a reliable
      rapid cicatrization since the interpositioned flap is well vascularized in an
      area of poor tissue quality.

PMID- 8522861
TI  - [Morphometry of the prostate in Black Africans. Apropos of 300 cases].
AB  - Sus-pubic route real time echographic, has allowed to determinate prostatic
      dimensions (antero-posterior, diameter, APD; mean transversal diameter: MID,
      cranio candal length CCL) volume and weight in the Black African on 300 subjects.
      The mean values of these parameter do not differ from European an American
      values. They increase progressively with age. They are higher in subjects
      presenting with history of affection of the urinary tract (especially gonococcus
      urethritis).

PMID- 8522862
TI  - [Hydrospermatocyst with ectopic junction of the ureter and ipsilateral renal
      agenesis. Diagnostic difficulties and contribution of magnetic resonance
      imaging].
AB  - A cystic dilatation of the right seminal vesicle due to an ectopic implantation
      of the right ureter was observed in a patient with ipsilateral renal agenesia.
      The embryology, symptomatology and radiological diagnosis, including magnetic
      resonance imaging, and treatment of this malformation are reported.

PMID- 8522863
TI  - [Acute thrombosed aortic dissection--its clinical manifestation and treatment for
      Stanford A type].
AB  - Ten patients (mean age of 63 years old) with acute thrombosed aortic dissection
      (ATAD) have been evaluated among 31 aortic dissections during past 10 years (from
      1985 to 1995). The six cases are Stanford A type and others are Stanford B type.
      The mean maximal diameter of aorta was 52 +/- 6 mm in Stanford A type and 41 +/-
      4 mm in Stanford B type. The ratio of true lumen was 78 +/- 14% to that of whole
      horizontal section area in thrombosed type and 34 +/- 19% in opacified type
      dissection. We had chosen conservative treatment for all ATAD. However, five
      patients with Stanford A type dissection needed to be operated on in short term
      periods. Three patients were operated upon within three days from onset, and
      another two patients were operated on 34th and 37th day from onset, respectively.
      ATAD is firstly treated medically and its prognosis is generally well. However,
      we proposed here that the conservative treatment for ATAD, especially Stanford A
      type dissection, must be reconsidered because of our many operations for ATAD in
      the follow-up periods.

PMID- 8522864
TI  - [Sequential coronary artery bypass grafting utilizing the internal thoracic and
      gastroepiploic artery as in situ grafts].
AB  - 36 consecutive patients (male:female = 33:3, mean age 57.3) underwent sequential
      coronary artery bypass grafting (CABG) utilizing the left internal thoracic
      artery (LITA, n = 30), right gastroepiploic artery (RGEA, n = 8) as in situ
      grafts. Two patients received sequential bypass grafting with both grafts
      simultaneously. No right internal thoracic arteries were used except for one as a
      free nonsequential graft. Taking into account the adjunctive venous anastomoses
      and the arterial nonsequential anastomoses, there were 3.5 anastomoses per
      patients. Proxymal side-to-side anastomosis of LITAs were all constructed on the
      diagonal branches except for one on the proxymal Left Anterior Descending
      Coronary Artery (LAD), whereas that of the RGEAs were on the proxymal Right
      Coronary Artery (RCA) (2), distal RCA (6) or distal circumflex (1). Distal end-to
      side anastomoses of LITAs were all on the LAD, and those of the RGEAs were on the
      distal RCA (3) or distal circumflex artery (5). Proxymal side-to-side anastomoses
      were always performed first, allowing us to assess the distal flow through the
      graft before we anastomose it to the distal branch. We routinely obtain a
      preoperative angiogram of the arterial grafts, which enable us to fully assess
      the suitability of the arteries as in situ grafts. There were no perioperative
      deaths, nor perioperative myocardial infarctions, however, two patients died of
      extracardiac causes at 42 and 68 days after operation respectively. For the
      thirty four survivors, followup was complete (4-49 months, average 12.3 months).
      One still had angina of Canadian Cardiovascular Society Classification (CCSC)
      class 2, and 33 were free of angina.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522865
TI  - [Evaluation of neck lymph node dissection and extended lymphadenectomy through a
      collar incision and median sternotomy for lung cancer].
AB  - Since 1983, 421 patients have been treated for lung cancer at this institute.
      Since 1988, neck lymph node dissection (11 cases) and new extended
      lymphadenectomy through a collar incision and median sternotomy (22 cases) have
      been conducted. Indications for this new radical operation are scalene,
      supraclavicular or highest mediastinal node involvement, or superior pulmonary
      sulcus carcinoma, in patients aged 70 or less without distant metastasis and
      NSCLC. No major complications and operative mortality were encountered in this
      study. Patients with scalene or supraclavicular node involvement showed poor
      prognosis. Postsurgical local recurrence was frequent. Whether resection in N3
      disease should be conducted or not, remains a point of controversy. The authors
      consider that lymphadenectomy should be conducted more extensively. A significant
      better survival of N2 disease and satisfactory prognosis of patients without
      metastasis of cervical lymph nodes demonstrates the effectiveness of neck lymph
      node dissection in the present superradical operation for lung cancer.

PMID- 8522866
TI  - [Respiratory failure after surgery for esophageal cancer and hypercoagulability].
AB  - Operation of esophageal cancer accompanies a big surgical stress and
      postoperative pulmonary complications such as respiratory failure are observed at
      high frequencies. On the other hand, when a big stress is added to a body, a
      state of hypercoagulation in which blood coagulation mechanism is abnormally
      enhanced appears and this state is closely related to organ failures but has many
      unknown points. So, we examined 39 patients given excision of esophageal cancer
      with respect to occurrence of postoperative respiratory failures, participation
      of coagulopathy in aggravation and their degrees before and after the operation
      to find out the relationship between postoperative respiratory failure and the
      state of hypercoagulation. We gave a diagnosis of respiratory failure to the
      patients whose respiratory index exceeded 1.5 on the day after operation but did
      not show atelectasis or hydrothorax. As a result, respiratory failures were
      observed in 7 out of 39 cases (17.9%). When a risk score (RS) of postoperative
      respiratory failure was determined using multivalent analysis (quantification
      type II) with preoperative factors such as age and function of heart, lung,
      liver, and kidney as well as preoperative blood coagulation factors, RS = 2.87
      (antithrombin-III (AT-III) less than 75%) +1.89 (age over 70 years) +1.78
      (respiratory index over 0.15) +1.44 (serum albumin less than 3.0 mg/dl) +1.28
      (cardiac index less than 3.0 l/min/m2) was obtained and a drop in preoperative AT
      III was considered a risk for occurrence of post operative respiratory failure.
      In contrast, referring changes in postoperative value of blood coagulation
      factors, a distinct rise in fibrinogen (FBG) appeared in early stage after
      operation in the respiratory failure group compared to the control group (p <
      0.01). Moreover, recovery in AT-III of blood coagulation factors and in
      plasminogen and antiplasmin of fibrinolytic factors was delayed (p < 0.05)
      indicating promotion of postoperative hypercoagulation state and delay in
      recovery of coagulation-fibrinolysis factors. However, participation of platelet
      factors was absent.

PMID- 8522867
TI  - [Effect of reimplantation response on recipient pulmonary hemodynamics in single
      lung transplantation].
AB  - Until now, reimplantation response (RR) has been thought to be a transient
      dysfunction of the transplanted lung in single lung transplantation. How does RR
      influence on the native lung in single lung transplantation? We studied the
      influence of RR to the native lung with 20 dogs which were divided separated into
      3 groups. In group I (6 dogs) and II (6), left lung allotransplantation without
      immunosuppression was performed. In group II, PGI2 was administered to the donors
      at 1 microgram/kg/min for 60 minutes iv drip infusion during lung extraction and
      super oxide dismutase (SOD) was administered to the recipients at 20 mg/kg just
      before reperfusion of the transplanted lung. In group III (8),
      allotransplantation with immunosuppression (CYA 20 mg/kg, AZ 4 mg/kg) was done
      using PGI2 and SOD in the same way as group II. In all groups doppler flow probes
      were attached to the ascending aorta and left pulmonary artery. For over 1 week,
      pulmonary hemodynamics was evaluated. In group I pulmonary arterial pressure
      increased up to 38.7 +/- 19.7 mmHg on 3 postoperative day, which showed
      significant difference (p < 0.05) from group II. An increase in vascular
      resistance of the transplanted lung was recognized right after transplantation in
      the both groups (0.212 +/- 0.058 mmHg/ml/kg to 0.487 +/- 0.114 in group I, 0.207
      +/- 0.072 to 0.407 +/- 0.172 in group II). However, vascular resistance of the
      right lung increased in group I against group II right after transplantation
      (0.182 +/- 0.116 to 0.367 +/- 0.195 in group I, 0.183 +/- 0.116 to 0.214 +/-
      0.149 in group II), which showed significant difference (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8522868
TI  - [Roll repair of nonconfluent pulmonary artery].
AB  - We reviewed the repair of nonconfluent pulmonary artery using a roll to clarify
      indication of this operation, operative technique (especially the material and
      the size of conduit) and possibility of total correction. Eleven patients (mean
      age: five years) and 13 operations including two reoperations were reviewed. The
      material of the roll was xenopericardium in nine and artificial graft in four
      operations. No operative death and late death occurred. Five patients required
      reoperations from three occlusion and two severe stenosis of the roll. Three of
      nine xenopericardial roll needed reoperations and in two reoperated cases, the
      roll had been placed behind the aorta. In contrast, one artificial graft needed
      reoperation. The diameter of the roll was compared with that of normal pulmonary
      artery estimated from the body surface area. If the roll was too large (more than
      125% normal) or too small (less than 100% normal), the luminal diameter of the
      roll became significantly smaller than appropriate-sized roll (p = 0.002). The
      size of nonconfluent side of the pulmonary artery also affect the result of
      repair. In occluded or stenotic cases, the unilateral PA index was significantly
      smaller than good patent cases (p = 0.014). Total correction was possible in
      eight cases (73%) including four Rastelli operation, two right ventricular
      outflow patch enlargement, and two modified Fontan operations without operative
      death. Thus preoperative evaluation of the pulmonary artery size and anatomy,
      selection of roll material and size matching seemed to be important for
      successful roll repair of nonconfluent pulmonary artery.

PMID- 8522869
TI  - [Successful surgical treatment for ruptured distal aortic arch aneurysm into
      lung].
AB  - We report successful aortic arch replacement using continuous retrograde cerebral
      perfusion (CRCP) for the three cases of ruptured distal aortic arch aneurysm
      (DAAA) into the left lung. All of them, who had preoperative episodes of
      hemosputum and hemoptysis, were diagnosed rupture of DAAA into the lung with
      computed tomography, magnetic resonance image, aortography or transesophageal
      echo. Following urgent graft replacement of the aortic arch or repair of the
      rupture on the suture line in the previous arch vessel reconstruction was carried
      out safely through median sternotomy approach. The left upper lobe of lung
      adherent tightly to the DAAA wall was not dissected to prevent the lung from
      bleeding, air leakage and infection. All of them, who awoke smoothly after CRCP,
      did not developed any pulmonary complications and survived uneventually. We
      concluded that median approach and not tearing lung from DAAA wall might be key
      points for successful operation in cases of ruptured DAAA into lung and that CRCP
      is an safe and useful method to protect brain in such cases.

PMID- 8522870
TI  - [Tricuspid valve replacement for infective endocarditis in drug addict--a case
      report].
AB  - For right-sided endocarditis associated with drug abuse a successful treatment by
      tricuspid valve replacement was reported. A 34-year-old female who had a history
      of intravenous drug use for 14 years was admitted with complaints of chest pain,
      fever and dyspnea. A large vegetation about 47 mm in size attached to the
      tricuspid valve with tricuspid regurgitation was detected by echocardiography.
      Methicillin-resistant staphylococcus aureus was isolated in a blood culture.
      Because infection was persistent and uncontrollable in spite of sensitive
      multiple antibiotic regimens, tricuspid valve replacement using a St. Jude
      Medical valve was successfully performed with excision of markedly destroyed
      leaflets and debridement of the infectious lesions. After surgery the patient has
      been free from infection for 3 years.

PMID- 8522871
TI  - [Successful valvuloplasty for isolated tricuspid regurgitation due to traumatic
      ruptured papillary muscle].
AB  - A 44-year-old man suffered from an traffic accident on May 27, 1994. He was
      transferred to a hospital because of emergent operation for a laceration of
      liver, right-sided hemothorax and pneumothorax. After surgical treatment for
      these lesions, he was doing well. However, systolic murmur appeared from August,
      1994. By echocardiography and cardiac catheterization, he was diagnosed of
      isolated tricuspid regurgitation due to traumatic ruptured papillary muscle.
      Because right heart failure was progressive, an operation was recommended. At
      operation, annular dilatation of tricuspid valve and ruptured papillary muscle of
      anterior leaflet were found. And the ruptured end of right ventricular aspect was
      recognized. Therefore, we performed tricuspid valvuloplasty and annuloplasty.
      Postoperative course was uneventful. And residual regurgitation was not detected
      by right ventriculography. Especially, in patients with tricuspid regurgitation
      due to ruptured papillary muscle, symptoms usually begin soon after trauma.
      Therefore, an operation should be recommended promptly in the presence of right
      heart failure not relieved by medical treatment. And an earlier operation could
      increase the feasibility of tricuspid valvuloplaty, and the possibility of
      maintaining sinus rhythm.

PMID- 8522872
TI  - [Successful graft replacement of a thoracic aortic aneurysm in a patient with
      Ehlers-Danlos syndrome].
AB  - We have experienced graft replacement of a thoracic aortic aneurysm in a 42-year
      old man with Ehlers-Danlos syndrome. The patient received graft replacement of
      the abdominal aortic aneurysm 1 year before this thoracic operation but had no
      abnormality in his outside appearance. Thoracic CT scan revealed a thoracic
      aortic aneurysm of 80 mm in maximal diameter. We performed a graft replacement of
      the thoracic aorta from the ascending aorta to the proximal descending thoracic
      aorta using deep hypothermia and retrograde cerebral perfusion. The aortic wall
      was so thin that we used Teflon felt for reinforcement of graft anastomosis at
      the outside wall of the aortic stump. Type III collagen stain of the resected
      aortic wall showed deficiency of type III collage, which was consistent with
      Ehlers-Danlos syndrome (type IV). Postoperative course was uneventful, and the
      patient returned to his ordinary life.

PMID- 8522873
TI  - [A case of non-small-cell primary lung cancer invading distal aortic arch and
      left subclavian artery].
AB  - A 71-year-old male patient was referred to our institute for abnormal mediastinal
      shadow. It was proved to be squamous cell carcinoma arising in left S1 + 2 and
      involving distal aortic arch and left subclavian artery (T4N2M0 Stage IIIB). The
      cancer responded well to the preoperative induction therapy and it was resected
      completely with associated resection of distal aortic arch and left subclavian
      artery. Both arteries were replaced with Dacron grafts. With induction therapy
      and extended operation, this patient of non small cell T4 primary lung cancer is
      expected to acquire long term survival.

PMID- 8522874
TI  - [Staged bilateral upper lobectomy of pathologically different synchronous double
      primary cancer].
AB  - A case of double primary lung cancer was reported, one of which was peripheral
      type of adenocarcinoma of the right lung and the other was central type of
      squamous cell carcinoma of the left. A 66-year-old male was referred to our
      hospital on Nov. 2 1991, because a coin lesion at the right S1 was pointed out on
      chest X-ray. On bronchoscopy, a nodular tumor at the orifice of the left B3 was
      unexpectedly found. Biopsy of the left B3 tumor and washing cytology of the right
      B1 led to a diagnosis of left moderately differentiated squamous cell carcinoma
      (clinical T1N0 M0) and right adenocarcinoma (clinical T1N0M0). A right upper
      lobectomy was first performed with R2 lymph node dissection on Nov. 25 1991. Post
      operatively, it was confirmed that the lesion was histologically poorly
      differentiated adenocarcinoma of the right S1, and the pathological stage was
      T2N0M0. Two weeks after the operation, chemotherapy of CDDP, VDS and MMC was
      given because of suspicion of rapid metastasis to the left hilar lymph nodes.
      Left upper lobectomy with R2 dissection was performed 7 weeks after the initial
      operation. Pathological findings showed squamous cell carcinoma originating from
      B3 with inflammatory lymphadenopathy and pathological evaluation was T1N0M0. He
      was discharged after an uneventful course of 3 weeks after the second operation.
      There are many reports that limited operations are recommended for each lesion in
      double primary lung cancer to reserve the pulmonary function. However, limited
      interventions cause frequently local metastasis, especially in peripheral type
      adenocarcinoma more than 3 cm in diameter and central type squamous cell
      carcinoma with lymph node metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522875
TI  - [A case of successful redo-operation for active prosthetic valve endocarditis
      after modified Bentall operation].
AB  - A redo-operation for active prosthetic valve endocarditis after modified Bentall
      operation is reported. A 42-year-old man associated with Marfan syndrome was
      transferred to our hospital with complaints of high fever and general fatigue. A
      modified Bentall operation for acute aortic dissection was done five years ago.
      The aortic arch and descending thoracic aorta were replaced with prosthetic graft
      because of aneurysmal dilatation four years ago. Transesophagial echogram
      revealed a developing vegetation below the prosthetic valve and at the left
      ventricular outflow. A redo-operation of translocation method with Pieler method
      for coronary reconstruction was performed using a prosthetic valve of SJM 21 mm
      in size. After operation, hemolysis suddenly appeared and hepatic dysfunction
      gradually progressed. Reoperation was necessary for the redo-operation and and a
      SJM 21 mm valve was replaced with a new 25 mm SJM valve interposed between the
      graft. Hemolysis was immediately improved. A redo operation of translocation
      method with Pieler method for coronary reconstruction showed a good results.

PMID- 8522876
TI  - [Mitral valve replacement with homemade heterologous pericardial roll valve for
      mitral regurgitation after repair of complete atrioventricular septal defect].
AB  - Repair of using the double patch method was performed on a 6-month old child with
      Down's syndrome. However, at 1 year and 4 months (BW: 3.6 kg), the patient's
      resulting mitral regurgitation became severe and clinically unmanageable,
      necessitating further operation. At operation the anterior leaflet of the mitral
      valve was lifted up at the anterolateral side due to the patch attached to the
      interventricular septum, which restricted the valve from closing completely.
      Moreover, secondary severe hardening of the valve tissue made it difficult to
      reconstruct the valve. Since the diameter of the valve was only 13 mm after
      resection, making the impossible use of a standard prosthetic valve, we
      constructed a new roll valve out of a heterologous pericardium. Almost no
      regurgitation was observed and prognosis was favorable although a pattern of
      mitral stenosis was observed. The patient died 6 months later due to the
      worsening of respiratory infection before a reoperation could be performed. Post
      mortem examination revealed comparatively good valve function except mitral
      stenosis due to inadequate valve size. This technique has practical application
      for mitral valve replacement of small valve annuli of infants when other methods
      are not feasible.

PMID- 8522877
TI  - [Thromboembolectomy using cardiopulmonary bypass for acute pulmonary embolism
      with nephrotic syndrome--report of a case].
AB  - We report a case treated with thromboembolectomy using cardiopulmonary bypass for
      acute pulmonary embolism caused by nephrotic syndrome. A 19-year-old male with
      poorly controlled nephrotic syndrome was admitted associating with severe shock.
      An acute pulmonary embolism was diagnosed by ECG and echocardiography. Despite
      the intensive thrombolytic therapy, hemodynamics was deteriorated. Pulmonary
      arteriography demonstrated obstruction of left main pulmonary artery and partial
      defects of right pulmonary artery bifurcation and right middle-lower pulmonary
      arteries. An emergent thromboembolectomy using cardiopulmonary bypass was
      performed successfully. In conclusion, an emergent surgical treatment is required
      in the case of acute massive pulmonary thromboembolism which shows hemodynamic
      deterioration in spite of recent intensive medical treatment.

PMID- 8522878
TI  - [A case of Addison's disease complicated by lung carcinoma treated with surgical
      resection--a case report].
AB  - Surgery was successful in a 72-year-old man with Addison's disease complicated by
      right lower lobe carcinoma of the lung. The patient had been diagnosed Addison's
      disease 25 years earlier and had been treated with cortisone acetate 25 mg every
      morning. A tumor shadow was found in the right lower lobe of the lung on chest X
      ray. Squamous cell carcinoma was diagnosed by cytological examination. Right
      lower lobectomy with partial resection of the right diaphragma and lymph-node
      dissection were performed. The bronchial stump was closed using Sweet's method
      and covered with a pericardial fat pad. The intra- and post-operative course was
      uneventful with intravenous administration of adequate doses of hydrocortisone.
      The patient has been free from the carcinoma for two years.

PMID- 8522879
TI  - Analytical solutions to a multicylinder somatic shunt cable model for passive
      neurones with spines.
AB  - A multicylinder somatic shunt model for spiny, passive neurones is considered.
      The spines are modelled as a continuum (after Baer & Rinzel, 1991), coupled
      through the spread of dendritic voltage. A general solution is developed and a
      relationship governing the contribution of dendrites, soma, and spines to the
      voltage response is derived.

PMID- 8522880
TI  - Some aspects of the coevolution of virulence and resistance in contact
      transmission disease processes with ecological constraints.
AB  - In this paper, the author constructs a general, continuous-time dynamical model
      of a coevolutionary host-microparasite interaction, which incorporates host
      resistance (degree of susceptibility to invasion by the parasite) and parasite
      virulence (pathogenicity and transmission efficiency). Discrete classes of
      resistance type and virulence type are allowed. It is assumed that high virulence
      parasite strains are able to take over hosts already occupied by lower virulence
      strains. Heritability of host resistance is assumed, but specific assumptions
      about the genetics of such inheritance are avoided. Instead, a 'neutral' view is
      adopted, which assumes that the disease process is the sole selective force
      acting on a disease-free resistance distribution. This allows the dimensionality
      of the model to be kept lower than corresponding explicitly population-genetic
      models. Ecological factors are taken into account via density dependence in host
      encounter rate (which also influences transmission properties of the disease via
      contact transmission), and by density dependence in host fecundity. Two distinct
      host types are considered, which we call 'bunchers' and 'separators',
      characterized by the form of reaction of the encounter rate to changes in host
      density. Detailed analyses are given for versions of the model having: (a) one
      resistance class and one virulence class; (b) two resistance classes and one
      virulence class; (c) two resistance classes and two virulence classes. Sufficient
      conditions are found in case (c) for the low resistance type to be eliminated by
      the coevolutionary process. Features which might tend to promote resistance
      polymorphism are also discussed.

PMID- 8522881
TI  - [Effect of sex steroids on serum amyloid P-component (female protein) in rats].
AB  - Serum amyloid P-component (SAP) has been designated as a female protein in
      hamsters. But such a distinction is not made for rats. In order to investigate
      the effects of sex-steroids on the SAP level in rats, SAP was purified from
      Wistar rats by affinity chromatography of phosphorylcholine, followed by gel
      filtration. Anti-SAP was raised through the immunization of rabbits with the rat
      SAP and Freund's adjuvant. Sample sera were obtained from 180 young and old rats,
      after which rats were injected with estradiol (E2), testosterone (T) or
      dehydroepiandrosterone (DHEA). Sera were serially obtained from the tail vessels
      until the 8th day after injection. The SAP level was assayed by micro single
      radial immunodiffusion. As the rats aged, the SAP levels increased from 2.9 mg/dl
      at 11 weeks to 10.7mg/dl at 58 weeks. In 37-week-old rats, the SAP levels in
      females (6.3 +/- 1.8 mg/dl) were significantly (p < 0.001) higher than those in
      males (3.9 +/- 1.0 mg/dl). The SAP levels did not change after T administration,
      but were increased rapidly by E2 administration, especially in young male rats
      (increased from 2.6 +/- 0.2 mg/dl to 4.9 +/- 0.7 mg/dl). The SAP levels were
      decreased significantly (p < 0.05) by DHEA injection. Serum E2 levels in young
      (11 wk) male rats were very low before E2 injection, and rose steeply on the 2nd
      day. From these findings, the different SAP levels in mature female and male rats
      are attributed to E2.

PMID- 8522882
TI  - [Retinopathy and perinatal outcome in diabetic pregnancy].
AB  - Sixty patients with diabetes mellitus (DM) antedated pregnancy were enrolled;
      seven had proliferative retinopathy, 13 had simple retinopathy, and 40 were
      intact. Diet and/or insulin was prescribed to adjust their glucose control at
      fasting to < 100 mg/dl, as well as at 2 hours postprandial to < 120 mg/dl.
      Glycohemoglobin (Hemoglobin A1c) levels ranged between 5.4% and 6.4% in the third
      trimester in three groups. Incidences of pregnancy complications (toxemia,
      hydramnios, urinary tract infection and cesarean section) and neonatal
      complications (low Apgar score, hypoglycemia, jaundice, polycythemia, respiratory
      distress syndrome and anomaly) did not differ significantly with the grade of
      retinopathy. Compared with the intact group, the duration of DM was significantly
      longer in the retinopathy groups and the incidence of fetal distress was
      significantly higher in the proliferative retinopathy group. In ten of 60
      patients (16.7%) the grade of retinopathy progressed during pregnancy. In four
      patients photocoagulation was performed for neovascularization, and proved to be
      effective. There was a tendency for those whose retinopathy progressed to the
      proliferative stage during pregnancy to have larger decreases in glycohemoglobin
      and for their retinopathy to worsen after delivery. With tight maternal glucose
      control and intensive fetal surveillance, we obtained good perinatal outcome in
      pregnancies with diabetic retinopathy, as compared to diabetic pregnancy without
      diabetic microangiopathy. Careful and frequent monitoring of retinal changes
      should be required during pregnancy and the postpartum period.

PMID- 8522883
TI  - [A study for predicting toxemia of pregnancy by the diastolic notch in pulsed
      Doppler flow velocity waveforms of the uterine arteries--quantitative analysis of
      the diastolic notch as uterine arterial index (UTAI)].
AB  - To investigate the ability of measurement of the diastolic notch in Doppler flow
      velocimetry to predict development of toxemia of pregnancy, analysis of
      uteroplacental and fetal blood flow waveforms was performed. The waveforms were
      analyzed by calculating the resistance index (RI) and the pulsatility index (PI)
      and were investigated whether diastolic notches existed or not. In the
      prospective study, the uterine arterial index (UTAI; an index introduced to
      evaluate the degree of diastolic notch quantitatively) was also calculated.
      RETROSPECTIVE STUDY: The waveforms in the uterine arteries, the umbilical artery
      and the fetal vessel (inferior vena cava, descending aorta and middle cerebral
      artery) were measured in 153 pregnant women. PROSPECTIVE STUDY: Uterine artery
      velocimetry was performed at 16-23 weeks' gestation in 387 pregnant women. RESULT
      1: Subjects with a diastolic notch had significantly higher rates of development
      of toxemia of pregnancy. Indexes of the fetal blood flow waveforms had no
      significant correlations with the development of toxemia of pregnancy. RESULT 2:
      UTAI showed an equivalently high negative predictive value (98.1%) and higher
      positive predictive value (17.6%) than RI (98.2%, 10.2% respectively) and PI
      (98.7%, 12.7% respectively). CONCLUSION: UTAI measurement was more useful for
      predicting toxemia of pregnancy than RI or PI.

PMID- 8522884
TI  - [Relationship between catecholamine levels in amniotic fluid and fetal blood flow
      in fetal distress].
AB  - Eighteen cases of complicated pregnancy with fetal distress and/or pregnancy
      toxemia who underwent Cesarean section (CS) before onset of labor were studied.
      The resistance indexes (RI) of the umbilical artery (UA) and fetal middle
      cerebral artery (MCA) were measured by Doppler echography prior to CS. UA blood
      and amniotic fluid (AF) were obtained during CS and the pH value for the UA and
      the concentrations of norepinephrine (NE) and epinephrine (E) in AF were
      measured. A significant correlation between the pH value, MCA-RI/UA-RI ratio and
      the levels of NE and E in amniotic fluid was obtained. NE and E concentrations in
      AF obtained from the patients with fetal distress before the onset of labor were
      1.92 +/- 0.54 and 1.48 +/- 0.28ng/ml and these concentrations were significantly
      higher then those from elective CS. The deviations (delta SD) of RI from the
      normal mean for corresponding gestational age in fetal distress were -4.21 +/-
      0.94 in MCA and 1.31 +/- 0.48 in UA. A negative correlation between the pH value
      and delta SD (UA) was observed but the pH value correlated positively with delta
      SD (MCA). Furthermore, the MCA-RI/UA-RI ratio showed a significant negative
      correlation with the NE and E levels in AF. These results suggest that fetal
      catecholamine affects fetal blood flow in fetal distress.

PMID- 8522885
TI  - [The effect of danazol and buserelin on natural killer activity in experimental
      endometriosis of the rat].

PMID- 8522886
TI  - [Evaluation of prophylactic approach to reduce incidence of ovarian
      hyperstimulation syndrome in in vitro fertilization].

PMID- 8522887
TI  - [A case of uterine endometrial cancer complicated post transfusion fatal
      fulminant hepatitis caused by hepatitis B virus with DNA mutation in precore
      region].

PMID- 8522888
TI  - [A case of beta 2-glycoprotein I-independent antiphospholipid syndrome].

PMID- 8522889
TI  - [Molecular structure and function of matrix proteins in developing enamel-
      amelogenin and enamelin].

PMID- 8522890
TI  - [Discussion on the location of the artificial crown margin].

PMID- 8522891
TI  - [Initial corrosion of dental casting alloys in the oral environment].
AB  - In order to study the initial corrosive changes of dental casting alloys in the
      mouth, the condition and composition of the proximal surface of the class II
      inlay were analyzed by the scanning electron microscope (SEM) and the electron
      probe microanalyser (EPMA). These analyses on the same small areas of the
      proximal surface were carried out every week for four weeks. The results were
      compared with the condition and composition of the preplacement in the mouth, and
      also with the data from former studies. 1. Changes observed in the 70Au-3Pt-3Pd
      10Ag-14Cu alloy (Au-alloy) were slight in comparison to the other alloys in this
      experiment, both on the surface condition and composition. 2. The 12Au-45Ag-20Pd
      18Cu alloy (Pd-alloy) appeared to be stable in the mouth, but the changes were
      greater than that of the Au-alloy. 3. The Au- and the Pd-alloys appeared to be
      stabler after hardening heat treatment. 4. The greatest change was observed in
      the 65Ag-22Sn-13Zn alloy. 5. Little change was found in the 72Ni-19Cr-6Si alloy
      by visual inspection, but the dendritic structure was observed by SEM. 6. Almost
      all these changes of the alloys in this study showed somewhat greater changes
      than those observed in the conventional basic immersion tests of alloys.

PMID- 8522892
TI  - [Study on cadmium-induced metallothionein-like protein in bone marrow of rabbit].
AB  - It has been recognized that metallothionein (MT) is a low molecular-weight
      protein and can be induced by heavy metals in several organs. Most studies on MT
      focus on the liver and kidney, and little is known about MT in the bone marrow.
      In the present study, the characterization of the MT-like protein in bone marrow
      of rabbits was investigated after the injection of CdCl2. A dose of 8 x 10(-5)
      mol/kg CdCl2 was injected subcutaneously into Japanese White Rabbits (male, 3.5
      kg) for five days. Twenty-four hours after the last CdCl2 injection, the bone
      marrow, liver and kidney were removed immediately and frozen. The fractions of
      metal-binding protein were obtained by gel filtration (Sephadex G-75) of cytosol
      from the tissues of Cd-treated rabbit. They were heat-stable and low molecular
      weight (under 10 kDa) proteins. They had high absorption at 250 nm. These
      observations suggest that the injection of CdCl2 induced MT-like protein in bone
      marrow.

PMID- 8522893
TI  - [Effect of an additional cathode on the electrolytic-polishing of titanium
      specimens with non-aqueous electrolyte].
AB  - The purpose of this study was to polish electrolytically a large maxillary
      denture base-shaped titanium specimen with non-aqueous electrolyte. The test
      specimen was prepared by bending a sheet of titanium plate. An additional cathode
      was made by cutting off part of a cylindrical cathode. The effects of the shape
      and position of the additional cathode were investigated. Selected factors of the
      additional cathode were as follows: the connecting point between the additional
      cathode and the cylindrical cathode, the end position of the additional cathode,
      and the distance between the additional cathode and the titanium specimen. An
      acceptable polished titanium surface was obtained when the connecting point was
      below the electrolyte surface, the end position of the additional cathode was at
      a similar level to the bottom of the specimen, and the distance between the
      additional cathode and the specimen was 10 mm.

PMID- 8522894
TI  - [Influences of tooth contact patterns during mandibular retrusion on the terminal
      jaw relation of habitual closures].
AB  - Influence of tooth contact patterns during mandibular retrusion on the terminal
      jaw relation (TJR) of habitual closures were investigated on five subjects. A
      maxillary stabilization splint with steep retrusive contacts was fabricated and
      applied to each subject for one week in the first series of this experiment. In
      the second series, steepness of the retrusive contacts was reduced and the splint
      with flat occlusal surface was applied. After each series, subjects were asked to
      perform habitual closures with an intraoral central bearing device and their TJR
      was recorded. The results as follows: 1. TJR was influenced by the tooth contact
      pattern during mandibular retrusion. 2. TJR recorded after the second series
      tended to be more posterior than that after the first series. 3. It was suggested
      that the position of the condyle might change posteriorly with flatter retrusive
      contacts. 4. These results suggest the necessity of appropriate tooth guidance
      during mandibular retrusive movements for the dentulous subjects.

PMID- 8522895
TI  - [A case of injured unerupted permanent tooth in a child].
AB  - Children with trauma visit frequently the department of oral and maxillofacial
      surgery. The treatment for injured permanent teeth is different from that for
      injured deciduous teeth. We have experienced a case of a 9-year-old boy with an
      injured unerupted immature permanent tooth with tooth crown fracture. When the
      tooth erupted gradually, fractured pieces were removed three times, and indirect
      pulp capping was performed. Three years after the injury eruption was almost
      completed and pulp was alive, even though the dental roentgenograph showed
      obliteration of the crown pulp cavity.

PMID- 8522896
TI  - [Jaw position, head position, body posture: development of an integrated system
      of examination, Part I].
AB  - Recently in the field of clinical orthodontics, there has been increased interest
      in the relationship between jaw and head position, sleep apnea, and equivocal
      symptoms occurring in head, neck and shoulder. It has already been determined
      that a relation exists between head posture and mode of breathing. Since the
      craniofacial skeleton is supported by the cervical, thoracic and lumbar
      vertebrae, the head position might have some biomechanical connection to total
      body posture. Therefore, an integrated system of examining jaw position, head
      position and body posture is being developed.

PMID- 8522897
TI  - The 20-year anniversary of the Louisiana Medical Malpractice Act of 1975, 'Act
      817 of 1975'. 'A rescue from danger'. A tribute to John C. Cooksey, MD.

PMID- 8522898
TI  - ECG of the month. Twin-farction. Acute myocardial infarction.

PMID- 8522899
TI  - Hypopharyngeal carcinoma.
AB  - Hypopharyngeal carcinomas are considered indolent, silent tumors. These tumors
      dictate a high index of suspension. They can present with a myriad of symptoms
      and clinical complaints. The silent nature of these tumors unfortunately causes a
      high number of patients to present with advanced disease. A multimodality
      approach is often used. Although our approach to this disease has advanced, the
      overall mortality remains high at 5 years.

PMID- 8522900
TI  - A 38-year-old man with nephrotic syndrome, episodic fever and abdominal pain.
AB  - The differential diagnosis for a 38-year-old white man with a chronic fever
      associated with nephrotic syndrome is discussed in the setting of a
      clinicopathological conference at Louisiana State University Medical Center in
      Shreveport, Louisiana. The etiology and pathophysiology of fever-associated
      nephrotic syndrome are discussed.

PMID- 8522901
TI  - Advice for the '90s traveler.

PMID- 8522902
TI  - November 1845 and 1895.

PMID- 8522903
TI  - An 81-year-old woman with an abdominal mass.
AB  - An 81-year-old woman was admitted with a large abdominal mass that had grown
      rapidly over the previous few months. The differential diagnosis, pathology, and
      treatment of such masses are discussed.

PMID- 8522904
TI  - Blunt needle infusion of local anesthetics or narcotic analgesics into operative
      wounds or joints.
AB  - Local anesthetics or narcotic analgesics introduced into surgical wounds have
      been noted to provide pain relief. These agents are typically infused into the
      postoperative joint or wound using a standard beveled needle or by pressing the
      syringe hub against the incision without a needle. We present an alternative
      method of administering these agents to provide pain relief in the orthopedic
      patient. A blunt needle is used to infiltrate the postoperative joint or wound
      with local anesthetics or narcotic analgesics.

PMID- 8522905
TI  - Self-organization of an oscillatory neural system.
AB  - Hebbian dynamics is used to derive the differential equations for the synaptic
      strengths in the neural circuitry of the locomotive oscillator. Initially, neural
      connection are random. Under a specified arborization hypothesis relating to the
      density of neural connections, the differential equations are shown to model the
      self-organization and the stability of the oscillator.

PMID- 8522906
TI  - Development of distributed image database combined with clinical information in
      hospital information system.
AB  - We have developed a distributed image database system composed of the data in our
      medium-scale PACS that provides diagnostic-quality images and the data in our
      HIS. INFORMIX software was used to construct the distributed relational database.
      The data in HIS were retrieved using several programs written in COBOL. Image
      data in PACS were retrieved using ACR-NEMA protocols. The data retrieved from the
      HIS database involved medication, disease entities, laboratory test results, etc.
      Therefore, the image data on a given patient can be retrieved by specifying the
      name of the disease in our database system. Our method offers a practical one to
      make a global database system to maintain the integrity of the data in the HIS
      and the PACS. The combination of image data and disease made it quite easy to
      make a sample database for developing a computer-aided diagnostic system.

PMID- 8522907
TI  - A study on 3D Monte Carlo modeling of photon propagation through tissue.
AB  - Monte Carlo techniques have become popular in modeling of the random events with
      advantage of powerful computing systems. Especially they have been applied to
      simulate processes involving random behavior such as diffusion of the Gamma rays
      through matter and electron concentrations in semiconductors. Recent medical
      innovations such as Computer Automated Tomography (CAT) and Positron Emission
      Tomography (PET) are ideal for Monte Carlo modeling techniques. This paper
      presents derivation and results of the three dimensional Monte Carlo simulation.
      The results are presented for tissue interactions with photons at wavelength of
      207 nm X rays and 630 nm red light. Resulting values of model tissue have been
      interpolated and mapped into two-dimensional pattern in gray tone. Combination of
      two-dimensional patterns allow a reconstruction in three dimensions.

PMID- 8522908
TI  - Graphical user interface for the analysis of noise induced hearing loss.
AB  - We have developed a Windows-based computer program which will help the user to
      collect data needed for calculation models of noise induced hearing loss (NIHL).
      The program has a graphical user interface and it includes several methods to
      calculate NIHL. We have tried to make our system to cover all the factors
      concerning NIHL and also to take into account other possible reasons of hearing
      loss. The system is used not only for estimating noise induced hearing loss, but
      also as a systematic way to collect data for future evolution of new models and
      for other research purposes. For this sake the program asks some questions that
      are not currently included to these models, but which have been shown to have
      some impact on noise induced hearing loss.

PMID- 8522909
TI  - Allocation of surgical procedures to operating rooms.
AB  - Reduction of health care costs is of paramount importance in our time. This paper
      is a part of the research which proposes an expert hospital decision support
      system for resource scheduling. The proposed system combines mathematical
      programming, knowledge base, and database technologies, and what is more, its
      friendly interface is suitable for any novice user. Operating rooms in hospitals
      represent big investments and must be utilized efficiently. In this paper, first
      a mathematical model similar to job shop scheduling models is developed. The
      model loads surgical cases to operating rooms by maximizing room utilization and
      minimizing overtime in a multiple operating room setting. Then a prototype expert
      system which replaces the expertise of the operations research analyst for the
      model, drives the modelbase, database, and manages the user dialog is developed.
      Finally, an overview of the sequencing procedures for operations within an
      operating room is also presented.

PMID- 8522910
TI  - The relationship between hospital per diem billing and DRG reimbursement for
      urban trauma patients.
AB  - STUDY OBJECTIVE: To study the relationship between a trauma center per diem
      charges and medicare DRG reimbursement. DESIGN: Retrospective comparison of
      charges ($630/day, $1500/ICU day) and hypothetical DRG reimbursement using
      medical records ICD-9 N and P codes and version 5.0 of grouper. SETTING: An urban
      level I trauma center that participates in a trauma system that serves a
      population of three million people. PATIENT POPULATION: Trauma patients > or = 16
      years old (mean age of 32 years) admitted and discharged between 1/1/88 and
      9/30/88. The group was 86% male, 75% black, with a blunt mechanism of injury in
      64%. The mean ICU stay was 0.9 days, and the mean total length of stay was 5.0
      days. RESULTS: Total per diem charges were $8,652,159, and DRG reimbursement was
      $8,636,505, causing a net loss of $15,654, or 0.2% of charges. Mean charges and
      reimbursement did not differ for the entire group. The mean loss per patient was
      $8. Mean charges and reimbursement differed in penetrating trauma patients (mean
      loss = $138), as well as those with different lengths of stay. The correlation
      between charges and reimbursement was 0.42; for penetrating trauma patients, the
      correlation was 0.58. (p < .001) CONCLUSION: If DRG reimbursement were provided
      for all admitted trauma patients, the amount would equal per diem rates. Trauma
      centers with similar patients and lengths of stay can use these per diem rates to
      estimate DRG reimbursement.

PMID- 8522911
TI  - Forecasting without historical data: Bayesian probability models utilizing expert
      opinions.

PMID- 8522912
TI  - Crime laboratory proficiency testing results, 1978-1991, II: Resolving questions
      of common origin.
AB  - A preceding article has examined the origins of crime laboratory proficiency
      testing and the performance of laboratories in the identification and
      classification of common types of physical evidence. Part II reviews laboratory
      proficiency in determining if two or more evidence samples shared a common
      source. Parts I and II together review the results of 175 separate tests issued
      to crime laboratories over the period 1978 to 1991. Laboratories perform best in
      determining the origin of finger and palm prints, metals, firearms (bullets and
      catridge cases), and footwear. Laboratories have moderate success in determining
      the source of bloodstains, questioned documents, toolmarks, and hair. A final
      category is of greater concern and includes those evidence categories where 10%
      or more of results disagree with manufacturers regarding the source of samples.
      This latter group includes paint, glass, fibers, and body fluid mixtures. The
      article concludes with a comparison of current findings with earlier LEAA study
      results, and a discussion of judicial and policy implications.

PMID- 8522913
TI  - The evaluation and implementation of match criteria for forensic analysis of DNA.
AB  - This study describes a method for establishing match criteria used in forensic
      DNA typing. The validity of applying different match criteria based upon the
      molecular weight of a DNA band is discussed. The match criteria presented allow
      visually matching DNA patterns to be confirmed by computer assisted image
      analysis over the entire range of the sizing ladder. Approximately 5000 intragel
      and 5000 intergel comparisons were made between the restriction fragment length
      polymorphism (RFLP) DNA band sizes obtained from casework, mock cases, and
      environmentally insulted samples and the band sizes obtained from their
      corresponding bloodstain standards (controls). Analyses of these data suggested
      that fragments located in different molecular weight size regions of an
      analytical gel required different match criteria for assessing a visual match.
      The results of these analyses support the use of the following match criteria:
      Intragel 0.5-10 kb = +/- 1.7%, 10-15 kb = +/- 3.2%, 15-22.6 kb = +/- 5.8%;
      Intergel and blind control 0.5-10 kb = +/- 3.0%, 10-15 kb = +/- 4.2%, 15-22.6 kb
      = +/- 10.0%; and human cell-line K562 and the monomorphic locus D7Z2 = +/- 2.5%.
      Each match criterion was also evaluated with respect to the distance in
      millimeters between matching bands throughout the 0.5-22.6 kb molecular weight
      size range. Applying these match criteria to different gel regions has been shown
      to be valid and reliable in comparisons conducted on more than 10,000 validation
      samples, in over 500 forensic cases and in more than 200 searches of a criminal
      sexual offender (CSO) database containing over 5000 individuals.

PMID- 8522914
TI  - Genotyping of the DQA1*4 alleles by restriction enzyme digestion of the PCR
      product from the AmpliType PM kit.
AB  - An earlier study has shown that the three DQA1*4 alleles (0401, 0501 and 0601)
      can be distinguished by restriction enzyme digestion of the polymerase chain
      reaction (PCR) product derived from the DQ alpha AmpliType kit (Perikin-Elmer,
      Norwalk, NJ). We have found that the AmpliType PM kit (Perkin-Elmer, Branchburg,
      NJ) can also be used to achieve the same goal. In this case, a Bio-Profil image
      analysis system (Vilber Lourmat, Marne La Vallee, France) is used for evaluating
      the restricted patterns. After typing the six alleles of DQA1 by the AmpliType
      HLA DQ alpha Detection Reagent Set (Perkin-Elmer, Branchburg, NJ), the PCR
      products from the PM kit with allele 4 were digested with Fok I and RsaI,
      separately. Since the other five fragments from PM kit will conceal the digested
      fragments of the HLA DQA1 PCR products, we measured the optical density of the
      pre- and post-digested 242 bp fragments in Fok I digestion, and 214/221 bp
      fragments in Rsa I digestion to decide the results of enzyme digestion. Out of
      136 samples used in this study, 61 contain the DQA1 allele 4 determined by the DQ
      alpha AmpliType method. All 61 were typed with enzyme digestion, of which there
      are 2.3%, 19.8% and 8.1% in allele 0401, 0501 and 0601, respectively. Our
      procedure can thus extend the utilization of AmpliType PM kit and increase the
      discrimination power of the DQA1 system, especially in populations with high
      distribution of allele 4.

PMID- 8522915
TI  - Genetic polymorphism of alpha-2-HS-glycoprotein in northern Bavaria (Germany).
      Simplified AHSG-phenotyping by isoelectric focusing using dry gels.
AB  - A simple and practical method of detecting AHSG using isoelectric focusing on dry
      gels is described. The procedure is both rapid and provides reliable results.
      AHSG phenotypes were determinated in 215 unrelated individuals from Northern
      Bavaria. The allele frequencies obtained were: AHSG*1 = 0.7139, AHSG*2 = 0.2697
      and AHSG*3 = 0.0164.

PMID- 8522916
TI  - Casework experience of GSR detection in Israel, on samples from hands, hair, and
      clothing using an autosearch SEM/EDX system.
AB  - Casework experience in the detection of GSR particles on samples from hands, hair
      and clothing is reported for the period of 6 years (1989-1994). The overall
      "success" rate on the examined samples is about 10%. Aspects of the sampling
      procedures, the number of particles detected per sample and problems of possible
      contamination are discussed.

PMID- 8522917
TI  - Visceral larva migrans induced eosinophilic cardiac pseudotumor: a cause of
      sudden death in a child.
AB  - A case of fatal cardiac larva migrans in a 10-year-old boy is described. The
      autopsy findings were quite dramatic, with a bosselated, sessile polypoid mass
      involving the left ventricular myocardium and protruding into the ventricular
      lumen. The precise morphologic characterization of the zoonotic ascarid larva was
      impaired by advanced resorption of the larva by an inflammatory infiltrate.
      Nonetheless, morphometry of the larval remnants strongly suggested the raccoon
      ascarid, Baylisascaris procyonis, as the causative agent.

PMID- 8522918
TI  - Methamphetamine and amphetamine derived from the metabolism of selegiline.
AB  - Routine methamphetamine testing identified a urine specimen with inconsistent
      screening and confirmation results. The methamphetamine RIA screening test
      (Diagnostic Products Corporation) indicated a borderline positive specimen, while
      the achiral confirmatory GC/MS result showed 4690 ng/mL of methamphetamine and
      1895 ng/mL of amphetamine. Analysis of the specimen after derivatization with S(
      )-N-trifluoroacetylprolyl chloride showed only the presence of 1-amphetamine and
      1-methamphetamine. It was later learned that the individual providing the
      specimen had been taking Selegiline. Selegiline, (-) propynylmethamphetamine, is
      a monoamine oxidase inhibitor used for the treatment of Parkinson's disease. It
      is sold under the trade name Eldepryl. Its major metabolites are 1
      methamphetamine, 1-amphetamine and N-desmethylselegiline. Urine specimens from
      other Selegiline users were obtained and analyzed. A characteristic metabolic
      pattern was noted, exemplified by a ratio of 1-methamphetamine to 1-amphetamine
      of about 2.8. This is in contrast to what is observed in the urine of individuals
      who ingest pure 1-methamphetamine, such as with Vicks Inhaler, where the 1
      methamphetamine to 1-amphetamine ratio in the urine is usually greater than 8.
      Caution is advised when interpreting methamphetamine results without using a
      chiral identification technique.

PMID- 8522920
TI  - Further commentary on Black Talon bullet recovery at autopsy.

PMID- 8522919
TI  - Raped women and HIV infection.

PMID- 8522921
TI  - Commentary on "A suicide by self decapitation," (J Forensic Sci, 38, (4), 981
      984)

PMID- 8522922
TI  - Unintended toxicity (intoxication) by cannabis ingestion of space cake.

PMID- 8522923
TI  - Commentary on Pizzola, P. A., Roth, S., and De Forest, P. R., blood droplet
      dynamics--I. (J Forensic Sci, 31, (1), 36-49), and on Ristenbatt, R. R. and
      Shaler, R. C., A bloodstain pattern interpretation case involving an apparent
      'stomping.' (J Forensic Sci, 40, (1), 139-145)

PMID- 8522924
TI  - Review: autoerotic asphyxiation in the United States.

PMID- 8522925
TI  - A comparative study of genetic variation at five VNTR loci in three ethnic groups
      of Houston, Texas.
AB  - Following the technique of Southern blot restriction fragment length
      polymorphisms (RFLP) analysis, we generated a database of DNA profiles at five
      Variable Number of Tandem Repeats loci (D1S7, D2S44, D4S139, D10S28, and D17S79)
      for 669 individuals of three major ethnic populations (Caucasians, Blacks, and
      Hispanics) of Houston, Texas. Analysis of fragment sizes at these loci within
      each sample, as well as their fixed-bin analyses, reveal that the assumptions of
      independence of allelic occurrences within and between loci are valid for this
      database. Fixed-bin allele frequency tables, therefore, are the best descriptors
      of this database for conservative forensic calculations. Finally, we demonstrate
      that this regional database from Houston, Texas, does not yield any meaningfully
      different forensic inference than the one obtained from the National database of
      the respective ethnic groups.

PMID- 8522926
TI  - Forensic identification of ungulate species using restriction digests of PCR
      amplified mitochondrial DNA.
AB  - A survey of mitochondrial D-loop variation in 15 species of ungulates was
      conducted via amplification by the polymerase chain reaction followed by
      restriction fragment length polymorphism analysis. This survey included moose
      (Alces alces), caribou (Rangifer tarandus), mule deer (Odocoileus hemionus
      hemionus), black-tailed deer (O. h. columbianus), white-tailed deer (O.
      virginianus), waipiti (Cervus elaphus), pronghorn antelope (Antilocapra
      americana), bighorn sheep (Ovis canadensis), Stone's sheep (O. dalli), domestic
      sheep (O. aries), moulflon sheep (O. musimon), mountain goat (Oreamnos
      americanus), domestic goat (Capra hircus), domestic cattle (Bos taurus), and
      bison (Bison bison). The results of this preliminary survey indicate that there
      may be sufficient species specific variation in the D-loop region of the
      mitochondrial genome of the ungulate species examined here, with the exception of
      deer (Odocoileus) species, to establish the species origin of the mitochondrial
      haplotypes of this group. The Odocoileus species are known to hybridize and
      sharing of mtDNA haplotypes was observed. The chelex DNA extraction technique was
      successfully used on small blood stains.

PMID- 8522927
TI  - Investigation of species specificity using nine PCR-based human STR systems.
AB  - Several eukaryotic genomes contain polymorphic markers consisting of trimeric and
      tetrameric short tandem repeats (STR). Recent reports have demonstrated the
      variability of short tandem repeat (STR) polymorphisms at a variety of loci among
      several human population groups. Currently, there are nine commercially available
      STR PCR systems from Promega Corporation that may be utilized for human
      identification. We report here the analysis of 23 different species DNA's using
      these nine STR primer systems to assess their specificity for human euchromatin.
      The STR systems tested include, CSF1PO, TPOX, THO1, HPRTB, FESFPS, vWF and F13A01
      as single systems and as triplex systems (CSF1PO/TPOX/THO1 and HPRTB/FESFPS/vWF).
      There were no STR PCR products observed for seventeen of the twenty-three species
      regardless of the STR system. Amplified STR fragments were detected in rhesus DNA
      for CSF1PO, TPOX and HPRTB systems. STR PCR products were detected for human,
      gorilla, chimpanzee, and orangutan DNAs using eight of the nine systems. FESFPS
      primers did not amplify DNA fragments from any of the species tested. Most of the
      STR PCR products detected from primate DNAs electrophoretically migrated outside
      of the human allelic ladder fragments and as a result, allele designations were
      not possible.

PMID- 8522928
TI  - Arson trend increasing--a real challenge to psychiatry.
AB  - This research evaluated the arson trend in Finland since the 1960s by analyzing
      the Official Crime Statistics of Finland registered by the police and examined
      more detailed about arsonists (n = 98), who had been in the forensic psychiatric
      pretrial examination by using homicide offenders (n = 55) as control subjects.
      From 1965 to 1991 the percentage of arson in relation to all crimes increased
      fivefold and in the same timeframe the amount of arson increased nearly tenfold.
      According to the police in Finland there are committed over 700 arsons every
      year, of which 90% are committed by men. The percentage of women has however
      increased 0.2% yearly. Women today commit about 10% and juveniles 10 to 15% of
      all arsons. The arsonists differed from the homicide offenders regarding rural
      residence (P = 0.009), poor education (P = 0.004), absence of regular work at the
      time of the crime (P = 0.004), suicidality (P = 0.001), alcohol problems (P =
      0.002), psychiatric care (P = 0.000.02) and arsonists more commonly found to be
      not responsible for the crime committed (P = 0.01).

PMID- 8522929
TI  - Postmortem acetaminophen pharmacokinetics: an experimental study of site and time
      dependent concentration changes.
AB  - Postmortem blood drug concentrations are obtained routinely for assessment of the
      cause of mortality. However, the relationship of postmortem drug concentration to
      blood concentrations at the time of death remains poorly characterized. Using
      Ketamine sedation, 10 New Zealand white rabbits were sacrificed 20 minutes after
      oral gavage with liquid acetaminophen 160 mg/kg as a model drug. Blood samples
      were obtained from peripheral (femoral vein) and central sites (heart & inferior
      cava) over time and compared with heart blood concentrations obtained at the time
      of sacrifice. The mean +/- SE antemortem acetaminophen concentration was 63.1 +/-
      14.6 mcg/ml. Postmortem central blood concentrations were as follows: T = 3 h:
      200.8 +/- 129.2 micrograms/mL, T = 6 h: 100.8 +/- 39.6 micrograms/mL and T = 12
      h: 480.8 +/- 128.8 micrograms/mL. Postmortem peripheral site results were: T = 3
      h: 50.2 +/- 21.4 micrograms/mL, T = 6 h: 100.8 +/- 18.1 and T = 12 h: 117.7 +/-
      37.2 micrograms/mL. Overall, blood acetaminophen concentrations increased
      significantly over time for central sampling sites. Drug concentration increases
      seen in the central sampling sites were several times higher than that seen in
      peripheral blood. Blood samples taken from peripheral sites did not alter
      significantly. The results of this controlled study were consistent with previous
      autopsy case series and case reports suggesting that postmortem drug
      concentrations do not reflect premortem values. Variables affecting postmortem
      drug concentrations include both postmortem sampling time and anatomic blood
      collection site.

PMID- 8522930
TI  - Selecting an appropriate isotopic internal standard for gas chromatography/mass
      spectrometry analysis of drugs of abuse--pentobarbital example.
AB  - Internal standards are commonly used for the quantitative determination of drugs
      of abuse and their metabolites (drug/metabolite) in biological fluids and tissues
      by the selective ion monitoring (SIM) gas chromatography/mass spectrometry
      (GC/MS) procedure. Analogs of drugs/metabolites that are labeled with three or
      more deuterium atoms (isotopic analog) at appropriate positions are considered to
      be the most effective internal standards for these applications. Before a
      specific deuterated analog can be adopted as an internal standard in a GC/MS
      assay, the mass spectrum of the compound or its derivative must be evaluated
      along with the corresponding spectrum from the parent drug/metabolite. There
      should be an adequate number of sufficiently high-mass ions (typically three for
      the drug/metabolite and two for the isotopic analog) that can be attributed to
      each analyte, and these ions should be sufficiently free of interference from the
      other analyte of the pair (cross-contribution). Interferences may be caused by
      the presence of an isotopic impurity in the deuterated analog (extrinsic factor)
      or may be due to the ion fragmentation characteristics of the compound (intrinsic
      factor). The extrinsic factor may be corrected by the manufacturer with different
      synthetic methods and purification procedures, while the intrinsic factor may be
      partially or wholly corrected through the use of different chemical derivatives
      (sample preparation stage) or different ionization (GC/MS assay stage)
      procedures. In this study, pentobarbital/d5-pentobarbital is used as the exemplar
      analyte/deuterated analog pair to illustrate the ion selection and evaluation
      procedures. Full-scan mass spectra were employed for preliminary ion selection.
      SIM data were then used to calculate the extent, if any, of cross
      contributions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522931
TI  - In-vitro production of ethanol in urine by fermentation.
AB  - Driving while under the influence of alcohol (DUI) can lead to serious injuries
      to the intoxicated driver and surrounding individuals, in addition to revocation
      or suspension of driving privileges. The accuracy and interpretation of the
      testing procedures may be compromised if an individual's urine contains sugar,
      and either bacteria or yeast. Under these conditions, ethanol can be produced in
      vitro, producing a result that may be erroneously indicative of DUI. In this
      study three yeast species and six bacterial species were added to a blank urine
      sample devoid of any alcohol or sugar. Samples were incubated at 0, 25, and 35
      degrees C for 24, 48, and 144 hours in the presence of one of four different
      sugars. Ethanol concentrations were assayed using an enzymatic alcohol
      dehydrogenase assay. Results showed that when glucose was used as a substrate,
      all yeast species (Candida albicans, Candida parapsilosis, and Candida sp. not
      albicans) and three bacterial species (Klebsiella pneumoniae, Escherichia coli,
      and Proteus mirabilis) were capable of producing ethanol while the other three
      (Enterococcus sp., Staphylococcus sp. not aureus, and Pseudomonas aeruginosa)
      were not. The rate of ethanol production is temperature dependent and can be
      inhibited by storage of samples at 0 degrees C or the use of approximately 1%
      sodium fluoroide as an antimicrobial agent. Many of these species were also able
      to use other substrates (sucrose, fructose, and galactose) to produce ethanol by
      fermentation.

PMID- 8522932
TI  - Crime laboratory proficiency testing results, 1978-1991, I: Identification and
      classification of physical evidence.
AB  - The proficiency testing of crime laboratories began in the mid-1970s and
      presently assumes an important role in quality assurance programs within most
      forensic laboratories. This article reviews the origins and early results of this
      testing program and also examines the progress of proficiency testing in allied
      scientific fields. Beginning in 1978, a fee-based crime laboratory proficiency
      testing program was launched and has grown to its present level involving almost
      400 laboratories worldwide. This is the first of two articles that review the
      objectives, limitations and results of this testing from 1978 through 1991. Part
      I reviews the success of laboratories in the identification and classification of
      common evidence types: controlled substances, flammables, explosives, fibers,
      bloodstains, and hairs. Laboratories enjoy a high degree of success in
      identifying drugs and classifying (typing) bloodstains. They are moderately
      successful in identifying flammables, explosives, and fibers. Animal hair
      identification and human hair body location results are troublesome. The second
      paper will review the proficiency of crime laboratories in determining if two or
      more evidentiary samples shared a common origin.

PMID- 8522933
TI  - Treatment orientation and associated characteristics of North American academic
      psychiatrists.
AB  - We present data showing the degree to which a "biological-psychotherapeutic"
      division persists in American psychiatry, and how psychiatrists' treatment
      orientation is associated with personal and professional characteristics. Almost
      two thirds of academic psychiatrists who responded to our survey (N = 435) could
      be classified as either biological (27%) or psychotherapeutic (37%) in
      orientation, according to the proportion of their caseload to which they provided
      psychotherapy (< or = 25% vs. > 75%). There appears to have been an increase over
      the last 35 years in the proportion of psychiatrists who can be classified as
      biologically oriented and a decrease in the proportion who can be classified as
      psychotherapeutically oriented, as well as the emergence of a large class of
      intermediate or "eclectic" practitioners (36%). Several personal and professional
      attributes were distributed differentially according to treatment orientation.
      Psychotherapeutically oriented respondents more frequently reported personal
      histories of psychiatric disorders than did biologically oriented respondents
      (64% vs. 39%) as well as greater satisfaction with clinical work (81% vs. 53%
      "very satisfied"). Differences were also found in age, gender, history of
      personal psychotherapy, family history of psychiatric disorder, history of
      marijuana use, degrees of involvement in research, teaching and clinical care of
      patients, and overall work satisfaction, as well as other characteristics.

PMID- 8522934
TI  - Does a clerkship affect students' views of psychiatric patients?
AB  - This study deals with the views of medical students toward real psychiatric
      patients. The students answered seven questions about ten patients who had been
      interviewed by a senior faculty member. The interviews were recorded on
      audiovisual tapes. The questions dealt with different aspects of mental illness
      and included views on how laypersons would evaluate and respond to patients, what
      it would be like to care for the patients, and whether the patients were
      potentially dangerous. Answers to questions were correlated. Gender and the
      student's accuracy in rating psychopathology were used as independent variables
      to examine students' views and the possible change in these views as a result of
      participating in a 6-week psychiatric clerkship. The pattern of intercorrelations
      is reported and discussed. Negative views correlated with anticipated difficulty
      in caring for patients, and positive views correlated with a higher accuracy in
      rating psychopathology. In general, student views about mental illness were
      relatively impervious to the effect of a clerkship. Results are discussed in
      terms of prior research and knowledge about gender differences in interpersonal
      sensitivity. Some of the social implications of the results are discussed.

PMID- 8522935
TI  - Insight in clinical psychiatry. A new model.
AB  - Recent interest in insight in psychiatry has resulted in studies focusing on
      correlations between insight and variables such as severity of psychopathology,
      neuropsychological impairments, and magnetic resonance imaging. However, there
      has been relatively little exploration of the concept of insight itself as a
      basis of empirical research. This paper examines the concept of insight,
      differentiating this from the phenomenon of insight, and proposes that insight is
      a construct that needs to be considered from the perspective of the patient, of
      the clinician, and of their interaction. A new hierarchical model of insight
      construction is described, closely linked to symptom formation, and mechanisms
      are suggested to explain insight structure in relation to the different ways
      symptoms arise. The relationship between insight and symptom structure and
      disease suggests that the phenomenon of insight will vary in relation to
      different diseases. This in turn suggests that insight assessments should be
      modified according to the individual disease.

PMID- 8522936
TI  - Insight in schizophrenia and mania.
AB  - We administered a series of 12 brief vignettes depicting examples of positive,
      negative, and manic psychopathology in everyday language to 21 patients with
      schizophrenia and 20 patients with mania. We asked patients to rate, first, how
      similar they were to the individual depicted in each vignette, and, second, the
      degree to which the experiences or behaviors depicted in each vignette reflected
      mental illness. Psychiatrists also rated how similar each patient was to each
      vignette. At admission, patients with schizophrenia rated themselves as
      significantly less similar to the positive symptom vignettes than the
      psychiatrists rated them. Patients with mania did not differ from the
      psychiatrist in rating their similarity to the vignettes, but they strongly
      denied that the vignettes reflected mental illness.

PMID- 8522937
TI  - Anterior brain deficits in chronic alcoholism. Cause or effect?
AB  - To investigate the hypothesis of anterior brain involvement in alcoholism,
      nonfamilial short-term drinkers (STD) and long-term drinkers (LTD) were assessed
      using neuropsychological tests commonly related to frontal lobe functions. Both
      STDs and LTDs were similarly impaired on measures of visually mediated concept
      formation and flexibility of thinking. Results from other time-constrained tests
      that required good concentration and immediate memory, visual scanning, and
      visual-motor coordination were significantly lower in the LTD group as compared
      with STDs. The data suggest a dual-factor hypothesis of anterior cerebral
      dysfunctions in alcoholism: a preexisting deficit in conceptual thinking and
      consequential CNS abnormality (psychomotor slowing, decreased attentiveness, and
      immediate memory) associated with prolonged alcohol intake, and resembling signs
      of premature aging.

PMID- 8522938
TI  - A scale for assessing the stage of substance abuse treatment in persons with
      severe mental illness.
AB  - Substance abuse is common among persons with severe mental illness, but few
      measures exist for clinicians to evaluate treatment progress. The Substance Abuse
      Treatment Scale (SATS) combines a motivational hierarchy with explicit substance
      use criteria to form an eight-stage model of the recovery process. Data are
      presented supporting the reliability and validity of the SATS, based on its use
      in a community-based sample of persons with dual disorders. The SATS can be used
      as either a process or an outcome measure, for individuals or for groups, and its
      value in making explicit the stages of substance abuse treatment is discussed.

PMID- 8522939
TI  - A comparative study of family functioning among Vietnamese and Cambodian
      refugees.
AB  - This study was designed to determine the extent of family problems among a clinic
      population of Cambodian and Vietnamese refugees, and to identify similarities and
      differences between the two groups. All 107 patients with adolescent children
      from a total clinic population of 298 were interviewed using a semistructured
      questionnaire, results were tabulated, and statistical methods were applied. The
      types of problems with children described by parents were classified into the
      dimensions of communication, personal behaviors, school performance, social
      behaviors, and antisocial behaviors. There were significantly more problems
      described by Vietnamese parents as compared with Cambodian parents. Vietnamese
      parents reported significantly more dissatisfaction with life in the United
      States. For both ethnic groups, parents' relationships with their adolescent
      children were a major source of concern and had a major impact on parents'
      perceptions of their own health. Yet, there were important ethnic differences
      between these refugee groups in how patients perceived their problems.

PMID- 8522940
TI  - The role of RNA editing in controlling glutamate receptor channel properties.

PMID- 8522941
TI  - Effects of protein kinase inhibitors on morphology and function of cultured
      bovine adrenal chromaffin cells: KN-62 inhibits secretory function by blocking
      stimulated Ca2+ entry.
AB  - In cultured bovine adrenal chromaffin cells, a nonselective protein kinase
      inhibitor, staurosporine, inhibits secretory function and induces neurite
      outgrowth. In the present study, effects of other nonselective protein kinase
      inhibitors (K-252a, H-7, and H-8) and reportedly selective protein kinase
      inhibitors (KN-62 and chelerythrine chloride) were examined on bovine adrenal
      chromaffin cell morphology, secretory function, and 45Ca2+ uptake. Treatment of
      chromaffin cells with 10 microM K-252a, 50 microM H-7, or 50 microM H-8 induced
      changes in cell morphology within 3 h; these compounds also induced a time
      dependent inhibition of stimulated catecholamine release. Chelerythrine chloride,
      a selective inhibitor of Ca2+/phospholipid-dependent protein kinase, did not
      induce outgrowth or inhibit secretory function under our treatment conditions. KN
      62, a selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK
      II), significantly inhibited stimulated catecholamine release (IC50 value of 0.32
      microM), but had no effect on cell morphology. The reduction of secretory
      function induced by 1 microM KN-62 was significant within 5 min and rapidly
      reversible. Unlike H-7, H-8, and staurosporine, KN-62 significantly inhibited
      stimulated 45Ca2+ uptake. KN-04, a structural analogue of KN-62 that does not
      inhibit CaMK II, inhibited stimulated 45Ca2+ uptake and catecholamine release
      like KN-62. These studies indicate that KN-62 inhibits secretory function via the
      direct blockade of activated Ca2+ influx. The nonselective inhibitors, K-252a, H
      7, H-8, and staurosporine, inhibit secretory function by another mechanism,
      perhaps one involving alterations in the cytoskeleton.

PMID- 8522942
TI  - Overexpression of alternative human acetylcholinesterase forms modulates process
      extensions in cultured glioma cells.
AB  - In addition to its well-known synaptic function, acetylcholinesterase was
      recently shown to stimulate neurite outgrowth from cultured chick neurons in a
      manner unrelated to its catalytic activity. It remained unclear, however, whether
      each of the variant acetylcholinesterase enzyme forms can promote such process
      extension and whether this effect of acetylcholinesterase was limited to neurite
      outgrowth. Using DNA microinjections and stable transfections of cultured glioma
      cells, we explored the possibility that specific acetylcholinesterase isoforms
      affect cellular development and morphology of CNS astrocytes. Cells microinjected
      with human ACHEDNA constructs that differ in their exon-intron composition
      displayed rapid yet stable induction of cell body enlargement and process
      extensions. Cells transfected with ACHEDNA carrying the neuronal-characteristic
      3'-E6 domain also displayed stable process extensions. However, stable
      transfections with ACHEDNAs including the 3'-alternative 14/E5 region induced the
      appearance of small, round cells in a dominant manner. This was associated with
      expression of 14/E5-ACHEmRNA transcripts and the production of soluble
      acetylcholinesterase monomers that were catalytically indistinguishable from the
      3'-E6 enzyme but displayed higher electrophoretic mobility than that of the 3'-E6
      form. Thus, variable expression levels and alternative splicing modes of the ACHE
      gene correlated in these experiments with glial development in a manner that was
      apparently unrelated to catalysis.

PMID- 8522943
TI  - Nerve growth factor, epidermal growth factor, and insulin differentially
      potentiate ATP-induced [Ca2+]i rise and dopamine secretion in PC12 cells.
AB  - To study how growth factors affect stimulus-secretion coupling pathways, we
      examined the effects of nerve growth factor (NGF), epidermal growth factor (EGF),
      and insulin on ATP-induced [Ca2+]i rise and dopamine secretion in PC12 cells.
      After a 4-day incubation of cells, all three factors increased ATP-induced
      dopamine secretion significantly. We then examined which step of ATP-induced
      secretion was affected by the growth factors. Cellular levels of dopamine-beta
      hydroxylase and catecholamines were increased by NGF treatment but were not
      affected by EGF or insulin. The ATP-induced [Ca2+]i rise was also enhanced after
      growth factor treatment. The EC50 of ATP for inducing [Ca2+]i rise and dopamine
      secretion was increased by NGF treatment but not by treatment with EGF or
      insulin. Accordingly, the dependence on [Ca2+]i of dopamine secretion was
      increased significantly only in NGF-treated cells. Our results suggest that for
      EGF- and insulin-treated PC12 cells, the increase in secretion is mainly due to
      increased potency of ATP in inducing [Ca2+]i rise. NGF treatment not only
      increased the potency of ATP but also decreased the Ca2+ sensitivity of the
      secretory pathway, which as a result becomes more tightly regulated by changes in
      [Ca2+]i.

PMID- 8522944
TI  - Evidence that nitric oxide causes calcium-independent release of [3H] dopamine
      from rat striatum in vitro.
AB  - Nitric oxide (NO), liberated from the photoactive donor Roussin's black salt
      (RBS), was investigated for its ability to release tritium from [3H]dopamine
      loaded rat striatal slices. Our results show that illumination of RBS-pretreated
      striatal slices caused an increase in basal dopamine release, which was reduced
      by approximately 73% in the presence of oxyhaemoglobin (10 microM), indicating
      that it was mediated by liberation of NO. The release was insensitive to removal
      of extracellular calcium yet was not due to gross cellular damage of the tissue,
      as there was no detectable increase in lactate dehydrogenase release. Chelation
      of intracellular calcium with 1,2-bis(o-amino-phenoxy)ethane-N,N,N',N'
      tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM; 10 microM) had no effect
      on the dopamine release stimulated by illumination of RBS-pretreated slices. The
      concentration of BAPTA-AM was adequate to chelate intracellular calcium because
      it inhibited release evoked by the calcium ionophore ionomycin (10 microM).
      Superfusion with zaprinast (10 microM) had no effect on RBS-induced dopamine
      release, suggesting that a mechanism independent of cyclic GMP is involved. This
      study indicates that NO has a stimulatory effect on striatal dopamine release in
      vitro that is independent of calcium.

PMID- 8522945
TI  - Induction of adrenal tyrosine hydroxylase mRNA by single immobilization stress
      occurs even after splanchnic transection and in the presence of cholinergic
      antagonists.
AB  - Immobilization (IMO) stress elevates plasma catecholamines and increases tyrosine
      hydroxylase (TH) gene expression in rat adrenals. This study examined the
      mechanism(s) of IMO-induced changes in adrenal TH mRNA levels. Innervation of the
      adrenal medulla is predominantly cholinergic and splanchnicotomy as well as
      nicotinic receptor antagonists prevent the cold-induced rise in TH mRNA levels.
      In this study, the IMO-induced rise in plasma catecholamines, but not TH mRNA
      levels, was reduced by the antagonist chlorisondamine. Muscarinic antagonist
      atropine also did not prevent the IMO stress-elicited rise in TH mRNA.
      Furthermore, denervation of the adrenals by unilateral splanchnicotomy did not
      block the IMO-induced rise in TH mRNA but completely prevented the induction of
      neuropeptide Y mRNA. These results suggest that (1) the large increase in adrenal
      TH gene expression elicited by a single IMO stress is not regulated via
      cholinergic receptors or splanchnic innervation, and (2) there is a dissociation
      between regulatory mechanisms of catecholamine secretion and elevation of TH gene
      expression in the adrenal medulla of rats during IMO stress.

PMID- 8522946
TI  - Alternate promoters in the rat aromatic L-amino acid decarboxylase gene for
      neuronal and nonneuronal expression: an in situ hybridization study.
AB  - Aromatic L-amino acid decarboxylase (AADC) is found in both neuronal cells and
      nonneuronal cells, and a single gene encodes rat AADC in both neuronal and
      nonneuronal tissues. However, two cDNAs for this enzyme have been identified: one
      from the liver and the other from pheochromocytoma. Exons 1a and 1b are found in
      the liver cDNA and the pheochromocytoma cDNA, respectively. In the third exon
      (exon 2), there are two alternatively utilized splicing acceptors specific to
      these exons, 1a and 1b. Structural analysis of the rat AADC gene showed that both
      alternative promoter usage and alternative splicing are operative for the
      differential expression of this gene. To demonstrate whether alternative promoter
      usage and splicing are tissue specific and whether the exons 1a and 1b are
      differentially and specifically transcribed in nonneuronal and neuronal cells,
      respectively, in situ hybridization histochemistry for the rat brain, adrenal
      gland, liver, and kidney was carried out using these two exon probes. The exon 1a
      probe specifically identified AADC mRNA only in nonneuronal cells, including the
      liver and kidney, and the exon 1b probe localized AADC mRNA to monoaminergic
      neurons in the CNS and the adrenal medulla. Thus, both alternative promoter usage
      and differential splicing are in fact operative for the tissue-specific
      expression of the rat AADC gene.

PMID- 8522947
TI  - Arachidonate 5-lipoxygenase and its activating protein: prominent hippocampal
      expression and role in somatostatin signaling.
AB  - 5-Lipoxygenase-activating protein (FLAP) is an 18-kDa integral membrane protein
      required, in peripheral cells, for the activation of 5-lipoxygenase (5-LO) and
      for the resulting synthesis of leukotrienes from arachidonic acid. In the brain,
      the leukotrienes have been implicated in several pathophysiological events and in
      the electrophysiological effect of somatostatin, yet the cellular origin and role
      of these messenger molecules are still poorly understood. In the present study,
      we used reverse transcriptase-polymerase chain reaction, in situ hybridization,
      and immunohistochemistry to demonstrate that 5-LO and FLAP are expressed in
      various regions of the rat brain, including hippocampus, cerebellum, primary
      olfactory cortex, superficial neocortex, thalamus, hypothalamus, and brainstem.
      Highest levels of expression were observed in cerebellum and hippocampus. In the
      latter we demonstrate the colocalization of 5-LO and FLAP in CA1 pyramidal
      neurons. Moreover, electrophysiological experiments show that selective
      inhibition of FLAP with the compound MK-886 (0.25-1 microM) prevents the
      somatostatin-induced augmentation of the hippocampal K+ M-current. Our results
      provide necessary evidence for the presence and signaling role of 5-LO and FLAP
      in central neurons and strongly support their proposed participation in
      somatostatin-receptor transmembrane signaling.

PMID- 8522948
TI  - Homocysteate-evoked release of acetylcholine from the rabbit retina.
AB  - The cholinergic amacrine cells of the rabbit retina can be labeled with
      [3H]choline and the activity of the cholinergic population monitored by following
      the release of [3H]acetylcholine. It has been proposed that L-homocysteate may be
      the main endogenous transmitter released onto cholinergic amacrine cells by
      bipolar cells. Therefore, we have examined the effects of the isomers of
      homocysteate on the release of [3H]acetylcholine. In magnesium-free medium, D
      homocysteate was slightly more potent than the L-isomer. The addition of
      magnesium, which blocks responses mediated by NMDA receptors, preferentially
      reduced but did not eliminate, the response to L-homocysteate. 2-Amino-7
      phosphonoheptanoate, a potent NMDA antagonist, preferentially blocked L
      homocysteate evoked responses. 6,7-Dinitroquinoxaline-2,3-dione, a potent kainate
      antagonist, preferentially blocked D-homocysteate-evoked responses. Therefore, in
      the rabbit retina, L-homocysteate is an NMDA-preferring agonist, whereas D
      homocysteate is a kainate-preferring agonist. In addition, we found that L
      homocysteate can activate the physiologically activated kainate receptor but only
      when used in millimolar concentrations and under conditions that minimize NMDA
      receptor activation. However, the low potency of L-homocysteate combined with low
      affinity for the glutamate transporter, lack of immunocytochemical localization
      in bipolar cells, and low retinal content place serious limitations on the role
      of L-homocysteate at the bipolar-to-cholinergic amacrine cell synapse.

PMID- 8522949
TI  - Characterization of the glutamate receptors mediating release of somatostatin
      from cultured hippocampal neurons.
AB  - L-Glutamate, NMDA, DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA), and kainate (KA) increased the release of somatostatin-like
      immunoreactivity (SRIF-LI) from primary cultures of rat hippocampal neurons. In
      Mg(2+)-containing medium, the maximal effects (reached at approximately 100
      microM) amounted to 737% (KA), 722% (glutamate), 488% (NMDA), and 374% (AMPA);
      the apparent affinities were 22 microM (AMPA), 39 microM (glutamate), 41 microM
      (KA), and 70 microM (NMDA). The metabotropic receptor agonist trans-1
      aminocyclopentane-1,3-dicarboxylate did not affect SRIF-LI release. The release
      evoked by glutamate (100 microM) was abolished by 10 microM dizocilpine (MK-801)
      plus 30 microM 1-aminophenyl-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine
      (GYKI 52466). Moreover, the maximal effect of glutamate was mimicked by a mixture
      of NMDA+AMPA. The release elicited by NMDA was sensitive to MK-801 but
      insensitive to GYKI 52466. The AMPA- and KA-evoked releases were blocked by 6,7
      dinitroquinoxaline-2,3-dione (DNQX) or by GYKI 52466 but were insensitive to MK
      801. The release of SRIF-LI elicited by all four agonists was Ca(2+) dependent,
      whereas only the NMDA-evoked release was prevented by tetrodotoxin. Removal of
      Mg2+ caused increase of basal SRIF-LI release, an effect abolished by MK-801.
      Thus, glutamate can stimulate somatostatin release through ionotropic NMDA and
      AMPA/KA receptors. Receptors of the KA type (AMPA insensitive) or metabotropic
      receptors appear not to be involved.

PMID- 8522950
TI  - Potassium-induced stimulation of glutamate uptake in mouse cerebral astrocytes:
      the role of intracellular pH.
AB  - The Na(+)-glutamate cotransporters are believed to countertransport OH- and K+.
      Previous evidence that the velocity of glutamate uptake can exceed the acid
      extrusion capacity of astrocytes raised the question of whether intracellular pH
      can become rate limiting for glutamate uptake. Cytoplasmic buffering capacity and
      acid extrusion in astrocytes are partially HCO3- dependent. Also, it was reported
      recently that raising extracellular [K+] alkalinizes astrocyte cytoplasm by an
      HCO3- dependent mechanism. Here, we have compared glutamate uptake in HCO3(-)
      buffered and HCO3(-)-depleted solutions at varying [K+]. We observed a pronounced
      stimulation of glutamate uptake by extracellular K+ (3-24 mM) that was
      substantially HCO3- dependent and affected preferentially the uptake of high
      concentrations (> 25 microM) of glutamate. Stimulation of uptake by low
      extracellular [K+] (1.5-3 mM) was less dependent on HCO3-. Potassium-induced
      stimulation of uptake was weaker in rat astrocyte cultures than in mouse. The
      effects of Ba2+ and amiloride on glutamate uptake, as well as the HCO3(-)
      dependent stimulatory effects of K+ and the species difference, all related
      consistently to effects on intracellular pH. The effects on uptake, however, were
      much larger than predicted by the associated changes in electrochemical gradient
      of OH-. A "bimodal" scheme for glutamate transport can account qualitatively for
      the observed correlation between intracellular pH and velocity of glutamate
      uptake.

PMID- 8522951
TI  - Arachidonic acid and oleoylacetylglycerol induce a synergistic facilitation of
      Ca(2+)-dependent glutamate release from hippocampal mossy fiber nerve endings.
AB  - Arachidonic acid and oleoylacetylglycerol enhance depolarization-evoked glutamate
      release from hippocampal mossy fiber nerve endings. It was proposed this is a
      Ca(2+)-dependent effect and that protein kinase C is involved. Here we report
      that arachidonic acid and oleoylacetylglycerol synergistically potentiate the
      glutamate release induced by the Ca2+ ionophore ionomycin. The Ca2+ dependence of
      this effect was established, as removal of Ca2+ eliminated evoked release and the
      lipid-dependent potentiation. Also, Ca2+ channel blockers attenuated ionomycin-
      and KCl-evoked exocytosis, as well as the facilitating effects of the lipid
      mediators. Although facilitation required Ca2+, it may not involve an enhancement
      of evoked Ca2+ accumulation, because ionomycin-dependent glutamate release was
      potentiated under conditions that did not increase ionomycin-induced Ca2+
      accumulation. Also, the facilitation may not depend on inhibition of K+ efflux,
      because enhanced release was observed in the presence of increasing
      concentrations of 4-aminopyridine and diazoxide did not reduce the lipid
      dependent potentiation of exocytosis. In contrast, disruption of cytoskeleton
      organization with cytochalasin D occluded the lipid-dependent facilitations of
      both KCl- and ionomycin-evoked glutamate release. In addition, arachidonic acid
      plus glutamatergic or cholinergic agonists enhanced glutamate release, whereas a
      role for protein kinase C in the potentiation of exocytosis was substantiated
      using kinase inhibitors. It appears that the lipid-dependent facilitation of
      glutamate release from mossy fiber nerve endings requires Ca2+ and involves
      multiple presynaptic effects, some of which depend on protein kinase C.

PMID- 8522952
TI  - Muscarinic receptor sequestration in SH-SY5Y neuroblastoma cells is inhibited
      when clathrin distribution is perturbed.
AB  - The possibility that clathrin plays a role in the agonist-mediated sequestration
      of muscarinic cholinergic receptors in human SH-SY5Y neuroblastoma cells has been
      investigated by the application of experimental paradigms previously established
      to perturb clathrin distribution and receptor cycling events. Preincubation of SH
      SY5Y cells under hypertonic conditions resulted in a pronounced inhibition of
      agonist-induced muscarinic receptor sequestration (70-80% at 550 mOsm), which was
      reversed when cells were returned to isotonic medium. Depletion of intracellular
      K+ or acidification of the cytosol also resulted in > 80% inhibition of
      muscarinic receptor sequestration. Under conditions of hypertonicity, depletion
      of intracellular K+, or acidification of cytosol, muscarinic receptor-stimulated
      phosphoinositide hydrolysis and Ca2+ signaling events were either unaffected or
      markedly less inhibited than receptor sequestration. That these same experimental
      conditions did perturb clathrin distribution was verified by immunofluorescence
      studies. Hypertonicity and depletion of intracellular K+ resulted in a pronounced
      accumulation of clathrin in the perinuclear region, whereas acidification of the
      cytosol resulted in the appearance of microaggregates of clathrin throughout the
      cytoplasm and at the plasma membrane. The results are consistent with the
      possibility that muscarinic receptors in SH-SY5Y cells are endocytosed via a
      clathrin-dependent mechanism.

PMID- 8522953
TI  - Calcium ion impedes translation initiation at the synapse.
AB  - Stimulation of synaptoneurosome suspensions by the neurotransmitter glutamate
      gives rise to rapid loading of ribosomes onto mRNA and increased incorporation of
      amino acids into trichloroacetic acid-precipitable polypeptides. Metabotropic
      glutamate receptors (mGluRs) are responsible for this effect. Although
      simultaneous Ca2+ entry and mGluR stimulation do not change the response, entry
      of Ca2+ 30 s or 3 min before mGluR stimulation markedly depresses the
      polyribosomal loading. Either NMDA or ionophore (A23187) produces the depression.
      A calmodulin antagonist, W7, alleviates the effect, suggesting that inactivation
      of phospholipase A2 by calcium-calmodulin-dependent kinase II is partially
      responsible for the phenomenon. Thus, interaction between different classes of
      glutamate receptors affects the control of protein translation at the synapse.
      This effect may partially explain recent observations of negative interactions
      between receptor classes in induction of long-term potentiation.

PMID- 8522954
TI  - 3.6 kb of the 5' flanking DNA activates the mouse tyrosine hydroxylase gene
      promoter without catecholaminergic-specific expression.
AB  - The tyrosine hydroxylase (TH) gene is expressed exclusively in cells and neurons
      that synthesize and release L-DOPA or catecholamines. To further understand the
      molecular genetic mechanisms that regulate this cell-type specific expression, a
      chimeric gene was prepared by linking 3.6 kb of the 5' flanking DNA of the mouse
      TH gene, including the +1 initiation site for transcription, to an E. coli beta
      galactosidase reporter. This fusion gene (TH3.6LAC) was used to prepare
      transgenic mice, and the tissue distribution of expression of TH3.6LAC was
      determined by the measurement of beta-galactosidase enzymatic activity and/or by
      the detection of the transcription product of the chimeric gene by RNase
      protection assays. In two separate founder lines, TH3.6LAC expression was
      observed in every region of the brain that was examined, including the olfactory
      bulb, brainstem, cerebellum, diencephalon, hippocampus, striatum, and cerebral
      cortex. Expression of TH3.6LAC was observed in the adrenal gland of one founder
      line but not in the other. TH3.6LAC activation was undetectable in peripheral
      organs that were examined, including the liver, heart, salivary gland, kidney,
      lung, and spleen. Although 3.6 kb of the 5' regulatory DNA of the mouse TH gene
      is sufficient to activate the TH fusion gene in the mouse, it is not enough to
      restrict its expression to catecholaminergic cells.

PMID- 8522955
TI  - Serotonin 5-HT1D and 5-HT1A receptors respectively mediate inhibition of
      glutamate release and inhibition of cyclic GMP production in rat cerebellum in
      vitro.
AB  - The K(+)-evoked overflow of endogenous glutamate from cerebellar synaptosomes was
      inhibited by serotonin [5-hydroxytryptamine (5-HT); pD2 = 8.95], 8-hydroxy-2-(di
      n- propylamino)tetralin (8-OH-DPAT; pD2 = 7.35), and sumatriptan (pD2 = 8.43).
      These inhibitions were prevented by the selective 5-HT1D receptor antagonist N-[4
      methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1, 2,4 -
      oxadiazol-3-yl) (1,1-biphenyl)-4-carboxamide (GR-127935). The three agonists
      tested also inhibited the cyclic GMP (cGMP) response provoked in slices by K+
      depolarization; pD2 values were 9.37 (5-HT), 9.00 (8-OH-DPAT), and 8.39
      (sumatriptan). When cGMP formation was elevated by directly activating glutamate
      receptors with NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA), the inhibition of the cGMP responses displayed the following pattern: 5
      HT (pD2 values of 8.68 and 8.72 against NMDA and AMPA, respectively); 8-OH-DPAT
      (respective pD2 values of 9.15 and 9.00); sumatriptan (0.1 microM) was
      ineffective. The 5-HT1A receptor antagonist (S)-(+)N-tert-butyl-3-[4-(2-
      methoxyphenyl)piperazin-1-yl]-2-phenylpropionamide dihydrochloride [(+)-WAY
      100135] did not prevent the inhibition of glutamate release by 5-HT but blocked
      the inhibition by 8-OH-DPAT of the NMDA/AMPA-evoked cGMP responses. It is
      suggested that presynaptic 5-HT1D receptors mediate inhibition directly of
      glutamate release and indirectly of the cGMP responses to the released glutamate;
      on the other hand, activation of (postsynaptic) 5-HT1A receptors causes
      inhibition of the cGMP responses linked to stimulation of NMDA/AMPA receptors.

PMID- 8522956
TI  - Serotonin enhances striatal dopamine outflow in vivo through dopamine uptake
      sites.
AB  - Serotonin (5-HT) administered at 1, 3, and 10 microM into the striatum of
      halothane-anesthetized rats by in vivo microdialysis increased extracellular
      dopamine (DA) in a concentration-dependent manner (approximately 65, 190, and
      440%, respectively). These effects were reduced by 50% in the presence of 1
      microM tetrodotoxin (TTX) or in the absence of Ca2+ ions. The DA uptake blocker
      nomifensine (0.1 microM) significantly lowered (by 50%) the enhancement of DA
      outflow induced by 3 microM 5-HT. Nomifensine (1 microM) coperfused with 1 microM
      TTX abolished the 1 and 3 microM 5-HT-induced DA outflow, whereas the effect of
      10 microM 5-HT was significantly reduced by 1 (-55%) and 10 micro M (-70%)
      nomifensine. These data demonstrate that, in vivo, striatal DA uptake sites are
      partially involved in the DA-releasing action of 5-HT.

PMID- 8522957
TI  - Nicotine effects on dopamine clearance in rat nucleus accumbens.
AB  - In vivo voltammetry was used to measure the clearance to exogenously applied
      dopamine (DA) in the nucleus accumbens following acute systemic nicotine
      administration in urethane-anesthetized rats. The IVEC-5 system was used for
      continuous in vivo electrochemical measurements. A finite amount of DA was
      pressure-ejected (25-100 nl, 200 microM barrel concentration) at 5-min intervals
      from micropipettes (tip diameter, 10-15 microns) positioned 250 +/- 50 microns
      from the recording electrode. The peak DA concentration after each DA ejection
      was significantly decreased in rats following nicotine, but not in rats given
      saline. In addition, when mecamylamine was administered 20 min before nicotine it
      clearly antagonized nicotine effects. These results suggest that nicotine may
      actually facilitate DA transporter systems within the nucleus accumbens.

PMID- 8522958
TI  - Dopaminergic inhibition of catecholamine secretion from chromaffin cells:
      evidence that inhibition is mediated by D4 and D5 dopamine receptors.
AB  - Previous studies have suggested that activation of D2-like dopamine receptors
      inhibits catecholamine secretion from adrenal chromaffin cells. The purpose of
      this study was to determine whether the activation of D1-like receptors on
      chromaffin cells affects either catecholamine release from the cells or the
      inhibition of secretion by D2-like dopamine receptors. Both D1- and D2-selective
      agonists inhibited secretion elicited by dimethylphenylpiperazinium (DMPP),
      veratridine, and high K+ levels. The D1-selective agonists 6-chloro-7,8-dihydroxy
      3-allyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (CI-APB) and SKF-38393
      inhibited DMPP-stimulated catecholamine secretion in a concentration-dependent
      manner; 50% inhibition was obtained with approximately 10 microM CI-APB and
      approximately 100 microM SKF-38393. Of the D2-selective agonists, bromocriptine
      was a more potent inhibitor of DMPP-stimulated catecholamine release than was
      quinpirole. The inhibition of secretion caused by CI-APB or SKF-38393 was
      additive with the inhibition caused by bromocriptine. Pertussis toxin treatment
      (50 ng/ml, 18 h) attenuated the inhibitory effect of D2-selective, but not D1
      selective, dopamine agonists. In addition, forskolin-stimulated adenylyl cyclase
      activity was inhibited by D2-selective, but not D1-selective, agonists. Neither
      D1- nor D2-selective agonists stimulated adenylyl cyclase activity in the cells,
      although cyclase activity was stimulated by forskolin, carbachol, and vasoactive
      intestinal peptide. DMPP-stimulated Ca2+ uptake was inhibited by both D1- and D2
      selective dopamine agonists. PCR analysis was used to determine which of the
      dopamine receptor subtypes within the D1-like and D2-like subfamilies was
      responsible for the observed inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522959
TI  - GABAA receptors modulate early spontaneous excitatory activity in differentiating
      P19 neurons.
AB  - P19 embryonic carcinoma (EC) stem cells are pluripotent and are efficiently
      induced to differentiate into neurons and glia with retinoic acid (RA) treatment.
      Within 5 days, a substantial number of differentiating P19 cells express gene
      products that are characteristic of a neuronal phenotype. P19 neurons were used
      as a model to explore the relationship between neuronal "differentiation" in
      vitro and the acquisition of gamma-aminobutyric acid (GABAA) receptors and
      functional GABA responses. Pulse-labeling experiments using bromodeoxyuridine
      indicated that all neurons had become postmitotic within 3-4 days after treatment
      with RA. This was confirmed by a reduction in the immunocytochemical detection of
      the undifferentiated stem cell antigen SSEA-1. Subsequently, a transient
      expression of nestin was observed during the first 5 days in vitro (DIV) after
      exposure to RA. By 5-10 DIV after RA, a significant number of neurons
      (approximately 80-90%) expressed immunocytochemically detectable glutamate
      decarboxylase and GABA coincident with the acquisition of membrane binding sites
      for tetanus toxin. These phenotypic markers were maintained for > 30 DIV after
      RA. Under current-clamp conditions, random, low-amplitude, spontaneous electrical
      activity appeared in neurons within the first few days after RA treatment and
      this was blocked by the specific GABAA receptor antagonist bicuculline.
      Thereafter, the appearance and progressive increases in the frequency of
      spontaneous action potentials in P19 neurons were observed that were similarly
      attenuated by bicuculline. In neurons > 5 DIV after RA, exogenous application of
      GABA elicited similar action potentials. The onset of excitatory responses to
      GABA or muscimol in voltage-clamped neurons appeared immediately after the
      cessation of neuronal mitosis and before the previously reported acquisition of
      responses to glutamate. In fura-2 imaging studies, the exogenous application of
      GABA resulted in neuron-specific increases in intracellular Ca2+. Thus, P19
      neurons provide an in vitro model for the study of the early acquisition and
      properties of electrical excitability to GABA and the expression of functional
      GABAA receptors.

PMID- 8522960
TI  - Carrier-mediated release of serotonin by 3,4-methylenedioxymethamphetamine:
      implications for serotonin-dopamine interactions.
AB  - In vivo microdialysis was used to determine whether the 3,4
      methylenedioxymethamphetamine (MDMA)-induced release of serotonin (5-HT) in vivo
      involves a carrier-mediated process and to investigate further the state
      dependent interaction between 5-HT and dopamine. MDMA produced a dose-dependent
      increase in the extracellular concentration of 5-HT in the striatum and
      prefrontal cortex that was attenuated by treatment with fluoxetine but not by
      tetrodotoxin. Suppression by fluoxetine of the MDMA-induced release of 5-HT was
      accompanied by a suppression of the MDMA-induced release of dopamine.
      Administration of MDMA to rats treated with carbidopa and L-5-hydroxytryptophan
      resulted in a synergistic elevation of the extracellular concentration of 5-HT
      that was much greater than that produced by either treatment alone. The MDMA
      induced release of dopamine by MDMA also was potentiated in 5-hydroxytryptophan
      treated rats. These data are consistent with the view that MDMA increases the
      extracellular concentration of 5-HT by facilitating carrier-mediated 5-HT
      release, which can be enhanced greatly under conditions in which 5-HT synthesis
      is stimulated. Moreover, these data are supportive of a state-dependent,
      stimulatory role of 5-HT in the regulation of dopamine release.

PMID- 8522961
TI  - Thiamine, thiamine phosphates, and their metabolizing enzymes in human brain.
AB  - Total thiamine (the sum of thiamine and its phosphate esters) concentrations are
      two- to fourfold lower in human brain than in the brain of other mammals. There
      were no differences in the total thiamine content between biopsied and autopsied
      human brain, except that in the latter, thiamine triphosphate was undetectable.
      The main thiamine phosphate-metabolizing enzymes could be detected in autopsied
      brain, and the kinetic parameters were comparable to those reported in other
      species. Thiamine diphosphate levels were lowest in hippocampus (15 +/- 4 pmol/mg
      of protein) and highest in mammillary bodies (24 +/- 4 pmol/mg of protein).
      Maximal levels of thiamine and its phosphate ester were found to be present at
      birth. In parietal cortex and globus pallidus, mean levels of total thiamine in
      the oldest age group (77-103 years) were, respectively, 21 and 26% lower than
      those in the middle age group (40-55 years). Unlike cerebral cortex, the globus
      pallidus showed a sharp drop in thiamine diphosphate levels during infancy, with
      concentrations in the oldest group being only approximately 50% of the levels
      present during the first 4 months of life. These data, consistent with previous
      observations conducted in blood, suggest a tendency toward decreased thiamine
      status in older people.

PMID- 8522962
TI  - Assessment of amyloid beta protein in cerebrospinal fluid as an aid in the
      diagnosis of Alzheimer's disease.
AB  - The principal constituent of amyloid plaques found in the brains of individuals
      with Alzheimer's disease (AD) is a 39-42-amino-acid protein, amyloid beta protein
      (A beta). This study examined whether the measurement of A beta levels in CSF has
      diagnostic value. There were 108 subjects enrolled in this prospective study: AD
      (n = 39), non-AD controls (dementing diseases/syndromes; n = 20), and other (n =
      49). CSF was obtained by lumbar puncture, and A beta concentrations were
      determined using a dual monoclonal antibody immunoradiometric sandwich assay. The
      mean A beta value for the AD group (15.9 +/- 6.8 ng/ml) was not significantly
      different from that for the non-AD control group (13.0 +/- 7.1 ng/ml; p = 0.07),
      and substantial overlap in results were observed. A beta values did not correlate
      with age (r = -0.05, p = 0.59), severity of cognitive impairment (r = 0.22, p =
      0.21), or duration of AD symptoms (r = 0.14, p = 0.45). These findings are in
      conflict with other reports in the literature; discrepant results could be due to
      the instability of A beta in CSF. A beta immunoreactivity decays rapidly under
      certain conditions, particularly multiple freeze/thaw cycles. Use of a
      stabilizing sample treatment buffer at the time of lumbar puncture allows storage
      of CSF without loss of A beta reactivity. In conclusion, the total CSF A beta
      level is not a useful marker for current diagnosis of AD.

PMID- 8522963
TI  - Heterogeneity in the expression pattern of two ganglioside synthase genes during
      mouse brain development.
AB  - Gangliosides are synthesized by sequential catalytic reaction of multiple
      glycosyltransferases. GM2/GD2 synthase and GD3 synthase are key enzymes for
      ganglioside synthesis, because their relative activities regulate the main
      profiles of ganglioside expression. Mouse GD3 synthase (EC 2.4.99.8) cDNA was
      cloned by eukaryotic expression cloning, and its mRNA expression as well as that
      of GM2/GD2 synthase gene during the development of the mouse CNS was analyzed by
      using northern blotting, reverse transcription-polymerase chain reaction, and in
      situ hybridization. When brain tissue was analyzed as a whole mass, a typical
      pattern corresponding to the reported findings obtained by biochemical analyses
      was observed, i.e., high expression of GD3 synthase gene in the early stage and
      gradual increase of GM2/GD2 synthase gene expression in the late stage of the
      development. However, the results of in situ hybridization of these two genes
      revealed that the expression kinetics of these two genes were heterogeneous among
      various sites in the brain under development. These findings suggest that various
      expression patterns of the two genes reflect differences in the course of the
      development of individual sites, and also different ganglioside components are
      required in individual portions of the brain for development and maintenance of
      the function.

PMID- 8522964
TI  - Intracellular calcium dynamics and cellular energetics in ischemic NG108-15 cells
      studied by concurrent 31P/19F and 23Na double-quantum filtered NMR spectroscopy.
AB  - The role of voltage-sensitive Ca2+ channels in mediating Ca2+ influx during
      ischemia was investigated in NG108-15 cells, a neuronal cell line that does not
      express glutamate-sensitive receptor-mediated Ca2+ channels. Concurrent 31P/19F
      and 23Na double-quantum filtered (DQF) NMR spectra were used to monitor cellular
      energy status, intracellular [Ca2+] ([Ca2+]i), and intracellular Na+ content in
      cells loaded with the calcium indicator 1,2-bis-(2-amino-5-fluorophenoxy)ethane
      N,N,N',N'-tetraacetic acid (5FBAPTA) during ischemia and reperfusion. Cells
      loaded with 5FBAPTA were indistinguishable from unloaded cells except for small
      immediate decreases in levels of phosphocreatine (PCr) and ATP. Ischemia induced
      a steady decrease in intracellular pH and PCr and ATP levels, and a steady
      increase in intracellular Na+ content; however, a substantial increase in [Ca2+]i
      (about threefold) was seen only following marked impairment of cellular energy
      status, when PCr was undetectable and ATP content was reduced to 55% of control
      levels. A depolarization-induced increase in [Ca2+]i could be completely blocked
      by 1 microM nifedipine, whereas up to 20 microM nifedipine had no effect on the
      increase in [Ca2+]i seen during ischemia. These data demonstrate that voltage
      gated Ca2+ channels do not mediate significant Ca2+ flux during ischemia in this
      cell line and suggest an important role for Ca2+i stores, the Na+/Ca2+
      antiporter, or other processes linked to cellular energy status in the increase
      in cytosolic Ca2+ level during ischemia.

PMID- 8522965
TI  - Lipid composition in scrapie-infected mouse brain: prion infection increases the
      levels of dolichyl phosphate and ubiquinone.
AB  - The neutral and phospholipid composition of mouse brain infected with scrapie
      prions was investigated. During the later stages of this disease, the level of
      dolichol decreased by 30% whereas the level of dolichyl phosphate increased by
      30%. In terminally ill mice, there was also a 2.5-fold increase in both total
      ubiquinone and its reduced form. Furthermore, alpha-tocopherol was elevated at
      this stage by 50%. In contrast, no changes were observed in phospholipid amount,
      in phospholipid composition, and in phosphatidylethanolamine plasmalogen content
      during the entire disease process. The fatty acid and aldehyde composition of
      individual phospholipids remained unaltered as well. No modifications could be
      detected in cholesterol content. Thus, the majority of membrane lipids in scrapie
      infected mouse brain are modified in neither quantity nor structure, but specific
      changes occur to a few polyisoprenoid lipids. This specificity indicates that,
      although prions accumulate in lysosomes, the infection process is not associated
      with a general membrane destruction caused by lysosomal enzyme leakage.

PMID- 8522966
TI  - Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit
      spinal cord.
AB  - The microtubule-associated protein tau plays an important role in the dynamics of
      microtubule assembly necessary for axonal growth and neurite plasticity. Ischemia
      disrupts the neuronal cytoskeleton both by promoting proteolysis of its
      components and by affecting kinase and phosphatase activities that alter its
      assembly. In this study the effect of ischemia and reperfusion on the expression
      and phosphorylation of tau was examined in a reversible model of spinal cord
      ischemia in rabbits. tau was found to be dephosphorylated in response to ischemia
      with a time course that closely matched the production of permanent paraplegia.
      Dephosphorylation of tau was limited to the caudal lumbar spinal cord. In a
      similar manner, Ca2+/calmodulin-dependent kinase II activity was reduced only in
      the ischemic region. Thus, dephosphorylation of tau is an early marker of
      ischemia as is the rapid loss of Ca2+/calmodulin-dependent kinase II activity.
      tau, however, was rephosphorylated rapidly during reperfusion at site(s) that
      cause a reduction in its electrophoretic mobility regardless of the neurological
      outcome. Alterations in phosphorylation or degradation of tau may affect
      microtubule stability, possibly contributing to disruption of axonal transport
      but also facilitating neurite plasticity in a regenerative response.

PMID- 8522967
TI  - Quinolinic acid levels in a murine retrovirus-induced immunodeficiency syndrome.
AB  - Mice infected with the retrovirus mixture designated LP-BM5 murine leukemia virus
      (MuLV) develop an immunosuppressive disease. Quinolinic acid (QUIN) is an
      endogenous neurotoxic N-methyl-D-aspartate agonist that may contribute to the
      pathogenesis of HIV-associated neurologic disease. In the present study, the
      levels of QUIN in brain and blood were measured in mice infected with LP-BM5 MuLV
      and compared with those in uninfected mice and mice infected with the
      nonpathogenic strain of ecotropic MuLV (helper component of LP-BM5 MuLV).
      Infection with LP-BM5 MuLV resulted in progressive increases in blood QUIN levels
      beginning 2 weeks after inoculation that peaked by 16 weeks postinfection. QUIN
      levels were also increased in cerebral cortex, hippocampus, and striatum. In
      systemic tissues, QUIN levels were increased in lung, liver, and spleen. In
      contrast, infection with the ecotropic viral component of the LP-BM5 MuLV mixture
      was not associated with any changes in brain, blood, or systemic tissue QUIN
      levels, even though helper virus burdens were comparable to those in mice
      infected with LP-BM5 MuLV. Treatment of LP-BM5 MuLV-infected mice with the
      antiretroviral agent zidovudine (azidothymidine) significantly reduced blood and
      brain QUIN levels in association with reductions in viral load in brain and
      spleen. These observations suggest that elevated QUIN production is not
      attributable to productive infection with retrovirus per se but occurs in
      response to an agent or agents, such as cytokines, that are produced by the host
      in response to virus infection.

PMID- 8522968
TI  - Complement regulatory molecules on human myelin and glial cells: differential
      expression affects the deposition of activated complement proteins.
AB  - The expression of decay-accelerating factor CD55, membrane cofactor protein CD46,
      and CD59 was studied on Schwann cells cultured from human sural nerve and myelin
      membranes prepared from human cauda equina and spinal cord. These proteins are
      regulatory membrane molecules of the complement system. CD55 and CD46 are
      inhibitors of C3 and C5 convertases and CD59 inhibits C8 and C9 incorporation
      into C5b-9 complex and C9-C9 polymerization. The presence of these proteins was
      assessed by using antibodies to each of the proteins by fluorescent microscopy,
      fluorescence-activated cell sorter analysis, and also sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and western blot analysis. Schwann cells in
      culture expressed CD55, CD46, and CD59. It is interesting that only CD59 was
      detected on myelin from both central and peripheral nerve tissue. The ability of
      these proteins to limit C3 peptide deposition and C9 polymerization in myelin was
      studied by western blot analysis. C3b deposition was readily detected on antibody
      sensitized myelin incubated with normal human serum used as a source of
      complement but not with EDTA-treated or heat-inactivated serum. C3b deposition
      was not affected by anti-CD55 antibody. On the other hand, poly-C9 formation in
      myelin, which was maximum when 50% normal human serum was used, was increased
      four-to fivefold when myelin was preincubated with anti-CD59. Our data suggest
      that complement activation on myelin is down-regulated at the step of the
      assembly of terminal complement complexes, including C5b-9, due to the presence
      of CD59.

PMID- 8522969
TI  - Effects of chronic ethanol consumption on sterol transfer proteins in mouse
      brain.
AB  - Although lipids are essential to brain function, almost nothing is known of lipid
      transfer proteins in the brain. Early reports indicates cross-reactivity of brain
      proteins with antisera against two native liver sterol transfer proteins, sterol
      carrier protein-2 (SCP-2) and the liver form of fatty acid-binding protein (L
      FABP). Herein, polyclonal antibodies raised against the recombinant liver sterol
      transfer proteins SCP-2 and L-FABP were used to identify the lipid transfer
      proteins in the brains of alcohol-treated and control mice. L-FABP was not
      detectable in brain of either control or chronic ethanol-treated mice. In
      contrast, SCP-2 not only was present, but its level was significantly (p < 0.05)
      increased 23 and 50%, respectively, in brain homogenates and synaptosomes of mice
      exposed to alcohol. To determine whether antibodies against the recombinant liver
      SCP-2 reflected true levels of SCP-2 in brain, the cDNA sequence for brain SCP-2
      was isolated from a brain cDNA library. The mouse brain SCP-2 sequence was 99.99%
      identical to the mouse liver SCP-2 sequence. The translated sequence differed by
      only one amino acid, and the replacement was conservative. Thus, unlike the fatty
      acid binding proteins, the SCP-2 moieties of brain and liver are essentially
      identical. Polyclonal antibodies against acyl-CoA binding protein, a lipid
      binding protein that does not bind or transfer sterol, showed that increased
      levels of brain SCP-2 with chronic ethanol consumption did not represent a
      general increase in content of all lipid transfer proteins. Changes in the amount
      of SCP-2 may contribute to membrane tolerance to ethanol.

PMID- 8522970
TI  - Various isoforms of myomodulin identified from the male copulatory organ of
      Lymnaea show overlapping yet distinct modulatory effects on the penis muscle.
AB  - Male copulatory behavior in the snail Lymnaea stagnalis is controlled by several
      types of peptidergic neurons, including a cluster of neurons in the ventral lobe
      of the right cerebral ganglion that show immunoreactivity to myomodulin-A of
      Aplysia and innervate the penis complex. We identified structurally myomodulin-A
      and three related peptides from Lymnaea and showed that they are present in a
      characteristic ratio in both the penis nerve and penis complex, suggesting that
      they are processed from a single precursor and transported from the ventral lobe
      to the penis complex. All four peptides decreased the relaxation time of
      electrically evoked contractions of the penis retractor muscle. However, their
      effects on the amplitude of contraction were different, ranging from no effect to
      an increase or a decrease in the amplitude. A mixture of the peptides in a ratio
      as determined by direct mass spectrometry of the penis nerve decreased the
      contraction time, the relaxation time, and the amplitude. These effects resemble
      those of one particular peptide in the mixture. The direct mass spectrometry
      determinations of the peptide profile in the penis nerve suggest that many more,
      as yet unidentified, neuropeptides are involved in modulation of muscle
      activities of the penis complex.

PMID- 8522971
TI  - Tissue distribution and immunocytochemical localization of neurotrophin-3 in the
      brain and peripheral tissues of rats.
AB  - The tissue distribution of neurotrophin-3 (NT-3) was investigated in rats at 1
      month of age using a newly established, sensitive two-site enzyme immunoassay
      system for NT-3, as well as the immunocytochemical localization of this protein.
      The immunoassay for NT-3 enabled us to quantify NT-3 at levels > 3 pg per assay.
      In the rat brain, NT-3 was detectable only in the olfactory bulb (0.54 ng/g wet
      weight), cerebellum (0.71 ng/g), septum (0.91 ng/g), and hippocampus (6.3 ng/g).
      By contrast, NT-3 was widely distributed in peripheral tissues. Appreciable
      levels of NT-3 were also found in the thymus (31 ng/g), heart (38 ng/g),
      diaphragm (21 ng/g), liver (45 ng/g), pancreas (892 ng/g), spleen (133 ng/g),
      kidney (40 ng/g), and adrenal gland (46 ng/g). An antibody specific for NT-3
      bound to pyramidal cells in the CA2-CA4 regions of the hippocampus, to A cells in
      the islets of Langerhans in the pancreas, to unidentified cells in the red pulp
      of the spleen, to liver cells, and to muscle fibers in the diaphragm from rats at
      1 month of age. Molecular masses of NT-3-immunoreactive proteins in the
      hippocampus and pancreas were 14 and 12 kDa, respectively. Thus, in rats, NT-3
      was detected in restricted regions of the brain and in the visceral targets of
      the nodose ganglia at high concentrations. Our present results suggest that NT-3
      not only functions as a classical target-derived neurotrophic factor but also can
      play other roles.

PMID- 8522972
TI  - Effects of rumpshaker mutation on CNS myelin composition and structure.
AB  - Myelinated CNS tissues from homozygous/hemizygous and heterozygous jimpy
      rumpshaker jprsh mutant mice were examined to determine the consequences on
      myelin structure of this mutation in the proteolipid protein (PLP) gene.
      Polyacrylamide gel electrophoresis and immunoblotting of brain homogenates
      confirmed that there was a decrease in PLP levels on the B6C3 genetic background
      onto which this gene was bred. We also observed an increase in level of a protein
      band that could correspond to the uncharacterized 10-kDa PLP previously reported
      in jprsh mice on an Rb(1.3) 1Bnr background. High-performance TLC and
      densitometry of lipids from brain homogenate and isolated myelin revealed a
      decrease in content of cerebrosides and sulfatides. Electron microscopy on optic
      nerves revealed that normal radial component is retained in jprsh myelin, further
      substantiating that PLP is not a component of this junctional complex. X-ray
      diffraction measurements on unfixed optic nerves showed that the jprsh period is
      5-10 A larger than normal. Moreover, jprsh optic nerve myelin was unstable, as
      evidenced by a continual increase in the period postdissection. jprsh myelin that
      was equilibrated at varying pH and ionic strength typically had a larger than
      normal period under all conditions (both swelling and compacting). Our findings
      thus demonstrate that the biochemical abnormalities in the jprsh mutant correlate
      with a wider periodicity and less stable packing of the myelin.

PMID- 8522973
TI  - Inhibition of excitatory amino acid-induced phosphoinositide hydrolysis as a
      possible mechanism of nitroprusside neurotoxicity.
AB  - Inclusion of sodium nitroprusside (Na2[Fe(2+)-(CN)5NO]) into the culture medium
      is toxic to cultured rat cerebellar granule neurons. A possible underlying
      mechanism may be the inhibition of phosphoinositide (PI) response to excitatory
      amino acids (EAAs) because activation of glutamate receptors can be
      neuroprotective and neurotrophic in differentiating neurons. Sodium nitroprusside
      selectively inhibited the PI response to EAAs (NMDA > glutamate = quisqualate >
      kainate) without affecting that to carbachol or KCl. In contrast, S-nitroso-N
      acetyl-penicillamine (SNAP), another nitric oxide (NO) donor, potentiated NMDA
      induced PI hydrolysis. Hemoglobin reversed the effects of nitroprusside and SNAP.
      However, NO may not be involved because NO solution was without effect and N
      acetylpenicillamine, a SNAP analogue that does not contain a NO moiety, also
      potentiated NMDA-induced PI hydrolysis in a hemoglobin-sensitive manner.
      Furthermore, the metabolites of NO (nitrate and nitrite), L-arginine, reduced
      glutathione, 8-bromo-cyclic guanosine 3':5'-cyclic monophosphate (8-Br-cGMP), and
      atrial natriuretic peptide, which accelerates the production of cGMP independent
      of NO, were ineffective as modulators. However, potassium ferrocyanide
      (K4[Fe2+(CN)6]), but not potassium ferricyanide (K3[Fe3+(CN)6]), inhibited NMDA
      induced PI hydrolysis as effectively as nitroprusside, but this inhibition was
      not reversed by hemoglobin. Cyanide, a product from the disintegration of
      nitroprusside, potentiated rather than inhibited NMDA-induced PI hydrolysis.
      Taken together, these results suggest that the parent molecule itself,
      nitroprusside, contributes primarily in inhibiting EAA-induced PI hydrolysis.
      Inhibition of EAA-induced PI hydrolysis may in part mediate the mechanisms of
      nitroprusside toxicity in primary cultures of differentiating cerebellar granule
      neurons.

PMID- 8522974
TI  - Identification of evolutionary conserved regulatory sequences in the 5'
      untranscribed region of the neural-specific ubiquitin C-terminal hydrolase
      (PGP9.5) gene.
AB  - The structure at the 5' end of the gene encoding neural-specific protein gene
      product 9.5 (PGP9.5) has been compared between two evolutionary distant species:
      the human and Monodelphis domestica. In contrast to the highly conserved coding
      sequences of the gene, only a 48% identity was found across a 1-kb stretch of 5'
      untranslated and untranscribed DNA. Promoter function studies performed on the
      human sequence identified a 233-bp CpG-rich minimal promoter. Truncation
      mutagenesis revealed the presence of essential positive cis-acting regulatory
      sequences within the region -182 to -123 relative to the transcription initiation
      site. Sequence alignment analysis of the human and Monodelphis promoter sequences
      showed 76% identity in this 59-bp region of the gene. A perfectly conserved 12-bp
      sequence (PSN) located within this region acts as a non-cell-specific activator
      of transcription in a heterologous reporter gene (pBLCAT2). PGP9.5 gene
      expression can be readily detected in human neuroblastoma cell lines but is
      absent in nonneuronal cell lines such as HeLa. Studies on the cell type
      specificity of the human PGP9.5 promoter demonstrated that in contrast to the
      endogenous gene, the promoter is active in HeLa cells. However, the promoter
      displays higher levels of activity in human neuroblastoma cell lines. A conserved
      16-bp sequence located at -356 (motif 5) was able to reduce the activity of a
      heterologous minimal promoter specifically in HeLa cells. In conclusion, we have
      shown that expression of the PGP9.5 gene is regulated by evolutionary conserved
      positive and negative cis-acting sequences located in the untranscribed region of
      the gene.

PMID- 8522975
TI  - Direct measurement of lipid hydroperoxides in iron-dependent spinal neuronal
      injury.
AB  - The relationship between iron-dependent fetal mouse spinal cord neuron injury and
      the generation of endogenous lipid hydroperoxides (LOOHs) has been investigated.
      Cultured spinal cord neurons were incubated with ferrous iron (3-200 microM).
      Cell viability was measured in terms of the uptake of alpha-[methyl
      3H]aminoisobutyric acid ([3H]AIB). Both endogenously and iron-generated LOOH,
      i.e., free fatty acid hydroperoxide (FFAOOH), phosphatidylethanolamine
      hydroperoxide (PEOOH), and phosphatidylcholine hydroperoxide (PCOOH), were
      measured directly by an HPLC-chemiluminescence (HPLC-CL) assay. The FFAOOH,
      PEOOH, and PCOOH levels in neurons incubated with 200 microM Fe2+ for 40 min
      were, respectively, 22-, 158-, and sevenfold higher than those in non-iron
      exposed cultures, demonstrating that phosphatidylethanolamine (PE) was most
      sensitive to peroxidation. The dose-response and time course of Fe(2+)-induced
      generation of these LOOHs were also established. In both experiments, the LOOH
      levels were correlated directly with loss of neuronal viability, suggesting
      strongly a direct relationship between lipid peroxidation and cell injury. On
      examination of the time course of the LOOH generation, an immediate increase in
      PEOOH and PCOOH levels with only 30 s of Fe2+ incubation was observed. In
      contrast, a lag phase in the increase in FFAOOH level (2 min after Fe2+ addition)
      suggested a delay in the activation of phospholipase A2 (PLA2) required for the
      hydrolysis and generation of FFAOOH. This culture system provides an excellent
      model for screening antioxidant neuroprotective compounds with regard to their
      ability to protect against iron-dependent peroxidative injury and the
      relationship of the neuroprotection to inhibition of lipid peroxidation and/or
      PLA2.

PMID- 8522976
TI  - Characterization and expression of the human A2a adenosine receptor gene.
AB  - The actions of the neurotransmitter adenosine are mediated by a family of high
      affinity, G protein-coupled receptors. We have characterized the gene for the
      human A2a subtype of adenosine receptor (hA2aR) and determined levels of A2aR
      mRNA in human brain regions and nonneural tissues. Human genomic Southern blot
      analysis demonstrates the presence of a single gene encoding the hA2aR located on
      chromosome 22. Two overlapping cosmids containing the hA2aR gene were isolated
      from a chromosome 22 library and characterized. Southern blot and sequence
      analyses demonstrate that the hA2aR gene spans approximately 9-10 kb with a
      single intron interrupting the coding sequence between the regions encoding
      transmembrane domains III and IV. The sequence of the hA2aR gene diverged from
      the reported cDNA structure in the 5' untranslated region. This divergence
      appears to result from an artifact in the construction of the original cDNA
      library. By northern blot analysis, high expression of the hA2aR gene was
      identified in the caudate nucleus with low levels of expression in other brain
      regions. High expression was also seen in immune tissues; lesser A2aR expression
      was detected in heart and lung. The gene for the A2a subtype of receptor for the
      neurotransmitter adenosine falls in the class of intron containing G protein
      coupled receptor genes. Expression in the basal ganglia is consistent with a role
      for the hA2aR in motor control. Activation of the A2aR may also regulate immune
      responses and cardiopulmonary function.

PMID- 8522977
TI  - Characterization of agonist-induced down-regulation of NMDA receptors in
      cerebellar granule cell cultures.
AB  - Exposure of cerebellar granule cells to NMDA in culture at 5 days in vitro, when
      cells are not yet vulnerable to NMDA, evoked a pronounced reduction in NMDA
      receptor activity, measured by NMDA-induced 45Ca2+ influx, and counteracted the
      normal developmental increase in NMDA receptors. The effect was concentration and
      time dependent, the half-maximal effect being reached at about 45 microM and by 4
      5 h. The decrease in NMDA receptor function was accompanied by a significant
      reduction in the protein level of the obligatory NMDA receptor subunit (NR) NR1.
      Both parameters remained at a low level as long as the agonist was present.
      However, receptor down-regulation was reversible, as receptor protein levels and
      NMDA responses were restored to control values upon NMDA removal, this process
      requiring protein synthesis. NMDA treatment also elicited a decrease in NR1,
      NR2A, and NR2B subunit messenger RNA (mRNA) levels. However, in comparison with
      NMDA receptor proteins, the decrease was faster, and NMDA receptor mRNA content
      recovered to control levels within 24 h in spite of the presence of NMDA.
      Concerning the mechanisms of agonist-induced regulation of NMDA receptor
      expression, it seems that protein kinase C-mediated protein phosphorylation is
      not involved, whereas inhibition of Ca2+/calmodulin-dependent kinase II/IV by KN
      62 does depress NMDA receptor expression even in the absence of NMDA.

PMID- 8522978
TI  - Astrocyte leucine metabolism: significance of branched-chain amino acid
      transamination.
AB  - We studied astrocytic metabolism of leucine, which in brain is a major donor of
      nitrogen for the synthesis of glutamate and glutamine. The uptake of leucine into
      glia was rapid, with a Vmax of 53.6 +/- 3.2 nmol/mg of protein/min and a Km of
      449.2 +/- 94.9 microM. Virtually all leucine transport was found to be Na+
      independent. Astrocytic accumulation of leucine was much greater (3x) in the
      presence of alpha-aminooxyacetic acid (5 mM), an inhibitor of transamination
      reactions, suggesting that the glia rapidly transaminate leucine to alpha
      ketoisocaproic acid (KIC), which they then release into the extracellular fluid.
      This inference was confirmed by the direct measurement of KIC release to the
      medium when astrocytes were incubated with leucine. Approximately 70% of the
      leucine that the glia cleared from the medium was released as the keto acid. The
      apparent Km for leucine conversion to extracellular KIC was a medium [leucine] of
      58 microM with a Vmax of approximately 2.0 nmol/mg of protein/min. The
      transamination of leucine is bidirectional (leucine+alpha
      ketoglutarate<==>KIC+glutamate) in astrocytes, but flux from leucine-->glutamate
      is more active than that from glutamate-->leucine. These data underscore the
      significance of leucine handling to overall brain nitrogen metabolism. The
      release of KIC from glia to the extracellular fluid may afford a mechanism for
      the "buffering" of glutamate in neurons, which would consume this
      neurotransmitter in the course of reaminating KIC to leucine.

PMID- 8522979
TI  - Exogenous glutamate concentration regulates the metabolic fate of glutamate in
      astrocytes.
AB  - The metabolic fate of glutamate in astrocytes has been controversial since
      several studies reported > 80% of glutamate was metabolized to glutamine;
      however, other studies have shown that half of the glutamate was metabolized via
      the tricarboxylic acid (TCA) cycle and half converted to glutamine. Studies were
      initiated to determine the metabolic fate of increasing concentrations of [U-13C]
      glutamate in primary cultures of cerebral cortical astrocytes from rat brain.
      When astrocytes from rat brain were incubated with 0.1 mM [U-13C] glutamate 85%
      of the 13C metabolized was converted to glutamine. The formation of [1,2,3-13C3]
      glutamate demonstrated metabolism of the labeled glutamate via the TCA cycle.
      When astrocytes were incubated with 0.2-0.5 mM glutamate, 13C from glutamate was
      also incorporated into intracellular aspartate and into lactate that was released
      into the media. The amount of [13C] lactate was essentially unchanged within the
      range of 0.2-0.5 mM glutamate, whereas the amount of [13C] aspartate continued to
      increase in parallel with the increase in glutamate concentration. The amount of
      glutamate metabolized via the TCA cycle progressively increased from 15.3 to
      42.7% as the extracellular glutamate concentration increased from 0.1 to 0.5 mM,
      suggesting that the concentration of glutamate is a major factor determining the
      metabolic fate of glutamate in astrocytes. Previous studies using glutamate
      concentrations from 0.01 to 0.5 mM and astrocytes from both rat and mouse brain
      are consistent with these findings.

PMID- 8522980
TI  - Investigation of the role of conserved serine residues in the long form of the
      rat D2 dopamine receptor using site-directed mutagenesis.
AB  - Three serine residues (Ser193, Ser194, Ser197) in the fifth transmembrane
      spanning region of the D2 dopamine receptor have been mutated separately to
      alanine and the effects of the mutations determined in ligand-binding experiments
      with [3H] spiperone. For many antagonists the mutations had little effect,
      showing that the overall conformation of the mutant receptors was similar to that
      of the native, although there were effects on the binding of certain antagonists.
      The effect of the mutations on agonist binding to the free receptor (uncoupled
      from G proteins) was determined in the presence of GTP (100 microM). This showed
      that there was no single mode of binding of catecholamine agonists to the
      receptor and that all three serine residues can participate in the binding of
      some agonists, possibly through hydrogen bonds to the catechol hydroxyl groups.
      Coupling of the mutant receptors to G proteins was assessed from agonist-binding
      curves in the absence of GTP, when higher and lower affinity agonist-binding
      sites were seen. Receptor/G protein coupling was generally unaffected by the
      Ala193 and Ala194 mutations, but the Ala197 mutation eliminated receptor/G
      protein coupling for some agonists. These data show that the interactions of
      agonists with the free and coupled forms of the receptor are different.

PMID- 8522981
TI  - A reevaluation of the role of mitochondria in neuronal Ca2+ homeostasis.
AB  - The ability of mitochondrial Ca2+ transport to limit the elevation in free
      cytoplasmic Ca2+ concentration in neurones following an imposed Ca2+ load is
      reexamined. Cultured cerebellar granule cells were monitored by digital fura-2
      imaging. Following KCl depolarization, addition of the protonophore
      carbonylcyanide m-chlorophenylhydrazone (CCCP) to depolarize mitochondria
      released a pool of Ca2+ into the cytoplasm in both somata and neurites. No CCCP
      releasable pool was found in nondepolarized cells. Although the KCl-evoked
      somatic and neurite Ca2+ concentration elevations were enhanced when CCCP was
      present during KCl depolarization, this was associated with a collapsed ATP/ADP
      ratio. In the presence of the ATP synthase inhibitor oligomycin, glycolysis
      maintained high ATP/ADP ratios for at least 10 min. The further addition of the
      mitochondrial complex I inhibitor rotenone led to a collapse of the mitochondrial
      membrane potential, monitored by rhodamine-123, but had no effect on ATP/ADP
      ratios. In the presence of rotenone/oligomycin, no CCCP-releasable pool was found
      subsequent to KCl depolarization, consistent with the abolition of mitochondrial
      Ca2+ transport; however, paradoxically the KCl-evoked Ca2+ elevation is
      decreased. It is concluded that the CCCP-induced increase in cytoplasmic Ca2+
      response to KCl is due to inhibition of nonmitochondrial ATP-dependent transport
      and that mitochondrial Ca2+ transport enhances entry of Ca2+, perhaps by removing
      the cation from cytoplasmic sites responsible for feedback inhibition of voltage
      activated Ca2+ channel activity.

PMID- 8522982
TI  - Localization of sites in the tail domain of the middle molecular mass
      neurofilament subunit phosphorylated by a neurofilament-associated kinase and by
      casein kinase I.
AB  - We have shown previously that a neurofilament (NF)-associated kinase (NFAK)
      extracted from chicken NF preparations phosphorylates selectively the middle
      molecular mass NF subunit (NF-M). Here we show that the major kinase activity in
      NFAK is indistinguishable from enzymes of the casein kinase I (CKl) family based
      on the following criteria: (1) inhibition of NFAK phosphorylation by the
      selective CKl inhibitor CKl-7, (2) the similarity in substrate specificity of
      NFAK and authentic CKl, (3) the correspondence of two-dimensional phosphopeptide
      maps of NF-M phosphorylated in vitro by NFAK with those generated by CKl under
      similar conditions, and (4) immunological cross-reactivity of NFAK with an
      antibody raised against CKl. We have also identified Ser502, SER528, and Ser536
      as phosphorylation sites by NFAK/CKl in vitro, each of which is also
      phosphorylated in vivo. All three serines are found in peptides with CKl
      phosphorylation consensus sequences, and Ser528 and Ser536 and flanking amino
      acids are highly conserved in higher vertebrate NF-M sequences. Neither Ser502
      nor Ser536 has been identified previously as NF-M phosphorylation sites.

PMID- 8522983
TI  - Brain mu-calpain autolysis during global cerebral ischemia.
AB  - Proteolytic degradation of numerous calpain substrates, including cytoskeletal
      and regulatory proteins, has been observed during brain ischemia and reperfusion.
      In addition, calpain inhibitors have been shown to decrease degradation of these
      proteins and decrease postischemic neuronal death. Although these observations
      support the inference of a role for mu-calpain in the pathophysiology of ischemic
      neuronal injury, the evidence is indirect. A direct indicator of mu-calpain
      proteolytic activity is autolysis of its 80-kDa catalytic subunit, and therefore
      we examined the mu-calpain catalytic subunit for evidence of autolysis during
      cerebral ischemia. Rabbit brain homogenates obtained after 0, 5, 10, and 20 min
      of cardiac arrest were electrophoresed and immunoblotted with a monoclonal
      antibody specific to the mu-calpain catalytic subunit. In nonischemic brain
      homogenates the antibody identified an 80-kDa band, which migrated identically
      with purified mu-calpain, and faint 78- and 76-kDa bands, which represent
      autolyzed forms of the 80-kDa subunit. The average density of the 80-kDa band
      decreased by 25 +/- 4 (p = 0.008) and 28 +/- 9% (p = 0.004) after 10 and 20 min
      of cardiac arrest, respectively, whereas the average density of the 78-kDa band
      increased by 111 +/- 50% (p = 0.02) after 20 min of cardiac arrest. No
      significant change in the density of the 76-kDa band was detected. These results
      provide direct evidence for autolysis of brain mu-calpain during cerebral
      ischemia. Further work is needed to characterize the extent, duration, and
      localization of mu-calpain activity during brain ischemia and reperfusion as well
      as its role in the causal pathway of postischemic neuronal injury.

PMID- 8522984
TI  - Interleukin-1 beta-mediated regulation of mu-opioid receptor mRNA in primary
      astrocyte-enriched cultures.
AB  - Opioids have been found to modulate the immune system by regulating the function
      of immunocompetent cells. Several studies suggest that the interaction between
      immune and opioid systems is not unidirectional, but rather reciprocal, in
      nature. In the CNS, one cellular target of immune system activation is the
      astrocytes. These glial cells have been shown to produce the opioid peptide,
      proenkephalin, to express the mu-, delta-, and kappa-opioid receptors, and to
      respond to the immune factor interleukin-1 beta (IL1 beta) with an increased
      proenkephalin synthesis. To characterize more completely the astrocytic opioid
      response to immune factor stimulation, we examined the effect of IL1 beta (1
      ng/ml) on the mu-receptor mRNA expression in primary astrocyte-enriched cultures
      derived from rat (postnatal day 1-2) cortex, striatum, cerebellum, hippocampus,
      and hypothalamus. A 24-h treatment with IL1 beta produced a 70-80% increase in
      the mu-receptor mRNA expression in the striatal, cerebellar, and hippocampal
      cultures but had no effect on this expression in the cortical and hypothalamic
      cultures. This observation represents one of the few demonstrated increases in
      levels of the mu-receptor mRNA in vitro or in vivo, since the cloning of the
      receptor. The enhanced mu-receptor mRNA expression, together with the previous
      observation that IL1 beta stimulates proenkephalin synthesis in astrocytes,
      supports the IL1 beta-mediated regulation of an astroglial opioid peptide and
      receptor in vitro, a phenomenon that may be significant in the modulation of the
      gliotic response to neuronal damage. Therefore, the astroglial opioid "system"
      may be important in the IL1 beta-initiated, coordinated response to CNS
      infection, trauma, or injury.

PMID- 8522985
TI  - Electroconvulsive seizure increases the expression of CREM (cyclic AMP response
      element modulator) and ICER (inducible cyclic AMP early repressor) in rat brain.
AB  - Rapid expression of ICER (inducible cyclic AMP early repressor), an inducible
      member of the CREM (cyclic AMP response element modulator) family of
      transcription factors, has been reported in neuroendocrine tissues and cell
      lines, but not in brain. In the present study, we demonstrate that acute electro
      convulsive seizure (ECS) increases the expression of ICER in several rat brain
      regions. RNase protection analysis demonstrated that 1-2 h after administration
      of ECS, levels of mRNA for ICER and a splice variant, ICER gamma, were
      significantly increased in hippocampus, frontal cortex, and cerebellum. It is
      surprising that ECS also increased levels of mRNA for several CREM isoforms that
      previous studies have reported were not rapidly inducible. In situ hybridization
      analysis confirmed these findings and demonstrated that ECS induction of ICER was
      most obvious in the dentate gyrus granule cell layer of hippocampus and deep
      layers of cerebral cortex. Induction of ICER and CREM was accompanied by
      increased expression of two small CRE-binding complexes. Gel supershift analysis
      with CREM/ICER antisera confirmed that the inducible CRE-binding complexes
      contain CREM/ICER. Induction of CREM and ICER may contribute to negative feedback
      regulation of gene transcription that is increased by acute seizure and
      activation of CREB (cyclic AMP response element-binding protein.

PMID- 8522986
TI  - Increased brain levels of platelet-activating factor in a murine acquired immune
      deficiency syndrome are NMDA receptor-mediated.
AB  - Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an
      immunodeficiency syndrome (murine AIDS) and an encephalopathy characterized by
      impaired spatial learning and memory. Because platelet-activating factor (PAF)
      has been implicated in the pathogenesis of HIV-associated dementia complex, brain
      PAF levels were measured in LP-BM5 MuLV-infected mice. PAF levels in cerebral
      cortex and hippocampus were significantly increased at 6 and 12 weeks after LP
      BM5 MuLV inoculation, whereas significant increases in striatal and cerebellar
      PAF levels were observed only at 12 weeks after inoculation. Administration of
      the NMDA antagonist MK-801 significantly reduced the increased PAF levels in the
      cerebral cortex and hippocampus of LP-BM5 MuLV-infected mice. These results
      indicate that the LP-BM5 MuLV-induced increases in brain PAF levels are the
      results of NMDA receptor activation and are consistent with the hypothesis that
      elevated CNS PAF levels contribute to the behavioral deficits observed in LP-BM5
      MuLV-infected mice.

PMID- 8522987
TI  - Mechanism of enhancement of rat brain serotonin synthesis by acute fluoxetine
      administration.

PMID- 8522988
TI  - Cloning, characterization, and chromosomal localization of a human 5-HT6
      serotonin receptor.
AB  - We describe the cloning and characterization of a human 5-HT6 serotonin receptor.
      The open reading frame is interrupted by two introns in positions corresponding
      to the third cytoplasmic loop and the third extracellular loop. The human 5-HT6
      cDNA encodes a 440-amino-acid polypeptide whose sequence diverges significantly
      from that published for the rat 5-HT6 receptor. Resequencing of the rat cDNA
      revealed a sequencing error producing a frame shift within the open reading
      frame. The human 5-HT6 amino acid sequence is 89% similar to the corrected rat
      sequence. The recombinant human 5-HT6 receptor is positively coupled to adenylyl
      cyclase and has pharmacological properties similar to the rat receptor with high
      affinity for several typical and atypical antipsychotics, including clozapine.
      The receptor is expressed in several human brain regions, most prominently in the
      caudate nucleus. The gene for the receptor maps to the human chromosome region
      1p35-p36. This localization overlaps that established for the serotonin 5-HT1D
      alpha receptor, suggesting that these may be closely linked. Comparison of
      genomic and cDNA clones for the human 5-HT6 receptor also reveals an Rsal
      restriction fragment length polymorphism within the coding region.

PMID- 8522989
TI  - Overexpression of Ca2+/calmodulin-dependent protein kinase II inhibits neurite
      outgrowth of PC12 cells.
AB  - To investigate the physiological role of Ca2+/calmodulin-dependent protein kinase
      II (CaM kinase II) in neuronal differentiation, we transfected the cDNA of the
      alpha subunit of mouse CaM kinase II (CaM kinase II alpha) into PC12 cells and
      established clonal cell lines that constitutively express the transfected CaM
      kinase II alpha gene. The expression of CaM kinase II alpha was confirmed by
      northern blot and immunoblot analyses. Northern blot analysis showed that the
      gamma and delta subunits of CaM kinase II are mainly expressed in PC12 cells.
      Treatment of the cells with ionomycin activated CaM kinase II alpha through
      autophosphorylation and generation of the Ca2+/calmodulin-dependent form. It is
      interesting that the neurite outgrowth induced by dibutyryl cyclic AMP was
      inhibited in these cell lines in accordance with the activities of overexpressed
      CaM kinase II alpha. The activity of cyclic AMP-dependent protein kinase showed
      similar levels among these cell lines. These results suggest that CaM kinase II
      is involved in the modulation of the neurite outgrowth induced by activation of
      the cyclic AMP system.

PMID- 8522990
TI  - Cyclooxygenase-2 induction in cerebral cortex: an intracellular response to
      synaptic excitation.
AB  - We have characterised the induction of the mitogen-inducible form of
      cyclooxygenase, COX-2, in the rat cerebral cortex in response to excitotoxin
      injection into the nucleus basalis. This model is associated with intense
      stimulation of the ascending pathway to the cerebral cortex, seizure activity,
      and subsequent ipsilateral cortical induction of various immediate early genes
      (IEGs), including c-fos, c-jun, and zif268, and ornithine decarboxylase enzyme
      activity and mRNA, all of which processes are sensitive to treatment with the N
      methyl-D-aspartate (NMDA) receptor antagonist MK-801. In this study we show that
      excitotoxin injection also causes a marked induction of COX-2 mRNA in ipsilateral
      cortex detectable at 1 h and peaking at 4 h, where COX-2 mRNA levels were 19
      times those in unoperated animals. Levels of COX-2 mRNA remained significantly
      elevated at 24 h. The early induction of COX-2 at 1 h was also seen in sham
      operated animals, but at 4 h the COX-2 mRNA level was significantly increased
      (4.4-fold) in animals injected with excitotoxin compared with sham-operated
      animals. The induction at this time point (4 h) was explored pharmacologically
      and found to be significantly attenuated by treatment with MK-801 (1.5 mg/kg),
      lamotrigine (10 mg/kg), which prevents presynaptic glutamate release by blocking
      voltage-sensitive Na+ channels, and the glucocorticoid dexamethasone (3 mg/kg),
      which has an indirect inhibitory effect on phospholipase A2 and COX
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522991
TI  - Stimulation of cloned human serotonin 5-HT1D beta receptor sites in stably
      transfected C6 glial cells promotes cell growth.
AB  - The involvement of serotonin 5-HT1D beta receptor sites was investigated in the
      growth of rat C6 glial cells permanently transfected with a gene encoding a human
      5-HT1D beta receptor. The 5-HT receptor identity of control and transfected C6
      glial/5-HT1D beta cells was determined by reverse transcription-polymerase chain
      reaction using primers specific for rat 5-HT1A, rat 5-HT1B, rat 5-HT1D alpha,
      human 5-HT1D beta, and rat 5-HT2A receptor genes. Constitutive mRNA for 5-HT2A
      receptors was present in control and transfected C6 glial/5-HT1D beta cells,
      whereas mRNA for 5-HT1D beta receptor sites was only present in the transfected
      C6 glial/5-HT1D beta cell line. 5-HT inhibited forskolin-stimulated cyclic AMP
      formation and promoted cell growth, in contrast to the absence of any measurable
      effect in pcDNA3 plasmid-transfected and nontransfected C6 glial cells. The 5-HT
      effects could be mimicked by sumatriptan (EC50 = 44-76 nM) and were totally and
      partially blocked by methiothepin (IC50 = 9 nM) and GR 127,935 (2'-methyl-4'-(5
      methyl[1,2,4]oxadiazol-3-yl)-biphenyl-4-carbox yli c acid [4-methoxy-3-(4
      methylpiperazin-1-yl)phenyl]amide; IC50 = 97 pM), respectively. No effect on cell
      growth was measured with the 5-HT2 receptor agonist DOI [1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane; 10 microM], suggesting that 5-HT2A receptors are not
      involved in the 5-HT-stimulated C6 glial/5-HT1D beta cell growth. Dibutyryl
      cyclic AMP (0.3 mM)-treated cultures did not show sumatriptan-promoted cell
      growth, indicating an inhibitory role for cyclic AMP in the cell growth mediated
      by 5-HT1D beta receptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8522992
TI  - Glial cell line-derived neurotrophic factor exerts neurotrophic effects on
      dopaminergic neurons in vitro and promotes their survival and regrowth after
      damage by 1-methyl-4-phenylpyridinium.
AB  - The effect of glial cell line-derived neurotrophic factor (GDNF) on the growth of
      mesencephalic dopaminergic neurons and on their survival following exposure to
      the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) was examined in vitro. In
      cultures developing under normal conditions, GDNF at 1 ng/ml optimally improved
      the survival and stimulated the growth of dopaminergic neurons without affecting
      glial growth. In cultures treated with MPP+, GDNF could not prevent toxicity to
      dopaminergic neurons. The uptake of [3H]dopamine and the number of tyrosine
      hydroxylase-positive neurons were similarly reduced by MPP+ in the presence or
      absence of GDNF. However, after removal of MPP+, GDNF protected dopaminergic
      neurons from the continuous cell death and stimulated the regrowth of
      dopaminergic fibers damaged by MPP+. We conclude that GDNF supports the growth of
      normally developing dopaminergic neurons and stimulates their survival and
      recovery after damage. These findings suggest that GDNF could be useful in the
      development of therapeutic approaches to Parkinson's disease, which is
      characterized by dopaminergic cell loss.

PMID- 8522993
TI  - Cyclic AMP-independent inhibition of voltage-sensitive calcium channels by
      forskolin in PC12 cells.
AB  - Forskolin has been used to stimulate adenylyl cyclase. However, we found that
      forskolin inhibited voltage-sensitive Ca2+ channels (VSCCs) in a cyclic AMP
      (cAMP)-independent manner in PC12 cells. Ca2+ influx induced by membrane
      depolarization with 70 mM K+ was inhibited when cells were preincubated with 10
      microM forskolin. Almost maximum inhibitory effect on Ca2+ influx without any
      significant increase in cellular cAMP level was observed in PC12 cells exposed to
      forskolin for 1 min. In addition, the forskolin effect on Ca2+ influx was not
      affected by the presence of 2',5'-dideoxyadenosine, an inhibitor of adenylyl
      cyclase that reduces dramatically forskolin-induced cAMP production. 1,9
      Dideoxyforskolin, an inactive analogue of forskolin, also inhibited approximately
      80% of Ca2+ influx induced by 70 mM K+ without any increase in cAMP. The data
      suggest that forskolin and its analogue inhibit VSCCs in PC12 cells and that the
      inhibition is independent of cAMP generation.

PMID- 8522994
TI  - Comparison of the effects of retinoic acid and nerve growth factor on PC12 cell
      proliferation, differentiation, and gene expression.
AB  - Retinoic acid (RA) produced a dose-dependent inhibition of PC12 cell growth and
      the appearance of cell clusters without neurite extension. RA-induced cell
      clumping was similar to that caused by dexamethasone (Dx). Nerve growth factor
      (NGF) induced neurite extension, and the combination of RA plus NGF produced a
      maximal decrease in cell proliferation with a mixed morphology in which part of
      the cell population had neurites and part formed clumps. Transcriptional effects
      of RA were demonstrated by the increase in the activity of reporter constructs
      that contain an RA response element. RA also regulated expression of endogenous
      genes in PC12 cells. The retinoid produced a two- to threefold increase in level
      of p75LNGFR mRNA (the low-affinity NGF receptor), without altering expression of
      the trk protoon-cogene (the high-affinity NGF receptor carrying tyrosine kinase
      activity). RA also caused a transient increase in level of tyrosine hydroxylase
      (TH) mRNA (twofold after 16 h), which returned to basal levels and then decreased
      relative to basal levels at 48 h. The effect of NGF on the expression of these
      genes was identical to that produced by RA. However, incubation with Dx did not
      induce p75LNGFR mRNA and produced a strong and sustained increase of TH mRNA
      level (three- to fivefold after 48 h). These results show that, despite the
      common morphological changes produced by RA and glucocorticoids in PC12 cells,
      the biochemical changes caused by RA are similar to those produced by NGF.
      Therefore, RA could initiate a biochemical program of neuronal differentiation in
      PC12 cells, although a fully differentiated phenotype with neurite extension is
      not obtained.

PMID- 8522995
TI  - Glutamate induces a calcineurin-mediated dephosphorylation of Na+,K(+)-ATPase
      that results in its activation in cerebellar neurons in culture.
AB  - In primary cultures of cerebellar neurons glutamate neurotoxicity is mainly
      mediated by activation of the NMDA receptor, which allows the entry of Ca2+ and
      Na+ into the neuron. To maintain Na+ homeostasis, the excess Na+ entering through
      the ion channel should be removed by Na+,K(+)-ATPase. It is shown that incubation
      of primary cultured cerebellar neurons with glutamate resulted in activation of
      the Na+,K(+)-ATPase. The effect was rapid, peaking between 5 and 15 min (85%
      activation), and was maintained for at least 2 h. Glutamate-induced activation of
      Na+,K(+)-ATPase was dose dependent: It was appreciable (37%) at 0.1 microM and
      peaked (85%) at 100 microM. The increase in Na+,K(+)-ATPase activity by glutamate
      was prevented by MK-801, indicating that it is mediated by activation of the NMDA
      receptor. Activation of the ATPase was reversed by phorbol 12-myristate 13
      acetate, an activator of protein kinase C, indicating that activation of Na+,K(+)
      ATPase is due to decreased phosphorylation by protein kinase C. W-7 or
      cyclosporin, both inhibitors of calcineurin, prevented the activation of Na+,K(+)
      ATPase by glutamate. These results suggest that activation of NMDA receptors
      leads to activation of calcineurin, which dephosphorylates an amino acid residue
      of the Na+,K(+)-ATPase that was previously phosphorylated by protein kinase C.
      This dephosphorylation leads to activation of Na+,K(+)-ATPase.

PMID- 8522996
TI  - Increasing prevalence of femoral lysis in cementless total hip arthroplasty.
AB  - A follow-up study was made of 94 primary total hip arthroplasties in 86 patients
      with a Harris-Galante (Zimmer, Warsaw, IN) porous-coated femoral component
      implant to determine the change in prevalence of femoral lysis and its clinical
      significance. At a mean follow-up period of 53 months (range, 16-86 months),
      femoral lysis was present in 31% of the femurs. In the first report of this
      condition, the incidence was 3%. The mean patient age was 54 years (range, 30-69
      years). The most common diagnosis was osteoarthritis (62 hips). Of the 29 hips
      with femoral lysis, 11 were graded as extensive. Of the 14 hips in which the
      femoral component was defined as loose, 12 had femoral osteolysis; however, the
      mean Harris hip score among those with lysis was not reduced in those with
      femoral osteolysis (88 compared with 90 the entire group). Pelvic osteolysis, in
      contrast, was present in only one hip, around a screw. In this series, femoral
      lysis was a major complication, whether the femoral component was stable or not,
      and the prevalence of lysis increased sharply over time.

PMID- 8522997
TI  - Heterotopic ossification following primary total knee arthroplasty.
AB  - Ninety-eight consecutive primary total knee arthroplasties (TKAs) in 70 patients
      were retrospectively evaluated for heterotopic ossification (HO). A radiographic
      classification was devised based on the extent and location of the ectopic bone.
      Twenty-five knees (26%) in 19 patients developed HO. Eight of 11 patients (73%)
      with preexisting heterotopic bone at other sites developed HO in the index knee.
      Multivariate analysis demonstrated that advanced HO was associated with
      restricted knee motion. Eight knees with advanced HO had a mean 14 degrees
      decrease in postoperative, as compared with preoperative, knee flexion (P < .05).
      For all patients with HO, mean lumbar spine bone mineral density (BMD) was
      significantly elevated compared with a matched control group not developing HO (P
      < .05). Heterotopic ossification following primary TKA correlates with a
      limitation of postoperative knee flexion and is predicted by increased lumbar
      BMD. Preoperative measurement of spinal BMD may identify those patients at risk
      for HO and allow for the institution of preoperative prophylaxis and modification
      of postoperative rehabilitation to optimize functional outcome following TKA.

PMID- 8522998
TI  - Efficacy of intraoperative cultures obtained during revision total hip
      arthroplasty.
AB  - The purpose of this study was to determine the incidence of positive
      intraoperative cultures, correlate the findings of the permanent histopathology
      with the results of culture, and determine the natural history and predictive
      value of the positive intraoperative culture in a consecutive series of 138
      revision total hip arthroplasties. The incidence of positive cultures was 30% (42
      hips). Of these 42 hips, only 1 ultimately developed sepsis, requiring a second
      surgical procedure. After a mean follow-up period of 48 months, the remaining 41
      culture-positive hips show no evidence of sepsis and are considered clinical
      successes. The histologic appearance of the infected case was characterized by
      polymorphonuclear leukocyte infiltration suggestive of acute inflammation. The
      remaining hips demonstrated findings of chronic inflammation consistent with a
      diagnosis of aseptic loosening. With the development of sepsis as an endpoint,
      the positive predictive value of a positive intraoperative culture is 2.4%. The
      results demonstrate that intraoperative cultures are an unreliable predictor of
      sepsis and that permanent histologic sectioning is a more useful tool in
      determining sepsis at the time of revision surgery.

PMID- 8522999
TI  - Posterolateral arthritis of the knee.
AB  - Arthritis in the posterolateral quadrant of the knee presents typical
      arthroscopic findings. With careful history, physical examination, and
      appropriate radiographs, it can be an office diagnosis. The history, physical
      findings, and arthroscopic findings in 15 patients with this problem were
      reviewed. Symptoms of posterolateral pain, give-way, and pain with stairclimbing
      were common. The only frequent physical findings were those of pain with the
      lateral meniscal entrapment test or pain with the pivot shift test. No
      ligamentous instability was noted. Weight-bearing radiographs demonstrated severe
      lateral chondral loss in flexion, but not in extension. Arthroscopic findings
      were typical. Previous injury to the posterior portion of the lateral meniscus
      was common. This seems to be a traumatic, rather than a degenerative, process.
      Three patients had varus-producing osteotomy of the distal femur. This was not
      effective in relieving their symptoms.

PMID- 8523000
TI  - Postoperative blood salvage in total knee arthroplasty using the Solcotrans
      autotransfusion system.
AB  - One hundred forty-four patients who underwent primary total knee arthroplasty
      were examined in a prospective controlled study to determine the efficacy and
      safety of a postoperative wound drainage autotransfusion system (Solcotrans,
      Smith & Nephew Richards, Memphis, TN). The patients were divided into two groups:
      control group 1 comprised 88 (61%) patients who either received a Hemovac
      disposable drainage system (63 patients) or the Solcotrans system and had
      inadequate drainage for autotransfusion (25 patients). Experimental group 2
      comprised 56 (39%) patients who received a Solcotrans drainage system and were
      autotransfused. The Solcotrans proved itself safe. No sepsis, transfusion
      reactions, or coagulopathies were associated with autotransfusion, which averaged
      524 mL. There were no significant differences between groups 1 and 2 when
      comparing preoperative and postoperative hemoglobins and hematocrits. The
      Solcotrans system did not lower homologous blood requirements. Only 1.6% (2
      patients) of all patients who autodonated at least 2 units of autologous blood
      (122 patients) were in need of a homologous blood transfusion in the
      postoperative period. Thus, although safe, the Solcotrans system was not proven
      effective in the management of primary total knee arthroplasty patients.

PMID- 8523001
TI  - Hybrid fixation modular tibial prosthesis. Early clinical and radiographic
      results and retrieval analysis.
AB  - A prosthetic tibial component has been designed with features for fixation to
      bone using a combination of acrylic cement and ingrowth interfaces. This hybrid
      concept affords the component the immediate stability of cement fixation and the
      potential long-term stability of biologic fixation. The ingrowth interfaces
      (coupled with the central stem) are intended to shield the cement interface
      beneath the tibial tray from the tensile liftoff forces that result from
      eccentric loading, while avoiding the fretting and osteolysis associated with
      screw fixation. A disassembly capability allows the tray to be removed from the
      stemmed anchorage assembly, facilitating component extraction and limiting bone
      loss. A clinical and radiographic review of 50 consecutive primary total knee
      arthroplasties with a mean follow-up period of 35 months revealed stable
      interfaces with no progressive radiolucencies and minimal remodeling changes. The
      mean Knee Society knee score was 92.2. At final follow-up evaluation, 88.6% of
      patients noted no or mild (occasional) pain. Retrieval of three prosthetic knees
      with chronic sepsis showed extensive ingrowth into the porous interfaces and an
      osteointegrated bony sleave around the smooth central stem.

PMID- 8523002
TI  - Total knee arthroplasty in human immunodeficiency virus-infected hemophiliacs.
AB  - Twenty-six knee arthroplasties were performed in 15 patients with hemophilia A
      and human immunodeficiency virus infection from 1984 to 1991. Patient age range
      was 27 to 48 years. After an average follow-up period of 6.4 years (range, 1-9
      years) all patients were alive and none of the implants had become infected. T4
      lymphocyte counts showed some deterioration, which was not clinically
      significant. All of the patients were improved following surgery. Nineteen
      implants were rated excellent, four good, and three fair. Infection with human
      immunodeficiency virus did not adversely affect the clinical outcome of knee
      arthroplasty at follow-up periods up to 9 years.

PMID- 8523003
TI  - Effect of varying surface patterns on antibiotic elution from antibiotic-loaded
      bone cement.
AB  - In an effort to improve the antibiotic elution characteristics of the prosthesis
      of antibiotic-loaded acrylic cement, an in vitro study was conducted. Tobramycin
      loaded bone cement blocks of three different surface patterns with different
      surface area-to-volume ratios were used. The elution of tobramycin over a 2-month
      period was investigated. There was a gradual decline in the tobramycin elution
      rate over time. The surface pattern with the increased surface area-to-volume
      ratio showed a significant increase in the tobramycin elution rate over the first
      week of the study. The surface pattern with ridges but no change in the surface
      area-to-volume ratio did not result in a statistically significant increase in
      the tobramycin elution rate.

PMID- 8523004
TI  - Prospective 5- to 6-year follow-up study of a cementless acetabular cup.
AB  - Twenty-seven patients in whom the Ti-Bac acetabular cup (Zimmer, Warsaw, IN) was
      placed were examined 5 to 6 years after surgery. The cup was inserted line to
      line, after reaming without further fixation. In all operations, a cemented
      Muller straight-stem Protazul femur stem (Zimmer) was used. The patients had good
      pain relief and improved mobility after the operation. Radiographically, only one
      hip showed radiolucency in the bone-metal interface after 5 to 6 years. One
      patient was reoperated 3 days after surgery because of dislocation of the
      acetabular cup. Apart from this, there were no signs of aseptic loosening of any
      of these uncemented cups.

PMID- 8523005
TI  - Distal stem design and the torsional stability of cementless femoral stems.
AB  - In cementless hip arthroplasty, the fit between the implant and the endosteal
      cavity is a critical determinant of implant stability. Although cementless
      implants may be stabilized through proximal fit within the metaphysis, many
      surgeons rely on diaphyseal fixation to provide the necessary resistance to
      rotational forces, especially in revision hip arthroplasty. The cross-sectional
      design of the femoral stem at the level of the femoral isthmus was investigated
      with respect to its effect on the rotational stability of the bone-stem
      interface. Four cross-sectional designs--a fluted stem, a finned stem, a porous
      coated stem, and a slotted fluted stem--were implanted in 12 cadaveric femurs and
      loaded in torsion. A knurled stem, cemented into each specimen at the conclusion
      of testing, acted as a control stem. The torque required to cause 100 microns of
      displacement at the bone stem-interface ranged from 13.7 +/- 0.8 N-m with the
      porous-coated design to 30.1 +/- 3.7 N-m with the fluted design (P < .0001).
      Intermediate values of 19.5 +/- 1.4 and 19.9 +/- 2.3 N-m were observed with the
      finned and slotted fluted designs, respectively. In all of the cemented control
      stems, failure occurred at the bone-cement interface at an average torque of 34.0
      +/- 3.0 N-m. Statistical analysis demonstrated that the porous-coated, finned,
      and slotted fluted designs were all significantly weaker in torsion than the
      cemented control stem; however, there was no significant difference between the
      torsional resistance of the solid fluted (unslotted) and cemented stems.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8523006
TI  - Use of antibiotic-impregnated cement during hip and knee arthroplasty in the
      United States.
AB  - A survey of practicing orthopaedists regarding their use of antibiotic(s) in bone
      cement (ABC) was carried out. The initial sampling of 2,139 orthopaedists spanned
      the continental United States. Responses that passed fail-edit criteria were
      obtained from 1,015 physicians. Clinical practice patterns are highly variable.
      Adult reconstructive orthopaedic practitioners' belief in antibiotic(s) in bone
      cement for the treatment of patients with previous sepsis is favorable. This
      opinion can be supported at the guideline level. Guidelines suggesting that
      liquid antibiotics should not be used as additions to polymethyl methacrylate are
      also supportable. The need for careful scientific inquiry and cost-effectiveness
      evaluation of the benefits and risks relating to the use of antibiotic additions
      to polymethyl methacrylate cement in joint arthroplasty exists. On the basis of
      such inquiry, educational dissemination to reduce practice variation would be
      indicated.

PMID- 8523007
TI  - Thermal expansion modular femoral head extractor for revision total hip
      arthroplasty.
AB  - Removal of a prosthetic modular femoral head is sometimes desirable during
      revision hip arthroplasty. A femoral head extractor was designed to heat and
      expand the prosthetic femoral head, apply a gentle distraction load, and remove
      the femoral head without injury to the femoral neck, taper, or bone-prosthesis
      interface. The device was used clinically in six hip revision cases. In five hips
      with cobalt-chrome heads and titanium alloy tapers, femoral heads were removed
      successfully; femoral fixation was maintained and femoral components were not
      visibly damaged. In the sixth case, the female portion of the taper junction was
      contained in a long femoral head sleeve. Heating the ball did not adequately
      expand the sleeve to allow easy ball removal.

PMID- 8523008
TI  - Tibiofemoral contact stress and stress distribution evaluation of total knee
      arthroplasties.
AB  - The Fuji film (Itochu, Los Angeles, CA) area analysis technique demonstrates that
      a more accurate assessment of tibiofemoral contact stresses is possible when the
      film is used at 37 degrees C and at the upper end of its sensitivity range (in
      this case, a 2,000-N load). An AMK with a regular and Hylamer-M insert (DePuy,
      Warsaw, IN), an MG II (Zimmer, Warsaw, IN), an Omnifit (Osteonics, Allendale,
      NJ), an Ortholoc III (Dow Corning Wright, Midland, MI), a PCA II (Howmedica,
      Rutherford, NJ), and a PFC (Johnson & Johnson Orthopaedics, Raynham, MA) had
      average contact stresses that varied only 12% at 60 degrees flexion. At 0
      degrees, 15 degrees and 60 degrees flexion, stresses ranged from 13 to 25 MPa.
      Contact area distribution ratios, which were smaller at 37 degrees C than at 24
      degrees C, provide a quantitative means of grouping implants according to the
      shape of the tibiofemoral contact area. The Omnifit, MG II, PCA II, and PFC had
      small ratios (symmetric areas). The AMK and Ortholoc III had large ratios
      (asymmetric contact areas). If the impression is reflective of wear, it would be
      expected to be focal in knees with small ratios and contact areas, and uniform in
      knees with large ratios and contact areas, whereas large ratios and small areas
      would imply a linear wear pattern. Calibrated electrical resistance contact
      stress measurements indicated that the Fuji film measurements underestimated the
      magnitude of contact stresses. They also provided a means of quantifying the rate
      of area increase during initial loading of the knees, with the highest area
      increase noted for the knee with the roughest insert (Ortholoc III) and the
      lowest area increase for the knee with the smoothest insert (PCA II).

PMID- 8523009
TI  - Factors influencing pressurization of the femoral canal during cemented total hip
      arthroplasty.
AB  - Successful cement pressurization with total hip arthroplasty depends on the
      capacity of the cement gun and its ability to pressurize the canal and the
      integrity of the intramedullary plug and the proximal seal used to contain the
      cement bolus during pressurization. In the laboratory, the authors measured the
      volume of cement delivered by two cement guns (from Zimmer, Warsaw, IN, and
      Howmedica, Rutherford, NJ) in comparison with typical values for the volume of
      the medullary canal following standard surgical preparation. The two cement guns
      studied delivered 93 and 138 mL cement, respectively. In comparison, the volume
      of the intramedullary canal ranged from 35 to 70 mL using a standard femoral
      prosthesis (Precision Hip System, Howmedica). Peak pressures developed during
      cement injection using the cement guns were 73.6 +/- 27.1 psi for the Zimmer
      system and 47.3 +/- 16.9 psi for the Howmedica system. Both devices were able to
      sustain a minimum pressure of at least 6.5 psi through cementing when used in
      conjunction with a flexible pressurizing seal. The mechanical performance of five
      designs of intramedullary plugs was assessed by monitoring plug displacement
      during cement pressurization in reamed cortical specimens. The performance of
      each device was judged by its ability to withstand cement pressures of 50 psi
      without displacement within the medullary canal. On the basis of this test, the
      probability that these plugs would exceed this criterion when used with the femur
      was estimated to range from 24 to 94%. Few of the commercially available plugs
      were able to withstand cement pressures routinely generated using standard cement
      delivery systems.

PMID- 8523011
TI  - Determination of accuracy of preoperative templating of noncemented femoral
      prostheses.
AB  - The purpose of this study was to determine the accuracy of preoperative
      templating of primary, noncemented femoral components. A retrospective review of
      charts and radiographs was performed on 74 hips in 64 patients who had undergone
      either noncemented total hip arthroplasty (THA) or placement of an endoprosthesis
      (including bipolar). Preoperative radiographs were templated by a total joint
      arthroplasty attending surgeon, a senior orthopaedic resident, and a junior
      resident. The templated size corresponded to the actual femoral implant used in
      approximately 50% of cases. When femoral prostheses within one size above or
      below the templated size were included, the accuracy of preoperative templating
      rose to 88-95%. When implants within two sizes of the templated size were
      included, the accuracy approached 100%. Factors associated with discrepancies in
      the size of femoral stem used included placement of an undersized implant,
      presence of metal hardware that obscured the ability to template accurately,
      proximal bone deformity, sclerotic bone, acute femoral neck fracture, and
      inadequate preoperative radiographs. The accuracy of templating increased
      gradually with the level of training. The most experienced investigator was able
      to template within one size of the actual implant used in 95% of cases, compared
      with 88% and 82% for the less experienced investigators. Acute femoral neck
      fractures and proximal bone deformity were associated with the largest
      discrepancies in templated sizes.

PMID- 8523010
TI  - Cellular mediators secreted by interfacial membranes obtained at revision total
      hip arthroplasty.
AB  - The interfacial membrane between implant and host-bone in aseptically loose total
      hip arthroplasties has a potential role in the etiology of local bone resorption
      and loosening of the prosthetic component. Inflammatory/potential "bone
      resorbing" agents (cytokines/mediators) released by the cells of the interfacial
      membranes of loosened uncemented and cemented total hip arthroplasties were
      measured. Synovial tissues from patients with acute femoral neck fractures,
      patients with osteoarthritis, and cadavers without joint disorders were used as
      control subjects. Control synovial tissue from osteoarthritic patients secreted
      the highest levels of prostaglandin E2, interleukin-8, and tumor necrosis factor
      alpha. Interleukin-1 alpha was the only cytokine whose levels were elevated as
      much as 4-fold around uncemented implants compared with cemented implants, and up
      to 16-fold compared with control synovial tissue. An apparent inverse relation
      between interleukin-1 alpha and interleukin-6 interfacial membranes of total hip
      arthroplasties compared with control synovial tissues suggests a complex cellular
      mechanism through a cytokine/prostaglandin cascade; this may regulate the
      observed bone resorption in aseptic loosening.

PMID- 8523012
TI  - Mechanical influences on tissue differentiation at bone-cement interfaces.
AB  - Retrieval studies have shown that tissue at the bone-cement or bone-implant
      interface can develop into fibrous tissue, fibrocartilage, and bone, and that
      tissue differentiation appears to be mechanically influenced. A prior histologic
      analysis of retrieved interface tissues supporting cemented Marmor unicondylar
      knee components found that beneath the central portion of these implants, a
      thick, mature layer of fibrocartilage consistently developed, whereas fibrous
      tissue formed beneath the prosthesis periphery and adjacent to the bone beneath
      the tibial spine. Finite-element analysis was used to model the interface tissue
      supporting a cemented Marmor tibial component and interpreted patterns of stress
      and strain generated in the interface according to a mechanically based tissue
      differentiation theory. Distortional strain and hydrostatic stress, mechanical
      stimuli that are hypothesized to be associated with fibrous matrix and
      cartilaginous matrix production, respectively, were found to correlate well with
      the previous histologic findings. Given the biologic environments in which the
      retrieved interface tissues developed, frequently applied hydrostatic stress of
      approximately 0.7 MPa may be sufficient to stimulate cartilaginous extracellular
      matrix production in the interface tissue, and frequently applied distortional
      strain of 10% may be sufficient to stimulate fibrous extracellular matrix
      production.

PMID- 8523013
TI  - Changes in circulatory indices of thrombosis and fibrinolysis during total knee
      arthroplasty performed under tourniquet.
AB  - Deep vein thrombosis may begin during surgery with the tourniquet inflated.
      Arterial levels of fibrinopeptide A, thrombin-antithrombin complexes, D-dimer,
      tissue plasminogen activator (t-PA) activity, and t-PA antigen were measured
      before surgery, during surgery with the tourniquet inflated, and following
      deflation of the tourniquet in 12 patients undergoing total knee arthroplasty.
      Minimal increases in fibrinopeptide A, thrombin-antithrombin complexes, and D
      dimer were noted during surgery with the tourniquet inflated, but significant
      increases occurred immediately following deflation of the tourniquet. In 10
      patients, intravenous heparin administration significantly suppressed the rise in
      fibrinopeptide A, but did not significantly alter the increases in either
      thrombin-antithrombin complexes, D-dimer, t-PA antigen, or t-PA activity. This
      study provides further evidence that deep vein thrombosis begins during surgery.

PMID- 8523014
TI  - Total hip arthroplasty for arthrodesed hips. 5- to 13-year results.
AB  - The functional outcome of total hip arthroplasty for arthrodesed hips was
      evaluated. During the years 1979 to 1988, 55 arthrodesed hips were converted to
      total hip arthroplasties. Thirty-seven women and nine men were followed for a
      minimum of 5 years. Thirteen of the patients were very much satisfied with the
      operation, 19 were much satisfied, 7 were satisfied, 3 were less satisfied, and 4
      were unsatisfied. The Harris hip score was improved from 51-83 at the time of
      operation to 53-93 at the follow-up examination. Before conversion, none of the
      patients used crutches. At the follow-up examination, 10 patients used two
      crutches, 24 used one crutch, and 12 did not need support. Muscle strength of the
      abductors ranged from 1 to 4. In 26 patients with major low back pain before
      conversion, the pain score improved from 3-10 at the time of operation to 0-8 at
      the follow-up examination. This study shows that with conversion of an
      arthrodesed hip to arthroplasty, most patients need support for walking; however,
      they are generally grateful for their new mobility, maneuverability, and improved
      ability to sit comfortably.

PMID- 8523015
TI  - Prospective randomized evaluation of blood salvage techniques for primary total
      hip arthroplasty.
AB  - A controlled, randomized, prospective study was performed evaluating the need for
      perioperative blood salvage for primary total hip arthroplasty patients who had
      donated autologous blood before surgery. One hundred fifty-three patients able to
      donate at least 2 units of autologous blood were divided into four groups. In
      group 1 (35 patients), intraoperative and postoperative Cell-Saver (Haemonetics,
      Braintree, MA) was employed. In group 2 (40 patients), a postoperative Solcotrans
      (Smith & Nephew Richards, Memphis, TN) reinfusion protocol was followed. In group
      3 (40 patients), a closed-suction Hemovac drain (Zimmer, Warsaw, IN) was placed.
      In group 4, (38 patients), no drain was used. Decisions for transfusion were
      based on clinical and laboratory parameters and made in conjunction with medical
      consultation. All autologous blood was routinely reinfused. There was no
      statistically significant difference in transfusion requirements or wound
      complications among the four groups. Hemoglobin and hematocrit changes between
      groups also were not statistically significant, but a power test suggested
      insufficient patient numbers for absolute reliability of this observation. Only
      five patients (3.3%) in this study received homologous blood. Four of these
      patients were in the Solcotrans group and one was in the Cell-Saver group. Two
      reoperations were performed: one for hematoma (Solcotrans group) and one for a
      sewn-in drain. It is concluded that expensive perioperative blood salvage
      techniques are usually not needed in patients who have a primary total hip
      arthroplasty without cement and who have donated 2 units of blood before
      operation.

PMID- 8523016
TI  - Lateral patellar burnishing in total knee arthroplasty following medialization of
      the patellar button.
AB  - This case report describes a total knee revision necessitated by painful contact
      between the exposed lateral facet of the patella and the femoral component. Pain
      was resolved following repositioning and enlarging the patellar component. The
      clinical significance of this report is that the contemporary practice of
      medializing the patellar component to improve patellar tracking should be
      performed in moderation to avoid overexposure of the lateral patella. In the
      setting of persistent anterior knee pain following total knee arthroplasty, the
      etiology of the pain may be identified as contact between the patellar and
      femoral component on the sunrise radiograph.

PMID- 8523017
TI  - Popliteus tendon dysfunction following total knee arthroplasty.
AB  - The popliteus tendon can be a potential source of internal derangement after
      total knee arthroplasty. It can subluxate anteriorly and posteriorly over a
      retained lateral femoral condylar osteophyte or over the overhanging edge of the
      metallic posterior femoral condyle. Surgical release of the tendon from its
      femoral insertion relieves the problem.

PMID- 8523018
TI  - Anterior iliopsoas impingement after total hip arthroplasty.
AB  - Pain after total hip arthroplasty (THA) can be caused by a multitude of
      conditions, including infection, aseptic loosening, heterotopic ossification, and
      referred pain. It is also recognized that soft tissue inflammation about the hip,
      such as trochanteric bursitis, can lead to hip pain after THA. Two cases of
      persistent iliopsoas tendinitis following THA are reported, which are believed to
      be caused by psoas tendon impingement against a malpositioned, uncemented, metal
      backed acetabular component. The authors are unaware of previous reports of this
      problem, and suggest that the problem be considered in the differential diagnosis
      of groin pain following THA.

PMID- 8523019
TI  - Postoperative fracture of the host femur in allograft-prosthetic reconstruction
      of the hip.
AB  - Massive allograft-prosthetic reconstruction of the proximal femur during revision
      total hip arthroplasty has yielded successful early results in cases of severe
      bone deficiency; however, recommendations differ as to the type of prosthesis to
      be employed and the method of achieving rigid fixation of the allograft. In
      regard to the bony configuration at the allograft-host junction, a step-cut
      osteotomy, a transverse osteotomy, and an oblique osteotomy have all been
      reported. A case is presented in which fracture of the host femur occurred distal
      to a step-cut osteotomy in osteoporotic bone.

PMID- 8523020
TI  - Streptococcus bovis-infected total hip arthroplasty.
AB  - The case of a 51-year-old man who underwent a total hip arthroplasty following
      failed AO screw fixation of a subcapital femoral neck fracture is reported.
      Infection of the prosthesis with Streptococcus bovis type 1 followed a febrile
      illness. Further investigation revealed an occult premalignant polyp in the
      proximal colon. Colonic neoplasia and S. bovis bacteremia are associated with
      endocarditis; however, S. bovis is a rare pathogen infecting joint prostheses and
      should raise the possibility of a gastrointestinal lesion.

PMID- 8523021
TI  - Reversible osteolysis.
AB  - This is a case report of a 44-year-old patient in whom osteolytic changes that
      developed around the distal end of the femoral prosthesis appeared to reverse
      with the use of antiinflammatory medication and pulsed electromagnetic field
      stimulation. Most reported cases of osteolysis have been described as showing
      progressive change at a variable rate. There has not been any previously
      documented case in which there has been reversal of osteolytic change.

PMID- 8523022
TI  - Total knee arthroplasty.

PMID- 8523023
TI  - Triad cemented total hip prosthesis.

PMID- 8523024
TI  - Brain failure in world leaders: should neurologists speak out?

PMID- 8523025
TI  - Affinity of antigen-specific IgG distinguishes multiple sclerosis from
      encephalitis.
AB  - The characteristics of antigen-specific IgG in patients with multiple sclerosis
      and patients with encephalitis have been compared. Both groups of patients showed
      antigen-specific oligoclonal bands locally synthesised in the CSF. When the
      affinity distribution of the antigen-specific IgG was measured there was a marked
      difference between the two groups. Encephalitis patients had high affinity
      antibody against the causative antigen. This was consistent with the antibody
      undergoing affinity maturation as a result of the immune system fighting a
      primary infection. Multiple sclerosis patients lacked high affinity response.
      This lack of high affinity antibody was also seen in those encephalitis patients
      when antigens other than the causative antigen were studied.

PMID- 8523027
TI  - REM sleep without atonia at early stage of sporadic olivopontocerebellar atrophy.
AB  - In order to investigate whether REM sleep without atonia (RWA) is detected even
      at early stage of sporadic olivopontocerebellar atrophy (OPCA), all-night
      polysomnography with video monitoring was performed on 5 patients presenting with
      no nocturnal behavioral complaints. RWA associated with sleep talk and/or minor
      movements in the head, neck, face and extremities was documented in all cases.
      Preserved proper NREM/REM cycle and relatively normal sleep architecture suggest
      the abnormality is confined to REM sleep. Dysfunction of the mechanisms
      underlying muscle atonia in REM sleep, especially functional or anatomical
      interruption of ponto-medullary pathways mediating REM sleep atonia, seems to
      cause RWA in these patients. RWA may be a clinically important finding as a sign
      of brainstem dysfunction at early stage of neurodegenerative diseases.

PMID- 8523026
TI  - Alteration of blood-brain barrier in human brain tumors: comparison of
      [18F]fluorodeoxyglucose, [11C]methionine and rubidium-82 using PET.
AB  - The influence of the blood-brain barrier (BBB) on tracer uptake was investigated
      in 21 patients with gliomas and meningiomas using PET, [18F]fluorodeoxyglucose
      (FDG), [18C]methionine (MET) and the K+ analog rubidium-82 (RUB) whose uptake
      into brain is largely prevented if the BBB is intact. Tracer uptake was
      quantitated by (1) multiple time graphical plotting providing tracer distribution
      volume (VD), unidirectional tracer uptake (Ki), and (2) normalized uptake (NU)
      which is a measure of net tissue radioactivity related to administered activity
      and body weight. VD, Ki and NU of MET were higher in meningiomas compared to
      gliomas and were significantly correlated with NU RUB (Spearman rank: p < 0.005
      (VD), p < 0.05 (Ki), p < 0.001 (NU)). NU MET correlated with VD (p < 0.001) and
      Ki (p < 0.005) of MET. For FDG, tumor VD was in the range of contralateral
      cortex. Ki and NU values of FDG were highest in glioblastomas. NU of FDG
      correlated significantly with Ki of FDG (p < 0.005) but not with VD. The results
      suggest, that alteration of MET uptake in tumors is governed by changes of tracer
      influx across the BBB, whereas FDG uptake is related to tracer metabolism. This
      makes FDG the appropriate tracer particularly for the differential diagnosis of
      contrast enhancing lesions in operated and irradiated patients.

PMID- 8523028
TI  - Vestibular hyperreactivity and hyperventilation after whiplash injury.
AB  - Vestibular, oculomotor and respiratory tests were performed on 32 patients after
      whiplash injury caused by a rear-end car collision. Oculomotor functions were
      generally normal. The cervico-ocular reflex was usually absent or displayed the
      low gain typical of normal subjects. There was no nystagmic response to static
      neck torsion. The vestibulo-ocular reflex showed vestibular hyperreactivity (VH)
      in a significantly large number of cases (n = 17; 53%). The respiratory test
      results were also typical of the hyperventilation syndrome (HVS) in a
      significantly large number of cases (n = 12; 38%). The findings of VH and the HVS
      were not significantly correlated within the patient group. However, the
      combination of VH and the HVS occurred significantly more often (n = 7; 22%) than
      could be accounted for by combined false positivity. Most of the significant
      findings were due to high relative frequencies in the women: 11 out of the 17
      women (65%) showed VH, 8 (47%) had the HVS and 5 (29%) showed a combination of VH
      and the HVS. The findings were not correlated with the patient's age or the time
      interval between the accident and the examination. VH might have been the result
      of plastic adaptation to limited head mobility secondary to neck pain.
      Behavioural and emotional distress might offer alternative explanations for both
      VH and the HVS.

PMID- 8523029
TI  - Chronic brain ischemia: the contributions of Otto Binswanger and Alois Alzheimer
      to the mechanisms of vascular dementia.

PMID- 8523030
TI  - Neuroaxonal dystrophy in infantile alpha-N-acetylgalactosaminidase deficiency.
AB  - Morphologic alterations in biopsies of central and peripheral nervous tissue were
      investigated at the light-and electron-microscopic level in the first cases of
      lysosomal alpha-N-acetylgalactosaminidase deficiency. Widespread spheroid
      formation was observed in terminal and preterminal axons. Neocortical and
      peripheral autonomic axons contained tubulovesicular and lamelliform membranous
      arrays, prominent acicular clefts, and electron-dense axoplasmic matrix, the
      typical ultrastructural abnormalities corresponding to axonal spheroids in many
      inherited and acquired axonopathies. Central and peripheral membranous distal
      axonal spheroids were the only neuropathologic abnormality identified; other
      alterations resembling those in various neuronopathic lysosomal storage diseases
      were not observed. The morphologic findings and the distribution of the lesion in
      the present disorder are remarkably similar to those reported in the inherited
      infantile form of neuroaxonal dystrophy with normal alpha-N
      acetylgalactosaminidase activity (Seitelberger disease).

PMID- 8523031
TI  - EEG, CT and neurosonographic findings in patients with postischemic seizures.
AB  - Seventy-two patients with postischemic seizures were evaluated with
      electroencephalography (EEG), computerized tomography (CT) and neurosonography.
      There were 24% early-onset and 76% late-onset initial seizures. Early-onset
      seizure was more likely to be simple partial (53%), whereas late-onset seizure
      was more likely to be primarily generalized (56%). 76% early-onset and 80% late
      onset seizures were single. Status epilepticus was more frequent in early-onset
      that late-onset seizures (p = 0.023). The possibility of recurrence was greater
      in late-onset than early-onset seizures (p < 0.001). 88% patients had EEG
      abnormalities, and the most common finding was focal slowing. 75% patients had
      cerebral infarctions on CT scan, and the majority of them involved cortex. 89%
      postischemic seizures had carotid lesions which mostly were carotid plaques <
      50%. We failed to find these data to be useful in predicting the time of onset of
      initial seizures after acute ischemic stroke and recurrence.

PMID- 8523032
TI  - Expression of myotonic dystrophy protein kinase in biopsied muscles.
AB  - We present expression of myotonic dystrophy protein kinase (DM-PK) on biopsied
      muscles by immunocytochemistry using antibody against synthetic DM-PK peptide
      antigen. Immunolocalization of DM-PK was observed in neuromuscular junctions,
      muscle spindle, and sarcoplasm on both normal and DM muscles. DM-PK expression of
      sarcoplasm was present in adult normal and DM muscles. In Duchenne and Becker
      muscular dystrophies, DM-PK was intensively expressed in cytoplasm on immature
      regenerating fibers. DM-PK is initially produced in cytoplasm of regenerating
      fibers and migrates toward sarcoplasm with maturity of muscle cell.

PMID- 8523033
TI  - Retrieval from semantic memory may be normal in multiple sclerosis patients: a
      study of free word association.
AB  - Increased effort of retrieval from memory is considered to be a feature of
      cognition in subcortical neurological diseases, such as multiple sclerosis (MS).
      Free word association provides a means to investigate alterations in automatic
      and effortful retrieval. Using this procedure we investigated whether in MS free
      word association would shift from commonality towards idiosyncrasy, as a result
      of effortful, controlled retrieval. The MS group consisted of a cohort of
      outpatients, who suffered from chronic but quiescent MS. The patients responded
      with perfectly normal association patterns. Apparently, impairment of retrieval,
      or more specifically increased effort of retrieval, from memory does not hold
      true generally in MS. In patients with obvious physical handicaps (mean Kurtzke
      DSS = 4 +/- 2) we could not demonstrate abnormal associative processes.

PMID- 8523034
TI  - Spinocerebellar ataxia, type 3 (SCA3) is genetically identical to Machado-Joseph
      disease (MJD).
AB  - Spinocerebellar ataxia, type 3 (SCA3) and Machado-Joseph disease (MJD) are two
      clinically distinct representatives of the heterogeneous group of autosomal
      dominant cerebellar ataxias. Assignment of the disease genes to the same region
      of the long arm of chromosome 14 in both SCA3 and MJD suggested that these two
      disorders are genetically identical. The recent identification of a trinucleotide
      (CAG) repeat expansion in a gene underlying MJD facilitates assessment of this
      hypothesis. We analysed the MJD gene in members of a family with characteristic
      features of SCA3 and no symptoms typical of MJD. We found the same trinucleotide
      repeat expansion within the gene that was previously described in patients with
      MJD. The findings demonstrate that SCA3 and MJD are genetically identical in
      spite of their pronounced clinical differences. Furthermore, we demonstrate a
      striking variation in the copy number of the CAG repeat among affected members of
      the same family.

PMID- 8523035
TI  - Serum dehydroepiandrosterone and cortisol measurements in Huntington's chorea.
AB  - Serum levels of dehydroepiandrosterone sulfate (DHEAS), known to antagonize
      metabolic effects of glucocorticoids in animals, and cortisol (CRT), already
      shown to be related to cognitive dysfunction in man and animals, were measured in
      11 drug-free male subjects with definite Huntington's chorea (HC) and in 25 age
      matched male normal controls. Statistical difference was found between DHEAS
      serum levels (p < 0.05), CRT levels (p < 0.05) and the DHEAS/CRT ratio (p < 0.01)
      of HC subjects and normal individuals. These findings may indicate a dysfunction
      of the hypothalamic-pituitary-adrenal axis (HPAA) and possibly suggest a role of
      DHEAS as an antiglucocorticoid in HC.

PMID- 8523036
TI  - Acquired idiopathic generalized anhidrosis: clinical manifestations and
      histochemical studies.
AB  - A 40-year-old male developed complete absence of sweating except for slight
      sweating in the axillar region. Histopathologic examination of the skin revealed
      lymphocytes infiltration around the sweat glands and coarse and irregular
      arrangement of the eccrine glands. Immunohistochemical staining using anti-CD3,
      CD4, and CD8 antibodies revealed that CD3 positive cells were dominant in the
      lesion. After intensive glucocorticoid treatment, generalized sweating was almost
      completely recovered.

PMID- 8523037
TI  - Magnetic stimulation of the spinal accessory nerve: normative data and clinical
      utility in an isolated stretch-induced palsy.
AB  - We report the clinical and electrophysiological findings of isolated stretch
      induced accessory nerve palsy obtained by using conventional technique compared
      to magnetic stimulation at the base of the skull. The same methods of magnetic
      stimulation were applied in 10 healthy volunteers, to determine normal limits of
      amplitude and latency of the motor responses. The clinical features of the
      isolated spinal accessory nerve palsy are weakness of the sternocleidomastoid
      muscle and of the three portions of trapezius muscle. Most commonly reported
      etiologies include surgical manipulation and excision in the posterior triangle
      of the neck. Less frequently the cause is represented by radiation procedures,
      shoulder traction, penetrating, blunt or stretch injuries; this last etiology is
      extremely rare. The use of conventional electrophysiological methods to evaluate
      injuries of the nerves leaving the base of the skull is limited by the difficulty
      in obtaining an adequate electrical surface stimulation necessitating the use of
      needle electrodes. Moreover, conventional electrical stimulation often causes
      significant discomfort to the patient. The magnetic coli stimulation at the base
      of the skull is a new alternative painless technique that permits to elicit motor
      responses, by stimulating deeply situated nerves and, in particular, the
      accessory nerve, resulting as a useful electrodiagnostic tool.

PMID- 8523038
TI  - Positron emission tomography of reversible intellectual impairment induced by
      long-term anticholinergic therapy.
AB  - Long-term oral anticholinergic (AC) therapy can occasionally produce intellectual
      impairment. We investigated a patient with Parkinson's disease accompanied by
      intellectual impairment induced by long-term AC therapy. The intellectual
      impairment of the patient disappeared after cessation of AC therapy. Positron
      emission tomography (PET), during and after long-term oral AC therapy, revealed
      that it causes bilateral diffuse decrease of glucose metabolism in the cortex,
      basal ganglia, thalamus, hippocampus and cerebellum. Cessation of the therapy
      resulted in diffuse increase of glucose metabolism in all of the above regions.
      Cranial CT and magnetic resonance imaging (MRI) showed no abnormalities. Our
      results suggest that long-term AC therapy causes reversible bilateral diffuse
      glucose hypometabolism.

PMID- 8523039
TI  - Multiconformational composite molecular potential fields in the analysis of drug
      action. I. Methodology and first evaluation using 5-HT and histamine action as
      examples.
AB  - The quality of molecular electrostatic maps generated by non-quantum mechanical
      methods has been improved using extended electron distributions. Further
      simplification has been achieved by distilling these maps down to their energy
      extrema. A new means of defining surface interaction has been added and the
      resulting composite map has been plotted for a limited number of low-lying
      conformers of a series of agonists and antagonists of the H2 and H3 receptors and
      5-HT1A and 5-HT1D receptors. The results from the cross-comparison of these maps
      indicate their ability to distinguish the specific receptor. Interesting
      consequences of the method are that structural overlay is irrelevant, that
      several conformations may contribute to the overall binding pattern and that
      lesser pharmacological activities may be deduced from the results.

PMID- 8523040
TI  - Calculation of hydrophobic parameters directly from three-dimensional structures
      using comparative molecular field analysis.
AB  - Capacity ratio (log k') values, which are a measure of hydrophobicity, were
      calculated directly from the three-dimensional structures of 17 furans and 54
      triazines using the comparative molecular field analysis approach. The H2O probe
      and the GRID force field, including hydrogen-bond potentials, yielded excellent
      correlations with the log k' values. Moreover, the predicted values of log k'
      from 14 additional triazine analogs showed excellent agreement with log k' values
      reported in the literature. Similar results were obtained for the octanol-water
      partition coefficients (log P) of 17 furans.

PMID- 8523041
TI  - Modelling and mutation studies on the histamine H1-receptor agonist binding site
      reveal different binding modes for H1-agonists: Asp116 (TM3) has a constitutive
      role in receptor stimulation.
AB  - A modelling study has been carried out, investigating the binding of histamine
      (Hist), 2-methylhistamine (2-MeHist) and 2-phenylhistamine (2-PhHist) at two
      postulated agonistic binding sites on transmembrane domain 5 (TM5) of the
      histamine H1-receptor. For this purpose a conformational analysis study was
      performed on three particular residues of TM5, i.e., Lys200, Thr203 and Asn207,
      for which a functional role in binding has been proposed. The most favourable
      results were obtained for the interaction between Hist and the Lys200/Asn207
      pair. Therefore, Lys200 was subsequently mutated and converted to an alanine,
      resulting in a 50-fold decrease of H1-receptor stimulation by histamine.
      Altogether, the data suggest that the Lys200/Asn207 pair is important for
      activation of the H1-receptor by histamine. In contrast, analogues of 2-PhHist
      seem to belong to a distinct subclass of histamine agonists and an alternative
      mode of binding is proposed in which the 2-phenyl ring binds to the same receptor
      location as one of the aromatic rings of classical histamine H1-antagonists.
      Subsequently, the binding modes of the agonists Hist, 2-MeHist and 2-PhHist and
      the H1-antagonist cyproheptadine were evaluated in three different seven-alpha
      helical models of the H1-receptor built in homology with bacteriorhodopsin, but
      using three different alignments. Our findings suggest that the position of the
      carboxylate group of Asp116 (TM3) within the receptor pocket depends on whether
      an agonist or an antagonist binds to the protein; a conformational change of this
      aspartate residue upon agonist binding is expected to play an essential role in
      receptor stimulation.

PMID- 8523042
TI  - Applications of momentum-space similarity.
AB  - Momentum-space similarity indices were used in studies linking chemical structure
      to observed activity. These included (a) the biological activity of various
      molecules that are of interest due to their capacity for HIV inhibition; and (b)
      the hyperpolarisabilities of series of conjugated molecules. Study (a) included
      comparisons of the total valence densities of different molecules or the
      densities associated with particular molecular fragments. Study (b) involved, for
      each molecule, a comparison of the momentum-space densities of the highest
      occupied (HOMO) and lowest unoccupied (LUMO) molecular orbitals. The momentum
      space approach, which is most sensitive to features of the long-range valence
      electron density, turned out to be particularly useful for cases such as these,
      in which the physical property or biological activity has no obvious dependence
      on the bonding topology of the molecules.

PMID- 8523043
TI  - The atom assignment problem in automated de novo drug design. 1. Transferability
      of molecular fragment properties.
AB  - This paper is the first of a series which examines the problems of atom
      assignment in automated de novo drug design. In subsequent papers, a combinatoric
      optimization method for fragment placement onto 3D molecular graphs is provided.
      Molecules are built from molecular graphs by placing fragments onto the graph.
      Here we examine the transferability of atomic residual charge, by fragment
      placement, with respect to the electrostatic potential. This transferability has
      been tested on 478 molecular structures extracted from the Cambridge Structural
      Database. The correlation found between the electrostatic potential computed from
      composite fragments and that computed for the whole molecule was encouraging,
      except for extended conjugated systems.

PMID- 8523044
TI  - The atom assignment problem in automated de novo drug design. 2. A method for
      molecular graph and fragment perception.
AB  - If atom assignment onto 3D molecular graphs is to be optimized, an efficient
      scheme for placement must be developed. The strategy adopted in this paper is to
      analyze the molecular graphs in terms of cyclical and non-cyclical nodes; the
      latter are further divided into terminal and non-terminal nodes. Molecular
      fragments, from a fragments database, are described in a similar way. A canonical
      numbering scheme for the fragments and the local subgraph of the molecular graph
      enables fragments to be placed efficiently onto the molecular graph. Further
      optimization is achieved by placing similar fragments into bins using a hashing
      scheme based on the canonical numbering. The graph perception algorithm is
      illustrated in detail.

PMID- 8523045
TI  - The atom assignment problem in automated de novo drug design. 3. Algorithms for
      optimization of fragment placement onto 3D molecular graphs.
AB  - Atom assignment onto 3D molecular graphs is a combinatoric problem in discrete
      space. If atoms are to be placed efficiently on molecular graphs produced in drug
      binding sites, the assignment must be optimized. An algorithm, based on simulated
      annealing, is presented for efficient optimization of fragment placement.
      Extensive tests of the method have been performed on five ligands taken from the
      Protein Data Bank. The algorithm is presented with the ligand graph and the
      electrostatic potential as input. Self placement of molecular fragments was
      monitored as an objective test. A hydrogen-bond option was also included, to
      enable the user to highlight specific needs. The algorithm performed well in the
      optimization, with successful replications. In some cases, a modification was
      necessary to reduce the tendency to give multiple halogenated structures. This
      optimization procedure should prove useful for automated de novo drug design.

PMID- 8523046
TI  - Investigating the extension of pairwise distance pharmacophore measures to
      triplet-based descriptors.
AB  - Distances between key functional groups have been used for some time as molecular
      descriptors in 3D database screening and clustering calculations. More recently,
      a number of groups have explored triplets of molecular centers to describe key
      ligand features in terms of the properties of triangles. Three-body distances are
      attractive, since they retain more information than pairwise representations. In
      most applications, the triangular descriptors have been used to detail molecular
      shape, using all the constituent atoms or molecular surface points as descriptor
      centers. As a consequence, the database keying times were such that only single
      conformers could be considered during molecular descriptor calculations. In this
      paper we reduce the points used in the molecular description down to the key
      functional centers, as applied in 3D pharmacophore database searches. Molecular
      triplets can then be calculated which describe the relative dispositions of
      differing functional groups, made up from multiple molecular conformations of a
      given molecule. The new triplet descriptors are compared with classical pairwise
      distance measures using a variety of pharmacophores, and their potential in
      database screening, clustering and pharmacophore identification is discussed.

PMID- 8523047
TI  - The return (?) of postmastectomy radiotherapy.

PMID- 8523048
TI  - Docetaxel: current status and future prospects.

PMID- 8523049
TI  - Adequate locoregional treatment for early breast cancer may prevent secondary
      dissemination.
AB  - PURPOSE: To analyze different events that determine event-free survival (EFS) in
      a randomized trial on adjuvant radiotherapy in early breast cancer patients with
      more than 15 years of follow-up evaluation. PATIENTS AND METHODS: The trial
      included 960 patients with a unilateral, operable breast cancer. Surgery
      consisted of a modified radical mastectomy. The trial compared three arms, as
      follows: preoperative radiotherapy, postoperative radiotherapy, and no adjuvant
      treatment. Events were analyzed by a competing-risk approach. A proportional
      hazards multiple regression model was used to analyze the effects of radiotherapy
      on the risk of distant metastasis. Similar analyses were performed separately for
      node-negative [N(-)] and node-positive [N(+)] patients in the two groups that did
      not include preoperative radiotherapy. RESULTS: Radiotherapy produced a fivefold
      decrease of the risk of local recurrence (P < .0001). In N(+) patients,
      postoperative radiotherapy decreased the risk of distant dissemination (relative
      risk, 0.63). When local recurrence was introduced in the model as a time
      dependent covariate, this factor was predictive of distant dissemination (P <
      .0001) and nullified the effect of postoperative radiotherapy. This finding
      suggests that the decrease of distant metastases was related to the prevention of
      local recurrence. A similar effect was found in models that used overall survival
      as an end point. CONCLUSION: This study shows that postmastectomy radiotherapy in
      N(+) breast cancer patients may decrease the distant metastasis rate by
      preventing local recurrences and thus avoiding secondary dissemination.

PMID- 8523050
TI  - Phase II trial of docetaxel in advanced anthracycline-resistant or
      anthracenedione-resistant breast cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical efficacy and
      safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to
      doxorubicin or mitoxantrone. PATIENTS AND METHODS: Docetaxel 100 mg/m2 was
      administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients
      registered at four centers. Patients must have received at least one but no more
      than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant
      therapy). One of the regimens for metastatic breast cancer must have included an
      anthracycline or anthracenedione and the cancer must have progressed on that
      regimen. RESULTS: Objective responses were seen in 20 of 35 assessable patients
      (three complete responses [CRs] and 17 partial responses [PRs]), for an objective
      response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42
      registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the
      trial. The median response duration was 28 weeks. The most common toxicity in
      this study was grade 4 neutropenia, which occurred in 95% of patients. Other
      clinically significant nonhematologic side effects included stomatitis, skin
      reactions, neurosensory changes, asthenia, and fluid retention. Patients who
      received dexamethasone premedication had a later onset of fluid retention than
      those who did not receive dexamethasone (onset at a median cumulative docetaxel
      dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION: Docetaxel at this
      dose and schedule has a high level of antitumor activity in patients with
      treatment-refractory advanced breast cancer, and appears to be one of the most
      active agents for the treatment of this patient population.

PMID- 8523051
TI  - Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the
      management of patients with anthracycline-resistant metastatic breast cancer.
AB  - PURPOSE: To determine the efficacy (objective response rate and duration of
      response and survival) and toxicity of docetaxel in patients with strictly
      defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND
      METHODS: Thirty-five patients with bidimensionally measurable MBC who had
      progressive disease while receiving anthracycline-containing chemotherapy were
      registered onto the phase II trial. Docetaxel was administered at a dose of 100
      mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable
      for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved
      a partial response. The median times to disease progression and survival duration
      were 7.5 and 13.5 months, respectively, for responding patients. The median
      overall survival duration was 9 months. Two hundred eight cycles (median, five)
      of docetaxel were administered. Neutropenia with less than 500 cells/microL
      developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208
      cycles and in 18 (51%) of 35 patients, including one treatment-related death.
      Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions
      in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed
      in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the
      highest reported antitumor activity in anthracycline-resistant MBC. High
      objective response rates were seen in patients with visceral-dominant
      involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel
      is associated with severe but reversible neutropenia, asthenia, and cumulative
      dose-related fluid retention. Dexamethasone decreased the frequency and severity
      of skin toxicity and appeared to ameliorate fluid retention.

PMID- 8523052
TI  - Phase II trial of docetaxel in patients with advanced cutaneous malignant
      melanoma previously untreated with chemotherapy.
AB  - PURPOSE: A phase II study was undertaken to determine the efficacy of docetaxel
      in patients with metastatic malignant melanoma. PATIENTS AND METHODS: Between
      June 1992 and March 1994, 40 patients with metastatic malignant melanoma and no
      prior chemotherapy were treated with docetaxel 100 mg/m2 administered
      intravenously over 1 hour every 21 days. None of the patients had brain
      metastasis. Toxicity and follow-up data are provided. RESULTS: One patient had a
      histologically confirmed complete response that lasted for 14+ months. Four
      patients had partial responses, bringing the overall response rate to 12.5% (95%
      confidence interval [CI], 6% to 30%). A patient with a partial response had a
      single chest-wall metastasis and was rendered free of disease surgically after a
      maximal response to docetaxel and remained free of tumor recurrence after 18+
      months. Tumor was stabilized in 22 patients. The overall median survival time was
      13 months. The main hematologic toxicity was neutropenia, which was severe but
      transient. Peripheral neuropathy was the limiting nonhematologic toxicity in
      three patients. Other important toxicities included cutaneous toxicity, fluid
      retention, oral mucositis, and hypersensitivity reactions. Preadministration of
      dexamethasone and diphenhydramine reduced the incidence of hypersensitivity
      reactions, cutaneous toxicities, and fluid retention. CONCLUSION: Docetaxel has
      definite but low-level activity against malignant melanoma. Further investigation
      of this drug should be conducted in multidrug combination programs.

PMID- 8523053
TI  - Tamoxifen and toremifene lower serum cholesterol by inhibition of delta 8
      cholesterol conversion to lathosterol in women with breast cancer.
AB  - PURPOSE: Long-term effects of tamoxifen and toremifene, a new antiestrogen that
      closely resembles tamoxifen, were investigated on serum lipids and cholesterol
      metabolism. PATIENTS AND METHODS: The study group consisted of 24 postmenopausal
      Finnish women with advanced breast cancer from an international multicenter study
      of 415 patients. Cholesterol metabolism was evaluated by measuring the
      cholesterol precursor (delta 8-cholestenol, desmosterol, and lathosterol,
      reflecting cholesterol synthesis) and plant sterol (markers of cholesterol
      absorption) and cholestanol levels by gas-liquid chromatography. RESULTS:
      Tamoxifen and toremifene lowered significantly serum low-density lipoprotein
      (LDL) cholesterol levels after 12 months of treatment by 16% and 15%, with no
      change in high-density lipoprotein (HDL) cholesterol or serum triglyceride
      levels. Serum delta 8-cholestenol was increased 40- and 55-fold during toremifene
      and tamoxifen treatment, respectively, while the increase of desmosterol less
      than doubled and was lacking for lathosterol by toremifene. Plant sterols and
      cholestanol were only inconsistently increased in serum. CONCLUSION: Tamoxifen
      and toremifene inhibit the conversion of delta 8-cholestenol to lathosterol so
      that serum total and LDL cholesterol levels are lowered by downregulation of
      cholesterol synthesis. Thus, inhibition of the delta 8-isomerase may be the major
      hypolipidemic effect of these agents. Reduced risk of coronary artery disease
      will probably occur also during long-term toremifene treatment, because the drug
      reduces cholesterol and its synthesis, similarly to tamoxifen.

PMID- 8523054
TI  - Does administration of chemotherapy before radiotherapy in breast cancer patients
      treated with conservative surgery negatively impact local control?
AB  - PURPOSE: To determine if a delay of irradiation to the intact breast for
      administration of adjuvant chemotherapy results in increased local recurrence in
      breast cancer. PATIENTS AND METHODS: The records of 262 women with 264 cases of
      breast cancer were reviewed. Group I contained 105 patients treated with
      conservative surgery, chemotherapy, and radiotherapy. Group II contained 157
      patients (used as a concurrent control) treated with conservative surgery and
      radiotherapy only. Eighty-nine percent of subjects in group I received all
      chemotherapy before radiotherapy. Fifty-eight percent of patients received
      hormone therapy. Seventy-one percent of patients had negative surgical margins,
      and 74% had negative lymph nodes. For group I, conservative surgery-radiotherapy
      intervals in months were less than 1 (five, 5%), > or = 1 to less than 3 (10,
      9%), > or = 1 to less 6 (48, 46%), and > or = 6 (42, 40%), mean of 5. For group
      II, the intervals were less than 1 (20, 13%), > or = 1 to less than 3 (123, 79%),
      > or = 3 to less than 6 (11, 7%), and > or = 6 (two, 1%), mean of 1.5. RESULTS:
      Thirty patients (11.5%) have disease recurrence (19 distant [6%] and 12 local
      [5%]). There were no significant differences in local recurrence (group I, four
      [4%]; group II, eight [5%]; difference not significant). There were no
      significant differences in local recurrence in any surgery-radiotherapy interval
      within each group. Although we found marginal increases in the percentage of
      local recurrences in group I patients (with prolonged surgery-radiotherapy
      intervals) who had positive margins, positive lymph nodes, and tumor size more
      than 2 cm versus group II (without prolonged surgery-radiotherapy intervals),
      these results were not significant. CONCLUSION: We could not identify any surgery
      radiotherapy interval that resulted in increased local recurrence if radiotherapy
      was delayed for administration of adjuvant chemotherapy in breast cancer
      patients. Because of the heterogenous population of breast cancer patients, our
      results also support the need for further study to determine the optimum
      integration of radiotherapy and chemotherapy in the management of the
      conservatively treated breast.

PMID- 8523055
TI  - High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non
      Hodgkin's lymphoma: a dose-finding pilot study.
AB  - PURPOSE: To purpose of this study was to develop a more effective approach to the
      treatment of patients with poor-prognosis aggressive non-Hodgkin's lymphoma
      (NHL). PATIENTS AND METHODS: Thirty newly diagnosed patients with bulky (> or =
      10 cm) advanced-stage aggressive NHL were enrolled onto a pilot study. The study
      was designed to determine the maximum-tolerated dosages (MTD) of cyclophosphamide
      and doxorubicin that could be used in a high-dose cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP) regimen with granulocyte colony-stimulating
      factor (G-CSF) support and to assess preliminarily the efficacy of the regimen.
      RESULTS: In the initial dose-finding portion of the study, cumulative
      thrombocytopenia was the dose-limiting toxicity. At the MTD, the regimen included
      four 21-day cycles of cyclophosphamide 4 gm/m2, doxorubicin 70 mg/m2, vincristine
      2 mg, and prednisone 100 mg for 5 days with mesna and G-CSF support. At the MTD,
      65% of treatment cycles were complicated by febrile neutropenia, 84% of patients
      received at least one platelet transfusion for platelet counts less than
      20,000/microL, and there was one treatment-related death. Nineteen of 22 (86%;
      90% confidence interval [CI], 68 to 96) patients treated at the MTD achieved an
      initial complete response (CR), and 79% (90% CI, 58 to 92) of the complete
      responders and 69% of all patients remain progression-free with 20 months median
      follow-up. CONCLUSION: The high-dose CHOP regimen may be an effective alternative
      for patients with poor-prognosis aggressive NHL.

PMID- 8523056
TI  - Role of recombinant interferon alfa-2a maintenance in patients with limited-stage
      small-cell lung cancer responding to concurrent chemoradiation: a Southwest
      Oncology Group study.
AB  - PURPOSE: This study was designed to determine if recombinant interferon alfa-2a
      (rIFN alpha-2a) could prolong remission duration and/or survival in patients with
      limited-stage small-cell lung cancer (SCLC) who achieved an objective response to
      chemoradiotherapy. A secondary end point was to assess the toxicity of chronic
      IFN administration. PATIENTS AND METHODS: One hundred seventy-one of 215 eligible
      patients achieved an objective response and were eligible to receive rIFN alpha
      2a (3 million units [MU]/m2 subcutaneously three times per week escalated to 9
      MU/m2 as tolerated) or observation for 2 years. RESULTS: One hundred thirty-two
      of 140 registered patients were eligible. Sixty-four patients were randomized to
      receive IFN and 68 to observation alone. The median time from randomization to
      progression was 9 months on the IFN arm and 10 months on the observation arm (P =
      .72). The overall median survival time was 16 months on the observation arm
      versus 13 months on the IFN arm (P = .77). Significant toxicities occurred in the
      rIFN alpha-2a arm. Grade 3 or higher toxicities included malaise, fatigue, and/or
      lethargy (30%), leukopenia (14%), neutropenia (13%), dyspnea (13%), nausea (11%),
      and respiratory infection (6%). Forty-three patients discontinued treatment due
      to intolerable side effects. CONCLUSION: rIFN alpha-2a in the dose and schedule
      used in this study failed to prolong response duration or survival in patients
      with limited-stage SCLC who had previously responded to an induction
      chemoradiotherapy program. Failure may have been partly related to poor tolerance
      and inability to complete therapy.

PMID- 8523057
TI  - Association of malignant brain tumors and cancers of other sites.
AB  - PURPOSE: We conducted an exploratory study of brain tumors that occurred as a
      second primary malignancy to identify potential risk factors for brain tumors.
      METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER)
      Program, we calculated the sex-specific standardized incidence ratio (SIR),
      adjusted to age and time period, as an estimate of the relative risk (RR) of
      developing a second primary brain tumor following other cancers. RESULTS: We
      found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7;
      95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to
      3.2); this effect was present for both astrocytoma and glioblastoma multiforme.
      Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8
      to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal
      cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0
      to 1.9) in women. The highest RR observed in this study was for CNS lymphoma
      following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0).
      CONCLUSION: The associations of brain tumors with bladder, colorectal, and
      endometrial cancers in women, and an increased occurrence of CNS lymphoma as a
      second malignancy in men, are new findings that have not been described
      previously.

PMID- 8523058
TI  - Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage
      II/Dukes' B2 colon cancer.
AB  - PURPOSE: To determine the effectiveness of fluorouracil plus levamisole
      administered postoperatively to patients with resected stage II (Dukes' B2) colon
      cancer. PATIENTS AND METHODS: This randomized controlled clinical trial (INT
      0035) was performed by National Cancer Institute-sponsored cancer clinical trials
      cooperative groups. Patients were assigned to observation only or to fluorouracil
      (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly
      for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated
      every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side
      effects were assessed. RESULTS: Three hundred eighteen eligible patients were
      analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole
      reduced the recurrence rate by 31%, although this trend was not statistically
      significant (P = .10). A total of 87 patients died: 43 on observation and 44 on
      fluorouracil plus levamisole. Disparity between effects on recurrence rate and
      overall survival is partially explained by a higher rate of non-colon cancer
      related deaths on fluorouracil plus levamisole (15 v seven) and by the effects of
      salvage surgery with curative intent. Of seven patients with recurrence who were
      rendered disease-free by salvage surgery, six were on the observation arm. As was
      observed in patients treated with fluorouracil plus levamisole for stage III
      disease, toxicity was acceptable and compliance was excellent. CONCLUSION:
      Fluorouracil plus levamisole is tolerable and accepted as standard surgical
      adjuvant therapy for patients with stage III colon cancer, but the data from this
      study in stage II patients suggest a decreased relapse rate without a significant
      improvement in survival.

PMID- 8523059
TI  - Evaluation of prostate-specific antigen as a surrogate marker for response of
      hormone-refractory prostate cancer to suramin therapy.
AB  - PURPOSE: We evaluated the surrogate role of serum prostate-specific antigen (PSA)
      using prospectively collected information from patients with hormone-refractory
      prostate cancer (HRPC) treated with suramin. MATERIALS AND METHODS: Data from 103
      patients were analyzed using survival analysis, exploratory analysis, and
      regression analysis. RESULTS: There was a significant survival difference between
      groups of patients with a PSA decrease of < or = 0% or greater than 0% (P =
      .018). There were no significant overall survival differences between groups of
      patients with PSA decreases less than 50% or > or = 50% and less than 75% or > or
      = 75%. Tree-based modeling did not define a specific threshold percentage PSA
      change as a response criterion. For a response of 1-year survival, sensitivity
      increased (0.91 v 0.69), but specificity decreased (0.37 v 0.62), with a 75%
      versus 50% PSA decrease used as classification criterion. Differences between the
      area under the receiver-operating curves (ROCs) with 50% and 75% PSA decreases as
      threshold values were small. For a response of 1-year survival, attributable
      proportions were 0.38 and 0.68, respectively, with 50% and 75% PSA decreases as
      threshold values. When pretreatment variables were assessed by Cox proportional
      hazards model, hemoglobin level was the most significant predictor of survival.
      When percentage PSA change was included in the model, hemoglobin level remained
      the most significant factor, but percentage PSA change was also a weak, but
      statistically significant, factor. PSA was a weak, but statistically significant,
      predictor of survival in Cox proportional hazards model with PSA as a time
      variant covariate. CONCLUSION: Reduction in PSA level has weak prognostic
      significance with respect to survival in HRPC patients, but, currently, PSA
      reduction cannot be used as a reliable response criterion to evaluate treatment
      efficacy in individual patients. Prospective, randomized studies, including
      prospective measurement of other indices related to symptomatic clinical
      benefits, are required.

PMID- 8523060
TI  - Steady-state levels and bone marrow toxicity of etoposide in children and
      infants: does etoposide require age-dependent dose calculation?
AB  - PURPOSE: Most pediatric treatment protocols specify dose calculations for
      cytostatic drugs based on body-surface area (BSA). However, for children less
      than 1 year of age, calculation guidelines vary. Normally, reduced dosages are
      recommended with calculations based on body weight (BW). However, the optimal
      dose for infants should take age-dependent and drug-specific pharmacokinetic
      parameters into account. PATIENTS AND METHODS: The current investigation focused
      on the effects of different dose-reduction rules on the steady-state levels (Css)
      of etoposide and related bone marrow toxicity. One hundred seventy three
      treatment courses in 78 children on a 96-hour continuous infusion schedule were
      monitored for Css (determined by high-performance liquid chromatography [HPLC]),
      and 100 courses were documented in detail with regard to dose calculation (125
      mg/m2, 4.17/kg, or 2/3 x 4.17/kg) and toxicity. RESULTS: Dose calculation on the
      basis of BSA led to Css of 4.9 +/- 1.2 micrograms/mL, which on the basis of BW
      was 3.5 +/- 1.1 micrograms/mL and 1.95 +/- 0.6 micrograms/mL (2/3.kg-dose),
      respectively. However, conversion of the latter levels to those expected with the
      regular square-meter-dose, resulted in values of 4.7 +/- 1.4 micrograms/mL and
      4.2 +/- 1.2 micrograms/mL (/125 mg/m2). Lower etoposide Css levels resulted in
      less pronounced thrombocyte and WBC nadirs in the respective groups. The dose
      calculation rules for infants, therefore, decreased both dose-intensity and
      related toxicity. Etoposide clearance rates related to BW (0.8 +/- 0.3 mL/min/kg)
      or BW (19 +/- 6 mL/min/m2) did not show any differences between children and
      infants, even in the age range of 3 to 12 months. CONCLUSION: In the case of
      etoposide, special dose-calculation guidelines for infants are not substantiated
      by age-dependent pharmacokinetics or tolerance.

PMID- 8523061
TI  - Phase I feasibility and pharmacologic study of weekly intraperitoneal paclitaxel:
      a Gynecologic Oncology Group pilot Study.
AB  - PURPOSE: This study was designed to define the maximum-tolerated dose (MTD) and
      pharmacology of paclitaxel administered by the intraperitoneal (IP) route on a
      weekly schedule. PATIENTS AND METHODS: Thirty-three patients with residual
      ovarian cancer following standard chemotherapy were entered onto this phase I
      trial. Patients were treated weekly with IP paclitaxel administered in 2 L of
      normal saline following premedication. Patients with nonassessable disease
      received 16 weekly courses. The initial dose level was 20 mg/m2/wk. There was no
      intrapatient dose escalation. RESULTS: Multiple grade 2 toxicities were observed
      at the 75-mg/m2/wk dose level. These toxicities included abdominal pain, nausea,
      vomiting, leukopenia, and fatigue. One episode of grade 4 vomiting thought to be
      secondary to a transient partial small-bowel obstruction occurred at this dose
      level. At dose levels > or = 60 to 65 mg/m2, pharmacology studies documented the
      persistence of significant IP paclitaxel levels 1 week after drug administration,
      suggesting very slow peritoneal clearance and continuous exposure of the
      peritoneal cavity to active concentrations of paclitaxel. Low plasma paclitaxel
      concentrations were detected in the majority of patients treated at dose levels >
      or = 55 mg/m2. CONCLUSION: Paclitaxel can be delivered by the IP route on a
      weekly schedule with both an acceptable toxicity profile and a major
      pharmacokinetic advantage for cavity exposure. The recommended dose and schedule
      for phase II study of IP paclitaxel is 60 to 65 mg/m2 weekly.

PMID- 8523062
TI  - Phase I clinical and pharmacokinetic study of leucovorin and infusional hepatic
      arterial fluorouracil.
AB  - PURPOSE: A phase I and pharmacokinetic trial was performed between October 1993
      and June 1994 to determine the maximum-tolerated dose of hepatic arterial
      infusion (HAI) of fluorouracil (5-FU) and intravenous (IV) leucovorin (folinic
      acid; FA) in patients with hepatic metastases from colorectal cancer. PATIENTS
      AND METHODS: Forty-three patients received 310 courses of HAI chemotherapy
      administered over 48 hours every 2 weeks. The regimen consisted of FA 200 mg/m2
      by IV infusion over 2 hours, followed by a loading dose of 5-FU 400 mg/m2 by HAI
      over 15 minutes, followed by a 22-hour infusion of 5-FU at doses ranging from 0.8
      to 1.84 g/m2, with identical chemotherapy on day 2. Pharmacokinetic studies were
      performed to determine peak and steady-state plasma concentrations (Css) of 5-FU.
      RESULTS: Severe diarrhea and cardiac and neurologic toxicity were dose-limiting
      at 1.84 g/m2. The recommended dose for the 22-hour component of the schedule was
      1.6 g/m2 and was associated with tolerable toxicity. A Css of 2.2 +/- 0.8 mumol/L
      for 5-FU was achieved on the recommended schedule, which compares favorably with
      conventional IV 5-FU regimens. Among 30 patients assessable for response, there
      were four complete responses and seven partial responses, and 12 patients with
      stable disease and seven with progressive disease, reported after 3 months (ie,
      six cycles) of therapy. CONCLUSION: A regimen that combines 5-FU and FA has been
      identified for regional chemotherapy in patients with hepatic metastases from
      colorectal cancer. The systemic levels of 5-FU achieved are similar to the
      conventional IV de Gramont regimen using an identical schedule of 5-FU and FA,
      which implies that this chemotherapy has the best of both worlds, ie, a regional
      advantage in delivering high drug concentrations to the target organ with
      adequate systemic cover for extrahepatic micrometastases.

PMID- 8523063
TI  - Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow
      transplantation for myelodysplasia.
AB  - PURPOSE: A non-radiation-containing regimen of busulfan and cyclophosphamide
      (BU/CY) was evaluated for toxicity, relapse, and long-term survival in patients
      who received allogeneic bone marrow transplantation (BMT) for myelodysplasia
      (MDS). PATIENTS AND METHODS: Thirty-eight patients with MDS, including eight with
      therapy-related MDS, were prepared for BMT using BU/CY. RESULTS: Fourteen
      patients remain in first remission 18 to 60 months posttransplant. Five patients
      relapsed after BMT, and four of these patients died. Eight additional patients
      died of acute or chronic graft-versus-host disease (GVHD), and 11 died of regimen
      related toxicity, primarily systemic mycoses. Overall survival rate at 2 years
      was 45% (95% confidence interval [CI], 0.30 to 0.61), with a 24% probability of
      relapse (95% CI, 0.10 to 0.49). Regimen-related toxicity was manifested primarily
      as hepatic dysfunction in 72% of patients, with 16% developing overt
      venoocclusive disease (VOD). CONCLUSION: Non-radiation-containing preparative
      regimens offer long-term survival in allogeneic BMT for MDS that is comparable to
      that of radiation-containing regimens, and are useful in patients with therapy
      related MDS. Monitoring BU levels may reduce regimen-related mortality and
      improve survival.

PMID- 8523064
TI  - Presidential address. May 22, 1995 Thirty-First Annual Meeting of the American
      Society of Clinical Oncology.

PMID- 8523065
TI  - Satellite symposium on brain tumours. Ottawa, Canada, September 24-25, 1994.
      Proceedings.

PMID- 8523066
TI  - Cyclophosphamide therapy of medulloblastoma: from the laboratory to the clinic
      and back again (and again and again).
AB  - Medulloblastoma, the most common malignancy of childhood, was originally shown to
      be sensitive to cyclophosphamide in 1981. We have used combined laboratory and
      clinical investigations to demonstrate the synergy of cyclophosphamide and
      vincristine in the treatment of this tumor, the therapeutic gain associated with
      escalation of the dosage of cyclophosphamide, the consequence of and mechanisms
      underlying resistance of medulloblastoma to cyclophosphamide, the emerging
      importance of the neuraxis as a site of relapse of medulloblastoma, and newer
      approaches, including intrathecal 4-hydroperoxycyclophosphamide and busulfan, to
      treat neuraxis disease. These studies serve as a paradigm for laboratory-clinical
      translational research.

PMID- 8523067
TI  - Phase I studies of treatment of malignant gliomas and neoplastic meningitis with
      131I-radiolabeled monoclonal antibodies anti-tenascin 81C6 and anti-chondroitin
      proteoglycan sulfate Me1-14 F (ab')2--a preliminary report.
AB  - The advent of monoclonal antibody (MAb) technology has made Ehrlich's postulate
      of the 'magic bullet' an attainable goal. Although specific localization of
      polyvalent antibodies to human gliomas was demonstrated in the 1960s, the lack of
      specific, high affinity antibody populations and of defined target antigens of
      sufficient density precluded therapeutic applications. Not until the
      identification of operationally specific tumor-associated antigens (present in
      tumor tissue but not normal central nervous system tissue); production of
      homogeneous, high affinity MAbs to such antigens; and the use of compartmental
      administration (intrathecal or intracystic), has the promise of passive
      immunotherapy of primary and metastatic central nervous system neoplasms been
      recognized. We report here preliminary data from Phase I studies of the
      compartmental administration of the anti-tenascin MAb 81C6 and F(ab2)2 fragments
      of MAb Me1-14, which recognizes the proteoglycan chondroitin sulfate-associated
      protein of gliomas and melanomas, to patients with primary central nervous system
      tumors or tumors metastatic to the central nervous system. Phase I dose
      escalation studies of intracystically administered 131I-labeled anti-tenascin MAb
      81C6 to either spontaneous cysts of recurrent gliomas or surgically created
      cystic resection cavities have resulted in striking responses. Of five patients
      with recurrent cystic gliomas treated, four had partial responses, clinically or
      radiographically. Similarly, in patients with surgically created resection
      cavities, a partial response at the treatment site and extended stable disease
      status has been obtained following intracystic administration of 131I-labeled
      81C6. No evidence of hematologic or neurologic toxicity has been observed in
      either patient population, with the exception of transient exacerbation of a pre
      existing seizure disorder in a single patient. Dosimetry calculations indicated
      high intracystic retention for four to six weeks with little or no systemic
      dissemination; estimated total doses intracystically ranged from 12,700-70,290
      rad. Intrathecal administration of labeled MAbs to patients with neoplastic
      meningitis is more difficult to assess in terms of clinical responsiveness. Of
      patients so treated with either 131I-labeled 81C6 or 131I-labeled Me1-14 (F(ab)2,
      cerebrospinal fluid and radiographic responses have been achieved, and survival
      prolongation through maintenance of stable disease has been observed in several
      cases. Initial results from pHase I dose escalation trials are encouraging in
      terms of the proportion of cases of disease stabilization and partial and
      complete responses obtained. Importantly, neurotoxicity has been virtually
      nonexistent, and hematologic toxicity rare and rapidly responsive to
      treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8523068
TI  - Central neuronal tumors in childhood: relationship to dysplasia.
AB  - A survey of 1,500 brain tumors at The Hospital for Sick Children in Toronto
      reveals that about 20-25% of tumors demonstrate some form of neuronal
      differentiation. At one end of the spectrum are the well-defined ganglionic
      tumors, sometimes difficult to differentiate from cortical dysplasia. At the
      other extreme are primitive neuroectodermal tumors with neuronal differentiation
      often confined to immunohistochemical observations. Of the total number of
      tumors, approximately 5% have a definitive ganglionic component, the majority
      being ganglioglioma, and others include dysembryoplastic neuroepithelial tumor,
      infantile ganglioglioma, paraganglioma, central neurocytoma, and gangliocytoma.
      Some tumors such as subependymal giant cell tumor associated with tuberous
      sclerosis occasionally have evidence of neuronal differentiation with
      immunoreactivity with antisera to neuron-specific enolase and negativity with
      antisera to GFAP. In children with epilepsy, improved brain imaging has
      identified lesions which on examination following temporal lobectomy show varying
      degrees of cortical dysplasia. At this site, there is also a high incidence of
      gangliogliomas. Is there a relationship between cortical dysplasia and neuronal
      tumors? Following a primary induction event during development, embryonal
      dysplasia and/or neoplasia may occur. The lesion may be malformative as in
      unilateral megalencephaly, hamartomatous as in tuberous sclerosis, neoplastic as
      in congenital tumors, or a combination of malformative and neoplastic.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8523069
TI  - Central nervous system atypical teratoid/rhabdoid tumors of infancy and
      childhood.
AB  - Clinical and morphological features of an apparently unique, biologically
      aggressive central nervous system tumor in 32 infants and children are presented.
      This neoplasm is formed wholly or partly by rhabdoid cells, areas resembling
      typical primitive neuroectodermal tumor, and, less frequently, malignant
      mesenchymal and/or epithelial tissue. The tumor has been named atypical
      teratoid/rhabdoid tumor (ATT/RhT) and is regarded as a unique class of primary
      central nervous system (CNS) tumors. It occurs most commonly in infants less than
      two years of age, has often metastasized throughout the CNS at presentation, dose
      not respond to therapy and causes death less than a year after diagnosis. These
      tumors may occur in any CNS site but almost 60% are located in the cerebellum.
      The most common chromosomal abnormality involves chromosome 22.

PMID- 8523070
TI  - Oligodendrogliomas: clinicopathological correlations.

PMID- 8523071
TI  - Revising the World Health Organization (WHO) Blue Book--'Histological typing of
      tumours of the central nervous system'.

PMID- 8523072
TI  - Primary central nervous system lymphomas--new pathological developments.
AB  - Primary central nervous system lymphomas (PCNSL) show increased incidence both in
      immunocompromised high-risk groups and in the general population. They are
      extranodal diffuse non-Hodgkin's lymphomas with a morphology similar to systemic
      lymphomas, but differ in their biological and molecular behaviour. The majority
      are large B-cell variants of high-grade malignancy; low-grade subtypes and T-cell
      lymphomas are rare; up to 50% remain unclassified according to the New Working
      Formulation and updated Kiel classification. Monoclonality of immunoglobulin
      receptor gene rearrangement can be diagnostically useful. The pathogenesis of
      PCNSL is obscure. Epstein-Barr virus (EBV) genome/proteins expression in two
      thirds of HIV-related PCNSL but only in 15% of those in immunocompetent patients
      suggest different EBV latency stages in both types; human herpesvirus type 6 does
      not appear to play a pathogenic role. Comparison of expression patterns of
      integrin chains and adhesion molecules are very similar for PCNSL and nodal
      lymphomas suggesting that they are not selective mediators of lymphoma cell
      homing to the brain. In HIV-negative PCNSL they appear not to be influenced by
      EBV. Studies of protooncogenes (bcl-1 and bcl-2 genes) revealed no rearrangement
      in PCNSL, suggesting that they are not involved in the pathogenesis of PCNSL that
      probably do not differ cytogenetically from nodal B-cell lymphomas. Since most of
      the currently known molecular parameters are probably not the primary pathogenic
      events, the molecular genetics and pathogenesis of PCNSL are still to be
      elucidated.

PMID- 8523073
TI  - Genetic alterations in gliomas.

PMID- 8523074
TI  - Prognostic implications of chromosome 17p deletions in human medulloblastomas.
AB  - DNA derived from medulloblastoma biopsies was analyzed to determine if deletions
      of the 17p region, mutations of the TP53 gene, or amplification of the c-myc, N
      myc, EGFR (epidermal growth factor receptor), or MDM2 (murine double-minute-2)
      genes was indicative of a poor prognosis. Loss of heterozygosity for 17p,
      observed in 8/28 (29%) paired samples, was associated with a shortened survival
      period (p = 0.045 by the logrank test). TP53 mutations occurred in 2/46 (4.3%)
      tumor samples. c-myc Amplification was seen in 3/43 (6.9%) cases, while none of
      the tumors contained amplified N-myc, EGFR, or MDM2 genes. These results
      demonstrate that, while only rare medulloblastomas contain TP53 gene mutations or
      amplification of the c-myc gene, loss of heterozygosity on chromosome 17p is
      indicative of a significantly worse prognosis among patients with these tumors.
      Further, these results provide a strong impetus for a prospective analysis of
      loss of heterozygosity in a cooperative group setting, which would include tumor
      staging, a selection of treatment modalities, and multivariate analyses.

PMID- 8523075
TI  - Molecular cytogenetic quantitation of gains and losses of genetic material from
      human gliomas.
AB  - The unregulated growth that is characteristic of human malignant gliomas is
      accompanied by, and may result from, losses and/or gains of genetic material.
      Understanding the mechanisms that underlie how particular genetic aberrations
      cause dysfunctional growth will help elucidate the pathogenesis of this disease.
      Two techniques are proving useful in evaluating the clinical relevance of
      specific genetic aberrations in malignant gliomas. Fluorescence in situ
      hybridization (FISH) permits direct visualization of gains and losses of genetic
      material in single cells and quantitation of cellular subpopulations that have
      particular genetic aberrations. Comparative genomic hybridization can identify
      regions of genetic gain and loss in tumor DNA.

PMID- 8523076
TI  - The neuroepithelial stem cell concept: implications for neuro-oncology.

PMID- 8523077
TI  - Lineage, migration, and fate determination of postnatal subventricular zone cells
      in the mammalian CNS.
AB  - We have been examining the developmental fates and migrational patterns of the
      immature cells in the subventricular zone (SVZ) of the mammalian forebrain by
      labeling postnatal rat SVZ cells by stereotactic injection of replication
      deficient murine retroviruses bearing reporter genes. SVZ cells migrate into
      adjacent white matter, cortex, and striatum, and differentiate into astrocytes
      and oligodendrocytes. In white matter, they largely differentiate into
      oligodendrocytes, whereas in gray matter, they differentiate into both
      oligodendrocytes and astrocytes. In vitro, SVZ cells are multipotential, able to
      generate both types of glia, as well as neurons. We infer that developmental
      fates are in part controlled by important environmental cues that the cells
      encounter during their migration.

PMID- 8523078
TI  - Ganglioside modulation of the PDGF receptor. A model for ganglioside functions.
AB  - Gangliosides are a family of glycolipids that are present at the cell surface of
      all mammalian cells. Patterns of gangliosides are different in gliomas than
      normal brain, and exogenously added gangliosides affect the growth of cultured
      glioma cells. Gangliosides inhibit the activities of several kinases, including
      protein kinase C (PKC) and cAMP-kinase. U-1242 MG cells (derived from a human
      malignant glioma) have receptors for platelet-derived growth factor (PDGF) that
      become phosphorylated on tyrosine when exposed to PDGF. Exposure of these cells
      to PDGF also causes an increase in intracellular calcium concentration ([Ca2+]i)
      and induces a translocation of PKC to the membrane. Preincubation of U-1242 MG
      cells with several species of gangliosides inhibits the increase in ([Ca2+]i) and
      PKC translocation in response to PDGF, but GM3 is much less effective than other
      species tested. This is due to a lack of activation of the receptor tyrosine
      kinase as monitored by phosphorylation of the receptor on tyrosine residues, but
      is not due to an inhibition of binding of PDGF to its receptors. The lack of
      activation of the PDGF receptor tyrosine kinase is due to an inhibition of
      dimerization of the receptor monomers by gangliosides GM1, GM2, GD1a, GT1b, but
      not GM3. Therefore, gangliosides may be involved in coordinating the activities
      of multiple trophic factors simultaneously acting on a cell by regulating the
      dimerization of their respective receptor monomers.

PMID- 8523079
TI  - Degradation of collagen type IV by C6 astrocytoma cells.
AB  - The key event associated with the initiation of angiogenesis is the localized
      degradation of the vascular basement membrane. Because of its complex structure,
      any remodelling and/or modification of the basement membrane must involve the co
      ordinated function of a number of different enzyme systems. Type IV collagen is a
      major protein component (60-90%) of the basement membrane and its degradation is
      crucial to the initiation of angiogenesis. This study has focused on the
      mechanisms by which C6 astrocytoma cells degrade human type IV collagen. C6
      astrocytoma cells use components of two major degradative pathways to degrade
      collagen type IV. The major matrix metalloproteinase identified is the activated
      form (68-KDa) of gelatinase A (72-KDa matrix metalloproteinase) and a serine
      sensitive 1000-KDa collagenase type IV degrading activity which appears to have
      the characteristics of a novel extracellular proteasome.

PMID- 8523080
TI  - Computer-assisted analysis of the microvasculature in untreated glioblastomas.

PMID- 8523081
TI  - Interactions of glioma cells and extracellular matrix.
AB  - The communication between tumor cells and extracellular matrix (ECM) is
      responsible for clinically important features of malignant gliomas, such as
      cerebral invasion and leptomeningeal spread. The synthesis of ECM components, ECM
      degrading activities and ECM receptors as well as the interaction between ECM
      components and their receptors represents the molecular basis for these
      processes. Recent studies have shown that proteases and integrins, the major
      group of ECM receptors, may be over-expressed by astrocytic tumor cells.
      Furthermore, integrins and the hyaluronate receptor CD44 have been found to be
      involved in adhesion and basement membrane invasion of glioma cells. Critical
      issues which are poorly understood so far include the ECM composition of the
      normal human brain and of brain tumors, the function of individual ECM components
      and receptors in a neuro-oncological context, and the molecular processes
      mediating the diffuse invasion of glioma cells into the brain.

PMID- 8523082
TI  - Proliferation markers in gliomas: a comparison of BUDR, KI-67, and MIB-1.

PMID- 8523083
TI  - External beam radiotherapy: hard facts and painful realities.
AB  - In comparison to whole brain radiotherapy, local field radiotherapy in a
      consecutive series of 100 patients with malignant astrocytoma resulted in
      remarkably less toxicity. Survivorship is not different; the advantage is limited
      to the 7% long term survivors (defined as living 100% or more beyond median)
      since toxicity from brain radiation does not occur until a year or more after
      treatment.

PMID- 8523084
TI  - New therapies of primary CNS lymphomas and oligodendrogliomas.

PMID- 8523085
TI  - Glutathione S-transferases and cytochrome P450 detoxifying enzyme distribution in
      human cerebral glioma.
AB  - Malignant astrocytomas are frequently resistant to cytotoxic chemotherapy. A
      possible mechanism of chemoresistance is drug inactivation within malignant
      astrocytes by detoxifying enzymes (glutathione transferases (GST) and cytochrome
      P450's). The aim of this study was to assess whether there was differential
      expression of these detoxifying enzymes in the central nervous system and any
      relationship to histological grade (WHO) of the tumours. Immunostaining was
      performed in 30 consecutive glioma samples, using class specific polyclonal
      antibodies to subtypes of GST (pi, alpha, mu) and to human cytochrome P450
      reductase. GST immunostaining was evident in astrocytes and endothelium but not
      neurones or oligodendrocytes in normal brain. Immunostaining for GST increased in
      intensity from well differentiated tumours to glioblastoma. Staining was least
      evident in surrounding normal brain, strong in reactive astrocytes and astrocytic
      tumour cells and very intense in gemistocytic and giant tumour cells. Small
      anaplastic tumour cells had very little GST staining. Where endothelial
      proliferation was evident, GST staining in endothelial cells was increased. Pi
      was always the predominant subclass, although GST alpha and mu were also
      expressed in some tumours. Cytochrome P450 reductase immunostaining was present
      in normal neurones and malignant astrocytes. Gemistocytic astrocytic tumour cells
      stained intensely. Further work is necessary to see if there is any correlation
      between immunostaining intensity survival or response to chemotherapy.

PMID- 8523086
TI  - The effects of dexamethasone on experimental brain tumors: I. Transcapillary
      transport and blood flow in RG-2 rat gliomas.
AB  - Dexamethasone dramatically improves cerebral edema associated with malignant
      gliomas. Although the pathophysiology of this effect is not clearly understood,
      many investigators have postulated that tumor capillary permeability is reduced
      by dexamethasone. We studied blood-to-tissue transport and blood flow in 178 RG-2
      transplanted gliomas in a control group and four groups given dexamethasone at
      doses of 3, 6, 9, and 12 mg/kg for four days. 14C-alpha aminoisobutyric acid
      (AIB) was used to study blood-to-tissue transport in 31 animals; in an additional
      27 animals 14C-AIB and 131I-iodoantipyrine (IAP) were used in double label
      experiments to study blood-to-tissue transport and blood flow. Regional
      measurements of the transfer constant (K) of AIB and blood flow (F) were made
      with quantitative autoradiography. There were significant differences between the
      control and dexamethasone-treated groups with regard to weight loss and plasma
      glucose. However, there was no significant effect of dexamethasone on values of K
      or F, regardless of the tumor or brain region examined, and regardless of the
      dose of dexamethasone administered. Analysis of the profiles of the transfer
      constant of AIB in the brain around tumor showed that the K of AIB decreased
      within 0.5 mm of the tumor edge in direct relationship to the dexamethasone dose.
      These results do not support the hypothesis that dexamethasone reduces brain
      tumor capillary permeability, and suggest that dexamethasone may decrease tumor
      associated cerebral edema by effects on bulk flow away from the tumor margin.

PMID- 8523087
TI  - The effects of dexamethasone on transcapillary transport in experimental brain
      tumors: II. Canine brain tumors.
AB  - We studied the effect of dexamethasone on transcapillary transport in ten Avian
      Sarcoma Virus (ASV)-induced canine brain tumors, before and one week after
      administration of dexamethasone, 2.5 mg/kg/day. A computed tomographic (CT)
      method was used to measure regional values of K1 (blood-to-tissue transfer
      constant), k2 (tissue-to-blood efflux constant), and Vp (tissue plasma vascular
      space) of meglumine iothalamate (Conray-60); the values were reconstructed for
      each 0.8 x 0.8 x 5 mm volume element of the CT data. For all tumors considered
      together, there was a decrease in the whole tumor K1 value of meglumine
      iothalamate from 26 +/- 2.2 (SE) before dexamethasone to 24 +/- 2.9
      microliters/g/min after dexamethasone. Vp decreased from 7.2 +/- 0.7 to 6.7 +/-
      0.9 ml/100 g, and the size of the tumor extracellular space (Ve) decreased from
      0.30 to 0.26 ml/g. These changes were not statistically significant. However,
      when each tumor was used as its own control, K1 significantly decreased after
      dexamethasone in four tumors, significantly increased in two and was unchanged in
      four. These results suggest that decreased blood-to-tissue transport may be one
      mechanism underlying resolution of tumor associated cerebral edema in some brain
      tumors and that the effects of dexamethasone on blood-to-tissue transport in
      brain tumors are variable from one tumor to the next. Decreased 'permeability'
      may not be the sole mechanism by which dexamethasone reduces tumor-associated
      cerebral edema.

PMID- 8523088
TI  - Response of brain tumors to chemotherapy, evaluated in a clinically relevant
      xenograft model.
AB  - Chemotherapy for brain tumors remains unsatisfactory. Despite increasing
      participation in clinical trials, there is a clear need for pre-clinical models.
      Heterotransplantation of surgical specimens directly into the anterior chamber of
      the nude mouse eye has been demonstrated to produce evaluable xenografts. Drug
      access in this model is considered to mimic the blood-brain barrier. Five
      clinical specimens in 3 children with primitive neuroectodermal
      tumor/medulloblastoma were the sources of 293 intraocular xenografts (5 cohorts
      by source). Each tumor-bearing mouse received 1 of 5 drugs or normal saline, by
      intraperitoneal injection, weekly for 5 weeks. Response was monitored for up to
      22 weeks, using a staging system which estimates the proportion of the anterior
      chamber filled by tumor. Results were analysed both as response rates (shrinkage
      in excess of 50%) at the conclusion of the treatment course and as time to tumor
      progression by the life table method. Comparison of response rates within cohorts
      by source of xenografts (exact chi-square test for overall and 2-sided Fisher's
      exact test for paired comparisons) indicated cyclophosphamide to be the most
      effective single agent. In logrank analyses cyclophosphamide achieved
      significantly longer delays to progression than all other drugs in one cohort and
      longer delays than all but diaziquone in 2 other cohorts. The intraocular
      xenograft model is a clinically relevant system for the study of therapeutic
      agents in brain tumors. The effectiveness of intensive dosage cyclophosphamide in
      a model dependent on access across the blood-aqueous barrier is important and
      consistent with recent clinical data.

PMID- 8523089
TI  - Ultrastructural neuropathologic effects of Taxol on neurons of the freshwater
      snail Lymnaea stagnalis.
AB  - Cerebral ganglia of the freshwater snail Lymnaea stagnalis were incubated in
      vitro in 10 microM Taxol for 8 and 24 h. Cremophor EL (0.1%) was used as a
      diluant. The tissue was processed for electron microscopy. Various
      ultrastructural parameters were assessed quantitatively. Cremophor EL appeared to
      seriously affect the cell somata of the multipeptidergic caudodorsal cells. In
      the Cremophor-controls the mean area of Golgi zones, the percentage dense
      material (neuropeptides) in these zones, the number of large electron dense
      granules (these are involved in neuropeptide processing) and the mean nuclear
      heterochromatin clump size, were significantly smaller than in the Ringer
      controls, whereas the number of lipid droplets was higher. All these parameters,
      except for the lipid droplets, were not different in the Cremophor-controls and
      the Taxol-treated specimens. After 24 h treatment, but not after 8 h, Cremophor
      EL furthermore induced an increase in the number of axonal microtubules. It is
      argued that the results might signify activation of the neurons by Cremophor EL.
      Taxol induced a significant increase in the number of microtubules in axons and
      cell somata. Furthermore an increase in the number of Golgi zones was observed,
      suggesting activated neuropeptide synthesis. In all groups immunostaining with
      antibodies to neuropeptides produced by the caudodorsal cells was normal. Release
      of neuropeptide (exocytosis) from axon endings was elevated after Taxol
      treatment, and exceptionally high in specimens cotreated with Taxol and Org 2766
      (incubation time 22 h). The effect of Org 2766 and Taxol on the number of
      microtubules was cumulative.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523090
TI  - Growth inhibition of human glioma cells modulated by retrovirus gene transfection
      with antisense IL-8.
AB  - The human glioma cell line, NP-1, expresses IL-8 mRNA and constitutively secretes
      IL-8 protein. Administration of recombinant IL-8 increased the proliferation of
      NP-1 cells in a dose-dependent manner. In the presence of anti-IL-8 antiserum,
      the IL-8 mediated proliferation of NP-1 cell growth was inhibited. Further, NP-1
      cell growth was inhibited by transfection of retroviral constructs encoding
      antisense IL-8 both in vitro and in vivo models. These results suggest that
      antisense IL-8 gene therapy could be beneficial in gliomas where autocrine
      stimulation by IL-8 is implicated.

PMID- 8523091
TI  - Occult systemic non-Hodgkin's lymphoma (NHL) in patients initially diagnosed as
      primary central nervous system lymphoma (PCNSL): how much staging is enough?
AB  - OBJECTIVE: To demonstrate the extent of staging necessary to exclude occult
      systemic stage IV NHL before making a diagnosis of stage I AE PCNSL. BACKGROUND:
      The diagnosis of PCNSL requires the demonstration of malignant lymphocytes within
      the CNS (usually by biopsy) and finding no evidence of systemic NHL. Different
      staging approaches have been recommended, ranging from extensive systemic
      evaluation (including bone marrow examination) to a more focused approach
      (abdominal and pelvic CT) to no systemic evaluation. We have employed a staging
      regimen that included: ophthalmologic evaluation (including slit lamp
      examination); CT of chest, abdomen, and pelvis; bilateral iliac crest aspirate
      and biopsy; flow cytometry of circulating lymphocytes; and, in men, testicular
      ultrasound. DESIGN/METHODS: We carried out a retrospective review of 128 patients
      entered into the Mayo Lymphoma Project data bank (1975-1994). RESULTS: Between
      the years 1975 and 1994, five patients (3.9%) were identified who fulfilled
      criteria for the diagnosis of PCNSL (typical clinical history, pathognomonic
      neuro-imaging, and histologic proof of NHL in brain tissue) but who had occult
      systemic NHL on staging (bone marrow 1, abdominal lymph nodes 3), or at autopsy
      (colon 1). Case histories are presented. CONCLUSIONS: Patients with apparent
      PCNSL may have systemic NHL. Complete staging is essential to the initial
      management of patients presenting as PCNSL to exclude systemic stage IV disease.

PMID- 8523092
TI  - Syncope as the initial presentation of nasopharyngeal carcinoma.
AB  - Syncope can be the first manifestation of nasopharyngeal carcinoma (NPC).
      Recently, we have encountered one such case and was able to eradiate this symptom
      by combined chemotherapy and radiotherapy.

PMID- 8523093
TI  - A phase II study of every other day high-dose ifosfamide in pediatric brain
      tumors: a Pediatric Oncology Group Study.
AB  - Despite reported activity in many other solid tumors, high-dose ifosfamide
      produces few objective responses in recurrent pediatric brain tumors. Alkylating
      agents such as cyclophosphamide (CYCLO) possess good activity in many of solid
      tumors, including brain tumors. Although Ifosfamide (IFOS), a structural congener
      of CYCLO, has been suggested to have greater activity in several tumors, its
      activity in brain tumors is uncertain. We conducted a phase II trial of every
      other day IFOS (3 gm/M2/qod x 3) in 87 recurrent pediatric brain tumors.
      Responses were evaluable in 71 patients. Partial responses occurred in 1/6
      patients with low grade astrocytoma, 1/16 with malignant glioma, 1/16 with
      medulloblastoma, 1/3 with pineoblastoma and 1/12 patients with ependymoma. No
      responses occurred among 10 patients with brain stem gliomas or 8 patients with
      other brain tumors. Despite the poor objective response rate, 23/71 patients were
      clinically and imaging stable for periods of 8-62 weeks. There was no
      relationship between prior CYCLO treatment and subsequent response or failure
      with IFOS. The predominant toxicity was myelosuppression. Although generally
      reversible, prolonged suppression and sepsis were responsible for the deaths of 3
      heavily pretreated patients. Renal toxicity was uncommon; 2 patients had grade
      III, and one grade IV renal tubular dysfunction. One patient had grade IV
      hematuria. Neurotoxicity was less common than in studies of daily ifosfamide;
      only 1 patient had grade IV neurotoxicity. Three patients had grade III or IV
      IFOS related hyponatremia. Despite the good stable disease rate, the poor rate of
      objective response suggests that IFOS monotherapy possesses little clinically
      meaningful activity in brain tumors.

PMID- 8523094
TI  - Meta-[131I]iodobenzylguanidine uptake and meta-[211At]astatobenzylguanidine
      treatment in human medulloblastoma cell lines.
AB  - Uptake of radioiodinated meta-iodobenzylguanidine (MIBG) has been demonstrated in
      the neural crest tumors, including neuroblastoma, pheochromocytoma, and carcinoid
      tumors, and is presently in use diagnostically and therapeutically in these
      settings. Cells comprising medulloblastoma, the most common central nervous
      system malignancy in childhood, may be derived from a common germinal
      neuroepithelial cell as neural crest tissue, and as a result, also may have the
      capacity for accumulating MIBG. To investigate this hypothesis, we measured the
      in vitro binding of [131I]MIBG to 9 medulloblastoma-derived cell lines and the SK
      N-SH neuroblastoma line known to accumulate MIBG. Seven of the medulloblastoma
      lines exhibited MIBG binding. The cell line with the greatest uptake, D384 Med,
      bound 11.2 +/- 0.9% of added [131I]MIBG activity compared with 47.1 +/- 2.3% for
      the SK-N-SH cell line. When 2 of the cell lines, D384 Med and D458 Med, were
      treated with the alpha-particle emitting analogue meta
      [211At]astatobenzylguanidine ([211At]MABG), as much as a 3-log cell kill was
      observed in limiting dilution clonogenic assays. Exposure to considerably higher
      activity levels of [211At]astatide was required to achieve a similar degree of
      cell kill, suggesting that this cytotoxicity was not related to nonspecific
      effects of alpha-particle irradiation. We conclude that the uptake capacity of
      medulloblastoma cell lines for [131I]MIBG uptake in vitro, while lower than that
      seen in SK-N-SH neuroblastoma cells, is sufficient to permit [211At]MABG to be
      used with significant therapeutic effectiveness.

PMID- 8523095
TI  - Hormesis: fact or fiction?

PMID- 8523096
TI  - Delayed data acquisition for optimal PET activation studies with oxygen-15-water
      in cerebral arteriovenous malformation.
AB  - In the clinical application of activation PET studies with 15O-water, optimal PET
      images are required when the high activity of a nearby lesion might affect the
      activated area. METHODS: To determine the optimal time for data acquisition of
      PET images, we performed serial dynamic PET measurements in five patients with
      cerebral arteriovenous malformation (AVM). All AVMs were closest to the motor
      cortices, and the activation task was opponent finger movement contralateral to
      the AVM. Activation PET and MR images were coregisterated for localization of
      activated foci. RESULTS: Time-activity curves of the nidus and normal cortex from
      the dynamic PET data demonstrated a discrepancy in peak time and significant
      radioactivity increase in the nidus during the early phase. Elimination of the
      initial PET data provided better contrast in activated foci without affecting the
      calculated cerebral blood flow of other areas. CONCLUSION: Delayed data
      acquisition can avoid interference of the AVM nidus with the activated area.

PMID- 8523097
TI  - Evaluation of cerebral infarction with iodine 123-iomazenil SPECT.
AB  - This study evaluates ischemic damage to central benzodiazepine (BZD) receptor
      binding in the brain with [123]iomazenil SPECT in relation to CT hypodense
      lesions and blood flow abnormalities. METHODS: Nine patients with middle cerebral
      artery territory infarction were studied. Iomazenil images obtained 180 min
      postinjection were analyzed for BZD receptor binding. The cortical infraction,
      visualized as CT hypodense area on CT, the peri-infarct area, visualized as
      normodensity surrounding the infarction on CT, the intrahemispheric remote area
      and the cerebellum were analyzed by taking the ratio of the lesion to
      contralateral mirror region (L/C ratio). CT during the chronic stage and
      perfusion images obtained during the smallest time difference between the two
      studies were used for comparative analysis. RESULTS: The mean L/C ratio of
      iomazenil uptake was 0.53 +/_ 0.08, 0.79 +/- 0.07, 0.98 +/- 0.03 and 1.00 +/-
      0.04 in the infarct, peri-infarct and remote areas and the cerebellum,
      respectively. The infarct and peri-infarct areas showed significant decrease
      compared with unity. The corresponding mean L/C ratio for blood flow was 0.52 +/-
      0.08, 0.73 +/- 0.07, 0.83 +/- 0.09, and 0.80 +/- 0.07, respectively. In all
      areas, the ratios were significantly decreased compared with unity. There was
      significant difference between the L/C ratio for blood flow and iomazenil in the
      remote area and the cerebellum. CONCLUSION: Iodine-123-iomazenil SPECT imaging
      may provide new information on ischemic damage to the brain, particularly
      neurons.

PMID- 8523098
TI  - A new PET ligand for the dopamine transporter: studies in the human brain.
AB  - Carbon-11-d-threo-methylphenidate, the active enantiomer of methylphenidate
      (ritalin), has been shown to bind uniquely to the dopamine transporter in the
      baboon brain. This study characterizes its binding in the human brain and
      measures its test-retest reproducibility. METHODS: Studies were done in seven
      normal controls, each of whom was scanned with [11C]d-threomethylphenidate on two
      different occasions. Six subjects were scanned twice 3-5 wk apart without
      intervention to assess reproducibility. One subject was scanned sequentially
      before and after treatment with methylphenidate to assess binding saturability.
      Graphical analysis was used to obtain tissue distribution volumes (DV). The ratio
      of the DV in the basal ganglia (BG) to that in cerebellum (CB) (DVBG/DVCB), which
      corresponds to (Bmax/Kd) + 1 was used to estimate dopamine transporter
      availability. RESULTS: Highest tracer uptake occurred in the basal ganglia, where
      activity peaked 7-11 min postinjection. The half-clearance time for the tracer in
      brain regions other than the basal ganglia was 74 min. In the basal ganglia, only
      10%-15% of the activity had cleared at 74 min. Time-activity curves for [11C]d
      threo-methylphenidate in the basal ganglia and cerebellum were highly
      reproducible. The average percent change for the absolute value for DVBG/DVCB was
      6.5% +/- 4% (range 0-12%). Methylphenidate pretreatment decreased basal ganglia
      uptake but not cortical or cerebellar binding and reduced DVBG/DVCB by 62% and
      Bmax/Kd by 91%. CONCLUSION: These studies demonstrate that [11C]d-threo
      methylphenidate binding in the human brain is reversible, highly reproducible and
      saturable. Thus, it is an appropriate PET ligand to measure dopamine transporter
      availability.

PMID- 8523099
TI  - Functional brain imaging in HIV-1-infected children born to seropositive mothers.
AB  - The aim of this work was to study cerebral function in vertically infected
      children with human immunodeficiency virus 1 (HIV-1). METHODS: PET with 18F
      labeled fluorodeoxyglucose (FDG) was performed in eight children (2.5-5.5 yr):
      three with severe neurological symptoms and five without. Quantitative analysis
      was based on gray matter cortical and subcortical regions of interest for which
      glucose utilization was measured. RESULTS: Diffuse hypometabolism and subcortical
      hypermetabolism were found in the three children with severe neurological signs;
      the five other children had temporo-occipital cortical hypometabolism, mainly on
      the right side. CONCLUSION: Functional cerebral abnormalities seem to precede
      clinical symptoms in HIV-1infection of the brain in children.

PMID- 8523100
TI  - Carbon-11-methionine PET evaluation of intracerebral hematoma: distinguishing
      neoplastic from non-neoplastic hematoma.
AB  - We evaluated whether PET with L-methyl-11C-methionine (11C-methionine) was
      clinically useful in distinguishing neoplastic from non-neoplastic intracerebral
      hematoma. METHODS: We examined eight patients with neoplastic (n = 4) or non
      neoplastic (n = 4) intracerebral hematomas between 5 and 68 days after the
      bleeding episode using PET with 11C-methionine (Met-PET). RESULTS: Carbon-11
      methionine accumulated in the area surrounding the hematoma in both groups,
      except in one patient with an acute hypertensive hematoma. Between 22 and 45 days
      after the ictus, non-neoplastic hematomas showed increased 11C-methionine
      accumulation largely in accordance with the contrast-enhanced areas on CT or MR
      images; whereas between 14 and 68 days after bleeding, neoplastic hematomas
      showed increased 11C-methionine accumulation that extended beyond the contrast
      enhanced areas on CT or MR images. The intensity of 11C-methionine accumulation
      in tumor tissue was greater than that in non-neoplastic hematomas. CONCLUSION:
      Preliminary results suggest that Met-PET can distinguish neoplastic from non
      neoplastic hematomas on the basis of differences in lesion extent compared with
      CT or MR findings.

PMID- 8523101
TI  - Super-early iodine-123-iodoamphetamine SPECT imaging of human primary motor
      cortex.
AB  - This study was designed to visualize the motor function area related to finger
      movements in normal human brain using super-early (first 640 sec of acquisition)
      [123l]iodoamphetamine ([123I]IMP) SPECT. METHODS: Seven healthy male volunteers
      performed paired, isolated baseline and task sessions. The task was a right thumb
      to-fingers opposition task, which was loaded for the initial 11 min of the
      session. A high-performance, four-head SPECT camera was used. At each session,
      administration of 222 MBq [123I]IMP was followed by 16 serial 160-sec dynamic
      SPECT acquisitions. To obtain matched brain anatomical images, MRI was also
      performed using the same slice formation as in the SPECT study. After image
      reconstruction, ROIs were set on bilateral sensorimotor hand areas (SMHA), the
      supplementary motor area (SMA), the frontal, temporal and occipital lobes and the
      cerebellar hemispheres. The percent increase of ROI activity (%INC) in the task
      session compared with that in the baseline session was calculated in each ROI
      after normalization to the global brain radioactivity. RESULTS: There was
      significant activation of the left SMHA by the task, the amplitude of which was
      maximal in the initial phase of dynamic images (the super-early phase). This area
      was located in the left peri-central area identified on the analogous slice in
      the MR image. The left SMHA showed gradual and statistically significant decrease
      of %INC during the three phases. CONCLUSION: Super-early [123I]IMP may be used to
      identify the primary motor cortex and to evaluate its function in some
      pathological conditions.

PMID- 8523102
TI  - Technetium-99m-sestamibi imaging before reoperation for primary
      hyperparathyroidism.
AB  - Recent studies have reported high sensitivities for parathyroid localization with
      99mTc-sestamibi and have been performed using either 123I/99mTc-sestamibi or a
      double-phase sestamibi scanning technique. These studies have focused primarily
      on patients undergoing initial surgery. We studied 35 patients prior to
      reoperative surgery to investigate the relative sensitivities of these two
      technique sin this patient population. METHODS: Double-phase sestamibi scanning
      (early and delayed imaging) was performed in all patients. Evaluable 123I/99mTc
      sestamibi subtraction studies were also obtained in 25 patients. Results were
      correlated with surgical findings in 32 patients and with clinical outcome in 3
      patients in whom mediastinal lesions were radiographically ablated. RESULTS:
      Overall, double-phase sestamibi imaging detected 23 of 39 abnormal parathyroid
      glands (59%), whereas 123I/99mTc-sestamibi detected 19 of 27 (70%). Oblique
      imaging, delayed imaging and 123I subtraction all contributed to sensitivity, and
      123I subtraction also proved useful in patients with partial thyroid suppression.
      Two patients had lesions visible on the early sestamibi images that were not seen
      at all on the delayed scans. There were four false-positive findings. CONCLUSION:
      No significant differences between double-phase sestamibi and 123I/99mTc
      sestamibi subtraction scanning were found, although the latter tended to be more
      sensitive.

PMID- 8523103
TI  - Interpretation of captopril renography by nuclear medicine physicians.
AB  - This study was designed to assess intra- and interobserver variability and
      diagnostic accuracy of nuclear medicine physicians in their evaluation of
      baseline and captopril renograms. METHODS: The diagnostic performance of three
      experienced nuclear medicine physicians according to their interpretation of
      baseline, captopril and paired renograms was assessed. To this end, the readers
      evaluated the renograms of 28 hypertensive patients in whom a diagnosis of
      renovascular hypertension was suspected on the basis of clinical clues. All
      patients also underwent angiography. The readers were unaware of the angiographic
      diagnosis. RESULTS: Thirteen of 28 patients proved to have renal artery stenosis
      (8 unilateral, 5 bilateral) on renal angiography. The concordance in the
      renographic diagnoses between the three readers was reasonably good, with an
      intraobserver agreement and kappa (observed agreement corrected for chance)
      ranging from 64% to 89% and from 0.52 to 0.75, respectively, and an interobserver
      agreement and kappa ranging from 68% to 86% and from 0.61 to 0.82. The
      sensitivity of their interpretation of paired baseline plus captopril renograms
      in relation to the angiographic diagnosis is poor and below 50%. The post-test
      probability of RAS in case of a negative renographic study was found to be rather
      similar to the pre-test probability (prevalence) of 46%. Blinding readers to
      which renogram was obtained after captopril imaging increased their accuracy.
      CONCLUSION: The intra- and interobserver agreement between experienced nuclear
      medicine physicians who evaluate renograms was found to be reasonably good.
      Blinding readers as to which renogram is the pre- and post-captopril image seems
      to enhance their diagnostic accuracy in instances of positive scans.

PMID- 8523104
TI  - Metabolic imaging of ovarian tumors with carbon-11-methionine: a PET study.
AB  - This study examines the potential of 11C-methionine as a PET tracer in metabolic
      imaging of benign and malignant ovarian tumors. METHODS: Four patients with one
      or two benign ovarian tumors (endometriomas or cystadenomas), two patients with a
      tumor of borderline malignancy and seven patients with ovarian cancer were
      studied with 11C-methionine and PET before laparotomy. CT or MRI were performed
      as a reference. Tracer uptake was quantitated by calculating tracer standardized
      uptake values (SUVs) and the kinetic influx constants (Ki values). RESULTS:
      Benign or borderline malignant tumors did not accumulate 11C-methionine, whereas
      all carcinomas had significant uptake. The mean SUV of the primary carcinomas was
      7.0 (s.d., 2.2) and the mean Ki was 0.14 min-1 (s.d., 0.1 min-1), but the
      distribution of tracer uptake was highly heterogenous in four of six tumors.
      CONCLUSION: Ovarian cancer can be imaged with 11C-methionine and PET. This method
      also may be of value in the differential diagnosis between benign and malignant
      ovarian neoplasms. Due to physiological accumulations and methodological
      limitations, the value of 11C-methionine PET in the staging of ovarian cancer
      appears to be limited.

PMID- 8523105
TI  - Thallium-201 in brain tumors: relationship between tumor cell activity in
      astrocytic tumor and proliferating cell nuclear antigen.
AB  - This study was performed to assess the relationship between 201Tl chloride uptake
      and brain tumor proliferation using monoclonal antibody Ki-67 and proliferating
      cell nuclear antigen (PCNA). METHODS: Thirty-four patients with brain tumors were
      studied. Serial SPECT images were recorded and thallium uptake (Tl index) and
      washout rates in the tumors were calculated. Imaging results were compared with
      those from biopsy and histology. Cell proliferation was determined by PCNA or Ki
      67 monoclonal antibody staining. RESULTS: Thallium-201-chloride indices of the
      astrocytoma were 1.73 +/- 0.17 and 1.48 +/- 0.07 on early and delayed images,
      respectively. On the other hand, 201TI indices for anaplastic astrocytoma were
      2.60 +/- 1.05 and 1.76 +/- 0.93 and 3.26 +/- 1.63 and 2.23 +/- 0.56 for
      glioblastoma. The correlation between the 201TI (delay) and Ki-67 indices for
      astrocytic tumor. There were no significant differences between Ki-67/PCNA
      indices and washout rates. CONCLUSION: There was a positive correlation between
      PCNA but not the Ki-67 labeling index and the 201Tl index. With the use of a
      noninvasive technique, 201TI index supports the PCNA index.

PMID- 8523106
TI  - PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's
      disease.
AB  - Animal and human autoradiographic studies have shown increased in vitro binding
      of the peripheral benzodiazepine binding site antagonist PK 11195 in areas of
      microgliosis, including the temporal association cortex of patients with
      Alzheimer's disease. To further elucidate the role of cellular inflammation and
      microgliosis in Alzheimer's disease during life, we used PET and [11C]PK 11195, a
      peripheral benzodiazepine receptor ligand known to bind avidly to microglia.
      METHODS: Eight patients with a diagnosis of probable Alzheimer's disease
      underwent PET of the brain using [11C]PK 11195 and, for comparison, with [18F]FDG
      to determine cerebral glucose metabolism. Uptake of [11C]PK 11195 in various
      brain regions was expressed relative to that in the cerebellum and compared to
      values determined in one normal elderly subject and in clinically and
      anatomically unaffected hemispheres of seven patients with small unilateral
      gliomas. RESULTS: No increases in peripheral benzodiazepine binding were
      identified in patients with probable Alzheimer's disease, and binding was lowest
      in regions that were most hypometabolic. CONCLUSION: The peripheral
      benzodiazepine binding sites associated with microgliosis and cellular
      inflammation in Alzheimer's disease at postmortem are undetectable by PET using
      [11C]PK 11195 in patients with mild-to-moderate dementia.

PMID- 8523107
TI  - Abnormal gallium-67 skull uptake: a sign of peripheral marrow activation in HIV
      positive patients with disseminated mycobacterioses.
AB  - The purpose of this study was to investigate the significance of abnormal 67Ga
      citrate skull uptake in AIDS patients with mycobacterioses. METHODS: Gallium-67
      scans of 39 HIV-positive patients who have been diagnosed with mycobacterioses
      were analyzed; the scans of 15 consecutive HIV-positive patients without
      mycobacterioses were also reviewed as a control group. The skull was chosen to
      assess bone marrow uptake because of the absence of overlapping structures.
      RESULTS: Twenty-nine of 39 (74%) patients with mycobacterial infections had
      disseminated disease. Gallium-67 uptake in the skull was visualized in 24 of
      these 29 patients (82%). One of the patients without disseminated disease and one
      patient in the control group (n = 15) showed skull uptake. CONCLUSION: Abnormal
      67Ga skull uptake appears to be a sensitive (82%) and specific (82%) indicator of
      disseminated mycobacterial infection in HIV-positive patients.

PMID- 8523108
TI  - Utility of technetium-99m-MAG3 diuretic renography in the neonatal period.
AB  - Diuretic renography performed in the neonatal period has been reported to be
      unreliable in diagnosing obstruction. METHODS: The scans of 27 neonates (age up
      to 28 days; mean 17 days) with a total of 53 renal units were reviewed; a renal
      unit being defined as comprising a kidney and its ureter. All were referred
      following perinatal ultrasound diagnosis of hydronephrosis or
      hydroureteronephrosis. The neonates had standard diuretic renography using MAG3
      with a frusemide dose of 1 mg/kg followed by another image obtained after gravity
      assisted drainage. RESULTS: There were 17 normal undilated renal units showing
      excellent diuretic responses with clearance half-times of 0.6-7.7 min. Eighteen
      renal units were diagnosed as having pelvi-ureteric junction (PUJ) obstruction,
      with surgical confirmation in all. Eight were diagnosed as unobstructed and of
      these seven were confirmed nonobstructed by serial imaging using ultrasound and
      MAG3, but one subsequently had pyeloplasty performed for PUJ obstruction. One
      unit was indeterminate for PUJ obstruction but had good clearance with gravity
      assisted drainage and was shown to be unobstructed on repeat studies. Of nine
      units diagnosed as having vesico-ureteric junction (VUJ) obstruction, eight had
      surgical confirmation and one remains of uncertain final diagnosis. Co-existing
      VUJ obstruction could not be diagnosed in two units with PUJ obstruction because
      of insufficient radiotracer drainage through the tight stenosis into the ureter.
      CONCLUSION: An adequate diuretic response is present in the neonatal period using
      MAG3 and this allows for reliable diagnosis of obstruction. An unobstructed or
      indeterminate result necessitates follow-up imaging to ensure obstruction does
      not develop. Co-existing VUJ obstruction may be missed in a scan showing PUJ
      obstruction.

PMID- 8523109
TI  - Relationships between gastric emptying, intragastric meal distribution and blood
      glucose concentrations in diabetes mellitus.
AB  - The aim of this study was to evaluate the prevalence of disordered intragastric
      meal distribution and the relationships between gastric emptying, intragastric
      distribution, glycemic control and gastrointestinal symptoms in diabetes
      mellitus. METHODS: Eighty-six patients with diabetes mellitus had measurements of
      gastric emptying and intragastric distribution of a radioisotopically labeled
      solid/liquid meal (100 g beef and 150 ml 10% dextrose), glycemic control (plasma
      glucose concentrations), upper gastrointestinal symptoms (questionnaire) and
      autonomic nerve function (cardiovascular reflexes). Results were compared to
      those obtained in 20 normal volunteers. RESULTS: Solid and liquid gastric
      emptying were delayed in the diabetic patients and correlated weakly.
      Intragastric meal distribution was also often abnormal, with increased retention
      of both solid and liquid in the proximal stomach and increased retention of solid
      but not liquid in the distal stomach. In all patients with increased retention of
      solid in the proximal stomach, emptying from the total stomach was delayed.
      Gastric emptying of liquid was slower in those subjects who had a mean plasma
      glucose > 15 mmol/liter during the gastric emptying measurement, when compared to
      the remainder of the group. CONCLUSION: In patients with diabetes mellitus, there
      is poor relationship between solid and liquid gastric emptying and intragastric
      meal distribution is frequently abnormal. Interpretation of the results of
      gastric emptying measurements should consider meal composition and plasma glucose
      concentrations.

PMID- 8523110
TI  - Initial clinical evaluation of iodine-125-labeled chimeric 17-1A for metastatic
      colon cancer.
AB  - The internalizing properties of murine antibody 17-1A in human colon cancer cells
      make it attractive as a carrier for radionuclides with short range emissions such
      as 125I. Murine 17-1A IgG2a antibody, which reacts against human gastrointestinal
      cancers, has been chimerized by joining its variable region with human IgG1 k
      constant region. A pilot clinical trial of increasing doses of 125I-chimeric 17
      1A in patients with metastatic colorectal cancer has been conducted. METHODS:
      Patients were treated in groups of 2-4; 2 patients at Hahnemann University and 26
      at the University of Alabama at Birmingham. Groups 1-5 received single
      administrations with 125I doses of 20, 40, 60, 80 or 100 mCi. Subsequent groups
      received therapeutic doses of 150, 200 or 250 mCi, with the dose subdivided into
      infusing of 50 or 100 mCi at 4-day intervals. All treatments were delivered in an
      outpatient setting using radiation precautions. Labeling at 10 mCi/mg antibody
      was performed on the day of treatment. RESULTS: Pharmocokinetics of circulating
      antibody was studied for initial patients, showing alpha T 1/2 of 17-27 hr and
      beta T 1/2 of 100-190 hr. Whole-body T 1/2 of radioactivity was determined by
      measuring urinary excretion or gamma emissions. Treatment was well tolerated
      without significant acute or late side effects. No significant bone marrow
      suppression or other dose-limiting toxicities were noted over this dose range. No
      objective responses were noted. CONCLUSION: These results show that high-dose
      outpatient radioimmunotherapy with an 125I-labeled internalizing antibody can be
      achieved without significant patient toxicity or radiation hazard.

PMID- 8523111
TI  - Drug therapy and cerebral perfusion in obsessive-compulsive disorder.
AB  - Cerebral perfusion in a previously untreated patient with obsessive-compulsive
      disorder was studied qualitatively and semi-quantitatively with SPECT before, and
      during and 6 wk after treatment with clomipramine. The patient's symptoms
      disappeared while on medication and relapsed after drug withdrawal. At baseline,
      there was an increased perfusion ratio in the bilateral orbitofrontal, anterior
      cingular, frontotemporal and right caudate regions. These alterations disappeared
      during drug therapy. After treatment discontinuation and symptomatic relapse, the
      same pattern of hyperactivity was found. Semiquantitative measurements after
      treatment withdrawal showed a return to perfusion values similar to those
      observed before treatment in subcortical structures. In cortical areas, this
      level was not completely achieved. Subtraction SPECT images showed perfusion
      changes at the orbitofrontal, caudate and thalamic levels.

PMID- 8523112
TI  - Thallium-201 accumulation in myositis ossificans and in juxta-articular
      ossification.
AB  - We present the findings on 201Tl and 99mTc-MDP scintigraphy in three patients
      suffering from heterotopic ossification (two patients presenting with myositis
      ossificans and one patient presenting with juxta-articular ossification in
      combination with myositis ossificans). Since resection of the lesions has to be
      delayed until stabilization, 99mTc-MDP is often used as a parameter of lesional
      activity, although it is not optimal. For this clinical problem, we evaluated
      201Tl scintigraphy as a marker of metabolic activity. In addition to the well
      documented uptake of 99mTc-MDP, marked accumulation of 201Tl was observed in all
      heterotopic ossification sites. Hence, our results support the use of 201Tl
      scintigraphy in the therapeutic management and monitoring of conditions
      associated with ectopic ossification. On the other hand, although myositis
      ossificans is sometimes clinically, radiographically and even histologically
      confused with extraosseous osteogenic sarcoma, 201Tl accumulation may not be a
      helpful factor in the differential diagnosis due to the presence of tracer
      accumulation in both disorders.

PMID- 8523113
TI  - Presurgical diagnosis of a primary carcinoid tumor of the thymus with MIBG.
AB  - A primary carcinoid tumor of the thymus showing ectopic ACTH syndrome was
      evaluated scintigraphically with four radiopharmaceuticals and a fluorescence
      method. Iodine-123-MIBG and 201Tl-Cl scintigraphy clearly demonstrated the tumor.
      Gallium-67-citrate and 99mTc(V)-DMSA showed no tumor uptake. The fluorescence
      method confirmed numerous storage granules of norepinephrine. Iodine-123-MIBG
      scintigraphy could be useful in the presurgical diagnosis of carcinoid tumors of
      the thymus.

PMID- 8523114
TI  - Enhanced bone metabolism induced by acupuncture.
AB  - A 29-yr-old man with several years of back pain was referred for a bone scan.
      High-resolution regional spot images of the skeleton were obtained following
      intravenous injection of 20 mCi 99mTc-methylene diphosphonate. Posterior and
      lateral images of the skull showed focal increased uptake in several regions of
      the skull. Upon questioning, the patient stated that he had received acupuncture
      treatment for his back pain several times in the same regions as the increased
      uptake. The needle placement was confirmed by the patient's acupuncturist.
      Acupuncture can cause enhanced bone metabolism demonstrated by increased activity
      on bone scans.

PMID- 8523115
TI  - Technetium-99m-tetrofosmin imaging of differentiated mixed thyroid cancer.
AB  - This report describes the accurate localization of metastatic lesions in a
      patient with differentiated mixed thyroid cancer using 99mTc-tetrofosmin imaging.
      A 66-yr-old women with a cytological diagnosis of follicular thyroid cancer
      associated with a large amount of goiter changes was studied by 99mTc-tetrofosmin
      total-body scintigraphy. No significant tetrofosmin uptake was observed in the
      thyroid nodules, which mainly showed goiter abnormalities. Abnormal increased
      tetrofosmin uptake, however, was found in metastatic tumor lesions located in the
      cervical and dorsal spine as well as in the left lower chest wall and lungs. In
      conclusion, 99mTc-tetrofosmin, a new radiopharmaceutical proposed for myocardial
      perfusion imaging, may be useful in patients with thyroid cancer.

PMID- 8523116
TI  - In vivo imaging of the brain vesicular monoamine transporter.
AB  - In the search for an in vivo marker of monoamine nerve terminal integrity, we
      investigated methoxytetrabenazine (MTBZ) as a tracer of the brain synaptic
      vesicular monoamine transporter (VMAT2). METHODS: The biodistribution, metabolism
      and in vivo specificity of MTBZ binding were first evaluated in rodents and the
      human dosimetry was estimated. Subsequently, the human brain distribution of
      VMAT2 binding was determined in normal volunteers following administration of
      [11C]MTBZ. Brain regional time-activity curves were obtained, and parametric
      transport and binding images were calculated using arterial blood sampling and a
      two-compartment tracer kinetic model. RESULTS: Regional rat brain localization of
      [3H]MTBZ 15 min postinjection was consistent with the known monoamine nerve
      terminal density, which demonstrated the highest activity in the striatum,
      lateral septum, substantia nigra pars compacta, the raphe nuclei and the locus
      coeruleus. At this time, chromatography revealed over 82% of brain activity, but
      less than 47% of plasma activity corresponded to authentic MTBZ. In vivo
      [11C]MTBZ binding in the mouse brain was inhibited by coinjection of excess
      unlabeled dihydrotetrabenazine. In humans [11C]MTBZ had high initial brain uptake
      and rapid clearance from all regions, with longest retention in areas of high
      VMAT2 concentration. Parametric quantification of VMAT2 density revealed the
      highest distribution volume in the putamen and caudate with lower values in
      cerebral cortex and cerebellum. CONCLUSION: Carbon-11-MTBZ is a suitable ligand
      for PET quantification of the vesicular monoamine transporter in the human brain.

PMID- 8523117
TI  - Incorporation of [1-carbon-11]palmitate in monkey brain using PET.
AB  - We determined regional incorporation coefficients (k*) of plasma [1-11C]palmitate
      into stable brain lipids of anesthetized monkeys with PET. METHODS: Carbon-11
      palmitate was injected intravenously in untreated animals and in animals
      pretreated with methyl palmoxirate (MEP), an inhibitor of beta-oxidation of
      palmitate in the brain and periphery. Plasma radioactivity was followed, and
      brain radioactivity was determined at various times using PET. A least-squares
      method was used to fit the data to an operational equation to obtain regional
      values of k* and of cerebral blood volume (Vb) in individual experiments.
      RESULTS: MEP significantly decreased the integral of plasma [11C]CO2 following
      11C-palmitate infusion. Mean values of k* in monkeys not given MEP were 4.9, 4.2,
      4.9, 4.0 and 2.9 x 10(-5) ml/sec.g for the temporal, frontal, parietal and
      occipital cortices and white matter, respectively. With the exception of k* in
      white matter, which was increased by MEP, k* in the other brain regions was not
      significantly changed by MEP. The Vb ranged from 0.035 ml/g to 0.048 ml/g in gray
      matter regions and equaled 0.022 ml/g in white matter. CONCLUSION: PET can be
      used to determine regional incorporation coefficients of 11C-palmitate into the
      primate brain in vivo. Combined with MEP, 11C-palmitate could be used with PET to
      examine regional brain phospholipid metabolism in humans in normal and
      pathological conditions.

PMID- 8523118
TI  - Rat adjuvant arthritis: imaging with technetium-99m-anti-CD4 Fab' fragments.
AB  - The abundance of CD4 molecules on inflammatory cells in the synovial membrane
      renders anti-CD4 monoclonal antibodies (MAbs) or their fragments very promising
      for specific imaging of arthritic joints. METHODS: Joint uptake and body
      distribution of a 99mTc-labeled Fab', derived from the anti-rat CD4 MAb W3/25
      (IgG1), were investigated following intravenous injection in normal and adjuvant
      arthritic rats. An isotype-matched Fab' (anti-human nonspecific crossreacting
      antigen-90) was used as control. RESULTS: A 14-hr sequential pinhole scan of the
      ankle joints revealed that both the anti-CD4 and the control Fab' accumulated to
      a higher degree in arthritic than in normal ankle joints; however, accumulation
      of the anti-CD4 Fab' in arthritic joints exceeded that of the control Fab'
      (approximate to 1.6 fold). Preferential joint accumulation of anti-CD4 Fab' was
      confirmed by whole-body scans at 14 hr and by direct well counter measurements of
      tissue samples at 16 hr following injection. Unlike the control Fab', the anti
      CD4 Fab' preferentially accumulated in the liver and lymph nodes, organs rich in
      CD4-positive cells, as observed by direct tissue measurements. CONCLUSION:
      Despite its monovalency, the anti-CD4 Fab' retains the in vivo selectivity for
      CD4-positive cell-rich tissues, previously reported for the complete anti-CD4
      MAb, and improves imaging of inflamed joints in experimental adjuvant arthritis.

PMID- 8523119
TI  - Enhanced tumor specificity of 741F8-1 (sFv')2, an anti-c-erbB-2 single-chain Fv
      dimer, mediated by stable radioiodine conjugation.
AB  - The goal of this study was to determine if the stabilization of the radioiodine
      protein bond by the N-succinimidyl p-iodobenzoate (PIB) method improved the
      degree and specificity of tumor localization of 125I-741F8-1 (sFv')2, an anti-c
      erbB-2 sFv dimer, in an immunodeficient murine model. METHODS: Gamma camera
      images were acquired 21 hr after intravenous administration of 131I-741F8-1
      (sFv')2 labeled by the p-iodobenzoate or chloramine T methods. The stability of
      the radioiodine-protein bond also was assessed in plasma samples after
      intravenous injection of 125I-741F8-1 (sFv')2 labeled by either the chloramine T
      or p-iodobenzoate methods. RESULTS: By 6 hr postinjection, 97% of the activity
      associated with the 125I-741F8-1 (sFv')2 labeled by the p-iodobenzoate method was
      protein bound compared with 61% after labeling with the chloramine-T method.
      These observations indicate that increasing the stability of the conjugation
      between the radioiodine and the sFv molecule can significantly increase the
      degree and specificity of tumor targeting. Significantly greater tumor retention
      (p < 0.005) and lower blood (p < 0.001), spleen (p < 0.001) and stomach (p <
      0.005) retention were observed in biodistribution studies when the p-iodobenzoate
      conjugate was used. This resulted in superior tumor-to-organ ratios for all
      tissue samples studied. CONCLUSION: These observations may have clinical
      relevance for the use of radiolabeled sFv as imaging agents.

PMID- 8523120
TI  - Ultra-high resolution SPECT system using four pinhole collimators for small
      animal studies.
AB  - We describe a newly developed ultra-high resolution SPECT system using four
      pinhole collimators for small animal studies. METHODS: The system utilizes a
      clinical four-head SPECT scanner with specially designed pinhole collimators.
      Four types of pinholes with different configurations were designed with different
      effective aperture sizes (1.0, 2.0 and 4.0 mm) and rotating radii (40 mm and 50
      mm). The distance from the axis of rotation to the scintillator was fixed to 180
      mm. A filtered backprojection algorithm was used to reconstruct SPECT images
      after fanbeam-to-parallel-beam data conversion. RESULTS: The system provided a
      reconstructed spatial resolution of 1.65 mm (FWHM) and sensitivity of 4.3
      kcps/microCi/ml with the best type of pinholes, respectively. The 99mTc-HMPAO
      SPECT image in rat studies clearly visualized small brain structures, and the
      left ventricular myocardium and cardiac cavity were clearly separated with 99mTc
      MIBI. Dynamic SPECT imaging of rat brain with [123I]iomazenil was also feasible.
      CONCLUSION: This ultra-high resolution SPECT system can be used to measure the
      regional distribution of radiolabeled tracers in small animals in vivo and may
      play a significant role in the development of new radiopharmaceuticals and in
      studies of various disease models using living animals.

PMID- 8523121
TI  - Pinhole SPECT: ultra-high resolution imaging for small animal studies.

PMID- 8523122
TI  - Striatal dopamine transporter imaging in nonhuman primates with iodine-123-IPT
      SPECT.
AB  - The regional distribution, kinetics and pharmacological specificity of a new
      radioiodinated cocaine analog, N-((E)-3-iodopropen-2-yl)-2 beta-carbomethoxy-3
      beta-(4-chlorophenyl) tropane ([123I]IPT) were examined in brain SPECT studies (n
      = 20) of nonhuman primates. METHODS: Radiolabeling and purification of the
      iododestannylated trialkyltin percursor yielded the tracer at greater than 90%
      radiochemical purity and high (> 20,000 Ci/mmole) specific activity. Cynomologous
      monkeys were injected with 7.2 +/- 1.3 mCi (mean +/- s.d.) of the tracer, and
      serial 10-min images were acquired (total scan time = 177 +/- 22 min). Images
      were reconstructed as transaxial slices (2 mm) using restorative techniques
      (Wiener prefiltering). RESULTS: Radioactivity concentrated quickly in striatal
      regions (time of peak = 25 +/- 13 min) and cleared gradually thereafter (8.8 +/-
      4.6% hr). Striatal-to-cerebellar ratios of 2.6 +/- 1.5 (n = 19), 6.7 +/- 3.2 (n =
      20), 15.1 +/- 10.7 (n = 10) and 22.8 +/- 11.0 (n = 9) were observed at the time
      of peak and at 1, 2 and 3 hr p.i., respectively. In contrast, extrastriatal
      activity peaked earlier and at lower levels, cleared more rapidly and resembled
      cerebellar time-activity curves. Displacing doses of nonspecific antagonists of
      monoamine transporters (mazindol and beta-CIT) showed that 95% of specific
      [123I]IPT binding was reversible, while selective antagonists (e.g., paroxetine,
      nisoxetine and GBR 12909) demonstrated that striatal activity was specifically
      associated with dopamine transporters. CONCLUSION: These results indicate that
      [123I]IPT is a useful radioligand for in vivo SPECT imaging of striatal dopamine
      transporters.

PMID- 8523123
TI  - Carbon-11-d-threo-methylphenidate binding to dopamine transporter in baboon
      brain.
AB  - The more active d-enantiomer of methylphenidate (dl-threo-methyl-2-phenyl-2-(2
      piperidyl)acetate, Ritalin) was labeled with 11C(t1/2:20.4 min) to characterize
      its binding, examine its specificity for the dopamine transporter and evaluate it
      as a radio-tracer for the presynaptic dopaminergic neuron. METHODS: PET studies
      were carried out in the baboon. The pharmacokinetics of [11C]dl-threo
      methylphenidate, [11C]l-threo-MP and with its racemate ([11C]dl-threo
      methylphenidate, [11C]MP). Nonradioactive methylphenidate was used to assess the
      reversibility and saturability of the binding. GBR 12909, 3 beta-(4
      iodophenyl)tropane-2-carboxylic acid methyl ester (beta-CIT), tomoxetine and
      citalopram were used to assess the binding specificity. RESULTS: The ratio
      between radioactivity in the striatum and that in the cerebellum (ST/CB) after
      injection of [11C]d-threo-MP was higher than that for [11C]MP and [11C]l-threo-MP
      (3.3 for d-, 2.2 for racemic and 1.1 for l- in the same baboon). Most of the
      striatal binding of [11C]d-threo-MP was displaceable by injection of
      nonradioactive MP. Pretreatment with nonradioactive MP (0.5 mg/kg), GBR12909 (1.5
      mg/kg) and RTI-55 (0.3 mg/kg) markedly reduced striatal but not cerebellar uptake
      of [11C]d-threo-MP. In all cases, the ST/CB after pretreatment was reduced by
      about 60% compared to 43% for [11C]MP. The ratios of distribution volumes at
      steady-state for the ST/CB for the three separate studies in the same baboon were
      reduced by about 50%, as compared with 37% for [11C]MP. In contrast, pretreatment
      with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg) did not change [11C]d-threo
      MP kinetics; the ST/CB after pretreatment was similar to that for the control.
      CONCLUSION: These results demonstrate the saturable, reversible and specific
      binding of [11C]d-threo-MP to the dopamine transporter on the baboon brain,
      suggesting that [11C]d-threo-MP will be a useful PET tracer for the presynaptic
      dopaminergic neuron in living human brain.

PMID- 8523124
TI  - Technetium-99m labeling of DNA oligonucleotides.
AB  - Single-stranded RNA and DNA oligonucleotides may be useful as
      radiopharmaceuticals for antisense and other in vivo applications if convenient
      methods for stably attaching radionuclides such as 99mTc can be developed.
      METHODS: To radiolabel DNA with 99mTc, we have used the hydrazino nicotinamide
      (SHNH) moiety developed elsewhere. The diethylenetriaminepentacetic acid (DTPA)
      chelate was used to label DNA with 111In for comparison. Complementary 22-base,
      single-stranded oligonucleotides were obtained, each with a primary amine
      attached to either 3' or 5' end with a biotin moiety on the opposite end. The DNA
      was conjugated with SHNH by a N-hydroxysuccinimide derivative with DTPA by the
      cyclic anhydride. RESULTS: Reversed-phase HPLC analysis showed that essentially
      complete conjugation was achieved in both cases. The purified SHNH-DNA was
      radiolabeled with 99mTc by transchelation from glucoheptonate at labeling
      efficiencies of up to 60% and DTPA-DNA with 111In acetate at up to 100%
      efficiency. After labeling, the ability of the DNAs to bind to streptavidin
      through the biotin moieties and to hybridize with their complementary DNA in
      saline was retained for both radiolabels as determined by size-exclusion HPLC
      analysis. HPLC radiochromatograms of serum incubates showed a shift to 99mTc, but
      not 111In, to a high molecular weight, strongly suggesting serum protein binding
      in the former case only. Low-molecular weight degradation products were seen with
      111In, but not with 99mTc and may be related to the use of phosphodiester-linked
      oligonucleotides. As a further measure of label stability, the DNAS were bound to
      streptavidin-conjugated magnetic beads and incubated in fresh 37 degrees C human
      serum. Less than 4% of 99mTc and 14% of 111In was lost in 24 hr. CONCLUSION:
      Amino-modified, single-stranded DNA can be stably radiolabeled with 99mTc by the
      SHNH moiety without loss of function.

PMID- 8523125
TI  - In vitro and in vivo evaluation of copper-64-octreotide conjugates.
AB  - Copper-64 (T1/2 = 12.8 hr) is a reactor-produced radionuclide that has
      applications in both nuclear medicine imaging by PET and radiotherapy.
      Octreotide, a somatostatin receptor ligand, has been conjugated with TETA and
      CPTA, labeled with 64Cu, evaluated both in vitro and in vivo and compared to
      111In-DTPA-D-Phe1-octreotide. METHODS: The carboxylic acid moieties on the T
      bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the
      linking agents hydroxybenzotriazol (HOBT) and diisopropylcarbodiimide (DIC).
      Receptor binding assays on all three radiolabeled octreotide conjugates were
      accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo
      biodistribution was performed using normal Sprague-Dawley rats and Lewis rats
      carrying a somatostatin receptor-positive rat pancreatic tumor. RESULTS: The
      binding affinities of 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide
      in AtT20 cell membranes were both greater than 111In-DTPA-D-Phe1-octreotide (Kd,
      78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1
      octreotide was localized primarily in the liver. Copper-64-TETA-D-Phe1
      octreotide, similar to 111In-DTPA-D-Phe1-octreotide, had moderate uptake in the
      kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948
      pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1
      octreotide had uptake in tumors comparable to better than 111In-DTPA-D-Phe1
      octreotide. CONCLUSION: Of the two 64Cu-labeled octreotide conjugates evaluated,
      64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin
      receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64
      TETA-D-Phe1-octreotide binds to the somatostatin receptor with five times the
      affinity of 111In-octreotide, has desirable clearance properties (renal clearance
      with rapid excretion) and is a potential agent for PET imaging of somatostatin
      receptors.

PMID- 8523126
TI  - Difference analysis of antifibrin images in the detection of deep venous
      thrombosis.
AB  - This study was designed to test the hypothesis that the detection of non-blood
      pool localization due to deep venous thrombosis uptake can be enhanced by
      computer processing. METHODS: Immediate blood-pool and 90-min delay images from
      25 patient studies obtained with 99mTc T2G1s antifibrin were paired into 125
      image sets (5/pt, including A, P knees, A, P calves and A thighs). After
      spatially aligning the image pairs, the blood-pool activity obtained from the
      immediate image was removed from the delayed image to produce a "clot only"
      image. Unprocessed data (UnP) and computer processed images (CmP) were presented
      to novice readers as part of a receiver operator characteristic (ROC) comparison
      study. The image interpreters were asked to provide independent diagnostic
      assessment at 250 limb sites using both datasets. Image intensity and color scale
      mappings were freely adjustable. Three readers were presented with images
      adjusted with optimal image contrast as judged by an observer with knowledge of
      the correct response. RESULTS: The area under the ROC curve (Az), a measure of
      the method's accuracy, for these readers was 88.5% (UnP) and 88.8% (CmP) (p =
      ns). Four readers whose images were not optimized showed Az of 79.1% (UnP) and
      90.7% (CmP) (p < 0.05). Average diagnostic decision time for all readers, per
      limb site, was 18.2 +/- 7.8 sec, m +/- s.e.m., (UnP) and 7.6 +/- 4.6 sec (CmP).
      CONCLUSION: Novice reader accuracy is improved with computer processed images
      when image intensity and contrast factors are important. Computer processing can
      provide "clot" images that minimize nonspecific blood background activity and
      allow greater interpreter decision speed/confidence.

PMID- 8523127
TI  - Intermodality, retrospective image registration in the thorax.
AB  - The purpose of this study was to develop an accurate, retrospectively applicable
      procedure for registering thoracic studies from different modalities in a short
      amount of time and with minimal operator intervention. METHODS: CT and PET
      studies were acquired from six patients. The pleural surfaces in both image sets
      were determined by segmenting based on 50% of the maximum soft-tissue value in
      the study. These surfaces were converted into three-dimensional volumes and used
      to register the CT and PET studies in three dimensions using a sum of least
      squares fitting approach. The registered PET study was then displayed in a hot
      metal scale overlayed on top of the gray scale CT study. The accuracy of the fit
      was evaluated through a phantom study and preliminary clinical evaluation.
      RESULTS: A phantom study was performed to determine the limits of this technique.
      The accuracy was determined to be less than 2.3 mm in the x and y direction and 3
      mm in the z direction. Preliminary clinical evaluation was also performed with
      encouraging results. CONCLUSION: This technique accurately registers PET and CT
      images of the thorax, retrospectively, without the need for external fiducial
      markers or other a priori action.

PMID- 8523128
TI  - Cerebral blood flow measurement with iodine-123-IMP SPECT, calibrated standard
      input function and venous blood sampling.
AB  - We previously reported simple methods for measuring cerebral blood flow (CBF)
      with 123l-labeled N-isopropyl-p-iodoamphetamine (IMP) and SPECT: table look-up
      method and autoradiography. With these methods, the arterial input function is
      obtained by calibrating the standard input function using one-point arterial
      blood sampling 10 min after IMP infusion. In this study, we sought to determine
      if these approaches can be as successful when used with venous blood sampling.
      METHODS: After IMP infusion, simultaneous arterial and venous blood samples were
      drawn from 30 subjects without heart or lung disease. RESULTS: The activity
      ratios of venous whole blood from the cubital vein to arterial blood were 0.75 +/
      0.09, 0.77 +/- 0.10, 0.78 +/- 0.03 and 0.83 +/- 0.11, respectively, at 10, 20,
      30 and 50 min after IMP infusion. Venous blood activities were always 20% lower
      than the artery values over 50 min. When blood was sampled from the dorsal hand
      vein, however, the respective ratios were 0.92 +/- 0.03, 0.93 +/- 0.05, 0.97 +/-
      0.04 and 0.98 +/- 0.08 after 10, 20, 30 and 50 min. Furthermore, when the palm
      was exposed to heat during the sampling period, blood activity levels increased
      to 0.92 +/- 0.04, 0.96 +/- 0.04, 0.99 +/- 0.05 and 0.98 +/- 0.03. Thus, venous
      blood activities were consistent with arterial activity, presumably because of
      the numerous arteriovenous anastomoses in the palm. Optimal times for venous
      blood sampling, with and without palm heating, were determined by error analysis
      to be 15 and 20 min, respectively, after IMP infusion. CONCLUSION: Venous blood
      sampling from the dorsal hand can be substituted for arterial blood sampling in
      IMP-CBF studies.

PMID- 8523129
TI  - Cerebral blood flow quantitation in clinical routine studies: how far have we now
      come?

PMID- 8523130
TI  - A nonimaging scintillation probe to measure penile hemodynamics.
AB  - We have developed a penile nonimaging scintillation (PNIS) probe consisting of a
      plastic well-type scintillation crystal interfaced to a portable computer and
      acquisition board. This report describes the design of the PNIS probe,
      performance characteristics, mode of usage and illustrative results which
      demonstrate its capabilities. METHODS: With the PNIS probe, penile blood-pool
      studies were performed in nine patients utilizing 3.7 MBq (100 microCi)
      autologous 99mTc-labeled red blood cells (RBCs). Venous blood standards were
      assayed to enable conversion of the count rate to volummetric measurements.
      Washin of peripherally administered 99mTc-RBCs was mathematically analyzed to
      estimate penile blood volume and cavernosal flow rate in the flaccid state. The
      rate of change of penile blood volume after intracavernosal vasodilators was used
      to generate measures of stimulated flow. RESULTS: A major advantage of this
      device over the gamma-camera is a 3300-fold increase in count rate sensitivity,
      which allows for markedly improved temporal resolution while significantly
      reducing the radiopharmaceutical dosage. Additionally, the PNIS probe is
      portable, economical and is not dependent on operator-defined regions of
      interest. Count rate sensitivity is relatively constant within the bore, with the
      exception of the proximal region adjacent to the opening, where geometric
      efficiency is reduced. CONCLUSION: The PNIS probe is an effective device for
      measuring penile activity in radionuclide studies, allowing for acquisition of
      time-activity curves of the penis during flaccid washin of peripherally labeled
      red blood cells and after pharmacologic stimulation to induce erection.

PMID- 8523131
TI  - Assessment of energy-weighted acquisition in SPECT using ROC analysis.
AB  - Energy-weighted acquisition is a technique for reducing Compton scatter effects
      in nuclear medicine images. The effect of energy-weighted acquisition on
      SPECT99mTc images was evaluated by comparing the energy-weighted acquisition
      images with those obtained using a 20% photopeak energy window. METHODS: SPECT
      images were compared using receiver operator characteristic (ROC) experiments
      testing the observer's ability to perform a pseudoclinical task. The tasks were
      detecting cold lesions within a uniform background and cold lesions within images
      created with a tomographic brain phantom. RESULTS: ROC analysis for each phantom
      produced different results. No significant difference was found between the two
      acquisition techniques in detecting cold lesions on uniform backgrounds. Energy
      weighted acquisition improved cold lesion detection significantly within the
      brain phantom in comparison with 20% photopeak acquisition. CONCLUSION: Lesion
      detection in 99mTcSPECT images can be improved using energy-weighted acquisition.
      This improvement, however, is dependent on the nature of the object being imaged.
      Images with structure show improved detection, whereas uniform images do not.

PMID- 8523132
TI  - Pharmacokinetics and scintigraphy of indium-111-DTPA-MOC-31 in small-cell lung
      carcinoma.
AB  - Radiolabeled MOC-31 retains its immunoreactivity and shows good in vivo
      immunolocalization to human SCLC xenografted in nude rats. METHODS: We evaluated
      the immunotargeting properties and safety of 111In-labeled monoclonal antibody
      (MAb) MOC-31 (125 MBq, 5 mg) in six patients with histologically proven small
      cell lung cancer (SCLC). Scintigraphy and pharmacokinetics were performed up to 3
      days after injection. RESULTS: No adverse reactions were found after injection of
      MAb MOC-31. Pharmacokinetics obtained from plasma radioactivity showed plasma
      disappearance described most properly by a monoexponential model with a mean half
      life value of 17.0 +/- 1.4 hr. HPLC analysis documented the monomeric MOC-31
      without evidence of immune complexes or radioactive lower molecular weight
      fractions. Mean 24-hr urinary excretion of radioactivity was 4.3% of the injected
      dose. Scintigraphy detected primary tumor or metastases in five of six patients.
      Localization of radioactivity in normal tissue was restricted, but additional
      experiments need to be performed to elucidate possible cross-reactivity of MOC-31
      with normal tissue in vivo. CONCLUSION: Preliminary results justify further
      studies to reveal the possible usefullness of radiolabeled MOC-31 in the
      therapeutic and diagnostic management of SCLC.

PMID- 8523133
TI  - Dosimetry of copper-64-labeled monoclonal antibody 1A3 as determined by PET
      imaging of the torso.
AB  - We present biodistribution and dosimetry results for 64Cu-benzyl-TETA-MAb 1A3
      from 15 human subjects injected with this tracer as determined by serial PET
      imaging of the torso. METHODS: PET imaging was used to quantify in vivo tracer
      biodistribution at two time points after injection. Absorbed dosimetry calculated
      using MIRD-11 and the updated MIRDOSE3 was compared with estimates obtained using
      rat biodistribution data. RESULTS: By measuring activity concentrations in the
      torso, and extrapolating for the whole body using standard organ and tissue
      volumes, we were able to account for 93% of the injected radiopharmaceutical over
      a range of imaging times from 0 to 36 hr postinjection. Based on PET imaging and
      the MIRD-11 schema, the liver and spleen are the critical organs with average
      absorbed doses of 0.12 and 0.10 mGy/MBq (0.44 and 0.39 rad/mCi). The revised
      MIRDOSE3 scheme yields similar values for these and other organs but also results
      in a dose of 0.14 mGy/MBq (0.53 rad/mCi) to the heart wall. In the rat, the large
      intestine is the critical organ at 0.14 mGy/MBq (0.52 rad/mCi), while liver and
      kidneys each receive 0.11 mGy/MBq (0.41 rad/mCi). Some disparities in absorbed
      doses determined by these methods are evident but are a result of dissimilar
      biodistributions in rats and humans. For most organs, rat extrapolated values are
      higher than the human measurements with PET. CONCLUSION: This study shows that
      torso PET imaging can quantitatively measure the whole-body biodistribution of a
      radiopharmaceutical as long as it has relatively slow pharmacokinetics.

PMID- 8523134
TI  - Biodistribution and dosimetry of indium-111-polyclonal IgG in normal subjects.
AB  - Indium-111-polyclonal IgG is a new imaging agent of infection and inflammation
      that has been developed as a possible replacement for radiolabeled leukocytes. We
      undertook a study to determine the safety, biodistribution and dosimetry of the
      agent in normal subjects. METHODS: Twelve normal male volunteers with an average
      age of 34 yr (range 21-55 yr) were studied. Each was injected with 1.22-1.47 mCi
      111In-labeled polyclonal IgG; digital whole-body images, in addition to blood,
      urine and fecal samples, were obtained immediately after injection and at 6, 24,
      48, 72, 96 and 120 hr. Whole-body counts, as well as individual organ data
      obtained by outlining regions of interest, were measured. Blood, urine and fecal
      counting were done in a well counter and compared to known standards; dosimetry
      calculations were performed with the MIRD technique. RESULTS: The mean whole
      blood activity had a two-phase disappearance curve: the T1/2I was 11.4 hr (61.1%)
      and the T1/2II was 112.5 hr (38%). Twelve percent of the dose was excreted in the
      urine and 1.14% in the feces. Skeletal muscle had the highest percentage of
      uptake, followed by the bone marrow, liver and lungs; the spleen showed less than
      1% uptake. Activity in the lungs varied with time, falling by 37% after 18 hr and
      by 68% after 72 hr. Dosimetry calculations indicated that the highest absorbed
      dose was to the liver (1.42 rad/mCi) followed by the testes (1.23 rad/mCi) and
      red marrow (0.976 rad/mCi). The total-body dose was 0.467 rad/mCi, with an
      effective dose equivalent of 790.84 mrem. CONCLUSION: The biodistribution of
      111In IgG is similar to that of 99mTc-HMPAO-labeled leukocytes. Activity in the
      liver, kidneys and GI tract may make evaluation of infection in these regions
      difficult. The dosimetry data indicate that adequate doses can be administered
      for clinical imaging without exposing the patient to excessive radiation.

PMID- 8523135
TI  - Comprehensive analysis of the results of the PIOPED Study. Prospective
      Investigation of Pulmonary Embolism Diagnosis Study.
AB  - The goals of this review were to summarize the published data from the National
      Heart, Lung and Blood Institute sponsored Prospective Investigation of Pulmonary
      Embolism Diagnosis (PIOPED) study, present new data from the entire population
      and provide a comprehensive criteria for ventilation-perfusion (V/Q) lung scan
      interpretation. METHODS: Data from the PIOPED frequent user tape and journal
      articles published between 1990 and 1994 and indexed on Medline that presented
      data from the PIOPED study were reviewed. RESULTS: A normal V/Q lung scan
      excludes the diagnosis of clinically significant PE. The usefulness of the V/Q
      lung scan was optimized when interpreted as representing a very low, low or high
      probability of PE with a concordant clinical likelihood of PE. Patients with a
      V/Q lung scan interpreted as representing an intermediate probability of PE or
      patients with discordant clinical likelihood of PE and lung scan interpretation
      will often require further investigations to diagnose or exclude acute venous
      thromboembolism. CONCLUSION: The results of the PIOPED study support the use of
      V/Q lung scanning in the diagnostic evaluation of patients with suspected PE.
      Amendments to the original PIOPED interpretation criteria should reinforce the
      role of V/Q lung scanning in patients with suspected PE.

PMID- 8523136
TI  - PET scanners for small animals.

PMID- 8523137
TI  - What is the predictive value of increased technetium-99m-HMPAO uptake for brain
      survival/necrosis in the acute stage of ischemic stroke?

PMID- 8523138
TI  - Radiation risk and nuclear medicine: An interview with a Nobel Prize winner.

PMID- 8523139
TI  - A model for collegiality among staff nurses in acute care.
AB  - For decades, collegiality has persisted as an important issue for nurses,
      especially for nurse leaders. In an increasingly interdependent healthcare
      environment, collegial relationships among nurses and other health professionals
      are vital to achieving the goal of clinically integrated care. Nurse
      administrators greatly influence decision making among health professionals by
      monitoring and facilitating their interactions. The model used in this study
      contributes to an understanding of the factors that affect collegiality among
      nurses and potentially among other members of the healthcare team.

PMID- 8523140
TI  - Coordination as a critical element of managed care.
AB  - Although the concept of coordination is not new to nursing, little is known about
      how it contributes to cost-effective patient care outcomes. The authors examined
      the mechanisms used by staff nurses to coordinate patient care services in
      practice environments characterized by low, moderate, and high levels of
      uncertainty. Regardless of practice environment conditions, nurses used the same
      mechanisms to coordinate patient care. These findings suggest a potential for
      inadequate communication among providers, poor coordination of services, and lost
      efficiency. Strategies to improve coordination of patient care services are
      discussed.

PMID- 8523141
TI  - Reducing intensive care unit length of stay. A stepdown unit for first-day heart
      surgery patients.
AB  - The restructuring of healthcare delivery systems has increased the demand for
      successful, low-cost, alternative approaches to providing care. The authors
      detail the design, implementation, and evaluation of one alternative approach for
      delivery of care to thoracic surgery patients. The authors describe the use of a
      stepdown unit for the care of patients 24 to 36 hours after cardiothoracic
      surgery.

PMID- 8523142
TI  - Utilization of advanced practice nurses in healthcare systems and multispecialty
      group practice.
AB  - Cost-effective strategies for delivering primary care require the appropriate mix
      of healthcare providers. The authors define the scope of practice for the
      advanced practice nurse. Results of a nationwide survey of 26 large healthcare
      systems and multispecialty group practices are presented. Findings from these
      practice settings are contrasted with those previously reported in the
      literature. Implications for the future are discussed.

PMID- 8523143
TI  - Shared governance. From vision to reality.
AB  - Quality patient care is best provided by competent clinical staff members who are
      committed to their work, organizational values, and goals, and who maintain
      employment over time. Shared governance has provided the framework for clinical
      nurses to become more committed to their practice through decision making and to
      assume accountability for the outcomes of their decisions. At a tertiary teaching
      facility, shared governance resulted in increased job satisfaction, commitment,
      and retention among staff nurses. The authors describe the journey from creation
      of the shared governance vision to reality, and the impact of the changes.

PMID- 8523144
TI  - Guiding principles for nurse executives.

PMID- 8523145
TI  - Breaking the cycle of aggression.
AB  - The continuous quality improvement literature has taught us that it is important
      to test out theories about the cause of a problem before generating solutions to
      the problem. The project described in this article illustrates the value of this
      systematic analysis as it applies to decreasing injuries related to aggressive
      actions of patients.

PMID- 8523146
TI  - Preparing for redesign education.

PMID- 8523147
TI  - A Christmas Carol. A case study for McGregor's motivation theories X and Y.

PMID- 8523148
TI  - Initiation, integration, and innovation.

PMID- 8523149
TI  - Alcohol withdrawal: a nationwide survey of inpatient treatment practices.
AB  - OBJECTIVE: To describe current practices employed in the inpatient treatment for
      alcohol withdrawal. DESIGN: Survey. SETTING: Inpatient alcoholism treatment
      programs in the United States. PARTICIPANTS: Medical directors of 176 (69%) of
      257 eligible programs randomly selected from a national listing. RESULTS: The
      medical directors estimated that of all inpatients treated for alcohol withdrawal
      at the programs, 68% received one of the following medications. Benzodiazepines,
      including the long-acting chlordiazepoxide (33%) and diazepam (16%), and less
      frequently the short-acting oxazepam (7%) and lorazepam (4%), were the most
      commonly used agents. Barbiturates (11%), phenytoin (10%), clonidine (7%), beta
      blockers (3%), carbamazepine (1%), and antipsychotics (1%) were less frequently
      given. Drug was most often given on a fixed dosing schedule with additional
      medication "as needed" (52% of the programs). Only 31% of the programs routinely
      used a standardized withdrawal severity scale to monitor patients. Mean duration
      of sedative treatment was three days; inpatient treatment, four days. Use of
      fixed-schedule regimens was associated with longer sedative treatment (mean four
      vs three days, p < 0.01). Northeast census region location and psychiatrist
      program director were significantly associated with longer sedative and inpatient
      treatment duration. CONCLUSIONS: The most commonly reported regimen for alcohol
      withdrawal included three days of long-acting benzodiazepines on a fixed schedule
      with additional medication "as needed." Standardized monitoring of the severity
      of withdrawal was not common practice. The directors reported using a variety of
      other regimens, some not known to prevent the major complications of withdrawal.
      Although geographic location and director specialty were significantly associated
      with treatment duration, much of the variation in treatment for alcohol
      withdrawal remains unexplained.

PMID- 8523150
TI  - Health-related messages in consumer magazine advertising.
AB  - OBJECTIVE: To characterize the patterns of health-related messages in consumer
      advertising from U.S. magazines. DESIGN: Observational survey of advertisements
      occupying a third of a page or more from the January 1994 issues of the 11 most
      popular consumer magazines. MEASUREMENTS AND MAIN RESULTS: Health messages were
      present in 22.8% (85/372) of all the advertisements reviewed. Of the
      advertisement categories (prescription medication, over-the-counter medication,
      exercise-related product, health service, health device, diet/health-related
      food, and other), over-the-counter medications were the most common among the
      advertisements that had health messages (32.9%, 28/85) (7.5% of the total
      advertisements, 28/372). The five advertisements for prescription medications
      were duplications of two different advertisements, one for a hair promotion
      product and one for hormone replacement therapy. Products related to diet and
      exercise together represented 29.4% (25/85) of all advertisements with health
      messages. Three advertisements (3.5%) were for health devices, and five (5.9%)
      were for health services. CONCLUSIONS: Health-related messages are frequent in
      consumer advertising. The effects of health marketing on consumer protection,
      health care costs, and the physician-patient relationship are discussed.

PMID- 8523151
TI  - Medical specialists prefer to withdraw familiar technologies when discontinuing
      life support.
AB  - OBJECTIVE: To assess how members of different specialties vary in their decisions
      about which form of life support to withdraw. The hypothesis was that each
      specialty would be more comfortable withdrawing its "own" form of life support
      relative to other forms and other specialties. DESIGN: Mail survey. SETTING: 24
      medical centers. PARTICIPANTS: 225 specialists in six specialties and 225
      comparison physicians randomly matched according to percentage of time devoted to
      clinical practice. MEASUREMENTS: The six specialties were linked with six life
      sustaining technologies related to their special expertise: 1) pulmonologists
      with mechanical ventilation, 2) nephrologists with hemodialysis, 3)
      gastroenterologists with tube feedings, 4) hematologists with blood products, 5)
      cardiologists with intravenous vasopressors, and 6) infectious disease
      specialists with antibiotics. The subjects ranked different forms of life support
      in the order in which they would prefer to withdraw them. They also expressed
      their preferences in response to hypothetical clinical vignettes. RESULTS: In
      five of the six specialties, the specialists had a relative preference for
      withdrawing their "own" form of life support, compared with the preferences of
      the comparison physicians. Overall, the physicians tended to prefer withdrawing a
      form of life support closely linked with their own specialty. CONCLUSIONS: Just
      as some specialist physicians tend to reach for different technologies first in
      treating patients, they also tend to reach for different technologies first when
      ceasing treatment. Specialists' preferences for different ways to withdraw life
      support not only may reflect a special understanding of the limits of certain
      technologies, but also may reveal how ingrained are physicians' patterns of
      practice.

PMID- 8523152
TI  - Primary care physician productivity: the physician factor.
AB  - OBJECTIVES: To model physician productivity as a function of clinic (support
      system) characteristics and physician characteristics and to model the time a
      physician spends with the patient as a function of patient characteristics.
      DESIGN: Observational study. SETTING: A general medicine clinic of a university
      affiliated Veterans Affairs medical center. PATIENTS: A cohort of 2,520 patients
      having 2,721 consecutive outpatient visits to 56 physicians. MAIN OUTCOME
      MEASURES: Physician productivity defined as patients seen/physician/hour and time
      (minutes) spent with the patient. RESULTS: Physicians saw a mean (+/- SD) of 1.62
      +/- 0.68 patients/hour. Clinic characteristics explained 8.2% of the variability
      of session-specific physician productivity. Controlling for clinic
      characteristics, a factor representing the physician explained an additional
      55.4%. A model for overall physician productivity, using physician
      characteristics, explained 84.9% of the variance, and time spent with the patient
      was an important predictor. Modeling physician time with patients, patient
      characteristics accounted for only 7% of the variability. Controlling for patient
      characteristics, the individual physician again provided the greatest explanatory
      power, an additional 22.8% of the variability. CONCLUSIONS: Physicians' practice
      patterns, rather than clinic or patient characteristics, may account for most of
      the variation in physician productivity. Given the magnitude of the influence of
      individual practice patterns, interventions to increase productivity need to
      consider methods to affect physician behavior.

PMID- 8523153
TI  - Measuring attending physician performance in a general medicine outpatient
      clinic.
AB  - OBJECTIVE: To determine which aspects of outpatient attending physician
      performance (e.g., clinical ability, teaching ability, interpersonal conduct)
      were measurable and separable by resident report. DESIGN: Self-administered
      evaluation form. SETTING: University internal medicine resident continuity
      clinic. PARTICIPANTS: All residents with their continuity clinic at the
      university hospital evaluated the two attendings who staffed their clinic for the
      academic years of 1990-1991, 1991-1992, and 1992-1993 (average of 85 total
      residents per year). The overall response rate was 74%. ANALYSIS: Exploratory
      analyses were conducted on a preliminary evaluation form in the first two years
      of the study (236 evaluations of 20 different clinic attendings) and confirmatory
      analyses using factor analysis and generalizability analysis were performed on
      the third year's data (142 evaluations of 15 different clinic attendings).
      Analysis of variance was used to evaluate factors associated with evaluation
      scores. RESULTS: Analyses demonstrated that the residents did not distinguish
      between the attendings' clinical and teaching abilities, resulting in a single
      four-item scale that was named the Clinical/Teaching Excellence Scale, measured
      on a five-point scale from poor to outstanding (Cronbach's alpha = 0.92). A large
      amount of the variance for this scale score was associated with attending
      identity (adjusted R2 = 46%). However, two alternative approaches to evaluating
      the performance of the attending (preference for him or her to the "average"
      attending and perceived impact of the attending on residents' clinical skills)
      did not provide useful information independent of the Clinical/Teaching
      Excellence Scale. The ratings of three separate conduct scales [availability in
      clinic (Availability Scale), treating residents and patients with respect
      (Respect Scale), and time efficiency in staffing cases (Slow Staffing Scale)]
      were separable from each other and from the rating of clinical/teaching
      excellence. For the Clinical/Teaching Excellent Scale, as few as four evaluations
      produced good interrater reliability and eight evaluations produced excellent
      reliability (reliability coefficients were 0.70 and 0.84, respectively).
      CONCLUSIONS: Although this evaluation instrument for measuring clinic attending
      performance must be considered preliminary, this study suggests that relatively
      few attending evaluations are required to reliably profile an individual
      attending's performance, that attending identity is associated with a large
      amount of the scale score variation, and that special issues of attending
      performance more relevant to the outpatient setting than the inpatient setting
      (availability in clinic and sensitivity to time efficiency) should be considered
      when evaluating clinic attending performance.

PMID- 8523154
TI  - Safety of pneumococcal revaccination.
AB  - Indications for pneumococcal polysaccharide revaccination include highest-risk
      patients vaccinated more than six years previously, but there is controversy
      regarding revaccination of patients with chronic medical conditions and
      revaccination of the elderly. The object of the study was to investigate whether
      revaccination with the pneumococcal polysaccharide vaccine would cause
      significant adverse reactions. 151 patients were revaccinated and completed a
      questionnaire concerning the 72 hours after the injection. Valid data were
      obtained from 127 patients. Mild systemic reactions varied from 4% to 8% and
      local reactions varied from 40% to 60%, which is not different from the reported
      reaction with the initial vaccination. This profile of adverse reactions after
      revaccination should minimize concerns about revaccination.

PMID- 8523155
TI  - Omeprazole use at an urban county teaching hospital.
AB  - To determine the appropriateness of use of omeprazole, all outpatient
      prescriptions over one year from a single county hospital pharmacy were analyzed.
      Appropriateness of omeprazole use was assessed by literature review and expert
      opinion. Two hundred twenty-one prescriptions were evaluated; 112 (56%) were
      inappropriate. Women received more inappropriate prescriptions (61% vs 44%, p =
      0.01) and received endoscopy less frequently (52% vs 71%, p < 0.02) than did men.
      When age, gender, and prescribing clinic were examined as predictors of
      inappropriate use, only gender was significant (OR = 2.01, 95% CI = 1.52-2.66).
      This study, from a single institution, showed a high rate of inappropriate
      omeprazole use.

PMID- 8523156
TI  - Skin cancer control practices among physicians in a university general medicine
      practice.
AB  - Physician counseling about sun protection and routine screening for skin cancer
      in high-risk individuals have been widely recommended. The purpose of this study
      was to assess the skin cancer control practices and knowledge among physicians in
      a university-based general medicine practice. Fifty-two physicians completed a
      survey on attitudes toward, behaviors in, and knowledge of skin cancer control.
      In addition, the ability of general medicine residents and attending physicians
      to correctly identify and make biopsy recommendations for ten photographed skin
      lesions was compared with that of third-year medical students and dermatology
      residents and attendings. The results of the survey illustrate a need for
      improving primary care physicians' knowledge and identification of skin cancer
      risk factors, and increasing the frequency and consistency with which they
      perform skin cancer prevention counseling and complete skin examination in high
      risk patient groups.

PMID- 8523157
TI  - Who gets repeat screening mammography: the role of the physician.
AB  - To determine rates of, and explore physician factors associated with, repeat
      mammography, administrative data for 791 women aged 50 years and older were
      examined. Three-fourths of the women (73%) received repeat mammography (i.e., a
      second mammogram was obtained within six to 18 months of the first). Provider
      factors associated with higher repeat mammography rates were: being a woman,
      practicing in the women's health group rather than the general internal medicine
      service, and being a fellow or an attending physician (p-values < 0.01). Patients
      of women attendings/fellows had higher repeat mammography rates than did those of
      men attendings/fellows, men residents, and women residents. Characteristics
      (gender, level of training) of providers strongly influence their patients'
      screening behavior.

PMID- 8523158
TI  - Current treatment for alcohol withdrawal.

PMID- 8523159
TI  - When you've seen how one doctor works, you've not seen how all doctors work.

PMID- 8523160
TI  - Assessing clinician-teachers in the outpatient clinic.

PMID- 8523161
TI  - Drug utilization evaluation: is big brother watching?

PMID- 8523162
TI  - "Reverse" cross-cultural medicine.

PMID- 8523163
TI  - Physician visit frequency in Alzheimer's disease.

PMID- 8523164
TI  - [Eighteen cases of tortuosity of the internal carotid--usefulness of MR
      angiography in diagnosis].
AB  - There have been few reports on tortuosity of the internal carotid exhibiting
      pulsation or swelling in the pharyngeal wall. Because this disease carries the
      risk of causing massive hemorrhage at the time of incision of a peritonsillar
      abscess, surgical treatment of the adenoids, or tonsillectomy, otolaryngologists
      should be aware of the existence of this disorder as a risk factor. We
      encountered tortuosity of the internal carotid in the pharynx in 18 cases over an
      approximately two year period. Females (15 cases) outnumbered males (3 cases),
      and the mean age was 68 years at the time of diagnosis. There was no right-to
      left difference in terms of the incidence of the disease. The complication of
      hypertension was noted in 10 cases. MR-Angiography (MRA) was performed in 13
      cases, and very clear images were obtained; this technique was useful for
      diagnosing this disorder. For the most part, contrast angiography has been
      employed for the diagnosis of this disorder, but various complications, including
      deaths, have been reported. As the incidence of tortuosity of the internal
      carotid is high in the elderly, it is thought that any complication which may
      occur has the potential to become serious. Non-invasive diagnostic techniques are
      thus recommended. MRA is absolutely non-invasive, and we therefore believe that
      this technique should be the modality of first choice for diagnosing tortuosity
      of the internal carotid.

PMID- 8523165
TI  - [A study on the reliability of evoked response audiometry in infants below one
      year of age; a long-term follow-up].
AB  - The reliability of brainstem evoked response audiometry (ERA) as an objective
      audiometric study was evaluated in long term follow-up infants with moderate to
      severe sensorineural hearing loss. None of the infants had either brain damage
      (cerebral palsy, mental retardation) or other severe complications (genetic
      diseases). The thresholds of ERA at 1 kHz and 4 kHz were measured in 234 infants
      below one year of age, from 1983 to 1990, in our hospital. These infants were
      followed-up to the age when conditioned oriented response audiometry (COR) and
      play audiometry could be conducted. Pure tone thresholds obtained by COR and play
      audiometry were compared with those of ERA. In addition, speech problems in these
      patients were evaluated. In all of those infants, hearing aids were fitted before
      one year of age to achieve early habilitation. As a results, ERA was found to be
      a reliable and efficacious test for determining auditory thresholds, and
      providing hearing aids for early habilitation in one-year old infants with
      moderate to severe sensorineural hearing loss.

PMID- 8523166
TI  - [Evaluation of blood-group-related carbohydrate antigens in thyroid neoplasms].
AB  - An immunohistochemical study using a panel of monoclonal antibodies (mAbs)
      against blood group A, B, H and Lewis antigens Le(a), Le(b), Le(x) and Le(y) and
      lectins, such as PNA, VVA-B4 and UEA -1, was carried out to investigate the
      aberrant expression of carbohydrate antigens in formalin-fixed, paraffin-embedded
      tissue sections of thyroid neoplasms. The tissues examined consisted of 26
      papillary carcinomas, seven follicular adenomas, seven follicular carcinomas, one
      anaplastic carcinoma and one medullary carcinoma. MAbs against A, B and H
      antigens reacted strongly with papillary carcinomas from most of the individuals
      studied (22 of 26 individuals) and their reactivity corresponded well to the
      blood groups of individuals. In follicular adenomas and carcinomas, these mAbs
      reacted weakly with a small number of neoplastic cells from two of seven, and
      four of seven individuals, respectively. Positive staining with mAbs against
      Le(a) and Le(b) antigens was found in almost all papillary carcinomas. On the
      contrary, these mAbs rarely reacted with cells from follicular adenomas and
      carcinomas. T and Tn antigens which were recognized by PNA and VVA-B4,
      respectively, were only weakly expressed in a limited number of cells from the
      thyroid neoplasms. Normal cells adjacent to malignant cells were not stained by
      any of the stains used in this study. These results are discussed in light of our
      recent findings that polylactosamine structures produced in papillary carcinomas
      are quite different from those expressed in other types of neoplasms.

PMID- 8523167
TI  - [Effect of alpha and beta-adrenergic agonists on methacholine-induced nasal
      secretion in man].
AB  - To examine the roles of alpha-adrenergic, beta-adrenergic and cholinergic
      agonists on the nasal secretion mechanism, the author repeated nasal methacholine
      (Mch, 1 time 20 mg) challenges ten times at 10-min intervals in 13 healthy male
      subjects. As it was difficult to obtain a sufficient amount of nasal secretion
      for analysis using simple nasal provocation tests with alpha-and beta-adrenergic
      agonists before repeated Mch challenges, alpha-adrenergic (phenylephrine, Phe, 2
      mg) and beta-adrenergic (isoproterenol, Iso, 0.2 mg) agonists were administered
      into both nostrils. The effects of these agents on the volume of nasal secretions
      (Vol), the fucose volume (Fu, an index of glandular secretion) and the albumin
      volume (Alb, an index of vascular permeability) in the Mch induced nasal
      secretions were analyzed each time. Repeated Mch challenges revealed that the
      initial challenge produced the largest response as reflected by the Vol, Fu and
      Alb of the secretions, and by Vol and Fu production being almost constant during
      the 10 repetitions of Mch challenge at 10-min intervals. However, Alb
      demonstrated the greatest decrements. Phe administration before Mch challenges
      gave rise to Fu increasing more markedly while Alb was unchanged. On the other
      hand, that of Iso before, produced greater decreases in Vol, Fu and Alb levels.
      Therefore, it is suggested that repeated Mch challenge causes the maintenance of
      glandular secretion while stopping albumin permeability, that with pre
      administration of alpha-agonists glandular secretion increases, and that pre
      administration of beta-agonists inhibits glandular secretion. When both alpha-
      and beta-agonists are given before the challenge, however, there is no increase
      in vascular permeability.

PMID- 8523168
TI  - [Two cases of sensory neural hearing loss as a manifestation of HIV infection].
AB  - In patients with HIV infection, oral and pharyngeal pathology frequently occurs,
      but there have been no reports on cases of deafness in Japan. Herein, the authors
      report two cases of sensory neural hearing loss in hemophilia A patients infected
      with HIV through factor VIII concentrates. Case 1 was a 16-year-old male with
      hemophilia A. He had been administered factor VIII concentrates starting at 6
      months after birth. At 8 years of age, HIV antibodies were positive. He was
      diagnosed as having AIDS after suffering from pneumocystis carinii. He complained
      of right otalgia and slight vertigo during treatment for a relapse of the
      pneumocystis carinii. He underwent otological examinations at our department. The
      right tympanic membrane showed opacification and serous otorrhea was noted. Acute
      otitis media was diagnosed and tympanotomy was conducted. Afterwards, the right
      tympanic membrane developed a large perforation and sensory neural hearing loss
      occurred. Case 2 was a 49-year-old male with hemophilia A. He had been
      administered factor VIII concentrates from the age of 23 years. At 48 years of
      age, HIV antibodies were positive. The patient complained of sudden deafness in
      the right ear and slight vertigo. He underwent otological examinations at our
      department. The tympanic membrane was normal bilaterally, but sensory neural
      hearing loss was found in the right ear. It was presumed that acute otitis media
      directly involving the inner ear had caused a perceptive disorder in case 1 while
      a pattern of sudden onset of deafness was apparent in case 2.

PMID- 8523169
TI  - [One stage ipsilateral vascular reconstruction of the carotid artery--distal or
      proximal limits at cervical operation].
AB  - Since 1990, in treating 10 cases with head and neck tumors which had invaded the
      carotid artery, the authors have performed vascular reconstruction of the carotid
      artery. The standard surgical procedure is en bloc resection of the tumor and
      carotid artery and one stage ipsilateral vascular reconstruction of the carotid
      artery at cervical operation using a temporary shunt tube. When the tumor is
      located in a distal or proximal cervical portion, craniotomy or thoracotomy is
      needed in addition to the usual surgical procedure. The author classifies one
      stage ipsilateral reconstruction of the carotid artery into four types, depending
      on the anastomotic site, and describes distal or proximal limits of this
      procedure at cervical operation. Type A: Cervical operation after partial
      resection of the carotid wall; Patch angioplasty or simple arteriorrhaphy. Type
      B: Cervical operation after round resection of the carotid wall; Common carotid
      internal carotid artery graft interposition, etc. Type C: Using craniotomy in
      addition to the cervical operation; Common carotid-middle cerebral artery bypass,
      etc. Type D: Using thoracotomy in addition to the cervical operation;
      Transthoracic subclavian-internal carotid artery bypass, etc. The design of the
      operative technique and adjunct enable distal or proximal limits of this
      procedure to be expanded. It is necessary to discuss the limits of this procedure
      in each case. Selecting an adequate surgical procedure based on intraoperative
      findings requires close teamwork with neurosurgeons and thoracic surgeons.

PMID- 8523170
TI  - [Clinical investigation of transcranial magnetic stimulation of the facial nerve-
      an early prognostic diagnosis of patients with peripheral facial palsy and the
      facial nerve magnetic stimulation site].
AB  - To obtain an early prognostic diagnosis of patients with peripheral facial palsy,
      a magnetic stimulator (Dantec Mag 2) was used to directly stimulate the
      intracranial portion of the facial nerve in 15 normal subjects and 108 patients
      with peripheral facial palsy. In normal subjects and patients with facial palsy,
      compound muscle action potentials (CMAPs) of the orbicularis oris muscle elicited
      by transcranial magnetic stimulation were compared with CMAPs elicited by
      electrical stimulation at a peripheral site of the stylomastoid foramen. This
      technique is similar to electroneurography (ENoG) and is regularly used in our
      department. In normal subjects, the latency of magnetically evoked CMAPs was
      longer (1.0ms, SD 0.39ms) than that of CMAPs evoked by electrical stimulation.
      There were two categories of patients; the first group consisted of patients who
      visited our hospital within 2 weeks after palsy onset with a record of
      electrically evoked CMAPs (ENoG) and magnetically evoked CMAPs, the second group
      consisted of all others. The first group was then divided into four subgroups
      based on minimal ENoG values obtained within 2 weeks after the onset of palsy. In
      patients, ENoG values declined until the seventh day after palsy onset, and then
      plateaued. However, the amplitude ratio of magnetically evoked CMAPs between the
      affected side and normal side showed no tendency to deline until the seventh day
      after palsy onset. Thus, whether magnetically evoked CMAPs could be recorded must
      be discussed in relation to the prognosis of facial palsy. The patients in whom
      magnetically evoked CMAPs could be recorded within the seven days after the onset
      of palsy were classified into a group in which the minimal ENoG value was greater
      than 20%. These patients recovered almost 2 months after the onset of palsy, and
      were significantly better than the recovery rates of those patients in whom
      magnetically evoked CMAPs could not be recorded. The site at which the facial
      nerve is magnetically stimulated remains controversial. In patients with
      peripheral facial palsy, recovery of the stapedial reflex, blink reflex and
      magnetically evoked CMAPs were examined to investigate the site of magnetic
      stimulation. From the clinical perspective, the facial nerve is thought to be
      magnetically stimulated near the meatal foramen that Fisch reported the site of
      damage in Bell's palsy. This stimulation site was almost the same point as that
      calculated from the mean latency difference between magnetically evoked CMAPs and
      ENoG in normal controls.

PMID- 8523171
TI  - [A study of audiologic findings in the elderly].
AB  - We divided people more than 65 years of age into groups, by 5- year age
      intervals, and performed hearing tests based on pure tone, speech sound, and
      inner ear and retrocochlear hearing functions. Thus, we studied the mechanism of
      hearing disorder progression with aging in an attempt to identify factors
      involved in decreased speech sound recognition. The following results were
      obtained. 1. The regression coefficient of speech discrimination ability and the
      mean hearing threshold level were greater in the elderly patients than in the
      younger patients with cochlear hearing loss. 2. Abnormal decreases in speech
      discrimination ability evaluated on the basis of the mean hearing threshold level
      occur more frequently with advancing age. 3. The SISI score increased rapidly in
      patients 80 years of age or older. 4. Directional hearing function (interaural
      time difference threshold) varied more markedly with age. 5. Little difference in
      SSB clipping speech articulation was seen among elderly subjects less than 80
      years old, though scores were lower than those of the control group. However, it
      was decreased in patients 80 or more years old. These results show that the
      effect of a raised pure-tone hearing threshold due to decreased inner ear
      function and the effect of recruitment phenomenon on speech hearing were the same
      in patients from 65 to the late 70s; however, the effect of retrocochlear hearing
      loss clearly increased with age. Therefore, we consider patients 80 or more years
      old, to have an impaired inner ear function which is aggravated and that this, in
      association with advanced retrocochlear disturbance, leads to greatly decreased
      speech discrimination ability.

PMID- 8523172
TI  - Pneumocystis carinii pneumonia associated with inhaled corticosteroids in an
      immunocompetent child with asthma.

PMID- 8523173
TI  - Safety of lidocaine-prilocaine cream in the treatment of preterm neonates.
AB  - The safety of lidocaine-prilocaine cream (EMLA) was evaluated in an open trial in
      30 preterm neonates (mean gestational age, 32.8 weeks; birth weight, 1911 gm);
      0.5 gm was applied to the heel for 1 hour. Mean baseline and follow-up (4, 8, or
      12 hours after EMLA application) methemoglobin levels were not different, ranging
      from 1.15% to 1.45%, and from 1.13% to 1.49%, respectively.

PMID- 8523174
TI  - Clinical recognition of occult bacteremia.

PMID- 8523175
TI  - Corticosteroid therapy for Pneumocystis carinii pneumonia.

PMID- 8523176
TI  - Correction: heparin-vancomycin solution to prevent central venous catheter
      infections.

PMID- 8523177
TI  - Insulin resistance and lipid profile in obese adolescents.

PMID- 8523178
TI  - Referral to subspecialists.

PMID- 8523179
TI  - Prenatal diagnosis by analysis of fetal cells in maternal blood.
AB  - The data accumulated thus far indicate that fetal NRBCs are the target cell type
      of choice in maternal blood for most investigators, although some groups continue
      to work with the trophoblast. Reports of persistent circulation of hematopoietic
      stem cells, lymphoid/myeloid progenitors, and lymphocytes mandate that removal of
      these cell types must occur before clinical diagnosis of the current pregnancy
      can be made. In selected cases, accurate detection of fetal aneuploidy has been
      made from fetal cells in maternal blood; the clinical evaluation sponsored by the
      National Institute of Child Health and Human Development will determine the
      sensitivity and specificity of cytogenetic diagnosis in a larger group of
      pregnant women, but this information will not be available for several years. At
      present, detection of uniquely fetal, paternally inherited gene polymorphisms or
      mutations such as the Rh(D) antigen is possible only because the mother lacks
      these genes; hence, maternal cell contamination does not hinder diagnosis.
      Currently the presence of large numbers of maternal cells in enriched samples
      precludes single-gene diagnosis for conditions in which the mother carries a
      mutant gene, because her cells are preferentially amplified and difficult to
      distinguish from those of the fetus. It is likely, however, that as techniques of
      individual fetal cell isolation are perfected, maternal cell contamination will
      no longer be an issue, and the entire fetal genome will become available for
      diagnosis and therapy. Pediatricians need to be aware of the progress of research
      in this field, because fetal cell isolation from maternal blood not only could
      change prenatal diagnosis but would change the amount of genetic information that
      arrives with a newborn infant at birth. The ultimate goal of this work is to
      diagnose noninvasively, in the first trimester, the common fetal aneuploidies and
      single-gene disorders, to permit in utero treatment, or to allow low-risk
      pregnant women carrying an abnormal fetus an opportunity for reproductive choice.

PMID- 8523180
TI  - Guidelines for the use of growth hormone in children with short stature. A report
      by the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine
      Society.
AB  - On the basis of the information currently available, the only conditions in which
      GH therapy appears to be safe and effective in increasing adult height are GH
      deficiency and, likely, Turner syndrome. Therapy with GH also increases the
      growth velocity of children with CRI and may increase adult height, but no long
      term data are available. Encouraging short-term results have been reported in
      patients with a few other conditions, such as patients with glucocorticoid
      induced growth failure, renal transplantation, and Prader-Willi syndrome, but the
      data are limited and no long-term studies have been reported; in many other
      conditions the data are either inconclusive or discouraging. For children in
      these latter groups, GH therapy should be considered investigational and
      undertaken only as part of ethically sound, controlled clinical trials. Knowledge
      concerning the conditions in which GH is safe and effective is a prerequisite to
      making rational decisions concerning its use. However, in deciding whether
      therapy is warranted in an individual child, one must consider other important
      factors. The age and emotional maturity of the child, the family structure and
      dynamics, and even financial considerations may, in some cases, outweigh the
      presence of a GH-responsive condition. Likewise, the child's and the family's
      views about "short" stature and the likely benefits of therapy must be
      considered. Ultimately, a decision concerning the appropriateness of GH therapy
      must be individualized and based on a realistic assessment of its impact on the
      quality of life of the child and future adult.

PMID- 8523181
TI  - Effects of secular trends in obesity on coronary risk factors in children: the
      Bogalusa Heart Study.
AB  - OBJECTIVE: To determine whether a secular trend toward increased weight gain was
      present in children examined 11 years apart in the Bogalusa Heart Study and, if
      present, the association of this trend with the cardiovascular risk status of the
      children. STUDY DESIGN: Two biracial cohorts (approximately 65% white, 35% black)
      were identified. One cohort was examined first in 1973 at 7 to 9 years of age and
      was reexamined in 1981 (n = 417). The second was examined first in 1984 at the
      same age and reexamined in 1992 (n = 235). Measurements made at each assessment
      included age, gender, race, height, weight, blood pressure, and lipoproteins. The
      two cohorts were then compared. RESULTS: The two cohorts were comparable at their
      first assessment. However, at follow-up 8 years later the more recent cohort was
      5 to 7 kg heavier without any difference in linear growth; this increased
      ponderosity was associated with adverse changes in lipids and lipoproteins: the
      high-density lipoprotein-cholesterol concentration was 0.15 to 0.35 mmol/L (6 to
      13 mg/dl) lower, triglyceride values were 0.09 to 0.40 mmol/L (8 to 36 mg/dl)
      higher, and there were small increases in total cholesterol and low-density
      lipoprotein-cholesterol concentrations in white girls. Multivariate analyses
      showed that in the more recent cohort these changes were related more to a change
      in ponderosity than to ponderosity. Although blood pressure was generally lower
      in the recent cohort, increasing ponderosity was associated with higher blood
      pressure. CONCLUSIONS: There is a secular trend toward increased ponderosity in
      children examined in the Bogalusa Heart Study. This trend is associated with
      worsening cardiovascular risk, particularly with regard to lipoproteins.

PMID- 8523182
TI  - Prospective surveillance for otitis media with effusion among black infants in
      group child care.
AB  - OBJECTIVE: To document the prevalence of otitis media with effusion (OME) in 102
      black children observed prospectively between 6 and 24 months of age. METHODS:
      Study children attended nine different center-based child care facilities. Middle
      ear status was assessed by pneumatic otoscopy and tympanometry every 2 weeks.
      RESULTS: All children, except one, had OME during the period of observation. The
      proportion of child-examinations revealing bilateral OME ranged from 76% between
      6 and 12 months of age to 30% between 21 and 24 months of age. Effusions were
      considered purulent in only 13% of examinations revealing middle ear fluid. The
      mean incidence of purulent OME was 2.13 episodes per child per year. Sixty-six
      children had at least 4 months of continuous bilateral OME during the period of
      observation; 57 were followed without placement of tympanostomy tubes. Bilateral
      OME had resolved before the second birthday in 95% of these children, and within
      3 months of achieving the 4-month criterion in 50% of subjects. CONCLUSIONS:
      Persistent bilateral OME occurs commonly between 6 and 18 months of age in
      infants who enter group child care during the first year of life. In this study,
      spontaneous resolution of bilateral effusion by 2 years of age was typical.

PMID- 8523183
TI  - Clinical denouement and mutation analysis of patients with cystic fibrosis
      undergoing liver transplantation for biliary cirrhosis.
AB  - OBJECTIVE: To describe the clinical characteristics of patients with cystic
      fibrosis considered for liver transplantation and the clinical outcome after
      transplantation. METHODS: Patient charts were reviewed. Mutation analysis was
      performed on blood or liver tissue samples with a panel of 17 mutations. RESULTS:
      Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver
      transplantation for biliary cirrhosis. Mean age at transplantation was 12.0 years
      +/- 7.7 years (range, 9 months to 23 years). Preoperatively, seven patients had
      mild to moderate pulmonary dysfunction and one moderate to severe pulmonary
      dysfunction. All patients required pancreatic enzyme replacement, and four
      patients required insulin for diabetes mellitus. The 1-year survival rate was
      75%, with no deaths related to septic events. Mean time of follow-up the six
      operative survivors was 4.1 years +/- 1.9 years. Pulmonary function testing, in
      those serially tested, showed that forced expiratory volume in 1 second was
      maintained or improved and that forced vital capacity improved after
      transplantation. Mutation analysis showed the following genotypes: four patients,
      delta F508/delta F508; one patient, delta F508/N1303K; and three patients, delta
      F508/unknown. CONCLUSIONS: Despite the high risk of transplantation, these
      encouraging results indicate that liver transplantation should be considered for
      patients with cystic fibrosis and complications of end-stage liver disease. We
      could not demonstrate an unusual pattern of CF gene mutations in these patients
      with severe liver disease. It appeared that immunosuppressive agents did not have
      a deleterious effect on pulmonary function.

PMID- 8523184
TI  - Fulminant hepatitis associated with centrilobular hepatic necrosis in young
      children.
AB  - OBJECTIVE: To describe fulminant hepatic failure (FHF) in children in the United
      States with clinical and histopathologic features distinctly different from those
      typical of FHF. PATIENTS: Seven young children were seen in early 1994 with
      encephalopathy, coagulopathy, and elevated aminotransferase levels. Liver failure
      was preceded by a prodromal viral illness that resulted in a period of fasting
      without dehydration. Unlike the majority of children with FHF, these patients had
      serum bilirubin levels < 171 mumol/L (10 mg/dl). All children had received
      therapeutic doses of acetaminophen during the prodromal illness. HISTOPATHOLOGIC
      FINDINGS: Histologic findings included zonal necrosis of hepatocytes in a
      centrilobular distribution, which is characteristic of toxic liver injury but is
      atypical for viral hepatitis and sporadic non-A non-B hepatitis. OUTCOME: Six
      patients recovered spontaneously, and one died of complications of liver failure
      and fungal sepsis. The cause of this disorder remains unknown, but we postulate a
      viral or environmental insult that preferentially damages zone 3 hepatocytes. The
      potential for this injury may have been augmented by ingestion of therapeutic
      doses of acetaminophen while patients were in a fasted state. The prognosis was
      good compared with typical FHF in children and correlated with the degree of
      liver necrosis on histologic examination.

PMID- 8523185
TI  - Association of HLA class I antigen deficiency related to a TAP2 gene mutation
      with familial bronchiectasis.
AB  - Two siblings with pansinusitis, nasal polyps, and bronchiectasis were found to
      have histocompatibility lymphocyte antigen (HLA) class I antigen deficiency
      ("bare lymphocyte syndrome") and dysfunction of natural killer cells. Reduced
      class I cell surface expression resulted from a single mutation in the TAP2 gene,
      which is located in the class II region of the major histocompatibility complex
      and encodes subunit 2 of the class I peptide transporter. The defect was
      transmitted in an autosomal recessive manner. This deficiency did not lead to
      severe viral infections but was apparently associated with susceptibility to
      bacterial infections of the respiratory mucosae. We suggest that class I HLA
      typing should be systematically performed in children with unexplained
      bronchiectasis.

PMID- 8523186
TI  - Effect of transfusion in acute chest syndrome of sickle cell disease.
AB  - OBJECTIVE: To study the effects of transfusion on the clinical course and
      oxygenation indexes of children with sickle cell disease and acute chest
      syndrome. METHODS: During a 2-year period, 36 children with sickle cell disease
      admitted with a total of 40 episodes of acute chest syndrome were examined.
      Patients were given a clinical severity score indicative of the degree of
      respiratory distress. Arterial blood gas values were determined 4 to 24 hours
      before and 12 to 24 hours after transfusion, and indexes of oxygenation were
      calculated; six patients who were not given transfusions also had blood gases
      measured on admission and approximately 24 hours later for comparison. RESULTS:
      Blood transfusion was administered during 27 episodes (67.5%); 20 children
      received a simple packed cell transfusion, four had a partial packed cell
      exchange transfusion, and three had a simple transfusion followed by whole blood
      exchange transfusion because of worsening clinical symptoms. Although there was
      no significant change in oxygenation indexes for the six patients not treated
      with transfusion, there was significant improvement in all indexes after
      transfusion. The transfused group had more severe disease on admission, but there
      was no significant difference in duration of fever, tachypnea, retractions, or
      hospital stay between the transfusion and the nontransfusion groups. CONCLUSION:
      Blood transfusion, even simple transfusion of packed erythrocytes, significantly
      improves oxygenation in children with acute chest syndrome and is a valuable
      adjunct to therapy.

PMID- 8523187
TI  - Home nasal continuous positive airway pressure in infants with sleep-disordered
      breathing.
AB  - OBJECTIVE: To review our experience with home nasal continuous positive airway
      pressure (CPAP) in infants with small upper airways and abnormal breathing during
      sleep. STUDY DESIGN: Seventy-four infants with sleep-disordered breathing and
      narrow upper airways, as identified by nocturnal polygraphic recording and
      endoscopic evaluation, were treated at home with nasal CPAP. Infants with
      craniofacial anomalies and trisomy 21, and infants who had been referred to us as
      having had "apparent life-threatening events," made up the majority of the
      population. Because of the rapid growth of infants, regular follow-up visits were
      scheduled to adjust CPAP and mask size. RESULTS: Seventy-two infants were
      successfully treated at home with nasal CPAP; there were two failures. Follow-up
      lasted from 5 months to 12 years. Compliance was not a problem, but home nasal
      CPAP was prescribed only for infants who lived close to our center and whose
      families and pediatricians were willing to support compliance. COMMENTS: Home
      nasal CPAP requires careful, in-laboratory titration and regular follow-up to
      adjust both pressure and mask size. With the support of families and
      pediatricians, home nasal CPAP can be an effective treatment for infants with
      upper airway respiratory problems during sleep. In many cases, it can provide an
      interim solution, enabling physicians to plan surgery at an appropriate time and
      giving infants time to grow before having to undergo surgical stress.

PMID- 8523188
TI  - IgA nephropathy: long-term prognosis for pediatric patients.
AB  - OBJECTIVE: The determination of the ultimate prognosis for patients with IgA
      nephropathy diagnosed in childhood requires long-term follow-up of identified
      patients. The purpose of this study was to obtain such follow-up for patients
      from two centers where the disease has been diagnosed for more than 20 years.
      METHODS: Clinical data at the apparent onset of symptoms and renal histologic
      data were obtained for 103 patients in whom IgA nephropathy was diagnosed before
      age 18 years. Clinical status at last follow-up was obtained from office records
      or from direct contact with the patient. Predicted kidney survival was determined
      by the Kaplan-Meier method. Follow-up of more than 10 years from the time of
      biopsy was available for 40 of the patients. RESULTS: Fourteen of the patients
      have progressed to end-stage renal disease; three others have progressive chronic
      renal insufficiency as defined by an estimated creatinine clearance of less than
      50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree
      of proteinuria at the time of biopsy were associated with poor outcome. For all
      patients, predicted kidney survival from the time of apparent onset was 94% at 5
      years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical
      onset and gender were not associated with poor outcome, but black race and
      severity of renal histologic findings were. CONCLUSION: With follow-up into
      adulthood, the outcome for pediatric patients with IgA nephropathy appears to be
      as serious as that reported in adult patients. Follow-up of a pediatric patient
      with persistent clinical findings should be maintained after the patient's care
      is transferred to a physician caring for adults.

PMID- 8523189
TI  - Hypercalcemia and nephrocalcinosis in patients with congenital lactase
      deficiency.
AB  - We describe 11 infants with congenital lactase deficiency, whose age at diagnosis
      varied from 6 to 88 days. At the time of admission, 7 of 10 infants had
      hypercalcemia. Five of the seven infants for whom renal ultrasonography was
      performed at the time of diagnosis had medullary nephrocalcinosis. Hypercalcemia
      ceased within a week of the start of a lactose-free diet. At the time of
      reevaluation, at the ages of 2 to 10 years, one of the patients still had
      hypercalciuria and nephrocalcinosis was still present in 3 of 11 patients. The
      mechanism of hypercalcemia is unclear but may be related to metabolic acidosis or
      may be promoted by the lactose effect (i.e., by nonhydrolyzed lactose that has a
      direct enhancing effect on calcium absorption in the ileum).

PMID- 8523190
TI  - Mother-to-child transmission of human T-lymphotropic virus type II.
AB  - OBJECTIVE: To determine the frequency of mother-to-child transmission of human T
      lymphotropic virus type II (HTLV-II) and to explore its association with breast
      feeding. DESIGN: Prospective study of children born to a cohort of HTLV-II
      infected pregnant women and a cross-sectional study of older siblings of these
      children. METHODS: Maternal sera were screened with an HTLV-I enzyme immunoassay
      that detects antibody to both HTLV-I and HTLV-II. Confirmatory serologic testing
      and viral typing were performed by Western blot, radioimmunoprecipitation assay,
      enzyme immunoassay with HTLV type-specific proteins, and polymerase chain
      reaction (PCR) analysis of DNA from peripheral blood mononuclear cells. The
      presence of HTLV was evaluated in children by serial serologic and PCR testing.
      Molecular analysis of PCR products from infected mother-child pairs was performed
      by means of restriction fragment length polymorphism of HTLV-II long-terminal
      repeated sequences. RESULTS: Twenty-nine HTLV-II-infected women were identified,
      and these 29 women had 30 pregnancies during the study. Of 28 live infants born
      to infected women, 19 were examined and none was infected with HTLV-II. Sixteen
      older children less than 10 years of age who were born previously to the infected
      women were also examined; two were infected with HTLV-II. One infected child was
      breast fed for 2 months and the second was not breast fed. The viral patterns of
      restriction fragment length polymorphism in the two infected children were
      distinct, but the viral pattern in each child was identical to that of her
      mother's virus, suggesting mother-to-child transmission. Overall, among examined
      children, 1 of 7 breast-fed children (14%; 95% confidence interval: 0, 40) and 1
      of 28 children who were not breast fed (3.6%; 95% confidence interval: 0, 10)
      were infected with HTLV-II. CONCLUSION: Mother-to-child transmission of HTLV-II
      occurs both with and without breast-feeding and at rates similar to those of HTLV
      I. We believe that this is the first demonstration of mother-to-child
      transmission of HTLV-II in the absence of breast-feeding.

PMID- 8523191
TI  - Long-term survival of patients with argininosuccinate synthetase deficiency.
AB  - OBJECTIVE: To monitor long-term survival and outcome of patients with neonatal
      onset argininosuccinate synthetase deficiency (ASD) who were treated with
      specific therapeutic protocols designed to activate alternative pathways of waste
      nitrogen excretion. DESIGN: Patients for this study included 24 infants born
      before 1990 and rescued from hyperammonemic coma caused by neonatal-onset ASD;
      they were referred to this center for enrollment in ongoing clinical studies of
      sodium benzoate, sodium phenylacetate, and sodium phenylbutyrate. Collaborating
      physicians throughout the United States and Canada provided information on
      survival, intellectual development, intercurrent hyperammonemic episodes, and
      anthropometric and biochemical measurements. RESULTS: The cumulative survival
      rate was 87.5% at 5 years and 72% at 10 years of age. Survivors include 15
      patients currently treated with high doses of sodium phenylbutyrate; two patients
      have withdrawn. Among the treated group, 11 are classified as severely to
      profoundly mentally retarded. The remaining four patients have IQ measurements in
      the borderline to mentally retarded range. All patients have had intercurrent
      hyperammonemic episodes; our data indicate that the frequency of the episodes has
      decreased with implementation of the current protocol. These patients are growth
      retarded, but most have height-for-weight z scores within 2 SD of the mean.
      Laboratory studies of plasma amino acids and of hematopoietic, renal, and hepatic
      function are within normal limits with the exception of slightly elevated serum
      aminotransferase values. CONCLUSION: Our results indicate that these drugs are
      safe and that the current protocol improves survival rates. However, survival is
      accompanied by mental retardation, growth retardation, risk of hyperammonemic
      episodes, and the necessity of lifetime adherence to strict medication and
      dietary management.

PMID- 8523192
TI  - Effect of high-dose tyrosine supplementation on brain function in adults with
      phenylketonuria.
AB  - OBJECTIVES: To characterize abnormalities of brain function in patients with
      phenylketonuria (PKU) who had relaxed or stopped the dietary regimen and to test
      whether oral high-dose tyrosine (Tyr) supplementation has a beneficial effect.
      DESIGN: Comparison with a control group; double-blind, placebo-controlled study
      comprising six test times; crossover treatment groups; oral high-dose Tyr therapy
      (100 mg/kg body weight per day) or placebo administration for 4 weeks. SUBJECTS:
      Twenty-four early-treated patients with PKU aged 20.8 (16 to 25) years; 24
      control subjects. METHODS: Plasma concentrations of phenylalanine and Tyr were
      monitored. Neuropsychologic tasks, visual evoked potentials, and spectral
      analysis of electroencephalographic activity were used to evaluate brain
      function. RESULTS: When patients with PKU were compared with control subjects,
      deficits in certain aspects of brain function were confirmed (i.e., a decreased
      ability to sustain attention, prolonged latencies of visual evoked potential
      peaks N1 and P2, and a reduced amount of fast-wave activity on the
      electroencephalogram). Baseline plasma phenylalanine and Tyr concentrations were
      in the typical range of adult patients with PKU. The plasma Tyr concentration
      increased approximately 200% during Tyr supplementation, but no beneficial
      effects were observed. CONCLUSIONS: High-dose Tyr supplementation cannot be
      recommended as an "alternative" treatment for patients with PKU after relaxation
      or termination of strict dietary adherence.

PMID- 8523193
TI  - Cystic fibrosis liver disease and transplantation.

PMID- 8523194
TI  - Cryptorchidism, pediatricians, and family practitioners: patterns of practice and
      referral.
AB  - A multicenter study was undertaken to study cryptorchidism and the timing of
      orchidopexy. A total of 329 children underwent surgery at a mean age of 4.2
      years; 17% of the surgery was performed between 6 and 12 months of age, 25%
      between 5 and 10 years of age, and 9% during or after puberty. Only 30% of the
      pediatricians and 14% of the family practitioners recommended orchidopexy between
      6 and 12 months of age, and 17% of these referring physicians recommended waiting
      until 3 to 10 years of age. Improved education is needed if current
      recommendations for early orchidopexy are to be achieved.

PMID- 8523195
TI  - Thyroid scintigraphy in children and adolescents with Hashimoto disease.
AB  - Between 1989 and 1994, 58 children and adolescents with Hashimoto thyroiditis
      seen at the Sainte-Justine Hospital had thyroid scintigraphy. Their medical
      records and films were reviewed retrospectively. Eighty-nine percent of the
      patients had a homogeneous distribution of tracer on thyroid scintigraphy, unlike
      the heterogeneous distribution classically reported in adults. In children and
      adolescents, thyroid scintigraphy is not helpful in the diagnosis of typical
      Hashimoto thyroiditis.

PMID- 8523196
TI  - Fecal incontinence after the surgical treatment of Hirschsprung disease.
AB  - We examined 60 children 8.9 years (+/- 2.6 years) after surgical treatment of
      Hirschsprung disease to determine the extent of fecal incontinence. Thirty-two
      children (53%) had significant fecal soiling and 16 (27%) less severe soiling.
      The prevalence of incontinence did not diminish with increasing age.

PMID- 8523197
TI  - Antibody response of pediatric solid organ transplant recipients to immunization
      against influenza virus.
AB  - We studied the immunogenicity of the 1992-1993 trivalent split-virus influenza
      vaccine in pediatric solid organ transplant recipients (PSOTRs) and their healthy
      siblings. One month after immunization, 41 (82%) of 50 subjects achieved
      protective titers of antibodies to influenza A, and 30 (60%) to influenza B,
      rates similar to those in healthy siblings. Achievement and persistence of
      protective titers occurred significantly more often in children with preexisting
      antibody. We recommend annual immunization of PSOTRs, their household contacts,
      and health care workers; immunologically naive PSOTRs may benefit from
      immunization before transplantation.

PMID- 8523198
TI  - Central nervous system disease in a child with primary Sjogren syndrome.
AB  - A 9-year-old girl had hemiparesis, and a diagnosis of primary Sjogren syndrome
      was made. The neurologic dysfunction was multifocal, involving both the brain and
      spinal cord, and was recurrent; the findings mimicked multiple sclerosis.
      Corticosteroid treatment during episodes of acute neurologic dysfunction appeared
      to be beneficial.

PMID- 8523199
TI  - Neonatal screening for cystic fibrosis: a comparison of two strategies for case
      detection in 1.2 million babies.
AB  - OBJECTIVES: To review the overall performance of a neonatal screening program for
      cystic fibrosis (CF) from 1981 to 1994, and to compare two strategies of case
      detection. PROGRAM DESIGN: Initially, immunoreactive trypsin (IRT) was measured
      in dried blood spots, and because of the low sensitivity of this test at days 3
      to 5, a second sample was needed from babies with positive test results. Since
      1993 a positive IRT assay result has been followed by direct gene analysis for
      the common CF mutation, delta F508, with the use of the same sample. Cases with
      false-negative results were actively sought throughout the period. RESULTS: With
      IRT alone, 1,015,000 babies were tested. Of 389 babies with CF, 30 had a clinical
      diagnosis of CF made after a negative screening test result or an administrative
      error. Early diagnosis was achieved in 92%. With the IRT/DNA protocol, 59 of 62
      infants had a positive screening test result (44 were homozygous for delta F508)
      among 189,000 babies tested. Three babies with CF had no copy of this mutation,
      but two were identified early because of meconium ileus. The false-positive rate
      was much greater for IRT alone than for the IRT/DNA test (0.69% vs 0.054%). All
      false-positive cases in the IRT/DNA protocol were, of necessity, CF carriers.
      CONCLUSION: The percentage of babies with CF who had an early diagnosis was
      similar with the two protocols, but we concluded that the advantages of the
      IRT/DNA test for screening, particularly in the avoidance of the need for second
      IRT samples, outweighed the drawback of unwanted carrier detection.

PMID- 8523200
TI  - Time of first stool in premature infants: effect of gestational age and illness
      severity.
AB  - OBJECTIVE: To assess the effect of gestational age and illness severity, and the
      effect of antenatal exposure to magnesium sulfate and glucocorticosteroids, on
      the timing of the first stool in preterm infants. METHODS: Medical records of all
      preterm infants (born at < or = 36 weeks of gestational age) admitted to the
      neonatal intensive care unit at Georgetown University Hospital between April 1993
      and March 1994 were reviewed. We studied the time of the first stool in 221
      infants after removing from the investigation the 45 infants who met the
      exclusion criteria. RESULTS: The median age of the infants at the time of the
      first stool was 18 hours, and 90% of the infants passed stool by 100 hours after
      birth. Both the gestational age and the illness severity, as measured by the
      Score for Neonatal Acute Physiology (SNAP), independently correlated with the
      timing of first stool (r = 0.31 and p < 0.0001 for gestational age; r = 0.33 and
      p < 0.0001 for SNAP). Of the 221 infants, 172 (78%) passed stool before the
      initiation of enteral feeding. Antenatal exposure to magnesium sulfate for
      tocolysis had no effect on the timing of the first stool, whereas infants whose
      mothers received glucocorticosteroids for enhancing fetal lung maturity passed
      their first stool significantly earlier than nonexposed infants of identical
      gestational age (p = 0.005). CONCLUSION: Delayed passage of first stool is a
      function of both illness severity and gestational immaturity. Antenatal
      betamethasone exposure leads to earlier stool passage, whereas antenatal exposure
      to magnesium sulfate does not affect the timing of first stool in premature
      infants.

PMID- 8523201
TI  - Renal handling of carnitine in ill preterm and term neonates.
AB  - OBJECTIVE: To investigate the renal handling of carnitine in preterm and term ill
      neonates. METHODS: We studied the fractional tubular reabsorption of carnitine
      and the proximal renal tubular function of infants in the first week of life who
      were receiving very little or no carnitine in their diets. RESULTS: Mean plasma
      levels were low: total carnitine was 16.4 +/- 7.0 mumol/L, free carnitine was 9.2
      +/- 5.0 mumol/L, and acylcarnitine was 7.2 +/- 4.1 mumol/L. The most premature
      group of neonates (gestation age, 26 to 31 weeks) had a fractional tubular
      reabsorption rate of free carnitine of 94.3% +/- 3.3%, which was lower than in
      the other two groups (98.1% +/- 2.4% for gestational age 32 to 36 weeks, p =
      0.001; and 99.2% +/- 0.6% for gestational age 37 to 42 weeks, p = 0.002). In all
      patients the fractional tubular reabsorption of acylcarnitine was lower than that
      of free carnitine, indicating possible tubular secretion of acylcarnitine. It
      correlated with the total plasma carnitine levels (r = 0.53; p = 0.002). The
      fractional tubular reabsorption of free carnitine also correlated with
      gestational age (r = 0.60; p < 0.001). CONCLUSIONS: Ill neonates have a
      fractional tubular reabsorption rate of free carnitine within the normal range.
      It increases with gestational age, and has the same maturation rate as the other
      known indexes of proximal tubular function.

PMID- 8523202
TI  - Familial pulmonary lymphatic hypoplasia associated with fetal pleural effusions.
AB  - Two siblings born with pleural effusions died of pulmonary insufficiency. The
      infant born with fetal hydrops at 30 weeks of gestational age lived 45 minutes.
      The lung weights were mildly hypoplastic on postmortem examination. The sibling,
      born at 37 weeks of gestational age lived 8 days. Postmortem lung weights were
      normal, but the infant had a congenital heart anomaly consisting of a complicated
      vascular ring. Morphometric analysis of both infants indicated relatively normal
      lungs except for interlobular septal lymphatic hypoplasia, apparently a specific,
      previously unrecognized cause of fetal pleural effusions.

PMID- 8523203
TI  - Oxygen cost of breathing in newborn infants with long-term ventilatory support.
AB  - Oxygen consumption (VO2) was measured during controlled and spontaneous
      ventilation with continuous positive airway pressure in newborn infants in whom
      chronic lung disease later developed. The oxygen cost of breathing (the
      difference in VO2 between spontaneous and controlled ventilation) was
      significantly higher in infants with chronic lung disease than in control infants
      (20.1% +/- 7.5% and 4.8% +/- 4.9% of VO2 during spontaneous ventilation (p <
      0.05), respectively).

PMID- 8523204
TI  - Congenital streptococcal toxic shock syndrome with absence of antibodies against
      streptococcal pyrogenic exotoxins.
AB  - Congenital infection with group A beta-hemolytic streptococcus was complicated by
      toxic shock syndrome in a neonate. We hypothesize that the severity of the
      clinical syndrome was related to the streptococcal pyrogenic exotoxin in the
      absence of corresponding antibodies. The outcome may have been favorably
      influenced by the antibodies to streptococcal pyrogenic exotoxin present in the
      immunoglobulins given as treatment.

PMID- 8523205
TI  - Lamotrigine for the treatment of epilepsy in childhood.
AB  - OBJECTIVE: In this multicenter study, the efficacy and tolerability of
      lamotrigine were assessed in 285 children less than 13 years of age, recruited
      from 37 centers in 11 countries. METHODS: Pooled data from five open add-on
      studies have been analyzed. All the children had treatment-resistant epilepsy and
      most had two or more seizure types. Seizure frequency and global evaluation were
      assessed at the end of four successive 12-week periods of therapy. RESULTS:
      Seizure frequency was reduced by 50% or more in one third of the patients.
      Lamotrigine was effective in all seizure types examined, particularly for typical
      and atypical absence seizures. Atonic seizures also responded well. Improvement
      was well maintained during the treatment period. The maintenance dose had to be
      adjusted according to concomitant medication; dose ranges were 1 to 5 mg/kg per
      day for children taking valproate and 5 to 15 mg/kg per day for those not taking
      valproate. The commonest reported adverse experiences were somnolence, rash,
      vomiting, and seizure exacerbations. Adverse experiences led to withdrawal of
      treatment from 36 patients (12.6%). CONCLUSIONS: These results indicate that
      lamotrigine is well tolerated and is effective for a broad range of seizure
      types, especially absence seizures and atonic seizures.

PMID- 8523206
TI  - Acute interstitial nephritis associated with loracarbef therapy.
AB  - We describe a biopsy-confirmed case of acute interstitial nephritis associated
      with the use of loracarbef in an 18-month-old boy, which resulted in end-stage
      renal failure. This complication has been documented with the use of beta-lactam
      antibiotics, and it seems likely the loracarbef was responsible for acute
      interstitial nephritis in this patient.

PMID- 8523207
TI  - Aminosalicylates for the treatment of inflammatory bowel disease.

PMID- 8523208
TI  - Statement of the North American Society for Pediatric Gastroenterology and
      Nutrition (NASPGN). Indications for pediatric esophageal pH monitoring.

PMID- 8523209
TI  - Helicobacter pylori-associated gastroduodenal disease in symptomatic Chilean
      children: diagnostic value of serological assay.
AB  - A newly developed enzyme-linked immunosorbent assay (ELISA) IgG serological assay
      for the diagnosis of Helicobacter pylori infection was used recently in two
      epidemiological surveys in Chile. To evaluate the diagnostic efficacy of this
      assay in a local symptomatic pediatric population, we studied 70 school-age
      patients referred for upper gastrointestinal endoscopy because of complaints
      suggestive of gastroduodenal disease. Evidence for antral H. pylori infection was
      sought by three biopsy-related methods: culture, histology, and urease activity.
      IgG anti-H. pylori serum antibodies were determined by ELISA. Altogether, chronic
      antral gastritis was found in 55 patients and duodenal ulcers in nine; 11
      subjects had normal histology. Sixty (86%) patients had H. pylori in the antrum.
      This group had significantly higher mean IgG optical density values when compared
      with the H. pylori-negative group (1.860 versus 0.669; p < 0.001). The
      sensitivity and specificity of the assay in detecting antral H. pylori were both
      90%; the positive predictive value was 98% and the negative, 60%. Accuracy of the
      assay was superior in predicting the presence or absence of gastroduodenal
      lesions with a sensitivity of 96%, a specificity of 92%, a positive predictive
      value of 98%, and a negative predictive value of 86%. We conclude that the
      diagnostic efficiency of this assay renders it appropriate both to screen for H.
      pylori-associated gastroduodenal disease in individual patients and to be used in
      seroepidemiological surveys.

PMID- 8523210
TI  - Intestinal mucin inhibits adhesion of human enteropathogenic Escherichia coli to
      HEp-2 cells.
AB  - Mucins are complex glycoproteins that cover the intestinal mucosal surface and
      are thought to provide protection against enteropathogenic infections by
      preventing bacterial adherence and subsequent colonization, invasion and toxin
      delivery. The aims of this study was to evaluate the capacity of intestinal mucin
      to inhibit epithelial cell adhesion by human enteropathogenic Escherichia colI
      (EPEC). EPEC strain E2348/69 (serotype O127:H6), known to produce a 94-kd
      epithelia cell-adhesion-mediating outer membrane protein called intimin and known
      to contain an EPEC adherence factor (EAF) plasmid, and three of its mutants were
      studied. Crude mucus was obtained from rabbit small-ubtestinal mucosal scrapings.
      Purified mucins were isolated by serial cesium chloride density gradient
      ultracentrifugation. Bacterial adhesion to HEp-2 epithelial cell monolayers in
      the presence of purified intestinal mucins was quantified by recovery of live
      viable bacteria as colony-forming units. EPEC strain E2348/69 adhesion was
      inhibited in a concentration-dependent manner by increasing amounts of mucin
      (adhesion suppressed to <1% by 150 microgram mucin). The relative magnitudes of
      inhibition of adhesion of E2348/69 and its mutants [JPN15 (EAF plasmid negative),
      JPN15.96(pMAR7) (intimin negative), and JPN15.96 (intimin negative, EAF plasmid
      negative)] were similar in the presence of equal amounts of mucin. The presence
      of the intimin protein and EAF plasmid are not necessary to the proficiency of
      mucin to inhibit HEp-2 epithelial cell adhesion.

PMID- 8523211
TI  - Identification of a marker antigen for the endocytic stage of intestinal
      development in rat, sheep, and human.
AB  - Vacuolated enterocytes are highly endocytic epithelial cells present in
      intestines of diverse mammalian species during neonatal and/or fetal development.
      Using monoclonal antibodies raised against membrane fractions, we previously
      identified a 55-61 kd membrane glycoprotein that is restricted to apical
      endosomal tubules of vacuolated enterocytes in fetal and suckling rats. To
      determine whether this cell-specific antigen is present in vacuolated enterocytes
      of fetal sheep or humans, the endosomal antigen was immuno-affinity purifed from
      rats and used to generate and purify specific rabbit polyclonal antibodies. Light
      microcopic and electron microscopic immunocytochemistry showed that antigens
      cross-reactive with the rat endosomal antigen are present in vacuolated
      enterocytes of fetal sheep and fetal human small intestine and are restricted to
      apical endosomal tubules in these cells. Immunoblot analysis of tissue extracts
      from fetal human intestines showed antigen(s) at 55 and 60 kd, as well as a major
      form at 130 kd. Cross-reactive antigen(s) from fetal sheep intestines appeared as
      42- and 50-kd bands. Although the molecular identities of the sheep and human
      antigens are not yet established, these results show that these antigens can
      serve as markers for the endocytic state of intestinal developmemt in humans as
      well as other mammals.

PMID- 8523212
TI  - Human milk kappa-casein and inhibition of Helicobacter pylori adhesion to human
      gastric mucosa.
AB  - Readily digested caseins, which account for almost half of the protein content in
      human milk, are important as nutritional protein for breast-fed infants. It has
      also been advocated that part of the antimicrobial activity of human milk resides
      in the caseins, most likely the glycosyated K-casein. Top explore this
      possibility, we purified K-casein from human milk to homogeneity by a two-step
      size-exclusion chromatography procedure. Purified human K-casein, in contrast to
      K-casein purified from bovine milk, effectively inhibited the cell lineage
      specific adhesion of fluoroisothiocyanate-labeled Helicobacter pylori to human
      gastric surface mucous cells. The inhibitory activity was abolished by
      metaperiodate oxidation and considerably reduced by preincubation with alpha-L
      fucosidase but not with alpha-N-acetylneuraminidase or endo-beta-galactosidase.
      These results strongly support the view that fucose containing carbohydrate
      moieties of human K-casein are important for inhibition of H. pylori adhesion
      and, thus, infection. They also suggest that breastfeeding may protect from
      infection by H. pylori during early life and that species-specific glycosylation
      patterns, as illustrated by human bovine K-casein, partly determine both the
      narrow host spectrum of this human gastric pathogen and the capacity to resist
      infection.

PMID- 8523213
TI  - Effects of dietary supplementation with fructooligosaccharides on colonic
      microbiota populations and epithelial cell proliferation in neonatal pigs.
AB  - Two experiments were conducted with neonatal pigs to determine the effects of
      feeding fructooligosaccharides on cecal and colonic microbiota, proliferation of
      cecal and colonic epithelial mucosa, and short-chain fatty acid concentrations in
      the cecum. Experiment 1 consisted of feeding neonatal pigs diets containing
      either 0 or 3 g fructooligosaccharies/L of formula for 15 days and then examining
      the large intestine for changes in cecal and proximal colonic microbiota; cecal
      pH; short-chain fatty acid concentrations; morphology of cecal, proximal, and
      distal colonic epithelial mucosa; gross necropsy; and histopathology.
      Supplementation with fructooligosacchariudes (FOS) did not alter cell counts of
      viable bifidobacterial organisms or total anaerobic microbiota, cecal pH, or
      concentrations of short-chain fatty acids. Cecal mucosal cell density and labeled
      cells increased with FOS consumption. Proximal colonic mucosal crypt height,
      leading edge, labeled cells, proliferation zone, and labeling index increased
      with FOS consumption. Distal colonic mucosal crypt height, leading edge, cell
      density, labeling index, and labeled cells increased with FOS consumption. Gross
      necropsy and histopathology found no significan lesions. In Experiment 2,
      neonatal pigs were fed diets containing either 0 or 3 g fructooligosaccharides/L
      of formula for 6 days. Fecal samples were collected on the first full day of
      feeding and on days 3 and 6 after initiation of feeding. On days 1 and 3,
      concentrations of bifidobacteria were similar between diets; however, on day 6,
      pigs consuming FOS tended to have greater numbers of bifidobacteria (p = 0.08).
      These data suggest dietary consumption of FOS will enhance bifidobacteria
      populations and prevent colonic epithelial mucosa atrophy in neonates fed an
      elemental diet.

PMID- 8523214
TI  - The association of syndromic paucity of the interlobular bile ducts and
      congenital mechanical obstruction of the small intestine.
AB  - Three patients with congenital mechanical intestinal obstruction and features of
      syndromic paucity of the interlobular bile ducts (SPILBD) are presented. Two of
      them have siblings with syndromic paucity of the interlobular bile ducts. Two
      patients had jejunoileal atresia, while the other had a meconium plug with
      intestinal perforation. All subjects underwent surgery for intestinal obstruction
      within the first 24 h of life. Progressive disappearance of the bile ductules was
      observed in one case. We believe that an insult such as vascular insufficiency to
      both bile ductal epithelium and the small intestine may be the cause of this
      congenital disorder.

PMID- 8523215
TI  - Burkitt-type intestinal lymphoma in a child with celiac disease.

PMID- 8523216
TI  - Familial occurrence of cavernous transformation of the portal vein.

PMID- 8523217
TI  - Urinary tract infections and cholelithiasis in early childhood.

PMID- 8523218
TI  - Energy expenditure in congenital heart disease.

PMID- 8523219
TI  - Penoplasty for buried penis.
AB  - Buried penis is a congenitally abnormal arrangement of the foreskin relative to
      the penile shaft, which results in a pseudomicropenis in an otherwise healthy,
      nonobese child. The author proposes a penoplasty technique appropriate for
      correction of this disorder, based on experience with 21 patients.

PMID- 8523220
TI  - Prenatal diagnosis of esophageal atresia.
AB  - The prenatal sonographic detection of esophageal atresia (EA) has been possible
      for more than a decade and relies on the finding of a small or absent fetal
      stomach bubble associated with maternal polyhydramnios. The aims of this study
      were to assess the accuracy of this technique and to determine whether the
      outcome of prenatally diagnosed EA differs from its postnatal counterpart. All
      fetal sonograms performed between January 1989 and October 1993 demonstrating a
      small or absent fetal gastric bubble were reviewed together with all neonates
      with EA treated during the same period. Eighty-seven fetuses with a small (n =
      53) or absent stomach bubble (n = 34) were identified, representing 1.4% of all
      fetal sonographic surveys. Esophageal atresia was present in 15; in 13 of these,
      the maternal amniotic fluid volume was increased. The positive predictive value
      of an absent stomach bubble and polyhydramnios was 56%, and the sensitivity of
      prenatal sonography in the diagnosis of EA was 42%. One neonate with EA had the
      prenatal diagnosis established at another institution, yielding a total of 16
      cases of prenatally diagnosed EA for analysis. Seven (44%) of these had trisomy
      18. Of the remaining nine, two had isolated EA, two had laryngeal atresia and EA,
      and there were two late-gestational unexplained fetal deaths. Only four (25%)
      survived through the neonatal period. The prognosis of the fetus with EA is
      radically different from that of the neonate with EA.

PMID- 8523221
TI  - Fetal diaphragmatic hernia without visceral herniation.
AB  - Many cases of congenital diaphragmatic hernia (CDH) are currently detected before
      birth. The authors hypothesized that there is a subgroup of patients with CDH who
      have no evidence of visceral herniation in utero and who would be expected to
      have less pulmonary hypoplasia and a good prognosis. Among 41 neonates with left
      sided CDH treated between January 1990 and October 1993, 17 cases were diagnosed
      after birth. Ten of the 17 had undergone detailed fetal sonographic imaging at or
      after 20 weeks' gestation. After independent review of the prenatal scans of
      these 10 patients, one was found to have evidence of a diaphragmatic hernia and
      was excluded from further analysis. The other nine fetuses survived, and
      prosthetic repair of the diaphragmatic defect and extracorporeal membrane
      oxygenation (ECMO) were each required in only one patient. This contrasted with
      the outcome for 18 control patients with prenatally diagnosed CDH: 4 (22%) died,
      13 (72%) required prosthetic repair, 9 (50%) were supported with ECMO and the
      duration of ventilatory support and hospital stay were significantly longer.
      There is a spectrum of severity among both pre and postnatally diagnosed cases of
      CDH. In the neonate with an isolated left-sided diaphragmatic hernia, a good
      prognosis is to be expected if the condition was not detectable by detailed
      prenatal sonography in the second half of pregnancy.

PMID- 8523222
TI  - Duplications of the alimentary tract in infants and children.
AB  - Duplications of the alimentary tract are rare congenital anomalies that could
      present a diagnostic as well as therapeutic challenge. Twenty-seven patients with
      duplications of the alimentary tract were treated at Childrens Hospital Los
      Angeles between 1961 and 1992. Ages ranged from a few days to 5 years (67%
      younger than 1 year). The most common symptoms were nausea and vomiting, and the
      most common sign was a palpable abdominal mass. Three patients presented with
      gastric duplication, which was excised. The majority of the duplications were in
      the jejunum and ileum. All patients except one had primary resection of the
      duplication. One patient with a 45-cm tubular jejunal duplication was treated
      with mucosal stripping of the duplication. Five patients had cecal duplication,
      three patients presented with melena because of ectopic gastric tissue in the
      duplication, and two presented with intestinal obstruction. One of the latter
      patients presented with intussusception with cecal duplication as the leading
      point. Three patients with colonic duplication presented with abdominal pain and
      vomiting leading to excision of the duplication. Of the five patients with rectal
      duplication, three presented with chronic constipation. The other two patients
      presented elsewhere with perianal swelling, which eventually was drained because
      of a mistaken diagnosis of perianal abscess. Subsequently, these two patients
      came to us with persistent perineal fistula. In all our patients, rectal
      duplications were removed through a sacroperineal incision. The only patient in
      this series who died was a 6-week-old boy with gastric duplication; his death was
      attributed to an associated severe cardiac lesion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523223
TI  - Diagnostic pneumoperitoneum accurately predicts the presence of patent processus
      vaginalis.
AB  - Ninety-four infants with unilateral indirect inguinal hernia underwent repair and
      diagnostic pneumoperitoneum (DPP). Contralateral groin exploration was performed
      in all patients including those with a negative DPP result. Thirty-seven (39%) of
      the 94 patients had a positive DPP result, and 36 of 37 (97%) had a patent
      processus vaginalis (PPV) on the side contralateral to the clinical hernia. Fifty
      seven (61%) of the 94 patients had a negative DPP result, and 54 (95%) of these
      had no PPV. Female patients had a 1:1 correlation between DPP and PPV. DPP can
      predict the presence of PPV in the contralateral groin of patients with
      unilateral hernia with precision and minimizes the need for diagnostic groin
      exploration.

PMID- 8523224
TI  - Surgical treatment of intersex disorders.
AB  - Despite the progress made in understanding the factors regulating sexual
      differentiation, infants born with ambiguous genitalia face significant problems.
      The authors reviewed a group of 84 children with ambiguous genitalia managed
      surgically between 1986 and 1993. The most frequent condition was male
      pseudohermaphroditism (PM) (58%); 31% had female pseudohermaphroditism. Fifty
      seven percent of patients were raised as males and 43% as females. In each group
      of patients, feminine and masculine reconstructive operations were performed. In
      only 31% of PM and 60% of PF cases was the diagnosis made within the first 2
      months of life. In 41% of PF and 40% of PM patients, treatment was begun before
      the second year of life, which we consider an acceptable time. The timing and
      type of vaginoplasty were determined by the point of entry of the vagina into the
      urogenital sinus. Of the 29 patients reared as females, 22 required perineal
      vaginoplasty, had pull-through vaginoplasty, and 2 had colovaginoplasty. Since
      1986, we have applied Mollard's clitoroplasty, which preserves the neurovascular
      bundle and is important for experiencing orgasm. Seventeen percent of patients
      with feminization procedures experienced complications. The optimal time for
      masculinization procedures is 2 years of age, after obligatory testosterone
      treatment. If there is utriculus prostaticus (UP) type II or III, it is removed
      before urethroplasty. This is not done for UP types 0 and 1. In PM cases, the
      number of feminization and masculinization operations was 2.1 and 4.05 per
      patient, respectively. It is easier to make a vagina than a phallus, not taking
      into consideration dimensions, aesthetics, or capability of erection of the
      phallus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523225
TI  - Bleomycin therapy for cystic hygroma.
AB  - Intralesional bleomycin injection was used as sclerosant therapy for sixteen
      patients with cystic hygroma. An excellent (complete clinical resolution)
      response was obtained in seven (44%) patients, a good (> 50% response) result in
      seven (44%), and a poor or no response in two (12%). Minor transient side effects
      (fever, vomiting, cellulitis, skin discoloration) were seen in six patients, and
      there were no serious side effects. The results suggest that bleomycin
      intralesional sclerosant is effective therapy for cystic hygroma, with response
      rates comparable to those of surgical removal, but with the advantage of avoiding
      inadvertent nerve damage and scarring.

PMID- 8523226
TI  - Prenatally diagnosed choledochal cysts: observation or early surgery?
AB  - The incidence of subhepatic cysts later confirmed as choledochal cyst has changed
      with the use of prenatal ultrasonography. A new group has emerged: the neonatal
      patient with an antenatal diagnosis. Optimal timing for cyst excision depends on
      variables such as gestational age, weight, associated conditions, biochemical
      liver alterations, development of complications, and the sonographic surveillance
      of size. The author's experience (1992) with an antenatally diagnosed choledochal
      cyst prompted this literature review. The present case showed an abnormal
      choledochopancreatic ductal junction, high amylase content, and a linear pattern
      of growth over time (2 mm/wk). Management consisted of cyst excision and bilio
      enteric reconstruction. Fourteen cases (including the present one) have been
      reported in the world literature. All were females. Seventy-two percent of the
      ultrasound examinations were performed for dating purposes. Subhepatic cysts were
      identified at a mean gestational age of 26.9 weeks (range, 15 to 37 weeks).
      Excision and bilio-enteric reconstruction were performed at a mean age of 45 days
      (range, 9 hours to 6 months). Clinically, 50% of the babies were anicteric, 43%
      were jaundiced, and 7% had a palpable mass. Evidence of cyst growth was present
      in 56% of cases, and 60% had liver fibrosis that reverted to normal. The
      indications for surgery were jaundice (43%), cyst growth (21%), delayed HIDA
      excretion (7%), and elective (29%). Recommendations for managing the
      asymptomatic, anicteric neonate are discussed, entailing a rational approach
      based on growth potential, biochemical liver alterations, and the development of
      obstructive jaundice.

PMID- 8523227
TI  - Preserved viability of the isolated bowel segment, created by omentoenteropexy: a
      histological observation.
AB  - Creation of the isolated bowel segment (IBS) by omentoenteropexy in rats and dogs
      consists of a two-step procedure: initial omentoenteropexy to the antimesenteric
      border of a jejunal segment, and division of its mesentery 6 weeks later.
      Viability of this IBS is maintained by the angiogenic process, which occurs at
      the level of the myoenteropexy. Histological studies were performed by light
      microscopy on the bowel wall structures of the IBS before and after the
      mesenteric division, as well as after a lengthening procedure performed on the
      IBS in one dog. The authors conclude that (1) in rats and dogs the intestinal
      wall structures of all IBS variants created by omentoenteropexy appear close to
      normal, and (2) neovascularization can be clearly detected at the level of the
      omentoenteropexy.

PMID- 8523228
TI  - A new technique for laparoscopic repair of hypertrophic pyloric stenosis.
AB  - Since 1987, pyloric traumamyoplasty, a technique for the resolution of
      hypertrophic pyloric stenosis, has been used in 111 patients. Continuous prensile
      force is applied with Babcock intestinal clamps, with consequent rupture of the
      muscular layer, without disruption of the mucosa. Because this is a simple
      procedure that requires introduction of only one noncutting instrument, it has
      now been applied laparoscopically in 17 patients. Twelve were under 30 days of
      age; seven weighed less than 3.5 kg. The hospital stay averaged 1.8 days, and the
      average surgical time was less than 30 minutes. Only two trocar incisions were
      made in each case--one for the laparoscope video camera and lamp, the other for a
      modified Babcock clamp. There were no deaths and no complications related to the
      pyloric repair procedure. The authors conclude that laparoscopic pyloric
      traumamyoplasty is an attractive alternative for the management of hypertrophic
      pyloric stenosis.

PMID- 8523229
TI  - Immunohistochemical study of proliferating cell nuclear antigen in hepatocytes of
      biliary atresia: a parameter to predict clinical outcome.
AB  - The hepatic lobulus was studied histologically and immunohistochemically using
      the monoclonal antibody for proliferating cell nuclear antigen (PCNA/Cyclin, a
      cell-cycle-related nuclear protein) in 27 patients with biliary atresia (BA) and
      six normal infants. The study showed that the labeling index (LI) for PCNA
      positive hepatocytes was 37.21 +/- 17.75% in the patients with BA and 3.14 +/-
      1.5% in the normal infants (P < .0001). LI for PCNA-positive cells was higher in
      the periportal area than the pericentral area (P < .01). LI was not related to
      the patients' age at the time of hepatic portoenterostomy. LI was 20.80 +/- 7.03%
      for patients whose jaundice cleared postoperatively and 48.49 +/- 13.43% for
      patients who had persistent jaundice (P < .001). Conventional histological
      studies of the same specimens showed common findings of BA, such as
      hepatocellular degeneration, necrosis, inflammatory cell infiltration, and giant
      cell transformation. Most patients with BA had 8.94 +/- 13.55% giant cell
      transformation among 1,000 hepatocytes. Patients who exhibited high giant cell
      transformation had an unfavorable outcome. Only 0.42% of giant cells were
      immunoreactive for PCNA. In conclusion, the PCNA expression of hepatocytes is
      closely related to the prognosis of patients with BA, and thus could be used as a
      prognostic indicator.

PMID- 8523230
TI  - Collagen-coated Vicryl mesh: a new bioprosthesis in pediatric surgical practice.
AB  - Collagen-coated Vicryl mesh (C.C.V.M.) was used in 28 children who needed repair
      of thoracic and abdominal wall defects. Herein the authors report the clinical
      experience, surgical technique, and outcome in these cases.

PMID- 8523231
TI  - Intraoperative identification of parathyroid gland pathology: a new approach.
AB  - Technetium 99m-sestamibi, a radiopharmaceutical used for the diagnostic imaging
      of abnormal parathyroid tissue, and the Neoprobe 1000, a hand-held, gamma
      detecting probe, were used concurrently, during surgical exploration, in three
      children with hyperparathyroidism. This novel combination assisted with the
      identification of an ectopic mediastinal parathyroid adenoma and with the
      localization of multiple hyperplastic parathyroid glands. 99mTc-sestamibi
      combined with the Neoprobe 1000 may prove to be a useful adjunctive technique for
      the intraoperative localization of abnormal parathyroid tissue in selected
      patients.

PMID- 8523232
TI  - Does research during general surgery residency correlate with academic pursuits
      after pediatric surgery residency?
AB  - A study was designed to evaluate whether successful candidates in pediatric
      surgery have performed laboratory research with publication, and if such
      preparation leads to continued investigations. We requested a curriculum vitae
      from the 248 pediatric surgeons who began their pediatric surgery residencies
      (PSR) between 1979 and 1992. For nonresponders, data were collected from
      physician directories. Indicators of academic status, personal information, and
      publication data were obtained. Responders had more publications before, during,
      and after PSR. Those who published during general surgery residency (GSR) had
      more research years during their residency. Among responders, 59% had spent time
      in the laboratory, and the percentage with laboratory time increased over the
      study period. Those with laboratory experience had more laboratory and clinical
      papers before PSR. Ninety-four percent were from university-based GSRs and 6%
      were from community GSRs. University general surgery residents did not have more
      publications during GSR or PSR but had a greater number of publications after
      PSR. University general surgery residents had more laboratory publications during
      GSR and after PSR, but did not have more clinical publications. Publications
      during GSR and after PSR increased during the study period, but not during PSR.
      Time in the laboratory during GSR did not independently predict continued
      laboratory research. Those with laboratory papers during GSR did not publish more
      basic science papers after PSR. Several surgeons had basic science publications
      that were initiated only after their PSR. In a recent study that compared
      successful and unsuccessful PSR candidates, the successful candidates were found
      to have more publications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523233
TI  - Intestinal perforations in infants with a very low birth weight: a disease of
      increasing survival?
AB  - Seventeen infants with a very low birth weight (VLBW) and spontaneous, non
      necrotizing enterocolitis (NEC), intestinal perforations are presented; 14 of
      them were seen in the past 3 years. A comparison with 16 surgically treated NEC
      infants (< 1,000 g) is provided. At our institution, the yearly survival of VLBW
      infants increased from 54% to 90% over the past 6 years. All 17 non-NEC patients
      were operated on, and 15 (88.2%) survived. Ileal perforations were observed
      frequently. Initial enterostomies were followed by reanastomosis at an average
      age of 3 months. A 22.6-month follow-up was attained for all survivors. Non-NEC
      intestinal perforations in tiny neonates are increasing and constitute a
      challenging but treatable group. The improving survival rate of VLBW infants will
      probably be accompanied by a variety of complications.

PMID- 8523234
TI  - Failure to detect dopaminergic neuroblastoma in a mass-screening system.
AB  - Dopaminergic neuroblastoma comprised 12% of the patients under 1 year of age, and
      83% of the older ones. Seven cases were missed by the mass-screening system
      performed at age 6 months and were detected after 16 months. Three of these
      advanced cases were positive only for dopamine. These findings supports our
      second mass-screening system using dopamine evaluation at age 14 months.

PMID- 8523235
TI  - Transpubic urethroplasty in children: report of 10 cases with review of the
      literature.
AB  - Posttraumatic prostatomembranous urethral strictures (PUS) in children have
      special features that warrant consideration with respect to management.
      Transpubic urethroplasty (TPUP) was used to treat 10 children who presented with
      posttraumatic PUS. All patients previously had unsuccessful repair attempts with
      other techniques. Urethral stricture was noted in three patients who were cured
      within a few months by urethral dilatations. Appropriate antibiotic therapy was
      begun for prolonged urinary infection in four patients. Complete urinary
      continence was achieved in seven patients (70%), and three (30%) are still
      incontinent. In the latter, the bladder neck and posterior urethra were reported
      to have been damaged seriously, owing to extensive dissections at the time of
      initial treatment. Severe retropubic tissue loss and fibrosis were noted in these
      patients. Thus, the authors emphasize that avoiding further injury to any of the
      continence mechanisms that have survived the injury is as important as performing
      a patent urethral anastomosis. There were no significant complications or
      morbidity associated with TPUP. TPUP provided excellent exposure and
      visualization of the involved anatomy and facilitated accurate suture placement
      and tissue realignment in all patients.

PMID- 8523236
TI  - A new stable isotope tracer technique to assess human neonatal amino acid
      synthesis.
AB  - The amino acid (AA) synthetic ability and requirements of human infants are
      undefined. A stable isotope tracer technique was employed in neonates to assess
      conversion of uniformly labeled 13C glucose into biochemically nonessential AA
      (NEAA). Ten neonates (5 males, 5 females) were studied at a mean age of 7 +/- 2.0
      (SEM) days. The mean gestational age was 35.5 +/- 1.1 weeks, and the mean weight
      at time of study was 2,191 +/- 181 g. Six infants were fed enterally, and four
      received only intravenous 10% dextrose (D10W). Blood samples were obtained
      before, and 30, 60, and 120 minutes after an orogastric bolus of D-[U-13C]glucose
      (100 mg/kg). The conversion of glucose carbon into seven NEAA was assessed by
      measuring their isotopic enrichments in plasma, using gas chromatography/mass
      spectrometry (GC/MS), and was expressed as mole percent excess (MPE), with
      detectable MPE defined as > or = 0.2. The isotopic enrichment of plasma glucose
      also was measured using GC/MS. Free plasma AA concentrations were assayed using
      an automated AA analyzer and expressed in micromoles per liter. The mean glucose
      enrichment was 9.33 +/- 1.8 MPE (range, 5.82 to 13.48). Detectable 13C-labeling
      of the NEAA was observed as follows: Glu in 100% of infants; Gly, 100%; Ala, 90%;
      Ser, 80%; Asp, 70%; Cys, 60%; and Pro, 60%. Detectable Pro enrichment was
      observed in none of three premature infants on D10W. Free plasma Cys
      concentration was markedly lower than normal (19.8 v 86 mumol/L).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8523237
TI  - Gastroesophageal reflux after repair of congenital diaphragmatic hernia.
AB  - Seventy-four survivors of congenital diaphragmatic hernia (CDH) repair were
      reviewed for gastroesophageal reflux (GER). Twenty-nine patients had a prenatal
      diagnosis of CDH, 31 had the diagnosis established during the first 60 minutes of
      life, and 14 had a late diagnosis. Fifty-seven of the 60 patients with a prenatal
      diagnosis or diagnosis at birth had their CDH repaired during the first 24 hours
      of life. Thirty-six of the 37 patients with clinical signs of GER and 10 patients
      without typical clinical signs had documented GER. The overall incidence of GER
      was 62% (46 of 74). The 46 comprised 22 of the 29 patients (75.8%) with a
      prenatal diagnosis of CDH, 21 of the 31 (67.7%) with a diagnosis at birth, and 3
      of the 14 with a late diagnosis. Eleven patients had surgical treatment of GER. A
      significant correlation was found between GER and the preoperative thoracic
      position of the stomach (32 v 8, GER+ v GER-; P < .01) and GER and the prenatal
      diagnosis of CDH (22 v 7, GER+ v GER-; P < .01). Duration of artificial
      ventilation (68.97 +/- 15.33 days v 14.14 +/- 3.89 days, GER+ v GER-; P < .005)
      and duration of hospitalization (22.04 +/- 3.59 weeks v 3.9 +/- 0.88 weeks, GER+
      v GER-; P < .0003) were significantly longer for the patients with pathological
      GER. To decrease the morbidity related to GER, we propose using diaphragmatic
      patches during hernia repair to lower the strain on the crus, and using parietal
      patches to lower intraabdominal pressure after reintroduction of the herniated
      viscera.

PMID- 8523238
TI  - Physical fitness testing in children operated on for tracheoesophageal fistula.
AB  - The maximal physical activity capacity of children operated on for
      tracheoesophageal fistula (TEF) has not been clearly defined. Eight patients
      (average age, 12 years) successfully operated on for TEF at birth underwent
      maximal exercise stress testing on a treadmill, according to the Bruce protocol,
      to test physical work capacity. Heart rate (HR), oxygen consumption (VO2), and
      pulmonary ventilation (VE) were measured by a portable lightweight telemetric
      device. Nine healthy children served as controls. Exercise duration was
      significantly lower for TEF subjects than for controls (11.6 +/- 1.7 minutes v
      15.1 +/- 2.3 minutes; P < .01). Mean HR at rest and during exercise did not
      differ between the groups. All children reached the maximum HR according to their
      age; however, for the majority of TEF patients, this occurred at an earlier stage
      than in the controls. No differences were seen in mean VO2 at rest and on
      exertion between TEF and control children. However, maximal VO2, as measured at
      the end of exercise, was significantly different when normalized per kilogram of
      body weight (VO2/kg = 52.3 +/- 5.8 v 33.3 +/- 6.6; P < .005). The physical
      rehabilitation of TEF children usually takes into account only respiratory and
      nutritional factors. However, complete assessment of their cardiac and
      respiratory function, at rest and on exertion, also should be performed, because
      this may show that some patients have reduced motor performance; evidence is now
      accumulating that these children can safely participate in the same physical
      activities of their healthy peers.

PMID- 8523239
TI  - Bilateral Wilms' tumor: in situ cooling of the kidney facilitates curative
      excision of tumors, with preservation of renal function.
AB  - Bilateral synchronous multifocal Wilms' tumor is a rare malignancy for which no
      optimum treatment has been established thus far. The need to preserve renal
      parenchyma whenever possible is obvious. The authors describe a patient who
      underwent removal of six subcapsular tumors from a kidney that had been protected
      from ischemia by in situ cooling with UW-Belzer solution and by surface cooling.
      This technique was safe, easy to perform, and allowed all the time required to
      resect the tumors under adequate visual control and to wait for analysis of the
      frozen sections. It might be a useful alternative to the more complicated "bench"
      technique.

PMID- 8523240
TI  - A new surgical complication related to corticosteroids in a patient with Henoch
      Schonlein purpura.
AB  - In this case presentation of a 4-year-old boy with histopathologically proven
      Henoch-Schonlein purpura the authors report a surgical complication that occurred
      under corticosteroids; this had not been described previously. Relief of
      abdominal pain was dramatic and the hematemesis disappeared, but an entero
      enteral fistula and abscess developed without any sign of peritonitis. Therefore,
      when corticosteroids are used for symptomatic relief, and intermittent bowel
      obstruction persists during their use, surgical complications should be
      suspected. In such cases, intermittent small bowel obstruction might be the only
      sign of a grave surgical complication.

PMID- 8523241
TI  - Colonic atresia and spinal cord atrophy associated with a case of fetal varicella
      syndrome.

PMID- 8523242
TI  - Torsion of an accessory lobe of the liver in an infant.
AB  - This report concerns a 6-month-old boy who had omphalocele repair as a newborn
      and then had torsion of an accessory hepatic lobe, resulting in necrosis. A
      successful outcome was achieved by resecting the torsed accessory lobe.

PMID- 8523243
TI  - Repair of aortic transection associated with ductal diverticular aneurysm.
AB  - A 14-year-old girl involved in a motor vehicle accident sustained an acute
      traumatic aortic transection at the site of a congenital ductal diverticular
      aneurysm. Aortic transection is a lethal injury that is uncommon in children. A
      ductal diverticular aneurysm is a rare congenital lesion, formed when the ductus
      arteriosus fails to close with aneurysmal formation at the aortic isthmus.
      Diagnosis, management, and pathophysiology of both lesions are discussed.

PMID- 8523244
TI  - Cystic neuroblastoma of infancy.
AB  - Cystic neuroblastoma is exceedingly rare; only 29 cases have been reported in the
      medical literature. The authors treated two children with cystic neuroblastoma.
      The first was a 2-week-old boy with an adrenal lesion; the second was a 15-month
      old girl with solitary thoracic cystic neuroblastoma. Cystic neuroblastoma is
      located, almost exclusively, in the adrenal gland. In contrast to solid
      neuroblastoma, cystic neuroblastoma has a benign course. Cystic neuroblastoma is
      diagnosed earlier than solid neuroblastoma, and the former rarely presents with
      metastatic lesions. All previous reported cases of cystic neuroblastoma were
      diagnosed before 21 months of age. The presence of calcification was rare, and
      only 9.5% had documented elevation of the vanillylmandelic acid or homovanillic
      acid level. Surgical resection of all gross tumor was accomplished in 86% of
      children with cystic neuroblastoma, and in this group none of the patients had
      reported recurrent disease. Both present cases also had surgical resection of the
      entire gross tumor, and likewise have had no evidence of recurrent disease. This
      report brings the total number of reported pediatric cases of cystic
      neuroblastoma to 31; to the authors' knowledge, this is the first report of a
      child with solitary cystic neuroblastoma in an intrathoracic location.

PMID- 8523245
TI  - Male gender assignment in penile agenesis: a case report and review of the
      literature.
AB  - The authors describe a patient with penile agenesis who was reared as a boy and
      died of chronic renal failure. A literature review was performed to clarify the
      management and outcome of patients with aphallia who are raised as males.

PMID- 8523246
TI  - Inverted U-pouch ileal reservoir: a technique for conversion of straight ileoanal
      pull-through.

PMID- 8523247
TI  - Left aortic arch with right descending aorta and right ligamentum arteriosum
      associated with d-TGA and large VSD: surgical treatment of a rare form of
      vascular ring.
AB  - A 1-month-old boy with respiratory distress underwent pulmonary artery banding
      after diagnosis of d-loop transposition of the great arteries and ventricular
      septal defect. Respiratory distress recurred after surgery. Angiography,
      esophagography, and magnetic resonance imaging showed left aortic arch,
      retroesophageal aorta, and right descending aorta. Surgery at 9 months of age
      showed a right-sided ligamentum arteriosum. Division of the ligamentum relieved
      the constriction of the esophagus and trachea caused by this rare form of
      vascular ring.

PMID- 8523248
TI  - Yolk sac tumor in a case of testicular feminization syndrome.
AB  - A 17 month old who had been diagnosed as having testicular feminization syndrome
      (noted during inguinal herniorrhaphy) was operated on because of an abdominal
      mass that had a high serum level of alpha-fetoprotein. Histologically, the lesion
      was a yolk sac tumor. The alpha-fetoprotein level normalized within 2 months of
      the surgery, through the administration of adjunctive chemotherapy containing
      cisplatinum. The patient is disease-free 4 years postoperatively. When performing
      inguinal herniorrhaphy in a girl, the surgeon should be prepared to deal with
      testicular feminization syndrome. If gonadal neoplasm is deniable at the time of
      diagnosis, careful follow-up examinations are needed until completion of the
      development of secondary sex characteristics.

PMID- 8523249
TI  - Axillary breast tissue in an adolescent girl.

PMID- 8523250
TI  - Congenital diaphragmatic hernia and profound prematurity: report of a survivor.
AB  - Congenital diaphragmatic hernia (CDH) continues to be one of the most challenging
      problems in pediatric surgery. The overall mortality rate remains at 40%, and
      death is caused by pulmonary hypoplasia and persistent pulmonary hypertension. It
      has been suggested that in utero repair of the defect should be performed to
      allow the lungs to grow and develop, in the hope of preventing fatal pulmonary
      insufficiency. The authors report the survival of a 960-g premature infant with
      CDH, suggesting that ex utero repair is possible in a very low birth weight
      infant.

PMID- 8523251
TI  - Prune-belly syndrome in a female, complicated by intestinal malrotation after
      successful antenatal treatment of hydrops fetalis.
AB  - The authors report a female case of prune-belly syndrome having an antenatal
      sonographic diagnosis of hydrops fetalis and treated prenatally with
      transplacental digitalis administration. The findings of this case suggest that
      the clinical entity includes various phenotypes or aberrants having different
      origins.

PMID- 8523252
TI  - A case of gastric cicatrization caused by ingestion of sulfuric acid, treated
      with Hunt-Lawrence jejunal pouch substitution for the stomach.
AB  - To the authors' knowledge, there had been no reported pediatric case of total
      cicatrization of the stomach owing to acid ingestion. The authors report a case
      caused by sulfuric acid ingestion. When admitted, the child did not have any oral
      intake and was fed through a jejunostomy, which had been placed in an other
      center. An upper gastrointestinal barium study showed a small gastric fundal
      pouch and no passage to the duodenum, but with passage to the jejunum through two
      fistulas. The modified Hunt-Lawrence pouch was created using the fistulous
      jejunal segment. After 6 months the patient is well.

PMID- 8523253
TI  - Congenital fibrosarcoma masquerading as congenital hemangioma: report of two
      cases.
AB  - The authors report on two infants who had large congenital fibrosarcomas that
      initially were believed to be hemangiomas. Although hemangioma and congenital
      fibrosarcoma can have a similar presentation, their treatment is dissimilar. The
      authors review the anatomic findings, hematologic differences, and radiological
      clues that can help to differentiate congenital fibrosarcoma from congenital
      hemangioma.

PMID- 8523254
TI  - Bilateral abdominoscrotal hydrocele: a case report.
AB  - A 13-month-old boy, who had been diagnosed in utero as having bilateral
      hydroceles, was found to have bilateral abdominoscrotal hydroceles. To date,
      there has been only one previous case of bilateral abdominoscrotal hydroceles in
      an infant. Magnetic resonance imaging was used to make the diagnosis: bilateral
      dumbell shaped fluid filled masses were seen in a coronal image. The patient had
      the abdominoscrotal hydroceles excised through bilateral groin incisions. The
      postoperative course was uneventful, without complication. The etiology and
      diagnosis of abdominoscrotal hydroceles are discussed.

PMID- 8523255
TI  - Preoperative ultrasound diagnosis of a gastric duplication cyst with ectopic
      pancreas in a child.
AB  - Duplication cysts of the antral and duodenal regions are rare, and small ones are
      difficult to diagnose preoperatively. The authors present the case of a 4-year
      old boy with recurrent bouts of upper gastrointestinal hemorrhage over the
      previous 2 years. At first, gastroscopy was diagnostic for antral ulcerations,
      which healed with medical treatment. Chronic blood loss persisted and was
      associated with abdominal pain. A barium study showed antral deformity, with a
      suspected mass, which prompted a selective ultrasound examination, during which a
      1-cm duplication cyst was detected. Of special interest is the change in shape
      and content of that cyst, demonstrated sonographically over a 2-month period. In
      children, high-resolution ultrasonography can be an important step in evaluation
      of the gastrointestinal tract. Here it showed a small but surgically significant
      lesion.

PMID- 8523256
TI  - Solitary intestinal fibromatosis mimicking malabsorption syndromes.
AB  - A 17-month-old baby had symptoms of malabsorption and partial intestinal
      obstruction. These were found to be caused by obliteration of the jejunum by
      solitary intestinal fibromatosis. Solitary intestinal fibromatosis, which may
      imitate malabsorptive diseases of the intestine, is a rare cause of intestinal
      obstruction in the neonatal period and infancy. Diagnostic aids and differential
      diagnosis of this rare disease are discussed, and previously reported cases are
      reviewed.

PMID- 8523257
TI  - Extralobar pulmonary sequestration mimicking cystic adenomatoid malformation in
      prenatal sonographic appearance and histological findings.
AB  - An infant girl with extralobar pulmonary sequestration (PS) composed of
      congenital cystic adenomatoid malformation (CCAM)-like structure is presented.
      Initially, the antenatal sonographic findings indicated CCAM. The macroscopic
      findings of the resected specimen were compatible with extralobar PS; however,
      the microscopic findings showed cystic structure mimicking type II CCAM. The
      combination of PS and CCAM is rare, and it is likely that the embryological
      origin is common to both. There is confusion in the classification of these two
      congenital anomalies. In this report, the histological and sonographic findings
      of PS and CCAM are discussed.

PMID- 8523258
TI  - Exercise-induced QRS changes (Athens QRS score) in patients with coronary artery
      disease: a marker of myocardial ischemia.
AB  - Previous studies have shown a good correlation between exercise-induced changes
      of Q-, R-, and S-waves (Athens QRS score) and the number of the obstructed
      coronary arteries. The present study was undertaken to test the hypothesis that
      abnormal Athens QRS score is related to exercise-induced myocardial ischemia.
      Patients who had exercise radionuclide ventriculography (n = 150) or thallium-201
      scintigraphy (n = 124) within 1 month of cardiac catheterization were studied.
      Athens QRS score was calculated based on the exercise-induced changes of the Q-,
      R-, and S-waves. Changes in Athens QRS score were compared to the number of
      obstructed coronary arteries, segmental contraction abnormalities, and exercise
      induced myocardial perfusion defects. Athens QRS score and coronary artery
      disease: The Athens QRS score was decreased as the number of obstructed coronary
      arteries increased (normal coronary arteries 3.7 mm, confidence interval 1.0 to
      3.9, one vessel disease 1.2 mm, two vessel disease -0.6 mm, three vessel disease 
      1.3 mm, p < 0.001). Athens QRS score and segmental contraction abnormalities: The
      Athens QRS score decreased as the number of segmental contraction abnormalities
      increased (no segmental contraction abnormalities 2.5 mm, confidence interval 1.0
      to 3.9, one segmental contraction abnormality -0.4 mm, two segmental contraction
      abnormalities -1.5 mm, three segmental contraction abnormalities -2.6 mm, p <
      0.001). Athens QRS score and reversible myocardial perfusion defects: The Athens
      QRS score was decreased as the number of exercise-induced myocardial perfusion
      defects increased (no perfusion defect 2.4 mm, confidence interval 0.9 to 3.9,
      one perfusion defect -0.7 mm, two perfusion defects -2.6 mm, three perfusion
      defects -3.3 mm, p < 0.001). Abnormal values of the Athens QRS score were better
      correlated with the number of exercise-induced segmental contraction
      abnormalities or the myocardial perfusion defects than the number of obstructed
      coronary arteries (p < 0.001). Exercise-induced changes in Athens QRS score were
      directly related to the number of obstructed coronary arteries, to exercise
      induced segmental contraction abnormalities and to exercise-induced myocardial
      perfusion defects. However, Athens QRS score changes were more closely related to
      the number of exercise-induced segmental contraction abnormalities or to the
      exercise-induced myocardial perfusion defects than to the number of obstructed
      coronary arteries. The data suggest that exercise-induced QRS changes, Athens QRS
      score are related to exercise-induced myocardial ischemia.

PMID- 8523259
TI  - [Endothelial dysfunction of the infarct-related coronary artery after reperfusion
      therapy].
AB  - The response of the infarct-related coronary artery to acetylcholine (20, 30, 50
      micrograms) was investigated in 30 patients without restenosis during a 4-month
      follow-up period after direct percutaneous transluminal coronary angioplasty
      (PTCA) of the left proximal anterior descending coronary artery. The patients
      were divided into two groups according to wall motion as obtained by the
      centerline method from a left ventricular angiogram: moderate group (n = 10) with
      reduced wall motion with less than 20 abnormal contraction segments (moderate
      reduction at the infarcted site), severe group (n = 20) with reduced wall motion
      with 20 or more abnormal contraction segments (severe reduction). The
      acetylcholine-induced percentage changes in luminal diameter were assessed at the
      PTCA site and the distal portion of the coronary artery and the effect of
      acetylcholine was compared at the two sites. Coronary artery diameter in the
      moderate and severe groups displayed 8.1 +/- 24.9% and 7.4 +/- 30.8% contraction
      at the PTCA site and 38.3 +/- 46.3% and 72.5 +/- 28.2% contraction at the distal
      portion, respectively. Severe group had greater contraction at the distal portion
      than at the PTCA site. Vasoconstriction of the patent infarct-related coronary
      artery tended to occur in the infarcted area where wall motion was severely
      affected. In addition, endothelial dysfunction appears to be induced by a lengthy
      interruption of epicardial coronary blood flow and is present in the patent
      infarcted coronary artery without restenosis.

PMID- 8523260
TI  - [Prognosis of patients with triple vessel disease and old myocardial infarction:
      relationship to the number of total coronary occlusions].
AB  - Patients with myocardial infarction (MI) and triple vessel coronary disease
      generally have poor prognoses. However, it is not known whether there are
      particular angiographic variables associated with the poor prognosis in MI
      patients with triple vessel disease. The angiographic variables for poor
      prognosis were investigated in 43 MI patients with triple vessel disease (32 men
      and 11 women, mean age 63 +/- 9 years) who were followed medically for a mean of
      32 +/- 28 months. There were 13 cardiac deaths (30%) and 10 late-coronary artery
      bypass grafting (23%). Twenty patients were alive and well. The patients who died
      of cardiac causes had lower ejection fractions (42 +/- 18% vs 49 +/- 15%, p <
      0.05), a higher prevalence of two vessel occlusion (77% vs 40%, p < 0.05), and a
      higher prevalence of coronary occlusion opposite the MI site (69% vs 25%, p <
      0.01) when compared to survivors, although there were no significant differences
      in age, MI sites, or the prevalence of occlusion in the infarct-related artery.
      Multivariate analysis with the Cox proportional hazards model revealed that
      coronary occlusion opposite the MI site (hazards ratio 16.36) and an age of > or
      = 65 years (4.46) indicated a significantly high ratio. The hazard ratio of the
      ejection fraction and two vessel coronary occlusion were not significant. The
      poor prognosis of MI patients with triple vessel coronary disease may be related
      to impaired left ventricular function and to coronary occlusion opposite the MI
      site and greater age. This may have important clinical implications in the
      initial decision for interventional therapy.

PMID- 8523261
TI  - [Effect of cilazapril on exercise tolerance and neurohumoral factors in patients
      with asymptomatic chronic heart failure after myocardial infarction].
AB  - The effects of cilazapril on exercise tolerance and neurohumoral factors were
      investigated in old myocardial infarction (OMI) patients with asymptomatic heart
      failure and reduced left ventricular ejection fraction. Cilazapril (0.5 mg) was
      administered once daily to OMI patients (n = 20) [NYHA class I, sinus rhythm,
      ejection fraction by radionuclide scanning < 50% (36.8 +/- 9.1%, mean +/- SD)].
      Two weeks later, five patients were excluded from the study because of cough or
      hypotension, and 15 patients received 1.0 mg cilazapril once daily for the next 6
      weeks. Exercise tolerance, neurohumoral factors and ejection fraction were
      measured in OMI patients before and after administration of cilazapril. Seven age
      matched healthy adults served as the controls. OMI patients had latent heart
      failure because their exercise tolerance values and aldosterone levels were lower
      and alpha-atrial natriuretic polypeptide levels were higher than those in healthy
      subjects. In OMI patients, 8 weeks after cilazapril administration, exercise
      duration increased from 545 +/- 59 to 590 +/- 74 sec (p < 0.05), anaerobic
      threshold from 17.5 +/- 3.2 to 20.1 +/- 2.8 ml/min/kg (p < 0.05), peak-VO2 from
      23.5 +/- 4.7 to 27.1 +/- 4.4 ml/min/kg (p < 0.05), plasma renin activity from
      1.34 +/- 1.13 to 5.82 +/- 5.47 ng/ml/hr (p < 0.01) and alpha-atrial natriuretic
      polypeptide decreased from 100.7 +/- 44.3 to 80.5 +/- 28.0 pg/ml (p < 0.05). In
      patients with asymptomatic left ventricular dysfunction after myocardial
      infarction, 8 week's cilazapril administration improved exercise tolerance and
      neurohumoral conditions.

PMID- 8523262
TI  - [Follow-up study of Takayasu arteritis with aortic regurgitation].
AB  - The clinical courses of patients with Takayasu arteritis vary especially when
      aortic regurgitation is involved. The clinical features and outcomes of Takayasu
      arteritis were studied in 78 patients to clarify the influence of aortic
      regurgitation on the natural history, especially the earlier stages of aortic
      regurgitation after onset of Takayasu arteritis. During the average 12.7-year
      follow-up period, 7% (3/43) of patients without aortic regurgitation died, but
      17% (6/35) of patients with aortic regurgitation died. Mortality was low (6%;
      1/16) in patients with mild (grade II or less) regurgitation, but high (26%;
      5/19) in patients with severe (greater than grade III) regurgitation. Predictors
      indicating patients likely to die of severe aortic regurgitation were age at
      onset (mean age of 30.0 years), C reactive protein and erythrocyte sedimentation
      rate, and presence or absence of involvement of major branches of the aortic
      arch. Mortality was 33% (2/6) in patients without involvement of the major
      branches, which was significantly higher than that of patients with such
      involvement (17%; 2/12). From the initial consultation, most patients with mild
      regurgitation remained stable, but younger patients with severe regurgitation due
      to acute pathological processes of the ascending aorta from the early stage and
      elevated erythrocyte sedimentation rate showed deterioration in their clinical
      courses. Younger patients with elevated erythrocyte sedimentation rate, intact
      major branches of the aortic arch, no signs of classical pulseless disease, and
      severe aortic regurgitation due to Takayasu arteritis have a poor prognosis.

PMID- 8523263
TI  - [A case of aortic bicuspid valvular endocarditis with congenital left ventricular
      diverticulum].
AB  - A 29-year-old man had a prolonged fever and painful Osler's nodes on his right
      foot. The aortic valve was bicuspid with vegetation mass and the left ventricular
      diverticulum was additionally present connecting with the left ventricular
      outflow tract. An operation was performed after intravenous administration of
      antibiotics for 3 weeks. The aortic bicuspid valve and the vegetation were
      removed and replaced by an artificial valve (SJM-HP 19 mm). The left ventricular
      diverticulum was resected. The echocardiographic findings correlated well with
      the intraoperative observation.

PMID- 8523264
TI  - [A quantitative evaluation of coronary steal phenomenon in coronary artery
      pulmonary artery fistula: case report].
AB  - A 67-year-old woman was admitted to our hospital with a complaint of anterior
      chest pain on exertion. Auscultation disclosed a continuous murmur and exercise
      electrocardiography revealed positive ischemic ST change. Coronary angiography
      showed a large left coronary fistula and a small right coronary fistula into the
      main pulmonary artery. To evaluate the influence of the fistula on coronary
      circulation, we measured blood flow in the left anterior descending artery (LAD)
      and in the fistula artery using a 0.014 inch Doppler guide wire. Before surgery,
      blood flow in the LAD decreased during rapid atrial pacing (130 bpm) but that in
      the fistula remained constant. After the surgery, there was no remarkable
      decrease in blood flow in the LAD during rapid atrial pacing (130 bpm), and the
      preoperative reduction ratio was calculated as 24% compared with postoperatively.
      These findings suggest that coronary steal phenomenon was involved in myocardial
      ischemia in this patient.

PMID- 8523265
TI  - [Molecular pharmacological and toxicological studies of drug-metabolizing
      enzymes].
AB  - Studies on drug metabolism have opened new fields in the evaluation of drug
      efficacy and drug safety in experimental animals and humans, especially in the
      development of new drugs. The author described the history of discoveries of
      induction and inhibition of drug-metabolizing enzymes as a key point in the
      development of drug interaction studies. Studies on the sex-related differences
      in drug-metabolism have been important fields for understanding the sex-related
      toxicity and efficacy of drugs and their species differences under normal and
      pathological conditions. Rats are unique animals among experimental animals and
      humans. The activities of hepatic drug-metabolizing enzymes, especially
      cytochrome P450 and sulfotransferase, are regulated through the sex-related
      secretion pattern of growth hormone. The drug-metabolizing enzymes convert drugs
      into not only inactive metabolites, but produce toxic intermediates which cause
      mutagenesis, carcinogenesis and drug-caused allergic reactions. The author
      carried out extensive studies on the metabolic activation of mutagenic
      carcinogenic arylamines and demonstrated important roles of O-acetylation and O
      sulfation to cause DNA damages by N-hydroxyarylamines. Pharmacogenetic studies on
      hamster acetyltransferase were described to understand the individual differences
      in polymorphic acetylation of arylamines and N-hydroxyarylamines in relation to
      DNA damages. Finally, the author emphasizes important roles of drug metabolism
      studies for the development of new drugs by showing a prototype, which has
      multiple metabolic pathways by multiple enzymes and this shows reduced-extents of
      individual differences, for increasing efficacy and safety in a future clinical
      drug therapy.

PMID- 8523266
TI  - [Studies on structure of light degradation products of (-)-(S)-10-(1
      aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihyd ro-7H- pyrido[1,2,3
      de][1,4]benzoxazine-6-carboxylic acid (T-3761) in aqueous solution and solid
      state].
AB  - The structures of light degradation products of (-)-(S)-10-(1-aminocyclopropyl)-9
      fluoro-3-methyl-7-oxo-2,3-dih ydr o-7H- pyrido[1,2,3-de][1,4]benzoxazine-6
      carboxylic acid (T-3761) in aqueous solution and in the solid state were
      investigated. In aqueous solution, ten products were detected using HPLC and in
      the solid state, one main product was detected. All these light degradation
      products were isolated and their structures were elucidated. It was revealed that
      in almost all light degradation products only the 1-aminocyclopropyl side chain
      at the 10-position of T-3761 is changed to various structures by light oxidation.
      Surprisingly we found a unique light degradation product, in which carboxylic
      acid at the 6-position of T-3761 is changed to the hydroxy moiety.

PMID- 8523267
TI  - [Aerosolization of lactide/glycolide copolymer (PLGA) nanospheres for pulmonary
      delivery of peptide-drugs].
AB  - Lactide/glycolide copolymer (PLGA) nanospheres with nafarelin acetate (NA) used
      as a model peptide-drug have been developed by the emulsion-phase separation
      method in an oil phase as reported previously. In the present study, the
      aerosolization of nanospheres in dry and wet dispersion methods was investigated
      in vitro to evaluate their applications to pulmonary delivery of peptide-drug.
      The size distribution of aerosolized nanosphere dispersions and pulmonary
      deposition behaviors of inhaled particles were investigated using a lazer
      diffraction light-scattering particle sizer and an artificial model lung (Cascade
      Impactor: CI), respectively. It was found that the freeze-drying of nanospheres
      with a hydrophilic surface active agent effectively improved the inhalation
      behavior. Further, the mixing of nanospheres with lactose led to the reduction of
      their adhesion to an inhalation device (Spinhaler). It was supposed that the
      mists of nanosphere-suspension generated from a jet nebulizer might be inhaled
      into the lower bronchus and alveolus, because their respirable fraction (RF)
      value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a
      pulmonary inhalation index, reached a maximum of over 50%.

PMID- 8523268
TI  - [Examination of toxin production from environmental Bacillus cereus and Bacillus
      thuringiensis].
AB  - Emetic toxin- and entero toxin-producing activities were examined for 524 strains
      of Bacillus cereus and 90 strains of Bacillus thuringiensis to determine the
      distribution and contamination in natural environment, including foods,
      vegetable, soil and etc. Emetic toxin was assayed by the production of acid from
      HEp-2 cells induced by the culture supernatants of Bacillus, which was developed
      as an improved method for the detection of B. cereus heat-stable emetic-toxin by
      us. In the 524 strains of B. cereus tested, 11 out of 60 strains obtained from
      bean paste and 5 out of 20 strains obtained from peach produced emetic toxin
      which was detected by the HEp-2 cell method. All these emetic toxin-producing
      isolate strains were classified into H1 serotype. The 90 strains of B.
      thuringiensis did not produce emetic toxin, but the 47 strains produced entero
      toxin.

PMID- 8523269
TI  - [Screening of phagocyte activators in plants; enhancement of TNF production by
      flavonoids].
AB  - The tumor necrosis factor (TNF) was first discovered as a substance that induced
      necrosis of transplanted tumors. Recently, TNF has been recognized as an
      important and endogenous mediator in host defense mechanisms. To prove the fact
      that plant foods contain substances which activate the host defense mechanisms,
      we first examined if the administration of flavonoids could induce TNF production
      in mice. Some selected flavonoids such as naringin, apiin, poncirin and rutin
      were shown to amplify TNF release from murine macrophages in vivo in response to
      OK-432 as a second stimulus. However, their aglycone forms were not effective.
      The differences in the saccharide-chain of flavonoids induced the variety of TNF
      production.

PMID- 8523270
TI  - [Study on surfactin, a cyclic depsipeptide. I. Isolation and structure of eight
      surfuctin analogs produced by Bacillus natto KMD 2311].
AB  - Crude surfactin was simply prepared from the culture filtrate of Bacillus natto
      KMD 2311 twice by acidification of the filtrate and extraction of the precipitate
      with ethanol. Eight surfactin analogs were isolated from the crude surfactin by
      RP-HPLC and gel filtration. The structure of each analog was deduced by means of
      amino acid composition of the acid hydrolysate and FAB-MS measurement to be a
      cyclic depsipeptide containing a hydroxyfatty acid. The structure of the
      hydroxyfatty acid moieties was elucidated as n- or iso- or anteiso-3-hydroxyfatty
      acid composed of carbon number 13-16 by GC analysis and EI-MS after the
      methanolysis of the analogs. The amino acid sequence of the peptide portion was
      assigned as acyl-Glu-Leu-Leu-Val-Asp-Leu-Leu by EI-MS for eight analogs. The
      isolated four compounds were found to be identical with the known surfactin
      analogs, A1, B1, B2 and C1. Although surfactin A2 and C2 had not been isolated,
      their structures were deduced to be a surfactin analog. Surfactin A3 and D were
      novel analogs. The acyl groups of surfactin A2, A3, C2 and D were anteiso-3
      hydroxytridecanoic acid, n-3-hydroxytridecanoic acid, anteiso-3
      hydroxypentadecanoic acid and iso-3-hydroxyhexadecanoic acid, respectively.

PMID- 8523271
TI  - Clear lens extraction for anterior lenticonus.

PMID- 8523272
TI  - Phacoemulsification in a patient with torticollis.

PMID- 8523273
TI  - Phacoemulsification and silicone foldable intraocular lens implantation in a
      patient with chronic sarcoid uveitis.

PMID- 8523274
TI  - Consultation Section. How would you manage an eye that developed inflammatory
      response after uncomplicated phacoemulsification with intraocular lens
      implantation?

PMID- 8523275
TI  - Safe method for cleaning the posterior lens capsule.
AB  - Cleaning the posterior capsule is an important step in cataract microsurgery to
      prevent early postoperative visual impairment. A simple method for cleaning
      posterior lens capsule opacities during extracapsular cataract extraction is
      described. A straight 20-gauge cannula with a 0.3 mm anterior aspiration port,
      attached to a syringe with the piston removed, allows safe polishing in a deep
      anterior chamber. The described procedure has been safely performed in more than
      300 operations.

PMID- 8523276
TI  - Implantation of sutured posterior chamber intraocular lenses.
AB  - We describe a technique for implanting sutured posterior chamber intraocular
      lenses. Results of a small series using this technique in different clinical
      situations with at least 12 months follow-up are presented.

PMID- 8523277
TI  - Intracapsular posterior chamber intraocular lens insertion with posterior
      capsular tears or zonular instability.
AB  - A surgical technique is described for posterior chamber intraocular lens
      implantation within the capsular bag with a posterior capsular tear or weakened
      zonular support. Haptics are compressed before endocapsular insertion, minimizing
      capsular and zonular stress.

PMID- 8523278
TI  - Practice styles and preferences of ASCRS members--1994 survey.
AB  - A survey of the practice styles and preferences of the 1994 members of the
      American Society of Cataract and Refractive Surgery who had a U.S. ZIP code was
      performed in September 1994. Approximately 32% (1569) of the 4849 questionnaires
      mailed out were returned by the November cutoff date. Four main profile questions
      were used to cross-tabulate: age of the ophthalmologist, geographic location,
      volume of cataract surgery per month, and volume of refractive surgery per month.
      This report also compared the data with previously published surveys.

PMID- 8523279
TI  - Automated lamellar keratoplasty for the correction of hyperopia.
AB  - Hyperopic automated lamellar keratoplasty (H-ALK) is a refractive procedure that
      corrects low to moderate hyperopia of up to +5.00 diopters (D). In this
      retrospective series, we examined the efficacy, predictability, and safety of H
      ALK in 85 eyes in 49 patients. Follow-up was from 4 to 34 weeks (mean 18 weeks).
      Eyes were divided into three subsets: those in which we attempted an emmetropic
      result (n = 45), those in which we attempted to reduce, but not eliminate,
      hyperopia greater than 5.00 D (n = 23), and those in which we attempted a
      monovision result of -1.50 D (n = 17). In the eyes in which we attempted
      emmetropia, 76% achieved uncorrected visual acuity of 20/40 or better and 78.6%
      were within a range of -1.00 to +0.87 D. In those in which we attempted
      monovision, 47% achieved a spherical equivalent result between -2.50 and -1.00 D
      because of a tendency toward undercorrection. In those in which we attempted to
      reduce hyperopia, there was a mean correction of 4.33 D (standard deviation 1.36
      D), with a range of 2.12 to 6.75 D. The most significant complication was a
      reduction in best corrected visual acuity of one to three lines in 11 of 85 eyes;
      this was transient in six eyes. These preliminary results compare favorably with
      those of other procedures to correct hyperopia.

PMID- 8523280
TI  - Excimer laser photorefractive keratectomy for high myopia.
AB  - One hundred and thirty-three eyes of 103 patients had photorefractive keratectomy
      with a slit scan mode excimer laser for myopia ranging from -6.00 to -22.00
      diopters (D). The epithelium was removed with 20% ethanol, and the ablation was
      done with a tapered profile surrounding the optical zone. Patients were divided
      into two groups based on preoperative myopia: Group A, -6.00 D to -12.00 D (88
      eyes); Group B, -12.50 D to -22.00 D (45 eyes). In Group A, mean preoperative
      refraction was -9.59 +/- 1.79 D. Mean postoperative refraction was -0.29 +/- 1.47
      D at one month, -0.85 +/- 1.68 D at three months, -1.17 +/- 2.04 D at six months,
      and -0.56 +/- 0.74 D at one year. Anterior stromal haze was greatest at the end
      of the first month; it diminished thereafter. This haze did not reduce the best
      corrected visual acuity in any eye in Group A. Mean preoperative refraction in
      Group B was -14.69 +/- 5.27 D. Mean postoperative refraction was -1.34 +/- 2.02 D
      at one month, -0.76 +/- 2.08 D at three months, -3.88 +/- 2.32 D at six months,
      and -5.50 +/- 5.00 D at one year. Three eyes in Group B lost one or two lines of
      best corrected visual acuity as a result of severe stromal haze and epithelial
      scarring. Group A's results were similar to those obtained in eyes with low
      myopia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523281
TI  - High frequency ultrasound evaluation of radial keratotomy incisions.
AB  - Radial keratotomy is a surgical procedure to correct myopia that involves placing
      corneal incisions of precise partial thickness to induce flattening. It has
      yielded positive but sometimes unpredictable results. Many surgical variables
      influence the final result. Among them, incision depth is probably the most
      difficult to control and evaluate. In this study, we used very high frequency (50
      MHz) ultrasound (HFU) to image radial keratotomy incisions in post-radial
      keratotomy human corneas to obtain high definition images of the cornea. The
      images allowed us to measure the depth of incisions as a percentage of corneal
      thickness.

PMID- 8523282
TI  - Cyclotorsion in the seated and supine patient.
AB  - We used Maddox double-rod measurements to determine if positionally induced
      ocular cyclotorsion occurs when a patient moves from the seated to supine
      position. Maddox double-rod measurements were determined twice while patients (N
      = 30) viewed a fixation light at a distance of 7 feet in both the seated and
      supine positions. The difference between axis measurements made in seated and
      supine positions was not statistically significant. There was also no significant
      difference between the two measurements made in the seated and in the supine
      positions. These data show that the eyes do not undergo positionally induced
      ocular cyclotorsion when a patient moves from a seated to a supine position.

PMID- 8523283
TI  - Contour resolution of the EyeSys Corneal Analysis System.
AB  - We investigated the accuracy of a conventional videokeratography instrument
      (Corneal Analysis System, EyeSys Laboratories) to measure contour information
      using specialized software developed by the manufacturer. Seven calibrated
      spheres were measured and the results tabulated. A contour resolution for all
      spheres for all reflected rings was found to be +/- 0.0047 mm, representing a 95%
      confidence interval. This level of resolution is high enough to obtain clinical
      value from using the EyeSys instrument as a contour measuring device.

PMID- 8523284
TI  - Comparison of three keratometry instruments.
AB  - We compared the reliability of measurements of three keratometers and keratometry
      readings from a corneal topography system to determine if they were as accurate
      as the "gold standard" Javal-Schiotz keratometer. Same-day measurement of the
      steepest and flattest powers of the central 3 mm of the corneas of 200 eyes (100
      patients) revealed no statistically significant difference in reliability between
      the newer keratometers and the Javal-Schiotz. In addition, the newer machines are
      more convenient and efficient in some clinical settings.

PMID- 8523285
TI  - Comparative study of three semiautomated specular microscopes.
AB  - We compared two clinical video-assisted specular microscopes (Zeiss, noncontact,
      and the wide-field Keeler Konan sp 3300, contact) with an autofocus microscope
      (Konan noncon Robo-ca sp 8000, noncontact) with built-in analyzing software by
      studying the morphometry of the central corneal endothelium of 12 eyes in 12
      patients. The mean coefficients of variation of the cell size analysis of three
      successive images per cornea for the three methods were 3.9%, 4.0%, and 2.2%,
      respectively. One-way analysis of variance showed a significant difference in the
      mean cell area measured with the three methods; there was no significant
      difference in the results of hexagonality (pleomorphism) and coefficient of
      variation (polymegathism). Although each microscope showed a high
      reproducibility, we do not recommend using the three interchangeably. The Konan
      noncon Robo-ca sp 8000 specular microscope provides a rapid morphometric
      endothelial analysis. The Keeler Konan sp 3300 is better for more detailed
      studies and photography of the corneal endothelium.

PMID- 8523286
TI  - Comparison of the induced astigmatism after temporal clear corneal tunnel
      incisions of different sizes.
AB  - A prospective, randomized study compared the surgically induced astigmatism after
      3.5 mm, 4.0 mm, and 5.0 mm temporal corneal tunnel incisions over six months. We
      studied 60 eyes of 60 patients who had phacoemulsification through a two-step
      clear corneal tunnel incision and implantation of one of three posterior chamber
      intraocular lenses (IOLs). Patients were divided into three groups of 20 each:
      Group A, cartridge injection of a foldable plate-haptic silicone IOL through a
      3.5 mm self-sealing incision; Group B, cartridge injection of a disc silicone IOL
      through a 4.0 mm self-sealing incision; Group C, 5.0 mm optic poly(methyl
      methacrylate) IOL through a 5.0 mm incision with one radial suture. Corneal
      topography data were obtained using a computerized videokeratographic analysis
      system preoperatively and one week and six months postoperatively. Vector
      analysis was performed to calculate the surgically induced astigmatism. After the
      first postoperative week, mean induced astigmatism was 0.63 diopters (D) (+/-
      0.41) in Group A, 0.64 D (+/- 0.35) in Group B, and 0.91 D (+/- 0.77) in Group C.
      After six months, it was 0.37 D (+/- 0.14) in Group A, 0.56 D (+/- 0.34) in Group
      B, and 0.70 D (+/- 0.50) in Group C. Surgically induced astigmatism was
      significantly lower in Group A than in Group B (P < .05) and Group C (P < .005)
      after six months. Vector analysis demonstrated that temporal corneal tunnel
      incisions induced clinically minimal astigmatism over six months postoperatively
      depending on incision size.

PMID- 8523287
TI  - Corneal sensation after small incision, sutureless, one-handed
      phacoemulsification.
AB  - Corneal sensitivity was measured in 60 eyes preoperatively and at one day, one
      week, and one month after small incision, sutureless, one-handed
      phacoemulsification performed by the same surgeon using the same technique.
      Corneal sensation remained normal at the center and the 3, 6, and 9 o'clock
      positions. Decreased corneal sensation was found over the width of the scleral
      tunnel incision at the limbus, extending in a wedge-shaped sector not
      encompassing the central cornea.

PMID- 8523288
TI  - Long-term astigmatic changes after phacoemulsification with single-stitch,
      horizontal suture closure.
AB  - We analyzed postoperative corneal astigmatism in 32 eyes followed for three years
      after small incision phacoemulsification with a 4 mm scleral tunnel incision and
      a single-stitch, horizontal suture technique. Sutures were left intact
      postoperatively. Mean surgically induced cylinder was 0.63 diopters (D) at one
      day postoperatively, -0.01 D at one year, and -0.07 D at three years. A
      significant number of eyes showed an initial shift toward with-the-rule
      astigmatism. At one year, the axis had nearly returned to preoperative
      orientation without further against-the-rule shift after three years. An
      uncorrected visual acuity of 20/40 or better was found in 43.8% of the patients
      at one week postoperatively and in 62.5% at one and three years. Best corrected
      visual acuity of 20/40 or better was found in 62.5%, 90.6%, and 93.7%,
      respectively.

PMID- 8523289
TI  - Astigmatic decay following small incision, self-sealing cataract surgery: one
      year follow-up.
AB  - Twenty patients who had phacoemulsification using a small, self-sealing incision
      were evaluated one year after surgery for astigmatic changes. Keratometric
      analysis was performed using the EyeSys photokeratoscope, and data for the 3 mm
      corneal zone for each patient were recorded. Results were compared with those
      reported for the one-week and one-month postoperative periods. From one month to
      one year, a minimal amount of additional against-the-rule change in cylinder
      occurred. Because the range of changes was broad, it was difficult to predict the
      direction of astigmatic change (i.e., against the rule versus with the rule) that
      would occur over time for a given patient.

PMID- 8523290
TI  - Comparison of the Storz bifocal zonal and the 3M diffractive multifocal
      intraocular lenses.
AB  - Visual acuity and contrast sensitivity after cataract surgery were evaluated in
      best-case eyes that received a Storz bifocal zonal intraocular lens (IOL) or a 3M
      diffractive multifocal IOL. A group of eyes with a monofocal IOL was used as a
      control. Postoperatively, all eyes had a best corrected visual acuity of 20/40 or
      better. At near, wearing the best distance correction, 86.0% of the Storz group
      and 94.5% of the 3M group had a visual acuity of 20/40 or better. Both the Storz
      and 3M groups had a significantly greater loss in visual acuity in dim light at
      the lowest contrast levels than the monofocal group. Under bright light, the
      Storz group's contrast sensitivity was not significantly different from that of
      the monofocal groups; however, the 3M group's contrast sensitivity decreased at
      all levels of contrast. The Storz lens performed slightly but significantly
      better than the 3M lens in bright light (96% and 25% Regan levels), perhaps
      because of the difference in IOL optics or small differences in the incidence of
      posterior capsule opacification, for which this study was not controlled. In the
      Storz and 3M groups, distance visual acuity was better than distance visual
      acuity using a minus addition, which makes the patient use the near portion of
      the optic.

PMID- 8523291
TI  - Effect of silicone sound speed and intraocular lens thickness on pseudophakic
      axial length corrections.
AB  - We compared the sound speeds of SLM-1/UV (990 M/sec at 35 degrees Celsius
      [degrees C]), SLM-2/UV (1090 M/sec at 35 degrees C), and Perspex CQ poly(methyl
      methacrylate)(2658 M/sec at 35 degrees C). Methods are presented to determine the
      correction of axial length (CAL) factors for axial length measurements made on
      pseudophakes with AMO PhacoFlex Si-18, Si-26 (SLM-1/UV), and AMO PhacoFlex II SI
      20 or SI-30 (SLM-2/UV) silicone intraocular lenses (IOLs). A CAL is required to
      avoid potential errors with secondary IOL power predictions; CALs, which are
      strongly dependent on the material sound speed and less so on lens thickness,
      ranged from -0.65 mm to -1.20 mm for SLM-1/UV silicone IOLs and from -0.35 mm to 
      0.55 mm for SLM-2/UV silicone IOLs. The sound speeds of IOL materials varied
      insignificantly between ambient room temperature (23 degrees C) and intraocular
      temperature (35 degrees C).

PMID- 8523292
TI  - Pathology of silicone intraocular lenses in human eyes obtained postmortem.
AB  - The increased use of phacoemulsification and small incision surgery has led to
      interest in a soft intraocular lens (IOL) for implantation after cataract
      extraction. We present the pathologic findings of seven eyes obtained postmortem
      from five patients with silicone IOLs. Length of implantation ranged from 6 weeks
      to 13 months. There was symmetric bag-bag fixation in all cases. Two IOLs had
      distorted and compressed polypropylene loops, resulting in decentration. The
      silicone IOL appeared to be well tolerated in all cases.

PMID- 8523293
TI  - One-year results of the intrascleral glaucoma implant.
AB  - This is an initial report from a study to determine the safety and efficacy of an
      implant placed within the sclera to relieve elevated intraocular pressure (IOP).
      It describes the first eight patients to receive the implant. Intraocular
      pressure and pneumotonometry were evaluated preoperatively and postoperatively
      for one year. In five patients, IOP decreased. Three patients in which the
      implant was considered a failure because of wound leaks had patch grafts, removal
      of the implant, or both. The five successful cases have continued to show reduced
      IOP.

PMID- 8523294
TI  - Refraction and anterior chamber depth before and after neodymium: YAG laser
      treatment for posterior capsule opacification in pseudophakic eyes: a prospective
      study.
AB  - Anterior chamber depth and refraction were evaluated in 52 pseudophakic eyes
      before and about one month after neodymium: YAG laser capsulotomy for posterior
      capsule opacification. External anterior chamber depth averaged 4.06 mm before
      and 4.07 mm after laser treatment, a statistically insignificant change. Mean
      spherical equivalent refraction before laser treatment, estimated from the
      prescription of spectacles, was 0.30 diopters (D). Mean subjective refraction
      after laser treatment was 0.24 D. The difference was not significant. Mean
      capsulotomy opening diameter increased from 3.44 mm +/- 0.61 mm (+/- SD)
      immediately after the laser treatment to 3.67 mm +/- 0.61 mm one month later. The
      increase was statistically significant. Intraocular lens position and spherical
      equivalent refraction did not change after the YAG laser capsulotomy, despite a
      significant increase in area of the capsulotomy opening.

PMID- 8523295
TI  - Effects of diclofenac sodium and indomethacin on proliferation and collagen
      synthesis of lens epithelial cells in vitro.
AB  - We investigated the effects of diclofenac sodium and indomethacin on the
      proliferation of and collagen synthesis by lens epithelial cells (LECs) of human
      cataracts in culture. The anterior capsule with attached LECs, obtained by
      anterior capsulotomy during cataract surgery, was cultured directly without cell
      dispersion. When the culture became almost confluent, diclofenac sodium or
      indomethacin at various concentrations was added to the incubation medium. The
      incorporation of 3H-thymidine and 3H-proline into the LECs was measured after the
      cells were labeled with these radioactive materials. Both drugs greatly
      suppressed the incorporation of 3H-thymidine and of 3H-proline, indicating that
      they inhibit cell division and collagen synthesis by LECs. Both drugs may help
      prevent posterior capsule opacification.

PMID- 8523296
TI  - Natural history of cellular deposits on the anterior intraocular lens surface.
AB  - Previous cytopathological studies have demonstrated the presence of cellular
      deposits on the poly(methyl methacrylate) (PMMA) intraocular lens (IOL) surface.
      In this prospective study, IOL surface specular microscopy was used to document
      the natural history of these deposits in the first year following PMMA IOL
      implantation. Intraocular lens surface specular microscopy was performed 1, 3, 6,
      and 12 months after endocapsular cataract surgery in 27 otherwise normal eyes.
      Postoperatively, IOLs were assessed for the presence of inflammatory cells, with
      the number of cells graded from 0 (none) to 4 (many). Two inflammatory cell types
      were visualized: small and giant cells. Small cells were found on 81.5% of IOLs
      at 1 month, 73.1% at 3 months, and 30.4% at 12 months. Small cells were found in
      only small numbers (peak mean cell score of 1.26 +/- 0.94 at 1 month). Giant
      cells were found on 59.3% of lenses at 1 month, 73.1% at 3 months, and 39.1% at
      12 months. The number of giant cells on each lens peaked at 3 months (mean cell
      score 2.0 +/- 1.55), when 50% of lenses achieved a giant cell score of 3 or 4.
      Inflammatory cell deposits are, therefore, a normal occurrence on the PMMA IOL
      surface for up to 1 year after surgery. This cellular response consists of two
      distinct processes: a small cell response, which peaks by 1 month, and a later
      giant cell response, which peaks at 3 months.

PMID- 8523297
TI  - Is the sutureless cataract incision a valve for bacterial inoculation?
AB  - Many cataract surgeons perform sutureless surgery to decrease operating time,
      postoperative astigmatism, and healing time. Anecdotal case reports of
      postoperative endophthalmitis after sutureless surgery prompted our investigation
      of this type of wound closure and its possible relationship to an increased
      incidence of infection. This in vitro study addressed the question: Is sutureless
      more likely than sutured cataract surgery to provide a route for inoculation of
      microbial organisms into the eye? Twenty-eight human eyes obtained postmortem
      were randomly divided into 14 pairs and successively incubated for 90, 150, 210,
      and 270 minutes each in a suspension of Staphylococcus epidermidis in physiologic
      media. Cultured aqueous aspirates yielded no significant differences between
      sutured and unsutured eyes in colony counts at any time interval. This suggests
      that both sutured and unsutured wounds resist bacterial ingrowth equally and that
      a properly constructed unsutured wound is not a significant valve for bacterial
      inoculation in an eye pressurized to physiological conditions.

PMID- 8523298
TI  - Subconjunctival hyaluronidase injection producing temporary myopia.
AB  - A subconjunctival hyaluronidase injection, given to resolve hemorrhaging after a
      bout of severe coughing, produced myopia in a 30-year-old female. The myopia
      resolved after 45 days of no treatment other than repeated examinations.

PMID- 8523299
TI  - The changing scene in breast surgery in a plastic surgery unit (1966-94).
AB  - A review of the increasing numbers and problems concerning breast surgery over
      almost 30 years is related. The current controversies and changing techniques are
      discussed. Breast reduction is confirmed to be a very useful operation, being a
      cosmetic as well as symptomatically beneficial procedure. It is seen to be a
      cause of a major increase in the unit's workload as its popularity increases.
      Various options for breast reconstruction after excisional surgery are discussed.

PMID- 8523300
TI  - Management of retained Foley catheters.
AB  - Failure to deflate Foley catheters is a rare problem in clinical practice. There
      are various methods to overcome this problem. This is an experimental study of
      the commonly used methods. The balloons should never be inflated until rupture to
      prevent leaving loose fragments. A ureteric catheter or its stylet can be used to
      deflate the balloon. The balloon can be ruptured with fine needle under
      ultrasound guidance but it should not have been inflated to more than 50% of its
      volume to prevent leaving loose fragments in the bladder.

PMID- 8523301
TI  - Post-mastectomy seroma: a new look into the aetiology of an old problem.
AB  - Postmastectomy seroma (PMS) remains an unresolved quandary as the risk factors
      for its formation have still not been identified. Sixty-four consecutive female
      patients undergoing Halsted mastectomy were prospectively studied for this
      purpose. The risk factors that were studied included age and weight, diabetes,
      hypertension, tumour (size and location) and nodal (positive or negative) status
      and the use of perioperative blood transfusion. Additionally, the effect of PMS
      on total hospital drainage (THD), post-operative hospital stay and other wound
      related complications were assessed. The incidence of PMS in this study was 28%,
      and those patients with PMS were designated as group A while the remaining
      patients were designated as group B. Group A patients were significantly older (P
      < 0.02) and heavier (P < 0.05) than group B patients; also, there were
      significantly (P < 0.0001) greater number of hypertensive patients in group A
      than in group B. In terms of other risk factors the two groups were statistically
      similar. Group A patients had significantly greater (P < 0.01) amount of THD than
      group B patients. Although no septic complications were observed as a result of
      seroma, its presence significantly (P < 0.0001) lengthened the post-operative
      hospital stay in group A patients. It is concluded that (1) PMS is a common
      problem, (2) its occurrence significantly increases the post-operative hospital
      stay, and (3) hypertension is perhaps the most important risk factor for its
      causation. Hypertension contributes to seroma formation, probably by way of
      prolonged oozing from the large mastectomy wound.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523302
TI  - A prospective randomized study of self-dilatation in the management of urethral
      strictures.
AB  - Over a 3-year period 51 patients with urethral strictures were treated by
      internal urethrotomy and then either randomly allocated to a course of post
      operative dilatation or no dilatation. The patients in the self-intermittent
      dilatation (SID) group were shown how to pass a 16-F catheter through the
      stricture but not into the bladder. Complete follow-up was available in 44
      patients, 32 of whom had new strictures while 12 had recurrent strictures. Of the
      patients with new strictures 13 (76%) in the SID group and 12 (80%) in the non
      SID group achieved a satisfactory result (a flow rate > 12 ml per second) at one
      year (chi 2 = 0.18, P = 0.67). In the 12 patients with recurrent strictures 4
      (66%) patients in the SID group and 1 (17%) patient in the non-SID group achieved
      a satisfactory result (chi 2 = 3.09, P = 0.079). In both groups results were not
      statistically significant. The technique of short-term postoperative self
      dilatation does not seem to prevent recurrent strictures in patients treated with
      internal urethrotomy.

PMID- 8523303
TI  - Varicose vein surgery: patient satisfaction.
AB  - Surgery for varicose veins is a common surgical procedure performed for various
      indications including cosmesis. Patient satisfaction with the eventual outcome is
      therefore important. A total of 311 patients (68%), who underwent varicose vein
      surgery during a 10-year period, replied to a postal survey of 456 patients
      [National Health Service (NHS) 327: private patients (PP) 129]. Of those 311, 19%
      of the NHS patients compared with 34% of the PP were completely satisfied with
      the surgery, the communication and had had no post-operative complications (P <
      0.01). Twenty-six per cent of the NHS patients were very dissatisfied with their
      treatment compared with 13% of the PP (P < 0.025). The majority of dissatisfied
      patients were female (P < 0.005). These results suggest that while varicose vein
      surgery is regarded as a safe and often minor procedure, it is associated with a
      significant surgical morbidity and patient dissatisfaction. Patients should be
      made aware of the potential outcome prior to surgery.

PMID- 8523304
TI  - Early patient discharge following appendicectomy: safety and feasibility.
AB  - One hundred and twenty patients with non-perforated acute appendicitis were
      discharged within 72 h of operation; 50 left hospital within 48 h of surgery.
      Criteria adopted for early discharge were: stable vital signs, active bowel
      sounds, ambulation and ability to tolerate fluid and food without discomfort. The
      patient's contact address was taken and every patient was requested to report to
      the out-patient department on the 7th post-operative day to remove stitches and
      assess the wound. There were three re-admissions. Five patients, however
      developed wound problems, three had wound infections, one had an indurated
      painful wound and the last developed erythema; the latter two patients were
      treated on an out-patient basis. Twenty patients were not happy about early
      discharge. Early discharge following appendicectomy is safe and can be practiced
      in uncomplicated cases of acute appendicitis.

PMID- 8523305
TI  - Thoracoscopic management of thoracic duct injury.
AB  - Thoracotomy has long been the conventional surgical approach in dealing with
      chylothorax due to thoracic duct injury which has been refractory to conservative
      treatment. The development of thoracoscopic access provides an alternative means
      of dealing with thoracic duct injuries thereby reducing the morbidity from
      thoracotomy and prolonged chylous leak. It will encourage earlier intervention in
      thoracic duct injury.

PMID- 8523306
TI  - Management of benign oesophageal stricture by total fundoplication gastroplasty.
AB  - In the Department of Thoracic Surgery, City Hospital, Nottingham, we use total
      fundoplication gastroplasty routinely in the management of patients with benign
      peptic strictures who are unresponsive to medical treatment. This is an analysis
      of our results between 1983 and 1987. Fifty-six patients are included. There was
      no operative mortality. An overall good result was achieved in 83.9% of the
      patients. The results were better earlier in the disease (86.7% in grade II and
      90.3% in grade I) than later (60% in grade III). We believe that conservative
      surgery should not be unduly delayed once medical management has failed. We now
      reserve resection for patients with fibrotic undilatable strictures and failures
      of conservative surgery.

PMID- 8523307
TI  - Dilatation of the left colon with a Foley catheter: an aid to staple anastomosis.
AB  - Balloon dilatation of the left colon using a Foley catheter was performed in 26
      patients prior to staple anastomosis. A 28-mm stapler was then used in six (23%)
      patients, a 29-mm in seven (27%), a 31-mm in eleven (42%) and a 33-mm in two
      (8%). Two anastomoses failed (7.9%) and one patient developed local recurrence.
      None of the remainder developed a symptomatic stricture. Flexible sigmoidoscopy
      was performed on 18 patients at least 3 months after surgery, revealing that one
      (5.5%) had developed an asymptomatic stricture. A 28-mm stapler had been used in
      this case. This technique of dilating the left colon with a Foley catheter is a
      useful aid to staple anastomosis in large bowel surgery.

PMID- 8523308
TI  - Thyroid malignancy in multinodular goitre and solitary nodule.
AB  - This is a retrospective study of 361 thyroid specimens during a 6 1/2-year period
      with the objective of investigating the prevalence and pattern of thyroid
      malignancy associated with multinodular goitre (MNG) and solitary nodule (SN).
      Fourteen of 172 MNG (8%) and 16 of 105 SN (15.2%) were associated with
      malignancy, a statistically insignificant difference (P = 0.06). Unlike in males,
      malignancy was significantly commoner in females with SN than those with MNG (P =
      0.03) and generally occurred at a significantly older age (P < 0.05). On
      analysing thyroid carcinoma and lymphoma separately, patients with SN had a
      higher incidence of carcinoma compared with those with MNG (P = 0.01). It is
      concluded that surgical intervention may be the appropriate method of treating
      male patients presenting with MNG. However, in females, conservative management
      of MNG should be adopted unless surgery is indicated depending on clinical
      judgement and, if feasible, the result of fine needle aspiration biopsy.

PMID- 8523309
TI  - An audit of mortality in patients with pressure sores admitted to a regional
      plastic surgery unit over a 20-year period (1972-92).
AB  - A retrospective review of the annual mortality records over the last 20 years of
      Bangour General Hospital Plastic Surgery Unit gave a total of 212 deaths, 10 of
      which occurred in patients admitted with pressure sores. The significance of this
      is discussed, particularly related to the changing situation in the organization
      of the National Health Service. The mortality rate for patients with pressure
      sores was 3%.

PMID- 8523310
TI  - Surgery for pharyngeal pouch: audit of management with short- and long-term
      follow-up.
AB  - A review was undertaken of 103 patients with pharyngeal pouch presenting over a
      10-year period. Management was conservative in 35 patients and 68 patients were
      treated using external diverticulectomy and cricopharyngeus myotomy. The fistula
      rate was 8.9% and median hospital stay was 7 days. The results of this large
      series are compared to other reported series, and a long-term follow-up showing
      clinical outcome is reported.

PMID- 8523311
TI  - Rapid-fractionation pre-operative chemoradiation for malignant periampullary
      neoplasms.
AB  - The multimodality treatment of adenocarcinoma of the pancreatic head has been
      shown to improve survival compared with surgery alone. The delivery of
      chemotherapy and radiation therapy (chemoradiation) before rather than after
      pancreaticoduodenectomy ensures that all patients who undergo surgery receive the
      other components of multimodality therapy. In an effort to reduce overall
      treatment time and cost, the use of rapid-fractionation preoperative
      chemoradiation was explored. Radiation therapy was delivered with 18-MeV photons
      to a total dose of 30 Gy given in 10 fractions over 2 weeks. 5-Fluorouracil was
      given concurrently by continuous infusion at a dose of 300 mg m-2 day-1. Four
      weeks after the completion of chemoradiation, patients underwent
      pancreaticoduodenectomy and electron-beam intraoperative radiation therapy (10
      Gy). All patients completed the treatment programme without delay. The rapid
      fractionation programme was delivered at nearly half the cost of standard
      chemoradiation and histologic evidence of tumour cell injury was present in all
      resected specimens. There were no perioperative anastomotic complications, and
      median hospital stay was 20 days. Rapid-fractionation chemoradiation warrants
      further study in the neoadjuvant setting.

PMID- 8523312
TI  - Aneurysms of the infrapopliteal arteries.
AB  - Atherosclerotic aneurysms involving only infrapopliteal arteries are extremely
      rare. The present report describes a patient with two completely separate
      aneurysmal dilatations involving the tibioperoneal trunk and the anterior tibial
      artery. To our knowledge, this condition has not been previously described. An
      international bibliographic review was also made, collecting four patients
      affected by atherosclerotic infrapopliteal aneurysms. Clinical presentation,
      radiographic findings, and surgical management are discussed.

PMID- 8523313
TI  - A crowded ureter.

PMID- 8523314
TI  - Streptococcal myositis and the acute abdomen: a case report.
AB  - Spontaneous streptococcal myositis, previously rare, is now reported more
      frequently. The condition is caused by overwhelming group A beta-haemolytic
      streptococcal infection and is not necessarily fatal.

PMID- 8523315
TI  - Critical appraisal and current position of laparoscopic hernia repair.
AB  - Laparoscopic hernia repair is still undergoing development and appraisal. This
      review briefly outlines the history of hernia repair. The six techniques of
      laparoscopic repair are described and published experience for each of these is
      discussed. The techniques, which involve simple closure of the neck of the
      hernial sac with or without closure of the internal ring, appear to have little
      or no place in adult practice. The plug technique and plug and patch technique
      represented a transient phase of development and have now been abandoned. Suture
      techniques have not been widely practised, making current appraisal difficult. Of
      the mesh techniques the intraperitoneal onlay mesh technique is not recommended.
      The place of the transabdominal preperitoneal technique and the extraperitoneal
      technique need to be determined by prospective randomized clinical trials.

PMID- 8523316
TI  - Cervical spine fractures.
AB  - A classification of cervical spine injuries based upon Dunn's concept of stable
      and unstable fractures is presented. The role of conservative treatment using
      Halo-body fixation is outlined along with the various approaches to the cervical
      spine and their method of ensuring stability.

PMID- 8523317
TI  - Skin closure using nylon and polydioxanone: a comparison of results.
AB  - Nylon vertical mattress sutures and interrupted subcuticular polydioxanone (PDS)
      sutures have been used for skin closure. The complications and cosmetic results
      of each have been noted in a prospective trial of 93 hip wounds. When nylon
      sutures are used there is an increased incidence of erythema and the final scar
      is less cosmetically attractive. Interrupted PDS sutures take longer to insert
      but have few complications and are recommended in both the young and elderly
      patients.

PMID- 8523318
TI  - External fixation for tibial fractures: clinical results and cost effectiveness.
AB  - We report our experience with the Orthofix external fixator in the management of
      closed and Gustilo grades 1 and 2 compound unstable tibial shaft fractures. Forty
      four fractures were treated between January 1988 and December 1989. All the
      fractures united. Median time in hospital was 13 days. Median time to union was
      21 weeks for closed and 22 weeks for compound fractures. A method of estimating
      the overall cost per patient is described. Using this method we compared the cost
      of using the Orthofix with that of intramedullary nailing and plating according
      to AO principles. The Orthofix fixator was cheaper than alternative methods in
      particular because no readmissions were required for implant removal.

PMID- 8523319
TI  - Hypophosphatemia associated with enteral alimentation in cats.
AB  - Hypophosphatemia is uncommon in cats, but it has been reported in association
      with diabetes mellitus and hepatic lipidosis, where it can cause hemolysis,
      rhabdomyopathy, depression, seizures, and coma. The purpose of this article is to
      describe 9 cats that developed low serum phosphorus concentrations (< 2.5 mg/dL)
      subsequent to enteral alimentation. Serum biochemical analyses from more than
      6,000 cats were reviewed. The medical records of all cats with hypophosphatemia
      were examined for history of enteral alimentation; diabetic cats were excluded
      from the study. Nine cats, ranging in age from 3 to 17 years, were identified.
      All cats had normal serum phosphorus concentrations before tube feeding began.
      Onset of hypophosphatemia occurred 12 to 72 hours after initiation of enteral
      alimentation, and the nadir for phosphorus concentrations ranged from 0.4 to 2.4
      mg/dL. Hemolysis occurred in 6 of the 9 cats. Hypophosphatemia secondary to
      enteral alimentation is an uncommon clinical finding in cats. Cats with high
      alanine aminotransferase activity, hyperbilirubinemia, and weight loss should be
      closely monitored for hypophosphatemia during the first 72 hours of enteral
      alimentation.

PMID- 8523320
TI  - Acute and short-term hemodynamic, echocardiographic, and clinical effects of
      enalapril maleate in dogs with naturally acquired heart failure: results of the
      Invasive Multicenter PROspective Veterinary Evaluation of Enalapril study. The
      IMPROVE Study Group.
AB  - The efficacy of enalapril maleate in dogs with naturally acquired class III or
      class IV heart failure was evaluated in a multicenter study. Fifty-eight dogs
      with dilated cardiomyopathy (35 dogs), mitral regurgitation (22 dogs), or aortic
      regurgitation (1 dog) receiving conventional therapy for heart failure
      (furosemide with or without digoxin) were included in a randomized double-blind
      study. Thirty-one dogs received enalapril tablets PO at approximately 0.5 mg/kg
      body weight bid, and 27 dogs received placebo tablets PO bid. Physical,
      electrocardiographic, hemodynamic, echocardiographic, radiographic, and clinical
      examinations were performed on each dog before treatment and at the end of the
      approximately 21-day study. After treatment on day 0, the enalapril-treated dogs
      had significantly (P < .05) lower heart rate, mean systemic arterial blood
      pressure, and mean pulmonary arterial blood pressure than the placebo-treated
      dogs. Pulmonary capillary wedge pressure was marginally decreased (P = .0567) in
      the enalapril-treated dogs. When compared with those in the placebo-treated dogs,
      scores for pulmonary edema were significantly (P < .05) decreased on day 2 in the
      enalapril-treated dogs. At the end of the study, enalapril-treated dogs had
      significantly (P < .05) greater decreases in class of heart failure, pulmonary
      edema score, and mobility score relative to baseline, and had significantly (P <
      .05) better overall evaluation scores when compared with the placebo-treated
      dogs. This study shows the beneficial hemodynamic and clinical effects of adding
      enalapril to conventional therapy for dogs with heart failure.

PMID- 8523321
TI  - Controlled clinical evaluation of enalapril in dogs with heart failure: results
      of the Cooperative Veterinary Enalapril Study Group. The COVE Study Group.
AB  - The clinical efficacy and safety of enalapril were evaluated in dogs with
      moderate or severe heart failure. This study was conducted at 19 centers and
      included 211 client-owned dogs with heart failure caused by mitral regurgitation
      (MR) due to acquired valvular disease or dilated cardiomyopathy (DCM). Dogs of
      various breeds, ages, and weights were included in the study. Replicates of 2
      dogs each were formed, using separate allocation schedules for dogs with MR or
      DCM. One dog within each replicate received placebo tablets (vehicle tablets
      without enalapril) PO sid or bid, and the other dog received enalapril tablets at
      approximately 0.5 mg/kg sid or bid, based on individual need. In addition to the
      experimental drug, all dogs, except 1 in the placebo group, received furosemide;
      73.3% of the dogs in the placebo group and 78.3% of those in the enalapril group
      received digoxin. Doses of enalapril or placebo were administered for
      approximately 28 days. In the placebo group, 68.6% of the dogs completed the
      study compared with 84.9% in the enalapril group; the difference between groups
      was significant (P < .01). Significantly (P < .01) more dogs in the placebo group
      compared with the enalapril group died or were removed from the study because of
      progression of heart failure. On day 28, all 14 clinical variables measured
      improved significantly (P < .01) in the enalapril group compared with the placebo
      group. Five dogs (3 from the placebo group and 2 from the enalapril group) had to
      be removed from the study as a result of azotemia.

PMID- 8523322
TI  - Plasma taurine concentrations in normal dogs and in dogs with heart disease.
AB  - Plasma taurine concentrations were determined in 76 dogs with dilated
      cardiomyopathy (DCM), 28 dogs with acquired valvular disease (AVD), and 47 normal
      (control) dogs. The data were collected at 2 referral centers, The Animal Medical
      Center, New York, NY (AMC), and the University of California, Davis (UCD), and
      the studies were conducted independently. Different anticoagulants (sodium
      citrate at AMC and lithium heparin at UCD) were used to collect the plasma
      samples. Paired analysis of samples showed a significant difference in plasma
      taurine concentrations, depending on the anticoagulant used. Consequently,
      results from each clinic were analyzed separately. Plasma taurine concentrations
      were significantly higher in dogs with AVD (median, 133 nmol/mL; range, 25 to 229
      nmol/mL) than in control dogs (median, 63 nmol/mL; range 44 to 224 nmol/mL) and
      dogs with DCM (median, 72 nmol/mL; range, 1 to 247 nmol/mL) at AMC (P < .001).
      The number of dogs with AVD at UCD was too small to draw meaningful conclusions.
      At UCD, the median plasma taurine concentration was 98 nmol/mL (range, 28-169
      nmol/mL) in dogs with AVD, 75 nmol/mL (range, 0.1-184 nmol/mL) in dogs with DCM,
      and 88 nmol/mL (range 52-180 nmol/mL) in control dogs. There were no significant
      differences in plasma taurine concentrations between dogs with DCM and the
      control dogs at either hospital. Congestive heart failure and administration of
      cardiac medication had no significant effect on plasma taurine concentrations.
      Plasma taurine concentration was low (< 25 nmol/mL) in 17% (13/76) of the dogs
      with DCM. Seven of the 13 dogs with low plasma taurine concentrations were Cocker
      Spaniels or Golden Retrievers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523323
TI  - The effects of cyclosporine versus standard care in dogs with naturally occurring
      glomerulonephritis.
AB  - Glomerulonephritis (GN) is a leading cause of chronic renal failure in dogs.
      However, little is known about the efficacy of available treatment options for GN
      in this species. The purpose of this study was to determine the effects of
      cyclosporine (Cy) administration on the outcome of naturally occurring GN in
      dogs. Thirteen dogs from 4 institutions were included in the study. Randomization
      of dogs into placebo-versus Cy-treated groups was stratified according to initial
      morphological diagnosis and contributing institution. Seven and 6 dogs were
      assigned to be given placebo or Cy, respectively. The initial Cy dose of 10 mg/kg
      every 24 hours was adjusted to maintain 24-hour trough, whole blood Cy
      concentrations between 250 and 400 ng/mL. There were no statistically significant
      differences between placebo- and Cy-treated groups with respect to serum total
      protein, albumin, urea nitrogen and creatinine, and plasma protein
      concentrations; platelet count; urine protein-creatinine ratio; endogenous
      creatinine clearance; 24-hour urine protein concentrations; or 24-hour urine
      protein-endogenous creatinine clearance ratio. However, PCV was significantly
      lower in the Cy-treated group. Decreased appetite, diarrhea, vomiting, weight
      loss, involuntary shaking, and thrombocytopenia were noted in both treatment
      groups; however, clinical signs in Cy-treated dogs subjectively were more severe.
      One Cy-treated dog developed gingival hyperplasia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523324
TI  - Anti-liver membrane protein antibodies in dogs with chronic hepatitis.
AB  - Serum from 21 dogs with chronic hepatitis was evaluated for anti-liver membrane
      protein (anti-LMP) antibodies by an enzyme-linked immunosorbent assay. Ten of the
      21 dogs had anti-LMP antibody concentrations greater than 2 SD above the mean
      value for the 10 healthy control dogs; titers ranged from 1:40 to greater than
      1:1,600. Anti-LMP-positive dogs were not restricted by breed, had higher alanine
      amino transferase activity and total bilirubin concentration, and more severe
      liver lesions when compared with anti-LMP-negative dogs. This study provided
      evidence of humoral autoantibodies in dogs with chronic hepatitis, but it did not
      determine if the autoantibodies were primary or secondary.

PMID- 8523325
TI  - Medical management of right dorsal colitis in 5 horses: a retrospective study
      (1987-1993).
AB  - Right dorsal colitis in horses has been associated with administration of
      phenylbutazone. Although reports of right dorsal colitis in this species have
      described surgical treatment associated with a poor prognosis, we have had
      success treating this condition medically. This report describes 5 horses with
      right dorsal colitis confirmed during celiotomy that were initially managed
      medically. All horses had a history of intermittent abdominal pain; weight loss
      was noted in only 1 horse. The doses (2.0 to 4.6 mg/kg PO bid) and duration (5 to
      30 days) of administration of phenylbutazone were not unusually high relative to
      those recommended (4.4 mg/kg PO bid). Hypoproteinemia and hypoalbuminemia were
      observed in all horses at the time of admission; packed cell volume was low in 4
      horses, and hypocalcemia was also observed in 4 horses. Three of 5 horses (60%)
      appeared to respond to dietary management and discontinuation of administration
      of nonsteroidal anti-inflammatory drugs. Dietary management consisted of feeding
      pelleted feed, and restricting or eliminating roughage for a period of at least 3
      months. Two horses developed strictures of the right dorsal colon. One horse that
      developed a colonic stricture, possibly because its owners did not comply with
      recommendations for management, was subsequently treated surgically. The
      remaining horse that developed a stricture of the right dorsal colon was
      euthanized. These data indicate that some horses with right dorsal colitis can be
      successfully managed with medical treatment.

PMID- 8523326
TI  - Hemolytic transfusion reactions in a dog with an alloantibody to a common
      antigen.
AB  - Alloantibodies to high-frequency red cell antigens, defined as inherited traits
      occurring in 92% to 99% or more of the general population, are recognized as a
      cause of hemolytic transfusion reactions in humans. Here we describe a dog (dog
      erythrocyte antigen [DEA] 1.2- and DEA 4-positive) sensitized by prior blood
      transfusion, for which a compatible blood donor could not be found; transfusion
      of DEA 1.1-negative blood resulted in hemolytic transfusion reactions. Patient
      serum from days 1 (before first transfusion) and 16 was available for further
      testing; using 4 dogs with different blood types as potential donors, the major
      crossmatches were compatible using serum from day 1. However the crossmatches
      were all incompatible with serum from day 16, indicating that the patient was
      sensitized to an antigen after the first transfusion. The presence of an
      alloantibody against DEA 1.1 was not ruled out in this patient, but the
      incompatibility reactions of patient serum with red cells from donors negative
      for DEA 1.1 indicated that an alloantibody against a red cell antigen other than
      DEA 1.1 or any other known DEA for which typing reagents were available (DEA 3,
      5, and 7) was present. Subsequently, red cells from 1 of the patient's siblings
      (DEA 1.2-, 4-, and 7-positive) were found not to agglutinate when incubated with
      patient's serum from day 16, ruling out the presence of an anti-DEA 7 antibody,
      and suggesting that an alloantibody against a common red cell antigen missing in
      the patient and sibling was responsible for the blood incompatibility
      reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523327
TI  - Resolution of a left ureteral stone using electrohydraulic lithotripsy in a
      thoroughbred colt.
AB  - A 3-year-old Thoroughbred colt was presented for evaluation of azotemia and
      anorexia. Physical examination revealed a ureterolith in the left ureter,
      approximately 10 cm from the bladder, which was thought to obstruct urine flow by
      approximately 90% when viewed cystoscopically. Ultrasonographic examination of
      both kidneys revealed indistinct corticomedullary junctions, and the right kidney
      was more hyperechoic. A percutaneous biopsy of the right kidney revealed chronic
      interstitial nephritis with marked interstitial medullary fibrosis. Medical
      therapy consisting of IV fluids, sodium chloride PO, and ammonium chloride PO was
      initiated. Ureteroscopic electrohydraulic lithotripsy via a perineal urethrostomy
      was used to successfully remove the stone. Klebsiella oxytoca, which responded to
      oral enrofloxacin therapy, was cultured from the urine after surgery. Azotemia
      resolved and the horse resumed training.

PMID- 8523328
TI  - Platelet function defect in a 5-day-old Simmental calf.
AB  - A 5-day-old Simmental Heifer was evaluated for excessive bleeding from the skin
      following horse fly bites. A coagulation profile and platelet numbers were
      normal. In vitro platelet function, measured by whole blood aggregometry, was
      found to be abnormal when compared with age-matched controls. Therefore, this
      defect in hemostasis was attributed to a qualitative defect in platelet function.

PMID- 8523329
TI  - Clinical Vignette: Urachal abscess and cystitis in a calf.

PMID- 8523330
TI  - Quantitative acid base chemistry.

PMID- 8523331
TI  - What is the best source of useful data on the treatment of rheumatoid arthritis:
      clinical trials, clinical observations, or clinical protocols?

PMID- 8523332
TI  - An evidence based appraisal of the management of nontophaceous interval gout.

PMID- 8523333
TI  - Should patients with interval gout be treated with urate lowering drugs?

PMID- 8523334
TI  - Role of vascular endothelial growth factor in angiogenesis of rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the localization and role of vascular endothelial growth
      factor (VEGF), an endothelial cell specific mitogen, in rheumatoid arthritis
      (RA). METHODS: Immunohistochemical staining, reverse transcription polymerase
      chain reaction (RT-PCR) analysis and in situ hybridization for VEGF were
      performed on synovial tissues from 10 patients with RA, 5 patients with
      osteoarthritis (OA) and 3 autopsy cases. RESULTS: In RA, the proliferative ratio
      of synovial lining cells and vascular endothelial cells was significantly higher
      than that in OA and normal synovial tissues. Immunohistochemical staining
      demonstrated that VEGF polypeptide was strongly expressed in subsynovial
      macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells,
      and synovial lining cells, but not in vascular endothelial cells of patients with
      RA. On the other hand, in patients with OA and normal cases, VEGF polypeptide was
      slightly expressed in synovial lining cells and fibroblasts. RT-PCR showed a
      positive reaction for VEGF messenger RNA in RA, OA, and normal synovial tissues.
      A large number of subsynovial macrophages, fibroblasts, vascular smooth muscle
      cells, and synovial lining cells from patients with RA expressed VEGF mRNA using
      in situ hybridization. CONCLUSION: In RA, VEGF is synthesized and released by a
      large number of subsynovial macrophages, fibroblasts surrounding microvessels,
      vascular smooth muscle cells, and synovial lining cells and may stimulate
      endothelial proliferation in a paracrine manner via VEGF receptors.

PMID- 8523335
TI  - Treatment of rheumatoid joint inflammation with intrasynovial triamcinolone
      hexacetonide.
AB  - OBJECTIVE: To determine the effectiveness of intrasynovial triamcinolone
      hexacetonide coupled with joint rest (3 weeks upper extremity; 6 weeks lower
      extremity) in the treatment of joint and tendon sheath inflammation in patients
      with seropositive rheumatoid arthritis (RA). METHODS: The medical records of 169
      patients with seropositive RA treated by a single rheumatologist for at least one
      year between 1974 and 1992 were abstracted. RESULTS: Nine hundred fifty-six
      injections were given to 140 patients; approximately 75% of injected synovial
      structures remained in remission during a mean followup 7 years; 218 injections
      were given into previously treated structures. The injection rate was about 2 per
      patient in the first year, half of which were given at the time of the first
      visit. The rate then approximated 0.6 injections per patient-year for the next 15
      years. Joints in the right upper extremity were injected significantly (p = 0.01)
      more frequently than those on the left. CONCLUSION: Intrasynovial triamcinolone
      hexacetonide followed by rest is a very useful adjunctive modality in the
      treatment of seropositive rheumatoid arthritis.

PMID- 8523336
TI  - Combination drug therapy of seropositive rheumatoid arthritis.
AB  - OBJECTIVE: To determine the longterm morbidity and mortality in a cohort of 169
      patients with seropositive rheumatoid arthritis (RA) treated by a single
      rheumatologist with remittive agents used in combination. The effectiveness of a
      regimen combining pulse oral methotrexate, azathioprine and an antimalarial drug
      (MAH) was examined in detail. METHODS: All outpatient visits by patients followed
      for at least one year and up to 18 years (mean 7 years) were abstracted.
      Remittive antirheumatic drugs were used in combination to achieve progressive
      improvement. Univariate and multivariate analyses of the differences between
      first and last visit results in 9 process or outcome variables were calculated
      for the entire cohort, for those patients receiving or not receiving MAH at last
      visit, and for those patients taking methotrexate but not in combination with
      both azathioprine and an antimalarial. The numbers of patients in remission
      (Lansbury articular index zero), and near remission (articular index < 6) were
      determined for each of these groups. A survival curve was calculated. RESULTS:
      The entire patient cohort showed improvement in every variable except hemoglobin
      at the time of the last visit (p < 0.0004). On multivariate analysis MAH patients
      were improved only in American Rheumatism Association functional class compared
      to the other groups (p < 0.0001). Remission and near remission rates overall were
      43 and 61%; for MAH patients 45 and 69% (p = n.s.). Survival was no different
      from that of the general population. Herpes zoster (17 patients) and second
      attacks of varicella (2 patients) were the most striking side effects. Prednisone
      use was reduced from 34 to 19% of patients and the mean daily dose was lowered
      from 9.3 to 5.9 mg. CONCLUSION: Combination therapy with multiple antirheumatic
      agents successfully controlled joint inflammation in 167 of 169 patients with
      seropositive RA; complete remission was achieved in 43% of patients. Survival of
      this patient cohort did not differ from that of the general population.

PMID- 8523337
TI  - A preliminary evaluation of hydroxyurea for the treatment of rheumatoid
      arthritis.
AB  - OBJECTIVE: To obtain preliminary evidence on the safety and efficacy of low dose
      hydroxyurea as a treatment for rheumatoid arthritis (RA). METHODS: Five patients
      with active RA unresponsive to conventional therapy were entered into a 12 week,
      open label trial of hydroxyurea followed by a one month postdrug evaluation.
      RESULTS: Three of the 4 patients completing the study had a decrease in morning
      stiffness and number of swollen and tender joints. All 4 patients had a decrease
      in pain and an increase in function as measured by a modified health assessment
      questionnaire. No patient had improvement in sedimentation rate, C-reactive
      protein, or subjective measures of global well being. However, 3 of the 4
      patients had disease flare after the drug was withdrawn, demonstrated by
      increased number of swollen and tender joints. CONCLUSION: Low dose hydroxyurea
      may be effective in the treatment of RA, but confirmation will require further
      testing by a randomized double blind placebo controlled trial of patients with a
      broader spectrum of disease severity over a longer period of therapeutic
      intervention.

PMID- 8523338
TI  - Treatment of rheumatoid arthritis with platelet activating factor antagonist BN
      50730.
AB  - OBJECTIVE: To determine the efficacy and safety of a platelet activating factor
      (PAF) antagonist, BN 50730, in patients with rheumatoid arthritis. METHODS: Ten
      patients with an active disease were treated for 4 weeks with a PAF receptor
      antagonist, BN 50730, given orally (40 mg twice daily). The treatment period was
      followed by a 4 weeks followup period. RESULTS: Clinical indicators of disease
      activity significantly improved during the treatment period, with a progressive
      return to baseline values during the followup period. No significant change in
      laboratory variables was observed. The tolerance of the treatment was excellent,
      and no clinical or laboratory evidence of side effects was recorded. CONCLUSION:
      These results need to be confirmed in a controlled study, but suggest an
      antiinflammatory effect. PAF antagonists could represent a new class of
      therapeutic agents in inflammatory arthropathies.

PMID- 8523339
TI  - The second course of gold.
AB  - OBJECTIVE: To determine the outcomes in patients who receive more than one course
      of intramuscular gold therapy. METHODS: Gold clinic records of all patients who
      had received more than one course of gold at the Arthritis Centre, Vancouver,
      British Columbia were reviewed to extract clinical and laboratory data. RESULTS:
      Between 1949 and 1992, 1148 patients received injectable gold in the gold clinic
      of the Arthritis Centre, Vancouver, British Columbia. Forty-two patients received
      2 courses and 3 patients 3 courses of gold separated by intervals of greater than
      8 months. Twenty-one patients were markedly improved when the first course of
      gold was discontinued. Twenty of these 21 patients experienced a similar marked
      improvement from a 2nd course of gold. Three patients who received 3 courses had
      marked improvement with each course. Only 1 patient who experienced marked
      improvement with the first course of gold failed to respond to a 2nd course.
      CONCLUSION: In contrast to the published literature, our experience suggests that
      the response to the 2nd course of gold is similar to the response to the first in
      most patients with arthritis.

PMID- 8523340
TI  - How low can you go? Use of very low dosage of gold in patients with mucocutaneous
      reactions.
AB  - OBJECTIVE: We identified a group of patients with rheumatoid arthritis (RA) who
      were sensitive to both the beneficial and the side effects of intramuscular (im)
      gold treatment and whose disease was well controlled with doses of gold between 2
      mg every 6 weeks and 5 mg weekly. We describe the clinical course of these
      patients and their management aimed at maximizing the effectiveness of gold
      therapy. METHODS: Patients successfully treated with maintenance doses of im gold
      (< 20 mg/mo and not more than 10 mg/dose) were identified by chart review. Clinic
      records were reviewed to extract clinical and laboratory data. RESULTS: The
      population consisted of 11 female and 2 male patients with RA. Eleven were
      seropositive and 2 had Felty's syndrome. All developed mucocutaneous side effects
      within 20 weeks of beginning im gold therapy, at a time when RA had improved
      markedly compared to pretreatment status. Side effects recurred with sequential
      dosage adjustments so that doses > 10 mg were not tolerated. Side effects were
      managed by temporary discontinuation of gold until side effects resolved and
      resumption of treatment using usually 50% lower dosage. When side effects
      recurred the dosage was reduced further by 50%. Final maintenance dose was 2 mg
      every 4 weeks in 1 patient, 2 mg weekly in 1, 3 mg weekly in 3, 5 mg monthly in
      1, 10 mg every 3 weeks in 2, 10 mg every 4 weeks in 2, 10 mg every 6 weeks in 1,
      and 5 mg weekly in 2 patients. All patients improved and 6 are in complete
      remission. Mean duration of therapy was 5.5 yrs. CONCLUSION: The minimum
      effective dose of im gold is not known. Dose and dose intervals should be
      individualized for optimal benefits and tolerability.

PMID- 8523341
TI  - A longterm prospective study of the equipotency between deflazacort and
      prednisolone in the treatment of patients with polymyalgia rheumatica.
AB  - OBJECTIVE: The aim of the study was to establish the antiinflammatory equipotency
      between prednisolone and deflazacort. METHODS: Thirty patients with newly
      diagnosed polymyalgia rheumatica (PMR) were treated double blind with either
      prednisolone or deflazacort in a 12-month study. The initial daily dose was 20 mg
      prednisolone or 24 mg deflazacort. RESULTS: The clinical control of muscle pain
      was significantly inferior in the deflazacort group from 6 weeks to 3 months.
      Otherwise there was no difference in the clinical and biochemical variables. The
      ratio between antiinflammatory equipotent doses of deflazacort and prednisolone
      (mg:mg) stabilized at about 1.55 for the daily doses and about 1.40 for the
      cumulative doses. CONCLUSION: In PMR the antiinflammatory equipotency (mg to mg)
      between deflazacort and prednisolone was close to 1.40 (7:5 mg). Twenty mg
      prednisolone/day was fully sufficient to suppress symptoms in 94% of the
      patients.

PMID- 8523342
TI  - Divergent racial trends in mortality from systemic lupus erythematosus.
AB  - OBJECTIVE: To compare trends in mortality from systemic lupus erythematosus (SLE)
      between black and white females in the United States. METHODS: Analysis of
      nationwide cause of death data collected by the National Center for Health
      Statistics, 1968 to 1991. RESULTS: During the latter half of the 1968-91 period,
      trends in SLE mortality for black and white women under age 45 diverged and
      racial differences in total mortality from SLE widened. Among white females,
      total SLE mortality has been stable since the late 1970s at a mean annual rate of
      4.6 deaths per million. This stability results from a balance between declining
      risk among whites under age 45 and increasing in those beyond 55. Among blacks,
      total mortality has risen more than 30% since the late 1970s to a mean annual
      rate of 18.7 per million. This increase results from a combination of constant
      risk in black females under 45 and rising risk in women over 55. CONCLUSION:
      Trends for whites are consistent with a shift in mortality from younger to older
      women. This shift can be explained by longer postdiagnosis survival resulting
      from improved clinical management of SLE. The trends for blacks imply higher
      prevalence of SLE among black females than previously recognized and/or the
      existence of some impediment to young black females sharing in the full benefits
      of effective treatment.

PMID- 8523343
TI  - Autoantibodies in systemic lupus erythematosus and urticarial vasculitis.
AB  - OBJECTIVE: Urticarial vasculitis (UV) is both a primary disorder and a cutaneous
      vasculitic manifestation in patients with connective tissue diseases. We examined
      the prevalence of autoantibodies to vascular endothelial cells (aECA) and anti
      Clq antibodies in patients with UV. METHODS: ELISA were used to detect aECA and
      anti-Clq autoantibodies, and we tested for correlation with UV in 4 patient
      groups: healthy controls, patients with systemic lupus erythematosus (SLE) with
      and without UV, patients with primary systemic vasculitides with UV, and patients
      with hypocomplementemic urticarial vasculitis syndrome (HUVS). RESULTS: aECA were
      detected in 82% of patients with SLE with UV and 70% of patients with HUVS. In
      contrast, aECA were found in 32% of patients with SLE without UV and 14% of
      patients with primary UV. Anti-Clq antibodies were present in all patients with
      HUVS, but in < 20% in the other 3 groups. Antineutrophil cytoplasmic antibodies
      were detected in only one patient. CONCLUSION: Although the development of UV is
      likely to be multifactorial, the high prevalence of aECA in HUVS and SLE with UV
      suggests that this antibody is associated with vasculitis and may have a role in
      the pathogenesis of UV in these patients.

PMID- 8523344
TI  - Local cytokine expression in the progression toward B cell malignancy in
      Sjogren's syndrome.
AB  - OBJECTIVE: Sjogren's syndrome (SS) has been indicated as an ideal human model to
      investigate B cell lymphomagenesis. Our aim was to investigate similarities or
      differences in cytokine expression in both prelymphomatous and frank B cell
      lymphomatous SS lesions, as well as in SS related lesions versus SS unrelated
      malignant B cell non-Hodgkin's lymphomas. METHODS: The mRNA expression of
      interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-6, IL-6R, IL-9, IL-10, IL-12, tumor
      necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and transforming
      growth factor beta (TGF-beta) was analyzed by a sensitive reverse transcriptase
      polymerase chain reaction technique in 10 SS tissue samples from 10 consecutive
      patients [7 nonmalignant parotid myoepithelial sialadenitis (MESA) lesions with
      evidence of B cell clonal expansion, and 3 B cell non-Hodgkin's lymphomas] as
      well as a series of 11 SS unrelated B cell non-Hodgkin's lymphomas. RESULTS: IL
      1, IL-2, IL-3, IL-6, IL-6R, IL-10, IL-12, IFN-gamma, TNF-alpha, and TGF-beta mRNA
      was expressed in all or in the vast majority of the samples analyzed. IL-4 mRNA
      was detected in 2/3 SS related and in 3/11 SS unrelated non-Hodgkin's lymphomas,
      while SS related MESA samples were characterized by an IL-4 negative pattern and
      lacked IL-3 or IFN-gamma expression in 3/7 cases and in 2/7 cases, respectively.
      CONCLUSION: Many cytokines may be involved in the evolution of prelymphomatous to
      definite B cell malignant lesions in SS, as well as in the development of SS
      unrelated B cell non-Hodgkin's lymphomas. A putative pathobiological role of the
      IL-12/IL-4 balance, in the presence of cytokines that may sustain B cell
      proliferation (i.e., IL-3, IL-6, IL-10), may represent a major point for future
      research. Finally, our data reinforce the view of SS as a human model of B cell
      lymphomagenesis.

PMID- 8523345
TI  - Quantification of antiribosomal P0 protein antibodies by ELISA with recombinant
      P0 fusion protein and their association with central nervous system disease in
      systemic lupus erythematosus.
AB  - OBJECTIVE: Using solid phase ELISA with recombinant P0 fusion protein as the
      antigen for detecting antiribosomal P0 protein antibody, we analyzed the
      association of this antibody and anticardiolipin antibody (aCL) with central
      nervous system (CNS) disease in patients with active systemic lupus erythematosus
      (SLE). METHODS: Sera from 70 randomly selected Japanese patients with active SLE
      were assayed for IgG and IgM antiribosomal P0 protein antibody titers and IgG
      aCL. RESULTS: IgG and IgM antiribosomal P0 protein antibodies were present in 29
      and 12 (41.4 and 17.1%) of the 70 patients, respectively. The incidence of CNS
      disease, excluding lupus psychosis, was significantly higher in patients with IgG
      and IgM antiribosomal P0 protein antibodies than in those who lacked them (IgG
      antiribosomal P0 protein antibody 11/29 vs 3/41; IgM antiribosomal P0 protein
      antibody 7/12 vs 7/58). In addition, both IgG and IgM antiribosomal P0 protein
      antibody titers were significantly higher in patients with CNS disease, excluding
      lupus psychosis, than those without. No significant association was observed
      between antiribosomal P0 protein antibodies and lupus psychosis. No significant
      association was observed between IgG aCL and CNS disease. Serial studies of
      antiribosomal P0 protein antibodies and aCL in patients with transverse
      myelopathy also showed that IgG and IgM antiribosomal P0 protein antibodies, but
      not IgG aCL, were associated with CNS disease, excluding lupus psychosis.
      CONCLUSION: These data suggest a strong association of IgG and IgM antiribosomal
      P0 protein antibodies with CNS disease, excluding lupus psychosis, in SLE.

PMID- 8523346
TI  - Antibodies to fibrin bound tissue type plasminogen activator in systemic
      sclerosis.
AB  - OBJECTIVE: Abnormalities of tissue type plasminogen activator (tPA) and
      plasminogen activator inhibitor have been described in some patients with
      systemic sclerosis (SSc). We studied 128 unselected SSc sera for the presence of
      autoantibodies to fibrin bound tPA. METHODS: A solid phase fibrin-tPA immunoassay
      utilized 500 IU/ml tPA bound to solid phase fibrin. Sera diluted 1/50 were
      incubated with the fibrin bound tPA, the plates were washed, and bound
      immunoglobulins were detected using polyvalent peroxidase labelled goat antihuman
      immunoglobulins. Controls included plates coated with fibrin alone or tPA
      passively adsorbed to the plastic. Sera were considered positive when the
      A490/630 was above the mean + 2 SD (> 0.055) obtained with normal human serum in
      2 independent tests. RESULTS: 25/128 (20%) SSc sera demonstrated antibody
      reactivity with fibrin bound tPA (mean A490/630 = 0.112). Detailed clinical data
      were available on 117/128 patients with SSc and on 21/25 anti-tPA positive
      patients. The mean age of the anti-tPA positive group was 51 yrs and of the anti
      tPA negative group 49.6 yrs. Within the anti-tPA positive group there was a
      significantly higher proportion (p > 0.05) of patients with the CREST
      (calcinosis, Raynaud's esophageal dysmotility, sclerodactyly, telangiectasias)
      variant of SSc (7/25 = 28% vs 11/103 = 11%) and pulmonary hypertension (5/21 =
      24% vs 6/96 = 6%). CONCLUSION: Our study demonstrates that 20% of unselected
      patients with SSc have anti-tPA antibodies and that there is a higher
      representation of patients with CREST syndrome in this subgroup. The high
      frequency of pulmonary hypertension in the anti-tPA positive group suggests that
      these autoantibodies may play a pathogenic role in certain patients with SSc.

PMID- 8523347
TI  - A longitudinal study of anticardiolipin antibody in polymyalgia rheumatica and
      giant cell arteritis.
AB  - OBJECTIVE: To determine the incidence of elevated levels of anticardiolipin
      antibody (aCL) in patients with newly diagnosed polymyalgia rheumatica (PMR)
      and/or giant cell arteritis (GCA); and to determine the relationship between
      these antibodies at diagnosis and subsequent course of the disease over a period
      of 2 yrs. METHODS: Ninety-eight consecutive patients with PMR and/or GCA were
      examined for the presence of aCL, at presentation and every 6 mo for 2 yrs. Sixty
      four patients had PMR alone, 22 had coexistent PMR and GCA, and 12 presented with
      pure GCA. Patients presenting with suspected clinical diagnosis, overt or covert,
      of GCA were subjected to temporal artery biopsy from the symptomatic side within
      3 days of presentation. Appropriate serological, biochemical, and hematological
      investigations were undertaken at presentation and subsequently at times of
      periodic assessments. One hundred healthy age and sex matched elderly subjects
      were also screened for the presence of aCL as a control group. RESULTS: Elevated
      levels of aCL were detected in 20 patients at presentation. These included 9
      patients with PMR/GCA and 11 patients with pure PMR. During followup, 10 patients
      with pure PMR at presentation developed GCA. These comprised 5 of the 11 patients
      with high aCL at presentation and 5 of the 53 patients with normal levels of aCL
      at presentation. This was statistically significant with relative risk (4.82, 95%
      CI, 1.72-13.51) of developing GCA in the presence of PMR and a high aCL at
      presentation. Furthermore, 3 of the 5 patients with pure GCA and high aCL at
      presentation progressed to severe vascular complications (stroke, 2; anterior
      ischemic optic neuritis, 1) compared to none of the other patients in the study.
      Elevated levels of antineutrophilic cytoplasmic antibody were also analyzed and
      detected in only 4 patients, 3 with pure PMR and one with biopsy proven GCA.
      CONCLUSION: This prospective study suggests that a significant number of patients
      with PMR and/or GCA with elevated levels of aCL at presentation have increased
      risk of developing GCA or other major vascular complications. It is possible that
      aCL may be an independent prognostic marker for future vascular complications in
      patients with PMR and/or GCA.

PMID- 8523348
TI  - Synergistic cytotoxic effect of interferon-gamma and tumor necrosis factor-alpha
      on cultured human muscle cells.
AB  - OBJECTIVE: To investigate the effects of human interferon-gamma (IFN-gamma) and
      tumor necrosis factor-alpha (TNF-alpha), either alone or in combination, on the
      viability of human muscle cells in culture. METHODS: Cultures of human muscle
      cells were treated with various concentrations of recombinant IFN-gamma and TNF
      alpha alone and in combination, and the cytotoxic effects of the cytokines on
      muscle cells were assessed by measuring lactic dehydrogenase (LDH) release in
      supernatants and by observation of the cells for morphologic changes under phase
      microscopy. RESULTS: Exposure of muscle cells to 100 U/ml of either IFN-gamma or
      TNF-alpha for 9 days caused no cytotoxic effects, as assessed by LDH release in
      supernatants of muscle cell cultures and by microscopic observation of the cell
      cultures. However, when IFN-gamma and TNF-alpha were added together in the muscle
      cell cultures, they caused significant cytotoxic effects. Thus, in combination,
      IFN-gamma and TNF-alpha at 100 U/ml each caused significant release of LDH (3rd
      day 9%, 4th day 28.5%, 7th day 55.5%, 9th day 74%) in the supernatants of treated
      cultures compared to controls. Moreover, inspection by phase microscopy showed
      clear damage of muscle cells; from Days 3 to 4 progressive vacuolation,
      detachment of cells, and finally disintegration of the muscle cells by the 8th to
      10th day was observed. The synergistic cytotoxic effect of IFN-gamma and TNF
      alpha occurred at concentrations as low as 1 U/ml and 10 U/ml, respectively.
      CONCLUSION: Our study demonstrates for the first time a direct synergistic
      cytotoxic effect of IFN-gamma and TNF-alpha on human muscle cells in culture.
      Given that T cells and macrophages are prominent in the chronic inflammatory cell
      infiltrates of the affected muscles in patients with myositis, our findings
      suggest that IFN-gamma and TNF-alpha may play an important role in the
      pathogenesis of muscle destruction of this disorder.

PMID- 8523349
TI  - Total hip arthroplasty in patients with ankylosing spondylitis: longterm
      followup.
AB  - OBJECTIVE: To evaluate the longterm functional effects of total hip arthroplasty
      (THA) on 46 patients. METHODS: Clinical and radiographic examinations were
      performed on 46 patients (74 THA) with ankylosing spondylitis (AS). The mean
      followup period was 100 months (range 37-174 months); 32 hips were followed for
      more than 10 years. RESULTS: Significant benefit was obtained in pain control
      (all but 2) and function (mean improvement in range of motion 128 degrees) in the
      early stage so that patients could be gainfully employed. An average 100 months
      after THA, the overall functional results were rated excellent in 21 hips, good
      in 28, fair in 7, and poor in 18. Only 6 hips (8%) in our series developed
      clinically significant (Class III or IV) heterotopic ossification. Seventeen hips
      needed a 2nd operation because of loosening (11 hips), deep infection (3),
      malposition of acetabular component (2), and prosthetic failure (1). Another 6
      hips showed definite loosening on radiographs and needed to be revised. The total
      incidence of failure was 31% (23 hips). The average time from the index operation
      to loosening was 9.5 years (range 4-13 years). Factors contributing to component
      loosening were young age, short stature, and decreased postoperative range of
      motion. CONCLUSION: Total hip arthroplasty can be very important and beneficial
      to patients with AS, but the patients, being young and active, and with their
      rigid spines, do not treat their prostheses gently and are very dependent upon
      their mobility. They must be kept under supervision long after THA, probably for
      the rest of their lives, to identify possible longterm complications.

PMID- 8523350
TI  - Poststreptococcal reactive arthritis, clinical course, and outcome in 6 adult
      patients.
AB  - OBJECTIVE: To analyze the clinical course and laboratory features, as well as the
      outcome of 6 adult patients with articular manifestations, and evidence of
      streptococcal infection. METHODS: A retrospective review was performed of all
      patients seen in a rheumatology clinic at Louisiana State University Medical
      Center, with a diagnosis of poststreptococcal reactive arthritis (PSReA) to
      summarize the clinical features, laboratory findings, and clinical outcome
      between July 1991 and August 1994. RESULTS: Six patients were identified with
      PSReA. All had acute, severe inflammatory articular involvement that began
      shortly after a sore throat, with serological evidence of streptococcal
      infection, and accompanied by extraarticular clinical manifestations including
      glomerulonephritis and vasculitis, and poor response to aspirin and other
      nonsteroidal antiinflammatory drugs. In all cases the echocardiogram was
      negative, and on followup there was no evidence of cardiac involvement. In these
      patients antibiotic prophylaxis was not required. CONCLUSION: The clinical
      picture and serologic abnormalities exhibited by this group of patients suggest a
      diagnosis of PSReA rather than acute rheumatic fever. These cases also emphasize
      the resurgence of poststreptococcal infection related articular manifestations in
      our clinic population.

PMID- 8523351
TI  - Effects of continuous passive motion and immobilization on synovitis and
      cartilage degradation in antigen induced arthritis.
AB  - OBJECTIVE: To determine the effects of continuous passive motion (CPM) and
      immobilization on synovitis and cartilage degradation in an experimental model of
      chronic inflammatory, antigen-induced arthritis. METHODS: After bilateral
      arthritis induction of knee joints in 22 NZW rabbits, one knee was immobilized
      with a flexion splint while the opposite knee received CPM. RESULTS: After 2
      weeks (n = 10), the CPM treated knees had significantly greater joint swelling,
      synovial effusion, and histologic synovitis scores compared to its opposite
      immobilized knees. However, the total cartilage degradation score showed no
      statistically significant difference between the two treatments. When the
      treatments were discontinued after 2 weeks and animals were allowed intermittent
      active motion of both knees in cages for 4 weeks (n = 12), no statistically
      significant difference in joint swelling, synovial effusion, and histologic
      synovitis score was observed between the 2 treatments. The articular cartilage
      degradation, however, was significantly greater in the immobilized knees compared
      to its opposite CPM treated knees. Five of 12 immobilized knees had articular
      surface erosion compared to none in the CPM treated knees. Loss of cellularity
      was also significantly greater in the immobilized knees. CONCLUSION: Although CPM
      produced greater synovitis at 2 weeks, articular cartilage was better preserved
      in the knees treated with CPM than immobilization at 6 weeks.

PMID- 8523352
TI  - Complications of office based arthroscopy of the knee.
AB  - OBJECTIVE: To analyze the complication rates associated with office based
      arthroscopy in 2 community based rheumatology practices. METHODS: A retrospective
      analysis of 335 office based arthroscopy performed on 306 patients over a 35 mo
      period. All patients met specific clinical criteria to qualify for office based
      arthroscopy. Patients were followed postarthroscopy for a minimum of 12 weeks to
      assess the rates and types of complications. RESULTS: Of the 335 office based
      arthroscopies, 131 were diagnostic only, while 204 procedures were diagnostic and
      therapeutic. A total of 280 interventions were performed. Both major and minor
      complications were seen. The complication rates for major and minor events were
      1.2 and 12.8%, respectively. There was no mortality or longterm morbidity.
      CONCLUSION: Office based arthroscopy in patients with rheumatic diseases has a
      safety profile that compares favorably with arthroscopy performed in an
      ambulatory surgical center or operating room setting.

PMID- 8523354
TI  - Effects of synovial fluid hyaluronan concentration and molecular size on
      clearance of protein from the canine knee.
AB  - OBJECTIVE: The synovial fluid (SF) concentration of proteins (or fragments
      thereof) derived from the articular cartilage may reflect the processes of
      cartilage breakdown or repair within an arthritic joint and, hence, serve as a
      marker of these processes. Because changes in the clearance kinetics of marker
      molecules in SF would invalidate the assumption that their concentration in SF is
      directly proportional to turnover of the cartilage matrix, we investigated
      whether reduction in the concentration and/or molecular size of hyaluronan (HA)
      in joint effusions affects clearance of albumin from the canine knee. METHODS:
      The volume of distribution and clearance kinetics of radioiodinated serum albumin
      (RISA) were determined in normal dogs after injection of the knee with HA
      preparations whose concentration (3.0-0.03 mg/ml) and average molecular weight
      (0.2-6.1 x 10(6) Da) resembled those seen in synovial effusions, and which
      increased by roughly 270% the volume of fluid in the joint space. RESULTS: In
      knees injected with a physiologic concentration (3.0 mg/ml) of high molecular
      weight HA, the RISA distribution volume (2.8 ml) and clearance rate (1.7
      microliters/min) slightly exceeded those in knees in which the SF HA
      concentration was reduced 55-62% by injection of 0.3-0.03 mg/ml HA, but not those
      in knees in which the average molecular weight of the SF HA was reduced 84% by
      injection of exogenous HA with a molecular weight of 2.4 x 10(5) Da. CONCLUSION:
      Our data suggest that SF HA is a relatively minor determinant of the kinetics of
      RISA clearance from the joint, and the changes in HA content seen in joint
      effusions are unlikely to confound interpretation of the concentration of marker
      molecules in SF.

PMID- 8523353
TI  - Tenidap and flurbiprofen enhance uptake of matrix metalloproteinase inhibitor 4
      dedimethylaminotetracycline in inflamed joints of adjuvant arthritic rats.
AB  - OBJECTIVE: To identify a mechanism by which a matrix metalloproteinase (MMP)
      inhibitor might act synergistically with other agents to decrease MMP activity
      and thereby lessen the radiologic severity of adjuvant arthritis. METHODS: Rats
      with adjuvant arthritis were treated with either flurbiprofen (FBP) or tenidap
      (TDP), along with 4-dedimethylaminotetracycline (CMT-1), a potent MMP inhibitor.
      Indices of inflammatory severity and of radiologic destruction were assessed and
      compared to serum and bone levels of the MMP inhibitor. RESULTS: Combination
      therapy with the MMP inhibitor plus either of the other drugs led to synergistic
      improvement in radiologic severity. For example, CMT-1 combined with TDP reduced
      radiologic severity 45% while decreasing collagenase and gelatinase activities by
      61 and 72%, respectively, more than doubling bone CMT-1 levels (7.6 micrograms/g
      to 16.4 micrograms/g). FBP had similar effects. CONCLUSION: MMP inhibitors need
      access to the arthritic joint to interact with their target enzymes. Concomitant
      antiinflammatory therapy is required to assure drug entry into the inflamed
      tissues.

PMID- 8523355
TI  - Interleukin-4, an inhibitor of cartilage breakdown in bovine articular cartilage
      explants.
AB  - OBJECTIVE: To determine the ability of interleukin-4 (IL-4) to inhibit the
      degradation of proteoglycan in bovine articular cartilage explants stimulated by
      human interleukin-1 (IL-1 alpha), tumor necrosis factor (TNF-alpha), a
      combination of TNF-alpha and IL-1 alpha, and lipopolysaccharide (LPS). METHODS:
      35SO4 radiolabelled bovine radiocarpal cartilage explants were treated with IL-1
      alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS, plus various concentrations
      of IL-4 for 72 h. Proteoglycan released to the media was analyzed by
      scintillation counting and composite gel electrophoresis. Media samples were also
      analyzed by Western immunoblotting for metalloproteinases and TIMP. RESULTS: IL-4
      significantly reduced the cartilage proteoglycan degradation induced by IL-1
      alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS (50% inhibitory
      concentration, IC50 for IL-4 ranged from about 15 to 50 ng/ml). Western blotting
      showed that media stromelysin levels were increased by IL-1 alpha, TNF-alpha, and
      LPS, but that IL-4 had no observable effect. Composite gel electrophoresis
      demonstrated quantitative and qualitative differences in proteoglycan degradation
      after IL-4 treatment. CONCLUSION: IL-4 has a potent inhibitory effect on
      cartilage degradation after stimulation with IL-1 alpha, TNF-alpha, TNF-alpha
      plus IL-1 alpha, or LPS. These results suggest that IL-4 should be investigated
      further for therapeutic value as a chondroprotective agent for the treatment of
      arthritis.

PMID- 8523356
TI  - Osteoarthritis in rhesus macaque knee joint: quantitative magnetic resonance
      imaging tissue characterization of articular cartilage.
AB  - OBJECTIVE: To assess cartilage matrix quality variation by anatomical location
      and extent of osteoarthritis (OA) using quantitative magnetic resonance imaging
      (MRI) and to compare the anatomic MR morphologic features with corresponding
      histological findings. METHODS: We studied 18 fully encapsulated right knee
      joints from a population of rhesus monkeys with a high incidence of degenerative
      arthritis resembling human OA. Relaxation times (T1 and T2) spin density, and
      cartilage thickness were determined along 8 contiguous anteroposterior segments
      of articular cartilage. Histological slides, prepared in the same plane as the MR
      image, were assessed for OA severity. Using a modification of Mankin's OA
      classification, each quadrant was grouped into normal (0), mild (1), moderate
      (2), or severe OA (3). Histopathological scores served as the standard and
      corresponding MR quadrants were classified accordingly. RESULTS: Cumulative
      results revealed a significant decrease in T1 relaxation time (p = 0.04) and an
      increase in T2 relaxation time (p = 0.03) in the mild and severe OA groups,
      respectively. Statistically significant changes in spin density and cartilage
      thickness measurements were not observed. MR signal intensity abnormalities in
      selected regions of interest were demarcated and studied histologically. Regions
      with histological proliferating chondrocytes or fibrillated cartilage showed
      bright signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and corresponded
      with elevated T1 and T2 values. Histological regions of collagen condensation
      showed low signal intensity on MR images (TR = 3000 ms; TE = 10 ms) and
      corresponded with decreased T1 and T2 relaxation times. CONCLUSION: Topological
      quantitative MRI relaxation time assessment demonstrates increasing cartilage
      matrix quality variation with OA progression.

PMID- 8523357
TI  - The treatment of osteoarthritis of the knee with pulsed electrical stimulation.
AB  - OBJECTIVE: The safety and effectiveness of pulsed electrical stimulation was
      evaluated for the treatment of osteoarthritis (OA) of the knee. METHODS: A
      multicenter, double blind, randomized, placebo controlled trial that enrolled 78
      patients with OA of the knee incorporated 3 primary efficacy variables of
      patients' pain, patients' function, and physician global evaluation of patients'
      condition, and 6 secondary variables that included duration of morning stiffness,
      range of motion, knee tenderness, joint swelling, joint circumference, and
      walking time. Measurements were recorded at baseline and during the 4 week
      treatment period. RESULTS: Patients treated with the active devices showed
      significantly greater improvement than the placebo group for all primary efficacy
      variables in comparisons of mean change from baseline to the end of treatment (p
      < 0.05). Improvement of > or = 50% from baseline was demonstrated in at least one
      primary efficacy variable in 50% of the active device group, in 2 variables in
      32%, and in all 3 variables in 24%. In the placebo group improvement of > or =
      50% occurred in 36% for one, 6% for 2, and 6% for 3 variables. Mean morning
      stiffness decreased 20 min in the active device group and increased 2 min in the
      placebo group (p < 0.05). No statistically significant differences were observed
      for tenderness, swelling, or walking time. CONCLUSION: The improvements in
      clinical measures for pain and function found in this study suggest that pulsed
      electrical stimulation is effective for treating OA of the knee. Studies for
      longterm effects are warranted.

PMID- 8523358
TI  - An assessment of the needs of family physicians for a rheumatology Continuing
      Medical Educational program: results of a pilot project.
AB  - OBJECTIVE: To assess the needs and determine the effect of a Continuing Medical
      Education (CME) program designed for primary care physicians on the management of
      osteoarthritis (OA). METHODS: The needs of potential CME consumers were
      determined using a standardized case recall questionnaire on the management of
      OA. A CME program was designed to specifically address identified needs, and the
      effect of the program was determined by repeat questionnaire by participants at 3
      mo followup. RESULTS: Primary care physicians had a high rate of use of
      nonsteroidal antiinflammatory drugs (NSAID) and a proportionately low rate of use
      of analgesics. Physiotherapeutic modalities and local steroid injections were
      underused. There was a relatively low appreciation of potential side effects of
      therapeutic choices and possible risk factors for toxicity. After participating
      in the CME program, attendees demonstrated change in their therapeutic practices
      with an increased awareness of relative risks/benefits of NSAID vs analgesics.
      CONCLUSION: A case recall questionnaire format is a simple and inexpensive means
      of determining the need for developing a specific program for, and determining
      the effect of a CME program applicable to rheumatology CME activities for primary
      care physicians.

PMID- 8523359
TI  - Fatal pulmonary fibrosis complicating low dose methotrexate therapy for
      rheumatoid arthritis.
AB  - We report the fatal disease course of 2 aged patients with rheumatoid arthritis
      (RA). Both had respiratory complaints after 10-15 weeks of treatment with
      methotrexate (MTX). After withdrawal of MTX, and despite the use of
      corticosteroids and ventilatory support, both died of respiratory failure. Post
      mortem examination showed extensive pulmonary fibrosis, bronchiolitis obliterans,
      and hyperplasia of type II pneumocytes. To our knowledge, this is the first
      report of fatal pulmonary fibrosis following short courses of low dose MTX
      therapy for RA.

PMID- 8523360
TI  - Intravascular malignant lymphoma ("malignant angioendotheliomatosis") mimicking
      primary angiitis of the central nervous system.
AB  - Malignant angioendotheliomatosis is characterized by the plugging of central
      nervous system blood vessels with large mononuclear cells, thus mimicking primary
      angiitis of the central nervous system. When autoantibodies are present, it can
      mimic connective tissue disease. Treatment of malignant angioendotheliomatosis
      with cytoxan may prolong survival.

PMID- 8523361
TI  - Cauda equina compression by epidural lipomatosis in obesity. Effectiveness of
      weight reduction.
AB  - Epidural lipomatosis (EL) is characterized by abnormal accumulation of
      unencapsulated fat in the epidural space, and usually occurs as a complication of
      longterm steroid therapy. This condition, which may result in devastating
      neurologic complications, has also been reported without exogenous steroid
      intake. We describe a case of nonsteroid induced symptomatic EL associated with
      obesity, and emphasize the possibility of effective medical management of this
      entity with weight reduction instead of decompressive laminectomy whenever
      neurologic symptoms are mild and stable.

PMID- 8523362
TI  - Emphysematous septic arthritis: case report and review of the literature.
AB  - We describe a patient with Escherichia coli infectious arthritis associated with
      intraarticular emphysema. The implications of this finding and previous
      experience with this entity are reviewed.

PMID- 8523363
TI  - The validity of radiography as outcome measure in rheumatoid arthritis.
AB  - Radiographic imaging of hand (and foot) joints is regarded as one of the gold
      standards of outcome for rheumatoid arthritis. Outcome can be defined as
      suffering or loss of health caused by the disease process, and process as the
      abnormal physiological consequences that follow from the cause of the disease. By
      these definitions and through a review of validity components, I propose that
      radiographic damage may be best viewed as a unique and important measure of past
      process, and possibly as a proxy for outcome.

PMID- 8523364
TI  - Assessment of radiographic abnormalities in rheumatoid arthritis: what have we
      accomplished and where should we go from here?
AB  - Assessment of radiographic damage in rheumatoid arthritis (RA) by scoring methods
      is useful to describe the progression of disease, and is an objective method of
      determining the effects of treatment. The history of the development of
      radiographic scoring methods is reviewed. None is ideal or truly quantitative and
      better methods are needed. Features of an ideal method are presented and the
      results of assessing treatment of RA by current methods of radiographic scoring
      are reviewed. Suggestions are made regarding the design of future therapeutic
      trials to take advantage of study features most likely to yield conclusive
      results by radiographic outcome assessment.

PMID- 8523365
TI  - Radiographic progression on radiographs of hands and feet during the first 3
      years of rheumatoid arthritis measured according to Sharp's method (van der
      Heijde modification).
AB  - OBJECTIVE: To determine the development rate of erosions and joint space
      narrowing in a cohort of patients during the first 3 years of rheumatoid
      arthritis (RA). METHODS: All consecutive patients fulfilling the American
      Rheumatism Association criteria and seen within the 1st year of the disease were
      followed prospectively with biannual radiographs of hands and feet. One hundred
      and forty-seven patients were followed for 2 years and 90 patients for 3 years.
      Erosions and joint space narrowing were scored with a modified version of Sharp's
      method (van der Heijde modification). Wilcoxon's rank sum test was used to test
      differences between joints and between erosions and joint space narrowing.
      RESULTS: On average, at 3 year followup most groups of joints showed about 8% of
      the maximum possible score. In most groups of joints about 20% of the joints were
      affected. At the start more foot joints were affected than hand joints. However,
      the increase in the number of affected joints and in the radiographic damage was
      similar in hands and feet. Consequently, the predominance of affected foot joints
      was still present after 3 years. The progression in the 3rd year was
      statistically significantly less compared to the 1st year. This was more
      pronounced for the number of affected joints than for radiographic damage.
      CONCLUSION: We found that 70% of the patients showed radiographic damage after 3
      years and this group could already be selected after 1 year. Overall, +/- 18-20%
      of the joints were affected after 3 years, with relatively few abnormalities per
      joint (+/- 8% of the maximum possible score was reached). The rate of progression
      in the 1st year was significantly more than in the 2nd and 3rd years, indicating
      a flattening of the curve of radiographic progression.

PMID- 8523366
TI  - Radiographic progression in rheumatoid arthritis: results of 3 comparative
      trials.
AB  - In 3 clinical trials the effects of 6 different disease modifying antirheumatic
      drugs on radiographic progression were evaluated. Despite the wide range in
      disease duration of patients in the different studies, a statistically
      significant slowing of radiographic progression was found in those patients
      treated with aurothioglucose, sulfasalazine, and methotrexate compared to
      auranofin, hydroxychloroquine, and azathioprine, respectively. These drugs might
      therefore be considered as disease controlling antirheumatic drugs.

PMID- 8523367
TI  - Attempts to apply curve fitting models to the analysis of progression of
      radiographic damage in rheumatoid arthritis are laudable, but are the results
      believable?

PMID- 8523368
TI  - Influenza vaccination in rheumatoid arthritis.

PMID- 8523369
TI  - Successful treatment of agranulocytosis and sepsis with granulocyte colony
      stimulating factor in a case of Felty's syndrome.

PMID- 8523370
TI  - Hydrarthrosis of the knee or ankle revealing metaphyseal stress fractures of the
      tibia. A report of 3 cases.

PMID- 8523371
TI  - Cold induced complement activation in hepatitis C virus associated vasculopathy.

PMID- 8523372
TI  - Dietary calcium and blood pressure: a review of the observational studies.
AB  - The objective of this study was to assess whether the epidemiological data
      support a relation between dietary calcium intake and blood pressure (BP). Fifty
      three published reports of observational studies relating intake of calcium or
      calcium-rich foods to BP in the USA (n = 33), Canada (n = 3), Puerto Rico (n =
      1), Europe (n = 9), Asia (n = 5), Australia (n = 1) and South Africa (n = 1) were
      identified including a Medline search (January 1983-November 1993). Sample size
      ranged from 55 to over 58,000 (median 885). Five studies were prospective, 48
      cross-sectional, of which four also contained a longitudinal component. Various
      dietary methodologies were used; the most common was the 24 h dietary recall.
      Most studies controlled for age, sex and body mass index, with variable control
      for other confounders. Many reports also allowed identification of subgroups by
      sex, age and race. One hundred and eight population samples and subgroups could
      then be identified. There was inconsistency in results both within and between
      studies. In 12 of the 53 published reports simple regression coefficients were
      reported. Median regression coefficients were -0.033 mm Hg/100 mg Ca (range -4.90
      to +/- 0.47; n = 12) for systolic blood pressure (SBP) and -0.140 mm Hg/100 mg Ca
      (range -9.40 to +1.63; n = 10) for diastolic blood pressure (DBP). The
      association between dietary calcium intake and BP could not be assessed in all
      108 population samples and subgroups because of design features, incompleteness
      of reported results and methods of analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523373
TI  - End-organ damage in treated severe hypertension: close relation to nocturnal
      blood pressure.
AB  - In an attempt to improve therapeutic decision-making in severe hypertension,
      different blood pressures (BP) were correlated with target organ damage in a
      cross-sectional study of 20 asymptomatic patients. Casual BP was 197/117 (s.d.
      31/10) mmHg despite therapy. Each subject was assigned an end-organ score on the
      basis of the number of silent cerebrovascular damages detected by magnetic
      resonance imaging, funduscopic retinopathy, cardiac hypertrophy by
      echocardiography, and renal involvement evaluated by isotopic renography. The
      pooled scores for target organ damage showed significant correlations with an
      elevated asleep mean ambulatory (amb-) brachial systolic (r = 0.84) and diastolic
      BP (r = 0.88) but not with either awake amb-BP (means or peak values), causal BP
      or invasive radial BP at the clinic. Night-time amb-DBP increased with age in
      contrast to the daytime DBPs. Furthermore, the nocturnal fall in mean arterial
      amb-BP was significantly less in patients aged > or = 60 years, average 5%, than
      in patients < 60 years, 16%. This may have prognostic implications even if, after
      age adjustment, the inverse relation (r = -0.78) between the end-organ scores and
      the dip in BP did not reach independent significance. The close association of
      cardiovascular complications with night-time rather than daytime BP emphasises
      the importance of making a prospective study in this field, trying to optimise
      the nocturnal BP in severe hypertension.

PMID- 8523374
TI  - Office and ambulatory blood pressure: a comparison between amlodipine and
      felodipine ER. Danish Multicentre Group.
AB  - The anti-hypertensive efficacy and safety of extended-release (ER) felodipine (5,
      10 or 20 mg) and amlodipine (5 or 10 mg) once daily were compared in patients
      with mild-to-moderate essential hypertension in a double-blind, double-dummy,
      randomised, comparative study. A total of 118 patients were allocated to a 12
      week, double-blind treatment with either felodipine ER (n = 57) or amlodipine (n
      = 61). The anti-hypertensive effect was evaluated by measuring office blood
      pressure (BP) at baseline and after 4, 6, 8 and 12 weeks, together with 24 h
      ambulatory blood pressure monitoring (ABPM) at baseline, on day 1 of treatment
      and at the end of the study. The mean office BP changes from baseline to week 12
      were -13.4 (+/- 15.7)/-11.8 (+/- 6.9) mmHg for felodipine ER (mean daily dose
      11.2 mg) and -15.3 (+/- 17.0)/-12.9 (+/- 7.3) mm Hg for amlodipine (mean daily
      dose 7.4 mg). All BP reductions were significant (P < 0.01) with respect to time,
      but differences between treatment groups were not significant. The mean
      ambulatory BP changes from baseline to end of the study were -11.6 (+/- 5.2)/
      10.0 (+/- 2.0) mmHg for felodipine ER and -16.3 (+/- 4.4)/-9.6 (+/- 3.0) mm Hg
      for amlodipine, both significant (P < 0.01). The fall in ambulatory SBP was
      significantly greater (P < 0.001) in the patients treated with amlodipine
      compared with felodipine ER whereas there was no difference between the groups
      with respect to ambulatory DBP. Both drgs were well tolerated with a withdrawl
      rate of 12% equally distributed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523375
TI  - Twenty four-hour ambulatory blood pressure monitoring in women with pre
      eclampsia.
AB  - The aim of our study was to evaluate by means of ambulatory 24 h monitoring the
      diurnal systolic (SBP) and diastolic (DBP) blood pressure profiles in a group (n
      = 18) of gravid patients with pre-eclampsia compared with a group (n = 17) of
      healthy control subjects matched for age and week of gestation to assess whether:
      (i) ambulatory BP is also raised in pre-eclampsia; (ii) the increase of BP, if
      present, occurs to the same extent during both daytime and night; and (iii) a
      blunted BP pattern is consistently present in pre-eclampsia. BP was recorded at
      intervals of 15 min for 25 h using a TM2420 non-invasive pressurometer. The
      presence of a circadian rhythm of BP was assessed by cosinor analysis. SBP was
      higher in women with pre-eclampsia (24 h average 115 +/- 11 vs. 136 +/- 12, P = 6
      x 10(-6); daytime 117 +/- 12 vs. 139 +/- 13, P = 6 x 10(-6); night 110 +/- 11 vs.
      129 +/- 14, P = 5 x 10(-5) as well as DBP (24 h average 67 +/- 5 vs. 86 +/- 6, P
      = 8 x 10(-12); daytime 69 +/- 6 vs. 89 +/- 5, P = 2 x 10(-11); night 62 +/- 4 vs.
      80 +/- 8, P = 5 x 10(-10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523376
TI  - Case-control study of maternal blood group and severe pre-eclampsia.
AB  - The relation of maternal blood group to pre-eclampsia has not been adequately
      studied in previous research. To investigate this relation, we conducted a case
      control study of primigravidae. Data on 204 consecutive severely pre-eclamptic
      patients delivered pre-term and 744 controls were analysed using multivariate
      methods. After adjustment for the confounding effects of maternal age, social
      class, origin, education, pre-pregnancy weight and body mass index, and weight
      gain in pregnancy, we found an increased risk of pre-eclampsia for mothers with
      blood type AB (adjusted odds ratio = 3.07; 95% confidence interval 1.48-6.36).
      With respect to blood group O, A, B and Rh type, no statistically significant
      correlation with severe pre-eclampsia was found. Although these results should be
      considered with caution, they support the hypothesis of a linkage mechanism
      involving blood group in the inheritance of susceptibility to pre-eclampsia.

PMID- 8523377
TI  - Compliance of the digital artery is decreased in patients with essential
      hypertension.
AB  - The compliance of the arterial vascular system is decreased in hypertensive
      subjects. On the other hand, the vessel wall properties such as compliance depend
      on blood pressure (BP). The aim of the present study was to determine the
      compliance of the digital arteries and to test the hypothesis that decreased
      compliance is either caused by a downward shift of the compliance-pressure
      relation or, alternatively, by a change in the compliance-pressure relation
      itself. We used impedance plethysmography and a finger BP measuring device to
      determine beat-to-beat the pressure-pulse amplitude (delta P), the volume-pulse
      amplitude (delta V) and the compliance from digital arteries of 10 hypertensive
      patients and 10 similarly aged normal subjects. The mean local blood pressure
      (MLBP) in the digital arteries was changed by vertically varying the position of
      the right hand in relation to the heart. The compliance of the digital arteries
      in hypertensive patients (2.76 microliters/mm Hg per 100 ml tissue) is
      significantly (P < 0.05) decreased compared with that in normal subjects (4.03
      microliters/mm Hg per 100 ml tissue). A reduction of MLBP by 50 mm Hg leads to an
      increase of compliance in normotensive subjects from 4.03 to 12.68 microliters/mm
      Hg per 100 ml tissue but in hypertensive patients only from 2.76 to 6.16
      microliters/mm Hg per 100 ml tissue. The slope of the curve in the low pressure
      range was also markedly decreased in hypertensive patients compared with
      controls. We conclude, that the compliance-pressure relation is not merely
      shifted but also extensively alterated in hypertensive patients.

PMID- 8523378
TI  - Myocardial trophic effects of blood pressure in children with insulin-dependent
      diabetes mellitus.
AB  - To evaluate the effect of blood pressure (BP) on the left ventricular mass index
      (LVMI), 66 children with IDDM 13 +/- 3 years of age were studied and compared
      with 58 healthy age-matched siblings. The 24 h BP recordings disclosed that
      children with diabetes had higher DBP (68 vs. 65 mm Hg, P = 0.002), especially at
      night (60 vs. 55 mm Hg, P = 0.00007), with a minimisation of the normal nocturnal
      hypotension (-9.9 vs. -12.4 mm Hg, P = 0.04). Their LVMI was higher (79 vs. 71
      g/m2, P = 0.02); it was independent of BP values and variability (P = NS), but it
      was positively correlated with heart rate (r = -0.46, P = 0.0005). In the control
      group, LVMI was significantly correlated with the mean SBP (r = 0.46, P =
      0.0005); with its variability (r = 0.32, P = 0.02) and, to a lower extent, with
      heart rate (r = -0.29, P = 0.03). It is concluded that in children with diabetes
      mellitus the participation of BP in myocardial hypertrophy is not so obvious,
      although the BP load is increased. The increase of the LVMI occurs early in life
      and before the onset of hypertension.

PMID- 8523379
TI  - Comparison of amlodipine and quinapril on ambulatory blood pressure and platelet
      function in hypertension.
AB  - The effect of calcium channel blocker (CCB), amlodipine (5-10 mg/day) and
      angiotensin-converting enzyme (ACE) inhibitor, quinapril (10-40 mg/day) on
      ambulatory blood pressure (ABP), rheological and platelet function in
      hypertension were compared in this randomised double-blind placebo-controlled
      cross-over study. This study was preceded by 4 weeks placebo run-in period and
      the total duration of the study was 28 weeks. Casual and 24 h ABP, plasma renin
      activity (PRA) and plasma aldosterone (PA) concentration as well as metabolic and
      platelet function were determined before and at the end of each drug therapy. A
      total of 27 patients completed this study. Casual BP was significantly reduced
      after amlodipine or quinapril treatment, but there was no change in heart rate.
      Regarding the 24 h ABP, amlodipine produced a fall from 145 +/- 8/94 +/- 7 to 130
      +/- 13/85 +/- 10 mm Hg (P < 0.001 for both SBP and DBP). Quinapril also caused a
      reduction from 144 +/- 10/94 +/- 7 to 134 +/- 12/88 +/- 8 mm Hg (P < 0.001 for
      both SBP and DBP). Neither amlodipine nor quinapril produce any significant
      change in heart rate. The level of 6-keto-prostaglandin Fl alpha (6-Keto-PGFl
      alpha) was increased from 36.8 +/- 4.4 to 45.1 +/- 2.5 pg/ml (P < 0.05) and no
      significant change of thromboxane B2(TXB2) was noted after amlodipine treatment.
      PRA was increased from 1.24 +/- 0.31 to 1.62 +/- 0.41 ng/ml/h (P < 0.05) after
      quinapril treatment. Other biochemical parameters were unchanged.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8523380
TI  - Proceedings of the 6th Annual Symposium of the London Hypertension Society. 14
      March 1995.

PMID- 8523381
TI  - Confocal microscopy for structure and real-time pharmacology in blood vessels.
AB  - The structure and composition of living small blood vessels can be studied in
      great detail in three dimensions using confocal microscopy. Individual cells and
      their components can be visualised by vital dyes for the nucleus, cytoplasm or
      extracellular space. Specific ligands can then localise individual components
      such as membrane receptors with great precision. Cell function is unaffected,
      allowing the study, in real time, of the changing relation and contribution to
      vascular contraction or dilatation of different cell types particularly smooth
      muscle, endothelium and adventitia. This allows not only visualisation but
      quantification, using image analysis software. These techniques will be of
      particular value in assessing the contribution of form to function in
      pathological situations such as vascular remodelling in hypertension.

PMID- 8523382
TI  - Fetal influences on adult hypertension.
AB  - Studies of population samples of adults and children consistently show a relation
      between lower birthweight and higher subsequent blood pressure (BP). This
      relation is not present in the neonatal period or in adolescence, which may
      reflect the unusual dynamics of growth at these times. We suggest that the
      inverse relation of BP with birthweight is a result of fetal adaptations to an
      adverse environment, particularly undernutrition. In making these adaptations,
      long-term physiology or metabolism is changed in a way that leads to subsequent
      higher BP. Such changes may be in the structure of blood vessels, or the re
      programming of influential hormonal axes, such as the pituitary adrenal axis.

PMID- 8523383
TI  - Might non-pharmacological treatment disadvantage patients with hypertension?
AB  - Weight reduction, moderate salt restriction and alcohol reduction are effective
      in lowering blood pressure (BP), and are feasible interventions for long-term
      management of hypertension. When used in combination these non-pharmacological
      measures are significantly inferior to drug therapy in anti-hypertensive effect.
      When they are implemented as a first step in the treatment of mild hypertension,
      resorting to drug therapy only if non-pharmacological measures fail, anti
      hypertensive drugs can be avoided in about 40% of patients. However, BP control
      is again significantly inferior with this strategy compared with drug therapy
      without non-pharmacological advice. Those given advice on non-pharmacological
      measures may therefore have suboptimal protection against cardiovascular
      complications. This is particularly so when the threshold for drug treatment is
      set at a DBP of > or = 100 mmHg, as many patients will be left untreated with
      DBPs between 90 and 99 mm Hg as a result of non-pharmacological measures. Non
      pharmacological treatment may thus stand between patients and anti-hypertensive
      drug therapy, which nowadays is simple, well-tolerated, safe and proven effective
      in preventing cardiovascular disease. The role of non-pharmacological therapy
      needs to be reconsidered.

PMID- 8523384
TI  - Two new culprits in cardiovascular disease: QT dispersion and aldosterone.
AB  - Two new culprits have arisen in chronic heart failure (CHF). QT dispersion, which
      is the maximum QT interval minus the minimum QT interval in an ECG, may well
      predict sudden cardiac death. Aldosterone produces many harmful effects:
      magnesium loss, myocardial fibrosis, sympathetic activation, baroreflex
      dysfunction and ventricular arrhythmias. The RALES study is currently examining
      whether spironolactone improves mortality in CHF.

PMID- 8523385
TI  - New ideas for treating hypertension.
AB  - Despite the wide range of anti-hypertensive drugs currently available many more
      are being developed, including entirely novel classes of compounds. This is not
      entirely surprising as a minority of patients do not respond to existing agents
      or are unable to tolerate them at therapeutic doses. It is also true that
      hypertension represents a very large international market. This brief review
      deals with the following classes of agents which are at various stages of
      development: (1) angiotensin receptor antagonists of the AT1 subtype, the first
      of which has recently been marketed in the UK; (2) renin inhibitors, whose
      development has been hindered by the poor bioavailability of all but the most
      recent compounds; (3) imidazoline (I1) receptor agonists, centrally acting drugs
      with relatively little sedating activity; (4) potassium channel openers, which
      act as potent vasodilators; (5) neutral endopeptidase inhibitors which potentiate
      the actions of atrial natriuretic peptides; and (6) endothelin antagonists, which
      are still in pre-clinical development. The potential clinical significance of
      these compounds is discussed.

PMID- 8523386
TI  - Absence of genetic linkage between polymorphisms of the insulin receptor gene and
      essential hypertension.
AB  - This study evaluated whether hypertensive siblings had excess sharing of RsaI and
      SstI alleles of the insulin receptor gene compared with a random population.
      Thirty families consisting of 60 affected individuals with established
      hypertension were genotyped for the RsaI and SstI restriction fragment length
      polymorphisms and the resulting genotype data was analysed using the affected
      pedigree member method of linkage analysis. The hypertensive siblings were found
      to have increased sharing of INSR alleles; however, this linkage could not be
      confirmed using a maximum LOD score method. Thus, the results from this study do
      not support a role for the INSR gene in the genesis of essential hypertension in
      the population studied.

PMID- 8523387
TI  - Association of angiotensin converting enzyme DD genotype with hypertension in
      diabetes.
AB  - Angiotensin converting enzyme (ACE) genotypes have been associated with
      hypertension in the general population. However, the relation of ACE genotype to
      the prevalence of hypertension in diabetic populations is less clear. This study
      investigated ACE genotypes in 100 patients with diabetes mellitus, of whom 41
      were on anti-hypertensive medication. A significant association was found between
      the presence of the ACE-D allele and hypertension in both the overall diabetic
      group (D = 0.66, P < 0.01) and in the subset of diabetics who had non-insulin
      dependent diabetes (D = 0.69, P < 0.001). There was no correlation of ACE
      genotype with hypertension in insulin-dependent diabetes (D = 0.57).

PMID- 8523388
TI  - Proportion of patients with isolated systolic hypertension who have burned-out
      diastolic hypertension.
AB  - In a community survey of 3242 subjects, 1663 did not initially have isolated
      systolic hypertension (ISH) and were re-screened an average of 8 years later. ISH
      developed in 53 (22%) of untreated patients with previous diastolic hypertension.
      Similarly, 8% of subjects with transient hypertension and 8% of normotensive
      controls developed ISH. Of all cases of ISH, 16% had previous diastolic
      hypertension. These subjects were more likely to have continued to smoke (P =
      0.01) and lost more weight (P = 0.001) than patients with ISH who did not have
      burned-out diastolic hypertension.

PMID- 8523389
TI  - TGF-beta: implications for human vascular disease.

PMID- 8523390
TI  - Lack of association between angiotensinogen polymorphism (M235T) and
      cerebrovascular disease and carotid atheroma.
AB  - Genetic influences in cerebrovascular disease (CVD) may act either independently
      or by predisposing to, or modulating, the effect of risk factors such as
      hypertension. Factors involved in the pathogenesis of atherosclerosis, thrombosis
      and vasoconstriction are important in CVD. The angiotensinogen gene has recently
      been linked with essential hypertension in affected sibships and a particular
      polymorphism in exon 2 of the angiotensinogen gene, a threonine to methionine
      substitution at position 235 (M235T), has been associated with pre-eclampsia and
      hypertension. In this study we examined the relation of M235T polymorphism to
      cerebrovascular disease and carotid atheroma in 100 consecutive Caucasian
      patients with internal carotid artery territory ischaemia (TIA or stroke),
      presenting to a carotid ultrasound service. Forty five age-matched controls
      (mostly patients' spouses) were also studied. Hypertension was defined as current
      treatment with anti-hypertensive agents, or SBP > 160 mm Hg or DBP > 95 mm Hg.
      Twelve of 100 cases (12%) and eight of 45 controls (12%) were homozygous for the
      T235 allele. T:M allele ratios were 0.34:0.66 in cases and 0.34:0.66 in controls.
      There was no relation between the polymorphism and either internal carotid
      stenosis or common carotid artery intima-media thickness. In the cases, mean
      percentage internal carotid artery stenosis was TT 18.3 (SD 18.7)%, MT 38.0
      (27.1)% and MM 36.8 (30.2)%. Mean intima-media thickness was TT 0.87 (0.18) mm,
      MT 0.95 (0.34) mm and MM 0.88 (0.23) mm. There was no relation between the
      polymorphism and hypertension (TT 11 of 100 cases, six of 45 controls).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8523391
TI  - Insulin resistance and not hyperinsulinaemia determines erythrocyte Na+/Li+
      countertransport in non-insulin-dependent diabetes mellitus.
AB  - Insulin resistance and increased erythrocyte Na+/Li+ countertransport activity
      are well documented in subjects with essential hypertension, raising the question
      whether compensatory hyperinsulinaemia might be responsible for activating
      Na+/Li+ countertransport. We measured Na+/Li+ countertransport in 63 non
      nephropathic non-insulin-dependent diabetic subjects (36 hypertensive, 27
      normotensive), finding no correlation with fasting levels of insulin (r = 0.074,
      P = 0.28), despite using a sensitive and specific insulin assay. In contrast, in
      33 of the subjects in whom insulin sensitivity was measured, Na+/Li+
      countertransport correlated significantly with the whole body glucose clearance
      rate (r = -0.37, P = 0.036). It is concluded that increased Na+/Li+
      countertransport may be a cellular marker for insulin resistance, but that
      hyperinsulinaemia is not likely to be the factor which mediates this relation.

PMID- 8523392
TI  - Ethnic origin and hypertension-associated alterations in sodium-lithium
      countertransport kinetics.
AB  - In Caucasian subjects, elevated erythrocyte sodium-lithium countertransport (SLC)
      activity, displaying an increased affinity for external Na+ (decreased KNa), has
      a strong association with hypertension and has also been proposed as a potential
      marker for vascular disease. We have compared SLC activity and the kinetic
      components, KNa and maximal rate of turnover (Vmax), of the countertransporter in
      groups of Caucasian, Asian and Black hypertensive subjects matched for ethnicity,
      age and sex with healthy normotensive controls. SLC activity was the same in all
      ethnic groups irrespective of the presence of hypertension. Similarly,
      hypertension had no impact on Vmax values within each ethnic group (normotensive
      vs. hypertensives: Caucasian, 0.360 +/- 0.186 vs. 0.335 +/- 0.137; Asian, 0.324
      +/- 0.078 vs. 0.273 +/- 0.105; black people, 0.192 +/- 0.123 vs. 0.178 +/- 0.082
      mmol Li/l erythrocytes h). However, in black people compared with the other two
      ethnic groups, Vmax was lower for both controls and hypertensives (P < 0.05;
      ANOVA). Median KNa values in hypertensive subjects were consistently lower than
      their normotensive counterparts in all ethnic groups (P < 0.01; Kruskal-Wallis);
      Caucasians, (89.1 vs. 41.2 mmol Na; P = 0.01), Asians (121.1 vs. 33.1; P = 0.04)
      and black people (74.4 vs. 27.2 mmol Na; P = 0.02; Wilcoxon). The results show
      that Vmax is altered in black people independently of the presence of
      hypertension. This contrasts with KNa which, for each ethnic group studied, is
      reduced in the hypertensive compared with the normotensive state.

PMID- 8523393
TI  - Do KCa channels and carbonic anhydrase play a role in thiazide-induced
      hyperglycaemia?
AB  - Thiazide diuretics are widely used to treat hypertension, but their use is
      associated with impaired glucose tolerance. We propose that the diabetogenic
      action of thiazides may be due to their ability to open calcium-activated
      potassium (KCa) channels in pancreatic beta-cells.

PMID- 8523394
TI  - Risk factors for ischaemic heart disease and stroke mortality in young and old
      hypertensive patients.
AB  - We investigated the predictors of cardiovascular mortality at different ages in a
      longitudinal study of 10186 hypertensive patients attending clinics in the UK.
      There were 7374 patients (51% were men) < 60 years of age and 2799 patients (44%
      men) were > or = 60 years. For IHD death the age-adjusted relative risks (RRs)
      and 95% confidence intervals (CI) for a 1 mmol/l increase in cholesterol were RR
      = 1.17 (1.07, 1.27) (men) and RR = 1.22 (1.12, 1.33) (women). The RRs for stroke
      were 0.99 (men) and 1.07 (women). In men and younger women, urea and smoking were
      important predictors of IHD and stroke death. Age differences were present in
      women for both urea and smoking. For IHD in women, smoking: RR = 2.65 (1.80,
      3.89) (< 60 years) and RR = 1.38 (1.01, 1.88) (> or = 60 years). For stroke in
      women, smoking: RR = 2.03 (1.23, 3.35) (< 60 years) and RR = 1.06 (0.70, 1.61) (>
      or = 60 years). We conclude that urea and smoking are important risk factors for
      stroke and IHD death in hypertensive women aged < 60 years, but are less
      important in those aged over 60 years. Cholesterol predicted IHD death in all men
      and women, but did not predict stroke death.

PMID- 8523395
TI  - Von Willebrand factor and endothelial damage in essential hypertension.

PMID- 8523396
TI  - Contrasting effects of nifedipine and captopril on natriuresis induced by
      isotonic saline infusion.

PMID- 8523397
TI  - Intracellular receptors and signal transducers and activators of transcription
      superfamilies: novel targets for small-molecule drug discovery.

PMID- 8523398
TI  - Substituted 2-azaspiro[5.3]nonan-1-ones as potent cholesterol absorption
      inhibitors: defining a binding conformation for SCH 48461.

PMID- 8523399
TI  - Nonsteroidal progesterone receptor ligands. 1. 3-Aryl-1-benzoyl-1,4,5,6
      tetrahydropyridazines.

PMID- 8523400
TI  - Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with
      selectivity for bone cell progesterone receptors.
AB  - A novel series of nonsteroidal heterocycles was discovered which display cell
      type selective, high-affinity (nanomolar) binding to the progesterone receptors
      from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone
      receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity
      relationships were developed for a set of these compounds, and a representative
      analog 1-(3,4-dichlorobenzoyl)-3-phenyl-1,4,5,6-tetrahydropyridazine++ + (1i, RWJ
      25333) was chosen for further evaluation. RWJ 25333 stimulated the in vitro
      proliferation of human osteoblast-like cells but not human breast cells.

PMID- 8523401
TI  - (3SR,4aRS,6SR,8aRS)-6-(1H-tetrazol-5-yl)decahydroisoquinoline-3-carboxylic acid,
      a novel, competitive, systemically active NMDA and AMPA receptor antagonist.
AB  - We report the synthesis and characterization of 6 (LY246492), which is a
      competitive N-methyl-D-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methylisoxazol
      4-yl)propanoic acid (AMPA) receptor antagonist. Tetrazole-substituted amino acid
      6 was prepared in four steps from the recently described aldehyde 7. The optical
      isomers (-)-6 and (+)-6 were obtained from the same sequence of reactions using
      the corresponding isomers of 7. The compound displaces both NMDA and AMPA
      receptor binding and antagonizes depolarizations in cortical slices evoked by
      both NMDA and AMPA. In mice and pigeons, the compound showed antagonism of
      responses mediated through NMDA and AMPA receptors. Using the resolved optical
      isomers of 6, both NMDA and AMPA antagonist activities were found to reside in a
      single isomer, (-)-6.

PMID- 8523402
TI  - Synthesis of N,N'-substituted piperazine and homopiperazine derivatives with
      polyamine-like actions at N-methyl-D-aspartate receptors.
AB  - A series of N,N'-substituted piperazine and homopiperazine derivatives have been
      synthesized with the objective of producing compounds that interact with
      polyamine modulatory sites on N-methyl-D-aspartate (NMDA) receptors. These novel
      compounds exhibited polyamine-like actions, enhancing [3H]MK-801 binding to NMDA
      receptors in rat forebrain membranes. The potencies of N,N'-bis(2
      aminoacetyl)homopiperazine (15), N,N'-bis(N-methyl-4-aminobutyl)-piperazine (7),
      and N,N'-bis(3-aminopropyl)homopiperazine (11) (EC50 18.0, 21.3, and 24.4 microM,
      respectively) to enhance [3H]MK-801 binding were comparable to that of spermine
      (EC50 5.2 microM). However, the efficacies of 15, 7, and 11 in this measure were
      lower (by approximately 40%, 32%, and 24%, respectively) than spermine, which may
      be indicative of partial agonist actions. Like spermine, the ability of these
      piperazine and homopiperazine derivatives to enhance [3H]MK-801 binding could be
      inhibited by both a competitive polyamine antagonist (arcaine) and a specific,
      noncompetitive polyamine antagonist (conantokin-G). However, unlike endogenous
      polyamines, high concentrations (up to 1 mM) of these novel polyamine-like
      compounds did not inhibit [3H]MK-801 binding. N,N'-Aminoalkylated and
      aminoacylated piperazine and homopiperazine derivatives may prove useful for
      studying polyamine recognition sites associated with NMDA receptors.

PMID- 8523403
TI  - Cyclooxygenase-2 inhibitors. Synthesis and pharmacological activities of 5
      methanesulfonamido-1-indanone derivatives.
AB  - The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX
      2), which has been proposed to play a significant role in inflammatory
      conditions, may provide an opportunity to develop anti-inflammatory drugs with
      fewer side effects than existing non-steroidal anti-inflammatory drugs (NSAIDs).
      We have now identified 6-[(2,4-difluorophenyl)-thio]-5-methanesulfonamido-1
      indanone++ + (20) (L-745,337) as a potent, selective, and orally active COX-2
      inhibitor. The structure-activity relationships in this series have been
      extensively studied. Ortho- and para-substituted 6-phenyl substitutents are
      optimal for in vitro potency. Replacement of this phenyl ring by a variety of
      heterocycles gave compounds that were less active. The methanesulfonamido group
      seems to be the optimal group at the 5-position of the indanone system. Compound
      20 has an efficacy profile that is superior or comparable to that of the
      nonselective COX inhibitor indomethacin in animal models of inflammation, pain,
      and fever and appears to be nonulcerogenic within the dosage ranges required for
      functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are
      equipotent in the in vitro assays, compound 20 is more potent in the rat paw
      edema assay, has a longer t1/2 in squirrel monkeys, and seems less ulcergenic
      than 2 in rats.

PMID- 8523404
TI  - Structure-activity relationship of omeprazole and analogues as Helicobacter
      pylori urease inhibitors.
AB  - Helicobacter pylori urease belongs to a family of highly conserved urea
      hydrolyzing enzymes. A common feature of these enzymes is the presence of two
      Lewis acid nickel ions and a reactive cysteine residue in the active site. The
      H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which
      covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase
      of gastric parietal cells. Omeprazole and eight analogues were selected based on
      their chemical, electronic, and kinetic properties, and each was incubated with
      viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which
      100 mM urea was added and the amount of ammonia formed analyzed after a further
      10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for
      the different analogues and could be expressed as a function of the pKa-value of
      the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and,
      most importantly, the rate of sulfenamide formation, in a quantitative structure
      activity relationship. The inhibition was potentiated by a lower pH (favoring the
      formation of the sulfenamide) but abolished in the presence of beta
      mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable
      of yielding the sulfenamide did not inhibit ammonia production. Treatment of
      Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4
      weeks, known to potently inhibit urease activity in vivo, as a means of
      eradicating the infection, was tested and compared with the effect of 125
      mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

PMID- 8523405
TI  - 3D-quantitative structure-activity relationships of human immunodeficiency virus
      type-1 proteinase inhibitors: comparative molecular field analysis of 2
      heterosubstituted statine derivatives-implications for the design of novel
      inhibitors.
AB  - A set of 100 novel 2-heterosubstituted statine derivatives inhibiting human
      immunodeficiency virus type-1 proteinase has been investigated by comparative
      molecular field analysis. In order to combine the structural information
      available from X-ray analyses with a predictive quantitative structure-activity
      relationship (QSAR) model, docking experiments of a prototype compound into the
      receptor were performed, and the 'active conformation' was determined. The
      structure of the receptor was taken from the published X-ray analysis of the
      proteinase with bound MVT-101, the latter compound exhibiting high structural
      similarity with the inhibitors investigated. The validity of the resulting QSARs
      was confirmed in four different ways. (1) The common parameters, namely, the
      cross-validated r2 values obtained by the leave-one-out (LOO) method (r2cv =
      0.572-0.593), and (2) the accurate prediction of a test set of 67 compounds (q2 =
      0.552-0.569) indicated a high consistency of the models. (3) Repeated analyses
      with two randomly selected cross-validation groups were performed and the cross
      validated r2 values monitored. The resulting average r2 values were of similar
      magnitudes compared to those obtained by the LOO method. (4) The coefficient
      fields were compared with the steric and electrostatic properties of the receptor
      and showed a high level of compatibility. Further analysis of the results led to
      the design of a novel class of highly active compounds containing an additional
      linkage between P1' and P3'. The predicted activities of these inhibitors were
      also in good agreement with the experimentally determined values.

PMID- 8523406
TI  - Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse
      transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship
      studies of PETT analogs.
AB  - A novel series of potent specific HIV-1 inhibitory compounds is described. The
      lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1),
      inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 microM. In MT-4
      cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 microM. The 50% cytotoxic
      dose in cell culture is > 380 microM. The chemical structure-activity
      relationship (SAR) was developed by notionally dividing the lead compound in four
      quadrants. The SAR strategy had two phases. The first phase involved optimization
      of antiviral activity through independent variation of quadrants 1-4. The second
      phase involved the preparation of hybrid structures combining the best of these
      substituents. Further SAR studies and pharmacokinetic considerations led to the
      identification of N-(2-pyridyl)-N'-(5-bromo-2-pyridyl)-thiourea (62;
      LY300046.HCl) as a candidate for clinical evaluation. LY300046.HCl inhibits HIV-1
      RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.

PMID- 8523407
TI  - Synthesis and biological evaluation of substituted flavones as gastroprotective
      agents.
AB  - Flavone (1) was found to protect against ethanol-induced gastric damage in rats;
      however, it is known that certain compounds in the flavone class, including
      flavone itself, are inducers of hepatic drug metabolizing enzymes. With the hope
      of identifying gastroprotective flavones that have minimal effects on drug
      metabolizing enzymes, we have synthesized and evaluated selected flavone analogs.
      Gastroprotective potency in the ethanol model was retained by methoxy
      substitution in the 5-position (4) and by methoxy (12) or methyl (14)
      substitution in the 7-position. A number of substituted analogs of the potent
      molecule 5-methoxyflavone (4) were also synthesized, and in many cases, these
      substitutions provided gastroprotective molecules. In order to assess liver
      enzyme induction potential, two of the gastroprotective flavones, 7
      methoxyflavone (12) and 5-methoxy-4'-fluoroflavone (26), were examined for their
      effect on liver microsomal cytochrome P450 and 7-ethoxyresorufin O-dealkylase
      (CYP1A) activity. These two compounds caused minimal changes in the cytochrome
      P450 concentration and were considerably less potent than beta-naphthoflavone as
      inducers of CYP1A enzyme activity. Furthermore, following oral administration to
      rats, 5-methoxy-4'-fluoroflavone (26) was found to protect against indomethacin
      induced gastric damage. These results indicate that, through appropriate
      substitution, flavones can be obtained that are gastroprotective but have minimal
      effects on drug-metabolizing enzymes.

PMID- 8523408
TI  - The furoxan system as a useful tool for balancing "hybrids" with mixed alpha 1
      antagonist and NO-like vasodilator activities.
AB  - The design of new vasodilator derivatives in which two different pharmacophoric
      groups are present in a single molecule has been pursued by substitution of NO
      prodrug furoxan moieties for the furanylcarbonyl function in Prazosin, a well
      known alpha 1-receptor antagonist. The aim was to obtain new antihypertensive
      agents in which two vasodilation mechanisms, alpha 1-antagonist and NO-mediated,
      can operate in an appropriate balance. The alpha 1-antagonist activity was
      assessed on rat aortic strips in the presence and in the absence of oxyhemoglobin
      (HbO2), a well-known scavenger of nitric oxide. The resulting hybrids displayed
      different pharmacological behaviors. When the 4-furoxanylcarbonyl system, bearing
      an ester or an amide function at the 3-position, was present (derivatives 7a,b),
      hybrids with predominant alpha 1-antagonist activity were obtained. By contrast,
      in the derivative 7c, in which the nitrile function is linked to the 3-position
      of the furoxan ring, the NO-mediated vasodilating properties are predominant.
      Finally, the (furoxanylsulfonyl)piperidine derivatives 13a,b showed NO
      vasodilation and alpha 1-antagonist activities in an appropriate balance. For the
      furoxan derivatives, the NO-dependent vasodilating ability, assessed on the K(+)
      depolarized aortic strip, and the NO release features under the action of thiol
      cofactors are also discussed.

PMID- 8523409
TI  - 1-Phenyl-3-(aminomethyl)pyrroles as potential antipsychotic agents. Synthesis and
      dopamine receptor binding.
AB  - A series of 1-phenyl-3-(aminomethyl)pyrroles were prepared in two steps from
      aniline and their affinities for D2, D3, and D4 dopamine receptor subtypes
      determined. A 15-fold selectivity for cloned human D4 receptors over cloned
      African Green monkey D2 receptors was observed with 1-(2-pyridyl)-4-[[3-(1
      phenylpyrrolyl)]methyl]piperazine.

PMID- 8523410
TI  - Prolyl hydroxylation regulates intracellular procollagen degradation in cultured
      rat cardiac fibroblasts.
AB  - To determine the regulatory role of prolyl hydroxylation in intracellular cardiac
      procollagen turnover, we examined the effects of prolyl 4-hydroxylase inhibitors
      (alpha, alpha-dipyridil, 3,4-dihydroxybenzoic acid ethyl ester, pyridine 2,4
      dicarboxylic acid ethyl ester) and ascorbic acid on procollagen metabolism by
      cultured, neonatal rat cardiac fibroblasts. Ascorbate-deficient fibroblasts
      showed decreased rates of prolyl hydroxylation and total collagen accumulation
      without a significant reduction in alpha 1(I) and alpha 1(III) mRNA levels. The
      fraction of newly synthesized procollagens degraded intracellularly was also
      substantially increased in ascorbate-deficient cells (50 +/- 7 v 30 +/- 3% in
      ascorbate-deficient v control fibroblasts; P < 0.05). These findings were
      associated with increased intracellular accumulation of Type I procollagen,
      enhanced secretion of "underhydroxylated" pro alpha 1 (I) polypeptide into the
      cell culture medium, and decreased extracellular Type I collagen deposition.
      Similar results were obtained by treating cells with alpha, alpha-dipyridil (300
      microns), and 3,4-dihydroxybenzoic acid ethyl ester (400 microM) in the presence
      of ascorbate. A major portion of the enhanced degradation of newly synthesized
      procollagens occurred within acidic intracellular compartments as indicated by
      the inhibition of procollagen degradation by chloroquine (25 microM). Inhibition
      of procollagen secretion by colchicine (0.5 micrograms/ml) enhanced the diversion
      to, and subsequent intracellular degradation of underhydroxylated procollagens in
      cardiac fibroblast lysosomes. We conclude that inactivation of prolyl 4
      hydroxylase increases intracellular accumulation and intralysosomal degradation
      of newly synthesized cardiac procollagen polypeptides. These observations suggest
      that procollagen prolyl hydroxylation may be important in the regulation of
      collagen accumulation by cardiac interstitial cells during fibrotic processes in
      vivo

PMID- 8523411
TI  - Altered Na(+)- H(+)- exchange activity in the spontaneously hypertensive perfused
      rat heart.
AB  - Intracellular pH (pHi) and developed pressure during hypercapnic acidosis were
      studied in the spontaneously hypertensive rat (SHR) heart and Wistar-Kyoto
      controls. Developed pressure was determined using a modified Langendorff
      isovolumic perfusion technique and 31P magnetic resonance spectroscopy was used
      to determine pHi. In response to acidosis, both developed pressure and pHi first
      decreased and then partially recovered. In the SHR group, pHi during the early
      periods of acidosis was significantly higher than in the control group while
      there was no significant difference in the steady-state pHi. The addition of 5
      (N,N)-hexamethylene-amiloride (HMA), a specific inhibitor of Na(+)-H+ exchange,
      abolished these difference. Furthermore, HMA was found to inhibit recovery in pHi
      and developed pressure during acidosis in both groups. These results demonstrate
      that Na(+)-H(+)-exchange in the rat heart plays a major role in pHi regulation
      and contributes to functional recovery during acidosis. In addition, Na(+)-H(+)
      exchange activity, as previously found in other tissues in hypertension, is
      increased in the SHR heart.

PMID- 8523412
TI  - Sodium pump inhibition in sarcolemma from ischemic hearts.
AB  - Ischemic myocardial cells lose K+ and accumulate Na+. The role of the Na+/K(+)
      pump in these changes was investigated by measuring both Na+/K(+)-ATPase activity
      and Na+ pumping in highly purified sarcolemmal vesicles from rabbit hearts made
      globally ischaemic for 1 h compared to non-ischemic controls. Purification of the
      sarcolemma was similar for control, 31 +/- 8-fold, and ischemia, 38 +/- 10-fold.
      The fraction of intact inside-out vesicles, in which Na+ pumping could be
      measured, was also the same for control, 60 +/- 16%, and ischemic, 56 +/- 8% as
      measured by 3H-ouabain binding in the presence and absence of detergent.
      Scatchard analysis of ouabain binding revealed a 26% increase in binding sites in
      ischemia compared to control. The Na+/K(+)-ATPase in the inside-out vesicles,
      measured as monensin-stimulated activity, was not affected by ischemia: 22 +/- 9
      v 21 +/- 9 mumol Pi mg -1 h -1 for control and ischemic respectively. However,
      the initial velocity of ATP-dependent Na+ pumping into inside-out vesicles,
      assayed by subsequent exchange of Na+i for 45Ca2+ by the Na(+)-Ca2+ exchanger
      present in the vesicles was inhibited in ischemia. At 18 mM Na+o the velocity for
      control vesicles was 2.4 +/- 0.2 nmol mg -1 s -1 compared to 1.1 +/- 0.1 for
      ischemia vesicles. Passive sarcolemmal Na+ permeability was unchanged after 1 h
      of ischemia. The large reduction in Na+ pumping with unchanged Na+/K(+)-ATPase
      suggests uncoupling of the Na+/K(+)-pump in ischemia and a decreased ability to
      extrude Na+ despite the increase in number of pump sites in the sarcolemma.

PMID- 8523413
TI  - Nicotine-induced exocytotic norepinephrine release in guinea-pig heart, human
      atrium and bovine adrenal chromaffin cells: modulation by single components of
      ischaemia.
AB  - The influence of single components of myocardial ischaemia, such as anoxia,
      substrate withdrawal, hyperkalemia and extracellular acidosis, on nicotine
      induced norepinephrine (NE) release was investigated in the isolated perfused
      guinea-pig heart, in incubated human atrial tissue and in cultured bovine adrenal
      chromaffin cells (BCC). In normoxia, nicotine (1-1000 mumol/l) evoked a
      concentration-dependent release of NE (determined by high pressure liquid
      chromatography and electrochemical detection) from guinea-pig heart and human
      atrium. In contrast to selective anoxia (Po2 < 5 mmHg) or glucose withdrawal,
      respectively, anoxia in combination with glucose withdrawal (5-40 min) markedly
      potentiated nicotine-induced NE release both in guinea-pig heart and human
      atrium. The sensitization of cardiac sympathetic nerve endings to nicotine was
      characterized by a lower threshold concentration and an approximate two-fold
      increase of maximum NE release, peaking after 10 min of anoxia and glucose
      withdrawal. Cyanide intoxication (1 mmol/l) combined with glucose withdrawal
      resulted in a similar increase of nicotine-induced sympathetic transmitter
      release both in guinea-pig heart and human atrium. In contrast, the nicotine
      induced (10 mumol/l) NE overflow was only slightly potentiated by 10 min of
      global ischaemia in guinea-pig heart. Both hyperkalemia ([K+] 16 mmol/l) and
      acidosis (pH 6.8-6.0) distinctly attenuated the stimulatory effect of nicotine in
      guinea-pig heart and human atrium under normoxic conditions. Consistent with an
      exocytotic release mechanism, NE release was dependent on the presence of
      extracellular calcium under all conditions tested. Furthermore, NE overflow from
      guinea-pig heart was accompanied by a release of the exocytosis marker
      neuropeptide Y (NPY; determined by radioimmunoassay). In BCC, nicotine (1-10
      mumol/l) evoked a release of NE and NPY and a transient rise of [Ca2+]i
      (determined with fura-2) during normoxia which were both dependent on the
      presence of extracellular calcium. Both hyperkalemia and acidosis markedly
      reduced the exocytotic release of sympathetic transmitters and the corresponding
      [Ca2+]i-transients. These data demonstrate that nicotine-induced cardiac
      exocytotic NE release is markedly potentiated during short-term anoxia in
      combination with glucose withdrawal. In contrast, a brief period of ischaemia
      causes only a slight sensitization of cardiac sympathetic nerve endings to
      nicotine. This discrepancy may be due to an attentuation of nicotine-evoked NE
      release by hyperkalemia and by acidosis. The protective effect of these factors
      against anoxia-induced sensitization to nicotine appears to be related to the
      inhibition of nicotine-evoked [Ca2+]i-transients.

PMID- 8523414
TI  - Further characterization of [3H]U69593 binding sites in the rat heart.
AB  - K binding sites in the crude membrane preparation of the rat heart homogenate
      were further characterized by a displacement binding assay of [3H]-U69593 with
      specific kappa ligands and a direct binding assay with [3H]-etorphine. Scatchard
      analysis of specific [3H]-U69593 binding showed that the Kd and Bmax were 6.4 +/-
      1.0 nM and 97 +/- 8 fmol/mg protein. respectively. The binding of [3H]-U69593 was
      effectively displaced by the selective kappa 1 ligands, U-69593 and U-50488H, but
      only weakly displaced by Met5-enkephalin-Arg6-Phe7, a selective kappa 2 ligand,
      which showed only 11 +/- 3% inhibition of [3H]-U69593 binding at the
      concentration of 1 microM. In addition, there was no binding site for [3H]
      etorphine, known to bind to mu, delta and kappa 2 binding sites, but not kappa 1
      binding sites. The findings suggest that the kappa binding sites in the rat heart
      most likely belong to the kappa 1 subtype. The binding sites have high and low
      affinity components as nonlinear regression analysis of the competition curves is
      best fit by two components with IC50 values of 11 +/- 2 and 62 +/- 7 nM for U
      69593, and 9.9 +/- 1.5 and 414 +/- 108 nM for U-50488H. Furthermore, the binding
      of [3H]-U69593 were inhibited by both monovalent cations (Na+, Li+) and divalent
      cations (Mg2+, Mn2+ and Ca2+).

PMID- 8523415
TI  - Intracellular [Ca2+] and Vo2 after manipulation of the free-energy of the
      Na+/Ca(2+)-exchanger in isolated rat ventricular myocytes.
AB  - We have investigated whether the Na+/Ca(2+)-exchanger has a functional regulatory
      role in the control of oxidative metabolism in suspensions of isolated rat
      ventricular myocytes. Therefore we simultaneously measured intracellular [Ca2+]
      ([Ca2+]i) with Indo-1 and respiratory rate (Vo2) after abrupt manipulation of the
      free-energy of the Na+/Ca(2+)-exchanger (delta Gexch). The average fraction of
      viable myocytes was about 90% (82% rod-shaped plus 8% viable round cells). delta
      Gexch was manipulated either by an abrupt decrease of [Na+]o (in combination with
      an increase of [K+]o or [Ca2+]o) or by changing membrane potential and/or
      intracellular cation activities with the use of gramicidin or veratridine. A
      change of extracellular cation composition caused a transient increase of [Ca2+]i
      and Vo2, with peak values after 30 to 40 s and a new steady state near control
      values after 180 to 240 s. Peak values of the transients were associated with the
      magnitude of the thermodynamic disturbance. Inhibition of sodium-pump activity
      with ouabain greatly enhanced peak values and reduced the rate of return to a new
      steady state. Reversal of the initial disturbance of delta Gexch by restoring
      [Na+]o or reduction of [Ca2+]o during the time course of the transients greatly
      accelerated return to a new steady-state. An increase of sarcolemmal sodium
      permeability with the Na-channel ligand veratridine or manipulation of [Na+]i and
      [K+]i with the Na+/K(+)-exchanger gramicidin caused monophasic increase of both
      [Ca2+]i and Vo2. The relationship between VO2 and [Ca2+]i was the same,
      irrespective of the nature of the intervention (either extracellular or
      intracellular manipulation of delta Gexch). We conclude that cytoplasmic [Ca2+]
      (thermodynamically controlled by the Na+/Ca(2+)-exchanger) is a major regulator
      of the respiratory rate in (quiescent) myocytes.

PMID- 8523416
TI  - Hypoxia preconditions rabbit myocardium via adenosine and catecholamine release.
AB  - It has been proposed that brief hypoxia can substitute for ischemia in the
      preconditioning of cardiac tissue and salvage of ischemic myocardium. To
      elucidate a possible mechanism isolated rabbit hearts were subjected to a 30-min
      period of regional ischemia by occluding a previously snared coronary artery.
      Following 2 h of reperfusion infarct size was measured by staining left
      ventricular slices with triphenyltetrazolium chloride. In control hearts
      infarction averaged 28.7 +/- 1.9% of the risk zone. If the hearts were
      preconditioned with 5 min global ischemia/10 min reperfusion prior to the
      regional ischemia, then infarction was significantly reduced to 7.2 +/- 2.0% (P <
      0.01). When global hypoxia (pO2 of perfusate 42.0 +/- 2.1 mmHg) for ten min
      substituted for the five min period of global ischemia, protection was comparable
      to that observed after ischemic preconditioning (10.2 +/- 1.5% infarction, P<
      0.01 v control). During hypoxic perfusion adenosine release increased 16-fold
      over baseline levels. This protection could not be blocked by adding levels
      either the adenosine antagonist 8-(p-sulfophenyl)theophylline or the alpha 1
      adrenergic blocker phenoxybenzamine to the hypoxic perfusate. However, co
      administration of both agents to the hypoxic perfusate successfully aborted
      protection (22.6 +/- 2.9% infarction, P N.S. v control). Therefore, 10 min of
      hypoxia releases both norepinephrine and adenosine in sufficient quantities such
      that either can completely precondition the heart.

PMID- 8523417
TI  - A novel heart derived inhibitor of vascular cell proliferation. Purification and
      biological activity.
AB  - Recently, growth factors with mitogenic properties for vascular wall cells have
      been isolated from adult heart tissue. Since angiogenesis in the heart typically
      does not occur under normal physiological conditions, despite the presence of
      many growth factors, we hypothesized the existence of growth inhibitors. To test
      this hypothesis, we subjected whole bovine heart extracts to a series of protein
      purification steps in search of such an inhibitor. The purification procedure
      consisted of ammonium sulfate precipitation followed by cation exchange
      chromatography, hydroxylapatite chromatography, ultrafiltration and
      gelfiltration. We isolated a small protein, which is an inhibitor of cell
      proliferation from the bovine heart. The inhibitor reversibly suppressed [3H]
      thymidine incorporation into nuclei of bovine aortic endothelial and smooth
      muscle cells. The moiety responsible for the inhibitory activity was identified
      biochemically (SDS Page, isoelectric focusing, HPEC) as an 11 kD protein with an
      isoelectric point of 7. The substance is a heat and acetic acid stable protein
      which does not bind to reversed phase columns because of its hydrophilic
      character. The inhibitor has no affinity to heparin sepharose. The inhibitory
      activity was destroyed by hydrolysis. No homology to any hitherto structurally
      investigated growth inhibitor was observed using the chemical determination of
      the amino acid sequence by microsequencing after previous trypsin digestion. We
      conclude that the described growth inhibitor may counteract the activity of
      mitogens that are abundantly present in normal heart. Vascular cell proliferation
      may be regulated by inhibition or production of the inhibitor.

PMID- 8523418
TI  - Temporal differences in fibroblast proliferation and phenotype expression in
      response to chronic administration of angiotensin II or aldosterone.
AB  - Chronic activation of the circulating renin-angiotensin-aldosterone system
      (RAAS), as can occur with unilateral renal ischemia (URI), is associated with an
      adverse structural remodeling of the right and left ventricles characterized by
      reparative (i.e., microscopic scars) and reactive (i.e.,
      perivascular/interstitial) fibrosis. The time course and cells involved in
      fibroplastic and fibrogenic phases of these events are unclear. Hearts were
      examined over the course of 8 weeks in rats infused with either angiotensin II or
      aldosterone, and compared to rats with URI. Tissue sections from the same heart
      were stained with hematoxylin and eosin, collagen specific picrosirius red, or
      immunolabeled with PCNA or alpha smooth muscle actin antibody. With angiotensin
      II or renal ischemia, fibroblast proliferation, presenting as focal accumulations
      at both sites of myocyte necrosis and widespread perivascular locations, was
      present in each ventricle on days 2 and 4, but not thereafter, alpha-Smooth
      muscle actin containing cells (myofibroblasts) appeared at day 2 and persisted
      through week 2 with renal ischemia and week 6 with angiotensin II. Macrophages,
      neutrophils and lymphocytes were transiently found at sites of necrosis between
      day 2-4 of renal ischemia. AngII-induced necrotic sites were characterized by
      macrophages and lymphocytes from day 2 through week 6, and neutrophils at day 2
      4. Increased collagen volume fraction, presenting as immature scars associated
      with fibroblast clusters and interstitial/perivascular fibrosis, was evident on
      day 14 in both ventricles. In contrast, fibroblast proliferation during
      aldosterone infusion did not appear in both ventricles until week 3 and was
      associated with a subsequent reparative and reactive fibrosis as early as 4
      weeks. Myofibroblasts became evident between 3-6 weeks; macrophages and
      lymphocytes were seen between 3-8 weeks. Neutrophils were not seen at any time
      point with aldosterone. Thus, the temporal cellular response and appearance of
      myocardial fibrosis associated with chronic elevations in angiotensin II and/or
      aldosterone differ. We conclude that separate pathogenic mechanisms are operative
      with these effector hormones of the RAAS.

PMID- 8523419
TI  - Effect of the antioxidant probucol on transplant arteriosclerosis in aorta
      allografted rabbits.
AB  - The attenuation of atherogenesis by oral probucol treatment, demonstrated in
      several animal studies, has been attributed to the antioxidative property of
      probucol. It is thought that probucol, by inhibiting oxidation of low density
      lipoproteins (LDL) decreases the uptake of LDL into monocytes, and thereby
      reduces the development of foam cells and fatty streaks. Also, the neointimal
      proliferation seen after balloon injury has been attenuated by treatment with
      probucol. Since foam cells and neointimal proliferation are both important
      elements of transplant arteriosclerosis, we have investigated whether probucol
      might also retard the development of experimental transplant arteriosclerosis.
      The thoracic aorta from one rabbit was transplanted as a bypass graft onto the
      abdominal aorta of another rabbit. Nine rabbits were treated with 1 g probucol
      per day and seven animals were treated with vehicle. After a recovery period of 2
      weeks, all rabbits were clamped at a human level of plasma cholesterol (6 to 7
      mmol/l) for a period of 3 weeks. The amount of dietary cholesterol necessary for
      this clamping tended to be higher in probucol treated than in vehicle-treated
      rabbits. The distribution of plasma cholesterol between lipoprotein classes was
      similar in the two groups, except for the concentration of high density
      lipoproteins (HDL), which was significantly lowered by probucol. Probucol
      markedly decreased the susceptibility of LDL and intermediate density lipoprotein
      plus very low density lipoprotein (IDL + VLDL) particles to oxidation, as
      measured by the production of conjugated dienes when adding Cu2+. Despite this,
      the development of transplant arteriosclerosis as well as the number of
      macrophages in the neointima were not significantly different in the aortic
      allografts from the two groups. These results suggest that antioxidative agents
      do not retard the development of experimental transplant arteriosclerosis.

PMID- 8523420
TI  - Left ventricular hemodynamic parameters in the course of acute experimental
      coxsackievirus B 3 myocarditis.
AB  - In susceptible DBA/2 mice coxsackievirus B 3-induced myocarditis leads to
      inflammatory and necrotic lesions in the myocardium 7-10 days after virus
      inoculation. The purpose of this study was to determine whether hemodynamic
      changes occur in murine coxsackievirus B 3 myocarditis and whether they are
      correlated to histological cardiac lesions throughout the infection. Left
      ventricular function was determined by open chest puncture of the left ventricle
      in the course of acute coxsackievirus B 3 infection. Histological cross sections
      of the heart were stained with hematoxylin/eosin and scored blindly for
      myocarditic lesions. Left ventricular function was preserved until day 7 post
      virus inoculation Left ventricular systolic pressure, +dP/dtmax and -dP/dtmax and
      heart rate declined significantly from day 7 to day 10. The decrease in these
      parameters did not correlate with viral concentrations in the heart on the day of
      hemodynamic measurements. The decrease was related to histological changes on day
      10, but not on day 7 of the infection. The data suggest (a) that a cumulative
      loss of cardiac myofibers, induced either by the virus and/or by immune reactions
      to the heart, is likely to lead to a late depression of cardiac function, and (b)
      that there is a weak and only temporary structure-function relationship in the
      heart in coxsackievirus B 3 myocarditis. Therefore, in addition to an analysis of
      histological changes, the measurement of cardiac function appears to be very
      important in order to completely evaluate the severity of myocarditis and the
      usefulness of any therapy.

PMID- 8523421
TI  - Respiratory control in heart muscle during fatty acid oxidation. Energy state or
      substrate-level regulation by Ca2+?
AB  - Fatty acids are the main fuel for the myocardium in vivo. They increase oxygen
      consumption, but the regulation of their beta-oxidation is not well known. Since
      Ca2+ and matrix volume have been implicated in the regulation of fatty acid
      oxidation in liver mitochondria, we set out to investigate the effects of Ca2+ on
      cellular respiration and energetics in the isolated perfused rat heart when
      oxidizing a short-chain fatty acid. Infusion of hexanoate increased oxygen
      consumption, while stepwise changes in the perfusate Ca2+ concentration in the
      range 0.5-2.5 mM caused the mechanical work output and oxygen consumption to
      change in parallel. Hexanoate addition increased the cellular energy state as
      determined by 31P NMR and evaluated from the cytosolic [ATP]/[ADP][Pi] ratio.
      During fatty acid infusion the energy state decreased slightly upon Ca(2+)
      induced inotropy, and after discontinuation of the hexanoate infusion the de
      energization was more pronounced. The fatty acid caused an extensive partially
      reversible reduction of flavoproteins and NAD with a slight tendency for
      oxidation during Ca(2+)-induced inotropy. The data are in agreement with the
      notion that oxygen consumption during fatty acid oxidation is mainly determined
      by the energy expenditure, even in the presence of Ca(2+)-induced alterations in
      the inotropic state. The constancy of the redox states of mitochondrial flavins
      and NADH/NAD during large changes in oxygen consumption is interpreted as
      indicating stabilization of the mitochondrial redox states by Ca(2+)-linked
      regulation.

PMID- 8523422
TI  - Effect of essential fatty acid deficiency on forskolin binding sites, adenylate
      cyclase and cyclic AMP-dependent protein kinase activity, the levels of G
      proteins and ventricular function in rat heart.
AB  - Three groups of rats were fed semi-purified diets. Diet I was deficient in
      essential fatty acids (EFAD), diet II was marginally deficient in essential fatty
      acids (MEFAD), and diet III contained adequate levels of essential fatty acids
      (control). After 9 weeks, some rats within each group were killed and cardiac
      membranes were prepared. Adenylate cyclase activity, [3H]forskolin binding sites,
      the levels of G proteins (Gi and Gs) and fatty acid composition of the membrane
      phospholipids were measured. Typical changes of EFA deficiency were observed in
      fatty acid composition of the membrane phospholipids. Adenylate cyclase activity
      was significantly lower in membranes of EFA-deficient rats than those of the
      controls. The MEFAD group gave intermediate values. Similar results were obtained
      with forskolin-stimulated activity with different concentrations of forskolin.
      Concentrations of the forskolin binding sites were also lower in the EFAD, but
      not in the MEFAD rats compared with the controls. There was no significant
      difference in forskolin binding affinities among the three groups. The decrease
      in adenylate cyclase activity in EFA-deficient rat heart was partially restored
      by feeding the control diet for 5 weeks to the EFAD or the MEFAD rats. The levels
      of Gi alpha and Gs alpha were not significantly different in cardiac membranes of
      rats fed the EFAD or the MEFAD diets from those of the control group. Lower
      adenylate cyclase activity in hearts of EFAD rats was also reflected in
      correspondingly lower activity of cAMP-dependent protein kinase. The results
      suggest an impairment of the cellular signalling pathway for the production of
      cAMP in rat heart during EFA deficiency. The beta-adrenergic response of isolated
      heart preparations obtained from rats fed the three diets was, however, not
      significantly altered.

PMID- 8523423
TI  - Effect of sulfo-N-succinimidyl palmitate on the rat heart: myocardial long-chain
      fatty acid uptake and cardiac hypertrophy.
AB  - Abnormal long-chain fatty acid metabolism has been suggested as having a role in
      the genesis of certain cardiac diseases, and depressed myocardial long-chain
      fatty acid uptake has been clinically demonstrated in some patients with
      hypertrophic cardiomyopathy. However, the site where long-chain fatty acid
      metabolism is affected in cardiomyopathy remains unclear. Although cardiac
      hypertrophy is reported to be induced in rats by a fat-free diet, little is known
      of the consequences of depressed myocardial long-chain fatty acid uptake. Sulfo-N
      succinimidyl derivatives of long-chain fatty acids have been shown to
      irreversibly inhibit long-chain fatty acid transport. To investigate the possible
      linkage of abnormal long-chain fatty acid uptake with cardiac hypertrophy,
      myocardial long-chain fatty acid uptake was blocked in rats using a sulfo-N
      succinimidyl derivative of palmitate (SSP). SSP was intraperitoneally
      administered to rats for 12 weeks, and its effects on physiological parameters,
      and cardiac morphology were studied, SSP treatment (20 mg/kg) caused a 12%
      increase in heart weight (663.7 +/- 33.6 mg in controls v 741.2 +/- 26.5 mg after
      SSP treatment) and an 11% increase in the heart weight to body weight ratio (2.46
      +/- 0.10 in controls v 2.72 +/- 0.17 after SSP) without any significant change of
      body weight. No significant differences were observed in blood pressure, heart
      rate, and serum hormones (insulin and triiodothyronine) between the control and
      SSP-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523424
TI  - Isolation of myocardial membrane long-chain fatty acid-binding protein: homology
      with a rat membrane protein implicated in the binding or transport of long-chain
      fatty acids.
AB  - Abnormal myocardial long-chain fatty acid uptake is suspected of being involved
      in certain types of heart disease, but the mechanism by which the heart takes up
      long-chain fatty acids remains unclear. The sulfo-N-succinimidyl derivatives of
      long-chain fatty acids have been reported to undergo covalent binding to a
      membrane protein and to irreversibly inhibit the transport of long-chain fatty
      acids by rat adipocytes (Harmon et al., 1991). It has been suggested that the
      membrane protein bound by these derivatives is a candidate transporter for long
      chain fatty acids in adipocytes. However, myocardial membrane long-chain fatty
      acid-binding proteins have not yet been fully investigated. Rat hearts were
      isolated and perfused with a sulfo-N-succinimidyl derivative of tritium-labeled
      palmitate ([3H]SSP). Then the [3H]SSP-binding protein was characterized by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) autoradiography and
      histological autoradiography. Myocardial palmitic acid uptake was examined after
      pretreatment of isolated perfused rat hearts with SSP. The SSP-binding protein
      was isolated from bovine hearts by successive chromatography, and the amino acid
      sequences of lysylendopeptidase-digested peptide fragments were determined. SDS
      PAGE autoradiography revealed that [3H]SSP bound to an 85-90 kDa protein derived
      from the myocardial microsomal fraction, and histological autoradiography
      demonstrated that [3H]SSP radioactivity was localized to the myocardial cell
      membrane. Pre-incubation with SSP inhibited palmitic acid uptake by isolated
      perfused rat hearts. A [3H]SSP-binding protein was also found in canine and
      bovine hearts, and was isolated from the bovine cardiac membrane fraction. Amino
      acid sequencing revealed that four peptide fragments showed strong sequence
      homology with rat adipocyte membrane protein, which is implicated in the binding
      or transport of long-chain fatty acids (Abumrad et al., 1993). We conclude that
      the SSP-binding protein is localized to the myocardial cell membrane and might be
      involved in the uptake or transport of long-chain fatty acids.

PMID- 8523425
TI  - Ischaemic preconditioning in a model of global ischaemia: infarct size
      limitation, but no reduction of stunning.
AB  - It is well known that ischaemic preconditioning delays infarct size during
      regional ischaemic insults. However, the extent of this protective effect against
      different ischaemia periods has not been established, and any reduction in
      stunning has been difficult to demonstrate with regional models. In this study we
      have investigated ischaemic preconditioning in a buffer-perfused isolated rabbit
      heart model with a global ischaemic insult, and measured both infarct volume and
      functional recovery. Experiments were performed with three ischaemia time periods
      of 15, 20 and 30 min at 37 degrees C. Infarct volume (expressed as a percentage
      of left ventricular volume) was measured by tetrazolium staining after 2 hours
      reperfusion, and left ventricular developed pressure with an intraventricular
      balloon. Hearts preconditioned with 5 min ischaemia and 10 min reperfusion were
      compared with a control group. In this model, preconditioning resulted in a 57%
      reduction in infarct volume compared with control hearts (P = 0.02) subjected to
      20 min of global ischaemia, but the degree of this infarct delaying effect was
      dependent on the ischaemia time and was only 37% (P = 0.02) and 11% (N.S.) with a
      30 min and 15 min ischaemic challenge respectively. Recovery of post-ischaemic
      left ventricular developed pressure as a percentage of the pre-ischaemic value
      correlated very well with infarct volume in control r = -0.82 (P < 0.001) and
      preconditioned r = -0.78 (P < 0.001) groups, and the slope of the regression
      lines was similar for both groups. These results demonstrate that the degree of
      protection produced by preconditioning is not uniform but varies with the length
      of the ishaemic insult. By measuring both infarct volume and functional recovery
      we have been able to confirm that any post-ischaemic improvement in global left
      ventricular function produced by preconditioning is secondary to reduced
      infarction, and hence that preconditioning does not attenuate stunning.

PMID- 8523426
TI  - Modification of gap junction conductance by divalent cations and protons in
      neonatal rat heart cells.
AB  - Myocytes were isolated from neonatal rat hearts and grown in culture dishes.
      Pairs of cells were selected to study the effect of divalent cations and protons
      on the conductance of gap junctions, gj. The experimental approach involved the
      dual voltage-clamp method and cell dialysis via patch pipette, i.e. gj was
      monitored while the cytosolic level of Ca2+, Mg2+, Sr2+, Ba2+ or H+ was modified
      in one of the cells. A dose-dependent decrease in gj developed when pCa of the
      pipette solution was lowered (range: pCa = 7.7-2.42, equivalent to a [Ca2+] of 20
      nM-3.8 mM). The gj/pCa-relationship revealed a Hill coefficient n of 0.87 and a
      half-maximal concentration pKCa of 3.5. Pretreatment with 3 mM NiCl2 and 1 micron
      ryanodine to minimize the removal of cytosolic Ca2+ did not significantly affect
      the response to gj. Similarly, gj was decreased in a dose-dependent fashion when
      pHi in the pipette solution was lowered (range: pH = 7.2-5.0, corresponding to a
      [H+] of 63 nM-10 microns). The gj/pH-relationship yielded an n of 0.92 and a pKH
      of 5.85. Pretreatment with 1 mM amiloride to minimize the extrusion of protons
      enhanced the effects of pH on gj. Simultaneous alterations in pCa and pH
      demonstrated an additive type of action of Ca2+ and H+ on gj. This is consistent
      with the existence of two types of sensors which contribute separately to the
      functional state of gj. No significant decrease in gj was detectable when the
      pipette solution contained Mg2+ or Ba2+ (up to 5 mM). Partial uncoupling was
      observed with pipette solution containing 5 mM Sr2+. We conclude that gj of
      neonatal and adult cardiomyocytes exhibit different ionic sensitivities. This
      discrepancy may reflect differences in connexin expression and/or molecular
      intermediates involved in regulating gj.

PMID- 8523427
TI  - Detection of oxidative stress in heart by estimating the dinitrophenylhydrazine
      derivative of malonaldehyde.
AB  - Accurate estimation of the oxidative stress in heart is necessary because the
      pathogenesis of many heart diseases are believed to be mediated at least in part
      from the development of oxidative stress resulting from the generation of oxygen
      free radicals and reduced antioxidant defense system. The most widely used method
      for this purpose has been the estimation of malonaldehyde (MDA), a lipid
      peroxidation product, by the thiobarbituric acid (TBA) reaction method. However,
      because of the nonspecificity of this method, the results are often erroneous.
      The present report describes a method using high-performance liquid
      chromatography (HPLC) to estimate MDA. To develop the oxidative stress, two
      different models were used: ischaemic-reperfused heart and perfusing the heart
      with a hydroxyl radical (OH+) generating system. The coronary effluents obtained
      from the isolated rat heart before ischaemia and during the reperfusion of
      ischaemic heart, as well as during the perfusion of the heart with the OH+
      generating system were collected, derivatized with 2,4-dinitrophenylhydrazine
      (DNPH) and extracted with pentane. Aliquots of 25 microliters in acetonitrile
      were injected onto a Beckman Ultrasphere C18 (3 microns) column. The products
      were eluted isocratically with a mobile phase containing acetonitrile-water
      acetic acid (40:60:0.1, v/v/v), measured at 307 nm using a Waters M-490
      multichannel UV detector and collected for gas chromatography-mass spectrometry
      (GC-MS). The peaks were identified by co-chromatography with DNPH derivatives of
      authentic standards, peak addition, and by GC-MS. The retention time for MDA-DNPH
      was 5.3 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523428
TI  - Interaction of beta-adrenoceptor and adenosine receptor agonists on
      phosphorylation. Identification of target proteins in mammalian ventricles.
AB  - The influence of the adenosine derivative (--)-N6-phenylisopropyladenosine (R
      PIA, 1 micron) and 5'N-ethylcarbox-amidoadenosine (NECA, 1 micron) on beta
      adrenergic stimulated (isoproterenol, 10 nM) phosphorylation of sarcolemmal (15
      kDa protein), sarcoplasmic reticular (phospholamban) and myofibrillar proteins
      (troponin I, C-protein) was studied in isolated 32P-labeled guinea-pig
      ventricles. The identification of the 15 kDa protein, phospholamban, troponin I
      and C-protein was based on their reaction with specific antibodies. Isoproterenol
      increased contractile parameters (developed tension, rate of tension development,
      rate of relaxation) and stimulated the phosphorylation state of a 15 kDa protein
      (now named phospholemman), of phospholamban, troponin I and C-protein (regarded
      as regulatory proteins). Isoproterenol concomitantly increased myocardial cyclic
      AMP levels. R-PIA and NECA attenuated the effects of isoproterenol on contractile
      parameters as well as on the phosphorylation of the regulatory proteins without
      affecting cyclic AMP levels. The effects of 1 microM R-PIA and 1 microM NECA on
      the isoproterenol-stimulated phosphorylation of regulatory proteins were blocked
      by the adenosine receptor antagonist 1.3-dipropyl-8-cyclopentylxanthine (DPCPX, 1
      microM). Therefore, it is concluded that adenosine derivatives acting via
      adenosine receptors can reduce the isoproterenol-stimulated phosphorylation state
      of the following regulatory proteins: phospholemman, phospholamban, troponin I
      and C-protein.

PMID- 8523429
TI  - Differential cytoprotection against heat stress or hypoxia following expression
      of specific stress protein genes in myogenic cells.
AB  - Cells respond to sub-lethal hear stress by preferential synthesis and
      accumulation of several members of functionally and compartmentally distinct
      families of heat shock (or stress) proteins (such as hsp70, hsp90, hsp60 and
      hsp27). Some of these have been implicated in the development of thermotolerance
      and resistance to other environmental stresses. The aim of this investigation was
      to determine the ability of hsp70, hsp90 or hsp60 to individually protect
      embryonal rat heart-derived H9c2 myocytes against both (i) heat stress and (ii)
      substrate-free hypoxia. When H9c2 cells were subjected to a sub-lethal stress (43
      degrees C for 30 min) they were shown to have elevated levels of hsp70, hsp90 and
      hsp60 which was maximal between 14-24 h and was associated with increased
      survival at 24 h against a subsequent lethal heat stress (47 degrees C for 2 h)
      (20.4 +/- 2.6% v 7.3 +/- 1.8%; P < 0.002). H9c2 myocytes were transfected with a
      plasmid containing human hsp70i, hsp90 beta or hsp60 expressed under the control
      of the constitutively active human beta-actin promoter or with control vector
      alone (containing no hsp gene). Stable colonies of primary transfectants selected
      for neomycin resistance showed different degrees of over-expression of hsp70i,
      hsp90 beta or hsp60 expression as determined by Western blotting using specific
      monoclonal antisera. Cells constitutively expressing high levels of hsp70i showed
      significantly higher survival against lethal heat stress compared to cells
      transfected with vector alone (39.2 +/- 6.5% v 4.5 +/- 1.0%; P < 0.0001) and also
      against 20 h of substrate-free hypoxia (86.4 +/- 3.0% v 3.5 +/- 0.7%; P <
      0.0001). Cells constitutively expressing high levels of hsp90 beta also showed
      significantly higher survival against heat stress (21.5 +/- 3.0% v 9.8 +/- 3.7%;
      P < 0.05) but were not resistant to 20 hours of substrate-free hypoxia (0.5 +/-
      1.0% v 2.0 +/- 1.7%). Cells transfected with the hsp60 plasmid showed no
      increased survival against either heat stress or substrate-free hypoxia. These
      results demonstrate that transfection of H9c2 cells with either hsp70i, hsp90
      beta or hsp60 genes confers different patterns of protection against heat stress
      and substrate-free hypoxia, indicating functional differences between stress
      proteins in their ability to protect against divergent stresses.

PMID- 8523430
TI  - Adaptation to chronic hypoxia alters cardiac metabolic response to beta
      stimulation: novel face of phosphocreatine overshoot phenomenon.
AB  - The dynamics of the changes in myocardial phosphorylated compound contents
      (inorganic phosphate: Pi; phosphocreatine: PCr; ATP) induced by 10(-6)M
      isoprenaline administration was studied, using 31P-NMR spectroscopy, in hearts
      isolated from rats adapted for three weeks to normobaric hypoxia (10% of oxygen).
      When compared with the behaviour of control hearts, the inotropic response to
      Ca2+ and isoprenaline was larger in the hearts from hypoxic rats, while the
      oxygen consumption was similar. During administration of isoprenaline, a decrease
      in the myocardial contents of high energy phosphates (ATP and PCr) and an
      accumulation of Pi was observed in both groups. After action of isoprenaline, the
      hearts from hypoxic animals showed significant overshoot of PCr, that was not
      seen in hearts from normoxic rats. The mechanisms of these alterations are
      analysed and the phosphocreatine overshoot, as well as the increased rate
      pressure product to oxygen consumption ratio, are assumed to indicate more
      efficient energy conversion in the heart from animals adapted to chronic hypoxia.

PMID- 8523431
TI  - Reciprocal changes in the postnatal expression of the sarcolemmal Na+-Ca(2+)
      exchanger and SERCA2 in rat heart.
AB  - The aim of this study was to examine the relationship between sarcolemmal Na(+)
      Ca2+ exchangers and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2)
      expression and the developmental differences in cardiac Ca2+ handling. Postnatal
      steady-state mRNA and protein levels were analysed in rat ventricular myocardium
      by Northern and immunoblot analysis, respectively. This was compared to Na+
      gradient-induced and SR oxalate-supported Ca2 transport in isolated membranes.
      Na(+)-Ca2+ exchanger mRNA declined by 75% between day 1 and 30, whereas SR Ca2+
      ATPase mRNA levels increased by 97% during this period. The Na(+)-Ca2+ exchanger
      mRNA/Ca(2+)-ATPase mRNA ratio was found to be inversely related to post-natal
      age. The changes in mRNA levels were associated with corresponding developmental
      differences in the Ca2+ transport activities of the respective membrane proteins.
      In crude membranes, the Na(+)-dependent Ca2+ transport activity (at 75 microM
      Ca2+) declined gradually (P < 0.01; mean +/- S.E.) from 17.7 +/- 2.4 nmoles
      Ca2+/g wet tissue/2s at day 1-3 (n = 5) to a value of 4.2 +/- 1.1 at day 40 (n
      =4). Conversely, SR Ca2+ uptake increased (P < 0.01) 2.6-fold during this period.
      The inversely related changes in the post-natal expression and function of the
      Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase suggest a coordinated control at the
      pretranslational level of the cellular Ca2+ transport processes mediated by the
      two membrane proteins.

PMID- 8523432
TI  - pH regulation during ischaemia-reperfusion of isolated rat hearts, and metabolic
      effects of 2,3-butanedione monoxime.
AB  - We investigated changes in pHi during ischaemia-reperfusion of isolated rat
      hearts using phosphorus nuclear magnetic resonance spectroscopy (31P NMR). Hearts
      were separated into three groups according to the perfusion buffer: bicarbonate
      buffered Krebs solution, HEPES-buffered Krebs solution, or bicarbonate-buffered
      Krebs solution plus 10(-6) M 5-(N-ethyl-N-isopropyl) amiloride (EIPA). In HEPES
      buffer and in bicarbonate buffer plus EIPA, pH at the end of 30 min of ischaemia
      and pH oscillations observed during early reperfusion were lower than in
      bicarbonate buffer. Thus, the presence of two pH regulation mechanisms (Na(+)-H+
      antiport and Na(+)-HCO3- symport) was confirmed in the isolated rat heart, while
      in HEPES buffer, pH was regulated by Na(+)-H+ antiport, and in bicarbonate buffer
      plus EIPA, by Na(+)-HCO3- symport. When cardiac contraction was inhibited by 10
      mM 2, 3-butanedione 2-monoxime (BDM), we observed, in all cases, a less
      pronounced decrease in pHi at the end of ischaemia, and in pHi oscillations at
      the onset of reperfusion. These effects were similar to those observed with 150 x
      10(-8) M verapamil and might thus be related to a decrease in intracellular
      calcium. However, with BDM, a greater reduction in the pH recovery rate was
      observed only in HEPES buffer, suggesting a possible phosphatase-like effect
      affecting the Na(+)-H+ exchange. Whatever the buffer used, the protective effect
      of BDM was reflected by an increase in the rate pressure product, which was not
      observed with verapamil.

PMID- 8523433
TI  - Contractile dysfunction caused by normothermic ischaemia and KCL arrest in the
      isolated pig heart: a 31P NMR study.
AB  - The aims of this study were to assess (1) whether contractile dysfunction caused
      by ischaemia under hyperkalaemic conditions ("cardioplegic ischaemia") is
      associated with impaired energy production or abnormalities in regulation of
      contractility and (2) whether hyperkalaemia itself contributes to contractile
      dysfunction. We used 31P and 23Na NMR spectroscopy in conjunction with
      measurements of mechanical function and oxygen consumption in Langendorff
      perfused pig hearts to evaluate the mechanism of contractile failure caused by
      (1) total global cardioplegic (17 mM [K+]) ischaemia (36 degrees C, 50 min KCl
      arrest, 45 min ischaemia, 20 min reflow with high KCl) and (2) KCl arrest alone
      (115 min) without flow cessation. KCl arrest plus ischaemia and subsequent
      reperfusion (Group I) resulted in decreases in ATP (mean +/- S.D.; 61 +/- 13% of
      initial, n = 5; P < 0.01) and pressure-rate product (PRP) (31 +/- 9%, n = 17; P =
      0.0001) while phosphocreatine (PCr), Pi, total creatine (Cr) and intracellular
      Na+ levels were unaffected. KCl arrest itself (Group II, n = 6) did not affect
      PCr, ATP or total Cr levels but decreased the PRP to 59 +/- 12% (P < 0.001).
      Oxygen consumption rates (Vo2) were reduced in both groups to similar levels (67
      +/- 18, P < 0.01 and 77 +/- 13%, P < 0.02, respectively). The efficiency of
      energy conversion to mechanical work (PRP/delta VO2) decreased to 51 +/- 15 (P <
      0.001) and 67 +/- 13% (P < 0.012) of initial levels, respectively. To assess
      metabolic and contractile reserves of post-ischaemic (n = 7) and KCl-treated (n =
      3) hearts, the effects of isoproterenol (Iso) and increased Ca2+ were compared
      with those in normal beating hearts (Group III, n = 3). In all groups treatment
      with Iso (0.1 micron) greatly increased PRP (to 526 +/- 116, 203 +/- 16 and 198
      +/- 8% of the level prior to stimulation (baseline), P < 0.01, respectively) and
      Vo2 (162 +/- 9, 153 +/-16 and 128 +/-10% of baseline, P < 0.05, Respectively).
      Increasing [Ca2+] from 1 to 1.66 mM produced less stimulation than Iso: PRP
      increased to 195 +/- 23, 156 +/- 13 and 163 +/- 22% (P < 0.05) and Vo2 increased
      to 138 +/- 22 (P < 0.05), 115 +/- 4 and 120 +/- 10% of baseline in Groups I, II
      and III, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8523434
TI  - Influence of thyroid status on postnatal maturation of calcium channels, beta
      adrenoceptors and cation transport ATPases in rat ventricular tissue.
AB  - In order to examine the influence of thyroid hormones on the postnatal
      development of cardiac excitation-contraction coupling, newborn rats were made
      hypo- or hyperthyroid, and several key factors involved, directly or indirectly,
      in Ca2+ signaling: L-type Ca2+ channels (1,4-dihydropyridine receptors), Ca(2+)
      release channels of sarcoplasmic reticulum (ryanodine receptors), beta
      adrenoceptors, thapsigargin-sensitive Ca(2+)-ATPase and Na(+)-K(+)-ATPase (enzyme
      activity and ouabain receptors), were investigated in membrane fractions from
      ventricular tissue, collected on day 21. Hypothyroidism induced a moderately
      lower myocardial density of 1,4-dihydropyridine and ryanodinerece receptors
      (reduced by 23% and 31%, respectively, with respect to euthyroid controls), and
      much reduced levels of beta-adrenoceptors, Ca(2+)-ATPase and Na(+)-K(+)-ATPase
      activities. Hyperthyroidism induced only a moderate (22%) decrease in the
      myocardial density of 1,4-dihydropyridine receptors and a marked (240%) increase
      of the alpha 2 isoform of Na(+)-K(+)-ATPase. To analyse the subsarcolemmal
      localization of L-type channels, microsomal fractions were subfractionated by
      density equilibration in sucrose gradient. In gradients from control and
      hyperthyroid rats, most 1,4-dihydropyridine receptors were recovered in high
      density subfractions, their distribution following that of ryanodine receptors,
      whereas, in gradients from hypothyroid rats, most 1,4-dihydropyridine receptors
      were recovered in low-density subfractions, together with beta-adrenoceptors and
      Na(+)-K(+)-ATPase. We conclude that thyroid hormones are important for the
      postnatal changes in the myocardial density of several channels and pumps
      involved in Ca2+ fluxes, as well as for the postnatal redistribution of L-type
      Ca2+ channels from non-junctional sarcolemma to junctional structures, a key
      process for the efficient operation of excitation-contraction coupling in adult
      ventricular tissue.

PMID- 8523435
TI  - Influence of dietary polyunsaturated fatty acids on contractility, lusitropy and
      compliance of isolated rat myocardium.
AB  - Two groups of 15 rats were fed for 4 weeks with diets containing 15% by weight of
      fat varying in polyunsaturated fatty acids (PUFA) content and type. Diet C18:2 (n
      6) contained 20% of total fatty acids as linoleic acid and small amount of (n-3)
      PUFA (0.4% of the total fatty acids). Diet LC (n-3) contained the same amount of
      18:2 (n-6) and of long chain (n-3) C20 and C22 PUFA (10% of the total fatty
      acids). Contents of both saturated fatty acids and amount of total PUFA were kept
      constant in the two diets. Left ventricular papillary muscle mechanics were
      studied blind at Lmax and over the entire load-continuum, in terms of inotropy,
      characteristics of the force-velocity relationship, relaxation and compliance.
      Inotropy, force-velocity relationships and muscle compliance were similar in both
      groups. There was a trend towards a lower peak lengthening velocity at preload in
      the LC (n-3) group (P = 0.10) together with an unchanged peak rate of isometric
      force decline. This resulted in a significant impairment of the two mechanical
      indexes testing the load dependence of myocardial relaxation (P = 0.019 and P =
      0.002). In conclusion, short-term differences in PUFA regimen were associated
      with an unchanged myocardial contractility and economy of force generation. The
      decreased load dependence of relaxation together with unchanged myocardial
      compliance strongly favored a physiological relevance of the previously reported
      modifications of sarcoplasmic reticulum phospholipid composition and calcium
      transport under (n-3) PUFA regimen.

PMID- 8523436
TI  - Localization of muscarinic receptors in human heart biopsies using rabbit anti
      peptide antibodies.
AB  - Immunocytochemistry of muscarinic receptors on human heart biopsies from patients
      with heart disease was studied using rabbit antibodies against a synthetic
      peptide corresponding to amino acids 168-192 of the second extracellular loop of
      the human M2 muscarinic receptor. By using both light and electron microscopic
      immunocytochemistry techniques, muscarinic receptors were visualized on
      sarcolemma of human myocytes from patients with different heart diseases such as
      coronary heart disease and dilated cardiomyopathy in adults and congenital heart
      disease in children. The patchy distribution of immunoreactivity suggests a
      muscarinergic activity in vivo. These reactivities were abolished by
      preincubation of antibodies with antigenic peptide and were not shown in the
      absence of antibodies. Moreover, these antibodies were able to interfere with
      muscarinic ligand binding in myocardium from human dilated cardiomyopathy as
      shown by decreases in binding sites and antagonist affinity. These results
      demonstrate that the antibodies against the second extracellular loop of the
      human M2 muscarinic receptor can specifically recognize muscarinic receptors in
      human tissue and display pharmacological activity in human diseased myocardium,
      confirming their usefulness for the study of localization and function of
      muscarinergic activity in the human heart.

PMID- 8523437
TI  - Potassium channels and preconditioning of isolated rabbit cardiomyocytes: effects
      of glyburide and pinacidil.
AB  - Calcium tolerant rabbit cardiomyocytes, isolated by collagenase perfusion, were
      preincubated for varying periods of time followed by resuspension in fresh media
      and centrifugation into an ischaemic pellet with restricted extracellular fluid.
      Pellets were incubated for 240 min under oil at 37 degrees C to mimic severe
      ischaemia. Time to onset of ischaemic contracture (rod to square transformation)
      and trypan blue permeability following resuspension in 85 mOSM media were
      monitored at sequential times. The protocol of Series 1 was a 5-10 min pre
      incubation, immediately followed by ischaemic pelleting. Preincubation with
      pinacidil (50 microM) protected cells from ischaemic insult, but pinacidil added
      only into the ischaemic pellet did not protect. Protection was abolished by the
      protein kinase (PKC) inhibitors chelerythrine (10 microM) added with pinacidil
      and calphostin C (200nM) added only into the ischaemic pellet. Neither PKC
      inhibitor had an effect on injury of untreated ischaemic myocytes (data not
      shown). Series 2-5 were preconditioning protocols with a 10 min intervention
      period, followed by a 30 min oxygenated drug-free period, prior to ischaemic
      pelleting. In series 2 pinacidil protected cells from ischaemic insult and this
      protection was abolished when glyburide (10 microM) was present during
      preincubation, or during post-incubation and ischaemia. Glyburide only partially
      inhibited the protection when glyburide was added only into the ischaemic pellet.
      In Series 3, 8-sulfophenyltheophyline (SPT)(100 microM) or adenosine deaminase
      during preincubation, or SPT only added into the ischaemic pellet abolished
      pinacidil's protection. In Series 4, cardiomyocytes were ischaemically
      preconditioned by pelleting for 10 min followed by 30 min reoxygenation.
      Glyburide during initial ischaemic blocked protection, but when added during post
      incubation and into the final pellet protection was not reduced. In Series 5 8
      cyclopentyl-1,3,dipropylxanthine (DPCPX) (10 microM) added into the final pellet
      abolished protection by pinacidil, but not protection following ischaemic
      preconditioning. In contrast to pinacidil, ischaemically preconditioned cells
      maintain protection in the presence of glyburide, indicating that: (1) pinacidil
      does not exactly mimic preconditioning and (2) ischaemically preconditioned cells
      do not require opened K+ATP channels for protection, although they appear to be
      important during initiation of the preconditioned state. It is hypothesized that
      pinacidil opening of K+ channels may facilitate induction of preconditioning.

PMID- 8523438
TI  - Properties of cardiac cells from dystrophic mouse.

PMID- 8523439
TI  - Acidosis masks beta-adrenergic control of cardiac L-type calcium current.
AB  - The beta-adrenergic control of the L-type Ca2+ current (ICa) was examined as a
      function of extracellular pH (pHo) in guinea-pig ventricular myocytes using the
      whole-cell voltage-clamp technique. ICa was elicited in Cs(+)-loaded myocytes by
      depolarizing pulses from a holding potential of -40 mV. The maximum ICa density
      in response to 0.01 or 1 microM isoproterenol was significantly less in myocytes
      pretreated with acidic external solution (pHo 6.6 or 5.8) compared with cells
      studied at control pHo 7.4. This acidosis-induced decrease in beta-responsiveness
      was also accompanied by a similar reduction in basal current density. Myocytes
      studied under alkaline conditions (pHo 8.2) also had reduced beta-responsiveness
      although basal ICa density tended to be greater than control. In addition to the
      diminished effects of isoproterenol, acidic myocytes had smaller responses to
      extracellular forskolin and internally applied adenosine 3',5'-cyclic
      monophosphate, compared with control. The blunted responses to these latter
      stimuli were similar in magnitude to that observed with 1 microM isoproterenol.
      These findings suggest that protons interfere with the beta-adrenergic control of
      ICa primarily by a direct inhibition of the Ca2+ channel which independently
      masks the effects of the adenylyl cyclase cascade.

PMID- 8523440
TI  - Type V, but not type VI, adenylyl cyclase mRNA accumulates in the rat heart
      during ontogenic development. Correlation with increased global adenylyl cyclase
      activity.
AB  - Type V and VI adenylyl cyclase mRNAs are the two main cyclase isoforms expressed
      in the mammalian heart. A recent report has shown that their expression is
      differentially regulated during ontogenic development, but the accumulation of
      the two mRNA species and their concentration ratio have not been determined. We
      thus determined the accumulation and the relative amounts of type V and VI
      adenylyl cyclase mRNA in fetal, neonatal and adult rat hearts, using a sensitive
      ribonuclease protection assay. In 18-day-old fetuses, the two adenylyl cyclase
      mRNA isoforms were weakly expressed in approximately equal amounts (type V
      mRNA/type VI mRNA = 0.93 +/- 0.09). Further development was characterized by a
      sharp increase in type V adenylyl cyclase mRNA (x 1.9 in neonates v fetuses, P <
      0.01; x 2.4 and x 4.5 in adults v neonates and fetuses, respectively, P < 0.01
      for both comparisons) and a slight, non-significant fall in type VI mRNA (P =
      0.16). As a result, the type V mRNA/type VI mRNA ratio was 2.86 +/- 0.57 and 9.09
      +/- 1.21 in neonatal hearts and adult ventricles, respectively (P < 0.01 v ratio
      in fetal hearts for both comparisons; P < 0.01 for ratio in adult ventricles v
      ratio in neonatal hearts), and the overall amount of the two mRNA isoforms was
      2.3 times greater in adult than in fetal hearts (P < 0.01). This increase was
      paralleled by an increase in basal and isoproterenol- and forskolin-stimulated
      adenylyl cyclase activities in adult hearts compared to fetal and neonatal hearts
      (P < 0.01 for the three comparisons). Our results demonstrate that type V
      adenylyl cyclase mRNA accumulates in the rat heart after birth to become the
      highly predominant isoform in the adult heart. They further suggest that the
      increase in cardiac adenylyl cyclase activity observed during rat development is
      due to this accumulation.

PMID- 8523441
TI  - Novel pathways involved in recovery of guanine nucleotides in reperfused
      ischaemic rat hearts and reoxygenated myocytes.
AB  - During global ischaemia for various lengths of time followed by reperfusion, the
      adenine and guanine nucleotide concentrations altered in parallel. Measurements
      of purine precursors and breakdown products suggested that GTP was resynthesised
      from inosine, adenosine or the adenine nucleotides in reversible ischaemia:
      however, the use of three different inhibitors of the key enzyme in this pathway.
      IMP-dehydrogenase, was entirely without effect. To eliminate the endothelial cell
      barrier, the experiments were repeated with anoxic/reoxygenated cardiac myocytes.
      The lower rate of recovery of purine nucleotide triphosphates in myocytes
      compared with perfused hearts would tend to confirm the important role suggested
      for endothelial cells in nucleoside salvage. GTP resynthesis took place after
      reoxygenation by some unknown pathway unaffected by the presence of large
      concentrations of an IMP-dehydrogenase inhibitor. The possible relationship of
      these findings to purinogen, the recently discovered major source of adenine
      nucleotides in heart, is discussed.

PMID- 8523442
TI  - KATP-channel openers protect against increased cytosolic calcium during ischaemia
      and reperfusion.
AB  - There is ample evidence that potassium channel openers protect the ischaemic
      myocardium. Although the protective mechanism is unknown, indirect evidence
      suggests that potassium channel openers reduce calcium influx during ischaemia
      which may explain their protective effects. However, recently discovered
      potassium channel openers such as BMS-180448 are cardioprotective without
      displaying classical indications of calcium lowering. The current study was
      designed to provide direct evidence that potassium channel openers delay or
      prevent increased intracellular free calcium in the myocardium during ischaemia
      and reperfusion. Cytosolic calcium concentrations were directly measured in
      perfused rat hearts during global ischaemia by 19F-NMR of the calcium chelator 5F
      BAPTA. The cytosolic Ca2+ concentration in vehicle-treated hearts increased from
      a pre-ischaemia average of 310 +/- 40 nM to 1000 +/- 130 nM during 25 min of
      ischaemia, followed by partial recovery to 530 +/- 100 nM during 19 min of
      reperfusion. In contrast, the cytosolic Ca2+ concentration in hearts treated with
      potassium channel openers BMS-180448 and cromakalim remained low throughout
      ischaemia, changing from pre-ischaemia averages of 270 +/- 30 nM to 230 +/- 60 nM
      and from 240 +/- 20 nM to 170 +/- 30 nM during 25 min of ischaemia, respectively.
      The cytosolic Ca2+ concentrations in these hearts increased to 440 +/- 110 nM in
      BMS-180448 treated hearts and 290 +/- 60 nM in cromakalim treated hearts during
      the first 6 min of reperfusion, and were 460 +/- 60 nM for BMS-180448 and 600 +/-
      70 nM for after cromakalim 19 min of reperfusion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523443
TI  - Alterations in sarcoplasmic reticulum calcium uptake, relaxation parameters and
      their responses to beta-adrenergic agonists in the developing rabbit heart.
AB  - Developmental changes in cardiac sarcoplasmic reticulum function, which may
      reflect alterations in the myocardial rate of relaxation and its responses to
      beta-adrenergic stimulation, were assessed using fetal, 4-day-old, 21-day-old and
      adult rabbit hearts. The fetal hearts exhibited the slowest rate of relaxation (
      dP/dt) and the lowest Vmax and EC50 of the sarcoplasmic reticulum Ca(2+)-pump for
      Ca2+ compared to the other age groups. These parameters were similar among the 4
      day-old, 21-day-old and adult hearts. The low physiological and biochemical
      parameters in the fetal hearts reflected reduced levels of expression of the
      sarcoplasmic reticulum Ca(2+)-pump and its inhibitor, phospholamban, assessed by
      quantitative immunoblotting. Isoproterenol perfusion of fetal hearts had no
      significant effect on their relaxation parameters or on the EC50 of the Ca(2+)
      pump for Ca2+, consistent with the low relative levels of phospholamban expressed
      in these hearts. However, perfusion of the 4-day-old, 21-day-old and adult hearts
      with isoproterenol resulted in significant increases in the rates of relaxation
      of each group. The increases in relaxation parameters were associated with
      decreases in the EC50 of the cardiac sarcoplasmic reticulum Ca(2+)-pump for Ca2+,
      suggesting a phosphorylation-mediated relief of the phospholamban inhibitory
      effects. These findings indicate that developmental regulation of the levels of
      the activity of the cardiac sarcoplasmic reticulum Ca(2+)-pump may reflect
      alterations in cardiac relaxation parameters and their modulation by beta
      adrenergic agonists.

PMID- 8523444
TI  - Modulation of cardiac M2 muscarinic receptor binding by progesterone-related
      steroids.
AB  - We have previously shown that progesterone, but not estradiol or testosterone,
      can compete with [3H]N-methyl scopolamine (NMS) for the cardiac M2 muscarinic
      binding site. Experiments have been carried out to investigate the inhibitory
      effects of a large variety of progesterone-like steroids on the M2 muscarinic
      receptor. These studies were performed with the aid of a new binding assay which
      uses intact tissue in the form of ventricular micropunches. Our data show that
      synthetic, clinically-used progestins such as Provera, norgesterel and
      cyproterone are largely ineffective at the M2 binding site whereas the naturally
      occurring progesterone derivatives 17 alpha hydroxy progesterone and Reichstein's
      Substance S are highly active. (Ki values 5 x 10(-6)M and 1 x 10(-6)M,
      respectively). Minor structural modifications such as acetylation of the 17 alpha
      hydroxy group abolishes activity. Steroids known to exert cell membrane effects,
      such as alfaxalone and pregnenolone sulfate, had no influence on [3H] NMS
      binding. The progesterone antagonist RU-486 did not block the inhibitory effect
      of progesterone. Moreover, this putative receptor may be located in the
      cardiomyocyte membrane since 17 alpha hydroxy progesterone induces rapid
      dissociation of [3H] NMS from its binding site (30% reduction in 5 min). We
      attempted to further localize the inhibitory locus to the M2 receptor itself by
      means of the irreversible antagonist propylbenzilylcholine mustard (PrBCM).
      Ninety percent of the M2 receptor could be blocked by PrBCM (10(-6) M), an effect
      reversible by the specific muscarinic antagonist scopolamine methyl bromide but
      not by progesterone. These results suggested that progesterone does not interact
      directly with the [3H] NMS labelled M2 binding site.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523445
TI  - Nisoldipine improves ventricular function in rats with ischemic heart failure.
AB  - To determine whether calcium channel blockade is effective in the prevention of
      the cascade of events leading to the thin walled, decompensated ventricle
      observed in ischemic heart failure, inhibition of transsarcolemmal transport of
      calcium by nisoldipine was examined in rats in which luminal narrowing of the
      left main coronary artery was utilized to produce global cardiac ischemia.
      Coronary artery narrowing was produced in rats at 2 months of age and animals
      were maintained on nisoldipine (10 mg/kg body weight) (CANN) or water (CANW)
      until time of sacrifice 1 month later. Surgical intervention resulted in a 50%
      reduction in coronary artery luminal diameter in both experimental groups and was
      associated with an increase in kidney and lung weights in only CANW animals.
      Heart weights were also increased in the water treated coronary artery narrowed
      group. In CANW rats, systemic arterial and left ventricular systolic pressures
      were reduced whereas left ventricular diastolic pressures were elevated. Peak
      rates of pressure rise and decay and cardiac output were also reduced in CANW
      rats. Treatment with nisoldipine prevented the detrimental impact of ischemic
      heart disease to an extent that all measured parameters in CANN rats were found
      to be intermediate between unoperated controls and CANW animals. Thus, calcium
      channel blockade was therapeutic in the prevention of cardiac dysfunction and
      failure seen after the onset of ischemic heart disease in rats. Furthermore, the
      detrimental impact of ischemic heart disease was ameliorated by early and
      continuous treatment with the calcium channel blocker, nisoldipine.

PMID- 8523446
TI  - Tetradecylthioacetic acid reduces the amount of lipid droplets, induces
      megamitochondria formation and increases the fatty acid oxidation in rat heart.
AB  - The effects of prolonged administration (3 months) of a 3-thia fatty acid
      analogue and omega-3-fatty acids on cardiac fatty acid oxidation and the volume
      fraction of lipid droplets and mitochondria in cardiomyocytes were investigated.
      Doses were 1 g/day/kg body weight, except 150 mg/day/kg body weight for
      tetradecylthioacetic acid (a 3-thia fatty acid). One group served as control and
      did not receive any treatment. The volume fraction of lipid droplets in
      cardiomyocytes was significantly lower in the tetradecylthioacetic acid group
      compared to the other groups. Mitochondrial beta-oxidation was 60% greater and
      fatty acyl-CoA oxidase activity was increased by 430% in the tetradecylthioacetic
      acid group compared to control. This was accompanied by a greater volume fraction
      of mitochondria in cardiomyocytes (0.514 +/- 0.032% in tetradecylthioacetic acid
      v 0.318 +/- 0.007% in control) which was due to an increased size of
      mitochondria. The volume fraction of mitochondria was also greater in
      eicosapentaenoic acid (EPA) treated rats compared to control, but the enzymic
      activities were unaffected. Docosahexaenoic acid (DHA) treatment resulted in a
      greater volume fraction of lipid droplets in the cardiomyocytes, but the volume
      fraction of mitochondria and enzyme activities were unaltered. These results
      indicate that EPA and DHA have different effects on the modulation of
      mitochondrial biogenesis. Tetradecylthioacetic acid treatment results in
      megamitochondria formation and increased peroxisomal and mitochondrial beta
      oxidation with a concomitant reduction of lipid droplets in the cardiomyocytes.

PMID- 8523447
TI  - Cardiac troponin C as a target protein for a novel calcium sensitizing drug,
      levosimendan.
AB  - The role of cardiac troponin C (cTnC) as a target protein for the calcium
      sensitization by levosimendan, pimobendan, MCI-154 and EMD 53998 was evaluated
      using purified recombinant human cTnC. For determination of calcium- and
      magnesium-dependent binding of the compounds to cTnC a new type of cTnC-HPLAC
      column was used. Furthermore, dansylated cTnC was utilized to study the effect of
      the calcium sensitizing compounds on calcium-induced conformation of cTnC. Only
      levosimendan showed calcium-dependent and to a lesser extent magnesium-dependent
      retention in the cTnC column. The findings indicate that levosimendan binds both
      to the N-terminal and C-terminal domains of cTnC. In agreement with this, only
      levosimendan shifted the calcium-induced fluorescence curve of dansylated cTnC to
      the left. In the control experiments Ca50 and KCa2+ were calculated to be 2.73
      microM and 4 x 10(5) M-1, respectively. Levosimendan at 3 microM decreased the
      value of Ca50 to 1.19 microM. In conclusion, it is suggested that the mechanism
      of calcium sensitizing effect of levosimendan, unlike that of the other calcium
      sensitizers, is based on calcium-dependent binding to the N-terminal domain of
      cTnC. This is proposed to amplify the trigger of contraction induced by cTnC in
      the cardiac muscle.

PMID- 8523448
TI  - Activation of ATP-dependent K+ channels enhances myocardial protection due to
      cold high potassium cardioplegia: a force-frequency relationship study.
AB  - The hypothesis that nicorandil might enhance myocardial protection due to cold St
      Thomas' Hospital (STH) solution ([K+]o 16 mmol/l) through opening of cardiac KATP
      channels was assessed in isometrically contracting guinea-pig papillary muscles
      submitted to 120 min of cardioplegic hypoxia followed by 60 min of normothermic
      reoxygenation. Right ventricular papillary muscles were paced (2 ms, 4 mA) in an
      organ bath and superfused with oxygenated (O2 content 16 ml/l) Tyrode's solution
      (37 degrees C). The force-frequency relationship in the range 1600-300 ms cycle
      length (CL) was studied. Preparations were randomized to receive 120 min cold (20
      degrees C), non-oxygenated (O2 content 5 ml/l) STH solution while continuously
      stimulated at 1600 ms CL, with: (1) saline (No-additive, n = 12); (2) DMSO 1%
      (Vehicle, n = 8); (3) nicorandil 1 mmol/l (n = 8); (4) nicorandil 1 mmol/l plus
      glibenclamide 1 mumol/l, the latter also given, before STH solution, in Tyrode's
      solution for 15 min (n = 8); (5) glibenclamide 1 mumol/l, also circulated, before
      STH solution, in Tyrode's solution for 15 min (n = 8); (6) nitroglycerin 100
      mumol/l (n = 4); in addition, we studied: (7) STH solution with no-additive and
      no-pacing (n = 4); (8) cold Tyrode's in place of cold STH solution (n = 4).
      Inotropic state was investigated by measuring: (i) velocity of developed tension
      (DT), obtained by dividing DT by time to peak tension; (ii) percentage (from
      precardioplegia values) velocity changes of DT; (iii) log velocity of DT. Post
      cardioplegic recovery of contractility (including force-frequency relationship)
      was assessed in all preparations: (a) 60 min after reoxygenation with Tyrode's
      solution; (b) after further 15 min superfusion with the positive inotropic agent
      dobutamine (10 mumol/l). In parallel experiments, action potential duration (APD)
      50% changes induced by nicorandil or glibenclamide plus nicorandil in
      spontaneously beating atrial (n = 4) or electrically driven (1600 ms CL)
      ventricular (n = 8) tissues during 10 min of STH solution were investigated.
      Based on force-frequency relationship, at 60 min reoxygenation, in absence of
      cardioplegia, the lowest recovery of myocardial contractility was seen
      (stunning). In STH solution, there was moderate to severe stunning, which was
      unaffected by removing pacing during cardioplegia, or by vehicle or
      nitroglycerin. In contrast, nicorandil improved recovery of contractility (F =
      3.01, P = 0.0106). After dobutamine, nicorandil preparations showed the highest
      positive inotropic response, which was completely offset by glibenclamide (F =
      3.47, P = 0.0046).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8523449
TI  - Transient inhibition of glucose uptake mimics ischemic preconditioning by
      salvaging ischemic myocardium in the rabbit heart.
AB  - The aim of this study was to test whether transient inhibition of glucose uptake
      could precondition the rabbit heart. Rabbit hearts experienced 30 min regional
      ischemia followed by either 120 min (isolated heart protocol) or 180 min (in situ
      protocol) reperfusion. Infarct size was determined by tetrazolium staining. In
      isolated heart experiments, 15 min perfusion with glucose-free Krebs buffer
      starting 30 min prior to ischemia significantly limited infarct size to 9.9 +/-
      2.6% of the risk zone as compared with 29.4 +/- 1.7% infarction in controls. This
      protection could be blocked (30.8 +/- 3.4%) by polymyxin B (50 microM), a protein
      kinase C inhibitor, but not by 8-(p-sulfophenyl)theophylline, an adenosine
      receptor inhibitor, suggesting the mechanism was similar to that of ischemic
      preconditioning but without involvement of adenosine receptors. Pyruvate and
      acetate inhibit glucose uptake without incurring a metabolic deficit. When 20 mM
      pyruvate or 1 mM acetate was added to the glucose-containing buffer for 15 min
      prior to ischemia, protection was evident (12.0 +/- 3.0% and 10.0 +/- 3.7%
      infarction, respectively). However, when acetate (1 mM) was present in the
      perfusate throughout the experiment, neither omission of glucose nor addition of
      pyruvate caused protection (26.1 +/- 2.2% and 28.9 +/- 4.7% infarction,
      respectively). Furthermore, when in situ hearts which preferably utilize lipid
      substrates were treated with pyruvate (2 g/kg i.v. 20 min before ischemia),
      infarct size was 40.3 +/- 3.0%, which did not differ from that in untreated
      hearts (38.6 +/- 3.2%). Hence transient inhibition of glucose uptake can
      precondition the heart, but only if other substrates which are utilized in
      preference to glucose are absent.

PMID- 8523450
TI  - Dose/response curves of lipoic acid R-and S-forms in the working rat heart during
      reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow.
AB  - Micromolar concentrations of lipoic acid racemate added to a working rat heart
      during hypoxia have been previously found to improve aortic flow during
      subsequent reoxygenation. Since the R-form represents the naturally occurring
      form of lipoic acid, and the S-form does not reveal a positive influence on ATP
      synthesis in isolated mitoplasts, a dose/response curve of both enantiomers has
      been performed in working rat hearts. After the end of perfusion mitochondria
      were isolated and further analysed. At a concentration of 0.05-0.1 mumol of the R
      enantiomer, aortic flow rises precipitously during reoxygenation, reaching over
      70% of normoxic values compared to 50% of the controls. By contrast, with the S
      enantiomer a value of about 60% is attained at 1 mumol, only. Accordingly, ATPase
      activity in mitochondria isolated from rat hearts previously treated with 0.05
      0.1 mumol of the R- or S-enantiomer was significantly decreased or increased
      respectively. Consequently, whereas mitochondrial ATP synthesis was increased
      when the R-enantiomer was previously added to the working heart at 0.05-0.1 mumol
      concentration, with the S-enantiomer ATP synthesis remained within the control
      range. Mitochondrial membrane fluidity, measured with diphenylhexatriene,
      revealed a trend towards increase with the R- and decrease with the S-enantiomer.
      The total amount of thiol added at 0.1 mumol concentration is consistent with a
      value of 2 nmol/mg mitochondrial protein. This value has previously been found to
      be connected with -SH groups which add oligomycin-sensitivity to the ATPase
      complex. It is suggested that oligomycin-sensitive mitochondrial -SH groups
      contribute to the overall efficiency of low concentrations of lipoic acid R
      enantiomer to enhance aortic flow.

PMID- 8523451
TI  - Inhibition by angiotensin II type 1 receptor antagonist of cardiac phenotypic
      modulation after myocardial infarction.
AB  - The purpose of this study was to examine the cardiac phenotype and remodeling
      after myocardial infarction and the effect of the angiotensin II type 1 (AT1)
      receptor antagonist (TCV-116) on the gene expression. Myocardial infarction in
      rats was produced by ligation of the coronary artery. TCV-116 (10 mg/kg/day) was
      administered orally to rats from 1 day after myocardial infarction. At 1, 2 and 3
      weeks after myocardial infarction, blood pressure and heart rate were measured,
      and the heart was removed. The left ventricle was measured for infarct size and
      weight, and then the total RNA from the non-ischemic left ventricle was
      extracted. mRNAs in the non-ischemic left ventricle were measured by Northern
      blot analysis. The weight of the non-ischemic left ventricle was significantly
      increased 3 weeks after infarction. This was completely prevented by TCV-116
      treatment. mRNA levels for beta-myosin heavy chain (beta-MHC), atrial natriuretic
      polypeptide (ANP), collagen types I and III and transforming growth factor-beta 1
      (TGF-beta 1) in the non-ischemic left ventricle were increased by a factor of
      3.0, 6.7, 7.9, 4.0 and 1.4 (P < 0.01), respectively, 1 week after infarction.
      There was no increase in alpha-skeletal actin mRNA at 1 and 2 weeks, but it was
      increased by a factor of 2.9 (P < 0.05) at 3 weeks. On the other hand, there was
      no change in alpha-MHC mRNA during the 3 weeks. TCV-116 significantly suppressed
      the increased gene expression of beta-MHC and alpha-skeletal actin in the non
      ischemic myocardium at all time points, and also suppressed the expression of ANP
      at 2 and 3 weeks. However, TCV-116 failed to inhibit the expression of collagen I
      and III mRNAs at 1 and 3 weeks. These results show that myocardial infarction
      causes a rapid shift of myocytes to fetal phenotype and a rapid activation of
      collagen genes in the non-ischemic myocardium. AT1 receptor may be responsible
      for the phenotypic modulation of myocytes following myocardial infarction.

PMID- 8523452
TI  - Vascular and contractile function and tissue metabolites after prolonged
      hypothermic ischaemia and reperfusion: comparison of single- versus multi-dose
      infusions with two cardioplegic solutions in blood-perfused neonatal pig hearts.
AB  - The effects of single- and multi-dose cardioplegia on post-ischaemic vascular
      function and contractile activity were compared in 69 blood-perfused neonatal pig
      hearts, as were the protective properties of two different cardioplegic
      solutions. Hearts (n = 6 or 9 per group) from neonatal (3-5 days old) pigs were
      excised, arrested with a 2 min infusion (at 15 degrees C) of St Thomas' Hospital
      cardioplegic solution number 1 (STH1) or number 2 (STH2), and then maintained in
      a state of hypothermic (15 degrees C) ischaemia for 6 or 8 h. Hearts in the multi
      dose groups received cardioplegia every hour (2 min at 15 degrees C). At the end
      of ischaemia all hearts were reperfused (60 +/- 2 mmHg perfusion pressure) for 40
      min with blood from a support pig. Systolic and diastolic functions were assessed
      with an intraventricular balloon, and endothelial and smooth muscle functions by
      measuring the response to infusions of defined concentrations of acetylcholine
      (8, 16 and 32 micrograms/min) and glyceryl trinitrate (40, 80 and 160
      micrograms/min). Hearts (n = 9) not subjected to ischaemia were perfused for the
      same duration to act as aerobic controls. At the end of the perfusion period,
      hearts were frozen and taken for metabolite analysis. After 8 h ischaemia, the
      recovery of left ventricular developed pressure was greatest in the multi-dose
      STH1 and single-dose STH2 groups (113 +/- 6 and 117 +/- 6 mmHg, respectively, v
      128 +/- 9 mmHg in aerobic controls, at an end-diastolic pressure of between 3 and
      9 mmHg; P = N.S.) and the poorest in the single-dose STH1 group (92 +/- 5 mmHg; P
      < 0.05 v controls). The recovery of diastolic function was greatest in the multi
      dose STH2 group and again poorest in the single-dose STH1 group (left ventricular
      end-diastolic pressure 1 +/- 2 and 30 +/- 10 mmHg, at a ventricular volume of 3.0
      ml, v -1 +/- 1 mmHg in aerobic controls). Vascular responses to acetylcholine and
      glyceryl trinitrate and the myocardial high-energy phosphates content were better
      preserved in multi-dose groups and with STH2. Inter-group differences were less
      when the duration of ischaemia was reduced to 6 h. In conclusion, the neonatal
      pig heart was best preserved with multi-dose cardioplegia and STH2 was more
      efficacious than STH1. However, not all indices were optimally protected by multi
      dose STH2. Thus, the best protection of systolic function was obtained with
      multidose STH1 and this was followed by single-dose STH2. Diastolic function was
      best preserved with multi-dose STH2 as were vascular function and high-energy
      phosphates.

PMID- 8523453
TI  - Ryanodine induced block of a cloned human cardiac potassium channel.
AB  - The effects of ryanodine in a cloned human cardiac potassium channel (hKvl.5)
      expressed in a stable mouse L cell line was studied using whole cell voltage
      clamp technique. Ryanodine in a dose dependent manner (10(-7) - 10(-5) M) reduced
      the peak current as well as the current at the end of a 250 ms pulse. Dose
      response data fitted to a Hill equation yielded IC50 of 1.2 microM. The degree of
      block was not voltage dependent. Peak current was reduced from 43.6 +/- 12.5% at
      10(-5) M to 11.3 +/- 4.8% at 10(-7) M ryanodine. Ryanodine reduced the tail
      current amplitude without changing the time course relative to the control. The
      inhibition was only partially reversible at concentrations below 10(-6) M.

PMID- 8523454
TI  - Brief, intermediate and prolonged ischemia in the isolated crystalloid perfused
      rat heart: relationship between susceptibility to arrhythmias and degree of
      ultrastructural injury.
AB  - Isolated Langendorff-perfused rat hearts were used to assess susceptibility to
      reperfusion-induced arrhythmias after different durations of ischemia in
      relationship to structurally related impairment of heart function, and to examine
      whether phase two ischemia-induced arrhythmias occur in crystalloid perfused
      hearts. This was achieved by subjecting the hearts to 5 min reperfusion following
      either sustained (240 min), intermediate (30 min), or brief (10 min) regional
      ischemia. Sustained ischemia induced little arrhythmogenesis upon reperfusion (no
      ventricular fibrillation) and impairment of recovery of coronary flow
      (approximately 64% of uninvolved zone flow). Electron microscopic investigation
      of the ischemic region revealed severe degenerative damage of the ultrastructure
      of cardiac myocytes and capillary endothelial cells. In contrast, reperfusion
      following brief ischemia caused all hearts to develop ventricular fibrillation
      (VF), accompanied by a persisting hyperemia throughout the course of reperfusion
      (flow 149 +/- 33% of that in the uninvolved zone after 1 min of reperfusion). In
      this group, myocardial ultrastructure exhibited negligible i.e., almost complete
      reversal of injury, upon reperfusion. Intermediate (30 min) ischemia led to a
      high incidence of reperfusion arrhythmias (92% of hearts developing VF) and
      modest hyperemia (flow 111 +/- 22% of that in the uninvolved zone after 1 min of
      reperfusion). Moderate ultrastructural alterations and their further
      deterioration upon reperfusion were observed in some but not all hearts in this
      group. During ischemia, phase 1 arrhythmias were common (57% of hearts developed
      VF during the first 30 min). However, phase 2 arrhythmias were absent during 120
      240 min ischemia in these isolated hearts. In conclusion sustained ischemia in
      the rat heart renders myocardium unviable with a consequent loss of
      susceptibility to reperfusion arrhythmias. Phase 2 ischemia-induced arrhythmias
      do not occur in this model, implicating an intact autonomic nervous system and/or
      circulating factors from blood (e.g., neutrophils) in phase 2 arrhythmogenesis.

PMID- 8523455
TI  - Tissue endothelin-1 levels in perfused rat heart following stimulation with
      agonists and in ischaemia and reperfusion.
AB  - The purpose of this study was to compare coronary and interstitial endothelin-1
      (ET-1) levels in perfused rat hearts under several experimental conditions,
      because the cardiac tissue concentration of ET-1 is not clear. Hearts were
      perfused in an upside-down position with a colloid-free buffer at a constant flow
      rate of 9 ml/min/g heart wet weight, and immunoreactive ET-1 was determined in
      timed collections of coronary effluent and interstitial transudate produced by
      the ventricles and appearing on their surface. Basal ET-1 release into effluent
      was 0.26 +/- 0.007 pg/min/g, and 0.005 +/- 0.0012 pg/min/g in transudate. Basal
      ET-1 concentration was 0.11 +/- 0.005 pg/ml (transudate) and 0.03 +/- 0.002 pg/ml
      (effluent), indicating four-fold higher transudate than effluent levels (P <
      0.05). Following perfusion of hearts with collagenase to remove endothelial
      cells, ET-1 release into effluent was reduced to one-third and completely
      abolished in transudate, indicating that the peptide originated from the vascular
      endothelium. Perfusion of hearts with angiotensin II (0.1 mumol/l) or thrombin (5
      U/ml) increased coronary perfusion pressure and ET-1 secretion, but little
      affected the transudate/effluent ET-1 concentration ratio (5.5 and 3.2,
      respectively). When coronary flow was reduced to ischaemic level (1 ml/min/g over
      several hours), ET-1 secretion rates into effluent were decreased by 55-65%, but
      increased three- to four-fold on reperfusion at normal flow (P < 0.05). The ET-1
      concentrations in both fluids were still always below 1 pg/ml. No change in
      coronary perfusion pressure compared to time-matched normoxic controls was
      observed. In the presence of the ET-1 converting enzyme inhibitor, phosphoramidon
      (1.7 mumol/l), ischaemia-induced increases of ET-1 secretion were attenuated, and
      this was accompanied by a time-dependent rise in coronary perfusion pressure up
      to 60% (P < 0.05). These are the first measurements of endogenous cardiac tissue
      ET-1 levels; they do not support a vasoconstrictor (pro-ischaemic) action of
      endogenous ET-1 in rat hearts following ischaemia/reperfusion, but rather point
      to a possible vasodilator role of the peptide under these conditions.

PMID- 8523456
TI  - Effect of ischemia and ischemia--reperfusion on ryanodine binding and Ca2+ uptake
      of cardiac sarcoplasmic reticulum.
AB  - The effect of 15 min of global, normothermic ischemia on 3H-ryanodine binding and
      the oxalate-supported Ca2+ uptake of cardiac sarcoplasmic reticulum (SR) was
      investigated in parallel using ventricular homogenates of isolated perfused rat
      hearts. Ischemia increased the Ca2+ efflux under the uptake assay conditions, as
      demonstrated by the greater stimulation of Ca2+ uptake by high concentrations of
      ryanodine (+RY) to close the SR Ca2+ channel. This effect was partially reversed
      by reperfusion. Ischemia depressed Ca2+ uptake rate -RY at free [Ca2+] of 0.4
      microM and above, while the depression + RY was significant only above 10 microM
      Ca2+. We tested the hypothesis that inhibition of the Ca-ATPase alone, by adding
      thapsigargin or cyclopiazonic acid, could reproduce the effects of ischemia on
      the homogenate Ca2+ uptake rate. Thapsigargin or cyclopiazonic acid
      proportionally depressed Ca2+ uptake rate +RY and -RY and produced distinctly
      different effects of ischemia. Ischemia did not change the Bmax or Kd for
      equilibrium 3H-ryanodine binding, or the Hill coefficient or KCa for the [Ca2+]
      dependence of equilibrium 3H-ryanodine binding. The rate of ryanodine binding,
      measured under the uptake conditions, was increased by ischemia and further
      increased by reperfusion. The effect of ischemia on the rate and extent of
      equilibrium binding to the high-affinity ryanodine binding site were unrelated to
      the highly reproducible effects on SR Ca2+ uptake rates measured in the
      homogenate.

PMID- 8523457
TI  - Inhibition by verapamil and diltiazem of agonist-stimulated contractile responses
      in mammalian ventricular cardiomyocytes.
AB  - Secretin, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide
      (CGRP) each exert potent positive contractile responses directly in rat
      ventricular cardiomyocytes. However, the contractile-coupling mechanisms
      associated with these responses have not been determined. In the present study,
      the involvement of L-type calcium channels in the contractile responses elicited
      by each peptide has been investigated using the selective antagonists at L-type
      calcium channels, verapamil and diltiazem. Ventricular cardiomyocytes, isolated
      from the hearts of adult rats, were stimulated to contract at 0.5 Hz in the
      presence of CaCl2 (2 mM) and adenosine deaminase (5U/ml). Cardiomyocytes were pre
      incubated for 3 min prior to stimulation, in the absence of L-type calcium
      channel antagonist, and in the presence of verapamil (< or = 1 microM) or
      diltiazem (< or = 1 microM). Verapamil (< or = 1 microM) and diltiazem (< or = 1
      microM) inhibited the contractile responses elicited by isoprenaline (100 nM) and
      forskolin (40 microM), used as positive controls, significantly, and in a
      concentration-dependent manner, but did not inhibit significantly the contractile
      response elicited by phenylephrine (2 microM), which was employed as a negative
      control. Verapamil (< or = 1 microM) and diltiazem (< or = 1 microM) inhibited
      the contractile responses to secretin (20 nM) and VIP (20 nM) significantly, and
      in a concentration-dependent manner, but did not inhibit the contractile response
      to CGRP. These data indicate that the positive contractile responses to secretin
      and VIP in mammalian ventricular cardiomyocytes involve the influx of calcium ion
      via L-type calcium channels, while the positive contractile response to CGRP does
      not.

PMID- 8523458
TI  - Effect of endothelin-1 and its combination with adenosine on myocardial
      contractility and myocardial energy metabolism in vivo.
AB  - Contradictory results have been reported about the inotropic effects of the
      vasoconstrictive peptide endothelin-1 (ET-1). In contrast to in vitro
      experiments, in vivo studies could not demonstrate a positive inotropy of ET-1.
      It may be possible, that the direct positive inotropic effect of ET-1 observed in
      in vitro studies is counterbalanced in vivo by an indirect negative inotropy due
      to its coronar-constrictive effect. This study examined the hemodynamic and
      inotropic effects of 2500 ng ET-1/kg without and after pretreatment with the
      vasodilating nucleoside adenosine (0.5, 2.0, 5.0 mg ADO/kg/min). Data were
      compared with NaCl controls in open-chest rats during and after a 7-min infusion.
      Besides measurements in the intact circulation isovolumic measurements were
      carried out for quantification of myocardial contractility independently of
      peripheral vascular effects. We further examined the effect of ET-1 and its
      combination with 2.0 mg ADO/kg/min on myocardial high-energy phosphates (ATP,
      AMP, ADP, creatine phosphate). ET-1 causes a strong and longlasting
      vasoconstriction (+ 186% v preinfusion values), which is dose-dependently
      antagonized in part by ADO (+ 109%, + 136%, + 60%). While the maximum of the
      isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were
      unchanged with sole ET-1 (peak LVSP: +5%, peak dP/dtmax: -2%), these indexes of
      myocardial contractility were increased after pretreatment with ADO (peak LVSP:
      +11%, +13%, +4%; peak dP/dtmax: +9%, +20%, +10%) indicating a positive inotropic
      effect of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523459
TI  - The role of lipid peroxidation in menadione-mediated toxicity in cardiomyocytes.
AB  - The role of lipid peroxidation in menadione-mediated toxicity was studied in
      neonatal rat cardiomyocytes. Incubation of cardiomyocytes with menadione resulted
      in depleted cellular glutathione levels, increased intracellular Ca2+ and
      increased lipid peroxidation which all occurred prior to cell degeneration. Pre
      treatment of cells with cysteine suppressed the menadione-induced cell
      degeneration and prevented changes in glutathione levels, intracellular Ca2+, and
      lipid peroxidation. Pre-treatment of cells with fura-2 acetoxymethyl ester, a
      Ca2+ chelator, reduced menadione-induced cell degeneration and lipid peroxidation
      but it did not block cellular glutathione depletion. Pre-treatment of cells with
      deferoxamine mesylate, an iron chelator, also reduced both menadione-induced cell
      degeneration and lipid peroxidation; however, it did not prevent the menadione
      induced increase in intracellular Ca2+, nor the depletion of glutathione. Thus,
      the inhibition of menadione-induced lipid peroxidation by deferoxamine mesylate
      prevented cell degeneration even though intracellular Ca2+ remained elevated and
      glutathione remained depleted. The protective effects of deferoxamine mesylate
      and fura-2 AM on menadione's toxicity were inhibited by addition of FeCl3 to
      cells. Ferric ions did not inhibit the protective effect of cysteine. These data
      suggest that menadione-induced cardiomyocyte degeneration is directly linked to
      iron-dependent lipid peroxidation and less tightly coupled to elevation in
      intracellular Ca2+ or depletion of glutathione.

PMID- 8523460
TI  - Suppression of myocardial mitochondrial respiratory function in acute failing
      hearts made by a short-term Ca2+ free, high Ca2+ coronary perfusion.
AB  - We made acute cardiac failure in excised cross-circulated canine hearts by a new
      coronary perfusion protocol consisting of Ca2+ free Tyrode perfusion for the
      first 10 min, high Ca2+ (16 mmol/l) Tyrode perfusion for the next 5 min, and
      normal Tyrode perfusion for the last 5 min interrupting blood cross circulation.
      After 50 min from the blood recirculation, left ventricular contractility was
      stably depressed to 60% of control. We studied mechanoenergetics of these acute
      failing hearts for the next 1-3 h. Then, we prepared mitochondria from these
      excised failing hearts and the support dogs' normal hearts to examine their
      mitochondrial respiratory function by the respiratory control index (RCI) and the
      oxygen consumption rate in state III (State III O2). RCI and State III O2 were
      significantly smaller in the failing hearts than in the normal hearts. However,
      sham protocol consisting of normal Tyrode coronary perfusion for 20 min did not
      affect RCI and State III O2. These results revealed that the mitochondrial
      respiratory function was moderately impaired in these acute failing hearts made
      by the new short-term Ca2+ intervention. However, no ultrastructural injuries of
      mitochondria were detected in these failing hearts.

PMID- 8523461
TI  - Characterization of inducible nitric oxide synthase expression in endotoxemic rat
      cardiac myocytes in vivo and following cytokine exposure in vitro.
AB  - Lipopolysaccharide (LPS) treatment results in widespread expression of the
      inducible isoform of nitric oxide (NO) synthase (iNOS). Although there is
      evidence for the expression of iNOS in heart tissue, regulation of myocardial
      iNOS expression is not known. To determine the time course and degree of iNOS
      induction in the adult heart, we examined iNOS mRNA expression and enzyme
      activity in (1) rat left ventricular tissue after LPS treatment in vivo, and (2)
      cultured, long-term rat cardiac myocytes maintained in serum and exposed to
      interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma, and/or LPS.
      iNOS mRNA was detected by Northern blot analysis and in situ hybridization. iNOS
      enzyme activity was measured in extracts of whole heart, and nitrate and nitrite
      (the stable end-products of NO) accumulation was quantified in cardiomyocyte
      culture media. iNOS mRNA was not detected in untreated hearts or cultured
      myocytes but was apparent within 3 h in both hearts obtained from LPS-treated
      animals and in cytokine-treated myocytes. In whole heart, iNOS mRNA expression
      peaked by 6 h after LPS and declined by 12 and 24 h. In situ hybridization
      demonstrated perinuclear localization of iNOS mRNA in both cardiac vascular
      smooth muscle and myocytes with maximal expression at 6 h after LPS injection. In
      cardiac myocytes, iNOS expression was maximal at 12 to 24 h, persisted through 48
      h, and was partially inhibited by dexamethasone. Interferon-gamma was the most
      potent single cytokine with regards to myocyte iNOS induction. Nitric oxide
      release in cytokine-stimulated cardiac myocytes was largely in the form of
      nitrate and was associated with increased glucose uptake and lactate release; the
      former finding indicates that NO interacts with myocardial heme proteins and/or
      oxyradicals, while the latter suggests inhibition of oxidative metabolism.
      Although non-myocardial cells may significantly contribute to iNOS expression in
      whole heart tissue, significant iNOS expression and NO production also take place
      within the myocyte. Induced NO production may regulate myocardial perfusion and
      impair myocardial function and metabolism.

PMID- 8523462
TI  - The effects of long-term treatment with eicosapentaenoic acid and docosahexaenoic
      acid on hypoxia/rexoygenation injury of isolated cardiac cells in adult rats.
AB  - N-3 polyunsaturated fatty acids have been epidemiologically demonstrated to
      decrease the incidence of ischaemic heart disease. The present study was
      undertaken to examine the effects of long-term treatment with eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) on hypoxia/reoxygenation injury of
      isolated adult rat cardiomyocytes. Rats, fed with standard rat chow, were treated
      with 100 to 1000 mg/kg/day EPA or 1000 mg/kg/day DHA for 4 weeks and their
      cardiomyocytes were isolated by collagenase treatment. The cardiomyocytes,
      approximately 90% of which were rod-shaped, were subjected to 150-min hypoxia/15
      min reoxygenation, and their survivals at the ends of hypoxia and reoxygenation
      were determined. Treatment with either 1000 mg/kg/day of EPA or DHA resulted in a
      significant increase in the survival of the cardiomyocytes (39.9 +/- 1.1 and 38.3
      +/- 3.0%, n = 14 and 8, respectively v 26.7 +/- 1.6%, n = 8, for untreated
      group). Treatment with EPA increased eicosapentaenoic (377% increase), oleic (25%
      increase) and linoleic acid (37% increase) contents in the myocardial total
      phospholipids without changes in the total phospholipid content, whereas
      treatment with DHA did not increase DHA incorporation into the myocardial
      phospholipids. The results suggest that EPA and DHA protect the myocardial cells
      against hypoxia-reoxygenation-induced injury. Although alterations in myocardial
      phospholipid composition were observed by treatment with EPA or DHA, the primary
      mechanism underlying the benefit of EPA or DHA intake is unlikely to be related
      to increased incorporation of their own fatty acids into the myocardial
      phospholipids, or the mechanism may be different in each n-3 unsaturated fatty
      acid employed.

PMID- 8523463
TI  - Expression of cytokine-induced neutrophil chemoattractant in rat cardiac
      myocytes.
AB  - Accumulation and adhesion of leukocytes to cardiac myocytes play important roles
      in the pathogenesis of inflammation-mediated myocardial injury such as
      ischaemia/reperfusion and myocarditis. The involvement of leukocyte chemotactic
      factors has been speculated in these processes. We investigated the expression of
      cytokine-induced neutrophil chemoattractant (CINC) in rat cardiac myocytes. CINC
      is a rat equivalent of human interleukin-8. On exposure to interleukin-1 alpha
      (IL-1 alpha), cultured neonatal rat cardiac myocytes released appreciable levels
      of CINC both dose- and time-dependently. Tumor necrosis factor-alpha and
      lipopolysaccharide also significantly increased CINC accumulation in the culture
      supernatant. CINC mRNA expression was not observed in unstimulated myocytes,
      however, the expression was markedly induced by exposure to IL-1 alpha with a
      peak elevation at 3 h. Potent chemotactic activity for neutrophils was detected
      in the supernatant of cultured rat cardiac myocytes by stimulation with IL-1
      alpha. This IL-1 alpha-induced chemotactic activity was significantly inhibited
      by polyclonal anti-CINC antiserum. Addition of dexamethasone, genistein,
      actinomycin D or cycloheximide significantly suppressed the IL-1 alpha-induced
      CINC accumulation. Under hypoxia (95%N2 + 5%CO2), CINC accumulation was increased
      in a time-dependent manner, and reoxygenation after hypoxia further intensified
      CINC accumulation. This hypoxia reoxygenation-induced CINC expression was
      significantly inhibited by pretreatment with dexamethasone. In conclusion,
      inflammatory stimuli induce the expression of CINC in rat cardiac myocytes, which
      may lead to myocardial injury via accumulation and activation of neutrophils.

PMID- 8523464
TI  - Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with
      hypertrophic cardiomyopathy.
AB  - We have searched for mutations in alpha-tropomyosin gene in 50 Japanese patients
      with hypertrophic cardiomyopathy (HCM) by means of polymerase chain reaction
      (PCR)-single strand conformation polymorphism (SSCP) analysis. Two missense
      mutations of the alpha-tropomyosin gene were detected in Japanese patients with
      familial HCM. Sequencing analysis revealed a C to T transition at codon 63
      leading to a replacement of Ala with Val residue, and a G to A transition with
      replacement of Asp by Asn at codon 175. These missense mutations were found at
      residues which were markedly conserved across the species, and have been reported
      to interact with troponin T. This is the first report on a mutant alpha
      tropomyosin gene in a Japanese population. Familial HCM is a genetically
      heterogeneous disease in Japanese patients, similar to that reported in Caucasian
      kindreds.

PMID- 8523465
TI  - Antioxidant effects of pyruvate in isolated rat hearts.
AB  - Sprague-Dawley rat hearts were perfused under constant flow conditions, and a
      balloon was inserted into the left ventricle to measure heart rate (HR) and left
      ventricular pressures. Left ventricular generated pressure (LVGP) was calculated
      as peak systolic minus end diastolic pressure. Three substrate groups, pyruvate
      (5 mM), glucose (15 mM) and octanoate (0.5 mM), were employed. Oxidative stress
      was induced by perfusion with tertiary-butyl hydroperoxide (tBHP, 0.35 mM, 12
      min) followed by 25 min of perfusion with control buffer. Hearts perfused with
      pyruvate showed no significant decrease in contractile function following tBHP
      treatment (HR x LVGP = 17666 +/- 585 mmHg/min, initial: 16414 +/- 2083 post-tBHP
      treatment). Glucose-perfused hearts had an intermediate decrease in function
      (19174 +/- 828 mmHg/min, initial; 4379 +/- 2083 post-tBHP), while octanoate
      perfused hearts recovered no contractile function. Peak release of LDH was lowest
      in hearts perfused with pyruvate (115 +/- 17 mU/g wet wt/min), intermediate in
      glucose-perfused hearts (1575 +/- 380) and highest in octanoate-perfused hearts
      (3074 +/- 499). Thiobarbituric acid reactive substances (TBARS) were unchanged in
      hearts perfused with pyruvate (16.2 +/- 5 nmoles/g wet wt), but increased
      significantly in glucose-perfused hearts (36.1 +/- 1) and in octanoate-perfused
      hearts (45.5 +/- 9). Total glutathione levels were unchanged in hearts perfused
      with pyruvate (753 +/- 68 nmoles/g wet wt), but significantly decreased in
      glucose-perfused hearts (594 +/- 68) and in octanoate-perfused hearts (445 +/-
      38) following tBHP-treatment. Pyruvate significantly reduced oxidative injury. In
      contrast, glucose provided a small reduction in injury while octanoate-perfused
      hearts had the most severe injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523466
TI  - The relation between extracellular potassium concentration and pH in the border
      zone during regional ischemia in isolated porcine hearts.
AB  - During regional ischemia gradients of extracellular potassium concentration
      ([K+]o) and extracellular pH (pHo) exist. In globally ischemic papillary muscles
      increased PCO2 causes a rise in [K+]o. We studied whether pHo and [K+]o are
      causally related during acute regional ischemia in the isolated blood-perfused
      pig heart. Multiple pH- or K(+)-sensitive electrodes were inserted in the left
      ventricular midmyocardium. Local electrograms and ionic data were simultaneously
      acquired. Regional ischemia was produced by interrupting left anterior descending
      (LAD) artery flow (10 min). Up to 5 mm from the electrophysiological border the
      pH-K relation deviated from that in the central ischemic zone. Respiratory
      acidosis (pH about 7.10) of the perfusate in the presence of LAD-ischemia caused
      acidification of the ischemic border zone without a local change in [K+]o. We
      conclude that pHo changes are not related to changes of intramural [K+]o in the
      lateral border zone during regional ischemia.

PMID- 8523467
TI  - Could HEPES contribute to the myocardial prooxidant effects of adventitious redox
      active metals in Krebs-Henseleit buffer?

PMID- 8523468
TI  - Arsine toxicity: chemical and mechanistic implications.

PMID- 8523469
TI  - Pulmonary response of mice to fiberglass: cytokinetic and biochemical studies.
AB  - It has been suggested that glass fibers in the respirable size range may pose a
      health hazard similar to asbestos because of the similarities in physical
      characteristics. To compare the pulmonary cell response with that described
      earlier with crocidolite asbestos, we administered a milled fiberglass sample to
      mice by intratracheal instillation. Little effect was seen at a dose of 0.1 mg,
      but at 1 mg there was epithelial injury and an inflammatory cell response
      concentrated at bronchiolar-alveolar duct regions. Cellular incorporation of
      tritiated thymidine showed that repair of both bronchiolar and alveolar
      epithelium occurred rapidly. This was followed by an extended increase in cell
      labeling, particularly in peribronchiolar fibroblasts, from 2 to 8 wk after fiber
      instillation. Granulomas formed at this site and later there was morphologic
      evidence of fibrosis, which was confirmed biochemically by a significant increase
      in lung collagen at 4-16 wk. Although 10 times higher dose is required, the
      results show that the lung response to fiberglass in this experimental system is
      similar to that described previously for crocidolite asbestos; the sites of cell
      injury and repair are the same, and the subsequent fibrotic response produces
      small airway disease.

PMID- 8523470
TI  - Grain dusts and grain plant components vary in their ability to recruit
      neutrophils.
AB  - Occupational exposure to grain dusts can cause bronchitis, particularly to grain
      sorghum dust. Bronchitis is associated with the presence of increased numbers of
      neutrophils. To determine how grain dusts could cause neutrophil recruitment to
      the airways, extract of whole-grain sorghum, corn, and soybean dusts and of
      pulverized components of these plants were made with Hanks balanced salt solution
      (HBSS) and used in direct neutrophil chemotaxis experiments. The glume of the
      grain sorghum plant, the structure holding the seeds in place, caused the
      migration of the greatest number of neutrophils compared to HBSS [132 +/- 7 vs.
      60 cells/high-power field (hpf) +/- 2 SEM, p < .001], followed by whole-grain
      sorghum dust (121 +/- 5 cells/hpf). Next, bovine bronchial epithelial cells
      (BBECs) were obtained from fresh lungs and grown to near confluence before
      challenge with a 10% solution of grain dust and grain plant extracts. The grain
      sorghum glume and whole-grain sorghum dusts caused release of the greatest amount
      of neutrophil chemotactic activity (NCA) from BBECs compared to the medium M199
      negative control (141 +/- 6 and 153 +/- 7, respectively, vs. 64 cells/hpf +/- 3
      SEM, p < .001). The ability to cause neutrophils to migrate by direct and
      indirect means did not correlate with levels in the grain dusts of endotoxin,
      which is known to cause release of NCA from bronchial epithelial cells.
      Therefore, this article describes additional mechanisms by which grain dusts can
      cause pulmonary inflammation and that are independent of endotoxin levels.

PMID- 8523471
TI  - Acid-labile adducts to protein can be used as indicators of the cysteine S
      conjugate pathway of trichloroethene metabolism.
AB  - Covalent binding of radiolabel to tissue proteins following [14C]trichloroethene
      (TRI) exposure has been used as a measure of TRI activation. Gross binding of 14C
      label does not differentiate between alternate routes of metabolism and can be
      confounded when there is significant metabolic incorporation of radiolabel. We
      examined the covalent association of 14C label to hepatic and renal proteins in
      male F344 rats and B6C3F1 mice following oral treatment with [14C]TRI and three
      metabolites of TRI: [14C]trichloroacetate (TCA), [14C]dichloroacetate (DCA), and
      [14C]dichlorovinylcysteine (DCVC) in vivo. Association of radiolabel from
      [14C]TRI with hepatic proteins reached a maximum at 2 and 4 h in mouse and rat
      hepatic proteins, respectively. Association of radiolabel with renal proteins
      reached a maximum at 8 h in both species. An approach was developed based upon
      formation of protein adducts that release acetate and monochloroacetate (MCA) on
      acid hydrolysis. These adducts were found to be specifically associated with the
      activation of DCVC to reactive intermediates. Acetate and MCA were identified by
      using two different conditions of high-performance liquid chromatography (HPLC)
      separation with differing selectivity. Diethylmaleate and aminooxyacetic acid
      pretreatment inhibited the formation of these adducts from TRI, consistent with
      requirements for glutathione and beta-lyase. No evidence of these adducts was
      detected following [14C]TCA and [14C]DCA treatment. Renal acid-labile adduct
      formation from 25 mg/kg DCVC was approximately 12-fold greater in male B6C3F1
      mice than in male F344 rats. They accounted for 7.8 and 4.6% of the total adducts
      to renal protein in rats and mice, respectively. Acid-labile adducts formed from
      1000 mg/kg TRI were approximately two times greater in mice than rats. In this
      case, they accounted for 1.4 and 3.3% of the total adduct formed in renal
      proteins from TRI (corrected for metabolic incorporation), respectively. This
      greater dilution of adducts associated with DCVC in renal proteins of the rat
      suggests that covalent binding of TRI has less specificity for the DCVC pathway
      in rats than in mice.

PMID- 8523472
TI  - Renal activation of trichloroethene and S-(1,2-dichlorovinyl)-L-cysteine and cell
      proliferative responses in the kidneys of F344 rats and B6C3F1 mice.
AB  - Covalent binding of reactive intermediates formed by renal beta-lyase activation
      of S-(1,2-dichlorovinyl)-L-cysteine (DCVC) has been suggested to be responsible
      for the greater renal sensitivity of rats than mice to the carcinogenic effects
      of chronic treatment with trichloroethene (TRI). Previous work demonstrated that
      the activation of DCVC results in acid-labile adducts to protein that can be
      distinguished from adducts formed by other pathways of TRI metabolism. By
      analyzing acid-labile adduct formation, the relationship between DCVC formation
      and activation from TRI and increases in rates of cell division in the kidneys of
      male F344 rats and B6C3F1 mice could be investigated. The delivered dose of DCVC
      from an oral dose of 1000 mg/kg TRI was approximately six times greater in rats
      than mice. However, renal activation of DCVC in mice was approximately 12 times
      greater than in rats. Therefore, the overall activation of TRI was about two
      times greater in mice than rats. Induction of cell replication in liver and
      kidney following doses of 1, 5, or 25 mg/kg DCVC or 1000 mg/kg TRI was also
      measured through the use of miniosmotic pumps that delivered BrdU subcutaneously
      for 3 d. Acid-labile adduct formation from DCVC and TRI displayed a consistent
      relationship with increased cell replication in mice and between mice and rats.
      Both cell replication and acid-labile adduct formation in rats given 25 mg/kg
      DCVC were approximately equal to that observed in mice given 1 mg/kg. Increased
      cell replication was not observed in rats receiving 1 or 5 mg/kg DCVC or 1000
      mg/kg TRI, nor were there histological signs of nephrotoxicity. Thus, net
      activation of TRI by the cysteine S-conjugate pathway was found to be greater in
      mice than rats and these findings appeared related to differences in cell
      proliferative responses of the kidneys of the two species. Based on these data,
      it would appear that other factors must contribute to the greater sensitivity of
      the rat to the induction of renal carcinogenesis by TRI.

PMID- 8523473
TI  - Risk assessment, life history strategies, and turtles: could declines be
      prevented or predicted?
AB  - The process of ecological risk assessment should involve the ability to predict
      adverse outcomes of particular environmental contaminants or human intrusions.
      Ecological risk assessment generally focuses on populations, communities, and
      ecosystems, rather than on individual health. We explore the importance of life
      history strategies of aquatic turtles to their risk from environmental
      contaminants and other human activities using three examples: the wood turtle
      Clemmys insculpta, a freshwater species; the diamondback terrapin Malaclemys
      terrapin, a littoral species; and marine turtles as a group. These turtles are
      partly herbivorous and are at low or intermediate levels on the food chain, yet
      are particularly vulnerable due to their life history strategies of being long
      lived with relatively low survival of young. They suffer a variety of natural
      mortality factors that include predation, starvation, and disease, as well as
      inundation and destruction of nesting beaches and their eggs by storms. Yet they
      also face a number of anthropogenic hazards, including toxic chemicals and
      floatables (plastics); capture for food, other products, and pets; incidental
      mortality in fishing gear; disturbance while nesting or moving on land; injuries
      or death by collision with boats; and increased predator exposure because of
      humans. The three turtle species (or groups of species) examined have experienced
      these natural and anthropogenic pressures differentially, with resultant
      differences in the rates of population declines. Because they are lower on the
      food chain than other obligate carnivores, they are less vulnerable to toxics,
      and to date, toxics seem a relatively inconsequential environmental risk to
      turtles.

PMID- 8523474
TI  - Insidious effects of a toxic estuarine dinoflagellate on fish survival and human
      health.
AB  - The estuarine dinoflagellate Pfiesteria piscicida gen. et sp. nov. produces
      exotoxin(s) that can be absorbed from water or fine aerosols. Culture filtrate
      (0.22 microns porosity filters, > 250 toxic flagellated cells/ml) induces
      formation of open ulcerative sores, hemorrhaging, and death of finfish and
      shellfish. Human exposure to aerosols from ichthyotoxic cultures (> or = 2000
      cells/ml) has been associated with narcosis, respiratory distress with asthma
      like symptoms, severe stomach cramping, nausea, vomiting, and eye irritation with
      reddening and blurred vision (hours to days); autonomic nervous system
      dysfunction [localized sweating, erratic heart beat (weeks)]; central nervous
      system dysfunction [sudden rages and personality change (hours to days), and
      reversible cognitive impairment and short-term memory loss (weeks)]; and chronic
      effects including asthma-like symptoms, exercise fatigue, and sensory symptoms
      (tingling or numbness in lips, hands, and feet; months to years). Elevated
      hepatic enzyme levels and high phosphorus excretion in one human exposure
      suggested hepatic and renal dysfunction (weeks); easy infection and low counts of
      several T-cell types may indicate immune system suppression (months to years).
      Pfiesteria piscicida is euryhaline and eurythermal, and in bioassays a nontoxic
      flagellated stage has increased under P enrichment (> or = 100 micrograms SRP/L),
      suggesting a stimulatory role of nutrients. Pfiesteria-like dinoflagellates have
      been tracked to fish kill sites in eutrophic estuaries from Delaware Bay through
      the Gulf Coast. Our data point to a critical need to characterize their chronic
      effects on human health as well as fish recruitment, disease resistance, and
      survival.

PMID- 8523475
TI  - Proceedings of the 5th World Congress for the World Federation of Associations of
      Clinical Toxicology Centers and Poison Control Centers. Taipei, Taiwan, November
      8-11, 1994.

PMID- 8523476
TI  - The prevention of drug abuse--state of the art and directions for future actions.
AB  - Based on a public health model, three types of strategies to prevent drug abuse
      can be discerned: primary, secondary and tertiary prevention. Primary prevention
      programs (anticipation and prevention of the occurrence of drug abuse) have
      mostly been directed to elementary grade school children in general. As knowledge
      about genetic predisposition increases, early developmental periods are
      increasingly plastic, and substance abuse is now beginning at earlier ages.
      Prophylactic interventions need to focus on childhood high-risk groups. With
      respect to secondary prevention (aiming at the discontinuation of infrequent drug
      use) the stage (or stepping-stone) hypothesis is currently being challenged.
      Continuation is mainly a function of the type of drug as well as social and
      personality factors. Progression to higher-rank drugs depends mainly on the
      intensity of prior drug use. Comorbid psychiatric diseases are increasingly
      recognized and tractable. As in primary prevention the focus of secondary
      prevention shifts from sociocultural influences to the individual at risk.
      Regarding tertiary prevention (preventing the retaking of substances after
      achieving abstinence), research evaluating programs for the treatment of abuse of
      alcohol and other drugs indicates a limited staying power. Recent insights in the
      psycho- and neurobiologies of addictive behavior and in the psychopharmacological
      properties of alcohol and other drugs provide clinicians with new pharmacological
      tools to prevent relapse.

PMID- 8523477
TI  - The development of a broad-spectrum toxicology screening program in Taiwan.
AB  - Our institute serves as a centralized clinical laboratory for municipal and
      private hospitals in Taipei, a major international metropolis in the Asian
      region. Two key considerations leading to the development of our toxicology
      program are: a large number of foreign visitors and local residents returning
      from overseas trips may bring in chemicals which are less commonly seen in this
      region; and the lack of readily available assays for a large percentage of
      commonly used medicines, including prescription and over-the-counter drugs. Our
      toxicology screening program addresses the needs of both the Emergency Department
      Drug Screening and Drug of Abuse Screening. In Emergency Department Drug
      Screening, REMEDi HS is used as the general screening method. In Drug of Abuse
      Screening, the TDx is used for the initial screening of amphetamine-like
      substances and opiates, followed by REMEDi HS for the confirmation of positive
      samples. Emergency Department data collected at our institute over one year
      (September 1992 to August 1993) identified 57 different drugs in 713 samples.
      Opiates, narcotics and central stimulants accounted for 24% of the encountered
      drugs. Presently, there is no extensive reporting of misuse of benzodiazepines in
      this region. The detection of herbal ingredients like ephedrine and
      methylephedrine (from the Ma-Huang plant) in patient samples illustrates a large
      area often overlooked by western toxicology.

PMID- 8523478
TI  - Severe rhabdomyolysis mimicking transverse myelitis in a heroin addict.
AB  - Heroin addiction is known to cause various medical and neurological
      complications. We report here a case of rhabdomyolysis following heroin abuse, in
      which a neurological lesion mimicking transverse myelitis was also noted. A 29
      year-old man was found comatose in a kneeling position one day after a heroin
      overdose. On admission, he was awake, yet with total paralysis of his lower legs.
      Physical examination revealed marked swelling and tenderness of the four limbs,
      especially the lower extremities. Deep tendon reflexes and positional sense were
      absent in both legs; however, pin-prick sense was preserved. Transverse myelitis
      or spinal cord vasculitis was the initial working diagnosis. Laboratory tests
      disclosed significantly elevated creatinine kinase of 146289 U/L. Though
      suffering transient acute renal failure, his neurological abnormalities gradually
      improved over four weeks and a left foot drop was the only residual lesion at
      discharge. Rhabdomyolysis, a well defined complication following heroin use, may
      also cause concomitant neurological symptoms, for which careful differential
      diagnosis is warranted. With the increasing number of heroin addicts in Taiwan,
      more cases with rhabdomyolysis-induced neurological symptoms may be observed in
      the future.

PMID- 8523480
TI  - The role of the clinical toxicologist in chemical and environmental accidents.

PMID- 8523479
TI  - Use and abuse of benzodiazepines in Hong Kong 1990-1993--the impact of regulatory
      changes.
AB  - To control benzodiazepine abuse in Hong Kong, the Government's Pharmacy and
      Poisons Board reclassified benzodiazepines as Dangerous Drugs in October 1990.
      Apart from formal prescriptions, detailed records were then required for the
      supply and dispensing of these drugs. These regulations were applied initially
      only to brotizolam, triazolam and flunitrazepam, and were extended in January
      1992 to include all benzodiazepines. The impact of these regulatory changes on
      benzodiazepine use has been studied by analyzing the sales patterns of seven
      benzodiazepines between 1990-1993. In 1991, the sales of flunitrazepam and
      triazolam fell, but the sales of five unrestricted benzodiazepines increased. In
      1992-1993, the sales of all but one of the benzodiazepines fell. Comparing 1993
      to 1990, the fall in sales was particularly marked for triazolam,
      chlordiazepoxide and flunitrazepam. A regulation requiring the use of proper
      prescriptions and detailed records for the supply and dispensing of
      benzodiazepines, appears to have curbed, at least partially, their abuse in Hong
      Kong.

PMID- 8523481
TI  - Management of chemical disaster victims.
AB  - Following a hazardous chemical accident, early critical care life support is
      crucial to minimizing potential morbidity and mortality (1). Providing effective
      care to victims, however, depends on the nature of the incident, the number of
      victims affected, the availability of medical care, the coordination of rescue
      efforts, the available modes of evacuation, and the availability of post
      evacuation tertiary care. The goal in mass casualty scenarios is to minimize
      mortality and morbidity. Consequently, the most basic emergency response must
      include a method for assessing the incident, the extent of injury to victims,
      methods for determining which victims will receive treatment first, and what
      types of treatment will be given during the various stages of the incident. The
      basic need to handle hazardous chemical incident victims exists regardless of the
      environment in which the incident occurs, or whether small or large numbers of
      victims are involved.

PMID- 8523482
TI  - Application of biological monitoring to the diagnosis of poisoning.
AB  - Examples of cases in clinical medicine as well as occupational and environmental
      health studies are described to indicate the conditions under which reliable
      results for exposure assessment were obtained through biological monitoring.
      Biological monitoring is a solution-oriented practical approach. Four check
      points are described for effective biological monitoring, i.e., identification of
      the type of biological specimens available, selection of correct sampling time, a
      sensitive and selective analytical method, and interpretation based on a full
      knowledge of the metabolism.

PMID- 8523483
TI  - Toxicological and neuropsychological findings in patients presenting to an
      environmental toxicology service.
AB  - Patients presenting to an environmental toxicology service are frequently
      convinced that their multiple symptoms are caused by exposure to environmental
      toxicants. In order to evaluate the patients' hypotheses, 120 consecutive
      patients referred by health care providers to the environmental toxicology
      service for various symptoms were included in an open prospective study. The
      basic diagnostic procedure included an environmental toxicology questionnaire,
      psychological tests, a 45 minute interview, a physical examination and standard
      biomonitoring for cadmium, mercury, lead, lindane, hexachlorobenzene, DDT, DDE,
      DDD, and pentachlorophenol and a salivary test for mercury released from amalgam.
      Allergic disease was found in 42 patients. Nineteen of the 42 patients also had
      psychosomatic disorders. An unusually high release of mercury from amalgam
      fillings in the saliva test was found in six patients. An environmental toxic
      exposure was demonstrated in 19 patients (4 lead, 8 DDE, 6 mercury--most likely
      from broken thermometers, 1 neurotoxic alkyl naphtol derivatives). Ten of the 19
      patients had psychosomatic disorders and six had medical/neurological disorders.
      Only two patients had symptoms attributable to environmental exposure alone.
      Rather classical psychosomatic disorders were diagnosed in 83 patients. Of the 37
      patients without identifiable neuropsychological dysfunction, 18 had allergic
      disorders and 12 had other medical diagnoses. The diagnosis of a toxic
      environmental exposure should be performed in an integrated diagnostic approach
      covering environmental toxicology and medicine as well as psychosomatic medicine.

PMID- 8523484
TI  - Pulmonary collapse and pneumonia due to inhalation of a waterproofing aerosol in
      female CD-1 mice.
AB  - Waterproofing agents consist of mixtures of solvents, repellents and propellants.
      Because of a fatality and a number of acute respiratory illnesses in humans
      following the exposure to a waterproofing agent, the aerosol mixtures were tested
      in mice. Inhalation of the waterproofing agent resulted in pulmonary collapse and
      pneumonia in mice. By testing fractions of the waterproofing agent it was
      determined that the fluororesin repellents in the waterproofing agent were
      responsible for the acute respiratory illness. The water-repelling agent, such as
      fluororesin, may counteract the surfactant in the alveoli of the lung and cause
      diffuse pulmonary collapse followed by acute respiratory distress. The recent
      substitution of less toxic and environmentally more friendly solvents in
      waterproofing agents may facilitate fluororesin inhalation by increasing the
      amount of airborne aerosol and changing the diameter of the aerosol particles.
      This would explain the apparent recent increase of respiratory symptoms following
      the use of these agents. In this experiment the mice were exposed intermittently
      to overcome the CNS effects of the solvents.

PMID- 8523485
TI  - Increased body cadmium burden in Chinese women without smoking and occupational
      exposure.
AB  - To investigate the chronic low-level environmental cadmium and zinc exposure of
      Chinese women and find the relationships between these parameters and
      hypertension, 58 women without histories of smoking and occupational exposure
      were conducted into this cross-section study and divided into three groups: Group
      I: 24 normal healthy, Group II: 24 untreated essential hypertension, and Group
      III: 10 untreated nonessential hypertension women. The serum cadmium and daily
      urinary cadmium excretion of Group II (1.69 +/- 0.92 micrograms/L; 2.43 +/- 1.93
      micrograms/d) were significantly higher than those of Group I (0.88 +/- 0.92
      micrograms/L; 1.07 +/- 1.45 micrograms/d) as well as Group III (0.92 +/- 0.91
      micrograms/L; 0.19 +/- 0.23 micrograms/d). The ratio of urinary zinc
      (micrograms)/urinary creatinine (g) of Group II (865.99 +/- 460.54 micrograms/g)
      was higher than that of Group I (622.39 +/- 250.96 micrograms/g). The ratio of
      urinary cadmium concentrations (micrograms)/urinary creatinine (g) of all healthy
      Chinese women was 1.30 +/- 1.67 which is higher than that of other nations in the
      world except Japanese. After adjusting age and body mass index, we found mean
      arterial pressure positively correlated with serum cadmium in all subjects (p =
      0.0058). The mean arterial pressure also positively correlated with serum cadmium
      (p = 0.0017) as well as daily urinary cadmium excretion (p = 0.0088) in all women
      except the nonessential group. Both the ratios of urinary zinc
      (micrograms)/urinary creatinine (g) (p = 0.0165) and urinary cadmium
      (micrograms)/urinary creatinine (g) positively (p = 0.0246) related to mean
      arterial pressure in women of Group I and II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523486
TI  - Fatal encephalopathy after otoneurosurgery procedure with an aluminum-containing
      biomaterial.
AB  - Refractory status epilepticus was observed in two patients who underwent
      vestibular neurectomy. We investigated the relationship with the use of an
      aluminum containing bone cement during the procedure. Two patients developed
      focal and thereafter generalized seizures in the late postoperative period of
      vestibular neurectomy (respectively after 42 and 35 days). A cement (1 g aluminum
      calcium fluorosilicate) was used during the procedure to bridge bone defects.
      Both patients presented cerebrospinal fluid fistula. Investigations excluded
      common etiologies, in particular infections, and a toxic origin was suspected.
      Aluminum concentration was determined repeatedly in serum urine, cerebrospinal
      fluid and retroauricular fistula. The highest aluminum values were respectively
      in case 1 and 2, 112 and 63 micrograms/L for the cerebrospinal fluid, 495 and
      1440 micrograms/L for the fistula, 4.4 and 4.4 micrograms/L in serum.
      Desferrioxamine was used as chelating agent and aluminum elimination was analyzed
      in the urine. Status epilepticus became refractory to intensive care therapy. The
      patients never recovered normal consciousness. Case 1 died 143 days after the
      procedure and case 2 at 80 days from brain failure. Brain post-mortem examination
      was obtained in Case 2. Brain aluminum concentration was 2.5 micrograms/g (wet
      weight) (0.85 micrograms/g in a control non exposed cadaver). The cement (0.2 g)
      was incubated in vitro (16 h-37 degrees C) with the cerebrospinal fluid of a
      control patient (cerebrospinal fluid aluminum 8 micrograms/L): aluminum
      concentration reached 2750 micrograms/L. A close contact between an aluminum
      containing cement and the cerebrospinal fluid may have resulted in encephalopathy
      and fatal status epilepticus in these two patients.

PMID- 8523487
TI  - Stable isotopes of lead for source identification.
AB  - Lead is unique among all the metals in having variations among mining districts
      in the relative abundances of its stable (non-radioactive) isotopes. Since first
      described in 1927, many applications have been reported, mostly for geological
      uses. More recently archeological, environmental, bio-kinetic and public health
      uses have been found. The abundances of the four stable isotopes are usually
      determined with specialized mass spectrometry using rapid mass scanning cycles or
      multiple collectors. The relative abundances are commonly expressed as 206/204,
      206/207, and 206/208 atomic ratios. Precision of 0.5% for 206/204 and even better
      (0.03%) for the other pairs are obtainable. The three ratios co-vary strongly and
      depend on when the ore was formed. This provides a tracer for following a
      particular batch of lead, since the ratio can only change when the lead is mixed
      with a different lead. A major limitation of this method is that it is useful
      only to those problems where the potential sources are isotopically distinct and
      few in number. The covariance of the ratios usually allows for only two sources
      to be considered. Potential sources can often be ruled out.

PMID- 8523488
TI  - Stable isotope identification of lead sources in preschool children--the Omaha
      Study.
AB  - The objective was to determine, from analysis of the naturally occurring stable
      isotopes of lead, the relative contribution of food, handdust, housedust, soil
      and air lead to the absorbed (urinary) lead and the blood lead of children living
      in a former smelter city. A longitudinal 12 month study was conducted of 21
      children, 2 - 3 years of age, living in central Omaha, balanced for race, gender
      and socioeconomic status. Field clean samples were collected monthly of 24 hour
      duplicate diet, handwipe and urine, with quarterly blood lead, annual
      environmental lead, weekly air for total lead and 206Pb, 207Pb and 208Pb by
      thermal ionization/mass spectrometry with a 205Pb spike in a Class II laboratory.
      Despite residence in a smelter city each child had a unique isotopic ratio of
      handwipe, blood and urine lead, the latter being identical. There was no
      correlation of handwipe isotopic ratio with proximity to a lead emission source
      or to the decade of the housing stock. The isotopic ratio of the annual mean
      handwipe lead predicted 43% of the variance of the annual mean blood and urine
      lead ratio (r2 = .43; p = .001). Handwipe lead ratios correlated (p < or = .05)
      with those of the windowsills and air ducts. The mean isotopic ratios of blood
      and urine lead were lower than those of handwipe and food, consistent with a
      contribution by endogenous bone lead. Clean catch urine provides a noninvasive
      index of blood lead isotopic ratio in children, as in adults.

PMID- 8523489
TI  - The use of poison prevention and education strategies to enhance the awareness of
      the poison information center and to prevent accidental pediatric poisonings.
AB  - Poison information centers have traditionally served two major functions: the
      dissemination of poison information and poison prevention education. These
      functions facilitate the ultimate missions of the poison information centers
      which are to prevent accidental poisonings and to decrease morbidity and
      mortality associated with toxic exposures. Education must be directed at the
      potential and actual consumers of poison information centers services to prevent
      poisonings and to create awareness of how to use the poison information centers
      in the event of accidental or intentional poisoning. The target population can be
      identified from poison center statistics generated by the American Association of
      Poison Control Centers Toxic Exposure Surveillance System which define patient
      and caller demographics. Analysis of American Association of Poison Control
      Centers Toxic Exposure Surveillance System for ten years was used to identify the
      ten most common and ten most lethal poisons. This information indicates the most
      appropriate topics for education. These data also provide direction regarding
      poison center penetrance into specific geographic regions and identifies special
      needs of those individuals. Poison information centers are very costly to operate
      and the utilization of epidemiologic data can help to direct education efforts in
      the most cost-effective fashion.

PMID- 8523490
TI  - Acute poisonings in Poland.
AB  - The pattern of adolescent and adult poisonings in Poland is presented on the
      basis of the data from the regional toxicological centers (in-patient treatment
      centers). Drugs were the most frequent group of chemical substances, responsible
      for more than 50% of all admissions for acute poisonings. The second most
      frequent were alcohols with an increase in poisoning by alcohols to about 20% of
      total poisonings. Carbon monoxide was the third most frequent cause of
      poisonings. The percentages of poisonings by pesticides, corrosives and metal
      compounds have been reduced in recent years. The greatest number of lethal
      outcomes was also due to poisonings by alcohols, drugs, and carbon monoxide.

PMID- 8523491
TI  - Pesticide poisoning in the Asia-Pacific Region and the role of a regional
      information network.
AB  - Pesticide poisoning is an important cause of morbidity and mortality in many
      countries in the world. It has been estimated that 95% of fatal pesticide
      poisonings occur in developing countries, many of which are in the Asia-Pacific
      region. Agriculture based economies, easy availability of pesticides, poverty
      related socioeconomic problems, lack of adequate protective clothing, and limited
      treatment facilities are some of the factors contributing to the high morbidity
      and mortality. There is a lack of easily accessible information on pesticide
      related ill health in the countries of Asia-Pacific Region. Although Poison
      Centers are active in some countries, lack of resources is a major constraint on
      the provision of an efficient service. There are several intercountry projects
      and information networks in the region dealing with agriculture and environment
      but no such information facilities are available concerning pesticide poisoning.
      A Regional Pesticide Poisoning Information Network for the Asia-Pacific Region
      could disseminate information on pesticide related illness to any individual or
      institution via print and electronic media. Such a network could work towards
      close cooperation between all poisons centers and toxicologists in the region to
      reduce the rising morbidity and mortality from pesticide poisoning.

PMID- 8523492
TI  - The intermediate syndrome in organophosphate poisoning: an overview of
      experimental and clinical observations.
AB  - The intermediate syndrome of organophosphate poisoning arises in the time
      interval between the acute cholinergic crisis of fasciculations and muscle
      weakness and the delayed neuropathy attributed to inhibition of the neuropathy
      target esterase. The conclusions derived from salient experimental and clinical
      studies are that intermediate syndrome relates to the severity of poisoning not
      the specific organophosphate and to prolonged inhibition of acetylcholinesterase
      activity of the erythrocytes, brain and muscle endplate with pre and post
      synaptic impairment of neuromuscular transmission. It is not related to delayed
      neuropathy.

PMID- 8523493
TI  - Poisoning due to illegal use of carbamates as a rodenticide in Rio de Janeiro.
AB  - Carbamate insecticides (mainly aldicarb) are illegally commercialized as rat
      poisons and commonly used by the population of Rio de Janeiro for this purpose. A
      retrospective study concerning 189 cases (80 men, 109 women) of carbamate
      poisoning referred to the Poison Control Center of Rio de Janeiro throughout 1993
      is described. The causes of carbamate poisoning were suicide attempts (65%) and
      accidental ingestions (35%). The main signs and symptoms found (86%) were those
      related to the SLUDGE syndrome (increased salivation, lacrimation, urinary
      incontinence, diarrhea, gastrointestinal cramping and emesis) which were more
      commonly seen in adults than in children. Despite treatment with atropine, the
      case-fatality was 4%. It is concluded that there is a widespread risk of
      carbamate poisoning in Rio de Janeiro due to its clandestine use as a
      rodenticide. Effective measures by the government authorities should be
      implemented to stamp out the illicit commercialization of these compounds.

PMID- 8523494
TI  - A comparative study of direct hemoperfusion and hemodialysis for the removal of
      glufosinate ammonium.
AB  - BASTA is a herbicide containing glufosinate ammonium 18.5% and a surface-active
      agent. There were six fatalities in 34 cases of glufosinate ammonium poisoning
      reported by the Japan Poison Information Center. To evaluate efficacy in the
      removal of glufosinate ammonium from the blood, two bottles were prepared
      containing 600 mL of heparinized bovine blood with 1 mL or 3 mL of BASTA. Direct
      hemoperfusion or hemodialysis was performed for two hours at a flow rate of 50
      mL/min. The final glufosinate ammonium concentration of the blood bottle
      containing 1 mL of BASTA decreased to 96.9% of the initial concentration after
      direct hemoperfusion and to 0.5% after hemodialysis. The final glufosinate
      ammonium concentration of the bottle containing 3 mL of BASTA decreased to 62.2%
      after direct hemoperfusion and to 0.9% after hemodialysis. Hemodialysis is more
      effective than direct hemoperfusion for removal of glufosinate ammonium from
      blood.

PMID- 8523495
TI  - Glyphosate herbicide poisoning: use of a routine aminoacid analyzer appears to be
      a rapid method for determining glyphosate and its metabolite in biological
      fluids.
AB  - Glyphosate containing herbicides are an alternative to paraquat and are widely
      used throughout the world. Despite animal studies showing a low mammalian
      toxicity, human fatalities are reported after suicidal ingestions of glyphosate.
      Among the numerous analytical methods proposed, the reference method is the HPLC
      Monsanto procedure which is available in very few laboratories. The Monsanto
      procedure consists of a pre-column derivatization with detection of the resulting
      chromophore by HPLC with a variable wavelength UV/VIS detector. We propose a
      simple and rapid method for the diagnosis and monitoring of glyphosate poisoning.
      This method uses an aminoacid analyzer (Beckman 6300) with the program for
      biological fluids. With this procedure the glyphosate and amino methyl phosphoric
      acid retention times are respectively 1.75 and 3.54 min. This method gives a
      rapid result. The time between collecting the sample and completing the result is
      45 min. This method may be useful for the diagnosis and monitoring of glyphosate
      poisoning and is easy to perform with an apparatus usually available in every
      laboratory involved in aminoacid analysis.

PMID- 8523496
TI  - Coumaphos intoxications mimic food poisoning.
AB  - Reports of food poisoning caused by pesticide-contaminated food are rare in the
      medical literature. In this paper, we report six patients who suffered food
      poisoning in two separate episodes in which the pesticide coumaphos was
      apparently misused as a food flavoring. These six patients presented not only the
      general manifestations of gastroenteritis, but also some unusual extraintestinal
      symptoms. These included cholinergic overactivity (miosis, urinary incontinence
      and hypersalivation) that led us to suspect organophosphate intoxication. This
      diagnosis was confirmed by serial changes in RBC cholinesterase and
      pseudocholinesterase activity, and by the presence of coumaphos in the
      contaminated food. Of the six patients, one was dead on arrival. Another patient
      developed progressive respiratory failure and required mechanical ventilation.
      The mortality rate among our cases was 16.7%. Since the coumaphos was apparently
      added to food during cooking, its toxic effects do not appear to be mitigated by
      heating. When food poisoning cases present with both gastroenteritis and unusual
      autonomic symptoms, the autonomic syndromes will aid in the diagnosis and
      management of these critically ill patients.

PMID- 8523497
TI  - The relative efficacy of antidotes.
AB  - For many physicians an antidote is an antidote. According to the International
      Programme on Chemical Safety definition, an antidote is a therapeutic substance
      used to counteract the toxic action(s) of a specified xenobiotic. Given this wide
      definition, the efficacy of an antidote may vary considerably depending on which
      toxic action(s) being counteracted and the level of counteracting power. An
      almost 100% efficacy is seen using specific antagonists, such as naloxone in
      opiate poisoning or flumazenil in benzodiazepine poisoning, e.g. resulting in
      complete reversal of opiate toxicity unless complications, such as anoxic brain
      damage, have developed. At the other end of the efficacy scale, we may place
      chelating agents for heavy metal poisoning and diazepam for organophosphorus
      insecticide poisoning which are considered only to be an adjuncts to supportive
      care. When teaching clinical toxicology or recommending the use of antidotes in
      poisoned patients, the expected efficacy level of the antidote in question should
      be stressed. This may be particularly important in severe poisoning when the
      antidote may only be considered as an important adjunct to supportive care, e.g.
      deferoxamine in acute iron poisoning. Unless this is stressed, the unexperienced
      physician may rely too much on the antidote and pay insufficient attention to the
      supportive care. The varying efficacy levels will be discussed based on the
      presently ongoing International Programme on Chemical Safety/Commission of the
      European Communities evaluation program on antidotes.

PMID- 8523498
TI  - Outcome following organ removal from poisoned donors in brain death status: a
      report of 12 cases and review of the literature.
AB  - Experience with organ procurement from poisoned donors in brain death status is
      still limited in comparison with other etiologies. From 1963 to 1993, 2769 grafts
      (heart 141, kidney 1922, liver 623, pancreas 43) were performed in our University
      Hospital. Since 1975, among 1174 patients admitted to the ICU for acute
      poisoning, 12 patients who developed brain death status were considered for organ
      donation. The toxics involved were: methaqualone (1), benzodiazepines (1),
      benzodiazepines plus tricyclic antidepressants (2), barbiturates (2), insulin
      (2), carbon monoxide (1), cyanide (1), methanol (1), and acetaminophen (1).
      Exclusion criteria for organ removal were applied according to the nature of the
      toxin and the general criteria used for organ donation. The organs removed were:
      heart 5, heart valves for graft bank 2, kidneys 22, liver 4, pancreas 2,
      pancrease islet cells 2. Pertinent follow-up was obtained in 23 of 32 recipients.
      Immediate outcome was favorable in 20/23 patients (85%). Three patients died
      either from stroke, heart failure or preexisting encephalopathy. Two patients
      died from either chronic hepatic or renal graft rejection. None of these events
      could be directly related to a toxic origin. The one year survival rate of 75% is
      similar to that observed in the population who received organs from nonpoisoned
      donors. Organ procurement can be considered in few selected cases of acute
      poisoning. The accuracy of the diagnosis of irreversible brain damage is
      essential in this setting.

PMID- 8523499
TI  - Metobromuron/metolachlor ingestion with late onset methemoglobinemia in a
      pregnant woman successfully treated with methylene blue.
AB  - Metobromuron, a substituted urea herbicide, is widely used for control of grasses
      and broad-leaved weeds in Taiwan. Major systemic toxicity has not been reported
      following poisoning. A 22-year-old woman at 36 weeks of gestation was admitted to
      the emergency department three hours after ingestion of a mixture of 25%
      metobromuron and 25% metolachlor. Though stable initially, she developed central
      cyanosis 12 hours later. Emergent cesarean section was considered but
      administration of intravenous methylene blue readily reversed the cyanosis and
      prevented the operation. Recurrent cyanosis did not develop. Normal vaginal
      delivery occurred 17 days after the poisoning. Follow-up for four years revealed
      normal growth of the child. Metobromuron poisoning, like other urea herbicides,
      may cause methemoglobinemia via its hydrolysis products. Administration of
      methylene blue is effective treatment and should be considered in the treatment
      of methemoglobinemia following urea herbicide poisoning.

PMID- 8523500
TI  - Evaluation of urinary mercury excretion after administration of 2,3-dimercapto-1
      propane sulfonic acid to occupationally exposed men.
AB  - The purpose of this study was to determine the clinical efficacy of 2,3
      dimercapto-1-propane sulfonic acid, Na salt, on the urinary excretion of mercury
      as well as its possible adverse effects. Ten men with occupational mercury
      exposure (urinary level of 50 micrograms/g creatinine or more) were assigned to
      receive 2,3-dimercapto-1-propane sulfonic acid p.o. (DIMAVAL capsules, 100 mg)
      300 mg/d for five days. Informed written consent was obtained from each subject.
      Hematology analyses, blood, chemistry, and urinalysis were obtained at the start
      of the study, at the end of the 2,3-dimercapto-1-propane sulfonic acid treatment
      and 72 hours after the administration of the final dose of 2,3-dimercapto-1
      propane sulfonic acid. Twenty-four-hour urine mercury levels were closely
      monitored throughout therapy. All data and measurements before and during drug
      doses were evaluated by analyses of variance. In all subjects mean urine mercury
      was significantly increased (p < .05) after pre-2,3-dimercapto-1-propane sulfonic
      acid treatment. One subject had a moderate hypersensitivity reaction (rash) to
      2,3-dimercapto-1-propane sulfonic acid but no other toxic effects were observed.

PMID- 8523501
TI  - Antidotal efficacy of alpha-ketoglutaric acid and sodium thiosulfate in cyanide
      poisoning.
AB  - Alpha-ketoglutaric acid and sodium thiosulfate antagonize the toxic effects of
      cyanide. The present study was performed to test whether a synergistic effect may
      occur. The alpha-ketoglutaric acid/sodium thiosulfate solutions were injected
      intraperitoneally into mice prior to exposure to hydrogen cyanide (HCN) in a
      dynamic inhalation chamber or preceding an intraperitoneal injection of sodium
      cyanide (NaCN). All lethal concentration (LCT) and lethal dose (LD) values were
      determined after a period of 24 h. Alpha-ketoglutaric acid alone provided no
      protection at 250 mg/kg when challenged with HCN. Sodium thiosulfate 500 mg/kg
      provided a 5% protection. However, when these doses of alpha-ketoglutaric acid
      and sodium thiosulfate were combined, protection was increased by 18%. Alpha
      ketoglutaric acid (250 mg/kg) and sodium thiosulfate (1000 mg/kg) provided an
      additional 48% protection against a LCT88 of HCN. A single dose of alpha
      ketoglutaric acid (500 mg/kg) and sodium thiosulfate (1000 mg/kg) solutions
      afforded a 70% increase in survivability of the exposed animals. When mice were
      injected ip with 100 mg/kg of alpha-ketoglutaric acid 15 min prior to the
      injection of 5.5 mg/kg (LD50) of NaCN, the lethality was reduced to an LD30. Two
      hundred mg/kg alpha-ketoglutaric acid, challenged with the same dose of NaCN,
      reduced the lethality to 23%. When mice were challenged with 6.0 mg/kg of NaCN
      (LD70) pretreated with 100 mg/kg of alpha-ketoglutaric acid or 200 mg/kg of
      sodium thiosulfate, the LD was not altered in the former but reduced to an LD15
      in the latter. At higher doses of sodium thiosulfate (500 mg/kg), an LD60
      occurred at 13.6 mg/kg NaCN (2.5 x LD50).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523502
TI  - Intestinal infarction due to nifedipine overdose.
AB  - The first case of intestinal infarction associated with nifedipine overdose is
      presented. This is also the first reported case of an overdose with an extended
      release nifedipine preparation. The formation of a large gastric concretion of
      nifedipine tablets may have enhanced its local vasodilatory effects thereby
      producing mesenteric hypoperfusion, ischemia, and infarction.

PMID- 8523503
TI  - Thiazide diuretics induce cutaneous lupus-like adverse reaction.
AB  - One of the side effects reported in patients taking thiazide diuretics is
      photosensitivity. We report two patients who developed lupus-like skin lesions
      while taking thiazide diuretics. One patient developed erythematous scaling
      papules, patches and plaques on the upper extremities and trunk resembling
      subacute cutaneous lupus erythematosus. Histopathology of a skin biopsy from the
      trunk showed basal cell layer liquefaction and lichenoid interface changes
      suggestive of lupus erythematosus. The skin lesions resolved completely within
      two months of discontinuing thiazide therapy. The second patient developed
      multiple flesh colored urticarial plaques on the trunk one year after beginning
      thiazide therapy. Slight lichenoid interface changes were noted on a skin biopsy,
      along with dense mucin deposition in the papillary and deep dermis, suggestive of
      tumid lupus erythematosus. The skin lesions persisted despite discontinuing
      thiazide therapy, necessitating systemic corticosteroid treatment. Both patients
      had circulating anti-SSA/Ro autoantibodies and antinuclear antibodies. These two
      patients illustrate that thiazide diuretics may induce a cutaneous lupus
      erythematosus-like adverse reaction and production of anti-SSA/Ro autoantibodies
      as demonstrated by immunodiffusion, immunoblot and immunoprecipitation testing.

PMID- 8523504
TI  - The pathophysiology of airways disease.
AB  - More than 10 million airway branches exist in the normal human lung. Radiographic
      visualization is < 1% of this total. Many diseases affect the airways, each
      pathologic insult ultimately resulting in obstruction to airflow. Normally there
      is little resistance to airflow in the small airways (< 2 mm diameter); thus
      extensive disease may be present before it becomes clinically evident.
      Centrilobular emphysema is characterized by dilation and destruction of small
      airways, whereas bronchiolitis obliterans is characterized by concentric fibrous
      obliteration of small airways. High-resolution computed tomography, particularly
      comparison of images at full inspiration and full expiration, is the most
      sensitive radiographic method with which to image small airways disease.

PMID- 8523505
TI  - The bronchi: an imaging perspective.
AB  - Recent advances in high-resolution computed tomography (HRCT),
      inspiratory/expiratory CT staining of the lung, helical multiplanar
      reconstruction CT, and a broadened experience in magnetic resonance imaging of
      bronchial pathological conditions provide additional diagnostic information about
      the bronchi. This article reviews diffuse and focal lesions involving the large
      bronchi and small airways of the lung.

PMID- 8523506
TI  - Bronchiectasis.
AB  - Bronchiectasis is characterized by irreversible dilatation of the airways.
      Associated with a variety of underlying disorders, the common pathway for the
      development of bronchiectasis is chronic or recurrent infection. Bronchiectasis
      can occur in the normal host after a bout of severe infection or bronchial
      obstruction. Currently, it is more commonly seen in patients with abnormal host
      defenses including impaired clearance of secretions and disorders of cellular and
      humoral immunity. Historically, bronchography has been the imaging tool used for
      the evaluation of bronchiectasis. This procedure has been replaced by high
      resolution computed tomography, which is currently the modality of choice for
      imaging patients with bronchiectasis.

PMID- 8523507
TI  - Bronchiectasis in children.
AB  - Bronchiectasis (BR) is a descriptive term for abnormal, irreversibly dilated, and
      often thick walled bronchi, usually associated with inflammation. Causes are
      varied but include cystic fibrosis, aspiration, post infectious airway
      obstruction, immune abnormalities, immotile cilia, posttransplantation states,
      and congenital bronchial lesions. Although BR is uncommon in children, it causes
      significant mortality when present. Following a period of presumed decline due to
      antibiotics and vaccines, BR may increase in prevalence because of AIDS, organ
      transplantation complications, and changing patterns of childhood immunization.
      As with adults, high resolution CT (HRCT) is the most useful imaging tool for
      diagnosis and evaluation of bronchiectasis in children.

PMID- 8523508
TI  - Physiologic imaging of the lung with volumetric high-resolution CT.
AB  - The combination of high-resolution computed tomography (HRCT), rapid volumetric
      scanning, and advanced image display and analysis applications software is a
      powerful potential tool for the evaluation of physiologic and pharmacologic
      events in the lung. Currently employed in the experimental setting, this tool can
      provide verifiable and quantifiable information about regional responses in the
      lung, which were previously impossible to demonstrate. This is particularly true
      when physiologic or pharmacologic effects result in an anatomic change that can
      be directly imaged and measured within the limits of CT resolution. However,
      information about events occurring beyond resolution limits is potentially
      available indirectly from lung density and pulmonary blood flow measurements
      using CT techniques. The results of animal airway reactivity experiments making
      use of i.v. methacholine and CT imaging tools are presented as an example of
      "physiologic imaging."

PMID- 8523509
TI  - In vivo three-dimensional evaluation of the tracheobronchial tree.
AB  - Traditionally computed axial tomography has had limitations in evaluating
      diseases that affect the tracheobronchial tree because of respiratory-induced
      artifacts, with the likelihood of missing lesions as a result of misregistration.
      Spiral computed tomography (CT) differs from conventional CT in that the entire
      thorax can be rapidly imaged in the axial plane after a single breath-hold. Five
      patients underwent non-contrast-enhanced volumetric CT, with emphasis on three
      dimensional reconstruction, and endoscopic evaluation with pathologic
      confirmation. In all cases, there was complete corroboration between volumetric
      CT and endoscopic evaluation. The use of selective thresholds allowed the air
      within the tracheobronchial tree to be used as a negative contrast agent. Thus
      with the integration of selective windowing, detailed three-dimensional
      tracheobronchial anatomy may be elucidated. The absence of respiratory
      registration artifact due to the single breath-hold technique raises the
      confidence that three-dimensional and multiplanar images generated from such
      studies are accurate representations of the pathologic conditions at hand. By the
      integration of volumetric CT techniques and rapid three-dimensional display of
      tracheobronchial structures, volumetric CT bronchography becomes practical.

PMID- 8523510
TI  - CT mosaic pattern of lung attenuation: etiologies and terminology.
AB  - Areas of variable lung attenuation forming a "mosaic pattern" are occasionally
      seen on computed tomography (CT) or high-resolution CT (HRCT) images of the
      lungs. This CT mosaic pattern of lung attenuation is a nonspecific finding that
      can reflect the presence of vascular disease, airway abnormalities, or ground
      glass interstitial or air-space infiltrates. However, it is often possible to
      distinguish among these categories. In small airways disease and pulmonary
      vascular disease, the pulmonary vessels within the lucent regions of lung are
      small relative to the vessels in the more opaque lung. In infiltrative diseases,
      the vessels are more uniform in size throughout the different regions of lung
      attenuation. The distinction of small airways disease from primary vascular
      disease requires the use of paired inspiratory/expiratory CT scans. The terms
      "mosaic perfusion" or "mosaic oligemia" have also been used to describe this
      heterogeneous pattern of lung attenuation. We believe that the term "mosaic
      pattern of lung attenuation" is preferable when describing areas of variable lung
      attenuation because the term "mosaic perfusion" implies pulmonary vascular
      pathology.

PMID- 8523511
TI  - Evidence that the murine AIDS defective virus does not encode a superantigen.
AB  - The T-cell receptor repertoire was analyzed in C57BL/6 mice upon infection with
      helper-free stocks of the pathogenic murine AIDS (MAIDS) defective virus in order
      to demonstrate if, as previously reported, this virus encodes a superantigen. A
      polyclonal T-cell stimulation involving T cells expressing multiple V beta
      subsets occurred within the first week of infection, while late in the disease we
      could note only a 50% deletion of V beta 5 CD8+ cells. Transfection of the MAIDS
      virus genomic DNA into fibroblasts and B cells expressing major
      histocompatibility complex class II molecules failed to show any stimulation of
      cells expressing the specific V beta (V beta 5) previously reported to respond to
      MAIDS virus-infected cells. In addition, mice lacking V beta 5 cells did not show
      any significant decrease in susceptibility to the disease compared with mice
      expressing V beta 5 and bred on the same genetic background. Our in vivo and in
      vitro results fail to demonstrate a role for a superantigen encoded by the MAIDS
      defective viral genome in the pathogenesis of MAIDS.

PMID- 8523512
TI  - Regulation of human papillomavirus transcription by the differentiation-dependent
      epithelial factor Epoc-1/skn-1a.
AB  - Human papillomavirus (HPV) early gene expression is closely linked to the
      differentiation status of infected epithelial cells. Typically, HPV type 16
      (HPV16) or HPV18 E6 and E7 transcripts are only barely detectable within the
      undifferentiated basal cell layer, but their levels increase concomitantly with
      higher degrees of epithelial cell differentiation in suprabasal cells. A similar
      differentiation-dependent distribution of expression has been reported for the
      recently cloned epithelial cell specific transcription factor Epoc-1/skn-1a. We
      therefore examined whether Epoc-1/skn-1a may be directly involved in the
      activation of HPV E6/E7 transcription. Transient transfection studies showed that
      Epoc-1/skn-1a specifically stimulated the HPV16 and HPV18 E6/E7 promoters.
      Moreover, ectopically expressed Epoc-1/skn-1a was sufficient to stimulate HPV
      transcription also in nonepithelial cells. By deletion analyses, the Epoc-1/skn
      1a-responsive element was mapped to the promoter-proximal portion of the HPV18
      transcriptional control region. Footprint analyses and gel retardation assays
      demonstrated direct binding of Epoc-1/skn-1a to a hitherto uncharacterized site
      within this region. Mutation of the Epoc-1/skn-1a recognition site within the
      context of the complete HPV18 upstream regulatory region inhibited Epoc-1/skn-1a
      mediated transactivation. These results show that Epoc-1/skn-1a can directly
      activate the E6/E7 promoter by binding to the viral transcriptional control
      region. Thus, Epoc-1/skn-1a may be involved in the differentiation-dependent
      regulation of HPV transcription.

PMID- 8523513
TI  - Viral replication is required for induction of ocular immunopathology by herpes
      simplex virus.
AB  - Corneal infection of BALB/c mice with herpes simplex virus type 1 results in a
      chronic inflammatory response in the stroma termed herpetic stromal keratitis
      (HSK). This disease is considered to be immunopathological and mediated primarily
      by CD4+ T cells of the type 1 cytokine profile. However, the nature of the
      antigens, virus or host derived, which drive the inflammatory response remains in
      doubt. In this study, the relevance of infection with replicating virus for the
      subsequent development of HSK was evaluated with immunocompetent mice as well as
      with SCID mice reconstituted with herpes simplex virus-immune CD4+ T cells. In
      the corneas of immunocompetent mice, infectious virus, viral antigen, and mRNA
      expression were detectable for only a brief period of time (< or = 7 days
      postinfection), and all were undetectable by the time clinical lesions were
      evident (10 to 15 days). Viral replication, however, was necessary for the
      development of HSK in both models, since infection with UV-inactivated virus or
      with mutant viruses which were incapable of multiple rounds of replication in
      vivo failed to induce HSK. The inactivated and mutant viral preparations did,
      however, stimulate T-cell immune responses in immunocompetent mice. The results
      are discussed in terms of possible involvement of host antigens exposed in
      response to transient progeny virion replication in the immune-privileged cornea.

PMID- 8523515
TI  - E2 represses the late gene promoter of human papillomavirus type 8 at high
      concentrations by interfering with cellular factors.
AB  - The late gene promoter P7535 of the epidermodysplasia verruciformis-associated
      human papillomavirus type 8 (HPV8) is regulated by the viral E2 protein.
      Transfection experiments performed with the human skin keratinocyte cell line
      RTS3b and P7535 reporter plasmids revealed transactivation at low amounts and a
      repression of basal promoter activity at high amounts of E2 expression vector.
      This repression was promoter specific and correlated with the amount of
      transiently expressed E2 protein. Mutational analyses revealed that the negative
      regulation of P7535 activity is mediated by the low-affinity E2 binding site P2,
      which is separated by one nucleotide from the P7535 TATA box. Biochemical and
      genetic analyses suggested that repression is due to a displacement of the TATA
      box binding protein by E2 and an interference of E2 with promoter-activating
      cellular factors that specifically recognize the P2 sequence. The high
      conservation of the P2 sequence among several papillomaviruses (epidermodysplasia
      verruciformis-associated HPVs, HPV1, cottontail rabbit papillomavirus, and bovine
      papillomavirus type 1) in the vicinity of the late gene promoter cap site
      suggests that an interplay of E2 and cellular factors at this sequence element is
      important for the expression of structural proteins.

PMID- 8523514
TI  - The herpes simplex virus type 1 regulatory protein ICP27 coimmunoprecipitates
      with anti-Sm antiserum, and the C terminus appears to be required for this
      interaction.
AB  - The herpes simplex virus type 1 (HSV-1) immediate-early regulatory protein ICP27
      is required for the inhibition of host cell splicing during viral infection and
      for the reorganization of antigens associated with the small nuclear
      ribonucleoprotein particles (snRNPs). To determine what effect ICP27 had on
      splicing proteins that might cause their redistribution, we looked at proteins
      that were immunoprecipitated with anti-Sm antisera. No significant changes were
      seen in the migration or amounts of several snRNP common and snRNP-specific
      proteins from infected cells labeled with [35S]methionine, suggesting that the
      synthesis of these proteins was not altered by viral infection. However, when
      cells were labeled with 32Pi, differences were seen in the phosphorylation of at
      least two proteins depending on whether ICP27 was expressed. One protein, which
      had an apparent molecular mass of about 85 kDa, was highly phosphorylated during
      wild-type HSV-1 infection but much less so during infection with an ICP27 null
      mutant. The other protein, which migrated at the position of the U1 70-kDa
      protein and was precipitated with U1-specific antiserum, was also more highly
      phosphorylated when ICP27 was expressed during infection. Furthermore, a
      phosphoprotein with an apparent molecular mass of 63 kDa was found to
      coimmunoprecipitate with anti-Sm antisera during wild-type HSV-1 infection. ICP27
      has an apparent molecular mass of 63 kDa, and immunoblot analysis confirmed that
      ICP27 coimmunoprecipitated with snRNPs. Analysis of mutations throughout the
      ICP27 protein demonstrated that the region that was required for this interaction
      was the C terminus of the protein, which includes a cysteine-histidine-rich
      region that resembles a zinc-finger-like motif. These data suggest that ICP27
      interacts with snRNPs during infection and that it fosters changes in the
      phosphorylation state of at least two proteins that immunoprecipitate with
      snRNPs, although these studies do not demonstrate whether it does so directly or
      indirectly.

PMID- 8523516
TI  - Identification of the sequence on NS4A required for enhanced cleavage of the
      NS5A/5B site by hepatitis C virus NS3 protease.
AB  - In addition to NS3 protease, the NS4A protein is required for efficient cleavage
      of the nonstructural protein region of the hepatitis C virus polyprotein. To
      investigate the function and the sequence of NS4A required for the enhancement of
      NS3 protease activity, we developed an in vitro NS3 protease assay system
      consisting of three purified viral elements: (i) a recombinant NS3 protease which
      was expressed in Escherichia coli as a maltose-binding protein-NS3 fusion protein
      (MBP-NS3), (ii) synthetic NS4A fragments, and (iii) a synthetic peptide substrate
      which mimics the NS5A/5B junction. We showed that the NS3 protease activity of
      MBP-NS3 was enhanced in a dose-dependent manner by 4A18-40, which is a peptide
      composed of amino acid residues 18 to 40 of NS4A. The optimal activity was
      observed at a 10-fold molar excess of 4A18-40 over MBP-NS3. The coefficient for
      proteolytic efficiency, kcat/Km, of NS3 protease was increased by about 40 times
      by the addition of a 10-fold molar excess of 4A18-40. Using a series of
      truncations of 4A18-40, we estimated that amino acid residues 22 to 31 in NS4A
      (SVVIVGRIIL) constituted the core sequence for the effector activity. Single
      substitution experiments with 4A21-34, a peptide composed of amino acid residues
      21 to 34 of NS4A, suggested the importance of several residues (Val-23, Ile-25,
      Gly-27, Arg-28, Ile-29, and Leu-31) for its activity. In addition, we found that
      some single-amino-acid substitutions in 4A21-34 were able to inhibit the
      enhancement of NS3 protease activity by 4A18-40. This approach has potential as a
      novel strategy for inhibiting the NS3 protease activity important for hepatitis C
      virus proliferation.

PMID- 8523517
TI  - Intracellular retention of surface protein by a hepatitis B virus mutant that
      releases virion particles.
AB  - In the course of chronic infection, hepatitis B virus mutants can sometimes be
      found circulating in the serum as the predominant species. One class of such
      mutants contains in-frame deletions in the S promoter region. By transfecting
      hepatoma cells with wild-type or mutant viral genomic DNA, we have shown that one
      such mutant gives rise to extremely small amounts of S transcripts, as expected,
      and therefore expresses very little of the middle and small surface (viral
      envelope) proteins that are translated from these transcripts. In addition, this
      mutant gives rise to greater-than-wild-type levels of the preS1 transcripts,
      which are translated into the large surface protein. Because the large surface
      protein, unlike the other forms of surface protein, is incompetent for secretion,
      cells transfected with the mutant viral DNA contain large amounts of 20-nm
      particles within dilated perinuclear vesicles. Therefore, this and similar S
      promoter mutants may be one contributing factor in the pathogenesis of ground
      glass cells, which are hepatocytes containing nonsecretable viral surface
      proteins within dilated vesicles and are commonly found during chronic hepatitis
      B. Interestingly, DNA-containing virion particles are secreted into the medium by
      cells transfected with the mutant DNA, in amounts that are slightly larger than
      those secreted from wild-type-transfected cells, apparently because the amount of
      large surface protein is insufficient to block virion secretion. This finding may
      explain how such mutants can become the predominant circulating species in the
      serum, especially if there are selection pressures against the wild-type virus.

PMID- 8523518
TI  - Identification of two epitopes on the dengue 4 virus capsid protein recognized by
      a serotype-specific and a panel of serotype-cross-reactive human CD4+ cytotoxic T
      lymphocyte clones.
AB  - We analyzed the CD4+ T-lymphocyte response of a donor who had received an
      experimental live-attenuated dengue 4 virus (D4V) vaccine. Bulk culture
      proliferative responses of peripheral blood mononuclear cells (PBMC) to
      noninfectious dengue virus (DV) antigens showed the highest proliferation to D4V
      antigen, with lesser, cross-reactive proliferation to D2V antigen. We established
      CD4+ cytotoxic T-lymphocyte clones (CTL) by stimulation with D4 antigen. Using
      recombinant baculovirus antigens, we identified seven CTL clones that recognized
      D4V capsid protein. Six of these CTL clones were cross-reactive between D2 and
      D4, and one clone was specific for D4. Using synthetic peptides, we found that
      the D4V-specific CTL clone recognized an epitope between amino acids (aa) 47 and
      55 of the capsid protein, while the cross-reactive CTL clones each recognized
      epitopes in a separate location, between aa 83 and 92, which is conserved between
      D2V and D4V. This region of the capsid protein induced a variety of CD4+ T-cell
      responses, as indicated by the fact that six clones which recognized a peptide
      spanning this region showed heterogeneity in their recognition of truncations of
      this same peptide. The bulk culture response of the donor's PBMC to the epitope
      peptide spanning aa 84 to 92 was also examined. Peptides containing this epitope
      induced proliferation of the donor's PBMC in bulk culture, but peptides not
      containing the entire epitope did not induce proliferation. Also, PBMC stimulated
      in bulk culture with noninfectious D4V antigen lysed autologous target cells
      pulsed with peptides containing aa 84 to 92. These results indicate that this
      donor exhibits memory CD4+ T-cell responses directed against the DV capsid
      protein and suggest that the response to the capsid protein is dominant not only
      in vitro at the clonal level but in bulk culture responses as well. Since
      previous studies have indicated that the CTL responses to DV infection seem to be
      directed mainly against the envelope (E) and NS3 proteins, these results are the
      first to indicate that the DV capsid protein is also a target of the antiviral T
      cell response.

PMID- 8523519
TI  - A DNA structure is required for geminivirus replication origin function.
AB  - The genome of the geminivirus tomato golden mosaic virus (TGMV) consists of two
      single-stranded circular DNAs, A and B, that replicate through a rolling-circle
      mechanism in nuclei of infected plant cells. The TGMV origin of replication is
      located in a conserved 5' intergenic region and includes at least two functional
      elements: the origin recognition site of the essential viral replication protein,
      AL1, and a sequence motif with the potential to form a hairpin or cruciform
      structure. To address the role of the hairpin motif during TGMV replication, we
      constructed a series of B-component mutants that resolved sequence changes from
      structural alterations of the motif. Only those mutant B DNAs that retained the
      capacity to form the hairpin structure replicated to wild-type levels in tobacco
      protoplasts when the viral replication proteins were provided in trans from a
      plant expression cassette. In contrast, the same B DNAs replicated to
      significantly lower levels in transient assays that included replicating, wild
      type TGMV A DNA. These data established that the hairpin structure is essential
      for TGMV replication, whereas its sequence affects the efficiency of replication.
      We also showed that TGMV AL1 functions as a site-specific endonuclease in vitro
      and mapped the cleavage site to the loop of the hairpin. In vitro cleavage
      analysis of two TGMV B mutants with different replication phenotypes indicated
      that there is a correlation between the two assays for origin activity. These
      results suggest that the in vivo replication results may reflect structural and
      sequence requirements for DNA cleavage during initiation of rolling-circle
      replication.

PMID- 8523520
TI  - A conserved LXXLF sequence is the major determinant in p6gag required for the
      incorporation of human immunodeficiency virus type 1 Vpr.
AB  - The vpr gene product of human immunodeficiency virus type (HIV-1) is a virion
      associated regulatory protein. A transferable virion association motif for Vpr is
      located in the p6 domain of the HIV-1 Gag polyprotein. To map the sequences in p6
      that are involved in Vpr incorporation, we analyzed the ability of mutant forms
      of p6 to direct the incorporation of Vpr into chimeric viral particles. Our
      results show that the determinants which govern Vpr incorporation are largely
      confined to a C-terminal region of the p6 domain. Within this region, three
      hydrophobic residues in a highly conserved sequence motif (L-X-S-L-F-G) are
      absolutely required. Remarkably, the transfer of the conserved motif and of a
      single flanking residue to a heterologous Gag polyprotein was sufficient to
      transfer the ability to incorporate Vpr at moderate levels. The transfer of
      residues 32 to 46 of p6 led to Vpr incorporation levels that were comparable to
      those obtained with full-length HIV-1 Gag protein, indicating that this region
      contains essentially all the information required for efficient Vpr
      incorporation.

PMID- 8523521
TI  - Gene expression and cytopathic effect of vaccinia virus inactivated by psoralen
      and long-wave UV light.
AB  - Induction of the cytopathic effect (CPE) in cells infected with poxvirus seems
      ubiquitous in that it has been associated with all different strains and
      preparations of poxviruses, regardless of the replicating status of these
      viruses. The study of the mechanisms by which CPE is induced by nonreplicating
      poxviruses is hampered by the lack of any noncytopathic mutant strains and
      preparations. In this paper, we report on the patterns of gene expression and
      induction of CPE by vaccinia viruses treated by limited cross-linking with
      psoralen and long-wave UV light (PLWUV). We show that treatment of cell-free
      virus with PLWUV could inactivate viral replication without abolishing the
      ability of the virus to infect cells. Viral transcription as indicated by
      reporter genes was generally enhanced and prolonged under early viral promoters
      and abolished under late promoters. Furthermore, increasing the levels of cross
      linking with PLWUV resulted in a decrease and abolishment of viral expression of
      a large reporter gene and a concomitant loss of the induction of CPE. Cells
      infected with such a virus were able to express the reporter genes and
      proliferate. The generation of nonreplicating and noncytopathic recombinant
      vaccinia viruses may help in studies of the mechanisms of CPE induction by
      poxvirus and may facilitate the use of poxviral vectors in broader areas of
      research and clinical applications.

PMID- 8523522
TI  - Selective response of gamma delta T-cell hybridomas to orthomyxovirus-infected
      cells.
AB  - A gamma delta T-cell hybridoma established from influenza virus-infected mice
      responded to a reproducible way when cultured with influenza virus-infected
      stimulators. Subclones of this line responded to cells infected with influenza
      viruses A/PR/8/34 (H1N1), X-31 (H3N2), and B/HK/8/73 but not to cells infected
      with vaccinia virus or Sendai virus. This spectrum of response to both type A and
      type B orthomyxoviruses has never been recognized for the alpha beta T-cell
      receptor-positive subsets. There was no response to cells infected with a panel
      of recombinant vaccinia viruses expressing all individual influenza virus
      proteins, and so it is unlikely that the stimulating antigen is of viral origin.
      The alternative is that the antigen is a cellular molecule induced in influenza
      virus-infected cells. Infectious virus was required for stimulation, and
      immunofluorescence studies showed increased expression of heat shock protein 60
      (Hsp60) in influenza virus- but not Sendai virus- or vaccinia virus-infected
      cells. Both the hybridoma generated from influenza virus-infected mice and an
      established hybridoma which uses the same gamma delta T-cell receptor combination
      responded to recombinant Hsp60. Furthermore, the Hsp60-reactive hybridoma, which
      was obtained from an uninfected mouse, also responded to influenza virus-infected
      cells, indicating that Hsp60 may indeed be the target antigen.

PMID- 8523523
TI  - The promoter and transcriptional unit of a novel herpes simplex virus 1 alpha
      gene are contained in, and encode a protein in frame with, the open reading frame
      of the alpha 22 gene.
AB  - The herpes simplex virus type 1 genome encodes a set of genes (alpha genes)
      expressed in the absence of de novo viral protein synthesis. Earlier studies have
      shown that the product of the alpha 22 gene, a member of this set, is
      nucleotidylylated by casein kinase II and phosphorylated by viral protein kinases
      encoded by UL13 and US3. Mutants lacking the carboxyl-terminal domain starting
      with amino acid 200 exhibit reduced capacity to replicate in primary human cell
      strains or in cells of rodent derivation and also exhibit reduced expression of a
      subset of gamma or late genes. We report that the domain of the alpha 22 gene is
      transcribed by two 3'-coterminal mRNAs. The longer transcript reported encodes
      the 420-amino-acid alpha 22 protein, whereas the shorter transcript reported here
      encodes a protein containing the carboxyl-terminal 273 amino acids of the alpha
      22 protein. The shorter gene is designated US1.5. The US1.5 mRNA is synthesized
      in cells infected and maintained in the presence of cycloheximide and under other
      conditions which restrict viral gene expression to alpha genes. In-frame
      insertion of linkers encoding 18, 21, or 22 amino acids after codon 200 or 240 of
      the alpha 22 protein did not affect the known functions or phenotype associated
      with the wild-type alpha 22 gene or its product. Earlier studies have placed the
      nucleotidylylated sequences in the amino-terminal portion of the protein. The
      results of these studies indicate that the US1.5 gene encodes the functions
      associated with replication in human primary or rodent cells and optimal
      expression of alpha 0 and gamma genes. This finding brings the number of genes
      known to map in the unique short region of the herpes simplex virus type 1 DNA to
      14 and the total number of different genes to 78.

PMID- 8523524
TI  - RNA aptamers selected to bind human immunodeficiency virus type 1 Rev in vitro
      are Rev responsive in vivo.
AB  - RNA aptamers (binding sequences) that can interact tightly and specifically with
      the human immunodeficiency virus type 1 Rev protein have previously been selected
      from random sequence pools. Although the selected sequences compete with the wild
      type Rev-binding element (RBE) in vitro, it was not known whether they would be
      able to functionally replace the RBE in vivo. Two aptamers that were different
      from the wild-type RBE in terms of both primary sequence and secondary structure
      were inserted into the full-length Rev-responsive element (RRE) in place of the
      RBE. The hybrid RREs were assayed for their ability to mediate Rev function in
      vivo using a reporter system. The aptamers were found to be functionally
      equivalent to the wild-type element when the assay system was saturated with Rev
      and better than the wild-type element when Rev was limiting. These results
      demonstrate that the affinity of the primary Rev-binding element rather than its
      particular sequence may be most responsible for conferring Rev responsiveness on
      viral mRNAs. Moreover, the fact that increased binding ability can lead to
      increased Rev responsiveness suggests that cellular factors do not directly
      influence the Rev:RBE interaction. Finally, since sequences distinct from the RBE
      are found to be Rev responsive, it may be possible for the RBE to readily mutate
      in response to drugs or gene therapy reagents that target the Rev:RBE
      interaction.

PMID- 8523525
TI  - The promoter activity of long terminal repeats of the HERV-H family of human
      retrovirus-like elements is critically dependent on Sp1 family proteins
      interacting with a GC/GT box located immediately 3' to the TATA box.
AB  - The HERV-H family of endogenous retrovirus-like elements is widely distributed in
      the human genome, with about 1,000 full-length elements and a similar number of
      solitary long terminal repeats (LTRs). HERV-H LTRs have been shown to direct the
      transcription of both HERV-H-encoded and adjacent cellular genes. Transcripts of
      HERV-H elements are especially abundant in placenta, teratocarcinoma cell lines,
      and cell lines derived from testicular and lung tumors. Here we report that only
      a subset of HERV-H LTRs display promoter activity in human cell lines and that
      these LTRs are characterized by the presence of a GC/GT box immediately
      downstream of the TATA box. This GC/GT box is required for promoter activity,
      while, surprisingly, the TATA box is dispensable. The ubiquitously expressed
      transcription factors Sp1 and Sp3 bound to this GC/GT box and stimulated
      transcription from the promoter-active LTRs in the teratocarcinoma cell line
      NTera2-D1. However, in HeLa and Drosophila SL-2 cells, Sp1 acted as a
      transcriptional activator of the LTRs, while Sp3 acted as a repressor of Sp1
      mediated transcriptional activation. Cotransfection studies also revealed that
      the tissue-specific Sp1-related protein BTEB bound to this GC/GT box and
      stimulated transcription from the LTR promoters in NTera2-D1 cells. These results
      show that members of the Sp1 protein family are crucial determinants for
      transcriptional activation of HERV-H LTR promoters and suggest that these
      proteins may also be involved in determining the tissue-specific expression
      pattern of HERV-H elements.

PMID- 8523526
TI  - Upregulation of Fas ligand expression by human immunodeficiency virus in human
      macrophages mediates apoptosis of uninfected T lymphocytes.
AB  - Apoptosis has been proposed to mediate CD4+ T-cell depletion in human
      immunodeficiency virus (HIV)-infected individuals. Interaction of Fas ligand
      (FasL) with Fas (CD95) results in lymphocyte apoptosis, and increased
      susceptibility to Fas-mediated apoptosis has been demonstrated in lymphocytes
      from HIV-infected individuals. Cells undergoing apoptosis in lymph nodes from HIV
      infected individuals do not harbor virus, and therefore a bystander effect has
      been postulated to mediate apoptosis of uninfected cells. These data raise the
      possibility that antigen-presenting cells are a source of FasL and that HIV
      infection of cells such as macrophages may induce or increase FasL expression. In
      this report, we demonstrate that HIV infection of monocytic cells not only
      increases the surface expression of Fas but also results in the de novo
      expression of FasL. Interference with the FasL-Fas interaction by anti-Fas
      blocking antibodies abrogates HIV-induced apoptosis of monocytic cells. Human
      monocyte-derived macrophages from healthy donors contain detectable FasL mRNA,
      which is further upregulated following HIV infection with monocytotropic strains.
      HIV-infected human macrophages result in the apoptotic death of Jurkat T cells
      and peripheral blood T lymphocytes. Interruption of the FasL-Fas interaction
      abrogates the HIV-infected macrophage-dependent death of T lymphocytes. These
      results provide evidence that human macrophages can provide a source of FasL,
      especially following HIV infection, and can thus participate in lymphocyte
      depletion in HIV-infected individuals.

PMID- 8523527
TI  - Expression in animal cells and characterization of the hepatitis E virus
      structural proteins.
AB  - Hepatitis E virus (HEV) is a major human pathogen in much of the developing
      world. It is a positive-strand RNA virus with a 7.5-kb polyadenylated genome
      consisting of three open reading frames (ORFs). In the absence of an in vitro
      culture system, the replication and expression strategy of HEV and the nature of
      its encoded polypeptides are not well understood. We have expressed the two ORFs
      constituting the structural portion of the HEV genome in COS-1 cells by using
      simian virus 40-based expression vectors and in vitro by using a coupled
      transcription-translation system. We show here that the major capsid protein,
      encoded by ORF2, is an 88-kDa glycoprotein which is expressed intracellularly as
      well as on the cell surface and has the potential to form noncovalent homodimers.
      It is synthesized as a precursor (ppORF2) which is processed through signal
      sequence cleavage into the mature protein (pORF2), which is then glycosylated
      (gpORF2). The minor protein, pORF3, encoded by ORF3 is a 13.5-kDa nonglycosylated
      protein expressed intracellularly and does not show any major processing. pORF3
      interacts with a cellular protein of about 18 kDa which we call 3IP, the pORF3
      interacting protein. The significance of these findings are discussed in light of
      an existing model of HEV genome replication and expression.

PMID- 8523528
TI  - Foamy virus vectors.
AB  - Human foamy virus (HFV) is a retrovirus of the spumavirus family. We have
      constructed vectors based on HFV that encode neomycin phosphotransferase and
      alkaline phosphatase. These vectors are able to transduce a wide variety of
      vertebrate cells by integration of the vector genome. Unlike vectors based on
      murine leukemia virus, HFV vectors are not inactivated by human serum, and they
      transduce stationary-phase cultures more efficiently than murine leukemia virus
      vectors. These properties, as well as their large packaging capacity, make HFV
      vectors promising gene transfer vehicles.

PMID- 8523529
TI  - Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency
      virus-infected monocytes.
AB  - The molecular mechanisms regulating human immunodeficiency virus (HIV)
      persistence in a major cell reservoir such as the macrophage remain unknown. NF
      kappa B is a transcription factor involved in the regulation of the HIV long
      terminal repeat and is selectively activated following HIV infection of human
      macrophages. Although little information as to what signal transduction pathways
      mediate NF-kappa B activation in monocytes-macrophages is available, our previous
      work indicated that classical protein kinase C (PKC) isoenzymes were not involved
      in the HIV-mediated NF-kappa B activation. In this study, we have focused on
      atypical PKC isoenzymes. PKC-zeta belongs to this family and is known to be an
      important step in NF-kappa B activation in other cell systems. Immunoblotting
      experiments with U937 cells demonstrate that PKC-zeta is present in these cells,
      and its expression can be downmodulated by antisense oligonucleotides (AO). The
      HIV-mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta. In
      addition, cotransfection of a negative dominant molecule of PKC-zeta (PKC-zeta
      mut) with NF-kappa B-dependent reporter genes selectively inhibits the HIV- but
      not phorbol myristate acetate- or lipopolysaccharide-mediated activation of NF
      kappa B. That PKC-zeta is specific in regulating NF-kappa B is concluded from the
      inability of PKC-zeta(mut) to interfere with the basal or phorbol myristate
      acetate-inducible CREB- or AP1-dependent transcriptional activity. Lastly, we
      demonstrate a selective inhibition of p24 production by HIV-infected human
      macrophages when treated with AO to PKC-zeta. Altogether, these results suggest
      that atypical PKC isoenzymes, including PKC-zeta, participate in the signal
      transduction pathways by which HIV infection results in the activation of NF
      kappa B in human monocytic cells and macrophages.

PMID- 8523530
TI  - Amino acids critical for the functions of the bovine papillomavirus type 1 E2
      transactivator.
AB  - The N-terminal domain of the bovine papillomavirus type 1 E2 protein is important
      for viral DNA replication, for transcriptional transactivation, and for
      interaction with the E1 protein. To determine which residues of this 200-amino
      acid domain are important for these activities, single conservative amino acid
      substitutions have been generated in 17 residues that are invariant among all
      papillomavirus E2 proteins. The resulting mutated E2 proteins were tested for the
      ability to support viral DNA replication, activate transcription, and
      cooperatively bind to the origin of replication with the E1 protein. We
      identified five mutated proteins that were completely defective for
      transcriptional activation and either were defective or could support viral DNA
      replication at only low levels. However, several of these proteins could still
      interact efficiently with the E1 protein. In addition, we identified several
      mutated proteins that were unable to efficiently cooperatively bind to the origin
      with the E1 protein. Although a number of the mutated proteins demonstrated wild
      type activity in all of the functions tested, only 3 out of 17 mutated viral
      genomes were able to induce foci in a C127 focus formation assay when the
      mutations were generated in the background of the entire bovine papillomavirus
      type 1 genome. This finding suggests that the E2 protein may have additional
      activities that are important for the viral life cycle.

PMID- 8523531
TI  - Use of recombinant protein to identify a motif-negative human cytotoxic T-cell
      epitope presented by HLA-A2 in the hepatitis C virus NS3 region.
AB  - To define cytotoxic T-cell (CTL) epitopes, the common approach involving the use
      of a series of overlapping synthetic peptides covering the whole protein sequence
      is impractical for large proteins. Motifs identify only a fraction of epitopes.
      To identify human CTL epitopes in the NS3 region of hepatitis C virus (HCV), we
      modified an approach using recombinant protein and the ability of short peptides
      to bind to class I major histocompatibility complex (MHC) molecules. Peripheral
      blood mononuclear cells from an HCV-infected patient were stimulated with a
      proteolytic digest of the recombinant NS3 protein to expand CTL to any active
      peptides in the digest. The digest was fractionated by reverse-phase high
      performance liquid chromatography, and fractions were assessed for the ability to
      sensitize targets for lysis by CTL. The most active fraction was sequenced,
      identifying a 15-residue peptide (NS3-1J; TITTGAPVTYSTYGK). This sequence was
      confirmed to be the source of the activity by synthesis of the corresponding
      peptide. CTL lines specific for NS3-1J were established from two HCV-infected
      patients (both HLA-A2 and -B7 positive) by stimulation with the synthetic peptide
      in vitro. The CTL were HLA-A2 restricted, and the minimal epitope was mapped to a
      decapeptide NS3-1J (10.4). As this minimal epitope lacks the common HLA-A2
      binding motif, this technique is useful for mapping CTL epitopes independent of
      known motifs and without the requirement for enormous numbers of overlapping
      peptides. Because this peptide is presented by the most common HLA class I
      molecule, present in almost half the population, it might be a useful component
      of a vaccine against HCV.

PMID- 8523532
TI  - Mechanism for inhibition of influenza virus RNA polymerase activity by matrix
      protein.
AB  - Influenza virus M1 protein has been shown to inhibit the transcription catalyzed
      by viral ribonucleoprotein complexes isolated from virions. Here, this inhibition
      mechanism was studied with the recombinant M1 protein purified from Escherichia
      coli expressing it from cDNA. RNA mobility shift assays indicated that both
      soluble and aggregate forms of the recombinant M1, which were separated by the
      glycerol density gradient, were bound to RNA. Once an M1-RNA complex was formed,
      free M1 was bound to the M1-RNA complex cooperatively rather than to free RNA. In
      addition, the recombinant M1 was capable of binding to preformed RNA-nucleocapsid
      protein complexes. The mechanism for inhibition of the viral RNA polymerase
      activity was analyzed by the in vitro RNA synthesis systems that depend on an
      exogenously added RNA template. These systems were more sensitive for evaluating
      the inhibition by M1 than the RNA synthesis system depending on an endogenous RNA
      template. The RNA synthesis inhibition was examined at four steps: cleavage of
      capped RNA; incorporation of the first nucleotide, GMP; limited elongation; and
      synthesis of full-size product. M1 inhibited RNA synthesis mainly at the early
      steps. The experiments with M1 mutant proteins containing amino acid deletions
      suggested that the M1 region between amino acid residues 91 and 111 was essential
      for anti-RNA synthesis activity, RNA binding, and oligomerization of M1 on RNA.

PMID- 8523533
TI  - Analysis of the cell fusion activities of chimeric simian immunodeficiency virus
      murine leukemia virus envelope proteins: inhibitory effects of the R peptide.
AB  - It was previously reported that truncation or proteolytic removal of the C
      terminal 16 amino acids (the R peptide) from the cytoplasmic tail of the murine
      leukemia virus (MuLV) envelope protein greatly increases its fusion activity. In
      this study, to investigate the specificity of the effect of the R peptide on the
      fusion activity of viral envelope proteins, we expressed simian immunodeficiency
      virus (SIV)-MuLV chimeric proteins in which the entire cytoplasmic tail of the
      SIV envelope protein was replaced by either the full-length MuLV cytoplasmic tail
      or a truncated MuLV cytoplasmic tail with the R peptide deleted. Extensive fusion
      of CD4-positive cells with the chimeric protein containing a truncated MuLV
      cytoplasmic tail was observed. In contrast, no cell fusion activity was found for
      the chimeric protein with a full-length MuLV cytoplasmic tail. We constructed
      another SIV-MuLV chimeric protein in which the MuLV R peptide was added to an SIV
      envelope protein cytoplasmic tail 17 amino acids from its membrane-spanning
      domain. No fusion activity was observed within this construct, while the
      corresponding truncated SIV envelope protein lacking the R peptide showed
      extensive fusion activity. No significant difference in the transport or surface
      expression was observed among the various SIV-MuLV chimeric proteins and the
      truncated SIV envelope protein. Our results thus demonstrate that the MuLV R
      peptide has profound inhibitory effects on virus-induced cell fusion, not only
      with MuLV but also in a distantly related retroviral envelope protein which
      utilizes a different receptor and fuses different cell types.

PMID- 8523534
TI  - Receptor (CD46) modulation and complement-mediated lysis of uninfected cells
      after contact with measles virus-infected cells.
AB  - Recently, it has been observed that the infection of human target cells with
      certain measles virus (MV) strains leads to the downregulation of the major MV
      receptor CD46. Here we report that CD46 downregulation can be rapidly induced in
      uninfected cells after surface contact with MV particles or MV-infected cells.
      Receptor modulation is detectable after 30 min of cocultivation of uninfected
      cells with MV-infected cells and is complete after 2 to 4 h, a time after which
      newly synthesized MV hemagglutinin (MV-H) cannot be detected in freshly infected
      target cells. This contact-mediated receptor modulation is also induced by
      recombinant MV-H expressed by vaccinia virus and is inhibitable with antibodies
      against CD46 and MV-H. By titrating the effect with MV Edmonston strain-infected
      cells, a significant contact-mediated CD46 modulation was detectable up to a
      ratio of 1 infected to 64 uninfected cells. As a result of CD46 downregulation,
      an increased susceptibility of uninfected cells for complement-mediated lysis was
      observed. This phenomenon, however, is MV strain dependent, as observed for the
      downregulation of CD46 after MV infection. These data suggest that in acute
      measles or following measles vaccination, uninfected cells might also be
      destroyed by complement after contacting an MV-infected cell.

PMID- 8523535
TI  - Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus
      type 1 corneal infection.
AB  - Following herpes simplex virus type 1 (HSV-1) infection of the cornea, the virus
      is transmitted to the trigeminal ganglion, where a brief period of virus
      replication is followed by establishment of a latent infection in neurons. A
      possible role of the immune system in regulating virus replication and
      maintaining latency in the sensory neurons has been suggested. We have
      investigated the phenotype and cytokine pattern of cells that infiltrate the A/J
      mouse trigeminal ganglion at various times after HSV-1 corneal infection. HSV
      antigen expression in the trigeminal ganglion (indicative of the viral lytic
      cycle) increased until day 3 postinfection (p.i.) and then diminished to
      undetectable levels by day 7 p.i. The period of declining HSV antigen expression.
      was associated with a marked increase in Mac-1+ cells. These cells did not appear
      to coexpress the F4/80+ (macrophage) or the CD8+ (T cell) markers, and none
      showed polymorphonuclear leukocyte morphology, suggesting a possible early
      infiltration of natural killer cells. There was also a significant increase in
      the trigeminal ganglion of cells expressing the gamma delta T-cell receptor, and
      these cells were found almost exclusively in very close association with neurons.
      This period was also characterized by a rapid and equivalent increase in cells
      expressing gamma interferon and interleukin-4. The density of the inflammatory
      infiltrate in the trigeminal ganglion increased until days 12 to 21 p.i., when it
      was predominated by CD8+, Mac-1+, and tumor necrosis factor-expressing cells,
      which surrounded many neurons. By day 92 p.i., the inflammatory infiltrate
      diminished but was heaviest in mice with active periocular skin disease. Our data
      are consistent with the notion that gamma interferon produced by natural killer
      cells and/or gamma delta T cells may play an important role in limiting HSV-1
      replication in the trigeminal ganglion during the acute stage of infection. In
      addition, tumor necrosis factor produced by CD8+ T cells and macrophages may
      function to maintain the virus in a latent state.

PMID- 8523536
TI  - Vaccinia virus glycoprotein A34R is required for infectivity of extracellular
      enveloped virus.
AB  - The vaccinia virus strain Western Reserve (WR) A34R gene encodes a C-type lectin
      like glycoprotein, gp22-24, that is present in the outer membrane of
      extracellular enveloped virus (EEV) with type II membrane topology (S.A. Duncan
      and G.L. Smith, J. Virol. 66:1610-1621, 1992). Here we that a WR A34R deletion
      mutant (WR delta A34R) released 19- to 24-fold more EEV from infected cells than
      did WR virus, but the specific infectivity of the released virions was reduced 5-
      to 6-fold. Rupture of the WR delta A34R EEV outer envelope by freeze-thawing
      increased virus infectivity by five- to sixfold, because of the release of
      infectious intracellular mature virus. All other known EEV-specific proteins are
      incorporated into WR delta A34R EEV, and thus the loss of gp22-24 is solely
      responsible for the reduction of EEV specific infectivity. The WR delta A34R
      virus is highly attenuated in vivo compared with WR or a revertant virus in which
      the A34R gene was reinserted into WR delta A34R. This attenuation is consistent
      with the known important role of EEV in virus dissemination and virulence.
      Vaccinia virus strain International Health Department-J (IHD-J) produces large
      amounts of EEV and forms comets because of an amino acid substitution within the
      A34R protein (R. Blasco, R. Sisler, and B. Moss, J. Virol. 67:3319-3325, 1993),
      but despite this, IHD-J EEV has a specific infectivity equivalent to that of WR
      EEV. Substitution of the IHD-J A34R gene into the WR strain induced comet
      formation and greater release of EEV, while coexpression of both genes did not;
      hence, the WR phenotype is dominant. All orthopoxviruses tested express the A34R
      protein, but most viruses, including variola virus, have the WR rather than the
      IHD-J A34R genotype. The A34R protein affects plaque formation, EEV release, EEV
      infectivity, and virus virulence.

PMID- 8523537
TI  - The region of the herpes simplex virus type 1 LAT gene that is colinear with the
      ICP34.5 gene is not involved in spontaneous reactivation.
AB  - The goal of this report was to determine if the region of the LAT gene that is
      colinear with ICP34.5 (kb 6.2 to 7.1 of LAT) is involved in spontaneous
      reactivation of herpes simplex virus type 1. We inserted one copy of the ICP34.5
      gene into the unique long region of a herpes simplex virus type 1 (strain McKrae)
      mutant lacking both copies of ICP34.5 (one in each viral long repeat) and the
      corresponding 917-nucleotide colinear portion of LAT (kb 6.2 to 7.1). Rabbits
      were ocularly infected with this mutant, and spontaneous reactivation relative to
      that for the wild-type virus and the original mutant was measured. As we
      previously reported, the original ICP34.5-deleted virus (d34.5) was significantly
      impaired for spontaneous reactivation and virulence (G. C. Perng, R. L. Thompson,
      N. M. Sawtell, W. E. Taylor, S. M. Slanina, H. Ghiasi, R. Kaiwar, A. B. Nesburn,
      and S. L. Wechsler, J. Virol. 69:3033-3041, 1995). In contrast, we report here
      that restoration of one copy of ICP34.5 at a distant location completely restored
      the wild-type level of in vivo spontaneous reactivation, despite retention of the
      deletion in LAT (spontaneous reactivation rate = 0.3 to 1.4% for the ICP34.5
      deletion mutant, 7.7 to 19.6% for the wild type, and 9 to 16.1% for virus with
      one copy of ICP34.5). Thus, the 917-nucleotide region of LAT from kb 6.2 to 7.1
      was not involved in the LAT function required for wild-type spontaneous
      reactivation. We also found that restoration of a single ICP34.5 gene in a novel
      location did not restore wild-type virulence (rabbit death rate = 0% [0 of 15]
      for the original ICP34.5 deletion mutant, 8% [2 of 24] for the single-copy
      IPC34.5 virus, and 52% [14 of 27] for wild-type virus; P < 0.001 for one versus
      two copies of ICP34.5). It is likely that either two gene doses of ICP34.5 or its
      location in the long repeat is essential for full functionality of ICP34.5's
      virulence function. Furthermore, the ability of the single-copy ICP34.5 virus to
      reactivate at wild-type levels despite being significantly less virulent than
      wild-type virus separates the spontaneous reactivation phenotype from the
      virulence phenotype.

PMID- 8523538
TI  - Saccharomyces cerevisiae L-BC double-stranded RNA virus replicase recognizes the
      L-A positive-strand RNA 3' end.
AB  - L-A and L-BC are two double-stranded RNA viruses present in almost all strains of
      Saccharomyces cerevisiae. L-A, the major species, has been extensively
      characterized with in vitro systems established, but little is known about L-BC.
      Here we report in vitro template-dependent transcription, replication, and RNA
      recognition activities of L-BC. The L-BC replicase activity converts positive,
      single-stranded RNA to double-stranded RNA by synthesis of the complementary RNA
      strand. Although L-A and L-BC do not interact in vivo, in vitro L-BC virions can
      replicate the positive, single-stranded RNA of L-A and its satellite, M1, with
      the same 3' end sequence and stem-loop requirements shown by L-A virions for its
      own template. However, the L-BC virions do not recognize the internal replication
      enhancer of the L-A positive strand. In a direct comparison of L-A and L-BC
      virions, each preferentially recognizes its own RNA for binding, replication, and
      transcription. These results suggest a close evolutionary relation of these two
      viruses, consistent with their RNA-dependent RNA polymerase sequence
      similarities.

PMID- 8523539
TI  - Lipid membrane fusion induced by the human immunodeficiency virus type 1 gp41 N
      terminal extremity is determined by its orientation in the lipid bilayer.
AB  - The amino-terminal extremity of the human immunodeficiency virus type 1
      transmembrane protein (gp41) is thought to play a pivotal role in the fusion of
      virus membranes with the plasma membrane of the target cell and in syncytium
      formation. Peptides with sequences taken from the human immunodeficiency virus
      type 1 gp41 fusogenic (synthetic peptides SPwt and SP-2) and nonfusogenic (SP-3
      and SP-4) glycoproteins adopt mainly a beta-sheet conformation in the absence of
      lipid, as determined by attenuated total reflection Fourier transform infrared
      spectroscopy, and after interaction with large unilamellar liposomes, the beta
      sheet is partly converted into an alpha-helical conformation. Peptides SPwt and
      SP-2 but not SP-3 or SP-4 were able to promote lipid mixing as assessed by
      fluorescence energy transfer assay and dye leakage in a vesicle leakage assay. By
      using polarized attenuated total reflection Fourier transform infrared
      spectroscopy, SPwt and SP-2 were found to adopt an oblique orientation in the
      lipid membrane whereas SP-3 and SP-4 were oriented nearly parallel to the plane
      of the membrane. These findings confirm the correlation between the membrane
      orientation of the alpha-helix and the lipid mixing ability in vitro.
      Interestingly, the data provide a direct correlation with the fusogenic activity
      of the parent glycoproteins in vivo.

PMID- 8523540
TI  - Pathogenesis of type II avian adenovirus infection in turkeys: in vivo immune
      cell tropism and tissue distribution of the virus.
AB  - Hemorrhagic enteritis virus (HEV), a type II avian adenovirus, causes intestinal
      hemorrhages and immunosuppression in turkeys. In this study, we exposed turkeys
      to virulent HEV and examined fractionated spleen cells for the presence of viral
      DNA by in situ hybridization and amplification of DNA extracted from virus
      infected cells by PCR. HEV replication was detected only in the immunoglobulin M
      bearing B lymphocytes and macrophage-like cells but not in the CD4+ or CD8+ T
      lymphocytes. The inability to infect T cells distinguishes type II avian
      adenoviruses from lymphotropic mammalian adenoviruses which infect and replicate
      in T cells. Furthermore, these data suggested that HEV-induced immunosuppression
      in turkeys may be due to the effect of the virus on B lymphocytes and
      macrophages. We also examined tissue tropism of HEV by in situ hybridization
      conducted on sections of lymphoid and nonlymphoid tissues. Large numbers of HEV
      positive cells were detected in spleen and cecal tonsils. Diminutive viral
      activity was present in the intestines, the principal site of HEV-induced
      pathology. Thus, intestinal pathology was not associated with local cytopathic
      viral replication. This result and our previous observation that cyclosporin A
      abrogated intestinal hemorrhaging in HEV-infected turkeys strongly suggested that
      intestinal lesion induced by this virus may be immune system mediated.

PMID- 8523541
TI  - Mouse adaptation determinants of poliovirus type 1 enhance viral uncoating.
AB  - Most poliovirus (PV) strains, such as PV type 1/Mahoney, cannot infect the mouse
      central nervous system. We previously identified two determinants of mouse
      adaptation of PV type 1/Mahoney at positions 22 and 31 of the viral capsid
      proteins VP1 and VP2, respectively (T. Couderc, J. Hogle, H. Le Blay, F. Horaud,
      and B. Blondel, J. Virol. 67:3808-3817, 1993). These residues are located on the
      interior surface of the capsid. In an attempt to understand the molecular
      mechanisms of adaptation of PV to mice, we investigated the effects of these two
      determinants on the viral multiplication cycle in a human cell line. Both
      determinants enhanced receptor-mediated conformational changes leading to altered
      particles of 135S, one of the first steps of uncoating, and viral
      internalization. Furthermore, the residue at position 22 of VP1 appears to
      facilitate RNA release. These results strongly suggest that these determinants
      could also facilitate conformational changes mediated by the PV murine receptor
      and internalization in the mouse nerve cell, thus allowing PV to overcome its
      host range restriction. Moreover, both mouse adaptation determinants are
      responsible for defects in the assembly of virions in human cells and affect the
      thermostability of the viral particles. Thus, these mouse adaptation determinants
      appear to control the balance between the viral capsid plasticity needed for the
      conformational changes in the early steps of infection and the structural
      requirements which are involved in the assembly and the stability of virions.

PMID- 8523542
TI  - Expression of an equine herpesvirus 1 ICP22/ICP27 hybrid protein encoded by
      defective interfering particles associated with persistent infection.
AB  - Defective interfering (DI) particles of equine herpesvirus type 1 (EHV-1) are
      capable of mediating persistent infection (S. A. Dauenhauer, R. A. Robinson, and
      D. J. O'Callaghan, J. Gen. Virol. 60:1-14, 1982; R. A. Robinson, R. B. Vance, and
      D. J. O'Callaghan, J. Virol. 36:204-219, 1980). Sequence analysis of cloned DI
      particle DNA revealed that portions of two regulatory genes, ICP22 (IR4) and
      ICP27 (UL3), are linked in frame to form a unique hybrid open reading frame
      (ORF). This hybrid ORF, designated as the IR4/UL3 gene, encodes the amino
      terminal 196 amino acids of the IR4 protein (ICP22 homolog) and the carboxy
      terminal 68 amino acids of the UL3 protein (ICP27 homolog). Portions of DNA
      sequences encoding these two regulatory proteins, separated by more than 115 kbp
      in the standard virus genome, were linked presumably by a homologous
      recombination event between two identical 8-bp sequences. Reverse transcriptase
      PCR and S1 nuclease analyses revealed that this unique ORF is transcribed by
      utilizing the transcription initiation site of ICP22 and the polyadenylation
      signal of ICP27 in DI particle-enriched infection. Immunoprecipitation and
      Western blot (immunoblot) analyses with antisera to the ICP22 and ICP27 proteins
      demonstrated that a 31-kDa hybrid protein was synthesized in the DI particle
      enriched infection but not in standard virus infection. This 31-kDa hybrid
      protein was expressed at the same time as the ICP22 protein in DI particle
      enriched infection and migrated at the same location on polyacrylamide gel
      electrophoresis as the protein expressed from a cloned IR4/UL3 expression vector.
      These observations suggested that the unique IR4/UL3 hybrid gene is expressed
      from the DI particle genome and may play a role in DI particle-mediated
      persistent infection.

PMID- 8523543
TI  - Analysis of the murine ecotropic leukemia virus receptor reveals a common
      biochemical determinant on diverse cell surface receptors that is essential to
      retrovirus entry.
AB  - Two residues, tyrosine 235 and glutamic acid 237, of the ecotropic murine
      leukemia virus receptor (ATRC1) have been shown to be essential for receptor
      mediated virus envelope binding and entry. We performed genetic analyses to
      examine the biochemical contribution of these residues in a productive virus
      receptor interaction. Altered ATRC1 receptors bearing either a phenylalanine, a
      tryptophan, a histidine, or a methionine at position 235 mediated ecotropic virus
      entry comparable to that mediated by ATRC1. In contrast, altered ATRC1 receptors
      bearing alanine, threonine, serine, or proline at position 235 exhibited a 300-
      to 10,000-fold decrease in receptor capability. Furthermore, substitution of
      tyrosine or phenylalanine into the corresponding position (242) of the homologous
      human protein that lacks ecotropic virus receptor capability resulted in
      acquisition of ecotropic virus receptor function comparable to that of ATRC1.
      Substitution of a tryptophan or a histidine at that position of the human
      protein, however, resulted in a much-reduced receptor capability, suggesting a
      preference for a benzene ring in the hydrophobic side chain. A similar analysis
      of proteins substituted at position 237 revealed that aspartic acid, but not
      arginine or lysine, can functionally substitute for glutamic acid 237 in ATRC1 or
      at the corresponding position in the human protein. These results suggest a
      requirement for an acidic and a nearby hydrophobic amino acid for efficient
      ecotropic virus entry. Similar motifs have been identified in the virus binding
      sites of other retrovirus receptors, suggesting that the initial step of
      retrovirus entry may be governed by a common mechanism.

PMID- 8523544
TI  - The A2L intermediate gene product is required for in vitro transcription from a
      vaccinia virus late promoter.
AB  - Previously, the in vitro late transcription system of vaccinia virus was resolved
      into four components: the 17- and 30-kDa products of the A1L and G8R intermediate
      genes, respectively, the viral DNA-dependent RNA polymerase, and an unmapped
      factor sedimenting at 32 to 38 kDa. Another protein, the 26-kDa product of the
      A2L open reading frame was predicted to be a late transcription factor on the
      basis of a transient-expression assay but was not recognized as being necessary
      for transcriptional activity in vitro. We now report that both the unmapped
      factor and the 26-kDa protein are required for transcription from a vaccinia
      virus late promoter in vitro. Since the 26-kDa protein has now been shown to be a
      trans-activator of late transcription and it is the product of a known gene, we
      suggest that it be designated VLTF-3.

PMID- 8523545
TI  - The human papillomavirus type 16 E7 protein complements adenovirus type 5 E1A
      amino-terminus-dependent transactivation of adenovirus type 5 early genes and
      increases ATF and Oct-1 DNA binding activity.
AB  - We have previously shown that conserved region 1 (CR1) of the adenovirus type 5
      (Ad5) E1A protein synergizes with CR3 in the transactivation of Ad5 early genes
      (H.K. Wong and E. B. Ziff, J. Virol. 68:4910-4920, 1994). CR1 lies within the E1A
      amino terminus and binds host regulatory proteins such as the RB protein, p107,
      p130, and p300. Since simian virus 40 (SV40) large T antigen and human
      papillomavirus type 16 (HPV16) E7 protein also bind host regulatory factors, we
      investigated whether these viral proteins can complement E1A mutants which are
      defective in early gene activation. We show that the HPV16 E7 protein but not
      SV40 T antigen can complement mutations in the Ad5 E1A CR1 in the transactivation
      of viral early promoters. The inability of SV40 T antigen to complement suggests
      that RB binding on its own is not sufficient for early promoter transactivation
      by the E1A amino terminus. Nuclear runoff assays show that complementation by
      HPV16 E7 restores the ability of the E1A mutants to stimulate early gene
      expression at the level of transcription. Furthermore, nuclear extracts from the
      E7-transformed cells show increased binding activity of ATF and Oct-1, factors
      that can recognize the elements of Ad5 early genes, consistent with gene
      activation by E1A and E7 at the transcriptional level.

PMID- 8523546
TI  - Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic
      tail required for envelope incorporation into virions.
AB  - We recently demonstrated that a single amino acid substitution in matrix residue
      12 (12LE) or 30 (30LE) blocks the incorporation of human immunodeficiency virus
      type 1 (HIV-1) envelope glycoproteins into virions and that this block can be
      reversed by pseudotyping with heterologous retroviral envelope glycoproteins with
      short cytoplasmic tails or by truncating the cytoplasmic tail of HIV-1
      transmembrane glycoprotein gp41 by 104 or 144 amino acids. In this study, we
      mapped the domain of the gp41 cytoplasmic tail responsible for the block to
      incorporation into virions by introducing a series of eight truncation mutations
      that eliminated 23 to 93 amino acids from the C terminus of gp41. We found that
      incorporation into virions of a HIV-1 envelope glycoprotein with a deletion of
      23, 30, 51, or 56 residues from the C terminus of gp41 is specifically blocked by
      the 12LE matrix mutation, whereas truncations of greater than 93 amino acids
      reverse this defect. To elucidate the role of matrix residue 12 in this process,
      we introduced a number of additional single amino acid substitutions at matrix
      positions 12 and 13. Charged substitutions at residue 12 blocked envelope
      incorporation and virus infectivity, whereas more subtle amino acid substitutions
      resulted in a spectrum of envelope incorporation defects. To characterize further
      the role of matrix in envelope incorporation into virions, we obtained and
      analyzed second-site revertants to two different matrix residue 12 mutations. A
      Val-->Ile substition at matrix amino acid 34 compensated for the effects of both
      amino acid 12 mutations, suggesting that matrix residues 12 and 34 interact
      during the incorporation of HIV-1 envelope glycoproteins into nascent virions.

PMID- 8523547
TI  - RNase of classical swine fever virus: biochemical characterization and inhibition
      by virus-neutralizing monoclonal antibodies.
AB  - The structural glycoprotein E0 of classical swine fever virus (CSFV) possesses an
      intrinsic RNase activity. Here we present the first comprehensive biochemical
      characterization of E0, using a recombinant glycoprotein expressed in insect
      cells. We were able to show that the presence of neither carbohydrate moieties
      nor disulfide bonds is a prerequisite for RNase activity. In addition, virus
      neutralizing and nonneutralizing anti-E0 monoclonal antibodies were tested for
      their ability to influence RNase activity. In these experiments, the antibodies
      which effectively blocked the infection of STE cells also exerted a high degree
      of E0 RNase inhibition. This correlation suggests that the RNase activity of CSFV
      E0 plays a role in the viral life cycle.

PMID- 8523548
TI  - Generation and role of defective proviruses in cytopathic feline leukemia virus
      (FeLV-FAIDS) infections.
AB  - Cytopathic feline leukemia virus (FeLV) infections of feline T-cell line (FeT
      cell) cultures led to the accumulation and maintenance of threefold more
      proviruses with deletions within the polymerase gene (pol) than minimally
      cytopathic FeLV infections. Over 60% of the viral DNA from cytopathic infections
      bore deletions in pol. Characterization of DNA sequences adjoining the deletions
      revealed that the junctions were most often flanked by RNA splice donor and
      acceptor consensus motifs. A thymidine-to-cytidine mutation introduced at the +2
      position of one RNA splice donor-like motif inhibited formation of the two most
      prevalent viral DNA species with deletions, confirming the origin of many
      proviruses with deletions from reverse transcription of aberrantly spliced viral
      RNA species. An example of deletion by misalignment was also characterized. Viral
      inocula obtained from cells recovered after cytopathic infections were attenuated
      in their ability to cause cytopathic effects (CPE) and were able to confer
      superinfection resistance to naive FeT-cells, despite maintaining envelope gene
      (env) sequences with full cytopathic potential. This suggested that viral genomes
      with deletions, rather than being required for cytopathicity, play a role in
      protecting cells from CPE. Indeed, expression of a molecularly cloned provirus
      bearing one of the characterized deletions attenuated CPE in FeT-cells caused by
      superinfecting cytopathic virus.

PMID- 8523549
TI  - Differing T-cell requirements for recombinant retrovirus vaccines.
AB  - Friend murine leukemia virus is a retrovirus complex that induces rapid
      erythroleukemia and immunosuppression in susceptible strains of adult mice. Using
      this model, we directly examined the T-cell subsets required for a protective
      retrovirus vaccine. Paradoxically, recovery in mice immunized with a chimeric
      envelope containing only T-helper (TH) and B-cell epitopes was dependent on CD8+
      T cells as well as CD4+ T cells despite the fact that the vaccine contained no
      CD8+ cytolytic T-lymphocyte (CTL) epitopes. However, the requirement for CD8+ T
      cells was overcome by inclusion of additional TH and B-cell epitopes in the
      immunizing protein. These additional epitopes primed for more rapid production of
      virus-neutralizing antibody which appeared to limit virus spread sufficiently to
      protect even in the absence of CD8+ T cells. Inclusion of an immunodominant CTL
      epitope in the vaccine was not sufficient to overcome dependence on CD4+ T cells.
      These data suggest that TH priming is more critical for retrovirus immunity than
      CTL priming.

PMID- 8523550
TI  - Directed integration of viral DNA mediated by fusion proteins consisting of human
      immunodeficiency virus type 1 integrase and Escherichia coli LexA protein.
AB  - We tested whether the selection of target sites can be manipulated by fusing
      retroviral integrase with a sequence-specific DNA-binding protein. A hybrid
      protein that has the Escherichia coli LexA protein fused to the C terminus of the
      human immunodeficiency virus type 1 integrase was constructed. The fusion
      protein, IN1-288/LA, retained the catalytic activities in vitro of the wild-type
      human immunodeficiency virus type 1 integrase (WT IN). Using an in vitro
      integration assay that included multiple DNA fragment as the target DNA, we found
      that IN1-288/LA preferentially integrated viral DNA into the fragment containing
      a DNA sequence specifically bound by LexA protein. No bias was observed when the
      LexA-binding sequence was absent, when the fusion protein was replaced by WT IN,
      or when LexA protein was added in the reaction containing IN1-288/LA. A majority
      of the integration events mediated by IN1-288/LA occurred within 30 bp of DNA
      flanking the LexA-binding sequence. The specificity toward the LexA-binding
      sequence and the distribution and frequency of target site usage were unchanged
      when the integrase component of the fusion protein was replaced with a variant
      containing a truncation at the N or C terminus or both, suggesting that the
      domain involved in target site selection resides in the central core region of
      integrase. The integration bias observed with the integrase-LexA hybrid shows
      that one effective means of altering the selection of DNA sites for integration
      is by fusing integrase to a sequence-specific DNA-binding protein.

PMID- 8523551
TI  - Multiple regulatory events influence human cytomegalovirus DNA polymerase (UL54)
      expression during viral infection.
AB  - The human cytomegalovirus (HCMV) DNA polymerase gene (UL54; also called pol) is a
      prototypical early gene in that expression is mandatory for viral DNA
      replication. Recently, we have identified the major regulatory element in the
      UL54 promoter responsive to the major immediate early (MIE) proteins (UL122 and
      UL123) (J.A. Kerry, M.A. Priddy, and R. M. Stenberg, J. Virol. 68:4167-4176,
      1994). Mutation of this element, inverted repeat sequence 1 (IR1), abrogates
      binding of cellular proteins to the UL54 promoter and reduces promoter activity
      in response to viral proteins in transient-transfection assays. To extend our
      studies on the UL54 promoter, we aimed to examine the role of IR1 in UL54
      regulation throughout the course of infection. These studies show that viral
      proteins in addition to the MIE proteins can activate the UL54 promoter. Proteins
      from UL112-113 and IRS1/TRS1, recently identified as essential loci for transient
      complementation of HCMV oriLyt-dependent DNA replication, were found to function
      as transactivators of the UL54 promoter in association with MIE proteins. UL112
      113 enhanced UL54 promoter activation by MIE proteins three- to fourfold.
      Constitutive expression of UL112-113 demonstrated that the MIE protein dependence
      of UL112-113 transactivational activity was not related to activation of cognate
      promoter sequences, suggesting that UL112-113 proteins function in cooperation
      with the MIE proteins. Mutation of IR1 was found to abrogate stimulation of the
      UL54 promoter by UL112-113, suggesting that this element is also involved in
      UL112-113 stimulatory activity. These results demonstrate that additional viral
      proteins influence UL54 promoter expression in transient-transfection assays via
      the IR1 element. To confirm the biological relevance of IR1 in regulating UL54
      promoter activity during viral infection, a recombinant virus construct
      containing the UL54 promoter with a mutated IR1 element regulating expression of
      the chloramphenicol acetyltransferase (CAT) reporter gene (RVIRmCAT) was
      generated. Analysis of RVIRmCAT revealed that mutation of IR1 dramatically
      reduces UL54 promoter activity at early times after infection. However, at late
      times after infection CAT expression by RVIRmCAT, as assessed by RNA and protein
      levels, was approximately equivalent to expression by wild-type RVpolCAT. These
      data demonstrate IR1-independent regulation of the UL54 promoter at late times
      after infection. Together these results show that multiple regulatory events
      affect UL54 promoter expression during the course of infection.

PMID- 8523552
TI  - Four of eleven loci required for transient complementation of human
      cytomegalovirus DNA replication cooperate to activate expression of replication
      genes.
AB  - As previously shown, 11 loci are required to complement human cytomegalovirus
      (HCMV) DNA replication in a transient-transfection assay (G. S. Pari and D. G.
      Anders, J. Virol. 67:6979-6988, 1993). Six of these loci encode known or
      candidate replication fork proteins, as judged by sequence and biochemical
      similarities to herpes simplex virus homologs of known function; three encode
      known immediate early regulatory proteins (UL36-38, IRS1/TRS1, and the major
      immediate early region spanning UL122-123); and two encode early, nucleus
      localized proteins of unknown functions (UL84 and UL112-113). We speculated that
      proteins of the latter five loci might cooperate to promote and regulate
      expression of the six replication fork proteins. To test this hypothesis we made
      luciferase reporter plasmids for each of the replication fork gene promoters and
      measured their activation by the candidate effectors, expressed under the control
      of their respective native promoters, using a transient-cooperativity assay in
      which the candidate effectors were subtracted individually from a transfection
      mixture containing all five loci. The combination of UL36-38, UL112-113, IRS1, or
      TRS1 and the major immediate early region produced as much as 100-fold-higher
      expression than the major immediate early region alone; omitting any one of these
      four loci from complementing mixtures produced a significant reduction in
      expression. In contrast, omitting UL84 had insignificant (less than twofold),
      promoter-dependent effects on reporter activity, and these data do not implicate
      UL84 in regulating HCMV early-gene expression. Most of the effector interactions
      showed significant positive cooperativity, producing synergistic enhancement of
      expression. Similar responses to these effectors were observed for the each of
      the promoters controlling expression of replication fork proteins. However,
      subtracting UL112-113 had little if any effect on expression by the UL112-113
      promoter or by the simian virus 40 promoter-enhancer under the same conditions.
      Several lines of evidence argue that the cooperative interactions observed in our
      transient-transfection assays are important to viral replication in permissive
      cells. Therefore, the data suggest a model in which coordinate expression of
      multiple essential replication proteins during permissive infection is vitally
      dependent upon the cooperative regulatory interactions of proteins encoded by
      multiple loci and thus have broad implications for our understanding of HCMV
      biology.

PMID- 8523553
TI  - Identification of EFIV, a stable factor present in many avian cell types that
      transactivates sequences in the 5' portion of the Rous sarcoma virus long
      terminal repeat enhancer.
AB  - We define a protein complex present in avian nuclear extracts that interacts with
      the Schmidt-Ruppin strain of the Rous sarcoma virus (RSV) long terminal repeat
      (LTR) between positions -197 and -168 relative to the transcriptional start site.
      We call this complex EFIV and demonstrate that the EFIV protein(s) is present in
      several avian cell types examined, including B cells (S13 and DT40), T cells
      (MSB), and chicken embryo fibroblasts. We also report that the EFIV binding site
      activates transcription of reporter constructs after transfection into avian B
      cells and chicken embryo fibroblasts, demonstrating that the EFIV region
      constitutes a functional transactivator sequence. By chemical interference
      footprinting and mutational analyses we define the EFIV binding site as including
      the sequence GCAACATG, which is present in two copies between positions -197 and 
      168, as well as sequences that lie between the two repeats. Electrophoretic
      mobility shift competition experiments suggest that the EFIV protein(s) may be
      related to members of the CCAAT/enhancer-binding protein family of transcription
      factors that interact with different regions of the RSV and the avian leukosis
      virus (ALV) LTRs. However, as defined by differences in sensitivity to protein
      synthesis inhibitors and footprinting patterns, EFIV is clearly distinct from
      these previously defined LTR binding factors. In addition, the finding that EFIV
      binding activity is stable in B cells indicates either that the lability of all
      5' LTR binding activities is not required for B-cell transformation by the
      ALV/RSV family of viruses or that nonacute transforming viruses that include an
      RSV LTR may use a mechanism to effect cellular transformation different from that
      proposed for ALV.

PMID- 8523554
TI  - AKR.H-2b lymphocytes inhibit the secondary in vitro cytotoxic T-lymphocyte
      response of primed responder cells to AKR/Gross murine leukemia virus-induced
      tumor cell stimulation.
AB  - We have previously shown that AKR.H-2b congenic mice, though carrying the
      responder H-2b major histocompatibility complex haplotype, are unable to generate
      secondary cytolytic T-lymphocyte (CTL) responses specific for AKR/Gross murine
      leukemia virus (MuLV). Our published work has shown that this nonresponsive state
      is specific and not due to clonal deletion or irreversible functional
      inactivation of antiviral CTL precursors. In the present study, an alternative
      mechanism based on the presence of inhibitory AKR.H-2b cells was examined.
      Irradiated or mitomycin C-treated AKR.H-2b spleen cells function as in vitro
      stimulator cells in the generation of C57BL/6 (B6) anti-AKR/Gross virus CTL,
      consistent with their expression of viral antigens. In contrast, untreated viable
      AKR.H-2b spleen cells functioned very poorly as stimulators in vitro. Viable
      AKR.H-2b spleen cells were also able to cause dramatic (up to > or = 25-fold)
      inhibition of antiviral CTL responses stimulated in vitro by standard AKR/Gross
      MuLV-induced tumor cells. This inhibition was specific: AKR.H-2b modulator spleen
      cells did not inhibit allogeneic major histocompatibility complex-specific CTL
      production, even when a concurrent antiviral CTL response in the same culture
      well was inhibited by the modulator cells. These results and those of experiments
      in which either semipermeable membranes were used to separate AKR.H-2b modulator
      spleen cells from AKR/Gross MuLV-primed responder cells or the direct transfer of
      supernatants from wells where inhibition was demonstrated to wells where there
      was antiviral CTL responsiveness argued against a role for soluble factors as the
      cause of the inhibition. Rather, the inhibition was dependent on direct contact
      of AKR.H-2b cells in a dose-dependent manner with the responder cell population.
      Inhibition was shown not to be due to the ability of AKR.H-2b cells to function
      as unlabeled competitive target cells. Exogenous interleukin-2 added at the onset
      of the in vitro CTL-generating cultures partially restored the antiviral response
      that was decreased by AKR.H-2b spleen cells. Positive and negative cell selection
      studies and the development of inhibitory cell lines indicated that B lymphocytes
      and both CD4- CD8+ and CD4+ CD8- T lymphocytes from AKR.H-2b mice could inhibit
      the generation of AKR/Gross virus-specific CTL in vitro. AKR.H-2b macrophages
      were shown not to be required to demonstrate AKR/Gross MuLV-specific inhibition,
      however, confirming that the inhibition by T-cell (or B-cell)-depleted spleen
      populations was dependent on the enriched B-cell (T-cell) population per
      se.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523555
TI  - Homologous RNA recombination in brome mosaic virus: AU-rich sequences decrease
      the accuracy of crossovers.
AB  - Brome mosaic virus, a tripartite positive-stranded RNA virus of plants, was used
      for the determination of sequence requirements of imprecise (aberrant) homologous
      recombination. A 23-nucleotide (nt) region that included a 6-nt UUAAAA sequence
      (designated the AU sequence) common between wild-type RNA2 and mutant RNA3
      supported both precise and imprecise homologous recombination, though the latter
      occurred with lower frequency. Doubling the length of the 6-nt AU sequence in
      RNA3 increased the incidence of imprecise crossovers by nearly threefold.
      Duplication or triplication of the length of the AU sequence in both RNA2 and
      RNA3 further raised the frequency of imprecise crossovers. The majority of
      imprecise crosses were located within or close to the extended AU sequence.
      Imprecise recombinants contained either nucleotide substitutions, nontemplated
      nucleotides, small deletions, or small sequence duplications within the region of
      crossovers. Deletion of the AU sequence from the homologous region in RNA3
      resulted in the accumulation of only precise homologous recombinants. Our results
      provide experimental evidence that AU sequences can facilitate the formation of
      imprecise homologous recombinants. The generation of small additions or deletions
      can be explained by a misannealing mechanism within the AU sequences, while
      replicase errors during RNA copying might explain the occurrence of nucleotide
      substitutions or nontemplated nucleotides.

PMID- 8523556
TI  - Inter- and intraclade neutralization of human immunodeficiency virus type 1:
      genetic clades do not correspond to neutralization serotypes but partially
      correspond to gp120 antigenic serotypes.
AB  - We have studied genetic variation among clades A through E of human
      immunodeficiency virus type 1 (HIV-1) at the levels of antibody binding to gp120
      molecules and virus neutralization. We are unable to identify neutralization
      serotypes that correspond to the genetic clades. Instead, we observe that inter-
      and intraclade neutralization of primary isolates by HIV-1-positive sera is
      generally weak and sporadic; some sera show a reasonable degree of neutralization
      breadth and potency whereas others are relatively sensitive to neutralization,
      but no consistent pattern was found. However, a few sera were able to neutralize
      across clades with significant potency, an observation which may have
      implications for the feasibility of a broadly effective HIV-1 vaccine involving
      humoral immunity. Serological assays measuring anti-gp120 antibody binding also
      failed to identify serotypes that correspond precisely to the genetic clades, but
      some indications of clade-specific binding were observed, notably with sera from
      clades B and E. A representative protein for each clade (A through E) was
      selected on the basis of its specificity, defined as high seroreactivity with
      sera from individuals infected with virus of that clade and lower reactivity with
      sera from individuals infected with viruses from other clades. The seroreactivity
      patterns against these five proteins could be used to predict the genotype of the
      infecting virus with moderate success.

PMID- 8523557
TI  - Quantitative analysis of serum neutralization of human immunodeficiency virus
      type 1 from subtypes A, B, C, D, E, F, and I: lack of direct correlation between
      neutralization serotypes and genetic subtypes and evidence for prevalent serum
      dependent infectivity enhancement.
AB  - Human immunodeficiency virus type 1 (HIV-1) M group strains have been assigned to
      date to nine distinct genetic subtypes, designated A through I, according to
      phylogenetic analyses of nucleotide sequences of their env or gag genes. Whether
      there is any relationship between phylogenetic subtypes and the neutralization
      serotypes is not clear, yet defining the nature of any such relationship by
      mathematical means would be of major importance for the development of globally
      effective HIV-1 vaccines. We have therefore developed a quantitative method to
      analyze serum neutralization of HIV-1 isolates and to identify HIV-1
      neutralization serotypes. This method involves calculations of the neutralization
      index, N(i), a newly defined parameter derived from plots generated from in vitro
      neutralization assays, calculations of pairwise serum-virus vector distances, and
      cluster analyses. We have applied this approach to analyze three independent
      neutralization matrices involving primary HIV-1 strains and sera from genetic
      subtypes A, B, C, D, E, F, and I. Detailed serum and HIV-1 isolate cluster
      analyses have shown that in general, the identified neutralization serotypes do
      not directly correlate with HIV-1 genetic subtypes. These results suggest that
      neutralization serotypes do not during natural HIV-1 infection are not governed
      by antibodies directed against simple epitopes within gp120 monomers. A
      significant proportion (28%) of 1,213 combinations of sera and HIV-1 isolates
      caused serum-dependent infectivity enhancement [negative N(i) values] rather than
      neutralization. We also noted that negative N(i) values tended to correlate
      better with certain HIV-1 isolates rather than with HIV-1-positive sera.
      Syncytium-inducing variants of HIV-1 were slightly more likely than non-syncytium
      inducing variants to undergo serum-dependent infectivity enhancement, although
      the latter variants could clearly be susceptible to enhancement.

PMID- 8523558
TI  - Role of the mu 1 protein in reovirus stability and capacity to cause chromium
      release from host cells.
AB  - The reovirus M2 gene is associated with the capacity of type 3 strain Abney (T3A)
      intermediate subviral particles (ISVPs) to permeabilize cell membranes as
      measured by chromium (51Cr) release (P. Lucia-Jandris, J. W. Hooper, and B. N.
      Fields, J. Virol. 67:5339-5345, 1993). In addition, reovirus mutants with lesions
      in the M2 gene can be selected by heating virus at 37 degrees C for 20 min in 33%
      ethanol (D. R. Wessner and B. N. Fields, J. Virol. 67:2442-2447, 1993). In this
      report we investigated the mechanism by which the reovirus M2 gene product (the
      mu 1 protein) influences the capacity of reovirus ISVPs to permeabilize
      membranes, using ethanol-selected T3A mutants. Each of three T3A ethanol
      resistant mutants isolated (JH2, JH3, and JH4) exhibited a decreased capacity to
      cause 51Cr release relative to that of wild-type T3A. Sequence analysis of the M2
      genes of wild-type T3A and the T3A mutants indicated that each mutant possesses a
      single amino acid substitution in a central region of the 708-amino-acid mu 1
      protein: JH2 (residue 466, Tyr to Cys), JH3 (residue 459, Lys to Glu), and JH4
      (residue 497 Pro to Ser). Assays performed with reovirus natural isolates,
      reassortants, and a set of previously characterized type 3 strain Dearing (T3D)
      ethanol-resistant mutants revealed a strong correlation between ethanol
      sensitivity and the capacity to cause 51Cr release. We found that ISVPs generated
      from the T3A and T3D mutants were stable when heated to 50 degrees C, whereas
      wild-type T3A ISVPs are inactivated under these conditions. Together, these data
      suggest that amino acid substitutions in a central region of the mu 1 protein
      affect the capacity of the ISVP to permeabilize L-cell membranes by altering the
      stability of the virus particle.

PMID- 8523559
TI  - Extraction of nuclei from sonchus yellow net rhabdovirus-infected plants yields a
      polymerase that synthesizes viral mRNAs and polyadenylated plus-strand leader
      RNA.
AB  - Although the primary sequence of the genome of the plant rhabdovirus sonchus
      yellow net virus (SYNV) has been determined, little is known about the
      composition of the viral polymerase or the mechanics of viral transcription and
      replication. In this paper, we report the partial isolation and characterization
      of an active SYNV polymerase from nuclei of SYNV-infected leaf tissue. A salt
      extraction procedure is shown to be an effective purification step for recovery
      of the polymerase from the nuclei. Full-length, polyadenylated SYNV N and M2
      mRNAs and plus-strand leader RNA are among the products of the in vitro
      polymerase reactions. Polyadenylation of the plus-strand leader RNA in vitro is
      shown with RNase H and specific oligonucleotides. This is the first report of a
      polyadenylated plus-strand leader RNA for a minus-strand RNA virus, a feature
      that may reflect adaptation of SYNV to replication in the nucleus. Analysis of
      the SYNV proteins present in the polymerase extract suggests that the N, M2, and
      L proteins are components of the transcription complex. Overall, the system we
      developed promises to be useful for an in-depth characterization of the mechanics
      of SYNV RNA synthesis.

PMID- 8523560
TI  - Phenotypic characterization of mutants in vaccinia virus gene G2R, a putative
      transcription elongation factor.
AB  - The phenotypic defects of two mutants of vaccinia virus, the lesions of which map
      to gene G2R, were characterized in vivo, and the results suggest a role for the
      G2R protein in viral transcription elongation. Both a temperature-sensitive
      mutant, Cts56, and an isatin-beta-thiosemicarbazone-dependent deletion mutant,
      G2A, in gene G2R have a characteristic and unique defect in late viral gene
      expression. The G2R mutants synthesize early viral RNA, early viral proteins, and
      viral DNA normally under nonpermissive conditions. In G2R mutants, late viral
      protein synthesis begins at the normal time, low-molecular-weight viral proteins
      are synthesized in normal quantities, but synthesis of high-molecular-weight
      viral proteins is reduced in amount. Intermediate and late promoter utilization
      is normal in G2R mutants, but intermediate and late RNAs are reduced in size. The
      reduction in length of the intermediate and late mRNAs represents a truncation of
      mRNA 3' ends. Thus, intermediate and late RNAs are too short to encode large
      proteins but long enough to encode small proteins, therefore accounting for the
      protein synthesis phenotype. These results suggest that the G2R protein acts to
      regulate the elongation potential of the viral RNA polymerase late during a
      vaccinia virus infection.

PMID- 8523561
TI  - In vivo restoration of biologically active 3' ends of virus-associated RNAs by
      nonhomologous RNA recombination and replacement of a terminal motif.
AB  - Sequences at the 3' ends of plus-strand RNA viruses and their associated subviral
      RNAs are important cis elements for the synthesis of minus strands in vivo and in
      vitro. All RNAs associated with turnip crinkle virus (TCV), including the genomic
      RNA (4,054 bases) and satellite RNAs (sat-RNAs) such as sat-RNA D (194 bases),
      terminate with the motif CCUGCCC. While investigating the ability of in vivo
      generated recombinants between sat-RNA D and TCV to be amplified in plants, we
      discovered that sat-RNA D, although truncated by as many as 15 bases in the
      chimeric molecules, was released from the chimeric transcripts and amplified to
      high levels. The "new" sat-RNA D molecules nearly all terminated with the motif
      (C1-2)UG(C1-3) (which may begin with 1 or 2 cytosines and end with 1, 2, or 3
      cytosines), which was similar or identical to the natural sat-RNA D 3' end. The
      new sat-RNA D also contained between 1 and 22 bases of heterogeneous sequence
      upstream from the terminal motif, which, in some cases, was apparently derived
      from internal regions of either the plus or minus strand of the TCV genomic RNA.
      Since most of these internal genomic RNA sequences within TCV were not adjacent
      to (C1-2)UG(C1-3), at least two steps were required to produce new sat-RNA D 3'
      ends: nonhomologous recombination with the TCV genomic RNA followed by the
      addition or modification of the terminus to generate the (C1-2)UG(C1-3) motif.

PMID- 8523562
TI  - Genetic mapping indicates that VP4 is the rotavirus cell attachment protein in
      vitro and in vivo.
AB  - To identify the rotavirus protein which mediates attachment to cells in culture,
      viral reassortants between the simian rotavirus strain RRV and the murine strains
      EHP and EW or between the simian strain SA-11 and the human strain DS-1 were
      isolated. These parental strains differ in the requirement for sialic acid to
      bind and infect cells in culture. Infectivity and binding assays with the
      parental and reassortant rotaviruses indicate that gene 4 encodes the rotavirus
      protein which mediates attachment to cells in culture for both sialic acid
      dependent and -independent strains. Using ligated intestinal segments of newborn
      mice and reassortants obtained between the murine strain EW and RRV, we developed
      an in vivo infectivity assay. In this system, the infectivity of EW was not
      affected by prior treatment of the enterocytes with neuraminidase, while
      neuraminidase treatment reduced the infectivity of a reassortant carrying gene 4
      from RRV on an EW background more than 80% relative to the controls. Thus, VP4
      appears to function as the cell attachment protein in vivo as well as in vitro.

PMID- 8523563
TI  - Cytoskeleton association and virion incorporation of the human immunodeficiency
      virus type 1 Vif protein.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vif protein has an important role
      in the regulation of virus infectivity. This function of Vif is cell type
      specific, and virions produced in the absence of Vif in restrictive cells have
      greatly reduced infectivity. We show here that the intracellular localization of
      Vif is dependent on the presence of the intermediate filament vimentin.
      Fractionation of acutely infected T cells or transiently transfected HeLa cells
      demonstrates the existence of a soluble and a cytoskeletal form and to a lesser
      extent the presence of a detergent-extractable form of Vif. Confocal microscopy
      suggests that in HeLa cells, Vif is predominantly present in the cytoplasm and
      closely colocalizes with the intermediate filament vimentin. Treatment of cells
      with drugs affecting the structure of vimentin filaments affect the localization
      of Vif accordingly, indicating a close association of Vif with this cytoskeletal
      component. The association of Vif with vimentin can cause the collapse of the
      intermediate filament network into a perinuclear aggregate. In contrast, analysis
      of Vif in vimentin-negative cells reveals significant staining of the nucleus and
      the nuclear membrane in addition to diffuse cytoplasmic staining. In addition to
      the association of Vif with intermediate filaments, analyses of virion
      preparations demonstrate that Vif is incorporated into virus particles. In
      sucrose density gradients, Vif cosediments with capsid proteins even after
      detergent treatment of virus preparations, suggesting that Vif is associated with
      the inner core of HIV particles. We propose a model in which Vif has a crucial
      function as a virion component either by regulating virus maturation or following
      virus entry into a host cell possibly involving an interaction with the cellular
      cytoskeletal network.

PMID- 8523564
TI  - Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene
      transfer.
AB  - Several DNA-based Sindbis virus vectors were constructed to investigate the
      feasibility and potential applications for initiating the virus life cycle in
      cells transfected directly with plasmid DNA. These vectors, when transfected into
      mammalian cells, have been used to produce virus, to express heterologous genes,
      and to produce infectious vector particles. This approach involved the conversion
      of a self-replicating vector RNA (replicon) into a layered DNA-based expression
      system. The first layer includes a eukaryotic RNA polymerase II expression
      cassette that initiates nuclear transcription of an RNA which corresponds to the
      Sindbis virus vector replicon. Following transport of this RNA from the nucleus
      to the cytoplasm, the second layer, autocatalytic amplification of the vector,
      proceeds according to the Sindbis virus replication cycle and results in
      expression of the heterologous gene. The Sindbis virus DNA vectors expressed
      reporter genes in transfected cells at levels that were comparable to those of in
      vitro-transcribed RNA replicons and were approximately 10-fold higher than the
      levels produced by conventional RNA polymerase II-dependent plasmids in which the
      promoter and reporter gene were linked directly. Reporter gene expression was
      also observed in rodent muscle following injection with Sindbis virus DNA
      vectors. In a second application, packaged vector particles were produced in
      cells cotransfected with complementing replicon and defective helper DNAs. The
      Sindbis virus-derived DNA vectors described here increase the utility of
      alphavirus-based vector systems in general and also provide a vector with broad
      potential applications for genetic immunization.

PMID- 8523565
TI  - Transduction with recombinant adeno-associated virus for gene therapy is limited
      by leading-strand synthesis.
AB  - Adeno-associated virus is an integrating DNA parvovirus with the potential to be
      an important vehicle for somatic gene therapy. A potential barrier, however, is
      the low transduction efficiencies of recombinant adeno-associated virus (rAAV)
      vectors. We show in this report that adenovirus dramatically enhances rAAV
      transduction in vitro in a way that is dependent on expression of early region 1
      and 4 (E1 and E4, respectively) genes and directly proportional to the appearance
      of double-stranded replicative forms of the rAAV genome. Expression of the open
      reading frame 6 protein from E4 in the absence of E1 accomplished a similar but
      attenuated effect. The helper activity of adenovirus E1 and E4 for rAAV gene
      transfer was similarly demonstrated in vivo by using murine models of liver- and
      lung-directed gene therapy. Our data indicate that conversion of a single
      stranded rAAV genome to a duplex intermediate limits transduction and usefulness
      for gene therapy.

PMID- 8523566
TI  - Identification of a minimal hydrophobic domain in the herpes simplex virus type 1
      scaffolding protein which is required for interaction with the major capsid
      protein.
AB  - Recent biochemical and genetic studies have demonstrated that an essential step
      of the herpes simplex virus type 1 capsid assembly pathway involves the
      interaction of the major capsid protein (VP5) with either the C terminus of the
      scaffolding protein (VP22a, ICP35) or that of the protease (Pra, product of
      UL26). To better understand the nature of the interaction and to further map the
      sequence motif, we expressed the C-terminal 30-amino-acid peptide of ICP35 in
      Escherichia coli as a glutathione S-transferase fusion protein (GST/CT). Purified
      GST/CT fusion proteins were then incubated with 35S-labeled herpes simplex virus
      type 1-infected cell lysates containing VP5. The interaction between GST/CT and
      VP5 was determined by coprecipitation of the two proteins with glutathione
      Sepharose beads. Our results revealed that the GST/CT fusion protein specifically
      interacts with VP5, suggesting that the C-terminal domain alone is sufficient for
      interaction with VP5. Deletion analysis of the GST/CT binding domain mapped the
      interaction to a minimal 12-amino-acid motif. Substitution mutations further
      revealed that the replacement of hydrophobic residues with charged residues in
      the core region of the motif abolished the interaction, suggesting that the
      interaction is a hydrophobic one. A chaotropic detergent, 0.1% Nonidet P-40, also
      abolished the interaction, further supporting the hydrophobic nature of the
      interaction. Computer analysis predicted that the minimal binding motif could
      form a strong alpha-helix structure. Most interestingly, the alpha-helix model
      maximizes the hydropathicity of the minimal domain so that all of the hydrophobic
      residues are centered around a Phe residue on one side of the alpha-helix.
      Mutation analysis revealed that the Phe residue is absolutely critical for the
      binding, since changes to Ala, Tyr, or Trp abrogated the interaction. Finally, in
      a peptide competition experiment, the C-terminal 25-amino-acid peptide, as well
      as a minimal peptide derived from the binding motif, competed with GST/CT for
      interaction with VP5. In addition, a cyclic analog of the minimal peptide which
      is designed to stabilize an alpha-helical structure competed more efficiently
      than the minimal peptide. The evidence suggests that the C-terminal end of ICP35
      forms an alpha-helical secondary structure, which may bind specifically to a
      hydrophobic pocket in VP5.

PMID- 8523567
TI  - Reovirus infection in rat lungs as a model to study the pathogenesis of viral
      pneumonia.
AB  - We undertook the present study to elucidate the pathogenesis of the pathologic
      response to reovirus infection in the lungs and further understand the
      interactions of reoviruses with pulmonary cells. We found that reoviruses were
      capable of causing acute pneumonia in 25- to 28-day-old Sprague-Dawley rats
      following intratracheal inoculation with the reoviruses type 1 Lang (T1L) and
      type 3 Dearing (T3D). The onset of the pneumonia was rapid, marked by type I
      alveolar epithelial cell degeneration, type II alveolar epithelial cell
      hyperplasia, and the infiltration of leukocytes into the alveolar spaces. More
      neutrophils were recruited into the lungs during T3D infection than during T1L
      infection, and the serotype difference in the neutrophil response was mapped to
      the S1 gene of reovirus. Viral replication in the lungs was required for the
      development of pneumonia due to T1L and T3D infections, and replication occurred
      in type I alveolar epithelial cells. T1L grew to higher titers in the lungs than
      did either T3D or type 3 clone 9, and the S1 gene was found to play a role in
      determining the level of viral replication. We propose that experimental reovirus
      infection in the lungs can serve as a model for the pathogenesis of viral
      pneumonia in which pulmonary inflammation results following direct infection of
      lung epithelial cells.

PMID- 8523569
TI  - Complete inhibition of virion assembly in vivo with mutant procapsid RNA
      essential for phage phi 29 DNA packaging.
AB  - A highly efficient method for the inhibition of bacteriophage phi 29 assembly was
      developed with the use of mutant forms of the viral procapsid (or packaging) RNA
      (pRNA) indispensable for phi 29 DNA packaging. Phage phi 29 assembly was severely
      reduced in vitro in the presence of mutant pRNA and completely blocked in vivo
      when the host cell expressed mutant pRNA. Addition of 45% mutant pRNA resulted in
      a reduction of infectious virion production by 4 orders of magnitude, indicating
      that factors involved in viral assembly can be targets for efficient and specific
      antiviral treatment. The mechanism leading to the high efficiency of inhibition
      was attributed to two pivotal features. First, the pRNA contains two separate,
      essential functional domains, one for procapsid binding and the other for a DNA
      packaging role other than procapsid binding. Mutation of the DNA-packaging domain
      resulted in a pRNA with no DNA-packaging activity but intact procapsid binding
      competence. Second, multiple copies of the pRNA were involved in the packaging of
      one genome. This higher-order dependence of pRNA in viral replication
      concomitantly resulted in its higher-order inhibitory effect. This finding
      suggested that the collective DNA-packaging activity of multiple copies of pRNA
      could be disrupted by the incorporation of perhaps an individual mutant pRNA into
      the group. Although this mutant pRNA could not be used for the inhibition of the
      replication of other viruses directly, the principle of using molecules with two
      functional domains and multiple-copy involvement as targets for antiviral agents
      could be applied to certain viral structural proteins, enzymes, and other factors
      or RNAs involved in the viral life cycle. This principle also implies a strategy
      for gene therapy, intracellular immunization, or construction of transgenic
      plants resistant to viral infection.

PMID- 8523568
TI  - Primary characterization of a herpesvirus agent associated with Kaposi's
      sarcomae.
AB  - Detection of novel DNA sequences in Kaposi's sarcoma (KS) and AIDS-related body
      cavity-based, non-Hodgkin's lymphomas suggests that these neoplasms are caused by
      a previously unidentified human herpesvirus. We have characterized this agent
      using a continuously infected B-lymphocyte cell line derived from an AIDS-related
      lymphoma and a genomic library made from a KS lesion. In this cell line, the
      agent has a large episomal genome with an electrophoretic mobility similar to
      that of 270-kb linear DNA markers during clamped homogeneous electric field gel
      electrophoresis. A 20.7-kb region of the genome has been completely sequenced,
      and within this region, 17 partial and complete open reading frames are present;
      all except one have sequence and positional homology to known gammaherpesvirus
      genes, including the major capsid protein and thymidine kinase genes.
      Phylogenetic analyses using both single genes and combined gene sets demonstrated
      that the agent is a gamma-2 herpesvirus (genus Rhadinovirus) and is the first
      member of this genus known to infect humans. Evidence for transient viral
      transmission from infected to uninfected cells is presented, but replication
      competent virions have not been identified in infected cell lines. Sera from
      patients with KS have specific antibodies directed against antigens of infected
      cell lines, and these antibodies are generally absent in sera from patients with
      AIDS without KS. These studies define the agent as a new human herpesvirus
      provisionally assigned the descriptive name KS-associated herpesvirus; its formal
      designation is likely to be human herpesvirus 8.

PMID- 8523570
TI  - Efficient dual transcomplementation of adenovirus E1 and E4 regions from a 293
      derived cell line expressing a minimal E4 functional unit.
AB  - Transgene expression after the administration of recombinant adenovirus with E1
      deleted is constantly transient. It is admitted that E1A-substituting activities
      of cellular or viral origin allow viral antigen synthesis and trigger cytotoxic
      lymphocyte-mediated clearance of the recipient cells. Our approach to solving
      this problem relies on the additional deletion of the E4 region from the vector
      backbone as this region upregulates viral gene expression at both transcriptional
      and posttranscriptional levels. As a prerequisite to the construction of E1 E4
      doubly defective adenoviruses, we investigated the possibility of
      transcomplementing both functions within a single cell. In particular, the distal
      ORF6+ORF7 segment from the E4 locus of adenovirus type 5 was cloned under the
      control of the dexamethasone-inducible mouse mammary tumor virus long terminal
      repeat. Following transfection into 293 cells, clone IGRP2 was retained and
      characterized as it can rescue the growth defect of all E1+ E4- adenoviral
      deletants tested. DNA and RNA analysis experiments verified that the mouse
      mammary tumor virus promoter drives the expression of the ORF6+ORF7 unit and
      permits its bona fide alternative splicing, generating ORF6/7 mRNA in addition to
      the ORF6-expressing primary transcript. Importantly, IGRP2 cells sustain cell
      confluence for a period longer than that of 293 parental cells and allow the
      plaque purification of E1- or E4- defective viruses. The dual expression of E1
      and E4 regulatory genes within IGRP2 cells is demonstrated by the construction,
      plaque purification, and helper-free propagation of recombinant lacZ-encoding
      doubly defective adenoviruses harboring different E4 deletions. In addition, the
      emergence, if any, of replicative particles during viral propagation in this
      novel packaging cell line will be drastically impaired as only a limited segment
      of E4 has been integrated.

PMID- 8523571
TI  - Relationship between tumor necrosis factor alpha and feline immunodeficiency
      virus expressions.
AB  - The presence of feline immunodeficiency virus (FIV) proviral DNA, expression of
      FIV p26 core protein, and production of tumor necrosis factor alpha (TNF-alpha)
      were assessed in sequential biopsies of spleen and lymph node sections, of
      mononuclear cells of the peripheral blood, and of the serum of specific-pathogen
      free cats during the acute phase of FIV infection. A temporal relationship
      between TNF-alpha production and FIV p26 expression was noted. Two months
      following FIV infection, and preceding the detection of FIV viremia, levels of
      TNF-alpha in serum increased significantly (P = 0.04), and they remained elevated
      during FIV viremia in the third month postinfection. Immunoprecipitates
      representing expression of TNF-alpha and of FIV p26 were localized in common foci
      of lymph nodes of FIV-infected cats during this period of active viremia. With
      the advent of anti-FIV antibodies, circulating levels of TNF-alpha and p26
      antigen and expression of TNF-alpha and p26 in the lymph nodes decreased during
      the fifth month postinfection, and p26 production became undetectable. With
      clearance of viremia, burden of proviral DNA in peripheral blood mononuclear
      cells became reduced (P = 0.041), with provirus remaining integrated principally
      within lymph nodes (P = 0.046). During aviremia, p26 expression was undetectable
      in any tissue but remained inducible in vitro. During acute FIV infection, TNF
      alpha production and p26 expression are intimately linked.

PMID- 8523572
TI  - Induction of interleukin-6 after stimulation of human B-cell CD21 by Epstein-Barr
      virus glycoproteins gp350 and gp220.
AB  - The cellular receptor for Epstein-Barr virus (EBV) is the type 2 complement
      receptor, CD21. At initial infection, EBV virion glycoproteins gp350 and gp220
      bind to CD21. We report here that the cross-linking of CD21 by gp350/220 results
      in increased amounts of interleukin 6 (IL-6) RNA and IL-6 protein. This effect
      could be blocked with anti-gp350/220 and anti-CD21 monoclonal antibodies.
      Induction of IL-6 in B cells by EBV could be mimicked by treatment with the
      protein kinase C (PKC) activator phorbol 12,13-dibutyrate but not with the
      calcium ionophore ionomycin. IL-6 induction by EBV was inhibited with the PKC
      specific inhibitor bisindolylmaleimide or the protein tyrosine kinase inhibitors
      methyl 2,5-dihydroxycinnamate and herbimycin A, indicating that the induction of
      IL-6 following CD21 cross-linking is mediated through PKC- and protein tyrosine
      kinase-dependent pathways.

PMID- 8523573
TI  - The entry of reovirus into L cells is dependent on vacuolar proton-ATPase
      activity.
AB  - Inhibitors of vacuolar proton-ATPase activity (5 microM bafilomycin A1 or 50 nM
      concanamycin A) prevented infection by reovirus particles but not by infectious
      subviral particles (ISVPs). Neither compound affected virus attachment or
      internalization. However, both compounds potently blocked cleavage of the viral
      protein mu 1C. Finally, both reovirus particles and ISVPs efficiently
      translocated the toxin alpha-sarcin to the cytosol during virus entry.
      Bafilomycin A1 blocked translocation of alpha-sarcin by reovirus particles but
      not by ISVPs.

PMID- 8523575
TI  - Specific hepatitis B virus minus-strand DNA synthesis requires only the 5'
      encapsidation signal and the 3'-proximal direct repeat DR1.
AB  - Human hepatitis B virus (HBV) is a small DNA virus that replicates inside the
      viral nucleocapsid by reverse transcription of an RNA intermediate, the
      pregenome. The sequences encompassing the encapsidation signal epsilon and the
      direct repeat DR1 are present in two copies of this terminally redundant
      transcript. We have recently shown that HBV minus-strand DNA synthesis involves
      transfer of a short DNA primer copied from 5'-epsilon to 3'-DR1 (DR1*). Using
      transfection of HBV genomes with lesions in 3'-epsilon, and 5'-DR1 and its
      preceding sequence, we tested whether these additional elements contribute to the
      specificity of the transfer reaction. However, while some mutations affected
      proper plus-strand DNA formation, 5'-epsilon and DR1* were completely sufficient
      for correct minus-strand DNA production.

PMID- 8523574
TI  - Temperature-sensitive phenotype of the human parainfluenza virus type 3 candidate
      vaccine strain (cp45) correlates with a defect in the L gene.
AB  - We have previously demonstrated that the temperature sensitivity of a human
      parainfluenza virus type 3 (HPIV-3) candidate vaccine strain (cp45), which is
      currently under evaluation in humans, is associated with poor transcriptional
      activity of the virus at the nonpermissive temperature (R. Ray, K. Meyer, F.
      Newman, and R. B. Belshe, J. Virol. 69:1959-1963, 1995). In this study, the
      temperature sensitivity of cp45 virus was further investigated by the
      complementation of a specific gene function. CV-1 cells were transfected with
      cloned genes from wild-type HPIV-3 encoding the large protein (L), phosphoprotein
      (P), and nucleocapsid protein (NP), alone or together, for the expression of
      biologically active proteins. Only cells expressing the L gene were able to
      rescue cp45 replication when incubated at the nonpermissive temperature (39.5
      degrees C), whereas cells transiently expressing NP or P were incapable of
      rescuing the virus. The virus titers obtained following complementation of the L
      protein were 190 to 2,300 PFU/ml of culture medium, compared with the
      undetectable growth of the cp45 temperature-sensitive mutant at the nonpermissive
      temperature. Rescued progeny virus still maintained the temperature-sensitive
      phenotype. Results from this study suggest that the temperature sensitivity of
      the cp45 candidate vaccine strain is associated primarily with L-protein function
      and that the defect can be complemented by transient expression of the wild-type
      protein. This study underscores the importance of the L protein in RNA polymerase
      activity and its critical role in virus replication.

PMID- 8523576
TI  - Equine infectious anemia virus replication is upregulated during differentiation
      of blood monocytes from acutely infected horses.
AB  - Equine infectious anemia virus is a lentivirus that replicates in mature tissue
      macrophages of horses. Ponies were infected with equine infectious anemia virus.
      During febrile episodes, proviral DNA was detectable, but viral mRNA was not
      detectable. As cultured blood monocytes from these ponies differentiated into
      macrophages, viral expression was upregulated. In situ hybridization confirmed
      that viral transcription occurred in mature macrophages.

PMID- 8523577
TI  - Activation of caprine arthritis-encephalitis virus long terminal repeat by gamma
      interferon.
AB  - Caprine arthritis-encephalitis virus (CAEV) is a lymphotropic lentivirus whose
      replication increases during monocyte maturation. We examined gene expression
      directed by the CAEV long terminal repeat (LTR) in a promonocytic cell line
      stimulated with several agents. Our results demonstrate that the CAEV LTR is
      activated by treatment of immature monocytes with gamma interferon (IFN-gamma) or
      a phorbol ester but not with tumor necrosis factor alpha or lipopolysaccharide.
      The cis-acting element in the LTR for the IFN-gamma response localizes to a
      duplicated 70-bp motif that contains an IFN-gamma response element, the gamma
      activated site. One copy of the motif is necessary and sufficient for the
      response to IFN-gamma. Multiple copies contribute to basal transcriptional
      activity in the context of a heterologous promoter. This IFN-gamma response
      element in the CAEV LTR differs from the element required for the response to
      phorbol esters. Thus, activation of the CAEV LTR in monocytes that are stimulated
      by IFN-gamma, a cytokine that is secreted in response to viral infections, could
      contribute to conversion from latent to high-level viral replication in infected
      hosts.

PMID- 8523578
TI  - A herpesvirus saimiri membrane protein required for interleukin-2 independence
      forms a stable complex with p56lck.
AB  - ORF-2, a 32-kDa viral protein expressed by herpesvirus saimiri-transformed
      lymphocytes, is essential for transformation and is expressed on the plasma
      membrane of transformed cells. The current work now shows that most
      (approximately 80%) of ORF-2 resides in the cytoplasm, while only a small portion
      protrudes from the cell surface. Expressed as a glutathione S-transferase fusion
      protein, ORF-2 was found to interact with a 56-kDa cellular protein in
      untransformed, herpesvirus saimiri-transformed, and Jurkat lymphocytes.
      Microsequencing proved that this protein is the lymphocyte-specific tyrosine
      protein kinase p56lck. Two regions of ORF-2 were found to be required for p56lck
      interaction. Current evidence suggests that the interaction of ORF-2 with p56lck
      plays a key role in the specific transformation of T lymphocytes to an
      interleukin-2-independent phenotype.

PMID- 8523579
TI  - Single amino acid substitution in constant region 1 or 4 of gp120 causes the
      phenotype of a human immunodeficiency virus type 1 variant with mutations in
      hypervariable regions 1 and 2 to revert.
AB  - The second major cysteine loop of human immunodeficiency virus type 1 envelope
      glycoprotein gp120 contains 5 to 11 consensus N-linked glycosylation sites, which
      is disproportionately higher than the number of such sites found in other regions
      of gp120. Amino acid substitutions introduced at three of six N-linked
      glycosylation sites in this region of an infectious molecular clone, HXB2,
      resulted in severe impairment of virus infectivity. Isolation and genetic
      characterization of a revertant of this mutant revealed an isoleucine-for-valine
      substitution at position 84 in constant region 1 and an isoleucine-for-methionine
      substitution at position 434 in constant region 4. Further mutational analysis
      indicated that either isoleucine substitution was sufficient to confer the
      revertant phenotype. These findings demonstrate that V1/V2 not only functionally
      interacts with C4, as previously reported, but also interacts with C1. The
      observation that compensatory changes do not involve regeneration of N-linked
      glycosylation sites in the second major cysteine loop suggests that replication
      of human immunodeficiency virus type 1 in vitro is independent of the presence of
      a disproportionate number of N-linked glycosylation sites within this loop.

PMID- 8523580
TI  - The v-erbB oncogene confers enhanced cellular susceptibility to reovirus
      infection.
AB  - We have previously demonstrated that two mouse cell lines that are poorly
      infectible by reovirus become highly susceptible upon transfection with the gene
      encoding the epidermal growth factor receptor (EGFR) (J. E. Strong, D. Tang, and
      P. W. K. Lee, Virology 197:405-411, 1993). This enhancement of infection
      efficiency requires a functional EGFR, since such an enhancement is not observed
      in cells expressing a mutated (kinase-inactive) EGFR. The additional finding that
      reovirus is capable of directly binding to the N-terminal ectodomain of the EGFR
      (D. Tang, J. E. Strong, and P. W. K. Lee, Virology 197:412-414, 1993) has led us
      to question whether this interaction is required for the activation of a
      signalling cascade that somehow augments the ensuing infection process. In the
      present study, we address this question, using cells transfected with the v-erbB
      oncogene, which encodes a protein structurally related to the EGFR but lacking a
      large portion of the N-terminal ligand-binding domain. The v-erbB protein also
      possesses ligand-independent, constitutive tyrosine kinase activity. Control NIH
      3T3 cells, which are poorly infectible by reovirus (serotype 3, strain Dearing),
      and NIH 3T3 cells transfected with the v-erbB oncogene (THC-11) were assayed for
      their susceptibilities to reovirus infection. Infectivity was determined by
      immunofluorescent detection of viral proteins, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis of radiolabeled cells, and plaque
      titration. All three assays demonstrated a drastically higher degree of
      susceptibility to infection in the THC-11 cell line. This enhanced susceptibility
      was found to be abrogated by treatment of the cells with genistein, an inhibitor
      of tyrosine protein kinases, but only partially by treatment with daidzein, an
      inactive analog of genistein. We propose that the mechanism of enhancement of
      infection efficiency conferred by EGFR and v-erbB is through the opportunistic
      utilization by the virus of an already activated signal transduction pathway.

PMID- 8523581
TI  - Vaccination protects against in vivo-grown feline immunodeficiency virus even in
      the absence of detectable neutralizing antibodies.
AB  - So far, vaccination experiments against feline immunodeficiency virus have used
      in vitro-grown virus to challenge the vaccinated hosts. In this study, cats were
      vaccinated with fixed feline immunodeficiency virus-infected cells and challenged
      with plasma obtained from cats infected with the homologous virus diluted to
      contain 10 cat 50% infectious doses. As judged by virus culture, PCRs, and
      serological analyses performed over an 18-month period after the challenge, all
      of the vaccinated cats were clearly protected. Interestingly, prior to challenge
      most vaccines lacked antibodies capable of neutralizing a fresh isolate of the
      homologous virus.

PMID- 8523582
TI  - Self-contained, tetracycline-regulated retroviral vector system for gene delivery
      to mammalian cells.
AB  - Retroviral vectors that contain the tetracycline-inducible (Tet) system were
      developed. The two components of the Tet system were organized within the vectors
      in a manner that stringently maintains tetracycline-dependent regulation.
      Regulated expression of an indicator gene inserted into the retroviral vectors
      was examined in several different cell types. In infected NIH 3T3 cells, levels
      of induction in the absence of tetracycline were observed to be as much as 336
      fold higher than levels in the presence of tetracycline, which were extremely
      low. Tetracycline-dependent regulation was observed in all other transduced cell
      types and ranged from 24- to 127-fold. The generation of retroviral vectors
      containing regulatory elements that allow for the regulated expression of
      heterologous genes and that have the ability to infect virtually all dividing
      target cells should greatly facilitate the biochemical and genetic examination of
      a broad range of genes. Moreover, these inducible retroviral vectors should prove
      useful in gene therapy applications.

PMID- 8523583
TI  - Transcription start sites downstream of the Epstein-Barr virus (EBV) Fp promoter
      in early-passage Burkitt lymphoma cells define a fourth promoter for expression
      of the EBV EBNA-1 protein.
AB  - In Epstein-Barr virus (EBV)-transformed B lymphoblastoid and many Burkitt
      lymphoma cell lines, the EBV EBNA-1 protein is one of six viral nuclear antigens
      expressed from a common transcription unit under the control of one of two
      promoters, Wp or Cp. In contrast, EBNA-1 is the only EBV nuclear antigen
      expressed in Burkitt and other EBV-positive tumors. We previously identified a
      promoter of EBNA-1 transcription, designated Fp, in early-passage Mutu Burkitt
      tumor cells, and this promoter is also active in long-term Mutu and Akata Burkitt
      cell lines which maintain the exclusive expression of EBNA-1 characteristic of
      the tumor. However, transcription initiation within Fp reporter gene plasmids in
      EBV-negative cells occurs at positions 100 to 200 bases downstream of the Fp
      start site in the BamHI-Q restriction fragment. Here we demonstrate that
      transcription initiation within newly established Burkitt lymphoma cell lines is
      consistent with the transcription initiation we observed in reporter plasmids.
      Furthermore, previous observations of transcription from Fp to generate EBNA-1
      transcripts can be attributed to lytic-cycle gene expression. These data, in
      conjunction with our previous characterization of promoter regulatory elements,
      define a fourth EBNA-1 promoter, Qp, that is active in latently infected Burkitt
      tumor cells.

PMID- 8523584
TI  - Kinetic analysis of intravirion reverse transcription in the blood plasma of
      human immunodeficiency virus type 1-infected individuals: direct assessment of
      resistance to reverse transcriptase inhibitors in vivo.
AB  - Intravirion reverse transcripts have been identified in the blood plasma of human
      immunodeficiency virus type 1 (HIV-1)-infected individuals. In the present
      studies, the kinetic processes of intravirion HIV-1 reverse transcription, in the
      blood plasma of HIV-1-infected persons treated with nevirapine, were
      investigated. Nevirapine is a nonnucleoside inhibitor of reverse transcriptase
      (RT) which decreases the level of HIV-1 viral particles in the blood plasma of
      infected individuals. By analyzing HIV-1 virions at different time points prior
      to and after initiation of nevirapine therapy in vivo, the levels of intravirion
      reverse transcripts have been demonstrated to be dramatically susceptible to this
      anti-RT agent, out of proportion to effects on plasma virion load. The
      intravirion reverse transcripts were also documented to rebound to the
      pretreatment levels, concomitant with the development of resistant viral mutants.
      In addition, the infectivity of HIV-1 virions dramatically decreased after
      nevirapine treatment, further indicating that the effects of this anti-RT agent
      begin within the cell-free virions. Since the levels of intravirion reverse
      transcripts were altered according to the susceptibility or resistance of the HIV
      1 RT enzyme to this inhibitor, these data demonstrate that the formation of
      intravirion reverse transcripts is a dynamic process in vivo. Moreover, because
      the alteration in ratios between intravirion HIV-1 reverse transcripts and viral
      genomic RNA directly reflects the efficiency of reverse transcription, we propose
      that the determination of these ratios in the blood plasma of HIV-1-positive
      patients may be a useful and, most importantly, a direct assay to monitor the
      efficacy of anti-RT agents in vivo.

PMID- 8523585
TI  - Sequence variability of Borna disease virus open reading frame II found in human
      peripheral blood mononuclear cells.
AB  - A cDNA fragment of the Borna disease virus (BDV) open reading frame II (ORF-II),
      which encodes a 24-kDa phosphoprotein (p24 [P protein]), was amplified from total
      RNA of peripheral blood mononuclear cells (PBMC) from three psychiatric
      inpatients. The amplified cDNA fragments were cloned, sequenced, and analyzed. A
      total of 15 clones, 5 from each patient, were studied. Intrapatient divergencies
      of the BDV ORF-II nucleotide sequence were 4.2 to 7.3%, 4.8 to 7.3%, and 2.8 to
      7.1% for the three patients, leading to differences of 7.7 to 14.5%, 10.3 to
      17.1%, and 6.0 to 16.2%, respectively, in the deduced amino acid sequence for BDV
      p24. Interpatient divergencies among the 15 clones were 5.9 to 12.7% at the
      nucleotide level and 12.8 to 28.2% at the amino acid level. Thus, in p24, BDV in
      human PBMC of the patients undergoes mutation at high rates in vivo.
      Additionally, we found that the nucleotide sequence of the 15 human BDV ORF-II
      cDNA clones differed from those of the horse strains V and He/80-1 by 4.2 to
      9.3%. However, comparison of the consensus amino acid sequence deduced from the
      15 human clones with those of the horse strains revealed no human-specific amino
      acid residue, suggesting that the BDV infecting humans may be related to that
      infecting horses.

PMID- 8523586
TI  - Hepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf
      independent pathway.
AB  - In this study, we characterized the molecular events involved in the activation
      of the ubiquitous transcription factor NF-kappa B by the viral transactivator pX.
      pX expression in HeLa cells determines a manyfold increase in NF-kappa B
      dependent transcription, which is associated with an increase in p50/p65
      heterodimer DNA-binding activity. Since the I kappa B-alpha inhibitory subunit
      proteolytic degradation, which follows its phosphorylation/modification, is a key
      event in NF-kappa B activation by different stimuli (such as growth factors,
      phorbol esters, tumor necrosis factor, UV irradiation, and oxygen radicals), we
      investigated pX effects on I kappa B-alpha, as well as the possible involvement
      of known signalling pathways in pX-induced NF-kappa B-dependent transcription. We
      observed that although pX had no direct effect on p50 or p65, it was able to
      restore the I kappa B-alpha-suppressed p50/p65 activity. More directly, the
      stable expression of pX in HeLa cells resulted in reduced levels of I kappa B
      alpha in the cytoplasm. Pretreatment of the cells with H7, calphostin C,
      tyrphostin 25, or N-acetylcysteine did not impair the effects of pX on NF-kappa
      B, thus ruling out the involvement of protein kinase C, tyrosine kinases, and
      oxygen radicals. Finally, while most of the known NF-kappa B-activating agents
      converge on Raf-1 protein kinase, when Raf-1 activity is blocked by
      overexpression of a dominant negative mutant, the effects of pX on NF-kappa B are
      not impaired. Thus, we suggest that although pX is able to activate the Ras/Raf-1
      signalling pathway, it triggers NF-kappa B activation by an as yet unidentified
      Raf-1-independent pathway.

PMID- 8523587
TI  - The antiviral state induced by alpha interferon and gamma interferon requires
      transcriptionally active Stat1 protein.
AB  - Both of the latent transcription factors activated by alpha interferon or gamma
      interferon contain the Stat1 protein. The role of Stat1 in virus interference
      mediated by interferons was directly examined by using cultured cells expressing
      Stat1 protein and its variants. In the absence of Stat1, no antiviral state is
      established. Full complementation of the antiviral state requires full-length
      Stat1 which is phosphorylated on both tyrosine 701 and serine 727. The closely
      related signal transducer and activator of transcription protein Stat3 cannot
      substitute for the antiviral properties of Stat1.

PMID- 8523588
TI  - Conserved sequences in the carboxyl terminus of integrase that are essential for
      human immunodeficiency virus type 1 replication.
AB  - We have previously identified a residue in the carboxyl terminus of human
      immunodeficiency virus type 1 integrase (HIV-1 IN), W-235, the requirement for
      which is only revealed in viral assays for integrase function (P. M. Cannon, W.
      Wilson, E. Byles, S. M. Kingsman, and A. J. Kingsman, J. Virol. 68:4768-4775,
      1994). Our further analysis of this region of retroviral IN has now identified
      several sequence motifs which are conserved in all the retroviruses we examined,
      apart from human spumaretrovirus. We have made mutations within these motifs in
      HIV-1 IN and examined their phenotypes when reintroduced into an infectious
      proviral clone. The deleterious effects of several of these mutations demonstrate
      the importance of these regions for IN function in vivo. We observed a further
      discrepancy, at a motif that is only conserved in the lentiviruses, in the
      ability of mutants to function in in vitro and in vivo assays. Substitutions both
      in this region and at W-235 abolish HIV-1 infectivity but do not affect particle
      production, morphology, reverse transcription, or nuclear import in T-cell lines.
      Taken together with the in vitro data suggesting that neither of these residues
      is directly involved in the catalytic reactions of IN, it seems likely that we
      have identified regions of IN that are essential for interactions with other
      components of the integration machinery.

PMID- 8523589
TI  - Phosphorylation and nuclear localization of the varicella-zoster virus gene 63
      protein.
AB  - The protein encoded by varicella-zoster virus open reading frame 63 and carboxy
      terminal deletions of the same were expressed either as fusion proteins at the
      carboxy terminus of the maltose-binding protein in Escherichia coli or
      independently in transfected mammalian cells. The truncations contained amino
      acids 1 to 142 (63 delta N) or 1 to 210 (63 delta K) of the complete 278-amino
      acid primary sequence. Recombinant casein kinase II phosphorylated the 63F and 63
      delta KF fusion proteins in vitro but did not phosphorylate the 63 delta NF
      fusion protein, implying that phosphorylation occurred between amino acids 142
      and 210. Immunoprecipitation of 35S- or 32P-labelled extracts of cells
      transfected with plasmids expressing 63, 63 delta N, or 63 delta K also indicated
      that in situ phosphorylation most likely occurred between amino acids 142 and
      210. These combined results suggest that casein kinase II plays a significant
      role in the phosphorylation of the varicella-zoster virus 63 protein. Indirect
      immunofluorescence of transfected cells indicated nuclear localization of the 63
      protein and cytoplasmic localization of 63 delta K and 63 delta N, implying a
      requirement for sequences between amino acids 210 and 278 for efficient nuclear
      localization.

PMID- 8523590
TI  - bcl-2 alters influenza virus yield, spread, and hemagglutinin glycosylation.
AB  - We previously demonstrated that expression of bcl-2 in Madin-Darby canine kidney
      (MDCK) cells blocks influenza virus-induced apoptosis and DNA fragmentation. We
      show here that expression of bcl-2 also reduces the level of infectious virus
      production and the spread of virus in MDCK cell cultures infected at a low
      multiplicity of infection. This effect is associated with modified glycosylation
      of the hemagglutinin protein.

PMID- 8523591
TI  - Specific binding of human immunodeficiency virus type 1 (HIV-1) Gag-derived
      proteins to a 5' HIV-1 genomic RNA sequence.
AB  - We developed an in vitro binding assay to study the specific interaction between
      human immunodeficiency virus type 1 (HIV-1) RNA and the Gag polyprotein. Binding
      of the in vitro-expressed protein to in vitro-transcribed RNA was determined by
      altered migration of the protein in polyacrylamide gels. We found that a Gag
      precursor lacking the matrix domain bound specifically to HIV-1 RNA, while
      deletion of both matrix and capsid domains diminished the specificity of binding.
      Among several regions of HIV-1 RNA tested, strongest binding was seen with the 5'
      most 261 nucleotides, while antisense RNA from the same region did not bind.

PMID- 8523592
TI  - Monoclonal antibodies to reovirus sigma 1 and mu 1 proteins inhibit chromium
      release from mouse L cells.
AB  - Reovirus intermediate subviral particles (ISVPs) but not intact virions or cores
      have been shown to possess the capacity to permeabilize mouse L cells as
      determined by a 51Cr release assay. We used monoclonal antibodies (MAbs) directed
      against proteins exposed on the ISVP surface (sigma 1, mu 1, and lambda 2) to
      probe the role(s) of these proteins in membrane interaction and penetration. One
      sigma 1-specific MAb (MAb-G5) and two mu 1-specific MAbs (MAb-10H2 and MAb-8H6)
      inhibited reovirus-induced 51Cr release when added pre- or post-ISVP attachment
      to L cells. MAb-G5 inhibits 51Cr release by interfering with ISVP attachment (via
      sigma 1) to L-cell receptor sites. The mu 1-specific MAbs (MAb-10H2 and MAb-8H6)
      inhibit 51Cr release by interfering with an undefined post-L-cell-attachment
      event that involves bivalent binding of the mu 1-specific MAbs to an epitope
      located in a central region of the mu 1 protein.

PMID- 8523593
TI  - Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through
      DNA vaccination of rhesus monkeys.
AB  - In view of the growing evidence that virus-specific cytotoxic T lymphocytes (CTL)
      play an important role in containing the early spread of human immunodeficiency
      virus type 1 (HIV-1) in infected individuals, novel vaccine strategies capable of
      eliciting HIV-1-specific CTL are being pursued in attempts to create an effective
      AIDS vaccine. We have used the simian immunodeficiency virus of macaques
      (SIVmac)/rhesus monkey model to explore the induction of AIDS virus-specific CTL
      responses by DNA vaccination. We found that the inoculation of rhesus monkeys
      with plasmid DNA encoding SIVmac Env and Gag elicited a persisting SIVmac
      specific memory CTL response. These CTL were CD8+ and major histocompatibility
      complex class I restricted. These studies provide evidence for the potential
      utility of DNA inoculation as an approach to an HIV-1 vaccine.

PMID- 8523594
TI  - Induction of susceptibility to tumor necrosis factor by E1A is dependent on
      binding to either p300 or p105-Rb and induction of DNA synthesis.
AB  - The introduction of the adenovirus early region 1A (E1A) gene products into
      normal cells sensitizes these cells to the cytotoxic effects of tumor necrosis
      factor (TNF). Previous studies have shown that the region of E1A responsible for
      susceptibility is CR1, a conserved region within E1A which binds the cellular
      proteins p300 and p105-Rb at nonoverlapping sites. Binding of these and other
      cellular proteins by E1A results in the induction of E1A-associated activities
      such as transformation, immortalization, DNA synthesis, and apoptosis. To
      investigate the mechanism by which E1A induces susceptibility to TNF, the NIH 3T3
      mouse fibroblast cell line was infected with viruses containing mutations within
      E1A which abrogate binding of some or all of the cellular proteins to E1A. The
      results show that TNF susceptibility is induced by E1A binding to either p300 or
      p105-Rb. E1A mutants that bind neither p300 nor p105-Rb do not induce
      susceptibility to TNF. Experiments with stable cell lines created by transfection
      with either wild-type or mutant E1A lead to these same conclusions. In addition,
      a correlation between induction of DNA synthesis and induction of TNF sensitivity
      is seen. Only viruses which induce DNA synthesis can induce TNF sensitivity.
      Those viruses which do not induce DNA synthesis also do not induce TNF
      sensitivity. These data suggest that the mechanisms underlying induction of
      susceptibility to TNF by E1A are intimately connected to E1A's capacity to
      override cell cycle controls.

PMID- 8523595
TI  - Human cytomegalovirus clinical isolates carry at least 19 genes not found in
      laboratory strains.
AB  - Nucleotide sequence comparisons were performed on a highly heterogeneous region
      of three human cytomegalovirus strains, Toledo, Towne, and AD169. The low
      passage, virulent Toledo genome contained a DNA segment of approximately 13 kbp
      that was not found in the Towne genome and a segment of approximately 15 kbp that
      was not found in the AD169 genome. The Towne strain contained approximately 4.7
      kbp of DNA that was absent from the AD169 genome, and only about half of this
      segment was present, arranged in an inverted orientation, in the Toledo genome.
      These additional sequences were located at the unique long (UL)/b' (IRL) boundary
      within the L component of the viral genome. A region representing nucleotides
      175082 to 178221 of the AD169 genome was conserved in all three strains; however,
      substantial reduction in the size of the adjacent b' sequence was found. The
      additional DNA segment within the Toledo genome contained 19 open reading frames
      not present in the AD169 genome. The additional DNA segment within the Towne
      genome contained four new open reading frames, only one of which shared homology
      with the Toledo genome. This comparison was extended to five additional clinical
      isolates, and the additional Toledo sequence was conserved in all. These findings
      reveal a dramatic level of genome sequence complexity that may explain the
      differences that these strains exhibit in virulence and tissue tropism. Although
      the additional sequences have not altered the predicted size of the viral genome
      (230 to 235 kbp), a total of 22 new open reading frames (denoted UL133 to UL154),
      many of which have sequence characteristics of glycoproteins, are now defined as
      cytomegalovirus specific. Our work suggests that wild-type virus carries more
      than 220 genes, some of which are lost by large-scale deletion and rearrangement
      of the UL/b' region during laboratory passage.

PMID- 8523596
TI  - The carboxyl terminus of the murine MyD116 gene substitutes for the corresponding
      domain of the gamma(1)34.5 gene of herpes simplex virus to preclude the premature
      shutoff of total protein synthesis in infected human cells.
AB  - The herpes simplex virus 1 mutants from which both copies of the gamma(1)34.5
      gene had been deleted trigger total shutoff of protein synthesis in human
      neuroblastoma cells and human foreskin fibroblasts but not in African green
      monkey (Vero) cells. The carboxyl-terminal 64 amino acids of gamma(1)34.5 are
      homologous to the corresponding domain of MyD116, a murine myeloid
      differentiation primary responsive gene. The carboxyl-terminal domain of
      gamma(1)34.5 is required to preclude the shutoff of protein synthesis (J. Chou
      and B. Roizman, Proc. Natl. Acad. Sci. USA 91:5247-5251, 1994). We report that in
      frame substitution of the carboxyl terminus of gamma(1)34.5 with the
      corresponding domain of MyD116 in the context of the viral genome restored the
      ability of gamma(1)34.5 to preclude premature shutoff of protein synthesis in
      both neuroblastoma cells and in human foreskin fibroblasts. The results suggest
      that (i) in the course of its evolution, the virus "borrowed" a gene fragment to
      preclude a cell response to infection and (ii) the carboxyl terminus of MyD116
      and its family of genes known as GADD34 may have a similar function(s) in cells
      stressed by growth arrest, DNA damage, and differentiation and in herpes simplex
      virus infection.

PMID- 8523598
TI  - From the vineyard--reflections and perspectives.

PMID- 8523597
TI  - Regulation of a human cytomegalovirus immediate-early gene (US3) by a silencer
      enhancer combination.
AB  - The US3 open reading frame of human cytomegalovirus (HCMV) is transcribed at
      immediate-early (IE) times after infection. Upstream of the US3 promoter, between
      -84 and -259 bp relative to the transcription start site, there are five copies
      of an 18-bp repeat, referred to as 5R2. Between -340 and -560 bp there are seven
      copies of a 10-bp dyad repeat, referred to as 7R1. We investigated the roles of
      these repeats in transcription from the US3 promoter in human foreskin fibroblast
      or HeLa cells. In transient transfection assays, the region containing 5R2 up
      regulated transcription and was responsive to the p65 subunit of NF-kappa B. The
      DNA region containing 7R1 down-regulated transcription from either the US3
      promoter or a heterologous promoter in a position- and orientation-independent
      manner. Mutational analysis and transient transfections indicated that DNA
      containing the 10-bp dyad or one-half of the dyad was sufficient to cause
      repression of downstream gene expression. DNA probes containing one or more
      copies of the pentanucleotide sequence TGTCG specifically bound cellular
      proteins, as demonstrated by electrophoretic mobility shift assays and cold
      competition electrophoretic mobility shift assays. Two different DNA-protein
      complexes were detected with DNA probes containing one or two copies of the
      pentanucleotide. In HCMV-infected cell nuclear extracts, one of the DNA-protein
      complexes was present in amounts inversely proportional to the amount of US3
      transcription. Its formation was affected by dephosphorylation of the DNA-binding
      protein(s). Transient dephosphorylation of the cellular repressor protein may
      occur during HCMV infection. Repression of US3 transcription may relate to the
      number of pentanucleotides and the cellular proteins that bind to it. Twenty-one
      copies of a TRTCG motif (R = purine) were found clustered upstream of the US3
      gene and also in the modulator upstream of the HCMV IE1 and IE2 genes.

PMID- 8523599
TI  - Impact of clinical pathways on hospital costs and early outcome after major
      vascular surgery.
AB  - PURPOSE: The purpose of this study was to determine whether major vascular
      surgery could be performed safely and with significant hospital cost savings by
      decreasing length of stay and implementation of vascular clinical pathways.
      METHODS: Morbidity, mortality, readmission rates, same-day admissions, length of
      stay, and hospital costs were compared between patients who were electively
      admitted between September 1, 1992, and August 30, 1993 (group 1), and January 1
      to December 31, 1994 (group 2), for extracranial, infrarenal abdominal aortic,
      and lower extremity arterial surgery. For group 2 patients, vascular critical
      pathways were instituted, a dedicated vascular ward was established, and
      outpatient preoperative arteriography and anesthesiology-cardiology evaluations
      were performed. Length-of-stay goals were 1 day for extracranial, 5 days for
      aortic, and 2 to 5 days for lower extremity surgery. Emergency admissions,
      inpatients referred for vascular surgery, patients transferred from other
      hospitals, and patients who required prolonged preoperative treatment were
      excluded. RESULTS: With this strategy same-day admissions were significantly
      increased (80% [145/177] vs 6.2% [9/145]) (p < 0.0001), and average length of
      stay was significantly decreased (3.8 vs 8.8 days) (p < 0.0001) in group 2 versus
      group 1, respectively. There were no significant differences between group 1 and
      group 2 in terms of overall mortality rate (2.1% [3/145] vs 2.3% [4/177]),
      cardiac (3.4% [5/145] vs 4.0% [7/177]), pulmonary (4.1% [6/145] vs 1.7% [3/177]),
      or neurologic (1.4% [2/145] vs 0% [0/177]) complications, or readmission within
      30 days (11.3% [16/142] vs 9.2% [16/173]) (p > 0.05). There were also no
      differences in morbidity or mortality rates when each type of surgery was
      compared. Annual hospital cost savings totalled $1,267,445. CONCLUSION: Same-day
      admission and early hospital discharge for patients undergoing elective major
      vascular surgery can result in significant hospital cost savings without apparent
      increase in morbidity or mortality rates.

PMID- 8523600
TI  - Inhibition of nitric oxide synthase attenuates primed microvascular permeability
      in the in vivo microcirculation.
AB  - PURPOSE: Changes in microvascular permeability play a critical role in the
      inflammatory sequence of tissue injury leading to leakage of proteins and
      subsequent edema. Primed responses induced by topical applications of platelet
      activating factor (PAF) and histamine greatly increase microvascular permeability
      and mimic inflammation. We assessed the role of nitric oxide (NO) by use of 1-NG
      monomethyl arginine (1-NMMA, a NO synthase inhibitor), on the primed
      microvascular permeability. We also explored the role of mast cells and a
      leukocyte adhesion complex by use of cromolyn sodium and 1B6 (a monoclonal
      antibody), respectively. METHODS: Forty anesthetized hamsters were separated into
      five groups: group 1 (n = 5) received no intervention; group 2 (n = 5) received
      topical 10(-9) mol/L PAF and 10(-6) mol/L histamine at a 5-minute interval; group
      3 (n = 5 at each dose) received PAF/histamine and 1-NMMA (at 10(-5) mol/L or 10(
      6) mol/L); group 4 (n = 5 at each dose) received cromolyn sodium plus
      PAF/histamine; group 5 (n = 5) received 1B6 plus PAF/histamine. We examined the
      cheek pouch with intravital videomicroscopy under fluorescent epiillumination. We
      quantified microvascular permeability to fluorescein isothiocyanate-dextran 150
      with computer-assisted images analysis on the basis of integrated optical
      intensity (IOI) measurements. RESULTS: The mean (+/- SEM) IOI of the control
      group was 8.7 +/- 5.2, whereas the group primed with PAF and histamine was 62.4
      +/- 10.8. The 1-NMMA (10(-5) mol/L and 10(-6) mol/L) abolished the changes in
      microvascular permeability (p < 0.05) yielding IOI values of 8.0 +/- 1.6 and 10.9
      +/- 2.8, respectively. Cromolyn sodium and 1B6 did not significantly attenuate
      the primed response to PAF and histamine. CONCLUSION: Inhibition of NO synthase
      attenuates primed macromolecular extravasation in vivo. Our results indicate that
      NO is involved in the primed reaction of PAF and histamine, causing increases in
      microvascular permeability. Our study suggests a role for NO in the
      microcirculatory changes observed in ischemia-reperfusion injury and shock.

PMID- 8523601
TI  - Outpatient echocardiography as a predictor of perioperative cardiac morbidity
      after peripheral vascular surgical procedures.
AB  - PURPOSE: A variety of preoperative provocative tests have been used to define the
      risk of cardiac morbidity and mortality after peripheral vascular procedures,
      including dipyridamole myocardial scintigraphy and dobutamine stress
      echocardiography. Although highly sensitive, these tests are time-consuming and
      associated with significant expense. We investigated outpatient echocardiography
      as a less resource-intensive means of assessing cardiac risk with operation.
      METHODS: Over a 2-year period 250 consecutive patients underwent outpatient
      transthoracic echocardiography before elective peripheral vascular operation was
      performed. The accuracy of the Goldman, Detsky, and the American Society of
      Anesthesiologists' Physical Status Classification clinical indexes of cardiac
      risk were assessed with regard to the development of cardiac complications such
      as unstable angina, myocardial infarction, life-threatening ventricular
      arrhythmias, severe congestive heart failure, and cardiogenic shock. The accuracy
      of echocardiographically determined left ventricular ejection fraction was
      determined at threshold values between 20% and 60%. RESULTS: Perioperative
      cardiac events developed in 23 (9.2%) of the patients, and nine (3.6%) of the
      patients died as a result of these complications. Clinical indexes lacked
      sensitivity in the preoperative prediction of cardiac complications. Receiver
      operating curve analysis defined a left ventricular ejection fraction of less
      than 50% as an appropriate threshold for defining patients at high risk, with a
      sensitivity of 78% and a specificity of 81% in the identification of patients who
      had cardiac morbidity. The positive predictive value was 27%, and the negative
      predictive value was 97%. The economic impact of outpatient echocardiography was
      well below that of dipyridamole myocardial scintigraphy or dobutamine stress
      echocardiography. CONCLUSIONS: Outpatient echocardiography appears to offer a
      cost-efficient compromise between clinical criteria alone and provocative cardiac
      testing such as dipyridamole myocardial scintigraphy and dobutamine stress
      echocardiography in the preoperative screening of patients undergoing peripheral
      vascular surgical procedures.

PMID- 8523602
TI  - Differences in early versus late extracavitary arterial graft infections.
AB  - PURPOSE: The purpose of this report was to determine differences in presentation,
      bacteriology, management, and outcome of early (EGIs) versus late extracavitary
      arterial graft infections (LGIs). METHODS: Between July 1, 1979, and June 30,
      1994, we treated 141 patients with infected extracavitary arterial grafts (112
      prosthetic, 29 vein) with selective partial or complete graft preservation.
      RESULTS: A total of 99 (70%) EGIs (< 2 months) and 42 (30%) LGIs (4 to 96 months)
      were involved. The hospital mortality rate was 14% (20 of 141), and the
      amputation rate in survivors was 13% (16 of 121). No significant difference in
      mortality (16% [16 of 99] vs 10% (4 of 42]) or limb loss (16% [13 of 83] vs 8% [3
      of 38]) was seen between EGIs and LGIs, respectively (p > 0.05). Patients with
      EGIs were as likely to have a disrupted anastomosis (17% [17 of 99] vs 21% [9 of
      42]) or systemic sepsis (4% [4 of 99] vs 4% [2 of 42]) as patients with LGIs,
      respectively (p > 0.05). Patients with EGIs were more likely to have patent,
      intact grafts and to be treated by complete graft preservation (61% [61 of 99] vs
      26% [11 of 42]) (p = 0.0001). In comparison, patients with LGIs were more likely
      to have occluded grafts and to require subtotal graft excision (48% [20 of 42] vs
      18% [18 of 99]) (p = 0.0001). Surviving patients with EGIs treated by complete
      graft preservation were more likely to have successful healing of their wounds
      after long-term follow-up (average 3 years) than patients with LGIs (79% [41 of
      52] vs 40% [4 of 10], respectively) (p = 0.03). The pathogens cultured from
      wounds of EGIs versus LGIs were pure gram-positive bacteria in 49 (49%) versus 19
      (46%), pure gram-negatives in 18 (18%) versus 11 (26%), and both types in 33
      (33%) versus 12 (28%) (p > 0.05). CONCLUSION: Complete graft preservation can be
      attempted more frequently and is more likely to be successful in EGIs than in
      LGIs. No difference in bacteriology was seen between the two groups. Graft
      preserving treatment can be successful but should only be cautiously attempted in
      patients with late extracavitary arterial graft infections.

PMID- 8523603
TI  - Aortic aneurysm in heart transplant recipients.
AB  - PURPOSE: The purpose of this study was to define the clinical features of aortic
      aneurysms occurring in heart transplant recipients. METHODS: Among the 734
      patients who have undergone heart transplantation at our institution over the
      last 14 years, we have identified 12 patients (1.6% incidence) with aortic
      aneurysms (9 infrarenal, 3 thoracoabdominal), making this the largest reported
      series of aortic aneurysms (AA) in heart transplant recipients. RESULTS: For nine
      of the 12 patients with AA (75%), the indication for transplantation was ischemic
      cardiomyopathy. This indication accounted for only 42% of the overall
      transplantation group; our data therefore show that the risk of infrarenal AA
      disease was higher for patients who underwent transplantation for ischemic
      cardiomyopathy than for other indications (p = 0.02). In two of the patients with
      thoracoabdominal AA, chronic dissection was identified as the specific AA cause,
      whereas all of the other patients in the study had nonspecific "atherosclerotic"
      AAs. All 12 patients were symptom free at the time of initial discovery of the
      AAs. Two of the patients with infrarenal AA were diagnosed with AAs before
      transplantation; for the seven remaining patients with infrarenal AAs, the mean
      time between transplantation and AA discovery was 5.0 years (range 1.2 to 11.8
      years). Serial radiologic studies allowed us to determine the AA expansion rate
      in seven of the 12 patients. This rate varied from 0 to 2.53 cm/yr (mean 1.20
      cm/yr; 1.0 cm/yr for infrarenal AA alone). Five patients with infrarenal AA
      underwent AA repair as the initial treatment. Three others underwent repair after
      their AAs significantly expanded under observation. Mean AA diameter at the time
      of repair was 6.9 cm. All three patients with thoracoabdominal AAs died of acute
      AA rupture before resection could be done, despite their initial asymptomatic
      state. AA diameters at time of rupture were 3.5, 6.0, and 11 cm. All of the eight
      patients with AA treated with surgery are alive and well (median follow-up 18
      months). The only complication was acute heart transplant rejection, which
      occurred 11 days after AA repair in one patient. CONCLUSIONS: Our data suggest
      that AA occurrence is more likely in patients who undergo heart transplantation
      for ischemic heart disease than for other indications. Careful serial radiologic
      surveillance is warranted in any heart transplant patient with an AA, because of
      the apparent potential for more rapid AA expansion in this patient population
      than in patients who do not undergo transplantation. We conclude that early
      repair of infrarenal AA is indicated because excellent operative results and low
      morbidity rates can be achieved. An aggressive approach to thoracoabdominal AAs
      in this group may also be appropriate because of the apparent propensity to
      lethal rupture, sometimes at relatively small AA size.

PMID- 8523604
TI  - Determination of sixty percent or greater carotid artery stenosis by duplex
      Doppler ultrasonography.
AB  - PURPOSE: The Asymptomatic Carotid Atherosclerosis Study, demonstrating the
      benefit of carotid endarterectomy for symptom-free patients with 60% or greater
      carotid artery stenosis, has given rise to the need for development of screening
      parameters for detection of these lesions. Traditional duplex categories (50% to
      79%, 80% to 99%) are not applicable. We sought to develop duplex criteria for
      determination of 60% or greater carotid artery stenosis by comparison with
      arteriography. METHODS: The duplex scans and arteriograms of 110 patients (210
      carotid arteries), obtained within 1 month of each other, were reviewed by
      blinded readers. Arteriographic stenosis was determined by the method of the
      Asymptomatic Carotid Atherosclerosis Study. Duplex measurements of peak systolic
      velocity (PSV) and end-diastolic velocity (EDV) were recorded, and ratios of
      velocities in the internal and common carotid arteries (ICA, CCA) were
      calculated. Sensitivity, specificity, positive and negative predictive values
      (PPV, NPV), and accuracy were determined, and receiver-operator characteristic
      curves were generated. RESULTS: Interobserver agreement for measurement of
      arteriographic stenosis was "almost perfect" (kappa = 0.86). The criteria
      determined for detection of 60% or greater stenosis were as follows: PSVICA > 170
      cm/sec (sensitivity 98%, specificity 87%, PPV 88%, NPV 98%, accuracy 92%), EDVICA
      > 40 cm/sec (sensitivity 97%, specificity 52%, PPV 86%, NPV 86%, accuracy 86%),
      PSVICA/PSVCCA > 2.0 (sensitivity 97%, specificity 73%, PPV 78%, NPV 96%, accuracy
      76%), EDVICA/EDVCCA > 2.4 (sensitivity 100%, specificity 80%, PPV 88%, NPV 100%,
      accuracy 88%). If all of the above criteria were met, 100% accuracy was achieved.
      CONCLUSION: It is concluded that 60% or greater carotid artery stenosis can be
      reliably determined by duplex criteria. The use of receiver-operator
      characteristic curves allows the individualization of duplex criteria appropriate
      to specific clinical situations of patient screening for lesions (high
      sensitivity and NPV) or use as a sole preoperative imaging modality (high PPV).
      Individual vascular laboratories must validate their own results.

PMID- 8523605
TI  - Carotid endarterectomy in asymptomatic patients--is contrast angiography
      necessary? A morbidity analysis.
AB  - PURPOSE: Findings from the Asymptomatic Carotid Atherosclerosis Study (ACAS)
      indicate that carotid endarterectomy can be beneficial in symptom-free patients
      with 60% to 99% carotid artery stenosis. However, patients in ACAS who underwent
      contrast angiography (CA) before carotid endarterectomy were exposed to an
      additional 1.2% risk of stroke. METHODS: We used the methods of decision analysis
      to assess whether the overall 5-year stroke risk in symptom-free patients with
      suspected carotid artery disease can be reduced by preoperative imaging with
      magnetic resonance angiography (MRA) or duplex ultrasonography (DU). We compared
      four strategies for the preoperative evaluation of carotid artery stenosis in
      symptom-free patients: 1) CA alone, 2) MRA alone, 3) DU alone, and 4) MRA and DU
      with CA when the results of these tests disagree. Accuracies of MRA and DU were
      estimated from 81 patients exposed to all three procedures; stroke risks for
      patients with 60% to 99% carotid artery stenosis were obtained from ACAS.
      RESULTS: For predicting 60% to 99% carotid stenoses, sensitivity and specificity
      for noninvasive tests, optimized to reduce morbidity, were as follows: DU (0.96,
      0.66), MRA (1.00, 0.76), DU/MRA (1.00, 0.86; 26% would require CA). The 5-year
      stroke risk of these four strategies in order of decreasing benefit was MRA,
      6.17%; MRA/DU, 6.34%; DU, 6.35%; and CA, 7.12%. In sensitivity analyses,
      noninvasive tests were advantageous even if the stroke rate with CA diminished to
      0.4%, or if the sensitivity and specificity of noninvasive tests fell to 70%.
      CONCLUSION: The preoperative use of noninvasive tests resulted in a lower 5-year
      stroke risk compared with CA in symptom-free patients with suspected carotid
      artery stenosis.

PMID- 8523606
TI  - Carotid-axillary artery bypass: a ten-year experience.
AB  - PURPOSE: The purpose of this study was to review our 10-year experience with
      carotid-axillary artery bypass in the treatment of occlusive lesions of the
      proximal subclavian artery. METHODS: Our 10-year experience with 26 carotid
      axillary bypasses for occlusive disease of the subclavian artery was reviewed
      retrospectively. The review focused on the indication for the operation, the
      surgical technique used, and the development of immediate and late postoperative
      complications. Long-term bypass graft patency and clinical success were
      determined on the basis of information gleaned from the office records of all
      patients. Only three patients were lost to follow-up at 12, 36, and 38 months.
      RESULTS: There were no operative deaths. Two patients had small cervical wound
      hematomas, and two others experienced transient symptoms of brachial plexus
      irritation, which subsided spontaneously. Permanent nerve or lymphatic
      complications did not occur. In a mean follow-up of 47 months, carotid-axillary
      bypass graft patency was 96%, and 88% of the patients enjoyed symptom-free
      sustained clinical success. CONCLUSIONS: This retrospective review demonstrates
      that a carotid-axillary bypass constructed with ringed synthetic graft material
      tunneled under the clavicle performs well and can be considered a reasonable
      alternative to the more standard carotid-subclavian bypass for the same
      indications.

PMID- 8523607
TI  - Expanded polytetrafluoroethylene patch angioplasty in carotid endarterectomy.
AB  - PURPOSE: This study retrospectively reviewed the experience with expanded
      polytetrafluoroethylene (ePTFE) patches for carotid endarterectomy in 924
      consecutive procedures (753 patients) during a 17-year period. METHODS: The
      records of all patients who underwent ePTFE patch angioplasty for carotid artery
      stenosis performed by one surgeon were reviewed. The criterion for surgery was
      stenosis of 80% or greater. Follow-up by use of noninvasive methods was done by 6
      months after operation the first year and annually thereafter. Recurrent stenosis
      was confirmed with angiography. Life-table analysis was used to estimate the risk
      of restenosis. RESULTS: Early morbidity and mortality included six deaths (0.6%),
      seven nonfatal strokes (0.9%), and 19 hemorrhages. Two postoperative infections
      occurred. There were no important aneurysmal dilations and no late hemorrhages.
      With a mean follow-up of 41.4 months (range 0 to 197), recurrent stenosis
      necessitating reoperation developed in 28 patients (3.7%). There were two late
      strokes. Life-table analysis indicated a 89% probability of freedom from stenosis
      at 120 months. CONCLUSIONS: In cases in which the decision to perform patch
      angioplasty is made at surgery, an ePTFE patch is an excellent alternative to
      autogenous saphenous vein, with a low rate of recurrences requiring operation and
      acceptable rates of perioperative and postoperative morbidity and mortality.

PMID- 8523608
TI  - L-type calcium channel blockers modulate the microvascular hyperpermeability
      induced by platelet-activating factor in vivo.
AB  - PURPOSE: Platelet-activating factor (PAF) is a potent phospholipid mediator of
      the microvascular dysfunction associated with ischemia-reperfusion injury.
      Because changes in cytosolic-free Ca2+ concentration are essential in PAF
      cellular signaling, we formulated the hypothesis that blockade of Ca2+ entry may
      inhibit the PAF-induced microvascular dysfunction. METHODS: To investigate this
      hypothesis two L-type calcium channel blockers, verapamil and nifedipine, were
      applied to the hamster cheek pouch before the topical PAF challenge was
      undertaken. Permeability was assessed by measurement of the plasma clearance of
      fluorescein isothiocyanate dextran, 150,000 mol wt. The arteriolar diameter was
      measured simultaneously to evaluate the effects of L-type calcium channel
      blockers on PAF-induced vasoconstriction. RESULTS: Baseline clearance was 498.7
      +/- 225.0 nl/60 min/gm (mean +/- SE). PAF at 10(-8) mol/L (n = 5) increased
      clearance to 3753.8 +/- 572.8 nl/60 min/gm (p < 0.01). Pretreatment with
      verapamil (2 mg/kg; n = 5) significantly reduced the increase in permeability
      caused by 10(-8) mol/L PAF (1909.1 +/- 620.2 nl/60 min/gm; p < 0.05). Nifedipine
      (5-10(-6) mol/L; n = 5) also significantly attenuated the impact of 10(-8) mol/L
      PAF (2037.2 +/- 427.5 nl/60 min/gm; p < 0.05). Neither verapamil nor nifedipine
      affected PAF-induced vasoconstriction. CONCLUSION: The significant inhibition of
      the increase in permeability by the L-type calcium channel blockers suggests that
      these compounds may be useful in the management of PAF-induced hyperpermeability.

PMID- 8523609
TI  - Retrograde iliofemoral endarterectomy facilitated by balloon angioplasty.
AB  - PURPOSE: The purpose of this study was to explore the feasibility of iliofemoral
      endarterectomy performed through a single groin incision. METHODS: Thirty-two
      patients aged 34 to 75 years (mean age 63.4 years) with a male/female ratio of
      20:12 underwent 36 lower extremity inflow reconstructions from July 1989 to
      September 1994. Surgical indications were for limb-threatening ischemia in 24
      patients and for claudication in eight patients. The procedures were done for
      occlusive disease of the external iliac artery and common femoral artery with
      patients under either spinal (n = 24) or local (n = 12) anesthesia.
      Intraoperative balloon angioplasty with fluoroscopic guidance preceded open
      retrograde iliofemoral endarterectomy. Adjunctive procedures included 18
      profundaplasties, eight femorofemoral, nine femoropopliteal, and one femorotibial
      bypasses. RESULTS: Thirty-three of the 36 cases were initially successful. The
      three failures were in patients with extensive calcification. The mean follow-up
      has been 36.4 months, and the patency rate was 80.5% at 3 and 4 years. The four
      failures noted on follow-up were caused by three common iliac artery stenoses and
      one iliac system occlusion. The former group was successfully treated with
      balloon angioplasty/stent, and the latter patient required an aortofemoral
      bypass. No operative deaths or limb loss occurred in this series. CONCLUSIONS:
      Retrograde iliofemoral endarterectomy facilitated by balloon angioplasty is a
      safe, easy-to-perform, and viable option for patients with combined external
      iliac artery and common femoral artery occlusive disease. Midterm results (36.4
      months) are favorable, and most hemodynamic failures are easy to correct with
      standard endovascular techniques.

PMID- 8523610
TI  - Effect of contralateral severe stenosis or carotid occlusion on duplex criteria
      of ipsilateral stenoses: comparative study of various duplex parameters.
AB  - PURPOSE: This study compares the accuracy of various duplex parameters in grading
      ipsilateral carotid stenoses in patients with contralateral severe stenoses or
      occlusion. METHODS: Four duplex criteria were correlated to arteriography in 356
      carotid arteries in blind fashion: (1) standard criteria: a peak systolic
      frequency (PSF) of the internal carotid artery (ICA) of > or = 4 kHz was used to
      diagnose > or = 50% stenosis; (2) new criteria: a PSF of the ICA of > or = 4.5
      kHz was used; (3) Fujitani criteria: a PSF of the ICA of > 4.5 kHz and an end
      diastolic frequency of < 5.0 kHz was used; (4) internal carotid/common carotid
      artery (ICA/CCA) PSF ratio of > or = 1.5 was used. RESULTS: The standard method
      overestimated 56 (16%) of 356 stenoses in contrast to 3% for the new method (p <
      0.001), and this effect was most evident in the 50% to < 80% stenosis category
      (30%). The Fujitani method underestimated 97 (27%) of 356 stenoses, and the
      ICA/CCA ratio overestimated stenoses in 77 (22%) of 356. The overall exact
      correlation was 94%, 82%, 70%, and 75% for the new, standard, Fujitani, and
      ICA/CCA ratio, respectively. The kappa statistic and corresponding confidence
      intervals for the new method (kappa = 0.923, +/- 0.016) are significantly higher
      (p < 0.001) than those for the standard method (kappa = 0.760, +/- 0.027), the
      Fujitani method (kappa = 0.608, +/- 0.031), and the ICA/CCA ratio method (kappa =
      0.642, +/- 0.051). The overall accuracy in diagnosing > or = 50% ipsilateral
      stenosis in the whole series was 85% for the standard method, 97% for the new
      method, 95% for the Fujitani method, and 81% for the ICA/CCA ratio. The new
      method was superior to the standard and ICA/CCA ratio methods (p < 0.001) and the
      Fujitani method (p = 0.024). CONCLUSIONS: The presence of significant
      contralateral stenosis (> or = 50%) can lead to overestimation of ipsilateral
      stenosis if the standard criteria are used; however, this problem can be avoided
      by using a PSF of the ICA of > or = 4.5 kHz for the diagnosis of > or = 50%
      stenosis.

PMID- 8523611
TI  - Mesoportal bypass: a unique operation for mesenteric hypertension.
AB  - A 47-year-old man was referred for evaluation and treatment of gastrointestinal
      variceal bleeding and possible transjugular intrahepatic portal-systemic
      shunting. Intrahepatic manometry disclosed a normal portal pressure, but
      selective mesenteric arteriography revealed occlusion of the superior mesenteric,
      splenic, and inferior mesenteric veins. Duodenal and gastric varices were noted,
      but no esophageal varices were seen. The portal vein was clearly patent. At
      surgery, a 2 cm mass was found at the superior mesenteric vein-splenic vein
      juncture, and subsequent pathologic examination confirmed the presence of suture
      material within dense fibrous tissue as the probable cause for this rare
      condition. The surgical procedure performed was a superior mesenteric vein-to
      portal vein bypass, employing ringed expanded polytetrafluoroethylene. Graft
      patency and function have been confirmed postoperatively by means of both venous
      phase mesenteric arteriography and duplex imaging. The surgical procedure was
      novel, in that it was possible to decompress the hypertensive mesenteric
      circulation from the distal superior mesenteric vein directly into the portal
      vein with a prosthetic bypass. The physiologic benefit of this operation is
      clear: the avoidance of the encephalopathic syndrome and the facilitation of
      hepatopetal blood flow.

PMID- 8523612
TI  - Morphologic change in rabbit femoral arteries induced by storage at four degrees
      Celsius and by subsequent reperfusion.
AB  - PURPOSE: Cold-stored arteries function well as microvascular autografts, but
      little is known of the morphologic changes that occur in them during cold storage
      or of further changes during reperfusion. METHODS: In part A of the study, rabbit
      femoral arteries were stored at 4 degrees C for up to 6 months. In part B rabbit
      femoral arteries were stored at 4 degrees C for up to 6 months, inserted as end
      to-end autografts into contralateral femoral arteries, and reperfused for 24
      hours. Tissue was examined by histologic study, transmission and scanning
      electron microscopy, histochemical study, immunohistochemical study, and tissue
      culture. RESULTS: Cell viability declined gradually at 4 degrees C, so that by 4
      weeks no viable cells remained. However, the extracellular framework and elastic
      lamellae remain intact. If cold-stored arteries are reinserted as autografts for
      24 hours, this accelerates breakdown of necrotic cells and reduces the thickness
      of the medial wall and internal elastic lamina but does not alter the
      extracellular framework. CONCLUSIONS: Cold storage results in acellular vascular
      grafts with intact extracellular frameworks. After 24 hours reperfusion there is
      no major change to the extracellular framework.

PMID- 8523613
TI  - Ruptured abdominal aortic aneurysm: influence of intraoperative management on
      surgical outcome.
AB  - PURPOSE: This study was designed to determine the influence of changes in
      intraoperative management on the outcome of ruptured abdominal aortic aneurysm
      (RAAA). METHODS: Retrospective review of our surgical experience of RAAA
      identified 61 patients and was separated into two periods: 1986 to 1988 (group 1
      [n = 21 patients]) and 1989 to 1994 (group 2 [n = 40 patients]). Since 1989
      operations have been conducted by two vascular surgeons without systemic
      administration of heparin and with control of suprarenal aorta if extensive
      hematoma is present, use of collagen-impregnated grafts, preferential repair with
      aortoaortic grafting, and routine use of intraoperative autotransfusion. RESULTS:
      Factors differing between the groups were use of intraoperative autotransfusion
      (4.76% in group 1 vs 80% in group 2, p < 0.00001), repair with tube grafting
      (42.8% in group 1 vs 80% in group 2, p = 0.003), number of packed homologous red
      blood cells (7.5 +/- 5.2 units in group 1 vs 3.1 +/- 3.6 units in group 2, p =
      0.008), postoperative blood loss (365 +/- 705 ml in group 1 vs 133 +/- 351 ml in
      group 2, p = 0.01). The intraoperative mortality rate was significantly lower in
      group 2 (5% vs 28.6%, p = 0.016). The only predictive factor was the use of
      intraoperative autotransfusion with a lower mortality rate in patients undergoing
      autotransfusion (p = 0.029). The postoperative mortality rate was significantly
      lower in group 2 (20% vs 52.4%, p = 0.009). Predictive factors were use of
      intraoperative autotransfusion (p = 0.0009), age of the patients (p = 0.0039),
      and repair with tube graft (p = 0.039). The odds ratio of postoperative death was
      25 times higher without intraoperative autotransfusion and seven times lower when
      a tube graft was used. CONCLUSION: Continuing efforts to achieve improvement in
      surgical technique and use of intraoperative autotransfusion were important
      determinants in lowering the postoperative mortality rate of RAAA to 20%.

PMID- 8523614
TI  - Complications of peripheral arteriography: a new system to identify patients at
      increased risk.
AB  - PURPOSE: The most quoted literature on arteriographic complications is based on
      self-reports collected during the mid 1970s. We sought to determine whether those
      results remain valid despite changes in arteriographic practice and whether
      patient subgroups at increased risk could be identified. METHODS: Five hundred
      forty-nine consecutive patients were examined after arteriography and twice over
      72 hours. Patients were telephoned at least 2 weeks later to identify delayed
      complications. The sample was divided into two groups to allow independent
      validation of suspected prognostic factors. RESULTS: The rate of major
      complications was 2.9% (16/549), but varied from 0.7% to 9.1% among three strata
      of relative risk. Rates were highest in patients studied for suspected aortic
      dissection, mesenteric ischemia, gastrointestinal bleeding, or symptomatic
      carotid artery stenosis and lowest in patients with trauma or aneurysmal disease.
      Patients studied for claudication or limb-threatening ischemia had intermediate
      risk (2.0%). Within these strata, congestive heart failure and furosemide use
      were the only variables independently associated with a significantly increased
      complication rate. CONCLUSIONS: Previous reports have overestimated the risk of
      arteriography for trauma or aneurysm but substantially underestimate the risk for
      patients with other common conditions. Such stratified complication rates are
      essential to understand relative costs and benefits of arteriography and other
      vascular imaging modalities in specific clinical situations.

PMID- 8523615
TI  - Effects of retroviral-mediated tissue plasminogen activator gene transfer and
      expression on adherence and proliferation of canine endothelial cells seeded onto
      expanded polytetrafluoroethylene.
AB  - PURPOSE: Seeding prosthetic arterial grafts with genetically modified endothelial
      cells (ECs) has the potential to substantially improve graft function. However,
      preliminary applications suggest that grafts seeded with retrovirally transduced
      ECs yield a significantly lower percent surface coverage than those seeded with
      nontransduced ECs. The objective of this study was to test the hypothesis that
      canine ECs transduced with the human tissue plasminogen activator (tPA) gene
      would have a lower rate of adherence to pretreated expanded
      polytetrafluoroethylene (ePTFE) both in vitro and in vivo and that they would
      proliferate at a slower rate on pretreated ePTFE in vitro. METHODS: Early passage
      ECs derived from canine external jugular vein were transduced with the retroviral
      MFG vector containing the gene for human tPA. ECs exposed to media alone served
      as controls. Iodine 125-labeled ECs were seeded in vitro onto ePTFE graft
      segments pretreated with canine whole blood, fibronectin (50 micrograms/ml), or
      media alone, and the percent of ECs adherent at 1 hour were determined (n = 3).
      Additional tPA-transduced and -nontransduced ECs were grown for 10 days on either
      fibronectin (50 micrograms/ml)-pretreated ePTFE wafers or tissue culture plastic
      pretreated with gelatin (1%) or fibronectin (50 micrograms/ml), and the EC
      proliferation rates were determined (n = 3). Furthermore, 125I-labeled ECs were
      seeded onto fibronectin (50 micrograms/ml)-pretreated ePTFE graft segments
      implanted as carotid and femoral artery interposition grafts (n = 3). The grafts
      were harvested after 1 hour, and the percent of ECs adherent was determined.
      RESULTS: Human tPA was detected by immunohistochemical staining in 61% +/- 5% of
      the transduced ECs and was expressed at 35.4 +/- 12.9 ng/hr/10(6) cells.
      Fibronectin and whole blood pretreatment of the ePTFE grafts led to greater EC
      adherence in vitro than did media alone (90.9% +/- 5.3% vs 77.8% +/- 5.8% vs 4.7%
      +/- 1.1%, p < or = 0.05). No significant difference in the rates of adherence or
      proliferation was seen in vitro between the transduced and nontransduced ECs. No
      significant difference in proliferation was found for the transduced ECs on the
      three matrices tested in vitro. In contrast, adherence of the transduced ECs in
      vivo was significantly lower than that of nontransduced ECs (64.7% +/- 2.1% vs
      73.7% +/- 4.1%, p < or = 0.05) 1 hour after implantation. CONCLUSIONS: Lower
      rates of surface endothelialization by genetically modified ECs in vivo do not
      appear to be due to an impaired capacity to initially adhere or proliferate on
      the synthetic graft but may result from decreased adherence after exposure to in
      vivo hemodynamic forces.

PMID- 8523616
TI  - Use of antithrombin III concentrates to correct antithrombin III deficiency
      during vascular surgery.
AB  - Congenital deficiency of antithrombin III (AT III) is the only inherited
      hypercoagulable disorder for which a concentrate of purified protein is available
      for replacement therapy during periods of increased thrombotic risk. This report
      describes how such concentrates have been used in a patient with congenital AT
      III deficiency undergoing venous surgery. A 40-year-old woman with AT III
      deficiency was evaluated for bilateral grade 3 chronic venous insufficiency.
      Noninvasive venous assessment and ascending venography revealed incompetence of
      the lower leg perforators, a patent deep venous system, and competent greater and
      lesser saphenous veins. Staged subfascial ligations were performed. Pasteurized
      AT III was administered 1 hour before surgery and at 30 hours at a dose
      calculated to increase AT-III activity to at least 120%. Perioperative AT III
      activity levels were measured. Subcutaneous heparin and oral warfarin were
      initiated the evening of surgery. An infusion of AT III increased plasma AT III
      from the baseline activity of 51% to 180%; it was 87% 13 hours later. Two
      measurements of the initial half-life of AT III were 7 and 14 hours. No
      perioperative thrombotic complications occurred. The ulcers healed, and the
      patient remains symptom free. Pasteurized AT III concentrates are now
      commercially available, easily administered, and provide a useful adjunct to the
      anticoagulation regimen of patients with AT III deficiency undergoing vascular
      surgery.

PMID- 8523617
TI  - Outcome assessment in vascular surgery--the Swedish experience. The Steering
      Committee of Swedvasc.

PMID- 8523618
TI  - Regarding "Is transcranial Doppler a worthwhile addition to screening tests for
      cerebrovascular disease?".

PMID- 8523619
TI  - A rare case of a traumatic aneurysm of the inferior thyroid artery.

PMID- 8523620
TI  - Regarding "Lipoprotein (a) levels in peripheral atherosclerotic disease".

PMID- 8523621
TI  - NASPGN commentary on A.S.P.E.N. nutrition guidelines. North American Society for
      Pediatric Gastroenterology and Nutrition. American Society for Parenteral and
      Enteral Nutrition.

PMID- 8523622
TI  - On "down-regulation of albumin synthesis in the rat by human recombinant
      interleukin-1 beta or turpentine and the response to nutrients".

PMID- 8523623
TI  - Protein energy malnutrition in severe alcoholic hepatitis: diagnosis and response
      to treatment. The VA Cooperative Study Group #275.
AB  - BACKGROUND: Active nutrition therapy and the anabolic steroid oxandrolone (OX),
      in selected patients with severe alcoholic hepatitis, significantly improved
      liver status and survival. We report here on the changes in their nutritional
      parameters. METHODS: Protein energy malnutrition (PEM) was evaluated and
      expressed as percent of low normal in 271 patients initially, at 1 month and at 3
      months. Active therapy consisted of OX plus a high caloric food supplement vs a
      matching placebo and a low calorie supplement. RESULTS: PEM was present in every
      patient; mean PEM score 60% of low normal. Most of the parameters improved
      significantly from baseline on standard care; the largest improvement seen in
      visceral proteins, the smallest in fat stores (skinfold thickness). Total PEM
      score significantly correlated with 6 month mortality (p = .0012). Using logistic
      regression analysis, creatinine height index, hand grip strength and total
      peripheral blood lymphocytes were the best risk factors for survival. When CD
      lymphocyte subsets replaced total lymphocyte counts in the equation, CD8 levels
      became a significant risk factor (p = .004). Active treatment produced
      significant risk factor (p = .004). Active treatment produced significant
      improvements in those parameters related to total body and muscle mass (ie, mid
      arm muscle area, p = .02; creatinine height index, p = .03; percent ideal body
      weight, p = .04). CONCLUSION: Deterioration in nutritional parameters is a
      significant risk factor for survival in severe patients with alcoholic hepatitis.
      This deterioration is reversible with standard hospital care. Active therapy
      further improves creatinine height index, mid arm muscle area and total
      lymphocyte counts. Hence, these later parameters appear to be the best indicators
      for follow-up assessments.

PMID- 8523624
TI  - Down-regulation of albumin synthesis in the rat by human recombinant interleukin
      1 beta or turpentine and the response to nutrients.
AB  - BACKGROUND: Inflammatory stimuli and provision of nutrients are important factors
      regulating both total liver protein synthesis and albumin synthesis. METHODS: The
      influence of interleukin-1 beta or turpentine injection and a 2-hour infusion of
      a hypocaloric mixture of glucose and amino acids on the synthesis of total liver
      protein and albumin was investigated in rats. Total liver protein synthesis was
      measured by an i.v. flooding dose of L-[2,6(3)H]phenylalanine and albumin
      synthesis was determined from the labeling of immunoprecipitated albumin and
      expressed both as a fraction of total liver protein synthesis and as an absolute
      rate. RESULTS: Interleukin-1 beta or turpentine injection stimulated total liver
      protein synthesis compared with controls, whereas albumin synthesis, both as a
      fraction of total liver protein synthesis and as an absolute synthesis rate,
      decreased. In control animals, the 2-hour i.v. infusion with glucose and amino
      acids resulted in a significant increase of total liver protein synthesis.
      Albumin synthesis as a fraction of total liver protein synthesis was not altered,
      but increased when expressed as an absolute rate in control animals. However,
      interleukin-1 beta or turpentine injection abolished this response of albumin
      synthesis to nutrient supply. CONCLUSIONS: Total liver protein synthesis
      increases under inflammatory conditions and remains responsive to nutrient
      supply. In contrast, albumin synthesis decreases under the same conditions and
      does not seem to be responsive to short-term i.v. nutrients.

PMID- 8523625
TI  - Intestinal amino acid content in critically ill patients.
AB  - BACKGROUND: The purpose of the study was to determine the concentrations of free
      amino acids and the total protein content of the human intestinal mucosa during
      critical illness. METHODS: The free amino acid and protein concentrations in
      endoscopically obtained biopsy specimens from the duodenum and the distal colonic
      segments were determined on 19 critically ill patients. The free amino acids were
      separated by ion exchange chromatography and detected by fluorescence, and the
      protein content was quantified by the method of Lowry. RESULTS: In general, the
      typical amino acid pattern of the intestinal mucosa was seen, with very high
      levels of taurine, aspartate and glutamic acid. The main difference, as compared
      to a reference series of healthy subjects, was the elevated glutamine
      concentration of the duodenal mucosa. This amino acid was unaltered in the
      descending colon and depressed in the rectum. At the same time, the glutamatic
      acid concentrations were unaltered, suggesting that the degradation of glutamine
      was not increased in the septic state of the majority of the patients studied.
      Phenylalanine and the two branched-chain amino acids, valine and leucine, were
      elevated in the duodenal mucosa, and in the colonic mucosa, methionine and
      phenylalanine were elevated; otherwise, all the other individual amino acids were
      unaltered or depressed. CONCLUSIONS: The alterations seen in mucosal free amino
      acid and protein concentrations in connection with critical illness are different
      in many respects and contrast with the findings seen after starvation or moderate
      surgical trauma.

PMID- 8523626
TI  - Is muscle protein turnover regulated by intracellular glutamine during sepsis?
AB  - BACKGROUND: Low muscle glutamine levels during sepsis are associated with reduced
      protein synthesis and elevated protein breakdown, in particular myofibrillar
      protein breakdown. It is not known if this is a causal or coincidental
      relationship. We tested the hypothesis that muscle protein turnover rates are
      directly regulated by glutamine. METHODS: Paired extensor digitorum longus
      muscles from nonseptic (sham-operated) and septic rats (16 hours after cecal
      ligation and puncture) were incubated in the absence or presence of 15 mmol
      glutamine/L. The effect of glutamine was tested in unsupplemented medium or in
      medium containing 1 mU/mL of insulin or a mixture of amino acids at normal plasma
      concentrations. Protein synthesis was measured as incorporation of 14C
      phenylalanine into protein; total and myofibrillar protein breakdown was
      determined by measuring tyrosine and 3-methylhistidine, respectively. RESULTS:
      Muscles accumulated intracellular glutamine well above normal concentrations in
      the presence of 15 mmol glutamine/L. In spite of this, protein synthesis was not
      affected by glutamine, neither when muscles were incubated in unsupplemented
      medium nor in medium containing insulin or amino acid mixture. Total protein
      breakdown was not influenced by glutamine when muscles were incubated in
      unsupplemented medium or with insulin but was reduced by glutamine in the
      presence of an amino acid mixture. Myofibrillar protein breakdown was unaffected
      by glutamine in unsupplemented medium and in medium containing insulin but was
      increased by glutamine in the presence of amino acid mixture. CONCLUSION: Reduced
      muscle protein synthesis and increased myofibrillar protein breakdown during
      sepsis are probably not caused by the low intracellular glutamine levels noticed
      in this condition.

PMID- 8523627
TI  - Essential fatty acid status in patients on long-term home parenteral nutrition.
AB  - BACKGROUND: Patients on total parenteral nutrition are known to be at risk of the
      development of essential fatty acid deficiency, presenting as a syndrome with
      scaly skin lesions and characterized by low plasma and erythrocyte linoleic acid
      concentrations. The essential fatty acid status of patients on long-term home
      parenteral nutrition who do have access to oral feeds has not been studied.
      METHODS: With the use of an isocratic high-performance liquid chromatography
      method, fatty acids were measured in the erythrocytes and plasma of 25 nonfasting
      patients on long-term home parenteral nutrition and the findings compared with
      those of 46 hospital outpatients not on nutrition support and five laboratory
      staff. RESULTS: Statistically significant differences in the two groups were
      limited to the erythrocytes. Linoleic acid was significantly lower (25.2 vs 40.7
      mumol/10(6) red blood cells, p < .0001) and showed a significant correlation with
      triceps skinfold thickness (r = .52, p = .013). Palmitoleic and oleic acids were
      higher in patients than controls (10.8 vs 8.4 mumol/10(6) red blood cells, p =
      .009; 61.2 vs 51.7 mumol/10(6) red blood cells, p = .003). CONCLUSIONS: Despite
      IV linoleic acid administration, patients on long-term home parenteral nutrition
      have low erythrocyte stores of this essential fatty acid. This appears to be
      related to their low body fat stores. We suggest that they may be using much of
      the infused linoleic acid as an energy source and therefore are at risk of
      subclinical essential fatty acid deficiency.

PMID- 8523628
TI  - Spinal osteomyelitis after TPN catheter-induced septicemia.
AB  - Osteomyelitis of the spine is a well-recognized delayed manifestation of
      septicemia but has not been recognized as a complication of total parenteral
      nutrition. We report five cases of spinal osteomyelitis that were clinically
      recognized 1 to 13 months after total parenteral nutrition catheter-induced
      septicemia. Radiographic evidence of osteomyelitis was seen in all five patients.
      In three patients, culture of bony aspirates was positive for the same organism
      as from the blood. In one case, the diagnosis was established by histology, and
      in one the diagnosis was based on radiographic and radionuclide evidence of
      osteomyelitis. The organism responsible was Staphylococcus aureus in two cases,
      Candida albicans in another two cases and C tropicalis in one case. The septic
      episode that preceded osteomyelitis was treated with systemic antibiotics and
      catheter removal in four patients, and antibiotics without catheter removal in
      one patient. Nevertheless, osteomyelitis occurred, requiring bracing or operative
      debridement as well as prolonged antibiotic therapy. Spinal osteomyelitis may
      occur as a delayed manifestation of total parenteral nutrition catheter-induced
      septicemia. Prompt and effective treatment of septicemia is indicated but may not
      always be sufficient. Clinical suspicion is the key to the correct and early
      diagnosis of osteomyelitis and therefore to adequate treatment.

PMID- 8523629
TI  - Growth hormone, glutamine, and a modified diet enhance nutrient absorption in
      patients with severe short bowel syndrome.
AB  - BACKGROUND: Massive loss of intestinal surface area results in the short bowel
      syndrome characterized by malabsorption of fluid, electrolytes, and other
      nutrients. Although the remaining bowel undergoes morphological and functional
      adaptation, often these changes are inadequate to support the individual by
      enteral feedings, and parenteral nutrition is required to prevent dehydration,
      electrolyte disturbances, and malnutrition. Substances such as growth hormone,
      glutamine, and fiber exert bowel-specific trophic effects and either directly or
      indirectly influence nutrient absorption. This study was undertaken to determine
      whether the co-administration of exogenous growth hormone, supplemental
      glutamine, and a modified fiber-containing diet could enhance nutrient absorption
      in patients who had undergone massive intestinal resection. METHODS: Ten patients
      (5 men, 5 women, aged 43 +/- 4 years) with short bowel syndrome were studied 6 +/
      1 years after surgical resection. All patients were admitted to the Clinical
      Research Center for a 28-day period; the first week served as a control period
      when nutritional (enteral and parenteral) and medical management simulated usual
      home therapy. Thereafter, eight patients received exogenous growth hormone,
      supplemental glutamine, and a modified high-carbohydrate, high-fiber diet. Two
      patients were treated with the modified diet alone. The efficiency of net
      nutrient absorption (percent absorbed) for total calories, protein, fat,
      carbohydrate, water, and sodium was calculated from the measured nutrient intake
      and stool losses. RESULTS: Three weeks of treatment with growth hormone,
      glutamine, and a modified diet increased total caloric absorption from 60.1 +/-
      6.0% to 74.3 +/- 5.0% (p < or = .003), protein absorption from 48.8 +/- 4.8% to
      63.0 +/- 5.4% (p < or = .006), and carbohydrate absorption from 60.0 +/- 9.8% to
      81.5 +/- 5.3% (p < or = .02). Fat absorption did not change (61.0 +/- 5.3% to
      60.3 +/- 7.9%, p = NS). Water and sodium absorption increased from 45.7 +/- 6.7%
      to 65.0 +/- 7.3% (p < or = .002) and from 49.0 +/- 9.8% to 69.6 +/- 6.5% (p < or
      = .04), respectively. These absorptive changes resulted in a decrease in stool
      output (1,783 +/- 414 g/d control period vs 1,308 +/- 404 g/d third week of
      treatment, p < or = .05). Treatment with diet alone did not influence nutrient
      absorption or stool output. CONCLUSIONS: The combined administration of growth
      hormone, glutamine, and a modified diet enhanced nutrient absorption from the
      remnant bowel after massive intestinal resection. These changes occurred in a
      group of patients that had previously failed to adapt to the provision of enteral
      nutrients. This therapy may offer an alternative to long-term dependence on total
      parenteral nutrition for patients with severe short bowel syndrome.

PMID- 8523630
TI  - The depression of hepatic drug conjugation reactions in rats after lipid-free
      total parenteral nutrition administered via the portal vein.
AB  - BACKGROUND: Total parenteral nutrition provides nutrition support in patients who
      are unable to eat. Long-term parenteral nutrition is accompanied by alterations
      in gut and liver function including changes in drug metabolism. This study
      examined the effects of lipid-free total parenteral nutrition in rats on (1) the
      overall elimination pharmacokinetics of acetaminophen, (2) changes in sulfation
      and glucuronidation pathways during acetaminophen elimination, and (3) hepatic
      drug metabolizing enzyme activities determined in vitro. METHODS: Chronic
      indwelling catheters were implanted in the aorta, inferior vena cava, and portal
      vein of adult male Sprague-Dawley rats. Total parenteral nutrition, consisting of
      25% dextrose, 5% amino acids, electrolytes, and vitamins, was infused via the
      portal vein for up to 14 days. Acetaminophen pharmacokinetics were characterized
      in vivo and selected drug metabolizing enzyme activities were determined in
      vitro. RESULTS: Parenteral nutrition for 10 days decreased the total clearance of
      acetaminophen by 23% (from 11.5 +/- 1.4 to 8.9 +/- 1.4 mL/min per kg; p < .05)
      and decreased the formation clearance to acetaminophen sulfate (from 6.2 +/- 0.4
      to 3.9 +/- 0.5 mL/min per kg; p < .05). Parenteral nutrition decreased microsomal
      cytochrome P450 concentration (47%), p-nitroanisole demethylase activity (68%)
      and p-nitrophenol UDP-glucuronosyltransferase activity (58%). Cytosolic
      glutathione-S-transferase activity towards 1-chloro-2,4-dinitrobenzene decreased
      29%. Sulfotransferase activity towards p-nitrophenol and acetaminophen was
      decreased 48% and 25%, respectively. CONCLUSION: Lipid-free, total parenteral
      nutrition depresses drug conjugative metabolism in rats. The magnitude of this
      effect in humans remains to be investigated.

PMID- 8523631
TI  - Manganese deposition in the brain during long-term total parenteral nutrition.
AB  - BACKGROUND: Manganese deposition was suspected in a pediatric patient who
      received long-term total parenteral nutrition. T1-weighted magnetic resonance
      images revealed high intensity areas in the globus pallidus. This study was
      designed to clarify if these abnormal findings were related to manganese
      deposition and clinical neurological manifestations. METHODS: Whole-blood
      manganese concentrations were measured during manganese supplementation to total
      parenteral nutrition and after 5 months without manganese. Magnetic resonance
      images were also examined on each occasion and compared with the blood level of
      manganese. RESULTS: The whole-blood manganese level during supplementation was
      135 micrograms/L (normal range 14.6 +/- 4.7 micrograms/L), whereas the level was
      20 micrograms/L after a manganese-free period of 5 months. Accompanied with
      normalization of manganese level, abnormal high intensity lesions in the globus
      pallidus on T1-weighted images also disappeared. No neurological manifestation
      related to the high manganese level was recognized. CONCLUSIONS: It is probable
      that the high manganese level was elicited by manganese supplementation to total
      parenteral nutrition. This high manganese condition was confirmed by the
      measurement of whole-blood manganese level, which was associated with the
      abnormal high intensity lesions on T1-weighted magnetic resonance images.

PMID- 8523632
TI  - The accumulation and energy load of exogenous lipids in cirrhotic rat liver after
      partial hepatectomy.
AB  - BACKGROUND: The suitability of three energy substrates, glucose, medium-chain
      triglycerides (MCT) and long-chain triglycerides (LCT), was studied in cirrhotic
      rats after a partial hepatectomy. METHODS: Rats with thioacetamide-induced
      cirrhosis underwent a 70% hepatectomy, and were divided into three groups. Each
      group was then injected with 14C-labeled glucose, 14C-labeled MCT or 14C-labeled
      LCT, respectively. The subsequent tissue distribution of 14C and the cumulative
      amount of expired 14CO2 were determined. In a second experiment, the 70%
      hepatectomized cirrhotic rats received total parenteral nutrition (TPN). The
      source of the nonprotein calories was 100% glucose (glucose group), 60% MCT + 40%
      glucose (MCT group), and 60% LCT + 40% glucose (LCT group). The adenylate energy
      charge and the glycogen content in the liver remnant were determined. RESULTS:
      The tissue distribution of 14C revealed that the fat emulsions accumulated
      preferentially in the liver. One hour after the partial hepatectomy, the
      concentration of 14C-labeled MCT in the liver remnants was threefold higher than
      in sham-operated controls. Similarly, the concentration of 14C-labeled LCT was
      twofold higher. The adenylate energy charge in the glucose group with TPN
      recovered to preoperative levels within 1-hour after the partial hepatectomy,
      whereas the LCT group with TPN showed a 24-hour delay in their recovery. The MCT
      group with TPN exhibited an intermediate time course. CONCLUSIONS: It is
      suggested that the specific accumulation of MCT and especially LCT emulsions in
      the cirrhotic liver remnant acts as an energy load rather than an energy
      substrate.

PMID- 8523634
TI  - Transverse Witzel-T-tube feeding jejunostomy.
AB  - BACKGROUND: In patients prone to recurrent aspiration, a feeding jejunostomy is
      only performed to ensure adequate nutrition. A popular method for placement of
      the jejunostomy tube is the Witzel procedure, employing a sersosal tunnel on the
      antimesenteric border. The Witzel procedure, however, frequently suffers from the
      complication of tube dislodgement and obstruction due to narrowing of the
      intestinal lumen. METHODS: To minimize the complications associated with the
      standard Witzel method, we modified the procedure wherein a T-tube is substituted
      for a standard French rubber catheter, and transversely sutured to the mesenteric
      border. We believe that the placement of the Witzel line in the transverse plane
      minimizes the risk of obstruction, and substitution of a T-tube for a standard
      French catheter should reduce the incidence of tube dislodgement. RESULTS: The
      Transverse Witzel T-tube feeding jejunostomy has been performed successfully in
      30 patients without any complications of tube dislodgement or leaks, and no tube
      to date has been difficult to remove. Length of tube use has ranged from 1 to 6
      months, and no postoperative complications have been observed in this group.
      CONCLUSIONS: The Transverse Witzel T-tube jejunostomy is an effective and rapid
      technique for placement of a feeding tube. No serious complications have been
      observed, and the complication of tube dislodgement appears to be decreased
      compared to the standard Witzel procedure.

PMID- 8523635
TI  - Long-term morbidity following jejunoileal bypass: the continuing potential need
      for surgical reversal.

PMID- 8523633
TI  - Effect of different combinations of dietary additives on bacterial translocation
      and survival in gut-derived sepsis.
AB  - BACKGROUND: Dietary arginine, glutamine, and fish oil each have been shown to
      improve resistance to infection. The purpose of this study was to assess the
      potential benefit of different combinations and amounts of these components on
      bacterial translocation and related mortality during gut-derived sepsis. METHODS:
      Balb/c mice were fed for 10 days with an AIN-76A diet supplemented with different
      combinations and percentages of arginine, glutamine, glycine, fish oil, and
      medium-chain triglycerides. Controls were fed a complete AIN-76A diet or chow.
      After 10 days of feeding, all animals were transfused. On day 15, the animals
      were gavaged with 10(10) 111In-radiolabeled or unlabeled Escherichia coli and
      given a 30% burn injury. Animals gavaged with unlabeled bacteria were observed
      for survival (n = 317). Groups that showed the best survival as well as control
      groups were gavaged with labeled bacteria and killed 4 hours postburn (n = 60)
      for harvest of mesenteric lymph nodes, liver and spleen. RESULTS: Mice fed diets
      enriched with 5% fish oil + 2% arginine, 2% arginine + 2% glutamine, or 5% fish
      oil + 2% glutamine had higher survival than control groups. The animals fed fish
      oil+glutamine had significantly reduced translocation to the liver and spleen.
      Animals fed arginine+glutamine had an enhanced ability to kill translocated
      organisms in the liver compared with other groups. Fish oil+arginine improved
      both barrier function and microbial killing. CONCLUSIONS: Feeding with
      arginine+glutamine, fish oil+arginine, or fish oil+glutamine supplemented diets
      positively affects the outcome in a gut-derived sepsis model.

PMID- 8523636
TI  - Intensive care in the developing world: is it worth the cost?

PMID- 8523637
TI  - A rapid community based health evaluation of pregnant women in low socioeconomic
      settlements of Karachi.
AB  - A rapid nutritional and health evaluation of a random sample of 163 pregnant
      women was conducted in low socioeconomic settlements of Karachi, with the
      objective of determining the morbidity and nutritional status of pregnant women.
      These data are expected to be used in an ongoing community-based antenatal care
      programme. Twenty-nine percent of women reported fever, 14 percent diarrhoea and
      33 percent respiratory infections in the previous week. Mean weight was 54.8 (+/-
      10.6) kg, mean height was 151.6 (+/- 6.0) cm and mean midarm circumference was
      25.6 (+/- 3.2) cm. The mean uterine height at gestational ages 8 months and over
      was 32.1 (+/- 10.2) cm which is below the 10th percentile. These results suggest
      a chronic, mildly malnourished population with a high rate of infections.
      Specifically, we suggest that maternal height and uterine height be used to
      assess women at high risk for low birthweight.

PMID- 8523638
TI  - The pattern of bone marrow infiltration in non-Hodgkin's lymphomas.
AB  - The pattern of bone marrow infiltration in 40 consecutive cases of non-Hodgkin's
      lymphomas (NHLs) having marrow involvement is presented. For histological break
      up, working formulation of NHLs was used. Low grade NHLs (50%) were the
      commonest, followed by intermediate (32.5%) and high grade NHLs (17.5%),
      respectively. Histologically, small lymphocytic type (32.5%) was the commonest,
      followed by diffuse small cleaved cell (15%) type; follicle small cleaved cell,
      diffuse mixed small and large cell as well as lymphoblastic types were equally
      frequent (12.5% each). Other histological types were less common. The pattern of
      infiltration of the bone marrow was diffuse in 76.7% of intermediate, 70% of low
      and 100% of high grade NHLs. It was focal random (non-paratrabecular) in 15% of
      low grade and 15.4% of intermediate grade NHLs. Focal paratrabecular pattern was
      evident in 15% of low grade and 7.7% of intermediate grade NHLs.

PMID- 8523639
TI  - Are non-diabetic women with abnormal glucose screening test at increased risk of
      pre-eclampsia, macrosomia and caesarian birth?
AB  - To determine, in non-diabetic women, the relationship of abnormal glucose
      screening test, with the incidence of pre-eclampsia, macrosomia and caesarian
      delivery, from 1988-92, 5646 consecutive women attending antenatal clinic were
      screened with a glucose challenge test (GCT) on their first visit (usually at 16
      20 weeks); those with risk factors i.e., history of unexplained perinatal loss,
      macrosomia or family member with diabetes and an initial abnormal screening test
      were rescreened at 28-32 weeks. In 482 cases the GCT was abnormal (plasma glucose
      value was > 140 mg% 2 hours after 75 g glucose challenge). Of these, 292 had one
      or more abnormal critical values at a 75 g-3 hour oral glucose tolerance test
      (GTT) and they were treated to maintain euglycaemia. The rest (n = 190) had no
      evidence of glucose intolerance with no abnormal values at the GTT. The subjects
      were divided into 3 groups based on GCT values; A, randomly selected subjects
      with a normal GCT (n = 1000); B, those with abnormal GCT but normal GTT (n =
      190); and C, those with abnormal GTT (n = 292). The variables studied were age,
      gravidity, parity, gestational age at delivery, pre-eclampsia, birth-weight and
      mode of delivery. The incidence of pre-eclampsia and caesarian birth varied,
      being the lowest in Group A (3.9% and 11.9% respectively) and then rising through
      group B (6.3% and 16.3% respectively) to the highest in Group C (12.6% and 26.0%
      respectively; test of linear trend, p < 0.05). For macrosomia, the incidence
      increased from Group A to B but there was a drop in Group C.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8523640
TI  - Granulocytic sarcoma in patients with chronic myeloid leukaemia.
AB  - Granulocytic sarcoma is an unusual variant of myeloid malignancy most commonly
      encountered in the course of chronic or acute myeloid leukaemia. Of 60 patients
      of chronic myeloid leukaemia studied over 21 months, we encountered 6 (10%) cases
      of granulocytic sarcoma. Four of these had granulocytic sarcoma on their first
      presentation. All those who were receiving hydroxyurea did not fare well but one
      who was put on DAT (daunorubicin, cyftosine arabinocide, 6 thioguanine)regimen
      went into remission with complete disappearance of lesions.

PMID- 8523641
TI  - Peripheral blood progenitor cell transplant: a way forward.

PMID- 8523642
TI  - Pulsed dye laser lithotripsy for ureteric calculi.

PMID- 8523643
TI  - A study of serum vitamin B12 and folate levels in patients of megaloblastic
      anaemia in northern Pakistan.

PMID- 8523644
TI  - A serological antibody survey for Toxoplasma gondii in twin cities of Rawalpindi
      and Islamabad.

PMID- 8523645
TI  - Isolated posterior fossa hypertension and brainstem compression caused by
      entrapped Dandy-Walker cyst: a case report.
AB  - Lateral ventricular shunting alone is often considered to be adequate treatment
      for hydrocephalus caused by Dandy-Walker syndrome. A patient is presented in whom
      progressive spastic tetraparesis and signs of severe brainstem compression
      developed due to an entrapped posterior fossa cysts, in spite of an adequately
      functioning lateral ventricular shunt. Addition of a cystoperitoneal shunt
      resulted in rapid resolution of symptoms and deficits. This case illustrates that
      potentially fatal brainstem compression and dangerous posterior fossa
      hypertension may develop if the posterior fossa cyst does not communicate with
      the lateral ventricles, where the shunt is placed.

PMID- 8523646
TI  - Salmonella paratyphi A induced pancytopenia--a new association.
AB  - A case of salmonella paratyphi A fever with reversible pancytopenia in a 15 years
      old boy who presented with history of high grade continuous fever, epistaxis and
      haemoptysis, relative bradycardia and splenomegaly is described here. A brief
      review of the literature on possible causes of reversible pancytopenia in this
      case is also discussed.

PMID- 8523647
TI  - Case of pelvic relapse in a child suffering from acute lymphoblastic leukemia.
AB  - We describe here a case of an eight years old child suffering from acute
      lymphoblastic leukemia. She developed pelvic infiltration of leukemic cells while
      in bone marrow remission and receiving maintenance chemotherapy. She also
      developed leukemic infiltration of Central Nervous System and died of
      complications resulting from massive pelvic relapse. With greater number of
      children in bone marrow and CNS remission, the issue of possible greater
      predisposition to extramedullary relapse has been discussed. The need for greater
      vigilance towards pelvic surveillance has been stressed.

PMID- 8523648
TI  - Transverse ectopia of the testis: a case report.
AB  - A case of transverse ectopia of the testis in a man of 30 years is presented. The
      patient was admitted for a right inguinal herniorrhaphy and the finding of
      ectopic testis was accidental.

PMID- 8523649
TI  - Hepatitis B vaccination.

PMID- 8523650
TI  - [Calcitonin gene-related peptide and human atrial natriuretic hormone levels in
      response to cardiac operation under high dose fentanyl anesthesia].
AB  - To elucidate a role of calcitonin gene-related peptide (CGRP) in anesthesia and
      surgery with cardiopulmonary bypass (CPB), we measured CGRP which is reported to
      be a marker for fluid overload, simultaneously with HANP (human atrial
      natriuretic hormone) in 12 patients during high dose fentanyl anesthesia (50-70
      microgram. kg-1). Plasma concentration of CGRP increased to 3 times of the value
      during preanesthetic phase at 30 min after initiation of CPB. A 3-fold increase
      compared with control in CGRP occurred 30 min after initiation of CPB. A 3-fold
      increase in HANP also occurred just before termination of CPB. But, there was no
      correlation between plasma levels of CGRP and HANP. The changes in CGRP did not
      relate with those of pulmonary capillary wedge pressure. The results of the
      present study suggest that the mechanism for the increase is unclear, and CGRP
      could be influenced during cardiac or coronary artery surgery using CPB.

PMID- 8523651
TI  - [Risk factors for pulmonary hypertensive crisis (PHC) following VSD repair in
      infants].
AB  - We examined 100 patients who had undergone VSD repair from 1988 to 1991 to
      determine the risk factors to induce PHC postoperatively. We analyzed age,
      weight, preoperative Pp/Ps, Rp/Rs, Qp/Qs, and postoperative Pp/Ps using
      discriminant analysis. We had 34 cases of pulmonary hypertension (PH: Pp/Ps >
      0.7) preoperatively. Among 100 cases, PHC developed in 6 patients and 2 of them
      died postoperatively. Incidence of PHC in all patients was 6%, and that in
      patients with PH was 18%. PHC fatality rate was 33%. The analysis revealed that
      the occurrence of PHC was significantly higher among those whose ages were below
      2.1 years, and with weight of under 9.85 kg, preoperative Pp/Ps > 0.73, Rp/Rs <
      0.34, and postoperative Pp/Ps > 0.43. In those with preoperative PH, the risk for
      PHC increased significantly when their postoperative Pp/Ps exceeded 0.44.

PMID- 8523652
TI  - [Effects of anesthetic drugs and temperature on brain stem and mid-latency evoked
      potentials].
AB  - We evaluated the effects of anesthetic drugs and temperature on brain stem and
      mid-latency evoked potentials (BAEP and MLAEP) in 20-patients who were scheduled
      for elective cardiac operation using cardiopulmonary bypass with moderate
      hypothermia. At esophageal temperature of 36 degrees C, the latency of MLAEP was
      slightly prolonged by the increase of fentanyl dose, which suggested that the
      latency prolongation of MLAEP could not block the oscillation of auditory
      stimulation. At esophageal temperature of 27 degrees C, the latency of MLAEP
      nearly disappeared, and the latency of MLAEP gradually returned with the recovery
      of the esophageal temperature. The latency of BAEP was markedly prolonged at 27
      degrees C and returned to the normal latency at 36 degrees C. The latency of
      MLAEP retained by high dose fentanyl suggests that patients may be aware during
      cardiopulmonary bypass at normothermia, and BAEP may be one of the useful brain
      function monitors during cardiopulmonary bypass.

PMID- 8523653
TI  - [Effects of exogenous adenosine on myocardial recovery after acute hemorrhage].
AB  - This study was designed to investigate whether reperfusion with adenosine had an
      effect on myocardial high energy phosphate levels and cardiac function in hearts
      extracted from acutely hemorrhaged rats. Rats were bled to a mean arterial
      pressure of 0 mmHg for 5, 10 or 15 minutes and hearts were removed and assigned
      to one of three groups: 1) Hearts freeze clamped for measuring high energy
      phosphates; 2) Hearts perfused by Langendorff method at a constant perfusion
      pressure of 90 mmHg for 30 minutes followed by freeze clamping and determining
      high energy phosphates and; 3) Hearts perfused with adenosine (20 microM) and
      treated in the same way as in group 2. In group 1 myocardial ATP was
      significantly reduced as compared with control. When reperfusion started within
      10 min, ATP contents recovered to the levels of control, and there were no
      significant changes between groups 2 and 3. LVP and LV dp/dt in group 3 were
      significantly higher than those in group 2. When reperfusion started after 15
      min, ATP remained at a low level and few hearts could be resuscitated. These
      findings suggest that early resuscitation with adenosine might facilitate cardiac
      recovery following acute hemorrhage.

PMID- 8523654
TI  - [Effect of prostaglandin E1 on arterial ketone body ratio during and after
      hepatectomy].
AB  - We evaluated the effect of prostaglandin E1 (PGE1) on arterial ketone body ratio
      (AKBR) in patients undergoing hepatectomy. Sixteen patients were divided into two
      groups. In the PGE1 group (n = 8), 0.02-0.05 micrograms.kg-1.min-1 of PGE1 was
      administrated intravenously throughout the operation. In the control group (n =
      8) patients were not given PGE1. AKBR decreased significantly during the
      operation; the decrease was in the same degree in both groups. Although AKBR rose
      in both groups after the operation, it returned more rapidly to the normal level
      in the PGE1 group compared with the control group. On the third postoperative
      day, the value of AKBR in the PGE1 group was significantly higher than that of
      the control group. These findings suggest that the intraoperative administration
      of PGE1 is valuable for protection against postoperative hepatic dysfunction
      induced by hepatectomy.

PMID- 8523655
TI  - [The mu, delta and kappa properties of various opioids].
AB  - Recently, the highly selective mu, delta and kappa radiolabeled opioid ligands,
      such as 3H-DAGO (mu ligand), 3H-DPDPE (delta ligand) and 3H-U69593 (kappa ligand)
      are available. Using the kappa-homogeneous preparations from human placenta and
      mu-enriched gerbil cerebellum membrane preparations with these highly selective
      radiolabeled opioid ligands, clinically used opioids were tested for their mu,
      delta and kappa properties. The mu agonists such as morphine and fentanyl display
      a very low affinity for delta and kappa receptor. Among the agonist-antagonist,
      buprenorphine and butorphanol appeared to be the most highly selective agonists
      for mu and kappa opioid receptors, respectively. Most ligands identified as
      specific agonists are in fact only selective and appear to interact at more than
      one receptor type.

PMID- 8523656
TI  - [Analgesic efficacy of E2078 (dynorphin analog) in patients following abdominal
      surgery].
AB  - Studies were carried out to elucidate the efficacy and safety of E2078, a
      metabolically stable dynorphin analog, in patients with severe pain following
      lower abdominal surgery. E2078 was administered intramuscularly in a single dose
      of 1 to 15 mg. The efficacy was determined by evaluating the pain intensity score
      (PI) and global improvement rating (GIR) by the investigator. E2078 exhibited
      analgesic effect at doses of 10 mg or more. At the dose of 10 mg (n = 24). PI
      decreased from 3.0 to 1.3, and GIR was 83%. When the dose was increased to 12.5
      mg (n = 15), PI improved from 3.0 to 1.3, and GIR was 100%. The improvement in
      PI, GIR and the duration of efficacy were 3.0 to 0.8, 100% and 6 hours 40 minutes
      with E2078 15 mg (n = 10), respectively. E2078 did not produce any adverse
      effects at doses of up to 15 mg. The results of the present study indicate that
      E2078 begins to exhibit analgesic effect at a dose of 10 mg, and at 15 mg its
      effect is comparable to that of pentazocine 15 mg.

PMID- 8523657
TI  - [Effects of preoperatively administered flurbiprofen axetil on the action of
      inhaled anesthesia and postoperative pain].
AB  - Flurbiprofen axetil (FP) was evaluated in a randomized study relative to placebo
      in 26 patients undergoing endonasal ethmoidectomy. The FP group (n = 13) was
      administrated 1 mg.kg-1 FP 15 minutes before operation during a half hour.
      Likewise, the control group (n = 13) received intravenous NaCl 0.9%.
      Concentration and the quantity consumed of sevoflurane, perioperative body
      temperature, postoperative pain and on-demand dicrofenac sodium consumption were
      measured. No significant differences were observed concerning concentration and
      the quantity consumed of sevoflurane. Body temperature of the FP group fell
      significantly before infusion. The FP group showed lower pain scores and required
      less dicrofenac sodium than the control group (P < 0.05). This study suggests
      that preoperative FP infusion relieves postoperative pain, but does not affect
      the action of the inhalation anesthetic.

PMID- 8523658
TI  - [Comparison of airway complications on tracheal extubation in deeply sevoflurane
      anesthetized versus awake children].
AB  - We investigated the incidence of respiratory complications and oxygen saturation
      level during emergence from sevoflurane anesthesia in children whose tracheas
      were extubated while they were anesthetized or after they became awake. Thirty
      children, aged 1-10 years, were studied. Anesthesia was induced with sevoflurane
      or thiopental and maintained with nitrous oxide, oxygen and sevoflurane. After
      nitrous oxide was discontinued at the end of surgery, the patients were randomly
      assigned to two groups: deeply anesthetized extubation group (anesthetized group)
      and awake extubation group (awake group). In anesthetized group, the patients
      were extubated while they were administered 1.5% or higher sevoflurane in 100%
      oxygen. In awake group, extubation was performed while the patients were awake.
      The incidence of respiratory complications such as apnea, laryngospasm,
      bronchospasm and arrythmias was not significantly different between the two
      groups. There was a significantly higher incidence of the airway obstruction but
      less incidence of cough and breath-holding in anesthetized group. Oxygen
      saturation level before and after tracheal extubation was not different between
      the two groups. In conclusion, with proper attention to airway obstruction, it
      may be possible to extubate while children are deeply anesthetized with
      sevoflurane.

PMID- 8523659
TI  - [A case of emergency admission for CO2 narcosis in a patient with amyotrophic
      lateral sclerosis].
AB  - A 68-year-old man with severe dyspnea was admitted as an emergency case. He had
      no past history of any respiratory or neuromuscular diseases. Immediately after
      insufflation of oxygen, respiratory arrest occurred. The blood gas analysis
      showed hypoxemia and severe hypercapnia (PaO2; 32 mmHg, PaCO2; 127 mmHg). We
      diagnosed as CO2 narcosis, and he was treated with a respirator in the ICU. He
      showed nonflaccid bilateral diaphragmatic paralysis and muscle atrophy of the
      upper extremities. As the EMG showed giant spikes of neurogenic pattern, he was
      diagnosed as ALS. Weaning from the respirator failed because of his respiratory
      muscle fatigue. He was given rehabilitation during the day time and ventilatory
      support with the respirator during the night. We conclude that if we meet with an
      emergency patient with CO2 narcosis without any pulmonary disorder, we have to
      suspect neuromuscular diseases, e.q. ALS. In some of such cases, mechanical
      ventilation supports social rehabilitation.

PMID- 8523660
TI  - [A case of metastatic lung cancer detected by intraoperative fiberoptic
      bronchoscopy].
AB  - A 64-year-old woman, who had undergone left-pneumonectomy one and a half month
      before, had the resection of metastatic brain tumor. After the end of the
      surgical procedure, we performed the fiberoptic bronchoscopy for suctioning
      secretion because we had decided to extubate the endotracheal tube in the
      operating room. By chance we found a metastatic lung tumor at the entrance of the
      right upper bronchus. This could not be identified even by means of the
      postoperative chest X-ray and CT scan. We anesthesiologists should be thoroughly
      trained in the technique of fiberoptic endoscopy. With this technique we can
      contribute to the better perioperative management of the patient. It is also
      important that enough number of fiberscopes are available.

PMID- 8523661
TI  - [The limitation of synchronization of pressure support ventilation (PSV) in
      ARDS].
AB  - PSV has been increasingly used as a partial ventilatory support for various types
      of respiratory failure. We experienced premature breath termination and double
      triggering in a patient with ARDS during PSV, and investigated the cause of this
      phenomenon using respiratory muscle pressure (Pmus). The analysis confirmed that
      the respiratory muscles and the ventilator did not coordinate synchronously in
      the patient with very low compliance of the respiratory system. The limitation of
      synchronization was attributable to fixed flow termination criteria in the
      present PSV algorithm. When dissynchronization is not manageable, other
      ventilatory modes (eg, APRV, PCV) allowing spontaneous ventilation should be
      considered as an alternative.

PMID- 8523662
TI  - [The anesthetic management of a patient with Fabry's disease].
AB  - There are no reports of anesthesia for a patient with Fabry's Disease in Japan.
      Fabry's Disease is a rare hereditary disease that is characterized by alpha
      galactosidase deficiency caused by deposition of glycolipid in many organs. The
      disease may be complicated by cardiac ischemic disease, neurological disorder and
      renal failure. The patient is a 45-year-old female with cholelithiasis who
      underwent cholecystectomy. This patient had been hospitalized repeatedly for the
      past 15 years because of the chronic pyelits, and hyperglycemia, and nephrosis.
      She developed chronic renal failure, hemodialysis was started when diagnosis of
      Fabry's Disease was made at age of 41. Preoperative electrocardiogram revealed
      ischemic change on leads II, V5 and V6. Nifedipine was administered for
      hypertension. The anesthesia was induced with thiopental followed by vecuronium
      for endotracheal intubation, and maintained with nitrous oxide, oxygen and
      isoflurane. Accompanied by nicardipine for hypertension, and vecuronium for
      muscle relaxation using a neurotransmission monitor (Relaxograph), nitroglycerin
      was continuously infused. We avoided the effect of atropine for reversal of
      muscle relaxation because most of the patients were complicated with
      hypohidrosis. During administration of nitroglycerin and nicardipine, the
      neuromuscular blocking effects of vecuronium could be prolonged. The
      neuromuscular monitoring was useful in this case.

PMID- 8523663
TI  - [A case of graft-versus-host disease following red cell concentrate (MAP-CRC)
      transfusion].
AB  - We report a case of transfusion-associated graft-versus-host disease (GVHD). A 79
      year-old woman with Hodgkin's disease, respiratory failure and severe anemia who
      had been treated with two courses of chemotherapy was transfused with red cell
      concentrate (MAP-CRC) and fresh frozen plasma (FFP) in the ICU. On the 7-9th days
      after transfusion, she developed a diffuse erythematous rash mainly on the chest,
      high fever, liver dysfunction and thrombocytopenia. Despite treatment with
      immunoglobulin products and methylprednisolone, her condition deteriorated
      rapidly, and she died of multiple organ failure on the 7th day after appearance
      of rash. Skin biopsy demonstrated typical features of acute GVHD, suggesting that
      MAP-CRC-associated GVHD had occurred.

PMID- 8523664
TI  - [Usefulness of measurement of mast cell tryptase for differential diagnosis of
      anaphylaxis and anaphylactoid reaction].
AB  - We described a case of anaphylaxis diagnosed by the evaluation of plasma mast
      cell tryptase and a case of anaphylactoid reaction. In a patient undergoing
      pulmonary lobectomy, anaphylaxis, showing the elevation of plasma tryptase, was
      provoked by physiological glue for hemostasis during the operation. During the
      operation, cardiovascular collapse occurred suddenly, at which time the cause was
      not diagnosed. After completion of the operation and removal of drapes, diffuse
      urticaria with wide erythema on the torso and the upper extremity was noticed.
      Suspecting allergic adverse reaction, plasma tryptase was measured 2h and 5h
      after the start of the episode, showing 34.6 ng.ml-1 at 2h and 15.3 at 5h.
      Because these elevations of plasma tryptase indicated degranulation of mast
      cells, evaluation of the causative drugs was performed 7 weeks after the episode.
      Physiological glue was confirmed to be causative drug. In another patient for
      total hysterectomy and bilateral oophorectomy, adverse reaction occurred after
      completion of the operation and extubation. Increase in plasma histamine
      concentration to 4.94 ng.ml-1 that could induce systemic reaction was noticed;
      however, concentrations of plasma tryptase 25 min, 3h and 7h after the episode
      were not elevated. This finding indicated that the adverse reaction was not based
      on degranulation of mast cell, and was anaphylactoid reaction provoked by
      nonspecific histamine-release. In conclusion, measurement of plasma tryptase is a
      useful method for differential diagnosis of anaphylaxis and anaphylactoid
      reaction.

PMID- 8523665
TI  - [The importance of SpO2 and FIO2 for anesthetic management for Norwood's
      operation].
AB  - The systemic and pulmonary vascular resistance needs to be balanced before
      cardiopulmonary bypass (CPB) and high flow pulmonary circulation must be avoided
      after CPB during anesthetic management for Norwood's operation. The level of SpO2
      was controlled at 75-80% to maintain systemic and pulmonary circulation. The
      relationship between the change of color of the lung and level of SpO2 through
      gradual increase of pulmonary blood flow was carefully observed. As SpO2 level
      increased, lung changed color from white, pink to red. The SpO2 level of lung in
      red color was above 85%, suggesting high flow pulmonary circulation. To decrease
      the level of SpO2, FIO2 was decreased. The lung changed to pink and balance of
      systemic and pulmonary circulation was maintained, reconfirming that control of
      SpO2 and FIO2 levels is important for this operation.

PMID- 8523666
TI  - [Reevaluation of protective effect of mild hypothermia on brain ischemia
      following massive bleeding].
AB  - Mild hypothermia was speculated to have protected the brain from ischemic damage
      attributed to hypotension in two patients who had suffered massive bleeding. One
      patient developed hypotension below 40 mmHg of systolic pressure for 2 hr 30 min
      during hemi-hepatectomy. The patient's body temperature fell spontaneously to 31
      degrees C and was maintained at about 31 degrees C during hypotension because a
      large amount of cold blood and fluid were given. Another patient injured by
      traffic accident developed hypotension below 40 mmHg of systolic pressure for 30
      min. The patient was placed in hypothermic state of 33 degrees C by surface
      cooling immediately after induction of anesthesia. After the completion of
      surgery, no neurological deficit was found in either patient. Mild hypothermia is
      a useful and valuable method for protecting the brain during accidental profound
      hypotension.

PMID- 8523667
TI  - [Effects of selective radicular block for reflex sympathetic dystrophy].
AB  - We have analyzed therapeutic effects of selective radicular block for 30 patients
      of reflex sympathetic dystrophy with residual intractable pain after neurolytic
      sympathetic ganglion blockade. Ten patients showed complete pain relief after the
      therapy with a effective rate of 66.7%. Minor side effects were observed in 3
      cases (10%). When examined 2 month after the therapy, the effect had persisted in
      16 cases in successful 20 cases. The therapy could not relieve complaints induced
      by numbness and neuroma. By the therapy, patients with diffuse pain were more
      comfortable than patients with regional pain. In indicated cases, this therapy is
      useful for residual complain of reflex sympathetic dystrophy after neurolytic
      sympathetic ganglion block.

PMID- 8523668
TI  - [Anesthetic experiences in 3 patients with multiple myeloma].
AB  - Multiple myeloma which occurs mostly in aged people is a neoplastic proliferation
      of plasma cells characterized by immunoglobulin disorders. It presents various
      kinds of signs and complications depending on its stage and involved organs, and
      these complications often require surgical treatment. Risk factors to be
      considered include renal failure, hemorrhagic tendency, increased susceptibility
      to infections, hyperviscosity syndrome, anemia, and hypercalcemia. We report 5
      anesthetic experiences in 3 cases with multiple myeloma.

PMID- 8523669
TI  - [Difficult adult airway and endotracheal intubation].
AB  - In 1984, Cormack and Lehane defined laryngoscopic view in four grades. As the
      view worsens, the difficulty of intubation may increase but it is not clear. In
      this study, we examined the endotracheal intubation techniques to the grade III
      or IV airways. Some 48 patients were determined as grade III and IV. In 26
      patients the conventional endotracheal intubation technique (conventional
      technique) was selected. In 20 patients endotracheal intubation was performed
      over the gum-elastic bougie (bougie technique). In two patients laryngeal mask
      airway, fiberoptic bronchoscope and handmade flexible guide tube were used as
      aids to endotracheal intubation (guide technique). Nineteen patients with
      conventional technique and 6 patients with bougie technique required the external
      laryngeal pressure. In conclusion, the grade III or IV airways were not always
      difficult to intubate. But when the conventional technique failed, the gum
      elastic bougie or laryngeal mask airway was a fairly useful aid to endotracheal
      intubation. Moreover our handmade flexible guide tube made the intubation through
      the laryngeal mask airway safe and reliable.

PMID- 8523818
TI  - Intratumoral heterogeneity of hst-1 gene amplification in esophageal carcinoma
      with reference to DNA stem line heterogeneity.
AB  - Amplification of the hst-1 gene was examined in 112 neoplastic lesions from 27
      patients with esophageal carcinoma. Ninety specimens were separately obtained
      from two or more sections of each individual primary tumor with DNA stem line
      heterogeneity and 22 specimens were obtained from metastatic lymph node lesions.
      The assessment was that hst-1 gene amplification within each individual primary
      tumor was identical in all 27 cases (100%) and that the intensity of
      amplification in the primary tumor matched that in the metastatic lesion in 18 of
      22 cases (82%). When we examined 33 endoscopic biopsy specimens from esophageal
      carcinoma in the same manner, the intensity of hst-1 gene amplification in the
      specimens was similar to that obtained in surgical specimens from 26 of the 33
      patients (79%). These results suggest that hst-1 gene amplification might occur
      in a homogeneous manner as a relatively early genetic event prior to lymph node
      metastasis, and that therefore, prior to surgical treatment, it can be evaluated
      from a single biopsy specimen.

PMID- 8523819
TI  - FUS/TLS-CHOP chimeric transcripts in liposarcoma tissues.
AB  - Myxoid liposarcoma and malignant fibrous histiocytoma (MFH) are common soft
      tissue sarcomas of adulthood. Histopathologically they often show intratumor
      heterogeneity. In some cases, differential diagnosis of liposarcoma and MFH is
      difficult. It has been reported that myxoid liposarcomas are characterized by
      chromosomal translocation t (12; 16) (q13; p11), and that this results in two
      types (type I and type II) of FUS/TLS-CHOP fusion transcripts. In this study, the
      FUS/TLS-CHOP chimeric transcripts in seven malignant soft tissue tumors of Asian
      patients were analyzed by reverse transcription-polymerase chain reaction, DNA
      blot hybridization and nucleotide sequencing. One myxoid liposarcoma and two
      round cell liposarcomas possessed a chimeric transcript whose fusion point was
      the same as that of the type I fusion transcript reported previously for myxoid
      liposarcoma. We were thus able to detect the type I FUS/TLS-CHOP fusion
      transcript in clinical specimens of liposarcoma from Asian patients, including
      the first examples of round cell liposarcoma. These results suggest that the
      detection of FUS/TLS-CHOP chimeric transcripts or chimeric genes can be used as a
      diagnostic tool for the pathological diagnosis of liposarcomas.

PMID- 8523820
TI  - Association of epidermal growth factor-related peptides and type I receptor
      tyrosine kinase receptors with prognosis of human colorectal carcinomas.
AB  - The frequency of expression and localization of cripto-1 (CR-1), amphiregulin
      (AR), transforming growth factor alpha (TGF alpha), epidermal growth factor
      receptor (EGFR) and erbB-2 were examined by immunohistochemistry in 45 carcinomas
      and adjacent non-involved normal colon mucosa. Thirty (66.7%), 24 (53.3%), 23
      (51.1%), 23 (51.1%) and 13 (28.9%) of the 45 carcinomas showed positive staining
      for CR-1, AR, TGF alpha, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17
      (37.7%), 15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involved
      normal mucosa specimens were reactive. Among 13 carcinomas with lymph node
      involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8 (61.5%) and 7 (53.8%) exhibited
      positive staining for CR-1, AR, TGF-alpha, EGFR and erbB-2, respectively. There
      was a statistically significant association between the frequency of either TGF
      alpha (P < 0.05) or erbB-2 (P < 0.05) expression and lymph node metastasis. In
      addition, a significantly higher frequency of positive staining for TGF alpha was
      observed in Dukes' grade C carcinomas (P < 0.05). Finally, significant trends for
      coexpression of EGFR and either TGF alpha (P < 0.01) or AR (P < 0.05) were
      detected in carcinomas. These data suggest that AR and TGF alpha may play an
      important role in the development of colorectal carcinomas through an autocrine
      mechanism involving EGFR, and demonstrate that TGF alpha and erbB-2 may be more
      reliable indicators of metastasis or prognosis than CR-1, AR or EGFR in human
      colon cancers.

PMID- 8523822
TI  - Radiotherapy for laryngeal cancer in patients under 50 years old.
AB  - Fifty-nine cases of laryngeal cancer treated by radiotherapy at the National
      Cancer Center Hospital between 1962 and 1990 were analyzed retrospectively. All
      the patients were less than 50 years old. The median total dose of the radiation
      delivered to the primary tumor site was 70 Gy. The overall 5-yr survival rate and
      5-yr local control rate were 88% and 72%, respectively. Five (8.5%) of the 59
      patients developed late recurrence more than five yr after initial treatment, but
      subsequent salvage operations were successful for disease control; three patients
      had T1 glottic cancer, one had T2-3 glottic cancer and one had T3N1 supraglottic
      cancer. Since the local control rate and the 5-yr survival rate after
      radiotherapy are satisfactory, radiotherapy, which allows both functional and
      esthetic conservation, has an important role in the treatment of laryngeal cancer
      in adults under 50 yr of age.

PMID- 8523821
TI  - Comparison of peripheral blood stem cells mobilized with granulocyte colony
      stimulating factor with or without prior standard-dose chemotherapy in patients
      with malignancy.
AB  - We studied the effect of granulocyte colony-stimulating factor on the magnitude
      of peripheral blood stem cell mobilization in patients with malignancy. The
      leukapheresis products mobilized with granulocyte colony-stimulating factor alone
      at a steady state (a period of full hematopoietic recovery) (group 1) were
      compared with those obtained after cytotoxic chemotherapy using granulocyte
      colony-stimulating factor (group 2). In group 1, six patients underwent six
      courses of stem cell collection with a median of 20 l leukapheresis. In group 2,
      10 patients underwent 12 courses of stem cell collection with a median of 10 l
      leukapheresis. Median yields of group 1 vs. group 2 were mononuclear cells (x
      10(9)), 21.9 vs. 11.6; CD34+ cells (x 10(6)/l), 14.5 vs. 17.1; colony-forming
      unit for granulocyte-macrophage (/ml), 223 vs. 1193; burst-forming unit for
      erythroid (/ml), 29 vs. 71; colony-forming unit for erythroid (/ml), 42 vs. 29;
      colony-forming unit for megakaryocyte (/ml), 26 vs. 59. While there were no
      statistically significant differences in the number of CD34+ cells between the
      two groups, granulocyte-macrophage-committed progenitor cells were more enriched
      in the apheresis products of group 2. The correlation between CD34+ cells and
      colony-forming unit for granulocyte-macrophage was poor. Our results demonstrate
      that granulocyte colony-stimulating factor can mobilize a sufficient number of
      progenitor cells into the peripheral blood for stem cell transplantation with or
      without prior chemotherapy.

PMID- 8523823
TI  - Concurrent chemotherapy and radiation therapy for locally advanced carcinoma of
      the esophagus.
AB  - A pilot study was undertaken to clarify the efficacy of concurrent
      chemoradiotherapy against locally advanced esophageal carcinoma. The 20 patients
      in this study had previously untreated esophageal carcinoma with evidence of T4
      disease and/or distant node metastases. Chemotherapy consisted of protracted
      infusion of 5-fluorouracil at a dose of 400 mg/m2/day on days 1-5 and 8-12,
      combined with a 2-h infusion of cisplatinum at 40 mg/m2 on days 1 and 8.
      Radiation treatment for the mediastinum was administered 5 days per week for 3 wk
      at 2 Gy/day, along with chemotherapy. These schedules were repeated twice to give
      a total radiation dose of 60 Gy. For patients who responded, two additional
      courses of chemotherapy were administered. Five of the 20 patients had UICC stage
      III disease and 15 had stage IV. Seventeen (85%) of the 20 patients exhibited an
      objective response, including 6 (30%) complete responses. Local control was
      excellent with 10 (50%) complete responses. Toxic effects were severe. Major
      toxicities were leukocytopenia of grade 3 or more in 45% of the patients and
      esophagitis, including four perforations. There were two treatment-related
      deaths. The median survival time was 9 mo (range: 2 to 34+). Concurrent
      chemotherapy and radiotherapy was effective even for locally advanced esophageal
      carcinoma, but was associated with significant toxicity.

PMID- 8523824
TI  - The confusion associated with breast cancer chemotherapy in Japan: the first
      year's experience at the Division of Oncology and Hematology, National Cancer
      Center Hospital East.
AB  - The current status of breast cancer chemotherapy in Japan was examined and
      compared with internationally accepted standard therapy, by reviewing the
      previous treatment of patients with advanced or metastatic breast cancer who had
      been referred to the National Cancer Center Hospital East. Forty patients were
      referred mainly from middle-sized or large hospitals between July 1992 and June
      1993. The most commonly used regimen for adjuvant therapy was a combination of
      long-term and oral low-dose fluoropyrimidine compounds (LDFU), which is rarely
      used in Western countries, and tamoxifen. Some patients had received
      perioperative intravenous mitomycin C. The adjuvant polychemotherapy most
      commonly used internationally has been given to only a few patients. The first
      line treatment for advanced or metastatic disease in the previous hospitals
      varied, but myelosuppressive chemotherapy including anthracyclines was given to
      half of the patients. Oral LDFU was also used for some patients alone or in
      combination as the first-line chemotherapy. Local therapy for metastasis to soft
      tissue was performed in 9 patients. Oral LDFU therapy that is frequently used for
      cancer treatment in Japan should be evaluated in a well designed controlled
      trial.

PMID- 8523825
TI  - Malignant rhabdoid tumor of the breast: a case report.
AB  - A 66-year-old woman developed a malignant rhabdoid tumor of the breast, with a
      tumor doubling time of 10 days. One month after radical mastectomy, there was
      local recurrence, followed by multiple pulmonary metastases, and the patient died
      of respiratory failure 5 months after surgery. The gray-white-colored tumor
      measured 13 x 12 x 10 cm, and its border was well defined. The tumor was composed
      of diffusely growing round or polygonal cells with vesicular nuclei, prominent
      nucleoli, and ample cytoplasm containing eosinophilic inclusions. Lymph node
      involvement was widespread. Both vimentin and keratin were clearly demonstrated
      by immunohistochemical staining. Ultrastructural studies revealed that the MRT
      cells contained cytoplasmic whorls of intermediate filaments.

PMID- 8523826
TI  - Pulmonary epithelioid hemangioendothelioma: a case report.
AB  - A 45-year-old woman whose x-ray film revealed multiple widespread bilateral small
      nodules was diagnosed as having pulmonary tuberculosis or metastatic pulmonary
      cancer. A conclusive histological diagnosis of pulmonary epithelioid
      hemangioendothelioma (PEH) was made following an open-lung biopsy. PEH is a
      progressive disease that probably originates from an endothelial cell. However,
      there is still no effective therapeutic modality for PEH. The postoperative
      course of our patient has been uneventful with no evidence of tumor growth for
      four and a half years after initial x-ray detection of the lesions.

PMID- 8523827
TI  - Surgical management for lymph node recurrence of resected fibrolamellar carcinoma
      of the liver: a case report.
AB  - Fibrolamellar carcinoma of the liver (FLC), which is very rare in Japan, is
      reported to be frequently accompanied by lymph node metastasis in Europe and the
      United States. We describe a 22-year-old man with recurrent FLC in the lymph
      nodes after undergoing partial hepatectomy. He underwent a second operation for
      removal of recurrent lymph node tumors in the mediastinum and abdominal cavity
      one year after initial surgery. However, a third operation became necessary seven
      months later, because of recurrence in a lymph node in the abdominal cavity. We
      discuss the management of lymph node metastasis from FLC.

PMID- 8523828
TI  - [Clinical implications of mismatched uptakes of beta-methyl fatty acid analogue
      and thallium in infarcted myocardium: correlations with coronary stenosis and
      regional wall motion abnormality].
AB  - Myocardial perfusion and fatty acid metabolism were assessed by using myocardial
      single-photon emission computed tomography with thallium and beta-methyl-p
      iodophenyl-pentadecanoic acid (BMIPP) during acute and/or late stages of
      myocardial infarction in 157 infarcted segments of 100 patients. The incidence of
      reduced thallium perfusion relative to BMIPP uptake ("T-type" mismatch) was
      significantly (p < 0.05) lower (9%) compared to that of reduced BMIPP uptake
      relative to thallium perfusion ("B-type" mismatch) (59%) or non-mismatched
      segment (32%). In an anteroseptal region, B-type dissociation had a significantly
      higher incidence compared to no or T-type mismatch; 68% vs. 27% vs. 5%,
      respectively, whereas the incidence of T-type uptake was relatively high in
      inferior and posterolateral regions; 13%, 11%, respectively. Severe coronary
      stenosis was observed in 76% of B-type segments and 72% of non-mismatched
      segments but in only 43% of T-type segments. The incidence of regional wall
      motion abnormality was significantly lower (46%) in the T-type mismatch segments
      when compared to the B-type (91%) or non-mismatched segments (96%). In
      conclusion, myocardial fatty acid metabolism was more markedly impaired compared
      to an involved coronary perfusion, resulting in the mismatch of perfusion and
      fatty acid metabolism. Coronary stenosis and regional wall motion abnormality are
      more closely related to "B-type" mismatch but not necessarily to "T-type"
      dissociation, probably because of attenuation artifacts in inferior and
      posterolateral regions in thallium scan.

PMID- 8523829
TI  - [Medical image transmission via communication satellite: evaluation of bone
      scintigraphy].
AB  - As compared with terrestrial circuits, the communication satellite possesses
      superior characteristics such as wide area coverage, broadcasting, high capacity,
      and robustness to disasters. Utilizing the narrow band channel (64 kbps) of the
      geostationary satellite JCSAT1 located at the altitude of 36,000 km above the
      equator, the authors investigated satellite-relayed medical images by video
      signals, with bone scintigraphy as a model. Each bone scintigraphy was taken by a
      handy-video camera, digitalized and transmitted from faculty of technology
      located at 25 kilometers apart from our department. Clear bone scintigraphy was
      obtained via satellite, as seen on the view box. Eight nuclear physicians
      evaluated 20 cases of bone scintigraphy. ROC (Receiver Operating Characteristic)
      analysis was performed between the scintigraphies on view box and via satellite
      by the rating method. The area under the ROC curve was 91.6 +/- 2.6% via
      satellite, and 93.2 +/- 2.4% on the view box and there was no significant
      difference between them. These results suggest that the satellite communication
      is very useful and effective system to send nuclear imagings to distant
      institutes.

PMID- 8523830
TI  - [Mechanism of overshoot elevation of left ventricular ejection fraction during
      recovery after exercise in normal subjects and patients with coronary artery
      disease, assessed by 99mTc exercise radionuclide ventriculography].
AB  - An "overshoot" (OS) elevation of ejection fraction above resting levels has been
      demonstrated during recovery after exercise. To characterize the hemodynamic
      changes during recovery after bicycle exercise, we used radionuclide
      ventriculography under the Swan-Ganz catheter insertion in 16 normal subjects and
      15 patients with coronary artery disease (CAD) at rest, during bicycle exercise
      and after exercise periods. In normal subjects, the ejection fraction increased
      from resting value during peak exercise, and showed overshoot elevation in the
      early recovery period. In patients with CAD, the ejection fraction decreased from
      resting value during peak exercise, then showed overshoot elevation in the early
      recovery period. In normal subjects, the end-diastolic volume (EDV) and the end
      systolic volume (ESV) decreased from resting value during OS. In patients with
      CAD, the EDV at OS was not different from that at rest, the ESV decreased from
      resting value during OS. The systemic vascular resistance increased from resting
      value during OS. The systolic blood pressure/ESV, index for ventricular
      contractility, increased from resting value during OS in both groups. Thus, the
      decreased systemic vascular resistance does not playing a major role during
      recovery after exercise, whereas enhanced contractility is evident in both normal
      subjects and patients with CAD.

PMID- 8523831
TI  - [Detection of myocardial 123I-BMIPP distribution abnormality in patients with
      ischemic heart disease based on normal data file in bull's-eye polar map].
AB  - Visual interpretation of 123I-BMIPP (BMIPP) myocardial images has difficulties in
      detecting mild reduction in tracer uptake. We studied the significance of the
      objective assessment of myocardial BMIPP maldistributions at rest by using a
      Bull's-eye map and its normal data file for detecting ischemic heart disease.
      Twenty nine patients, 15 with prior myocardial infarction and 14 with effort
      angina were studied. The initial 15-min BMIPP image was evaluated by visual
      analysis and by generating the extent Bull's-eye map which exhibits regions with
      reduced % uptake under mean-2SD of 10 normal controls. The sensitivity for
      determining coronary lesions in non-infarcted myocardial regions with the extent
      map was superior to that with visual analysis (67% vs. 33%). In the regions
      supplied by the stenotic coronary artery, those which showed visually negative
      but positive in the map and which showed positive in both had higher incidence of
      wall motion abnormalities and severe coronary stenosis than those with normal
      findings in both. These results suggest that the objective assessment based on
      the normal data file in a Bull's-eye polar map is clinically important for
      improving the limitation of the visual interpretation in 123I-BMIPP imaging.

PMID- 8523832
TI  - [Assessment of myocardial fatty acid metabolism in patients with vasospastic
      angina using 123I-BMIPP myocardial SPECT].
AB  - Myocardial perfusion and fatty acid metabolism may be unpaired in the patients of
      vasospastic angina (VSA), because abnormal regional wall motion of left ventricle
      has been shown in some cases of VSA without apparent history of myocardial
      infarction. To study the clinical utility of 123I-BMIPP scintigraphy in diagnosis
      of myocardial ischemia in VSA, both 123I-BMIPP (rest) and 201T1 (exercise) SPECT
      were performed in the 20 patients of VSA diagnosed by coronary angiography.
      Defect scores were calculated visually from the 17 segments of myocardial images
      and were compared with patient's anginal history, period from last attack,
      numbers of attack, left ventricular (LV) ejection fraction and severity of
      regional LV wall motion abnormality. 123I-BMIPP SPECT images showed decreased
      tracer uptake in 14 cases of 20 (70%) VSA patients. Exercise 201T1 SPECT images
      showed decreased tracer uptake in 3 cases of 20 (15%) of patients. Severity of
      regional LV wall motion abnormality was correlated with defect score of BMIPP.
      Though total defect score of BMIPP did not correlate with patient's anginal
      history, number of symptoms and LV ejection fraction, correlated inversely with
      period from last attack. It was suggested that 123I-BMIPP myocardial SPECT images
      in VSA patients showed "memories" of myocardial ischemic damages induced by
      vasospasm. In summary, 123I-BMIPP myocardial SPECT images could be a useful test
      for diagnosis and evaluation of VSA.

PMID- 8523833
TI  - [A case of hypertensive hypertrophy in which both regression of hypertrophy and
      improvement of the abnormalities in iodine-123-metaiodobenzylguanidine (MIBG)
      myocardial imagings were observed after antihypertensive therapy].
AB  - A case of hypertensive hypertrophy is described in which both regression of
      hypertrophy and improvement of the abnormalities in iodine-123
      metaiodobenzylguanidine (MIBG) myocardial imagings were seen after 7 months of
      antihypertensive therapy. A 58-year-old man was diagnosed as having essential
      hypertension and hypertensive hypertrophy. The patient was treated with
      antihypertensive drugs and showed regression of left ventricular hypertrophy on
      electrocardiograms and echocardiograms. MIBG observations made before and after
      antihypertensive therapy showed increased heart-to-mediastinum activity ratio and
      decreased cardiac washout ratio. Despite the many theories addressing the
      mechanisms of regression of left ventricular hypertrophy, the process is still
      unclear. In the present case, the improvement of cardiac sympathetic nervous
      dysfunction might have been related to the regression of left ventricular
      hypertrophy because the abnormality in MIBG images improved. MIBG, therefore, may
      be helpful in clarifying the mechanisms of the regression of hypertensive
      hypertrophy.

PMID- 8523834
TI  - [123I-MIBG myocardial SPECT in two patients with familial amyloid
      polyneuropathy].
AB  - 201T1C1 SPECT and 123I-MIBG SPECT were performed in two patients with familial
      amyloid polyneuropathy (FAP). Both patients showed normal accumulation of 201T1C1
      and no accumulation of 123I-MIBG in the myocardium at the early and delayed
      images. These results indicate that the patient with FAP-related myocardial
      change accompanies sympathetic nerve dysfunction. The dysfunction is supposed to
      be caused by disturbance of re-uptake of MIBG by the terminal ending of the
      sympathetic nerve (uptake-1) through the amyloid-deposited connective tissue.

PMID- 8523835
TI  - [Experience with mild exercise 123I-BMIPP myocardial imaging in two cases of
      ischemic heart disease].
AB  - During mild to moderate ischemia, glycolytic flux is enhanced and free fatty acid
      uptake is reduced in proportion to the reduction in mitochondrial metabolism. We
      considered that mild exercise may induce the reduction of 123I-BMIPP, reflecting
      myocardial fatty acid metabolism, in ischemic myocardium compared to normal
      myocardium. Therefore, mild exercise 123I-BMIPP myocardial imaging was carried
      out to detect myocardial ischemia in 2 cases of ischemic heart disease. Mild
      exercise was performed using a bicycle ergometer with 25-50 W loading. At seven
      minutes before cessation of exercise, 111 MBq of 123I-BMIPP was injected. Case 1
      was a 12 year-old boy with Kawasaki's disease. The study showed a reduction of
      mild exercise 123I-BMIPP uptake in the anteroseptal wall. In contrast, stress
      201T1 myocardial imaging did not show perfusion defect in the anteroseptal wall.
      Case 2 was a 64 year-old female with triple vessels disease. Mild exercise 123I
      BMIPP myocardial imaging showed similar with those of stress 99mTc-sestamibi. We
      conclude that mild exercise 123I-BMIPP myocardial SPECT may be a sensitive method
      to detect myocardial ischemia.

PMID- 8523836
TI  - [Current status of nuclear oncology in Japan].
AB  - The most commonly used radionuclides for cancer patients in Japan have been still
      67Ga and 201T1 chloride. In addition to the diagnosis of lung cancer and thyroid
      tumor, 201T1 is recently applied to patients with brain tumor, bone and soft
      tissue tumor and parathynoid adenoma. Comparing to Nuclear Cardiology and Brain
      Nuclear Medicine, where many new radiopharmaceuticals have been developed, there
      are few new drugs in Nuclear Oncology. In other words, new radiopharmaceuticals
      are expected to be developed for the diagnosis and/or therapy of cancer. In
      addition to 131I for thyroid cancer, new radiopharmaceuticals such as 111In
      octreotide and 99mTc(V)-DMSA have been clinically employed. In spite of strong
      expectation, radiolabeled monoclonal antibodies have not been clinically used in
      Japan. However, the technique of humanized antibodies has been established and in
      U.S.A., 131I-labeled antibodies are reported to be effective for the treatment of
      malignant lymphoma. 89Sr is useful for the relief of bone pain caused by the bone
      metastasis. New findings that SPECT of 18F-FDG, a positron emitter, has been
      revealed to have a great potential in the management of cancer patients, will
      give a great impact on Nuclear Oncology.

PMID- 8523837
TI  - [Clinical application of 99mTc-tetrofosmin myocardial SPECT--a multicenter
      trial].
AB  - We performed a multicenter trial of 99mTc-tetrofosmin myocardial SPECT for the
      assessment of acute thrombolysis, pre and post elective PTCA and myocardial
      viability in comparison with 201Tl myocardial SPECT. The participants consisted
      of 212 patients at 44 institutions and the study lasted for 10 months. In
      assessing acute thrombolysis, the perfusion defect from the acute to subacute
      phase was reduced by 25% and that from the subacute to chronic phase by 10%. The
      mean perfusion defect score at subacute and chronic phase was correlated well
      with regional wall motion. The mean defect score during the subacute phase could
      predict future wall motion abnormalities. In assessing pre and post PTCA, 99mTc
      tetrofosmin stress/rest myocardial SPECT could identify the changes of perfusion
      as in the case with successful PTCA and/or restenosis. In assessing the
      myocardial viability, 99mTc-tetrofosmin rest myocardial SPECT was superior to
      201Tl redistribution, and equal to 201Tl reinjection method. In summary, we
      concluded that 99mTc-tetrofosmin is a powerful tool, with which to diagnose and
      manage patients with coronary artery diseases.

PMID- 8523838
TI  - [123I-metaiodobenzylguanidine myocardial scintigraphy in a case of
      pheochromocytoma before and after resection of it].
AB  - A 55-year-old man with pheochromocytoma was examined by 123I
      metaiodobenzylguanidine (MIBG) myocardial scintigraphy before and after resection
      of the tumor. MIBG images showed decreased uptake in infero-posterior wall before
      operation. The heart to upper mediastinum uptake ratio was low at the delayed
      anterior planar image, and mean MIBG clearance from the left ventricle was
      increased. These abnormal scintigraphic findings improved after resection of the
      tumor. We thought that these abnormal MIBG findings were not due to abnormal
      cardiac sympathetic nerve function, because ECG, chest X-ray, UCG and 201Tl
      myocardial scintigram did not reveal any abnormality. It may be presumed that
      these abnormal MIBG findings were caused by high plasma catecholamines
      concentration. The mechanism of abnormal MIBG findings of the heart remains
      uncertain in various heart diseases. MIBG findings in this case with
      pheochromocytoma before and after resection may contribute to interpretation of
      the kinetics of MIBG in heart.

PMID- 8523839
TI  - [Immunochemiluminometric assay (Automated Chemiluminescence System ACS: 180) for
      CEA].
AB  - We examined Automated Chemiluminescence System ACS: 180 for CEA assay, especially
      about confidence of the functional sensitivity. Serum CEA levels of normal
      subjects and patients were measured not only with ACS: 180 but also with
      immunoradiometric assay (CEA kit [Daiichi] II). Using ACS: 180 assay for CEA,
      intra-assay coefficients of variation (C.V.s) were 4.06% at 1.97 ng/ml, 1.62% at
      17.3 ng/ml, and 2.28% at 81.3 ng/ml. Interassay C.V.s were 4.02% at 1.99 ng/ml,
      1.21% at 16.5 ng/ml, and 3.44% at 79.4 ng/ml. The detection limit (functional
      sensitivity) of ACS: 180 assay for CEA was 0.4 ng/ml by the precision profile.
      The coefficient of correlation of 164 sera, which CEA values were among 0.4-100
      ng/ml (working range of ACS: 180), between with ACS: 180 and with CEA kit
      [Daiichi] II was R = 0.942, y = 1.07 x +0.09 (p < 0.05). Seven (13.2%) normal
      subjects (n = 53) and 45 (34.1%) patients with malignant diseases (n = 132) had
      higher serum CEA levels than the cut off value (2.5 ng/ml). The sera of 82
      malignant patients who had both pre- and post-operation sample were determined.
      Sixty-five patients of them were decrease after operation. These results of ACS:
      180 resembled to that of CEA kit [Daiichi] II. We conclude that ACS: 180 for CEA
      assay was precise enough to measure below the cut off value, and had good
      performance of its speed (short incubation) and convenience.

PMID- 8523840
TI  - [Pharmacokinetics of 123I-iomazenil, a benzodiazepine receptor seeker].
AB  - The biodistribution, metabolism and excretion of 123I-iomazenil have been studied
      in rats, rabbits and humans following i.v. administration. In all the species,
      123I-iomazenil was rapidly metabolized and more than 90% of the administrated
      radioactivity was excreted within the first 24 hr. Dominant metabolites were acid
      metabolite (R-COOH), glucuronide of the acid (R-COOH-Glc) and free iodide (I-) in
      rats and humans. On the other hand, R-COOH, oxidative metabolite (R'-CH2COOH) and
      I- were found in rabbits. Thus, the possible metabolic pathways of iomazenil were
      hydrolysis, oxidation, conjugation and deiodination. The radioactivity was
      excreted into both urine and feces in rats, while primary route of excretion in
      rabbits and humans was from the kidneys. At 3 hr after injection, more than 97%
      of the radioactivity in rat brain was found in the form of the parent compound.
      This result indicates that metabolites of 123I-iomazenil do not cross the blood
      brain barrier.

PMID- 8523841
TI  - [Usefulness of the 201TlCl exercise leg perfusion scintigraphy inarteriosclerosis
      obliterans (ASO)--with evaluation of leg perfusion comparing before and after
      PTA].
AB  - Twenty-eight patients of arteriosclerosis obliterans (ASO) complaining of
      intermittent claudication or pain at rest underwent symptom limited exercise leg
      perfusion scintigraphy using 201TlCl (Tl). Regions of interest (ROI) were drawn
      around each buttocks, thighs, calves and feet in whole body image, and we
      calculated Lesion/Normal Index (LNI) which was the divided value of the average
      count per pixel of each ROI of the affected side by that of the normal side. The
      average LNI of the foot was 0.81 and was smaller than other regions (p < 0.05).
      Other region except foot showed Tl high uptake in affected side in some cases.
      Fifteen patients were compared after percutaneous transluminal angioplasty (PTA)
      with before PTA, and LNI of the foot was statistically improve after PTA (p <
      0.005). The period suffer from disease of the group of Tl high uptake in the
      affected leg was statistically shorter than that of the group of Tl non-high
      uptake (p < 0.05). We supposed that the Tl uptake of the foot reflects ischemia
      of the leg sensitively, and high uptake of Tl in affected leg is concerned with
      compensatory change of microcirculation of ischemic leg in subacute period. This
      scintigraphy was thought to be useful to detect the ASO and to evaluate the
      effect of PTA, and was able to avail diagnosis and observation of the course of
      ASO patient.

PMID- 8523842
TI  - [Clinical usefulness of dipyridamole loading 99mTc-tetrofosmin myocardial
      scintigraphy].
AB  - This study performed to establish the most suitable method in one-day protocol
      and to evaluate clinical usefulness of 99mTc-tetrofosmin myocardial scintigraphy
      after dipyridamole infusion. Image quality and liver overlapping of the
      myocardial SPECT were evaluated in 107 patients with old myocardial infarction
      (42 cases), angina pectoris (53 cases) and others (12 cases). Left ventricular
      wall motion and coronary artery stenosis were compared to myocardial uptake score
      in 55 patients who received cardiac catheterization. The suitable image quality
      was acquired in early SPECT images using 259 MBq of 99mTc-tetrofosmin. The
      overlapping between inferior wall and liver uptake was able to minimize over 45
      minutes interval from injection of 99mTc-tetrofosmin to data acquisition. The
      segments of normal wall motion had no perfusion defect of the myocardial SPECT in
      all cases (100% (148/148)). The segments of abnormal wall motion had decreased
      myocardial uptake of the myocardial SPECT (77% (24/31)). The agreement between
      coronary artery stenosis and decreased myocardial uptake was 96% (24/25) in right
      coronary artery, 87% (26/30) in left anterior descending coronary artery and 83%
      (19/23) in left circumflex coronary artery. These data suggests that image
      quality of dipyridamole loading 99mTc-tetrofosmin myocardial scintigraphy.
      Myocardial perfusion in the 99mTc-tetrofosmin myocardial scintigraphy is good
      correlation to both left ventricular wall motion and coronary artery stenosis.

PMID- 8523843
TI  - [Diagnostic usefulness of myocardial SPECT with 123I-beta-methyl-iodophenyl
      pentadecanoic acid and 201Tl in unstable angina].
AB  - The purpose of this study is whether 123I-BMIPP detects a culprit lesion in
      patients with unstable angina. Twenty-six patients with unstable angina underwent
      123I-BMIPP (BMIPP) and 201Tl (Tl) imaging at rest. BMIPP image was compared with
      Tl imaging. BMIPP imaging revealed defects or low uptake corresponding to
      myocardial ischemic areas predicted by coronary angiography in 19 (73.1%) of 26
      patients. Tl imaging showed defects or low uptake corresponding to coronary
      angiographic findings in 14 (53.8%). BMIPP demonstrated significantly less uptake
      than Tl (p = 0.001). Severity of reduced BMIPP activity was greater than that of
      Tl (p < 0.001). We concluded that BMIPP imaging was excellent to detecting of
      culprit lesions in patients with unstable angina. BMIPP SPECT is a sensitive
      method for detecting myocardium exposed to transient schemia that cannot be
      detected by Tl imaging.

PMID- 8523844
TI  - [Effect of scatter correction on quantification of myocardial SPECT and
      application to dual-energy acquisition using triple-energy window method].
AB  - Triple-energy window (TEW) method is a simple and practical approach for
      correcting Compton scatter in single-photon emission tracer studies. The fraction
      of scatter correction, with a point source or 30 ml-syringe placed under the
      camera, was measured by the TEW method. The scatter fraction was 55% for 201Tl,
      29% for 99mTc, 57% for 123I. Composite energy spectra were generated and
      separated by the TEW method. Combination of 99mTc and 201Tl was separated well,
      and 201Tl and 123I were separated within an error of 10%; whereas asymmetric
      photopeak energy window was necessary for separating 123I and 99mTc. By applying
      this method to myocardial SPECT study, the effect of scatter elimination was
      investigated in each myocardial wall by polar may and profile curve analysis. The
      effect of scatter was higher in the septum and the inferior wall. The count ratio
      relative to the anterior wall including scatter was 9% higher in 123I, 7-8%
      higher in 99mTc and 6% higher in 201Tl. Apparent count loss after scatter
      correction was 30% for 123I, 13% for 99mTc and 38% for 201Tl. Image contrast, as
      defined myocardium-to-left ventricular cavity count ratio, improved by scatter
      correction. Since the influence of Compton scatter was significant in cardiac
      planar and SPECT studies; the degree of scatter fraction should be kept in mind
      both in quantification and visual interpretation.

PMID- 8523845
TI  - [Normal cerebral perfusion of 99mTc-HMPAO brain SPECT--evaluation by ananatomical
      standardization technique].
AB  - Single photon labeled tracer 99mTc-hexamethylpropylene amine oxime (HMPAO) has
      been used for rCBF studies by SPECT. However, normal perfusion pattern of this
      agent still remains unclear. The purpose of this study was to investigate normal
      99mTc-HMPAO SPECT image voxel by voxel. Eighteen male subjects without any prior
      or present history of medical illness participated in this study. All SPECT
      images were globally normalized to 100 count/voxel. Each subject had an X-ray CT
      scan at the same day of SPECT measurement. All subjects had normal X-ray CT
      scans. The standard anatomical structures of the computerized brain atlas of
      Roland et al. were fitted to X-ray CT images of a subject by linear and non
      linear parameters. These parameters were subsequently used to transform SPECT
      images of the subject. After the anatomical standardization, mean and SD images
      of eight standardized images were calculated voxel-by-voxel basis. In the mean
      image, following structures showed relatively higher radioactivity; the putamen,
      the cerebellum, and the frontal lobe. In addition, the occipital lobe, parietal
      lobe, frontal lobe, and the putamen showed large degree of SD. Anatomical
      standardization of SPECT images may be useful as a reference to diagnose and
      evaluate various brain disorders.

PMID- 8523846
TI  - [Local cerebral blood flow and glucose metabolism during seizure in spontaneously
      epileptic El Mice].
AB  - Local cerebral blood flow and glucose metabolism were examined in spontaneously
      epileptic El mice using autoradiography with 125I-IMP and 14C-DG in the
      interictal phase and during seizure. El (+) mice that developed generalized tonic
      clonic convulsions and El (-) mice that received no stimulation and had no
      history of epileptic seizures were examined. The seizure non-susceptible,
      maternal strain ddY mice were used as control. Uptake ratios for IMP and DG in
      mouse brain were calculated using the autoradiographic density. In the interictal
      phase, the pattern of local cerebral blood flow of El (+) mice was similar to
      that of ddY and El (-) mice, and glucose metabolism in the hippocampus was higher
      in El (+) mice than in El (-) and ddY mice, but flow and metabolism were nearly
      matched. During seizure, no significant changed blood flow and increased glucose
      metabolism in the hippocampus, the epileptic focus, and no markedly changed blood
      flow and depressed glucose metabolism in other brain regions were observed and
      considered to be flow-metabolism uncoupling. These observations have never been
      reported in clinical or experimental studies of epilepsy. Seizures did not cause
      large regional differences in cerebral blood flow. Therefore, only glucose
      metabolism is useful for detection of the focus of secondary generalized seizures
      in El mice, and appeared possibly to be related to the pathophysiology of
      secondary generalized epilepsy in El mice.

PMID- 8523847
TI  - [Investigation of discrepancy between 99mTc-HMPAO and 133Xe rCBF SPECT; a
      comparative study with X-ray CT findings].
AB  - To investigate the discrepancy between 99mTc-hexamethylpropyleneamine oxime
      (HMPAO) and 133Xe rCBF SPECT, the findings of thirty patients with reasonable
      rCBF reduction on 133Xe SPECT were compared with HMPAO SPECT and X-ray CT. The
      subjects did not include the cases of acute and subacute CVD. Both SPECT were
      performed within two weeks by ring-type dynamic SPECT (HEADTOME, Simadzu, Japan).
      In comparison between the SPECT findings by 133Xe and 99mTc-HMPAO, the subjects
      were classified into three groups as follow. Group A: Similar findings in the
      both SPECT were noted in 6 cases (20%). Group B: Smaller findings on HMPAO SPECT
      than that by 133Xe were in 11 cases (37%). Group C: No findings of rCBF reduction
      on HMPAO SPECT were in 13 cases (43%). The rCBF of the lesion measured by 133Xe
      SPECT in the group C was 24-35 ml/100 g/min. The density of HMPAO in the lesion
      did not correlate with the rCBF value. Only the severity of CT findings tend to
      correlate with the density of HMPAO. These results suggest that the reduction of
      HMPAO density depends directly on some kind of neural injury rather than the rCBF
      value. The injury may be caused by the flow reduction under the threshold of each
      neural cell. So the correlation between HMPAO density and actual rCBF might show
      like sigmoid curve. Then the HMPAO SPECT might directly reflect the regional
      extraction and fixation ratio, and the reduction of blood flow cause the minute
      neural-injury in the lesion of moderately reduced rCBF.

PMID- 8523848
TI  - [Efficacy of simultaneous function and perfusion imaging on 99mTc-tetrofosmin
      myocardial scintigraphy].
AB  - The aim of this study was to determine whether the diagnosis for coronary artery
      disease (CAD) with 99mTc-tetrofosmin (Tf) myocardial scintigraphy was improved by
      the combination of function image and perfusion image as compared with perfusion
      alone. Tf myocardial scintigraphy was performed with one-day protocol
      (stress/rest) in 51 patients (CAD: 32, Non-CAD: 19) without previous myocardial
      infarction. Function image was obtained by first pass method, and perfusion image
      by SPECT. Number of diseased vessels was 14 in right coronary artery (RCA), 18 in
      left anterior descending (LAD), and 12 in left circumflex (LCX). Ischemia was
      diagnosed by 2 different parameters 1) perfusion image alone, 2) combination of
      perfusion image and regional ejection fraction (rEF). On perfusion image,
      accuracy was 53%, 94% and 86% in RCA, LAD, and LCX respectively. On perfusion +
      rEF, accuracy was 76%, 90% and 84% in RCA, LAD, and LCX respectively. Specificity
      in RCA was 45% on perfusion, 84% on perfusion + rEF. Sensitivity in RCA was 77%
      on perfusion, 54% on perfusion + rEF. LAD and LCX did not change by the addition
      of function image. By addition of function image, accuracy and specificity of
      diagnosis in area of RCA improved significantly (p < 0.01). Thus the addition of
      function image in Tf myocardial scintigraphy would be useful to improve the
      diagnosis, especially in region of RCA.

PMID- 8523849
TI  - [Contamination of flexible fiberoptic bronchoscopes with Mycobacterium chelonae
      linked to an automated endoscope disinfection machine--on the relationship
      between the presence of the organism in the intestinal tract and contamination of
      disinfection machine, and a case of gallbladder and bile duct infection with M.
      chelonae].
AB  - In 1993, thirteen strains (8.7%) of M. chelonae were isolated from
      bronchoalveolar lavage fluid (BALF) obtained by bronchoscopy of 150 patients in
      Tachikawa-sogo (T) hospital, where the same automated disinfection machine was
      commonly used for cleaning, sterilization and disinfection of fiberbronchoscope
      and fibercolonoscope except 3 bronchoscopes disinfected by gas sterilization.
      Since January 1994, manual cleaning and sterilization has been applied for
      bronchoscope, and thereafter no strain of M. chelonae was isolated from BALF of
      55 patients in the T hospital. While only one strain (3%) of M. chelonae was
      isolated from BALF of 33 patients in Ota (O) hospital, but many strains of M.
      chelonae were isolated from intestinal fluid obtained by fibercolonoscopy of the
      patients. Manual method of cleaning and disinfection was performed for both
      bronchoscopes and colonoscopes in the O hospital from the beginning. Based on
      these results, it was suggested that M. chelonae are commonly present in the
      colon (intestine) of normal persons. Thus colonoendscope may be often
      contaminated with the organism and subsequently the automated disinfecting
      machine may also be contaminated with the organism which is resist and against
      usual disinfection procedure, and resulted in bronchoscope contamination. If the
      presence of M. chelonae in intestinal tract is not rare, bile duct may be
      naturally infected with the organism. A case of cholecystitis and cholangitis
      caused by M. chelonae, which has not been reported previously, was found in the T
      hospital.

PMID- 8523850
TI  - [A tuberculosis epidemic in one hospital].
AB  - A Tuberculosis epidemic occurred in a hospital in Fukushima prefecture, 1993. It
      was detected after the diagnosis of two tuberculosis cases among nurses working
      in the hospital. A contact survey in the hospital revealed two another cases of
      tuberculosis, one from the nurse, and the other one from the patient admitted to
      the hospital. In addition, two more nurses in the same hospital were suspected of
      having tuberculosis, but they do not yet started treatment by the time of the
      survey. Though the source of the infection could not be identified, the doctor's
      delay in detecting cases was suspected on the background of the epidemic.
      Deficiency in the health care system of nursing school was also suspected.

PMID- 8523851
TI  - [The present situation, treatment and prognosis of drug-resistant pulmonary
      tuberculosis. Cooperative Study Unit of Chemotherapy of Tuberculosis of the
      National Sanitoria in Japan].
AB  - We studied 266 patients with drug-resistant pulmonary tuberculosis at national
      sanatoria in Japan. The patients included 218 men (mean age, 58 years) and 48
      women (mean age, 62 years). The levels of isoniazid and rifampicin resistance
      were determined at 1 mcg/mL and 50 mcg/mL, respectively. The results were as
      follows. (1) Most patients with drug-resistant pulmonary tuberculosis were middle
      aged or past middle-aged. (2) There were many cases of drug-resistant pulmonary
      tuberculosis in previously treated tuberculosis patients with active disease and
      several cases in previously untreated pulmonary tuberculosis patients. However,
      in some previously untreated patients active tuberculosis was convert relatively
      easily to inactive tuberculosis. (3) Concerning life style, bachelors who drank
      heavily were more likely to develop drug-resistant pulmonary tuberculosis. (4)
      Most cases of drug-resistant pulmonary tuberculosis had at least one cavity on
      chest radiographs. (5) Several patients with drug-resistant tuberculosis left the
      hospital against the advice of their attending doctors; therefore, it was
      difficult to treat their illnesses. (6) In more than half the cases in which
      Mycobacterium tuberculosis was resistant to isoniazid and rifampicin, tolerance
      to streptomycin and ethanbutol was also seen. (7) When patients with drug
      resistant pulmonary tuberculosis continued to have tuberculous bacilli in their
      sputum after 3 months of chemotherapy, there was a tendency for them to
      expectorate tuberculous bacilli in their sputum. For these drug-resistant
      tuberculosis patients, we must pay attention not only to the medical aspects but
      also to the social aspects of their disease.

PMID- 8523852
TI  - [A case of laryngeal and tracheobronchial tuberculosis].
AB  - The patient was 38-year-old male. His chief complaint was persistent cough. He
      had been diagnosed at an another clinic as tuberculosis by positive sputum
      culture. Laboratory findings at the first examination were as follows: ESR was 10
      mm/1 hr and CRP was 0.920 mg/dl and other data were within normal limits. Chest X
      ray showed infiltrative shadow in the left lower lobe. Bronchoscopic findings
      before treatment were as follows: there were ulcers on bilateral vocal cords,
      small white nodules with reddness in trachea and red nodules and white coated
      ulcers in left main bronchus. He was treated with combination chemotherapy (INH,
      RFP, EB) and the steroid inhalation was added 1 month later after the initiation
      of chemotherapy. Bronchoscopic findings at 2 months after starting chemotherapy
      were as follows: lesions of vocal cords and trachea were improved and lesion of
      left main bronchus was scarred without stenosis. Bronchial stenosis as sequelae
      of endobronchial tuberculosis deteriorates the patients' quality of life.
      Therefore it is important to diagnose endobronchial tuberculosis early and to
      start treat with chemotherapy as soon as possible, and the follow up by
      bronchoscopy should be done during treatment.

PMID- 8523853
TI  - [Some problems concerning local cellular immunity in tuberculosis].
AB  - Tuberculous pleurisy is restricted to the pleural cavity and profuse pleural
      fluid, which contains numerous immunocompetent cells, is easily obtained.
      Therefore, tuberculous pleurisy is a good model for the study of local cellular
      immunity. The characteristics and function of lymphocytes in both pleural exudate
      and peripheral blood were studied. The pleural fluid had more T-lymphocytes than
      the peripheral blood. To evaluate predominant T-lymphocyte function in
      tuberculous pleural exudate, we studied the reactions of the lymphocytes to the
      specific antigen. When lymphocytes in pleural effusion were cocultured with
      purified protein derivative (PPD), they reacted to PPD and produced far more
      interferon-gamma (IFN-gamma) than did peripheral blood lymphocytes. Thus,
      exudative-sensitized lymphocytes in morbid sites reacted to the specific antigen
      more strongly. These observations indicate the presence of local cellular
      immunity in tuberculous pleurisy at the morbid site. It would be very interesting
      to know which T-cell subset produces IFN-gamma. When pleural fluid T lymphocytes
      were treated with OKT4 monoclonal antibody and complement, a significant decrease
      in IFN-gamma production was observed in all patients examined, whereas no
      definite decrease in IFN-gamma production was found after treatment with OKT8
      monoclonal antibody and complement. These results suggest that at least the
      OKT4+/OKT8- T-cell subset is responsible for the antigen-specific IFN-gamma
      production in pleural fluid T lymphocytes. With the cooperation of macrophages or
      monocytes, pleural fluid T lymphocytes produced a significant level of
      interleukin 2 (IL-2) in the presence of PPD. Tuberculosis pleural fluid
      macrophages promoted greater IL-2 production than blood monocytes from either
      tuberculosis pleural fluid or blood T lymphocytes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523854
TI  - [The application of molecular biology to the diagnosis of mycobacteriosis].
AB  - The application of molecular biology techniques to the diagnosis of
      mycobacteriosis was evaluated. The hybridization protection assay (HPA) was found
      to be accurate and rapid in the identification of mycobacteria. The nested
      polymerase chain reaction (PCR) targeting the Pab gene was specific and sensitive
      enough for the rapid detection of Mycobacterium tuberculosis in clinical
      specimens. The overall sensitivity and specificity of the nested PCR were
      excellent, 97% and 92%, respectively. In addition, a novel method combining the
      PCR and the HPA for the rapid detection of MAC and M. tuberculosis was developed.
      This method was as useful as the nested PCR for M. tuberculosis above mentioned.
      The clinical usefulness of two commercially available mycobacteria detection
      kits, the MTD and the Amplicor, was evaluated and compared with that of the
      conventional smear and culture methods. The MTD showed the highest sensitivity,
      while the Amplicor showed the highest specificity. The HPA was also applied to
      drug susceptibility tests, which require 3 to 4 weeks by conventional methods. By
      this method, the results of resistance to isoniazid or rifampicin could be
      obtained after three days incubation. Another method for determining the drug
      resistance of mycobacteria is the detection of gene alterations related to the
      drug resistance. The deletion of the catalase-peroxidase gene related to
      isoniazid resistance was observed in 15% of isoniazid-resistant strains. On the
      other hand, point mutations in the RNA polymerase beta subunit (rpoB) gene
      relating to rifampicin resistance were detected in 31% of rifampicin-resistant
      strains by the non-radioisotope PCR-SSCP analysis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8523855
TI  - [Studies on mucociliary transport in patients with pulmonary atypical
      mycobacteriosis--by aerosol inhalation cine-scintigraphy].
AB  - Mucociliary transport (MCT) was studied in 22 patients with atypical
      mycobacteriosis (Group I : 16 with M. avium-intracellulare complex (MAC), Group
      II : 6 with M. kansasii) by aerosol inhalation cine-scintigraphy. In most of the
      patients, the MCT was abnormally slow both in the main bronchus and in the
      trachea, while in healthy controls the transport of the inhaled aerosol in the
      bronchus and the trachea were rapid and smooth. In both groups, the tracheal MCT
      was impaired in two thirds of the patients, while the MCT in the main bronchus
      was impaired in all except one in Group I and in two-thirds in Group II. The
      results indicate that the grade of bronchial impairment was higher in MAC than in
      M. kansasii infections. In atypical mycobacteriosis, especially in MAC
      infections, such impairment of MCT could be closely related to the disruption of
      local defence mechanisms in the airways.

PMID- 8523856
TI  - [Management of nontuberculous mycobacteriosis in health centers and tuberculosis
      surveillance system].
AB  - Nontuberculous Mycobacteriosis (NTM) is a different disease from tuberculosis,
      but in Japan most of them are still obliged to be treated as tuberculosis under
      medical insurance scheme and included statistically in the number of
      tuberculosis. In this investigation, patients of NTM who were at first registered
      as tuberculosis and diagnosed later as NTM or found to be positive for
      nontuberculous mycobacteria were analysed from the standpoint of tuberculosis
      statistics and activities at health centers. Out of 1207 newly registered
      tuberculosis in 1993 at 23 health centers (HCs) or its branches in Hiroshima
      Prefecture, 482 cases were bacteriologically positive, and among them 40 cases
      were found to be NTM later. Under the current tuberculosis surveillance system, 4
      cases from 1 HC were omitted from the tuberculosis registry, 10 cases from 4 HCs
      were kept on the tuberculosis registry as 'culture positive for nontuberculous
      mycobacterium', 15 cases from 7 HCs were registered as 'tuberculosis with
      nontuberculous mycobacteriosis as a complication' and in 11 cases no informations
      on NTM were entered into the registry. Only 6 smear positive cases which were
      registered as 'culture positive for nontuberculous mycobacteria' were excluded
      from the number of smear positive tuberculosis under the surveillance system. In
      other investigation made by hospitals in the same area on NTM, 59 patients with
      definite NTM were reported in 1993. At least 52 were registered first as
      tuberculosis, thus NTM occupies at least 4.3 percent of all newly reported
      tuberculosis and 10.8 percent of new smear positive cases.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8523857
TI  - [Pulmonary infection due to Mycobacterium szulgai associated with multiple
      bullous disease of the lung].
AB  - A 46-years-old male was admitted to our hospital because of productive cough and
      infiltrates on the chest roentogenogram. The patient had a history of left upper
      bullectomy ten years prior to the admission. The CT scan of the chest on
      admission showed infiltrats with cavitation in the left apex and multiple bullae
      in almost whole lung. Microscopical examination of smears of sputum and
      bronchoalveolar lavage fluid revealed acid-fast bacilli. They were identified as
      Mycobacterium szulgai by DNA-DNA hybridization method. The patient was treated
      with isoniazid, streptomycin and rifampicin. After treatment for about a month,
      the culture of sputum converted to negative for M. szulgai. After about three
      months hospitalization, the infiltrates decreased and the cavity wall became
      thin, and no recurrence sign has been observed after the discharge. There are a
      few case reports of pulmonary infection due to M. szulgai associated with bullous
      disease of the lung in Japan.

PMID- 8523858
TI  - [A case of inflammatory bronchial polyp under treatment of tuberculosis].
AB  - A 76-year-old man was admitted to our hospital because of pulmonary tuberculosis.
      He was treated by antituberculosis drugs. Four months later, bronchoscopic
      examination revealed three polypoid tumors. One of them was a small polypoid
      lesion with the pus containing acid-fast bacilli. The others were smooth surfaced
      black polypoid tumors without pus. Although biopsy specimens from these tumors
      showed a non-specific inflammatory change, the former could be considered as a
      tuberculous change. Four months later, the polypoid tumors disappeared and
      anthracosis was found at the site of black polypoid tumors. It is suggested that
      a polypoid tumor with tuberculous findings was in the earlier stage than the
      other tumors during the healing process of bronchial tuberculosis.

PMID- 8523859
TI  - [Trend of tuberculosis among young people observed from data of nationwide
      surveillance system].
AB  - In order to know the trend of TB incidence among people younger than 30 years of
      age, and to clarify the problem of TB control among them, the author used the
      surveillance data, the vital statistics, the annual reports of health center
      activities and others for the past 20 years. While the stagnation of the decline
      of TB incidence rate has been observed since early 1980s, the speed of decline
      among young people has been greater than that among people older than 30 years.
      However, at the same time it is worth attention that the incidence rate of the
      20s is higher than that of those aged 30-39 years, and the slowing off more
      remarkable, during the last several years. It was shown that the recent increase
      of young immigrants from high prevalence countries is affecting the incidence of
      young age group (age 20-29) in Tokyo and the surrounding prefectures with higher
      proportion of these immigrant population. On the other hand, the high incidence
      in the young people observed in Osaka and the surrounding prefectures may be
      attributed to some other social risks. The BCG coverage for children aged 0-4
      years has been increasing and reached to 90% in 1991. The tuberculin test results
      of children in an area seems to reflect the technical level of the testing and
      the age of children to be tested, rather than the TB prevalence of the area. The
      frequency of the young people under chemoprophylaxis is widely variable among
      prefectures. There is poor correlation between this frequency of chemoprophylaxis
      of prefectures and the incidence rate of sputum positive TB, which may be caused
      by disparity in recognition of the necessity of the chemoprophylaxis and the lack
      of efforts for the quality control of the services, such as tuberculin testing.

PMID- 8523860
TI  - [The problems of the young tuberculosis patients in the community tuberculosis
      control].
AB  - In Japan the incidence of tuberculosis has decreased, but recently the decreasing
      speed is slowed down. In young people, the phenomenon is remarkable in the
      incidence for those aged 15-30 years. It will be useful to improve examinations
      of tuberculosis contacts, in order to prevent spread of tuberculosis infection
      among young people. This may also help effectively to identify high-risk groups
      for tuberculosis. Aichi Prefecture has a unique programme that the prefectural
      government can monitor and support the measures taken by the public health
      centers, such as examination of tuberculosis contacts. During last three years
      from 1991 through 1993, 333 tuberculosis cases were reported through this system.
      Of them 143 cases that were younger than 30 years have been analyzed; 65 cases
      were males and 78 were females. Those aged 20-29 years occupied 58% of the cases.
      More than half of the cases were diagnosed by visiting doctors. High school and
      college students occupied 38% of the cases, and nurses, public health nurses, and
      nursery school teachers occupied 20%. Cases whose source of infection was known
      occupied less than 30%, but more than half of them had the sources of infection
      in their families. This programme is very useful for prefectural government to
      get the information how the public health centers implement their measures
      against tuberculosis and to control them.

PMID- 8523861
TI  - [Recent epidemiologic and clinical aspects of adolescent tuberculosis in
      workers].
AB  - The epidemiologic and clinical aspects of tuberculosis have been investigated on
      the young tuberculosis patients (less the 29 years old), utilizing the individual
      records of the periodic health examination in the JR railway workers. The results
      were as follows: 1) Following the gradual decline, the incidence rate of
      tuberculosis in working ages has remained at almost a constant level during last
      ten years. 2) The incidence rate of tuberculosis among young adults has been
      lower than that in elder adults (aged 30 years or older). 3) All young
      tuberculosis patients were detected by the periodic health examination. 4) The
      lower value of body mass index (BMI) was considered as a high risk factor
      associated with development of tuberculosis among young adults, as revealed by a
      case-control study. A case of an outbreak of tuberculosis in a office involving
      10 young cases was presented. It is urgently needed to conduct the contact
      examination eagerly among young workers in order to prevent tuberculosis
      epidemic.

PMID- 8523862
TI  - [Epidemiology of Mycobacterium tuberculosis infection based on RFLP analysis].
AB  - In Japan, the decline of the tuberculosis incidence rates has been slowed down
      since 1970s. To study factors influencing this slow down of the decline, we have
      carried out the analysis of RFLP patterns of 941 strains of M. tuberculosis which
      were isolated at 38 hospitals in various districts of Japan in 1992. The outline
      of the results is as follows; (1) Distribution of the number of IS6110: The
      number of the occurring IS elements varies from 1 to 19, and the majority of the
      isolates have 9 to 14 copies. This finding is identical to the result of the
      previous investigation carried out in 1987 using 123 strains of M. tuberculosis.
      There were groups of individuals with identical patterns among those having the
      same number of copies. The characteristics of the RFLP pattern variety in Japan
      looks like that of Africa where tuberculosis in highly prevalent. In our country,
      however, it is considered that the influence of elderly people is very important.
      Thirty-seven strains contained only one hybridizing band. In 35 of these strains
      the copy was observed in a 7.9 kbp fragment, and in the other two strains the
      copy was observed in a 1.5 kbp fragment. Isolates which contain only one or small
      number of copies could not be differentiated by IS6110, so that other targets for
      RFLP analysis such as IS1081, DR sequence, and PGRS are to be further
      investigated. (2) Cluster analysis was shown to be an appropriate epidemiological
      methodology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8523863
TI  - [Assessment of effectiveness of BCG vaccination against childhood tuberculosis].
AB  - We performed a retrospective analysis of the history of BCG vaccination of 367
      childhood patients who were treated for active tuberculosis (TB) in our hospital
      from 1976 to 1994. Fifty-eight percent of 367 cases, 83.1% of cases under 5 years
      of age and 92% of tuberculous meningitis had not received BCG. To investigate the
      effectiveness of BCG vaccination against TB, we carried out case-control studies
      using 59 patients with TB and 118 controls without TB. The cases were patients
      treated for TB in our hospital from 1988 through Nov. 1994. Two controls were
      chosen for every case with matching for sex, age at admission, year of admission
      and place of residence. Based on whole 59 pairs, BCG vaccination was shown to
      have protective efficacy of 78% (95% confidence interval [CI], 57-89%). For 34
      pairs of under 5 years of age, estimated efficacy was 92% (95%CI, 80-97%), for
      primary pulmonary disease (27 pairs) it was 92% (95%CI, 78-97%). For
      bacteriologically confirmed TB (27 pairs), it was 84% (95%CI, 58-94%), while for
      bacterilogically negative TB (32 pairs) 71% (95%CI, 27-89%). Our results indicate
      that BCG vaccination with multipuncture methold protected considerably against TB
      in infants including primary pulmonary TB.

PMID- 8523864
TI  - [Surveillance of tuberculosis in Japan].

PMID- 8523865
TI  - The Journal of Thoracic and Cardiovascular Surgery Scientific Achievement Award.
      Recipient of 1995 Achievement Award.

PMID- 8523866
TI  - Reduction of monocyte adhesion to xenogenic tissue by endothelialization: an
      adhesion molecule and time-dependent mechanism.
AB  - Great interest has been shown for the seeding of autologous endothelial cells on
      prosthetic materials. We investigated the inflammatory and immunogenic properties
      of xenogeneic tissue before and after seeding with cultured human great saphenous
      vein endothelial cells in vitro. Adhesion of monocytes to xenogeneic tissue with
      or without endothelium and the endothelial cell expression of E-selectin,
      intercellular adhesion molecule 1, vascular adhesion molecule 1, and major
      histocompatibility complex class II antigens were investigated 1, 3, and 7 days
      after seeding. Both monocyte adhesion and endothelial adhesion molecule
      expression were relatively high 1 day after seeding and were significantly
      lowered after 3 to 7 days. There was no difference between monocyte adhesion and
      adhesion molecule expression on viable or nonviable xenogeneic tissue. Monocyte
      adhesion and adhesion molecule expression increased after interleukin-1 beta or
      interferon-gamma stimulation of the endothelial cells. The results suggest that
      human endothelial cells exhibit an early proinflammatory and immunogenic activity
      immediately after seeding. Three and 7 days after seeding, the endothelialized
      surface is less adhesive for monocytes as compared with nonendothelialized
      tissue. These findings have implications when cultured or intraoperatively
      recruited endothelial cells are used clinically.

PMID- 8523867
TI  - A technique to simplify and improve exposure in heart-lung transplantation.
AB  - Heart-lung transplantation is associated with high perioperative mortality rates.
      A modified operative technique was used by one surgeon operating on 17 patients
      at the University of Arizona, Tucson, and the Inland Northwest Thoracic Organ
      Transplant Program, Spokane, Washington. This technique gives greater exposure to
      the area of dissection behind the heart-lung block after implantation and makes
      maintaining hemostasis easier. No deaths from bleeding complications occurred and
      no reoperations for bleeding were required with this technique. The Kaplan-Meier
      survival was 82% at 1 year. This technique simplifies a difficult technical
      procedure and may reduce mortality rate.

PMID- 8523868
TI  - Confirmation of the safety of autologous blood donation by patients awaiting
      heart or lung transplantation. A controlled study using hemodynamic monitoring.
AB  - BACKGROUND: Though earlier investigations have demonstrated the efficacy of
      autologous blood transfusion in reducing allogeneic blood exposure in patients
      undergoing heart or lung transplantation, questions remain regarding the safety
      of blood donation by patients with severe heart or lung disease. METHODS:
      Response to autologous blood donation by candidates for heart and lung
      transplantation and a group of age- and gender-matched control subjects was
      studied. Heart rate, blood pressure, oxygen saturation, and cardiac rhythm were
      examined before and after phlebotomy, and response to orthostatic challenge was
      evaluated. Patients were also questioned regarding impressions of changes in
      subjective sense of well being. Differences between patients and control subjects
      were evaluated by the paired t test and Fisher's exact test. An alpha of 0.05 was
      used in all testing to determine statistical significance. RESULTS: Eighteen
      candidates for heart transplantation, 16 candidates for lung transplantation, and
      their matched control subjects were studied. Though patients and control subjects
      differed with respect to baseline hemodynamic measurements, significant
      differences between the groups' responses to phlebotomy were not observed. After
      whole blood donation, orthostatic challenge resulted in a mean change in mean
      arterial pressure of -2.1 mm Hg in candidates for heart transplantation compared
      with a mean of +3.6 mm Hg in their control subjects (p = 0.062). In candidates
      for lung transplantation there was a mean change of +2.2 mm Hg after orthostatic
      challenge versus a mean change of +8.5 mm Hg in their control subjects (p =
      0.052). Furthermore, no changes in cardiac rhythm or arterial oxygen saturation
      were detected. CONCLUSIONS: The hemodynamic effects of autologous blood donation
      in a group of patients with significant cardiac or pulmonary disease were not
      different from those observed in patients considered acceptable candidates for
      autologous blood collection. On the basis of these objective findings, we believe
      that patients with less severe degrees of heart or lung disease should not be
      excluded from participation in autologous blood donation programs.

PMID- 8523869
TI  - Atrial natriuretic peptide release at rest and with exercise after cardiac
      transplantation with bicaval anastomoses.
AB  - Bicaval anastomoses in orthotopic cardiac transplantation offer the advantage of
      preserving the right atrial geometry. To elucidate the impact of this anastomotic
      technique on atrial natriuretic peptide plasma levels at rest and with exercise,
      nine patients were submitted to a symptom-limited supine exercise test. Atrial
      natriuretic peptide plasma levels in samples obtained from the right atrium were
      elevated at rest (274.4 +/- 60.4 pg/ml), at peak exercise (438.1 +/- 71.7 pg/ml),
      and thereafter (328.1 +/- 71.2 pg/ml) with respect to normal reference values of
      21 +/- 1 pg/ml at rest and 92 +/- 14 at peak exercise. Renin, angiotensin, and
      aldosterone plasma levels were almost normal and did not indicate any pathologic
      processes in volume homeoostasis. Right-sided hemodynamic parameters were not
      correlated with atrial natriuretic peptide secretion. An adverse relationship
      between cold ischemic time of the donor organ and atrial natriuretic peptide
      release was found (r = 0.88, p < 0.0008), indicating that endocrine cardiocytes
      are sensitive to prolonged ischemia. Atrial natriuretic peptide release may thus
      be independent of the surgical approach, and other unique characteristics of the
      transplanted heart, such as denervation, are more likely to be responsible for
      elevated atrial natriuretic peptide plasma concentrations after orthotopic heart
      transplantation.

PMID- 8523870
TI  - Preconditioning with potassium channel openers. A new concept for enhancing
      cardioplegic protection?
AB  - Ischemic preconditioning defines an adaptive endogenous mechanism in which a
      brief episode of reversible ischemia renders the heart more resistant to a
      subsequent period of sustained ischemia. Because the cardioprotective effects of
      ischemic preconditioning might be mediated by an activation of adenosine
      triphosphate-sensitive potassium channels, this study was designed to assess
      whether these effects could be duplicated by the preischemic administration of a
      potassium channel opener. Fifty isolated isovolumic buffer-perfused rat hearts
      underwent 45 minutes of normothermic potassium arrest followed by 1 hour of
      reperfusion. They were divided into five equal groups that differed with regard
      to the preconditioning regimen: Group 1 hearts were left untreated and served a
      controls; in group 2, preconditioning was achieved with 5 minutes of total global
      ischemia followed by 5 minutes of buffer reperfusion before cardioplegic arrest;
      in group 3, the preconditioning stimulus consisted of a 5-minute infusion of the
      potassium channel opener nicorandil (10 mumol/L) followed by 5 minutes of drug
      free buffer perfusion before arrest; group 4 hearts underwent a similar protocol
      except that the infusion of nicorandil was preceded by that of the potassium
      channel blocker glibenclamide (10 mumol/L); group 5 hearts were ischemically
      preconditioned like those of group 2 except that the no-flow preconditioning
      period was also preceded by a 5-minute infusion of glibenclamide (50 mumol/L).
      The results demonstrate that ischemic preconditioning significantly improved
      contractility and reduced contracture during reperfusion, as compared with
      results in control hearts. These protective effects were duplicated by
      pretreatment with nicorandil but were abolished when the drug was antagonized by
      a prior infusion of glibenclamide. Likewise, the glibenclamide-induced blockade
      of potassium channels largely blunted the beneficial effects of ischemic
      preconditioning. These data suggest that opening of adenosine triphosphate
      sensitive potassium channels substantially contributes to preconditioning-induced
      cardiac protection in a surgically relevant model of global ischemia and,
      consequently, that the use of potassium channel openers like nicorandil could be
      an effective means of enhancing cardioplegic protection.

PMID- 8523871
TI  - Safety and efficacy of aprotinin under conditions of deep hypothermia and
      circulatory arrest.
AB  - Aprotinin has been successfully used to reduce blood loss and blood product
      requirements in patients undergoing primary and reoperative cardiac operations.
      Its safety and efficacy during profound hypothermia and circulatory arrest have
      been questioned, however. A retrospective review compared 24 patients who
      received aprotinin during complex aortic procedures under profound hypothermia
      and circulatory arrest with 24 age-matched patients undergoing similar procedures
      without aprotinin. Activated clotting time was maintained at longer than 500
      seconds (kaolin activating agent) or longer than 750 seconds (celite). We
      observed no statistically significant difference in the incidence of neurologic
      events (p not significant) or myocardial infarctions (p not significant), and
      there was a trend toward reduced in-hospital mortality rate in aprotinin-treated
      patients. A higher incidence of postoperative renal dysfunction was encountered
      in aprotinin-treated patients. Aprotinin recipients had a significant reduction
      in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude
      that aprotinin may be safely and effectively used in patients undergoing deep
      hypothermia and circulatory arrest.

PMID- 8523872
TI  - Complement and granulocyte activation in two different types of heparinized
      extracorporeal circuits.
AB  - Complement and granulocyte activation were studied in cardiopulmonary bypass
      circuits completely coated with either end-attached covalent-bonded heparin, the
      Carmeda BioActive Surface, or with the Duraflo II bonded heparin, in combination
      with reduced systemic heparinization (activated clotting time > 250 seconds). The
      control groups were perfused with uncoated circuits and full heparin dose
      (activated clotting time > 480 seconds). Altogether 67 patients undergoing
      elective first-time myocardial revascularization were investigated, having
      extracorporeal perfusion with a Duraflo II coated circuit (n = 17), an identical
      but uncoated circuit (n = 17), a Carmeda coated circuit (n = 17), or an
      equivalent uncoated circuit (n = 16). During cardiopulmonary bypass, the C3
      activation products C3b, iC3b, and C3c (C3bc) and the terminal SC5b-9
      complemented complex increased markedly in all four groups compared with
      baseline, but significantly less in the two coated groups than in their control
      groups. Additionally, a significantly lower concentration of C3bc was observed in
      the Carmeda coated group, with maximal increase of median 28 AU/ml compared with
      50 AU/ml in the Duraflo II coated group (p = 0.003). Similarly, in the Carmeda
      coated group, the maximal increase of terminal complement complex was
      considerably lower (0.8 AU/ml) than the levels recognized in the Duraflo II
      coated group (2.4 AU/ml) (p < 0.001). The release of the granulocyte activation
      myeloperoxidase and lactoferrin increased from the beginning of the operation,
      with peak levels at the end of bypass. A significant reduction of lactoferrin
      release was recognized when comparing the coated groups with the control groups.
      The difference between the two coated groups (Carmeda 228 micrograms/L; Duraflo
      II 332 micrograms/L; p = 0.05) was marginally significant. For myeloperoxidase,
      no significant differences were observed between the coated and uncoated groups.
      In conclusion, both types of heparin-coated circuits reduced complement
      activation and release of lactoferrin, but the Carmeda circuit proved to be more
      effective than the Duraflo II equipment.

PMID- 8523873
TI  - Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic
      inflammatory response in patients having coronary bypass.
AB  - Cardiopulmonary bypass generates a systemic inflammatory response, including the
      activation of leukocytes, contributing to postoperative morbidity. To evaluate
      whether the use of heparin-treated extracorporeal circuits could reduce the
      inflammatory reaction in patients undergoing cardiopulmonary bypass, we conducted
      a prospective clinical study on 14 patients having coronary artery bypass in whom
      perfusion was done randomly with either Duraflo II heparin-treated circuits or
      with nontreated circuits. In both groups systemic heparinization was performed
      before cardiopulmonary bypass. The use of heparin-treated circuits resulted in a
      reduction of systemic inflammatory activation during cardiopulmonary bypass. This
      was reflected by lower plasma levels of soluble tumor necrosis factor receptors
      (p < 0.05) and of interleukin-6 and interleukin-8 (p < 0.05), manifest after
      release of the aortic crossclamp. Furthermore, 6 and 12 hours after aortic
      crossclamp release significantly lower levels of the soluble E-selectin (p <
      0.05) were observed in the Duraflo II group. In patients in whom noncoated
      circuits were used, a significant decrease in circulating soluble intercellular
      adhesion molecule 1 (p < 0.05) was found early during bypass. All these
      observations suggest that the use of a heparin-treated extracorporeal circuit
      reduces the systemic inflammatory activation and may after the leukocyte
      endothelium interaction.

PMID- 8523874
TI  - Zinc supplementation enhances the effectiveness of St. Thomas' Hospital No. 2
      cardioplegic solution in an in vitro model of hypothermic cardiac arrest.
AB  - The present study was done to assess the effectiveness of a zinc-supplemented
      cardioplegic solution in an in vitro model of hypothermic arrest. Isolated hearts
      were perfused in the nonworking mode. All hearts were subjected to 2 hours of
      hypothermic arrest, at 10 degrees C, followed by 60 minutes of recovery. In
      protocol 1, arrest was initiated with infusion of cardioplegic solution with or
      without 30 mumol/l zinc for 5 minutes, which was then reinfused for 5 minutes
      every 15 minutes during arrest. In protocol 2, arrest was initiated with infusion
      of cardioplegic solution with or without 40 mumol/L zinc for 10 minutes.
      Cardioplegic solution (without zinc) was then reinfused for 5 minutes before the
      hearts were rewarmed. In protocol 1 hearts, peak postischemic left ventricular
      developed systolic pressure was 106 +/- 5 mm Hg and 80 +/- 3 mm Hg in zinc
      treated versus control hearts, respectively (p < 0.05 by repeated-measures
      analysis of variance). In protocol 2 hearts, recovery of postischemic left
      ventricular developed systolic pressure peaked at 74 +/- 4 mm Hg and 46 +/- 8 mm
      Hg in zinc-treated and control hearts, respectively (p 0.05, repeated-measures
      analysis of variance). Similar effects were observed for the left ventricular
      rate of relaxation (p < 0.05, repeated-measures analysis of variance). Except for
      some minor effects, lactate dehydrogenase release was not affected by zinc
      supplementation. The present study demonstrates that zinc supplementation further
      enhances the normally observed preservation of postarrest cardiac function and
      suggests possible clinical utility for this metal as an additive to standard
      crystalloid cardioplegic solutions.

PMID- 8523875
TI  - Blood gas management and degree of cooling: effects on cerebral metabolism before
      and after circulatory arrest.
AB  - This study investigated the effects of different cooling strategies on cerebral
      metabolic response to circulatory arrest. In particular, it examined the impact
      of blood gas management and degree of cooling on cerebral metabolism before and
      after deep hypothermic circulatory arrest. Sixty-nine 1-week-old piglets (2 to 3
      kg) were placed on cardiopulmonary bypass (37 degrees C) at 100 ml/kg per minute.
      Animals were cooled to 18 degrees or 14 degrees C as follows: alpha-stat strategy
      to 18 degrees C (n = 9) or 14 degrees C (n = 6), pH-stat strategy to 18 degrees C
      (n = 12) or 14 degrees C (n = 10). Animals underwent 60 minutes of circulator
      arrest followed by rewarming with alpha-stat strategy to 36 degrees C. Control
      animals were cooled with alpha-stat strategy to 18 degrees C (n = 10) or 14
      degrees C (n = 3) and then maintained on cold cardiopulmonary bypass (100 ml/kg
      per minute) for 60 minutes. Three animals were excluded (see text). With the use
      of xenon 133 clearance methods, cerebral blood flow was measured at the following
      points: point I, cardiopulmonary bypass (37 degrees C); point II, cardiopulmonary
      bypass before circulatory arrest or control flow (18 degrees or 14 degrees C);
      and point III, cardiopulmonary bypass after rewarming (36 degrees C). Cerebral
      metabolic rate of oxygen consumption was calculated for each point. At point II,
      cerebral metabolism was more suppressed at 14 degrees C compared with that at 18
      degrees C. At any given temperature (18 degrees or 14 degrees C), pH-stat
      strategy provided the greatest suppression of of cerebral metabolism. In control
      animals, cerebral metabolic oxygen consumption of point III returned to baseline
      values after 60 minutes of cold bypass. Sixty minutes of circulatory arrest
      resulted in a significant reduction in cerebral metabolic oxygen consumption at
      point III compared with that at point I regardless of cooling temperature or
      blood gas strategy. The amount of cerebral metabolic recovery was significantly
      reduced in the pH-stat 14 degrees C group compared with that in the pH-stat 18
      degrees C group at point III. The use of pH-stat strategy followed by a switch to
      alpha-stat at 14 degrees C provided better cerebral metabolic recovery compared
      with either strategy used alone. The use of pH-stat strategy during initial
      cooling may provide the animal with maximal cerebral metabolic suppression. The
      cerebral acidosis produced with pH-stat cooling may worsen cerebral metabolic
      injury from circulatory arrest, but this affect is eliminated with the use of
      alpha-stat just before the period of circulatory arrest.

PMID- 8523876
TI  - Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced
      inflammation in humans.
AB  - Cardiopulmonary bypass induces an inflammatory state characterized by tumor
      necrosis factor-alpha release. Integrin CD11b is a neutrophil surface adhesive
      glycoprotein integrin that is rapidly and permanently unregulated by tumor
      necrosis factor-alpha exposure. The CD11b integrin is known to be the primary
      neutrophil integrin responsible for neutrophil lung and myocardial entrapment
      after cardiopulmonary bypass and subsequent reperfusion injury. Twenty-four
      adults admitted to the hospital for myocardial revascularization were equally
      randomized to one of three groups: group A (control), group B (methylprednisolone
      before cardiopulmonary bypass), and group C (low-dose aprotinin protocol). Blood
      was collected at three times: (1) baseline, (2) 50 minutes of cardiopulmonary
      bypass duration, and (3) 30 minutes after cardiopulmonary bypass termination.
      Neutrophil CD11b integrin expression was measured by fluorescence-activated cell
      sorter analysis and plasma tumor necrosis factor-alpha levels measured by enzyme
      linked immunosorbent assay. Group A demonstrated significant (p < 0.05) increases
      in CD11b expression at times 2 and 3 when results were compared with those of the
      same group baseline and with those of groups B and C at similar times. No
      significant changes were noted between groups B and C at any time. Group A
      demonstrated a significant (p < 0.05) increase in levels of tumor necrosis factor
      alpha at time 3 when results were compared with those of the same group baseline
      and of groups B and C at the same time. No significant changes were noted between
      B and C at any time. These results demonstrate low-dose aprotinin has a similar
      antiinflammatory effect to that of methylprednisolone in blunting cardiopulmonary
      bypass-induced systemic tumor necrosis factor-alpha release and neutrophil
      integrin CD11b upregulation.

PMID- 8523877
TI  - Myocardial performance in elderly patients after cardiopulmonary bypass is
      suppressed by tumor necrosis factor.
AB  - The aim of this study was to determine whether elderly patients (aged > or = 65
      years, n = 20) in comparison with younger patients (aged < or = 55 years, n = 23)
      demonstrate a different biochemical and hemodynamic response to coronary artery
      bypass operations. In the elderly group, we calculated a smaller body surface
      area (p < 0.01) than that in the younger group, and more female patients were
      included in this group (p < 0.05). During cardiopulmonary bypass, the elderly had
      higher endotoxin plasma concentrations (p < 0.01) than the younger patients, and
      significantly more circulating tumor necrosis factor-alpha was found after
      operation (p < 0.04). In the intensive care unit, the elderly patients had a
      significantly higher pulmonary capillary wedge pressure (p < 0.001), a higher
      mean pulmonary artery pressure (p < 0.01), and a lower calculated left
      ventricular stroke work index (p < 0.05). Multivariate analysis for the
      postoperative outcome showed that the intergroup differences in tumor necrosis
      factor-alpha, mean pulmonary artery pressure, and pulmonary capillary wedge
      pressure could be explained mainly by the difference in age between the groups
      and that the calculated left ventricular stroke work index difference could be
      explained by the difference in circulating tumor necrosis factor-alpha levels.
      Thus in elderly patients higher circulating endotoxin and tumor necrosis factor
      alpha concentrations were detected than in younger patients, which clinically
      resulted in a suppressed myocardial performance.

PMID- 8523878
TI  - Differential diagnosis of thymic carcinoma and lung carcinoma with the use of
      antibodies to cytokeratins.
AB  - There are few specific pathologic findings that can be relied on to distinguish
      primary thymic carcinomas from lung carcinomas with mediastinal extension or
      showing metastasis to the anterior mediastinum. The immunohistochemical
      reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are
      histologically similar to each other, was examined with the use of monoclonal
      antibodies to cytokeratins 7 and 13. Among keratinizing squamous cell carcinomas,
      all thymic carcinomas reacted with antibody specific for cytokeratin 7 (9/9, 0%),
      whereas no staining reaction was seen in lung carcinomas (0/5, 0%) (p < 0.01).
      This finding can be used as a diagnostic aid in primary thymic keratinizing
      squamous cell carcinomas to expedite treatment and prognosis. Cytokeratin 7 and
      cytokeratin 13 monoclonal antibodies reacted with almost all cases of thymic
      carcinoma. Applications of monoclonal antibodies specific for certain
      cytokeratins, especially 7 and 13, may be helpful in the diagnosis of other
      subtypes of thymic carcinomas.

PMID- 8523879
TI  - Management of flail chest injury: internal fixation versus endotracheal
      intubation and ventilation.
AB  - A total of 427 patients with major chest trauma were treated in two major
      hospitals in Abu Dhabi, United Arab Emirates, during a 10-year period. In 64 of
      426 patients, flail chest injury was the dominant factor among other injuries
      that were insignificant. Among 64 cases of flail chest injury, 25 were managed by
      internal fixation of ribs, whereas the remaining 38 were managed by endotracheal
      intubation and intermittent positive-pressure ventilation alone. Of the patients
      treated by internal fixation 80% (21/26) were weaned from the ventilator within
      an average of 1.3 days, whereas the remaining 20% (5/26) continued to need
      assisted ventilation for a longer duration; the total average duration of
      assisted ventilation for the whole group was 3.9 days. In comparison, among 38
      patients with flail chest injury treated by endotracheal intubation and
      ventilation alone, the average duration of assisted ventilation was 15 days. In
      the group treated by internal fixation 11% (3/26) of the patients ultimately
      required a tracheotomy, whereas in the patients treated by intubation and
      ventilation alone tracheostomy was required in 37% (14/38) of the cases. In the
      group treated by internal fixation, chest infection was documented in 15% (4/26),
      septicemia in 4% (1/26), and barotrauma in 0%; in the other group these
      complications occurred in 50% (19/38), 24% (9/38), and 8% (3/38) of the cases,
      respectively. The mortality rate was 8% (2/26) in the surgically treated
      patients, whereas it was 29% (11/38) in the other group. All the deaths in both
      groups were ascribed to adult respiratory distress syndrome. Average stay in the
      intensive care unit was 9 days for the patients treated by internal fixation,
      whereas it was 21 days in the group treated by intubation and ventilation alone.
      The treatment of flail chest injury in our series by internal fixation resulted
      in speedy recovery, decreased complications, and better ultimate cosmetic and
      functional results and proved to be cost effective.

PMID- 8523880
TI  - Video-assisted thoracoscopic surgical interruption: the technique of choice for
      patent ductus arteriosus. Routine experience in 230 pediatric cases.
AB  - Video-assisted thoracoscopic surgical interruption for patient ductus arteriosus
      is a well-standardized procedure already described. We present our entire series
      of such cases, from the first case (performed on Sept. 5, 1991) to March 1, 1995.
      Two hundred thirty patients in a variety of age groups underwent video-assisted
      interruption: younger than 6 months (70 patients, 30%), 6 to 48 months (123
      patients, 54%), and older than 48 months (37 patients, 16%). The mean weight was
      12.6 kg (range 1.2 to 65 kg). Thirty-nine patients had symptomatic pulmonary
      hypertension. Associated intracardiac anomalies included atrial septal defect
      (three), ventricular septal defect (five), and anomalous pulmonary venous return
      (one). All patients underwent video-assisted interruption of the patient ductus
      arteriosus with two titanium clips. Closure was evaluated by postoperative
      echocardiography before extubation. Five patients had a persistent patent ductus
      after video-assisted interruption, all early in our experience and related to
      insufficient dissection resulting in inadequate clip placement. Four patients had
      successful immediate clip repositioning (three by video-assisted interruption and
      one by thoracotomy). Subsequent echocardiography revealed persistent closure in
      these patients. A persistent patent ductus arteriosus with minimal flow was
      discovered in one patient without symptoms after discharge. Recurrent laryngeal
      nerve dysfunction was noted in six patients (2.6%, five transient and one
      persistent). There were no deaths, hemorrhages, transfusions required, or
      chylothoraces in this series. Mean operative time was 20 +/- 15 minutes, and
      hospital stay averaged 48 hours for patients younger than 6 months and 72 hours
      for patients older than 6 months. This is a safe, rapid, cost-effective technique
      that results in excellent results and a shortened hospital stay. Video-assisted
      interruption represents the technique of choice for closure of a patient ductus
      arteriosus.

PMID- 8523881
TI  - Postbypass effects of delayed rewarming on cerebral blood flow velocities in
      infants after total circulatory arrest.
AB  - Cerebral perfusion is reduced after prolonged periods of total circulatory arrest
      in infants. Methods of rewarming after arrest may modify the flow pattern of
      recovery, and a single report has suggested that using cold reperfusion to delay
      rewarming could mitigate abnormalities in cerebral blood flow. Cerebral perfusion
      was evaluated by transcranial Doppler sonography in 16 infants who required
      periods of total circulatory arrest of 35 minutes or more. In group A (n = 9)
      rewarming was begun immediately on reperfusion, whereas in group B (n = 7) a 10
      minute period of cold reperfusion was instituted before rewarming was begun. The
      mean and end-diastolic flow velocities were measured before incision (baseline)
      and at 20, 45, and 90 minutes after conclusion of cardiopulmonary bypass. Mean
      arterial pressure, hematocrit value, and arterial carbon dioxide tension were
      controlled, with no significant differences between the two groups (p > 0.05). In
      group A, the mean cerebral blood flow velocity was below the baseline level at
      all three postbypass measurements (p < 0.001). In group B, however, mean velocity
      did not differ significantly from the baseline value (p > 0.05). Twenty minutes
      after bypass, 89% of the patients in group A had no diastolic Doppler signal,
      indicating absence of perfusion during diastole, compared with only 28% in group
      B (p = 0.02). These preliminary results suggest that a delay in rewarming on
      reperfusion may be beneficial in infants after circulatory arrest.

PMID- 8523882
TI  - Univentricular repair. Early and midterm results.
AB  - A total of 202 patients (62 with tricuspid atresia and 140 without tricuspid
      atresia) underwent univentricular repair at our unit from January 1990 to
      September 1994. Of these patients, 182 had nonfenestrated and 20 had fenestrated
      interatrial baffles. Early mortality was 15.9% (29/182) in the group with
      nonfenestrated baffles and 5% (1/20) in the group with fenestrated baffles. The
      follow-up period ranged from 2 to 58 months. Seven late deaths occurred, and five
      patients were lost to follow-up. Of 160 patients who have been evaluated in the
      outpatient department in the past 3 months, 142 (88.75%) required no cardiac
      medicines and were in functional class I. Risk factors analyzed for early
      mortality and significant effusion were age, preoperative diagnosis, type of
      Fontan modification, cardiopulmonary bypass time, aortic crossclamp time,
      pulmonary artery size, associated pulmonary arterioplasty, takedown of systemic
      pulmonary artery shunt, and pulmonary artery debanding, along with the Fontan
      operation. Bypass time exceeding 120 minutes was associated with a higher early
      mortality (12/47 vs 18/155; p = 0.0187). Bypass time exceeding 120 minutes (p =
      0.0456) and aortic crossclamp time exceeding 60 minutes (p = 0.0278) were
      associated with significant postoperative effusion. Other factors were not
      associated with any significantly increased risk for early mortality or
      postoperative effusions. Fenestration of the interatrial baffle appeared to
      decrease early mortality, although the numbers are too small to be statistically
      significant. The prevalence of effusions did not differ significantly between the
      group with fenestrated baffles and the group without fenestrated baffles.

PMID- 8523883
TI  - Surgical treatment of patients with Wolff-Parkinson-White syndrome and associated
      Ebstein's anomaly.
AB  - Ebstein"s anomaly is the most common congenital heart disease associated with the
      Wolf-Parkinson-White syndrome. Between November 1973 and March 1993, we
      surgically treated 42 patients with Wolff-Parkinson-White syndrome and Ebstein's
      anomaly. The patient's ages ranged from 5 months to 59 years (mean 35.3 +/- 14.0
      years). There were a total of 52 accessory pathways, 48 of which were located in
      the right (65%) or posteroseptal (29%) area. A left-sided accessory pathway was
      seen in only two patients (3.8%). Division of all right-sided accessory pathways
      was done during normothermic cardiopulmonary bypass with the heart beating;
      cryocoagulation was applied together with scalpel dissection of the
      atrioventricular groove. Division of the left-sided accessory pathways was done
      with the use cold potassium cardioplegic arrest. Thirty-five of these patients
      underwent tricuspid valve operation for Ebstein's anomaly and 11 of them
      underwent tricuspid valve replacement with a bioprosthesis. All 52 accessory
      pathways were successfully divided, although two patients required reoperation
      because of tachycardia caused by accessory pathways in different positions. Three
      hospital deaths (7.1%) occurred. There were no late deaths during the follow-up
      period (mean 94.3 +/- 52.4 months), but two patients required repeat tricuspid
      operation because of progression of the tricuspid regurgitation. Because no
      repeat operations were required during long-term follow-up patients who underwent
      valve repair or valve replacement, correction should be indicated in some
      patients.

PMID- 8523884
TI  - The prevalence of infective endocarditis after aortic valve replacement.
AB  - Replacement valve endocarditis occurred in 3.7% of 2443 patients who underwent
      primary or redo aortic valve replacements at The Prince Charles Hospital between
      December 31, 1969 and January 1, 1992, based on a cross-sectional follow-up in
      1992 which was 98.8% complete. Because some patients had re-replacements during
      the study period, a total of 2686 operations were considered for analysis. A
      variety of replacement devices were used, including 571 allografts (21%), 1152
      xenografts (43%), and 880 mechanical valves (36%). Insertion of an allograft
      valve resulted in a constant risk of endocarditis which, by multivariable hazard
      function analysis, negated the effect of any early-phase factors (p < 0.0001).
      With other replacement devices, the risk of infection peaked early after
      operation (9 weeks) and then gave way to a constant risk. Compared with the risk
      associated with allograft valves, constant risk was higher when the replacement
      device was a Carpentier-Edwards xenograft (n = 1021, p = 0.02) and lower when a
      St. Jude Medical mechanical valve was used (n = 505, p = 0.05). In nonallograft
      recipients, the presence of active preoperative endocarditis (p < 0.0001) or a
      concomitant synthetic synthetic aortic root replacement (p = 0.0006) increased
      the magnitude of the early peaking risk. Regardless of replacement device,
      constant risk was increased in patients with renal dysfunction (p = 0.01), in
      younger patients 0.04). When preoperative endocarditis was caused by
      Staphylococcus aureus, culture-positive postoperative wound infection was
      associated with increased risk of replacement valve infection (p < 0.001) and
      when it occurred, the same organism was usually responsible (86%). Identification
      of patients at increased risk for replacement valve infection may lead to reduced
      morbidity through strategies such as selective use of replacement devices and
      antimicrobial prophylaxis.

PMID- 8523885
TI  - New temporary atrial and ventricular pacing leads for patients after cardiac
      operations.
AB  - We have studied two new temporary pacing leads (Medtronic 6491 and 6492) intended
      for pacing after cardiac operations. The conductor has stainless steel strands
      coated with polyethylene connected to a 4' mm2 surface area, stainless steel,
      smooth, tapered electrode. A soft 4-0 coiled polypropylene fiber served as as
      fixation mechanism in the heart. The study included 15 children (aged 3 months to
      7 years, body weight 4.4 to 20 kg) with a variety of congenital heart defects and
      15 adults (aged 45 to 78 years) with coronary artery disease (n = 13) and aortic
      valve disease (n = 2). A pair of leads each was placed in a bipolar fashion in
      the right atrial wall and nonsystemic ventricle in the children (median implant
      duration 12 days) and in the right atrial wall only in the adults (median implant
      duration 9 days). The atrial current threshold values in children increased from
      0.61 +/- 0.34 mA immediately after implant to 2.08 +/- 1.86 mA at explant (p <
      0.002). In the adults the threshold values increased from 0.95 +/- 1.44 mA
      immediately after implant to 2.76 +/- 2.76 mA at explant (p < 0.002). In the
      ventricle the threshold values increased from 0.38 +/- 0.13 mA immediately after
      implant to 2.22 +/- 1.63 mA at explant (p < 0.002). Tissue resistance immediately
      after implant measured 809 +/- 182 omega at explant (children, p = not
      significant). Corresponding values in adults were 778 +/- 190 omega and 599 +/-
      91 omega (p < 0.004). In the ventricle resistances changed from 1019 +/- 143
      omega to 876 +/- 137 omega (p < 0.05). P wave amplitudes measured 1.8 +/- 1.5 mV
      immediately after implant and decreased to 1.6 +/- 1.2 mV at explant (p = not
      significant, children) and 2.0 +/- 1.3 mV to 1.8 mV (p = not significant,
      adults). R wave amplitude were 13.1 +/- 3.0 mV immediately after implant and fell
      to 8.7 +/- 4.5 mV at explant (p < 0.005). Thus, threshold values, tissue
      resistances, and electrogram and pliable amplitudes assured a safe pacemaker
      function. The small diameter and pliable texture of these leads provided a smooth
      surgical handling. They were found particularly suitable in children.

PMID- 8523886
TI  - Fresh venous allografts in peripheral arterial reconstruction in dogs. Effects of
      histocompatibility and of short-term immunosuppression with cyclosporine A and
      mycophenolate mofetil.
AB  - To date, no arterial substitute has been shown to be as effective as the
      autologous saphenous vein in peripheral revascularization procedures. In the
      present study, the venous allograft was evaluated as a vascular substitute in
      terms of patency and induction of host immune reactivity, whether used in major
      histocompatibility complex-incompatible, major histocompatibility complex
      incompatible dogs. The immunosuppressive drug therapies were given for a period
      of 31 days, beginning 1 day before transplantation, and consisted of the use of
      cyclosporine A, mycophenolate mofetil, or a combination of both. All
      histoincompatible allografts were thrombosed at 4 or 8 weeks after
      transplantation with antibody development and cell-mediated cytotoxicity in the
      graft, whereas histocompatible allografts showed late stenosis without
      immunologic reactions directed toward donor cells. Given alone, neither
      cyclosporine A nor mycophenolate mofetil improved the overall patency of venous
      allografts; thrombosis occurred shortly after cessation of immunosuppression.
      Still, the cyclosporine A-mycophenolate mofetil combination therapy led to a 100%
      patency rate at 20 weeks after implantation and immune reactions were markedly
      reduced. This study shows that the fresh vein allograft is still an attractive
      and functional alternative to the autologous saphenous vein if the host
      immunologic reactions are controlled by cyclosporine A-mycophenolate mofetil
      immunosuppression.

PMID- 8523888
TI  - A comparison of macroscopic lipid content within porcine pulmonary and aortic
      valves. Implications for bioprosthetic valves.
AB  - Lipid droplets have been demonstrated within both explanted porcine bioprostheses
      and normal porcine aortic valves. Because of the increasing interest in pulmonary
      valves as an allograft or xenograft aortic valve substitute, we examined the
      incidence and distribution of such lipid deposits in 50 porcine aortic valves and
      50 matched porcine pulmonary valves. All 300 cusps were removed with surgical
      scissors and, under a dissecting microscope, the ventricularis layer was removed
      to expose the spongiosal layer. Macroscopic extracellular lipid droplets analyzed
      by means of a dissecting microscope with an eyepiece grid and stereology point
      counting techniques to provide an area-density average spatial probability map
      for each cusp. Only 8% of porcine aortic valves were free of lipid, with the
      distribution of the lipids being 52% +/- 14% right coronary cusp, 90% +/- 8% left
      coronary cusp, and 68% +/- 13% noncoronary cusp. Of the pulmonary valves, 60%
      were free of lipid, with the incidence of lipids being 26% +/- 12% left cusp, 6%
      +/- 7% right cusp, and 12% +/- 9% anterior cusp. Subsequently, lipid cluster
      samples underwent thin-layer chromatography, which showed them to be
      phospholipids, oleic acid (fatty acid), triglycerides, and unesterified
      cholesterol. One primary mode of bioprosthetic valve failure is leaflet
      calcification. The similarity of distribution within the spongiosal layer between
      leaflet calcification and intrinsic cusp lipids suggests that the observed lipids
      might act as a nucleation site for calcification. The substantially lower
      incidence of lipid in pulmonary valves therefore may represent a potential
      benefit when these valves are considered for use as aortic valve replacements.

PMID- 8523887
TI  - Surgical management of infective endocarditis associated with cerebral
      complications. Multi-center retrospective study in Japan.
AB  - To establish guidelines for the surgical treatment of patients with infective
      endocarditis who have cerebrovascular complications, we conducted a detailed
      retrospective study of 181 of 244 patients with cerebral complications among 2523
      surgical cases of infective endocarditis of the Japanese Association of Thoracic
      Surgery. The results showed that 9.7% of all patients with infective endocarditis
      had associated cerebral complications: 108 (44.3%) had active native valve
      endocarditis, 96 (39.3%) had healed native valve endocarditis, and 40 (16.4%) had
      prosthetic valve endocarditis. The hospital mortality of the patients with
      cerebral complications was 11.0% in the group as a whole: 13.9% in active native
      valve endocarditis, 3.1% in healed native valve endocarditis, and 37.5% in
      prosthetic valve endocarditis. Diseased valves included the following aortic
      valve in 55.5%, mitral valve 49.8%, tricuspid valve in 1.3%, and pulmonary valve
      in 1.3%. In 181 patients with cerebral complications, organisms were detected as
      follows: gram-positive cocci in 133 (73.5% [Streptococcus in 85, Staphylococcus
      in 32]), gram-negative in 18 (9.9%), fungus in 11 (6.1%), and unknown in 64.6%,
      cerebral bleeding in 31.5%, cerebral abscess in 2.8%, and meningitis in 1.1%.
      Hospital mortality rate and an exacerbation rate of cerebral complications,
      including related death, according to the interval from onset of cerebral
      infarction to cardiac surgery, were as follows: 66.3% and 45.5% within 24 hours,
      31.3% and 43.8% between 2 and 7 days, 16.7% and 16.7% between 8 and 14 days,
      10.0% and 10.0% between 15 and 21 days, 26.3% and 10.5% between 22 and 28 days,
      and 7.0% and 2.3% over 4 weeks later, respectively. A significant correlation
      existed between the interval and the exacerbation of cerebral complications (tied
      p = 0.008). Preoperative risk factors affecting exacerbation of cerebral
      complications were as follows: (1) severity of cerebral complications (p =
      0.006), (2) intervals (p = 0.012), and (3) uncontrolled congestive heart failure
      as indications for cardiac surgery (p = 0.014). One patient underwent a cardiac
      operation within 24 hours of the onset of cerebral hemorrhage and died of
      cerebral damage. No exacerbations occurred in 10 patients who underwent their
      operation between 2 and 28 days. Nevertheless, exacerbations occurred in 19.0% of
      patients whose operation was done more than 4 weeks later. These data suggest
      that cardiac operations can be done safely 4 weeks after cerebral infarction, and
      if the delay is more than 2 weeks, the exacerbation rate will be around 10%. The
      risk of progression of cerebral damage is still significant 15 days and even 4
      weeks after cerebral hemorrhage.

PMID- 8523889
TI  - Measurement of lung oxygen consumption in a patient after double-lung transplant.

PMID- 8523890
TI  - Supraclavicular lung biopsy.

PMID- 8523891
TI  - Extracardiac modification of the Fontan operation without use of prosthetic
      material.

PMID- 8523892
TI  - Atherosclerotic lesions of the gastroepiploic artery: one case requiring
      postoperative dilation and some interesting postmortem observations.

PMID- 8523893
TI  - Mediastinal thymic cysts: a report of three cases.

PMID- 8523894
TI  - Modulation of alloreactivity in transplant recipients by phenotypic manipulation
      of donor endothelium.

PMID- 8523895
TI  - On dynamic cardiomyoplasty.

PMID- 8523896
TI  - Axillary artery for extracorporeal circulation.

PMID- 8523897
TI  - Neurotrophin receptor proteins immunoreactivity in the rat cerebellar cortex as a
      function of age.
AB  - The influence of age on immunohistochemically demonstrable neurotrophin receptor
      proteins (p75, trkA-, trkB-, and trkC-proteins) was studied in the cerebellar
      cortex of Wistar male rats aged 3 (young), 12 (adult) and 24 (old) months. The
      number of Purkinje neurons displaying p75, trkA- and trkC-like proteins
      immunoreactivity (IR), as well as the intensity of p75 and trkA-like protein IR,
      were significantly reduced in aged rats in comparison with 3 and 12-month-old
      rats. The intensity of trkC-like protein in the cytoplasm of Purkinje neurons
      remained unchanged for all the period studied. Moreover, no significant age
      dependent changes were observed in the density of p75 or trkC-like proteins IR in
      the granule neurons layer. The molecular layer showed faint p75 IR which
      decreased as a function of age. No immunolabelling for neuronal trkB-like
      proteins was observed, but trkB- and trkC-like proteins IR was found in non
      neuronal cells. These results suggest that cerebellar cortex neurons are
      responsive to and/or dependent upon different neurotrophins. Moreover, the age
      dependent impairment in the expression of some neurotrophin receptors in Purkinje
      neurons, but not in the granule neurons, lends support to a role for
      neurotrophins in cerebellar aging.

PMID- 8523898
TI  - Age-related changes in basal dendrite and dendritic spine of hippocampal
      pyramidal neurons (CA1) among SAMP1TA/Ngs--quantitative analysis by the rapid
      Golgi method.
AB  - It has been confirmed that a substrain of the senescence-accelerated mouse
      SAMP1TA/Ngs develops learning disturbance-like behavior at 3 months of age,
      exhibits almost normal behavior at 5 months, and manifests learning disturbance
      at 7 months. The changes with age in basal dendrites and dendritic spines of CA1
      pyramidal neurons were quantitatively evaluated by the Golgi method using male
      SAMP1TA/Ngs. The correlation between the change in learning ability and the
      morphometry was examined. The number of dendritic spines in the 3- and 7-month
      old groups was significantly lower than that in the 5-month-old group. It is
      presumed that the disturbance in acquisition of learning ability at 3 months of
      age is secondary to the immaturity of neurons, while the learning disturbance at
      7 months of age is due to neuronal aging. This substrain, which is characterized
      by the impairment of acquired learning ability due to senescence, is useful as a
      model for studies on human brain dysfunction associated with senescence.

PMID- 8523899
TI  - Evolution of neuronal density in the ageing thalamic reticular nucleus.
AB  - In this paper we present an analysis of the visual sector of the Thalamic
      Reticular Nucleus (TRN) from 3, 6, 18, 24 and 30 month old Wistar rats using
      stereological methods. The volume density (Vv), the number of neurones per
      surface unit (Na) and the neurone numerical density (Nv) showed a progressive
      decrease between the 3rd and the 24th months as the animals aged, whereas a
      significant increase was observed between the 24th and the 30th month, the period
      at which these rodents have fully entered old age.

PMID- 8523900
TI  - Analysis of mortality rate from carcinoma of prostate.
AB  - Age-specific mortality from carcinoma of the prostate was analyzed by drawing a
      line between the value at age 52 years and that at age 87. Slope of the line was
      relatively constant for the pooled years 1962-1966, 1967-1971 and 1972-1976
      (maximum variation from the mean of 4.5%). However, the slope was 17.7% greater
      for the period 1977-1981 and 29.8% over the prior mean in 1987-1992. This was
      explored by two models. Mortality versus age was well described by a power
      function, with an increase in slope noted in the mid-1970s. An exponential growth
      model was also utilized and revealed the existence of a 'change point' around the
      year 1975. Hence, two models are available for further exploring the increase in
      age-specific mortality from carcinoma of the prostate which occurred in the mid
      1970 period.

PMID- 8523901
TI  - Stimulatory effect of saponin from Panax ginseng on immune function of
      lymphocytes in the elderly.
AB  - We used the saponin Rg1 extracted from Panax ginseng to study its effects on
      lymphocytes of 10 young and 19 elderly persons. The proliferative response of
      lymphocytes cocultured for 72 h with PHA and saponin was measured by using MTT
      method and the 3H-TdR incorporation procedure. PHA and Rg1 had stimulative
      effects on the phenotype of lymphocytes (P < 0.001). Rg1 also increased the
      fluidity of lymphocyte membrane of the aged (P < 0.001). The CD25 and CD45RA
      positive cells of lymphocytes in the elderly were lower than those of the young
      people, 8.6% +/- 2.7% vs 10.43% +/- 3.5%; 20.95% +/- 15.5% vs. 50.86% +/- 4.2%,
      respectively. More CD45RO positive cells (41.5% +/- 13.9%) than CD45RA positive
      cell lymphocyte populations were seen in the aged. The CD45RO positive cells of
      the young people were 39.63% +/- 3.2%. We discussed the cause of declined immune
      function of lymphocytes of aged person and the mechanism of the effect of P.
      ginseng on lymphocytes.

PMID- 8523902
TI  - Suppression of age-related changes in mouse hippocampal CA3 nerve cells by a free
      radical scavenger.
AB  - This study was designed to evaluate the relationship between oxygen free radicals
      and age-related morphological changes in hippocampal nerve cells using K-7259
      (N,N' bis[4-(3,4,5-trimethoxyphenyl)butyl] homopiperazine dihydrochloride), a
      known neuro-protective agent. A chemiluminescence assay has shown that this agent
      is a potent free radical scavenger with an IC50 of 1.6 x 10(-5)M. Mice fed diets
      containing 10, 20, 40 mg/kg/day of K-7259, for periods ranging from 25 to 40 or
      50 weeks of age were used as test groups, and 10-, 20-, 30-, 40-, and 50-week-old
      mice fed a standard diet were used as controls. We measured the number and area
      of pyramidal nerve cells within a defined frame in the hippocampal CA3 field
      using an image analyzer and the density of nerve cells by the disector method.
      These values decreased gradually in controls as expected, and the number and area
      yielded a significant difference between control mice at the ages of 10 and 30
      weeks. As compared with the corresponding controls, all test groups had greater
      cell numbers (statistical significance at 40 weeks in the 40 mg/kg/day group) and
      density, while cell areas were greater in all but a 10 mg/kg/day group
      (statistical significance at 50 weeks). In summary, the free radical scavenger K
      7259 forestalled an age-related decrease in the number and size of hippocampal
      CA3 nerve cells, thus suggesting that free radicals play an important role in the
      cellular morphological changes which appear with age.

PMID- 8523903
TI  - Real-time compression of myoelectric data utilising adaptive differential pulse
      code modulation.
AB  - The myoelectric signal, obtained by either surface or needle electrodes, is used
      in many areas of clinical research and diagnosis. The conventional method of
      storing such information is in digitised form on a computer. However, the
      bandwidth of the signal and the required resolution result in large memory
      requirements. Adaptive differential pulse code modulation is investigated as a
      method of reducing the memory requirements for myoelectric data storage. In this
      scheme, a 12-bit sample is reduced to four bits, thus reducing the memory
      requirements by a factor of three. In reality, this compression ratio is closer
      to 4:1 owing to the fact that the widths of most memories are organised as
      multiples of eight bits.

PMID- 8523904
TI  - Real-time measurement of pulse wave velocity from arterial pressure waveforms.
AB  - Instrumentation for the real-time clinical measurement of pulse wave velocity
      (PWV) from intra-arterial pressure waveforms is presented. This time delay
      between pressure waveforms (obtained from two intra- arterial catheter-mounted
      transducers 5 cm apart) is calculated by a transputer using multiple comparisons
      between discrete sections of the waveforms. The method is validated by analysis
      of digital and analogue signals with known time delays and is used to measure
      changes in PWV in the right common iliac artery (RCIA) during infusions of
      acetylcholine (2.4, 24 and 240 micrograms ml-1) in six healthy subjects. The
      system measures the delay between digitally shifted triangular waveforms and
      pressure waveforms to a precision of about 50 microseconds, and it is superior to
      measurements performed by hand using a high-performance digital storage
      oscilloscope. When used to measure the effects of acetylcholine on the RCIA, dose
      dependent reductions in PWV are recorded (-85%, -11.6%, -14.5%). It is concluded
      that the instrumentation enables PWV to be measured with high accuracy and
      precision in real time, if the pressure signals are of high fidelity and the
      relative amplification of the signals is carefully balanced.

PMID- 8523905
TI  - Localisation of myocardial ischaemia from the magnetocardiogram using current
      density reconstruction method: computer simulation study.
AB  - A computer simulation study is performed to investigate the method of current
      density reconstruction to localise myocardial ischaemia. A computer model of the
      entire human heart is used to simulate the excitation and repolarisation process
      in eight topographically different cases of myocardial ischaemia. The associated
      magnetocardiogram is calculated at 37 positions of the KRENIKON biomagnetic
      measurement equipment. The method of current density reconstruction is applied at
      the S-point (the last discernible deviation from the ST-segment at the end of the
      QRS-complex) of the MCG to find characteristics of the myocardial ischaemia
      simulated by the model. The results show that it is possible to determine the
      location of the ischaemia. The current density distribution may be interpreted
      physiologically in terms of the so-called 'injury-current'. This indicates that
      magnetocardiography might be a suitable method for noninvasive ischaemia
      diagnosis, and further investigations of the current density reconstruction
      method for the injury current should be performed on patients with ischaemic
      heart disease.

PMID- 8523906
TI  - Impedance and wave reflection in arterial system: simulation with geometrically
      tapered T-tubes.
AB  - The aortic input impedance is simulated by an asymmetric T-tube model loaded with
      complex loads. A geometric tapering is incorporated to represent the vasculature,
      assuming a triangular distribution of the wave transmission paths. Parametric
      analyses using physiological data demonstrate that the predicted impedance and
      reflection coefficient spectrum (RCS) closely mimic the experimental data. The
      simulation also reveals several significant features. As diameter tapering can
      minimise the presence and influence of wave reflections, the impedance modulus
      stays relatively constant with two distinct minima. The frequency of first
      minimum of impedance modulus is evidence of the tube elasticity and load
      compliance in the lower extremity, and the frequency of second minimum is
      evidence of those in the upper extremity. The high-frequency portion of the
      impedance modulus is affected by the tube elasticity, but not by the load
      compliance. The impedance spectrum at higher frequencies shows no notable
      fluctuations corresponding to a decrease in blood or wall viscosity. Furthermore,
      the low-frequency range in RCS is dominated by the longer lower body tube, and
      the high-frequency range by the shorter upper body tube. This geometrically
      tapered T-tube is considered a more natural model for the description of the
      systemic arterial system.

PMID- 8523907
TI  - Comparison of different oxygen exchange models.
AB  - A functional distribution of coronary volume can be estimated from the response
      of arterio-venous O2 content difference (AVO2) to a flow step. However, the
      results depend on the assumed O2 exchange model. The previously used model
      consisted of a single mixed compartment with O2 exchange (reference model). The
      purpose of this study is to provide an estimate of the errors made in the volume
      estimations by not taking into account factors as flow heterogeneity, different
      mixing sites or Krogh-like O2 exchange. The approach is indirect: the response of
      the AVO2 to a flow step has been calculated with alternative O2 exchange models
      in which factors mentioned are incorporated. These transients are fitted with the
      reference model. The resulting estimated volumes are different from the volumes
      assumed in the alternative models. Large differences are obtained with some of
      the alternative models, e.g. the model with Krogh characteristics. However, these
      models seem unrealistic because capillary pO2 is higher than venous pO2. Only
      small differences in volume are obtained with the more realistic models.
      Therefore, these results indicate that the coronary volumes are approximated well
      by the estimations obtained with the reference model. These volume estimations
      were 9.9 and 3.8 ml 100 g-1 for the O2 exchange vessels and the distal venous
      volume, respectively.

PMID- 8523908
TI  - Bio-acoustic signals from stenotic tube flow: state of the art and perspectives
      for future methodological development.
AB  - To study the degree of stenosis from the acoustic signal generated by the
      turbulent flow in a stenotic vessel, so-called phonoangiography was first
      suggested over 20 years ago. A reason for the limited use of the technique today
      may be that, in the early work, the theory of how to relate the spectrum of the
      acoustic signal to the degree of the stenosis was not clear. However, during the
      last decade, the theoretical basis for this and other biological tube flow
      applications has been clarified. Now there is also easy access to computers for
      frequency analysis. A further explanation for the limited diagnostic use of bio
      acoustic techniques for tube flow is the strong competition from ultrasound
      Doppler techniques. In the future, however, applications may be expected in
      biological tube flow where the non-invasive, simple and inexpensive bio-acoustic
      techniques will have a definite role as a diagnostic method.

PMID- 8523909
TI  - Effects of electrode geometry and combination on nerve fibre selectivity in
      spinal cord stimulation.
AB  - The differential effects of the geometry of a rostrocaudal array of electrode
      contacts on dorsal column fibre and dorsal root fibre activation in spinal cord
      stimulation are analysed theoretically. 3-D models of the mid-cervical and mid
      thoracic vertebral areas are used for the computation of stimulation induced
      field potentials, whereas a cable model of myelinated nerve fibre is used for the
      calculation of the excitation thresholds of large dorsal column and dorsal root
      fibres. The size and spacing of 2-D rectangular electrode contacts are varied
      while mono-, bi- and tripolar stimulation are applied. The model predicts that
      the highest preferential stimulation of dorsal root fibres is obtained in
      monopolar stimulation with a large cathode, whereas dorsal column fibre
      preference is highest in tripolar stimulation with small contacts and small
      contact spacings. Fibre type preference is most sensitive to variations of
      rostrocaudal contact size and least sensitive to variations of lateral contact
      size. Dorsal root fibre preference is increased and sensitivity to lead geometry
      is reduced as the distance from contacts to spinal cord is increased.

PMID- 8523910
TI  - OKAS-3D: optoelectronic jaw movement recording system with six degrees of
      freedom.
AB  - OKAS-3D is a further development of the single floating circle target tracker.
      This tracker consists of a cathode ray tube display, a lens in front of the
      display and a circular light-sensitive photocell placed in the image field of the
      lens. A small circular trace generated on the screen is focused around the
      photocell. The sinusoidal electrical output of the photocell contains all the
      relevant information regarding the position of the photocell relative to the
      image of the circular light trace. This gives the tracker the properties of a
      servo-controller with position feedback. In OKAS-3D three pairs of photocells are
      located on two lightweight frames attached to the upper and lower frontal teeth
      by individually adapted clutches. By using the formulas of rigid body
      mathematics, the motion of any point of the mandible can be reconstructed. The
      system permits a high sampling frequency of at least 300 Hz per photocell co
      ordinate. The noise, linearity and accuracy are better than 0.08 mm, 0.07 mm and
      0.13 mm for points in the lower incisal region, and better than 0.25 mm, 0.17 mm
      and 0.27 mm for points in the condylar region. Thus jaw movements can be recorded
      with a high spatial and temporal resolution.

PMID- 8523911
TI  - Differences in spectral composition between monostrut Bjork-Shiley and
      Carbomedics valves implanted in the aortic position.
AB  - The paper investigates the differences in spectral composition between monostrut
      Bjork-Shiley and Carbomedics valves implanted in the aortic position using a
      modified overdetermined forward-backward Prony's method. Spectral composition of
      the closing sounds produced by these two valves are compared in terms of the e
      number of spectral components and their relative energy. Results show that, for
      both valves, the major spectral components are concentrated below 2 kHz. In the
      case of the Carbomedics valve, it is found that 97% of the total energy lies
      below 120 Hz where the sensitivity of the human auditory system is poor. This is
      one of the main reasons why the Carbomedics valve is acoustically quieter than a
      monostrut Bjork-Shiley valve when in operation. In addition, a clear difference
      monostrut and Carbomedics valves has also been found in the 400 Hz-2 kHz sub
      band. A distinct difference between normal and malfunctioning cases of each
      prostheses has been found in the frequency components beyond 400 Hz. In the
      malfunctioning cases the frequency components in that region move to the lower
      regions of the spectrum and a large part of the energy is concentrated between
      250 and 400 Hz.

PMID- 8523912
TI  - High-quality compression of echographic images by neural networks and vector
      quantisation.
AB  - A compression method is presented for medical images based on neural networks and
      vector quantisation (VQ). The neural net is a perceptron and it is followed by
      some expressly designed VQ algorithms. The method devotes special attention to
      the quality of the reconstructed images and to the reduction of artefacts. The
      compression ratio obtained in the long run with echographic images is greater
      than 50:1 with good quality.

PMID- 8523913
TI  - Non-invasive evaluation of abdominal aortic properties: lumped circuit model and
      estimation of its parameters.
AB  - To non-invasively determine abdominal aortic properties, a five-element lumped
      circuit model was adopted. The model consists of resistance due to blood
      viscosity (R1), inertia of blood flow, compliances of the vessel (C1, C2),
      resistance of the peripheral arteries (R2) and the impedance of the of the
      femoral arteries (termination). Patterns of the central velocity of the upper
      abdominal aorta and the femoral artery are measured by pulsed Doppler
      echocardiography, and contours of flow volume rates are calculated. The pressure
      pattern of the lower limb is recorded by a pulse wave transducer and corrected
      according to sphygmomanometer values. Contours are transformed into respective
      Fourier transform components. The current transfer function is described
      theoretically and calculated from the acquired Fourier components. Values of
      every element are evaluated by the nonlinear least squares method. In 94 subjects
      (17-92 years), the values of each element are estimated. R2 values are greater in
      the elderly group than in the young group and r1 (R1/cm) increased with age. This
      model demonstrates that vessel compliance (C1 + C2 (C1 + C2/cm)) decreases with
      age, and it is suggested that this may be a useful marker of arteriosclerosis.

PMID- 8523914
TI  - Real-time adaptive cancelling of ambient noise in lung sound measurement.

PMID- 8523915
TI  - Multiple scattering effect in transmission pulse oximetry.

PMID- 8523916
TI  - Effects of electrode interface impedance on finite element models of transvenous
      defibrillation.

PMID- 8523917
TI  - Flow in catheterised curved artery.

PMID- 8523918
TI  - Aspects of silicone rubber as encapsulant for neurological prostheses. Part 3:
      Adhesion to mixed oxides.

PMID- 8523919
TI  - Microcomputer-based system for real-time optical imaging.

PMID- 8523920
TI  - Computer-controlled vibrations of a biological subject in the nm range.

PMID- 8523921
TI  - Dedicated low-field MRI: a promising low cost-technique.

PMID- 8523922
TI  - Voltage clamp method for the use of electrical admittance plethysmography in
      human body segments.

PMID- 8523923
TI  - Constructing custom ultrasound transducer clamps for in vitro experiments.

PMID- 8523924
TI  - Angioplasty pressure-volume measurement.
AB  - An instrument has been developed for controlled inflation and deflation of an
      angioplasty balloon. The mean difference between inflation to 800 kPa in air and
      a simulated coronary artery is 71.2 kPa. The repeatability of four
      inflation/deflation cycles is 6.4 kPa with the balloon in air and 9.0 kPa in the
      simulated artery.

PMID- 8523925
TI  - [Prediction of the presence of pneumonia in adults with fever].
AB  - BACKGROUND: This study was performed to define what clinical and analytical
      variables were significantly associated with the presence of pneumonia in febrile
      patients. A predictive model which may rationalize radiologic explorations is
      presented. METHODS: A prospective study was carried out in two Emergency
      Departments in Madrid, Spain. One hundred forty-one patients presenting fever of
      more than 48 hours in evolution with symptomatology of the lower airway or
      without focal data were included. Following anamnesis, physical exploration and
      elemental hemogram the physician established a tentative diagnosis. Subsequently,
      on observation of thorax X-ray definitive diagnosis was made. RESULTS: Thirty
      eight percent of the patients had pneumonia. The variables which were
      significantly associated with the presence of pneumonia were: history of smoking
      (odds ratio [OR] 2.06), alcohol abuse (OR 3.18), chronic obstructive
      bronchopneumopathy (OR 4.35), respiratory symptoms (OR 5.73), cough (OR 5.37),
      expectoration (OR 2.08), dyspnea (OR 7.03), pleural pain (OR 13.38), pathologic
      auscultation (OR 7.46), leukocytes (OR 6.34) and neutrophilia (OR 8.10). Clinical
      prior to radiologic diagnosis showed a sensitivity of 45.3% and specificity of
      93.2%. Pneumonia was demonstrated in 10% of the cases with respiratory
      symptomatology with normal auscultation and without neutrophilia. A logistic
      regression model is proposed for the diagnosis of pneumonia. CONCLUSIONS:
      Clinical judgment prior to observation of radiography has a low sensitivity in
      the improvement in clinical judgment.

PMID- 8523926
TI  - [Subcutaneous administration of desmopressin to plasma donors: a controlled
      study].
AB  - BACKGROUND: The aim of the present controlled study was to assess the effect of
      subcutaneous administration of desmopressin acetate (DDAVP) on the yield of
      Factor VIII (FVIII) and von Willebrand Factor (vWF) obtained in cryoprecipitates
      after plasmapheresis collection. SUBJECTS AND METHODS: Fifteen plasma donors
      underwent twice plasmapheresis collections using an "Autophereses C. model A-201"
      and cryoprecipitates were prepared using standard methods. In every subject of
      study one of the procedure was performed 35 min after subcutaneous administration
      of DDAVP (0.3 micrograms/kg), obtained from a highly concentrated preparation of
      the drug (40 micrograms/ml). Prior to the other apheresis procedure no chemicals
      were administered. Evaluation of FVIII and vWF levels was performed in peripheral
      blood samples obtained at different time points and cryoprecipitates product
      samples. RESULTS: Administration of DDAVP led to two-fold increase the yield of
      FVIII and vWF immediately before the performance of plasmapheresis. DDAVP
      stimulation resulted in an increase in the yield of FVIII and vWF in
      cryoprecipitates, compared with levels in the absence of the drug (703 +/- 53 and
      768 +/- 51 U versus 227 +/- 12 and 362 +/- 20 U, respectively). No adverse
      effects but flushing were observed after DDAVP administration. CONCLUSIONS:
      Subcutaneous administration of DDAVP prior to plasma collection is a safe method
      to improve drastically the content of FVIII and vWF in cryoprecipitates. This
      procedure should be considered as an useful tool to help in providing self
      sufficiency of plasma.

PMID- 8523927
TI  - [The impact of AIDS in the global mortality in Catalonia, 1981-1993].
AB  - OBJECTIVES: To compare the evolution of the principal causes of death in
      Catalonia, Spain and to assess the impact of AIDS as a contributing factor to the
      increase of mortality in young people in Catalonia. METHODS: Data from the
      mortality register of Department of Health in Catalonia has been used. We have
      compared the principal causes of death in Catalonia for the global population and
      for the group of 20 to 39 year olds. We have calculated the potential years of
      life lost (PYLL) between the ages of 13 to 65. RESULTS: Since the first case of
      AIDS in 1981, AIDS has been the cause of death with the most important increase
      for the global population in Catalonia. AIDS is the sixth cause of death and the
      first cause of PYLL. For the young population in Catalonia (aged 20-39) AIDS
      became, in 1993, the first cause of death. From 1992 to 1993 the PYLL due to AIDS
      increased 5% in men and 51% in women. CONCLUSIONS: The present situation has led
      AIDS being the first cause of death among young population. The collaboration
      between mortality registers and AIDS registers is absolutely essential to assess
      more accurately the impact of AIDS on the mortality of population.

PMID- 8523928
TI  - [Fever. Guess what is behind it].

PMID- 8523929
TI  - [Concept and projection of infectiology].

PMID- 8523930
TI  - [Amebic liver abscess: review of 13 cases].
AB  - Amebian hepatic abscess (AHA) is the most frequent extraintestinal localization
      of infection by Entamoeba histolytica. Despite being a disease mainly of tropical
      zones, it is currently also observed with higher frequency in Spain. Thirteen
      cases of AHA diagnosed in the authors' hospital over the last 11 years were
      retrospectively analyzed comparing the data in this series with that of other
      published series and undertaking a review of this subject. The diagnosis of AHA
      was established on the basis of the clinical picture together with specific
      positive serology and compatible echographic imaging. The series was composed of
      9 males and 4 females with a mean age of 38.7 years (range 25-55). Five were
      Spanish, and 8 were immigrants from tropical countries. In 61.5% of the cases
      echographically guided aspiration puncture was performed with placement of
      percutaneous drainage being carried out in 38%. Eighty-five percent of patients
      were treated with more than one amebicide drug (metronidazole or tinidazole
      together with chloroquine and dehydroemetine). Luminal amebicides were
      administered lastly. Laparotomy was required in 3 cases due to the presence of
      complications. No deaths were observed.

PMID- 8523931
TI  - [Effectiveness of condoms in the prevention of HIV infection in partners of
      seropositive subjects].

PMID- 8523932
TI  - [Fever, anemia and decompensation of liver disease in a 9-year-old child with
      congenital immunodeficiency].

PMID- 8523933
TI  - [Lipoprotein(a) increase in intravenous drug addicts with HIV(+) infection].

PMID- 8523934
TI  - [Determination of dehydrogenase C4 lactate in spermatozoa of infertile men].

PMID- 8523935
TI  - [Acute hydrocephalus in Listeria monocytogenes meningitis].

PMID- 8523936
TI  - [Agranulocytosis induced by calcium dobesilate].

PMID- 8523937
TI  - [Are microbiological studies necessary before starting tuberculosis
      chemoprophylaxis?].

PMID- 8523938
TI  - [Traffic accidents in the Spanish population].
AB  - BACKGROUND: The aim of this study is to analyze the accident phenomenon in
      general, and in the particular case of road accidents, using to this purpose the
      1993 National Health Survey. METHODS: The National Health Survey of 1993 was
      carried out in 26,334 inhabitants (21,084 adults > 16 years of age and 5,250
      children). This survey tends to study the characteristics and distribution of the
      morbidity by the Spanish population. RESULTS: 7.8% of the population had suffered
      an accident in the last twelve months. 1.6% has suffered a road accident. Road
      accidents were more common in men and in the 11-30 age group. 52.1% out the
      casualties in road accidents were assisted in an emergency department. The most
      common injuries were bumps and contusions (53.4%) and fractures and wounds
      (42.4%). CONCLUSIONS: Road accidents are frequent in the Spanish population,
      specially in men and young adults; also, they often need to use sanitary
      services.

PMID- 8523939
TI  - [Allogeneic bone marrow transplantation in chronic myeloid leukemia. The clinical
      results and risk factors in 70 patients].
AB  - BACKGROUND: The 10 year experience of a single center performing allogeneic bone
      marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is
      analyzed. METHODS: Seventy patients transplanted for CML between November 1982
      and October 1992 were evaluated. Fifty-two patients were in the first chronic
      phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second
      chronic phase. The combination of cyclosporin and methotrexate was the most
      commonly used prophylactic schedule for graft versus host disease (GVHD) (60
      cases) and T depletion was not performed in any case. The combination of
      cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients
      with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide
      (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier
      limit product method. The prognostic factors influencing survival, disease free
      period and relapse were evaluated by Cox multivariate models of proportional
      risk. RESULTS: Actuarial survival at four years was 40% (95% Cl: 26-58%).
      Multivariate analysis selected variables associated with lower survival, the
      presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26)
      and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate
      analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR:
      1.91) to be associated to a higher probability of relapse. In a separate analysis
      of the 48 patients transplanted in chronic phase who received cyclosporin and
      methotrexate, the disease free survival was longer for those under the age of 30
      years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted
      from a male donor (64.6% vs. 30%). CONCLUSIONS: Advanced phase of the disease,
      the presence of acute graft versus host disease and the age and female sex of the
      donor are the main factors associated to shorter survival in allogeneic bone
      marrow transplant for chronic myeloid leukemia. In contrast, the presence of
      chronic graft versus host disease decreases the possibilities of relapse.

PMID- 8523940
TI  - [The perception of improvement in asthma].
AB  - BACKGROUND: The capacity of stable asthma patients to recognize the presence of
      air flow obstruction, treatment improvement and daily variations was studied.
      METHODS: Placebo and 500 micrograms of inhaled terbutaline for two consecutive
      days were administered to 39 patients. The subjective impressions were compared
      with spirometric results. RESULTS: Thirty patients presented obstruction of which
      7 reported to be asymptomatic and 9 presented normal spirometry of which 3
      reported to be symptomatic. Fifty-four percent (21) did not correctly recognize
      whether they improved with the medication either of the two days. Eleven patients
      reported improvement with placebo without significant spirometric changes.
      Eighteen preferred terbutaline and 5 the placebo while 16 were indifferent out of
      whom 7 (43%) had improved with only the bronchodilator. The FEV1 difference
      between the two days was > 10% in 18 patients of which this was not perceived in
      10. CONCLUSIONS: Objective controls are necessary for the evaluation and follow
      up of patients with stable asthma.

PMID- 8523941
TI  - [Fever of unknown origin in HIV infection. New facets of an old problem].

PMID- 8523942
TI  - [Human ecology: a judicial statute of the human body].

PMID- 8523943
TI  - [Intense neutropenia of 14 years duration as the only manifestation of a
      myelodysplastic syndrome].
AB  - Myelodysplastic syndromes (MDS) are a group of acquired hemopathies characterized
      by peripheral cytopenias due to ineffective hematopoiesis and a high risk of
      transformation into acute non lymphoblastic leukemia (ANLL) which, in most cases,
      usually occurs from 6 months to 4 years after diagnosis. A patient with extreme
      neutropenia with intense dysgranulopoiesis as the only manifestations of MDS is
      described. The patient was controlled over 14 years and presented multiple
      infectious episodes, in various locations, throughout the evolution, some being
      very severe and generally caused by gram-negative germs. Likewise, during this
      time the patient received different treatments (oxymetholone, prednisone and
      lithium carbonate) with no hematologic response being observed. The leukocyte
      count remained around 3 x 10(9)/L with a mean proportion of neutrophils of 12%
      with no variations being found in the bone marrow aspirates carried out
      throughout the evolution (total of 9). At 14 years the diagnosis of MDS evolved
      to ANLL. The patient died shortly after the acute transformation due to
      respiratory failure secondary to bilateral pneumonia. In this case three peculiar
      features are of note: the almost exclusive involvement of the granulopoietic
      series without either anemia or thrombocytopenia, the long evolution of AREB,
      with acute transformation 14 years after diagnosis and the severity of the
      infections, among which recurrent lingual granulopenic ulcers were of note.

PMID- 8523944
TI  - [The clinician up to date. A danger for the patient?].

PMID- 8523945
TI  - [The cardiovascular effects of alcohol].

PMID- 8523946
TI  - [The safety of treatment with intravenous gamma-globulin in patients with primary
      hypogammaglobulinemias].

PMID- 8523947
TI  - [Viral hepatitis A: more cases in young adults].

PMID- 8523948
TI  - [Infectious endocarditis of the native valve].

PMID- 8523949
TI  - [Anticoagulation in auricular fibrillation].

PMID- 8523950
TI  - [Corticoid treatment in Castleman's disease].

PMID- 8523951
TI  - [Internuclear ophthalmoplegia as the initial manifestation of Lyme disease].

PMID- 8523952
TI  - [Survival in cancer of the breast in Zaragoza (1960-1990) in relation to age,
      clinical stage and period of time of the diagnosis].
AB  - BACKGROUND: The characteristics of a population based series of 3,066 women
      diagnosed with breast cancer collected by the Cancer Registry of Zaragoza, Spain
      from 1960 to 1990 are herein described. Gross short and long term survival, as
      well as specific survival were estimated according to age at diagnosis, tumor
      stage and the period in which the patient was diagnosed. METHODS: Every patient
      was followed up to verification of death or to the latest information available
      up to January 1, 1991. Diagnosis specified in writing in the clinical history and
      support by surgical or anatomopathologic reports were required. The data
      concerning place and site of residence and the vital status of the cases were
      verified by the municipal and civil registries, death certificates and burial
      registries. The survival curves were estimated by the Kaplan-Meier method, and
      short and long term survival, by age and tumor stage at diagnosis and the
      diagnostic period were also evaluated. RESULTS: Gross survival was estimated as
      89.1% in the first year, 50.9% at 5 years, and 34.7%, 28.4% and 20.0% at 10, 15,
      20 and 25 years, respectively. Survival at 5 years according to TNM clinical
      stage classification (UICC-AJC 1978) was 90% for stage I, 69.5% for stage II,
      44.6% for stage III and 20.6% for stage IV. The cases diagnosed between 1980 and
      1990 presented better survival than those previously diagnosed. The differences
      were statistically significant in all the cases (p < 0.001, log-rank test).
      CONCLUSIONS: A slight improvement has been observed in the survival of women
      diagnosed with breast cancer in Zaragoza, Spain during the study period. Despite
      of that fact, the survival rates were worse than those observed in other
      countries with similar socioeconomic development.

PMID- 8523953
TI  - [Somatization disorders in primary care: differential clinical aspects. Study
      Group of Psychic and Psychosomatic Morbidity of Zaragoza, Primary Care Section].
AB  - BACKGROUND: To identify specific sociodemographic and psychopathological features
      of somatization disorder (SD) patients in relation to other patients with
      psychiatric and organic morbidity in primary care (PC) setting. METHODS: A group
      of SD patients from PC was compared with other two control groups: the first one
      made of patients with psychiatric morbidity (with or without organic disease) and
      the second group of patients with only organic disease without psychiatric
      morbidity. Polivalent standardized psychiatric interview (PSPI), a specific
      psychiatric interview for PC settings, was used as diagnostic instrument.
      RESULTS: 1) there is a female predominance in SD statistically significant
      compared with organic patients and with a trend to significance in relation to
      psychiatric patients. Age, marital status and educational level show no
      significant differences among the groups; 2) in relation to psychopathology, SD
      patients show, in relation with organic patients, statistically higher levels in
      all items measured by PSPI. On the contrary, SD overwhelmed psychiatric patients
      in just four items: somatic symptoms, fatigue, reported anxiety and hystrionism
      as well as sexual problems and lack of social support, and 3) high psychiatric
      morbidity (85%) in SD, most of them affective and anxiety diagnosis, make it
      difficult to differentiate from the other patients suffering from psychiatric
      morbidity in PC. CONCLUSION: Patients with SD show a very different profile
      compared with those with organic disease in relation to psychiatric symptoms and
      social problems. On the other hand, when compared with patients with psychiatric
      disorders, differences are rather scarce. In addition, affective and anxiety
      comorbidity associated make it difficult the diagnosis. For this reason, the use
      of screening instruments for SD seems mandatory.

PMID- 8523954
TI  - [Giant cell arteritis. A study of 191 patients].
AB  - BACKGROUND: The aim of the present was to study the clinical features of a wide
      series of patients with giant cell arteritis (GCA) diagnosed with accurate
      criteria and to evaluate the sensitivity of the criteria proposed by the ACR for
      classification of GCA. METHODS: A retrospective analysis of 191 patients with
      GCA, 184 of whom were diagnosed by biopsy and 7 due to their clinical
      manifestations was carried out. RESULTS: The age was 73 +/- 7 years with the most
      frequent symptoms being headache (87%), abnormalities in the temporal arteries
      (75%), general malaise (60%), rheumatic polymyalgia (49%) and mandibular
      claudication (40%). The frequency of GCA was equal in both genders although the
      most complex syndrome was observed in women with a greater frequency of
      polymyalgia (p < 0.005), jaw claudication (p < 0.01) and anemia (p < 0.01). The
      patients with polymyalgia were characterized by a predominance of the polymyalgic
      syndrome in the initial phases and a higher frequency of amaurosis. Out of 47
      patients with amaurosis, 23 remained with permanent unit or bilateral blindness.
      Unilateral biopsy of the temporal artery was diagnosed in 91% of the cases (CI
      95%; 86 to 95%) increasing to 96.3% (CI 95%; 92 to 98%) on biopsy of both
      arteries. Ninety-eight percent of the patients (CI 95%; 95 to 99%) had 3 or more
      GCA criteria for classification as GCA. CONCLUSIONS: The clinical manifestations
      of giant cell arteritis in Spain, with the exception of an equal frequency in
      both sexes, are similar to that described in other series of patients selected
      with strict criteria. The present data confirm the sensitivity of the criteria
      proposed by the ACR for the classification of giant cell arteritis although its
      application does not avoid the need for temporal artery biopsy for diagnosis.
      Unilateral biopsy is usually suffice in most of the cases.

PMID- 8523955
TI  - [Is it possible to cure cancer of the breast?].

PMID- 8523956
TI  - [Evaluation of scientific evidence].

PMID- 8523957
TI  - [Diagnosis of Cushing's disease in pregnancy].
AB  - The Cushing syndrome during pregnancy is very infrequent, being even more so that
      of hypophysary etiology despite corticotropic adenomas being more prevalent in
      fertile-aged women. Its diagnosis is difficult since it may be confused with the
      physiologic alterations of the cortisol and the ACTH which occur during
      pregnancy. The treatment is controversial. In the cases reported to date,
      pregnancy represented a worsening of the picture. The case of a patient diagnosed
      with Cushing disease during the first trimester of pregnancy is presented. The
      hypercorticism improved clinically and biochemically during the pregnancy with no
      maternofetal complications observed. The disease activity continued following
      delivery.

PMID- 8523958
TI  - [71-year-old male with cholelithiasis and icterus of 1 month development].

PMID- 8523959
TI  - [Imported paracoccidioidomycosis. Apropos of 2 cases].

PMID- 8523960
TI  - [Diarrhea associated with Clostridium difficile and Salmonella enteritidis in a
      patient with HIV infection].

PMID- 8523961
TI  - [The update code in the use of MEDLINE].

PMID- 8523962
TI  - [Contribution of the pharmaceutical industry to articles of clinical
      investigation of drugs].

PMID- 8523963
TI  - [Angiitis and benign lymphocytic granulomatosis].

PMID- 8523964
TI  - [Organization of palliative care].

PMID- 8523965
TI  - [Antifungal activity of fluconazole in vitro].
AB  - The susceptibility of 97 fungal strains to fluconazole was evaluated using the
      dilution method. Forty-three of the strains were C. albicans, fifty-three other
      Candida species and one S. cerevisiae. The MIC values varied from 0.1 mg/l to 100
      mg/l. However, the growth of 75.2% of the strains was considerably inhibited at
      0.1 mg/l. Forty-nine strains were tested using both the dilution and disk
      diffusion methods. The findings were consistent. The latter method may be
      performed on YNB medium and is of practical value.

PMID- 8523966
TI  - [Diagnostic value of the latex test (Pyloriset) for detection of Helicobacter
      pylori antibodies in adult patients with upper digestive tract diseases].
AB  - The biopsy specimens and sera from 269 adult patients referred for gastroscopy
      were examined for Helicobacter pylori infections. The bacteriologic studies
      included: Gram smears, urease test and culture methods of biopsy specimens,
      biochemical tests for identification of isolates and their sensitivity testing to
      17 chemotherapeutics. The biopsy specimens were examined histopathologically
      also. For demonstration of specific antibodies the latex test (Pyloriset, Orion
      Diagnostica, Finland) was used. Biopsy--cultures were positive for H. pylori in
      171 (63.6%) cases, biopsy--urease test in 149 (55.4%) and Gram smears in 163
      (62.8%). A total of 193 (71.7%) positive sera with latex were found. The
      sensitivity and specificity of the latex test as compared with the culture
      method, biopsy--urease test and Gram smears was 80.7% and 43.9%, 80.5% and 39.2%
      or 79.8% and 40.6% respectively. All three direct diagnostic methods were
      positive in 122 (45.4%) patients, 101 (82.8%) of them were positive with the
      latex test. Only in 33 (19.3%) patients with positive biopsy--culture for H.
      pylori anti-H. pylori antibodies were not observed. On the other hand, among 75
      patients with negative all direct methods for H. pylori infections 39 (52.0%) of
      them were positive with the latex test. The latex test was also positive in 56
      (54.9%) sera among 102 blood donor tested by us but this value was lower, in
      trems of statistical significance than in patient sera. In conclusion, the latex
      test may be useful as a screening serological test for the diagnosis of patients
      with H. pylori infections and for epidemiological studies.

PMID- 8523967
TI  - [Phosphatidylinositol specific phospholipase C (PI-PLC) in differentiation of
      Listeria monocytogenes and Listeria innocua].
AB  - Listeria strains were investigated as regard: the production of PI-PLC and
      lecytinase, haemolytic and CAMP activity survival in mouse tissues. Although all
      the examined L. monocytogenes strains produced PI-PLC, they showed a very
      different activity of this enzyme. It was surprising that one of the four L.
      innocua strains demonstrated a weak activity of PI-PLC. L. monocytogenes bacteria
      with strong PI-PLC activity survived in mouse spleens for a much longer period of
      time than L. monocytogenes microbes with only a weak production of this enzyme.
      However, L. innocua bacteria producing some PI-PLC were quickly eliminated by
      infected mice.

PMID- 8523968
TI  - [Potential pathogenic throat bacterial flora in acute successive pharyngitis and
      tonsillitis in children].
AB  - The purpose of this work was to determine the frequency of occurrence of S.
      aureus, H. influenzae, H. parainfluenzae, beta-hemolytic streptococci,
      Enterobacteriaceae spp. and nonfermenting rods in a group of children suffering
      from acute successive pharyngitis and tonsillitis. Specimens were taken during
      three acute occurrences and twice after treatment from first and second acute
      occurrences. S. aureus was isolated from the throats of 55.1%-62% of the sick
      children. H. influenzae and H. parainfluenzae were isolated from about 22% to
      over 40% of the sick children, beta-haemolytic streptococci were isolated from
      10.3%-16.2% of the sick children and Enterobacteriaceae spp. were isolated from
      the throats of 6.1%-16.25% of the sick children. Nonfermenting rods were isolated
      from only one sick child. Two or more possible bacterial pathogens were isolated
      from several sick children. Among them S. aureus with H. influenzae or with H.
      parainfluenzae or with beta-haemolytic streptococci were most often isolated.
      After treatment of these children, S. aureus, H. influenzae, H. parainfluenzae
      were more rarely isolated from the throat, and beta-haemolytic streptococci or
      Enterobacteriaceae spp. were isolated occasionally. Similarly, after treatment
      mixed potentially pathogenic bacterial flora were more rarely seen.

PMID- 8523969
TI  - [Evaluation of conventional and new generation tests for testing the humeral
      response to Mycoplasma pneumoniae antigens in natural infection in humans. I.
      Occurrence and level of mycoplasma antibodies in clinically healthy subjects].
AB  - The aim of the first stage of investigation was to determine, using the
      complement fixation test (CFT), immuno-electroprecipitation test (IEPT) and
      ELISA, the level of mycoplasmal antibodies in serum samples obtained from 114
      clinically healthy persons (49 samples from children and youth up to 20 and 65
      samples from blood donors). On the basis of obtained findings, antibody titer
      assumed to be diagnostically significant was determined on the means + 3 SD level
      in each test. Thus in the CF test the assumed titer > or = 20, in the IEP test-
      titer > or = 2, in the ELISA-IgA--titer > or = 100, in the ELISA- IgG--titer > or
      = 1600, in the ELISA-IgM--titer > or = 1200, in the ELISA -IgA + G + M--titer >
      or = 3200. The study allowed to establish that on with age the level of
      mycoplasmal antibodies in immunoglobulin of classes A and G rose while the titer
      of these antibodies of class IgM remained on the same level in persons up to 20
      and then decreased almost twice in adults. It was also found that in all age
      groups the mean values of titer of antibodies against M. pneumoniae calculated
      for each test were lower than titer assumed to be diagnostically significant.

PMID- 8523970
TI  - [Susceptibility of bacteria isolated from clinical material to ciprofloxacin].
AB  - The aim of the study was to evaluate susceptibility to ciprofloxacin of bacteria
      species isolated from different specimens of clinical materials. The investigated
      strains (830) were identified using conventional methods. The antibacterial
      activity of ciprofloxacin was studied by the method of drug dilution in Mueller
      Hinton agar. Among aerobic bacteria, only 5 strains (0.6%) were resistant to
      ciprofloxacin in concentration 4 micrograms/ml; two belonged to E. coli species,
      two to S. aureus and one was a Streptococcus group B., Corynebacterium sp. MIC90
      = 0.12 microgram/ml turned out to be most resistant, next, Gram-negative rods
      MIC90 = 0.5 microgram/ml, coagulase-negative and positive staphylococci and
      Neisseria sp. MIC90 = 1.0 microgram/ml. Enterococcus faecalis and anaerobes were
      the least susceptible to ciprofloxacin. Their MIC90 was 2 and 16 micrograms/ml
      respectively. Among 20 anaerobic strains, up to 10 were resistant to
      ciprofloxacin, mainly from Bacteroides and Clostridium genus.

PMID- 8523971
TI  - [Evaluation of conventional and new generation tests for testing the humeral
      response to Mycoplasma pneumoniae antigens in natural infections in humans. II.
      Occurrence and level of mycoplasma antibodies in patients with respiratory tract
      infections].
AB  - The aim of the study was to observe the frequency of occurrence of mycoplasmal
      antibodies detected by the complement fixation test (CFT),
      immunoelectroprecipitation test (IEPT) and ELISA in selected groups of patients
      with respiratory tract infections and to determine the dependence of these
      antibodies on the age of patients and length of illness. 521 serum samples
      collected from 404 persons were examined; 378 samples were obtained from 276
      patients with pneumonia and 143 from 128 patients with upper respiratory tract
      infections. Additionally, serum samples from 50 patients with B. pertussis were
      investigated in this section of the study as a control test to demonstrate the
      specificity of the tests. It was established that in patients with pneumonia
      mycoplasmal antibodies are, as a rule, detected in much higher titers than in
      patients with upper respiratory tract infections. On with age, the level of
      mycoplasmal antibodies detected in all the three tests rose in the examined
      patients. In the highest titers antibodies against M. pneumoniae were detected in
      adults within the age 21-50. As a rule mycoplasmal IgM antibodies reached a level
      2-3 times higher than IgG antibodies. It was also shown that already during the
      first week of illness antibodies against M. pneumoniae determined by the CFT,
      IEPT and ELISA in the sera of the examined persons are higher than the level
      known to be diagnostically significant. During the second week of illness IgA and
      IgM antibodies have a particularly high titer while the growth of titer of IgG
      antibodies is relatively small. A very high level of IgM, along with progressive
      growth of IgG antibodies and the related gradual decrease of the index value
      IgM/IgG, was observed in the serum of patients up to the 4th week of illness. In
      some cases, in titer known to be diagnostically significant, this high level was
      present even many months after the appearance of disease symptoms. Antibodies
      against M. pneumoniae in class of immunoglobulin A disappeared the fastest. Thus
      it is believed that demonstrating their characteristics dynamics or detecting
      these antibodies in the patient's serum in the titer assumed to be diagnostically
      significant can indicate an acute stage of illness.

PMID- 8523972
TI  - [Evaluation of conventional and new generation tests for testing the humeral
      response to Mycoplasma pneumoniae antigens in natural infection in humans. III
      Use of ELISA, complement fixation and immunoelectroprecipitation tests in
      diagnosis of Mycoplasma pneumoniae infections--comparative analysis].
AB  - Agreement of the results of determining antibodies against M. pneumoniae was
      evaluated by the ELISA, complement fixation test (CFT) and
      immunoelectroprecipitation test (IEPT) in serum samples from 685 persons
      including 571 patients with respiratory tract infections and 114 clinically
      healthy subjects. Assuming the CF to be the reference test, a very high
      correlation exceeding 0.95 was found, on the basis of the calculated correlation
      coefficient, between the results of the CF and IEP tests and the CFT and ELISA in
      all immunoglobulin classes. The highest sensitivity (92.3%) was displayed by the
      ELISA in relation to the CF test when determining mycoplasmas antibodies of IgM
      and IgA + G + M classes and slightly lower sensitivity by the IEPT and ELISA when
      determining of IgG (83% and 82.1% respectively). The lowest sensitivity was
      displayed by the ELISA when determining mycoplasmal antibodies of IgA class
      (53.4%). Specificity of both the tests was high and exceeded 92%. Highest
      agreement of CFT and ELISA was obtained when detecting mycoplasmal antibodies in
      diagnostically significant titer in the M and A + G + M immunoglobulin classes (>
      92%) while lowest agreement, although statistically significant, was obtained
      when detecting IgA antibodies (74.7%).

PMID- 8523973
TI  - [Viral validation of the bio-globulin production process].
AB  - Intravenous human immunoglobulin of domestic production was subjected to
      validation studies. Tests were performed in the system of model viruses for
      pathogenic factors of the B and C types of hepatitis. For simulated
      immunoglobulin infections two lipid-enveloped viruses were chosen: the first DNA
      virus pseudorabies PR-75 (model for HBV) and the second-RNA virus Sindbis (model
      for HCV). The survival of viruses in particular stages of bio-globulin production
      was checked, showing that pepsin digestion led to full inactivation of both
      viruses. The total reduction of infective titers of model viruses during the
      whole process exceeded 10 logs. Thus we can conclude that the process of bio
      globulin manufacturing ensures the elimination and inactivation of lipid
      enveloped viruses.

PMID- 8523974
TI  - [Detection of Giardia antigens in feces by immunoenzymatic method; advantages and
      disadvantages of commercially available diagnostic kits].
AB  - The results of routine microscopical examination of faeces for infection with
      Giardia were compared with those obtained by immunoenzymatic investigation for
      stool antigens of the parasite, using tests currently available on the Polish
      market. It was found that the results of microscopical examination were very
      consistent with the results of immunoenzymatic tests of the following
      manufactures: Alexon, LMD Labs and Dialab. The above tests may be used as a sole
      diagnostic method for epidemiological or follow-up studies, however, they cannot
      replace microscopical examination.

PMID- 8523975
TI  - Potential schemes for residency manpower reductions.

PMID- 8523976
TI  - Atypical mycobacterial otomastoiditis.

PMID- 8523978
TI  - Secondary tobacco smoke and preventive and protective measures.
AB  - The American Academy of Otolaryngology--Head and Neck Surgery has been concerned
      about the effect of environment degradation on health. There is particular
      interest in the deleterious health effects of secondary smoke. This report
      reviews the recent literature regarding passive smoke and clinical disorders and
      discusses management strategies.

PMID- 8523977
TI  - Advantages and disadvantages of three-dimensional computed tomography
      intraoperative localization for functional endoscopic sinus surgery.
AB  - Intraoperative three-dimensional computed tomography (3-D-CT) localization has
      been available for use during functional endoscopic sinus surgery (FESS) for
      several years, although relatively few otolaryngologists operate in conjunction
      with this technology. Proponents of intraoperative localization believe that
      operating with stereotaxis enhances surgical precision and reduces complications.
      A 1-year review was conducted at the University of Pennsylvania from January 1994
      through January 1995. During this period 5% of sinus operations were performed in
      conjunction with intraoperative localization. The advantages and disadvantages of
      using intraoperative localization were evaluated for each case. Also examined
      were type and indication for surgery, anesthesia used, added time, and cost.
      Overall, intraoperative localization was found to be helpful when anatomy was
      distorted or obscured. However, selecting patients who may have benefited from
      localization was often not possible using preoperative data. Ideally,
      localization should be available for all FESS. Criteria are outlined which will
      need to be met prior to localization becoming a significant aspect of FESS.

PMID- 8523979
TI  - Sensory recovery in noninnervated free flaps for head and neck reconstruction.
AB  - Recent studies have reported sensory recovery in innervated ("sensate")
      microvascular free flaps used for oromandibular reconstruction. To evaluate the
      efficacy of sensate free flaps used for head and neck reconstruction, the natural
      outcome of noninnervated flaps must be known. Data on the natural recovery of
      sensation in noninnervated head and neck free flaps are lacking in the
      literature. This study evaluates the degree of spontaneous sensory reinnervation
      in noninnervated microvascular free flaps used for reconstruction of a variety of
      head and neck defects. Eighteen flaps were evaluated--9 fibula osseocutaneous and
      9 radial forearm. The fibula flaps were used to reconstruct composite defects of
      the mandible and oral cavity mucosa. The radial forearm flaps were used to
      reconstruct defects resulting from floor of mouth resection (3), total
      glossectomy (2), pharyngectomy (1), full-thickness cheek (1), and facial skin
      (2). Sensation to pinprick, light touch, and temperature discrimination were
      tested over the skin paddle at time intervals ranging from 6 to 24 months. The
      pattern of sensory reinnervation in these noninnervated flaps over time and by
      location is discussed.

PMID- 8523980
TI  - P-glycoprotein expression in the squamous cell carcinoma of the tongue base.
AB  - P-glycoprotein (PGP), which is a product of the multidrug resistance gene (MDR1),
      is an active transmembrane efflux pump responsible for detoxifying normal cells
      as well as rendering tumor cells resistant to chemotherapy. It has also been
      implicated to be expressed by more aggressive cancers. It has not been well
      described in squamous cell carcinoma of the head and neck. In this investigation,
      an attempt was made to characterize advanced squamous cell carcinoma of the base
      of tongue with respect to expression of PGP. Using immunohistochemical techniques
      two anti-PGP monoclonal antibodies (JSB1 and C494) were used to detect PGP in
      these lesions, and an attempt was made to correlate levels of PGP staining and
      various tumor parameters. Usefulness of PGP in predicting survival and time to
      recurrence was also examined for these advanced lesions. All 33 base of tongue
      lesions showed staining for PGP with these monoclonal antibodies. This was the
      first study examining utility of C494 in detecting PGP in squamous cell carcinoma
      at this site. Increased level of PGP expression was seen in better-differentiated
      tumors as well as in tumors with diploid DNA. A trend of higher PGP expression
      and decreased survival emerged. This may represent a true relationship, but
      inherent heterogeneity of PGP expression within cells cannot be excluded. Both
      antibodies examined appear to be useful in the investigations of PGP distribution
      in squamous cell carcinomas of the head and neck sites by immunohistochemical
      techniques. Prognostic value of the level of PGP expression remains to be seen.

PMID- 8523981
TI  - Repair of chronic tympanic membrane perforations with long-term epidermal growth
      factor.
AB  - Chronic tympanic membrane (TM) perforation is a common problem worldwide. Recent
      reports have shown epidermal growth factor (EGF) to stimulate healing in
      approximately 80% of chronic TM perforations in chinchillas when applied in three
      doses over 1 week. The objective of this controlled study is to evaluate the
      efficacy of long-term EGF in the closure of TM perforations. Chronic chinchilla
      TM perforations were treated with EGF for up to 6 weeks. One hundred percent (17
      of 17) of treatment group perforations completely healed. However, two new
      findings with this long dosing scheme were reperforation on long-term follow-up
      and three TMs with cholesteatomas. It is likely that reperforation was due to a
      progressive thinning seen with prolonged EGF application. Long-term EGF use is
      not recommended for the treatment of TM perforations because of possible wound
      healing impairment and possible cholesteatoma induction.

PMID- 8523982
TI  - Functional magnetic resonance imaging of the central auditory pathway following
      speech and pure-tone stimuli.
AB  - Functional magnetic resonance imaging (FMRI) is a new noninvasive technique for
      imaging cerebral function. Studies of the human central auditory pathway examined
      responses in eight normal hearing volunteers following auditory stimuli,
      including narrative speech and pure-tone audiometry. The activation demonstrated
      by FMRI is modeled on an increase in regional blood flow with increased neuronal
      activity. The FMRI signals represent deoxyhemoglobin concentration changes in
      capillaries within the region of the brain that is activated. Brain activation
      was imaged in the superior temporal gyrus during text reading and pure tones.
      Activation in both text and pure-tone presentation did not vary with the
      intensity of the auditory stimulus and elicited a dominant response in the left
      temporal lobe. These observations demonstrate the capability of FMRI to correlate
      anatomic and functional relationships in the human central auditory pathway.

PMID- 8523983
TI  - Fine-needle biopsy techniques of aspiration versus capillary in head and neck
      masses.
AB  - Fine-needle aspiration and fine-needle capillary biopsy techniques were compared,
      and the number of samples necessary to assure a diagnostic specimen was
      determined. In this study, each mass served as its own control, since both
      aspiration and capillary fine-needle biopsy were performed randomly on each mass.
      The study found the number of "superior" slides to be evenly distributed between
      the two biopsy techniques, but a different preference, based on tumor type, was
      noted for one or the other technique. The "best" slides were obtained from one of
      the first four samples 92% of the time. The authors concluded that both fine
      needle aspiration and capillary biopsy should be used and that three to four
      samples should be obtained to increase the likelihood of a diagnostic biopsy.

PMID- 8523984
TI  - Morphologic study of the laryngeal taste buds in the cat.
AB  - The distribution of laryngeal taste buds (TBs) and their neutral components in
      the cat were investigated by immunohistochemistry and electron microscopy. The
      antisera used in this study were against cytokeratin, protein gene product 9.5
      (PGP9.5), neuron-specific enolase (NSE), S-100 protein, calbindin D, calcitonin
      gene-related peptide (CGRP), and substance P (SP). Taste bud cells were
      specifically immunoreactive to the antibodies of human cytokeratin subtypes 8 and
      18 (CAM5.2). On observation with CAM5.2, TBs were seen distributed on the
      laryngeal surface of the epiglottis and spread caudally along the aryepiglottic
      folds, reaching peak density at the laryngeal side of the arytenoid tubercle. The
      PGP9.5 and NSE immunoreactivities were recognized in TB cells and nerve fibers,
      both within the TBs and in the subepithelial connective tissue. S-100 protein
      immunoreactivities were not found in any of the cells in the TBs but were found
      exclusively in the subepithelial neural elements. The calbindin-D, CGRP, and SP
      immunoreactivities were confined to a part of the neural elements that was very
      thin. Taste pores, taste villi, neuronal varicosity, and synapselike structures
      were observed by scanning and transmission electron microscopic study. From these
      results it is considered that the TBs act as a chemical receptor.

PMID- 8523985
TI  - Reducing ischemia-reperfusion injury in rat island groin flaps by dexamethasone
      and BW755C.
AB  - Despite the known effectiveness of anti-inflammatory therapy in reducing
      reperfusion injury, no studies to date involve the use of anti-inflammatory
      therapy in reducing ischemia-reperfusion injury in fasciocutaneous flaps.
      Dexamethasone (a phospholipase A2 inhibitor) and specific cyclooxygenase and
      lipoxygenase inhibitors (indomethacin and BW755C) were administered to rats with
      ischemic island groin (fasciocutaneous) flaps. Significant improvement in
      ischemic flap survival was found with dexamethasone and BW755C. The mode of
      action of dexamethasone was not specifically investigated in our study; however,
      it may suppress neutrophil function and reduce ischemia-reperfusion injury in its
      shared ability with BW755C to reduce the formation of leukotrienes. Dexamethasone
      could be applied in the clinical setting to reduce ischemic flap loss by
      attenuating the systemic inflammatory response to reperfused ischemic-damaged
      tissue.

PMID- 8523986
TI  - Survival of composite chondrocutaneous grafts by vessel implantation: a study in
      the rabbit ear model.
AB  - Composite chondrocutaneous graft reconstruction or reattachment has limited
      applicability, is traditionally restricted to small segmental losses, and is
      dependent on the status of the recipient bed and graft periphery for successful
      revascularization. Surgical enhancement of composite graft survival was
      experimentally investigated in the rabbit ear model through transposition and
      appositional placement of an adjacent vascular pedicle. Fluorescein-derived
      surface-survival determinations, microangiographic vessel-counting methods, and
      histologic analysis were used to study the effects of vascular augmentation,
      pedicle design variations, and angiogenic substance in sixty 8-cm2, full
      thickness auricular grafts. A statistically significant survival advantage was
      demonstrated for the implanted grafts, secondary to perivascular angiogenesis
      from the implanted pedicle.

PMID- 8523987
TI  - Accuracy of intraoperative staging of the NO neck in squamous cell carcinoma.
AB  - Management of the neck in squamous cell carcinoma of the upper aerodigestive
      tract continues to be a topic of great debate. One major problem is that
      incorrect clinical staging is expected in approximately 20% of necks. This is
      true of both clinical stage NO and N+ necks, even when imaging studies are used.
      This prospective study of 108 necks in 79 patients examined the role of
      intraoperative palpation and inspection in improving the surgeon's ability to
      predict nodal stage. Of 62 patients with NO necks clinically on both sides, 26
      were staged N+ by intraoperative node examination. Nineteen of the 26 were
      histologically negative (73% false-positive). Of the 36 patients staged
      intraoperatively as NO, 10 were histologically positive (28% false-negative). Of
      108 necks judged clinically to be NO, 25 (23%) had occult metastases and 11 (10%)
      had extracapsular spread. Forty-one of 108 clinical NO necks were believed to
      have positive nodes at the time of neck dissection. Of these 41 necks, 30 (73%)
      were found to be histologically NO (false-positive). Of the 67 clinical NO necks
      that were also believed to be NO intraoperatively, occult metastases were found
      in 14 (21% false-negative). Therefore, intraoperative staging did not
      significantly improve the false-negative rate. Frozen-section biopsy obtained in
      the operating room was reliable in 24 (92.3%) of 26 patients. Although frozen
      section biopsy was not performed in all patients, these data suggest that
      upstaging the neck without frozen-section biopsy is much less reliable. This
      study supports the use of frozen-section biopsy before converting the selective
      dissection to a radical or modified neck dissection in most instances.

PMID- 8523988
TI  - Suction drain management of salivary fistulas.
AB  - Salivary fistulas remain an unpleasant complication of upper aerodigestive tract
      surgery. To avoid a disastrous outcome such as carotid rupture, clinicians
      "medialize" (i.e., incise the skin flap in the anterior aspect of the neck and
      insert a Penrose drain) to divert fistula fluid from the carotid sheath and then
      perform laborious wound care. Meanwhile, patients endure the unpleasant odor,
      discomfort due to the wound dressing, occasional secondary surgical procedures, a
      lengthened hospital stay, and increased financial costs. In an effort to mitigate
      these problems, suction drains that had been placed at the time of the original
      surgical procedure were used as an alternative management technique. Out of a
      population of 118 reviewable patients who underwent standard or extended
      variations of supraglottic laryngectomy, partial laryngopharyngectomy, near-total
      laryngectomy, or total laryngectomy between 1988 and 1992, 16 patients
      appropriate for inclusion in this study developed postsurgical fistulas. Eight of
      these patients were treated with traditional medialization procedures, and the
      other 8 patients were treated with suction drainage. Comparison of the two groups
      revealed no significant difference with respect to complications or time to
      fistula closure. The advantages of simplified postsurgical care, less patient
      discomfort, reduced time demands on the clinician, and cost containment were
      noted for the group treated with suction drainage.

PMID- 8523989
TI  - Off-axis rotation as a test of otolith function.
AB  - This experiment was performed to determine whether linear acceleration causes a
      change in the vestibulo-linear reflex (VOR) that could be exploited as a research
      and/or clinical test of otolith function. The effect of otolith stimulation on
      the VOR was studied in the horizontal and vertical planes in 10 cats. The VOR was
      induced by pulses of angular acceleration (velocity ramps). During some of the
      test runs, a centripetal linear acceleration stimulus was also applied to
      stimulate the otolith organs. Using the stimuli combination as tested in this
      project, the authors found that otolith stimulation affected the vertical VOR but
      not the horizontal VOR. The vertical VOR was asymmetric. While the methods used
      in this study are useful and the equipment requirements make these techniques
      generally impractical for clinical testing.

PMID- 8523990
TI  - Assessment of serum antibodies in patients with rapidly progressive sensorineural
      hearing loss and Meniere's disease.
AB  - The immunoreactivity of sera from patients with rapidly progressive sensorineural
      hearing loss (SNHL) or Meniere's disease with bovine inner ear material was
      determined using the Western blot technique. Patients with other otologic
      conditions, autoimmune disorders, or arthritic disorders and age-matched randomly
      chosen patients with no hearing complaints served as controls. Twenty-two percent
      of the patients with bilateral rapidly progressive SNHL and 30% of the patients
      with Meniere's disease had antibodies that reacted with a 68 kd antigen in the
      inner ear material. In the control groups, the incidence of reactivity was 5.0%
      (P < .001). When the results of this study were compiled with data collected
      previously, it was found that of 279 patients with bilateral rapidly progressive
      SNHL, 90 (32%) were positive with the 68 kd protein. Thus, the anti-68 kd
      antibody may provide a good marker for an immune etiology of these patients'
      hearing loss.

PMID- 8523991
TI  - Changes in middle ear pressure in daily life.
AB  - The present study was performed to estimate changes of middle ear pressure (ME-P)
      during actions of daily life such as nose blowing and sniffing. ME-P was measured
      in 18 patients with perforation of the eardrum. They were asked to perform
      actions which included nose blowing and sniffing. Eustachian catheterization and
      politzerization were also applied. Change of ME-P before and after these actions
      was recorded using a pressure monitor. Results showed that changes of ME-P after
      nose blowing with both nostrils closed were large and rapid. The mean value of ME
      P after nose blowing was 252 mmH2O. In our previous study, the mean value of
      cerebrospinal fluid pressure (CSF-P) after nose blowing was 388 mmH2O. Therefore,
      the pressure gradient across the cochlear windows is about 130 mmH2O during nose
      blowing. The cochlear windows may have been pressed toward the middle ear side.
      After sniffing, ME-P was unchanged. These results suggest that nose blowing may
      be an important cause of perilymphatic fistula (PLF) via the "explosive route",
      while sniffing is not likely to cause PLF.

PMID- 8523992
TI  - Precision in vocal fold injection: a new technique.

PMID- 8523994
TI  - Directory of otolaryngological societies.

PMID- 8523993
TI  - A safe approach to extensive glottic-level resections prior to epiglottic
      laryngoplasty.

PMID- 8523995
TI  - Successful treatment of herpangina with allopurinol mouthwashes.

PMID- 8523996
TI  - Roadside driver alcohol survey and hospital alcohol survey in Port Moresby, Papua
      New Guinea.
AB  - This article reports the results of a roadside driver alcohol survey undertaken
      jointly by a research team from the Papua New Guinea Department of Transport, the
      Department of Health, the University of Papua New Guinea, the Port Moresby
      General Hospital and the Transport and Road Research Laboratory of the United
      Kingdom.

PMID- 8523997
TI  - Commercial surrogacy and the commodification of children: an ethical perspective.
AB  - The aim of this article is to establish whether there is anything intrinsically
      immoral about surrogacy arrangements from the perspective of the children born
      from such arrangements. We focus on the claim that surrogacy entails the wrongful
      commodification or transfer of children, thereby degrading them and disrespecting
      their inherent moral value as individual human beings.

PMID- 8523998
TI  - Simultaneous strategies to reduce demand for and problematic use of hard drugs.
AB  - The primary responsibility of (local) governments is to enable people to make
      healthy choices in order to promote public health. Social circumstances are
      important determinants of choices that people make. Social risk factors for
      problematic use of drugs should be reduced to a minimum. Health education goals
      need to be matched to the different developmental stages of drug use behaviours
      of subgroups in the population. Employment perspectives for school leavers form
      an essential ingredient of policies which aim to reduce the demand for 'hard'
      drugs in order to divert (young) people from drug careers. Primary preventive
      strategies form the backbone of public policies focused on reduction of demand
      for hard drugs. Primary preventive strategies are population based and
      implemented by the public and private sector. Secondary preventive strategies are
      focused on specific high-risk groups and aim to prevent the development of drug
      dependence and/or to reduce harm for drug users. Tertiary preventive strategies
      are directed at individual hard drug users and emphasize harm reduction and
      rehabilitation of drug users and seek to reduce the side-effects of problematic
      hard drugs use for the general population. Innovative applied research is needed
      to improve field methods for timely detection of problematic hard drug use. More
      information about 'invisible' (hidden) populations of integrated drug users may
      offer new insights and ingredients for preventive policies on hard drugs.

PMID- 8523999
TI  - Marketing of human organs?
AB  - This article discusses the highly controversial question whether human organs
      should be allowed to be the object of a contract aimed at profit. The author
      comes to the conclusion that--seen from a consequentialist viewpoint--the
      legislature is not well-advised to allow organ donations for consideration.
      However, it is admitted that a more deontological approach could come to quite
      the opposite conclusion.

PMID- 8524000
TI  - Agreement between professions on ethical decisions: an empirical demonstration.
AB  - The decisions of a multidisciplinary competency panel at the Baycrest Centre for
      Geriatric Care, Toronto, Canada, were studied to try to explain the high level of
      agreement on individual cases when determining mental capacity. The panel
      assessed its own judgments on a standardized form developed to capture the
      process of coming to a capacity determination. Though the relative weights given
      to decision-making variables varied with discipline, there was agreement on a
      group of criteria most relevant to capacity. Three alternative explanations are
      given for these results.

PMID- 8524001
TI  - Response of the law to developments in genetics.
AB  - In this article, first of all the potential role of the law with regard to
      complex developments like those in genetics is examined; a distinction is made
      between substantive law (for example prohibitions) and procedural law (for
      example licensing systems), and between statutory and voluntary regulation. In
      Europe, in particular the parliament of the European Union has called for
      legislation. Although several European countries have prepared legislation
      relating to particular aspects (for instance embryo research, genetic screening,
      use of genetic tests in employment and insurance), in general the response would
      seem cautious. When legislation is envisaged the outcome of the lawmaking process
      is not always predictable because of moral pluralism and political pressures.
      Legislating in this field is hard also for other reasons, such as the pace of
      development and the difficulty to assess the social consequences of developments.
      Other problems are the similarity or difference between genetic information and
      conventional medical information, and the fact that the developments in genetics
      lay bare more general deficiencies in the social system. With regard to many
      developments, the response of the law in the immediate future should be to
      monitor rather than to ban; where possible, self-regulation should be preferred
      over statutory regulation, and general laws over genetic specific laws. An
      international level, common principles should be adopted to serve as a framework
      for national legislation. Nevertheless, in some areas legislation may already be
      needed: in particular where genetic technologies or their results are being
      applied outside the regular health care setting, for instance in the form of
      population screening or testing for insurance purposes.

PMID- 8524002
TI  - Coronary heart disease complaints against health care personnel in Finland.
AB  - This study comprised all complaints submitted from 1980 to 1990 by coronary
      patients and their relatives to the Finnish National Board of Health (NBH). The
      purpose of this study was to determine the reasons for complaints and their
      consequences. The complaints were coded and the material was analysed using the
      statistical BMDP package. Only 59 of a total of 7,516 complaints dealt with
      coronary disease. The majority of complaints concerned professional technical
      competence. The NBH found negligence in ten cases and gave administrative
      counselling to the professionals at fault. The negligence was not deemed serious
      enough to warrant any penalties or the restriction of licences. Communication
      problems were difficult to prove and none of these complaints resulted in
      counselling. Treatment of coronary heart disease seldom results in a formal
      complaint and negligence is found only in a minority of cases. Patient
      dissatisfaction can well be studied by analysing complaints, but the general
      quality of coronary care has to be addressed with other methods.

PMID- 8524003
TI  - Public and private regulation of reproductive technologies.
AB  - Human reproduction is interrelated with privacy. However, in most countries where
      new reproductive technologies are used public regulations have been passed to
      provide a legal framework for such technologies. This interference in private
      life can be justified by the need to control medical intervention in the human
      reproductive process. But in order to find a balance between public regulations
      and other social regulations, this article analyses the impact private regulation
      may have on issues raised by reproductive technologies. It also addresses the
      issue of the influence of private bodies on the drafting of public regulations.

PMID- 8524004
TI  - The evolution and definition of the concept of 'automatism' in Canadian case law.
AB  - Legal and psychological perspectives are blended in a review of the evolution and
      definition of the legal concept of 'automatism'. Despite the oft-cited, succinct
      definitions such as those provided by Bowlby JA in R v Kasperek [1951] 101 CCC
      375, and by Mr Justice Lacourciere (as he then was) in R v K [1971] 3 CCC (2d) 84
      which emphasize a lack of consciousness, case law has shown a tendency to
      emphasize a lack of volitional control. It has also insisted that such a deficit
      be primarily brought about by an external factor over which the accused either
      had no control or, if they had control, of which effects they lacked knowledge.
      Two noticeable omissions are identified. One is a lack of a logical evaluation of
      expert testimony in terms of the complexity of the criminal acts that have been
      claimed to accompany an impoverished mental state. The other is the failure to
      recognize the mental chemistry of the presence of multiple conditions in the same
      person at the same time. An overriding concern has been protection of the public,
      and decisions in a number of cases can be regarded as attempts to ensure that
      this is achieved before permitting the unqualified acquittal that automatism
      would bring.

PMID- 8524005
TI  - Constitutional aspects of the right to health care in Slovenia.
AB  - Certain aspects of the right to health care and the provision of health insurance
      and health services in Slovenia since its independence and adoption of a
      constitution in December 1991 are discussed. The dilemmas raised by conscientious
      objections by health care workers and the right to legal abortions are
      pertinently dealt with.

PMID- 8524006
TI  - The legal position with regard to informed consent in Denmark.
AB  - Four elements are of importance in the handling of alleged physician faults: the
      political aims in this field, formal rules, administrative practice by the
      disciplinary board, and court rulings. However, in general, the law and the
      guidelines based on it regarding informed consent permit, to a very great extent,
      the physician to determine what relevant information the patient is to receive,
      and violation of the principle of informed consent is judged leniently. It is to
      be questioned whether this satisfies the patient and ensures the right to self
      determination, and whether the regulations or the way in which they are applied
      are in agreement with the political aims in the field. There appears to be a need
      for political and professional debate regarding this issue.

PMID- 8524007
TI  - Revictimization by polygraph: the practice of polygraphing survivors of sexual
      assault.
AB  - Sexual assault survivors are scrutinized in a manner unlike that meted out to any
      other victims of crime. Law enforcement officers or prosecutors may subject the
      survivor to a polygraph exam in an attempt to ascertain the truth or as a
      prerequisite to further investigation of the case. In a survey conducted with
      rape crisis centres across the United States, 63 centres in 17 states reported
      working with survivors of sexual assault who had been polygraphed. Rape crisis
      centres in 11 states reported that children had been polygraphed. This article
      examines the practice of polygraphing survivors of sexual assault.

PMID- 8524008
TI  - The use of ACTH and beta-endorphin levels to measure the stress impact and safety
      of extracorporeal lithotripsy.
AB  - The authors measured the plasma levels of beta-endorphin and adrenocorticotropic
      hormone (ACTH) related to pain in 11 urologic patients who underwent
      extracorporeal lithotripsy. The study included eight male and three female
      patients (aged 24 to 65 years) with single kidney stones of less than 20 mm who
      were treated with the Lithoring Multi-One device. The device delivered 2,000
      shock waves from 18 kV to 25 kV, increasing by 1 kV every 250 shock waves. Three
      patients experienced pain, but only one required intravenous analgesia. The assay
      of plasmatic ACTH and beta-endorphin is proposed to control the safety and the
      stress impact of new devices and techniques. In addition, the study demonstrates
      the medicolegal relevance of such an assay in the evaluation of pain.

PMID- 8524009
TI  - Legal and medical nursing aspects of documentation, recording and reporting.
AB  - This article deals with the importance of documentation, recording and reporting
      as a means of communication in daily medical and nursing practice. It points out
      the common deficiencies in this respect and describes the legal, clinical,
      medical and nursing implications of proper reporting. The medical staff is often
      not sufficiently aware of the importance of accurate reporting. The inadequate
      compiling and incorrect reading of medical records can jeopardize patients'
      rights to quality service.

PMID- 8524010
TI  - Sexual abuse experiences of psychiatric patients.
AB  - By interviewing 200 male psychiatric patients and 150 female psychiatric
      patients, we found that 17.1% of the respondents had experienced sexual
      victimization during their childhood. Only 11% of a control group of 50 males and
      50 females, who had never received psychiatric treatment, reported similar
      victimization. The incidence of intrafamilial sexual victimization was greater
      among females than males. The group that had suffered the most sexual
      victimization was that of female psychiatric patients diagnosed with neuroses.
      Sexual victimization linked to aggressive behaviour and threats of violence was
      more common in the case of male and female psychiatric patients than in the
      control groups. Only 4% of the sexual victimization cases were investigated by
      the police.

PMID- 8524011
TI  - Aggressive behaviour as a cause of psychiatric admission: a comparison between
      schizophrenic and affective disorder patients.
AB  - One hundred and fifty-six subjects were randomly chosen from 1,560 patients
      admitted to two psychiatric hospitals in Israel during 1991. The subjects' files
      were retrospectively studied to determine whether aggressive behaviour was the
      reason for psychiatric admission. We examined the relationship between aggressive
      behaviour, major psychiatric disorders (schizophrenia and affective disorder) and
      demographic variables (sex, age, family status and education). We also studied
      the monthly distribution of aggression throughout the year and the correlation to
      daily photoperiod duration. Forty-six per cent of the admissions related to
      aggressive behaviour. Schizophrenic patients were overly represented in the
      aggressive group. The monthly distribution of aggressive behaviour differed
      between schizophrenic and affective disorder patients. While the latter showed a
      seasonal pattern of aggressiveness, with a statistically significant peak during
      spring and winter, schizophrenic aggressive patients were distributed equally
      throughout the year. No statistically significant correlation was found between
      the incidence of aggression and the photoperiod duration.

PMID- 8524012
TI  - An integrative model for the delivery of mental health services for minors--the
      role of psychiatric hospitalization.
AB  - The recent increase in psychiatric hospitalization of minors is reviewed. The
      Israeli mental health legislation is described and the lack of adequate
      coordination between agencies delivering mental health services for minors is
      noted. Two case vignettes are described which demonstrate the management problem
      posed by severely emotionally disturbed minors at risk who are not adequately
      catered for by the current Youth Protection Law or the mental health legislation.
      An integrative model for the delivery of mental health services for minors is
      proposed demonstrating the need for close collaboration between psychiatric and
      statutory welfare services and the role of psychiatric hospitalization.

PMID- 8524013
TI  - New subordinate psychiatric legislation in Israel.
AB  - The 1991 Mental Health Act left considerable scope for the promulgation of
      regulations, which were indeed enacted a year later, in 1992. The 1992
      regulations are analysed here. The innovations and improvements introduced, as
      well as the problems and difficulties created by the regulations are discussed.
      It is vital to review and revise psychiatric legislation constantly.

PMID- 8524014
TI  - Two methods of authenticating past criminal conduct by psychiatric inpatients: a
      comparison of clinical chart reports and criminal records.
AB  - Clinical chart reports on criminal activity based primarily on the patients' own
      reports were compared with official criminal records of their convictions in a
      large group of male inpatients suffering from schizophrenia, affective disorder
      and alcoholism. In 69% of the cases studied there was uniformity between both
      methods of ascertaining criminal activity. A considerable proportion (26%) of
      schizophrenic patients' clinical charts indicated criminal behaviour which was
      not officially registered in criminal records, whereas a substantial proportion
      (24%) of alcoholics did not report their criminal activities in their clinical
      records in spite of these being recorded in their criminal records. The
      conclusion is that official criminal records provide an incomplete account of
      infractions of the law by psychiatric, especially schizophrenic patients. The
      information recorded in official records seems to be less accurate than that in
      clinical charts in the case of schizophrenics, but more veracious in the case of
      alcoholics. When investigating the frequency of criminal behaviour by psychiatric
      patients these findings will therefore have to be taken into consideration.

PMID- 8524015
TI  - Particles and analysis.

PMID- 8524016
TI  - 1H MRS of human brain abscesses in vivo and in vitro.
AB  - Five patients, each with a brain abscess, were examined by means of 1H MR
      spectroscopic imaging in vivo. The aspirated pus was analyzed in vitro by means
      of 1D and 2D COSY 1H MRS. In addition to resonance lines from compounds (lactate,
      alanine and lipids) often found in the spectra from intracranial tumors,
      resonance lines were detected from a number of markers of infectious involvement
      (acetate, succinate, and various amino acids). These results suggest that 1H MRS
      in vivo might contribute in establishing noninvasively a differential diagnosis
      between brain abscess and tumor.

PMID- 8524017
TI  - The apparent diffusion constant measured by MRI correlates with pO2 in a RIF-1
      tumor.
AB  - As tissue oxygen tension (pO2) is an important variable in cancer therapy, it
      would be of major clinical benefit to be able to measure pO2 noninvasively.
      Current methods for determining pO2 in clinical settings are limited to
      superficial tumors. The authors measured the apparent diffusion constant (ADC) in
      an implanted murine fibrosarcoma (RIF-1) using magnetic resonance imaging and
      correlated the ADC with tissue pO2 measured by electron paramagnetic resonance
      oximetry. The ADC correlates significantly with tissue pO2 in this tumor (r =
      0.89; n = 14) and so may provide a noninvasive index of pO2 in tumors.

PMID- 8524018
TI  - Interleaved asymmetric echo-planar imaging.
AB  - A version of interleaved echo-planar imaging (EPI) is presented in which only one
      polarity of the readout gradient is used for signal acquisition to avoid ghosting
      artifacts. Two possible forms of the phase encoding gradient, blipped and
      constant, are discussed. With the constant phase encoding, interleaving of
      partial trajectories in the Fourier domain (k-space) is controlled automatically
      by the echo train delay. The constant phase encoding gradient introduces a shear
      distortion of the k-space grid. A modification of the reconstruction procedure is
      given which corrects for this effect. The method provides a 128 x 128 image in 1
      s on a clinical system with standard gradients.

PMID- 8524019
TI  - Ultra-fast imaging using low flip angles and FIDs.
AB  - A new ultra-fast imaging technique that does not place extreme demands on the
      speed of the gradient system is described. When used with comparable MRI systems,
      the rotating ultra-fast imaging sequence (RUFIS) can acquire images 4 to 5 times
      faster than gradient-moment nulled EPI and more than twice as fast as DUFIS,
      OUFIS, or BURST techniques. Because the technique uses free induction decays
      instead of echoes, it can be made particularly insensitive to effects of motion,
      flow, and diffusion. Preliminary images of turbulent flow are presented to
      demonstrate this insensitivity. However, with appropriate encoding, flow effects
      may be imaged.

PMID- 8524020
TI  - Fast anatomical imaging of the heart and assessment of myocardial perfusion with
      arrhythmia insensitive magnetization preparation.
AB  - A new contrast preparation based on modified driven equilibrium Fourier transfer
      is introduced and evaluated for generation of T1-weighted images for assessment
      of the myocardial perfusion with contrast agent first-pass kinetics. The new
      preparation scheme produces T1 contrast with insensitivity to arrhythmias in
      prospectively triggered sequential imaging thereby eliminating one of the major
      sources of problems in potential patient studies with previously employed
      contrast preparations schemes.

PMID- 8524021
TI  - Functional connectivity in the motor cortex of resting human brain using echo
      planar MRI.
AB  - An MRI time course of 512 echo-planar images (EPI) in resting human brain
      obtained every 250 ms reveals fluctuations in signal intensity in each pixel that
      have a physiologic origin. Regions of the sensorimotor cortex that were activated
      secondary to hand movement were identified using functional MRI methodology
      (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain
      were observed to have a high degree of temporal correlation (P < 10(-3)) within
      these regions and also with time courses in several other regions that can be
      associated with motor function. It is concluded that correlation of low frequency
      fluctuations, which may arise from fluctuations in blood oxygenation or flow, is
      a manifestation of functional connectivity of the brain.

PMID- 8524022
TI  - In vivo 31P spectroscopy study of treated and untreated recovery of rat partial
      brain ischemia.
AB  - Quantitative 31P NMR was used to follow the time variation of the hypometabolic
      response to hypoxic partial ischemia in an animal model. The purpose of the study
      was to establish the value of this repeated spectroscopy operating by means of a
      surface coil. It aimed at determining whether a therapeutic intervention could
      influence the transient changes occurring during the insult or early recovery. A
      pharmacological substance was thus used during a reversible forebrain ischemia,
      induced by a combination of vascular occlusion and mild hypoxia in two groups of
      rats. As an available and convenient example, L-carnitine was chosen. Statistical
      analysis of the experimental results revealed a significant difference of the Pi
      and PCr levels between treated and untreated animals.

PMID- 8524023
TI  - High resolution solid-state 29Si NMR spectroscopy of silicone gels used to fill
      breast prostheses.
AB  - We have used 29Si solid-state nuclear magnetic resonance (NMR) spectroscopy to
      study the chemical structure of the silicone gels in virgin and explanted breast
      prostheses. Despite evidences of alteration in the morphological appearance of
      the silicone gel inside the breast prosthesis, our results do not reveal changes
      in the chemical nature and structure of the silicone gels after implantation. In
      addition to the main 29Si resonance peak at -22.26 ppm that corresponds to the
      resonance frequency of the D repeat unit of the polysiloxane chains, the high
      sensitivity of our NMR technique allows the detection of very low concentrations
      of silicone compounds. Within our experimental detection limit of 0.2%, no signal
      between -90 ppm and -150 ppm are observed. This indicates that no silica products
      are present inside the gel of the prostheses. Furthermore, our 29Si NMR spectra
      indicate differences in the chemical compositions of the silicone gels from
      different manufacturers.

PMID- 8524024
TI  - MR contrast due to intravascular magnetic susceptibility perturbations.
AB  - A particularly powerful paradigm for functional MR imaging of microvascular
      hemodynamics incorporates paramagnetic materials that create significant image
      contrast. These include exogenous (lanthanide chelates) and endogenous
      (deoxygenated hemoglobin) agents for mapping cerebral blood volume and neuronal
      activity, respectively. Accurate interpretation of these maps requires an
      understanding of the biophysics of susceptibility-based image contrast. The
      authors developed a novel Monte Carlo model with which the authors quantified the
      relationship between microscopic tissue parameters, NMR imaging parameters, and
      susceptibility contrast in vivo. The authors found vascular permeability to water
      and the flow of erythrocytes to be relatively unimportant contributors to
      susceptibility-induced delta R2. However, pulse sequence, echo time, and
      concentration of contrast agent have profound effects on the vessel size
      dependence of delta R2. For a model vasculature containing both capillaries and
      venules, the authors predicted a linear volume fraction dependence for
      physiological volume changes based on recruitment and dilation, and a
      concentration dependence that is nonlinear and pulse sequence dependent. Using
      the model, the authors demonstrated that spin echo functional images have greater
      microvascular sensitivity than gradient echo images, and that the specifies of
      the volume fraction and concentration dependence of transverse relaxivity change
      should allow for robust mapping of relative blood volume. The authors also
      demonstrated excellent agreement between the predictions of their model and
      experimental data obtained from the serial injection of superparamagnetic
      contrast agent in a rat model.

PMID- 8524025
TI  - Simultaneous calculation of flow and diffusion sensitivity in steady-state free
      precession imaging.
AB  - In this paper the authors quantitatively evaluate the combined effect of both
      flow and diffusion in steady-state free precession (SSFP) imaging. A partition
      analysis (PA) is used to derive a fourth order approximation (in E2) of the
      signal in an echo SSFP sequence. The authors also introduce a novel very fast
      simulation technique, based on a circular convolution, which accurately accounts
      for both flow and diffusion. A 2D SSFP-echo sequence was implemented to obtain
      experimental data from a phantom containing three different solutions. Excellent
      agreement between the theory and the experimental data was found. Then by using
      the simulation algorithm and experimental measurements of in vivo brain motion,
      the authors estimated the artifacts to be expected in SSFP diffusion imaging of
      the brain and found them to be comparable with those of pulsed gradient spin
      echo. Finally, the authors point out the equivalence between the flow sensitivity
      of SSFP and RF spoiling commonly used in fast imaging.

PMID- 8524026
TI  - Spiral imaging on a small-bore system at 4.7T.
AB  - Spiral imaging has a number of advantages for ultrafast data acquisition.
      However, implementation on high-field small-bore systems requires carefully
      addressing the issues of inhomogeneity-induced blurring and gradient hardware
      constraints. In this paper, spiral imaging on a 40-cm-bore 4.7T CSI Omega System
      (Bruker Instruments) is discussed. A constant-voltage gradient waveform design
      algorithm is developed to reduce readout times as well as minimize waveform
      distortions due to gradient amplifier nonlinearities. Residual errors are then
      measured and taken into account in the image reconstruction procedure. Multiple
      spiral interleaves as well as a multifrequency reconstruction algorithm are used
      to decrease blurring of off-resonance spins. Both phantom and in vivo images
      demonstrate the performance of the resulting pulse sequences.

PMID- 8524027
TI  - High resolution renal diffusion imaging using a modified steady-state free
      precession sequence.
AB  - A modified steady-state free precession (SSFP) diffusion sequence is proposed for
      high resolution renal imaging. A pair of bipolar diffusion gradients was used to
      minimize the errors in measured apparent diffusion coefficient (ADC) caused by
      variations in T1, T2, and RF flip angle that have been observed with previously
      employed SSFP diffusion sequences. Motion sensitivity was reduced by the use of
      compensated gradients, frame-by-frame averaging, and a repetition time of 22 ms,
      which for a single-acquisition 128 x 128 image requires only 3 s. High resolution
      was achieved by signal averaging. The modified sequence was applied to in vivo
      diffusion measurements. In six normal rat kidneys the ADCs (mean +/- SD; x 10(-3)
      mm2/s) of the cortex, outer medulla, and inner medulla were 2.28 +/- 0.05, 2.38
      +/- 0.10, and 2.95 +/- 0.05, respectively. The technique requires relatively
      large gradients to achieve adequate diffusion weighting.

PMID- 8524028
TI  - Quantitative NMR microscopy of multicellular tumor spheroids and confrontation
      cultures.
AB  - In cancer research, tumor spheroids are a well established system to study tumor
      metabolism resembling the situation in vivo more closely cell monolayers.
      Spherical aggregates of malignant melanoma cells (MV3) and their invasion into
      rat brain aggregates have been investigated by quantitative NMR microscopy.
      Relaxation times (T1, T2) and diffusion parameter images were acquired with an in
      plane resolution of 14 x 14 microns2. The authors were able to demonstrate that
      the morphology of the spheroids can be visualized on these NMR maps. The contrast
      was mainly manifested in relaxation maps, where average relaxation times T1 =
      1.94 +/- 0.17 s and T2 = 42.8 +/- 6.3 ms were obtained for proliferating cells,
      and T1 = 2.49 +/- 0.31 s and T2 = 104.3 +/- 29.4 ms for the necrobiotic center.
      The mean diffusion coefficients were 0.59 +/- 0.12 micron2/ms and 0.85 +/- 0.14
      micron2/ms, respectively. The authors could follow the dynamic process of tumor
      cell invasion in the investigated co-culture system. Knowledge about tumor cell
      migration and tumor cell invasion is essential for the understanding of cancer
      and its therapy. Quantitative NMR microscopy can study this dynamic process
      noninvasively and therefore may help to assess the influence of therapy on the
      micromilieu of these spheroids.

PMID- 8524029
TI  - A novel transverse gradient coil design for high-resolution MR imaging.
AB  - The authors describe a new gradient coil design for high resolution human,
      animal, specimen, or phantom imaging with high gradient efficiency and a large
      region of excellent gradient uniformity. Important features of our new design are
      the simple analytical description of the wire patterns that comprise the design,
      and ease of construction. Wires are spaced in a sinusoidal distribution around
      the circumference of the cylinder, and curved in an arcsin shape along the length
      of the cylinder. This coil produces a magnetic field pointing in a direction
      transverse to the axis of the coil with a gradient in the direction parallel to
      the axis of the coil. The same arcsin coil can be used to create a magnetic field
      pointing in a direction parallel to its axis with a gradient in a direction
      perpendicular to the coil axis. A prototype coil was constructed; field and
      inductance calculations were verified. Geometric variations on this coil design
      were modeled and their performance characteristics compared. This coil design is
      ideal for rapid implementation of a transverse gradient coil, since no
      specialized design software is required.

PMID- 8524030
TI  - A computer simulation program for MR imaging: application to RF and static
      magnetic field imperfections.
AB  - A computer simulation program capable of demonstrating various artifacts, such as
      image distortion caused by metallic implants in MR imaging, is presented. The
      structure of the program allows for the implementation of various imaging
      situations as long as spins only experience weak interaction, i.e., the Bloch
      equations are obeyed. The raw data are obtained by repeatedly applying the Bloch
      equations to the magnetization vector of each point of the simulated object,
      throughout the pulse sequence. With only a limited number of spins in each voxel,
      the effects of intravoxel dephasing and rephasing require special attention, and
      algorithms for this have been implemented.

PMID- 8524031
TI  - A time encoding method for single-shot imaging.
AB  - A new 2D single-shot imaging technique is introduced that uses only one dimension
      of Fourier encoding. The second dimension is encoded in time, rather than using
      phase encoding. The data is acquired in the form of a closely spaced echo train
      with each echo produced from a different physical line in the object. A 1D
      Fourier transform is applied to each echo for image reconstruction. Because only
      the desired lines are excited, there can be no aliasing in the time encoding
      direction even when the object is much larger than the field of view. This
      technique is also very insensitive to motion, as motion-related artifacts do not
      propagate in the time encoding direction.

PMID- 8524032
TI  - Blood oxygenation dependence of T1 and T2 in the isolated, perfused rabbit heart
      at 4.7T.
AB  - An MR line scan protocol has been used to measure relaxation parameters (T1 and
      T2) in isolated, blood perfused rabbit hearts at various blood oxygenations.
      Hearts were retrogradely perfused at 37 degrees C with a cardioplegic solution
      (modified St. Thomas' solution) containing sheep red blood cells and adenosine (1
      mM) to maximally vasodilate the coronary vascular bed. Arresting the hearts
      eliminated motion complications and minimized arteriovenous oxygenation
      differences. The authors have found that under conditions of stable flow, there
      is a strong correlation between T2 in myocardial septa and hemoglobin (Hb)
      saturation, while tissue T1 is virtually independent of blood oxygenation. These
      effects are believed to be due to the paramagnetic agent deoxyhemoglobin.

PMID- 8524033
TI  - Validation of 19F-magnetic resonance determination of myocardial blood volume.
AB  - The use of perfluorochemical (PFC) emulsions to study the myocardial circulation
      by means of 19F NMR requires that the biodistribution of the PFC be known. The
      authors tested the hypothesis that PFC particles remain within the myocardial
      vascular space by infusing rats with both a PFC emulsion and 125I-albumin.
      Measurement of myocardial vascular volume by 19F NMR and by standard radiotracer
      analysis of the same tissue yielded concordant values by the two methods,
      establishing the PFC emulsion as an intravascular agent in this tissue.
      Perfluorochemical emulsions should be useful for the noninvasive study of
      myocardial vascular physiology by magnetic resonance.

PMID- 8524034
TI  - Reduction of phase error ghosting artifacts in thin slice fast spin-echo imaging.
AB  - Fast spin-echo (FSE) imaging techniques are very sensitive to the relative phase
      between the 90 degrees (excitation) RF pulse and the 180 degrees (refocusing) RF
      pulses. In this paper, it is demonstrated that a phase shift can be created
      between the excitation and refocusing pulses in such a manner that the received
      signal is divided into two components of distinctly different phase shifts. The
      nature of these two components is reviewed. It is demonstrated that ghosting
      artifacts will occur when images are reconstructed from this received signal. The
      ghosting is shown to be object dependent. A correction technique is presented
      which calculates the phase errors among different echoes based on measurements
      from a single echo train acquired without phase encoding gradients. The results
      in both phantom and human studies show that this method is capable of reducing
      the ghosting artifact in thin slice FSE images.

PMID- 8524035
TI  - Functional MRI of human brain activation combining high spatial and temporal
      resolution by a CINE FLASH technique.
AB  - Functional mapping of human brain activation has been accomplished at high
      spatial and temporal resolution (voxel size 4.9 microliter, temporal increment
      100 ms). The approach was based on oxygenation-sensitive long-echo time FLASH MRI
      sequences synchronized to multiply repeated cycles of visual stimulation in a
      CINE acquisition mode. This high temporal resolution revealed that stimulus
      related signal intensity changes in human visual cortex display an initial
      latency followed by increases extending over several seconds. Furthermore, the
      temporal characteristics of the complete CINE MRI signal time course depended on
      the absolute and relative durations of activation and control periods and, for
      example, caused an apparent absence of a poststimulation "under-shoot"
      phenomenon. Complementing hyperoxygenation due to rapid hemodynamic adjustments,
      these results suggest signal intensity modulation by enhanced oxygen consumption
      and concomitant deoxygenation during prolonged and/or repetitive stimulation.

PMID- 8524036
TI  - Evolutionary dynamics of the enhancer region of even-skipped in Drosophila.
AB  - We report findings on naturally occurring variation in the regulatory region of
      even-skipped in Drosophila. This pair-rule gene encodes a homeobox-containing
      transcription factor, is expressed as a series of seven transverse stripes in
      developing embryos, and defines parasegmental boundaries. The 5' flanking region
      of the gene contains a 671-bp enhancer governing stripe 2 expression. The stripe
      2 enhancer contains multiple binding sites for four transcription factors that
      provide positional information in developing blastoderm, the positive regulators
      bicoid and hunchback and the repressors giant and Kruppel. The study compares
      polymorphism and divergence in Drosophila melanogaster and Drosophila simulans
      for the enhancer region, the spacer between the enhancer and the transcription
      start site, the untranslated leader, the first exon and the intron of eve.
      Contrary to expectations, we find a relatively high level of variation in the
      stripe 2 enhancer region, including point substitutions and insertion/deletions
      in binding sites, and a comparable level of variation in the other noncoding
      regions. The patterns of variation and divergence within the enhancer region and
      between regions of the locus fit a model of neutral molecular evolution. We
      suggest that the multiplicity of binding sites in the enhancer provides a
      redundancy in function that allows flexibility in the sequence requirements and
      structural design of the promoter.

PMID- 8524037
TI  - Arbitrarily primed DNA fingerprinting for phylogenetic reconstruction in
      vertebrates: the Xiphophorus model.
AB  - Arbitrarily primed PCR (AP-PCR or RAPD) is a technique for producing species
      specific DNA fingerprints. We tested the utility of AP-PCR as a source of
      phylogenetically informative characters in three separate experiments, using
      fishes of the genus Xiphophorus. We chose Xiphophorus as a standard of
      comparison, because evolutionary relationships within the genus have been studied
      repeatedly using a variety of techniques. We compared our results to a
      "classical" phylogenetic hypothesis synthesized from studies using morphological,
      pigmentation, and allozyme characters, and to a recent conflicting hypothesis
      constructed from DNA sequence data. The sequence-based hypothesis places the
      southern swordtail Xiphophorus clemenciae squarely within the platyfish, whereas
      the classical hypothesis separates the two groups. In addition, the two
      hypotheses differ in their clustering of species of northern swordtails. Our
      findings are in close accord with the classical hypothesis. Our results allow the
      strongest phylogenetic hypothesis yet for Xiphophorus and demonstrate the utility
      of AP-PCR for studying species relationships within vertebrate genera.

PMID- 8524038
TI  - Phylogenetic analysis of cichlid fishes using nuclear DNA markers.
AB  - The recent explosive adaptive radiation of cichlids in the great lakes of Africa
      has attracted the attention of both morphologists and molecular biologists. To
      decipher the phylogenetic relationships among the various taxa within the family
      Cichlidae is a prerequisite for answering some fundamental questions about the
      nature of the speciation process. In the present study, we used the random
      amplification of polymorphic DNA (RAPD) technique to obtain sequence differences
      between selected cichlid species. We then designed specific primers based on
      these sequences and used them to amplify template DNA from a large number of
      species by the polymerase chain reaction (PCR). We sequenced the amplified
      products and searched the sequences for indels and shared substitutions. We
      identified a number of such characters at three loci--DXTU1, DXTU2, and DXTU3-
      and used them for phylogenetic and cladistic analysis of the relationships among
      the various cichlid groups. Our studies assign an outgroup position to
      Neotropical cichlids in relation to African cichlids, provide evidence for a
      sister-group relationship of tilapiines to the haplochromines, group Cyphotilapia
      frontosa with the lamprologines of Lake Tanganyika, place Astatoreochromis
      alluaudi to an outgroup position with respect to other haplochromines of Lakes
      Victoria and Malawi, and provide additional support for the monophyly of the
      remaining Lake Victoria haplochromines and the Lake Malawi haplochromines. The
      described approach holds great promise for further resolution of cichlid
      phylogeny.

PMID- 8524039
TI  - Variation in heat shock proteins within tropical and desert species of poeciliid
      fishes.
AB  - The 70-kilodalton heat shock protein (hsp70) family of molecular chaperones,
      which contains both stress-inducible and normally abundant constitutive members,
      is highly conserved across distantly related taxa. Analysis of this protein
      family in individuals from an outbred population of tropical topminnows,
      Poeciliopsis gracilis, showed that while constitutive hsp70 family members showed
      no variation in protein isoforms, inducibly synthesized hsp70 was polymorphic.
      Several species of Poeciliopsis adapted to desert environments exhibited lower
      levels of inducible hsp70 polymorphism than the tropical species, but
      constitutive forms were identical to those in P. gracilis, as they were in the
      confamilial species Gambusia affinis. These differences suggest that inducible
      and constitutive members of this family are under different evolutionary
      constraints and may indicate differences in their function within the cell. Also,
      northern desert species of Poeciliopsis synthesize a subset of the inducible
      hsp70 isoforms seen in tropical species. This distribution supports the theory
      that ancestral tropical fish migrated northward and colonized desert streams; the
      subsequent decrease in variation of inducible hsp70 may have been due to genetic
      drift or a consequence of adaptation to the desert environment. Higher levels of
      variability were found when the 30-kilodalton heat shock protein (hsp30) family
      was analyzed within different strains of two desert species of Poeciliopsis and
      also in wild-caught individuals of Gambusia affinis. In both cases the
      distribution of hsp30 isoform diversity was similar to that seen previously with
      allozyme polymorphisms.

PMID- 8524040
TI  - Phylogenetic analysis of the 90 kD heat shock family of protein sequences and an
      examination of the relationship among animals, plants, and fungi species.
AB  - The heat shock protein (Hsp) sequences, because of their ubiquity and high degree
      of conservation, provide useful models for phylogenetic analysis. In this paper I
      have carried out a global alignment of all available sequences (a total of 31)
      for the 90-kD heat shock protein (Hsp90) family. The minimum amino acid identity
      that is seen between presently known Hsp90 homologs is about 40% over the entire
      length, indicating that it is a highly conserved protein. Based on the alignment,
      a number of signature sequences that either are distinctive of the Hsp90 family
      or that distinguish between the cytosolic and the endoplasmic reticular forms of
      Hsp90 have been identified. Detailed phylogenetic analyses based on Hsp90
      sequences reported here strongly indicate that the cytosolic and the endoplasmic
      reticulum (ER) resident forms of Hsp90 constitute paralogous gene families which
      arose by a gene duplication event that took place very early in the evolution of
      eukaryotic cells. A minimum of two additional gene duplication events, which took
      place at a later time, are required to explain the presence of two different
      forms of Hsp90 that are found in fungi and vertebrate species. In a consensus
      neighbor-joining bootstrap tree based on Hsp90 sequences, plants and animals
      species grouped together 989 times of 1,000 (a highly significant score),
      indicating a closer relationship between them as compared to fungi. A closer
      affiliation of plant and animal species was also observed in the maximum
      parsimony tree, although the relationship was not significantly supported by this
      method. A survey of the recent literature on this subject indicates that
      depending on the protein sequence and the methods of phylogenetic analysis, the
      animal species are indicated as closer relatives to either plants or fungi with
      significant statistical support for both topologies. Thus the relationship among
      the animal, plant, and fungi kingdoms remains an unresolved issue at the present
      time.

PMID- 8524041
TI  - Size homoplasy and mutational processes of interrupted microsatellites in two bee
      species, Apis mellifera and Bombus terrestris (Apidae).
AB  - Similar microsatellite electromorphs (PCR products of the same size) can arise
      from independent mutational events. Such alleles are not identical by descent.
      This phenomenon, termed size homoplasy, was studied by sequencing electromorphs
      of two microsatellite loci in which the stretch of basic repeats is interrupted
      by different short (1-2 bp) DNA motifs. The number and position of these
      interruptions were established for electromorphs from closely and distantly
      related populations of honeybees and bumblebees. No sequence difference was found
      when electromorphs came from the same subspecies or from closely related
      subspecies, suggesting that they were probably identical by descent. In contrast,
      sequence differences were often detected in distantly related subspecies, showing
      that size homoplasy frequently occurs at this level of population
      differentiation. Size homoplasy is increased by limits to free length variation
      of alleles, a phenomenon that seems to act on interrupted microsatellites when
      comparing distantly related taxa, that is, honeybee subspecies from different
      evolutionary lineages. Electromorph sequences suggest that, within the scope of
      these limits, large mutation events have occurred frequently at both interrupted
      loci studied. In good agreement with the molecular data, computations based on
      the observed heterozygosity and number of electromorphs and simulation studies
      showed that neither locus fits the one-step stepwise mutant model (SMM). We
      speculate that interrupted microsatellites in general could be characterized by a
      higher variance in repeat number and consequently a lower homoplasy rate than
      pure ones. Hence, interrupted microsatellites should be most appropriate for
      investigating population differentiation and evolutionary relationship between
      relatively distant populations.

PMID- 8524042
TI  - Evolutionary stability of the R1 retrotransposable element in the genus
      Drosophila.
AB  - R1 is a non-long terminal repeat (non-LTR) retrotransposable element that inserts
      into a specific sequence of insect 28S ribosomal RNA genes. We have previously
      shown that this element has been maintained through vertical transmission in the
      melanogaster species subgroup of Drosophila. To address whether R1 elements have
      been vertically transmitted for longer periods of evolutionary time, the analysis
      has been extended to 11 other species from four species groups of the genus
      Drosophila (melanogaster, obscura, testecea, and repleta). All sequenced elements
      appeared functional on the basis of the preservation of their open-reading frames
      and consistently higher rate of substitution at synonymous sites relative to
      replacement sites. The phylogenetic relationships of the R1 elements from all
      species analyzed were congruent with the species phylogenies, suggesting that the
      R1 elements have been vertically transmitted since the inception of the
      Drosophila genus, an estimated 50-70 Mya. The stable maintenance of R1 through
      the germ line appears to be the major mechanism for the widespread distribution
      of these elements in Drosophila. In two species, D. neotestecea of the testecea
      group and D. takahashii of the melanogaster group, a second family of R1 elements
      was also present that differed in sequence by 46% and 31%, respectively, from the
      family that was congruent with the species phylogeny. These second families may
      represent occasional horizontal transfers or, alternatively, they could reflect
      the ability of R1 elements to diverge into new families within a species and
      evolve independently.

PMID- 8524043
TI  - Microsatellite evolution in congeneric mammals: domestic and bighorn sheep.
AB  - We compared genotypes at eight (AC)n microsatellite loci in domestic sheep (Ovis
      aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The domestic sheep
      had greater genetic variation, higher allele-size variances, and larger allele
      sizes than the wild sheep. Accumulating evidence from higher taxonomic
      comparisons shows that these parameters are biased if microsatellite loci are
      selected in one taxon and used in another. Our results demonstrate similar biases
      between congeneric species. We compared standard measures of genetic variation,
      differentiation, and distance within and between species (H, D, FST) to newer
      measures based on allele-size variance (SW, SB, RST). The size-based distances
      better detected species-level divergence, but standard measures better
      distinguished allopatric populations. Empirical calibration of these measures at
      the subspecies level is needed to establish their useful ranges.

PMID- 8524044
TI  - Mitochondrial DNA sequence evolution in sharks: rates, patterns, and phylogenetic
      inferences.
AB  - Abundant representation of sharks in the fossil record makes this group a superb
      system in which to investigate rates and patterns of molecular evolution and to
      explore the strengths and weaknesses of phylogenetic inferences from molecular
      data. In this report, the molecular evolution of the cytochrome b gene in sharks
      is described and the information related to results from phylogenetic analysis of
      the data evaluated in the light of a phylogeny derived independently of the
      molecular data. Across divergent lineages of sharks there is evidence for
      significant substitution rate variation, departure from compositional
      equilibrium, and substantial homoplasy; nevertheless, the signal of evolutionary
      history is evident in patterns of shared transversions and amino acid
      replacements.

PMID- 8524045
TI  - Metabolic rate and directional nucleotide substitution in animal mitochondrial
      DNA.
AB  - There is marked heterogeneity of nucleotide composition in mitochondrial DNA
      across divergent animals. Differences in nucleotide composition presumably
      reflect differences in directional nucleotide substitution for A+T or G+C
      nucleotides. In mitochondrial DNA, there is A+T directional nucleotide
      substitution in most (if not all) animals surveyed, and the magnitude of
      directional A+T nucleotide substitution differs greatly within and among groups.
      Differences in directional nucleotide substitution among lineages of mammals can
      be explained by changes in metabolic physiology. This relationship is thought to
      be mediated by the effect of oxygen radicals because these toxic compounds are by
      products of aerobic metabolism and are known mutagens. Association between
      metabolism and nucleotide composition provides additional evidence in favor of
      the hypothesis that rates and patterns of nucleotide substitution in
      mitochondrial DNA can be influenced by factors that impinge on rates of
      endogenous DNA damage.

PMID- 8524046
TI  - 18S rRNA data indicate that Aschelminthes are polyphyletic in origin and consist
      of at least three distinct clades.
AB  - The Aschelminthes is a collection of at least eight animal phyla, historically
      grouped together because the absence of a true body cavity was perceived as a
      pseudocoelom. Analyses of 18S rRNA sequences from six Aschelminth phyla
      (including four previously unpublished sequences) support polyphyly for the
      Aschelminthes. At least three distinct groups of Aschelminthes were detected: the
      Priapulida among the protostomes, the Rotifera-Acanthocephala as a sister group
      to the protostomes, and the Nematoda as a basal group to the triploblastic
      Eumetazoa.

PMID- 8524047
TI  - Compensatory substitutions and the evolution of the mitochondrial 12S rRNA gene
      in mammals.
AB  - 12S ribosomal RNA (rRNA) gene sequences from a suite of mammalian taxa (13
      placentals, 4 marsupials, 1 monotreme), for which phylogenetic relationships are
      well established based on independent criteria, were employed to study the
      evolution of this gene. Phylogenetic analysis of 12S sequences produces a
      phylogeny that agrees with expectations. Base composition provides evidence for
      directional symmetrical substitution pressure in loops; in stems, base
      composition is much more even. Rates of nucleotide substitution are lower in
      stems than loops. Patterns of nucleotide substitution show an overall preference
      for transitions over transversions, with this difference more profound in stems
      than loops. Among different transversion pathways, there is a wide range of
      transformation frequencies. An analysis of compensatory substitutions shows that
      there is strong evidence for their occurrence and that a weighting factor of 0.61
      should be applied in phylogenetic analyses to account for the dependence of
      mutations at stem positions relative to positions where changes are independent.
      Among stem variables (i.e., stem length, interaction distance, substitution
      rates, G+C content, and the percentage of bases that are paired), several
      significant correlations were discovered, but stem length and interaction
      distance are uncorrelated with other variables.

PMID- 8524048
TI  - An early origin of plastids within the cyanobacterial divergence is suggested by
      evolutionary trees based on complete 16S rRNA sequences.
AB  - It is generally accepted that the plastids arose from a cyanobacterial ancestor,
      but the exact phylogenetic relationships between cyanobacteria and plastids are
      still controversial. Most studies based on partial 16S rRNA sequences suggested a
      relatively late origin of plastids within the cyanobacterial divergence. In order
      to clarify the exact relationship and divergence order of cyanobacteria and
      plastids, we studied their phylogeny on the basis of nearly complete 16S rRNA
      gene sequences. The data set comprised 15 strains of cyanobacteria from different
      morphological groups, 1 prochlorophyte, and plastids belonging to 8 species of
      plants and 12 species of diverse algae. This set included three cyanobacterial
      sequences determined in this study. This is the most comprehensive set of
      complete cyanobacterial and plastidial 16S rRNA sequences used so far.
      Phylogenetic trees were constructed using neighbor joining and maximum parsimony,
      and the reliability of the tree topologies was tested by different methods. Our
      results suggest an early origin of plastids within the cyanobacterial divergence,
      preceded only by the divergence of two cyanobacterial genera, Gloeobacter and
      Pseudanabaena.

PMID- 8524049
TI  - Molecular phylogeny of annexins and identification of a primitive homologue in
      Giardia lamblia.
AB  - The homologous repeats of annexin tetrads are believed to have originated by
      successive duplication and fusion from a putative monomeric precursor, but
      neither the nature of their ancestor nor the events leading to the formation of
      different subfamilies have been elucidated. We have performed molecular
      phylogenetic analysis of aligned annexin nucleotide and amino acids sequences to
      characterize subfamily branching, to delineate the temporal order of appearance
      of individual repeat units, and to gain insight into the origin and nature of the
      primordial unit. All extant annexins appear to have a common tetrad precursor
      that may have originated from a progenitor unit resembling repeat 3, followed by
      the generation of repeats 4, 1, and 2 from a more evolved progenitor with
      subsequent fusion. Repeat sequences of the earliest human annexins VII and XIII
      were used to identify alpha-giardin genes as primitive homologues from the
      unicellular protozoan Giardia lamblia, which diverged from eukaryote lineage 1
      1.5 billion yr ago. The significant homology between alpha-giardins and annexins
      suggested that the cell membrane adhesive role of these proteins may be a common,
      fundamental property of the annexin C-terminal core region. Purported annexin VII
      of Dictyostelium discoideum was reclassified as new annexin XIV, three
      Caenorhabditis elegans genes were assigned to new subfamilies XV, XVI, and XVII,
      and plant annexin XVIII from Medicago sativa was among the earliest diverging
      subfamilies. Annexins I and II were found to be closely related, but analysis of
      protein mutation rates confirmed that the former is evolving up to three times
      more rapidly. The inclusion of early phyla in annexin taxonomy provides a useful
      basis for assessing the structural and functional changes associated with annexin
      evolution.

PMID- 8524050
TI  - Gene products of Escherichia coli: sequence comparisons and common ancestries.
AB  - Sequences of 1,862 chromosomally encoded Escherichia coli K12 proteins were
      examined to identify genes likely to have arisen by duplication of genes in an
      ancestral chromosome. The criteria for sequence relatedness were an alignment of
      at least 100 amino acid residues and a PAM distance (number of accepted point
      mutations per 100 residues separating two sequences) below 250. A total of 971 of
      the 1,862 proteins examined were found in 2,329 sequence-related pairs that met
      these criteria. Most proteins of the sequence-related pairs were related in
      cellular function, as judged by biochemical and/or physiological features. Many
      of the pairs of proteins could be grouped into sequence-related families. If such
      groupings were generated from ancestral genes by duplication and divergence
      events, through these sequence comparisons we can identify putative ancestral
      sequences of the present-day genes of E. coli and other organisms. The results
      suggest that the 971 paralogous genes could have been derived from only 204
      ancestral genes. We have also shown that the process of duplication and
      divergence is not the exclusive mechanism of evolution of all E. coli genes.
      Indeed, the relationships among the sequences of multiple (in the sense of
      redundant) enzymes indicate that nearly half could have arisen either by
      convergent evolution or by lateral transfer. Therefore, not all functionally
      related genes need arise by duplication and divergence.

PMID- 8524051
TI  - Among-site rate variation and phylogenetic analysis of 12S rRNA in sigmodontine
      rodents.
AB  - We analyze sequences from two mitochondrial genes, cytochrome b (cyt b) and 12S
      rRNA (12S), for a group of sigmodontine rodents among which phylogenetic
      relationships are well understood based on concordance of morphological,
      chromosomal, allozyme, and other DNA data sets. Because these two genes are
      physically linked on the nonrecombining mitochondrial genome, they necessarily
      share the same history. Phylogenetic analysis of the cyt b gene recovers the well
      corroborated relationships, generally with strong support. None of the methods
      that we employed, including variously weighted parsimony, neighbor joining on
      both single-rate and gamma-corrected distances, and maximum likelihood, were able
      to recover these relationships for the 12S gene. Parsimony analyses of the 12S
      data resulted in a relatively strongly supported placement of Peromyscus eremicus
      that conflicts with that suggested by cyt b and all other data. There is extreme
      among-site rate variation in the 12S sequences and moderate levels in the cyt b
      sequences. This highly skewed distribution of rates in the 12S gene makes
      phylogenetic analyses of these sequences particularly susceptible to the
      misleading effects of nonindependence and other nonrandom noise, suggesting that
      phylogenetic analyses of data sets that contain a great deal of among-site rate
      variation be interpreted with caution.

PMID- 8524052
TI  - Rocky Mountain spotted fever in an endemic area in Minas Gerais, Brazil.
AB  - Only one species of spotted fever-group rickettsiae that is pathogenic for humans
      has been isolated in Brazil, where few physicians are familiar with this disease.
      In order to obtain information on tick-borne rickettsiosis, a study was performed
      in the County of Santa Cruz do Escalvado, State of Minas Gerais, Brazil, where a
      fatal clinical case confirmed by specific immunofluorescence had been reported.
      Serum samples obtained from 679 humans and 96 dogs were tested by indirect
      immunofluorescence for detectable antibodies to spotted fever-group rickettsiae,
      the criterion for a positive result being a titer > or = 1:64. Seropositivity was
      detected in 7.14% of the humans sera examined and 13.68% of the dogs. We discuss
      the significance of these findings and formulate some questions, emphasizing the
      need for further investigation.

PMID- 8524053
TI  - Hepatitis B and C prevalences among blood donors in the south region of Brazil.
AB  - The prevalence of hepatitis B and C infection has been determined in a
      seroepidemiological survey among blood donors from the south of Brazil
      (Florianopolis, State of Santa Catarina). These markers has also been correlated
      with the levels of alanine aminotransferase (ALT), a surrogate marker to prevent
      post-transfusion hepatitis. Sera from 5000 donors were randomly collected in the
      period of April to November 1991. The prevalences of HBsAg, anti-HBs and anti-HBc
      were respectively 0.78%, 7.02% and 13.98%. The anti-HCV prevalence after
      confirmation testing with line immunoassay (LIA), was 1.14%. Normal values of ALT
      ( < = 32 U/ml) were found in 59.78%, values slightly above the mean (ALT between
      32-70 U/ml) in 37.74% and high values of ALT ( > = 70 U/ml) in 2.48%. The
      positivity of anti-HCV antibodies increased with the elevation of ALT levels.
      This correlation was not observed in relation to HBsAg. There exists a diversity
      in the recognition of HCV epitopes among HCV positive donors. Via the
      confirmation test used, we could observe that 94.7% of donors recognize the
      structural core antigen. Besides that, we observed that 5.26% of the HCV reactive
      sera recognized only epitopes located in the NS4 and/or NS5 region, indicating
      the importance of these epitopes for the improvement of assays.

PMID- 8524054
TI  - Schistosomiasis mansoni in the region of the Triangulo Mineiro, State of Minas
      Gerais, Brazil.
AB  - In order to reevaluate the possible presence of schistosomiasis mansoni in the
      Triangulo Mineiro, one of the areas of the State of Minas Gerais where this
      parasite is not commonly found, malacological survey and fecal examinations were
      undertaken in the region between October 1990 and June 1992. A sample of 7,032
      1st grade school children from 29 counties had their feces examined using the
      Kato-Katz method. Amongst the children examined, two from Planura and one from
      each countie of Capinopolis, Conceicao das Alagoas, Uberaba, Uberlandia, Prata
      and Gurinhata were positive for Schistosoma mansoni. None of the children were
      identified as being autoctonous cases. In the malacological survey, 5,406
      planorbid snails were examined. The specimens were identified morphologically and
      examined for S. mansoni by squashing between glass plates. The species were
      identified as Biomphalaria tenagophila in three counties, as B. straminea in ten
      and B. intermedia in 16. No snails were found in eight other counties studies.
      The snails were found to be negative for S. mansoni. The presence of intermediate
      hosts for S. mansoni, associated with parasitized individuals emphasizes the
      necessity of epidemiological surveillance for schistosomiasis in the region of
      Triangulo in the State of Minas Gerais.

PMID- 8524055
TI  - Intratypic differentiation of polioviruses isolated from suspected cases of
      poliomyelitis in Brazil during the period of 1990 to 1993.
AB  - This study analyzed 3129 fecal samples derived from 1626 patients with sudden
      onset acute flaccid paralysis clinically compatible with poliomyelitis. The
      samples were collected in the period ranging from January 1990 to September 1993
      in all regions of Brazil. Among the 1626 cases studied, 196 had isolation of
      poliovirus. Nevertheless, it was observed that some factors influenced the
      isolation rate and the intratypic characterization of these polioviruses. No
      cases of acute flaccid paralysis has been found to be etiologically related with
      wild polioviruses.

PMID- 8524056
TI  - Outbreak of cutaneous leishmaniasis in the Rio Doce Valley, Minas Gerais, Brazil.

PMID- 8524057
TI  - Development of trypanosomatids in the phytophagous insect Dysdercus peruvianus
      (Hemiptera: Pyrrochoridae). A light and eletron microscopic study.
AB  - Experimental infections of the phytophagous Hemiptera Dysdercus peruvianus with
      different trypanosomatids were studied for up to 55 days by light microscopy
      while the course of infection with Leptomonas seymouri and the Leptomonas isolate
      49/553G.O. was analyzed by electron microscopy. Rates of infection of D.
      peruvianus varied according to the infecting flagellate. The lower part of the
      midgut was found to be the preferential site of colonization where most
      flagellates were found isolated or arranged in clumps or rosettes. Specialized
      junctional structures with host cells were never observed. Flagellates could also
      be seen inside midgut cells within a parasitophorous vacuole. Infection of
      haemocoele and salivary glands was also observed.

PMID- 8524058
TI  - Prevalence of human papillomavirus DNA in female cervical lesions from Rio de
      Janeiro, Brazil.
AB  - A hundred-sixty paraffin-embedded specimens from female cervical lesions were
      examined for human papillomavirus (HPV) types 6, 11, 16 and 18 infections by non
      isotopic in situ hybridization. The data were compared with histologic diagnosis.
      Eighty-eight (55%) biopsies contained HPV DNA sequences. In low grade cervical
      intraepithelial neoplasias (CIN I), HPV infection was detected in 78.7% of the
      cases, the benign HPV 6 was the most prevalent type. HPV DNA was detected in 58%
      of CIN II and CIN III cases and in 41.8% of squamous cell carcinomas (SCC).
      Histologically normal women presented 20% of HPV infection. Oncogenic HPV was
      found in 10% of these cases, what may indicate a higher risk of developing CINs
      and cancer. Twenty-five percent of the infected tissues contained mixed
      infections. HPV 16 was the most common type infecting the cervix and its
      prevalence raised significantly with the severity of the lesions, pointing its
      role in cancer pathogenesis. White women presented twice the cervical lesions of
      mulatto and African origin women, although HPV infection rates were nearly the
      same for the three groups (approximately 50%). Our results showed that HPV typing
      by in situ hybridization is a useful tool for distinguishing between low and high
      risk cervical lesions. Further studies are required to elucidate risk factors
      associated with HPV infection and progression to malignancy in Brazilian
      population.

PMID- 8524059
TI  - Helicobacter pylori in dyspeptic children and adults: endoscopic, bacteriologic
      and histologic correlations.
AB  - Using different bacteriological (urease test, Gram staining and culture) and
      histological (Steiner staining and modified Giemsa staining) techniques, we
      searched for the presence of Helicobacter pylori in the gastric antrum of 200
      dyspeptic Brazilian patients (106 females and 94 males aged 19 days to 81 years).
      The presence of bacteria was then correlated with the endoscopic and histological
      findings. H. pylori was present in 59.5% of the population studied. In Brazil,
      colonization occurs early, involving 37% of the dyspeptic population by 20 years
      of age. The presence of H. pylori in the gastric antrum was strongly associated
      with duodenal ulcer (P < 0.001) and a normal endoscopic examination did not
      exclude the possibility of colonization of the gastric antrum by H. pylori. The
      most sensitive test was the preformed urease test (89%). We conclude that more
      than one diagnostic method should preferably be used for the detection of H.
      pylori and that the presence of H. pylori is closely correlated with active
      chronic gastritis (P < 0.001).

PMID- 8524060
TI  - Characterization of the hemagglutinin receptor specificity and neuraminidase
      substrate specificity of clinical isolates of human influenza A viruses.
AB  - Six clinical isolates of influenza A viruses were examined for hemagglutinin
      receptor specificity and neuraminidase substrate specificity. All of the viral
      isolates minimally passaged in mammalian cells demonstrated preferential
      agglutination of human erythrocytes enzymatically modified to contain NeuAc alpha
      2,6Gal sequences, with no agglutination of cells bearing NeuAc alpha 2,3Gal
      sequences. This finding is consistent with the hemagglutination receptor
      specificity previously demonstrated for laboratory strains of influenza A
      viruses. The neuraminidase substrate specificities of the clinical isolates
      examined were also identical to that described for the N2 neuraminidase of recent
      laboratory strains of human influenza viruses. The H3N2 viruses all displayed the
      ability to release sialic acid from both alpha 2, 3 and alpha 2, 6 linkages. In
      addition, two clinical isolates of H1N1 viruses also demonstrated this dual
      neuraminidase substrate specificity, a characteristic which has not been
      previously described for the N1 neuraminidase. These results demonstrate that
      complementary hemagglutinin and neuraminidase specificities are found in recent
      isolates of both H1N1 and H3N2 influenza viruses.

PMID- 8524061
TI  - Rapid method using high performance liquid chromatography for the purification of
      tetanus toxoid.

PMID- 8524062
TI  - Schistosomicidal activity of alkylaminooctanethiosulfuric acids.
AB  - The schistosomicidal activity of a new series of alkylaminooctanethiosulfuric
      acids was studied in white Swiss mice infected with the L.E. strain of
      Schistosoma mansoni (Belo Horizonte, MG, Brazil). In a preliminary screening of
      six compounds, two derivatives - 2-[(1-methylpropyl)amino]-1-octanethiosulfuric
      acid and 2-[(1-methylethyl)-amino]-1-octanethiosulfuric acid - given orally in
      doses of 300 mg/kg/day for five consecutive days, caused interruption of the
      oviposition and the hepatic shift of more than 90% of the worms. Both compounds
      caused a significant reduction in worm burden and, interestingly, the female
      schistosomes were more susceptible. With the therapeutic schedule of two doses of
      800 mg/kg over a 20 day interval, the death of almost all the females and about
      50% of the males was observed. Female worms recovered from treated mice showed
      scattered vitteline glands. Results of in vitro experiments against different
      developmental stages of the parasite revealed the induction of paralysis and
      damage to the tegument membrane. The drugs presented no toxic effects on the
      animals.

PMID- 8524063
TI  - In vivo differentiation of Trypanosoma cruzi--1. Experimental evidence of the
      influence of vector species on metacyclogenesis.
AB  - Vector species has not hitherto been studied as influencing metacyclogenesis of
      Trypanosoma cruzi, while the role of the parasite strain has been frequently
      stressed as of dominant importance in this process. In order to fill this gap in
      our knowledge, metacyclogenesis was monitored in nine triatomine species. The
      first part of this paper presents photographs of the main and intermediate
      parasite stages in each vector species studied. In the second part of the study
      the proportional distribution of all these forms, as seen in Giemsa stained
      smears is summarized, thus providing an opportunity to analyze both: the length
      of time between the ingestion of the blood trypomastigotes and the appearance of
      metacyclic forms and the rates of developmental stages leading to these latter.
      The most remarkable observation was that metacyclogenesis rates in vivo appear to
      be vector dependent, reaching 50% in Rhodnius neglectus, 37% in its congener R.
      prolixus and being dramatically lower in the majority of Triatoma species (5% in
      T. sordida, 3% in T. brasiliensis and 0% in T. pseudomaculata) at the 120th day
      of infection. These observations suggest that through screening of different
      vector species it is possible to find some that are capable of minimizing or
      maximizing metacyclic production.

PMID- 8524064
TI  - Studies on the replication of Mayaro virus grown in interferon treated cells.
AB  - Mayaro virus grown in interferon treated infected cells has been characterized
      with regard to its ability to replicate in vertebrate (TC7) and invertebrate
      (Aedes albopictus) cells. Virus purified from interferon treated TC7 cells
      adsorbs and penetrates to the same extent as the control virus. During infection,
      these virus particles caused inhibition of host protein synthesis and synthesized
      the same spectrum of viral proteins as normal virus. This population however, was
      apparently more sensitive to interferon treatment. Electron microscopy of TC7
      cells showed the presence of numerous aberrant virus particles budding from the
      plasma membrane.

PMID- 8524066
TI  - Effect of temperature on different stages of Romanomermis iyengari, a mermithid
      nematode parasite of mosquitoes.
AB  - The effect of temperature (20 degrees-35 degrees C) on different stages of
      Romanomermis iyengari was studied. In embryonic development, the single-cell
      stage eggs developed into mature eggs in 4.5-6.5 days at 25-35 degrees C but,
      required 9.5 days at 20 degrees C. Complete hatching occurred in 7 and 9 days
      after egg-laying at 35 and 30 degrees C, respectively. At 25 and 20 degrees C, 85
      96% of the eggs did not hatch even by 30th day. Loss of infectivity and death of
      the preparasites occurred faster at higher temperatures. The 50% survival
      durations of preparasites at 20 and 35 degrees C were 105.8 and 10.6 hr
      respectively. They retained 50% infectivity up to 69.7 and 30.3 hr. The duration
      of the parasitic phase increased as temperature decreased. Low temperature
      favoured production of a higher proportion of females which were also larger in
      size. The maximum time taken for the juveniles to become adults was 14 days at 20
      degrees C and the minimum was 9 days at 35 degrees C. Oviposition began earlier
      at higher temperature than at lower temperature. However, its fecundic period was
      shorter at 20 degrees C than at 35 degrees C indicating enhanced rate of
      oviposition at 20 degrees C. Fecundity was adversely affected at 20 degrees C and
      35 degrees C. It is shown that the temperature range of 25 degrees-30 degrees C
      favours optimum development of R. iyengari.

PMID- 8524065
TI  - Sexual behaviour and stridulation during mating in Triatoma infestans (Hemiptera:
      Reduviidae).
AB  - Factors affecting mating behaviour in the bug Triatoma infestans were
      quantitatively studied in the laboratory. Experimental conditions were
      established so that the probability of copulation increased with the time elapsed
      since the first adult meal. Copulatory attempts by males did not vary as a
      function of time, but rejections by females became significantly less frequent
      with the post feeding time. Non-receptive females displayed four types of
      rejection behaviour, i.e. flattening, stridulation, evasion and abdominal
      movements. The occurrence of stridulation performed by females in a sexual
      context was observed in a regular fashion and was quantified for the first time
      in this species.

PMID- 8524067
TI  - Leishmania major and Toxoplasma gondii have opposite effects on cytokine
      synthesis by macrophages.

PMID- 8524068
TI  - Engineering cytokine secretion from Trypanosoma cruzi.

PMID- 8524069
TI  - Occurrence of Plesiomonas shigelloides in water environments of Rio de Janeiro
      city.
AB  - Fresh and salt water samples analyzed in Rio de Janeiro city showed the presence
      of Plesiomonas shigelloides. Forty-six strains were isolated from both
      environments. A high incidence of P. shigelloides was achieved in polluted fresh
      and salt waters as well as in samples from non-polluted streams. P. shigelloides
      isolates had biochemical characteristics similar to those already described in
      the literature. None of the isolates analyzed produced enterotoxin in the
      suckling mouse assay. Hemolytic activity against sheep and human type A
      erythrocytes was detected in the strains tested. The results of the antibiotic
      susceptibility tests indicated that all the isolates were susceptible to the
      cephalosporins, penicillins combined with a beta-lactamase inhibitor,
      aminoglycosides, imipenem, norfloxacin, tetracycline, chloramphenicol and
      trimethoprim-sulfamethoxazole. All the isolates were resistant to the
      penicillins.

PMID- 8524070
TI  - Development of a cyanobacterial biolarvicide.
AB  - Results of studies on a larvicidal cyanobacterium that expresses a Bti cryIVD
      gene fusion are reported. Genetically altered Agmenellum quadruplicatum PR-6 is
      shown to be toxic to larvae of three major genera of disease-bearing mosquitos.
      Factors affecting expression of Bti genes in cyanobacteria are discussed.

PMID- 8524072
TI  - Integrated control measures against Culex quinquefasciatus, the vector of
      filariasis in Recife.
AB  - Integrated control measures against Culex quinquefasciastus have been implemented
      in a pilot urban area in Recife, Brazil. About 3,000 breeding sites found within
      the operational area were responsible for very high mosquito densities recorded
      during the pretrial period. Physical control measures have been applied to cess
      pits before starting a series of 37 treatments of the other sites with Bacillus
      sphaericus strain 2362, over 27 months. In spite of the difficulties due to
      environmental conditions, very significant reductions in preimaginal population
      of C. quinquefasciatus were achieved and, as a consequence, low adult mosquito
      densities were maintained for a relatively long period of time. Entomological and
      environmental data gathered in this pilot project can contribute to design an
      integrated mosquito control program in Recife city.

PMID- 8524071
TI  - Anti-HCV prevalence and risk factors analysis in pregnant women in central
      Brazil.

PMID- 8524073
TI  - Some environmental and biological factors influencing the activity of
      entomopathogenic Bacillus on mosquito larvae in Brazil.
AB  - The influence of environmental and biological factors on the efficacy of Bacillus
      thuringiensis serovar israelensis and B. sphaericus as mosquito larvicides are
      reviewed. The importance of strain dependence, cultivating media/methods,
      mosquito species/specificity, formulations and their relation to mosquito feeding
      habits, as well as temperature, solar exposure, larval density and concomitant
      presence of other aquatic organisms are addressed with reference to the present
      status of knowledge in Brazil.

PMID- 8524074
TI  - Bacillus sphaericus mosquito pathogens in the aquatic environment.
AB  - The fate of Bacillus sphaericus spores in the aquatic environment was
      investigated by suspending spores in dialysis bags in fresh and seawater. Spore
      viability was lost more rapidly in seawater. Neither B. sphaericus nor B.
      thuringiensis israelensis (B.t.i.) spores mixed with pond sediment appeared to
      attach to the sediment. However, rapid decrease in B.t.i. toxicity suggested
      attachment of parasporal bodies to sediment. B. sphaericus toxin settled more
      slowly and less completely. B. sphaericus spores fed to larvae of four aquatic
      invertebrates were mostly eliminated from the animal gut in less than one week.
      An exception was the cranefly (Tipula abdominalis) where spores persisted in the
      posterior gut for up to five weeks.

PMID- 8524075
TI  - Life history of Pygidiopsis crassus n. sp. (Trematoda, Digenea, Heterophyidae) in
      the neotropical region.
AB  - The life cycle of Pygidiopsis crassus n. sp. was experimentally reproduced,
      starting from cercariae from naturally infected Littoridina parchappei collected
      from Lujan River and different ponds in Buenos Aires Province, Argentina.
      Metacercariae were found encysted in the body cavity of experimentally and
      naturally infected fishes Cnesterodon decemmaculatus and naturally infected
      Jenynsia lineata. Adults were obtained experimentally in chicks and mice. The
      natural host is unknown. The new species is compared with Pygidiopsis macrostomum
      Travassos 1928, from Rattus norvegicus and from Noctilio leporinus mastivus,
      differing in body and egg sizes, in the size relation of oral and ventral sucker
      and the shape of excretory vesicle.

PMID- 8524076
TI  - Biological control program against simuliids in the State of Sao Paulo, Brazil.
AB  - In Brazil, the use of biological vector-control methods has been largely confined
      to experimental research, with little or no application of such techniques by
      public institutions responsible for implementing control programs. The notable
      exceptions have been the black fly control program carried out by the Health
      Secretariat in the State of Sao Paulo. Since the 1980s, Sao Paulo's
      "Superintendencia de Controle de Endemias" has been conducting studies on the
      viability of using Bacillus thuringiensis (H-14) for simuliid control, and the
      results have been so encouraging that the agency has now incorporated this method
      into its Simuliid Control Program.

PMID- 8524077
TI  - Bacillus thuringiensis: fermentation process and risk assessment. A short review.
AB  - Several factors make the local production of Bacillus thuringiensis (Bt) highly
      appropriate for pest control in developing nations. Bt can be cheaply produced on
      a wide variety of low cost, organic substrates. Local production results in
      considerable savings in hard currency which otherwise would be spent on
      importation of chemical and biological insecticides. The use of Bt in Brazil has
      been limited in comparison with chemical insecticides. Although Bt is imported,
      some Brazilian researchers have been working on its development and production.
      Fermentation processes (submerged and semi-solid) were applied, using by-products
      from agro-industries. As the semi-solid fermentation process demonstrated to be
      interesting for Bt endotoxins production, it could be adopted for small scale
      local production. Although promising results had been achieved, national products
      have not been registered due to the absence of a specific legislation for
      biological products. Effective actions are being developed in order to solve this
      gap. Regardless of the biocontrol agents being considered atoxic and harmless to
      the environment, information related to direct and indirect effects of microbials
      are still insufficient in many cases. The risk analysis of the use of microbial
      control agents is of upmost importance nowadays, and is also discussed.

PMID- 8524078
TI  - Cloning of a fragment of the gene cryIVB from Bacillus thuringiensis var.
      israelensis coding for the aminoterminal segment of a 130 kDa larvicidal
      endotoxin.

PMID- 8524079
TI  - Development of a collection of bacteria causing meningitis in Rio de Janeiro from
      1990 to 1991.
AB  - From March 1990 to December 1992, the National Institute for Quality Control of
      Health-INCQS Research Collection received 1476 bacterial samples isolated from
      human cerebrospinal fluid of patients suspect of meningitis in Rio de Janeiro,
      from the Sao Sebastiao State Institute of Infectious Diseases (IEISS). Neisseria
      meningitidis was found in most of these materials, followed in smaller number by
      Haemophilus sp. and Streptococcus pneumoniae. The great majority of N.
      meningitidis strains was serogroup B, followed by serogroup C and a few strains
      of serogroup W135. More than 50% of the isolated bacterial agents came from the
      predominant 0-4 years age group. The majority of the strains were from patients
      in the region known as "Baixada Fluminense" (Low Lands). The aim of the work
      presented here is to obtain samples of meningitis cases in at least 70% of the
      State of Rio de Janeiro and develop a collaborative research between INCQS
      FIOCRUZ and the IEISS, in order to set up a collection of strains for future
      studies. However, despite work being carried out in a rather satisfactory way,
      difficulties still arise and have to be overcome, to survey data.

PMID- 8524080
TI  - Scanning electron microscopic study of Prosorhynchoides arcuatus (Linton, 1990)
      (Bucephalidae: Digenea).
AB  - Prosorhynchoides arcuatus (Linton, 1900) from the intestine of Pomatomus saltator
      (L.) from the Atlantic coast of the State of Rio de Janeiro is studied by
      scanning electron microscopy, with detailed description of tegumental spines.
      Comments on the synonymy of this species with Bucephalopsis callicotyle Kohn,
      1962 are made. The tegument of adult P. arcuatus presents scale like and serrated
      spines and uniciliated sensory papillae, distributed over the body surface and is
      compared with other digenetic trematodes.

PMID- 8524081
TI  - Bacillus thuringiensis subsp. oswaldocruzi and Bacillus thuringiensis subsp.
      brasiliensis, two novel Brazilian strains which determine new serotype H38 and
      H39, respectively.

PMID- 8524082
TI  - Giardia lamblia: isolation, axenization and characterization of a strain from an
      asymptomatic patient from Belo Horizonte, MG, Brazil.

PMID- 8524083
TI  - Optimization of a mouse immunization protocol with Paracoccidioides brasiliensis
      antigens.
AB  - The objectives of the present study were to optimize the protocol of mouse
      immunization with Paracoccidioides brasiliensis antigens (Rifkind's protocol) and
      to test the modulation effect of cyclophosphamide (Cy) on the delayed
      hypersensitivity response (DHR) of immunized animals. Experiments were carried
      out using one to four immunizing doses of either crude particulate P.
      brasiliensis antigen or yeast-cell antigen, followed by DHR test four or seven
      days after the last immunizing dose. The data demonstrated that an immunizing
      dose already elicited response; higher DHR indices were obtained with two or
      three immunizing doses; there were no differences between DHR indices of animals
      challenged four or seven days after the last dose. Overall the inoculation of two
      or three doses of the yeast-cell antigen, which is easier to prepare, and DHR
      test at day 4 simplify the original Rifkind's immunization protocol and shorten
      the duration of the experiments. The modulation effect of Cy on DHR was assayed
      with administration of 2.5, 20 and 100 mg/kg weight at seven day intervals
      starting from day 4 prior to the first immunizing dose. Only the treatment with
      2.5 mg Cy increased the DHR indices. Treatment with 100 mg Cy inhibited the DHR,
      whereas 20 mg Cy did not affect the DHR indices. Results suggest an
      immunostimulating effect of low dose of Cy on the DHR of mice immunized with P.
      brasiliensis antigens.

PMID- 8524084
TI  - Degree of host-parasite compatibility between Schistosoma mansoni and their
      intermediate molluscan hosts in Brazil.
AB  - The compatibility of Biomphalaria tenagophila, B. straminea and B. glabrata from
      Minas Gerais with different strains of Schistosoma mansoni was evaluated using
      the method of Frandsen (1979b) in standardized experiments. One hundred and fifty
      of each species of snail were individually exposed in the laboratory to 50
      miracidia of S. mansoni lines LE, SJ and AL. The cercariae from the infected
      snails were counted and used to calculate TCP/100 indices, which were compared
      with those of Frandsen (1979b). For B. tenagophila the TCP/100 indices varied
      from 37,996 to 74,266 (class II and III). The snail was poorly compatible with LE
      (class II) and compatible with SJ and AL (class III). For B. straminea the
      indices varied from 9,484 to 20,508. The snail was not very compatible with SJ
      (class I) and poorly compatible with LE and AL (class II). For B. glabrata the
      indices varied from 588,828 to 1,039,065. The snails was extremely compatible
      (class VI) with the three lines of S. mansoni. These results confirm the
      epidemiological importance of B. glabrata in Brazil followed by B. tenagophila
      and B. straminea.

PMID- 8524085
TI  - CD4+, CD8+ and CD4- CD8- T cell-subsets can confer protection against Leishmania
      m. mexicana infection.
AB  - We studied the role of CD4+, CD8+, CD4- CD8- T cells and IgG anti-Leishmania
      after infection or vaccination in the CBA/ca mouse. Mice were either infected
      with L. m. mexicana promastigotes or vaccinated with parasite-membrane antigens
      incorporated into liposomes. Successfully vaccinated mice were used as cell
      donors in adoptive transfer experiments. Naive, syngeneic recipients received
      highly-enriched CD4+, CD8+ or CD4- CD8- T cells from those two set of donors and
      challenged with live parasites. Our results showed that, both CD4+ and CD8+ T
      cells from infected or vaccinated donors conferred significant disease-resistance
      to naive recipients. In addition, adoptive transfer of CD4- CD8- T cells from
      vaccinated donors significantly delayed lesion growth in recipient mice. We
      concluded that vaccination of CBA mice correlates with the induction of
      protective CD4+, CD8+ and CD4- CD8- T cells and the synthesis of IgG anti
      Leishmania.

PMID- 8524086
TI  - Validity of serology for American trypanosomiasis with eluates from filter paper.
AB  - This study evaluates whether blood collected on filter paper kept at 4 degrees C
      and tested at different intervals of time (1, 7, 15, 30 and 60 days after
      collection) would present similar results when compared to the serum samples and
      whether the type of filter paper influences the results. Eluates from filter
      paper samples were tested for Trypanosoma cruzi antibodies using indirect
      immunofluorescence antibody test (IFAT), indirect haemagglutination (IHA) and
      enzyme-linked immunosorbent assay (ELISA) as reference, the antibody titer in
      sera. Analysis of data showed that results obtained with IFAT, IHA (cut off point
      = 1:40) and ELISA in sera had similar sensitivity and good concordance among
      reactions. The use of a multiple linear regression model indicated that titer
      fall in eluates occurs up to the 7th day after the collection, and it is more
      marked for samples with lower antibodies titers. However, no significant
      differences were observed by IFAT, IHA (cut off point = 1:20) and ELISA in the
      proportion of positive reactions between sera and eluates. The results also
      showed that Melitta, Klabin or Whatman (reference) filter papers could be
      indicated for surveys, since they have shown similar capacity of maintenance of
      anti-T. cruzi immunoglobulins.

PMID- 8524087
TI  - Multilocus enzyme electrophoresis study of Bacillus sphaericus.
AB  - Multilocus enzyme electrophoresis (MLEE) has been used in the study of some
      Bacillus species. In this work we applied MLEE and numerical analysis in the
      study of the Bacillus sphaericus group. B. sphaericus can be distinguished from
      other entomopathogenic Bacillus by a unique allele (NP-4). Within the species,
      all insect pathogens were recovered in the same phenetic cluster and all of these
      strains have the same band position (electrophoresis migration) on the agarose
      gel (ADH-2). The entomopathogenic group of B. sphaericus seems to be a clonal
      population, having two widespread frequent genotypes (zymovar 59 and zymovar
      119).

PMID- 8524088
TI  - Mechanism of action of Bacillus thuringiensis toxins.
AB  - The selectivity of Bacillus thuringiensis toxins is determined both by the toxin
      structure and by factors inherent to the insect. These toxins contain distinct
      domains that appear to be functionally important in toxin binding to protein
      receptors in the midgut of susceptible insects, and the subsequent formation of a
      pore in the insect midgut epithelium. In this article features necessary for the
      insecticidal activity of these toxins are discussed. These include toxin
      structure, toxin processing in the insect midgut, the identification of toxin
      receptors in susceptible insects, and toxin pore formation in midgut cells. In
      addition a number of B. thuringiensis toxins act synergistically to exert their
      full insecticidal activity. This synergistic action is critical not only for
      expressing the insecticidal activity of these toxins, but could also play a role
      in delaying the onset of insect resistance.

PMID- 8524089
TI  - Exploration of receptor binding of Bacillus thuringiensis toxins.
AB  - Wild type and mutant toxins of Bacillus thuringiensis delta-endotoxins were
      examined for their binding to midgut brush border membrane vesicles (BBMV).
      CryIAa, CryIAb, and CryIAc were examined for their binding to Gypsy moth
      (Lymantria dispar) BBMV. The binding of CryIAa and CryIAc was directly correlated
      with their toxicity, while CryIAb was observed to have lower binding than
      expected from its toxicity. The latter observation confirms the observation of
      Wolfersberger (1990). The "rule" of reciprocity of binding and toxicity is
      apparently obeyed by CryIAa and CryIAc, but broken by CryIAb on L. dispar.
      Alanine substitutions were made in several positions of the putative loops of
      CryIAa to test the hypothesis that the loops are intimately involved in binding
      to the receptor. The mutant toxins showed minor shifts in heterologous binding to
      Bombyx mori BBMV, but not enough to conclude that the residues chosen play
      critical roles in receptor binding.

PMID- 8524090
TI  - Biochemistry and mode of action of the Bacillus sphaericus toxins.
AB  - Bacillus sphaericus produces at least two toxins which are highly toxic to
      mosquito larvae. The binary toxin, which is comprised of proteins of 51.4 and
      41.9 kDa, is present in all highly insecticidal strains. The 100 kDa SSII-1 toxin
      is present in most highly insecticidal as well as the weakly insecticidal
      strains. The current status of studies on biochemistry and mode of action of
      these toxins is reviewed.

PMID- 8524091
TI  - Transfer of toxin genes to alternate bacterial hosts for mosquito control.
AB  - Mosquitoes are vector of serious human and animal diseases, such as malaria,
      dengue, yellow fever, among others. The use of biological control agents has
      provide an environmentally safe and highly specific alternative to the use of
      chemical insecticides in the control of vector borne diseases. Bacillus
      thuringiensis and B. sphaericus produce toxic proteins to mosquito larvae. Great
      progress has been made on the biochemical and molecular characterization of such
      proteins and the genes encoding them. Nevertheless, the low residuality of these
      biological insecticides is one of the major drawbacks. This article present some
      interesting aspects of the mosquito larvae feeding habits and review the attempts
      that have been made to genetically engineer microorganisms that while are used by
      mosquito larvae as a food source should express the Bacillus toxin genes in order
      to improve the residuality and stability in the mosquito breeding ponds.

PMID- 8524092
TI  - Measurement of nucleotide exchange and hydrolysis activities in
      immunoprecipitates.

PMID- 8524093
TI  - Determination of guanine nucleotides bound to Ras in mammalian cells.

PMID- 8524094
TI  - Purification of baculovirus-expressed human Sos1 protein.

PMID- 8524095
TI  - Ras-Cdc25 and Rho-Dbl binding assays: complex formation in vitro.

PMID- 8524096
TI  - Purification of baculovirus-expressed recombinant Ras and Rap proteins.

PMID- 8524098
TI  - Measurement of Ras-bound guanine nucleotide in stimulated hematopoietic cells.

PMID- 8524097
TI  - Analysis of interaction between Ras and CDC25 guanine nucleotide exchange factor
      using yeast GAL4 two-hybrid system.
AB  - Our results demonstrate that the GAL4 two-hybrid system can be useful for
      studying interactions of the wild-type and mutant forms of Ras proteins with the
      CDC25 guanine nucleotide exchange factor (CDC25-GEF). In addition, our findings
      show that a negative result in the GAL4 two-hybrid system does not indicate that
      the two proteins tested do not interact under all conditions but only that they
      do not interact under the specific conditions examined. We recommend that the two
      hybrid system be employed in combination with other approaches, including
      molecular genetic analyses and in vitro binding experiments, for the study of Ras
      and CDC25-GEF interactions.

PMID- 8524099
TI  - Measurements of GTP/GDP exchange in permeabilized fibroblasts.

PMID- 8524100
TI  - Intrinsic and GTPase-activating protein-stimulated Ras GTPase assays.

PMID- 8524101
TI  - Determination of Ras and GTPase-activating protein interactions by kinetic
      competition assay.

PMID- 8524102
TI  - Phosphorylation-dependent complexes of p120 Ras-specific GTPase-activating
      protein with p62 and p190.

PMID- 8524103
TI  - Analysis of Ras protein expression in mammalian cells.

PMID- 8524104
TI  - Purification of recombinant Ras GTPase-activating proteins.

PMID- 8524105
TI  - Vaccinia virus expression of p21 rasAsn-17.

PMID- 8524106
TI  - Inducible expression of Ras N17 dominant inhibitory protein.

PMID- 8524107
TI  - Prenylation and palmitoylation analysis.

PMID- 8524108
TI  - Immune complex kinase assays for mitogen-activated protein kinase and MEK.

PMID- 8524109
TI  - Cell-free assay system for Ras-dependent MEK activation.

PMID- 8524110
TI  - Preparation and use of semiintact mammalian cells for analysis of signal
      transduction.

PMID- 8524111
TI  - Mitogen-activated protein kinase activation by scrape loading of p21ras.

PMID- 8524112
TI  - Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and
      Raf.

PMID- 8524113
TI  - Assay of MEK kinases.

PMID- 8524114
TI  - Refolding and purification of Ras proteins.

PMID- 8524115
TI  - Activation of Raf-1 by Ras in intact cells.

PMID- 8524116
TI  - Purification of baculovirus-produced Rap1 GTPase-activating protein.

PMID- 8524117
TI  - Ras-Raf complexes: analyses of complexes formed in vivo.

PMID- 8524118
TI  - Ras-Raf complexes in vitro.

PMID- 8524119
TI  - Ras-Raf interaction: two-hybrid analysis.
AB  - The identification of proteins mediating Ras effects, such as the
      serine/threonine kinases of the Raf family, has advanced our understanding of how
      signals are transmitted from the extracellular milieu to the nucleus. The
      modified two-hybrid system has proved to be a powerful tool for identifying
      specific protein interactions, such as those between Ras and Raf. We hope that
      the insight gained from the Ras screen, as well as insights from other two hybrid
      screens, will prove valuable in the application of this system to other enigmatic
      questions in biology.

PMID- 8524120
TI  - Methods for analyzing c-Jun kinase.

PMID- 8524121
TI  - Use of tyrosine-phosphorylated proteins to screen bacterial expression libraries
      for SH2 domains.

PMID- 8524122
TI  - Detection of SH3-binding proteins in total cell lysates with glutathione S
      transferase-SH3 fusion proteins: SH3 blot assay.

PMID- 8524123
TI  - Inhibition of Ras function in vitro and in vivo using inhibitors of farnesyl
      protein transferase.

PMID- 8524124
TI  - Assays for inhibitors of CAAX farnesyltransferase in vitro and in intact cells.

PMID- 8524125
TI  - Rat embryo fibroblast complementation assay with ras genes.

PMID- 8524126
TI  - Biological assays for Ras transformation.
AB  - The rodent fibroblast systems described above have provided sensitive and rapid
      biological assays to characterize the properties of normal and mutated Ras
      proteins. Furthermore, these assays have provided in vitro systems to measure the
      ability of other cellular components to modulate Ras signal transduction and
      transformation. However, while these assays provide an excellent measure of Ras
      transforming activity, the fact that these cells are of fibroblastic origin, and
      can be transformed by a single hit, indicates that caution should be used in
      extrapolating observations from NIH 3T3 transformation assays to the situation in
      human tumors. Therefore, using human epithelial cell-based assays that more
      closely approximate the cell types where mutated ras alleles are most frequently
      detected may provide more realistic assays for examining the biochemical and
      biological consequences of aberrant Ras function in human tumors. Nevertheless,
      despite these cautions, these rodent transformation assays will continue to be
      the best and most widely applied assays for Ras biological activity.

PMID- 8524127
TI  - Ras-mediated transcription activation: analysis by transient cotransfection
      assays.

PMID- 8524128
TI  - Oocyte microinjection assay for evaluation of Ras-induced signaling pathways.

PMID- 8524129
TI  - Mammalian cell microinjection assay.

PMID- 8524130
TI  - Detection of point mutations in Ras in tumor cell lines by denaturant gradient
      gel electrophoresis.

PMID- 8524131
TI  - Diagnostic detection of mutant ras genes in minor cell populations.

PMID- 8524132
TI  - Prenylation analysis of bacterially expressed and insect cell-expressed Ras and
      Ras-related proteins.

PMID- 8524133
TI  - RAS in yeast: complementation assays for test of function.

PMID- 8524134
TI  - Yeast adenylyl cyclase assays.

PMID- 8524135
TI  - Purification of human neutrophil NADPH oxidase cytochrome b-558 and association
      with Rap 1A.
AB  - The availability of sufficient quantities of highly purified phagocyte cytochrome
      b-558 has been necessary for many of the biochemical and immunological analyses
      of this important NADPH oxidase component, and it was only through the analysis
      of highly purified cytochrome b that the subunit composition was elucidated and
      the small subunit (p22-phox) was cloned and sequenced. In addition, the
      association of the small GTP-binding protein Rap1A with cytochrome b-558 was
      discovered through the analysis of purified cytochrome b. The procedures
      described here provide an easy, efficient, and highly reproducible method for the
      purification of cytochrome b as well as cytochrome b-Rap1A complexes. The ability
      to purify cytochrome b and cytochrome b-Rap1A complexes will also allow further
      analysis of the structure of this novel plasma membrane redox protein and the
      role of its association with low molecular weight GTP-binding proteins in the
      structure and regulation of the phagocyte NADPH oxidase.

PMID- 8524137
TI  - Screening phage-displayed random peptide libraries for SH3 ligands.

PMID- 8524136
TI  - Use of yeast two-hybrid system to evaluate Ras interactions with neurofibromin
      GTPase-activating protein.

PMID- 8524138
TI  - Reticulocyte lysate assay for in vitro translation and posttranslational
      modification of Ras proteins.

PMID- 8524139
TI  - Carboxyl methylation of Ras-related proteins.

PMID- 8524140
TI  - Use of yeast for identification of farnesyltransferase inhibitors and for
      generation of mutant farnesyltransferases.

PMID- 8524141
TI  - Analysis of intrinsic and CDC25-stimulated guanine nucleotide exchange of p21ras
      nucleotide complexes by fluorescence measurements.

PMID- 8524142
TI  - Precursors of quinone tanning: dopa-containing proteins.

PMID- 8524143
TI  - Cloning of mammalian topa quinone-containing enzymes.

PMID- 8524144
TI  - Isolation of active site peptides of lysyl oxidase.

PMID- 8524145
TI  - Resonance Raman spectroscopy of quinoproteins.

PMID- 8524146
TI  - Redox-cycling detection of dialyzable pyrroloquinoline quinone and quinoproteins.

PMID- 8524147
TI  - Tryptophan tryptophylquinone in bacterial amine dehydrogenases.

PMID- 8524148
TI  - Model studies of cofactor tryptophan tryptophylquinone.

PMID- 8524149
TI  - Detection of intermediates in tryptophan tryptophylquinone enzymes.

PMID- 8524150
TI  - X-ray studies of quinoproteins.

PMID- 8524151
TI  - Isolation of 2,4,5-trihydroxyphenylalanine quinone (topa quinone) from copper
      amine oxidases.

PMID- 8524152
TI  - Genetics of bacterial quinoproteins.

PMID- 8524153
TI  - Biogenesis of pyrroloquinoline quinone from 3C-labeled tyrosine.

PMID- 8524154
TI  - X-ray crystallographic studies of cofactors in galactose oxidase.

PMID- 8524155
TI  - Spectroscopic studies of galactose oxidase.
AB  - A combination of powerful spectroscopic approaches is now available for detailed
      characterization of active sites in free radical metalloenzymes. As illustrated
      for galactose oxidase, a single approach such as EPR or absorption spectroscopy
      is not sufficient to characterize a sample completely, and only by combining
      results from complementary techniques can the information in each approach be
      used most effectively.

PMID- 8524156
TI  - Use of rapid kinetics methods to study the assembly of the diferric-tyrosyl
      radical cofactor of E. coli ribonucleotide reductase.
AB  - The SF-Abs, RFQ-EPR, and RFQ-Moss data on the R2 reconstitution reaction are all
      consistent with the mechanism of Scheme I, in which the intermediate X is the
      immediate precursor to the product cofactor, and illustrate how the continuous SF
      approach and the discontinuous RFQ methods can be complementary. Given the
      inherent differences in the methods, it should not be taken for granted that data
      from the two will be consistent. A number of problems can be associated with the
      RFQ approach. For example, isopentane could conceivably interfere with or alter
      the chemistry to be studied. A second potential problem involves temperature
      dependent equilibria among different intermediate species. This problem has been
      encountered by Dooley et al. with the 6-hydroxydopa-requiring protein, plasma
      amine oxidase and was previously observed with the adenosylcobalamin-dependent
      ribonucleotide reductase by Blakley and co-workers. This potential complication
      should be considered when discrepancies arise between SF and RFQ data and in low
      temperature structural studies of reactive intermediates in general. Each of the
      three methods employed can yield time-resolved quantitation of reaction
      components. In this regard, SF-Abs has the disadvantage of poor resolution, such
      that quantitation of individual components most often requires sophisticated
      mathematical analysis. Obvious advantages to the RFQ-Moss method are the presence
      of an internal standard (the known amount of 57Fe being proportional to the total
      absorption area) and the spectroscopic activity of all reaction components which
      contain iron. In our hands, quantitation by RFQ-EPR was most problematic and
      least reproducible. This irreproducibility most likely relates to heterogeneity
      among samples in terms of volume and density. As discussed in detail by Ballou
      and Palmer, the packing factor, which relates to the fraction of a sample made up
      by the reaction solution (the remainder being frozen isopentane), is dependent on
      the investigator. Given this caveat, it is not surprising that the RFQ-EPR data
      had the greatest uncertainty in our hands. Placing a chemically unreactive, EPR
      active standard in each reaction mixture could help alleviate this problem. Time
      resolved Moss methods can be extremely powerful if excellent, nonoverlapping
      reference spectra of starting materials, products, and intermediates are
      available. All of the iron centers can be examined simultaneously. The problems
      associated with Moss arise from its extreme insensitivity. It takes millimolar
      solutions of proteins and several days for data collection of each time
      point.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8524157
TI  - Tyrosyl radicals in photosystem II.

PMID- 8524158
TI  - Role of tryptophans in substrate binding and catalysis by DNA photolyase.

PMID- 8524159
TI  - Spectrophotometric detection of topa quinone.

PMID- 8524160
TI  - Glycyl free radical in pyruvate formate-lyase: synthesis, structure
      characteristics, and involvement in catalysis.

PMID- 8524161
TI  - Characterization of a radical intermediate in the lysine 2,3-aminomutase
      reaction.

PMID- 8524162
TI  - Role of oxidized amino acids in protein breakdown and stability.

PMID- 8524163
TI  - Model studies of topa quinone: synthesis and characterization of topa quinone
      derivatives.

PMID- 8524164
TI  - Catalytic aerobic deamination of activated primary amines by a model for the
      quinone cofactor of mammalian copper amine oxidases.

PMID- 8524165
TI  - Detection of reaction intermediates in topa quinone enzymes.

PMID- 8524166
TI  - Mass spectrometric studies of the primary sequence and structure of bovine liver
      and serum amine oxidase.

PMID- 8524167
TI  - The impact of chronic reduced microcirculation on tissue function and on
      neoplastic promotion.
AB  - I hypothesize that chronic reduced microcirculation, even limited to micro areas
      of tissue, may lead to respiratory deficiencies, to a proliferation of simplified
      cells as a result of a lack of energy, and to defects in immune control. In these
      situations, reduce resistance and specific hypofunction might occur in organs
      (should the entire organ be involved) and cell alterations might come about, as
      several authors have described experiments in conditions of hypoanoxia. The
      mutated cells, possibly in these areas as well, could more easily emerge as
      neoplasia because they are removed from immune control and surrounded by a
      terrain of reduced resistance. Infant leukaemias would be easier to control than
      adult forms because it is harder for antineoplastics to reach the latter's site
      of origin.

PMID- 8524168
TI  - A unified model for cell-killing by heat: interpretation of continuous, step
      down, step-up and split heating.
AB  - We have already proposed a model for the lethal effects of heat on cells. In the
      model, a three-step process for cellular inactivation was hypothesized: 1)
      heating produces sublethal damage; 2) the damage is repaired in a certain time
      period; 3) the cell is inactivated when it undergoes cumulative sublethal damage
      to the extent that it cannot be repaired. Using the previous model, we
      investigated the modifications of the survival curve in 1) continuous heating, 2)
      step-down heating, 3) step-up heating, and 4) recovery from the thermal injury by
      split heating. These four phenomena were explained well with the mathematical
      model.

PMID- 8524169
TI  - A set-theoretical requirement for nonphysical specificity in embodied evaluations
      of physical models of mind.
AB  - When confronting assertions that minds are physically driven, humans necessarily
      engage their capacity to imagine objects moving in ways unexhibited in visual
      examples of physical phenomena. This variety of mental imagery, however, being
      unspecifiable in a given human in point-to-point mappings on to physically
      constrained events (even in principle), therefore has a physically undefined
      necessity. Intervention in neurologic patients, therefore, if done according to
      criteria no more comprehensive than those delimiting physical paths from stimuli
      to responses, could not provide for that necessity. Provision for necessarily
      embodied mental imagery might be feasible if, in a given human, every progression
      through that human's mental space is permitted unique specification in
      mathematical hypotheses of brain.

PMID- 8524170
TI  - The role of vitamin D3 in the aetiology of abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysms (AAAs) have traditionally been attributed to
      atherosclerosis, although there is increasing epidemiological, biochemical and
      genetic evidence that aneurysmal arterial disease is different from occlusive
      atherosclerosis. One of the most consistent biochemical findings in the
      aneurysmal aorta is a significant reduction in elastin protein; the cause, for
      this remains unclear. There is in vitro evidence that vitamin D3 (1,25
      dihydrocholecalciferol) inhibits the production of elastin by smooth muscle
      cells. On the basis of this observation and the possibility that some subjects
      may be exposed to excess vitamin D3, the hypothesis that vitamin D3 may be a
      previously unrecognized aetiological factor in the pathogenesis of AAA is
      developed.

PMID- 8524171
TI  - The nitric oxide/ascorbate cycle: how neurones may control their own oxygen
      supply.
AB  - The brain requires an extremely precise means of controlling oxygen delivery to
      neurones. Too much, and the cells risk free-radical-mediated damage: too little,
      and the neurones die from hypoxic-excitotoxic mechanisms. Although nitric oxide
      (NO) is a powerful vasodilator in cerebral blood vessels, synthesis of NO from
      arginine requires oxygen and so is unsuitable as the mediator of hypoxia-induced
      cerebral vasodilation. This paper describes a model in which ascorbate, released
      from neurones during activity, generates NO from the reduction of nitrite ions in
      the extracellular space. This mechanism could subtly and accurately match the
      oxygen transport to the local metabolic demands of the nerve cells. The model
      predicts that the consequences of low ascorbate in the brain would be progressive
      damage from inaccurate oxygen delivery.

PMID- 8524172
TI  - Does xenogeneic demineralized bone matrix have clinical utility as a bone graft
      substitute?
AB  - Autologous bone harvested from the iliac crest is a commonly used grafting
      material for a number of surgical procedures; however, there is documented
      morbidity associated with secondary site harvesting. Because demineralized bone
      matrix (DBM) is inherently osteoinductive (i.e., it facilitates differentiation
      of uncommitted connective tissue cells into bone-forming cells), it has potential
      appeal as a bone-graft substitute. Allogeneic DBM usage has intrinsic
      shortcomings related to procuring, processing and characterizing bone from a
      human donor pool. Xenogeneic bone represents an unlimited supply of available
      material if it can be processed to render it safe for transplantation to the
      human host. It is hypothesized that reported immunogenicity and non-viability of
      xenogeneic DBM results from lipids and plasma proteins not removed during typical
      demineralization processes. The authors propose a rigorous examination of this
      hypothesis, followed by several pivotal studies to determine the effectiveness of
      xenogeneic DBM.

PMID- 8524173
TI  - A mechanism of action underlying the antidepressant effect of light.
AB  - In patients with winter seasonal affective disorder (SAD), delayed and reduced
      responses to corticotropin-releasing factor (CRF) have been observed. Bright
      light treatment has been shown to normalize these responses. In depressed
      patients, there is increased CRF activity in the evening during the normally
      quiescent period between 19.30 and 22.00 hours. In patients with winter SAD, the
      level of subjective sleepiness is increased in the evening between 20.00 and
      21.00 hours. In the latter group of patients, the CRF activity may be increased
      in the evening and associated with the increased level of subjective sleepiness.
      This increased activation is suggested to be normalized by bright light
      treatment, acting primarily on neurons of the paraventricular nucleus of the
      hypothalamus.

PMID- 8524174
TI  - Estrogen could control photoperiodic adjustment in seasonal affective disorder.
AB  - Women are affected by winter seasonal affective disorder (SAD) more often than
      men. The female/male ratio is reported to range from 2:1 to 40:1 in samples of
      patients with winter SAD. It is suggested that this preponderance of women is
      based on the action of the ovarian steroid hormones estrogen and progesterone.
      However, the detailed mechanisms of action are not well understood to date. A new
      hypothesis claims that, in women with winter SAD, decreased levels of estradiol
      in the ventromedial hypothalamus are associated with the occurrence of atypical
      symptoms of depression, including increased daytime sleepiness and hypersomnia
      during the winter.

PMID- 8524175
TI  - Airway smooth muscle proliferation in asthma: the potential of vascular leakage
      to contribute to pathogenesis.
AB  - Proliferation of the non-vascular smooth muscle in the walls of the bronchi and
      bronchioles is a prominent histopathological feature of asthma and is thought to
      contribute to airway hyperreactivity and narrowing. Increased vascular
      permeability with plasma leakage is also a feature of asthma pathology and causes
      submucosal oedema. We hypothesize that, in asthmatics, the accumulation of
      enriched plasma in the environment surrounding airway smooth muscle promotes
      respiratory smooth muscle mitogenesis and hyperplasia. This situation represents
      the in vivo correlate of the increase in airway smooth muscle cell growth seen in
      vitro with increasing concentrations of serum in the culture medium. Thus, we
      hypothesize that vascular leakage in the airways in asthma is a primary
      pathogenic event leading to airway smooth muscle hyperplasia and hypertrophy, and
      consequently airway narrowing, promoting the characteristic bronchial
      hyperreactivity associated with narrowing of the airway lumen.

PMID- 8524176
TI  - Diabetic cardiomyopathy: the significance of creatine.
AB  - Diabetics exhibit a greater incidence of cardiovascular disease than non
      diabetics. The vascular changes that occur are well documented and are thought to
      promote other clinical manifestations such as cardiomyopathy. Research has shown
      that the pathogenic events in the myocyte may occur independently of
      atherosclerotic processes. The atherosclerotic changes in diabetes involve non
      enzymatic glycation of extracellular basement membrane proteins. We hypothesize
      that intracellular glycation events occur in cardiac tissue that alter
      intermediary metabolism, particularly Ca2+ homeostasis, which leads to cell
      dysfunction. Additionally, we hypothesize that the high steady state
      intracellular concentrations of unphosphorylated creatine may offer protection
      against the formation of advanced glycation endproducts by reacting directly with
      glucose metabolites that may have reached toxic levels in the myocyte of
      diabetics.

PMID- 8524178
TI  - Master-slave gene entrainment and soliton dynamics.
AB  - The paper discusses a type of transcriptional entrainment between master-slave
      genes that is occasioned by the translation of a solitonic kink along the stack
      of a coiled chromatid.

PMID- 8524177
TI  - Reflections on an interface.
AB  - This discusses an immune recognition model of autoimmunity and tolerance which is
      based on an idiotypic and an anti-idiotypic immune network response at a virus
      receptor interface.

PMID- 8524179
TI  - Mechanism of the effect of thermotherapy as applied to AIDS.
AB  - Artificially induced thermal intermittence using thermogenic agents was utilized
      to treat AIDS patients in an attempt to make an analogy with the sterilization
      process by tyndallization employed in laboratories. It is known that micro
      organisms are more sensitive to discontinuous than to constant heat. The author
      believes that the AIDS virus may be either destroyed or weakened using this
      method which may also provoke an immune stimulus over the body's system of
      defense, especially over the bone marrow, with the consequent increase of the
      indexes of lymphocins, opsonins and hematogenesis.

PMID- 8524180
TI  - Gene-gene coordination by the nuclear envelope.
AB  - The paper studies how certain topologic features of the nuclear envelope may
      reorganize entrained transcription via spatial rearrangements of genes carried by
      distinct chromatids.

PMID- 8524181
TI  - Contribution of class I HLA-A2 antigen in immune reactions.
AB  - The involvement of the Class I HLA-A2 antigen is briefly reviewed in relation to
      allograft rejection, the feto-maternal relationship, viral cytotoxic reactions
      and tumor immunity. It is suggested that the HLA-A2 molecule may have, as
      compared to other HLA Class I alleles, a dominant role as a restricting element
      in cytotoxic T-cell recognition in the feto-maternal relationship to male
      fetuses, in specific viral infections and in tumors. As compared to other HLA
      Class I alleles, its reduced expression or loss in a variety of tumors suggests
      its possible important role in tumor immune surveillance. The disappearance of
      HLA-A2 from tumor cells may eventually contribute to the escape from T-cell
      recognition of malignant cells.

PMID- 8524182
TI  - Hypothesis: spermine may be an important epidermal antioxidant.
AB  - Spermine has been identified as a potent antioxidant and an anti-inflammatory
      agent. The compound is present in all organisms and all organs. The concentration
      is exceptionally high in skin, and I propose that spermine constitutes a prime
      defence against radiation damage. This hypothesis is substantiated by the fact
      that ornithine decarboxylase (ODC), the rate-controlling enzyme of spermine
      biosynthesis, is induced by UVB-irradiation and oxidative stress. On the
      contrary, inhibition of ODC makes cells more sensitive to radiation damage. The
      antioxidative effect of spermine may be due to metal chelation and/or to
      prevention of superoxide generation from stimulated neutrophils. This paper
      reviews the antioxidative and anti-inflammatory effects of spermine, and suggests
      that spermine is an important antioxidant of epidermis.

PMID- 8524183
TI  - Calcium supplementation prevents pregnancy-induced hypertension by increasing the
      production of vascular nitric oxide.
AB  - Pregnancy-induced hypertension (PIH) remains a common cause of maternal and fetal
      morbidity and mortality. During the past 7 years, some progress has been made in
      the prevention of PIH. Specifically, clinical studies have shown that
      supplementation with calcium can significantly reduce the frequency of PIH,
      specially in populations with a low calcium intake. We have suggested that, in
      such a population, calcium supplementation is a safe and effective measure for
      reducing the frequency of PIH. Thus, the purpose of this article is to advance a
      hypothesis about the mechanism by which calcium supplementation reduces the risk
      of PIH. We propose that dietary calcium supplementation reduces the frequency of
      PIH by maintaining the serum ionized calcium level which is crucial for the
      production of endothelial nitric oxide, the increased generation of which
      maintains the vasodilatation that is characteristic of normal pregnancy.

PMID- 8524184
TI  - Progression of cancer.
AB  - Carcinoma constitution originates in the hetero duplication mitoses which divide
      non-maturable stem cells into two different types of daughter cells: maturable
      and non-maturable cancerous stem cells. Throughout the progression of such
      mitoses the organoid continuity of the cancer depends only on the non-maturable
      daughter stem cells, not on the maturable ones. This type of cancer can be
      considered non-progressive or to be in the incubation stage, as it only enables
      cancer tissue to preserve its organoid continuity without allowing progressive
      growth. However, when an occasional mitotic phase of the hetero-duplication
      mitotic progression undergoes genuine cell-phase duplication mitosis, this non
      progressive or incubation stage of cancer is converted to a progressive type of
      cancer. This conversion is dependent on the reappearance of the complete mitotic
      condition of the mitotic maturation promoting system (MMPS) containing an
      abnormal supplement. Thus, a thorough investigation of the abnormal supplement
      and the reappearance of the complete mitotical condition is an essential part of
      research efforts to prevent and eradicate cancer.

PMID- 8524185
TI  - Unexplained stillbirths and sudden infant death syndrome.
AB  - Comparison of necropsy records, clinical details and epidemiological data of 93
      unexplained stillbirths and 149 cases of sudden infant death syndrome provides
      compelling evidence that these disorders represent a continuum of a single
      spectrum of disease. Regarding them as a single disease entity could lead to a
      clearer understanding of both.

PMID- 8524186
TI  - Hodgkin's disease as an indicator of AIDS.
AB  - Hodgkin's disease (HD) is not currently included within the Centers for Disease
      Control (CDC) classification system for AIDS. Upon HD diagnosis, HIV(human
      immunosuppressive virus)-positive patients are generally found within Stages III
      or IV of the Ann Arbor HD classification system, already exacerbating the problem
      of treatment. In contrast, HIV-negative patients diagnosed with HD are generally
      found within Stages I or II. Epidemiology and the presence of secondary
      lymphomas, opportunistic infections, or aggressive pathologies, accompanied by
      low survival rate and timing of HD diagnosis suggest that HD should be included
      among conditions indicating AIDS manifestation.

PMID- 8524187
TI  - The adjuvant use of macrophage colony stimulating factor in tattoo removal using
      laser surgery.
AB  - Tattoos are acquired pigmented lesions of the skin that may be removed with laser
      surgery. Following laser treatment, macrophages engulf the altered pigment. The
      activity of macrophages can be influenced by macrophage colony-stimulating
      factor. In order to evaluate the potential adjunctive use of macrophage colony
      stimulating factor in tattoo removal using laser surgery, a prospective study,
      initially in an animal model, to serially evaluate the clinical and
      histopathologic clearing of tattoo pigment following laser surgery at variable
      macrophage colony-stimulating factor dose concentrations and injection schedules,
      could be performed. Since the clearing of tattoo pigment following laser surgery
      is influenced by the presence of macrophages at the site of treatment, and since
      macrophage colony-stimulating factor influences macrophage activity, it is
      logical to hypothesize that the adjuvant use of this cytokine to recruit
      additional macrophages could expedite the removal of tattoo pigment following
      laser surgery.

PMID- 8524188
TI  - Combined spinal-epidural-general anesthesia.
AB  - Each one of the three kinds of anesthesia (spinal, epidural, general) has its
      advantages and disadvantages. A new concept of combined spinal-epidural-general
      anesthesia (CSEGA) is illustrated with the objective of producing a new kind of
      anesthesia. The aim is to draw out the good from each compartment. CSEGA can be
      based on muscle relaxation and anesthesia on its spinal part with the epidural
      augmentation. The endotracheal intubation can be kept in place with a very small
      dose of an inhalational anesthetic. There is no need for muscle relaxant drugs,
      i.v. opioids or benzodiazepines, for postoperative analgesia serves the epidural
      catheter. Very small doses of local anesthetic drugs injected into the spinal or
      epidural compartments, could be all that is needed for operations on any part of
      the body, including thorax and head. CSEGA is a new concept in anesthesia. The
      mixing of regional anesthesia with general anesthesia affords the
      anesthesiologist the opportunity to lower the local anesthetic doses, avoid using
      many kinds of intravenous drugs (muscle relaxants, opioids, benzodiazepines,
      etc.) and to approach a kind of anesthesia that is closer to the ideal.

PMID- 8524189
TI  - Werner syndrome and genetic obesity: speculation.
AB  - Werner syndrome (WS) is a rare autosomal recessive disease with poor growth,
      premature aging, scleroderma-like skin changes, endocrine abnormalities, and
      deficiencies of adipose tissue. Could there be a genetic obesity syndrome which
      offers an instructive contrast to at least one form of WS? At least one form of
      WS might result from an enzyme defect that causes hypertriglyceridemia,
      hyperinsulinism, and hyperglucagonism; the defective enzyme might play a key role
      in the utilization of tryptophan, riboflavin (vitamin B2), or other vitamins or
      in the synthesis of prostaglandins that inhibit insulin secretion. At least one
      form of genetic obesity might result from an enzyme defect that causes
      hypotriglyceridemia and hyperinsulinism without hyperglucagonism; the defective
      enzyme might be unable to bind properly to a product that inhibits some step in
      the process of conversion of free fatty acid (FFA) CoA into ketoacids.

PMID- 8524190
TI  - Pathogenic effects of the human chemical biofield.
AB  - Organisms release their antigens into the environment. Some antigens are volatile
      and may pass into the blood of other organisms during respiration. Fetal antigens
      enter the mother's bloodstream through the placenta. Foreign antigens in the
      blood can cause various chemical changes and may initiate an immune reaction.

PMID- 8524191
TI  - Expressed emotion and a hypothetical model of relapse in schizophrenia.
AB  - A hypothetical model is proposed that connects the risk of relapse in
      schizophrenia and expressed emotion in relatives with genetic factors in the
      individual, familial schizophrenia, severity of illness, family psychopathology,
      age of onset of the illness, and length of family exposure to a psychotic
      relative.

PMID- 8524192
TI  - [The role of the general practitioner in the prevention and control of modern
      diseases].

PMID- 8524193
TI  - [Chemotaxis activity of neutrophils and monocytes in patients with psoriasis
      vulgaris in relation to PUVA therapy].
AB  - With regard to the existing possibility favored by many immunologists that study
      on neutrophil (N) and monocyte (Mo) may throw light on the pathogenetic mechanism
      of clinical conditions such as psoriasis, the effect of PUVA therapy on human N
      and Mo chemotaxis in psoriasis vulgaris (PV) was investigated. One hundred
      psoriatic patients with severe clinical picture participated in this study: 20
      with acute exanthematic form, 16 with chronic stable form and 64 patients in
      acute flare of the chronic course. Eitzman's modified method introduced
      originally by Rebuck was employed prior to and after PUVA, to assess N and Mo
      chemotaxis. The obtained results have shown pronounced and significant
      enhancement of N and Mo migration prior to and after PUVA in all investigated
      groups of patients. Significant difference due to PUVA therapy was seen only in
      the third phase of the inflammatory response regarding all assessed patients and
      group A. In this phase, these patients showed significant decrease in N and Mo
      mobility rate after PUVA treatment in comparison to the chemotactic activity
      prior to PUVA. These findings suggest the study on N and Mo chemotaxis to be
      justified only during the third phase of the inflammatory response, when the
      assessment of PUVA effect is concerned.

PMID- 8524194
TI  - [Echocardiographic evaluation of left ventricular function in patients with
      arterial hypertension and normal left ventricular mass index].
AB  - Data about disturbances of the diastolic function of the left ventricle (LV) are
      well known in literature and registered even in the limited form of hypertension
      i.e. before the occurrence of myocardial hypertrophy. The aim of this work was to
      check this hypothesis in patients with arterial hypertension and normal LV mass
      index. The total number of examined patients was 144. The control group consisted
      of 30 patients, while the number of hypertensive patients in the other group was
      114. The following parameters were observed: blood pressure, heart rate, systolic
      and diastolic dimensions of LV, wall thickness, left ventricular mass index, wall
      stress, endsystolic and enddiastolic volume index, cardiac index, ejection
      fraction, shortening fraction, velocity peak of early and late diastolic filling
      and their mutual relationship, integral of speed-time of early and late diastolic
      pressure, as well as the index of early and late filling. A significant
      difference was found in the size of LV mass index, wall stress, velocity peak of
      early diastolic filling and the relationship of velocity peak of early and late
      filling. It should be noted that the values of the observed parameters were in
      normal ranges, but those in the group of hypertensive patients were closer to
      pathological values. CONCLUSION: Microstructural changes of LV myocard mass can
      be registered in hypertensive patients before the significant enlargement of LV
      mass index. Diastolic disfunction of the left ventricle precedes myocardial
      hypertrophy.

PMID- 8524195
TI  - [Serum lipids in surgical and natural postmenopause].
AB  - Values of serum lipids in women of different estrogenic status were analyzed in
      this paper. A deficit of estrogen was established in groups of surgically induced
      and natural postmenopausal women, but a relatively preserved production of
      estrogenic hormones in the group of women with preserved ovaries and group of
      premenopausal women. Serum triglycerides, the total serum cholesterol and LDL
      fraction of cholesterol were highest in surgically induced premenopausal women,
      somewhat lower in natural postmenopausal women, while they were statistically
      significantly lower in premenopausal women and women with preserved ovaries.
      Values of HDL cholesterol did not statistically significantly differ in certain
      groups of women. Index of atherosclerosis (IA) was highest in surgically induced
      postmenopausal women (3.18), somewhat lower in natural postmenopausal women
      (2.99) and premenopausal women (2.64), while it was statistically significantly
      lower in women with preserved ovaries (2.57).

PMID- 8524196
TI  - [Thyroid function and menopausal status in benign and malignant breast diseases].
AB  - Thyroid function was evaluated in premenopausal (healthy controls n = 7, benign
      breast disease n = 59, primary breast cancer n = 7) and postmenopausal (healthy
      controls n = 8, benign breast disease n = 51, primary breast cancer n = 10)
      groups of female subjects. The following parameters were measured: T3, T4, FT3I,
      FT3I, T3U and TSH. Except significantly higher concentration of T3 in
      postmenopausal healthy controls (179.6 +/- 32.9 vs. 152.3 +/- 22.4 p < 0.05), in
      benign and malignant breast lesions there was not any significant deviation. T3U,
      FT3I and FT4I did not significantly differ in relation to menopausal status.
      Basal TSH level was premenopausally higher in all groups, but with statistically
      significant difference within the group of primary breast cancer (0.98 +/- 0.22
      vs. 0.47 +/- 0.17 p < 0.05). Consequently, pathologic variations of thyroid
      hormones plasma level together with the changes of activities of thyrotropin
      cells could be a significant factor in premenopausal mammary tumorigenesis, while
      in benign breast lesions a possible relation between thyroid hormone instability
      and menopausal status was not identified.

PMID- 8524197
TI  - [The ischemic diabetic foot].
AB  - Among chronic complications of diabetes mellitus, the so-called diabetic foot is
      one of the most frequent causes of hospitalization. This paper is a report on
      contemporary data on etiopathogenesis, clinical features and diagnostics of
      angiopathic disorders causing diabetic foot. Special attention must be paid to
      initial lesions causing processes on subendothelial structures. Apart from well
      known risk factors causing ischemic ulcerations, increased values of Lp(a) are
      significant, as well as the decreased values of HDL cholesterol. Knowing causes
      of this disorder enables early detection of high-risk patients. Efficient
      identification and education of diabetics may stop large amputation in up to 50%
      of cases.

PMID- 8524198
TI  - [The JUS ISO 9000 Quality Control System. General requirements for laboratory
      accreditation].

PMID- 8524199
TI  - [Ischemic heart disease in young women. Its importance and possibilities of
      prevention].
AB  - Ischemic heart disease in young women is a rare disease, but nowadays it is more
      frequently detected. The investigation involved 83 women up to the age of 19 with
      ischemic heart disease. The most frequent risk factors were as follows:
      hypertension, hyperlipoproteinaemia, smoking, stress and obesity. The association
      of three factors was most often observed. Electrocardiogram at rest pointed to
      the changes as follows: anteroseptal region, the whole anterior wall, postero
      inferior region and subendocardial localization. Out of 11 exercise tests 36
      (81.81%) of them were positive. Coronary arteriography was performed in 72
      (86.71%), with positive changes in 61 (81.72%) patients. Occlusive changes were
      most frequently found on anterior descendent artery. Since a great number of risk
      factors in women may be easily corrected by an adequate diet and healthier way of
      life, their detection and implementation of measures of primary and secondary
      prevention have been attached a great importance.

PMID- 8524200
TI  - [Bacterial meningitis with a low leukocyte count at the beginning of hospital
      treatment].
AB  - The clinical pictures and the course of bacterial meningitides in 7 patients with
      leukocytes in the peripheral blood below 6.0 x 10(9)/l was examined out of 7
      patients 6 were female and 1 male, from 7 months to 56 years of age, the mean age
      X = 22.3 years. At the beginning of the hospital treatment, patients from this
      group were more frequently afebrile or subfebrile (5 patients) meningitic signs
      significant (4 patients). Parameters of nonspecific inflammatory response in
      blood, SE and fibrinogenaemia were less expressed, while the response in liquor
      to bacterial infection was normal. Gram-negative bacteria were more frequently
      isolated among etiologically established causes of meningitides. In patients with
      leukocytes below 6.0 x 10(9)/l, purulent meningitides were more often serious and
      very serious diseases (4). There were no complications in some patients and 5
      patients were completely cured (71.42%), while in 2 patients (28.58%) there was a
      mild hyperproteinorrachia in the liquor at the time of leaving hospital.

PMID- 8524201
TI  - [A double-blind, placebo-controlled study on the efficacy of Rinasek in
      symptomatic treatment of seasonal and non-seasonal rhinitis].
AB  - In order to assess the efficacy of Rinasek in symptomatic treatment of seasonal
      and nonseasonal rhinitis, 40 ambulatory otorhinolaryngologic patients were
      multicentrically examined in a placebo controlled double-blind study. Clinical
      and other findings show that the drug worked excellent in 46.6%, well in 13.3%,
      weak in 13.3% and in 10% of patients it had no effects. Consequently, Rinasek
      worked positively in 73.2%, and that is the best reason to recommend its
      application.

PMID- 8524202
TI  - [Diagnosis of solitary thyroid gland nodules].
AB  - Solitary thyroid gland nodes have presented an entity in thyroid surgery and
      endocrinology for a long period of years mostly due to frequent occurrence of
      malignomas and other changes of thyroid gland as well as to insufficient and
      uncertain clinical diagnostics. The only certain diagnostics is still the
      intraoperative exploration and ex tempore biopsy of the change, which means that
      surgery presents both a diagnostic and therapeutic procedure. At the Clinical
      Hospital Center "Dr Dragisa Milosevic" in Belgrade, Department of Surgery, 100
      patients with preoperatively diagnosed solitary thyroid gland nodes underwent
      surgery during a 4 year period. In all patients a uniform clinical diagnostics
      was performed, and then, on the basis of intraoperative findings and ex tempore
      biopsy, gathered results were compared and reliability of certain preoperative
      diagnostic procedures was considered in regard to intraoperative findings. The
      aim of this study was to point to necessity of application of all relevant
      indexes in diagnostics with a special review on the intraoperative finding as the
      most relevant in making the decision about the range of surgery and further
      postoperative treatment.

PMID- 8524203
TI  - [Pelvic inflammatory disease and the use of intrauterine contraceptive devices].
AB  - Pelvic inflammatory disease includes a group of different diseases such as:
      endometritis, salpingitis, oophoritis and peritonitis. The risk of pelvic
      inflammatory disease in intrauterine contraceptive devices--users is 7-9 times
      higher than in the general population, whereas the incidence of occurrence of
      these diseases in this certain group is 2-5%. During the period 1989-1993, 155
      intrauterine contraceptive users with pelvic inflammatory disease, were treated
      at the Clinic, which makes 25% of all hospitalized female patients with pelvic
      inflammatory disease. Serious cases have been established in regard to the period
      10 years ago. In order to prevent the occurrence of pelvic inflammatory disease
      in users of intrauterine contraceptive devices, health education is necessary to
      motivate regular controls and check-ups, preventive application of antiseptic
      vaginal tablets and detection of signs of the disease.

PMID- 8524204
TI  - [Literature cited in a study of Yugoslav biomedical journals].
AB  - The paper reviews results of a research on literature cited in papers published
      in two most remarkable Yugoslav biomedical journals, Medicinski Pregled and
      Srpski arhiv za celokupno lekarstvo, in 1985 and 1992. The analysis included the
      following parameters: the amount of published papers, the quantity of cites out
      of the literature that has been used, frequency of citation of foreign and
      domestic literature as well as the quantity of self citations. According to the
      gathered results, foreign literature is remarkably more often cited than the
      domestic references, mostly in English, but the percentage of citing one's own
      papers is also high.

PMID- 8524205
TI  - [Suicide by starvation].
AB  - Authors report about an extraordinary suicide with fasting, rejecting food and
      hard persistence considering the accomplishment of the goal. Although suicide is
      the final result of numerous social disorders and diseases, this case report must
      be dissociated from the domain of psychiatry. The motive for such a suicide was a
      great emotional loss, isolation and social abandonment, suggesting an unenviable
      quality of life in future. We can agree that in such a position one has a right
      and free will to make a decision about ending one's life. In that context we have
      accepted the failure of all taken measures in treatment and attempts to prevent
      suicide. Apart from our standpoint, we must ask several questions: could the
      person committing suicide be saved, was everything possible done to save him, was
      psychiatric ability or inability the reason which accelerated suicide?

PMID- 8524206
TI  - [The Spanish influenza pandemic in Sajkaska 1918-1919].
AB  - In this paper the author presents the frequency of death caused by Spanish
      influenza from 1918-1919 in 15 villages of Sajkaska according to sex and age. He
      established that it included all Sajkaska and that it killed numerous persons of
      all age groups. The greatest mortality from Spanish influenza was in Nadalj in
      which the total number of deceased was 60, and the number of those who died from
      Spanish influenza was 31 or 51.67%.

PMID- 8524207
TI  - [Nuclear magnetic resonance spectroscopy: methodology and applications to the
      study of asphyxia neonatorum].
AB  - Cerebral metabolism has been extensively studied by magnetic resonance
      spectroscopy (MRS). MRS allows the study of neonates brain maturation as well as
      the onset and the evolution of brain injury. The use of phosphorous spectroscopy
      allows the quantification of phosphorylated metabolites. Thus, the measurement of
      the relative concentrations of creatine-phosphate and inorganic-phosphate is a
      prognostic factor of the outcome of a neonate after birth asphyxia. Absolute
      concentrations have more recently been studied and seem to be more significant.
      Proton MRS gives access to brain metabolites such as choline, lactate, N-acetyl
      aspartate and taurine. Its use is more recent than the phosphorous spectroscopy
      but first results already show its potential in neonatology.

PMID- 8524208
TI  - [Cognitive evoked potentials in children: normal and abnormal development].
AB  - The first part of this review on event-related potentials (ERPs) in children
      summarizes the role of ERPs in the study of normal cognitive development. The
      ERPs vary both as a function of the age of the child and also as a function of
      the cognitive processes that are required by the tasks. Topographical studies
      allow one to identify cortical regions involved in specific cognitive processes,
      and monitor their age-related changes. The second part of this paper reviews two
      examples of abnormal cognitive development (attention deficit hyperactivity
      disorder and childhood autism) where the ERPs allow a better understanding of the
      dysfunction underlying the observed cognitive disorders.

PMID- 8524209
TI  - Prognostic significance of electrophysiological investigations in stroke
      patients: somatosensory and motor evoked potentials and sympathetic skin
      response.
AB  - A prospective 3-month follow-up examination was carried out in 12 patients with
      supratentorial stroke. Motor evoked potentials (MEP), somatosensory evoked
      potentials (SEP) and sympathetic skin responses (SSR) were performed 1-7 days, 30
      days and 3 months after stroke. The functional outcome measured by a daily
      activity index (Barthel index) was assessed 3 months after the stroke. There was
      a significant correlation between SEP and MEP results obtained for the first week
      and recovery of sensation and motility 3 months later. When initially normal,
      motor potentials evoked by transcranial magnetic stimulation had a significant
      predictive value for long-term functional outcome, whereas SEP and SSR did not.
      SSR present at the initial stage was correlated with the state of consciousness.

PMID- 8524210
TI  - Epilepsia partialis continua in a case of MELAS: clinical and neurophysiological
      study.
AB  - There are few reports in the literature dealing with the association between
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS) and epilepsia partialis continua (EPC) in children. We report the case of
      a child presenting with numerous stroke-like episodes associated with EPC which,
      despite therapy, were not controlled and aggravated the clinical condition of our
      patient. We present the neuroradiological, biochemical, genetic and muscle biopsy
      findings, and EEG characteristics, with attention to polygraphic recordings which
      were done during wake and sleep periods. We consider the correlation with other
      possible etiological factors relating to EPC and in particular coinvolvement of
      the basal ganglia as a cause of EPC in our patient.

PMID- 8524211
TI  - [Electrophysiologic tests and benzodiazepine hypnosis].
AB  - The effects of a pure benzodiazepine antagonist (Flumazenil) on the responses R1
      and R2 of the blink reflex, psychomotor tests, and Event Related Potentials
      (ERP), in six healthy volunteers sedated with Midazolam have been compared.
      Measurements were made during each of four successive phases. Phase 0
      corresponded to control recordings. Midazolam was administered rapidly during
      phase 1 and slowly during phase 2. Phase 3 corresponded to spontaneous waking
      once the administration of Midazolam had been stopped. Flumazenil was
      administered during phase 2. As the subjects fell asleep, R1 and R2 were the last
      parameters to disappear. Under the influence of Flumazenil, R1 was the first to
      reappear, while R2 did not recur until complete waking, and the other tests were
      unpracticable. During phase 3, R1 reappeared before R2 once more, the psychomotor
      test responses and ERP returning only later. The modifications of both R1 and R2
      of the blink reflex are a good criterion of the presence of BZD in a toxic coma
      and a good test to indicate the depth of a coma or a sedation with BZD, whilst
      ERP, since they require the cooperation of the patient, are a test of vigilance
      and not of awakening.

PMID- 8524212
TI  - Synergistic activation of retinoic acid (RA)-responsive genes and induction of
      embryonal carcinoma cell differentiation by an RA receptor alpha (RAR alpha)-,
      RAR beta-, or RAR gamma-selective ligand in combination with a retinoid X
      receptor-specific ligand.
AB  - Retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers bind to
      cognate response elements in vitro more efficiently than do RAR or RXR
      homodimers, and both RAR and RXR partners have been shown to activate various
      promoters in transiently transfected cells. We have now investigated whether
      ligand-dependent activation of both heterodimeric partners is involved in induced
      expression of endogenous RA-responsive genes and in P19 and F9 cell
      differentiation. On their own, low concentrations of retinoids selective for
      either RAR alpha, RAR beta, or RAR gamma did not induce or very inefficiently
      induced the expression of several RA target genes or triggered differentiation.
      An RXR-specific synthetic retinoid was similarly inefficient at any
      concentration. In contrast, at the same concentrations, various combinations of
      RAR (RAR alpha, RAR beta, or RAR gamma) and RXR selective retinoids resulted in
      synergistic induction of all retinoic acid (RA) target genes examined, as well as
      in cell differentiation. However, the magnitude of this synergistic activation
      varied depending on both the RAR-RXR combination and the promoter context of the
      responsive genes. Promiscuous activation of the three RARs, or concomitant
      activation of RAR alpha and RAR gamma, at selective retinoid concentrations also
      resulted in induction of gene expression and cell differentiation. Taken
      together, our results are consistent with the conclusion that the RAR and RXR
      partners of RAR-RXR heterodimers can synergistically activate transcription of RA
      responsive genes and can induce differentiation of P19 and F9 cells. Our results
      also indicate that there is a significant degree of functional redundancy between
      the three RAR types which, however, varies with the nature of the RA target
      genes.

PMID- 8524213
TI  - DNA rearrangements in Euplotes crassus coincide with discrete periods of DNA
      replication during the polytene chromosome stage of macronuclear development.
AB  - Macronuclear development in Euplotes crassus begins with polytenization of
      micronuclear chromosomes and is accompanied by highly precise excision of DNA
      sequences known as internal eliminated sequences and transposon-like elements
      (Tecs). Quantitation of radiolabeled-precursor incorporation into DNA indicates
      that DNA synthesis during formation of polytene chromosomes is not continuous and
      occurs during two distinct periods. We demonstrate that the timing of Tec
      excision coincides with these replication periods and that excision can occur
      during both periods even at a single locus. We also show that Tec and internal
      eliminated sequence excisions are coincident in the second replication period,
      thus providing further evidence for similarity in their excision mechanism.
      Inhibition of DNA synthesis with hydroxyurea diminishes Tec element excision,
      indicating that replication is an important aspect of the excision process.

PMID- 8524214
TI  - Neu differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and
      displays a differential requirement for ErbB-2.
AB  - Neu differentiation factor (NDF)-induced signaling involves the activation of
      members of the ErbB family of receptor tyrosine kinases. Although ectopic
      expression of recombinant ErbB receptors has yielded valuable insight into their
      signaling properties, the biological function and in vivo interplay of these
      receptors are still poorly understood. We addressed this issue by studying NDF
      signaling in various human cell lines expressing moderate levels of all known
      ErbB receptors. NDF-induced phosphorylation of ErbB-2 and ErbB-3 was found in the
      breast epithelial cell line MCF10A, the breast tumor cell lines T47D and MCF7,
      and the ovarian tumor cell line OVCAR3. Despite similar expression levels, NDF
      induced phosphorylation of ErbB-4 was cell specific and only detected in T47D and
      OVCAR3 cells. Blocking cell surface expression of ErbB-2 by intracellular
      expression of a single-chain antibody revealed that in these two cell lines, ErbB
      2 significantly enhanced phosphorylation of ErbB-4. Efficient NDF-induced
      phosphorylation of ErbB-3 was strictly ErbB-2 dependent in the breast tumor cell
      lines T47D and MCF7, while it was largely ErbB-2 independent in MCF10A and OVCAR3
      cells. Consequently, NDF-stimulated intracellular signaling and induction of a
      biological response displayed a cell-specific requirement for ErbB-2. Thus, while
      ErbB-2 cooperates with NDF receptors in the breast tumor cell lines, ErbB-2
      independent mechanisms seem to prevail in other cellular contexts.

PMID- 8524215
TI  - Association of the viral oncoprotein STP-C488 with cellular ras.
AB  - The STP-C488 oncogene of herpesvirus saimiri has transforming activity
      independent of the rest of the viral genome. We now demonstrate that STP-C488
      associates with cellular ras in transformed cells. Mutations that disrupted this
      association with ras disrupted the transforming ability of the STP-C488 oncogene.
      Binding assays showed that STP-C488 was capable of competing with raf-1 for
      binding to ras. Expression of STP-C488 activated the ras signaling pathway as
      evidenced by a two- to fourfold increase in the ratio of ras-GTP to ras-GDP and
      by the constitutive activation of mitogen-activated protein kinase. Consistent
      with an activation of signaling through ras, STP-C488 expression induced ras
      dependent neurite outgrowth in PC12 cells. STP-C488 is the first virus-encoded
      protein shown to achieve oncogenic transformation via association with cellular
      ras.

PMID- 8524216
TI  - Ornithine decarboxylase- and ras-induced cell transformations: reversal by
      protein tyrosine kinase inhibitors and role of pp130CAS.
AB  - We have found that overexpression of human ornithine decarboxylase (ODC) induces
      cell transformation in NIH 3T3 and Rat-1 cells (M. Auvinen, A. Paasinen, L. C.
      Andersson, and E. Holtta, Nature (London) 360:355-358, 1992). The ODC-transformed
      cells display increased levels of tyrosine phosphorylation, in particular of a
      cluster of 130-kDa proteins. Here we show that one of the proteins with enhanced
      levels of tyrosine phosphorylation in ODC-overexpressing cells is the previously
      described p130 substrate of pp60v-src, known to associate also with v-Crk and
      designated p130CAS. We also studied the role of protein tyrosine phosphorylation
      in the ODC-induced cell transformation by exposing the cells to herbimycin A, a
      potent inhibitor of Src-family kinases, and to other inhibitors of protein
      tyrosine kinases. Treatment with the inhibitors reversed the phenotype of ODC
      transformed cells to normal, with an organized, filamentous actin cytoskeleton.
      Coincidentally, the tyrosine hyperphosphorylation of p130 was markedly reduced,
      while the level of activity of ODC remained highly elevated. A similar reduction
      in pp130 phosphorylation and reversion of morphology by herbimycin A were
      observed in v-src- and c-Ha-ras-transformed cells. In addition, we show that
      expression of antisense mRNA for p130CAS resulted in reversion of the transformed
      phenotype of all these cell lines. An increased level of tyrosine kinase
      activity, not caused by c-Src or c-Abl, was further detected in the cytoplasmic
      fraction of ODC-transformed cells. Preliminary characteristics of this kinase are
      shown. These data indicate that p130CAS is involved in cell transformation by
      ODC, c-ras, and v-src oncogenes, raise the intriguing possibility that p130CAS
      may be generally required for transformation, and imply that there is at least
      one protein tyrosine kinase downstream of ODC that is instrumental for cell
      transformation.

PMID- 8524217
TI  - Met30p, a yeast transcriptional inhibitor that responds to S-adenosylmethionine,
      is an essential protein with WD40 repeats.
AB  - A specific repression mechanism regulates the biosynthesis of sulfur amino acids
      in Saccharomyces cerevisiae. When the intracellular S-adenosylmethionine (AdoMet)
      concentration increases, transcription of the sulfur genes is repressed. Using a
      specific reporter system, we have isolated mutations impairing the AdoMet
      mediated transcriptional regulation of the sulfur network. These mutations
      identified a new gene, MET30, and were shown to also affect the regulation of the
      methyl cycle. The MET30 gene was isolated and sequenced. Sequence analysis
      reveals that Met30p contains five copies of the WD40 motif within its carboxy
      terminal part, like the yeast transcriptional repressors Hir1p and Tup1p. We
      identified one target of Met30p as Met4p, a transcriptional activator regulating
      the sulfate assimilation pathway. By the two-hybrid method, we showed that Met30p
      interacts with Met4p and identified a region of Met4p involved in this
      interaction. Further analysis reveals that expression of Met30p is essential for
      cell viability.

PMID- 8524218
TI  - v-Abl activates c-myc transcription through the E2F site.
AB  - The v-abl oncogene of Abelson murine leukemia virus encodes a deregulated form of
      the cellular nonreceptor tyrosine kinase. v-Abl activates c-myc transcription,
      and c-Myc is an essential downstream component in the v-Abl transformation
      program. To explore the mechanism by which v-Abl activates c-myc transcription, a
      cotransfection assay was developed. We show that transactivation of a c-myc
      promoter by v-Abl requires the SH1 (tyrosine kinase) and SH2 domains of v-Abl;
      the C-terminal domains are not required for transactivation. The assay also
      identified the E2F site in the c-myc promoter as a v-Abl-responsive element. In
      addition, multimerized E2F sites were shown to be sufficient to confer v-Abl
      dependent activation on a minimal promoter. This is the first identification of a
      v-Abl response element for transcriptional activation. v-Abl tyrosine kinase
      dependent changes in proteins binding the c-myc E2F site were also demonstrated,
      including induction of a complex containing DP1, p107, cyclin A, and cdk2.
      Identification of v-Abl-dependent changes in E2F-binding proteins provides an
      important link between v-Abl, transcription, cell cycle regulation, and control
      of cellular growth.

PMID- 8524219
TI  - Yeast MEK-dependent signal transduction: response thresholds and parameters
      affecting fidelity.
AB  - Ste7p and Mkk1p are MEK (MAPK/ERK kinase) family members that function in the
      mating and cell integrity signal transduction pathways in Saccharomyces
      cerevisiae. We selected STE7 and MKK1 mutations that stimulated their respective
      pathways in the absence of an inductive signal. Strikingly, serine-to-proline
      substitutions at analogous positions in Ste7p (position 368) and Mkk1p (position
      386) were recovered by independent genetic screens. Such an outcome suggests that
      this substitution in other MEKs would exhibit similar properties. The Ste7p-P368
      variant has higher basal enzymatic activity than Ste7p but still requires
      induction to reach full activation. The higher activity associated with Ste7p
      P368 allows it to compensate for defects in the cell integrity pathway, but it
      does so only when it is overproduced or when Ste5p is missing. This behavior
      suggests that Ste5p, which has been proposed to be a tether for the kinases in
      the mating pathway, contributes to Ste7p specificity.

PMID- 8524220
TI  - p53 inhibits DNA replication in vitro in a DNA-binding-dependent manner.
AB  - The p53 tumor suppressor gene product is a sequence-specific DNA-binding protein
      that is necessary for the G1 arrest of many cell types. Consistent with its role
      as a cell cycle checkpoint factor, p53 has been shown to be capable of both
      transcriptional activation and repression. Here we show a new potential role for
      p53 as a DNA-binding-dependent regulator of DNA replication. Constructs
      containing multiple copies of the ribosomal gene cluster (RGC) p53 binding site
      cloned on the late side of the polyomavirus origin were used in in vitro
      replication assays. In the presence of p53, the replication of these constructs
      was strongly inhibited, while the replication of constructs containing a mutant
      version of the RGC site was not affected by p53. Several tumor-derived mutant p53
      proteins were unable to inhibit replication of the construct with wild-type RGC
      sites. Additionally, the transactivator GAL4-VP16 was unable to inhibit
      replication of a construct containing GAL4 binding sites adjacent to the
      polyomavirus origin. We also show that the inhibition by p53 can occur from sites
      cloned as far as 600 bp from the origin. Preincubation experiments suggest that
      p53 inhibits replication at a step mediated by ATP, possibly by inhibiting the
      binding of polyomavirus T antigen to the core origin. The presence of an
      endogenous p53 binding site in the polyomavirus origin suggests potential
      mechanisms for the observed inhibition.

PMID- 8524221
TI  - Ubiquitous and neuronal DNA-binding proteins interact with a negative regulatory
      element of the human hypoxanthine phosphoribosyltransferase gene.
AB  - The hypoxanthine phosphoribosyltransferase (HPRT) gene is constitutively
      expressed at low levels in all tissues but at higher levels in the brain; the
      significance and mechanism of this differential expression are unknown. We
      previously identified a 182-bp element (hHPRT-NE) within the 5'-flanking region
      of the human HPRT (hHPRT) gene, which is involved not only in conferring neuronal
      specificity but also in repressing gene expression in nonneuronal tissues. Here
      we report that this element interacts with different nuclear proteins, some of
      which are present specifically in neuronal cells (complex I) and others of which
      are present in cells showing constitutive expression of the gene (complex II). In
      addition, we found that complex I factors are expressed in human NT2/D1 cells
      following induction of neuronal differentiation by retinoic acid. This finding
      correlates with an increase of HPRT gene transcription following neuronal
      differentiation. We also mapped the binding sites for both complexes to a 60-bp
      region (Ff; positions -510 to -451) which, when analyzed in transfection assays,
      functioned as a repressor element analogous to the full-length hHPRT-NE sequence.
      Methylation interference footprintings revealed a minimal unique DNA motif, 5'
      GGAAGCC-3', as the binding site for nuclear proteins from both neuronal and
      nonneuronal sources. However, site-directed mutagenesis of the footprinted region
      indicated that different nucleotides are essential for the associations of these
      two complexes. Moreover, UV cross-linking experiments showed that both complexes
      are formed by the association of several different proteins. Taken together,
      these data suggest that differential interaction of DNA-binding factors with this
      regulatory element plays a crucial role in the brain-preferential expression of
      the gene, and they should lead to the isolation of transcriptional regulators
      important in neuronal expression of the HPRT gene.

PMID- 8524222
TI  - NDT80, a meiosis-specific gene required for exit from pachytene in Saccharomyces
      cerevisiae.
AB  - We describe the identification of a new meiosis-specific gene of Saccharomyces
      cerevisiae, NDT80. The ndt80 null and point mutants arrest at the pachytene stage
      of meiosis, with homologs connected by full-length synaptonemal complexes and
      spindle pole bodies duplicated but unseparated. Meiotic recombination in an ndt80
      delta mutant is relatively normal, although commitment to heteroallelic
      recombination is elevated two- to threefold and crossing over is decreased
      twofold compared with those of the wild type. ndt80 arrest is not alleviated by
      mutations in early recombination genes, e.g., SPO11 or RAD50, and thus cannot be
      attributed to an intermediate block in prophase chromosome metabolism like that
      observed in several other mutants. The ndt80 mutant phenotype during meiosis most
      closely resembles that of a cdc28 mutant, which contains a thermolabile p34, the
      catalytic subunit of maturation-promoting factor. Cloning and molecular analysis
      reveal that the NDT80 gene maps on the right arm of chromosome VIII between EPT1
      and a Phe-tRNA gene, encodes a 627-amino-acid protein which exhibits no
      significant homology to other known proteins, and is transcribed specifically
      during middle meiotic prophase. The NDT80 gene product could be a component of
      the cell cycle regulatory machinery involved in the transition out of pachytene,
      a participant in an unknown aspect of meiosis sensed by a pachytene checkpoint,
      or a SPO11- and RAD50-independent component of meiotic chromosomes that is the
      target of cell cycle signaling.

PMID- 8524223
TI  - Mitogenic signals and transforming potential of Nyk, a newly identified neural
      cell adhesion molecule-related receptor tyrosine kinase.
AB  - Nyk/Mer is a recently identified receptor tyrosine kinase with neural cell
      adhesion molecule-like structure (two immunoglobulin G-like domains and two
      fibronectin III-like domains) in its extracellular region and belongs to the
      Ufo/Axl family of receptors. The ligand for Nyk/Mer is presently unknown, as are
      the signal transduction pathways mediated by this receptor. We constructed and
      expressed a chimeric receptor (Fms-Nyk) composed of the extracellular domain of
      the human colony-stimulating factor 1 receptor (Fms) and the transmembrane and
      cytoplasmic domains of human Nyk/Mer in NIH 3T3 fibroblasts in order to
      investigate the mitogenic signaling and biochemical properties of Nyk/Mer. Colony
      stimulating factor 1 stimulation of the Fms-Nyk chimeric receptor in transfected
      NIH 3T3 fibroblasts leads to a transformed phenotype and generates a
      proliferative response in the absence of other growth factors. We show that
      phospholipase C gamma, phosphatidylinositol 3-kinase/p70 S6 kinase, Shc, Grb2,
      Raf-1, and mitogen-activated protein kinase are downstream components of the
      Nyk/Mer signal transduction pathways. In addition, Nyk/Mer weakly activates
      p90rsk, while stress-activated protein kinase, Ras GTPase-activating protein
      (GAP), and GAP-associated p62 and p190 proteins are not activated or tyrosine
      phosphorylated by Nyk/Mer. An analysis comparing the Nyk/Mer signal cascade with
      that of the epidermal growth factor receptor indicates substrate preferences by
      these two receptors. Our results provide a detailed description of the Nyk/Mer
      signaling pathways. Given the structural similarity between the Ufo/Axl family
      receptors, some of the information may also be applied to other members of this
      receptor tyrosine kinase family.

PMID- 8524224
TI  - Context effects on misreading and suppression at UAG codons in human cells.
AB  - The effect of the 3' codon context on the efficiency of nonsense suppression in
      mammalian tissue culture cells has been tested. Measurements were made following
      the transfection of cells with a pRSVgal reporter vector that contained the
      classical Escherichia coli lacZ UAG allele YA559. The position of this mutation
      was mapped by virtue of its fortuitous creation of a CTAG MaeI restriction enzyme
      site. Determination of the local DNA sequence revealed a C-->T mutation at codon
      600 of the lacZ gene: CAG-->TAG. Site-directed mutagenesis was used to create a
      series of vectors in which the base 3' to the nonsense codon was either A, C, G,
      or U. Suppression of the amber-containing reporter was achieved by cotransfection
      with genes for human tRNA(Ser) or tRNA(Gln) UAG nonsense suppressors and by
      growth in the translational error-promoting aminoglycoside drug G418. Nonsense
      suppression was studied in the human cell lines 293 and MRC5V1 and the simian
      line COS-7. Overall, the rank order for the effect of changes to the base 3' to
      UAG was C < G = U < A. This study confirms and extends earlier findings that in
      mammalian cells 3' C supports efficient nonsense suppression while 3' A is
      unsympathetic for read-through at nonsense codons. The rules for the mammalian
      codon context effect on nonsense suppression are therefore demonstrably different
      from those in E. coli.

PMID- 8524225
TI  - Functional reconstruction of trans regulation of the Ultrabithorax promoter by
      the products of two antagonistic genes, trithorax and Polycomb.
AB  - Maintenance of the "on-off" state of Drosophila homeotic genes in Antennapedia
      and bithorax complexes requires activities of the trithorax and Polycomb groups
      of genes. To identify cis-acting sequences for functional reconstruction of
      regulation by both trithorax and Polycomb, we examined the expression patterns of
      several Ubx-lacZ transgenes that carry upstream fragments corresponding to a
      region of approximately 50 kb. A 14.5-kb fragment from the
      postbithorax/bithoraxoid region of Ultrabithorax exhibited proper regulation by
      both trithorax and Polycomb in the embryonic central nervous system. Using a
      Drosophila haploid cell line for transient expression, we found that trithorax or
      Polycomb can function independently through this upstream fragment to activate or
      repress the Ultrabithorax promoter, respectively. Studies of deletion mutants of
      trithorax and Polycomb demonstrated that trithorax-dependent activation requires
      the central zinc-binding domain, while Polycomb-dependent repression requires the
      intact chromodomain. In addition, trithorax-dependent activity can be abrogated
      by increasing the amount of Polycomb, suggesting a competitive interaction
      between the products of trithorax and Polycomb. Deletion analysis of this
      fragment demonstrated that a 440-bp fragment contains response elements for both
      trithorax and Polycomb. Furthermore, we showed that the integrity of the proximal
      promoter region is essential for trithorax-dependent activation, implicating a
      long-range interaction for promoter activation.

PMID- 8524227
TI  - The human topoisomerase I gene promoter is regulated by NF-IL6.
AB  - We investigated the expression of the human DNA topoisomerase I (hTOP1) gene in
      HeLa cells and in adenovirus-transformed 293 cells. A highly conserved proximal
      promoter element is essential for hTOP1 promoter activity in HeLa cells but not
      in 293 cells. This correlates with the presence of specific promoter-binding
      proteins in HeLa cells and their absence in 293 cells. We identified the HeLa
      binding protein by screening a cDNA expression library with the specific promoter
      site as a probe and demonstrate now that the activating protein is identical to
      the nuclear factor for interleukin-6 expression (NF-IL6), a member of the C/EBP
      family of transcription factors. Overexpression of NF-IL6 strongly stimulates
      hTOP1 promoter activity in HeLa cells, suggesting that NF-IL6 is a major hTOP1
      regulating protein. Because of the presence of adenovirus protein E1A, 293 cells
      express the hTOP1 gene more efficiently than HeLa cells but do not contain NF-IL6
      activity. E1A activation of the hTOP1 promoter is suppressed by NF-IL6
      overexpression. This result supports previous observations concerning a
      functional interaction between viral protein E1A and NF-IL6. Finally, we show
      that hTOP1 gene expression in differentiating macrophages is correlated with the
      synthesis of NF-IL6-specific mRNA.

PMID- 8524226
TI  - Evidence that farnesyltransferase inhibitors suppress Ras transformation by
      interfering with Rho activity.
AB  - Small-molecule inhibitors of the housekeeping enzyme farnesyltransferase (FT)
      suppress the malignant growth of Ras-transformed cells. Previous work suggested
      that the activity of these compounds reflected effects on actin stress fiber
      regulation rather than Ras inhibition. Rho proteins regulate stress fiber
      formation, and one member of this family, RhoB, is farnesylated in vivo.
      Therefore, we tested the hypothesis that interference with RhoB was the principal
      basis by which the peptidomimetic FT inhibitor L-739,749 suppressed Ras
      transformation. The half-life of RhoB was found to be approximately 2 h,
      supporting the possibility that it could be functionally depleted within the 18-h
      period required by L-739,749 to induce reversion. Cell treatment with L-739,749
      disrupted the vesicular localization of RhoB but did not effect the localization
      of the closely related RhoA protein. Ras-transformed Rat1 cells ectopically
      expressing N-myristylated forms of RhoB (Myr-rhoB), whose vesicular localization
      was unaffected by L-739,749, were resistant to drug treatment. The protective
      effect of Myr-rhoB required the integrity of the RhoB effector domain and was not
      due to a gain-of-function effect of myristylation on cell growth. In contrast,
      Rat1 cells transformed by a myristylated Ras construct remained susceptible to
      growth inhibition by L-739,749. We concluded that Rho is necessary for Ras
      transformation and that FT inhibitors suppress the transformed phenotype at least
      in part by direct or indirect interference with Rho, possibly with RhoB itself.

PMID- 8524228
TI  - Requirement of the self-glucosylating initiator proteins Glg1p and Glg2p for
      glycogen accumulation in Saccharomyces cerevisiae.
AB  - Glycogen, a branched polymer of glucose, is a storage molecule whose accumulation
      is under rigorous nutritional control in many cells. We report the identification
      of two Saccharomyces cerevisiae genes, GLG1 and GLG2, whose products are
      implicated in the biogenesis of glycogen. These genes encode self-glucosylating
      proteins that in vitro can act as primers for the elongation reaction catalyzed
      by glycogen synthase. Over a region of 258 residues, the Glg proteins have 55%
      sequence identify to each other and approximately 33% identity to glycogenin, a
      mammalian protein postulated to have a role in the initiation of glycogen
      biosynthesis. Yeast cells defective in either GLG1 or GLG2 are similar to the
      wild type in their ability to accumulate glycogen. Disruption of both genes
      results in the inability of the cells to synthesize glycogen despite normal
      levels of glycogen synthase. These results suggest that a self-glucosylating
      protein is required for glycogen biosynthesis in a eukaryotic cell. The
      activation state of glycogen synthase in glg1 glg2 cells is suppressed,
      suggesting that the Glg proteins may additionally influence the phosphorylation
      state of glycogen synthase.

PMID- 8524229
TI  - Degradation of the soybean ribulose-1,5-bisphosphate carboxylase small-subunit
      mRNA, SRS4, initiates with endonucleolytic cleavage.
AB  - The degradation of the soybean SRS4 mRNA, which encodes the small subunit of
      ribulose-1,5-bisphosphate carboxylase, yields a set of proximal (5' intact) and
      distal (3' intact) products both in vivo and in vitro. These products are
      generated by endonucleolytic cleavages that occur essentially in a random order,
      although some products are produced more rapidly than others. Comparison of sizes
      of products on Northern (RNA) blots showed that the combined sizes of pairs of
      proximal and distal products form contiguous full-length SRS4 mRNAs. When the 3'
      ends of the proximal products and the 5' ends of the distal products were mapped
      by S1 nuclease and primer extension assays, respectively, both sets of ends
      mapped to the same sequences within the SRS4 mRNA. A small in vitro-synthesized
      RNA fragment containing one cleavage site inhibited cleavage of all major sites,
      equivalently consistent with one enzymatic activity generating the
      endonucleolytic cleavage products. These products were rich in GU nucleotides,
      but no obvious consensus sequence was found among several cleavage sites.
      Preliminary evidence suggested that secondary structure could play a role in site
      selection. The structures of the 5' ends of the proximal products and the 3' ends
      of the distal products were examined. Proximal products were found with
      approximately equal frequency in both m7G cap(+) and m7G cap(-) fractions,
      suggesting that the endonucleolytic cleavage events occurred independently of the
      removal of the 5' cap structure. Distal products were distributed among fractions
      with poly(A) tails ranging from undetectable to greater than 100 nucleotides in
      length, suggesting that the endonucleolytic cleavage events occurred
      independently of poly(A) tail shortening. Together, these data support a
      stochastic endonuclease model in which an endonucleolytic cleavage event is the
      initial step in SRS4 mRNA degradation.

PMID- 8524230
TI  - Cell cycle regulation of RNA polymerase III transcription.
AB  - Inactivation of the TATA-binding protein-containing complex TFIIIB contributes to
      the mitotic repression of RNA polymerase III transcription, both in frogs and in
      humans (J. M. Gottesfeld, V. J. Wolf, T. Dang, D. J. Forbes, and P. Hartl,
      Science 263:81-84, 1994; R. J. White, T. M. Gottlieb, C. S. Downes, and S. P.
      Jackson, Mol. Cell. Biol. 15:1983-1992, 1995). Using extracts of synchronized
      proliferating HeLa cells, we show that TFIIIB activity remains low during the
      early part of G1 phase and increases only gradually as cells approach S phase. As
      a result, the transcription of all class III genes tested is significantly less
      active in early G1 than it is in S or G2 phase, both in vitro and in vivo. The
      increased activity of TFIIIB as cells progress through interphase appears to be
      due to changes in the TATA-binding protein-associated components of this complex.
      The data suggest that TFIIIB is an important target for the cell cycle regulation
      of RNA polymerase III transcription during both mitosis and interphase of
      actively proliferating HeLa cells.

PMID- 8524231
TI  - Modular structure of chromosomal proteins HMG-14 and HMG-17: definition of a
      transcriptional enhancement domain distinct from the nucleosomal binding domain.
AB  - Chromosomal proteins HMG-14 and HMG-17 are the only known nuclear proteins which
      specifically bind to the nucleosome core particle and are implicated in the
      generation and/or maintenance of structural features specific to active
      chromatin. The two proteins facilitate polymerase II and III transcription from
      in vitro- and in vivo-assembled circular chromatin templates. Here we used
      deletion mutants and specific peptides to identify the transcriptional
      enhancement domain and delineate the nucleosomal binding domain of the HMG-14 and
      -17 proteins. Deletion of the 22 C-terminal amino acids of HMG-17 or 26 C
      terminal amino acids of HMG-14 reduces significantly the ability of the proteins
      to enhance transcription from chromatin templates. In contrast, N-terminal
      truncation mutants had the same transcriptional enhancement activity as the full
      length proteins. We conclude that the negatively charged C-terminal region of the
      proteins is required for transcriptional enhancement. Chromatin transcription
      enhancement assays, which involve binding competition between the full-length
      proteins and peptides derived from their nucleosomal binding regions, indicate
      that the minimal nucleosomal binding domain of human HMG-17 is 24 amino acids
      long and spans residues 17 to 40. The results suggest that HMG-14 and -17
      proteins have a modular structure and contain distinct functional domains.

PMID- 8524232
TI  - Initiation binding repressor, a factor that binds to the transcription initiation
      site of the histone h5 gene, is a glycosylated member of a family of cell growth
      regulators [corrected].
AB  - Initiation binding repressor [corrected] (IBR) is a chicken erythrocyte factor
      (apparent molecular mass, 70 to 73 kDa) that binds to the sequences spanning the
      transcription initiation site of the histone h5 gene, repressing its
      transcription. A variety of other cells, including transformed erythroid
      precursors, do not have IBR but a factor referred to as IBF (68 to 70 kDa) that
      recognizes the same IBR sites. We have cloned the IBR cDNA and studied the
      relationship of IBR and IBF. IBR is a 503-amino-acid-long acidic protein which is
      99.0% identical to the recently reported human NRF-1/alpha-Pal factor and highly
      related to the invertebrate transcription factors P3A2 and erected wing gene
      product (EWG). We present evidence that IBR and IBF are most likely identical
      proteins, differing in their degree of glycosylation. We have analyzed several
      molecular aspects of IBR/F and shown that the factor associates as stable
      homodimers and that the dimer is the relevant DNA-binding species. The
      evolutionarily conserved N-terminal half of IBR/F harbors the DNA
      binding/dimerization domain (outer limits, 127 to 283), one or several casein
      kinase II sites (37 to 67), and a bipartite nuclear localization signal (89 to
      106) which appears to be necessary for nuclear targeting. Binding site selection
      revealed that the alternating RCGCRYGCGY consensus constitutes high-affinity
      IBR/F binding sites and that the direct-repeat palindrome TGCGCATGCGCA is the
      optimal site. A survey of genes potentially regulated by this family of factors
      primarily revealed genes involved in growth-related metabolism.

PMID- 8524234
TI  - M-phase-specific phosphorylation of the POU transcription factor GHF-1 by a cell
      cycle-regulated protein kinase inhibits DNA binding.
AB  - GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type
      specific transcription factor responsible for determination and expansion of
      growth hormone (GH)- and prolactin-expressing cells in the anterior pituitary. It
      was previously suggested that cyclic AMP (cAMP)-responsive protein kinase A (PKA)
      phosphorylates GHF-1 at a site within the N-terminal arm of its homeodomain,
      thereby inhibiting its binding to the GH promoter. These results, however, are
      inconsistent with the physiological stimulation of GH production by the cAMP
      pathway. As reported here, cAMP agonists and PKA do not inhibit GHF-1 activity in
      living cells and although they stimulate the phosphorylation of GHF-1, the
      inhibitory phosphoacceptor site within the homeodomain is not affected. Instead,
      this site, Thr-220, is subject to M-phase-specific phosphorylation. As a result,
      GHF-1 DNA binding activity is transiently inhibited during the M phase. This
      activity is regained once cells enter G1, a phase during which GHF-1
      phosphorylation is minimal. Thr-220 of GHF-1 is the homolog of the mitotic
      phosphoacceptor site responsible for the M-phase-specific inhibition of Oct-1 DNA
      binding Ser-382. As this site is conserved in all POU proteins, it appears that
      all members of this group are similarly regulated. A specific kinase activity
      distinct in its substrate specificity and susceptibility to inhibitors from the
      Cdc2 mitotic kinase or PKA was identified in extracts of mitotic cells. This
      novel activity could be involved in regulating the DNA binding activity of all
      POU proteins in a cell cycle-dependent manner.

PMID- 8524233
TI  - Regulation of Raf-1-dependent signaling during early Xenopus development.
AB  - The Raf-1 gene product is activated in response to cellular stimulation by a
      variety of growth factors and hormones. Raf-1 activity has been implicated in
      both cellular differentiation and proliferation. We have examined the regulation
      of the Raf-1/MEK/MAP kinase (MAPK) pathway during embryonic development in the
      frog Xenopus laevis. We report that Raf-1, MEK, and MAPK activities are turned
      off following fertilization and remain undetectable up until blastula stages
      (stage 8), some 4 h later. Tight regulation of the Raf-1/MEK/MAPK pathway
      following fertilization is crucial for embryonic cell cycle progression.
      Inappropriate reactivation of MAPK activity by microinjection of oncogenic Raf-1
      RNA results in metaphase cell cycle arrest and, consequently, embryonic
      lethality. Our findings demonstrate an absolute requirement, in vivo, for
      inactivation of the MAPK signaling pathway to allow normal cell cycle progression
      during the period of synchronous cell divisions which occur following
      fertilization. Further, we show that cytostatic factor effects are mediated
      through MEK and MAPK.

PMID- 8524235
TI  - Variant Max protein, derived by alternative splicing, associates with c-Myc in
      vivo and inhibits transactivation.
AB  - Max (Myc-associated factor X) is a basic helix-loop-helix/leucine zipper protein
      that has been shown to play a central role in the functional activity of c-Myc as
      a transcriptional activator. Max potentiates the binding of Myc-Max heterodimers
      through its basic region to its specific E-box Myc site (EMS), enabling c-Myc to
      transactivate effectively. In addition to the alternatively spliced exon a,
      several naturally occurring forms of alternatively spliced max mRNAs have been
      reported, but variant protein products from these transcripts have not been
      detected. Using Western blot (immunoblot) and immunoprecipitation analysis, we
      have identified a variant form of Max protein (16 to 17 kDa), termed dMax, in
      detergent nuclear extracts of murine B-lymphoma cells, normal B lymphocytes, and
      NIH 3T3 fibroblasts. Cloning and sequencing revealed that dMax contains a
      deletion spanning the basic region and helix 1 and the loop of the helix-loop
      helix region, presumably as a result of alternative splicing of max RNA. S1
      nuclease analysis confirmed the presence of the mRNA for dMax in cells. The dMax
      protein, prepared via in vitro transcription and translation, associated with
      bacterially synthesized Myc-glutathione S-transferase. Coimmunoprecipitation of
      dMax and c-Myc indicated their intracellular association. In vitro-synthesized
      dMax failed to bind EMS DNA, presumably because of the absence of the basic
      region. Coexpression of dMax inhibited EMS-mediated transactivation by c-Myc.
      Thus dMax, which can interact with c-Myc, appears to function as a dominant
      negative regulator, providing an additional level of regulation to the
      transactivation potential of c-Myc.

PMID- 8524236
TI  - Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression
      by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells.
AB  - 17 beta-Estradiol (E2) induces cathepsin D mRNA levels and intracellular levels
      of immunoreactive protein in MCF-7 human breast cancer cells. 2,3,7,8
      Tetrachlorodibenzo-p-dioxin (TCDD) alone does not affect cathepsin D gene
      expression in this cell line; however, in cells cotreated with TCDD and E2, TCDD
      inhibited E2-induced cathepsin D mRNA levels, the rate of gene transcription, and
      levels of immunoreactive protein. The inhibitory responses were observed within
      30 to 120 min after the cells were treated with TCDD. TCDD also inhibited E2
      induced secreted alkaline phosphatase activity in aryl hydrocarbon (Ah)
      responsive MCF-7 and wild-type mouse Hepa 1c1c7 cells cotransfected with the
      human estrogen receptor (hER) and the pBC12/S1/pac plasmid, which contains the 5'
      promoter region (-296/+57) of the cathepsin D gene and an alkaline phosphatase
      reporter gene. The E2-responsive ER/Sp1 sequence (-199 to -165) in the cathepsin
      D 5' region contains an imperfect GTGCGTG (-175/-181) xenobiotic responsive
      element (XRE); the role of this sequence in Ah responsiveness was investigated in
      gel electrophoretic mobility shift assays and with plasmid constructs containing
      a wild-type ER/Sp1 oligonucleotide or a mutant ER/Sp1-"XRE" oligonucleotide
      containing two C-->A mutations in the XRE sequence (antisense strand). In plasmid
      constructs which contained a chloramphenicol acetyltransferase reporter gene and
      the wild-type ER/Sp1 promoter sequence, E2-induced chloramphenicol
      acetyltransferase activity and mRNA levels were inhibited by TCDD whereas no
      inhibition was observed with the mutant ER/Sp1-"XRE" plasmids. Electrophoretic
      mobility shift assays showed that the nuclear or transformed cytosolic Ah
      receptor complex blocked formation of the ER-Sp1 complex with the wild-type but
      not the ER/Sp1 mutant oligonucleotide. Moreover, incubation of the wild-type
      bromodeoxyuridine-substituted ER/Sp1 oligonucleotide with the nuclear Ah receptor
      complex gave a specifically bound cross-linked 200-kDa band. These data
      demonstrate that Ah receptor-mediated inhibition of E2-induced cathepsin D gene
      expression is due to disruption of the ER-Sp1 complex by targeted interaction
      with an overlapping XRE.

PMID- 8524237
TI  - The hepatitis B virus X protein increases the cellular level of TATA-binding
      protein, which mediates transactivation of RNA polymerase III genes.
AB  - The hepatitis B virus X gene product transactivates a variety of cellular and
      viral genes. The mechanism for X induction of RNA polymerase (pol) III genes was
      investigated. By using Drosophila S-2 cells stably transformed with the X gene,
      the transient expression of a tRNA gene is enhanced. Comparing the
      transcriptional activities of extracts derived from these cells, all three types
      of RNA pol III promoters are stimulated by X. Interestingly, both S-2 and rat 1A
      cells stably transformed with the X gene produce increased cellular levels of the
      TATA-binding protein (TBP). By using various kinase inhibitors, it was found that
      the X-mediated increases in both transcription and TBP are dependent upon protein
      kinase C activation. Since TBP is a subunit of TFIIIB, the activity of this
      component fractionated from extracts derived from control and X-transformed cells
      was analyzed. These studies reveal that TFIIIB activity is substantially more
      limiting in control cells and that TFIIIB isolated from X-transformed cells has
      increased activity in reconstitution assays compared with TFIIIB isolated from
      control cells. Conversely, comparison of TFIIIC from control and X-transformed
      cell extracts revealed that there is relatively little change in its ability
      either to reconstitute transcription or to bind to DNA and that there is no
      change in the catalytic activity of RNA pol III. Studies were performed to
      determine whether directly increasing cellular TBP alone could enhance RNA pol
      III gene transcription. Transient expression of a TBP cDNA in rat 1A cells was
      capable of stimulating transcription activity from the resultant extracts in
      vitro. Together, these results demonstrate that one mechanism by which X mediates
      transactivation of RNA poll III genes is by increasing limiting TBP via the
      activation of cellular signaling pathways. The discovery that X increases
      cellular TBP, the universal transcription factor, provides a novel mechanism for
      the function of a viral transactivator protein and may explain the ability of X
      to produce such large and diverse effects on cellular gene expression.

PMID- 8524238
TI  - RNA polymerase bypass at sites of dihydrouracil: implications for transcriptional
      mutagenesis.
AB  - Dihydrouracil (DHU) is a major base damage product formed from cytosine following
      exposure of DNA to ionizing radiation under anoxic conditions. To gain insight
      into the DNA lesion structural requirements for RNA polymerase arrest or bypass
      at various DNA damages located on the transcribed strand during elongation, DHU
      was placed onto promoter-containing DNA templates 20 nucleotides downstream from
      the transcription start site. In vitro, single-round transcription experiments
      carried out with SP6 and T7 RNA polymerases revealed that following a brief pause
      at the DHU site, both enzymes efficiently bypass this lesion with subsequent
      rapid generation of full-length runoff transcripts. Direct sequence analysis of
      these transcripts indicated that both RNA polymerases insert primarily adenine
      opposite to the DHU site, resulting in a G-to-A transition mutation in the lesion
      bypass product. Such bypass and insertion events at DHU sites (or other types of
      DNA damages), if they occur in vivo, have a number of important implications for
      both the repair of such lesions and the DNA damage-induced production of mutant
      proteins at the level of transcription (transcriptional mutagenesis).

PMID- 8524239
TI  - Seven-up inhibits ultraspiracle-based signaling pathways in vitro and in vivo.
AB  - Seven-up (Svp), the Drosophila homolog of the chicken ovalbumin upstream
      transcription factor (COUP-TF); Ultraspiracle (Usp), the Drosophila homolog of
      the retinoid X receptor; and the ecdysone receptor are all members of the
      nuclear/steroid receptor superfamily. COUP-TF negatively regulates hormonal
      signaling involving retinoid X receptor in tissue culture systems. Here we
      demonstrate that Svp, like COUP-TF, can modulate Ultraspiracle-based hormonal
      signaling both in vitro and in vivo. Transfection assays in CV-1 cells
      demonstrate that Seven-up can inhibit ecdysone-dependent transactivation by the
      ecdysone receptor complex, a heterodimeric complex of Usp and ecdysone receptor.
      This repression depends on the dose of Svp and occurs with two different
      Drosophila ecdysone response elements. Ectopic expression of Svp in vivo induces
      lethality during early metamorphosis, the time of maximal ecdysone
      responsiveness. Concomitant overexpression of Usp rescues the larvae from the
      lethal effects of Svp. DNA binding studies show that Svp can bind to various
      direct repeats of the sequence AGGTCA but cannot bind to one of the ecdysone
      response elements used in the transient transfection assays. Our results suggest
      that Svp-mediated repression can occur by both DNA binding competition and
      protein-protein interactions.

PMID- 8524240
TI  - Identification of Rap1 as a target for the Crk SH3 domain-binding guanine
      nucleotide-releasing factor C3G.
AB  - C3G, which was identified as a Crk SH3 domain-binding guanine nucleotide
      releasing factor, shows sequence similarity to CDC25 and Sos family proteins (S.
      Tanaka, T. Morishita, Y. Hashimoto, S. Hattori, S. Nakamura, M. Shibuya, K.
      Matuoka, T. Takenawa, T. Kurata, K. Nagashima, and M. Matsuda, Proc. Natl. Acad.
      Sci. USA 91:3443-3447, 1994). The substrate specificity of C3G was examined by in
      vitro and in vivo experiments. C3G markedly stimulated dissociation of bound GDP
      from Rap1B but marginally affected the same reaction of other Ras family proteins
      (Ha-Ras, N-Ras, and RalA). C3G also stimulated binding of GTP-gamma S [guanosine
      5'-3-O-(thio)triphosphate] to Rap1B. When C3G and Rap1A were expressed in COS7
      cells, marked accumulation of the active GTP-bound form of Rap1A was observed,
      while Sos was not effective in the activation of Rap1A. These results clearly
      show that C3G is an activator for Rap1. Furthermore, expression of C3G with a
      membrane localization signal in a v-Ki-ras transformant, DT, induced a reversion
      of the cells to the flat form, possibly through the activation of endogenous
      Rap1.

PMID- 8524242
TI  - iPABP, an inducible poly(A)-binding protein detected in activated human T cells.
AB  - The poly(A)-binding protein (PABP) binds to the poly(A) tail present at the 3'
      ends of most eukaryotic mRNAs. PABP is thought to play a role in both translation
      and mRNA stability. Here we describe the molecular cloning and characterization
      of an inducible PABP, iPABP, from a cDNA library prepared from activated T cells.
      iPABP shows 79% sequence identity to PABP at the amino acid level. The RNA
      binding domains of iPABP and PABP are nearly identical, while their C termini are
      more divergent. Like PABP, iPABP is primarily localized to the cytoplasm. iPABP
      is expressed at low levels in resting normal human T cells; following T-cell
      activation, however, iPABP mRNA levels are rapidly up-regulated. In contrast,
      PABP is constitutively expressed in both resting and activated T cells. iPABP
      mRNA was also expressed at much higher levels than PABP mRNA in heart and
      skeletal muscle tissue. These data suggest that the regulation of cytoplasmic
      poly(A)-binding activity is more complex than previously believed. In most
      tissues, poly(A)-binding activity is likely to be the result of the combined
      effects of constitutively expressed PABP and iPABP, whose expression is subject
      to more complex regulation.

PMID- 8524241
TI  - A bipartite operator interacts with a heat shock element to mediate early meiotic
      induction of Saccharomyces cerevisiae HSP82.
AB  - Although key genetic regulators of early meiotic transcription in Saccharomyces
      cerevisiae have been well characterized, the activation of meiotic genes is still
      poorly understood in terms of cis-acting DNA elements and their associated
      factors. I report here that induction of HSP82 is regulated by the early meiotic
      IME1-IME2 transcriptional cascade. Vegetative repression and meiotic induction
      depend on interactions of the promoter-proximal heat shock element (HSE) with a
      nearby bipartite repression element, composed of the ubiquitous early meiotic
      motif, URS1 (upstream repression sequence 1), and a novel ancillary repression
      element. The ancillary repression element is required for efficient vegetative
      repression, is spatially separable from URS1, and continues to facilitate
      repression during sporulation. In contrast, URS1 also functions as a vegetative
      repression element but is converted early in meiosis into an HSE-dependent
      activation element. An early step in this transformation may be the antagonism of
      URS1-mediated repression by IME1. The HSE also nonspecifically supports a second
      major mode of meiotic activation that does not require URS1 but does require
      expression of IME2 and concurrent starvation. Interestingly, increased rather
      than decreased URS1-mediated vegetative transcription can be artificially
      achieved by introducing rare point mutations into URS1 or by deleting the UME6
      gene. These lesions offer insight into mechanisms of URS-dependent repression and
      activation. Experiments suggest that URS1-bound factors functionally modulate
      heat shock factor during vegetative transcription and early meiotic induction but
      not during heat shock. The loss of repression and activation observed when the
      IME2 activation element, T4C, is substituted for the HSE suggests specific
      requirements for URS1-upstream activation sequence interactions.

PMID- 8524243
TI  - Epidermal growth factor and Ras regulate gene expression in GH4 pituitary cells
      by separate, antagonistic signal transduction pathways.
AB  - We have previously demonstrated that epidermal growth factor (EGF) produces
      activation of the rat prolactin (rPRL) promoter in GH4 neuroendocrine cells via a
      Ras-independent mechanism. This Ras independence of the EGF response appears to
      be cell rather than promoter specific. Oncogenic Ras also produces activation of
      the rPRL promoter when transfected into GH4 cells and requires the sequential
      activation of Raf kinase, mitogen-activated protein (MAP) kinase, and c-Ets-1/GHF
      1 to mediate this response. In these studies, we have investigated the
      interaction between EGF and Ras in stimulating rPRL promoter activity and the
      role of Raf and MAP kinases in mediating the EGF response. We have also examined
      the role of several transcription factors and used various promoter mutants of
      the rPRL gene in order to better define the trans- and cis-acting components of
      the EGF response. EGF treatment of GH4 cells inhibits activation of the rPRL
      promoter produced by transfection of V12Ras from 24- to 4-fold in an EGF dose
      dependent manner. This antagonistic effect of EGF and Ras is mutual in that
      transfection of V12Ras also blocks EGF-induced activation of the rPRL promoter in
      a Ras dose-dependent manner, from 5.5- to 1.6-fold. Transfection of a plasmid
      encoding the dominant-negative Raf C4 blocks Ras-induced activation by 66% but
      fails to inhibit EGF-mediated activation of the rPRL promoter. Similarly,
      transfection of a construct encoding an inhibitory form of MAP kinase decreases
      the Ras response by 50% but does not inhibit the EGF response. Previous studies
      have demonstrated that c-Ets-1 is necessary and that GHF-1 acts synergistically
      with c-Ets-1 in the Ras response of the rPRL promoter. In contrast,
      overexpression of neither c-Ets-1 nor GHF-1 enhanced EGF-mediated activation of
      the rPRL promoter, and dominant-negative forms of these transcription factors
      failed to inhibit the EGF response. Using 5' deletion and site-specific
      mutations, we have mapped the EGF response to two regions on the proximal rPRL
      promoter. One region maps between -255 and -212, near the Ras response element,
      and a second maps between -125 and -54. The latter region appears to involve
      footprint 2, a previously identified repressor site on the rPRL promoter. Neither
      footprint 1 nor 3, known GHF-1 binding sites, appears to be crucial to RGF
      mediated rPRL promoter activation. The results of these studies indicate that in
      GH4 neuroendocrine cells, rPRL gene regulation by EGF is mediated by a signal
      transduction pathway that is separate and antagonistic to the Ras pathway. Hence,
      the functional role of the Ras/Raf/MAP kinase pathway in mediating
      transcriptional responses to EGF and other receptor tyrosine kinase may differ in
      highly specialized cell types.

PMID- 8524244
TI  - Wild-type human p53 transactivates the human proliferating cell nuclear antigen
      promoter.
AB  - The wild-type p53 protein is a transcriptional activator implicated in the
      control of cellular growth-related gene expression. Here, using a number of
      different cell lines and transient-transfection-transcription assays, we
      demonstrate that at low levels, wild-type p53 transactivates the human
      proliferating cell nuclear antigen (PCNA) promoter. When expressed at a similar
      level, the tumor-derived p53 mutants did not transactivate the PCNA promoter. We
      identified a p53-binding site on the human PCNA promoter with which p53 interacts
      sequence specifically. When placed on a heterologous synthetic promoter, the
      binding site functions as a wild-type p53 response element in either orientation.
      Deletion of the p53-binding site renders the PCNA promoter p53 nonresponsive,
      showing that wild-type p53 transactivates the PCNA promoter by binding to the
      site. At a higher concentration, wild-type p53 inhibits the PCNA promoter but p53
      mutants activate. Transactivation by p53 mutants does not require the p53-binding
      site. These observations suggest that moderate elevation of the cellular wild
      type p53 level induces PCNA production to help in DNA repair.

PMID- 8524245
TI  - Kinetoplast maxicircle DNA replication in Crithidia fasciculata and Trypanosoma
      brucei.
AB  - Kinetoplast DNA, the mitochondrial DNA of trypanosomatids, is composed of several
      thousand minicircles and a few dozen maxicircles, all of which are topologically
      interlocked in a giant network. We have studied the replication of maxicircle
      DNA, using electron microscopy to analyze replication intermediates from both
      Crithidia fasciculata and Trypanosoma brucei. Replication intermediates were
      stabilized against branch migration by introducing DNA interstrand cross-links in
      vivo with 4,5',8-trimethylpsoralen and UV radiation. Electron microscopy of
      individual maxicircles resulting from a topoisomerase II decatenation of
      kinetoplast DNA networks revealed intact maxicircle theta structures. Analysis of
      maxicircle DNA linearized by restriction enzyme cleavage revealed branched
      replication intermediates derived from theta structures. Measurements of the
      linearized branched molecules in both parasites indicate that replication
      initiates in the variable region (a noncoding segment characterized by repetitive
      sequences) and proceeds unidirectionally, clockwise on the standard map.

PMID- 8524246
TI  - Progesterone receptor structure and function altered by geldanamycin, an hsp90
      binding agent.
AB  - The assembly of progesterone receptor (PR) heterocomplexes in vitro involves at
      least eight components of the molecular chaperone machinery, and as earlier
      reports have shown, these proteins exhibit complex, dynamic, but ordered,
      interactions with one another and PR. Using the selective hsp90 binding agent
      geldanamycin (GA), we have found that PR assembly in vitro can be arrested at a
      previously observed intermediate assembly step. Like mature PR complexes, the
      intermediate complexes contain hsp90, but they differ from mature complexes by
      the presence of hsp70, p60, and p48 and the absence of immunophilins and p23.
      Arrest of PR assembly is likely due to GA's ability to directly block binding of
      p23 to hsp90. An important functional consequence of GA-mediated assembly arrest
      in vitro is the inability of the resulting PR complexes to bind progesterone,
      despite the presence of hsp90 in the receptor complexes. The biological
      significance of the in vitro observations is demonstrated by GA's ability to (i)
      rapidly block PR's hormone binding capacity in intact cells and (ii) alter the
      composition of COS cell PR complexes in a manner similar to that observed during
      in vitro reconstitutions. An updated model for the cyclic assembly pathway of PR
      complexes that incorporates the present findings with earlier results is
      presented.

PMID- 8524247
TI  - Tyrosine dephosphorylation of nuclear proteins mimics transforming growth factor
      beta 1 stimulation of alpha 2(I) collagen gene expression.
AB  - Transforming growth factor beta 1 (TGF-beta 1) exerts a positive effect on the
      transcription of genes coding for several extracellular matrix-related products,
      including collagen I. We have previously identified a strong TGF-beta 1
      responsive element (TbRE) in the upstream promoter sequence of the alpha 2(I)
      collagen (COL1A2) gene. Our experiments have shown that TGF-beta 1 stimulates
      COL1A2 transcription by increasing binding of an Sp1-containing complex (TbRC) to
      the TbRE. They have also suggested that the change occurs via posttranslational
      modification of a protein(s) directly or indirectly interacting with Sp1. Here,
      we provide evidence showing that tyrosine dephosphorylation of nuclear proteins
      mimics the stimulation of COL1A2 transcription by the TGF-beta 1-activated
      signaling pathway. Preincubation of nuclear extracts with protein tyrosine
      phosphatase (PTPase) but not with protein phosphatase type 2A (PP2A), a
      serine/threonine phosphatase, enhanced binding of the TbRC to the same degree as
      culturing cells in TGF-beta 1. Consistent with these in vitro findings,
      genistein, a tyrosine kinase inhibitor, led to markedly increased COL1A2 gene
      expression, whereas sodium orthovanadate, a tyrosine phosphatase inhibitor,
      decreased it substantially. These results were supported by transfection
      experiments showing that genistein and sodium orthovanadate have opposite effects
      on TbRE-mediated transcription. Moreover, nuclear proteins isolated from
      genistein-treated cells were found to interact with the TbRE significantly more
      than those from untreated cells. Furthermore, pretreatment of cells with sodium
      orthovanadate virtually abrogated nuclear protein binding to the TbRE, but not to
      a neighboring cis-acting element unresponsive to TGF-beta 1. The results of this
      study, therefore, provide the first correlation between tyrosine
      dephosphorylation, increased binding of a transcriptional complex, and TGF-beta 1
      stimulation of gene expression.

PMID- 8524248
TI  - CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase
      association and activation.
AB  - T-cell activation involves two distinct signal transduction pathways. Antigen
      specific signaling events are initiated by T-cell receptor recognition of cognate
      peptide presented by major histocompatibility complex molecules. Costimulatory
      signals, which are required for optimal T-cell activation and for overcoming the
      induction of anergy, can be provided by the homodimeric T-cell glycoprotein CD28
      through its interaction with the counterreceptors B7-1 and B7-2 on antigen
      presenting cells. Ligation of CD28 results in its phosphorylation on tyrosines
      and the subsequent recruitment and activation of phosphatidylinositol 3-kinase
      (PI 3-kinase). It has been suggested that the induced association of CD28 and PI
      3-kinase is required for costimulation. We report here that ligation of CD19, a
      heterologous B-cell receptor that also associates with and activates PI 3-kinase
      upon ligation, failed to costimulate interleukin-2 production. Moreover,
      pharmacological inhibition of PI 3-kinase activity failed to block costimulation
      mediated by CD28. By mutational analysis, we demonstrate that disruption of PI 3
      kinase association with CD28 also did not abrogate costimulation. These results
      argue that PI 3-kinase association with CD28 is neither necessary nor sufficient
      for costimulation of interleukin-2 production. Finally, we identify specific
      amino acid residues required for CD28-mediated costimulatory activity.

PMID- 8524249
TI  - Differential inhibition of signaling pathways by dominant-negative SH2/SH3
      adapter proteins.
AB  - SH2/SH3 adapters are thought to function in signal transduction pathways by
      coupling inputs from tyrosine kinases to downstream effectors such as Ras.
      Members of the mitogen-activated protein kinase family are known to be activated
      by a variety of mitogenic stimuli, including tyrosine kinases such as Abl and the
      epidermal growth factor (EGF) receptor. We have used activation of the mitogen
      activated protein kinase Erk-1 as a model system with which to examine whether
      various dominant-negative SH2/SH3 adapters (Grb2, Crk, and Nck) could block
      signaling pathways leading to Erk activation. Activation of Erk-1 by oncogenic
      Abl was effectively inhibited by Grb2 with mutations in either its SH2 or SH3
      domain or by Crk-1 with an SH3 domain mutation. The Crk-1 SH2 mutant was less
      effective, while Nck SH2 and SH3 mutants had little or no effect on Erk
      activation. These results suggest that both Crk and Grb2 may contribute to the
      activation of Erk by oncogenic Abl, whereas Nck is unlikely to participate in
      this pathway. Next we examined whether combinations of these dominant-negative
      adapters could inhibit Erk activation more effectively than each mutant alone.
      When combinations of Crk-1 and Grb2 mutants were analyzed, the combination of the
      Crk-1 SH3 mutant plus the Grb2 SH3 mutant gave a striking synergistic effect.
      This finding suggests that in Abl-transformed cells, more than one class of
      tyrosine-phosphorylated sites (those that bind the Grb2 SH2 domain and those that
      bind the Crk SH2 domain) can lead to Ras activation. In contrast to results with
      Abl, Erk activation by EGF was strongly inhibited only by Grb2 mutants; Crk and
      Nck mutants had little or no effect. This finding suggests that Grb2 is the only
      adapter involved in the activation of Erk by EGF. Dominant-negative adaptors
      provide a novel means to identify binding interactions important in vivo for
      signaling in response to a variety of stimuli.

PMID- 8524250
TI  - Checkpoint genes required to delay cell division in response to nocodazole
      respond to impaired kinetochore function in the yeast Saccharomyces cerevisiae.
AB  - Inhibition of mitosis by antimitotic drugs is thought to occur by destruction of
      microtubules, causing cells to arrest through the action of one or more mitotic
      checkpoints. We have patterned experiments in the yeast Saccharomyces cerevisiae
      after recent studies in mammalian cells that demonstrate the effectiveness of
      antimitotic drugs at concentrations that maintain spindle structure. We show that
      low concentrations of nocodazole delay cell division under the control of the
      previously identified mitotic checkpoint genes BUB1, BUB3, MAD1, and MAD2 and
      independently of BUB2. The same genes mediate the cell cycle delay induced in
      ctf13 mutants, limited for an essential kinetochore component. Our data suggest
      that a low concentration of nocodazole induces a cell cycle delay through
      checkpoint control that is sensitive to impaired kinetochore function. The BUB2
      gene may be part of a separate checkpoint that responds to abnormal spindle
      structure.

PMID- 8524251
TI  - Increased expression of LD1 genes transcribed by RNA polymerase I in Leishmania
      donovani as a result of duplication into the rRNA gene locus.
AB  - Eukaryotic protein-coding genes are generally transcribed by RNA polymerase II
      (Pol II), which has a lower transcription rate than that of Pol I. We report here
      the duplication of two LD1 genes into the rRNA locus and their resultant
      transcription by Pol I. The multigenic LD1 locus is present in a 2.2-Mb
      chromosome in all stocks of Leishmania spp. and is also present in multicopy 200-
      to 450-kb linear chromosomes or multicopy circular DNAs in over 15% of stocks
      examined. Genomic rearrangement in Leishmania donovani LSB-51.1 resulted in
      duplication of a 3.9-kb segment of LD1 containing two genes (orfF and orfG) and
      of a 1.3-kb segment from approximately 10 kb downstream into the rRNA gene repeat
      region of the 1.2-Mb chromosome. Short sequences (12 or 13 bp) common to the 2.2
      Mb LD1 and 1.2-Mb rRNA loci suggest that this gene conversion occurred by
      homologous recombination. Transcription of the duplicated genes is alpha-amanitin
      resistant, indicating transcription by Pol I, in contrast to the alpha-amanitin
      sensitive (Pol II) transcription of the genes in the 2.2-Mb LD1 locus. This
      results in higher transcript abundance than expected from the gene copy number in
      LSB-51.1 and in elevated expression of at least the orfF gene product.

PMID- 8524252
TI  - SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and
      pseudohyphal development by repressing transcription.
AB  - Yeast cyclic AMP (cAMP)-dependent protein kinase (PKA) activity is essential for
      growth and cell cycle progression. Dependence on PKA function can be partially
      relieved by overexpression of a gene, SOK2, whose product has significant
      homology with several fungal transcription factors (StuA from Aspergillus
      nidulans and Phd1 from Saccharomyces cerevisiae) that are associated with
      cellular differentiation and development. Deletion of SOK2 is not lethal but
      exacerbates the growth defect of strains compromised for PKA activity.
      Alterations in Sok2 protein production also affect the expression of genes
      involved in several other PKA-regulated processes, including glycogen
      accumulation (GAC1) and heat shock resistance (SSA3). These results suggest SOK2
      plays a general regulatory role in the PKA signal transduction pathway.
      Expression of the PKA catalytic subunit genes is unaltered by deletion or
      overexpression of SOK2. Because homozygous sok2/sok2 diploid strains form
      pseudohyphae at an accelerated rate, the Sok2 protein may inhibit the switch from
      unicellular to filamentous growth, a process that is dependent on cAMP. Thus, the
      product of SOK2 may act downstream of PKA to regulate the expression of genes
      important in growth and development.

PMID- 8524253
TI  - E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis.
AB  - The E2F DNA binding activity consists of a heterodimer between E2F and DP family
      proteins, and these interactions are required for association of E2F proteins
      with pRb and the pRb-related proteins p107 and p130, which modulate E2F
      transcriptional activities. E2F-1 expression is sufficient to release fibroblasts
      from G0 and induce entry into S phase, yet it also initiates apoptosis. To
      investigate the mechanisms of E2F-induced apoptosis, we utilized interleukin-3
      (IL-3)-dependent 32D.3 myeloid cells, a model of hematopoietic progenitor
      programmed cell death. In the absence of IL-3, E2F-1 alone was sufficient to
      induce apoptosis, and p53 levels were diminished. DP-1 alone was not sufficient
      to induce cell cycle progression or alter rates of death following IL-3
      withdrawal. However, overexpression of both E2F-1 and DP-1 led to the rapid death
      of cells even in the presence of survival factors. In the presence of IL-3,
      levels of endogenous wild-type p53 increased in response to E2F-1, and
      coexpression of DP-1 further augmented p53 levels. These results provide evidence
      that E2F is a functional link between the tumor suppressors p53 and pRb. However,
      induction of p53 alone was not sufficient to trigger apoptosis, suggesting that
      the ability of E2F to override survival factors involves additional effectors.

PMID- 8524254
TI  - Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is
      required for oligomycin resistance in Saccharomyces cerevisiae.
AB  - Semidominant mutations in the PDR1 or PDR3 gene lead to elevated resistance to
      cycloheximide and oligomycin. PDR1 and PDR3 have been demonstrated to encode zinc
      cluster transcription factors. Cycloheximide resistance mediated by PDR1 and PDR3
      requires the presence of the PDR5 membrane transporter-encoding gene. However,
      PDR5 is not required for oligomycin resistance. Here, we isolated a gene that is
      necessary for PDR1- and PDR3-mediated oligomycin resistance. This locus,
      designated YOR1, causes a dramatic elevation in oligomycin resistance when
      present in multiple copies. A yor1 strain exhibits oligomycin hypersensitivity
      relative to an isogenic wild-type strain. In addition, loss of the YOR1 gene
      blocks the elevation in oligomycin resistance normally conferred by mutant forms
      of PDR1 or PDR3. The YOR1 gene product is predicted to be a member of the ATP
      binding cassette transporter family of membrane proteins. Computer alignment
      indicates that Yor1p shows striking sequence similarity with multidrug resistance
      associated protein, Saccharomyces cerevisiae Ycf1p, and the cystic fibrosis
      transmembrane conductance regulator. Use of a YOR1-lacZ fusion gene indicates
      that YOR1 expression is responsive to PDR1 and PDR3. While PDR5 expression is
      strictly dependent on the presence of PDR1 or PDR3, control of YOR1 expression
      has a significant PDR1/PDR3-independent component. Taken together, these data
      indicate that YOR1 provides the link between transcriptional regulation by PDR1
      and PDR3 and oligomycin resistance of yeast cells.

PMID- 8524255
TI  - Mutations altering the mitochondrial-cytoplasmic distribution of Mod5p implicate
      the actin cytoskeleton and mRNA 3' ends and/or protein synthesis in mitochondrial
      delivery.
AB  - The Saccharomyces cerevisiae MOD5 gene encodes proteins that function in three
      subcellular locations: mitochondria, the cytoplasm, and nuclei (M. Boguta, L.A.
      Hunter, W.-C. Shen, E. C. Gillman, N. C. Martin, and A. K. Hopper, Mol. Cell.
      Biol. 14:2298-2306, 1994; E. C. Gillman, L. B. Slusher, N. C. Martin, and A. K.
      Hopper, Mol. Cell. Biol. 11:2382-2390, 1991). A mutant allele of MOD5 encoding a
      protein (Mod5p-I,KR6) located predominantly in mitochondria was constructed.
      Mutants defective in delivering Mod5p-I,KR6 to mitochondria were sought by
      selecting cells with increased cytosolic activity of this protein. Twenty-five
      mutants defining four complementation groups, mdp1, mdp2, mdp3, and mdp4, were
      found. They are unable to respire at 34 degrees C or to grow on glucose medium at
      38 degrees C. Cell fractionation studies showed that mdp1, mdp2, and mdp3 mutants
      have an altered mitochondrial-cytoplasmic distribution of Mod5p. mdp2 can be
      suppressed by ACT1, the actin-encoding gene. The actin cytoskeleton organization
      is also aberrant in mdp2 cells. MDP2 is the same as VRP1 (S. F. H. Donnelly, M.
      J. Picklington, D. Pallotta, and E. Orr, Mol. Microbiol. 10:585-596, 1993). MDP3
      is identical to PAN1, which encodes a protein that interacts with mRNA 3' ends
      and affects initiation of protein synthesis (A. B. Sachs and J. A. Deardoff, Cell
      70:961-973, 1992). These results implicate the actin cytoskeleton and mRNA 3'
      ends and/or protein synthesis as being as important for protein distribution in
      S. cerevisiae as they are for distribution of cytosolic proteins in higher
      eukaryotes. This provides the potential to apply genetic and molecular approaches
      to study gene products and mechanisms involved in this type of protein
      distribution. The selection strategy also offers a new approach for identifying
      gene products involved in the distribution of proteins to their subscellular
      destinations.

PMID- 8524256
TI  - Six human RNA polymerase subunits functionally substitute for their yeast
      counterparts.
AB  - To assess functional relatedness of individual components of the eukaryotic
      transcription apparatus, three human subunits (hsRPB5, hsRPB8, and hsRPB10) were
      tested for their ability to support yeast cell growth in the absence of their
      essential yeast homologs. Two of the three subunits, hsRPB8 and hsRPB10,
      supported normal yeast cell growth at moderate temperatures. A fourth human
      subunit, hsRPB9, is a homolog of the nonessential yeast subunit RPB9. Yeast cells
      lacking RPB9 are unable to grow at high and low temperatures and are defective in
      mRNA start site selection. We tested the ability of hsRPB9 to correct the growth
      and start site selection defect seen in the absence of RPB9. Expression of hsRPB9
      on a high-copy-number plasmid, but not a low-copy-number plasmid, restored growth
      at high temperatures. Recombinant human hsRPB9 was also able to completely
      correct the start site selection defect seen at the CYC1 promoter in vitro as
      effectively as the yeast RPB9 subunit. Immunoprecipitation of the cell extracts
      from yeast cells containing either of the human subunits that function in place
      of their yeast counterparts in vivo suggested that they assemble with the
      complete set of yeast RNA polymerase II subunits. Overall, a total of six of the
      seven human subunits tested previously or in this study are able to substitute
      for their yeast counterparts in vivo, underscoring the remarkable similarities
      between the transcriptional machineries of lower and higher eukaryotes.

PMID- 8524257
TI  - In vivo structure of the human cdc2 promoter: release of a p130-E2F-4 complex
      from sequences immediately upstream of the transcription initiation site
      coincides with induction of cdc2 expression.
AB  - In quiescent cells, cdc2 mRNA is almost undetectable. Stimulation of cells to
      reenter the cell cycle results in induction of cdc2 expression, beginning at the
      G1-to-S transition and reaching maximum levels during late S and G2 phases. To
      investigate cdc2 transcriptional regulation throughout cell cycle progression, we
      monitored protein-DNA interactions by in vivo footprinting along 800 bp of the
      human cdc2 promoter in quiescent fibroblasts and at different time points
      following serum stimulation. We found 11 in vivo protein-binding sites, but no
      protein binding was observed at a high-affinity E2F site that had previously been
      implicated in cdc2 regulation. Nine of the identified in vivo binding sites
      (among them were two inverted CCAAT boxes, two Sp1 sites, and one ets-2 site)
      bind transcription factors constitutively throughout the cell cycle. However, at
      two elements located at positions -60 and -20 relative to the transcription start
      site, the binding pattern changes significantly as the cells are entering S
      phase. A G0- and G1-specific protein complex disappears at the -20 element at the
      beginning of S phase. This sequence deviates at one base position from known E2F
      consensus binding sites. We found that the major E2F activity in human
      fibroblasts contains E2F-4 and p130. The -20 element of the cdc2 gene
      specifically interacts with a subset of E2F-4-p130 complexes present in G0 cells
      but does not interact with S-phase-specific E2F complexes. Transient-transfection
      experiments with wild-type and mutant cdc2 promoter constructs indicate that the 
      20 element is involved in suppressing cdc2 activity in quiescent cells. We
      suggest that the presence of the p130-E2F-4 complex in G0/G1 blocks access of
      components of the basal transcription machinery or prevents transaction by the
      constitutively bound upstream activator proteins.

PMID- 8524258
TI  - Palmitoylation of either Cys-3 or Cys-5 is required for the biological activity
      of the Lck tyrosine protein kinase.
AB  - Palmitoylation can regulate both the affinity for membranes and the biological
      activity of proteins. To study the importance of the palmitoylation of the Src
      like tyrosine protein kinase p56lck in the function of the protein, Cys-3, Cys-5,
      or both were mutated to serine, and the mutant proteins were expressed stably in
      fibroblasts and T cells. Both Cys-3 and Cys-5 were apparent sites of
      palmitoylation in Lck expressed in fibroblasts, as only the simultaneous mutation
      of both Cys-3 and Cys-5 caused a large reduction in the incorporation of
      [3H]palmitic acid. The double mutant S3/5Lck was no longer membrane bound when
      examined by either immunofluorescence or cell fractionation. This indicated that
      palmitoylation was required for association of Lck with the plasma membrane.
      Since the S3/5Lck protein was myristoylated, myristoylation of Lck is not
      sufficient for membrane binding. When Cys-3, Cys-5, or both Cys-3 and Cys-5 were
      changed to serine in activated F505Lck, palmitoylation of either Cys-3 or Cys-5
      was found to be necessary and sufficient for the transformation of fibroblasts
      and for the induction of spontaneous, antigen-independent interleukin-2
      production in the T-helper cell line DO-11.10. Nonpalmitoylated F505Lck exhibited
      little activity in vivo, where it did not induce elevated levels of tyrosine
      phosphorylation, and in vitro, where it was unable to phosphorylate angiotensin
      in an in vitro kinase assay. These findings suggest that F505Lck must be anchored
      stably to membranes to become activated. Because palmitoylation is dynamic, it
      may be involved in regulating the cellular localization of p56(lck), and
      consequently its activity, by altering the proximity of p56(lck) to its
      activators and/or targets.

PMID- 8524259
TI  - Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH)
      proteins maps outside the bHLH domain and suggests two separable modes of
      transcriptional repression.
AB  - The Hairy/Enhancer of split/Deadpan family of basic helix-loop-helix (bHLH)
      proteins function as transcriptional repressors. We have examined the mechanisms
      of repression used by the Hairy and E(SPL) proteins by assaying the antagonism
      between wild-type or altered Hairy/E(SPL) and Scute bHLH proteins during sex
      determination in Drosophila melanogaster. Domain swapping and mutagenesis of the
      Hairy and E(SPL) proteins show that three evolutionarily conserved domains are
      required for their function: the bHLH, Orange, and WRPW domains. However, the
      suppression of Scute activity by Hairy does not require the WRPW domain. We show
      that the Orange domain is an important functional domain that confers specificity
      among members of the Hairy/E(SPL) family. In addition, we show that a Xenopus
      Hairy homology conserves not only Hairy's structure but also its biological
      activity in our assays. We propose that transcriptional repression by the
      Hairy/E(SPL) family of bHLH proteins involves two separable mechanisms:
      repression of specific transcriptional activators, such as Scute, through the
      bHLH and Orange domains and repression of other activators via interaction of the
      C-terminal WRPW motif with corepressors, such as the Groucho protein.

PMID- 8524260
TI  - Bovine latent transforming growth factor beta 1-binding protein 2: molecular
      cloning, identification of tissue isoforms, and immunolocalization to elastin
      associated microfibrils.
AB  - Monoclonal antibodies to fibrillin 1 (MP340), a component of elastin-associated
      microfibrils, were used to screen cDNA libraries made from bovine nuchal ligament
      mRNA. One of the selected clones (cL9; 1.2 kb) hybridized on Northern (RNA)
      blotting with nuchal ligament mRNA to two abundant mRNAs of 9.0 and 7.5 kb, which
      were clearly distinct from fibrillin mRNA (10 kb). Further library screening and
      later reverse transcription PCR by the rapid amplification of cDNA ends (RACE)
      technique resulted in the isolation of additional overlapping cDNAs corresponding
      to about 6.7 kb of the mRNA. The encoded protein exhibited sequence similarity of
      around 80% with a recently identified human protein named latent transforming
      growth factor beta 1 (TGF-beta 1)-binding protein 2 (LTBP-2), indicating that the
      new protein was bovine LTBP-2. This was confirmed by the specific localization of
      bovine LTBP-2 cDNA probes to human chromosome 14q24.3, which is the locus of the
      human LTBP-2 gene. The domain structure of bovine LTBP-2 is very similar to that
      of the human LTBP-2, containing 20 examples of 6-cysteine epidermal growth factor
      like repeats, 16 of which have the consensus sequence for calcium binding,
      together with 4 examples of 8-cysteine motifs characteristic of fibrillins and
      LTBP-1. A 4-cysteine sequence which is unique to bovine LTBP-2 and which has
      similarity to the 8-cysteine motifs was also present. Antibodies raised to two
      unique bovine LTBP-2 peptides specifically localized in tissue sections to the
      elastin-associated microfibrils, indicating that LTBP-2 is closely associated
      with these structures. Immunoblotting experiments identified putative LTBP-2
      isoforms as a 260-kDa species released into the medium by cultured elastic tissue
      cells and as larger 290- and 310-kDa species in tissue extracts. A major
      proportion of tissue-derived LTBP-2 required treatment with 6 M guanidine for
      solubilization, indicating that the protein was strongly bound to the
      microfibrils. Most of the guanidine-solubilized LTBP-2 appeared to be monomeric,
      indicating that it was not involved in disulfide-bonded aggregation either with
      itself or with latent TGF-beta. Additional LTBP-2 was resistant to solubilization
      with 6 M guanidine but was readily extracted with a reductive saline solution.
      This treatment is relatively specific for solubilization of microfibrillar
      constituents including fibrillin 1 and microfibril-associated glycoprotein.
      Therefore, it can be inferred that some LTBP-2 is bound covalently to the
      microfibrils by reducible disulfide linkages. The evidence suggests that LTBP-2
      has a direct role in elastic fiber structure and assembly which may be
      independent of its growth factor-binding properties. Thus, LTBP-2 appears to
      share functional characteristics with both LTBP-1 and fibrillins.

PMID- 8524261
TI  - Regulation of Drosophila yolk protein genes by an ovary-specific GATA factor.
AB  - The divergently transcribed yolk protein genes (Yp1 and Yp2) of Drosophila
      melanogaster are expressed only in adult females, in fat body tissue and in
      ovarian follicle cells. Using an in vitro transcription assay, we have identified
      a single 12-bp DNA element that activates transcription from the promoters of
      both Yp genes. In vivo, this regulatory element is tissue specific: it activates
      transcription of Yp1 and Yp2 reporter genes in follicle cells but has no
      detectable effect in fat body or other tissues. The sequence of the element
      consists of two recognition sites for the GATA family of transcription factors.
      We show that among the Drosophila genes known to encode GATA factors, only dGATAb
      is expressed in ovaries. The single transcript that we detect in ovaries is
      alternatively spliced or initiated to produce an ovary-specific isoform of the
      protein. Bacterially expressed dGATAb binds to the 12-bp element; a similar
      binding activity is also present in the Kc0 nuclear extracts used for in vitro
      transcription assays. These in vitro and in vivo results lead us to propose that
      dGATAb makes several developmentally regulated products, one of which is a
      follicle cell-specific protein activating transcription of Yp1 and Yp2 from a
      known regulatory element.

PMID- 8524262
TI  - Regulation of p53-mediated apoptosis and cell cycle arrest by Steel factor.
AB  - Activation of the p53 protein can lead to apoptosis and cell cycle arrest. In
      contrast, activation of the signalling pathway controlled by the Kit receptor
      tyrosine kinase prevents apoptosis and promotes cell division of a number of
      different cell types in vivo. We have investigated the consequences of activating
      the Kit signalling pathway by its ligand Steel factor on these opposing functions
      of the p53 protein in Friend erythroleukemia cells. A temperature-sensitive p53
      allele (Val-135) was introduced into the Friend erythroleukemia cell line (DP-16)
      which lacks endogenous p53 expression. At 38.5 degrees C, the Val-135 protein
      maintains a mutant conformation and has no effect on cell growth. At 32 degrees
      C, the mutant protein assumes wild-type properties and induces these cells to
      arrest in G1, terminally differentiate, and die by apoptosis. We demonstrate that
      Steel factor inhibits p53-mediated apoptosis and differentiation but has no
      effect on p53-mediated G1/S cell cycle arrest. These results demonstrate that
      Steel factor functions as a cell survival factor in part through the suppression
      of differentiation and apoptosis induced by p53 and suggest that cell cycle
      arrest and apoptosis may be separable functions of p53.

PMID- 8524263
TI  - An immunological renal disease in transgenic mice that overexpress Fli-1, a
      member of the ets family of transcription factor genes.
AB  - The proto-oncogene Fli-1 is a member of the ets family of transcription factor
      genes. Its high expression in the thymus and spleen and the presence of DNA
      binding sites for Fli-1 in a number of lymphoid cell-specific gene suggest that
      Fli-1 is involved in the regulation of lymphopoiesis. Activation of the Fli-1
      gene by either chromosomal translocation or viral insertion leads to Ewing's
      sarcoma in humans and erythroleukemia in mice, respectively. Thus, Fli-1 is
      normally involved in pathways involved in the regulation of cell growth and
      differentiation. We have generated H-2Kk-Fli-1 transgenic mice that overexpress
      Fli-1 in various mouse tissues, with the highest levels of Fli-1 protein in the
      thymus and spleen. These Fli-1 transgenic mice developed a high incidence of a
      progressive immunological renal disease and ultimately died of renal failure
      caused by tubulointerstitial nephritis and immune-complex glomerulonephritis. The
      incidences of renal disease correlated with the levels of Fli-1 protein in
      lymphoid tissues of transgenic lines. The hypergammaglobulinemia, splenomegaly, B
      cell hyperplasia, accumulation of abnormal CD3+ B220+ T lymphoid cells and CD5+
      B220+ B cells in peripheral lymphoid tissues, and detection of various
      autoantibodies in the sera of diseased Fli-1 transgenic mice suggested the
      involvement of an immune dysfunction in the pathogenesis of the renal disease. In
      addition, splenic B cells from transgenic mice exhibited increased proliferation
      and prolonged survival in vitro in response to mitogens. Taken together, these
      data suggest that overexpression or ectopic expression of Fli-1 perturbs normal
      lymphoid cell function and programmed cell death. Thus, H-2Kk-Fli-1 transgenic
      mice may serve as a murine model for autoimmune disease in humans, such as
      systemic lupus erythematosus.

PMID- 8524264
TI  - Cotranscriptional splicing of a group I intron is facilitated by the Cbp2
      protein.
AB  - The nuclear CBP2 gene encodes a protein essential for the splicing of a
      mitochondrial group I intron in Saccharomyces cerevisiae. This intron (bI5) is
      spliced autocatalytically in the presence of high concentrations of magnesium and
      monovalent salt but requires the Cbp2 protein for splicing under physiological
      conditions. Addition of Cbp2 during RNA synthesis permitted cotranscriptional
      splicing. Splicing did not occur in the transcription buffer in the absence of
      synthesis. The Cbp2 protein appeared to modify the folding of the intron during
      RNA synthesis: pause sites for RNA polymerase were altered in the presence of the
      protein, and some mutant transcripts that did not splice after transcription did
      so during transcription in the presence of Cbp2. Cotranscriptional splicing also
      reduced hydrolysis at the 3' splice junction. These results suggest that Cbp2
      modulates the sequential folding of the ribozyme during its synthesis. In
      addition, splicing during transcription led to an increase in RNA synthesis with
      both T7 RNA polymerase and mitochondrial RNA polymerase, implying a functional
      coupling between transcription and splicing.

PMID- 8524265
TI  - Effects of mutations in the Saccharomyces cerevisiae RNA14, RNA15, and PAP1 genes
      on polyadenylation in vivo.
AB  - The RNA14 and RNA15 gene products have been implicated in a variety of cellular
      processes. Mutations in these genes lead to faster decay of some mRNAs and yield
      extracts that are deficient in cleavage and polyadenylation in vitro. These
      results suggest that the RNA14 and RNA15 gene products may be involved in both
      adenylation and deadenylation in vivo. To explore the roles of these gene
      products in vivo, we examined the site of adenylation and the rate of
      deadenylation for individual mRNAs in rna14 and rna15 mutant strains. We observed
      that the rates of deadenylation are not affected by lesions in either the RNA14
      or the RNA15 gene. This result suggests that the proteins encoded by these genes
      are not involved in regulation of the deadenylation rate. In contrast, we
      observed that the site of adenylation for the ACT1 transcript can be altered in
      these mutants. Interestingly, we also observed that mutation of the poly(A)
      polymerase gene altered the site of ACT1 polyadenylation. These observations
      suggest that the RNA14, RNA15, and PAP1 proteins are involved in poly(A) site
      choice. This alteration in poly(A) site choice in the rna14 mutant can be
      corrected by the ssm4 suppressor, indicating that this suppression acts at the
      level of polyadenylation and not by slowing mRNA degradation.

PMID- 8524266
TI  - Constitutive repression and nuclear factor I-dependent hormone activation of the
      mouse mammary tumor virus promoter in Saccharomyces cerevisiae.
AB  - To study the influence of various transactivators and the role of nucleosomal
      structure in gene regulation by steroid hormones, we have introduced mouse
      mammary tumor virus (MMTV) promoter sequences along with expression vectors for
      the glucocorticoid receptor (GR) and nuclear factor I (NFI) in Saccharomyces
      cerevisiae, an organism amenable to genetic manipulation. Both in the context of
      an episomal multicopy vector and in a centromeric single-copy plasmid, the MMTV
      promoter was virtually silent in the absence of inducer, even in yeast strains
      expressing GR and NFI. Induction was optimal with deacylcortivazol and required
      both GR and NFI. The transactivation function AF1 in the N-terminal half of GR is
      required for ligand-dependent induction and acts constitutively in truncated GR
      lacking the ligand binding domain. A piece of the MMTV long terminal repeat
      extending from -236 to +111 is sufficient to position a nucleosome, B, over the
      regulatory region of the promoter from -45 to -190 and another nucleosome over
      the transcription start region. The rotational orientation of the DNA on the
      surface of nucleosome B is the same as that previously found in animal cells and
      in reconstitution experiments. This orientation is compatible with binding of GR
      to two sites, while it should preclude binding of NFI and hence be responsible
      for constitutive repression. Upon ligand induction, there is no major chromatin
      rearrangement, but the proximal linker DNA, including the TATA box, becomes
      hypersensitive to nucleases. The transcriptional behavior of the MMTV promoter
      was unaffected by deletions of the genes for zuotin or SIN1/SPT2, two proteins
      which have been claimed to assume some of the functions of linker histones. Thus,
      despite the lack of histone H1, yeast cells could be a suitable system to study
      the contribution of nucleosomal organization to the regulated expression of the
      MMTV promoter.

PMID- 8524267
TI  - Do products of the myc proto-oncogene play a role in transcriptional regulation
      of the prothymosin alpha gene?
AB  - The Myc protein has been reported to activate transcription of the rat
      prothymosin alpha gene by binding to an enhancer element or E box (CACGTG)
      located in the first intron (S. Gaubatz et al., Mol. Cell. Biol. 14:3853-3862,
      1994). The human prothymosin alpha gene contains two such motifs: in the promoter
      region at kb -1.2 and in intron 1, approximately 2 kb downstream of the
      transcriptional start site in a region which otherwise bears little homology to
      the rat gene. Using chloramphenicol acetyltransferase (CAT) reporter constructs
      driven either by the 5-kb human prothymosin alpha promoter or by a series of
      truncated promoters, we showed that removal of the E-box sequence had no effect
      on transient expression of CAT activity in mouse L cells. When intron 1 of the
      prothymosin alpha gene was inserted into the most extensive promoter construct
      downstream of the CAT coding region, a diminution in transcription, which
      remained virtually unchanged upon disruption of the E boxes, was observed. CAT
      constructs driven by the native prothymosin alpha promoter or the native promoter
      and intron were indifferent to Myc; equivalent CAT activity was observed in the
      presence of ectopic normal or mutant Myc genes. Similarly, expression of a
      transiently transfected wild-type prothymosin alpha gene as the reporter was not
      affected by a repertoire of myc-derived genes, including myc itself and dominant
      or recessive negative myc mutants. In COS-1 cells, equivalent amounts of the
      protein were produced from transfected prothymosin alpha genes regardless of
      whether genomic E boxes were disrupted, intron 1 was removed, or a repertoire of
      myc-derived genes was included in the transfection cocktail. More importantly,
      cotransfection of a dominant negative Max gene failed to reduce transcription of
      the endogenous prothymosin alpha gene in COS cells or the wild-type transfected
      gene in COS or L cells. Taken together, the data do not support the idea that Myc
      activates transcription of the intact human prothymosin alpha gene or reporter
      constructs that mimic its structure. Rather, they suggest that the human
      prothymosin alpha promoter and downstream elements are buffered so as to respond
      poorly, if at all, to transient fluctuations in transcription factors which
      regulate other genes.

PMID- 8524268
TI  - The human growth hormone gene is regulated by a multicomponent locus control
      region.
AB  - The five-member human growth hormone (hGH)/chorionic somatomammotropin (hCS) gene
      cluster encodes the pituitary-specific hGH-N gene and four highly related genes
      (hGH-V, hCS-A, hCS-B, and hCS-L) that are expressed only in the placenta. When
      the hGH-N or hCS-A gene, together with all previously identified cis-acting
      regulatory sequences, was integrated into the mouse genome, it was expressed only
      sporadically and at low levels in the transgenic target organs. DNase I mapping
      of chromatin from expressing and nonexpressing cell types was used to identify a
      pituitary-specific set of DNase I-hypersensitive sites (HS) and a set of HS
      common to both the pituitary and placenta, centered approximately 15 and 30 kb 5'
      of hGH-N, respectively. When contained on a cosmid insert in their native genomic
      configuration, these HS consistently directed high-level, pituitary-specific
      expression of hGH-N in transgenic mice and appeared to define a locus control
      region required for hGH-N expression. Individually, each set of HS was able to
      mediate position-independent hGH-N expression in the pituitary but demonstrated
      loss of physiologic control and loss of tissue specificity. The gene-proximal set
      of HS contained a potent enhancer activity in the pituitary, while the more
      distal set appeared to function primarily to establish site-of-integration
      independence. These data indicate that synergistic interactions among multiple
      elements are required to restrict hGH-N transcription to the pituitary and
      generate appropriate levels of expression. In addition, these results suggest a
      role for both shared and unique regulatory sequences in locus control region
      mediated expression of the hGH/hCS gene cluster in the pituitary and possibly the
      placenta.

PMID- 8524269
TI  - A delta T-cell receptor deleting element transgenic reporter construct is
      rearranged in alpha beta but not gamma delta T-cell lineages.
AB  - T cells can be divided into two groups on the basis of the expression of either
      alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain
      locus lies within the larger TCR alpha chain locus, control of the utilization of
      these two receptors is important in T-cell development, specifically for
      determination of T-cell type: rearrangement of the alpha locus results in
      deletion of the delta coding segments and commitment to the alpha beta lineage.
      In the developing thymus, a relative site-specific recombination occurs by which
      the TCR delta chain gene segments are deleted. This deletion removes all D delta,
      J delta, and C delta genes and occurs on both alleles. This delta deletional
      mechanism is evolutionarily conserved between mice and humans. Transgenic mice
      which contain the human delta deleting elements and as much internal TCR delta
      chain coding sequence as possible without allowing the formation of a complete
      delta chain gene were developed. Several transgenic lines showing recombinations
      between deleting elements within the transgene were developed. These lines
      demonstrate that utilization of the delta deleting elements occurs in alpha beta
      T cells of the spleen and thymus. These recombinations are rare in the gamma
      delta population, indicating that the machinery for utilization of delta deleting
      elements is functional in alpha beta T cells but absent in gamma delta T cells.
      Furthermore, a discrete population of early thymocytes containing delta deleting
      element recombinations but not V alpha-to-J alpha rearrangements has been
      identified. These data are consistent with a model in which delta deletion
      contributes to the implementation of a signal by which the TCR alpha chain locus
      is rearranged and expressed and thus becomes an alpha beta T cell.

PMID- 8524270
TI  - Distinct roles for two purified factors in transcription of Xenopus mitochondrial
      DNA.
AB  - Transcription of Xenopus laevis mitochondrial DNA (xl-mtDNA) by the mitochondrial
      RNA polymerase requires a dissociable factor. This factor was purified to near
      homogeneity and identified as a 40-kDa protein. A second protein implicated in
      the transcription of mtDNA, the Xenopus homolog of the HMG box protein mtTFA, was
      also purified to homogeneity and partially sequenced. The sequence of a cDNA
      clone encoding xl-mtTFA revealed a high degree of sequence similarity to human
      and Saccharomyces cerevisiae mtTFA. xl-mtTFA was not required for basal
      transcription from a minimal mtDNA promoter, and this HMG box factor could not
      substitute for the basal factor, which is therefore designated xl-mtTFB. An
      antibody directed against the N terminus of xl-mtTFA did not cross-react with xl
      mtTFB. xl-mtTFA is an abundant protein that appears to have at least two
      functions in mitochondria. First, it plays a major role in packaging mtDNA within
      the organelle. Second, DNase I footprinting experiments identified preferred
      binding sites for xl-mtTFA within the control region of mtDNA next to major
      mitochondrial promoters. We show that binding of xl-mtTFA to a site separating
      the two clusters of bidirectional promoters selectively stimulates specific
      transcription in vitro by the basal transcription machinery, comprising
      mitochondrial RNA polymerase and xl-mtTFB.

PMID- 8524271
TI  - Stimulation of nuclear import by simian virus 40-transformed cell extracts is
      dependent on protein kinase activity.
AB  - We previously reported that both the nuclear import rate of large karyophilic
      gold particles and the functional size of the pores are significantly greater in
      simian virus 40-transformed fibroblasts (the SV-T2 cell line) than in
      nontransformed BALB/c 3T3 cells. In this study, we found that cytosolic fractions
      obtained from SV-T2 cultures can increase nuclear transport capacity (both import
      rate and pore size) when microinjected into BALB/c 3T3 cells. The transport
      enhancing function of the extracts can be abolished by the protein kinase
      inhibitors staurosporine and K252a as well as 5'-p-fluorosulfonylbenzoyladenosine
      and protein phosphatase 2A, which, although less specific, also interfere with
      kinase activity. Increases in transport capacity of the same magnitude as that
      produced by the SV-T2 extracts were obtained by microinjecting protein kinase A
      or C or recombinant mitogen-activated protein kinase. These data provide further
      support for the interpretation that the enhancer is a protein kinase. From
      experiments performed with specific kinase inhibitor peptides, it appears likely
      that protein kinase C is the active factor in the SV-T2 cytosolic fractions;
      however, this will require further verification. It was also determined, by using
      gold particles coated with bovine serum albumin conjugated to synthetic nuclear
      localization signal peptides that lacked phosphorylation sites, that the enhancer
      affects the transport machinery rather than the activity of the nuclear
      localization signals.

PMID- 8524272
TI  - Differential regulation of the alpha/beta interferon-stimulated Jak/Stat pathway
      by the SH2 domain-containing tyrosine phosphatase SHPTP1.
AB  - Interferons (IFNs) induce early-response genes by stimulating Janus family (Jak)
      tyrosine kinases, leading to tyrosine phosphorylation of Stat transcription
      factors. Previous studies implicated protein-tyrosine phosphatase (PTP) activity
      in the control of IFN-regulated Jak/Stat signaling, but the specific PTPs
      responsible remained unidentified. We have found that SH2 domain-containing PTP1
      (SHPTP1; also called PTP1C, HCP, or SHP) reversibly associates with the IFN-alpha
      receptor complex upon IFN addition. Compared with macrophages from normal
      littermate controls, macrophages from motheaten mice, which lack SHPTP1, show
      dramatically increased Jak1 and Stat1 alpha tyrosine phosphorylation, whereas
      Tyk2 and Stat2 activation is largely unaffected. These findings correlate with
      selectively increased complex formation on a gamma response element, but not an
      IFN-stimulated response element, in motheaten macrophages. Our results establish
      that SHPTP1 selectively regulates distinct components of Jak/Stat signal
      transduction pathways in vivo.

PMID- 8524273
TI  - Mechanism of differential utilization of the his3 TR and TC TATA elements.
AB  - The yeast his3 promoter region contains two TATA elements, TC and TR, that are
      differentially utilized in constitutive his3 transcription and Gcn4-activated
      his3 transcription. TR contains the canonical TATAAA sequence, whereas TC is an
      extended region that lacks a conventional TATA sequence and does not support
      transcription in vitro. Surprisingly, differential his3 TATA-element utilization
      does not depend on specific properties of activator proteins but, rather, is
      determined by the overall level of his3 transcription. At low levels of
      transcription, the upstream TC is preferentially utilized, even though it is
      inherently a much weaker TATA element than TR. The TATA elements are utilized
      equally at intermediate levels, whereas TR is strongly preferred at high levels
      of transcription. This characteristic behavior can be recreated by replacing TC
      with moderately functional derivatives of a conventional TATA element, suggesting
      that TC is a collection of weak TATA elements. Analysis of promoters containing
      two biochemically defined TATA elements indicates that differential utilization
      occurs when the upstream TATA element is weaker than the downstream element. In
      other situations, the upstream TATA element is preferentially utilized in a
      manner that is independent of the overall level of transcription. Thus, in
      promoters containing multiple TATA elements, relative utilization not only
      depends on the quality and arrangement of the TATA elements but can vary with the
      overall level of transcriptional stimulation. We suggest that differential TATA
      utilization results from the combination of an intrinsic preference for the
      upstream element and functional saturation of weak TATA elements at low levels of
      transcriptional stimulation.

PMID- 8524274
TI  - The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC
      superfamily involved in DNA repair.
AB  - The rad18 mutant of Schizosaccharomyces pombe is very sensitive to killing by
      both UV and gamma radiation. We have cloned and sequenced the rad18 gene and
      isolated and sequenced its homolog from Saccharomyces cerevisiae, designated
      RHC18. The predicted Rad18 protein has all the structural properties
      characteristic of the SMC family of proteins, suggesting a motor function--the
      first implicated in DNA repair. Gene deletion shows that both rad18 and RHC18 are
      essential for proliferation. Genetic and biochemical analyses suggest that the
      product of the rad18 gene acts in a DNA repair pathway for removal of UV-induced
      DNA damage that is distinct from classical nucleotide excision repair. This
      second repair pathway involves the products of the rhp51 gene (the homolog of the
      RAD51 gene of S. cerevisiae) and the rad2 gene.

PMID- 8524275
TI  - Regulation of the murine alpha B-crystallin/small heat shock protein gene in
      cardiac muscle.
AB  - The murine alpha B-crystallin/small heat shock protein gene is expressed at high
      levels in the lens and at lower levels in the heart, skeletal muscle, and
      numerous other tissues. Previously we have found a skeletal-muscle-preferred
      enhancer at positions -427 to -259 of the alpha B-crystallin gene containing at
      least four cis-acting regulatory elements (alpha BE-1, alpha BE-2, alpha BE-3,
      and MRF, which has an E box). Here we show that in transgenic mice, the alpha B
      crystallin enhancer directs the chloramphenicol acetyltransferase reporter gene
      driven by the alpha B-crystallin promoter specifically to myocardiocytes of the
      heart. The alpha B-crystallin enhancer was active in conjugation with the herpes
      simplex virus thymidine kinase promoter/human growth hormone reporter gene in
      transfected rat myocardiocytes. DNase I footprinting and site-specific
      mutagenesis experiments showed that alpha BE-1, alpha BE-2, alpha BE-3, MRF, and
      a novel, heart-specific element called alpha BE-4 are required for alpha B
      crystallin enhancer activity in transfected myocardiocytes. By contrast, alpha BE
      4 is not utilized for enhancer activity in transfected lens or skeletal muscle
      cell lines. Alpha BE-4 contains an overlapping heat shock sequence and a reverse
      CArG box [5'-GG(A/T)6CC-3']. Electrophoretic mobility shift assays with an
      antibody to serum response factor and a CArG-box-competing sequence from the c
      fos promoter indicated that a cardiac-specific protein with DNA-binding and
      antigenic similarities to serum response factor binds to alpha BE-4 via the
      reverse CArG box; electrophoretic mobility shift assays and antibody experiments
      with anti-USF antiserum and heart nuclear extract also raised the possibility
      that the MRF E box utilizes USF or an antigenically related protein. We conclude
      that the activity of the alpha B-crystallin enhancer in the heart utilizes a
      reverse CArG box and an E-box-dependent pathway.

PMID- 8524276
TI  - The pancreatic islet factor STF-1 binds cooperatively with Pbx to a regulatory
      element in the somatostatin promoter: importance of the FPWMK motif and of the
      homeodomain.
AB  - A number of homeodomain proteins have been shown to regulate cellular development
      by stimulating the transcription of specific target genes. In contrast to their
      distinct activities in vivo, however, most homeodomain proteins bind
      indiscriminately to potential target sites in vitro, suggesting the involvement
      of cofactors which specify target site selection. One such cofactor, termed
      extradenticle, has been shown to influence segmental morphogenesis in Drosophila
      melanogaster by binding cooperatively with certain homeodomain proteins to target
      regulatory elements. Here we demonstrate that STF-1, an orphan homeodomain
      protein required for pancreatic development in mammals, binds cooperatively to
      DNA with Pbx, the mammalian homolog of extradenticle. Cooperative binding with
      Pbx requires a pentapeptide motif (FPWMK) which is well conserved among a large
      subset of homeodomain proteins. The FPMWK motif is not sufficient to confer Pbx
      cooperativity on other homeodomain proteins, however; the N-terminal arm of the
      STF-1 homeodomain is also essential. As cooperative binding with Pbx occurs on
      only a subset of potential STF-1 target sites, our results suggest that Pbx may
      specify target gene selection in the developing pancreas by forming heterodimeric
      complexes with STF-1.

PMID- 8524277
TI  - Mitochondrial GrpE modulates the function of matrix Hsp70 in translocation and
      maturation of preproteins.
AB  - Mitochondrial GrpE (Mge1p) is a mitochondrial cochaperone essential for viability
      of the yeast Saccharomyces cerevisiae. To study the role of Mge1p in the
      biogenesis of mitochondrial proteins, we isolated a conditional mutant allele of
      MGE1 which conferred a temperature-sensitive growth phenotype and led to the
      accumulation of mitochondrial preproteins after shifting of the cells to the
      restrictive temperature. The mutant Mge1 protein was impaired in its interaction
      with the matrix heat shock protein mt-Hsp70. The mutant mitochondria showed a
      delayed membrane translocation of preproteins, and the maturation of imported
      proteins was impaired, as evidenced by the retarded second proteolytic processing
      of a preprotein in the matrix. Moreover, the aggregation of imported proteins was
      decreased in the mutant mitochondria. The mutant Mge1p differentially modulated
      the interaction of mt-Hsp70 with preproteins compared with the wild type,
      resulting in decreased binding to preproteins in membrane transit and enhanced
      binding to fully imported proteins. We conclude that the interaction of Mge1p
      with mt-Hsp70 promotes the progress of the Hsp70 reaction cycle, which is
      essential for import and maturation of mitochondrial proteins.

PMID- 8524278
TI  - Degradation of the proto-oncogene product c-Fos by the ubiquitin proteolytic
      system in vivo and in vitro: identification and characterization of the
      conjugating enzymes.
AB  - The transcription factor c-Fos is a short-lived cellular protein. The levels of
      the protein fluctuate significantly and abruptly during changing
      pathophysiological conditions. Thus, it is clear that degradation of the protein
      plays an important role in its tightly regulated activity. We examined the
      involvement of the ubiquitin pathway in c-Fos breakdown. Using a mutant cell
      line, ts20, that harbors a thermolabile ubiquitin-activating enzyme, E1, we
      demonstrate that impaired function of the ubiquitin system stabilizes c-Fos in
      vivo. In vitro, we reconstituted a cell-free system and demonstrated that the
      protein is multiply ubiquitinated. The adducts serve as essential intermediates
      for degradation by the 26S proteasome. We show that both conjugation and
      degradation are significantly stimulated by c-Jun, with which c-Fos forms the
      active heterodimeric transcriptional activator AP-1. Analysis of the enzymatic
      cascade involved in the conjugation process reveals that the ubiquitin-carrier
      protein E2-F1 and its human homolog UbcH5, which target the tumor suppressor p53
      for degradation, are also involved in c-Fos recognition. The E2 enzyme acts along
      with a novel species of ubiquitin-protein ligase, E3. This enzyme is distinct
      from other known E3s, including E3 alpha/UBR1, E3 beta, and E6-AP. We have
      purified the novel enzyme approximately 350-fold and demonstrated that it is a
      homodimer with an apparent molecular mass of approximately 280 kDa. It contains a
      sulfhydryl group that is essential for its activity, presumably for anchoring
      activated ubiquitin as an intermediate thioester prior to its transfer to the
      substrate. Taken together, our in vivo and in vitro studies strongly suggest that
      c-Fos is degraded in the cell by the ubiquitin-proteasome proteolytic pathway in
      a process that requires a novel recognition enzyme.

PMID- 8524279
TI  - An intramolecular recombination mechanism for the formation of the rRNA gene
      palindrome of Tetrahymena thermophila.
AB  - Large palindromic DNAs are found in a wide variety of eukaryotic cells. In
      Tetrahymena thermophila, a large palindrome is formed from a single rRNA gene
      (rDNA) during nuclear differentiation. We present evidence that a key step in the
      formation of the rDNA palindrome of T. thermophila involves homologous
      intramolecular recombination. Heteroduplex micronuclear rDNA molecules were
      constructed in vitro and microinjected into developing macronuclei, where they
      formed palindromes. Analysis of the resulting palindromes indicated that both
      strands of the microinjected rDNA are used to form the same palindrome. This
      study, together with a previous study (L. F. Yasuda and M.-C. Yao, Cell 67:505
      516, 1991), is the first to define a molecular pathway of palindrome formation.
      The process is initiated by chromosome breakage at sites flanking the
      micronuclear rDNA. An intramolecular recombination reaction, guided by a pair of
      short inverted repeats located at the 5' end of the excised rDNA, covalently
      joins the two strands of micronuclear rDNA in a giant hairpin molecule.
      Bidirectional DNA replication converts the giant hairpin molecule to a
      palindrome. We suggest that the general features of this pathway are applicable
      to palindrome formation in other cell types.

PMID- 8524280
TI  - Overexpression of myogenin in muscles of transgenic mice: interaction with Id-1,
      negative crossregulation of myogenic factors, and induction of extrasynaptic
      acetylcholine receptor expression.
AB  - To investigate the role of myogenin in regulating acetylcholine receptor
      expression in adult muscle, this muscle-specific basic helix-loop-helix
      transcription factor was overexpressed in transgenic mice by using regulatory
      elements conferring strong expression confined to differentiated postmitotic
      muscle fibers. Many of the transgenic mice died during the first postnatal week,
      but those that survived into adulthood displayed normal muscle histology, gross
      morphology, and motor behavior. The mRNA levels of all five acetylcholine
      receptor subunits (alpha, beta, gamma, delta, and epsilon) were, however,
      elevated. Also, the level of receptor protein was increased and high levels of
      receptors were present throughout the extrasynaptic surface membrane of the
      muscle fibers. Thus, elevated levels of myogenin are apparently sufficient to
      induce acetylcholine supersensitivity in normally innervated muscle of adult
      mice. The high neonatal mortality rate of the mice overexpressing myogenin
      hindered the propagation of a stable line. In an attempt to increase survival,
      myogenin overexpressers were mated with a line of transgenic mice overexpressing
      Id-1, a negative regulator that interacts with the basic helix-loop-helix family
      of transcription factors. The Id-1 transgene apparently worked as a second site
      suppressor and abolished the high rate of neonatal mortality. This effect
      indicates that Id-1 and myogenin interact directly or indirectly in these
      animals. Further study indicated that myogenin overexpression had no effect on
      the level of endogenous myogenin mRNA, while the levels of myoD and MRF4 mRNAs
      were reduced. Overexpression of the negative regulator Id-1 increased the mRNA
      levels of all the myogenic factors. These findings are consistent with a
      hypothesis suggesting that myogenic factors are influenced by mechanisms that
      maintain cellular homeostasis.

PMID- 8524281
TI  - An intron enhancer containing a 5' splice site sequence in the human
      calcitonin/calcitonin gene-related peptide gene.
AB  - Regulation of calcitonin (CT)/calcitonin gene-related peptide (CGRP) RNA
      processing involves the use of alternative 3' terminal exons. In most tissues and
      cell lines, the CT terminal exon is recognized. In an attempt to define
      regulatory sequences involved in the utilization of the CT-specific terminal
      exon, we performed deletion and mutation analyses of a mini-gene construct that
      contains the CT terminal exon and mimics the CT processing choice in vivo. These
      studies identified a 127-nucleotide intron enhancer located approximately 150
      nucleotides downstream of the CT exon poly(A) cleavage site that is required for
      recognition of the exon. The enhancer contains an essential and conserved 5'
      splice site sequence. Mutation of the splice site resulted in diminished
      utilization of the CT-specific terminal exon and increased skipping of the CT
      exon in both the mini-gene and in the natural CT/CGRP gene. Other components of
      the intron enhancer modified utilization of the CT-specific terminal exon and
      were necessary to prevent utilization of the 5' splice site within the intron
      enhancer as an actual splice site directing cryptic splicing. Conservation of the
      intron enhancer in three mammalian species suggests an important role for this
      intron element in the regulation of CT/CGRP processing and an expanded role for
      intronic 5' splice site sequences in the regulation of RNA processing.

PMID- 8524282
TI  - Plk is an M-phase-specific protein kinase and interacts with a kinesin-like
      protein, CHO1/MKLP-1.
AB  - PLK (STPK13) encodes a murine protein kinase closely related to those encoded by
      the Drosophila melanogaster polo gene and the Saccharomyces cerevisiae CDC5 gene,
      which are required for normal mitotic and meiotic divisions. Affinity-purified
      antibody generated against the C-terminal 13 amino acids of Plk specifically
      recognizes a single polypeptide of 66 kDa in MELC, NIH 3T3, and HeLa cellular
      extracts. The expression levels of both poly(A)+ PLK mRNA and its encoded protein
      are most abundant about 17 h after serum stimulation of NIH 3T3 cells. Plk
      protein begins to accumulate at the S/G2 boundary and reaches the maximum level
      at the G2/M boundary in continuously cycling cells. Concurrent with cyclin B
      associated cdc2 kinase activity, Plk kinase activity sharply peaks at the onset
      of mitosis. Plk enzymatic activity gradually decreases as M phase proceeds but
      persists longer than cyclin B-associated cdc2 kinase activity. Plk is localized
      to the area surrounding the chromosomes in prometaphase, appears condensed as
      several discrete bands along the spindle axis at the interzone in anaphase, and
      finally concentrates at the midbody during telophase and cytokinesis. Plk and
      CHO1/mitotic kinesin-like protein 1 (MKLP-1), which induces microtubule bundling
      and antiparallel movement in vitro, are colocalized during late M phase. In
      addition, CHO1/MKLP-1 appears to interact with Plk in vivo and to be
      phosphorylated by Plk-associated kinase activity in vitro.

PMID- 8524283
TI  - Gas1-induced growth suppression requires a transactivation-independent p53
      function.
AB  - In normal cells, induction of quiescence is accompanied by the increased
      expression of growth arrest-specific genes (gas). One of them, gas1, is regulated
      at the transcriptional level and codes for a membrane-associated protein (Gas1)
      which is down regulated during the G0-to-S phase transition in serum-stimulated
      cells. Gas1 is not expressed in growing or transformed cells, and when
      overexpressed in normal fibroblasts, it blocks the G0-to-S phase transition.
      Moreover, Gas1 blocks cell proliferation in several transformed cells with the
      exception of simian virus 40- or adenovirus-transformed cell lines. In this
      paper, we demonstrate that overexpression of Gas1 blocks cell proliferation in a
      p53-dependent manner and that the N-terminal domain-dependent transactivating
      function of p53 is dispensable for Gas1-induced growth arrest. These data
      therefore indicate that the other intrinsic transactivation-independent functions
      of p53, possibly related to regulation of apoptosis, should be involved in
      mediating Gas1-induced growth arrest.

PMID- 8524284
TI  - Cloning of two proximal sequence element-binding transcription factor subunits
      (gamma and delta) that are required for transcription of small nuclear RNA genes
      by RNA polymerases II and III and interact with the TATA-binding protein.
AB  - The proximal sequence element (PSE)-binding transcription factor (PTF)
      specifically recognizes the PSEs of both RNA polymerase II- and RNA polymerase
      III-transcribed small nuclear RNA (snRNA) genes. We previously have shown that
      PTF purified from human HeLa cells is a multisubunit complex of four polypeptides
      designated PTF alpha, -beta, -gamma, and -delta. We now report the isolation and
      expression of cDNAs encoding PTF gamma and PTF delta, as well as functional
      studies with cognate antibodies that recognize the native PTF complex in HeLa
      extracts. Immunoprecipitation studies confirm that the four PTF subunits
      originally found to copurify during conventional chromatography indeed form a
      tightly associated complex; they further show that the PTF so defined, including
      the gamma and delta subunits specifically, is essential for transcription of both
      class II and class III snRNA genes. Immunoprecipitation assays also show a weak
      substoichiometric association of the TATA-binding protein (TBP) with PTF,
      consistent with the previous report of a PTF-related complex (SNAPc) containing
      substoichiometric levels of TBP and a component (SNAPc43) identical in sequence
      to the PTF gamma reported here. Glutathione S-transferase pulldown assays further
      indicate relatively strong direct interactions of both recombinant PTF gamma and
      PTF delta with TBP, consistent either with the natural association of TBP with
      PTF in a semistable TBP-TBP-associated factor complex or with possible functional
      interactions between PSE-bound PTF and TATA-bound TBP during promoter activation.
      In addition, we show that in extracts depleted of TBP and TBP-associated factors,
      transcription from the U1 promoter is restored by recombinant TBP but not by
      TFIID or TFIIIB, indicating that transcription of class II snRNA genes requires a
      TBP complex different from the one used for mRNA-encoding genes.

PMID- 8524285
TI  - High-frequency illegitimate integration of transfected DNA at preintegrated
      target sites in a mammalian genome.
AB  - To examine the mechanisms of recombination governing the illegitimate integration
      of transfected DNA into a mammalian genome, we developed a cell system that
      selects for integration events in defined genomic regions. Cell lines with
      chromosomal copies of the 3' portion of the adenine phosphoribosyltransferase
      (APRT) gene (targets) were established. The 5' portion of the APRT gene, which
      has no homology to the integrated 3' portion, was then electroporated into the
      target cell lines, and selection for APRT gene function was applied. The
      reconstruction of the APRT gene was detected at frequencies ranging from less
      than 10(-7) to 10(-6) per electroporated cell. Twenty-seven junction sequences
      between the integrated 5' APRT and its chromosomal target were analyzed. They
      were found to be randomly distributed in a 2-kb region immediately in front of
      the 3' portion of the APRT gene. The junctions fell into two main classes: those
      with short homologies (microhomologies) and those with inserted DNA of uncertain
      origin. Three long inserts were shown to preexist elsewhere in the genome.
      Reconstructed cell lines were analyzed for rearrangements at the target site by
      Southern blotting; a variety of simple and complex rearrangements were detected.
      Similar analysis of individual clones of the parental cell lines revealed
      analogous types of rearrangement, indicating that the target sites are unstable.
      Given the high frequency of integration events at these sites, we speculate that
      transfected DNA may preferentially integrate at unstable mammalian loci. The
      results are discussed in relation to possible mechanisms of DNA integration.

PMID- 8524286
TI  - Lambda-interacting protein, a novel protein that specifically interacts with the
      zinc finger domain of the atypical protein kinase C isotype lambda/iota and
      stimulates its kinase activity in vitro and in vivo.
AB  - The members of the atypical subfamily of protein kinase C (PKC) show dramatic
      structural and functional differences from other PKC isotypes. Thus, in contrast
      to the classical or novel PKCs, they are not activated by diacylglycerol or
      phorbol esters. However, the atypical PKCs are the target of important lipid
      second messengers such as ceramide, phosphatidic acid, and 3'-phosphoinositides.
      The catalytic and pseudosubstrate sequences in the two atypical PKCs (lambda/iota
      PKC and zeta PKC) are identical but are significantly different from those of
      conventional or novel PKCs. It has been shown that microinjection of a peptide
      with the sequence of the pseudosubstrate of the atypical PKC isotypes but not of
      alpha PKC or epsilon PKC dramatically inhibited maturation and NF-kappa B
      activation in Xenopus oocytes, as well as reinitiation of DNA synthesis in
      quiescent mouse fibroblasts. This indicates that either or both atypical isoforms
      are important in cell signalling. Besides the pseudosubstrate, the major
      differences in the sequence between lambda/iota PKC and zeta PKC are located in
      the regulatory domain. Therefore, any functional divergence between the two types
      of atypical PKCs will presumably reside in that region. We report here the
      molecular characterization of lambda-interacting protein (LIP), a novel protein
      that specifically interacts with the zinc finger of lambda/iota PKC but not zeta
      PKC. We show in this paper that this interaction is detected not only in vitro
      but also in vivo, that LIP activates lambda/iota PKC but not zeta PKC in vitro
      and in vivo, and that this interaction is functionally relevant. Thus, expression
      of LIP leads to the transactivation of a kappa B-dependent promoter in a manner
      that is dependent on lambda/iota PKC. To our knowledge, this is the first report
      on the cloning and characterization of a protein activator of a PKC that binds to
      the zinc finger domain, which has so far been considered a site for binding of
      lipid modulators. The fact that LIP binds to lambda/iota PKC but not to the
      highly related zeta PKC isoform suggests that the specificity of the activation
      of the members of the different PKC subfamilies will most probably be accounted
      for by proteins like LIP rather than by lipid activators.

PMID- 8524287
TI  - SSN genes that affect transcriptional repression in Saccharomyces cerevisiae
      encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II.
AB  - The RNA polymerase II of Saccharomyces cerevisiae exists in holoenzyme forms
      containing a complex, known as the mediator, associated with the carboxyl
      terminal domain. The mediator includes several SRB proteins and is required for
      transcriptional activation. Previous work showed that a cyclin-dependent kinase
      cyclin pair encoded by SSN3 and SSN8, two members of the SSN suppressor family,
      are identical to two SRB proteins in the mediator. Here we have identified the
      remaining SSN genes by cloning and genetic analysis. SSN2 and SSN5 are identical
      to SRB9 and SRB8, respectively, which encode additional components of the
      mediator. Genetic evidence implicates the SSN genes in transcriptional
      repression. Thus, these identities provide genetic insight into mediator and
      carboxyl-terminal domain function, strongly suggesting a role in mediating
      transcriptional repression as well as activation. We also show that SSN4 and SSN7
      are the same as SIN4 and ROX3, respectively, raising the possibility that these
      genes also encode mediator proteins.

PMID- 8524288
TI  - The AD1 transactivation domain of E2A contains a highly conserved helix which is
      required for its activity in both Saccharomyces cerevisiae and mammalian cells.
AB  - A conserved region, designated the AD1 domain, is present in a class of helix
      loop-helix (HLH) proteins, E proteins, that includes E12, E47, HEB, E2-2, and a
      Xenopus laevis HLH protein closely related to E12. We demonstrate that the AD1
      domain in E2A and the conserved region of E2-2 activate transcription in both
      yeast and mammalian cells. The AD1 domain contains a highly conserved putative
      helix that is crucial for its transactivation properties. Circular dichroism
      spectroscopy data show that AD1 is structured and contains distinctive helical
      properties. In addition, we show that a synthetic peptide corresponding to the
      conserved region is unstructured in aqueous solution at neutral pH but can adopt
      an alpha-helical conformation in the presence of the hydrophobic solvent
      trifluoroethanol. Amino acid substitutions that destabilize the helix abolish the
      transactivation ability of the AD1 domain. Both structural and functional
      analyses of AD1 reveal striking similarities to the acidic class of activators.
      Remarkably, when wild-type and mutant proteins are expressed in mammalian cells
      and Saccharomyces cerevisiae, identical patterns of transactivation are observed,
      suggesting that the target molecule is conserved between S. cerevisiae and
      mammals. These data show that transactivation by E proteins is mediated, in part,
      by a strikingly conserved peptide that has the ability to form a helix in a
      hydrophobic solvent. We propose that the unstructured domain may become helical
      upon interaction with its cellular target molecule.

PMID- 8524289
TI  - A newly formed telomere in Ascaris suum does not exert a telomere position effect
      on a nearby gene.
AB  - During the process of chromatin diminution in Ascaris suum (formerly named
      Ascaris lumbricoides var. suum), developmentally regulated chromosomal
      fragmentation and new telomere addition occur within specific chromosomal
      breakage regions (CBRs). The DNA sequences flanking one of these CBRs (CBR-1)
      were analyzed, and two protein-encoding genes were found on either side. The
      noneliminated gene, agp-1, whose AUG start codon is located within approximately
      2 kb of the boundary of CBR-1, encodes a putative GTP-binding protein which is
      structurally related to eukaryotic and prokaryotic elongation factors. Northern
      (RNA) blot analyses revealed that transcripts of this gene are present at all
      developmental stages, suggesting that the massive chromosomal rearrangements
      associated with the process of chromatin diminution have no influence on agp-1
      expression. This demonstrates that addition of new telomeres in CBR-1 does not
      result in a telomeric position effect, a phenomenon previously described in
      Saccharomyces cerevisiae.

PMID- 8524291
TI  - Translational efficiency is regulated by the length of the 3' untranslated
      region.
AB  - All polyadenylated mRNAs contain sequence of variable length between the coding
      region and the poly(A) tail. Little has been done to establish what role the
      length of the 3' untranslated region (3'UTR) plays in posttranscriptional
      regulation. Using firefly luciferase (luc) reporter mRNA in transiently
      transfected Chinese hamster ovary (CHO) cells, we observed that the addition of a
      poly(A) tail increased expression 97-fold when the length of the 3'UTR was 19
      bases but that its stimulatory effect was only 2.3-fold when the length of the
      3'UTR was increased to 156 bases. The effect of the luc 3'UTR on poly(A) tail
      function was orientation independent, suggesting that its length and not its
      primary sequence was the important factor. Increasing the length of the 3'UTR
      increased expression from poly(A)- mRNA but had little effect on poly(A)+ mRNA.
      To examine the effect of length on translational efficiency and mRNA stability, a
      20-base sequence was introduced and reiterated downstream of the luc stop codon
      to generate a nested set of constructs in which the length of the 3'UTR increased
      from 4 to 104 bases. For poly(A)- reporter mRNA, translational efficiency in CHO
      cells increased 38-fold as the length of the 3'UTR increased from 4 to 104 bases.
      Increasing the length of the 3'UTR beyond 104 bases increased expression even
      further. Increasing the length of the 3'UTR also resulted in a 2.5-fold
      stabilization of the reporter mRNA. For poly(A)+ mRNA, the translational
      efficiency and mRNA half-life increased only marginally as the length of the
      3'UTR increased from 27 to 161 bases. However, positioning the poly(A) tail only
      7 bases downstream of the stop codon resulted in a 39-fold reduction in the rate
      of translation relative to a construct with a 27-base 3'UTR, which may be a
      consequence of the poly(A) tail-poly(A)-binding protein complex functioning as a
      steric block to translocating ribosomes as they approached the termination codon.
      The optimal length of the 3' noncoding region for maximal poly(A) tail-mediated
      stimulation of translation is approximately 27 bases. These data suggest that the
      length of the 3'UTR plays an important role in determining both the translational
      efficiency and the stability of an mRNA.

PMID- 8524290
TI  - Differential activation of the Ras/extracellular-signal-regulated protein kinase
      pathway is responsible for the biological consequences induced by the Axl
      receptor tyrosine kinase.
AB  - To understand the mechanism of Axl signaling, we have initiated studies to
      delineate downstream components in interleukin-3-dependent 32D cells by using a
      chimeric receptor containing the recombinant epidermal growth factor (EGF)
      receptor extracellular and transmembrane domains and the Axl kinase domain (EAK
      [for EGF receptor-Axl kinase]). We have previously shown that upon exogenous EGF
      stimulation, 32D-EAK cells are capable of proliferation in the absence of
      interleukin-3. With this system, we determined that EAK-induced cell survival and
      mitogenesis are dependent upon the Ras/extracellular-signal-regulated protein
      kinase (ERK) cascade. Although the phosphatidylinositol-3 kinase pathway is
      activated upon EAK signaling, it appears to be dispensable for the biological
      actions of the Axl kinase. Furthermore, we demonstrated that different threshold
      levels of Ras/ERK activation are needed to induce a block to apoptosis or
      proliferation in 32D cells. Recently, we have identified an Axl ligand, GAS6.
      Surprisingly, GAS6-stimulated 32D-Axl cells exhibited no blockage to apoptosis or
      mitogenic response which is correlated with the absence of Ras/ERK activation.
      Taken together, these data suggest that different extracellular domains
      dramatically alter the intracellular response of the Axl kinase. Furthermore, our
      data suggest that the GAS6-Axl interaction does not induce mitogenesis and that
      its exact role remains to be determined.

PMID- 8524292
TI  - Characterization of the human granulocyte-macrophage colony-stimulating factor
      gene promoter: an AP1 complex and an Sp1-related complex transactivate the
      promoter activity that is suppressed by a YY1 complex.
AB  - It is well documented that a repeated CATT element in the human granulocyte
      macrophage colony-stimulating factor (GM-CSF) gene promoter is required for
      promoter activity. However, the transcription factors that are able to
      transactivate this enhancer element remain unidentified. Recently, we have found
      that nuclear factor YY1 can interact with the enhancer element. Here, we report
      that in addition to YY1, two other nuclear factors have been identified in the
      DNA-protein complexes formed by the CATT oligonucleotide and the Jurkat T-cell
      nuclear protein. One of these factors is AP1, and the other one is an Sp1-related
      protein. Results from transient transfection of Jurkat T cells have revealed that
      formation of both AP1 and the Sp1-related complex is required for the full
      enhancer activity of the CATT element. This result is supported by cotransfection
      of a c-jun expression vector and mutational analysis of the AP1 site or the Sp1
      related protein binding site. In contrast, formation of the YY1 complex
      suppresses enhancer activity, since deletion of the YY1 complex induces an
      augmentation of the enhancer activity and overexpression of YY1 results in an
      attenuation of the enhancer activity. Results from the mechanism study have
      revealed that YY1 is able to inhibit transactivation mediated by either AP1 or
      the Sp1-related protein, and YY1 suppressive activity is DNA binding dependent.
      Taken together, these data support the ideas that AP1 and the Sp1-related nuclear
      protein are required for transactivation of the human GM-CSF gene promoter and
      that YY1 can suppress transactivation of the promoter even under inducible
      conditions.

PMID- 8524293
TI  - Interactions between the ankyrin repeat-containing protein Akr1p and the
      pheromone response pathway in Saccharomyces cerevisiae.
AB  - Akr1p, which contains six ankyrin repeats, was identified during a screen for
      mutations that displayed synthetic lethality with a mutant allele of the bud
      emergence gene BEM1. Cells from which AKR1 had been deleted were alive but
      misshapen at 30 degrees C and inviable at 37 degrees C. During a screen for
      mutants that required one or more copies of wild-type AKR1 for survival at 30
      degrees C, we isolated mutations in GPA1, which encodes the G alpha subunit of
      the pheromone receptor-coupled G protein. (The active subunit of this G protein
      is G beta gamma, and G alpha plays an inhibitory role in G beta gamma-mediated
      signal transduction.) AKR1 could serve as a multicopy suppressor of the lethality
      caused by either loss of GPA1 or overexpression of STE4, which encodes the G beta
      subunit of this G protein, suggesting that pheromone signaling is inhibited by
      overexpression of Akr1p. Mutations in AKR1 displayed synthetic lethality with a
      weak allele of GPA1 and led to increased expression of the pheromone-inducible
      gene FUS1, suggesting that Akr1p normally (and not just when overexpressed)
      inhibits signaling. In contrast, deletion of BEM1 resulted in decreased
      expression of FUS1, suggesting that Bem1p normally facilitates pheromone
      signaling. During a screen for proteins that displayed two-hybrid interactions
      with Akr1p, we identified Ste4p, raising the possibility that an interaction
      between Akr1p and Ste4p contributes to proper regulation of the pheromone
      response pathway.

PMID- 8524294
TI  - Schizosaccharomyces pombe skp1+ encodes a protein kinase related to mammalian
      glycogen synthase kinase 3 and complements a cdc14 cytokinesis mutant.
AB  - We report the cloning of the skp1+ gene, a Schizosaccharomyces pombe homolog of
      the glycogen synthase kinase 3 (GSK-3) family whose members in higher eukaryotes
      are involved in cell fate determination, nuclear signalling, and hormonal
      regulation. skp1 is 67% identical to mammalian GSK-3 beta and displays similar
      biochemical properties in vitro. Like GSK-3 beta, skp1 is phosphorylated on a
      conserved tyrosine residue, and this phosphorylation is required for efficient
      activity. skp1 is also phosphorylated at a serine which has been identified as S
      335. Phosphorylation at this site is likely to inhibit its function. Unlike the
      mammalian enzyme, skp1 both tyrosine autophosphorylates in yeast cells and can
      phosphorylate other proteins on tyrosine in bacteria. The skp1+ gene is not
      essential. However, cells with deletions in skp1+ are sensitive to heat shock and
      exhibit defects in sporulation. Overexpression of wild-type skp1+ specifically
      complements cdc14-118, one of several mutations causing a defect in cytokinesis.
      In addition, certain phosphorylation site mutants induce a delay or block in
      cytokinesis when overexpressed. Together, these data identify novel interactions
      of a fission yeast GSK-3 homolog with elements of the cytokinesis machinery.

PMID- 8524295
TI  - Activation of proglucagon gene transcription through a novel promoter element by
      the caudal-related homeodomain protein cdx-2/3.
AB  - The proglucagon gene is expressed in a highly restricted tissue-specific manner
      in the A cells of the pancreatic islet and the L cells of the small and large
      intestines. The results of previous experiments indicate that cell-specific
      expression of the proglucagon gene is mediated by proteins that interact with the
      proximal G1 promoter element. We show here that the G1 element contains several
      AT-rich subdomains that bind proteins present in islet and enteroendocrine cell
      extracts. Electrophoretic mobility shift assay experiments using specific
      antisera identified the homeobox protein cdx-2/3 (which designates the same
      homeobox protein called cdx-2 for mice and cdx-3 for hamsters) as a major
      component of the G1-Gc2 complex in islet and intestinal cells. Mutations of the
      Gc element that decreased cdx-2/3 binding also resulted in decreased proglucagon
      promoter activity in islet and intestinal cell lines. The finding that cdx-2/3
      mediates activation of the proglucagon promoter in both islet and enteroendocrine
      cells is consistent with the common endodermal lineage of these tissues and
      provides new insight into the coordinate regulation of genes expressed in both
      pancreatic and intestinal endocrine cell types.

PMID- 8524296
TI  - A homolog of human transcription factor NF-X1 encoded by the Drosophila shuttle
      craft gene is required in the embryonic central nervous system.
AB  - NF-X1 is a novel cytokine-inducible transcription factor that has been implicated
      in the control of immune responses in humans, presumably by regulating expression
      of class II major histocompatibility genes. Here we report the cloning and
      genetic characterization of the first reported NF-X1 homolog, which is encoded by
      the Drosophila melanogaster shuttle craft (stc) gene. The deduced sequence of the
      fly and human proteins defines a new family of molecules distinguished by a novel
      cysteine-rich DNA-binding motif (consisting of seven copies of the consensus
      sequence Cx3Cx3LxCGx0-5HxCx3CHxGxCx2Cx7-9CxC). We have identified and begun a
      phenotypic characterization of mutations in the stc gene. stc mutants die at the
      end of embryogenesis, when they appear to be incapable of coordinating the
      typical peristaltic contraction waves normally required for embryos to hatch into
      feeding first instar larvae. Preliminary evidence indicates that the resulting
      lethality of this behavioral defect is accompanied by subtle morphological
      abnormalities in the central nervous system, where in wild-type embryos, STC
      protein is normally localized in the nuclei of repeated cell clusters within each
      neuromere and brain lobe. Thus, the NF-X1 homolog encoded by the Drosophila stc
      gene defines a new family of putative transcription factors and plays an
      essential role in the completion of embryonic development. This study presents
      the first in vivo genetic analysis of a member of this new protein family.

PMID- 8524297
TI  - Kinetics of transcription factors regulating the RANTES chemokine gene reveal a
      developmental switch in nuclear events during T-lymphocyte maturation.
AB  - RANTES is a chemoattractant cytokine (chemokine) whose gene is expressed
      immediately after stimulation of several cell types but upregulated late (3 to 5
      days) after activation in normal T lymphocytes. Here we describe two cis-acting
      elements in the human RANTES promoter that act in T lymphocytes. One site
      interacts with NFIL6, which is activated within the first 24 h after T-cell
      activation. The second site binds an apparently novel complex that is upregulated
      later, between days 3 and 5. These data provide an explanation for the immediate
      early expression of RANTES in some cell types and identify apparently novel
      factors contributing to late RANTES transcription in T cells. The results reveal
      a developmental switch occurring during normal T-cell maturation coincident with
      the onset of terminal differentiation and the binding of late-acting factors to
      sequences of the RANTES promoter.

PMID- 8524298
TI  - Induction of apoptosis by c-Fos protein.
AB  - The role of c-Fos in apoptosis was examined in two Syrian hamster embryo cell
      lines (sup+I and sup-II) and a human colorectal carcinoma cell line (RKO), using
      the chimeric Fos-estrogen receptor fusion protein c-FosER. As previously
      reported, contrasting responses were observed when these two cell lines were
      placed under growth factor deprivation conditions; sup+I cells were highly
      susceptible to apoptosis, whereas sup-II cells were resistant. In this report, we
      show that the activated c-FosER protein induces apoptosis in sup-II preneoplastic
      cells in serum-free medium, indicating that c-Fos protein can induce apoptotic
      cell death in these cells. c-Fos-induced apoptosis was not blocked by the protein
      synthesis inhibitor cycloheximide, suggesting that the c-Fos transcriptional
      activation activity is not involved. This conclusion was further supported by the
      observation that overexpression of v-Fos, which is highly proficient in
      transcriptional activation but deficient in the transcriptional repression
      activity associated with c-Fos, did not induce apoptosis. Constitutively
      expressed Bcl-2 delayed the onset of low-serum-induced apoptosis in sup+I cells
      and enhanced survival in sup-II cells. Further, coexpression of Bcl-2 and c-FosER
      in sup+I or sup-II cells protected the cells from c-FosER-induced apoptosis. The
      possibility that c-FosER-induced apoptosis requires a p53 function was examined.
      Colorectal carcinoma RKOp53+/+ cells, which do not normally undergo apoptosis in
      serum-free medium, showed apoptotic DNA fragmentation upon expression and
      activation of c-FosER. Further, when the wild-type p53 protein was diminished in
      the RKO cells by infection with the papillomavirus E6 gene, subsequent c-FosER
      induced apoptosis was blocked. The data suggest that c-Fos protein plays a causal
      role in the activation of apoptosis in a p53-dependent manner. This activity does
      not require new protein synthesis and is blocked by overexpression of Bcl-2
      protein.

PMID- 8524299
TI  - A shift in the ligand responsiveness of thyroid hormone receptor alpha induced by
      heterodimerization with retinoid X receptor alpha.
AB  - Thyroid hormone (T3) receptors (T3Rs) are ligand-modulated transcription factors
      that bind to thyroid hormone response elements (T3REs) and mediate either
      positive or negative transcriptional regulation of target genes. In addition, in
      response to ligand binding, T3Rs can interfere with AP-1 activity and thereby
      inhibit transcription of AP-1-responsive genes. T3Rs were recently shown to form
      heterodimers with retinoid X receptors (RXRs), leading to increased binding to
      T3REs in vitro and potentiation of transcriptional responses in vivo. Here we
      demonstrate that T3R alpha forms stable heterodimers with RXR alpha in living
      cells. Most important, we describe a new role for RXR alpha in modulating ligand
      dependent T3R alpha activity: heterodimerization with RXR alpha greatly increases
      transcriptional interference with AP-1 activity, augments T3-dependent
      transcriptional activation, and potentiates the reversal of ligand-independent
      activation by T3R alpha. In all three cases, the responses occur at substantially
      lower T3 concentrations when elicited by T3R alpha plus RXR alpha than by T3R
      alpha alone. In vitro, the binding of T3 decreases the DNA-binding activity of
      T3R alpha homodimers but does not affect DNA binding by T3R alpha:RXR alpha
      heterodimers. We provide evidence that increased activities of T3R alpha at lower
      T3 concentrations are not due to changes in its T3 binding properties. Instead,
      the altered response could be mediated by either RXR alpha-induced conformational
      changes, increased stability of heterodimers over homodimers, especially
      following T3 binding, or both.

PMID- 8524300
TI  - Nuclear factor of activated T cells is associated with a mast cell interleukin 4
      transcription complex.
AB  - Interleukin 4 (IL-4), an immunoregulatory cytokine, is produced only by a subset
      of activated T cells and cells of the mast cell-basophil lineage. The production
      of IL-4 by mast cells likely represents a significant source of this protein in
      local immune-inflammatory responses in the skin, brain, gastrointestinal, and
      respiratory tracts, in which mast cells are prevalent. In the present study, the
      cis- and trans-acting elements that control inducible mast cell IL-4 gene
      transcription were examined and compared with those that function in T cells. We
      demonstrate that, as in T cells, sequences between bp -87 and -70 are critical
      for protein association and activation-dependent gene transcription and that this
      region (termed the activation-responsive element region) is the target of an
      inducible, cyclosporin A-sensitive, DNA-protein interaction. When assessed by
      electrophoretic mobility shift assays and UV cross-linking analyses, multiple
      proteins in both T- and mast cell nuclear extracts associate with the activation
      responsive element in vitro, and some of these appear identical. However,
      distinct proteins are associated with each of the complexes as well. AP-1 family
      members are unique to the T-cell-stimulation-dependent complex, whereas mast cell
      complexes contain factors that are reactive with anti-nuclear factor of activated
      T cells p (NF-ATp) and anti-NF-ATc antibodies but have distinct molecular masses
      compared with those of T-cell-derived NF-AT. Furthermore, an anti-NF-ATp-reactive
      factor with a molecular mass of approximately 41 kDa is present in the nuclei of
      unstimulated cells and binds independently of cell activation, unlike the
      previously described NF-AT family members. These data support the idea that there
      are uniquely regulated, cell lineage-specific transcription factors related to T
      cell-derived NF-AT that mediate inducible IL-4 transcription in mast cells. These
      differences likely reflect the distinct cell surface signaling requirements for
      IL-4 production in T and mast cells.

PMID- 8524301
TI  - Intronic and flanking sequences are required to silence enhancement of an
      embryonic beta-type globin gene.
AB  - In the course of studying regulatory elements that affect avian embryonic rho
      globin gene expression, the multipotential hematopoietic cell line K562 was
      transiently transfected with various rho-globin gene constructs containing or
      lacking an avian erythroid enhancer element. Enhanced levels of rho gene
      expression were seen from those constructs containing an enhancer element and
      minimal 5' or 3' flanking rho sequences but were not seen from enhancer
      containing constructs that included extensive 5' and 3' flanking sequences.
      Deletion analysis localized 5' and 3' "enhancer-silencing elements" to -2140 to 
      2000 and +1865 to +2180 relative to the mRNA cap site. A third element required
      for enhancer silencing was identified within the second intron of the rho gene.
      The treatment of K562 cells with hemin, which induces erythroid differentiation,
      partially alleviated the enhancer-silencing effect. The silencer elements were
      able to block enhancement from a murine erythroid enhancer, but not from a
      nonerythroid enhancer. Electrophoretic mobility shift assays demonstrated that
      the transcription factor YY1 is able to bind both the 5' and 3' enhancer silencer
      elements; a point mutation of the single overlapping YY1/NF-Y binding site in the
      3' element completely abolished the enhancer-silencing effect. These results
      demonstrate a complex enhancer silencer that requires 5' flanking, intronic, and
      3' flanking sequences for a single regulatory effect on a eukaryotic gene.

PMID- 8524302
TI  - Regulation of the G-protein-coupled alpha-factor pheromone receptor by
      phosphorylation.
AB  - The alpha-factor pheromone receptor activates a G protein signaling cascade that
      stimulates MATa yeast cells to undergo conjugation. The cytoplasmic C terminus of
      the receptor is not necessary for G protein activation but instead acts as a
      regulatory domain that promotes adaptation to alpha-factor. The role of
      phosphorylation in regulating the alpha-factor receptor was examined by mutating
      potential phosphorylation sites. Mutation of the four most distal serine and
      threonine residues in the receptor C terminus to alanine caused increased
      sensitivity to alpha-factor and a delay in recovering from a pulse of alpha
      factor. 32PO4 labeling experiments demonstrated that the alanine substitution
      mutations decreased the in vivo phosphorylation of the receptor. Phosphorylation
      apparently alters the regulation of G protein activation, since neither receptor
      number nor affinity for ligand was significantly altered by mutation of the
      distal phosphorylation sites. Furthermore, mutation of the distal phosphorylation
      sites in a receptor mutant that fails to undergo ligand-stimulated endocytosis
      caused increased sensitivity to alpha-factor, which suggests that regulation by
      phosphorylation can occur at the cell surface and is independent of endocytosis.
      Mutation of the distal serine and threonine residues of the receptor also caused
      a slight defect in alpha-factor-induced morphogenesis, but the defect was not as
      severe as the morphogenesis defect caused by truncation of the cytoplasmic C
      terminus of the receptor. These distal residues in the C terminus play a special
      role in receptor regulation, since mutation of the next five adjacent serine and
      threonine residues to alanine did not affect the sensitivity to alpha-factor.
      Altogether, these results indicate that phosphorylation plays an important role
      in regulating alpha-factor receptor function.

PMID- 8524303
TI  - Mechanistic constraints on diversity in human V(D)J recombination.
AB  - We have analyzed a large collection of coding junctions generated in human cells.
      From this analysis, we infer the following about nucleotide processing at coding
      joints in human cells. First, the pattern of nucleotide loss from coding ends is
      influenced by the base composition of the coding end sequences. AT-rich sequences
      suffer greater loss than do GC-rich sequences. Second, inverted repeats can occur
      at ends that have undergone nucleolytic processing. Previously, inverted repeats
      (P nucleotides) have been noted only at coding ends that have not undergone
      nucleolytic processing, this observation being the basis for a model in which a
      hairpin intermediate is formed at the coding ends early in the reaction. Here,
      inverted repeats at processed coding ends were present at approximately twice the
      number of junctions as P nucleotide additions. Terminal deoxynucleotidyl
      transferase (TdT) is required for the appearance of the inverted repeats at
      processed ends (but not full-length coding ends), yet statistical analysis shows
      that it is virtually impossible for the inverted repeats to be polymerized by
      TdT. Third, TdT additions are not random. It has long been noted that TdT has a G
      utilization preference. In addition to the G preference, we find that TdT adds
      strings of purines or strings of pyrimidines at a highly significant frequency.
      This tendency suggests that nucleotide-stacking interactions affect TdT
      polymerization. All three of these features place constraints on the extent of
      junctional diversity in human V(D)J recombination.

PMID- 8524304
TI  - Stimulation of proliferation of a human osteosarcoma cell line by exogenous
      acidic fibroblast growth factor requires both activation of receptor tyrosine
      kinase and growth factor internalization.
AB  - U2OS Dr1 cells, originating from a human osteosarcoma, are resistant to the
      intracellular action of diphtheria toxin but contain toxin receptors on their
      surfaces. These cells do not have detectable amounts of fibroblast growth factor
      receptors. When these cells were transfected with fibroblast growth factor
      receptor 4, the addition of acidic fibroblast growth factor to the medium induced
      tyrosine phosphorylation, DNA synthesis, and cell proliferation. A considerable
      fraction of the cell-associated growth factor was found in the nuclear fraction.
      When the growth factor was fused to the diphtheria toxin A fragment, it was still
      bound to the growth factor receptor and induced tyrosine phosphorylation but did
      not induce DNA synthesis or cell proliferation, nor was any fusion protein
      recovered in the nuclear fraction. On the other hand, when the fusion protein was
      associated with the diphtheria toxin B fragment to allow translocation to the
      cytosol by the toxin pathway, the fusion protein was targeted to the nucleus and
      stimulated both DNA synthesis and cell proliferation. In untransfected cells
      containing toxin receptors but not fibroblast growth factor receptors, the fusion
      protein was translocated to the cytosol and targeted to the nucleus, but in this
      case, it stimulated only DNA synthesis. These data indicate that the following
      two signals are required to stimulate cell proliferation in transfected U2OS Dr1
      cells: the tyrosine kinase signal from the activated fibroblast growth factor
      receptor and translocation of the growth factor into the cell.

PMID- 8524305
TI  - Unliganded thyroid hormone receptor alpha can target TATA-binding protein for
      transcriptional repression.
AB  - Unliganded human thyroid hormone receptor alpha (hTR alpha) can repress
      transcription by inhibiting the formation of a functional preinitiation complex
      (PIC) on promoters bearing thyroid hormone receptor (TR)-binding elements. Here
      we demonstrate that hTR alpha directly contacts the TATA-binding protein (TBP)
      and that preincubation of hTR alpha with TBP completely alleviates TR-mediated
      repression in vitro. Using stepwise preassembled PICs, we show that hTR alpha
      targets either the TBP/TFIIA or the TBP/TFIIA/TFIIB steps of PIC assembly for
      repression. We also show that the repression domain of hTR alpha maps to the C
      terminal ligand-binding region and that direct TR-TBP interactions can be
      inhibited by thyroid hormone. Together, these results suggest a model in which
      unliganded hTR alpha contacts promoter-bound TBP and interferes with later steps
      in the initiation of transcription.

PMID- 8524306
TI  - Function of Stat2 protein in transcriptional activation by alpha interferon.
AB  - Alpha interferon (IFN-alpha)-induced transcriptional activation requires the
      induction of a complex of DNA-binding proteins, including tyrosine-phosphorylated
      Stat1 and Stat2, and of p48, a protein which is not phosphorylated on tyrosine
      and which comes from a separate family of DNA-binding proteins. The isolation and
      characterization of U6A cells, which lack Stat2, have allowed the introduction of
      normal and mutant forms of Stat2 so that various functions of the Stat2 protein
      can be examined. As reported earlier, Stat1, which is the second target of
      tyrosine phosphorylation in IFN-alpha-treated cells, is not phosphorylated in the
      absence of Stat2. We show that all mutations that block Stat2 phosphorylation
      also block Stat1 phosphorylation. These include not only the mutations of Y-690
      and SH2 domain residues that are involved in tyrosine phosphorylation but also
      short deletions at the amino terminus of the protein. Two mutants of Stat2 that
      are not phosphorylated on tyrosine can act as dominant negative proteins in
      suppressing wild-type Stat2 phosphorylation, most likely by competition at the
      receptor-kinase interaction site(s). We also show that the COOH-terminal 50 amino
      acids are required for transcriptional activation in response to IFN-alpha.
      Mutants lacking these amino acids can be phosphorylated, form IFN-stimulated gene
      factor 3, and translocate to the nucleus but cannot stimulate IFN-alpha-dependent
      transcription. Seven acidic residues are present in the deleted COOH-terminal
      residues, but 24 acidic residues still remain in the 100 carboxy-terminal amino
      acids after deletion. Thus, transcriptional activation is unlikely to depend on
      acidic amino acids alone.

PMID- 8524307
TI  - An alternative, nonkinase product of the brain-specifically expressed
      Ca2+/calmodulin-dependent kinase II alpha isoform gene in skeletal muscle.
AB  - The gene for the alpha isoform of Ca2+/calmodulin-dependent kinase II (alpha
      CaMKII) codes for a multifunctional protein kinase that is found exclusively in
      the brain. Here we show that in skeletal muscle, an alternative nonkinase
      product, hereafter referred to as alpha KAP (alpha CaMKII association protein),
      is expressed from the same gene. alpha KAP consists of a C-terminal region that
      is identical to the association domain of alpha CaMKII, with the exception of 11
      amino acids inserted in the variable region. The N-terminal sequence of alpha KAP
      is highly hydrophobic and not present in any known CaMKII protein. The catalytic
      and regulatory domains of alpha CaMKII are missing in alpha KAP. Analysis of the
      exon-intron structure revealed that the alpha KAP transcript is derived from the
      alpha CaMKII gene by alternative promoter usage and RNA splicing. The
      transcriptional start site of alpha KAP mRNA is located within an intron of the
      alpha CaMKII gene. Therefore, the relationship between alpha KAP and alpha CaMKII
      is that of a gene within a gene. Immunostaining using anti-alpha KAP antibodies
      suggests that alpha KAP is associated with sarcomeres of skeletal muscle fibers.
      On the basis of its primary structure and specific location, the possible
      function of alpha KAP as an anchoring protein for CaMKII is discussed.

PMID- 8524308
TI  - Yeast nucleoporin mutants are defective in pre-tRNA splicing.
AB  - We have screened nucleoporin mutants for the inhibition of tRNA splicing, which
      has previously been proposed to be coupled to transport. Strains mutant for
      Nup49p or Nup116p, or genetically depleted of Nup145p, strongly accumulated
      unspliced pre-tRNAs. Splicing was inhibited for all 10 families of intron
      containing pre-tRNA, but no effects on 5' or 3' end processing were detected.
      Strains mutant for Nup133p or Nsp1p accumulated lower levels of several unspliced
      pre-tRNAs. In contrast, no accumulation of any pre-tRNA was observed in strains
      mutant for Nup1p, Nup85p, or Nup100p. Other RNA processing reactions tested, pre
      rRNA processing, pre-mRNA splicing, and small nucleolar and small nuclear RNA
      synthesis, were not clearly affected for any nucleoporin mutant. These data
      provide evidence for a coupling between pre-tRNA splicing and nuclear-cytoplasmic
      transport. Mutation of NUP49, NUP116, or NUP145 has previously been shown to lead
      to nuclear poly(A)+ RNA accumulation, indicating that these nucleoporins play
      roles in the transport of more than one class of RNA.

PMID- 8524309
TI  - Mapping of genomic DNA loop organization in a 500-kilobase region of the
      Drosophila X chromosome by the topoisomerase II-mediated DNA loop excision
      protocol.
AB  - The recently developed procedure of chromosomal DNA loop excision by
      topoisomerase II-mediated DNA cleavage at matrix attachment sites (S. V. Razin,
      R. Hancock, O. Iarovaia, O. Westergaard, I. Gromova, and G. P. Georgiev, Cold
      Spring Harbor Symp. Quant. Biol. 58:25-35, 1993; I. I. Gromova, B. Thompsen, and
      S. V. Razin, Proc. Natl. Acad. Sci. USA 92:102-106, 1995) has been employed for
      mapping the DNA loop anchorage sites in a 500-kb region of the Drosophila
      melanogaster X chromosome. Eleven anchorage sites delimiting 10 DNA loops ranging
      in size from 20 to 90 kb were found within this region. Ten of these 11 anchorage
      sites colocalize with previously mapped scaffold attachment regions. However, a
      number of other scaffold attachment regions are found to be located in loop DNA.

PMID- 8524310
TI  - A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient
      for Jak kinase activation and induction of proliferation in T cells.
AB  - The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits
      (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes.
      Intracellular signalling results from ligand-mediated heterodimerization of the
      cytoplasmic domains of the beta and gamma c chains. To identify the residues of
      gamma c critical to this process, mutations were introduced into the cytoplasmic
      domain, and the effects on signalling were analyzed in the IL-2-dependent T-cell
      line CTLL2 and T-helper clone D10, using chimeric IL-2R chains that bind and are
      activated by granulocyte-macrophage colony-stimulating factor. Whereas previous
      studies of fibroblasts and transformed T cells have suggested that signalling by
      gamma c requires both membrane-proximal and C-terminal subdomains, our results
      for IL-2-dependent T cells demonstrate that the membrane-proximal 52 amino acids
      are sufficient to mediate a normal proliferative response, including induction of
      the proto-oncogenes c-myc and c-fos. Although gamma c is phosphorylated on
      tyrosine upon receptor activation and could potentially interact with downstream
      molecules containing SH2 domains, cytoplasmic tyrosine residues were dispensable
      for mitogenic signalling. However, deletion of a membrane-proximal region
      conserved among other cytokine receptors (cytoplasmic residues 5 to 37) or an
      adjacent region unique to gamma c (residues 40 to 52) abrogated functional
      interaction of the receptor chain with the tyrosine kinase Jak3. This correlated
      with a loss of all signalling events analyzed, including phosphorylation of the
      IL-2R beta-associated kinase Jak1, expression of c-myc and c-fos, and induction
      of the proliferative response. Thus, it appears in T cells that Jak3 is a
      critical mediator of mitogenic signaling by the gamma c chain.

PMID- 8524311
TI  - Vitamin D interferes with transactivation of the growth hormone gene by thyroid
      hormone and retinoic acid.
AB  - The thyroid hormone, retinoic acid (RA), and vitamin D regulate gene expression
      by binding to similar receptors which act as ligand-inducible transcription
      factors. Incubation of pituitary GH4C1 cells with nanomolar concentrations of
      vitamin D markedly reduces the response of the rat growth hormone mRNA to thyroid
      hormone triiodothyronine (T3) and RA. The stimulation of growth hormone gene
      expression by both ligands is mediated by a common hormone response element
      (TREGH) present in the 5'-flanking region of the gene, and the inhibition caused
      by vitamin D is due to transcriptional interference of the vitamin D receptor on
      this DNA element. No inhibition of the basal promoter activity by the vitamin was
      observed. The response to T3 and RA of a heterologous promoter containing this
      element, the palindromic T3- and RA-responsive sequence TREPAL, or a direct
      repeat of the same motif is also inhibited by vitamin D. In contrast, vitamin D
      strongly induces the activity of constructs containing a vitamin D response
      element, and neither T3 nor RA reduces vitamin D-mediated transactivation.
      Transfection with an expression vector for the retinoid X receptor alpha (RXR
      alpha) increases transactivation by T3 and RA but does not abolish the inhibition
      caused by the vitamin. Gel retardation experiments show that the vitamin D
      receptor (VDR) as a heterodimer with RXR weakly binds to the T3- and RA
      responsive elements. Additionally, VDR displaces binding of T3 and RA receptors
      in a dose-dependent manner. Our data suggest the formation of TR-VDR and RAR-VDR
      heterodimers with RXR. The fact that the same response element mediates opposite
      effects of at least four different nuclear receptors provides a greater
      complexity and flexibility of the transcriptional responses to their ligands.

PMID- 8524312
TI  - Three classes of mutations in the A subunit of the CCAAT-binding factor CBF
      delineate functional domains involved in the three-step assembly of the CBF-DNA
      complex.
AB  - The mammalian CCAAT-binding factor CBF (also called NF-Y or CP1) consists of
      three subunits, CBF-A, CBF-B, and CBF-C, all of which are required for DNA
      binding and present in the CBF-DNA complex. In this study we first established
      the stoichiometries of the CBF subunits, both in the CBF molecule and in the CBF
      DNA complex, and showed that one molecule of each subunit is present in the
      complex. To begin to understand the interactions between the CBF subunits and
      DNA, we performed a mutational analysis of the CBF-A subunit. This analysis
      identified three classes of mutations in the segment of CBF-A that is conserved
      in Saccharomyces cerevisiae and mammals. Analysis of the first class of mutants
      revealed that a major part of the conserved segment was essential for
      interactions with CBF-C to form a heterodimeric CBF-A/CBF-C complex. The second
      class of mutants identified a segment of CBF-A that is necessary for interactions
      between the CBF-A/CBF-C heterodimer and CBF-B to form a CBF heterotrimer. The
      third class defined a domain of CBF-A involved in binding the CBF heterotrimer to
      DNA. The second and third classes of mutants acted as dominant negative mutants
      inhibiting the formation of a complex between the wild-type CBF subunits and DNA.
      The segment of CBF-A necessary for DNA binding showed sequence homology to a
      segment of CBF-C. Interestingly, these sequences in CBF-A and CBF-C were also
      homologous to the sequences in the histone-fold motifs of histones H2B and H2A,
      respectively, and to the archaebacterial histone-like protein HMf-2. We discuss
      the functional domains of CBF-A and the properties of CBF in light of these
      sequence homologies and propose that an ancient histone-like motif in two CBF
      subunits controls the formation of a heterodimer between these subunits and the
      assembly of a sequence-specific DNA-protein complex.

PMID- 8524313
TI  - The retrotransposon Tf1 assembles virus-like particles that contain excess Gag
      relative to integrase because of a regulated degradation process.
AB  - The retrotransposon Tf1, isolated from Schizosaccharomyces pombe, contains a
      single open reading frame with sequences encoding Gag, protease, reverse
      transcriptase, and integrase (IN). Tf1 has previously been shown to possess
      significant transposition activity. Although Tf1 proteins do assemble into virus
      like particles, the assembly does not require readthrough of a translational
      reading frame shift or stop codon, common mechanisms used by retroelements to
      express Gag in molar excess of the polymerase proteins. This study was designed
      to determine if Tf1 particles contain equal amounts of Gag and polymerase
      proteins or whether they contain the typical molar excess of Gag. After using two
      separate methods to calibrate the strength of our antibodies, we found that both
      S. pombe extracts and partially purified Tf1 particles contained a 26-fold molar
      excess of Gag relative to IN. Knowing that Gag and IN are derived from the same
      Tf1 primary translation product, we concluded that the excess Gag most likely
      resulted from specific degradation of IN. We obtained evidence of regulated IN
      degradation in comparisons of Tf1 protein extracted from log-phase cells and that
      extracted from stationary-phase cells. The log-phase cells contained equal molar
      amounts of Gag and IN, whereas cells approaching stationary phase rapidly
      degraded IN, leaving an excess of Gag. Analysis of the reverse transcripts
      indicated that the bulk of reverse transcription occurred within the particles
      that possess a molar excess of Gag.

PMID- 8524314
TI  - Isolation and analysis of the yeast TEA1 gene, which encodes a zinc cluster Ty
      enhancer-binding protein.
AB  - A genetic screen for mutants that affect the activity of internal regulatory
      sequences of Ty retrotransposons led to the identification of a new gene encoding
      a DNA-binding protein that interacts with the downstream enhancer-like region of
      Ty1 elements. The TEA1 (Ty enhancer activator) gene sequence predicts a protein
      of 86.9 kDa whose N terminus contains a zinc cluster and dimerization motif
      typical of the Gal4-type family of DNA-binding proteins. The C terminus encodes
      an acidic domain with a net negative charge of -10 and the ability to mediate
      transcriptional activation. Like other zinc cluster proteins, purified Tea1 was
      found to bind to a partially palindromic CGGNxCCG repeat motif located in the Ty1
      enhancer region. The Ty1 Tea1 binding site has a spacing of 10 and is located
      near binding sites for the DNA-binding proteins Rap1 and Mcm1. Analysis of the
      phenotype of tea1 deletion mutants confirmed that the TEA1 gene is required for
      activation from the internal Ty1 enhancer characterized in this study and makes a
      modest contribution to normal Ty1 levels in the cell. Hence, Tea1, like Rap1, is
      a member of a small family of downstream activators in Saccharomyces cerevisiae.
      Further analysis of the Tea1 protein and its interactions may provide insight
      into the mechanism of downstream activation in yeast cells.

PMID- 8524315
TI  - The interferon-inducible p202 protein as a modulator of transcription: inhibition
      of NF-kappa B, c-Fos, and c-Jun activities.
AB  - The antimicrobial, immunomodulatory, and cell growth-regulatory activities of the
      interferons are mediated by interferon-inducible proteins. One of these is p202,
      a nuclear protein that is encoded by the Ifi 202 gene from the interferon
      activatable gene 200 cluster. Overexpression of p202 in transfected cells slows
      down cell proliferation. As shown earlier, p202 binds to the hypophosphorylated
      form of the retinoblastoma susceptibility protein. Here we report that p202
      inhibits the activities of the NF-kappa B and the AP-1 enhancers both in
      transiently transfected cells and in transfected stable cell lines overexpressing
      p202. Furthermore, p202 binds the NF-kappa B p50 and p65 and the AP-1 c-Fos and c
      Jun transcription factors in vitro and in vivo. NF-kappa B, c-Fos, and c-Jun
      participate in the transcription of various cellular and viral genes, and thus
      p202 can modulate the expression of these genes in response to interferons.

PMID- 8524316
TI  - Roles of JAKs in activation of STATs and stimulation of c-fos gene expression by
      epidermal growth factor.
AB  - The tyrosine kinase JAK1 and the transcription factors STAT1 and STAT3 are
      phosphorylated in response to epidermal growth factor (EGF) and other growth
      factors. We have used EGF receptor-transfected cell lines defective in individual
      JAKs to assess the roles of these kinases in STAT activation and signal
      transduction in response to EGF. Although JAK1 is phosphorylated in response to
      EGF, it is not required for STAT activation or for induction of the c-fos gene.
      STAT activation in JAK2- and TYK2-defective cells is also normal, and the
      tyrosine phosphorylation of these two kinases does not increase upon EGF
      stimulation in wild-type or JAK1-negative cells. In cells transfected with a
      kinase-negative mutant EGF receptor, there is no STAT activation in response to
      EGF and c-fos is not induced, showing that the kinase activity of the receptor is
      required, directly or indirectly, for these two responses. The data do not
      support a role for any of the three JAK family members tested in STAT activation
      and are consistent with a JAK-independent pathway in which the intrinsic kinase
      domain of the EGF receptor is crucial. Furthermore, data from transient
      transfection experiments in HeLa cells, using c-fos promoters lacking the STAT
      regulatory element c-sis-inducible element, indicate that this element may play
      only a minor role in the induction of c-fos by EGF in these cells.

PMID- 8524317
TI  - p95vav associates with the nuclear protein Ku-70.
AB  - The proto-oncogene vav is expressed solely in hematopoietic cells and plays an
      important role in cell signaling, although little is known about the proteins
      involved in these pathways. To gain further information, the Src homology 2 (SH2)
      and 3 (SH3) domains of Vav were used to screen a lymphoid cell cDNA library by
      the yeast two-hybrid system. Among the positive clones, we detected a nuclear
      protein, Ku-70, which is the DNA-binding element of the DNA-dependent protein
      kinase. In Jurkat and UT7 cells, Vav is partially localized in the nuclei, as
      judged from immunofluorescence and confocal microscopy studies. By using
      glutathione S-transferase fusion proteins derived from Ku-70 and
      coimmunoprecipitation experiments with lysates prepared from human thymocytes and
      Jurkat and UT7 cells, we show that Vav associates with Ku-70. The interaction of
      Vav with Ku-70 requires only the 150-residue carboxy-terminal portion of Ku-70,
      which binds to the 25 carboxy-terminal residues of the carboxy SH3 domain of Vav.
      A proline-to-leucine mutation in the carboxy SH3 of Vav that blocks interaction
      with proline-rich sequences does not modify the binding of Ku-70, which lacks
      this motif. Therefore, the interaction of Vav with Ku-70 may be a novel form of
      protein-protein interaction. The potential role of Vav/Ku-70 complexes is
      discussed.

PMID- 8524318
TI  - Splicing signals are required for S-phase regulation of the mouse thymidylate
      synthase gene.
AB  - The thymidylate synthase (TS) gene is expressed at a much higher level in cells
      undergoing DNA replication than in nondividing cells. In growth-stimulated
      mammalian cells, TS mRNA content increases 10 to 20-fold as cells progress from
      G1 through S phase. However, the rate of transcription of the TS gene does not
      increase during this interval, indicating that the gene is regulated at the
      posttranscriptional level. We have shown that both the promoter of the mouse TS
      gene and TS introns are necessary (although neither is sufficient) for S-phase
      specific regulation of TS mRNA content. In the present study, we examined in more
      detail the role of introns in regulating TS mRNA levels in growth-stimulated
      cells. TS minigenes that contain normal or modified introns were stably
      transfected into mouse 3T6 fibroblasts, and the regulation of the minigenes was
      compared with that of the endogenous TS gene. TS minigenes that contain TS intron
      1 or 2 maintain S-phase regulation. Deletion of most of the interior of the
      introns had only minor effects on regulation. However, when splicing of the
      intron was inhibited by alteration of the splice donor and acceptor sites, the
      minigene was expressed at a constant level following growth stimulation.
      Minigenes consisting of the TS promoter linked to either a luciferase or a human
      beta-globin indicator gene were growth regulated when spliceable introns were
      included in the minigenes. However, when the introns were eliminated, the
      minigenes were expressed at a constant level. These observations indicate that
      the splicing reaction itself, rather than a control sequence within the intron,
      is important for growth-regulated expression of the TS gene. Possible mechanisms
      to account for the dual requirement for the TS promoter and intron splicing for
      proper regulation of the TS gene are discussed.

PMID- 8524319
TI  - Tissue- and stage-specific activation of an endogenous provirus after
      transcription through its integration site in the opposite orientation.
AB  - Endogenous proviruses of the Moloney murine leukemia retrovirus (Mo-MuLV) are
      transcriptionally blocked in early embryos and in general remain silent even when
      the tissues have become permissive to the expression of newly integrated copies.
      Eventually, activation in presumably very few cells initiates rapid
      superinfection leading to viremia and leukemia, but the processes leading to
      provirus activation are unknown. Differences in the onset and development of
      viremia between several mouse strains carrying an endogenous Mo-MuLV (Mov lines)
      are attributed to a chromosomal position effect, but neither cell type nor stage
      of provirus activation is known for any strain. We have now monitored the
      appearance of viral transcripts and particles in the Mov13 strain, which carries
      the Mo-MuLV provirus in inverted orientation in the first intron of a collagen
      gene (Col1a1) with well-characterized transcriptional activity. We report
      obligatory tissue- and stage-specific virus activation in osteoblasts and
      odontoblasts. The significance of this activation pattern is indicated by the
      fact that of the great variety of cells expressing the wild-type collagen gene,
      only these two cell types can also transcribe the mutant allele including its
      viral insert. We propose that this transcription of the proviral genome, albeit
      in the opposite direction, leads to the activation of the viral promoter.

PMID- 8524320
TI  - Activation of transcription by PU.1 requires both acidic and glutamine domains.
AB  - The B-lymphocyte- and macrophage-specific transcription factor PU.1 is a member
      of the ets family of proteins. To understand how PU.1 functions as a
      transcription factor, we initiated a series of experiments to define its
      activation domain. Using deletion analysis, we showed that the activation domain
      of PU.1 is located in the amino-terminal half of the protein. Within this region,
      we identified three acidic subdomains and one glutamine-rich subdomain. The
      deletion of any of these subdomains resulted in a significant loss in the ability
      of PU.1 to transactivate in cotransfection studies. Amino acid substitution
      analysis showed that the activation of transcription by PU.1 requires acidic
      residues between amino acids 7 and 74 and a group of glutamine residues between
      amino acids 75 and 84. These data show that PU.1 contains two types of known
      activation domains and that both are required for maximal transactivation.

PMID- 8524321
TI  - Evidence for the involvement of a nuclear NF-kappa B inhibitor in global down
      regulation of the major histocompatibility complex class I enhancer in adenovirus
      type 12-transformed cells.
AB  - Diminished expression of major histocompatibility complex class I antigens on the
      surface of adenovirus type 12 (Ad12)-transformed cells contributes to their high
      tumorigenic potential by enabling them to escape immune recognition by cytotoxic
      T lymphocytes. This low class I antigen expression is due to a block in class I
      transcription, which is mediated by Ad12 E1A. Genetic analysis has shown that the
      class I enhancer is the target for transcriptional down-regulation. In this
      study, we show that the ability of the R1 element of the class I enhancer to
      stimulate transcription is greatly reduced in Ad12-transformed cells. The loss of
      functional activity by the R1 element was attributed to loss of binding by the NF
      kappa B p50-p65 heterodimer. NF-kappa B binding appears to be blocked within the
      nucleus rather than at the level of nuclear translocation. Significantly, NF
      kappa B binding activity could be recovered from the nuclear extracts of Ad12
      transformed cells following detergent treatment, suggesting that the block is
      mediated through a nuclear inhibitor present in the Ad12-transformed cells. These
      results, taken together with the fact that the R2 element of the class I enhancer
      exhibits strong binding to the transcriptional repressor COUP-TF, suggest that
      the class I enhancer is globally down-regulated in Ad12-transformed cells.

PMID- 8524322
TI  - Constitutive activation of S6 kinase by deletion of amino-terminal autoinhibitory
      and rapamycin sensitivity domains.
AB  - The mitogen response of p70/p85 S6 kinase (S6K) parallels that of mitogen
      activated protein kinases (MAPK). However, S6K lies on a discrete signaling
      pathway from MAPK, since the immunosuppressant drug rapamycin inactivates S6K
      without affecting the MAPK cascade. Phosphatidylinositol 3-kinase operates
      upstream of S6K, but the intermediate effectors in this signaling pathway are
      unknown. We have identified an autoinhibitory domain in S6K that overrides the
      requirement of the amino terminus for the activation of S6K. The region between
      codons 58 and 77 is highly inhibitory, and its deletion results in constitutive
      kinase activation. Additionally, deletion of the first 77 codons confers mitogen
      independence and insensitivity to rapamycin. Rat1 cells expressing delta N77 S6K
      exhibit a distinctly abnormal morphology. This constitutively active mutant will
      provide a useful means of studying the effects of expressing unregulated S6K in
      cells. Subdeletion analysis of the amino terminus has defined two discrete
      domains in the N terminus of S6K--a domain between codons 1 and 58 is essential
      for the mitogen activation of S6K and confers rapamycin sensitivity; a second
      domain between codons 58 and 77 confers autoinhibition. We propose a model for
      the activation of S6 kinase in which mitogen-stimulated cellular factors interact
      with the amino terminus to negate the effects of the autoinhibitory domain.

PMID- 8524323
TI  - DNA methylation specifies chromosomal localization of MeCP2.
AB  - MeCP2 is a chromosomal protein that is concentrated in the centromeric
      heterochromatin of mouse cells. In vitro, the protein binds preferentially to DNA
      containing a single symmetrically methylated CpG. To find out whether the
      heterochromatic localization of MeCP2 depended on DNA methylation, we transiently
      expressed MeCP2-LacZ fusion proteins in cultured cells. Intact protein was
      targeted to heterochromatin in wild-type cells but was inefficiently localized in
      mutant cells with low levels of genomic DNA methylation. Deletions within MeCP2
      showed that localization to heterochromatin required the 85-amino-acid methyl-CpG
      binding domain but not the remainder of the protein. Thus MeCP2 is a methyl-CpG
      binding protein in vivo and is likely to be a major mediator of downstream
      consequences of DNA methylation.

PMID- 8524324
TI  - Splicing removes the Caenorhabditis elegans transposon Tc1 from most mutant pre
      mRNAs.
AB  - The transposable element Tc1 is responsible for most spontaneous mutations that
      occur in many Caenorhabditis elegans strains. We analyzed the abundance and
      sequence of mRNAs expressed from five different Tc1 insertions within either hlh
      1 (a MyoD homolog) or unc-54 (a myosin heavy chain gene). Each of the mutants
      expresses substantial quantities of mature mRNA in which most or all of Tc1 has
      been removed by splicing. Such mRNAs contain small insertions of Tc1 sequences
      and/or deletions of target gene sequences at the resulting spliced junctions.
      Most of these mutant mRNAs do not contain premature stop codons, and many are
      translated in frame to produce proteins that are functional in vivo. The number
      and variety of splice sites used to remove Tc1 from these mutant pre-mRNAs are
      remarkable. Two-thirds of the Tc1-containing introns removed from hlh-1 and unc
      54 lack either the 5'-GU or AG-3' dinucleotides typically found at the termini of
      eukaryotic introns. We conclude that splicing to remove Tc1 from mutant pre-mRNAs
      allows many Tc1 insertions to be phenotypically silent. Such mRNA processing may
      help Tc1 escape negative selection.

PMID- 8524325
TI  - Dioxin-induced CYP1A1 transcription in vivo: the aromatic hydrocarbon receptor
      mediates transactivation, enhancer-promoter communication, and changes in
      chromatin structure.
AB  - We have analyzed the dioxin-inducible transcriptional control mechanism for the
      mouse CYP1A1 gene in its native chromosomal context. Our genetic and biochemical
      studies indicate that a C-terminal segment of the aromatic hydrocarbon receptor
      (AhR) contains latent transactivation capability and communicates the induction
      signal from enhancer to promoter. Thus, transactivation and enhancer-promoter
      communication may be congruent functions of AhR. Both functions require
      heterodimerization between AhR and the AhR nuclear translocator (Arnt). Our
      findings also indicate that heterodimerization activates AhR's latent
      transactivation function and silences that of Arnt. Furthermore, removal of
      Arnt's transactivation domain does not affect dioxin-induced CYP1A1 transcription
      in vivo. In addition, our studies demonstrate that dioxin-induced changes in
      chromatin structure occur by different mechanisms at the CYP1A1 enhancer and
      promoter and that events at an enhancer can be experimentally dissociated from
      events at the cognate promoter during mechanistic analyses of mammalian
      transcription in vivo.

PMID- 8524326
TI  - Quantitative discrimination of MEF2 sites.
AB  - Myocyte-specific enhancer factor 2 (MEF2) is a family of closely related
      transcription factors that play a key role in the differentiation of muscle
      tissues and are important in the muscle-specific expression of a number of genes.
      Given the centrality of MEF2 in muscle differentiation, regulatory regions newly
      determined to be muscle specific are often studied for potential MEF2 binding
      sites. Possible sites are often located by comparison to a homologous gene or by
      matching to the consensus MEF2 sequence. Enough data have accumulated that a
      richer description of the MEF2 binding site, a position weight matrix, can be
      reliably constructed and its usefulness can be assessed. It was shown that scores
      from such a matrix approximate MEF2 binding energy and enable recognition of
      naturally occurring MEF2 sites with high sensitivity and specificity. Regulation
      of genes via MEF2-like sites is complicated by the fact that a number of
      transcription factors are involved. Not only is MEF2 itself a family of proteins,
      but several other, nonhomologous, transcription factors overlap MEF2 in DNA
      binding specificity. Thus, more quantitative methods for recognizing potential
      sites may help with the lengthy process of disentangling the complex regulatory
      circuits of muscle-specific expression.

PMID- 8524327
TI  - Glucose-induced sequential processing of a glycosyl-phosphatidylinositol-anchored
      ectoprotein in Saccharomyces cerevisiae.
AB  - Transfer of spheroplasts from the yeast Saccharomyces cerevisiae to glucose leads
      to the activation of an endogenous (glycosyl)-phosphatidylinositol-specific
      phospholipase C ([G]PI-PLC), which cleaves the anchor of at least one glycosyl
      phosphatidylinositol (GPI)-anchored protein, the cyclic AMP (cAMP)-binding
      ectoprotein Gce1p (G. Muller and W. Bandlow, J. Cell Biol. 122:325-336, 1993).
      Analyses of the turnover of two constituents of the anchor, myo-inositol and
      ethanolamine, relative to the protein label as well as separation of the two
      differently processed versions of Gce1p by isoelectric focusing in spheroplasts
      demonstrate the glucose-induced conversion of amphiphilic Gce1p first into a
      lipolytically cleaved hydrophilic intermediate, which is then processed into
      another hydrophilic version lacking both myo-inositol and ethanolamine. When
      incubated with unlabeled spheroplasts, the lipolytically cleaved intermediate
      prepared in vitro is converted into the version lacking all anchor constituents,
      whereby the anchor glycan is apparently removed as a whole. The secondary
      cleavage ensues independently of the carbon source, attributing the key role in
      glucose-induced anchor processing to the endogenous (G)PI-PLC. The secondary
      processing of the lipolytically cleaved intermediate of Gce1p at the plasma
      membrane is correlated with the emergence of a covalently linked high-molecular
      weight form of a cAMP-binding protein at the cell wall. This protein lacks anchor
      components, and its protein moiety appears to be identical with double-processed
      Gce1p detectable at the plasma membrane in spheroplasts. The data suggest that
      glucose-induced double processing of GPI anchors represents part of a mechanism
      of regulated cell wall expression of proteins in yeast cells.

PMID- 8524328
TI  - The product of the cbl oncogene forms stable complexes in vivo with endogenous
      Crk in a tyrosine phosphorylation-dependent manner.
AB  - The cellular homologs of the v-Crk oncogene product are composed exclusively of
      Src homology region 2 (SH2) and SH3 domains. v-Crk overexpression in fibroblasts
      causes cell transformation and elevated tyrosine phosphorylation of specific
      cellular proteins. Among these proteins is a 130-kDa protein, identified as
      p130cas, that forms a stable complex in vivo with v-Crk. We have explored the
      role of endogenous Crk proteins in Bcr-Abl-transformed cells. In the K562 human
      chronic myelogenous leukemia cell line, p130cas is not tyrosine phosphorylated or
      bound to Crk. Instead, Crk proteins predominantly associate with the tyrosine
      phosphorylated proto-oncogene product of Cbl. In vitro analysis showed that this
      interaction is mediated by the SH2 domain of Crk and can be inhibited with a
      phosphopeptide containing the Crk-SH2 binding motif. In NIH 3T3 cells transformed
      by Bcr-Abl, c-Cbl becomes strongly tyrosine phosphorylated and associates with c
      Crk. The complex between c-Crk and c-Cbl is also seen upon T-cell receptor cross
      linking or with the transforming, tyrosine-phosphorylated c-Cbl. These results
      indicate that Crk binds to c-Cbl in a tyrosine phosphorylation-dependent manner,
      suggesting a physiological role for the Crk-c-Cbl complex in Bcr-Abl tyrosine
      phosphorylation-mediated transformation.

PMID- 8524329
TI  - Effects of reverse transcriptase inhibitors on telomere length and telomerase
      activity in two immortalized human cell lines.
AB  - The ribonucleoprotein telomerase, a specialized cellular reverse transcriptase,
      synthesizes one strand of the telomeric DNA of eukaryotes. We analyzed telomere
      maintenance in two immortalized human cell lines: the B-cell line JY616 and the T
      cell line Jurkat E6-1, and determined whether known inhibitors of retroviral
      reverse transcriptases could perturb telomere lengths and growth rates of these
      cells in culture. Dideoxyguanosine (ddG) caused reproducible, progressive
      telomere shortening over several weeks of passaging, after which the telomeres
      stabilized and remained short. However, the prolonged passaging in ddG caused no
      observable effects on cell population doubling rates or morphology.
      Azidothymidine (AZT) caused progressive telomere shortening in some but not all T
      and B-cell cultures. Telomerase activity was present in both cell lines and was
      inhibited in vitro by ddGTP and AZT triphosphate. Prolonged passaging in
      arabinofuranyl-guanosine, dideoxyinosine (ddI), dideoxyadenosine (ddA),
      didehydrothymidine (d4T), or phosphonoformic acid (foscarnet) did not cause
      reproducible telomere shortening or decreased cell growth rates or viabilities.
      Combining AZT, foscarnet, and/or arabinofuranyl-guanosine with ddG did not
      significantly augment the effects of ddG alone. Strikingly, with or without
      inhibitors, telomere lengths were often highly unstable in both cell lines and
      varied between parallel cell cultures. We propose that telomere lengths in these
      T- and B-cell lines are determined by both telomerase and telomerase-independent
      mechanisms.

PMID- 8524330
TI  - Specific RNA residue interactions required for enzymatic functions of Tetrahymena
      telomerase.
AB  - The ribonucleoprotein enzyme telomerase is a specialized reverse transcriptase
      that synthesizes telomeric DNA by copying a template sequence within the
      telomerase RNA. Here we analyze the actions of telomerase from Tetrahymena
      thermophila assembled in vivo with mutated or wild-type telomerase RNA to define
      further the roles of particular telomerase RNA residues involved in essential
      enzymatic functions: templating, substrate alignment, and promotion of
      polymerization. Position 49 of the telomerase RNA defined the 3' templating
      residue boundary, demonstrating that seven positions, residues 43 to 49, are
      capable of acting as templating residues. We demonstrate directly that
      positioning of the primer substrate involves Watson-Crick base pairing between
      the primer with telomerase RNA residues. Unexpectedly, formation of a Watson
      Crick base pair specifically between the primer DNA and telomerase RNA residue 50
      is critical in promoting primer elongation. In contrast, mutant telomerase with
      the cytosine at position 49 mutated to a G exhibited efficient 3' mispair
      extension. This work provides new evidence for specific primer-telomerase
      interactions, as well as base-specific interactions involving the telomerase RNA,
      playing roles in essential active-site functions of telomerase.

PMID- 8524331
TI  - Fast-muscle-specific DNA-protein interactions occurring in vivo at the human
      aldolase A M promoter are necessary for correct promoter activity in transgenic
      mice.
AB  - The human aldolase A tissue-specific M promoter (pM) has served as a model system
      for identifying pathways that lead to fast-muscle-specialized expression. The
      current study has delimited the sequences necessary and sufficient for fast
      muscle-specific expression in transgenic mice to a short 209-bp fragment
      extending from bp -164 to +45 relative to the pM transcription start site.
      Genomic footprinting methods showed that in this proximal region, the same
      elements that bind muscle nuclear proteins in vitro are involved in DNA-protein
      interactions in intact muscle nuclei of transgenic mice. Furthermore, these
      experiments provided the first evidence that different DNA-binding activities
      exist between slow and fast muscles in vivo. Fast-muscle-specific interactions
      occur at an element named M1 and at a muscle-specific DNase I-hypersensitive site
      that was previously detected by in vitro methods. The formation of the muscle
      specific DNase I-hypersensitive site reflects binding of proteins to a close
      element, named M2, which contains a binding site for nuclear factors of the NF1
      family. Mutational analysis performed with transgenic mice confirmed the
      importance of the M1 element for high-level fast-muscle-specific pM activity and
      suggested that the M2/NF1 element is differently required for correct pM
      expression in distinct fast muscles. In addition, two other protein binding
      sites, the MEF3 motif and the USF site, seem to act as stage-specific activators
      and/or as participants in the establishment of an active chromatin configuration
      at pM.

PMID- 8524332
TI  - Stockpiling of Cdc25 during a DNA replication checkpoint arrest in
      Schizosaccharomyces pombe.
AB  - The DNA replication checkpoint couples the onset of mitosis with the completion
      of S phase. It is clear that in the fission yeast Schizosaccharomyces pombe,
      operation of this checkpoint requires maintenance of the inhibitory tyrosyl
      phosphorylation of Cdc2. Cdc25 phosphatase induces mitosis by dephosphorylating
      tyrosine 15 of Cdc2. In this report, Cdc25 is shown to accumulate to a very high
      level in cells arrested in S. This shows that mechanisms which modulate the
      abundance of Cdc25 are unconnected to the DNA replication checkpoint. Using a
      Cdc2/cyclin B activation assay, we found that Cdc25 activity increased
      approximately 10-fold during transit through M phase. Cdc25 was activated by
      phosphorylations that were dependent on Cdc2 activity in vivo. Cdc25 activation
      was suppressed in cells arrested in G1 and S. However, Cdc25 was more highly
      modified and appeared to be somewhat more active in S than in G1. This finding
      might be connected to the fact that progression from G1 to S increases the
      likelihood that constitutive Cdc25 overproduction will cause inappropriate
      mitosis.

PMID- 8524334
TI  - Mutagenicity of tetranitroazoxytoluenes: a preliminary screening in Salmonella
      typhimurium strains TA100 and TA100NR.
AB  - Tetranitroazoxytoluenes are polynitroaromatic compounds that can be produced
      during the microbial reduction of the explosive, 2,4,6-trinitrotoluene (TNT). The
      three major tetranitroazoxytoluenes were synthesized and tested in Salmonella
      typhimurium strains TA100 and TA100NR. All compounds were mutagenic in TA100 but
      not in TA100NR, indicating the need for nitroreductase activity to induce
      mutagenicity. The most active chemical was 4,4',6,6'-tetranitro-2,2'-azoxytoluene
      (2735 rev/mumol) followed by 2',4,6,6'-tetranitro-2',4-azoxytoluene (929
      rev/mumol) and 2,2'-6,6'-tetranitro-4,4'-azoxytoluene (320 rev/mumol). These
      chemicals were more active than the aminodinitrotoluenes (298 rev/mumol for 2
      amino-4,6-dinitrotoluene and 115 rev/mumol for 4-amino-2,6-dinitrotoluene) and
      only 4,4',6,6'-tetranitro-2,2'-azoxytoluene was more active than the parent
      compound, TNT (1022 rev/mumol).

PMID- 8524333
TI  - Species-specific replication of simian virus 40 DNA in vitro requires the p180
      subunit of human DNA polymerase alpha-primase.
AB  - Human cell extracts efficiently support replication of simian virus 40 (SV40) DNA
      in vitro, while mouse cell extracts do not. Since human DNA polymerase alpha
      primase is the major species-specific factor, we set out to determine the
      subunit(s) of DNA polymerase alpha-primase required for this species specificity.
      Recombinant human, mouse, and hybrid human-mouse DNA polymerase alpha-primase
      complexes were expressed with baculovirus vectors and purified. All of the
      recombinant DNA polymerase alpha-primases showed enzymatic activity and
      efficiently synthesized the complementary strand on an M13 single-stranded DNA
      template. The human DNA polymerase alpha-primase (four subunits [HHHH]) and the
      hybrid DNA polymerase alpha-primase HHMM (two human subunits and two mouse
      subunits), containing human p180 and p68 and mouse primase, initiated SV40 DNA
      replication in a purified system. The human and the HHMM complex efficiently
      replicated SV40 DNA in mouse extracts from which DNA polymerase alpha-primase was
      deleted, while MMMM and the MMHH complex did not. To determine whether the human
      p180 or p68 subunit was required for SV40 DNA replication, hybrid complexes
      containing only one human subunit, p180 or p68, together with three mouse
      subunits (HMMM and MHMM) or three human subunits and one mouse subunit (MHHH and
      HMHH) were tested for SV40 DNA replication activity. The hybrid complexes HMMM
      and HMHH synthesized oligoribonucleotides in the SV40 initiation assay with
      purified proteins and replicated SV40 DNA in depleted mouse extracts. In
      contrast, the hybrid complexes containing mouse p180 were inactive in both
      assays. We conclude that the human p180 subunit determines host-specific
      replication of SV40 DNA in vitro.

PMID- 8524335
TI  - Assessment of smoking-induced DNA damage in lymphocytes of smoking mothers of
      newborn infants using the alkaline single-cell gel electrophoresis technique.
AB  - The single-cell gel electrophoretic (SCGE) technique for detecting the presence
      of DNA strand breaks and alkali-labile damage in individual cells was used to
      examine the effect on newborn infants of maternal exposure to cigarette smoke.
      The levels of DNA damage in the lymphocytes of 21 newborns of mothers with
      different smoking habits were compared to those in 10 newborn infants whose
      mothers had never smoked and 8 newborns whose mothers were passively exposed for
      at least 40 h per week in the workplace and home. DNA damage was undetected in
      lymphocytes of newborns of passively exposed mothers or newborns with mothers of
      low smoking habit by conditions allowing 40 min DNA unwinding and 40 min
      electrophoresis. Presumably longer times were needed for lower levels of damage
      to be detected by SCGE. The mean length of DNA migration in lymphocytes between
      the newborns of smoking mothers did not show any significance but the percentage
      of damaged cells increased with the frequency of smoking when assessed by non
      parametric Mann-Whitney U test. The results of SCGE were compared with our
      results published in the same individuals of sister-chromatid exchange (SCE)
      frequency. The results show similar trends with mean measures of DNA damage
      increasing with frequency and long history of maternal smoking. These
      observations encourage the application of SCGE as a sensitive and useful
      technique for quantitating DNA damage in individual cells.

PMID- 8524336
TI  - Mutagenic activation of aromatic amines by a human hepatoma cell (Hep G2)
      supernatant tested by means of Salmonella typhimurium strains with different
      acetyltransferase activities.
AB  - The study was carried out to characterize hepatoma cells (Hep G2) as activation
      system relevant to man and to investigate which are the tester strains most
      suitable for the mutagenic assay of aromatic amines. A supernatant prepared from
      the human hepatoma cell line Hep G2 was used to activate benzidine, 2
      aminofluorene (2-AF) and 2-acetylaminofluorene (2-AAF) in the Salmonella
      typhimurium reversion assay. Activation by Hep G2 supernatant was studied with
      increasing concentrations of the three compounds, in tester strains TA98, YG1024,
      DJ400 and DJ460. Benz[alpha]anthracene (BA) pretreatment of cells increases the
      mutagenicity of benzidine in strains YG1024, DJ460 and DJ400. Activation of 2-AAF
      and 2-AF was observed in strains YG1024, DJ400 and, at the highest tested dose,
      in DJ460. These results were compared with those obtained with S9 from control
      and Aroclor 1254 (Aro)-pretreated rat liver. With strain TA98 comparable
      responses were obtained except for 2-AF which was better activated using rat
      liver S9. The use of strain YG1024 greatly increases the sensitivity of the
      response. Strain DJ460 makes it possible to detect activation of 2-AF and 2-AAF
      by Aro-induced rat liver. These results indicate that Hep G2 supernatant is a
      useful metabolic activation system of human origin that can be used to replace
      rat liver S9. An appropriate choice of the Salmonella strain not only can
      increase the sensitivity of the response, but may also help to overcome certain
      metabolic shortcomings of the Hep G2 cell line and rat liver S9.

PMID- 8524337
TI  - The micronucleus assay using peripheral blood reticulocytes from X-ray-exposed
      mice.
AB  - A new 'fluorescence' variant of the micronucleus assay using supravital staining
      of peripheral blood reticulocytes with an acridine orange coated slide was
      recently developed. In this study the application of this method to detect a
      mutagenic response to low-dose exposure of X-irradiation is reported. The mice
      were exposed to a single dose of 2.5, 5, 10, 15, 25, and 50 cGy. The induction of
      micronuclei in peripheral blood reticulocytes was recorded with sampling times of
      0, 24, 48, 72, and 96 h after exposure without killing of mice. Dose-dependent
      effects were observed at sampling times of 24-72 h reaching maximum levels at 48
      h after X-ray exposure. A highly significant (p < 0.01) increase of the
      micronucleated reticulocytes was found for doses of 10, 15, 25, and 50 cGy.
      Neither the dose of 2.5 nor 5 cGy induced the significant increase in the
      incidence of micronucleated reticulocytes compared with the respective control
      group.

PMID- 8524338
TI  - Genotoxicity of potential metabolites of nitroscanate--an antischistosomal drug.
AB  - The potential metabolites of nitroscanate(4-isothiocyanato-4'-nitrodiphenyl
      ether) such as 4-amino-4'-nitrodiphenyl ether (ANDE), 4-acetamido-4'
      nitrodiphenyl ether (AcNDE), 4-acetamido-4'-nitrosodiphenyl ether (4-N = 0), 4
      acetamido-4'-hydroxylaminodiphenyl ether (4-NHOH), 4-acetamido-4'
      acetohydroxamicdiphenyl ether [4-N(OH)Ac], 4-acetamido-4'-formohydroxamicdiphenyl
      ether [4-N(OH)CHO] and 4-acetamido-4'-acetylaceto-hydroxamicdiphenyl ether [4
      N(OAc)Ac] were synthesized and investigated in the standard Salmonella
      mutagenicity test using TA98, TA98NR, TA98/1,8-DNP6, TA100 and TA100NR as
      indicator strains, in the presence and absence of hepatic S9. The relative order
      of activity among nitro and its reduction products, 4-N = 0 and 4-NHOH in TA98
      and TA100 was 4-N = 0 > 4-NHOH > AcNDE. In nitroreductase deficient strain
      TA98NR, AcNDE was inactive, but expressed a slight activity in TA100NR while 4-N
      = 0 and 4-NHOH showed a large increase in specific activity in both the strains.
      In O-acetyltransferase deficient strain TA98/1,8-DNP6, AcNDE was inactive, while
      4-N = O and 4-NHOH showed a sharp fall in activity. The hydroxylamine derived
      products with an activity order 4-N(OAc)Ac > 4-N(OH)CHO > 4-N(OH)Ac in both TA98
      and TA100, showed 3-6 times increase in the specific activity for the latter two
      compounds in the presence of S9 mix, which was inhibited in the presence of
      paraoxan, indicating N-deacylation as an important metabolic activation pathway.
      Except the 4-NO in TA100, the observed mutagenicity of nitroscante (NSC) was
      higher than those of potential metabolites and the nor-isothiocyanato derivative
      4'-nitrodiphenyl ether, thereby showing that -NCS function has a potentiating
      effect on the mutagenicity of this drug.

PMID- 8524339
TI  - Follow up study of chromosome aberrations in lymphocytes in hospital workers
      occupationally exposed to low levels of ionizing radiation.
AB  - In the present study we analyzed and followed up on the cytogenetic effects of
      low levels of ionizing X-radiation on hospital workers at 72 h cultures. Samples
      of peripheral blood were collected from 10 hospital workers exposed to 1.84
      mSv/year, and from 10 non exposed individuals, who were screened simultaneously
      and used as controls. The chromosomes were prepared using standard techniques.
      After 12 months, we undertook a second evaluation, this time with exposure to the
      same workers of 1.67 mSv/year. We observed 100 metaphases per subject, and there
      was a high percentage of altered metaphases (29.2% in the first sample and 26% in
      the second samples) The chromosome analysis in the second mitotic division, show
      aberrations such as gaps, breaks and acentric fragments, as well as other
      alterations such as dicentrics and rings, as well as chromosome variants (double
      minutes) in the exposed workers vs. the controls, and the difference was
      statistically highly significant (p < 0.001). There is no statistically
      significant difference between the first sample of exposed workers with the
      second one (p > 0.05). The findings in this study are interesting, because the
      workers were exposed to doses well below the accepted standards for exposure to
      radiations. Because of these unusual findings, our results could have potentially
      major consequences on our views on standards of exposure to radiation.

PMID- 8524340
TI  - Inhibition by capsaicin against cyclophosphamide-induced clastogenicity and DNA
      damage in mice.
AB  - We have demonstrated in an earlier paper that capsaicin, the pungent principle of
      red hot chili, has a potent anti-oxidant property that interferes with free
      radical involved mechanisms. In the present paper we demonstrate that capsaicin
      significantly inhibits cyclophosphamide-induced (i.p.) chromosomal aberrations
      and DNA strand breakages. This protective action of capsaicin against CP-induced
      toxicity may possibly be linked with its already reported 'desensitisation'
      effect against chemical irritant-induced damages.

PMID- 8524341
TI  - Genotoxic effects of the alpha, beta-unsaturated aldehydes 2-trans-butenal, 2
      trans-hexenal and 2-trans, 6-cis-nonadienal.
AB  - The genotoxic effects of the 2-alkenals crotonaldehyde, 2-trans-hexenal and 2
      trans-6-cis-nonadienal were studied by cytogenetic methods, analyzing frequencies
      of sister-chromatid-exchanges, numerical and structural chromosome aberrations
      and micronucleus induction in human blood lymphocytes and cells of the permanent
      Namalva line. Crotonaldehyde and hexenal were tested in concentrations of 5
      microM to 250 microM and nonadienal from 5 microM to 70 microM. Significant dose
      related increases of sister-chromatid-exchanges and micronuclei were found for
      all three compounds. Structural chromosomal aberrations were significantly
      increased only by crotonaldehyde, but not by hexenal and nonadienal. In contrast
      numerical chromosome aberrations were not induced by crotonaldehyde whereas
      hexenal and nonadienal were potent inducers of aneuploidy. The micronuclei were
      classified by using a centromere-specific DNA probe in a fluorescence in situ
      hybridization assay. Hexenal and nonadienal increased the percentage of
      centromere-positive micronuclei, nonadienal being considerably more potent than
      hexenal. From these results it was concluded that crotonaldehyde acts more as a
      clastogen whereas hexenal and nonadienal preferentially show aneugenic effects.

PMID- 8524342
TI  - Sister-chromatid exchanges, glutathione S-transferase theta deletion and
      cytogenetic sensitivity to diepoxybutane in lymphocytes from butadiene monomer
      production workers.
AB  - The magnitude of health risks to workers associated with current and past
      exposures to butadiene has been the subject of considerable recent debate.
      Butadiene is metabolized in-vivo and in-vitro to the genotoxic intermediates 3,4
      epoxybutene and diepoxybutane. Studies in animals and in-vitro systems have
      clearly demonstrated that 1,3-butadiene is a genotoxin and a potent inducer of
      sister-chromatid exchanges (SCEs). Data on the genotoxicity of butadiene in
      humans is, however, limited. Epidemiologic data indicate that butadiene is a
      probable human carcinogen. Recent work has further demonstrated that cultured
      lymphocytes from the approximately 20% of the Caucasian population that lack the
      glutathione S-transferase class theta gene (GSTT1) are relatively sensitive to
      the induction of cytogenetic damage by butadiene metabolites. In order to test
      whether butadiene exposure was associated with increases in SCE frequencies in
      peripheral blood lymphocytes and whether any increase observed could be affected
      by the DEB sensitivity-GSTT1 deletion, we studied 40 workers employed in the
      production of butadiene. In these workers baseline frequencies of SCEs,
      diepoxybutane-induced SCE frequencies and GSTT1 deletion status were assessed.
      Questionnaires were administered to each worker and exposure to 1,3-butadiene was
      determined using three separate approaches. Industrial hygiene personal sampling
      was used to measure breathing zone butadiene exposure and urine was collected to
      use in measurement of the urinary butadiene metabolite 1,2-dihydroxy-4-(N
      acetylcysteinyl-S-)-butane (M1). Exposure to butadiene was generally below 2 ppm.
      The urinary metabolite M1 was found in all workers, but it did not correlate
      significantly with exposure. Six of 40 of the workers were GST theta-deleted DEB
      sensitive. No measure of acute or chronic exposure to butadiene was associated
      with an increase in SCE frequency. However, smoking and DEB sensitivity-GSTT1
      null status were each significantly associated with elevations in baseline SCE
      frequency.

PMID- 8524343
TI  - Genotoxicity of nicotine and cotinine in the bacterial luminescence test.
AB  - Cotinine was positive in the absence of S9 in the bacterial luminescence
      genotoxicity test at 1.25 mg/ml (9-15 h incubation) and at 2.50 mg/ml (18-30
      incubation hours) signifying potential mutagenicity and teratogenicity. In the
      presence of S9, cotinine was positive at 1.25 mg/ml after 9 incubation hours. In
      contrast, nicotine was not at any concentration or incubation time.
      Nicotine/cotinine mixtures were still positive at physiological concentrations,
      with potentiation relative to cotinine alone with and without S9. Standard
      additions of nicotine to other positive controls such as 2-aminoanthracene (2AA)
      (a mutagen causing point mutations on activation), phenol (a DNA intercalator),
      and N-methyl-N'-nitrosoguanidine (MNNG) (a direct-acting point mutagen) revealed
      a complex nicotine effect. Nicotine antagonized MNNG without S9, and potentiated
      MNNG with S9, 2AA with and without S9, and phenol without S9. Cotinine was not a
      very potent agent relative to the positive controls. Since cotinine has been
      considered an inactive biological monitoring marker of nicotine absorption in
      humans, the present results indicate that the many health effect correlations
      based on cotinine in urine, serum, saliva, and blood may involve more cause and
      effect than thought hitherto.

PMID- 8524344
TI  - Monitoring of induced chromosomal aberrations in S. cerevisiae in agarose gels by
      pulsed field gel electrophoresis.
AB  - Pulsed field gel electrophoresis (PFGE) has been used to detect aberrations of
      the chromosomal banding pattern referred to as chromosomal aberrations arising
      after treatment of yeast strain S. cerevisiae MP1 with the three different
      genotoxic substances 4-nitroquinoline-N-oxide (4-NQO), methotrexate (MTX) and 2
      amino-6-mercaptopurine (AMP). Different chromosomal aberrations were detectable
      directly in the pulsed field gel when growing yeast cells were incubated with a
      genotoxin for 6 h at 26 degrees C followed by treatment with the genotoxin for
      another twelve days at 4 degrees C. In the present study, clones of yeast cells
      were examined. In this way, distinct chromosomal aberrations and not only DNA
      smear could be detected. Moreover, this method allows selection for yeast strains
      with specific and rare chromosomal rearrangements.

PMID- 8524345
TI  - Evaluation studies on the in vitro rat hepatocyte micronucleus assay.
AB  - Based on a previous study with 8 chemicals (Muller et al., 1993) the
      applicability of the in vitro rat hepatocyte micronucleus assay was evaluated by
      testing a further 21 compounds of different chemical classes. The obtained
      results are in good agreement with the known genotoxic profiles of about 90% of
      the in total tested compounds. Several known mutagens and carcinogens, i.e.,
      alkylating agents, aromatic amines, nitrosamines, nitro compounds, cross-linking
      agents, and pyrrolizidine alkaloids gave clear positive results in this assay,
      whereas all of the tested non-carcinogens were negative. The hepatocyte
      micronucleus assay was shown to distinguish between carcinogenic/non-carcinogenic
      isomers, such as 2- and 4-acetylaminofluorene (AAF) and 2- and 1-nitropropane
      (NP). Furthermore, the non-genotoxic nature of several hepatocarcinogens, i.e.,
      the peroxisome proliferating agents fenofibrate, nafenopin, Wy-14,643,
      diethyl(hexyl)phthalate (DEHP), and the sedative phenobarbital, could be
      confirmed in this assay. The hepatocarcinogen coumarin exerted mitogenic but no
      mutagenic properties in the rat hepatocyte micronucleus assay. This compound may
      act as a liver tumor promoter. Benzo[a]pyrene (B[a]P) and 7,12
      dimethylbenzanthacene (DMBA), both belonging to the group of known carcinogenic
      and mutagenic polycyclic aromatic hydrocarbons, failed to induce micronucleus
      formation in rat hepatocytes. The high susceptibility of in vitro proliferating
      hepatocytes to mitotic inhibition, exerted by the strong cytotoxic actions of
      these compounds, seems to be responsible for these negative results. A strongly
      reduced mitotic activity can prevent the formation of micronuclei, even when
      clastogenic effects may have occurred. In the present stage, the in vitro rat
      hepatocyte micronucleus assay cannot be recommended for screening genotoxicity
      testing. It should rather be used for special purposes, e.g., when liver-specific
      mutagenic effects are expected.

PMID- 8524346
TI  - Cryopreserved and hypothermically stored rat liver parenchymal cells as
      metabolizing system in the Salmonella mutagenicity assay.
AB  - Freshly isolated and preserved rat liver parenchymal cells were used as
      metabolizing system in the Salmonella mutagenicity assay. The liver cells were
      isolated with EDTA perfusion without the addition of collagenase and had a
      viability of 96% as judged by trypan blue exclusion. When freshly isolated liver
      parenchymal were cryopreserved with a computer controlled freezing protocol and
      stored at -196 degrees C they had a mean viability of 89% after thawing.
      Furthermore, freshly isolated cells were stored at 0 degree C in University of
      Wisconsin organ transplantation solution. After 1 day of hypothermic storage they
      had a viability of 95%. Four different indirect mutagens, 2-aminoanthracene,
      benzo[a]pyrene, 7,12-dimetylbenz[a]anthracene and cyclophosphamide, were used
      with the liver cells as metabolizing system in the preincubation assay with
      Salmonella typhimurium TA100. After cryopreservation, liver parenchymal cells
      were able to activate all tested indirect mutagens to ultimate mutagens. However,
      the induction of revertants was lower with three of the four tested compounds.
      Only 2-aminoanthracene was activated to the same extent by freshly isolated and
      cryopreserved liver cells. 7-Hydroxymethyl-12-methylbenz[a]anthracene, which is
      activated to its ultimate mutagen by sulfotransferase, also induced a reduced
      mutagenic effect with cryopreserved liver cells in comparison to freshly isolated
      liver parenchymal cells. This indicates that phase I and phase II enzyme
      activities are effected by cryopreservation. However, identical mutation
      frequencies were obtained when freshly isolated liver parenchymal cells or 1 day
      hypothermically preserved liver parenchymal cells were used in the cell-mediated
      Salmonella mutagenicity test. The use of hypothermic short-time storage of liver
      parenchymal cells could help to make the liver cell-mediated genotoxicity test
      simpler and thereby more attractive.

PMID- 8524347
TI  - Mutagenicity of airborne particulate organic material from urban and industrial
      areas of Sao Paulo, Brazil.
AB  - The mutagenicity of airborne particulate matter at three different sites within
      the Sao Paulo urban area and the Cubatao industrial area, Sao Paulo State,
      Brazil, was evaluated using the Salmonella mutagenicity assay over a year's
      period (June 1990-May 1991). Total suspended particles (TSP) were collected using
      a Hi-vol sampler and extracted with methylene chloride by ultrasonication. Pooled
      seasonal extracts were tested using S. typhimurium TA98 and TA100 with and
      without metabolic activation (S9) and TA98NR and TA98/1,8-DNP6 without metabolic
      activation. Organic extracts of the samples with the highest monthly TSP
      concentration were also assayed for mutagenicity. All samples collected at Sao
      Paulo and Cubatao showed mutagenicity with strain TA98, and in general the
      addition of S9 did not modify the mutagenic response, suggesting the prevalence
      of direct-acting frameshift mutagens in the atmosphere of these sites. The
      mutagenicity detected in the urban areas of Sao Paulo (mainly downtown) was much
      higher than in the Cubatao industrial area and similar to the more urbanized
      cities in the world, where vehicle emissions are the major pollution source.
      Results obtained with the strains TA98NR and TA98/1,8-DNP6 suggested the presence
      of mononitro- and dinitroarenes contributed to the mutagenicity of these
      atmospheric samples. A seasonal variation was observed with higher levels of
      frameshift mutagens during Spring in Sao Paulo and Summer in Cubatao. During the
      Winter, more significant responses were found with strain TA100 in the presence
      of S9 at all sites. Monthly samples presented high levels of mutagenicity during
      the period of June to November. Results from this research provide support for
      Air Pollution Control Programs in the detection of the more potent organic
      mutagenic compounds in the atmosphere and may help in the establishment of
      priorities for control and regulatory actions.

PMID- 8524348
TI  - Use of cyclophosphamide as a positive control in dominant lethal and micronucleus
      assays.
AB  - Analyses of dominant lethal (DL) mutations and micronuclei (MN) are 2 important
      and widely used genotoxicity assays to measure drug-induced chromosome damage in
      germ cells and somatic cells, respectively. Cyclophosphamide (CP) has been widely
      used as a positive control in the single-dose mouse MN assay; however, its
      utility as a positive control for the DL assay has not been fully studied. In the
      present study, CP was tested in both assays under similar experimental conditions
      and MN seen in somatic tissue (bone marrow) were correlated with DL mutations
      seen in germinal tissue. In a dose-range finding study, groups of 5 male mice
      were dosed i.p. daily for 5 days at 0, 30 or 40 mg/kg CP and bone marrow was
      harvested 24 h later for MN assay. CP induced a dose-related increase (7- and 11
      fold over control at 30 and 40 mg/kg) in micronucleated polychromatic
      erythrocytes (MNPCEs) and decreased %PCEs (to 60% and 54% of controls at 30 and
      40 mg/kg, respectively). Based on this, a definitive DL and MN study was
      conducted using separate groups of 30 male mice at 0 and 40 mg/kg CP with a daily
      times 5 dosing regimen. For the MN assay, bone marrow was collected 24 h after
      the last dose from 5 animals and evaluated for MNPCEs and %PCEs. For the DL
      assay, each male was caged with 2 untreated females per week for 8 weeks to cover
      the postmeiotic germ cell stages. On day 17 after the initiation of breeding, the
      females were evaluated for the number of implantation sites and live, dead and
      resorbed implants. The results indicated that CP induced about a 17-fold increase
      in MNPCEs and a 46% decrease in PCEs in relation to controls. In the DL assay, CP
      produced a slight (13%) but statistically significant reduction in fertility
      index at week 7 of mating. Also, the total number of implants was significantly
      lower during weeks 1, 2, 3, 6 and 7 and the numbers of dead implants and
      postimplantation loss (PIL) were increased for weeks 1, 2 and 3 (55%, 71% and 34%
      PIL, respectively) over controls. These data clearly show that CP produced
      clastogenicity and some toxicity in both somatic tissue and germinal tissue. It
      was concluded that a dose of 40 mg/kg CP can be used as a positive control
      compound in the DL assay and in the multiple-dose marrow MN assay.

PMID- 8524349
TI  - Genetic toxicology of trichloroethylene (TCE).

PMID- 8524350
TI  - Trenimon: structure and reactivity of a versatile chemical agent.

PMID- 8524351
TI  - Mutagenicity of nitrodibenzopyranones in the Salmonella plate-incorporation and
      microsuspension assays.

PMID- 8524352
TI  - Mutagenicity of nitro- and amino-substituted carbazoles in Salmonella
      typhimurium. II. Ortho-aminonitro derivatives of 9H-carbazole.

PMID- 8524353
TI  - Comparative mutagenicity testing of ceftiofur sodium: I. Positive results in in
      vitro cytogenetics.

PMID- 8524354
TI  - Comparative mutagenicity testing of ceftiofur sodium. II. Cytogenetic damage
      induced in vitro by ceftiofur is reversible and is due to cell cycle delay.

PMID- 8524355
TI  - Comparative mutagenicity testing of ceftiofur sodium: III. Ceftiofur sodium is
      not an in vivo clastogen.

PMID- 8524356
TI  - Inhibition of mutagenesis of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by
      coumarins and furanocoumarins, chromanones and furanochromanones.

PMID- 8524357
TI  - Cytogenetic evaluation of butylated hydroxytoluene.

PMID- 8524358
TI  - Comparison of DNA damage from genotoxicants using the microgel electrophoresis
      assay with primary cultures of rat and human hepatocytes.

PMID- 8524359
TI  - Genotoxicity evaluation of estradiol.

PMID- 8524360
TI  - The adaptive response of peripheral blood lymphocytes to low doses of mutagenic
      agents in patients with ataxia telangiectasia.
AB  - The inducible ability of adaptive response by low doses of gamma rays or
      bleomycin was studied in peripheral blood lymphocytes of healthy donors and in
      ataxia telangiectasia patients. An adaptive response was found in the lymphocytes
      of healthy donors pretreated with either gamma rays or bleomycin, however in
      individuals heterozygous for ataxia only bleomycin was effective. In the two
      ataxia telangiectasia homozygotes tested no adaptive response was found either
      after low-dose gamma rays or after bleomycin. The preliminary results indicate
      that the adaptive response might be influenced by various factors.

PMID- 8524361
TI  - Mutagenicity and clastogenicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)
      furanone (MX) in L5178Y/TK+/(-)-3.7.2C mouse lymphoma cells.
AB  - 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was tested without
      exogenous activation in L5178Y/TK+/(-)-3.7.2C mouse lymphoma cells for mutation
      at the thymidine kinase locus and for clastogenicity. At a concentration of 0.75
      micrograms/ml, the induced mutant frequency was 1027 per 10(6) survivors
      (survival = 11%). A concentration-related increase of large and small colony
      mutants was observed, but the majority of the MX induced mutants formed small
      colonies, consistent with the positive clastogenic response that was observed. MX
      primarily induced chromatid breaks and rearrangements (30 chromatid and 4
      chromosome aberrations per 100 cells) at the 0.75 microgram/ml dose. These
      studies indicate that MX induces a broad spectrum of genetic damage.

PMID- 8524362
TI  - Expression of the DNA repair gene XRCC1 in baboon tissues.
AB  - XRCC1 is a DNA repair gene involved in rejoining DNA strand-breaks. We used
      baboon as an animal model to determine the levels of XRCC1 gene expression in
      different tissues. Baboons were selected because they are evolutionarily closely
      related to humans. A single 2.2 kb transcript was detected in all tissues tested
      by northern blot analysis, with variations in levels of expression among tissues.
      The expression levels of XRCC1 were measured by quantitative RNase protection
      assays. XRCC1 mRNA levels were significantly higher in testis than those in other
      tissues. A mean value of 24.6 x 10(5) XRCC1 transcripts per micrograms DNA was
      found in testis, while 10.5 x 10(5) in ovary, 9.8 x 10(5) in brain, 8.5 x 10(5)
      in liver, 6.8 x 10(5) in kidney, 6.5 x 10(5) in heart, 6.4 x 10(5) in lymph
      nodes, 6.0 x 10(5) in lung and 4.9 x 10(5) in spleen were found.

PMID- 8524363
TI  - Effect of red cells and plasma blood in determining individual lymphocytes
      sensitivity to diepoxybutane assessed by in vitro induced sister chromatid
      exchanges.
AB  - Previous authors investigated individual responsiveness to mutagens by assessing
      cytogenetic damage following in vitro treatment. Diepoxybutane (DEB) has been
      used to assess chromosome instability both in repair-deficient and normal
      subjects. Since bimodal distribution of sister chromatid exchanges (SCEs) or
      chromosomal aberration (CAs) frequencies has been observed in normal subjects, we
      investigated the possible factors determining the 'high-respondent' phenotype.
      The bimodal-shaped distribution suggested the presence of a single factor
      responsible far this phenotype. Our data showed that red blood cells are involved
      in determining the sensitivity of lymphocytes to DEB induced SCE. The existence
      of a polymorphic factor in red cells involved in DEB detoxification is suggested.

PMID- 8524364
TI  - Comparison of gamma-ray induced dicentric yields in human lymphocytes measured by
      conventional analysis and FISH.
AB  - In an earlier work stable aberrations and dicentrics were determined by
      fluorescence in situ hybridization (FISH) after various doses of 137Cs gamma
      rays. No corresponding calibration curve for dicentrics is available for
      determinations in terms of the conventional analysis as performed in our
      laboratory. In view of the potential for the application of chromosome painting
      to human biological dosimetry, it is desirable to determine such a calibration
      curve and this and the comparison of the resulting data to those obtained in
      terms of the FISH method is the objective of the present communication. In the
      study it is found that the linear-quadratic dose response curves for dicentrics,
      that are determined by the two methods, are significantly different, although the
      different target sizes are accounted for. A similar problem was found earlier for
      X-rays. It does not appear that the difference is due to technical difficulties
      in the FISH method, that has been improved by employing in addition to the whole
      chromosome DNA probes, a pan-centromeric DNA probe.

PMID- 8524365
TI  - Interferon-alpha or beta potentiate platinum analogous in human glioblastoma cell
      lines.
AB  - The effect of interferon-alpha or beta on platinum analogues [cisplatin (CDDP)
      and carboplatin] cytotoxicity was studied in four glioblastoma cell lines
      (U373MG, T98G, A172 and U118Mg). All cell lines were strongly resistant to the
      cytotoxic effect of CDDP or carboplatin. Although both interferons were not
      cytotoxic in all cell lines, they were able to significantly increase the cell
      platinum-sensitivity. Specifically interferon-alpha increased the magnitude of
      CDDP-induced DNA interstrand crosslinks. Our findings suggest that interferons
      are able to induce a very strong potentiation of platinum analogues cytotoxicity
      in drug-resistant human glioma cell lines.

PMID- 8524366
TI  - Mutagenicity of nitrobenzyl derivatives: potential bioreductive anticancer
      agents.
AB  - Ortho-, meta- and para-nitrobenzyl bromides, alcohols, ethers and esters were
      synthesised and tested for their mutagenicity toward Salmonella typhimurium
      TA100, TA100NR (nitroreductase deficient) and TA98 in absence of S9 mix and in
      TA100 with S9 mix. Compounds of the ortho- and meta-series were non mutagenic
      with and without S9 mix. Except for the alcohol and ether, the compounds of the
      para-series were mutagenic in TA100 with activity sequence propionate > butyrate
      > benzoate > acetate > bromide and this specific activity was reduced
      considerably by S9 mix. The Ames Salmonella test system does not seem to be an
      appropriate model to evaluate mutagenicity of o-nitrobenzyls. However, further
      work is in progress to test all the compounds for mutagenicity in mammalian
      system.

PMID- 8524367
TI  - Valediction from an old hand.

PMID- 8524368
TI  - Genome research risks abuse, panel warns.

PMID- 8524369
TI  - Medical rivals consider joint operations.

PMID- 8524370
TI  - AIDS survey traces shifting attitudes.

PMID- 8524371
TI  - Rabbit virus threatens ecology after leaping the fence.

PMID- 8524372
TI  - Anticancer drugs.

PMID- 8524373
TI  - Patents and indigenous lore.

PMID- 8524374
TI  - Patents and indigenous lore.

PMID- 8524375
TI  - Restoring good manners.

PMID- 8524377
TI  - Science in China.

PMID- 8524376
TI  - The case for genomic patenting.
AB  - Opposition to the patenting of genomic inventions threatens to erode the
      foundation of intellectual property rights needed to convert innovative research
      into new drugs, vaccines and diagnostic tests.

PMID- 8524378
TI  - When is prenatal diagnosis 'eugenics'?

PMID- 8524379
TI  - Contention over growth promoters.

PMID- 8524380
TI  - Cell biology. A nice ring to the centrosome.

PMID- 8524381
TI  - Jeffries Wyman (1901-95)

PMID- 8524382
TI  - Bloom's syndrome. Mapping to the point.

PMID- 8524383
TI  - Plant biology. At the roots of nutrition.

PMID- 8524384
TI  - HIV. An elusive soluble suppressor.

PMID- 8524385
TI  - Planetary science. Probing times for Jupiter.

PMID- 8524386
TI  - HIV suppression by interleukin-16.

PMID- 8524387
TI  - Tetrodotoxin as a pheromone.

PMID- 8524388
TI  - Ovalocytosis and cerebral malaria.

PMID- 8524389
TI  - Extrapolation or attention shift?

PMID- 8524390
TI  - Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex.
AB  - The highly conserved protein gamma-tubulin is required for microtubule nucleation
      in vivo. When viewed in the electron microscope, a highly purified gamma-tubulin
      complex from Xenopus consisting of at least seven different proteins is seen to
      have an open ring structure. This complex acts as an active microtubule
      nucleating unit which can cap the minus ends of microtubules in vitro.

PMID- 8524391
TI  - Structure and ligand recognition of the phosphotyrosine binding domain of Shc.
AB  - The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB)
      domain of Shc complexed to a phosphopeptide reveals an alternative means of
      recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the
      phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the
      protein, interacts with a hydrophobic pocket through the (pY-5) residue, and
      adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology
      domains (a beta-sandwich capped by an alpha-helix) and binds to acidic
      phospholipids, suggesting a possible role in membrane localization.

PMID- 8524392
TI  - Generation of lightning in Jupiter's water cloud.
AB  - Lightning is a familiar feature of storms on the Earth, and has also been seen on
      Jupiter and inferred indirectly to occur on Venus and Neptune. On Jupiter,
      lightning may be important as a source of energy to drive chemical reactions in
      the atmosphere, perhaps determining the abundances of molecules such as CO, HCN
      and C2H2. Lightning may be generated in Jupiter's water clouds by a mechanism
      similar to that which operates in terrestrial thunderstorms. Here we investigate
      the development of lightning by modelling the thunderstorm separation of
      electrical charge on precipitating ice particles at varying depths in Jupiter's
      atmosphere. We find that lightning can indeed be generated in the jovian water
      clouds, and that--in agreement with estimates from the analysis of Voyager images
      -it is most likely to occur at the 3- or 4-bar pressure level. Our model also
      predicts that a condensed-water abundance in the range of at least 1-2 g m-3 is
      required for lightning to occur in jovian thunderstorms--a prediction that may be
      tested when the Galileo probe arrives at Jupiter on 7 December 1995.

PMID- 8524393
TI  - Unexpected dominance of high frequencies in chaotic nonlinear population models.
AB  - Because water has a higher heat capacity than air, large bodies of water
      fluctuate in temperature more slowly than does the atmosphere. Marine temperature
      time series are 'redder' than atmospheric temperature time series by analogy to
      light: in red light, low-frequency variability has greater amplitude than high
      frequency variability, whereas in white light all frequencies have the same
      amplitude. Differences in the relative importance of high-and low-frequency
      variability in different habitats affect the population dynamics of individual
      species and the structure of ecological communities. Population dynamics of
      individual species are thought to be dominated by low-frequency fluctuations,
      that is, to display reddened fluctuations. Here I report, however, that in eight
      nonlinear, iterative, deterministic, autonomous, discrete-time population models,
      some of which have been used to model real biological populations, the power
      spectral densities of chaotic trajectories are neither white nor reddened but are
      notably blue, with increasing power at higher frequencies.

PMID- 8524394
TI  - Visually evoked calcium action potentials in cat striate cortex.
AB  - Early intracellular studies of cerebral cortical neurons indicated that synaptic
      input evokes dendritic action potentials that convey information towards the
      soma. Subsequent work in vitro established that neocortical neurons produce
      dendritic Ca2+ action potentials. To determine whether natural stimuli elicit
      Ca2+ spikes, we combined the techniques of whole-cell recording, pharmacology and
      quantitative receptive field mapping. Our findings show that visual stimulation
      routinely evoked Ca2+ spikes in distinct functional and anatomical classes of
      cells in different layers of the cat striate cortex. Hence regenerative Ca2+
      potentials appear to play a role in both the initial and later stages of cortical
      sensory processing.

PMID- 8524395
TI  - Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand.
AB  - Lack of functional expression of CD40 ligand (CD40L) on T cells results in hyper
      IgM syndrome (HIGM1), a human immunodeficiency associated with a severely
      impaired humoral immune response that is consistent with defects in B-cell
      responses. Patients also succumb to recurrent opportunistic infections such as
      Pneumocystis carinii and Cryptosporidial diarrhoea, suggesting that T-cell
      functions are also compromised in these individuals, but so far this has not been
      explained. We have previously shown that mice deficient for CD40L, like HIGM1
      patients, show grossly abnormal humoral responses. Here we report that CD40L
      deficient mice are defective in antigen-specific T-cell responses. Adoptively
      transferred antigen-specific CD4+ T cells lacking CD40L failed to expand upon
      antigen challenge of the recipients, showing that expression of CD40L on T cells
      is required for in vivo priming of CD4+ T cells and therefore for the initiation
      of specific T-cell immune responses.

PMID- 8524396
TI  - CD40 ligand-transduced co-stimulation of T cells in the development of helper
      function.
AB  - Mice that lack either CD40 (expressed on B cells) or CD40 ligand (expressed on
      activated T cells) are able neither to make IgG, IgA or IgE antibody responses,
      nor to generate germinal centres (the sites of formation of memory B cells). It
      has been assumed that these lesions were the result of an absence of signals to B
      cells through CD40. Here we show that the failure to signal T cells through CD40
      ligand is an important contributory cause. Administration of soluble CD40 in vivo
      to CD40 knockout mice, restoring the missing signal through CD40 ligand initiates
      germinal centre formation. Furthermore, T cells primed in the absence of CD40 (in
      CD40 knockout mice) are unable to help normal B cells to class switch or to form
      germinal centres (GC). These results indicate that co-stimulation of T cells
      through CD40 ligand causes their differentiation into cells that help B cells to
      make mature antibody responses and to generate memory populations.

PMID- 8524397
TI  - Functional impact of syntaxin on gating of N-type and Q-type calcium channels.
AB  - Rapid and reliable synaptic transmission depends upon the close proximity of
      voltage-gated calcium channels and neurotransmitter-containing vesicles in the
      presynaptic terminal. Although it is clear that a local Ca2+ rise conveys the
      crucial signal from Ca2+ channels to the exocytotic mechanism, little is known
      about whether communication ever proceeds in the opposite direction, from the
      release machinery to Ca2+ channels. To look for such signalling, we examined the
      interaction of various types of voltage-gated Ca2+ channels with syntaxin, a
      presynaptic membrane protein of relative molecular mass 35,000 which may play a
      key part in synaptic vesicle docking and fusion and which interacts strongly with
      N-type Ca2+ channels. Here we report that co-expression of syntaxin 1A with N
      type channels in Xenopus oocytes sharply decreases the availability of these
      channels. This is due to the stabilization of channel inactivation rather than to
      a simple block or lack of channel expression, because it is overcome by strong
      hyperpolarization. Deletion of syntaxin's carboxy-terminal transmembrane domain
      abolishes its functional effect on Ca2+ channels. Syntaxin produced a similar
      effect on Q-type Ca2+ channels encoded by alpha 1A but not on L-type Ca2+
      channels. Thus, the syntaxin effect is specific for Ca2+ channel types that
      participate in fast transmitter release in the mammalian central nervous system.
      We hypothesize that, in addition to acting as a vesicle-docking site, syntaxin
      may influence presynaptic Ca2+ channels, opposing Ca2+ entry where it is not
      advantageous, but allowing it at release sites where synaptic vesicles have
      become docked and/or ready for fusion.

PMID- 8524398
TI  - A phosphate transporter from the mycorrhizal fungus Glomus versiforme.
AB  - Vesicular-arbuscular (VA) mycorrhizal fungi form symbiotic associations with the
      roots of most terrestrial plants, including many agriculturally important crop
      species. The fungi colonize the cortex of the root to obtain carbon from their
      plant host, while assisting the plant with the uptake of phosphate and other
      mineral nutrients from the soil. This association is beneficial to the plant,
      because phosphate is essential for plant growth and development, especially
      during growth under nutrient-limiting conditions. Molecular genetic studies of
      these fungi and their interaction with plants have been limited owing to the
      obligate symbiotic nature of the VA fungi, so the molecular mechanisms underlying
      fungal-mediated uptake and translocation of phosphate from the soil to the plant
      remain unknown. Here we begin to investigate this process by identifying a
      complementary DNA that encodes a transmembrane phosphate transporter (GvPT) from
      Glomus versiforme, a VA mycorrhizal fungus. The function of the protein encoded
      by GvPT was confirmed by complementation of a yeast phosphate transport mutant.
      Expression of GvPT was localized to the external hyphae of G. versiforme during
      mycorrhizal associations, these being the initial site of phosphate uptake from
      the soil.

PMID- 8524399
TI  - Role of auxilin in uncoating clathrin-coated vesicles.
AB  - Clathrin-coated vesicles transport selected integral membrane proteins from the
      cell surface and the trans-Golgi network to the endosomal system. Before fusing
      with their target the vesicles must be stripped of their coats. This process is
      effected by the chaperone protein hsp70c together with a 100K cofactor which we
      here identify as the coat protein auxilin. Auxilin binds with high affinity to
      assembled clathrin lattices and, in the presence of ATP, recruits hsp70c.
      Dissociation of the lattice does not depend as previously supposed on clathrin
      light chains or on the amino-terminal domain of the heavy chain. The presence of
      a J-domain at its carboxy terminus now defines auxilin as a member of the DnaJ
      protein family. In conjunction with hsp70, DnaJ proteins catalyse protein
      folding, protein transport across membranes and the selective disruption of
      protein-protein interactions. We show that deletion of the J-domain of auxilin
      results in the loss of cofactor activity.

PMID- 8524400
TI  - Actin-based motility of vaccinia virus.
AB  - The role of the cytoskeleton during viral infection is poorly understood. Here we
      show, using a combination of mutant and drug studies, that the intracellular
      enveloped form of vaccinia virus is capable of inducing the formation of actin
      tails that are strikingly similar to those seen in Listeria, Shigella and
      Rickettsia infections. Analysis using video microscopy reveals that single viral
      particles are propelled in vivo on the tip of actin tails, at a speed of 2.8
      mumol min-1. On contact with the cell surface, virus particles extend outwards on
      actin projections at a similar rate, to contact and infect neighboring cells.
      Given the similarities between the motility of vaccinia virus and bacterial
      pathogens, we suggest that intracellular pathogens have developed a common
      mechanism to exploit the actin cytoskeleton as a means to facilitate their direct
      spread between cells.

PMID- 8524401
TI  - Microtubule nucleation by gamma-tubulin-containing rings in the centrosome.
AB  - The microtubule cytoskeleton of animal cells does not assemble spontaneously, but
      instead requires the centrosome. This organelle consists of a pair of centrioles
      surrounded by a complex collection of proteins known as the pericentriolar
      material (PCM). The PCM is required for microtubule nucleation. The minus, or
      slow-growing, ends of microtubules are embedded in the PCM and the plus, or fast
      growing, ends project outwards into the cytoplasm during interphase, or into the
      spindle apparatus during mitosis. gamma-Tubulin is the only component of the PCM
      that is so far implicated in microtubule nucleation. Here we use immuno-electron
      microscopic tomography to show that gamma-tubulin is localized in ring structures
      in the PCM of purified centrosomes without microtubules. When these centrosomes
      are used to nucleate microtubule growth, gamma-tubulin is localized at the minus
      ends of the microtubules. We conclude that microtubule-nucleating sites within
      the PCM are ring-shaped templates that contain multiple copies of gamma-tubulin.

PMID- 8524402
TI  - Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin
      complex.
AB  - Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine
      phosphate which is critical for several important cellular processes, including T
      cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A
      and FK506, which inhibit CaN after forming complexes with cytoplasmic binding
      proteins (cyclophilin and FKBP12, respectively). We report here the crystal
      structures of full-length human CaN at 2.1 A resolution and of the complex of
      human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an
      auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site
      geometry and active-site water structure suggest a catalytic mechanism involving
      nucleophilic attack on the substrate phosphate by a metal-activated water
      molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is
      displaced from the active site. The site of binding of FKBP12-FK506 appears to be
      shared by other non-competitive inhibitors of calcineurin, including a natural
      anchoring protein.

PMID- 8524403
TI  - Non-invasive ion probes--tools for measuring transmembrane ion flux.
AB  - Ionophores, used in non-invasive vibrating electrodes, can directly monitor
      steady-state ion flux from single cells, even when the source is non
      electrogenic.

PMID- 8524404
TI  - AIDS patient given baboon bone marrow.

PMID- 8524405
TI  - European proposal reopens debate over patenting of human genes.

PMID- 8524406
TI  - NIH denies blame for radiation poisoning but tightens rules.

PMID- 8524407
TI  - BSE results 'may quell panic', but caution still needed.

PMID- 8524408
TI  - Mice and beef and brain diseases.
AB  - Can people contract neurodegenerative disease by eating beef products
      contaminated with bovine spongiform encephalopathy? Experiments with transgenic
      mice give cause to think that the answer may be 'no'.

PMID- 8524409
TI  - Breast cancer genes. Further enigmatic variations.

PMID- 8524410
TI  - Apoptosis and increased generation of reactive oxygen species in Down's syndrome
      neurons in vitro.
AB  - Down's syndrome (DS) or trisomy 21 is the most common genetic cause of mental
      retardation. Development of the DS brain is associated with decreased neuronal
      number and abnormal neuronal differentiation, and adults with DS develop
      Alzheimer's disease. The cause of the neurodegenerative process in DS is unknown.
      Here we report that cortical neurons from fetal DS and age-matched normal brain
      differentiate normally in culture, but DS neurons subsequently degenerate and
      undergo apoptosis whereas normal neurons remain viable. Degeneration of DS
      neurons is prevented by treatment with free-radical scavengers or catalase.
      Furthermore, DS neurons exhibit a three- to fourfold increase in intracellular
      reactive oxygen species and elevated levels of lipid peroxidation that precede
      neuronal death. These results suggest that DS neurons have a defect in the
      metabolism of reactive oxygen species that causes neuronal apoptosis. This defect
      may contribute to mental retardation early in life and predispose to Alzheimer's
      disease in adults.

PMID- 8524411
TI  - Unaltered susceptibility to BSE in transgenic mice expressing human prion
      protein.
AB  - Prion diseases are transmissible neurodegenerative conditions of humans and
      animals. Prions consist principally of a post-translationally modified form of
      prion protein (PrP), PrP(Sc), which is partly protease resistant. Transmission of
      prion diseases between species is limited by a 'species barrier' determined in
      part by the degree of sequence homology between host PrP and inoculated PrP(Sc)
      (ref.3) and by prion strain type. The epidemic of bovine spongiform
      encephalopathy (BSE) in the United Kingdom and other countries has led to
      concerns that transmission to humans may occur by dietary exposure. BSE appears
      to be caused by a single strain, distinct from those of natural or experimental
      scrapie, which is also seen in the new prion diseases of cats and ruminants that
      have presumably arisen from dietary BSE exposure. Here we show that transgenic
      mice expressing human PrP in addition to mouse PrP can generate human PrP(Sc) and
      'human' prions. These mice therefore provide a model to study experimentally the
      species barrier limiting BSE transmission to humans. Incubation periods to BSE in
      transgenic mice are not shortened by expression of human PrP, and only mouse
      PrP(Sc) is produced in response to such challenge.

PMID- 8524412
TI  - Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland.
AB  - Formation of the pineal gland hormone melatonin increases markedly at night in
      response to light-dark environmental alterations. Melatonin is synthesized from
      serotonin by an initial N-acetylation followed by methylation of the 5-hydroxy
      moiety by hydroxyindole-O-methyltransferase. Serotonin N-acetyltransferase (NAT;
      EC2.3.1.87), which catalyses the first reaction, is the rate-limiting enzyme in
      this process, and its activity increases dramatically with the onset of darkness.
      Because melatonin may play important biological roles in reproduction, ageing and
      sleep, understanding the molecular factors that regulate NAT is of particular
      importance. To identify proteins that regulate light-dark variations in pineal
      function, we used a subtractive hybridization technique based on the polymerase
      chain reaction (PCR) to isolate rat pineal gland messages that are differentially
      expressed by day and night. Here we report the molecular cloning of NAT and
      dramatic diurnal variations in its transcription. Independently, Klein and
      associates have cloned NAT from sheep pineal glands.

PMID- 8524413
TI  - Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
AB  - Glycogen synthase kinase-3 (GSK3) is implicated in the regulation of several
      physiological processes, including the control of glycogen and protein synthesis
      by insulin, modulation of the transcription factors AP-1 and CREB, the
      specification of cell fate in Drosophila and dorsoventral patterning in Xenopus
      embryos. GSK3 is inhibited by serine phosphorylation in response to insulin or
      growth factors and in vitro by either MAP kinase-activated protein (MAPKAP)
      kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k). Here we
      show, however, that agents which prevent the activation of both MAPKAP kinase-1
      and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of
      GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these
      conditions, and we demonstrate that it is the product of the proto-oncogene
      protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs
      10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol
      (PI) 3-kinase.

PMID- 8524414
TI  - Identification of the breast cancer susceptibility gene BRCA2.
AB  - In Western Europe and the United States approximately 1 in 12 women develop
      breast cancer. A small proportion of breast cancer cases, in particular those
      arising at a young age, are attributable to a highly penetrant, autosomal
      dominant predisposition to the disease. The breast cancer susceptibility gene,
      BRCA2, was recently localized to chromosome 13q12-q13. Here we report the
      identification of a gene in which we have detected six different germline
      mutations in breast cancer families that are likely to be due to BRCA2. Each
      mutation causes serious disruption to the open reading frame of the
      transcriptional unit. The results indicate that this is the BRCA2 gene.

PMID- 8524415
TI  - Cloning and functional expression of a rat heart KATP channel.

PMID- 8524416
TI  - [Cell damage as reason for the formation of unsaturated fatty acid
      hydroperoxides].
AB  - In diseases leading to massive acute cell damage, e.g., myocardial infarction or
      spontaneous inflammation, increased amounts of hydroperoxides of unsaturated
      fatty acids (LOOH) are found. An even higher production of LOOH is observed in
      homogenized tissue. If cells are injured, dormant lipoxygenases (LOX) are
      inevitably activated. They oxidize unsaturated membrane fatty acids to LOOH. This
      process involves not only arachidonic acid - as tacitly assumed up to now - but
      also linoleic acid. LOOH are decomposed to chemically highly reactive species,
      some of which were previously unknown (e.g, alpha-hydroxyaldehydes). LOO.
      radicals can also transform any molecule with a double bond to an epoxide.
      Therefore, epoxides are found in injured tissue. The same degradation products of
      hydroperoxides have been observed in elevated amounts in acute cell injury and in
      chronic diseases, e.g., atherosclerosis, psoriasis, and rheumatoid diseases.
      Therefore, we conclude that in these cases too, increased generation of
      hydroperoxides is caused by gradual cell injury liberating lipoxygenases.

PMID- 8524417
TI  - Artificial neural networks in the analysis of behavioral topology.

PMID- 8524418
TI  - ['Office' or 'white-coat hypertension'].

PMID- 8524419
TI  - [Reinstatement of calcium-containing antacids].

PMID- 8524420
TI  - [Application of protons in the treatment of malignant tumors].

PMID- 8524421
TI  - [100 years of radiology in The Netherlands. IV. Radiotherapy, current status].

PMID- 8524422
TI  - [100 years of radiology in The Netherlands. V. Radiotherapy, future
      developments].

PMID- 8524423
TI  - [Local recurrence following breast-conserving treatment for breast carcinoma;
      treatment and prognosis in 82 patients].
AB  - OBJECTIVE: To evaluate the treatment and prognosis of 82 patients with local
      relapse in the breast as the first event after breast-conserving therapy of
      operable breast cancer. DESIGN: Descriptive and retrospective. SETTING: 17
      general hospitals in southeast North-Brabant and North-Limburg. METHODS: Using
      the registries of the Comprehensive Cancer Centre South in Eindhoven (1981-1990)
      and the Bernard Verbeeten Institute in Tilburg (1981-1987), 82 patients were
      identified who had developed local recurrence after breast-conserving therapy.
      RESULTS: The mean age of the 82 patients at the time of detection of local
      recurrence was 51 years. 46 recurrences (56%) were localized at or near the site
      of the original tumour, 14 (17%) were detected elsewhere in the breast, 15 (18%)
      showed diffuse spread through the breast and seven (9%) were completely or partly
      localized in the skin. Nine recurrences (11%) were non-invasive. Of the 82
      patients four received adjuvant systemic therapy only and no surgery. Of the 78
      patients treated with surgery 72 underwent mastectomy, 6 local excision. After
      treatment, the actuarial five-year overall survival, distant recurrence-free
      survival and disease-free survival rates were 60%, 43% and 31% respectively.
      Local control, defined as survival without second local recurrence and without
      local progression of the disease, was 57% after five years. CONCLUSION: The five
      year distant recurrence-free and disease-free survival rates for patients with
      local recurrence after breast conserving-therapy were low. The high proportion of
      second local recurrences and local progression of disease in this study
      underlines the difficulty of obtaining local control after treatment of local
      recurrence.

PMID- 8524424
TI  - [Radiotherapy following breast-conserving surgery: more local recurrences after
      longer delay].
AB  - OBJECTIVE: Evaluation of results of breast conserving therapy in early stage
      breast cancer and of importance of time interval between surgery and
      radiotherapy. DESIGN: Descriptive study. LOCATION: Free University Hospital,
      Amsterdam. METHOD: In the period 1980-1989, 554 patients with 560 invasive breast
      cancers were referred for radiotherapy after wide local excision of the tumour
      with axillary lymph node dissection. The dose to the breast was 50 Gy + 15 Gy
      boost dose. In case of positive margins, a higher boost dose (20-25 Gy) was
      given. Node-positive patients received adjuvant chemotherapy (premenopausal
      patients) or hormonal therapy (postmenopausal patients). RESULTS: The median
      follow-up period was 82 months (range 52-160 months). The 5 and 10-year survival
      rates were 86.7% and 72.6%, respectively. Local (breast) relapse occurred in 22
      patients (3.9%). The breast recurrence rate was 8/329 (2.4%) for patients who
      started radiotherapy within 7 weeks after surgery, as against 14/231 (6.1%) for
      patients with a longer interval (p < 0.05). In Cox's proportional hazards
      analysis, age (negative relation), T-stage and interval between surgery and
      radiotherapy were identified as independent factors predictive of breast
      recurrence (p < 0.05). CONCLUSION: A delay of radiotherapy after breast
      conserving surgery of more than 7 weeks can adversely affect the local tumour
      control rate.

PMID- 8524425
TI  - [Recurrence of reflux esophagitis can be prevented with maintenance therapy with
      sucralfate].
AB  - OBJECTIVE: To determine whether the recurrence of reflux oesophagitis can be
      prevented with sucralfate suspension 2 g daily. DESIGN: Double-blind, placebo
      controlled, multinational drug study. SETTING: Sixteen research centres in
      Switzerland, Germany and the Netherlands. METHOD: 184 Patients whose earlier
      reflux oesophagitis Savary-Miller grades I and II were cured by an antisecretory
      therapy before being included in the study. For 6 months, they were given 2 g of
      a sucralfate suspension or a placebo twice daily, with random division. The
      symptoms were checked monthly. Endoscopy was performed at the end of the study or
      when there was a clinical suspicion of recurrence. RESULTS: Eighty-eight patients
      of the sucralfate group and 93 of the placebo group could be evaluated. The
      proportion of endoscopical recurrence was significantly reduced (31 in the
      sucralfate group as against 55 in the placebo group; p < 0.001). This decrease
      was particularly clear where symptomatic recurrences were concerned (10 and 34%,
      respectively; p < 0.001). CONCLUSION: This is the first trial that demonstrates
      that sucralfate suspension can prevent recurrences of reflux oesophagitis in
      patients with solitary or confluent erosions previously cured with an
      antisecretory therapy.

PMID- 8524426
TI  - [Agranulocytosis caused by clozapine: the importance of leukocyte monitoring and
      efficacy of hematopoietic growth factors].
AB  - In four patients, a woman aged 85 and three men aged 33, 42 and 70 years,
      clozapine-induced agranulocytosis was diagnosed. In three patients the white cell
      counts were not performed as they should have been. Two patients were treated for
      their agranulocytosis with granulocyte colony-stimulating factor (G-CSF;
      filgrastim). Two patients were not treated. The literature concerning clozapine
      induced agranulocytosis and its treatment with growth factors consists of only a
      few case reports. Therefore a definite conclusion about the efficacy of the
      treatment for this particular indication is not yet possible.

PMID- 8524427
TI  - [100 years of radiology in The Netherlands. VI. Radiotherapy, a historic
      overview].

PMID- 8524428
TI  - [Home care: between idea and reality].

PMID- 8524429
TI  - [Surgical treatment of lymphadenitis caused by non-tuberculous mycobacteria in
      children].

PMID- 8524430
TI  - [Minor symptoms in family medicine: smegma and physiological phimosis].

PMID- 8524431
TI  - [Surgical treatment of lymphadenitis caused by non-tuberculous mycobacteria in
      children].

PMID- 8524432
TI  - [Minor symptoms in family medicine: smegma and physiological phimosis].

PMID- 8524433
TI  - [Treatment of keloids of the ear lobe].

PMID- 8524434
TI  - [Risk of breast carcinoma due to 'the pill' should not be exaggerated].

PMID- 8524435
TI  - "Changing times".

PMID- 8524436
TI  - Medicare reform: what's good for the goose is good for the gander.

PMID- 8524437
TI  - Balloon expandable intravascular stent in infrarenal aortic stenosis.

PMID- 8524438
TI  - Computerized medical data.

PMID- 8524439
TI  - Perinatal approach to skeletal dysplasia.

PMID- 8524440
TI  - Ask a lawyer.

PMID- 8524441
TI  - [Surgery for meningioma of the posterior skull base. 135 cases. Choice of
      approach and results].
AB  - One hundred and thirty-five patients with posterior skull base meningiomas were
      seen and treated by a neurosurgical-neurotological team over the last 12 years.
      Ten tumors were "true" clival meningiomas and 125 were posterior petrous
      meningiomas: 25 were located anterior to the internal auditory meatus (IAM) (zone
      A); 29 were located around the IAM (zone M) and 18 were posterior to the IAM
      (zone P). 53 tumors had a larger zone of implantation and are accordingly called
      AM (31 cases), MP (15 cases), AMP (7 cases). The choice of routes was guided by a
      radiological anatomy classification system (17). Transpetrous approaches, alone
      or in combination with subtemporal transtentorial or retrosigmoid approaches were
      the surgical routes of choice for posterior petrous meningiomas, making it
      possible to reach the tumoral osteodural implantation, reduce the tumoral mass
      and perform a subarachnoidal dissection of the tumor poles. A retrolabyrinthine
      (RL) approach allows access to zone P and a translabyrinthine approach to zone
      MP. Zones A, M and P can be reached via the anterior extended translabyrinthine
      (AETL) approach. Anterolateral transclival approaches with apex petrectomy were
      used to reach the clival meningiomas with a wide implantation zone. Standard
      microsurgical techniques were used in 32 cases and 103 procedures included the
      use of a microscope-guided laser. Complete tumor removal was accomplished in 88%
      of cases (120/135). Overall mortality was 3.7% (2 cases at 30 days and 3 cases
      between 31 days and 1 year).

PMID- 8524442
TI  - [The posterior part of the skull. Classification of dysmorphism. Original
      treatment: turned biparietal flap transposition].
AB  - The deformation of the posterior part of the skull (occipito-vertebral region),
      induced directly or indirectly, occurs in numerous pathological situations. Its
      significance is frequently overlooked. Lesions of the cranial content,
      alterations of the lambdoid suture or other premature synostosis, abnormal
      constraint related to posture or to muscular activity can modify the posterior
      curvature of the skull, generally flattening it. The authors propose a
      classification based on three points: -Intracranial pathology: alterations of the
      brain or CSF fluid can induce either insufficient (microencephaly) or excessive
      (hydrocephalus, Dandy Walker or Arnold Chiari malformations) expansion. -Bone
      pathology: craniosynostosis: sagittal synostosis (scaphocephaly) induces a
      bulging and coronal synostosis a flatness of the posterior skull. Bilateral
      premature lambdoid synostosis (pachycephaly) produces total flatness of the back
      of the skull. -Extrinsic pathology: dysmorphism is often asymmetrical and results
      from extracranial mechanical application dysfunction such as inborn torticollis,
      cervical spine pathology (Klippel-Feil syndrome), or prolonged decubitus during
      the first year of life. The authors describe a personal technique for correcting
      this dysmorphism: the turned biparietal flap transposition. The back of the skull
      is remodelled (either asymmetrical or bilateral flatness), and patients with no
      need for a helmet can lie on their backs immediately after the operation.

PMID- 8524443
TI  - [Anal migration of ventriculo-peritoneal shunt catheter. Apropos of 3 cases].
AB  - Three cases of abdominal catheter migration through the anus following ventriculo
      peritoneal shunt are described. Two cases involved hydrocephalus secondary to
      tuberculous meningitis and the third myelomeningocele. Among the reasons for
      migration, the length of the abdominal catheter, trauma during the operation and
      infection must be taken into consideration. One patient was suffering from
      meningitis at the time of admission, while the two others were asymptomatic.
      Treatment involved removing the peritoneal catheter in 2 cases and the entire
      shunt system in the patient with meningitis. The shunt was replaced one to two
      weeks later. The outcome was favourable in all three cases.

PMID- 8524444
TI  - [Subdural empyema. Apropos of 17 cases].
AB  - Seventeen patients with subdural empyema were treated from 1985 to 1993. These
      included 13 males and 4 females with 11 patients aged between 12 and 30 years
      old. Sinusitis was found to be the primary source of infection in 16 cases. The
      clinical presentation was classic and the preoperative diagnosis was established
      on the first CT in 12 cases. In the remaining cases a second or third CT was
      necessary to demonstrate the empyema, 24 to 48 hours later. Surgical management
      was first made by burr holes with a small craniectomy in 15 cases. A large
      craniotomy was performed in 2 patients. Soft catheter drainage was carried out in
      6 cases, 9 patients received surgical treatment once (3) or twice (6). Two
      patients, operated on while in a coma (stage IV of Bannister scale) died and one
      patient survived with severe disability (operated at stage III). The others (14)
      made a good recovery (6 in grade A and 8 in grade B of Mauser). These results
      were compared with those in the literature and we concluded that the mean factor
      of prognosis is the level of consciousness at the time of initial treatment. In
      most of the cases, burr holes or a small craniotomy, carried out on the basis of
      CT or MRI data, are the easiest and most effective method of surgical treatment.

PMID- 8524445
TI  - [Adequate dialysis revisited].

PMID- 8524446
TI  - [Primary hyperoxaluria].
AB  - Primary hyperoxalurias are inborn errors of metabolism with recessive autosomal
      transmission. Type 1 is due to the deficiency of the hepatic-specific peroxisomal
      enzyme alanine: glyoxylate aminotransferase, and type 2 to that of the glyoxylate
      reductase/D-glycerate dehydrogenase, present in the cytosol of hepatocytes and
      leucocytes. Type 3 is due to increased intestinal absorption of oxalate of
      unknown pathophysiology. In the 3 types, increased oxalate load may lead to
      systemic oxalosis when glomerular filtration rate decreases below 30 ml/min/1.73
      m2, calcium oxalate saturation occurring in plasma when oxalate level
      approximates 50 mumol/l. High fluid intake and long-term co-administration of
      pyridoxine and orthophosphate could perhaps efficiently prevent renal failure in
      a majority of patients. However, combined liver-kidney transplantation presently
      constitutes the most adequate therapy of end-stage renal failure in type 1 and
      perhaps in type 2 hyperoxaluria.

PMID- 8524447
TI  - [Tools for determining adequateness and dialysis dose in peritoneal dialysis].

PMID- 8524448
TI  - [Methodology and practical use in hemodialysis of the percentage of urea
      reduction (PUR)].
AB  - The determination of the perdialytic urea reduction ratio (URR) allows the
      quantification of the dialysis dosage actually delivered to patients. We studied
      the influence of the timing of the post-dialysis blood sampling on the URR, the
      reproducibility of URR and the practical steps to be taken to improve our
      patients' URR. URR (n = 31) is higher when blood sampling is performed before
      (62.4 +/- 4%) than after restitution of the blood circuit, either at the arterial
      (61 +/- 4.2%, p < .0001) or venous needle (60.7 +/- 4.2%, p < .50). Once blood
      sampling modalities are standardized in clinically stable patients with unchanged
      dialysis technique, URR proves highly reproducible (variation coefficient 2.4 +/-
      1.2% of URR). To improve URR in 29 patients, blood flow (n = 20) and/or dialyzer
      surface (n = 14) were increased. In 3 patients HD session duration was increased.
      Altogether, the mean URR in these 29 patients rises from 57.1 +/- 3.8% to 63.4 +/
      4.3% (p < .0001). In conclusion, URR is influenced by the modalities of post
      dialysis blood sampling. URR is reproducible in clinically stable patients with
      unchanged dialysis technique. URR was significantly improved in our patients by
      adaptations of HD technique (mainly blood flow and dialyzer surface).

PMID- 8524449
TI  - [Scintigraphy of iodine 123 labelled serum amyloid P component in beta 2
      microglobulin amyloidosis of hemodialysis].
AB  - To assess the iodine-123-labelled serum amyloid P component (SAP) scintigraphy in
      patients with haemodialysis-associated amyloidosis. PATIENTS: Eight patients with
      histologically proven beta 2-microglobulin amyloidosis. METHODS: Purified SAP was
      iodinated by a modified iodogen method. Whole body data were acquired with a
      large rectangular field gamma-camera. RESULTS: In 7 cases, articular uptake was
      observed in the symptomatic joints (shoulders, wrists, knees) or in view of bone
      cysts (wrists). Among the 3 patients with erosive arthropathy of the hands, only
      one had positive scintigraphy. None positive scintigraphic image was obtained in
      the spine or the hip joint. In one patient with multifocal amyloid joint disease,
      no positive image was noted. No abnormal visceral uptake was observed and
      particularly of the spleen except in one patient with liver uptake. CONCLUSION: I
      123 SAP scintigraphy might be not very sensitive in diagnosing beta 2 amyloid
      deposits. This method needs further investigations and particularly in patients
      undergoing haemodialysis for more than 20 years.

PMID- 8524450
TI  - [Necrotic angiodermatitis revealing a secondary hyperparathyroidism due to
      chronic renal insufficiency: healing after subtotal parathyroidectomy].
AB  - Severe skin necrosis of poor prognosis have been rarely reported among chronic
      renal failure patients. Their clinical outbreak must rapidly lead to search for a
      secondary hyperparathyroidism. Early parathyroidectomy seems is the only
      treatment able to stop the progression of the skin lesions. From an original
      clinical observation we discuss the different mechanisms involved.

PMID- 8524451
TI  - Evidence for a global scanpath strategy in viewing abstract compared with
      realistic images.
AB  - Scanpaths, the repetitive sequences of saccadic eye movements, occurred when
      subjects viewed slide projections of both realistic and abstract art. Variance
      analysis demonstrated that global/local eye movement indices were lower for local
      scanning by professional art viewers who relied on more global viewing,
      particularly in abstract images. Non-professional, unsophisticated subjects
      carried their local scanpath patterns from realistic images on to abstract
      images. The blink rate of professional subjects viewing abstract images was also
      significantly lower, indicating increased visual effort. Non-professional viewers
      showed no difference in blink rates.

PMID- 8524452
TI  - Physiological activation of a cortical network during performance of the
      Wisconsin Card Sorting Test: a positron emission tomography study.
AB  - To determine the neural circuitry engaged by performance of the Wisconsin Card
      Sorting Test (WCST), a neuropsychological test traditionally considered to be
      sensitive to prefrontal lesions, regional cerebral blood flow was measured with
      oxygen-15 water and positron emission tomography (PET) while young normal
      subjects performed the test as well as while they performed a specially designed
      sensorimotor control task. To consider which of the various cognitive operations
      and other experiential phenomena involved in the WCST PET scan are critical for
      the pattern of physiological activation and to focus on the working memory
      component of the test, repeat WCST scans were also performed on nine of the
      subjects after instruction on the test and practice to criteria. We confirmed
      that performance of the WCST engages the frontal cortex and also produces
      activation of a complex network of regions consistently including the inferior
      parietal lobule but also involving the visual association and inferior temporal
      cortices as well as portions of the cerebellum. The WCST activation in the
      dorsolateral prefrontal cortex (DLPFC) remained significant even after training
      and practice on the test, suggesting that working memory may be largely
      responsible for the physiological response in DLPFC during the WCST and,
      conversely, that the DLPFC plays a major role in modulating working memory.

PMID- 8524453
TI  - Increased corpus callosum size in musicians.
AB  - Using in-vivo magnetic resonance morphometry it was investigated whether the
      midsagittal area of the corpus callosum (CC) would differ between 30 professional
      musicians and 30 age-, sex- and handedness-matched controls. Our analyses
      revealed that the anterior half of the CC was significantly larger in musicians.
      This difference was due to the larger anterior CC in the subgroup of musicians
      who had begun musical training before the age of 7. Since anatomic studies have
      provided evidence for a positive correlation between midsagittal callosal size
      and the number of fibers crossing through the CC, these data indicate a
      difference in interhemispheric communication and possibly in hemispheric
      (a)symmetry of sensorimotor areas. Our results are also compatible with plastic
      changes of components of the CC during a maturation period within the first
      decade of human life, similar to those observed in animal studies.

PMID- 8524454
TI  - Corpus callosum and simple visuomotor integration.
AB  - Malcolm Jeeves was the first to demonstrate lengthened interhemispheric
      transmission times in subjects with agenesis of the corpus callosum by using a
      simple reaction time paradigm with lateralized unstructured light stimuli and
      crossed and uncrossed hand responses. Uncrossed responses can be integrated
      within one hemisphere, whereas crossed responses require a communication between
      the two hemispheres. In the normal brain this communication is effected rapidly
      by the corpus callosum, whereas in the acallosal brain it must occur much more
      slowly by way of less efficient alternative interhemispheric pathways. Using a
      similar experimental paradigm we have studied normal subjects, subjects with a
      complete callosal agenesis and epileptic patients with surgical callosal
      sections, either complete or partial. All subjects with complete callosal defects
      showed much lengthened interhemispheric times compared to normal controls.
      Virtually normal interhemispheric transmission times were found in subjects with
      partial callosal defects, whether anterior or posterior, suggesting a possible
      equipotentiality of different portions of the corpus callosum in the mediation of
      crossed manual responses. In both normals and acallosals there were no crossed
      uncrossed differences in reaction time when responses were made unilaterally with
      lower limb effectors or para-axial upper limb effectors, as well as bilaterally
      with upper-limb proximal and para-axial effectors. Since these effectors can be
      controlled directly from either side of the brain via bilaterally distributed
      motor pathways, crossed responses using them, unlike crossed manual responses, do
      not require an interhemispheric integration.

PMID- 8524455
TI  - Visual integration in the split brain.
AB  - A review of evidence suggests that subjects with forebrain commissurotomy can
      integrate information about location, orientation, and movement between visual
      hemifields, albeit with some loss of spatial and temporal resolution, even when
      it is flashed briefly in parafoveal vision. The classic disconnection syndrome
      for visual stimuli is largely explained by the lack of subcortical transfer of
      information about form. Voluntary location-based ('spotlight') attention is
      integrated interhemispherically in these subjects but object-based attention and
      controlled visual search can function concurrently and independently in the two
      hemispheres. The data support the distinction between two visual systems, each
      with its own perceptual and attentional subsystems: (1) a relatively precise
      cortical system dedicated primarily to the analysis of form and the fine-grained
      exploration of visual scenes; and (2) a 'second' subcortical system dedicated to
      a relatively low-resolution processing of movement and location, including
      'spotlight' attention.

PMID- 8524456
TI  - Cellular aspects of callosal connections and their development.
AB  - Detailed visualization, three-dimensional reconstruction, and quantification of
      individual callosal axons interconnecting the visual areas 17 and 18 of the cat
      was undertaken in order to clarify the structural basis for interhemispheric
      interaction. These studies have generated the notion of macro- vs micro
      organization of callosal connections. The first refers to the global distribution
      of callosal connections in the hemisphere as well as to the pattern of area-to
      area connections. The latter refers to the fine radial and tangential
      distributions of individual callosal axons. A discrete disjunctive, 'columnar'
      pattern of termination of callosal axons, previously unknown for the visual
      areas, was found. The consequence of caliber and distribution of callosal axons
      and their branches on the dynamic properties of interhemispheric interactions
      were analyzed by computer simulations. These studies suggested that callosal
      axons could synchronize activity within and between the hemispheres in ways
      relevant for the 'binding' of perceptual features. These new concepts prompted a
      reexamination of the normal development of callosal connections. The central
      issue is whether intrinsic developmental programs, or else cellular interactions
      open to environmental information specify the morphological substrate of
      interhemispheric interactions. The answer to this question is still incomplete.
      In development, transient, widespread arbors of callosal axons, which could
      provide the basis for plastic changes of callosal connections were found in the
      white matter and the deep cortical layers. On the other hand, growth into the
      cortex and synaptogenesis of callosal axons appear to be highly, topographically
      specific albeit not necessarily independent of visual experience.

PMID- 8524457
TI  - Extent and limits of callosal plasticity: presence of disconnection symptoms in
      callosal agenesis.
AB  - Although earlier studies have emphasized the absence of 'split-brain' symptoms in
      callosal agenesis patients, the notion of an 'asymptomatic' acallosal brain has
      lately been challenged. We report a number of findings that are indicative of an
      interruption of interhemispheric communication and integration in individuals
      lacking the corpus callosum. Several groups of patients with callosal pathology
      (acallosals, patients with commissurotomy or callosotomy, either complete or
      partial) were compared to matched controls. Interhemispheric transfer was tested
      in two different experiments involving pointing to a light source while
      maintaining central fixation. In the first experiment, a learning paradigm was
      used to measure transfer of a motor skill from the trained to the untrained hand.
      In the second experiment, subjects pointed to visual targets at different
      locations on a perimeter. Midline fusion, a recurrent theme when describing
      callosal function, was assessed using tasks which included depth perception with
      binocular and/or monocular cues, two-point discrimination thresholds and sound
      localization in the peri-central and lateral fields. Subjects with callosal
      pathology were impaired on all tasks involving transfer of motor and visuo
      spatial skills and on some of the tasks requiring sensory integration of visual
      and tactile information across the body midline. We conclude that these functions
      require an intact corpus callosum since none of these deficits were seen in
      controls equated for IQ.

PMID- 8524458
TI  - From asps to allegations: biological warfare in history.
AB  - Biological warfare has been waged intermittently for nearly 2,500 years. The
      techniques of delivery and weaponization of biological warfare agents have
      gradually evolved from the catapulting of plague victims to the deliberate use of
      infected clothes, insect vectors, and specialized weapon systems. Despite
      advances in immunotherapy and chemotherapy, the threat of biological warfare is
      increasing, and military health personnel should be acquainted with this area.
      This paper reviews the history, often controversial, of biological warfare from
      the Scythian archers through the Russian offensive program in 1994.

PMID- 8524459
TI  - Injuries and illnesses incurred by an army ranger unit during Operation Just
      Cause.
AB  - Detailed knowledge of anticipated casualties is essential for the medical officer
      preparing to support a mission. To accurately describe the injuries inflicted
      upon the 2/75th Ranger Battalion involved in Operation Just Cause, 471 (75.5%)
      Rangers were personally interviewed. The average Ranger was 23 years old, an E-4
      with 3 years of active duty service, and in a good to excellent fitness category.
      The majority went into battle with little sleep or food. Injuries forced 9.5% out
      of combat, and limited another 9.9%. The overall unit casualty rate was 35%, with
      217 Rangers suffering 281 injuries. Most of the injuries were musculoskeletal
      (sprains) and non-surgical, with 90% occurring during the insertion. The lower
      extremity, particularly the ankle, was the most frequently injured area. It is
      hoped that this study will assist those who are planning to support future,
      similar nighttime parachute operations.

PMID- 8524460
TI  - Initiating an ophthalmic laser program for VA outpatients.
AB  - Administrative and clinical considerations for the establishment of an ophthalmic
      laser program at a VA Outpatient Clinic are discussed. Outcomes of the first 320
      patients treated over a 3-year period of time are presented. The program is
      evaluated from the perspectives of patient care, safety, maintenance, education,
      and economics.

PMID- 8524461
TI  - Managed care at Eisenhower Army Medical Center: an initial experience.
AB  - Managed care is receiving a great deal of attention in the health care industry.
      In today's cost-conscious economic environment, managed care has been developed
      in an attempt to maximize quality of health care while minimizing the cost of
      providing that care. The purposes of this article are to (1) review the
      principles of clinical case management; (2) describe the implementation of
      clinical case management and critical paths at Dwight David Eisenhower Army
      Medical Center; (3) elaborate on successful strategies employed; and (4) address
      difficulties encountered. Finally, the study that is currently underway at the
      facility will be briefly discussed.

PMID- 8524462
TI  - Self-reported elevated blood pressure in army officers with hearing loss and
      gunfire noise exposure.
AB  - The association of noise-induced hearing loss from gunfire noise with the
      occurrence of elevated blood pressure was investigated with screening audiometric
      measurement results and a questionnaire in a randomly selected group of 699 army
      officers. After age correction, hearing was found to be deteriorated (i.e., more
      than 20 dB at all of the measured frequencies) in 352 (50.4%) subjects. Of the
      699 officers, 535 (76.5%) reported normal and 164 (23.5%) reported elevated blood
      pressure. In 122 (17.5%), elevation was permanent and verified by a physician.
      The occurrence of elevated blood pressure showed a highly significant correlation
      with severity of hearing loss (chi-square = 25.4; p < 0.001), but not with
      exposure to gunfire noise. Self-reported hypertension seemed to be associated
      with severity of impulse noise-induced hearing loss, but not with the amount of
      gunfire noise exposure. Thus, the present study does not support the suggestion
      that there exists a simultaneous correlation between impulse noise exposure,
      noise-induced hearing loss, and self-reported elevated blood pressure.

PMID- 8524463
TI  - Medical department operations in a fleet hospital during Operation Desert Storm.
AB  - Fleet hospital 15 was deployed to Saudi Arabia in Operation Desert Storm. The
      facility was a 500-bed echelon-3 hospital located near Al Jubail, which served
      the fleet marines from February to April 1991. The medical staff of the
      department of medicine consisted of reserve medical officers with a variety of
      backgrounds. The desert environment, concern for endemic diseases, limitations of
      equipment, and the environment of conflict presented challenges to the medical
      department that required adaptation of civilian skills to this new environment.
      The hospital served as a community medical center, with 86% of the inpatient and
      outpatient treatment provided for non-battle-related illness and injury. Design
      considerations of fleet hospitals for future deployments should include the
      likelihood of treating a large number of non-battle-related injuries and
      illnesses.

PMID- 8524464
TI  - Venous injuries: military versus civilian experience.
AB  - The acute management of venous injuries remains a controversial topic among
      practicing surgeons. A literature review encompassing the last half century was
      performed to clarify the different philosophies proposed in the operative
      treatment of venous injuries. From a military perspective, the Vietnam Vascular
      Registry provided the largest single military experience and follow-up of venous
      injuries to date. The data presented support the concept of the importance of
      venous repair in attempts at limb salvage when faced with a high-velocity missile
      wound. The civilian experience (1960-1992) supports the notion that venous
      ligation in particular circumstances results in little, if any, added morbidity
      to the patient and may be life-saving in certain instances. The two basic
      viewpoints are reviewed with regard to pertinent literature and conclusions drawn
      from these data.

PMID- 8524465
TI  - Use of intravenous sedation for wisdom tooth surgery on aircraft carriers.

PMID- 8524466
TI  - Certified nurse midwives: over twenty years of military service.
AB  - The Department of Defense has utilized certified nurse midwives (CNMs) for the
      delivery of primary women's health care for over 20 years. Although their numbers
      remain relatively small, their impact on quality, cost, choice, and access to
      care is substantial. CNMs are not merely physician extenders, but primary health
      providers who emphasize holistic and wellness-oriented care. This philosophy,
      based on both nursing and midwifery models of care, distinguishes as well as
      makes the CNMs' practice complementary to that of their medical contemporaries.
      This paper presents an overview of what CNMs are, their training, their
      philosophy of care, where they work, and some of the contributions they have made
      to the military health care system.

PMID- 8524467
TI  - Military shoplifting.
AB  - Shoplifting is a crime generally attributed to women. This article describes a
      population of mostly male active duty military shoplifters. Several cases are
      presented and discussed in detail. Shoplifting, and the psychiatric theories
      explaining the behavior, are placed in perspective with a literature review. The
      significance of shoplifting in the military is discussed by examining the law,
      appellate opinions, and the range of punishments. The article concludes by
      providing suggestions for conducting a medico-legal evaluation.

PMID- 8524468
TI  - Medical corps support to a brigade action during an offensive action including
      river crossing.
AB  - This paper describes medical support to a Croatian Army brigade of 2,100 soldiers
      in an attack combined with river crossing during the 1991/1992 war in Croatia.
      Three crossings across the river, 4,000 to 5,000 m apart, were used along a front
      of a total width of 14 km. The anticipated depth of the attack was about 4 km. It
      was estimated that the enemy had about 1,000 fortified soldiers supported by a
      corresponding number of artillery and other weapons. The medical corps were
      strengthened for this particular action by manpower and boats, and the soldiers
      by additional medical accessories (bandages and triangular slings). During the
      action, 78 Croatian Army soldiers were wounded, 7 were killed, and 8 were
      missing. The condition of the wounded soldiers did not worsen during transport.
      The mean duration of the transport was 90 minutes (maximum 2 hours). Twenty-six
      percent of the wounded were definitively treated by the brigade medical corps.
      One physician was included among the seriously wounded. The enemy had more than
      150 dead and about 300 wounded. Upon achievement of the planned objectives, the
      action was interrupted by a high command decision and the brigade returned to its
      initial position.

PMID- 8524469
TI  - Formation and organization of military medical service at the east Slavonia front
      in the 1991/1992 war in Croatia.
AB  - The work of the Croatian Army medical service of the Osijek Military District
      between July 1, 1991, and September 1, 1993, was analyzed. In the former
      Yugoslavia, Croatia was not allowed to have its own army. Therefore, the national
      armed force and medical corps had to be formed during the war against Croatia.
      Medical support to army units was initially provided by civilian medical
      services, i.e., by mobile surgical teams performing their tasks on the model of
      civilian ambulance services. Numerous objective obstacles, such as the lack of
      equipment, qualified military medical professionals, and experience in the
      organization and functioning of army medical corps, were encountered. Seventy
      five members of the Osijek Military District medical service were killed,
      wounded, or missing. There were 145,410 recorded and treated cases of various
      diseases, 21,767 (14.6%) of them referring to war wounds. Forty-three medical
      vehicles were demolished and 20 were damaged. At present, transformation of the
      Croatian Army to a peacetime organization is under way.

PMID- 8524470
TI  - Microparticle immunoenzymatic assay for detection of prostate specific antigen:
      characterization of the technique and comparative analysis with a monoclonal
      immunoradiometric assay.
AB  - Microparticle immunoenzymatic assay (MEIA) is a new, ultrasensitive technique
      recently introduced for detection of prostatic specific antigen (PSA). It is
      easily performed, totally automated, and cheaper and faster than
      radioimmunometric techniques. In this study, the levels of PSA in 194 males with
      urologic problems and healthy males, recorded by microparticle monoclonal
      ultrasensitive enzymoimmunoassay (MEIA) and immunoradiometric assay (IRMA), are
      comparatively evaluated. Variables recorded were age of patient, size and weight
      of the prostate, and PSA levels analyzed by the MEIA (MEIA-PSA) and IRMA (ELSA
      PSA) techniques. Different determinations of PSA were performed in order to
      calculate the intra- and interassay variation coefficient for the MEIA-PSA assay.
      Means of prostatic length, width, and depth, recorded by ultrasonography, were
      28.3, 35.8, and 31.4 mm, respectively, with a mean prostatic size of 19 ml and a
      mean prostatic weight of 23.9 g. Mean IRMA-PSA was 4.53 ng/ml and mean MEIA-PSA
      was 2.04 ng/ml. The difference between them was 2.49, and the ratio IRMA-PSA:MEIA
      PSA was 3.17. Interassay and intraassay variation coefficients for MEIA-PSA were
      6.58 and 9.96%, respectively. MEIA-PSA values correlated linearly with the age of
      the patients (r = 0.65, p = 0.0001), size of the prostate (r = 0.71, p = 0.0001),
      weight of the prostate (r = 0.71, p = 0.0001), and the value of IRMA-PSA (r =
      0.80, p = 0.0001). Paired t tests showed that the values of PSA measured by MEIA
      and IRMA are statistically different (p = 0.0001), with independence of the level
      of PSA considered.

PMID- 8524471
TI  - From mouth to hand: applying dental technology to hand rehabilitation.
AB  - Low-temperature thermoplastic and plaster splints are frequently used in the
      treatment of tendon and ligament injuries of the fingers. Splints made from these
      materials are problematic in that they degrade with exposure to the chemicals and
      physical stresses found in the field environment. Chromium-based alloys, commonly
      used in dental appliances, have been found suitable for use in the fabrication of
      finger splints. Splints made from these materials are lightweight, durable,
      relatively inexpensive, and can withstand the rigors of the field environment.
      Durable splints can enhance clinical outcome and decrease soldier "down time"
      from repeated sick call visits for splint repair.

PMID- 8524472
TI  - Aortic transection secondary to rodeo injury.
AB  - Aortic transection usually occurs in the course of automobile accidents. The
      authors present an unusual case of aortic transection in a 27-year-old male who
      was thrown from a bull during a rodeo competition. Surgical repair was
      successful. The mechanisms of sudden deceleration and blunt impact in the
      pathogenesis of aortic rupture are discussed. A high index of suspicion aids in
      the diagnosis of unusual or subtle cases. Plain chest films may suggest the
      diagnosis, but aortography is currently the gold standard for establishing the
      diagnosis. Surgical repair is mandatory, and the use of left atrial-to-femoral
      bypass may lower the incidence of complications such as paraplegia and renal
      failure. Newer issues in the diagnosis and management of aortic transection
      include the use of transesophageal echocardiography and the placement of
      endoluminal prostheses.

PMID- 8524473
TI  - Marseille nephrology joint meeting 1994.

PMID- 8524474
TI  - Microalbuminuria as a marker of cardiovascular and renal disease in essential
      hypertension.

PMID- 8524475
TI  - Evolution of the characteristics of transplant donors in Spain.
AB  - During the last 4 years the organ donor rate increased in Spain, from 14.3 donors
      per million population per year in 1989 to 22.6 in 1994. This could have been
      even greater, since we observed 25% of family refusal rate during this period.
      The average age of organ donors increased by 4 years during the last 2 years. At
      the same time a change in the cause was mainly cranial trauma, during the last
      year 46% of organ donors died due to cerebrovascular problems, and 45% due to
      trauma, including road traffic and other causes. Road accidents causing death
      have decreased by more than 20% since 1992 explaining such a change in donors
      characteristics. While the percentage positive for hepatitis B virus in the donor
      population has remained stable during last years (1.7%), the percentage of
      (hepatitis C virus-positive donors) increased from 1.7% to 2.7%. Six per cent of
      kidneys grafted in Spain during 1993 were obtained from donors with previous
      hypertensive problems. Current donors are older, more have concomitant problems,
      and most of them died due to cerebrovascular problems; thus we have to be very
      careful about possible influences of these factors on graft outcome, paying great
      attention to donor and organ maintenance, ischaemia times, the use of nephrotoxic
      drugs, etc. Such caution should be increased when considering organs at the limit
      of acceptance for transplantation.

PMID- 8524476
TI  - Cadaveric renal transplantation in patients 60 years of age and older: experience
      with 58 patients in a single centre.

PMID- 8524477
TI  - Five years' experience at one centre with protein A immunoadsorption in patients
      with deleterious allo/autoantibodies (anti-HLA antibodies, autoimmune bleeding
      disorders) and post-transplant patients relapsing with focal glomerular
      sclerosis.
AB  - Protein A is extracted from a strain of Staphylococcus aureus and binds
      specifically to the constant domains of immunoglobulins and possibly to
      fibronectin. It has already been shown that concentrations of all IgG isotypes
      (except IgG3) are efficiently decreased by immunoadsorption (IA) on protein A
      linked to sepharose beads. This system has been developed by Cobe-Excorim Co. to
      either remove IgG in some instances where they wil be harmful, i.e. allo- and
      autoantibodies inducing pathological conditions (autoimmune diseases,
      haematological disorders with allo/autoantibodies, anti-HLA antibodies in
      sensitized patients awaiting organ transplantation) or treat several
      immunological diseases with unknown pathogenesis. In our unit, 20 patients with
      high titres of anti-HLA panel-reactive antibodies, four patients with
      haematological disorders (haemophilia with anti-VIII antibodies and Glanzmann
      diseases) and three patients with post-transplant focal glomerular sclerosis
      (FGS) underwent IA over the past 5 years. Infectious complications were not
      observed after IA and the procedure was always well tolerated. In spite of the
      use of adjunctive immunosuppressive therapy with prednisone and cyclophosphamide,
      and although the reduction in serum IgG was close to 90%, the de novo synthesis
      of allo- and autoantibodies was important after IA procedures. In the cases of
      removal of anti-HLA antibodies, patients with a pre-IA antibody titre which was >
      1:128 clearly did not benefit from the technique and other immunological criteria
      were not predictive of efficacy. Fourteen patients were transplanted, four with a
      well-matched kidney with both pre- and post-IA negative cross-matching, and 10
      with a positive historical cross-match with the donor.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8524478
TI  - Evolution of bone mineral density after renal transplantation: related factors.

PMID- 8524479
TI  - Erythropoietin and erythropoiesis in renal transplantation.
AB  - This report reviews the features of erythropoietin (Epo) production after renal
      transplantation. Successful kidney transplantation leads to the correction of
      renal anaemia over an 8-10 week period. An early ineffective peak of serum Epo
      may occur when there is delayed graft function. A late peak follows the decrease
      in serum creatinine and this is associated with a rise in haemoglobin. Serum Epo
      returns to normal when the haematocrit reaches 32%. Acute early rejection causes
      a striking reduction in serum Epo and reticulocytosis. In some patients the
      haematocrit continues to increase after complete correction of anaemia, resulting
      in post-transplant erythrocytosis (PTE). PTE generally appears to be an
      idiopathic erythrocytosis independent of Epo secretion. A greater Epo sensitivity
      of erythroid progenitors has been suggested. Theophylline and angiotensin
      converting enzyme inhibitors, which attenuate Epo production, can be used to
      treat PTE. The second part of this report describes the possible impact of human
      recombinant Epo (rHuEpo) on renal transplantation. The avoidance of blood
      transfusion with rHuEpo should eliminate the initiation of anti-HLA sensitization
      in uraemic patients without previous pregnancy and prior allograft. In some but
      not all presensitized patients transfusion withdrawal may reduce the
      sensitization level. There is currently no evidence that the reversing of anaemia
      by rHuEpo in kidney recipients impairs early graft function. Our results suggest
      that treatment with rHuEpo prior to transplantation may prevent the appearance of
      PTE. rHuEPO will reverse anaemia in patients with a failing graft and severe
      anaemia with little risk of accelerating graft failure and adverse events.

PMID- 8524480
TI  - Renal functional reserve in calcium channel blocker-treated hypertensive
      recipients of kidney transplant.
AB  - Renal functional reserve during infusion of an amino acid solution was examined
      in 12 cyclosporin-treated kidney recipients at 1 (T1) and 8 months (T2) after
      transplantation. Patients were retrospectively divided into six normotensive (NT)
      and six hypertensive recipients (HT) maintained on monotherapy with a calcium
      channel blocker. Baseline glomerular filtration rates (GFR) were similar in NT
      and HT at T1 and T2. Renal functional reserve was identical in NT and HT at T1
      (15 +/- 7 vs 18 +/- 13 ml/min/1.73 m2) but significantly greater in HT at T2 (11
      +/- 5 vs 23 +/- 10 ml/min/1.73 m2; P < 0.05). At T2, baseline proximal tubule
      outflow (lithium clearance) was greater in HT (26 +/- 8 vs 16 +/- 3 ml/min/1.73
      m2; P < 0.05), whereas fractional proximal reabsorption was less (54 +/- 11% vs
      67 +/- 5%; P < 0.05). These results indicate that: (i) hypertensive recipients on
      calcium channel blocker therapy do not exhibit permanent glomerular
      hyperfiltration until 8 months after transplantation, and have a reduced proximal
      reabsorption; (ii) measurement of amino acid-stimulated GFR and renal functional
      reserve is a more sensitive method than that of baseline GFR for evaluating renal
      function and the effects of therapy in kidney recipients.

PMID- 8524481
TI  - Cytomegaloviraemia and T cell subpopulations in renal transplant patients.
AB  - We studied 54 consecutive recipients of renal transplants to evaluate their
      immunological responses to cytomegalovirus (CMV) infection. Forty-three (79.6%)
      patients developed CMV infection, and all of them subsequently recovered.
      Fourteen of these infected patients (32.6%) developed viraemia during the
      infectious process, four of whom then manifested the disease. The number of
      lymphocytes and their main subpopulations was normal before the appearance of CMV
      infection. During the infection there was a significant growth (P < 0.001) in the
      CD8+DR+ subset, corresponding to activated T suppressor/cytotoxic lymphocytes,
      whereas the natural killer measured subsets remained within normal limits during
      the whole infectious process. As all viraemic patients recovering from the
      infection developed CD8+DR+ activation, we conclude that this recovery is
      associated with the immunological activation.

PMID- 8524482
TI  - Co-infection by hepatitis B virus and hepatitis C virus in renal transplantation:
      morbidity and mortality in 1098 patients.
AB  - The aim of the study was to analyse the influence of co-infection by hepatitis B
      virus (HBV) and hepatitis C virus (HCV) as compared with HCV infection alone in
      1098 patients who received a kidney transplant between 1 January and 31 December
      1991. At transplantation, the prevalence of anti-HCV antibodies was 21.40%
      (235/1098) while the prevalence of HBV infection was 9.85% (108/1096); 46
      patients were co-infected with HBV and HCV, either 19.70% of HCV-infected
      patients and 42.60% of HBV-infected patients. Liver tests, galactose clearance
      and liver biopsy were compared in the 46 co-infected patients (HCV+HBV+) and in
      the 189 HCV-infected patients (HCV+HBV-). At the time of transplantation,
      cytolysis was present in 31.45% of HCV+HBV- patients (50/159) and in 40% of
      HCV+HBV- patients (16/40); cholestasis was present in 34.18% of HCV+HBV- patients
      (34/158) and 42.11% of HCV+HBV+ patients (16/38). At 6 months the incidence of
      biological abnormalities increased to 37% in HCV+HBV- patients (55/150) and to
      52.5% in HCV+HBV+ patients (21/40), suggesting a more deleterious effect of the
      immunosuppressive therapy in the co-infected group. Over the course of
      transplantation, chronic hepatitis was present in 50% of HCV+HBV- patients and in
      64.1% of HCV+HBV+ patients. Liver failure occurred in 7% of HCV+HBV- patients
      (12/156) and 17% of HCV+HBV+ patients (7/41). Galactose clearance was performed
      as a functional test in 68 patients: it was not significantly different in either
      group. Liver biopsy was performed in 108 patients at least once.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8524483
TI  - Hepatitis C and renal transplantation: outcome of patients.

PMID- 8524484
TI  - Combined liver and kidney transplantation in patients with chronic nephritis
      associated with end-stage liver disease.
AB  - A variety of renal diseases can be associated with end-stage liver diseases
      requiring orthotopic liver transplantation (OLT), including cirrhosis-associated
      glomerulonephritis (GN), and nephropathy unrelated to the liver disease. A
      retrospective survey showed that nine patients undergoing liver transplantation
      in our centre had histologically proven GN or interstitial nephritis with renal
      failure and/or nephrotic-range proteinuria, and experienced severe complications
      post-OLT since nephrotoxic immunosuppressive drugs (CsA and FK506) could not be
      adequately given. Four of the nine patients died. Therefore, combined liver
      kidney transplantation has been suggested as first choice treatment in such
      patients. From January 1990 to February 1994, in patients with end-stage liver
      disease referred for OLT, and who presented with unexplained renal function
      impairment and/or significant proteinuria, severe nephropathy was confirmed by
      renal biopsy in nine: four mesangiocapillary GN with immune deposits, one
      membranous nephropathy, two diabetic glomerulosclerosis and two interstitial
      nephritis. All underwent liver transplantation immediately followed by kidney
      transplantation. The postoperative period was uneventful, and neither death nor
      renal failure were recorded. Combined transplantation resulted in all patients in
      the normalization of renal function, and in the disappearance of proteinuria
      within the first postoperative month. From 6 months to 4 years post-transplant,
      the renal function remained within normal ranges in all patients. Routine renal
      transplant biopsy was performed in two patients with pre-transplant cirrhosis
      associated GN, and showed no evidence of recurrence of the original nephropathy.
      We conclude that combined liver-kidney transplantation is an adequate therapeutic
      option in patients with end-stage liver disease associated with advanced kidney
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524485
TI  - The future and the prospective development of renal transplantation.

PMID- 8524486
TI  - Hypertension as a factor in chronic renal insufficiency progression in polycystic
      kidney disease. The Northern Italian Cooperative Study Group.
AB  - The aim of this study was to evaluate the role of blood pressure in the
      progression of chronic renal failure (CRF) in polycystic kidney disease, by
      analysing the behaviour of 74 affected patients, out of 456 CRF patients with
      various underlying nephropathies enrolled in a multicentre, formal prospective
      trial aimed at clarifying the role of protein restriction in retarding CRF
      progression. Because no difference was found between the patients on a low
      protein and those on a controlled protein diet, an inductive analysis was made by
      separating all of the patients into fast progressive or slowly progressive CRF
      groups. Hypertensive patients were defined as those with a mean resting blood
      pressure of more than 107 mmHg; of the 62 polycystic patients who completed the
      study or who reached an end point, 41 patients were hypertensive and 21
      normotensive (10 of whom were pharmacologically controlled). The results of the
      stratified analysis, taking into account the degree of renal function
      deterioration and the underlying disease, showed a significant relationship
      between hypertension and CRF progression only in patients with polycystic kidney
      disease.

PMID- 8524487
TI  - Long- versus short-term effects of two different ACE inhibitors on renal
      haemodynamics: preliminary results from an ongoing trial.

PMID- 8524488
TI  - Can we accurately diagnose nephrosclerosis?

PMID- 8524489
TI  - Calcium channel blockers and renal dysfunction in arterial hypertension.
AB  - Beside effective systemic blood pressure control, calcium channel blockers exert
      several effects on glomerular haemodynamics (namely, preglomerular vasodilatation
      at the early stage of the hypertensive process) and on cellular mechanisms of
      glomerular sclerosis (namely, inhibition of mesangial mechanisms of growth) that
      may provide a renal protective effect in patients with essential hypertension
      and, in turn, may prevent or attenuate the development of nephrosclerosis (Table
      3). However, up to now, there have been relatively few attempts to corroborate
      this assumption in clinical practice. Furthermore, more clinical studies have
      been conducted with the dihydropiridine class of calcium channel blockers. Thus,
      prospective, long-term ongoing studies will help to delineate the long-range
      consequences of the renal actions of the different class of calcium channel
      blockers in essential hypertension.

PMID- 8524490
TI  - Cellular mechanism of resistance to erythropoietin.
AB  - Erythropoiesis is controlled by different regulators. Interleukin 3, granulocyte
      macrophage colony-stimulating factor and stem cell factor play regulatory
      functions in the early steps of erythropoiesis. Erythropoietin (Epo) is the main
      factor which acts positively on the last steps of the production of erythrocytes
      in mammals. Epo is specific for the erythroid progenitor cells and has only
      little effect on other cells. The target cells for Epo are the erythroid
      progenitors (BFUe and CFUe). Epo acts on these progenitors through surface
      receptors specific for Epo. Epo induces the proliferation and differentiation of
      erythroid progenitors leading finally to reticulocytes. During this process,
      certain conditions are required to permit this differentiation: progenitors must
      be present in sufficient numbers, the bone marrow environment must be normal, and
      nutrients such as folic acid, vitamin B12 and particularly iron must be
      available. Elemental iron is an absolute requirement for adequate haemoglobin
      formation. Indeed, in a normal adult, without any stimulation, the bone marrow
      synthesizes 4 x 10(14) molecules of haemoglobin per second, each molecule
      containing four atoms of iron, which roughly corresponds to 20 mg iron. On the
      other hand, erythropoiesis is negatively regulated by several cytokines. These
      are macrophage-derived cytokines, including tumour necrosis factor-alpha (TNF
      alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and transforming growth factor
      beta (TGF-beta). All these factors are elevated in the inflammatory state and are
      implicated in the pathogenesis of anaemia of chronic disease. TNF-alpha has an
      inhibitory effect on erythroid progenitors either directly or mediated by
      interferon-beta (INF-beta). IL-1 inhibits erythropoiesis in vivo in mice and in
      vitro in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524491
TI  - rHuEpo before dialysis and in dialysed patients.

PMID- 8524492
TI  - Subcutaneous erythropoietin administration in predialysis patients: a single
      centre prospective study.
AB  - Since 1991 we have used subcutaneous administration of recombinant human
      erythropoietin (rHuEpo) in predialysis patients selected on the basis of chronic
      anaemia [haemoglobin (Hb) < 7.5 g%] without any extrarenal cause and chronic
      renal failure with a creatinine clearance of less than 10 ml/min. rHuEpo was
      given to 16 predialysis patients with nephropathy, due to chronic
      glomerulonephritis in all 12 of the cases. The sex ratio was 1:1 and mean age was
      65 +/- 9 years (range 43-87). Hb was 7 +/- 0.4 g%. rHuEpo was injected
      subcutaneously thrice weekly while iron was given orally systematically before
      rHuEpo administration. Follow-up was performed monthly until dialysis (mean 9
      months). Anaemia was corrected in all cases (Hb 11 +/- 0.5 g%). Mean Epo dose was
      53 +/- 26 IU/kg/week in males and 47 +/- 11 IU/kg/week in females. Iron was
      systematically added (Fe2+ 8.2 mg/kg/week). Every patient had improved physical
      and intellectual ability after rHuEpo within the first month. No adverse side
      effects were noted but all patients were under antihypertensive therapy (one to
      three drugs). Serum potassium was unchanged. Mean creatinine before treatment was
      507 mumol/l, and was 820 mumol/l after the treatment. Progression of renal
      failure was only affected by rHuEpo in one patient. In this case renal failure
      progression decreased. There was no significant alteration in the slope of the
      creatinine curve from 12 months before to after rHuEpo. Ten patients underwent
      dialysis (five CAPD, five haemodialysis), while six remained dialysis free. From
      January 1991 to December 1993 rHuEpo was given to 12.3% of the end-stage renal
      failure patients on dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524493
TI  - Subcutaneous versus intravenous administration of erythropoietin improves its
      efficiency for the treatment of anaemia in haemodialysis patients.
AB  - Recombinant human erythropoietin (rHuEpo) seems to be more efficient when given
      subcutaneously (SC) instead of intravenously (IV) for therapy of anaemia in
      haemodialysis patients. This was a cross-over study designed to assess the
      efficiency of rHuEpo when given SC rather than IV in a 1 year follow-up. Sixteen
      patients received IV rHuEpo for 6 months, then SC rHuEpo for 6 months. They were
      four males and 12 females with a mean age of 56 years (range 15-82). Haemoglobin
      concentration ([Hb]) was kept at 10 g/dl and transferrin saturation (TS) at more
      than 25%. Mean [Hb] was 9.7 +/- 1.0 g/dl with IV rHuEpo and 9.9 +/- 0.9 g/dl with
      SC rHuEpo (NS). Transferrin saturation was 27% before rHuEpo, 31% with IV rHuEpo
      and 34% with SC rHuEpo (NS vs IV rHuEpo). Serum ferritin was 691 +/- 113 ng/ml
      before rHuEpo, 652 +/- 94 ng/ml with IV rHuEpo and 997 +/- 132 ng/ml with SC
      rHuEpo (P < 0.05 vs IV rHuEpo). Intact parathyroid hormone was 354 +/- 83 pg/ml
      before rHuEpo, 201 +/- 63 pg/ml with IV rHuEpo and 122 +/- 33 pg/ml with SC
      rHuEpo (NS vs IV rHuEpo). Doses of IV rHuEpo were 156 +/- 24 U/kg/week and SC
      rHuEpo 74 +/- 13 U/kg/week (i.e. a saving of 53%; P < 0.001). We conclude that
      subcutaneous administration of rHuEpo is twice as efficient as IV rHuEpo in
      patients with good functional iron reserve.

PMID- 8524494
TI  - Resistance to erythropoietin in iron-overloaded haemodialysis patients can be
      overcome by ascorbic acid administration.
AB  - Haemodialysis patients with iron overload sometimes develop resistance to
      erythropoietin therapy due to 'functional iron deficiency'. It is known that this
      resistance may be overcome by iron supplementation; however, the latter could
      worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis
      patients who had developed relative resistance to erythropoietin (among whom
      three had features of 'functional iron deficiency') with ascorbic acid (500 mg
      intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses
      were voluntarily kept unchanged during the study. After a latency of 2-4 weeks,
      haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7
      +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P <
      0.001). While serum ferritin remained unchanged, transferrin saturation increased
      from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid
      supplementation had allowed mobilization of iron from tissue burdens. In one
      patient, haematocrit declined after withdrawal of vitamin C and increased again
      after rechallenge. Also, ascorbate supplementation was continued after the study
      in two patients and allowed the erythropoietin doses to be decreased, 8 and 11
      weeks, respectively, after the start of the trial. When a control group of seven
      patients with normal iron status and without resistance to erythropoietin were
      challenged in the same manner with ascorbate, no elevation of haematocrit or
      transferrin saturation was noted. We conclude that ascorbate supplementation may
      circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded
      patients, in particular, in the setting of 'functional iron deficiency'.

PMID- 8524495
TI  - Treatment of anaemia resistant to conventional erythropoietin therapy with
      thymopentin in haemodialysis patients.

PMID- 8524496
TI  - Recombinant human erythropoietin and high flux haemodiafiltration.
AB  - Since 1982, 32 uraemic patients were treated in our institution by high flux
      haemodiafiltration (H-HDF) in order to shorten significantly the dialytic
      treatment session. H-HDF used a high surface area filter (1.4-1.9 m2) with high
      hydraulic permeability (polyacrylonitrile and polysulfone), at high blood flow
      (450 ml/min) and high rates of reinfusion of substitution fluid (22 l/session).
      In this way the dialytic session was shortened to 140 +/- 19 min, maintaining a
      good cardiovascular stability and high dialytic efficiency (Kt/V > 1.1). Human
      recombinant erythropoietin rHuEpo introduced in the therapy of this group in 1987
      has resulted in an improvement of renal anaemia, but also a prolongation of the
      time of dialytic treatment due to a decrease in the efficiency of filters. During
      the period of the study, the treatment time increased from 140 +/- 19 min to 168
      +/- 25 min with a concomitant increase of haematocrit and haemoglobin (from 24%
      to 36% and from 7.9 to 10.5 g/dl, respectively). H-HDF maintains a noticeable
      increase in dialytic efficacy with good cardiovascular stability, but the goal of
      a significant reduction in the time of treatment can no longer be obtained.

PMID- 8524497
TI  - The management of uraemia in the elderly: treatment choices.
AB  - The particularity of geriatric medicine and the lack of information due to the
      fact that geriatric nephrology dates back only 10 years explains why the
      management of chronic uraemia among the elderly presents itself as a succession
      of difficult dilemmas. (1) Should causes of chronic renal failure be
      systematically determined and treated? Risk-benefit assessments of the
      investigations and treatments involved in preventing or slowing down the
      evolution to end-stage renal disease (ESRD) are required to answer this question.
      (2) In cases of ESRD, should dialysis always be considered? The fact that life
      expectancy is limited for the aged does not justify depriving them of treatment.
      Nevertheless, in some borderline situations, conservative treatment may be
      preferable. (3) When should dialysis be started? Currently the mortality before
      the 90th day of dialysis is very high among elderly patients. To improve results
      it is probably necessary to determine appropriate criteria for starting treatment
      before complications occur. (4) What is the best method for the first treatment?
      There is much controversy about the respective advantages of haemodialysis and
      peritoneal dialysis. The choice depends on the individual's medical and social
      conditions. (5) Should dialysis treatment be stopped, and, if so, in this case,
      when? The large acceptance rate of elderly patients for dialysis implies that
      withdrawal of treatment must sometimes be considered. Fears linked to this
      dilemma probably explain why some physicians choose to exclude elderly patients
      from dialysis. It seems to us more ethical to treat this group of patients and
      assume responsibility for stopping treatment should it be necessary.

PMID- 8524498
TI  - Prevalence of micro- and macroalbuminuria and their relationship with other
      cardiovascular risk factors in essential hypertension.
AB  - A cohort of 227 untreated essential hypertensive patients from north-western
      Italy was studied in order to evaluate the prevalence of micro- and
      macroalbuminuria and their relationship with other cardiovascular risk factors.
      Albuminuria was evaluated as the albumin to creatinine ratio (Alb/Cr) in three
      non-consecutive first morning samples. The prevalence of microalbuminuria and
      macroalbuminuria was 10% and 2.2%, respectively. Albuminuric patients showed
      higher blood pressure, serum creatinine, triglycerides and uric acid as well as a
      greater prevalence of retinopathy. Stepwise multiple regression analysis
      demonstrated that only a small part of variations in albuminuria was explained by
      changes in blood pressure. Duration of disease did not seem to influence
      microalbuminuria. The presence of hypertensive retinopathy was associated with
      greater albuminuria, longer duration of hypertension, and higher prevalence of
      major ECG changes, but not with higher blood pressure levels. Microalbuminuria,
      rather than a consequence of elevated blood pressure levels, seems to be a marker
      of a syndrome featuring, among other characteristics, essential hypertension.
      Furthermore, microalbuminuria must be considered as an independent cardiovascular
      risk factor.

PMID- 8524499
TI  - Dialysis in the elderly: improvement of survival results in the eighties.
AB  - Analysis of long-term dialysis results is the cornerstone of renal replacement
      therapy evaluation. Elderly patients may be considered a crucial cohort, since
      subtle differences may be enhanced in a population of lower life expectancy. The
      aim of the study was an analysis, from the Piedmont Registry of Dialysis and
      Transplantation, of the results obtained in 1981-1992 (northern Italy, about
      4,400,000 inhabitants, 21 dialysis centres, open acceptance since mid-1970s) in
      patients aged > or = 65 years (475 patients started treatment in 1981-1985, 1026
      in 1986-1992). As a first treatment, during the 12 years considered acetate
      haemodialysis decreased sharply; bicarbonate haemodialysis is currently the
      standard treatment (68%). Peritoneal dialysis is stable (21%), and
      haemodiafiltration is increasing (8%). Shifts between treatments are frequent:
      15% of elderly patients changed treatment at least once in 1991-1992.
      Nephroangiosclerosis/ischaemic renal disease, undefined causes and diabetes
      mellitus are the major causes of end-stage renal disease; 57.3% of patients have
      high risk conditions in addition to age. In this cohort of patients, mean age of
      new cases starting dialysis significantly increased in 1986-1992 (72.7 +/- 5.4
      years) versus 1981-1985 (71.3 +/- 4.5; P < 0.001). Despite this, survival at 2
      years increased significantly from 54.6% in the period 1981-1985 to 59% in the
      period 1986-1992 (P < 0.05). Even in an ageing dialysis population, therefore,
      choice of an open dialysis system with easy changes among treatments allowed
      improvement of survival results; further technical advances may help in
      maintaining present trends.

PMID- 8524500
TI  - Nutritional status in the elderly patient with uraemia.
AB  - An increasing number of elderly patients with uraemia are treated by dialysis
      therapy. Virtually every published study on nutritional status of patients
      undergoing maintenance haemodialysis treatment or continuous ambulatory
      peritoneal dialysis (CAPD) has indicated that a substantial proportion of
      patients undergoing regular dialysis treatment have protein calorie malnutrition.
      Problems of undernutrition increase significantly with age; a combination of
      socioeconomic, psychological, and biochemical problems interfering with acquiring
      and assimilating a balanced diet are responsible for nutritional deficiencies in
      older people. We assessed the prevalence of protein calorie malnutrition in 183
      regular dialysis patients aged 65 years or older treated with haemodialysis or
      CAPD. This group of patients was compared to two other groups aged 18-40 years
      (62 patients) and 41-64 years (239 patients). Presence of malnutrition was
      assessed by selected serum chemistries, anthropometry and Subjective Global
      Nutritional Assessment. Adequacy of dialysis, protein nitrogen appearance, as an
      index of protein intake, and residual renal function were measured. The results
      indicate that protein calorie malnutrition occurs commonly in regular dialysis
      patients, with a higher prevalence of malnutrition in the elderly; 51% of
      patients of the elderly group were classified as malnourished, and no difference
      was found with the two dialytic modalities.

PMID- 8524501
TI  - Chronic haemodialysis in elderly patients.

PMID- 8524502
TI  - Are serum albumin and cholesterol reliable outcome markers in elderly dialysis
      patients?
AB  - Albumin and cholesterol are considered reliable outcome markers in dialysis
      patients; their influence, however, may also be related to non-independent
      factors, such as age and presence of co-morbid conditions. The aim of the study
      was an analysis of four outcome markers, assessed at start of dialysis: age, high
      risk conditions, cholesterol and albumin levels. Data were obtained from the
      Piedmont Dialysis and Transplantation Registry (northern Italy, about 4,400,000
      inhabitants, 21 dialysis centres, open acceptance since mid-1970s, 5661 patients
      on file at 31 December 1992). Prevalence of albumin and cholesterol in the normal
      range increases with age; in each age group prevalence in the range is higher in
      patients at high risk. However, influence of these biochemical parameters is
      evident also in no-risk cohorts, thus identifying a subgroup with poorer
      prognosis also in the population without any identified classic risk factor. The
      influence of albumin, more evident in the population studied compared with
      cholesterol, is reflected by impaired survival of low-albumin patients (age > or
      = 65 high risk at 1 year: 60.7% vs 76.6%, P = 0.0052; age > or = 65 non-high
      risk, at 1 year: 76.5% vs 90.7%, P = 0.0001). In conclusion, albumin and
      cholesterol, assessed at start of dialysis, are reliable outcome markers even in
      elderly patients, identifying, in this high mortality cohort, a subgroup with
      poorer prognosis. If and how their effect may be reversed by dialysis therapy
      remains to be assessed.

PMID- 8524503
TI  - Prevalence of hepatitis C virus in dialysis patients in Spain. Spanish
      Multicentre Study Group.
AB  - Several studies have reported a high prevalence of hepatitis C virus (HCV)
      antibodies in dialysis patients. In order to determine HCV prevalence in Spain,
      we conducted a nationwide survey of patients on several modalities of dialysis.
      We found a greater HCV antibodies prevalence in dialysis patients than in the
      healthy Spanish population, and higher prevalence in patients on haemodialysis
      than in patients on peritoneal dialysis. In addition, the prevalence of HCV
      antibodies is higher in nurses than in the rest of the dialysis unit staff.

PMID- 8524504
TI  - Epidemiological factors involved in hepatitis C virus infection in patients with
      renal disease.

PMID- 8524505
TI  - Hepatitis C virus infection in haemodialysis patients: lessons from epidemiology
      and prophylaxis.

PMID- 8524506
TI  - Implications of chronic hepatitis B or hepatitis C infection for renal transplant
      candidates.
AB  - Hepatic cirrhosis and clinically active hepatitis due to HBV or HCV infection
      clearly contra-indicate kidney transplantation. More controversial is the
      attitude to be adopted towards candidates with clinically quiescent chronic HBV
      or HCV infection. The presence of the HBs antigen does not adversely affect
      survival or increase morbidity on maintenance haemodialysis, at least during the
      first decade. After transplantation, by contrast, the long-term outcome of HBV
      infection is undoubtedly worse than on haemodialysis: more patients develop
      chronic hepatitis and eventually die from liver disease. The risk of fatal liver
      disease after transplantation is greater in patients with markers of active viral
      replication before transplant and in those with severe histological liver
      lesions. Pretransplant candidates should be warned of this significant risk
      factor. Comparison of survival of HCV-infected patients on haemodialysis and
      after transplantation is not yet possible. The outcome of HCV infection after
      transplantation appears less severe than that of HBV infection: the survival of
      anti-HCV-positive patients is similar to that of anti-HCV-negative patients, at
      least during the first decade after transplantation. Liver biochemical
      abnormalities, serological markers and detection of HCV RNA are of little value
      to identify patients at greater risk of poor outcome after transplantation. Only
      liver biopsy might help identify such patients. Both efficacy and risks of
      antiviral therapies are yet to be properly assessed during haemodialysis.
      Preliminary evidence suggests that interferon therapy given after transplantation
      entails an unacceptable rate of deterioration in graft function.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8524507
TI  - Preliminary results of treatment of chronic hepatitis C with recombinant
      interferon alpha in renal transplant patients.
AB  - Chronic hepatitis C is a common cause of viral liver disease in kidney transplant
      recipients. To assess the efficacy and the safety of therapy with interferon
      alpha (IFN alpha) in such a population we conducted a prospective study where 16
      kidney transplant recipients with chronic hepatitis C received recombinant IFN
      alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All
      the patients had stable renal function for at least 1 year (mean serum creatinine
      125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the
      beginning of the study. In 15 patients serum alanine aminotransferase (ALT)
      levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P =
      0.0044). ALT remained in the normal range as long as IFN alpha was continued.
      Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to
      88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven
      responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end
      of IFN alpha therapy remained positive in all the patients who scored positive at
      the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight
      loss) were frequent leading to four patients dropping out of the study. The
      haematological tolerance was moderate. The major concern was the increase in
      serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only
      six patients experienced renal failure occurring 45-168 days after the beginning
      of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered
      interstitial inflammatory cellular infiltration and moderate mesangial
      hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524508
TI  - Clinical criteria for selecting recipients of renal transplantation.

PMID- 8524509
TI  - Dentists lose state jury exemption. Are solo practitioners doomed?

PMID- 8524510
TI  - Alternative voices.

PMID- 8524511
TI  - Keep an open mind.

PMID- 8524512
TI  - Answers are in the past.

PMID- 8524513
TI  - Fluoride gone.

PMID- 8524514
TI  - New guidelines.

PMID- 8524515
TI  - A managed care primer.

PMID- 8524516
TI  - Is dentistry through with film?
AB  - Film is the top choice for a full-mouth radiographic series. While cost and
      computer dependency are no longer major obstacles to using filmless radiography
      (FR), many clinicians still are reluctant to adopt the newer method because they
      are concerned about its diagnostic efficacy. Those concerns are not borne out in
      recent dental literature. FR's diagnostic capabilities and beneficial properties,
      which include decreased patient radiation exposure and nominal time needed to
      view an X-ray image, may have helped it surpass film as the modality of choice
      for some aspects of dental radiography, particularly procedures requiring
      selective periapical radiographic analysis.

PMID- 8524517
TI  - AGD action defies the English language.

PMID- 8524518
TI  - The role of bioelectronic instruments in the management of TMD.
AB  - Temporomandibular disorders (TMD) comprise a group of conditions that can affect
      the form and function of the temporomandibular joint (TMJ), masticatory muscles
      and dental apparatus. Proper management of TMD by the dentist requires accurate
      appraisal of the status of the patient's dentition, TMJ and associated
      neuromuscular apparatus. Certain predefined standards or parameters of
      function/dysfunction are accepted by the profession. Electronic instrumentation
      provides objective measurement of many of these biological phenomena, and thus
      can be used throughout treatment for critical analyses that monitor and enhance
      treatment efficacy. A treatment protocol for TMD is presented that uses
      electronic instrumentation to establish a neuromuscular occlusion.

PMID- 8524519
TI  - Occlusion as a causative factor in TMD. Scientific basis to occlusal therapy.
AB  - There appears to be a pendulum swing toward large epidemiologic studies
      questioning the role of occlusion in dentistry. This article clearly demonstrates
      that significant scientific evidence exists on the side of occlusal causative
      factors. Clinicians need this current information to base practical decisions of
      treatment relative to both patients and those requiring restorative procedures.
      It further correctly clarifies that stress-related issues have an important role,
      along with other host-susceptibility altering factors.

PMID- 8524520
TI  - Relationship of muscular strength to jaw posture in sports dentistry.
AB  - From the late 1970s until the early 1990s there have been several reports of
      improved appendage muscle strength and athletic performance. Much of the
      criticism of using a mouthguard alone or in conjunction with a splint, such as a
      mandibular orthopedic repositioning appliance (MORA), to enhance athletic
      performance has been aimed at study designs, controls, periods of time, double
      blindness and the placebo effect. Although it would appear that designing a study
      that would please both clinician and researcher would be a difficult task,
      studies have been performed that do meet the "gold standard"; and the results
      favor the premise that jaw repositioning can enhance appendage muscular strength
      and athletic performance. Previous studies performed in the mid-1980s, and to
      which the scientific community refers to continually, on closer examination are
      flawed.

PMID- 8524521
TI  - TMJ arthrocentesis. A conservative surgical alternative.
AB  - TMJ arthrocentesis entails placing two needles into the joint space for purposes
      of lysis and lavage via hydraulic distension. For arthropathy patients
      unresponsive to nonsurgical care, arthrocentesis is a simplified alternative to
      the most common arthroscopic surgical procedure. It is minimally invasive and may
      be performed in the office with comparable success and diminished morbidity.

PMID- 8524522
TI  - The history of dental radiology.
AB  - Several events leading to discovery of the X-ray beam by Wilhelm Conrad Roentgen
      in November 1895 are traced. Some early dental radiologic advances are discussed.

PMID- 8524523
TI  - Monitoring the fetal heart: a continuing controversy.

PMID- 8524524
TI  - Malignant melanoma of the vulva: a review.
AB  - Vulvar melanoma is an unusual tumor with a poor prognosis. Most surgeons have
      abandoned radical vulvectomy as the treatment of choice. The role of elective
      node dissection is controversial. Currently effective adjuvant therapy is
      lacking. In this paper 51 sources concerning melanoma and/or melanoma of the
      vulva were reviewed, 43 of these sources were considered to be pertinent and
      current enough to include in this review. The objective was to describe current
      knowledge about the natural history, staging, pathology, and treatment of
      melanoma of the vulva. It has been found that melanoma continues to be difficult
      to treat when in advanced stages. Microstaging systems offer clinicians the best
      prognostic information. In many patients, less radical surgical treatment offers
      equal cure rates with decreased morbidity.

PMID- 8524525
TI  - Recurrent endometriosis: a review of biological and clinical aspects.
AB  - The recurrence of pelvic endometriosis some time after the initial treatment is a
      common finding in clinical practice. When symptoms of endometriosis reappear
      several months after treatment, it is difficult to distinguish between recurrence
      and persistence of the disease. In this review, the current hypotheses about the
      biological basis of endometriosis recurrence/persistence are discussed. The
      results of several clinical trials estimating the recurrence rate of
      endometriosis after medical, surgical, and combined treatments are presented. In
      addition, a critical analysis of the tools available for the diagnosis of
      recurrent endometriosis is made, and some therapeutic options to treat recurrent
      endometriosis are discussed with recommendations for their use.

PMID- 8524526
TI  - Pemphigus vulgaris and pregnancy.
AB  - Pemphigus vulgaris (PV), an autoimmune bullous dermatosis, is rarely encountered
      in pregnancy. Two women with PV and their three pregnancies are described.
      Pregnancy outcome was generally good, although one of the neonates had
      characteristic PV skin lesions that resolved spontaneously. The pathophysiology,
      clinical manifestations, and special issues of PV pertaining to pregnancy are
      discussed. With our cases added, there are now 23 reports in the English
      literature on PV in pregnancy. From these data it seems that transient skin
      lesions may occasionally appear in the neonate regardless of the severity of
      maternal disease. Such lesions are due to passive transplacental transfer of PV
      antibodies and do not have long-lasting clinical implication. On the other hand,
      and contrary to past traditional thinking, PV may be associated with poor
      neonatal outcome including prematurity and fetal death. Such complications seem
      to be restricted to pregnancies with clinically severe PV.

PMID- 8524527
TI  - Instrumentation in hysteroscopy.
AB  - Good instruments and proper training enable one to make an accurate diagnosis and
      to operate successfully to correct an intrauterine abnormality. There are a
      limited number of instruments for diagnostic and operative hysteroscopy so that
      the gynecologist can quickly become acquainted with the most appropriate
      instruments for each clinical situation.

PMID- 8524528
TI  - Media and delivery systems.
AB  - Distention media are necessary for panoramic and operative hysteroscopy. The
      ability to see the uterine cavity and perform operative procedures under direct
      vision are the major advantages of hysteroscopy. The hysteroscopic surgeons'
      operative capacity is enhanced or restricted by the choice and effective use of
      distending media and their delivery systems.

PMID- 8524529
TI  - Power sources.
AB  - The rapid development of endoscopic surgery has created an ever-increasing demand
      for new instruments, such as lasers of various wavelengths, and new applications
      of high-frequency electrosurgery. The technology has advanced rapidly and it is
      sometimes difficult to understand the different applications of these new
      instruments and take full advantage of these developments. This article has
      reviewed the basic principles of the various power sources commonly utilized in
      gynecologic surgery and described the clinical applications of each of them.

PMID- 8524530
TI  - Contraindications and complications of hysteroscopy.
AB  - If the contraindications to hysteroscopy are observed, complications should be
      small. The risks of fluid overload, especially in operative cases, is the most
      common critical problem, so that accurate recording of fluid use and collection
      are essential. The inexperienced, unsupervised surgeon is most likely to
      encounter significant complications.

PMID- 8524531
TI  - Office hysteroscopy.
AB  - Diagnostic, panoramic hysteroscopy can be performed in an office setting with
      small discomfort to the patient. The procedure enables the physician to search
      for organic intrauterine abnormalities and to select the proper form of therapy
      based on the observations. Often no pathology is seen and further surgical
      interventions are not needed. This operation currently represents the state of
      the art for investigation of the endometrial cavity. In the future it will become
      the standard of care as the first step for evaluation of causes of abnormal
      uterine bleeding in selected patients.

PMID- 8524532
TI  - Hysteroscopic metroplasty for septate uterus.
AB  - Reproductive results in women with a septate uterus include increased incidence
      of spontaneous abortion, premature birth, and abnormal fetal presentations.
      Septate uterus is seen most often in women with reproductive wastage. This
      article discusses the diagnosis, indications for surgery, surgical technique,
      results, and complications for treating patients with a septate uterus.

PMID- 8524533
TI  - Intrauterine adhesions.
AB  - Anticipation and suspicion are critical aspects to any discussion of intrauterine
      adhesions. Curettage between the second and fourth week postpartum is more likely
      to cause adhesions than is any other endometrial trauma. Infertility, recurrent
      abortion, or menstrual aberrations after any uterine trauma should cause the
      physician to suspect the presence of intrauterine adhesions.
      Hysterosalpingography and hysteroscopy are the ideal methods to make the
      diagnosis of IUA, and the latter is the safest, least traumatic, and most precise
      method of treating adhesions. The addition of an intrauterine splint and high
      dose estrogen therapy completes the therapeutic approach. Before attempting
      conception the cavity should be inspected to verify its normality.

PMID- 8524534
TI  - Hysteroscopy and assisted reproductive technology.
AB  - Hysteroscopy is an excellent additional instrument for evaluating the uterine
      characteristics in infertile women. This article reviews the two main indications
      for hysteroscopy in infertile patients who are candidates for assisted
      reproductive techniques: (1) to evaluate the cervix and uterine cavity and (2)
      rule out any pathology or lesions that could have been missed by
      hysterosalpingography. Hysteroscopy has been proposed as an alternative method to
      traditional transabdominal transfer of gamete or embryo to the tube.

PMID- 8524535
TI  - Tubal cannulation.
AB  - While uterotubal chromopertubations were performed early in the 1970s with the
      introduction of hysteroscopy, cornual cannulation was extended and adapted to
      fluoroscopy. The disadvantages of fluoroscopy include the difficulty in ruling
      out tubal spasm, inability to evaluate distal tubal disease, and other pelvic
      abnormalities. Tubal cannulation has emerged as an excellent alternative to treat
      patients with cornual obstruction. Only those patients in whom cannulation fails
      should be subjected to microsurgical reconstruction. While cannulation with
      coaxial catheters began under fluoroscopy, the use of the hysteroscope simplifies
      the technique. With laparoscopy the hysteroscopic approach enables tubal
      cannulation and evaluation of the entire pelvis. Treatment of additional problems
      affecting the fallopian tubes, particularly adhesions and endometriosis, is
      possible. Laparoscopy helps in monitoring the procedure and visual assessment of
      tubal patency. The ability to observe the uterotubal junctions directly by
      hysteroscopy provides an excellent approach for tubal cannulation. There are two
      techniques to cannulate the fallopian tubes, either with coaxial catheters or
      catheters with distal balloons, but the result obtained with these two techniques
      is similar. The simplicity of coaxial catheters makes this approach more
      appealing, and with the hysteroscope one can avoid exposure to radiation. The
      results obtained with tubal cannulation are encouraging and this procedure should
      be offered as the initial method to attempt treatment of tubal cornual
      obstruction. Often it can represent an excellent alternative to microsurgical
      tubal anastomosis, avoiding a laparotomy and extended disability.

PMID- 8524536
TI  - Hysteroscopic submucous myomectomy.
AB  - Symptomatic submucous myomata are now diagnosed and evaluated with hysteroscopy
      in the office or operating room. Excision under hysteroscopic control using a
      resectoscope or other equipment and techniques is described and the long term
      outcome is reported. The hysteroscopic approach to the symptomatic submucous
      myoma has dramatically changed the treatment options for patients who classically
      would be offered abdominal myomectomy or hysterectomy.

PMID- 8524537
TI  - Hysteroscopic endometrial ablation.
AB  - The addition of endometrial ablation to gynecologic surgical procedures has had a
      significant impact on the management of intractable menorrhagia. It is an
      outpatient procedure that causes limited disability to the patient. Although long
      term data regarding this procedure are not available, the laser ablation series
      dates back to 1979 and there have been no delayed sequelae.

PMID- 8524538
TI  - Hysteroscopy and adenocarcinoma.
AB  - Although the diagnostic accuracy of hysteroscopy is high, it should be considered
      a diagnostic technique and used together with endometrial biopsy. Hysteroscopy is
      useful for excluding those patients with abnormal uterine bleeding who show no
      signs of intrauterine pathology. The number of cases in which hysteroscopy is
      sufficient for reaching a diagnosis without the help of a subsequent biopsy will
      depend directly on the experience of the endoscopist. After a fair amount of
      practice, it is possible to use hysteroscopy for the identification of patients
      with either benign or malignant endometrial lesions with about 20% false
      positives and no false negatives. The combined use of hysteroscopy and biopsy
      leads to near 100% accuracy in the diagnosis of endometrial neoplasia and its
      precursors. The combination of hysteroscopy and endometrial biopsy is ideal for
      use in symptomatic patients for the early detection of endometrial neoplasia, its
      precursors, and benign lesions that cause abnormal bleeding. With benign and
      malignant endometrial lesions, the first symptom is generally bleeding. Zampi and
      coworkers analyzed the hysteroscopic finding and menometrorrhagia in 1295 women.
      While cystic hyperplasia and endometrial neoplasia gave rise to bleeding in many
      patients, many other lesions also caused the same symptom. Hysteroscopy
      represents the ideal technique for the examination of women over the age of 45
      who complain of abnormal uterine bleeding. In association with endometrial
      biopsy, it can detect endometrial adenocarcinoma in its early stages and select
      those patients who have precursor lesions.

PMID- 8524539
TI  - Hysteroscopic sterilization.
AB  - Despite the numerous painstaking evaluative trials that were conducted for more
      than two decades, hysteroscopic sterilization techniques remain more of a concept
      than a reality. However, it is likely that transcervical methods will continue to
      attract the investigator who is interested in simple, inexpensive outpatient
      office or female sterilization procedures in the clinic. Regardless, the cost of
      clinical trials, required follow-up, and preclinical toxicologic evaluations may
      continue to inhibit further research in this area.

PMID- 8524540
TI  - Hysteroscopy and hysterography.
AB  - Hysteroscopy and hysterography approach the uterine cavity in different ways and
      each has advantages and limitations. Hysteroscopy is more accurate for the
      diagnosis of abnormalities that project into the uterine cavity such as polyps,
      submucous myomas, endometrial hyperplasia, and endometrial adenocarcinoma.
      Contrast media used in hysterography enable the detection of lesions that
      penetrate the myometrium and congenital and acquired partitions of the uterine
      cavity. Diagnostic hysteroscopy, easily performed as an office procedure, should
      be the screening method of choice to search for uterine abnormalities except for
      the infertility patient who also requires a salpingogram. Hysterography should be
      considered as a complementary procedure only when the direct visual examination
      proves incomplete or inadequate. It is necessary for a thorough assessment of
      uterine malformations, adenomyosis, complex intrauterine adhesions, and uterine
      scars.

PMID- 8524541
TI  - Documentation in endoscopy.
AB  - The use of video monitoring and imaging techniques have enhanced endoscopic
      documentation. Conventional photographic techniques using 35-mm photography
      produce excellent quality images but are cumbersome for routine use. Electronic
      images can be recorded on videotape or printed, and they can be stored
      electronically on computer or disk.

PMID- 8524542
TI  - The future of hysteroscopy.
AB  - Hysteroscopy is rapidly becoming a common examination for every gynecologist. As
      an office procedure, it is one of the most valuable ways to detect intrauterine
      lesions. Benign and malignant changes in the endometrium can be diagnosed at an
      early stage, and problems in the uterine cavity that can cause sterility can be
      recognized and treated.

PMID- 8524543
TI  - [The effect of a serotonin deficiency on mammalian embryonic development].
AB  - Administration of p-chlorophenylalanine to mouse females leading to a decreased
      level of endogenous serotonin during the early periods of pregnancy leads either
      to the absence of cytokinesis at the stage of zygote or to a sharp reduction of
      the cleavage rate in embryos up to its complete arrest. Formation of the
      blastocyst is impaired, although cavitation may take place at the same time as in
      the control. In the latter case, the blastocysts consist of a small number of
      large blastomeres, and the separation into trophoblast and inner cell mass is
      characteristically indistinct. Decreased level of endogenous serotonin at early
      postimplantation stages, i.e., during active organogenesis, leads to
      abnormalities in the development of brain, eyes, jaws, abnormalities of the brain
      vessels and vascular system of other body regions, which appear as numerous
      hematomas and hemostasis in vessels.

PMID- 8524544
TI  - [The role of chloride channels and chlorine ions in regulating the in-vitro
      chorionic gonadotropin-stimulated maturation of oocytes in the clawed toad].
AB  - The blocker of chloride channels SITS (4-acetamido-4'-isothiocyanostilbene-2,2'
      disulphonic acid) (1 and 10 microM) reliable inhibited maturation of Xenopus
      laevis oocytes stimulated in vitro by human chorionic gonadotropin (5-40 MU/ml)
      and decreased the progesterone content of the incubation medium. The effect of
      SITS was dose-dependent and decreased with the increase of the hormone
      concentration. When the chloride ions in the medium were substituted for
      equimolar concentrations of sodium, potassium and calcium glutamates or of sodium
      or potassium chlorides for, respectively, glutamine and aspartate, the percentage
      of definitive oocytes (1.2-1.4 mm), maturing under the influence of human
      chorionic gonadotropin and the progesterone contents of the incubation medium
      increased, the certain part of smaller oocytes (0.9-1 mm).

PMID- 8524545
TI  - [The membrane receptor binding of thyroid hormones in rat liver and brain cells
      in ontogeny].
AB  - We studied changes of phospholipid and fatty acid composition of highly purified
      plasma membranes of liver and brain cells of rats over time during ontogenesis.
      Membranes were isolated from the organs of 2-day-old embryos, 6-day-old newborn
      rats, and adult rats. We examined the binding of thyroxine, a thyroid hormone, by
      preparations of plasma membranes from liver and brain at these times and have
      determined any tissue specificity in the development of membrane-mediated
      thyroxine reception during ontogenesis.

PMID- 8524546
TI  - [The dynamics of the formation of spontaneous autoantibodies to the synaptonemal
      complex in male mice].
AB  - Time-related changes in formation of spontaneous autoantibodies against the
      synaptonemal complex were studied by indirect immunofluorescence in male mice.
      Appearance of the spontaneous autoantibodies against the synaptonemal complex
      coincided with that of the cells containing synaptonemal complexes. The mouse
      synaptonemal complexes were binding spontaneous autoantibodies of the rabbit and
      human sera. The synaptonemal complexes of the equine spermatocytes were binding
      spontaneous autoantibodies of the mouse serum. There was no fluorescence of
      synaptonemal complexes on preparations of spread rye meiocytes treated with the
      mouse serum. Antigenic similarity was shown for the synaptonemal complex
      components in representatives of the different mammalian orders: rodents, odd
      toed ungulates, and primates.

PMID- 8524547
TI  - [The centrosome structure in enterocytes in the histogenesis of the mouse
      intestine].
AB  - We studied characteristics of the centrosome during histogenesis of epithelium of
      the middle region of the mouse embryo gut. We demonstrated that between days 11
      and 13 of embryonic development, the middle gut region is formed by a single
      layer plasmatic epithelium, at day 14 it consists of multi-layer sheet of cuboid
      cells (at this period morphological separation of gut layers takes place), and at
      day 16 the whole mucosa consists of a single layer plasmatic epithelium. At this
      time, matter of membrane of adjacent cells produce tight junctions and never form
      desmosomes. During enterocyte differentiation, the Golgi complex moves from the
      apical part of the cell towards the nucleus and is always spatially uncoupled
      from the centrosome. From day 11 to day 13 of embryonic development, the active
      centriole of the centrosome in the majority of cells of epithelium of the
      intestinal tube represents the basal body of the primary cilium, which is located
      in the apical part of cells and is often directed towards the gut lumen.
      Replication of cells takes place independently of the presence or absence of the
      cilium. From day 13 to day 15 of embryonic development, the number of enterocytes
      possessing the cilium decreases, and in a number of cells the centriole only
      produces a contact with the internal membrane vesicle or with the plasma membrane
      ("stump"). At day 6 of embryonic development, no cells possessing cilium can be
      found. It is proposed that the change in the outer structure of the centrosome
      can serve as an early marker of cell differentiation.

PMID- 8524548
TI  - [Pharmacotherapy of anxiety disorders].
AB  - The pharmacotherapy of anxiety disorders has revolutionary changed in the last
      few years. This ICD-10 based review of the literature provides help for general
      practitioners and other specialists in the short and long term treatment of
      anxiety as well as in the discontinuation of pharmacologic treatment. The author
      describes the use of high potency benzodiazepines, selective serotonin reuptake
      inhibitors and 5 HT1A partial agonists and summarizes the disadvantages of some
      older drugs still in use for the treatment of anxiety disorders.

PMID- 8524549
TI  - [Quality assurance, audit and quality control of radiotherapy at radiology
      departments in Hungary].
AB  - The first quality assurance, audit and control system in the Hungarian "'health"
      care industry" is described for the medical specialty of radiotherapy. The
      prerequisites of the elaboration of the programme were an exact knowledge of the
      current Hungarian infrastructural and staffing conditions, and the
      radiotherapeutic activities. The recommendations cover the 5 medical universities
      including the national institute (the Debrecen, Pecs, Semmelweis, Szent-Gyorgyk
      Albert Medical Universities, and Haynal Imre University of Health Sciences) and
      the 5 regional oncological centres in hospitals (Josa Andras, Markusovszky, Petz
      Aladar, Szentpeteri kapu and Uzsoki Hospitals). The departmental functions
      (patient care, teaching-education, research work and scientific organizing
      activity) and the structure (organization, infrastructure, staffing conditions,
      etc.) are described first, followed by the therapeutic principles and clinical
      process (patient referral and selection, decision-making, priorities in therapy
      initiation, treatment preparation and execution, etc.). The informal daily/weekly
      quality assurance programme long applied in the routine patient care has been
      formalized and supplemented with a weekly audit conference. In the course of the
      medical audit, all relevant clinical data are reviewed and scored by an internal
      or an external expert (not participating directly in the treatment process), e.g.
      for the adequacy of the medical decision preparative process, conformation to the
      institutional treatment protocol, equipment selection, treatment planning,
      simulation and portal film, etc. If a major deviation is detected, an immediate
      correction is initiated; minor deviations need analysis and then preventive and
      correcting action. As concern the audit of the other activities of the
      departments, the important indicators and their minimally desirable level are
      defined. The final goal of the implementation of this programme is high-precision
      radiotherapy with the best achievable treatment result.

PMID- 8524550
TI  - [Oncologic diagnosis of serous effusions in body cavities (cytologic study and
      evaluation of cholesterol and carcinoembryonic antigen levels)].
AB  - Conventional cytological evaluation of serous effusions often yields border line
      result: apart from positive (malignant) or negative (benign) diagnoses, a
      relatively large part of the findings are "suspicious for malignancy" (P3). In
      the present paper the authors have analysed to what extent contributes the
      determination of cholesterol and CEA levels of ascites and pleural effusion to
      the diagnostic accuracy of cytologically "suspicious" (P3) cases. In 155
      histologically controlled cases, specificity, sensitivity and diagnostic
      efficiency were assessed on the basis of cytology as well as the determination of
      CEA and cholesterol levels. Statistical parameters were determined for each
      method separately and for their combined application. According to the findings,
      cholesterol and CEA levels over 1.16 mmol/l and 2.5 ng/ml, respectively, indicate
      malignancy. In 19 out of 29 cytologically "suspicious" cases (66%), which
      histologically proved to be positive, cholesterol and/or CEA levels were
      elevated. In all of the 12 non-neoplastic "suspicious" cases the two parameters
      were under the cutoff values. The application of an easy and inexpensive
      cholesterol test proves to be a sensitive technique for indicating carcinomatosis
      and it completes adequately the specific cytological evaluation. If clinical
      symptoms speak for tumor, but the cytology is negative, the evaluation of CEA
      level may prove to be useful as far as it can indicate cancer not yet accompanied
      by carcinomatosis.

PMID- 8524551
TI  - [Jet injection, a new method for the induction of anesthesia in children].
AB  - In order to shorten anaesthesia induction and to avoid pain of the intramuscular
      injection, we evaluated the efficacy and safety of midazolam given by a jet
      injector, utilized solely for mass inoculations until now. Premedication with
      midazolam with the jet-injector, indeed, proved to be effective, rapid and safe
      in children. The best results were found in two groups receiving 150-200
      microgram/kg midazolam. Within 5 minutes, it was easy to cannulate a vein in
      children injected by the jet-injector, whereas the effect of intramuscular
      injection developed slowly, within 7 minutes. In the latter group, cannulation of
      the vein was more difficult than in the other groups. The separation from the
      parents and anaesthetic induction were greatly facilitated by midazolam given by
      the jet-injector. Amnesia was present not only for anaesthetic induction but also
      for the injection. Recovery was not more prolonged in those premedicated with
      midazolam with the jet-injector than with midazolam administered by other routes:
      oral, rectal or nasal. The children induced with the aid of jet-injector had no
      unpleasant recall based on interviews with the patients and parents.

PMID- 8524552
TI  - [While science grows and the number of libraries decreases, what will happen to
      information? (Decrease of medical journals in Hungary)].
AB  - The differences between the 1982 and 1994 subscriptions of the leading medical
      journals were investigated. Sample journals were taken from the impact factor
      rank lists of the Science Citation Index. The 1994 level was 45% lower than that
      of 1982. The information supply of the medical universities has weakened too,
      especially because they have too many small institutional library units. They are
      not able to supply the literature necessary to their readers and to the Hungarian
      medical audience.

PMID- 8524553
TI  - Pirenzepine prevents form deprivation myopia in a dose dependent manner.
AB  - Previous studies have demonstrated that muscarinic antagonists, such as atropine
      and pirenzepine, block form deprivation myopia in avian and mammalian models. The
      aim of the present investigation was to establish dose-response curves for
      intravitreal and subconjunctivally injected pirenzepine and to determine receptor
      specificity. Chicks were monocularly deprived of form vision for five days and
      received daily injections of either pirenzepine or saline. Keratometry,
      retinoscopy and A-scan ultrasonography of axial ocular dimensions were then
      taken. Intravitreally injected pirenzepine was effective at preventing form
      deprivation myopia in a dose dependent manner with an ED50 of 175 micrograms. A
      500 micrograms dose totally prevented induced myopia (+0.9 D versus -13.7 D) and
      axial enlargement (-0.14 mm versus +0.32 mm). Daily subconjunctival injection of
      pirenzepine was significantly less effective in preventing form deprivation
      myopia. Form deprivation myopia could still be induced in animals which had
      undergone pirenzepine treatment. Pirenzepine was effective in preventing the
      axial elongation associated with experimental myopia in a dose dependent manner
      and via a functional not toxic mechanism.

PMID- 8524554
TI  - Form deprivation myopia: elastic properties of sclera.
AB  - Thinning of the posterior sclera may imply that stretching and/or weakening of
      the sclera plays a role in axial elongation of myopic eyes. We investigated the
      elastic stress-strain properties of sclera from developing tree shrew eyes made
      myopic by monocular deprivation (MD) of form vision. Five days of MD induced a
      relative myopia (mean +/- SEM) of -5.6 D +/- 0.6 D (retinoscopy) and a vitreous
      chamber elongation (deprived minus control) of 106 +/- 14 microns, n = 10
      (ultrasonography). Posterior scleral test samples (2 mm wide) cut from myopic
      eyes were significantly thinner than their contralateral eye controls (149 +/- 4
      microns versus 164 +/- 4 microns, n = 10, P < 0.01) when measured with a force
      controlled micrometer. However, posterior sclera from control eyes was
      significantly thicker than that from age-matched normal eyes (164 +/- 4 microns
      versus 149 +/- 3 microns, n = 10, P < 0.01). Under uniaxial tension, posterior
      scleral samples from myopic eyes failed at 18% lower load (162 g versus 198 g)
      and extended approximately 25% more than controls at a load corresponding to 20
      mm Hg intraocular pressure. These differences were largely accounted for by the
      differences in scleral thickness. Finite element modelling of tree shrew eyes
      using the material properties summarised above, implies that simple elastic
      stretching of the sclera accounts for less than 20% of the observed difference in
      axial length between myopic and contralateral control eyes.

PMID- 8524555
TI  - Computation of retinal contour in anisomyopia.
AB  - It is well documented that myopia is associated with an increase in axial length
      of the posterior vitreous chamber. Whether equatorial or transverse dimensions
      are likewise affected in myopia is relevant to further understanding of the
      development of ametropia. We have utilised a computing method to determine
      retinal contour from real eye measurements of keratometry, A-scan ultrasonography
      and peripheral refraction as a means of assessing the transverse dimensions of
      the vitreous chamber. This technique has been applied to a 21-year-old female
      Caucasian anisomyope with a refractive error of R -1.50/-0.50 x 130 and L -4.00/
      0.50 x 160. Anisomyopia offers a special opportunity for inter-eye comparison of
      different degrees of myopia. The repeatability of the technique was assessed by
      taking 10 separate sets of the aforementioned measurements and thus generating 10
      retinal contours for each eye. We conclude that this method is repeatable and is
      capable of demonstrating differences between anisomyopic eyes although validation
      against in vivo measurements is required.

PMID- 8524556
TI  - Hazy days? The refractive outlook of photo-refractive keratectomy/photo
      astigmatic keratectomy.
AB  - The refractive outcome of 100 healthy myopic eyes which had undergone excimer
      laser (VISX 20/20) was evaluated at 6 months post-treatment. Patients were
      subdivided into Group A (n = 51, < -5.00 D spherical equivalent (SE)), Group B (n
      = 38, -5.00 to < -10.00 D SE) and Group C (n = 11, > -10.00 D SE). The mean
      myopic sphere decreased from -2.88 to -0.22 DS, -5.94 to -0.43 DS and -12.61 to 
      1.83 DS, respectively. Cylinder reduction ranged from 23 to 53%, effectiveness:
      decreasing with increasing associated myopia. Sixty-six percent of all subjects
      attained an SE correction within 1.00 D of that attempted, however, 80% actually
      achieved vision of 6/12 or better. At 6 months only six eyes were not within one
      line of their pre-operative best spectacle visual acuity (BSVA) and four of these
      exhibited haze greater than Grade 1. In low myopia, photorefractive keratectomy
      (PRK) appears to be highly successful with 93% of subjects with an initial myopia
      of < -5.00 D SE obtaining 6/12 or better vision. However, photo-astigmatic
      refractive keratectomy (PARK) was variable within all groups.

PMID- 8524557
TI  - Contact lens fitting after photorefractive keratectomy: a comparison of two
      groups of patients.
AB  - From a research programme comparing two photorefractive keratectomy (PRK)
      methods, Group S using Summit ExciMed UV 200, and Group V using the VisX 20:20
      excimer laser system, 10 patients from each group were recruited. They were
      referred 6-12 months post-PRK for lens fitting to correct resultant ametropia or
      irregular astigmatism. Ablation zone diameters were: Group S, 4.5 mm; Group V, 4
      6 mm. For Group S, best fit rigid gas permeable (RGP) lenses generally had a back
      optic zone radius (BOZR) 0.10 mm steeper than the mean keratometry reading (K)
      and overall diameter of 9.20-10.0 mm. For Group V best fit RGP lenses generally
      had a BOZR of 0.20 mm steeper than the mean K. The lenses often required large
      diameters to improve lens centration and extra negative power to compensate for
      the positive power of the central tear pool. Several patients required soft lens
      fitting to improve comfort and some finally opted for repeat PRK.

PMID- 8524558
TI  - The pre-myopic syndrome.
AB  - Considering the social importance of myopia in industrialised countries, this
      study aimed to research criteria which could determine whether a person might
      become myopic. For this purpose, a sample of 25 emmetropic (plano to +0.75 D)
      subjects, who became myopic during the 2 years following the initial eye
      examination (the pre-myopic group), were compared to a matched sample of subjects
      who did not become myopic during the same period. The results show at the 95%
      statistical level of confidence, that the pre-myopes have particular
      characteristics, such as a loss of physiological hyperopia, a more positive near
      retinoscopy and near cross-cylinders and tendency to esophoria. The test of
      dioptric variations* points to a decrease in the dynamics of accommodation as
      well as non-overlapping of near and far comfort zones.

PMID- 8524559
TI  - Shared care, past and future.

PMID- 8524560
TI  - The cost of monitoring glaucoma patients by community optometrists.
AB  - Glaucoma patients are currently undergoing monitoring by community based
      optometrists as part of a randomised controlled trial of shared care. As part of
      this trial, the costs of monitoring these patients by community optometrists are
      being calculated. Data were obtained from eight practices for the 1993-1994
      financial year. The average 'full' cost of a 40 min appointment was calculated as
      epsilon 31.56 pounds. The average number of unbooked appointments for the month
      of October 1994 was 16 per practice, which equated to 12, 40 min appointments.
      Once the number of unbooked appointments was surpassed for each practice, an
      average opportunity cost of epsilon 54.00 pounds was experienced per appointment.
      The participating optometrists were willing to accept a minimum fee of epsilon
      26.03 pounds for a small number of patient assessments but this rose to epsilon
      43.16 pounds for up to 100 glaucoma patients seen per annum.

PMID- 8524561
TI  - Detecting progressive visual field loss.
AB  - Involvement in shared care projects requires the optometrist to make a series of
      decisions one of which is an assessment of the visual field data to see if there
      has been any progression. To aid the optometrist in making this decision, the
      relationship between inter-test variability in the visual field and extent of
      loss has been established for the Henson CFS2000 perimeter. In this study, visual
      field data were collected, with a supra-threshold strategy, from 174 eyes (89
      patients) over a period of 2 years, there being a total of 595 visual field
      records. The sample included patients with both normal and glaucomatous visual
      fields. The results show that analysis based upon the number of stimuli missed at
      5 or more dB above the threshold estimate reveals an increasing variability with
      extent of loss. These data can be used by optometrists to establish the
      significance of any change in the number of missed stimuli from one visit to the
      next.

PMID- 8524562
TI  - The Bristol Shared Care Glaucoma Study: study design.
AB  - The purpose of this study was the evaluation of community based optometric
      monitoring of stable glaucoma patients and glaucoma suspects compared to the
      routine Hospital Eye Services (HES) monitoring. Four hundred and five subjects
      were recruited from routine outpatient clinics at the Bristol Eye Hospital. All
      eligible participants were seen in the routine hospital clinic and then within
      two months were given a 'Gold Standard Assessment' (GSA) by an independent
      research team. Participants then visited one of 12 glaucoma-trained optometrists,
      for a standard battery of tests. Randomisation resulted in 204 subjects being
      allocated to community care, with reviews on a six monthly basis, with 201 who
      remained a control group within the hospital. Referral criteria were established
      to enable optometric detection of apparent glaucomatous progression. A
      questionnaire was used to assess patient satisfaction with both care types.
      Additionally a cost analysis exercise was performed.

PMID- 8524563
TI  - Amblyopia: a tale of two approaches.
AB  - Our understanding of the physiological basis for amblyopia in humans has
      undergone dramatic changes over the past two decades. The first such change
      occurred when we were first able to record from single neurones in different
      parts of the visual pathway and develop neural models of the anomaly. The second
      came from psychophysical investigations and evaluations of these animal models.
      Our understanding has progressed from one focused on the properties of single
      cortical cells to an appreciation of the anomalous behaviour of cellular
      networks.

PMID- 8524564
TI  - Different uses of chromatic signals in patients with congenital and acquired
      colour vision deficiencies.
AB  - Chromatic signals can be used to generate perceived colour and also to detect
      spatially structured objects defined only by chromatic differences. These two
      attributes have previously been investigated in dichromats and cerebral
      achromatopsic patients using a new colour vision test developed at City
      University that makes possible the isolation of pure chromatic signals (Barbur et
      al. Proc. R. Soc. London B 258, 327-334, 1994). We have investigated acquired
      colour vision changes in a 69-year-old patient, after conventional colour vision
      tests gave ambiguous results. His ability to detect an object using chromatic
      signals was impaired more than his ability to detect a colour change, and this
      impairment was greater in the right eye than in the left eye. This dissociation
      suggests parallel pathways may be involved in the two processes of coding
      chromatic signals. Recent neurological testing on the same patient has indicated
      the onset of multiple sclerosis. Our much earlier finding based on colour vision
      testing may therefore have useful diagnostic implications.

PMID- 8524565
TI  - A new computerised video-aberroscope for the determination of the aberration of
      the human eye.
AB  - We have developed a video-based system for the acquisition and analysis of images
      produced by an aberroscope. The aberroscope uses a helium-neon laser to project a
      shadow image of a grid onto the retina. The retinal image is, in its turn, imaged
      onto a CCD video camera. As the grid forms a shadow image, the position of each
      grid intersection at the retina is affected by the aberrations of the eye. The
      emergent beam is imaged by the whole pupil, hence the grid shape is little
      affected by the eye's optics. We compute the aberrations of the eye by measuring
      the distortions of the grid. A video-digitiser converts the video camera image
      into data that can be processed by an Apple Power Macintosh computer using an
      image processing program (NIH Image V1.57). The program locates the grid
      intersection positions and computes the coefficients of a Taylor polynomial that
      describes the wavefront aberration. This technique has significant advantages
      over photographic methods that use manual image assessment. It gives immediate
      image storage and analysis, the ability to screen out poor quality images,
      requires significantly less or no operator interaction and is less labour
      intensive.

PMID- 8524566
TI  - Automated static perimetry in myopes with peripapillary crescents--Part I.
AB  - Central visual fields were investigated by automated static perimetry in a group
      of healthy myopic individuals with peripapillary crescents and tigroid fundus
      changes only. Results were compared with 'emmetropic' and 'myopic subjects
      without crescents' control groups. The sample comprised 122 young, healthy
      volunteers between the ages of 18.5 and 35.4 years, free from any ocular or
      systemic disease, with refractive errors ranging from +4.00 D to -25.75 D.
      Central visual fields were examined using programs 30-2 and 30-1 of the Humphrey
      Field Analyzer (HFA), which in combination yield a test point resolution of 4.2
      degrees within the central 30 degrees. Visual field analysis showed a decline in
      the differential light sensitivity in myopes with peripapillary changes only,
      compared with the control groups. These field changes became more pronounced as
      the degree of myopia, axial length and area of the peripapillary crescent
      increased. Results suggest that the sensitivity decline of the central field
      occurs in subjects with axial lengths above 26 mm and more than 5 D of myopia.
      Knowledge of the likely field defects encountered in myopia will assist
      practitioners to distinguish between physiological and pathological fields in
      myopes.

PMID- 8524567
TI  - A quantitative analysis of eye movements during the cover test--a preliminary
      report.
AB  - The aim of this study was to carry out quantitative analyses of eye movements
      during the cover test on a group (n = 57) of asymptomatic emmetropes. Eye
      movements were recorded during an automated cover test while subjects fixated a
      distance (3.4 m) and near (0.4 m) target. There was a significant difference
      between the amplitude of phoria measured after 2 s of occlusion compared to 10 s
      (P < 0.01). The mean phoria after 10 s of occlusion was 0.1 degree (eso) for
      distance fixation and 1.6 degrees (exo) for near fixation. The distribution was
      approximately normal for both distance and near fixation but the standard
      deviation was greater for near (2.0 degrees) than distance fixation (1.4
      degrees). The pattern of eye movements during the recovery phase was more complex
      than is often assumed, in many cases consisting of a variety of saccadic and
      vergence movements involving both the covered and 'fixing' eye. The latency of
      the first recovery movement was significantly shorter for exophoric than
      esophoric deviations (P < 0.01) and the latency of some recovery movements were
      very short (< 150 ms).

PMID- 8524568
TI  - Establishing the threshold prior to single and multiple stimulus supra-threshold
      strategies.
AB  - The purpose of this study was to establish whether the routines used to establish
      the threshold at the beginning of single and multiple stimulus supra-threshold
      strategies yield the same values and whether data from one strategy can,
      therefore, be compared with those from the other without having to compensate for
      a difference in test intensities. Single stimulus and multiple stimulus supra
      threshold strategies were conducted on 79 subjects using a Henson 4000 perimeter.
      On average the multiple stimulus strategy gave a value 0.095 dB higher than the
      single stimulus strategy. The differences between the two strategies was so small
      that results from the two strategies can be compared without having to compensate
      for any changes in the supra-threshold test intensity.

PMID- 8524569
TI  - The Pulfrich effect in optometric practice.
AB  - The Pulfrich effect can occur spontaneously, giving severe symptoms of changed
      visual perception in a variety of conditions in which an interocular latency
      difference has occurred. The symptoms principally involve misjudgements on the
      location of objects, especially when driving. Interocular latency differences can
      inadvertently be created in patients in practice and this study has investigated
      the Pulfrich effect in anisocoria, uniocular mydriasis, and with uniocular tint
      (X-chrom lens). In all cases a Pulfrich effect was consistently evident and
      compared to the size of the effect provoked by neutral density filters. The
      results show that with anisocoria, uniocular mydriasis and the X-chrom lens, the
      provoked Pulfrich effect is similar to that found reported previously in cases of
      trauma. These cases had severe visual symptoms so that care should be exercised
      in practice, where procedures likely to provoke the Pulfrich effect are
      contemplated. Specifically, patients who have received uniocular mydriasis in
      practice should be cautioned about the possible visual effects and advised not to
      drive until the effect of the mydriatic has finished and equal pupil sizes have
      been restored.

PMID- 8524570
TI  - The aetiology of presbyopia: a summary of the role of lenticular and
      extralenticular structures.
AB  - Presbyopia is a condition of age rather than ageing and, as such, is devolved
      from the lamentable situation where the normal age-related reduction in amplitude
      of accommodation reaches a point when the clarity of vision at near cannot be
      sustained for long enough to satisfy an individual's requirements. Most of our
      facility to accommodate has been lost by 55 years-of-age and subsequent
      deterioration in visual performance at near is attributable to characteristics of
      senescent vision familiar to the optometrist. Our understanding of the cause of
      presbyopia has then to be derived principally from our understanding of the
      mechanism of accommodation in young eyes. Hermann von Helmholtz did much to
      clarify these mechanisms, but despite much research in the 100 years since his
      death, there is still no consensus on their precise nature. This paper presents a
      summary of issues, past and present, which have figured in the literature on the
      physiology of accommodation and presbyopia, and confirms that the pathophysiology
      of presbyopia is likely to result from deterioration in structure and function of
      a number of inter-related tissues. Changes in crystalline lens dimensions with
      age, the associated change in geometry of zonular attachments, and changes in
      viscoelastic properties of the lens capsule and lens matrix would, however,
      appear to be the principal correlates for the onset of presbyopia. Recent models
      of the biomechanics of accommodation have drawn attention to the feasibility of
      extralenticular contributions to presbyopia and have examined properties of the
      elasticity and leverage provided by posterior, anterior and tensile fibre
      systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524571
TI  - Broken down by age and sex. The optical correction of presbyopia revisited.
AB  - New transverse clinical data are presented which describe the time course of
      presbyopia, as indicated by the temporal change in magnitude of the binocular
      spectacle add, in normally sighted male and female Caucasian subjects. An initial
      steep increase in add requirement beginning in the early forties becomes
      relatively slower but still of significance beyond the mid-fifties. This
      observation is correlated with the age-related progressive decline in the
      amplitude of accommodation, itself a consequence of physiological changes in the
      crystalline lens and capsule. The continuing need for an increase, albeit at a
      reduced rate, in the positive near supplement beyond the mid-to-late fifties (by
      which time little or no useful accommodation is available), is now attributed to
      the visually disruptive effects within the high spatial frequency domain of
      progressive age-related lenticular changes. The magnification afforded by the
      positive add increases spatial grain and thereby enhances visibility of detail in
      an ageing visual system free of any gross senile pathology. A small but
      consistent gender difference (congruent to 0.1 D) is revealed in presbyopic
      corrections: physiological and (more probable) physical bases are suggested for
      the observation that females require an add of greater magnitude than their age
      matched male counterparts.

PMID- 8524572
TI  - The fluctuations of accommodation and ageing.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of age on the
      fluctuations of accommodation. METHOD: Fluctuations of accommodation were
      measured on six 'young' (16-25 years, mean age 22 years) observers and six
      'older' (35-48 years, mean age 42 years) observers. Accommodation was
      continuously recorded using a SRI optometer whilst the observers steadily viewed
      a high contrast target at stimulus levels 0.25 D, 1.00 D and 2.00 D. Fluctuations
      were quantified using power spectrum analysis, and frequencies were grouped into
      bands: low (LFC 0.3-0.6 Hz and 0.3-0.9 Hz) and high (HFC 1.1-2.2 Hz). RESULTS:
      Accommodation response levels for these stimuli for both groups of observers were
      quite similar. Fourier analysis was used to generate power spectra so that the
      fluctuations of accommodation for each observer group could be compared. In
      general power increased for increasing response levels for both groups of
      observers, although less power was evident for the older observers in both LFC
      and HFC bands. Differences in power were not significant at these frequency bands
      for the two observer groups. When the whole power spectrum is compared these
      differences became significant with more power evident in the younger cohort.
      CONCLUSION: Reductions in both amplitude and speed of accommodation with age are
      well known, and the decline in magnitude of the fluctuations found here is
      consistent with a general diminution in accommodation dynamics as the
      accommodation mechanism ages. For the older group, some of who were near absolute
      presbyopia, there may be little contribution to power from changes in lens shape
      and it is possible that small changes in lens position in the eye contribute to
      the power spectrum.

PMID- 8524573
TI  - Effect of age on the interaction between the AC/A and CA/C ratios.
AB  - A number of previous studies have examined the effects of age and the development
      of presbyopia on either the accommodative convergence to accommodation (AC/A) or
      convergent accommodation to convergence (CA/C) ratios. However, changes in the
      interaction of these oculomotor crosslinks with increasing age have received
      relatively little attention, especially over a wide age distribution.
      Accordingly, the present study examined both crosslink ratios in 42 subjects
      ranging from 22 to 65 years of age. A dual haploscope-optometer was used to
      measure accommodation and vergence. The response AC/A ratio showed a small but
      significant positive correlation with age in those subjects under 45 years of
      age, while no significant correlation was observed between the stimulus AC/A
      ratio and age for all subjects. The CA/C ratio exhibited a significant negative
      correlation with age for all subjects. Furthermore, a trend was observed for
      lower CA/C findings to be associated with higher response AC/A ratios. However,
      the two ratios were inversely but not reciprocally related, with the mean
      difference between the CA/C ratio and the reciprocal of the response AC/A ratio
      being significantly different from zero. These age-related changes in the output
      of the oculomotor crosslinks provide further evidence of the continual oculomotor
      adaptation that occurs concurrent with the loss of accommodative responsivity.

PMID- 8524574
TI  - Varifocal contact lenses for the correction of presbyopia.
AB  - A Nissel +1.75 D PS45 lens' label power seems to be made up of about +0.75 D
      distance and +0.75 D near addition. There are individual variations which will
      depend on pupil size, corneal shape, lens position and ocular aberrations. When a
      +0.75 Bausch & Lomb U3 lens was used as a control, there was also a significant
      increase in 'accommodation' measured (+0.75 D), but this could not be explained.
      When two other lenses with an aspheric surface were studied, they also showed a
      near addition effect. In this supplementary study the changes were explained by
      changes in spectacle accommodation. A lens with two spherical surfaces did not
      show the expected increase in spectacle accommodation. Astigmatism, as a general
      rule, was not corrected by the PS45 lens, although the very occasional case did
      show some reduction. Visual acuity and contrast sensitivity at 8 cpd and 3 cpd
      were not significantly affected when compared to the control lens.

PMID- 8524575
TI  - Correlation between presbyopia, age and number of births of mothers in the Kumasi
      area of Ghana.
AB  - There is an assumption in Ghana that motherhood has an effect on presbyopia. This
      study thus attempts to correlate the relationship between presbyopia, age and
      number of births of mothers in the Kumasi area of Ghana. The data were compiled
      from records of patients who attended routine eye examinations and refraction
      tests at the Morny Optical Centre, Kumasi, during the last quarter of 1993.
      Presbyopia in males and females, and those of mothers and childless female adults
      for particular age groups were compared. Correlations were found between age and
      reading additions for both sexes, and presbyopia occurs at a younger age than
      published. This preliminary study does not indicate any inter-dependence of
      births on female presbyopia. Further studies with select data may be required to
      confirm the above findings.

PMID- 8524576
TI  - Research support by the British College of Optometrists.
AB  - The British College of Optometrists has now been in existence for 15 years. One
      of its first actions was to establish a formal system of research support. The
      initiation of the scheme and its subsequent expansion is described. In the first
      year epsilon 5,000 pounds was allocated but current expenditure for 1994/1995 is
      epsilon 78,671 pounds. Research topics funded are described as are the award of
      higher degrees by universities and also the current occupation of former
      scholars. The thesis submission rate for college scholars compares well with
      those of the major established Research Councils.

PMID- 8524577
TI  - Role of peripheral vision in terms of critical perception--its relevance to the
      visually impaired.
AB  - It is recognised that discrimination of fine detail is dependent on an intact
      macula with the peripheral retina being responsible for motion detection. There
      is evidence, however, to suggest that the peripheral retina does play a critical
      part in such discrimination. Studies of the performance of visually impaired
      school children have revealed levels of visual perception far exceeding anything
      that would be expected for individuals so severely handicapped. The art work of
      visually impaired youngsters was compared with the predicted results based on
      their visual acuity. The results showed detail that in theory could not have been
      resolved with such low acuity levels. All the youngsters had dense central
      scotomata. The peripheral retina, therefore, must have been involved in the
      discrimination of such detail. These results have implications not only for the
      visually impaired in terms of what they are capable of doing, but also for our
      understanding about the way the visual cortex processes information from the
      peripheral retina and the use that it makes of this relatively poor quality
      information.

PMID- 8524578
TI  - Reversal of tropicamide mydriasis with single instillations of pilocarpine can
      induce substantial pseudo-myopia in young adults.
AB  - Pupillary dilation for diagnostic purpose has become an increasingly common
      procedure in UK optometry in recent years and the consensus seems currently to
      militate against the routine use of miotics; an eye that is judged safe to dilate
      is thought to be at minimal risk during the natural recovery phase to normal
      pupil size. Nevertheless, the optometrist does, on occasion, need to consider
      whether there might be some advantage in minimising the sometimes debilitating
      effects of cycloplegia and mydriasis produced in young adults by tropicamide. In
      this context we compare the effects of single instillations of two miotic agents:
      the alpha-adrenoceptor antagonist thymoxamine HCl (0.5%), and the
      parasympathomimetic pilocarpine HCl (1 and 2%). Tropicamide was used to induce
      mydriasis in a group of 12 volunteer student subjects aged 20-26 years (7 males,
      5 female; mean 21.67 years) selected to provide low (L; n = 4), medium (M; n = 4)
      and high (H; n = 4) iris pigment levels. Measurements of pupil diameter (Brocca
      pupillometer), Snellen visual acuity and accommodative amplitude (near point
      rule) were made every 3 min over a 90 min recording period for 4 trials: (1) a
      control condition whereby a miotic was not employed; (2) thymoxamine HCl 0.5% was
      instilled after 30 min; (3) and (4) pilocarpine 1% and 2% was instilled after 30
      min, respectively. Tropicamide induced a mean increase in pupil area from 25 to
      50 mm2 after 22 min which was generally sustained over the 90 min period and was
      enhanced for the lower pigment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524579
TI  - Optometric correlates of Meares-Irlen syndrome: a matched group study.
AB  - People who report visual perceptual distortions, typically when reading, that are
      alleviated by using coloured filters are described as suffering from 'Meares
      Irlen Syndrome'. A recent double-masked placebo-controlled trial showed that this
      condition cannot be solely explained as a placebo effect and that the beneficial
      filter is idiosyncratic and sometimes needs to be highly specific. Several
      mechanisms have been suggested for Meares-Irlen Syndrome including ocular motor
      (binocular and accommodative) anomalies, a sensitivity to patterned stimuli
      (pattern glare), and a deficit of the transient visual sub-system. We
      investigated these hypotheses by comparing 16 children, who reported the symptoms
      described above and who showed a sustained benefit from coloured filters, with 25
      control children who came from the same school and were matched for age, reading
      performance and intelligence. The 'Meares-Irlen Syndrome' group had slightly, but
      significantly, reduced vergence and accommodative amplitudes and stereo-acuity;
      they also demonstrated significantly more pattern glare. The two groups did not
      differ significantly in their visual acuities, refractive error, dissociated or
      associated heterophoria, AC/A ratio, or ability to perceive 20 Hz flicker. It
      appears that certain ocular motor factors are correlates of Meares-Irlen
      Syndrome, rather than the primary underlying cause of the symptoms. The results
      support the hypothesis that pattern glare may be involved in the mechanism of
      Meares-Irlen Syndrome.

PMID- 8524580
TI  - Ocular dysfunction associated with mental handicap.
AB  - The aim of this article is to show the main general and ocular characteristics of
      a group of 46 mentally handicapped people of different IQ and age who were
      provided with visual care. Many different syndromes and neurological alterations
      have been described in the literature. The case types and number of people
      studied for each condition attending our clinics were: syndromes: Down's (25),
      Soto (2), West (2), Rubinstein-Taybi (1), triple X (1); neurological conditions:
      cerebral palsy (8), microcephaly (5), hydrocephaly (2). In our study the ocular
      findings were high incidence of ametropies: 58.7% hyperopia, 21.7% myopia, 19.5%
      astigmatism and 28% strabismus.

PMID- 8524581
TI  - Intraocular motility, electrophysiological tests and visual fields in drug
      addicts.
AB  - The effects of drugs on intraocular motility, retina function and central
      pathways in a drug addicts population have been studied. The study group were
      made up of 15 drug addicts. Fifteen healthy subjects who had never used drugs
      acted as a control group. Refractive state, accommodation, tonometry, assessment
      of pupillary reflexes, campimetry, visual evoked cortical potential (VECP) and
      ERG were performed in all cases. All the subjects studied used heroine, 12 used
      cannabis and 12 used cocaine. Refraction was normal in all cases. Accommodation
      amplitude in normal subjects ranged from 8.5 to 11.5 D, and from 3.5 to 9.5 D in
      the drug addicts group. Tonometry indicated a tendency to lower intraocular
      pressure values. Direct and consensual pupillary reflexes were normal in eight
      subjects, but were sluggish in the rest. Campimetry showed relative and absolute
      scotoma in five subjects. VECP were found to be normal in two of the cases,
      moderately pathological in six and pathological in the remaining seven cases. As
      for the ERG, it showed non-specific altered traces in 11 cases. Accommodation
      amplitude was lower than normal in 20 eyes. The decrease of VECP with altered
      traces but with an increase of latency, seem to indicate the presence of an
      alteration in the optical pathway or in the cortical centres. The findings in ERG
      point out a decrease of amplitudes and an increase of latency in more than half
      the population studied.

PMID- 8524582
TI  - The lacrimal lens as an assessment factor in hard contact lens fitting.
AB  - The fitting of hard contact lenses relies primarily on the evaluation of the
      findings of 'K' readings, the fluorescein pattern of the tear configuration and
      the interpretation of the lens movement upon blinking and the lens position after
      blinking. All of these methods have some disadvantages in the evaluation
      procedure: (a) keratometer readings measure cornical radius in a small and
      restricted area of the central cornea not in the larger area to eventually be
      covered by the lens (Bennett and Rabbetts, Clinical Visual Optics. Butterworths,
      London, UK, pp. 420-421, 1984); (b) the fluorescein pattern is sometimes
      unreliable especially in the presence of excessive tear flow; (c) lens movement,
      arguably the most reliable of evaluation methods, nonetheless requires some
      alternative back-up technique. This presentation outlines the possibility of
      utilising the lacrimal lens as a useful additional procedure to the above when
      prescribing a lens curvature of choice. It should be pointed out that the
      technique discussed refers to spherical or near spherical corneas.

PMID- 8524583
TI  - The magnocellular deficit hypothesis in dyslexia: a review of reported evidence.
AB  - Many reports suggest that the majority of dyslexic children have a measurable
      disorder of the fast processing pathway of the visual system. This pathway is
      believed to extend from the retina to the occipital and parietal areas of the
      brain, and is referred to as the magnocellular (M) or transient pathway. Evidence
      in support of the magnocellular deficit theory comes from several sources, but is
      not totally consistent. Histological studies have revealed shrinkage and
      disorganisation of M cells in the lateral geniculate nucleus of dyslexic
      subjects. Psychophysical investigations of visual persistence, contrast
      sensitivity to moving sine wave gratings and flicker sensitivity, report atypical
      results in dyslexic children, reflecting an apparent deficiency in the transient
      system, although not all psychophysical studies have demonstrated such a
      deficiency. Visual evoked potential responses to a wide range of stimuli have
      been reported to be deficient in dyslexic subjects, but again there are
      dissenting papers. These reports have been subject to critical review and
      analysis, new techniques specifically to stimulate the magnocellular pathway are
      described, and the relevance of this research to tinted lens therapies and
      clinical reading problems is discussed.

PMID- 8524584
TI  - A new protocol for the optometric management of patients with reading
      difficulties.
AB  - Research by Evans et al. (Ophthal. Physiol. Opt. 15, 481-487, 1995) has
      demonstrated a correlation between visual processing and ocular motor factors in
      people with specific reading difficulties (dyslexia). In addition, research by
      Wilkins et al. (Ophthal. Physiol. Opt. 14, 365-370, 1994) has shown that some
      people with dyslexia will benefit from a reduction of perceptual symptoms of
      discomfort and distortion if they use individually prescribed coloured filters.
      Three examples of the dyslexic patients who attend at the Institute of Optometry
      clearly demonstrate the importance of full investigation of ocular function,
      including the assessment of the effect of colour on visual perception. All three
      patients presented with similar symptoms of asthenopia when reading. Symptoms
      were alleviated for the first patient by use of orthoptic treatment of an
      exotropia with intermittent suppression. With the second patient, ocular motor
      functions were found to be within acceptable limits and relief of symptoms was
      obtained by the prescribing of lenses of a specific chromaticity. For the third
      patient, both orthoptic intervention and the use of specifically tinted lenses
      were necessary to relieve the visual difficulties that were being experienced. By
      taking advantage of recent research and developments in optometric
      instrumentation, it is possible for some of those with dyslexia to receive
      considerable benefit from optometric intervention.

PMID- 8524585
TI  - Is there a visual deficit in dyslexia resulting from a lesion of the right
      posterior parietal lobe?
AB  - Dyslexia has conventionally been attributed to a left hemisphere deficit
      affecting language skills. However, it has recently been suggested that two
      thirds of dyslexic people have a lesion of the right posterior parietal lobe
      (RPPL) resulting in poor oculo-motor control. It has been reported that
      neurological patients with RPPL lesions commonly manifest a neglect of the left
      side of space and this has also been described in clinical observations of
      'visual dyslexics'. We investigated this hypothesis with a sample of 53 dyslexic
      children and 53 controls using a line-bisection task. In the horizontal test
      condition both groups tended to transect slightly to the left of the midpoint
      (mean displacement 0.14 mm for controls; 0.4 mm for dyslexics). The result
      suggests a small right side neglect which, contrary to one report in the
      literature, is found here in developmental dyslexics as well as controls, and
      leads to the conclusion that RPPL lesion is unlikely to be a common feature of
      dyslexia.

PMID- 8524586
TI  - Visual training programme applied to precision shooting.
AB  - A three month visual training programme was conducted at the CAR of Sant Cugat
      (Olympic Training Center). Eleven members of 'The Catalan Government Special
      Intervention Squad' were used in a clinical trial. Pre-test and post-test results
      were obtained for pistol shooting, visual function, and psychological and
      physical states. Statistical analysis indicated significant gains in visual
      function and pistol shooting scores after the programme, while psychological
      (anxiety) and physical condition remained the same. Some conclusive statements
      can be made with regard to the relation of visual function improvement and
      shooting performance increment, after analysing the data. This improvement is
      evident in statistically significant post-test gains in the following variables:
      'phoria at distance, recovery points in fusional reserves at distance, analytical
      amplitude, negative relative accommodation, saccadic fixations, and accommodative
      facility at distance and at near. The rest of the controlled visual variables
      also showed clinical improvement.

PMID- 8524587
TI  - Is there a need for binocular vision evaluation in low vision?
AB  - The purpose of this study was to determine the need for a binocular vision
      evaluation in the management of low vision patients. Thirty subjects were
      selected with visual acuities of at least 6/60 in each eye. Twenty-three had age
      related macular degeneration as the primary ocular pathology and seven had
      various other ocular conditions. The binocular vision evaluation comprised:
      detailed history and symptoms with an emphasis on the occurrence of near vision
      problems; modified binocular vision assessment which included cover test at near,
      ocular movements, convergence, Bagolini glasses, horizontal vergence reserves and
      prismatic measurement of any observed anomaly. History and symptoms revealed
      horizontal and vertical diplopia, jumbling of print, asthenopia, intermittent
      blurring and print being too small. Binocular vision assessment revealed
      exophoria at near, manifest horizontal deviations, convergence insufficiency, and
      vertical muscle imbalance. These anomalies occurred either singly or in
      combination. The results indicate that there is a need for binocular vision
      evaluation in low vision in order to reveal near vision disorders that may be
      partly attributable to binocular vision anomaly and not solely due to ocular
      pathology. This information should facilitate the implementation of the
      appropriate course of optometric management for these patients.

PMID- 8524588
TI  - Surface wettability and hydrophilicity of soft contact lens materials, before and
      after wear.
AB  - Surface wettability and hydrophilicity of pHEMA soft contact lenses were
      investigated utilising adherent liquid/laser method (ALLM) and adherent
      liquid/balance method (ALBM). The measurements were carried out before and after
      periods of 15 min to 2 h contact lens wear. Following the lens removal, the
      wetting angle of the contact lens of the left eyes and hydrophilicity (maximum
      force) of the contact lens of the right eyes of the five subjects were
      immediately measured, respectively, without cleaning (one value for pre-lens wear
      and eight values for post-lens wear). The wettability of soft contact lenses
      significantly increased after 15 min of wearing and stabilised at a maximum level
      after 30 min in vivo. Contact lens hydrophilicity was found to decrease as the
      lens was worn. The reduction continued for up to 1.5 h of wearing, for male
      cases, and for the female cases, the reduction continued until the end of the
      experiment.

PMID- 8524589
TI  - Managed care: physicians can build it better.
AB  - Managed care is the prime item of discussion at the Pennsylvania Medical Society
      these days. The commonwealth now is listed as one of the top five states in the
      growth of HMOs and other managed care delivery, and this marketplace trend toward
      managed care is having a tremendous impact on the members of the Society.

PMID- 8524590
TI  - 10 good reasons to stay independent. For private-practice physicians thinking
      about selling their practices.

PMID- 8524591
TI  - Integration insider. Analysis of the emerging health care marketplace in
      Pennsylvania and beyond.

PMID- 8524592
TI  - Lessons from Pennsylvania's managed care history.

PMID- 8524593
TI  - Members' outcry heard by Medicare regulators.

PMID- 8524594
TI  - Practice policies must do more today. The Health Care Group.

PMID- 8524595
TI  - You can help promote use of mammogram benefit.

PMID- 8524596
TI  - Managed care changing scope of society subsidiaries.

PMID- 8524597
TI  - Where are all the health care dollar$ going?

PMID- 8524598
TI  - Lincoln's words ring true in DC.

PMID- 8524599
TI  - 10 reasons why physician organizations will succeed.

PMID- 8524600
TI  - Spinal cord transplants: a future treatment for spinal injury?

PMID- 8524601
TI  - Mechanisms underlying the recovery of lower urinary tract function following
      spinal cord injury.

PMID- 8524602
TI  - Motor recovery of patients presenting with motor paralysis and sensory sparing
      following cervical spinal cord injuries.
AB  - We studied the neurological progress of 21 consecutive patients with cervical
      spinal cord injuries, presenting with sensory sparing but with complete motor
      paralysis below the level of their injury (Frankel B). All patients were admitted
      within 48 h of injury and treated conservatively with 6 weeks of bedrest and
      traction, followed by 6 weeks of bracing. The follow-up period was more than 1
      year (49.6 months on average). Despite the initial absence of motor power in the
      lower limbs, seven patients recovered significant motor power and were able to
      walk. The preservation of pinprick sensation between the level of the injury and
      the sacral dermatomes was the best prognostic indicator for useful motor recovery
      with 75% of the patients regaining the ability to walk. This pattern of sensory
      sparing predicted a statistically significant better motor outcome than other
      patterns of sensory sparing. Although 50% of patients with no sacral sensation
      and/or with anal sensation on rectal examination recovered motor power, this
      recovery was functional in only one out of eight patients.

PMID- 8524603
TI  - Superiority of motor level over single neurological level in categorizing
      tetraplegia.
AB  - The purpose of this paper is to demonstrate the superiority of the American
      Spinal Injury Association motor level (ML) and upper extremity motor score (UEMS)
      to the neurological level (NL) in determining self care function in motor
      complete tetraplegia. Fifty subjects with traumatic motor complete tetraplegia,
      NL C4-C8, were evaluated at admission and 12 months post injury. At both time
      periods NL, ML, and UEMS were determined. At 12 months, reported ability to
      perform six feeding activities of the Quadriplegia Index of Function (QIF) were
      documented. Spearman correlations of the NL, BML, WML, UEMS, and feeding QIF
      scores were conducted, and results were compared with t tests for significant
      differences. Both the best and worst ML were more highly correlated to the UEMS
      than was the NL (0.96 and 0.96 vs 0.66, P < 0.001). The best and worst ML were
      more highly correlated to the QIF feeding score than was the NL (0.74 and 0.72 vs
      0.56, P < 0.05). The UEMS had the highest correlation to the QIF feeding score,
      0.78. These results suggest that the NL is an imprecise descriptor of the
      impairment in SCI, and is therefore a poor predictor of the resultant disability.
      The ML and the UEMS better reflect the severity of impairment and disability
      after motor complete tetraplegia.

PMID- 8524604
TI  - Influence of electrical stimulation of the tibialis anterior muscle in paraplegic
      subjects. 2. Morphological and histochemical properties.
AB  - In adult paraplegic subjects one tibialis anterior muscle received daily
      electrical stimulation for 4 weeks at twice the motor threshold to determine
      changes of morphological and histochemical profiles (this paper) and of
      contractile properties (preceding paper). Bilateral biopsies, obtained 4 weeks
      before, and immediately after, electrical stimulation, were studied for fibre
      type proportions, fibre diameters, oxidative capacity, microvasculature and
      histopathology. Before stimulation the biopsies showed disuse with increased type
      2 fibre proportions and decreased oxidative capacity (succinate dehydrogenase
      (SDH) activity). The effects of two stimulus patterns were compared. Following
      stimulation SDH activity increased significantly in all stimulated muscles.
      Inconsistent changes occurred in fibre type proportions, fibre diameters,
      capillary density and capillary/fibre ratios. Both stimulus patterns evoked
      similar results. In five/seven subjects subsarcolemmal vacuolation was observed.
      Electrical stimulation for 4 weeks at only twice motor threshold improves
      oxidative capacity, but different stimulus parameters are probably needed for
      significant fibre type conversion.

PMID- 8524605
TI  - Vesical urothelium proliferation in spinal cord injured persons: an
      immunohistochemical study of PCNA and MIB.1 labelling.
AB  - Urinary tract infection occurs more commonly, is more virulent and proves more
      difficult to eradicate in spinal cord injury persons than in the neurologically
      intact. In order to find out the peculiarities of the neuropathic bladder which
      make it vulnerable to recurrent cystitis, we studied the proliferation status of
      the urothelium in spinal cord injured persons. Eleven consecutive, unselected
      male spinal cord injury patients (aged 18-73 years) were included in the study.
      Those with, or undergoing treatment for acute urinary tract infection were
      excluded. All patients underwent cystoscopy and cold cup bladder biopsy from the
      trigone and bladder dome. Immunocytochemical analysis was performed using
      defined, commercially available antibodies for PCNA (PCNA 10, DAKO) and MIB-1
      (raised against recombinant DNA defined segment of Ki-67 antigen DAKO)
      streptavidin/biotin and alkaline phosphatase immunocytochemistry (for MIB-1 with
      microwave-enhanced antigen retrieval) were used to demonstrate the presence of
      cell cycling-associated nuclear proteins. Foci of lymphocytic aggregations
      present in the sections served as in-section controls for antigen preservation.
      Ten patients showed labelling of 20-70% of cells for PCNA in basal cell layers of
      dome lining. Higher urothelial layers showed a variable, but generally reduced
      degree of labelling. Of these 10 patients, three showed complete absence of MIB-1
      activity in the basal and other layers of dome urothelium and two demonstrated
      only a very occasional positive nucleus. MIB-1 labelling was < 5% in four others
      and it was between 5% and 10% in one.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524606
TI  - Cutaneous ileocystostomy (a bladder chimney) for the treatment of severe
      neurogenic vesical dysfunction.
AB  - The aim of this study was to investigate the efficacy and morbidity of cutaneous
      ileocystostomy, as an alternative to cystectomy and ileal conduit urinary
      diversion, for patients with end-stage neurogenic vesical dysfunction. Three male
      and eight female patients, mean age 41 years (range 28-59), with a mean duration
      of a neuropathic bladder of 8 years (range 4-17 years) underwent evaluation for
      ileocystostomy urinary diversion. Indications for the procedure included a
      bladder capacity < or = 200 ml (10 patients), recurrent febrile urinary tract
      infection (nine patients), and urinary incontinence despite an indwelling
      urethral catheter (all eight women). Each was felt to be a poor candidate for, or
      refused, continent urinary diversion or bladder augmentation cystoplasty. All
      eight females required concomitant pubovaginal sling urethral compression to
      eliminate urinary leakage from a patulous, non-functional urethra. Two patients
      required bilateral ureteral reimplantation for grade III-IV/V reflux. Effective
      low-pressure urinary stomal drainage was achieved without the need for chronic
      catheterization in all of the patients with a mean duration of follow-up of 24
      months (range 6-60 months). No patient has developed pyelonephritis since the
      procedure. Urethral urinary leakage was eliminated in all of the female patients,
      whilst vesicoureteral reflux resolved in those with reflux preoperatively.

PMID- 8524607
TI  - Gastric volvulus--a complication of spinal cord omental transposition. Case
      report.

PMID- 8524608
TI  - Early cystic thoracic cord cavity complicating decompressive surgery for
      spondylotic spinal canal stenosis. Case report.
AB  - This is a report of a patient who developed thoracic cystic myelopathy
      immediately following an otherwise successful decompression operation for
      spondylotic stenosis secondary to osteophyte formation of the thoracic spinal
      canal. As this case shows, thoracic laminectomy is not without risks, and cystic
      myelopathy is a potential complication that should be borne in mind when surgery
      for spondylosis is being planned. Cavitation of the spinal cord may be associated
      with trauma secondary to extramedullary cord compression.

PMID- 8524609
TI  - Delayed neurological symptoms from the spontaneous migration of a bullet in the
      lumbosacral spinal canal. Case report.
AB  - In a patient wounded by a gunshot in the abdomen, the bullet was radiologically
      located intradurally at S1 level. Although she had no neurological deficit at
      admission, she developed pain and motor weakness a few days later. At operation
      the bullet was found at L4 level and its removal resulted in complete
      neurological recovery.

PMID- 8524610
TI  - Ossification of the lumbosacral dura and arachnoid following spinal cord trauma.
      Case report.
AB  - A case of progressive cauda equina syndrome secondary to ossification of the
      lumbosacral dura arachnoid following an incomplete spinal cord injury is
      presented. The etiology of the ossification is unclear and may be secondary to
      heterotopic osseous metaplasia such as occurs in other sites in spinal cord
      injured patients.

PMID- 8524611
TI  - [The dependence of egg-laying activity on the number of Leptopsylla segnis
      (Siphonaptera: Leptopsyllidae) fleas on the host].
AB  - The egg-laying activity in the fleas Leptopsylla segnis Schonherr declined when
      their number on the host (white mouse) was risen from 2-5 to 20. However, if the
      number of the parasites on host exceeded 30 the egg output per female increased.
      It is supposed, there is an density-dependent regulation of egg-laying activity
      in L. segnis, which operates in certain diapason of flea abundance. It appears
      that mechanism of this regulation is suppressed by heavy infestation.

PMID- 8524612
TI  - [The variability of the cestode perch parasite Proteocephalus percae in its
      host's geographic range].
AB  - Qualitative heterogeneity and its quantitative expression in geographically
      distant populations of Proteocephalus percae were studied. A wide spectrum of the
      possible values of the characters within which the expression of features is
      determined by environmental conditions, was detected.

PMID- 8524613
TI  - [The biorhythmology of primary and superinvasive opisthorchiasis. Seasonal
      changes in the circadian activity of the cyclic nucleotides and of the key enzyme
      of the pentosephosphate cycle (G-6-PD) in the peripheral blood of golden
      hamsters].
AB  - 570 males of golden hamsters were divided into 3 groups: I--free from invasion,
      II--once infected, III--repeatedly infected. Diurnal activity of cyclic
      nucleotides and enzyme of pentose-phosphate cycle (G-6-PhDG) was investigated in
      spring, autumn, and winter at 3, 7, 11 a.m. and 3, 7, 11 p.m. The golden hamsters
      once infected with opisthorchiasis do not show any seasonal changes in G-6-PhDG
      activity, but this invasion influences the total content of protein, diurnal
      oscillation of which depends upon seasons. In spring time the repeated invasion
      induces the diurnal rhythms of G-6-PhDG and of total protein content. Diurnal
      stereotype of cyclic nucleotides (cGMP, cAMP) demonstrates the dependence upon
      seasons and invasion frequency without any changes of the average diurnal level.

PMID- 8524614
TI  - [The interrelationships of ixodid ticks (Ixodidae) with the causative agents of
      transmissible vertebrate infections].
AB  - The ixodid ticks are the vectors of several hundreds of agents of transmission
      diseases of vertebrates and human. This agents are represented by viruses,
      rickettsiae, bacteria, protozoans and filariae. For the majority of these agents
      the ticks are not only vectors, but also are intermediate or final hosts. In the
      system agent-tick the antagonistic relationships dominate, and therefore the
      agent is actually a parasite of its vector. A wide spectrum of parasitic
      relationships form the high pathogenicity and lethality of an agent for its
      vector to the fast and complete elimination of a microorganism in a tick could be
      observed within the system in question. Somewhat balanced type of relationships
      occurs most often, thus pathogen agent causes a minimal damage to the tick
      vectors and could stay in their organism and hold a capability of the
      transmission to the vertebrate hosts and within the population of ticks.

PMID- 8524615
TI  - [The frequency of generalized infection in adult fasting ticks of the genus
      Ixodes in foci of borreliosis in Russia and the USA].
AB  - A total of 740 adult Ixodes persulcatus ticks were collected from the vegetation
      by flagging in Russian foci where Borrelia afzelii and B. garinii circulate, and
      156 I. dammini ticks were collected in northwestern USA regions in foci with B.
      burgdorferi s.str. circulation. Smears prepared from the internal organs of ticks
      were stained according to Romanovsky-Giemsa and analyzed under a microscope at a
      x 1125 magnification. All borreliae in 250 microscopic fields were counted, and
      concentration of microbial bodies per 100 microscopic fields was determined. The
      general level of infection by Borrelia in both vectors was similar: 26.2 x 3.2 in
      I. persulcatus and 26.3 +/- 7 in I. dammini. However, the proportions of ticks
      with generalized infections differ considerably (12.9 +/- 4.8 in I. persulcatus
      compared with 2.4 +/- 4.8 in I. dammini; significance of difference t = 3.1). We
      did not reveal any definite increase in the proportion of ticks with borreliae in
      the salivary glands among ticks with high concentrations of microbial bodies in
      the gut. In 25 I. persulcatus ticks with generalized infections, series of actual
      numbers of borreliae (per 100 microscopic fields) found in the gut and salivary
      glands did not correlate with one another (r = -0.23). These results confirm our
      previous conclusion (Korenberg, 1994) that frequencies of generalized infection
      in main vectors of different ixodid tick-borne borrelioses are also different,
      which is probably due to peculiarities of relationships between spirochetes of
      each species and corresponding tick vectors. These factors can be responsible for
      differences in the ways of horizontal and vertical transmission of pathogens
      belonging to the group under study.

PMID- 8524616
TI  - [The topographic selectivity of the landing and feeding by sucking of gadflies
      (Diptera: Tabanidae) in attacking cattle].
AB  - The detailed maps of the distribution of sittings and feedings of the 12 tabanid
      species among 22 zones of a cow's body are given. The material on the
      observations of individually marked tabanids attacking a single cow in conditions
      of the Pskov region in 1984-1990 (Konstantinov, 1992) has been used in present
      paper. It is established, that the distribution of sittings and feedings onto the
      cow's body has a species-specific character. The 12 species were arranged into 5
      groups based on characters of the topographical similarity of their
      distributions. The distribution of feedings has the less range than the
      distribution of sittings within each species. The distribution of sittings and
      feedings within each species coincide average by 60%. The effectiveness of
      tabanid's sittings is different within different zones of the cow's body.

PMID- 8524617
TI  - [The reproductive structure of groupings of the parasitic nematode Camallanus
      truncatus and the factors determining its alteration].
AB  - The reproductive structure of the nematode Camallanus truncatus in the population
      of the perch Perca fluviatilis in dependence upon host's size and seasons was
      studied. It is recovered, that only the bigger sized host groups influence the
      formation of reproductive-functional structure of the C. truncatus
      hemipopulation.

PMID- 8524618
TI  - The development and dissemination of non-patentable therapies (NPTs).

PMID- 8524619
TI  - Tuberculosis: why "the white plague"?

PMID- 8524620
TI  - Is immortality a possibility? A thought experiment concerning the inevitability
      of senescence due to endogenous parasitism.

PMID- 8524621
TI  - Euthanasia and the good life.

PMID- 8524622
TI  - Psychiatric illnesses, as well as other diseases, are not solely physical ot
      organic conditions, but are intertwined with thoughts, feelings, and
      interpersonal factors.

PMID- 8524623
TI  - Changing patterns of communicable disease: who is turning the kaleidoscope?

PMID- 8524624
TI  - Hypothesis: vascular compromise is the central pathogenic mechanism for acute
      hemorrhagic pancreatitis.

PMID- 8524625
TI  - Aspects of our present understanding of ischemic heart disease: more answers than
      questions.

PMID- 8524626
TI  - Stephen Rothman, pioneer of investigative dermatology.

PMID- 8524627
TI  - [Theme: bone marrow transplantation. Introduction and future outlook].

PMID- 8524628
TI  - [Allogeneic transplantation of stem cells--procedure and biological aspects].
AB  - The biological challenges to be overcome for allogeneic stem cell transplantation
      to succeed include: 1, eradication of the patient's malignant tissue by
      effective, yet tolerable cytoreductive preconditioning; 2, suppression of the
      patient's immunocompetence to prevent graft rejection; 3, a stem cell graft of
      adequate haematopoietic capacity must be obtained from a donor of acceptable
      histocompatibility, and transferred to the patient; and 4, since the graft also
      contains lymphocytes mediating antirecipient donor alloimmunity, posttransplant
      immunosuppressive therapy is required to prevent, and sometimes to treat graft
      versus-host disease. Basic immunobiological and clinical aspects, and methods
      used in stem cell transplantation are reviewed in the article.

PMID- 8524629
TI  - [Stem cell transplantation--more than bone marrow transplantation].
AB  - Allogeneic transplantation of peripheral blood haematopoietic stem cells is
      gradually becoming an alternative to bone marrow transplantation (BMT), probably
      because of its convenience for the donor; i.e. the donor does not need to be
      hospitalised and there is less post-harvesting discomfort. Preliminary findings
      suggest that the two treatment modes do not differ in time to engraftment or the
      incidences of rejection and graft-versus-host disease. However, the effects of
      peripheral blood stem cell transplantation on long-term survival, duration of
      haematopoiesis, and clinical outcome in cases of unrelated donors with or without
      certain degrees of HLA mismatch remain to be established. Moreover,
      transplantation with umbilical cord blood, being rich in haematopoietic stem
      cells, is another alternative to BMT, particularly in small children.

PMID- 8524630
TI  - [Allogeneic bone marrow transplantation in malignant blood diseases].
AB  - Allogeneic bone marrow transplantation has an established role in the treatment
      of malignant blood diseases. For some disorders it is at the moment the only
      curative treatment. As the complication risks of this treatment increase with
      age, the upper age limit for allogeneic transplantation is usually 50 to 60
      years. The main indications are acute leukaemias, chronic myeloid leukaemia and
      myelodysplastic syndromes. Selected patients with chronic lymphatic leukaemia,
      multiple myeloma and lymphoma are also treated with allogeneic transplantation.
      The most common intensive conditioning regimen preceding the transplantation
      consists of total body irradiation and cyclophosphamide. The source of
      haematopoietic stem cells has routinely been bone marrow, but the number of
      transplantations with stem cells harvested from blood is rapidly increasing. The
      proportion of transplantations from unrelated donors is growing.
      Histocompatibility testing is becoming more precise, which is likely to improve
      the results of unrelated donor transplantations to the level achieved with
      sibling donor transplantations.

PMID- 8524631
TI  - [Registry of volunteer bone marrow donors].

PMID- 8524632
TI  - [Treatment of severe acquired aplastic anemia].
AB  - Severe acquired aplastic anaemia is associated with high morbidity and mortality
      despite improvement in the results obtained both with bone marrow transplantation
      and with immunosuppressive treatment. Early bone marrow transplantation is the
      treatment of choice for patients under 45 years of age, if the neutrophil
      granulocyte count is less than 0.2-0.5 x 10(9)/l and an HLA-identical sibling
      donor is available. Other patients should receive primary immunosuppression with
      antithymocyte globulin, cyclosporin and glucocorticoid in combination with
      granulocyte colony-stimulating factor. If they fail to respond after three
      months, and a donor is available, such patients may be treated with bone marrow
      transplantation. However, transplantation with marrow from donors other than HLA
      identical siblings is still at an experimental stage.

PMID- 8524633
TI  - [Bone marrow transplantation in primary immunodeficiency syndrome and in
      osteopetrosis].
AB  - The designation primary immunodeficiency embraces a multiplicity of diseases of
      which only the more severe constitute indications for BMT (bone marrow
      transplantation)--e.g. severe combined immunodeficiency (SCID), Wiskott-Aldrich
      syndrome, familial haemophagocytic lymphohistiocytosis and malignant
      osteopetrosis. In cases of immunodeficiency, the outcome of BMT is strongly
      dependent on the patient's age, clinical status at transplantation and the type
      of immunodeficiency. In children with SCID who undergo BMT during the first few
      months of life, lasting cures can be obtained in almost 100 percent of the cases,
      whereas there is only a 15 percent probability of success if the child is older,
      infected, cannot undergo cytostatic preconditioning or cannot be given T-cell
      depleted bone marrow.

PMID- 8524634
TI  - [Patient information and conditioning for allogeneic stem cell transplantation].
AB  - Allogeneic stem cell transplantation is a curative treatment alternative in
      selected patients with isolated life-threatening bone marrow disorders and
      certain congenital metabolic anomalies. The majority of patients have malignant
      blood disorders. The treatment is associated with risk of fatal or painful
      complications, both early and late in the course. As cytoreductive
      preconditioning has yet to be optimised, it is not always sufficient to eradicate
      the patient's malignant tissue. Moreover, it may give rise to serious, sometime
      fatal, extramedullary side effects. Patients must therefore be thoroughly
      informed of all aspects of the treatment and its alternatives, before it is
      undertaken. The indications must be restrictive and the evaluation of
      contraindications stringent to ensure that the risk is acceptable both to the
      patient and those responsible for treatment.

PMID- 8524635
TI  - [Infections following bone marrow transplantation].
AB  - Recent years have witnessed a reduction in the frequency of infectious
      complications both in allogeneic and in autologous bone marrow transplantation
      (BMT). With a frequency of 30-40 percent, septicaemia is the predominant problem
      during the aplastic phase. Owing to the introduction of prophylaxis with
      quinolones, there has been a shift in the aetiological spectrum toward Gram
      positive infections, and Gram-negative infections now account for less than 10
      percent of all cases. In turn, this has been accompanied by reduced mortality.
      Early institution of treatment based on viraemia diagnosis has radically reduced
      the substantial morbidity and mortality formerly due to cytomegalovirus infection
      during the first three months after BMT. Antibiotic prophylactic treatment for
      Pneumocystis carinii infection during the first year, and against pneumococcal
      infections thereafter, has also been highly successful. The remaining problems
      are the diagnosis and treatment of invasive fungal infections and the increased
      susceptibility to infection among those who develop graft-versus-host disease.

PMID- 8524636
TI  - [Principles of priorities in health care and predictive tests discussed at a
      Scandinavian ethics meeting].

PMID- 8524637
TI  - [General medicine in Scandinavian basic and continuing education. Learning for
      life--or living to learn].

PMID- 8524638
TI  - [Autologous cartilage cell transplantation. The goal is pain relief and restored
      joint function].
AB  - Chondral and osteochondral damage is a common result of trauma to the joints. The
      capacity of cartilage to heal such damage is poor, and repetitive wear on joint
      surfaces that do not heal results in impaired joint function, which can culminate
      in full blown arthrosis. Thus, it is important to improve our knowledge of
      cartilage regenerative potential, and develop methods to forestall progression to
      arthrosis by promoting the early healing of cartilage damage. Autologous
      cartilage cell transplantation may be a mean of healing cartilage damage. A
      method of cultivating autologous chondrocytes for transplantation in the
      treatment of isolated damage to articular cartilage of the knee is presented in
      the article.

PMID- 8524639
TI  - Structure of open promoter complexes with Escherichia coli RNA polymerase as
      revealed by the DNase I footprinting technique: compilation analysis.
AB  - Footprinting data for 33 open promoter complexes with Escherichia coli RNA
      polymerase, as well as 17 ternary complexes with different regulators, have been
      compiled using a computer program FUTPR. The typical and individual properties of
      their structural organization are analyzed. Promoters are subgrouped according to
      the extent of the polymerase contact area. A set of alternative sequence elements
      that could be responsible for RNA polymerase attachment in different promoter
      groups is suggested on the basis of their sequence homology near the
      hyperreactive sites. The model of alternative pathways used for promoter
      activation is discussed.

PMID- 8524640
TI  - The transcription factors ATF-1 and CREB-1 bind constitutively to the hypoxia
      inducible factor-1 (HIF-1) DNA recognition site.
AB  - The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding
      activity that specifically recognizes an 8 bp motif known to be essential for
      hypoxia-inducible erythropoietin gene transcription. Subsequently HIF-1 activity
      has also been found in cell lines which do not express erythropoietin, suggesting
      that HIF-1 is part of a widespread oxygen sensing mechanism. In electrophoretic
      mobility shift assays HIF-1 DNA binding activity is only detectable in nuclear
      extracts of cells cultivated in a low oxygen atmosphere. In addition to HIF-1, a
      constitutive DNA binding activity also specifically binds the HIF1 probe. Here we
      report that CRE and AP1 oligonucleotides efficiently competed for binding of the
      HIF1 probe to this constitutive factor, whereas HIF-1 activity itself remained
      unaffected. Monoclonal antibodies raised against the CRE binding factors ATF-1
      and CREB-1 supershifted the constitutive factors ATF-1 and CREB-1 supershifted
      the constitutive factor, while Jun and Fos family members, which constitute the
      AP-1 factor, were immunologically undetectable. Recombinant ATF-1 and CREB-1
      proteins bound HIF1 probes either as homodimers or as heterodimers, indicating a
      new binding specificity for ATF-1/CREB-1. Finally, reporter gene assays in HeLa
      cells treated with either a cAMP analogue or a phorbol ester suggest that the
      PKA, but not the PKC signalling pathway is involved in oxygen sensing.

PMID- 8524641
TI  - Evaluation of tyrosinase minigene co-injection as a marker for genetic
      manipulations in transgenic mice.
AB  - The utility of tyrosinase minigene co-injection was evaluated as a visual marker
      for the generation and breeding of transgenic mice. In an evaluation of 39
      transgenic founder animals and 44 transgenic lines five phenotypic patterns of
      pigmentation were consistently observed, including albino, dark, light, mottled
      and himalayan. In these studies co-injection of the tyrosinase minigene along
      with the transgene of interest (TOI) resulted in genomic integration of the two
      transgenes in 95% of the F0 generation. Co-segregation of transgenes occurred in
      94% of doubly transgenic mice in the F1 generation, without dissociation in
      subsequent generations. All pigmented phenotypes proved useful for distinguishing
      homozygous from heterozygous F2 animals via backcross trials, while the light,
      mottled and himalayan phenotypes proved useful in visually discriminating between
      homozygous and heterozygous F2 animals. In addition, the light, mottled and
      himalayan phenotypes proved useful in determining segregation patterns of
      transgenes in the progeny of crosses between separate transgenic lines. Moreover,
      there appears to be a correlation between intensity of pigmentation and degree of
      expression of the co-injected TOI. These studies confirm that tyrosinase co
      injection is a useful adjunct in transgenic mouse studies and can serve to reduce
      routine genetic validation of transgenic lines.

PMID- 8524642
TI  - The amino-terminal tails of the core histones and the translational position of
      the TATA box determine TBP/TFIIA association with nucleosomal DNA.
AB  - We establish that the TATA binding protein (TBP) in the presence of TFIIA
      recognizes the TATA box in nucleosomal DNA dependent on the dissociation of the
      amino-terminal tails of the core histones from the nucleosome and the position of
      the TATA box within the nucleosome. We examine TBP/TFIIA access to the TATA box
      with this sequence placed in four distinct rotational frames with reference to
      the histone surface and at three distinct translational positions at the edge,
      side and dyad axis of the nucleosome. Under our experimental conditions, we find
      that the preferential translational position at which TBP/TFIIA can bind the TATA
      box is within linker DNA at the edge of the nucleosome and that binding is
      facilitated if contacts made by the amino-terminal tails of the histones with
      nucleosomal DNA are eliminated. TBP/TFIIA binding to DNA at the edge of the
      nucleosome occurs with the TATA box in all four rotational positions. This is
      indicative of TBP/TFIIA association directing the dissociation of the TATA box
      from the surface of the histone octamer.

PMID- 8524643
TI  - CCAAT-box binding protein NF-Y (CBF, CP1) recognizes the minor groove and
      distorts DNA.
AB  - The CCAAT box is one of the most common promoter elements. The evolutionarily
      conserved heteromeric factor NF-Y binds this sequence with high affinity and
      specificity. By comparing the methylation interference patterns of different
      sites, performing electrophoretic mobility shift assays (EMSA) with IC
      substituted oligonucleotides and competition experiments with the minor groove
      binding (MGB) drugs distamicin A, tallimustine and Hoechst 33258 we show that NF
      Y makes key minor groove interactions. Circular permutation assays on four CCAAT
      boxes, MHC Class II Ea, HSP70, epsilon-globin and MSV, indicate that NF-Y is able
      to distort the double helix by angles of 62-82 degrees, depending on the site
      used, and suggest that nucleotides flanking the CCAAT pentanucleotide influence
      the degree of bending.

PMID- 8524644
TI  - Taq52 I, a novel and thermostable type II restriction endonuclease from the genus
      Thermus, recognising the pentanucleotide sequence GC(A or T)GC and cleaving DNA
      between the first and second bases of the recognition sequence: G decreased or
      reduced C(A or T)GC.
AB  - 127 isolates of the genus Thermus, from neutral and alkaline hot water springs on
      four continents, have been screened for the presence of restriction endonuclease
      activity. An isolate (YS52) from Yellowstone National Park, USA, showed a high
      level of restriction endonuclease activity when a cell free extract was incubated
      with lambda phage DNA at 65 degrees C. A Type II restriction endonuclease (Taq52
      I) has been partially purified from this isolate and the recognition and cleavage
      site determined. Taq52 I has a novel interrupted palindromic tetranucleotide
      recognition sequence GCWGC, where W can be either adenine (A) or thymine (T). It
      hydrolyses the phosphodiester bond in both strands of the substrate between the
      first and second bases of the recognition sequence: 5'G decreased or reduced
      CWGC3', producing three-base 5'-OH overhangs (sticky ends). The enzyme has a pH
      optimum of 7.0, requires 8 mM MgCl2 for maximum activity and is thermally stable,
      retaining full enzyme activity following incubation at 79 degrees C for 10 min.
      Taq52 I not only represents a new addition to the Type II restriction
      endonucleases, but also increases the small list of thermostable restriction
      endonucleases.

PMID- 8524645
TI  - A comparison of the hairpin stability of the palindromic d(CGCG(A/T)4CGCG)
      oligonucleotides.
AB  - The palindromic deoxyribonucleotides 5'-CGCGA-TATCGCG-3' and 5'-CGCGTTAACGCG-3'
      have been characterized by 1H NMR spectroscopy. The NMR data identified both B
      DNA duplex conformations and hairpin conformations, the latter with loop regions
      consisting of the four central nucleotides. The resonances of the various
      conformations were assigned by use of two-dimensional NMR methods. The relative
      stability of the various conformations was investigated as a function of
      temperature, ionic strength and nucleotide concentration. The duplexes were found
      to be stabilized at high ionic strength and at low temperature, while the
      hairpins were stabilized at low ionic strength and at medium temperature. The
      thermodynamics of the duplex-hairpin and the hairpin-random coil transitions were
      examined, and compared to the other two oligonucleotide in the palindromic
      d(CGCG(A/T)4CGCG) oligonucleotide family. The relative stabilities of the duplex
      conformations with respect to the random coil conformations are similar for the
      d(CGCGAATTCGCG), d(CGCGATATCGCG) and d(CGCGTATACGCG) oligonucleotides. The duplex
      conformation of d(CGCGTTAACGCG) is less stable. The hairpin of d(CGCGTTAACGCG)
      seems also to be less stable relative to the random coil conformation than in the
      case of the other oligonucleotides at an equal oligonucleotide concentration. A
      cruciform intermediate between the duplex and hairpin conformations is suggested
      to explain some discrepancies observed in this work in case of the
      d(CGCGTTAACGCG) oligonucleotide. This is similar to what has been reported for
      the d(CGCGTATACGCG) oligonucleotide.

PMID- 8524646
TI  - HMG box 4 is the principal determinant of species specificity in the RNA
      polymerase I transcription factor UBF.
AB  - Transcription of ribosomal genes requires, in addition to RNA polymerase I, the
      trans-acting factors UBF and Rib1 in Xenopus or SL1 in humans. RNA polymerase I
      transcription is remarkably species specific. Between closely related species SL1
      is the sole determinant of this specificity. Between more distantly related
      species, however, UBF is also a component of this species specificity. Xenopus
      UBF cannot function in human RNA polymerase I transcription and human UBF cannot
      function in Xenopus RNA polymerase I transcription. Xenopus and human UBFs are
      remarkably similar at the amino acid sequence level, both containing multiple HMG
      box DNA binding motifs. The only major difference between xUBF and hUBF is the
      lack of a HMG box 4 equivalent in xUBF. Utilizing a series of hybrid UBF
      molecules we have identified HMG box 4 as the principal determinant of species
      specificity. Addition of human HMG box 4 to xUBF converts it to a form that
      functions in human RNA polymerase I transcription. Deletion of HMG box 4 from
      hUBF converts it to a form that functions in Xenopus RNA polymerase I
      transcription. Furthermore, mutations within Xenopus UBF demonstrate that UBF
      requires a precise arrangement and number of HMG boxes to function in RNA
      polymerase I transcription.

PMID- 8524647
TI  - Cysteine tRNAs of plant origin as novel UGA suppressors.
AB  - We have isolated and sequenced chloroplast (chl) and cytoplasmic (cyt) cysteine
      tRNAs from Nicotiana rustica. Both tRNAs carry a GCA anticodon but beyond that
      differ considerably in their nucleotide sequences. One obvious distinction
      resides in the presence of N6-isopentenyladenosine (i6A) and 1-methylguanosine
      (m1G) at position 37 in chl and cyt tRNA(Cys) respectively. In order to study the
      potential suppressor activity of tRNAs(Cys) we used in vitro synthesized zein
      mRNA transcripts in which an internal UGA stop codon had been placed in either
      the tobacco rattle virus (TRV)- or tobacco mosaic virus (TMV)-specific codon
      context. In vitro translation was carried out in a messenger- and tRNA-dependent
      wheat germ extract. Both tRNA(Cys) isoacceptors stimulate read-through over the
      UGA stop codon, however, chl tRNA(GCA)Cys is more efficient than the cytoplasmic
      counterpart. The UGA in the two viral codon contexts is suppressed to about the
      same extent by either of the two tRNAs(Cys), whereas UGA in the beta-globin
      context is not recognized at all. The interaction of tRNA(GCA)Cys with UGA
      requires an unconventional G:A base pair in the wobble position, as postulated
      earlier for plant tRNA(G psi A)Tyr misreading the UAA stop codon. This is the
      first case that a cysteine-accepting tRNA has been characterized as a natural UGA
      suppressor.

PMID- 8524648
TI  - Footprinting of tRNA(Phe) transcripts from Thermus thermophilus HB8 with the
      homologous phenylalanyl-tRNA synthetase reveals a novel mode of interaction.
AB  - The phosphates of the tRNA(Phe) transcript from Thermus thermophilus interacting
      with the cognate synthetase were determined by footprinting. Backbone bond
      protection against cleavage by iodine of the phosphorothioate-containing
      transcripts was found in the anticodon stem-loop, the D stem-loop and the
      acceptor stem and weak protection was also seen in the variable loop. Most of the
      protected phosphates correspond to regions around known identity elements of
      tRNA(Phe). Enhancement of cleavage at certain positions indicates bending of
      tRNAPhe upon binding to the enzyme. When applied to the three-dimensional model
      of tRNA(Phe) from yeast the majority of the protections occur on the D loop side
      of the molecule, revealing that phenylalanyl-tRNA synthetase has a rather complex
      and novel pattern of interaction with tRNAPhe, differing from that of other known
      class II aminoacyl-tRNA synthetases.

PMID- 8524649
TI  - A monoclonal antibody extends the half-life of an anti-HIV oligodeoxynucleotide
      and targets it to CD4+ cells.
AB  - An approach was sought to increase the half-life and target cell specificity of
      antisense oligodeoxynucleotides (oligos). A monoclonal antibody (MAb) was derived
      from mice immunised with an oligo complementary to a region (1-20) of the HIV
      genome. This MAb exerts a protective effect on the oligo from the degradation
      induced by plasma exonucleases in vitro and in vivo. Moreover the anti-oligo MAb
      dissociates from the oligo in the presence of its complementary sequence to allow
      hybridization of the two complementary strands. To direct the oligo to CD4+ cells
      the anti-oligo MAb was cross-linked to an anti-CD4 MAb. The heteroaggregate
      determines a 5-fold increase in the cellular membrane binding of the oligo to
      CD4+ lymphocytes. These findings suggest a new approach to enhancing the
      therapeutic action and the target specificity of antisense oligodeoxynucleotides
      useful for the selective inhibition of HIV replication in vivo.

PMID- 8524650
TI  - Synthesis of cysteine-containing dipeptides by aminoacyl-tRNA synthetases.
AB  - Arginyl-tRNA synthetase (ArgRS) catalyses AMP- and PPi-independent deacylation of
      Arg-tRNAArg in the presence of cysteine. A dipeptide, Arg-Cys, is a product of
      this deacylation reaction. Similar reaction with homocysteine yields Arg-Hcy.
      Arginine is a noncompetitive inhibitor of the cysteine-dependent deacylation
      which indicates that cysteine binds to the enzyme-Arg-tRNAArg complex at a site
      separate from the arginine binding site. In the presence of arginine, [14C]Arg
      tRNAArg is deacylated at a rate similar to the rate of its spontaneous
      deacylation in solution and [14C]arginine is a product. Experiments with cysteine
      derivatives indicate that the -SH group is essential for the reaction whereas 
      NH2 and -COOH groups are not. Thioesters of arginine are formed with 3
      mercaptopropionic acid, N-acetyl-L-cysteine and dithiothreitol. These data
      suggest that formation of the dipeptide Arg-Cys involves a thioester
      intermediate, S-(L-arginyl)-L-cysteine, which is not observed because of the
      rapid rearrangement to form a stable peptide bond. Facile intramolecular reaction
      results from the favorable geometric arrangement of the alpha-amino group of
      cysteine with respect to the thioester formed in the initial reaction. Similar
      reactions, yielding Ile-Cys and Val-Cys, are catalyzed by isoleucyl- and valyl
      tRNA synthetases, respectively.

PMID- 8524651
TI  - Cloning and characterisation of the gene encoding the ribosomal protein S5 (also
      known as rp14, S2, YS8) of Saccharomyces cerevisiae.
AB  - The protein sequence derived from a cloned yeast gene and partial cDNA has high
      sequence identity to 40S ribosomal subunit S5 proteins of higher eukaryotic
      origin. The open reading frame of the gene is flanked by consensus sequence
      motifs characteristic of ribosomal protein genes and the pattern of transcription
      of the gene in yeast cells subjected to nutritional shift or temperature shock is
      also typical of a ribosomal protein gene. The gene is single copy and essential
      for viability. The predicted sequence of the N-terminus of the protein identifies
      it as a phosphorylated ribosomal protein variously known as rp14, S2 or YS8, the
      least basic of the non-acidic ribosomal proteins of Saccharomyces cerevisiae.

PMID- 8524652
TI  - DNA strand transfer catalyzed by the 5'-3' exonuclease domain of Escherichia coli
      DNA polymerase I.
AB  - A protein which promotes DNA strand transfer between linear double-stranded
      M13mp19 DNA and single-stranded viral M13mp19 DNA has been isolated from recA-
      E.coli. The protein is DNA polymerase I. Strand transfer activity residues in the
      small fragment encoding the 5'-3' exonuclease and can be detected using a
      recombinant protein comprising the first 324 amino acids encoded by polA. Either
      the recombinant 5'-3' exonuclease or intact DNA polymerase I can catalyze joint
      molecule formation, in reactions requiring only Mg2+ and homologous DNA
      substrates. Both kinds of reactions are unaffected by added ATP. Electron
      microscopy shows that the joint molecules formed in these reactions bear
      displaced single strands and therefore this reaction is not simply promoted by
      annealing of exonuclease-gapped molecules. The pairing reaction is also polar and
      displaces the 5'-end of the non-complementary strand, extending the heteroduplex
      joint in a 5'-3' direction relative to the displaced strand. Thus strand transfer
      occurs with the same polarity as nick translation. These results show that
      E.coli, like many eukaryotes, possesses a protein which can promote ATP
      independent strand-transfer reactions and raises questions concerning the
      possible biological role of this function.

PMID- 8524653
TI  - R4, a non-LTR retrotransposon specific to the large subunit rRNA genes of
      nematodes.
AB  - A 4.7 kb sequence-specific insertion in the 26S ribosomal RNA gene of Ascaris
      lumbricoides, named R4, is shown to be a non-long terminal repeat (non-LTR)
      retrotransposable element. The R4 element inserts at a site in the large subunit
      rRNA gene which is midway between two other sequence-specific non-LTR
      retrotransposable elements, R1 and R2, found in most insect species. Based on the
      structure of its open reading frame and the sequence of its reverse transcriptase
      domain, R4 elements do not appear to be a family of R1 or R2 elements that have
      changed their insertion site. R4 is most similar in structure and in sequence to
      the element Dong, which is not specialized for insertion into rRNA units. Thus R4
      represents a separate non-LTR retrotransposable element that has become
      specialized for insertion in the rRNA genes of its host. Using oligonucleotide
      primers directed to a conserved region of the reverse transcriptase encoding
      domain, insertions in the R4 site were also amplified from Parascaris equorum and
      Haemonchus contortus. Why several non-LTR retrotransposable elements have become
      specialized for insertion into a short (87 bp) region of the large subunit rRNA
      gene is discussed.

PMID- 8524654
TI  - The ribosomal neighbourhood of the central fold of tRNA: cross-links from
      position 47 of tRNA located at the A, P or E site.
AB  - The naturally occurring nucleotide 3-(3-amino-3-carboxy-propyl)uridine (acp3U) at
      position 47 of tRNA(Phe) from Escherichia coli was modified with a diazirine
      derivative and bound to ribosomes in the presence of suitable mRNA analogues
      under conditions specific for the ribosomal A, P or E sites. After photo
      activation at 350 nm the cross-links to ribosomal proteins and RNA were
      identified by our standard procedures. In the 30S subunit protein S19 (and weakly
      S9 and S13) was the target of cross-linking from tRNA at the A site, S7, S9 and
      S13 from the P site and S7 from the E site. Similarly, in the 50S subunit L16 and
      L27 were cross-linked from the A site, L1, L5, L16, L27 and L33 from the P site
      and L1 and L33 from the E site. Corresponding cross-links to rRNA were localized
      by RNase H digestion to the following areas: in 16S rRNA between positions 687
      and 727 from the P and E sites, positions 1318 and 1350 (P site) and 1350 and
      1387 (E site); in the 23S rRNA between positions 865 and 910 from the A site,
      1845 and 1892 (P site), 1892 and 1945 (A site), 2282 and 2358 (P site), 2242 and
      2461 (P and E sites), 2461 and 2488 (A site), 2488 and 2539 (all three sites) and
      2572 and 2603 (A and P sites). In most (but not all) cases, more precise
      localizations of the cross-link sites could be made by primer extension analysis.

PMID- 8524655
TI  - The effects of the ring fragmentation product of thymidine C5-hydrate on
      phosphodiesterases and klenow (exo-) fragment.
AB  - N-(2-Deoxy-beta-D-erythro-pentofuranosyl)-N-3-(2R-hydroxyisobutyric acid)urea
      (alpha-R-hydroxy-beta-ureidoisobutyric acid, 8) was site specifically
      incorporated into a series of oligonucleotides via the ammonolysis of biopolymers
      containing 5R-thymidine C5-hydrate (3). alpha-R-hydroxy-beta-ureidoisobutyric
      acid (8) inhibits snake venom phosphodiesterase, lambda exonuclease and Klenow
      (exo-) fragment. Kinetic measurements for insertion of nucleotides opposite 8 by
      Klenow (exo-) fragment indicate that this lesion is instructive.

PMID- 8524656
TI  - Regulation of mouse thymidylate synthase gene expression in growth-stimulated
      cells: upstream S phase control elements are indistinguishable from the essential
      promoter elements.
AB  - Expression of the mammalian thymidylate synthase (TS) gene in growth-stimulated
      cells is closely coordinated with entry into S phase. Previous studies with
      transfected TS minigenes have shown that sequences upstream of the coding region
      as well as an intron in the transcribed region are both necessary for proper
      regulation of TS mRNA content in growth-stimulated cells. The goal of the present
      study was to identify the upstream regulatory elements. Minigenes consisting of
      TS 5' flanking sequences linked to the TS coding region (interrupted by introns 1
      and 2) were stably transfected into mouse 3T6 cells. Deletion and site-directed
      mutagenesis of the 5' flanking region revealed that there is a close
      correspondence between the upstream sequences that are necessary for S phase
      regulation and the 30 nucleotide region that is essential for promoter activity.
      These observations raised the possibility that regulation of the TS gene occurs
      at the transcriptional level. However, nuclear run-on assays showed that the rate
      of transcription of the TS gene changed very little during the G1-S phase
      transition. Furthermore, when the TS promoter was linked to an intron-less
      luciferase indicator gene, there was no change in expression following growth
      stimulation. Therefore it appears that the TS gene is controlled primarily at the
      posttranscriptional level, and that the TS essential promoter region is necessary
      (although not sufficient) for proper S phase regulation.

PMID- 8524657
TI  - Non-radioactive detection of oligonucleotide probes by photochemical
      amplification of dioxetanes.
AB  - We describe a new method of non-radioactive labelling and detection of
      oligonucleotide probes. The approach is based on a simple chemical principle.
      Oligonucleotides labelled with methylene blue (a photosensitizer) are hybridized
      on a membrane to immobilized DNA target sequences. After hybridization and
      stringency washing 2(-)[3-(hydroxyphenyl)methoxymethylene] adamantane is added to
      the membrane and the membrane is irradiated with a tungsten lamp light source
      through a cut-off filter. Thermally stable dioxetanes are amplified during
      irradiation at the positions of the labelled probe. These amplified dioxetanes
      are detected using chemically triggered chemiluminescent decay. Signals are
      recorded on commercial X-ray film. Detection is possible immediately after the
      last washing step and a hard copy of the blot is obtained within 1 h. Dependent
      on the level of the target sequences, the sensitivity of the method allows
      detection of 0.3 pg single-stranded M13mp18(+) plasmid DNA in dot blots and 75 pg
      in Southern blots. Additional immunological reaction steps and washing steps with
      blocking reagents and buffers are avoided. Furthermore, expensive reagents and
      equipment for physical detection are not necessary. The method might be
      particularly useful for fast routine analysis in forensic and medical
      applications. The synthesis of the olefin, conditions of hybridization and the
      protocol of detection are described in detail.

PMID- 8524658
TI  - Molecular cloning of cDNA encoding the Xenopus homolog of mammalian RelB.
AB  - We have molecularly cloned cDNA encoding a new Rel-related protein in Xenopus
      laevis. Nucleotide sequencing revealed that the product is most homologous to
      mammalian RelB in its N-terminal region. Furthermore, the putative protein kinase
      A phosphorylation site (RRPS), found in most of the Rel family proteins, but
      replaced by QRLT in mammalian RelB, is replaced by QRIT, indicating that our cDNA
      most likely encodes the Xenopus homolog of mammalian RelB (XrelB). As in the case
      of mouse RelB, XrelB alone does not bind to DNA efficiently, while XrelB/human
      p50 heterodimers bind to kappa B sites and activate transcription. XrelB
      transcripts are present at all stages of oocyte maturation and in adult tissues
      examined. However, in staged embryos XrelB is undetectable from neurula to stage
      28 and resumes expression at stage 47, while Xrel1/XrelA, the Xenopus homolog of
      p65, has been demonstrated to be expressed throughout embryogenesis. These
      results raise the possibility that XrelB and Xrel1/XrelA play different roles in
      the development of X.laevis.

PMID- 8524659
TI  - The Xenopus intron-encoded U17 snoRNA is produced by exonucleolytic processing of
      its precursor in oocytes.
AB  - U17 is a small nucleolar RNA encoded in the introns of the Xenopus laevis gene
      for ribosomal protein S7 (formerly S8, see Note). To study the mechanisms
      involved in its in vivo processing from S7 transcripts, various in vitro
      synthesized RNAs embedding a U17 sequence have been microinjected into the
      germinal vesicle of Xenopus oocytes and their processing analysed. In particular,
      the Xenopus U17 gene copies a and f and a U17 gene copy from the pufferfish Fugu
      rubripes have been used. Information about the nature of the processing
      activities involved in U17 RNA maturation have been sought by injecting
      transcripts protected from exonucleolytic attack at their 5'-end by capping
      and/or lengthened at their 3'-end by polyadenylation. The results obtained
      indicate that U17 RNA processing is a splicing-independent event and that it is
      mostly or entirely due to exonucleolytic degradation at both the 5'- and 3'-ends
      of the precursor molecules. Moreover, it is concluded that the enzymes involved
      are of the processive type. It is suggested that the apparatus for U17 RNA
      processing is that responsible for the degradation of all excised and debranched
      introns. Protection from exonucleolytic attack, due to the tight structure and/or
      to the binding of specific proteins, would be the mechanism by which U17 RNA is
      produced.

PMID- 8524660
TI  - The synthesis of blocked triplet-phosphoramidites and their use in mutagenesis.
AB  - A general approach for the synthesis of oligonucleotide-triplet phosphoramidites
      and the synthesis of four such blocks are described. A strategy was devised to
      minimize the number of dimer precursors needed for synthesis of a complete set of
      triplet-amidite blocks encoding all 20 amino acids. Whereas synthesis of 20
      triplet-amidite blocks consisting of codon sequences requires 16 dimer blocks,
      just seven dimer blocks are required to synthesize all required antisense
      sequences. The antisense sequences are then converted to codons in template
      mediated replication. Using a mixture of four triplet-amidites and conventional
      automated solid-phase DNA synthesis, short (6mer) and medium length (30mer)
      oligonucleotide mixtures were synthesized and analyzed. The latter was replicated
      in vitro and used as a mutagenic cassette to produce four mutants of Asp 221 in
      the enzyme thymidylate synthase. The method establishes the direction and utility
      for the production and use of triplet-amidite blocks in DNA synthesis.

PMID- 8524661
TI  - Identification of a very early promoter of insect Hz-1 virus using a novel dual
      expression shuttle vector.
AB  - Very early promoters of viruses control the proper cascade expression of viral
      genes and are essential for completion of virus life cycles. These promoters are
      usually rare and weak and do not encode structural proteins. As a result, they
      are difficult to identify. In order to identify and clone the very early
      promoters of a large eukaryotic DNA virus, the Hz-1 virus, a novel cloning
      strategy was applied. This strategy is based on a dual-expression shuttle vector
      containing a promoter-less lacZ gene. Insertion of eukaryotic promoters upstream
      permits the efficient expression of LacZ in bacteria cells. The function of the
      putative promoters was then confirmed by their proper expression in insect cells.
      The first two productive infection-specific promoters of Hz-1 virus, contained
      within the shuttle vectors pTSV-2-129 and pTSV-2-49, were cloned from the HindIII
      K and HindIII-A fragments of the Hz-1 viral genome, respectively. By primer
      extension analysis, an immediate and constitutive expression of the promoter in
      clone pTSV-2-129 was detected after viral infection. Identification of the
      productive infection-specific promoters has laid down important groundwork for
      future studies on the molecular mechanism of the transcriptional switch between
      productive and persistent infections of Hz-1 virus.

PMID- 8524662
TI  - Transcription termination at the Escherichia coli thra terminator by spinach
      chloroplast RNA polymerase in vitro is influenced by downstream DNA sequences.
AB  - We have investigated the mechanism of transcription termination in vitro by
      spinach chloroplast RNA polymerase using templates encoding variants of the
      transcription-termination structure (attenuator) of the regulatory region of the
      threonine (thr) operon of Escherichia coli. Fourteen sequence variants located
      within its d(G+C) stem-loop and d(A+T)-rich regions were studied. We found that
      the helix integrity in the stem-loop structure is necessary for termination but
      that its stability is not directly correlated with termination efficiency. The
      sequence of the G+C stem-loop itself also influences termination. Moreover, the
      dA template stretch at the 3' end of the terminator plays a major role in
      termination efficiency, but base pairing between the A and U tract of the
      transcript does not. From the studies using deletion variants and a series of
      mutants that alter the sequences immediately downstream from the transcription
      termination site, we found that termination of transcription by spinach
      chloroplast RNA polymerase was also modulated by downstream DNA sequences in a
      sequence-specific manner. The second base immediately following the poly(T) tract
      is crucial for determining the termination efficiency by chloroplast RNA
      polymerase, but not of the T7 or E.coli enzymes.

PMID- 8524663
TI  - The ETS-domain transcription factors Elk-1 and SAP-1 exhibit differential DNA
      binding specificities.
AB  - The ETS DNA-binding domain is conserved amongst many eukaryotic transcription
      factors. ETS-domains bind differentially to specific DNA sites containing a
      central GGA trinucleotide motif. The nucleotides flanking this motif define the
      binding specificity of individual proteins. In this study we have investigated
      binding specificity of the ETS-domains from two members of the ternary complex
      factor (TCF) subfamily, Elk-1 and SAP-1. The ETS DNA-binding domains of Elk-1
      (Elk-93) and SAP-1 (SAP-92) select similar sites from random pools of double
      stranded oligonucleotides based on the consensus sequence ACCGGAAGTR. However,
      SAP-92 shows a more relaxed binding site selectivity and binds efficiently to a
      greater spectrum of sites than does Elk-93. This more relaxed DNA binding site
      selectivity is most pronounced in nucleotides located on the 3' side of the GGA
      motif. This differential DNA-binding specificity is also exhibited by longer TCF
      derivatives and, indeed by the full-length proteins. Our results suggest that the
      range of potential in vivo target sites for SAP-1 is likely to be greater than
      for Elk-1. We discuss our results in relation to other similar studies carried
      out with more divergent ETS-domains.

PMID- 8524664
TI  - Consistencies of individual DNA base-amino acid interactions in structures and
      sequences.
AB  - Amino acid-amino acid interaction energies have been derived from crystal
      structure data for a number of years. Here is reported the first derivation of
      normalized relative interaction from binding data for each of the four bases
      interacting with a specific amino acid, utilizing data from combinatorial
      multiplex DNA binding of zinc finger domains [Desjarlais, J. R. and Berg, J. M.
      (1994) Proc. Natl. Acad. Sci. USA, 91, 11099-11103]. The five strongest
      interactions are observed for lysine-guanine, lysine-thymine, arginine-guanine,
      aspartic acid-cytosine and asparagine-adenine. These rankings for interactions
      with the four bases appear to be related to base-amino acid partial charges.
      Also, similar normalized relative interaction energies are derived by using DNA
      binding data for Cro and lambda repressors and the R2R3 c-Myb protein domain
      [Takeda, Y., Sarai, A. and Rivera, V. M. (1989) Proc. Natl. Acad. Sci. USA, 86,
      439-443; Sarai, A. and Takeda, Y. (1989) Proc. Natl. Acad. Sci. USA, 86, 6513
      6517; Ogata, K. et al. (1995) submitted]. These energies correlate well with the
      combinatorial multiplex energies, and the strongest cases are similar between the
      two sets. They also correlate well with similar relative interaction energies
      derived directly from frequencies of bases in the bacteriophage lambda operator
      sequences. These results suggest that such potentials are general and that
      extensive combinatorial binding studies can be used to derive potential energies
      for DNA-protein interactions.

PMID- 8524665
TI  - 5' contexts of Escherichia coli and human termination codons are similar.
AB  - The nearest 5' context of 2559 human stop codons was analysed in comparison with
      the same context of stop-like codons (UGG, UGC, UGU, CGA for UGA; CAA, UAU, UAC
      for UAA; and UGG, UAU, UAC, CAG for UAG). The non-random distribution of some
      nucleotides upstream of the stop codons was observed. For instance, uridine is
      over-represented in position -3 upstream of UAG. Several codons were shown to be
      over-represented immediately upstream of the stop codons: UUU(Phe), AGC(Ser), and
      the Lys and Ala codon families before UGA; AAG(Lys), GCG(Ala), and the Ser and
      Leu codon families before UAA; and UCA(Ser), AUG(Met), and the Phe codon family
      before UAG. In contrast, the Thr and Gly codon families were under-represented
      before UGA, while ACC(Thr) and the Gly codon family were under-represented before
      UAG and UAA respectively. In an earlier study, uridine was shown to be over
      represented in position -3 before UGA in Escherichia coli [Arkov,A.L.,
      Korolev,S.V. and Kisselev,L.L. (1993) Nucleic Acids Res., 21,2891-2897]. In that
      study, the codons for Lys, Phe and Ser were shown to be over-represented
      immediately upstream of E. coli stop codons. Consequently, E. coli and human
      termination codons have similar 5' contexts. The present study suggests that the
      5' context of stop codons may modulate the efficiency of peptide chain
      termination and (or) stop codon readthrough in higher eukaryotes, and that the
      mechanisms of such a modulation in prokaryotes and higher eukaryotes may be very
      similar.

PMID- 8524666
TI  - Occurrence, solution structure and stability of DNA hairpins stabilized by a
      GA/CG helix unit.
AB  - The occurrence and NMR solution structure of a class of biloop hairpins
      containing the sequence 5'-CGXYAG are presented. These hairpins, which are
      variations on a sequence found in the reverse transcript of the human T-cell
      leukemia virus 2 (HLV2), show elevated melting points and high chemical stability
      toward denaturation by urea. Hairpins with the 5'-CGXYAG configuration have
      melting points 18-20 degrees higher than hairpins with 5'-CAXYGG or 5'-GGXYAC
      configurations. The identities of the looping bases, X and Y above, play a
      negligible role in determining the stability of this DNA hairpin stability. This
      is very different from G-A based loops in RNA, where the third base must be a
      purine for high stability [the GNRA loops; V.P. Antao, S.Y. Lai and I. Tinoco, Jr
      (1991) Nucleic Acids Res., 19, 5901-5905]. We show that these properties are
      associated with a four base helix unit that contains both a sheared GA base pair
      and a Watson-Crick CG base pair upon which it is stacked. As an understanding of
      the significance of AG base pairs has become increasingly important in the
      structural biology of nucleic acids, we compute an 0.7-0.9 A precision ensemble
      of NMR solution structures using iterative relaxation matrix methods.
      Calculations performed on NMR-derived structures indicate that neither base-base
      electrostatic interactions, nor base-solvent dispersive interactions, are
      significant factors in determining the observed differences in hairpin stability.
      Thus the stability of the 5'-CGXYAG configuration would appear to derive from
      favorable base-base London/van der Waals interactions.

PMID- 8524667
TI  - Inhibition of cell proliferation by C/EBP alpha occurs in many cell types, does
      not require the presence of p53 or Rb, and is not affected by large T-antigen.
AB  - The transcription factor CCAAT/enhancer binding protein (C/EBP alpha) is
      expressed predominantly in differentiated tissues and is able to induce growth
      arrest and differentiation in preadipocytes. C/EBP alpha expression is high in
      non-dividing hepatocytes, but decreases during liver regeneration. These
      observations suggest that C/EBP alpha is inversely related to cell proliferation.
      To investigate the mechanism of growth inhibition by C/EBP alpha, the response of
      immortal human cells to cotransfection of a C/EBP alpha expression vector (CMV
      alpha) and a CMV beta-galactosidase expression vector was examined. Hep3B2, a
      hepatoma; Saos2, an osteosarcoma deficient for p53 and Rb; and 639, a fibroblast
      expressing SV40 T-antigen, were examined. Transiently transfected cells were
      stained for beta-gal activity to monitor their ability to undergo division. The
      ability of stable transformants to form colonies was also assessed for each cell
      line. Cells transfected with CMV alpha remained as non-dividing cells while
      control cells divided to form colonies. Mutations of the C/EBP alpha sequence
      demonstrated that only a small, previously uncharacterized activation domain was
      required for antimitotic activity. Our results suggest that C/EBP alpha may play
      a role in maintaining the quiescent state of hepatocytes and other cells.
      Furthermore, it appears that the effects of C/EBP alpha are not mediated through
      p53 or Rb and are not altered by T-antigen.

PMID- 8524668
TI  - A rapid method for detecting and mapping in vitro transcripts from supercoiled
      templates using endogenous RNase H.

PMID- 8524669
TI  - Prevention of product carry-over by single tube two-round (ST-2R) PCR:
      application to BCR-ABL analysis in chronic myelogenous leukemia.

PMID- 8524670
TI  - Overcoming limitations of the mRNA differential display technique.

PMID- 8524671
TI  - Detecting differences in 5-methylcytosine using restriction enzyme isoschizomers:
      an endogenous control for complete digestion.

PMID- 8524672
TI  - Solid-phase reversible immobilization for the isolation of PCR products.

PMID- 8524673
TI  - Documentation and outcomes of advanced nursing practice.
AB  - PURPOSE/OBJECTIVES: To review literature related to documentation and evaluation
      of the competency of advanced practice nurses (APNs) and outline consensus
      findings specific to this area from the State-of-the-Knowledge Conference on
      Advanced Practice in Oncology Nursing. DATA SOURCES: Published articles in
      professional journals and written summations from the conference. DATA SYNTHESIS:
      Documentation and evaluation of APN competency is characterized by continued
      questioning about optimum approaches and methods. The literature to date has
      offered suggestions to initiate evaluation in APN practice. When documenting and
      evaluating APN competency, quality enhancement efforts and indices of cost
      effectiveness must be considered. To expand APN practice opportunities,
      documentation and evaluation must be considered as a desired and necessary
      quantification of practice and not just as extra work. Efforts to promote this
      way of thinking will enhance marketability of the APN role in cancer care.
      CONCLUSION: Little research of APN outcomes exists. To counter this paucity, ONS
      and other organizations need to develop theoretical models to support outcomes
      documentation, which, in turn, enhances political and organizational savvy and
      promotes a viable future for APNs. NURSING IMPLICATIONS: Improved documentation
      of nursing interventions is required to justify the necessity and effectiveness
      of the APN role. In the ever-changing arena of health and cancer care, oncology
      APNs must ensure their positions in both existing and evolving marketplaces
      though efficient documentation and evaluation.

PMID- 8524674
TI  - Education of the advanced practice nurse in oncology.
AB  - PURPOSE/OBJECTIVES: To review the education of the advanced practice nurse (APN)
      with a focus on curriculum and issues related to the oncology specialization.
      DATA SOURCES: The State-of-the-Knowledge Conference on Advanced Practice in
      Oncology Nursing, journal articles, monographs, and authors' personal
      experiences. DATA SYNTHESIS: APN education is a current issue in nursing, as well
      as in the specialty of oncology nursing. Current trends in the delivery of health
      care require reform of graduate education in nursing to better prepare APNs to
      shape and respond to the healthcare needs of the public along the entire cancer
      care continuum. CONCLUSIONS: APN education remains a dynamic, ever-evolving
      enterprise. The Oncology Nursing Society (ONS) and the American Cancer Society
      (ACS) have taken a proactive stand on APN education by revising master's
      curriculum guidelines and supporting the conference. IMPLICATIONS FOR NURSING
      PRACTICE: APN education in oncology will be an ongoing area of exploration for
      both ONS and ACS, as well as for leaders in oncology nursing. Development of
      graduate, postgraduate, and continuing education programs at the APN level of
      expertise will support high-quality advanced practice in oncology nursing. The
      feedback mechanisms among practice, education, and research will provide
      educational programs that will make a difference in the care of patients with
      cancer.

PMID- 8524675
TI  - Prescriptive authority for advanced practice nurses: current and future
      perspectives.
AB  - PURPOSE: To present an overview of the issues related to prescriptive authority
      and advanced practice nurses (APNs) in oncology. DATA SOURCES: Professional
      journals and books, print media, and professional and government releases. DATA
      SYNTHESIS: Discussion of issues related to complex political, educational,
      economic, and healthcare environmental factors. Strategies to achieve increased
      recognition for APN prescriptive authority include increasing APNs' knowledge
      about the effects of the political process on prescriptive authority, educating
      legislators and consumers, promoting standardization of pharmacology curricula,
      and encouraging formation of coalitions. CONCLUSIONS: Failure to pass a national
      healthcare plan, escalating managed-care markets, and the reform efforts of
      individual states to forge their own healthcare initiatives will challenge the
      APN's ability to practice and prescribe. IMPLICATIONS FOR NURSING PRACTICE: The
      subject of prescriptive authority highlights the controversies and debates that
      APNs encounter in a dynamic healthcare environment. These include the complexity
      of state-to-state regulations, non-nursing professions making key decisions
      regarding scope of practice and prescriptive authority, and the challenge for
      APNs to carve out new roles while overcoming state regulatory inconsistencies and
      market-reform barriers. If not resolved, these issues will continue to prevent
      qualified APNs from providing appropriate and comprehensive care to patients with
      cancer.

PMID- 8524676
TI  - Reimbursement issues for advanced practice.
AB  - PURPOSE/OBJECTIVES: To review issues regarding reimbursement for services
      provided by advanced practice nurses (APNs). DATA SOURCES: Published articles,
      book chapters, and professional experiences. DATA SYNTHESIS: Historically,
      barriers have prevented APNs from practicing to the full extent of their
      capabilities. One barrier is the lack of consistent reimbursement for services
      provided at the state and federal levels. A number of strategies can be
      implemented to simplify reimbursement. CONCLUSIONS: APNs must receive direct
      reimbursement for the services provided to work effectively in the current
      healthcare arena. IMPLICATIONS FOR NURSING PRACTICE: Direct reimbursement will
      enable APNs to control their practice, thus increasing healthcare accessibility
      and availability to individuals who currently have limited access to medical
      care.

PMID- 8524677
TI  - Regulation of advanced nursing practice: Part One--Second licensure.
AB  - PURPOSE: To present an overview of the issues relating to second licensure and
      advanced nursing practice in oncology and to summarize recommendations regarding
      second licensure from the State-of-the-Knowledge Conference on Advanced Practice
      in Oncology Nursing. DATA SOURCES: Published journal articles, a position paper
      and survey prepared by the National Council of State Boards of Nursing, and
      papers presented at the conference. DATA SYNTHESIS: The use of second licensure
      to regulate advanced nursing practice is controversial and has advantages and
      disadvantages. CONCLUSIONS: The Oncology Nursing Society should not adopt a
      position on second licensure until more is known about its advantages and
      disadvantages. IMPLICATIONS FOR NURSING PRACTICE: Advanced practice nurses must
      understand how licensure laws affect their scope of practice, their prescriptive
      authority, reimbursement, and other practice issues.

PMID- 8524678
TI  - Regulation of advanced nursing practice: Part Two--Certification.
AB  - PURPOSE/OBJECTIVE: To present an overview of issues related to the use of
      advanced practice nursing (APN) certification. DATA SOURCES: Published articles,
      position papers, and colleague experiences. DATA SYNTHESIS: Certification is used
      for credentialing APNs at the state level, and in some states, it is a
      requirement for second licensure. Presently, a great deal of variability exists
      in the purposes and procedures related to certification processes, thus devaluing
      its use. CONCLUSION: The lack of consistency among certifying agencies and the
      lack of documented impact of certified advanced nursing practice can negatively
      affect the value placed on certification as an advanced practice credential. In
      the current climate of increased regulation, nursing must maintain control of
      practice regulation. IMPLICATIONS FOR NURSING PRACTICE: Inconsistencies between
      states and among nursing organizations can negatively affect the mobility and
      career flexibility of APNs. The evaluation of outcomes related to certified
      advanced nursing practice must be a research priority in the current climate.
      Collaboration among specialty organizations also must occur to increase the
      credibility of certification as a nursing credential.

PMID- 8524680
TI  - In critical condition: management of dental trauma.

PMID- 8524679
TI  - Titling for advanced practice nurses.
AB  - PURPOSE/OBJECTIVES: To describe salient discussion points and the recommendations
      for titling of the advanced practice nurse (APN). DATA SOURCES: Discussion
      points, professional literature on titling for APNs, and rationale and
      recommendations generated by conference participants. DATA SYNTHESIS: The
      recommendation for a single title--advanced practice nurse--as an umbrella term
      to include clinical nurse specialists and nurse practitioners within the Oncology
      Nursing Society evolved from the desire to facilitate advancement of these roles.
      CONCLUSION: A common title for all nurses in advanced practice will help them to
      speak with one voice. IMPLICATIONS FOR NURSING PRACTICE: The existing healthcare
      environment provides numerous opportunities for APNs. Single titling may produce
      unity among APNs, provide the ability to speak with a single voice, and result in
      new opportunities for leadership roles in directing health care for the future.

PMID- 8524681
TI  - A comparison of conventional versus electronic monitoring of sedated pediatric
      dental patients.
AB  - The first purpose of this study was to compare traditional monitoring methods to
      electronic instruments for monitoring physiologic parameters during conscious
      sedation of pediatric dental patients. Traditional methods included careful
      visual assessment of skin color, airway patency and chest movements, and
      auscultation of breath and heart sounds using a precordial stethoscope;
      electronic instruments included the capnograph and pulse oximeter. The second
      purpose of the study was to examine the potential of the capnograph to provide
      more advanced warning than the pulse oximeter for respiratory compromise. Thirty
      nine children (mean age 39 months) received an oral sedative regimen of chloral
      hydrate, hydroxyzine pamoate, and meperidine and all were supplemented with 100%
      oxygen via nasal cannula throughout their sedations. One investigator used
      traditional monitoring and the other used electronic--both monitored
      simultaneously while being shielded (blinded) from each other. Electronic
      monitoring yielded a false alert rate of 88% compared with 73% for traditional
      monitoring. Ten confirmed episodes of respiratory compromise were identified
      electronically and only three were identified by traditional monitoring. All of
      the 10 confirmed respiratory compromise episodes were detected by capnography;
      none were detected by oximetry. During these 39 pediatric sedations using a
      narcotic drug regimen and 100% oxygen supplementation, there were no true
      desaturations.

PMID- 8524682
TI  - Treatment of fluorosed and white-spot human enamel with calcium sucrose phosphate
      in vitro.
AB  - A number of treatments have been devised to improve the appearance of fluorosed
      enamel. However, many of these have been empirically based, and the success of
      the various treatment regimens have not been quantitated. In this study, the
      relative whiteness of normal, mildly fluorosed, moderately fluorosed, and carious
      white-spot lesions on extracted teeth was quantitated by light reflectance using
      a Minolta Chroma Meter. The color was again determined following a number of
      treatment regimens to assess the potential use of various agents in treating the
      enamel lesions. Treatment of the enamel with a 35% hydrogen peroxide gel resulted
      in a significantly increased whitening, which was not reduced by subsequent
      treatment (P < 0.05). Removal of the enamel surface with a dental bur, followed
      by treatment with 5.25% sodium hypochlorite and placement in an artificial saliva
      was successful for returning white-spot lesions to a normal enamel color.
      Treatment of enamel with 5.25% sodium hypochlorite followed by calcium sucrose
      phosphate paste and placement in artificial saliva was most successful in
      returning both white-spot and fluorosed lesions to a normal color. SEM imaging of
      the calcium sucrose phosphate treated enamel suggests that this treatment filled
      the porous enamel, resulting in a normal light reflectance from the enamel.

PMID- 8524683
TI  - Effect of familial hypophosphatemic rickets on dental development: a controlled,
      longitudinal study.
AB  - Familial or X-linked hypophosphatemic rickets (XLHR) is the most common type of
      rickets in developed countries today. While the dental manifestations of rickets
      are well reported, there is little information regarding its relationship to
      dental development and other dental anomalies. This investigation studied the
      rate of dental development and associated dental anomalies in 19 XLHR subjects
      compared with 38 race-, age-, and sex-matched control children. The results
      showed that in both XLHR and control children, no significant differences existed
      in dental age compared with the respective chronological age, indicating that
      rickets did not affect the rate of dental development. Longitudinal growth curves
      of seven XLHR and matched control children substantiated that relationships of
      dental to chronological ages were comparable in both groups. Male XLHR subjects
      showed significantly increased tendency for dental taurodontism with mean Crown
      Body (CB):Root (R) ratio of 1.1 compared with 1.0 in females and 0.8 in controls
      (P < 0.02). Male XLHR children also showed significantly increased prevalence
      (50%) of ectopic permanent canines compared with control children (8%, P < 0.01).

PMID- 8524684
TI  - In vitro inhibition of bacteria from root canals of primary teeth by various
      dental materials.
AB  - The primary tooth pulpectomy is a common clinical procedure. The choice of
      filling material is important to the success rate, but antibacterial properties
      of such materials against organisms known to inhabit infected primary root canals
      have not been well documented. This study compared the antibacterial
      effectiveness of 10 materials: 1. Calcium hydroxide mixed with camphorated
      parachlorophenol (Ca(OH)2+CPC) 2. Calcium hydroxide mixed with sterile water
      (Ca(OH)2+H2O) 3. Zinc oxide mixed with CPC (ZnO+CPC) 4. Zinc oxide mixed with
      eugenol (ZOE) 5. ZOE mixed with formocresol (ZOE+FC) 6. Zinc oxide mixed with
      sterile water (ZnO+H2O) 7. ZOE mixed with chlorhexidine dihydrochloride (ZOE+CHX)
      8. Kri paste 9. Vitapex paste 10. Vaseline (control) These materials were
      compared against microbial specimens obtained from 13 infected primary teeth by
      using an agar diffusion assay. The results suggest that the materials could be
      divided into three categories. Category I, with the strongest antibacterial
      effect included ZnO+CPC, Ca(OH)2+CPC, and ZOE+FC. Category II, with a medium
      antibacterial effect included ZOE+CHX, Kri, ZOE, and ZnO+H2O. Category III, with
      no or minimal antibacterial effect included Vitapex, Ca(OH)2+H2O, and Vaseline.
      There were no significant differences within each category, but there were
      significant differences between the categories. The one exception was the
      antibacterial effect of ZOE+FC which was not significantly different from
      ZOE+CHX, Kri, or ZOE.

PMID- 8524685
TI  - The effect of topical APF foam and other fluorides on veneer porcelain surfaces.
AB  - Some topical fluorides cause surface changes in dental materials. The purpose of
      this study was to compare the effects of a topical acidulated phosphate sodium
      fluoride (1.23% APF) foam with the effects of other topical fluorides on the
      surface of veneer porcelain. Forty porcelain specimens (Ceramco) were placed into
      eight groups (N = 5). Four groups were immersed in either 1.23% APF foam, 1.23%
      APF gel, 2.0% sodium fluoride (NaF) gel, or water (reference) for 1 min. The
      other four groups were immersed in one of the above agents for four 1-min
      immersions. The surface topography of two scanning electron micrographs of each
      specimen was scored visually by two raters and by computer digital analysis
      (CDA). Inter-rater reliability was r = 0.67 (intraclass correlation coefficient).
      There were no significant differences in the mean visual scores or CDA scores
      among any of the groups immersed for 1 min. Porcelain immersed 4 min in APF gel
      had significantly greater mean visual scores and CDA scores than the other
      treatments (P < or = 0.0001; one-way ANOVA and Tukey's Studentized Range Test).
      The average surface topography scores of veneer porcelain immersed for 1 min in
      1.23% APF gel, 2.0% NaF gel, 1.23% APF foam, or water were not significantly
      different. Significantly greater surface topography scores occurred following 4
      min of immersion in 1.23% APF gel than all other agents.

PMID- 8524686
TI  - Talon cusp affecting the primary maxillary central incisors in two sets of female
      twins: report of two cases.

PMID- 8524687
TI  - Juvenile ossifying fibroma of the maxilla in a 6-year-old male: case report.

PMID- 8524688
TI  - Guided tissue regeneration in managing an incisor with a labially fused
      supernumerary: case report.

PMID- 8524689
TI  - Eruption of an impacted second premolar after marsupialization of a large
      dentigerous cyst: case report.

PMID- 8524690
TI  - Dominant research interests of pediatric dentists: dental materials, craniofacial
      biology and cariology.

PMID- 8524691
TI  - The case review section.

PMID- 8524692
TI  - Management of trauma in the child and adolescent.

PMID- 8524693
TI  - [How to prevent diabetic nephropathy or to delay its development].

PMID- 8524694
TI  - [The effect of treatment with propafenone, metoprolol and amiodarone on
      lymphocyte sodium efflux and level of cAMP in serum].
AB  - The effect of long-term treatment with propafenone, metoprolol and amiodarone was
      studied on the activity of Na,K-adenosine triphosphatase in lymphocytes and the
      plasma level of cAMP in patients with ventricular arrhythmias. The investigations
      were carried out in 86 patients with cardiac dysrhythmias caused by coronary
      artery disease, hypertension, post-inflammatory and alcohol cardiomyopathy and
      preexcitation syndrome. Propafenone was used in treatment in 31 patients,
      metoprolol in 30, amiodarone in 25. The activity of of Na,K-adenosine
      triphosphatase in lymphocytes was estimated by the method of Heagerty et al. The
      plasma level of cAMP was measured radioimmunologically. Disappearance of
      ventricular arrhythmias after treatment was accompanied by increase in activity
      of of Na,K-adenosine triphosphatase and decrease in plasma level of cAMP
      regardless of which drug was used. Ineffective treatment did not affect both
      parameters.

PMID- 8524695
TI  - [The effect of human recombinant erythropoietin on levels of plasma phospholipids
      in patients chronically treated with hemodialysis].
AB  - In uremic patients a disturbed lipid metabolism is observed. In our former works
      a positive effect of erythropoietin (EPO) on blood platelet phospholipids
      composition in uremic patients was indicated. In this study we examined the EPO
      influence on blood plasma phospholipids in chronically hemodialyzed patients.
      Phospholipids were measured by thin layer chromatography method before and 3
      months after the beginning of EPO treatment. EPO was administered subcutaneously,
      2000 U twice a week. Decreased phosphatidylethanolamine, phosphatidylinositol and
      phosphatidylcholine levels were shown in patients before EPO treatment, compares
      with the control group. During EPO therapy the phospholipid levels approached to
      normal values. Conclusion is that EPO administration has a positive influence on
      blood plasma phospholipids in hemodialyzed patients. The detailed importance of
      this event has been not known yet, but our observations suggest that EPO
      profoundly interferes with lipid metabolism.

PMID- 8524696
TI  - [Blood platelet function, plasma serotonin and lipid metabolism in patients with
      diabetic nephropathy].
AB  - Accelerated atherosclerosis is commonly observed in diabetes mellitus as well as
      in some kidney diseases. This may be partly due to platelet hyperactivity.
      Serotonin (5-HT) is thought to play a role in platelet/vessel wall interactions
      and to be implicated in the pathogenesis of atherosclerosis. The aim of the study
      was to evaluate platelet aggregation and peripheral serotonergic system in
      patients with diabetic nephropathy. The studies were performed in 37 patients
      with diabetic nephropathy (age 53.5 +/- 14.9) and healthy volunteers (age 44.2 +/
      12.3). Platelet aggregation (in PRP according to Born) induced by collagen (2
      micrograms/ml), ADP (5 microM), epinephrine (10 microM) arachidonic acid (0.25
      mM) and 5-HT (1 microM) was found to be significantly enhanced in diabetic
      relative to controls. Whole blood 5-HT was significantly lower in diabetics
      patients, whereas plasma 5-HT was significantly higher in diabetic patients when
      compared to controls. Since serotonin can amplify platelet aggregatory responses
      to various agonists, platelet hyperactivity in diabetes may be in part due to an
      enhanced availability of this amine. Disturbances in peripheral serotonergic
      system together with platelet hyperaggregability may be associated with an
      increased incidence of cardiovascular complications in diabetes.

PMID- 8524697
TI  - [Analysis of heart rhythm variability in evaluation of treatment for unstable
      angina pectoris].
AB  - Unstable angina pectoris is accompanied by several unfavourable autonomic
      disturbances. A noninvasive assessment of the autonomic cardiac control is
      possible by means of heart rate variability analysis (HRV). 26 patients with
      unstable angina pectoris were enrolled in the study. All patients received
      obligatory nitroglycerin and heparin intravenously within two days, and
      gallopamil (G) or metoprolol (M) together with aspirin or ticlopidine orally
      randomly, which were continued for 3 month or shorter if coronary
      revascularization was earlier performed. 512 R-R intervals was registered in each
      patient at 7th day of hospitalization and in 14th at the time of admission.
      Kardioassist v.1.0 system was used for heart rate variability analysis. After
      analog to digital conversion, with 12 bit resolution and 1000 Hz of sampling
      rate, seriogram of R-R intervals was obtained, and then power spectrum density
      was computed with the Fast Fourier Transform. Time-domain analysis provided mean
      (basic) R-R interval (BCL) and its standard deviation (SD-RR). In frequency
      domain the following spectral variables were analysed: power spectral density
      (s2/Hz) of the high frequency component (aHF, 0.15-035 Hz), low frequency
      component (aLF, 0.05-0.15 Hz) and very low frequency component (aVLF, 0.004-0.05
      Hz), percentage power of respective components (%HF, %LF and %VLF) and autonomic
      balance indices: aLF:aHF and %LF:%HF. These variables were compared in patients
      treated with G (13 patients) against those with M (13 patients). Additionally,
      the effects of treatment regimen was evaluated also in 14 patients, in whom HRV
      analysis was performed at admission and 7 days later.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8524698
TI  - [Clinical and immunologic characteristics of CD 34 positive acute myeloid
      leukemia].
AB  - Expression of antigen CD 34+ on acute myeloid leukemia is admittedly regarded as
      a negative prognostic factor, however some authors deny it. The aim of our
      studies was clinical, morphological and immunological analysis of AML CD 34+. In
      the group of 39 patients with de novo AML there was 46% of AML CD 34+ (18 cases-
      14 women and 4 men aged 18 to 80 years--mean 52.5). The diagnosis was made
      according to FAB criteria and immunophenotype estimation by immunocytochemical
      method APAAP. The following types of AML were found: MO-4 cases, M1-1, M2-4, M4
      8, M5-1. Analysis of clinical features of AML CD 34+ did not show any
      characteristic features either in peripheral blood smear, or bone marrow smear.
      Most patients were treated according to the EPR+Ara-C scheme, with addition of VP
      16 in M4 types, one patient--IDA+VP-16 + Ara-C, three elderly patients were
      treated with low doses of Ara-c, one patient refused cytostatic treatment. Three
      patients achieved complete remission (17.6%), three achieved partial remission
      (17.6%), four died during the phase of aplasia and seven others (41.2%) were
      completely resistant for chemotherapy. These results confirm association between
      CD34 expression and drug resistance.

PMID- 8524699
TI  - [The effect of hypotensive drugs on left ventricular mass and diastolic
      function].
AB  - Chronic left ventricular hypertrophy (LVH) is associated with depressed
      contractile performance, abnormal compliance of the chamber, and ultimately, the
      development of a left ventricular failure. Thus the presence of LVH carries a
      particularly ominous prognosis in patients with essential hypertension. Finally,
      regression of LVH appears to be a worthwhile goal of an antihypertensive therapy
      along with blood pressure control. Of particular importance, is whether the
      functional derangements associated with hypertrophy will also be reversed. The
      present study was undertaken to determine whether antihypertensive therapy
      reduced ventricular mass, and whether these changes were accompanied by improved
      diastolic function. 47 patients with mild-to-moderate essential hypertension were
      divided into two groups. Group I--included 21 patients whose blood pressure
      responded to nifedipine monotherapy. Group II--included 26 patients whose
      normalization of blood pressure required combined therapy with nifedipine and
      metoprolol. 40 healthy volunteers comprised a control group. To assess the
      effects of antihypertensive therapy on the heart, left ventricular mas (LVM),
      systolic and diastolic function, by M-mode, 2-D and pulsed wave Doppler
      echocardiography had been evaluated. Measurements were performed before therapy
      and every 3rd month during first year, and every 40th month during the second
      year of observation. RESULTS. At baseline all hypertensive patients had
      significantly increased LVM compared to the controls. Indexes of systolic
      function in studied patients were normal, while indexes of LV diastolic filling
      were significantly abnormal compared to the controls. In the group treated with
      nifedipine, starting from the 9th month of observation, small but significant
      decrease in posterior wall thickness was noted but LVM did not change during the
      whole time of the observation. Similarly, there was no significant change in
      indexes of left ventricular diastolic filling. Contrary to patients treated with
      nifedipine, in group of patients treated with combination of nifedipine and
      metoprolol, significant reduction of LVM and improvement of LV diastolic filling
      was observed. Of particular interest was the fact, that improvement in diastolic,
      performance appeared earlier, and preceded regression of LVM. Most striking was
      the improvement in Ev/Av ratio which increased by 16% after 6 months and by 35%
      after 24 months of the therapy. CONCLUSION. 1. Combined therapy with nifedipine
      and metoprolol contrary to monotherapy with nifedipine alone, results in the
      regression of left ventricular mass and the improvement of left ventricular
      diastolic function. 2. Improvement of left ventricular diastolic function appears
      earlier, preceding the regression of left ventricular hypertrophy.

PMID- 8524700
TI  - [The role of long-acting beta-mimetics in patients with chronic bronchial spasm
      and bronchial asthma].

PMID- 8524701
TI  - [Difficulties in diagnosis of cytomegalovirus mononucleosis syndrome].
AB  - A case of a healthy 23-year-old woman is reported with cytomegalovirus
      mononucleosis as a result of infection of cytomegalovirus probably primary. The
      patient presented with symptoms of generalized adenopathy, migratory arthralgias
      and arthritis, hepatosplenomegaly, long lasting rash as well as complications of
      pneumonia and myocarditis. Because on histopathological examination of lymph node
      the Hodgkin-Reed-Sternberg-like cells were found a misdiagnosis of Hodgkin's
      disease was initially made. After about 8 weeks period there was a complete
      recovery. The current problems related to cytomegalovirus infection are
      presented.

PMID- 8524702
TI  - [Tumor-infiltrating lymphocytes (TIL)].

PMID- 8524703
TI  - [Effect continuous positive airway pressure (CPAP) on left ventricular diastolic
      function in patients with obstructive sleep apnea syndrome--OSAS].
AB  - 22 patients with (OSAS) obstructive sleep apnea syndrome were divided into two
      groups: patients with OSAS and without arterial hypertension, and OSAS with
      hypertension. The effect of CPAP (continuous positive airway pressure) on the
      left ventricular function was evaluated using 2D and Doppler echocardiography.
      Systolic left ventricular function (ejection fraction) was normal in all
      patients. The decrease in peak mitral flow velocity during early diastole E
      (m/sec), the increase of atrio-systolic contraction A (m/sec), the increase in
      E/A and prolonged isovolumic relaxation time (IVRT) was observed in the both
      groups at the beginning of the study. After three month treatment with CPAP the
      increase in the ratio E/A, 1.38 + 0.23 m/sec vs 0.98 + 0.28 (p < 0.05) and a
      reduction in IVRT, 79 + 6.8 milisec vs 91.3 + 6.3 (p < 0.05) in the group with
      OSAS and hypertension was observed. In the group with OSAS and without
      hypertension only a statistically significant reduction in IVRT was observed,
      77.8 + 5.4 vs 83.7 + 5.15 milisec p < 0.05.

PMID- 8524704
TI  - Right ventricular size and function as assessed by echocardiography and
      angiography in patients with different volume load.
AB  - A comparative study of right ventricular (RV) function, assessed by
      echocardiography and angiography, undertaken in 20 patients, 10 of whom had
      atrial septal defects (ASDs) and 10 had various other heart diseases. All of the
      measured echocardiographic variables of RV size, apart from RV length, were
      larger in the patients with ASD. When assessed by multiple regression analysis,
      the RV M-mode dimension was an independent variable of RV angiographic end
      diastolic volume (EDV) in patients without RV volume load (R = 0.92, R2 = 0.85, p
      < 0.001). In the patients with ASD, echocardiographic RV end-diastolic area was
      an independent variable of angiographic RVEDV (R = 0.75, R2 = 0.55, p < 0.05),
      whereas M-mode dimension had a weaker correlation (r = 0.29). The agreement
      between RV ejection fraction (RVEF) obtained by echocardiography and angiography
      was moderate in both patient groups. However, fractional area change and
      fractional length change could not estimate RVEF better. Thus care should be
      taken to use single measurements and derivatives as the only parameters of RV
      size and function.

PMID- 8524705
TI  - Symptomatic heart disease in infants: comparison of three studies performed
      during 1969-1987.
AB  - We compare the data of three studies of hospitalized infants with cardiac disease
      performed between 1967 and 1987. The studies were from the New England Regional
      Infant Cardiac Program (1967-1974), the Brompton Hospital (1973-1982), and the
      Northern Great Plains Regional Cardiac Program (1982-1987). Considering
      differences in classification among the studies, the distribution of cardiac
      anomalies during the first year of life is similar among the three studies.
      Although about 30% of infants are admitted during the first week of life and
      nearly 40% between 3 and 6 months, the proportion of infants admitted between 6
      and 12 months was larger (25%) in the latest than in the earliest study (10%).
      There were also differences in the distribution of the diagnoses at various ages,
      reflecting changes in the patterns of care during the three eras.

PMID- 8524706
TI  - Cardiovascular effects of high-dose growth hormone treatment in growth hormone
      deficient children.
AB  - Growth hormone (GH) hypersecretion is associated with an increased incidence of
      cardiac hypertrophy and subclinical abnormalities of left ventricular (LV)
      function. The unlimited availability of biosynthetic GH has led to progressively
      increased dosage when treating GH-deficient children, raising the question of its
      cardiovascular effects during long-term therapy. We compared 22 children (8
      girls, 14 boys), mean age 12.1 years (range 3-17 years) with GH deficiency who
      were receiving chronic GH treatment (GH group) with 22 normal controls matched
      for sex and body size in order to evaluate: (1) LV volume, mass, and systolic
      function by two-dimensional guided M-mode echocardiography; (2) LV diastolic
      function by pulsed-wave Doppler sampling of the transmitral flow; and (3) cardiac
      output and systemic vascular resistance by Doppler echocardiography. All patients
      had been on chronic GH therapy for 13.8 +/- 7.6 months (range 5-30 months) with
      an average dose of 0.95 +/- 0.12 IU/kg per week (range 0.69-1.17 IU/kg per week).
      Blood pressure did not differ between the two groups. LV volume, mass, ejection
      fraction, and mean velocity of circumferential shortening did not differ
      significantly between the GH group and controls; nor did the peak- and end
      systolic meridional stress. All patients had a normal contractile state as
      estimated by the relation between mean velocity of circumferential shortening and
      end-systolic meridional stress. The LV filling parameters did not differ between
      the two groups, and there was no difference in cardiac index and systemic
      vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524707
TI  - Verapamil-induced "primary" polydipsia.
AB  - An 11-month-old male infant with recurrent supraventricular tachycardia (SVT) was
      treated with oral verapamil. Shortly thereafter he developed marked changes in
      behavior including lethargy, intensely increased thirst and urination, and
      irritability when denied fluids. "Primary" polydipsia was diagnosed following an
      evaluation which showed no evidence of adrenal insufficiency, diabetes insipidus,
      diabetes mellitus, hypercalcemia, hyperosmolality, or renal disease. The symptoms
      resolved 1 week after verapamil was discontinued.

PMID- 8524708
TI  - Familial symptomatic sinus bradycardia: autosomal dominant inheritance.
AB  - Symptomatic sinus bradycardia, due to either sick sinus syndrome or vagotonia,
      can be familial, affecting several members of a family. We report an 18-year-old
      male patient with palpitations and limited exercise capacity who was noted to
      have severe sinus bradycardia. His resting heart rate was 40/min, with normal PR
      and corrected QT intervals, and sinus pauses up to 6 seconds during sleep.
      Exercise treadmill test and pharmacologic autonomic blockade during
      electrophysiologic studies abolished the bradycardia, suggestive of vagotonia
      rather than intrinsic sinus node dysfunction. This patient's father and a female
      cousin had a similar clinical history but associated with syncope and severe
      sinus bradycardia. The mode of transmission appeared to be autosomal dominant.
      All three have permanent demand pacemakers implanted and are asymptomatic.

PMID- 8524709
TI  - Newborn with congenital arteriovenous fistulas of the abdominal wall complicated
      by a ductus arteriosus aneurysm.
AB  - A case of congestive heart failure in a neonate resulting from a congenital
      abdominal arteriovenous fistula is described; an aneurysm of the ductus
      arteriosus was also found in the patient. Abdominal aortography was performed and
      demonstrated dilated feeding arteries, including the hypogastric arteries, which
      communicated with a dilated umbilical vein. Ligation of the feeding arteries and
      the umbilical vein led to resolution of the heart failure. Transient liver
      dysfunction occurred, however. Symptoms improved dramatically upon removal of the
      ligature from the umbilical vein. Although there is one previous report of an
      arteriovenous fistula involving the umbilical vein, we know of no prior report of
      a congenital arteriovenous fistula in association with a ductus arteriosus
      aneurysm.

PMID- 8524710
TI  - Hypoplastic left heart syndrome with male pseudohermaphroditism and bicornuate
      uterus bicollis.
AB  - A 39-week-old phenotypically female infant was born with hypoplastic left heart
      syndrome and expired on the third day of life. An autopsy revealed the patient to
      also have male pseudohermaphroditism and uterus bicornis bicollis. The
      association of hypoplastic left heart syndrome and male pseudohermaphroditism has
      been reported in only two previous patients.

PMID- 8524711
TI  - Atrioventricular septal defect and type A postaxial polydactyly without other
      major associated anomalies: a specific association.
AB  - Four children are described, (three black and one white, two boys and two girls)
      with type A postaxial polydactyly. All four of them, in addition, had either a
      partial or complete atrioventricular septal defect (AVSD). None of these children
      had associated major malformations. Minor anomalies were observed (e.g., two
      patients with hypersegmentation of the sternal segments, one patient with
      undescended testes, one patient with hypoplastic lumbar vertebra, and one patient
      with a degree of craniofacial abnormality). Chromosome analysis was carried out
      for three of the four patients, and was normal in all of them. It is suggested
      that there is a specific association between type A postaxial polydactyly and the
      AVSD found in each of these patients. This picture does not conform to, but bears
      some resemblance to, the Ellis-van Creveld syndrome.

PMID- 8524712
TI  - Chondrodysplasia punctata: case report and literature review of patients with
      heart lesions.
AB  - Chondrodysplasia punctata (CP) is sometimes accompanied by heart lesions, but the
      literature is not specific or consistent regarding the incidence or types of
      cardiac anomalies. A patient with the mild Conradi-Hunermann type of CP is
      peripheral pulmonary arterial stenoses. A review of the literature brought to
      light a total of 23 patients with congenital heart lesions that were mainly found
      among cases of Conradi-Hunermann type and autosomal recessively inherited CP.

PMID- 8524713
TI  - American Academy of Pediatrics section on cardiology meeting. San Francisco,
      California, 13-15 October 1995. Abstracts.

PMID- 8524714
TI  - Toward a unified-field theory of the pathogenesis of acquired immune deficiency
      syndrome.

PMID- 8524715
TI  - Matching.
AB  - Matching is an intuitively appealing design strategy for ensuring balance on one
      or more potential confounding variables, usually either among subjects who were
      exposed or unexposed to a suspected risk factor for disease in a cohort study or
      between diseased and nondiseased subjects in a case-control study. But does
      matching always automatically "control" confounding and is it always as good a
      strategy as it seems? It is the intention of this review to shed light on these
      questions primarily through illustrative examples of the effects of matching on
      the validity of point estimates of the odds ratio between exposure and disease
      status in both types of study designs. It is seen that the results of matching
      are more or less in line with expectations in cohort studies, but that matching
      can lead to unexpected results in case-control studies. In a case-control study,
      confounding is not automatically controlled by matching per se; rather, matching
      and a statistical analysis that properly accounts for the matching are needed to
      obtain a valid estimate of effect in a case-control study design.

PMID- 8524716
TI  - The tribal tobacco policy project: working with Northwest Indian tribes on
      smoking policies.
AB  - BACKGROUND: This article reports on the objectives, study design, intervention
      methods, baseline results, and process data from a trial involving 39 Northwest
      Indian tribes. METHODS: Tribes were stratified and then randomized to either
      early or late intervention conditions. Intervention consisted of a consultation
      process to assist tribes to review and modify existing tobacco policies or to
      develop new policies relevant for their tribe and that protect tribal members
      from environmental tobacco smoke. Outcome measures consist of: (a) phone
      interviews to assess the comprehensiveness of tribal tobacco policy, (b) surveys
      of tribal leaders to assess norms and attitudes regarding tobacco use, and (c)
      observations of tribal settings to assess policy implementation and indicants of
      tobacco use. RESULTS: Early and later intervention tribes were well matched on
      baseline measures and tribal characteristics potentially related to policy
      outcomes. There was considerable variability across tribes on all measures
      though, in general, tribal leaders expressed support for more stringent tobacco
      use policies. Process data indicated that early intervention tribes strengthened
      their tobacco policies, but generally did not do so through tobacco policy
      committees as originally envisioned. CONCLUSIONS: There is good potential for
      tobacco policy interventions with Indian tribes. Consultation processes and
      products, such as policy guidebooks, that are sensitive to traditional uses of
      tobacco and to differences among tribes can help to modify policies to reduce
      exposure of tribal members to environmental tobacco smoke.

PMID- 8524717
TI  - Prevalence of smoking among adult American Indian clinic users in northern
      California.
AB  - BACKGROUND: The American Indian Cancer Control Project is a 5-year program funded
      by the National Cancer Institute designed to promote smoking cessation among
      adult Indians living in Northern California. This article describes the result of
      our smoking prevalence survey. Our Indian-specific program combines the
      physician's anti-smoking message with the efforts of Indian Community Health
      Representatives, who have access to the Indian patients' families and
      communities. The study sites consist of 4 urban and 14 rural American Indian
      clinics in Northern California. This article reports on the results of the
      smoking prevalence study conducted in the first phase of the project. METHODS: A
      total of 1,369 adult Northern California Indian patients at 18 Indian health
      clinics completed a questionnaire designed to assess smoking rates and patterns
      as well as health problems. Participants were adult American Indians attending 1
      of 18 Indian health care clinics in Northern California during 1991. The
      participants included patients waiting for appointments with the clinic
      physician, dentist, and nurses. RESULTS: Forty percent (37.35, 42.64; 95%
      confidence interval) of the adult population in the sample smoke cigarettes; they
      hold lenient attitudes toward smoking and began smoking at an early age. These
      patients rate obesity as the No. 1 health problem, followed by high blood
      pressure, arthritis/rheumatism, and problems with alcohol. The survey also found
      that the highest smoking rate was among the Sioux (62%), a non-California tribe.
      This was followed by high rates among native California tribes: Maidu (46%), Pit
      River (39%), Pomo (38%), Hupa (37%), and Yurok (32%).

PMID- 8524718
TI  - A breast and cervical cancer project in a native Hawaiian community: Wai'anae
      cancer research project.
AB  - BACKGROUND: This article describes a breast and cervical cancer control project
      in a Native Hawaiian community and presents preliminary findings from its first
      year. The project is community driven, with Native Hawaiian community
      investigators and advisors involved in all phases of the research project. Its
      purpose is to test the effectiveness of a culturally appropriate intervention as
      a means of increasing breast and cervical cancer screening practices among Native
      Hawaiian women. METHODS: This article discusses the process of community
      participation in the development of a baseline survey as well as selected
      findings from that survey. A baseline telephone survey was conducted to obtain an
      initial assessment of community knowledge, attitudes, and behavior related to
      cancer. Community representatives were an integral part of the research team that
      planned and implemented the survey. RESULTS: A total of 1,260 women drawn equally
      from the study and the control communities participated in the survey. A majority
      of those surveyed in both communities indicated adherence to cancer screening
      recommendations. Seventy-three percent of the women reported having obtained a
      Pap test during the past 2 years. Fifty-nine percent of women over 40 years of
      age reported having had a mammogram during the past 2 years. Twenty-eight percent
      reported having used Hawaiian remedies within the past year. Thirty-six percent
      of the women reported encouraging others to obtain cancer screening services.
      DISCUSSION: Though a majority of the target population are following cancer
      screening guidelines, a significant minority are not. While the project
      intervention aims to change the screening behavior of women not currently getting
      cancer screening, it plans to do so by enlisting the women already in compliance
      to reach others in their social networks who are currently not getting cancer
      screening. The involvement of community representatives, working alongside
      researchers, in baseline survey planning helped assure the survey was acceptable
      to the participants and the community as a whole. This process is illustrative of
      a participatory research commitment which underlies success in the early phase of
      this Native Hawaiian research project.

PMID- 8524719
TI  - Tobacco use: baseline results from pathways to health, a school-based project for
      southwestern American Indian youth.
AB  - BACKGROUND: This paper describes a school-based cancer prevention project for
      fifth- and seventh-grade Navajo and Pueblo Indian children living in the
      Southwest. Baseline data are presented from 714 students who completed
      questionnaires on smoking and smokeless tobacco. METHODS: Questionnaires were
      administered in the fifth- and seventh-grade classrooms prior to students
      receiving the Pathways to Health cancer prevention curriculum. RESULTS: In our
      sample there were increases from fifth to seventh grade in self-reported current
      cigarette use and intention to use. Also, boys were more likely to use and intend
      to use cigarettes than girls. The use of smokeless tobacco also increased with
      increasing grade level, though this trend was less pronounced for girls. A
      significant gender difference was found in the use of smokeless tobacco with boys
      reporting higher use. However, reported use by girls was higher than is typically
      noted for non-Hispanic white girls. CONCLUSIONS: There is evidence of
      experimentation and regular use of tobacco products by both Navajo and Pueblo
      boys and girls. Even more students indicate intention to use tobacco products in
      the future. These data confirm the need for primary prevention programs designed
      for this population of American Indians.

PMID- 8524720
TI  - Recognition and liking of tobacco and alcohol advertisements among adolescents:
      relationships with susceptibility to substance use.
AB  - BACKGROUND: Exposure to tobacco and alcohol advertising has been associated with
      adolescent substance use. However, it is not clear whether favorable reactions to
      advertising are an antecedent to or a consequence of substance use. This study
      investigated relationships between adolescents' levels of susceptibility to
      substance use and their recognition and liking of tobacco and alcohol
      advertising. METHOD: Eighth-grade students viewed pictures of tobacco and alcohol
      advertisements with brand names and identifying information obscured, attempted
      to identify the brand name and type of product being advertised, and rated their
      liking of the advertisements. Subjects were divided into three substance use
      status groups: nonsusceptible nonusers (have never used and do not intend to do
      so), susceptible nonusers (have not used but have not made a firm commitment not
      to experiment in the future), and users (have tried the substance). RESULTS:
      Susceptible nonusers liked the tobacco advertisements at a level that was
      significantly greater than that of the nonsusceptible nonsmokers and comparable
      to that of the users. Liking of the alcohol advertisements generally increased
      with alcohol use status. CONCLUSIONS: These results suggest that tobacco
      advertisements ostensibly targeted to adult smokers may have the effect of
      recruiting new adolescent smokers.

PMID- 8524721
TI  - Breast cancer screening and associated factors for low-income African-American
      women.
AB  - BACKGROUND: Recent reports suggest that much of the difference in breast cancer
      survival between African-Americans and whites could be reduced through greater
      access to and use of screening by African-American women. Few community-based
      studies have addressed screening-related issues among low-income African-American
      women. METHODS: A simple random sample of households was drawn; a total of 585
      women of age 40 or older were interviewed in their homes (response rate = 75%).
      Women were grouped into four stages of adoption of screening: participated
      regularly, participated nonregularly, heard of but never participated in
      screening, or never heard of it. Bivariate analyses were used to describe
      relations between screening (mammography, clinical breast examination, and breast
      self-examination) and mediating variables. RESULTS: Ninety percent of the women
      were not getting regular mammography screening, 36% had heard of but had never
      had mammography, and 33% had never heard of mammography. Strong associations were
      noted with predisposing, enabling, and reinforcing factors inhibiting screening
      at each stage of adoption. CONCLUSIONS: For women who had heard of, but who were
      not getting, regular screening, recommendations were made for improving screening
      procedures in primary care practices. For women who had never heard of screening,
      coordinated community and primary care interventions were recommended for moving
      them toward regular screening.

PMID- 8524722
TI  - Community organization to promote breast cancer screening among women ages 50-75.
AB  - BACKGROUND: To reduce breast cancer mortality, ways to promote the use of
      mammography screening among women age 50 and above are needed. Community
      organization may be a useful approach. METHODS: The Washington State Community
      Breast Cancer Screening Project involved implementation of promotional activities
      initiated by physician and lay community boards in two communities. Two
      comparable communities served as controls for evaluation purposes. Random-digit
      dial telephone interviews were used to assess recent use of mammography at
      baseline and follow-up in independent samples of women ages 50 to 75 from the
      four communities. The extent of exposure to intervention activities and the
      relationship between exposure to intervention activities and mammography use were
      estimated from data collected at follow-up. RESULTS: Exposure to patient
      reminders from physicians, wallet reminder cards, and newspaper advertisements
      were consistently related to mammography use. Physician office staff
      encouragement and a display board were significantly related to mammography use
      only in Intervention Communities A and B, respectively. Neither exposure to
      promotional activities nor the change in prevalence of mammography use was
      significantly higher in the intervention communities than in the comparison
      communities at follow-up. CONCLUSIONS: Although several activities were useful in
      promoting mammography use, organization of the community did not enhance efforts
      undertaken spontaneously by comparable communities.

PMID- 8524723
TI  - Evaluating the efficacy of the National Cholesterol Education Program adult
      treatment guidelines: cholesterol lowering intervention program.
AB  - BACKGROUND: A cross-sectional analysis was conducted to test the feasibility of
      the National Cholesterol Education Program Adult Treatment Panel I Guidelines
      (ATPI) in physician office practices. METHODS: Twenty-two physician practices in
      communities from western Pennsylvania and West Virginia were recruited. Using a
      patient tracking system, 9,171 patients were assessed for cholesterol screening
      and treatment by their physicians according to the ATPI guidelines. RESULTS:
      Cholesterol screening was ordered for 1,698 patients or 19% of the population
      visiting the physician offices. The reasons for not screening included the
      patient was already under therapy (2,371), screened within the past 5 years
      (1,714), or acutely ill at the time of the visit (1,691). The frequency of
      patient refusal for screening was low (444). However, the majority of patient
      diagnoses were based on a single lipid measurement, and only 817 or 56% of
      patients evaluated had lipoprotein measures obtained prior to treatment. Follow
      up measurement was not performed according to the ATPI schedule, and the
      magnitude of cholesterol response was inversely related to time to first follow
      up measurement. CONCLUSIONS: Many patients in these physician practices had
      initial cholesterol screening. However, repeat measurements as recommended for
      initial evaluation were not performed routinely, nor were most patients followed
      within the recommended 3-month time period. This lack of follow-up is detrimental
      to effective, long-term patient management since the magnitude of the cholesterol
      response is related to time of the first follow-up measurement.

PMID- 8524724
TI  - The effect among older persons of a general preventive visit on three health
      behaviors: smoking, excessive alcohol drinking, and sedentary lifestyle. The
      Medicare Preventive Services Research Team.
AB  - BACKGROUND: The U.S. Congress mandated evaluations, initiated in 1989, to
      determine whether extending Medicare benefits to include preventive services
      would improve health status, reduce costs of care, and improve health risk
      behaviors of beneficiaries. METHODS: The Johns Hopkins Medicare Preventive
      Services Demonstration was a randomized trial in which Medicare beneficiaries
      were assigned either to an intervention group that was offered yearly preventive
      visits for 2 years and optional counseling visits to their primary care provider
      or to a control group that received usual care. This report describes the effect
      of the intervention over a period of 2 years on smoking, problem alcohol use, and
      sedentary lifestyle. RESULTS: Differences were observed between the intervention
      and control groups in the extent to which changes occurred in smoking and problem
      alcohol use, but none of the differences was statistically significant. The
      proportion of smokers who quit was higher in the intervention group than in the
      control group (24.2 vs 17.9%, P = 0.09). However, a higher proportion of problem
      drinkers in the control group improved (67.1 vs 57.0%, P = 0.183). There was
      virtually no difference between the intervention and the control groups in the
      proportion with improvement in sedentary lifestyle. CONCLUSIONS: This study
      demonstrates the difficulty of bringing about health behavior change in older
      patients in the course of a yearly preventive visit for 2 years with their
      primary care physician when the visit encompasses screening and immunizations, as
      well as health behavior counseling directed by the physician. Further study is
      required to determine whether a more intense program of counseling for health
      behavior change among older persons by their primary care providers would be
      effective.

PMID- 8524725
TI  - Participants' characteristics in a French colorectal cancer mass screening
      campaign.
AB  - BACKGROUND: Participation by the target population is clearly a key element in
      the success of mass screening programs for colorectal cancer. In France,
      involvement of general practitioners in test distribution is essential to reach a
      satisfactory participation rate, but other forms of recruitment also have to be
      organized. The aim of this study was to determine the influence of demographic
      characteristics such as sex, age, and place of residence on the participation
      rate in a French mass screening according to different recruitment methods.
      METHODS: The Hemoccult IIR test was proposed in three consecutive ways:
      spontaneously by general practitioners and occupational doctors during
      appointments (phase 1), by postal invitation (phase 2), and finally by direct
      mailing of the test (phase 3). The target population consisted of 11,947 people
      between 45 and 74 years of age, living in a district of the French county of
      Calvados, between March 1991 and April 1993. RESULTS: The overall participation
      rate was 51.3%. Forty-nine percent of all the tests were done during phase 1, 31%
      during phase 2, and 20% during phase 3. The overall participation rate varied
      essentially according to the place of residence, from 65.5% in urban areas and
      48.9% in intermediate areas to 27.7% in rural areas. The overall participation
      rate was also higher for females (57%) than for males (45%) and for those 60
      years and older (53.9%) than for those below this age (49.2%). The proportion of
      tests done during phase 1 was lowest among the youngest and the oldest age groups
      (37.5% in the 45- to 49-year class and 45.2% in the 70- to 74-year class) and
      among people living in the rural environment (respectively 55.3%, 45.5%, and
      35.9% in urban, intermediate, and rural areas). CONCLUSIONS: This study shows
      that place of residence strongly influences the global participation rate in mass
      screening for colorectal cancer in France, whereas sex and age have little
      influence. Recruitment methods complementary to distribution by general
      practitioners must be organized, especially for the youngest and oldest age
      groups (45-49 years and 70-74 years) and above all for people living in rural
      areas. The social, cultural, and psychological reasons for these differences
      remain to be investigated, with the aim of adapting mass screening strategies to
      the different population groups.

PMID- 8524726
TI  - Smokers' baseline characteristics in the COMMIT trial.
AB  - BACKGROUND: Baseline telephone survey data from 10 COMMIT sites were submitted to
      statistical analyses to compare the smoking characteristics of non-Hispanic white
      (white), non-Hispanic black (black), Mexican-origin (Mexican), and Puerto Rican
      origin (Puerto Rican) smokers. RESULTS: White men and women were more likely to
      be classified as "heavy smokers" than members of other racial/ethnic groups,
      although black and Puerto Rican smokers were more likely than whites to increase
      their smoking rates on weekends. Whites were less likely to report stopping
      smoking in the past. White and Mexican smokers were most likely to smoke light or
      ultralight brands and least likely to smoke menthol cigarettes. Blacks were most
      likely to report smoking their first cigarette of the day within 10 min of
      waking. CONCLUSION: The differences and similarities among different groups of
      smokers may have important implications for understanding patterns of tobacco
      related disease in smokers from different racial/ethnic and sex groups.

PMID- 8524727
TI  - Prevention of cardiovascular risk factor elevations in healthy premenopausal
      women.
AB  - BACKGROUND: A number of factors contribute to increased risk of coronary heart
      disease (CHD) among postmenopausal women, including atherogenic changes in serum
      cholesterol profiles, weight gain, and decreases in physical activity during the
      menopause. To date, no study has attempted to prevent elevations in primary CHD
      risk factors as women experience menopause. METHODS: A sample of 535 healthy
      premenopausal women, ages 44-50, were recruited for an ongoing 5-year randomized
      prevention trial testing whether increases in low-density lipoprotein cholesterol
      (LDL-C) and body weight can be prevented during the menopause with a dietary and
      behavioral intervention. The aim was to reduce total dietary and saturated fat
      and cholesterol, prevent weight gain, and increase physical activity levels.
      Changes in CHD risk factors after the first 6 months of treatment were analyzed
      comparing 253 intervention and 267 assessment-only control participants. RESULTS:
      The intervention group showed significant reductions in total cholesterol (-0.34
      mmol/liter), LDL-C (-0.28 mmol/liter), triglycerides (-0.04 mmol/liter), weight (
      4.8 kg), waist-hip ratio (-0.008), systolic blood pressure (-3.5 mm Hg),
      diastolic blood pressure (-2.2 mm Hg), serum glucose levels (-0.06 mmol/liter),
      and HDL-C (-0.06 mmol/liter) and significant increases in physical activity (+383
      kcal). No significant changes were observed in the control group. CONCLUSION: Six
      month results suggested that participants were receptive to the preventive
      approach to CHD risk reduction and were successful in making initial positive
      lifestyle changes. Follow-up data will evaluate long-term adherence to the
      intervention and the interaction between adherence and physiological changes
      during menopause.

PMID- 8524728
TI  - Temperament and metabolic syndrome precursors in children: a three-year follow
      up.
AB  - BACKGROUND: Cross-sectional and predictive associations between temperament and
      some essential parameters of the metabolic syndrome were examined in children.
      METHODS: A 3-year follow-up study of 1,589 randomly selected, healthy, 6-, 9-, 12
      , and 15-year-old children was used. Somatic parameters studied were serum
      insulin, serum glucose, serum HDL cholesterol, serum triglycerides, systolic
      blood pressure, and body-mass index. Temperament of the subjects was rated by
      their mothers using a questionnaire and a semantic differential. RESULTS:
      Temperamental factors were related cross-sectionally to, as well as predicted
      for, the metabolic syndrome precursors over the 3-year period. Mental vitality
      and positive emotionality were likely to be related and positive emotionality
      were likely to be related to a low somatic risk level, whereas hyperactivity,
      negative emotionality (e.g., aggression and anger), responsivity to others, and
      cooperativeness were related to a high level of somatic risk. These associations
      were more evident in boys than in girls. CONCLUSIONS: It was suggested that
      temperament might be of importance in the early development of the metabolic
      syndrome.

PMID- 8524729
TI  - Health promotion and osteoporosis prevention among postmenopausal women.
AB  - BACKGROUND: Although there is a plethora of literature about osteoporosis, little
      is known about the attitudinal variables that may predict osteoporosis-preventive
      behaviors (OPBs) among postmenopausal women. This study examined the relationship
      between variables from the Health Promotion Model (HPM) and OPBs of calcium
      intake, exercise participation, and taking of estrogen/hormone replacement
      therapy (ERT/HRT). METHODS: One hundred women completed measures of benefits and
      barriers to calcium intake, exercise participation, ERT/HRT usage; self-efficacy;
      control of health; importance of health; and health status. Participants also
      reported their actual calcium intake, exercise participation, and use of ERT/HRT:
      RESULTS: Participants consumed an average of 1,243 mg of calcium from milk,
      yogurt, calcium-rich foods, and supplements; 81% participated in weight-bearing
      and resistant training exercise but on an irregular basis; and 31% were users of
      ERT/HRT at the time of data collection. There were significant relationships
      between some of the HPM variables and calcium intake and exercise participation.
      There was a significant difference between past and current users of ERT
      regarding benefits and barriers to taking hormones. Hormone users reported higher
      calcium intake and greater exercise participation than nonusers. CONCLUSION:
      There is early evidence that variables of the HPM are associated with OPBs. After
      continued testing, intervention programs for osteoporosis prevention may use
      variables of the HPM as a theoretical base for behavior changes.

PMID- 8524730
TI  - Smoking cessation and absence from work.
AB  - BACKGROUND: This study examines the relationship between smoking cessation and
      absence from work by analyzing data collected from a large sample of ex-smokers.
      In particular, it is hypothesized that if smoking cessation is of benefit for
      work attendance, the incidence of absence should be inversely related to the
      amount of time elapsed since smoking cessation. METHODS: A multivariate logit
      model of absence incidence is proposed which includes variables measuring the
      amount of time since smoking cessation. This model is then estimated using data
      collected from a sample of 4,812 ex-smokers as part of the 1989/1990 Australian
      National Health Survey. RESULTS: The estimated coefficients indicate that the
      probability of absence among ex-smokers is highest for those who only stopped
      smoking in the past year and progressively falls with the number of years since
      smoking cessation, with persons who last smoked at least 20 years ago found up to
      4.5 times less likely to be absent from work than persons who ceased smoking
      during the previous year. CONCLUSIONS: Smoking cessation is not only associated
      with improved health outcomes, but also with improved behavioral outcomes, such
      as increased work attendance. However, such improvement is observed only over
      relatively long periods of time.

PMID- 8524731
TI  - [The assessment of the noise factor and the state of the auditory analyzer in
      workers in metal rolling production].
AB  - At main workplaces in F. "Stomana" (Pernik City) sorting and sheetrolling works,
      measurements and evaluation of the noise factor were carried out, and hearing
      sensitivity of workers was investigated in 229 subjects of mean age 36.1 +/- 9.8
      years and mean occupational experience 9.7 +/- 7.4 years. Findings at workplaces
      indicated presence of noise of excessive equivalent levels and pulsing nature
      varying in degrees. Hearing thresholds for 4 and 6 kHz and average speaking
      frequency were elevated, and the proportion of subjects with hearing threshold
      above 30 dB for all frequencies tested was larger among the job groups of roller
      workers, furnace men, cutters, crane workers, markers, packers, quality control
      surveyors, and dispatchers as compared to subjects working at lower noise levels
      or exposed for shorter times to intense noise, notably, operators, fitters,
      welders, electrotechnicians. Regression analysis revealed the dynamics of change
      in hearing sensitivity to be more closely related to age than to duration of
      occupational experience.

PMID- 8524732
TI  - [The effect of different masking noises on psychophysiological tasks].
AB  - This paper describes experimental investigations aimed at clarifying the
      influence of wide-range (white), pulsed and interrupted noise with intensities
      Lequ 60 and 90 dB (A) on some psychophysiologic characteristics of problem
      solving. Physiologic indicators were recorded: pulse rate and variance, breathing
      rate and variance, vascular tone, ets. Psychologic problems to be solved modeled
      various features of operator activities, including: performing mathematical
      computations at a given rate; a test involving information processing; a compound
      option problem offered by Piotkovski's apparatus. Statistical data treatment (t
      test of Student and Fisher, and monofactorial dispersion analysis) indicated the
      masking effect of noise to be more marked in dealing with psychophysiologic
      problems relating to operative memory. From the physiologic parameters tested,
      most informative proved to be the changes occurring in peripheral circulation,
      notably, the rise in vascular tone to peripheral vessels.

PMID- 8524733
TI  - [Trends in the joint work of the National Center for Hygiene and the
      epidemiological hygiene inspectorates in the field of communal hygiene].
AB  - Based on cardinal problems of medical prevention, the author formulates priority
      lines of action for the country's health structures in the field of community
      health, emphasizing areas for interaction between the National Center of Hygiene
      and Hygiene-and-Epidemiology Inspectorates across the country. According to the
      author, priority problems necessitating collaborative efforts between the
      National Center of Hygiene and HEIs throughout the country should be focused on
      the following areas: updating sanitary legislation; environmental monitoring,
      including community and territorial planning; health risk assessment; development
      of an efficient health-information system concerning environment and health;
      manpower training; and ecologic education of the public. Collaboration also needs
      to cover joint implementation of projects at international collaboration level
      along the lines of the World Health Organization, the PHARE programs, etc. The
      priorities referred to also reflect the conception of medical prevention
      functions in the area of community health.

PMID- 8524734
TI  - [The effect of different types of music on the perception of speech information].
AB  - Under experimental conditions, the masking effect of three types of music and of
      "white" masking noise was studied using a special speech-audiometric test (L.
      Tsaneva 1978, 1993). The signal-to-noise relation was found to be the most
      significant factor affecting spoken information perception, regardless of the
      type of music used as masking agent (level of correlation coefficients, jR =
      0.89). The types of music used (modern, classical, playback) showed no
      appreciable differences in masking, remaining at the same time stronger masking
      factors compared to "white" noise. Conclusions were made as to hygienic-ergonomic
      aspects to be considered for intensity of musical programs in conforming with
      pertinent standards.

PMID- 8524735
TI  - [The assessment of the occupational risk to workers in electric steel
      production].
AB  - These studies, centering on occupational environmental factors, biologic
      monitoring, and toxicodynamic investigations, involved a total of 105 workers
      distributed into eight job groups, who were 45 years, of age on the average and
      had from 5 to 10 years of special occupational experience at "Electrosteel"
      Works. Evidence was obtained for presence of unfavorable microclimate conditions,
      elevated equivalent levels of noise, excess of general and local vibrations,
      exposure to manganese aerosols, carbon monoxide, and nitrogen oxides; some of the
      subjects and deviations in hepatic status and connective tissue. Job groups found
      to be at risk were those of steel founders, crane workers, and pourers.

PMID- 8524736
TI  - [The assessment of arsenic exposure in copper smelting].
AB  - The arsenic exposure in the main departments and occupational groups of the
      copper smelter in Pirdop has been estimated in the present study. The contents of
      arsenic is measured in the air and in biological samples--urine and nails. At
      most of the workplaces the time-weighted average (TWA) concentrations do not
      exceed the threshold limit value (0.05 mg/m3). The maximum TWA level is about
      three times higher. The intake of arsenic is significantly increased in almost
      all observed occupational groups. However, the excretion of only 8% of the
      workers is higher than the maximum background level (100 micrograms/l). The
      estimated degree of exposure corresponds to a low health risk. Some of the most
      heavily exposed occupational groups may be expected to reach higher levels of
      intake and health risk.

PMID- 8524737
TI  - [The toxic hygiene problems of workers in the Dinamik automobile tire plant in
      Sofia].
AB  - Toxic hygienic investigations were carried out involving a representative group
      of 131 workers (50 females and 81 males) distributed into three main workshops-
      preparatory, confection, and vulcanization--at "Dynamic" automobile tire plant in
      Sofia. The majority of male and female workers were in the age range beyond 40
      years, having a general occupational experience in excess of 10 years and
      specialized occupational experience from 10 to 20 years or more. The chemical
      hazard was among the leading ones in the occupational environment, differing in
      nature according to the technologies used. Included were various chemical
      substances and compounds: synthetic rubbers, fillers (soot, chalk, kaolin);
      softeners (mazut, paraffin, etc.); accelerants (mercaptothiazoles--captax and
      altax); dithiocarbamates (thiuram); vulcacides (diphenylguanidine); antiwear
      agents (antioxidants and antiozonators-isopropyl-phenyl-paraphenylene diamine,
      naphthyl-beta-naphthylamine); antiaccelerants (phthalic anhydride, ets.); organic
      solvents and others. The indicated chemical substances and compounds, though
      often found at concentrations below the mean-shift MACs, do produce health
      impacts by virtue of prolonged and combined exposures. Use was made of the
      questionnaire method. Also, hematologic, clinical laboratory, and toxic chemical
      testing was performed. Findings pointed to changes in hemopoiesis, deviations in
      hepatic functional state, while sulfate and glucuronide values confirmed the
      workers' high exposures.

PMID- 8524738
TI  - [The cytogenetic effects (the frequency of micronuclei) in lymphocyte cultures
      from the peripheral blood of workers in automobile tire manufacture].
AB  - At the Preparatory Workshop of the Plant for Automobile Tires (PAT), Sofia,
      complex investigations were undertaken to reveal possible genotoxic exposure. The
      studies included chemical analyses for levels of identifiable human carcinogens
      in the occupational ambient air (benz(a)pyrene, mineral oils, 2-naphthylamine);
      special techniques--questionnaire investigations and cytogenetic analysis by
      cytokinesis-block micronucleus method in peripheral lymphocyte cultures from 23
      workers in occupational groups at risk; and urinalysis for contents of
      mercapturic acids. An out-of-house control group of 13 nonexposed subjects was
      concurrently investigated. For contents of benz(a)pyrene and mineral oils
      exceeding 2.5 to 3.5 times the respective occupational environment MACs, evidence
      from cytogenetic analysis showed substantial, 4-fold, increase in indexes of
      genotoxic impairment (frequency of micronucleated-binucleated lymphocytes, number
      of micronuclei per 1000 binucleated lymphocytes) in the workers investigated.
      These results are an indicator of genotoxic exposure and point to an increased
      potential risk of cancer development in the group of workers studied.

PMID- 8524739
TI  - [An experimental study of the effect of an artichoke preparation on the activity
      of the sympathetic-adrenal system in carbon disulfide exposure].
AB  - Artichoke, a new Bulgarian preparation based on the plant Cynara scolymus, was
      tested for influence on sympatho-adrenal system (SAS) activity in experimental
      inhalation exposure to carbon disulfide. This chronic (six-month) inhalation
      experiment was done on Wistar albino rats of either sex. Activity of SAS was
      assessed through excretion of noradrenalin and adrenalin. Findings indicated a
      phasic SAS response depending on concentration and duration of carbon disulfide
      exposure. With exposure to 30 mg.m3, SAS activity was observed to decrease in the
      second month, followed by increase in the fourth and sixth months. With exposure
      to 300 mg.m3, SAS activity was elevated over the whole period of study. Under the
      influence of the preparation artichoke at dosage 200 mg.kg-1, catecholamines,
      increased by carbon disulfide exposure, returned to normal. This trend was more
      marked for noradrenalin.

PMID- 8524740
TI  - [The determination of the maximum permissible noise level for areas and zones
      incorporating facilities requiring enhanced noise protection].
AB  - Noise, a stressogenic factor adversely affecting the body, is subject to
      monitoring and control, notably, at sites where health considerations impose a
      more rigorous acoustic regimen. Where systematic and ubiquitous excesses over
      admissible noise level occur in an urban environment, a special case of health
      impact is that produced upon an inpatient's course of recovery from illness. This
      paper presents evidence from a survey of mean excesses over HEI-regulated noise
      standards for zones enclosing 16 Sofia inpatient facilities. The procedure used
      to determine and map mean excesses in cities has been made available to the
      preventive network of local HEIs countrywide; however, it still has not been put
      into practice everywhere. This renewed presentation, it is hoped, should
      contribute to recognizing its necessity and making use of the technique. The most
      frequently encountered excesses over the admissible noise level were within the
      range 15-20 dB A. For districts incorporating hospital institutions, this
      acoustic situation may be qualified as not only inadequate to requirements but
      also as generating a health risk for vulnerable population groups. Clearly, the
      noise regimen observed in the surveyed zones in an environmental physical hazard
      hindering the process of recovery from illness--with all health, social, and
      economic negative effects entailed.

PMID- 8524741
TI  - [The basic parameters affecting the taking of air samples by concentration
      methods--the absorption method].
AB  - The role of major factors influencing sampling effectiveness if using fluid
      absorbing media for studies of air pollution was investigated. The decisive role
      proved to be played by volatility of the substances used. Highly effective
      sampling was achieved with low volatility substances, or when chemical
      interaction between the absorbing medium and the substance to be studied resulted
      in compounds of low volatility.

PMID- 8524742
TI  - [The basic parameters affecting the taking of air samples by concentration
      methods--the adsorption method].
AB  - To obtain reliable results from examination of air sampled onto adsorbents, it is
      necessary to define the latters' basic parameters: adsorption capacity under
      sampling conditions, and analytical recovery in separating substances from the
      sampling medium in view of the next step, analysis. Using a system specially
      developed for the purpose, the above parameters were tested with five types of
      activated carbon.

PMID- 8524743
TI  - [The personal exposure of workers in the manufacture of xylenes--in Burgas (the
      Neftokhim firm)].
AB  - Individual exposures were qualitatively and quantitatively characterized for
      "Xylols" manufacturing workers. To this end, air sampling was performed from the
      breathing zones of workers occupied at varying jobs, covering a representative
      group of 29 subjects; for comparison, 17 stationary samples were taken from work
      places at the same facility. A gas chromatographic procedure specially developed
      for the purpose was used for identification and quantitative analysis of the
      substances recovered. Fatty and aromatic hydrocarbons were found to be the
      principal pollutants of the occupational atmosphere. The leading pollutant proved
      to be benzene, by virtue of its high toxicity and relatively high levels (around
      and above its MAC).

PMID- 8524744
TI  - [A spectrophotometric method for controlling the concentration of aromatic
      hydrocarbons in the calibration of indicator tubes].
AB  - A modified spectrophotometric method is proposed for monitoring air
      concentrations of xylol, toluol, benzol, ethylbenzol, and chlorobenzol. The
      method has been introduced to control concentrations of the above aromatic
      hydrocarbons in calibrating indicator tubes, manufactured by the firm "Hygitest",
      and complies to the specific requirements for that process. There are possible
      applications in other areas, but further studies would be needed. The proposed
      method satisfies accuracy and reproducibility requirements. It successfully
      replaces the more laborious gas chromatographic and IR spectroscopic methods.

PMID- 8524745
TI  - [The neurological screening of workers in the manufacture of copper and aluminum
      rolled wire].
AB  - The screening of the nervous system function in 42 workers of copper rolled wire
      [correction of valzdrat] production and in 34 workers of aluminium rolled wire
      [correction of valzdrat] production was performed in 1992 and 1993 too; 52
      healthy military men were investigated as control group. Target neurological
      anamnesis, internal and detailed neurological status were carried out. Symptoms
      of radiculopathy, neurasthenic syndrome and signs of generalized neurovegative
      dystonia were established in both studies--1992 and 1993. It is suggested that an
      further detailed investigation (including psychometric tests) is needed to verify
      of refute the neurotoxic effect of copper and aluminium.

PMID- 8524746
TI  - [Elements in the communication and social contacts of chronically ill and healthy
      pupils in the upper school ages (a questionnaire study)].
AB  - This inquiry, carried out in the city of Sofia, covered 247 students with chronic
      affections and 389 healthy students in the age range 15-18 years. As shown by the
      results, both student groups gave preference to an environment outside the home
      and school: they like it better to be among friends, in a friendly circle. In
      case problems arise, the ambiance of friends is again leading: 16.6% prefer to
      "share with friends", and only 7.8% "turn for advice to parents". The chronically
      ill were found significantly more often (p < 0.001) to feel "isolated" and
      "lonely" among their peers: their social communicability and, respectively, their
      level of adaptation to an adult environment was negatively affected.

PMID- 8524747
TI  - [The cartographic method in hygiene research].
AB  - Certain properties of the map as a model are briefly examined. Use of the
      cartographic model in hygiene largely depends on space characteristics of the
      events and processes being studied. Hygiene as a science introduces into the map
      new, specific contents and a methodology that includes analysis and evaluation of
      mapped processes and events from the viewpoint of their impact upon people's
      health. Based on the events and processes imaged, a concise classification of
      maps used in hygiene is given.

PMID- 8524748
TI  - [An experimental study of the effect of vanadium on enzyme indices in chronic
      oral exposure].
AB  - Changes in selected enzyme parameters were followed in a one year-long
      toxicologic experiment on albino rat males given vanadium by mouth at either of
      two dosages: 0.005 mg/kg b.w., which is the equivalent of the regulated level for
      1st category drinking water, or 0.01 mg/kg, i.e., twice the safety standard. The
      endpoints measured included: free sulfhydryl groups in blood serum, heart, and
      liver; cholinesterase and creatine kinase activities in blood serum; catalase
      activity in blood; and cytochrome oxidase activity in liver and heart. Chronic
      oral exposures to vanadium 0.01 mg/kg and, to a lesser extent, 0.005 mg/kg were
      observed to produce disturbances in redox processes and tissue respiration. The
      evidence from this study should be taken into consideration when regulating
      vanadium levels in drinking water from a hygiene standpoint.

PMID- 8524749
TI  - [The joint activities of the National Center for Hygiene, Medical Ecology and
      Nutrition and the epidemiological hygiene inspectorates in 1993 and 1994].
AB  - Priority problems for collaboration between the NHMEN Center and HEIs over the
      period 1993-1994 are pointed out: updating sanitary legislation; monitoring the
      environment, including community and territorial planning; assessing health risk;
      manpower training; developing an efficient health-information system; and public
      education in ecology. A detailed analysis is presented on interactions between
      the NHMEN Center and HEIs aimed at solving the above problems by implementing
      tasks pertaining to scientific research, applied research, expertization,
      training, and methodological activities.

PMID- 8524750
TI  - [An occupational physiology study at the Asarel Mining and Milling Works. The
      evaluation of the work load in the basic jobs in an open-pit mine].
AB  - This occupational physiology study was undertaken within a wider applied-research
      framework designed to evaluate the occupational environment and its impact on
      workers at "Asarel" Mining and Milling Works. Analysis of activities showed
      physical effort (dynamic and static) to be the major problem at the open pit,
      though varying in extent between jobs (most prominent for blasters and
      bulldozerists). Nervous/emotional strain, while not leading, was sustained mostly
      by diggers and blasters, followed by drivers. Organization of work (shift
      regimen, no regulated breaks, stepwise schedule of days off work) was hardly
      appropriate and did not allow for recovery. Interviewed workers qualified working
      conditions as extremely unfavorable; they disapproved with the physical factors
      of the occupational environment, the workplace, the state of machines and
      devices, and remuneration for work performed. Exertion from work, assessed by
      pulse rate and energy expended, was moderate for most activities of diggers,
      drivers, and drillers. The burden of physical effort was great for blasters at
      the open pit and for diggers and drillers performing extra repair operations
      (pulse rate, 100-110 strokes/min; energy expended, 5.2-5.5 Kcal/min). Hardest and
      least attractive was the work of blasters at stores for explosive materials
      (pulse rate, 120-141 strokes/min; energy expended, 5.5-6.5 Kcal/min). These
      adverse factors of labor activities might produce a negative impact on worker
      health and performance, leading to occupational impairment of their
      musculoskeletal system, to labor-related disorders of their cardiovascular and
      nervous systems, etc. Preventive measures are thus necessary to limit physical
      exertion, optimize the work-and-rest regimen; also, there is a need for
      conducting pertinent preventive medical examinations, providing social measures
      (conditions for transportation, rest, nutrition, sports), etc.

PMID- 8524751
TI  - [An occupational physiology study at the Asarel Mining and Milling Works-
      screening for risk factors of the cardiovascular system in workers in an open-pit
      mine].
AB  - It was the purpose of this study to define the frequency of occurrence of a
      number of individual and occupational factors contributing to development of
      arterial hypertension in "Asarel" MMW open-pit workers. The investigated subjects
      numbered 36 and ranged in age from 22 to 55 years (average, 36 +/- 1.9 years).
      The jobs represented included mainly: diggers, bulldozers, driver, drillers,
      blasters, road-service workers, electric and mechanic fitters. Endpoints measured
      and evaluated included: arterial blood pressure, pulse rate, biometric
      characteristics (age, occupational experience, body height and weight), common
      risk factors, such as family antecedents, cigarette smoking, alcohol consumption,
      level of physical activity at and off work, etc. For this sample of open-pit
      workers, findings indicated a relatively high incidence of hypertension (28% of
      subjects). The level of arterial hypertension consistently correlated with worker
      age, length of occupational experience, and body weight. There was high
      prevalence of cardiovascular risk factors: alcohol consumption, family history,
      cigarette smoking, use of salty foods, overweight. The observed changes in the
      cardiovascular system and high prevalence of risk factors point to the necessity
      of taking specific medical prevention measures. These have been taken into
      consideration in designing the overall program of upgrading work conditions and
      organization, as well as improving the style of life of "Asarel" MMW workers.

PMID- 8524752
TI  - [Age-related transfer coefficients of the basic indices of cardiac variance].
AB  - This study was concerned with the relationship of changes in cardiac variance to
      age. A total of 518 subjects were involved. The following indicators of ACV
      (analysis of cardiac variance) were investigated: mean--mean value of successive
      cardiac intervals, SD--standard deviation of mean value of cardiac intervals (R
      R), AMo--amplitude of the mode, HI--homeostatic index, Pt--spectral power of R-R
      related to thermoregulation, Pr--spectral power of R-R related to respiration,
      IBO--index of centralization. For each one of these ACV indicators, a
      mathematical expression of its relationship to age was specified. The
      coefficients obtained from the indicated expressions of the relationship "age-to
      ACV indicators" represent transfer coefficients for the particular measured
      quantities. Their methodological importance lies in the fact that through them it
      becomes possible to make age corrections of ACV indicator figures for the purpose
      of comparing individual subjects or groups of subjects. These coefficients help
      to establish nomograms for the particular age ranges.

PMID- 8524753
TI  - [Changes in the status of the adaptation of workers at the television relay
      station on top of Botev Peak].
AB  - The state of adaptation of subjects (numbering 17) occupied at Botev Peak TV
      relay station and thereby exposed to nonionizing radiations--electromagnetic
      fields (EMF)--was monitored by following changes in analysis of cardiac variance
      (ACV) indicators. In addition to these, other physiologic indicators studied were
      systolic and diastolic blood pressure, as well as psychologic indicators,
      notably, psychosomatic complaints as early manifestations of disturbance in the
      state of adaptation. Data from the group of subjects studied were compared to
      those of a control group whose working conditions involved no EMF exposure. This
      comparison, based on ACV indicators (mean--mean value of successive cardiac
      intervals, SD--standard deviation of mean value of cardiac intervals (R-R), AMo-
      amplitude of the mode, SI, ABI, HI--homeostatic index, CP--classification
      parameter, IC), psychosomatic complaints, systolic and diastolic blood pressure,
      provided no evidence of reduction of adaptive reserves or deterioration of
      somatic and mental health state in occupationally exposed workers at Botev Peak
      TV relay station.

PMID- 8524754
TI  - [The correlations between psychological indices and cardiac variance].
AB  - Correlative links between psychologic and psychologic indicators were studied in
      subjects occupied either in airline transportation or in the chemical industry.
      Investigations covered three groups of persons: managers of airline traffic (57
      subjects); workers at "Vratsa" Chemical plant (14 subjects); and operators at
      "Vratsa" Chemical plant (14 subjects). The psychologic parameters measured
      included indicators of cardiac variance: mean--mean value of successive cardiac
      intervals, SD--standard deviation of mean value of cardiac intervals (R-R), AMo-
      amplitude of the mode, HI--homeostatic index, Pt--spectral power of R-R related
      to thermoregulation, Pp--spectral power of R-R related to respiration, IBO--index
      of centralization; psychologic parameters included: extrovertiveness,
      introvertiveness, neuroticism, psychoticism, interpersonality conflicts, self
      control, social support, self-confidence, work satisfaction, psychosomatic
      complaints. There was evidence of significant and highly significant correlative
      links between indicators of cardiac variance and psychologic indicators. There
      thus appeared to exist certain relationships between the psychologic and
      psychologic levels during lengthy stressful occupational exposure.

PMID- 8524755
TI  - [Chronic occupational stress and the cardiovascular risk in teachers].
AB  - Age changes in arterial pressure (AP) and incidence of arterial hypertension
      (AH), as well as probability of developing IHD, were compared between school
      teachers and a control group sustaining no excessive occupational stress. The
      investigated teachers, numbering 168, were from Sofia public schools and
      technical schools. The control group consisted of 103 women: office employees,
      designers, research workers, etc. Findings indicated teachers to have a closer
      age relationship to AP level, compared to controls. Considerable increase in
      systolic AP was observed after 45 years of age, and there was a significant
      difference between the first and the second halves of the 4th decade. Diastolic
      AP was also higher in teachers than in controls. Duration of teaching experience
      proved to be strongly correlated with systolic and diastolic AP levels (r = 0.56,
      p < 0.001; and r = 0.50, p < 0.001). Beyond 40 years of age, teachers showed a
      high incidence of AH, 31%. The group as a whole was at high cardiovascular risk.

PMID- 8524756
TI  - [The prevalence of the burnout syndrome in the personnel of children's
      institutions].
AB  - It was the purpose of this study to investigate the occupational "burn out"
      syndrome in personnel catering for children at nurseries and mother-and-child
      homes (MCH). Burnout as consequence of unsurmounted prolonged occupational stress
      in characterized by a growing sense of professional exhaustion, indifference to
      the ones entrusted, decreased reliance on one's own professional skills, loss of
      motivation for work. Using Maslach's questionnaire, the extent of experienced
      burn out was defined for 180 subjects from a variety of child establishments.
      Results indicated prevalence of early stages of the syndrome, which was
      significantly higher at MCHs, reflecting differences in workloads. Clearly
      manifested symptoms were noted in 30% of investigated subjects. The burn out
      state of personnel at child establishments was primarily characterized by
      decrease in the sense of competence and performance. Since a marked burn out
      syndrome in attending personnel carries a risk for the general development of
      children, there is a need for recognizing the problem and defining
      responsibilities for relevant prevention.

PMID- 8524758
TI  - [Risk factors and their significance in the development of diffuse forms of
      tuberculosis in adolescents].
AB  - Follow-up study of 106 adolescents with advanced and complicated tuberculosis
      revealed causes and risk factors of the severe disease: late detection and
      treatment, massive infection, inadequate initial treatment, drug resistance of M.
      tuberculosis, poor tolerance of chemotherapy, presence of associated diseases and
      chronic infection foci, harmful habits. Of importance is also age-sex factor,
      absence of BCG revaccination, low quality of preventive, diagnostic and
      therapeutic service, inadequate hygienic education of adolescents.

PMID- 8524757
TI  - [Prevalence and clinical aspects of tuberculosis in children and adolescents in
      the Primorsk Region].
AB  - The analysis of epidemiological trends in tuberculosis registered for 13 years in
      children and adolescents living in the Primorsky Region of Russia discovered a
      trend to an increase of its incidence rate especially in girls and rural
      population. The morbidity of children aged 4-6, schoolchildren and adolescents
      aged 17 reached in 1993 137, 22.9 and 62.8 per 100,000 people, respectively.
      Tuberculosis of the respiratory organs occurred most frequently. In children
      tuberculosis of intrathoracic lymph nodes was encounted in 88.2% of new cases, in
      adolescents focal and infiltrative forms were recorded in 27 and 50.8%,
      respectively. Worsening of ecological and social situation in the region affected
      negatively immunological indices in the young population. This necessitates
      urgent measures to control spreading tuberculosis in the Far East of Russia.

PMID- 8524759
TI  - [Several characteristics of the pulmonary tuberculosis course in patients with
      different degree of diabetes mellitus compensation].
AB  - Symptoms of pulmonary tuberculosis were assessed clinically, roentgenologically
      and using laboratory tests in 34 new cases of tuberculosis with diabetes mellitus
      (DM) compensated in different degree. A correlation was found between the degree
      of DM compensation and severity of the specific process. Patients with a higher
      level of glycosylated hemoglobin had more serious intoxication, more advanced
      process, were prone to destruction, more resistant to treatment, discharged
      bacteria more frequently. Pulmonary tuberculosis in the presence of DM runs more
      unfavorably in less compensated patients.

PMID- 8524760
TI  - [Significance of the functional state of blood phagocytes in the choice of
      optimal regime of EHF therapy of patients with pulmonary tuberculosis].
AB  - A trial entered 136 patients with active tuberculosis of the lungs. 86 patients
      received conventional chemotherapy and a course of microwave therapy. Control
      patients received chemotherapy alone. Phagocyte cell viability and NB-test served
      as assessment laboratory criteria. Millimetric waves in the treatment of
      pulmonary tuberculosis potentiate the treatment efficacy documented as more rapid
      infiltration resolution and cavern closure through the mechanism of normalization
      of phagocyte cell function. The choice of wave length is principal: 5.6 mm waves
      affect phagocyte function negatively, 6.4 mm waves produce more significant
      positive effect in young patients with new local lesions while 7.1 mm waves in
      older patients and in severe involvement. In vitro radiation of the patients'
      blood using different wave lengths and subsequent performance of NB-test provides
      objective information for choice of optimal treatment regimen.

PMID- 8524761
TI  - [Concept of organization of tuberculosis prevention services in Russia].
AB  - Reduced financing of antituberculosis service calls for new organizational
      measures aimed at more efficient activity of antituberculous institutions.
      Different forms of the service depending on local needs and resources, special
      programs are introduced.

PMID- 8524762
TI  - [Results of the treatment of patients with recurrence of pulmonary tuberculosis
      with different types of haptoglobin].
AB  - Phenotyping of haptoglobin Hp has been performed in 74 patients with recurrent
      tuberculosis. In patients with recurrences homozygous variant of phenotype Hp 2-2
      occurs more frequently, while heterozygous variant Hp 2-1 less frequently. In
      carriers of phenotype Hp 2-2 recurrent tuberculosis is found more frequently,
      runs more seriously, heals in the presence of destruction less actively. These
      reasons underlie high incidence of chronic forms. Subjects with Hp 2-2 (55.3%)
      need special attention in conduction of recurrence prophylaxis. In carriers of
      phenotype Hp 2-1 pulmonary tuberculosis relapses less frequently, runs less
      seriously, resists to treatment rarely.

PMID- 8524763
TI  - [Ways to expand indications for surgical treatment of patients with fibro
      cavernous pulmonary tuberculosis].
AB  - The authors present original operative techniques developed in the Novosibirsk
      Tuberculosis Research Institute for management of fibro-cavernous pulmonary
      tuberculosis. These include: a 4-5-rib variant of osteoplastic thoracoplasty as
      an independent intervention and as a stage followed by pulmonary resection,
      atypical extrapleural pneumolysis with open tamponade followed by local
      thoracoplasty. A complex of combined surgical adjuvant procedures comprises
      extrapleural pneumolysis with open tamponade, dissection of cavernous part of the
      lung prior to selective thoracoplasty. Indications to the use of the above
      techniques are provided. Their use in addition to conventional interventions
      gives one more chance of cure in fibro-cavernous tuberculosis of the lungs.

PMID- 8524764
TI  - [Immediate and long-term results of reconstructive surgery of the bronchi].
AB  - Bronchial plastic reconstruction has been performed in 136 patients aged 8-82. Of
      them 86, 23, 1, 6, 13, 6, 1 had cancer, carcinoid, sarcoma, benign tumor,
      nonspecific stenosis, post-tuberculous stenosis, traumatic detachment of the main
      bronchus, respectively. The patients underwent: lobectomy (101 operations),
      bilobectomy (24 operations), bisegmental bronchial resections (2 operations),
      isolated bronchial resections (9 operations). An original technique of narrowing
      of the central stump in circulatory bronchial resections is described. Neither
      postoperative complications in anastomoses nor lethal outcomes were recorded. In
      all cases of nontumor stenosis and benign tumors functional benefits were
      achieved. A 5-year survival of cancer patients reached 66.7%. The procedures and
      surgical outcomes are discussed.

PMID- 8524765
TI  - [Comparative characteristics of intrathoracic lymph node coniotuberculosis of
      occupational and non-occupational etiology].
AB  - 263 patients with coniotuberculosis of the intrathoracic lymph nodes were
      compared clinically according to whether they were or not at 0ccupational risk of
      silicosis. Patients exposed to quartz dust had some special morphological picture
      of affected lymph nodes: periadenitis, dust caseosis and tubercula in the
      presence anthracosilicosis sclerosis. Silicotuberculous broncho-adenitis in
      silicosis patients is characterized by solitary lesions of the lymph nodes,
      bronchi, rare dissemination to the lungs. Coniotuberculous broncho-adenitis in
      elderly subjects arises in the result of occupation-unrelated accumulation in the
      lymph nodes of coal and quartz dust and runs chronically. Unless the disease is
      controlled early and actively, it may generalize and aggravate with perforation
      in the bronchi, vessels and esophagus. Profuse hemorrhage, caverns, atelectasis
      are also possible.

PMID- 8524766
TI  - [Prevalence of nonspecific pulmonary diseases and their clinical course in rural
      inhabitants of Uzbekistan].
AB  - The authors point out high prevalence of nonspecific pulmonary diseases which
      varies from region to region. The latter were characterized by intensive
      application of pesticides or were located near the Aral lake. The patients
      frequently develop deforming bronchitis with severe affection of bronchial
      architectonics and morphology of pulmonary tissue responsible for persistent
      obstructive-restrictive disorders and hemodynamic shifts. Patients living in the
      above regions have compromised immunity and hormonal status reflecting impairment
      of adaptation-compensation relationships.

PMID- 8524767
TI  - [Morphological features of tissue reactions in combined treatment of experimental
      tuberculosis induced by xenobiotics].
AB  - The trend to aggravated running and contribution of air pollution of large
      industrial centers with polycyclic aromatic hydrocarbons (PAH) to tuberculosis
      onset and progress dictate the necessity of the search for new treatment methods.
      The authors made an attempt to treat experimental tuberculosis with sodium
      glutamate and isoniazide under chronic exposure to PAH dust. Sodium glutamate
      especially in combination with isoniazide produces a good effect enhancing
      granulomatous reactions fibroplastic processes in the foci of specific
      inflammation. Sodium glutamate is thought an effective pathogenetic treatment of
      tuberculosis.

PMID- 8524768
TI  - [Rapid isolation of Mycobacterium tuberculosis by chromatography and mass
      spectrometry selected-ion monitoring].
AB  - The method employs identification of M. tuberculosis marker, tuberculostearinic
      acid. Bacterial culture and sputum from tuberculous and nontuberculous pulmonary
      disease patients were examined. The results of bacterial and chromatic mass
      spectrometry methods in tuberculous patients proved identical. The latter
      technique is highly sensitive and provides quick results.

PMID- 8524769
TI  - [Use of polarization microscopy in the determination of activity and differential
      diagnosis of pulmonary tuberculosis].
AB  - 45 patients with pulmonary tuberculosis, 15 patients with acute pneumonia and 15
      healthy controls were examined using polarization microscopy of blood serum and
      blood serum + tuberculin. The serum from healthy subjects contains optically
      active structures, while that from patients has also pathological structures.
      Frequency of detection, quantitative and qualitative composition of pathological
      structures in tuberculosis are related to the disease phase and decline with the
      activity inhibition. Examination of native serum is not able to distinguish
      specific from nonspecific processes in the lungs. The addition of tuberculin to
      native serum helped detect subclinical tuberculosis. Polarization microscopy of
      native serum is recommended for control of pulmonary tuberculosis and treatment
      efficacy, modification with tuberculin may be used as an additional test for
      determination of the disease activity and for differential diagnosis with acute
      pneumonia.

PMID- 8524770
TI  - [Morphological evaluation of structural changes in the tracheal wall at the site
      of braided and monofilament sutures in experimental animals].
AB  - To select the most adequate suture material for tracheal surgery the authors
      studied tissue specimens of tracheal anastomoses from 18 guinea pigs. Scar
      replacement of the cartilage plate occurred more frequently in monofilament
      prolene suture compared to braided vicryl. Tracheal wall structural changes were
      related to rigidity of the suture material. The rigidity was higher in
      monofilament material and increased with the filament thickness.

PMID- 8524771
TI  - [One-hour lecture as a method of increasing effectiveness of teaching at the
      Phthisiatrics Department].

PMID- 8524772
TI  - [A case of hairy black tongue in phthisiatric practice].

PMID- 8524773
TI  - [Relations between pulmonary tuberculosis and chronic nonspecific pulmonary
      diseases in Blagoveshchensk medical districts].

PMID- 8524774
TI  - [Features of the course of acute pneumonia in the Amur region].

PMID- 8524775
TI  - [Prevalence of tuberculosis in the personnel of antituberculosis institutions in
      Russian Federation].
AB  - Questionnaires were distributed among all the heads of regional antituberculous
      services in Russia as to cases of tuberculosis among medical personnel in contact
      with tuberculous patients. The results of this study as well as programs to
      control tuberculosis in medical personnel are presented. Special measures of
      social support for those at occupational risk of tuberculosis are detailed.

PMID- 8524776
TI  - [Prevention of disability because of pulmonary tuberculosis].

PMID- 8524777
TI  - [Contingents of IIIA groups in the dispensary follow-up of children].
AB  - 51 case histories of children with new-onset inactive specific lesions in
      thoracic lymph nodes and the lungs in the form of calcinates have been analyzed.
      The authors come to the conclusion that late diagnosis of tuberculosis in
      children is related to difficulties in diagnosis of minor thoracic tuberculosis
      in infiltration phase, insufficient diagnostic efficacy of mass tuberculin
      examinations for early primary tuberculous infection, defects in preventive
      measures (BCG vaccination, chemoprophylaxis in risk groups).

PMID- 8524778
TI  - Radial versus tangential migration of neuronal clones in the developing cerebral
      cortex.

PMID- 8524779
TI  - The histone fold: evolutionary questions.

PMID- 8524780
TI  - Uniparental inheritance of mitochondrial and chloroplast genes: mechanisms and
      evolution.
AB  - In nearly all eukaryotes, at least some individuals inherit mitochondrial and
      chloroplast genes from only one parent. There is no single mechanism of
      uniparental inheritance: organelle gene inheritance is blocked by a variety of
      mechanisms and at different stages of reproduction in different species. Frequent
      changes in the pattern of organelle gene inheritance during evolution suggest
      that it is subject to varying selective pressures. Organelle genes often fail to
      recombine even when inherited biparentally; consequently, their inheritance is
      asexual. Sexual reproduction is apparently less important for genes in organelles
      than for nuclear genes, probably because there are fewer of them. As a result
      organelle sex can be lost because of selection for special reproductive features
      such as oogamy or because uniparental inheritance reduces the spread of
      cytoplasmic parasites and selfish organelle DNA.

PMID- 8524781
TI  - Sequence verification of human creatine kinase (43 kDa) isozymes by high
      resolution tandem mass spectrometry.
AB  - Amino acid sequencing by recombinant DNA technology, although dramatically
      useful, is subject to base reading errors, is indirect, and is insensitive to
      posttranslational processing. Mass spectrometry techniques can provide molecular
      weight data from even relatively large proteins for such cDNA sequences and can
      serve as a check of an enzyme's purity and sequence integrity. Multiply-charged
      ions from electrospray ionization can be dissociated to yield structural
      information by tandem mass spectrometry, providing a second method for gaining
      additional confidence in primary sequence confirmation. Here, accurate (+/- 1 Da)
      molecular weight and molecular ion dissociation information for human muscle and
      brain creatine kinases has been obtained by electrospray ionization coupled with
      Fourier-transform mass spectrometry to help distinguish which of several
      published amino acid sequences for both enzymes are correct. The results herein
      are consistent with one published sequence for each isozyme, and the
      heterogeneity indicated by isoelectric focusing due to 1-Da deamidation changes.
      This approach appears generally useful for detailed sequence verification of
      recombinant proteins.

PMID- 8524782
TI  - Identification of a hexapeptide inhibitor of the human immunodeficiency virus
      integrase protein by using a combinatorial chemical library.
AB  - Integration of human immunodeficiency virus (HIV) DNA into the human genome
      requires the virus-encoded integrase (IN) protein, and therefore the IN protein
      is a suitable target for antiviral strategies. To find a potent HIV IN inhibitor,
      we screened a "synthetic peptide combinatorial library." We identified a
      hexapeptide with the sequence HCKFWW that inhibits IN-mediated 3'-processing and
      integration with an IC50 of 2 microM. The peptide is active on IN proteins from
      other retroviruses such as HIV-2, feline immunodeficiency virus, and Moloney
      murine leukemia virus, supporting the notion that a conserved region of IN is
      targeted. The hexapeptide was also tested in the disintegration reaction. This
      phosphoryl-transfer reaction can be carried out by the catalytic core of IN
      alone, and the peptide HCKFWW was found to inhibit this reaction, suggesting that
      the hexapeptide acts at or near the catalytic site of IN. Identification of an IN
      hexapeptide inhibitor provides proof of concept for the approach, and, moreover,
      this peptide may be useful for structure-function analysis of IN.

PMID- 8524783
TI  - In vitro trans-splicing in Saccharomyces cerevisiae.
AB  - The interactions established at the 5'-splice site during spliceosome assembly
      are likely to be important for both precise recognition of the upstream intron
      boundary and for positioning this site in the active center of the spliceosome.
      Definition of the RNA-RNA and the RNA-protein interactions at the 5' splice site
      would be facilitated by the use of a small substrate amenable to modification
      during chemical synthesis. We describe a trans-splicing reaction performed in
      Saccharomyces cerevisiae extracts in which the 5' splice site and the 3' splice
      site are on separate molecules. The RNA contributing the 5' splice site is only
      20 nucleotides long and was synthesized chemically. The trans-splicing reaction
      is accurate and has the same sequence, ATP, and Mg2+ requirements as cis
      splicing. We also report how deoxy substitutions around the 5'-splice site affect
      trans-splicing efficiency.

PMID- 8524784
TI  - A protein that interacts with members of the nuclear hormone receptor family:
      identification and cDNA cloning.
AB  - In search of proteins which interact with activated steroid hormone receptors, we
      screened a human liver lambda gt11 expression library with the glucocorticoid
      receptor. We identified and cloned a cDNA sequence of 1322 bp that encodes a
      protein of 274 aa. This protein consists predominantly of hydrophilic amino acids
      and contains a putative bipartite nuclear localization signal. The in vitro
      translated receptor-associating protein runs in SDS/polyacrylamide gels with an
      apparent molecular mass of 46 kDa. By use of the bacterially expressed fusion
      protein with glutathione S-transferase we have found that interaction is not
      limited to the glucocorticoid receptor but included other nuclear receptors--most
      notably, the estrogen and thyroid receptors. Binding also occurs with the
      glucocorticoid receptor complexed with the antiglucocorticoid RU 38486, with the
      estrogen receptor complexed with the antiestrogen 4-hydroxytamoxifen or ICI
      164,384, and even with receptors not complexed with ligand. Association with
      steroid hormone receptors depends on prior receptor activation--i.e., release
      from heat shock proteins. The sequence identified here appears to be a general
      partner protein for nuclear hormone receptors, with the gene being expressed in a
      variety of mammalian tissues.

PMID- 8524785
TI  - Enhanced somatic mutation rates induced in stem cells of mice by low chronic
      exposure to ethylnitrosourea.
AB  - We have found that the somatic mutation rate at the Dlb-1 locus increases
      exponentially during low daily exposure to ethylnitrosourea over 4 months. This
      effect, enhanced mutagenesis, was not observed at a lacI transgene in the same
      tissue, although the two loci respond very similarly to acute doses. Since both
      mutations are neutral, the mutant frequency was expected to increase linearly
      with time in response to a constant mutagenic exposure, as it did for lacI.
      Enhanced mutagenesis does not result from an overall sensitization of the
      animals, since mice that had first been treated with a low daily dose for 90 days
      and then challenged with a large acute dose were not sensitized to the acute
      dose. Nor was the increased mutant frequency due to selection, since animals that
      were treated for 90 days and then left untreated for up to 60 days showed little
      change from the 90-day frequency. The effect is substantial: about 8 times as
      many Dlb-1 mutants were induced between 90 and 120 days as in the first 30 days.
      This resulted in a reverse dose rate effect such that 90 mg/kg induced more
      mutants when delivered at 1 mg/kg per day than at 3 mg/kg per day. We postulate
      that enhanced mutagenesis arises from increased stem cell proliferation and the
      preferential repair of transcribed genes. Enhanced mutagenesis may be important
      for risk evaluation, as the results show that chronic exposures can be more
      mutagenic than acute ones and raise the possibility of synergism between
      chemicals at low doses.

PMID- 8524786
TI  - Identification of a Drosophila G protein alpha subunit (dGq alpha-3) expressed in
      chemosensory cells and central neurons.
AB  - We have identified another Drosophila GTP-binding protein (G protein) alpha
      subunit, dGq alpha-3. Transcripts encoding dGq alpha-3 are derived from
      alternative splicing of the dGq alpha locus previously shown to encode two visual
      system-specific transcripts [Lee, Y.-J., Dobbs, M.B., Verardi, M.L. & Hyde, D.R.
      (1990) Neuron 5, 889-898]. Immunolocalization studies using dGq alpha-3 isoform
      specific antibodies and LacZ fusion genes show that dGq alpha-3 is expressed in
      chemosensory cells of the olfactory and taste structures, including a subset of
      olfactory and gustatory neurons, and in cells of the central nervous system,
      including neurons in the lamina ganglionaris. These data are consistent with a
      variety of roles for dGq alpha-3, including mediating a subset of olfactory and
      gustatory responses in Drosophila, and supports the idea that some chemosensory
      responses use G protein-coupled receptors and the second messenger inositol 1,4,5
      trisphosphate.

PMID- 8524787
TI  - Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in
      exacerbating focal brain ischemic damage.
AB  - Focal brain ischemia is the most common event leading to stroke in humans. To
      understand the molecular mechanisms associated with brain ischemia, we applied
      the technique of mRNA differential display and isolated a gene that encodes a
      recently discovered peptide, adrenomedullin (AM), which is a member of the
      calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model
      of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression
      was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post
      MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated
      for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies
      localized AM to ischemic neuronal processes, and radioligand (125I-labeled CGRP)
      displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP
      receptors in brain cortex. The cerebrovascular function of AM was studied using
      synthetic AM microinjected onto rat pial vessels using a cranial window or
      applied to canine basilar arteries in vitro. AM, applied abluminally, produced
      dose-dependent relaxation of preconstricted pial vessels (P < 0.05).
      Intracerebroventricular (but not systemic) AM administration at a high dose (8
      nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P
      < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic
      cortical neurons, the demonstration of the direct vasodilating effects of the
      peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain
      damage suggests that AM plays a significant role in focal ischemic brain injury.

PMID- 8524788
TI  - Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA
      dependent protein kinase activity.
AB  - V(D)J rearrangement is the molecular mechanism by which an almost infinite array
      of specific immune receptors are generated. Defects in this process result in
      profound immunodeficiency as is the case in the C.B-17 SCID mouse or in RAG-1
      (recombination-activating gene 1) or RAG-2 deficient mice. It has recently become
      clear that the V(D)J recombinase most likely consists of both lymphoid-specific
      factors and ubiquitously expressed components of the DNA double-strand break
      repair pathway. The deficit in SCID mice is in a factor that is required for both
      of these pathways. In this report, we show that the factor defective in the
      autosomal recessive severe combined immunodeficiency of Arabian foals is required
      for (i) V(D)J recombination, (ii) resistance to ionizing radiation, and (iii) DNA
      dependent protein kinase activity.

PMID- 8524789
TI  - Studies of group B streptococcal infection in mice deficient in complement
      component C3 or C4 demonstrate an essential role for complement in both innate
      and acquired immunity.
AB  - Group B streptococci (GBS) cause sepsis and meningitis in neonates and serious
      infections in adults with underlying chronic illnesses. Specific antibodies have
      been shown to be an important factor in protective immunity for neonates, but the
      role of serum complement is less well defined. To elucidate the function of the
      complement system in immunity to this pathogen, we have used the approach of gene
      targeting in embryonic stem cells to generate mice totally deficient in
      complement component C3. Comparison of C3-deficient mice with mice deficient in
      complement component C4 demonstrated that the 50% lethal dose for GBS infection
      was reduced by approximately 50-fold and 25-fold, respectively, compared to
      control mice. GBS were effectively killed in vitro by human blood leukocytes in
      the presence of specific antibody and C4-deficient serum but not C3-deficient
      serum. The defective opsonization by C3-deficient serum in vitro was corroborated
      by in vivo studies in which passive immunization of pregnant dams with specific
      antibodies conferred protection from GBS challenge to normal and C4-deficient
      pups but not C3-deficient pups. These results indicate that the alternative
      pathway is sufficient to mediate effective opsonophagocytosis and protective
      immunity to GBS in the presence of specific antibody. In contrast, the increased
      susceptibility to infection of non-immune mice deficient in either C3 or C4
      implies that the classical pathway plays an essential role in host defense
      against GBS infection in the absence of specific immunity.

PMID- 8524790
TI  - A de novo missense mutation of the beta subunit of the epithelial sodium channel
      causes hypertension and Liddle syndrome, identifying a proline-rich segment
      critical for regulation of channel activity.
AB  - Liddle syndrome is a mendelian form of hypertension characterized by
      constitutively elevated renal Na reabsorption that can result from activating
      mutations in the beta or gamma subunit of the epithelial Na channel. All reported
      mutations have deleted the last 45-76 normal amino acids from the cytoplasmic C
      terminus of one of these channel subunits. While these findings implicate these
      terminal segments in the normal negative regulation of channel activity, they do
      not identify the amino acid residues that are critical targets for these
      mutations. Potential targets include the short highly conserved Pro-rich segments
      present in the C terminus of beta and gamma subunits; these segments are similar
      to SH3-binding domains that mediate protein-protein interaction. We now report a
      kindred with Liddle syndrome in which affected patients have a mutation in codon
      616 of the beta subunit resulting in substitution of a Leu for one of these
      highly conserved Pro residues. The functional significance of this mutation is
      demonstrated both by the finding that this is a de novo mutation appearing
      concordantly with the appearance of Liddle syndrome in the kindred and also by
      the marked activation of amiloride-sensitive Na channel activity seen in Xenopus
      oocytes expressing channels containing this mutant subunit (8.8-fold increase
      compared with control oocytes expressing normal channel subunits; P = 0.003).
      These findings demonstrate a de novo missense mutation causing Liddle syndrome
      and identify a critical channel residue important for the normal regulation of Na
      reabsorption in humans.

PMID- 8524791
TI  - Transport of cytoskeletal elements in the squid giant axon.
AB  - In order to explore how cytoskeletal proteins are moved by axonal transport, we
      injected fluorescent microtubules and actin filaments as well as exogenous
      particulates into squid giant axons and observed their movements by confocal
      microscopy. The squid giant axon is large enough to allow even cytoskeletal
      assemblies to be injected without damaging the axon or its transport mechanisms.
      Negatively charged, 10- to 500-nm beads and large dextrans moved down the axon,
      whereas small (70 kDa) dextrans diffused in all directions and 1000-nm beads did
      not move. Only particles with negative charge were transported. Microtubules and
      actin filaments, which have net negative charges, made saltatory movements down
      the axon, resulting in a net rate approximating that previously shown for slow
      transport of cytoskeletal elements. The present observations suggest that
      particle size and charge determine which materials are transported down the axon.

PMID- 8524792
TI  - Red/far-red and blue light-responsive regions of maize rbcS-m3 are active in
      bundle sheath and mesophyll cells, respectively.
AB  - Leaves of the C4 plant maize have two major types of photosynthetic cells: a ring
      of five large bundle sheath cells (BSC) surrounds each vascular bundle and
      smaller mesophyll cells (MC) lie between the cylinders of bundle sheath cells.
      The enzyme ribulose bisphosphate carboxylase/oxygenase is encoded by nuclear rbcS
      and chloroplast rbcL genes. It is not present in MC but is abundant in adjacent
      BSC of green leaves. As reported previously, the separate regions of rbcS-m3,
      which are required for stimulating transcription of the gene in BSC and for
      suppressing expression of reporter genes in MC, were identified by an in situ
      expression assay; expression was not suppressed in MC until after leaves of dark
      grown seedlings had been illuminated for 24 h. Now we have found that transient
      expression of rbcS-m3 reporter genes is stimulated in BSC via a red/far-red
      reversible phytochrome photoperception and signal transduction system but that
      blue light is required for suppressing rbcS-m3 reporter gene expression in MC.
      Blue light is also required for the suppression system to develop in MC. Thus,
      the maize gene rbcS-m3 contains certain sequences that are responsive to a
      phytochrome photoperception and signal transduction system and other regions that
      respond to a UVA/blue light photoperception and signal transduction system.
      Various models of "coaction" of plant photoreceptors have been advanced; these
      observations show the basis for one type of coaction.

PMID- 8524793
TI  - Isolation of virus-neutralizing RNAs from a large pool of random sequences.
AB  - RNA and ribonuclease-resistant RNA analogs that bound and neutralized Rous
      sarcoma virus (RSV) were isolated from a large pool of random sequences by
      multiple cycles of in vitro selection using infectious viral particles. The
      selected RNA pool of RSV-binding sequences at a concentration of 0.16 microM
      completely neutralized the virus. Of 19 sequences cloned from the selected pool,
      5 inhibited RSV infection. The selected RNA and RNA analogs were shown to
      neutralize RSV by interacting with the virus, rather than by adversely affecting
      the host cells. The selection of the anti-RSV RNA and RNA analogs by intact
      virions immediately suggests the potential application of this approach to
      develop RNA and RNA analogs as inhibitors of other viruses such as human
      immunodeficiency virus.

PMID- 8524794
TI  - Inducible nitric oxide synthase: identification of amino acid residues essential
      for dimerization and binding of tetrahydrobiopterin.
AB  - Nitric oxide synthases (NOSs) require tetrahydrobiopterin (BH4) for dimerization
      and NO production. Mutation analysis of mouse inducible NOS (iNOS; NOS2)
      identified Gly-450 and Ala-453 as critical for NO production, dimer formation,
      and BH4 binding. Substitutions at five neighboring positions were tolerated, and
      normal binding of heme, calmodulin, and NADPH militated against major distortions
      affecting the NH2-terminal portion, midzone, or COOH terminus of the inactive
      mutants. Direct involvement of residues 450 and 453 in the binding of BH4 is
      supported by the striking homology of residues 448-480 to a region extensively
      shared by the three BH4-utilizing aromatic amino acid hydroxylases and is
      consistent with the conservation of these residues among all 10 reported NOS
      sequences, including mammalian NOSs 1, 2, and 3, as well as avian and insect
      NOSs. Altered binding of BH4 and/or L-arginine may explain how the addition of a
      single methyl group to the side chain of residue 450 or the addition of three
      methylenes to residue 453 can each abolish an enzymatic activity that reflects
      the concerted function of 1143 other residues.

PMID- 8524795
TI  - Proton transport by a bacteriorhodopsin mutant, aspartic acid-85-->asparagine,
      initiated in the unprotonated Schiff base state.
AB  - At alkaline pH the bacteriorhodopsin mutant D85N, with aspartic acid-85 replaced
      by asparagine, is in a yellow form (lambda max approximately 405 nm) with a
      deprotonated Schiff base. This state resembles the M intermediate of the wild
      type photocycle. We used time-resolved methods to show that this yellow form of
      D85N, which has an initially unprotonated Schiff base and which lacks the proton
      acceptor Asp-85, transports protons in the same direction as wild type when
      excited by 400-nm flashes. Photoexcitation leads in several milliseconds to the
      formation of blue (630 nm) and purple (580 nm) intermediates with a protonated
      Schiff base, which decay in tens of seconds to the initial state (400 nm).
      Experiments with pH indicator dyes show that at pH 7, 8, and 9, proton uptake
      occurs in about 5-10 ms and precedes the slow release (seconds). Photovoltage
      measurements reveal that the direction of proton movement is from the cytoplasmic
      to the extracellular side with major components on the millisecond and second
      time scales. The slowest electrical component could be observed in the presence
      of azide, which accelerates the return of the blue intermediate to the initial
      yellow state. Transport thus occurs in two steps. In the first step
      (milliseconds), the Schiff base is protonated by proton uptake from the
      cytoplasmic side, thereby forming the blue state. From the pH dependence of the
      amplitudes of the electrical and photocycle signals, we conclude that this
      reaction proceeds in a similar way as in wild type--i.e., via the internal proton
      donor Asp-96. In the second step (seconds) the Schiff base deprotonates,
      releasing the proton to the extracellular side.

PMID- 8524796
TI  - An amino acid sequence motif sufficient for subnuclear localization of an
      arginine/serine-rich splicing factor.
AB  - We have identified an amino acid sequence in the Drosophila Transformer (Tra)
      protein that is capable of directing a heterologous protein to nuclear speckles,
      regions of the nucleus previously shown to contain high concentrations of
      spliceosomal small nuclear RNAs and splicing factors. This sequence contains a
      nucleoplasmin-like bipartite nuclear localization signal (NLS) and a repeating
      arginine/serine (RS) dipeptide sequence adjacent to a short stretch of basic
      amino acids. Sequence comparisons from a number of other splicing factors that
      colocalize to nuclear speckles reveal the presence of one or more copies of this
      motif. We propose a two-step subnuclear localization mechanism for splicing
      factors. The first step is transport across the nuclear envelope via the
      nucleoplasmin-like NLS, while the second step is association with components in
      the speckled domain via the RS dipeptide sequence.

PMID- 8524797
TI  - Induction of a Cryphonectria parasitica cellobiohydrolase I gene is suppressed by
      hypovirus infection and regulated by a GTP-binding-protein-linked signaling
      pathway involved in fungal pathogenesis.
AB  - Extracellular cellulase activity is readily induced when the chestnut blight
      fungus Cryphonectria parasitica is grown on cellulose substrate as the sole
      carbon source. However, an isogenic C. parasitica strain rendered hypovirulent
      due to hypovirus infection failed to secrete detectable cellulase activity when
      grown under parallel conditions. Efforts to identify C. parasitica cellulase
      encoding genes resulted in the cloning of a cellobiohydrolase (exoglucanase, EC
      3.2.1.91) gene designated chb-1. Northern blot analysis revealed an increase in
      cbh-1 transcript accumulation in a virus-free virulent C. parasitica strain
      concomitant with the induction of extracellular cellulase activity. In contrast,
      induction of cbh-1 transcript accumulation was suppressed in an isogenic
      hypovirus-infected strain. Significantly, virus-free C. parasitica strains
      rendered hypovirulent by transgenic cosuppression of a GTP-binding protein alpha
      subunit were also found to be deficient in the induction of cbh-1 transcript
      accumulation.

PMID- 8524798
TI  - Regulation of microfilament organization and anchorage-independent growth by
      tropomyosin 1.
AB  - Variants of chemically immortalized Syrian hamster embryo cells that had either
      retained (supB+) or lost (supB-) the ability to suppress tumorigenicity when
      hybridized with a fibrosarcoma cell line were subcloned. Both supB cell types are
      nontumorigenic; however, the supB- but not supB+ cells exhibit conditional
      anchorage-independent growth. Alterations of actin microfilament organization
      were observed in supB- but not supB+ cells that corresponded to a significant
      reduction of the actin-binding protein tropomyosin 1 (TM-1) in subB- cells. To
      examine the possibility of a direct relationship between TM-1 expression and the
      subB- phenotype, subB+ cells were transfected with an expression vector
      containing the TM-1 cDNA in an antisense orientation. The antisense-induced
      reduction of TM-1 levels in supB+ clones caused a microfilament reorganization
      and conferred anchorage-independent growth potential that were indistinguishable
      from those characteristic of supB- cells. These data provide direct evidence that
      TM-1 regulates both microfilament organization and anchorage-independent growth
      and suggest that microfilament alterations are sufficient for anchorage
      independent growth.

PMID- 8524799
TI  - 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in
      Saccharomyces cerevisiae.
AB  - Deletion of the clathrin heavy-chain gene, CHC1, in the budding yeast
      Saccharomyces cerevisiae results in growth, morphological, and membrane
      trafficking defects, and in some strains chc1-delta is lethal. A previous study
      identified five genes which, in multicopy, rescue inviable strains of Chc- yeast.
      Now we report that one of the suppressor loci, BMH2/SCD3, encodes a protein of
      the 14-3-3 family. The 14-3-3 proteins are abundant acidic proteins of
      approximately 30 kDa with numerous isoforms and a diverse array of reported
      functions. The Bmh2 protein is > 70% identical to the mammalian epsilon-isoform
      and > 90% identical to a previously reported yeast 14-3-3 protein encoded by
      BMH1. Single deletions of BMH1 or BMH2 have no discernable phenotypes, but
      deletion of both BMH1 and BMH2 is lethal. High-copy BMH1 also rescues inviable
      strains of Chc- yeast, although not as well as BMH2. In addition, the slow growth
      of viable strains of Chc- yeast is further impaired when combined with single bmh
      mutations, often resulting in lethality. Overexpression of BMH genes also
      partially suppresses the temperature sensitivity of the cdc25-1 mutant, and high
      copy TPK1, encoding a cAMP-dependent protein kinase, restores Bmh- yeast to
      viability. High-copy TPK1 did not rescue Chc- yeast. These genetic interactions
      suggest that budding-yeast 14-3-3 proteins are multifunctional and may play a
      role in both vesicular transport and Ras signaling pathways.

PMID- 8524800
TI  - A potent transrepression domain in the retinoblastoma protein induces a cell
      cycle arrest when bound to E2F sites.
AB  - An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for
      the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F
      and for RB to induce a G1/S block. Indirect evidence suggests that the binding of
      RB to E2F may, in addition to inhibiting E2F transactivation function, generate a
      complex capable of functioning as a transrepressor. Here we show that a chimera
      in which the E2F1 transactivation domain was replaced with the RB pocket could,
      in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress
      transcription and induce a cell cycle arrest. In contrast, a transdominant
      negative E2F1 mutant that is capable of blocking E2F-dependent transactivation
      did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated
      to E2F likewise generated a transrepressor protein when scored against a suitable
      reporter. These results suggest that growth suppression by RB is due, at least in
      part, to transrepression mediated by the pocket domain bound to certain promoters
      via E2F.

PMID- 8524801
TI  - Microsatellite variability and genetic distances.
AB  - We analyze the within- and between-population dynamics of the distribution of the
      number of repeats at multiple microsatellite DNA loci subject to stepwise
      mutation. Analytical expressions for moments up to the fourth order within a
      locus and the variance of between-locus variance at mutation-drift equilibrium
      have been obtained. These statistics may be used to test the appropriateness of
      the one-step mutation model and to detect between-locus variation in the mutation
      rate. Published data are compatible with the one-step mutation model, although
      they do not reject the two-step model. Using both multinomial sampling and
      diffusion approximations for the analysis of the genetic distance introduced by
      Goldstein et al. [Goldstein, D. B., Linares, A. R., Cavalli-Sforza, L. L. &
      Feldman, M. W. (1995) Proc. Natl. Acad. Sci. USA 92, 6723-6727], we show that
      this distance follows a chi 2 distribution with degrees of freedom equal to the
      number of loci when there is no variation in mutation rates among the loci. In
      the presence of such variation, the variance of the distance is obtained. We
      conclude that the number of microsatellite loci required for the construction of
      phylogenetic trees with reliable branch lengths may be several hundred. Also,
      mutations that change repeat scores by several units, even though extremely rare,
      may dramatically influence estimates of population parameters.

PMID- 8524802
TI  - Systemic immunization with papillomavirus L1 protein completely prevents the
      development of viral mucosal papillomas.
AB  - Infection of mucosal epithelium by papillomaviruses is responsible for the
      induction of genital and oral warts and plays a critical role in the development
      of human cervical and oropharyngeal cancer. We have employed a canine model to
      develop a systemic vaccine that completely protects against experimentally
      induced oral mucosal papillomas. The major capsid protein, L1, of canine oral
      papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation.
      L1 protein, which self-assembled into virus-like particles, was purified on CsCl
      gradients and injected intradermally into the foot pad of beagles. Vaccinated
      animals developed circulating antibodies against COPV and became completely
      resistant to experimental challenge with COPV. Successful immunization was
      strictly dependent upon native L1 protein conformation and L1 type. Partial
      protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants
      appeared useful for prolonging the host immune response. Serum immunoglobulins
      passively transferred from COPV L1-immunized beagles to naive beagles conferred
      protection from experimental infection with COPV. Our results indicate the
      feasibility of developing a human vaccine to prevent mucosal papillomas, which
      can progress to malignancy.

PMID- 8524803
TI  - The CD19 signal transduction molecule is a response regulator of B-lymphocyte
      differentiation.
AB  - The phenotypes of CD19-deficient (CD19-/-) mice, and human CD19-transgenic
      (hCD19TG) mice that overexpress CD19 indicate that CD19 is a response regulator
      of B-lymphocyte surface receptor signaling. To further characterize the function
      of CD19 during B-cell differentiation, humoral immune responses to a T-cell
      independent type 1 [trinitrophenyl-lipopolysaccharide (TNP-LPS)], a T-cell
      independent type 2 [dinitrophenyl (DNP)-Ficoll], and a T-cell-dependent [DNP
      keyhole limpet hemocyanin (KLH)] antigen were assessed in CD19-/- and hCD19TG
      mice. B cells from CD19-/- mice differentiated and underwent immunoglobulin
      isotype switching in vitro in response to mitogens and cytokines. In vivo, CD19-/
      mice generated humoral responses to TNP-LPS and DNP-KLH that were dramatically
      lower than those of wild-type littermates. Surprisingly, the humoral response to
      DNP-Ficoll was significantly greater in CD19-/- mice. In contrast, hCD19TG mice
      were hyperresponsive to TNP-LPS and DNP-KLH immunization but were hyporesponsive
      to DNP-Ficoll. These results demonstrate that CD19 is not required for B-cell
      differentiation and isotype switching but serves as a response regulator which
      modulates B-cell differentiation. Since humoral responses to both T-cell
      dependent and T-cell-independent antigens were similarly affected by alterations
      in CD19 expression, these differences are most likely to result from intrinsic
      changes in B-cell function rather than from the selective disruption of B-cell
      interactions with T cells.

PMID- 8524804
TI  - Production of infectious human respiratory syncytial virus from cloned cDNA
      confirms an essential role for the transcription elongation factor from the 5'
      proximal open reading frame of the M2 mRNA in gene expression and provides a
      capability for vaccine development.
AB  - Infectious human respiratory syncytial virus (RSV) was produced by the
      intracellular coexpression of five plasmid-borne cDNAs. One cDNA encoded a
      complete positive-sense version of the RSV genome (corresponding to the
      replicative intermediate RNA or antigenome), and each of the other four encoded a
      separate RSV protein, namely, the major nucleocapsid N protein, the nucleocapsid
      P phosphoprotein, the major polymerase L protein, or the protein from the 5'
      proximal open reading frame of the M2 mRNA [M2(ORF1)]. RSV was not produced if
      any of the five plasmids was omitted. The requirement for the M2(ORF1) protein is
      consistent with its recent identification as a transcription elongation factor
      and confirms its importance for RSV gene expression. It should thus be possible
      to introduce defined changes into infectious RSV. This should be useful for basic
      studies of RSV molecular biology and pathogenesis; in addition, there are
      immediate applications to the development of live attenuated vaccine strains
      bearing predetermined defined attenuating mutations.

PMID- 8524805
TI  - Temporal fluctuations in coherence of brain waves.
AB  - As a measure of dynamical structure, short-term fluctuations of coherence between
      0.3 and 100 Hz in the electroencephalogram (EEG) of humans were studied from
      recordings made by chronic subdural macroelectrodes 5-10 mm apart, on temporal,
      frontal, and parietal lobes, and from intracranial probes deep in the temporal
      lobe, including the hippocampus, during sleep, alert, and seizure states. The
      time series of coherence between adjacent sites calculated every second or less
      often varies widely in stability over time; sometimes it is stable for half a
      minute or more. Within 2-min samples, coherence commonly fluctuates by a factor
      up to 2-3, in all bands, within the time scale of seconds to tens of seconds. The
      power spectrum of the time series of these fluctuations is broad, extending to
      0.02 Hz or slower, and is weighted toward the slower frequencies; little power is
      faster than 0.5 Hz. Some records show conspicuous swings with a preferred
      duration of 5-15s, either irregularly or quasirhythmically with a broad peak
      around 0.1 Hz. Periodicity is not statistically significant in most records. In
      our sampling, we have not found a consistent difference between lobes of the
      brain, subdural and depth electrodes, or sleeping and waking states. Seizures
      generally raise the mean coherence in all frequencies and may reduce the
      fluctuations by a ceiling effect. The coherence time series of different bands is
      positively correlated (0.45 overall); significant nonindependence extends for at
      least two octaves. Coherence fluctuations are quite local; the time series of
      adjacent electrodes is correlated with that of the nearest neighbor pairs (10 mm)
      to a coefficient averaging approximately 0.4, falling to approximately 0.2 for
      neighbors-but-one (20 mm) and to < 0.1 for neighbors-but-two (30 mm). The
      evidence indicates fine structure in time and space, a dynamic and local
      determination of this measure of cooperativity. Widely separated frequencies
      tending to fluctuate together exclude independent oscillators as the general or
      usual basis of the EEG, although a few rhythms are well known under special
      conditions. Broad-band events may be the more usual generators. Loci only a few
      millimeters apart can fluctuate widely in seconds, either in parallel or
      independently. Scalp EEG coherence cannot be predicted from subdural or deep
      recordings, or vice versa, and intracortical microelectrodes show still greater
      coherence fluctuation in space and time. Widely used computations of chaos and
      dimensionality made upon data from scalp or even subdural or depth electrodes,
      even when reproducible in successive samples, cannot be considered representative
      of the brain or the given structure or brain state but only of the scale or view
      (receptive field) of the electrodes used. Relevant to the evolution of more
      complex brains, which is an outstanding fact of animal evolution, we believe that
      measures of cooperativity are likely to be among the dynamic features by which
      major evolutionary grades of brains differ.

PMID- 8524806
TI  - An apical permeability barrier to NH3/NH4+ in isolated, perfused colonic crypts.
AB  - Fermentation of nonabsorbed nutrients in the colon generates high concentrations
      of NH3/NH4+ in the colonic lumen. NH3 is a small, lipophilic neutral weak base
      that readily permeates almost all cell membranes, whereas its conjugate weak acid
      NH4+ generally crosses membranes much more slowly. It is not known how
      colonocytes maintain intracellular pH in the unusual acid-base environment of the
      colon, where permeant acid-base products of fermentation exist in high
      concentration. To address this issue, we hand dissected and perfused single,
      isolated crypts from rabbit proximal colon, adapting techniques from renal-tubule
      microperfusion. Crypt perfusion permits control of solutions at the apical
      (luminal) and basolateral (serosal) surfaces of crypt cells. We assessed apical-
      vs. basolateral-membrane transport of NH3/NH4+ by using fluorescent dyes and
      digital imaging to monitor intracellular pH of microvacuolated crypt cells as
      well as luminal pH. We found that, although the basolateral membranes have normal
      NH3/NH4+ permeability properties, there is no evidence for transport of either
      NH3 or NH4+ across the apical borders of these crypt cells. Disaggregating
      luminal mucus did not increase the transport of NH3/NH4+ across the apical
      border. We conclude that, compared to the basolateral membrane, the apical border
      of crypt colonocytes has a very low permeability-area product for NH3/NH4+. This
      barrier may represent an important adaptation for the survival of crypt cells in
      the environment of the colon.

PMID- 8524807
TI  - Projection structure of frog rhodopsin in two crystal forms.
AB  - Rhodopsin is the G protein-coupled receptor that upon light activation triggers
      the visual transduction cascade. Rod cell outer segment disc membranes were
      isolated from dark-adapted frog retinas and were extracted with Tween detergents
      to obtain two-dimensional rhodopsin crystals for electron crystallography. When
      Tween 80 was used, tubular structures with a p2 lattice (a = 32 A, b = 83 A,
      gamma = 91 degrees) were formed. The use of a Tween 80/Tween 20 mixture favored
      the formation of larger p22(1)2(1) lattices (a = 40 A, b = 146 A, gamma = 90
      degrees). Micrographs from frozen hydrated frog rhodopsin crystals were
      processed, and projection structures to 7-A resolution for the p22(1)2(1) form
      and to 6-A resolution for the p2 form were calculated. The maps of frog rhodopsin
      in both crystal forms are very similar to the 9-A map obtained previously for
      bovine rhodopsin and show that the arrangement of the helices is the same. In a
      tentative topographic model, helices 4, 6, and 7 are nearly perpendicular to the
      plane of the membrane. In the higher-resolution projection maps of frog
      rhodopsin, helix 5 looks more tilted than it appeared previously. The quality of
      the two frog rhodopsin crystals suggests that they would be suitable to obtain a
      three-dimensional structure in which all helices would be resolved.

PMID- 8524808
TI  - Coupling the phosphotransferase system and the methyl-accepting chemotaxis
      protein-dependent chemotaxis signaling pathways of Escherichia coli.
AB  - Chemotactic responses in Escherichia coli are typically mediated by transmembrane
      receptors that monitor chemoeffector levels with periplasmic binding domains and
      communicate with the flagellar motors through two cytoplasmic proteins, CheA and
      CheY. CheA autophosphorylates and then donates its phosphate to CheY, which in
      turn controls flagellar rotation. E. coli also exhibits chemotactic responses to
      substrates that are transported by the phosphoenolpyruvate (PEP)-dependent
      carbohydrate phosphotransferase system (PTS). Unlike conventional chemoreception,
      PTS substrates are sensed during their uptake and concomitant phosphorylation by
      the cell. The phosphoryl groups are transferred from PEP to the carbohydrates
      through two common intermediates, enzyme I (EI) and phosphohistidine carrier
      protein (HPr), and then to sugar-specific enzymes II. We found that in mutant
      strains HPr-like proteins could substitute for HPr in transport but did not
      mediate chemotactic signaling. In in vitro assays, these proteins exhibited
      reduced phosphotransfer rates from EI, indicating that the phosphorylation state
      of EI might link the PTS phospho-relay to the flagellar signaling pathway. Tests
      with purified proteins revealed that unphosphorylated EI inhibited CheA
      autophosphorylation, whereas phosphorylated EI did not. These findings suggest
      the following model for signal transduction in PTS-dependent chemotaxis. During
      uptake of a PTS carbohydrate, EI is dephosphorylated more rapidly by HPr than it
      is phosphorylated at the expense of PEP. Consequently, unphosphorylated EI builds
      up and inhibits CheA autophosphorylation. This slows the flow of phosphates to
      CheY, eliciting an up-gradient swimming response by the cell.

PMID- 8524809
TI  - Escherichia coli transcript cleavage factors GreA and GreB stimulate promoter
      escape and gene expression in vivo and in vitro.
AB  - The process of RNA chain initiation by RNA polymerases plays a central role in
      the regulation of transcription. In this complex phase of transcription, short
      oligomers are synthesized and released from the enzyme-promoter complex in a
      reaction termed abortive initiation. The polymerase undergoes many cycles of
      abortive initiation prior to completion of the initiation process, which is
      signaled by the translocation of the enzyme away from the promoter, release of
      sigma factor, and formation of an elongation complex in which the RNA is stably
      bound. We have studied the parameters that affect escape from the promoter by
      Escherichia coli RNA polymerase for the phage T7 A1 promoter, the phage T5 N25
      promoter, and the chimeric promoter T5 N25antiDSR. The latter site contains a
      synthetic initial transcribed region that reduces its ability to synthesize RNA
      both in vivo and in vitro. Clearance from T5 N25antiDSR can be stimulated up to
      10-fold in vitro by addition of the E. coli transcript cleavage factor GreA or
      GreB, but these factors have little effect on transcription from the normal T7 A1
      or T5 N25 promoters. Using an E. coli strain lacking GreA and GreB, we were also
      able to show stimulation of transcription by the Gre factors from the T5
      N25antiDSR promotor in vivo. The stimulation of RNA chain initiation by Gre
      factors, together with their known biochemical properties in the transcription
      elongation reaction, suggests some specific models for steps in the transcription
      initiation reaction.

PMID- 8524811
TI  - Alternative translation initiation site usage results in two functionally
      distinct forms of the GATA-1 transcription factor.
AB  - GATA-1 is a zinc-finger transcription factor that plays a critical role in the
      normal development of hematopoietic cell lineages. In human and murine erythroid
      cells a previously undescribed 40-kDa protein is detected with GATA-1-specific
      antibodies. We show that the 40-kDa GATA-1 (GATA-1s) is produced by the use of an
      internal AUG initiation codon in the GATA-1 transcript. The GATA-1 proteins share
      identical binding activity and form heterodimers in erythroleukemic cells but
      differ in their transactivation potential and in their expression in developing
      mouse embryos.

PMID- 8524810
TI  - Thyroid hormone (T3) inhibits ciprofibrate-induced transcription of genes
      encoding beta-oxidation enzymes: cross talk between peroxisome proliferator and
      T3 signaling pathways.
AB  - Peroxisome proliferators cause rapid and coordinated transcriptional activation
      of genes encoding peroxisomal beta-oxidation system enzymes by activating
      peroxisome proliferator-activated receptor (PPAR) isoform(s). Since the thyroid
      hormone (T3; 3,3',5-triiodothyronine) receptor (TR), another member of the
      nuclear hormone receptor superfamily, regulates a subset of fatty acid metabolism
      genes shared with PPAR, we examined the possibility of interplay between
      peroxisome proliferator and T3 signaling pathways. T3 inhibited ciprofibrate
      induced luciferase activity as well as the endogenous peroxisomal beta-oxidation
      enzymes in transgenic mice carrying a 3.2-kb 5'-flanking region of the rat
      peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase gene fused to the
      coding region of luciferase. Transfection assays in hepatoma H4-II-E-C3 and CV-1
      cells indicated that this inhibition is mediated by TR in a ligand-dependent
      fashion. Gel shift assays revealed that modulation of PPAR action by TR occurs
      through titration of limiting amounts of retinoid X receptor (RXR) required for
      PPAR activation. Increasing amounts of RXR partially reversed the inhibition in a
      reciprocal manner; PPAR also inhibited TR activation. Results with
      heterodimerization-deficient TR and PPAR mutants further confirmed that
      interaction between PPAR and TR signaling systems is indirect. These results
      suggest that a convergence of the peroxisome proliferator and T3 signaling
      pathways occurs through their common interaction with the heterodimeric partner
      RXR.

PMID- 8524812
TI  - Phosphinate analogs of D-, D-dipeptides: slow-binding inhibition and proteolysis
      protection of VanX, a D-, D-dipeptidase required for vancomycin resistance in
      Enterococcus faecium.
AB  - VanX is a D-Ala-D-Ala dipeptidase that is essential for vancomycin resistance in
      Enterococcus faecium. Contrary to most proteases and peptidases, it prefers to
      hydrolyze the amino substrate but not the related kinetically and
      thermodynamically more favorable ester substrate D-Ala-D-lactate. The enzymatic
      activity of VanX was previously found to be inhibited by the phosphinate analogs
      of the proposed tetrahedral intermediate for hydrolysis of D-Ala-D-Ala. Here we
      report that such phosphinates are slow-binding inhibitors. D-3-[(1
      Aminoethyl)phosphinyl]-D-2-methylpropionic acid I showed a time-dependent onset
      of inhibition of VanX and a time-dependent return to uninhibited steady-state
      rates upon dilution of the enzyme/inhibitor mixture. The initial inhibition
      constant Ki after immediate addition of VanX to phosphinate I to form the E-I
      complex is 1.5 microM but is then lowered by a relatively slow isomerization step
      to a second complex, E-I*, with a final K*i of 0.47 microM. This slow-binding
      inhibition reflects a Km/K*i ratio of 2900:1. The rate constant for the slow
      dissociation of complex E-I* is 0.24 min-1. A phosphinate analog with an ethyl
      group replacing what would be the side chain of the second D-alanyl residue in
      the normal tetrahedral adduct gives a K*i value of 90 nM. Partial proteolysis of
      VanX reveals two protease-sensitive loop regions that are protected by the
      intermediate analog phosphinate, indicating that they may be part of the VanX
      active site.

PMID- 8524813
TI  - A mouse model for beta 0-thalassemia.
AB  - We have used a "plug and socket" targeting technique to generate a mouse model of
      beta 0-thalassemia in which both the b1 and b2 adult globin genes have been
      deleted. Mice homozygous for this deletion (Hbbth-3/Hbbth-3) die perinatally,
      similar to the most severe form of Cooley anemia in humans. Mice heterozygous for
      the deletion appear normal, but their hematologic indices show characteristics
      typical of severe thalassemia, including dramatically decreased hematocrit,
      hemoglobin, red blood cell counts, mean corpuscular volume, mean corpuscular
      hemoglobin, and mean corpuscular hemoglobin concentration, as well as
      dramatically increased reticulocyte counts, serum bilirubin concentrations, and
      red cell distribution widths. Tissue and organ damage typical of beta
      thalassemia, such as bone deformities and splenic enlargement due to increased
      hematopoiesis, are also seen in the heterozygous animals, as is spontaneous iron
      overload in the spleen, liver, and kidneys. The mice homozygous for the b1 and b2
      deletions should be of great value in developing therapies for the treatment of
      thalassemias in utero. The heterozygous animals will be useful for studying the
      pathophysiology of thalassemias and have the potential of generating a model of
      sickle cell anemia when mated with appropriate transgenic animals.

PMID- 8524814
TI  - Phosphatidylinositol 3-kinase binding to polyoma virus middle tumor antigen
      mediates elevation of glucose transport by increasing translocation of the GLUT1
      transporter.
AB  - Elevation in the rate of glucose transport in polyoma virus-infected mouse
      fibroblasts was dependent upon phosphatidylinositol 3-kinase (PI 3-kinase; EC
      2.7.1.137) binding to complexes of middle tumor antigen (middle T) and pp60c-src.
      Wild-type polyoma virus infection led to a 3-fold increase in the rate of 2
      deoxyglucose (2DG) uptake, whereas a weakly transforming polyoma virus mutant
      that encodes a middle T capable of activating pp60c-src but unable to promote
      binding of PI 3-kinase induced little or no change in the rate of 2DG transport.
      Another transformation-defective mutant encoding a middle T that retains
      functional binding of both pp60c-src and PI 3-kinase but is incapable of binding
      Shc (a protein involved in activation of Ras) induced 2DG transport to wild-type
      levels. Wortmannin (< or = 100 nM), a known inhibitor of PI 3-kinase, blocked
      elevation of glucose transport in wild-type virus-infected cells. In contrast to
      serum stimulation, which led to increased levels of glucose transporter 1 (GLUT1)
      RNA and protein, wild-type virus infection induced no significant change in
      levels of either GLUT1 RNA or protein. Nevertheless, virus-infected cells did
      show increases in GLUT1 protein in plasma membranes. These results point to a
      posttranslational mechanism in the elevation of glucose transport by polyoma
      virus middle T involving activation of PI 3-kinase and translocation of GLUT1.

PMID- 8524815
TI  - Cloning and characterization of Lnk, a signal transduction protein that links T
      cell receptor activation signal to phospholipase C gamma 1, Grb2, and
      phosphatidylinositol 3-kinase.
AB  - A cDNA encoding a signal transduction protein with a Src homology 2 (SH2) domain
      and a tyrosine phosphorylation site was cloned from a rat lymph node cDNA
      library. This protein, which we designate Lnk, has a calculated molecular weight
      of 33,988. When T lymphocytes were activated by antibody-mediated crosslinking of
      the T-cell receptor and CD4, Lnk became tyrosine phosphorylated. In activated T
      lymphocytes, phospholipase C gamma 1, phosphatidylinositol 3-kinase, and Grb-2
      coimmunoprecipitated with Lnk. Our results suggest that Lnk becomes tyrosine
      phosphorylated and links the immediate tyrosine phosphorylation signals of the
      TCR to the distal phosphatidylinositol 3-kinase, phospholipase C gamma 1 and Ras
      signaling pathways through its multifunctional tyrosine phosphorylation site.

PMID- 8524816
TI  - Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for
      differential gene expression in T helper cell subsets.
AB  - Activation of individual CD4+ T cells results in differential lymphokine
      expression: interleukin 2 (IL-2) is preferentially produced by T helper type 1
      (TH1) cells, which are involved in cell-mediated immune responses, whereas IL-4
      is synthesized by TH2 cells, which are essential for humoral immunity. The Ca(2+)
      dependent factor NF-ATp plays a key role in the inducible transcription of both
      these lymphokine genes. However, while IL2 expression requires the contribution
      of Ca(2+)- and protein kinase C-dependent signals, we report that activation of
      human IL4 transcription through the Ca(2+)-dependent pathway is diminished by
      protein kinase C stimulation in Jurkat T cells. This phenomenon is due to
      mutually exclusive binding of NF-ATp and NF-kappa B to the P sequence, an element
      located 69 bp upstream of the IL4 transcription initiation site. Human IL4
      promoter-mediated transcription is downregulated in Jurkat cells stimulated with
      the NF-kappa B-activating cytokine tumor necrosis factor alpha and suppressed in
      RelA-overexpressing cells. In contrast, protein kinase C stimulation or RelA
      overexpression does not affect the activity of a human IL4 promoter containing a
      mouse P sequence, which is a higher-affinity site for NF-ATp and a lower-affinity
      site for RelA. Thus, competition between two general transcriptional activators,
      RelA and NF-ATp, mediates the inhibitory effect of protein kinase C stimulation
      on IL4 expression and may contribute to differential gene expression in TH cells.

PMID- 8524817
TI  - FAS is highly expressed in the germinal center but is not required for regulation
      of the B-cell response to antigen.
AB  - In establishing the memory B-cell population and maintaining self-tolerance
      during an immune response, apoptosis mediates the removal of early, low-affinity
      antibody-forming cells, unselected germinal center (GC) cells, and, potentially,
      self-reactive B cells. To address the role of the apoptosis-signaling cell
      surface molecule FAS in the B-cell response to antigen, we have examined the T
      cell-dependent B-cell response to the carrier-conjugated hapten (4-hydroxy-3
      nitrophenyl)acetyl (NP) in lpr mice in which the fas gene is mutated. High levels
      of FAS were expressed on normal GC B cells but the absence of FAS did not perturb
      the progressive decline in numbers of either GC B cells or extrafollicular
      antibody-forming cells. Furthermore, the rate of formation and eventual size of
      the NP-specific memory B-cell population in lpr mice were normal. The
      accumulation of cells with affinity-enhancing mutations and the appearance of
      high-affinity anti-NP IgG1 antibody in the serum were also normal in lpr mice.
      Thus, although high levels of FAS are expressed on GC B cells, FAS is not
      required for GC selection or for regulation of the major antigen-specific B-cell
      compartments. The results suggest that the size and composition of B-cell
      compartments in the humoral immune response are regulated by mechanisms that do
      not require FAS.

PMID- 8524818
TI  - Characterization of a 23-kDa protein associated with CD40.
AB  - CD40 is a 45-kDa glycoprotein member of the tumor necrosis factor receptor (TNFR)
      family expressed on B cells, thymic epithelial cells, dendritic cells, and some
      carcinoma cells. The unique capacity of CD40 to trigger immunoglobulin isotype
      switching is dependent on the activation of protein-tyrosine kinases, yet CD40
      possesses no kinase domain and no known consensus sequences for binding to
      protein-tyrosine kinases. Recently, an intracellular protein (CD40bp/LAP-1/CRAF
      1) which belongs to the family of TNFR-associated proteins was reported to
      associate with CD40. We describe a 23-kDa cell surface protein (p23) which is
      specifically associated with CD40 on B cells and on urinary bladder transitional
      carcinoma cells. Protein microsequencing revealed that p23 shows no homology to
      any known protein. A rabbit antibody raised against a peptide derived from p23
      recognized a 23-kDa protein in CD40 immunoprecipitates. In contrast to CD40bp/LAP
      1/CRAF-1, p23 was not associated with TNFR p80 (CD120b). These findings suggest
      that p23 is a novel member of the CD40 receptor complex.

PMID- 8524819
TI  - Cooperative interactions among afferents govern the induction of homosynaptic
      long-term depression in the hippocampus.
AB  - Prolonged periods of low-frequency stimulation have been shown to produce a
      robust, long-term synaptic depression (LTD) in both hippocampus and visual
      cortex. In the present study we have examined the extent to which interactions
      among afferents govern the induction of homosynaptic LTD in young-adult rats in
      hippocampal region CA1 in vitro. Field excitatory postsynaptic potentials were
      assessed before and after conditioning stimulation consisting of two 10-min
      trains of low-frequency stimulation (LFS; 1 Hz) of the Schaffer
      collateral/commissural pathway. LFS at an intensity producing a 0.5-mV response
      did not produce significant synaptic depression. However, LFS administered at a
      higher intensity resulted in significant input-specific LTD of a 0.5-mV test
      response. Picrotoxin, which also facilitates depolarization of CA1 neurons,
      significantly enhanced the magnitude of LTD after LFS at 0.5 mV. In addition, LFS
      at 0.5 mV in normal perfusion medium (no picrotoxin) produced only small changes
      in synaptic efficacy when either of two converging pathways was conditioned
      separately but produced a robust LTD when both pathways were conditioned
      simultaneously. This cooperative LTD was reversibly blocked by prior
      administration of 100 microM DL-aminophosphonovaleric acid but not by 20 microM
      nimodipine. Taken together, these results suggest that cooperative interactions
      among afferents contribute to voltage-dependent processes underlying the
      induction of homosynaptic LTD.

PMID- 8524820
TI  - Identification of a receptor/G-protein contact site critical for signaling
      specificity and G-protein activation.
AB  - Each G protein-coupled receptor recognizes only a distinct subset of the many
      structurally closely related G proteins expressed within a cell. How this
      selectively is achieved at a molecular level is not well understood, particularly
      since no specific point-to-point contact sites between a receptor and its cognate
      G protein(s) have been identified. In this study, we demonstrate that a 4-aa
      epitope on the m2 muscarinic acetylcholine receptor, a prototypical Gi/o-coupled
      receptor, can specifically recognize the C-terminal 5 aa of alpha subunits of the
      Gi/o protein family. The m2 receptor residues involved in this interaction are
      predicted to be located on one side of an alpha-helical receptor region present
      at the junction between the third intracellular loop and the sixth transmembrane
      domain. Coexpression studies with hybrid m2/m3 muscarinic receptors and mutant G
      protein alpha q subunits showed that the receptor/G-protein contact site
      identified in this study is essential for coupling specificity and G-protein
      activation.

PMID- 8524821
TI  - Molecular cloning of a preprohormone from sea anemones containing numerous copies
      of a metamorphosis-inducing neuropeptide: a likely role for dipeptidyl
      aminopeptidase in neuropeptide precursor processing.
AB  - Neuropeptides are an important group of hormones mediating or modulating neuronal
      communication. Neuropeptides are especially abundant in evolutionarily "old"
      nervous systems, such as those of cnidarians, the lowest animal group having a
      nervous system. Cnidarians often have a life cycle including a polyp, a medusa,
      and a planula larva stage. Recently, a neuropeptide, < Glu-Gln-Pro-Gly-Leu-Trp
      NH2, has been isolated from sea anemones that induces metamorphosis in a hydroid
      planula larva to become a hydropolyp [Leitz, T., Morand, K. & Mann, M. (1994)
      Dev. Biol. 163, 440-446]. Here, we have cloned the precursor protein for this
      metamorphosis-inducing neuropeptide from sea anemones. The precursor protein is
      514-amino acid residues long and contains 10 copies of the immature, authentic
      neuropeptide (Gln-Gln-Pro-Gly-Leu-Trp-Gly). All neuropeptide copies are preceded
      by Xaa-Pro or Xaa-Ala sequences, suggesting a role for dipeptidyl aminopeptidase
      in neuropeptide precursor processing. In addition to these neuropeptide copies,
      there are 14 copies of another, closely related neuropeptide sequence (Gln-Asn
      Pro-Gly-Leu-Trp-Gly). These copies are flanked by basic cleavage sites and,
      therefore, are likely to be released from the precursor protein. Furthermore,
      there are 13 other, related neuropeptide sequences having only small sequence
      variations (the most frequent sequence: Gln-Pro-Gly-Leu-Trp-Gly, eight copies).
      These variants are preceded by Lys-Arg, Xaa-Ala, or Xaa-Pro sequences, and are
      followed by basic cleavage sites, and therefore, are also likely to be produced
      from the precursor. Thus, there are at least 37 closely related neuropeptides
      localized on the precursor protein, making this precursor one of the most
      productive preprohormones known so far. This report also shows that unusual
      processing sites are common in cnidarian preprohormones.

PMID- 8524822
TI  - Purification, cloning, and functional expression of sucrose:fructan 6
      fructosyltransferase, a key enzyme of fructan synthesis in barley.
AB  - Fructans play an important role in assimilate partitioning and possibly in stress
      tolerance in many plant families. Sucrose:fructan 6-fructosyltransferase (6-SFT),
      an enzyme catalyzing the formation and extension of beta-2,6-linked fructans
      typical of grasses, was purified from barley (Hordeum vulgare L.). It occurred in
      two closely similar isoforms with indistinguishable catalytic properties, both
      consisting of two subunits with apparent masses of 49 and 23 kDa.
      Oligonucleotides, designed according to the sequences of tryptic peptides from
      the large subunit, were used to amplify corresponding sequences from barley cDNA.
      The main fragment generated was cloned and used to screen a barley cDNA
      expression library. The longest cDNA obtained was transiently expressed in
      Nicotiana plumbaginifolia protoplasts and shown to encode a functional 6-SFT. The
      deduced amino acid sequence of the cDNA comprises both subunits of 6-SFT. It has
      high similarity to plant invertases and other beta-fructosyl hydrolases but only
      little to bacterial fructosyltransferases catalyzing the same type of reaction as
      6-SFT.

PMID- 8524823
TI  - Identification of a member of the interferon regulatory factor family that binds
      to the interferon-stimulated response element and activates expression of
      interferon-induced genes.
AB  - A family of interferon (IFN) regulatory factors (IRFs) have been shown to play a
      role in transcription of IFN genes as well as IFN-stimulated genes. We report the
      identification of a member of the IRF family which we have named IRF-3. The IRF-3
      gene is present in a single copy in human genomic DNA. It is expressed
      constitutively in a variety of tissues and no increase in the relative steady
      state levels of IRF-3 mRNA was observed in virus-infected or IFN-treated cells.
      The IRF-3 gene encodes a 50-kDa protein that binds specifically to the IFN
      stimulated response element (ISRE) but not to the IRF-1 binding site PRD-I.
      Overexpression of IRF-3 stimulates expression of the IFN-stimulated gene 15
      (ISG15) promoter, an ISRE-containing promoter. The murine IFNA4 promoter, which
      can be induced by IRF-1 or viral infection, is not induced by IRF-3. Expression
      of IRF-3 as a Gal4 fusion protein does not activate expression of a
      chloramphenicol acetyltransferase reporter gene containing repeats of the Gal4
      binding sites, indicating that this protein does not contain the transcription
      transactivation domain. The high amino acid homology between IRF-3 and ISG factor
      3 gamma polypeptide (ISGF3 gamma) and their similar binding properties indicate
      that, like ISGF3 gamma, IRF-3 may activate transcription by complex formation
      with other transcriptional factors, possibly members of the Stat family.
      Identification of this ISRE-binding protein may help us to understand the
      specificity in the various Stat pathways.

PMID- 8524824
TI  - Phylogenetic relationships of the hoatzin, an enigmatic South American bird.
AB  - The hoatzin (Opisthocomus hoazin) lives in the humid lowlands of northern and
      central South America, often in riparian habitats. It is a slender bird
      approximately 65 cm in length, brownish with lighter streaks and buffy tips to
      the long tail feathers. The small head has a ragged, bristly crest of reddish
      brown feathers, and the bare skin of the face is bright blue. It resembles a
      chachalaca (Ortalis, Cracidae) in size and shape, but its plumage and markings
      are similar to those of the smaller guira cuckoo (Guira guira). The hoatzin
      (pronounced Watson) has been a taxonomic puzzle since it was described in 1776.
      It usually has been viewed as related to the gallinaceous birds, but alliances to
      other groups have been suggested, including the cuckoos. We present DNA sequence
      evidence from the 12S and 16S rRNA mitochondrial genes, and from the nuclear gene
      that codes for the eye lens protein, alpha A-crystallin. The results indicate
      that the hoatzin is most closely related to the typical cuckoos and that the
      divergence occurred at or near the base of the cuculiform phylogenetic tree.

PMID- 8524825
TI  - A highly active decarboxylating dehydrogenase with rationally inverted coenzyme
      specificity.
AB  - The isocitrate dehydrogenase of Escherichia coli, which lacks the Rossmann fold
      common to other dehydrogenases, displays a 7000-fold preference for NADP over NAD
      (calculated as the ratio of kcat/Km). Guided by x-ray crystal structures and
      molecular modeling, site-directed mutagenesis has been used to introduce six
      substitutions in the adenosine binding pocket that systematically shift coenzyme
      preference toward NAD. The engineered enzyme displays an 850-fold preference for
      NAD over NADP, which exceeds the 140-fold preference displayed by a homologous
      NAD-dependent enzyme. Of the six mutations introduced, only one is identical in
      all related NAD-dependent enzyme sequences--strict adherence to homology as a
      criterion for replacing these amino acids impairs function. Two additional
      mutations at remote sites improve performance further, resulting in a final
      mutant enzyme with kinetic characteristics and coenzyme preference comparable to
      naturally occurring homologous NAD-dependent enzymes.

PMID- 8524826
TI  - Engineering an intracellular pathway for major histocompatibility complex class
      II presentation of antigens.
AB  - The presentation of antigenic peptides by major histocompatibility complex (MHC)
      class II molecules to CD4+ T cells is critical to the function of the immune
      system. In this study, we have utilized the sorting signal of the lysosomal
      associated membrane protein LAMP-1 to target a model antigen, human
      papillomavirus 16 E7 (HPV-16 E7), into the endosomal and lysosomal compartments.
      The LAMP-1 sorting signal reroutes the antigen into the MHC class II processing
      pathway, resulting in enhanced presentation to CD4+ cells in vitro. In vivo
      immunization experiments in mice demonstrated that vaccinia containing the
      chimeric E7/LAMP-1 gene generated greater E7-specific lymphoproliferative
      activity, antibody titers, and cytotoxic T-lymphocyte activities than vaccinia
      containing the wild-type HPV-16 E7 gene. These results suggest that specific
      targeting of an antigen to the endosomal and lysosomal compartments enhances MHC
      class II presentation and vaccine potency.

PMID- 8524827
TI  - Molecular heterogeneity of progenitors and radial migration in the developing
      cerebral cortex revealed by transgene expression.
AB  - We have analyzed the developmental pattern of beta-galactosidase (beta-gal)
      expression in the cerebral cortex of the beta 2nZ3'1 transgenic mouse line, which
      was generated using regulatory elements of the beta 2-microglobulin gene and
      shows ectopic expression in nervous tissue. From embryonic day 10 onward, beta
      gal was expressed in the medial and dorsal cortices, including the hippocampal
      region, whereas lateral cortical areas were devoid of labeling. During the period
      of cortical neurogenesis (embryonic days 11-17), beta-gal was expressed by
      selective precursors in the proliferative ventricular zone of the neocortex and
      hippocampus, as well as by a number of migrating and postmigratory neurons
      arranged into narrow radial stripes above the labeled progenitors. Thus, the
      transgene labels a subset of cortical progenitors and their progeny. Postnatally,
      radial clusters of beta-gal-positive neurons were discernible until postpartum
      day 10. At this age, the clusters were 250 to 500 microns wide, composed of
      neurons spanning all the cortical layers and exhibiting several neuronal
      phenotypes. These data suggest molecular heterogeneity of cortical progenitors
      and of the cohorts of postmitotic neurons originating from them, which implies
      intrinsic molecular mosaicism in both cortical progenitors and developing
      neurons. Furthermore, the data show that neurons committed to the expression of
      the transgene migrate along very narrow, radial stripes.

PMID- 8524828
TI  - The "DEAD box" protein DbpA interacts specifically with the peptidyltransferase
      center in 23S rRNA.
AB  - The Escherichia coli DEAD (Asp-Glu-Ala-Asp) box protein DbpA is a putative RNA
      helicase and established RNA-dependent ATPase and is the only member of the DEAD
      box protein family for which a specific RNA substrate, bacterial 23S rRNA, has
      been identified. We have investigated the nature of this specificity in depth and
      have localized by deletion mutagenesis and PCR a single region of 93 bases (bases
      2496-2588) in 23S rRNA that is both necessary and sufficient for complete
      activation of ATPase activity of DbpA. This target region forms part of the
      peptidyltransferase center and includes many bases involved in interaction with
      the 3' terminal adenosines of both A- and P-site tRNAs. Deletion of stem loops
      within the 93-base segment abolished ATPase activation. Similarly, point
      mutations that disrupt base pairing within stem structures ablated stimulation of
      ATPase activity. These data are consistent with roles for DbpA either in
      establishing and/or maintaining the correct three-dimensional structure of the
      peptidyltransferase center in 23S rRNA during ribosome assembly or in the
      peptidyltransferase reaction.

PMID- 8524829
TI  - The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine
      phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed
      in a tissue-specific manner and associate with the LAR-interacting protein LIP.1.
AB  - The transmembrane protein-tyrosine-phosphatases (PTPases) LAR, PTP delta, and PTP
      sigma each contain two intracellular PTPase domains and an extracellular region
      consisting of Ig-like and fibronectin type III-like domains. We describe the
      cloning and characterization of human PTP sigma (HPTP sigma) and compare the
      structure, alternative splicing, tissue distribution, and PTPase activity of LAR,
      HPTP delta, and HPTP sigma, as well their ability to associate with the
      intracellular coiled-coil LAR-interacting protein LIP.1. Overall, these three
      PTPases are structurally very similar, sharing 64% amino acid identity. Multiple
      isoforms of LAR, HPTP delta, and HPTP sigma appear to be generated by tissue
      specific alternative splicing of up to four mini-exon segments that encode
      peptides of 4-16 aa located in both the extracellular and intracellular regions.
      Alternative usage of these peptides varies depending on the tissue mRNA analyzed.
      Short isoforms of both HPTP sigma and HPTP delta were also detected that contain
      only four of the eight fibronectin type III-like domains. Northern blot analysis
      indicates that LAR and HPTP sigma are broadly distributed whereas HPTP delta
      expression is largely restricted to brain, as is the short HPTP sigma isoform
      containing only four fibronectin type III-like domains. LAR, HPTP delta, and HPTP
      sigma exhibit similar in vitro PTPase activities and all three interact with
      LIP.1, which has been postulated to recruit LAR to focal adhesions. Thus, these
      closely related PTPases may perform similar functions in various tissues.

PMID- 8524830
TI  - Specific mutations in the ligand binding domain selectively abolish the silencing
      function of human thyroid hormone receptor beta.
AB  - Although most nuclear hormone receptors are ligand-dependent transcriptional
      activators, certain members of this superfamily, such as thyroid hormone receptor
      (TR) and retinoic acid receptor (RAR), are involved in transcriptional
      repression. The silencing function of these receptors has been localized to the
      ligand binding domain (LBD). Previously, we demonstrated that overexpression of
      either the entire LBD or only the N-terminal region of the LBD (amino acids 168
      259) is able to inhibit the silencing activity of TR. From this result we
      postulated the existence of a limiting factor (corepressor) that is necessary for
      TR silencing activity. To support this hypothesis, we identified amino acids in
      the N-terminal region of the LBD of TR that are important for the corepressor
      interaction and for the silencing function of TR. The silencing activity of TR
      was unaffected by overexpression of the LBD of mutant TR (V174A/D177A),
      suggesting that valine at position 174 and/or aspartic acid at position 177 are
      important for corepressor interaction. This mutant receptor protein, V174/D177,
      also lost the ability to silence target genes, suggesting that these amino acids
      are important for silencing function. Control experiments indicate that this
      mutant TR maintains its wild-type hormone binding and transactivation functions.
      These findings further strengthen the idea that the N-terminal region of the LBD
      of TR interacts with a putative corepressor protein(s) to achieve silencing of
      basal gene transcription.

PMID- 8524831
TI  - Structural and functional analysis of pp70S6k.
AB  - The pp70/85-kDa S6 kinases, collectively referred to as pp70S6k, are thought to
      participate in transit through the G1 phase of the cell cycle. pp70S6k regulates
      the phosphorylation of the 40S ribosomal protein S6 and the transcription factor
      CREM tau. pp70S6k is regulated by serine/threonine phosphorylation, and although
      1-phosphatidylinositol 3-kinase and phospholipase C have been implicated as
      upstream regulators, the mechanism of activation and identity of the upstream
      pp70S6k kinases remain unknown. To improve our understanding of how this mitogen
      stimulated protein kinase is regulated by growth factors and the
      immunosuppressant rapamycin, we have initiated a structure/function analysis of
      pp70S6k. Our results indicate that both the N and C termini participate in the
      complex regulation of pp70S6k activity.

PMID- 8524832
TI  - Mapping by multifragment cloning in vivo.
AB  - An efficient method for mapping mutations is described in which hybrid genes,
      derived partly from mutant and partly from wild-type DNA, are obtained in vivo by
      homologous recombination of multiple fragments. The recombinants are formed in a
      strain in which their phenotypes are immediately apparent. This method was
      developed to identify changes that disrupt protein-protein interactions
      demonstrable by the two-hybrid system in yeast. However, it can be extended to
      any system where recombination is possible, provided an assay is available to
      distinguish between mutant and wild-type phenotypes.

PMID- 8524833
TI  - Isolation of yeast artificial chromosomes free of endogenous yeast chromosomes:
      construction of alternate hosts with defined karyotypic alterations.
AB  - An intrinsic feature of yeast artificial chromosomes (YACs) is that the cloned
      DNA is generally in the same size range (i.e., approximately 200-2000 kb) as the
      endogenous yeast chromosomes. As a result, the isolation of YAC DNA, which
      typically involves separation by pulsed-field gel electrophoresis, is frequently
      confounded by the presence of a comigrating or closely migrating endogenous yeast
      chromosome(s). We have developed a strategy that reliably allows the isolation of
      any YAC free of endogenous yeast chromosomes. Using recombination-mediated
      chromosome fragmentation, a set of Saccharomyces cerevisiae host strains was
      systematically constructed. Each strain contains defined alterations in its
      electrophoretic karyotype, which provide a large-size interval devoid of
      endogenous chromosomes (i.e., a karyotypic "window"). All of the constructed
      strains contain the kar1-delta 15 mutation, thereby allowing the efficient
      transfer of a YAC from its original host into an appropriately selected window
      strain using the kar1-transfer procedure. This approach provides a robust and
      efficient means to obtain relatively pure YAC DNA regardless of YAC size.

PMID- 8524834
TI  - Primary structure and functional expression of a cGMP-gated potassium channel.
AB  - Cyclic nucleotides modulate potassium (K) channel activity in many cells and are
      thought to act indirectly by inducing channel protein phosphorylation. Herein we
      report the isolation from rabbit of a gene encoding a K channel (Kcn1) that is
      specifically activated by cGMP and not by cAMP. Analysis of the deduced amino
      acid sequence (725 amino acids) indicates that, in addition to a core region that
      is highly homologous to Shaker K channels, Kcn1 also contains a cysteine-rich
      region similar to that of ligand-gated ion channels and a cyclic nucleotide
      binding region. Northern blot analysis detects gene expression in kidney, aorta,
      and brain. Kcn1 represents a class of K channels that may be specifically
      regulated by cGMP and could play an important role in mediating the effects of
      substances, such as nitric oxide, that increase intracellular cGMP.

PMID- 8524835
TI  - Protein kinase A-independent modulation of ion channels in the brain by cyclic
      AMP.
AB  - Ion channels underlying the electrical activity of neurons can be regulated by
      neurotransmitters via two basic mechanisms: ligand binding and covalent
      modification. Whereas neurotransmitters often act by binding directly to ion
      channels, the intracellular messenger cyclic AMP is thought usually to act
      indirectly, by activating protein kinase A, which in turn can phosphorylate
      channel proteins. Here we show that cyclic AMP, and transmitters acting via
      cyclic AMP, can act in a protein kinase A-independent manner in the brain. In
      hippocampal pyramidal cells, cyclic AMP and norepinephrine were found to cause a
      depolarization by enhancing the hyperpolarization-activated mixed cation current,
      IQ (also called Ih). This effect persisted even after protein kinase A activity
      was blocked, thus strongly suggesting a kinase-independent action of cyclic AMP.
      The modulation of this current by ascending monoaminergic fibers from the
      brainstem is likely to be a widespread mechanism, participating in the state
      control of the brain during arousal and attention.

PMID- 8524836
TI  - Crystal structure of the complex of a catalytic antibody Fab fragment with a
      transition state analog: structural similarities in esterase-like catalytic
      antibodies.
AB  - The x-ray structure of the complex of a catalytic antibody Fab fragment with a
      phosphonate transition-state analog has been determined. The antibody (CNJ206)
      catalyzes the hydrolysis of p-nitrophenyl esters with significant rate
      enhancement and substrate specificity. Comparison of this structure with that of
      the uncomplexed Fab fragment suggests hapten-induced conformational changes: the
      shape of the combining site changes from a shallow groove in the uncomplexed Fab
      to a deep pocket where the hapten is buried. Three hydrogen-bond donors appear to
      stabilize the charged phosphonate group of the hapten: two NH groups of the heavy
      (H) chain complementarity-determining region 3 (H3 CDR) polypeptide chain and the
      side-chain of histidine-H35 in the H chain (His-H35) in the H1 CDR. The combining
      site shows striking structural similarities to that of antibody 17E8, which also
      has esterase activity. Both catalytic antibody ("abzyme") structures suggest that
      oxyanion stabilization plays a significant role in their rate acceleration.
      Additional catalytic groups that improve efficiency are not necessarily induced
      by the eliciting hapten; these groups may occur because of the variability in the
      combining sites of different monoclonal antibodies that bind to the same hapten.

PMID- 8524837
TI  - Assembly of regularly spaced nucleosome arrays by Drosophila chromatin assembly
      factor 1 and a 56-kDa histone-binding protein.
AB  - To ascertain the mechanism by which nucleosomes are assembled by factors derived
      from Drosophila embryos, two proteins termed Drosophila chromatin assembly
      factors (CAFs) 1 and 4 (dCAF-1 and dCAF-4) were fractionated and purified from a
      Drosophila embryo extract. The assembly of chromatin by dCAF-1, dCAF-4, purified
      histones, ATP, and DNA is a process that generates regularly spaced nucleosomal
      arrays with a repeat length that resembles that of bulk native Drosophila
      chromatin and is not obligatorily coupled to DNA replication. The assembly of
      chromatin by dCAF-1 and dCAF-4 is nearly complete within 10 min. The dCAF-1
      activity copurified with the Drosophila version of chromatin assembly factor-1
      (CAF-1), a factor that has been found to be required for the assembly of
      chromatin during large tumor (T) antigen-mediated, simian virus 40 (SV40) origin
      dependent DNA replication. The dCAF-4 activity copurified with a 56-kDa core
      histone-binding protein that was purified to > 90% homogeneity.

PMID- 8524838
TI  - Specific activation in jun-transformed avian fibroblasts of a gene (bkj) related
      to the avian beta-keratin gene family.
AB  - We have analyzed differential gene expression in normal versus jun-transformed
      avian fibroblasts by using subtracted nucleic acid probes and differential
      nucleic acid hybridization techniques for the isolation of cDNA clones. One clone
      corresponded to a gene that was strongly expressed in a previously established
      quail (Coturnix japonica) embryo fibroblast line (VCD) transformed by a chimeric
      jun oncogene but whose expression was undetectable in normal quail embryo
      fibroblasts. Furthermore, the gene was expressed in quail or chicken fibroblast
      cultures that were freshly transformed by retroviral constructs carrying various
      viral or cellular jun alleles and in chicken fibroblasts transformed by the avian
      retrovirus ASV17 carrying the original viral v-jun allele. However, its
      expression was undetectable in a variety of established avian cell lines or
      freshly prepared avian fibroblast cultures transformed by other oncogenes or a
      chemical carcinogen. The nucleotide and deduced amino acid sequences of the cDNA
      clone were not identical to any sequence entries in the data bases but revealed
      significant similarities to avian beta-keratin genes; the highest degree of amino
      acid sequence identity was 63%. The gene, which we termed bkj, may represent a
      direct or indirect target for jun function.

PMID- 8524839
TI  - cAMP-dependent SOS induction and mutagenesis in resting bacterial populations.
AB  - The inducible SOS system increases the survival of bacteria exposed to DNA
      damaging agents by increasing the capacity of error-free and error-prone DNA
      repair systems. The inducible mutator effect is expected to contribute to the
      adaptation of bacterial populations to these adverse life conditions by
      increasing their genetic variability. The evolutionary impact of the SOS system
      would be even greater if it was also induced under conditions common in nature,
      such as in resting bacterial populations. The results presented here show that
      SOS induction and mutagenesis do occur in bacteria in aging colonies on agar
      plates. The observed SOS induction and mutagenesis are controlled by the LexA
      repressor and are RecA- and cAMP-dependent.

PMID- 8524840
TI  - Inferring identify from DNA profile evidence.
AB  - The controversy over the interpretation of DNA profile evidence in forensic
      identification can be attributed in part to confusion over the mode(s) of
      statistical inference appropriate to this setting. Although there has been
      substantial discussion in the literature of, for example, the role of population
      genetics issues, few authors have made explicit the inferential framework which
      underpins their arguments. This lack of clarity has led both to unnecessary
      debates over ill-posed or inappropriate questions and to the neglect of some
      issues which can have important consequences. We argue that the mode of
      statistical inference which seems to underlie the arguments of some authors,
      based on a hypothesis testing framework, is not appropriate for forensic
      identification. We propose instead a logically coherent framework in which, for
      example, the roles both of the population genetics issues and of the
      nonscientific evidence in a case are incorporated. Our analysis highlights
      several widely held misconceptions in the DNA profiling debate. For example, the
      profile frequency is not directly relevant to forensic inference. Further, very
      small match probabilities may in some settings be consistent with acquittal.
      Although DNA evidence is typically very strong, our analysis of the coherent
      approach highlights situations which can arise in practice where alternative
      methods for assessing DNA evidence may be misleading.

PMID- 8524841
TI  - The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for
      transformation.
AB  - The leukemogenic tyrosine kinase fusion protein Bcr-Abl activates a Ras-dependent
      pathway required for transformation. To examine subsequent signal transduction
      events we measured the effect of Bcr-Abl on two mitogen-activated protein kinase
      (MAPK) cascades--the extracellular signal-regulated kinase (ERK) pathway and the
      Jun N-terminal kinase (JNK) pathway. We find that Bcr-Abl primarily activates JNK
      in fibroblasts and hematopoietic cells. Bcr-Abl enhances JNK function as measured
      by transcription from Jun responsive promoters and requires Ras, MEK kinase
      (MAPK/ERK kinase kinase), and JNK to do so. Dominant-negative mutants of c-Jun,
      which inhibit the endpoint of the JNK pathway, impair Bcr-Abl transforming
      activity. These findings implicate the JNK pathway in transformation by a human
      leukemia oncogene.

PMID- 8524842
TI  - A single amino acid in gamma-aminobutyric acid rho 1 receptors affects
      competitive and noncompetitive components of picrotoxin inhibition.
AB  - A class of bicuculline-insensitive gamma-aminobutyric acid (GABA) receptors,
      GABAC, has been identified in retina. Several lines of evidence indicate that
      GABAC receptors are formed partially or wholly of GABA rho subunits. These
      receptors generate a Cl- current in response to GABA but differ from GABAA
      receptors in a number of ways. Picrotoxin, widely accepted as a noncompetitive
      antagonist of GABAA receptors, displays competitive and noncompetitive antagonism
      of GABAC receptors in perch and bovine retina and GABA rho 1 receptors expressed
      in Xenopus oocytes. The aim of this study was to identify the molecular basis of
      the two components of picrotoxin inhibition of GABA rho 1 receptors. By using a
      domain-swapping and mutagenesis strategy, a difference in picrotoxin sensitivity
      between rho 1 and rho 2 receptors was localized to a single amino acid in the
      putative second transmembrane domain. Substitution of this amino acid with
      residues found in the analogous position in highly picrotoxin-sensitive glycine
      alpha and GABAA subunits increased the sensitivity of rho 1 mutants 10- to 500
      fold. Importantly, the competitive component of picrotoxin inhibition of the rho
      1 mutant receptors was almost eliminated. These findings demonstrate that an
      amino acid in the putative channel domain of GABA rho 1 receptors influences
      picrotoxin sensitivity and mediates agonist binding by an allosteric mechanism.

PMID- 8524843
TI  - Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with a
      methionine residue critical for picrotoxinin channel block.
AB  - Ionotropic receptors for gamma-aminobutyric acid (GABA) are important to
      inhibitory neurotransmission in the mammalian retina, mediating GABAA and GABAC
      responses. In many species, these responses are blocked by the convulsant
      picrotoxinin (PTX), although the mechanism of block is not fully understood. In
      contrast, GABAC responses in the rat retina are extremely resistant to PTX. We
      hypothesized that this difference could be explained by molecular
      characterization of the receptors underlying the GABAC response. Here we report
      the cloning of two rat GABA receptor subunits, designated r rho 1 and r rho 2
      after their previously identified human homologues. When coexpressed in Xenopus
      oocytes, r rho 1/r rho 2 heteromeric receptors mimicked PTX-resistant GABAC
      responses of the rat retina. PTX resistance is apparently conferred in native
      heteromeric receptors by r rho 2 subunits since homomeric r rho 1 receptors were
      sensitive to PTX; r rho 2 subunits alone were unable to form functional homomeric
      receptors. Site-directed mutagenesis confirmed that a single amino acid residue
      in the second membrane-spanning region (a methionine in r rho 2 in place of a
      threonine in r rho 1) is the predominant determinant of PTX resistance in the rat
      receptor. This study reveals not only the molecular mechanism underlying PTX
      blockade of GABA receptors but also the heteromeric nature of native receptors in
      the rat retina that underlie the PTX-resistant GABAC response.

PMID- 8524844
TI  - The specificity of the transforming growth factor beta receptor kinases
      determined by a spatially addressable peptide library.
AB  - Type I and II receptors for the transforming growth factor beta (TGF-beta) are
      transmembrane serine/threonine kinases that are essential for TGF-beta signaling.
      However, little is known about their in vivo substrates or signal transduction
      pathways. To determine the substrate specificity of these kinases, we developed
      combinatorial peptide libraries synthesized on a hydrophilic matrix that is
      easily accessible to proteins in aqueous solutions. When we subjected these
      libraries to phosphorylation by the cAMP-dependent protein kinase, we obtained
      the optimal peptide sequence RRXS (I/L/V), in perfect agreement with the
      substrate sequence deduced from mutagenesis and crystal structure analyses. By
      using the same libraries, we showed that the optimal substrate peptide for both
      the type I and II TGF-beta receptors was KKKKKK(S/T)XXX. Since the two kinases
      are thought to play different roles in intracellular signal transduction, it was
      a surprise to find that they have almost identical substrate specificity. Our
      method is direct, sensitive, and simple and provides information about the kinase
      specificity for all the amino acid residues at each position.

PMID- 8524845
TI  - Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and
      a previously unrecognized alpha-mannosidase IIx isozyme.
AB  - Golgi alpha-mannosidase II (alpha-MII) is an enzyme involved in the processing of
      N-linked glycans. Using a previously isolated murine cDNA clone as a probe, we
      have isolated cDNA clones encompassing the human alpha-MII cDNA open reading
      frame and initiated isolation of human genomic clones. During the isolation of
      genomic clones, genes related to that encoding alpha-MII were isolated. One such
      gene was found to encode an isozyme, designated alpha-MIIx. A 5-kb cDNA clone
      encoding alpha-MIIx was then isolated from a human melanoma cDNA library.
      However, comparison between alpha-MIIx and alpha-MII cDNAs suggested that the
      cloned cDNA encodes a truncated polypeptide with 796 amino acid residues, while
      alpha-MII consists of 1144 amino acid residues. To reevaluate the sequence of
      alpha-MIIx cDNA, polymerase chain reaction (PCR) was performed with lymphocyte
      mRNAs. Comparison of the sequence of PCR products with the alpha-MIIx genomic
      sequence revealed that alternative splicing of the alpha-MIIx transcript can
      result in an additional transcript encoding a 1139-amino acid polypeptide.
      Northern analysis showed transcription of alpha-MIIx in various tissues,
      suggesting that the alpha-MIIx gene is a housekeeping gene. COS cells transfected
      with alpha-MIIx cDNA containing the full-length open reading frame showed an
      increase of alpha-mannosidase activity. The alpha-MIIx gene was mapped to human
      chromosome 15q25, whereas the alpha-MII gene was mapped to 5q21-22.

PMID- 8524846
TI  - Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin
      (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an
      active dimer.
AB  - Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only
      in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To
      understand the structure-activity relationships of human iNOS, we constitutively
      expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector.
      These cells are deficient in de novo H4B biosynthesis and the role of H4B in the
      expression and assembly of active iNOS in an intact cell system could be studied.
      In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells
      grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1
      and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis
      correlated with an increase in intracellular H4B but no increase in iNOS protein.
      Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in
      cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In
      all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from
      H4B-deficient cells exhibited little iNOS activity but acquired activity during a
      60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of
      citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis
      activity was associated with conversion of monomers into dimeric iNOS during the
      incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B
      plays a critical role in promoting dimerization in intact cells. This reveals a
      post-translational mechanism by which intracellular H4B can regulate iNOS
      expression.

PMID- 8524847
TI  - Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase
      identifies a novel motif for dual acylation and subcellular targeting.
AB  - The endothelial nitric oxide synthase (ec-NOS) plays a key role in the
      transduction of signals from the bloodstream to the underlying smooth muscle.
      ecNOS undergoes a complex series of covalent modifications, including
      myristoylation and palmitoylation, which appear to play a role in ecNOS membrane
      association. Mutagenesis of the myristoylation site, which prevents both
      myristoylation and palmitoylation, blocks ecNOS targeting to cell membranes.
      Further, as described for some G-protein alpha subunits, both membrane
      association and palmitoylation of ecNOS are dynamically regulated: in response to
      agonists, the enzyme undergoes partial redistribution to the cell cytosol
      concomitant with depalmitoylation. To clarify the role of palmitoylation in
      determining ecNOS subcellular localization, we have constructed palmitoylation
      deficient mutants of ecNOS. Serine was substituted for cysteine at two potential
      palmitoylation sites (Cys-15 and Cys-26) by site-directed mutagenesis.
      Immunoprecipitation of ecNOS mutants following cDNA transfection and biosynthetic
      labeling with [3H]palmitate revealed that mutagenesis of either cysteine residue
      attenuated palmitoylation, whereas replacement of both residues completely
      eliminated palmitoylation. Analysis of N-terminal deletion mutations of ecNOS
      demonstrated that the region containing these two cysteine residues is both
      necessary and sufficient for enzyme palmitoylation. The cysteines thus identified
      as the palmitoylation sites for ecNOS are separated by an unusual (Gly-Leu)5
      sequence and appear to define a sequence motif for dual acylation. We analyzed
      the subcellular distribution of ecNOS mutants by differential ultracentrifugation
      and found that mutagenesis of the ecNOS palmitoylation sites markedly reduced
      membrane association of the enzyme. These results document that ecNOS
      palmitoylation is an important determinant for the subcellular distribution of
      ecNOS and identify a new motif for the reversible palmitoylation of signaling
      proteins.

PMID- 8524848
TI  - A role for Rho in Ras transformation.
AB  - The small GTP-binding proteins Rac and Rho are key elements in the signal
      transduction pathways respectively controlling the formation of lamellipodia and
      stress fibers induced by growth factors or oncogenic Ras. We recently reported
      that Rac function is necessary for Ras transformation and that expression of
      constitutively activated Rac1 is sufficient to cause malignant transformation. We
      now show that, although expression of constitutively activated V14-RhoA in Rat 1
      fibroblasts does not cause transformation on its own, it strongly cooperates with
      constitutively active RafCAAX in focus-formation assays in NIH 3T3 cells.
      Furthermore, dominant-negative N19-RhoA inhibits focus formation by V12-H-Ras and
      RafCAAX in NIH 3T3 cells, and stable coexpression of N19-RhoA and V12-H-Ras in
      Rat1 fibroblasts reverts Ras transformation. Interestingly, stress fiber
      formation is inhibited in V12-H-Ras lines and restored by coexpression of N19
      RhoA. We conclude that Rho drives at least two separate pathways, one that
      induces stress fiber formation and another one that is important for
      transformation by oncogenic Ras.

PMID- 8524849
TI  - Arabidopsis mutants deficient in T-DNA integration.
AB  - Arabidopsis thaliana mutants originally isolated as hypersensitive to irradiation
      were screened for the ability to be transformed by Agrobacterium transferred DNA
      (T-DNA). One of four UV-hypersensitive mutants and one of two gamma
      hypersensitive mutants tested showed a significant reduction in the frequency of
      stable transformants compared with radioresistant controls. In a transient assay
      for T-DNA transfer independent of genomic integration, both mutant lines took up
      and expressed T-DNA as efficiently as parental lines. These lines are therefore
      deficient specifically in stable T-DNA integration and thus provide direct
      evidence for the role of a plant function in that process. As radiation
      hypersensitivity suggests a deficiency in repair of DNA damage, that plant
      function may be one that is also involved in DNA repair, possibly, from other
      evidence, in repair of double-strand DNA breaks.

PMID- 8524850
TI  - Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces
      cerevisiae, has a dual role in S-phase progression and at a cell cycle
      checkpoint.
AB  - DPB11, a gene that suppresses mutations in two essential subunits of
      Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was
      isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene
      revealed an open reading frame predicting an 87-kDa protein. This protein is
      homologous to the Schizosaccharomyces pombe rad4+/cut5+ gene product that has a
      cell cycle checkpoint function. Disruption of DPB11 is lethal, indicating that
      DPB11 is essential for cell proliferation. In thermosensitive dpb11-1 mutant
      cells, S-phase progression is defective at the nonpermissive temperature,
      followed by cell division with unequal chromosomal segregation accompanied by
      loss of viability.dpb11-1 is synthetic lethal with any one of the dpb2-1, pol2
      11, and pol2-18 mutations at all temperatures. Moreover, dpb11 cells are
      sensitive to hydroxyurea, methyl methanesulfonate, and UV irradiation. These
      results strongly suggest that Dpb11 is a part of the DNA polymerase II complex
      during chromosomal DNA replication and also acts in a checkpoint pathway during
      the S phase of the cell cycle to sense stalled DNA replication.

PMID- 8524851
TI  - Susceptibility of cloned K+ channels to reactive oxygen species.
AB  - Free radical-induced oxidant stress has been implicated in a number of
      physiological and pathophysiological states including ischemia and reperfusion
      induced dysrhythmia in the heart, apoptosis of T lymphocytes, phagocytosis, and
      neurodegeneration. We have studied the effects of oxidant stress on the native K+
      channel from T lymphocytes and on K+ channels cloned from cardiac, brain, and T
      lymphocyte cells and expressed in Xenopus oocytes. The activity of three Shaker
      K+ channels (Kv1.3, Kv1.4, and Kv1.5), one Shaw channel (Kv3.4), and one inward
      rectifier K+ channel (IRK3) was drastically inhibited by photoactivation of rose
      bengal, a classical generator of reactive oxygen species. Other channel types
      (such as Shaker K+ channel Kv1.2, Shab channels Kv2.1 and Kv2.2, Shal channel
      Kv4.1, inward rectifiers IRK1 and ROMK1, and hIsK) were completely resistant to
      this treatment. On the other hand tert-butyl hydroperoxide, another generator of
      reactive oxygen species, removed the fast inactivation processes of Kv1.4 and
      Kv3.4 but did not alter other channels. Xanthine/xanthine oxidase system had no
      effect on all channels studied. Thus, we show that different types of K+ channels
      are differently modified by reactive oxygen species, an observation that might be
      of importance in disease states.

PMID- 8524852
TI  - Topoisomerase IV is a target of quinolones in Escherichia coli.
AB  - We have demonstrated that, in Escherichia coli, quinolone antimicrobial agents
      target topoisomerase IV (topo IV). The inhibition of topo IV becomes apparent
      only when gyrase is mutated to quinolone resistance. In such mutants, these
      antibiotics caused accumulation of replication catenanes, which is diagnostic of
      a loss of topo IV activity. Mutant forms of topo IV provided an additional 10
      fold resistance to quinolones and prevented drug-induced catenane accumulation.
      Drug inhibition of topo IV differs from that of gyrase. (i) Wild-type topo IV is
      not dominant over the resistant allele. (ii) Inhibition of topo IV leads to only
      a slow stop in replication. (iii) Inhibition of topo IV is primarily
      bacteriostatic. These differences may result from topo IV acting behind the
      replication fork, allowing for repair of drug-induced lesions. We suggest that
      this and a slightly higher intrinsic resistance of topo IV make it secondary to
      gyrase as a quinolone target. Our results imply that the quinolone binding
      pockets of gyrase and topo IV are similar and that substantial levels of drug
      resistance require mutations in both enzymes.

PMID- 8524853
TI  - Recovery of respiration following the SOS response of Escherichia coli requires
      RecA-mediated induction of 2-keto-4-hydroxyglutarate aldolase.
AB  - Agents that damage DNA in Escherichia coli or interfere with its replication
      induce DNA repair and mutagenesis via the SOS response. This well-known activity
      is regulated by the RecA protein and the LexA repressor. Following repair or
      bypass of the DNA lesion, the cell returns to its resting state by a largely
      unknown process. We found that 2-keto-4-hydroxyglutarate aldolase (4-hydroxy-2
      oxoglutarate aldolase; EC 4.1.3.16) is necessary for the recovery of respiration
      and that it is regulated by the SOS response. This protein was induced by DNA
      damaging agents. Induction required RecA activation. When the LexA regulon was
      repressed, activation of RecA was not sufficient for induction, indicating the
      requirement for an additional protein under LexA control. Finally, a mutant in
      the corresponding hga gene was UV sensitive. 2-Keto-4-hydroxyglutarate aldolase
      also plays a role in respiratory metabolic pathways, which suggests a mechanism
      for respiration resumption during the termination of the SOS response.

PMID- 8524854
TI  - Human neoplasms elicit multiple specific immune responses in the autologous host.
AB  - Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and
      Hodgkin disease in Escherichia coli and screening for clones reactive with high
      titer IgG antibodies in autologous patient serum lead to the discovery of at
      least four antigens with a restricted expression pattern in each tumor. Besides
      antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase,
      numerous additional antigens that were overexpressed or specifically expressed in
      tumors of the same type were identified. Sequence analyses suggest that many of
      these molecules, besides being the target of a specific immune response, might be
      of relevance for tumor growth. Antibodies to a given antigen were usually
      confined to patients with the same tumor type. The unexpected frequency of human
      tumor antigens, which can be readily defined at the molecular level by the
      serological analysis of autologous tumor cDNA expression cloning, indicates that
      human neoplasms elicit multiple specific immune responses in the autologous host
      and provides diagnostic and therapeutic approaches to human cancer.

PMID- 8524855
TI  - CD38 ligation induces tyrosine phosphorylation of Bruton tyrosine kinase and
      enhanced expression of interleukin 5-receptor alpha chain: synergistic effects
      with interleukin 5.
AB  - Mouse CD38 has been implicated in the regulation of both B-cell proliferation and
      protection of B cells from irradiation-induced apoptosis. CD38 ligation on B
      cells by CS/2, an anti-mouse CD38 monoclonal antibody, induced proliferation, IgM
      secretion, and tyrosine phosphorylation of Bruton tyrosine kinase in B cells from
      wild-type mice. B cells from X chromosome-linked immunodeficient mice did not
      respond at all to anti-CD38 antibody, although CD38 expression on these B cells
      was comparable to that on wild-type B cells. We infer from these results that
      Bruton tyrosine kinase activation is involved in B-cell triggering after cross
      linkage of CD38. Analysis of the synergistic effects of various cytokines with
      CD38 ligation on B-cell activation revealed that interleukin 5 (IL-5) showed the
      most potent effect on B-cell proliferation, Blimp1 gene expression, and IgM
      production. These synergistic effects were not seen with B cells from X
      chromosome-linked immunodeficient mice. Flow cytometry analysis revealed that
      CD38 ligation increased surface expression of the IL-5-receptor alpha chain on B
      cells. These data indicate that CD38 ligation increases IL-5 receptor alpha
      expression and synergizes with IL-5 to enhance Blimp1 expression and IgM
      synthesis.

PMID- 8524856
TI  - Localization of choline acetyltransferase in rat peripheral sympathetic neurons
      and its coexistence with nitric oxide synthase and neuropeptides.
AB  - Indirect immunofluorescence methods using a mouse monoclonal antibody raised to
      rat choline acetyltransferase (ChAT) revealed dense networks of ChAT
      immunoreactive fibers in the superior cervical ganglion, the stellate ganglion,
      and the celiac superior mesenteric ganglion of the rat. Numerous and single ChAT
      immunoreactive cell bodies were observed in the stellate and superior cervical
      ganglia, respectively. The majority of ChAT-immunoreactive fibers in the stellate
      and superior cervical ganglia were nitric oxide synthase (NOS) positive. Some
      ChAT-immunoreactive fibers contained enkephalin-like immunoreactivity. Virtually
      all ChAT-positive cell bodies in the stellate ganglion were vasoactive intestinal
      polypeptide (VIP)-positive, and some were calcitonin gene-related peptide (CGRP)
      positive. After transection of the cervical sympathetic trunk almost all ChAT-
      and NOS-positive fibers and most enkephalin- and CGRP-positive fibers disappeared
      in the superior cervical ganglion. The results suggest that most preganglionic
      fibers are cholinergic and that the majority of these in addition can release
      nitric oxide, some enkephalin, and a few CGRP. Acetylcholine, VIP, and CGRP are
      coexisting messenger molecules in some postganglionic sympathetic neurons.

PMID- 8524857
TI  - MyoD forms micelles which can dissociate to form heterodimers with E47:
      implications of micellization on function.
AB  - MyoD is a member of a family of DNA-binding transcription factors that contain a
      helix-loop-helix (HLH) region involved in protein-protein interactions. In
      addition to self-association and DNA binding, MyoD associates with a number of
      other HLH-containing proteins, thereby modulating the strength and specificity of
      its DNA binding. Here, we examine the interactions of full-length MyoD with
      itself and with an HLH-containing peptide portion of an E2A gene product, E47-96.
      Analytical ultracentrifugation reveals that MyoD forms micelles that contain more
      than 100 monomers and are asymmetric and stable up to 36 degrees C. The critical
      micelle concentration increases slightly with temperature, but micelle size is
      unaffected. The micelles are in reversible equilibrium with monomer. Addition of
      E47-96 results in the stoichiometric formation of stable MyoD-E47-96 heterodimers
      and the depletion of micelles. Micelle formation effectively holds the
      concentration of free MyoD constant and equal to the critical micelle
      concentration. In the presence of micelles, the extent of all interactions
      involving free MyoD is independent of the total MyoD concentration and
      independent of one another. For DNA binding, the apparent relative specificity
      for different sites can be affected. In general, heterodimer-associated
      activities will depend on the self-association behavior of the partner protein.

PMID- 8524858
TI  - Characterization of repetitive DNA in the Mycoplasma genitalium genome: possible
      role in the generation of antigenic variation.
AB  - We have characterized a family of repetitive DNA elements with homology to the
      MgPa cellular adhesion operon of Mycoplasma genitalium, a bacterium that has the
      smallest known genome of any free-living organism. One element, 2272 bp in length
      and flanked by DNA with no homology to MgPa, was completely sequenced. At least
      four others were partially sequenced. The complete element is a composite of six
      regions. Five of these regions show sequence similarity with nonadjacent segments
      of genes of the MgPa operon. The sixth region, located near the center of the
      element, is an A+T-rich sequence that has only been found in this repeat family.
      Open reading frames are present within the five individual regions showing
      sequence homology to MgPa and the adjacent open reading frame 3 (ORF3) gene.
      However, termination codons are found between adjacent regions of homology to the
      MgPa operon and in the A+T-rich sequence. Thus, these repetitive elements do not
      appear to be directly expressible protein coding sequences. The sequence of one
      region from five different repetitive elements was compared with the homologous
      region of the MgPa gene from the type strain G37 and four newly isolated M.
      genitalium strains. Recombination between repetitive elements of strain G37 and
      the MgPa operon can explain the majority of polymorphisms within our partial
      sequences of the MgPa genes of the new isolates. Therefore, we propose that the
      repetitive elements of M. genitalium provide a reservoir of sequence that
      contributes to antigenic variation in proteins of the MgPa cellular adhesion
      operon.

PMID- 8524859
TI  - An anatomical substrate for experience-dependent plasticity of the rat barrel
      field cortex.
AB  - The objective of this study was to examine the influence of sensory experience on
      the synaptic circuitry of the cortex. For this purpose, the quantitative
      distribution of the overall and of the gamma-aminobutyric acid (GABA) population
      of synaptic contacts was investigated in each layer of the somatosensory barrel
      field cortex of rats which were sensory deprived from birth by continuously
      removing rows of whiskers. Whereas there were no statistically significant
      changes in the quantitative distribution of the overall synaptic population, the
      number and proportion of GABA-immunopositive synaptic contacts were profoundly
      altered in layer IV of the somatosensory cortex of sensory-deprived animals.
      These changes were attributable to a specific loss of as many as two-thirds of
      the GABA contacts targeting dendritic spines. Thus, synaptic contacts made by
      GABA terminals in cortical layer IV and, in particular, those targeting dendritic
      spines represent a structural substrate of experience-dependent plasticity.
      Furthermore, since in this model of cortical plasticity the neuronal receptive
      field properties are known to be affected, we propose that the inhibitory control
      of dendritic spines is essential for the elaboration of these functional
      properties.

PMID- 8524860
TI  - Molecular determinants of drug access to the receptor site for antiarrhythmic
      drugs in the cardiac Na+ channel.
AB  - The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to
      their voltage- and frequency-dependent block of Na+ channels. Quaternary local
      anesthetic analogs such as QX-314, which are permanently charged and membrane
      impermeant, effectively block cardiac Na+ channels when applied from either side
      of the membrane but block neuronal Na+ channels only from the intracellular side.
      This difference in extracellular access to QX-314 is retained when rat brain rIIA
      Na+ channel alpha subunits and rat heart rH1 Na+ channel alpha subunits are
      expressed transiently in tsA-201 cells. Amino acid residues in transmembrane
      segment S6 of homologous domain IV (IVS6) of Na+ channel alpha subunits have
      important effects on block by local anesthetic drugs. Although five amino acid
      residues in IVS6 differ between brain rIIA and cardiac rH1, exchange of these
      amino acid residues by site-directed mutagenesis showed that only conversion of
      Thr-1755 in rH1 to Val as in rIIA was sufficient to reduce the rate and extent of
      block by extracellular QX-314 and slow the escape of drug from closed channels
      after use-dependent block. Tetrodotoxin also reduced the rate of block by
      extracellular QX-314 and slowed escape of bound QX-314 via the extracellular
      pathway in rH1, indicating that QX-314 must move through the pore to escape. QX
      314 binding was inhibited by mutation of Phe-1762 in the local anesthetic
      receptor site of rH1 to Ala whether the drug was applied extracellularly or
      intracellularly. Thus, QX-314 binds to a single site in the rH1 Na+ channel alpha
      subunit that contains Phe-1762, whether it is applied from the extracellular or
      intracellular side of the membrane. Access to that site from the extracellular
      side of the pore is determined by the amino acid at position 1755 in the rH1
      cardiac Na+ channel.

PMID- 8524861
TI  - Differential sensitivity of stilbenedisulfonates in their reaction with band 3 HT
      (Pro-868-->Leu).
AB  - Band 3 HT (Pro-868-->Leu) is a mutant anion exchange protein which has several
      phenotypic characteristics, including a 2- to 3-fold larger Vmax, and reduced
      covalent binding of the anion transport inhibitor 4,4'
      diisothiocyanodihydrostilbene-2,2'-disulfonate (H2DIDS). We have used
      fluorescence kinetic methods to study inhibitor binding to band 3 to determine if
      the point mutation in band 3 HT produces localized or wide-spread conformational
      changes within the membrane-bound domain of this transporter. Our results show
      that covalent binding of H2DIDS by band 3 HT is slower by a factor of 10 to 20
      compared with the wild-type protein. In contrast, no such difference in the
      kinetics was observed for covalent binding of 4,4'-diisothiocyanostilbene-2,2'
      disulfonate (DIDS). In addition, the kinetics of H2DIDS release from band 3 HT
      was abnormal, while the kinetics of 4,4'-dibenzamidostilbene-2,2'-disulfonate
      (DBDS) release showed no difference when compared with the wild-type protein. We
      conclude that substitution of leucine for proline at position 868 does not
      perturb the structure of "lysine A" in the membrane-bound domain of band 3 but
      rather produces an apparently localized conformational change in the C-terminal
      subdomain of the protein which alters H2DIDS affinity. When combined with the
      observation of an increased Vmax, these results suggest that protein structural
      changes at position 868 influence a turnover step in the transport cycle.

PMID- 8524862
TI  - Evidence for DNA phosphate backbone alkylation and cleavage by pyrrolo[1,2
      a]benzimidazoles: small molecules capable of causing base-pair-specific
      phosphodiester bond hydrolysis.
AB  - This report presents evidence that a reduced pyrrolo[1,2-a]benzimidazole (PBI)
      cleaves DNA as a result of phosphate alkylation followed by hydrolysis of the
      resulting phosphate triester. The base-pair specificity of the phosphate
      alkylation results from Hoogsteen-type hydrogen bonding of the reduced PBI in the
      major groove at only A.T and G.C base pairs. Alkylated phosphates were detected
      by 31P NMR and the cleavage products were detected by 1H NMR and HPLC. Evidence
      is also presented that a reduced PBI interacts with DNA in the major groove
      rather than in the minor groove or by intercalation.

PMID- 8524863
TI  - Analysis of RNA-binding proteins by in vitro genetic selection: identification of
      an amino acid residue important for locking U1A onto its RNA target.
AB  - An in vitro genetic system was developed as a rapid means for studying the
      specificity determinants of RNA-binding proteins. This system was used to
      investigate the origin of the RNA-binding specificity of the mammalian
      spliceosomal protein U1A. The U1A domain responsible for binding to U1 small
      nuclear RNA was locally mutagenized and displayed as a combinatorial library on
      filamentous bacteriophage. Affinity selection identified four U1A residues in the
      mutagenized region that are important for specific binding to U1 hairpin II. One
      of these residues (Leu-49) disproportionately affects the rates of binding and
      release and appears to play a critical role in locking the protein onto the RNA.
      Interestingly, a protein variant that binds more tightly than U1A emerged during
      the selection, showing that the affinity of U1A for U1 RNA has not been optimized
      during evolution.

PMID- 8524864
TI  - Core promoter-specific function of a mutant transcription factor TFIID defective
      in TATA-box binding.
AB  - In conjunction with other general initiation factors, the TATA box-binding
      protein (TBP) can direct basal transcription by RNA polymerase II from TATA
      containing promoters, but its stable interaction with TBP-associated factors
      (TAFs) in the TFIID complex is required both for activator-dependent
      transcription and for basal transcription directed by an initiator element. We
      have generated a TATA-binding-defective TFIID complex containing an amino acid
      substitution in the DNA-binding surface of its TBP subunit. This mutated TFIID is
      defective in both basal and activated transcription from core promoters
      containing only a TATA box but supports transcription from initiator-containing
      promoters independently of the presence or absence of a TATA sequence. Our
      results show that a functional initiator element is needed to bypass the
      requirement for an active TATA DNA-binding surface in TFIID and imply that gene
      specific transcription can be achieved by modulating distinct core promoter
      specific TFIID functions--e.g., TBP-TATA versus TAF-initiator interactions.

PMID- 8524865
TI  - Ascorbic acid is essential for the release of insulin from scorbutic guinea pig
      pancreatic islets.
AB  - Pancreatic islets from young normal and scorbutic male guinea pigs were examined
      for their ability to release insulin when stimulated with elevated D-glucose.
      Islets from normal guinea pigs released insulin in a D-glucose-dependent manner
      showing a rapid initial secretion phase and three secondary secretion waves
      during a 120-min period. Islets from scorbutic guinea pigs failed to release
      insulin during the immediate period, and only delayed and decreased responses
      were observed over the 40-60 min after D-glucose elevation. Insulin release from
      scorbutic islets was greatly elevated if 5 mM L-ascorbic acid 2-phosphate was
      supplemented in the perifusion medium during the last 60 min of perifusion. When
      5 mM L-ascorbic acid 2-phosphate was added to the perifusion medium concurrently
      with elevation of medium D-glucose, islets from scorbutic guinea pigs released
      insulin as rapidly as control guinea pig islets and to a somewhat greater extent.
      L-Ascorbic acid 2-phosphate without elevated D-glucose had no effect on insulin
      release by islets from normal or scorbutic guinea pigs. The pancreas from
      scorbutic guinea pigs contained 2.4 times more insulin than that from control
      guinea pigs, suggesting that the decreased insulin release from the scorbutic
      islets was not due to decreased insulin synthesis but due to abnormal insulin
      secretion.

PMID- 8524866
TI  - Inflammatory skin disease in transgenic mice that express high levels of
      interleukin 1 alpha in basal epidermis.
AB  - Resting epidermal keratinocytes contain large amounts of interleukin 1 (IL-1),
      but the function of this cytokine in the skin remains unclear. To further define
      the role of IL-1 in cutaneous biology, we have generated two lines of transgenic
      mice (TgIL-1.1 and TgIL-1.2) which overexpress IL-1 alpha in basal keratinocytes.
      There was high-level tissue-specific expression of transgene mRNA and protein and
      large quantities of IL-1 alpha were liberated into the circulation from epidermis
      in both lines. TgIL-1.1 mice, which had the highest level of transgene
      expression, developed a spontaneous skin disease characterized by hair loss,
      scaling, and focal inflammatory skin lesions. Histologically, nonlesional skin of
      these animals was characterized by hyperkeratosis and a dermal mononuclear cell
      infiltrate of macrophage/monocyte lineage. Inflammatory lesions were marked by a
      mixed cellular infiltrate, acanthosis, and, in some cases, parakeratosis. These
      findings confirm the concept of IL-1 as a primary cytokine, release of which is
      able to initiate and localize an inflammatory reaction. Furthermore, these mice
      provide the first definitive evidence that inflammatory mediators can be released
      from the epidermis to enter the systemic circulation and thereby influence, in a
      paracrine or endocrine fashion, a wide variety of other cell types.

PMID- 8524867
TI  - Survival and differentiation of adult neuronal progenitor cells transplanted to
      the adult brain.
AB  - The dentate gyrus of the hippocampus is one of the few areas of the adult brain
      that undergoes neurogenesis. In the present study, cells capable of proliferation
      and neurogenesis were isolated and cultured from the adult rat hippocampus. In
      defined medium containing basic fibroblast growth factor (FGF-2), cells can
      survive, proliferate, and express neuronal and glial markers. Cells have been
      maintained in culture for 1 year through multiple passages. These cultured adult
      cells were labeled in vitro with bromodeoxyuridine and adenovirus expressing beta
      galactosidase and were transplanted to the adult rat hippocampus. Surviving cells
      were evident through 3 months postimplantation with no evidence of tumor
      formation. Within 2 months postgrafting, labeled cells were found in the dentate
      gyrus, where they differentiated into neurons only in the intact region of the
      granule cell layer. Our results indicate that FGF-2 responsive progenitors can be
      isolated from the adult hippocampus and that these cells retain the capacity to
      generate mature neurons when grafted into the adult rat brain.

PMID- 8524868
TI  - Haploidy and androgenesis in Drosophila.
AB  - Adrogenesis, development from paternal but not maternal chromosomes, can be
      induced to occur in some organisms, including vertebrates, but has only been
      reported to occur naturally in interspecific hybrids of the Sicilian stick
      insect. Androgenesis has not been described previously in Drosophila. We now
      report the recovery of androgenetic offspring from Drosophila melanogaster
      females mutant for a gene that affects an oocyte- and embryo-specific alpha
      tubulin. The androgenetic exceptions are X,X diploid females that develop from
      haploid embryos and express paternal markers on all 4 chromosomes. The
      exceptional females arise by fusion of haploid cleavage nuclei or failure of
      newly replicated haploid chromosomes to segregate, rather than fusion of two
      inseminating sperm. The frequency of androgenetic offspring is greatly enhanced
      by a partial loss-of-function mutant of the NCD (nonclaret disjunctional)
      microtubule motor protein, suggesting that wild-type NCD functions is pronuclear
      fusion. Diploidization of haploid paternal chromosome complements results in
      complete genetic homozygosity, which could facilitate studies of gene variation
      and mutational load in populations.

PMID- 8524869
TI  - Human immunodeficiency virus 1 envelope-initiated G2-phase programmed cell death.
AB  - Despite intensive investigation, no clearly defined mechanism explaining human
      immunodeficiency virus (HIV)-induced cell killing has emerged. HIV-1 infection is
      initiated through a high-affinity interaction between the HIV-1 external envelope
      glycoprotein (gp120) and the CD4 receptor on T cells. Cell killing is a later
      event intimately linked by in vitro genetic analyses with the fusogenic
      properties of the HIV envelope glycoprotein gp120 and transmembrane glycoprotein
      gp41. In this report, we describe aberrancies in cell cycle regulatory proteins
      initiated by cell-cell contact between T cells expressing HIV-1 envelope
      glycoproteins and other T cells expressing CD4 receptors. Cells rapidly
      accumulate cyclin B protein and tyrosine-hyperphosphorylated p34cdc2 (cdk1)
      kinase, indicative of cell cycle arrest at G2 phase. Moreover, these cells
      continue to synthesize cyclin B protein, enlarge and display an abnormal
      ballooned morphology, and disappear from the cultures in a pattern previously
      described for cytotoxicity induced by DNA synthesis (S phase) inhibitors. Similar
      changes are observed in peripheral blood mononuclear cells infected in vitro with
      pathogenic primary isolates of HIV-1.

PMID- 8524870
TI  - A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis.
AB  - Fas, a member of the tumor necrosis factor receptor family, can induce apoptosis
      when activated by Fas ligand binding or anti-Fas antibody crosslinking. Genetic
      studies have shown that a defect in Fas-mediated apoptosis resulted in abnormal
      development and function of the immune system in mice. A point mutation in the
      cytoplasmic domain of Fas (a single base change from T to A at base 786),
      replacing isoleucine with asparagine, abolishes the signal transducing property
      of Fas. Mice homozygous for this mutant allele (lprcg/lprcg mice) develop
      lymphadenopathy and a lupus-like autoimmune disease. Little is known about the
      mechanism of signal transduction in Fas-mediated apoptosis. In this study, we
      used the two-hybrid screen in yeast to isolate a Fas-associated protein factor,
      FAF1, which specifically interacts with the cytoplasmic domain of wild-type Fas
      but not the lprcg-mutated Fas protein. This interaction occurs not only in yeast
      but also in mammalian cells. When transiently expressed in L cells, FAF1
      potentiated Fas-induced apoptosis. A search of available DNA and protein sequence
      data banks did not reveal significant homology between FAF1 and known proteins.
      Therefore, FAF1 is an unusual protein that binds to the wild type but not the
      inactive point mutant of Fas. FAF1 potentiates Fas-induced cell killing and is a
      candidate signal transducing molecule in the regulation of apoptosis.

PMID- 8524871
TI  - Localization, trafficking, and temperature-dependence of the Aequorea green
      fluorescent protein in cultured vertebrate cells.
AB  - The localization, trafficking, and fluorescence of Aequorea green fluorescent
      protein (GFP) in cultured vertebrate cells transiently transfected with GFP cDNA
      were studied. Fluorescence of GFP in UV light was found to be strongest when
      cells were incubated at 30 degrees C but was barely visible at an incubation
      temperature of 37 degrees C. COS-1 cells, primary chicken embryonic retina cells,
      and carp epithelial cells were fluorescently labeled under these conditions. GFP
      was distributed uniformly throughout the cytoplasm and nucleus independent of
      cell type examined. When GFP was fused to PML protooncogene product, fluorescence
      was detected in a unique nuclear organelle pattern indistinguishable from that of
      PML protein, showing the potential use of GFP as a fluorescent tag. To analyze
      both function and intracellular trafficking of proteins fused to GFP, a GFP-human
      glucocorticoid receptor fusion construct was prepared. The GFP-human
      glucocorticoid receptor efficiently transactivated the mouse mammary tumor virus
      promoter in response to dexamethasone at 30 degrees C but not at 37 degrees C,
      indicating that temperature is important, even for function of the GFP fusion
      protein. The dexamethasone-induced translocation of GFP-human glucocorticoid
      receptor from cytoplasm to nucleus was complete within 15 min; the translocation
      could be monitored in a single living cell in real time.

PMID- 8524872
TI  - Investigation of the prebiotic synthesis of amino acids and RNA bases from CO2
      using FeS/H2S as a reducing agent.
AB  - An autotrophic theory of the origin of metabolism and life has been proposed in
      which carbon dioxide is reduced by ferrous sulfide and hydrogen sulfide by means
      of a reversed citric acid cycle, leading to the production of amino acids.
      Similar processes have been proposed for purine synthesis. Ferrous sulfide is a
      strong reducing agent in the presence of hydrogen sulfide and can produce
      hydrogen as well as reduce alkenes, alkynes, and thiols to saturated hydrocarbons
      and reduce ketones to thiols. However, the reduction of carbon dioxide has not
      been demonstrated. We show here that no amino acids, purines, or pyrimidines are
      produced from carbon dioxide with the ferrous sulfide and hydrogen sulfide
      system. Furthermore, this system does not produce amino acids from carboxylic
      acids by reductive amination and carboxylation. Thus, the proposed autotrophic
      theory, using carbon dioxide, ferrous sulfide, and hydrogen sulfide, lacks the
      robustness needed to be a geological process and is, therefore, unlikely to have
      played a role in the origin of metabolism or the origin of life.

PMID- 8524873
TI  - Expression studies of catalytic antibodies.
AB  - We have examined the positive influence of human constant regions on the folding
      and bacterial expression of active soluble mouse immunoglobulin variable domains
      derived from a number of catalytic antibodies. Expression yields of eight
      hybridoma- and myeloma-derived chimeric Fab fragments are compared in both shake
      flasks and high density fermentations. In addition the usefulness of this system
      for the generation of in vivo expression libraries is examined by constructing
      and expressing combinations of heavy and light chain variable regions that were
      not selected as a pair during an immune response. A mutagenesis study of one of
      the recombinant catalytic Fab fragments reveals that single amino acid
      substitutions can have dramatic effects on the expression yield. This system
      should be generally applicable to the production of Fab fragments of catalytic
      and other hybridoma-derived antibodies for crystallographic and structure
      function studies.

PMID- 8524874
TI  - GAIP, a protein that specifically interacts with the trimeric G protein G alpha
      i3, is a member of a protein family with a highly conserved core domain.
AB  - Using the yeast two-hybrid system we have identified a human protein, GAIP (G
      Alpha Interacting Protein), that specifically interacts with the heterotrimeric
      GTP-binding protein G alpha i3. Interaction was verified by specific binding of
      in vitro-translated G alpha i3 with a GAIP-glutathione S-transferase fusion
      protein. GAIP is a small protein (217 amino acids, 24 kDa) that contains two
      potential phosphorylation sites for protein kinase C and seven for casein kinase
      2. GAIP shows high homology to two previously identified human proteins, GOS8 and
      1R20, two Caenorhabditis elegans proteins, CO5B5.7 and C29H12.3, and the FLBA
      gene product in Aspergillus nidulans--all of unknown function. Significant
      homology was also found to the SST2 gene product in Saccharomyces cerevisiae that
      is known to interact with a yeast G alpha subunit (Gpa1). A highly conserved core
      domain of 125 amino acids characterizes this family of proteins. Analysis of
      deletion mutants demonstrated that the core domain is the site of GAIP's
      interaction with G alpha i3. GAIP is likely to be an early inducible
      phosphoprotein, as its cDNA contains the TTTTGT sequence characteristic of early
      response genes in its 3'-untranslated region. By Northern analysis GAIP's 1.6-kb
      mRNA is most abundant in lung, heart, placenta, and liver and is very low in
      brain, skeletal muscle, pancreas, and kidney. GAIP appears to interact
      exclusively with G alpha i3, as it did not interact with G alpha i2 and G alpha
      q. The fact that GAIP and Sst2 interact with G alpha subunits and share a common
      domain suggests that other members of the GAIP family also interact with G alpha
      subunits through the 125-amino-acid core domain.

PMID- 8524875
TI  - Sequence similarity analysis of Escherichia coli proteins: functional and
      evolutionary implications.
AB  - A computer analysis of 2328 protein sequences comprising about 60% of the
      Escherichia coli gene products was performed using methods for database screening
      with individual sequences and alignment blocks. A high fraction of E. coli
      proteins--86%--shows significant sequence similarity to other proteins in current
      databases; about 70% show conservation at least at the level of distantly related
      bacteria, and about 40% contain ancient conserved regions (ACRs) shared with
      eukaryotic or Archaeal proteins. For > 90% of the E. coli proteins, either
      functional information or sequence similarity, or both, are available. Forty-six
      percent of the E. coli proteins belong to 299 clusters of paralogs (intraspecies
      homologs) defined on the basis of pairwise similarity. Another 10% could be
      included in 70 superclusters using motif detection methods. The majority of the
      clusters contain only two to four members. In contrast, nearly 25% of all E. coli
      proteins belong to the four largest superclusters--namely, permeases, ATPases and
      GTPases with the conserved "Walker-type" motif, helix-turn-helix regulatory
      proteins, and NAD(FAD)-binding proteins. We conclude that bacterial protein
      sequences generally are highly conserved in evolution, with about 50% of all ACR
      containing protein families represented among the E. coli gene products. With the
      current sequence databases and methods of their screening, computer analysis
      yields useful information on the functions and evolutionary relationships of the
      vast majority of genes in a bacterial genome. Sequence similarity with E. coli
      proteins allows the prediction of functions for a number of important eukaryotic
      genes, including several whose products are implicated in human diseases.

PMID- 8524876
TI  - Cytochrome P450 1A1 promoter as a genetic switch for the regulatable and
      physiological expression of a plasma protein in transgenic mice.
AB  - Transgenic and gene knockout techniques allow for in vivo study of the
      consequences of adding or subtracting specific genes. However, in some instances,
      such as the study of lethal mutations or of the physiological consequences of
      changing gene expression, turning on and off an introduced gene at will would be
      advantageous. We have used cytochrome p450 1A1 promoter to drive expression of
      the human apolipoprotein E (apoE) gene in transgenic mice. In six independent
      lines, robust expression of the transgene depended upon injection of the inducer
      beta-naphthoflavone, whereas the seventh line had high basal expression that was
      augmented further by the inducer. The low level of basal expression in an inducer
      dependent line was confirmed upon breeding the transgene onto the
      hypercholesterolemic apoE-deficient background. In the basal state transgene
      expression was physiologically insignificant, as these mice were as
      hypercholesterolemic as their nontransgenic apoE-deficient littermates. When
      injected with the inducer, plasma cholesterol levels of the transgenic mice
      decreased dramatically as apoE expression was induced to yield greater than
      physiological levels in plasma. The inducer could pass transplacentally from an
      injected mother to her fetuses with concomitant induction of fetal transgene
      mRNA. Inducer could also pass via breast milk from an injected mother to her
      suckling neonatal pups, giving rise to the induction of human apoE in neonate
      plasma. These finding suggest a strategy to temporarily ameliorate genetic
      deficiencies that would otherwise lead to fetal or neonatal lethality.

PMID- 8524877
TI  - Defective IgE production by SJL mice is linked to the absence of CD4+, NK1.1+ T
      cells that promptly produce interleukin 4.
AB  - SJL mice produce little or no IgE in response to polyclonal stimulation with anti
      IgD antibody and fail to express interleukin 4 (IL-4) mRNA in the spleen 5 days
      after injection of anti-IgD, in contrast to other mouse strains that produce
      substantial amounts of IgE and IL-4. Because IL-4 is critical in IgE production,
      the possibility that SJL mice are poor IgE producers because their naive T cells
      fail to differentiate into IL-4 producers must be seriously considered. IL-4
      itself is the principal factor determining that naive T cells develop into IL-4
      producers. A major source of IL-4 for such differentiation is a population of CD1
      specific CD4+ T cells that express NK1.1. These cells produce IL-4 within 90 min
      of anti-CD3 injection. T cells from SJL mice fail to produce IL-4 in response to
      injection of anti-CD3. Similarly, SJL T cells and CD4+ thymocytes do not produce
      IL-4 in response to acute in vitro stimulation. SJL T cells show a marked
      deficiency in CD4+ cells that express the surface receptors associated with the
      NK1.1+ T-cell phenotype. This result indicates that the SJL defect in IgE and IL
      4 production is associated with, and may be due to, the absence of the CD4+,
      NK1.1+ T-cell population.

PMID- 8524878
TI  - Structural basis for major histocompatibility complex (MHC)-linked susceptibility
      to autoimmunity: charged residues of a single MHC binding pocket confer selective
      presentation of self-peptides in pemphigus vulgaris.
AB  - Human T-cell-mediated autoimmune diseases are genetically linked to particular
      alleles of MHC class II genes. Susceptibility to pemphigus vulgaris (PV), an
      autoimmune disease of the skin, is linked to a rare subtype of HLA-DR4
      (DRB1*0402, 1 of 22 known DR4 subtypes). The PV-linked DR4 subtype differs from a
      rheumatoid arthritis-associated DR4 subtype (DRB1*0404) only at three residues
      (DR beta 67, 70, and 71). The disease is caused by autoantibodies against
      desmoglein 3 (DG), and T cells are thought to trigger the autoantibody production
      against this keratinocyte adhesion molecule. Based on the DRB1*0402 binding
      motif, seven candidate peptides of the DG autoantigen were identified. T cells
      from four PV patients with active disease responded to one of these DG peptides
      (residues 190-204); two patients also responded to DG-(206-220). T-cell clones
      specific for DG-(190-204) secreted high levels of interleukins 4 and 10,
      indicating that they may be important in triggering the production of DG-specific
      autoantibodies. The DG-(190-204) peptide was presented by the disease-linked
      DRB1*0402 molecule but not by other DR4 subtypes. Site-directed mutagenesis of
      DRB1*0402 demonstrated that selective presentation of DG-(190-204), which carries
      a positive charge at the P4 position, was due to the negatively charged residues
      of the P4 pocket (DR beta 70 and 71). DR beta 71 has a negative charge in
      DRB1*0402 but a positive charge in other DR4 subtypes, including the DR4 subtypes
      linked to rheumatoid arthritis. The charge of the P4 pocket in the DR4 peptide
      binding site therefore appears to be a critical determinant of MHC-linked
      susceptibility to PV and rheumatoid arthritis.

PMID- 8524880
TI  - The Nutrition Society 1994 Silver Medal Lecture. Pregnancy, parturition and
      neonatal development: interactions between nutrition and thyroid hormones.

PMID- 8524879
TI  - Production of avian leukosis virus particles in mammalian cells can be mediated
      by the interaction of the human immunodeficiency virus protein Rev and the Rev
      responsive element.
AB  - In human immunodeficiency virus type 1-infected cells, the efficient expression
      of viral proteins from unspliced and singly spliced RNAs is dependent on two
      factors: the presence in the cell of the viral protein Rev and the presence in
      the viral RNA of the Rev-responsive element (RRE). We show here that the HIV-1
      Rev/RRE system can increase the expression of avian leukosis virus (ALV)
      structural proteins in mammalian cells (D-17 canine osteosarcoma) and promote the
      release of mature ALV virions from these cells. In this system, the Rev/RRE
      interaction appears to facilitate the export of full-length unspliced ALV RNA
      from the nucleus to the cytoplasm, allowing increased production of the ALV
      structural proteins. Gag protein is produced in the cytoplasm of the ALV
      transfected cells even in the absence of a Rev/RRE interaction. However, a
      functional Rev/RRE interaction increases the amount of Gag present
      intracellularly and, more strikingly, results in the release of mature ALV
      particles into the supernatant. RCAS virus containing an RRE is replication
      competent in chicken embryo fibroblasts; however, we have been unable to
      determine whether the particles produced in D-17 cells are as infectious as the
      particles produced in chicken embryo fibroblasts.

PMID- 8524881
TI  - Nutritional influences on pancreatic development and potential links with non
      insulin-dependent diabetes.

PMID- 8524882
TI  - Nutrition in overseas aid: the investors' perspective.

PMID- 8524883
TI  - Priorities for nutrition interventions in reproductive health: a bilateral agency
      perspective.

PMID- 8524884
TI  - Investing in nutrition at the national level: an African perspective.

PMID- 8524885
TI  - Maternal nutrition and the regulation of milk synthesis.

PMID- 8524886
TI  - Evolutionary and environmental influences on human lactation.

PMID- 8524887
TI  - Breast-feeding: matching supply with demand in human lactation.

PMID- 8524888
TI  - The relationship between breast-feeding and infant health and development.

PMID- 8524889
TI  - How food preferences are learned: laboratory animal models.

PMID- 8524890
TI  - Food preferences in farm animals: why don't they always choose wisely?

PMID- 8524891
TI  - An effective procedure for changing food preferences in 5-7-year-old children.

PMID- 8524892
TI  - Understanding fat preference and consumption: applications of behavioural
      sciences to a nutritional problem.

PMID- 8524893
TI  - Iron-zinc and calcium-Fe interactions in relation to Zn and Fe absorption.

PMID- 8524894
TI  - Vitamin E and selenium: contrasting and interacting nutritional determinants of
      host resistance to parasitic and viral infections.

PMID- 8524895
TI  - Copper and zinc metabolism in health and disease: speciation and interactions.

PMID- 8524896
TI  - Interdependence of vitamin A and iron: an important association for programmes of
      anaemia control.

PMID- 8524897
TI  - Riboflavin-iron interactions with particular emphasis on the gastrointestinal
      tract.

PMID- 8524898
TI  - Intestinal oligopeptide transport.

PMID- 8524899
TI  - Regulation of gut glutamine metabolism: role of hormones and cytokines.

PMID- 8524900
TI  - Salvage of urea-nitrogen and protein requirements.

PMID- 8524901
TI  - Metabolic implications of ammonia production in the ruminant.

PMID- 8524902
TI  - Nutrition information and support for overseas members.

PMID- 8524903
TI  - Review of Macronutrient Metabolism Group workshop.

PMID- 8524904
TI  - The Sir David Cuthbertson Medal Lecture. Enteral-feeding-related diarrhoea:
      proposed causes and possible solutions.
AB  - So to summarize the key points: 1. concomitant antibiotic therapy, infected diets
      and possibly hypoalbuminaemia can lead to enteral-feeding-related diarrhoea; 2.
      the small intestinal responses to both intragastric and intraduodenal enteral
      feeding are normal and predictable; 3. there is an ascending colonic secretion
      during enteral feeding which is more profound during intragastric feeding; 4. the
      suppression of distal colonic motor activity occurs only during high-load feeding
      and is probably a secondary phenomenon to the hormonal and secretory responses;
      5. peptide YY appears to be intrinsically bound up with the causation of the
      secretory effect; 6. the secretory effect is abolished by intracaecal SCFA.

PMID- 8524905
TI  - The insulin-like growth factors in critical illness: pathophysiology and
      therapeutic potential.

PMID- 8524906
TI  - Outcrossing rates and correlated matings in a predominantly selfing freshwater
      snail.
AB  - We estimated outcrossing rates and correlated matings in a natural population of
      the hermaphroditic freshwater snail Ancylus fluviatilis, using progeny arrays and
      polymorphic allozyme markers. This design circumvents drawbacks of earlier
      studies, and yields maximum likelihood estimates of outcrossing rates at both the
      individual and population level. Adult snails were sampled during the spring
      breeding period, allowing for prior copulations and sperm transfer under natural
      conditions. Once in the laboratory, they were kept isolated for 21 days and laid
      egg capsules, and emerging hatchlings from 42 families were scored for five
      polymorphic loci. 87 of 848 offspring exhibited non-maternal alleles,
      representing a minimum population-level outcrossing of 10.3%. Maximum likelihood
      estimates are in the range 13-15%. Importantly, there is significant among-family
      heterogeneity, as only 16 of 42 families are estimated to have outcrossed, in
      accord with high estimates of correlated selfing within progeny arrays. Moreover,
      the high proportion of full sibs among outcrossed sibs suggests a limited extent
      of multiple paternity. Our data reveal important heterogeneity in the mating
      system of an animal hermaphrodite, and indicate the potential for evolutionary
      change in the breeding system.

PMID- 8524907
TI  - A geographic gradient in small rodent density fluctuations: a statistical
      modelling approach.
AB  - The patterns of density dependence in Fennoscandian rodents are investigated
      statistically using a linear autoregressive scheme. Nineteen time series of
      microtine abundances along a latitudinal gradient in Fennoscandia from 60 degrees
      N to 69 degrees N are analysed. We provide statistical evidence that there exists
      a latitudinal gradient in density dependence in Fennoscandian microtines.
      Southern populations experience significantly stronger direct density dependence
      than northern populations. Delayed density dependence was significantly negative
      throughout the region and appeared constant across the latitudinal gradient. The
      populations consistently exhibit dynamics of second order throughout the region.
      Together, the clinal direct density dependence and constant delayed density
      dependence give rise to a cline in cycle period from 3 to 4.5 years. The
      statistical results are compared to assumptions and predictions made in previous
      studies on the geographic gradient in the population dynamics of these rodents.
      The results are in agreement with the predictions of the 'generalist predator
      hypothesis'.

PMID- 8524908
TI  - Sexual conflict: males with highest mating success convey the lowest
      fertilization benefits to females.
AB  - In natural populations of a coral reef fish (the bluehead wrasse, Thalassoma
      bifasciatum), males with the highest daily mating success produce the fewest
      sperm per mating, and this is reflected in significantly lower fertilization
      rates. The average amount released by males in pair-mating was 3.3 x 10(6)
      spermatozoa, resulting in a fertilization rate of 96%. Sperm released per spawn
      declined with increasing mating success, so that females mating with the most
      successful males had less than 93% of their eggs fertilized. It is unlikely that
      high mating-success males are physiologically incapable of increasing sperm
      production, because younger males with different mating strategies have
      absolutely larger testes and higher daily sperm output. Feeding experiments
      suggest that high-success males are diverting energy from gamete production to
      other fitness-enhancing activities such as mate guarding. Females incur the cost
      of low sperm release by having fewer of their eggs fertilized. There are no
      obvious compensatory benefits to females from mating with high-success males.

PMID- 8524909
TI  - Cell-specific expression of the alpha 9 n-ACh receptor subunit in auditory hair
      cells revealed by single-cell RT-PCR.
AB  - Single-cell reverse transcription polymerase chain reaction was carried out in
      three different cell types from the organ of Corti of the four-day old rat. For
      this purpose, pieces of the organ of Corti were mounted under a differential
      interference contrast video microscope. Two different mounting configurations
      were used to allow imaging of cells from two almost orthogonal angles. This
      method afforded unequivocal recognition of various cell types in the vital
      tissue, and extraction of nucleus and cytoplasm of specified individual cells
      with a patch pipette. Messenger RNA encoding the alpha 9 acetylcholine (ACh)
      receptor subunit was detected and sequenced from individual outer hair cells and
      inner hair cells, but was not found in Deiters' cells. The identical Deiters'
      cells were positive for a P2x receptor subunit. This indicates cell-specific
      expression of the alpha 9 subunit in inner hair cells and outer hair cells and
      supports the hypothesis that this subunit contributes to calcium (Ca2+) permeable
      ionotropic ACh receptors (ACh-R). ACh-dependent Ca2+ concentration increase has
      been observed in both outer hair cells and inner hair cells.

PMID- 8524910
TI  - Life history plasticity in chimaeras of the colonial ascidian Botryllus
      schlosseri.
AB  - Colonies of the ascidian Botryllus schlosseri may fuse with kin to form chimaeras
      which vary their life histories depending on environmental conditions. We placed
      chimaeric colonies of this species in Monterey Bay, California, U.S.A., where
      they received planktonic food continuously. In the field, chimaeras grew rapidly,
      attained large sizes, and produced many eggs. They formed compact disc-shaped
      colonies in which genotypic composition remained stable throughout their
      lifespan. In most cases, genotypic partners in field chimaeras senesced and died
      synchronously. We also cultured genetically identical replicates of the same
      chimaeras under laboratory conditions, where they were fed once daily. In the
      laboratory environment, chimaeras grew slowly, shrank, and fragmented. Most
      genotypes in chimaeric colonies produced significantly fewer zooids and eggs in
      the laboratory than they did in the field. Somatic cell parasitism, in the form
      of resorption of tissues of one genotype by the other, occurred mainly in the
      laboratory environment, and not in the field. The phenomenon of resorption may
      thus be a dispensible strategy of fused genotypes depending on environmental
      conditions. Genotypes in field chimaeras may grow and reproduce rapidly because
      of the non-limiting food resources available. These data demonstrate that
      chimaeras of B. schlosseri have extremely plastic life histories, and employ
      different strategies depending on the environment.

PMID- 8524911
TI  - The relative fracture strengths of the inner and outer surfaces of the eggshell
      of the domestic fowl.
AB  - A method is described for comparing the strength of the material near the inner
      and outer surfaces of the eggshell of the domestic fowl. Half eggs with blunt
      poles, obtained by cutting the egg around the equator, were subjected to
      concentric loading through neoprene O-rings, respectively 7 mm and 15.5 mm
      diameter. A finite element solution for the stress distribution showed that the
      point of maximum tensile stress lay on the line of the smaller ring. For downward
      loading on the smaller ring, the maximum stress occurred on the inner surface of
      the shell. For upward loading it moved to the outer surface. Upward loading gave
      a value for the average fracture stress of the outer surface of the shell (27.3
      Nmm-2). For downward loading fracture occurred on the outer surface at the larger
      ring before the fracture stress was reached on the inner surface. This
      measurement gave a lower bound to the average fracture stress of the inner
      surface (30.4 Nmm-2). The fracture stress of the inner surface was measured using
      concentric loading along the axis of the whole egg. The average fracture stress
      was 36.7 Nmm-2 so the inner surface is 34% stronger than the outer surface.

PMID- 8524912
TI  - Determination of NMDA NR1 subunit copy number in recombinant NMDA receptors.
AB  - Co-expression of wild-type and mutated NMDA NR1 (N598R) subunits in Xenopus
      oocytes has been used to determine the stoichiometry of the NMDA receptor
      channel. When expressed together, wild-type NR2A and mutant NR1 (N598R) subunits
      produced channels with a main conductance of 2.6 pS and a sublevel of 1.2 pS.
      These conductances were clearly different from those obtained from wild-type NR1
      and wild-type NR2A channels which gave characteristic 50 pS events with a 40 pS
      sublevel. When wild-type and mutant NR1 subunits were co-expressed together with
      NR2A subunits a different channel type with a main conductance of 15.2 pS and a
      sublevel of 11.4 pS was obtained, as well as the 'all wild-type' and 'all mutant'
      channels described above. These results indicate that there are likely to be two
      copies of the NR1 subunit in each NMDA receptor complex.

PMID- 8524913
TI  - Handling-induced stress and mortalities in African wild dogs (Lycaon pictus).
AB  - Recently it was suggested that the handling of wild dogs (Lycaon pictus) by
      researchers in the Serengeti ecosystem created stress, resulting in the
      reactivation of latent rabies viruses in carrier animals. We present data from
      ongoing studies on free-ranging and captive wild dogs elsewhere in Africa which
      do not support this hypothesis. Cortisol profiles suggest that immobilization of
      wild dogs does not cause the chronic stress required for stress-reactivation of
      latent viruses. Furthermore, there is no evidence of handling-related mortalities
      in wild dogs: the survivorship of unhandled and handled free-ranging wild dogs
      did not differ and no captive animals died within a year of handling
      (immobilization and/or vaccination against rabies). We suggest that the
      mortalities observed in Tanzania were due to an outbreak of a disease which
      rabies vaccination was unable to prevent. Intensive monitoring and active
      management research programmes on wild dogs are essential as without these,
      critically endangered wild dog populations have little hope of survival.

PMID- 8524914
TI  - Local extinction in a small and declining population: wild dogs in the Serengeti.
AB  - Altered assumptions about how different ecological factors limit population
      numbers may lead to different conclusions about the causes of decline and
      ultimate extinction of a small population. Here, alternative hypotheses for the
      local disappearance of the Serengeti plains study population of African wild dogs
      (Lycaon pictus) are examined in light of observations of density dependence,
      deterministic decline and frequent rapid fluctuations in population number. After
      a population crash from 60 individuals in 1975 to 30 individuals in 1976, the
      Serengeti plains population fluctuated around a mean value of 22 individuals for
      16 years before local extinction occurred. Variation in population numbers was
      extreme, with inter-annual reductions in population size of at least 40%
      occurring three times. Several explanations are consistent with the observed
      trends in population size including outbreaks of various epizootics and
      competition with other predators. Monte Carlo simulation, with parameters set to
      reflect observed fluctuations, demonstrate that population extinction was likely
      from chance factors alone. In small and declining populations, for which precise
      data and controls are unavailable, determining the cause(s) of extinction usually
      will be impossible.

PMID- 8524915
TI  - Rabies and African wild dogs in Kenya.
AB  - Three packs of African wild dogs (Lycaon pictus) ranging to the north of the
      Masai Mara National Reserve in southwestern Kenya were monitored from 1988 to
      1990. During a six week period (August 2-September 14, 1989), 21 of 23 members of
      one of these packs died. Histological examination of two brain samples revealed
      eosinophilic intracytoplasmic inclusions (Negri bodies), supporting a diagnosis
      of rabies viral encephalitis. An additional brain sample tested positive for
      rabies with a fluorescent antibody test. Nucleotide sequence of the rabies viral
      N and G genes from isolates of four African wild dogs (including an individual
      from Tanzania) indicated that infection was with a viral variant common among
      domestic dogs in Kenya and Tanzania. A hypothesis linking African wild dog rabies
      deaths to researcher handling is evaluated and considered implausible.

PMID- 8524916
TI  - Population dynamics, intervention and survival in African wild dogs (Lycaon
      pictus).
AB  - The demography of Serengeti wild dog study packs and their extinction in 1991 was
      documented by Burrows et al. (1994). One explanation for pack loss compatible
      with demographic evidence was viral disease induced by stress caused by
      intervention (vaccination, immobilization and radio-collaring). Several studies
      claim to reject this hypothesis. However, cortisol levels measured in immobilized
      Lycaon, whose pathogen exposure is unknown, do not demonstrate that interventions
      in the Serengeti were benign. The analysis of survivorship in Lycaon in other
      ecosystems minimized the chance of demonstrating any effect of intervention and
      failed to consider vaccinations as intervention. There is now evidence that
      intervention significantly decreased survivorship of Masai Mara Lycaon. Further
      simulations of the likelihood of population extinction in Serengeti Lycaon,
      evidence of limited population variability and a small scaling factor in
      Serengeti Lycaon strengthen Burrows et al.'s conclusion that the extinction was
      unlikely to be due to chance alone. Although some studies claim that Lycaon
      conservation is doomed without intervention, to date vaccinations, blood sampling
      and radio-telemetry have contributed little to Lycaon conservation. All studies
      fail to disprove the Burrows hypothesis or provide convincing alternatives.

PMID- 8524917
TI  - Use of plasma desorption mass spectrometry in structural analysis of endotoxins:
      effects on lipid A of different acid treatments.

PMID- 8524918
TI  - The lipopolysaccharide of Legionella pneumophila serogroup 1 (strain Philadelphia
      1): chemical structure and biological significance.
AB  - The lipopolysaccharide (LPS, endotoxin) of Legionella pneumophila serogroup 1
      (Philadelphia 1) exhibits peculiar chemical features which may account for its
      importance as a bacterial virulence factor. The O-chain of this LPS constitutes a
      homopolymer of an unusual sugar, 5-acetamidino-7-acetamido-8-O-acetyl-3,5,7, 9
      tetradeoxy-D-glycero-L-galacto-nonulosonic acid (legionaminic acid) of which
      about 10-75 residues are present. Due to the lack of free hydroxyl groups, this
      homopolymer renders the cell surface highly hydrophobic and, therefore, supports
      adherence to the membrane of target cells including alveolar macrophages.
      Investigations of the serological specificity of the serogroup 1 LPS revealed a
      monoclonal antibody (mAb 3/1) which recognizes an epitope located in the
      environment of the 8-O-acetyl group of legionaminic acid. According to
      epidemiological studies, this determinant appears to be associated with L.
      pneumophila virulence. The outer core oligosaccharide of L. pneumophila LPS
      exhibits also hydrophobic properties due to the presence of N- and O-acetyl
      groups as well as 6-deoxy sugars. The inner core expresses both similarities and
      differences as compared to enterobacterial core oligosaccharides in containing
      Kdo but lacking heptose and phosphate groups. Lipid A possesses some unique
      structural features since its backbone consists of a bisphosphorylated beta
      GlcpN3N-(1-->6)-GlcpN3N disaccharide with only amide-linked acyl groups having 14
      22 carbon atoms. Long chain fatty acids [28:0(27-oxo) and 27:0-dioic] possessing
      the double length as enterobacterial acyl groups, may be responsible for the low
      endotoxicity of L. pneumophila lipid A.

PMID- 8524919
TI  - Cell wall antigens in Vibrio cholerae O139 Bengal, a causative agent of new
      epidemics.

PMID- 8524920
TI  - Increased substitution of phosphate groups in lipopolysaccharides and lipid A of
      polymyxin-resistant mutants of Salmonella typhimurium and Escherichia coli.

PMID- 8524921
TI  - Novel method for the purification and characterization of lipopolysaccharide from
      Escherichia coli D31m3.

PMID- 8524922
TI  - Immunochemical aspects of lipopolysaccharide of Vibrio cholerae O139 Bengal, a
      new epidemic strain for recent, fast-spreading cholera in the Indian
      subcontinent.

PMID- 8524923
TI  - Conformation and fluidity of endotoxins as determinants of biological activity.

PMID- 8524924
TI  - Physical state of biologically active lipopolysaccharide.

PMID- 8524925
TI  - Significance of translocation/endotoxin in the development of systemic sepsis
      following trauma and/or haemorrhage.

PMID- 8524926
TI  - The role of bacterial translocation on Kupffer cell immune function following
      hemorrhage.
AB  - Studies have shown that Kupffer cell and splenic macrophage, as well as
      peritoneal macrophage antigen presentation function, was significantly depressed
      following hemorrhage and remained so for at least 96 hours after resuscitation.
      Although macrophage antigen presentation was depressed, in all the cell
      populations studied, it was only the Kupffer cells which were upregulated to
      produce increased inflammatory cytokines. Furthermore, Kupffer cells from
      hemorrhaged animals exhibited enhanced, as opposed to reduced toxicity by
      peritoneal and splenic macrophages. This correlated well with increased cell
      associated TNF on Kupffer cells. as well as increased capacity of Kupffer cells
      to release inflammatory cytokines after hemorrhage. It, therefore, could be
      postulated that while the enhanced Kupffer cell cytotoxicity may be beneficial in
      the destruction of pathogens seen in the liver due to bacterial translocation,
      this same activity may also contribute directly or indirectly to hepatocellular
      dysfunction and injury which is seen following hemorrhagic shock. Nonetheless,
      the depression in various immune functions after hemorrhage and resuscitation was
      comparable in both endotoxin-tolerant and -intolerant mice. Thus, it is debatable
      whether the alterations in immune function seen after hemorrhage are primarily
      due to the release of endotoxin into the blood stream during and/or following the
      hemorrhagic insult. Although translocation and/or endotoxemia occurs following
      severe hemorrhage, endotoxin may not be the sole or primary agent responsible for
      the induction of immunodepression after hemorrhage. The depressed Kupffer cell
      functions and increased inflammatory cytokine release by these cells can be
      significantly improved by post-treatment of animals with chloroquine, ibuprofen,
      diltiazem or ATP-MgCl2. Thus, these agents offer new therapeutic modalities in
      restoring the depressed Kupffer cell immune functions and in the treatment of
      generalized immunosuppression, as well as for decreasing the susceptibility to
      sepsis which is observed following severe blood loss.

PMID- 8524927
TI  - Bacteremia and compartmentalization of LPS in meningococcal disease.

PMID- 8524928
TI  - Quantitative variations in beta-lactam antibiotic released endotoxin from
      Pseudomonas aeruginosa: in-vivo relevance.

PMID- 8524929
TI  - The structure and biosynthesis of Rhizobium leguminosarum lipid A.

PMID- 8524930
TI  - Endotoxin (Salmonella abortus equi) in cancer patients. Clinical and
      immunological findings.
AB  - 1. LPS phase I trial revealed MTD I of 1.0 ng/kg body weight and MTD II of 5.0
      ng/kg body weight, the latter given together with ibuprofen (1,600 mg). 2. LPS
      phase II trial, using 4,0 ng/kg body weight plus ibuprofen in a biweekly schedule
      didn't show any response in patients with non-small cell lung cancer but 1 CR and
      2 PR (13% response rate) in colorectal cancer patients. 3. The LPS tolerance is
      specific for each cytokine and mediator in regard to the kinetic and degree of
      its development. INF-gamma prevents the tolerance development to several
      cytokines with the exception of IL-8. 4. No tolerance was found in cell adhesion,
      phospholipase A2, and soluble TNF receptor I and II. Priming of ex vivo cytokine
      production of cytokines was found in mononuclear cells. 5. Synthetic LPS partial
      structure SDZ-MRL 953 (I) induces a cytokine pattern, which is profoundedly
      different from that of LPS, (II) with an inverse TNF to G-CSF relation, (III) is
      (without any ibuprofen treatment) remarkably low toxic, (IV) and downregulates
      the TNF-response to LPS markedly.

PMID- 8524931
TI  - Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure
      and a prognostic indicator: a review.

PMID- 8524932
TI  - A rapid test for endotoxin in whole blood.
AB  - A rapid whole blood agglutination test has been developed for the detection of
      endotoxin. The test reagent consists of polymyxin B (PmB) conjugated to the Fab
      fragment of the anti-glycophorin antibody 1C3/86. After addition of reagent to
      whole blood, red cell agglutination occurs within two minutes in samples from
      endotoxaemic patients or with the addition of either whole Gram negative
      bacteria, supernatants from Gram negative bacterial cultures or purified
      endotoxin. In clinical samples there was a strong correlation (r = 0.83) between
      the strength of agglutination and the level of endotoxin measured by the Limulus
      amaebolysate test (LAL). The prospect of a rapid and accurate test for endotoxin
      may enable better clinical management of Gram negative sepsis.

PMID- 8524933
TI  - Lipopolysaccharide (LPS) binding protein catalyzes binding of LPS to
      lipoproteins.
AB  - Lipoproteins isolated from normal human plasma can bind and neutralize bacterial
      lipopolysaccharide (LPS) and may represent an important mechanism in host defense
      against gram-negative septic shock. We sought to define the components of high
      density lipoproteins (HDL) that are required for neutralization of LPS. To
      accomplish this we have studied the functional neutralization of LPS by native
      and reconstituted HDL using a rapid assay that measures the CD14-dependent
      activation of leukocyte integrins on human neutrophils. Reconstituted HDL
      particles (R-HDL), prepared from purified apolipoprotein A-I (apoA-I) combined
      with phospholipid and free cholesterol, were not sufficient to neutralize the
      biologic activity of LPS. However, addition of recombinant LPS binding protein
      (LBP), a protein known to transfer LPS to CD14 and enhance responses of cells to
      LPS, enabled prompt binding and neutralization of LPS by R-HDL. Thus, LBP appears
      capable of transferring LPS not only to CD14 but also to lipoprotein particles.
      These results suggest that in addition to its ability to transfer LPS to CD14,
      LBP may also transfer LPS to lipoproteins. Additional studies demonstrated that
      LBP copurifies with native apoA-I containing lipoprotein (Lp(A-I)) particles.
      Since LBP appears to be physically associated with lipoproteins in plasma, it is
      positioned to play an important role in the neutralization of LPS.

PMID- 8524934
TI  - Mechanisms of transcriptional activation of lipopolysaccharide binding protein
      (LBP).
AB  - The Lipopolysaccharide Binding Protein (LBP) is of high importance for endotoxin
      recognition, presentation and subsequent cytokine induction in immune cells. LBP,
      which is a member of a growing family of structurally and functionally related
      proteins, is synthesized in hepatocytes and secreted into the blood stream
      constitutively. During the acute phase response, however, LBP levels rise
      substantially and here the mechanisms of induction of LBP protein synthesis were
      reviewed. The induction of LBP in hepatocytes is due to transcriptional and
      posttranscriptional mechanisms as we have shown by nuclear run-on and RNA half
      life experiments. Cloning of the 5'-flanking region of the LBP gene, furthermore
      revealed a typical acute phase protein promoter. Reporter gene assays employing
      the luciferase gene and mutation variants of the LBP promoter revealed that
      integrity of a common acute phase promoter motif, named APRE/STAT-3 is essential
      for activation of the LBP promoter. Elucidation of the transcriptional activation
      mechanism could point the way to a therapeutically lowering of LBP levels in high
      risk patients for reducing their susceptibility to Gram-negative septic shock.

PMID- 8524935
TI  - Molecular genetics of polymyxin resistance in Salmonella typhimurium.
AB  - Resistance to Polymyxin and CAP are conferred by a point mutation, pmrA505, in
      position 81 that results in an Arg to His substitution in pmrA, a regulator
      protein. The protein, pmrB is expressed in the cell membrane. This is consistent
      with the hypothesis that it is a sensor/kinase protein. A newly discovered gene,
      pmrD, confers resistance to polymyxin B equal to that of pmrA505 when expressed
      on a multicopy plasmid, but such transformed strains are not resistant to CAP.
      Evidence is presented that pmrA505 can be expressed, but only suboptimally, in
      the absence of pmrD. However, there is an absolute requirement for pmrA+ in order
      for pmrD to express resistance to polymyxin B. It is therefore suggested that
      pmrD is regulated by the two component regulatory pair pmrAB.

PMID- 8524936
TI  - Stimulated human neutrophils release intact BPI without a concomitant change in
      expression on the cell surface.

PMID- 8524937
TI  - Structure and functions of endotoxin-binding peptides derived from CAP18.
AB  - CAP18 (cationic antimicrobial protein, 18kDa) is a 142 amino acid protein
      originally isolated from rabbit granulocytes using agglutination of LPS-coated
      erythrocytes as an assay. CAP-18 is composed of an N-terminal domain of unknown
      function (CAP181-105) and a C-terminal LPS-binding domain (CAP18106-142).
      Synthetic CAP18106-142 and CAP18106-137, a 32-amino acid peptide resulting from
      the truncation of 5 amino acids from the C-terminus of CAP18106-142, inhibited
      LPS-induced tissue factor generation, nitric oxide production and TNF release by
      macrophages. Mice treated with CAP18106-142 or CAP18106-137 were significantly
      protected from LPS lethality. Although CAP18106-142 and CAP18106-137 were highly
      active, other fragments of CAP18106-142, including CAP18110-142 with a truncated
      N-terminus, did not exhibit LPS-binding and LPS-neutralizing activities. Both
      peptides had broad anti-microbial activity against both Gram-negative bacteria
      such as Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae,
      Pseudomonas aeruginosa (IC50; 40-100 nM) and Gram-positive bacteria such as
      Staphylococcus aureus(Methicillin sensitive and resistant strains) and
      Streptococcus pneumoniae (IC50; 100-200nM). We cloned a CAP18 family protein from
      human granulocytes. The cloned cDNA encoded 140 amino acid residues. Human CAP18
      (CAP181-140) was highly homologous to that of rabbit. A 32- amino-acid C-terminal
      fragment (CAP18104-135) was shown to bind LPS, inhibit LPS-induced tissue factor
      generation by murine macrophages, and protect mice from LPS lethality. This
      peptide exhibited antimicrobial activity against both Gram-negative and Gram
      positive bacteria. We hypothesize that CAP18 and the derived peptides bind to LPS
      and alter the capacity of LPS to initiate disseminated intravascular coagulation.
      In this regard, CAP may act as host defense protein against infectious diseases,
      and have therapeutic potential for sepsis and endotoxin shock.

PMID- 8524938
TI  - Identification of the LPS-binding domain of an endotoxin neutralising protein,
      Limulus anti-LPS factor.

PMID- 8524939
TI  - Modalities of endotoxin binding to CD14.

PMID- 8524940
TI  - CD14-deficient mice are exquisitely insensitive to the effects of LPS.

PMID- 8524941
TI  - Molecular genetic manipulation of nonenteric bacterial pathogens to synthesise
      altered lipopolysaccharide molecules.

PMID- 8524942
TI  - Modulation of protein tyrosine phosphorylation in human cells by LPS and
      enzymatically deacylated LPS.
AB  - Previous studies have shown that the antagonism of LPS-induced responses by lipid
      A analogs and the induction of tolerance (adaptation) to LPS can occur without
      decreasing LPS binding to CD14. To learn more about these inhibitory mechanisms,
      we studied the effects of LPS and dLPS on an early response in the LPS signal
      pathway, protein tyrosine phosphorylation. Using CD14-expressing THP-1 cells, we
      found that very low concentrations of LPS stimulated tyrosine phosphorylation of
      a 42 kDa protein (p42). dLPS did not stimulate detectable phosphorylation of a 42
      or any other cellular protein, but it inhibited the ability of LPS to induce this
      response. dLPS was a potent inhibitor when added to the cells at the same time as
      LPS, but not when added one or two minutes after LPS. Exposing cells to LPS for 3
      hours induced a state of tolerance (adaptation) in which the cells were
      refractory to restimulation of p42 phosphorylation by LPS, but not by other
      agonists. The duration of LPS-induced tolerance (8-16 hours) was much longer than
      the duration of the refractory state resulting from dLPS pre-treatment (under 2
      hours). Cellular binding and uptake of LPS were not significantly reduced by
      preexposing the cells to LPS or dLPS. The data indicate that the mechanisms of
      dLPS antagonism and LPS-induced tolerance occur distal to CD14 binding and
      proximal to p42 tyrosine phosphorylation.

PMID- 8524943
TI  - Site-directed mutagenesis of baboon CD14 to the human sequence allows for
      antibody recognition and enhanced LPS binding.

PMID- 8524944
TI  - Activation of endothelial cells by endotoxin: direct versus indirect pathways and
      the role of CD14.
AB  - Optimal activation of endothelial cells by nanomolar quantities of endotoxin
      (lipopolysaccharide, LPS) requires the presence of plasma or serum. We and others
      have demonstrated that soluble CD14 (sCD14) and LPS binding protein (LBP) were
      the key plasma proteins mediating endothelial cell responses to LPS. The role of
      LBP is to transfer LPS to sCD14 and newly formed LPS-sCD14 will in turn activate
      endothelial cells via an as yet unknown surface receptor. This plasma-dependent
      pathway of endothelial cells activation is referred as to the direct pathway.
      However, endothelial cells are in constant contact with whole blood and not only
      with plasma. In experiments where whole blood was substituted for plasma, we
      showed that endothelial cells became sensitive to picomolar, rather than
      nanomolar quantities of LPS. The fact that endothelial cell responses were
      amplified by the presence of whole blood prompted us to search for the
      responsible blood cell(s) and mediator(s) for this effect. Blood cell
      fractionation experiments, experiments with blood from PNH patients and the use
      of anti-CD14 antibodies pointed to the monocyte as the blood cell responsible for
      the amplification effect. Moreover, the blood effect could be entirely reproduced
      by cells from a CD14-expressing cell line, such as calcitriol-differentiated HL
      60 cells. Inhibitors to TNF and to IL-1 blocked LPS-induced activation of
      endothelial cells partially when added separately to whole blood, but abrogated
      endothelial cell responses when added together. Thus, the whole blood effect
      begins with LPS activation of monocytes via cell membrane CD14 and results in
      endothelial cell activation by the effects of TNF and IL-1. The monokine-mediated
      endothelial cell activation is referred as to the indirect pathway.

PMID- 8524945
TI  - Soluble CD14 in septic shock.

PMID- 8524946
TI  - Selective inhibition of the activity of inducible nitric oxide synthase in septic
      shock.

PMID- 8524947
TI  - Endotoxin versus bacteremia: a comparison focusing on clinical relevance.
AB  - All phenomena seen under ovine endotoxemia or bacteremia are typically observed
      in septic humans as well. The lethality (approximately 20%) in both sepsis models
      underlines the severity of the experimental sepsis in these models. As mentioned
      above, both models are ideal to objectify the effects of new therapeutic
      approaches for the treatment of sepsis, because they provide stable conditions.
      We tested the inhibition of nitric oxide synthase in both models: Nitric oxide is
      the main mediator of the vasodilation and the hyperdynamic circulation seen in
      sepsis. Since the restoration of the perfusion pressure is the major therapeutic
      goal to prevent further tissue damage (Chernow et al. 1990), the blockade of the
      nitric oxide synthase seems to be a logical approach for the treatment of
      hyperdynamic sepsis. Therefore, we tested the nitric oxide synthase inhibitor
      N(W)-nitro-L-arginine methyl ester (L-NAME) in the endotoxemic sheep model as
      well as in the bacteremic model. L-NAME reversed the hyperdynamic circulation of
      sepsis (Meyer et al.1992; Dehring et al.1993). The cardiac output was lowered
      back to baseline, and at the same time, the arterial pressure was elevated to
      baseline niveau, both resulting in a marked increase in systemic vascular
      resistance (figure 3). The pulmonary artery pressure showed only a slight
      increase, but due to the marked reduction in cardiac output the pulmonary
      vascular resistance increased significantly. The oxygen extraction was elevated
      to an extent, which prevented the oxygen consumption to fall, although the oxygen
      delivery dropped significantly because of the lowered cardiac output (figure 4).
      The intrapulmonary shunt was brought back to baseline (Meyer et al.1994a),
      allowing an improved pulmonary oxygen uptake. The renal function improved
      significantly after nitric oxide synthase inhibition in endotoxemia as well as in
      bacteremia (Hinder et al.1994; Lingnau et al.1994). Not only was the creatinine
      clearance elevated, but the urine output also increased, lowering the positive
      fluid balance. Another inhibitor of nitric oxide synthase N(W)-Mono-Methyl-L
      Arginine (L-NMMA) was recently tested in these models as well. This drug is now
      already in clinical trials. The fact that the effects of these nitric oxide
      synthase inhibitors in septic humans are similar to the effects in the described
      experimental sepsis models proves the clinical relevance of the endotoxemic and
      the bacterimic sheep model.

PMID- 8524948
TI  - Examination of the role of MAP kinase in the response of macrophages to
      lipopolysaccharide.
AB  - Although the mechanism by which macrophages and other mammalian cells recognize
      LPS is still only partially understood, there has been considerable recent
      progress in unraveling the mechanisms by which putative cell surface LPS
      receptors transmit information of ligand binding to the interior of the cell. In
      macrophages, LPS induces protein tyrosine phosphorylation of a handful of
      proteins. We have identified two of the more prominent phosphorylated proteins as
      p42 and p44 MAP kinases. In addition, we have examined the role of MAP kinases in
      the macrophage response to LPS by utilizing a regulatable form of Raf-1 to
      activate MAP kinases independently of LPS. These experiments suggest that MAP
      kinases participate in LPS signaling, but also demonstrate that activation of MAP
      kinases cannot account for all of the intracellular events triggered by LPS.
      Therefore LPS must activate other signaling events that contribute to NF-kappa B
      activation and TNF-alpha mRNA accumulation and protein secretion.

PMID- 8524949
TI  - Dissection of LPS-induced signaling pathways in murine macrophages using LPS
      analogs, LPS mimetics, and agents unrelated to LPS.
AB  - The model in Figure 3 summarizes the data presented above. Using the induction of
      the select panel of LPS-inducible genes and the phosphorylation on tyrosine of
      specific MAP kinases, we have been able to dissociate three signaling pathways
      shared by LPS and its analogs and mimetics: a pathway that leads to tyrosine
      phosphorylation, one that leads to the induction of a gene subset including TNF
      alpha, TNFR-2, and IL-1 beta, and a pathway that results in induction of IP-10,
      D3, and D8 gene expression. It is still unclear if macrophage activation by non
      LPS products occurs entirely through distinct yet redundant pathways or if other
      signaling receptors ultimately tie into the same intermediate pathways. This
      approach may identify particular stimuli as tools to induce specific pathways
      leading to select gene subsets and/or tyrosine kinase activation and, perhaps,
      identify a pathway deficient in C3H/HeJ macrophages.

PMID- 8524950
TI  - The production of TNF alpha and IL-8 in whole blood assays are differently
      regulated upon activation by LPS.

PMID- 8524951
TI  - Rational computer-aided design of ligands that bind endotoxin.

PMID- 8524952
TI  - Diversity in lipid A binding ligands: comparison of lipid A monoclonal antibodies
      with rBPI23.
AB  - 1. Mabs with a high affinity for free lipid A do not bind when it is covalently
      linked, i.e. in the form of LPS. 2. Lipid A-binding Mabs may be divided into
      three categories: I. Monoreactive Mabs that bind to the hydrophillic backbone of
      lipid A II. Polyreactive Kdo Mabs III. Polyreactive Mabs that bind by hydrophobic
      interactions 3. rBPI23 binds either free or covalently linked lipid A.

PMID- 8524953
TI  - Contribution of lipopolysaccharide binding protein (LBP) in endotoxemic shock in
      mice.

PMID- 8524954
TI  - Therapeutic strategies to block LPS interactions with its receptor.

PMID- 8524955
TI  - Recombinant soluble CD14 inhibits LPS-induced mortality in a murine model.

PMID- 8524956
TI  - Use of CD14 transfected cells to study LPS-antagonist action.

PMID- 8524957
TI  - Function of lipopolysaccharide in the invasion of Neisseria gonorrhoeae into
      human mucosal cells.
AB  - The variable incorporation of sialic acid into the LPS of Neisseria gonorrhoeae
      modulates the invasive behavior of this bacterium towards cultured human
      epithelial cells. Here we report that the inhibitory effect of LPS sialylation on
      the gonococcal entry into Chang epithelial cells and ME-180 endocervical cells
      (van Putten, EMBO J 12:4043-4051, 1993) is located early in the uptake pathway
      upstream of the invasion-associated recruitment of F-actin at the sites of
      bacterial entry, but beyond the level of bacterial adherence. Receptor
      equilibrium studies using purified radiolabelled opacity protein receptor
      demonstrated that LPS sialylation caused a 3-5 fold reduction in binding of the
      bacterial invasion-promoting opacity outer membrane protein to its receptor. In
      HEC-1B and PC-3 cells, LPS sialylation did only partially inhibit the bacterial
      entry process, suggesting the existence of a second uptake mechanism for
      gonococci in these cell lines. Experiments with non-sialylatable and truncated
      isogenic LPS variants, and with genetically defined LPS mutants demonstrated that
      the invasive phenotype of N. gonorrhoeae requires a minimum of an Rc (or Rd1)
      chemotype of LPS. Variation within the LPS outer core region did not influence
      the invasive properties of the bacteria as long as there was no attached sialic
      acid.

PMID- 8524958
TI  - Anti-endotoxin activity of a novel synthetic lipid A analog.
AB  - Lipid As from non-toxic bacteria such as Rhodobacter capsulatus and Rhodobacter
      sphaeroides have been shown to antagonize the immunostimulatory effects of lipid
      A and LPS from pathogenic bacteria. We have biologically characterized a series
      of synthetic LPS antagonists including the proposed structures of the lipid A and
      R. sphaeroides containing fatty acid side chains ester-linked to the disaccharide
      backbone, as well as an analog of R. capsulatus lipid A containing ether-linked
      alkyloxy side chains (E5531). In vitro assays utilizing LPS-stimulated human
      monocytes or whole blood demonstrated that low nanomolar concentrations of E5531
      inhibited cellular activation as indicated by decreased release of the cytokines
      TNF-a, and interleukins-1, 6, and 8. E5531 also inhibited LPS-induced release of
      cytokines and nitric oxide from murine macrophages. Synthetic antagonists at up
      to 100 microM were devoid of agonistic activity in murine and human in vitro
      systems. In vivo, E5531 blocked induction of TNF-a by LPS and reduced LPS-induced
      lethality in mice. These in vitro and in vivo results indicate that E5531 may
      have clinical therapeutic utility as an antagonist of endotoxin-mediated
      morbidity and mortality.

PMID- 8524959
TI  - Formation of a TNF synthesis inhibitor in endotoxin tolerance.

PMID- 8524960
TI  - Different regulation of TNF alpha and IL-1ra synthesis in LPS-tolerant human
      monocytes.

PMID- 8524961
TI  - Reorientation of macrophage mediator production in endotoxin tolerance.
AB  - During endotoxin shock macrophages produce arachidonic acid (AA) metabolites,
      nitric oxide (NO) and interleukin 6 (IL-6). In contrast, macrophages from
      endotoxin tolerant rats become hyporesponsive to LPS-induced AA metabolites
      production. However the role of NO and IL-6 during endotoxin tolerance is not
      known. Therefore, we evaluated the production of the AA metabolite 6-keto
      prostaglandin F1 alpha (6-keto-PGF1 alpha), IL-6 and NO (by nitrite measurement)
      by peritoneal macrophages from endotoxin tolerant rats. Since pertussis toxin
      (PT) sensitive guanine nucleotide binding regulatory (Gi) protein activity is
      altered during endotoxin tolerance, we also studied the effect of PT on the
      regulation of the above mediators synthesis. Endotoxin tolerance was induced in
      rats by intraperitoneal injection of a sublethal dose of Salmonella enteritidis
      lipopolysaccharide (LPS, 100 micrograms/kg ip). Peritoneal macrophages were
      harvested 24 hours after LPS injection and stimulated in vitro with LPS (50
      micrograms/ml) for determination of NO activity by nitrite, 6-keto-PGF1 alpha and
      IL-6 production. In macrophages collected from vehicle-pretreated rats (control)
      LPS stimulates all three mediators. In vivo pretreatment with LPS induced a
      desensitization of macrophages to LPS-induced 6-keto-PGF1 alpha production
      compared to control macrophages (p < 0.001). LPS-stimulated IL-6 synthesis was
      also partially, but not completely, reduced in tolerant macrophages (p < 0.001
      versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524962
TI  - Mechanisms to induce tolerance by synthetic monosaccharide lipid A analogues
      against LPS lethality in mice.

PMID- 8524963
TI  - SDZ MRL 953, a lipid A analog as selective cytokine inducer.

PMID- 8524964
TI  - Monophosphoryl lipid A as a prophylactic for sepsis and septic shock.
AB  - The ability of monophosphoryl lipid A (MLA) to provide prophylactic protection
      against septic shock was evaluated in a mouse model of induced endotoxin
      hypersensitivity. Treatments of hypersensitized animals with low doses of MLA
      attenuated endotoxin lethality and endotoxin-mediated liver damage. These effects
      were related to the ability of MLA to suppress accumulation of TNF-alpha and IFN
      gamma in the bloodstream of animals. MLA treatments had only a modest effect in
      suppressing the accumulation of nitrate in the bloodstream. This implied that MLA
      did not suppress induction of macrophage and hepatocyte nitric oxide synthetases
      that contribute to antimicrobial defense and protect against endotoxin-mediated
      liver damage. The MLA treatments did not appear to compromise inflammatory
      defenses against local infection since locally recruited leukocytes remained
      responsive to endotoxin after hypersensitivity had been attenuated. In agreement
      with these findings, other studies have shown that the induction of endotoxin
      tolerance by MLA parallels the induction of resistance of animals to lethal
      challenges with either Gram negative or Gram positive bacteria. As predicted from
      preclinical studies, human trials of the clinical form of MLA (MPL
      immunostimulant) have confirmed that MLA could attenuate systemic responses to
      endotoxin in normal volunteers, including the attenuation of blood cytokine
      accumulation and attenuation of symptomatic responses.

PMID- 8524965
TI  - Lipopolysaccharides of oral black pigmented bacteria and periodontal diseases. A
      novel immunomodulator different from endotoxin was extracted from Prevotella
      intermedia ATCC 25611 with hot phenol-water.

PMID- 8524966
TI  - The ability of bacteria associated with chronic inflammatory disease to stimulate
      E-selectin expression and neutrophil adhesion.

PMID- 8524967
TI  - Endotoxins in the environment.

PMID- 8524968
TI  - Lipopolysaccharides from Helicobacter pylori.

PMID- 8524969
TI  - Changes of cyclic alternating pattern (CAP) parameters in situational insomnia
      under brotizolam and triazolam.
AB  - The standardized scoring criteria of sleep can serve as a rough tool for
      monitoring the effects of psychoactive compounds, both in normal sleepers and in
      insomniac patients. More sensitive information on the impact of perturbing
      factors and drugs during sleep is supplied by the cyclic alternating pattern
      (CAP) parameters. In particular, CAP rate, which measures the amount of arousal
      instability during NREM sleep, has been proved of high reliability in a variety
      of clinical and pharmacological settings. The present study aimed at evaluating
      the activity of brotizolam (Br) 0.25 mg and triazolam (Tr) 0.25 mg on both
      conventional and CAP parameters in a model of situational insomnia of
      intermediate severity. Six middle-aged healthy subjects (three males and three
      females, aged 40-55 years) with no complaints about sleep, underwent a
      polysomnographic investigation according to a double-blind crossover design:
      placebo without noise (night 1), placebo with noise (night 2), brotizolam or
      triazolam without noise (nights 3 and 5), brotizolam or triazolam with noise
      (nights 4 and 6). The unperturbed nights consisted of standard recording
      conditions in a sound-protected sleep laboratory, whereas situational insomnia
      was accomplished by means of continuous white noise at 55 dBA delivered
      throughout the night. Subjects received medication orally at bedtime. An interval
      of at least 48 h was secured between consecutive recordings in the same
      individual. Compared to baseline conditions, situational insomnia was
      characterized by a shorter amount of total sleep (-40 min) and by an extension of
      intrasleep awakenings (+62 min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524970
TI  - Injections of muscimol into the median raphe nucleus produce hippocampal theta
      rhythm in the urethane anesthetized rat.
AB  - It has previously been shown that serotonergic [5-hydroxytryptamine (5-HT)]
      neurons of the median raphe nucleus (MR) are critically involved in the control
      of the hippocampal electroencephalogram (EEG). Activation of MR 5-HT neurons
      desynchronizes the hippocampal EEG, whereas inhibition of MR 5-HT activity
      produces hippocampal theta rhythm. The MR contains an intrinsic population of
      gamma-aminobutyric acid (GABA) containing neurons that synapse on 5-HT cells of
      the MR. The present study examined the effects on the hippocampal EEG of
      injections of the GABAA agonist muscimol hydrobromide into the MR. Low doses of
      muscimol (0.5 microgram) produced hippocampal theta rhythm at a mean latency of
      6.81 min and for a mean duration of 23.6 min. Higher doses (1.0 microgram and 3.0
      micrograms, respectively) produced theta at mean latencies of 2.24 min and 3.2
      min and for mean durations of 31.84 min and 24.88 min. Injections of muscimol
      into regions adjacent to the MR generated theta at significantly longer latencies
      or were without effect. The present results indicate that MR injections of
      muscimol produce theta by inhibiting the activity of MR 5-HT neurons. It is
      concluded that MR GABAergic systems, via their influence on MR 5-HT cells, serve
      an important role in the control of the hippocampal EEG.

PMID- 8524971
TI  - Acute and subchronic effects of clozapine on licking in rats: tolerance to
      disruptive effects on number of licks, but no tolerance to rhythm slowing.
AB  - In order to assess the effects of the atypical neuroleptic clozapine on
      orolingual competence in rats, tongue function was measured by quantitating the
      rhythm of tongue movements after acute (1.0, 3.0, 6.0 mg/kg) or subchronic
      intraperitoneal treatment (1.5, 3.0, 4.5 mg/kg, each dose for at least 7 days)
      with the drug. Thirsty rats were trained to lick water from a force-sensing disk
      by thrusting the tongue through a 12-mm-diameter hole to strike the horizontal
      disk located 5 mm below the hole. Number of licks in 2 min and rhythm of tongue
      movements (as determined by Fourier analysis of the force-time signal) were each
      dose dependently reduced in the acute dose-effect phase of the study. In the
      subchronic study number of licks exhibited tolerance, but the slowing of lick
      rhythm did not show tolerance. An acute dose range of the serotonin antagonist
      ritanserin (0.5, 1.0, 2.0, 4.0 mg/kg) was also studied in the same rats.
      Ritanserin had no effect on any of the measures of orolingual function. The
      clozapine result was replicated in a second study using younger, drug naive rats.
      The results for clozapine were contrasted with previous reports indicating that
      haloperidol has little effect on lick rhythm. Additional discussion evaluated the
      possible contribution of neurotransmitter receptors on motor neurons of the
      hypoglossal nucleus to the observed rhythm slowing induced by clozapine.

PMID- 8524972
TI  - Improvement in performance of a delayed matching-to-sample task by monkeys
      following ABT-418: a novel cholinergic channel activator for memory enhancement.
AB  - ABT-418, a newly characterized centrally acting cholinergic channel activator
      (ChCA), was evaluated for its ability to improve performance in a delayed
      matching-to-sample (DMTS) task by mature macaques well trained in the task.
      Previous studies in rodents have indicated that ABT-418 shares the
      memory/cognitive enhancing actions of nicotine, but without many of nicotine's
      dose-limiting side effects. As DMTS provides a measure both of general cognitive
      function (the matching concept) and of recent memory, it was hypothesized that
      some doses of ABT-418 would enhance the monkeys' ability to correctly perform the
      DMTS task. Intramuscular administration of ABT-418 significantly enhanced DMTS
      performance at low (2-32.4 nmol/kg) doses. In fact, the drug was slightly more
      potent that nicotine in this regard, and all eight animals tested in this study
      exhibited enhanced performance at one or more doses. ABT-418 produced the
      greatest improvement in DMTS performance at the longest delay interval. In
      animals repeatedly tested with their individualized "Best Dose", DMTS performance
      increased on average by 10.1 +/- 3.5 percentage points correct, which was
      equivalent to an increase of 16.2% over baseline performance. ABT-418 did not
      significantly affect response times, i.e., latencies to make a choice between
      stimuli, or latencies to initiate new trials. Whereas nicotine enhanced DMTS
      performance both on the day of administration and on the following day (in the
      absence of drug), ABT-418-induced enhanced performance was detected only on the
      day of administration. Finally, single daily administration of the individualized
      best dose in three monkeys over a period of 8 days generally maintained
      enhancement of DMTS performance. Thus, the data were not consistent with the
      development of significant tolerance to the drug's mnemonic actions. In contrast
      to nicotine, no overt toxicity or side effects to acute or repeated
      administration of the drug were noted. Thus, ABT-418 represents a prototype of a
      new class of nicotinic agonists designed for the potential treatment of human
      dementias having a low profile of toxicity.

PMID- 8524973
TI  - Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food
      motivated behavior.
AB  - The current study demonstrates the ability of neuropeptide Y (NPY) to increase
      break points under a progressive ratio 1 (PR1) reinforcement schedule. An initial
      response resulted in delivery of a food reinforcer (45 mg pellet) under the PR1,
      and an additional response was required for each successive reinforcer. The break
      point, the number of responses emitted to obtain the last reinforcer, is
      considered a measure of reinforcing efficacy or motivational strength of the food
      reinforcer. NPY (0.3-10 micrograms) significantly increased break point to levels
      comparable to those produced by 36-48 h of food deprivation. Although insulin (3
      8 U/kg) and 2-deoxyglucose (150-250 mg/kg) also increased food intake, neither
      increased break points to levels produced by NPY or food deprivation. These data
      suggest that NPY may change the value of food in ways that cannot be accounted
      for by changes in insulin, glucose levels or intracellular glucoprivation. These
      results emphasize that simply measuring the amount of freely available food eaten
      is not a fully adequate measure of the strength of the feeding behavior.

PMID- 8524974
TI  - Empirical evidence that the state dependence and drug discrimination paradigms
      can generate different outcomes.
AB  - The study compared the outcomes generated by the State Dependence and Drug
      Discrimination paradigms with ethanol in the rat. Food-deprived rats learned to
      complete a fixed-ratio 10 schedule of bar presses for food within 120 s while
      treated with 320- to 1250-mg/kg doses of ethanol. Subsequent tests of recall of
      this response with saline failed to generate any evidence that transfer was
      hampered following the drug-to-saline state change. In contrast, each of 14 rats
      learned to discriminate 1250 mg/kg ethanol from saline in a Drug Discrimination
      procedure that also required the animals to press one of two levers for food
      according to a fixed- ratio 10 schedule. The results offer the first empirical
      evidence to demonstrate directly that the State Dependence and Drug
      Discrimination paradigms can generate different outcomes in otherwise identical
      experimental conditions.

PMID- 8524975
TI  - Serotonergic modulation of anticholinergic effects on cognition and behavior in
      elderly humans.
AB  - Cholinergic neurotransmission is thought to be modulated by serotonin as
      documented in animal and human studies. We examined the effects of the muscarinic
      antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin
      mixed agonist/antagonist m-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the
      selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal
      elderly volunteers each received five separate pharmacologic challenges (placebo,
      ondansetron, scopolamine, scopolamine+ondansetron, and scopolamine+m-CPP).
      Cognitive, behavioral, and physiologic variables were analyzed using repeated
      measures analysis of variance. The acute effects of scopolamine in certain
      cognitive, behavioral, and physiological measures were significantly exaggerated
      by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by
      ondansetron at the dose tested, nor did ondansetron given alone affect basal
      cognitive performance. This pilot study suggests that the serotonin mixed
      agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes
      associated with the combination of scopolamine and m-CPP do not appear to be
      secondary to simple pharmacokinetic alterations and suggest a complex interaction
      between the cholinergic and serotonergic systems centrally.

PMID- 8524976
TI  - Desire to smoke during spaced smoking intervals.
AB  - This study examined the detailed time course of desire to smoke self-reports
      during brief periods of tobacco smoking deprivation to determine how these
      reports are related to amount and spacing of scheduled smoking. During four
      independent sessions, subjects (n = 10) smoked cigarettes at 30-, 60-, or 120-min
      intervals, or only smoked a single cigarette at the end of the 6-h session. At 15
      min intervals, subjects answered four analog scale questions measuring their
      desire to smoke which were averaged to produce a single score. Mean desire to
      smoke scores were 28, 43, 59 and 71 in the 30-, 60-, 120- and 360-min cigarette
      spacing conditions, respectively, indicating an orderly relationship with amount
      of scheduled smoking. Patterns of change were similar across repeated
      observations and during several different deprivation intervals. Desire to smoke
      ratings, although temporarily suppressed by smoking, began rising within minutes
      of smoking and increased to near maximum levels (about 80 on a 100-point scale)
      after fewer than 3 h of abstinence. The observed rapid escalation in desire to
      smoke ratings during brief periods of abstinence is consistent with cigarette
      craving being reported by regular smokers who are not trying to quit. Further, if
      cravings can be accepted as a feature of tobacco withdrawal, the results support
      the view that avoidance of withdrawal is an important factor that maintains
      regular cigarette smoking.

PMID- 8524977
TI  - Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys
      responding under a progressive-ratio schedule.
AB  - Rhesus monkeys (n = 5) were prepared with chronic IV catheters and trained to
      lever press under a PR schedule of drug injection. The schedule consisted of five
      components, each made up of four trials (i.e., 20 trials total). Each trial
      within a component had the same response requirement. The response requirement in
      the first component was 120/trial and doubled in successive components to a
      maximum of 1920 in the fifth. A trial ended with an injection or the expiration
      of a 12-min limited hold (LH). The inter-trial interval (ITI) was 15 or 30 min.
      Following an injection or expiration of the LH, all stimulus lights were
      extinguished and responding had no consequence for the remainder of the trial. A
      session ended when either all 20 injections were self-administered or the
      response requirement was not met within the LH for two consecutive trials. The
      number of injections/session and responses/session increased with dose for
      cocaine (0.012-0.1 mg/kg per injection) and procaine (0.12-2.0 mg/kg per
      injection) at both ITI values. At the 15-min ITI, responding decreased again at
      higher doses in some monkeys with cocaine and in all monkeys with procaine. At
      maximum, cocaine maintained significantly more injections and responses/session
      when the ITI was 30 min than when it was 15 min. In contrast, the increase in ITI
      did not increase the maximum maintained by procaine. Cocaine was approximately 10
      fold more potent than procaine and maintained at maximum significantly more
      injections and responses than procaine when ITI was 30 min but not when the ITI
      was 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8524978
TI  - The discriminative stimulus effects of methamphetamine in pigeons.
AB  - This experiment was designed to elucidate the neurotransmitter systems that
      mediate the discriminative stimulus effects of methamphetamine. Four pigeons were
      trained to peck one key following saline injections and a second key following
      methamphetamine injections (1.0 or 1.7 mg/kg, IM). Substitution tests revealed
      drug-appropriate responding following administration of the psychomotor
      stimulants methamphetamine, amphetamine and cocaine, the dopamine (DA) reuptake
      inhibitor bupropion, norepinephrine (NE) reuptake inhibitors imipramine and
      tomoxetine, and the serotonin (5-HT) releaser fenfluramine. Saline-key responding
      occurred following administration of the D1 agonist SKF-38393, the D1 antagonist
      SCH-23390, the alpha 2 receptor agonist clonidine, the alpha 1 antagonist
      prazosin, a nonselective beta-antagonist propranolol and the selective 5-HT
      reuptake inhibitor fluoxetine. The D2/D3 agonist quinpirole produced drug
      appropriate responding in two pigeons and partial substitution in the remaining
      two pigeons. The 5HT1A agonist 8-OH-DPAT produced drug-appropriate responding at
      higher doses (0.3-1.0 mg/kg), whereas much lower doses (0.003-1.0 mg/kg)
      antagonized the methamphetamine stimulus. The stimulus effects of methamphetamine
      were attenuated by pretreatment with prazosin, SCH-23390 and eticlopride, whereas
      pretreatment with propranolol and the 5-HT3 antagonist, MDL 72222, failed
      reliably to attenuate drug key responding. These results suggest that NE and DA
      reuptake inhibition and 5-HT release mediate the discriminative stimulus effects
      of methamphetamine as do the 5-HT1A and DA D1 and D2 receptors.

PMID- 8524979
TI  - Contrasting effects of clonidine and diazepam on tests of working memory and
      planning.
AB  - The alpha 2 adrenoceptor has recently been implicated in working memory (WM), a
      function dependent on the integrity of the prefrontal cortex. Using a double
      blind, placebo-controlled design, the present investigation examines the effects
      of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the mixed alpha 1/alpha
      2 adrenoceptor agonist clonidine (CLO) on performance of various computerised
      tests of WM and planning in healthy, young volunteers. These are compared to the
      effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the
      same set of neuropsychological tests in a comparable set of subjects.
      Administration of CLO resulted in impulsivity of responding in a planning task,
      as well as differential dose-dependent effects on two analogous tests of spatial
      and visual WM. The nature of these effects were suggestive of mnemonic, rather
      than executive, dysfunction. Conversely, DZP produced specific deficits on tests
      of spatial WM and planning very similar to those seen following lesions to the
      frontal lobes. Therefore, these two sedative drugs produce doubly dissociable,
      dose-dependent effects on different aspects of cognitive function.

PMID- 8524980
TI  - Clonidine and diazepam have differential effects on tests of attention and
      learning.
AB  - The noradrenergic system has repeatedly been implicated in the mediation of
      attentional processes. Using a double-blind, placebo-controlled design, the
      present investigation examines the effects of two doses (1.5 micrograms/kg and
      2.5 micrograms/kg) of the alpha 2 adrenoceptor agonist clonidine (CLO) on
      performance of various computerised tests of attention and learning in healthy,
      young volunteers. These are compared to the effects produced by two doses (5 mg
      and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests
      in a comparable set of subjects. Both doses of CLO were found to impair
      performance of the RVIP test of sustained attention, while the higher dose alone
      improved visuo-spatial learning. Conversely, the higher dose of DZP produced
      profound deficits on visuo-spatial learning, and impaired attentional set
      shifting. This study suggests a role for the alpha 2 adrenoceptor in selective
      attention, and for the benzodiazepine receptor in specific cognitive processes
      mediated by discrete cortical regions.

PMID- 8524981
TI  - Electroconvulsive shock increases dopamine D1 and D2 receptor mRNA in the nucleus
      accumbens of the rat.
AB  - The present study examined the effects of acute and repeated administration of
      electroconvulsive shock (ECS) on levels of D1 and D2 receptor mRNAs in the
      nucleus accumbens and striatum (caudate-putamen) of the rat. Quantitative in situ
      hybridisation with 35S-labelled oligonucleotide probes specific for D1 and D2
      receptor mRNAs was utilised. Compared to controls, rats receiving a single ECS
      showed higher levels of both D1 and D2 receptor mRNAs in the nucleus accumbens 4
      h, but not 24 h, after treatment. Similarly, rats receiving ECS repeatedly (five
      ECS in 10 days) also exhibited higher levels of D1 and D2 receptor mRNAs in the
      nucleus accumbens 4 h, but not 24 h, after the last treatment. The effects of
      single and repeated ECS treatment on dopamine receptor mRNA levels were localised
      to the caudal region of the nucleus accumbens. No statistically significant
      changes in mRNA levels were detected in the striatum of rats treated with either
      acute or repeated ECS. We discuss the possibility that increased expression of D1
      and D2 receptors in the nucleus accumbens may be involved in the dopamine
      enhancing properties of ECS detected in behavioural studies.

PMID- 8524982
TI  - Oral self-administration of sweetened nicotine solutions by rats.
AB  - Oral self-administration of sweetened nicotine solutions in rats was studied in
      two ways. In the first experiment, one group had continuous access to a water
      bottle containing a sucrose solution and nicotine (10 micrograms/ml), while
      another group had access to an identical sucrose solution without nicotine. All
      rats had continuous access to water. While consumption of nicotine increased with
      increasing concentrations of sucrose, consumption of the sucrose+nicotine
      solution never exceeded the intake of sucrose alone. In subsequent experiments,
      the delivery of the solutions was made contingent upon an operant response. The
      sucrose+nicotine solution was found to maintain responding to higher
      response/reinforcer ratios than the sucrose only solution. These data demonstrate
      that rats will self-administer sweetened nicotine solutions and that
      sucrose+nicotine solutions are more reinforcing than sucrose solutions alone.
      Free access consumption is not a good predictor of the response maintaining
      properties of nicotine solutions.

PMID- 8524983
TI  - Dopamine depletion augments endogenous opioid-induced locomotion in the nucleus
      accumbens using both mu 1 and delta opioid receptors.
AB  - The aim of this study is to analyze further the opioid receptor subtypes involved
      in the augmentation of behavioral activity after dopamine depletion in the
      nucleus accumbens of rats. Initially, the opioid receptors involved in the
      augmentation of locomotion produced by endogenous opioids were evaluated by
      microinjection of kelatorphan, an inhibitor of proteolytic enzymes that
      inactivates enkephalin, with or without specific antagonists for mu 1 or delta
      opioid receptors, naloxonazine or naltrindole, respectively. Kelatorphan produced
      a dose-dependent increase in horizontal photocell counts and vertical movements.
      At all doses examined the behavioral response was augmented in rats sustaining
      accumbal dopamine lesions. The augmentation in dopamine-depleted rats was
      partially blocked by naloxonazine or naltrindole. Since the motor stimulant
      response to intra-accumbens microinjection of the delta-opioid agonist, [D
      penicillamine2,5]-enkephalin, was not augmented in a previous study, we tested
      the behavioral response to a new endogenous delta-opioid agonist, [D-Ala2]
      deltorphin I. The locomotor response to deltorphin was slightly augmented in
      dopamine-depleted rats. These data suggest that the augmentation in the motor
      response elicited by endogenous opioids after dopamine lesions in the nucleus
      accumbens involves both mu 1, and delta-opioid receptors.

PMID- 8524984
TI  - Complex effects of age and gender on hypothermic, adrenocorticotrophic hormone
      and cortisol responses to ipsapirone challenge in normal subjects.
AB  - The effects of a challenge dose of the 5-HT1A agonist, ipsapirone (0.3 mg per kg
      body weight), or placebo on body temperature and on adrenocorticotrophic hormone
      (ACTH) and cortisol release, were examined in 30 normal subjects (14 males, 19-74
      years and 16 females, 22-69 years) using a randomized, double blind design.
      Irrespective of age or gender, ipsapirone induced a significant reduction in body
      temperature relative to placebo and a significant increase in ACTH and cortisol
      release. Maximal temperature reduction by ipsapirone was significantly blunted in
      older subjects and was inversely related to age. There was no gender difference
      in the hypothermic response to ipsapirone. ACTH and cortisol responses showed an
      opposite impact of aging in males and females. Whereas both responses diminished
      with age in male subjects, they increased with age in females. The cortisol
      response of older females was significantly larger than that of all the other
      subjects. Adverse effects of ipsapirone were also more marked in elderly females
      and were correlated with ACTH and cortisol responses. These findings should be
      taken into consideration in the use of ipsapirone and other 5-HT1A agonists as
      challenge procedures for studying central serotonergic function in depression and
      other disorders. Careful matching of control and experimental subjects is
      indicated so as to avoid spurious results which reflect the effects of age and
      gender rather than the pathophysiology of the disorders being investigated.

PMID- 8524985
TI  - D4 dopamine receptor binding affinity does not distinguish between typical and
      atypical antipsychotic drugs.
AB  - The affinities of 13 atypical and 12 typical antipsychotic drugs for the cloned
      rat D4 dopamine receptor and the D4/D2 ratios were examined. Of the atypical
      antipsychotic drugs tested, only clozapine, risperidone, olanzapine, zotepine and
      tiospirone had affinities less than 20 nM. In fact, many atypical antipsychotic
      drugs had relatively low affinities for the cloned rat D4 receptor, with Ki
      values greater than 100 nM (Seroquel, fluperlapine, tenilapine, FG5803 and
      melperone). Additionally, several typical antipsychotic drugs had high affinities
      for the cloned rat D4 receptor, with Kis less than 20 nM (loxapine,
      chlorpromazine, fluphenazine, mesoridazine, thioridazine and trifluoroperazine).
      The ratios of D2/D4 affinities did not differentiate between these two types of
      antipsychotic drugs. Thus, D4 dopamine receptor affinity, used as a single
      measure, does not distinguish between the group of typical and atypical
      antipsychotic drugs analyzed.

PMID- 8524986
TI  - Words and sentences: event-related brain potential measures.
AB  - Interactions between sentences and the individual words that comprise them are
      reviewed in studies using the event-related brain potential (ERP). Results
      suggest that, for ambiguous words preceded by a biasing sentence context, context
      is used at an early stage to constrain the relevant sense of a word rather than
      select among multiple active senses. A study comparing associative single-word
      context and sentence-level context also suggests that sentence context influences
      the earliest stage of semantic analysis, but that the ability to use sentence
      context effectively is more demanding of working memory than the ability to use
      single-word contexts. Another indication that sentence context has a dramatic
      effect on single-word processing was the observation that high- and low-frequency
      words elicit different ERPs at the beginnings of sentences but that this effect
      is suppressed by a meaningful sentence context.

PMID- 8524987
TI  - Somatosensory responses during selective spatial attention: The N120-to-N140
      transition.
AB  - The somatosensory evoked potential negative components in the 100-150-ms range
      were studied under conditions where attention was directed either toward or away
      from the probe stimulus. An N120 component, not sensitive to spatial attention,
      appeared in all conditions, including the no-task condition. Its distribution was
      consistent with an origin in the second somatic area. A later N140 response, not
      recorded in neutral conditions, was highly sensitive to spatial attention and
      reached its maximum to stimulation of the attended hand; its behavior was
      consistent with that of a processing negativity. The N140 was bilaterally
      distributed, but the hemisphere contralateral to stimulation appeared to be
      involved earlier than the ipsilateral one. Although the exogenous N120 may be
      influenced by somatosensory awareness and perhaps tactile recognition, the N140
      appears linked to the spatial components of attention and results from the
      activation of several areas in both hemispheres.

PMID- 8524988
TI  - Time course and mechanisms of decreased plasma volume during acute psychological
      stress and postural change in humans.
AB  - In this study, we examined the effects of psychological stress on calculated
      plasma volume, the relationship of these changes to changes in hematologic and
      hemodynamic factors, and the time course of plasma volume changes. Plasma volume
      changes were assessed using mass densitometry techniques, which measured changes
      in blood and plasma density. Hematologic and hemodynamic variables were assessed
      in 40 healthy men and women during a mental arithmetic (math) or benign reading
      task and during postural change (standing). Results indicated that math and
      posture change produced a significant decrease in plasma volume (ps < .001) and
      increases in blood pressure (ps < .001), blood and plasma density (ps < .001),
      and total plasma protein (p < .001). Correlations were observed between plasma
      volume changes and changes in systolic (r = .55, p < .0001), diastolic (r = .61,
      p < .0001), and mean (r = .65, p < .0001) arterial pressure during math; plasma
      volume and blood pressure returned to baseline within 12 min following the math
      task. These results suggest that an important mechanism for stress-induced
      decreases in plasma volume is increased blood pressure leading to increased fluid
      shifts from the vasculature into the interstitial spaces.

PMID- 8524989
TI  - Spatial orienting and focused attention in attention deficit hyperactivity
      disorder.
AB  - Seventeen children with attention deficit disorder (ADHD) and 10 normal controls
      performed two tasks while event-related potentials were recorded. ADHD subjects
      took part in two more sessions under methylphenidate (MP) or placebo. In the
      spatial orienting task, invalidly cued targets elicited a longer reaction time
      (RT) and a P3 that was longer in latency and greater in amplitude than did
      validly cued targets. Performance was similar for both groups, but the early
      portion of P3 (300-400 ms) was lower in amplitude for invalidly cued targets in
      ADHD subjects. MP increased accuracy without affecting RT and shortened P3 peak
      latency and increased the amplitude of its early portion. In the focused
      attention task, accuracy was greater for controls and MP, but there were no RT
      differences. Attended stimuli elicited greater amplitude P1, N1, and P3 than did
      nonattended stimuli, but these measures were unaffected by diagnosis or
      medication.

PMID- 8524990
TI  - Variation in the latencies and amplitudes of N400 and NA as a function of
      semantic priming.
AB  - The purpose of this study was to determine whether the latencies of two event
      related potential (ERP) components, the NA and N400, were sensitive to semantic
      priming. Subjects performed a semantic judgment task, which was designed in such
      a way that the N400 could be examined without overlap from the P3. Priming
      effects on the latencies of both NA and N400 were most apparent at frontocentral
      sites. The amplitude of NA was not significantly affected by priming. The
      amplitude of N400 was smaller for primed than for unprimed words, but the effect
      was significant only at centroposterior sites. Current source density (CSD)
      analyses performed on the ERP data suggested the activation of multiple
      generators in the N400 time region. The ERP and CSD data were consistent with the
      existence of two types of N400, a frontal N400 that varies in latency as a
      function of semantic priming, and a posterior N400 that varies in amplitude.

PMID- 8524991
TI  - Parental history of hypertension and enhanced cardiovascular reactivity are
      associated with decreased pain ratings.
AB  - Ischemic pain was examined in adult males with and without a parental history of
      hypertension. Blood pressure and heart rate were recorded during baseline, cold
      pressor, and ischemia. Repeated pain ratings were obtained during cold pressor
      and ischemia, and the McGill Pain Questionnaire was completed after each
      stressor. A median split was used to identify high and low mean arterial pressure
      and heart rate reactors to cold pressor. Parental history of hypertension, high
      heart rate reactivity, and high mean arterial pressure reactivity were each
      associated with significantly lower ischemic pain ratings on the McGill Pain
      Questionnaire, suggesting that risk for hypertension is associated with
      hypoalgesia in normotensives.

PMID- 8524992
TI  - Changes in brain activity patterns in aging: the novelty oddball.
AB  - A decrease in the frontal lobes' efficiency is supposed to play a role in age
      related changes in cognitive function. If frontal lobes are involved in the
      maintenance of working memory, the elderly may require increased frontal activity
      because of more rapid memory decay. This is consistent with the fact that the P3
      component of the event-related potential (ERP) has a more frontal orientation
      with increasing age. However, frontally distributed P3s are also observed in
      young people when novel stimuli are unexpectedly presented in an oddball
      paradigm. Young and old subjects were run in an auditory novelty oddball in which
      ERPs were recorded from 30 scalp sites. The young adults' P3s showed either a
      posterior (targets) or more frontally oriented (novels) scalp focus. The elderly
      were less accurate in their memory for the novel stimuli, and their P3s showed
      anterior and posterior foci to both targets and novels. The young adults' target
      P3s changed over time from a frontal to a posterior focus, whereas the old
      adults' did not. These results are consistent with decreased ability of the
      elderly to maintain the templates needed for stimulus categorization.

PMID- 8524993
TI  - Graham named recipient of the Gold Medal Award for Life Achievement in
      Psychological Science by the American Psychological Association.

PMID- 8524994
TI  - [Beta-lactamase and its molecular evolution].

PMID- 8524995
TI  - [Novel NAD(+)-cleavage enzymes possibly involved in signal transduction system].

PMID- 8524996
TI  - [Spermatogenesis in amphibians analyzed by culture systems].

PMID- 8524997
TI  - [Kinetic analysis of enzyme reactions within cells].

PMID- 8524998
TI  - [Toward the treatment of obesity: role of PPAR gamma in adipogenesis].

PMID- 8524999
TI  - [Direct analysis of the peptide bond cleavage by rapid quenching method].

PMID- 8525000
TI  - [Interpretation of diagnostic data exemplified by tests for identification of
      Helicobacter pylori in gastric mucosa].
AB  - Seven diagnostic tests were employed to detect the infection of gastric mucosa
      with the H. pylori bacteria, among patients with epigastric pain and dyspeptic
      complains. The tests' results were compared to the bacteriologic culture. For
      each test the following criteria were taken into consideration: sensitivity,
      specificity, positive and negative predictive values. The tests' accuracy was
      compared with the agreement expected by chance and beyond chance (kappa). For
      each test the likelihood ratio was calculated for its positive and negative
      results. The construction of so called diagnostic decision tree was presented,
      which allows on the evaluation of the diagnostic test and its utility. The best
      result were obtained from the test, in which the identification of bacteria took
      place in the histopathologic specimen after its Gram staining. The interpretation
      of clinical significance of diagnostic data is simplified with the use of
      likelihood ratio calculated for a positive test result.

PMID- 8525001
TI  - [Late hematologic status after chemotherapy observed in patients 3 to 10 years
      after treatment].
AB  - The aim of the present study is the evaluation of late hematological complication
      in patients who received aggressive chemotherapy, and were observed 3, 5 and 10
      years after treatment was completed. In the group of 35 patients, besides high
      percent of early hematological complications, there was only one case of anemia
      grade 2 (acc. to WHO score). We concluded that the hematological recovery after
      aggressive chemotherapy was satisfactory. No secondary hematological malignancies
      have been found.

PMID- 8525002
TI  - [Proliferative mesangial glomerulonephritis (PMGN) and IgA nephropathy (IgAGN).
      Immunohistochemical comparative analysis of cellular infiltrates and clinico
      morphological correlations].
AB  - Glomerular and interstitial leukocyte subpopulations were analyzed in renal
      biopsies from 20 patients with proliferative mesangial glomerulonephritis (PMGN)
      and from 20 patients with IgA nephropathy (IgAGN), by immunoperoxidase techniques
      with monoclonal antibodies. Few; intraglomerular leukocytes were seen, the
      majority of them belonging to the monocyte/macrophage phenotype. T-cells and
      monocyte/macrophages constituted the predominant infiltrating cell type in the
      interstitium. Significant differences were found in the numbers of
      intraglomerular macrophages between PMGN and IgAGN, and in the numbers of T-cells
      between IgAGN and control group. Rang Spearman Correlations showed proteinuria
      values in PMGN to be closely dependent on density of intraglomerular infiltrates
      and the number of macrophages. Hematuria values in IgAGN were closely dependent
      on the number of intraglomerular macrophages. Interstitial macrophages and T
      cells were well correlated with the degree of interstitial damage and the serum
      creatinine level in PMGN and in IgAGN. No association was found between
      intraglomerular cells and serum creatinine level, and between interstitial cells
      and proteinuria values, as well hematuria values at the time of biopsy. These
      findings suggest that mononuclear cells may play a role in the pathogenesis of
      PMGN and IgAGN, and that cellular immune mechanisms may be important determinants
      of the severity of histological lesions and the degree of renal function.

PMID- 8525003
TI  - [Congenital and acquired cytomegalovirus infection in infants confirmed by
      virologic studies].
AB  - Sixty infants in whom clinical symptoms suspected of cytomegalovirus (CMV)
      infection were studied. CMV infection was found in 50% of the subjects. The
      diagnosis was based on studies of specific antibodies and isolation of the virus
      from urine and/or throat swabs. In most of the children the examinations were
      repeated several times, and clinical observations continued for 1 to 42 months
      (avg. 18 months). IgM-class antibodies were detected in 26 children and in 18 the
      virus was isolated. In 3 infants, isolation of CMV virus was the only evidence of
      active infection. Persisting viruria (avg. 11 months) and long-term presence of
      Ig G antibodies, even to 44th month of life were also observed. Congenital
      infection was diagnosed in 4 infants; the remaining ones acquired the infection
      during the perinatal period or later. In 7 cases transfused blood cannot be
      excluded as the source of infection. The clinical symptoms manifested in infected
      and non-infected children were similar. There was a statistically significant
      increase in the occurrence of hepatomegaly, splenomegaly, hyperbiliru-binemia and
      diarrhoea in infected children. Congenital abnormalities were found in 10
      infected children, including 4 cases of congenital cytomegaly.

PMID- 8525004
TI  - [Impaired gallbladder motility--an underestimated pathogenetic factor of
      gallstones].

PMID- 8525005
TI  - [Helicobacter pylori and its role in gastric and duodenal ulcers].

PMID- 8525006
TI  - [Bone metastasis: pathomechanism and treatment procedures].

PMID- 8525007
TI  - [Circulating immune complexes in airborne allergy--a protective role?].
AB  - Circulating immune complexes (KI) were analyzed in 78 patients with airborne
      allergy and compared to 34 persons of control group. KI were isolated by
      precipitation with 3% polyethylene glycol. KI-IgG, KI-IgA, KI-IgM were measured
      by radial immunodiffusion, KI-IgE by an immunofluorometric assay. Staphylococcal
      Protein A (SpA) binding to KI was measured by ria. Relations between the level of
      various KI and the diagnosis of allergic disease, the kind of allergen (related
      also to the exposition) and the symptoms of atopy were evaluated. Serum levels of
      KI-IgE, KI-SpA, and KI-IgM were distinctly elevated in airborne allergy, with the
      positive correlation between KI-SpA and KI-IgM. KI-IgE were related to the kind
      of sensitizing allergen and to the exposition to the pollen allergens. Most
      distinct differences in KI level were observed not in relation to the kind of
      disease or of the sensitizing allergen, but in relation to the symptoms and
      intensiveness of atopy. Patients showing a greater number and intensiveness of
      symptoms exhibited higher levels of KI-SpA. However, one of the symptoms scored
      (dyspnea) was connected with the decreased level of KI-SpA in these patients. We
      interpret the results in favour of the hypothesis of the dual role of KI in
      airborne allergy. We propose a protective role for KI-Spa, which contain IgG and
      may bind IgE, thus protecting the target organs of allergy.

PMID- 8525008
TI  - [Continued study of factors influencing the amount of shear wall stress in the
      acute phase of ischemic stroke].
AB  - In 36 patients with the acute ischemic stroke a significant decrease of level of
      apo A1 and HDL was indicated. Patients with transient ischemic attacks had
      significantly higher level of trigliceryde in blood than those with completed
      stroke. High significant correlations between level of fibrinogen and thixotropic
      effects/value of yield shear on 100 of a cortain biochemical factor/ of apo A1
      and albumin were also indicated. The lack of these correlations in controls
      suggested a role of unknown factors in the red cells and fibrinogen interaction
      connected with ischemic disorders. The close study of these processes should lead
      to improve an efficiency of the treatment and prophylaxis of ischemic stroke by
      means of specific drugs.

PMID- 8525009
TI  - [Adhesion and aggregation of neutrophils in patients with unstable angina].
AB  - The adherence and aggregation abilities of neutrophils (PMNs) were evaluated in
      thirty three patients with unstable angina, who were qualified for PTCA
      procedure. The control group consisted of forty one clinically healthy persons.
      The blood for investigations was obtained from coronary sinus and basilic vein
      just before the procedure, while in the control group from basilic vein only. The
      adherence of PMNs to plastic surface (rest and stimulated by PMA) was estimated
      in vitro according to Oez's et al. method by measuring optical density of
      generated formazan, whereas the aggregation of PMNs was evaluated using the
      leukergy test according to the method of Fleck in Berliner's and Aronson's
      modification. In patients with unstable angina statistically significant higher
      (p < 0.001) adherence of peripheral blood PMNs, compared with control groups was
      found (patients: rest-0.525 +/- 0.245, stimulated-0.839 +/- 0.419, control group:
      rest-0.260 +/- 0.129, stimulated-0.522 +/- 0.377). The aggregation of peripheral
      blood PMNs was significantly higher (p < 0.05) in the sick than in the control
      group (the sick-10.98 +/- 4.29%, controls-4.65 +/- 3.01%). No differences in
      investigated parameters of PMNs obtained from peripheral or coronary sinus blood
      were found.

PMID- 8525010
TI  - [Evaluation of the usefulness of stress tests in diagnosis of thoracic outlet
      syndrome with upper limb ischemia].
AB  - The analysis of the stress manoeuver tests in patients with upper limb ischemia
      due to the thoracic outlet syndrome (TOS) was performed. Stress manoeuvre tests
      (Adson, hiperabduction, costo-clavicular, modified Adson test and AER test) were
      found useful in the diagnosis of TOS. However they do not allow to differentiate
      the mechanism of compression. It is important to observe the clinical symptoms of
      arm ischemia during the time of manoeuvre performance. The positive result of the
      one test only, especially AER or modified Adson test has little diagnostic value.

PMID- 8525011
TI  - [The role of serum markers in diagnosis and treatment monitoring in patients with
      lung cancer].

PMID- 8525012
TI  - [Current views on the clinical significance of coronary artery spasm].
AB  - Current views about etiology, pathogenesis, diagnostics and treatment of coronary
      artery spasm have been presented. A lot of researches show complexity of factors,
      which are responsible for coronary artery spasm. The most important are: a local
      hypersensitivity of vessels wall, neurogenic factors and humoral factors. The
      lack of magnesium plays also important role. Clinical manifestations of coronary
      artery spasm are: Printzmetal's angina, arrhythmia, acute myocardial infarction,
      atypical chest pain and cardiac sudden death. Among diagnostic examination the
      main importance have provocative tests with ergonovine and acetylcholine, rarely
      hyperventilation and cold are used. Calcium channel blockers, nitrate,
      molsidomine are employed in treatment patients with coronary artery spasm. There
      are taken modern examinations of new drugs like beta-1 adrenergic agonists and
      derived molsidomine agents. Beta-adrenergic blocking agents are contraindicated.
      It has been emphasized, that early diagnostics and pharmacologic treatment
      improve long-term prognosis in this group of patients.

PMID- 8525013
TI  - [Gamma delta lymphocytes].

PMID- 8525014
TI  - [Bronchoconstriction symptoms mimicking bronchial asthma--report of two cases].
AB  - Two patients sent to the clinic with incorrectly diagnosed asthma have been
      presented. In both cases the bronchospastic symptoms was caused by the obstacle
      in the airways. The authors concluded that there is a great necessity to conduct
      the discriminating diagnosis of bronchospastic symptoms.

PMID- 8525015
TI  - [Autoimmune hemolytic anemia during the course of pancreatic abscess--case
      history].

PMID- 8525016
TI  - [Hematologic disturbances in patients with nonhematologic neoplasms. I. Anemias].

PMID- 8525017
TI  - [Hematologic disturbances in patients with nonhematologic neoplasms. II.
      Thrombosis, bleedings and leukemoid reaction].

PMID- 8525018
TI  - [Remembrances of Dr. A.J. Rolle in the Museum of the Medical Faculty of
      Jagellonian University and his ideal widow].
AB  - Antoni J. Rolle (1829-1894) physician, writer and historian was living in
      Kamieniec Podolski. Many remembrances of Rolle his wife Idalia presented to the
      Museum of the Medical Faculty of Jagellonian University. Centernary of Rolle's
      death occurs the opportunity to remember this eminent personality.

PMID- 8525019
TI  - [Antoni J. Rolle's scientific work in the field of medicine].
AB  - Antoni Jozef Rolle (1829-1894) doctor, social worker, historia, is famous for his
      historical thesis in Polish literature. The composition regards his medical work.
      His greatest papers are about problems in which he was particularly interested:
      psychiatry, prostitution and in veneral diseases. Besides he wrote about social
      problems (hygiene, epidemiology), statistics, the history of medicine.

PMID- 8525020
TI  - EORTC guidelines for writing protocols for clinical trials of radiotherapy.
AB  - The concept of a Master Protocol for phase III studies was raised at the Steering
      Committee of the EORTC Radiotherapy Group, in order to make the work of the study
      coordinators easier, when writing protocols and to give them more homogeneity.
      The Master Protocol defines and clarifies in a logical order the different steps
      which must be taken when designing a randomized trial--from the rationale to the
      references. It pays particular attention to eligibility criteria, volumes of
      interest defined in agreement with ICRU Report 50 (gross tumor volume, clinical
      target volume, planning target volume and organs at risk), simulation procedure,
      treatment technique, normal tissue sparing, dose computation, equipment, dose
      specification (also in agreement with ICRU Report 50). Last but not least, the
      different procedures of quality assurance for protocols and patients are also
      defined (site visits, dummy run procedure, in vivo dosimetry, individual case
      review) to allow working plans to be made in advance. We are aware that this work
      is not exhaustive, but hope that the contents will be of help to those who are
      writing a protocol.

PMID- 8525021
TI  - Estimation of overall pulmonary function after irradiation using dose-effect
      relations for local functional injury.
AB  - PURPOSE: To predict the pulmonary function 3-4 months after irradiation for
      malignant lymphoma from the three-dimensional (3-D) dose distribution. METHODS:
      Dose-effect relations for the relative reduction of local perfusion (Q) and local
      ventilation (V), were calculated in 25 patients, using correlated SPECT (Single
      Photon Emission Computed Tomography) and CT data. By combining the 3-D dose
      distribution of an individual patient with the dose-effect relations averaged
      over all patients, the average reduction of local Q and V (i.e., the overall
      response parameters) in the whole lung was estimated for each patient.
      Correlation coefficients were calculated between these overall response
      parameters and the change in standard lung function tests. In addition, the
      relation between the overall response parameters and the incidence of radiation
      pneumonitis was determined. RESULTS: The overall response parameter for perfusion
      was correlated with the change in standard lung function tests, with correlation
      coefficients varying between 0.53 (p = 0.007) and 0.71 (p < 0.001) for the change
      of Vital Capacity and Forced Expiratory Volume at 1 s, respectively. For the
      overall response parameter for ventilation similar correlations were observed.
      Four out of the 25 patients developed radiation pneumonitis; in these four
      patients the overall response parameter for perfusion was on average somewhat
      higher (13.2 +/- 1.4% (1 standard error of the mean)) than in patients without
      radiation pneumonitis (10.5 +/- 1.0%), but this difference was not significant. A
      higher incidence of radiation pneumonitis was observed for larger values of the
      overall response parameter for perfusion; in patient groups with an overall
      response parameter for perfusion of 0-5%, 5-10%, 10-15%, and 15-20%, the
      incidence of radiation pneumonitis was 0 (0/1), 10 (1/10), 13 (1/8) and 33%
      (2/6), respectively. CONCLUSION: By combining the 3-D dose distribution with the
      average dose-effect relations for local perfusion or ventilation, an overall
      response parameter can be calculated prior to irradiation, which is predictive
      for the radiation-induced change in the overall pulmonary function, and possibly
      for the incidence of radiation pneumonitis, in this group of patients.

PMID- 8525022
TI  - Effect of time, dose and fractionation on local control of nasopharyngeal
      carcinoma.
AB  - To study the effect of radiation factors on local control of nasopharyngeal
      carcinoma, 1008 patients with similarly staged T1N03M0 disease (Ho's
      classification) were retrospectively analyzed. All patients were treated by
      megavoltage irradiation alone using the same technique. Four different
      fractionation schedules had been used sequentially during 1976-1985: with total
      dose ranging from 45.6 to 60 Gy and fractional dose from 2.5 to 4.2 Gy. The
      median overall time was 39 days (range = 38-75 days). Both for the whole series
      and 763 patients with nodal control, total dose was the most important radiation
      factor. The hazard of local failure decreased by 9% per additional Gy (p < 0.01).
      Biological equivalents expressed in terms of Biologically Effective Dose or
      Nominal Standard Dose also showed strong correlation. Fractional dose had no
      significant impact. The effect of overall treatment time was insignificant for
      the whole series, but almost reached statistical significance for those with
      nodal control (p = 0.06). Further study is required for elucidation, as 85% of
      patients completed treatment within a very narrow range (38-42 days), and the
      possible hazard is clinically too significant to be ignored.

PMID- 8525023
TI  - Three-dimensional treatment planning and conformal radiation therapy: preliminary
      evaluation.
AB  - Preliminary clinical results are presented for 209 patients with cancer who had
      treatment planned on our three-dimensional radiation treatment planning (3-D RTP)
      system and were treated with external beam conformal radiation therapy. Average
      times (min) for CT volumetric simulation were: 74 without or 84 with contrast
      material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78
      for treatment planning; 53 for plan evaluation/optimization; and 58 for
      verification simulation. Average time of daily treatment sessions with 3-D
      conformal therapy or standard techniques was comparable for brain, head and neck,
      thoracic, and hepatobiliary tumors (11.8-14 min and 11.5-12.1, respectively). For
      prostate cancer patients treated with 3-D conformal technique and Cerrobend
      blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min
      and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or
      lower than with standard techniques. Sophisticated 3-D RTP and conformal
      irradiation can be performed in a significant number of patients at a reasonable
      cost. Further efforts, including dose-escalation studies, are necessary to
      develop more versatile and efficient 3-D RTP systems and to enhance the cost
      benefit of this technology in treatment of patients with cancer.

PMID- 8525024
TI  - Response of rat spinal cord to very small doses per fraction: lack of enhanced
      radiosensitivity.
AB  - Our previous work with rat spinal cord demonstrated that the linear quadratic
      (LQ) model based on data for large fraction sizes (alpha/beta of 2.4 Gy) failed
      to predict isoeffective doses between 1 and 2 Gy per fraction, and under
      estimated the sparing effect of small doses per fraction given once daily. In
      contrast, data from mouse skin and kidney, and recent in vitro results revealed a
      paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess
      whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per
      fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily
      doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by
      graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy
      fractions given once daily. To limit the overall treatment time to < or = 8
      weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily
      with an interfraction interval of 16 h. The end-point was forelimb paralysis
      secondary to white matter necrosis, confirmed histologically. The ED50 values,
      excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a
      single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions,
      respectively. The data gave an alpha/beta of 2.1 Gy (95% CI, 1.4, 2.7 Gy).
      Pooling the data separately, the alpha/beta value was 2.3 Gy (95% CI, 0.82, 3.7
      Gy) for fraction sizes > or = 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8
      , 0.6- and 0.4-Gy experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525025
TI  - Effect of intra-peritoneal fludarabine on rat spinal cord tolerance to
      fractionated irradiation.
AB  - The effect of fludarabine (9-beta-D-arabinosyl-2-fluoroadenine-5'-
      monophosphate), an adenine nucleoside analogue, on the tolerance of the spinal
      cord to fractionated irradiation was studied in a rat model. Anesthetized female
      Fisher 344 rats received irradiation to 2 cm of the cervical spine with a
      telecobalt unit (dose rate 1.14 Gy/min). Radiation was administered in two, four
      or eight fractions spread over a 48-h period with or without fludarabine. Animals
      assigned to combined therapy received two daily intraperitoneal injections of
      fludarabine (150 mg/kg) given 3 h prior to the first daily radiation fraction. It
      was found that fludarabine reduced the iso-effect dose required to induce leg
      paresis at 9 months after irradiation for all fractionation schedules. Dose
      modification factors of 1.23, 1.29 and greater than 1.27 were obtained for two,
      four and eight fractions, respectively. Fitting the data with the direct analysis
      method of Thames et al. with an incomplete repair model [18] showed that the
      potentiating effect of fludarabine may be mediated through reduction in the
      number of 'tissue-rescuing units' (InK). Alpha and beta values were slightly but
      not significantly decreased, whereas the alpha/beta ratio was unchanged. These
      features suggest that fludarabine did not significantly inhibit cellular repair
      processes but rather reduced the spinal cord tolerance by a fixed additive toxic
      effect on the same target cells. In rodent models, the combination of fludarabine
      and fractionated radiation has previously been found to yield a therapeutic gain,
      i.e., the drug enhanced tumor response to a greater extent than it reduced normal
      tissue tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525026
TI  - Radiation response of murine eccrine sweat glands.
AB  - Following irradiation of the left-hind feet of mice, we measured the ability of
      the eccrine glands to secrete sweat following stimulation by pilocarpine.
      Silicone elastomer impression moulds of the foot pads gave repeatable, detailed
      localization of sweat ducts by retaining the impression of each emerging sweat
      droplet. Loss of gland function occurred rapidly following irradiation (within 2
      weeks) and the rate of loss was dose-dependent, being over three times greater
      following a dose of 13.0 Gy than after 6.8 Gy. There was a dose-dependent nadir
      of function at around 8 weeks, followed by a gradual recovery that was complete
      by about 30 weeks after irradiation, leaving a dose-dependent residual functional
      deficit. Eccrine sweat glands are very radiosensitive organs compared with the
      epidermis. A single dose of 13 Gy resulted in complete loss of eccrine gland
      function at 8 weeks whilst about 23 Gy would be required to elicit transient
      moist desquamation, in oxygen-breathing mice. Substantial sparing was seen when
      two doses were split by intervals of up to 24 h.

PMID- 8525027
TI  - The acceptability of a multileaf collimator as a replacement for conventional
      blocks.
AB  - A multileaf collimator (MLC) can be used as a replacement for conventional blocks
      as well as for conformal radiotherapy. This study has assessed the possibility of
      using a Philips MLC for 218 patients treated with conventionally blocked fields.
      It was found that MLC field shaping would have been appropriate for over 94% of
      such patients. The facility to treat large blocked fields has been found to be
      particularly useful. Use of the predefined shapes stored in the Regular Shape
      Library provided by Philips was evaluated and it was found that an appropriate
      shape was available in 52% of cases. The application of MLC fields to the
      treatment of different anatomical sites is discussed.

PMID- 8525028
TI  - Influence of a sampling review process for radiation oncology quality assurance
      in cooperative group clinical trials--results of the Radiation Therapy Oncology
      Group (RTOG) analysis.
AB  - The Radiation Therapy Oncology Group (RTOG) designed a random sampling process
      and observed its influence upon radiotherapy review mechanisms in cooperative
      group clinical trials. The method of sampling cases for review was modeled from
      sampling techniques commonly used in pharmaceutical quality assurance programs,
      and applied to the initial (on-study) review of protocol cases. 'In control' (IC)
      status is defined for a given facility as the ability to meet minimum compliance
      standards. Upon achieving IC status, activation of the sampling process was
      linked to the rate of continued patient accrual for each participating
      institution in a given protocol. The sampling design specified that > or = 30%
      cases not in compliance would be detected with 80% power. A total of 458 cases
      was analyzed for initial review findings in four RTOG Phase III protocols.
      Initial review findings were compared with retrospective (final) review results.
      Of the 458 cases analyzed, 370 underwent initial review at on-study, while 88 did
      not require review as they were enrolled from institutions that had demonstrated
      protocol compliance. In the group that had both initial and final review, 345/370
      (93%) were found to have followed the protocol or had a minor variation. Of the
      exempted cases, 79/88 (90%) were found to be per protocol or a minor variant. The
      sampling process proved itself to be cost-effective and resulted in a noticeable
      reduction in the workload, thus providing an improved approach to resource
      allocation for the group. Continued evaluation of the sampling mechanism is
      appropriate as study designs and participants vary over time, and as more data
      become available to study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525029
TI  - [Extrapelvic endometriosis involving the perineum].
AB  - The ectopic endometriosis in the perineum is very rare (0.2% of ectopic
      endometriosis). We studied 16 cases of vaginoperineal endometriosis. Fifteen of
      them were localized in the site of an episiotomy scar and in one there was
      another focus of a severe endometriosis of multiple localizations. All the
      patients were submitted to anamnesis, physical, gynecologic and proctologic
      examination, surgical excition, histopathologic study of the lesion and control.
      All the patients are asymptomatic after treatment. To cure definitively the
      disease it is necessary to make a complete ablation of the endometrial lesion.
      Eventually, hormonal treatments could be use in case there were other endometrial
      localizations besides the vaginoperineal one.

PMID- 8525030
TI  - [Endoscopic surgery in ectopic pregnancy. Analysis of 105 cases].
AB  - A report on 105 cases of ectopic pregnancy resolved via endoscopy is presented.
      Surgical techniques for total salpingectomy (82), salpingotomy (11), tubal
      expression (6), partial salpingectomy (3), partial ooforectomy (2) and anexectomy
      (1) is described. The excellent postsurgical recovery and low incidence of
      complications are depicted, as well as the growing percentage of ectopic
      pregnancies resolved endoscopically in our Department.

PMID- 8525031
TI  - [Phyllodes tumor: diagnosis and treatment].
AB  - We reviewed 1.178 benign tumors treated between 1981/93 among which 39 appeared
      with a Phylodes Tumors diagnosis, disregarding 5 of them because they did not
      have a precise description and histologic classification, studying 34 proved
      cases which represented 2.89% of all benign tumors; if we add 89% cancers in
      these years, we have 2.074 and the relation becomes 1.64% of the total. We found
      22 benign phylodes (64.7%) 7 border line (20.5%) and 5 malignant (14.8%) whose
      clinic, histologic and evolutive characteristics are presented in this paper.

PMID- 8525032
TI  - [Blood flow in umbilical artery in fetus with intrauterine growth retardation].
AB  - Many studies of Doppler blood flow velocimetry show an association between
      alteration of flow waves and adverse perinatal outcome in growth retarded fetus.
      In our study, 74 cases of growth retarded fetuses were evaluated with umbilical
      artery Doppler. Sixty-five showed the presence of diastolic flow and all of them
      had good perinatal outcome, regardless the score of the different indexes. On the
      other hand, those cases with absent (7) and reversed diastolic flow (2) were
      correlated with obstetric intervention, low birth weight, neonatal complications
      and perinatal mortality. We conclude that monitoring with umbilical artery
      Doppler in growth retarded fetuses is a good method to detect those who present
      hypoxia.

PMID- 8525033
TI  - [Value of endocervical curettage in colposcopic diagnosis of cervix diseases].
AB  - The present study was undertaken to determine the credibility of endocervical
      curettage as a part of evaluation of patients with abnormal Pap smears. A series
      of 108 patients were carefully examined with colposcopy, ectocervical biopsies
      and endocervical curettage, and all of them underwent cervical conization
      following diagnostic study. The histologic diagnosis results between endocervical
      curettage and cervical cone was compared. The estimate was 85% for sensitivity,
      35% for specificity, 62% for positive predictive value and 65% for negative
      predictive value of cervical curettage. The observations suggest that
      endocervical curettage credibility is poor and we need to asses the outpatient
      evaluation and treatment carefully.

PMID- 8525034
TI  - [Danazol and its effect on bone and lipid metabolism in patients with
      endometriosis].
AB  - Danazol is a synthetic steroid, derived from 17-alpha ethinyltestosterone and it
      is used primarily in the treatment of endometriosis. It effectiveness is due to a
      reversible hypoestrogenic and hyperandrogenic state, which lead to atrophy of the
      ectopic endometrial tissue. A prospective study was undertaken in 14 women of
      child-bearing age with laparoscopically confirmed pelvic endometriosis to
      evaluate the alterations produced in bone and lipid metabolism after a six month
      treatment with Danazol. Laboratory evaluation included: bone mineral density,
      urine hydroxiproline/creatinine and calcium/creatinine ratios, lipid profile,
      bone isoenzyme of alkaline phosphatases and plasma estradiol. A significant
      decrease in plasma estradiol levels was observed (p < 0.001). Decrease in HDL
      cholesterol and increase in LDL cholesterol levels were statistically significant
      after 3 and 6 months of medication (p < 0.001), but the lipoproteins returned to
      normal levels three months after discontinuing Danazol. The bone isoenzyme of
      alkaline phosphatases showed a progressive increase (p < 0.001) and there were no
      significant variations in the hydroxyproline/creatinine and calcium/creatinine
      ratios. The osteodensitometry remained unchanged at 6 months of therapy. We
      conclude that, even though Danazol produces hypoestrogenism and hyperandrogenism,
      the markers of bone loss did not change, it has no negative effect on bone
      mineral density, and the transient worsening of the lipid profile that it causes
      is reversible on discontinuation of medication.

PMID- 8525035
TI  - [Contemporary biopsy for diagnosis of abortion residues: preliminary experience].
AB  - The differential diagnosis between abortion and ectopic pregnancy has important
      clinical implications. In this report we have tested the accuracy of frozen
      sections in uterine curettings to identify intrauterine pregnancy. Uterine
      curettings with a diagnosis of products of gestation, from 104 patients were
      studied. In all of them plasmatic levels of B Gonadotrophin were measured. The
      curetting material was fixed and studied on frozen sections and on paraffin
      embedded tissue. A high positive relationship between frozen and embedded
      material was observed. The sensibility, specificity, positive and negative
      predictive value of the frozen section to detect chorionic villi were 90.6; 100;
      100 and 74% for each of them.

PMID- 8525036
TI  - [Malignant melanoma in an ovarian dermoid cyst].
AB  - A case of patient that during a cesarean section, a dark zone of the Omentum was
      biopsied, and informated as melanosis. Then appeared a cystic mass in the left
      ovary, and an ooforectomy was performed, resulting a Primary Malignant melanoma.

PMID- 8525037
TI  - [Placental site trophoblastic tumor].
AB  - A clinical case of placental site trophoblastic tumor, is presented in a patient
      of 27 years old. Diagnosis, clinical behavior and treatment are emphasized in
      this very infrequent pathology.

PMID- 8525038
TI  - [Bacterial vaginosis. I: history, microbiology, and diagnosis].

PMID- 8525039
TI  - [Active labour management in primiparas. Prospective study].
AB  - The objective of our study was prospectively compare the effect in the rate of
      cesarean section of active labor management and of traditional labor management
      in primiparas with physiological term pregnancy. From september 1, 1993 to may
      31, 1994, 145 primiparas with physiological term pregnancy were randomly assigned
      to one group of active labor management (study group, n = 75) and to one group of
      traditional labor management (control group, n = 70). Cesarean section rate was
      9.3% in the study group and 20% in the control group (p < 0.05). There was no
      increase in fetal morbidity or mortality. Active labor management can reduce
      cesarean section rate in primiparas with physiological term pregnancy.

PMID- 8525040
TI  - [Fetal growth retardation].

PMID- 8525041
TI  - CD28 and T-cell activation.

PMID- 8525042
TI  - CD28/CTLA-4 receptor structure, binding stoichiometry and aggregation during T
      cell activation.

PMID- 8525043
TI  - The critical role of CD28 signalling in the prevention of human T-cell anergy.

PMID- 8525044
TI  - Mechanisms of CD28 signalling.

PMID- 8525045
TI  - Signalling intermediates of CD28.

PMID- 8525046
TI  - Regulation of IL2 gene transcription via the T-cell accessory molecule CD28.

PMID- 8525047
TI  - CD28 costimulation regulates long-term expression of the three genes (alpha,
      beta, gamma) encoding the high-affinity IL2 receptor.

PMID- 8525048
TI  - The role of CD28 in the activation of T lymphocytes to proliferate in response to
      IL4.

PMID- 8525049
TI  - T-cell costimulation via CD28-CD80/CD86 and CD40-CD40 ligand interactions.

PMID- 8525051
TI  - Lymphocyte costimulation: multiple pathways, multiple functions?

PMID- 8525050
TI  - Blocking CD28/B7 with soluble competitors: immunological phenotype of mCTLA4-H
      gamma 1 transgenic mice.

PMID- 8525052
TI  - CD80 (B7-1) and CD86 (B7-2): potential targets for immunotherapy?

PMID- 8525053
TI  - Mutations which result in constitutive expression of the Bordetella pertussis
      filamentous haemagglutinin gene.
AB  - The expression of the filamentous haemagglutinin (FhaB) of Bordetella pertussis
      is positively regulated by the bvg locus which encodes a transcriptional
      activator, BvgA, and a transmembrane sensor protein, BvgS. The gene encoding
      FhaB, fhaB alone, is not expressed in Escherichia coli, but the introduction of
      the bvg locus in trans can restore fhaB expression. Using fhaB::lacZY fusions, we
      have isolated, in E. coli, partially bvg-independent constitutive mutants. The
      corresponding mutations have been localized to the upstream region of the fhaB
      promoter at position -15, -16 and -42 from the transcription initiation site. In
      the absence of the bvg locus, the strength of the mutated promoters was 15 and
      200 times higher than the wild-type promoter in the absence of the bvg locus. The
      expression of these mutated promoters was still enhanced by the presence of the
      bvg locus.

PMID- 8525054
TI  - Characterization of the gor gene of the lactic acid bacterium Streptococcus
      thermophilus CNRZ368.
AB  - Cloning and characterization of the gor gene of the lactic acid bacterium
      Streptococcus thermophilus, encoding glutathione reductase, are described in this
      paper. This enzyme is a part of the enzymatic defences against oxidative stress
      in eukaryotic cells and in Gram-negative bacteria, but was never found in Gram
      positive bacteria before this study. The amino acid sequence shares extensive
      similarities with glutathione reductases from other organisms, e.g. 62% amino
      acid identity with Escherichia coli protein. Northern blot analysis and
      glutathione reductase enzyme assays gave evidence that the gene is expressed in
      aerobically growing cells.

PMID- 8525055
TI  - Phylogenetic analysis of the genus Rickettsia by 16S rDNA sequencing.
AB  - Rickettsiae are Gram-negative bacteria which multiply only inside host cells and
      need arthropods either as reservoirs or as vectors. Using the polymerase chain
      reaction and an automated laser fluorescent DNA sequencer, we amplified and
      sequenced the 16S rRNA (rDNA) of all available bacteria of the genus Rickettsia.
      R. tsutsugamushi remained close to the other bacteria of the genus Rickettsia
      using this technique, contrary to previous conclusions based on the study of the
      Sta-58 protein antigen. We found that R. canada was not included in the typhus
      group, as is currently recognized, but was grouped with the rickettsiae of the
      spotted fever group (SFG). All the SFG rickettsiae tested were grouped in the
      same cluster (R. conorii, Indian tick typhus rickettsia, Astrakhan fever
      rickettsia, Israeli tick typhus rickettsia, HA-91, R. sibirica, R. parkeri, "R.
      africae", "R. slovaca", R. rickettsii, Thai tick typhus rickettsia, R. japonica,
      R. massiliae, R. rhipicephali, R. montana, two recent isolates GS and Bar 29, R.
      australis, R. akari, R. bellii and R. helvetica). The recently described ELB
      bacterium, the agent of the Californian murine typhus, and AB bacterium, a
      bacterium associated with male killing in the ladybird beetle, were found in this
      cluster. The sequences of R. conorii Moroccan strain/Indian tick typhus
      rickettsia, R. massiliae/GS and R. sibirica/HA-91 were identical. All the
      rickettsiae had a unique ancestor with bacteria also isolated in arthropods
      (Ehrlichia, Cowdria, Anaplasma, Wolbachia pipientis), eventually pathogenic for
      mammals and implicated in parthenogenesis and cytoplasmic incompatibility. We
      conclude that a unique bacterium started a stable association with arthropod
      ancestors and generated the observed diversity of the currently isolated members
      of the Rickettsiales.

PMID- 8525056
TI  - Phylogenetic characterization of the ubiquitous electron transfer flavoprotein
      families ETF-alpha and ETF-beta.
AB  - Electron transfer flavoproteins (ETF) are alpha beta-heterodimers found in
      eukaryotic mitochondria and bacteria. We have identified currently sequenced
      protein members of the ETF-alpha and ETF-beta families. Members of these two
      families include (a) the ETF subunits of mammals and bacteria, (b) homologous
      pairs of proteins (FixB/FixA) that are essential for nitrogen fixation in some
      bacteria, and (c) a pair of carnitine-inducible proteins encoded by two open
      reading frames in Escherichia coli (YaaQ and YaaR). These three groups of
      proteins comprise three clusters on both the ETF-alpha and ETF-beta phylogenetic
      trees, separated from each other by comparable phylogenetic distances. This fact
      suggests that these two protein families evolved with similar overall rates of
      evolutionary divergence. Relative regions of sequence conservation are evaluated,
      and signature sequences for both families are derived.

PMID- 8525057
TI  - Identification and strain differentiation of Mycobacterium species on the basis
      of DNA 16S-23S spacer region polymorphism.
AB  - Amplification of the region separating the genes coding for the two rRNA species
      16S and 23S was performed to identify 56 mycobacterial strains, belonging to
      eleven species: Mycobacterium tuberculosis, M. avium, M. kansasii, M. gordonae,
      M. abscessus, M. fortuitum, M. xenopi, M. bovis, M. bovis/BCG, M. africanum and
      M. intracellulare. Reproducible amplification patterns were obtained with most
      species with the exception of M. kansasii which showed heterogeneity, confirming
      the existence of a genetically distinct subspecies within this species. In
      addition, we used the amplified products as target DNA for restriction
      endonuclease digestion and RAPD (randomly amplified polymorphic DNA) analysis to
      compare strains of M. abscessus, M. tuberculosis and M. avium. The discriminatory
      power of these two typing methods was higher than when whole genomic DNA is used
      as target. Our results demonstrate that the two-step approach to identification
      and typing on the basis of the hypervariability of 16S-23S spacer region is
      reliable, rapid and simple, and consequently could be an epidemiological tool in
      clinical laboratories.

PMID- 8525058
TI  - Two geographically distinct isolates of Borrelia burgdorferi from the United
      States share a common unique ancestor.
AB  - The genetic diversity of Borrelia burgdorferi isolates from several geographic
      regions was evaluated by nucleotide sequence analysis of the genes encoding 23S
      ribosomal RNA and outer surface protein A. Comparison of nucleotide sequences
      spanning 738 bp of the 23S ribosomal DNA from two unusual isolates, DN127 (Del
      Norte County, California) and 25015 (Millbrook, New York), to homologous
      sequences from other B. burgdorferi isolates from the United States and Russia
      identified several nucleotide sequence polymorphisms that are unique to these two
      isolates. Sequence analysis of a 615 nucleotide segment of the gene encoding
      outer surface protein A also revealed greater similarity of strains DN127 and
      25015 (94.1%) compared to other US and Eurasian isolates. These data were further
      corroborated by genomic macrorestriction analysis, in which DN127 and 25015
      demonstrated unique restriction digestion patterns. Our findings suggest that
      substantial genetic diversity of B. burgdorferi, rivaling that of European
      strains, exists among isolates from the United States. Strains DN127 and 25015
      are unique among all B. burgdorferi isolates tested to date, and though isolated
      from opposite longitudinal extremes of the North American continent, are closely
      related.

PMID- 8525059
TI  - CarRS of Azospirillum brasilense is homologous to a large family of aldehyde
      dehydrogenases rather than to two-component regulators.

PMID- 8525060
TI  - Are there biological functions for bacterial endo-N-acetyl-beta-D
      glucosaminidases?
AB  - The endo-N-acetyl-beta-D-glucosaminidases (ENGase) acting on the N-N'
      diacetylchitobiosyl core of N-glycosylproteins are essential reagents for the
      investigation of the structure and the functions of glycoproteins. These enzymes
      were largely studied with the aim of offering more tools with new and broader
      substrate specificities to the community of glycobiologist. Conversely, little
      attention was given to their potential role in the physiology of bacteria, even
      though it had been shown that ENGases are important enzymes for the physiology of
      animal and plant cells. In this brief review, we present the main characteristics
      of the bacterial ENGases and confine our discussion to biological aspects of
      their action in bacterial systems.

PMID- 8525061
TI  - Analysis of genes encoding the cell division protein FtsZ and a glutathione
      synthetase homologue in the cyanobacterium Anabaena sp. PCC 7120.
AB  - Heterocysts, cells specialized in nitrogen fixation in Anabaena sp. PCC 7120,
      lose the potential for cell division once fully differentiated. This suggests
      that cell division activity is differentially regulated in heterocysts and
      vegetative cells. FtsZ has been shown to play a crucial role in bacterial cell
      division. Two degenerate oligonucleotide primers were designed to detect, by
      polymerase chain reaction (PCR), an ftsZ homologue from the heterocystous
      cyanobacterium Anabaena sp. PCC 7120. A PCR-amplified DNA fragment was cloned and
      used as a probe to isolate the entire ftsZ gene of Anabaena sp. PCC 7120. The
      deduced amino acid sequence shares strong similarities with other FtsZ proteins,
      suggesting remarkable conservation of the FtsZ protein during evolution. An ORF
      downstream of ftsZ, which would be transcribed in the opposite direction compared
      to ftsZ, could encode a polypeptide with significant sequence similarity to the
      glutathione synthetase from Escherichia coli. Inactivation experiments in vivo
      for both ftsZ and the glutathione synthetase gene did not yield any double
      recombinants either in the presence or in the absence of combined nitrogen,
      suggesting that both genes are essential for cell growth under these conditions.

PMID- 8525062
TI  - Comparison of arbitrarily primed polymerase chain reaction and cell envelope
      protein electrophoresis for analysis of Acinetobacter baumannii and A. junii
      outbreaks.
AB  - Two successive Acinetobacter outbreaks in a neonatal intensive care unit were
      studied with arbitrarily primed polymerase chain reaction (AP-PCR), cell envelope
      protein electrophoresis (protein fingerprinting) and antibiotic susceptibility
      testing. AP-PCR fingerprinting and protein fingerprinting yielded identical
      clustering of the isolates studied. Susceptibility test results were useful for
      rapid recognition of the outbreaks, but clustering of several isolates was
      different from the clustering obtained with AP-PCR fingerprinting and protein
      fingerprinting. Typing results indicated that the two outbreaks, which occurred
      at a three-month interval, were each caused by a single strain, and that both
      strains differed from the strains prevailing in the hospital. The strain of one
      outbreak was identified as A. junii, a species commonly not involved in
      outbreaks. A. baumannii isolates collected from different departments of this
      hospital during a period of four years clustered into only five different types.
      Moreover, strains from different departments of a second hospital belonged to the
      type prevailing in the first hospital, although there were no apparent
      connections between the two institutions. This may indicate that only a limited
      number of strains of the A. calcoaceticus-baumannii complex are involved in
      nosocomial outbreaks.

PMID- 8525063
TI  - Nucleotide sequence and characterization of peb4A encoding an antigenic protein
      in Campylobacter jejuni.
AB  - The 29-kDa protein PEB4, a major antigen of Campylobacter jejuni, is present in
      all C. jejuni strains tested and elicits an antibody response in infected
      patients. By screening a lambda gt11 library of chromosomal DNA fragments of C.
      jejuni strain 81-176 in Escherichia coli Y1090 cells with antibody raised against
      purified PEB4, a recombinant phage with a 2-kb insert expressing an
      immunoreactive protein of 29 kDa was isolated. DNA sequence analysis revealed
      that the insert contains two complete open reading frames ORF-A and ORF-B. ORF-A
      (peb4A) encodes a 273-residue protein with a calculated molecular mass of 30,460
      daltons. The deduced amino acid sequence, composition and pl of the recombinant
      mature protein are similar to those determined for purified PEB4. The first 21
      residues resemble a signal peptide. Gene bank searches indicated 33.7% identity
      with protein export protein PrsA of Bacillus subtilis and 23.8% identity with
      protease maturation protein precursor PrtM of Lactococcus lactis. PCR experiments
      indicate that peb4A is highly conserved among C. jejuni strains. ORF-B begins 2
      bp after the last codon of peb4A and encodes a putative protein of 353 residues
      with 63.4% identity with E. coli fructose 1,6-biphosphate aldolase. The sequence
      arrangement suggests that these two genes form an operon.

PMID- 8525064
TI  - Bacteriocin 28b, a chromosomally encoded bacteriocin produced by most Serratia
      marcescens biotypes.
AB  - Twenty-six Serratia marcescens strains belonging to fifteen different biotypes
      were found to produce bacteriocins active against Escherichia coli. On the basis
      of the pattern of bacteriocin sensitivity of E. coli mutant strains,
      immunological assays and Southern blot hybridization with a probe for the S.
      marcescens bss (bacteriocin 28b structural) gene, it was concluded that all these
      strains apparently produce chromosomally encoded bacteriocins related to
      bacteriocin 28b. To confirm this conclusion, the genes encoding the bacteriocin
      produced by one of these strains (S. marcescens JF246) were cloned in plasmid
      pBR328. E. coli harbouring recombinant plasmid pDG301 produced a bacteriocin
      active against E. coli and immunologically related to bacteriocin 28b.
      Immunoblotting experiments showed that bacteriocins 28b and L appear to have the
      same apparent molecular mass (45 kDa). Furthermore, recombinant plasmid pDG301
      DNA hybridized with a bss gene probe.

PMID- 8525065
TI  - Utilization of cellobiose and other beta-D-glucosides in Agrobacterium
      tumefaciens.
AB  - Agrobacterium tumefaciens strain C58 was able to utilize carbon from cellobiose
      and some other beta-D-glucosides as efficiently as from glucose. beta-D-glucoside
      utilization was partially inducible and the induction was subject to catabolite
      repression by glucose, independently of the presence of cyclic AMP in the medium.
      It was also independent of Ti plasmid-encoded functions. beta-D-glucosides were
      hydrolysed by a single, cytoplasmic and constitutively expressed beta
      glucosidase, which was active on non-phosphorylated substrates and insensitive to
      glucose inhibition.

PMID- 8525066
TI  - Prophage distribution in coryneform bacteria.
AB  - Four temperate bacteriophages of corynebacteria were isolated after UV induction.
      Phages phi 304L and phi 304S were both induced from Corynebacterium glutamicum
      ATCC 13058, ATCC 21488, ATCC 21649 and ATCC 21650 strains, and have no known
      sensitive host. Phages phi 15 and phi 16 were both induced from ATCC 14020 and
      ATCC 21792. Phage phi 15 formed turbid plaques on Corynebacterium sp. ATCC 21857
      and on C. glutamicum ATCC 13058, ATCC 21488, ATCC 21649 and ATCC 21650. Phage phi
      16 produced turbid plaques only on C. glutamicum ATCC 21792 cured of prophage phi
      16. All these phages belong to the Siphoviridae family. Their genomes consist of
      a double-stranded DNA with cohesive ends and share no homology with each other.
      Prophages phi 16, phi 304L and phi 304S were integrated into their respective
      host chromosomes, whereas prophage phi 15 seemed to persist free in the cell.
      Cross-hybridizations between phage DNAs and total cellular DNA obtained from 20
      strains belonging to the genera Corynebacterium and Brevibacterium did not show
      the presence of these prophages in strains other than their respective hosts.

PMID- 8525067
TI  - Immunological response in mice after long-term stimulation with cell wall
      antigens from Brucella melitensis.
AB  - The continuous stimulation of the immune system using cell wall antigens from
      Brucella melitensis was found to cause both quantitative and qualitative changes
      in circulating lymphocyte populations in mice. Animals were inoculated in the
      hind legs with antigens on alternate days for varying lengths of time. During a
      two-month period, we saw a higher number of circulating lymphocytes, with an
      increase in the number of CD4+ cells (L3T4+) and B lymphocytes (I-Ad). After two
      months, a drop in the overall number of circulating lymphocytes occurred, with a
      decrease in CD4+ cells and an increase in CD8+ cells. During the first two
      months, we observed a size increase in popliteal lymph nodes and an elevated
      humoral response. The response then waned with the declining CD4+ cells. In the
      first two months, the treated animals also showed an in vitro response to two
      mitogens, concanavalin A and lipopolysaccharide and to the cell wall fraction,
      after which the treated animals showed a decreased response.

PMID- 8525068
TI  - Electrical properties of extracted rat liver tissue.
AB  - We attempted to investigate the process of ischemia-induced disturbances in the
      rat liver, employing the electrical bio-impedance technique. The electrical bio
      impedance was measured continuously over 6 h by the 4-electrode method, at
      various incubation temperatures, in six liver samples extracted from male Wistar
      rats. The electrical properties of biological tissues can be expressed in terms
      of three parameters: extracellular resistance (Re), intracellular resistance (Ri)
      and cell membrane capacitance (Cm). These three parameters were calculated from
      the measured values of the electrical impedance by the curve-fitting technique,
      using a computer program. The Re value increased rapidly after the rat livers
      were extracted, and then decreased slowly. The Re value reached a peak after
      about 13 min at 36 degrees C, and then decreased slowly, becoming constant after
      3 h. There was a negative correlation between the Tmax of Re (the time when Re
      reached a maximum) and the incubation temperature (R = -0.973, P < 0.001). The Ri
      value decreased once in the early stage after extraction, followed by almost no
      change and then an increase after 4 h at 36 degrees C. The Cm showed a similar
      pattern of change to the Re value, and a negative correlation was also found
      between the Tmax of Cm and the incubation temperature (R = -0.969, P < 0.001).
      The increase in the Re and Cm values, and the decrease in the Ri value for quite
      long periods after the blood flow has stopped, suggest an increase in the
      resistance of extracellular fluid due to a decrease in its volume, an increase in
      cell membrane capacitance due to cell swelling, and a decrease in cellular fluid
      resistance due to an increase in its volume. The time when the Cm value decreases
      rapidly after an initial gradual decrease after the peak corresponds well with
      the time when the Ri value begins to increase, from which it is estimated that
      cell lysis proceeds and that the flow of extracellular fluid into the cell begins
      at this time. The findings of this study suggest the possibility of estimating
      the changes in liver tissue or the tissue structure due to ischemia.

PMID- 8525069
TI  - Glutathione in plasma, liver, and kidney in the development of CCl4-induced
      cirrhosis of the rat.
AB  - Plasma glutathione is markedly decreased in human cirrhosis of the liver. This
      decrease is said to be caused by reduced concentrations of liver glutathione.
      However, several studies on hepatic glutathione have revealed its concentrations
      to be unchanged, decreased, or even elevated. To test these inconsistencies we
      investigated the glutathione status of plasma, liver, and kidney in rats
      chronically exposed to carbon tetrachloride (CCl4). After 14 weeks of CCl4
      treatment, histological examination revealed progressive cirrhotic
      transformation. After 20 weeks, complete micro-nodular cirrhosis was present and
      distinct ascites had developed. Plasma reduced glutathione (GSH) decreased by 34%
      in the early and by 44% in the late group, paralleled by a 65% and 76% decrease
      of plasma oxidized glutathione (GSSG). Liver GSH in early stages of cirrhosis was
      reduced by 49%, but in late cirrhosis it did not differ from controls. In
      contrast, liver GSSG increased by 35% in the early and by 191% in the late group.
      Kidney GSH increased by 14% in early and 44% in late stage cirrhosis. Kidney GSSG
      was unchanged in the early group, but increased by 18% in the late group. The
      decrease of plasma GSH and GSSG is closely related to the severity of
      experimental cirrhosis and inversely related to an increase of hepatic oxidized
      glutathione. The hepatic content of reduced glutathione, however, is decreased in
      early cirrhosis only. According to these results the inconsistent findings in man
      could be due to differences in the stages of cirrhosis in the patients. The
      increase in kidney glutathione is a new finding that needs further investigation,
      but it may probably be related to kidney dysfunction in liver disease.

PMID- 8525070
TI  - Liver regeneration following partial hepatectomy and stimulation by hepatic
      stimulatory substance in cirrhotic and non-cirrhotic rats.
AB  - The effects of hepatic stimulatory substance (HSS) on cirrhotic and non-cirrhotic
      rats were studied after 70% partial hepatectomy. Liver cirrhosis was produced by
      weekly intragastric infusion of chloroform for 12-16 weeks. The HSS was prepared
      by extraction from the livers of weanling mice. Rats in the experimental group
      were injected with 5 ml HSS after 70% partial hepatectomy, and those in the
      control group received normal saline. The results showed that the 3H-thymidine
      incorporation was higher in the HSS group 24 h after partial hepatectomy in both
      cirrhotic and non-cirrhotic rats, and persistently higher in the non-cirrhotic
      rats at 48 h. Total DNA was significantly higher in the HSS group of non
      cirrhotic rats 24 and 48 h after partial hepatectomy. The restituted liver volume
      and weight was significantly higher in non-cirrhotic rats 48 h after partial
      hepatectomy, while there was no significant difference between the HSS and the
      control groups in the cirrhotic rats. The HSS induced significant effects on 3H
      thymidine incorporation in the non-cirrhotic liver, resulting in increasing liver
      weight, volume and total DNA 48 h after partial hepatectomy. In cirrhotic rats,
      the 3H-thymidine incorporation was higher in the HSS group at 24 h after partial
      hepatectomy, though not showing any increase at 48 h, but the regeneration of
      liver weight, volume and total DNA at 48 h showed no difference between the HSS
      group and the control group.

PMID- 8525071
TI  - Prevention of experimental hepatic metastasis with thromboxane synthase
      inhibitor.
AB  - To investigate the effectiveness of thromboxane (Tx) synthase inhibitor in the
      prevention of experimental hepatic metastasis, an in vivo study was designed.
      Hepatic metastasis was brought about by injection of 1 x 10(5) cells of colon 38
      tumor into the portal vein of C57 B1/65 mice. Seven groups (n = 16 in each group)
      received different treatments: with TxA2 synthase inhibitor (sodium ozagrel), 5,
      10 or 15 mg/kg BW before tumor inoculation, and daily for the following 3 days,
      (groups A, B and C, respectively); with acetyl salicylic acid (aspirin), 1.0, 1.5
      or 2.0 mg/kg BW (groups C, D, and E, respectively); a control group, inoculated
      with vehicle only. Serum TxB2, a stable metabolite of TxA2, and prostaglandin F1
      alpha were measured. Labeling index for tumor proliferation by bromodeoxy-uridine
      radioimmuno-assay was also studied. Incidence of metastasis in groups A (60.5%),
      B (49.5%), C (43.0%), D (80.5%), E (66.0%) and F (58.4%) was less than that in
      the control group (100%). Tumor size, number of labeling index did not differ
      among the groups. Serum TxB2 (pg/ml) levels were significantly lower in all of
      the groups than in the control. Serum PGF1 alpha levels in the groups with
      aspirin were lower than those in sodium ozagrel. Tx synthase inhibitor is
      effective in the prevention of experimental hepatic metastasis when it is given
      before and immediately after tumor inoculation. As Tx synthase inhibitor leaves
      metabolic pathway to PGI2 production intact, it is more effective in the
      prevention of metastasis than aspirin since aspirin inhibits both thromboxane and
      PGI2.

PMID- 8525072
TI  - Treatment of patients with severe head injury by triamcinolone: a prospective,
      controlled multicenter clinical trial of 396 cases.
AB  - The present studies were conducted to test whether the outcome of severe head
      injury is improved by early administration of the synthetic corticosteroid
      triamcinolone. In a prospective, double-blind, multicenter clinical trial, 396
      patients with severe head injury were randomized to a steroid group (n = 187)
      receiving 200 mg triamcinolone acetonide (Volon A soluble) i.v. within 4 h after
      trauma, followed by 3 x 40 mg/day i.v. for 4 days, and 3 x 20 mg/day i.v. for a
      further 4 days, and a placebo group (n = 209) receiving injections which did not
      contain any active drug. The placebo group was subjected to the same standard
      treatment procedures. Clinical features were not different between the groups
      upon admission to hospital. Subdural hematoma, epidural hematoma, and focal
      supratentorial contusion were among the most frequent diagnoses. The result of
      treatment with triamcinolone was assessed at discharge from the hospital and at 1
      year after trauma, using the Glasgow Outcome Scale. Differences in favor of
      steroid treatment could be detected with regard to the patients' condition at
      discharge (P = 0.0634). More patients with steroids had a good recovery (49.2% vs
      40.7%), and fewer died (16.0% vs 21.5%). Differences in outcome were even more
      pronounced (P < 0.0145) in patients with a focal lesion and a Glasgow Coma Score
      on admission of < 8 (n = 93). In this group, 34.8% of the patients made a good
      recovery, as against 21.3% of the placebo group; mortality was also lower in the
      verum group (19.6% vs 38.3%). The results indicate that a major subgroup of
      patients with severe head injury benefits from early administration of
      triamcinolone. Efficacy of the treatment can be expected, in particular, in
      patients with a focal cerebral lesion and a Glasgow Coma Score of < 8 on
      admission. Administration of steroids beginning at the scene of an accident would
      therefore be beneficial in these cases.

PMID- 8525073
TI  - The effect of methylprednisolone on cisplatin-induced nephrotoxicity in rat renal
      cortical slices.
AB  - To investigate the protective action of methylprednisolone against cisplatin
      nephrotoxicity, the effect of in vivo pretreatment with methylprednisolone on the
      cisplatin-induced reduction in p-aminohippurate (PAH) accumulation and
      gluconeogenesis was examined using renal cortical slices prepared from Sprague
      Dawley rats. The PAH accumulation in the kidney slices prepared from
      methylprednisolone-pretreated rats was significantly reduced following in vitro
      incubation with 2 mM cisplatin, to a degree equal to that observed in the slices
      prepared from untreated rats. However, the inhibitory effect of cisplatin on
      gluconeogenesis in the renal cortical slices obtained from methylprednisolone
      pretreated rats was significantly smaller than that seen in the slices from
      untreated rats. Our present studies suggest that in vivo pretreatment with
      methylprednisolone may contribute to its protective effect against cisplatin
      nephrotoxicity through the process of gluconeogenesis in renal epithelial cells.

PMID- 8525074
TI  - Influence of dietary amiloride supplement on the zinc status of growing rats with
      marginal zinc supply.
AB  - We divided 36 male pathogen-free Sprague-Dawley rats with an average live mass
      (LM) of 51 g into four treatment groups of nine animals each. They received for a
      period of 28 trial days a semisynthetic purified diet based on casein for ad
      libitum consumption, supplemented with 5 ppm zinc (groups 1-3) or 57 ppm zinc
      (group 4) as zinc sulfate. In addition to the diet, groups 2 and 3 were given a
      diuretic supplement of amiloride at the therapeutic dose rate (0.4 mg
      amiloride/kg LM0.75 per day) or in a dosage corresponding to the chronic toxicity
      level (maximum tolerated dose; 0.8 mg amiloride/kg LM0.75 per day). The
      supplementation with amiloride, acting as a potential Zn-binding ligand at the
      selected dosage levels, had no influence on the animals' live weight during the
      28-day trial period; weight gain was determined solely by the dietary Zn
      concentration. Amiloride administered at the therapeutic or the maximum tolerated
      dose produced no evidence of a diminished Zn status in terms of the alkaline
      phosphatase activity in the serum or the Zn concentration in the serum, femur and
      testes. Medication with amiloride at the maximum tolerated dose even exerted a
      positive effect on the zinc supply status as demonstrated by the raised Zn
      concentration in the serum. This suggests that zinc supplementation may not be
      required during medication with amiloride in human medicine.

PMID- 8525075
TI  - Influence of thyrotropin-releasing hormone on experimental pancreatitis in rats.
AB  - The main purpose of this study was to investigate the influence of thyroid
      releasing hormone on acute sodium-taurocholate-induced pancreatitis in rats.
      Thyroid-releasing hormone did not change the survival rate, serum amylase,
      glucose calcium, liver transaminases levels or the degree of pancreatic damage,
      but reduced lactate dehydrogenase. Our findings suggest that the use of thyroid
      releasing hormone has no beneficial effect on the course of acute experimental
      pancreatitis.

PMID- 8525076
TI  - Experimental megaileum.
AB  - Typical megaileum occurred in young male Wistar rats three months after ileum
      myenteric plexus denervation. An average of 58.4% denervation of the Auerbach
      plexus was obtained by serosal application of benzalkonium chloride (0.2% v/v).
      Denervation was assessed by ganglion cell counts in an 8 nm ring-shaped
      histological sectfrom the midportion of the treated segment. A morphometric study
      showed that the increased thickness of the megaileum wall was due to muscle
      hypertrophy and mucosal hyperplasia. The potential usefulness of this model of
      megaileum is emphasized.

PMID- 8525077
TI  - Phenotypical characterisation of intestinal spirochaetes isolated from pigs.
AB  - A combined evaluation of the phenotypical properties of five Serpulina type or
      reference strains and 163 Swedish isolates of spirochaetes from pigs and two from
      birds was made. The porcine isolates were collected from herds with a history of
      dysentery or severe diarrhoea and from herds chosen at random. On the basis of
      beta-haemolysis, indole production, hippurate hydrolysis, and alpha
      galactosidase, alpha-glucosidase and beta-glucosidase activity, the isolates
      could be divided into four main groups, I to IV, with three subgroups in group
      III. Group I included the type strain for Serpulina hyodysenteriae (B78). Group
      II was differentiated from group I only by weak beta-haemolysis. Group III
      included the type strain for Serpulina innocens (B256). Group IV included the
      pathogenic, weakly haemolytic strain P43. Group IV-spirochaetes were
      characterised by their ability to hydrolyse hippurate and by their lack of beta
      glucosidase activity. Group I and II-spirochaetes were isolated only from
      dysenteric or diarrhoeic pigs. There was a statistical relationship between pigs
      with diarrhoea and the isolation of group IV spirochaetes but no relationship
      with group III spirochaetes.

PMID- 8525078
TI  - Protection of cattle from bovine tuberculosis by vaccination with BCG by the
      respiratory or subcutaneous route, but not by vaccination with killed
      Mycobacterium vaccae.
AB  - Groups of cattle were vaccinated either with BCG Pasteur by the intratracheal or
      subcutaneous route or with killed Mycobacterium vaccae by the intradermal route
      and challenged intratracheally 54 days later with Mycobacterium bovis.
      Vaccination with BCG resulted in fewer animals developing tuberculous lesions and
      in a reduction in the number of lesions in the diseased animals compared with the
      unvaccinated group and the group vaccinated with M vaccae. None of the nine
      animals vaccinated intratracheally with BCG developed any tuberculous lung
      lesions after challenge with M bovis, but two of the nine animals from each of
      the groups dosed subcutaneously with low and medium doses of BCG developed lung
      lesions. There was little difference in protection against the M bovis challenge
      between the animals receiving the low dose (10(3) colony forming units, cfu) or
      medium dose (10(5) cfu) of subcutaneous BCG, but the medium dose of BCG produced
      stronger cell-mediated immune responses to bovine purified protein derivative
      (PPD) after vaccination. Vaccination intradermally with 10(9) heat-killed M
      vaccae did not protect cattle against an experimental challenge with M bovis and
      induced only weak cell-mediated immune responses to bovine PPD.

PMID- 8525079
TI  - Total intravenous anaesthesia in ponies using detomidine, ketamine and
      guaiphenesin: pharmacokinetics, cardiopulmonary and endocrine effects.
AB  - Pharmacokinetics and some pharmacological effects of anaesthesia induced by a
      combination of detomidine, ketamine and guaiphenesin were investigated in eight
      ponies. Cardiopulmonary function was studied and plasma met-enkephalin,
      dynorphin, beta-endorphin, arginine vasopressin, adrenocorticotrophin, cortisol,
      11-deoxycortisol and catecholamine concentrations were measured. The combination
      produced slight cardiorespiratory depression, hyperglycaemia and a reduction in
      haematocrit. There were no changes in plasma opioids, pituitary peptides or
      catecholamines. Plasma cortisol concentration decreased and plasma 11
      deoxycortisol increased indicating a suppression of steroidogenesis. Steady state
      ketamine and guaiphenesin concentrations were attained during the infusion
      period, and ketamine concentrations likely to provide adequate analgesia for
      surgical operations were achieved (more than 2.2 micrograms ml-1). Steady state
      detomidine concentration was not attained. The ponies took on average 68 minutes
      to recover to standing and the recovery was uneventful.

PMID- 8525080
TI  - Effect of dietary protein supplementation on the development of immunity to
      Ostertagia circumcincta in growing lambs.
AB  - Thirty four-and-a-half-month-old worm-free lambs were used to determine whether
      the rate of development of immunity to Ostertagia circumcincta infection in
      growing lambs could be influenced by the addition of a by-pass protein
      supplement. Sixteen lambs (groups 1 and 2) were fitted with an abomasal catheter
      and infected daily with 2000 O circumcincta L3 for eight weeks. Group 1 lambs
      received 45 g of crude protein day-1 (sodium caseinate) as a continuous infusion
      into the abomasum from week-1 to week 8. At week 9, groups 1 and 2, together with
      eight naive controls (group 3), were treated with anthelmintic and challenged one
      week later with 50,000 O circumcincta L3 and killed after a further 10 days. An
      additional six worm-free lambs provided feed intake and growth rate data. All the
      lambs were offered a complete ruminant ration (167 g crude protein kg-1) ad
      libitum. The cumulative liveweight gain of both the trickle-infected groups was
      less than that of the controls. The mean faecal egg counts were lower in group 1
      from day 39 after infection and the mean worm burdens were significantly lower
      than in group 2. Total Ostertagia populations did not differ significantly
      between group 3 and either group 1 or 2 lambs. Early L4 stages constituted a
      greater percentage of the total worm population in group 1 (79.5) and group 2
      (48.5) than in the challenge controls (group 3) (20.4). The trickle-infected
      lambs also had higher concentrations of gastric mast cell protease which
      correlated positively with the proportion of early L4 stages and negatively with
      the total worm burden. The provision of by-pass protein supplement accelerated
      the development of immunity to O circumcincta in these lambs.

PMID- 8525081
TI  - Creatine kinase isoenzyme profiles in the plasma of the domestic fowl (Gallus
      domesticus): effects of acute heat stress.
AB  - Creatine kinase isoenzyme activities in extracts of plasma, skeletal muscle,
      heart and brain tissue of domestic fowls were separated by anion exchange
      chromatography and tissue specific distributions of the isoenzyme designated MM
      CK, BB-CK1 and BB-CK2 were demonstrated. The muscle isoenzyme (MM-CK) was the
      predominant form in plasma (99 per cent) and its activity increased in response
      to an episode of acute heat stress.

PMID- 8525082
TI  - Post natal development of canine caudal cervical vertebrae.
AB  - The morphology and post natal ossification of the fifth, sixth and seventh
      cervical vertebrae of 51 crossbred puppies (aged from birth to 12 weeks) were
      examined grossly, histologically and radiographically. At birth there were two
      centres of ossification, one in the vertebral body and one in the base of each
      pedicle of the neural arch. By one month of age secondary centres of ossification
      were present in the cranial and caudal epiphyses of the vertebral body. By two
      months of age these epiphyseal centres began to show signs of closure.
      Endochondral ossification of the neural arch occurred from a single centre of
      ossification within each pedicle with bony fusion of the laminae occurring by one
      month of age. In addition the dimensions of the neural canal were measured. The
      difference between the caudal and cranial sagittal diameters of each vertebra was
      1 mm or less. It was concluded that, after one month of age, the shape of the
      neural canal can be influenced only by changes within the physes between the
      vertebral body and the neural arch or by the remodelling of bone formed by
      intramembranous ossification.

PMID- 8525083
TI  - Inhibition by dexamethasone of interleukin-1 beta and interleukin-6 expression in
      alveolar macrophages from cows.
AB  - The suppression by the synthetic glucocorticoid dexamethasone of the expression
      of interleukin-1 beta and interleukin-6 was examined in alveolar macrophages from
      cows. The expression of interleukin-1 beta mRNA was inhibited by treatment with
      dexamethasone for 16 hours in a dose-dependent fashion. The values of the
      concentration causing 50 per cent inhibition were in the range of 10(-9) to 10(
      8) M. Dexamethasone similarly inhibited the expression of interleukin-6 mRNA by
      50 per cent at a concentration of approximately 10(-8) M. In the concentration
      range from 10(-12) to 10(-4) M, dexamethasone had no effect on the expression of
      beta-actin. These results suggested that glucocorticoids may be involved in the
      regulation of the expression of interleukin-1 beta and interleukin-6 by the
      alveolar macrophages of cows.

PMID- 8525084
TI  - Expression and quantification of IgG and IgM molecules on the surface of
      lymphocytes of cattle infected with bovine leukaemia virus.
AB  - Immunogold-labelled antibodies were used with scanning electron microscopy (SEM)
      and fluorescent-labelled antibodies were used with flow cytometry (FACS) to
      evaluate the expression and quantity of IgG and IgM molecules on the surface of
      the lymphocytes of cattle infected with bovine leukaemia virus (BLV). The BLV
      infected animals were divided serologically and haematologically into groups with
      (BLV+PL+) and without (BLV+PL-) persistent lymphocytosis (PL). The percentage of
      IgM-bearing cells was significantly higher in the BLV+PL+ group than in the BLV
      PL- and BLV+PL- groups by FACS. There was a significantly higher percentage of
      IgG-bearing cells in the BLV+PL+ group than in the BLV-PL- and BLV+PL- groups by
      SEM, but no differences were found by FACS. A significantly higher intensity of
      IgM expression was observed in the BLV+PL+ group by SEM. A higher intensity of
      IgG expression in some animals was detected only by SEM. An increase in the
      number of larger IgM cells were observed in the BLV+PL- and BLV+PL+ groups by
      SEM. The SEM analysis was more sensitive than FACS in this experiment.

PMID- 8525085
TI  - Phylogeny of Serpulina based on sequence analyses of the 16S rRNA gene and
      comparison with a scheme involving biochemical classification.
AB  - Twenty-one putative Serpulina strains, representing six proposed biochemical
      groups, were selected for phylogenetic studies based on 16S rRNA sequencing. The
      biochemical groups were distinguished by the degree of beta-haemolysis, indole
      production, hippurate hydrolysis and alpha-galactosidase-, and beta-glucosidase
      activity. The 16S rRNA sequences of the U2 to U5 region, including three
      evolutionarily variable regions, from representatives of each biochemical group
      were determined by automated solid phase DNA sequencing after in vitro
      amplification by the polymerase chain reaction (PCR). The sequences generated
      were 532 nucleotides in length. Sequence alignments showed that all the strains
      were closely related, with six informative positions in the region sequenced. A
      dendrogram was constructed from these data and compared with the tentative
      biochemical classification. The results support the proposed biochemical
      classification and indicate that at least five genetic variants of the genus
      Serpulina can be identified.

PMID- 8525086
TI  - Effects of concanavalin A and pokeweed lectins on microvillar membrane proteins
      during the organ culture of rabbit intestinal mucosa.
AB  - The effects of pokeweed lectin (PWL) and concanavalin A (Con A) on microvillar
      membrane (MVM) proteins during the organ culture of rabbit ileal explants for 24
      hours were compared with the known effects of enteropathogenic Escherichia coli
      (EPEC). PWL resulted in the accelerated release of brush border enzymes into the
      culture medium, accompanied by decreased tissue activities and an increase in the
      total activity present in the tissue and culture medium. Con A had less effect on
      the release and tissue activities of brush border enzymes and the total activity
      was not increased. Sucrose density gradient centrifugation of the culture medium
      showed that MVM enzymes were predominantly particulate, consistent with their
      release as vesicles. Centrifugation of ileal explants showed that PWL, but not
      Con A, resulted in a decrease in the modal density of the brush border which was
      consistent with a lower glycoprotein-to-lipid ratio. These findings suggest that
      PWL, in common with EPEC, may cause the disruption and vesiculation of microvilli
      and the compensatory stimulation of MVM protein synthesis.

PMID- 8525087
TI  - Systemic and local gut-specific antibody responses in preruminant calves
      sensitive to soya.
AB  - The systemic and local (gut) patterns of antibodies against various proteins from
      soyabean were analysed in preruminant calves fed milk substitutes based on skim
      milk powder (SMP) or heated soyabean flour (HSF) as the main protein sources. The
      titres of IgM, IgA, IgG1 and IgG2 antibodies were determined against feed
      extracts and purified soyabean proteins by dot-blotting in plasma after three
      months and jejunal mucous secretions after six months of feeding the experimental
      diets. The calves fed HSF had higher levels of circulating IgA, IgG1 and IgG2
      antibodies against raw or heated soya extracts and purified proteins including
      alpha-conglycinin, beta-conglycinin, Bowman-Birk protease inhibitors and lectins
      than the calves fed SMP. In contrast, the differences between the IgM titres of
      the groups were most often not significant. The patterns of specific antibodies
      present in the jejunum were broadly similar to those observed in the blood,
      although the differences between the groups of calves more often reached
      significance for IgG2 and IgM than for IgA and IgG1, when the purified soyabean
      proteins were considered.

PMID- 8525088
TI  - Loss of chromosome B2-material in three cases of feline mammary tumours.
AB  - Tumour cells in three cases of mammary gland neoplasms in cats were analysed
      cytogenetically. There was a loss of chromosome B2-material in all the cases, and
      a loss of chromosome E3-material in two of them.

PMID- 8525089
TI  - Predictive value of foal kinematics for the locomotor performance of adult
      horses.
AB  - The gait of 24 horses was recorded on a treadmill when they were trotting at 4 m
      sec-1, first when they were four months old and again when they were 26 months.
      The data recorded at four months were used to predict the locomotion of the adult
      horses, and the predictions were assessed against the data recorded at 26 months.
      The locomotion of the foals and the adults appeared to be closely related, when
      the differences in segment length and joint angles due to growth were taken into
      account. The duration of swing, the total range of protraction and retraction,
      and the maximum tarsal flexion could be used to predict adult locomotion, because
      they correlated very well between the foals and adults. The durations of stance
      and stride in the foals had to be linearly and dynamically scaled to the height
      at the withers to become predictive for the adult values. The duration of swing,
      and the total range of protraction and retraction and the maximum tarsal flexion
      are also indicators of the quality of gait and as a result studies of foal
      kinematics can be used objectively to predict the locomotor performance of adult
      horses.

PMID- 8525090
TI  - Identification of native foot-and-mouth disease virus non-structural protein 2C
      as a serological indicator to differentiate infected from vaccinated livestock.
AB  - Cattle and pigs which have been vaccinated against foot-and-mouth disease can be
      distinguished from convalescent animals by radio-immunoprecipitation and sodium
      dodecyl sulphate polyacrylamide gel electrophoresis of the virus-induced proteins
      reacting with the respective sera. Baby hamster kidney cells infected with foot
      and-mouth disease virus (FMDV) (serotype A24) were labelled with 35S-methionine
      and the virus-induced proteins were precipitated with sera from vaccinated and
      subsequently challenged animals, convalescent animals retained for over 300 days,
      animals vaccinated or infected with viruses belonging to all serotypes of FMDV,
      and animals infected with encephalomyocarditis (EMC) or porcine or bovine
      enteroviruses. In addition to the structural proteins of the virus, the non
      structural proteins 2C, 3ABC, 3C, 3CD and 3D were precipitated by convalescent
      sera, but only 3D was precipitated by serum from vaccinated animals. Proteins L,
      2C and 3C were precipitated only after challenge with a heterotypic virus
      (serotype O1 Tunisia), indicating that virus replication of the challenge virus
      had taken place. No precipitation was detected with sera from EMC or enterovirus
      infected animals. The results indicate that protein 2C, and to a lesser extent
      the polypeptide 3ABC, could be used to differentiate potential carrier
      convalescent animals from vaccinated livestock.

PMID- 8525091
TI  - Detection of tetanus toxoid-specific memory T cells in equine lymph nodes but not
      in peripheral blood.
AB  - The use of tetanus toxoid as a recall antigen to investigate equine immune
      responses would be, in theory, a useful and cost-effective model in vitro.
      However, by using various regimens for culturing peripheral blood mononuclear
      cells from horses previously immunised with toxoid no proliferative response to
      the antigen was obtained in vitro, whereas lymph node mononuclear cells from the
      same animals proliferated significantly in response to it. The lack of response
      by the peripheral blood mononuclear cells was not due to the presence of a
      suppressive factor but to a lack of recognition of the antigen by the T cells of
      the peripheral blood.

PMID- 8525092
TI  - Effects of acute and chronic restraint on the adrenal gland weight and serum
      corticosterone concentration of mice and their faecal output of oocysts after
      infection with Eimeria apionodes.
AB  - Experiments were designed to investigate the potential stress of procedures
      commonly used for restraining mice and to discover whether habituation of the
      adrenocortical response occurred when chronic restraint was used. The study also
      examined the effect of chronic restraint on the faecal output of oocysts by mice
      trickle infected with Eimeria apionodes. The results showed that restraining mice
      for one hour was stressful and that restraining them repeatedly for one hour
      daily for seven or 21 days did not lead to habituation of the adrenocortical
      response. Restraint for one hour daily for seven days did not cause the
      recurrence of a clinical infection in mice which were chronically infected with E
      apionodes. Restraining mice for one hour daily for seven days before and for 14
      days during the infection also had no effect on the prepatency, patency or
      intensity of an E apionodes infection.

PMID- 8525093
TI  - Ultrastructural co-localisation of vimentin and cytokeratin in visceral
      glomerular epithelial cells of dogs with glomerulonephritis.
AB  - The expression of cytokeratin and vimentin was studied in the glomerular
      epithelial cells of canine kidneys with and without glomerular abnormalities.
      Using ultrastructural, immunogold single and double labelling techniques,
      cytokeratin and vimentin were found together in the visceral glomerular
      epithelial cells (vGECs) of abnormal kidneys. In normal kidneys, the vGECs
      expressed only vimentin, and cytokeratin was found exclusively in parietal
      glomerular epithelial cells (pGECs). These results confirm previous findings in
      the same animals, obtained by immunohistological staining techniques.

PMID- 8525094
TI  - Identification of leptospires of the Pomona and Grippotyphosa serogroups isolated
      from cattle in Zimbabwe.
AB  - Two strains of the genus Leptospira, isolated from kidneys of oxen slaughtered in
      Zimbabwe, one belonging to serogroup Pomona (strain SBF 8) and the other to
      serogroup Grippotyphosa (strain SBF 32), were identified by using cross
      agglutinin absorption, monoclonal antibody, restriction fragment length
      polymorphism and polymerase chain reaction analyses. The identification of the
      two strains was equivocal. Strain SBF 8 showed a close similarity to both
      serovars mozdok and proechimys by cross-agglutinin absorption tests and to
      serovar pomona by monoclonal antibody analysis, but had a distinct DNA
      restriction pattern. Strain SBF 32 showed a close antigenic similarity to
      serovars ratnapura, grippotyphosa and valbuzzi by the cross-agglutinin absorption
      test, and to serovar ratnapura by monoclonal antibody analysis but also had a
      distinct DNA restriction pattern. Both strains SBF 8 and SBF 32 reacted as
      members of species Leptospira kirschneri by the polymerase chain reaction. It is
      concluded that strains SBF 8 and SBF 32 represent new genetic strains in the
      Pomona and Grippotyphosa groups, respectively.

PMID- 8525095
TI  - Relationship between clinical manifestations of footrot and specific DNA products
      of Dichelobacter nodosus amplified through PCR.
AB  - A total of 141 Dichelobacter nodosus isolates from 46 merino sheep farms with
      various clinical forms of footrot was examined by the gelatin gel test and the
      polymerase chain reaction (PCR) using virulent (Vf2 and Vr2) and benign (Bf and
      Br) specific primers. Isolates from sheep with virulent and high intermediate
      footrot usually produced relatively thermostable proteases, but a decreasing
      proportion of the isolates from sheep with medium and low intermediate or benign
      footrot had thermostable proteases, as determined by the gelatin gel test. The
      amplification by PCR of a major band of 857 bp by Vf2 and Vr2 was often
      associated with isolates from the more virulent forms of footrot whereas the
      presence of a major band of 1300 bp by Vf2 and Vr2 and/or a band of 609 bp by Bf
      and Br was associated with isolates from less virulent forms of footrot.
      Nevertheless, the virulent and benign gene regions represented by Vf2 and Vr2 and
      Bf and Br are only two of the many factors involved in determining the virulence
      of D nodosus. As a result the relationship observed between the clinical
      manifestations of footrot and specific DNA products amplified by PCR was not
      complete.

PMID- 8525096
TI  - Protection of goats against rinderpest by vaccination with attenuated peste des
      petits ruminants virus.
AB  - The ability of the attenuated peste des petits ruminants vaccine virus to protect
      small ruminants against virulent rinderpest virus was investigated. Out of four
      susceptible goats that were infected with the highly virulent Saudi strain of
      rinderpest virus by intranasal ioculation, three developed mild clinical signs of
      disease and infected susceptible in-contact goats and cattle with rinderpest
      virus. However, four goats which had been vaccinated with the attenuated peste
      des petits ruminants virus resisted challenge with virulent rinderpest virus and
      did not infect susceptible in-contact animals.

PMID- 8525097
TI  - Investigations of a killed dermatophyte cell-wall vaccine against infection with
      Microsporum canis in cats.
AB  - A laboratory-prepared killed Microsporum canis cell-wall vaccine was evaluated
      under conditions simulating an accidental infection of a cattery, by inoculating
      eight- to nine-week-old cats with the vaccine or with a placebo control. The
      vaccinated cats developed high titres of anti-dermatophyte IgG as measured by an
      ELISA, and a small cell-mediated response against M canis as measured by a
      lymphocyte blastogenesis assay, using a whole fungus extract. After being
      inoculated the cats were challenged by the introduction of an infected cat into
      the same room. All the vaccinated and control cats became culture-positive for M
      canis within four weeks of the introduction of the infected cat. Four of the six
      control cats and all the vaccinated cats developed lesions consistent with
      dermatophytosis within 16 weeks after exposure to the infected cat.

PMID- 8525098
TI  - Expression of class II major histocompatibility complex molecules in renal
      tubular epithelial cells of canine kidneys affected with tubulointerstitial
      nephritis.
AB  - Class II major histocompatibility complex (MHC) products are important molecules
      on various antigen-presenting cells and induce a T cell-specific immune response.
      The distribution of class II MHC molecules in the normal canine kidneys of dogs
      with tubulointerstitial nephritis was investigated by using a sensitive
      immunocytochemical method. In the normal canine kidney, class II MHC molecules
      were detected in interstitial 'dendritic' cells. In cases of tubulointerstitial
      nephritis, however, the expression of class II MHC molecules extended to other
      renal elements such as the epithelial cells of cortical and medullary tubules
      and, in some cases, the endothelial cells of peritubular capillaries. The tubular
      expression of class II MHC molecules was enhanced in dogs with higher levels of
      proteinuria. The results suggest that heavy proteinuria may be one triggering
      factor in canine tubulointerstitial damage, probably mediated by the reabsorption
      of filtered cytokines and immunogenic peptides which induce tubular epithelial
      cells to behave as immune accessory cells.

PMID- 8525099
TI  - A simple method for measuring glomerular filtration rate in dogs.
AB  - A technique for measuring glomerular filtration rate (by six-sample plasma
      clearance) and extracellular fluid volume is described. The results obtained for
      glomerular filtration rat per extracellular fluid volume with a three blood
      sample technique are also presented. Concurrently with the blood sample
      techniques measuring plasma clearance, glomerular filtration rate per
      extracellular fluid volume was also measured using an external radiation detector
      and no blood samples. The validity of expressing glomerular filtration rate per
      extracellular fluid volume (rather than per body weight or surface area) and the
      clinical utility of the results obtained with the external radiation detector are
      discussed.

PMID- 8525100
TI  - Immunohistochemical evaluation of canine primary liver carcinomas: distribution
      of alpha-fetoprotein, carcinoembryonic antigen, keratins and vimentin.
AB  - The immunohistochemical expression of the oncofetal proteins alpha-fetoprotein
      (AFP) and carcinoembryonic antigen (CEA), and the intermediate filament proteins
      keratin and vimentin was analysed in 18 canine liver carcinomas. All the tumours
      other than hepatocellular carcinomas, with the exception of one poorly
      differentiated carcinoma, were AFP negative, and only cholangiocarcinomas and
      mixed (hepatocellular and cholangiocellular) carcinomas were CEA positive. All
      the histological types of tumours expressed high and low molecular weight
      keratins, and keratin and vimentin were both expressed in three tumours (one
      moderately differentiated hepatocellular carcinoma, one mixed carcinoma and one
      poorly differentiated carcinoma). The findings demonstrate the use of
      immunohistochemical staining methods for analysing the expression of some tumour
      markers in routinely processed tissue samples of canine liver carcinomas, and
      suggest that some of the tumour markers are correlated with histological types of
      tumour.

PMID- 8525101
TI  - Effects of the severity and duration of lesions on the primary and anamnestic
      humoral responses of sheep to Dichelobacter nodosus and observations of natural
      resistance to footrot.
AB  - In a flock of 137 sheep naturally infected with Dichelobacter nodosus the
      severity of the lesions was the principal factor associated with the humoral
      response early in the period of spread of D. nodosus, underrun lesions having the
      greatest effect. However, after five to six weeks, the duration of underrun
      lesions rather than their severity or number primarily influenced the response.
      Sheep first affected late in the period of spread had fewer affected feet, milder
      lesions and a lower humoral response than those affected earlier. An anamnestic
      humoral response was stimulated by injecting membrane-protein antigen of D
      nodosus subcutaneously 18 weeks after the sheep had been treated parenterally
      with antibiotics and antiseptic footbathing. The anamnestic response was related
      to the antibody level reached during the infection phase, and hence with the
      duration and severity of the lesions, and with the residual antibody level at the
      time of the anamnestic challenge, suggesting that the population of memory B
      cells specific for D nodosus was proportional to the size of the originally
      activated B cell population. Even after allowing for differences between the
      duration and severity of the lesions differential responses were detectable among
      the sheep. Primary and anamnestic responses of a non-specific nature occurred in
      control sheep.

PMID- 8525102
TI  - In vitro survival of the BS isolate of Chlamydia psittaci (ovis) in ruminal and
      abomasal contents.
AB  - The ability of the pathogenic BS isolate of Chlamydia psittaci (ovis) to survive
      after inoculation into ruminal or abomasal contents, and chlamydial transport
      medium held at 39 degrees C, was assessed by taking hourly samples which were
      cultured in mitomycin-treated McCoy cells. The chlamydiae survived for nine hours
      in the ruminal contents, eight hours in the abomasal contents and for 12 hours in
      transport medium, when the experiment was concluded. There was a steady decrease
      in the numbers of the organism in the ruminal and abomasal contents as their pH
      decreased, but the numbers in the transport medium also decreased without a
      corresponding change in pH. It is therefore possible that ewes may become
      infected with C psittaci (ovis) orally via the gastrointestinal tract.

PMID- 8525103
TI  - EHV-1-induced abortion in mice and its relationship to stage of gestation.
AB  - The most important consequence of equine herpesvirus-1 (EHV-1) infection is
      abortion. The object of the present study was to characteristic further a murine
      EHV-1 abortion model and to make comparisons with the natural host with
      particular reference to the stage of gestation during which the infection occurs.
      BALB/c mice at different stages of pregnancy were infected intranasally with EHV
      1 (strain AB4); they suffered respiratory distress, weight loss, and other
      constitutional signs of infection. When the virus was inoculated in the late
      second or early third week of gestation dead or dying fetuses were aborted,
      whereas infection between seven and nine days of pregnancy led to fetal death and
      resorption. During the process of resorption, complications were observed. Virus
      was frequently isolated from the placentas and occasionally from the tissues of
      the aborting fetuses, depending on the severity of the infection of the
      placentas. In some cases, therefore, the inoculation resulted in abortion
      although the infection was restricted to the placenta. Virus antigen was detected
      in the placentas, lungs and occasionally in other tissues of the aborting
      fetuses. The potential of this murine model for testing methods for the diagnosis
      and control of equine abortion is discussed.

PMID- 8525104
TI  - A pathological study of the perisinusoidal unit of the liver in acute African
      swine fever.
AB  - African swine fever is an acute haemorrhagic disease of pigs which may serve as a
      model for the study of the pathogenesis of other viral haemorrhagic fevers. This
      paper describes an ultrastructural study of the sequence of lesions produced in
      the perisinusoidal functional unit of the liver of pigs inoculated with the
      Malawi '83 strain of African swine fever virus, which is classified as
      haemadsorbing and highly virulent. Virus replication was observed in Kupffer
      cells and monocytes from three days after inoculation, in hepatocytes and fat
      storing cells at five and seven days after inoculation, and in sinusoidal
      endothelial cells at seven days after inoculation. Further observations included
      intravascular coagulation, which peaked at five days after inoculation, and
      fibroblast and myofibroblast transformation of fat-storing cells at seven days
      after inoculation. These results suggest that activated cells of the mononuclear
      phagocyte system may play a major role in this sequence of lesions and the
      possible role of the cytokines that may be released by these cells is discussed.

PMID- 8525105
TI  - Stability of von Willebrand factor and factor VIII in canine cryoprecipitate
      under various conditions of storage.
AB  - The stability of factor VIII and von Willebrand factor antigen in canine
      cryoprecipitate obtained from seven greyhound donors was determined after storage
      under various conditions, including twice freezing at -70 degrees C and thawing
      at 37 degrees C, slow thawing at 4 degrees C, refreezing the slowly thawed
      cryoprecipitate at -20 degrees C and thawing at 37 degrees C and maintaining the
      thawed cryoprecipitate at room temperature for 24 hours. The results indicated
      that factor VIII and von Willebrand factor antigen were effectively concentrated
      during the initial cryoprecipitation procedure. The cryoprecipitate which had
      been thawed and refrozen under the above conditions maintained factor VIII
      activities and concentrations of von Willebrand factor antigen similar to those
      in the original thawed cryoprecipitate. Furthermore, there was no significant
      loss of either of the coagulation factors in cryoprecipitate which was thawed in
      a warm water bath and stored for 24 hours at room temperature.

PMID- 8525106
TI  - Stability of canine factor VIII and von Willebrand factor antigen concentration
      in the frozen state.
AB  - The stability of factor VIII and von Willebrand factor antigen concentration in
      the frozen state was assessed. Citrated plasma was obtained from 10 healthy,
      mixed breed dogs and separated into 300 microliters aliquots. One aliquot was
      assayed immediately and the others were frozen at either -20 degrees C or -70
      degrees C. The activity of factor VIII and the concentration of von Willebrand
      factor antigen were measured after one week and one, two, three, four, five, six,
      eight and 10 months of storage. There were minor changes in both variables,
      particularly after four months, resulting in a decrease in the activity of factor
      VIII and an increase in the concentration of von Willebrand factor antigen. The
      changes were more pronounced at -20 degrees C. However, both factors remained
      relatively stable for the whole period.

PMID- 8525107
TI  - Increased concentrations of transferrin in the urine and serum of cattle with
      cardiomyopathy.
AB  - Bovine cardiomyopathy affects adult cattle of the Simmental/red Holstein and
      Holstein-Friesian breeds and is characterised clinically by signs of congestive
      heart failure. Animals with cardiomyopathy suffered a marked renal loss of
      transferrin (Tf). The urinary concentration of Tf discriminated very well between
      healthy and affected cattle, 93 per cent of the affected and 97 per cent of the
      healthy cows being identified correctly. In spite of the severe liver congestion
      and renal loss of Tf, cattle with cardiomyopathy had considerably higher
      concentrations of serum Tf than healthy cattle. This increase may help to
      compensate for the low serum concentration of iron in the affected animals. The
      pronounced changes in the concentrations of iron and transferrin in the serum had
      little effect on the haemogram of the diseased animals.

PMID- 8525108
TI  - Physical properties of particles of ipratropium and clenbuterol generated by
      equipment suitable for the inhalation of drugs by calves.
AB  - When solutions of ipratropium and clenbuterol were atomised at 300 kPa and 450
      kPa in equipment suitable for the inhalation of drugs by calves, the numbers,
      velocities and diameters of the particles produced were similar. When the
      pressure was increased to 600 kPa more of the particles were less than 2 microns
      in diameter and fewer were more than 7 microns in diameter, the fractions of the
      total mass of the solution generated in these size ranges were similarly
      increased and decreased, and the velocities of the particles were increased. At
      any given pressure, the numbers of particles of different sizes, and the
      proportions of the total mass generated, were similar for the solutions of
      ipratropium and clenbuterol, but a solution of saline produced more particles
      with a diameter less than 3 microns. Particles from the solution of ipratropium
      had the highest velocity and particles from the solution of clenbuterol had the
      lowest velocity.

PMID- 8525109
TI  - Oxygen cost of ventilation in the resting horse.
AB  - The purpose of this study was to develop a technique to measure the oxygen cost
      of ventilation and the values of ventilatory parameters in seven normal horses
      rebreathing carbon dioxide (CO2). All the horses responded to increased
      inspiratory levels of CO2 by increasing their tidal volume (VT) and frequency of
      breathing (Vf). The mean (SE) oxygen cost litre-1 of ventilation, measured at
      rates of ventilation greater than 200 litres min-1 was 1.7 (0.04) ml litre-1,
      similar to that of normal human subjects ventilating submaximally. It was
      concluded that the CO2 rebreathing test is a practical, non-invasive means of
      measuring the oxygen cost of breathing and the ventilatory response to CO2 in
      horses.

PMID- 8525110
TI  - Activation of the renin-angiotensin system in dogs with asymptomatic and
      symptomatic dilated cardiomyopathy.
AB  - Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were
      assessed in 23 dogs, nine of which had asymptomatic dilated cardiomyopathy (DCM)
      (New York Heart Association [NYHA] class I), eight had symptomatic DCM (NYHA
      class III) and six had severe congestive heart failure due to DCM (NYHA class
      IV). None of the dogs had received any drugs before the study. PRA was increased
      in dogs with DCM (NYHA classes III and IV) (median values 3.8 and 30.8 ng ml-1
      hour-1) compared with normal dogs (median 0.89 ng ml-1 hour-1). However, PRA was
      only marginally increased in dogs with DCM NYHA class I (P = 0.06). The PAC was
      also increased in dogs with DCM (NYHA classes III and IV) (median values 123 and
      600 pg ml-1) compared with normal dogs (median 61 pg ml-1). The PAC was not
      significantly increased in the early stage of DCM (NYHA class I). It was
      concluded that in dogs with DCM, the activity of the renin-angiotensin system
      (RAS) was increased in NYHA functional classes III and IV, and that the increase
      was correlated with the severity of the disease. The fact that the RAS tended to
      be activated in dogs with asymptomatic DCM supports the rationale of early
      therapeutic intervention with inhibitors of the angiotensin-converting enzyme
      (ACE) as first line therapy in congestive heart failure.

PMID- 8525111
TI  - Comparison of bromosulphthalein and indocyanine green clearance in sheep.
AB  - The kinetics of indocyanine green removal from the blood after a single
      intravenous injection were measured in sheep and compared with those of a single
      dose of bromosulphthalein given to the same animals 48 hours later. A single dose
      of 1.5 mg kg-1 of indocyanine green (ICG) was cleared in a double exponential
      manner. The hepatic uptake of ICG was not significantly different from that of
      bromosulphthalein (BSP) but its rate of excretion in bile was significantly lower
      (P < 0.05) and its rate of plasma reflux significantly higher (P < 0.05). The
      plasma distribution volumes of the two compounds were similar but the mean (SD)
      plasma clearance of ICG (435 [228.6] ml min-1) was significantly lower than that
      of BSP (626 [291.9] ml min-1) (P < 0.05). The retention of ICG 30 minutes after
      the injection was significantly higher than that of BSP (P < 0.01).

PMID- 8525112
TI  - An outbreak of diarrhoea associated with atypical rotaviruses in goat kids.
AB  - The presence of rotaviruses was investigated in the faeces of 31 goat kids in a
      dairy herd that experienced an outbreak of severe diarrhoea which caused
      dehydration, anorexia and prostration in seven (22.6 per cent) of them. All the
      affected animals were two to three days old. A group A-specific ELISA failed to
      detect rotaviruses in any of the samples but the characteristics electropherotype
      of group B rotaviruses was observed by electrophoresis in polyacrylamide gels in
      six of the animals. A highly significant statistical association between the
      shedding of rotavirus and the occurrence of diarrhoea was demonstrated. All the
      rotaviruses were detected in animals three to four days old. Cryptosporidium
      parvum, Clostridium perfringens and enterotoxigenic Escherichia coli were not
      detected in the seven diarrhoeic animals.

PMID- 8525113
TI  - Detection of bovine herpesvirus 1 in the semen of experimentally infected bulls
      by dot-blot hybridisation, polymerase chain reaction and virus isolation.
AB  - Two 18-month-old bovine herpesvirus 1 (BHV1)-seronegative bulls were inoculated
      experimentally with BHV1 via their prepuces. Semen collected at intervals was
      examined by optimised virus isolation, dot-blot hybridisation and the polymerase
      chain reaction (PCR) for detection of BHV1, and the infection was monitored
      serologically by using a virus neutralisation test. Antibodies were first
      detected 10 days after inoculation and were still present 40 days after
      inoculation. Semen collected from four to 40 days after inoculation was positive
      by PCR with Southern blot hybridisation whereas only the semen collected on day 4
      was positive by dot-blot hybridisation, virus isolation and PCR with ethidium
      bromide staining. These results indicate that the bulls started to shed the virus
      in semen before they developed any detectable antibody. PCR with Southern blot
      hybridisation was the most sensitive of the three methods and detected virus for
      the longest period.

PMID- 8525114
TI  - Pharmacokinetics of ampicillin administered intravenously and intraosseously to
      kittens.
AB  - An aqueous solution of ampicillin sodium (100 mg ml-1) was administered
      intravenously and intraosseously to six kitten at 50 mg kg-1 in a crossover
      study. Jugular vein blood samples were taken at intervals up to eight hours after
      treatment and the serum ampicillin concentration-time data, derived from a
      microbiological assay, were analysed pharmacokinetically. The disposition
      kinetics of ampicillin administered by the two routes were very similar. The mean
      elimination half-life (t1/2 beta), the area-derived volume of distribution
      (Varea) and the total body clearance (ClB) values after the intravenous and
      intraosseous treatment were 86.3 and 79.0 minutes, 0.9 and 0.8 litre kg-1 and 7.3
      and 7.6 ml min-1 kg-1, respectively. No side-effects related to the intraosseous
      administration of the drug were observed.

PMID- 8525115
TI  - Prophylactic efficacy of phenytoin, acetazolamide and hydrochlorothiazide in
      horses with hyperkalaemic periodic paralysis.
AB  - Horses with hyperkalaemic periodic paralysis were challenged with an oral dose of
      potassium chloride, and the prophylactic efficacy of phenytoin, acetazolamide and
      hydrochlorothiazide was evaluated, with at least three weeks separating the
      trials of each drug. After the administration of potassium chloride without
      prophylactic medication the horses' clinical signs ranged from generalised fine
      muscle fasciculations to gross tremors, and weakness with occassional prolapse of
      the nictitating membrane; plasma potassium concentration increased significantly
      (P < 0.01) from 4.0 +/- 0.2 to 6.0 +/- 1.01 mmol litre-1. After treatment with
      acetazolamide the administration of potassium chloride resulted in a significant
      (P < 0.02) increase in plasma potassium from 3.7 +/- 0.3 to 4.5 +/- 0.4 mmol
      litre-1 and two of five horses showed clinical signs unless the dosage was
      increased from 2.2 to 4.4 mg kg-1 twice daily. Three of the four horses treated
      with hydrochlorothiazide showed clinical signs but their plasma potassium did not
      rise significantly (3.6 +/- 0.3 to 4.6 +/- 1.0 mmol litre-1). None of the five
      horses treated with phenytoin showed clinical signs despite a significant
      increase in plasma potassium from 3.8 +/- 0.6 to 5.3 +/- 1.1 mmol litre-1 (P <
      0.05). In general the clinical signs were not correlated consistently with the
      plasma levels of potassium, and phenytoin appeared to prevent the clinical signs
      in spite of the hyperkalaemia.

PMID- 8525116
TI  - Hypoxia-inducible gene expression.
AB  - When oxygen is lacking the cellular production of some hormones, cytokines and
      glycolytic enzymes can be dramatically increased by a hypoxia-induced increase in
      the expression of the respective genes that encode for these proteins. The most
      progress in understanding how the transcription of genes is increased under
      hypoxic conditions has been made by studying the hypoxia-inducible expression of
      the erythropoietin gene. Elucidating the oxygen sensitive enhancer elements of
      the erythropoietin gene has prompted studies on other oxygen-regulated genes. The
      transcription-regulating proteins that are induced with hypoxia bind to closely
      related regulatory DNA sequences that control the expression of the genes for
      erythropoietin, the vascular endothelial growth factor and a number of glycolytic
      enzymes. It became evident that the hypoxia-inducible enhancer may be part of a
      widespread oxygen-sensing mechanism acting in a wide variety of mammalian cells.
      Comparison with the oxygen sensor system in the bacterium Rhizobium meliloti
      revealed some similarities with the putative oxygen sensor in mammalian cells.
      This sensor is thought to respond to hypoxia by inducing the signalling cascade
      that results in binding of the transcription factors to their respective enhancer
      elements to induce transcription of the respective gene.

PMID- 8525117
TI  - Intracarotid substance P infusion inhibits ventilation in the goat.
AB  - Substance P (SP) has been proposed as an excitatory neuromodulator of the carotid
      body (CB) response to hypoxia based on data from the cat and rat. The role of SP
      as a CB neuromodulator in the goat is unknown. Awake (n = 14) and chloralose
      anesthetized goats (n = 6) were used to investigate the effects of intracarotid
      (IC) SP infusions (1-6 micrograms.kg-1.min-1) and bolus injections (6 micrograms
      kg-1) to the CB intact and denervated (CBX) sides (control) on mean ventilation
      (VE) and mean blood pressure (MBP). In awake goats VE was decreased by infusion
      or bolus SP injection at a dose of 6 micrograms.kg-1 (P < 0.05) and occurred with
      infusions to the intact or CBX sides. MBP was elevated with SP infusion to either
      the CB intact or CBX sides at all SP doses. The SP antagonist CP-96,345 (0.1
      mg.kg-1, IV) blocked the decrease in VE induced by SP in normoxia and
      significantly increased the hypoxic ventilatory response (PaO2 = 40 torr). In
      anesthetized goats, IC injections of SP (1 to 6 micrograms.kg-1) reduced phrenic
      activity and MBP before and after CBX. In only one of five goats airway pressure
      was increased suggesting that bronchoconstriction was not a cause for the reduced
      ventilatory and phrenic activity induced by SP. Immunohistochemistry provided
      evidence of SP in CB nerve fibers and terminals, carotid sinus nerve axons and
      petrosal ganglion cells, but not in type I glomus cells. Our results do not
      support the view that SP is an excitatory neuromodulator of CB chemotransduction
      in the goat.

PMID- 8525118
TI  - Effects of superior laryngeal nerve section on ventilation in neonatal guinea
      pigs.
AB  - Ventilation was measured by barometric plethysmography in conscious, 10-14 day
      old guinea-pigs with superior laryngeal nerves (SLN) intact or sectioned. In SLN
      intact animals, hypercapnia caused concentration-dependent increases in
      respiratory frequency, tidal volume and minute ventilation but hypoxia had no
      effects. SLN section reduced respiratory frequency and minute ventilation during
      normoxia and reduced the ventilatory response to 6% CO2. In the same animals
      under anaesthesia, upper airway (UA) cooling decreased respiratory frequency and
      increased peak inspiratory flow in SLN-intact but not in SLN-sectioned animals.
      CO2 in the UA caused a tachypnoea which was also present in SLN-sectioned animals
      and when the nose was bypassed. These results show that UA afferents participate
      in ventilatory control in neonatal guinea-pigs. Moderate UA cooling causes a SLN
      dependent decrease in respiratory frequency but UA CO2 causes tachypnoea which is
      not SLN-mediated and contrasts with the inhibitory effect of UA CO2 on breathing
      described in adults of other species.

PMID- 8525119
TI  - Effect of changes in airway surface liquid on laryngeal receptors and muscles.
AB  - The effects of aerosolizing distilled water and isosmolal dextrose in the
      isolated larynx on the activity of pressure-responsive receptors and laryngeal
      muscles were studied in anesthetized dogs. Following water aerosolization, the
      mean discharge of pressure-responsive laryngeal mechanoreceptors during upper
      airway breathing and occlusion was 151% and 138% respectively of that present
      after saline aerosolization. During delivery of water aerosol, the peak activity
      of the posterior cricoarytenoid muscle increased to 229 +/- 56% of control; no
      effects were present on the thyroarytenoid muscle activity. Saline or isosmolal
      dextrose aerosols did not have any effect on the activity of either muscle. The
      reflex increase in posterior cricoarytenoid muscle activity due to laryngeal
      negative pressure was enhanced (163%) when the negative pressure challenge was
      repeated following distilled water aerosol. These results suggest that alteration
      in laryngeal surface liquid composition modifies the response of pressure
      responsive laryngeal receptors and thereby the reflex activation of airway
      patency maintaining muscles.

PMID- 8525120
TI  - Relief of distress of breathholding: separate effects of expiration and
      inspiration.
AB  - It is well known that rebreathing relieves the respiratory distress of maximal
      breathholding despite worsening blood gases, and it has been suggested that vagal
      input has a role in ameliorating this sensation via activation of pulmonary
      stretch receptors (PSR). However, it is believed by divers that expiration can
      lead to partial relief of distress of breathholding at total lung capacity (TLC)
      allowing a prolongation of breathholding. We studied the independent effects of
      an expiration and an inspiration on relief of respiratory distress of
      breathholding. Subjects held their breath at TLC until distress became
      intolerable, then exhaled to FRC and performed a second breathhold. When distress
      again became intolerable, subjects inspired to TLC a gas that resembled their
      exhaled gas and performed a third breathhold. Subjects noted partial relief with
      both an expiration and an inspiration. However, relief of distress was greater
      and the subsequent breathhold longer after an inspiration than after an
      expiration. We suggest that relief of distress after an inspiration is compatible
      with the inhibitory effect of PSR input; the mechanism of relief that occurs
      after an expiration is as yet uncertain.

PMID- 8525121
TI  - Decreased carotid body hypoxic sensitivity in chronic hypoxia: role of dopamine.
AB  - Previously we showed that prolonged exposure to severe hypoxia produces decreased
      peripheral chemoreceptor responsiveness to hypoxia and attenuates central nervous
      system (CNS) chemosensory translation, which together may contribute to the
      decreased hypoxic ventilatory response (HVR) in chronic hypoxia. In this study,
      we sought to determine whether the central or peripheral activity of endogenous
      dopamine modulates this decreased HVR. We examined the effects of peripheral and
      central dopamine receptor blockade on HVR and carotid sinus nerve (CNS) response
      to hypoxia in controls and in cats exposed to a simulated altitude of 5500 m for
      3 weeks. Domperidone increased CSN response to hypoxia in hypoxic cats to levels
      similar to those observed in controls. HVR was also augmented by domperidone in
      hypoxic cats, but remained below that of controls. As a result, the CNS
      chemosensory translation remained reduced in hypoxic animals. We further treated
      animals with haloperidol. However, this combined treatment with domperidone and
      haloperidol led to no further increase in CSN or ventilatory responses to
      hypoxia, or in CNS chemosensory translation in hypoxic cats. Thus, decreased HVR
      in hypoxic cats is mediated both by depression of hypoxic sensitivity of the
      carotid body, which is largely dopaminergic, and by decreased CNS chemosensory
      translation which must involve non-dopaminergic mechanisms.

PMID- 8525122
TI  - Central effects of 5-HT on respiratory and hypoglossal activities in the adult
      cat.
AB  - The activities of the diaphragmatic, internal intercostal and hypoglossal
      innervated muscles were studied in adult decerebrate cats in response to 5-HT and
      related agents (8-OH-DPAT and DOI). The drugs were placed on the floor of the
      IVth ventricle. The mean respiratory frequency (Fi) increased (124-193% of the
      control value) within 3 min of the 5-HT application, and decreased thereafter (30
      90%). The mean Ti and Te changed similarly, but opposite to Fi. With some delay,
      the hypoglossal-innervated muscles were tonically activated or exhibited
      increased activities. Methysergide pretreatment completely blocked the effect of
      5-HT on all the respiratory parameters and the hypoglossal-innervated muscles
      activities. The responses to 8-OH-DPAT and DOI indicate that 5-HT modulates the
      respiratory frequency via activation of both 5-HT1A and 5-HT2 receptors.
      Nevertheless, the effect of 5-HT on both the expiratory and hypoglossal
      innervated muscles seems to depend on 5-HT2 receptors activation only.

PMID- 8525123
TI  - Hypoxic response is inversely related to degree of exercise hyperventilation.
AB  - The Dejours hyperoxic test has been used to quantitate peripheral chemoreceptor
      contribution to the hyperpnea of exercise. The strength of this drive, measured
      by the percent reduction in ventilation, varies among individuals and is lacking
      in chemodenervated humans, who also fail to manifest a hyperventilatory response
      in heavy exercise. We reasoned that greater hyperventilation in exercise above
      the anaerobic threshold ought to be associated with greater hypoxic (carotid
      body) drive. The present study tested this hypothesis. In 17 naive subjects,
      carotid body O2 chemosensitivity was tested repeatedly during exercise above the
      ventilatory anaerobic threshold (VAT) using 2 breaths of O2. The response to
      these transients was quantitated by the percentage change in ventilation, and
      exercise hyperventilation was quantitated by VE in excess of VCO2 predicted from
      the slope of delta VE/delta VCO2 below VAT in incremental exercise. Contrary to
      expectations, there was an inverse relation between the degree of exercise
      hyperventilation and the percentage reduction in exercise ventilation in response
      to O2. The significance of this observation and its integration with current
      thinking of the role of the peripheral chemoreceptor in mediating
      hyperventilation of heavy exercise is discussed.

PMID- 8525124
TI  - Submental stimulation and supraglottic resistance during mouth breathing.
AB  - We studied submental stimulation on supraglottic resistance (Rsg) in 5 normals
      and 6 patients with obstructive sleep apnea. We then examined the most effective
      sites of stimulation in the submental regions, and the relationships between Rsg
      and stimulation frequency and voltage in the supine position. Inspiratory and
      expiratory Rsg's were obtained as the slope of the linear portion of the pressure
      flow relation determined at zero flow. Before stimulation, inspiratory and
      expiratory Rsg's were 0.76 +/- 0.06 (means +/- SE) and 0.61 +/- 0.02 cmH2O.L
      1.sec, respectively, in normals, and 1.04 +/- 0.20 and 0.92 +/- 0.29 cmH2O.L
      1.sec, respectively, in patients. Stimulation in the proximal half submental
      region with surface electrodes 1 cm apart decreased inspiratory and expiratory
      Rsg's in patients, and inspiratory Rsg in normals. Inspiratory Rsg measured in
      this submental region showed a stimulation frequency-and voltage-dependency in
      both groups, but expiratory Rsg did not. These findings suggest that submental
      stimulation in the proximal half region widens the supraglottic airway during
      mouth breathing and probably involves the upper airway muscles.

PMID- 8525125
TI  - Coupling of ventilation and gas exchange during transitions in work rate by
      humans.
AB  - The dynamic responses of expired ventilation (VE) following transitions in work
      rate were studied during step increases and decreases, and during pseudorandom
      binary sequence (PRBS) changes in work rate. Six healthy men completed multiple
      repetitions of each test type under conditions of hypoxia (fractional inspired
      O2, FIO2 = 0.14), room air and hyperoxia (FIO2 = 0.70). Neither potentiation nor
      attenuation of the carotid chemoreceptors, with hypoxia or hyperoxia
      respectively, influenced the magnitude or duration of the phase 1 response at the
      onset of exercise. However, the off-transient phase 1 was smaller with hypoxia
      than normoxia or hyperoxia. The time course of phase 2 was faster in hypoxia and
      slower in hyperoxia, but there was symmetry between on- and off-responses. This
      was counter to predictions of asymmetry based on the short-term potentiation
      hypothesis. Tight coupling existed for breath-by-breath VE relative to CO2 output
      during PRBS exercise, especially in hypoxia (r2 = 0.40 +/- 0.08; 0.64 +/- 0.03;
      and 0.71 +/- 0.05 for hyperoxia; normoxia; and, hypoxia), but poorer coupling
      existed to O2 uptake, especially in hyperoxia (r2 = 0.09 +/- 0.04; 0.37 +/- 0.05;
      and 0.46 +/- 0.07). These data are consistent with neural factors in phase 1, and
      humoral mediation of phase 2 responses during dynamic exercise in healthy
      subjects.

PMID- 8525126
TI  - Properties of lavage material from excised lungs ventilated at different
      temperatures.
AB  - We studied the phospholipid (PL) and protein contents, the PL composition, and
      some of the surface properties of lavage materials obtained from freshly excised
      rat lungs and excised lungs which had been ventilated at different temperatures
      (22, 37, and 42 degrees C). Ventilation (60 breaths/min) was carried out at
      constant tidal volume with periodic sighs for one hour. Although there is
      slightly more lavageable PL and protein in lungs ventilated at 22 degrees C than
      in freshly excised lungs, there is no difference in the PL composition or surface
      properties of lavage materials from these lungs. However, as the temperature at
      which lungs are ventilated is increased to 37 degrees and 42 degrees C, there
      is(are): 1) a reduction in lavage fluid PL, 2) a reduction in the relative
      amounts of total phosphatidylcholines (PC) and disaturated PC (DSPC), the major
      surface active component of pulmonary surfactant, 3) an increase in unsaturated
      PC, and 4) increases in total protein and nonsedimentable protein (100,000 g; 2
      hr) in the lavage materials. There are also differences in the surface properties
      of the lavage materials from lungs ventilated at higher temperatures when
      compared with freshly excised lungs or lungs ventilated at 22 degrees C, probably
      as a result of the changes in composition. Maximal surface tension is greater for
      lavage materials from lungs ventilated at 37 degrees C. For lungs ventilated at
      42 degrees C, maximal and minimal surface tension values are increased. These
      results demonstrate that there are differences in the composition and surface
      properties of alveolar lavage materials from excised lungs ventilated at
      different temperatures.

PMID- 8525127
TI  - Lower circulating insulin-like growth factor I and 1,25-dihydroxyvitamin D levels
      in preeclampsia.
AB  - OBJECTIVE: To assess whether the circulating levels of insulin-like growth factor
      I (IGF-I) are lower in preeclamptic than in normotensive pregnant women and
      whether serum concentrations of IGF-I are associated with those of 1,25
      dihydroxyvitamin D (1,25-(OH)2D). STUDY DESIGN: The study was cross-sectional and
      was done at 26.7 to 39.7 weeks of pregnancy. The results obtained from
      preeclamptic women were compared with those obtained from normotensive pregnant
      women with the same gestational age (control group). SETTING: All the volunteers
      were patients attending the General Hospital of Mexico City and all laboratory
      measurements were done at the National Institute of Nutrition Salvador Zubiran,
      Mexico City. SUBJECTS: The study included 26 preeclamptic women and 26
      normotensive pregnant women. All participated voluntarily and signed an informed
      consent. PROCEDURE: The following measurements were done: serum concentrations of
      IGF-I, 1,25-(OH)2D, intact parathyroid hormone (PTH), inorganic phosphorus,
      creatinine, and total and ionic calcium and magnesium. Also urinary calcium and
      creatinine clearance were measured and dietary and anthropometric data were
      obtained. All determinations were done blindly. Comparisons between groups were
      done using the Mann-Whitney U-test. Associations between variables were tested
      using the Spearman rank correlation and stepwise regression. RESULTS: Serum IGF-I
      levels were 26.1 +/- 10.2 nmol/L (mean +/- SD) in the preeclamptic group and 40.9
      +/- 14.3 in the normotensive group (p = 0.0003); serum 1,25-(OH)2D levels were
      43.6 +/- 8.2 pg/mL in the preeclamptic group and 52.1 +/- 10.2 in the
      normotensive group (p = 0.005). Serum intact PTH was similar in both groups.
      Serum levels of IGF-I, 1,25-(OH)2D, and intact PTH correlated significantly in
      the control group. In the preeclamptic group correlation was found only between
      IGF-I and 1,25-(OH)2D. CONCLUSIONS: Our study brings out two interesting
      observations. First, that serum IGF-I levels were significantly lower in
      preeclamptic than in control pregnant women; and second, the existence of a
      significant correlation between serum IGF-I and 1,25-(OH)2D concentrations in
      both preeclamptic and normotensive pregnant women.

PMID- 8525128
TI  - High levels of TH2 cytokine gene expression in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with a clear
      imbalance in the network made up of different cytokines. However this statement
      has been derived from studies which have focused on the analysis of some specific
      cytokines and few have simultaneously analyzed those cytokines that could be
      involved in the pathogenesis of SLE. Therefore, we decided to analyze interleukin
      IL-1b, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-a (TNF-a) and gamma
      interferon (IFN-g) gene expression in peripheral blood mononuclear cells from 17
      women with SLE and 10 normal females by a coupled reverse transcriptase
      polymerase chain reaction technique. High gene expression of IL-4, IL-6, IL-10
      and TNF-a was found in SLE patients as compared to normal subjects. The
      expression of IL-1b, IL-2 and IFN-g genes was low or undetectable. The resulting
      high level of cytokines with strong effect on proliferation and differentiation
      of B lymphocytes in SLE could be responsible for the characteristic B cell
      hyperactivity and autoantibody production seen in SLE.

PMID- 8525129
TI  - [Resistance of Mycobacterium tuberculosis in Mexican patients. I. Clinical
      features and risk factors].
AB  - OBJECTIVE: To determine the clinical manifestations associated with resistant M.
      tuberculosis infection and the antimicrobial resistance in isolates from Mexican
      patients. STUDY DESIGN: Epidemiological surveillance. PATIENTS: Tuberculosis
      confirmed cases. METHODS: Primary resistance: no history of treatment prior to
      diagnosis. The following critical concentrations (micrograms/mL) were used for
      susceptibility: isoniazid 0.2 and 1; rifampin 1 and 5; ethambutol 5 and 10;
      streptomycin 2 and 10; ethionamide 5; kanamycin 6; and para-aminosalicylic acid
      (PAS) 2 and 10. RESULTS: Eighty-four patients with a mean age of 44.7 years were
      included; 54 men (64%) and 30 women (36%); most patients were from the Mexico
      City metropolitan area. In 34 patients there was clinical information available,
      26 presented fever and weight loss and 8 respiratory symptoms. Fifty-nine
      patients (70%) were infected by pan-susceptible M. tuberculosis, and 25 (30%) by
      a resistant isolate; 17 (68%) of them were resistant to at least two drugs, 16
      (64%) to isoniazid and rifampin. The proportion of resistance was: isoniazid 24%,
      rifampin 19%, streptomycin 12%, ethambutol 10%, PAS 9%, etionamide 7%, and
      kanamycin 6%. Of 47 patients without previous treatment, eight had a resistant
      microorganism (17%): 9% resistant to isoniazid, 6% to rifampin, 2% to
      streptomycin, 6% to PAS and 6% multiresistant. Of 37 patients with history of
      previous treatment for tuberculosis, 17 (46%) had a resistant isolate; 44% were
      resistant to isoniazid, 35% to rifampin, 24% to streptomycin, 19% to ethambutol,
      12% to PAS and 35% multiresistant. Of the 84 patients, four were physicians
      infected by a resistant isolate, and seven HIV-infected patients, one with a
      multiresistant isolate, and another with isoniazid resistance. CONCLUSIONS:
      Antimicrobial resistance among M. tuberculosis is alarmingly high in Mexico City;
      these results emphasize the importance of case detection and early isolation of
      patients.

PMID- 8525130
TI  - [Physico-chemical properties related to gastrointestinal function of 6 sources of
      dietary fiber].
AB  - The physicochemical properties of the six sources of dietary fiber more commonly
      consumed in Mexico were studied. The knowledge of these properties may allow a
      prediction of the functional effect of the fibers on the GI tract. The content of
      dietary fiber varied from 43% in wheat bran (WB) to 87% in Psyllium plantago
      (PP). Glucomannan (GM) showed the highest proportion of soluble fiber (97%)
      followed by dried cactus from Opuntia sp (DC) (28%) and PP (13%), whereas WB and
      soy isolate (SI) showed the highest proportion of insoluble fiber (95 and 92%,
      respectively). PP and GM showed a higher water holding capacity and viscosity and
      a lower ion exchange capacity: we anticipate that these fibers would be more
      effective to regulate plasma levels of glucose and cholesterol in contrast, WB
      and SI with a lower water holding capacity and viscosity and a higher proportion
      of insoluble fiber would be more effective to increase fecal bulk. Fibers from DC
      and from cactus fiber isolate were intermediate in these responses.

PMID- 8525131
TI  - [7 cases of carcinoma of the distal choledochus].
AB  - Seven patients with carcinoma of the lower third of the extrahepatic bile duct
      over a twenty year period, were analyzed with emphasis to the presentation,
      laboratory, surgical findings, histology and outcome. There were four males and
      three females. The mean age was 59 years (range 53 to 68). All patients presented
      jaundice, abdominal pain and weight loss. Serum bilirubin levels were over 5
      mg/dL in six patients (86%). The most useful diagnostic studies were endoscopic
      cholangiography, percutaneous cholangiography and computed tomography. All
      patients underwent a Whipple procedure. There was no operative mortality. In the
      long term follow-up, three patients were free of disease, and four had died.
      Tumor recurrence was high (43%) in spite of the curative resection.

PMID- 8525132
TI  - [Ablation of the atrioventricular node using radiofrequency in a cirrhosis
      patient].
AB  - The ablation of cardiac arrhythmias by radiofrequency has changed radically the
      treatment of arrhythmias. We present the case of a woman with cirrhosis and no
      structural heart disease, who was severely limited in her activities because of
      drug-refractory paroxysmal supraventricular tachyarrhythmias. She underwent an
      atrio-ventricular node ablation by radiofrequency. She was discharged with no
      antiarrhythmic drugs and on a permanent cardiac pacing. She showed obvious
      improvement in her quality of life.

PMID- 8525133
TI  - [2 cases of neutropenic enteropathy and bone marrow hypoplasia. An association
      not reported in Mexico].
AB  - Neutropenic enterocolitis (NE) is a serious complication in neutropenic patients;
      it often affects the cecum and the ascending colon. Most cases have been reported
      in neutropenic patients after chemotherapy for hematologic neoplasms, and some in
      association with conditions such as rheumatoid arthritis, benign cyclic
      neutropenia, and solid neoplasms. As far as we know, four cases of NE associated
      to AA (aplastic anemia, hypoplastic bone marrow) have been previously reported,
      two of them with autopsy studies. The macroscopic findings in the enterocolonic
      lesions were not illustrated. We report the first two cases in Mexico. The NE was
      neither clinically nor radiographically suspected initially, i.e. the morphologic
      diagnosis of their colonic lesions were amebic colitis in one and edematous
      ulcerated colitis in the other. Medical treatment without surgery was instituted.
      Both died. The macroscopic aspect of the enterocolonic lesions in NE associated
      to aplastic anemia in our two patients was similar to that in NE associated to
      hematologic neoplasms. In Mexico there is little experience in the clinical,
      radiographic or morphologic diagnosis of this rare association.

PMID- 8525134
TI  - [Probable coumarin poisoning upon ingestion of an anti-inflammatory agent].
AB  - Warfarin overdose leads to hypoprothrombinemia and bleeding diathesis. We report
      here the case of a 47 year old woman who ingested an overdose of a non-steroidal
      anti-inflammatory drug, sold in Mexico under the name of Wobenzym (R), and
      containing, according to the manufacturer: pancreatin, bromelin, papain, lipase,
      amylase, trypsin, alpha chymotrypsin and rutin. She developed skin, urinary and
      gastrointestinal bleeding and was found to be apparently under the effect of a
      coumadin overdose, i.e. prolonged prothrombin time, prolonged activated
      thromboplastin time, and low functional and antigenic levels of prothrombin. A
      platelet count, and the thrombin, reptilase and bleeding times were normal. All
      laboratory and clinical abnormalities reverted to normal by using fresh frozen
      plasma and parenteral vitamin K. In addition, we were able to show that the
      commercial preparation could prolong the prothrombin time in rabbits and, by high
      performance liquid chromatography, a pike consonant with purified coumadin was
      found in the drug. It is concluded that this drug is probably contaminated by
      coumadin, and that physicians must be aware of its potential side effects.

PMID- 8525135
TI  - [Conceptualization and measurement of the quality of life of cancer patients].
AB  - We have reviewed three attributes related with quality of life of cancer
      patients: definition, objectives and methods of measurement. The definition most
      widely accepted is that quality of life is the "subjective evaluation of life as
      good or satisfactory as a whole". It is proposed that quality of life should be
      included as an outcome variable in clinical trials, especially in palliative
      care; in addition it could be useful in clinical decisions and in planning care
      for cancer patients. Finally we have reviewed critically several scales that are
      being used for the measurement of quality of life of cancer patients.

PMID- 8525136
TI  - [Progesterone and its metabolites in central nervous system function].
AB  - Progesterone (P4) and its metabolites are involved in several functions of the
      central nervous system (CNS). These steroids participate in neuronal
      excitability, reproduction and sexual behavior. P4 and its metabolites exert
      their effects on neurons and glial cells through several mechanisms that include
      the interaction of the steroids with: 1) intracellular specific receptors; 2)
      modulatory sites located in neurotransmitter receptors; and 3) ionic channels. By
      these mechanisms, modifications in gene expression, second messengers' production
      and ion conductance are induced. The activities of the P4 metabolites have been
      mainly related to membrane effects, whereas for P4, the transcriptional and
      translational effects are mediated by intracellular receptors. Thus, these
      steroids can modify the CNS functions at short (milliseconds), medium (minutes)
      or long term (hours or days) lapses. The knowledge of the molecular mechanisms
      involved in the actions of P4 and its metabolites in the CNS will contribute to
      the understanding of fundamental biological processes such as sexual behavior and
      reproduction, and it will open the possibility of alternative therapies in the
      treatment of some neurologic and psychiatric disorders such as epilepsy, anxiety,
      premenstrual syndrome, and cerebral tumors which possess hormonal regulation.

PMID- 8525137
TI  - [Aspiration biopsy].

PMID- 8525138
TI  - Renal reserve: early work and personal reminiscences from the 1940s.
AB  - The circumstances under which the author entered the field dealing with the
      effects of dietary protein intake on renal functions are discussed. The general
      state of knowledge in this field is outlined as it was in the late 1940s.
      Personal reminiscences of day-to-day operations of the laboratory, interactions
      with colleagues, and other thoughts and experiences of the author are described.

PMID- 8525139
TI  - Renal reserve: a functional view of glomerular filtration rate.
AB  - The hyperfiltration theory challenged the view that glomerular filtration rate is
      a fixed function as well as that there is a good correlation between GFR and
      renal parenchymal damage. Glomerular filtration rate is a dynamic parameter that
      is diet-dependent and can be altered by hemodynamic maneuvers. Therefore, it is
      not a good indicator of renal lesion. The renal reserve is an indicator of the
      workload per nephron and may be a useful parameter to assess the progression of
      renal disease in the presence of dietary or pharmacological intervention.

PMID- 8525140
TI  - Intrarenal mechanisms of renal reserve.
AB  - Acute ingestion of protein and intravenous infusion of amino acids are known to
      stimulate increases in renal blood flow and glomerular filtration rate (GFR) in
      animals and humans. Although some investigators believe that these changes are
      mediated by a circulating hormonal factor, there is considerable evidence that
      intrinsic intrarenal mechanisms such as tubular transport of amino acids and
      sodium, and the tubuloglomerular feedback mechanism, are involved in this renal
      hemodynamic response, and that extrarenal factors may not be required.

PMID- 8525141
TI  - Role of angiotensin in the regulation of renal response to proteins.
AB  - Intrarenal and extrarenal humoral factors have been proposed as mediators and
      modulators of the renal hyperemic response to amino acid infusion. Among the
      potential modulators, angiotensin II (AII) constitutes the most important
      candidate due to its critical role in the control of glomerular and tubular
      function. The modulatory effect of AII has been assessed by (1) measuring the
      changes in plasma renin activity (PRA)/AII during the normal hyperemic response,
      and (2) by assessing the levels of PRA/AII and the response to AII-suppressing
      agents in conditions with no vasodilatory response during amino acid infusion.
      Administration of a protein load in normal animals or humans does not modify
      PRA/AII. Absence of a vasodilatory response in various experimental conditions
      (nitric oxide blockade in normal rats, experimental models of hypertension,
      diabetes mellitus, chronic glomerulonephritis, cyclosporine administration) is
      characterized by a significant decrease in proximal tubular reabsorption during
      amino acid infusion. Converting enzyme inhibitors or AII receptor antagonist
      restore normal tubular function and the increase in glomerular filtration rate
      during amino acid infusion. Absence of a vasodilatory response is also associated
      with increases in kidney AII levels in some of these conditions. These results
      suggest that (1) AII modulates the amino acid-induced hyperemia through its
      inhibitory effect on proximal tubular reabsorption and activation of the
      tubuloglomerular feedback system, and (2) that the expression of the modulatory
      effect of AII may depend on the interaction between AII and other intrarenal
      systems like nitric oxide.

PMID- 8525142
TI  - Nitric oxide and the renal hemodynamic response to proteins.
AB  - This article examines the potential role of nitric oxide in the renal
      hyperfiltration and vasodilation associated with acute amino acid infusions and
      changes in habitual protein intake. The impact of acute and chronic blockade of
      nitric oxide synthesis on basal renal hemodynamics and on the renal response to
      protein are examined. Data linking nitric oxide to other well-characterized
      modulators of the response to protein are reviewed. New insights into the role of
      nitric oxide and L-arginine in the pathogenesis of progressive renal injury are
      examined. The data strongly suggest a role for nitric oxide in the complex
      physiological reply to protein feeding. Modulation of dietary L-Arg might be an
      important therapeutic maneuver in the prevention of acute and chronic renal
      injury.

PMID- 8525143
TI  - Renal hemodynamic response to intravenous and oral amino acids in animals.
AB  - Oral or parenteral application of amino acids leads to marked hyperfiltration and
      increased of renal plasma flow. Amino acids stimulate the release of glucagon,
      which increases hepatic production and release of cyclic adenosine monophosphate
      (cAMP). In the kidney, the combined effect of cAMP and glucagon increases
      glomerular filtration rate (GFR), possibly by reducing NaCl concentration at the
      macula densa and depression of the tubuloglomerular feedback. Vasopressin
      dependent urea recycling and delivery to the thick ascending limb could similarly
      reduce NaCl concentration at the macula densa. Beyond that, amino acids may
      trigger a hepatorenal reflex or directly interfere with renal function.
      Mechanisms invoked include dopamine from renal nerves, prostaglandins, nitric
      oxide (NO), and angiotensin II. At this point, it is not clear to which extent
      the described mechanisms participate in, permit, or fully account for the
      hyperfiltrative effect of amino acids.

PMID- 8525144
TI  - Tubule effects of glomerular hyperfiltration: an integrated view.
AB  - An increase in glomerular filtration rate (GFR) induces adaptive changes in
      tubular function to prevent the urinary loss of water and electrolytes. This is
      also true for acid-base balance: the increase in filtered bicarbonate load will
      stimulate H+ secretion at the level of several segments including the proximal
      tubule, the loop of Henle, and the distal tubule. There is an activation of both
      the luminal Na+/H+ exchanger and H(+)-ATPase, and basal-lateral Na(+)-HCO3-
      cotransport which allows an increase in luminal H+ secretion and basal lateral
      HCO3- exit. The stimulation of electrolyte reabsorption is very important at the
      level of the thick ascending limb of Henle, a segment that shows consistent
      hypertrophy in many models of hyperfiltration. Along this segment, increased Na+
      and Cl- reabsorption has been found in rats receiving a high-protein diet. The
      ensuing reduced Na+ and Cl- concentrations, at the level of the macula densa,
      could weaken the signal responsible for initiating the tubuloglomerular feedback
      (TGF), thus allowing GFR to increase.

PMID- 8525145
TI  - Renal effects of intravenous amino acid administration in humans with and without
      renal disease: hormonal correlates.
AB  - In the early 1980s, renewed interest was focused on the possible protective
      effect of protein-restricted diets on the progression of human renal
      insufficiency. This resulted from observations in several models of experimental
      renal failure in which protein-restricted diets attenuated the progression of
      renal insufficiency. Micropuncture studies in subtotally nephrectomized rats and
      rats with other causes of renal insufficiency had shown that glomerular
      hyperfiltration occurred in remnant glomeruli to compensate for the loss of renal
      function. However, such rats developed progressive glomerular sclerosis. In rats
      fed a protein-restricted diet, such glomerular hyperfiltration did not occur and
      the development of renal insufficiency was postponed. Thus, it was hypothesized
      that the compensatory hyperfiltration of remnant glomeruli was ultimately harmful
      to the kidneys. At the same time, concomitant research was started to establish
      methods to show the presence of glomerular hyperfiltration in humans, in an
      attempt to trace patients who could benefit from protein-restricted diets. Thus,
      the effects of an acute protein load, given as a meat meal or intravenous
      administration of amino acids, on renal hemodynamics were investigated resulting
      in the introduction of the concept of renal reserve capacity. In the present
      report, the effects of intravenously administered amino acids on renal
      hemodynamics of subjects with and without renal disease will be discussed.
      Special interest will be focused on the amino acid-induced hormonal changes and
      their involvement in the renal hemodynamic changes observed during amino acid
      infusion.

PMID- 8525146
TI  - Renal response to an acute oral protein load in healthy humans and in patients
      with renal disease or liver cirrhosis.
AB  - This article analyzes 57 reports published in the years 1983 through 1964 that
      addressed the issue of the renal hemodynamic response to an oral protein load.
      Seventy-three groups are reported in those studies: 52 were healthy subjects (n =
      627) and 21 had renal disease (n = 256); 47 were studied using inulin (n = 407
      healthy people and 112 renal patients); 26 groups were studied using creatinine
      (n = 220 healthy people and 144 renal patients). Patients with liver cirrhosis
      were also analyzed. There was great heterogeneity in methodology used,
      emphasizing the need for standardization. The role of plasma amino acids,
      glucagon, insulin, growth hormone, PGE2, 6-ketoPGA1 alpha, brain-gut peptides,
      ANP, AVP, dopamine, and kinins in promoting the renal hemodynamic response to an
      oral protein load is discussed.

PMID- 8525147
TI  - Renal reserve in pregnancy.
AB  - Normal pregnancy is associated with increases in renal blood flow and glomerular
      filtration rate, increases that are probably the most dramatic seen under any
      physiological conditions. Yet, despite these marked elevations in baseline
      values, most investigators have found that the kidneys of pregnant animals and
      humans are capable of further vasodilation and hyperfiltration in response to an
      acute protein load or amino acid infusion, ie, renal reserve is maintained in
      pregnancy.

PMID- 8525148
TI  - Renal functional reserve in children.
AB  - Renal reserve in children is related to changes in renal plasma flow (RPF) in
      health and renal disease. Peak glomerular flow rate (GFR) correlates with peak
      RPF. The renal hemodynamic response to protein is associated with a decrease in
      renal vascular resistance. Studies in children are less numerous than in adults.
      The main findings of the studies on renal reserve in children have disclosed the
      following: (1) the lack of an age dependency, (2) the normalcy of renal reserve
      in renal disease, (3) the return of renal reserve in type 1 diabetes mellitus by
      a reduction in protein intake, and (4) the suppressibility of renal reserve by
      somatostatin infusion.

PMID- 8525149
TI  - Renal reserve in the elderly.
AB  - The increase in glomerular filtration rate after an amino acid load, the so
      called renal reserve, was found to be impaired in the aged rat. Renal diseases
      progress more rapidly in the elderly. Whether the renal reserve predicts
      progression of renal disease is controversial, however, and generally little
      information on renal reserve in elderly subjects is available. We examined renal
      hemodynamics before and after an amino acid infusion in 15 healthy normotensive
      subjects of young age (median age, 26 years [23 to 32]) and in 10 of old age (70
      years [61 to 82]). Median basal inulin (Cin) and paraaminohippurate (Cpah) steady
      state clearances were significantly lower in the elderly (102 and 339 mL/min/1.73
      m2) than in the young subjects (122 and 647 mL/min/1.73 m2), but virtually all
      GFR values of the elderly were still within the normal range. The median percent
      rise of Cin was +16% in young and +17% elderly subjects (independent of gender).
      A well-preserved renal reserve was also confirmed by two other studies; one in
      chronically ill elderly patients treated for various nonnephrological diseases
      using an amino acid load and the other in healthy elderly volunteers in which
      renal reserve was tested with a protein (meat) meal. The mean absolute renal
      reserve in the three cohorts studied was between 16 and 26 mL/min/1.73 m2, the
      oldest patient studied was 89 years. The results of these studies document that
      in humans renal functional reserve is preserved at least until age 90 years in
      women and men.

PMID- 8525150
TI  - Renal reserve in patients with solitary kidneys.
AB  - The first part of this article focuses on the risk of functional deterioration in
      subjects with solitary kidneys; the long-term clinical outcome of various
      subgroups of patients is reviewed. Thereafter, the pathophysiology of the renal
      functional reserve in subjects with a 50% reduction in renal parenchyma and the
      results coming from studies eliciting the renal reserve in these subjects are
      summarized. Finally, the clinical significance of the renal functional reserve
      and its usefulness in clinical practice are critically discussed.

PMID- 8525151
TI  - Renal functional reserve in subjects with diabetes mellitus.
AB  - Diabetic nephropathy develops in approximately 35% of patients with insulin
      dependent diabetes mellitus (IDDM) and in a similar proportion of patients with
      non-insulin-dependent diabetes mellitus (NIDDM). However, we remain at present
      unable to identify the susceptible subset prior to the development of
      microalbuminuria. Up to 25% of IDDM patients and a variable proportion of NIDDM
      patients manifest glomerular hyperfiltration in the first few years of diabetes.
      It has been debated whether this basal hyperfiltration is predictive of future
      renal disease and whether better prediction can be achieved by the use of the
      renal haemodynamic response to a protein meal, defined by some authors as renal
      reserve. The concept of renal functional reserve in patients with diabetes
      mellitus is complicated by the dependence of the GFR response on basal GFR, the
      influence of the prevailing metabolic conditions, and because the response
      differs to different stimuli. We review the factors affecting renal hemodynamics
      and renal hemodynamic responses in the context of supranormal, normal, and
      impaired renal function in diabetes. We conclude that although the measurement of
      renal functional reserve may help clarify important pathophysiological
      mechanisms, the assessment of basal GFR in clinical practice is all that is
      required for predictive and monitoring purposes.

PMID- 8525152
TI  - Renal reserve in patients with high blood pressure.
AB  - The mechanism by which hypertension produces renal damage remains poorly defined.
      Experimental evidence suggests that glomerular hypertension/hyperfiltration
      constitutes a potential mechanism by which hypertension leads to chronic renal
      failure. Renal functional reserve has been used to investigate the presence or
      absence of hyperfiltration, both in experimental animals and humans.
      Micropuncture studies using the two-kidney, one-clip hypertension model have
      shown that glomerular hypertension/hyperfiltration is associated with loss of
      renal functional reserve. However, loss of renal functional reserve in this
      experimental model is not always indicative of hyperfiltration because some
      antihypertensive agents (Verapamil, Losartan) correct glomerular
      hypertension/hyperfiltration, but do not restore renal reserve. Renal reserve has
      also been evaluated in patients with essential hypertension. Some investigators
      have shown that hypertension is associated with loss of renal functional reserve
      which can be restored in some studies with antihypertensive therapy. However,
      normal renal reserve has also been shown in hypertensive patients. Altogether,
      these data suggest that renal functional reserve cannot be used to assess the
      role of hemodynamic mechanisms in hypertension-induced renal injury. Long-term
      follow-up studies are required to establish if loss of renal reserve is
      indicative of risk factors leading to renal failure in patients with systemic
      hypertension.

PMID- 8525153
TI  - [Cerebrovascular accidents and AIDS].
AB  - A number of pathological and clinical data suggest that AIDS could be an
      underestimated cause of cerebro-vascular disease, especially in young
      individuals. Eight retrospective cases of stroke in AIDS patients are reported.
      Mean age was 39 years, mean CD4 cells count 57/mm3. Pathogenic mechanism,
      particularly the role of opportunistic infections remains unclear. Prognosis does
      not seem constantly pejorative: only one patient died from stroke, six are still
      alive with a 6 months follow-up, without relapse and with minor or no sequellae.
      Alcohol or cocaine (crack) abuse was present in half the cases. The role of
      specific risk factors and consequently adapted prophylaxis is questionned.

PMID- 8525154
TI  - [Mycobacterium kansasii infection in patients with human immunodeficiency virus
      infection].
AB  - We report a retrospective study of 12 caucasian men infected with HIV who had
      developed Mycobacterium kansasii infection (Mk). All patients had a low blood
      lymphocyte CD4 count (1-130, mean 15/mm3) and ten met the diagnostic criteria for
      AIDS. The 12 patients had pulmonary symptoms (dyspnea, cough) and fever. On chest
      X-ray, nodular, interstitial or diffuse parenchymal infiltrates, mediastinal and
      hilar adenopathies were observed. Two patients had pleural effusion, but none had
      cavitary lung disease. Mk was isolated by culture of sputum (n = 7), blood (n =
      3), bronchial biopsy (n = 2) or bone marrow (n = 1). No patient had clinical
      extra-pulmonary disease. Survival after diagnosis was in average 7 months.
      Potential for therapeutic response is reviewed and documented.

PMID- 8525155
TI  - [Drug-induced hepatitis: epidemiologic, clinical, diagnostic and physiopathologic
      aspects in 1995].
AB  - Drug-induced hepatotoxicity is a major cause of iatrogenic diseases. More than
      900 compounds, including herbal medicines are involved and can reproduce the full
      spectrum of liver injuries. Acute hepatitis are the most frequently observed.
      Three types are described: acute hepatocellular hepatitis which are frequently
      similar to viral hepatitis, and can lead to fulminant liver failure and death
      within a few days, or, more insidiously, to cirrhosis; acute cholestatic
      hepatitis, which exhibits a better prognosis, may be misleading by mimicking
      biliary obstruction; mixed-pattern hepatitis, which associates features of
      hepatocellular and cholestatic hepatitis. Acute hepatitis generally exhibits no
      specific patterns. Then, the diagnosis is difficult and relies upon the
      elimination of other causes and a compatible or a suggestive time-relationship
      between drug ingestion and the onset of hepatitis as well as between drug
      withdrawal and recovery. Sometimes, drug hepatotoxicity is suggested by the
      association of hepatitis to hypersensitivity manifestations (hypereosinophilia),
      to some histopathological features (eosinophilic infiltration, microvesicular
      steatosis, giant hepatocytes) or, more uncommonly, to specific autoantibodies
      (anti-mitochondrial type 6, anti-LKM2, anti-LM antibodies). Cross hepatotoxicity
      may occur between drugs having related chemical structures.

PMID- 8525156
TI  - [Evaluation of tumor response during chemotherapy of bronchial cancer].
AB  - Chemotherapy of lung cancer is still an experimental approach requiring careful
      evaluation. Tumour response (marker of anticancer activity) is not perfectly
      correlated to survival (marker of chemotherapy efficacy), but its evaluation
      remains a milestone inasmuch as reporting a wrong tumour response rate might lead
      to the rejection of active new treatments. This review deals with the method of
      tumour response measurements and its use during a chemotherapy protocol.
      Recommendations drawn from the analysis of the literature are: 1) to assess and
      classify all lesions which can be identified at the beginning of the treatment;
      2) to define the target lesions, mainly the ones which can be bidimensionally
      measured; 3) to use the World Health Organization recommendations for reporting
      the overall response; 4) to confirm complete response by negative rebiopsies; 5)
      to avoid second fiberoptic bronchoscopy to patients with stable or progressive
      disease on CT-scan, and finally; 6) to assess response quality by evaluating
      response duration and improvement of quality of life.

PMID- 8525157
TI  - [Disseminated histoplasmosis: 2 cases in patients with human immunodeficiency
      virus infection in French Guiana].
AB  - The authors report two cases of disseminated histoplasmosis occurring in HIV
      infected patients living in French Guiana. The first case was an acute
      disseminated histoplasmosis with a rapid fatal evolution. The second case was
      diagnosed on a mucosal localisation, and improved under itraconazole therapy.
      These two cases show the diversity of the clinical course of this opportunistic
      infection. The authors focus on the difficulty of the diagnosis and the need for
      direct microscopic examination to identify histoplasma and to enable a swift
      therapeutic intervention.

PMID- 8525158
TI  - [Adrenal histoplasmosis in a non-insulin-dependent diabetic patient].
AB  - Adrenal histoplasmosis is a rare infection that can be misdiagnosed as
      tuberculosis. We present here a case of adrenal histoplasmosis in a 65 year-old
      male diabetic with marked weight loss. Laboratory investigations noticed an
      inflammatory syndrome and the abdominal computed tomography scanner reported an
      heterogenous left adrenal mass of 6 cm in diameter. Hormonal as well as
      bacteriological studies were negative. The patient was operated and the
      histopathological examination proved that the mass was a tuberculoma and an anti
      tuberculous treatment was started. Four months later, the patient suffered from
      recurrence of symptoms and laboratory investigations confirmed the inflammatory
      syndrome and the abdominal computed tomography scanner showed a right adrenal
      mass. A surgical biopsy was performed and specific fungal researches proved that
      the lesion was due to Histoplasma capsulatum. The patient experienced a
      remarkable improvement under anti-fungal treatment.

PMID- 8525159
TI  - [Stauffer's syndrome disclosing kidney cancer: another cause of inflammatory
      syndrome with anicteric cholestasis].
AB  - Stauffer's syndrome is characterized by a cholestasis without biliary obstruction
      or hepatic metastasis and a renal tumor. We report a case of Stauffer's syndrome
      in a 73 year-old woman. Cholestasis and inflammatory syndrome regressed with
      corticosteroid. Giant cell arteritis with negative temporal artery biopsy was
      wrongly suspected.

PMID- 8525160
TI  - [HLA DRB1 polymorphism in rhizomelic pseudo-polyarthritis and Horton disease].
AB  - Some studies have suggested that distribution of HLA DRB1 alleles in polymyalgia
      rheumatica (PMR) resembles that found in giant cell arteritis (GCA). However
      these data are controversial. OBJECTIVE--To evaluate in French native patients
      whether PMR immunogenetically resembles GCA in determining HLA DRB1 alleles.
      PATIENTS AND METHODS--Fourty-five patients were included in the study. Twenty-one
      patients with PMR alone (Bird's criteria) and 24 with GCA (ACR criteria). In 11
      patients, GCA was associated with PMR. HLA DRB1 genotype was determined by PCR
      RFLP analysis. Statistical analysis was performed by the chi 2 test and
      determination of the odds ratio (OR). Two hundred and thirty-three unselected
      normal healthy subjects served as controls. RESULTS--A significant increased
      prevalence of HLA DR1 was observed in patient with PMR alone and an absence of
      DR7 (0% vs 10.3%, p = 0.02, OR = 0.1). An increased incidence of DR4 and
      particularly *0401 allele was only found in patients with GCA (OR = 2.4). No
      patient with isolated PMR had DR7 genotype compared with 25% in GCA (p < 0.001,
      OR = 0.03). A comparative study between isolated PMR versus GCA showed a
      significant increased in DR1 and DR3 alleles in isolated PMR and a significant
      increased prevalence of DR4 and DRB1 *0701 allele in GCA. CONCLUSION--The present
      study emphasizes the absence of similarity in HLA DRB1 allele distribution
      between PMR and GCA. The association of DR7 in patient with GCA seems
      characteristic in French native patients.

PMID- 8525161
TI  - [Colchicine: recent data on pharmacokinetics and clinical pharmacology].
AB  - Colchicine is widely used in the treatment of acute goutty arthritis. Recently,
      colchicine was shown to be effective in inflammatory diseases such as familial
      Mediterranean fever. Two proteins can modulate its pharmacokinetics: tubulin, the
      specific intracellular receptor for colchicine which determines the plasma half
      life, and P-glycoprotein, an active efflux pump towards some anticancer drugs
      which regulates colchicine absorption, distribution, and elimination. Therapeutic
      dosage is monitored empirically, by the control of the balance between the
      occurrence of side effects and the clinical efficacy. Recently, using a specific
      and sensitive radioimmunoassay, the investigation of plasma concentrations during
      single and multiple dose studies has allowed to define the colchicine
      pharmacokinetic parameters. Following oral route, colchicine bioavailability is
      extremely variable (from 24 to 88% of the administered dose), the distribution
      volume is elevated (7 l/kg) but the binding to albumin is moderate. Colchicine
      elimination occurred mainly via hepatic pathways and the elimination half-life
      ranged from 20 to 40 hours. In multiple dose study (1 mg/d), the steady-state is
      reached 8 days after the first oral administration and plasma concentrations
      ranged from 0.3 to 2.5 ng/ml. Pharmacokinetic/pharmacodynamic studies show that
      the biological effects of colchicine were not related to plasma concentrations
      but with intraleukocyte concentrations. Drug interactions may occur when
      colchicine is associated to drugs which interact with cytochrome P450 and/or P
      glycoprotein and modify renal and/or hepatic clearances. The therapeutic drug
      monitoring of colchicine during these circumstances could allow to prevent the
      observation of side effects.

PMID- 8525162
TI  - [Reversed electrophoresis].

PMID- 8525163
TI  - [Herpes zoster ophthalmicus and oculomotor involvement].

PMID- 8525164
TI  - [Acute brucellosis with uncommonly long incubation].

PMID- 8525165
TI  - [Nifedipine reduces the increase of free intracellular calcium in primary
      hyperparathyroidism: role of calcium channels and PTH].
AB  - Free intracellular calcium is increased in primary hyperparathyroidism (HPT) and
      may be related to the higher incidence of hypertension in this disease. This
      elevation returns to normal when primary HPT is corrected. In essential
      hypertension, an alteration in calcium channels allows a intracellular
      accumulation of calcium. Aiming to asses if a similar mechanism operates in
      primary HPT, we measured intracellular calcium concentrations using QUIN-2-AM,
      before and after a 10 mg sublingual dose of nifedipine, in 9 subjects with
      primary HPT, 12 subjects with essential hypertension and 17 normal controls.
      Intracellular calcium was higher in subjects with primary HPT and with essential
      hypertension than in normal controls (276 +/- 56, 343 +/- 50 and 113 +/- 12 nM
      respectively). Among patient with primary HPT, intracellular calcium correlated
      with plasma PTH (r = 0.82). Nifedipine reduced intracellular calcium to 173 +/-
      36 nM in subjects with primary HPT and to 188 +/- 35 nM in those with essential
      hypertension. In the latter, the decreased in intracellular calcium and blood
      pressure correlated significantly (r = 0.65 p < 0.03). We conclude that increased
      intracellular calcium in primary HPT and essential hypertension seems to depend
      on an increased inflow through specific channels. However in primary HPT, this
      alteration is related to PTH levels.

PMID- 8525166
TI  - [Cellular and molecular differences in cleft palate susceptibility in mice].
AB  - The aim of this study was to identify possible candidate genes for the
      susceptibility to cleft palate. We studied hyaluronic and glycoprotein levels
      with morphometric and histochemical techniques, in palatine processes of 13 and
      14 days old mouse embryos of strains A/Sn and C/57 BL, that are respectively
      susceptible and resistant to glucocorticoid and non steroid anti-inflammatory
      drug induced cleft palate. At 13 days, in palatine processes of the resistant
      strain and when these are still vertical, there was a significantly higher amount
      of extracellular matrix, constituted principally by hyaluronic acid. These
      differences disappeared at 14 days, when the processes became horizontal. The
      basal membrane of the medial palatine epithelium of the susceptible strain,
      showed interruptions due to a lower amount of glycoproteins. It is concluded that
      the observed differences in the amount and quality of these molecules, are a
      consequence of genetic differences that could determine the susceptibility to
      cleft palate.

PMID- 8525167
TI  - [Enzymatic mechanisms of resistance to aminoglycoside antibiotics in gram
      negative bacilli from Chilean hospitals].
AB  - The presence of aminoglycoside modifying enzymes (AMEs) has been investigated, by
      an agar diffusion method, in 344 strains of aminoglycoside-resistant Gram
      negative bacilli isolated in different Chilean hospitals. Most of the strains
      exhibited a combination of enzymatic mechanism of resistance, but two acetylating
      (AAC(3)II and AAC(6')I) and one phosphorylating (APH(3')I) enzymes were the main
      mechanism detected in the strains. A significant increase in the frequency of
      strains producing AAC(6')I, possible due to wide use of amikacin, has been found
      when results were compared with those of a report published in 1985.

PMID- 8525168
TI  - [Epidemiological and etiological aspects of upper digestive hemorrhage.
      Multicenter study in nine Chilean hospitals (1980-1990)].
AB  - An epidemiological survey about the incidence of upper gastrointestinal bleeding
      during three periods (1980, 1985 and 1990), was performed in 9 Chilean hospitals.
      Its annual incidence decreased in 1990, when compared to 1980. Likewise the
      etiologies changed, with an increase in the incidence of duodenal ulcers and a
      decrease in the incidence of erosive gastritis and bleeding of unknown origin in
      1990. A seasonal variation with higher bleeding rates in autumn was also
      recorded.

PMID- 8525169
TI  - [Geographical distribution of physicians in Chile].
AB  - In 1994, Chile had 15,451 active physicians (less than 70 years old) for a
      population of 14,027,344 with a ratio of 1 physician per 908 inhabitants, a
      satisfactory figure compared to other countries of similar socio-economical
      development. Ratios of 1:880 and 1:843 are projected for 1999 and 2004
      respectively. The annual rate of physician's population growth (2.2%), that is
      superior to the general population's growth rate (1.6%), will increase to about
      2.5% per annum in 2001 as a consequence of the creation of three new medical
      schools. However, the distribution of physicians along the country is
      unsatisfactory. While the capital (Metropolitan Region) has a ratio of 1
      physician per 629 inhabitants, the figure for the Region of Maule is 1:2,113.
      Only two of ten regions, excepting the capital, have a ratio lower than 1:1,000.
      Sixty percent of physicians live in Santiago while only 40% of the general
      population does so, illustrating their high concentration. Median ratio in Chile,
      that better reflects the reality than the mean, is 1:1,280. The heterogeneous
      distribution of physicians in Chile is a sign of social inequity that must be
      corrected. In a free society a better physician distribution is achieved with
      economical and professional incentives given by health institutions.

PMID- 8525170
TI  - [Imipenem/cilastatin versus ceftazidime-amikacin in the treatment of febrile
      neutropenic patients].
AB  - AIM: To compare the efficacy of imipenem/cilastatine and ceftazidime-amikacin in
      the treatment of febrile neutropenic patients. DESIGN: Open, prospective and
      randomized clinical study. PATIENTS: Fifty two patients (26 female) aged 16 to 80
      years old with 60 episodes of neutropenia were studied. They were randomly
      assigned to receive imipenem/cilastatine in doses of 500 mg iv qid or the
      combination of ceftazidime 1 to 1.5 g iv tid and amikacin 7.5 mg/kg iv bid.
      RESULTS: Global response to initial therapy was 53% in patients receiving
      imipenem/cilastatine and 37% in those receiving ceftazidime-amikacin (p = ns).
      When other antimicrobial were added, a 90 and 85% infection eradication success
      was achieved respectively. Six febrile episodes in the group receiving
      imipenem/cilastatine and 12 episodes in the group receiving ceftazidime-amikacin
      had Gram positive cocci as the sole infectious agent (p < 0.04). A lower duration
      of neutropenia had a favorable influence on treatment outcome. Three patients
      receiving imipenem/cilastatine (10%) and four receiving ceftazidime-amikacin
      (13%) died. Superinfections and toxicity related to antibiotics were minimal in
      both groups. CONCLUSIONS: Imipenem/cilastatine and the combination of ceftazidime
      with amikacin were equally effective in the treatment of febrile episodes in
      neutropenic patients.

PMID- 8525171
TI  - [Coloanal anastomosis (Parks operation) in the treatment of acute radiation
      rectitis].
AB  - AIM: To assess immediate and late results of Parks operation in the treatment of
      severe radiation rectitis. PATIENTS AND METHOD: Retrospective review of clinical
      histories of 35 patients with uterine cervical cancer, 5 with endometrial cancer
      and one with vaginal cancer that received radiotherapy. Two years as a mean after
      radiotherapy, 14 women had rectal bleeding, 19 fistulae, 7 stenosis and 1 a
      rectal ulceration. All were initially treated with a discharge colostomy and
      after a mean interval of 1.6 years, a Parks operation was performed. RESULTS: One
      patient died after surgery (2.4%) due to peritonitis and sepsis. Early surgical
      complications were necrosis of descended colon in 2, intra-abdominal abscess in
      1, splenic rupture in 1 and postoperative bleeding in 1. Colostomy was closed in
      37 patients three months after surgery. During late follow up (ranging from 3 to
      64 months) rectal continence has been assessed as good in 30 patients, fair in 5
      and bad in 2. Three women required a new colostomy. CONCLUSION: Parks operation
      is a viable therapeutic alternative for severe radiation rectitis.

PMID- 8525172
TI  - [Apomorphine test: evaluation of dopaminergic response in patients with Parkinson
      disease].
AB  - Apomorphine is a potent dopaminergic agonist that quickly and predictably reverts
      parkinsonian symptomatology. In 32 patients (18 male) aged 45 to 83 years old (22
      with idiopathic parkinsonism and 10 with parkinsonism of other causes), the
      dopaminergic response to apomorphine after domperidone administration was
      assessed using the digital skill test and Webster scale. Twenty patients with
      idiopathic parkinsonism and 1 with parkinsonism of other causes had a positive
      response to apomorphine. In 44% apomorphine had adverse effects. All patients
      with idiopathic parkinsonism and the only patient with parkinsonism of other
      causes with a positive apomorphine test had a good response to levodopa therapy.
      It is concluded that apomorphine test has a 95% positive predictive value for
      idiopathic parkinsonism and is a useful diagnostic tool.

PMID- 8525173
TI  - [Detection of fecal Cryptosporidium parvum antigens using an ELISA technique].
AB  - ELISA techniques using monoclonal antibodies have been recently developed for the
      detection of Cryptosporidium parvum fecal antigens. The aim of this work was to
      compare the yield of these ELISA techniques with Ziehl-Nielsen and Safranin
      stains in formaldehyde-salt fixed samples. One hundred five fecal samples of
      patients with acute diarrhea were studied. Forty-seven samples did not contain
      Cryptosporidium and ELISA was negative. Also, ELISA was positive in 52 or 58
      samples that contained Cryptosporidium (89.6%); the samples with false negative
      results contained scanty oocysts. Seven intensely positive Paf-fixed stool
      samples from AIDS patients with chronic diarrhea, were not reactive to ELISA.
      There was a good correlation between visually and mechanically read samples and
      there were no false positives. It is concluded that ELISA cannot be used in Paf
      fixed samples and has a lower sensitivity that the stained commonly used for the
      diagnosis of cryptosporidiosis.

PMID- 8525174
TI  - [Unusual presentation of urinary tract infection in 6 cases].
AB  - Urinary tract infections may have different clinical presentations that may range
      from asymptomatic bacteriuria to purulent collections and severe sepsis. We
      report 6 diabetic patients, 3 presenting with a renal carbuncle and 3 with an
      emphysematous pyelonephritis. All required medical and surgical treatment and had
      a good evolution. Two carbuncles were caused by beta- hemolytic type B
      streptococcus. This is the second notification of this agent as causative of
      renal abscesses, probably reaching the kidney through hematogenous dissemination
      from cutaneous foci.

PMID- 8525175
TI  - [Hypocorticism due to selected deficiency of CRH with spontaneous resolution. A
      case report].
AB  - Hypocortisolism derived from hypothalamic deficiency of corticotropin releasing
      hormone is a highly unusual cause of adrenal insufficiency, and its pathogenesis
      is still not fully understood. We report a mildly symptomatic patient having
      repeated low basal plasma cortisol levels with normal cortisol response to ACTH
      and Lysine-vasopressin; however, she showed a clearly limited response to deep
      hypoglycemia, while GH reached a normal concomitant response. After 7 years of
      cortisol replacement the endogenous cortisol returned spontaneously to normality.
      The rest of pituitary function has been always normal.

PMID- 8525176
TI  - [Hypothenar hammer syndrome].
AB  - Hypothenar hammer syndrome is an infrequently diagnosed labor disease. We report
      a 51 years old male who used the medial aspect of his left hand as a hammer over
      the past 12 years. He presented with an ipsilateral ring finger embolization. An
      angiogram demonstrated an ulnar artery occlusion at the hypothenar eminence. No
      other source of emboli was found and treatment was conservative. This disease is
      a consequence of repetitive trauma on the ulnar artery, that leads to vessel wall
      changes and promotes local thrombosis, distal embolization and eventually,
      occlusion in situ. Treatment options are conservative in case of occlusion or
      reconstruction with exclusion of the emboligeneous area.

PMID- 8525177
TI  - [Cushing's syndrome: review of a national caseload].
AB  - Cushing's syndrome occurs rarely; in analyzing 50 cases studied at our
      institution we discuss the following aspects: syndromatic diagnosis, etiologic
      differentiation into the 3 categories of the syndrome, and therapeutic strategies
      for each variety. We postulate that non-endocrinologists should be responsible
      for the syndromatic diagnosis, easily done by using 2 simple tools: the
      measurement of basal free urinary cortisol and the performance of an overnight
      suppression of the adrenal axis with 1 mg of dexamethasone (Nugent's test). In
      contrast, the etiologic diagnosis and the therapeutic interventions should be
      strictly restricted to highly specialized institutions having well seasoned
      endocrinologists, a reliable endocrine laboratory, easy access to computed
      tomographies of the brain and abdomen as well as to nuclear resonance imaging of
      the brain. The usefulness of our in-house devised vasopressin challenge following
      overnight dexamethasone suppression for the etiologic diagnosis is highlighted.
      Neurosurgical expertise in the transsphenoidal approach to the pituitary gland as
      well surgeons well experienced in adrenal surgery are a must to offer a
      reasonable chance of success to patients with the syndrome. Forty one (82%) of
      the series were female patients, 78% were pituitary-dependent and 22% pituitary
      independent Cushings. Six out of 8 (75%) of the adrenal tumors were carcinomas.
      Only 3 patients (6%) qualified as ectopic ACTH syndromes. The easiest variety to
      diagnose and treat was the adrenal adenoma (2 cases); adrenal carcinomas were
      always incurable. The ectopic ACTH syndrome was amenable to successful medical
      treatment with ketoconazole or surgical resolution with complete resection of the
      offending tumor (1 of 3 cases) or bilateral adrenalectomy (2 of 3 cases)
      Pituitary-dependent Cushings are quite tricky to diagnose and difficult to treat.
      Transsphenoidal resection of the offending microadenoma was successful in only
      43.5% (10/23) of cases and we experienced 3 recurrences of the syndrome even
      after 8 years of successful removal of the pituitary adenoma. The remainder had
      to be cured by bilateral adrenalectomy. Seven out of 39 patients with Cushing's
      disease (18%) ultimately died for a variety of reasons; six out of 6 patients
      (100%) with adrenal carcinoma died of dissemination; two out of 2 adrenal
      adenomas cured and 1 out of the 3 ectopic ACTH syndromes died of dissemination of
      a malignant thymic carcinoma. We conclude that Cushing's syndrome is a serious,
      underdiagnosed disorder, which should be suspected and diagnosed by the non
      specialized physician and then referred to a specialized center for expert
      etiologic diagnosis and surgical therapy.

PMID- 8525178
TI  - [Introduction to bioethics in contemporary medicine].
AB  - The author makes a historical revision of his 50 years experience in medical
      ethics as a student and physician. In 1944, medical ethics was traditional and
      resolved simple problems based on Hippocrates postulates and christian humanism.
      The present scientific and cultural revolution has impelled the rise of bioethics
      defined as "the systematic study of human behavior in life sciences, based on
      moral principles". The bioethical methods attempt to facilitate the application
      of universal ethical principles to the solution of complex cases, generated by
      the new medical technology. These ethical problems were posed in Chile in 1962 by
      the french professor Jean Cheymol, who reported the serious human rights abused
      derives from new scientific experiments. Later in 1973, Dr. Motulsky predicted
      the advent of "a brave new world" and the need to create a new biological ethic.
      These challenges were faced by the professors of the faculty of Medicine, who
      created ethics commissions in 1975 and edited medical ethics code texts. There
      are three players in the bioethic context. Physicians apply beneficence; patients
      defend their autonomy: the State and the society defends justice. A conflict of
      values lies in the bottom of bioethics. The author vindicates the coherence of
      traditional medical ethics. Philosophers, theologians and lawyers can only help
      physicians, but are not responsible. Bioethics must allow a frank dialogue
      between these professionals, respecting their roles and responsibilities.

PMID- 8525179
TI  - [Reproductive health in adolescent students: knowledge, attitudes, and behavior
      in both sexes, in a community of Santiago].
AB  - Nine hundred forty eight teenagers (600 females) from a public school of one of
      the poorest communities of Santiago were surveyed about knowledge and practices
      on sexuality and reproductive health. Twenty four percent of females and 40% of
      males did not talk about their problems at home, instead they talked
      preferentially with their friends. Half of the sample attributed a risk a
      pregnancy to the first sexual intercourse; 67% did not know the infertile phase
      of the menstrual cycle and 20% did not identify two sexually transmitted
      diseases. Sixty percent considered rhythm technique as a safe fertility control
      method, 60% of males and 50% of females considered masturbation as risky, 57% of
      males and 49% of females estimated that condoms could be reused and between 5 and
      16% of the sample correctly identified AIDS modes of transmission. Fifty percent
      had a couple and 23% of males and 17% of females had a sexual intercourse in the
      last six months; of these, 45% of women and 27% of men used a contraceptive
      method. Four percent of women and 6% of men became involved in a pregnancy and
      57% of these terminated in abortions. It is concluded that knowledge about
      sexuality and reproductive biology among low income teenagers is scanty.

PMID- 8525180
TI  - [The one thousand faces of pain].

PMID- 8525181
TI  - [Health, smoking, and physicians].

PMID- 8525182
TI  - [Eponyms: should they be used in medicine?].

PMID- 8525184
TI  - [Reflections on primary health care for adults].

PMID- 8525183
TI  - [Chilean medicine immediately after the 1891 revolution].
AB  - The conflict between the Chilean President Balmaceda and the parliament lead him
      to rule the country despotically during 8 months, until his suicide in 1891.
      During this lapse he persecuted and imprisoned his opponents, including several
      Medical School professors. Doctor David Benavente, professor of Anatomy and
      Balmaceda's opponent, wrote a chronicle at the Revista Medica de Chile (1897;
      20:46) referring to the changes that occurred at the Medical School: "Flogged by
      dictatorship's winds, it barely gave sings of life during the eight months that
      Balmaceda dominated the country". Political passion almost annihilated for ever
      the first scientific teaching center of the University of Chile, posed a project
      at the Public Instruction Council "to create in all high schools a special class
      about the general principles of the Constitution". Once democratic normality was
      re-established, the development of Chilean Medicine was greatly impelled, sending
      young physicians to specialize at qualified european centers.

PMID- 8525185
TI  - [Impact of outdoor pollution on indoor air quality. The case of downtown Santiago
      (Chile)].
AB  - The influence of outdoor pollution on indoor air quality was studied in downtown
      Santiago(Bandera street). Carbon monoxide (CO), nicotine, particulate matter,
      respirable fraction (PM5) and total and carcinogenic polyaromatic hydrocarbons
      (PAHs) were simultaneously monitored indoors and outdoors in restaurants, offices
      and other places. The levels of CO changed simultaneously outdoors and indoors (r
      = 0.89) specially during traffic rush hours, demonstrating the importance of
      outdoor infiltration into the indoor air quality and masking the contribution of
      other CO indoor sources. The maximum CO concentrations were over 800% and over
      1000% higher indoors and outdoors respectively than the 9 ppm CO National Ambient
      Air Quality. The PM 5 concentrations were very high and showed no significant
      differences (p > 0.05) from indoors to outdoors, or between indoor levels in
      restaurants, offices and other places. Total and carcinogenic PAHs levels were
      also very high outdoors and indoors, outdoor levels being generally higher than
      those indoors and no significant; differences (p > 0.05) were found for the
      indoor levels between restaurants, offices and other places. Nicotine levels
      showed significant differences (p < 0.05) between indoor and outdoor levels. In
      addition, great differences (p < 0.05) in indoor levels, were found between
      offices and restaurants, and offices and other places. Among indoor sources
      cigarette smoke seems to be a minor source since nicotine concentrations, being
      2.3 times higher in restaurants and other places than in offices, do not
      contribute to enhance significantly PM5 and total and carcinogenic HAPs in the
      first ones. These results suggest that in downtown Santiago, infiltration might
      be the main source of indoor pollution. This is supported by two evidences: a)
      coronene, a tracer of vehicle emissions was found in high concentration indoors
      and b) in restaurants (in which PAHs emissions might be higher indoor) a
      correlation coefficient of 0.987 for the indoor and outdoor concentrations of
      carcinogenic PAHs was found. Furthermore a survey asking for different symptoms
      and effects probably related to air pollution was made to people working in
      Bandera and in a rural area located 40 Km from Santiago. The results showed that
      excluding smoking as a confoundend factor, people working in Bandera showed a
      significantly greater (p < 0.05) risk of ill effects on their health than people
      working in the rural area.

PMID- 8525186
TI  - [Migration and health. Social and medical consequences of exile and
      repatriation].
AB  - Three hundred thirty eight Latinamerican refugees living in Lund, Sweden, 51 that
      lived in Lund and were repatriated to Chile and 1132 Swedish subjects were
      interviewed using the survey of the Swedish National Statistics Institute. Data
      were analyzed using an unconditional logistic regression model, controlling
      possible confounders. Refugees living in Lund and repatriated to Chile considered
      their health as bad in a higher proportion than their Swedish counterparts, with
      an odds ratio of 3.48 (2.03-5.66) and 4.78 (2.1-10.25) respectively. Refugees and
      repatriated subjects had a higher risk of suffering long lasting illnesses with
      odds ratio of 2.84 and 2.64 respectively. It is concluded that there are great
      differences in life standards, housing and social relationships between Swedish
      people, Latinamerican refugees and repatriated individuals.

PMID- 8525187
TI  - [Hepatitis C virus: results of detection in several high risk groups in the X
      region of Chile].
AB  - The aim of this study was to determine the prevalence of hepatitis C virus
      antibodies in high risk patients coming from Valdivia, Osorno and Puerto Montt.
      Fifty-six patients in hemodialysis, 51 renal graft recipients, 42 cirrhotics and
      14 patients with acute non A non B hepatitis were studied. Antibodies were
      detected with a second generation ELISA technique and positive cases were
      confirmed with RIBA. All hemodialysis patients and renal graft recipients were
      negative for hepatitis C virus antibodies. In one non alcoholic patient with
      cirrhosis, a positive ELISA was confirmed with RIBA. Six patients with acute
      hepatitis had positive ELISA tests but none was confirmed with RIBA. It is
      concluded that the prevalence of hepatitis C virus antibodies in this region of
      Chile is very low.

PMID- 8525188
TI  - [Blunt trauma of the liver: treatment and results in 45 patients].
AB  - We report a retrospective analysis of 45 patients (41 male) aged between 14 and
      57 years, with a blunt liver trauma seen between 1984 and 1993. Sixty two percent
      had complex liver lesions and 73% extraabdominal injuries. Peritoneal lavage and
      abdominal ultrasound appeared as useful diagnosis tools. Five patients were not
      operated and had a satisfactory evolution. Among operated patients, liver lesions
      were corrected with simple measures in 60%, hepatotomy in 7.5% and resection in
      17.5%. As additional measures, tamponade was used in 4, resuscitation thoracotomy
      in 4, porto caval shunt in 2 and Marimoto balloon in 1. Eighteen percent of
      patients died and 32% had postoperative complications.

PMID- 8525189
TI  - [Erythropoietin and transfusions in patients with anemia of chronic renal failure
      origin : an update view].
AB  - Aiming to know the factors that influenced the use of erythropoietin (EPO) in
      chronic hemodialysis patients, we retrospectively studied 82 patients (41 male),
      of whom 15 received EPO. No differences, between patients receiving or not
      receiving EPO, were found in age (46.9 +/- 25 and 57 +/- 13 years respectively),
      male/female ratio (9/6 and 32/35 respectively), time on dialysis (36.4 +/- 25.6
      and 36.8 +/- 31.8 months respectively), dialysis hours (3.19 +/- 0.6 and 3.33 +/-
      0.39 h respectively) and proportion of diabetics (6.6 and 20.8% respectively).
      Prior to EPO use and compared to untreated patients, treated patients were
      transfused with a higher frequency (60 vs 22%) and with more units/patients/years
      (0.12 vs 0.08). Hemoglobin levels at the start of the treatment was similar in
      treated and untreated patients (8.4 +/- 1.46 vs 8.78 +/- 1.97 g/dl). EPO was
      indicated in 11 patients due to general symptomatology associated to anemia and
      in 4 due to cardiac failure or angina. We conclude that EPO treatment is
      indicated in approximately 18% of patients in dialysis. An adequate dialytic
      treatment may achieve optimal hemoglobin levels with minimal transfusion
      requirements and without need of EPO, thus reducing costs.

PMID- 8525190
TI  - [Chronic intermittent peritoneal dialysis: a 12-year experience].
AB  - Since 1981, we have treated 46 adults aged 56 +/- 21 years, of whom 17 were
      diabetic, with intermittent peritoneal dialysis. Their mean time on dialysis has
      been 21 months with an accumulated experience of 493 months/patient. The program
      included 2 dialyses per week, 25 exchanges of 21 per session and 30 min of dwell
      time. Arterial pressure control has been satisfactory. Diabetic patients had
      lower levels of serum calcium, alkaline phosphatases and m-PTH. The incidence of
      peritonitis has been 1 episode/14 months/patient and the causative agent has been
      Staphylococcus aureus in 47% of episodes. Mean catheter duration has been 15
      months and 1 episode/34 months/patient of exit site infection has been recorded
      and Staphylococcus aureus has been the causative agent in 83% of episodes. The
      risk of acquiring the first peritonitis was 12% at 3 months, 23% at 6 months and
      higher for non diabetic patients. Actuarial survival of treated patients at 12
      and 24 months was 89 and 67% respectively. No differences in survival were
      recorded between diabetic and non diabetic patients. Fifty two percent of
      patients that dropped out continued on hemodialysis, 23% died, 11% abandoned
      treatment, 8% continued on chronic ambulatory peritoneal dialysis and 6% received
      a kidney allograft. We conclude that intermittent peritoneal dialysis is a good
      alternative treatment of chronic renal failure, even in diabetic patients.

PMID- 8525191
TI  - [Results of the surgical treatment of colorectal cancer: analysis of recurrence
      and survival in 400 patients].
AB  - We analyzed retrospectively the long term survival and recurrence of 400 patients
      with colorectal cancer operated in a period of 13 years. Kaplan Meier curves were
      used for survival analysis and Cox's regression for multivariate analysis. Ninety
      eight percent of 377 surviving patients were followed for a mean period of 34 +/-
      36 months (range 12-156). Global recurrence was 32% and higher for rectal than
      colon cancer. Sixty five percent of recurrences were distant. The main prognostic
      parameter for recurrence was peritumoral lymph node involvement. The initial
      tumoral stage was the main prognostic factor for survival. Five years survival
      probability was 94.4% in stage A, 81.3% in stage B, 63.8% in stage C1, 41.3% in
      stage C2 and 3.1% in stage D. Preoperative radiation therapy did not improve
      survival or recurrence. Postoperative radiation therapy prolonged the lapse
      between surgery and recurrence, without changing overall survival. The prolonged
      survival of some patients in stage D justifies palliative surgery in this stage.

PMID- 8525192
TI  - [Pattern of antimicrobial susceptibility of enterococci strains].
AB  - Enterococci resistance to antimicrobials has increased lately. We studied the
      susceptibility to 12 antimicrobials of 150 enterococci strains coming from
      hospitalized and outpatients, using the agar dilution method. Teicoplanin,
      followed by imipenem and amoxicilin-clavulanic acid had the lower minimal
      inhibitory concentrations. No strains of E faecalis was resistant to ampicillin,
      whereas 14% of E faecium had minimal inhibitory concentrations over 8
      micrograms/ml. The high minimal inhibitory concentrations of cefpirome (64
      micrograms/ml) renders this antimicrobial useless in the treatment of
      enterococcal infections. Betalactamase production and resistance to glucopeptides
      were not detected. Antimicrobial susceptibility of strains coming for
      hospitalized or outpatients were similar.

PMID- 8525193
TI  - [Annual frequency of Cryptosporidium parvum infections in children and adult
      outpatients, and adults infected by HIV].
AB  - We report the analysis of 4892 parasitological stool samples coming from
      outpatients and patients of a nutritional recuperation center of north Santiago.
      Cryptosporidium parvum was detected in 21 samples (0.4%). The protozoan was
      detected in 6 of 1203 samples from children of less than 2 years old, 3 of 1.727
      samples from children between 6 and 15 years, none of 776 samples from healthy
      adults and 2 of 13 samples from HIV infected patients. Nine of 97 children of
      less than 2 years old, hospitalized in the nutritional recuperation center, were
      infected with Cryptosporidium; this frequency was significantly higher than that
      of outpatients of the same age. Most infections were detected from May to August,
      a rainy and mildly cold period. It is concluded that Cryptosporidium infections
      are infrequent in healthy outpatients and that its prevalence increased in
      hospitalized children and HIV infected adults.

PMID- 8525194
TI  - [Regional transient osteoporosis and reflex sympathetic dystrophy. Are they
      different entities or clinical variants of the same disease?].
AB  - We report a 50 years old male that evolved with alternating episodes of
      osteoporosis with pain, edema and erythema of both feet. The patient presented
      clinical and radiological evidences of both transient regional osteoporosis and
      reflex sympathetic dystrophy. The clinical evolution was documented with magnetic
      resonance imaging. The hypothesis that both entities could be different
      expressions of same syndrome is discussed.

PMID- 8525195
TI  - [Arrhythmogenic right ventricular dysplasia. Options of treatment during a 12
      year follow-up of a patient].
AB  - The replacement of muscle by fibrous and adipose tissue leads to arrhythmogenic
      right ventricular dysplasia. We report the clinical features and therapeutic
      options of a 50 years old male with the disease followed during 12 years. The
      latter included pharmacological therapy, surgical pseudoaneurysmal resection and
      radiofrequency fulguration of a second arrhythmogenic focus that appeared 10
      after the surgical procedure. The patient remained asymptomatic after each
      therapy, until the disease progressed again. This follow up is one of the longest
      reported and documents the disease's clinical presentation, evolution and
      treatment.

PMID- 8525196
TI  - [Refractory epilepsy in adults and the new antiepileptic drugs: the role of
      gabapentin].
AB  - The features of refractory epilepsies and the role of functional surgery and new
      antiepileptic drugs is reviewed. Among the latter, gabapentin, a drug with
      peculiar pharmacokinetic properties, is highlighted as a therapeutic alternative
      in refractory epilepsies and eventually for epileptic patients without previous
      treatment. A new type of relationship between the pharmaceutical industry and
      physicians, that privileges clinical research, is discussed.

PMID- 8525197
TI  - [Nutritional status of school children in poverty conditions from urban and rural
      areas. Metropolitan region. Chile. 1986-1987].
AB  - The aim of this study was to compare the nutritional status of poor children from
      urban and rural areas and to quantify the impact of socioeconomic, sociocultural
      and family variables on nutritional status. Weight/age, height/age, weight/height
      and head circumference percentages were measured in a representative sample of
      4509 school children, 39% belonging to a low socioeconomic status and living in
      the Metropolitan region, chosen according to grade, type of school, sex and
      geographic area. Children coming from rural areas had significantly higher
      percentages of undernutrition than children from urban areas according to
      weight/age (47 vs 34%, and weight/height (7.7 vs 4.6%); likewise they had a
      higher proportion of height/age ratios below 90% (10.3 vs 5.2%). Head
      circumference was below 100% in 77 and 65% of rural and urban children. Brachial
      anthropometric variables were also lower in rural children. The number of
      siblings and family size were the independent variables with the greatest
      explanatory power for weight/age and height/age variations. Mother's instruction
      in urban areas and crowding, family alcoholism and mother's instruction in rural
      areas, were the independent variables with the greatest explanatory power for
      head circumference variation. It is concluded that the significant relationship
      found between socioeconomic, sociocultural and family variables ad nutritional
      status is relevant, considering that the sample was homogeneous in each
      geographic area.

PMID- 8525199
TI  - [The creation of the World Association of Medical Editors (WAME)].

PMID- 8525198
TI  - [Presumptive organ donations for transplants agreement of the Ethics Committee of
      the University of Chile Medical School].
AB  - The ethics committee of the Faculty of Medicine, University of Chile was
      consulted about the ethical aspects of presumptive organ donation for
      transplantation. After analyzing the problem, the committee concluded that every
      human being has the right to make use of his organs freely, voluntarily and
      according to his own discernment. The society has no right to make obligatory
      this donation, even after death. The foundations of this agreement were laid in a
      series of reasons. In fact, the corpse is not a juridical but a ethical asset and
      deserves respect for whom it was. It cannot be commercialized and is the only non
      religious object susceptible of profanation. It is also object of popular
      affective and religious manifestations. Beliefs and affects must be respected.
      Organ donation is an act of charity and cannot be compulsory. The organ donation
      consent must be explicit, voluntary and solemn.

PMID- 8525200
TI  - [Antigenic types of circulating rotavirus in children with acute diarrhea in
      Santiago de Chile].
AB  - Protective immunity against rotavirus infection is directed against antigenic
      epitopes on the outer capsid proteins VP7 and VP4. The aim of this study was to
      characterize the VP7 and VP4 antigenic types circulating in different hospital
      areas of Santiago, Chile, over different time periods. Between April 1993 and
      April 1994 a total of 1206 stool samples were obtained from children consulting
      for acute no bloody diarrhea in 5 hospitals representative of the 5 major health
      areas of Santiago. In addition, 256 rotavirus positive samples, obtained from
      children with acute diarrhea consulting in the north health area of Santiago
      between 1985-1987 were studied. All samples were processed for rotavirus by an
      ELISA and all rotavirus positive samples were VP7 typed (types G1-G4) by a
      monoclonal antibody based ELISA. 50 rotavirus positive samples were selected for
      VP4 typing by PCR (types P1-P4). A total of 782 rotavirus positive samples were
      obtained of which 618 (79%) were typable for one specific VP7 type. VP7 type G1
      represented 63% of the rotavirus positive samples and predominated in all areas
      evaluated throughout the entire period of observation. VP7 type G2 represented
      13% of rotavirus samples, following G1 in predominance. G2 types decreased
      progressively in all areas in both study periods. G4 types were detected mainly
      during 1985-1987, and G3 types have so far not been detected. Preliminary
      analysis of VP4 types suggests that P1 types are predominant and closely
      associated with VP7 G1 type. These results are relevant for the adoption of
      appropriate preventive strategies for rotavirus infection, specifically aimed to
      the development of effective vaccines.

PMID- 8525201
TI  - [Paternity study applying DNA polymorphism: evaluation of methods traditionally
      used in Chile].
AB  - Simultaneous detection of several VNTR loci using a single DNA probe is the basis
      of the technique called "DNA fingerprint" (DNAfp) of increasing application in
      parenthood identification. According to the data gathered by different
      laboratories worldwide, father exclusion can be made in a larger number of cases
      when compared with the customary tests based on erythrocyte antigens. The
      question could then be whether DNAfp will completely replace erythrocyte antigens
      tests. We report here our experience in applying DNAfp to 92 samples
      corresponding to 34 paternity cases and comparing these with the results obtained
      with the antigens of the systems ABO, Rh, MNSs, Duffy and Kidd. Most of the
      HaeIII/digested DNA samples produced 13 to 16 bands larger than 4.3 Kb (average
      14,0761 +/- 2,205). Average band sharing between pairs of unrelated individual
      was 1,9107 +/- 1,083. Two cases presenting an a posteriori probability of being
      the father of 80.7% and 76.5% by erythrocyte antigens were clearly excluded by
      DNAfp. All exclusions made by antigens were confirmed by DNAfp. In the cases
      reported as father "rather probable" (28 cases) by DNAfp, these shared with the
      child 6,7407 +/- 1.7 bands on average. Because of time, cost and simplicity we
      favor a procedure starting with the antigens test and continuing with DNAfp only
      when an exclusion is not possible. Economy will increase as the number of
      exclusions increases.

PMID- 8525202
TI  - [Pre S1 antigen in different forms of hepatitis B virus infection].
AB  - Pre S1 antigen was measured using an ELISA technique in patients with different
      forms of hepatitis B virus infection. It was detected in 10 of 19 patients with
      acute hepatitis B (53%), 12 of 15 chronic hepatitis B virus carriers (80%), 9 of
      11 patients with chronic hepatitis B (82%) and 3 of 4 patients with hepatoma and
      positive markers of hepatitis B virus infection. Pre S1 remained positive beyond
      150 days in two patients with acute hepatitis that evolved to chronicity. Among
      subjects with chronic hepatitis B that received interferon, pre S1 antigen
      negativized only in the patient that had a complete response. Pre S1 detection is
      an index of hepatitis B virus replication and its persistence determines
      chronicity. Its negativization after antiviral therapy should have a predictive
      value.

PMID- 8525203
TI  - [Cardiopulmonary exercise test in patients with chronic cardiac failure:
      comparison with normal subjects and reproducibility of measurements].
AB  - The aim of this work was to measure oxygen consumption and carbon dioxide
      production during exercise in 21 subjects with cardiac failure and 13 normal
      subjects. During the resting period, subjects with cardiac failure had higher
      ventilatory frequency and respiratory quotient than normals. During maximal
      exercise, the former achieved higher ventilatory frequency and oxygen ventilatory
      equivalent than normals. In subjects with cardiac failure and normals, anaerobic
      thresholds were 14.4 +/- 0.9 and 28.8 +/- 2.2 ml/kg/min respectively and peak
      oxygen consumptions 17.1 +/- 1 and 34.4 +/- 1.7 ml/kg/min respectively. There
      were less than 10% differences in parameters when tests were repeated in 10
      subjects with cardiac failure. It is concluded that gas exchange testing may be a
      reliable and objective assessment method in patients with cardiac failure.

PMID- 8525204
TI  - [Gallbladder cancer. Case-control study].
AB  - Gallbladder cancer is the principal oncological cause of death in chilean women
      and cholelithiasis is a well recognized risk factor. Aiming to unravel other risk
      factors for gallbladder cancer, we compared 50 patients subjected to
      cholecystectomy in whom a gallbladder cancer was found with 50 age and sex
      matched operated controls without cancer. Subjects were clinically assessed and
      interrogated about demographic, obstetrical features and feeding features.
      Multiples and early pregnancies were factors significantly associated to the
      development of gallbladder cancer. Twenty subjects (44%) with cancer knew that
      they had cholelithiasis and 41 patients in each group were symptomatic. It is
      concluded that pregnancy may be a risk factor for gallbladder cancer probably due
      to the lithogenic effect of its hormonal changes. Also, early cholecystectomy in
      symptomatic individuals may be an effective preventive measure.

PMID- 8525205
TI  - [Head circumference in Chilean school children 5 to 18 years of age and
      socioeconomic status].
AB  - The objectives of this study were to determine the head circumference (HC) values
      of a representative sample of 4,346 school children aged 5 to 18 years from
      Chile's Metropolitan Region, to carry out a comparative study with international
      reference data of Tanner, Nellhaus and Roche et al and to compare the HC values
      by socioeconomic status (SES). The sample included school children of both sexes,
      from public, private subsidized and private non-subsidized schools and from urban
      and rural areas. HC was measured according to Jelliffe norms and SES through
      Graffar's Modified Method. Results showed a high correlation between HC values of
      school-age children from Chile's Metropolitan Region and Tanner, Nellhaus and
      Roche et al Tables, with similar growth curves; from this manner, HC values of
      school-age children from Chile's Metropolitan Region not differ significantly
      from international reference data. HC values were, in general, significantly
      higher in males than females in all age groups, in students from high SES to
      compare with other socioeconomic strata and in older school children. This fact
      was tested too in 1992, in a representative sample of 605 poor school children
      beneficiaries from the School Feeding Program in Penalolen and Pirque Counties
      from Chile's Metropolitan Region with similar results. It can be concluded that
      HC values of school-age children from Chile's Metropolitan Region were higher in
      males than females, in high SES compared with medium and low SES and in older
      students and does not differ significantly from international reference data.

PMID- 8525206
TI  - [Correlation between four-hour creatinine clearance and 51Cr-EDTA test].
AB  - BACKGROUND: Creatinine clearance as a measure of glomerular filtration rate has
      several sources of error such as tubular creatinine secretion or faulty urine
      collections. On the other hand 51Cr-EDTA test is reliable and accurate, except in
      patients with edema, in whom the radioisotope equilibrium is retarded after
      injection. AIM: To validate a 4-hours creatinine clearance correlating it with
      51Cr-EDTA test. METHODS: In 59 non insulin dependent diabetic patients without
      diabetic nephropathy, glomerular filtration rate was measured using one 50
      microCi injection of 51Cr-EDTA and collecting blood samples for radioactivity
      measurement at 10, 30, 120 and 240 min. Simultaneously, creatinine clearance was
      measured using a 4 hours urine collection. RESULTS: The general correlation
      coefficient between both methods was 0.85 (p < 0.001). For glomerular filtration
      rates below 95 ml/min, the correlation coefficient was 0.8 (p < 0.001), for
      values between 95 and 127 ml/min, the correlation was 0.51 (p < 0.001) and for
      values over 127 ml/min the correlation was 0.8 (p < 0.001). The regression
      equation obtained was y = 1,2x + 13 where y was the glomerular filtration rate
      measured with 51Cr-EDTA and x the same value measured with creatinine clearance.
      CONCLUSIONS: The four hours creatinine clearance is a reliable method to estimate
      glomerular filtration rate.

PMID- 8525207
TI  - [Allogenic bone marrow transplantation in the treatment of malignant hematologic
      disease].
AB  - We have treated 28 patients (pts) with malignant hematological diseases with
      allogeneic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic
      (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2
      severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced
      Non Hodgkin's lymphoma. All but three received the graft from HLA identical
      sibling donors. We used conditioning with total body irradiation and chemotherapy
      (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in
      11. 24 pts had full hematological recovery 18 to 25 days post BMT. 15 pts died
      after BMT as a consequence of toxicity or early infection (4), graft failure (2),
      graft versus host disease (4) or relapse (5). Actuarial event free survival for
      the group with favorable prognosis (SAA, ALL and ANLL in first or second
      remission and CML in chronic phase) is 57% at 36 months. Allogeneic BMT is an
      effective and feasible therapeutic procedure for selected patients with
      hematological malignancies.

PMID- 8525208
TI  - [Systemic toxocariasis in the adult patient].
AB  - We report a retrospective review of eight patients (one male), aged 19 to 31
      years old, with systemic toxocariasis (visceral larva migrans), seen at the
      Salvador Hospital of Santiago. Four cases had heart involvement, three had lung
      involvement and in two, several organs were affected. Seven cases had
      leukocytosis (range 14, 5 to 160 x 10(9)/l) and all had eosinophilia (35 to 90%).
      Serum ELISA titers for Toxocara sp were positive in all cases, ranging from 64 to
      1000. Six patients were treated with thiabendazole and one with albendazole.
      Steroids or hydroxiurea were administered to patients with heart failure or
      hyperleukocytosis. Subjects with lung involvement recovered quickly but those
      with cardiac compromise had a partial recovery with frequent decompensations of
      their cardiac failure and one death. Eosinophilia lasted up to 20 years, in spite
      of specific treatment. We emphasize the importance of infection prevention,
      accuracy of diagnosis and the severity of cardiac damage in the adult patient.

PMID- 8525209
TI  - [Intestinal obstruction caused by peritoneal carcinomatosis due to signet ring
      cell carcinoma of the breast].
AB  - The signet ring variant of lobular mammary carcinoma is aggressive and metastasis
      to serosal surfaces. We report a 46 years old woman presenting with an intestinal
      obstruction due to a peritoneal carcinomatosis secondary to a signet ring cell
      carcinoma of the breast. After surgery, the patient received chemotherapy (5
      fluorouracil, adriamycin, cyclophosphamide and tamoxifen). A satisfactory
      response, with regression of peritoneal carcinomatosis and a good quality of
      life, was achieved. The patient is alive after 2 years of diagnosis.

PMID- 8525210
TI  - [Sympathetic denervation of an extremity as a presentation form of apical lung
      cancer].
AB  - We report a 56 years old male patient presenting with a sympathetic denervation
      of the right upper limb due to an apical lung cancer. Vasomotor paralysis of the
      limb was objectively documented with a contact termography. The clinical
      presentation of this patient was unusual, considering that the alteration
      occurred without sensory or motor changes of the limb or autonomic disturbances
      of the face. The absence of clinical and neurophysiological involvement of large
      and small caliber fibres of the brachial plexus and the lack of autonomic
      dysfunction of the face was explained by a predominant tumoral infiltration of T2
      and T4 ventral roots, which supply autonomic innervation to the upper limbs.

PMID- 8525211
TI  - [Opioid receptors in the era of molecular biology: they account for more than
      6,000 years of empirical pharmacology].
AB  - The medicinal use of opium and of morphine in different cultures and ancient
      civilizations is described. Research within the past 40 years have demonstrated
      the existence of brain opiate receptors. Morphine and related opioid analgetic
      interact at these sites in the nervous system to produce the characteristic
      pharmacological effects of these drugs. The opiate receptors have structural
      homologies with a variety of other cell membrane receptors; they activate second
      messenger-based chemical transduction systems in the cell membrane and are
      endowed with several regulation mechanisms. These opiate receptors are presumably
      activated under specific physiological conditions by endogenous ligands
      (opiopeptins). It is currently thought that morphine mimicks the opiopeptins by
      interacting with these receptors either at different molecular subsites or with a
      different mode of action.

PMID- 8525212
TI  - [Anorexigenic drugs in the treatment of obesity].
AB  - Obesity is highly prevalent and has several adverse effects on health. Its
      treatment is thus warranted and must aim to modify dietary and physical activity
      habits. The opinion of this association is that anorexigenic drugs with
      cathecolaminergic action (diethylpropion, phentermine, mazindol and
      phenylpropanolamine) or serotoninergic action (fenfluoramine and fluoxetine) may
      be used in moderate or severe obesity (BMI > 30 kg/m2) after a complete clinical
      assessment and in the context of an integral medical treatment. This association
      recommends a close surveillance of the use of these drugs, specially when
      formulated as non-proprietary prescriptions.

PMID- 8525213
TI  - [The internist, today].
AB  - The crisis of Internal Medicine is universal, and its fragmentation in an
      increasing number of sub-specialties is still taking place, with the undesirable
      results of dehumanization, excessive technification and increasing costs. Recent
      data indicate the growing and worrisome shortage of general internists in our
      country. The Medical disadvantages of the predominant care by sub-specialists are
      analized. The main features of the modern general internist are described.
      Changes in medical education and health policies to increase their number and
      professional quality are suggested.

PMID- 8525214
TI  - [Does Piero Di Cosimo's painting "The death of Procris" represent a
      tracheotomy?].

PMID- 8525215
TI  - [Genes of negroid origin in a urban population of Santiago].

PMID- 8525216
TI  - [Retained prescription for benzodiazepines].

PMID- 8525217
TI  - [Smoking in Santiago, 1993-94].
AB  - The aim of this work was to study smoking habits, alcohol and drug use and living
      standards in a random sample of 1000 dwellings and 4700 people of Santiago
      through periodic surveys during 1993 and 1994. Forty nine percent of dwellings
      had at least one inhabitant that was a daily smoker and 73% had at least one
      occasional smoker. Thirty seven percent of subjects older than 15 years were
      smokers (40% of men and 35% of women), 27% were presumably addicted to tobacco
      and 16% former smokers. Alcohol abuse had a prevalence of 2.3%. The highest
      prevalence of smoking was noticed in low socioeconomical strata. Smoking was not
      related to educational level or emotional disturbances. Frequency of alcohol
      abuse or marihuana use was 8.8 times higher in former smokers and 25 times higher
      in actual smokers, compared to people that never smoked. Comparing these results
      with previous population surveys, the prevalence of smoking increased in the
      period 1971-1986 from 47 to 51% in men and from 26 to 43% in women. On the other
      hand, during the period 1986-1994 the prevalence decreased from 51 to 40% in men
      and from 43 to 35% in women.

PMID- 8525218
TI  - [Current situation of human hydatidosis in Chile. 2 proposals for correcting its
      undernotification].
AB  - Hydatidosis continues to be a prevalent disease in Chile. Since 1985 and until
      1990, the number of notified cases decreased abruptly, probably due to sub
      notification. Lethality, not calculated officially, increased since 1985 in a
      roughly similar proportion to the decrease in communicated incidence. This fact,
      along with an increase in hospital discharges due to the disease in the country,
      confirms the hypothesis that sub-notification is true. Two estimation systems for
      the magnitude of sub-notification are proposed, one based in the expected
      lethality and the other in the corrected hospital discharges, taking into account
      the phenomenon of re-admission. Both systems, although differing, disclose much
      higher incidence of hydatidosis than the communicated figure. A critical analysis
      of both systems is done.

PMID- 8525219
TI  - [Dr Ricardo Katz Ugarte].

PMID- 8525220
TI  - [Major histocompatibility system as a risk factor for alcoholic liver disease].
AB  - Several associations between alleles of the major histocompatibility system and
      alcoholic liver disease have been described. However, these are weak and change
      from one population to another. The aim of this work was to search for a possible
      genetic risk factor for alcoholic liver disease among Chilean alcoholics. We
      studied blood groups, serum proteins and HLA antigens in 39 alcoholic cirrhotics,
      104 asymptomatic alcoholics and 44 non alcoholic controls. Asymptomatic
      alcoholics were also subjected to a percutaneous liver biopsy that showed
      moderate to severe histological liver damage in 46 subjects (44%). No differences
      in the studied genetic markers, were found among the four groups. It is concluded
      that this study does not confirm previously reported associations between genetic
      markers and alcoholic liver disease.

PMID- 8525221
TI  - [Prevalence of postpartum depression and associated factors in Santiago, Chile].
AB  - The aim of this study was to estimate the prevalence and factors associated to
      postpartum depression (PPD) in a sample of women attending clinics representative
      of different socioeconomic levels in Santiago. A total of 542 mothers selected
      from five health centres filled in the Edinburgh Postnatal Depression Scale which
      was used as the diagnostic criteria, a score of 10 and above being considered
      diagnostic of depression. Based in our findings, the prevalence of PPD would be
      36.7% after adjusting for socioeconomic distribution in Santiago. An inverse
      relationship was found between socioeconomic status and prevalence of PPD.
      Mothers with lower incomes had a three-fold increase in prevalence of PPD in
      comparison to mothers with higher incomes. Single mothers (unmarried, separated
      and widows) were twice more likely to be cases of PPD.

PMID- 8525222
TI  - [Evaluation of a computer-based independent study program applied to fourth year
      medical students].
AB  - The aim of this work was to assess an independent study program on hypertension
      using a computer multimedia program developed by the authors. Twenty-four
      randomly chosen students participated in the program and 76 students that
      continued to attend to classical lectures were used as controls. At the end of
      the program, a cognitive test with 40 multiple choice questions and an opinion
      questionnaire were applied. The experimental group had higher grades in the test
      than controls (71.4 and 64.6% respectively p < 0.001) and a highly favourable
      opinion of the program. It is concluded that computer based teaching programs are
      a useful and feasible alternative to lectures.

PMID- 8525223
TI  - [Development and evaluation of a measure scale of risk of mother-newborn infant
      relations].
AB  - The purpose of this work was to construct and assess a scale aimed to detect
      risky relationships between mothers and newborns that could predict future child
      abuse and neglect. The instrument was applied in two opportunities, by a trained
      midwife and by an expert in mental health, to a sample of 106 mother-newborn
      dyads. When both assessments were compared, the concordance to assess
      relationship risk was 99.3%. The reliability of the scale, measured with the
      Crombach, an internal consistence index, was 0.88. Those items with a low
      discriminative capacity were eliminated. The massive use of the resultant scale,
      that is easy to apply and highly reliable, could help to prevent child abuse and
      neglect.

PMID- 8525224
TI  - [Amiodarone absorption and elimination after oral and intravenous administration
      in healthy individuals].
AB  - We studied amiodarone absorption and disposal in eight male healthy subjects aged
      21 +/- 1 years old and weighting 69.8 +/- 7.1 kg. An intravenous dose of 5 mg/kg
      and an oral dose of 600 mg of amiodarone were administered. Amiodarone
      concentrations were measured by HPLC and calculations were performed using a
      compartment model independent pharmacokinetic analysis program. After oral
      administration a Cmax of 1.17 +/- 0.3 mg/ml was achieved at 3.25 +/- 0.46 h
      (tmax). Absolute bioavailability ranged from 50.4 to 87.8% (68.6 +/- 12.6%).
      Compared to previous reports, the variability of this parameter is similar and
      the mean value is one of the highest informed. After intravenous administration,
      Amiodarone had a half life of 7.53 +/- 0.96 h, a total body clearance of 4.25 +/-
      0.73 ml/kg/min and a distribution volume of 2.99 +/- 0.71 l/kg. Except the later
      figure, which is in the inferior range, all other parameters are within
      previously reported values. It is concluded that amiodarone absorption and
      disposal values found in Chilean subjects are similar to those reported abroad.

PMID- 8525225
TI  - [Size and echogenicity of the pancreas in Chilean adults: echotomography study in
      261 patients].
AB  - The aim of this work was to perform ultrasonographic measurements of normal
      pancreas in the Chilean population. Among 5000 subjects referred for an
      ultrasound abdominal examination, those without history of alcoholism,
      pancreatitis or liver disease were selected for the study. 261 individuals (157
      female) aged 20 to 79 years were studied. The size of the head of the pancreas
      ranged from 6 to 28 mm (17.7 +/- 4.2 mm), the body size ranged from 4 to 23 mm
      (10.1 +/- 3.8 mm) and the tail size from 5 to 28 mm (16.4 +/- 4.2 mm). These
      figures are lower than those reported in Europe and North America. No size
      differences were observed according to sex or body frame. Progressive declines in
      size with age, were observed in all pancreatic segments. No hypoecogenic pancreas
      were observed. A new technique to improve pancreatic ultrasonographic vision is
      proposed.

PMID- 8525226
TI  - [Primary coronary angioplasty as a choice treatment in the 1st 6 hours following
      acute myocardial infarction].
AB  - Primary coronary angioplasty as treatment of acute myocardial infarction
      preserves more myocardium and has a lower mortality than thrombolysis. Aiming to
      assess the feasibility of its use in Chile, we studied 64 patients aged 59 +/- 2
      years old, 27 with an anterior wall and 37 with an infero-lateral wall acute
      myocardial infarction of 118 +/- 62 min of evolution. Coronary angiography,
      performed 98 +/- 47 min after diagnosis, showed non significant disease in one,
      one vessel disease in 26 (40%), two vessel disease in 17 (27%) and three vessel
      disease in 20 (31%) patients. Responsible arteries for infarction were the
      anterior descending in 26 (40%), circumflex in 9 (14%), right in 27 (42%), a
      saphenous bridge in one and left main disease in one patient. In one patient with
      an obstruction over 50% and in two patients with left main disease, angioplasty
      was not attempted. The procedure was successful (defined as a residual lesion of
      less than 50%) in 56 of 61 patients (92%) and failed in four. One patient was re
      perfused with intracoronary streptokinase. The delay in reperfusion was lower
      during working than non-working hours (89 +/- 48 vs 113 +/- 39 min). Four
      patients (6%) died during hospitalization, two had a reinfarction, two had a new
      vessel occlusion and three had a spontaneous ischemia. Eleven patients were
      operated during hospitalization and in two this was an emergency procedure. After
      1993, mortality was lower (one of 55 patients) than before (three of nine). It is
      concluded that early coronary angioplasty in acute myocardial infarction is
      feasible in Chile, with a high degree of success.

PMID- 8525227
TI  - [Anticoagulation in hemodialysis with a single dose of low molecular weight
      heparin].
AB  - The aim of this work was to compare the benefits and problems of low molecular
      weight heparin use in chronic hemodialysis, compared to conventional heparin. We
      studied 35 patients that received low molecular weight heparin (Enoxaparine,
      molecular weight 4000) during 115 consecutive hemodialysis procedures and
      conventional heparin during the subsequent 35 procedures. We assess the heparin
      dose, partial thromboplastin time before dialysis and at 3 and 120 min during the
      procedure, arterio-venous fistula compression time, clot formation in the circuit
      and residual volume of filters. Median total dose of conventional heparin was
      6289 U (range 3000-10000) compared to 5555 U (range 2000-8000) of low molecular
      weight heparin. When the dose was calculated per kg of body weight, it was lower
      for low molecular weight heparin than for conventional heparin (87.8 U (range 33
      100) vs 100 U (range 50-176)). Partial thromboplastin time achieved was lower
      with low molecular weight heparin, compared with conventional heparin, at 3
      (64.26 vs 125.2 sec) and 120 min (39.1 vs 84.45 sec). Clot formation,
      arteriovenous fistula compression time and residual volume of filters were
      similar for both types of heparin. It is concluded that a single dose of low
      molecular weight heparin simplifies anticoagulation during hemodialysis, modifies
      less the partial thromboplastin time and does not alter filter re-utilization.

PMID- 8525228
TI  - [Pharmacokinetics and clearance of ciprofloxacin and amikacin in continuous
      hemodialysis].
AB  - We studied the pharmacokinetic and clearance of a 200 mg ciprofloxacin and a 500
      mg amikacin intravenous dose during 5 continuous hemodialysis procedures in 5
      patients with acute oliguric renal failure. Hourly blood and ultrafiltrate drug
      concentrations were measured during 8 hours. Dialysate flux (Qd) was 16.6 ml/min
      during the first hours and 33.2 ml/min thereafter. For each Qd, total
      ciprofloxacin clearance was 1.13 +/- 0.99 and 2.8 +/- 1.71 ml/min (p < 0.001),
      diffusive clearance was 0.96 +/- 0.87 and 2.47 +/- 1.56 ml/min (p < 0.005) and
      convective clearance was 0.16 +/- 0.17 and 0.33 +/- 0.2 ml/min (p < 0.05).
      Likewise, total amikacin clearance was 3.47 +/- 1.31 and 4.18 +/- 0.53 ml/min (p
      < 0.001), diffusive clearance was 2.97 +/- 1.24 and 3.86 +/- 0.52 ml/min and
      convective clearance was 0.50 +/- 0.47 and 0.32 +/- 0.29 ml/min (p = NS). Protein
      binding was 84% for ciprofloxacin and 77% for amikacin. It is concluded that
      during continuous hemodialysis with cuprofan membrane, the main transport
      mechanism of ciprofloxacin and amikacin is diffusive. Very low amounts of
      ciprofloxacin are depurated by the dialyser. Likewise, the shortening of amikacin
      half life suggests the presence of other elimination pathway and the need to use
      supplementary doses every 24 hours.

PMID- 8525229
TI  - [Acute myocardial infarction: pharmacological reperfusion or angioplasty?].
AB  - For patients with acute myocardial infarction intravenous thrombolytic therapy
      has become the standard care in restoring patency of the infarct-related coronary
      artery. Nearly 200.000 patients have been involved in thrombolytic trials over
      the last decade. A significant decreases in short-term mortality has been shown
      for those patients who are eligible for treatment with thrombolytics. However, in
      approximately 20% of patients patency is not achieved, a high-grade residual
      coronary stenosis is left, reocclusion of the open vessel, an increased incidence
      of recurrent ischemia and serious bleeding complications can occur with this
      therapeutic modality, resulting in increased morbidity and mortality. There is an
      increasing interest in immediate angioplasty as an alternative to thrombolytic
      reperfusion during the first hours in patients with acute myocardial infarction
      hospitalized in those institutions that have the capability of performing
      angioplasty on an emergency basis. It has been shown that immediate angioplasty
      restored antegrade coronary perfusion in more than 90% and in 85 to 90% a
      complete blood flow (grade 3 by criteria of the TIMI trial) is achieved.
      Treatment of the residual coronary stenosis prevents recurrent isquemia, reduces
      the occurrence of nonfatal reinfarction, and fewer readmissions can be expected.
      Finally, angioplasty also provides a view of the coronary anatomy and identifies
      patients at high risk, some of whom need emergency bypass surgery, or patients
      with low risk who need a shorter hospital stay.

PMID- 8525230
TI  - [Adult cyclic neutropenia: acute ileitis as an initial clinical manifestation].
AB  - Cyclic neutropenia is a rare disease in which blood neutrophils periodically
      decrease and almost disappear, ensuing acute infections of variable severity. We
      report a 37 years old female presenting with severe abdominal pain, fever and
      neutropenia. During a surgical abdominal exploration, an acute ileitis was found.
      During a follow-up of 6.5 months, transient episodes of neutropenia (mean count
      of 0.33 x 10(9)/l), every 22-28 days, were detected. Coinciding with these
      episodes, band and segmented neutrophils disappeared from the bone marrow and its
      response to functional stimulation with prednisone was insufficient. No cyclical
      changes in lymphocytes, monocytes and packed red cell volume were observed. The
      episodes of severe transient neutropenia and infections persist after three years
      of follow up.

PMID- 8525231
TI  - [Myopathy caused by acid maltase deficiency in an adult].
AB  - We report a 46 years old male presenting with tetraparesis and severe respiratory
      involvement. He had moderately elevated serum creatine phosphokinase values and
      the electromyography showed myopathic alterations and irritative signs. In the
      muscle biopsy, a vacuolar myopathy with increased collagen deposits was found.
      Circulating lymphocytes presented abnormal PAS positive granules in their
      cytoplasm.

PMID- 8525232
TI  - [Update on microsporidiosis in humans].
AB  - The importance of microsporidium as an opportunistic agent in immunocompromised
      and AIDS patients is reviewed. Five strains of the agent have been described:
      Encephalitozoon, Enterocytozoon, Nosema, Pleistophora and Septata. The clinical
      presentation may be as 1) Generalized infections with multisystemic involvement,
      specially of the central nervous system; 2) Intestinal, that is the most
      important and frequent localization in man, and that may cause death in AIDS
      patients; 3) Ocular, that affects cornea, conjunctiva and may extend to paranasal
      sinuses; 4) Liver and biliary tract infection with granulomatous lesions, hepatic
      necrosis or sclerosing colangitis and 5) Muscular, affecting skeletal muscle. The
      diagnosis is difficult and is established finding spores in the affected tissues
      with light or electron microscopy. Lately, the diagnosis of intestinal
      microsporidiosis is made looking for faecal spores. The resistant wall of spores
      hampers treatment. However, good results are obtained with Albendazole in
      intestinal microsporidiosis.

PMID- 8525233
TI  - [Responsibility of universities in the scientific education of our
      professionals].
AB  - The universities have a leading role and responsibility in the scientific
      education of future professionals. Scientific research training should be
      considered essential in the teaching of professionals in areas such as biology,
      chemistry, physics, mathematics and in medicine. During the recent years, Chilean
      universities seem to have focused their undergraduate curricular activities into
      pragmatic aspects of professional practice and the relevance of involving
      undergraduate students in high-level scientific research receives little
      consideration. While resources provided by the government to scientific and
      technological research in Chile are slowly but gradually increasing, the
      participation of undergraduate students in specific research projects conducted
      by faculty members is minimal. The author proposes that this situation could be
      modified if the students are stimulated to participate in these research projects
      by receiving preferential scores when their elective activities are devoted to
      it.

PMID- 8525234
TI  - [Why bioethics today?].
AB  - Only recently medicine has emphasized the importance of major ethical principles
      (autonomy, beneficence, justice and non-malificence) and only recently they have
      come to play an important role in medical and public policy discussions. Until
      the 70's, medical dilemmas and disagreements were rarely discussed in terms of
      rights and duties. However, at this point in history, crucial new ideas were
      introduced, including the notion of Medical Bioethics. What seems important at
      this stage is to show if Bioethics has made a significant difference in the field
      of medicine. This article intends to give a picture of how ethical, historical
      and medical factors have influenced the beginning of Bioethics, in an attempt to
      determine how much it has been able to fulfill a genuine need.

PMID- 8525235
TI  - [Validation of a screening instrument for studying the prevalence of
      cerebrovascular diseases in the Chilean population].
AB  - We assessed a screening instrument, adapted from a model suggested by WHO, aimed
      to perform population studies on the prevalence of cerebrovascular disease in
      Chile. Sixty-two subjects, 31 with cerebrovascular diseases and 31 without, were
      asked about symptoms and requested to do simple movements by trained
      interviewers. The results of the instrument were compared with a neurological
      examination performed by two specialists. Global sensitivity and specificity of
      the instrument, using WHO evaluation criteria, were 100 and 38.7% respectively.
      When three or more symptoms and one positive sign were considered as cutoff
      points, global specificity increased to 61% and sensitivity decreased to 93%. It
      is concluded that the present instrument is highly sensitive but lacks
      specificity.

PMID- 8525236
TI  - [Accidents in children and adolescents. Introduction].

PMID- 8525237
TI  - [Prospective study of accidents in children in the Vevey metropolitan area].

PMID- 8525238
TI  - [Accident prevention in 0-to-5-year-old children in Vaud: implications of a
      population study for medical practice].

PMID- 8525239
TI  - [Evaluation of medical transport of injured children in the Vaud canton].

PMID- 8525240
TI  - [Accidents in children and adolescents: from analysis to prevention].

PMID- 8525241
TI  - [Adolescence: child psychiatry aspects].

PMID- 8525242
TI  - [Health promotion in young people and the campaign against cardiovascular risk
      factors].

PMID- 8525243
TI  - [How should patients with coronary disease and a very poor left ventricular
      systolic function be treated?].

PMID- 8525244
TI  - [Cardiac transplantation: current status of activity in Lausanne from 1987 to
      1994].

PMID- 8525245
TI  - [Contribution of transcranial Doppler ultrasonography in neurology].

PMID- 8525246
TI  - [Minor cranio-cervical injuries, cerebral malformations and chronic headaches].
AB  - We have presented two cases of chronic disabling exertional headaches following a
      minor head trauma. MRI studies of the cranio-cervical junction showed Chiari Type
      I malformation, without bony occipito-cervical dysplasia. Headaches after a mild
      trauma are a common finding. The exertional character of the headache can lead
      the clinician to his diagnosis in cases involving long-term complaints.

PMID- 8525247
TI  - [Alcohol and mortality].

PMID- 8525248
TI  - [Surgical treatment of epicondylitis].

PMID- 8525249
TI  - [Surgical treatment of epitrochleitis].

PMID- 8525250
TI  - [Plea for a better utilization of human resources in anesthesiology, and the
      creation of a replacement center for the use of French-speaking anesthetists].

PMID- 8525251
TI  - [Violence, a public health and social problem].

PMID- 8525252
TI  - [Ulcerative colitis and pericarditis. The role of mesalazine hypersensitivity].

PMID- 8525253
TI  - [Nutritional support, free radicals, and antioxidants].
AB  - Antioxidants and free radical scavengers are molecules endowed with the ability
      of neutralizing reactive oxygen species that may accumulate in the organism
      during various pathologic processes. In circumstances of peroxidation of lipids
      and damage to enzymatic chains, cell membranes and other structures may be
      followed by functional losses and even cell death. Many antioxidants are normal
      constituents of the diet in the form of vitamins, trace elements and amino acids,
      and other useful properties cannot be easily distinguished from their free
      radical scavenging abilities. Much controversy surrounds also the indications of
      these substances, both for prophylactic and therapeutic purposes. The first large
      scale population studies have only recently been arranged, and additional
      investigations are required in many promising areas, including cancer patients
      undergoing chemo and radiotherapy.

PMID- 8525254
TI  - Hypovolemic hemorrhagic shock (an experimental study).
AB  - With the objective of studying the natural defense mechanisms against traumatic
      hemorrhages, 20 mice were studies. Some of the large vessels were examined
      histologically after fixing with formaldehyde, in cases of bleeding, bleeding +
      hemodilution and controls. In the hemo-diluted group, important alterations in
      the distribution of the components of the blood stream were confirmed and in one
      case, there was extravasation of liquid poor in cellular elements. The results
      show that hemodilution is an unfavorable condition for the natural defense
      mechanisms against hemorrhage. The repercussion of these experimental results on
      clinical cases of traumatic hemorrhage is speculated.

PMID- 8525255
TI  - The tegument resulting from the healing of burns.
AB  - First the authors conceptualized healed burns, the tegument resulting from the
      healing of burns (TRH), and the 4 main species of teguments: 1--Regenerated skin;
      2--Restored skin; 3--Grafts and 4--Scars. One hundred patients at the Unit Burn
      from the Division of Plastic Surgery, Faculty of Medicine, University of Sao
      Paulo, Brazil, were then studied prospectively, and the respective teguments
      which resulted from the healing of the burns were analyzed in their qualitative
      and quantitative aspects. From the qualitative point of view, TRHs were
      classified into 7 types. The extensions of the species which comprised each type
      were calculated as a % of the TRH. From this analysis it was seen that restored
      skin was present in all patients and that pos-burn restored skin was the most
      frequent and most extensive species. It also became evident that restored skin
      has not been considered as such, since it has been incorrectly referred to as
      scar. From this qualitative and quantitative analysis a Quality Index was drawn
      up to objectively evaluate healed burns and, indirectly the caliber of the
      treatment carried out. It also become clear how heterogeneous are the teguments
      that make up healed burns and the importance of this fact for treating patients.

PMID- 8525256
TI  - [Prognostic value of the sites of pancreatic necrosis determined by computed
      tomography of the abdomen].
AB  - Correlations between tomographic findings and the outcome of the disease was made
      in 49 patients with necrotizing pancreatitis submitted to surgical treatment.
      Mortality rate was 20.40% resulting mostly from sepsis and multiple organ
      failures. There was no correlation between APACHE II index and number of necrotic
      areas diagnosed by abdominal computed tomography although they were closely
      related with mortality. These findings suggest that different necrotic areas have
      different prognostic values. The root of the superior mesenteric artery and
      retropancreatic area were related to worst prognosis with 100% mortality rate.
      Incomplete necrotic tissue removal is the possible explanation for the high
      mortality rate.

PMID- 8525257
TI  - [Colonoscopy: diagnostic and treatment methods].
AB  - The author presents the historical and technical development of the colonoscopy
      showing the advantages provided by the employment of the method, specially with
      the use of new equipment. He discusses different pre-colonoscopy bowel cleansing
      methods, and particularly the use of mannitol 10%.

PMID- 8525258
TI  - [Severe combined immunodeficiency: description of a clinical case].
AB  - A Severe Combined Immunodeficiency (SCID) is a rare disease, with recessive
      autosomic or X linked inheritance. The clinical phenotype is related to the
      defect of specific antigen response. The authors describe a patient presenting
      recurrent infections, affected by SCID, with multiple hospitalizations.
      Immunologic evaluation was performed and adenosine deaminase deficiency was
      excluded. The patient was submitted to herniography and he died seven days after
      the surgery. The preparation for bone marrow transplantation was provided. The
      anatomo-pathological findings had showed immunologic system alterations. The
      early clinical diagnosis and the therapy are discussed.

PMID- 8525259
TI  - [Curriculum evaluation program of the University of Sao Paulo Medical School-
      results for 1993 and a 5-year analysis].
AB  - The following report contains the results of the "Curricular Evaluation Program"
      of University of Sao Paulo Medical School pertaining to the year of 1993 and to
      the five-year period between 1989 and 1993. This evaluation of all undergraduate
      courses was made by students, responding to questionnaires supplied at the end of
      each program. In 1993, 60.6% of programs were considered as very good programs.
      In relation to 1989-1993 period, are presented the results of a disciplines group
      of the 4th year and a internship stages of the 5th year.

PMID- 8525260
TI  - [The medical school and surgery in Sao Paulo].

PMID- 8525261
TI  - Persistence of specific antibody response in different experimental infections of
      mice with Toxocara canis larvae.
AB  - Anti-Toxocara antibody production and persistence were studied in experimental
      infections of BALB/c mice, according to three different schedules: Group I (GI)
      25 mice infected with 200 T. canis eggs in a single dose; Group II (GII) 25 mice
      infected with 150 T. canis eggs given in three occasions, 50 in the 1st, 50 in
      the 5th and 50 in the 8th days; Group III (GIII)-25 mice also infected with 150
      T. canis eggs, in three 50 eggs portions given in the 1st, 14th and 28th days. A
      15 mice control group (GIV) was maintained without infection. In the 30th, 50th,
      60th, 75th, 105th and 180th post-infection days three mice of the GI, GII and
      GIII groups and two mice of the control group had been sacrificed and
      exsanguinated for sera obtention. In the 360th day the remainder mice of the four
      groups were, in the same way, killed and processed. The obtained sera were
      searched for the presence of anti-Toxocara antibodies by an ELISA technique,
      using T. canis larvae excretion-secretion antigen. In the GI and GII, but not in
      the GIII, anti-Toxocara antibodies had been found, at least, up to the 180th post
      infection day. The GIII only showed anti-Toxocara antibodies, at significant
      level, in the 30th post-infection day.

PMID- 8525262
TI  - Intestinal parasites in school food handlers in the city of Uberlandia, Minas
      Gerais, Brazil.
AB  - In order to verify the presence of intestinal parasites in food handlers, stool
      samples were collected from 104 cooks and their helpers that were working in food
      preparation in 20 public elementary schools, in various areas of the city of
      Uberlandia, Minas Gerais, Brazil. The samples were collected during the months of
      November and December, 1988, in plastic flasks containing a 10% formaldehyde
      solution and processed by the Hoffmann, Pons & Janer method. The sediment was
      examined using triplicate slides. All individuals were females aged between 24 to
      69 years. Intestinal parasites were found in 85.0% of the studied schools and
      47.1% of the studied food handlers (cooks and helpers) were found to be positive.
      Among the 49 infected food handlers, 32 (65.3%) carried a single parasite and 17
      (34.7%) carried two parasites. The following intestinal parasites were found:
      Giardia lamblia (21.1%), Entamoeba coli (21.1%), hookworms (9.6%), Ascaris
      lumbricoides (5.8%), Entamoeba histolytica (2.9%), Hymenolepis nana (1.9%),
      Strongyloides stercoralis (1.0%). These data emphasize the need for a rigid semi
      annual control in all school food handlers, including diagnosis, specific
      treatment and orientation about the mechanisms of transmission of the intestinal
      parasites.

PMID- 8525263
TI  - Influence of bacteria upon cytopathic effect and erythrophagocytosis of different
      axenic strains of Entamoeba histolytica.
AB  - At this moment, the duality of species suggested for E. histolytica is being
      considered for discussion. In order to contribute to settling this question, we
      investigated the possibility of conversion of avirulent ameba to virulent ones,
      as well as, the possibility of increasing virulence of virulent strains, by means
      of association with bacteria. Five strains of E. histolytica were employed, two
      of them regarded as avirulent and three virulent ones. Amebas were associated
      with the bacteria Escherichia coli 055 and 0115, previously demonstrated as
      capable to modify the pathogenic behavior of E. histolytica. Changes in virulence
      of amebas were assessed by cytopathic effect upon cultured mammal cells and
      erythrophagocytosis. The virulence of pathogenic strains was significantly
      increased after bacteria association in opposition to what was observed for
      nonpathogenic ones, which were not influenced by bacteria association.

PMID- 8525264
TI  - Development of Schistosoma mansoni in Biomphalaria tenagophila, Biomphalaria
      straminea and Biomphalaria glabrata.
AB  - A comparative study of the development of Schistosoma mansoni during the intra
      molluscan phase was made by means of histological sections of Biomphalaria
      tenagophila, B. straminea and B. glabrata from Brazil. Two hundred snails of each
      species were individually exposed to 50 miracidia of the S. mansoni, AL line. No
      larvae were observed in the snails fixed 72 h after exposure. In specimens
      shedding cercariae, 31 days after exposure tissue reactions encapsulating the
      larvae were seen in B. tenagophila and B. straminea, in the head-foot, mantle
      collar and renal ducts. No tissue reactions occurred in the digestive glands of
      these two species. In B. glabrata the presence of numerous sporocysts and
      cercariae without tissue reactions was observed in the digestive gland, and other
      organs. The levels of infection of the snails and the average numbers of
      cercariae shed per day were 32.6% and 79 +/- 90 respectively for B. tenagophila,
      11.3% and 112 +/- 100 for B. straminea and 75.3% and 432 +/- 436 for B. glabrata.
      The lower levels of infection and average numbers of cercariae shed by B.
      tenagophila and B. straminea are thus related to their more potent internal
      defense systems.

PMID- 8525265
TI  - Seroepidemiological and clinical study of Chagas' disease in Nicaragua.
AB  - With the aim of determining the prevalence, immunological profile, and knowing
      the electrocardiographic alterations, a clinical and seroepidemiological study of
      Chagas' disease was performed in three rural settlements located at the North,
      East and West of Nicaragua. Anti T. cruzi antibodies were searched by indirect
      immunofluorescence (IFI) and hemagglutination (IHA) in a total of 803 subjects.
      Seropositives and the same number of seronegatives, matched by age and sex, were
      included in a case-control design for the electrocardiographic assessment.
      Antibody prevalence was 13.1, 4.3 and 3.2% in the respective settlements. In the
      first two the immunological profile corresponds to that of an endemic zone of
      long standing, were transmission has decreased, and in the third the pattern is
      of a zone under control. Electrocardiographic changes compatible with Chagas'
      disease were found in seropositive individuals, but difference with control group
      was not statistically significant. It is concluded that the disease is endemic in
      the three settlements and the clinical aspect requires further evaluation,
      including additional cardiologic techniques.

PMID- 8525266
TI  - Haemolytic activity of Actinobacillus actinomycetemcomitans strains on different
      blood types.
AB  - Haemolytic activity of sixty nine Actinobacillus actinomycetemcomitans strains on
      different animal and human blood types was examined by using a trypticase soy
      agar supplemented with yeast extract (0.5%). Blood types used were: rabbit, sheep
      and human (A, Rh+; A, Rh-; B, Rh+; B, Rh-; O, Rh+; O, Rh-; AB, Rh+; AB, Rh-
      groups). Plates were inoculated and, incubated in microaerophilic conditions, at
      37 degrees C, for 48 h. The haemolytic activity of the tested strains was
      characterized as alpha-haemolysis. Only two isolates were not haemolytic on all
      blood types (2.9%), two strains were haemolytic only on human blood (one strain
      on AB, Rh+ group and another one on A, Rh+ and AB, Rh+ groups). No specificity
      between haemolysin produced by the tested strains and blood type was observed.

PMID- 8525267
TI  - Cyclophosphamide effect on paracoccidioidomycosis in the rat.
AB  - Paracoccidioidomycosis is an endemic fungal disease widely distributed throughout
      Latin America. The potent immunosuppressor cyclophosphamide (CY) has been used to
      modulate host immune response to Paracoccidioides brasiliensis in an experimental
      model. Inbred male Buffalo/Sim rats weighing 250-300 g were inoculated with 5 x
      10(6) P. brasiliensis cells of the yeast phase form by intracardiac route. One
      group of animals was treated with 20 mg/kg body weight at days +4, +5, +6, +7,
      +11 and +12 post-infection (pi.), while a control group was infected alone. No
      mortality was recorded in either group. Treated rats presented: a) a decrease in
      granuloma size, which contained less fungal cells; b) a lack of specific
      antibodies up to 35 days pi., and c) a significant increase in the footpad
      swelling test (DTH) against paracoccidioidin. Splenic cell transfer from CY
      treated P. brasiliensis-infected donors to recipients infected alone led to a
      significant increase in DTH response in the latter versus untreated infected
      controls. Likewise, in treated infected recipients transferred with untreated
      infected donor spleen cells, footpad swelling proved greater than in controls.
      Thus, it would seem that each successive suppressor T lymphocyte subset belonging
      to the respective cascade may be sensitive to repeated CY doses administered up
      to 12 days pi.. Alternatively, such CY schedule may induce the appearance of a T
      cell population capable of amplifying DTH response.

PMID- 8525268
TI  - Bancroftian filariasis in two urban areas of Recife, Brasil: the role of
      individual risk factors.
AB  - Bancroftian filariasis is spreading in towns of endemic areas in Recife,
      northeastern Brazil, where it is a major public health problem. This paper deals
      with the prevalence of microfilaraemia and filarial disease in two urban areas of
      Recife, studying their association with individual characteristics and variables
      related to the exposure to the vectors. The parasitologic survey was performed
      through a "door-to-door" census and microfilaraemia was examined by the thick
      drop technique using 45 microliters of peripheral blood collected between 20:00
      and 24:00 o'clock. 2,863 individuals aged between 5 and 65 years were interviewed
      and submitted to clinical examination. Males aged between 15 and 44 years old
      presented the greatest risk of being microfilaraemic. Microfilaraemia was also
      significantly associated with no use of bednet to sleep. The risk of being
      microfilaraemic was greater among those who had lived in the studied areas for
      more than 5 years. The overall disease prevalence was 6.3%. Males presented the
      greatest risk of developing acute disease. The risk of developing chronic
      manifestations was also greater among males and increased with age. We found no
      association between time of residence, bednet use, microfilaraemia and acute and
      chronic disease. We may conclude that in endemic areas there are subgroups of
      individuals who has a higher risk of being microfilariae carriers due to
      different behaviours in relation to vector contact.

PMID- 8525269
TI  - An exanthematic disease epidemic associated with coxsackievirus B3 infection in a
      day care center.
AB  - An epidemic of exanthematic illness in a day care center is described. Ten
      children aged 7 to 13 months were affected by the illness. The exanthem was
      characterized by nonconfluent macular or maculopapular lesions that appeared on
      the face, body and limbs. Fifty percent of the infected children had fever of up
      to 39 degrees C at the beginning of the disease. Coxsackievirus B3 (CB3) was
      isolated from the stool of one ill child. Paired serum samples were obtained from
      eight ill children and six of them presented seroconversion to CB3. Antibodies to
      CB3 were detected at titers higher than 16 in a single serum sample collected
      from the other two patients. Neutralizing antibodies to CB3 were detected in
      71.0% of the contact children.

PMID- 8525270
TI  - Long term follow-up and patterns of response of ALT in patients with chronic
      hepatitis NANB/C treated with recombinant interferon-alpha.
AB  - The response to interferon treatment in chronic hepatitis NANB/C has usually been
      classified as complete, partial or absent, according to the behavior of serum
      alanine aminotransferase (ALT). However, a more detailed observation of the
      enzymatic activity has shown that the patterns may be more complex. The aim of
      this study was to describe the long term follow-up and patterns of ALT response
      in patients with chronic hepatitis NANB/C treated with recombinant interferon
      alpha. A follow-up of 6 months or more after interferon-alpha was achieved in 44
      patients. We have classified the serum ALT responses into six patterns and the
      observed frequencies were as follows: I. Long term response = 9 (20.5%); II.
      Normalization followed by persistent relapse after IFN = 7 (15.9%); III.
      Normalization with transient relapse = 5 (11.9%); IV. Temporary normalization and
      relapse during IFN = 4 (9.1%); V. Partial response (more than 50% of ALT
      decrease) = 7 (15.9%); VI. No response = 12 (27.3%). In conclusion, ALT patterns
      vary widely during and after IFN treatment and can be classified in at least 6
      types.

PMID- 8525271
TI  - Leishmania braziliensis: isolation of carbohydrate-containing antigen and
      possibility of its use in the immunodiagnosis of American cutaneous
      leishmaniasis.
AB  - Leishmania braziliensis is a causative agent of American Cutaneous Leishmaniasis
      (ACL). The 034-JCG strain, isolated from a patient from the northern region of
      Parana State, Brazil, was cultivated in Blood Agar Base medium, lyophilized and
      submitted to phenol-water extraction. The extract was treated with RNase I. The
      carbohydrate containing-antigen (Ag-CHO) was immunogenic to rabbits and showed at
      least a fraction with some negative charge at pH 8.2. This antigen showed cross
      reactivity with the phenol-water extract of the growth medium used for the
      culture of promastigotes and with the surface antigens of promastigotes. Its
      composition is: 24.3% of total sugars, from which 11.2% of galactose, 7.5% of
      mannose and 5.6% of ribose. Protein content was 5.4% and phosphate 18.5%. The
      antigenic activity was maintained after: repeated freezing-thawing;
      lyophilization; heating at 100 degrees C for 30 minutes; treatment with RNase,
      trichloroacetic acid and sodium metaperiodate. The precipitin line obtained is
      Periodic Acid Schiff positive. The application of the Ag-CHO in
      counterimmunoelectrophoresis reaction for the immunodiagnosis of ACL showed 60%
      sensitivity, and no cross-reaction with the five sera of Chagas' disease patients
      tested. The use of this antigen in a more sensitive technique, with more samples
      of sera, may improve these results.

PMID- 8525272
TI  - A large epidemic of dengue fever with dengue hemorrhagic cases in Ceara State,
      Brazil, 1994.

PMID- 8525273
TI  - Bacterial antigen detection in cerebrospinal fluid by the latex agglutination
      test.
AB  - Eighty purulent cerebrospinal fluid (CSF) samples from patients with clinical
      evidence of meningitis were studied using the Directigen latex agglutination (LA)
      kit to determine the presence of bacterial antigen in CSF. The results showed a
      better diagnostic performance of the LA test than bacterioscopy by Gram stain,
      culture and counterimmunoelectrophoresis (CIE), as far as Neisseria meningitidis
      groups B and C, and Haemophilus influenzae type b are concerned, and a better
      performance than bacterioscopy and culture considering Streptococcus pneumoniae.
      Comparison of the results with those of culture showed that the LA test had the
      highest sensitivity for the Neisseria meningitidis group C. Comparing the results
      with those of CIE, the highest levels of sensitivity were detected for N.
      meningitidis groups B and C. Regarding specificity, fair values were obtained for
      all organisms tested. The degree of K agreement when the LA test was compared
      with CIE exhibited better K indices of agreement for N. meningitidis groups B and
      C.

PMID- 8525274
TI  - Paracoccidioidomycosis associated with acquired immunodeficiency syndrome. Report
      of seven cases.
AB  - We report the clinical findings and evolution of seven patients (five men and two
      women), the majority of them intravenous drug users, with paracoccidioidomycosis
      associated to acquired immunodeficiency syndrome (AIDS). In four of the patients
      the paracoccidioidomycosis was restricted to the lung and in the three others was
      generalized with cutaneous involvement. Only two of them had lived recently in
      rural area, an indication of the possible reactivation of latent focal infection
      in the other five patients. The recognition of the role of cell-mediated immunity
      in host defense against Paracoccidioides brasiliensis leds to the prediction of a
      growing occurrence of the paracoccidioidomycosis-AIDS association in areas that
      are endemic for these diseases.

PMID- 8525275
TI  - Subcutaneous hyalohyphomycosis caused by Acremonium recifei: case report.
AB  - We present a case of subcutaneous hyalohyphomycosis due to Acremonium recifei, a
      species whose habitat is probably the soil, first identified in 1934 by Area Leao
      and Lobo in a case of podal eumycetoma with white-yellowish grains and initially
      named Cephalosporium recifei. A white immunocompetent female patient from the
      state of Bahia, Brazil, with a history of traumatic injury to the right hand is
      reported. The lesions was painless, with edema, inflammation and the presence of
      fistulae. Seropurulent secretion with the absence of grains was present.
      Histopathological examination of material stained with hematoxylin-eosin showed
      hyaline septate hyphae. A culture was positive for Acremonium recifei. Treatment
      with itraconazole, 200 mg/day, for two months led to a favorable course and cure
      of the process. We report for the first time in the literature a case of
      subcutaneous hyalohyphomycosis due to Acremonium recifei in a immunocompetent
      woman. Treatment with itraconazole 200 mg/day, for two months, resulted in cure.

PMID- 8525276
TI  - [Chagas infection in university students].

PMID- 8525277
TI  - [Report of a case of dracunculosis in a dog in the Province of Formosa-
      Argentina].
AB  - It is reported Dracunculus sp. in a dog from Fontana city, department of Patino,
      in the Formosa Province, Argentina. This is the fourth report of Dracunculosis
      occurred in animals all from the same geographic area of Formosa.

PMID- 8525278
TI  - Schistosomiasis: predisposing cause for the formation of hepatic abscesses? Case
      report.
AB  - An adult patient with chronic schistosomiasis from an endemic area, complained
      about a seven day fever, along with jaundice and lumbar backache on the right
      side. Image exams showed multiple pyogenic liver abscesses. All the classic
      etiologies were discarded through clinical, radiological and laboratorial
      criteria. Schistosomiasis can cause pylephlebitis as a complication, along with
      immunesuppression, granulomatous reaction with central lobular liver necrosis and
      a greater risk of infection. The authors suggest that schistosomiasis in its
      chronic form may be the predisposing cause of multiple pyogenic liver abscesses,
      especially in endemic areas.

PMID- 8525279
TI  - Mechanical transmission of Trypanosoma spp. by African Stomoxyinae (Diptera:
      Muscidae).
AB  - Ten taxa of Stomoxyinae were tested for their ability to transmit Trypanosoma
      brucei, T. vivax, T. evansi and T. congolense to mice within 3 min of interrupted
      feeding on highly parasitaemic blood. T. brucei was the easiest parasite to
      transmit with an 11.5% success rate, followed by T. vivax at 3.4%, and T. evansi
      at 0.9%. T. congolense was not transmitted in 129 attempts. Stomoxys niger sspp.
      and four unstudied species (S. varipes, S. taeniatus, S. pallidus, Haematobosca
      squalida) were capable of transmitting trypanosomes mechanically.

PMID- 8525280
TI  - The duration of the cyst stage and the viability and virulence of Acanthamoeba
      isolates.
AB  - The viability of Acanthamoeba cysts after they have been stored in water at 4
      degrees C for a period of 24 years was determined and to estimate their present
      degree of virulence as compared to its primary values. The viability of 17
      amoebae isolates was examined using the eosin exclusion and in vitro excystation
      on agar plates (NNE). After the period of 24 years, only 3 isolates were found
      dead. The remaining 14 isolates after inoculation on NNE gave rise to new
      subcultures, although the percentage of living cysts measured by eosin exclusion
      was low (0-5%). Separate groups of mice were inoculated intranasally with 10
      subcultures characterised by varying primary virulence. It was found that in 8
      groups the mice were invaded (at varying degree), and some of them died. Taking
      into consideration the fact that some of the examined isolates completely lost
      their virulence only after 8 years of the in vitro cultivation, the obtained
      results are very intriguing. On the ground of these results one can assume that
      in the natural environment the period of viability for a cyst may be not shorter
      than 25 years, and, which is even more essential, they can maintain their
      invasive properties.

PMID- 8525281
TI  - Opportunistic and non-opportunistic parasites in HIV-positive and negative
      patients with diarrhoea in Tanzania.
AB  - A survey on intestinal parasites in a rural area of Tanzania revealed the
      presence of eight protozoa and seven helminths in 287 subjects (81.8%). The
      prevalence of Entamoeba histolytica and Ascaris lumbricoides was higher in HIV
      negative than in HIV-positive patients (P < 0.01; P < 0.04) (25.1% and 12.5% for
      E. histolytica; 10.5% and 3.7% for A. lumbricoides). On the other hand,
      Cryptosporidium parvum, Isospora belli and Strongyloides stercoralis prevalence
      was higher in HIV-positive than in HIV-negative patients (P < 0.01). The
      prevalence of these two opportunistic protozoa was also higher in AIDS patients
      than in HIV-positive patients without AIDS. Specific anti-C. parvum IgG were
      detected by ELISA in 18% and 56% of HIV-negative and positive patients,
      respectively, confirming the high number of contacts between this parasite and
      humans. Specific anti-Encephalitozoon cuniculi and anti-Encephalitozoon hellem
      IgG were detected by IFA in 18% and 19% of subjects, respectively, without any
      correlation with HIV and malaria infections.

PMID- 8525282
TI  - Evaluation of Fasciola excretory-secretory (E/S) product in diagnosis of acute
      human fasciolosis by IgM ELISA.
AB  - Diagnosis of fasciolosis in the acute phase depends on a sensitive and accurate
      serological test. The present study is an evaluation of the efficacy of excretory
      secretory Fasciola gigantica adult worm antigen by IgM ELISA. Thirty eight
      patients with acute fasciolosis and 14 in the chronic phase together with 23
      patients with different parasitic infections were introduced in the study.
      Seventeen healthy, parasite free individuals, were served as controls. A crude
      excretory-secretory antigen and its fractions I and II (obtained by gel
      filtration chromatography on Sephadex G-200) were tested. The crude antigen
      revealed 100% sensitivity, 94% specificity and 98% accuracy at the cut off level
      of 0.3 in acute infection. It gave positive results in 77% of chronic cases.
      Cross reactions with Schistosoma and Toxoplasma were negligible. A significant
      positive correlation between IHA titres and ELISA O.D. readings was observed.
      Fractions I and II proved of no diagnostic significance. The test system F.
      gigantica E/S product by IgM ELISA is highly recommended for diagnosis of acute
      fasciolosis.

PMID- 8525283
TI  - Amplification and characterization of cysteine proteinase genes from nematodes.
AB  - In order to isolate proteinase genes from parasitic nematodes by polymerase chain
      reaction (PCR) techniques, we employed a pair of consensus oligonucleotide
      primers designed to anneal to the active site cysteine (primer ncpC) and
      asparagine (primer ncpN) coding regions of cysteine proteinases. The primers were
      biased toward the nucleotide and codon usages of cysteine proteinase genes of
      nematodes and were based on the consensus nucleotide sequences flanking the
      active site residues of genes from Haemonchus contortus, Caenorhabditis elegans,
      and Ostertagia ostertagi. We employed 'touchdown' PCR conditions and were able to
      amplify novel cysteine proteinase gene fragments from the rodent parasite
      Strongyloides ratti, the human pathogen S. stercoralis, the canine hookworm
      Ancylostoma caninum, and from C. elegans. These clones are gene homologs of
      cathepsin B-like (lysosomal associated) proteases and will facilitate screening
      of both cDNA and genomic DNA libraries.

PMID- 8525284
TI  - A putative protein related to human chemokines encoded antisense to the cDNA of
      an Onchocerca volvulus antigen.
AB  - Chronic hyperactive dermatitis (sowda) in humans infected with the filarial
      parasite Onchocerca volvulus appears to reflect a hyperresponsiveness to parasite
      antigens. To identify antigens which play a role in this hyperresponsiveness an
      expression cDNA library of adult O. volvulus was screened with sera from patients
      with sowda. One further characterized cDNA clone, S1, consisting of 723 bp,
      surprisingly shows open reading frames (ORF) in both orientations. While a single
      ORF of 171 amino acids is present in sense orientation, a putative ORF of 95 AA
      is found in antisense orientation (aS1). Whereas no homologies to known proteins
      are found in S1, the sequence of aS1 shows a striking structural homology to
      human CC chemokines. The genomic organization of the coding region of aS1 shows
      the conserved three exon/two intron structure of the CC chemokine family. In
      adult worms transcription of mRNA corresponding to S1 but not to aS1 was
      detected. Expression of S1 as a non fusion protein and Western blot analysis
      revealed antibody recognition by all sera from patients with sowda, by 60% of
      sera from patients with the generalized form of onchocerciasis, but not by sera
      of exposed individuals with no evidence of onchocerciasis. IgG subclass analysis
      showed that IgG3 reactivity was restricted to sowda sera. In adult worms the S1
      protein was localized to the hypodermis. Here we present the cloning and
      characterization of an O. volvulus antigen, which may be useful in the diagnosis
      of onchocerciasis. Furthermore, the results suggest the presence of a gene
      structurally related to human inflammatory cytokines in antisense orientation,
      raising the question of bidirectional transcription in O. volvulus.

PMID- 8525285
TI  - The chemotherapy of onchocerciasis. XIX: The clinical and laboratory tolerance of
      high dose ivermectin.
AB  - Ivermectin is the drug of choice for the treatment of onchocerciasis. However at
      the recommended dose of 150 micrograms/kg, it neither kills nor permanently
      sterilises the adult worms. We investigated whether high doses given with and
      without a preceding 150 micrograms/kg 'clearing' dose would be tolerable as well
      as effective against the adult worms. Seventy-five healthy males with moderate to
      heavy infections with Onchocerca volvulus were enrolled in a double-blind trial
      to receive one of the following treatment regimens: 150 micrograms/kg followed by
      placebo (9 patients); 400 micrograms/kg with (9 patients) or without (16
      patients) a clearing dose; 600 micrograms/kg with (8 patients) or without (16
      patients) a clearing dose and 800 micrograms/kg with (8 patients) or without (9
      patients) a clearing dose. Detailed examinations were conducted before and at
      various times after treatment. A preliminary report on the clinical and
      laboratory safety as at 30 days is presented. All the regimens were well
      tolerated. No clinical or laboratory drug related effects were observed. The
      overall severity of the Mazzotti reaction was similar in all groups. Ocular
      reactions were minimal and there were no changes in ocular function or in
      fluorescein angiograms. The groups were similar in the extent of microfilaricidal
      activity; there was however a suggestion that microfilariae were killed more
      rapidly at 400 micrograms/kg and 600 micrograms/kg but not at 800 micrograms/kg.
      This needs further study. Single doses of ivermectin up to 800 micrograms/kg are
      well tolerated; no special precautions for treatment monitoring are required and
      a 'clearing' dose is not necessary.

PMID- 8525286
TI  - Pathogenicity of Artyfechinostomum oraoni in naturally infected pigs.
AB  - In an attempt to establish the diarrhoeogenic potential of the newly identified
      Artyfechinostomum oraoni, which was associated with human diarrhoea in a tribal
      community near Calcutta, India, two naturally infected domestic pigs of the
      locality were followed in captivity. Both pigs developed fatal diarrhoea after 5
      months. The autopsy revealed a massive infection with the echinostome on a
      haemorrhagic and oedematous mucosa of the jejunum and duodenum extending up to
      pyloric end of the stomach. It is suggested that similar pathology might also be
      operating in the infected man.

PMID- 8525287
TI  - Use of BCG in high prevalence areas for HIV.
AB  - Recommendations state that, where the risk of tuberculosis is high, BCG should be
      administered to infants as early in life as possible, even if the mother is known
      to be HIV-infected. BCG should be withheld from individuals with symptomatic HIV
      infections. However, continuing reports from sub-Saharan Africa and elsewhere of
      BCG complications in HIV-infected persons call for a re-assessment of current
      vaccination policies. For HIV-infected infants any benefit of BCG vaccination may
      be marginal because the prognosis is very poor. It is however not possible to
      exclude HIV-infected children from BCG vaccination at birth. HIV-uninfected
      infants born to HIV-infected mothers are at great risk of tuberculosis infection,
      which justifies routine vaccination. BCG rarely causes serious complications.
      Theoretically, persons with asymptomatic HIV infection may be at greater risk of
      complications from BCG vaccines, but available data are inconclusive in that
      respect. To vaccinate children with BCG at one year of age does not seem feasible
      and would increase the risk of tuberculosis especially for uninfected infants of
      HIV seropositive mothers. Available data seem to indicate that routine
      vaccination of newborns is indeed safe, even in areas with high prevalence of HIV
      infection.

PMID- 8525288
TI  - Relationship of antibodies to soluble Plasmodium falciparum antigen (Pf70) and
      protection against malaria in a human population living under intense
      transmission in Kinshasa, Zaire.
AB  - The rapid acquisition of resistance by Plasmodium falciparum to antimalarial
      drugs has focused worldwide efforts on vaccine development. The definition of
      critical antigens involved in the induction of protective immunity against
      disease is essential. Our previous studies have characterized a synthetic peptide
      complex (SPf70), derived from a 70 kDa P. falciparum exoantigen, in terms of its
      immunogenicity and antigenic reactivity. In the present study total anti-P.
      falciparum asexual blood-stage antibodies and antibodies to the Pf70 antigen were
      measured by immunofluorescence (IFA) and ELISA, respectively, in children and
      adults (n = 160) of Kinshasa, Zaire, an area with continuous and intense malaria
      transmission. All of the subjects tested had IFA antibodies and 90% (143/160) had
      antibodies to Pf70 antigen. Antibody levels against Pf70 were significantly
      higher among children with low parasitemias (p < 0.05). These results suggest
      that antibodies to Pf70 antigen may have a protective role against P. falciparum
      infection. Further studies are needed to define the functional nature of the
      protective mechanism(s).

PMID- 8525289
TI  - Malaria epidemiology in the province of Moyen Ogoov, Gabon.
AB  - In the course of epidemiological and immunological baseline studies
      parasitological surveys were conducted, in 1992, in three localities situated in
      our near rain forest in the area of Lambarene, Gabon, western Central Africa.
      Anopheles gambiae s.s. and A. funestus are considered to be the main vectors of
      malaria. The three localities represent strata with obvious differences in the
      intensity of malaria transmission. The lowest parasite rates were recorded in the
      village around the Albert-Schweitzer-Hospital where environmental sanitation and
      easy access to diagnostic and therapeutic facilities afford a fair measure of
      malaria control. The villages of Bellevue and Tchad show a much higher prevalence
      of Plasmodium falciparum, followed by P. malariae and P. ovale. In all three
      villages parasite rates and geometric mean parasite densities of P. falciparum
      showed the age pattern typical for areas with stable, hyperendemic malaria.
      Analysis by season showed the period of the long rains to be the
      epidemiologically calmest while the dry season and even more the short rainy
      season produced an increase of parasite rates and densities. In Tchad, the most
      affected of the three villages, the parasite rates in female adults were
      significantly lower than in male adults. This was accompanied by lower parasite
      densities in female adults.

PMID- 8525290
TI  - Evaluation of resistant-reversal, CDRI compound 87/209 and its possible mode of
      action in rodent experimental malaria.
AB  - The resurgence of malaria in form of resistance against chloroquine (CQ) has
      decreased the importance of the drug as a chemotherapeutic agent. If an agent in
      combination with CQ can make CQ resistant plasmodia susceptible to CQ, the
      problem of drug resistance may then be solved. Use of conventional drugs like
      verapamil, desipramine along with CQ suggested the feasibility of this approach.
      This report is concerned with a new class of compound, CDRI compound 87/209 (15
      mg/kg b. wt.) which is given in combination with chloroquine (10 mg/kg b. wt.)
      for 10 consecutive days to chloroquine resistant P. berghei/P. yoelii nigeriensis
      (multidrug resistant) infected Mastomys coucha/Swiss albino mice respectively,
      displayed a potential in curing the animals. A tentative mode of action of the
      CDRI compound 87/209 based upon its unique property of inhibiting heme-oxygenase
      (a heme degrading enzyme) has been presented. It is likely that CDRI compound
      87/209 in combination with chloroquine may reverse the resistance acquired by the
      malarial parasites and in combination with CQ is capable of clearing the parasite
      from the animals.

PMID- 8525291
TI  - The antimalarial drug, Ro 42-1611 (arteflene), does not affect cytoadherence and
      cytokine-inducing properties of Plasmodium falciparum malaria parasites.
AB  - The purpose of this study was to investigate the ability of the antimalarial
      drug, Ro 42-1611 to block parasite mediated cytokine induction in vitro as well
      as cytoadherence of infected erythrocytes to melanoma cells in vitro. The
      biological activity of Ro 42-1611 was confirmed as it blocked Plasmodium
      falciparum growth in cultures. Ro 42-1611, had no major effect on TNF, IL-alpha
      or IL-6 cytokine release from mononuclear cells stimulated with malaria antigens
      or lipopolysaccharide and it did not affect cell viability. Ro 42-1611 only
      slightly suppressed cytoadherence of infected erythrocytes to melanoma cells. The
      therapeutic effect of To 42-1611 appears to be confined to its parasite killing
      activity.

PMID- 8525292
TI  - Trypanosoma evansi: measurement of pyruvate production as an indicator of the
      drug sensitivity of isolates in vitro.
AB  - In a previous study, three in vitro methods for the assessment of drug
      sensitivity among Trypanosoma evansi isolates were compared--a direct counting
      method, pyruvate production method and uptake of radiolabelled hypoxanthine. The
      pyruvate assay system, which measures the amount of pyruvate in the supernatant
      of growing populations of trypanosomes by a spectrophotometric method, was
      selected for further investigation with regard to its suitability for field
      studies. The effect of initial seeding density and incubation time on the growth
      of three stocks of T. evansi--TREU 1840 and TREU 1981 (suramin sensitive) and
      TREU 2136 (suramin resistant)--and drug sensitivities revealed by the pyruvate
      assay and direct counting were examined to optimise assay conditions. Maximum
      densities and pyruvate production achieved were not affected by varying the
      initial seeding densities in the range of 5 x 10(4)-5 x 10(5)/ml and had been
      reached after 48 hours incubation with one exception: Pyruvate levels continued
      to increase up to 72 hours in the suramin resistant stock. However, inhibition
      curves were affected by initial seeding density and incubation period. Results
      suggested that an initial seeding density of 1 x 10(5)/ml and an incubation time
      of 48 hours are optimal for the assay. Using these assay conditions, the isolates
      were screened against suramin, quinapyramine sulphate and Cymelarsan, the
      trypanocides used most commonly against T. evansi. This assay proved to be a
      relatively simple and cheap technique applicable to screening large numbers of
      isolates of differing sensitivities to trypanocidal drugs.

PMID- 8525293
TI  - The chemotherapeutic efficacy of diminazene aceturate and lithium chloride
      against relapse infection of Trypanosoma brucei brucei in rats.
AB  - The chemotherapeutic efficacy of diminazene aceturate (Berenil) and lithium
      chloride (LiCl) in relapse infection of trypanosomiasis was investigated in rats
      experimentally infected with Trypanosoma brucei brucei. The study showed that the
      combination of diminazene aceturate at (7 mg/kg) and LiCl (10 micrograms/kg)
      appeared more effective therapeutically than diminazene aceturate, or diminazene
      aceturate and LiCl and dexamethasone group, as more of the rats in the diminazene
      aceturate and LiCl treated-group remained aparasitaemic for longer days (60
      days). Relapse parasitaemia occurred on days 10 and 12 in diminazene aceturate (7
      mg/kg); diminazene aceturate (7 mg/kg) and LiCl (10 micrograms/kg) plus
      dexamethasone (1 mg/kg) treated group respectively, while relapse parasitaemia
      did not occur in the diminazene aceturate and LiCl treated group until day 20.
      Histopathological examination of the brain did not show any signs of inflammatory
      reaction in the diminazene aceturate and LiCl and dexamethasone treated group.
      However lesions associated with meningoencephalitis, such as cellular
      infiltration of mononuclear cells, perivascular cuffings and perivascular
      congestion and oedema were observed in the diminazene aceturate; diminazene
      aceturate and LiCl treated groups.

PMID- 8525294
TI  - [Cell transformation].
AB  - The use of in vitro cell transformation, as a complement to the direct study of
      tumors and established tumor cell lines, has enabled the analysis of the
      contribution of diverse genes to the tumor phenotype. The most recent results
      have underlined the importance of fundamental mechanisms regulating cell
      proliferation. The role in the long term survival of mammalian cells in culture
      and in tumor progression of the telomerase enzyme, which permits the maintenance
      of chromosome ends integrity, has now been demonstrated. Cell cycle progression
      and its regulation are ensured by a positive control exerted by cyclin-kinase
      complexes and by a negative one exerted by kinase inhibitors. Cyclin and kinase
      genes are frequently altered in transformed and tumor cells, as well as the genes
      coding for membrane proteins responsible for cell-cell and cell-matrix contacts.

PMID- 8525295
TI  - [Oncogenes and their discovery].
AB  - Oncogenes have been discovered through the study of oncogenic retroviruses. Viral
      oncogenes present in the viral genome are the genes responsible for the
      transforming properties of these viruses. Viral oncogenes are altered forms of
      cellular genes, designated as proto-oncogenes, that have been transduced into the
      genome of transforming retroviruses. Deregulated expression or structural
      alteration of cellular proto-oncogenes by amplification, mutation or
      translocation has been implicated in the occurrence of human cancers.

PMID- 8525296
TI  - [Abnormal signal transduction and cancer].
AB  - Molecules involved in communication and signal transduction play a key role in
      the control of cell growth and differentiation. Growth factors are
      multifunctional regulatory peptides acting through membrane receptors, a number
      of which has tyrosine kinase activity. Downstream, cytoplasmic substrates
      transduce the signal to the nucleus. This cascade can be altered by structural
      mutations or by deregulation and thus participate to tumorigenesis.

PMID- 8525297
TI  - [Genetic predisposition to cancer development].
AB  - In less than ten years, the study of inherited conditions predisposing to cancer
      led to major discoveries on the basic mechanisms of carcinogenesis. Those
      investigations have permitted to discover a new class of cancer genes now named
      "suppressor" genes (or antioncogenes), and to demonstrate their implication in
      the majority of cancer including the sporadic one's. Those studies have indicated
      that familial forms of cancer can also result from alterations of a set of genes
      controlling genomic stability. In clinical practice, the identification of the
      molecular basis of major forms of inherited predisposition to cancer, has allowed
      to better define those cancer syndromes. As a consequence, it is now possible to
      propose to the at risk individuals, and their families, screening protocols based
      on precise estimate of their genetic risk.

PMID- 8525298
TI  - [Genetic instability and cancer].
AB  - Multiple mutations are present in most human tumours. These genetic modifications
      appear to be necessary to produce and select pretumoral, tumoral and metastatic
      clones. These multiple mutations can be sequentially produced by genotoxic agents
      leading to cancers with a long latency period or due to mutations in genes
      implicated in the control of the genetic stability. Several human diseases are
      linked with a very high cancer incidence because they are hereditarily carrying a
      mutation on some DNA repair genes, mismatch repair genes or tumour suppressor
      genes. These abnormal functions will produced a mutator phenotype leading to a
      cascade of genetic modifications which will allow the rapid production of cancer
      cells.

PMID- 8525299
TI  - [Apoptosis and cancer].
AB  - Apoptosis is a mode of active cell death having distinct biochemical and
      morphological features including chromatin condensation, polynucleosomal DNA
      fragmentation, and disruption of cells into apoptotic bodies. The apoptotic
      process plays a major role both during development and in the functioning of the
      immune system. Apoptosis may in part be genetically regulated, and may also be
      linked to physiological and non physiological signals from the environment.
      Apoptosis may be a defense at the cellular level against cancer. Moreover, there
      is evidence that a number of pro-oncogenes and tumor suppressor genes are
      involved in regulating apoptosis. Further understanding of the molecular events
      underlying the apoptotic process should provide new insights into the mechanism
      of tumorigenesis and facilitate the development of new strategies for the
      treatment of cancer.

PMID- 8525300
TI  - [Metastatic process].
AB  - The metastatic dissemination is one characteristic property of malignant tumors.
      It represents a crucial step in the progression of the disease. Multiple cellular
      and molecular mechanisms are involved in the dissemination of cancer cells and
      their proliferation at secondary sites. The metastatic process requires the
      transient or permanent acquisition of invasive properties mediated in part by
      diverse families of proteases. Numerous growth factors control the autocrine or
      paracrine growth of the tumor. These factors can also act as motogens and may
      contribute to the maintainance of the loss of the differentiated state of tumors.
      Angiogenesis of newly formed primary tumors is required for further growth and
      dissemination. Malignant cells modulate their adhesive status throughout the
      different steps of dissociation from the primary tumor and their intravasation
      and extravasation from lymph and blood vessels. Proteases, adhesion molecules,
      growth factors, angiogens and their cognate receptors may constitute markers to
      assign a metastatic phenotype and could serve as targets for the management of
      patients.

PMID- 8525301
TI  - [Tumor cell antigenicity: cancers and vaccines].
AB  - Tumor-specific immunity is partly linked to the observation that cancerous cells
      express some proteins that are not present in normal cells. In the past, one of
      the major problems for the development of immunotherapy approaches has been
      linked to the difficulty to identify the antigens which are the targets of the
      tumor-specific T cells. Recent progress in fundamental immunology, particularly
      concerning the understanding of the molecular basis of cellular immunity, has
      facilitated the identification of tumor-specific antigens. These results allow to
      study new therapeutic approaches today.

PMID- 8525302
TI  - [Gene therapy of cancer].
AB  - Therapeutic gene transfer for cancer can aim at different goals, the main of them
      being: 1. to increase anti-tumor cell immune response; 2. to introduce a drug
      activating gene into tumor cells; 3. to normalize cell cycle by inhibiting
      oncogenes or transferring antioncogenes. Significant, sometimes spectacular
      results have been reported using models of transplantation of tumor cell lines to
      animals, but not yet with spontaneous animal tumors. Although most of the about
      130 clinical trials of gene therapy authorized around the world are devoted to
      cancer, it is so far impossible to predict the future of this strategy, and when,
      if any, it will succeed.

PMID- 8525303
TI  - [Non-insulin-dependent diabetes. Epidemiology, etiology, physiopathology,
      diagnosis, complications, prognosis, treatment].

PMID- 8525304
TI  - [Upper and lower urinary tract infections. Epidemiology, etiology,
      physiopathology, diagnosis, development, treatment].

PMID- 8525305
TI  - [Chronic duodenal ulcer. Diagnosis, development, treatment].

PMID- 8525306
TI  - [Anaphylactic shock. Physiopathology, diagnosis, treatment and posology].

PMID- 8525307
TI  - [Acute inflammatory polyradiculoneuritis (Guillain-Barre syndrome). Diagnosis,
      development, prognosis].

PMID- 8525308
TI  - [Leishmania braziliensis: isolation from lesions by inoculation of hamsters with
      and without addition of salivary gland lysate from Lutzomyia youngi].
AB  - Homogenized biopsy tissue from the cutaneous leishmaniasis lesions of 50 patients
      from Trujillo, Venezuela, were inoculated subcutaneously into the tarsi of male
      hamsters. Homogenized tissue either alone or mixed with salivary gland lysates of
      Lutzomyia youngi were used for inoculation. Homogenized tissue alone yielded
      58.5% of infections with a mean of twelve weeks for prepatency, while those mixed
      with sandfly lysate resulted in 92% of infections with a mean prepatency of three
      weeks.

PMID- 8525309
TI  - Duration of larval and pupal development stages of Aedes albopictus in natural
      and artificial containers.
AB  - Aedes albopictus were reared in different containers: a tree hole, a bamboo stump
      and an auto tire. The total times from egg hatching to adult emergence were of
      19.6, 27.3 and 37.5 days, respectively, according to the container. The first,
      second and third-instar larvae presented growth periods with highly similar
      durations. The fourth-instar larvae was longer than the others stages. The
      pupation time was longer than the fourth-instar larvae growth period. The
      temperature of the breeding sites studied, which was of 18 degrees C to 22
      degrees C on average, was also taken into consideration. The mortality of the
      immature stages was analysed and compared as between the experimental groups; it
      was lower in the natural containers than in the discarded tire. The average wing
      length of adult females emerging from tree hole was significantly larger (p <
      0.05) than that of those emerging from the tire.

PMID- 8525310
TI  - Studies on mosquitoes (Diptera: Culicidae) and anthropic environment. 7-behaviour
      of adults Nyssorhynchus anophelines with special reference to Anopheles
      albitarsis s.l. in south-eastern Brazil.
AB  - Results obtained with catches performed at several sites of the Ribeira Valley,
      SP (Brazil) are reported. Collections with Shannon type traps showed a
      concentration of An.albitarsis s.l. in the Experimental Farm of Pariquera-Acu
      County, associated with the development of irrigated rice cultivation. Two
      species of the complex, named A and B, were recognized. Species B predominated in
      the samples. Indoor and outdoor crepuscular human bait captures were performed a
      the domiciliary environment. The two species showed a generally low William's
      media valve of 0.2, the highest value obtained was 1.6. No differences were found
      between indoor and outdoor behaviours between the two species of the complex.

PMID- 8525311
TI  - Risk factors for basal cell carcinoma: a case-control study.
AB  - A controlled trial was performed with the purpose of investigating which factors
      could be considered of significant risk for the development of basal cell
      carcinoma. A total of 259 cases of basal cell carcinoma diagnosed from July 1991
      to July 1992 were compared with 518 controls matched for age and sex. All
      subjects in both groups were white. Protocol data were submitted to statistical
      analysis by the chi-square test and by multiple conditional logistic regression
      analysis and the following conclusions were reached: 1) light skin color (types I
      and II of the Fitzpatrick classification), odds ratio of 2.8; outdoor work under
      constant sunlight, odds ratio of 5.0; the presence of actinic lesions due to
      exposure to the sun, odds ratio of 4.9, are risk factors per se. 2) Type III skin
      in the Fitzpatrick classification only represents a risk factor when the patient
      reports a history of intense sunburns, but not in the absence of such a history.
      3) Sunburns per se do not represent a risk factor althorig the point made in item
      2 of these conclusions is valid. 4) Other suspected risk factors whose
      significance was not confirmed by multiple conditioned logistic regression
      analysis were: residence in rural areas, light eyes and blond hair color, extent
      of the awareness of the "sun x skin cancer" relationship, familial occurrence of
      skin cancer, excessive exposure to the sun, and freckles appearing in childhood.

PMID- 8525312
TI  - Smoking, consumption of alcohol and sedentary life style in population grouping
      and their relationships with lipemic disorders.
AB  - The study, part of the project "Atherosclerotic cardiovascular diseases, lipemic
      disorders, hypertension, obesity and diabetes mellitus in a population of the
      metropolitan area of the southeastern region of Brazil", had the following
      objectives: a) the characterization and distribution among typical human socio
      economic groupings, of the prevalence of some particular habits which constitute
      aspects of life-style-the use of tobacco, the use of alcohol and sedentary
      activity; b) the establishment of the interrelation between the above-mentioned
      habits and some lipemic disorders. The prevalence of the habits cited behaved in
      the following manner: the use of tobacco predominated among men, distributed
      uniformly throughout the social strata; among the women the average percentage of
      smokers was 18.9%, a significant difference occurring among the highest socio
      economic class, where the average was of 40.2%. The sedentary style of life
      presented high prevalence, among both men and women with exception of the women
      of the highest socio-economic level and of the skilled working class. The use of
      alcohol, as one would expect, is a habit basically practised by the men, without
      any statistically significant differences between classes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8525313
TI  - [Prevalence of smoking and associated factors in a metropolitan area in the
      southern region of Brazil].
AB  - A cross-sectional study was carried out for the purpose of evaluating, the
      prevalence of smoking and the factors associated with it in Porto Alegre, a city
      in southern Brazilian. Through proportional, multiple stage, random sampling,
      1.091 individuals (92% of those eligible) of 18 or more years of age, were
      interviewed at home. Exposure to smoking was measured by a questionnaire that
      inquired about the type, quantity and frequency of tobacco use. The prevalence of
      smoking was 34.9% (CI 31.9-37.8). It was higher -among men--41.5% (CI 38.5-44.4)
      then women--29.5% (CI 26.8-32.2). The former started smoking at mean age of 16
      (+/- 5.6), with mode of 15 and smoked an average of 19.0 (+/- 14.0) cigarettes
      per day. Females started at a mean age of 17.8 (+/- 6.7), with mode of 14 years
      old and smoked 14.5 (+/- 10.3). The association of the drinking habit and
      demographic and socioeconomic variables with smoking was evaluated through
      logistic regression. The variables included in the model were sex, age,
      education, income, professional qualification and alcohol consumption. The
      prevalence of smoking was greater for men, individuals of lower socioeconomic
      level, between 30 and 39 years of age, and among those accustomed to consuming
      alcoholic beverages. In conclusion, this study demonstrated that smoking is a
      public health problem in Brazil as in another countries. It is associated with
      sex, age, education and professional qualification, as has been observed
      elsewhere. The association of alcohol consumption with smoking may be understood
      as risk behavior, both having similar determinants.

PMID- 8525314
TI  - [The social geography of AIDS in Brazil].
AB  - The first of a series of papers concerning the evaluation of the dynamics of the
      AIDS epidemic in Brazil employing techniques of geographical analysis, is here
      presented. Results of research undertaken in the US (especially in New York City)
      are compared with those of a recent investigation carried out in the city of
      S.Paulo, Brazil (Grangeiro, 1994). In both, geographical patterns of socio
      demographic variables correlate with different patterns of the spread of the AIDS
      epidemic through the transmission groups. Recent trends of the AIDS epidemic in
      Brazil: the displacement toward medium sized cities and expansion frontiers,
      increasing report of AIDS cases among the poor and underprivileged, changes in
      the pattern of transmission with proportional augmentation of heterosexual
      transmission and IDUs as transmission groups, are described and analysed. The
      geographical distribution of the AIDS cases registered between 1987-1993 in
      Brazil throughout the Brazilian States is evaluated by means of worksheets, maps,
      and non-parametric statistics. Results show that Gravimetric Centers (obtained by
      the use of the calculus spatial means) of AIDS in Brazil are situated within a
      triangle the sides of which are formed lines joining the three main metropolitan
      areas of the wealthiest region of Brazil--the southeast, i.e. Sao Paulo, Rio de
      Janeiro and Belo Horizonte. These especially S. Paulo, function as points of
      attraction for these Gravimetric Centers (GCs) towards the south as compared with
      the GCs of the general population calculated ia accordance with data from the
      1980 and 1991 censuses. It is possible to observe a displacement of the GCs
      toward the northwest over this period in accordance with the migration patterns
      of the Brazilian population in general, though with a dynamic of its own. These
      changes in the geographical, socio-demographic and transmission group patterns
      show the complex nature of the epidemic in Brazil and pose additional
      difficulties for the development of prevention strategies.

PMID- 8525315
TI  - [Culicidae of Itaipu lake, in the Parana river, southern Brazil].
AB  - Mosquito catches were made in Guaira county, Parana State, southern Brazil, in
      the vicinity of Itaipu dam, from January to December 1991. The catches were made
      with a Shannon light trap and human bait. The Shannon light trap was installed
      beside the highway that used, formerly, to lead to the Sete Quedas cataracts and
      the human bait was used in the urban area. Data about the Culicidae fauna were
      obtained as to predominant species, seasonal variation, time of highest density
      and affinity with human host. Forty-one species were identified as belonging to
      the Anopheles, Aedes, Aedomyia, Coquillettidia, Culex, Mansonia, Psorophora and
      Uranotaenia genera. With the Shannon light trap 21,280 mosquitoes were caught and
      with human bait 1,010. In the catches made with the Shannon light trap,
      Coquillettidia shannoni, Mansonia humeralis, Anopheles trianulatus, Aedes
      scapularis and Anopheles albitarsis accounted for 82.78% of all mosquitoes taken.
      In the catches made on human bait the highest densities of these mosquitoes
      occurred between 7 p.m. and 9 p.m. Aedes scapularis, Mansonia humeralis and
      Anopheles albitarsis represented 91.21% of all mosquitoes caught with human bait.
      The highest densities of Aedes scapularis, on human bait, were found between 8
      p.m. and 9 p.m. and those of Mansonia humeralis and Anopheles albitarsis between
      6 p.m. and 7 p.m. Among the genera caught with the Shannon light trap
      Coquillettidia shannoni, Mansonia humeralis and Anopheles albitarsis were most
      frequent in April, Anopheles triannulatus in January and Aedes scapularis in
      February.

PMID- 8525316
TI  - [Qualitative research in health: methodological reflections on the oral report
      and narrative production in a study about the medical profession].
AB  - Qualitative research as applied to Public Health and Social Medicine is studied.
      The project is based upon research into the historical transformation of medical
      professional autonomy as medicine shifted from the "liberal" practice to recent
      "technological" medicine. Field research used unstructured recorded interviews to
      gather personal testimonies about the professional histories of physicians who
      graduated between 1930 and 1955. These testimonies are technically classified as
      "oral accounts" and were registered as free narratives. This study analysis how
      accounts can express the physicians' self-representations of their daily work and
      simultaneously write the history of medical practice. Further, the unstructured
      interview is evaluated as an instrument yielding free narratives and life
      accounts.

PMID- 8525317
TI  - [Hydrogen peroxide as despyrogenation agent for medical and hospital product
      components].
AB  - The current search for alternative solvents to fluorinated products, in face of
      the depletion of ozone in the stratosphere calls for the development of
      alternative processes applicable to the manufacture of medical devices. In view
      of the challenge and as water is serving particularly as the choice for other
      industrial segments, the fast macrobial proliferation in it is of concern, as it
      is a potential source of endotoxins. Such a risk is inconsistent with the
      production of items designed for example, for use in surgical procedures in the
      cardio-vascular field. Thus research was undertaken for the purpose of
      investigating the possibility of using water as a cleansing agent for components
      for such products, providing that hydrogen peroxide is added. The work was
      carried out by inoculating water and peroxide at levels of 0.1, 0.25, 0.5 e 1.0
      UE/ml. The confirmation was obtained as to the active effectiveness at a 5%
      concentration of hydrogen peroxide by means of analytical determination using the
      "in vitro" method. The effectiveness of the use of peroxide was investigated on
      polycarbonate injected parts designed for the manufacture of oxigenators and
      blood reservoirs and contained with endotoxins. The findings permit one to draw a
      favorable conclusion regarding the adequacy of the proposed process both
      biologically as well as regards the removal of impurities.

PMID- 8525318
TI  - Studies on mosquitoes (Diptera: Culicidae) and anthropic environment. 8--Survey
      of adult behaviour of Spissipes Section species of Culex (Melanoconion) in south
      eastern Brazil.
AB  - A study of Spissipes Section of Culex (Melanoconion) adults behaviour was carried
      out from August 1992 through December 1993 in human dominated (anthropic)
      environment in the Ribeira Valley, S. Paulo State, Brazil. By sampling at several
      sites it the dominance of Culex ribeirensis and Cx. sacchettae became evident
      even through a total number of ten species was recorded. Those two mosquitoes
      showed a clear tendency to frequent the domiciliary environment where they were
      caught, both indoor and outdoor, through the use of the human bait. In the
      outside environments, the residual patchy forests seems to display a
      concentration role, from which these adults spread to the open land and reach the
      dwellings. As their vector competence has been demonstrated through the virus
      isolations in natural conditions, it is advisable to pay attention to the
      presence of these mosquitoes in the man-made environment.

PMID- 8525319
TI  - [Host preference of Culicidae (Diptera) collected in central Argentina].
AB  - In order to study the host preference of female mosquitoes, samples were taken
      fortnightly in Cordoba and Cosquin (Argentina), during October-April of two
      consecutive years. Four different vertebrates were used in baited-can traps:
      frogs, chickens, rabbits and turtles. The genus Culex accounted for 92.9% of the
      specimens collected. Aedes for 7.0% and Psorophora ciliata 0.02%. The highest
      proportion of females were collected in chicken traps (68.7%), followed by rabbit
      traps (29.9%), turtles (0.8%) and frogs (0.5%), thus the majority of the
      mosquitoes were collected in traps with homeotermous hosts. Only Culex dolosus
      fed on all the hosts. Culex acharistus, Cx. chidesteri and Cx. quinquefasciatus
      fed on chickens, rabbits and turtles. Aedes albifasciatus, Ae. scapularis, Cx.
      bidens and Cx. coronator fed on both homeotermous hosts. Culex apicinus, Cx.
      maxi, Cx. saltanensis and Cx. spinosus fed only on chickens and Ps. ciliata only
      on rabbits.

PMID- 8525320
TI  - [Comparison between the erythroimmunoadsorption test by capture, immunoenzymatic
      and passive hemagglutination tests used in the diagnosis of neurocysticercosis].
AB  - Comparisons were made among the erythroimmunoadsorption by capture (C-EIA), the
      immunoenzymatic (ELISA) and passive haemaglutination (P.H.A.) tests used in the
      diagnosis of neurocysticercosis. The three tests, two of them routine by in
      diagnosis, and the third one (C-EIA) recently, standardised were compared for the
      detection of anti-Cysticercus cellulosae antibodies. In the three reactions the
      antigen utilized was raw saline extract (R.S.E) with a yield of 0.1, 1 and 10
      micrograms protein/cavity for the C-EIA, ELISA and P.H.A tests, respectively. In
      a group of 58 patients with neurocysticercosis, the sensitivity to the ELISA, C
      EIA and P.H.A tests was of 98.2%, 84.5% and 77.2%, respectively. In the control
      group of 85 individuals, healthy or with encephalopathies other than
      neurocysticercosis, the sensitivity was of 98.27%, 84.48% and 79.63%,
      respectively, and the specificity was of 94.1%, 95.3% and 91.8%. This order of
      choice should be followed, depending on the resources available.

PMID- 8525321
TI  - [Nutritive value of collective meals: tables of food composition versus
      laboratory analysis].
AB  - A cycle of 13 basic meals lunches, planned and executed at an industrial feeding
      unit was studied, in order to verify the agreement between the nutritive value
      estimated by indirect analysis (Tables of chemical composition of foodstuffs),
      and by direct analysis in the laboratory. Two samples of each meal were taken,
      one consisting of raw unprocessed food and the other of prepared processed food.
      The following parameters were evaluated: weight, dry matter, humidity, proteins,
      lipids, fibers ashes, carbohydrates, calcium, iron and phosphorus. The results
      suggest that both the composition tables presented a weak correlation for calcium
      and phosphorus. Comparing processed with unprocessed meals, there was an increase
      in weight and humidity, and a considerable variation in protein, ash, iron and
      phosphorus, suggesting interference of the culinary process. The Food Composition
      Tables present limited reliability for the estimation of most nutrients in
      collective, prepared meals.

PMID- 8525322
TI  - [Food poisoning outbreak caused by Salmonella Enteritidis in the northwest of Sao
      Paulo State, Brazil].
AB  - A foodborne outbreak which affected 211 persons occurred, in a School, in 1993.
      The epidemiological data obtained by interviewing the affected and non affected
      persons sampled showed as predominant symptoms: diarrhoea, fever (77.7%),
      abdominal cramps (67.7%), vomiting (65.8%), hot-and-cold sensations (54.5%) and
      headache (44.5%). The median incubation period was of 17 hours, the limits being
      3 and 29 hours. The disease period was of from 3 to 4 days. The food concerned
      was a kind of pate, a mayonnaise mixture prepared with fresh eggs with boiled
      potatoes that was consumed with bread. The biological material analysis-3
      coprocultures, and leftovers of the food revealed the presence of one and the
      same organism: Salmonella Enteritidis. In the food, the numbers of this bacterium
      per gram were sufficient to account for the manifestation of the disease (10(4)
      and 10(5)g). The antibiogram of all th isolates showed the same sensibility
      pattern. The preparation related to this outbreak suggests the endogenous
      contamination of the eggs; the cross contamination-the outbreak affected three
      school periods, as the food was prepared separately for each school period; and
      the conditions under which the food was kept during the time from preparation to
      consumption. The observation of the 3 food handlers, by successive coprocultures,
      for one week, indicates that they were not asymptomatic carriers nor were they
      affected as a result of this outbreak by the causal bacteria.

PMID- 8525323
TI  - [Infant morbimortality due to acute diarrhea in a metropolitan area of
      northeastern Brazil, 1986-1989].
AB  - Six cross-sectional studies involving children under five years of age in three
      places on S. Luiz island, i.e., Vila Palmeira, Anjo da Guarda and S. Jose de
      Ribamar, were performed. A standardized questionnaire on the presence of
      diarrhoea in the previous 2 weeks was answered by the mothers or by those
      responsible for the children. Two population based studies (in May 1986 and May
      1989) and four sample based surveys (in November of 1986, 1987 and 1988 and in
      May 1989) were carried out. The prevalence of diarrhoea was highest in May, 1986
      and November, 1987. The highest prevalence occurred in S. Jose de Ribamar. The
      distribution of cases according to age showed a higher prevalence among children
      of 6-11 months and between 1 and 2 years of age. The prevalence of diarrhoea was
      highest among the families: that excreted directly into the sea or a latreen;
      that used water from uncovered wells; that threw their garbage into the sea; and
      whose bread-winners were unemployed. Diarrhoea was the principal cause of death
      in both surveys. Infant mortality, in May 1986, was 44.0 per thousand in children
      under 1 year of age and 12.8 in children under 5 years old; in May 1989 it was
      7.9 per thousand and 4.9 per thousand respectively. The decrease in child
      morbidity and mortality due to diarrhoea between 1986 and 1989 was statistically
      significant.

PMID- 8525324
TI  - [Isolation of rabies virus from the insectivorous bat Myotis nigricans].
AB  - The following is a case study of the natural infection by the rabies virus of an
      insectiverous bat belonging to the species Myotis nigricans in the municipality
      of Ribeirao Pires, Greater S. Paulo. Diagnosis was made by means of
      immunofluorescence and intracerebral innoculation of mice with nervous and
      intrascapular muscular tissues.

PMID- 8525325
TI  - [Malaria acquired during entomological research in the Serra do Mar, southeastern
      region of Brazil].
AB  - A focus of malaria was discovered at the beginning of 1993, in the Coastal Range
      State Park, in the Atlantic Forest area of the State of S. Paulo, Brazil. The
      entomological research carried out there caused malaria infection by Plasmodium
      vivax in three workers of the Endemic Research Control Superintendancy
      (Superintendencia de Controle de Endemias - SUCEN), of the State Health
      Secretariat. It is worth emphasizing that transmission occurred in an area which
      had been presenting low levels of incidence of the disease; also, the capturers
      who were undertaking their entomological activities in the area were exposed for
      an extremely short period of time in one case for only three hours.

PMID- 8525326
TI  - [Single larva sampling for Aedes aegypti surveillance].
AB  - Buildings in Araraquara city, Southeastern Brazil, were searched during a year
      for the presence of Aedes larvae using single larva sampling in order to check
      the single-larva methodology. In those breeding places in which Aedes larvae were
      found, one of them was collected. As a control, after the single larva had been
      collected, all the larvae from the breeding place were collected for later
      identification. This process was repeated in the laboratory. Of the 447 domiciles
      searched, 12 were considered positive and 20 breeding places were found. Of the
      breeding places, 13 contained Aedes larvae, 5 both Aedes and Culex larvae and 2
      Culex larvae only. The results show that all the breeding places in the field
      were properly recognized showing the method may be used for Aedes surveillance in
      cities infested with one species only or without any domiciliary infestation.

PMID- 8525327
TI  - [Theory and practice of alternative practice].
AB  - So-called alternative medical practices, now favored in Brazil, are discussed in
      terms of their methods and rationale. Cursory inquiries show that personal
      choices of diagnostic and therapeutic systems is made, usually, on the basis of
      family tradition, cultural inheritance, and fashion, and not upon a critical
      examination of the principles upon which the alternatives are based. In general,
      a syncretic approach combining conflicting elements from different systems is
      adopted. In contrast, the author shows that the actual differences between the
      systems lie in their foundations principles, not in their practices.

PMID- 8525328
TI  - [Legislation related to mental health: a review of various international
      experiences].
AB  - The main areas dealt with by current mental health legislation, worldwide, are
      reviewed. These areas concern mainly: (i) rights of the mentally ill (right to
      care and human rights), (ii) quality of care, (iii) the use of administrative and
      budget control measures, and (iv) consumer participation and involvement in the
      organization and management of mental health care services. The evolution of
      international legislation (particularly United Nations Declarations, Covenants
      and Resolutions) relative to people with mental disorders are described on the
      basis of up-to-date examples of legal models from different jurisdictions
      throughout the world. The main current trends are identified and alternatives are
      advanced for the respect of the human rights of these people and for the
      improvement of their care. The basis for these proposed alternatives is to be
      found in the recently approved United Nations General Assembly Resolution on "The
      protection of persons with mental illness and the improvement and the improvement
      of mental health care". This Resolution is described and discussed in some
      detail.

PMID- 8525329
TI  - [Research in public health].

PMID- 8525330
TI  - Description of Lutzomyia (Pifanomyia) robusta n. sp. (Diptera, Psychodidae,
      Phlebotominae) from Peruvian Equadorean interandean areas.
AB  - Description of Lutzomyia robusta, n. sp. (Diptera, Psychodidae, Phlebotominae)
      from interandean areas of Peru and Equador. Lutzomyia robusta, n. sp., probable
      vector of human bartonellosis and cutaneous leishmaniasis, is described and
      illustrated. This species presents strong affinity with L. serrana (Damasceno &
      Arouck, 1949) but they can be distinguished by variance analysis of four male
      characteristics and only one female characteristic. In the variance analysis,
      populations of L. serrana, of Amazonian areas of Brazil, Peru and Bolivia, the
      coast of Equador and other areas of Brazil were studied. The synonymy of
      Lutzomyia guayasi (Rodriguez) and L. serrana was corroborated.

PMID- 8525331
TI  - [Does the new Health Insurance Legislation lead to more competition? Consequences
      for physicians].
AB  - One of the goals of the new Swiss Health Insurance Law, which will be effective
      as of January 1, 1996, is to strengthen the market forces in the Swiss health
      care system. Although under the new law several barriers to competition will
      continue to exist, competition between physicians in private practice and between
      hospitals will have profound effects. In future physicians will have to accept
      responsibility not only for medical aspects but also for the financial
      consequences of their action. They will be confronted with new forms of
      reimbursement, utilization and cost reviews. Therefore, doctors will require
      training for their new role in a market-oriented health care system.

PMID- 8525332
TI  - Any need for guidelines in the management of chronic obstructive pulmonary
      disease (COPD)?

PMID- 8525333
TI  - [Guidelines for the diagnosis and treatment of chronic obstructive lung disease-
      effective and necessary].
AB  - The independent practice of the art of medicine which doctors took for granted in
      the past has ended. With almost revolutionary speed, insurers, administrators and
      politicians have distributed the unique relationship between doctors and their
      patients. Treatment and diagnostic guidelines in different clinical entities have
      been based on the pillars of medicine - controlled studies and/or a common
      consensus among specialists and practitioners. These dynamic activities have
      enriched our knowledge and practice of medicine. However, only the continuing
      direct collaboration of physicians at all levels and constant adjustment to
      changing conditions make these guidelines applicable to the ever changing world
      of medicine. Chronic obstructive lung disease is one such clinical entity that
      requires uniform guidelines. Issues that have to be addressed are not only who
      belongs in this category but also what interventions, such as lateral chest
      radiographs, CT scans and sleep lab investigations, should be performed as well
      as the indications for costly therapies such as long-term home oxygen, alpha-1
      protease inhibitor augmentation therapy and lung transplantations. Instead of
      looking at guidelines at straitjackets that limit excellence in the practice of
      medicine, medical associations should treat them as an opportunity to define
      their own quality standards. By doing so, the medical community would eliminate
      the influence of administrative directions or gatekeeper decisions, while
      patients and the whole population would greatly benefit.

PMID- 8525334
TI  - [A brief plea against the use of guidelines in medicine].
AB  - The use of guidelines in medical practice may be dangerous since it limits the
      art of medicine to the mere observance of rules. Some aspects of guidelines do
      not rely on scientific knowledge, but on a democratic approach (panel of
      specialist!). Finally, guideline users expose themselves to the pressure of
      communities, health care systems or possible legal action. These are risks which
      cannot justifiably be incurred.

PMID- 8525335
TI  - [Various new pathogens in pneumonia].
AB  - The table summarizes the many newly recognized agents causing lower respiratory
      tract infections: gram + cocci, Streptococcus agalactiae, enterococci; gram-rods,
      acinetobacter, Aeromonas hydrophila, Eikenella corrodens; Mycobacterium
      tuberculosis resistant to multiple drugs, intracellular organisms and viruses.
      Some details are given in four chapters: Pneumococci resistant to penicillin G
      which must be detected and impose new therapeutic strategies; Chlamydia
      pneumoniae with its difficulties for the diagnosis and the absence of
      standardized therapeutic trials; Streptococcus pyogenes with a recrudescence of
      severe and invasive infections, TSS and virulence factors; the pulmonary
      Hantavirus syndrome with 105 patients recognized (mortality 52%) in the USA and
      Canada, the homeland of the deermouse (Peromiscus maniculatus).

PMID- 8525336
TI  - Human host response to Mycobacterium tuberculosis.
AB  - Despite the importance of tuberculosis as the leading cause of death due to
      infectious disease in the world, it has only been recently that an understanding
      of the human host response in this infection has begun to emerge. The key
      components of this response are cytokines and components of cellular immunity,
      predominantly T-lymphocytes and macrophages. Though the relationships among the
      components of the immune response are complex, it seems likely that in response
      to mycobacterial infection associated with active disease, cytokines such as TNF
      alpha and IL-1 beta are produced; these cytokines serve to recruit more
      lymphocytes, generally of the T(H) (T helper) phenotype, which then produces
      substances such as the macrophage activating factor interferon-gamma. Macrophages
      activated by IFN-gamma ar thus stimulating to enhance intracellular killing of
      mycobacteria. The role of other cytokines, such as IL-6 and IL-8, both of which
      are induced by M. tuberculosis or its cell was components, is less clear. Further
      elucidation of the human host response to tuberculosis should help in the
      development of new vaccines and treatment strategies.

PMID- 8525337
TI  - [Volume reduction surgery--a new treatment concept in advanced diffuse pulmonary
      emphysema].
AB  - Excision of large space occupying bullae in patients with emphysema is an
      accepted procedure if the underlying parenchyma is compressed and relatively
      normal. This operation may relieve symptoms of dyspnea and improve exercise
      tolerance. The volume reduction operation is based on different concept and
      designed for the diffuse type of emphysema. Resection of the most diseased lung
      in patients with marked hyperinflation may relieve thoracic distension and
      improve respiratory mechanics. We are currently evaluating prospectively the use
      of bilateral thoracoscopic volume reduction for patients with advanced, diffuse
      emphysema. During the last 1 1/2 years over 20 patients have been operated on.
      The average FEV1 was 765 ml/sec preoperatively and improved 40% within 3 months
      with a range of 0-100%. The 12 minute walking distance improved more than 100%.
      There was no perioperative mortality. Bilateral thoracoscopic volume reduction
      surgery is a palliative procedure but offers significant improvement in pulmonary
      function and exercise capacity for many patients.

PMID- 8525338
TI  - [Cough--work-up and therapy].
AB  - Cough is one of the most prevalent symptoms of bronchopulmonary diseases. If
      cough persists ( > 6 weeks), further workup is mandatory. The most common causes
      of persistent cough in nonsmokers presenting with a normal CXR are postnasal drip
      due to chronic rhinitis-sinusitis, cough equivalent asthma or gastroesophageal
      reflux. The response to empirical therapy may confirm one of these etiologies.
      Other causes of chronic cough need further extensive workup involving radiologic,
      functional and endoscopic procedures.

PMID- 8525339
TI  - [Education of respiratory physiology in 2nd-year medicine: current challenges].
AB  - The author describes some of the challenges which face present day teaching in
      respiratory physiology. These are 1. poor integration with basic science, 2. non
      homogeneity of units and nomenclature, and 3. insufficient integration with what
      is taught in the third year. The author is optimistic about problem-oriented
      teaching integrating the first 3 years of medical school as a single whole.

PMID- 8525340
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Experimental
      studies on the cardiovascular effects of the blood pressure-lowering
      hydrazinophthalazine derivatives apresoline and nepresole. 1953].

PMID- 8525341
TI  - [Hemolytic anemia, myocardial infarction and xenotransplantation: what do they
      have in common?].
AB  - Complement is activated by antibodies, by necrotic cells and by the many surfaces
      which do not inhibit the amplification loop of the alternative pathway. Examples
      of such activation include hyperacute rejection in xenotransplantation models
      (antibody), myocardial infarction (necrotic cells) and paroxysmal nocturnal
      hemoglobinuria (PNH: lack of complement control on abnormal erythrocytes and
      platelets). Over the past decade many of the complement regulatory proteins have
      been described, analyzed and produced in recombinant forms. One of these proteins
      is complement receptor 1 (CR1, CD35), which in soluble form is capable of
      inhibiting complement activation in vivo. In many experimental models, soluble
      CR1 has been shown to reduce antibody-mediated damage, diminish inflammation at
      the time of cell necrosis and inhibit lysis of PNH cells. For the first time it
      will be possible to inhibit complement activation in humans.

PMID- 8525342
TI  - [Prospective therapy study in differentiated thyroid carcinoma].
AB  - Controversy still exists regarding the appropriate treatment for differentiated
      thyroid carcinoma, i.e. the extent of surgery and the usefulness of prophylactic
      131I thyroid ablation. However, the debate is nowadays confined to those patients
      who may be categorized as having a favorable prognosis with respect to tumor
      related death or serious recurrence, and the point of discussion is essentially
      the optimal treatment to prevent curable recurrences. From the literature it may
      be deduced that patients with a node negative papillary tumor of stage I and II
      in the age-related TNM classification system, and patients with a minimally
      invasive follicular carcinoma, have an excellent prognosis with respect to
      survival and recurrence. In a prospective study during a 20-year period from one
      surgical and one pathological institution 136 consecutive patients were treated.
      Patients with an incidental pT1 N0 tumor, or with a stage I or II node negative
      papillary carcinoma, or with a minimally invasive follicular carcinoma
      respectively, had a reduced extent of treatment. This consisted in resection for
      the concomitant benign goiter (7%), hemithyroidectomy (32%), or total
      thyroidectomy without 131I ablation (18%). All other patients, including those
      with a node positive tumor in stage I or II, had total thyroidectomy and 131I
      ablation (43%). Patients with a multifocal tumor had total thyroidectomy with or
      without 131I ablation. Hemi- or total thyroidectomy was technically carried out
      by capsular dissection with identification of the parathyroids, as introduced by
      Kocher and Halsted. Peritracheal and -laryngeal nodes were regularly searched
      for, and functional neck dissection was done in node positive tumors. Total
      thyroidectomy was carried out by completion thyroidectomy in 29 (35%) of the 83
      patients. 5 patients (7%) with papillary carcinoma, all in stage III or IV, and 5
      patients (8%) with follicular carcinoma, all with a high degree of capsular angio
      invasion, died from the tumor 6 months to 16 years after diagnosis. A further
      patient with a high degree follicular carcinoma is alive with residual disease.
      All these patients with an unfavorable course underwent total thyroidectomy and
      131I ablation as initial therapy. Two patients with papillary carcinoma had a
      presumptively curable recurrence, namely, a node recurrence in a pT1 N1 tumor
      (following total thyroidectomy and radio-iodine ablation), and a contralateral
      recurrence after hemithyroidectomy in a pT2 N0 tumor in a young patient. In sum,
      in no case with an unfavorable course was a radical therapy omitted initially,
      and less than total thyroidectomy with 131I ablation (n = 77 [57%]) led to a
      (curable) recurrence in only one instance (1.3%).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8525343
TI  - [Complex partial seizures as cause of transient cardiac arrhythmia].
AB  - The frequency and type of seizure-induced cardiac arrhythmias is presented in
      light of 36 partial-complex seizures recorded with simultaneous EEG/ECG. An
      average increase in heart rate of 35% (sinus tachycardia) was observed in 60% of
      patients (22/36). Bradycardia was demonstrated in 17% (6/36) due to AV-block in 3
      cases, once due to sinus bradycardia and once due to bradycardia in the presence
      of atrial fibrillation. In one patient with a pacemaker spontaneous heart rhythm
      ceased. The average slowing of heart rate was 29% with a maximum of 62.5%. In the
      remaining 23% of patients (8/36), no change in heart rate was observed. These
      results, in conjunction with those of the literature, indicate that a primary
      epileptic origin needs to be included in the differential diagnosis of cardiac
      arrhythmias.

PMID- 8525344
TI  - [Pruritus--also a challenge in internal medicine].
AB  - Generalized or localized itch without primary skin manifestations may be the
      presenting symptom of serious internal diseases. Five characteristic cases of
      pruritus are discussed: Hodgkin's disease, primary sclerosing cholangitis,
      polycythemia vera, iron deficiency (with pica), and uremia. Other important
      causes must be considered; all forms of cholestasis, including primary biliary
      cirrhosis, drug-induced, pregnancy-related, and extrahepatic cholestasis; other
      hematologic and malignant disorders such as non-Hodgkin's lymphoma, leukemia,
      multiple myeloma, solid tumors, and myelodysplastic syndromes; metabolic and
      endocrine diseases, most notably diabetes mellitus, hyperthyroidism,
      hypothyroidism, and carcinoid syndrome; focal neurologic diseases such as brain
      tumors, cerebral infarctions and multiple sclerosis; adverse drug reactions
      without rash; infectious diseases, especially parasitic and HIV infections. A
      diagnostic laboratory screening for pruritus of undetermined origin is suggested.

PMID- 8525345
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Chronic
      interstitial nephritis in abuse of phenacetin-containing analgesics (Saridon
      etc.) 1953].

PMID- 8525346
TI  - Crime and punishment. Meeting on genes and behavior gets only slightly violent.

PMID- 8525347
TI  - The struggle within. Conflict between fetus and mother may trouble pregnancy.

PMID- 8525348
TI  - Cystic fibrosis.

PMID- 8525349
TI  - How breast milk protects newborns.

PMID- 8525350
TI  - The puzzle of conscious experience.

PMID- 8525351
TI  - Treatment of migraine during pregnancy and lactation.
AB  - Migraine onset, frequency and severity are influenced by hormonal changes
      throughout the various female reproductive life events, including pregnancy.
      Migraine may worsen during the first trimester, but usually improves thereafter.
      The treatment of migraine during pregnancy and lactation is difficult because of
      the risks to the fetus and newborn. This paper reviews migraine throughout the
      female reproductive life events, as well as the acute and prophylactic treatment
      of the pregnant and lactating migraineur.

PMID- 8525352
TI  - Heparin dosing.

PMID- 8525353
TI  - Avoiding--and defending--allegations of inappropriate physician conduct. Midwest
      Medical Insurance Company Risk Management Committee.

PMID- 8525354
TI  - Can household pets be used as reliable monitors of lead exposure to humans?
AB  - We investigated the validity of dogs and cats as sentinels of environmental lead
      exposure to humans. This paper reports findings from a study conducted in Granite
      City, IL, during the summer of 1991. At this site, a former secondary lead
      smelter had been in activity for more than 80 years. The smelter was shut down in
      1982. The surrounding area was found to be contaminated with lead, with soil lead
      concentrations above 5000 ppm in some places. The Illinois Department of Public
      Health conducted a survey in the community to determine the effects of lead on
      the local population. We sampled dogs and cats owned by these people. Our results
      suggest that living near a closed lead smelter, with heavy soil contamination,
      was not associated with high blood lead concentrations in pets, or their owners.
      There was a significant relationship between BLC (blood lead concentrations), in
      indoor pets and younger children, which was consistent with our hypothesis that
      pets could be used to monitor childhood lead exposure. We also found that, when
      there was one pet with a high BLC in a house, the likelihood of finding one
      person with a BLC above 10 micrograms/dl was significantly increased.

PMID- 8525355
TI  - Hazard to man and the environment posed by the use of urban waste compost: a
      review.
AB  - This review presents the current state of knowledge on the relationship between
      the environment and the use of municipal waste compost in terms of health risk
      assessment. The hazards stem from chemical and microbiological agents whose
      nature and magnitude depend heavily on the degree of sorting and on the
      composting methods. Three main routes of exposure can be determined and are
      quantified in the literature: (i) The ingestion of soil/compost mixtures by
      children, mostly in cases of pica, can be a threat because of the amount of lead,
      chromium, cadmium, PCDD/F and fecal streptococci that can be absorbed. (ii)
      Though concern about contamination through the food chain is weak when compost is
      used in agriculture, some authors anticipate accumulation of pollutants after
      several years of disposal, which might lead to future hazards. (iii) Exposure is
      also associated with atmospheric dispersion of compost organic dust that convey
      microorganisms and toxicants. Data on hazard posed by organic dust from municipal
      composts to the farmer or the private user is scarce. To date, microorganisms are
      only measured at composting plants, thus raising the issue of extrapolation to
      environmental situations. Lung damage and allergies may occur because of organic
      dust, Gram negative bacteria, actinomycetes and fungi. Further research is needed
      on the risk related to inhalation of chemical compounds.

PMID- 8525356
TI  - Collaboration and data sharing.

PMID- 8525357
TI  - Depicting epidemiology.

PMID- 8525358
TI  - Heso-no-O: a gift.

PMID- 8525359
TI  - Heso-no-O: a gift.

PMID- 8525360
TI  - Less hype, more biology needed for gene therapy.

PMID- 8525361
TI  - Clinton holds first AIDS summit.

PMID- 8525362
TI  - Chernobyl's thyroid cancer toll.

PMID- 8525363
TI  - The molecular biology of rice.

PMID- 8525364
TI  - Mechanisms of gene activation.

PMID- 8525365
TI  - Ethylene sensors: how perceptive!

PMID- 8525366
TI  - Reactive immunization.
AB  - For almost 200 years inert antigens have been used for initiating the process of
      immunization. A procedure is now described in which the antigen used is so highly
      reactive that a chemical reaction occurs in the antibody combining site during
      immunization. An organophosphorus diester hapten was used to illustrate this
      concept coined "reactive immunization." The organophosphonate recruited chemical
      potential from the immune response that resembled the way these compounds recruit
      the catalytic power of the serine hydrolases. During this recruitment, a large
      proportion of the isolated antibodies catalyzed the formation and cleavage of
      phosphonylated intermediates and subsequent ester hydrolysis. Reactive
      immunization can augment traditional immunization and enhance the scope of
      catalytic antibody chemistry. Among the compounds anticipated to be effective are
      those that contain appropriate reactive functionalities or those that are
      latently reactive, as in the mechanism-based inhibitors of enzymes.

PMID- 8525367
TI  - Multiple TAFIIs directing synergistic activation of transcription.
AB  - Coordinate activation of transcription by multiple enhancer binding factors is
      essential for the regulation of pattern formation during development of
      Drosophila melanogaster. Cell-free transcription reactions are described that
      recapitulate transcriptional synergism directed by the Drosophila developmental
      regulators Bicoid (BCD) and Hunchback (HB). Within the basal transcription factor
      complex TFIID, two specific targets, TAFII110 and TAFII60, served as coactivators
      to mediate transcriptional activation by these two enhancer binding proteins. A
      quadruple complex containing TATA binding protein (TBP), TAFII250, TAFII110, and
      TAFII60 mediated transcriptional synergism by BCD and HB, whereas triple TBP
      TAFII complexes lacking one or the other target coactivator failed to support
      synergistic activation. Deoxyribonuclease I footprint protection experiments
      revealed that an integral step leading to transcriptional synergism involves the
      recruitment of TBP-TAFII complexes to the promoter by way of multivalent contacts
      between activators and selected TAFIIs. Thus, the concerted action of multiple
      regulators with different coactivators helps to establish the pattern and level
      of segmentation gene transcription during Drosophila development.

PMID- 8525368
TI  - Efficient aldolase catalytic antibodies that use the enamine mechanism of natural
      enzymes.
AB  - Antibodies that catalyze the aldol reaction, a basic carbon-carbon bond-forming
      reaction, have been generated. The mechanism for antibody catalysis of this
      reaction mimics that used by natural class I aldolase enzymes. Immunization with
      a reactive compound covalently trapped a Lys residue in the binding pocket of the
      antibody by formation of a stable vinylogous amide. The reaction mechanism for
      the formation of the covalent antibody-hapten complex was recruited to catalyze
      the aldol reaction. The antibodies use the epsilon-amino group of Lys to form an
      enamine with ketone substrates and use this enamine as a nascent carbon
      nucleophile to attack the second substrate, an aldehyde, to form a new carbon
      carbon bond. The antibodies control the diastereofacial selectivity of the
      reaction in both Cram-Felkin and anti-Cram-Felkin directions.

PMID- 8525369
TI  - Shock-excited OH maser emission outlining the galactic center supernova remnant
      G359.1-0.05.
AB  - A search using the Very Large Array was performed for 1720-megahertz OH maser
      line emission from a number of nonthermal radio continuum sources in the galactic
      center region. The 1720-megahertz transition has recently been noted for its
      potential as a tracer of shock activity. The most striking result was the
      detection of extended 1720-megahertz OH maser emission, as well as a number of
      compact OH maser features, along the interface between a large-scale continuum
      shell (G359.1-0.5) and its surrounding ring of high-velocity molecular gas. The
      morphological correlation among the neutral gas, the nonthermal shell, and the
      maser features provides strong support for the hypothesis that the 1720-megahertz
      maser line of OH arises from gas shocked by the impact of the expanding supernova
      remnant into the molecular material. However, the radial velocities of the
      molecular cloud surrounding G359.1-0.5 are more negative than that of the OH
      maser spots by more than 50 kilometers per second. Here it is suggested that only
      the low-radial-velocity component of the carbon monoxide material at the limb of
      the remnant satisfies the physical conditions required for collisional pumping of
      the OH 1720-megahertz line behind the expanding shock front.

PMID- 8525370
TI  - A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21.
AB  - The rice Xa21 gene, which confers resistance to Xanthomonas oryzae pv. oryzae
      race 6, was isolated by positional cloning. Fifty transgenic rice plants carrying
      the cloned Xa21 gene display high levels of resistance to the pathogen. The
      sequence of the predicted protein, which carries both a leucine-rich repeat motif
      and a serine-threonine kinase-like domain, suggests a role in cell surface
      recognition of a pathogen ligand and subsequent activation of an intracellular
      defense response. Characterization of Xa21 should facilitate understanding of
      plant disease resistance and lead to engineered resistance in rice.

PMID- 8525371
TI  - An ethylene-inducible component of signal transduction encoded by never-ripe.
AB  - The ripening-impaired tomato mutant Never-ripe (Nr) is insensitive to the plant
      hormone ethylene. The gene that cosegregates with the Nr locus encodes a protein
      with homology to the Arabidopsis ethylene receptor ETR1 but is lacking the
      response regulator domain found in ETR1 and related prokaryotic two-component
      signal transducers. A single amino acid change in the sensor domain confers
      ethylene insensitivity when expressed in transgenic tomato plants. Modulation of
      NR gene expression during fruit ripening controls response to the hormone
      ethylene.

PMID- 8525372
TI  - Ethylene-binding sites generated in yeast expressing the Arabidopsis ETR1 gene.
AB  - Mutations in the ETR1 gene of Arabidopsis thaliana confer insensitivity to
      ethylene, which indicates a role for the gene product in ethylene signal
      transduction. Saturable binding sites for [14C]ethylene were detected in
      transgenic yeast expressing the ETR1 protein, whereas control yeast lacking ETR1
      showed no detectable ethylene binding. Yeast expressing a mutant form of ETR1
      (etr1-1) also showed no detectable ethylene binding, which provides an
      explanation for the ethylene-insensitive phenotype observed in plants carrying
      this mutation. Expression of truncated forms of ETR1 in yeast provided evidence
      that the amino-terminal hydrophobic domain of the protein is the site of ethylene
      binding. It was concluded from these results that ETR1 acts as an ethylene
      receptor in Arabidopsis.

PMID- 8525373
TI  - Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV
      suppressive factors produced by CD8+ T cells.
AB  - Evidence suggests that CD8+ T lymphocytes are involved in the control of human
      immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or
      by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1
      alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T
      cells. Two active proteins purified from the culture supernatant of an
      immortalized CD8+ T cell clone revealed sequence identity with human RANTES and
      MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both
      immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells
      was completely blocked by a combination of neutralizing antibodies against
      RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and
      MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV
      2, and simian immunodeficiency virus (SIV). These data may have relevance for the
      prevention and therapy of AIDS.

PMID- 8525374
TI  - Sodium uptake by puddling in a moth.
AB  - Male Lepidoptera commonly visit stands of water to drink, a behavior known as
      puddling. Males of the notodontid moth Gluphisia septentrionis routinely puddle
      for hours, imbibing hundreds of gut-loads and voiding the fluid as repetitive
      anal jets. Cationic analyses showed puddling to lead to systemic sodium gain, a
      potential benefit to Gluphisia, whose larval food plant is low in sodium. Male
      Gluphisia are specialized for puddling, possessing a wide oral slit and a highly
      expanded enteric surface. The acquired sodium is transferred to the female at
      mating, for eventual incorporation into the eggs. Sodium acquisition may be the
      primary function of puddling in Lepidoptera.

PMID- 8525375
TI  - Evidence for developmentally programmed transdifferentiation in mouse esophageal
      muscle.
AB  - Transdifferentiation is a relatively rare phenomenon in which cells of one
      differentiated type and function switch to a second discrete identity. In
      vertebrate embryos, smooth muscle and skeletal muscle are distinct tissues that
      arise from separate compartments of the mesoderm. The musculature of the mouse
      esophagus was found to undergo a conversion from smooth muscle in the fetus to
      skeletal muscle during early postnatal development. The switch from smooth to
      skeletal muscle features the transitory appearance of individual cells expressing
      a mixed phenotype, which suggests that this conversion is a result of programmed
      transdifferentiation.

PMID- 8525376
TI  - Crystal structure of the V alpha domain of a T cell antigen receptor.
AB  - The crystal structure of the V alpha domain of a T cell antigen receptor (TCR)
      was determined at a resolution of 2.2 angstroms. This structure represents an
      immunoglobulin topology set different from those previously described. A switch
      in a polypeptide strand from one beta sheet to the other enables a pair of V
      alpha homodimers to pack together to form a tetramer, such that the homodimers
      are parallel to each other and all hypervariable loops face in one direction. On
      the basis of the observed mode of V alpha association, a model of an (alpha
      beta)2 TCR tetramer can be positioned relative to the major histocompatibility
      complex class II (alpha beta)2 tetramer with the third hypervariable loop of V
      alpha over the amino-terminal portion of the antigenic peptide and the
      corresponding loop of V beta over its carboxyl-terminal residues. TCR
      dimerization that is mediated by the alpha chain may contribute to the coupling
      of antigen recognition to signal transduction during T cell activation.

PMID- 8525377
TI  - DNA template and activator-coactivator requirements for transcriptional synergism
      by Drosophila bicoid.
AB  - The template and coactivator requirements for synergistic transcription directed
      by a single activator, Bicoid (BCD), bound to multiple sites have been
      determined. Mutagenesis studies in combination with protein binding experiments
      and reconstituted transcription reactions identified two independent activation
      domains of BCD that target different coactivator subunits (TAFII110 and TAFII60)
      of the basal transcription factor IID (TFIID). The presence of both coactivators
      is required for BCD to recruit the TATA binding protein (TBP)-TAF complex to the
      promoter and direct synergistic activation of transcription. Thus, contact
      between multiple activation domains of BCD and different targets within the TFIID
      complex can mediate transcriptional synergism.

PMID- 8525378
TI  - Control of cell fate by a deubiquitinating enzyme encoded by the fat facets gene.
AB  - Ubiquitin is a highly conserved polypeptide found in all eukaryotes. The major
      function of ubiquitin is to target proteins for complete or partial degradation
      by a multisubunit protein complex called the proteasome. Here, the Drosophila fat
      facets gene, which is required for the appropriate determination of particular
      cells in the fly eye, was shown to encode a ubiquitin-specific protease (Ubp), an
      enzyme that cleaves ubiquitin from ubiquitin-protein conjugates. The Fat facets
      protein (FAF) acts as a regulatory Ubp that prevents degradation of its substrate
      by the proteasome. Flies bearing fat facets gene mutations were used to show that
      a Ubp is cell type--and substrate-specific and a regulator of cell fate decisions
      in a multicellular organism.

PMID- 8525379
TI  - Precise spatial positioning of chromosomes during prometaphase: evidence for
      chromosomal order.
AB  - The relative locations of several chromosomes within wheel-shaped prometaphase
      chromosome rosettes of human fibroblasts and HeLa cells were determined with
      fluorescence hybridization. Homologs were consistently positioned on opposite
      sides of the rosette, which suggests that chromosomes are separated into two
      haploid sets, each derived from one parent. The relative locations of chromosomes
      on the rosette were mapped by dual hybridizations. The data suggest that the
      chromosome orders within the two haploid sets are antiparallel. This chromosome
      arrangement in human cells appears to be both independent of cell type- and
      species-specific and may influence chromosome topology throughout the cell cycle.

PMID- 8525380
TI  - Diffusion across the nuclear envelope inhibited by depletion of the nuclear Ca2+
      store.
AB  - Intact, isolated nuclei and a nuclear membrane (ghost) preparation were used to
      study regulation of the movement of small molecules across the Xenopus laevis
      oocyte nuclear membrane. In contrast to models of the nuclear pore complex, which
      assume passive bidirectional diffusion of molecules less than 70 kilodaltons,
      diffusion of intermediate-sized molecules was regulated by the nuclear envelope
      calcium stores. After depletion of nuclear store calcium by inositol 1,4,5
      trisphosphate or calcium chelators, fluorescent molecules conjugated to 10
      kilodalton dextran were unable to enter the nucleus. Dye exclusion after calcium
      store depletion was not dependent on the nuclear matrix because it occurred in
      nuclear ghosts lacking nucleoplasm. Smaller molecules and ions (500-dalton
      Lucifer yellow and manganese) diffused freely into the core of the nuclear ghosts
      and intact nuclei even after calcium store depletion. Thus, depletion of the
      nuclear calcium store blocks diffusion of intermediate-sized molecules.

PMID- 8525381
TI  - A nucleic acid triple helix formed by a peptide nucleic acid-DNA complex.
AB  - The crystal structure of a nucleic acid triplex reveals a helix, designated P
      form, that differs from previously reported nucleic acid structures. The triplex
      consists of one polypurine DNA strand complexed to a polypyrimidine hairpin
      peptide nucleic acid (PNA) and was successfully designed to promote Watson-Crick
      and Hoogsteen base pairing. The P-form helix is underwound, with a base tilt
      similar to B-form DNA. The bases are displaced from the helix axis even more than
      in A-form DNA. Hydrogen bonds between the DNA backbone and the Hoogsteen PNA
      backbone explain the observation that polypyrimidine PNA sequences form highly
      stable 2:1 PNA-DNA complexes. This structure expands the number of known stable
      helical forms that nucleic acids can adopt.

PMID- 8525382
TI  - Solution structure of a cisplatin-induced DNA interstrand cross-link.
AB  - The widely used antitumor drug cis-diamminedichloroplatinum(II) (cisplatin or cis
      DDP) reacts with DNA, cross-linking two purine residues through the N7 atoms,
      which reside in the major groove in B-form DNA. The solution structure of the
      short duplex [d(CAT-AGCTATG)]2 cross-linked at the GC:GC site was determined by
      nuclear magnetic resonance (NMR). The deoxyguanosine-bridging cis
      diammineplatinum(II) lies in the minor groove, and the complementary
      deoxycytidines are extrahelical. The double helix is locally reversed to a left
      handed form, and the helix is unwound and bent toward the minor groove. These
      findings were independently confirmed by results from a phase-sensitive gel
      electrophoresis bending assay. The NMR structure differs markedly from previously
      proposed models but accounts for the chemical reactivity, the unwinding, and the
      bending of cis-DDP interstrand cross-linked DNA and may be important in the
      formation and repair of these cross-links in chromatin.

PMID- 8525383
TI  - Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production.
AB  - Immune responses dominated by interleukin-4 (IL-4)-producing T helper type 2
      (TH2) cells or by interferon gamma (IFN-gamma)-producing T helper type 1 (TH1)
      cells express distinctive protection against infection with different pathogens.
      Interleukin-4 promotes the differentiation of naive CD4+ T cells into IL-4
      producers and suppresses their development into IFN-gamma producers. CD1-specific
      splenic CD4+NK1.1+ T cells, a numerically minor population, produced IL-4
      promptly on in vivo stimulation. This T cell population was essential for the
      induction of IL-4-producing cells and for switching to immunoglobulin E, an IL-4
      dependent event, in response to injection of antibodies to immunoglobulin D.

PMID- 8525384
TI  - Use of NMR to detect water within nonpolar protein cavities.

PMID- 8525385
TI  - STM on wet insulators: electrochemistry or tunneling?

PMID- 8525386
TI  - 18S rDNA from lophophorates.

PMID- 8525387
TI  - Hormonal and pregnancy relationships to rheumatoid arthritis: convergent effects
      with immunologic and microvascular systems.
AB  - OBJECTIVE: To review sex hormones and rheumatoid arthritis (RA) and the
      interrelationships between hormonal, immunological, and vascular systems. DATA
      SOURCES: Publications detailing serum sex hormone levels and their HLA
      interactions, steroidogenesis, pregnancy, and therapeutic uses of sex hormones in
      RA. STUDY SELECTION: Controlled studies of sex hormone levels in RA patients not
      previously treated with glucocorticoids. DATA EXTRACTION: Mean (+/- SD) serum
      levels of dehydroepiandrosterone sulfate (DHEAS), testosterone (T), and estradiol
      (E2). DATA SYNTHESIS: Mean (+/- SD) levels were collated into tables for women
      with pre-versus postmenopausal onsets of disease and men. Data were also ordered
      across all study groups by increasing mean levels of the control subjects. Pooled
      data were summarized statistically, and major sources of variation between the
      studies were identified. CONCLUSIONS: Serum DHEAS, an adrenal androgen, was
      impressively decreased among women with premenopausal onset of RA. One study
      showed such deficiency years before disease onset. Serum T was somewhat decreased
      in the premenopausal onset group, but could be explained by decreased peripheral
      conversion of the lower levels of adrenal androgens. Women with postmenopausal
      onset of RA had modestly decreased serum DHEAS levels overall, but no difference
      in serum T, compared with controls. Male RA cases had consistently decreased
      serum levels of T, but not of DHEAS. Serum E2 was comparable in all RA versus
      control groups. The complex biology of pregnancy was interpreted as an example of
      vital interactions between hormonal, immunological, and vascular systems, as they
      may relate to the physiopathology of RA. The major age, sex, and hereditable
      determinants of RA were compared within a composite table of estimated relative
      risks. Elucidation of the interacting risk factors offers promising avenues of
      research in this complex disease.

PMID- 8525388
TI  - Epidemiology of systemic vasculitis: changing incidence or definition?
AB  - The epidemiology of the systemic vasculitides is poorly documented. Many studies
      have been conducted from tertiary referral centers, with resulting problems of
      referral bias and uncertainty of denominator population, or have involved small
      populations. We have estimated the incidence of the major forms of systemic
      vasculitis in a stable, ethnically homogeneous population of 414,000 adults from
      1988 to 1994. The overall annual incidence of systemic vasculitis (excluding
      giant cell arteritis) is 39/million (95% confidence intervals; ranging from 31 to
      47). The annual incidence of Wegener's granulomatosis is 8.5/million (range, 5.2
      to 12.9), Churg-Strauss syndrome 2.4/million (0.9 to 5.3), microscopic
      polyangiitis 2.4/million (0.9 to 5.3), adult Henoch-Schonlein purpura 1.2/million
      (0.3 to 3.5), and systemic rheumatoid vasculitis 12.5/million (8.5 to 17.7).
      These data suggest that the overall incidence of systemic vasculitis is greater
      than previously thought (10/million) with Wegener's granulomatosis and systemic
      rheumatoid vasculitis being the most common. Whether this represents a genuine
      increase in incidence or increased physician awareness is uncertain.

PMID- 8525389
TI  - Tumor-induced osteomalacia.
AB  - Tumor-induced (oncogenic) osteomalacia is a rare clinicopathologic entity in
      which the clinical signs and symptoms of osteomalacia and the specific laboratory
      abnormalities of hypophosphatemia, hyperphosphaturia, and low serum levels of
      1,25(OH)2 vitamin D are associated with the finding of a neoplastic process in
      the patient. To date, less than 100 cases of oncogenic osteomalacia have been
      described. We report a new case of adult-onset hypophosphatemic osteomalacia
      leading to the discovery of an asymptomatic phosphaturic mesenchymal lung tumor.
      Complete resection of the pulmonary neoplasia was followed by rapid normalization
      of the laboratory findings and clinical remission. The clinical, laboratory, and
      histopathologic spectrum of tumor-induced osteomalacia is presented, and the
      postulated mechanism of this condition is discussed in light of the relevant
      literature. The presence of occult neoplasms should be considered in cases of
      unexplained adult osteomalacia, with the physician's efforts being rewarded by
      the dramatic cure that follows excision of the tumor.

PMID- 8525390
TI  - Lupus in the 1980s: III. Influence of clinical variables, biopsy, and treatment
      on the outcome in 150 patients with lupus nephritis seen at a single center.
AB  - Of 500 patients with systemic lupus erythematosus observed at our center, 150
      fulfilled criteria for lupus nephritis. Of these 150 patients, 91% were female,
      and 67% were white. The mean age of onset was 26.2 years, and the mean follow-up
      duration was 11.7 years. Biopsies (n = 142) performed on 107 patients showed the
      following World Health Organization (WHO) class distribution: class I, n = 1;
      class II, n = 13; class III, n = 19; class IV, n = 69; class V, n = 17; class VI,
      n = 8; and class not determinable, n = 15. Ninety-five patients were nephrotic.
      Therapeutic intervention courses given to all patients (n = 356) included
      parenteral (IV) cyclophosphamide (n = 58), high-dose oral steroids (n = 126),
      pulse steroids (n = 49), apheresis (n = 39), azathioprine (n = 43), oral
      cyclophosphamide (n = 5), nitrogen mustard (n = 27), and chlorambucil (n = 6). In
      addition to examining the course of disease for various subsets, various
      predictors for fatality and end-stage renal disease (ESRD) were analyzed.
      Descriptive data for the short-term response to five therapies are provided for
      the complete patient sample, proliferative disease, and nephrotic syndrome.
      Twenty patients died, primarily from cardiovascular complications and sepsis,
      with 97% and 92% 5- and 10-year survival rates, respectively. Twenty-nine were
      dialyzed, and 11 were transplanted. Risk of ESRD by WHO class at 5 years was as
      follows: class III, 0%; IV, 9%; V, 16% (P = .04 for class V v other
      patterns).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525391
TI  - Synovial perfusion in the human knee: a methodologic analysis.
AB  - Synovial perfusion was quantified in milliliters per minute per knee by two quite
      different clearance methods based on (1) counting tritiated water in serial
      aspirates of intraarticular saline, and (2) external counting of joints injected
      with free radioiodide. In each case, the serial counting data determine a rate
      constant that is multiplied by a distribution volume to provide the clearance in
      flow terms of milliliters per minute. This report updates and summarizes these
      data and compares the two methods to each other and to alternative assessments of
      synovial blood flow. Available methods such as laser Doppler flowmetry (with data
      output measured in volts) and solute clearance constant determinations (in min-1)
      are useful for selected purposes but cannot be used to quantify the articular
      flux (in milligrams per minute) of any solute. Radiolabeled microspheres provide
      data (in milliliters per minute per g of tissue) but are unsuitable for human
      use. The two clearance methods provide comparable results, but the free iodide
      technique seems most suitable for physiologic investigations. The latter
      potentially includes critical evaluations of synovial blood flow in relation to
      issues such as palpable warmth, visible erythema, articular ischemia, the
      permeability of synovial vessels, the genesis of effusions, the delivery and
      removal of therapeutic agents, and the concentration of every synovial fluid
      solute from micronutrients through cytokines, plasma proteins, and molecular
      markers of cartilagenous injury.

PMID- 8525392
TI  - Peripheral ulcerative keratitis in the setting of rheumatoid arthritis: treatment
      with immunosuppressive therapy.
AB  - Peripheral ulcerative keratitis (PUK) is a rare but serious inflammatory eye
      condition that can complicate rheumatoid arthritis. PUK can be a warning sign of
      impending vasculitis, and cytotoxic therapy may be necessary to induce remission.
      We have encountered three patients with PUK in the past year. Two patients had
      long-standing quiescent rheumatoid arthritis who developed photophobia. Diagnosis
      was made by slit lamp examination. Treatment with local cyclophosphamide and
      prednisone resulted in prompt remission of the ulcer within 8 weeks. Cytotoxic
      therapy was discontinued altogether within 6 months. The third patient was also
      treated successfully with oral steroids and azathioprine. In all patients, sicca
      was noted. None of them had any evidence of systemic vasculitis. PUK, when
      recognized early and treated aggressively, can result in remission of the ulcer
      and in the prevention of vasculitis. Keratoconjunctivitis sicca can accompany PUK
      independent of the activity of rheumatoid arthritis.

PMID- 8525393
TI  - Health and human rights.

PMID- 8525394
TI  - An outbreak of hepatitis A in school children at Nakhon Si Thammarat, southern
      Thailand.
AB  - Hepatitis A antibody prevalence in Southeast Asia has markedly declined among
      children and adolescents. Therefore increasing a number of susceptible
      populations could result in an outbreak or epidemic. This paper reports an
      intensive study of an outbreak of hepatitis A in a primary school children during
      an endemic at Nakhon Si Thammarat, Southern Thailand. Eighty-nine children were
      inspected randomly from the total of 269 students, age ranged from 7-12 years
      old. The school children and parents were interviewed for their illness.
      Serological tests for antiHAV IgM and antiHAV (total antibody) were performed by
      ELISA. There were 36 cases of clinical acute hepatitis were positive for antiHAV
      IgM because of serological tests were performed nearly 4 months later. Seventy of
      89 children tested were positive for antiHAV and 16 of them were positive for IgM
      class. Seven of 16 children with antiHAV IgM positive were asymptomatic. The
      significant risk factors for children with positive antiHAV were occurrence of
      hepatitis patients in the family and no latrine (p < 0.01). Endemic transmission
      in this outbreak occurred rapidly. Therefore preventive measures are essential in
      reducing the infection rate. In addition to personal hygiene, immunoprophylaxis
      with either immunoglobulin or HAV vaccine is recommended.

PMID- 8525395
TI  - Prevalence of hemagglutination-inhibition and neutralizing antibodies to
      arboviruses in horses of java.
AB  - A study was conducted to measure the prevalence of hemagglutination-inhibition
      (HI) and neutralizing antibodies against two arboviruses (Chikungunya and
      Japanese encephalitis virus) in horses of Java, Indonesia. Blood specimens were
      collected from a sample of 112 horses at two stables: Pulo Mas, a racing track
      horse complex, located in a residential area in North Jakarta, and Pamulang, a
      riding school, located in a rural environment of West Jaya. Sera were tested by
      the HI assay and plaque reduction neutralization test. JEV antibodies were
      detected by HI in 58 (52%) of the horses, while only 11 (10%) had Chikungunya
      antibodies by HI. The proportion of Pamulang horses infected with JEV (66%) was
      significantly higher than found among Pulo Mas horses (40%) screened (p < 0.01).
      Of the 58 horses with JEV antibodies by HI, 52 (90%) were found to have specific
      neutralization antibodies to JEV. HI and neutralization tests on horse sera
      indicated that the risk to alpha virus infections was minimal in horses surveyed
      from Java. However, there was a high risk of JEV infection among the same
      population.

PMID- 8525396
TI  - Antibodies in serum of patients with clonorchiasis before and after treatment.
AB  - Sera of 31 patients infected with Clonorchis sinensis were examined using
      fraction 1 antigen by ELISA during a one-year observation. The results of ELISA
      with Igs, IgG and IgA demonstrated high sensitivity (100%, 100% and 90%) and
      specificity (100%, 100% and 87%). Sera specific Igs and IgG were significantly
      decreased in the 3rd month after treatment with praziquantel (25mg/kg body weight
      in one dose), and IgA was significantly decreased in the 1st month (paired t
      test, p < 0.05). No eggs were found in the stool after treatment. Detection of
      sera specific Igs, IgG and IgA by ELISA was combined with stool examination to
      evaluate the effect of praziquantel and the completeness of the cure.

PMID- 8525397
TI  - Plasma concentrations of praziquantel during the therapy of neurocysticerosis
      with praziquantel, in the presence of antiepileptics and dexamethasone.
AB  - Plasma praziquantel concentrations were measured in 11 Thai patients with active
      neurocysticercosis (8 males and 3 females). Praziquantel (Biltricide 600 mg per
      tablet) was given at a daily dose of 45 mg/kg given in 3 divided doses for 15
      consecutive days. All patients had significant improvement with resolution of
      symptoms and signs, and reduction of active lesions of cysticercosis shown by the
      brain computed tomographic scanning. After oral administration, the drug was
      rapidly absorbed from the gastrointestinal tract. There was substantial inter
      individual variability in plasma concentrations of praziquantel. After the first
      dose, maximum plasma concentrations in the range of 42-540 ng/ml was attained at
      30 minutes to 5 hours. In all cases, the drug almost totally disappeared from
      plasma within 8 hours; drug levels measured prior to the first doses on the
      following days showed undetectable levels. The area under the plasma
      concentration-time curves of praziquantel following the first dose were between
      125 and 990 ng hour/ml. The results suggested that the unusual low plasma
      availability of the drug observed in this group of patients could be a
      consequence of pharmacokinetic drug interactions of the concomitant therapy with
      antiepileptic drugs and dexamethasone. Active metabolite(s), rather than
      praziquantel itself, may play a significant part in the therapy of
      neurocysticerosis.

PMID- 8525398
TI  - Single doses of ivermectin 400 micrograms/kg-1: the most effective dosage in
      bancroftian filariasis.
AB  - Forty-three Wuchereria bancrofti carriers were given four successive semi-annual
      single doses of ivermectin 100 micrograms.kg-1 (IVER 100). The geometric mean
      microfilaremia (mf) recurrence percentage as compared to the pre-initial
      treatment mf level was 35%, 21%, 17% and 17% at 6, 12, 18 and 24 months,
      respectively. However, the recurrence of mf 6 months after the fourth treatment
      remained high in several individuals: 15 have been considered as 'bad responders'
      and 28 as 'good responders' individuals. At month 24 (M 24), they were randomly
      allocated into 2 groups. A first group was treated with a fifty and a sixth dose
      of IVER 100, at M24 and M30, respectively; the second one was treated, at the
      same time, with single doses of IVER 400 micrograms.kg-1 (IVER 400). At M 36, the
      mf recurrence percentage (mf M36/mf M0) was significantly higher in patients
      treated with IVER 100 than IVER 400 (11% vs 1%, p < 10(-4). From the group IVER
      100, 6 out of the 8 'bad responders' remained 'bad responders' whereas there were
      none of the 7 in the group IVER 400. Moreover, there were only 2 more patients in
      the group IVER 100 showing sustained complete zero mf, whereas they were 13 in
      the group IVER 400. Single doses of IVER 400 were effective on 'bad responders';
      IVER 400 must be recommended for semi-annual mass treatment in bancroftian
      filariasis.

PMID- 8525399
TI  - Anti-nematode activity of sixteen compounds against Trichinella spiralis in mice-
      a possible new screen for macrofilaricides.
AB  - There are few small animals models for filariasis, even more so for
      onchocerciasis. Therefore it is difficult to test under drug screening conditions
      large numbers of potentially macrofilaricidal compounds. One way around this
      difficulty is to use mice infected with Trichinella spiralis which by reason of
      anatomical location in the host would show some correlation in antinematode
      activity between the test and target organisms. This study investigated the
      activity of 16 compounds against the immature larval stage of T. spiralis. All
      the nine benzimidazole compounds (albendazole, flubendazole, mebendazole,
      oxfendazole, oxibendazole 780118, 780120, 790163, and 790392) were active, the
      most potent being oxfendazole. The benzothiazoles (CGP21306, CGP20376, CGP21833
      and CGP24588A) also indicated some anti-nematode activity together with 35vr, an
      imidazopyridine, but not as marked as the benzimidazole group. However, the
      organic arsenical compounds (Mel Ga and Mel Ni) showed little activity and this
      was at a rather highly toxic level. The prospects of using the Trichinella-mouse
      model as a primary screen to test for potential macrofilaricides are discussed.

PMID- 8525400
TI  - Prevalence of intestinal parasitic infections among Asian female house keepers in
      Abha District, Saudi Arabia.
AB  - A group of 5,518 female Asian house keepers working in Abha District of Saudi
      Arabia was examined (1990 through 1992) to determine the prevalence of intestinal
      parasitic infections. They came from Indonesia, Sri Lanka, Philippines and
      Thailand. Fresh stool specimens were obtained in special containers and examined
      by light microscopy of wet smears in normal saline and Lugoll's iodine solution
      within one hour of collection. The study revealed an overall prevalence of 46.5%
      which was higher than that reported among the Saudi population. The common
      parasites found included Trichuris trichiura (28.8%), Ascaris lumbricoides
      (22.2%), Hookworm (14.9%), Enterobius vermicularis (0.8%), Strongyloides
      stercoralis (0.6%), Entamoeba histolytica (1.2%), Hymenolepis nana (0.2%), and
      Giardia intestinalis (0.1%). The prevalence of intestinal parasites was
      statistically different among various studied nationalities. The possibility of
      spreading such diseases throughout the community should be considered in the
      light of the nature of work of this group being in close contact with different
      family members. It is recommended that all expatriate workers be checked and
      treated if necessary on arrival for the first time or from vacation. This policy
      must be strictly monitored, particularly for female house keepers.

PMID- 8525401
TI  - Urinary iodine excretion in the northeast of Peninsular Malaysia.
AB  - A total of 2,034 subjects aged 15 years and above from different parts of the
      State of Kelantan were studied to determine goiter size and urinary iodine
      excretion. The State was divided into 2 areas - area 1 consisting of localities
      in the districts near the coast and area 2 consisting of localities in the inland
      districts. There were 1,050 subjects in area 1 and 984 subjects in areas 2. The
      mean age (+/- SE) of subjects in areas 1 and 2 were 38.2 + 0.5 and 37.1 +/- 0.5
      years, respectively. The prevalence of goiter was 31.4% in area 1 and 45.0% in
      area 2; the difference was statistically significant (p < 0.05). However, the
      prevalence of large and visible goiters (grades II and III) was only 2.0% in area
      1 and 3.3% in area 2; the difference was not statistically significant. The mean
      (+/- SD) urinary iodine excretion in areas 1 and 2 was 57.1 +/- 2.1 and 56.8 +/-
      2.1 micrograms I/g Cr, respectively. The values were below those recommended by
      WHO. There was no significant difference in urinary iodine excretion between
      those with and without goiters in both areas and also between the grades of
      goiters. There were significantly more females with goiters than males in both
      areas but there was no significant difference in the urinary iodine excretion
      between the 2 sexes. Thus based on urinary iodine excretion, the iodine intake of
      the population in this area, was suboptimal and this was associated with a high
      prevalence of goiter.

PMID- 8525402
TI  - Effects of antithrombin III and antivenom on procoagulant activity of Russell's
      viper venom in a whole blood model.
AB  - The procoagulant activities of Russell's viper venom were assessed in an in vitro
      whole blood model. Sequential samplings showed that the generation of
      fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4
      (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an
      initial slow phase followed by a rapid phase of secretion. In the presence of
      Russell's viper venom, the generation of both FPA and PF4 was accelerated with
      the bi-phasic kinetics of PF4 being maintained while that of FPA completely
      disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin
      III (AT-III) had no antagonistic effect against the venom but combination of both
      resulted in a significant prolongation of both FPA and PF4 release (p < 0.05).
      High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics
      and serial levels of both parameters were lower than those treated with the
      combined regimen, although these were not statistically significant. Unlike the
      untreated venom activated whole blood, there was no clot formation following
      treatment with either the combined regimen or high dose AT-III. The results of
      this study suggested that the effect of Russell's viper venom on the clotting
      cascade is more potent and direct than that on platelet activity. There were
      complementary effects between antivenom and AT-III is controlling of both FPA and
      PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT
      III alone when administered in a sufficient dose, abolished the procoagulant
      effects of Russell's viper venom.

PMID- 8525403
TI  - Glomerulonephritis in Kelantan, Malaysia: a review of the histological pattern.
AB  - Renal biopsy is essential in the management of renal parenchymal diseases. Thus
      far there is no publish report on the pattern of glomerulonephritis in Kelantan.
      We decided to establish the pattern of glomerulonephritis in Kelantan and use
      this information as our reference in future studies. Records of patients who had
      proven glomerulonephritis histologically were analysed. Their biological data,
      clinical presentation, etiology and clinicopathological pattern were studied.
      Where appropriate mean and standard deviation were calculated. A total of 74
      biopsies were performed during the study period (between January 1991 and
      December 1993), out of which 72 biopsies (97.3%) were considered suitable for
      analysis. The male to female ratio was 1:1.1. Mean age at presentation was 27.6
      +/- 12.2 years. Nephrotic syndrome was the commonest clinical presentation
      (65.3%). The main underlying cause was systemic lupus erythematosus (50%)
      followed by primary glomerulonephritis. Histologically, IgA nephropathy and
      minimal change disease were the main patterns among patients with primary
      glomerulonephritis while diffuse proliferative glomerulonephritis was the
      commonest pattern among patients with lupus nephritis. Hence the pattern of
      glomerulonephritis is similar to other reported series. The procedure is
      considered safe and has a high success rate.

PMID- 8525404
TI  - Integration of control measures for malaria vectors in endemic areas of Thailand.
AB  - Various vector control measures were applied in different endemic areas in two
      provinces, Saraburi and Chanthaburi, with comparison among different control
      measures. Application of IGR (insect growth regurator, pyriproxyfen) was
      introduced at Wat Tam Pra Pothisat, Tab-Kwang District, Saraburi Province. Some
      integration measures were performed at villages 6 and 8, Patavee, Makham
      District, Chanthaburi Province. In Tab-Kwang District with low malaria endemicity
      at the study site predators were not able to be released due to rapid velocity of
      running water. IGR could effectively control malaria compared to the basin
      released predators. Another endemic areas villagers 6 and 8, Patavee, Makham,
      Chanthaburi Province was chosen. Highly endemic multidrug resistant malaria has
      been prevalent for many years in this area. Integration of Kanda's trapping
      system, application of IGR, use of both residual spraying and impregnated bed-net
      methods with etofenprox successfully interrupted malaria infection. The
      application of these methods as an integrated control system could be adjusted to
      environmental conditions. The results of this study suggest rapid effective
      vector control.

PMID- 8525405
TI  - Glutathion S-transferase activity and DDT-susceptibility of Malaysian mosquitos.
AB  - Comparative DDT-susceptibility status and glutathion s-transferase (GST) activity
      of Malaysian Anopheles maculatus, Culex quinquefasciatus and Aedes aegypti was
      investigated to ascertain the role of this enzyme in DDT resistance. The
      standardised WHO dose-mortality bioassay tests were used to determine DDT
      susceptibility in these mosquitos, whilst GST microassay (Brogdon and Barber,
      1990) was conducted to measure the activity of this enzyme in mosquito
      homogenate. It appeared that DDT susceptibility status of Malaysian mosquitos was
      not correlated with GST activity.

PMID- 8525406
TI  - Field observations on the swarming behavior of Armigeres subalbatus (COQ)
      (Diptera : Culicidae).
AB  - Swarming behavior of Armigeres subalbatus was observed in Pondicherry, South
      India. Swarming occurred both at dawn and dusk over stationary markers. The
      duration of swarming was longer at dust (135 minutes) and shorter at dawn (75
      minutes). Higher intensity in terms of relative density of participating males
      was observed at dusk when compared to dawn. Peak swarming activity was observed
      at light intensity ranging between 10 and 183 lux. Response to low light
      intensity of 1-10 lux was different during dawn and dusk. At this intensity
      initiation took place at dawn and termination was seen at dusk. Mating pairs were
      seen in the swarm. Analysis of the composition of swarms showed a male to female
      ratio of 1:0.01 at dusk and 1:0.02 at dawn. Besides nulliparous females, a few
      one parous and two parous females were also obtained from the swarm.

PMID- 8525407
TI  - Urban malaria and its vectors Anopheles stephensi and Anopheles culicifacies
      (Diptera : Culicidae) in Gurgaon, India.
AB  - The seasonal variation in the density of immature and adult malaria vectors
      Anopheles stephensi and An. culicifacies were recorded from January to December,
      1986 in urban Gurgaon, India. The highest combined anopheline larval density (2.3
      per dip) was recorded in the 31st week. The peak adult density for malaria
      vectors An. stephensi (4.14 per man hour) and An. culicifacies (1.02 per man
      hour) were reported in the month of August. The highest percentage of total
      infestation for anophelines and other breeding habitats were in tanks (48.72%)
      and ponds (6.41%) in Autumn and wells (4.79%) in the Winter season. The highest
      population of An. stephensi and An. culicifacies were collected from the
      peripheral area in comparison to central part of the study area. Maximum malaria
      cases along with highest larval density (1.8 per dip) were recorded from Sector
      3.

PMID- 8525408
TI  - Biting cycles of some potential vector mosquitos of Japanese encephalitis of
      Assam, India.
AB  - Biting activities of five potential vector species of Japanese encephalitis (JE)
      were observed in a JE affected district of Assam, India. Most of the species
      exhibited two peak periods of biting activity, one in early hours and other
      around midnight. However, in case of Culex fuscocephala several peaks were
      observed throughout the night.

PMID- 8525409
TI  - Field studies on the mosquito repellent action of neem oil.
AB  - Repellent action of neem oil was evaluated against different mosquito species. 2%
      neem oil mixed in coconut oil provided 96-100% protection from anophelines, 85%
      from Aedes, 37.5% from Armigeres whereas it showed wide range of efficacy from 61
      94% against Culex spp. Therefore, neem oil can be applied as a personal
      protection measure against mosquito bites.

PMID- 8525410
TI  - Effect of inorganic salts, soaps and detergents on dissolution and larvicidal
      activity of alginate formulation of Bacillus sphaericus.
AB  - Various inorganic salts and commonly used soaps and detergents were tested in the
      laboratory for their effect on the dissolution and larvicidal residual activity
      of a slow-release alginate encapsulated granular formation of Bacillus
      sphaericus. Fluoride, chloride and sulphate salts and a detergent powder affected
      the residual activity of this formulation drastically by rupturing it but did not
      effect its larvicidal activity. Nitrates and phosphates of sodium and potassium
      also had the same effect but to a moderate level. The safest concentration of
      these water impurities for effective functioning of the alginate encapsulated B.
      sphaericus formulation have been determined.

PMID- 8525411
TI  - Vaginal scrub prophylaxis in abdominal hysterectomy.
AB  - This study was aimed at reducing postoperative infection after abdominal
      hysterectomy in Chon Buri Hospital. Thirty patients scheduled for total abdominal
      hysterectomy were randomly divided equally into two groups of 15 patients each
      and received different preoperative preparation procedures. Group I patients
      received the procedure routinely used at Chon Buri Hospital comprising vaginal
      scrubbing in the evening before the operation day followed by abdominal scrubbing
      in operating room, whereas group II patients received the same treatment as Group
      I with additional vaginal scrubbing with 10% povidone-iodine immediately prior to
      the operation. All patients were given routinely antibiotics prophylaxis. After
      removal of the uterus, the discharge from the vaginal cuff was taken before and
      after closing the vaginal stump for aerobic and anaerobic cultures. Only 3 of
      group II patients (20%) were culture-positive before closure of vaginal cuff
      compared with 11 (73%) of group I patients (p < 0.01). After closure of the
      vaginal cuff, the positive bacterial culture declined to 5 (33%) in group I and 2
      (13%) in group II (p > 0.05). Most of isolated organisms were vaginal normal
      flora. Postoperative infection with E. coli occurred in 2 patients of group I and
      none of group II (p > 0.05). Our results suggested that additional prophylactic
      vaginal scrubbing reduced postoperative bacterial infections, but this observed
      reduction did not reach a statistically significant level. Thus a larger sample
      size is needed to substantiate whether vaginal scrubbing could be advocated in a
      routine practice.

PMID- 8525412
TI  - Anti-hepatitis A antibody titers after passive immunization with hepatitis A
      hyperimmune globulin.

PMID- 8525413
TI  - Salmonella: a rare cause of meningitis in an adult.

PMID- 8525414
TI  - Localized permanent epidemics: the genesis of chloroquine resistance in
      Plasmodium falciparum.
AB  - Localized permanent epidemics occur when, for an indefinite period of time, there
      is a temporary but continuous introduction of unprotected non-immunes into the
      same locality of a hyperendemic area. The main epidemiological factors involved
      in the genesis of localized permanent epidemics were encountered in Pailin
      (Cambodia) the epicenter of drug resistance in Southeast Asia: a very efficient
      vector, Anopheles dirus, exophilic and of limited distribution with, therefore,
      adjacent hyperendemic and non-endemic areas; a permanent pole of attraction in
      the hyperendemic area: Pailin's sapphires and rubies; a temporary but continuous
      influx of non-immunes into the pole of attraction: continuous influx of non
      immunes into the Pailin gem mining area. In the gem-mining Pailin village drug
      pressure was considerable: mass drug administration, a medicated salt project and
      permanent self-medication with very high doses, much higher doses being required
      to cure non-immunes with heavy infections and severe clinical attacks in epidemic
      situations. It appears, therefore, that the emergence of chloroquine resistance
      in Southeast Asia was the consequence of the localized permanent epidemics in
      Pailin. High level resistance was the result of continuous and intensive serial
      passages of P. falciparum in the non-immune subjects, large numbers of parasites
      being exposed to a high level of drug pressure at each passage. Similar
      epidemiological conditions are encountered in some parts of South America where
      the exophilic vector is An. nuneztovari. In Colombia, whose eastern mountains
      bordering Venezuela yield the most highly prized emeralds in the world,
      chloroquine resistance was detected at about the same time as in Southeast
      Asia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525415
TI  - Primary health care: the basis for malaria control in Hubei, China.
AB  - By 1992 malaria morbidity in Hubei, China had decreased steadily to its lowest
      level since 1970. Much of this achievement was through an integration of the
      primary health services with malaria control activities. However, in some areas
      malaria has been unstable due to weaknesses in the three tier health network.
      This has particularly been at the township and village level. The future of
      village doctors and appropriate measures of malaria control at the village levels
      are threatened by the change to a market economy. As part of the provincial
      health program, primary care services need to be improved in service provision,
      service organization and service quality.

PMID- 8525416
TI  - Malaria in prehistoric southeastern Asia.
AB  - This paper reviews the evolutionary and natural history of malarias; it is
      proposed that all human malarial parasites originated from zoonotic simian
      plasmodiids in tropical forests of southeastern Asia, during the terminal
      Pleistocene or early Holocene. The modes of malarial transmission among
      prehistoric natives of that geographic area is reconstructed, based primarily on
      ecological, archeological and ethnographic evidence. Early Holocene hunters and
      food gatherers of southeastern Asia shared the same forest habitats as several
      mosquito members of the Anopheles leucosphyrus group, known to be efficient
      malarial vectors. These forest dwellers could have maintained endemic malaria,
      however at low levels due to their low population density. With the abundance and
      interactive roles in transmitting human malaria of the An. dirus and An. minimus
      mosquitos in forest fringe areas, the middle Holocene settled farmers occupying
      such habitats would have been subject all year round to highly endemic malaria.
      Generally much lower and less uniform transmission of the disease could have been
      found among early coastal occupants, in the presence of the less efficient An.
      sundaicus vector. Malaria was practically absent on lowland floodplains,
      extensively occupied by human populations since the first millennium BC onwards,
      due to lack of major vectors.

PMID- 8525417
TI  - Electroencephalography in cerebral malaria.
AB  - Electroencephalography (EEG) was performed in 13 male patients with cerebral
      malaria during the first 24 hours of admission, using a 10-channel, 10-20 system
      EEG machine (6 montages, 20 minute duration). The EEG patterns were of theta and
      delta waves from both sides of cerebral hemisphere suggesting diffused cortical
      dysfunction. No epileptic pattern was found in patients who had seizures prior
      to, or after admission. The initial EEG performed on the day of admission did not
      show any specific pattern attributable to any pathological condition. It was also
      unable to predict the prognosis of the 2 dead patients. However, one cerebral
      malaria patient with left hemiplegia was subsequently found to have right basal
      ganglia hemorrhage in CAT scan, high amplitude delta waves and theta waves in the
      tracings of the right hemisphere. The study suggests that a single EEG data on
      admission can hardly give enough information for prediction of the clinical
      course and outcome of cerebral malaria. Serial EEGs probably provide more useful
      information regarding the prognostic signs in this group of patients.
      Nevertheless, EEG could be useful to rule out some cerebral pathology such as
      space occupying lesions, epilepsy or any other causes of unconsciousness that
      could produce similar cerebral symptoms in malaria patients.

PMID- 8525418
TI  - Comparison between microscopic examination, ELISA and quantitative buffy coat
      analysis in the diagnosis of falciparum malaria in an endemic population.
AB  - Monoclonal antibody-based ELISA and QBC (quantitative buffy coat analysis) were
      tested in two endemic areas with low and high incidence of malaria in
      Kanchanaburi Province, West Thailand with annual parasite incidence in 1992 of
      119 and 5 per 1,000 population, respectively. The numbers of individuals positive
      by thick blood film examination (TBF) for P. falciparum with or without P. vivax,
      and P. vivax only were 82 and 69, respectively. The detection limit of ELISA was
      10 parasites/10(6) red blood cells (RBC) (0.001% parasitemia). Of 1,095
      individuals involved in the study at the beginning of the study, ELISA showed
      sensitivity, specificity, positive predictive value and negative predictive value
      of 78.1%, 94.9%, 72% and 98.1%, respectively. Nine of 18 (50%) TBF-positive but
      ELISA-positive individuals had parasitemia of less than 10 parasites/10(6) RBC.
      High and low incidence areas did not affect the validity of our result.
      Regression analysis showed good correlation between log parasitemia and ELISA
      percent OD increase (Y = 0 + 64.9*logX, r = 0.65), and agreement between TBF and
      ELISA results was 95.9%. In a fortnightly follow-up, in 82 TBF-positive
      individuals, both ELISA and TBF positive rates correlatively declined with
      agreement of 96.3%. With samples taken on the first day of the study, the TBF and
      QBC results were also correlated with agreement of 95.8% for P. falciparum, 95.6%
      for P. vivax. During 8 week follow-up involving altogether 191 samples, agreement
      between TBF and QBC results were 87.4% for P. falciparum. QBC detected more cases
      with P. falciparum infections but detected smaller number of cases with P. vivax
      infections.

PMID- 8525419
TI  - Serum transcobalamin II levels in patients with malaria infection.
AB  - Serum transcobalamin II (TCII) levels were determined in 56 patients with P.
      falciparum malaria infection. They were divided into 3 groups: severe (malarial
      parasite > 5% or patients with cerebral malaria or renal insufficiency), moderate
      (1-5% infection without complications) and mild (1% infection). Elevated serum
      TCII values were found only in patients with severe malaria infection. These
      values correlated directly with parasitemia, blood urea nitrogen and creatinine,
      but were not correlated with alkaline phosphatase. As 17 patients with azotemia
      had elevated serum TCII levels while other 3 patients with normal BUN and
      creatinine concentrations had serum TCII levels within the normal limits. These
      findings indicated that malarial patients with renal insufficiency had increased
      serum TCII. A possible mechanism is the reduced TCII-B12 that filtered through
      the glomeruli due to the reduced renal blood flow with the decreased its uptake
      by proximal tubular cells resulting in the decreased degradation of TCII by the
      tubular lysosomal enzymes. Determination of serum TCII level may be used as an
      indicator of renal function in malarial patients with renal insufficiency.

PMID- 8525420
TI  - An evaluation of knowledge and awareness of disinfection and sterilization among
      health care workers.
AB  - Awareness of the disinfection and sterilization policy among hospital staff and
      their knowledge in basic principles and methods of disinfection and sterilization
      were studied before and after intervention using a self-administered
      questionnaire. Survey results showed that awareness (56.2%) before intervention
      was unsatisfactory. The nurses were more aware of the policy than other groups of
      medical personnel. Those unaware of the policy perform duties from memory or
      verbal instructions. A significant increase in awareness to 73.3% was observed
      after intervention (p < 0.05). Knowledge on methods of decontamination,
      disinfection and sterilization of equipment varies widely from 28.8% to 90.1%.
      23.1% were unaware of the temperature used for sterilization while 72.4% did not
      know how containers of disinfectant should be refill. Only 14.7% knew the
      recommended method for washing containers. With education improvement was
      observed. The average knowledge improved from 44.4% to 57.3%. Our results
      indicated that continuous in-service education is needed to improve, supplement
      and update knowledge in this field after basic training. In addition orientation
      programs for new staff should also be aimed at creating awareness and providing
      information on guidelines and policies related to their duties.

PMID- 8525421
TI  - The severity of disease measurements among Thai medical intensive care unit
      patients.
AB  - Since the diversity of diseases and complexities of treatment keeps on
      increasing, a precision of evaluation system that shows a strong and stable
      relationship to outcomes is needed. The APACHE II severity of disease
      classification system is an example that proved to be valid for large numbers of
      patients in different countries. Data from 334 Thai medical ICU patients were
      collected prospectively in order to validate the APACHE II system, and compare
      the findings with previous reports. Despite some differences in disease
      categories, the results showed close relation between APACHE II scores and the
      hospital mortality rate. The predictive power for death was strong with a
      specificity of 95% and correct prediction of 83% at the risk level of 0.5. The
      actual to predicted death ratio, an indicator of hospital performance, in this
      studied group was 1.17 and was close to the findings of most centers in USA. By
      providing a measure of severity of disease, APACHE II classification system can
      provide Thai researchers with a useful tool for clinical researches and improving
      the treatment of critically ill patients.

PMID- 8525422
TI  - Scoring systems for predicting outcomes of critically ill patients in
      northeastern Thailand.
AB  - The Acute Physiology and Chronic Health Evaluation System (APACHE) III, the
      APACHE II, the Simplified Acute Physiology Score (SAPS), and the Therapeutic
      Intervention Scoring System (TISS), calculated within the first 24 hours of
      admission, were compared in 209 critically ill patients admitted to the regional
      hospital in northeastern Thailand. Eighty-five (40.7%) patients subsequently
      died. The nonsurvivors had significantly higher APACHE III, APACHE II, SAPS and
      TISS scores than the survivors. ROC curves drawn for each severity index were in
      a discriminating position. There were no significant differences either among the
      areas under the ROC curves drawn for APACHE III, APACHE II, SAPS, and TISS, or
      among the overall accuracies of these indices. All four scoring system correlated
      well with the short-term prognosis, ie the mortality outcome, of critically ill
      patients. APACHE III, APACHE II, SAPS, and TISS appeared to be comparable to
      predictors of severity of critical illness. Selection of a severity indicator
      will depend on the resources available.

PMID- 8525423
TI  - Breast feeding behavior and supplementary food pattern of villagers in Udon Thani
      Province, northeast Thailand.
AB  - Breast feeding and supplementary food patterns were studied in 3 villages, of
      Udon Thani Province in Northeast Thailand. All children of 58 mothers were breast
      fed. Moreover, 42 mothers (72.4%), advised by health workers, fed their children
      with colostrum. Those who did not give colostrum believed that colostrum may
      cause diarrhea. Fifty-one (87.9%) children were fed Kaw Yam, northeast native
      food made out of baked chewed banana and sticky rice, within 1-7 days after
      birth. The mothers believed that the food will fill the child's stomach, and
      consequently, her baby will stop to cry. Powder milk was also given to the child
      as supplementary food. A powder milk had a high social value for the mother and
      also health worker advised them to feed the children with it. Rice porridge was
      additionally supplemented at the age of 6-8 months until weaning or, at the time
      when the child had two front teeth. Child's weaning was forced by applying the
      nipples with local bitter tasting herb. This study indicates that any health
      education within a community should be aware of traditional belief and customs of
      the population. The promotion of proper breast feeding, and the introduction of
      supplementary food to children should be consider traditional beliefs and combine
      it with health educational means, which will result in a better adoptability of
      the villagers to the promotion of adequate infant feeding.

PMID- 8525424
TI  - An unusual outbreak of food poisoning.
AB  - On August 25 1990, over 400 people who attended a Thailand handicappeds' sport
      day at a provincial physical education college developed gastrointestinal
      symptoms after having dinner. An epidemiological team want to determine causes(s)
      and recommend how to prevent and control a food poisoning outbreak. The
      investigation included interviewing all 1,210 persons who attended the sport's
      day. In addition, an environmental survey, laboratory analysis of food samples,
      and rectal, ear, throat and nasal swabs from foodhandlers were also performed. A
      case was defined as a person who ate any items of dinner food and experienced
      vomiting, nausea, abdominal pain, and diarrhea. There were 485 cases out of 1,094
      persons, an attack rate of 43%. Interviews were completed for 470 out of 485
      cases. The three most common symptoms were nausea (93%), vomiting (88%), and
      abdominal pain (81.5). The mean incubation period was 3.20 hours. Three out of
      four items of food had a significant association with illness. Among these 3
      items, eclairs had to the highest crude relative risk, 7.0 (95% CI = 4.8, 10.2).
      For statistical analysis, logistic regression by unconditional method was used,
      and found that only eclairs which were prepared during the night before the
      dinner and kept at room temperature for at least 12 hours before serving,
      remained statistically significant in the model (RR = 11.96; 95% CI = 9-22).
      Laboratory examination of foods and foodhandlers indicated heavy growth of
      Staphylococcus aureus producing toxins A and C and Bacillus cereus in eclairs.
      Culture of nasal swabs from healthy foodhandlers identified B. cereus and S.
      aureus of different phage types from those in eclairs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8525425
TI  - Antimicrobial therapy in Plesiomonas shigelloides-associated diarrhea in Thai
      children.
AB  - A retrospective case-controlled study was performed in 36 Thai children with
      Plesiomonas shigelloides (P. shigelloides)-associated diarrhea admitted to the
      Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol
      University from August 1990 to December 1992. Nineteen cases received antibiotics
      while seventeen did not receive any. The two groups were comparable in age, sex,
      duration of fever, duration and severity of diarrhea and medical treatment. The
      antibiotics given were norfloxacin, wintomylon, colistin, gentamicin,
      ceftriaxone, co-trimoxazole and ampicillin. In our study, 100% of P. shigelloides
      isolates were susceptible to quinolones and cephalosporins, while only 9% were
      susceptible to ampicillin. Co-trimoxazole, gentamicin, netilmicin,
      chloramphenicol and nalidixic acid showed high susceptibility. The duration of
      fever and diarrhea after treatment was not significantly different between
      treatment and control groups (p > 0.05). Therefore, we conclude that antibiotics
      did not change the duration of fever and diarrhea in Thai children with P.
      shigelloides-associated diarrhea.

PMID- 8525426
TI  - Comparative evaluation of bioassay and ELISA for detection of Japanese
      encephalitis virus in field collected mosquitos.
AB  - Comparative evaluation of enzyme-linked immunosorbent assay (ELISA) and bioassay
      (virus isolation in Toxorhynchites splendens larvae and identification by
      immunofluorescence test using virus specific monoclonal antibody) was carried out
      in order to define a suitable strategy for monitoring Japanese encephalitis virus
      infection in field mosquitos. A total of 8,850 adult female mosquitos in 177
      pools (Culex tritaeniorhynchus 91, Cx. vishnui 59 and Cx. fuscocephala 27)
      collected from an endemic area of Tamil Nadu were examined by both the
      techniques. In ELISA, 9 pools which had optical densities (OD) equal to the mean
      of normal infected pools plus > or = 4 standard deviations (SD) mean considered
      positive and all of them were virus positive by the bioassay also. Sixty-five
      pools had OD = Mean + 2-3 SD and 103 pools had OD = Mean + < 2 SD of normal
      pools. From these groups, 12 (18.5%) and 8 (7.8%) pools respectively were found
      to be virus positive by the bioassay. In total 29 (16%) pools were positive by
      the bioassay as against 9 (5%) by ELISA. This study demonstrated that the
      bioassay is sensitive for estimation of true positives and ELISA is a rapid
      screening system. A protocol has now been developed for surveillance in which
      field pools are first screened by ELISA and only those with OD = Mean + > or 2 SD
      are assayed in Toxorhynchites. By excluding a large majority of pools with low OD
      (Mean + < 2 SD), which are likely to yield to only a small percentage of true
      positives, the cost, time and labor involved are greatly reduced.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8525427
TI  - Epidemiologic characteristics of blood donors with antibody to human
      immunodeficiency virus: Thailand.
AB  - Of 782,190 volunteer blood donors in Bangkok and nearby areas, who were screened
      for infection with human immunodeficiency type 1 (HIV-1) from January 1988
      through December 1992, 3,219 tested positive on both enzyme immuno assay and
      Western blot assay. The identification variables of the donor were collected. The
      majority of HIV seropositive blood donors were male. The average age (median) of
      HIV seropositive was 26-29 years all through 1988-2992. The prevalence of HIV
      seropositive in male donors was higher than that in females. HIV seropositivity
      was confirmed in blood donations from first-time male donors in this study during
      1988-1992. This rate has increased progressively from 0.87/1,000 in 1988 to
      15.95/1,000 in 1992 with much higher rates in repeat donors. The repeat male
      donors increased from 0.77/1,000 in 1988 to 5.26/1,000 in 1991 and since then
      showed a decreased rate to 3.93/1,000 in 1992. Female donors were infected with
      HIV more frequently with the prevalence by sex ratio M:F rising from 27:1 in 1988
      to 6.6:1 in 1992. Comparing the seropositive rate between first time and repeat
      female donors, the results showed an increase in rate from 0.11/1,000 in 1990 to
      2.02/1,000 in 1992, but essentially the same rate in report donors. A majority of
      HIV seropositive blood donors (1990-1992) lived in Bangkok (42-49%) and among
      those who lived in one eastern province (Samut Prakan), 90-93% lived in the
      industrial areas. Of those who lived in Chon Buri Province, 73-88% lived in
      Sattaheep District, which is a naval base.

PMID- 8525428
TI  - Gene targeting in mouse embryonic stem cells with an adenoviral vector.
AB  - We examined the ability of an E1, E3-defective adenoviral vector to act as a
      substrate for homologous recombination with chromosomal DNA by including host
      chromosomal sequence from the mouse Fgr locus that also contained a selectable
      marker. After infection of mouse embryonic stem cells, stable integration was
      selected for neomycin resistance and the efficiency of homologous recombination
      was evaluated. The adenoviral vector was capable of infecting mouse embryonic
      stem cells efficiently. Between 30-50% of the input virus reached the nuclei
      after 24 hours of infection. Surprisingly, even without negative selection, 25
      40% of the integration resulted from homologous recombination at m.o.i. 10 and
      100, although the absolute efficiency of integration was low. Our results suggest
      that it is possible to modify the structure of an adenoviral vector to achieve a
      high gene targeting efficiency, resulting in regulated and long-term expression
      of an introduced gene.

PMID- 8525429
TI  - Tetracycline-regulated gene expression following direct gene transfer into mouse
      skeletal muscle.
AB  - For most experimental and therapeutic applications of gene transfer, regulation
      of the timing and level of gene expression is preferable to constitutive gene
      expression. Among the systems that have been developed for pharmacologically
      controlled gene expression in mammalian cells, the bacterial tetracycline (tet)
      responsive system has the advantage that it is dependent on a drug (tet) that is
      both highly specific and non-toxic. The tet-responsive system has been previously
      used to modulate expression of cell cycle regulatory proteins in cultured cells,
      reporter genes in plants and transgenic mice and reporter genes directly injected
      into the heart. Here we show that orally or parenterally administered tet
      regulates expression of tet-responsive plasmids injected directly into mouse
      skeletal muscle. Reporter gene expression was suppressed by two orders of
      magnitude in the presence of tet, and that suppression was reversed when tet was
      withdrawn. These data show that skeletal muscle offers an accessible and well
      characterized target tissue for tet-controlled expression of genes in vivo,
      suggesting applications to developmental studies and gene therapy.

PMID- 8525430
TI  - Mitotic and post mitotic consequences of genomic instability induced by oncogenic
      Ha-ras.
AB  - Induced expression of a mutant human Ha-ras oncogene in NIH3T3 cells leads to the
      rapid production of multicentric chromosomes, acentric chromosome fragments,
      double minute chromosomes, increased heteroploidy, and increased capacity to
      undergo gene amplification. In this study we have used fluorescent-in-situ
      hybridization (FISH) to demonstrate that induction of the Ha-ras oncogene also
      leads to disruption of the mitotic machinery, resulting in aberrant mitoses and
      abnormal daughter cells. Cells induced to express an oncogenic Ha-ras transgene
      accumulate chromosomes that lag outside of the rest of the chromosomal
      architecture, chromosomes that form bridges between daughter nuclei at anaphase,
      and that form micronuclei. Many of these mitotic aberrations contain structurally
      abnormal chromosomes. These ras-induced changes were suppressed by the
      introduction of a gene encoding the dominant negative effector of ras, raf 301.
      Expression of raf301 in cells induced to express Ha-ras reduced the level of
      growth in soft agar, chromosome aberrations, mitotic aberrations, and frequency
      of gene amplification. These data provide evidence for an association between Ha
      ras induced transformation, chromosome aberrations and gene amplification.
      Furthermore they offer insight into how the cell responds to the formation of
      aberrant chromosomes, and how disrupting chromosomal architecture could lead to
      further imbalances in the distribution of genetic material between daughter
      cells.

PMID- 8525431
TI  - Molecular cloning of the human gene SUVCC3 associated with the formation of DNA
      protein crosslinks following exposure to solar UV radiation.
AB  - DRP 153 cells, which are hypersensitive to solar UV and deficient in the
      formation of DNA-protein crosslinks (DPC) following irradiation, were transfected
      with human DNA and a secondary transformant obtained in which a normal DPC
      response and solar UV sensitivity reestablished. DNA from this secondary
      transformant was used to construct a genomic DNA library from which a recombinant
      phage was isolated containing the human gene capable of restoring a normal DPC
      response and solar UV sensitivity to DRP 153. This gene has been designated
      SUVCC3 to denote solar UV cross-complementing gene number 3.

PMID- 8525432
TI  - Persistent expression of genes transferred in the fetal rat liver via
      retroviruses.
AB  - The transfer of genes into the fetal liver is a promising approach for correction
      of inborn errors in metabolism identified in prenatal life. In this study, we
      demonstrate that gene transfer to the fetal rat liver resulted in the stable
      expression of the gene in the hepatocytes of the adult animals. This was achieved
      by a combination of gene transfer via ecotropic retroviruses in the fetal liver
      with subsequent partial hepatectomy of the offspring. Replication incompetent,
      ecotropic and amphotropic retroviruses were used to transfer the bovine growth
      hormone gene (bGH) linked to the promoter (-450 to +73) for the P-enolpyruvate
      carboxykinase (PEPCK) gene into the fetal liver in the last trimester of
      gestation. Amphotropic retroviruses were unable to infect the fetal liver due to
      the lack of expression of their receptors. The fetal liver was infected by the
      ecotropic retroviruses and partial hepatectomy of the offspring at one month of
      age stimulated expression of the PEPCK/bGH gene in the liver over ten fold.
      Expression of the gene persisted for as long as one year. A heterogeneous pattern
      of expression of the chimeric gene throughout the liver parenchymal cells was
      identified with higher expression in the pericentral region of the liver. This
      zonation of expression was not expected, since the endogenous PEPCK gene is
      expressed in periportal hepatocytes. We suggest that, following partial
      hepatectomy DNA replication activates expression of the proviral PEPCK/bGH gene,
      mainly in midzonal and pericentral hepatocytes. Proviral sequences may influence
      the expression of the PEPCK/bGH gene in parenchymal cells in which the PEPCK
      promoter is not normally active.

PMID- 8525433
TI  - Characterization of cDNA clones containing CCA trinucleotide repeats derived from
      human brain.
AB  - Expansion mutation is the cause of eight neuropsychiatric disorders. Thus far
      each disease is the result of expansion of a C-G rich trinucleotide repeat that
      is polymorphic for length in the general population. We now report the
      identification of seven novel cDNA clones with CCA or equivalent trinucleotide
      repeats obtained by screening a human frontal cortex cDNA library. The repeat
      lengths of two clones, CCA11 (linked to D20S101, expressed in human brain as a
      3.2 kb message) and CCA38 (linked to D5S404), are highly polymorphic in a normal
      human population. CCA54, mapped to chromosome 19, appears to correspond to a
      portion of the human gene encoding the alpha 1 subunit of a P-type calcium
      channel. Expansion mutations at these loci should be considered as possible
      candidates in evaluating the genetic etiologies of diseases linked to chromosomes
      5, 19, and 20.

PMID- 8525434
TI  - Prevention of DNA 5-methylcytosine reutilization in human cells.
AB  - DNA methylation is an important process contributing to transcriptional
      regulation in animal and plant cells. The well known reutilization of DNA
      nucleotide bases indicated that DNA degradation occurs in many cells and tissues.
      On the other hand, the reutilization of 5-methyl-2'-deoxycytidine monophosphate
      in the DNA synthesis would have deleterious effects on gene regulation. Recent
      molecular insights into the exclusion of exogenous 5-methylcytosine from DNA are
      the subject of this review.

PMID- 8525435
TI  - Laparoscopic surgery for intestinal obstruction.
AB  - The indications for laparoscopic surgery have steadily diversified over the last
      several years. At the present time, the level of comfort with laparoscopic
      procedures has allowed surgeons to perform procedures which several years ago
      never would have been attempted. One of the indications for surgery which has
      only recently been appreciated is bowel obstruction. Specifically, in the last
      several years a number of authors have described successful application of the
      laparoscope to treat patients with either acute or chronic bowel obstruction.
      This article reviews the indications and contraindications for the procedure as
      well as recommended preoperative evaluation and suggested surgical technique.
      Furthermore, the early results in these few series is discussed.

PMID- 8525436
TI  - Laparoscopic Nissen-Rossetti fundoplication. First results.
AB  - From January 1992 to July 1994, 148 patients with symptomatic gastroesophageal
      reflux and/or hiatal hernia underwent Nissen-Rossetti fundoplication by a
      laparoscopic approach. There was no conversion and no postoperative death. The
      main intraoperative complications were hemorrhage (n = 12), pleural opening (n =
      5), and gastric perforation (seromuscular effraction) (n = 1). Laparoscopic
      reoperation was necessary in two patients as a result of bleeding, and there were
      two cases of food impaction. The median hospital stay was 4.9 days; 117 patients
      were observed for follow-up for 3-31 months (median 6.2 months). Eleven cases of
      dysphagia extending beyond 2 months have been observed. In five of those cases,
      endoscopic dilatation provided effective treatment of dysphagia and in four
      others, a further laparoscopic intervention enabled a cure to be obtained. Eighty
      four percent are satisfied with their decision to have the operation. The
      laparoscopic Nissen-Rossetti fundoplication can be carried out safely and
      effectively with positive results similar to those obtained with the open
      procedure and with all of the advantages of the minimally invasive approach.

PMID- 8525437
TI  - Complications of laparoscopic cholecystectomy in HIV and AIDS patients.
AB  - We retrospectively evaluated the results of laparoscopic cholecystectomy in
      patients infected with the human immunodeficiency virus (HIV) with and without
      acquired immunodeficiency syndrome (AIDS). One thousand one hundred twenty-seven
      consecutive patients underwent laparoscopic cholecystectomy by our surgical
      group. Eighteen of these patients were known to be infected with the HIV virus; 6
      were asymptomatic and 12 had AIDS. We reviewed the medical records of all HIV
      positive individuals with regard to morbidity, mortality, and postoperative
      outcome following laparoscopic cholecystectomy. In the six HIV-patients without
      AIDS, five (83%) had improvement of symptoms postoperatively. There was one minor
      complication (17%). In contrast, only one of the 12 patients with AIDS had
      postoperative improvement of symptoms and eight (66%) had complications after
      surgery. There were four deaths (33%) within 30 days of surgery in this group.
      Only a small percentage of AIDS patients benefit from laparoscopic
      cholecystectomy. There is a significantly morbidity and mortality following this
      procedure in this group. Strategies to improve outcome are presented.

PMID- 8525438
TI  - Laparoscopic surgery in the management of traumatic hemoperitoneum in stable
      patients.
AB  - Unnecessary laparotomies in patients with abdominal traumatism (AT) who present
      hemoperitoneum with stable hemodynamics may be avoided if a
      diagnostic/therapeutic laparoscopy is performed. Between July 1992 and December
      1994, 24 patients with AT and hemoperitoneum underwent this exploration: 5 were
      found to have a large retroperitoneal hematoma; 2, a tear in the intestinal
      mesenterium; 4, hepatic injuries; and 13, splenic lesions. Of the 24 patients, 9
      needed conversion to open exploration: 8 during the laparoscopy and 1 shortly
      after operation. Mean hospital stay was 7 days (5-9). There was no morbidity or
      mortality in the series. Diagnostic/therapeutic laparoscopy is a method that is
      efficient and economical and can easily be undertaken by surgeons with experience
      in laparoscopy; it may be a valid alternative to conservative treatment or
      laparotomy in AT and hemoperitoneum patients who are hemodynamically stable.

PMID- 8525439
TI  - Interleukin 6 (IL-6) levels in the monitoring of surgical trauma. A comparison of
      serum IL-6 concentrations in patients treated by cholecystectomy via laparotomy
      or laparoscopy.
AB  - Interleukin 6 (IL-6) is involved in the processes of inflammation and tissue
      repair. We have been looking for the correlation between IL-6 concentration in
      patient's serum and the other factors related to the gravity of surgical trauma.
      Out of 25 patients with acute cholecystitis, 11 were randomly selected for
      laparoscopic cholecystectomy and the other 14 for open (laparotomic)
      cholecystectomy. The diagnostic and prognostic factors, age, and duration of
      disease did not differ significantly in either group. IL-6 serum levels were
      monitored by using commercially available ELISA tests throughout 72 h following
      the surgery. In patients who underwent laparoscopy, average IL-6 serum levels
      were significantly (up to fourfold) lower than in their laparotomy-treated
      counterparts, and the monitoring of IL-6 serum levels seems to be useful in the
      evaluation of the extent of trauma caused by surgery.

PMID- 8525440
TI  - Current management of common bile duct stones in northern Italy.
AB  - In order to obtain a complete picture of the current management of
      cholecystocholedocal lithiasis in northern Italy we've conducted the present
      survey. In the years 1992-1993, among 7,861 cholecystectomies, 665 patients with
      gallbladder and common bile duct stones were treated in 49 surgical departments.
      Some 271 (43%) were treated by traditional methods: open surgery or endoscopic
      sphincterotomy followed by laparotomic cholecystectomy; 313 patients (49%) were
      treated by endoscopic sphincterotomy followed by laparoscopic cholecystectomy and
      only 38 (6%) were treated by one-stage laparoscopy, either by a transcystic
      approach (27) or by laparoscopic choledochotomy (11). Morbidity and mortality
      were not significantly different in the different groups. We conclude that open
      surgery and sequential minimal invasive treatment are the standard approaches to
      cholecystocholedochal lithiasis in this first stage of the laparoscopic era. The
      laparoscopic management of common bile duct stones is at present confined to
      surgical departments specially devoted to laparoscopic surgery.

PMID- 8525441
TI  - Laparoscopic cholecystectomy. Intraoperative findings and postoperative
      complications.
AB  - From November 1990 to April 1994 we attempted laparoscopic cholecystectomy (LC)
      in 1,788 consecutive patients. The intraoperative findings related to
      gallbladder's pathology were as following: chronic cholecystitis in 792 patients
      (44.3%), simple cholecystolithiasis in 760 (42.5%), acute cholecystitis in 98
      (5.5%), hydrops in 44 (2.5%), empyema in 38 (2.1%), gangrenous cholecystitis in
      12 patients, acalculous cholecystitis in 20 patients, polyps in 11 patients,
      adenomyomatosis in 9 patients, and gallbladder's carcinoma in 4 patients.
      Although we had a considerable number of cases with severe inflammation and/or
      dense adhesions the conversion rate to open surgery was relatively low (2.5%).
      There was no procedure-related mortality and no common bile duct injury.
      Postoperative complications occurred in 58 patients (3.2%). Bile leak was present
      in 19 patients, retained bile duct stones in 8, severe bleeding in 6, mild
      pancreatitis in 4, pulmonary embolism in 1, cerebral bleeding in 1, wound
      infection in 6, abdominal wall hematoma in 4, and umbilical incisional hernia in
      2; 7 patients presented other minor complications. The mean postoperative
      hospital stay of our patients was 1.8 days (range 1-12 days). Adequate measures
      to prevent intraoperative accidents, meticulous technique, and full maintenance
      of the equipment are among the most important factors in keeping a low conversion
      and complication rate in the patients undergoing LC.

PMID- 8525442
TI  - Experimental laparoscopic aortobifemoral bypass.
AB  - The goal of the present study is to develop a technique for laparoscopic
      aortobifemoral bypass. Piglets weighing between 60 and 78 kg were anesthetized
      with halothane. The lateral retroperitoneal approach was preferred to the more
      familiar anterior transperitoneal approach and was successfully completed in 19
      piglets. The piglets were placed in the right lateral decubitus position. The
      first port (2 cm) was inserted halfway between the tip of the 12th rib and the
      iliac crest. Four other trocars were placed in the retroperitoneum after balloon
      inflation had allowed creation of a space which permitted visualization of the
      aorta from the left renal artery down to the aorto-iliac junction. After
      evacuation of the retropneumoperitoneum, the cavity was maintained using an
      abdominal lift device and a retractor. Using this approach, we performed four
      aorto-bifemoral bypasses (end-to-end aortic anastomosis) after conventional
      intravenous heparinization (100 IU/kg) in less than 4 h. Blood loss did not
      exceed 250 ml and the hematocrit remained stable. Postmortem evaluation of the
      grafts revealed they were positioned as in a conventional bypass, their limbs
      having followed in the created retroperitoneal tunnels along the path of the
      native arteries. No mortality occurred before sacrifice of the animals. We
      believe that this first performed series of totally retroperitoneal laparoscopic
      aortobifemoral bypasses in the porcine model is useful in preparation for human
      application due to the anatomical similarities in the periaortic region.

PMID- 8525443
TI  - Effect of a pneumoperitoneum on the extent and severity of peritonitis induced by
      gastric ulcer perforation in the rat.
AB  - Laparoscopic surgical repair of perforated gastroduodenal ulcer is technically
      feasible. To study the effect of a pneumoperitoneum on the extent and severity of
      peritonitis this animal study was devised. In rats gastric ulceration was induced
      by instillation of ethanol (50%, 2 ml) and followed by gastrotomy to simulate
      perforation. Animals were randomly allocated to pneumoperitoneum (PP) and control
      groups. In PP groups CO2 was insufflated intraperitoneally 6, 9, 12, and 24 h
      after gastrotomy. In controls the abdomen was only punctured. Animals were
      sacrificed 5 h after the end of PP or abdominal puncture. Blood cultures and
      intraabdominal swabs were assessed. A peritonitis severity score (PSS) based on
      histologies from peritoneum, liver, left kidney, spleen, and first jejunal loop
      was estimated. Six and 9 h after gastrotomy no significant differences between
      the PP and control groups were observed; 12 h after gastrotomy cultures of blood
      samples and abdominal swabs were positive in 67% and 75% in the PP group compared
      to 42% (P < 0.05), and 42% (P < 0.05) in controls. The mean PSS was 20.8
      (standard deviation [SD] 2.2) in the PP group compared to 11.3 (1.5) (P < 0.01)
      in controls; 24 h after gastrotomy cultures of blood samples and abdominal swabs
      were positive in 83% and 100% in the PP group compared to 42% (P < 0.05) and 50%
      (P < 0.01) in controls. The mean PSS was 22.1 (1.5) in the PP group compared to
      11.8 (2.4) (P < 0.01) in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525444
TI  - Our experience with early integration of laparoscopic cholecystectomy in surgical
      residency training.
AB  - Laparoscopic cholecystectomy is now a method of choice in treating symptomatic
      cholelithiasis. The aim of this study was to assess an early integration of
      surgical residents into performing laparoscopic cholecystectomies and the
      significance of the integration for their training. Since February 1992
      laparoscopic cholecystectomy (LC) has been performed in our institutions. During
      the 1st year 253 LCs were done by 4 surgeons--2 residents (in postgraduate years
      3 and 4) and 2 staff surgeons; the 2nd year the team was extended and 301 LCs
      were performed. The residents operated on 364 cases (66%); the overall conversion
      rate was 5.4%; in the group of patients operated by residents (R) it was 3.8%; in
      the group operated by staff surgeons (SS) it was 8.4%. The complication rates did
      not exceed literature reports. The overall complication rate was 3.4%, in the "R"
      group 3.0% and in the "SS" group 4.2%. It may be concluded that surgical
      residents can perform LC without additional complications after initial
      experience with the open technique and appropriate hands-on laboratory training
      period before starting LC. Continuous training in advanced open biliary
      procedures should be assured for senior surgical residents.

PMID- 8525445
TI  - Laparoscopic-assisted abdominal aortic aneurysm repair.
AB  - Since the advent of laparoscopy, the sweeping changes seen in general surgery
      have not been paralleled in vascular surgery. There have been case reports of
      laparoscopic-assisted aortobifemoral bypass for occlusive disease. Because
      aneurysmal disease comprises the majority of aortic surgery, we pursued animal
      and cadaveric feasibility studies for laparoscopic-assisted abdominal aortic
      aneurysm (AAA) repair. We present a case report of the first clinical case
      performed under Institutional Review Board protocol using this technique. The
      patient was a 62-year-old male with a 6-cm infrarenal AAA. After obtaining a
      pneumoperitoneum, a modified fish retractor was used to exclude the bowel. Ten 11
      mm ports provided access to laparoscopically dissect the neck of the aneurysm and
      the iliac vessels. Then, a 10-cm minilaparotomy was performed and standard
      vascular clamps were inserted via the port incisions. Standard aneurysmorraphy
      was performed with a polytetrafluoroethylene (PTFE) tube graft. Laparoscopy
      conferred three major benefits: better visualization of the aneurysm neck, less
      bowel manipulation, and avoidance of hypothermia. This case report illustrates
      the feasibility of laparoscopic-assisted aneurysm repair. Controlled human
      studies will define the role of laparoscopy in AAA surgery.

PMID- 8525446
TI  - Cholecystectomy in the peritoneal dialysis patient. Unique advantages to the
      laparoscopic approach.
AB  - Laparoscopic cholecystectomy has proven to be a safe and effective treatment for
      symptomatic gallstone disease. Several subsets of patients, however, may not be
      candidates for the laparoscopic approach, including patients with morbid obesity,
      acute cholecystitis, and previous abdominal surgery. Because of peritoneal
      thickening and abdominal adhesions secondary to peritoneal dialysis, the
      applicability of laparoscopic cholecystectomy in patients maintained on chronic
      peritoneal dialysis is also unclear. We performed laparoscopic cholecystectomy on
      three peritoneal dialysis patients without intraoperative complications. We have
      noted several unique advantages to laparoscopic surgery in this patient
      population and advocate this approach in peritoneal dialysis patients requiring
      cholecystectomy.

PMID- 8525447
TI  - Acute cholecystitis with calculous biliary duct obstruction in the gravid
      patient. Management by ERCP, papillotomy, stone extraction, and laparoscopic
      cholecystectomy.
AB  - The pregnant patient with cholelithiasis is subject to the manifold complications
      associated with this disease. The management of a gravid patient with acute
      cholecystitis complicated by biliary duct obstruction utilizing combined
      endoscopic therapy and laparoscopic cholecystectomy is reported. The benefits to
      the patient and fetus when successful are apparent, but it is important to
      anticipate potential problems associated with laparoscopy in pregnancy and to
      avoid them. Various safeguards such as fetal monitoring, careful trocar
      placement, and intra-abdominal pressure monitoring have been suggested and should
      be appropriately utilized to enable a satisfactory outcome. Case reports such as
      this may further clarify the interdependent role of laparoscopic cholecystectomy
      and ERCP and their application to the pregnant patient.

PMID- 8525448
TI  - Laparoscopic resection of an adenoma of the urachus in combination with a
      laparoscopic cholecystectomy.
AB  - In a 40-year-old male patient with symptomatic cholecystolithiasis, ultrasound
      examination disclosed a large cystic mass on the dome of the bladder.
      Laparoscopic resection of this mass was carried out in combination with a
      laparoscopic cholecystectomy. Histology disclosed an urachal adenoma.
      Postoperative recovery was uneventful. We conclude that urachal adenomas can be
      managed safely by laparoscopic means.

PMID- 8525449
TI  - Thoracic herniation and intrathoracic gastric perforation after laparoscopic
      fundoplication.
AB  - This case report describes a serious complication after laparoscopic Rosetti
      fundoplication. Two days postoperatively the proximal part of the stomach
      herniated into the thoracic cavity where a gastric perforation caused leakage.
      The patient was reoperated and a new fundoplication was constructed.
      Postoperatively the patient recovered. Possible mechanisms are discussed.

PMID- 8525450
TI  - Bilateral adrenal hemorrhage following laparoscopic cholecystectomy.
AB  - Massive bilateral adrenal hemorrhage occurring in the postoperative period is an
      unusual but potentially life-threatening complication of any abdominal operation.
      The diagnosis is often difficult due to the nonspecific nature of the clinical
      presentation, which is easily attributable to other more common postoperative
      conditions. We report a case of bilateral adrenal hemorrhage resulting in acute
      primary adrenal insufficiency following an otherwise-uncomplicated laparoscopic
      cholecystectomy, which has not previously been described. An awareness of the
      possibility of this uncommon condition complicating laparoscopic cholecystectomy
      may lead to a higher index of suspicion, which is important in timely diagnosis
      and prompt treatment.

PMID- 8525451
TI  - Laparoscopic splenectomy. Technique and results in a series of 27 cases.
AB  - Between early 1992 and December 1994, laparoscopic splenectomy was performed in
      27 patients with idiopathic thrombocytopenia (ITP), hairy-cell leucemia, HIV, or
      Hodgkin's disease. In all cases medical treatment, especially cortisone therapy,
      failed. In Hodgkin's disease the splenectomy was combined with liver biopsies and
      dissection of parailiacal, paraaortic, and mesenteric lymph nodes for abdominal
      staging. The operation was performed using four trocars; the splenic vessels were
      divided by a linear stapler. In general the spleen was removed in a bag through a
      slightly enlarged trocar incision or after morcellation. Three patients needed a
      small laparotomy for the removal (laparoscopic assisted). In a recent case of
      Hodgkin's disease the intact spleen was removed via posterior colpotomy. In 22 of
      27 cases (81%) the operation was finished laparoscopically. Five times a
      conversion to conventional laparotomy was necessary because of bleeding of
      enlarged lymph nodes at the hilum. Wound infections occurred in two cases. In one
      patient with ITP the platelet count did not improve and continuous blood loss led
      to relaparotomy at the 1st postoperative day. No surgical bleeding was found. All
      patients tolerated a fluid diet at the 1st postoperative day and hospitalization
      time was 4.4 days (range 3-14). Regarding the low complication rate and the
      advantages of a smaller abdominal trauma in the postoperative period, the
      laparoscopic approach for elective splenectomy and laparoscopic abdominal staging
      has a substantial benefit for the patients.

PMID- 8525452
TI  - Evolving techniques in endoscopic extraperitoneal herniorrhaphy.
AB  - Endoscopic extraperitoneal herniorrhaphy (EEPH) was utilized to repair 326 groin
      hernias in 249 patients over a 32-month period. Nearly one in ten of the repairs
      was for a recurrent hernia. Several patients had contralateral hernias diagnosed
      only at the time of endoscopic examination. A recurrence rate of 1.6% and an
      overall complication rate of 5.2% are cited. After a plateau was reached on the
      surgeon's learning curve, various modifications in technique were implemented.
      Through these modifications, EEPH has become a safe, efficient, and standardized
      operation that can be performed with decreasing costs to the hospital and with
      increasing advantages to the patient.

PMID- 8525453
TI  - The sequelae of retained or lost stones. A complication of laparoscopic
      cholecystectomy.

PMID- 8525454
TI  - Laparoscopic management of common bile duct stones.

PMID- 8525455
TI  - The feasibility of safe laparoscopic treatment of hydatid cysts of the liver.

PMID- 8525456
TI  - Regulation and functional characterization of a rat recombinant dopamine D3
      receptor.
AB  - We stably expressed a rat D3 receptor cDNA in C6 glioma cells (C6-D3 cells),
      quantifying receptor expression with the radioligands [125I]epidepride (KD = 0.1
      nM) and [3H]spiperone (KD = 0.7 nM). As reported previously for D2 receptors,
      quinpirole induced a 9-16% increase in the rate of extracellular acidification by
      C6-D3 cells. The acidification was inhibited by epidepride and by the Na+/H+
      antiporter inhibitors, amiloride and methylisobutylamiloride, but pertussis toxin
      treatment had no effect on quinpirole-induced extracellular acidification. These
      data suggest that D3 receptor stimulation of Na+/H+ exchange in C6 glioma cells
      is not mediated by the pertussis toxin-sensitive G proteins, Gi or G(o).
      Overnight treatment of C6-D3 cells with N-propylnorapomorphine, dopamine, or
      quinpirole resulted in large concentration-dependent increases (up to 500%) in
      the density of D3 receptors on membranes prepared from the cells. Antagonists had
      smaller, variable effects on the density of D3 receptors in C6-D3 cells, except
      for domperidone, which significantly increased the density of D3 receptors.
      Treatment with pertussis toxin had no effect on the agonist-induced receptor up
      regulation, indicating that an interaction with pertussis toxin-sensitive G
      proteins was not required. Densitometry analysis of Northern blots of RNA
      prepared from C6-D3 cells showed no significant N-propylnorapomorphine-induced
      increase in D3 receptor message. Treatment with cycloheximide, however,
      completely prevented receptor up-regulation by N-propylnorapomorphine.
      Pretreatment of C6-D2 cells with 10 microM DA resulted in a substantial
      heterologous sensitization, in which isoproterenol-stimulated adenylyl cyclase
      activity was enhanced more than twofold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525457
TI  - The road to tranquility: the search for selective anti-anxiety agents.
AB  - The earliest treatments of anxiety included cathartics and emetics, which were
      used to remove the excess of black bile (hence our word melancholia) thought to
      be responsible for the patient's demeanor. By the 1700s, physicians were
      prescribing drugs that are more selective for the CNS, chiefly opium and
      strengthening tonics. In the 1860s, cardioactive drugs such as atropine, aconite,
      and digitalis were assumed to counteract anxiety because it could be associated
      with tachycardia and/or melancholia. A little later, the emergence of laboratory
      animal models, culminating in the conditioned avoidance response, and also
      Freudian psychiatry, permitted the evolution of new definitions of anxiety, as
      well as the introduction of sedative agents such as KBr, chloral hydrate, and
      barbiturates for its treatment. The first somewhat selective anxiolytics,
      reserpine, meprobamate, and chlorpromazine, appeared in the early 1950s, while in
      1959 the benzodiazepines were the first to prove more selective than all the
      others in a systematic battery of screening tests.

PMID- 8525458
TI  - In vivo-synthesized radioactively labelled alpha-methyl serotonin as a selective
      tracer for visualization of brain serotonin neurons.
AB  - To investigate the use of alpha-[3H]methyl tryptophan (alpha-[3H]MTrp) as a
      tracer for the in vivo study of brain serotonergic neurons, we examined whether
      alpha-[3H]MTrp and its metabolite alpha-[3H]methyl serotonin (alpha-[3H]M5-HT)
      selectively label serotonergic neurons and whether once accumulated in these
      neurons, the radioactive metabolite behaves like endogenous serotonin. Rats
      received a systemic injection of 1-5 mCi of alpha-[3H]MTrp and 24 h later their
      brains were immediately removed or fixed by perfusion before removal. Tissue
      sections in which serotonergic neurons had been immunostained for 5-HT or its
      synthesizing enzyme, tryptophan hydroxylase, were processed for radioautography
      at the light and electron microscopic level. In another group of rats, the
      release of radioactivity from different brain areas was studied both under basal
      and depolarizing conditions. In the dorsal raphe nucleus, the light microscopic
      examination revealed almost complete colocalization between serotonergic neurons
      and those that accumulated radioactivity, with a heterogeneity in the content of
      alpha-[3H]M5-HT among the various cells. At the ultrastructural level,
      immunoidentified serotonergic perikarya and dendritic processes in the dorsal
      raphe nucleus, as well as nerve terminals in the cerebral cortex were also found
      to contain alpha-[3H]M5-HT. Under basal conditions, radioactivity was released
      from the brainstem raphe region and from projection areas such as the striatum
      and hippocampus. The basal output of alpha-[3H]M5-HT increased approximately
      twofold after a depolarizing 50 mM KCl solution was added to the perfusion fluid.
      These findings suggest that newly synthesized alpha-[3H]M5-HT can be released
      both at somatodendritic and terminal sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525459
TI  - Time-course of modifications elicited by reserpine on the density and mRNA
      synthesis of the vesicular monoamine transporter, and on the density of the
      membrane dopamine uptake complex.
AB  - The long-term effects of a unique injection of reserpine (5 mg/kg s.c.) on the
      vesicular monoamine transporter and dopamine uptake complex have been
      investigated, in parallel with behavioral and neurochemical effects. Early after
      treatment, a dramatic decrease in locomotor activity, as well as a marked
      depletion in striatal dopamine (DA), associated with a prominent enhancement in
      dopaminergic turnover were observed in reserpine-treated rats. From 2 to 60 days
      after reserpine injection, a recovery in locomotor activity occurred, in parallel
      with an increased DA content in the striatum, reaching about 50% of controls at
      day 60. At this time, the dopamine turnover was quite normal. The density of the
      dopamine uptake sites in the striatum, studied with 3H GBR12783, was unchanged
      after reserpine treatment at any time studied up to 60 days. By contrast, the
      density of binding sites for 3H dihydrotetrabenazine (3H TBZOH), a marker for the
      vesicular monoamine transporter, remained dramatically decreased in the striatum
      all over the time of the study (> -90% of controls at day 2 and -80% at day 30
      and 60). A lesser decrease (-60%) was observed in the substantia nigra pars
      compacta (SNc), 2 and 30 days after reserpine treatment. This suggests that at
      least 60% of the vesicular monoamine transporter is sensitive to reserpine in
      this cell bodies region, indicating that this proportion of the transporter is
      integrated in functional vesicles, a prerequisite for reserpine binding.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8525460
TI  - Identification of age-related changes of dopamine D1-like receptors in the rat
      cerebellar cortex.
AB  - The present study was designed to characterize the pharmacological profile of
      dopamine D1-like receptors in the rat cerebellar cortex and to assess if these
      receptor sites undergo age-related changes. Cerebella of young (3 months), adult
      (12 months), and old (27 months) male Wistar rats were examined by using
      radioligand binding techniques and light microscope autoradiography. The non
      selective dopamine D1-like radioligand [3H]SCH 23390 was specifically bound to
      sections of rat cerebellum. The findings that dopamine displaced [3H]SCH 23390
      binding in the submicromolar range suggest that labelling of a dopamine D5 (or
      D1B) receptor subtype. The affinity of [3H]SCH 23390 for dopamine D1-like
      receptors was similar in the cerebellar cortex of the three animal groups
      investigated, whereas radioligand binding techniques revealed a gradual age
      related reduction of the density of binding sites. Light microscope
      autoradiography showed the localization of [3H]SCH 23390 binding sites primarily
      in the molecular layer and to a lesser extent in the Purkinje neuron layer of the
      cerebellar cortex. Aging was accompanied by a loss of [3H]SCH 23390 binding sites
      affecting mainly the molecular layer. The age-dependent loss of dopamine D1-like
      receptors is more pronounced if detected with radioligand binding techniques than
      with light microscope autoradiography. This suggests that the decrease of
      dopamine D1-like receptors observed in aging rat cerebellar cortex may depend in
      part on changes in the receptor expression and in part on cortico-cerebellar
      structural changes.

PMID- 8525461
TI  - Effect of L-dopa and 6-hydroxydopamine lesioning on [11C]raclopride binding in
      rat striatum, quantified using PET.
AB  - A positron emission tomograph (PET) was used to image D2 dopamine receptor
      function in rat striata and to obtain regional time-radioactivity curves from
      individual rat brains following i.v. injection of carbon-11-labelled raclopride.
      Despite the limited resolution of the camera, together with associated spillover
      and partial volume effects, the kinetic data obtained from striata were such that
      specific binding of the radioligand could be quantified unilaterally, using a
      reference tissue compartmental model, with cerebellum data as an indirect input
      function. With the exception that the rat is anaesthetised, the experimental
      system is analogous to the acquisition and collection of clinical PET data and,
      by using animal models of disease, can be used to aid the interpretation of
      clinical studies. Using 6-hydroxydopamine (6-OHDA) lesioning of the substantia
      nigra pars compacta to produce a rat hemiparkinsonian model, the present results
      confirm that deafferentation causes a supersensitivity of post-synaptic D2
      dopamine receptors. Saturation studies indicated that the measured 23% increase
      in [11C]raclopride binding potential reflected a change in receptor affinity.
      Modulation of extracellular dopamine concentration, monitored by in vivo
      microdialysis, demonstrated that the increased binding was unlikely to be due to
      a reduction in receptor occupancy by endogenous dopamine. Acute administration of
      L-3,4-dihydroxyphenylalanine (L-dopa) also caused an increase in [11C]raclopride
      binding potential, confirming the suggestion that L-dopa plays a more complex
      role than that of dopamine precursor in the nigrostriatal pathway.

PMID- 8525462
TI  - Ontogeny of Fos protein-like immunoreactivity in the suprachiasmatic nucleus.
AB  - This study examined the normal development of neuronal activity in the
      suprachiasmatic nuclei (SCN) of rats between age 3-60 days, using Fos protein
      like immunoreactivity (Fos-LI) as a marker. At age 3 days, Fos-positive nuclei
      are sparsely distributed throughout the SCN. Between age 3-10 days, the density
      of labeled nuclei increases significantly. Fos-LI labeling is maximal at 10 days.
      Between age 10-14 days, the number of labeled nuclei decreases and remains
      relatively constant thereafter, although the intensity of the reaction product
      diminishes as the animal matures. By age 60 days, the number of Fos-LI labeled
      nuclei in the SCN is substantially decreased and is essentially the same as in
      the 3-day-old rat. The appearance of Fos-LI nuclei in the SCN during development
      appears to reflect the development of visual system afferents to the nucleus as
      well as the development of intrinsic SCN synaptology.

PMID- 8525463
TI  - Ligand selectivity of cloned human and rat opioid mu receptors.
AB  - Opiate receptors play major roles in analgesic and euphoric effects of opiate
      drugs. Recent cloning of cDNAs encoding the rodent and human mu receptor revealed
      high homology between the predicted receptors but also some sequence differences.
      To determine if these sequence differences produced significant changes in ligand
      selectivity profiles, we assessed these profiles in expressing COS and CHO cell
      lines using the agonist ligand [125I]IOXY-AGO (6 beta-[125Iodo]-3,14-dihydroxy-17
      methyl-4,5 alpha- epoxymorphinan). This ligand's high specific activity (2,200
      Ci/mmol) and high affinity for mu opioid receptors generated high signal-to-noise
      ratio binding. The resulting ligand-selectivity profiles of the human and rat mu
      receptors reveal modest differences in affinities for morphine and naloxone in
      COS cells but not CHO cells. Ligand-selectivity profiles of the rat and human mu
      receptors were otherwise similar. Interesting differences between these data and
      data previously obtained with the peptide agonist [3H]DAMGO suggest that the
      peptide and alkaloid agonists may label different domains of the mu receptor.

PMID- 8525464
TI  - Subcellular localization of synaptophysin in noradrenergic nerve terminals: a
      biochemical and morphological study.
AB  - The subcellular localization of synaptophysin was investigated in noradrenergic
      nerve terminals of bovine vas deferens and dog spleen and compared with membrane
      bound and soluble markers of noradrenergic storage vesicles. At the light
      microscopical level chromogranin A- and cytochrome b561-immunoreactivity revealed
      an identical and very dense innervation of the entire vas deferens. In the case
      of synaptophysin, most immunoreactivity was found only in the outmost
      varicosities closest to the lumen, which were also positive for chromogranin A.
      Small dense-core vesicles of dog spleen were purified using a combination of
      velocity gradient centrifugation and size exclusion chromatography. Small dense
      core vesicles were enriched 64 times as measured by the noradrenaline content.
      Enrichments for dopamine-beta-hydroxylase were in a similar range. Synaptophysin
      containing vesicles were smaller in size and they did not contain the typical
      noradrenergic markers dopamine-beta-hydroxylase, cytochrome b561, and
      noradrenaline. Instead, they might store adenosine triphosphate (ATP). A greater
      part of synaptophysin immunoreactivity was consistently found at high sucrose
      densities at the position of large dense-core vesicles. We conclude that in the
      noradrenergic nerve terminal: (1) small dense-core vesicles have a membrane
      composition similar to large dense-core vesicles, indicating that the former are
      derived from the latter, and (2) synaptophysin seems not to be present on small
      dense-core vesicles. We suggest the possibility that synaptophysin-containing
      vesicles form a residual population whose role in neurotransmission has been
      taken over by large and small dense-core vesicles following noradrenergic
      differentiation.

PMID- 8525465
TI  - Effects of the putative antidepressant, ABT 200, on the clearance of exogenous
      norepinephrine in rat cerebellum.
AB  - ABT 200 [(RR,SS)-3-phenyl-1-[1',2',3',4'-tetrahydro-5',6'-methylenedioxy- 1'
      naphthalenyl-methyl]-pyrrolidine methanesulfonate] is a potent alpha 2
      adrenoceptor antagonist (Ki = 1.2 nM) with modest norepinephrine uptake-blocking
      activity (IC50 = 841 nM) that is currently under clinical evaluation as an
      antidepressant. The effects of ABT 200, nomifensine (an inhibitor of
      catecholamine uptake), and rauwolscine (a selective alpha 2-adrenoceptor
      antagonist) on the clearance of exogenous norepinephrine in the cerebellum of
      urethane-anesthetized rats was investigated using a vivo electrochemistry.
      Chronoamperometric recordings were continuously made at 5 Hz using Nafion-coated,
      single carbon fiber electrodes. When a calibrated amount of norepinephrine was
      pressure-ejected at 5-min intervals from a micropipette adjacent (290-330 microM)
      to the electrode, transient and reproducible norepinephrine signals were
      detected. In response to systemic ABT 200 (30 mg/kg i.p.) or nomifensine (30
      mg/kg i.p.), the signals increased in both amplitude and time course, indicating
      significant inhibition of the norepinephrine transporter. A lower dose (15 mg/kg
      i.p.) of either ABT 200 or nomifensine had no effect in this paradigm. Local
      application of ABT 200 (400 microM) or nomifensine (400 microM) prior to pressure
      ejection of norepinephrine also significantly increased the amplitude and time
      course of the norepinephrine signals. In contrast, systemic administration of
      rauwolscine (30 mg/kg i.p.) or vehicle solution, and local application of vehicle
      solution, had no effect on the norepinephrine signals. These data indicate that
      at the higher dose evaluated, both ABT 200 and nomifensine inhibit cerebellar
      norepinephrine uptake in vivo.

PMID- 8525466
TI  - Anesthetics decreased the microdialysis extraction fraction of norepinephrine but
      not dopamine in the medial prefrontal cortex.
AB  - We evaluated the effects of chloral hydrate and pentobarbital sodium on the basal
      extracellular concentrations of dopamine (DA) and norepinephrine (NA) as well as
      their in vivo extraction fraction (relative recovery) at the medial prefrontal
      cortex (mPFC) in rats by using zero-net flux microdialysis method. Adult, male
      Sprague-Dawley rats anesthetized with either chloral hydrate (400 mg/kg, i.p.,
      with 80 mg/kg i.v. supplements) or pentobarbital sodium (50 mg/kg, i.p., with 10
      mg/kg i.v. supplements) were used as treatment groups. Conscious rats were used
      as a control group. The basal extracellular concentration and in vivo recovery of
      DA in the conscious group were 2.38 +/- 0.70 nM and 41 +/- 6%. In comparison with
      the chloral hydrate group (1.51 +/- 0.55 nM and 41 +/- 9%) and the pentobarbital
      sodium group (2.81 +/- 1.20 nM and 42 +/- 4%), there were no significant effects
      of anesthesia on the basal extracellular concentration and the in vivo recovery
      of DA at the mPFC. Additionally, the basal extracellular concentration and the in
      vivo recovery of NA in the conscious group were 1.59 +/- 0.37 nM and 51 +/- 8%.
      There also were no significant differences of the basal extracellular
      concentration of NA among these three groups (chloral hydrate group: 4.38 +/-
      1.39 nM; pentobarbital group: 3.67 +/- 0.90 nM). However, the conscious group had
      a higher in vivo recovery than the two anesthetized groups (chloral hydrate
      group: 16 +/- 2%; pentobarbital group: 27 +/- 5%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8525467
TI  - Regulation of neuronal nitric oxide synthase by chronic ethanol ingestion.

PMID- 8525468
TI  - Measurement of DNA integrity and structure in Xenopus embryos in the presence of
      hydroxyurea, actinomycin-D, and triethylenemelamine using the fluorescent probe
      Hoechst 33258.
AB  - Cell health assay of water quality (CHAWQ) is an assay using intracellular
      biomarkers measured by optical techniques. CHAWQ uses embryos of the South
      African clawed frog, Xenopus laevis, and optical transducers of intracellular
      biomarkers to obtain rapid assessment of toxicity to frog embryos. Since the
      biomarkers are common to all cells, CHAWQ can indicate toxicity of different
      classes of chemicals. Among the biomarkers used are 1) the change in synthesis
      rate, 2) the structure, or 3) the environment of DNA. Measurement of DNA to
      detect genotoxicants has previously used extracted DNA or flow cytometry to
      detect alterations in DNA content or configuration. We report the use of viable
      frog embryos and the fluorescent probe Hoechst 33258 to detect the effect of
      three DNA-active chemicals--actinomycin-D, hydroxyurea, and triethylenemelamine
      (TEM)--on DNA in intact embryos. We found that we can detect changes in the DNA
      in the presence of toxicants at concentrations comparable to longer-term assays
      but following a much shorter time of drug exposure. Actinomycin-D caused a
      fluorescence decrease, TEM caused a fluorescence increase, whereas hydroxyurea
      gave a biphasic response. Hydroxyurea caused a decrease at low concentrations and
      an increase at higher concentrations. Concentration-response data for TEM,
      hydroxyurea, and actinomycin-D generated EC50 values of 0.1 mg/ml, 1.4 mg/ml, and
      6.34 micrograms/ml, respectively.

PMID- 8525469
TI  - Morphological transformation induced by glass fibers in BALB/c-3T3 cells.
AB  - Studies were conducted to determine whether 1) glass fibers can induce
      morphological transformation in BALB/c-3T3 cells, 2) the transforming activity of
      glass fibers is related to fiber size, and 3) transformed cells induced by glass
      fibers possess neoplastic properties. In the transformation assay, BALB/c-3T3
      cells were treated with three different types of glass fibers: Manville code 100
      (JM-100, Manville Corp., Denver, CO), Owens-Corning AAA-10 (AAA-10, Owens-Corning
      Corp., Toledo, OH), and Owens-Corning general building insulation (ISL, Owens
      Corning Corp.) fibers. The neoplastic properties were investigated using the soft
      agar cloning and gene transfection methods. All three different glass fibers were
      cytotoxic at high concentrations and induced dose-related increases in
      morphological transformation. The transforming activity was inversely related to
      fiber size, with AAA-10 showing higher activity than JM-100 and JM-100 showing
      higher activity than ISL fiber. Transformed cells induced by glass fibers exerted
      anchorage-independent growth (90%) and DNA transfection-mediated transformation
      (100%). These results indicate that glass fibers are capable of transforming
      mammalian (BALB/c-3T3) cells in vitro as a function of their physical properties
      and that glass fiber-induced transformed cells possess preneoplastic
      characteristics.

PMID- 8525470
TI  - In vitro transforming effect of the fungicides metalaxyl and zineb.
AB  - The cytotoxic effects and the transforming properties of two fungicides,
      metalaxyl and zineb, whose mutagenic or carcinogenic activity has not been
      clarified yet, were analyzed in the in vitro BALB/c 3T3 cell transformation test
      both in the presence and in the absence of an exogenous metabolizing system.
      Zineb was completely detoxified when the exogenous metabolizing system was added
      to the target cells to increase their inherent metabolic capacity. Metalaxyl
      induced cell transformation at any assayed dosage, i.e., 500, 250, and 50
      micrograms/ml, in the presence of bioactivation, and at the highest dosage (500
      micrograms/ml) in the absence of bioactivation. The transforming effect was
      detectable only in the level-II transformation cultures and it was likely linked
      to the induction of additional cell proliferation which allowed obtaining the
      transformation amplification in these experimental conditions.

PMID- 8525471
TI  - Embryotoxicity induced by alkylating agents: 9. Low dose prenatal-toxic risk
      estimation of ethylmethanesulfonate based on no-observed-adverse-effect-level
      risk factor approach, dose-response relationships, and molecular dosimetry.
AB  - Analogously to an earlier study using methylnitrosourea (MNU) the prenatal-toxic
      risk of low doses of ethylmethanesulfonate (EMS) was estimated using different
      procedures, comparatively. First, the risk of low doses was estimated using
      linear extrapolation to zero. When using the variable "all gross structural
      abnormalities" the lowest effective dose in the experiment was 150 mg/kg body wt
      (5.6% incidence), the additional risk over background was calculated to be 5.0%,
      and the hypothetical incidence 0.1% was associated with the dose 3 mg/kg EMS.
      When evaluating "gross structural limb abnormalities," which are not observed in
      controls, the dose associated with the hypothetical incidence 0.1% was 17.4 mg/kg
      EMS. Furthermore, derived from a dose-response study of teratogenicity
      extrapolation to the possible risk of low doses was performed using nonlinear
      mathematical models. In this case, the results obtained are dependent on the dose
      response variable as well as from the statistical approach which was chosen. As
      an example, the values obtained from one evaluation are given: all gross
      structural abnormalities, Weibull transformation, jackknife approach: ED0.1% = 72
      mg/kg EMS. For comparison a "virtually safe dose" was calculated by use of the no
      observed-adverse-effect-level (NOAEL) risk factor approach. The NOAEL under our
      experimental conditions was 100 mg per kg body wt. By using an arbitrarily chosen
      risk factor of 100 a "safe dose" of 1 mg EMS per kg body wt was obtained. In
      addition, molecular dosimetry of the DNA adduct rate of O6-ethylguanine in the 11
      day-old embryos was used. Based on the assumption that a linear correlation
      exists between this specific adduct rate and the incidence of teratogenic
      effects, the hypothetical incidence of 0.1% was associated with a dose of 99
      mg/kg EMS. This value is quite similar to that obtained by extrapolation using
      probit analysis which is in contrast to the results obtained with MNU.

PMID- 8525472
TI  - Evaluation of the OECD 421 reproductive toxicity screening test protocol using 1
      (butylcarbamoyl)-2-benzimidazolecarbamate (benomyl).
AB  - The OECD 421 reproductive toxicity screening test protocol was evaluated using
      the fungicide benomyl as a test compound at 10, 30, or 90 mg/kg per day. Male
      rats showed dose-dependent testicular degeneration after 28 days exposure, as
      expected on the basis of literature data. Dams in the high dose group, exposed
      from 14 days premating to postnatal day 6, had pups with decreased weights at
      postnatal days 1 and 6. Prenatal deaths were increased, but no malformations were
      found. In contrast, in a developmental toxicity test with exposure between
      gestation days 6 and 15, 90 mg/kg induced a high level of postimplantation loss,
      with ophthalmic malformations in the surviving offspring, in agreement with
      literature data. It is suggested that premating exposure in the OECD 421 protocol
      may have induced tolerance to the compound, e.g., by modulation of
      biotransformation in the dam. These findings indicate that the teratogenic
      potential of a compound need not necessarily be revealed using this screening
      test. The OECD 421 protocol appeared sufficiently sensitive to reveal the
      reproductive hazard of benomyl on the basis of prenatal deaths and testicular and
      pup weight effects. However, the absence of congenital anomalies in the offspring
      after benomyl treatment according to the OECD 421 protocol underscores the notion
      that lack of biological activity in the test should not be regarded as evidence
      of lack of activity of a compound on reproductive parameters.

PMID- 8525473
TI  - ZAP-70 and p72syk are signaling response elements through MHC class II molecules.
AB  - Ligation of major histocompatibility complex (MHC) class II antigens expressed on
      antigen-activated human CD4+ T-lymphocytes induces early signal transduction
      events including the activation of tyrosine kinases, the tyrosine phosphorylation
      of phospholipase-C gamma 1 and the mobilization of intracellular calcium. Similar
      responses have been observed in B-cells following stimulation of MHC class II
      molecules, including the increased production of intracellular cAMP. In this
      report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling
      element following cross-linking of HLA-DR in class II+ T-cells, and that the
      homologous tyrosine kinase p72syk is stimulated in B-cells following ligation of
      class II antigens. Antibody mediated co-ligation of the T-cell antigen receptor
      (TCR/CD3) with class II molecules resulted in augmented tyrosine phosphorylation
      of ZAP-70. Comparable to antibody induced receptor ligation, bacterial
      superantigen (SEA and SEB) treatment of HLA-DR+ T-cells stimulated ZAP-70
      tyrosine phosphorylation, consistent with class II transmembrane signaling by
      ligation of HLA-DR and V beta in cis. Modulation of the TCR/CD3 led to abrogation
      of class II induced ZAP-70 tyrosine phosphorylation, but did not result in
      sequestering of ZAP-70 from the cellular cytoplasm. Hyperphosphorylated ZAP-70
      was associated with TCR/CD3 zeta-chain following cross-linking of HLA-DR,
      suggesting a mechanism for the TCR/CD3-dependence of class II induced signals in
      alloantigen-activated human T-cells. In both tonsillar B-lymphocytes and B-cell
      leukemia lines, p72syk was rapidly phosphorylated on tyrosine residues following
      HLA-DR cross-linking. Tyrosine phosphorylation of p72syk induced through ligation
      of either the B-cell antigen receptor or class II molecules was potently
      inhibited by herbimycin A. MHC class II ligation on B-lymphocytes resulted in
      cell death, which was both qualitatively distinct from Fas-induced apoptosis and
      partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II
      molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family of
      tyrosine kinases, leading functionally to a tyrosine kinase-dependent pathway of
      receptor-induced cell death.

PMID- 8525474
TI  - Activation of extracellular signal-regulated protein kinase (ERK/MAP kinase)
      following CD28 cross-linking: activation in cells lacking p56lck.
AB  - T lymphocytes require two signals for activation. Recognition of antigen/MHC
      complexes by the T cell receptor delivers the first signal, while a second
      signal, delivered by the cell surface receptors CD80 and/or CD86 binding to the T
      cell surface molecule CD28, has been shown to be effective for the initiation of
      effective T cell responses. While some of the cytoplasmic effector molecules
      involved in T cell receptor signaling is known, little is known regarding those
      involved in the co-stimulation of T cells by CD28. Using the T cell leukemic cell
      line Jurkat as a model for T cell activation, we demonstrate that cross-linking
      CD28 using monoclonal antibodies causes tyrosine phosphorylation and activation
      of MAP kinase/ERK. This activation was rapid, peaking at approximately 5 minutes
      post CD28 cross-linking, and transient. Activation of MAP kinase/ERK occurred 3
      fold less efficiently in a Jurkat line lacking functional p56lck (JCAM.1), and
      was almost undetectable in a line lacking CD45 (J45.01). These results suggest
      that CD28 cross-linking can activate intracellular signaling pathways via several
      different tyrosine kinases. Thus CD28 signaling can activate src family kinases
      lck and fyn, as well as the Tec family kinase emt/itk. Activation of any one or a
      combination of these tyrosine kinases may be sufficient for the activation of
      MAPK following CD28 cross-linking. Activation of MAPK has been shown to cause
      activation of AP-1 and other transcription factors via serine and/or threonine
      phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525475
TI  - The HLA-A3, Cw6,B47,DR7 extended haplotypes in salt losing 21-hydroxylase
      deficiency and in the Old Order Amish: identical class I antigens and class II
      alleles with at least two crossover sites in the class III region.
AB  - The HLA-B47,DR7 haplotype in congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency contains a deletion of most of the active CYP21 gene and
      the entire adjacent C4B gene. The C4A gene produces a protein which is
      electrophoretically C4A but antigenically C4B. In the Old Order Amish, the HLA
      B47,DR7 haplotype contains no deletion, but is immunologically identical to the
      CAH haplotype in both areas flanking the crossover region. We compared some of
      the genes in the MHC Class II and Class III regions in the Amish and CAH-linked
      haplotypes to define further the relationships between the two. The complement
      factor B (Bf) proteins differed, but no Bf RFLPs were identified. The complement
      factor 2 genes exhibited different BamHI RFLPs. Analyses of the tumor necrosis
      factor-alpha genes revealed the same NcoI restriction patterns. The RD genes
      contained microsatellites of the same size. Portions of the MHC Class II DR and
      DQ, and Class III CYP21 and C4 alleles were sequenced. The exon 2 sequences of
      DQ2 and DR7 were identical in the two haplotypes. In the Amish haplotype, both
      CYP21 and C4 gene pairs were present and functionally normal. The CAH haplotype
      had two sequence crossovers: from CYP21P to CYP21 in the 7th intron, and from C4A
      to C4B between codons 1106 (exon 26) and 1157 (exon 28). A model is proposed
      which accounts for the CAH-linked mutant haplotype arising from a nonmutant
      homologue via three crossings-over.

PMID- 8525476
TI  - Automated, solid-phase sequencing of DRB region genes using T7 sequencing
      chemistry and dye-labeled primers.

PMID- 8525477
TI  - Predictability of alloreactivity among unrelated individuals: role for HLA-DPB1.
AB  - We compared the mixed lymphocyte culture reaction (MLR-1) among unrelated
      individuals who are carriers of the extended haplotype [HLA
      B8,SC01,DR3,DRB1*0301,DQB1*0201] on one chromosome and the generic specificity
      HLA-DR4 on the second chromosome. Genomic DNA samples from the same individuals
      were also analyzed for HLA-DRB1, DQB1 and DPB1 alleles by PCR and SSOPH typing
      and for DOB polymorphism by RFLP. HLA-DRB1 alleles, in paired MLR responses
      between unrelated individuals indicated that matching of HLA-DRB1 was a better
      predictor of non-reactivity than identity in HLA-DR generic types, (43% vs 22%).
      Moreover, 90% of the DRB1 matched pairs had nonreactive and weakly reactive MLR,
      whereas only 37% of DRB1 mismatched unrelated individuals gave weak or no
      reactions. Matching for HLA-DRB1 and HLA-DPB1 alleles eliminates a significant
      number of cell mixtures with MLR-I reactivity. Furthermore, some DPB1 mismatches,
      but not all, do not seem to elicit MLR-I reactivity.

PMID- 8525478
TI  - Definition of HLA-C alleles using sequence-specific oligonucleotide probes (PCR
      SSOP).
AB  - Many new HLA-C locus alleles have recently been identified by DNA sequencing, and
      a molecular based method for their detection using PCR with sequence specific
      primers has been reported. However, other methods may be more appropriate for the
      identification of C locus alleles in larger studies. Here we describe one such
      system, based on PCR sequence specific oligonucleotide probes, (SSOP) for C locus
      typing. Advantages of SSOP typing compared to SSP are that it is easier to detect
      new alleles, more cost effective and less time consuming. We have developed a DNA
      typing method to identify the broad C locus antigens (including those not yet
      defined serologically) using a minimum of probes with one amplification. We use a
      C locus specific sense primer in exon 2 and a consensus antisense primer in exon
      3, in a two-step PCR, giving a product of 710 bp. Probes were designed with
      similar melting temperatures (54-56 degrees C) that would identify as many
      alleles as possible. The method was established using DNA from B lymphoid cell
      lines of known C locus type, mostly 10th workshop homozygous cell lines, plus as
      many other sequenced cell lines as possible. The system was able to correctly
      identify their C locus types using only 26 probes. DNA was tested from a panel of
      serologically typed individuals which included many different heterozygous
      combinations. We found a high concordance of results, with all discrepancies
      being additional antigens identified by molecular typing, filling in serological
      blanks. We can identify all common heterozygote combinations using this method.

PMID- 8525479
TI  - Allelic heterogeneity of HLA-B35 subtypes in different populations as assessed by
      DNA typing.
AB  - HLA-B35, a class I antigen differentially associated to several diseases in
      different ethnic groups, comprises at least eight alleles which differ among them
      by one to six amino acids. In the present work a rapid DNA typing procedure was
      used to investigate the distribution of the various HLA-B35 alleles in different
      populations. The approach is based on a group-specific PCR amplification of a set
      of closely related HLA-B alleles sharing a Thr in position 45 of the alpha-1
      domain. The amplified DNA was then hybridized to a panel of sequence-specific
      oligonucleotide (SSO) probes designed to recognize the polymorphic residues in
      previously reported HLA-B35 subtypes. This methodology was successfully tested in
      100 individuals of four different populations, previously typed by serology as
      HLA-B35, and in six reference panel cells of the 10th International
      Histocompatibility Workshop. HLA-B*3501 was the predominant subtype in all
      populations. B*3502, B*3503 and, to a lesser extent B*3508, were also found.
      Among Mexican Mestizos, thirteen individuals had patterns of SSO hybridization
      suggestive of new B35 alleles. The evolutionary considerations on the different
      B35 alleles and their extended B35,Cw4 haplotypes are discussed.

PMID- 8525480
TI  - Identification of a novel HLA-B40 allele (B*4008) in a patient with leukemia.

PMID- 8525481
TI  - A complete exon 2 sequence of the HLA-DPA1*02012 allele.

PMID- 8525482
TI  - Characterization of a new DPB1 allele (DPB1*5701) isolated from a Caucasian
      individual.

PMID- 8525483
TI  - HLA and TAP associations in Chinese systemic lupus erythematosus patients.

PMID- 8525484
TI  - HLA class I nucleotide sequences, 1995.

PMID- 8525485
TI  - HLA class II region nucleotide sequences, 1995.

PMID- 8525486
TI  - Effect of methylmercury (CH3HgCl) injury on nitric oxide synthase (NOS) activity
      in cultured human umbilical vascular endothelial cells.
AB  - The effects of methylmercury (CH3HgCl; MeHg) on the production of nitric oxide
      (NO) and the activity of the enzyme, nitric oxide synthase (NOS), in cultured
      human umbilical vascular endothelial cells (HUVEC) were examined. To assess the
      production of NO by HUVEC, platelet aggregation experiments were performed using
      cuvettes lined with HUVEC. Thrombin (0.05 U/ml)-induced platelet aggregation was
      inhibited in HUVEC pretreated with indomethacin (1 microM), an inhibitor of the
      cyclo-oxygenase pathway. The anti-platelet aggregatory effect of HUVEC treated
      with indomethacin was decreased dose-dependently by 48-h pretreatment with MeHg
      (0.5-2 microM). The effect of MeHg on the NADPH diaphorase staining of NOS in
      HUVEC showed dose-dependent cytotoxicity in regard to NOS activity. These
      findings suggest that MeHg inhibits the production of NO by HUVEC, an action
      which may be dependent on the cytotoxic effect exerted by MeHg on NOS activity.

PMID- 8525487
TI  - Pretreatment with p-aminohippurate inhibits the renal uptake and accumulation of
      injected inorganic mercury in the rat.
AB  - The effects of intravenous pretreatment with the organic anion p-aminohippurate
      (PAH) on the disposition of intravenously administered inorganic mercury in the
      kidneys, liver and blood were evaluated in rats. In dose-response experiments,
      the renal uptake (and/or accumulation) of mercury, 1 h after the injection of a
      nontoxic 0.5 mumol/kg dose of mercuric chloride (HgCl2), was significantly
      reduced in rats when a 1.0, 3.3 or 10 mmol/kg dose of PAH was administered 5 min
      prior to the injection of HgCl2. This reduction was due to reduced uptake of
      mercury in both the renal cortex and outer stripe of the outer medulla. Near
      maximal inhibition appeared to be achieved with the 10 mmol/kg dose of PAH.
      Inhibition of the uptake (an/or accumulation) of mercury in the renal cortex and
      outer stripe of the outer medulla, 1 h after the injection of the nontoxic dose
      of HgCl2, was also detected in experiments where HgCl2 was injected 5, 30, 60 or
      180 min after pretreatment with a 10 mmol/kg dose of PAH. The renal uptake of
      mercury was inhibited significantly when the nontoxic dose of inorganic mercury
      was administered 5, 30, or 60, but not 180 min after pretreatment with the 10
      mmol/kg dose of PAH. In another experiment, the renal burden of mercury was
      significantly reduced for 24 h when pretreatment with a 10 mmol/kg dose of PAH
      was administered 5 min prior to the injection of HgCl2. Pretreatment with PAH did
      not have an effect on the hepatic disposition of mercury, but it did cause a
      significant increase in the fraction of mercury present in the plasma of blood.
      In summary, the findings in the present study indicate that pretreatment with PAH
      inhibits the renal uptake of injected inorganic mercury in a dose-dependent and
      time-dependent manner. In addition, the findings tend to indicate that some
      fraction of the mercury that enters into renal tubular epithelial cells is by a
      mechanism involving the organic anion transport system.

PMID- 8525488
TI  - N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes in primary cultures of rabbit
      kidney proximal tubule cells: a cellular model for studies on nephrotoxicity?
AB  - N-Acetyl-beta-D-glucosaminidase (NAG) isoenzyme profile in primary cultures of
      rabbit kidney proximal tubule cells was studied. Confluent cells had high levels
      of NAG activity, but ion exchange chromatography showed that the NAG isoenzyme
      profile in cultured cells was different from that of rabbit renal cortex
      homogenates and freshly isolated cells. Confluent cultured cells contained an
      atypical acidic isoform, absent in homogenates and freshly isolated cells in
      which the predominant isoform is NAG-A (a heterodimer alpha beta). The fact that
      this atypical isoform was able to hydrolyse the synthetic substrate 4
      methylumbelliferyl-beta-N-acetylglucosaminide-6-sulphate indicated that it
      probably was an alpha-subunit homodimer. These results suggest subunit
      rearrangement within NAG polypeptide chains linked to down-regulation of beta
      subunit production in cultured rabbit proximal cells. The change in isoenzyme
      profile in cultured cells may make it difficult to use primary cultures of rabbit
      proximal tubule cells to establish correlations between in vitro and in vivo
      studies using NAG isoenzymes as a nephrotoxicity index, as illustrated by the
      effects of gentamicin.

PMID- 8525489
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin blocks the physiological regulation of
      hepatic phosphoenolpyruvate carboxykinase activity in primary rat hepatocytes.
AB  - It has been previously reported that TCDD dose-dependently reduces the activity
      of PEPCK, the rate-limiting enzyme of hepatic gluconeogenesis. To further
      investigate the mechanism, whereby TCDD decreases PEPCK activity, we studied the
      effect of TCDD on PEPCK activity in primary rat hepatocytes (PRH). PRH were
      isolated from male Sprague-Dawley rats by collagenase perfusion and incubated on
      collagen-coated culture dishes in medium M199 containing 1 nM insulin. Cells were
      pretreated with dexamethasone (100 nM) 8 h before PEPCk induction was initiated
      by addition of glucagon (10 nM) and concurrent withdrawal of insulin. This
      hormonal treatment induced the enzymatic activity of PEPCK in control cells about
      2-fold within 8 h. This PEPCK induction regimen was used to perform two sets of
      experiments. In the first set of experiments, rats were pretreated with TCDD (125
      micrograms/kg p.o. in corn oil, 4 ml/kg) 4 days prior to isolation of PRH. This
      resulted in a complete block of the glucagon-dependent induction of PEPCK in PRH
      from TCDD-pretreated animals. In the second set of experiments, TCDD (100 nM) was
      added directly to the PRH either 24 or 48 h prior to the induction regimen.
      Incubation of PRH with TCDD 24 h prior to initiation of the induction regimen
      resulted in a slight decrease in the degree of PEPCK induction when compared to
      controls. However, treatment of PRH with TCDD 48 h prior to initiation of the
      induction regimen almost completely blocked PEPCK induction. It is, therefore,
      suggested that the effect of TCDD on liver PEPCK activity is due to a direct
      effect on liver cells and is not mediated by factors from outside the liver.

PMID- 8525490
TI  - Lead affects steroidogenesis in rat Leydig cells in vivo and in vitro.
AB  - Lead is known to impede the male reproductive function, however, the mechanisms
      through which the adverse effects are mediated are not clearly elucidated. In
      order to get insight into those mechanisms, we have examined the effects of lead
      on the biosynthesis of steroid hormones by Leydig cells in the rat. To determine
      whether lead has a direct action on Leydig cells, we have compared the
      concentrations of testosterone secreted by Leydig cells in ex vivo experiments
      after animals had been injected with high doses of lead and in vitro experiments
      with Leydig cells from normal rats maintained in culture in presence or absence
      of lead. In ex vivo experiments male Spargue-Dawley rats were injected i.p. with
      lead acetate (8 mg lead/kg/day, 5 days a week for 5 weeks) or with sodium
      acetate. Testosterone production by Leydig cells isolated and maintained in
      culture for 48 h was then assessed under basal conditions or after stimulation by
      human chorionic gonadotrophin (hCG). Both basal and hCG-stimulated testosterone
      production dropped by 59% and 37%, respectively, with Leydig cells from lead
      exposed rats. For in vitro experiments, cultures of Leydig cells from control
      rats were exposed to various concentrations of lead acetate for different
      periods. Dose and time-dependent reductions of testosterone level were observed
      in the culture medium. The effective doses of hCG for maximal and half-maximal
      testosterone production did not change, indicating that the sensitivity of Leydig
      cells to hCG was not impaired by exposure to lead in vitro. Progesterone
      production was also decreased after this exposure. The negative effect of lead on
      testosterone and progesterone production was correlated with the lower expression
      of the enzymes cytochromes P450scc (CYP11A1) and P450c17 (CYP17) and 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD) involved in steroid hormone
      biosynthesis, as shown by immunohistochemistry. Ultrastructural alterations of
      the smooth endoplasmic reticulum observed after lead administration might be
      correlated with the lower expression of the microsomal enzymes P450c17 and 3 beta
      HSD. Our results indicate that lead can adversely affect the Leydig cell function
      by impairing directly steroidogenesis.

PMID- 8525491
TI  - An international evaluation of the murine local lymph node assay and comparison
      of modified procedures.
AB  - The murine local lymph node assay is a predictive test for the identification of
      skin-sensitizing chemicals. The method has been the subject both of national
      inter-laboratory studies and of extensive comparisons with guinea pig tests. In
      the investigations reported here, the local lymph node assay has been evaluated
      further in the context of an international study comprising five independent
      laboratories. In addition, the influence of minor modifications to the standard
      assay procedure on the performance of the test has been examined. The modified
      procedures investigated were exposure of mice for 4 rather than 3 consecutive
      days, excision of lymph nodes 4 rather than 5 days after the initiation of
      exposure and the use of an alternative isotope. All five laboratories,
      irrespective of whether the standard or a modified protocol was used, were able
      to identify accurately, and with comparable sensitivity, potassium dichromate and
      2,4-dinitrochlorobenzene as skin sensitizers. Using standard criteria, none of
      the laboratories recorded positive responses with methyl salicylate, a non
      sensitizer. In the standard protocol, lymph nodes are pooled for each
      experimental group and the vigor of responses measured as a stimulation index
      relative to vehicle controls. A stimulation index of 3 or greater is considered
      to indicate skin-sensitizing potential. One further modification adopted by three
      of the laboratories was to analyze nodes from individual animals and, thereby,
      permit statistical evaluation. This allowed a direct comparison of statistical
      significance with the conventional stimulation index as criteria for a positive
      response. The data indicate that, while statistical evaluation may provide, in
      some instances, for small increases in sensitivity, this may be at the expense of
      some loss of selectivity. There are, however, insufficient data presently to draw
      firm conclusions regarding the relative value of statistical analysis. These
      studies demonstrate that the local lymph node assay is sufficiently robust to
      accommodate minor procedural and technical modifications without material changes
      in test performance.

PMID- 8525492
TI  - Pulmonary toxicity of nickel subsulfide in F344/N rats exposed for 1-22 days.
AB  - Repeated inhalation of nickel subsulfide (Ni3S2) by F344/N rats for 3 months
      results in chronic active inflammation in the lung and atrophy of the olfactory
      epithelium. The primary purpose of this study was to determine early responses of
      the respiratory tract to inhaled Ni3S2 in rats and to track the course of
      development of such lesions in rats exposed for up to 22 days. A secondary
      purpose was to obtain an improved estimate of the half-time for clearance of Ni
      from Ni3S2-exposed lungs. Groups of F344/N rats were exposed to 0, 0.6 or 2.5 mg
      Ni3S2/m3, 6 h/day for 1-22 days. Histopathological changes in nose and lung, as
      well as biochemical and cytological changes in lung, as measured in
      bronchoalveolar lavage fluid (BALF) and lung tissue, alveolar macrophage (AM)
      viability and Ni concentration in lung were evaluated. Inflammatory lung lesions
      in rats exposed to 2.5 mg Ni3S2/m3 peaked in intensity after 4 days of exposure.
      Minimal degeneration of the olfactory epithelium was noted in the 2.5 mg Ni3S2/m3
      exposed rats after day 4 of exposure, with atrophy of the olfactory epithelium
      occurring in rats killed at 22 days. Lactate dehydrogenase, beta-glucuronidase
      and total protein in BALF were significantly elevated within 7 days of exposure
      while alkaline phosphatase activity was significantly depressed. AM viability was
      significantly reduced after 2 days of exposure. Concentrations of Ni in lung
      increased rapidly during the first 7 days of exposure, but more slowly
      thereafter. Lung burden data from this and a previous study suggest a clearance
      half-time for Ni of 3.5-8 days. Results indicate that Ni3S2 is relatively soluble
      in lung and inhalation of concentrations near the current Threshold Limit Value
      of 1 mg Ni/m3 can produce detrimental changes in the respiratory tract of rats
      after only a few days of exposure.

PMID- 8525493
TI  - Lobar variation of carbon tetrachloride hepatotoxicity in the rat.
AB  - The lobar variation in carbon tetrachloride-induced liver damage in the rat has
      been assessed by use of a systematic random sampling protocol and quantitative
      morphometry. A random inter-animal lobar variation in severity of damage was
      apparent, in contrast with the results obtained previously in which sampling
      bias, small animal numbers, and lack of fully quantitative measurement were
      apparent. The route of administration (oral vs. i.p.) did not influence these
      findings.

PMID- 8525494
TI  - A study of the nephrotoxicity of three cephalosporins in rabbits using 1H NMR
      spectroscopy.
AB  - Male New Zealand White rabbits received a single intravenous injection of 125
      mg/kg cephaloridine, 500 mg/kg cefoperazone or 1000 mg/kg cephalothin.
      Histological examination of kidneys at 48 h post-dose confirmed the presence of
      bilateral necrosis of the proximal convoluted tubules in the cephaloridine
      treated animals. 1H-NMR urinalysis of cephaloridine-treated rabbits detected drug
      related resonances, decreased hippurate and increased glucose at 0-24 h post-dose
      accompanied by elevated levels of lactate, glycine, citrate, glutamine/glutamate
      and alanine at 24-48 h post-dose. No histopathological changes were observed
      following administration of cefoperazone or cephalothin. 1H-NMR spectra of urine
      collected from these animals showed drug-related resonances and decreased
      hippurate levels at 0-24 h post-dose, and increased glucose levels at 24-48 h
      post-dose. Analysis of urine by conventional clinical-chemistry failed to reveal
      any statistically significant differences between the treatment groups. Under the
      conditions of this study, the nephrotoxic effects of cephaloridine and the
      minimal effects of cefoperazone and cephalothin could be clearly distinguished by
      1H-NMR urinalysis but not by conventional urinalysis.

PMID- 8525495
TI  - Mutagenicity and toxicity studies of p-phenylenediamine and its derivatives.
AB  - The mutagenicity of p-phenylenediamine and its derivatives was tested using Ames
      Salmonella strains TA98 and TA100. p-Phenylenediamine was weakly mutagenic to
      TA98 with metabolic activation. 2-Nitro-p-phenylenediamine was directly mutagenic
      to both strains, while 2-methyl-p-phenylenediamine required S9 mix. All the test
      compounds induced a dose-related increase in chromosomal aberrations in Chinese
      hamster ovary (CHO) cells in the absence of the S9 mix. The mutagenicity and
      toxicity of these compounds did not correlate with their oxidation potentials, or
      any other tested physicochemical properties including the energy difference
      between the lowest unoccupied and the highest occupied molecular orbital,
      ionization potential, and dipole moment.

PMID- 8525496
TI  - Absorption of 3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H] furanone (MX) through
      rat small intestine in vitro.
AB  - The intestinal absorption of 3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H]
      furanone (MX), a highly mutagenic furanone found in chlorinated waters, was
      studied using an in vitro everted rat gut sac system, using reverse mutation in
      Salmonella typhimurium to detect mutagens transported from the mucosal to the
      serosal compartments. Absorption was measurable, but limited, with significant
      increase in bacterial revertants (serosal compartment) noted at a dose of 50
      micrograms/ml MX (mucosal compartment, p < 0.05). Gut sac incubation with MX and
      glutathione (GSH, 1.0 mM) resulted in no detectable absorption of mutagens.
      Preincubation with diethylmaleate to deplete mucosal GSH resulted in increased
      absorption of MX-derived mutagens compared to controls (a significant induction
      of revertant colonies was noted at a dose of 25 micrograms/ml MX p < 0.05). Gut
      sac incubation with chlorinated fulvic acids resulted in no detectable absorption
      of mutagens. In vitro studies to assess the possibility of beta-lyase activation
      of the postulated MX-GSH conjugate showed no mutagenic activation.

PMID- 8525497
TI  - Fasting for less than 24 h induces cytochrome P450 2E1 and 2B1/2 activities in
      rats.
AB  - Cytochrome P450 (CYP) 2E1 activity is induced after 24 h of fasting but no
      information is available for shorter fasting periods. We investigate the
      induction of CYP 2E1, 2B1/2 and 1A1 in young adult male F344 rats after 8, 16 and
      24 h of fasting compared to control. Liver microsomes were analyzed for the
      following enzyme activities: p-nitrophenol hydroxylase (PNP) for CYP 2E1,
      pentoxyresorufin-O-dealkylase (PROD) for CYP 2B1/2 and ethoxyresorufin-O
      deethylase (EROD) for CYP 1A1. After each fasting interval, the activities per mg
      microsomal protein for PNP and PROD increased but the activity of EROD remained
      unchanged. Western blots for CYP 2E1 and CYP 2B1 showed increases comparable to
      the PNP and PROD activities, respectively. On a whole organ basis, increases were
      found for PNP and PROD activities, while decreases were found for EROD activity
      and total microsomal protein. The results are consistent with an induction of CYP
      2E1 and CYP 2B1/2 activities after as little as 8 h of fasting.

PMID- 8525498
TI  - Comparative studies of two organophosphorus compounds in the mouse.
AB  - A rodent model, the albino mouse, was used to investigate the in vitro and in
      vivo capacity of 2 organophosphate (OP) compounds, mipafox and ecothiopate, to
      inhibit enzymes considered to be involved in the mechanisms of OP toxicity.
      Mipafox and ecothiopate were chosen as model compounds because the former can
      produce a delayed neuropathy whereas the latter does not. Mipafox (110 mumol/kg,
      s.c.) inhibited brain acetylcholinesterase (AChE), neuropathy target esterase
      (NTE) and phenylvalerate hydrolases by 58, 64 and 65%, while diaphragm AChE and
      phenylvalerate hydrolases were inhibited by 66 and 80%, respectively. In
      contrast, ecothiopate (0.5 mumol/kg) had no effect on brain NTE or on brain or
      diaphragm phenylvalerate hydrolases. At the same time, diaphragm AChE was
      inhibited by 60% while brain AChE activity had increased by 15% of control.
      Mipafox was a potent inhibitor of AChE and NTE in vitro. Although ecothiopate was
      a highly potent anti-ChE in vitro, it had no inhibitory effect on NTE.

PMID- 8525499
TI  - Metabolism of (+)-trans-benzo[a]pyrene-7,8-dihydrodiol by 3-methylcholanthrene
      induced rat liver homogenates.
AB  - Using a new sensitive reverse-phase HPLC assay with on-line radioactivity
      detector, metabolism of (+)-trans-benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol) to
      the ultimate carcinogen benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE) was
      studied using 3-methylcholanthrene-induced rat liver homogenates. The results
      demonstrate that the stereoselectivity of B[a]PDE formation is a function of the
      concentration of the cellular constituents in the incubation media. At more
      dilute concentrations of the homogenate, the ratio of anti- to syn-B[a]PDE was
      the highest and decreased as the homogenate protein was increased in the
      incubation medium. However, there was a marked and parallel decrease of free
      B[a]PDE and DNA-bound radioactivity with increasing concentrations of cellular
      constituents in the incubation medium. The decreased DNA-bound radioactivity
      appears to be due to the preferential binding of B[a]PDE to glutathione and to
      proteins as the homogenate concentration was increased in the incubation media.
      These results indicate that liver homogenates, while apparently preserving the
      function of microsomes, present additional opportunities to study the
      interrelationship among cytochrome P450 monooxygenase activity, water-soluble
      conjugates, and binding of B[a]P diol metabolites to macromolecules in the study
      of benzo[a]pyrene-induced carcinogenesis.

PMID- 8525500
TI  - Biochemical, pathologic and morphometric alterations induced in male B6C3F1 mouse
      liver by short-term exposure to dichloroacetic acid.
AB  - Dichloroacetic acid (DCA) is a complete hepatocarcinogen and tumor promoter in
      the male B6C3F1 mouse. Published reports indicate that the compound is non
      genotoxic. This study examines possible non-genotoxic (epigenetic) mechanisms by
      which DCA elicits its carcinogenic response. Correlative biochemical, pathologic
      and morphometric techniques are used to characterize and quantify the acute,
      short-term response of hepatocytes in the male B6C3F1 mouse to drinking water
      containing DCA. Cellularity, [3H]thymidine incorporation, DNA concentration,
      nuclear size, and binuclearity are evaluated in terms of level of exposure (0,
      0.5 and 5 g/l) and length of exposure to DCA. The dose-related alterations in
      hepatocytes of animals exposed to DCA for 30 days or less indicate that short
      term exposure to DCA results in inhibition of mitoses, alterations in cellular
      metabolism and a shift in ploidy class. Thus, DCA carcinogenesis may involve
      cellular adaptations, development of drug resistance and selection of
      phenotypically altered cells with a growth advantage.

PMID- 8525501
TI  - The localization of DMPO spin adducts of OH in endothelial cells exposed to
      hydrogen peroxide.
AB  - Examination by electron spin resonance (ESR) spectroscopy revealed the
      localization of 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) spin adducts of hydroxyl
      radicals (.OH) produced by bovine endothelial cells exposed to hydrogen peroxide.
      Addition of 10 mM chromium oxalate, a line-broadening agent, to the reaction
      mixture virtually abolished the signal of DMPO-OH spin adducts. Moreover, the
      spin adducts were recovered in the filtrated fraction of the cell suspension. We,
      therefore, concluded that the location of DMPO-OH due to .OH radicals produced by
      endothelial cells was extracellular. Contrastingly, the site of formation of DMPO
      OH was confirmed to be intracellular by the effect of Desferal, an iron chelator,
      and the effect of poly(ethylene glycol), an extracellular scavenger of OH
      radicals, as previously reported. The DMPO-OH adducts in the cell suspension
      mixture were degraded by a cyanide sensitive pathway and they were apparently
      more unstable than in the extracellular fraction. The initial amount of DMPO-OH
      adducts formed in endothelial cells could potentially be monitored by the DMPO-OH
      signals in the extracellular reaction mixture better than those in the cell
      suspension mixture.

PMID- 8525502
TI  - Differential effects of T cell receptor ligation of TCR gamma delta thymocyte
      development in fetal thymic organ culture.
AB  - Fetal thymus organ culture system (FTOC), a well-known model used for the study
      of TCR alpha beta development, was employed to study TCR gamma delta cell
      development. It was found that different waves of TCR gamma delta cells develop
      from precursors within the fetal thymi at the time in vitro culture. Subsets of
      fetal thymocytes were analyzed by flow cytometry and 2-D gel biochemical analysis
      was performed. After 5 days in FTOC, V gamma 3+ and V gamma 2+ cells were
      dominant. By day 12 FTOC, the absolute number of V gamma 3+ cells decreased while
      V gamma 2+ and V gamma 4+ cells became dominant. These observations suggest that
      the thymic micro-environment affects the thymic waves of TCR gamma delta subsets.
      Furthermore, the effect of TCR/antigen interaction in the development of TCR
      gamma delta cells was examined with anti-TCR mAbs added into the FTOC. Anti-CD3
      mAb added to day 5 and day 12 FTOC inhibited TCR gamma delta development,
      especially V gamma 4+ cells. On the other hand, V gamma 2+ cells were relatively
      resistant to the addition of anti-TCR mAb. The reduction of TCR gamma delta+
      thymocytes was not due to the modulation of TCR molecules and could be reversed
      by Cyclosporin A (CsA). These results suggest that TCR ligation negatively
      regulates the development of TCR gamma delta cells in a V gamma-specific manner.

PMID- 8525503
TI  - Effects of cytokines on HIV-1 production by thymocytes.
AB  - The thymus is essential for normal T cell development and is particularly active
      during fetal and postnatal life. Here we describe in vitro studies of HIV
      infected thymocytes cultured with cytokines normally produced in the thymus.
      Virus expression was determined by measuring p24 antigen levels in the culture
      supernatants. Addition of IL-2+IL-4 and IL-4+IL-7 to the HIV-infected cultures of
      both fetal and postnatal thymocytes resulted in various levels of synergistic
      expression of p24 antigen. When differences in phenotype between HIV-infected and
      non-infected (sham-treated) cultures from the same specimen were evaluated, there
      was a decrease in the percentages and absolute numbers of CD4-bearing cells in
      HIV-infected thymocytes cultured with IL-2+IL-4. Studies were done to determine
      if synergy in HIV expression was mediated by activation, proliferation or
      induction or suppression of other cytokines. We found a higher percentage of
      activated CD4+CD8+/high cells in thymocytes cultured with IL-2+IL-4 and IL-4+IL-7
      than in thymocytes cultured with IL-2+IL-7. Proliferation was higher in
      thymocytes cultured with cytokine combinations but did not correlate with those
      conditions showing synergy. IL-4 reduced IFN-gamma production by thymocytes
      cultured with IL-2 in both HIV-infected and non-infected thymocytes. In addition,
      exogenous IFN-gamma decreased p24 expression by HIV-infected thymocytes when
      cultured with IL-4 alone, with IL-2+IL-4 or IL-4+IL-7. These results suggest that
      suppression of IFN-gamma by IL-4 may combine with cell activation and
      proliferation to produce synergy of virus expression observed with IL-2+IL-4 and
      IL-4+IL-7.

PMID- 8525504
TI  - Characterization of TNF receptors on human thymocytes.
AB  - Although tumor necrosis factor-alpha (TNF) is constitutively expressed in human
      and mouse thymus, the effects of TNF on thymocyte proliferation, differentiation
      and survival suggest that its influence in the thymus is complex. To determine if
      this complexity results from changes in the expression of the two TNF receptors
      during thymocyte differentiation, we examined the expression of the 55 kDa TNF
      receptor (TNF-R1) and the 75 kDa TNF receptor (TNF-R2) on postnatal human
      thymocytes. Both TNF-R1 and TNF-R2 mRNA were found in resting human thymocytes by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Using mAb which
      specifically react with the respective TNF receptors and a highly sensitive,
      three-step method of immunofluorescence, cell surface TNF-R1 was detected on the
      vast majority of thymocytes. In contrast, detectable cell surface TNF-R2 was
      present on a mean of only 12.9% of thymocytes. TNF conjugated to phycoerythrin
      (TNF-PE) also reacted with a small population of thymocytes and was found to
      specifically block binding of the TNF-R2 mAb and not the TNF-R1 mAb, implicating
      preferential binding of TNF-PE to TNF-R2. Using dual-color immunofluorescence
      with TNF-PE we found that the population of cells which express TNF-R2 also
      express high levels of the TCR alpha, beta-CD3 complex, CD4 or CD8, and IL-2
      receptor alpha chain. Thus, immature (TCRneg/low) thymocytes express TNF-R1 while
      mature (TCRhigh) thymocytes can also express TNF-R2. This differential expression
      of TNF receptors provides a mechanism for distinct effects of TNF on immature vs.
      mature thymocytes.

PMID- 8525505
TI  - A novel culture system for induction of T cell development: modification of fetal
      thymus organ culture.
AB  - We have previously found that the development of T cells predominantly of the T
      cell receptor alpha beta T cell lineage, which is comparable to that in the organ
      culture (OC) of fetal thymus at the air-medium border (AMB), could be induced in
      submersion OC of murine fetal thymus if the cultivation was performed in an
      environment containing O2 at 60-80%. This culture method is named high oxygen
      submersion (HOS)-OC. In the present work, we established a culture system where T
      cell development can be induced from thymic as well as fetal liver progenitors by
      cocultivating them in a 96-well U-bottom plate with a deoxyguanosine (dGuo)
      treated fetal thymus lobe under HOS conditions. Differentiation and growth of T
      cells in this culture system were comparable to those seen in the previously
      devised micro i.t. system, where progenitor cells were injected with a
      microinjector into dGuo-treated lobes and were cultured under AMB conditions. A
      similar level of T cell development was induced by cocultivating such progenitors
      with small fragments of thymus lobes under HOS conditions. Moreover, it was
      possible to induce T cell development by culturing fetal thymus cells with thymic
      stromal cells prepared by treating dGuo-treated lobes with trypsin plus EDTA in a
      V-bottom plate under HOS conditions.

PMID- 8525506
TI  - Thymocyte and T cell apoptosis: is all death created equal?
AB  - During thymocyte development, potentially autoreactive thymocytes are eliminated
      by a process known as apoptosis or programmed cell death. While it has long been
      known that this clonal elimination or negative selection of thymocytes expressing
      T cell receptors with high affinity for self antigens plays a major role in
      preserving self tolerance, it is now apparent that apoptosis may also play an
      active role in maintaining peripheral T cell tolerance. Although it is clear that
      apoptosis plays a major role in shaping the immune response, the mechanisms
      responsible for its induction and the regulatory mechanisms that influence
      susceptibility to cell death are not well characterized. In this article, we will
      concentrate on some of the most recent findings in this area. In particular, we
      will emphasize the protective 'rheostat' mechanism exemplified by the Bcl-2
      family members, and the role of Fas in activation-induced apoptosis. In addition,
      we will compare the physiologic signals that trigger apoptosis in thymocytes and
      peripheral T cells, and discuss whether central and peripheral deletion are
      regulated by similar or distinct mechanisms.

PMID- 8525507
TI  - Developmental regulation of cAMP signaling pathways in thymocyte development.
AB  - Major developmental transitions in thymocyte differentiation are accompanied by
      sharp alterations in cAMP metabolism. We have analyzed the cAMP accumulation
      responses of cell populations representing successive stages of T-cell
      development, namely: immature TcR- thymocytes from SCID mice, proliferating
      cortical blasts, small cortical thymocytes, medullary thymocytes and peripheral T
      cells. We find that all classes of thymocytes exhibit higher cAMP synthesis in
      response to forskolin than peripheral T cells. In immature TcR- thymocytes, this
      high capacity is buffered by efficient phosphodiesterase activity, but in
      CD4+CD8+TcRlow thymocytes, phosphodiesterase activity becomes much less
      effective. Phosphodiesterase activity then rises again after positive selection.
      The ability of thymocytes to respond to prostaglandin E is regulated distinctly
      from their ability to respond to forskolin. Unlike forskolin, PGE1 induces cAMP
      synthesis to similar levels in all classes of thymocytes, possibly due to partial
      activation of phosphodiesterase in cortical thymocytes by PGE1. Finally, we
      report a novel effect of Ca2+/protein kinase C signaling on cAMP accumulation,
      which occurs selectively in the proliferating cortical blasts.

PMID- 8525508
TI  - Expansion of memory Th2 cells over Th1 cells in neonatal primed mice.
AB  - BALB/c mice primed with CAF1 splenocytes during the neonatal stage developed A/J
      specific tolerance with prolonged survival (> 60 days) of A/J skin grafts. Mice
      failed to develop A/J-specific cytotoxicity, but rejected third-party skin grafts
      and generated appropriate third-party cytotoxic T cell responses. We demonstrated
      previously that graft acceptance was associated with enhanced interleukin (IL)-4
      and diminished interferon [IFN]-gamma tolerogen-specific cytokine production,
      whereas third-party graft rejection was associated with the opposite pattern of
      cytokine production. We now report that neonatal mice do not mount mixed
      lymphocyte reaction responses against A/J, but the mice contain a higher
      percentage of IL-4-producing cells that were characterized as CD4+Mel-14lo cells.
      Although alloantigen priming of both neonatal and adult control mice expands the
      CD4+Mel-14lo subset, CD4+Mel-14lo cells from neonatal primed mice produce
      significantly higher levels of IL-4 and IL-10 and lower IFN-gamma, whereas
      CD4+Mel-14lo cells from adult primed mice produce mainly IFN-gamma. Moreover,
      enzyme-linked spot immunosorption analysis demonstrates that, compared with adult
      primed mice, neonatal primed mice contain more IL-4-producing CD4 cells and less
      IFN-gamma-producing cells, which indicates that neonatal antigen exposure induces
      and expands alloreactive Th2 memory CD4 cells. The addition of neutralizing
      antibodies against IL-4 and IL-10 to primary MLR failed to recover IFN-gamma by
      CD4+Mel-14lo cells, but cells secreted IFN-gamma after a second in vitro
      restimulation with tolerogen, which indicates that CD4 cells from neonatal
      tolerant mice have the capacity to differentiate into Th1 cells. In summary,
      neonatal tolerant mice contain higher ratios of Th2/Th1 CD4 cells, and the Th2
      cytokines function to maintain the ratio by inhibiting Th1 differentiation.

PMID- 8525509
TI  - Complement inhibition with an anti-C5 monoclonal antibody prevents acute cardiac
      tissue injury in an ex vivo model of pig-to-human xenotransplantation.
AB  - Prevention of hyperacute xenograft rejection in the pig-to-primate combination
      has been accomplished by removal of natural antibodies, complement depletion with
      cobra venom factor, or prevention of C3 activation with the soluble complement
      inhibitor sCR1. Although these strategies effectively prevent hyperacute
      rejection, they do not address the relative contribution of early (C3a, C3b)
      versus late (C5a, C5b-9) activated complement components to xenogeneic organ
      damage. To better understand the role of the terminal complement components (C5a,
      C5b-9) in hyperacute rejection, an anti-human C5 mAb was developed and tested in
      an ex vivo model of cardiac xenograft rejection. In vitro studies demonstrated
      that the anti-C5 mAb effectively blocked C5 cleavage in a dose-dependent manner
      that resulted in complete inhibition of both C5a and C5b-9 generation. Addition
      of anti-C5 mAb to human blood used to perfuse a porcine heart prolonged normal
      sinus cardiac rhythm from a mean time of 25.2 min in hearts perfused with
      unmodified blood to 79,296, or > 360 min when anti-C5 mAb was added to the blood
      at 50 micrograms/ml, 100 micrograms/ml, or 200 micrograms/ml, respectively. In
      these experiments, activation of the classical complement pathway was completely
      inhibited. Hearts perfused with blood containing the highest concentration of
      anti-C5 mAb had no histologic evidence of hyperacute rejection and no deposition
      of C5b-9. These experiments suggest that the activated terminal complement
      components C5a and C5b-9, but not C3a or C3b, play a major role in tissue damage
      in this porcine-to-human model of hyperacute rejection. They also suggest that
      targeted inhibition of terminal complement activation by anti-C5 mAbs may be
      useful in clinical xenotransplantation.

PMID- 8525510
TI  - Inhibition of the pig to human xenograft reaction, using soluble Gal alpha 1-3Gal
      and Gal alpha 1-3Gal beta 1-4GlcNAc.
AB  - Natural anti-carbohydrate antibodies are central to hyperacute rejection in ABO
      incompatible allotransplantation and in discordant xenotransplantation. ABO
      incompatible rejection has been inhibited successfully using intravenous soluble
      carbohydrates as antibody inhibitors. The approach has been less successful
      previously in pig to primate xenotransplantation, where the necessary
      concentrations of a partial inhibitor (Gal alpha 1-6Glc) proved highly toxic. In
      this study, we have identified more effective inhibitors of the dominant human
      anti-pig antibodies that bind to the pentasaccharide Gal alpha 1-3Gal beta 1
      4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-. The inhibitors are the terminal
      disaccharide (Gal alpha 1-3Gal) and terminal trisaccharide (Gal alpha 1-3Gal beta
      1-4GlcNAc) of the target pentasaccharide. Twelve sera (3 from each ABO blood
      group) were tested in 3 different assays: lymphocytotoxic, lymphocyte flow
      cytometry, and solid-phase antigen ELISA. Fifty percent to 75% inhibition of
      human IgG and IgM was achieved using the disaccharide and trisaccharide
      inhibitors in the range of 10-50 mM. Disaccharide (70 mM) was used to inhibit
      hyperacute thrombosis in pig kidneys perfused for 40 min with heparinized human
      AB whole blood. The disaccharide completely inhibited red cell occlusion of
      glomerular but not of intertubular capillaries, although there was residual
      platelet thrombus in glomeruli. Disaccharide and trisaccharide can, therefore, be
      used in concentrations shown for other carbohydrate inhibitors to be nontoxic,
      for inhibition of hyperacute pig-to-human xenograft rejection. The inhibition is
      incomplete, however, and other antigen specificities and other rejection
      mechanisms are likely to be involved.

PMID- 8525511
TI  - Simultaneous transplantation and intrathymic tolerance induction. A method with
      clinical potential.
AB  - It has been shown that donor-specific tolerance to cardiac allografts can be
      induced by pretreating the prospective recipient with injections of donor
      splenocytes (intrathymically) and antilymphocyte serum (intraperitoneally) weeks
      or days before the actual transplantation. This procedure, however, lacks
      clinical relevance in the case of cadaver donors due to the obligatory interval
      between the start of the tolerance induction protocol and transplantation. We
      have tried to devise a protocol in which this interval is eliminated, thus
      allowing allotransplantation simultaneously with tolerance induction. Our results
      show that simultaneous cardiac allotransplantation and intrathymic tolerance
      induction by intrathymic injection of donor splenocytes and treatment with
      antilymphocyte serum is indeed possible in the PVG to AO high-responder rat
      strain combination, provided that low doses of cyclosporine are given
      intramuscularly on day 1, 2, and 3 after transplantation. As we now are able to
      combine the start of tolerance induction with the actual allotransplantation,
      this procedure may indeed have clinical potential.

PMID- 8525512
TI  - Enhancement of nonspecific resistance by liposome-encapsulated immunomodulators
      does not affect skin graft rejection in mice.
AB  - Administration of liposome-encapsulated immunomodulating agents muramyl
      tripeptide phosphatidyl ethanolamine (LE-MTPPE) or interferon-gamma (LE-IFN
      gamma), or co-encapsulated MTPPE and IFN-gamma (LE-(MTPPE/IFN-gamma)) resulted in
      a dramatic increase of the nonspecific antimicrobial resistance in mice, as shown
      before. This kind of treatment is especially of use in immunocompromised hosts
      who are prone to severe infections. Application of these immunomodulators might
      protect these patients, e.g., transplant recipients, from opportunistic
      infections. However, accelerated rejection of the graft, resulting from
      augmentation of the antimicrobial defense in a nonspecific way, has to be
      avoided. In this study, the effect of treatment with LE-MT-PPE, LE-IFN-gamma, or
      LE-(MTPPE/IFN-gamma) on skin graft rejection in mice was investigated. It was
      found that prophylactic treatment of skin-grafted mice with immunomodulating
      formulations did not influence rejection of the graft. Moreover, in T cell
      depleted mice, which showed a prolonged graft survival compared with
      immunocompetent recipients, the administration of immunomodulators did not change
      the survival time of the grafts compared with T cell-depleted mice that did not
      receive immunomodulators. The results clearly show that, in this experimental
      setting, application of the antimicrobial resistance-enhancing formulations (LE
      MTPPE, LE-IFN-gamma, and LE-(MTPPE/IFN-gamma)) is allowed in graft-bearing
      recipients, without influencing graft survival.

PMID- 8525513
TI  - Histopathological concordance of paired renal allograft biopsy cores. Effect on
      the diagnosis and management of acute rejection.
AB  - To assess the effect of sampling error on renal allograft biopsies, we determined
      the concordance of diagnoses between 2 biopsy samples from the same renal
      allograft and the frequency with which 1 biopsy sample would underdiagnose or
      lead to the undertreatment of acute rejection. Two core samples from the same
      allograft biopsy procedure were labeled as core A and core B and presented to
      both unblinded and blinded pathologists, and each pathologist independently
      assigned an acute and a chronic rejection grade. A set of clinical data with
      pertinent prebiopsy information was combined with either the core A or core B
      histopathological diagnosis and presented to 3 transplant nephrologists who made
      treatment recommendations for each combination. Two cores were obtained in 79
      allograft biopsies. Core pairs differed by > or = 1 grade of acute rejection in
      30% and 50% of cases for unblinded and blinded pathologist readings,
      respectively. Moderate or severe acute rejection would have been missed with a 1
      core in 9.5% of cases, increasing to 25.6% if only biopsy pairs containing at
      least 1 reading of moderate or severe acute rejection are included. Therapy would
      have failed to be increased with a single core in 7.5% of cases, increasing to
      10.5% if only pairs containing at least one recommendation of an increase in
      therapy are included. The use of 2 cores of renal allograft tissue provides
      better diagnostic information and thereby leads to appropriate increases in
      antirejection therapy without increasing the complication rate of the procedure.

PMID- 8525514
TI  - Efficacy of rejection prophylaxis with OKT3 in renal transplantation.
      Collaborative Transplant Study.
AB  - The results of renal cadaver transplants performed between 1984 and 1994 and
      reported to the Collaborative Transplant Study were analyzed to examine the
      effect of rejection prophylaxis with OKT3. OKT3 prophylaxis with sequential
      (i.e., delayed) addition of cyclosporine (CsA), compared with immunosuppressive
      treatment that included CsA but not OKT3, resulted in a significantly higher
      overall 3-year graft survival rate in recipients of first transplants (75 +/- 1%
      vs. 71 +/- 1%, respectively; P < 0.0001) and in recipients of retransplants (68
      +/- 2% vs. 62 +/- 1%, respectively; P < 0.001). In contrast, the simultaneous
      administration of OKT3 and CsA from the first posttransplant day did not result
      in improved graft survival over treatment with CsA alone. Graft survival rates
      were significantly associated with matching for HLA-A, -B, and -DR antigens in
      both first and retransplant recipients treated with a sequential protocol of
      OKT3/CsA (P < 0.01). Among patients with preformed panel reactive lymphocytotoxic
      antibodies > 50%, significantly better 3-year graft survival rates were obtained
      with sequential OKT3/CsA than were achieved without OKT3 in first transplant
      recipients (80 +/- 5% vs. 63 +/- 1%, respectively; P < 0.001) and in retransplant
      recipients (73 +/- 5% vs. 58 +/- 1%, respectively; P < 0.01). Significantly
      improved 3-year graft survival rates with OKT3 and sequential CsA were likewise
      obtained in two other groups of high-risk patients: black recipients (P < 0.001)
      and pediatric recipients (P < 0.01). The results demonstrate an advantage for
      OKT3 prophylaxis in conjunction with delayed CsA therapy among renal transplant
      recipients at high immunological risk, particularly among presensitized patients.

PMID- 8525515
TI  - Does high-dose intravenous immune globulin treatment after bone marrow
      transplantation increase mortality in veno-occlusive disease of the liver?
AB  - Forty-five recipients of bone marrow from HLA-identical siblings were given
      intravenous immune globulin (IVIG) 0.5 g/kg once a week during the first 3 months
      after transplantation. Fifty-three consecutive previously transplanted HLA
      identical siblings were included as controls. Only patients who were
      cytomegalovirus (CMV) seropositive or had a CMV-seropositive donor were included.
      There were no major differences in patient characteristics between the two
      groups. However, more patients in the IVIG group received individualized graft
      versus-host disease (GVHD) prophylaxis with less cyclosporine (P < 0.01), more
      controls received liposomal amphotericin B (P = 0.01), and more patients in the
      IVIG group received low-dose heparin as prophylaxis against veno-occlusive
      disease of the liver (P < 0.001). Median follow-up was 21 months in the IVIG
      group and 47 months in the control group. There were no differences between the
      groups with regard to time to engraftment, hospitalization time, or days with
      fever. No differences between the IVIG group and control group were detected in
      the incidence of acute GVHD grade II-IV (17% vs. 23%) or chronic GVHD (30% vs.
      42%). The incidence of bacterial septicemias (53% vs. 63%) and invasive fungal
      infections (9% vs. 6%) was unaffected by IVIG treatment. The incidence of
      symptomatic CMV infection was the same in the two groups (14% vs. 16%). One
      control patient died of CMV interstitial pneumonitis, and 1 patient from each
      group died from viral interstitial pneumonitis of other origin. The incidence of
      veno-occlusive disease (VOD) was 16% in the IVIG group versus 6% in the controls
      (P = NS). Fatal VOD occurred in 11% of the IVIG group compared with none of the
      controls (P = 0.02). Other transplant-related complications did not differ
      between the two groups. Two-year survival was 62% in the IVIG group and 60% in
      the controls (P = NS). No significant beneficial effect was seen with IVIG, which
      may increase mortality in VOD. The use of high dose IVIG as prophylaxis in marrow
      transplant recipients is questioned.

PMID- 8525516
TI  - Oral beclomethasone dipropionate for treatment of human intestinal graft-versus
      host disease.
AB  - Intestinal graft-versus-host disease (GVHD) causes anorexia, vomiting, abdominal
      pain, and diarrhea. We investigated oral beclomethasone dipropionate (BDP), a
      potent, topically active corticosteroid, as therapy for this disease. Forty-two
      allogeneic marrow-graft recipients with biopsy-proven intestinal graft-versus
      host disease of mild-to-moderate severity received BDP (8 mg daily) for up to 28
      days. Weekly symptom scores, oral intake, and surveillance throat and stool
      cultures were compared with baseline values. Adrenal testing was performed
      serially in patients not receiving concurrent prednisone. Improvement was seen in
      appetite (P < 0.001), oral intake (P < 0.001), nausea (P = 0.013), and diarrhea
      (P = 0.02) over the course of therapy, and an overall beneficial response was
      observed in 72% of 40 evaluable patients. Surveillance cultures of throat and
      stool showed no increase in bacterial or fungal colonization over time. The
      adrenal axis became suppressed in 11 of 20 evaluable patients (55%) but
      suppression was not a prerequisite for clinical response, as 6 of 9 patients who
      retained normal adrenal function improved clinically. We conclude that oral BDP
      is a safe and effective treatment for mild-to-moderate intestinal graft-versus
      host disease. Systemic absorption probably occurs, but adrenal suppression is not
      a prerequisite for clinical efficacy, suggesting that the biological effect is
      primarily topical. BDP should be further investigated as a topical therapy for
      intestinal GVHD.

PMID- 8525517
TI  - Nitric oxide formation as predictive parameter for acute graft-versus-host
      disease after human allogeneic bone marrow transplantation.
AB  - Due to the accumulation of evidence concerning a putative role of nitric oxide
      (NO) in graft-versus-host disease (GVHD), we performed follow-up measurements of
      the stable end-products of NO, nitrite/nitrate (NO2-/NO3-) in plasma of patients
      undergoing allogeneic (n = 16) and autologous (n = 6, as a control) bone marrow
      transplantation. NO2-/NO3- concentrations were set in relation to the clinical
      course and to serum levels of soluble tumor necrosis factor receptor 75 (sT-NFrec
      75) and neopterin, both of which are known to be sensitive indicators of cellular
      immune activation phenomena involving macrophages in vivo, and endogenous
      interleukin (IL)-10, a major T helper cell type 2 (TH-2)-derived cytokine and
      potent inhibitor of macrophage activation and NO formation. A significant rise of
      NO2-/NO3- levels was observed in patients with GVHD and preceded the onset of
      clinical symptoms by up to 3 days. In contrast to indicators of macrophage
      activation, i.e., neopterin and sT-NFrec75, NO2-/NO3- concentrations were not
      significantly altered from baseline levels during infectious complications, as
      NO2-/NO3- concentrations did not fluctuate in patients after autologous
      engraftment. During episodes of acute GVHD, NO2-/NO3- concentrations showed a
      strong positive correlation with levels of plasma neopterin and sTNFrec 75, but
      were also significantly related to IL-10. In non-GVHD patients, a negative
      correlation between IL-10 and NO2-/NO3- concentrations was evident. Therefore,
      NO2-/NO3- determination may be a valuable early indicator of the initiation of
      human GVHD. Our results provide some further insights concerning cytokine-related
      metabolic changes in the course of human GVHD in vivo which may prove useful in
      the development of new therapeutic approaches for this disease.

PMID- 8525518
TI  - Anemia and erythropoietin levels in lung transplant recipients.
AB  - An evaluation of 26 surviving outpatient lung transplant recipients at one center
      showed that 65% (17/26) had significant anemia (hemoglobin < 11 g/L for women, <
      14 g/dl for men) at a median follow-up of 13.5 months after transplantation
      (range, 1-41 months). There were 14 men and 12 women with a mean age of 45.1
      years (range, 23.1-66.7 years). Fifteen had a double allograft and 11 had a
      single allograft. Anemia was normochromic and normocytic/macrocytic with a
      tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency
      (transferrin saturation < 20%) was found in 35% (6/17) of anemic patients, and
      two of them also had ferritin levels < 15 micrograms/L. In addition, vitamin B12
      was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels
      were significantly decreased in anemic lung transplant recipients as compared
      with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1-41
      mU/ml, vs. 53 mU/ml, 15-88 mU/ml; P < 0.05). In nonanemic lung transplant
      recipients, erythropoietin levels were decreased too, as compared with normal
      controls (median, 2 mU/ml, range 1-21 mU/ml, vs. 5 mU/ml, 3-32 mU/ml; P < 0.05).
      Investigation of peripheral stem cells in 9 patients showed normal stimulation of
      erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128-1898
      cells/ml) independent of erythropoietin concentrations. Analysis of putative
      prognostic factors, such as age, surgical procedure (double vs. single lung
      allograft), indication for transplantation, time after transplantation, infection
      status, presence of bronchiolitis obliterans, immunosuppression (+/-
      azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial
      partial pressure of oxygen, did not demonstrate any difference in erythropoietin
      concentrations. Only the sex variable revealed a trend to higher levels in women
      than in men (median, 4 mU/ml, range 1-41 mU/ml, vs. 1 mU/ml, 1-16 mU/ml; P >
      0.05). The causes for low erythropoietin levels are not quite understood yet;
      however, they offer a rationale for the treatment of chronic anemia with
      recombinant human erythropoietin.

PMID- 8525519
TI  - Late acute failure of well-HLA-matched renal allografts with capillary congestion
      and arteriolar thrombi.
AB  - Seventeen cases of a histologically and clinically unusual renal acute
      dysfunction in kidney recipients, individualized among a population of 1378, are
      reported. The basic histological lesion was a huge capillary congestion,
      associated with capillary and arteriolar thromboses or parenchymal necrosis in
      most patients, and contrasting with the absence of the classical features of
      acute cellular rejection, i.e., tubulitis, glomerulitis, edema, and infiltrate.
      The corresponding clinical history was characterized by its early timing in the
      course of transplantation (< 3 months), its sudden occurrence in patients usually
      having good transplant function, leading to end-stage renal failure in a few
      days, and its resolution under rejection treatment. The occurrence of this
      syndrome was significantly linked with a good HLA matching: 13 of the 17
      recipients were HLA-DR matched (P < 0.0001). The etiology of this syndrome
      remains unknown. There was no evidence for graft vessel thrombosis. Because of
      some histological similarities, the usual causes of the hemolytic uremic
      syndrome, including bacterial and viral infections or cyclosporine
      arteriolopathy, were discussed. Acute vascular rejection was suspected, but the
      cross-match was negative on T lymphocytes in all cases and anti-HLA class I and
      II antibodies were not found to develop at the time of transplant dysfunction,
      except in 1 patient, in whom the detected anti-DR antibodies were not directed at
      the kidney donor. Anti-human umbilical vein endothelial cell antibodies, detected
      in an antibody-dependent cellular cytotoxicity assay, were present in 6 patients
      (of the 14 tested) at the onset of renal failure, but they were either absent (n
      = 3) or already present at the time of transplantation (n = 5) in the other 8
      patients. Therefore, reliable arguments are lacking to conclude that this acute
      transplant dysfunction is an acute vascular rejection and its strong association
      with HLA matching has, as yet, no satisfactory explanation.

PMID- 8525520
TI  - CD4 Th2 cells do not functionally suppress CTL generation in neonatal tolerant
      mice.
AB  - Injecting semiallogeneic CAF1 spleen into BALB/c newborn mice renders mice
      tolerant, and the majority of mice show prolonged survival of tolerogen-bearing
      A/J skin grafts. Moreover, graft survival is associated with enhanced Th2
      cytokine responses and graft rejection with Th1 cytokine responses. To further
      delineate the mechanisms of tolerance, we evaluated CTL responses and found that
      74% of neonatal primed mice failed to generate A/J-specific CTL responses, as
      determined by standard CTL assays and pTc3 frequency analyses. CTL
      unresponsiveness coexisted with an enhanced tolerogen-specific Th2 memory
      cytokine profile; spleen cells from neonatal primed mice secreted more
      interleukin (IL)-4 and less IL-2 and interferon (IFN)-gamma in MLR cultures
      compared with either adult primed or naive controls. We therefore examined the
      hypothesis that enhanced Th2 cytokine levels prevent the generation of tolerogen
      specific CTL. Adding neutralizing antibodies to IL-4 and IL-10 recovered IFN
      gamma production in vitro but not A/J-specific CTL response. In addition, CD4
      cells from neonatal primed mice provided help for primary or secondary CD8 CTL
      generation, which suggests that the enhanced Th2 cytokine profile does not
      actively suppress CTL generation. Furthermore, CD4 cells from adult primed mice
      failed to restore the A/J-specific CD8 CTL generation of neonatal primed mice.
      The results show that failure to develop A/J-specific CTL reaction occurs without
      suppression by the enhanced Th2-type responses and imply that either deletion or
      anergy mechanisms block CTL generation. Therefore, neonatal alloantigen exposure
      not only shifts the development of alloreactive CD4 cells toward Th2, but also
      blocks development of alloreactive CD8 CTL in this strain combination.

PMID- 8525521
TI  - Induction of tolerance to skin allografts by intrathymic injection of donor
      splenocytes. Effect of donor-recipient strain combination and supplemental
      rapamycin.
AB  - The effect of donor-recipient strain combination and supplemental rapamycin
      (Rapa) on tolerance induction by intrathymic (IT) injection of donor splenocytes
      was examined in a mouse skin allograft model. In an MHC class I-mismatched C3H/He
      skin to (C57BL/6 x A)F1 (B6AF1) mouse combination, IT injection of 50 x 10(6)
      donor splenocytes with transient immunosuppression by rabbit anti-mouse
      lymphocyte serum (ALS) induced significant prolongation of skin allograft
      survival with a median survival time (MST) of 115 days versus an MST of 24.5 days
      in controls given ALS alone. With an additional short course of supplemental Rapa
      treatment at a dose of 1.5 mg/kg i.p. every other day from day 0 to 12, all
      C3H/He skin allografts survived indefinitely (> 350 days) in ALS-treated, donor
      splenocyte intrathymically injected B6AF1 recipient mice. Tolerance was antigen
      specific, since the second donor-type skin allografts were accepted while third
      party skin allografts were acutely rejected in these mice bearing long-term
      C3H/He skin allografts. In MHC class I- and II-disparate (DBA/2 to B6AF1) and
      fully MHC-incompatible (AKR to B6) strain combinations, IT injection of donor
      splenocytes and ALS treatment failed to prolong skin allograft survival over ALS
      controls. When supplemental Rapa was used, long-term skin allograft acceptance
      was observed with an MST of 127 days for the DBA/2 to B6AF1 combination and 70
      days for the AKR to B6 combination. In contrast, supplemental treatment with
      cyclosporine was not effective in these combinations, which suggests that
      supplemental Rapa may have a unique effect in augmenting IT tolerance induction.
      Thymectomy within 7 days after IT injection significantly shortened the allograft
      survival, which suggests that interaction of the host thymus and the injected
      donor splenocytes, which takes place early after IT injection, plays an important
      role in the induction of allograft tolerance in this model.

PMID- 8525522
TI  - Characterization of human IgG-binding xenoantigens expressed by porcine aortic
      endothelial cells.
AB  - Xenoreactive antibodies (XAb) play a major role in the rejection of xenografts.
      In this study, human IgG XAb that bind to xenoantigens expressed by porcine
      aortic endothelial cells (PAEC) were characterized, together with their
      corresponding xenoantigens. Using an ELISA with both fixed and unfixed confluent
      monolayers of PAEC, XAb of both IgG and IgM classes in pooled and individual
      normal human serum were identified. The binding of these IgG XAb to the
      endothelium is mediated by F(ab')2 and the only detectable subclasses that bind
      to the endothelium are IgG1 and IgG2. On the basis of direct binding experiments,
      inhibition and antibody adsorption studies, and enzymatic digestions, it is shown
      that only a minor component of the XAb binding is directed against galactose in
      an alpha 1,3 linkage with galactose on PAEC surfaces. There is some cross
      reactivity with antigens expressed on porcine lymphocytes, but not porcine red
      blood cells. Histological examination of sections of porcine aortae, snap-frozen
      and stained using immunoperoxidase techniques, confirmed interaction with the
      vascular endothelium. Labeling of the PAEC with 125I, followed by cell lysis and
      immunoprecipitation under reducing conditions, showed binding of IgG XAb to
      several components on the endothelial cell surface, the most prominent of which
      have apparent molecular masses of 75 kDa, 110 kDa, 180 kDa, and 210 kDa. The 110
      kDa component and the 180-kDa component were sensitive to digestion with
      endoglycosidase F, which suggests the participation of N-linked carbohydrate
      structures. These studies demonstrate that human IgG XAb recognize multiple
      determinants expressed by PAEC, a minor population of which contain alpha 1,3
      linked galactose residues. Cross-reactive determinants are expressed on porcine
      lymphocytes but not porcine red blood cells.

PMID- 8525523
TI  - Monoclonal antibodies directed against human C5 and C8 block complement-mediated
      damage of xenogeneic cells and organs.
AB  - The hyperacute rejection (HAR) of xenotransplanted organs is initiated by the
      deposition of natural antibodies on donor endothelium followed by the activation
      of the recipient complement system, which rapidly destroys the graft. Studies of
      the role of activated complement in HAR have suggested that natural antibody as
      well as early (C3a, C3b) and late (C5a, C5b-9) activated complement components
      may contribute to cell activation and damage. Attenuation of HAR has been
      achieved by blockade of C3 activation with soluble CR1 or consumptive depletion
      of complement with cobra venom factor; however, similar studies using specific
      inhibitors of terminal complement components have not been described. To address
      the contribution of C5a and the membrane attack complex (C5b-9, MAC) to
      complement-mediated xenogeneic cell and organ damage, we utilized functionally
      blocking monoclonal antibodies directed against the human terminal complement
      components C5 and C8. Our data show that both anti-C5 and anti-C8 mAbs protect
      porcine aortic endothelial cells from membrane damage mediated by human C5b-9.
      Additionally, both the anti-C5 and anti-C8 mAbs blocked complement-mediated
      generation of membrane prothrombinase activity on porcine aortic endothelial
      cells challenged with human serum. To test the ability of these antibodies to
      attenuate antibody and complement-mediated damage of xenogeneic organs, an ex
      vivo model was developed wherein isolated rat hearts were perfused with human
      serum in the presence or absence of the anti-C5 and anti-C8 mAbs. Our data
      demonstrate that mAbs directed against human C5 and C8 prevented organ damage by
      human serum complement and suggest that these molecules may serve as potent
      inhibitors of HAR.

PMID- 8525524
TI  - Increased levels of soluble interleukin-2 receptor in veno-occlusive disease of
      the liver after allogenic bone marrow transplantation.
AB  - Serum levels of soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor
      (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 were studied in
      patients who developed veno-occlusive disease of the liver (VOD) after allogenic
      bone marrow transplantation (BMT). sIL-2R increased by a mean of 366% in 10 VOD
      patients. This was significantly higher than in control patients (n = 12)
      undergoing BMT without major complications (103%, P = 0.002) or in patients (n =
      10) with grade II or III acute graft-versus-host disease (aGVHD) (139%, P =
      0.003). Peak sIL-2R levels occurred on day 17 +/- 4 (mean +/- SD) after BMT in
      VOD patients versus on day 29 +/- 11 in patients with grades II-III aGVHD (P =
      0.006). Mean maximum sIL-2R values in VOD patients were 4548 +/- 1420 (+/- SD,
      U/ml), which was significantly higher than the value of 2123 +/- 1023 U/ml in
      control patients undergoing BMT without major complications (P < 0.001). In
      patients with grade II or III aGVHD, mean maximum sIL-2R levels were 3076 +/-
      2264 U/ml. Serum levels of TNF-alpha, IFN-gamma, and IL-6 were also increased
      during VOD and aGVHD, with peak levels occurring at the same time as peak sIL-2R
      levels in most patients. We found no difference in peak levels between VOD and
      acute GVHD patients. To conclude, an early dramatic increase in sIL-2R was seen
      in patients with VOD. Inflammatory cytokines like IL-6, TNF-alpha, and IFN-gamma
      also increased during VOD and aGVHD.

PMID- 8525525
TI  - Porcine vascular cell adhesion molecule (VCAM) mediates endothelial cell adhesion
      to human T cells. Development of blocking antibodies specific for porcine VCAM.
AB  - Vascular cell adhesion molecule (VCAM) is expressed on activated endothelial
      cells and binds to the alpha 4 beta 1 integrin receptor, very late antigen-4 (VLA
      4), expressed on human lymphoid cells. Anti-VCAM mAbs have been shown to prolong
      allograft survival. To explore the role of porcine VCAM (pVCAM) in
      xenotransplantation, a recombinant secreted form of pVCAM (spVCAM) was expressed
      in 293-EBNA cells and purified by metal affinity chromatography. A human lymphoid
      cell line bound to spVCAM in a VLA-4-dependent manner. Using spVCAM as an
      immunogen, we developed three anti-pVCAM mAbs that reacted with cell surface
      pVCAM on porcine aortic endothelial cells (PAEC) but not to human VCAM on human
      umbilical vein endothelial cells. Pairwise interaction analysis indicated that
      these mAbs recognized distinct epitopes on pVCAM. Two anti-pVCAM mAbs, 2A2 and
      3F4, inhibited the binding of Ramos cells to spVCAM, while the third, 5D11, did
      not. Similarly, mAbs 2A2 and 3F4 inhibited binding of Ramos cells or human
      peripheral blood T cells to activated PAEC. The extent of inhibition with mAbs
      2A2 and 3F4 was comparable to the inhibition obtained with a blocking mAb to
      human VLA-4. These anti-pVCAM mAbs will provide a means to specifically block
      pVCAM in a xenograft setting and allow the determination of the role of pVCAM in
      a primary xenogeneic immune response.

PMID- 8525526
TI  - The SCID mouse reaction to human peripheral blood mononuclear leukocyte
      engraftment. Neutrophil recruitment induced expression of a wide spectrum of
      murine cytokines and mouse leukopoiesis, including thymic differentiation.
AB  - In this study, we describe the kinetics of host immune reactions occurring in
      mice with severe combined immunodeficiency (SCID) at different times after the
      intraperitoneal injection of human peripheral blood mononuclear leukocytes
      (huPBL). At 24 hr, a massive neutrophil recruitment and an induced expression of
      a wide spectrum of murine cytokine mRNA (i.e., interleukin [IL]-1 beta, IL-4, IL
      6, IL-10, IL-12, tumor necrosis factor [TNF]-alpha and interferon [IFN]-gamma)
      occurred in the huPBL-SCID mouse peritoneal cavity. By using ELISAs specific for
      mouse cytokines, large amounts of IL-1-alpha, TNF-alpha, IL-6, and IFN-gamma were
      detected in the peritoneal washings of huPBL-SCID mice 1 day after
      intraperitoneal injection. IL-6 and IFN-gamma production persisted for up to 2
      weeks after PBL transplantation. Medullary and extramedullary expansion of the
      SCID mouse hematopoietic cells also occurred in the chimeras as early as 1 week
      after injection, together with a marked thymic differentiation (murine CD4+/CD8+
      cells) at 10-12 weeks after transplantation. On the whole, these results indicate
      that, after huPBL injection, SCID mice mount a complex multistage immune
      response. These host reactions should be taken into consideration for any
      accurate interpretation of results obtained using the huPBL-SCID model. The
      control of responses (by means of specific antibodies to murine cytokines and to
      granulocytes or through the use of anti-inflammatory drugs) may be helpful in
      improving the engraftment of huPBL in SCID mice and in furthering our knowledge
      of the T and B cell-independent natural immune reactions.

PMID- 8525527
TI  - Evolution of glomerular basement membrane changes in chronic rejection.
AB  - We have investigated the evolution of chronic glomerular changes in the absence
      of the recurrence of original disease in an experimental rat model of chronic
      renal allograft rejection. Using serial graft needle biopsies and serum
      creatinine levels, we were able to focus on early glomerular changes that are
      associated with good graft function. The recipient rats were divided into 5
      groups, 2 with allogeneic (DA to WF) transplants and 3 with syngeneic (DA to DA)
      transplants. In the first 2 allogeneic groups, one group received cyclosporine
      (CsA) for 2 weeks (n = 7) and the other received CsA for 12 weeks (n = 5). In the
      2-week treatment group, all allografts developed chronic rejection, compared with
      none in the 12-week group. Syngeneic controls received CsA for 2 (n = 3) and 12
      weeks (n = 3), or no immunosuppression (n = 2) in order to exclude the effects of
      CsA. The first detectable ultrastructural event was slight deposition of electron
      lucent material in the glomerular basement membrane. Contrary to previous
      morphological studies, the initial deposition was not subendothelial, but was
      within the lamina densa itself. Examination of allogeneic grafts with good graft
      function and syngeneic grafts showed glomerular alterations that were similar to
      the early changes preceding chronic rejection. The intensity of changes in
      optimally immunosuppressed allografts was mild, and they were arrested early in
      the evolving stage of glomerular basement membrane changes. In the suboptimally
      immunosuppressed allografts with chronic rejection, the glomerular basement
      membrane changes became more pronounced and extensive in subsequent biopsies.
      Thus, all recipients in different groups showed similar glomerular alterations,
      but to different intensities. These results suggest a common pathogenetic
      mechanism which might be endothelial damage. In chronic rejection, the
      endothelial damage might be immunologically mediated by rejection episodes and
      progressive, whereas in syngeneic grafts and in allografts without chronic
      rejection, perioperative trauma, ischemia, and graft reperfusion may be
      responsible for the self-limiting glomerular changes.

PMID- 8525528
TI  - Light and electron microscopic observations of epithelial shedding in stored
      canine small intestine.
AB  - Simple cold storage of canine small intestine is accompanied by ischemic damage
      to the intestinal mucosa. Progression of damage observed during cold storage is
      unique and has not been observed with other organs. The mucosal damage begins
      within 15 min after the onset of the storage, with progressive involvement of the
      gut as the storage period lengthens. Cytoplasmic blebs develop from the base of
      the epithelial cells and detach the epithelium from the basal lamina. While the
      process begins uniformly along the length of the villus, separation of the
      epithelium occurs first at the villus tip. The epithelium, which is shed into the
      intestinal lumen, is otherwise undamaged. Blebbing occurs in enteroendocrine and
      goblet cells and is not restricted to enterocytes. Early blebs occur in proximity
      to mucosal mast cells and subepithelial nerves. Tissue damage in cold is possibly
      related to enzymes that are still active at storage temperatures.

PMID- 8525529
TI  - Recruitment of semiallogeneic dendritic cells to the thymus during post
      cyclosporine thymic regeneration.
AB  - Based on studies of the thymic microenvironment in the model of cyclosporine
      (CsA)-associated syngeneic graft-versus-host disease, we have hypothesized that
      immune tolerance develops after CsA is stopped, as the thymus regenerates and
      recruits new dendritic cells. CsA normally induces medullary involution with
      destruction of the medullary dendritic cells (DC) and epithelium. This principle
      could provide practical advantages for transplantation if it is used to recruit
      new DC into the thymic medulla. Here we administer LEW x BN F1 splenocytes to BN
      rats and treat them with a short course of CsA. After CsA is stopped, the F1
      cells are rapidly recruited to the thymus, and by 10 days after CsA, they are
      localized at the corticomedullary junction, the natural location of thymic DC. In
      contrast, dexamethasone, which induces cortical involution, did not lead to
      thymic recruitment of F1 DC. Recruitment was better if the splenocytes were
      administered before CsA was stopped. Engraftment of the thymus was also achieved
      using bone marrow and temporary skin grafts as sources of DC. These observations
      provide the basis for a novel approach to inducing tolerance to alloantigens with
      minimal immune suppression and define the goals for further development.

PMID- 8525530
TI  - Contrasting in vivo effects on T helper cell functions induced by mitogenic
      (intact) versus nonmitogenic (F(ab')2) anti-CD3 monoclonal antibody.
AB  - Anti-CD3 mAbs are potent inhibitors of T cell function; however, administration
      of mitogenic mAb can cause significant morbidity secondary to T cell activation
      and cytokine release. Nonmitogenic anti-CD3 mAb is immunosuppressive in mice
      without inducing detectable morbidity, and may thus be preferable for in vivo T
      cell immunosuppression. The precise mechanisms of action of these two forms of
      mAb have not been fully defined. To further characterize and compare the in vivo
      functional effects of mitogenic and nonmitogenic anti-CD3 mAbs, mice were treated
      with the intact (mitogenic) form of the anti-murine CD3 mAb, 2C11, or with
      F(ab')2 fragments (nonmitogenic). Effects on T cell phenotypes and the secretion
      of Th1-derived cytokines were compared. Nonmitogenic mAb induced a prolonged
      downregulation of secretion of interleukin (IL)-2 and interferon (IFN)-gamma from
      CD4+ T cells, and of IL-2 secretion from CD8+ T cells, and preferential depletion
      of CD4+ T cells. In marked contrast, mitogenic mAb induced a prolonged
      upregulation of IL-2 and IFN-gamma secretion from both CD4+ and CD8+ cells, and
      preferential depletion of CD8+ T cells. Both forms of mAb induced a shift in the
      T cell populations from a naive to a memory phenotype; however, this shift was
      not responsible for the observed changes in cytokine secretion. These results
      demonstrate that mitogenic and nonmitogenic forms of 2C11, while binding to the
      identical epitope, differentially affect T cell functions, and have implications
      for the use of anti-CD3 mAbs in the clinical setting.

PMID- 8525531
TI  - Interleukin 12 in combination with anti-interleukin 10 reverses graft
      prolongation after portal venous immunization.
AB  - Portal venous pretransplantation transfusion augments allogeneic skin graft
      survival in mice transplanted across multiple minor histocompatibility barriers.
      We have shown in earlier studies that this is correlated with preferential
      activation for production of type-2 cytokines (interleukin [IL]-4 and IL-10) and
      decreased production of type-1 cytokines (IL-2 and interferon-gamma). We show
      that recombinant IL-12, in association with anti-IL-10 monoclonal antibody, can
      reverse in vivo the graft prolongation afforded by portal venous immunization and
      the altered cytokine production that follows. These alterations are in turn
      associated with increased expression of messenger RNA for interferon-gamma, IL-2,
      and IL-12 and decreased expression of IL-4, IL-10, and IL-13, as determined by
      non-quantitative polymerase chain reaction using cells obtained from lymph nodes
      draining the graft. Recombinant IL-12 in vitro also produces dose-related
      inhibition of activation for production of type-2 cytokines.

PMID- 8525532
TI  - Molecular analysis of C3 allotypes related to transplant outcome in human renal
      allografts.
AB  - The third component of complement (C3) exists in two main allotypic forms, C3S
      and C3F, which can be distinguished at the molecular level using a variation of
      the polymerase chain reaction. An increased frequency of the C3F allele has been
      noted in a number of autoimmune and inflammatory conditions affecting the kidney,
      including systemic vasculitis, IgA nephropathy, and type II mesangiocapillary
      nephritis. Recently, in an unrelated study, we found (with small numbers) an
      increased incidence of graft loss associated with the presence of the C3F allele.
      To further assess this, we analyzed the S/F polymorphism in 183 donor-recipient
      pairs of patients undergoing renal transplantation. Forty-one of 183 grafts were
      lost, but graft loss was not associated with the C3F allele over 14-month follow
      up. However, the presence of the C3F allele predicted an increased risk of graft
      dysfunction (defined as serum creatinine > 150 mumol/L): 61/105 versus 36/78,
      with a relative risk of 1.4 (P < 0.05). The C3F allele predisposed toward graft
      dysfunction when present in either donor or recipient. The presence of two C3F
      alleles gave a relative risk for graft dysfunction of 1.8, suggesting a dose
      dependent effect, although numbers were small. The presence of the C3F allele was
      not significantly correlated with the number of rejection episodes, serum
      creatinine, or duration of primary nonfunction. These findings suggest that C3F
      may be a susceptibility allele for allograft injury. Possible mechanisms for this
      association are discussed.

PMID- 8525533
TI  - Effect of rapamycin on renal allograft survival in canine recipients treated with
      antilymphocyte serum, donor bone marrow, and cyclosporine.
AB  - Rapamycin (Rapa) monotherapy can promote renal allograft survival in dogs, but it
      is very toxic. To attempt to augment the effectiveness of Rapa and reduce its
      toxicity in a tolerance induction protocol, canine renal allograft recipients
      were treated briefly with antilymphocyte serum (ALS), donor bone marrow cells
      (BMC), and a limited course of cyclosporine (CsA). Rapa had little effect when
      CsA-treated recipients were given ALS on days -5 to -1 and BMC on day +1. When
      combined with CsA given days +13 to +42, ALS on days -5 to +7, and BMC on day
      +10, Rapa at 0.3 mg/kg on day +8 plus alternate days +15 to +39 significantly
      increased overall survival and was compatible with long-term survival after
      immunosuppression (6 grafts, 1 graft > 212 days, 1 graft > 470 days). Rapa
      appeared to prevent early rejections that can occur during treatment with these
      ALS/BMC/CsA protocols. Little toxicity of Rapa was observed with any treatment.

PMID- 8525534
TI  - Prolongation of survival of guinea pig heart grafts in cobra venom factor-treated
      rats by splenectomy. No additional effect of cyclosporine.

PMID- 8525535
TI  - Renal transplantation one week after conception.
AB  - A successful 38-week pregnancy is reported following renal transplantation
      approximately 1 week after conception. The patient was treated with quadruple
      sequential induction therapy, maintenance immunosuppression, and routine
      posttransplantation care, including ganciclovir treatment for a symptomatic
      cytomegalovirus infection during the pregnancy and 3 months after delivery. No
      decline in renal function was noted. The mother and child remain healthy at 18
      months. This case demonstrates the ability of renal transplant patients to
      maintain renal function throughout pregnancy and the lack of deleterious effects
      upon the child during gestation and at up to 18 months after birth, despite
      significant immunosuppression, including antithymocyte globulin induction
      therapy, and infectious complications of the mother's renal transplantation.

PMID- 8525536
TI  - Variant B human herpesvirus-6 associated febrile dermatosis with thrombocytopenia
      and encephalopathy in a liver transplant recipient.
AB  - Human herpesvirus 6 (HHV-6) is a recently discovered virus the pathogenicity of
      which in solid organ transplant recipients has not been defined. We describe a
      unique febrile syndrome due to disseminated invasive variant B HHV-6 infection in
      a liver transplant recipient with evidence of direct tissue invasion by the
      virus. Acute febrile illness characterized by life-threatening thrombocytopenia,
      progressive encephalopathy and skin rash developed in association with invasive
      HHV-6 infection in a liver transplant recipient. HHV-6 was isolated from the
      patient's peripheral blood in cell culture; variant B HHV-6 DNA was detected in
      the patient's peripheral blood mononuclear cells (PBMC) at a concentration
      greater than 1000 virus genomes per 10(6) PBMC. A bone marrow biopsy was also
      positive for HHV-6, documenting direct tissue invasion. Intravenous ganciclovir
      for three weeks led to a prompt clinical response. Although larger studies are
      warranted, our case suggests that HHV-6 should be considered in the diagnostic
      evaluation of patients with fever, cytopenia, and encephalopathy, particularly
      since HHV-6 is susceptible to ganciclovir and foscarnet.

PMID- 8525537
TI  - Long-term ganciclovir prophylaxis eliminates serious cytomegalovirus disease in
      liver transplant recipients receiving OKT3 therapy for rejection.
AB  - We conducted a trial of long-term ganciclovir prophylaxis for prevention of
      cytomegalovirus (CMV) disease in liver transplant recipients receiving OKT3
      therapy for rejection. Intravenous ganciclovir (6 mg/kg once a day, Monday
      through Friday) was initiated on the same day OKT3 therapy was started and
      continued for 4 or more weeks. Fifty-one consecutive adult patients (80% CMV
      seropositive, 20% CMV seronegative) were evaluated. Due to the patient's
      noncompliance or the primary physician's decision, 6 patients received less than
      2 weeks of ganciclovir. Three of these 6 (50%) developed CMV disease (hepatitis
      1, CMV syndrome 2). In contrast, of 45 patients receiving 4 or more weeks of
      prophylactic ganciclovir, only 1 (2.2%) developed CMV disease (hepatitis). There
      were no cases of CMV disease among 29 patients who received 6 or more weeks of
      ganciclovir. Reversible neutropenia in 2 patients (4.4%) was the only side effect
      associated with long-term ganciclovir. Complications from central intravenous
      catheters did not occur. These results suggest that CMV can be eliminated as a
      significant pathogen in liver transplant recipients receiving OKT3 for rejection
      by the long-term administration of prophylactic gnaciclovir, which is safe.

PMID- 8525538
TI  - Interleukin-12 mRNA levels in renal allograft fine-needle aspirates do not
      correlate with acute transplant rejection.
AB  - TH1 cytokines, including gamma-interferon (IFN), are critical in the initiation
      and progression of allograft rejection. As interleukin (IL)-12 up-regulates gamma
      IFN, we assessed the role of IL-12 in human transplant rejection. Twenty renal
      allograft fine-needle aspirates from 19 patients were obtained, evaluated in the
      standard fashion, and assessed for gamma-IFN and IL-12p40 subunit mRNA levels
      using nested reverse transcriptase polymerase chain reaction. Ten aspirates
      demonstrated acute rejection by clinical criteria, and 9 of the 10 aspirates
      contained gamma-IFN while only 3 demonstrated IL-12; there were no distinguishing
      characteristics for these 3 patients with regard to therapy, or time of onset and
      severity of rejection. Seven patients without clinical or morphologic rejection
      failed to demonstrate gamma-IFN or IL-12. Three patients had discrepant findings;
      there was no morphologic rejection, yet all 3 patients contained gamma-IFN and 1
      patient demonstrated rejection on subsequent biopsy. However, only 1 aspirate
      exhibited IL-12 and this patient had no documented subsequent rejection. This
      study confirms the association of gamma-IFN mRNA with acute rejection. In
      contrast, IL-12 mRNA does not appear to play a key role early in the rejection
      process.

PMID- 8525539
TI  - Magnetic resonance angiography in the evaluation of living-related renal donors.
AB  - Live-donor kidney donation requires an accurate determination of renal arterial
      anatomy. Traditionally, conventional angiography has supplied this information.
      The present study was undertaken to determine the accuracy of magnetic resonance
      angiography (MRA) compared with conventional angiography (CA) in the evaluation
      of potential living renal donors. Fifteen potential living renal donors underwent
      both conventional angiography (midstream aortic injection) and three-dimensional
      phase contrast MRA. Two overlapping volumes of 64 slices (slice thickness 1.5 mm)
      were obtained in the axial plane to allow coverage from the celiac trunk to the
      aortic bifurcation. Conventional angiography demonstrated single renal arteries
      in 24 kidneys and multiple renal arteries in 6 kidneys. Magnetic resonance
      angiography demonstrated multiple renal arteries in 5 of the 6 kidneys. The
      sensitivity of MRA in determining kidneys with multiple renal arteries was 83%
      (5/6). One kidney with an accessory 2-mm polar artery was incorrectly identified
      as having a single renal artery by MRA. The overall accuracy of MRA in
      identifying the number of renal arteries was 97% (29/30). Fibromuscular dysplasia
      was demonstrated in 2 patients by CA, but was not visualized prospectively by
      MRA. Based on standard physician and hospital fees for each procedure, use of MRA
      alone would represent a cost savings of approximately $1900 over CA. Despite its
      minimally invasive and economic attractions, MRA does not achieve the level of
      accuracy required to replace CA in the evaluation of potential living kidney
      donors.

PMID- 8525540
TI  - Granulocyte/macrophage colony-stimulating factor-stimulated hepatic dendritic
      cell progenitors prolong pancreatic islet allograft survival.
AB  - Liver-derived dendritic cell (DC) progenitors propagated in liquid culture in
      granulocyte/macrophage colony-stimulating factor exhibit low levels both of cell
      surface MHC class II antigens and of counter-receptors for CTLA-4/CD28. They fail
      to stimulate allogeneic T cells in mixed leukocyte cultures. To evaluate their in
      vivo functional significance, we determined their influence on survival of
      pancreatic islet allografts. Cultured B10.BR (H2k;I-E+) mouse liver-derived DC
      progenitors were injected (2 x 10(6) i.v.) into streptozotocin-diabetic B10 (H2b;
      I-E-) recipients 7 days before transplantation of pancreatic islets (700
      IEq/mouse) from the same donor strain. No immunosuppressive agents were
      administered. Mean islet allograft survival time was prolonged from 15.3 days (in
      animals pretreated with syngeneic cells) to 30.3 days (P < 0.001) in mice
      pretreated with the donor-derived liver cells. In 20% of these animals, islet
      allograft survival exceeded 60 days. These data suggest that liver-derived DC
      progenitors may contribute both to the inherent tolerogenicity of the mouse liver
      and to its capacity to protect other allografts of the same donor strain from
      rejection.

PMID- 8525541
TI  - Interleukin-1 or tumor necrosis factor-alpha antagonists do not inhibit graft
      versus-host disease induced across the major histocompatibility barrier in mice.
AB  - We show that while interleukin-1 and tumor necrosis factor-alpha antagonists are
      partially able to inhibit graft-versus-host disease (GVHD) when bone marrow (BM)
      transplantation is performed in irradiated recipients of minor antigen-disparate
      donor BM, these same antagonists do not inhibit GVHD when donor BM is fully MHC
      disparate. This failure in MHC-disparate recipients occurs despite the presence
      of interleukin-1 and tumor necrosis factor-alpha mRNA in tissues of GVHD mice
      measured by in situ hybridization and despite escalation of antagonist dosages
      far beyond those used in previous reports. These findings indicate that a
      relationship may exist between cytokines that amplify GVHD and target antigens
      that elicit GVHD. Moreover, when GVHD inhibition was observed in the minor model,
      it was transient, which suggests that it may be important to target more than one
      cytokine to effectively inhibit GVHD. These findings suggest that caution is in
      order in clinical GVHD studies based entirely on anti-proinflammatory cytokine
      treatment.

PMID- 8525542
TI  - Transvenous liver biopsies in marrow transplant recipients.

PMID- 8525543
TI  - What, precisely, is "induction therapy"? A plea to standardize the term.

PMID- 8525544
TI  - Cyclosporine dosing.

PMID- 8525545
TI  - [Cytophotometric, morphometric and electron microscopic studies of the
      cardiomyocytes of the human atrium in ischemic heart disease].
AB  - During an open-heart surgery, right atrium myocytes were obtained from 5 patients
      (aged from 40 to 54 years) with ischemic hearts. The DNA and total protein
      contents were measured in isolated cells using two-wavelength scanning
      cytophotometry after the double staining: the Feulgen nuclear reaction followed
      by naphthol yellow S staining. The degree of ploidy in the investigated myocytes
      appeared not high. The number of 2c, 4c and 8c cells varied, respectively, from
      35 to 55%, from 39 to 55%, and from 5 to 15%. The share of 2-nuclear cells varied
      from 0 to 6%. The average square of tetraploid cells is more than that of diploid
      cells. In cells of a given size the protein content is higher in cells with
      higher ploidy, but the difference is not of 2-fold value. Larger 2c and 4c cells
      had more protein. In all the patients examined, along with myocytes with normal
      ultrastructure, some myocytes with different degree of organelle damage were
      observed, whose share varied in different patients. Myocytes with moderately to
      heavily damaged organelles are of more frequent occurrence in patients who
      displayed as well the highest myocyte hypertrophy and the largest share of
      polyploid cells.

PMID- 8525546
TI  - [The isolation and characteristics of a protein from human and bovine kidneys
      close in molecular and biochemical properties to non-histone chromosomal antigen
      PP23].
AB  - By ion-exchange gradient chromatography, autophosphorylated protein fractions
      were separated from nonhistone chromosomal protein (NHCP) samples isolated from
      bovine and human kidney and liver. Fractions, eluted from the phosphocellulose
      column with 0.4-0.5 M NaCl, could occur only in the case of kidney rather than
      liver NHCP-fractionation. The molecular weight of the major phosphorylated
      protein component, eluted in this zone, is about 20-26 kDa, which is close to the
      molecular weight of protein pp23, previously observed during similar
      fractionation of NHCP from rat kidney rather than from liver.

PMID- 8525547
TI  - [The effect of millimeter-range electromagnetic and of ionizing radiation on the
      body and thymocytes of mice and rats].
AB  - Radiomodifying effects of ultra-high frequency electromagnetic radiation (UHFER)
      were studied using laboratory mice and rats, as well as irradiated rat thymocytes
      in vitro. The resistance of mice to lethal effects of X irradiation was increased
      by preceding UHF treatment at 7.1 mm wavelength. By means of electron
      paramagnetic spin resonance, it was revealed that UHFER induced a sufficient
      decrease in free radicals and iron-binding proteins in rat thymus following UHF
      irradiation in vivo. The UHFER of rat thymocytes caused similar changes in
      Acridine orange binding to cellular DNA, light scatter parameters of thymocytes,
      their own UV fluorescence and partition in two phase systems as X irradiation.
      Possible mechanisms of these effects are discussed.

PMID- 8525548
TI  - [Membrane transport and functions of cell. Meeting abstracts].

PMID- 8525549
TI  - The relevance of dose-fractionation in tomography of radiation-sensitive
      specimens.
AB  - It is commonly assumed that the number of projections required for single-axis
      tomography precludes its application to most beam-labile specimens. However,
      Hegerl and Hoppe have pointed out that the total dose required to achieve
      statistical significance for each voxel of a computed 3D reconstruction is the
      same as that required to obtain a single 2D image of that isolated voxel, at the
      same level of statistical significance. Thus a statistically significant 3D image
      can be computed from statistically insignificant projections, as long as the
      total dose that is distributed among these projections is high enough that it
      would have resulted in a statistically significant projection, if applied to only
      one image. We have tested this critical theorem by simulating the tomographic
      reconstruction of a realistic 3D model created from an electron micrograph. The
      simulations verify the basic conclusions of the theorem and extend its validity
      to the experimentally more realistic conditions of high absorption, signal
      dependent noise, varying specimen contrast and missing angular range. Individual
      projections in the series of fractionated-dose images could be aligned by cross
      correlation because they contained significant information derived from the
      summation of features from different depths in the structure. This latter
      information is generally not useful for structural interpretation prior to 3D
      reconstruction, owing to the complexity of most specimens investigated by single
      axis tomography. These results demonstrate that it is feasible to use single-axis
      tomography with soft X-ray and electron microscopy of frozen-hydrated specimens.

PMID- 8525550
TI  - Double-tilt electron tomography.
AB  - Fidelity of tomographic reconstructions is improved and reconstruction artifacts
      are reduced, without increasing the number of projections, by combining tilt
      series taken around two orthogonal axes. Test reconstructions were made from high
      voltage EM of rat liver mitochondria in a 0.6 micron thick plastic section. A
      number of schemes for selecting tilt angles for the projections are compared. A
      new method for aligning fiducial markers is described. It uses an iterative
      algorithm to determine the shift, scale, in-plane rotation and tilt angle for
      each tilt image, enforcing agreement of the expected locations of the fiducial
      markers in 3D space. These 3D locations are used to find the orientation between
      two tilt series and to merge both sets of projections.

PMID- 8525551
TI  - Computerised transient hyperaemic response test--a method for the assessment of
      cerebral autoregulation.
AB  - A simple bedside test has been developed to assess the state of autoregulation in
      subarachnoid haemorrhage patients. Transcranial Doppler was used to measure blood
      flow velocity in the middle cerebral artery after a brief common carotid
      compression. Acceleration of blood flow postcompression was interpreted as
      evidence of intact cerebral autoregulation. A program using the Windows
      environment was designed for signal analysis of the transient hyperaemic response
      test (THRT). The flow velocity signal from the TCD was recorded, carotid
      compression and release automatically detected and the test results immediately
      displayed and stored in a database. The program was verified in 614 tests; 552 of
      them were analysed off-line using previously recorded data and 62 on-line during
      the examination. A significant correlation was found between the results of
      computerised testing and the patient's neurological state.

PMID- 8525552
TI  - Monitoring intracranial dynamics by transcranial Doppler--a new Doppler index:
      trans systolic time.
AB  - Since the introduction of transcranial Doppler sonography (TCD) several
      investigators have described the relationship between raised intracranial
      pressure (ICP) and Doppler waveform. This waveform has been expressed by several
      indices, such as the pulsatility index (PI) and the resistance index (RI). These
      indices are used to demonstrate the presence of raised ICP. In childhood
      hydrocephalus this information can be used to indicate the need for shunt
      implantation. However, PI and RI do prove to have certain disadvantages as both
      are strongly influenced by the heart rate. Moreover, both indices have a broad
      range of reference values, especially in children. Therefore, they are not very
      reliable for detecting insidious changes in the ICP. These drawbacks are due to
      the fact that these indices are composed of blood flow velocity measurements and
      do not embody the slope of the TCD waveform itself. An ideal TCD waveform
      analysis should be performed concerning the time-related changes of the
      velocities. We present a hydrodynamic model, with its electrical analogue, which
      shows the effects of raised ICP on the intracranial hemodynamic system. Based on
      these physical findings we define a new Doppler index, the Trans Systolic Time,
      reflecting specific changes in the TCD waveform induced by changes in the mean
      ICP. The applicability of this index, compared with PI and RI, is illustrated by
      consecutive simultaneous TCD and AFP measurements in three children with
      hydrocephalus.

PMID- 8525553
TI  - Effects of stenosis on transit-time ultrasound measurements of blood flow.
AB  - Measurement of blood flow with transit-time ultrasound near atherosclerotic
      stenosis sometimes yields anomalous results. The flow-versus-time waveform
      develops a chaotic pattern obscuring its pulsatile character, and the measured
      average flow may be less than the real flow thought present. Believing that
      disturbed flow secondary to atherosclerotic stenosis interferes with transit-time
      measurements, we investigated the effects of stenosis in a bench model of
      arterial flow. The average flow measurements and flow-versus-time waveforms
      produced by the transit-time flowmeter were studied in relation to: (1) the
      position of the transit-time probe proximal or distal to a stenosis; (2) the
      choice of filters employed to process the analog output from the flowmeter; and
      (3) the severity of the stenosis. The results confirm that high grade (> 50%)
      stenosis creates a characteristic chaotic artifact in the transit-time waveform
      and, when severe, causes an underestimation of flow.

PMID- 8525554
TI  - Segmentation and analysis of colour Doppler images of tumour vasculature.
AB  - A technique has been developed to segment (separate), from a digitized colour
      Doppler video image, the colour and greyscale information and then to estimate
      from the colour information the original mean Doppler frequency shift data from
      which the image was created. The remapped velocity image is then analysed to
      extract numerical features of the tumour vasculature. The present version of the
      software is set-up to work for an Acuson 128 colour Doppler system using the V4
      colour scale, although it should work well with any system which modulates only
      two colours for each flow direction and displays a colour calibration scale at
      the side of the image. Accuracy of classification of greyscale, colour and flow
      direction was estimated as being in the region of 95% for typical breast tumour
      images. The degree of agreement between the remapped colour velocity values and
      those stated by the scanner at the same image locations was evaluated in terms of
      the linearity of the relationship (> 99%), precision (better than +/- 5%) and
      accuracy (better than 7.6%). We investigated the value, for diagnosis and
      assessment of response of, a variety of characteristics of the displayed
      vascularity. At present, the software calculates the following vascular image
      features within any region of interest defined by the operator: mean displayed
      velocity, maximum displayed velocity, standard deviation of displayed velocity,
      total area occupied by colour signal, percentage area occupied by colour signal,
      area integral of displayed velocity and the total displayed velocity per unit
      area.

PMID- 8525555
TI  - Ultrasound-guided microwave thermotherapy on a VX-2 carcinoma implanted in rabbit
      kidney.
AB  - A temperature greater than 60 degrees C was maintained for 60 s within a 5-mm
      radius of a microwave electrode implanted in a rabbit kidney using 2450 MHz at
      100 W for 30 s. Histological examination revealed complete coagulation necrosis
      in that area. VX-2 cells were inoculated into the kidneys of 10 rabbits. One week
      later, five rabbits received ultrasound-guided microwave thermotherapy, and the
      remaining five rabbits received no treatment. All rabbits with microwave
      thermotherapy had a complete response to treatment while all rabbits without
      therapy died of cancer within 6 weeks of the VX-2 implantation. These results
      indicate that ultrasound-guided microwave thermotherapy has the potential of
      being a nephron-salvaging treatment for small renal tumors.

PMID- 8525556
TI  - The butterfly search technique for estimation of blood velocity.
AB  - We present a novel, robust and accurate blood velocity estimation technique that
      is implementable by elementary digital signal processing. In this technique,
      echoes from repeated firings of a transducer are resampled along a set of
      predetermined trajectories of constant velocities, called "butterfly lines"
      because of their intersection at a reference range. The slope of the trajectory
      on which the sampled signals satisfy a predetermined criterion appropriate for
      the type of signal in question, provides an estimate of the velocity of the
      target. The search for this trajectory is called "butterfly search," which can be
      carried out efficiently in a parallel processing scheme. The estimator can be
      based on the RF echo, its envelope, or its quadrature components. We present the
      theory of the butterfly search and some preliminary results. The butterfly search
      on quadrature components has shown superior noise immunity, with relatively few
      successive scan lines, and was found to outperform all the common time domain and
      Doppler techniques in simulations and phantom experiments with strong noise. The
      butterfly search can overcome many disadvantages faced by the present day
      techniques, such as the stringent tradeoff criterion between imaging resolution
      and velocity resolution implicit in Doppler techniques, and the need for
      computation-intensive operations.

PMID- 8525557
TI  - Bias in mean frequency estimation of Doppler signals due to wall clutter filters.
AB  - Wall clutter filters used in Doppler ultrasound systems give rise to a bias in
      the mean frequency estimation. This effect has been explored for two second order
      filters: the initialised infinite impulse response (IIR)-type filter, and the
      finite impulse response (FIR) echo-canceller filter. These are used in
      conjunction with two mean frequency estimation algorithms: the FFT-based
      intensity-weighted-mean algorithm, and the autocorrelation algorithm. The bias is
      shown to be caused by the finite settling times of the filters. The IIR filter,
      although having a much better frequency response than the FIR filter, has a
      greater bias associated with it. A compromise between bias and frequency response
      is suggested and a simple method of bias correction is described.

PMID- 8525558
TI  - Demonstration of three-dimensional vector flow estimation using bandwidth and two
      transducers on a flow phantom.
AB  - A method of performing three-dimensional (3-D) velocity vector estimation with
      two transducers is demonstrated on a flow phantom using the Doppler spectra's
      mean frequencies and bandwidths. The results are compared with 3-D vector
      estimates computed from Doppler mean frequencies obtained with a five-transducer
      system. It is shown that the two-transducer vector Doppler system which uses
      bandwidth can improve on the accuracy of a three-transducer vector Doppler system
      which relies only on Doppler mean frequencies.

PMID- 8525559
TI  - Cardiac ultrasound phantom using a porcine heart model.
AB  - A beating cardiac phantom has been developed using an excised porcine heart for
      use as a training tool in echocardiography. The heart is fixed with a formalin
      based preservation method, housed in an optically transparent Lexan chamber, and
      undergoes hydraulic pumping to circulate a blood-mimicking fluid. The cardiac
      phantom has been used for a period of four months to produce images of excellent
      quality with ventricular wall motion typical of human subjects.

PMID- 8525560
TI  - A survey of the acoustic outputs of diagnostic ultrasound equipment in current
      clinical use.
AB  - Surveys published up to 1991 have highlighted a steady increase in the acoustic
      outputs from diagnostic ultrasound equipment. Since 1991 we have made
      measurements of the maximum peak negative pressure (p-) and spatial peak temporal
      average intensity (ISPTA) produced by 223 probes from 82 scanning systems in
      current clinical use in the Northern Region in the UK. Measurements have also
      been made of the maximum total acoustic power generated by 45 probes from 17
      scanners. The results from these measurements are presented in this article and
      compared to the results of a similar survey of equipment from both the Northern
      and Wessex Regions in the UK and published in 1991. The comparison shows that
      measured ISPTA values have increased approximately sixfold in B mode and
      approximately threefold in colour Doppler mode. Also, measured total acoustic
      power values have doubled in pulsed Doppler mode. The present survey also draws
      attention to some particularly high ISPTA values obtained from a number of probes
      and scanning systems. This survey has shown that measurements of acoustic outputs
      from diagnostic ultrasound scanners in current clinical use are substantially
      higher than reported in earlier surveys and, for certain scanners, the acoustic
      outputs from scanned beam modes of operation can reach levels hitherto only found
      in pulsed Doppler mode.

PMID- 8525561
TI  - Acoustic energy determines haemoglobin release from erythrocytes by
      extracorporeal shock waves in vitro.
AB  - Haemoglobin release from erythrocytes by extracorporeal shock waves from an
      electrohydraulic lithotripter was quantified and correlated with the acoustic
      energy administered to the cell container. Cells were exposed in 2-, 5.9-, and
      10.5-mL vials to 100 shock waves delivered at a low, medium and high lithotripter
      output setting, both with and without covering of the central ellipsoidal axis by
      a metal cage. Using the identical set-up, previous experiments had shown that the
      fragmentation efficiency was linearly correlated with the delivered acoustic
      energy. As a result, shock waves generated from 0.83 microgram mJ-1 (in 2-mL
      vials) to 1.53 micrograms mJ-1 (in 10.5-mL vials) haemoglobin. At all vial types,
      the amount of haemoglobin correlated linearly with the delivered acoustic energy
      (r = 0.96 in 2-mL, r = 0.97 in 5.9-mL and r = 0.98 in 10.5-mL vials). It was
      independent of the presence of the cage.

PMID- 8525562
TI  - Effects of ultrasound on agglutination and aggregation of human erythrocytes in
      vitro.
AB  - A new experimental approach has shown that human erythrocytes of different blood
      groups were induced to form more agglutinates at a sound pressure of 70-240 kPa
      in vitro than the control erythrocytes. Similar effects were observed for alcian
      blue and dextran stimulated aggregation and for spontaneous aggregation. The
      increase of agglutination or aggregation was reversible. Heating and acoustic
      cavitation were shown not to be responsible for this effect. Bulk fluid movement
      produced by ultrasound irradiation appeared to cause the described phenomenon.
      Possible underlying mechanisms connecting the acoustic streaming and
      agglutination or aggregation behaviour of the cells are proposed.

PMID- 8525563
TI  - A schlieren study of the interaction between a lithotripter shock wave and a
      simulated kidney stone.
AB  - The interaction between a lithotripter shock wave and a simulated kidney stone
      has been imaged using laser illuminated schlieren photography. The images clearly
      show the incident, transmitted and reflected components of the shock wave and the
      associated cavitation.

PMID- 8525564
TI  - An estimation method for blood flow velocity profiles in vessels.

PMID- 8525565
TI  - Grooming.
AB  - Although cats are low-maintenance pets, routine grooming provides medical
      benefits and enhances the interaction between pet owner and cat. The methods of
      restraint, necessary equipment, clipping and bathing procedures, and special
      situations are discussed.

PMID- 8525566
TI  - Diagnostic procedures in feline dermatology.
AB  - No substitute exists for diligence and meticulous care in the performance of
      these diagnostic procedures. The test results are only as good as the technique
      used to collect the data.

PMID- 8525567
TI  - The cat, the flea, and pesticides.
AB  - Recent advances in our knowledge of cat flea biology and the discovery of new
      nontoxic control methods have greatly simplified and improved flea control.
      Instead of relying on adulticides for the bulk of flea control, the veterinarian
      now focuses on the immature stages, particularly the larvae and the eggs. By
      doing this, environmentally "friendly" flea control methods are employed that are
      much safer for the veterinarian, the pet owner, and the cat.

PMID- 8525568
TI  - Exudative, crusting, and scaling dermatoses.
AB  - This article discusses the differential diagnoses for the dermatologic diseases
      of the cat that present with the primary owner complaint of scaling, crusting,
      and exudation. Clinical signs, diagnostic tests, and therapies are included for
      each disease.

PMID- 8525569
TI  - Selected feline eosinophilic skin diseases.
AB  - Eosinophilic plaque and mosquito-bite dermatitis are recognized hypersensitivity
      reactions. The pathogenesis of eosinophilic granuloma and indolent ulcer are not
      as clearly understood. Each of these syndromes is distinctive from a clinical and
      histopathologic view point. Accurate diagnosis depends on history, physical
      findings, and histopathologic evaluation. Understanding of feline dermatology
      will be furthered by including these syndromes in a broader grouping that
      encompasses all the feline eosinophilic dermatoses.

PMID- 8525570
TI  - Focal and generalized alopecia.
AB  - Focal or generalized alopecia is defined as hair loss affecting the ventral,
      lateral, perineal, and dorsal aspects of the trunk of the cat, usually in a
      symmetric pattern. This may be attributable to failure of hair coat production,
      excess loss of hair due to self trauma, or excess shedding of whole hairs. Self
      trauma is the most common cause of hair loss and is associated particularly with
      flea allergy dermatitis. Other causes of hair loss are reviewed.

PMID- 8525571
TI  - Erosive and ulcerative skin disease.
AB  - Many causes exist for ulcerative disease of the skin and mucous membranes of
      cats. History, physical examination, cytology, skin biopsy, a hemogram, serum
      biochemical evaluation, and FeLV and feline immunodeficiency virus testing are a
      standard diagnostic protocol for such cases. Therapy is dependent on the
      underlying cause. Symptomatic therapy consisting of cleansing soaks
      (chlorhexidine) and systemic antibiotics (trimethoprim-sulfadiazine or
      amoxicillin-clavulanic acid) may be helpful to control secondary bacterial
      infections. If ulceration is widespread, serum leakage may result in a decreased
      total protein and more systemic signs. When oral ulcers are present, food and
      water consumption may be affected. Enteral nutrition may be helpful to sustain
      the cat during the diagnostic workup or until results of treatment are evident.

PMID- 8525572
TI  - Nodules and draining tracts.
AB  - Many potential causes exist of nodules and draining tracts in cats. Treatment
      should not be undertaken until a definitive diagnosis is made. This may involve
      biopsies for histopathologic evaluation, sample collection and submittal for
      culture and sensitivity, cytologic evaluation of impression smears or needle
      aspirates, and serologic testing.

PMID- 8525573
TI  - Feline dermatophytosis. Recent advances and recommendations for therapy.
AB  - Feline dermatophytosis is one of the most common skin diseases of cats. In the
      past, much of the information available on this subject stemmed from clinical
      observations. This article summarizes current research findings on the
      epidemiology, immunology, pathogenesis, and treatment of feline dermatophytosis.
      As a result of these studies, the authors propose new recommendations for
      treatment.

PMID- 8525574
TI  - Facial, pedal, and other regional dermatoses.
AB  - This article discusses disorders of the head and face, including feline acne,
      solar dermatoses, pruritus of the head and neck, and nodular or ulcerative
      dermatoses of the head. Disorders of the pinna, otitis externa, and nasal
      diseases are highlighted. In addition, a discussion of pododermatitis and
      diseases of the claws and ungual fold is presented. Miscellaneous regional
      dermatoses include midline ulcerative dermatitis, stud tail, and vaccine-induced
      lesions.

PMID- 8525575
TI  - Systemic diseases with cutaneous manifestations.
AB  - The purpose of this article is to briefly discuss the following cutaneous
      manifestations of selected systemic diseases: poxvirus; feline leukemia virus
      (FeLV); feline immunodeficiency virus (FIV); herpesvirus; calcivirus;
      pseudorabies; plague; tularemia; toxoplasmosis; leishmania; hypothyroidism;
      hyperthyroidism; hyperadrenocorticism; diabetes mellitus; acromegaly; thallium
      poisoning; pancreatic disease; hypereosinophilic syndrome; mucopolysaccharidosis;
      and pansteatitis. Recognition of these cutaneous signs may help alert the
      clinician to the possibility of an internal disorder so that the appropriate
      diagnostic tests can be considered.

PMID- 8525576
TI  - Feline cutaneous and subcutaneous neoplasms.
AB  - This article contains practical information about the more common feline skin
      tumors and an update on recent treatments. The tumor type, gross appearance,
      clinical behavior, prognosis, and treatment are provided.

PMID- 8525577
TI  - Therapy for feline dermatoses.
AB  - This article compiles information on various therapies used in feline
      dermatology. Information on the following therapeutic agents and devices is
      discussed: antibiotics, antifungals, antileprosy drugs, antiparasiticides,
      antivirals, antihistamines, behavior modification drugs, fatty acids,
      progestogens, steroids, immunomodulating drugs,
      chemotherapeutic/immunosuppressive agents, retinoids, mechanical devices,
      hyposensitization, immunotherapy, food elimination trials, hypoallergenic diets,
      and miscellaneous topical agents such as polyhydroxydine solution, tar, and
      benzocaine-containing creams.

PMID- 8525578
TI  - NFU sets out its position on farm animal welfare.

PMID- 8525579
TI  - Effects of the sucking louse (Linognathus vituli) on the grooming behaviour of
      housed calves.
AB  - The behaviour of cattle with and without louse infestation was studied for eight
      weeks. Thirty-two crossbred calves were housed in groups of four at 20 weeks old.
      Sixteen of the calves were artificially infested with the long-nosed cattle louse
      Linognathus vituli and 16 were left uninfested as controls. In infested animals
      the number of lice on the shoulders averaged 2.3 per 10 cm length of parted hair.
      The recorded frequency of irritation, manifested by rubbing and self-licking, was
      significantly greater in the louse-infested calves than in the uninfested
      controls. The infested calves spent 28 s/h rubbing and 95 s/h self-licking,
      compared with 8 s and 62 s/h spent by the uninfested controls. The infested
      calves also spent more than twice as long scratching as the controls. There were
      no significant effects of the infestation on social grooming.

PMID- 8525580
TI  - The prevalence of abnormal behaviours in dressage, eventing and endurance horses
      in relation to stabling.
AB  - The behaviour of horses competing in different disciplines was studied and the
      relationship between the time they spent out of the stable and the prevalence of
      abnormal behaviour was examined. The owners of dressage, eventing and endurance
      horses were sent a questionnaire and a total of 1101 responses were received,
      giving data on 1750 horses. The behaviours studied were wood-chewing, weaving,
      crib-biting/wind-sucking and box-walking. The reported percentage prevalences of
      abnormal behaviour for the dressage, eventing and endurance horses were 32.5,
      30.8 and 19.5, respectively. The relationship between the time spent in the
      stable and the prevalence of abnormal behaviour was examined by chi 2 tests which
      showed that there were significant linear trends for the eventing group (P <
      0.001) and the dressage group (P < 0.05). It is concluded that the time a horse
      spends out of the stable is related to the discipline for which it is being
      trained and in dressage and eventing horses the time spent in a stable is
      correlated with an increased risk of abnormal behaviour.

PMID- 8525581
TI  - Responses of calves to injections of ACTH and their relationship with growth
      rate.
AB  - A study was made of the effects of exogenous adrenocorticotropin (ACTH) on the
      levels of blood components in 109 dairy replacement calves and the statistical
      correlations between these effects and the growth rates of the calves from birth
      to six months. Blood samples were taken from a jugular vein before ACTH was
      injected and then at two, four, six and eight hours afterwards, and analysed for
      plasma cortisol concentration, total white cell counts, packed cell volume,
      haemoglobin, plasma glucose, sodium, potassium, magnesium and inorganic
      phosphorus, erythrocyte sodium, potassium and magnesium, serum ionised calcium
      and total protein and total plasma calcium concentration. The injection of 1.1 +/
      0.02 iu/kg of ACTH intramuscularly resulted in a peak plasma cortisol
      concentration after two hours which had not returned to normal after eight hours.
      It also resulted in leucocytosis, lymphopenia, neutrophilia, eosinopenia and
      hypophosphataemia; the mean changes were repeatable (P < 0.05) in 49 of the
      calves tested two months later. The weight gains to six months of age could be
      predicted from the degree of the changes in several blood constituents.
      Significant partial regression coefficients were found for the change in glucose
      concentration (0 to four hours), absolute neutrophil count (0 to two hours),
      absolute lymphocyte count (0 to four hours) and loge absolute eosinophil count (0
      to two hours). The multiple regression sum of squares was highly significant (P <
      0.0001), and the multiple coefficient of determination was 0.305. It was
      concluded that the changes in these blood components after an injection of ACTH
      might be used to predict the weight gains of dairy replacement calves.

PMID- 8525582
TI  - Bipartite distal sesamoid bones in a Holstein-Friesian calf.
AB  - Bipartite distal sesamoid bones were observed in the medial digits of both
      forelimbs of a six-month-old Holstein-Friesian calf. This paper describes the
      clinical and radiological (including computed tomographic) findings, and the
      therapy and follow-up of the case.

PMID- 8525583
TI  - Multiple resistance to ivermectin and oxfendazole in Cooperia species of cattle
      in New Zealand.

PMID- 8525584
TI  - Efficacy of pyrantel embonate and praziquantel against the equine tapeworm
      Anoplocephaloides mamillana.

PMID- 8525585
TI  - First report of canine ehrlichiosis in Costa Rica.

PMID- 8525586
TI  - Evaluation of a homoeopathic treatment for subclinical mastitis.

PMID- 8525587
TI  - Apparent resistance of P ovis to flumethrin.

PMID- 8525588
TI  - Socialising puppies.

PMID- 8525589
TI  - Prescription of veterinary drugs in fish farming.

PMID- 8525590
TI  - 'Stupid calves'.

PMID- 8525591
TI  - Docking and other practices.

PMID- 8525592
TI  - Neospora encephalomyelitis in a calf.

PMID- 8525593
TI  - Residues of clenbuterol in cattle receiving therapeutic doses: implications for
      differentiating between legal and illegal use.
AB  - Clenbuterol (CBL) can be used legally in the treatment of respiratory diseases
      and illegally as a growth promoter in animals. Liver and eye have previously been
      shown to be effective matrices for the detection of residual concentrations of
      the drug. The pharmacokinetics of CBL in therapeutically treated cattle were
      investigated. During treatment, many body fluids and tissues contained residues
      of the drug. After a 14 day withdrawal only eyes (mean 27.1 micrograms/kg), and
      to a much lesser extent lung and kidney (mean 0.3 micrograms/kg), contained
      detectable residues. By day 28 of withdrawal only residues in eyes were present
      (mean, 6 micrograms/kg). These persisted to the end of the trial (42 days
      withdrawal). It is concluded that it is not possible to differentiate between the
      legal and illegal use of CBL solely on drug residue analysis. Other information
      must be made available to regulatory bodies to enforce control programmes.

PMID- 8525594
TI  - Bilateral lameness in horses--a kinematic study.
AB  - The kinematic pattern of mild bilateral lameness was studied by inducing a
      supporting limb lameness in both fore-limbs of 11 sound Dutch Warmblood horses.
      The kinematics of the horses were recorded while they trotted (3.5 m/s) on a
      treadmill. The locomotion analysis system CODA-3 was used to determine the
      temporal stride patterns, limb movements as well as head and trunk movement
      patterns. The transient lameness model, by which pressure-induced pain is evoked
      on the hoof sole, was used. Differences between left and right limbs as well as
      between the sound and the lame condition were tested using a paired t-test.
      Stride and stance duration did not change significantly (p < 0.05) during
      bilateral lameness compared to the pattern of sound horses. Diagonal advanced
      placement changed to an earlier placement of both forelimbs. Fetlock
      hyperextension decreased also in both forelimbs, while the pro- and retraction,
      hoof impact angle, maximal hoof height, and all hind limb variables remained
      unchanged. Vertical head and trunk movements tended to decrease, but these
      changes were not significant. It was concluded that fetlock hyperextension and
      diagonal advanced placement indicate locomotor disturbances, but that mild
      bilateral lameness may be difficult to distinguish from individual patterns in
      single assessments because of the lack of locomotor asymmetries. Evaluation of
      these variables at regular intervals may allow an early detection of bilateral
      lameness, which then could be confirmed by diagnostic local anaesthesia.

PMID- 8525595
TI  - A survey of the relationship between bile staining and oesophagogastric lesions
      in slaughter pigs.
AB  - In 280 slaughter pigs, the oesophageal region of the stomach was examined to test
      the hypothesis that there is a (causal) relationship between the intensity of
      bile staining of oesophagogastric tissue due to bile regurgitation and the
      severity of oesophagogastric lesions. When the stomachs were opened, almost all
      stomachs contained bile and 99.6% of stomachs showed bile staining of the pars
      oesophagea. A total of 14.3% of the stomachs showed distinct erosions and/or
      ulceration. A considerable proportion of the stomachs (58.5%) had hyperkeratosis
      as the only lesion. Only two animals showed a completely intact epithelium. There
      was no evidence for an increased proportion of oesophagogastric lesions with an
      increased intensity of bile staining. No dark yellow to green staining was
      observed; a just detectable to an obvious yellow was seen. This is an indication
      for bile regurgitation of recent origin. Therefore, there is no evidence for the
      hypothesis that the regurgitation of bile into the stomach is positively linked
      to the occurrence of oesophagogastric lesions in fattening pigs. It is suggested
      that various factors associated with slaughter, such as fasting and slaughter
      procedure, are primarily responsible for the presence of bile and the staining of
      the pars oesophagea in the stomachs.

PMID- 8525596
TI  - Progressive ataxia in a rottweiler dog.

PMID- 8525597
TI  - An observational study into herd-level risk indicators of return to oestrus more
      than five days after insemination in sow herds.
AB  - In a study population of 90 sow herds in the southern Netherlands, the occurrence
      of sows returning to oestrus more than five days after insemination (SRO) was
      investigated. In these herds information with regard to the herd system, herd
      size, and breeding management was recorded. The occurrence of SRO was recorded
      with the on-farm computer management system CBK-plus. The incidence of SRO was
      defined as the average number of gilts or sows returning to oestrus more than
      five days after insemination per 100 first inseminations. The average incidence
      of SRO in the study population was 18.3 per 100 first inseminations. Multivariate
      analysis resulted in a model with a significant effect of herd operation (herds
      with only sows had a lower incidence of SRO than herds with sows and finishing
      pigs), breeding strategy (herds with two or more inseminations per oestrus in a
      sow had a lower incidence of SRO than herds with one insemination per oestrus)
      and percentage of sows artificially inseminated (a higher percentage of
      artificial insemination was associated with a higher incidence of SRO).

PMID- 8525598
TI  - Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adreno
      cortical tumour.
AB  - A total of 38 adrenocortical tumours were removed from 36 dogs with
      hyperadrenocorticism. The surgical approach was by way of a unilateral flank
      laparotomy (32 dogs; 14 left and 18 right), a bilateral flank laparotomy (3 dogs)
      or a midline celiotomy (1 dog). Two dogs were euthanized during surgery because
      their tumours could not be resected. Eight dogs died from post-operative
      complications. Pancreatic necrosis with peritonitis was the most common cause of
      death. Eight of the 26 dogs that survived had signs of recurrence of
      hyperadrenocorticism. Unsuppressible hyperadrenocorticism was found in four dogs;
      one dog had probably pre-existent pituitary-dependent hyperadrenocorticism, and
      adrenocortical function could not be re-examined in the remaining three dogs.
      Among the 37 tumours examined microscopically expansion of neoplastic tissue into
      blood vessels was found in 22 of them. Four adrenal glands with adrenocortical
      tumours also contained phaeochromocytomas. Necropsy was performed in eight dogs.
      Metastases were found in the lungs of two dogs and in the lungs and liver in one
      dog. In combination with the data of previous reports, it is suggested that
      histological findings in surgery specimens are not good predictors for the
      clinical outcome.

PMID- 8525599
TI  - Bovine respiratory syncytial virus reinfections and decreased milk yield in dairy
      cattle.
AB  - The influence of Bovine Respiratory Syncytial Virus (BRSV) reinfections on the
      daily milk yield was studied by evaluating the milk production of 32 BRSV
      reinfected cows. For the estimation of milk production losses, four lactation
      curve models were used, including a gamma function, a second degree polynomial,
      and both of these models with a lag variable. Bovine respiratory syncytial virus
      reinfections seemed to have only a small effect on the daily milk production.
      Comparison of the true production with an estimated production according to the
      gamma function showed that the production for first lactation cows dropped 0.14
      kg on average and for cows in their second or later lactation 0.56 kg on average,
      during 5 consecutive days in the infection period. For the second-degree
      polynomial model these values were respectively 0.42 kg and 0.80 kg. All
      calculated average production losses were relatively small and not significant (P
      > 0.15). The models without lag variable were more suitable than the models with
      the lag variable to estimate small production losses caused by BRSV reinfections.
      The power of this study was sufficient to detect a decrease in production of
      approximately 1-1.5 kg milk per cow per day. It was therefore concluded that BRSV
      reinfections were not associated with an important loss of milk production.

PMID- 8525600
TI  - Oral bioavailability of sulphonamides in ruminants: a comparison between
      sulphamethoxazole, sulphatroxazole, and sulphamerazine, using the dwarf goat as
      animal model.
AB  - The various sulphonamides show marked differences in disposition characteristics
      after administration to ruminants. For use in combination with a
      diaminopyrimidine derivative such as trimethoprim or baquiloprim, it is essential
      that a sulphonamide has similar pharmacokinetic properties in order to obtain
      optimal synergy. In the present study the pharmacokinetics of sulphamethoxazole,
      sulphatroxazole, and sulphamerazine were investigated in dwarf goats (n = 6)
      after IV and intraruminal administration at a dose of 30 mg/kg bodyweight. In
      addition, the in vitro binding of sulphamerazine to ruminal contents was studied
      as a possible explanation for a reduced absorption rate. Sulphamethoxazole showed
      the most rapid absorption after intraruminal administration (mean tmax +/- SD :
      0.8 +/- 0.2h). However, the drug was rapidly eliminated from the plasma (t1/2
      beta : 2.4 +/- 1.5 h) and the bioavailability was only 12.4 +/- 4.7%, most likely
      due to an extensive 'first-pass' effect. The bioavailability of orally
      administered sulphamerazine and sulphatroxazole was much higher (67.6 +/- 13.5%
      and 70.2 +/- 32.3%, respectively). After intraruminal administration,
      sulphatroxazole showed the highest plasma peak concentration (26.1 +/- 6.3 mg/l)
      and the longest plasma half-life (4.7 +/- 1.8h) and mean residence time (13.9 +/-
      4.5 h). Sulphamerazine showed considerable binding to rumen contents in vitro.
      Based on its pharmacokinetic properties sulphatroxazole appears to be a suitable
      candidate to be used in combination with the more recently developed
      diaminopyrimidines such as baquiloprim.

PMID- 8525601
TI  - Prevalence of antibodies to Toxoplasma gondii in cattle and swine in The
      Netherlands: towards an integrated control of livestock production.
AB  - Serological surveys of the prevalence of antibodies against Toxoplasma gondii
      were carried out amongst swine and cattle in the Netherlands. Data were analysed
      according to the different categories of animals. The results show very low
      seroprevalences of Toxoplasma gondii in finishing pigs (1.8%) and in fattening
      calves (1.2%). In sows and dairy cattle, respectively, seroprevalences of 30.9%
      and 27.9% respectively, were found, demonstrating clearly the environmental
      infection pressure and illustrating the importance of housing and management in
      establishing low infection rates. Substantially different seroprevalences were
      found between dairy cattle sampled in the North and in the South of the
      Netherlands (13.1% and 42.6%, respectively). The infection rates in the samples
      from finishing pigs, fattening calves, and dairy cattle demonstrate that
      seroprevalences in individual farms or herds may differ considerably.
      Investigation of the factors involved can be useful in determining the causes of
      infection and for developing measures with regard to prevention. The very low
      seroprevalences in finishing pigs and fattening calves indicate, however, that
      the production of toxoplasma-free meat may be well within reach in modern
      husbandry. Since farm animals easily are infected, serological screening of
      individual farms or herds for the absence of T. gondii infection, as a part of
      the Integrated Quality Control programme, can be helpful in determining the
      quality of livestock production and in developing certain standards of hygiene
      for individual farms.

PMID- 8525602
TI  - Estimating sample sizes for a two-stage sampling survey of seroprevalence of
      pseudorabies virus (PRV)-infected swine at a regional level in The Netherlands.
AB  - In the European Union, vaccination campaigns against Pseudorabies virus (PRV) in
      swine have been started to eradicate PRV. Specific sampling designs are needed to
      monitor PRV seroprevalence at a regional level. This paper demonstrates how
      sampling theory can be applied to design a disease seroprevalence survey, using
      PRV as an example. In the spring of 1994, the four regions in the Netherlands
      covered by the regional Animal Health Services were monitored with respect to PRV
      seroprevalence. Per region, blood samples from approximately 1400 herds, with two
      animals per herd, were collected. The sampling design accounted for
      stratification by fattening pig and sow population within each region. The
      regional PRV seroprevalence of swine in the Southern region was the highest
      (24.9%), closely followed by the PRV seroprevalence of swine in the Eastern
      region (20.5%). These regions have the highest density of swine in the
      Netherlands. The PRV seroprevalence in the Western and Central region (11.7%) was
      about half of the seroprevalence in the Southern and Eastern regions; the lowest
      regional PRV seroprevalence was observed in the Northern region (3.5%). The
      Northern part also has the lowest pig density. The PRV seroprevalence was
      approximately two times higher in sows than in fattening pigs.

PMID- 8525603
TI  - Prevalence and development of antibodies neutralizing the haemolysin and
      cytotoxin of Actinobacillus pleuropneumoniae in three infected pig herds.
AB  - Sero-epidemiological studies were carried out in pigs aged 1 to 24 weeks in three
      herds in which Actinobacillus pleuropneumoniae was endemic. The sera were tested
      in the complement-fixation test and for their ability to neutralize the
      haemolytic and cytotoxic activities of the A. pleuropneumoniae serotypes isolated
      from the herds. Almost all (98%) sera from 1-week-old piglets neutralized the
      haemolytic and cytotoxic activities but only 21% fixed complement. At the end of
      the finishing period, most pigs (82%) had sera that neutralized haemolytic and
      cytotoxic activities and only 22% fixed complement. In longitudinal studies the
      neutralization titres decreased during the first 12-13 weeks of age. Thereafter,
      75% of the pigs had increased titres in the haemolysin- and cytotoxin
      neutralization tests and only 5% of the pigs had increased titres in the
      complement-fixation test. In none of these pigs were clinical signs of
      pleuropneumonia seen. Thus in these endemically infected herds the prevalence of
      complement-fixing antibodies was low, whereas the prevalence of neutralizing
      antibodies was high. The fact that serum-neutralizing titres are low in 12-week
      old pigs might be the reason that pigs of this age are the most vulnerable to the
      disease.

PMID- 8525604
TI  - Deletion analysis of the promoter for the cucumber necrosis virus 0.9-kb
      subgenomic RNA.
AB  - Sequences comprising the core promoter for the cucumber necrosis virus (CNV) 0.9
      kb subgenomic RNA have been determined using deletion analysis and site-directed
      mutagenesis. The deletion studies indicate that the promoter lies within a region
      located 20 nucleotides upstream and 6 nucleotides downstream and including the
      subgenomic start site. Sequences further upstream or downstream of the core
      promoter do not appear to strongly affect promoter activity or viral RNA
      accumulation. Results of site-directed mutagenesis studies indicate that
      nucleotides immediately surrounding the subgenomic start site regulate promoter
      activity. Comparison of sequences within the CNV promoter region with the
      corresponding region of other tombusviruses shows that the tombusvirus promoter
      shares a region of near complete identity in 14 of the 26 core promoter
      nucleotides. Little similarity exists between the CNV 0.9-kb subgenomic RNA
      promoter and the region surrounding the transcription initiation site for the CNV
      2.1-kb subgenomic RNA. Likewise, limited similarity occurs with the 5' region of
      CNV genomic RNA. Sequences similar to the ICR2-like motifs found in the promoters
      of several alphavirus-like (supergroup III) plant and animal viruses are not
      apparent. This study represents the first analysis of a subgenomic promoter from
      a member of supergroup II of positive-strand RNA viruses.

PMID- 8525605
TI  - Antigenic sites on the receptor-binding domain of human adenovirus type 2 fiber.
AB  - The trimeric fiber of adenovirus type 2 (Ad2) mediates the first stage of virus
      cell attachment, and the distal head region of the fiber has been implicated as
      the receptor-binding domain. To locate regions on the primary polypeptide
      sequence of the fiber which may be involved in virus-cell interaction, peptide
      based epitope mapping was performed using (1) polyclonal antibodies prepared
      against both native Ad2 fiber and Ad2 head protein expressed in Escherichia coli
      and (2) 18 monoclonal antibodies prepared against trimeric Ad2 head protein
      expressed in baculovirus. The approach using polyclonal antibodies revealed eight
      domains on the primary sequence of the head which contain one or more continuous
      epitopes. At least two of these regions were also recognized by monoclonal
      antibodies reacting against both monomeric and trimeric fiber head protein. The
      majority of monoclonal antibodies which did not recognize Ad2 head-specific
      peptides in ELISA were also nonreactive against the monomeric form of protein in
      Western blot, suggesting that their recognition of trimer is due to the existence
      of as yet undefined discontinuous epitopes or to alterations in monomer
      configuration. Our results correspond well with the recently published X-ray
      crystallographic model of Ad5 fiber head (D. Xia, L.J. Henry, R.D. Gerard, and J.
      Deisenhofer, Structure 2, 1259-1270, 1994), since most antigenic determinants
      containing linear epitopes mapped to the outer loops or uppermost beta-sheets in
      this structure. Four of five neutralizing monoclonal antibodies recognized trimer
      only and none recognized linear peptides. This might suggest that the trimeric
      form of fiber is necessary for making contact with the receptor(s) and that
      discontinuous epitopes on the head domain may be involved in fiber-cell
      interaction.

PMID- 8525606
TI  - Characterization of Mengo virus neutralization epitopes. II. Infection of mice
      with an attenuated virus.
AB  - A panel of five neutralizing monoclonal antibodies was generated from mice
      immunized with an attenuated strain of Mengo virus. Four of the antibodies were
      used to select mutants of Mengo virus which were able to escape neutralization by
      the selecting antibody, but it was not possible to select mutants which could
      escape neutralization by the fifth antibody. The capsid coding region of the RNA
      genome of each mutant was directly sequenced to identify the mutation(s)
      responsible for the neutralization escape phenotype. These results are compared
      to those of a previous study in which immunogenic determinants recognized by
      neutralizing antibodies generated against pentameric capsid subunits were located
      on the external surface of the Mengo virion. We have confirmed the existence of
      the previously identified immunogenic determinant in VP3 (site 2) as well as an
      immunodominant determinant in VP2 (site 1). Two previously uncharacterized
      determinants, located in surface loops of VP1 (sites 3 and 4A), were also
      identified. None of the mutations conferring the neutralization escape phenotype
      was found near the surface depressions on the virion which are believed to be the
      receptor binding sites.

PMID- 8525607
TI  - A feline herpesvirus-1 recombinant with a deletion in the genes for glycoproteins
      gI and gE is effective as a vaccine for feline rhinotracheitis.
AB  - Using a site-directed mutagenesis technique we constructed a new feline
      herpesvirus-1 recombinant strain containing a deletion in two genes encoding
      glycoproteins gI and gE. These proteins may have a role in virulence, the
      establishment of latency, and viral recurrence as shown in other herpesviruses of
      the varicella and simplex types. This recombinant was characterized and used to
      immunize juvenile cats against virulent virus challenge. Significant protection
      resulted from vaccination of cats by the subcutaneous route.

PMID- 8525608
TI  - A conserved motif at the 3' end of mouse hepatitis virus genomic RNA required for
      host protein binding and viral RNA replication.
AB  - A conserved 11-nucleotide sequence, UGAAUGAAGUU, at the 3' end of the genomic RNA
      of coronavirus mouse hepatitis virus was required for host protein binding and
      viral RNA synthesis. An RNA probe containing this 11-nucleotide sequence bound
      four cellular proteins with a highly labeled protein of 120 kDa and three minor
      species with sizes of 103, 81, and 55 kDa. Mutation of the 11-nucleotide motif
      abolished cellular protein binding. The RNA-protein complexes observed with
      cytoplasmic extracts from MHV-JHM-infected cells in both RNase protection/gel
      mobility shift and UV cross-linking assays were indistinguishable from those
      observed with extracts from uninfected cells. Both negative-strand synthesis and
      positive-strand replication of viral defective interfering RNAs in the presence
      of helper virus were affected by mutations that disrupt RNA-protein complex
      formation, even though the 11 mutated nucleotides were converted to the wild-type
      sequence, presumably by recombination with helper virus. Kinetic analysis
      indicated that recombination between DI RNA and helper virus occurred relatively
      early in the MHV replicative cycle at 5.5 to 7.5 hr postinfection, a time when
      viral RNA synthesis and replication of positive-strand DI RNA were at barely
      detectable levels. A DI RNA with a mutation upstream of the protein binding
      element replicated as efficiently as wild type without undergoing recombination.
      Thus, the 11-nucleotide conserved host protein binding motif appears to play an
      important role in viral RNA replication.

PMID- 8525609
TI  - Paramyxovirus phosphoproteins form homotrimers as determined by an epitope
      dilution assay, via predicted coiled coils.
AB  - When HA epitope-tagged and untagged Sendai virus (SeV) P proteins are coexpressed
      and the products reacted with anti-HA, the untagged P protein is also selected
      because this protein is found as an oligomer. The oligomer was determined to be a
      homotrimer by coselection studies in which increasing amounts of untagged versus
      tagged protein were coexpressed, and these findings were extended to mumps virus,
      a member of the rubulavirus genus. The region of the SeV protein responsible for
      the oligomerization was localized to residues 344-411. Computer analysis of the
      13 Paramyxovirus P proteins in the database revealed that all but one are
      predicted to form coiled coils in this region, the first of only two regions that
      can be aligned throughout the entire virus subfamily. The predicted coiled-coil
      region of the measles virus P protein, when grafted onto the C-terminus of the
      normally monomeric La protein, led to the efficient oligomerization of this
      reporter protein. The predicted coiled-coil region of these P proteins thus
      appears to be sufficient for oligomerization.

PMID- 8525610
TI  - Synthesis of a full-length infectious cDNA clone of cucurbit aphid-borne yellows
      virus and its use in gene exchange experiments with structural proteins from
      other luteoviruses.
AB  - A full-length cDNA of cucurbit aphid-borne yellows virus (CABYV) has been
      constructed and expressed either as an in vitro transcript, under control of a
      bacteriophage T7 RNA polymerase promoter, or in vivo, under control of the
      cauliflower mosaic virus 35S promoter in an agroinfection vector. The biological
      activity of the cloned cDNA was demonstrated by the ability of its in vitro
      transcript to replicate in protoplasts and of the agroinfection vector to infect
      agroinoculated plants. Virus in the agroinfected plants cold be transmitted by
      the aphid vectors Myzus persicae and Aphis gossypii. The specificity of
      luteovirus RNA packaging was investigated by replacing (1) the CABYV coat protein
      gene (and the overlapping ORF5) by the corresponding region of potato leafroll
      luteovirus or (2) the CABYV readthrough domain by the readthrough domain of beet
      western yellows luteovirus. The resulting chimeric transcripts replicated in
      protoplasts and produced virions.

PMID- 8525611
TI  - A potyvirus polymerase interacts with the viral coat protein and VPg in yeast
      cells.
AB  - The two-hybrid system was used to test for pairwise interactions between the
      tobacco vein mottling virus (TVMV)-encoded RNA-dependent RNA polymerase (or NIb
      protein) and two other TVMV-encoded proteins: the NIa protein, which consists of
      genome-linked protein (VPg) and proteinase domains, and the viral coat protein
      (CP). Using this approach, we find that the NIb protein interacts with both the
      NIa protein and the CP in yeast cells. Moreover, we find that a mutation in the
      conserved GDD domain of the NIb protein diminishes the NIb-CP interaction but not
      the NIb-NIa interaction. Likewise, mutations in the vicinity of the NIa protein
      to which the genomic RNA is covalently attached eliminate the NIb-NIa
      interaction. We conclude that the NIb protein interacts with the VPg domain of
      the NIa protein and that this interaction requires a functional RNA attachment
      site. This interaction may be important for the initiation of viral RNA synthesis
      in infected cells. We also conclude that the CP interacts with the NIb in a
      manner that is sensitive in changes in the highly conserved GDD motif. The role
      of this interaction in the functioning of the NIb protein or the CP is unclear,
      but may involve regulation of viral RNA synthesis in infected cells.

PMID- 8525612
TI  - Early phase in the infection of cultured cells with papillomavirus virions.
AB  - The fate of full bovine papillomavirus (BPV) virions and virus-like particles
      after binding to C127 or CV-1 cells was studied by electron microscopy and
      indirect immunofluorescence. After incubation at 4 degrees for 1 hr, BPV virions
      were found to be bound to the plasma membrane, and most viruses were absorbed by
      the cells after 30 min incubation at 37 degrees. Ninety minutes after the virions
      had been bound to the plasma membrane, the uptake of the virions was completed
      and most of the antigen was found to be localized in the nucleus. The viruses
      were transported in phagosomes and the uptake and transportation could be
      inhibited by cytochalasin B and taxol, suggesting the possible involvement of
      microfilaments and microtubules in the virus particle uptake and transportation.
      The capsid proteins could be detected for about 14 hr, until degradation and
      deposit of the viral antigen in the Golgi complexes. Although binding to the
      plasma membrane and uptake of virions into large cytoplasmic vesicles could be
      monitored by electron microscopy, no complete virions were observed in the
      nucleus of infected cells despite a very strong nuclear fluorescent staining for
      both L1 and L2 proteins. This may indicate that disintegration of the virions
      occurs in the cytoplasm and the L1/L2 proteins migrate to the nucleus via their
      nuclear localization signals.

PMID- 8525613
TI  - The vaccinia virus A38L gene product is a 33-kDa integral membrane glycoprotein.
AB  - The vaccinia virus gene A38L encodes a highly hydrophobic protein with amino acid
      similarity to mammalian integrin-associated protein (IAP). In this report we have
      identified the A38L protein of strain Western Reserve (WR), defined its membrane
      topology, and analyzed its role in virus production and virulence. An antiserum
      raised against an A38L peptide identified the A38L gene product as a 33-kDa
      protein which is expressed at low levels during virus infection. A serum from a
      rabbit previously infected with WR virus recognized the A38L protein, thus
      confirming that the A38L gene is expressed in vivo. Using a coupled in vitro
      translation/membrane-translocation system the 33-kDa protein was shown to be a
      membrane-associated and glycosylated form of a 29-kDa polypeptide precursor. The
      membrane topology of the A38L protein was defined by its glycosylation and
      protease sensitivity when associated with microsomal membranes. The N-terminal
      immunoglobulin-like variable domain was protected from exogenous protease and was
      therefore in the lumen of the vesicle, whereas the C-terminus was sensitive and
      therefore cytoplasmic. A38L deletion and revertant viruses were constructed and
      were used to study the involvement of A38L in virus assembly, release, and
      virulence. Deletion of the A38L gene caused a slight reduction in virus plaque
      size but did not affect the production of intracellular mature virus or
      extracellular enveloped virus particles in tissue culture cells nor the virulence
      of the virus in the murine intranasal model. The A38L protein therefore possesses
      similar sequence and membrane topology to the mammalian IAP protein but is not
      required for virus particle production or virulence.

PMID- 8525614
TI  - Hierarchal constitutive phosphorylation of the vesicular stomatitis virus P
      protein and lack of effect on P1 to P2 conversion.
AB  - In vitro reconstitution of a transcriptionally active VSV polymerase complex
      (P:L) reportedly requires phosphorylation of the N-terminal domain of P by CKII.
      Two constitutively phosphorylated sites have been implicated in this activation
      for both VSV Indiana and New Jersey serotype P proteins. We show here that, in
      contrast to New Jersey, the Indiana P protein is constitutively phosphorylated on
      three sites in vivo. The evidence rests on assessing the phosphorylation status
      of transfected P gene constructs containing all possible combinations of Ala
      substitutions at Ser60, Thr62, and Ser64. All mutants containing the T62A
      substitution showed a reduced level of phosphorylation and yielded no P-Thr.
      Surprisingly the S60A/S64A mutant behaved like the triple substitution and
      displayed no significant phosphorylation, while the S64A mutant yielded no P-Thr.
      Phosphorylation of Thr62 therefore depended on prior modification of Ser64. We
      also tested the ability of our mutant P proteins to convert to the more highly
      phosphorylated P2 species, a modification essential for transcription in the New
      Jersey serotype and thought to be carried out by an L-protein-associated kinase.
      All of our transfected mutant P proteins readily converted to P2 in the presence
      or absence of L cotransfection, and the latter had no significant effect on P
      phosphorylation. We conclude that VSV Indiana P protein differs in significant
      ways from New Jersey P. It is hierarchically and constitutively phosphorylated on
      a cluster of three sites, not two, suggesting that an additional kinase may be
      involved. Moreover, Indiana P1 to P2 conversion is independent of prior
      constitutive phosphorylation and does not require the presence of L protein.

PMID- 8525615
TI  - Cell type-dependent regulation of the activity of the negative regulatory element
      of the hepatitis B virus core promoter.
AB  - The Hepatitis B virus core promoter regulates the expression of the core protein,
      the precore protein, and the viral DNA polymerase. This promoter is
      transactivated by HNF4, a liver-enriched transcription factor, through an HNF4
      binding site located upstream of the core promoter. The transactivation activity
      of HNF4 on the core promoter is antagonized by a negative regulatory element
      (NRE) located upstream of the HNF4 binding site. While the NRE can effectively
      antagonize HNF4 to suppress the core promoter in HeLa cervical carcinoma cells,
      it has only a marginal suppressing activity on the core promoter in Huh7 hepatoma
      cells. By performing deletion-mapping experiments, we have found that the NRE
      contains at least three independent subregions named NRE alpha, NRE beta, and NRE
      gamma. Each of these three subregions possesses a weak suppressing activity, but
      together they generate a strong synergistic suppressing effect on the core
      promoter. The NRE gamma subregion is active in both HeLa and Huh7 cells and is
      bound by a protein factor slightly less than 130 kDa in molecular mass. The NRE
      alpha and NRE beta subregions are active in HeLa cells but not in Huh7 cells.
      Thus, the marginal suppressing effect of the NRE observed in Huh7 cells was
      mostly due to the activity of the NRE gamma subregion. No clear protein factor
      binding sites could be identified in the NRE alpha and NRE beta subregions when
      the HeLa nuclear extract was used for the DNaseI-footprinting analysis,
      indicating weak or no protein association with these two subregions in this cell
      type. However, extensive protein factor binding sites could be identified
      throughout the sequences of these two subregions when the Huh7 nuclear extract
      was used for the analysis. These results indicate that a different set of protein
      factors binds to the NRE alpha and NRE beta subregions in Huh7 cells and may
      account for the inactivity of these two subregions in this cell type. Thus, our
      results indicate that the cell type-dependent activity of the NRE is due to
      differential regulation of the activities of the NRE alpha and NRE beta
      subregions by the cell types. This regulation is most likely mediated by cell
      type-dependent protein factors.

PMID- 8525616
TI  - Interaction of bovine leukemia virus transactivator Tax with bZip proteins.
AB  - The bovine leukemia virus transactivator, BLV Tax, augments transcription from
      three imperfect 21-bp repeats in the viral transcriptional regulatory region.
      Each BLV 21-bp repeat contains a cAMP response element (CRE) in the center and
      unique 5' and 3' neighboring sequences which are crucial for the transcriptional
      activation by BLV Tax. Here we describe the interactions of recombinant BLV Tax
      with cellular bZip proteins. The recombinant BLV Tax, tagged at the carboxy
      terminus with a hexahistidine extension, was prepared by solubilization in 6 M
      guanidine hydrochloride and renaturation on the Ni(2+)-chelating Sepharose gel
      matrix. The renatured BLV TaxH6 activates the BLV LTR when introduced into HeLa
      cells by scrape loading. Furthermore, the purified BLV TaxH6 enhances binding of
      members of the CREB/ATF family of bZip proteins to CRE motifs by interacting with
      their bZip domains in vitro. Chemical cross-linking indicates that dimerization
      of bZip proteins such as CREB becomes greatly facilitated in the presence of BLV
      Tax. These results suggest that BLV Tax interacts directly with CREB/ATF-like
      factors to activate viral mRNA transcription.

PMID- 8525617
TI  - Tyrosine phosphorylation of phospholipase C-gamma 1 by vaccinia virus growth
      factor.
AB  - Vaccinia virus growth factor (VGF), a highly glycosylated polypeptide encoded in
      the genome of vaccinia virus, shares amino acid sequence homology and functional
      properties with cellular growth factors, EGF and TGF-alpha. Although the
      mitogenic activity of the purified or synthetic VGF suggested that the factor may
      be beneficial for viral replication by stimulation of host cell growth, neither
      the role in virus life cycle nor the step next to the EGF receptor activation had
      been firmly established. We found tyrosine-phosphorylations of PLC-gamma 1 and
      concomitant increase of the phosphoinositides level in the human epidermoidal
      A431 cells either treated with purified VGF or infected with vaccinia virus. In
      contrast to the wild-type virus, a VGF- mutant virus did not induce tyrosine
      phosphorylation of PLC-gamma 1. Phosphopeptide analysis indicated that the
      phosphorylation of the PLC-gamma 1 by VGF includes tyrosine residues identical to
      those phosphorylated by EGF. These results suggest that tyrosine phosphorylation
      of PLC-gamma 1, mediated by VGF, leads to activation of PLC-gamma 1 and a
      concomitant increase in phosphatidylinositol turnover.

PMID- 8525618
TI  - Interference with replication of two double-stranded RNA viruses by production of
      N-terminal fragments of capsid polypeptides.
AB  - It is possible to interfere with the replication of a number of plant RNA viruses
      by systemic production of viral capsid polypeptides or RNA-dependent RNA
      polymerases, or by production of untranslatable portions of viral plus strands or
      minus strands. Interference can occur by a number of mechanisms. We have
      discovered that the Saccharomyces cerevisiae double-stranded RNA viruses ScVL1
      and ScVLa, which exist as permanent persistent infections of their host cells,
      can be cured very efficiently by production of N-terminal fragments of their
      capsid polypeptides. These totiviruses produce only two polypeptides: a capsid
      polypeptide (Cap) and a Cap-Pol fusion polypeptide with RNA-dependent RNA
      polymerase activity. Three types of interference can be detected: interference
      due to overproduction of both Cap and Cap-Pol, interference due to overproduction
      of Cap (and consequent distortion of the Cap to Cap-Pol ratio), and interference
      due to negative complementation by N-terminal fragments of Cap. Some N-terminal
      fragments of Cap appear to be incorporated into viral particles, but only in the
      presence of a complete Cap protein. We postulate that incorporation of N-terminal
      fragments of Cap results in the formation of defective particles.

PMID- 8525619
TI  - Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the
      activation of the protein kinase that phosphorylates the elF-2 translation
      initiation factor.
AB  - The NS1 protein of influenza A virus binds not only to poly(A) and a stem-bulge
      region in U6 small nuclear RNA (snRNA), but also to double-stranded (ds) RNA.
      Binding assays with NS1 protein mutants established that the previously
      identified RNA-binding domain of the NS1 protein is required for binding to ds
      RNA as well as for binding to poly(A) and U6 snRNA. In addition, dsRNA competed
      with U6 snRNA for binding to the NS1 protein, consistent with both RNAs sharing
      the same binding site on the protein. As a consequence of its binding to dsRNA,
      the NS1 protein blocks the activation of the dsRNA-activated protein kinase (PKR)
      in vitro. This kinase phosphorylates the alpha subunit of eukaryotic translation
      initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of
      initiation of translation. Assays using purified PKR and purified elF2
      demonstrated that the NS1 protein blocks the dsRNA activation of PKR, and
      experiments using reticulocyte extracts showed that the NS1 protein blocks the
      inhibition of translation caused by dsRNA activation of PKR. The implications of
      these results for control mechanisms occurring in influenza virus-infected cells
      are discussed.

PMID- 8525620
TI  - Recurrence of WHV integration in the b3n locus in woodchuck hepatocellular
      carcinoma.
AB  - Frequent occurrence of woodchuck hepatitis virus DNA (WHV DNA) integration into
      or in proximity to myc oncogenes and in the win locus of cellular genome in
      woodchuck hepatocellular carcinomas (HCC) has been described by several authors.
      We report a further cellular locus as a recurrent target for WHV integration in
      woodchuck HCCs. A WHV DNA integration and its cellular flanking regions were
      cloned from a HCC developed in a chronically WHV-infected woodchuck. Sequence
      analysis showed integration of rearranged C, PreS1, and 5' truncated X regions of
      the WHV genome, located in a cellular locus previously described for WHV
      integration in another woodchuck HCC. The two integration sites are only about
      0.5 kb apart. In addition to Alu-like repeats and a gag-like coding region,
      previously described, we found several features of MAR (matrix attachment region)
      chromosomal sequences in the normal cellular locus, leading us to predict that
      part of it might be a previously unrecognized MAR.

PMID- 8525621
TI  - Cucumber mosaic cucumovirus antibodies from a synthetic phage display library.
AB  - Antibody fragments (scFv) that bind specifically to particles of cucumber mosaic
      cucumovirus (CMV) were obtained from a library which encodes a diverse array of
      synthetic antibody fragments, each displayed on the surface of filamentous
      bacteriophage. After four rounds of selection and enrichment, several clones were
      obtained which produced scFv that bound specifically to purified particles of CMV
      in ELISA. BstNI digestion of phagemid DNA resulted in the same restriction
      pattern for all clones. The nucleotide sequences of three of the clones showed
      that they belonged to the human VH1 family and that they had a complementarity
      determining region loop of 7 amino acids. Phage-displayed antibodies and soluble
      scFv secreted by these clones reacted with particles of CMV in sap from infected
      plants in ELISA. In immunoblotting tests, soluble scFv preparations reacted with
      SDS-denatured coat protein extracted from purified preparations of CMV isolates
      belonging to either subgroup I or II and also with protein extracted by SDS
      treatment of seeds harvested from naturally infected lupin plants. The results
      demonstrate the feasibility, and potential applicability, of recombinant antibody
      methods in plant pathology.

PMID- 8525622
TI  - Murine leukemia virus-induced neurodegeneration of rats: enhancement of
      neuropathogenicity correlates with enhanced viral tropism for macrophages,
      microglia, and brain vascular cells.
AB  - A highly neuropathogenic retrovirus, NT40, was generated by serially passaging an
      infectious molecular clone of Friend murine leukemia virus, FB29, through F344
      Fisher rats. NT40 induced severe neurological signs such as reflex abnormalities
      and ataxia within 4-6 weeks following neonatal inoculation. FB29 led to only very
      mild neurological dysfunctions with longer incubation periods. Pathological
      alterations were characterized by mild (FB29) to extensive (NT40) noninflammatory
      spongiform degeneration, mainly of brain-stem areas. Infectious center assays
      revealed that viral titers in brain tissues of NT40-infected rats were 100-fold
      higher than those of FB29-infected animals. Employing immunohistochemistry, in
      situ hybridization, and flow cytometry, NT40 was found to infect many endothelial
      cells of brain blood vessels and microglia, whereas FB29 infected only microglia
      and those to a lower extent. However, when isolated from adult diseased rats,
      microglial cells turned out in both cases to be nonproductively infected with
      either FB29 or NT40. Of peripheral organs, we found enhanced levels of NT40 in
      peritoneal macrophages but not in spleen, thymus, or serum when compared to FB29.
      Altogether these data suggest that an expanded cellular tropism within the CNS
      and elevated viral titers in macrophages and microglia correlated with
      enhancement of neuropathogenicity.

PMID- 8525623
TI  - Differentiation-dependent transcription of the epidermodysplasia verruciformis
      associated human papillomavirus type 5 in benign lesions.
AB  - Human papillomavirus type 5 (HPV 5) induces cutaneous lesions and persists in
      skin carcinomas of patients with epidermodysplasia verruciformis (EV). We
      investigated the expression pattern of HPV 5 in biopsies from benign skin lesions
      of EV patients by cDNA analysis and in situ hybridization. Nine different cDNAs
      could be generated from total RNA of one of these lesions by reverse
      transcription and PCR amplification with HPV 5-specific primers. We could
      identify two major splice donors: one was found in the E6-proximal part of the
      noncoding region (NCR), and the other just downstream of the first ATG codon of
      ORF E1. Each of the characterized transcripts was processed at one or the other
      donor site and the two corresponding leader exons were found in combination with
      both 3'-early and late exons. Two transcripts appear to be specific for EV
      associated papillomaviruses: one species might encode an E1--E2C fusion protein,
      and the other mRNA (NCR/E2) is probably encoding for the full-length E2 protein.
      According to the results of the cDNA analysis, riboprobes were designed for in
      situ hybridization experiments to study the cell differentiation-dependent
      expression of the different exons. Only the E7/E1 and E4 probes led to strong
      signals almost throughout the epithelium. The signals generated by the 5'-E2 and
      E1 probe increased with cell differentiation and were mainly confined to the
      nucleus. The NCR, E6, E7, L2, and L1 probes yielded more or less strong signals
      in the terminally differentiated epidermal layers. The difference in the cell
      differentiation-dependent expression of the 5'-early region exon (probe E7/1) and
      L2/L1 exons may point to a differentiation-dependent processing of transcripts.

PMID- 8525624
TI  - The varicella-zoster virus immediate-early 62 promoter contains a negative
      regulatory element that binds transcriptional factor NF-Y.
AB  - The varicella-zoster virus (VZV) immediate-early (IE) open reading frame 62
      (ORF62) promoter sequence contains a CCAAT box, located between positions -117
      and -113. Mutation of this motif resulted in a five-fold increase of promoter
      activity. In mobility shift assays, we demonstrated that NF-Y, a CCAAT box
      binding protein critical for the expression of diverse eukaryotic genes, binds to
      this motif. Thus, the VZV IE ORF62 promoter contains a negative regulatory
      element that binds the ubiquitous transcriptional factor NF-Y.

PMID- 8525625
TI  - Human papillomavirus type 11 E1--E4 and L1 proteins colocalize in the mouse
      xenograft system at multiple time points.
AB  - The most abundant viral mRNA species in HPV 11-infected tissue consists of two
      exons, joining a segment of open reading frame (ORF) E1 to ORF E4, potentially
      encoding the E1--E4 protein. The L1 ORF encodes the major capsid protein of HPV.
      Our previous studies demonstrated colocalization of the HPV 11 E1--E4 and L1
      proteins within the same cells of HPV 11-infected human foreskin implants grown
      in athymic mice (the mouse xenograft system) and removed 12 weeks after
      implantation. Prior studies have demonstrated E1--E4 transcripts early in
      infection and throughout the HPV 11-infected epithelium, while L1 transcripts are
      detected later, and in a subset of E1--E4 mRNA-positive differentiated epithelial
      cells. Therefore, E1--E4 protein may be produced at an earlier time point or in
      less differentiated cells than the L1 protein. To study these questions, athymic
      mice were implanted with HPV 11-infected human foreskin fragments. Mice were
      sacrificed at 1-week intervals beginning 2 weeks after implantation of tissue.
      The E1--E4 and L1 proteins colocalized to the same differentiated epithelial
      cells or to tight clusters of cells in differentiated epithelial layers of HPV 11
      infected implants. The E1--E4 and L1 proteins were first detected 4 weeks after
      implantation. E1--E4 protein was detected in the region of the cell membrane and
      cytoplasm, and never in the nucleus. L1 protein was only detected in the nucleus.
      Both proteins were detected in implants containing high viral copy numbers. No
      specific histologic changes were uniformly associated with detection of these
      proteins. The tight coupling of the E1-E4 and L1 proteins at multiple time points
      suggests that expression of both proteins is necessary to complete the virus life
      cycle.

PMID- 8525626
TI  - Multiple species of defective RNAs in plants infected with citrus tristeza virus.
AB  - Alemow (Citrus macrophylla) and sweet orange (C. sinensis) plants infected,
      respectively, with several Israeli and Florida isolates of the citrus tristeza
      virus (CTV) were found to contain multiple species of RNA molecules with features
      similar to defective-interfering RNAs. Northern blot hybridizations of dsRNAs
      extracted from serial passages of the Israeli VT isolate (CTV-VT) and from
      different plants infected with a single source of inoculum showed considerable
      variation both in the presence and in the relative abundance of the defective RNA
      (D-RNA) bands. The D-RNA molecules were found to be encapsidated in the CTV
      particles. Sequence analysis of two VT D-RNA molecules of 2.7 and 4.5 kb revealed
      that they were composed of two regions corresponding to 1818 and 4036 nucleotides
      from the 5' and 938 and 442 nucleotides from the 3' termini of the CTV-VT genomic
      RNA, respectively. A short (ca. 0.8 kb) nonencapsidated single-stranded positive
      sense RNA species was also found in infected plants. This ssRNA, which copurified
      with dsRNAs, was shown by hybridization to encompass the 5'-terminal part of the
      CTV genome and might have an extensive secondary structure.

PMID- 8525627
TI  - 3' Terminal putative stem-loop structure required for the accumulation of
      cymbidium ringspot viral RNA.
AB  - Defective interfering (DI) RNA of cymbidium ringspot tombusvirus (CymRSV) was
      used to identify the cis-acting nature of the last 77-nt sequence of the viral
      genome which is required for DI RNA accumulation. The 3'-terminal cis-essential
      domain of both genomic and DI RNAs can be folded into a stable stem-loop
      structure composed of three hairpins and two short non-base-paired regions. None
      of the three conserved stem-loops can be deleted without abolishing the
      infectivity of DI RNA. Similarly, those mutants in which base-paired stem regions
      were disrupted by single-, double-, or triple-base substitutions were unable to
      replicate. However, when the original structures were reconstructed by
      compensatory mutations the viability of the molecules was also restored. Limited
      mutation (1 or 2 nt) in the non-base-paired region did not show any significant
      effect on viral replication. Our results strongly suggest that the proposed
      structure for the 3' terminus of the viral genome is very important for viral RNA
      replication. It is very likely that the function of this structure is to promote
      the minus-strand synthesis of CymRSV DI RNA. Evidence is provided that the
      proposed 3'-terminal structure is relevant not only for CymRSV DI but for genomic
      RNA as well.

PMID- 8525628
TI  - DNA rearrangements impairing BK virus productive infection in urinary tract
      tumors.
AB  - Eighty-nine tissue specimens from the urinary tract and prostate were analyzed
      for the presence and physical state of BK virus (BKV) DNA. Large T antigen gene
      sequences were amplified by PCR from prostate, kidney, ureter, and bladder with
      prevalences ranging from 50 to 83%. Sequence analysis of PCR products from the
      high variable BKV regulatory region showed that these tissues contained a new BKV
      strain (URO1). URO1 presents a duplication of part of the 68- and 39-bp elements
      of the viral enhancer, and a 68-bp deletion spanning part of the 39- and 63-bp
      enhancer elements. Six neoplastic specimens (11.5%), but none of the control
      tissues, contained viral DNA in amounts detectable by Southern blot hybridization
      (P < 0.05). The tumors positive by Southern blot hybridization harbored
      rearranged and/or integrated DNA sequences whose size was apparently incompatible
      with assembly into a viral particle. A full-length, macroscopically intact BKV
      early region was amplified from these tumors by PCR. The restriction pattern of
      the rearranged sequences was simple, suggesting that tumors were clonal and that
      DNA rearrangement occurred at an early stage of neoplastic initiation or
      progression.

PMID- 8525629
TI  - Sequence analyses and antigenic epitope mapping of the putative RNA-directed RNA
      polymerase of five U.S. bluetongue viruses.
AB  - We determined the complete nucleotide sequences of the cognate L1 double-stranded
      RNA segments of bluetongue virus (BTV) serotypes 2, 11, 13, and 17, which encode
      the putative RNA-directed RNA polymerase VP1. Each L1 gene contained 3944
      nucleotides and was 10 bases shorter than the previously reported L1 gene of BTV
      10. A single open reading frame which could encode the reported VP1 protein, 1302
      amino acids in size, began with an initiation codon at nucleotides 12-14 and a
      termination codon at nucleotides 3918-3920. Analyses of the nucleotides of L1
      genes and the deduced amino acid sequences of VP1 proteins of the five U.S. BTV
      serotypes indicated that the most recently isolated BTV-2 serotype from Florida
      was more distantly related than BTV-10, 11, 13, and 17, which were isolated
      primarily in the western U.S.A. The results are consistent with our hypothesis
      that BTVs-10, -11, -13, and -17 are derived from a single and common gene pool,
      and that BTV-2 belongs to a second, distinct gene pool. These genetic
      distinctions also reflected well with the known geographic distribution of the
      five U.S. BTV serotypes in North America. This putative RNA-directed RNA
      polymerase (149 KDa) was a basic protein, and the deduced amino acid sequences of
      the VP1 proteins contained seven highly conserved hydrophobic domains and many
      other sequence motifs which were also found in other known RNA polymerases. Four
      immunodominant but linear antigenic epitopes conserved among the VP1 of five U.S.
      BTVs were also been identified and mapped using monospecific oligoclonal
      antibodies.

PMID- 8525630
TI  - Dimerization of the human papillomavirus E7 oncoprotein in vivo.
AB  - We have used a yeast two-hybrid system to show that human papillomavirus E7
      proteins can form oligomeric complexes in vivo. The carboxyl-terminal cysteine
      rich metal-binding domain is critical for this activity although amino-terminal
      sequences also contribute to oligomerization. Our experiments also reveal that E7
      possesses an intrinsic transcription activation activity in yeast, which resides
      in the amino terminus of the protein.

PMID- 8525631
TI  - Differences in the role of glycoprotein C of HSV-1 and HSV-2 in viral binding may
      contribute to serotype differences in cell tropism.
AB  - Heparan sulfate serves as a receptor for several herpesviruses. For herpes
      simplex virus 1 (HSV-1), pseudorabies virus, and bovine herpesvirus 1,
      glycoprotein C homologues have been shown to mediate the binding to cell-surface
      heparan sulfate. It has been assumed that glycoprotein C of HSV-2 (gC-2) plays a
      similar role in HSV-2 entry, but this has not been established experimentally. We
      first determined, using heparin-affinity chromatography, that gC-2 is a heparin
      binding glycoprotein. To examine the role of gC-2 in HSV-2 infection, we
      constructed a gC-2 deletion mutant, HSV-2(G)gC-. In contrast to results obtained
      for the other alpha herpesviruses, we found that the HSV-2(G)gC- virus showed no
      loss in specific binding activity (particles bound/cell) or specific infectivity
      (PFU/particle) compared to the parental wild-type virus. Moreover, while gC-1
      mutants show a marked lag in the rate of viral penetration, the gC-2-deletion
      virus did not. We did find that gC-2, like gC-1, protects virus from complement
      mediated neutralization. These results suggest that, in contrast to HSV-1, gC-2
      does not play the key role in viral binding. The major role of gC-2 may be to
      protect virus from complement-mediated neutralization. We speculate that serotype
      differences in the contribution of gC to viral binding may contribute to serotype
      differences in cell tropism.

PMID- 8525632
TI  - Hemagglutinin-neuraminidase of human parainfluenza 3: role of the neuraminidase
      in the viral life cycle.
AB  - The function of neuraminidase in the life cycle and pathogenesis of human
      parainfluenza virus type 3 (HPF3) was studied by analyzing a variant of HPF3 that
      has decreased neuraminidase enzymatic activity. The variant virus is more
      fusogenic than the wild-type virus during an acute infection. Cloning and
      sequencing of the fusion (F) and hemagglutinin-neuraminidase (HN) genes from this
      variant revealed a single amino acid change in the HN protein and no alterations
      in the F protein sequence. Analysis of the growth properties of this variant
      revealed a delay in release of virus particles into the supernatant. Addition of
      exogenous neuraminidase to the culture resulted in increased release of
      infections viral particles, suggesting that the viral neuraminidase is important
      for release of HPF3 from the infected cell surface. In addition, the behavior of
      the variant virus during high-multiplicity infection and in the presence of
      exogenous neuraminidase provided evidence that the neuraminidase of HPF3
      determines the outcome of viral infection (cytopathic versus persistent) in cell
      culture.

PMID- 8525633
TI  - Molecular interactions between HTLV-1 Tax protein and the NF-kappa B/kappa B
      transcription complex.

PMID- 8525634
TI  - Stimulation of human papillomavirus type 1a DNA replication by a multimerized AT
      rich palindromic sequence.
AB  - Replication of most papillomaviruses requires the viral E1 and E2 proteins and an
      origin of replication containing the E1 and E2 binding sites. In the case of
      human papillomavirus type 1a (HPV-1a), the E1 protein alone is sufficient for DNA
      replication although the E2 protein significantly stimulates replication. We have
      further analyzed the role of cis-acting sequences and the E1 and E2 proteins in
      HPV-1a replication. Previous studies have shown that a 60-bp region lacking the
      E2 binding sites but containing an imperfect 16-bp AT-rich palindrome
      corresponding to the putative E1 binding site contains the minimal origin of
      replication (ori). Using a transient replication assay, we demonstrate that
      duplication of this 60-bp region causes a severalfold increase in replication.
      Synthetic oligonucleotides containing a 39-bp region centered around the above
      palindromic sequence supported only low-level replication in the presence of
      either E1 alone or both E1 and E2, but replication was significantly increased in
      the presence of multiple copies of this sequence. Plasmids containing a 19-bp
      sequence which includes the AT-rich palindrome failed to replicate, but multiple
      copies of this region supported replication in the presence of both E1 and E2 to
      significant levels. The results presented indicate that the HPV-1a E1 protein is
      capable of recruiting all the cellular factors required for replication. Our
      results also suggest that multimerization of the AT-rich palindromic sequence may
      result in a significant increase in the recruitment of the E1 protein to the
      origin, thereby stimulating replication. This increased targeting of the E1
      protein to the origin containing multiple copies of the putative E1 binding site
      may be functionally similar to the targeting of E1 to the origin by E2.

PMID- 8525635
TI  - Tissue-specific gene expression from Mo-MLV retroviral vectors with hybrid LTRs
      containing the murine tyrosinase enhancer/promoter.
AB  - Transcriptional tissue specificity was engineered directly into Moloney Murine
      Leukaemia Virus (Mo-MLV)-derived retroviral vectors by replacing the viral
      enhancer in the 3' long terminal repeat (LTR) with two different lengths (2.5 kbp
      or 769 bp) of the murine tyrosinase promoter/enhancer. The hybrid tyrosinase-LTR
      was transferred to the proviral 5' LTR following viral packaging and infection of
      target cell lines. Hybrid tyrosinase-LTR-driven IL-2 production was barely above
      background levels in infected nonmelanoma cell lines containing intact provirus,
      whereas infected melanoma cell lines expressed high levels of IL-2 and the larger
      tyrosinase promoter/enhancer fragment directed higher levels of transgene
      expression. By replacing the viral enhancer with the tyrosine promoter/enhancer
      sequences, promoter interference effects which we have previously observed when
      the tyrosinase promoter was included as an internal promoter within a similar
      retroviral vector were effectively abolished. Our data show that the hybrid
      tyrosinase-LTR behaves as a tightly regulated melanocytic-specific regulatory
      element when embedded in an enhancer-deleted Mo-MLV LTR. The use of other
      heterologous cellular promoter/enhancer elements in similar vectors should allow
      the development of simpler, targeted retroviral vectors for the expression of
      genes in selected cell types and may eventually provide for the development of
      safer, more efficient vectors for use in human gene therapy.

PMID- 8525636
TI  - Subcellular immunolocalization of the coat protein of two potexviruses in
      infected Chenopodium quinoa.
AB  - The production of coat protein is necessary for cell-to-cell transport of
      potexviruses in plants. To investigate the role of coat protein in the movement
      process, the intracellular distribution of coat protein in tissues infected with
      either of two potexviruses was studied using immunocytochemical procedures. We
      report that coat protein antigens are associated with the plasmodesmata of
      infected cells.

PMID- 8525637
TI  - Strain variability and localization of important epitopes on the major structural
      protein (VP2) of infectious pancreatic necrosis virus.
AB  - Infectious pancreatic necrosis virus (IPNV), a birnavirus, is an important
      pathogen in fish farms. Analyses of viral proteins showed that VP2 is the major
      structural and immunogenic polypeptide of the virus. All neutralizing monoclonal
      antibodies (mAbs) against IPNV are specific to VP2 and bind to continuous or
      discontinuous epitopes. In order to determine which parts of the protein are
      involved in antigenic variations, five IPNV strains were sequenced over the VP2
      coding region. Comparison of the sequences obtained with three previously
      published strains revealed a central variable domain (positions 183 to 335) which
      encompasses two hydrophilic hypervariable segments. Viral mutants which escaped
      neutralization were then selected with anti-VP2 mAbs directed against
      discontinuous epitopes. Sequencing of three mutants revealed a single amino acid
      mismatch in each of them. All of these substitutions occurred in the
      hypervariable segments, suggesting that these regions are involved in the
      formation of a discontinuous epitope. Finally, expression of different truncated
      VP2s in Escherichia coli allowed localization of the binding site for
      neutralizing mAbs which recognize continuous epitopes. One of these mAbs bound to
      the region adjacent to the C-terminus of the variable domain of VP2, while two
      others reacted with the central and C-terminal parts of the variable domain. No
      antibody reacted with the N-terminus of VP2. These results suggest that the
      variable domain of VP2 and the 20 adjacent amino acids of the conserved C
      terminal part are the most important in inducing an immune response for the
      protection of animals.

PMID- 8525638
TI  - Assembly of SIV virus-like particles containing envelope proteins using a
      baculovirus expression system.
AB  - The requirements for SIV particle assembly and envelope incorporation were
      investigated using a baculovirus expression system. The Pr56gag precursor protein
      expressed under control of the polyhedrin promoter (pPolh) produced high levels
      of immature retrovirus-like particles (VLP) upon expression in Sf9 insect cells.
      To determine the optimal conditions for envelope protein (Env) incorporation into
      VLP, two recombinant baculoviruses expressing the SIV envelope protein under
      control of a very late pPolh or a hybrid late/very late capsid/polyhedrin
      (Pcap/polh) promoter and a recombinant expressing a truncated form of the SIV
      envelope protein (Envt) under the hybrid Pcap/polh promoter were compared. We
      have observed that utilization of the earlier hybrid promoter resulted in higher
      levels of Env expression on the cell surface and its incorporation into budding
      virus particles. We have also found that the Envt protein is transported to the
      cell surface of insect cells and incorporated into VLP more efficiently than full
      length Env. In addition, we examined the effect of coexpression of the protease
      furin, which has been implicated in the proteolytic cleavage of the Env precursor
      gp160 in mammalian cells. Coexpression of furin in insect cells resulted in more
      efficient proteolytic cleavage into gp120 and gp41, and the cleaved proteins were
      incorporated into VLP.

PMID- 8525639
TI  - Biochemical and genetic analyses of the interaction between the helicase-like and
      polymerase-like proteins of the brome mosaic virus.
AB  - Replication of the three positive-strand genomic RNAs of brome mosaic virus
      requires the activities of the helicase-like 1a and the polymerase-like 2a
      proteins. One hundred fifteen amino acids of the 2a N-terminus and the 1a
      helicase-like region of over 50 kDa are both necessary and sufficient for 1a-2a
      interaction. Requirement of the large size of the 1a helicase-like domain
      suggests that higher order structures might be necessary for the protein's
      interaction with 2a. To explore the structural properties of 1a, we used limited
      proteolysis of in vitro-translated 1a protein. Treatment of 1a and its deletion
      derivatives with papain or trypsin revealed that the C-terminal helicase-like
      segment of approximately 50-60 kDa is highly resistant under our assay conditions
      to proteolysis, while the N-terminus is rapidly degraded. All tested mutations in
      the helicase-like region that renders this region protease-sensitive have
      previously been found to be defective for RNA replication in vivo. To complement
      the in vitro studies, we examined the interaction of the 1a helicase-like domain
      and the 2a N-terminus in yeast using the two-hybrid system. Mutations previously
      known to disrupt 1a-2a interaction also prevented interaction in yeast.
      Furthermore, results from two-hybrid analysis suggest that the structural domain
      mapped in vitro is important for 1a-2a interaction. Finally, we found that the
      helicase-like proteins of three other tripartite RNA viruses also contain
      equivalently located protease-resistant domains.

PMID- 8525640
TI  - Functional and molecular characterization of African swine fever virus mutants
      resistant to phosphonoacetic acid.
AB  - African swine fever virus (ASFV) growth and plaque formation were inhibited by
      phosphonoacetic acid (PAA) concentrations of 200 micrograms/ml or more. One
      spontaneous mutant and two mutants isolated from mutagenized virus were resistant
      to PAA inhibition and showed practically normal viral DNA synthesis in the
      presence of PAA. DNA polymerase activity present in the cytoplasmic fraction from
      cells infected with the mutants required 10-fold higher concentrations of PAA for
      inhibition compared to equivalent inhibition of the wild-type enzyme. Like wild
      type virus, the PAA-resistant mutants were resistant to inhibition by
      aphidicolin. Marker rescue analysis with mutant DNA fragments covering different
      regions of the ASFV DNA polymerase gene mapped the mutations within a fragment
      which was cloned and sequenced. A single nucleotide and amino acid change was
      assigned to each mutant. Two of the PAA-resistant mutations lie within the highly
      conserved region II common to alpha-like DNA polymerases, which has been
      implicated in pyrophosphate binding and probably also in dNTP binding. The other
      mutation was localized to within a region of moderate homology among viral DNA
      polymerases close to one of the motifs allegedly considered as constituting the
      3'-5' exonuclease active site.

PMID- 8525641
TI  - Defective point mutants of the encephalomyocarditis virus internal ribosome entry
      site can be complemented in trans.
AB  - Point mutations were introduced at random into cDNA corresponding to nucleotides
      260-833 of the encephalomyocarditis virus (EMCV) 5' noncoding region. This region
      contains the internal ribosome entry site (IRES). The mutations were identified
      by sequence analysis and the effect on the activity of the IRES was determined
      using in vitro translation reactions in rabbit reticulocyte lysate. Significantly
      defective mutants each contained multiple point mutations. These mutants were
      constructed into a dicistronic mRNA expression plasmid and the activities of the
      mutant IRES elements were determined using the vaccinia virus/T7 RNA polymerase
      transient expression system in vivo. The most severely defective of these mutants
      displayed about 5% of wild-type activity. The activities, relative to wild type,
      of these mutant IRES elements determined using in vitro and in vivo assays were
      similar. Two deletion mutants, lacking sequences from the 5' terminus to nt 411
      and 484, were also constructed. Each of these deletions inactivated the IRES in
      vivo (to less than 1% of wild-type activity). Coexpression within cells of the
      wild-type EMCV IRES, either alone or linked to another coding sequence, enhanced
      the activity of each of the defective IRES elements except that deleted to nt
      484. The results are consistent with a model in which different regions of the
      IRES participate in a discontinuous transfer of an initiation complex to the 3'
      end of the IRES element for initiation of protein synthesis to occur.

PMID- 8525642
TI  - VP1 and VP2 capsid proteins of Theiler's virus are targets of H-2D-restricted
      cytotoxic lymphocytes in the central nervous system of B10 mice.
AB  - Resistance to Theiler's virus-induced demyelination maps genetically to the MHC
      class I D region and is associated with up-regulation of class I products and the
      presence of MHC-restricted virus-specific cytotoxic CD8+ T cells in the CNS. To
      determine the targets of the cytotoxic response, transfected C57SV (Kb, Db) cells
      expressing LP (including the leader peptide, VP4, VP2, and VP3 coding sequences),
      VP4 (including the leader peptide and VP4), VP2, VP3, VP1, or RP (including P2
      and P3) were generated. CNS-infiltrating lymphocytes obtained from virus-infected
      B10, B10.K (Kk, Dk), B10.RBF (Kb, Df). B10.RFB3 (Kf, Db), and B10.RBQ (Kb, Dq)
      mice were used as effectors. Specific cytotoxicity to the capsid proteins encoded
      in the LP construct, VP2 and VP1, was demonstrated to be H-2Db region restricted
      and was mediated by CD8+ T cells. No Kb-restricted virus-specific cytotoxicity
      response was observed. No specific cytotoxic response against RP-encoded proteins
      was observed in the CNS of B10 mice. Therefore, both VP1 and VP2 are targets for
      an H-2D-restricted cytotoxic immune response against Theiler's virus infection in
      the CNS of infected resistant B10 mice.

PMID- 8525643
TI  - [Lead, cadmium and mercury carry-over to meat products by spices and condiments].
AB  - The lead and cadmium contents of 50 species and 19 condiments were investigated
      by means of flameless atomic absorption spectrophotometry. Mercury contents were
      determined by cold vapor atomic absorption method including amalgamation. The
      mean concentrations of lead, cadmium, and mercury were 0.470 mg/kg, 0.080 mg/kg,
      and 0.005 mg/kg, respectively. By using the detected levels of these three heavy
      metals in model calculations only a small carry-over of lead, cadmium, and
      mercury in meat products by species and condiments can be assumed.

PMID- 8525644
TI  - Characterization of trypsin immobilized on oxirane-acrylic beads for obtaining
      phosphopeptides from casein.
AB  - The aim of the study was to characterize the proteolytic properties of
      immobilized trypsin for obtaining phosphopeptide-rich fractions from casein.
      Trypsin was covalently bound to oxirane-acrylic beads. After incubation for 48 h
      immobilization degrees of about 85% were achieved. 20% of the immobilized enzyme
      exhibited no activity towards the substrate N-benzoyl-L-arginine ethyl ester.
      Compared with homogeneous catalysis with the soluble enzyme a 25% lower degree of
      proteolysis was calculated and a modified peptide pattern of the resulting
      proteolysates established. A caseinophosphopeptide (CPP) from alpha s1-CN (59-79)
      was not detectable after incubation with the carrier-bound enzyme. At a substrate
      concentration (S) of 15% (w/w) substrate saturation of the enzyme (E) was
      achieved. Increasing the substrate concentration to 20% (w/w) decreased the
      conversion rates (content of soluble amino-N) and the liberation of CPPs.
      Proteolysis of small (1% w/w) and partly also large (20% w/w) substrate
      concentrations (E/S = 1/100) is subject to changed kinetic conditions. The same
      was true for small and large enzyme concentrations (S = 5% w/w). Compared with
      enzyme saturation (E/S = 1/50), lack of enzyme (E/S = 1/800) led to a
      disproportional decrease in the proteolysis rate and to a markedly decreased
      content of hydrophobic peptides in the resulting proteolysates. Increasing the pH
      from 7.8 to 8.8 and the temperature from 37 degrees to 47 degrees C caused only a
      slight increase in conversion rates, but an overproportional liberation of CPPs
      (pH 8.8 = + 47%, 47 degrees C = +89%), in particular from beta-casein. Repeated
      use of immobilized trypsin resulted after nine runs in a loss in proteolytic
      activity and in CPP yields of approximately 25%, while the peptide pattern of the
      proteolysates remained qualitatively unchanged. Light microscopy shows that the
      oxirane-acrylic beads disintegrate to a large extent after nine repetitions.

PMID- 8525645
TI  - [Assessment of individual iodine intake by the adult population in the Potsdam
      region on the basis of sea fish and iodized salt consumption].
AB  - Iodized salt has a high acceptance in the Potsdam region: 82% of the interviewed
      people use iodized salt, 13% do not use it, and only 5% of the probands were not
      able to make any statements. The current average iodine intake for adults is 76
      micrograms/day. Only 5% of the adult population has an iodine intake of more than
      100 micrograms/day. An efficient elimination of iodine deficiency in Germany
      requires a broad usage of iodized salt in the food industry.

PMID- 8525646
TI  - Plasma and whole blood taurine concentrations respond differently to taurine
      supplementation (humans) and depletion (cats).
AB  - In the present study the relationship between plasma and whole blood taurine was
      examined under normal physiological circumstances in humans and cats. In
      addition, the effect of taurine supplementation on plasma and whole blood taurine
      was evaluated in humans and the depletion of taurine pools after a taurine
      deprived diet was studied in cats. The normal plasma taurine concentration in
      humans was 44 +/- 8 mumol/L and the whole blood taurine concentration was 227 +/-
      35 mumol/L. Under normal physiological conditions plasma and whole blood taurine
      were not correlated (r = 0.092). Plasma taurine responded rapidly to dietary
      supplementation in humans or the taurine depletion in cats. In contrast, the
      whole blood taurine pool was more inert and varied only under extremes of
      depletion (cats) or sustained taurine supplementation.

PMID- 8525647
TI  - [Thermogenesis and energy utilization of olive oil and fish oil in a model study
      with sows].
AB  - An animal model experiment was conducted with nine adult sows to study the effect
      of olive oil and fish oil (40% polyunsaturated fatty acids) on thermogenesis
      compared to wheat starch as control. The treatments were given to each animal
      according to a latin square design. The basal diet (20 g DM/kg W0.75) was mainly
      based on barley and soybean meal, and matched 60% of the ME requirements with all
      the other nutrients meeting maintenance requirements. The isoenergetic
      supplements amounted to 176 kJ gross energy per kg W0.75 and day. During each
      experimental period a complete energy balance was recorded for each animal using
      indirect calorimetry technique (RQ-method) as well as the carbon-nitrogen-balance
      technique. The treatments did not influence the digestibility of the rations.
      Digestibility of energy and of carbon averaged 83.4% and 83.3%, respectively. All
      three supplements were nearly completely digested as calculated by the difference
      method. Fish oil increased urine energy and decreased CH4 production, the shifts,
      however, were in absolute terms very small. The mean O2 consumption was 1,002 l/d
      showing no significant treatment effects. CO2 production was lowered with olive
      oil by 10%, and with fish oil by 13% compared to the starch diet. The daily heat
      production was 20.95, 20.72, and 20.04 MJ when starch, olive oil or fish oil was
      given. Corrected for equal energy retention the difference of thermogenesis
      between olive oil and starch was -0.4 MJ/d, and between fish oil and starch -1.2
      MJ/d. These differences corresponded to a relation of starch:olive oil:fish oil =
      1:0.95:0.86. The relation between starch and olive oil reflected exactly the
      theoretical expectation, calculated from the ATP regeneration by oxidation of
      both nutrients. When fish oil was added, the daily heat production was lower than
      theoretically calculated, which might be interpreted as an effect on the
      metabolic rate in general rather than especially on the efficiency of ATP
      formation from fish oil oxidation. In any case, there was no hint of a
      facultative thermogenesis induced by the oils.

PMID- 8525648
TI  - [Effect of olive oil and fish oil on parameters of lipids and antioxidants in
      hyperlipoproteinemia].
AB  - In 56 patients with HLP (40 with hypertriglyceridemia and mixed HLP respectively
      and 16 with hypercholesterolemia), changes in the lipid state and in the
      parameters of the antioxidative potential before and after a 4-week olive-oil
      phase, and after 8-, 20- and 32-week intakes of salmon-oil capsules were
      determined. The treatment with salmon-oil led to a decrease of triglycerides in
      patients with hypertriglyceridemia and mixed HLP respectively, on the other hand,
      it led to an increase of cholesterol in hypercholesterolemia. The increase of
      malondialdehyde as measure of lipid peroxidation in both patient groups
      underlines the necessity of a substitution of antioxidants. Further
      investigations are necessary before wide use of fish-oil capsules can be
      recommended, especially to avoid side-effects.

PMID- 8525649
TI  - [Intestinal absorption of homologous and heterologous immunoglobulin G in newborn
      calves].
AB  - Studying the prophylactic effects of specific yolk antibodies against diarrhea in
      newborn calves, also the intestinal absorption of unspecific heterogeneous avian
      antibodies as well as their effects on the uptake of maternal bovine colostral
      antibodies (bIgG) was investigated. Two groups of newborn calves received egg
      powder (16 g or 8 g per day) for the first 10 days of their life beginning with
      the first meal. A third group was kept as a control without any egg powder in
      their diet. Blood samples (5 to 10 calves per sampling time) were taken from 123
      calves at 6, 12, 24, 48, or 96 h postnatally. With both doses the highest chicken
      IgG (cIgG) levels (3.1 micrograms resp. 1.2 micrograms per ml serum) have been
      measured 12 h after birth. These concentrations decreased continuously to the
      levels of 1.1 micrograms resp. 0.2 micrograms cIgG per ml serum at 96 h
      postnatally. The uptake into blood at 6 h postnatally has roughly been estimated
      as approximately 23% (bIgG) and 7% resp. 6% (cIgG) of the IgG dosages given with
      the first meal. The time-course (6 to 96 h) of the bIgG level in blood was quite
      stable, plateauing already after 6 h at a mean of 5.9 mg per ml serum.
      Significant differences between the bIgG levels of calves with yolk antibodies in
      their diet (6.2 resp. 6.1 mg bIgG per ml serum) and those of the control group
      (5.4 mg per ml serum) could not be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525650
TI  - [Adulteration of food and luxuries and the origins of uniform state food
      legislation in Germany].
AB  - During the last two decades, there has been an increasing movement in Germany to
      protect the natural environment from dangerous substances. This has renewed a
      growing common interest in government food control. This contribution ask the
      question of how this food legislation as a part of the general food and health
      policy in Germany came into being, and which promoting as well as inhibiting
      determinants in this scope could be observed. These statements are based partly
      on results of a project of the German National Research Council (Deutsche
      Forschungsgemeinschaft) in which the author investigates the change of food
      habits under the impact of industrialization and urbanization since the last
      century in a larger historical perspective and in a quantitative and qualitative
      manner with the help of current sources.

PMID- 8525651
TI  - Addition of interleukin 12 to low dose interleukin 2 treatment improves antitumor
      efficacy in vivo.
AB  - Interleukin 12 (IL-12) enhances lysis mediated by NK- and lymphokine activated
      killer (LAK) cells. It also causes proliferation of IL-2 stimulated T and NK
      cells in vitro. For these IL-2 complementing properties murine pulmonary
      metastases of a coloncarcinoma line were treated with IL-12 and IL-2 or with the
      individual agents. Results were compared to sham treated controls. IL-2 alone
      mediated significant tumor reduction but provoked pulmonary edema and
      concomittand toxicity, graded in three steps. IL-12 combined with an IL-2 dose
      reduced by 81% still resulted in significant antitumoral activity. Toxicity,
      however, was not discernable from sham treated controls. IL-12 thus appears as an
      attractive cytokine for combination with IL-2 in antitumor therapy. Particularly
      treatment of tumors, like gastrointestinal tract cancers, so far mainly resistant
      to cell mediated antitumor therapy, might profit from this approach.

PMID- 8525652
TI  - Tumor-necrosis-factor and interleukin-6 response of peripheral blood monocytes to
      low concentrations of lipopolysaccharide in patients with alcoholic liver
      disease.
AB  - Plasma levels of endotoxin and tumor necrosis factor alpha (TNF alpha) and the
      cytokine response of isolated monocytes were examined in chronic alcohol abusers
      with various degrees of liver disease. In 35 patients - 19 with alcoholic fatty
      liver (AF), 7 with alcoholic hepatitis (AH), 9 with cirrhosis (AC) - and in 15
      healthy controls (HC), plasma levels of endotoxin were measured in the limulus
      assay, and plasma TNF alpha in an immunoassay. The cytokine response of monocytes
      stimulated in vitro with low doses of endotoxin (range: 25 pg/ml to 2.5 ng/ml)
      was determined in a cytolytic TNF bioassay and in TNF alpha and interleukin-6 (IL
      6) immunoassays. All patient groups had elevated plasma endotoxin levels, whereas
      plasma TNF alpha was elevated only in AC (43.1 +/- 15.2 vs. HC: 5.0 +/- 1.1
      pg/ml). Monocytes from all patient groups released increased amounts of bioactive
      TNF: AF 5.39 +/- 1.70, AH 7.10 +/- 3.28, AC 2.44 +/- 0.54 vs. HC 1.21 +/- 0.30
      ng/ml (stimulation with 2.5 ng/ml endotoxin over 3 hrs.). Similar results were
      obtained in the TNF alpha immunoassay. Increased release of IL-6 from monocytes
      was shown only for AF, while values in AC were comparable to those in HC. These
      data confirm that endotoxemia is frequent in chronic alcoholics. In concert with
      an increased cytokine response of the monocyte/macrophage system, endotoxemia
      might contribute to the pathogenesis of alcoholic liver disease.

PMID- 8525653
TI  - Smoking as a risk factor for duodenal ulcer relapse. RUDER Study Group.
AB  - This study reports the influence of smoking on the two-year relapse rate of
      duodenal ulcers under treatment with ranitidine. 1899 patients with a healed
      duodenal ulcer received 150 mg ranitidine daily for one year, 1671 patients for
      two years. During this time period 23.4% of smokers relapsed compared with 26.3%
      of ex-smokers and 18.0% of non-smokers. The difference between smokers and ex
      smokers versus non-smokers was statistically significant. There were
      significantly fewer relapses among smokers who stopped smoking (14.2%) compared
      with smokers who continued to smoke (25.2%) during maintenance treatment. These
      results show that continued and past smoking significantly increase the two-year
      relapse rate of duodenal ulcers during maintenance treatment with ranitidine.

PMID- 8525654
TI  - Gastrointestinal problems in airline crew members.
AB  - The presence of intestinal and extraintestinal symptoms was investigated by a
      symptom questionnaire in crew members (n = 190) - and as controls in age and sex
      matched ground based administrative employees (n = 100) - of a charter carrier
      and was related to the actual flight schedule of the flying staff during one
      month. In addition, health and illness behaviors and personal, job and life
      satisfaction were assessed and related to symptom scores and flight schedules.
      Flying staff did report significantly more dyspeptic symptoms than did ground
      staff, and this was found mainly with long-distance flying, since staff with
      short-haul experience only did not report as much upper intestinal complaints.
      Also, cabin crew reported significantly more intestinal symptoms than did cockpit
      members, and part of the upper GI symptoms could be explained by different eating
      behaviors, specifically more fibre intake in flying staff. With increasing
      intestinal symptom frequency, doctor visits and sick-days increased, and
      satisfaction with job and personal life decreased. Flying staff had, however,
      more awareness of the importance of health behaviors. It is concluded that
      frequent flying specifically on long distances may result in increased intestinal
      symptoms, presumably due to time-shift.

PMID- 8525655
TI  - Measurement of transit disorders in different gastrointestinal segments of
      patients with diabetes mellitus in relation to duration and severity of the
      disease by use of the metal-detector test.
AB  - The existence of gastrointestinal transit disorders in other intestinal segments
      beside the stomach in Type-1 diabetes mellitus (DM) and occurrence in Type-2 DM
      and in uremia has yet been confirmed only in few studies. Eleven healthy
      volunteers, 34 patients with Type-1, 32 patients with Type-2 DM in different
      stages of their disease and 34 non-diabetic patients with endstage-renal disease
      were investigated by use of the metal detector test. Patients were divided in
      three subgroups, depending on the duration of their disease: < 1 year: "Short", 1
      - 10 years: "Middle", > 10 years: "Long". For comparison with the metal detector
      test scintigraphic studies of esophageal and gastric transit were performed in 17
      patients and small intestinal transit was studied by use of the H2-lactulose
      breath test in 20 patients with long-standing DM Type-1. In Type-1 DM there is an
      increase of gastric (135 +/- 18, p < 0.01; 218 +/- 26, p < 0.0001 vs. 73 +/- 7
      min.) and large intestinal transit times (79 +/- 18, P < 0.02; 76 +/- 11, p <
      0.04 vs. 40 +/- 5 h) in patients with middle or long standing DM. In Type-2 DM
      similar transit disturbances occur (gastric emptying, long group: 120 +/- 15
      min., p < 0.02; colonic transit, long group: 80 +/- 13 h, p < 0.01). In uremia
      transit disturbances were only found in patients with chronic ambulatory
      peritoneal dialysis (colonic transit: 71 +/- 9 h, p < 0.05). In 65% gastric
      scintigraphy and in 55% of cases the H2-lactulose breath test showed a
      prolongation of gastric emptying or a prolonged mouth-to-cecum transit. Transit
      disorders can occur in every stage of DM with preferential involvement of the
      stomach and the colon. These findings are of clinical relevance, since transit
      disturbances can result in instable metabolic condition.

PMID- 8525656
TI  - Relation between autoimmune liver diseases and viral hepatitis: clinical and
      serological characteristics in 859 patients.
AB  - An etiopathological link between hepatitis virus infection and autoimmune liver
      disease, in particular autoimmune hepatitis has been suggested. In some patients
      features of both viral and autoimmune disease are present. We have studied 352
      patients with autoimmune liver disease and 507 patients with viral hepatitis for
      diagnostic characteristics as well as for evidence of an etiological connection.
      38 of the 201 patients with hepatitis C (19%) and 42 of the 306 patients with
      hepatitis B (14%) had significant titres of autoantibodies (ANA, SMA or LKM). SLA
      autoantibodies were found exclusively in patients with autoimmune liver disease.
      LKM auto-antibody was found in only one of the 201 HCV patients. Evidence of past
      or present hepatitis B virus and past hepatitis A virus infection was most common
      in the hepatitis C virus patients and least common in autoimmune hepatitis. 28 of
      the 352 patients with autoimmune liver diseases tested positive in the second
      generation anti-HCV ELISA, but only five patients (two with autoimmune hepatitis,
      one with primary sclerosing cholangitis and two with primary biliary cirrhosis)
      were positive in confirmatory anti-HCV assays, and only in these could HCV-RNA be
      isolated. Autoimmune hepatitis patients had significantly higher transaminase,
      GLDH and IgG levels. HLA-B8, HLA-DR3 and HLA-DR4 were significantly more common
      in autoimmune hepatitis. Distinction between autoimmune liver disease and viral
      hepatitis C could be made reliably on clinical and laboratory grounds. Our data
      show that a link between hepatitis A, B, or C virus infection and autoimmune
      liver diseases is highly unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525657
TI  - Intestinal pseudoobstruction as a feature of myotonic muscular dystrophy.
AB  - We report two cases of intestinal pseudoobstruction caused by visceral smooth
      muscle involvement due to myotonic muscular dystrophy. Two patients with myotonic
      muscular dystrophy presented with abdominal pain, distention, constipation, and
      vomiting. The exclusion of mechanical obstruction by plain abdominal radiography,
      contrast studies, and colonoscopy led to the diagnosis of intestinal
      pseudoobstruction. Diagnosis was confirmed by manometric and cineradiographic
      findings of abnormal intestinal motility. Conservative management including
      laxatives and cisapride led to the resolution of the pseudoobstruction syndrome
      and long-term remission without relapses during a two year follow-up. In patients
      with known myotonic dystrophy the occurrence of intestinal pseudoobstruction
      should be considered in order to avoid unnecessary laparotomies.

PMID- 8525658
TI  - Adenoma of the papilla of Vater: a possible role for intraductal ultrasound
      (IDUS).
AB  - Like in adenomas of the colon, an adenoma-carcinoma sequence is expected from
      adenomatous growths in the papilla of Vater. Papilloadenomas must therefore be
      resected. Imaging techniques have a decisive influence on the choice of operative
      technique and consequently on perioperative mortality. Using conventional
      endoscopic ultrasonography, detection of lesions smaller than 10 mm in diameter
      is rare. The probes available up to now for intraductal sonography with an
      external diameter of between 3.4 and 12 mm were too rigid and could be inserted
      transpapillarily in only a few cases. The recent development, however, of high
      frequency, extremely flexible ultrasound catheters with an external diameter of
      1.17 mm makes intraductal examination of the pancreatic ductal system possible.
      We present a case of a 66 year-old female patient, in whom, for the first time, a
      histologically adenomatous lesion of the papilla of Vater could be examined with
      intraductal sonography using the endoscopic retrograde, transpapillary approach.
      As there was no evidence of infiltrative growth, the patient underwent a modified
      duodenum-preserving resection of the pancreatic head. Histological examination of
      the resected specimen confirmed the preoperative intraductal sonography findings.
      Since conventional endosonography did not detect the lesion in this case,
      intraductal sonography with flexible, high-frequency catheters as presented here,
      clearly may have a role in extending the possibilities of preoperative
      examination, especially of focal lesions in the periampullary region.

PMID- 8525659
TI  - Hepatic manifestation of hemolytic uremic syndrome in an allogeneic bone marrow
      transplant recipient.
AB  - A 33-year-old woman presented 42 days after allogeneic bone marrow
      transplantation for acute monocytic leukemia (AML, FAB M5) with persistent
      thrombocytopenia, acute renal failure and Coombs negative hemolytic anemia. In
      the absence of the disseminated intravascular coagulation the diagnosis of
      hemolytic uremic syndrome due to immunosuppression with cyclosporin A was
      supposed. Because cessation of cyclosporin A and therapeutic infusions of fresh
      frozen plasma had failed, plasmaseparation therapy was started on day 79 after
      bone marrow transplantation. While hemolytic anemia improved during ongoing
      plasmaseparations the patient developed cholestatic liver failure due to hepatic
      manifestation of HUS. The histological lesions of liver involvement in thrombotic
      microangiopathies are discussed and a review of the literature is presented.

PMID- 8525660
TI  - Alcohol and liver fibrosis--pathobiochemistry and treatment.
AB  - In Western societies roughly 50% of all cases of liver cirrhosis are related to
      alcohol abuse. The oxidative metabolite of ethanol, acetaldehyde, often in
      conjunction with viral or metabolic liver disease, is implicated as the major
      cause for liver fibrogenesis. Acetaldehyde damages cell membranes, initiates
      lipid peroxidation and forms noxious protein adducts, resulting in the activation
      of Kupffer cells and perisinusoidal lipocytes/portal fibroblasts. The activation
      of lipocytes and fibroblasts to a proliferative and collagen-producing
      myofibroblast-like phenotype is triggered by the release of fibrogenic factors
      such as platelet-derived growth factor (PDGF) and transforming growth factor-beta
      (TGF-beta) from the activated Kupffer cells. Due to the socioeconomic burden
      inflicted by cirrhosis, antifibrotic treatment is urgently needed. Strategies to
      prevent or reverse cirrhosis must interrupt the continuous process of
      pathological wound healing in the liver. An antifibrotic effect has been
      demonstrated for the interferons, prostaglandins E and relaxin. Polyunsaturated
      lecithin, silymarin and ursodeoxycholic acid, agents with a high hepatotropism
      and a good safety-profile, appear to have antifibrotic properties. Targeted
      approaches include the specific removal of matrix-bound fibrogenic growth factors
      and the induction of stress-relaxation of the activated mesenchymal cells by
      biologically active matrix-peptides and their stable analogues. Since serum tests
      for the non-invasive assessment of collagen synthesis and degradation in the
      liver are now available, rapid progress in the development and clinical
      application of antifibrotic drugs can be anticipated.

PMID- 8525661
TI  - [Amylin: from humans and mice].

PMID- 8525662
TI  - [Is contrast CT in acute pancreatitis harmful?].

PMID- 8525663
TI  - [Somatic gene transfer in hepatic cystic fibrosis?].

PMID- 8525664
TI  - Are scintigraphic esophageal transit studies necessary to detect the potential
      for esophageal injury of new drugs?

PMID- 8525665
TI  - Gastrointestinal transport and barrier function in health and disease. Berlin, 16
      17 September 1995. Abstracts.

PMID- 8525666
TI  - Guidelines for the prevention of colorectal cancer: update based on new data.
      World Health Organization Collaborating Center for the Prevention of Colorectal
      Cancer.

PMID- 8525667
TI  - [New aspects of blood coagulation inhibitory therapy within the scope of
      percutaneous transluminal coronary angioplasty (PTCA)].
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is increasingly extended to
      patients with complex stenosis morphology or acute coronary insufficiency
      syndromes. Especially these patients are at high risk to suffer thrombotic
      complications during PTCA. Thus an effective anticoagulant regimen is of great
      importance during PTCA. PTCA-induced damage of the arterial wall induces the
      formation of a platelet-rich thrombus. After adhesion of platelets to the
      arterial wall further platelet aggregation is stimulated mainly by activated
      thrombin, followed by fibrin formation stabilizing the growing thrombus. This
      article describes the pathophysiologic basis of coagulation and thrombus
      formation during PTCA and potential targets for a therapeutic intervention. The
      results of clinical studies regarding the currently available antithrombotic,
      antiplatelet, and thrombolytic therapies are described. Furthermore, the results
      are reported of clinical studies of newer anticoagulant strategies such as
      inhibition of the platelet glycoprotein receptor GP IIb/IIIa with monoclonal
      antibodies and direct inhibition of activated thrombin with hirudin analogues. At
      present an aggressive anticoagulant regimen with heparin is recommended during
      the PTCA procedure. Heparin should not be continued after the intervention unless
      a complication during the procedure has occurred. Already before PTCA patients
      should receive 100 mg aspirin daily. Thrombolytic therapy during PTCA has failed
      to demonstrate an improvement of clinical results. Thus its use should be limited
      to bail-out situations. First results with hirudin analogues and GP IIb/IIIa
      receptor antagonists are promising. Further studies are, however, warranted
      before a general use can be recommended.

PMID- 8525668
TI  - [Cardiovascular parameters in transient hypothyroidism].
AB  - Cardiovascular manifestations are a frequent finding in hypothyroidism. Thus,
      blood-pressure measurements, longtime electrographic monitoring, and
      spiroergometry were examined in 20 patients with transitory hypothyroidism. In
      the patients with thyroid carcinoma, total thyroidectomy was performed.
      Measurements were made in hypothyroidism and after TSH-suppression with L
      thyroxine. Thirty-five patients in whom intracardiac catheter examination ruled
      out cardiopulmonary disease served as controls. Cardiopulmonary exercise was done
      by bicycle exercise testing. In transitory hypothyroidism an increase of
      diastolic blood pressure was found at rest (p = 0.02) and during exercise (p =
      0.002), which was reversible after T4-therapy. Compared to the controls diastolic
      blood pressure in hypothyroidism was increased at rest (p = 0.014) and during
      exercise (p = 0.005). ECG-monitoring showed a day-night difference in heart rate
      in hypothyroid patients and after therapy. The mean heart rate (74 vs. 88 beats
      per minute; p = 0.0006), the minimal (p = 0.0062) and the maximal heart rate (p =
      0.0016) during the day were decreased in hypothyroidism compared to euthyroidism.
      There were no atrioventricular blocks in transitory hypothyroidism and no
      increase of ventricular or supraventricular premature beats after high-dose T4
      treatment. Spiroergometry showed no change in ventilation and an increased growth
      in heart rate (p = 0.021) associated with good working capacity in hypothyroid
      patients. Heart rate at rest (p = 0.004) and at the anaerobic threshold (p =
      0.03) were decreased in transitory hypothyroidism.

PMID- 8525669
TI  - [Comparison of invasive blood pressure measurement in the aorta with indirect
      oscillometric blood pressure measurement at the wrist and forearm].
AB  - Indirectly measured blood pressure at the wrist or upper arm was compared with
      directly measured values in the aortic arch during routinely performed diagnostic
      cardiac catheterization in 100 patients (31-80 years, mean 59.3 years, 60%
      males). The noninvasive measurements were carried out by oscillometric devices,
      NAiS Blood Pressure Watch for measurements at the wrist, and Hestia OZ80 at the
      upper arm. Systolic blood pressure measured at the wrist was 4.3 +/- 14.1 mm Hg,
      and the diastolic value 6.0 +/- 8.9 mm Hg higher than when measured at the aortic
      arch; the difference was significant in both cases. Correlation coefficients were
      0.85 for systolic and 0.71 for diastolic blood pressure. In 16% of the patients
      the systolic blood pressure at the wrist differed more than +/- 20 mm Hg. The
      diastolic blood pressure at the wrist measured more than +/- 20 mm Hg higher than
      in the aorta in 5% of the patients. At the upper arm mean systolic values were
      not different to the aorta. The diastolic pressure was 9.3 +/- 9.8 mm Hg higher
      in the aorta than at the upper arm. To verify the accuracy of values measured
      with the NAiS Blood Pressure Watch compared with the standard technique at the
      upper arm, sequential measurements were made at wrist and ipsilateral upper arm
      in the same group of 100 patients. The systolic blood pressure at the left wrist
      was 3.4 +/- 13.3 mm Hg higher and the diastolic pressure 3.8 +/- 9.5 mm Hg lower
      than at the upper arm. Only 53% of systolic values lay within a range of +/- 10
      mm Hg. The correspondence between wrist and upper arm values was better for
      diastolic blood pressure, the values differing by less than +/- 10 mm Hg in two
      thirds of patients. Self-measurement of arterial blood pressure with an
      oscillometric device at the wrist can be recommended only in individual cases
      with a difference of simultaneously measured values at the upper arm of less than
      +/- 10 mm Hg for systolic and diastolic blood pressures. The standard method for
      indirectly measuring arterial blood pressure remains the measurement at the upper
      arm site, which nevertheless showed a systolic pseudohypertension (deviation of
      more than 10 mm Hg) in comparison to the invasively measured values in 15% of our
      selected patients and a diastolic pseudohypertension (deviation of more than 15
      mm Hg) in 23% of the patients.

PMID- 8525670
TI  - [Differentiated evaluation of heart valve stenosis by expanded Bernoulli equation
      -in vitro studies of model stenoses].
AB  - A suitable measure for the hydrodynamic assessment of heart valve stenoses must
      be independent of flow and should correspond to the morphology of the stenoses.
      The "effective orifice area" according to Gorlin does not fulfil this
      requirement, generally, because it is constant only under special conditions.
      This suggests the development of a multidimensional stenosis model. The idea for
      doing so is based on hydrodynamic evaluation of different elementary stenosis
      types in comparison with a valve that behaves like Gorlin's theory. The Bernoulli
      equation can than be expanded definitely and one gets a set of unknown stenosis
      parameters corresponding to the elementary stenoses. The clinical relevance of
      these must be evaluated by morphological evidence and by similarity of the flow
      pressure drop characteristics as compared to real heart valve stenoses. A
      suitable reference valve is the Bjork-Shiley valve. This valve was combined with
      evident elastic and stiff obstacles to opening with the result of flow-pressure
      drop characteristics similar to biological valves written in terms of flow q:
      [formula: see text] where q and q2 are mean flow and mean square flow through the
      valve, respectively. Empirical results reported in the literature can be
      explained as special cases of the stenosis model as demonstrated by examples. The
      proposed equation can be interpreted in physically founded terms in contrast with
      an empirical one. It gives rise to a differentiated evaluation of heart valve
      stenosis by orifice area (c2), elastic properties of shape and material (c1) and
      pre-stress (c0) independent on flow. The model can be extended step by step as
      required.

PMID- 8525671
TI  - [The German Cardiovascular Prevention Study: social gradient for the net effects
      in prevention of hypercholesterolemia].
AB  - Hypercholesterolemia is considered an important risk factor for cardiovascular
      disease. The net effects of 7 years of a community prevention programme using
      principally a high-risk strategy (screening, referrals to general practitioner)
      in the German Cardiovascular Prevention Study (GCP) are analysed according to
      socioeconomic status (SES). Cholesterol was measured in three subsequent cross
      sectional population samples of adults (ages 25-69 years) in 1984-1985, 1988 and
      1991-1992 in the regions of Berlin, Bremen, Stuttgart, Karlsruhe with
      Bruchsal/Mosbach, and Traunstein (n = 11,548, 8743, 8636), in the region of
      Stuttgart only (n = 1791, 1437, 1313) and in the entire West German population (n
      = 4790, 5335, 5311) as reference. SES was determine by an additive, multiple
      index. Variations of means for phases and regions and resultant net differences
      were calculated. From 1984-1985 to 1991-1992 cholesterol declined from 232.7 to
      231.8 mg/dl in the overall regions, from 232.0 to 230.5 mg/dl in Stuttgart, but
      increased from 233.5 to 236.9 mg/dl in the reference region. In the combined
      regions net differences according to SES were -4.2%***1) for the upper class, 
      1.6%** for the middle class and -0.3% for the lower class. Similar results were
      found comparing Stuttgart with the reference region (-5.4%***, -1.4%, -0.1%). The
      GCP intervention for hypercholesterolemia was successful basically only for the
      upper class, if net differences for the means are calculated. Prevention of
      hypercholesterolemia increased the social gradient in the pooled intervention
      regions and in Stuttgart.

PMID- 8525672
TI  - [An interventional study against cigarette smoking among Dusseldorf high school
      students 1992-94].
AB  - Between 1992 and 1994, an interventional program was held in the secondary
      schools ("Hauptschulen") in Dusseldorf contra cigarette smoking. The program was
      conducted in the following way. Half of the schools (intervention schools) were
      involved in this program which consisted of 15 sessions. The other schools served
      as control groups. During the first year of this program school-teachers and a
      physician taught students about the function and the abilities of the healthy
      heart and lung. The students developed adversions to smoking. In addition, the
      students learned by role-plays how to say no to a cigarette without
      embarrassment. These role-plays were videotaped. During the second year of this
      program the role-plays were repeated and teaching about the heart and the lungs
      was augmented. Also, every student got the opportunity to meet and talk with a
      famous athlete. Furthermore, smoking-cessation programs were hold in four
      intervention schools. The program started in the sixth grade with a questionnaire
      administered to 878 schoolchildren. During this time the average age of the
      children was 13 years. Because of a large fluctuation, the questioning could be
      repeated with only 630 of these children (71.8%) after 2 years. At the end of the
      study the number of smokers had increased two times greater in the control
      schools than in the intervention schools (boys: 20.5% points vs 9.4% points;
      girls: 44.3% points vs 21.0% points). Obviously, the continuation of the program
      during the second year was important in making the program successful. Among the
      participants of the intervention program there was a trend to stop smoking. But
      the program was not able to prevent non-smokers from starting the habit. On the
      other hand, of the children who started smoking during the program, more girls in
      the intervention schools quit smoking than in the control schools. At the end of
      the program more girls than boys (mean age 15 years) smoked. Almost one-fourth of
      the boys, and from the control schools one-third of the girls were already daily
      smokers. The smokers obtained cigarettes from kiosks, from friends, vending
      machines, vendors or shops, but seldom from their homes.

PMID- 8525673
TI  - [Prognostic significance of changes in left ventricular diastolic function in
      follow-up of dilatative cardiomyopathy].
AB  - A total of 39 patients with idiopathic dilated cardiomyopathy (IDC) and sinus
      rhythm were examined for correlations between clinical course, systolic/diastolic
      cardiac function, and clinical status according to NYHA class (I-IV). Patients
      were divided in two groups: group 1 included survivors (n = 28, 49 +/- 11 years)
      and group 2 the nonsurvivors (n = 7) and transplanted patients (n = 4
      transplanted; 48 +/- 10 years). Both groups were examined several times, and data
      at baseline were compared with those of the last examination. The follow-up
      period was about 3 years (group 1: 41 +/- 22 months, group 2: 24 +/- 13).
      Baseline conditions were defined at the time when the diagnosis of IDC was
      established. Diastolic cardiac function was evaluated by Doppler echocardiography
      parameters of early (VE) and late diastolic peak velocity (VA), the ratio of
      VE/VA and early deceleration time (EDT). Data for clinical symptoms (NYHA group
      1: 2.5 +/- 0.9 vs. group 2: 2.7 +/- 1.3, NS) systolic [fractional shortening (FS)
      group 1: 0.17 +/- 0.06 vs. group 2: 0.16 +/- 0.06, NS], and diastolic function
      (VE, VA, VE/VA) showed no differences between the two groups. Only the EDT was
      significantly shorter in group 2 (group 1: 196 +/- 64 ms vs. group 2: 119 +/- 43
      ms, P < 0.001) when diagnosis was established. During the follow-up period there
      was an improvement in both groups concerning NYNA class (group 1 from 2.5 +/- 0.9
      to 1.9 +/- 0.7, P < 0.005; group 2 from 2.7 +/- 1.3 to 2.1 +/- 0.9, NS). There
      was a nonsignificant deterioration in systolic function in group 2 (FS, from 0.16
      +/- 0.06 to 0.15 +/- 0.06, P = 0.07), which contrasted to an improvement in group
      1 (from 0.17 +/- 0.06 to 0.20 +/- 0.08, P = 0.06). VE/VA increased in group 2
      (from 1.24 to 1.67 +/- 1.21, P = 0.09) essentially due to a significantly
      increased VE (from 0.66 +/- 0.2 m/s to 0.85 +/- 0.27 m/s, P < 0.05). EDT remained
      shorter in group 2 (group 1.198 +/- 55 ms vs. 149 +/- 84 ms, P < 0.05). In
      conclusion, values of VE > 0.8 m/s, VE/VA > 1.6, and EDT < 150 ms during follow
      up were predictors of poor prognosis in patients with IDC. Patients with a long
      EDT (> 150 ms) had a favorable prognosis for survival.

PMID- 8525674
TI  - [Three AV-nodal pathways in a patient with atypical AV-nodal reentry
      tachycardia].
AB  - In a female patient with paroxysmal AV nodal reentrant tachycardias the
      electrophysiological study revealed three AV nodal pathways. During atrial
      extrastimulation a sudden AH interval prolongation of more than 50 ms ("break"
      phenomenon) was observed twice at one basic cycle length. During ventricular
      extrastimulation a sudden prolongation of the AH interval of the anterograde AV
      nodal conduction of the induced echo beats was recorded. Three AV nodal pathways
      were thus present. The atypical form of AV nodal reentrant tachycardia was
      induced, showing a varying cycle length (290-340 ms). After radiofrequency
      catheter ablation of the fast conducting beta-pathway, another tachycardia was
      initiated, now showing a constant cycle length, using the two remaining, more
      slowly conducting alpha-pathways. One of these was eliminated in another ablation
      procedure.

PMID- 8525675
TI  - [The aortic arch as source of thromboembolism events--significance of
      echocardiography diagnosis].
AB  - A 43-year-old woman presented with acute embolic occlusion of the left brachial
      artery. She was immediately treated by surgical embolectomy. After exclusion of
      other possible embolic sources, the transthoracic and transesophageal
      echocardiographic examination revealed a floating thrombus in the aortic arch.
      There-upon an aortotomy and thrombectomy was performed and showed a normal wall
      structure of the thoracic aorta except for a minimal ulcerated lesion of the
      intima at the aortic arch. This case confirms that transthoracic and
      transesophageal echocardiography are the diagnostic methods of choice for
      detecting thromboembolic sources originating in the heart or thoracic aorta.

PMID- 8525676
TI  - [On the 120th anniversary of the birth of A. A. Ukhtomskii].

PMID- 8525677
TI  - [The self-organization of the brain as the integration of the processes of
      different spatial and time scales].
AB  - The article is devoted to analysis of theoretical aspects of brain functioning.
      The base of authors philosophy is some general principles, which one can see on
      macro- and microlevels of brain functioning organization.

PMID- 8525678
TI  - [The information principle in physiology: an analysis from the position of the
      general theory of functional systems].
AB  - Information principle of the organism functional systems creation is formulated
      in the article. Transformation of organism biological needs on various levels
      into dominant motivation, behaviour and processes of basis needs satisfaction
      without loss in information sense is shown. Information role of emotions is
      analysed. On the base of experimental data is formulated concept of information
      environment of organism. Specially analysed the information basis of human
      psychological activity.

PMID- 8525679
TI  - [The systems organization of the breeding behavior of the moose in its natural
      habitat].
AB  - The complex organisation of moose sexual interrelations in natural environment is
      analysed from the systems point of view. To achieve the useful result--the well
      timed fertilization of the all matured females on the given territory by the most
      strongest males--every year in autumn the multiorganismic system of interaction
      is formed, including the correspondent behavioural activities of local receptive
      females and males of different strength and different age. This system includes
      the sub-system of "rang establishment" between the males (detecting the strongest
      males), which works mainly at the beginning of rut, and the sub-system of mating.
      The features of species-specific behaviour are described, which assist to animals
      mutual detection in the forest, as well as their specific communication during
      the rut. The special attention is devoted to the role of olfactory and acoustic
      signals. The details of the forming, existing and disintegration of stable
      breeding couples are discussed and the breeding ritual itself is described, which
      ensures the achievement of the synchronisation of high sexual excitation in male
      and female. By means of long distance bioradiotelemetry the dynamics of heart and
      breathing rate were investigated as the indicators of animals emotional states on
      the different stages of their sexual behaviour.

PMID- 8525680
TI  - [The network mechanisms of physiological regulation].
AB  - A review of connectionist or network approach to describe and understand
      regulatory processes in organism is presented. Network models of neural, genetic,
      immune and endocrine regulation are considered and a conception of organism as an
      integrative network system is introduced. A new approach to the problem of
      organism state control, called associative control, is proposed and its possible
      medical applications, in particular, in psychotherapy, psychoanalysis and
      alternative medicines are discussed.

PMID- 8525681
TI  - [The biomedical effects of ultraviolet radiation and their mechanisms].
AB  - Human and animal health effects of UVR are considered. At the cellular level UVR
      have been observed to cause changes in the cell division and/or differentiation,
      the loss of specialized functions, mutations, transformation and death. Most of
      these effects occur via mechanism that involves DNA damage and induction of
      pyrimidine dimers. The critical organs for UVR are skin, eye and immune system.
      In the skin UVR can induce erythema, tanning, vitamin D biosynthesis, keratosis,
      elastosis, pigment dystrophy and cancer. UVR has immunosuppressive effect,
      transferable with lymphoid cells, that is critical to the outgrowth of highly
      antigenic UV-induced tumors. UVR also suppress both contact hypersensitivity and
      delayed hypersensitivity responses to a variety of antigens. UVR exposure to the
      eye can induce photokeratoconjunctivitis and plays a significant, role in the
      etiology of cataracts, corneal and retinal degeneration, pterygium and uveal
      melanoma. Information about action spectra, biologically effective doses and
      mechanisms of effects mentioned is presented. Acceptable doses of UVR with regard
      to damage to skin and eye, recommended in some foreign countries are discusses.

PMID- 8525682
TI  - Immunity to St. Louis encephalitis virus by sequential immunization with
      recombinant vaccinia and baculovirus derived PrM/E proteins.
AB  - St. Louis encephalitis (SLE) is an important mosquito-borne disease of great
      public health concern in parts of the United States. South America and Canada.
      Protective immunogens of flaviviruses produced in different expression systems
      have been shown to be effective against virulent virus infection in laboratory
      animal models. Here we show that the pre-membrane and envelope (PrM/E) of SLE
      virus expressed in insect and mammalian cell systems using baculovirus and
      vaccinia virus, respectively, are processed correctly and showed similar
      antigenic characteristics as the authentic proteins. Immunization with the
      recombinant proteins individually or in combination resulted in neutralizing and
      protective immune responses. A schedule consisting of initial immunization with
      recombinant vaccinia virus followed by a secondary boost with recombinant
      baculovirus protein resulted in higher levels of neutralizing and protective
      immune responses. The advantages of the use of such a combined approach as a
      general immunization strategy are discussed.

PMID- 8525683
TI  - Human immune responses to influenza virus vaccines administered by systemic or
      mucosal routes.
AB  - Healthy adult volunteers were immunized by parenteral or oral routes with
      trivalent inactivated influenza vaccine (A/Chile/1/83 (H1N1), A/Mississippi/1/85
      (H3N2), and B/Ann Arbor/1/86), or intranasally with live attenuated, cold-adapted
      influenza type A/Texas/1/85 (H1N1) reassortant virus. In all volunteers, cells
      spontaneously secreting IgA, IgG or IgM antibodies specific to influenza virus
      were detected in peripheral blood on days 6-13 after immunization, and specific
      IgA, IgG and IgM antibodies to influenza vaccine were measured in sera and
      external secretions (saliva and nasal lavage). Following systemic immunization, a
      raise in specific antibodies of all isotypes was observed in sera beginning on
      day 13. Although small variations in IgA and IgM antibodies in saliva and nasal
      lavages were detected, antigen-specific IgG significantly increased between days
      13 and 27. Intranasal administration of attenuated virus induced IgA and IgG
      antibodies in serum as well as in secretions. Serum antibodies were not
      substantially influenced by oral immunization, only a small increase in all
      isotypes was observed in volunteers' sera 21 days after ingestion of vaccine.
      However, in secretions, antigen-specific IgA and IgG responses were detected one
      week after immunization and reached a peak response on day 20. These studies show
      that different routes of immunization can be effective for the induction of
      specific antibodies, and support the concept of the common mucosal immune system
      in humans by demonstrating that the oral or intranasal administration of antigen
      induced specific antibodies of IgA isotype in external secretions, preceded by
      the transient appearance in peripheral blood of specific antibody-producing
      cells.

PMID- 8525684
TI  - Immune responses induced by administration of encapsidated poliovirus replicons
      which express HIV-1 gag and envelope proteins.
AB  - Several viruses have been exploited for the development of recombinant vaccine
      vectors in which to express foreign proteins. Recently, we have described a
      system utilizing the RNA virus, poliovirus. We have constructed poliovirus
      genomes in which regions of the capsid have been substituted with gene fragments
      of the HIV gag and env genes. A complementation system has been designed to
      encapsidate defective genomes by providing the capsid protein in trans from a
      recombinant vaccinia virus (VV-P1). Serial passage in the presence of VV-P1
      resulted in the generation of stocks of these encapsidated replicons. Infection
      of cells with these encapsidated replicons resulted in the expression of the
      recombinant protein as a fusion protein with the poliovirus capsid proteins VP4
      and VP1. In this study, we have utilized encapsidated replicons which express the
      HIV-1-gag capsid protein (p24) as well as 1.5 kb of the HIV-1 env gene. Stocks of
      these encapsidated replicons were obtained by 20 serial passages in the presence
      of VV-P1. In addition, passage of the encapsidated replicons in the presence of
      poliovirus type 2 Lansing resulted in the encapsidation of the replicons by the
      capsid proteins provided by poliovirus. The administration of the type 2
      Lansing/encapsidated replicons expressing HIV-1 gag in BALB/c mice by
      intramuscular, intrarectal, or intragastric routes resulted in the generation of
      antibodies in the serum and secretions against both poliovirus and HIV-1 gag. To
      prove that the replicons alone are immunogenic, we administered replicons
      expressing either HIV-1 gag or env to transgenic mice which expressed the
      receptor for poliovirus type 1. Immunization of these mice by the intramuscular
      route resulted in the generation of serum antibodies specific for poliovirus as
      well as for HIV-1 antigens. The results obtained led us to the conclusion that
      the replicons are immunogenic when given alone or in the presence of poliovirus.
      These results are important for the use of the poliovirus replicons as a
      recombinant vaccine vector.

PMID- 8525685
TI  - Protective efficacy of a parenterally administered MOMP-derived synthetic
      oligopeptide vaccine in a murine model of Chlamydia trachomatis genital tract
      infection: serum neutralizing IgG antibodies do not protect against chlamydial
      genital tract infection.
AB  - The protective efficacy of an alum-adsorbed, parenterally administered synthetic
      oligopeptide immunogen corresponding to antigenically common T-helper and
      neutralizing B-cell epitopes of the Chlamydia trachomatis major outer membrane
      protein was studied in a murine model of chlamydial genital tract infection. Mice
      produced high levels of anti-chlamydial serum IgG neutralizing antibodies
      following subcutaneous immunization with the alum-adsorbed oligopeptide. Lower
      but detectable levels of chlamydial specific IgG antibodies were found in vaginal
      washes. IgG1 was the predominant isotype present in sera and vaginal washes.
      Chlamydial-specific IgA was not present in either the sera or vaginal washes of
      immunized mice. Vaccinated and control mice were challenged intravaginally or
      intrauterinally with low, medium, or high doses of C. trachomatis serovar D
      challenge inocula. Protection was assessed by performing quantitative chlamydial
      cervico-vaginal cultures over the course of the infection period. There were no
      statistically significant differences between groups of immunized and control
      mice in either colonization, shedding, or duration of infection. These findings
      demonstrate that parenteral immunization with the oligopeptide (serum
      neutralizing antibodies) is ineffective in preventing chlamydial genital tract
      infection. It is possible, since chlamydial infection is restricted to the
      genital tract mucosae, that a more accurate evaluation of the oligopeptide
      vaccine potential will require local rather than systemic immunization.

PMID- 8525686
TI  - Full protection in mink against mink enteritis virus with new generation canine
      parvovirus vaccines based on synthetic peptide or recombinant protein.
AB  - Two recently developed vaccine--one based on synthetic peptide and one based on
      recombinant capsid protein--fully protected dogs against heavy experimental
      canine parvovirus (CPV) infection. The high sequence homology ( > 98%) and
      antigenic similarity between CPV and mink enteritis virus (MEV), feline
      panleukopenia virus, and raccoon parvovirus, suggest that both vaccines could
      protect mink, cats and raccoons against these respective host range variants.
      This was tested in mink and turned out to be the case. The two vaccines were
      fully protective and as effective as a conventional commercial vaccine based on
      inactivated virus. Surprisingly, this protection was obtained after only a single
      injection. Furthermore, the vaccinal dose of 150 micrograms of conjugated peptide
      or 3 micrograms of recombinant VP2 particles per animal, are sufficiently low to
      be cost-effective and applicable on a large scale.

PMID- 8525687
TI  - Report of a meeting on "Vaccines; new technologies and applications".

PMID- 8525688
TI  - Reappraisal of existing methods for potency testing of vaccines against tetanus
      and diphtheria.

PMID- 8525689
TI  - Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella
      vaccine (Varivax) in healthy adolescents and adults. Oka/Merck Varicella Vaccine
      Study Group.
AB  - A multicenter clinical trial was conducted among 757 healthy adolescents and
      adults, 13-54 years, to compare two regimens of Oka/Merck varicella vaccine with
      respect to safety, tolerability, and immunogenicity. Participants were randomized
      to receive two injections of vaccine either four or eight weeks apart and were
      followed for clinical reactions and serologic response. The two vaccine regimens
      were equally well tolerated. The seroconversion rates (gpELISA) four weeks after
      injection 1 and 2 were 72 and 99%, respectively, for those who received vaccine
      four weeks apart and 78 and 99%, respectively, for those who received vaccine
      eight weeks apart. The differences in seroconversion rates were not statistically
      significant. However, delaying the second dose to eight weeks resulted in a
      higher antibody titer one month after the second injection. Administration of a
      two-dose regimen of varicella vaccine to susceptible adolescents and adults is
      well tolerated and highly immunogenic.

PMID- 8525690
TI  - Newborn universal immunisation against hepatitis B: immunogenicity and
      reactogenicity of simultaneous administration of diphtheria/tetanus/pertussis
      (DTP) and oral polio vaccines with hepatitis B vaccine at 0, 2 and 6 months of
      age.
AB  - The reactogenicity and immunogenicity of the administration of recombinant
      vaccine against hepatitis B simultaneously (but at separate sites) with
      diphtheria/tetanus/pertussis (DTP) and oral polio vaccines were examined. Six
      hundred and twenty-six children (group I) were given hepatitis B vaccine at 0, 2
      and 6 months of age; the other vaccines were administered at 2, 4 and 6 months of
      age. A control group of 731 children (group II) received only DTP and oral polio
      vaccines. The results showed that 93% of the infants in group I had anti-HBs
      titres above the protective level ( > or = 10 mIU ml-1) after vaccination. There
      were no differences in the immune responses for DTP and polio between the two
      study groups. The vaccine efficacy against poliomyelitis was 96% for serotype I,
      100% for serotype II and 97-98% for serotype III. Of the infants in both groups,
      97% had antibodies against B. pertussis; all children were positive for tetanus
      and diphtheria. There were no differences in the incidences of general reactions
      between groups. Local swelling and redness were reported following 4.2 and 4.4%,
      respectively, of all injections of hepatitis B vaccine. These reactions were
      reported following 31 and 33%, respectively, of all doses of DTP vaccine. It can
      be concluded that the simultaneous administration of hepatitis B vaccine with the
      DTP and polio vaccines is well-tolerated; hepatitis B vaccine remained highly
      immunogenic and did not interfere with the immune response to the other antigens.

PMID- 8525691
TI  - Randomized comparison of 5 and 10 microgram doses of two recombinant hepatitis B
      vaccines.
AB  - The high cost of hepatitis B vaccines remains an obstacle to their use. Since the
      recommended adult dose of Recombivax HB (MSD) is 10 micrograms and that of
      Engerix B (SKB) is 20 micrograms, we sought to determine if 10 microgram doses of
      each vaccine are equally immunogenic. Further, since 5 microgram doses of
      Recombivax are routinely used in those < or = 29 years of age in the US military,
      we sought to compare this dose with 5 microgram doses of Engerix B. Lower doses
      of Engerix would result in vaccine cost savings. METHODS: members of the Belize
      Defence Force who were > or = 18 years of age (median 24) without detectable anti
      HBc were randomly assigned to receive Recombivax, 5 or 10 micrograms, or ENgerix,
      5 or 10 micrograms IM at 0, 1, and 6 months. Randomization was weighted toward
      Engerix. RESULTS: after 3 doses, geometric mean concentrations (GMC) of anti-HBs
      were highest among those receiving Recombivax 10 micrograms (n=22) or 5
      micrograms (n=46) with GMC anti-HBs of 744 and 570 mIU ml-1, respectively.
      Similar proportions in the two groups developed > or = 10 mIU m-1 anti-HBs (100
      and 98%). Among the 91 people who received Engerix 10 micrograms, the GMC anti
      HBs was 325 mIU ml-1 and 91% developed > or = 10 mIU ml-1. The 87 people who
      received Engerix 5 micrograms had the lowest GMC, 177 mIU ml-1 (p < 0.05 compared
      with either Recombivax group). Only 86% attained > or = 10 mIU ml-1 anti-HBs (p >
      0.05 compared with other regimens). The proportion attaining > or = 100 mIU ml-1
      was lower in the 5 microgram Engerix group (63%) compared with 80% in the 5
      microgram or 95% in the 10 microgram Recombivax groups (p < 0.05). CONCLUSIONS:
      Engerix administered in 5 microgram doses is less immunogenic than 5 or 10
      microgram doses of Recombivax. In healthy populations < 30 years of age, regimens
      of half the recommended adult dose (5 micrograms of Recombivax or 10 micrograms
      of Engerix) are highly immunogenic and may result in significant vaccine cost
      savings.

PMID- 8525692
TI  - Heat stabilized, infectious poliovirus.
AB  - Polioviruses type 1 (Mahoney) and type 3 (Sabin) were treated with the antiviral
      pyridazinamine R78206 by first binding the compound to the virus and then
      removing unbound compound by dialysis. As a result of this treatment, both
      poliovirus strains were protected against thermal inactivation at 46 degrees C.
      The R78206 treatment did not cause inactivation except with the Sabin 3 strain at
      high R78206 concentrations.

PMID- 8525693
TI  - The effects of vaccination with inactivated uropathogenic bacteria in recurrent
      urinary tract infections of children.
AB  - Secretory IgA (sIgA) is an important parameter in the predisposition to recurrent
      urinary tract infection (UTI). We investigated whether sIgA and frequency of UTI
      could be positively influenced by intramuscular vaccination with inactivated
      uropathogenic bacteria (Solco-Urovac). Ten otherwise healthy girls aged from 5 to
      11 years (mean 9  1.7 years) with recurrent UTI were immunized with Solco-Urovac
      by i.m. injections three times at weekly intervals. A booster injection was given
      after 6 months. Urinary sIgA secretory component (SC) concentration was
      determined by radial immunodiffusion assay. Ten other age-matched girls with UTI
      were not immunized. Immunization therapy caused a significant reduction in the
      frequency of infection and an increase in urinary sIgA SC, while in the
      nonvaccinated group the values remained constant.

PMID- 8525694
TI  - Efficient purification and rigorous characterisation of a recombinant gp120 for
      HIV vaccine studies.
AB  - A recombinant HIV-1 gp120 (rgp120) was expressed in a permanent Chinese Hamster
      Ovary (CHO) cell line (L761h) that constitutively secretes the product of clone
      p4 derived from the env gene of HIV-1 isolate GB8. The rgp120 was isolated from
      cell culture supernatants by a simple, rapid, non-denaturing and efficient
      purification procedure based on a novel combination of lectin affinity and FPLC
      ion-exchange chromatography. The purity of the isolated glycoprotein was
      rigorously confirmed by SDS-PAGE, capillary electrophoresis, laser desorption
      mass spectrometry, total amino acid analysis and N-terminal amino acid
      sequencing. The retention of biological activity by the purified rgp120 was
      assessed by determining the dissociation constant of rgp120 binding to sCD4.
      After formulation of this highly purified and biologically active rgp120 with
      "conventional" adjuvants, including types already used in clinical trials of
      candidate gp120-based HIV vaccines, antibody responses in immunised rabbits were
      analysed using panels of overlapping synthetic peptides. The consequences of
      using currently available adjuvants to deliver highly specialised and perhaps
      conformation-dependent molecules, like HIV gp120, are presented and discussed in
      the context of HIV vaccine development.

PMID- 8525695
TI  - [Selenium content of tea from different provinces of the People's Republic of
      China].
AB  - In the People's Republic of China there are wide regions where many people suffer
      from strong selenium deficiency. In order to elucidate the possibilities to
      compensate this state of need by the national drink, the selenium contents of 31
      tea samples from nine provinces of the PR China were determined by hydride
      generation atomic absorption spectrometry (HG-AAS). The Se contents of the ten
      analyzed tea samples from one region with soils containing high selenium amounts
      range from 83 ng/g to 7530 ng/g. These results are in contrast to the Se contents
      of the remaining tea samples from other regions, which range from 28 to 573 ng/g.
      The extractable part of selenium in the tea drink ranges between 7% and 27%
      without significant difference among different tea samples. The accuracy of Se
      determination was tested by using one tea standard reference material. The daily
      consumption of one "Se tea" examined in this study assures that people who suffer
      from a Se deficiency resume enough of it. Drinking normal quantities of this tea
      an intoxication by Se is not to be expected.

PMID- 8525696
TI  - Aluminium and fluoride in hospital daily diets and in teas.
AB  - The levels of aluminium and fluoride have been determined in hospital daily diets
      including breakfast, dinner and supper, as well as in black teas and herbal teas
      purchased from the local market. In tea, aluminium was determined directly in a
      sample solution by atomic absorption spectroscopy using nitrous oxide and an
      acetylene flame. For analysis of the hospital diet, samples containing lower
      levels of aluminium were analysed using a spectrophotometric method which
      measured aluminium in the form of a 8-hydroxyquinoline complex. Decomposition of
      the samples was achieved using a mixture of concentrated acids [nitric (HNO3),
      perchloric (HClO4) and sulphuric (H2SO4)] in platinum dishes. Fluoride was
      assayed by spectrophotometry using a microdiffusion procedure with a mixture of
      concentrated HClO4 and silver sulphate, trace amounts of the released fluoride
      [as hydrogen fluoride (HF)] were trapped on the alkaline surface of a Petri dish
      and then determined in the form of an alizarin-fluoride complex. The mean level
      of aluminium found in hospital daily diets amounted to 21.3 +/- 12.3 mg and the
      mean level of fluoride was 1.38 +/- 1.12 mg per adult person. In the 16 samples
      of commerically available brands of black teas, the levels of aluminium and
      fluoride ranged from 445 to 1552 ppm (mean = 897 +/- 264 ppm) and from 30 to 340
      ppm (mean 141 +/- 85 ppm), respectively. In six herbal teas, the mean levels of
      aluminium and fluoride were lower, and amounted to 218.9 +/- 150.7 ppm and 6.0 +/
      6.9 ppm, respectively. This study has shown that concern about a high intake of
      aluminium and fluoride from these foods is unfounded.

PMID- 8525697
TI  - Levels of some trace elements in edible fungi.
AB  - A number of common edible fungi were analysed for their contents of Pg, Cd, Cr,
      Ni, Co, Zn, Cu, Mn and Se. The results indicate that the Cd level in the species
      Rozites caperata can be as high as several mg/kg fresh weight. In Lycoperdon
      perlatum and Macrolepiota procera the Pb level was found to be up to 2.5 mg/kg.
      The Ni level was at or below 0.1 mg/kg in all species, with the exception of
      Albatrellus ovinus, which had a mean concentration of 0.72 mg/kg. The level of Cr
      was highest in M. procera with a mean of 0.091 mg/kg. In a single sample of the
      species Agaricus augustus, the concentration of Co was found to be exceptionally
      high at 0.28 mg/kg. Zn and Cu levels were highest in L. perlatum and M. procera.
      Mn levels were fairly similar in the different species. The results of several
      surveys show that there can be large differences in the concentrations of the
      same metal (e.g. Pb) in the same species. The Se level was found to be very high
      in the species Boletus edulis, as has been shown by others. In the other species
      analysed the level of Se was low.

PMID- 8525698
TI  - Characterisation of a fungus reference material, and a guide for use.
AB  - A reference material consisting of an edible fungus, Cantharellus tubaeformis,
      with certified levels of Pb, Cd, Zn, Cu, Mn, Cr, Ni, Co and Fe was produced,
      primarily for use in a project concerning metal determination in common edible
      fungi. The C. tubaeformis was dried, homogenised and sieved using non
      contaminating equipment. It was then mixed thoroughly before bottling in
      polythene containers. Homogeneity was checked by multiple analysis of a number of
      containers, and was found to be satisfactory. Each metal was determined by at
      least two different methods of analysis. A total of ten laboratories participated
      in the certification process. All the metals analysed in this certified reference
      material showed good agreement with the levels found in fresh C. tubaeformis,
      when the difference in water content was accounted for. This indicates that no
      contamination of the fungus reference material occurred during the production. It
      is concluded that the 95% confidence interval for the true mean, as defined for
      the different metals, is of limited value from the user's point of view.
      Therefore, a more user-oriented way of presenting the results, based on the
      within- and between-laboratory standard deviations of the certification process,
      is suggested. These are 95/95% tolerance intervals within which the user's
      results should fall. Different intervals are given, one of which indicates the
      largest acceptable difference between duplicates and another for the acceptable
      range of future means.

PMID- 8525699
TI  - Determination of polycyclic aromatic hydrocarbons in water and water-based
      alcoholic beverages.
AB  - This paper proposes a simple HPLC method for the determination of polycyclic
      aromatic hydrocarbons (PAHs) in water, wine and beer. Samples were purified by
      PAH collection in solid-phase extraction (SPE) and analysed by reversed-phase
      HPLC (Supelcosil LC-PAH column from Supelco). For the beer sample, recoveries
      amounted to 28% for naphthalene and varied from 57% to 103% for the other PAHs;
      results are quantitative starting from fluoranthene (FI, the seventh component
      eluted). Almost all the beer and wine samples showed the presence of
      benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF), benzo(a)pyrene (BaP),
      benz(ghi)perylene (BghiP) and indeno(1,2,3-cd)pyrene (IP), and in some cases
      there were traces of FI, benzo(a)anthracene (BaA) and dibenz(ah) anthracene
      (DBahA). Total contents of PAHs ranged from trace amounts to 0.72 ppb. Traces of
      BbF, BkF, BaP, BghiP and IP were also found in the wine samples.

PMID- 8525700
TI  - Solid phase extraction for the confirmation of results in polar pesticides
      residue analysis by HPTLC.
AB  - HPTLC is a convenient method for confirming the presence and identification of
      pesticide residues following gas chromatographic analysis of sample solutions
      obtained by clean-up according to the Deutsche Forschungsgemeinschaft
      multiresidue method S 19. For several crops, however, the polar eluates 4 and 5
      obtained from the small silica gel column are abounding with co-extractives which
      interfere with HPTLC determination and also with GLC in some cases. They are
      effectively removed by solid phase extraction on a small aminopropyl cartridge,
      using a tertbutyl methyl ether/methanol (99 + 1) mixture as the eluant. The
      recoveries for 28 polar pesticides were not adversely affected.

PMID- 8525701
TI  - Prediction of the percentages of cows', goats' and ewes' milk in "Iberico" cheese
      by electrophoretic analysis in whey proteins.
AB  - Stepwise multiple linear regression (SMLR) and principal components regression
      (PCR) have been used to predict the percentages of cows', goats' and ewes' milk
      in ?Iberico? cheese, using the results obtained by electrophoretic analysis (PAGE
      and IEF) of whey proteins, using standard cheeses. Similar predictions of the
      percentages of milks from the three species were obtained when either SMLR or PCR
      were applied to the electrophoretic data, i.e., the optical intensity of the
      electrophoretic bands (PAGE or IEF) of the whey proteins. The root mean square
      error of prediction in cross-validation (RMSEPCV) was lower than 4% in all cases.

PMID- 8525702
TI  - Inactivation kinetics of gamma-glutamyltransferase during the heating of milk.
AB  - The inactivation of gamma-glutamyltransferase (GGT, E.C.2.3.2.2) during the
      heating of milk to between 65.0 degrees C and 76.0 degrees C for periods of 5 s
      to 1000 s follows a first-order reaction (energy of activation 457 kJ/mol) and
      can be used to monitor the process of milk pasteurisation. GGT activity in raw
      milks from individual cows showed only little variation (5.92 +/- 0.59 units).
      Residual GGT activity in 17 commercial milks ranged between 1% and 20%,
      indicating a heat treatment at the upper limit of the permitted pasteurisation
      conditions.

PMID- 8525703
TI  - Alteration of apparent viscosity of irradiated pepper--a tool for semi
      quantitative estimation of irradiation dose.
AB  - The feasibility of using apparent viscosity (eta a) as a method for detecting the
      occurrence of previous irradiation of pepper was studied. Apparent viscosity of
      heat-treated suspensions of white and black pepper, nonirradiated or irradiated
      with different doses of ionising radiation (gamma), was measured under different
      "shear rates". Results of previous research were therefore expanded and their
      usefulness examined; low shear rate conditions were found to be preferable for
      the detection and semi-quantitative evaluation of irradiation doses. The
      experimental methodology for semi-quantitative estimation was developed and its
      scope and limitations are presented.

PMID- 8525704
TI  - [Electron spin resonance spectroscopy investigations of fresh fruit. Evidence of
      treatment with ionizing radiation].
AB  - This paper describes the development of a method for the identification of
      irradiated fresh fruits by measurement of the e.p.r. spectra of pips, kernels or
      stones. Measurement parameters were optimized and the irradiation specific
      spectrum was assigned to a cellulose radical by comparison with the e.p.r.
      spectrum of pure cellulose. Several fruits especially different varieties of
      strawberries were examined giving the following results: Detectable minimum doses
      were between 0.4 kGy and 0.9 kGy and the intensity of the irradiation specific
      signals was found to be linear up to doses of 11 kGy. The lifetime of the
      specific radicals (at room temperature and at deep freezing temperatures) was
      long enough compared to the storage time of fresh fruits. Additional information
      about the nature of the unspecific central signal was gained measuring the
      samples which were stored at different temperatures. The main conclusion of this
      study is that the e.p.r. method seemes to be well suited for the use in routine
      control and should be tested in an intercomparison to establish a routine method
      for the identification of irradiated fresh fruits.

PMID- 8525705
TI  - A chemical study of the protein fractions of Tarragona hazelnuts (Corylus
      avellana).
AB  - The protein contents of six Tarragona hazelnuts varieties were determined. The
      protein contents (g protein per 100 g hazelnuts) were between 12.1 g/100 g and
      18.8 g/100 g, according to variety; a mean discrepancy of 2.3 g/100 g was
      detected between data from the same variety grown with irrigation and using a dry
      farming method. Percentages of albumins, globulins, glutelins and prolamines were
      also determined. In all varieties albumins and globulins were the major
      fractions, averaging about 86.58% of the total protein content.

PMID- 8525706
TI  - Reaction of 3-deoxypentosulose with N-methyl- and N,N-dimethylguanidine as model
      reagents for protein-bound arginine and for creatine.
AB  - Deoxyosones are established key-intermediates in Maillard processes. Due to their
      dicarbonyl structure, they undergo condensation to form heterocyclic compounds
      with guanidine derivatives. In biological systems, guanidino functions are
      present in protein-bound arginine moieties as well as in creatine. The reactivity
      of such structures towards 3-deoxypentosulose is investigated with N-methyl- and
      N,N-dimethylguanidine as model substrates. Two diastereoisomers each are isolated
      from both reactions; they have been characterized unequivocally, respectively, as
      4-(2,3-dihydroxypropyl)-2-N-methylamino-2-imidazoline-5-one and 4-hydroxy-5-(2,3
      dihydroxypropyl)-2-(N,N-dimethylamino)-5H-imidazole. In aqueous medium as well as
      in the crystalline state, both diastereoisomer pairs exist in different
      tautomeric forms.

PMID- 8525707
TI  - Influence of pectin structure on the interaction with bile acids under in vitro
      conditions.
AB  - Structural parameters of pectin (a polysaccharide and important component of
      dietary fibre) influence the interaction with bile acids (BA). The effect of
      experimental conditions (concentration of pectin, BA and Ca2+) on such
      interactions was studied at pH 6.0. Series of pectins were used, prepared from
      virtually fully esterified pectin by gradual de-esterification with alkali or
      with pectinesterase from oranges. Further amidated and acetylated pectins were
      also tested. The greatest interaction with BA was found with a very highly
      esterified pectin under in vitro conditions. The interaction diminished with
      decreasing degrees of esterification (DE). This decrease was more intensive for
      pectins possessing a blockwise arrangement of free-COOH groups. Derivatives of
      pectin generally interacted less with BA. These results were principally
      confirmed with commercial pectins, with pectins prepared on a pilot-plant scale
      and with pectins originating from a defined botanical source. The interactions of
      these preparations with BA were less intensive than with those of pectins having
      an ideal random distribution of free -COOH groups in the polysaccharide molecules
      at the same DE. The interaction with pectin is also likely to be influenced by
      the structure of BA.

PMID- 8525708
TI  - Use of UV photography to identify aflatoxin-producing strains of Aspergillus
      flavus and A. parasiticus.
AB  - UV photography in glucose, yeast extract (GY) agar medium was tested as a simple
      and rapid method for the distinction of aflatoxin-positive from aflatoxin
      negative strains of Aspergillus flavus and A. parasiticus. In the UV photographs
      aflatoxin-producing moulds were identified as grey or black colonies, whereas
      aflatoxin-nonproducing moulds appeared as white colonies. Of the aflatoxin
      positive strains detected by the UV photographic method, 10% was confirmed by
      extraction of the GY agar medium and mould mycelium in chloroform, extracts which
      were analysed subsequently using thin-layer chromatography. Confirmation of
      aflatoxigenic strains was achieved by biosynthesis on liquid medium yeast extract
      sucrose (YES) broth.

PMID- 8525709
TI  - [Consumption of calcium-rich food in the adult population of French-speaking
      Switzerland and of Tessin].
AB  - Food intake high in calcium content is important in the development of skeleton
      and the prevention of osteoporosis. From a public health perspective, it is
      therefore important to know the dietary calcium intake of a population. Two
      population surveys in the French and Italian parts of Switzerland (MONICA, 1988
      1989, and Geneva, 1991), were combined to study nutritional habits related to
      calcium intake. A random population sample, aged 35 et 65 years, answered to a 24
      hour recall questionnaire, either self-administered (MONICA, cantons of Vaud,
      Fribourg and Tessin, N = 2734) or by phone (canton of Geneva, N = 475). In the 4
      cantons, for the previous day, 60% of participants ate dairy products,
      particularly whole milk and cheese. They drunk 3-4 dl/day of milk. A significant
      proportion (10%) of french and italian speaking Swiss did not consume any food
      high in calcium content. In Geneva, the mean daily calcium intake was 656 mg in
      men and 489 mg in women. In conclusion 1) eating habits related to calcium intake
      are similar across cantons; 2) women consume dairy products more frequently than
      men, but in smaller quantities; 3) about 60% of men and 80% of women do not get
      the daily amount of calcium recommended for the prevention of osteoporosis.

PMID- 8525710
TI  - Review of the multiple chemical exposure factors which may disturb human
      behavioral development.
AB  - Previous research both in humans and laboratory animals provides evidence that
      prenatal exposure to metals, pollutants and drugs may impair the neurobehavioral
      development of the offspring. This may induce mental and psychomotor disturbances
      as well as learning, behavioral and sensory disorders. However, proof for a
      strict causality between some low-level exposures to chemicals and behavioral
      developmental dysfunctions, is often considered still not to be established. The
      pertinent studies on neurobehavioral developmental toxicity of individual
      substances (lead, cadmium, organic solvents, PCBs, alcohol, nicotine, diazepam)
      are reviewed, and the methodologies and conclusions, the missing aspects and the
      existing problems which still need to be solved in further studies, are
      discussed. In addition, the necessity of undertaking a broad prospective cohort
      study on multifactorial influences on the behavioral development of children is
      emphasized.

PMID- 8525711
TI  - Measuring cardiovascular disease risk factor levels: international comparisons
      between Bremen-north/west (Germany) and two southeastern New England (USA)
      cities.
AB  - Cardiovascular disease risk factor comparisons were made on study populations
      from communities in two different countries with similar ongoing intervention
      programs. Baseline survey data from the intervention and comparison communities
      of the Pawtucket Heart Health Program in Pawtucket, Rhode Island, and from the
      intervention Region of Bremen-North/West of the German Cardiovascular Prevention
      Study were compared with respect to these cardiovascular disease risk factors:
      smoking, overweight, physical inactivity, hypertension, and hypercholesterolemia.
      The relationship between these variables and social class was also examined in an
      attempt to partially explain some of the cross cultural differences in risk
      factors and predicted CHD and CVD mortality. Results indicated statistically
      significant differences in amount of cigarettes smoked, exercise frequency, diet,
      body mass index, total cholesterol, HDL, and blood pressure. These risk factors
      were generally higher in the German population than in the American population as
      were the predicted CHD and CVD mortality. For the study populations of both
      countries, however, the lower the social class, the more prevalent the smoking,
      excess weight, and lack of physical activity.

PMID- 8525712
TI  - [Pharmacotherapy aspects during Harrington's method of spinal surgery].
AB  - The cases of 85 patients with spinal deformation (m:22, f:63; age: 21.6 +/- 12.9
      y.) who underwent the spondylodesis according to Harrington were analysed
      retrospectively to evaluate the need of pharmacological treatment in the
      perioperative phase. Central analgetics such as pethidine, piritramide and
      pentacocine were prescribed most frequently. Propyphenazone containing
      formulations were the preferred peripheral analgetics. Sedation with
      benzodiazepines and neuroleptic was used regularly. Flucloxacillin and gentamicin
      were the flavoured antibiotics for perioperative prophylaxis. Impaired motility
      of the GIT-tract was treated with drugs such as carbachol or dexpanthenol.

PMID- 8525713
TI  - Concomitant natural infection with L. donovani and L. major: a case report from
      Iraq.
AB  - This is a case report of kala-azar with cutaneous leishmaniasis. Upon admission,
      the patient had fever, hepatosplenomegaly and an ulcer on her cheek. The patient
      responded to Pentostam. Isoenzyme studies of parasite isolates from the bone
      marrow and from the cutaneous lesion revealed that these were L. donovani and L.
      major, respectively. This is the first report in Iraq of a proven concomitant
      infection with two species of leishmania parasites.

PMID- 8525714
TI  - Trends of AIDS incidence in Europe and the United States.

PMID- 8525715
TI  - [The problem of the interferon therapy of patients with chronic viral hepatitis].
AB  - In this work the results of the clinico-immunological evaluation of the
      therapeutic effectiveness of alpha-interferon preparations are presented and
      criteria suitable for use in screening patients with chronic virus hepatitis,
      sensitive to interferon therapy, are discussed. The study revealed that the use
      of alpha-interferon preparations in single doses of 1-3 x 10(6) in a prolonged
      course of treatment (6-12 months) facilitated essential improvement in the
      clinical course of the disease and ensures correction of the immune status in
      55.6% of patients with chronic active hepatitis (CAH) resulting in cirrhosis of
      the liver and 57.9% of patients with CAH moderate activity. Indications for the
      use of alpha-interferon preparations in patients with CAH-induced cirrhosis were
      high activity of the cytolytic process, the presence of immunodeficiency, faintly
      pronounced autoimmune process and the presence of protein shifts.

PMID- 8525716
TI  - [Thymus hormones in the treatment and prevention of flavivirus infection under
      experimental conditions].
AB  - The evaluation and selection of the preparations of thymic hormones for the
      treatment and prophylaxis of acute tick-borne encephalitis (TBE) caused by Far
      Eastern TBE virus strains have been carried out on mice under different
      experimental conditions. These virus strains, highly and faintly virulent with
      respect to noninbred mice, produce a different modulating effect of the immune
      responsiveness of the host, respectively suppressing or simulating immune
      response to sheep red blood cells. A high prophylactic effect produced by thymic
      hormones (having protective index equal to 50-67%) with respect to highly
      virulent TBE virus stains has been established, which is seemingly indicative of
      the fact that such course of TBE leads to the formation of the state of severe
      immunodeficiency due to the lesion of the thymus. A high therapeutic effect
      resulting from the clinical use of thymic hormones is suggested.

PMID- 8525717
TI  - [Acute intestinal infections and hypertension].
AB  - Some data on the specific features of the clinical course of acute enteric
      infections (AKI) and hypertensive disease (HD) are presented. The data indicate
      that the pathogenetic mechanisms of these diseases often act on the same points
      and in some cases in the same direction. 32,448 AEI patients were placed under
      observation, among them 29,398 patients with alimentary toxicoinfections and
      3,050 patients with salmonellosis. Of these 1,483 patients had HD of stages II
      and III. In 266 patients of this group hypertensive crises of types I and II
      developed. In 128 AEI patients acute disturbances in cerebral blood circulation
      were observed. In 67.2% of cases these patients were found to have HD in their
      medical history. The treatment of patients with the combination of AEI and HD
      included rehydration with polyionic crystalloid solutions and the administration
      of hypotensive preparations.

PMID- 8525718
TI  - [The assessment of the cellular indices of the immune status in patients with
      chronic forms of hepatitis B].

PMID- 8525719
TI  - [Radioimmune analysis: the scientific and methodological procedures for its
      realization].

PMID- 8525720
TI  - [The language of the epidemiologist: an attempt at unification].

PMID- 8525721
TI  - [The mechanism of the development of nonspecific immunosuppression in viral
      infections].

PMID- 8525722
TI  - [The epidemiological markers of Pseudomonas aeruginosa strains circulating in
      different types of hospitals].
AB  - Pyocinovar and serovar characteristics of 91 P.aeruginosa strains isolated from
      patients and the environment in a hospital for premature children, a child survey
      hospital and a neonatological hospital. The leading epidemiological markers of
      P.aeruginosa strains, among them pyocinovar 883722, serovar 6 (a hospital for
      premature children), pyocinovar 888888, serovar 4 (a child surgery hospital),
      pyocinovars 888888 and 861322 (a neonatological hospital).

PMID- 8525723
TI  - [The activation of Yersinia pestis "murine" toxin and endotoxin by hemolyzed
      erythrocytes from mammalian blood].
AB  - Y. pestis "mouse" toxin and endotoxin have been found to be capable of being
      activated with hemolyzed mammalian red blood cells. The LD50 of the activated
      endotoxin decreases 5-10 times in comparison with the initial preparation. The
      LD50 of the activated "mouse" toxin decreases 5 times. As revealed in this study,
      the joint introduction of nonlethal doses of "mouse" toxin and endotoxin is
      highly toxic for white mice and guinea pigs. The presence of both "mouse" toxin
      and endotoxin in the toxic mixture is an essential factor for these two species
      of animals.

PMID- 8525724
TI  - [The effect of individual serum proteins and native blood serum on the adhesion
      of Staphylococcus aureus to cells in vitro].
AB  - Blood serum and its components were found to produce an antiadhesive effect which
      inhibited the attachment of S.aureus to cells HEp-2 and immortalized astrocytes.
      Normal and antistaphylococcal immunoglobulins exhibited the highest activity,
      inhibiting the process of bacterial adhesion in a serum-free medium. The
      antiadhesive activity level of native serum was considerably lower and
      constituted 4% of that of normal immunoglobulin and 85% of that of albumin. In
      spite of pronounced inhibiting action of normal immunoglobulin and albumin, their
      dissolution in serum did not increase its antiadhesive activity.

PMID- 8525725
TI  - [Streptococcus pneumoniae adhesion].
AB  - The adhesive capacity of 425 S.pneumoniae strains (S- and R-forms) isolated from
      children with various clinical forms of pneumococcal infection was studied with
      the use of the epithelium of oral cavity as a model. The strains isolated from
      patients with meningitis and otitis appeared to be less adhesive than the strains
      isolated from mucous membrane of respiratory tracts. In all clinical forms of
      infections the adhesive capacity of S.pneumoniae S-forms was significantly lower
      than that of R-forms. The hyaluronidase activity and the adhesive capacity of
      S.pneumoniae strains were found to be inversely related.

PMID- 8525726
TI  - [The protective activity of the adhesion pili of Yersinia pestis].
AB  - Y. pestis adhesion pili (AP) in the native form and in the subunit form, used for
      immunization in one or two injections in a dose of 12-100 mu g on aluminum
      hydroxide, did not protect white mice and guinea pigs from experimental Y. pestis
      infection. The study revealed that AP produced a pronounced cytotoxic effect on
      macrophages and practically no influence on leukocytes. This result was confirmed
      in the study of luminol-dependent chemiluminescence and in the analysis of 5'
      nucleotidase activity of phagocytes. These data make it possible to regard AP as
      Y. pestis antimacrophagal pathogenicity factor.

PMID- 8525727
TI  - [The characteristics of new species of pathogenic microorganisms in the genus
      Francisella].
AB  - The comparative study of newly discovered pathogenic bacteria of the genus
      Francisella was carried out with the use of a complex of microbiological and
      serological methods. While having great similarity to the causative agent of
      tularemia, F. novicida, F. novicida-like bacteria and F. philomiragia had lesser
      growth requirements, some specific morphological and structural features, were
      capable of fermenting sucrose and exhibited low pathogenicity to experimental
      animals. The strains under study proved to be virulent with regard to golden
      hamsters, who were for this reason proposed as an adequate model for the
      isolation of these bacteria from environmental objects and pathological material
      obtained from patients. The use of immunoblotting made it possible to find out
      that all Francisella species had protein antigens, similar to their
      electrophoretic mobility and serological activity.

PMID- 8525728
TI  - [The ontogeny of the cell receptors of the adhesion of meningococci and influenza
      viruses].
AB  - Specific age and individual features of the adhesion of Neisseria meningitidis,
      groups A, B and C, and influenza viruses, types A and B, to red blood cells of
      humans aged 0-60 years were studied. The study revealed that the red blood cells
      of newborns, in contrast to those of persons of older age groups, are highly
      resistant to N. meningitidis adhesion, but highly sensitive to the adhesion of
      influenza viruses, though to a varying degree. The postnatal period of
      ontogenesis is characterized first by a sharp rise (up to 1 month) and then by a
      slower increase of the individual sensitivity of red blood cells to
      N.meningitidis adhesion without essential changes in the sensitivity of the same
      cells to the adhesion of influenza viruses.

PMID- 8525729
TI  - [Pseudomonas pseudomallei and Pseudomonas mallei--capsule-forming bacteria].
AB  - The specific features of the submicroscopic structure of the causative agents of
      melioidosis and glanders, grown in culture media and at the initial stages of
      experimental infection in guinea pigs and golden hamsters, were studied with the
      use of electronic cytochemistry and immunocytochemistry. P. pseudomallei and P.
      mallei were found to be capsule-forming bacteria. According to the data obtained
      with the use of electronic cytochemistry, the basis of the capsular substance P.
      pseudomallei and P. mallei is formed by polysaccharide biopolymers protecting
      these bacteria from phagocytosis.

PMID- 8525730
TI  - [The effect of the conditions of the controlled cultivation of Neisseria
      meningitidis on the lipopolysaccharide yield].
AB  - The preparations of lipopolysaccharide (LPS) were obtained from N.meningitidis
      cells grown in synthetic nutrient medium in a fermenter. Different N.meningitidis
      strains, groups A, B, C, were found to give different yield of the preparation of
      LPS: the maximum yield was obtained from N.meningitidis cells C 133 and the
      minimum yield, from N.meningitidis cells B 125. The comparison of group B strains
      125 and 150 showed that the former gave a higher yield of LPS. The influence of
      the phase of growth on the yield of the preparation of LPS obtained from
      N.meningitidis cells 125 was shown to be manifested under the conditions of
      oxygen excess; in the exponential phase the highest yield of the preparation was
      observed. Oxygen dissolved in the medium was found to influence the yield of the
      preparation of LPS: with the same content of glucose in the medium the yield of
      LPS was higher under the conditions of the limited concentration of oxygen; with
      the same concentration of oxygen in the medium the yield of LPS increased with
      the increase of the concentration of glucose.

PMID- 8525731
TI  - [The serosubtyping of serogroup B meningococci].
AB  - The results of the study of 116 Neisseria meningitidis strains, isolated from
      patients at different territories of Russia at the period of 1983-1992, by the
      method of the enzyme immunoassay are presented. 13.8 +/- 3.2% of the strains were
      found to have stereotype proteins and 59.5 +/- 4.5%, subtype proteins. In the
      population of circulating meningococcal strains no absolute prevalence of any
      single serotype or subtype was established. The comparison of the tendency in the
      course of morbidity rate and the state of the serosubtype composition of isolated
      group B N. meningitidis stains is indicative of the favorable situation with
      respect to meningococcal infection and the importance of further observation of
      the circulating strains.

PMID- 8525732
TI  - [Improvement in the species identification of Lactobacillus by using microculture
      test systems and data on its genome structure].
AB  - 18 microanalytical media, used for the construction of a biochemical plate test
      system permitting the specific identification of bacteria of the genus
      Lactobacillus, were developed on the basis of data on the metabolic activity of
      these bacteria and their need of growth factors. As the results of studies made
      on 78 Lactobacillus strains with the use of traditional microbiological and gene
      systematizing methods, the proposed test system was shown to be reliable and
      specific.

PMID- 8525733
TI  - [The deamination of L-arginine and the synthesis of active nitrogen compounds in
      Yersinia pestis].
AB  - Y. pestis were found to be capable of highly effective deamination of L-arginine
      with the formation of citrulline and the synthesis of active nitrogen compounds.
      The formation of citrulline by the cells of initial strains and arginine
      dependent derivatives with the blocking of the synthesis of arginine on the level
      of ArgG, ArgF and ArgE was shown. The temperature of incubation, the
      concentration of hydrogen ions (pH) and the presence of exogenic L-arginine were
      found to produce a regulatory effect on the intensity of the process of
      deamination. The products of arginine decomposition are supposed to play a
      pathogenetic role in Y. pestis infection.

PMID- 8525734
TI  - [The presence of HIV DNA in the neutrophils of persons infected with the human
      immunodeficiency virus and the clinical parallels of this phenomenon].
AB  - Relationships between some clinical data and the detection of human
      immunodeficiency virus (HIV) DNA in polymorphonuclear neutrophils (PMN) of 37 HIV
      infected persons were studied. HIV DNA was determined with the use of polymerase
      chain reaction. The level of HIV DNA in PMN, sufficient for determination, was
      mostly detected in persons with clinical manifestations of HIV infection and less
      frequently in asymptomatic patients (46.7% and 18.2% respectively, p < 0.05). The
      significant relationship between the presence of HIV DNA in NP and a decrease in
      the CD4/CD8 ratio, as well as an increase in the level of immunoglobulins in the
      blood serum, has been established. The presence of HIV DNA in PMN was positively
      related to the decrease of the functional activity of these cells and the level
      of PMN in peripheral blood. The infection of PMN with HIV may be one of important
      mechanisms of their damage in HIV infection.

PMID- 8525735
TI  - [The effect of the blood serum factors of HIV-infected persons on the functional
      activity of the neutrophils in healthy donors].
AB  - The influence of 64 blood serum samples from HIV-infected patients at different
      stages of the infection on the functional activity of polymorphonuclear
      neutrophils (PMN) of 9 healthy donors was studied. In this study an increase in
      the production of oxygen radicals by PMN of the donors was revealed (in the
      chemiluminescence test), positive correlations between this increase and stages
      of HIV infection were followed. The presence of HIV-positive serum in the
      incubation medium led to the inhibition of phagocytosis and produced almost no
      changes in the capacity of PMN for its completion. A decrease in phagocytosis
      correlated with the level of complement and did not depend on other serum
      factors; on the contrary, an increase in chemiluminescence was not linked with
      the levels of complement, but had correlative relationships with the levels of
      anti-HIV antibodies and circulating immune complexes.

PMID- 8525736
TI  - [The characteristics of the epidemiology of campylobacteriosis under modern
      conditions].
AB  - The results of the clinico-epidemiological study of campylobacteriosis in a
      concrete area (Kiev and the Kiev region) are presented. The proportion of
      campylobacteriosis cases was found to be 6.4% among patients hospitalized in
      connection with acute enteric infections. Hens were most frequently the source of
      human infection. Thus, at the local poultry farm the proportion of hens
      contaminated with bacteria of the genus Campylobacter was 44.8%. The possible
      routes of the spread of Campylobacter infection and the factors of its
      transmission were established. The most important element of the epidemiological
      marking of Campylobacter bacteria is the determination of their species and
      serotype.

PMID- 8525737
TI  - [The epidemiological surveillance of hospital infections linked to methicillin
      resistant Staphylococcus aureus].
AB  - As revealed in the realization of the epidemiological surveillance of hospital
      infections caused by methicillin-resistant S. aureus (MRSA) in different types of
      hospital, MRSA strains causing purulent inflammatory diseases belong to different
      clones. The complex marking of MRSA made it possible to determine the presence of
      the same clone in different hospitals and to detect the outbreaks of hospital
      infections caused by different clones of MRSA in one hospital. It was found
      necessary to supplement the commercial international phage-typing set with pages
      permitting the detection of the specific system of restriction-modification in
      MRSA.

PMID- 8525738
TI  - [A deficient T-cell count and its elimination during the treatment and prevention
      of infections].
AB  - The results of the study of the parameters of the immune system in persons
      suffering from frequent infections, bacteriocarriers and persons with nonspecific
      infections are presented. The study revealed that T-cell deficiency of the 2nd
      and 3rd degrees could be regarded as the universal marker of decreased immune
      reactiveness. Sodium nucleinate was found to be capable of stimulating the T-cell
      element of immunity and antibody formation, which made it possible to achieve a
      considerable decrease in morbidity rate. Sodium nucleinate was shown to be highly
      effective in the prophylaxis of acute respiratory viral infections, carrier state
      and in the sanitation of purulent foci of infection.

PMID- 8525739
TI  - [The cellular mechanisms of antianthrax immunity].
AB  - The influence of the vaccination of mice and volunteers on the activity of
      natural killer cells (NKC) and K cells, the effectors of natural and antibody
      dependent cytotoxicity of cells, was studied. Both types of killer cells were
      found to take an active part in the vaccinal process during the whole term of
      observation. The changes revealed in this study were characterized by two phases.
      At the first contact with the antigen a rise in the activity of killer cells was
      observed; this rise was then followed by their pronounced suppression, reflecting
      total structural changes which occurred in the infected macroorganism. Repeated
      injections of the antigen induced mainly the activation of K cells. The use of
      protective antibodies contained in the commercial preparation of antianthrax
      globulin exerted influence on the duration of changes in the activity of NKC and
      K cells of the infected animals.

PMID- 8525740
TI  - [Primers for the genus-specific detection of Francisella tularensis in the
      polymerase chain reaction].
AB  - Primers for the detection of F.tularensis in the polymerase chain reaction (PCR)
      have been obtained. The method of PCR permits the identification of up to 10
      F.tularensis cells in the analysis of pure and mixed cultures, as well as
      suspensions prepared from the organs of laboratory animals. The possibility of
      the simultaneous analysis of several samples makes this system for the detection
      of F.tularensis useful for epidemiological investigations.

PMID- 8525741
TI  - [The use of gnotobiological technology for producing and maintaining
      experimental, animals with different microbiological states of the intestines].
AB  - The standardization of all components ensures the optimum experimental
      conditions; for this reason the obtaining and maintenance of animals meeting GLP
      requirements is one of the development of scientific research in biology and
      medicine. The aim of the present work was the study of the possibility of using
      gnotobiological technology for obtaining animals with different microbial status
      of the intestine and their maintenance. Our investigations revealed that
      obtaining animals with different microbial status of the intestine and their
      maintenance under the conditions of total gnotobiological isolation (TGBI)
      prevented the contamination of the animals, thus facilitating the standardization
      of research procedures. Gnotobiological technology made it possible to create the
      optimum maintenance conditions and to ensure constant microbial status in
      animals, free from pathogenic flora. The maintenance to totally decontaminated
      mice under TGBI conditions ensured the total germ-free status in these animals
      for 9 days.

PMID- 8525742
TI  - [Yersinia pseudotuberculosis in a model marine ecosystem (experimental
      research)].
AB  - Materials on the behavior of Y. pseudotuberculosis in the model of marine
      ecosystem are presented. Y. pseudotuberculosis, both carrying and having lost the
      virulence plasmid of 45 MD, die in nonsterile sea water, but are capable of
      prolonged survival in sterile sea water and in the bodies of echinoderms. The
      death of these bacteria is accelerated in the presence of larvae of echinoderms.
      In sea water at low temperature Y. pseudotuberculosis maintained their high
      pathogenicity potential which they use on contact with eukaryotes. Under these
      conditions Y. pseudotuberculosis preserve their virulence plasmid, thus causing
      the disease and death of animals.

PMID- 8525743
TI  - [The comparative characteristics of the vaginal microflora in parturient women
      who are carriers of Streptococcus serogroup B and in those who are free of
      carriage].
AB  - In the study of vaginal microflora in parturient women, carriers of group B
      streptococci (GBS), and those free of carriership a wide range of microorganisms,
      represented by aerobic and anaerobic species with the prevalence of lactobacteria
      in both groups of women, was isolated. The composition of vaginal microflora in
      parturient women did not depend on the presence of GBS in this biotope or on the
      level of colonization by lactobacteria. The colonization resistance (CR) of the
      vaginal mucosa had essential influence of the level of carriership with respect
      to GBS and a number of representatives of the symbiotic microflora of this locus.
      In the majority of cases GBS were isolated from parturient women with low CR.

PMID- 8525744
TI  - [The experimental validation of methods for the emergency immunoprophylaxis of
      gas gangrene].
AB  - The effectiveness, both immunological (by an increase in the titers of
      antitoxins) and protective (by resistance to the inoculation of the absolute
      lethal dose of infective agents), of the regional (wound) revaccination with
      tetratoxoid (Clostridium perfringens, C. oedematiens, C. septicum, C.
      histolyticum) was demonstrated on the experimental model of wound infection (gas
      gangrene) of guinea pigs. The schedule of rapid immunization with tetratoxoid was
      developed, which made it possible to create good immunological preparedness
      (basic immunity) for subsequent revaccination in case of traumas within 6 days.
      The effectiveness of rapid immunization by the application of tetratoxoid on the
      wound was shown. This immunization ensured a considered increase in the titers of
      antitoxins within the first 6 days, which increased the protection of the animals
      from infection with each of the four causative agents of gas gangrene.

PMID- 8525745
TI  - [Urogenital mycoplasmosis and Mycoplasma carriage during pregnancy and in
      inflammatory processes of the genitalia in workers in the electronics industry].
AB  - To find out the spread of urogenital Mycoplasma carriership urogenital
      mycoplasmosis (UGM) among women living and working under similar conditions and
      making up risk groups with respect to these infections, pregnant women,
      gynecological patients and clinically healthy women were specially surveyed. As
      revealed in this survey, UGM and Mycoplasma carriership were found in clinically
      healthy female workers significantly more often than in other similar groups of
      the same region. In the group of pregnant women the occurrence of Mycoplasma
      carriership and UGM reached 90%. In cases of sterility the facts of asymptomatic
      Mycoplasma carriership and UGM were registered.

PMID- 8525746
TI  - [The laboratory diagnosis of mycoplasmosis and ureaplasmosis in urological and
      gynecological patients].
AB  - The survey of 630 patients with urogenital pathology, habitual miscarriage and
      sterility revealed that they were mostly (91-100%) infected with M. hominis
      and/or U.urealyticum. This fact indicates the necessity of organizing the
      epidemiological control of these infections. It is expedient to use the complex
      of laboratory methods for diagnosing these infections through the effectiveness
      of such methods may vary in different nosological forms. Thus, colpitis and
      nonspecific urethritis were shown to be most effectively diagnosed by the
      serological methods.

PMID- 8525747
TI  - Reconstruction of the mandible with vascularized iliac crest flap--initial
      experience at the Tata Memorial Hospital.
AB  - Resection of the mandible for cancer of the oral cavity can result in gross
      functional and aesthetic deformity. Inspite of technological advances,
      reconstruction of mandibular defects remains one of the most challenging
      procedures in head and neck surgery. Conventional methods like alloplastic
      implants and bone grafting have a high rate of failure. The advent of
      microvascular techniques for mandibular reconstruction has revolutionised the
      management of these patients. We present our initial experience based on 18
      patients who underwent vascularised iliac creast transfer at the Tata Memorial
      Hospital between November, 1992 and January, 1994. The operative technique of
      raising, shaping and fixation of the iliac crest flap as well as advantages and
      disadvantages are discussed. Postoperative graft viability was assessed using
      99mTc-MDP scans during the 1st, 3rd and 12th weeks after surgery. We lost 3 flaps
      (16.4%) due to uncontrolled infection and vessel thrombosis. All of the remaining
      patients demonstrated good uptake on bone scans and satisfactory bony union on
      OPG. We conclude that mandibular reconstruction using the vascularised iliac
      crest is reliable and produces acceptable postoperative functional results with
      88% of patients having no swallowing difficulty, 83% with normal speech and
      excellent cosmesis in 83% (15/18) of the patients.

PMID- 8525748
TI  - The indications and the plan of plastic operations in children with Down's
      syndrome.
AB  - During the past ten years (1984-1993), 52 children with Down's syndrome aged 3-16
      years were treated surgically at the Department of Plastic Surgery at the Medical
      University of Lodz. The authors present the indications and the treatment plan in
      selected patients, the optimal timing of surgical treatment, the choice of
      surgical methods for the correction of facial deformity and for the limpness of
      tongue depending on its form and intensity. Elimination of mongoloid features of
      the face (tongue, lower lip, eyelids, nose) has a positive influence on
      rehabilitation of children with Down's syndrome. This procedure was used in
      Poland for the first time.

PMID- 8525749
TI  - Possible complications of sagittal osteotomy of the mandibular ramus.

PMID- 8525750
TI  - Our long-term experience and results of surgical management of the carpal tunnel
      syndrome.
AB  - On the basis of 2,867 surgical revisions in individuals with the diagnosis of the
      Carpal Tunnel Syndrome performed in 1975-1994 were determined principles for the
      indication of surgical treatment and the choice of surgical technique and
      postoperative care. Underlined was the surgical method of n. medianus revision
      within the palm in the aim to prevent the development of a painful scar due to
      the injury of the ramus palmaris nervi mediani. Finally was mentioned the
      beneficial effect of soft laser on the scar exerted during the postoperative
      period.

PMID- 8525751
TI  - Our experience with reoperations for the diagnosis of the carpal tunnel syndrome.
AB  - On the basis of the analysis of the results obtained and of the surgical findings
      during reoperations for the diagnosis of the Carpal Tunnel Syndrome it is
      recommended to perform a reoperation in cases of primary failure. Underlined is
      the surgical approach with the use of a prolonged incision, as well as an
      adequate postoperative care.

PMID- 8525752
TI  - Therapeutic possibilities in soft tissue defects on the dorsum of fingers.
AB  - The present report deals with the therapeutic possibilities of the management of
      deep defects of soft tissues on the dorsum of fingers. In addition to the
      commonly used methods are presented two less common procedures which are in
      certain cases less time consuming and provide more comfort both to the patient
      and to the surgeon.

PMID- 8525753
TI  - Adduction contraction of the thumb.
AB  - Adductive contraction of the thumb reduces markedly the grip function of the
      hand. It develops after an inadequate management of injuries within the 1st
      interdigital space, because of the oedema associated with injuries of other parts
      of the hand, after burns, or due to an inborn malformation. The authors discuss
      the possibilities of the surgical management and the necessity of an adequate
      postoperative rehabilitation.

PMID- 8525754
TI  - Early rehabilitation of the hands after the suture of flexors and after tendon
      grafts with the use of dynamic splints.

PMID- 8525755
TI  - Skeletal muscle capillary ultrastructure in Toxoplasma gondii parasitized mice.
AB  - A light and transmission electron microscopic study was performed in skeletal
      muscles from mice experimentally infected with Toxoplasma gondii. Parasite cysts
      were not observed. Capillary endothelial cytoplasm abnormalities included
      proliferation of organelles, decrease of pynocytic vesicles, degenerative changes
      and necrosis. In some capillaries the lumen was reduced or absent. Pericytes also
      were altered. In all animals (n = 13), the basement membrane was normal. The
      cellular infiltrate consisted of macrophages, lymphocytes, mastocytes and
      eosinophils. The alterations observed in muscle microvasculature in absence of
      Toxoplasma gondii cysts, could be due to a host-immune response to the parasite.

PMID- 8525756
TI  - [Desensitization of the nicotinic acetylcholine receptor].
AB  - In biological membranes, ionic channels act speeding up ion movements. Each ionic
      channel is excited by a specific stimulus (i.e. electric, mechanical, chemical,
      etc.). Chemically activated ionic channels (CAIC), such as the nicotinic
      acetylcholine receptor (nAChR), suffer desensitization when the receptor site is
      still occupied by the agonist molecule. The desensitized CAIC is a non functional
      channel state regarded as a particular case of receptors rundown. CAIC
      desensitization only involve reduced activity and not their membrane elimination.
      Desensitization is important to control synaptic transmission and the development
      of the nervous system. In this review we discuss results related to its
      production, modulation and some aspects associated to models that consider it.
      Finally, an approach combining molecular biology and electrophysiology techniques
      to understand desensitization and its importance in biological systems is
      presented.

PMID- 8525757
TI  - A behavioral treatment program as a therapy in the control of primary
      hypertension.
AB  - In order to assess the effects of a Behavioral Treatment Program in the control
      of primary hypertension, twenty one unmedicated hypertensives were randomly
      allocated to three groups: first, a treatment group (BHG) receiving a Behavioral
      Treatment which included: deep muscle relaxation, peripheral temperature
      Biofeedback and anxiety management training; second, the placebo attention
      control group (PHG) and third, a control group of hypertensives too (CHG).
      Additionally, were compared with seven normotensives subjects (CNG). The post
      treatment measures showed a significant reduction (p < 0.001) in systolic and
      diastolic values only in the (BHG). In a six months follow-up the (BHG) group
      still showed a significant reduction in the systolic and diastolic BP (p < 0.02;
      p < 0.01). Moreover individual variations in response to treatment were observed
      in this group, (BHG).

PMID- 8525758
TI  - Changes produced by experimental hypothyroidism in fibre type composition and
      mitochondrial properties of rat slow and fast twitch muscles.
AB  - Experimental hypothyroidism changes the fibre type percentual composition of
      soleus and extensor digitorum longus muscles of rat. In both cases it has been
      observed an increase in the type I and a decrease in the type II fibre
      percentages. A reduction of proton passive permeability of mitochondrial membrane
      is observed in experimental hypothyroidism together with a decrease in the
      docosahexaenoic acid content of the mitochondrial total lipids. This change in
      the lipid composition could produce the reduction of the mitochondrial membrane
      proton passive permeability and thus, reduces state 4 mitochondrial respiratory
      rate of rat skeletal muscles.

PMID- 8525759
TI  - [Esophageal stenosis in children. Etiology, pathogenesis, and diagnosis (part
      I)].

PMID- 8525760
TI  - [Strongyloides stercoralis. Report of a case and review of the literature].
AB  - A fatal case of strongyloidiasis in a boy aged 8 months, referred to our
      hospital, with severe malnutrition, dehydration, brownish fluid through the naso
      gastric tube and relapsing chronic diarrhea with bloody mucus. Through all
      symptoms and observation of rabditoid larvae, eggs and even adult females,
      parasitologic diagnosis was achieved. In spite of medical intensive care the
      patient died after 18 days of hospitalization. Disease's pathophysiology is
      discussed as well as a review about the trustfulness of the parasite biological
      cycle as is traditionally described in the literature. Ability is questioned of
      rabditoid larvae to follow the alternative way as free living adults or parasitic
      living in adults.

PMID- 8525761
TI  - [Prognostic factors in pathology: its current value].

PMID- 8525762
TI  - [Expression of MIB-1/KI-67 and bcl-2 in gastric carcinoma. Relationship with
      clinico-pathological factors].
AB  - Neoplastic development partly depends on a balance between cellular proliferative
      activity and the eventual suppression of the mechanism of apoptosis.
      Proliferative activity can be estimated by quantification of KI-67 antigen that
      appears during phases G1, S, G2 and M of the cellular cycle, whereas apoptosis is
      shown by the expression of the bcl-2 protein. In this study the expression of KI
      67 and bcl-2 antigens was examined in a series of 97 gastric adenocarcinomas, to
      find out their relations with different clinical and pathological factors. The
      results showed that the expression of KI-67 was only associated to histological
      grade and did not have any prognostic significance. On the other hand, there was
      a better 5 year survival rate when invasion did not go beyond the muscularis
      propria, there were no lymph node metastases, in the woman and when tumors were
      located in the antrum. bcl-2 protein was surprisingly negative in all cases
      albeit of previous descriptions of overexpression of this protein in cases of
      gastric dysplasia. It is postulated that expression of bcl-2 could appear at an
      early stage of gastric carcinogenesis and that only a small proportion of
      malignant tumors would maintain that overexpression.

PMID- 8525763
TI  - [New suggestions for the management of alcoholic liver diseases].
AB  - Some recent proposals in management of alcoholic liver disease are discussed
      focusing on early diagnosis and treatment of alcohol abuse itself, alcoholic
      hepatitis early mortality, clinical meaning of nutritional therapy, serological
      approach and treatment of hepatic fibrosis, and problems in liver transplantation
      for end stage alcoholic liver cirrhosis. CAGE or similar systematized brief
      questionnaires, and desialylated transferrin/total transferrin ratio as
      serological marker, seems to be interesting contributions to "hidden" alcohol
      abuse diagnosis and abstinence control while psycho-social support and voluntary
      incorporation to self-aid groups are the best weapons to reach persistent
      abstinence. Corticosteroids seems to improve survival in a selected group of
      patients with severe alcoholic hepatitis, specially in those presenting
      encephalopathy but free of GI bleeding, decompensated diabetes, active
      infections, pancreatitis, and other contraindications or adverse effects of these
      drugs. Relationship between direct toxicity and nutritional deficiencies in
      pathogenesis of alcoholic liver injury are not clear enough, but malnutrition is
      generally present in patients requiring hospitalization, and related to clinical
      severity; oral, enteral or parenteral nutritional supplementation in this order
      of preference according to patients condition, associated or not with steroid
      anabolics, are useful in cases with moderate to severe alcoholic hepatitis or
      decompensated cirrhosis to eliminate the catabolic state, reaching a better
      nitrogen balance and liver function tests, without special adverse effects. A
      special role on liver regeneration is discussed. Antioxidants and supernutrients
      are special "modern" aspects of nutritional therapy in alcoholic liver disease
      generally related to the MEOS activation in chronic alcoholism, the excessive
      production of free radicals, and the depletion of glutathione, membrane
      phospholipids (specially phosphatidycholine), and vitamin A, E, and C. Natural
      supplements as soybean polyunsaturated lecithin, with high concentration of
      phosphatidycholine, or oral supplementation with natural metabolic products
      depleted from the liver of chronic heavy drinkers, such SAMe, have an interesting
      rationale based on experimental and clinical findings besides availability and
      costs. Carotenoids and tocopherols supplementation seems to be an useful tool,
      but are limited in the case of vitamin A because its special toxicity in chronic
      alcoholism. Serological markers of metabolism of liver connective tissue are
      clearly involved in fibrogenesis process and other inflammatory connected events;
      standardization of laboratory methods surely will result in new possibilities of
      non-invasive valuation of liver injury, evolution and therapeutic response;
      special histological damage such as sinusoidal "cappilarization" (type i.v.
      collagen and laminin), endothelial sinusoidal cell function (seric hyaluronate),
      or collagenase activity (TIMP-1 or tissue inhibitor of metalloproteinases-1)
      seems to be valuable by these new technologies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8525764
TI  - [Detection and characterization of pre-core mutants of hepatitis B virus (HBV) in
      chronically infected patients].
AB  - Hepatitis B virus infection is responsible of an important number of world
      morbimortality. This is associated to severe liver outcome such as cirrhosis and
      hepatocellular carcinoma. Diverse factors influence the severity of liver injury
      produced by Hepatitis B Virus (HBV): the emergence of HBV mutants unable to
      secrete "e" antigen (pre-core mutants), the virus and host genetic heterogenicity
      and immune system competence. Particularly, the presence of pre-core mutants in
      chronic carriers is associated a low response to interferon therapy. We present
      paper is to present evidence as to the presence of these mutants in chronically
      infected, HBeAg negative patients (HBsAg positive) in Argentina. Viral DNAs were
      extracted from sera of nine patients, amplified by PCR and characterized by
      restriction enzyme assay. All of them appear to be pre-core mutants according
      with serological markers and a very low level of viral DNA detected in serum.
      Further genetic characterization of one of them by nucleotide sequence analysis
      of the pre-core region let allowed us to show modifications at codon 15 and 28
      both of them previously described for pre-core mutants.

PMID- 8525765
TI  - [Helicobacter pylori in patients with gastritis and gastric ulcer].
AB  - Seventy patients symptoms and signs compatible with gastritis and/or peptic ulcer
      were included in the study; they were 41 women and 29 men, with an age range of 9
      84 years, and they underwent upper endoscopy. Brushing of the antrum was
      performed and 4 biopsies were taken from it. With the gastric mucus, a smear was
      prepared for Gram staining; one sample of tissue was placed directly in urea
      medium and another tissue sample in Skirrow medium; and two samples of tissue
      were stained with Hematoxylin-eosin and examined under the light microscope.
      Those patients who were taking antibiotics capable of inhibiting growth of
      Helicobacter pylori (Hp), the last four weeks prior endoscopy, were excluded from
      the study. Twenty-six patients (37.1%) were positive (+) for Hp the culture in
      urea medium. Of these 26 patients, 15 (21.4%) were also positive by the Skirrow
      method, and 11 (15.7%) by Gram stain. Epigastric pain was the most predominant
      symptom in (+) patients (80.7%) and (-) patients (68.1%) for Hp. Superficial
      acute gastritis within the antrum was the most frequent endoscopic finding in (+)
      (84.6%) and (-) (68.1%) patients. Chronic superficial gastritis was the
      predominant microscopic finding in (+) (42.3%) and (-) (38.6%) patients as well.
      Microscopic examination was positive for Hp in 6 (23%) patients by H-E stain.
      According to these results, there was no statistically significant difference in
      symptoms, endoscopic and microscopic findings between positive and negative
      patients for Hp.

PMID- 8525766
TI  - [Changes in the surgical approach of impacted lithiasis in the terminal
      choledochus].
AB  - Transduodenal sphincterotomy used to be was a common procedure when the surgeon
      couldn't remove stones from the terminal choledochus. We treated 6 patients in
      whom instead of a sphincterotomy, the stone was left in place and the duct
      drained with a T-tube. The first three cases were so managed because an emergency
      left no other option in the other three the decision was elective. Operative
      cholangiographies showed the impacted stones and in the postoperative
      cholangiographies, the stones had passed down to the stones had moved upward
      because of the decompression with the T-tube. The problem in all five patients
      with residual stone was easily solved. In one patient the stone was moshed down
      to the duodenum with biliary irrigation. The other four underwent transfistular
      extraction. Reviewing the morbility of transduodenal sphincterotomy we concluded
      that in an impacted stone it has currently few indications. In this era of
      "Biliary Perestroika" and specifically in emergencies or surgeons not fully
      experienced in transduodenal sphincterotomies, to put a T-tube and in the
      postoperative period complete others non surgical methods is an acceptable
      criteria. Also this approach can be applied to laparoscopic surgery when the
      operative cholangiography shows an unexpected biliary duct stone. The technique
      of leaving a transcistic catheter followed in the postoperative period by other
      therapeutic methods maintained in the discussion, could avoid a conversion to
      laparatomy or a laparoscopic choledochotomy, technique still in a developing
      period.

PMID- 8525767
TI  - Treatment for adult acute myeloid leukemia: where we stand in 1995.

PMID- 8525768
TI  - [Etiology and pathogenesis of glycosylphosphatidylinositol anchor-linked membrane
      protein deficiency].

PMID- 8525769
TI  - [Use of DNA analysis for determining HLA class II antigens].

PMID- 8525770
TI  - [Interleukin 2 receptor (Il-2): structure and function].
AB  - Interleukin 2 and its receptor play a crucial role in the growth and
      differentiation of many cells such as lymphocytes T and B, NK cells, macrophages
      and monocytes. Il-2 receptor (Il-2R) is involved in Il-2 induced cellular
      signalling. We discuss the Il-2R structure, function of three distinct subunits
      and the complex pathways that link the cell surface receptor to the nuclear proto
      oncogene production.

PMID- 8525771
TI  - [Fludarabine in the treatment of chronic lymphocytic leukemia and other
      lymphoproliferative disorders].
AB  - Fludarabine, an analogue of arabinosyl adenine, used since 1986 proved to be a
      new agent effective particularly in chronic lymphocytic leukaemia. About 35% of
      patients refractory to previous cytostatic treatment and about 75% of untreated
      patients obtained complete remissions. Nearly 90% of them revealed no minimal
      residual disease and no relapse during 2 years of observation. Worse response was
      found in patients with other low grade non-Hodgkin's lymphomas.

PMID- 8525772
TI  - [Clinical pharmacology of all-trans retinoic acid (ATRA)].
AB  - All-trans-retinoic acid (ATRA, tretinoin) is a natural metabolite of retinol and
      is normally found in plasma, at concentrations of approximately 0.5-1.5 ng/ml.
      The in vivo and in vitro studies has demonstrated that in pharmacological doses
      it can differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA
      has been shown to induce complete remission (CR) rates of approximately 90% in
      newly diagnosed and first relapsing APL. However, CR induced by ATRA alone are
      usually not sustained and intensive antileukemic consolidation therapy is
      required to prolong remission. ATRA followed by intensive chemotherapy has
      improved the outcome of newly diagnosed APL, by increasing the CR rate and by
      reducing the risk of relapse. The presence of the PML/retinoic acid receptor
      alpha (PML/RAR-alpha) fusion gene is a marker for sensitivity to this agent. ATRA
      therapy is associated with the risk of rapidly rising leukocyte counts, leading
      to the retinoid acid syndrome which may be fatal if the increase in leukocytes is
      not reversed. A side effects from these complications ATRA therapy is generally
      well tolerated.

PMID- 8525773
TI  - [Effect of 2-chlorodeoxyadenosine, arabinoside cytosine and doxorubicin on acute
      myeloid leukemia clonogenic cell proliferation].
AB  - We examined the influence of 2-chlorodeoxyadenosine (2-CDA) in concentration 300
      nM/l alone and in combination with cytosine arabinoside (ara-C; 10(-7) M/l and
      doxorubicine (drb; 1 microgram/ml) on the proliferation of acute myeloid leukemia
      (AML) clonogenic cells (L-CFU) in agar/liquid culture system. After preincubation
      of blast cells with 2-CDA or ara-C as a single agent the number of colonies was
      reduced, reaching 70% of control (p < 0.05). Exposure of AML blasts to drb
      resulted in a greater reduction of L-CFU proliferation than in experiments with 2
      CDA or ara-C alone (p < 0.05). Coadministration of 2-CDA in conjunction with ara
      C or drb, and additionally with ara-C and drb caused the inhibition of L-CFU
      growth in comparison with control experiments by 52%, 78% and 61%, respectively
      (p < 0.05). In further experiments we studied the effect of ara-C and drb
      together with 2-CDA in different concentrations (20, 100 or 300 nM/l). After
      preincubation with 2-CDA in concentration 20 nM/l no change in blast colony
      formation was observed in relation to controls which comprised ara-C and drb only
      (p < 0.05). The increase of 2-CDA concentration to 100 or 300 nM/l in combination
      with ara-C and drb significantly reduced the growth of AML clonogenic cells (p <
      0.05). The greatest, 90%, inhibition of L-CFU proliferation was observed after
      the exposure of blast cells to ara-C, drb and 2-CDA in concentration 300 nM/l (p
      < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8525774
TI  - [Comparison of platelet and leukocyte content in platelet concentrates obtained
      from CS-3000 and third generation (CS-3000 plus and Cobe-Spectra) cell
      separators].
AB  - Platelet concentrates (PCs) obtained using old generation of cell separators
      contain high number of leukocytes. White cell (WBC) contamination and platelet
      (Plts) number in PCs obtained from separator II-nd generation CS-3000 and
      separators III-rd generations CS-3000 plus and Cobe-Spectra have been determined.
      PCs from new separators contain the same Plts number as PCs from CS-3000. The
      average leukocyte count in PCs obtained from CS-3000 was 171.26 x 10(6), whereas
      WBC number in PCs from CS-3000 plus and Cobe-Spectra were 2.87 and 2.54 x 10(6)
      respectively. In about 85% of PCs obtained from III-rd generation cell separators
      the leukocyte count did not exceed 5 x 10(6). This count is considered sufficient
      to prevent alloimmunization of HLA antigens. The determination of WBC count in
      every PCs allows to select PCs with fewer than 5 x 10(6) leukocytes and to
      transfuse them without the necessity of using expensive filters for leukocyte
      removing.

PMID- 8525775
TI  - [Level of erythropoietin during autologous transplantation of stem cells from
      bone marrow and peripheral blood].
AB  - Using RIA method, serum erythropoietin (EPO) levels were measured in 13 patients
      undergoing autologous bone marrow transplantation (ABMT) and 4 patients with
      autologous peripheral blood stem cell transplantation (APBSCT) before and at the
      end of conditioning regiment as well as at the 3rd, 7th, 10th, 14th, 20th i 30th
      day after ABMT in correlation with actual haemoglobin (Hb) value. Statistically
      significant increase in EPO level was observed at days 0 to +14 (p < 0.01) with
      the maximum at day 3. The correlation between increased EPO level and decreased
      Hb was observed.

PMID- 8525776
TI  - [Dysfunction of the blood-brain barrier in patients with acute leukemias or
      lymphomas of high grade malignancy].
AB  - In 38 patients with acute leukemias or non-Hodgkin's lymphomas of high malignancy
      the blood-brain barrier (BBB) was prospectively analysed by means of QAlb value
      (QAlb = cerebrospinal fluid albumin/serum albumin). Cerebro-spinal fluid and
      serum were taken before each intrathecal methotrexate administration according to
      central nervous system (CNS) prophylaxis or treatment of CNS involvement by
      neoplasm. Patients were divided into two groups. Group I consisted of 5
      individuals with clinical manifestations of CNS involvement by leukemia or
      lymphoma. Group II contained 33 patients without neurological symptoms. Besides,
      group II was subdivided into other two groups: group IIa-patients with BBB
      analysis before cytostatics application, and group IIb-patients in which BBB was
      analysed after the administration of at least one cycle of protocols, used in
      general chemotherapy, including intrathecal methotrexate injection. In group I
      BBB changes were observed in 10 out of 12 assessments (sensitivity 83.3%). In
      group II BBB impairment was revealed in 11 out of 52 assessments (specificity
      78.8%). The differences in QAlb values between groups I and II were statistically
      significant (p = 0.0008), whereas there were no significant differences between
      QAlb values in groups IIa and IIb. Basing on their investigations, the authors
      conclude that neoplasm invading CNS should be considered as essential risk of BBB
      impairment, whereas intrathecal and general chemotherapy appear to be less
      important in BBB injury.

PMID- 8525777
TI  - [Influenza vaccination of children with hemophilia].
AB  - 51 haemophilic children aged from 7 to 16 years was vaccinated against influenza
      in Paediatric Department of Haematology and Oncology in November and December of
      1993. Each dose of subunit vaccine manufactured by Wyeth-USA, contained 15
      micrograms of each haemagglutinin strains as recommended for the season. The
      antibody level was studied before and after influenza vaccination in vaccinated
      and control group as well. 5-time rise of geometric mean antibody titre was found
      for H1N1 and H3N2 antigens after vaccination of the children group. Slightly
      lower, 2.7-time rise of GMT was showed for HB haemagglutinin of influenza virus.
      There was no significant rise of GMT for any among three studied virus
      haemagglutinin.

PMID- 8525778
TI  - [Non-Hodgkin's lymphoma in a patient after many years of remission of Hodgkin's
      disease].
AB  - Authors present 38-years old woman with 11-years lasting complete remission of
      Hodgkin's disease who was recognized to have non-Hodgkin's lymphoma of the base
      of the tongue and also of stomach three months later. After polychemotherapy
      complete remission was achieved.

PMID- 8525779
TI  - [Isolated infiltration of optic nerves in the course of acute lymphoblastic
      leukemia].
AB  - 51 years old male with acute lymphoblastic leukaemia in hematological remission
      was admitted to the hospital due to abrupt loss of vision. The cause of estimated
      complication was symmetrical infiltration of optical nerves. No other symptoms of
      leukaemia were observed at the time. In spite of combined radio- and chemotherapy
      no improvement was achieved. Two months later leukaemia relapse in the bone
      marrow was observed. The patient died of septic complications during reinduction
      treatment.

PMID- 8525780
TI  - Co-ordinate expression of alpha 5 beta 1 integrin and fibronectin in Dupuytren's
      disease.
AB  - The expression of alpha 5 beta 1 (alpha 5 beta 1) integrin and its extracellular
      ligand fibronectin was studied immunohistochemically in 23 cases of Dupuytren's
      disease using an immunoperoxidase method for light microscopic visualization. All
      cases consisted of multiple nodules showing a variable degree of cellularity and
      fibrosis. Depending on the histological appearance of these nodules, each case
      was assigned to the three following phases: proliferative, involutional and
      residual. Alpha 5 beta 1 integrin was detected in the highly cellular areas of
      both proliferative and involutional phases where fibronectin was simultaneously
      expressed in the extracellular matrix (ECM). Diversely alpha 5 beta 1 and
      fibronectin disappeared from the hypocellular areas of involutional phase,
      undergoing fibrotic transformation, and from the fibrotic connective tissue of
      residual phases. These findings indicate that the expression pattern of alpha 5
      beta 1 integrin correlates with the presence in the ECM of the corresponding
      ligand fibronectin during the different phases of Dupuytren's disease. We suggest
      that alpha 5 beta 1 integrin, linking fibronectin to stromal cells of both
      proliferative and involutional phases, may be involved in the contractile
      processes occurring in Dupuytren's disease.

PMID- 8525781
TI  - Existence and co-existence of vasoactive substances in nerve fibres supplying the
      abdomino-pelvic arterial tree of the female pig and cow.
AB  - The occurrence and co-localization of several presumed vasoactive neuropeptides,
      serotonin, and catecholamine-synthesising enzymes--tyrosine hydroxylase (TH),
      dopamine-beta-hydroxylase (D beta H) and phenylethanolamine-N-methyltransferase
      (PNMT)--were investigated in perivascular nerves supplying the systemic and
      distributing arteries of the abdomino-pelvic arterial tree of the female pig and
      certain arteries supplying female reproductive organs in the cow. As revealed by
      single immunofluorescence, perivascular axons immunoreactive for TH, D beta H,
      neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP),
      calcitonin gene-related peptide (CGRP) and Leu-enkephalin (LENK) occurred in both
      species examined, whereas galanin-immunoreactive (GAL-IR) nerve fibres were found
      exclusively in the pig. PNMT-, serotonin-, dynorphin A-, alpha-neoendorphin-,
      bombesin- or cholecystokinin-IR nerve terminals were not observed. The following
      classes of perivascular nerve fibres might be distinguished in the present study:
      1) noradrenergic (i.e. TH/D beta H-IR), 2) NPY-, 3) GAL- (pig only), 4) LENK-, 5)
      VIP-, 6) SP-, 7) VIP/NPY-, 8) SP/CGRP-, 9) SP/GAL- (pig only), 10) SP/VIP- (cow
      only), 11) TH/D beta H/NPY- and 12) TH/D beta H/NPY/LENK-IR. Distinct differences
      in the distribution of LENK- and SP-IR axons around particular parts of the
      studied arterial tree in individual species were also observed. The present data
      indicate that the abdomino-pelvic arterial tree of the pig and cow receive
      perivascular nerve fibres that exhibit diverse chemical codes, and that different
      chemical coding of perivascular nerve fibres in individual species may depend on
      the target organ of the particular artery.

PMID- 8525782
TI  - The appearance of active plasminogen activator of urokinase type (u-PA) in the
      rabbit anterior eye segment irradiated by UVB rays. A histochemical and
      biochemical study.
AB  - Repeated irradiation of the rabbit eye with UV rays of 312 nm wavelength (UVB)
      evoked the appearance of active plasminogen activator of urokinase type (u-PA) in
      the anterior eye segment. Using histochemistry, active u-PA appeared first in the
      corneal epithelium followed by the corneal endothelium, inflammatory cells in the
      corneal stroma and the lens epithelium. With a semiquantitative fluorescent
      method active u-PA was also found in the tear fluid and aqueous humour. UV rays
      of 365 nm wavelength (UVA) under the same conditions did not cause the appearance
      of active u-PA in the anterior eye segment.

PMID- 8525783
TI  - Influence of chronic alcohol treatment on the GFAP-immunoreactivity in astrocytes
      of the hippocampus in rats.
AB  - The influence of long term application of 5% (v/v) ethanol over a period of 36
      weeks and 10% (v/v) ethanol over a period of 4,12 and 36 weeks to Wistar rats was
      investigated. The qualitative alterations of astrocytes and quantitative changes
      of glial fibrillary acidic protein-immunoreactivity (GFAP-IR) in selected regions
      of the dorsal hippocampus were examined, using anti-GFAP and the avidin-biotin
      immunoperoxidase technique. After prolonged (36 weeks) consumption of 5% (v/v)
      ethanol insignificant alterations were observed. The administration of 10% (v/v)
      ethanol over 4 and 12 weeks led to an increase of the total GFAP-IR in the
      examined brain regions. Hypertrophy of the cell bodies and cytoplasmic processes
      were seen. After 36 weeks decreased total GFAP-IR was measured in all examined
      brain regions. Cell bodies and fibrillary processes stained less heavily, the
      number and length of the fibrillary processes decreased and the number of
      astrocytes in certain hippocampal regions (e.g. in stratum moleculare of the
      dentate gyrus) appeared reduced. The results show that exposition to ethanol led
      to the appearance of different astrocytic phenotypes, depending on the
      concentration and duration of ethanol application, on the age of animals and on
      hippocampal regions. It is suggested that GFAP can be used as a specific marker
      for ethanol-induced alterations of astrocytes.

PMID- 8525784
TI  - Immunohistochemical demonstration of tenascin in human pituitary glands and
      adenomas.
AB  - The expression of tenascin in 8 cases of normal fetal and adult human pituitary
      glands and in 51 cases of human pituitary adenomas was investigated
      immunohistochemically with the use of polyclonal antibodies against human
      tenascin. The immunohistochemical study demonstrated that tenascin is expressed
      in both fetal and adult normal epithelial cells of the anterior lobe of pituitary
      glands and in tumor cells of pituitary adenomas, which suggests that tenascin is
      synthesized by normal pituitary cells as well as by pituitary adenoma cells.
      Plurihormonal pituitary adenomas, especially those producing 4 or 5 different
      hormones, tended to show the highest incidence of positive immunoreactivity for
      tenascin, suggesting that tenascin may be involved in the aggressive behaviour of
      plurihormonal adenomas.

PMID- 8525785
TI  - Immunohistochemical demonstration of interleukin-1 beta induced changes in acute
      phase proteins and albumin in rat liver.
AB  - Interleukin-1 beta is a potent mediator of the acute-phase response. However, the
      effects of interleukin-1 beta administration on the topic in vivo production of
      acute-phase proteins and albumin are so far not well understood. Overnight fasted
      rats were subcutaneously injected with 0.2 mL 0.9% NaCl (control group) or 6.25
      micrograms recombinant human interleukin-1 beta, and rectal temperature was
      measured at intervals up to 48 h. Livers were perfused-fixed in vivo prior to
      injection (base-line), and at 9, 24, and 48 h following the interleukin-1 beta
      injection. Fibrinogen, orosomucoid (alpha 1-acid glycoprotein) and albumin were
      immunostained using a streptavidin-biotin-immunoperoxidase technique. Rectal
      temperature peaked 5 h after the single interleukin-1 beta injection, and fell
      gradually to base-line values by 24 h. Prior to injection only a few hepatocytes,
      randomly scattered throughout the liver lobule, stained positive for fibrinogen
      and orosomucoid. In contrast, all hepatocytes stained uniformly positive for
      fibrinogen and orosomucoid 9 h after interleukin-1 beta injection, whereas at 24
      h a predominant centrilobular staining pattern occurred. Due to fasting, albumin
      positive hepatocytes were already reduced at base-line in both groups.
      Interleukin-1 beta induced a further significant loss of albumin positive cells
      in the periportal zone (35 +/- 21%) at 9 h when compared with controls (58 +/-
      11%, p = 0.037). In conclusion, subcutaneous interleukin-1 beta (probably by
      stimulation of interleukin-6) strongly induces fibrinogen and orosomucoid
      expression in rat liver, and suppresses immunohistochemically stainable albumin
      in a heterogenous way, mainly in the periportal zone.

PMID- 8525786
TI  - Immunohistochemical assessment of cell proliferation in plant tissues using
      formaldehyde-fixed paraffin-embedded material.
AB  - Cell proliferation in formaldehyde-fixed and wax-embedded sections of root
      tissues from Vicia faba beans was assessed by using a monoclonal antibody raised
      against the proliferating cell nuclear antigen (PCNA). Positive PCNA
      immunoreactivity was restricted to nuclei in known proliferating zones of the
      root. The immunoreactivity of cells in metaphase/anaphase of mitosis showed
      weaker PCNA immunoreactivity while nuclei in telophase showed no PCNA
      immunoreactivity indicating that this method is well suited to label
      proliferating cells in plant tissues.

PMID- 8525787
TI  - Experimental estimation of hydrophobic parameters of tetrazolium salts.
AB  - A simple method for estimation of the hydrophobic parameters (partition
      coefficient lg P and Hansch pi-value) of tetrazolium salts is reported using
      their relative velocities in reverse-phase layer chromatography. The experimental
      test values are close to relevant calculated values of the literature.

PMID- 8525788
TI  - Immuno-analogues of erythrocyte protein 4.2 in thyroid gland.
AB  - Immuno-analogues of erythrocyte protein 4.2 were examined in rat thyroid tissues
      by immunohistochemical techniques. Immunofluorescence microscopy revealed that
      the peripheral cytoplasm below the apical plasma membrane of follicle epithelial
      cells was stained with antibodies against erythrocyte protein 4.2. The staining
      pattern was similar to that obtained with anti-ankyrin antibodies. The present
      and our recent results showing the presence of spectrin, protein 4.1 and ankyrin
      like proteins in thyroid tissues indicate that most features of the erythrocyte
      membrane skeletal architecture are also expressed by thyroid follicle epithelial
      cells.

PMID- 8525789
TI  - Immunochemical characterization and distribution of laminin in the rat tongue.
AB  - Anti-laminin serum was used to investigate the distribution and composition of
      laminin in the rat tongue. Immunohistochemical analysis showed that laminin is a
      useful marker to study the microscopic anatomy of the tongue. Laminin is
      expressed in most tissues that form this organ, such as smooth and striated
      muscle, epithelium, nerves, and endothelium, allowing the observation of fine
      details of neuromuscular junctions, taste papillae and microvasculature. Western
      blot analysis revealed that laminin extracted from the tongue differs from EHS
      tumor laminin. Tongue laminin contains B chains, while A chain seems to be
      present only in small amounts.

PMID- 8525790
TI  - Alpha-NADPH appears to be primarily oxidized by the NADPH-diaphorase activity of
      nitric oxide synthase (NOS).
AB  - Biochemical studies have shown that the NADPH-diaphorase (NADPH-d) activity of
      nitric oxide synthase (NOS) represents only a part of the total cellular
      diaphorase pool. Histochemically, NADPH-d activity can be demonstrated in cells
      expressing no constitutive NOS. Therefore, attempts aimed to improve the
      specificity of the NADPH-d reaction are currently being undertaken. In this
      study, the effect of replacing the natural and common diaphorase substrate beta
      NADPH with the artificial stereoisomer alpha-NADPH on the extent of NADPH-d
      staining was examined. When beta-NADPH served as the substrate, discrete
      populations of central and peripheral neurons as well as numerous non-neural
      cells in many organs of common laboratory rodents (mouse, rat, gerbil, hamster,
      guinea pig) and marmosets were found to generate formazan. Substitution of alpha
      NADPH for beta-NADPH resulted in reduced staining intensity of nerve cells and
      muscle fibers. Furthermore, alpha-NADPH-d staining of macula densa cells,
      enterocytes and granulocytes varied according to the species examined. No
      reaction was observed in most other cells which stained positively for beta-NADPH
      d activity. Examination of adjacent sections, incubated for the demonstration of
      NOS-immunoreactivity, revealed that alpha-NADPH-d activity and NOS immunostaining
      are strictly colocalized in neurons, striated muscle fibers and, species
      dependently, in macula densa cells. It can thus be concluded that, with the
      exception of gut granulocytes, alpha-NADPH is primarily metabolized by the
      reductase activity of NOS.

PMID- 8525791
TI  - Demonstration of nitric oxide synthase (NOS) in marmosets by NADPH diaphorase
      (NADPH-d) histochemistry and NOS immunoreactivity.
AB  - Since species interdiversity often prevents the extrapolation of laboratory
      rodent data to man and similar problems may exist for nitric oxide synthase
      (NOS), NADPH-d activity and immunohistochemistry of NOS were investigated in the
      New World monkey Callithrix jacchus (marmoset), which has been shown to be close
      to the human situation in many respects. Using the NADPHd reaction with beta
      NADPH and nitroblue tetrazolium (NBT) on acetone-chloroform pretreated
      cryosections, NBT formazan was found in many neural and non-neural (e.g. diverse
      epithelia, striated muscle fibers, vascular endothelium) cells in numerous
      tissues and organs. Prefixation with formaldehyde lowered the number of NADPH-d
      active sites and the amount of formazan with the exception of neuronal NADPH-d as
      did incubation of fresh or acetone-chloroform-pretreated sections for NADPH-d in
      the presence of 0.5% formaldehyde. When 1% formaldehyde or 0.5 mM permanganate
      were used significant amounts of formazan appeared only in central and peripheral
      neurons, vasal endothelial cells, small intestinal enterocytes, plasma membrane
      region of striated muscle fibers as well as arteriolar cells in the kidney;
      except for enterocytes, these observations were confirmed by NOS
      immunohistochemistry which revealed in addition reactive cells in the thymus and
      intestinal lamina propria.

PMID- 8525792
TI  - Ultrastructural localizations of J chains in the chicken bursa of Fabricius at
      different stages of development.
AB  - Before and after hatching, J-chain positive cells (JPC) were observed by
      immunoelectron microscopy in the chicken bursa of Fabricius. JPC were mostly
      lymphocytes, but epithelial cells were also detected as JPC. During the embryonic
      stage, J chains were mostly associated as patches with surface membranes.
      Furthermore, there was a diffuse localization in the cytoplasm. After hatching, J
      chains showed a similar subcellular localization as was seen before hatching.
      However, J chains were frequently detected in the cytoplasm, and rarely on the
      surface membranes after hatching. Staining intensities by corresponding antisera
      were stronger in the hatched chickens than in embryos. From these findings one
      may conclude that J chains are synthesized even at an early stage of B cell
      differentiation during embryonic life and are continuously produced at the later
      differentiation stages of B-cell lineage. The increased amounts of J chains
      estimated by staining intensity seem to coincide with B cell maturation and may
      correlate with signalling of IgM synthesis.

PMID- 8525793
TI  - Distribution of extracellular matrix glycoproteins in the human mesonephros.
AB  - We analyzed the expression and distribution of collagen types IV and VI, laminin
      and fibronectin during the development and regression of the mesonephros in human
      embryos and fetuses ranging from 6 to 12 weeks of gestation by indirect
      immunoperoxidase methods. Type IV collagen, laminin and fibronectin were detected
      along the glomerular, tubular and capsular basement membranes of developing and
      mature nephrons. Only type IV collagen and fibronectin were found in the
      mesangium. Type VI collagen formed a delicate interstitial fibrillar network and
      a continuous basement membrane-like structure along the mesonephric nephrons.
      Basement membranes (GBM) of developing and mature glomeruli showed a distinct
      continuous staining for this collagen. The mesangial matrix was rich in type VI
      collagen. Mesonephric involution started during the 8th week of gestation and
      coincided with a moderate expansion of mesangial matrix and progressive collapse
      of the capillary walls, while the tubules became thinner and shorter. Staining
      for all extracellular matrix glycoproteins studied showed GBM wrinkling, gradual
      disintegration of some capillary loops and glomerulosclerosis. The sclerotic
      glomeruli were strongly positive for type IV collagen and less positive for type
      VI collagen and fibronectin. Laminin was absent. Our results indicate that
      collagen types IV, VI, laminin and fibronectin may be involved in the development
      and regression of the human mesonephros.

PMID- 8525794
TI  - The anterolateral funiculus in the spinal cord in amyotrophic lateral sclerosis.
AB  - We carried out a morphometric study on the myelinated fibers in the anterolateral
      funiculus (ALF) and lateral corticospinal tract (LCS) in the cervical segment of
      the spinal cord of 13 patients with classic amyotrophic lateral sclerosis (ALS),
      6 of whom had been on a respirator; 5 age-matched subjects were used as controls.
      The results obtained revealed that: (1) the fiber-size distributions of the
      myelinated fibers in the ALF and LCS of the control subjects had peaks at 2
      microns; (2) there were marked and significant losses of large myelinated fibers
      in the ALF and LCS of ALS patients; (3) the patients who required respirator
      support showed more severe degeneration in the ALF than those who required none;
      and (4) the degree of myelinated fiber loss in the LCS did not correlate with
      either the illness duration or the history of respirator use.

PMID- 8525795
TI  - Evidence of persistent blood-brain barrier abnormalities in chronic-progressive
      multiple sclerosis.
AB  - Brain capillaries were analyzed morphometrically for alterations in organelle
      distribution and density in biopsy samples of central nervous system tissue from
      seven patients diagnosed as having chronic progressive multiple sclerosis. Data
      were expressed as percentage of endothelial cytoplasm occupied by the respective
      organelles. The density of pinocytotic vesicles in endothelium ranged from 0.53%
      within normal-appearing parenchyma to 1.2% in gliotic areas. For mitochondria the
      values ranged from 10.87% in normal areas to 4.72% in the same respective
      samples. Thus, an inverse correlation between vesicular and mitochondrial content
      was observed. These findings suggest that endothelial cells in gliotic areas are
      similar to endothelial cells of the systemic circulation in their mitochondrial
      content and pinocytotic activity. Interendothelial junctions in capillaries of
      all areas examined appeared normal. Additional evidence for a continuous blood
      brain barrier anomaly in multiple sclerosis was the accumulation of perivascular
      fibrin, suggesting an increase in microvascular permeability. Perivascular
      collagen deposits, degenerative changes in pericytes and astrocytic swelling were
      also indicators of an increase in blood-brain barrier permeability. Taken
      together with previous data from experimental autoimmune encephalomyelitis, the
      present findings in chronic silent multiple sclerosis lesions suggest that
      central nervous system endothelial cells show persistent abnormalities of the
      blood-brain barrier, even in the absence of active inflammation.

PMID- 8525796
TI  - Association of apolipoprotein epsilon 4 allele and neuropathologic findings in
      patients with dementia.
AB  - Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of
      three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the
      presence of APOE 4 is associated with an increased risk for both familial
      Alzheimer's disease and late-onset Alzheimer's disease. We extended these
      observations by determining the frequency of APOE alleles in patients with
      pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD),
      diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD
      patients without or with concomitant AD pathology and in schizophrenics with a
      progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction
      digestion of polymerase chain reaction-amplified DNA isolated from frozen brain
      samples. The frequency of the APOE epsilon 4 allele was highest among sporadic AD
      and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and
      non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE epsilon 4
      allele is over-represented selectively in patients with dementias associated with
      plaques and tangles and/or cortical Lewy bodies, but not in demented
      schizophrenics or non-demented PD patients.

PMID- 8525797
TI  - Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy.
AB  - We report the results of a clinical, electrophysiological and pathological study
      conducted in 18 AIDS patients presenting a distal symmetrical predominantly
      sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main
      complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage
      II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the
      remainder. Electrophysiological investigation confirmed the presence of an axonal
      alteration in the sensory nerves, but also revealed motor involvement in all
      cases. The neuropathological features of sensory nerves were fiber loss and
      axonal degeneration with macrophagic activation. The expression of monocyte
      macrophage markers and of major histocompatibility complex class II antigens
      appeared up-regulated in endoneurial ramified cells, while expression of CR3, a
      complement receptor involved in the process of phagocytosis, was down-regulated.
      In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we
      found HIV-related mRNA and protein located in scattered cells of the endoneurium
      which we presume to be macrophages. These data suggest that: (a) DSPN may occur
      early in the course of the disease and is not limited to later stages; (b) DSPN
      is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus
      enters the peripheral nervous system and induces changes in the immunocompetent
      cell population with activation of macrophages. Storage of the virus inside
      macrophages may act both as a reservoir for the virus and as a putative cause of
      nerve damage, probably through release of cytotoxins and/or interaction with
      trophic factors.

PMID- 8525798
TI  - Structural preservation of cerebellar granule cells following neurointoxication
      with methyl mercury: a stereological study of the rat cerebellum.
AB  - Methyl mercury intoxication causes ataxia. Structural changes of cerebellar and
      peripheral nerve tissues have been described. However, it is still unclear
      whether the ataxia is of cerebellar or peripheral origin. To clarify this
      question further, the effects of methyl mercury intoxication on the numbers of
      granule and Purkinje cells and the volume of Purkinje cell perikarya have been
      evaluated with stereological methods. Rats were intoxicated with methyl mercury,
      at a dose of 2 mg/kg per day for 19 successive days, and the analysis was carried
      out 2.5 or 4.5 weeks later. The total numbers of cerebellar granule cells and
      Purkinje cells were estimated using an optical fractionator and the mean volume
      of the Purkinje cells was estimated by the vertical rotator technique. The
      volumes of the granular cell layer, the molecular layer and the white matter were
      estimated using the Cavalieri principle. The intoxicated animals developed
      hindlimb incoordination when held by the tail. Although pronounced axonal
      degeneration occurred in the peripheral nervous system, no changes were found in
      cerebellar cell numbers or cell sizes in either of the test groups. The absence
      of detectable light microscopic changes in the cerebellum indicates that the
      peripheral nervous system is affected prior to the cerebellum in rats intoxicated
      with organic mercury.

PMID- 8525799
TI  - Apolipoprotein E genotype and neuropathological phenotype in two members of a
      German family with chromosome 14-linked early onset Alzheimer's disease.
AB  - Molecular genetic analysis was performed in two autopsy-confirmed cases of early
      onset Alzheimer's disease belonging to a large German pedigree [FAD2, according
      to the nomenclature of St. George-Hyslop, et al. (1987) Science 235:885-890]. The
      disease in this family has been linked to chromosome 14. As gene interactions are
      considered to influence the age of onset and tissue pathology in Alzheimer's
      disease, we have studied three candidate genes that could modify disease
      progression. In this study a new polymerase chain reaction (PCR) assay was
      established for apolipoprotein E genotyping in archival neuropathological tissue,
      exon 17 of the amyloid precursor protein gene was directly sequenced, and a
      candidate mutation site at nucleotide (nt) 5460 of the mitochondrial NADH
      dehydrogenase subunit gene ND2 was analyzed employing PCR followed by HphI
      digestion. Whereas no sequence variations were detected in exon 17APP or at
      nt5460 of mitochondrial DNA, the apolipoprotein E genotypes of the two cases
      differed. Neuropathological examination revealed a higher number of beta A4
      positive amyloid plaques and a larger total tissue area covered by beta A4
      deposits in the epsilon 3/epsilon 3 homozygote. In contrast, the number of
      cortical neurofibrillary tangles and the number of plaques with tau-positive
      neurites appeared to be higher in the epsilon 3/epsilon 4 heterozygote. Our
      findings support the view that the chromosome 14 genetic defect, rather than
      apolipoprotein E genotype, is the preeminent factor determining Alzheimer's
      disease pathology in this family.

PMID- 8525800
TI  - Endothelial lipopigment as an indicator of alpha-tocopherol deficiency in two
      equine neurodegenerative diseases.
AB  - Two spontaneous neurodegenerative diseases of the horse, equine motor neuron
      disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been
      associated with alpha-tocopherol deficiency, and both were characterized by
      prominent accumulations of endothelial lipopigment in the small vessels of the
      spinal cord. These endothelial pigment deposits appear to be reversible. In EMND
      horses pasture-supplemented for 9 months or more after the progression of
      weakness and wasting had arrested, there was very little endothelial lipopigment.
      The origin and the potential effects of these endothelial lipopigment
      accumulations are discussed.

PMID- 8525801
TI  - Hepatic retinopathy: morphological features of retinal glial (Muller) cells
      accompanying hepatic failure.
AB  - More than 80 years ago, Alzheimer described changes in the brains of patients who
      had suffered hepatic failure. Astrocytes are primarily affected; their nuclei
      become swollen, their intermediate filament protein composition is altered and
      their cytoplasm becomes vacuolated. Cells with these features are called
      Alzheimer type II astrocytes and these changes have been attributed to the toxic
      effects of elevated ammonia levels. The present study investigates whether the
      dominant glia of another part of the central nervous system, the Muller cells of
      the retina, undergo similar changes. Retinae of patients who had died with
      symptoms of hepatic failure were processed for histology, histochemistry, and
      immunocytochemistry. Cell nuclei were measured from brain astrocytes (insula
      cortex), Muller cells, and retinal bipolar neurons. Hepatic failure resulted in
      the enlargement of nuclei in astrocytes and Muller cells, and the enhanced
      expression in Muller cells of glial fibrillary acidic protein, cathepsin D, and
      the beta-subunit of prolyl 4-hydroxylase (glial-p55). In some retinae, signs of
      gliosis were also observed. We conclude that increased levels of serum ammonia
      resulting from hepatic insufficiency cause changes in Muller cells that are
      similar to those seen in brain astrocytes. We term this condition hepatic
      retinopathy.

PMID- 8525802
TI  - Oxidized cellulose causes focal neuropathy, possibly by a diffusible chemical
      mechanism.
AB  - We observed incidentally that rat sciatic nerve in contact with oxidized
      cellulose (OC), an absorbable hemostatic agent, underwent focal fiber
      degeneration, and we undertook studies to determine the mechanism of its
      production. Topically applied OC generated acute nerve damage within the adjacent
      nerve fascicle of rat sciatic nerve in a dose-dependent fashion (r = 0.99, P <
      0.01, threshold amount: 9.9 mg). IN single teased fibers, the predominant type of
      myelinated fiber damage was axonal degeneration. The subperineurial blood flow of
      the rat sciatic nerve was serially measured by microelectrode hydrogen
      polarography, and the reduction at 90 min after application of OC was not greater
      than that of controls. A thin polyethylene membrane interposed between OC and the
      sciatic nerve almost completely prevented the nerve damage. These data suggest
      that the chief mechanism of nerve damage by OC was neither compression nor
      ischemia, but was a diffusible chemical mechanism. Care should be taken to avoid
      direct OC application around peripheral nerves.

PMID- 8525803
TI  - Relationship of amyloid beta/A4 protein to the neurofibrillary tangles in
      Guamanian parkinsonism-dementia.
AB  - The Chamorro population of the island of Guam is highly susceptible to a disease
      called lytico-bodig (LB), which clinically resembles a mixture of amyotrophic
      lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer disease (AD). The
      disease is characterized by the widespread development of neurofibrillary tangles
      in the central nervous system. These tangles have an immunohistochemical profile
      indistinguishable from that seen in AD. We studied by immunohistochemistry the
      occurrence of intracellular and extracellular neurofibrillary tangles in LB in
      the entorhinal cortex, hippocampus and substantia nigra using antibodies to tau
      protein and ubiquitin. We also studied the relationship of these tangles to
      amyloid precursor protein (APP) and its beta-amyloid fragment (BAP), using
      multiple antibodies to BAP and other APP sequences. In advanced cases of LB, the
      development of neurofibrillary tangles was far more severe than in advanced cases
      of AD. Virtually all neurons of CA-1 and the subiculum were lost and only ghost
      tangles remained. In areas dominated by such extracellular tangles, BAP deposits
      were frequently observed developing around the fibers of ghost tangles. In some
      cases, the deposits covered only a few of the fibers, but in others, they seemed
      to envelope the complete tangle. The deposits were thioflavin S and Congo red
      positive, indicating that the BAP was in a consolidated form. We describe these
      entities as "tangle-associated amyloid deposits". Such BAP deposits have
      previously been described in some cases of AD, dementia pugilistica and LB.
      However, we found them in all cases of LB with dementia in the hippocampal
      entorhinal areas and in most cases in the substantia nigra. They do not evolve
      from diffuse BAP deposits since they are remote from them, and they do not trap
      dystrophic neurites. The fact that extracellular tangle material can act as a
      nidus for BAP build-up in LB suggests that further consideration needs to be
      given to the ways in which extracellular BAP deposits are formed.

PMID- 8525804
TI  - Muscle regeneration and mitochondrial calmitine increase in the dystrophic dy/dy
      mouse after intramuscular chlorpromazine injection.
AB  - We studied the effect of chlorpromazine injection on the gastrocnemius muscles of
      C57BL/6J dy/dy dystrophic mice. Changes in mitochondrial calmitine concentrations
      and differences in microscopy studies, fibre typing and morphometry were compared
      in gastrocnemius muscles of dystrophic and control mice before and 2 and 21 days
      after injection. In both cases, calmitine reduction associated with muscle
      degeneration was observed 2 days after drug injection. Calmitine then increased,
      reaching a level at day 21 nearly identical to that of controls before injection.
      This increase was associated with muscle regeneration. These results clearly
      indicate that dystrophic mouse muscle can regenerate calmitine after drug-induced
      damage.

PMID- 8525805
TI  - Distribution and analysis of surface charge on brain endothelium in vitro and in
      situ.
AB  - Vascular endothelial cells are associated with a number of anionic molecules.
      These anions are important in endothelial function, particularly in regulating
      permeability, haemostasis and cellular traffic. To explore the nature and
      distribution of anions on the brain endothelial cell (BEC) surface, we have
      examined rat brain endothelium in culture, and in situ. The anionic sites were
      probed with cationic colloidal gold and cationised ferritin, and visualised by
      light microscopy. Additionally we compared the distribution of the anionic sites
      on BEC with that present on other endothelial cell types in culture. The
      predominant anion detected on BEC was heparan sulphate (HS). This was distributed
      throughout the cell membrane, but was most densely associated with intercellular
      junctions. This pattern was distinct from the anionic locations observed in
      endothelia from aorta and epididymal fat microvessels. The distribution of anions
      was dependent on the age of cultured cells, with only minimal levels of HS seen
      at the periphery of younger cells. The nature and distribution of negative charge
      was different in situ. Here, sialic acid was the major surface anion, with only a
      small contribution from HS. The significance of these findings are discussed in
      relation to endothelial function in normal tissue and in pathological conditions.

PMID- 8525806
TI  - Restricted infection with canine distemper virus leads to down-regulation of
      myelin gene transcription in cultured oligodendrocytes.
AB  - Canine distemper virus (CDV) induces oligodendroglial degeneration and multifocal
      demyelination in the central nervous system. The mechanism of oligodendrocyte
      degeneration is not understood but it has been shown that there is a restricted
      infection of these cells without viral protein production. Using a combination of
      immunocytochemistry and in situ hybridization we were able to demonstrate the
      transcription of the entire virus genome throughout the whole observation period
      (7-35 days after infection) in oligodendrocytes in CDV-infected brain cell
      cultures. Therefore, the lack of viral protein and particle production can not be
      explained on the basis of a defective viral transcription. The present study also
      shows that a restricted infection of oligodendrocytes with CDV down-regulates the
      transcription of the major myelin genes coding for proteolipid protein, myelin
      basic protein (MBP) and myelin-associated glycoprotein in a very similar way.
      Using densitometry for in situ hybridization products of MBP in populations of
      normal and infected oligodendrocytes, an effect could be observed long before
      morphological changes were detectable. The present results strongly suggest that
      demyelination in distemper is induced by a restricted CDV infection of
      oligodendrocytes which down-regulates the expression of a variety of cellular
      genes, in particular those coding for myelin proteins. Consequently, the infected
      cells are no longer able to synthesize all the membrane compounds which are
      necessary for maintaining their structural integrity.

PMID- 8525807
TI  - Dysembryoplastic neuroepithelial tumors in two children with neurofibromatosis
      type 1.
AB  - Dysembryoplastic neuroepithelial tumors (DNT) occur mainly in children and are
      always clinically associated with intractable complex partial seizures. In the
      first report, which included 39 cases, the patients had no neurological deficit
      and no stigmata of phacomatosis. In contrast, we observed a DNT in 2 children
      with a neurofibromatosis type 1. The first patient developed intractable complex
      partial seizures at age 9 years and was operated at the age of 13 years.
      Neuroimaging study showed multifocal involvement with three separated lesions in
      the frontal, parietal and temporal lobes. The second patient was a 16-year-old
      boy with 5-year history of severe and refractory epilepsy. Magnetic resonance
      imaging identified a right temporal lesion and the patient underwent a right
      temporal lobectomy. This unusual association of two cases of DNT with
      neurofibromatosis type 1 raises the question of whether this association is
      specific or fortuitous.

PMID- 8525808
TI  - In situ polymerase chain reaction detection of HTLV-I provirus and expression of
      the p53 tumor suppressor gene in infiltrating cells in skeletal muscle from a
      patient with adult T cell leukemia.
AB  - We report the pathological changes in skeletal muscle from a patient with acute
      adult T cell leukemia (ATL). HTLV-I provirus was detected in infiltrating cells
      using in situ polymerase chain reaction in frozen sections. Furthermore, aberrant
      expression of the p53 protein was observed in the infiltrating cells. As p53
      protein was not observed in mononuclear inflammatory cells in patients with
      polymyositis, expression of the p53 protein was considered to be one of the
      characteristic findings in ATL cells. This is the first direct detection of ATL
      cells in skeletal muscle.

PMID- 8525809
TI  - Tissue distribution and disease manifestations of the tRNA(Lys) A-->G(8344)
      mitochondrial DNA mutation in a case of myoclonus epilepsy and ragged red fibres.
AB  - This man with myoclonus epilepsy and ragged red fibres (MERRF) syndrome due to
      the tRNA(Lys) A-->G(8344) mutation of mitochondrial DNA (mtDNA) died of
      bronchopneumonia at 18 years of age. He had progressive clinical symptoms from 6
      months of age manifesting as ataxia, myoclonic seizures, and muscle weakness. A
      post-mortem examination revealed 91-99% mutated mtDNA in all 32 examined tissue
      samples, including various organs and different brain regions. The brain appeared
      without macroscopic changes, but microscopic examination showed degeneration with
      loss of nerve cells and gliosis affecting the globus pallidus, substantia nigra,
      red nucleus, dentate nucleus, inferior olivary nucleus, cerebellar cortex, and
      the spinal cord. Skeletal muscle showed cytochrome c oxidase deficient muscle
      fibres with proliferation of mitochondria. In addition to pathological changes of
      muscle and brain there were few morphological changes that could be attributed to
      his mitochondrial disease. These data support the concept that in patients with
      the tRNA(Lys) A-->G(8344) mutation who are manifesting disease there are high
      levels of mutated mtDNA in all tissues, but only some tissues and brain regions
      are vulnerable.

PMID- 8525810
TI  - A histochemical and electron microscopic study of skeletal and cardiac muscle
      from a Fabry disease patient and carrier.
AB  - Histochemical and electron microscopic studies were performed in an attempt to
      clarify the muscle pathology in an 18-year-old man with Fabry disease, showing
      proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier
      with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes
      revealed by histochemistry, electron microscopy demonstrated the widespread
      accumulation of abundant lamellated bodies in myofibers, associated with
      increased glycogen granules and autophagic vacuoles. The cardiac muscle of the
      proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic
      myofibers containing a number of ring-like, lamellated bodies. Although further
      studies are necessary to support our findings, skeletal muscle is apparently
      involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle
      involvement possibly reflecting Lyonization, may be one of the characteristic
      findings of a Fabry disease carrier.

PMID- 8525811
TI  - [Patellar subluxation: where are we in 1995?].
AB  - In 1995 orthopedic surgeons cope daily with problems related to patellofemoral
      pathology. The lack of a true relation between the anomalies and the clinical
      signs is only one of the misleading factors. In spite of the abundant literature
      on the subject, misunderstanding remains the rule, starting with lack of
      consensus about the value of words and what they mean. Solutions will come only
      from a rigorous and scientific approach, in which imaging techniques will
      probably play a major role. This will be the only way to get rid of one of the
      last important myths of knee pathology: "the patellar pain syndrome".

PMID- 8525812
TI  - Electrical stimulation of bone nonunion with the presence of a gap.
AB  - A total of 22 established nonunions was treated with a capacitively-coupled
      electrical signal. A gap of 0.5 cm or more between the fragments was present in
      all of these nonunions. After an average of 26 weeks of treatment with capacitive
      coupling, radiographic assessment showed solid bone union in 72.7% of the cases.
      The results were better when the fracture site was metaphyseal. When the site was
      diaphyseal, bone healing was mainly achieved by bone trabeculae invading the gap.
      When the site was metaphyseal, healing occurred by the formation of a peripheral
      callus. The results were not affected by the presence of infection. In 8 of the
      cases osteomyelitis occurred, but all healed.

PMID- 8525813
TI  - Value of clinical provocative tests in carpal tunnel syndrome.
AB  - The value of five provocative tests for the diagnosis of carpal tunnel syndrome
      (CTS) was assessed in four groups: 54 hands with confirmed CTS, 12 with typical
      symptoms but normal electrophysiological studies, 16 hands in persons with
      diabetes and 81 hands in normal controls. Compared to normal controls the Tinel
      sign and the closed first test are highly specific; Durkan's compression test is
      not useful to discriminate between symptomatic patients with and without EMG
      disturbances. The closed fist test is specific in these situations.

PMID- 8525814
TI  - [Carpal tunnel syndrome in patients on hemodialysis (apropos of 17 cases)].
AB  - This work is based on a series of 12 patients on hemodialysis who were operated
      on for a carpal tunnel syndrome, 66% of whom were seen with an average follow-up
      of 39 months (range 4 to 99 months). The operation was performed bilaterally on 5
      occasions, which brings the number of hands operated to 17. Of the hemodialyzed
      patients 9.2% presented with median nerve compression. The main etiologies of
      renal insufficiency were chronic, interstitial nephropathies (5 cases) and
      chronic glomerular nephropathies (5 cases). All the patients were operated
      without a pneumatic tourniquet in order to preserve arteriovenous fistula
      permeability. In addition to division of the flexor retinaculum, 3 approaches to
      the Guyon canal, 3 anterior epineural membrane removals and 8 partial
      synovectomies of the flexors were performed. The postoperative evaluation
      included bilateral clinical and electromyographic analysis of both hands. In this
      study, the authors indicate the preferential appearance of certain sequelae
      specific to this type of syndrome for the hemodialyzed patient, and they propose
      therapies which could reduce their incidence. The use of electromyograms for
      systematic screening must be considered within the scope of earlier performance
      of surgery, this would help avoid irreversible neurological lesions.

PMID- 8525815
TI  - Influence of the running shoe sole on the pressure in the anterior tibial
      compartment.
AB  - The objective of the study was to evaluate the influence of a negative shoe sole
      on the intracompartmental pressure in the anterior tibial compartment. In 35
      volunteers, the compartment pressure was documented during a 20-min. run on a
      treadmill with conventional running shoes and with running shoes with a negative
      sole. Besides the documentation of the compartment pressure we also performed a
      gait analysis. The comparison of gait cycle between the conventional shoe and the
      shoe with a negative sole showed remarkable differences. With the conventional
      shoe, plantar flexion after initial contact was 16 degrees compared to 6 degrees
      with the special shoe. Duration of plantar flexion with the normal shoe was 0.17
      sec. compared to 0.1 sec. with the special shoe. The intraindividual comparison
      of the individual pressure curves revealed evident differences in most of the
      subjects. The comparison of maximum pressures of each volunteer after running
      with the normal shoe as well as with the special shoe showed a decrease in the
      maximum pressure level when using the special shoe. The maximum pressures with
      the normal shoe (59.7 +/- 9.1 mm Hg) were significantly higher than with the
      special shoe (36.5 +/- 11.8 mm Hg) (p < 0.001). The comparison of the mean
      pressure showed similar results. With the normal shoe a mean pressure of 47.1 mm
      Hg (+/- 9.0 mm Hg) was measured compared to 29.8 mm Hg (+/- 11.0 mm Hg) with the
      special shoe (p < 0.001). Regarding the subjective comfort of the special shoe 18
      subjects did not find any difference in comparison with the normal shoe.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8525816
TI  - Aneurysmal bone cyst. Long-term results and functional evaluation.
AB  - A study was performed on 13 patients with 16 primary aneurysmal bone cysts (ABC)
      to assess long-term results and functional outcome. The average age at diagnosis
      was 19.8 years. The anatomical sites were femur (4), tibia (5), humerus (2),
      fibula (2) and other (3). Four ABC's required no treatment. One patient underwent
      radiotherapy for an ABC of the spine. Eleven ABC's were treated surgically,
      mostly by intracapsular resection and bone grafting. Three patients had a total
      of 6 recurrences, which needed further treatment. At the time of follow-up
      (average period: 102 months), the average functional evaluation rate of 13
      patients was 96%. These functional results were graded as excellent in 9 patients
      and good in 4.

PMID- 8525817
TI  - Prevention of heterotopic ossification with tenoxicam following total hip
      arthroplasty: a double-blind, placebo-controlled dose-finding study.
AB  - The effect of tenoxicam 10 mg and 20 mg, administered daily for 6 weeks to
      prevent heterotopic bone formation after total hip arthroplasty, was evaluated in
      a randomized, double-blind, placebo-controlled trial involving 90 patients. After
      3 months, patients who had received the active drug, including those who had
      received only half the recommended anti-inflammatory dosage, had significantly
      less heterotopic bone formation. After 6 months the difference between treatment
      groups and placebo became smaller but remained significant. Adverse reactions
      occurred in only 3 patients, reflecting no differences between the groups. The
      study results, including radiographic, clinical and biochemical evaluations,
      demonstrate that treatment with tenoxicam 20 mg daily and even with tenoxicam 10
      mg daily for 6 weeks, starting immediately after total hip arthroplasty, is
      effective in preventing ectopic bone formation.

PMID- 8525818
TI  - Long-term results of radial shortening for Kienbock's disease.
AB  - The long-term evaluation (mean 4.5 years) of radial shortening in 17 patients
      with Kienbock's disease demonstrated an improvement in pain, but no patients are
      painfree, and mobility and force are restricted respectively to 69.5% and 72% of
      the contralateral side. Radiographically, further evolution of the lunatomalacia
      could not be prevented. The possibility of creating distal radioulnar joint
      dysfunction and/or ulnar impaction requires in our view a reconsideration of
      these leveling techniques in the treatment of Kienbock's disease.

PMID- 8525819
TI  - In vitro opto-electronic analysis of 3-D segmental vertebral movements during
      gradual rib lengthening in the pig.
AB  - The effects of gradual rib elongation on the 3-D position of neighboring
      vertebrae were studied in vitro in two pig specimens. The ends of one
      osteotomized rib were gradually distracted and the micromovements of the
      numerically corresponding vertebra with the osteotomized rib were studied in
      relation to the subjacent and suprajacent vertebrae with an opto-electronic
      motion analysis device. The study showed that gradual lengthening of the rib
      resulted in micromovements of the central vertebra in relation to the neighboring
      vertebrae registered as a) lateral translation in the coronal plane, b) rotation
      in the horizontal plane (both a and b were movements towards the opposite side of
      the lengthened rib), c) ventral translation in the sagittal plane and d) tilt in
      the coronal and sagittal planes. All movements were registered simultaneously.
      There was a significant linear correlation with the degree of rib elongation.
      From the results of this study it is concluded that gradual elongation of one rib
      affects the position of the numerically corresponding vertebra in relation to the
      suprajacent and subjacent vertebrae in the three cardinal planes in the same way
      as the apex vertebra is affected in idiopathic scoliosis. Moreover, the
      registered tilt, i.e., the rotational movement of the central vertebra in the
      coronal plane, could explain the wedging of the disc space, and the ventral
      translation in combination with the tilt in the sagittal plane could account for
      the lordotic tendency of the scoliotic segment.

PMID- 8525820
TI  - Factors influencing neurological recovery in burst thoracolumbar fractures.
AB  - The association between the thoracolumbar vertebrae fracture pattern, treatment
      and neurological recovery was estimated. Sixty-three patients with burst
      fractures at the T11 to L2 vertebral level and associated neurological deficit
      were evaluated by plain roentgenograms, CT scan and a quantitative neurological
      examination. The parameters used were percent canal compromise, location of the
      retropulsed middle column fragment, kyphosis, type of treatment, and neurological
      recovery. The follow-up varied from 24 to 84 months (mean 44 months). Treatment
      was conservative in 15 patients and surgical in 48 patients. Posterolateral
      decompression was carried out in 26 patients. The severity of the initial
      paralysis did not correlate with the initial fracture pattern except perhaps for
      Frankel A cases. Neurological recovery did correlate with the initial kyphosis
      but not with the amount of canal compromise or the location of the middle column
      fragment. Neurological recovery did not correlate with decompression. Improvement
      of paralysis was associated with restoration of the sagittal spine alignment.
      From the patients with greater than 5 degrees correction of kyphosis the majority
      improved neurologically. If the correction of the kyphosis was less than 5
      degrees the recovery was poor regardless of the method used. We assume that the
      initial paralysis in burst fractures with severe kyphosis is partially caused by
      permanent cord or root damage and partially by neuroapraxia from angulation of
      the neural structures and their vessels. With reduction of the fracture and
      correction of the kyphotic deformity, spinal cord, roots and their vessels become
      lax, and the chances for neurological recovery increase significantly.

PMID- 8525821
TI  - Late presentation of bilateral habitual dislocation of the patella on flexion.
AB  - We describe the case of a 56-year-old woman who, despite having bilateral
      habitual dislocation of the patella, remained asymptomatic until an injury to her
      left knee. We suggest that there is a need for a randomized study to evaluate the
      results of surgical and nonsurgical treatment.

PMID- 8525822
TI  - [Bipolar dislocation of the first metatarsal bone].
AB  - Simultaneous dislocation of the first cuneometatarsal joint and
      metatarsophalangeal joint is a rare injury. The case of a 22-year-old man is
      reported, but no previous cases have been reported in the literature. The
      treatment by closed reduction and pinning was very classical. Occasionally the
      reducibility of the metatarsophalangeal joint may be made more difficult by the
      interposition of a sesamoid bone. The simultaneous dislocation occurred because
      the injury was very severe. After 2 years, the function and mobility of the toe
      were normal, but radiographs revealed modifications of the Lisfranc joint.

PMID- 8525823
TI  - Secondary forearm deformity due to injury to the distal ulnar physis.
AB  - We present a case of deformity of the forearm with painful functional limitation,
      after a fracture of the distal third of the radius associated with a nonapparent
      lesion of the distal physis of the ulna, Salter-Harris type V, suffered by a
      patient 6 years earlier. This fracture caused premature growth arrest in the
      bone. It was treated with a plane-oblique corrective osteotomy in the radius
      together with distal radio-ulnar arthrodesis, following the Sauve-Kapandji
      technique, with excellent cosmetic and functional results.

PMID- 8525824
TI  - Ulnar nerve compression in Guyon's canal caused by a pseudotumor of the pisiform.
AB  - A rare case of ulnar nerve compression at the wrist by a hypertrophic pisiform is
      reported. The patient was treated with pisiform bone excision, and this resulted
      in complete relief of symptoms with no functional deficit.

PMID- 8525825
TI  - Bilateral posterior four-part fracture-dislocation of the shoulder.
AB  - A case of a bilateral posterior four-part fracture dislocation of the shoulder
      after a convulsive seizure was treated conservatively on one side, while the
      other shoulder was replaced by a hemiarthroplasty. A review of the literature and
      a treatment protocol for managing these injuries are presented. In four-part
      fracture-dislocations good results can be achieved with conservative treatment,
      but when avascular necrosis is likely to occur (delay in diagnosis or dubious
      relationship of the fragments after reduction) it is better to replace the
      humeral head.

PMID- 8525826
TI  - Laryngotracheal anatomy and physiology.
AB  - Thorough knowledge of the laryngotracheal anatomy and physiology is a
      prerequisite for understanding the pathophysiology and for an adequate treatment
      of patients with anomalies, stenoses and other pathology in this area. The larynx
      is part of the upper respiratory tract, our voice organ and it prevents the
      passage of secretion and food to the lower airways. Anatomical differences
      between adults and children, males and females are important to consider, as the
      size of the structures underlies the decision for the size of tubes and cannulas
      to be used. Knowledge of the muscles and mucosa is important in augmentation,
      e.g. in phono-surgery and for procedures in patients with laryngeal palsy. The
      trachea with its location causes specific problems in the treatment of stenoses
      and tumours. The mucociliary system is nowadays being more focused upon.

PMID- 8525827
TI  - Management of infant laryngeal disorders in relation to wound healing processes
      of the rabbit larynx.
AB  - Laryngotracheal injury caused by prolonged intubation is mostly treated by
      reintubation or surgical intervention. To understand the histopathological
      processes involved in wound healing of laryngeal trauma and to assess the value
      of reintubation as treatment for post-intubation injury, the findings of a study
      in preterm infants were placed next to the results of experimental studies on
      laryngeal disorders in young, growing rabbits. Observations at
      laryngobronchoscopy in the child are compared to histopathological investigations
      in the animal. In both series various, evidently similar categories of injury
      could be distinguished viz. edema, ulcerations and granulations. The results of
      treatment like reintubation would vary with the diagnosed category of the injury;
      the more granulation tissue, the less successful conservative treatment will be.
      It is concluded that histopathologic classification is essential for good
      management of intubation injuries and that therapeutic re-intubation in case of
      superficial lesions should precede the decision for surgery.

PMID- 8525828
TI  - Pathophysiology of laryngotracheal stenosis. Some important anatomical
      dimensions.
AB  - Three principal effects, increased resistance to air flow, blockage of
      mucociliary transport mechanism and impaired voice quality are discussed.

PMID- 8525829
TI  - Imaging of laryngeal and tracheal stenosis.
AB  - Most laryngeal and tracheal disorders will sooner or later narrow the airway
      lumen to some degree. Often a presumptive diagnosis may be considered from an
      evaluation of the history and symptoms. A final diagnosis is often possible by
      visual inspection through laryngoscopy and tracheo-bronchoscopy, but in the case
      of submucosal or extrinsic pathology only narrowing of the airway is detected;
      radiography can be of great value in coming to a definitive diagnosis. After a
      brief discussion of the normal anatomy of the larynx and cervical trachea, this
      manuscript reviews the imaging features of several pathological entities causing
      stenosis of these structures, without being exhaustive. Many radiological
      procedures of varying complexity have been devised to study these organs;
      emphasis will be placed on computer tomography (CT) and to a lesser extent on
      magnetic resonance imaging (MRI), as these imaging modalities usually provide
      most information.

PMID- 8525830
TI  - Correlation between functional, radiological and anatomical abnormalities in
      upper airway obstruction (UAO) due to tracheal stenosis.
AB  - Few data are available on the relative sensitivity of different lung function
      tests in upper airway obstruction (UAO) and on the correlation of these tests
      with radiological estimations of tracheal stenosis. This paper is based on
      patients with a goiter or tracheal tumor and in healthy subjects breathing
      through rigid resistors, as well as on literature data. Lung function
      abnormalities present a specific pattern in UAO: this is characterised by a
      typical shape of the maximal flow-volume curve, a marked reduction in peakflow
      (PEF) and only minor changes in routine spirometry (e.g. FEV1, which thus tends
      to underestimate the stenosis). The clinical relevance of the lung function
      abnormalities in UAO can be estimated from their relationship with the exercise
      limitation: a moderate exercise limitation to about 60% pred is found if PEF is
      reduced to about 40% pred, and Raw is increased to about 600% pred (in which
      instance FEV1 is still 75% pred). This limitation grossly corresponds to a UAO of
      about 6 mm diameter. No good correlation is found between lung function
      abnormalities and the radiological stenosis (CT-scan or X-ray): CT-scan or X-ray
      are only moderately correlated with each other. Moreover, stenosis can be
      visualised through X-ray in only about 60% of the cases.

PMID- 8525831
TI  - Prevention of postintubation laryngotracheal stenosis.
AB  - Laryngotracheal complications after translaryngeal intubation and specifically
      tracheotomy are a common problem. Surgical correction of PITS is not always
      successful. Pathogenetic mechanisms of PITS are direct pressure necrosis by
      overinflated endotracheal tube and cuff material, duration of intubation, macro-
      and microtrauma during intubation, the specific technique of endotracheal
      intubation, severity of respiratory failure, infection and poor tissue perfusion
      due to hemodynamic instability. Following preventive guidelines are proposed: the
      use of high volume low pressure cuffs, cuff pressure monitoring, ventilatory
      support with lower airway pressures, prevention of macrotrauma during intubation
      and microtrauma during maintenance, adapted policy of choice between
      translaryngeal and tracheotomy techniques, anti-infectious strategy and swift
      hemodynamic stabilization.

PMID- 8525832
TI  - Management of acute laryngeal trauma.
AB  - Accurate assessment of the extent of an acute laryngotracheal injury has
      permitted treatment ranging from observation to open reduction. The keystones for
      successful treatment of acute laryngeal trauma and hence for prevention of
      laryngeal stenosis are: Accurate evaluation of the larynx using laryngoscopy and
      CT scanning. Immediate airway management to provide a safe airway. Repair of
      displaced laryngeal fractures and mucosal lacerations with the placement of a
      soft silicone stent in the severe cases.

PMID- 8525833
TI  - CO2 laser and Gianturco stent for endoscopic treatment of tracheal stenosis.
AB  - The self-expandable Gianturco stent was used in eleven cases of tracheal stenosis
      treated from September 92 to July 94. The stent is placed through a 9 mm outside
      diameter bronchoscope under optical control after cross-section and dilation of
      the stenosis with the CO2 laser according to the Shapshay technique. The follow
      up varies from 3 to 22 months with a mean of 12 +/- 6 months. Pulmonary function
      tests (PFTs) show a mean improvement of the PEF (peak expiratory flow).
      Complications have been corrected in three patients with a second endoscopic
      procedure: the first case for malposition, the second for granuloma at the
      superior end of the prosthesis, and the third for the development of a mucous
      membrane webbing between the two loops of the stent. Owing to the lack of long
      term follow-up, we reserve this technique for the treatment of severe tracheal
      stenosis with cartilage impairment in patients contraindicated when external
      reconstructive surgery is contraindicated.

PMID- 8525834
TI  - Possibilities and indications for Nd-YAG laser and dilation therapy in the
      management of tracheal stenosis.
AB  - The possibilities for therapeutic bronchoscopy have rapidly expanded during the
      last decade. Several techniques can be used exclusively or complementary to each
      other: dilation therapy, Nd-YAG laser photoresection and endobronchial stent
      insertion. This armamentarium can be used in several forms of tracheal stenosis,
      both benign and malignant. In post-intubation injuries and other benign
      conditions it can be a definitive treatment. In neoplastic tracheal stenoses,
      these procedures allow the time needed for proper staging and sometimes surgical
      resection, or very valuable palliation in well selected patients with inoperable
      disease.

PMID- 8525835
TI  - Paediatric laryngotracheal reconstruction: 20 years' experience.
AB  - Since 1974, nearly 800 open pediatric airway reconstruction procedures have been
      performed. Data on these procedures and patients are being systematically
      recorded as part of an airway procedures database. When complete, the database
      will facilitate the tracking and description of reconstructive techniques and
      their success as they evolve. This preliminary look at twenty years' experience
      with paediatric airway reconstruction is an overview of the changes that have
      occurred in the etiology of airway stenosis and the surgical procedures used to
      correct it.

PMID- 8525836
TI  - Cricotracheal resection for pediatric subglottic stenosis: update of the Lausanne
      experience.
AB  - Controversy still exists concerning the best treatment modality for severe
      (Cotton's grade III and IV) subglottic stenosis in infants and children. Although
      laryngotracheoplasty procedures remain the operation of choice in most centres,
      this series of 26 partial cricoid resections with primary thyrotracheal
      anastomoses show a decannulation rate of 96% (25/26 cases) after a single open
      procedure. Twenty-three patients practice sport freely without dyspnea, 2 show a
      slight exertional stridor and one teenager experienced a complete restenosis. The
      postoperative voice is normal in 18 (70%) and a slight residual dysphonia is
      present in 7 (27%). We encountered no lesion to the recurrent laryngeal nerves
      and no fatalities. In 10 cases, the tracheostoma site was resected during the
      same operative session. In the future, cricotracheal resection should be
      considered as an important, if not the best, treatment option for severe
      subglottic stenosis in infants and children.

PMID- 8525837
TI  - Management of tracheal stenosis in children.
AB  - OBJECTIVE: Review presentation and outcome in pediatric patients identified
      either because of complete tracheal ring malformation or those undergoing
      tracheal resection or partial cricoid resection with primary tracheal
      anastomosis. DESIGN: Retrospective chart analysis in an academic tertiary
      referral pediatric hospital in the United States. PARTICIPANTS: Twenty-three
      children undergoing surgical repair of complete tracheal ring malformation from
      1985 to 1995. Sixteen children with tracheal stenosis undergoing resection from
      1984 to 1995. RESULTS: In patients with complete tracheal rings the mortality
      rate is 39% (9/23) with 47% (11/23) now extubated. The recent mortality rate is
      25% (2/8) with 62% (5/8) now extubated. Sixteen patients underwent tracheal
      resection or cricotracheal resection. Twelve patients had tracheal resection with
      primary tracheal anastomosis. Eleven of these are now decannulated (92%). Four
      patients underwent partial cricoid resection with primary thyrotracheal
      anastomosis. All of these patients are decannulated without need for further
      surgery (100%).

PMID- 8525838
TI  - Subglottic resection with primary tracheal anastomosis including synchronous
      laryngotracheal reconstruction.
AB  - Etiology, clinical presentation and management as found in the literature of
      subglottic stenosis are received. Personal experience and results are reported.

PMID- 8525839
TI  - Augmentation techniques in laryngotracheal reconstruction.
AB  - The treatment of laryngotracheal stenosis remains challenging. Even with the wide
      variety of current techniques available, optimal reconstruction is not possible
      for all patients. However, the future of laryngotracheal reconstruction is
      promising with ongoing development of innovative techniques for repair, as well
      as the prospect of laryngeal transplantation.

PMID- 8525840
TI  - Experimental tracheal revascularization and transplantation.
AB  - Vascularized tracheal allografts would expand the domain of tracheal
      reconstructive surgery. The functional capability of vascularized tracheal
      allografts is closely correlated with immunologic parameters contributing to
      graft survival, about which little information is currently available. An
      orthotopic transplant model was developed that allows assessment of allograft
      function by examining healing at the graft-host junction and graft integrity
      during normal respiration.

PMID- 8525841
TI  - In vitro studies of human skeletal muscle: hormonal and metabolic regulation of
      glucose transport.

PMID- 8525842
TI  - [Philippe-Charles Schmerling (1790-1836) reveals the antiquity of man thanks to
      antediluvian deposits of the Liege caves].
AB  - Philippe-Charles Schmerling, often considered as the founder of paleontology, was
      undoubtedly a prominent personality in the province of Liege. The author evoques
      the beginning of paleontologic and prehistoric research in Wallonia through the
      biography and the analysis of Schmerling's works. Some of his contributions were
      completely disregarded, especially in the field of paleopathology where he can
      really be considered as a founder. Posterity will mainly retain his assertion
      about the contemporaneity of mankind with extinct animal species.

PMID- 8525843
TI  - [McLean's theory. Which brain model for which psychiatric practice?].
AB  - The aim of this paper is to present the evolutionary considerations of McLean
      about the "Triune Brain". This author described by this term a hierarchy of three
      brains-in-one, consisted by three evolutionary formations, radically different in
      structure and in chemistry. They are characterized as reptilian, paleomammalian,
      and neomammalian. Each of them plays an important role in the regulation of
      behavior, but there heterogeneity can induce schizophreniform ideas and feelings.
      Mc Lean speculations about Psychiatry emphasize genetic and biological factors in
      the genesis of mental disorders and lead to neglect the role of socio-cultural
      and familial factors.

PMID- 8525844
TI  - [Comparative biochemistry of the triune brain].
AB  - The contribution of the phylogenesis to the study of the functional organisation
      of brain constitutes an essential component in the integration of the current
      data regarding the knowledge of the central nervous system. The three evolutive
      structures evidenced by McLean allowed manifestation of a biological diversity
      particularly expressed in the neommamalian brain. Studying this biological
      diversity constitutes one of the field of comparative biochemistry. In this
      article, the authors attempt to characterize evolution through the study of GABA
      receptors.

PMID- 8525845
TI  - [The long progress of neurohypophyseal peptides].
AB  - Two neurohypophyseal peptides (vasopressin or antidiuretic hormone and oxytocin)
      belong to a family of peptides that are broadly widespread in the animal kingdom.
      These peptides are already found in unicellular species and differently
      distributed in hydra. Schematically, basic peptides related to vasopressin can be
      distinguished from neutral peptides related to oxytocin. Phylogenetic evolution
      of these two peptides shows that basic compounds are usually implicated in water
      metabolism regulation, but also through their central way of action, in important
      behaviour connected with survival of mankind (alertness, memorization,
      cardiovascular acceleration...) although neutral compounds are implicated in
      reproductive functions (carriage of spermatozoids in female genital tractus,
      expulsion phase of delivery, milk ejection reflex). Concerning behaviour, these
      compounds demonstrate properties favouring between subjects relationship
      (maternal behaviour settlement, including in birds, building of social links).
      Neuropsychiatric disturbances leading to an excess or a deficit of the central
      production of one of the groups of these neuropeptides could then be explained on
      basis of these general conclusions.

PMID- 8525846
TI  - [Phylogeny of sleep stages].
AB  - The states of sleep in man (orthodox and paradoxical sleep) are the achievement
      of a long evolution which has successively integrated several mechanisms. The
      circadian clock (predictive homeostasis) a system responsible for saving energy
      utilisation, a mechanism which adapts the duration of sleep to the preceding
      duration of waking (reactive homeostasis) and finally the apparition of an
      ultradian pace maker in homeothermic mammals which will be responsible for
      dreaming in man.

PMID- 8525847
TI  - [Ethological analysis of behavior and the emergence of ethics].
AB  - The problem of the emergence of ethical conduct is considered in the perspective
      of the neo-darwinian scheme and thus of the survival value of actions complying
      to this definition. After a brief recall of basic ethological principles, the
      applications of the cultural character to certain behaviour patterns of primates
      is analysed and introduces the concept of value. The emergence of symbolic and
      reflexible language in the course of the evolution of the ancestors of Homo
      sapiens is discussed. The ethical order is defined as a code liable to qualify
      actions which were originally programmed. The consequences of this duality of
      codes governing a same action are discussed.

PMID- 8525848
TI  - [Phylogenetic origin of symptoms in psychopathology. Exemplified by hysteria].
AB  - Setting behavioral disturbances affecting humans in a natural environmental
      context indicates the presence of phylogenetic components in their etiology.
      Hysterical conversion disorders provide a good illustration. The biological model
      to which they can be traced seems to be the "distraction display," originally
      intended to deceive predators and lure them away from the offspring or threatened
      related individuals. Hysterical tendance to draw attention on oneself could thus
      paradoxically be seen as performing an altruistic function.

PMID- 8525849
TI  - [Freud, precursor of ethology, between Darwin and MacLean].
AB  - We often forget Freud's share for zoology. Many primary ideas are issued from
      "Expression of Emotions in Man and Animals". The general attitude is
      evolutionistic, with his reasoning in becoming, fixation-regression, ontogeny and
      history in Man. This attitude is found again on its neurological side in MacLean
      and his verbal translation of cerebral levels.

PMID- 8525850
TI  - [Anthropological medicine: myth and reality].
AB  - After discussing the term "anthropologist doctor", the author describes the hard
      job of the psychiatrist in the penitentiary in Lantin. From the historical
      account of the penitentiary anthropology service, he establishes that this
      service has never had the necessary financial means to create and run
      laboratories of penitentiary anthropology, especially after the law for social
      defence was voted and enforced. He fears that, for want of money, the creation
      now of observation and treatment services would reduce the time one could spend
      working with prisoners in psychiatric wards. He deals briefly with the condition
      of psychopaths and drug-addicts in prisons.

PMID- 8525851
TI  - [The Social Protection Law].
AB  - Different levels of possible psychiatrist's mediations in Belgian legal
      procedures are detailed and a functional analysis of the first July 1964 Social
      Protection Law is proposed. The role of each participant is defined and
      commented. This is followed by a review of the recognized psychiatric pathology
      in a daily practice with confined patients in a social protection hospital.
      Finally, comparisons between DSM III-R diagnoses of confined patients and
      patients hospitalized in a local psychiatric hospital underlines the differences
      between these two institutions.

PMID- 8525852
TI  - [Psychopathy and drug addiction].
AB  - The author presents a study comparing psychopathic personality and drug addiction
      with regard to diagnosis, aethiopathogenia and treatment. Two third of drug
      addicts have associated personality disorders related to psychopathic disorders.
      Treatment on Therapeutic Communities provides a good alternative to both
      treatments in out patients or in open care units. The results obtained support
      the value of such a system in discussions about the taking over of patients in
      Social Defense Institutes and in jails.

PMID- 8525853
TI  - Drug compliance and cognitive-behavioral therapy in schizophrenia.
AB  - The cognitive-behavioral profession provides a theoretical model to understand
      the drug-compliance problem in schizophrenia and to enhance its therapeutic
      approach. The main components of this approach include continuous behavioral
      analysis, enhancement of therapeutic alliance, psychoeducation of the patient and
      significant others, perceptual and attitudinal strategies, behavioral strategies
      and cognitive restructuring.

PMID- 8525854
TI  - Medication response to ECT-resistant melancholic patients.
AB  - During an ongoing study on potential neurochemical and neuroendocrine predictors
      of recovery after ECT, it was observed that depressed patients with unfavorable
      response to ECT, improved consequently with antidepressants alone or in
      combination and in some cases with the addition of neuroleptics or lithium salts.
      13 female depressed patients with melancholia (DSM-III criteria), who had proven
      resistant to electroconvulsive therapy (ECT) and showed marked improvement with
      subsequent psychopharmacologic regimens, are described. In not less than 2 months
      after the last ECT, remission was achieved with a heterocyclic antidepressant
      (HCA) alone (3 patients) combined infusion of chlorimipramine and maprotiline (3
      patients) combined HCAs-antipsychotics (4 patients) and HCAs in combination with
      lithium (3 patients). It is worth noting that certain depressed patients improved
      markedly with drugs which had poor results at the same doses before ECT.
      Confirmation of these observations by prospective studies would provide novel
      therapeutic capabilities and clues about the mode of action of this controversial
      treatment.

PMID- 8525855
TI  - [Prevalence of autistic states in a cohort of very young children followed up in
      home care].
AB  - It is hypothesized that infantile autism could represent a defensive position
      with variable clinical characteristics whose expressions are notably influenced
      by the environment. We examined a group of ten children under the age of three
      who were followed up on home care. Our research focused on a double-blind
      correlation test between two types of data: the diagnostic on the one hand and
      the child video recording observation on the other hand. Certain objectivable
      autistic states were found in two children for which the initial diagnosis of
      autism were in a first time ruled out (according to DSM-III-R and French
      Classification). This confirms the polymorphism of children autistic states.

PMID- 8525856
TI  - Moclobemide and sertraline in the treatment of depressive disorders: a
      comparative study.
AB  - The efficacy and tolerability of moclobemide and sertraline were compared in a 13
      week trial on 55 depressive patients. Patients were diagnosed according to DSM
      III-R criteria using SCID (Structured Clinical Interview for DSM-III-R). The
      study group was composed of 48 patients with major depression and 7 with minor
      depression. Patients were randomized in two drug groups and raters were blind to
      the drugs patients used. HDRS and CGI were used to assess the change in
      depressive symptoms. Twenty seven patients received moclobemide and 28 patients
      received sertraline. The dose of moclobemide used was 300-600 mg/day and that of
      sertraline was 50-200 mg/day. At the end of 13 weeks mean drop in HDRS for the
      overall group was 14.78 and the response rate calculated as percentage of
      patients showing a 50% drop in HDRS score was 77.8. The response rate was 76.5%
      for moclobemide and 78.5% for sertraline. The difference was not significant. The
      side effects were assessed by using UKU Side Effects Rating Scale. The most three
      observed side effects were dry mouth, headache and insomnia.

PMID- 8525857
TI  - [Relationship between anhedonia, affective dependency and autonomy in health
      subjects].
AB  - Several authors have suggested that anbedonia, autonomy and interpersonal
      dependency could characterize personality of subjects prone to depression. We
      have studied in a group of 117 healthy subjects the Pearson correlation
      coefficients between two anbedonia scales (Physical Anbedonia Scale or PAS,
      Fawcett Clark Pleasure Capacity Scale-Physical Pleasure or FCPCS-PP) and the
      three sub-scales of the Interpersonal Dependency Inventory (IDI) (two rating
      dependency and one rating autonomy). The results have shown a significant
      correlation between the PAS and the autonomy sub-scale of the IDI. Anbedonia and
      autonomy could characterized a particular profile of personality.

PMID- 8525858
TI  - Risks associated with childbearing in schizophrenia.
AB  - The authors report about the catamnestic study of 919 schizophrenic women who
      gave birth to a child after their first schizophrenic episode, 112 (12.2%) of the
      patients suffered a new psychotic breakdown in connection with generation
      process. The overwhelming majority, 109 (11.9%) decompensated during the post
      partum periode (within 6 months after parturition). In a significantly lesser
      degree, 3 (0.32%) of the cases, the psychotic episode occurred during pregnancy
      (in the first trimester). The authors emphasize the importance of careful
      pharmacological and psychotherapeutical management of pregnant schizophrenic
      women.

PMID- 8525859
TI  - [Alice's nightmare. Analysis of a severe case of hysteria].
AB  - This report illustrates the difficult differential diagnosis between severe
      hysteria and psychosis in a young adult in crisis, and the need to elucidate the
      existing structure underlying the therapeutic approach. Alice's history will be
      the subject to a theoretic-clinic discussion. It allows to bring out important
      concepts to support an hypothesis of a neurotic decompensation.

PMID- 8525860
TI  - [Use of the genogram in the day care center: how the personal and familial
      history provides sense to time arrested].
AB  - This paper is about a therapeutic group created 3 years ago in our psychiatric
      day care unit: the genogram group. We will explain first how was born the idea of
      a work based on familial history and relationship, and how it was organised in
      practice. Then, we will speak about genogram interpretation and the different
      themes that the genogram can reveal: the nuclear family, the familial culture
      (her myths, her repeating model), the familial life cycle. We will also expose
      the theoretical models on which are based these themes. Finally, we will present
      our observations based on the experience with this group and about the
      characteristics and advantages of his use in institution.

PMID- 8525861
TI  - [The biological basis of suicidal behavior: neuroendocrine and
      psychophysiological approach to the role of catecholamines].
AB  - The current main neurochemical theories of the biological correlates of suicidal
      behavior principally involve the serotonergic system. Few data are available
      about the possible role of the catecholaminergic (noradrenergic and dopaminergic)
      function. In the present study, in a first part, we assessed the growth hormone
      (GH) response to clonidine, a selective alpha 2-adrenergic agonist, and to
      apomorphine, a dopaminergic agonist, in 22 DSM-III-R major depressive male
      inpatients with a history of suicide attempts compared to 22 age-matched major
      depressive inpatients without history of suicidal behavior. Hormonal responses to
      clonidine and apomorphine were also compared with 4.00 PM postdexamethasone
      cortisol levels. The two groups differed significantly in the GH peak response
      after apomorphine: 6.27 +/- 3.18 ng/ml in suicide attempters vs 17.40 +/- 14.87
      ng/ml in nonattempters (F = 11.78, p = 0.001). There was no statistically
      significant difference between the two groups for GH peak responses after
      clonidine. Moreover, mean postdexamethasone cortisol levels did not exhibit any
      significant difference between suicide attempters and nonattempters. Violent and
      nonviolent attempters did not differ on any of the biological measures. In a
      second part, P300 and contingent negative variation (CNV) were recorded in 20
      depressive inpatients subgrouped into suicide attempters (n = 10) and
      nonattempters (n = 10). The results showed a significant reduction of both P300
      and CNV amplitudes in patients who attempted suicide compared to patients without
      history of suicide attempts. Moreover, a significant correlation was found
      between the Suicidal Risk scale and CNV amplitude. In conclusion, these results
      suggest that a dopaminergic hypoactivity as assessed by a blunted GH response to
      apomorphine and by a reduction of both P300 and CNV amplitudes, could be
      considered as a biological correlate of suicidal behavior. In contrast,
      noradrenergic disturbances, particularly at the level of alpha 2-adrenergic
      receptors, seem to play a more minor role. Moreover, DST nonsuppression cannot be
      considered as a biological marker of suicidal behavior.

PMID- 8525862
TI  - [Decrease in the frontal-superobasal metabolic ratio in unipolar depression].
AB  - Cerebral frontal glucose metabolism was investigated in 12 unipolar depressed
      patients and compared to these of 12 healthy volunteers using Positron Emission
      Tomography (PET) and (F18) fluorodeoxyglucose. The PET investigation was made in
      a quiet room with a dimly light and each subject remained in a resting state with
      closed eyes. Results show a decreased in a frontal superobasal calculated ratio
      in depressed patients compared to control subjects for left and for right values.
      This reduction indicates an imbalance between the frontal and the superobasal
      region. This imbalance could relate to some particular depressive symptom
      profile.

PMID- 8525863
TI  - [Retrospective study of restraining measures in a population of patients admitted
      under a regimen of involuntary commitment].
AB  - The application of the 06-26-1990 law for the protection of mentally ill persons
      has confronted the psychiatrists working in general psychiatry wards with the
      problem of keeping up patients hospitalized against their own will and following
      a judiciary authority decision. Having to deal with this problem, the authors
      first reviewed the literature about the use of restraint techniques in
      psychiatry. They observed that these universally used techniques were strikingly
      denied in the psychiatric literature so that their accurate application was made
      difficult because of the lack of information about their indications, contra
      indications and application modalities. Afterwards, the authors have compared the
      different restraint techniques in a retrospective study over a one year period
      among voluntarily hospitalized patients and patients admitted against their wil
      in application of the 06-26-1990 law. They reported that the application of the
      law undoubtedly increased the number of restraint but did not modify either the
      population characteristics of the treatment modalities. These results have to be
      further confirmed in a prospective study.

PMID- 8525865
TI  - Special volume: Discrete and continuous information processing.

PMID- 8525864
TI  - [The controversy of depression in black Africa: a study of cultural causes].
AB  - Epidemiological data about depression in Africa are contradictory. Until the
      fifties, an almost absence of depression was reported in the studied population
      and from the fifties till today, a prevalence comparable to these of others
      continents is found. The authors discussed methodological and technical grounds
      susceptible to explain this controversy, with a special focus on cultural factors
      according to the parental and way of thinking of the Kongos in Zaire.

PMID- 8525866
TI  - Overlapping stage models and reaction time additivity: effects of the activation
      equation.
AB  - Many experimental factors have been found to affect mean reaction time (RT)
      additively in factorial experiments. What sorts of RT models are compatible with
      this fact? Sternberg (1969) showed that serial, discrete-stage models are
      consistent with additivity, and as a result additivity has sometimes been
      regarded as evidence in favor of such models. However, McClelland (1979) showed
      that an alternative "cascade" model, which violates crucial assumptions of
      discrete-stage models, also predicts RT additivity in many cases. This article
      examines various modified versions of the cascade model, and shows that mean RT
      additivity arises from many overlapping stage models, including some with
      thresholds, information quantization, and nonlinear activation transformations.
      This suggests that other aspects of the data besides mean RT additivity should be
      examined to distinguish between serial and overlapping stage models.

PMID- 8525867
TI  - Bisecting RT with lateralized readiness potentials: precue effects of LRP onset.

PMID- 8525868
TI  - Where did you go wrong? Errors, partial errors, and the nature of human
      information processing.
AB  - Human performance is seldom perfect, and even when an overt response is correct
      it may be accompanied by partial-error activity that does not achieve the level
      of a complete incorrect response. Partial errors can be detected in measures of
      the lateralized readiness potential, of the electromyogram, and of response
      force. Correct responses accompanied by partial errors tend to have slower
      reaction times than "clean" correct responses (because of response competition),
      and condition differences in reaction time can, on some occasions, be explained
      in terms of differences in the incidence of partial errors. In two-choice
      reaction time tasks, partial errors are more frequent when the imperative
      stimulus contains information that favors both responses, than when it contains
      information that favors only one response. The non-random nature of partial
      errors supports the inference that partial information about the stimulus is used
      to guide responses. A similar inference is supported by the observation that, in
      hybrid choice Go/No-go tasks, the kinds of partial errors that follow a No-go
      stimulus represent activation of the response that would have been correct had
      the stimulus been a Go stimulus. Finally, we note that the human processing
      system is capable of monitoring its own behavior and of initiating remedial
      actions if necessary. The activity of an error-detection system, as revealed by
      measures of the error-related negativity, is related to the degree to which
      responses are slowed after errors.

PMID- 8525869
TI  - The availability versus the use of partial information: multiple levels of
      selective processing between perception and action.
AB  - Temporal overlap of cognitive processes occurs when partial information about a
      stimulus activates associated responses before the stimulus has been fully
      identified. Recent evidence obtained with psychophysiological measures suggests
      that such overlap sometimes does, and sometimes does not occur. In this
      contribution, we argue that in order to understand why, we have to distinguish
      between selection of partial information for perception and selection of partial
      information for control over activation of responses. We discuss several
      mechanisms and factors that may modulate the temporal overlap of mental processes
      because they selectively influence the perceptual availability or the use of
      partial information.

PMID- 8525870
TI  - Continuous versus discrete information processing in pattern recognition.
AB  - A discrete feature model (DFM) and the fuzzy logical model (FLMP) were formulated
      to predict the distribution of rating judgments in a pattern recognition task.
      The distinction was between the spoken vowels /i/ and /I/, as in beet and bit.
      Subjects were instructed to rate the vowel on a nine-point scale from /i/ to /I/.
      Two features, the first formant frequency (F1) and the vowel duration, were
      orthogonally varied: The vowel /i/ has a lower (F1) and a longer duration
      compared to a somewhat higher (F1) and shorter duration for /I/. The DFM predicts
      that the separate features are recognized discretely, whereas the FLMP assumes
      that continuous information is available about each feature. Tests of these
      models on the observed data indicated that the continuous information assumption
      of the FLMP gave a significantly better description of the distribution of rating
      judgments.

PMID- 8525871
TI  - Discrete vs. continuous processing: the fate of an incompletely processed
      perceptual dimension.
AB  - A relevant issue in the debate on continuous vs. discrete processing of
      information is whether incompletely processed information does or does not affect
      a subsequent reaction. Two stimuli (SL, SR) were presented on eye level,
      subtending a visual angle of 45 degrees. SL was always inspected first, followed
      by a saccade to SR and finally by a same/different response. The fixation time of
      SL (TL), the saccadic time (TM) and the time from fixating SR to the response
      (TR) were separately measured. SL and SR consisted of two-dimensional stimuli
      (size and letter shape) constructed in such a way that encoding size took longer
      for one group and encoding shape took longer for another group of 10 subjects.
      All subjects were tested in three conditions: Shape was relevant in one, size in
      the second, and both dimensions were relevant in the third condition. TL was less
      when encoding the relevant dimension was fast. When both dimensions were
      relevant, TL was about as long as when only the slow dimension was relevant,
      suggesting parallel and interference-free processing during TL. When only the
      slow dimension was relevant, TR (same) was much longer when the fast dimension
      differed. When the fast dimension was relevant, TR (same) was slightly longer
      when the slow dimension differed, which can be handled by either model. The
      experiment was repeated with three well-practiced and less variable subjects who
      carried out sufficient trials to measure TR as a function of TL. The results of
      this study were in line with the discrete model: A different slow and irrelevant
      dimension did not affect the same response regardless of the duration of TL.
      Interestingly, subjects were capable of retrieving the slow dimension, suggesting
      a code which can be used for retrieval but which does not affect the
      same/different response.

PMID- 8525872
TI  - Speed-accuracy decomposition yields a sudden insight into all-or-none information
      processing.
AB  - The existence of discrete all-or-none information processing has often been
      assumed as a basis for stage models and also as an important characteristic of
      nonlinear connectionist models; however, there has been little or no hard
      empirical evidence supporting the existence of this phenomenon. In search of such
      evidence, we applied speed-accuracy decomposition (Meyer et al., 1988), a
      technique for detecting partial response information, to the examination of the
      time-course of processing in a (Gestalt) insight-like task, namely, anagram
      solution. This task was chosen because the Gestalt psychologists conjectured that
      insight is a sudden, discrete phenomenon. Supporting this view, we found little
      or no evidence of partial information in two experiments, thereby providing what
      may be the strongest evidence to date for all-or-none processing.

PMID- 8525873
TI  - Does perceptual analysis continue during selection and production of a speeded
      response?
AB  - This study asked whether perceptual analysis of a stimulus can continue while a
      response to this stimulus is being generated. In Experiment 1, subjects rapidly
      named a word that was visually degraded with superimposed pixels. Near the time
      of response, degradation was removed for a short time and then followed by a
      mask. Subjects then made a second, unspeeded judgment about the identity of the
      word. Unspeeded judgments were more accurate, showing that the degradation-free
      stimulus exposure was processed. In Experiment 2, the task was the same, but the
      degradation was gradually faded out for an individually adjusted duration.
      Comparison of unspeeded-response accuracy on trials with and without a speeded
      response showed that stimulus analysis continued at full efficiency during
      speeded-response generation. The results support conclusions of Rabbit and Vyas
      (1981) that perceptual analysis continues during response stages. This form of
      continuous processing does not necessarily contradict discrete stage models of
      human information processing, however.

PMID- 8525874
TI  - Perception-action coupling and S-R compatibility.
AB  - How is an aiming movement toward a visual target amended when the target suddenly
      steps to a new position just before or after the movement has started? Three
      hypotheses are examined: (1) the initial movement needs to be actively terminated
      before the new movement can be planned and executed, (2) substitution of the
      initial target position code results, after a normal RT, in the simultaneous
      termination of the initial movement and initiation of the movement to the new
      target position, or (3) a second movement from the initial to the second target
      is initiated after a normal RT, and superimposed on the ongoing movement toward
      the initial target. The substitution hypothesis assumes a highly continuous and
      parallel mode of operation of the perceptual-motor system, whereas the other
      hypotheses assume a distinctly discrete mode of operation. Detailed analyses of
      double-step movement trajectories clearly favored the substitution hypothesis.
      These results are discussed with reference to current views on motor control,
      overlapping-task performance, and the discrete-continuous issue. It is argued
      that the nature of the perception-action interface depends on the ideomotor
      compatibility of the task. Perceptual and motor processes operate in a highly
      continuous and parallel fashion in ideomotor compatible tasks, whereas the
      interposition of a limited-capacity response selection mechanism results in a
      discrete and intermittent mode of communication between these processes in non
      ideomotor compatible tasks.

PMID- 8525875
TI  - On-line visual control of aiming movements?
AB  - Two experiments are reported which addressed the flexibility of visuo-motor
      processing by manipulating the availability of visual information while executing
      a discrete aiming movement. The flexibility of visuo-motor processing was tested
      by unexpectedly changing the proportion of the movement trajectory that visual
      feedback was present. Visual feedback was manipulated for a short (0.30), medium
      (0.60) or long (0.90) proportion of the trajectory within a block of trials. Each
      of these three proportions of vision occlusion (Experiment 1) or visual
      disclusion (Experiment 2) during the initial trajectory was examined. Within a
      visual condition, one of the three visual feedback proportions occurred with a
      high probability (p = 0.72), whereas the remaining two proportions each occurred
      with a low probability (p = 0.14). The results clearly indicated that spatial
      accuracy was determined by the actual vision period, independent of its
      probability of occurrence. The data are consistent with a model of continuous on
      line control of movement execution.

PMID- 8525876
TI  - Cross-task cross talk in memory and perception.
AB  - The application of the additive factors method depends on finding factors that
      selectively influence processing stages. When all the processes for a task are in
      series, a factor directly influencing a process might change its output and
      thereby have indirect influence on succeeding processes. We investigate whether
      such indirect influence is possible between processes associated with different
      tasks being performed together. In two dual-task memory scanning and arithmetic
      experiments with digits as the stimuli for both tasks, information relevant for
      only one of the tasks nonetheless affected performance of the other. When the
      same digit was relevant for the two tasks, cross-task facilitation and
      interference were observed in some cases. Displaying the same digit for both
      tasks led to relatively fast response times, paralleling the effect of flankers
      in the response competition paradigm. But repetition of digits in memory slowed
      responses. It is suggested that the need for control processes to keep task
      information segregated is responsible for the pattern of effects.

PMID- 8525877
TI  - The role of neuroimaging in the discovery of processing stages. A review.
AB  - In this contribution we show how neuroimaging methods can augment behavioural
      methods to discover processing stages. Event Related Brain Potentials (ERPs),
      Brain Electrical Source Analysis (BESA) and regional changes in cerebral blood
      flow (rCBF) do not necessarily require behavioural responses. With the aid of
      rCBF we are able to discover several cortical and subcortical brain systems
      (processors) active in selective attention and memory search tasks. BESA
      describes cortical activity with high temporal resolution in terms of a limited
      number of neural generators within these brain systems. The combination of
      behavioural methods and neuroimaging provides a picture of the functional
      architecture of the brain. The review is organized around three processors: the
      Visual, Cognitive and Manual Motor Processors.

PMID- 8525878
TI  - Neural correlates of partial transmission of sensorimotor information in the
      cerebral cortex.
AB  - Using single neuron recordings in monkey primary motor (MI) cortex, two series of
      experiments were conducted in order to know whether response preparation can
      begin before perceptual processing finishes, thus providing evidence for a
      temporal overlap of perceptual and motor processes. In Experiment 1, a
      "left/right, Go/No-Go" reaction time (RT) task was used. One monkey was trained
      to perform wrist flexion/extension movements to align a pointer with visual
      targets. The visual display was organized to provide a two-dimensional stimulus:
      side (an easy discrimination between left and right targets) which determined
      movement direction, and distance (a difficult discrimination between distal and
      proximal targets) which determined whether or not the movement was to be made.
      Changes in neuronal activity, when they were time-locked to the stimulus, were
      almost similar in the Go and No-Go trials, and when they were time-locked to
      movement onset, were markedly reduced in No-Go as compared to Go trials. In
      Experiment 2, a stimulus-response compatibility (SRC) task was used. Two monkeys
      were trained to align a pointer with visual targets, on either left or right. In
      the spatially "compatible" trials, they had to point at the stimulus position,
      whereas in the "incompatible" trials, they had to point at the target located in
      the opposite side. For 12.5% of neurons, changes in activity associated with
      incompatible trials looked like changes in activity associated with movements
      performed in the opposite direction during compatible trials, thus suggesting the
      hypothesis of an automatic activation of the congruent, but incorrect response.
      Results of both experiments provide evidence for a partial transmission of
      information from visual to motor cortical areas: that is, in the No-Go trials of
      the first task, information about movement direction, before the decision to
      perform or not this movement was made, and, in the incompatible trials of the SRC
      task, information about the congruent, but incorrect response, before the
      incongruent, but correct response was programmed.

PMID- 8525879
TI  - The temporal selectivity of additive factor effects on the reaction process
      revealed in ERP component latencies.
AB  - An experiment was conducted to relate individual components of the event-related
      brain potential to specific stages of information processing in a two-choice
      reaction time (RT) task in a group of undergraduate students. Specifically, the
      latency of the P300 component and the lateralized readiness potential (LRP) were
      studied as a function of variations in stimulus degradation and response
      complexity. It was hypothesized that degrading the stimulus would delay the P300
      and LRP to the same extent as RT, and that increasing response complexity would
      affect RT but not P300 latency. The extant literature did not permit any
      hypothesis regarding the effect of response complexity on LRP latency. The two
      task variables were found to have additive effects on RT. As predicted,
      variations in stimulus degradation influenced the latencies of both components,
      whereas alterations in response complexity had no effect on P300 latency. A
      significant new finding was that the onset latency of the LRP remained unchanged
      across levels of response complexity. The overall pattern of results supports the
      notion of temporal selectivity of stage manipulations that is derived from
      discrete stage models of human information processing. Furthermore, these results
      refine the functional interpretation of the LRP by indicating that within the
      conceptual framework of a stage model the processes this component indexes
      succeed the start of response choice but preceded the start of motor programming.

PMID- 8525880
TI  - Proceedings of the 7th International Congress of Mucosal Immunology. Prague,
      Czechoslovakia, August 16-21, 1992.

PMID- 8525881
TI  - Induction and recall of the secondary immune response entirely in tissue culture.

PMID- 8525882
TI  - Intraperitoneal administration of tetanus toxoid elicits a specific response of
      antibody-secreting cells in the peritoneal cavity.

PMID- 8525883
TI  - The colon and rectum as inductor sites for local and distant mucosal immunity.

PMID- 8525884
TI  - A basement membrane molecule preferentially associated with mucosal post
      capillary venules.

PMID- 8525885
TI  - Analysis of intraepithelial lymphocytes and Peyer's patch lymphoid tissue in TCR
      alpha knockout mice.

PMID- 8525886
TI  - Intestinal T cells in CD8 alpha knockout mice and T cell receptor transgenic
      mice.
AB  - Intraepithelial lymphocytes (IEL) refer to the T cells located at the epithelium
      of the intestines. Unlike the T cells in other peripheral lymphoid organs, the
      majority of IEL express the CD8 cell surface protein. To study the role of CD8 in
      the ontogeny and the function of IEL, phenotypic analysis of IEL from CD8 alpha
      knockout mice and normal mice was performed. The CD8 alpha gene in CD8 alpha
      knockout mice was disrupted by homologous recombination. These mice are defective
      in thymic maturation of cytotoxic T cells. In normal mice, alpha beta T cells
      that were CD8 alpha alpha+ or CD4+ CD8 alpha alpha+, and gamma delta T cells that
      were CD8 alpha alpha+, were the distinct populations found only in IEL. In CD8
      alpha knockout mice, the population size of IEL remained normal, but the majority
      of IEL were CD4- CD8- T cells expressing alpha beta or gamma delta T cell
      receptors. IEL from the H-Y transgenic mice2, which express the male H-Y antigen
      specific T cell receptor in a normal and in a CD8 alpha-null background, were
      also studied. In contrast to thymic derived T cells, CD8 alpha alpha+ IEL with
      the autoreactive transgenic T cell receptor were not deleted, but clonally
      expanded in the male transgenic mice. Interestingly, no pathological symptoms
      were observed in the intestines of these mice. In the absence of CD8 alpha
      expression, the H-Y specific autoreactive IEL did not accumulate in the
      intestines. The results suggest that CD8 alpha alpha+ IEL are derived extra
      thymically and their responses towards antigens require the CD8 accessory
      molecule.

PMID- 8525887
TI  - Analysis of intestinal intraepithelial lymphocyte (IEL) T cells in mice
      expressing anti-CD8 immunoglobulin transgenes.

PMID- 8525888
TI  - Effect of neonatal thymectomy on murine small intestinal intraepithelial
      lymphocytes expressing T cell receptor alpha beta and "clonally forbidden V beta
      s".
AB  - Neonatal thymectomy NTX performed on Day 3 of C3H mice causes over a 50%
      reduction in small intestinal intraepithelial lymphocytes (IEL) expressing the
      alpha beta T cell receptor (TCR) when analyzed at 10 weeks of age. Furthermore,
      this reduction is most notable in alpha beta TCR IEL expressing the CD8 alpha
      homodimer and no Thy 1 marker. This is in direct contradiction to the present
      theory that alpha beta TCR IEL expressing these markers are thymic independent.
      Evaluation of V beta expression shows a relative increase in V beta s which are
      clonally forbidden (V beta s 3, 5, 11), and which is consistent with the
      extrathymic origin of these particular IEL.

PMID- 8525890
TI  - Minimal signal requirements for superantigen-specific T cell-driven B cell
      proliferation.

PMID- 8525889
TI  - Desialylation of rat intraepithelial lymphocytes: effects on proliferation and
      dipeptidyl peptidase IV activity.

PMID- 8525891
TI  - Expression of cell adhesion molecules in the fetal gut.

PMID- 8525892
TI  - A role for antigen in the evolution of gastrointestinal MALT-type B cell
      lymphoma.

PMID- 8525893
TI  - In vivo proliferation of T and B lymphocytes in the epithelium and lamina propria
      of the small intestine.

PMID- 8525894
TI  - Analysis of the second messenger systems involved in the synergistic effect of
      cholera toxin and interleukin-4 on B cell isotype-switching.

PMID- 8525895
TI  - Cytotoxic activity of T cells expressing different T-cell receptor variable gene
      products in the intestinal mucosa.

PMID- 8525896
TI  - B-cell promoting activity of human colostrum.

PMID- 8525897
TI  - Expression of adhesion molecules on the surface of malignant cells and cell
      lines.

PMID- 8525898
TI  - Ergot alkaloid-induced cell proliferation, cytotoxicity, and lymphokine
      production.

PMID- 8525899
TI  - Effect of corticosteroid on lymphocyte adhesion.
AB  - Pulse steroid therapy is utilised in the treatment of vasculitis and active
      rheumatoid arthritis. Decreased entry of lymphocytes to sites of cell-mediated
      immune reactions is well recognised, though the mechanism is not fully
      understood. It may involve adhesion to endothelium. We have therefore measured
      the effect of methylprednisolone on lymphocyte adhesion to porcine lamina propria
      endothelium. A marked decrease in adhesion was found after incubating cells at 4
      degrees C or at room temperature, with a clear dose response effect, from 0.46mM
      to 6.3mM. We have previously demonstrated binding of rheumatoid synovial fluid
      mononuclear cells to lamina propria endothelium. It is suggested that the
      ameliorating effect of steroid pulsing may be mediated by down-regulating adhesin
      expression of a gut-seeking population of cells.

PMID- 8525900
TI  - Adherence of rheumatoid lymphocytes to endothelium of lamina propria.

PMID- 8525901
TI  - Expression of SC, IL-6 and TGF-beta 1 in epithelial cell lines.

PMID- 8525902
TI  - Butyrate differentially affects constitutive and cytokine-induced expression of
      HLA molecules, secretory component (SC), and ICAM-1 in a colonic epithelial cell
      line (HT-29, clone m3).
AB  - In conclusion, we have found that physiological concentrations of butyrate
      increase the constitutive levels of HLA class I and SC molecules in HT-29m3
      cells. Moreover, butyrate at high concentrations induces de novo synthesis of HLA
      DR but not ICAM-1 molecules. Our data further showed that butyrate generally
      facilitates the cytokine-induced expression of immunological molecules in these
      cells but, interestingly, it specifically reduces the stimulatory effects of TNF
      and IL-4 on HLA class I and SC, respectively. We are currently studying how
      butyrate affects transcriptional regulation of the genes encoding these
      molecules. Further knowledge about the effects of butyrate in relation to gene
      regulation is required. It is possible that butyrate might interfere with
      specific, cytokine-dependent regulatory elements in certain genes which, in turn,
      could have implications for immune regulation of colonic epithelial cells in
      vivo.

PMID- 8525903
TI  - Cytokines induce an epithelial cell cytokine response.

PMID- 8525904
TI  - Modulation of the MHC class I and II molecules by bacterial products on
      intestinal epithelial cells.

PMID- 8525905
TI  - The effect of medium derived from activated peripheral blood mononuclear cells on
      two intestinal cell lines.

PMID- 8525906
TI  - The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at
      epithelial surfaces.
AB  - The L1 protein occurs at high concentrations in neutrophils, monocytes, certain
      reactive tissue macrophages, squamous mucosal epithelia, and reactive epidermis.
      It constitutes in fact about 60% of the neutrophilic cytosol protein fraction.
      The two L1 chains (L1H and L1L) are referred to by a bewildering collection of
      names, various authors having different preferences (MRP-8 and MRP-14; CFA or
      calgranulin A and B). The most recent proposal is calprotectin because of its
      calcium-binding properties and antimicrobial effect shown in vitro. L1 belongs to
      the S-100 protein family and may be involved in the regulation of keratinocyte
      proliferation and differentiation. It exists at high levels in blood and
      interstitial tissue fluid in several infectious, inflammatory, and malignant
      disorders, and it is released abundantly in foci of granulocytes and macrophages.
      The C-terminal sequence of the L1H chain has been shown to be identical to the N
      terminus of peptides known as neutrophil immobilizing factors. Such an activity
      of L1 could be important for the accumulation of vital granulocytes, while L1
      released from neutrophils, macrophages and epithelial cells might exert
      antimicrobial activity, perhaps by depriving microorganisms of zinc. The minimum
      inhibitory concentrations of L1 in vitro were found to be 4-32 mg/l for Candida
      albicans, 64 mg/l for Staphylococcus aureus, 64-256 mg/l for S. epidermidis, and
      256 mg/ml for Escherichia coli and Klebsiella spp. Killing was observed at 2-4
      times higher concentrations. In patients with HIV infection, those who developed
      oral candidiasis had significantly lower parotid L1 levels than those who did not
      (67 micrograms/l vs. 216 micrograms/l).

PMID- 8525907
TI  - Differential expression of leucocyte protein L1 (calprotectin) by monocytes and
      intestinal macrophages.

PMID- 8525908
TI  - Transforming growth factor beta (TGF beta) directs IgA1 and IgA2 switching in
      human naive B cells.

PMID- 8525909
TI  - Complement component C3 production and its cytokine regulation by
      gastrointestinal epithelial cells.

PMID- 8525910
TI  - The polymeric immunoglobulin receptor: signals for polarized expression.

PMID- 8525911
TI  - Neural, endocrine and immune regulation of secretory component production by
      lacrimal gland acinar cells.

PMID- 8525912
TI  - Antigen presentation by a mouse duodenal epithelial cell line (MODE-K).

PMID- 8525913
TI  - The regulation of IL-6 secretion from IEC-6 intestinal epithelial cells by
      cytokines and mucosally important antigens.

PMID- 8525914
TI  - Epithelial cells in sow mammary secretions.

PMID- 8525915
TI  - Microdissected domes from gut-associated lymphoid tissues: a model of M cell
      transepithelial transport in vitro.

PMID- 8525916
TI  - Evidence that membranous (M) cell genesis is immuno-regulated.

PMID- 8525917
TI  - A confocal microscopical analysis of Peyer's patch membranous (M) cell and
      lymphocyte interactions in the scid mouse.

PMID- 8525918
TI  - The modulation of class I and class II MHC molecules on intestinal epithelial
      cells at different stages of differentiation.

PMID- 8525919
TI  - Cryptdins: endogenous antibiotic peptides of small intestinal Paneth cells.
AB  - We purified three peptides ("cryptdins") from the small intestines of mice,
      established their primary amino acid sequences and examined their antimicrobial
      activity. Their primary sequences revealed approximately 50% identity to a group
      of antimicrobial defensins that we had previously isolated from the granules of
      rat neutrophils. In addition to their ability to kill Gram-positive (L.
      monocytogenes) and Gram-negative bacteria (E. coli and S. typhimurium) in vitro,
      the peptides were much more active against an avirulent (phoP) S. typhimurium
      strain than against its isogenic, mouse-virulent progenitor. Overall, these data
      suggest that endogenous antimicrobial peptides produced by Paneth cells may
      protect small intestinal crypts, which are critical sites of epithelial cell
      renewal, from invasion by autochthonous flora or by perorally acquired potential
      pathogens, such as Listeria and Salmonella.

PMID- 8525920
TI  - Physical interaction between lung epithelial cells and T lymphocytes.
AB  - The present results support a role for epithelial cells in the activation of T
      cells in an apparent antigen-independent manner. The transient expression of CD25
      indicates a short acting T cells activation. Possibly, this event primes T cells
      to respond swiftly upon antigen-specific stimulation or to synthesize mediators
      that affect the local milieu. The molecular mechanism of interaction, although
      not well defined possibly involves LFA3-CD2 interactions. In T cell activation,
      via LFA3-CD2 interaction, the density of presented LFA3 molecules is critical.
      With the increase in the level of expression of LFA3 by epithelial cells this
      critical density may have been reached. However, based on what is known about T
      cell activation and CD25 expression in particular it is likely that additional
      signals such as soluble mediators are required for T cell activation by
      epithelial cells. Whether this mode of activation occurs in vivo remains to be
      established by studying ex vivo and in situ material. Not much is known about the
      expression of LFA3 by epithelial cells in vivo, nor about the stimuli that induce
      the upregulation of LFA3. In preliminary experiments with fluorescence microscopy
      we found that neither TNF-alpha nor IL-1 beta induce LFA3 in the same fashion as
      IFN-gamma. In conclusion, T cell activation by epithelial cells could be an
      important feature in inflammatory and immunological processes in mucosal systems
      such as the bronchi and deserves further research.

PMID- 8525921
TI  - The role of lympho-epithelial interactions in the regulation of small intestinal
      epithelium proliferation.

PMID- 8525922
TI  - Lymphokine mRNA expression in the human intestinal mucosa and PBL determined by
      quantitative RT/PCR.

PMID- 8525923
TI  - Dendritic cells "in vivo": their role in the initiation of intestinal immune
      responses.

PMID- 8525924
TI  - Direct modulation of enterocyte growth by activated macrophages.

PMID- 8525925
TI  - Penetration of fluorescent neutrophils through cultured epithelium studied by
      confocal microscopy.

PMID- 8525926
TI  - Immunostaining with monoclonal antibodies to eosinophil cationic protein (EG1 and
      EG2) does not distinguish between resting and activated eosinophils in formalin
      fixed tissue specimens.

PMID- 8525927
TI  - The role of mast cells in intestinal immunophysiology.

PMID- 8525928
TI  - Modulation of tumour necrosis factor-alpha mRNA levels by interferons in
      different populations of mast cells.

PMID- 8525929
TI  - Aggregation of Thy-1 glycoprotein induces tyrosine phosphorylation of different
      proteins in isolated rat mast cells and rat basophilic leukemia cells.

PMID- 8525930
TI  - Effects of subdiaphragmatic vagotomy on mucosal mast cell densities in stomach
      and jejunum of rats.

PMID- 8525931
TI  - Mechanisms of NK recognition and activation based on lectin-saccharide
      interactions.

PMID- 8525932
TI  - Regulation of T cell reactivities by intestinal mucosa.

PMID- 8525933
TI  - Detection of cells with NK activity from histologically normal mucosa in relation
      to disease.

PMID- 8525934
TI  - Effects of mesalazine on lamina propria white cell functions.

PMID- 8525935
TI  - The significance of cultivating cells and hemopoietic tissue from tunicates.

PMID- 8525936
TI  - Perienteral chloragogen tissue and its role in defense in lumbricid worms.

PMID- 8525937
TI  - The spleen and its coelomic and enteric history.

PMID- 8525938
TI  - The fate of protein antigen in annelids--in vivo and in vitro studies.

PMID- 8525939
TI  - Hemolytic function of opsonin-like molecules in coelomic fluid of earthworms.

PMID- 8525940
TI  - Role of lectins (C-reactive protein) in defense of marine bivalves against
      bacteria.

PMID- 8525941
TI  - Bacterial antigen priming of marine fish larvae.

PMID- 8525942
TI  - Vector-encoded interleukin-5 and interleukin-6 enhance specific mucosal
      immunoglobulin A reactivity in vivo.

PMID- 8525943
TI  - Phylogeny of the immunogloblin joining (J) chain.

PMID- 8525944
TI  - Genital-associated lymphoid tissue in female non-human primates.
AB  - We investigated genital-associated lymphoid tissue (GENALT) in non-human primates
      (macaques), by augmenting vaginal with oral immunization. The vaccine was a
      recombinant particulate SIV antigen (p27:Ty-VLP), linked to CT-B, and
      administered into the vagina by a paediatric naso-gastric tube and into the
      stomach by a gastric tube. Oro-vaginal or vagino-oral sequence of immunization
      elicited specific CD4+ T cell proliferative responses to p27 antigen in the
      genital lymph nodes and the spleen but not in unrelated lymph nodes. CD4+ T cells
      reconstituted with B cells and macrophages from the genital lymph nodes induced
      specific IgA and to a lesser extent IgG anti-p27 antibodies. However, the
      corresponding splenic cells induced greater IgG than IgA antibody synthesis.
      Intramuscular immunization primed splenic but not genital lymph node cells, and
      induced CD4+ T cell proliferative responses and predominantly B cell IgG antibody
      synthesis. Finding primed B and T cells in the genital lymph nodes after
      augmenting vaginal by oral immunization provides experimental evidence for GENALT
      in non-human primates. This primate model of vaginal immunization suggests 3
      levels of specific immunity: (1) secretory IgA (and IgG) in the cervico-vaginal
      mucosal epithelium; (2) primed CD4+ T cells and B cells in the genital lymph
      nodes and the spleen; and (3) circulating CD4+ T cells, B cells and IgG and IgA
      antibodies specific to the immunizing antigen.

PMID- 8525945
TI  - Immunomorphologic studies of human decidua-associated lymphoid cells in normal
      early pregnancy.

PMID- 8525946
TI  - Immunocytes and cell-mediated immunity in the pathology of reproduction.

PMID- 8525947
TI  - Influence of estrous cycle and estradiol on mitogenic responses of splenic T- and
      B-lymphocytes.
AB  - Previous studies from our laboratory have shown that the stage of the estrous
      cycle and hormone treatment regulates the presence of immune cells in the female
      reproductive tract. The purpose of the present study was to determine whether sex
      hormones influence spleen cell responses to mitogens. The present study
      demonstrates that spleen cell responses to mitogens vary with the stage of the
      estrous cycle in intact rats. Further, our findings indicate that estradiol
      administered to ovariectomized animals increases the mitogenic response of spleen
      cells to both B and T lymphocyte mitogens.

PMID- 8525948
TI  - Secretory component production by rat uterine epithelial cells in culture.

PMID- 8525949
TI  - Human decidual CD7+ lymphocytes display a unique antigenic phenotype.

PMID- 8525950
TI  - Immune cells on intrauterine contraceptive devices.

PMID- 8525951
TI  - Cellular and humoral immunity to sperm in ovulatory cervical mucus from infertile
      women.

PMID- 8525952
TI  - Histology of the continuous Peyer's patches in the terminal ileum of pigs in the
      perinatal period.

PMID- 8525953
TI  - Embryonic liver: diversification site of lymphocyte lineages.

PMID- 8525954
TI  - Reticulum cells in the ontogeny of nasal-associated lymphoid tissue (NALT) in the
      rat.

PMID- 8525955
TI  - The production of TNF, IL-1 and IL-6 in cutaneous tissues during maturation and
      aging.

PMID- 8525956
TI  - Ontogeny of the mucosal immune response against different types of pneumococcal
      polysaccharide in rat.

PMID- 8525957
TI  - Increased mannose-specific adherence and colonizing ability of Escherichia coli
      083 in breast-fed infants.

PMID- 8525958
TI  - The influence of milk factors on the course of neonatal mouse crytosporidiosis--a
      preliminary report.

PMID- 8525959
TI  - Cellular and molecular biologic approaches for analyzing the in vivo development
      and maintenance of gut mucosal IgA responses.

PMID- 8525960
TI  - Persistent in vivo activation and transient anergy to TCR/CD3 stimulation of
      normal human intestinal lymphocytes.

PMID- 8525961
TI  - A dual origin for IgA plasma cells in the murine small intestine.

PMID- 8525962
TI  - Development of mucosal humoral immune responses in germ-free (GF) mice.

PMID- 8525963
TI  - Inhibition of bacterial translocation from the gastrointestinal tract to the
      mesenteric lymph nodes in specific pathogen-free mice but not gnotobiotic mice by
      non-specific macrophage activation.

PMID- 8525964
TI  - Expression of Thy-1 antigen in germ-free and conventional piglets.

PMID- 8525965
TI  - Transient appearance of circulating interleukin-6 and tumor necrosis factor in
      germ-free C3H/HeJ and C3H/HeN mice upon intestinal exposure to E. coli.

PMID- 8525966
TI  - Stimulation of intestinal immune cells by E. coli in gnotobiotic piglets.

PMID- 8525967
TI  - Immunomodulation of the gnotobiotic mouse through colonization with lactic acid
      bacteria.

PMID- 8525968
TI  - Expression of interleukin-2 receptor on enterocytes in conventional and germ-free
      rats after stimulation with gliadin.

PMID- 8525969
TI  - Functional lactoferrin receptors on activated human lymphocytes.

PMID- 8525970
TI  - Factors influencing the fate of Escherichia coli and Salmonella typhimurium in
      germ-free piglets and rats.

PMID- 8525971
TI  - Bifidobacteria and Escherichia coli translocation in gnotobiotic mice.

PMID- 8525972
TI  - Effects of Nocardia-delipidated cell mitogen on intestinal mucosa and spleen
      lymphocytes of germ-free rats.

PMID- 8525973
TI  - Stimulation of galt by Nocardia delipidated cell mitogen (NDCM) in irradiated
      germfree piglets.

PMID- 8525974
TI  - Mucosal adaptation and destruction in response to lamina propria T cell
      activation in explants of human fetal intestine.

PMID- 8525975
TI  - Development of IgE antibodies and T cell reactivity against intestinal bacterial
      antigens in rats and the influence of feeding.

PMID- 8525976
TI  - Expression of MHC class II antigens and enzymatic activity in enterocytes of germ
      free and conventional rats: dependence on nutritional factors during suckling.

PMID- 8525977
TI  - Quantification of salivary, urinary and fecal secretory IgA, as well as in saliva
      titers and avidities of IgA antibodies in children living at different levels of
      antigenic exposure and undernutrition.

PMID- 8525978
TI  - Alterations of GALT due to malnutrition and decrease in the secretory immune
      response to cholera toxin.

PMID- 8525979
TI  - Dietary antigen handling by mother and offspring in a two generation study.

PMID- 8525980
TI  - The effect of caloric supplementation on levels of milk IgA antibodies and their
      avidities in undernourished Guatemalan mothers.

PMID- 8525981
TI  - The effect of an elemental diet on gut-associated lymphoid tissue (GALT) in rats.

PMID- 8525982
TI  - Effect of bacterial antigens on local immunity.

PMID- 8525983
TI  - Intestinal and systemic immune responses in rats to dietary lectins.

PMID- 8525984
TI  - The effect of an anti-glucocorticoid (ZK 98299) on thymus evolution and on
      hydrocortisone-induced thymolysis, intestinal brush-border enzymes and their
      desialylation in suckling rats.
AB  - 1. The action in Onapristone infant male rats displays short-term and delayed
      effects. 2. Suppression of intestinal brush-border enzymes and increase of thymus
      mass were observed only immediately after 3-day treatment with Onapristone. After
      an additional 3 days its effect disappeared. There was no immediate or delayed
      effect of Onapristone on the desialylation of brush-border enzymes. 3. In the
      short-term and delayed effects, Onapristone suppressed the HC-provoked induction
      of several intestinal brush-border enzymes, especially alpha-glycosidases. In the
      delayed effect the drug also suppressed thymolysis induced by the exogeneously
      given glucocorticoid, and suppressed the HC-induced desialylation of a brush
      border enzyme DP IV, which serves as a marker of the desialylation process. 4.
      These experiments seem to support a conclusion that the postnatal development of
      intestinal brush-border enzymes and the development of thymus in infant rats are
      controlled by endogeneously secreted glucocorticoids. 5. The control of
      sialylation of intestinal brush-border proteins by endogeneously secreted
      glucocorticoids during the postnatal development of the rat remains debatable.

PMID- 8525985
TI  - A comparative study of the immune response to poly-[alpha(2-->8)-N-acetyl
      neuraminic acid].

PMID- 8525986
TI  - In vivo activation of extrathymic T cells in mice by staphylococcal enterotoxin
      B.

PMID- 8525987
TI  - Substance P promotes Peyer's patch and splenic B cell differentiation.

PMID- 8525988
TI  - Interaction of a sulfhydryl analogue of vasoactive intestinal peptide (VIP) with
      murine lymphocytes.

PMID- 8525989
TI  - Analysis of SP/VIP fiber association with T4 and T8 lymphocytes in normal human
      colon.

PMID- 8525990
TI  - Cholecystokinin-octapeptide (CCK-OP) and substance P (SP) influence immune
      response to cholera toxin in live animals.

PMID- 8525991
TI  - Neurite outgrowth induced by rat lymphoid tissues in vitro.

PMID- 8525992
TI  - Exercise, stress and mucosal immunity in elite swimmers.

PMID- 8525993
TI  - Structure of IgA: facts and gaps in our data on disulfide bonds.

PMID- 8525994
TI  - Intra- and inter-chain disulfide bridges of J chain in human S-IgA.

PMID- 8525995
TI  - Characterization of IgA1, IgA2 and secretory IgA carbohydrate chains using plant
      lectins.

PMID- 8525996
TI  - Human IgA1 and IgA2 have distinct spectrotypes but display subclass similarities
      between individuals.

PMID- 8525997
TI  - Peptic fragments of rat monomeric IgA.

PMID- 8525998
TI  - Antigenic and genetic heterogeneity among Haemophilus influenzae and Neisseria
      IgA1 proteases.

PMID- 8525999
TI  - Titration of inhibiting antibodies to bacterial IgA1 proteases in human sera and
      secretions.

PMID- 8526000
TI  - Cleavage of IgG and IgA in vitro and in vivo by the urinary tract pathogen
      Proteus mirabilis.

PMID- 8526001
TI  - The migration of peritoneal cells towards the gut.

PMID- 8526002
TI  - Cleavage of human immunoglobulins by proteinase from Staphylococcus aureus.

PMID- 8526003
TI  - Cloning, chromosomal localization, and linkage analysis of the gene encoding
      human transmembrane secretory component (the poly-Ig receptor).

PMID- 8526004
TI  - The covalent linkage of the secretory component to IgA.

PMID- 8526005
TI  - Mouse secretory component.

PMID- 8526006
TI  - Antibody production to secretory component (SC) using recombinant SC fragment.

PMID- 8526007
TI  - A lack of relationship between secretory component and galactosyltransferase in
      human milk.

PMID- 8526008
TI  - Substance P accelerates secretory component-mediated transcytosis of IgA in the
      rat intestine.

PMID- 8526009
TI  - New functions for mucosal IgA.

PMID- 8526010
TI  - Intracellular neutralization of Sendai and influenza viruses by IgA monoclonal
      antibodies.

PMID- 8526011
TI  - The binding of monomeric IgA to myeloid Fc alpha R: evidence for receptor re
      cycling and determination of its affinity.

PMID- 8526012
TI  - Signal transduction via Fc receptors; involvement of tyrosine kinase and redox
      regulation by ADF.

PMID- 8526013
TI  - A new IgA receptor expressed on a highly activated murine B cell lymphoma.

PMID- 8526014
TI  - Anti-inflammatory capacities of human milk: lactoferrin and secretory IgA inhibit
      endotoxin-induced cytokine release.

PMID- 8526015
TI  - HML-1, a novel integrin made of the beta 7 chain and of a distinctive alpha
      chain, exerts an accessory function in the activation of human IEL via the CD3
      TCR pathway.

PMID- 8526016
TI  - Inhibition of enteropathogenic Escherichia coli (EPEC) adherence to HeLa cells by
      human colostrum. Detection of specific sIgA related to EPEC outer-membrane
      proteins.

PMID- 8526017
TI  - Salivary specific antibodies in relation to adhesion of Streptococcus pyogenes to
      pharyngeal cells of patients with rheumatic fever and rheumatic heart disease.

PMID- 8526018
TI  - Entamoeba histolytica adherence: inhibition by IgA monoclonal antibodies.

PMID- 8526019
TI  - Biological properties of yolk immunoglobulins.

PMID- 8526020
TI  - Role of alpha-haemolysin in resistance of Escherichia coli strains to
      bactericidal action of human serum and polymorphonuclear leukocytes.

PMID- 8526021
TI  - Opsono-phagocytosis of non-encapsulated Haemophilus influenzae.

PMID- 8526022
TI  - Phenotype of HML-1-positive and HML-1-negative T lymphocytes in the human
      intestinal lamina propria.

PMID- 8526023
TI  - Adherence of porcine Peyer's patch, peripheral blood and lymph node lymphocytes
      to Peyer's patch lamina propria.

PMID- 8526024
TI  - Assessment of engraftment and function of human tonsillar and blood mononuclear
      cells in immunodeficient mice.

PMID- 8526025
TI  - In vivo switching: identification of germline transcripts for human IgA.

PMID- 8526026
TI  - Expression of VLA-4 and L-selectin in human gut-associated lymphoid tissue
      (GALT).

PMID- 8526027
TI  - Compartmentalization within the common mucosal immune system.

PMID- 8526028
TI  - Characterization of human CD34+ derived dendritic/Langerhans cells (D-Lc).

PMID- 8526029
TI  - In situ expression of activation markers by Langerhans' cells containing GM-CSF.

PMID- 8526030
TI  - Phenotypic variation and functional differences within dendritic cells isolated
      from afferent lymph.

PMID- 8526031
TI  - Expression of somatostatin on Langerhans cells.

PMID- 8526032
TI  - Dermal dendritic cells are important members of the skin immune system.
AB  - In conclusion we have shown that motile cells with a dendritic morphology can be
      isolated from dermis of normal and diseased human skin. DDC bear high amounts of
      MHC class II molecules on their surface, and are very potent antigen presenting
      cells. Subpopulations of these cells acquire certain ultrastructural features of
      Langerhans cells in-vitro such as Birbeck granule formation and CD1a expression.
      These newly defined members of the dendritic cell family of APCs may be
      precursors of epidermal Langerhans cells and may play a role in skin immune
      responses. Furthermore in inflammatory dermatoses such as psoriasis, a role in
      the autostimulation and cytokine production of T cells could be demonstrated.
      Given their number, distribution, and in-vitro functional capacity, it is
      appropriate at this time to conclude that DDCs are indeed important members of
      the skin immune system.

PMID- 8526033
TI  - Expression of CD44 antigen by Langerhans cells and Thy1+ dendritic epidermal
      cells--ontogenetic variation and its role in migration.

PMID- 8526034
TI  - Distribution of human colonic dendritic cells and macrophages--functional
      implications.

PMID- 8526035
TI  - Morphologic and antigenic features of dendritic cells in immune-mediated
      dermatoses: a hypothesis of differentiation.

PMID- 8526036
TI  - Tumor necrosis factor receptors of the monocyte derived Langerhans cell phenotype
      "MoLC".

PMID- 8526037
TI  - Synergistic interaction between c-kit ligand (SCF), GM-CSF and TNF promotes
      optimal dendritic Langerhans cell proliferation from primitive progenitors in
      human bone marrow.

PMID- 8526038
TI  - Expression of the high affinity receptor for immunoglobulin E (IgE) by dendritic
      cells in normals and asthmatics.

PMID- 8526039
TI  - A comparative study on Langerhans cells in lymph nodes with dermatopathic
      lymphadenopathy and histiocytosis X cells.
AB  - It was elucidated that the majority of DC were LC which were positive for CD 1a,
      but negative for PCNA, and possessed BG in the lymph nodes with DPL. On the other
      hand, HCX cells were almost always positive for PCNA. From this point of view, it
      can be speculated that LC in the lymph nodes of the DPL are non dividing mature
      cells and migrate from the skin lesion. HCX cells which were positive for CD 4
      may be more immature cells than LC in DPL, and may be pathological cells which
      can divide in the foci.

PMID- 8526040
TI  - Role of the interaction of fibronectin with epidermal Langerhans cells in
      regulating their migratory pathway.

PMID- 8526041
TI  - Expression of neuropeptides on human epidermal Langerhans cells.

PMID- 8526042
TI  - Monocyte derived dendritic cells (MODC) present phenotype and functional
      activities of Langerhans cells/dendritic cells.

PMID- 8526043
TI  - Development and distribution of T cell-associated dendritic cells in organs and
      tissues of mice depleted of blood monocytes by administration of strontium-89.

PMID- 8526044
TI  - Establishment and characterization of antigen-presenting cell lines (XS series)
      derived from newborn mouse epidermis.

PMID- 8526045
TI  - Migration of rat dendritic cells and macrophages from the peritoneal cavity to
      the parathymic lymph nodes.

PMID- 8526046
TI  - In vitro migration capacity of epidermal Langerhans cells.

PMID- 8526047
TI  - Progenitor recruitment and in vitro expansion of immunostimulatory dendritic
      cells from human CD34+ bone marrow cells by c-kit-ligand, GM-CSF, and TNF alpha.
AB  - Several cytokines have been identified that support the development of dendritic
      cells from murine and human precursor populations, most notably GM-CSF, TNF
      alpha, and IL-4. We have been interested in human bone marrow as a source of
      defined CD34+ progenitors to generate large numbers of autologous dendritic cells
      for use as adjuvants in immune based therapy. In serum-replete conditions with c
      kit-ligand, GM-CSF, and TNF alpha, dendritic cells constitute approximately 10
      15% of the myeloid progeny (equivalent to approximately 1.7 x 10(6) dendritic
      cells per single ml of starting bone marrow); and they develop together with
      granulocytic intermediates and monocytes in the same cultures. CD14- dendritic
      cells share expression of class II MHC and costimulatory ligands with CD14+
      monocyte progeny, but only the CD14- HLA-DR+ dendritic cells are highly
      stimulatory of resting unprimed T cells. We have further identified a novel
      colony that develops in the presence of GM-CSF and TNF alpha alongside typical
      CFU-GM, which is comprised of dendritic cells mixed with < or = 15% monocytes
      (CFU-DC/mono). c-kit-ligand recruits and expands early progenitors responsive to
      the dendritic cell-differentiating effects of GM-CSF and TNF alpha, effecting a
      100- to 1000-fold greater expansion of CFU-DC/mono by 14d and 21d respectively
      than does the combination of GM-CSF and TNF alpha without c-kit-ligand.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8526048
TI  - Epidermal Langerhans cell migration: signals and mechanisms.

PMID- 8526049
TI  - Population dynamics and functions of respiratory tract dendritic cells in the
      rat.

PMID- 8526050
TI  - Regulation of the humoral response by the antigen-presenting cells in vivo.

PMID- 8526051
TI  - Antigen presenting and primary in vitro sensitizing capacity of CD1a+ dendritic
      cells generated from human blood.

PMID- 8526052
TI  - Annexin expression in human dendritic cells.

PMID- 8526053
TI  - Spleen accessory cell antigen processing and in vitro induction of specific
      lymphocyte proliferation in BALB/c mice infested with nymphal Ixodes ricinus
      ticks.

PMID- 8526054
TI  - Functional dichotomy of dendritic cells isolated from blood and lymph nodes.

PMID- 8526055
TI  - Antigen processing capacity of dendritic cells from mice of different MHC
      backgrounds: down-regulation upon culture and evidence for heterogeneity of
      dendritic cell populations.

PMID- 8526056
TI  - TNF alpha interrupts antigen-presenting function of Langerhans cells by two
      mechanisms: loss of immunogenic peptides and impairment of antigen-independent T
      cell clustering.

PMID- 8526057
TI  - Thymic dendritic cells: surface phenotype, developmental origin and function.

PMID- 8526058
TI  - The role of cis-urocanic acid in UVB-induced immunosuppression.

PMID- 8526059
TI  - Antigen processing by rat lymph-borne dendritic cells.

PMID- 8526060
TI  - Evidence that Langerhans cells migrate to regional lymph nodes during
      experimental contact sensitization in dogs.

PMID- 8526061
TI  - Analysis of invariant chain processing in 3 day cultured rat Langerhans cells.

PMID- 8526062
TI  - Functional and ultrastructural aspects of antigen processing by dendritic cells.

PMID- 8526063
TI  - Processing and presentation of protein and parasite-derived antigens by 4F7+
      dendritic cells.

PMID- 8526064
TI  - Dendritic cells migrating from carcinogen-treated skin have reduced antigen
      presenting function.

PMID- 8526065
TI  - Inhibitory effects of ultraviolet B on human Langerhans cell antigen presenting
      function.

PMID- 8526066
TI  - Phenotype of cells migrated from human skin explants.

PMID- 8526067
TI  - Uptake of bead-adsorbed versus soluble antigen by bone marrow derived dendritic
      cells triggers their activation and increases their antigen presentation
      capacity.

PMID- 8526068
TI  - Ectromelia virus establishes a persistent infection in spleen dendritic cells and
      macrophages of BALB/c mice following the acute disease.

PMID- 8526069
TI  - Functional expression of ICAM-3 on human epidermal Langerhans cells.

PMID- 8526070
TI  - Multiple lines of evidence favoring a bone marrow derivation of follicular
      dendritic cells (FDCs).

PMID- 8526071
TI  - Adhesion and costimulatory molecules on human FDC in vitro.

PMID- 8526072
TI  - Architectural and antigenic features of follicular dendritic cells as a clue to
      the histogenesis of primary cutaneous B-cell lymphoma.

PMID- 8526073
TI  - An immunohistochemical study on isotypes of the immune complexes trapped by
      follicular dendritic cells (FDC) in various human lymphoid tissues.

PMID- 8526074
TI  - The interdependence of lymphocyte, stromal cell, and follicular dendritic cell
      maturation.

PMID- 8526075
TI  - The monoclonal antibody FDC-M1 recognizes possible follicular dendritic cell
      precursors in the blood and bone marrow.

PMID- 8526076
TI  - Expression of complement regulating proteins on FDC.

PMID- 8526077
TI  - Distribution and characterization of follicular dendritic cells (FDCs) in non
      Hodgkin's lymphomas.

PMID- 8526078
TI  - Follicular dendritic cells induce B cell activation.

PMID- 8526079
TI  - Germinal center T cells: analysis of their proliferative capacity.

PMID- 8526080
TI  - Iccosomes and induction of specific antibody production in vitro.

PMID- 8526081
TI  - Recombinant GM-CSF induces cytokine production in mouse dendritic cell clones.

PMID- 8526082
TI  - Localizations of regulatory proteins of complement components on RA synovial
      tissues--especially germinal centers.

PMID- 8526083
TI  - In vitro immune complex binding assay to examine the mechanism of immune complex
      trapping by human follicular dendritic cells (FDC).

PMID- 8526084
TI  - SIV infection of follicular dendritic cells (FDC) and other spleen cell subsets
      in experimentally infected cynomolgus monkeys.

PMID- 8526085
TI  - Morpho-functional changes of follicular dendritic cells (FDC) and lymph node
      structure in simian immunodeficiency virus (SIV) infection.

PMID- 8526086
TI  - Modulation of B lymphocyte proliferation inside the germinal center.

PMID- 8526087
TI  - Human follicular dendritic cells promote both proliferation and differentiation
      of CD40 activated B cells.

PMID- 8526088
TI  - Dendritic cells as stimulator cells of MHC class I-restricted immune responses.
AB  - We have shown that growth factor-dependent, MHC class I+/II dendritic cell lines
      established from mouse fetal skin, can stimulate naive, allogeneic but not
      syngeneic CD8+ T cells in the absence of CD4+ T cells and that this T cell
      response is restricted by MHC class I molecules. We further showed that the FSCL
      induced activation of naive CD8+ T cells is critically dependent on the physical
      contact between stimulator and responder cells and the expression of the
      costimulatory molecule B7 on FSCL. An important question that remains to be
      addressed concerns the derivation of FSCL. One could argue that they are members
      of the LC/DC family because they (i) exhibit certain features of fetal murine LC
      (i.e., CD45+, CD44+, CD32+, MHC class I+, MHC class II-, asialo GM1+, TCR-)
      including membrane-bound ADPase activity (A. Elbe, unpublished observation) and
      (ii) exhibit a pronounced dendritic configuration when cultured. If these cells
      are indeed derived from fetal LC, they should undergo the same phenotypic changes
      (MHC class II(-)-->MHC class II+) under in vitro culture conditions as do fetal
      LC in situ. However, our FSCL are phenotypically stable, and attempts to induce
      MHC class II expression with cytokine cocktails were unsuccessful. One
      explanation for this phenomenon could be that stimulatory signals provided by
      fetal keratinocytes or other skin cells are responsible for LC maturation in vivo
      and that, due to the early demise of these "stromal" cells in fetal skin cell
      cultures, the maturation process would not have been completed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8526089
TI  - Dendritic cells regulate development of alloantigenic and mitogenic TH1 versus
      TH2 responses.

PMID- 8526090
TI  - Review of the characteristics of six cell lines with Langerhans cell phenotype.

PMID- 8526091
TI  - New molecules on dendritic cells and their interactions with T lymphocytes.

PMID- 8526092
TI  - Phenotype and alloactivating capacity of dendritic cells generated under
      different culture conditions from human peripheral blood.

PMID- 8526093
TI  - Inhibitory effect of IL-10 on human Langerhans cell antigen presenting function.

PMID- 8526094
TI  - IL-10 inhibits the primary allogeneic T cell response to human peripheral blood
      dendritic cells.

PMID- 8526095
TI  - A molecular strategy to identify molecules that are specific for dendritic cells
      and/or critical to their unique immunostimulatory function.

PMID- 8526096
TI  - Activation of primary allogeneic CD8+ T cells by dendritic cells generated in
      vitro from CD34+ cord blood progenitor cells.

PMID- 8526097
TI  - Stimulation of human anti-viral CD8+ cytolytic T lymphocytes by dendritic cells.

PMID- 8526098
TI  - T-lymphocyte proliferation stimulated by alpha beta TCR/CD2 bispecific antibody
      is dependent on LFA-1/ICAM-1 recognition of accessory cells.

PMID- 8526099
TI  - Low reactivity of peripheral blood dendritic cells respond to IL-1 and GM-CSF in
      SLE patients.

PMID- 8526100
TI  - Defect of the CTLA4-Ig ligands on tumor-infiltrating dendritic cells.

PMID- 8526101
TI  - Immortalized murine dendritic cells: phenotypic and functional characterization.

PMID- 8526102
TI  - Mixed epidermal cell lymphocyte reaction: HLA-DR+ cells exhibit a greater
      immunostimulatory activity than CD1a+ cells.

PMID- 8526103
TI  - Human dendritic cells enhance growth and differentiation of CD40 activated B
      cells.

PMID- 8526104
TI  - Human dendritic cells can drive CD40-activated sIgD+ B cells to mount mucosal
      type humoral response.

PMID- 8526105
TI  - Factors affecting spontaneous dendritic cell-lymphocyte clustering in skin
      afferent lymph.

PMID- 8526106
TI  - Characteristics of antigen-independent and antigen-dependent interaction of
      dendritic cells with CD4+ T cells.

PMID- 8526107
TI  - Priming of T cells with dendritic, macrophage and B cell lines in vivo requires
      more than surface expression of MHC II and B7 molecules--possible role of CD44
      and integrins.

PMID- 8526108
TI  - Identification of novel cDNAs derived from human lung dendritic cells using a
      subtractive cloning approach.

PMID- 8526109
TI  - Mechanisms of retrovirally induced immunosuppression acting via dendritic cells.

PMID- 8526110
TI  - Preferential entry and productive infection of CD4 expressing lymphoid dendritic
      cells by macrophage-tropic HIV-1.

PMID- 8526111
TI  - Production and properties of large numbers of dendritic cells from human blood.

PMID- 8526112
TI  - Expression of cytokine mRNA by human peripheral blood dendritic cells stimulated
      with human immunodeficiency virus and herpes simplex virus.

PMID- 8526113
TI  - Splenic interdigitating dendritic cells in humans: characterization and HIV
      infection frequency in vivo.

PMID- 8526114
TI  - HIV infection of blood dendritic cells in vitro and in vivo.

PMID- 8526115
TI  - In vivo and in vitro infection of human Langerhans cells by HIV-1.

PMID- 8526116
TI  - In vitro infection of human epidermal Langerhans cells with human
      immunodeficiency virus type 1.

PMID- 8526117
TI  - Dendritic cell-T cell conjugates that migrate from normal human skin are an
      explosive site of infection for HIV-1.

PMID- 8526118
TI  - Cell-cell interactions regulate dendritic cell-dependent HIV-1 production in CD4+
      T lymphocytes.
AB  - We investigated the role of blood dendritic cells (DC) in transmission of HIV-1
      from infected to uninfected CD4+ T cells, and the accessory molecules involved.
      DC promoted transmission from infected to uninfected CD4+ cells, but blood DC
      themselves were not infectable. DC-mediated transmission was blocked by mAb to
      CD4 and MHC class II, but strongly increased by mAb to CD40 on DC or CD28 on T
      cells. The DC-dependent infection was inhibitable by anti-CD80 and a soluble
      fusion protein of the CD80 ligand, CTLA4; soluble CTLA4Ig also blocked infection
      augmented by crosslinking CD40. We also demonstrated that mAb to CD40 up-regulate
      the expression of CTLA4 ligands CD80 and B70/B7-2 (CD86) on DC. These data
      suggest that the dialog between CD40-CD40 ligand (CD40L) and CD28-CD80 counter
      receptors on DC and T cells may be linked to HIV infection in vivo.

PMID- 8526119
TI  - In vitro HIV-1 infection of isolated epidermal Langerhans cells with a cell-free
      system.

PMID- 8526120
TI  - Defects in the function of dendritic cells in murine retroviral infection.

PMID- 8526121
TI  - Human epidermal Langerhans cells efficiently present HIV-1 antigens to specific T
      cell lines.

PMID- 8526122
TI  - Infection of cultured immature dendritic cells with human immunodeficiency virus
      type 1.
AB  - An in vitro culture system was developed that facilitates detailed studies of the
      interaction of Human Immunodeficiency Virus (HIV) with dendritic cells (DC).
      Cultured immature DC were generated from adherent peripheral blood mononuclear
      cells in the presence of GM-CSF and IL-4. These cells were non-adherent, non
      phagocytic and had a veiled surface appearance. They expressed high levels of MHC
      class I and II proteins, CD1a, B7/BB1 and low levels of CD4, and were known to
      possess a potent soluble antigen presenting capacity. Upon infection with the HIV
      1 strains Lai (lymphocytotropic) and BaL (monocytotropic), the viral RNA was
      reverse transcribed to complete DNA provirus. However the infection was non
      productive as judged from measuring the activity of the virus encoded reverse
      transcriptase in the culture supernatant. Thus HIV infection was restricted at a
      step post entry.

PMID- 8526123
TI  - Discontinuous distribution of HIV-1 quasispecies in epidermal Langerhans cells of
      an AIDS patient and evidence for double infection.

PMID- 8526124
TI  - Conditional ablation of dendritic cells in mice: comparison of two animal models.

PMID- 8526125
TI  - Activation of an HIV-LTR-CAT transgene in murine macrophages by interferon-gamma
      in synergism with other cytokines or endotoxin.

PMID- 8526126
TI  - Dendritic cells, apoptosis and murine retrovirus.

PMID- 8526127
TI  - Early events in contact sensitivity.

PMID- 8526128
TI  - Dendritic cells can be used as physiological adjuvant in vivo.

PMID- 8526129
TI  - Dendritic cells seclude Leishmania parasites that persist in cured mice--a role
      in the maintenance of T-cell memory?

PMID- 8526130
TI  - Exposure to type-I collagen induces maturation of mouse liver dendritic cell
      progenitors.

PMID- 8526131
TI  - Human keratinocyte-derived IL-12 affects LC-induced allogeneic T-cell responses.

PMID- 8526132
TI  - Studies on Langerhans cell phenotype in human afferent skin lymph from allergic
      contact dermatitis.

PMID- 8526133
TI  - Rosettes of Langerhans cells and activated T cells in human skin lymph derived
      from irritant contact dermatitis.

PMID- 8526134
TI  - A simplified method for growing dendritic cells from rat bone marrow.

PMID- 8526135
TI  - Migration of interleukin-6 producing Langerhans cells to draining lymph nodes
      following skin sensitization.

PMID- 8526136
TI  - The role of cytokines in the pathogenesis of pulmonary Langerhans' cell
      histiocytosis.

PMID- 8526137
TI  - Importance of HLA-DR+ and CD1a+ epidermal cells for cytokine production in
      psoriasis.

PMID- 8526138
TI  - Isolation of dendritic leukocytes from mouse liver.

PMID- 8526139
TI  - Electronmicroscopic study of canine cutaneous histiocytoma: a benign Langerhans
      cell tumor.

PMID- 8526140
TI  - Isolation and characteristics of dendritic cell progenitors from the bone marrow
      of the Hodgkin's disease patients.

PMID- 8526141
TI  - Defective dendritic cell (DC) function in a HLA-B27 transgenic rat model of
      spondyloarthropathy (SpA).

PMID- 8526142
TI  - Improved isolation of dendritic cells in chronic arthritic joints reveals no B7
      (CD80) surface expression.

PMID- 8526143
TI  - Vaccine adjuvancy: a new potential area of development for GM-CSF.

PMID- 8526144
TI  - Transition of T3-induced monocyte-derived veiled/dendritic cells into macrophage
      like cells by lipopolysaccharide.

PMID- 8526145
TI  - Immunophenotypical and functional characterization of bone marrow derived
      dendritic cells.

PMID- 8526146
TI  - Expression of B7 costimulator molecules on mouse dendritic cells.
AB  - Dendritic cells express most known accessory molecules [ICAM's, LFA's, B7's, and
      CD40] for binding and stimulating T cells. B7 is the most abundant of these, and
      B7-2 very much predominates relative to B7-1. B7 expression is regulated, not by
      LPS, but by some signal [s] that parallels maturation. B7 contributes to the T
      cell stimulatory function of dendritic cells, as do the other accessory
      molecules. B7-2 is expressed on dendritic cells and macrophages at several sites
      in situ, especially dendritic cells in the T cell areas.

PMID- 8526147
TI  - Stem cell factor enhances dendritic cell development.

PMID- 8526148
TI  - Development of rat DC by in vitro culture of bone marrow cells.

PMID- 8526149
TI  - Dendritic cells differentiated from human monocytes through a combination of IL
      4, GM-CSF and IFN-gamma exhibit phenotype and function of blood dendritic cells.
AB  - Our previous studies demonstrated that monocytes, when cultured under certain
      conditions, are able to differentiate into DC-like cells (MoDC) presenting a high
      accessory activity and low phagocytic function. In the present study, we
      demonstrate that under the effect of a triple combination of IL-4, IFN-gamma and
      GM-CSF human blood monocytes are able to differentiate into the cells expressing
      an identical phenotype and functional features of blood dendritic cells. MoDC
      stimulated T cell proliferation 20-30 times higher than untreated monocytes,
      similar to blood DC. They expressed abundant HLA-DR molecules, but only trace
      amounts of the monocyte/macrophage markers CD16 (FcR III), CD32 (FcR II), and
      CD14. Phagocytosis of Ig- and complement-opsonized bacteria was reduced by 93%.

PMID- 8526150
TI  - Functional CD40 antigen on B cells, dendritic cells and fibroblasts.

PMID- 8526151
TI  - Characterization of human blood dendritic cells: cytokine profiles.

PMID- 8526152
TI  - Purification of human lung dendritic cells by three color flow cytometry.

PMID- 8526153
TI  - Identification of a novel cell surface protein expressed by murine epidermal
      Langerhans cells and some lymphoid dendritic cells.

PMID- 8526154
TI  - Characterisation of adhesion molecules on the surface of dendritic cells isolated
      from human blood.

PMID- 8526155
TI  - "Whither goest lipoplasty?" or "go, or wither".

PMID- 8526156
TI  - Neurosensory preservation in endoscopic forehead plasty.
AB  - The recent introduction of endoscopic techniques and instrumentation in aesthetic
      surgery was caused in part by the desire to minimize surgical scars as well as to
      decrease the possibility of sensory changes secondary to extended incisions, such
      as the execution of a coronal incision in performing a forehead plasty. Although
      endoscopic surgical techniques provide field magnification together with
      excellent illumination, localization and preservation of the forehead
      neurovascular bundles via the endoscope can be time consuming and tedious. A new
      method is introduced where percutaneous localization of the supraorbital and
      supratrochlear nerves enables the surgeon to perform an endoscopic forehead
      plasty in an expeditious manner with preservation of sensation of the forehead
      and scalp.

PMID- 8526157
TI  - The trifurcated SMAS flap: three-part segmentation of the conventional flap for
      improved results in the midface, cheek, and neck.
AB  - While SMAS surgery revolutionized facelift procedures, the single flap created by
      conventional dissections suffers the drawback that it can only be advanced in one
      direction and sutured in place under uniform tension. Division of the flap into
      three segments overcomes this problem and allows independent pull to be applied
      in different directions to the upper midface, cheek, and neck.

PMID- 8526158
TI  - Long-term survival of fat transplants: controlled demonstrations.
AB  - To document the amount and rate of re-absorption of fatty tissue transplanted
      using the author's technique, the author initiated controlled studies in 1987. A
      selected crease was infiltrated with autologous fatty tissue using a nearby
      crease as control. At specific time intervals the infiltrated crease was compared
      to the nearby control crease to evaluate percentage of recurrence. Photographs
      were taken in the first week, then at least yearly over six years. All views, all
      positions of the mouth, and all lighting situations demonstrated the continued
      absence of any crease in the area of infiltration. In contrast, the nearby
      control crease remained unchanged or deepened from its preoperative condition,
      giving every indication of a permanent correction. This experiment demonstrates
      the potential lasting nature of corrections performed with the transplantation of
      fatty tissue and is supported by over 400 infiltrations into the nasolabial folds
      in the author's practice.

PMID- 8526159
TI  - Liposuction fat-fillant implant for breast augmentation and reconstruction.
AB  - The perfect breast implant fillant material would have higher viscosity than
      water and would be autologous and harmless. We describe the confinement of
      liposuction fat in implants using the Lipovacutainer during a routine liposuction
      procedure. This collected fat is prepared inside the Lipovacutainer and is
      reinjected through a Lipomedia filling cannula into a leaf valve implant as the
      fillant in place of saline. The implants are used for bilateral augmentation
      mammoplasty and breast reconstruction procedures. Our six clinical cases have
      been monitored closely using mammography and MRI. These cases showed slow
      liquefaction without interference with mammography studies. We obtained excellent
      overall body contours. All complications were correctable and non-life
      threatening and there was no capsule formation.

PMID- 8526160
TI  - Prominent ears and their correction: a forty-year experience.
AB  - The technique described in this article correcting the protruding ear deformity
      has evolved over 40 years. The original procedures and our subsequent
      modifications are described, including 20-year followup results. The possible
      pitfalls in carrying out this procedure and how to avoid them are also described.
      A relatively standardized short procedure with minimal morbidity and maximum long
      term results yields an aesthetically satisfactory looking ear.

PMID- 8526161
TI  - HTR polymer facial implants: a five-year clinical experience.
AB  - Forty-three patients at two different international sites underwent onlay facial
      augmentation of the malar, paranasal, and chin regions using 61 HTR polymer
      preformed implants. All implants were placed intraorally and rigidly fixed with a
      titanium screw. Over postoperative periods ranging from two to five years, one
      implant was removed because of infection. Two other implants in patients with
      rheumatic and connective tissue disease were removed because of persistent pain
      and erythema. Another peri-implant infection was treated successfully without
      removal. One-year postoperative radiographs in patients with chin implants
      demonstrated no underlying bone resorption. This porous polymeric material
      appears to offer clinical results comparable to other alloplastic materials for
      onlay facial skeletal augmentation.

PMID- 8526162
TI  - Nose surgery and the vomeronasal organ.
AB  - The latest reports on the anatomical and functional characteristics of the
      vomeronasal organ (VNO) are evaluated. The high incidence of identification of
      the vomeronasal organ in normal individuals indicates that the vomeronasal organ
      in normal individuals indicates that the vomeronasal system is a universal
      feature of the adult human nasal cavity. Evaluation of the neuronal connections
      between this organ and the central nervous system shows that the VNO is a
      functional chemosensory system with sexually dimorphic specificity and the
      ability to transduce signals that modulate certain autonomic parameters. The
      presence of the VNO and its clinical significance must be considered by plastic
      surgeons during nasal operations.

PMID- 8526163
TI  - Management of the septum during rhinoplasty.
AB  - Septal deviation is the rule more than the exception in most cases of
      rhinoplasty. When deviation of the septum precludes a good rhinoplasty's
      functional and aesthetic results because of impairment of nasal air flow,
      residual deviation, or inadequate medialitation of the lateral nasal wall, a
      modified submucous resection of the deviated part is certainly indicated. If
      possible, a dorsocaudal L-strut of cartilage should be maintained, but, if
      necessary, it can be resected partially or totally and the support of this area
      reestablished by dorsal and columellar cartilage grafts. The authors recommend a
      bilateral mucoperichondrial-mucoperiosteal dissection of the septum from its
      caudal edge to the most posterior deviated part, because it provides easy septal
      resection in a good surgical field.

PMID- 8526164
TI  - Forehead rhytidoplasty: endoscopic approach.
AB  - The difficulty in determining how much skin must be resected to achieve an
      adequate forehead and eyebrow lift through the coronal approach led the author to
      search for another forehead rhytidoplasty procedure. The endoscopic approach
      yields a natural lift of the eyebrows without skin excision through a minimal
      incision. It has been useful for patients who have a prominent forehead or have
      had a forehead rhytidoplasty. In addition, this technique provides a smooth
      forehead that is achieved by breaking the continuity of the forehead and glabella
      muscles. Despite the fact that the endoscopic approach is in the early stages of
      development, the results obtained from its use allow it to be an alternative
      procedure for treating the aging forehead and glabella.

PMID- 8526165
TI  - The occipito-parietal flap method in the treatment of male baldness.
AB  - Which hair transplant technique to use for correcting male baldness is decided on
      by the type of baldness, the condition and direction of the donor's hair, and the
      favored hairstyle. In the occipital-parietal flap technique presented here, a
      flap is raised on one side of the occipital part. The flap is 4 cm wide and
      stretches toward the lower part of the parietal. After a week's delay, the flap
      is transplanted from the top of the head to the frontal part under general
      anesthesia. Light pressure is applied to the transferred flap with a tie-over
      dressing. With this technique the hair grows downward and covers both the front
      and top parts of the head. It is important to choose a case for which this type
      of procedure is appropriate. The authors' technique can be applied to types IV,
      V, and Va of Norwood's classification.

PMID- 8526166
TI  - Twelve years' experience of calf augmentation.
AB  - The author describes his 12 years' experience of performing calf augmentation
      using gel-filled implants for the correction of thin or asymmetrical legs. In
      essence, these implants are placed over the gastrocnemius muscle beneath the
      fascia cruris.

PMID- 8526167
TI  - Investigation on the efficacy and tolerance of azelastine (HCL) nasal spray
      versus ebastine tablets in patients with seasonal allergic rhinitis.
AB  - We compared the efficacy and tolerance of Azelastine nasal spray (0.14 mg in each
      nostril twice a day) versus Ebastine tablets (10 mg) as a single night dose in a
      Phase IV open, randomized, parallel-group clinical trial lasting 14 days,
      conducted with 63 patients diagnosed of seasonal allergic rhinitis. The symptoms
      assessed before and after the treatment period were: sneezing, nasal pruritus,
      rhinorrhea, nasal obstruction, conjunctival erythema, eye pruritus, eye watering,
      photophobia, pharyngeal pruritus and cough. Each symptom was rated by the
      patients according to a 4-point scale: absent: 0, mild: 1, moderate: 2, and
      severe: 3. The score required to be included in the study was 8 or above. In
      addition, the resistance of nasal fossae was assessed, before and after the
      treatment, by active anterior rhinomanometry, as well as the appearance of
      adverse events. Both drugs were equally effective both in the control of symptoms
      and in decreasing the airway resistance and no statistically significant
      differences were observed in the variables tested in both groups. We concluded
      that Azelastine nasal spray is a treatment as effective as Ebastine in the relief
      of symptoms of seasonal allergic rhinitis, with an excellent tolerance and
      minimum adverse effects.

PMID- 8526168
TI  - A double-blind, placebo controlled study of Alpare mite D. pteronyssinus
      immunotherapy in asthmatic patients.
AB  - Results from one immunotherapy study can be difficult to extrapolate when
      physicians use products or dose schedules that differ from the ones used in that
      particular study. The purpose of this study was to determine if an alum absorbed
      Alpare D. pteronyssinus extract administered in a maintenance dose of 10,000
      12,500 BU's could be shown to improve symptoms in asthmatic patients allergic to
      D. pteronyssinus. Previous studies using higher doses of extracts suggested
      efficacy but frequent side effects were noted. A double blind placebo controlled
      study was performed which included 24 active and 25 placebo patients. We measured
      skin reactivity, methacholine challenge changes, symptoms by visual analog score,
      specific IgE levels, and end of study assessment. The results showed
      significantly greater improvement in actively treated patients versus those given
      placebo in specific IgE levels, symptoms by visual analog score, and end of study
      status. We saw no significant differences in skin reactivity, methacholine
      challenge, or diary medication scores. In addition, no difference in side effects
      was noted between the two groups. We conclude that the dose administered in this
      study was safe and well tolerated. Some clinical improvement did seem to occur
      but the study suggests that higher doses may be indicted in certain patients.

PMID- 8526169
TI  - Contact dermatitis: clinical review of 800 patients tested using the standard
      European series.
AB  - The results of the use of the European Standard Series on 800 patients suffering
      from Contact Dermatitis, including occupational Dermatosis is reported. This work
      also attempts to provide insight into the interests and difficulties of carrying
      out an epidemiological study in an Allergy Centre and Immunology Clinic. All the
      patients underwent a Patch Test following the guidelines laid out by the
      International Contact Dermatitis Research Group. The results of the patch tests
      were positive in 462 patients (57.7%) and negative in 338 cases (42.3%). The
      agents responsible for the symptoms in our study were as follows: metals (33%),
      parafenilen-diamine (13.9%), cobalt (13.3%), perfumes (5.5%), benzocaine (5.4%)
      and potassium dichromate (5.4%). In this study 72 patients were verified to have
      Occupational Dermatosis, corresponding mainly to the following occupational
      sectors: metal industry workers, hairdressers and bakers and pastry makers.

PMID- 8526170
TI  - A double-blind, randomized study investigating the efficacy and specificity of
      immunotherapy with Artemisia vulgaris or Phleum pratense/betula verrucosa.
AB  - This study investigated the specificity and efficacy of immunotherapy with
      Artemisia vulgaris (Artemisia) extract. We studied 25 patients with a more than
      two year lasting history of seasonal rhinoconjunctivitis and who had only two
      clinically important allergies, either to Artemisia and Betula verrucosa (Betula)
      or to Artemisia and Phleum pratense (Phleum). Patient selection was randomized
      and evaluation of results was conducted in double blind fashion. Twenty patients
      completed two years of specific immunotherapy. Nine patients were treated with
      extracts of Artemisia and 11 with extracts of either Betula (n = 3) or Phleum (n
      = 8). Treatment with Artemisia was followed by a significant decrease in skin
      sensitivity (p < 0.05) and eye sensitivity (p < 0.01) to Artemisia but not to
      Betula/phleum. No significant decrease was observed in medicine consumption or
      symptom scores. Patients treated with Betula or Phleum experienced a significant
      decrease in skin sensitivity to Betula or Phleum (p < 0.001), and eye sensitivity
      to Betula or Phleum (p < 0.05), but not to Artemisia and had significant
      decreases in medicine and symptom scores (p < 0.05) in Betula/phleum seasons but
      not in the Artemisia season. The treatment was both effective and specific with
      the one unexplained exception that both patient groups (Artemisia and
      Betula/Phleum) decreased their skin sensitivity to Artemisia.

PMID- 8526171
TI  - Investigation of acid phosphatase as a possible IgE-binding marker for pollen
      allergens and their polymerized derivatives.
AB  - The enzyme acid phosphatase represents an important component among the
      allergenic proteins in most pollen extracts. However, determination of the level
      of this enzyme in extracts of various pollen species, as well as protein
      separation by molecular sieving shows that acid phosphatase cannot be used as a
      marker for IgE-binding protein allergens. A conspicuous discrepancy was observed
      between the heat- and acid-sensitivities of the phosphatase enzyme relative to
      the overall IgE-binding properties of the pollen extracts. Remarkably, the enzyme
      remained unaffected by cross-linking the pollen proteins with glutardialdehyde,
      whereas this process of polymerization caused the IgE-binding potency to diminish
      considerably. It is concluded that the enzyme acid phosphatase is not a suitable
      marker for the potency assessment of pollen allergens, but may be useful for
      monitoring the production process of polymerized allergoids.

PMID- 8526172
TI  - [Diagnosis of allergic rhinitis].

PMID- 8526173
TI  - [Anaphylaxis caused by human seminal fluid].
AB  - Anaphylaxis to human seminal fluid (HSF) is rare. We present an atopic woman with
      postcoital cutaneous and respiratory symptoms. Prick by prick to HSF was
      positive. CAP to FSH was also positive (4 KU/l). The clinical findings,
      differential diagnosis and different treatments are discussed.

PMID- 8526174
TI  - Birch pollen related food hypersensitivity: as a para-occupational syndrome.
AB  - Two patients presented with allergy to birch pollen and hypersensitivity to
      hazelnut and apple. Since both of these patients developed pollen sensitivity
      when they were abroad for occupational purpose, we want to mention this situation
      as "a para-occupational syndrome".

PMID- 8526175
TI  - Pseudoasthma in a case of asthma.
AB  - The respiratory system, which is composed of the upper and lower airways performs
      varied and distinct functions. These can also be the sites of various
      pathological processes. Asthma is one of the major conditions involving the lower
      airways whereas laryngeal dysfunction due to various conditions has also been
      known to occur. Isolated laryngeal dysfunction with abnormal vocal cord movements
      has been shown to occur both in various organic and non-organic conditions. The
      non-organic laryngeal dysfunction with a functional component is being
      increasingly recognized, the symptoms of which can be easily confused with those
      of asthma. We describe a patient who is believed to have both asthma and
      functional laryngeal dysfunction with paradoxical motion of the vocal cords on
      inspiration, observed on direct laryngoscopy. It is also believed that her
      laryngeal dysfunction is an isolated clinical entity not related to her
      underlying asthma, which has been shown, at times, to be associated with non
      compensatory adduction of the vocal cords on inspiration. The patient described
      is known to have an anxious and hysterical personality and was also diagnosed to
      have a major depression. Episodes of paradoxical motion of the vocal cords on
      inspiration are acute and are usually precipitated by an emotional event and the
      shortness of breath may or may not be associated with stridor. Treatment of this
      condition, which can be mistaken for asthma, involves speech/vocal cord exercises
      to be used at the advent of an attack. It is thus important to recognize this
      condition so that appropriate treatment can be given.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8526176
TI  - [Comparative study] of beclomethasone and budesonide, with same posology (400
      micrograms every 12 hours), in the control of cortico-dependent intrinsic
      asthma].
AB  - Inhaled steroids have rendered an undoubtful benefit in the control of airway
      inflammation of the asthmatic patients. Our objective was to compare clinical
      efficacy between budesonide (BUD) and beclomethasona depropionate (BDP), when
      administered at equal doses (800 micrograms/24 hours). A two ways crossed open
      clinical trial was designed. Thirty-three steroid dependent chronic asthmatic
      patients (18 females, 15 males) were included. Ages ranged from 29 to 73 years
      (mean = 52.5 +/- 11.7). All subjects suffered a severe asthma, with several years
      of activity (mean = 11.7 +/- 7.8), insufficiently controlled by inhaled steroids
      and bronchodilators, who required regular systemic steroids supply. The
      parameters compared were: the patients subjective symptoms punctuation (cough,
      expectoration, thoracic noises, exercise induce dyspnea and dyspnea at rest),
      salbutamol needs (number of inhalations/day), additional prednisone needs, sputum
      eosinophil counts, FEV1 measurement and inespecific bronchial reactivity control
      (PD20 methacoline). After a baseline week patients received one of the drugs for
      6 weeks and, after a lavage week, the other drug was administered for another 6
      weeks. All patients improved with both therapies. We got the following
      conclusions: 1) a significative decrease in salbutamol (p < 0.05-0.001) and
      prednisone needs (p < 0.05-0.001); 2) this decrease has been more important
      during BUD therapy, although without significative differences; 3) no significant
      variations in sputum eosinophils, FEV1 or bronchial reactivity were observed; 4)
      both drugs, when administered at equal doses, have probed to be equally effective
      in severe steroid dependent asthma control.

PMID- 8526177
TI  - Cyclosporin in steroid dependent asthma.
AB  - Cyclosporin A(CsA) is an immunosupressive drug which inhibits predominantly T
      lymphocyte dependent immune responses. In recent years, CsA is reported to have
      significant steroid sparing effect in severe asthma. We used CsA top treat 12
      steroid dependent asthmatic patients who had been on systemic steroids for an
      average of 8.5 years. During the baseline period lasting 3 months, therapy was
      standardized with inhaled beclamethasone, salbutamol and aminophylline and
      minimal necessary dose of steroid for each patient was determined. Treatment
      period lasted three months with 3 mg/kg/day CsA orally, the mean CsA whole blood
      level through the study was 77.25 ng/ml. In patients the daily dose of prednisone
      could be reduced from mean 31.43 mg to mean 8.57 mg (p < 0.01), while an average
      34% improvement was observed in FEV1 values. However in one patient attempts to
      taper steroid doses were unsuccessful. Four patients were withdrawn from the
      study due to side effects of CsA. We suggest that CsA in steroid dependent severe
      asthma can reduce the requirement for systemic corticosteroids, however side
      effects of the drug must be weighed against its possible benefits.

PMID- 8526178
TI  - [Milk microaspiration as a cause of recurrent bronchial obstruction in infants].
AB  - The presence of Lipid-Laden alveolar macrophages (L.L.M.) obtained by pharyngeal
      aspiration an stained by a modification of the Papanicolau staining procedure as
      prospectively evaluated in populations of milk-fed infants, under one year old,
      with a history of two or more episodes of obstructive bronchitis (n = 53), and
      compared to 29 control infants. Twenty-one infants (39%) with a past history of
      recurrent bronchitis were positive for the presence of LLM. The absence of LLM in
      29 control infants suggest that the aspiration may be one cause of recurrent
      bronchitis in infants.

PMID- 8526179
TI  - Immunotherapy with the storage mite lepidoglyphus destructor.
AB  - We carried out a double-blind clinical trial of immunotherapy on 35 patients
      sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12
      months of specific hyposensitization (Abello Lab., Spain) we performed in vivo
      (skin tests with Ld, methacholine and challenge tests), and in vitro tests
      (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to
      their major allergen Lep dI). We also monitored the efficacy and safety of the
      immunotherapy with clinical and analytical controls (symptoms and medication
      score, detection of immune complexes). After therapy we found a significant
      decrease in specific skin reactivity, dose of positive challenge tests, and
      hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE
      to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to
      Ld and Lep DI. The placebo group showed no changes in these variables. There were
      no severe secondary reactions after treatment with the extract. Patients-self
      evaluation was favourable and their labour absence decreased. No development of
      circulating immune complexes was associated with this immunotherapy.

PMID- 8526180
TI  - Safety and efficacy of sublingual rush immunotherapy with grass allergen
      extracts. A double blind study.
AB  - Thirty-four patients suffering from rhinoconjunctivitis with or without asthma
      due to grass pollen, were submitted to sublingual immunotherapy according to a
      double blind placebo controlled experimental plan; eighteen patients received the
      active therapy, sixteen the placebo. A rush preseasonal treatment schedule was
      followed in order to reach the maintenance dose in 15 days with two
      administrations per day; the top dose reached was then administered three times a
      week until the end of the pollen season. The symptoms and drugs related to
      rhinoconjunctivitis and asthma were recorded by means of diary cards and grass
      pollen counts were performed during the season. The actively treated group showed
      a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of
      drugs for the same symptoms; all these differences resulted to be statistically
      significant. No patient showed local or systemic side effects of any relevance.
      According to these results of our study, sublingual rush immunotherapy is
      clinically effective and because of the ease of handling, the shortness of the
      treatment, the absence of relevant side effects and the high compliance of the
      patient can be considered as an alternative to classic injective immunotherapy in
      grass pollen allergic patients.

PMID- 8526181
TI  - [Relative humidity and acari. An intervention study].
AB  - In this work we collect the results of the variation of the variable "rechange of
      the wind with the exterior" in the three possibilities of a bedroom: --close
      window, semi close and totally open. And we unite the relation that we already
      know between the prevail of acariens (Dermatophagoides) and the relative humidity
      of the wind in a Bilbao city's house.

PMID- 8526182
TI  - Risk factors for asthmatic patients requiring intubation: A comprehensive review.
AB  - During recent decades, asthma prevalence and mortality have increased at rapid
      rats worldwide among children, teenagers, and young adults. The increased
      mortality of patients with asthma have mounted significant concerns. Indeed the
      paradox of improved pharmacotherapy but worsening prognosis has been explored in
      depth in several studies including observations in epidemiology, access to
      medical cared and drug toxicity. In the United States, the asthma mortality rate
      has increased steadily over the past fifteen years and has only recently shown
      signs of leveling off. It is widely believed, although unproven that many asthma
      deaths may be preventable. We have addressed one critical factor in severe asthma
      by attempting a definition of risk factor for intubation using demographic data
      and a retrospective cohort study of hospitalized asthmatics. This study included
      all asthmatics aged 5 through 34 years admitted over a 10-year period (1984-1994)
      to the University of California Davis Medical Center. Nine hundred ninety three
      such asthma admissions were reviewed, involving 556 females and 437 males, mean
      age of 19.7 years. Of this group, 284 were White, 459 were Black, 182 were
      Hispanic, 40 were Asian and 28 were American Indian. By National Heart, Lung, and
      Blood Institute guidelines, there were 284 mild, 524 moderate and 185 severe
      cases. Fifty seven asthmatics required intubation for their asthma. The
      significant risk factors identified for intubation were psychological and
      psychosocial problems, family dysfunction, low socioeconomic status, little
      formal education, unemployment, active tobacco smoking and/or second hand smoke
      exposure, parenteral history of allergy or asthma, atopy, prior intubation,
      intercurrent respiratory infection, language barrier, crowding, prior asthma
      emergency room visit in past year, prior asthma hospitalization in past year, and
      steroid dependence. These risk parameters may be important determinants of
      baseline risk for asthma deaths and their recognition may have a significant
      impact on preventive measures.

PMID- 8526183
TI  - [Transversal myelitis as initial manifestation of secondary antiphospholipid
      syndrome. Report of a case].
AB  - We report the clinical case of an 8 years female with systemic lupus
      erythematosous who developed transverse myelitis secondary to antiphospholipid
      syndrome. She had an excellent response to the treatment with Prednisone and
      Cyclophosphamide. As long as we know this is the first report of transverse
      myelitis as clinical manifestation of antiphospholipid syndrome in childhood.

PMID- 8526184
TI  - [Type III polyglandular autoimmune syndrome. Report of a case].
AB  - Type III polyglandular syndrome is defines as the association of insulin
      dependent Diabetes mellitus, thyroid gland affection (hyper or hypothyroidism)
      and a non endocrinological disease, rheumatological or not. Less common
      manifestations include pernicious anemia, vitiligo and alopecia. Circulating
      organ-specific auto antibodies are detected in blood smear and a lymphocyte
      infiltrate in the affected glands. We report a patient with insulin dependent
      Diabetes mellitus since the age of 3, who developed hypothyroidism at the age of
      14 and severe rheumatoid arthritis at 16. Moderate anemia with positive auto
      antibodies against parital gastric cells was detected. Treatment with
      methotrexate and indomethacin was indicated with excellent results regarding her
      arthritis and after 2 weeks of treatment she began to walk normally again.

PMID- 8526185
TI  - Optimal number of chemotherapy courses in advanced nonseminomatous testicular
      carcinoma.
AB  - BACKGROUND: Nonseminomatous germ cell tumors (NSGCT) (testicular carcinoma) are a
      curable disease. Stages I and II are nearly 100% curable. Stage III has had
      remarkable progress in attaining complete regression, but a substantial number
      fail to be cured. Using platinum-based regimens such as vinblastine, bleomycin,
      and cisplatin (VBP), or using etoposide instead of vinblastine (BEP), or without
      bleomycin (EP), four courses of chemotherapy have become a national standard.
      Based on our prior experience with mithramycin (plicamycin), which used six
      courses, six courses of VBP chemotherapy were utilized as our treatment goal.
      This report challenges the concept that "standard therapy" for stage III
      testicular carcinoma is four courses. METHOD: From 1976 to 1990, 74 patients with
      advanced NSGCT were treated with standard doses of plantinum-based
      chemotherapies. Five or more courses were delivered to 41 patients and fewer than
      five courses to 33 patients. The intent of therapy was to attain as close to six
      courses as possible. Because of physician preference, patient adherence, or
      toxicity, some patients did not reach that goal. RESULTS: Of 33 patients
      receiving less than five courses, there were 28 (85%) complete responders, and 26
      (78.8%) are alive. Of 41 patients receiving five or more courses, 38 (92.7%) had
      complete responses, and 34 (83%) are alive. One person in each group is living
      with nonresectable teratoma present. In the group receiving 5+ courses, two died
      from causes unrelated to testis cancer and had no testis cancer present. As a
      result of the initial treatment, there was no evidence of cancer in 24 (72.8%) in
      the group receiving less than five courses and 35 (85.4%) had no cancer after
      five or more courses. In considering only patients with advanced level of stage
      III disease in contrast to minimal or moderate stage III disease, there were
      fewer complete regressions with less than five courses (64.3%) than with five or
      more courses (88.0%). CONCLUSIONS: For minimal stage III disease, four courses of
      chemotherapy may be adequate. For advanced stage III disease, more chemotherapy
      provides fewer treatment failures. Once a complete response is achieved without
      restriction to an arbitrary number of courses, two additional courses may
      constitute a more curative regimen.

PMID- 8526186
TI  - Increased incidence of central venous catheter-related infections in bone marrow
      transplant patients.
AB  - In view of an apparent increase of central venous catheter-related infections
      among our bone marrow transplant (BMT) patients, a retrospective study of
      infectious complications of central venous catheters was conducted. During 1992,
      147 central venous catheters were placed in 133 patients. The overall infection
      rate of all catheters was 3.3 per thousand catheter-days (bacteremia 1.8, site
      infection 1.5). Patients scheduled for BMT had the highest infection rate of 11.5
      (bacteremia 6.7, site infection 4.8). HIV patients had an infection rate of 6.6
      per thousand catheter-days (bacteremia 3.8 and site infection 2.8) and patients
      with other diagnoses had a rate of 2.4 (bacteremia 1.3 and site infection 1.1).
      The difference of infection risk among the three groups is statistically
      significant (logrank p < .0001). In analyzing the 11 BMT patients more carefully,
      14 catheters were placed. Of these, 9 catheters were removed, 8 (89%) of which
      were secondary to infection. Multivariate analysis showed that patients under 50
      and BMT patients were more likely to develop catheter-related infection. While
      the cause of this complication is not known at present, the possible association
      with PBSC harvest is of much concern.

PMID- 8526187
TI  - Phase III study comparing vincristine, doxorubicin (Adriamycin), and
      dexamethasone (VAD) chemotherapy with VAD plus recombinant interferon alfa-2 in
      refractory or relapsed multiple myeloma. An Eastern Cooperative Oncology Group
      study.
AB  - PURPOSE: This clinical trial was designed to compare the effectiveness of
      vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) with VAD plus
      interferon alfa-2 in patients with refractory or relapsed multiple myeloma.
      PATIENTS AND METHODS: Between January 1990 and May 1992, 47 eligible patients
      with multiple myeloma who had failed one prior chemotherapeutic regimen were
      accrued to a multiinstitutional prospective randomized clinical trial. The trial
      was halted early because of poor accrual. RESULTS: After a minimum follow-up of
      13 months, the objective overall response rate was 28% (25% in the VAD group, 30%
      in the VAD plus interferon group). The response duration and overall survival
      were similar for the two treatment groups, with medians of 3.6 and 8.3 months,
      respectively. Life-threatening or lethal nonhematologic toxicity was seen in 27%.
      Interferon did not appear to increase the frequency of toxic responses.
      CONCLUSION: This study shows no advantage to the use of interferon combined with
      VAD in refractory or relapsing myeloma. However, the small sample size decreased
      the statistical power to recognize small differences if present. Moreover, the
      survival data do not suggest a clear advantage to the administration of
      vincristine or doxorubicin as a 96-hour infusion compared with results of studies
      using bolus administration combined with high-dose corticosteroids.

PMID- 8526188
TI  - Prostate bed massage as a means to determine the source of a rising prostate
      specific antigen after radical prostatectomy.
AB  - PURPOSE: To determine the value of prostate bed massage as a means to determine
      whether a rising prostate specific antigen (PSA) after radical prostatectomy is
      due to local recurrence or distant metastases. METHODS AND MATERIALS: Eighteen
      patients referred for pelvic radiotherapy because of a rising PSA after radical
      prostatectomy had PSA levels measured immediately before and 5 minutes after a
      vigorous 30-second massage of the prostate bed. RESULTS: Only one of the 18 (5%)
      patients experienced a rise in their PSA following vigorous prostate bed massage.
      Fifteen of the 18 (83%) patients' PSA levels declined after radiotherapy,
      suggesting that recurrent prostate cancer had been present in the prostate bed at
      the time of prostate massage in these patients. Only 1 of these 15 patients (7%)
      had a rise in their PSA after massage. CONCLUSION: Prostate bed massage, as
      performed in this study, was not helpful to determine whether a rise in PSA after
      radical prostatectomy was due to local or distant recurrence.

PMID- 8526189
TI  - Phase II evaluation of low-dose continuous 5-fluorouracil and weekly cisplatin in
      advanced adenocarcinoma of the stomach. A Southwest Oncology Group study.
AB  - We have conducted a Phase II trial in patients with metastatic gastric cancer
      utilizing low-dose continuous infusion 5-fluorouracil (5FU) and weekly cisplatin
      (CDDP). The 5FU was administered at a dose of 200 mg/m2 per day by 24-hour
      continuous infusion via a permanent central venous catheter. The CDDP was
      administered at a dose of 20 mg/m2/week for the first 8 weeks, then every other
      week thereafter. Patients were evaluated for response every 8 weeks. There were 2
      complete and 2 partial responses out of 39 eligible and evaluable patients for an
      overall response rate of 10% (95% CI = 3-24%). The primary toxicities were
      nausea, hyponatremia, and anemia. Overall, treatment was well tolerated. We
      conclude that, although the treatment is relatively well tolerated, the regimen
      has minimal activity in this disease and does not deserve further study.

PMID- 8526190
TI  - Phase II trial of piritrexim and DTIC using an alternating dose schedule in
      metastatic melanoma.
AB  - A Phase II trial was conducted in patients with metastatic malignant melanoma
      with DTIC 250 mg/m2 intravenously for 5 days alternating monthly with Piritrexim
      (PTX) using an intermittent, low-dose oral administration schedule. PTX was
      administered at a starting dose of 25 mg orally three times per day for 5 days
      weekly for 3 weeks followed by 1 week of rest. Twenty-one patients were entered
      into the study. Among the 17 patients assessable for response, 1 patient had a
      minor response, and 3 patients had stable disease. No partial or complete
      response were observed. Toxicity was tolerable and consistent mainly of
      myelosuppression. Using this alternating dose schedule, PTX and DTIC produced
      little response in metastatic melanoma.

PMID- 8526191
TI  - High-dose busulfan and cyclophosphamide followed by autologous bone marrow
      transplantation and/or peripheral blood progenitor cell rescue for metastatic
      breast cancer.
AB  - High doses of combination alkylating agents have shown promise in the treatment
      of breast cancer but are complicated by significant toxicity. Busulfan and
      cyclophosphamide (BuCy) is a high-dose combination alkylating agent regimen that
      is well-tolerated when given for hematologic malignancy. We prospectively studied
      the effects of BuCy followed by autologous bone marrow transplant (ABMT) or
      peripheral blood progenitor cell (PBPC) rescue in 21 patients with metastatic
      breast cancer who had responded to either standard chemotherapy or radiotherapy.
      The mean patient age was 44 years. Nine patients were either estrogen- or
      progesterone-receptor positive, ten were negative, and two were unknown. Fourteen
      patients had local recurrence, ten had bone metastases, six had visceral disease,
      and two had a nonlocal soft tissue recurrence. Busulfan 16 mg/kg and
      cyclophosphamide 120 mg/kg (BuCy2) was given and followed by either ABMT, PBPC
      rescue, or both. Grade III to IV extramyeloid toxicity occurred in 6 (29%)
      patients. One patient died of hepatic venoocclusive disease but there was no
      other treatment-related mortality. Pulmonary infiltrates with hypoxia of
      uncertain origin developed in 2 patients after discharge. Of the 10 patients with
      measurable disease, 4 had complete responses, and 3 had partial responses to high
      dose therapy for a total response rate of 70%. The estimated 2-year disease-free
      survival is 25% (95% CI = 6% to 44%). Our study found BuCy to be a well-tolerated
      preparative regimen for ABMT in the treatment of patients with metastatic breast
      cancer.

PMID- 8526192
TI  - A phase II trial of gallium nitrate (NSC #15200) in nonsquamous cell carcinoma of
      the cervix. A Gynecologic Oncology Group study.
AB  - A Phase II trial of gallium nitrate for patients with recurrent or metastatic
      nonsquamous cell carcinoma of the cervix was conducted by the Gynecologic
      Oncology Group (GOG) from March 1988 to January 1992. Twenty-six evaluable
      patients were treated with 750 mg/m2 of gallium nitrate every 3 weeks. Age range
      was 30-74 years with a median of 48 years. GOG performance status was 0-1 for all
      but four patients. Two patients had a complete response (7.7%), 1 patient had a
      partial response (3.8%), 13 patients had stable disease (50.0%), and 10 (38.5%)
      had increasing disease. The 95% confidence interval for response is 2.4-30.2%.
      The major toxicities were nausea, vomiting, and anemia. Gallium nitrate has
      modest activity in patients with nonsquamous cell carcinoma of the cervix.

PMID- 8526193
TI  - Evaluation of ifosfamide plus mesna as first-line chemotherapy in women with
      metastatic breast cancer.
AB  - Ifosfamide is an oxazaphosphorine analogue of cyclophosphamide with proven
      activity in breast cancer but substantial urotoxicity. The introduction of mesna
      as a uroprotective agent provided a stimulus for reexamination of ifosfamide for
      therapy of women with metastatic breast cancer. Twenty women with measurable (18
      patients) or evaluable (2 patients) disease were entered into a phase II clinical
      trial of ifosfamide plus mesna as first-line chemotherapy. Ifosfamide was
      administered i.v. at a dose of 1,800 mg/m2 in 1 L D5W over 2 h on five
      consecutive days. Mesna was administered i.v. at a dose of 400 mg/m2 over 15 min
      immediately before and 1 h after ifosfamide, and then every 4 h for three more
      doses. The last three doses could be given either i.v. or orally. The planned
      cycle length was 28 days. Three patients (15%), all with measurable disease,
      achieved a partial response (95% confidence interval: 3 to 38%). Median time to
      progression was 137 days and median survival was 407 days. Toxicities included
      cumulative myelosuppression and substantial nausea and emesis. Four patients were
      removed from treatment because of toxicity alone and a fifth refused further
      therapy. We conclude that ifosfamide, plus mesna, as given in this protocol has
      definite but limited antitumor activity and poor tolerability.

PMID- 8526194
TI  - Radiation therapy for cancer of the piriform sinus. A failure analysis.
AB  - This paper analyzes the results of 109 piriform sinus (PS) cancers treated
      between 1973 and 1984 by surgery and/or external beam radiation therapy (EBRT) in
      a large comprehensive cancer center, and in particular tries to redefine the role
      of EBRT in the management of these tumors. At the time the policy was to start
      with EBRT to a dose of 40 Gy. A good response to a first series was to be
      continued by EBRT (RT-1); in case of poor responding tumors, the primary and neck
      were to be operated upon (RT-S). Poor responders unfit for S or those refusing S
      were also carried to a full course of EBRT (RT-2). The RT-S, RT-1, and RT-2
      actuarial 5-year locoregional relapse-free survival (LR-RFS) and overall survival
      (OS) were 60%, 40%, and 20% and 40%, 30%, and 20%, respectively. In a
      multivariate Cox regression analysis the most important prognostic factor
      appeared to be N-stage, with hazard ratios of 1.16 (N1), 2.2 (N2), and 3.3 (N3).
      The RT-S treatment group fared best (hazard ratio 0.5). The risk of relapse for
      T3,4 was 1.3 times as high as opposed to T1,2. For stage I/II (19/21 treated by
      EBRT only), a LR-RFS and OS at 5 years of 60% and 40%, respectively, was
      observed. This analysis supports data for stage III/IV PS cancers to be treated
      by surgery combined with EBRT; in stage I/II there might be a role for EBRT
      alone. It is speculated that with further sophistication in RT-techniques, the
      locoregional control rates by EBRT alone could improve.

PMID- 8526195
TI  - Thermoradiotherapy for brain tumors. Three cases of recurrent malignant
      astrocytoma and review of clinical experience.
AB  - Three patients with symptomatic, recurrent supratentorial malignant astrocytoma
      were retreated with combined interstitial iridium-192 brachytherapy (RT) and
      hyperthermia (HT): 50 Gy at 50 cGy/h was delivered 10 mm outside the computed
      tomography (CT) enhancement border through stereotactically placed plastic tubes,
      and 915-MHz microwave antenna heating was done for 60 min within 30 min either
      before or after irradiation. Invasive thermometry data were obtained from the
      tumor and adjacent brain tissue. The patients tolerated the treatment well and
      two thirds improved. All patients developed cerebral edema, one also developed
      scalp infection, and another patient developed meningeal infection. Exceeding the
      expectancy without treatment, overall survival was 7, 12, and 15 months. On
      autopsy, two of the patients' brains revealed no active tumor in the treated
      regions, but one displayed tumor in untreated parts. The HT-RT treatment was very
      effective, but the original tumor extent was not apparent by the CT imaging
      technique. A postimplant resection approach may be advisable to minimize
      postimplant edema. Our data are in agreement with the available literature on
      more than 400 patients. However, our aim of extending survival decisively could
      not be realized.

PMID- 8526196
TI  - Efficacy of the association of folinic acid and 5-fluorouracil alone versus
      folinic acid and 5-fluorouracil plus 4-epidoxorubicin in the treatment of
      advanced gastric carcinoma.
AB  - A total of 71 patients with advanced gastric carcinoma were randomized to receive
      either folinic acid + fluorouracil (arm A) or the same combination with the
      addition of 4-epidoxorubicin (arm B). Of the 62 evaluable patients (31 in both
      arms), six patients achieved a CR (10%) and 16 a PR (25.5%) with an overall
      response rate of 35.5% (29% in arm A and 42% in arm B; p = .28). Median duration
      of response was 6 and 7 months for arm A and B, respectively (p = .6). Responder
      patients showed a significantly better median survival duration than
      nonresponders (p = .01); in arm B the median survival duration was 16 months for
      responder patients in contrast to 7 months for nonresponders (p = .004). Toxicity
      was mild without significant differences between the two groups. There was one
      death due to hematological toxicity (arm A). The EPI-FA-FU combination appears
      effective and well tolerated with the additional advantage of being able to be
      administered in the outpatient clinic.

PMID- 8526197
TI  - Pilot phase II trial of 13-cis-retinoic acid and interferon-alpha combination
      therapy for advanced pancreatic adenocarcinoma.
AB  - The combination of interferons (IFNs) and retinoids in antineoplastic therapy is
      based upon preclinical, in vitro, and in vivo observations. Retinoid-IFN
      combinations have shown significant antitumor activity against advanced cutaneous
      and cervical squamous cell carcinoma (SCC), and the toxic effects do not appear
      to overlap. Based on in vitro evidence of synergy and observed clinical activity,
      we conducted a pilot phase II trial of 13-cis-retinoic acid (1 mg/kg/day) and IFN
      alpha (6 million units/day) in patients with advanced pancreatic adenocarcinoma.
      No objective responses occurred among six evaluable patients. The toxicities were
      mild and reversible, and grade 3 fatigue occurred in only one patient. No
      objective antitumor activity was noted against pancreatic adenocarcinomas at the
      dose and schedule utilized. Further exploration of this this purely biological
      approach is not warranted for pancreatic adenocarcinomas.

PMID- 8526198
TI  - Myxoid malignant fibrous histiocytoma: experience with chemotherapy.
AB  - Myxoid malignant fibrous histiocytoma (MFH) is an intermediate grade tumor with a
      definite metastatic potential but a relatively indolent natural history compared
      to the pleiomorphic variant of MFH. Little is known about its sensitivity to
      chemotherapy. We reviewed our experience with chemotherapy in myxoid MFH between
      1986 and 1992. The patient population was identified through a search of the
      database maintained by the Departments of Melanoma-Sarcoma Medical Oncology and
      Pathology: 55 patients with histologically confirmed diagnosis of myxoid MFH were
      identified. Chemotherapy was administered to 18 of these patients (10 females, 8
      males). The median age was 65 (range: 30-76). Ten patients had an extremity
      primary, seven had a trunk or retroperitoneal primary, and one patient had head
      and neck as the site of primary tumor. The median size of the primary tumor was
      11 cm (range: 5-23 cm) in maximum dimension. Seven patients received chemotherapy
      in the neoadjuvant setting, eight received it for recurrent or metastatic
      disease, and three received it postoperatively after complete resection of the
      tumor. All patients received doxorubicin and dacarbazine with or without
      cyclophosphamide. Of the 15 patients evaluable for response, 4 achieved an
      objective response (one CR, 3 PRs, RR = 27%) to a median of 3 cycles (range: 1-7
      cycles). At the time of last follow-up, eight patients are alive with no evidence
      of disease, two patients are alive with disease, and eight patients have expired.
      The median follow-up is 51 months (range: 26-216 months) from diagnosis. The
      relatively small sample precludes any definitive conclusions; however, it seems
      that doxorubicin- and dacarbazine-based chemotherapy has modest activity in
      myxoid MFH.

PMID- 8526199
TI  - Patient counseling regarding treatment of T1/2 (A/B) prostate cancer. A personal
      view.
AB  - Mr. Smith, a healthy 67-year-old man, has a "routine" prostate-specific antigen
      (PSA) of 7 ng/ml by Hybritech assay. No prostate abnormality was appreciated by
      digital rectal exam. Sextant biopsy revealed three cores positive for 3 + 3
      Gleason sum with an area of pattern 4. A bone scan was normal. The patient has no
      prior history of genitourinary disease, is continent, and is potent. I will
      review necessary background information concerning the therapy available for
      localized prostate cancer with Mr. Smith so that together we can identify the
      option most suited to the stage and grade of his disease, his general health, and
      his attitude or disposition to therapeutic interventions.

PMID- 8526200
TI  - Tumor-like lesions of the prostate gland.

PMID- 8526201
TI  - Diagnosis of heparin-induced thrombocytopenia. Still a journey, not yet a
      destination.

PMID- 8526202
TI  - Recommendations for the reporting of breast carcinoma. Association of Directors
      of Anatomic and Surgical Pathology.
AB  - The Association of Directors of Anatomic and Surgical Pathology (ADASP) has named
      several committees to develop recommendations regarding the content of the
      surgical pathology report for common malignant tumors. A committee of individuals
      with special interest and expertise write the recommendations, and they are
      reviewed and approved by the council of ADASP and subsequently by the entire
      membership. The recommendations have been divided into four major areas: (1)
      items that provide an informative gross description; (2) additional diagnostic
      features that are recommended to be included in every report if possible; (3)
      optional features that may be included in the final report; (4) A checklist (see
      Appendix). The purpose of these recommendations is to provide an informative
      report for the clinician. The recommendations are intended as suggestions and
      adherence to them is completely voluntary. In special clinical circumstances, the
      recommendations may not be applicable. The recommendations are intended as an
      educational resource rather than a mandate.

PMID- 8526203
TI  - Verumontanum mucosal gland hyperplasia in prostatic needle biopsy specimens. A
      mimic of low grade prostatic adenocarcinoma.
AB  - The histologic features of five cases of verumontanum mucosal gland hyperplasia
      (VMGH) in prostatic needle biopsy specimens are reported. All cases were
      initially reviewed in consultation by one of two of the authors (JIE or TMW) and
      in all cases, the submitted differential diagnosis included low grade
      adenocarcinoma. In all cases, VMGH was characterized by a relatively well
      circumscribed collection of closely packed glands, and was typically observed
      immediately subjacent to urothelium. A basal cell layer was readily identifiable
      in routine hematoxylin-and-eosin-stained sections. The luminal contents of the
      verumontanum mucosal glands were distinctive and consisted of lamellated
      eosinophilic concretions typical of corpora amylacea, as well as unique orange
      red concretions that were commonly fragmented. The histologic features of VMGH
      are characteristic and allow distinction from other small glandular
      proliferations of the prostate including nephrogenic adenoma, adenosis (atypical
      adenomatous hyperplasia), and low grade adenocarcinoma.

PMID- 8526204
TI  - A consensus polymerase chain reaction-oligonucleotide hybridization approach for
      the detection of chromosomal translocations in pediatric bone and soft tissue
      sarcomas.
AB  - Chromosomal translocations have been identified that are consistently associated
      with alveolar rhabdomyosarcoma and Ewing's sarcoma. Molecular diagnostic assays
      for these chromosomal translocations are important tools for the differential
      diagnosis of pediatric small round cell tumors presenting in the bones or soft
      tissues. However, the occurrence of variant chromosomal translocations in these
      cancers has complicated these molecular diagnostic approaches. To simplify the
      molecular detection of typical and variant translocations, the authors have
      developed an approach consisting of consensus reverse transcriptase-polymerase
      chain reaction and oligonucleotide hybridization steps. In the first step,
      consensus primers for each tumor type permit amplification of the chimeric
      transcripts resulting from both the common and variant translocations. In the
      second step, the common and variant translocations are distinguished by
      hybridization with gene-specific oligonucleotide probes. This approach provides a
      sensitive, specific, and efficient strategy for the detection of these
      chromosomal translocations.

PMID- 8526205
TI  - c-erbB-2 oncoprotein overexpression in uterine cervix carcinoma with glandular
      differentiation. A frequent event but not an independent prognostic marker
      because it occurs late in the disease.
AB  - The c-erbB-2 proto-oncogene (HER-2/neu) codes for a transmembrane, tyrosine
      kinase, 185 kD oncoprotein (p185erbB2), which is related to the epidermal growth
      factor receptor. p185erbB2 overexpression occurs in carcinomas at many sites,
      including the uterine cervix, and predicts poor clinical outcome. The authors
      hypothesize that p185erbB2 immunohistochemistry will provide additional
      information in the evaluation of uterine cervix carcinomas with glandular
      differentiation (CCGD), a difficult and more frequent clinical problem. Paraffin
      sections from 82 CCGDs including 41 pure adenocarcinomas and 41 adenosquamous
      carcinomas (7 glassy cell predominant and 34 exhibiting a gland forming
      component) are immunostained with anti-p185erbB2 (CB11 monoclonal, Novacastra
      Laboratories, Newcastle upon Tyne, UK). Seventy-seven percent of CCGDs exhibit
      p185erbB2 immunoreactivity with distinct plasma membrane localization (M) in 50%,
      the remaining 27% show cytoplasmic staining only. Adjacent benign tissue is
      negative. The p185erbB2 staining intensity and distribution is as follows: 54.9%
      strong diffuse (SD, > or = 50% cells positive) with 40.2% M, 17.1% strong focal
      (SF, < 50% cells positive) with 9.8% M, and 4.9% weak with no M. Immunoreactivity
      occurs in both squamous and glandular areas of adenosquamous carcinomas.
      Endometrioid histology is associated with absence of p185erbB2 (P < .01); all
      other histopathologic features show no association. Follow-up information is
      available in 77 patients: 37 exhibit recurrent disease (8 pelvic, 15 distant and
      14 both) at 1 to 144 months (mean 34, median 16) and 40 were disease free at 12
      to 216 months (mean 75, median 64). Strong p185erbB2 immunoreactivity predicts
      recurrence at 24 months (P < .05) but not overall recurrence at longer follow-up
      periods. Recurrent disease is associated with nuclear grade (P < .00001); high
      clinical stage (P < .001); vascular space invasion (P < .001); large size on
      clinical exam or pathologic evaluation (P < .005); and pelvic lymph node
      involvement (P < .05). Considering only patients in good prognosis groups,
      p185erbB2 immunoreactivity does not predict recurrence. Strong p185erbB2
      immunoreactivity is associated with stage 3,4 disease (P < .01). p185erbB2
      expression is associated with CCGD carcinogenesis but occurs late in the disease,
      in patients who present at late stage, hindering its prognostic predictive value.
      p185erbB2 immunolocalization may have a diagnostic role in confirming CCGD in
      histologically challenging cases, predicting high stage at initial biopsy, and
      defining therapeutic strategies.

PMID- 8526206
TI  - Syphilitic cervicitis simulating stage II cervical cancer. Report of two cases
      with cytologic findings.
AB  - Two women, ages 42 and 46, each had a cervical mass that clinically was grossly
      compatible with invasive carcinoma. Colposcopy supported the clinical impression.
      Weeks after the women were examined, it was determined that the masses
      represented syphilitic cervicitis. This entity has received almost no attention
      in the cytology literature, and is not discussed in major cytopathology texts.
      Accordingly, the cervicovaginal smears that were obtained in these cases are of
      interest. The smear pattern, which included lymphocytes, plasma cells,
      histiocytes, and debris, is described. Although in contrast, the histopathology
      of syphilitic cervicitis is well-characterized, diagnostic evidence of syphilis
      was missed in the initial interpretation of several of the biopsies. Syphilis
      recently has reemerged as a public health problem. Although the cases reported
      here represent rare events, pathologists should be aware that syphilitic
      cervicitis may clinically and colposcopically simulate a primary advanced
      cervical cancer. When interpreting cervical biopsies and cervicovaginal smears,
      they should be alert to patterns that suggest that syphilis is present.

PMID- 8526207
TI  - Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the
      diagnosis of heparin-induced thrombocytopenia.
AB  - The diagnosis of heparin-induced thrombocytopenia (HIT) may be affirmed by
      demonstrating heparin-dependent anti-platelet antibodies using the 14C-serotonin
      release assay (SRA). In this study, results of the SRA was compared with the
      recently described platelet factor 4 (PF4)/heparin enzyme-linked immunosorbent
      assay (ELISA). Compared with the SRA, the sensitivity and specificity of a
      PF4/heparin ELISA was 87% and 92%, respectively, using an assay developed in our
      laboratory; and 90% and 98%, respectively, using a commercially developed kit
      (Diagnostica Stago, Asnieres, France). However, antibodies to PF4/heparin were
      also detected in up to 8% of patients whose plasma was negative by SRA, and 23%
      of patients receiving heparin who were not thrombocytopenic. These data indicate
      that results obtained with the PF4/heparin ELISA and the SRA are generally in
      accord in patients with a clinical diagnosis of HIT. However, discrepant results
      occur in approximately 20% of cases because of the greater sensitivity of ELISA
      and the possible involvement of other heparin-binding proteins. The fact that
      each assay contributes independent information in some cases must be considered
      in the sequence of test performance and in providing consultation to the
      practicing hematologist.

PMID- 8526208
TI  - Adaptation of a functional assay for protein S to a Cobas Fara II centrifugal
      analyzer.
AB  - An adaptation of the manual Staclot protein S functional assay (American
      Bioproducts, Parsippany, NJ) for the Cobas FARA II centrifugal analyzer is
      described. This automated method is based on determining the clotting time by
      measuring the change in turbidity of the specimen as clotting progresses. The
      accurate and precise pipetting of the analyzer combined with its enhanced data
      acquisition and rapid parallel processing features result in a markedly improved
      procedure compared to the less accurate and reproducible manual method. The assay
      is linear over the range of protein S concentrations encountered clinically (0%
      to 150%); has a limit of detection of 3% protein S; within and between day
      precision (CV) at a level of 50% protein S is 4.7 and 12.6%, respectively; and
      results agree closely with those obtained on the STA automated hemostasis
      analyzer (slope = 0.98, intercept 3.92, and r = 0.98). Protein S values obtained
      with this assay for specimens from 20 normal males and 20 normal females were
      115% +/- 22.31% (mean +/- standard deviation [SD]) and 98% +/- 18.2%,
      respectively. In 14 patients on chronic stable treatment with Coumadin (DuPont
      Pharmaceuticals, Wilmington, DE) the mean functional protein S activity was 16.2%
      and the SD 11.7%. The method for determination of protein S activity on the
      centrifugal analyzer yields results comparable to data reported with a variety of
      other techniques.

PMID- 8526209
TI  - Hemolytic transfusion reaction due to Rh antibodies detectable only by manual
      polybrene and polyethylene glycol technique.
AB  - The authors report two cases of severe hemolytic transfusion reaction (HTR)
      attributable to Rh antibodies, which were not detectable by the saline indirect
      antiglobulin test (SIAT), low ionic strength saline solution technique (LISS), or
      two-stage enzyme (Enz) indirect antiglobulin test (IAT), but were readily
      detectable by the manual polybrene technique (MPT), MPT-IAT, and polyethylene
      glycol (PEG) IAT. With rare exceptions, Rh antibodies can usually be easily
      detected by the SIAT or Enz-IAT, and seldom cause intravascular HTR. The two
      cases in this report illustrate the value of the MPT and PEG-IAT in the detection
      of clinically significant Rh antibodies that would not otherwise be detectable by
      conventional methods.

PMID- 8526210
TI  - Combined superwarfarin and ethylene glycol ingestion. A unique case report with
      misleading clinical history.
AB  - A markedly elevated prothrombin time (PT) and activated partial thromboplastin
      time (APTT) were observed in a 24-year-old man who was admitted with a history of
      ethylene glycol ingestion. Further laboratory evaluation suggested that the
      coagulopathy was related to acquired factor deficiencies. The PT and APTT
      improved transiently on usual doses of vitamin K, but rapidly became abnormal
      again. The coagulopathy was controlled only after large doses of vitamin K for at
      least 37 days. On further questioning, the patient admitted to consuming a large
      quantity of a rodenticide. The second generation anticoagulant rodenticides
      (superwarfarins) result in a potent and prolonged anticoagulant effect by
      reducing the activity of the vitamin K dependent factors (II, XII, IX, and X). To
      our knowledge, this is the first reported concomitant ingestion of both ethylene
      glycol and a superwarfarin compound. This case serves to illustrate how a logical
      laboratory evaluation can lead to the proper diagnosis, despite a misleading
      clinical history.

PMID- 8526211
TI  - Comparative study of ELISA and indirect immunofluorescence for the detection of
      anti-neutrophil cytoplasmic antibodies. Evaluation of the SCIMEDX/EURO
      Diagnostica ELISA assay in a clinical setting.
AB  - This study evaluates the performance of a commercial ELISA assay for detection of
      anti-neutrophil cytoplasmic antibodies (ANCA). Anti-proteinase 3 (anti-PR3) and
      anti-myeloperoxidase (anti-MPO) ELISA by (SCIMEDX/EURO Diagnostica, Denville, NJ)
      were compared with the indirect immunofluorescence (IIF) method using ethanol
      fixed neutrophils. Three hundred sixty serum samples were examined. There was
      complete correlation of results in 357 (99.2%) cases between cANCA pattern and
      anti-PR3 results, and in 356 (98.9%) cases between pANCA pattern and anti-MPO
      ELISA results. The specificity of ELISA for detection of vasculitis was 95.7% and
      sensitivity was 60%, whereas for IIF, they were 95.7% and 65%, respectively. The
      ELISA showed good reproducibility with interassay variation (CV), ranging from
      7.1% to 13.2%. Our results show that SCIMEDX/EURO Diagnostica ELISA for ANCA is a
      reliable and reproducible method that is as good as IIF for detection of ANCA.

PMID- 8526212
TI  - Detection of hepatitis C after liver transplantation. Four serologic tests
      compared.
AB  - To determine the best method for detecting HCV infection in immunosuppressed
      patients, stored frozen serum from 101 liver transplant recipients was tested for
      hepatitis C virus. Each sample was tested by four assays. HCV RNA was detected by
      both polymerase chain reaction (PCR) and branched DNA signal amplification.
      Antibody to HCV was determined using second-generation enzyme-linked immunoassay
      (EIA) and recombinant immunoblot assay. Forty one transplant recipients met the
      working definition for true positives of HCV infection. Of these "true
      positives," 98% were positive by HCV RNA PCR assay, 88% by b-DNA signal
      amplification assay, 88% by anti-HCV EIA, and 63% demonstrated two or more
      reactive bands on recombinant immunoblot. Five of 57 (9%) HCV-antibody negative
      recipients had HCV RNA detected by both methods. Of 44 HCV enzyme-linked
      immunoassay (EIA) repeatedly reactive samples, the recombinant immunoblot was
      negative in 2 and indeterminate in 13. HCV RNA was present in 9 of 13 recombinant
      immunoblot indeterminate sera. Nine EIA repeatedly reactive sera were negative by
      both tests for HCV RNA. In liver transplant recipients, HCV infection is best
      determined by measurement of HCV RNA. Antibody formation may be delayed or
      suppressed in a minority of patients despite > 10(9) equivalents/L (> 10(6)/mL)
      of HCV RNA in serum. Recombinant immunoblots with a single reactive band pattern
      often indicate HCV infection in immunosuppressed patients.

PMID- 8526213
TI  - High frequency of CD45RO expression in AIDS-related B-cell non-Hodgkin's
      lymphomas.
AB  - Although immunophenotypic abnormalities have been reported in B-cell non
      Hodgkin's lymphomas (NHLs) occurring in the general population, there are no
      extensive studies on such abnormalities in AIDS-related B-cell NHLs. Reactivity
      of CD45RO/UCHL1 and expression of other T-cell associated antigens (CD43, OPD4,
      CD3, CD5, EMA) were examined by immunohistochemistry in 66 diffuse aggressive
      AIDS-related B-cell NHLs and in 296 AIDS-unrelated B-cell NHLs of similar
      morphology analyzed in the same institution. EBER in situ hybridization studies
      were also carried out in 57 of the 66 AIDS-related B-cell NHLs investigated.
      CD45RO/UCHL1 was expressed in 27% of AIDS-related B-cell NHLs, but only in 8% of
      diffuse aggressive AIDS-unrelated B-cell NHLs. The difference was highly
      significant (P < .001) overall and, within the Working Formulation subtypes,
      especially marked among small noncleaved cell (SNCC) lymphomas. Conversely, the
      reactivity of other T-cell associated antigens seemed to be very similar in AIDS
      related and AIDS-unrelated NHLs. However, for CD43, a significantly lower number
      of positive cases was found in AIDS-related NHLs among SNCC lymphomas. Among AIDS
      related B-cell NHLs, the highest frequency of CD45RO/UCHL1 expression was found
      in the immunoblastic subset with plasmacytoid differentiation. In the latter
      CD45RO/UCHL1 preferentially associated with EMA expression and EBV infection of
      the tumor clone, but not with CD45RA. The present finding of an excess of
      CD45RO/UCHL1 expression in AIDS-related B-cell lymphomas may reflect the
      preferential expansion of CD45RO expressing B-cell clones with putative
      autoreactive potential, as suggested by the expansion of CD45RO expressing B
      cells in autoimmune disorders.

PMID- 8526214
TI  - Detection of bcl-1 gene rearrangement and B-cell clonality in mantle cell
      lymphoma using formalin-fixed, paraffin-embedded tissues.
AB  - Mantle cell lymphoma (MCL) has recently emerged as a distinct clinicopathologic
      entity with characteristic molecular genetic features. Specifically, MCL are
      clonal B-cell neoplasms and often harbor bcl-1 gene rearrangements. Although this
      genetic profile is well documented, scant or no data are available on the
      molecular assessment of MCL using formalin-fixed, paraffin-embedded tissue as a
      sample source. The polymerase chain reaction (PCR) was employed to study bcl-1
      and immunoglobulin heavy chain (IgH) gene rearrangements (B-cell clonality) using
      formalin-fixed tissue from 12 cases of MCL. In addition, 12 cases of low grade B
      cell lymphoma and 5 cases of reactive lymphocytic hyperplasia were studied as
      comparison controls. A hemi-nested PCR assay was developed to identify major
      translocation cluster (MTC) bcl-1 gene rearrangements, whereas IgH gene
      rearrangements were evaluated by both a single-step and hemi-nested approach. Bcl
      1 gene rearrangements were amplified in 4 of 12 (33%) MCL, but in none of the
      controls. With the hemi-nested approach, B-cell monoclonality was demonstrated in
      11 of 12 (92%) MCL; 6 of 6 (100%) small lymphocytic lymphomas; 1 of 2 marginal
      zone lymphomas; 1 of 4 follicular lymphomas; and 0 of 5 reactive lymphocytic
      hyperplasias. When one-step PCR was used for B-cell clonality assessment, the
      overall detection rate was lower, specifically: 8 of 12 (67%) MCL; 4 of 6 (67%)
      small lymphocytic lymphomas; 1 of 2 marginal zone lymphomas; 0 of 4 follicular
      lymphomas; and 0 of 5 reactive lymphocytic hyperplasias were identified as
      monoclonal. We have demonstrated that MTC bcl-1 gene rearrangements can be
      amplified from formalin-fixed tissue. In addition, monoclonal B-cell populations
      from MCL are better amplified with a hemi-nested approach rather than a single
      step PCR assay. With specialized nucleic acid isolation techniques and
      appropriate PCR protocol design, formalin-fixed, paraffin-embedded tissue is an
      adequate source of DNA for assessing MTC bcl-1 and IgH gene rearrangements.

PMID- 8526215
TI  - Dendritic cell tumors associated with low-grade B-cell malignancies. Report of
      three cases.
AB  - Indeterminate and interdigitating cell tumors are rare proliferations of
      immunoregulatory cells that demonstrate morphologic, immunologic, and
      ultrastructural features similar to their cells of origin. Although an
      association of lymphoproliferative disease with Langerhans' cell histiocytosis is
      well described, only sporadic cases of non-Langerhans' dendritic cell
      proliferations have been published. The authors describe three patients with low
      grade B-cell lymphoproliferative disease who developed subsequent indeterminate
      cell or interdigitating cell tumors. When the two cases of indeterminate cell
      tumor are added to those previously described in the literature, it appears that
      4 of 13 cases (31%) are associated with a history of low grade B-cell malignancy.
      Possible explanations for the relationship between these two disorders are
      discussed.

PMID- 8526216
TI  - gamma/delta T cells in HIV seropositive and seronegative individuals.

PMID- 8526217
TI  - Perforin in GVHD.

PMID- 8526218
TI  - Gastric carcinoma with osteoclast-like giant cells.

PMID- 8526219
TI  - American Occupational Therapy Association and American Occupational Therapy
      Foundation outcomes-related activities.

PMID- 8526220
TI  - Development of in-hand manipulation and relationship with activities.
AB  - OBJECTIVES: This study examines the age-related increase of in-hand manipulation,
      the consistency of using a manipulation strategy, and the relationship between
      the frequency of in-hand manipulation and activities that typically require use
      of intrinsic hand control. METHOD: Children (N = 184) between 2 years and 7 years
      of age were observed during selected activities that could elicit three forms of
      in-hand manipulation: rotation, finger-to-palm translation, and palm-to-finger
      translation. The child's use of a manipulation strategy was recorded. Activities
      that required manipulation of objects including a spoon, buttons, and crayons
      were also observed. RESULTS: The study demonstrated that the frequency of two
      types of in-hand manipulation increases with age and illustrated the uneven
      nature of development of different types of in-hand manipulation. Even when the
      child had the ability, use of in-hand manipulation as a movement strategy was
      inconsistent. Small but significant relationships between in-hand manipulation
      skill and performance in selected activities were found when the effects of age
      were controlled. CONCLUSION: On a practical level, the findings raise questions
      as to whether maturity of in-hand manipulation may be a factor limiting
      performance in the everyday activities of typically developing children.

PMID- 8526221
TI  - Clinical interpretation of "development of in-hand manipulation and relationship
      with activities".

PMID- 8526222
TI  - Effects of afternoon rest on the performance of geriatric patients in a
      rehabilitation hospital;: a pilot study.
AB  - OBJECTIVE: When a person is hospitalized, he or she enters an environment in
      which time is structured very differently than it is in everyday life. Research
      with healthy young subjects in sleep laboratories has indicated that disruption
      in activity-rest cycles significantly affects mood, physical skills, and
      cognitive performance. Older persons whose daily routines are upset when they
      become patients in a hospital may be even more vulnerable to performance
      deficits. This pilot study was implemented in a regional rehabilitation center as
      an initial step in exploring the relationships between variations in schedule and
      geriatric patients' functioning while hospitalized. METHOD: Single-subject
      methodology was used to study six elderly fracture patients' responses to the
      addition of an afternoon nap to their daily routine. Data were collected each
      morning and afternoon, during "nap" and "no nap" weeks, with simple measures of
      alertness, concentration, strength, coordination, and reaction time. RESULTS:
      Tendencies toward late afternoon drowsiness and, in some cases, improved
      cognitive performance, were observed when naps were provided. CONCLUSION: Data
      about the ways in which hospital routine affects performance can guide
      occupational therapists in advocating for balanced programs of activity and rest
      for older rehabilitation patients.

PMID- 8526223
TI  - Impact of spinal cord injury on the life roles of women.
AB  - This qualitative study was conducted to explore and describe the role experience
      of five women whose lives were disrupted by a traumatic spinal cord injury and
      who later returned to their communities after completing intensive rehabilitation
      programs. In-depth interviews and participant observations were used to examine
      the experiences of these women. The findings exemplify how the women's use of
      adaptation and negotiation and the development of a new role as self-advocate
      facilitated the reestablishment of their life roles. As the women's occupational
      roles were redefined, the processes of adaptation and negotiation were evident in
      three aspects of their lives: daily routines, relationships, and environment.
      Through their new role of self-advocate, architectural and attitudinal barriers
      were negotiated and adapted so that roles could be explored. These findings
      indicate that community reentry involves the ongoing process of negotiation and
      adaptation of life roles. The use of life histories during the rehabilitation
      phase is suggested as a way for therapists to develop meaningful treatment plans
      that stimulate patients' adaptation process and ultimately enhance community
      reentry.

PMID- 8526224
TI  - Motor problems in children with developmental coordination disorder: review of
      the literature.
AB  - Occupational therapists frequently work with children with developmental
      coordination disorder (DCD) in hopes of enhancing their occupational performance.
      There is debate among researchers and health care professionals about whether the
      motor coordination problems experienced by children with DCD have a physiological
      basis or whether they are the result of a developmental delay. Even among
      researchers who agree that these difficulties are of physiological origin, there
      is a lack of consensus as to whether these motor problems are multisensory or
      unisensory. This article focuses on the physiological explanation, presents a
      review of the literature on the possible physiological origins of motor
      coordination problems in children with DCD, and shows that the current literature
      on the physiological basis of DCD requires more empirical evidence to
      substantiate either multisensory or unisensory theories of motor dysfunction in
      children with DCD. The debate over the nature of motor problems in children with
      DCD has two implications for occupational therapists: that there is no one way to
      treat these children and that the cause of the difficulty varies from child to
      child.

PMID- 8526225
TI  - The touch inventory for elementary-school-aged children: test-retest reliability
      and mother-child correlations.
AB  - OBJECTIVE: The Touch Inventory for Elementary-School-Aged Children (TIE) is a
      self-report screening assessment for tactile defensiveness. The purpose of this
      study was to examine test-retest reliability of the TIE and to evaluate agreement
      between children's TIE scores and scores that mothers gave their children on a
      modified version of the TIE. METHOD: Twenty-nine children, 6 to 12 years of age,
      were available for the test-retest portion of the study and were assessed with
      the TIE with a 1-week interval between sessions. Their mothers completed a
      modified version of the TIE. RESULTS: Results indicated significant test-retest
      reliability (r = .91, p < .001), although a more conservative Kappa indicated
      only moderate agreement. The correlation between mothers' ratings and children's
      ratings was less significant (r = .56, p = .001), and Kappas were slight or fair,
      indicating considerable disagreement between mothers and children. CONCLUSION:
      These results suggest that using information from both mothers and children might
      provide a more complete picture of tactile defensiveness, but further research is
      needed before using a mother's assessment when the TIE is implemented as a
      standard procedure.

PMID- 8526226
TI  - Understanding the family perspective: an ethnographic framework for providing
      occupational therapy in the home.
AB  - This article presents a framework for providing occupational therapy services to
      family members caring for elderly persons in the home that is based on four key
      principles derived from ethnographic methodology: identification of an informant,
      use of an emic (insider) approach, engagement in self-reflection, and
      interpretation of information. The underlying strategy is to use these principles
      to derive an understanding of the personal meaning of caregiving, the way in
      which care is provided, and the specific aspects of caregiving that are
      problematic from the perspective of the family member. Services are then
      developed that reflect individual need as expressed by the caregiver and that fit
      the fundamental values and belief system of the family unit. A case example is
      presented to illustrate the framework in action in a home situation with family
      members caring for an elderly person with dementia.

PMID- 8526227
TI  - Assistive devices used by home-based elderly persons with arthritis.
AB  - OBJECTIVE: This article examines assistive device use by home-based elderly
      persons with arthritis. METHOD: Sixty-six persons were interviewed for the State
      University of New York at Buffalo (University at Buffalo) Rehabilitation
      Engineering Research Center Consumer Assessment Study, which sought information
      on need for and current use of assistive devices. Subjects were assigned to a
      moderate or a severe arthritis group according to the impact of arthritis on
      their activities. RESULTS: Subjects in the severe arthritis group had more
      chronic diseases, a higher level of pain, and a lower level of independence in
      self-care activities than subjects in the moderate arthritis group. Similarities
      between the groups included relatively poor health, high rate of medication use,
      depression, use of a high number of assistive devices (about 10 per person), and
      an expressed need for additional devices, such as reachers, magnifiers, grab
      bars, jar openers, and hearing aids. Generally, there was a high rate of
      satisfaction with the assistive devices used. Most subjects missed being able to
      participate in at least one activity; most of these activities were active and
      many related to leisure time. CONCLUSION: Findings also revealed that subjects
      had inadequate information on assistive devices, which suggests the importance of
      more occupational therapy involvement with elderly persons in selecting devices.

PMID- 8526228
TI  - Computer-assisted instruction as a learning resource for applied anatomy and
      kinesiology in the occupational therapy curriculum.
AB  - OBJECTIVES: The purpose of these studies was to examine the learning outcomes of
      a computer-assisted instruction (CAI) tutorial in applied anatomy and kinesiology
      for occupational therapy students and to determine its applicability for use in
      two university settings. METHOD: Two separate pilot studies were conducted at two
      universities. In each study, the learning outcomes of an experimental group of
      occupational therapy students using a CAI program and a control group using books
      to study the same material were compared. Learning outcomes were assessed with
      post-test achievement test scores on an applied anatomy and kinesiology test and
      responses to an attitude questionnaire with Likert-scale items and open-ended
      questions. RESULTS: There was no significant difference in the means on
      achievement test scores for the experimental and control groups in the first
      pilot study. In the second study, the CAI group scored significantly higher on
      the achievement test than the control group. In both pilot studies, subjects
      displayed significantly more positive attitudes toward the CAI program as a
      learning tool than they did toward traditional self-study with books. CONCLUSION:
      A CAI program in applied anatomy and kinesiology can be an effective supplemental
      resource for occupational therapy students and can offer a learning experience
      that students value and perceive as helpful. Establishment of clear learning
      objectives, use of a theoretical base to design instruction, and development and
      testing in different educational settings can help improve the quality of CAI
      programs and ensure their relevance to other curricula.

PMID- 8526229
TI  - The profession's image, 1917-1925, Part II: Occupational therapy as represented
      by the profession.
AB  - This second part of a two-part article examines the representation of
      occupational therapy during its formative years, 1917-1925. It focuses on the
      image of the profession as it was described in the early professional journals
      and compares this image with that projected by the media (as described in Part
      I). Both the media and professional literature presented a similar image of
      occupational therapy: that of a profession that offered the promise of returning
      persons with disabilities to useful occupation within society. In today's health
      care system, where every profession espouses the goal of returning patients to
      full functioning, it is important to remember that in 1917 only one profession
      held that goal. The portrayal in the media and in the professional literature of
      occupational therapy at that time confirms this image.

PMID- 8526230
TI  - What is the role of the occupational therapist in managed care?

PMID- 8526231
TI  - Research grant policies and current research funding priorities of the American
      Occupational Therapy Foundation.

PMID- 8526232
TI  - More clues on "latent" schizophrenia point to developmental origins.

PMID- 8526233
TI  - Images in neuroscience. Neuroimaging, III. PET and the [15O]H2O Technique, Part
      1: Statistical Analysis of Images.

PMID- 8526234
TI  - Conflict between current knowledge about posttraumatic stress disorder and its
      original conceptual basis.
AB  - OBJECTIVE: The author's goal was to explore the historical, political, and social
      forces that have played a major role in the acceptance of the idea of trauma as a
      cause of the specific symptoms of posttraumatic stress disorder (PTSD) and to
      discuss the impact that current research findings have had on some of the initial
      conceptualizations of the disorder. METHOD: The conceptual origins of PTSD are
      described, and the literature on the prevalence, longitudinal course,
      phenomenology, and neurobiology of PTSD is reviewed. RESULTS: Paradoxically,
      there are a series of findings that support the idea that PTSD is a distinct
      diagnostic entity, but these are different from those originally developed from
      psychosocial theory and stress research. CONCLUSIONS: PTSD has been a
      controversial diagnosis and is again at a vulnerable point. It is imperative that
      the field address how current findings challenge the original conceptualizations
      of this disorder so that the next generation of conceptual issues can be
      formulated.

PMID- 8526235
TI  - Maternal influenza, obstetric complications, and schizophrenia.
AB  - OBJECTIVE: Epidemiologic studies have reported an association between prenatal
      exposure to influenza and adult schizophrenia. The authors studied this
      association in individual patients with schizophrenia and also investigated the
      relationship of obstetric complications, another postulated risk factor, to adult
      schizophrenia. METHOD: Using a structured interview instrument, the authors
      assessed infections during pregnancy, obstetric complications, gestational age,
      and birth weight by interviewing the mothers of 121 patients with DSM-III-R
      schizophrenia. RESULTS: Significantly more infections were reported in the second
      trimester of the patients' gestations than in the combined first and third
      trimesters. Influenza accounted for 70% of second-trimester infections. Patients
      with schizophrenia whose mothers reported having influenza during the second
      trimester were almost five times more likely to experience at least one definite
      obstetric complication than were patients who were not exposed to influenza
      during the second trimester; the exposed patients weighed a mean of 210 g less at
      birth than the unexposed patients. CONCLUSIONS: Maternal influenza during the
      second trimester may impair fetal growth and predispose to obstetric
      complications and lower birth weight in a proportion of individuals destined to
      develop schizophrenia.

PMID- 8526236
TI  - Brain morphology in first-episode schizophrenia.
AB  - OBJECTIVE: Neuroimaging studies have provided robust evidence that schizophrenia
      is associated with structural brain abnormalities. However, the underlying
      pathophysiology of these changes is still unknown. By evaluating brain morphology
      early in the course of illness, confounding effects of treatment and duration of
      illness are minimized. The goal of this study was to evaluate brain structure in
      patients early in the course of schizophrenia who had received no or minimal
      neuroleptics. METHOD: Magnetic resonance imaging was used to evaluate 12 male and
      12 female patients experiencing their first episode of schizophrenia (mean
      duration of psychotic episode = 14 weeks) and 12 male and 12 female normal
      volunteers equivalent in age, height, and parents' socioeconomic status. A
      totally automated method was used to analyze scans, yielding volumes of brain
      tissue and CSF, divided into lobes. RESULTS: The patient group had significantly
      more total CSF than the comparison subjects. This was accounted for by higher
      levels of intersulcal CSF as well as ventricular CSF. There were no differences
      in total volume of brain tissue between the two groups, but patients had a
      significant regionally specific decrement in frontal lobe tissue compared with
      the normal subjects. CONCLUSIONS: These findings indicate that structural brain
      abnormalities are present very early in schizophrenia and may not be due to
      factors such as treatment or chronicity of illness. Rather, since the
      abnormalities are present near the onset of the illness, a neurodevelopmental
      mechanism may be suggested.

PMID- 8526237
TI  - Prevalence and clinical correlates of extrapyramidal signs and spontaneous
      dyskinesia in never-medicated schizophrenic patients.
AB  - OBJECTIVE: This study assessed the prevalence of extrapyramidal signs and
      spontaneous dyskinesia in neuroleptic-naive, first-episode schizophrenic patients
      and examined the clinical correlates. METHOD: In a prospective study of the
      psychobiology of schizophrenia, the authors examined 89 neuroleptic-naive
      patients for the presence of extrapyramidal signs by using the Simpson-Angus
      Rating Scale and for dyskinesia by using the Tardive Dyskinesia Rating Scale.
      RESULTS: Fifteen patients (16.9%) had extrapyramidal signs, but only one had
      spontaneous dyskinesia at baseline. Presence of extrapyramidal signs was
      correlated with more negative symptoms and poorer treatment outcome that was
      reflected in a longer time to and lower level of remission. There was no
      correlation of spontaneous extrapyramidal signs with age of patient, age at onset
      of psychotic symptoms, or baseline psychopathology. There was no difference
      between patients with and without spontaneous extrapyramidal signs in terms of
      the subsequent development of persistent tardive dyskinesia, but the patients
      with spontaneous extrapyramidal signs were more likely to develop parkinsonian
      side effects after 8 weeks of antipsychotic treatment. CONCLUSIONS:
      Extrapyramidal signs are present in a proportion of neuroleptic-naive, first
      episode schizophrenic patients, which suggests an involvement of these signs in
      the schizophrenic process that probably reflects basal ganglia pathology. The
      presence of spontaneous extrapyramidal signs seems to have prognostic
      significance insofar as it is linked to a poorer outcome and longer time to
      remission. Spontaneous dyskinesia appears to be a relatively rare finding.

PMID- 8526238
TI  - Tardive dyskinesia and substrates of energy metabolism in CSF.
AB  - OBJECTIVE: This study was undertaken to assess the relationships among CSF
      concentrations of substrates of mitochondrial energy metabolism, neuroleptic
      medication, and neurological side effects. METHOD: CSF was obtained from 25
      patients with schizophrenia; seven were unmedicated and 11 had tardive
      dyskinesia. CSF concentrations of four substrates of mitochondrial energy
      metabolism (Krebs cycle)--alanine, aspartate, lactate, and pyruvate--were
      determined. Tardive dyskinesia was measured with the Abnormal Involuntary
      Movement Scale (AIMS), and parkinsonism was measured with the Simpson-Angus
      Rating Scale. RESULTS: CSF concentrations of alanine were significantly elevated
      in the medicated patients when tardive dyskinesia status was controlled for. CSF
      aspartate concentrations were significantly elevated in patients with tardive
      dyskinesia when medication status was controlled for and were significantly
      correlated with total scores on the AIMS. CONCLUSIONS: These results are
      consistent with a model linking neuroleptic-induced neurological side effects
      with impairment of mitochondrial energy metabolism, possibly mediated by
      inhibition of complex 1 of the electron transport chain.

PMID- 8526239
TI  - Impairment of recognition memory with, but not without, conscious recollection in
      schizophrenia.
AB  - OBJECTIVE: To test the hypothesis that there is a link between the memory deficit
      associated with schizophrenia and an impairment of consciousness, an experiential
      approach was used to assess recognition memory and awareness in schizophrenic
      patients and normal subjects. METHOD: On a recognition memory task with low- and
      high-frequency words, the schizophrenic (N = 30) and normal (N = 30) subjects
      gave "remember" responses to recognized items that were accompanied by conscious
      recollection and "know" responses to items that were recognized on the basis of
      familiarity without any recollective experience. RESULTS: Schizophrenia
      selectively impaired recognition based on recollective experience, as measured by
      "remember" responses, but had no effects on "know" responses. In the comparison
      group, low-frequency words, relative to high-frequency words, enhanced conscious
      recollection but not familiarity. The schizophrenic patients did not display the
      same word-frequency effect. CONCLUSIONS: These results indicate that
      schizophrenia affects differentially two means of access to the personal past: it
      impairs recognition memory with, but not without, conscious recollection. They
      suggest that the impairment of conscious recollection observed in schizophrenic
      patients could be due to a failure of elaborative processing of information.

PMID- 8526240
TI  - Epidemiology, diagnosis, and course of brief psychoses.
AB  - OBJECTIVE: This study investigated acute and nonacute brief psychoses. On the
      basis of previous work, the authors proposed that 1) acute brief psychoses occur
      predominantly in females, 2) they often do not conform to the diagnoses of DSM
      III-R, 3) they are temporally stable, and 4) nonacute brief psychoses do not
      share these distinctive features. METHOD: The data are from a follow-up study of
      221 first-admission patients with affective and nonaffective psychoses. Patients
      were given extensive assessments at initial evaluation, 6-month follow-up, and 24
      month follow-up. The research team made consensus ratings of the presence of
      psychosis, DSM-III-R diagnosis, mode of onset of disorder, and course of
      disorder. Brief psychoses were defined by a diagnosis of nonaffective psychosis
      at the initial evaluation and a rating of full remission at 6-month follow-up;
      acute brief psychoses met the additional criterion of acute onset as defined by
      ICD-10. RESULTS: Twenty (9%) of the 221 psychoses were brief psychoses. Only
      seven (3%) were acute brief psychoses, but among these, six occurred in women,
      five were undiagnosable, and none had evolved into an affective disorder or a
      chronic disorder by the time of the 24-month follow-up. The 13 nonacute brief
      psychoses did not exhibit distinctive features, and five of them later evolved
      into chronic disorders. CONCLUSIONS: Acute brief psychoses emerged as a highly
      distinctive and temporally stable form of psychosis that may merit a separate
      diagnostic classification. The more numerous nonacute brief psychoses may
      represent mild forms of nonaffective psychoses such as schizophrenia.

PMID- 8526241
TI  - Identifying modifiable risk factors for rehospitalization: a case-control study
      of seriously mentally ill persons in Mississippi.
AB  - OBJECTIVE: The authors sought to identify risk factors for rehospitalization in a
      seriously mentally ill population, focusing on factors that have the potential to
      be modified through community-based interventions. METHOD: A case-control design
      was used in which 101 "case" subjects (recently readmitted psychiatric patients)
      and a comparison group of 101 subjects living in the community who had been
      previously hospitalized at the same time as the case subjects, but who in
      contrast had not been readmitted, were matched on gender, ethnicity, and length
      of time at risk for rehospitalization. The setting was the Mississippi public
      mental health system during the first 3 months of 1988, including Mississippi
      State Hospital and the 10 community mental health regions in its catchment area.
      The subjects were between the ages of 18 and 55 years, had had at least one
      previous Mississippi State Hospital admission, and had a primary chart diagnosis
      of schizophrenia; 197 informants, mostly family members, were also included in
      the study. Data were collected from structured interviews of subjects and
      informants, direct observation ratings of subjects, Mississippi State Hospital
      administrative records, and community mental health center administrative
      records. RESULTS: Medication noncompliance, comorbid alcohol abuse, and a high
      level of criticism of subjects by informants were associated with greater risk of
      rehospitalization, while types and extent of outpatient service use, access to
      care, quality of life, and demographic variables (other than ethnicity and
      gender) were not. CONCLUSIONS: These findings imply that interventions aimed at
      improving medication compliance, reducing alcohol abuse, and helping families
      cope with their mentally ill relatives could reduce the risk of hospitalization
      in this population.

PMID- 8526242
TI  - Predictors of cognitive change in middle-aged and older adults with memory loss.
AB  - OBJECTIVE: Previous longitudinal studies of age-related memory loss have focused
      on objective neuropsychological measures that predict subsequent cognitive
      change, yet brain metabolic function, self-perception of memory loss, and other
      measures may also be sensitive indicators of cognitive change. To determine such
      baseline predictors of change, the authors made longitudinal assessments of
      middle-aged and older adults with memory loss. METHOD: Forty-two persons (mean
      age = 60 years, range = 43-81) with memory complaints received comprehensive
      baseline assessments, including subjective neuropsychological measures, objective
      measures of visual-spatial memory (the Benton Visual Retention Test) and verbal
      memory (the Buschke-Fuld Selective Reminding Test), and positron emission
      tomography scans to determine neocortical glucose metabolism. At an average
      follow-up of 3 years, the objective neuropsychological measures were again used
      to quantify the degree of cognitive change. RESULTS: Multiple regression analyses
      indicated that parietal asymmetry, sex of the subject, and baseline visual
      spatial memory score were significant predictors of change in visual-spatial
      memory; level of education and baseline verbal memory score predicted change in
      verbal memory. Other neocortical asymmetry scores, age, family history of
      Alzheimer's disease, cerebral atrophy, and self-ratings of use of mnemonics were
      not significant predictors of change. CONCLUSIONS: Measures of cerebral
      metabolism, objective memory performance, sex, and education may predict
      subsequent cognitive change in middle-aged and older persons with memory loss.
      Also, the parietal asymmetry found in persons with questionable dementia that
      progresses to probable Alzheimer's disease may be present very early in the
      course of age-related cognitive decline.

PMID- 8526243
TI  - Multicenter, placebo-controlled study of fluoxetine in seasonal affective
      disorder.
AB  - OBJECTIVE: The authors investigated the efficacy and safety of fluoxetine in the
      treatment of winter seasonal affective disorder. METHOD: Sixty-eight outpatients
      who met the DSM-III-R criteria for recurrent major depressive episodes, seasonal
      (winter) pattern, were randomly assigned to 5 weeks of treatment with fluoxetine,
      20 mg/day (N = 36), or placebo (N = 32). The outcome measures included the 29
      item modified Hamilton Depression Rating Scale, administered by experienced
      clinicians, and the self-rated Beck Depression Inventory; adverse events and
      safety data were also recorded. Clinical response was defined as a greater than
      50% reduction in depression score between baseline and study termination.
      RESULTS: Both groups showed significant improvement. The fluoxetine group had
      lower depression scores at termination than the placebo group, but these
      differences did not achieve statistical significance. However, the rate of
      clinical response in the fluoxetine group (59%) was superior to that in the
      placebo group (34%). Post hoc analyses showed that the greatest fluoxetine
      responses were in the most markedly depressed patients and that overall response
      was greater for patients studied later in the season. Fluoxetine was well
      tolerated, and few subjects dropped out because of adverse events. CONCLUSIONS:
      On the basis of clinical response rate, fluoxetine appears to be an effective,
      well-tolerated treatment for seasonal affective disorder. Because the differences
      between fluoxetine and placebo in the continuous outcome measures did not reach
      statistical significance, further studies with larger study groups and longer
      treatment periods are required to conclusively demonstrate efficacy of fluoxetine
      for seasonal affective disorder.

PMID- 8526244
TI  - Trial of d-alpha-tocopherol in Huntington's disease.
AB  - OBJECTIVE: Evidence suggests that the neuropathology of Huntington's disease, a
      neuropsychiatric disorder due to a mutation on chromosome 4, results from
      excessive activation of glutamate-gated ion channels, which kills neurons by
      oxidative stress. Therefore, the authors hypothesized that alpha-tocopherol,
      which reduces oxyradical damage to cell membranes, might slow the course of
      Huntington's disease. METHOD: A prospective, double-blind; placebo-controlled
      study of high-dose d-alpha-tocopherol treatment was carried out with a cohort of
      73 patients with Huntington's disease who were randomly assigned to either d
      alpha-tocopherol or placebo. Patients were monitored for changes in neurologic
      and neuropsychologic symptoms. RESULTS: Treatment with d-alpha-tocopherol had no
      effect on neurologic and neuropsychiatric symptoms in the treatment group
      overall. However, post hoc analysis revealed a significant selective therapeutic
      effect on neurologic symptoms for patients early in the course of the disorder.
      CONCLUSIONS: Antioxidant therapy may slow the rate of motor decline early in the
      course of Huntington's disease.

PMID- 8526245
TI  - Somatic symptoms and HIV infection: relationship to depressive symptoms and
      indicators of HIV disease.
AB  - OBJECTIVE: This study examined the relationship of the somatic symptoms fatigue
      and insomnia with indicators of both psychiatric disturbance and HIV disease
      severity. METHOD: Study participants were 98 asymptomatic HIV-infected and 71
      uninfected homosexual men; 82 HIV-infected and 64 uninfected men had 6-month
      follow-up examinations. Scales from the self-reported Profile of Mood States
      measured fatigue and dysphoric mood. Major depression diagnosis was determined by
      the Structured Clinical Interview for DSM-III-R. Selected items from the Hamilton
      depression and anxiety scales measured insomnia and other symptoms of depression.
      Performance on a battery of standardized tests determined neuropsychological
      function ratings. RESULTS: At study entry, complaints of fatigue and insomnia
      were associated with dysphoric mood, major depression, and other non-HIV-related
      symptoms of major depression but not with CD4 cell counts or neuropsychological
      functioning. Increases in levels of fatigue and insomnia over the 6-month follow
      up period were associated with increases in non-HIV-related symptoms of
      depression and in severity of dysphoric mood. Increases in fatigue were also
      associated with decrements in motor functioning. Otherwise, fatigue or insomnia
      were not associated with HIV disease progression. CONCLUSIONS: These findings
      suggest that complaints of fatigue and insomnia in otherwise asymptomatic HIV
      infected patients are likely to be related to psychological disturbances and
      possibly major depression, which can be treated. HIV-infected patients who
      complain of fatigue or insomnia should routinely be assessed for major
      depression.

PMID- 8526246
TI  - Cerebral glucose metabolism, CSF 5-HIAA levels, and aggressive behavior in rhesus
      monkeys.
AB  - OBJECTIVE: Considerable evidence suggests that low concentrations of 5
      hydroxyindoleacetic acid (5-HIAA) in CSF are associated with a history of
      aggressive behavior in both human and nonhuman primates. The purpose of this
      investigation was to examine the relationships among CSF 5-HIAA concentration,
      history of aggressive behavior, and cerebral glucose metabolism in a group of
      nonhuman primates whose CSF 5-HIAA had been sampled several times over the
      preceding 2 years and whose social behavior had been observed since birth.
      METHOD: The subjects were nine adult male rhesus monkeys studied under isoflurane
      anesthesia. Cerebral glucose utilization was measured by [18F]fluorodeoxyglucose
      positron emission tomography. Aggressiveness ratings were made by a primatologist
      who had had frequent contact with the animals over several years. RESULTS: There
      was a significant negative correlation between ratings of aggressive behavior and
      CSF 5-HIAA concentrations. There was also a negative correlation between the dose
      of pentobarbital required to induce anesthesia and level of CSF 5-HIAA. Moreover,
      there were significant negative correlations between CSF 5-HIAA levels and both
      whole brain glucose utilization and regional glucose utilization in the orbital
      frontal cortex. CONCLUSIONS: These results suggest that both increased
      aggressiveness and low concentrations of CSF 5-HIAA are associated with higher
      brain glucose metabolism in rhesus monkeys under standardized anesthesia.
      Aggressive nonhuman primates with low CSF 5-HIAA concentrations may have "innate"
      tolerance toward functional gamma-aminobutyric acid A receptor agonists such as
      pentobarbital, isoflurane, and possibly alcohol.

PMID- 8526247
TI  - Relationship of dissociation to self-mutilation and childhood abuse in borderline
      personality disorder.
AB  - OBJECTIVE: This study sought to document the prevalence of dissociative
      experiences in adult female inpatients with borderline personality disorder and
      to explore the relationship between dissociation, self-mutilation, and childhood
      abuse history. METHOD: A treatment history interview, the Dissociative
      Experiences Scale, the Sexual Experiences Questionnaire, and the Hamilton
      Depression Rating Scale were administered to 60 consecutively admitted female
      inpatients with borderline personality disorder as diagnosed by the Structured
      Clinical Interview for DSM-III-R Personality Disorders. RESULTS: Fifty percent of
      the subjects had a score of 15 or more on the Dissociative Experiences Scale,
      indicating pathological levels of dissociation. Fifty-two percent reported a
      history of self-mutilation, and 60% reported a history of childhood physical
      and/or sexual abuse. The subjects who dissociated were more likely than those who
      did not to self-mutilate and to report childhood abuse. They also had higher
      levels of current depressive symptoms and psychiatric treatment. Multiple
      regression analysis demonstrated that each of these variables predicted
      dissociation when each of the others was controlled for, and that self-mutilation
      was the most powerful predictor of dissociation. CONCLUSIONS: Female inpatients
      with borderline personality disorder who dissociate may represent a sizable
      subgroup of patients with the disorder who are at especially high risk for self
      mutilation, childhood abuse, depression, and utilization of psychiatric
      treatment. The strong correlation between dissociation and self-mutilation
      independent of childhood abuse history should alert clinicians to address these
      symptoms first while exercising caution in attributing them to a history of
      abuse.

PMID- 8526248
TI  - Attention deficit hyperactivity disorder and comorbid disorders: issues of
      overlapping symptoms.
AB  - OBJECTIVE: Since some symptoms are shared by both attention deficit hyperactivity
      disorder (ADHD) and comorbid psychiatric conditions, it is possible that a
      diagnosis of ADHD is an artifact of the overlapping symptoms. This article
      focuses on the assessment of the influence of overlapping symptoms on the
      diagnosis of ADHD. METHOD: Three groups of subjects were studied: a group of
      clinically referred children and adolescents, a group of nonreferred adults who
      were the parents of these children and adolescents, and a group of clinically
      referred adults with ADHD. The authors assessed the extent of symptom overlap
      between ADHD and the disorders that frequently co-occur with ADHD; major
      depression, bipolar disorder, and generalized anxiety disorder. To determine the
      degree to which this symptom overlap influences these diagnoses, each individual
      was rediagnosed on the basis of two different techniques that corrected for the
      overlapping symptoms, a subtraction method and a proportion method. RESULTS: The
      majority of subjects who had both ADHD and a comorbid psychiatric disorder
      maintained their diagnosis of ADHD when the overlapping symptoms were subtracted.
      Moreover, when overlapping ADHD symptoms were subtracted, on average, 79%
      maintained their diagnosis of major depression, 56% maintained their diagnosis of
      bipolar disorder, and 75% maintained their diagnosis of generalized anxiety
      disorder. CONCLUSIONS: These findings show that ADHD is not an artifact of
      symptoms shared with other psychiatric disorders and that the comorbid conditions
      themselves are not an artifact of overlapping ADHD symptoms.

PMID- 8526249
TI  - Abnormalities of regional distribution of cerebral vasculature in schizophrenia
      detected by dynamic susceptibility contrast MRI.
AB  - OBJECTIVE: The authors tested the hypothesis that the regional distribution of
      cerebral vasculature is anomalous in schizophrenia. METHOD: Dynamic
      susceptibility contrast magnetic resonance imaging was used to evaluate cerebral
      blood volume in the right and left occipital cortex, basal ganglia, and
      cerebellum of 10 subjects with schizophrenia and 10 healthy comparison subjects.
      RESULTS: Cerebral blood volume was greater in the schizophrenic subjects in every
      region studied. CONCLUSIONS: The findings suggest an abnormality of the
      configuration of cerebral blood vessels in schizophrenia.

PMID- 8526250
TI  - Interrater reliability of ratings of delusions and bizarre delusions.
AB  - OBJECTIVE: The authors evaluated the interrater reliability of ratings of bizarre
      delusions, addressing limitations of previous studies. METHOD: Fifty randomly
      selected psychiatrists rated bizarre delusions in 30 case vignettes adapted from
      a previous study by Spitzer and associates. Estimates of reliability were
      obtained for definitions of bizarre delusions in the DSM-III, DSM-III-R, and
      draft DSM-IV criteria for schizophrenia and for the clinicians grouped according
      to their current and previous experience with psychotic patients. RESULTS: The
      kappas for ratings of bizarre delusions according to the different definitions
      and among clinicians with different levels of experience were in the moderate to
      fair range. CONCLUSIONS: The reliability of ratings of bizarre delusions appears
      to be less than satisfactory for clinical practice, and the increased weight
      given to this symptom in modern diagnostic systems does not seem justifiable.

PMID- 8526251
TI  - Elevation of CSF somatostatin concentrations in mania.
AB  - OBJECTIVE: The aim of this study was to compare levels of CSF somatostatin
      (somatotropin release-inhibiting factor) in drug-free patients with different
      major psychiatric disorders. METHOD: CSF somatostatin concentrations were
      measured in 66 drug-free inpatients with Research Diagnostic Criteria diagnoses
      of schizophrenia, major depressive disorder, manic disorder, or schizoaffective
      disorder. RESULTS: In comparison with both the patients with schizophrenia and
      the patients with schizoaffective disorder, the manic patients had markedly
      elevated CSF somatostatin concentrations. The depressed patients had
      significantly higher levels than the schizophrenic patients. CONCLUSIONS: Mania
      is associated with relatively higher CSF somatostatin concentrations.

PMID- 8526252
TI  - Nonresponse to reinstituted lithium prophylaxis in previously responsive bipolar
      patients: prevalence and predictors.
AB  - OBJECTIVE: The authors explored the prevalence and predictors of nonresponse to
      reinstituted lithium prophylaxis in bipolar patients who had relapsed after
      discontinuation of successful lithium treatment. METHOD: The study was conducted
      with 54 bipolar patients for whom lithium had been reintroduced after one or more
      recurrences following discontinuation of successful prophylaxis. They were
      followed up, through bimonthly personal interviews, for 1 year after recovery
      from the episode during which lithium treatment had been resumed, or up to the
      first recurrence with onset after lithium reinstitution. RESULTS: During the
      follow-up period, 44 patients did not have any affective episodes, whereas 10 had
      at least one recurrence. The only significant difference between the two patient
      groups was the longer duration of prediscontinuation lithium treatment for the
      patients who relapsed. CONCLUSIONS: Nonresponse to reinstituted prophylaxis
      should be considered among the possible risks of the interruption of effective
      long-term lithium treatment.

PMID- 8526253
TI  - Lack of efficacy of clozapine monotherapy in refractory obsessive-compulsive
      disorder.
AB  - OBJECTIVE: The authors assessed the efficacy of clozapine monotherapy for adults
      with treatment-resistant obsessive-compulsive disorder. METHOD: Twelve adults
      with refractory obsessive-compulsive disorder participated in a 10-week, open
      label, systematic trial of clozapine. They were assessed with the Yale-Brown
      Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, and the global
      improvement item of the Clinical Global Impression (CGI) scale. RESULTS: None of
      the 10 patients who completed the trial was a responder. No significant change
      was observed in obsessive-compulsive or depressive symptoms or in scores on the
      CGI global improvement item. CONCLUSIONS: These findings suggest that clozapine
      monotherapy is not effective for most adult patients with treatment-resistant
      obsessive-compulsive disorder.

PMID- 8526254
TI  - Impact of cumulative lifetime trauma and recent stress on current posttraumatic
      stress disorder symptoms in holocaust survivors.
AB  - OBJECTIVE: The purpose of this study was to examine the relationships among
      cumulative lifetime trauma, recent stressful events, and presence and severity of
      current posttraumatic stress disorder (PTSD) symptoms in Holocaust survivors and
      nonexposed comparison subjects. METHOD: Lifetime trauma, recent stressful events,
      and presence and severity of PTSD were assessed in Holocaust survivors (N=72) and
      comparison subjects ( N=19). RESULTS: Survivors with PTSD (N =40) reported
      significantly greater cumulative trauma and recent stress than survivors without
      PTSD (N=32) and comparison subjects. Severity of PTSD symptoms, cumulative
      trauma, and recent stress were significantly associated. CONCLUSIONS: The
      presence and severity of current PTSD were related to having experienced
      stressful events in addition to the Holocaust.

PMID- 8526255
TI  - Low plasma homovanillic acid levels in recently abstinent alcoholic men.
AB  - OBJECTIVE: To explore dopaminergic mechanisms in alcohol dependence, the authors
      measured plasma homovanillic acid (HVA) in recently detoxified alcohol-dependent
      men. METHOD: Plasma HVA was measured in 83 male patients with a diagnosis of
      alcohol dependence who had maintained documented abstinence for at least 3 weeks
      and in 69 healthy male comparison subjects. RESULTS: The alcoholic patients as a
      group had significantly lower levels of plasma HVA than the comparison subjects.
      This difference was not influenced by any other measured covariate, including a
      family history of alcohol dependence. CONCLUSIONS: These results imply that
      factors such as alcohol dependence should be taken into account in future studies
      of plasma HVA.

PMID- 8526256
TI  - Further study of neuroleptic malignant syndrome.

PMID- 8526257
TI  - Self-administered exposure therapy by a Vietnam veteran with PTSD.

PMID- 8526258
TI  - Venlafaxine for treatment of obsessive-compulsive disorder.

PMID- 8526259
TI  - Final Exit and suicide assessment in a forensic setting.

PMID- 8526260
TI  - "Awakenings" effect with risperidone.

PMID- 8526261
TI  - Responses to mCPP stimulation in depressed patients.

PMID- 8526262
TI  - Responses to mCPP stimulation in depressed patients.

PMID- 8526263
TI  - Life-sustaining treatment preferences of the elderly depressed.

PMID- 8526264
TI  - Psychopathology and mental retardation.

PMID- 8526265
TI  - Long-term results of open meniscal repair.
AB  - The purpose of this study was to document the long-term clinical and radiographic
      results of open meniscal repair. Thirty consecutive patients, involving 33 open
      repairs, were evaluated by history, physical examination, KT-1000 arthrometer
      testing, Lysholm II score, Tegner activity score, and weightbearing radiographs.
      The mean followup was 10.9 years (range, 10.1 to 13). No patients were lost to
      followup. Seven meniscal retears (21%) were documented (six demonstrated by
      repeat arthroscopy and one suspected on clinical evaluation). Three of 21 (14%)
      acute repairs (performed within 6 weeks of injury) retore as compared with 4 of
      12 (33%) chronic repairs (P = 0.38). None of the 12 menisci in stable knees (< 3
      mm side-to-side difference in anterior laxity on manual maximum load testing)
      sustained retears, compared with 7 of 21 (33%) menisci in nearly stable or
      unstable knees (P = 0.03). Standing radiographs revealed no degenerative changes
      in 22 of 26 (85%) compartments with successful repairs as compared with 3 of 7
      (43%) compartments with retorn menisci (P = 0.04). We concluded that the long
      term survival rate of repaired menisci was 79%, that increased retear rates were
      encountered in unstable knees, and that radiographs provided evidence for the
      biomechanical function of successful meniscal repairs.

PMID- 8526266
TI  - A method to help reduce the risk of serious knee sprains incurred in alpine
      skiing.
AB  - The incidence of severe anterior cruciate ligament sprains was once only a third
      the current rate. This fact led the authors to believe a means to help reduce the
      risk of anterior cruciate ligament injury among skiers might be found. Using
      videotapes of the occurrences of anterior cruciate ligament sprains in alpine
      skiers and the data associated with more than 1400 anterior cruciate ligament
      injuries observed in a 22-year study, the authors identified two common
      mechanisms of anterior cruciate ligament injury. From this information, a study
      was designed to determine if training could help reduce the risk of anterior
      cruciate ligament sprains. During the 1993 to 1994 season, the on-slope staff
      from 20 ski areas participated in a training program involving viewing videotaped
      scenes where knee injuries occurred. Data from 22 ski areas, where staff were not
      exposed to the training, were assembled to form a control group. Data concerning
      anterior cruciate ligament injuries were collected from both groups for the three
      seasons 1991 to 1994. A total of 179 serious knee sprains were evaluated. Serious
      knee sprains declined by 62% among trained patrollers and instructors compared
      with the two previous seasons, but no decline occurred in the control group.

PMID- 8526267
TI  - Long-term followup of Bankart reconstruction. Incidence of late degenerative
      glenohumeral arthrosis.
AB  - We identified 52 patients (56 shoulders) who underwent Bankart reconstructions
      for recurrent anterior instability between 1970 and 1983. We wanted to determine
      the prevalence of late degenerative arthrosis of the glenohumeral joint. Thirty
      one patients (33 shoulders) returned for evaluation consisting of a
      questionnaire, physical examination, and radiographs, at an average 15-year
      followup. A true anteroposterior view and an axillary lateral view of both
      shoulders were obtained to identify signs of glenohumeral degenerative disease.
      The Bankart rating score devised by Rowe et al. was used to determine the
      subjective and objective outcome. The average Bankart score was 84. Average
      restriction of external rotation was 18 degrees with the arm at the side and 15
      degrees with the arm abducted 90 degrees. Radiographic evaluation showed that 13
      operated shoulders had normal radiographs, 14 had minimal degenerative changes, 3
      had moderate changes, and 1 had severe changes. The patient with severe
      degenerative changes had marked restriction of external rotation of his operated
      shoulder. Statistical analysis using Spearman correlation coefficients revealed
      that there was a relationship between degenerative radiographic changes and
      restriction of external rotation with the arm abducted 90 degrees and length of
      followup, although correlations were limited because of the small number of
      patients with degenerative changes.

PMID- 8526268
TI  - Arthroscopic findings after shoulder dislocation.
AB  - The purpose of this study was to evaluate prospectively the arthroscopic findings
      of the unstable shoulder, to provide insights into the causes and mechanisms of
      shoulder instability, and to establish a rationale for using special surgical
      procedures. Arthroscopic examination was performed on 212 patients who had at
      least 1 documented shoulder dislocation. Of these 212 patients, 184 (87%)
      patients had anterior glenoid labral tears, 168 (79%) patients had ventral
      capsule insufficiency, 144 (68%) patients had Hill-Sachs compression fractures,
      116 (55%) patients had glenohumeral ligament insufficiency, 30 (14%) patients had
      complete rotator cuff tendon tears, 26 (12%) patients had posterior glenoid
      labral tears, 14 (7%) patients had superior labrum anterior and inferior lesions.
      As this prospective study shows, multiple morphologic changes are associated with
      instability of the glenohumeral joint; there is no single cause for an unstable
      shoulder. Arthroscopic examination of the shoulder before surgery revealed a
      significant amount of information that would have been undetected without the aid
      of expensive diagnostic tools. For instance, the labrum and rim of the
      anteroinferior glenoid showed typical abnormalities corresponding to different
      entities of anterior instability.

PMID- 8526269
TI  - Acromioclavicular reconstruction augmented with polydioxanonsulphate bands.
      Surgical technique and results.
AB  - During a 5.5-year period, we treated 64 patients with acute acromioclavicular
      separations by surgical reconstruction. According to the classification of
      Rockwood and Matsen, 54 patients had type III lesions, 1 patient had a type IV
      lesion, and 9 patients had type V lesions. Both the coracoclavicular ligaments
      and the ligaments of the acromioclavicular joint were reconstructed. An
      additional ligamentous augmentation was performed using completely resorbable 5-
      and 10-mm polydioxanonsulphate bands. Forty-five patients (70%) were re-examined
      at 2 to 7.5 years after surgery (mean, 32 months). The results were good or
      excellent in 40 cases (89%). Forty-one patients (92%) achieved a range of motion
      with an abduction deficit of less than 20 degrees. Calcifications in the area of
      the coracoclavicular or acromioclavicular ligaments did not affect the final
      range of motion. Complications consisted of one subcutaneous infection, one deep
      infection, and one failure of the reconstruction. Augmenting the reconstruction
      with polydioxanonsulphate bands allowed an early functional postoperative
      treatment. With this procedure, patients do not require removal of an implant,
      and complications from breakage or migration of metal implants are avoided.

PMID- 8526270
TI  - Isolated closure of rotator interval defects for shoulder instability.
AB  - Fifteen patients noted at surgery to have an isolated defect in the rotator
      interval and no other pathologic abnormality underwent closure of the defect as
      an isolated procedure for recurrent instability symptoms. Intraoperative
      assessment of each of these shoulders after the closure demonstrated adequate
      stability, and no other stabilization procedures were performed. The average age
      of the patients was 24 years, and 10 of the 15 patients were women. Examination
      under anesthesia revealed increased inferior translation in all patients, as
      illustrated by at least a 1+ sulcus sign. The rotator interval defect averaged
      2.75 cm in width and 2.3 cm in height. The rotator interval defect edges were
      freshened and approximated (nine patients) or imbricated (six patients),
      depending on the anterior capsular laxity and the degree of glenohumeral joint
      translation possible. Followup averaged 3.3 years (range, 2.2 to 5.3), and all
      patients achieved either a good or excellent result using the American Shoulder
      and Elbow Surgeons evaluation scale and the Rowe rating scale. Although most
      patients with a defect in the rotator interval require a standard stabilization
      procedure as a supplement to closure of the defect, approximation or imbrication
      of the defect as an initial step at surgery may confer adequate stability in
      selected patients and obviate the need for formal capsular advancement.

PMID- 8526271
TI  - A prospective study of ankle injury risk factors.
AB  - Many factors are thought to cause ankle ligament injuries. The purpose of this
      study was to examine injury risk factors prospectively and determine if an
      abnormality in any one or a combination of factors identifies an individual, or
      an ankle, at risk for subsequent inversion ankle injury. We examined 145 college
      aged athletes before the athletic season and measured generalized joint laxity,
      anatomic foot and ankle alignment, ankle ligament stability, and isokinetic
      strength. These athletes were monitored throughout the season. Fifteen athletes
      incurred inversion ankle injuries. Statistical analyses were performed using both
      within-group (uninjured versus injured groups) data and within-subject (injured
      versus uninjured ankles) data. No significant differences were found between the
      injured (N = 15) and uninjured (N = 130) groups in any of the parameters
      measured. However, the eversion-to-inversion strength ratio was significantly
      greater for the injured group compared with the uninjured group. Analysis of the
      within-subject data demonstrated that plantar flexion strength and the ratio of
      dorsiflexion to plantar flexion strength was significantly different for the
      injured ankle compared with the contralateral uninjured ankle. Individuals with a
      muscle strength imbalance as measured by an elevated eversion-to-inversion ratio
      exhibited a higher incidence of inversion ankle sprains. Ankles with greater
      plantar flexion strength and a smaller dorsiflexion-to-plantar flexion ratio also
      had a higher incidence of inversion ankle sprains.

PMID- 8526272
TI  - Test-retest reliability of ankle injury risk factors.
AB  - Ligamentous instability, ankle muscle weakness, foot-ankle alignment, and
      generalized joint laxity may be predisposing factors for ankle ligament injuries.
      The purpose of this study was to examine the reliability of these risk factors
      before and after the season in healthy individuals and to determine if any
      significant differences developed during the athletic season (range, 12 to 16
      weeks). Twenty-one healthy college-aged athletes were tested for generalized
      joint laxity, anatomic alignment of the foot and ankle, ligamentous stability,
      and isokinetic strength of the ankle muscles. This study showed that generalized
      joint laxity, ankle ligamentous stability, and ankle strength measurements
      demonstrated high correlation coefficients (r > 0.75). The high correlation
      coefficients suggested reliable measures. Some of the range of motion
      measurements had lower correlation coefficients, which suggested more variability
      in these measurements. After establishing the reliability in 24 of the 28
      measurements with standardized methods, further work is underway to evaluate the
      role of these factors in inversion ankle sprains.

PMID- 8526273
TI  - Ligament stability two to six years after anterior cruciate ligament
      reconstruction with autogenous patellar tendon graft and participation in
      accelerated rehabilitation program.
AB  - We studied patients who participated in our accelerated rehabilitation program
      after anterior cruciate ligament reconstructive surgery to determine if they
      showed signs of patellar tendon graft stretching. This program initiated in 1987
      emphasizes early full hyperextension, early weightbearing as tolerated, and
      closed-chain functional activities with rapid return to sports when the patient
      has attained full range of motion, approximately 65% of strength, and has
      accomplished the running and agility drills prescribed. A total of 209 patients
      met the criteria of KT-1000 arthrometer followup at the time full range of motion
      (5 degrees/0 degrees/135 degrees) was attained and at 2 years or more after
      surgery. The KT-1000 arthrometer manual maximum difference between the
      reconstructed and normal knees was used as the indicator of change in the graft
      length. All patients completed postoperative subjective questionnaires. The mean
      KT-1000 arthrometer value was 2.06 mm (SD, +/- 2.2) at full range of motion and
      2.10 mm (SD, +/- 1.9) at more than 2 years of followup (P = 0.7961). The
      patients' subjective stability scores averaged 19.6 with 97% reporting no
      instability episodes. Based on our findings, we conclude that an accelerated
      rehabilitation program after this type of reconstruction does not affect long
      term stability as measured by the KT-1000 arthrometer.

PMID- 8526274
TI  - Allograft reconstruction of the anterior and posterior cruciate ligaments after
      traumatic knee dislocation.
AB  - Seven patients (average age, 26.3 years) with traumatic knee dislocations were
      retrospectively evaluated more than 2 years (average, 51 months) after having
      fresh-frozen allograft anterior and posterior cruciate ligament reconstructions.
      All patients were treated consecutively at an average of 9.6 days after injury.
      Two patients had arterial injuries and three patients had or developed common
      peroneal nerve palsy. Five patients had 20 additional injuries. All patients were
      enlisted in an early, aggressive physical therapy regimen with early protected
      weightbearing. Four patients required a manipulation under anesthesia for
      arthrofibrosis at an average of 16.8 weeks postoperatively (range, 6 to 33
      weeks). At followup, only one patient had significant pain, three patients had
      rare or occasional giving way, and all seven were able to return to school or to
      the workplace. The functional grading was excellent in three patients, good in
      three patients, and fair in one patient. No patient had a significant flexion
      contracture; the average flexion arc was 118 degrees (range, 105 degrees to 135
      degrees). Knee dislocation is a very traumatic injury, often resulting in a
      painful, dysfunctional knee. Anterior and posterior cruciate ligament
      reconstructions in young, active patients can minimize pain and optimize
      functional outcome. Arthrofibrosis is a common occurrence in these patients, and
      manipulation under anesthesia is frequently required.

PMID- 8526275
TI  - Effects of an accelerated rehabilitation program after anterior cruciate ligament
      reconstruction with combined semitendinosus-gracilis autograft and a ligament
      augmentation device.
AB  - Forty patients with anterior cruciate reconstructions using semitendinosus and
      gracilis autografts and a ligament augmentation device were reviewed at a minimum
      of 20 months postoperatively to determine if an accelerated rehabilitation
      program was detrimental to intermediate follow-up results. The rehabilitation
      program included immediate full weightbearing, using crutches as aids for 2 weeks
      only, and a Generation II rehabilitation brace set at full range of motion for 2
      weeks followed at 2 weeks by bicycle riding and strengthening exercises. Return
      to sports was allowed at 4 months for nonpivoting sports and at 6 months for
      level 1 sports involving pivoting. Thirty-seven patients were available for
      followup. At followup, three grafts were determined to be nonfunctional (KT-1000
      arthrometer testing indicating > 4 mm of side-to-side difference). The other 34
      patients had good or excellent results, with all returning to their preinjury
      levels of sport with a brace. Early accelerated rehabilitation after anterior
      cruciate ligament reconstruction with semitendinosus and gracilis tendon
      autograft and a ligament augmentation device does not seem to affect the results
      adversely. Results in this series were as good as or better than other series
      using the same reconstructive technique.

PMID- 8526276
TI  - Long-term followup of anterior cruciate ligament reconstruction using freeze
      dried fascia lata allografts.
AB  - We identified 79 patients who underwent arthroscopically assisted intraarticular
      anterior cruciate ligament reconstruction with freeze-dried fascia lata
      allografts and an additional lateral extraarticular reconstruction. We were able
      to contact 62 patients (79%) for follow-up evaluation at an average of 134.5
      months. Forty patients (51%) returned for objective evaluation. Lysholm scores at
      followup averaged 92.3 and Tegner activity scores averaged 5.1. Only four (6%) of
      the 62 patients contacted reported episodes of full giving way. Thirty (75%) of
      the 40 patients examined demonstrated 3 mm or less side-to-side difference on KT
      1000 arthrometer manual maximum evaluation. Forty-eight (77%) of the 62 patients
      were participating in sporting activities at final followup. No patient had
      evidence of graft rejection.

PMID- 8526277
TI  - Ski injury statistics, 1982 to 1993, Jackson Hole Ski Resort.
AB  - A retrospective analysis was conducted on injury statistics compiled over 12
      seasons, from 1982 to 1993 (2.55 million skier-days), at a Wyoming ski resort.
      The population at risk was determined by ticket sales per year. A total of 9749
      skiing injuries was indexed by anatomic region and severity according to
      diagnosis on initial evaluation. Injury rates were then analyzed as a function of
      time. The injury rate remained constant at 3.7 injuries per 1000 skier-days
      during the 12 seasons. The rate of lower extremity to upper extremity injury
      decreased from 4:1 to 2:1 during the study period (P < 0.03). The ankle injury
      rate also decreased with time (P < 0.04). Ulnar collateral ligament sprains make
      up 7% of all injuries. Knee sprains in general account for 30% of all injuries.
      The incidence of anterior cruciate ligament tears increased as a function of time
      (P < 0.04) and accounted for 16% of all skiing injuries during the study period.
      The medial collateral ligament sprain was the most common injury, making up 18%
      of skiing injuries. Forty-seven snowboard injuries from the 1992 to 1993 season
      are also presented. Our injury statistics mirror those currently reported in
      North America, except our data reflect a higher incidence of knee sprains.

PMID- 8526278
TI  - Treatment of osteitis pubis in athletes. Results of corticosteroid injections.
AB  - This study presents the results of treatment of osteitis pubis in 12
      intercollegiate athletes. Early in this series, athletes were treated with
      prolonged rest, oral antiinflammatory medications, and hip-stretching exercises.
      Of the nine athletes treated in this manner, only one resumed symptom-free
      activity after 16 weeks of therapy; eight remained symptomatic and subsequently
      received a corticosteroid injection (1 ml 1% lidocaine, 1 ml 0.25% bupivacaine,
      and 4 mg dexamethasone) into the pubic symphysis. Of these eight athletes, three
      returned to full participation within 3 weeks of injection, four required a
      second injection to alleviate their symptoms, and one was unable to resume
      athletic activities despite two injections and an inguinal herniorrhaphy. In
      recent years, we have recommended an injection if treatment. Three athletes
      received a corticosteroid injection when their symptoms did not resolve. All
      three returned to full athletic competition within 2 weeks of the injection. The
      results of our study suggest that a more rapid return to intercollegiate
      athletics can be achieved through the judicious use of corticosteroid injections.

PMID- 8526279
TI  - Instrumented measurement of patellar mobility.
AB  - To provide an objective analysis of medial and lateral patellofemoral laxity, we
      examined 94 uninjured athletic subjects and 22 patients with unilateral lateral
      patellar dislocation. We developed an instrument to measure the compliance of the
      medial and lateral patellar restraints. The instrument recorded the force
      displacement relationship as the patella was pushed medially and laterally.
      Subtracting the medial displacement from the lateral displacement at a given
      force level allowed the tester to assess the peripatellar soft tissue "balance."
      The results for both the 2.5- and the 5-pound tests were significant. Paired
      comparisons differentiated the three groups, with significant differences between
      control and affected (P = 0.0001), control and contralateral (P = 0.0036), and
      affected and contralateral (P = 0.0157) knees. The mean result of the lateral
      minus medial displacement test for our sample population of control subjects was 
      2.1 mm for the 5-pound test. A negative value in this test indicates that medial
      displacement exceeds lateral displacement. This finding was present in 81% of
      control subjects. In contrast, the mean result for the patients' affected knees
      was +3.2 mm for the 5-pound test. Using the value of 0.0 mm as the diagnostic
      determinant for peripatellar imbalance, we found a test sensitivity of 91% and a
      specificity of 81%.

PMID- 8526280
TI  - Arthroscopic findings associated with roof impingement of an anterior cruciate
      ligament graft.
AB  - Nineteen patients with roof impingement of an anterior cruciate ligament graft
      had their grafts inspected during second-look arthroscopy. The diagnosis of roof
      impingement was suspected from the clinical findings of an effusion, extension
      deficit, recurrent instability, or anterior knee pain. The diagnosis was
      confirmed when a portion of the tibial tunnel was anterior to the tibial
      intersection of the slope of the intercondylar roof on a lateral roentgenogram of
      the fully extended knee. During second-look arthroscopy the impinged anterior
      cruciate ligament graft had one or more of the following features: fractured
      bundles, guillotined remnants at the tibial insertion, parallel fragmentation of
      an uninterrupted graft, fibrous nodule, or an extrusion of graft material at the
      outlet of the notch. We hypothesize that these changes in the integrity of the
      anterior cruciate ligament graft are caused by mechanical injury from roof
      impingement. CLINICAL RELEVANCE. One should suspect that a patient with an
      effusion, extension deficit, recurrent instability, or anterior knee pain after
      an anterior cruciate ligament reconstruction may have roof impingement. A lateral
      roentgenogram in full extension is diagnostic if the tibial tunnel is anterior to
      the intercondylar roof. The surgeon should be aware that impinged grafts can have
      a variety of arthroscopic appearances in addition to the previously reported
      fibrous nodule or Cyclops lesion.

PMID- 8526281
TI  - Strength profiles and performance in Masters' level swimmers.
AB  - The purpose of this study was to profile shoulder, trunk, and thigh strength and
      shoulder range of motion in competitive Masters' level swimmers and to see if
      these variables were related to swimming performance. Twenty-four Masters' level
      swimmers (13 men and 11 women) were tested for isometric trunk flexion and
      extension, isokinetic knee extension and flexion, shoulder abduction, internal
      rotation, external rotation, and supraspinatus muscle strength; shoulder internal
      and external rotation range of motion; and 50-yard swimming time. Strength scores
      were adjusted for weight. The men were significantly stronger than the women in
      trunk extension and flexion. Shoulder range of motion, shoulder abduction
      strength, and thigh strength were equal for both the men and the women. The men
      were stronger than the women in internal and external shoulder rotation.
      Conversely, the women tested were significantly stronger than the men in the
      supraspinatus muscle test. The men were significantly faster than the women in
      the 50-yard swim. Inverse relationships existed between swimming time and trunk
      flexion, trunk extension, and shoulder internal rotation strength. Trunk flexion
      strength remained the only significant predictive variable of swimming time in a
      multiple regression analysis.

PMID- 8526282
TI  - The role of glenohumeral capsular ligaments in internal and external rotation of
      the humerus.
AB  - The purpose of this study was to define the relationship between internal and
      external rotation of the humerus and the lengths of the anterior and posterior
      components of the glenohumeral capsuloligamentous complex. Six cadaveric
      shoulders (with intact ligaments and humeri) were stripped of all muscles. Each
      shoulder was mounted in its correct anatomic position. The extent of internal and
      external rotation of the humerus was then measured 36 times (at 10 degrees
      intervals in a 360 degrees humeral cone of motion). One component of the
      glenohumeral capsuloligamentous complex was lengthened, and the humeral rotation
      was again measured 36 times. The process of lengthening was done by cutting the
      ligament and replacing it with a beaded chain and catches sutured across the
      joint. The process of lengthening each component was repeated in 12 combinations,
      each with a different anterior and posterior component length. Humeral rotation
      was measured 36 times using a specially designed goniometer. The length of the
      anterior component of the glenohumeral capsuloligamentous complex most affected
      external humeral rotation, and the length of the posterior component most
      affected internal humeral rotation. However, the lengths of both the anterior and
      posterior components shared in limiting rotation at a number of positions.

PMID- 8526283
TI  - Eccentric and concentric strength of the shoulder and arm musculature in
      collegiate baseball pitchers.
AB  - Many pitching injuries occur during deceleration of the upper extremity when the
      muscles of the shoulder and arm are acting eccentrically. Published information
      regarding eccentric muscular strength in baseball pitchers is nonexistent. The
      purpose of this study was to assess bilateral isokinetic eccentric and concentric
      muscular strength of the shoulder's external and internal rotator muscles and the
      elbow's flexor and extensor muscles in a group of collegiate baseball pitchers (N
      = 25). Isokinetic strength was assessed at 1.6, 3.7, and 5.2 rad/sec. Our
      findings indicate that the internal rotator muscles were always stronger than the
      external rotator muscles and that the concentric and eccentric external-to
      internal strength ratios ranged from 62% to 81%. The eccentric strength of the
      shoulder rotator muscles averaged 114% that of concentric strength. The
      concentric and eccentric elbow extension-to-flexion strength ratios ranged from
      71% to 110%; eccentric strength averaged 33% higher than concentric strength. No
      differences were noted between dominant and nondominant limbs for any of the
      strength measures or ratios. Clinically, the findings of this study can serve as
      a reference during the evaluation, rehabilitation, and conditioning of throwing
      athletes.

PMID- 8526284
TI  - Gamma irradiation: effects on biomechanical properties of human bone-patellar
      tendon-bone allografts.
AB  - Sixty 10-mm bone-patellar tendon-bone allografts from young human donors were
      placed into four test groups, a control fresh-frozen group and three fresh-frozen
      irradiated groups. The irradiated groups were exposed to 2.0, 3.0, or 4.0 Mrad of
      gamma irradiation. The specimens were tested to tensile failure. The initial
      biomechanical strength of fresh-frozen allografts was reduced up to 15% when
      compared with fresh-frozen controls after 2.0 Mrad of irradiation. Maximum force,
      strain energy, modulus, and maximum stress demonstrated a statistically
      significant reduction after 2.0 Mrad of irradiation (P < 0.01). Stiffness,
      elongation, and strain were reduced but not with statistical significance. A 10%
      to 24% and 19% to 46% reduction in all biomechanical properties were found after
      3.0 (P < 0.005) and 4.0 (P < 0.0005) Mrad of irradiation, respectively. After
      irradiation with a 4.0 Mrad dose, the ultimate load was below that of reported
      values for the human anterior cruciate ligament. It is clinically important to
      observe and document changes in human ligaments that result from currently used
      doses of gamma irradiation. The results from this study provide important
      information regarding the initial biomechanical properties of fresh-frozen human
      bone-patellar tendon-bone allografts after bacterial sterilization with gamma
      irradiation. The current accepted dose for sterilization is between 1.5 and 2.5
      Mrad. There appeared to be a dose-dependent effect of irradiation on all the
      biomechanical parameters studied. Four of seven parameters were found to be
      reduced after 2.0 Mrad of irradiation. Reductions were found in all parameters
      after 3.0 and 4.0 Mrad of irradiation.

PMID- 8526285
TI  - Sense and nonsense regarding palatal canines.

PMID- 8526286
TI  - Arch length related problems.

PMID- 8526287
TI  - Implant site development.

PMID- 8526288
TI  - Case report RS: guided tissue regeneration precedes tooth movement and crossbite
      correction.
AB  - This patient presented with a Class III malocclusion and an anterior crossbite.
      Although spaces were present distal to the mandibular canines, the alveolar
      ridges were greatly atrophied. New bone was acquired through guided tissue
      regeneration. The alveolar ridges were augmented, followed by successful
      orthodontic tooth movement and correction of the Class III relationship and the
      anterior crossbite.

PMID- 8526289
TI  - Early mixed dentition treatment: postretention evaluation of stability and
      relapse.
AB  - Twenty-five patients who underwent early mixed dentition treatment were evaluated
      during the following stages: pretreatment (early mixed dentition), phase 2 (early
      permanent dentition), and postretention (average of 9.5 years). All patients were
      treated with a removable passive lingual arch. The mandibular incisors were
      judged to have satisfactory alignment at phase 2 evaluation and had no further
      orthodontic treatment. Nineteen of 25 cases (76%) demonstrated clinically
      satisfactory mandibular alignment postretention. Intercanine width decreased in
      72% of the cases postretention and arch length decreased in 100% postretention.
      Intermolar width increased in 18 of 25 (72%) of the cases during treatment and
      remained stable in 17 of 25 (68%) of the cases. No predictors or associations
      could be found to help clinicians in determining the long-term prognosis of
      dental stability.

PMID- 8526290
TI  - The validity of maxillary expansion indices.
AB  - Numerous indices have been proposed to help the clinician decide how much
      maxillary expansion will be required to alleviate crowding. The purpose of this
      investigation was to examine the validity of Pont's index, Schwarz's analysis and
      McNamara's rule of thumb. Records of 40 patients (20 females and 20 males) were
      selected from 155 consecutive pretreatment records. The discrepancy between
      actual intermolar/interpremolar widths and the index-generated widths were
      correlated against measures of crowding, and linear regressions were computed.
      Statistical analysis revealed that (1) males had more significant correlations
      between arch width and crowing than females, (2) interpremolar widths were more
      strongly correlated than intermolar widths, (3) Pont's index and McNamara's rule
      of thumb overestimated required arch width by 2.5 mm to 4.7 mm and 2.7 mm to 3.7
      mm respectively, and (4) Schwarz's analysis overestimated interpremolar width by
      2.5 mm to 4.3 mm but was reasonably accurate for intermolar width in males. The
      results suggest that these indices potentially overestimate the arch expansion
      required to alleviate crowding.

PMID- 8526291
TI  - Reliability of the Bolton tooth-size analysis when applied to crowded dentitions.
AB  - The Bolton tooth-size analysis is widely taught and used in orthodontics.
      However, its reliability has not been documented. The purpose of this study was
      to evaluate the reliability of the analysis when performed with needle-pointed
      dividers and a Boley gauge. Four clinicians measured the teeth on 15 sets of
      casts with two instruments at two sessions. The measurements were used to
      calculate tooth-size excess. To evaluate the measurement error, the difference
      between the two analyses made by the same investigator on the same set of casts
      was calculated. More of the same-investigator analyses were significantly
      correlated when the Boley gauge was used than when the needle-pointed dividers
      were used. Between-investigator analyses revealed significant correlations for
      each measurement session with both instruments. Every investigator was found to
      have at least one measurement error for each analysis and with each instrument
      that was as large as a clinically significant result of a Bolton analysis. The
      results of this study demonstrate that clinically significant measurement errors
      can occur when the Bolton tooth-size analysis is performed on casts with at least
      3 mm of crowding. The Boley gauge demonstrated a higher frequency of
      significantly correlated repeated measures and thus may be somewhat more reliable
      for this analysis than the needle-pointed dividers.

PMID- 8526292
TI  - Age-related differences in mandibular ramus growth: a histologic study.
AB  - Histologic reconstructions of remodeling variations of the mandibular ramus are
      demonstrated. This is significant because morphogenic relationships between the
      ramus and corpus establish mandibular arch position. Ground and polished
      microscopic sections were obtained from the ramus of 30 well-preserved human
      mandibles, dental age 1 to 13 years. The distribution of the various types of
      endosteal and periosteal bone tissues and resorptive versus depository surfaces
      was recorded. Fourteen of the 30 specimens and the majority of the mandibles at
      all ages examined exhibited the classic pattern of deposition and resorption
      (Type A or classic pattern) described by Enlow. Nine mandibles followed a second
      variation (Type B or vertical variation) involving a gonial angle alignment
      change. Seven followed a pattern of deposition and resorption similar to what
      Bjork might have called a forward rotating pattern (Type C or rotation
      variation). The differences in these patterns are large enough to suggest that a
      common description of one pattern of remodeling for all mandibles is incomplete.
      Unfortunately, the process of mandibular growth and remodeling does not appear to
      correlate well with dental age and the basis for changes in patterns may be more
      complex than first imagined. If temporal differences exist, they are not related
      directly to dental development. In theory, the differences in pattern are great
      enough to influence the outcome of mandibular orthopedic treatment.

PMID- 8526293
TI  - Craniofacial growth differences between low and high MP-SN angle males: a
      longitudinal study.
AB  - Craniofacial growth was followed longitudinally in two groups of boys with low
      and high MP-SN angles. The purpose was, first, to reveal group differences in
      dimensional change, and second, to find whether such differences were associated
      with a group difference in mandibular growth rotation. Group differences in
      dimensional change were explained by a difference in matrix rotation of the
      mandibular corpus, especially in the 6- to 12-year period. In the 12- to 15-year
      period, matrix rotation was similar in the two groups and so were dimensional
      changes. Morphologically, dimensional group differences in the 6- to 12-year
      period were theoretically compatible with the fact that mandibular rotation was
      clearly more forward in the low angle than in the high angle group.
      Statistically, dimensional variables with significant group difference were
      correlated strongly with matrix rotation and, in most cases, non-significantly
      with intramatrix rotation.

PMID- 8526294
TI  - Shear/peel bond strength of repositioned ceramic brackets.
AB  - Improper orthodontic bracket position may necessitate bracket removal and
      rebonding to establish correct bracket position. This procedure is necessary to
      use efficient orthodontic mechanics. The purpose of the study was to investigate
      (1) the amount of bonding resin remaining on single crystal bracket bases
      following electrothermal debonding, and (2) the bond strength of rebonded single
      crystal ceramic brackets under different treatment conditions. The bases of
      debonded, single crystal ceramic brackets (n = 100) were inspected for resin,
      classified with an adaptation of the adhesive remnant index (ARI), and evenly
      assigned to four experimental groups (n = 25). Groups were (1) silane coupling
      agent, (2) heat plus silane coupling agent, (3) hydrofluoric acid plus silane
      coupling agent, and (4) heat plus hydrofluoric acid plus silane coupling agent.
      An additional group of brackets not previously bonded was used as the control (n
      = 25). The brackets were bonded to 125 fresh bovine teeth. A force was applied 1
      mm from the bracket-resin interface by a testing machine. The force measured in
      this experiment was shear/peel and the ratio of shear to peel was 0.53. The AI
      index showed 79% of the brackets had no resin on their bases. The shear/peel bond
      strnegth was significantly greater for the control group than all other groups (P
      < 0.01). Treatment of electrothermally debonded ceramic brackets with silane or
      heat plus silane resulted in bond strength greater than 9 MPa. The use of
      hydrofluoric acid significantly reduced the bond strength below 2 MPa.

PMID- 8526295
TI  - Longitudinal predictability of AF-BF value in Angle Class I patients.
AB  - AF-BF is a linear cephalometric measure of the anteroposterior jaw relationship
      in the sagittal plane. A retrospective, longitudinal study was made to determine
      the mean Caucasian American AF-BF values at ages 8 and 18 years for 30 male and
      32 female participants of the Bolton Growth Study. Mean AF-BF values (+/- s.d.)
      for males were 7.3 +/- 2.7 mm at 8 years and 6.5 +/- 4.2 mm at 18 years. Mean AF
      BF values (+/- s.d.) for females were 6.7 +/- 2.1 mm at 8 years and 5.2 +/- 2.9
      mm at 18 years. No significant difference was found between the mean AF-BF values
      for males and females at either age group (P < 0.05). The decrease in AF-BF mean
      values with increasing age both for males and females was statistically
      significant. The correlation (r) for the AF-BF values was 0.49 (P < 0.05) for
      females and 0.86 (P < 0.05) for males. With increasing age, the mean difference
      between ANB values for females was 1.40 +/- 1.60 and 1.10 +/- 1.40 for males. The
      correlation of ANB angle and AF-BF provides a clinically useful tool for the
      cephalometric assessment of anteroposterior sagittal discrepancies of maxillary
      and mandibular denture bases.

PMID- 8526296
TI  - A study of bite force, part 1: Relationship to various physical characteristics.
AB  - A new device for measuring and recording bilateral bite force in the
      molar/premolar region has been developed. Because this new device is elastic and
      conforms to the occlusal surfaces of the teeth, and because the sensing element
      is relatively comfortable, it is believed that experimental subjects are less
      reluctant to register true maximal forces than in earlier studies. Potential
      correlations of maximum bite force to gender, age, weight, body type, stature,
      previous history of orthodontic treatment, presence of TMJ symptoms (jaw motion
      limitation, clicking with pain, or joint pain), or missing teeth were studied in
      a sample of 142 dental students. The mean maximum bite force of the sample was
      found to be 738 N, with a standard deviation of 209 N. The mean maximum bite
      force as related to gender was found to be statistically significant, while the
      correlation coefficients for age, weight, stature, and body type were found to be
      low. Even so, all data scatterplots exhibited relatively positive relationships.
      Correlations of maximum bite force to an earlier history of orthodontic treatment
      or to the absence of teeth were not found. Subjects reporting TMJ symptoms did
      not exhibit a significantly different maximum bite force than subjects without
      symptoms.

PMID- 8526297
TI  - A study of bite force, part 2: Relationship to various cephalometric
      measurements.
AB  - Maximum bilateral bite force, determined in 129 dental students, was evaluated
      with regard to six skeletal and eight dental measurements acquired from
      conventional lateral cephalometric radiographs. Statistically significant
      correlations for three of the skeletal measurements were found. Maximum bite
      force increased with regard to decreasing mandibular plane/palatal plane angle
      and to decreasing mandibular plane angles. Maximum bite force increased with an
      increasing ratio of posterior facial height to anterior facial height.
      Significant statistical correlation for only one of the eight dental measurements
      was found: maximum bite force related directly with increasing maxillary and/or
      mandibular dentoalveolar heights, and unexpected finding.

PMID- 8526298
TI  - [Pulmonary carcinoma nowadays: notes on epidemiology, primary prevention, and
      therapeutic planning].
AB  - Among the solid malignancies, lung cancer is today the most common cancer in the
      world (850,000 new cases during 1990). Moreover, with an estimated increase of
      about 5 percent a year, it now represents the first cause of mortality for cancer
      in both sexes. The evidence of a close relationship between lung cancer and
      cigarette smoking was first pointed out by E. Graham in 1950. Since then, the
      responsibility of active cigarette smoking in determining lung cancer as well as
      that of nicotine causing addictiveness, have been assessed clearly. Nevertheless
      primary prevention, mainly through the campaign against cigarette smoking, has
      always faced great difficulties because it clashes with the economic power and
      interests of tobacco companies. Moreover the epidemiologic trends show a
      progressive increase of the disease with a silent epidemic-like worldwide
      diffusion, in close similarity to AIDS. So, more than 5 million new cases a year
      of lung cancer are expected to appear at the beginning of 2000. The primary
      prevention against the major factor of risk-the cigarette-is mainly based, in
      developed countries, through the following official measures: i) a heavy taxation
      on the finished goods; ii) the conversion of the tobacco growing to other crops
      and iii) the package-based health information for all tobacco products. On the
      other side, while waiting for new effective chemoprevention methods, the need of
      getting a true early clinical diagnosis of tumor is emphasised. Only by this
      means is it indeed possible to improve the rate of cure through performing
      conventional resections of those cancers which could be discovered in still
      limited clinical stage. In the same time, a strong effort for radically operating
      Stage III locally advanced cancers, is also attempted through the newer
      tracheobronchoplastic procedures as well as the other over extended resections
      done directly in the mediastinal area. The neoadjuvant radio and/or chemotherapy
      combined treatments preceding surgery are also of great clinical interest.
      Finally the active palliative support aimed at improving the quality of life in
      patients affected by incurable tumors, represents a fast developing clinical
      project where a great ethical meaning is pre-eminent above all.

PMID- 8526299
TI  - [Carotid thromboendarterectomy: personal experience and review of the
      literature].
AB  - Carotid endoarterectomy (CEA) is known to prevent cerebrovascular accidents.
      Between February 1987 and December 1993 we performed 97 CEA on 82 patients (62
      male and 20 female, median age 66 +/- 7.6 years) 95.1% reported previous
      hemispheric neurological accidents; 4.9% were asymptomatic. Operative indications
      for asymptomatic patients were high degree stenosis (> 70%) of the internal
      carotid artery and ulcerated plaques with a moderate degree (50%) of stenosis.
      Major events (transient ischemic attack and stroke) were recorded in 73.2% cases.
      Preoperative investigations consisted of Duplex scan, arteriography, and cerebral
      CT scan or NMR. Operative mortality was 2.06% (2 cases) and perioperative stroke
      was 5.1% (5 cases). The sensibility, sensitivity and accuracy of Duplex scan to
      detect ulcerated plaques was 88.7%, 85.2% and 87.5% respectively. At a median
      follow-up of 33 months (range 6-81 months) 74 (92.5%) patients are free of
      strokes whereas 1 patient died for stroke. In our series the annual incidence of
      stroke was 0.5%. Our results suggest that Duplex scan is a reliable exam to
      investigate the carotid axis and CEA is a safe operation that prevents future
      cerebrovascular accidents.

PMID- 8526300
TI  - [History of reconstruction following total gastrectomy].
AB  - Near a century after the first successful total gastrectomy for gastric cancer,
      the authors review the various technical proposals for digestive tract
      reconstruction following total gastrectomy. Following a classification based on
      duodenal circuit, on the viscerum employed and on the creation of pouches and/or
      anti-reflux mechanisms, pros and cons of the various classes of reconstructions
      are clearly depicted, suggesting the reasons that made Roux-en-Y esophago
      jejunostomy and jejunal interposition the most used reconstructive procedure in
      worldwide clinical practice.

PMID- 8526301
TI  - [Gastric leiomyoblastoma: report of our case load].
AB  - Leiomyoblastoma of the stomach is a rare nosological entity (0.3% of all gastric
      tumors). During the last 13 years, the authors observed 7 of such tumors. In this
      paper, our cases are presented: these are discussed (together with a revision of
      the literature), particularly focusing on anatomo-pathological, diagnostic and
      therapeutic problems.

PMID- 8526302
TI  - [Perforation in Crohn's ileitis and its impact on the natural history of the
      disease. Note 1. Pathogenic process of the event, its relationship with
      intestinal obstruction, and its immediate consequences].
AB  - The pathogenesis and consequences of perforation in Crohn's disease were studied
      in 175 patients submitted to surgery. Perforation occurred in 40 (23%) patients
      with ileitis or ileocolitis, always in the terminal ileum; so-called "free"
      perforation occurred in 1 patient, "limited" perforation in all the others.
      Perforation is always a consequence of a chronic intestinal obstruction caused by
      the stricture of the terminal ileum, which becomes absolute because of the
      blocking by solid intestinal content. It occurs in the borderline between the
      stricture and proximal dilated loop, where the fissures (typical of Crohn's
      ileitis) are stretched to the utmost and dilated by the hyperpressure and
      distension of the wall following ileal stenosis. Perforation in the peritoneal
      cavity is always free; its consequence is usually not a diffuse septic
      peritonitis but an abscess, because only a small amount of intestinal content
      leaks out. This happens because in the proximal occluded bowel, pressure
      decreases abruptly following the spilling of intestinal content, particularly of
      gas. The abscess fed by intestinal content enlarges and finally opens into a
      hollow organ or onto the skin, causing a fistula (internal or external). The
      rational therapeutic approach to perforation and its consequences (the infrequent
      diffuse septic peritonitis, or the more common abscesses and fistulas) is always
      and only ileal stenosis removal.

PMID- 8526303
TI  - [Acute non-calculous cholecystitis: rationale for absolute emergency
      cholecystectomy].
AB  - The authors report a case of biliary peritonitis in acute perforated alithiasic
      cholecystitis and they highlight the opportunity to consider the acute alithiasic
      cholecystitis as an absolute emergency, both for the pathogenetic prenits and the
      coon association with other pathologies that represent adjunctive risk factors.

PMID- 8526304
TI  - [Traumatic disease of the pancreas].
AB  - Authors report their own experience referring to 12 pancreas traumatic lesions
      and they analyse the most updated and controversial aspects of such pathology.
      Concerning clinical detection, in spite of better chances of diagnosis given by
      computed tomography, delays and diagnostic difficulties are still considerable,
      both pre-operatory especially in isolated closed traumas, and during laparotomy
      for the detection of the lesion and check-up of a possible wirsung section. In
      most cases pancreatic lesions are of lesser degree, belonging to the I and II
      stage according Lucas' classification and can be treated with an external
      drainage performance. We have no choice but such conservative approach in the
      more serious cases, whenever a ductal lesion exists, if the patient suffers from
      hemodynamic lability and it is worth reducing the time of the operation and
      hematic losses or in those cases where serious associated lesions exist which
      require a priority treatment. While body and tail lesions can be successfully
      treated with distal pancreasectomy technique, in serious cephalic traumas there
      is a limited experience and it doesn't exist a common view on the matter. In
      these cases we believe to be useful to perform resections only as the last
      chance, since we prefer to perform alternative operation such ad internal
      drainage on jejunal ansa or pylorus exclusion. This last operation seems to
      achieve better results in terms of morbidity and mortality.

PMID- 8526305
TI  - [Bladder hernia].
AB  - A case of bladder hernia in a 61 years old patient affected by benign prostatic
      hypertrophy is presented. Pre-operative diagnosis was made by cystography. After
      an adenomiomectomy of the prostate, the patient underwent the resection of the
      herniated bladder which gave the bladder its normal shape with only a slight
      reduction of its capacity. Inguino-scrotal bladder hernias are very rare;
      recognized predisponing factors are weakening of muscular and connective
      structures of the inguinal canal, and bladder hypotonia secondary to urethro
      prostatic obstruction. These hernias, according to the anatomical position of the
      hernial sac, bladder and peritoneum, are classified in paraperitoneal (most
      frequent), intraperitoneal and extraperitoneal. The typical symptom of this
      disease is the two-stage micturition: the patient after a first spontaneous
      voiding, presses the mass and voids again. Other than cystography, useful
      diagnostic means are urography and cystoscopy which may confirm the diagnosis and
      rule out associated urinary disease. The treatment consists of either simple
      reduction of the bladder hernia, if the hernia is small, or resection of the
      herniated portion of the bladder, if the hernia is large or is associated with
      other diseases (e.g. tumors). Bladder resection is then followed by closure of
      the bladder wall in two layers and by inguinal hernia repair.

PMID- 8526306
TI  - [Treatment of trigeminal neuralgia with electroacupuncture. Experience with 104
      cases].
AB  - The essential or secondary trigeminal neuralgia is a very frequent and invalidant
      disease. In this forms, the medical or surgical conventional therapies are often
      inadequate. In this study we evaluated the effects of the acupunctural therapy on
      104 patients (mean age 52.3 +/- 13 years) with idiopathic or secondary trigeminal
      neuralgia. Utilizing cycles of twelve sessions, the acupunctural treatment was
      performed with an electrostimulator on local points and a distance or on aching
      points, in the secondary forms. The results was evaluated on the basis of three
      parameters (reappearance of the symptomatology, absence of pain in months and
      preceding treatments) and was defined using this scale: very well, well, fair and
      null. In conclusion we can say that acupuncture is an elective treatment in all
      kinds of secondary tregeminal neuralgia, while, in the idiopathic form, its
      validity is conditioned by preceding medical treatments and by beginning of the
      disease.

PMID- 8526307
TI  - [Video-assisted venous surgery].
AB  - The use of intraoperative angioscopy, till now utilized exclusively in arterial
      surgery, is now used also in venous surgery. From January 1992 54 patients
      underwent to video-guided venous surgery: 23 cases of external valvuloplasty of
      the sapheno-femoral junction (EV-SFJ), 25 cases of hemodynamic correction of
      varicose veins (French acronyms CHIVA), 5 cases of high ligation plus long
      saphenous vein intraoperative sclerotherapy (HL-IS) 1 case of sub-fascial
      perforators interruption (SPI), the only extraluminal videoguided procedure. We
      have used 3 different video-angioscopes: a 1 mm monofibroscopy let in a 6 Fr
      Fogarty catheter, a disposable 2,8 mm colangioscope and a 2,2 mm operative
      angioscope. For the perforators interruption we have utilised the thoracoscope.
      EV-SFJ: the angioscopy has confirmed the presence of normal valvular cusps in a
      dilated vein wall in 21 cases, so excluding 2 patients from the planned
      treatment. At the end of the operation the angioscope has verified the reapproach
      of valvular cusps. CHIVA: the angioscopy has allowed to identify the exact points
      of the superficial venous system which should be interrupted, according to the
      Franceschi's theory. This procedure can avoid the technical errors due to
      intraoperatory misleadings of the duplex mapping. HL-IS: consists of a classic
      high ligation followed by long saphenous vein intraoperative sclerotherapy. The
      angioscopy has allowed a complete deconnection of the long saphenous vein from
      tributaries and perforators. Furthermore has facilitate the proportional
      distribution of the sclerosing agent along the long saphenous vein. SPI: the
      videoassistance have permitted the identification of the insufficient perforating
      veins reducing their surgical exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526308
TI  - [Internal hernia of the stomach through gastro-splenic ligament defect].
AB  - An internal hernia of the stomach through a gastro-splenic defect is presented.
      This exceptional condition, that we can include between abdominal internal
      hernias, induced an high bowel occlusion that needed of emergency surgical
      treatment. The dilatation of the stomach, the weakness of anchorage structures,
      its ability to rotation and the emptying kinetic activity posterior actually
      favoured the incarceration of a part of the posterior wall in a gastro-splenic
      defect. Detension, hernial reduction and suture of gastro-splenic defect resolved
      the case: no post-operative complications, the patient was discharged in eight
      post-operative day.

PMID- 8526309
TI  - [Technic of overlapping sphincter anal repair in the treatment of traumatic anal
      incontinence].
AB  - Faecal incontinence is an important disabling symptom in the affected patients.
      Classically, we divide faecal incontinence in two main types: neurogenic faecal
      incontinence and traumatic anal incontinence. Traumatic anal incontinence is due
      to causes damaging sphincteric mechanism directly. The aim of the present study
      was to evaluate the outcome of overlapping sphincter anal repair procedure in the
      management of traumatic anal incontinence. To this end we studied 27 patients
      with traumatic anal incontinence who underwent an overlapping sphincter anal
      repair procedure according to the method described by Parks and McPartlin in
      1971. Mean follow up was up three years and was based mainly both on clinical
      evaluation with anorectal exploration and manometric values carried out on a 6
      monthly basis. When the outcome was evaluated in terms of faecal continence our
      date were similar to those reported by Parks and Fang. In the subjects studied we
      haven't reported any major complications apart from one case of abscess, one case
      of wound's infection and one case of stenosis which were efficaciously treated.
      Our findings supported the view that overlapping sphincter anal repair procedure
      is the surgical approach of choice in the patients with traumatic anal
      incontinence.

PMID- 8526310
TI  - New insights into the mechanisms of myeloma-associated renal diseases.

PMID- 8526311
TI  - [Varicella-zoster virus pancreatitis in hematologic diseases].
AB  - We report four cases of varicella-zoster pancreatitis in immunocompromised hosts.
      All 4 patients presented a severe immunodeficiency because of chronic
      lymphoproliferative disorders (mainly lymphoma and Hodgkin disease) and long-term
      immunosuppressive therapy. Varicella zoster pancreatitis is a very unusual
      presentation of varicella-zoster infection. Few cases of pancreatitis occurring
      after bone marrow transplantation have been reported. All 4 patients presented
      with acute epigastric pain associated with transient elevation of serum amylase.
      The vesicular rash followed the presenting symptoms of severe abdominal pain by 8
      days. This clinical presentation, occurring in immunocompromised patients,
      defines a set of symptoms which should lead the physician to suspect varicella
      zoster pancreatitis, even in the initial absence of the characteristic skin
      vesicular eruption. Early institution of antiviral therapy seems mandatory.

PMID- 8526312
TI  - [Viral hepatitis C in chronic hemodialyzed patients in southern Tunisia.
      Prevalence and risk factors].
AB  - To define, the prevalence and risk factors of hepatitis C virus (HCV) a
      prospective and multicentre study was performed in 235 patients undergoing
      haemodialysis, the anti-HCV antibodies were evaluated using an immuno-enzymatic
      method (wellcozyme anti-HCV). The following parameters were obtained for all
      patients: time on haemodialysis, blood transfusion, liver enzymes (ALT, AST),
      others virus markers: HBV (HBs Ag, HBs Ab, HBc Ab) and HIV. Anti-HCV was positive
      in 86 patients (42%). There was a significant (p < 0.05) relationship between
      presence of anti-HCV antibodies and duration of haemodialysis (33 +/- 24 vs 20 +/
      19 months). No statistically significant difference was found with blood
      transfusion and the others parameters. In conclusion, the prevalence of HCV in
      our center of dialysis was high. The duration of dialysis seems to be the main
      risk factor.

PMID- 8526313
TI  - Significance of various factors in patients with functional dyspepsia and peptic
      ulcer disease in Greece. A comparative prospective study.
AB  - This prospective study was undertaken to evaluate the significance of factors
      such as age, sex family history, educational status, residence area, H pylori
      antral colonization, smoking, alcohol consumption, coffee and cola drinking in
      Greek patients suffering from functional dyspepsia (FD), duodenal ulcer (DU), and
      gastric ulcer (GU). The study groups were chosen among consecutive outpatients
      who had undergone an upper gastro-intestinal (GI) endoscopy during a ten-month
      period because of dyspepsia, and who completed a suitable questionnaire; 295
      patients aged 18-85 years (M: 185, F: 110) were finally included as follows: 54
      patients aged 18-80 years M: 21, F: 33) with FD, 166 aged 19-85 years (M: 117, F:
      49) with DU, and 75 aged 24-85 years (M: 47, F: 28) with GU. As controls for FD
      patients, 54 previously studied, healthy non-dyspeptic people, well matched for
      age and sex, were used. No differences were found between them and FD patients.
      On the contrary, we found that the 3 groups of patients differed significantly
      for age (p = 1.07 x 10(-3)) and sex (p = 1.67 x 10(-4)) distribution. There was a
      rather even age distribution and a discrete female predominance in the FD group.
      Positive family history for peptic ulcer disease (PUD) was found in 19% of
      patients with FD as compared with 48.2% (DU) and 37% (GU) (p = 4.84 x 10(-4)).
      Significantly more patients with PUD were smokers (p = 6.16 x 10(-3)) and alcohol
      drinkers (p = 1.84 x 10(-4)). H pylori antral colonization was found in 61% of
      patients with FD as compared with 74% (GU) and 85% (DU) (p = 8.65 x 10(-4)) of
      patients. Finally, factors such as educational level, area of residence, and cola
      drink consumption did not differ in the studied groups of patients.

PMID- 8526314
TI  - [Emergency admission in public hospitals in Ile-de-France].
AB  - In order to describe the population requiring an emergency admission in public
      hospitals in Paris Ile-de-France region, 7 358 hospitalization records were
      selected in a large morbidity data base. This sample is representative of
      emergency hospitalizations in the public hospitals of Paris-Ile-de-France region.
      There were slightly more women and patients were more often hospitalized in a
      hospital in their neighbourhood. Medical advice before going to hospital was
      rare. The mean length of stay was 9.5 days. The main pathologies leading to
      emergency hospitalizations were trauma and intoxication, pregnancy and delivery,
      and cardiovascular disease. The annual emergency hospitalization rate was 33 per
      1 000 for Paris-Ile-de-France inhabitants of all ages. Limits and advantages of
      the results are discussed.

PMID- 8526315
TI  - [Anatomo-clinical conference. Hopital Cochin. Case No 3 - 1995. Apropos of
      destructive oligoarthritis].

PMID- 8526316
TI  - [Interview with Moncef Zouali: What is going to happen tomorrow in the field of
      lupus anti-DNA antibodies?].

PMID- 8526317
TI  - [Giant hemangioma of the liver disclosed by fever and an inflammatory syndrome.
      Apropos of 3 cases].
AB  - Three cases of giant liver haemangioma were revealed by fever and biological
      inflammatory changes, which disappeared after resection of the haemangioma. These
      rare symptoms accompanying liver haemangioma may lead to misdiagnosis. Resection
      whenever possible results in the disappearance of symptoms. Anatomic necrotic
      changes inside the angioma seem to be the cause of these inflammatory patterns.

PMID- 8526318
TI  - Viral myocarditis: are we dealing with an autoimmune phenomenon?

PMID- 8526319
TI  - [Role of bisphosphonates in the treatment of tumoral osteolysis].

PMID- 8526321
TI  - [Splenic abscess].

PMID- 8526320
TI  - [Pharmacology in the elderly. Changes in the pharmacodynamic response to a given
      drug concentration and changes in mechanisms of regulation].

PMID- 8526322
TI  - [Actinomycotic abscess of the spleen].

PMID- 8526323
TI  - [Multiple splenic abscesses in a 42-year-old man. Uncommon manifestation of
      myeloma].

PMID- 8526324
TI  - [Wegener granulomatosis. Anatomoclinical study. Review of the literature].

PMID- 8526325
TI  - [Lichenoid eruption caused by mesotherapy].

PMID- 8526326
TI  - [Recurrent leg ulcers, intra-alveolar hemorrhage, perforation of the nasal
      septum: primary antiphospholipid syndrome?].

PMID- 8526327
TI  - [Native valve Staphylococcus lugdunensis endocarditis in a patient with
      lymphoma].

PMID- 8526328
TI  - [Bacillus licheniformis meningitis].

PMID- 8526329
TI  - [Chronic subdural hematoma and transient neurologic deficiency].

PMID- 8526330
TI  - [Munchausen syndrome. Case report of a "patient" above suspicion].
AB  - The authors, using a clinical case, tried to explain the Munchhausen syndrome
      from a psychopathological point of view and especially argued why it is so
      different from hysteria. They made the hypothesis that the Munchhausen syndrome
      corresponded to a perverted discourse (in a sense of psychoanalytical
      terminology) which would set in place the patient-doctor relationship in a
      perverted way.

PMID- 8526331
TI  - [Are beta-blockers really depressogenic?].
AB  - More than 25 years of the use of systemic beta-blockers in cardiovascular
      pathologies, but also in various other indications, have yielded a number of
      reports suggesting that these drugs was linked with the development of clinical
      depression. Some retrospective studies have been carried out with positive
      results, but the rare longitudinal prospective studies have failed to confirm the
      association between beta-blockers use and depression. Clinical, methodological
      and pharmacological problems may explain these discrepancies and are of great
      interest.

PMID- 8526332
TI  - [Multiple personality: diagnosis or mystification?].

PMID- 8526333
TI  - [Anti-hallucinatory coping strategies in schizophrenia].
AB  - Despite the effectiveness of antipsychotic drugs in schizophrenia, many patients
      continue to have persistent positive symptoms like hallucinations. It has
      provided new interest for coping strategies used by hallucinated patients.
      Therefore the aim of the study was to explore the existence of such strategies in
      50 schizophrenic patients defined by the presence of hallucinations. A specific
      questionnaire about coping strategies and a scale for the assessment of positive
      and negative symptoms were used. Our results showed that each patient developed
      at least one strategy, even rudimentary. Moreover, whenever the type of
      hallucinations, they developed specific coping strategies, most of the time
      logically used: they used them as much as they were efficace. So coping
      strategies should be taken into account for the clinical management of
      hallucinated patients. Learning of these strategies through behavioural and
      cognitive therapy could help patients suffering from resistant hallucinations.

PMID- 8526334
TI  - [Ambulatory care of depressed patients. Retrospective study of 60 patients
      hospitalized for an episode of major depression].

PMID- 8526335
TI  - [Designation of symptoms in mental disorder].
AB  - In the author's opinion, language and clinical facts in psychiatry are misused
      and it is hypothesized that many malfunctions of psychiatric practise are
      symptomatic. It is indeed very hard to modelise mental illness: what terms should
      be chosen and how should they be articulated? Considering the complexity of the
      relationship between language, ideas and memory, an empirical and experimental
      approach has been chosen; working out structures of concepts isomorphic to
      psychiatric reality, either from observed phenomena or from words. In our view,
      language skills are sufficient to build these sophisticated models, and language
      skills can be trained as can be trained sensorimotor skills. Experimenting
      psychiatric language in using their encyclopedic knowledge will allow staff
      members to teach themselves and will have a heuristic value in changing their
      beliefs about reality. These experiments have been undertaken for a year and an
      half, in a general psychiatry ward, in a ward for retarded and autistic adults
      and in a rehabilitation ward. Rigour and perseverance are required but these
      experiments seem particularly promising.

PMID- 8526336
TI  - [The act of prescribing: a shadow zone in psychiatry].

PMID- 8526337
TI  - [Current aspects of the use of clozapine in the Chalons-sur-Marne Psychiatric
      Hospital: intestinal occlusion with clozapine].
AB  - The authors report three cases--one of them lethal--of intestinal occlusion among
      30 patients treated with clozapine between 1991 and 1994 in Chalons-sur-Marne
      Psychiatric Hospital. The responsibility of clozapine seems to be linked with its
      potent anticholinergic property. The attention of prescriptors is necessary and
      the monitoring of the drug should not be limited to the hematologic aspect.

PMID- 8526338
TI  - Who is susceptible to cancers of the breast, colon, and prostate?

PMID- 8526339
TI  - Molecular genetics of colorectal cancer.

PMID- 8526340
TI  - The spectrum of mutations at the p53 locus. Evidence for tissue-specific
      mutagenesis, selection of mutant alleles, and a "gain of function" phenotype.

PMID- 8526341
TI  - Family history of cancer.

PMID- 8526342
TI  - Preventive clinical trials. An overview.

PMID- 8526343
TI  - An overview of considerations for the testing of tamoxifen as a preventive for
      breast cancer.

PMID- 8526344
TI  - Retinoids in cancer chemoprevention. Clinical trials with the synthetic analogue
      fenretinide.

PMID- 8526345
TI  - The potential application of finasteride for chemoprevention of prostate cancer.

PMID- 8526346
TI  - Strategies for colon cancer prevention.

PMID- 8526347
TI  - Indole-3-carbinol. A novel approach to breast cancer prevention.
AB  - The results show that all of the carcinogens, oncogenes, and tumor-associated
      viruses that we have studied profoundly affect the extent of 2- and 16 alpha
      hydroxylation in a prorisk direction. All of the dietary and biological responses
      associated with increased cancer risk decrease 2-hydroxylation and increase 16
      alpha-hydroxylation. Remarkably, although PAHs are reported to induce P450-1A1,
      we have found them to decrease 2-hydroxylation. Finally, using indole-3-carbinol
      to induce 2-hydroxylation results in the chemoprevention of mammary tumors in
      rodents and recurrences of laryngeal papillomas in humans. Also correlating with
      these studies in HPV is the decrease in the C-2/C-16 alpha metabolite ratio
      observed in women with CIN relative to control subjects. The greatest decrease
      was observed in women with the most severe form, CIN3 (Figure 23). These findings
      are under further investigation.

PMID- 8526348
TI  - Chemoprevention of colon cancer by dietary curcumin.

PMID- 8526349
TI  - Molecular markers in chemoprevention of colon cancer. Inhibition of expression of
      ras-p21 and p53 by sulindac during azoxymethane-induced colon carcinogenesis.

PMID- 8526350
TI  - Inhibition of DNA adduct formation of 2-amino-1-methyl-6- phenylimidazo[4,5
      b]pyridine (PhIP) by dietary indole-3-carbinol (I3C) in the mammary gland, colon,
      and liver of the female F-344 rat.

PMID- 8526351
TI  - Chemoprevention of mammary preneoplasia. In vitro effects of a green tea
      polyphenol.
AB  - The major findings of this study can be summarized as follows: (1) the c-myc
      oncogene-transfected and MTV-expressing mammary epithelial cells exhibit aberrant
      hyperproliferation in vitro preceding tumorigenesis in vivo; (2) upregulation of
      aberrant hyperproliferation (i.e., anchorage-independent growth) in initiated
      cells represents a cellular marker for preneoplastic transformation; (3) the tea
      polyphenol EGCG differentially downregulates aberrant hyperproliferation in myc
      oncogene- and MTV-initiated cells; (4) the present in vitro model provides an
      efficient assay for chemoprevention of mammary preneoplasia by naturally
      occurring compounds.

PMID- 8526352
TI  - Effect of retinoic acid (RA) in MNU-induced rat mammary tumors.

PMID- 8526353
TI  - Inhibition of steroid 5 alpha-reductase activity by aliphatic fatty acids.
      Candidates for chemoprevention of prostate cancer.

PMID- 8526354
TI  - Phenolic antioxidants induce UDP-glucuronosyltransferase in rat liver.

PMID- 8526355
TI  - Omeprazole coinduces multiple xenobiotic-metabolizing enzymes in the rat.

PMID- 8526356
TI  - Activity of maitake D-fraction to inhibit carcinogenesis and metastasis.

PMID- 8526357
TI  - Inhibitory effects of chlorophyllin on chemically induced mutagenesis and
      carcinogenesis.

PMID- 8526358
TI  - The association of polymorphic N-acetyltransferase (NAT2) with breast cancer
      risk.

PMID- 8526359
TI  - Ovarian cancer. A model system to study cancer genetics.

PMID- 8526360
TI  - Investigation of the possible role of WNT genes in human breast cancer.

PMID- 8526361
TI  - Developing a role for genetics within a cancer program.

PMID- 8526362
TI  - K-ras2 mutation spectrum, DNA aneuploidy, and epithelial cell proliferation in
      colorectal adenomas.

PMID- 8526363
TI  - Development of murine (OC-147) and human (H-106) monoclonal antibodies reactive
      with a 53-kDa ovarian tumor-associated antigen.

PMID- 8526364
TI  - A case-series study of p53 nuclear overexpression in early-stage stomach cancer.

PMID- 8526365
TI  - Epidermal growth factor receptor status correlates with cell proliferation
      related 18A2/mts1 gene expression in human carcinoma cell lines.

PMID- 8526366
TI  - Low-income, minority women. Barriers to cancer screening.

PMID- 8526367
TI  - Breast cancer in African-American families. Risk perception, cancer worry, and
      screening practices of first-degree relatives.

PMID- 8526368
TI  - Head and neck screening day for the community.

PMID- 8526369
TI  - Involving family physicians in education programs for cervical cancer screening.

PMID- 8526370
TI  - Adherence to colorectal cancer screening. A brief overview.

PMID- 8526371
TI  - Planning the next step. A screening promotion and nutrition intervention trial in
      the work site.

PMID- 8526372
TI  - The contributions of molecular biology to cancer epidemiology.

PMID- 8526373
TI  - Behavioral and social factors that predict participation in the Breast Cancer
      Prevention Trial.

PMID- 8526374
TI  - A clinician-friendly computer program for calculating breast cancer risk using
      the Gail and Claus models.

PMID- 8526375
TI  - Object Class Networks (OCNs) for interface-independent calculation with Gail and
      Claus models.

PMID- 8526376
TI  - Estrogen metabolite ratios and risk assessment of hormone-related cancers. Assay
      validation and prediction of cervical cancer risk.

PMID- 8526377
TI  - The Strang National High Risk Registry. A program for delivery of cancer risk
      information and a resource for research.

PMID- 8526378
TI  - Community physician willingness to refer cancer patients for treatment education.

PMID- 8526379
TI  - Early life affects the risk of developing breast cancer.

PMID- 8526380
TI  - Changes in serum bile acids in normal human subjects following the adoption of a
      low-fat diet.

PMID- 8526381
TI  - Modulation of tumor necrosis factor-alpha (TNF-alpha) toxicity by the pineal
      hormone melatonin (MLT) in metastatic solid tumor patients.

PMID- 8526382
TI  - Prospective study on the diagnosis and prognosis of lung cancer by using new
      simultaneously observed seromarkers.

PMID- 8526383
TI  - Psychosocial and ethical implications of defining genetic risk for cancers.
AB  - In summary, we need to provide fully informed consent regarding the hazards and
      the benefits of genetic testing and defining risk. This reflects the first
      ethical principle of autonomy. It is the responsibility of the counseling team to
      make sure that the individual is psychologically equipped to deal with the
      emotional distress that may result from testing. An undue burden must not be
      placed on someone and harm must not be inflicted. This is the second ethical
      principle of beneficence. Third, awareness of the potential problems of testing
      is extremely important. These issues are those of disclosure, insurance problems,
      and employment problems--the third ethical principle of confidentiality.
      Recommendations for screening guidelines, regardless of testing results, should
      be provided. It is important for women who are not gene carriers to know that
      they still need to go for screening. Lastly, we need to find ways to help
      individuals cope with their risk status, whether it is actual high risk or
      perceived high risk. Helping women to develop positive coping strategies and to
      adhere to screening is extremely important. As the Huntington's data indicated,
      over time, regardless of their risk levels, individuals do learn how to cope and
      adapt with the outcome of testing. Women and men need to learn how to live with
      their risk status so that the negative psychological sequelae will be minimized.

PMID- 8526384
TI  - Mammographic screening in women 40 to 49 years old.

PMID- 8526385
TI  - Can mortality from colorectal cancer be reduced?

PMID- 8526386
TI  - Changes in early detection of prostate cancer in the United States.

PMID- 8526387
TI  - What are the critical attributes for cancer chemopreventive agents?

PMID- 8526388
TI  - How can carcinogenesis be inhibited?

PMID- 8526389
TI  - The role of estrogen in mammary carcinogenesis.
AB  - The in vivo and in vitro studies conducted to examine whether E2 functions as an
      initiator or a promoter in mammary carcinogenesis can be summarized as follows:
      (1) Clinical and animal studies in vivo have shown a positive correlation of up
      regulation of E2 C16 alpha-hydroxylation with either the presence of or the risk
      for breast cancer, suggesting that this metabolic alteration may represent an
      early-occurring event in the multistep process of tumorigenesis. (2) The mammary
      tissue, target for carcinogenesis, exhibits cancer risk-dependent alteration in
      E2 metabolism in the rodent and human mammary explant culture model, indicating
      that E2 metabolites may directly influence the mammary epithelium. (3) The 16
      alpha-hydroxylated metabolite of E2, 16 alpha-OHE1, induces genotoxic DNA damage
      and aberrant hyperproliferation similar to that induced by chemical carcinogens
      in the rodent cell culture model. In preinitiated or fully transformed rodent or
      human cells, 16 alpha-OHE1 promotes the expression of transformed phenotype. (4)
      The initiator-mediated perturbation of E2 C16 alpha-hydroxylation in rodent and
      human mammary explant cultures is modulated by naturally occurring dietary
      constituents that are known to modulate rodent mammary tumorigenesis. (5) The
      observed effect of E2 on mammary tumorigenesis may be due in part to the
      generation of 16 alpha-OHE1, which functions as a weak initiator or a potent
      promoter of tumorigenic transformation in mammary epithelial cells. (6) The
      reaction of 16 alpha-OHE1 with the transcription factor ER is unique in that it
      can be irreversible and leads to aberrant gene expression.

PMID- 8526390
TI  - Determinants of dust and endotoxin exposure of pig farmers: development of a
      control strategy using empirical modelling.
AB  - Personal exposure to dust and endotoxin was measured among 198 Dutch pig farmers.
      For each participant 8-h measurements were made on 2 days, one in summer 1991 and
      one in winter 1992. Mean time-weighted average (TWA) exposure to dust was 3.0 mg
      m-3 (arithmetic mean, range 0.3-27 mg m-3) and mean TWA exposure to endotoxin was
      130 ng m-3 (arithmetic mean, range 6-1503 mg m-3). Empirical statistical
      modelling was applied to identify activities and farm characteristics associated
      with exposure. In a multiple least-squares regression analysis, aspects of
      hygiene and feeding were major characteristics associated with dust exposure.
      Flooring and feeding were predominant characteristics explaining variation in
      endotoxin exposure. Activities performed frequently, like feeding and
      controlling, cleaning activities and activities in which very active animals were
      involved, such as teeth cutting and ear tagging, were associated with exposure to
      dust and endotoxin. The models were used to set priorities for the development of
      control measures to eliminate the dust and endotoxin hazard of pig farmers.

PMID- 8526391
TI  - Exposure to acid anhydrides in three resin and one cushioned flooring
      manufacturing plants.
AB  - Acid anhydrides are reactive organic chemicals of low molecular weight which
      cause occupational asthma. No previous research on the relationship between
      exposure to these chemicals and respiratory sensitization and development of
      occupational asthma has been reported. A retrospective cohort study was carried
      out in four factories (three alkyd resin factories and one cushioned flooring
      factory) to investigate the nature of exposure-response relationships for
      sensitization to phthalic anhydride (PA), trimellitic anhydride (TMA) and maleic
      anhydride (MA). This paper describes the results of full-shift and task-specific
      exposure measurements. Exposure to PA was low in relation to the Occupational
      Exposure Standard (OES). The highest full-shift PA exposures occurred among resin
      operators in the resin factory that used solid PA as compared to other resin
      factories where liquid PA was used. Arithmetic mean exposure levels to TMA and MA
      in the resin factories were well below their respective OESs. Short-term high
      exposures occurred during loading of acid anhydrides into the reactors and
      sampling and testing of the resin. Relatively high full-shift exposure to TMA
      occurred in the cushioned flooring factory, although no high peak exposures were
      detected.

PMID- 8526392
TI  - Three-dimensional finite-element simulation of a turbulent push-pull ventilation
      system.
AB  - A finite-element formulation with penalty approach to enforce continuity is
      employed here to simulate the three-dimensional velocity field resulting from a
      simple push-pull ventilation configuration. An analytic expression for the length
      scale and a transport equation for turbulent kinetic energy are coupled with the
      momentum equations. A coaxial square hood and jet are arranged with cross-draught
      perpendicular to the common centreline. Numerical predictions of the velocity and
      turbulence kinetic energy fields are evaluated in the plane of symmetry with hot
      film anemometry, and smoke-wire flow visualizations. The agreement of the
      simulated jet trajectories with flow visualizations is reasonable, as are
      velocities. Predictions of turbulence kinetic energy are not as good,
      particularly near the hood face. Despite the limitations the numerical approach
      is useful in assessing the impact of cross-draughts on the push-pull arrangement.

PMID- 8526394
TI  - Workshop MMF: assessment of toxicity of man-made fibres, Paris, France, 3-4
      February 1994. Proceedings.

PMID- 8526393
TI  - Acetic aldehyde and formaldehyde in cutting fluids and their relation to irritant
      symptoms.
AB  - The objective was to study the formation of acetic aldehyde in cutting fluids and
      its relation to irritation of mucous membranes and the skin. Acetic aldehyde and
      formaldehyde were analysed in two large cutting fluid systems in an engineering
      industry. Samples were taken 1-5 times a week during a year. Concentration of the
      cutting fluid, leakage oils, pH, bacteria, yeast and fungi were analysed weekly.
      The occurrence of mucous membrane irritation was registered through
      questionnaires to the exposed workers. About 50 persons were exposed to each of
      the cutting fluids. The concentration of the aldehydes varied with time and
      between the cutting fluids. None of the analysed parameters could explain the
      variable concentration of aldehydes. Mucous membrane irritation was much more
      common in one of the systems, e.g. the prevalence of irritation in the nose was
      about 30-40% in workers exposed to a cutting fluid, while the corresponding
      prevalence was less than 10% in workers exposed to another fluid. The occurrence
      of symptoms was slightly associated with the concentration of aldehydes and pH of
      the fluid varied more in the fluid that caused most symptoms. A few measurements
      of ammonia indicated a higher concentration of ammonia in the fluid that caused
      most symptoms. It is concluded that irritation of mucous membranes and the skin
      may vary considerably between different cutting fluids of similar composition and
      use but the causal factor could not be determined in this study, but a variable
      pH and an increased concentration of ammonia may be indicators in this context.
      The concentration of acetic aldehyde vary with time and between cutting fluids
      with similar composition. A high variability may be an indicator of less stable
      cutting fluids. Better markers for the surveillance of cutting fluids needs to be
      developed as well as a health control programme.

PMID- 8526395
TI  - Chronic inhalation studies of man-made vitreous fibres: characterization of
      fibres in the exposure aerosol and lungs.
AB  - Inhalation studies were conducted to determine the chronic biological effects in
      rodents of respirable fractions of different man-made vitreous fibres (MMVFs),
      including refractory ceramic fibre (RCF), fibrous glass, rock (stone) wool and
      slag wool. Animals were exposed nose-only, 6 h per day, 5 days per week, for 18
      months (hamsters) or 24 months (rats). Exposure to 10 mg m-3 of crocidolite or
      chrysotile asbestos induced pulmonary fibrosis, lung tumours and mesothelioma in
      rats, thus validating the inhalation model with known human carcinogenic fibres.
      Exposure of rats to 30 mg m-3 of refractory ceramic fibres (RCF) also resulted in
      pulmonary fibrosis as well as significant increases in lung tumours and
      mesothelioma. In hamsters, 30 mg m-3 of RCF induced a 41% incidence of
      mesotheliomas. Exposure of rats to 30 mg m-3 of fibre glasses (MMVF 10 or 11) or
      of slag wool (MMVF 22) was associated with an inflammatory response, but no
      mesotheliomas or significant increase in the lung tumours were observed. Rock
      wool (stone wool: MMVF 21) at the same exposure level resulted in minimal lung
      fibrosis, but no mesotheliomas or significant increase in the lung tumours were
      observed. Fibre numbers (WHO fibres) and dimensions in the aerosols and lungs of
      exposed animals were comparable in this series of inhalation studies. Differences
      in lung fibre burdens and lung clearance rates could not explain the differences
      observed in the toxicologic effects of the MMVFs. These findings indicate that
      dose, dimension and durability may not be the only determinants of fibre
      toxicity. Chemical composition and the surface physico-chemical properties of the
      fibres may also play an important role.

PMID- 8526396
TI  - Biopersistence of man-made vitreous fibres.
AB  - Methods for the determination of biodurability of man-made vitreous fibres are
      reviewed. For mineral wools the first step was the preparation of respirable
      fibre fractions. Fibres were administered to rats by inhalation or by
      intratracheal instillation. After serial sacrifice their lungs were digested by
      low-temperature ashing or by hypochlorite. The total number of fibres per lung
      and the distributions of length and diameter were analysed by electron
      microscopy. This resulted in a bivariate distribution of fibres at the various
      sacrifice dates. If the logarithm of the number of fibres decreased approximately
      linearly with time after exposure then the elimination kinetics of fibres can be
      characterized by a half-time. The half-times were compared between various
      experiments with rats exposed to mineral wool samples. In summary good agreement
      was found for the elimination of fibres after long-term inhalation and
      intratracheal instillation whereas shorter half-times were found after short-term
      inhalation.

PMID- 8526397
TI  - Evaluation of the oncogenic potential of man-made vitreous fibres: the inhalation
      model.
AB  - A rodent inhalation model has been developed for the evaluation of the eoncogenic
      potential of man-made vitreous fibres. It is successful in delivering a
      quantified dose of well-characterized fibres to the lungs of rodents, and with it
      sufficiently high fibre aerosol concentrations were lofted to enable a maximum
      tolerated dose to be achieved. Fischer 344 male rats were exposed to a well
      defined rat-respirable aerosol at concentrations for MMVF of 30, 16 or 3 mg m-3,
      6 h per day, 5 days per week for 104 weeks with final sacrifice at 20% survival.
      A control group was exposed to filtered air. The high dose was chosen based upon
      a 28-day maximum tolerated dose study with refractory ceramic fibres (RCF). The
      fibre aerosol generation system lofted fibres without breaking, grinding or
      contaminating the bulk material. Exposure was by flow-past nose-only systems
      which provided fresh fibre in a laminar stream to each animal individually. The
      study was performed according to the Good Laboratory Practice regulations. Fibre
      count, fibre diameter and length distribution, aerosol mass and chemical
      composition were determined throughout the study. Interim sacrifices were
      performed at 3 or 6 month intervals for 24 months. At each sacrifice, full
      necropsy was performed, the accessory lobe removed for subsequent digestion to
      determine the fibre lung burden and the remaining lobes inflated with fixative
      for histopathological evaluation. The lungs were evaluated by a pathologist and
      graded for the degree of macrophage infiltration, bronchiolization, fibrosis and
      pleural thickening, and were also scored according to the Wagner scale. Lesions
      were evaluated according to the number of adenomas, carcinomas and mesotheliomas.
      The accessory lobe was digested by low-temperature plasma ashing and the number,
      size distribution and chemical composition of the fibres determined. This model
      provides a sensitive and reproducible method for evaluating existing and new
      fibres. A variety of different of ceramic, glass, rockwool and slagwood fibres
      have been evaluated with this model.

PMID- 8526398
TI  - Physical characterization of MMVF for risk assessment.
AB  - Size and other physical properties of MMVF play a central role in risk
      assessment. They can be affected by, for example, conditions during
      manufacturing, and preparation prior to administration to experimental animals or
      cells. It is suggested that a necessary requirement for stating that an
      experiment has been repeated should be documented evidence that: (i) the
      administered fibres are alike when analysed with not less than a minimum number
      of well-established methods on single fibre and on bulk sample level; and (ii)
      doses must be equal, and the fibre concentrations and sizes at the primary target
      tissue must be documented. Assessment of fibre toxicity and assessment of
      potential for exposure are equally important in the risk assessment process. The
      physics of fibrous dust release is described and methods for a priori assessment
      of exposure are classified into three levels depending on the analytical effort
      involved: (1) direct analysis of the fibrous bulk material; (2) bench-scale test;
      and (3) full-scale tests of prefabricated insulation material in a test room
      during standardized insulation work. For the first method, two approaches are
      investigated. One relates the size-dependent measures (the mass of fibres with D
      < 3 microns, the total length of fibres with D < 3 microns and the total number
      of WHO fibres per unit mass of fibres) and the other considers fractions (the
      fraction of total fibre length with D < 3 microns, the fraction of WHO fibre
      number, and the fraction of fibre number with D < 3 microns). The values of the
      size-dependent measures that are quoted span 2-4 orders of magnitude for the
      ranges of nominal diameter and GSD(D) considered, and show strong and similar
      dependence on GSD(D). The second group of measures, based on fractions only range
      up to 2 orders of magnitude and are almost independent on GSD(D) for nominal
      diameters ranging 2-4 microns. The combined effect on exposure of bulk fibre
      size, and of addition of oil and binder, should be assessed by the rotating drum
      dustiness test. The gold standard test of prefabricated MMVF products should be a
      full-scale simulation. The slope of the curve relating overall average product
      nominal diameter and airborne fibre concentrations on a log-log scale [Esmen et
      al., Am. ind. Hyg. Ass.J. 40, 108-117 (1979)] has been confirmed on a qualitative
      basis using model calculations, so that this relation can be used as a first
      estimate of changes in exposure due to changes in nominal diameter of bulk
      material.

PMID- 8526399
TI  - A review of inhalation toxicology studies with para-aramid fibrils.
AB  - The paper summarizes the results of inhalation toxicology studies associated with
      para-aramid (p-aramid) fibrils. The review is subdivided into two categories: the
      results of inhalation toxicity studies and mechanistic inhalation studies.
      Keratin-associated lesions were observed in the lungs of female rats following
      chronic exposure to high concentrations of p-aramid. These lesions were
      originally interpreted as cystic keratinizing squamous cell carcinomas (CKSCC).
      In recent years, this keratinizing lesion has been observed in the lungs of rats
      with greater regularity in numerous chronic inhalation studies following
      exposures to a variety of dusts. In an attempt to reach a consensus on an
      appropriate diagnosis for this lesion, an international panel of pathologists was
      convened to evaluate the morphological aspects of this lesion. The panel
      considered that the most appropriate diagnosis for this lesion was 'proliferative
      keratin cyst' (PKC), the biological potential of the PKC remains controversial,
      but it appears to be unique to the rat species and has little relevance for
      humans. Mechanistic studies with p-aramid have demonstrated that acute inhalation
      of high concentrations of fibrils produces a potent but transient pulmonary
      inflammatory and cell labelling response. The inhaled fibrils have low durability
      in the lungs of rats as evidenced by a progressive decrease in median fibre
      lengths with increasing residence time in the lung. In contrast, in a comparative
      study, size-separated chrysotile asbestos produced a sustained increase over
      controls in cellular proliferation responses of terminal airways, parenchyma,
      subpleural and mesothelial regions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526400
TI  - The durability and distribution of glass fibres in the rat following intra
      peritoneal injection.
AB  - Intra-peritoneal (IP) injection is being recommended as a means of assessing
      potential carcinogenicity of MMF following inhalation. Little is known of the
      behaviour of fibres in the peritoneal cavity or its relevance to the lung. This
      study considered both the biopersistence and the distribution of dose following
      IP injection of fibres. Biopersistence of fibres in the peritoneal cavity has
      been compared with that observed previously in the lung. Marked differences were
      found, with long fibres (> 20 microns) being more durable in the peritoneal
      cavity than in the lung. Breakage could not account for this finding, whereas
      differences in dissolution could. The behaviour of fibres and powders and their
      distribution in the peritoneal cavity following injection of different masses is
      reported. Distribution of dose depended on injection mass, with masses of < 1.5
      mg showing even uptake onto the surfaces of the peritoneal organs, and higher
      masses resulting in the development of nodules of injection material, free in the
      peritoneal cavity, or loosely bound to the peritoneum. With fine powder, some
      clearance was observed over the first 48 h after IP injection, but not with
      fibres. The findings on both durability and distribution of dose following IP
      injection have implications on the justification for the use of IP injections in
      assessment of potential carcinogenicity of fibres following inhalation.

PMID- 8526401
TI  - The in vivo biological activity of ceramic fibres.
AB  - The well-known health effects following exposure to amphibole asbestos have led
      to some concern about the potential for other fibrous materials to cause similar
      diseases. This paper presents a summary of some of the inhalation experiments
      conducted with ceramic fibres in both rats and hamsters at the Research and
      Consulting Company, Geneva. One ceramic fibre (designated RCF1) was tested in
      rats at four exposure levels, this fibre was also tested in hamsters. Three other
      fibres were only tested in rats at the highest level--30 mg m-3. The increased
      incidence of tumours in these experiments has been contrasted with the negative
      results obtained with glass or mineral wools. However, there is evidence that the
      ceramic fibres were longer than the glass fibres and that long ceramic fibres
      were retained in lung tissue to a greater extent. This is sufficient to explain
      the results without recourse to explanations based on chemical differences
      between fibres.

PMID- 8526402
TI  - Airborne fibre concentrations and lung burden compared to the tumour response in
      rats and humans exposed to asbestos.
AB  - The excess risk of tumours exposed to asbestos were previously compared with the
      results of rat inhalation experiments. It could be demonstrated that humans at
      the workplace suffer from a tumour risk at fibre concentrations which are 300
      times lower than those needed in the rat inhalation model to produce the same
      risk. However, the estimation of human risk was based on the study of workers at
      a chrysotile textile factory, whereas animal experimental results were related to
      exposure to amphiboles. Since for this comparison the risk of cancer due to
      exposure to amosite or crocidolite fibres at the workplace is of interest,
      quantitative exposure-response relationships for lung cancer and mesothelioma for
      the white workforce of South African amosite and crocidolite mines were
      discussed. On comparing the risk of lung cancer in this study with the risk of
      lung cancer for chrysotile textile workers, it can be concluded, that the risk of
      lung cancer and mesothelioma from crocidolite and amosite was higher than in the
      chrysotile textile factory. It could be also demonstrated, on the basis of a
      study of the lung burden of mesothelioma cases and of controls, that a
      significantly increased odds ratio of about 5 was established at amphibole
      concentrations of between 0.1 and 0.2 f micrograms-1 dry lung (WHO fibres longer
      than 5 microns from TEM analysis). On the other hand, carcinogenic response was
      observed at a fibre concentration 6000 times higher in animal inhalation
      experiments with crocidolite asbestos (SEM analysis of WHO fibres). As a result
      of these findings, it has been concluded that inhalation studies in rats are not
      sufficiently sensitive for the detection of hazards and risks to humans exposed
      to man-made fibres.

PMID- 8526403
TI  - Advantages and limits of in vivo screening tests.
AB  - Several methods have been proposed to ascertain the potential toxicity of man
      made vitreous fibres (MMVF) in animals. The most frequently used in vivo methods
      include inhalation (IH) (whole body and nose-only), intratracheal (IT)
      instillation, intrapleural injection-implantation and intraperitoneal (IP)
      injection. This report compares reports of studies using these methods in terms
      of their: (1) relevance to humans; (2) standardization of technique; (3)
      validation of method; (4) need for fibre preparation; (5) estimation of maximum
      tolerated dose; (6) determination of 'overload'; (7) exposure regimen; (8)
      pathology requirements; (9) quality control procedures; (10) extent and type of
      peer review; and (11) value of data for risk assessment. The results of this
      investigation showed that the inhalation method was clearly superior to the other
      exposure methods in all respects, although it is the most expensive. The
      intratracheal instillation method was considered a second choice, while injection
      implantation methods were fraught with scientific and practical problems and the
      data derived from studies using these techniques were considered of value only
      for the study of specific mechanistic issues.

PMID- 8526404
TI  - Proposal of a tiered approach to assessing and classifying the health risk of
      exposure to fibres.
AB  - The basis of a preventative health policy for humans against potential risks from
      chemical products is based on risk assessment leading to the classification and
      labeling of substances. However, the different existing classifications do not
      give an homogeneous framework that can be used in every country. Therefore, a
      tiered approach to assessing and classifying the health risk of exposure to
      fibres is proposed based on the EU Directive on carcinogens. The aim of this
      paper is to propose an algorithm for the risk assessment of existing and future
      fibres. Clearly chemically defined respirable fibres should be classified
      according to an algorithm based on a step-by-step procedure: a priori criteria,
      screening tests, long-term inhalation tests and epidemiological data (for
      commercial fibres). Then fibre-containing products should be labelled according
      to the classification of each type of fibre it contains, on one hand, and the
      ability of the product to release fibre in the air, on the other. The different
      tests listed in this algorithm, extensively discussed during the Workshop, are
      presented in detail in the following paper.

PMID- 8526405
TI  - Deposition of inhaled asbestos and man-made mineral fibres in the respiratory
      tract.
AB  - This paper reviews publications dealing with the deposition of fibrous particles,
      including asbestos and man-made mineral fibres, in the respiratory tract of man
      and experimental animals, particularly of the rat. The effects of fibre diameter
      and length on total, thoracic and alveolar deposition are discussed. Total
      deposition in the respiratory tract of the rat increases quite steeply with
      aerodynamic diameter (Dae) from about 20% at a Dae of 1 micron to 100% at a Dae
      of 5 microns. Deposition in the alveolar region reaches a peak of about 10% at a
      Dae of about 2 microns, which corresponds to an actual fibre diameter of about
      0.4 microns. For fibres with diameters greater than this, alveolar deposition
      falls rapidly. For example, long glass fibres with an actual diameter of 1.5
      microns or short glass fibres with an actual diameter of 3 microns are
      essentially non-respirable in the rat. The fate of fibres deposited in different
      regions of the respiratory tract of the rat is also discussed and the factors
      which predispose fibres either to remain in alveolar macrophages or to be
      transferred to the interstitium and pulmonary lymphatics. Finally, the
      distributions in the lungs of fibres administered by inhalation and by
      intratracheal instillation are compared, and the advantages and drawbacks of each
      method of delivery discussed.

PMID- 8526406
TI  - Statistical analysis of results of carcinogenicity studies of synthetic vitreous
      fibres at Research and Consulting Company, Geneva.
AB  - Five inhalation studies of synthetic vitreous fibres have recently investigated
      experimental tumorigenic responses to four different refractory ceramic fibres
      (RCF), two fibre glasses, one stone (rock) wool and one slag wool. Except for one
      RCF, the source materials were typical commercial products. Three studies
      included positive control groups exposed to chrysotile or crocidolite asbestos.
      The studies were conducted using state-of-the-art technologies for fibre size
      separation, fibre lofting and nose-only inhalation exposure. The target average
      fibre size was 20 microns long by 1 micron diameter. Hamsters exposed to a kaolin
      RCF yielded a mesothelioma rate of 38%, but no lung cancers. There were no
      tumours among the chrysotile-exposed hamsters. At the highest dose of 30 mg m-3
      in rat studies, the commercial RCF all produced significant numbers of lung
      tumours, and some mesotheliomas. The fourth RCF, which had been heat-treated to
      simulate an after-service fibre, did not produce a significant excess of lung
      cancers, but did produce one mesothelioma. A rat multi-dose experiment with three
      lower doses of the kaolin RCF yielded one mesothelioma among 379 rats, but no
      excess of lung tumours. The overall dose-response relation for lung cancer did
      not appear to be linear, consistent with the possibility of a threshold close to
      the Maximum Tolerated Dose. No insulation wool (glass, stone or slag) exposure
      group had a lung tumour rate that differed statistically significantly from the
      tumour rate for the respective concurrent control groups, sham-exposed to
      filtered air. There was no significant difference in the total tumour rates
      between the four insulation wool groups and the control animals, and no
      significant dose-response relation above the respective sham-exposed control
      tumour rates. The total lung tumour rates for rats in both chrysotile and
      crocidolite exposure groups were significantly raised. One animal in each
      asbestos-exposed group developed a mesothelioma, whereas no air control or
      insulation wool-exposed animal did so.

PMID- 8526407
TI  - Detection of mineral fibre carcinogenicity with the intraperitoneal test--recent
      results and their validity.
AB  - The general experimental design of intraperitoneal (i.p.) carcinogenicity studies
      with inorganic fibres in rats is described. In a current study, in addition to
      glass microfibres, size-separated fine respirable fractions of commercial
      insulation wools (MMVF-11 and MMVF-21) also induced mesotheliomas after i.p.
      injection of 0.4 x 10(9) fibres. These fibre samples were also tested in
      inhalation studies. A special glass fibre type (B-01), which is of interest
      because of its low biodurability, induced tumours with 25- and 50-fold higher
      doses. The i.p. model has been proved to be much more specific and sensitive for
      testing the carcinogenicity of inorganic fibres than the inhalation model.
      Objections to this conclusion are cited and discussed with alternative arguments.

PMID- 8526408
TI  - [Is molecular dermatology a realistic perspective for 2020?].

PMID- 8526409
TI  - [X-linked genodermatoses].
AB  - Chromosome X is one of the best genetically defined. Many disease loci are
      assigned to this chromosome, due to the peculiar mode of inheritance of X-linked
      disorders. Chromosome X undergoes X-inactivation in females. Recombination with
      chromosome Y occurs at pseudoautosomal regions. Some features of X-linked
      genodermatoses are a consequence of these phenomenons: variable expression,
      topography following Blaschko's lines. This can be seen in incontinentia
      pigmenti, focal dermal hypoplasia or hypohidrotic ectodermal dysplasia. Deletions
      at the pseudoautosomal region may cause contiguous gene syndromes. Hence
      ichthyosis with steroid-sulfatase deficiency may occur in association with
      various disorders. Transmitting females should be recognized by clinical
      examination or molecular studies, as this represents the main point in genetic
      counselling.

PMID- 8526410
TI  - [Inherited abnormalities of the epidermis caused by mutation of keratins].
AB  - The recent identification of keratin mutations as a cause of hereditary disorders
      of keratinization stresses the importance of an intact cytoskeleton of
      keratinocytes. Four disorders have reported to be caused by keratin mutations so
      far: epidermolysis bullosa simplex, bullous congenital ichthyosiform
      erythroderma, ichthyosis bullosa and epidermolytic palmoplantar hyperkeratosis.
      Molecular genetic diagnosis of keratin disorders is being introduced into the
      clinical routine and prenatal diagnosis is possible after 10 weeks of gestation.

PMID- 8526411
TI  - [Genetics of vitiligo].
AB  - There are several arguments suggesting that vitiligo is a genetically dependent
      disease. Certain animals have comparable pigment disturbances (Smyth chickens,
      C57BL/6J-mi(vit)/mi(vit) mice and B light mice). Genetic studies have
      demonstrated that certain genes are crucial for the development of vitiligo.
      Familial cases and cases reported in twins are further arguments. There is a high
      risk for both children and siblings of a subject with vitiligo. Several HLA
      studies have been reported. Most show sporadic association between vitiligo and
      certain HLA groups, but there is no clear and regular association with any of the
      class I or II alleles. Intrinsic melanocyte anomalies which persist in cell
      culture also favour the genetic theory. Vitiligo is probably a polygenetic
      disease, simultaneous alterations in several genes either causing he disease or
      increasing susceptibility. One speculation would be that one or more genes are
      responsible for premature death of melanocytes. Likewise, genes affecting
      melanocyte growth either directly or via paracrine factors (genes coding for the
      keratinocyte melanotrophic factor, for example), and the combined effects of
      genes controlling autoimmune phenomena could be involved. Despite formal proof
      that vitiligo is genetically dependent, and despite rapid progress in molecular
      genetics, the gene or genes directly implicated in this dermatosis remain to be
      identified.

PMID- 8526412
TI  - [Prenatal diagnosis of cutaneous genetic diseases by the study of fetal DNA].
AB  - There has been considerable progress in chromosome mapping and gene
      identification in several severe hereditary skin diseases, leading to changes in
      genetic counseling. It is now possible to propose antenatal diagnosis to couples
      at risk based on an analysis of foetal DNA from trophoblast biopsies performed as
      early as the 9th week of gestation. Antenatal can be made by direct analysis
      based on identifying the mutation known in the family at risk or on indirect
      analysis based on the linkage disequilibrium of the allele or alleles associated
      with the disease in the family at risk. This method has already been shown to be
      effective in recessive dystrophic bullous epidermolysis, lethal Herlitz's
      junctional bullous epidermolysis, bullous ichthyosiform hereditary erythroderma,
      von Recklinghausen's neurofibromatosis, tyrosinase negative oculocutaneous
      albinism, Gorlin's syndrome, anhidrotic ectodermic dysplasia and Menkes disease.
      These techniques will replace microscopic examination of ultrastructure in foetal
      skin biopsies performed at 20 weeks gestation. They can also be applied to
      diseases where the antenatal diagnosis now relies on enzyme function tests or DNA
      distribution. Improving genetic counselling in these diseases requires the
      identification of the implicated genes, identification of the causal mutations in
      the families at risk and development of genetic markers for these diseases.

PMID- 8526413
TI  - [Ehlers-Danlos syndromes. Clinical, genetic and molecular aspects].
AB  - The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue
      disorders that share the common features of skin hyperextensibility, articular
      hypermobility, and tissue fragility. Considerable clinical and genetic
      heterogeneity exists, and more than nine separate forms have been recognized.
      Recent advances in the molecular analysis of EDS have identify defects
      responsible for EDS VI (homozygous and compound heterozygous mutations in the
      lysyl-hydroxylase gene), EDS VIIA and EDS VIIB (mutations in the type I collagene
      genes), EDS VIIC (deficiency of procollagen N-proteinase), EDS IX (mutations in
      the MNK gene), and EDS IV (mutations in the type III collagen gene). Of the
      various types of Ehlers-Danlos syndrome the most severe is type IV (EDS IV).
      Early studies showed that fibroblasts from EDS IV patients secreted lower than
      normal amounts of type III procollagen (Pope et al., 1975). Later, the disease
      was linked to COL3A1, the gene encoding this protein. More recently, with the
      publication of full length cDNA and partial characterisation of the gene
      structure, detailed analysis of mutations in EDS IV patients has become possible.
      Nineteen different mutations in the type III procollagen gene have been reported
      in different families with EDS IV. Recent results support the hypothesis that in
      EDS IV, dominant inheritance should be assumed, in sporadic cases also, unless
      proven otherwise. Very little is known about the genetics or biochemicals defects
      responsible for the others EDS subtypes, but with the applications of the tools
      of molecular biology, analysis of these defects if now within reach.

PMID- 8526414
TI  - [Value of molecular biology methods for diagnosis in bacteriology].
AB  - Progress in molecular biology has led to the development of new tools for
      bacteriological diagnosis. Sporadic genes coding for virulence factors can be
      detected with highly specific genetic probes applied to cultured bacteria. Such
      genetic probes can also be used to specifically identified cultured bacteria
      whose general taxonomic classification is known. Another advantage of molecular
      genetics is the possibility that the cell culture step may not be needed,
      bacteria being identified directly in the sample specimen. Such techniques are
      particularly interesting to identify bacteria which are difficult to culture (for
      example: Borrelia burgdorferi, Chlamydia trachomatis) or which grow slowly
      (mycobacteria). The bacterial DNA must be isolated and amplified with an enzyme
      reaction. This is a critical step in the method: several positive and negative
      controls are required. When performed under optimal conditions, amplification
      techniques are excellent methods which can offer results similar to culture
      methods in culturable bacteria. Finally, molecular biology can be used to
      identify previously cultured bacteria for which there is no taxonomic
      orientation. Here the ribosome 165 DNA must be amplified and sequenced. The
      sequence is then compared with a data bank allowing classification. One could
      image future techniques applied to certain pathology samples for the detection
      and identification of bacteria without need for a culture step. However, direct
      microscope examination and bacterial culture remain the basic methods for
      bacteriologic diagnosis, the advantages and disadvantages of molecular biology
      leading to its use a complementary method for improving the quality of the
      diagnosis.

PMID- 8526415
TI  - [Genetic diagnosis of mycobacterium infections by polymerase chain reaction
      (PCR)].
AB  - Diagnosis is often difficult for mycobacteria because of the limitations of both
      direct microscopy and cell culture. Polymerase chain reaction (PCR), widely
      developed in microbiology, could provide major progress in the diagnosis of
      tuberculosis and atypical mycrobacterial diseases. Sensitivity rarely exceeds 80%
      and can be lower than 60% compared with traditional culture techniques. The
      specificity of tuberculosis PCR is rarely better than 97% so that the positive
      predictive value varies from 5 to 75% depending on the incidence of tuberculosis
      in the tested population (from 0.2 to 10%). The sensitivity of PCR compared with
      traditional culture varies from 2 to 90% depending on the laboratory. The
      proportion of false negative usually varies from 3 to 20%. Reliability should be
      improved with standardized simplified techniques, but quality control remains
      essential to validate the method in each laboratory. Current management
      strategies cannot be developed or changed solely on the grounds of PCR results.

PMID- 8526416
TI  - [Genetic bases of cutaneous tumors].
AB  - Carcinogenesis is a multigenic phenomenon where 3 prevailing types of genes are
      involved: oncogenes which stimulate the cell proliferation, tumor suppressor
      genes which act as inhibitors and metastagenes which contribute to the tumor
      progress. In animal models it has been shown that epithelial skin carcinogenesis
      proceeds stepwise: initiation, promotion, premalignant progression and finally
      malignant conversion. The oncogene c-H-ras and the tumor suppressor gene P53 are
      the genes whose involvement in these steps of epithelial skin cancers are duly
      established. Less experimental data are available concerning melanoma. the role
      of the oncogene N-ras, the tumor suppressor gene MTS-1 (encoding for protein p16)
      ans the metastagene nm 23 has recently be emphasized. Some cytogenetic
      abnormalities on chromosomes 1, 6, 9, 10, 11 and 17 have also been observed and
      incite to look for other genes potentially involved in the development of this
      tumor.

PMID- 8526417
TI  - [Skin and gene therapy. Hopes and realities].
AB  - Genetic therapy is developing rapidly in dermatology. Because they are highly
      accessible and can be cultured and grafted, skin cells are an excellent
      application for this still experimental therapeutic approach. There are several
      possible applications in skin diseases. In this review we discuss the techniques
      of gene transfer, experimental results and future perspectives as well as the
      limitations of this new therapeutic strategy.

PMID- 8526418
TI  - [Gene therapy applied to melanoma].
AB  - Cellular immunotherapy combined with genetic therapy, a new therapeutic approach
      to melanoma, is aimed at destroying the tumour by stimulating the organism's
      immune defences (indirect method) or by transfecting genes directly into the
      tumoural cells (direct methods). The first method is the most widely used for
      melanoma. Lymphocytes extracted from the tumour are transfected with genes
      capable of increasing their cytotoxic action in situ when reinjected (TNF,
      interleukin 2, interferon gamma). Likewise, immunostimulation by genetic therapy
      can be applied to tumour cells with transfection, notably cytokins or genes
      inducing antigen expression on the susceptible surface to modify the tumour
      cells' immunogeneicity. This method uses oligonucleotide nonsense sequences with
      suicide genes replacing a suppressor gene. Clinical trials for genetic therapy on
      melanoma are still in the pilot stage. This clinical evaluation must take into
      account the patient's quality of life and treatment costs.

PMID- 8526419
TI  - [Radiation-induced cutaneous carcinoma].

PMID- 8526420
TI  - [Verrucous carcinoma. Nosologic aspects, apropos of 4 cases].
AB  - INTRODUCTION: The nosology of verrucous carcinomas is a complicated problem. The
      name given to each manifestation may vary with localization. We report our
      findings in four cases with this skin disease. CASE REPORTS: Four patients, 76,
      52, 76 and 55 years of age, presented with verrucous carcinoma. In the first
      case, the disease began with a chronic varicose ulceration localized on the
      anterolateral aspect of the right leg. In the second, the lesion was localized on
      the lateral aspect of the right leg facing a zone showing signs of repeated
      microtraumatisms. HPV-18 was isolated in this patient. The third case had a
      vegetating lesion on the dorsal aspect of the right hand, simulating a wart. The
      fourth case is a historic case in which a voluminous tumour developed over
      several years on an ulceration of the medial aspect of the left malleole,
      associated with trauma and venous insufficiency. COMMENTS: The three recent cases
      did not raise any particular problem with diagnosis. The diagnosis in the
      historical case, published in 1969 as a vegetating pyoderma, was corrected later.
      This illustrates the nosology problems raised in this particular form of
      epidermoid carcinoma which often has an impressive clinical presentation and a
      reassuring histology. The group of verrucous carcinomas include different skin or
      mucosal lesions formerly designated as oral florid papillomatosis, Buschke
      Lowenstein acuminate condyloma or pseudo-epitheliomatous vegetating pyoderma.
      Cuniculatum epithelioma was added to this group for simplification although this
      rarely observed lesion is a separate entity. CONCLUSION: The pathology diagnosis
      of verrucous carcinoma requires large and deep biopsy. Treatment is surgical and
      regular follow-up is needed as for all malignant tumours.

PMID- 8526421
TI  - [Spontaneous course of lesions of Leishmania major cutaneous leishmaniasis in
      Tunisia].
AB  - INTRODUCTION: The evolution of zoonotic cutaneous leishmaniasis (ZCL) caused by
      L. major, was usually described with crosssectional studies of patients under
      anti-leishmanial drugs. This work aimed to describe the clinical and
      parasitological status by a follow-up study of patients with ZCL and treated with
      a placebo. MATERIAL AND METHODS: In 1992, 58 patients with unique lesion of ZCL
      confirmed parasitologically and treated with vaseline twice a day for 15 days
      were followed in days 0, 15, 45 and 105. During every visit we have performed a
      clinical description of the lesion, a direct smear and a culture on NNN medium.
      RESULTS: 81 p. 100 of the lesions were ulcerated in day 0. A rapid clinical
      healing was noticed in 6.9 p. 100 of patients and the lesion remained active in
      25.9 p. 100 of cases until day 105. Direct smears became negative among 56.4 p.
      71 p. 100 and 92.3 p. 100 in days 15, 45 and 105 respectively. DISCUSSION: The
      ulcer was the most frequent sign during the diagnosis. The rapid conversion of
      positive parasitological tests suggest that the diagnosis of ZCL in endemic zones
      should be based mainly on clinical criteria.

PMID- 8526422
TI  - [Immunoglobulin G subclass distribution of anti-intercellular substance
      antibodies in pemphigus].
AB  - INTRODUCTION: The purpose of this study was to analyze the IgG subclass
      distribution of pemphigus anti-epithelial cell surface (ECS) antibodies and to
      determine whether it differs according to clinical features. MATERIALS AND
      METHODS: 25 skin biopsies and 16 serum samples, obtained from 27 cases of
      pemphigus, were analyzed by direct and indirect IF staining, with mice anti-human
      IgG subclasses monoclonal antibodies. RESULTS: IgG1 deposits were observed in 21
      of 25, IgG2 in 2, IgG3 in 0, and IgG4 in the 25 biopsies. IgG1 anti-ECS anti-ECS
      antibodies were detected in all 16 sera, IgG2 in 1, IgG3 in 1, and IgG4 in 15
      sera. The anti-ECS IgG subclass distribution does not differ according to the
      clinical parameters studied. DISCUSSION: The isotypic restriction to IgG1 and
      IgG4 subclasses, observed in this study, is similar to previously reported
      results. The heterogenous distribution and the small number of the studied
      samples did not allow to put in evidence a correlation with the clinical
      parameters.

PMID- 8526423
TI  - [Chronic urticaria and autoimmune thyroid diseases].
AB  - INTRODUCTION: Chronic urticaria results from multiple interactive causes. For
      certain authors dythyroidism is significantly more frequent in patients with
      chronic urticaria, often associated with other autoimmune disorders. PATIENTS AND
      METHODS: This study included 45 patients with chronic urticaria (29 men and 16
      women, mean age 45.6 years). All underwent clinical examination for thyroid
      disease with assay of free T3 and T4, ultrasensitive TSH and antimicrosome and
      antithyroperoxidase antithyroid antibodies. RESULTS: Among the 45 patients, 8,
      all women, had an autoimmune thyroid disease: Graves' disease (n = 1), juvenile
      chronic thyroiditis (n = 1), autoimmune disease n = 6). All had goiter but most
      had no clinical sign suggestive of hypothyroidism or hyperthyroidism. Other
      clinical features or laboratory findings suggested autoimmune disorders in 3.
      DISCUSSION: These results suggest that a complete thyroid examination with
      hormone assay, especially in women, should be performed in patients with chronic
      urticaria. TSH and antiperoxidase antibodies appear to be the most sensitive and
      specific assays in patients with autoimmune thyroid disease.

PMID- 8526424
TI  - [Ultrastructural localisation of pemphigus vulgaris and pemphigus foliaceus
      antigens by indirect immunoelectron microscopy. Apropos of 7 cases].
AB  - INTRODUCTION: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune
      blistering diseases characterized by loss of cell-cell adhesion and by
      autoantibodies directed against epidermal cadherins. The ultrastructural
      localization of PV antigen remains controversial, whereas the location of PF
      antigen seems to be established. The use of different techniques could explain
      these various data. To investigate this matter, indirect immunoelectron
      microscopy (IEM) and Western blot analysis on bovine tongue epithelium were used.
      MATERIAL AND METHOD: Serum samples from patients with PF(3), PV (4) and control
      samples from healthy patients (2) were analysed in this study. The inclusion
      criteria were based upon characteristic clinical features, level of epidermal
      cleavage on histological preparations and presence of circulating anti-epithelial
      cell surface antibodies. Indirect IME was performed on normal human skin.
      Peroxidase labelling was used. Serum samples were also analysed by western
      immunoblotting on bovine tongue epithelium. RESULTS: Indirect IEM examination of
      PV sera showed immune deposits located both on desmosomal and extra-desmosomal
      areas, whereas in PF, IgG deposits were strictly localized on desmosomal
      structures. By Western blot analysis, PV sera recognized a 130 kDa polypeptide
      and PF sera a 150 kDa polypeptide. DISCUSSION: Indirect IEM on normal human skin
      using peroxidase labelling was used because of the best antigenic conservation
      obtained. Our results suggest that PV antigen could exist both on desmosomal
      junctions and adherens junctions, whereas PF antigen (desmoglein I) is restricted
      to desmosome.

PMID- 8526425
TI  - [Darier's erythema annulare centrifugum of neonatal onset with a 15 years' follow
      up. Efficacy of interferon and role of cytokines].
AB  - INTRODUCTION: Darier's erythema annulare centrifugum (EAC) is a disease of
      unknown etiology. Some observations of EAC in infancy suggest a better prognosis
      for early EA. The observations presented herein gives different information
      regarding prognosis and pathogenesis. OBSERVATION: A child presents with typical
      lesions of EAC from early infancy up to the age of 15 years. Laboratory data are
      normal. Similar lesions were locally reproduced by intradermal injection by
      candidine but antifungal drugs were unsuccessful. Many antiinflammatory
      treatments failed to improve the disease. Because of the improvement during
      hyperthermic episodes, a treatment by subcutaneous interferon alpha (2 millions U
      3 times a week) was given for six months with a dramatic success (with seric
      increase of TNF alpha and IL2) DISCUSSION: The long term duration of EAC suggests
      that EA of infancy may represent the early beginning of Darier's EAC. The
      efficacy of interferon suggests that cytokines are involved in the pathogenesis
      of EAC.

PMID- 8526426
TI  - [Congenital pachyonychia, neurofibromatosis and sensory-motor polyneuropathy].
AB  - INTRODUCTION: A 71-year-old man consulted because he could not walk due to spots
      of hyperalgic, invalidating plantar keratodermia. A nearly identical
      symptomatology was observed in several members of the family suggesting an
      autosomal dominant hereditary disease due to painful callosities as described by
      Roth in 1978. CASE REPORT: The patient had pachyonychia on all fingers and toes,
      only the ring fingers and the fifth toes were not involved. Multiple epidermoid
      follicular cysts were also found on the trunk suggesting the diagnosis of type II
      hereditary pachyonychia or Jackson-Lawler disease. Axonal polyneuropathy was also
      found with cutaneous signs of neurofibromatosis. Cytology studies were performed
      in order to elucidate the relationship between these different findings. It was
      not possible to retain the diagnosis of complex axonal polyneuropathy as
      described by Tolmie where autosomal dominant inheritance of early onset ungueal
      dystrophy is associated with punctuated palmoplantar keratodermia and hereditary
      sensoromotor axonal neuropathy. CONCLUSION: This patient presented several types
      of complex neurocutaneous manifestations which could not be successfully related
      to each other.

PMID- 8526427
TI  - [Angiokeratoma and fucosidosis. Immunohistochemical and ultrastructural study].
AB  - INTRODUCTION: Angiokeratoma can lead to diagnoses other than Fabry's disease. We
      report a case of angiokeratoma in a child with fucosidosis. CASE REPORT: A 7-year
      old child with psychomotor retardation presented angiokeratoma located on the
      penis. Uptake of type I Ulex Europaeus Agglutinin antilectin antiserum was
      intense in the endothelial structure. This antibody is specific for alpha-L
      fucose residues which were thus found in large quantities in the vacuoles of the
      ultrastructure. The patient also had a major deficiency in leukocyte, serum and
      fibroblast alpha-fucosidase. COMMENTS: This is a typical case of fucosidosis, a
      rare hereditary disease with autosomal recessive transmission due to generalized
      deficiency in alpha-L-fucosidase. Diffuse angiokeratosis should suggest, other
      than Fabry's disease, fucosidase and other enzyme deficiencies including
      sialidase, GM1 gangliosidase as well as Kanzaki's disease.

PMID- 8526428
TI  - [Post-Herpes Zoster calcinosis].
AB  - INTRODUCTION: Cutaneous calcinosis, without any disturbance of phosphocalcic
      metabolism, secondary to circumscribed previous skin lesions are quite common.
      Those secondary to viral skin lesions are rare and worth of publication. CASE
      REPORT: A 73-year old female patient disclosed progressive calcinosis in the scar
      of a cervico-thoracic herpes zoster which occurred 20 years ago. DISCUSSION: The
      occurrence of a secondary calcinosis in an old scar is common and non specific:
      the eliciting role of a previous herpes virus infection (VZV) may be discussed in
      the reported case and in few other cases reported in the literature (HSV, CMV)

PMID- 8526429
TI  - [Case for diagnosis. Streptococcus group A proctitis].

PMID- 8526430
TI  - [Case for diagnosis. Histoid leprosy].

PMID- 8526431
TI  - [Polymyositis and dermatomyositis. Current status].

PMID- 8526432
TI  - [Complications from silicone implants and other so-called inert materials].

PMID- 8526433
TI  - [Linear porokeratosis].

PMID- 8526434
TI  - [Should plantar warts be aggressively treated?].

PMID- 8526435
TI  - [Current attitude to severe acute digestive hemorrhage caused by rupture of
      esophageal varices in cirrhotic patients].

PMID- 8526436
TI  - [Laparoscopic splenectomy. The "hanging spleen technique" in a series of nineteen
      cases].
AB  - We have used an new patient position for laparoscopic splenectomy: the patient is
      placed in the right lateral supine position on a "bean bag" positioning apparatus
      and the left arm is elevated. The operator stands to the patient's right, the
      first assistant is on the patient's right and the second is on the patient's
      left. This position provides very good exposure of the spleen, which hangs from
      the diaphragm by the peritoneal attachments and the inferior pole splenic
      vessels, short gastric vessels and splenic hilus vessels can be released
      successively. We have now performed 19 splenectomies using the "Hanging Spleen
      Technique" with three conversions to open surgery. Splenectomy was always
      possible with the use of a plastic bag through the 12 mm trocar hole in 12 cases
      and through this enlarged hole in 2 cases. The mean post-operative stay was 4.3
      days and the mean time to return to work was 19 days. Laparoscopic splenectomy is
      a feasible and safe procedure with this patient position. Obesity and
      splenomegaly are no longer absolute contra-indications.

PMID- 8526437
TI  - [Splenectomy under celioscopy].
AB  - Laparoscopic splenectomy has been extensively developed since its first
      description by Delaitre in 1991. From May 1993 to July 1994, 12 patients
      underwent laparoscopic splenectomy in the "service de Chirurgie C" of the "CHU de
      Nancy". Six of them were successful. 6 women with a mean age of 27.7 years. The
      mean operating time was 2 h 30 min. For all cases, the indication was idiopathic
      thrombocytopenic purpura. No mortality and no morbidity was reported. One patient
      needed a blood transfusion. The postoperative stay ranged from 3 to 7 days.
      Splenectomy appears to be another procedure that may be successfully performed
      under laparoscopic guidance with satisfactory conditions of safety. The outcome
      evaluation should be continued in order to accurately define the real advantages
      and risks of this new technique.

PMID- 8526438
TI  - [Place of celio-video-surgery in splenectomy for hematologic diseases].
AB  - In order to evaluate the place of the laparoscopic approach in splenectomy for
      haematological disease, the authors prospectively studied a series of 25
      consecutive patients requiring splenectomy. There were 11 cases of
      thrombocytopenic purpura, 9 lymphomas, 2 cases of herediary spherocytosis, 1
      Felty syndrome, 1 idiopathic myelofibrosis and 1 Hodgkin disease. Twelve patients
      (48%) underwent an immediate conventional procedure for huge splenomegaly (10),
      obesity (1), unavailability of video-equipment. Thirteen patients (52%) underwent
      a laparoscopic approach. Five of these operations were converted into a
      conventional approach for various reasons. In the other 8 patients, the spleen
      was completely released laparoscopically. In two of these 8 patients, the spleen
      was removed via a sub-pubic Pfannenstiel incision due toits volume. The last 6
      spleens (24%) were removed in a plastic bag, corresponding to 5 cases of one
      thrombocytopenic purpura and one Hodgkin disease. None of these patients were
      obese. These results suggest that the laparoscopic approach is indicated in case
      of moderate splenemegaly in non-obese patients.

PMID- 8526439
TI  - [Laparoscopic splenectomy revisited].
AB  - We present a new technique for laparoscopic splenectomy which allows manual
      control of endoscopic dissection. After induction of pneumoperitoneum and
      insertion of an endoscope to check the absence of any contraindications, an
      incision is made for insertion of the hand and forearm. An airtight system
      allowing insertion of the hand while maintaining the pneumoperitoneum is fixed
      around the incision. A second port is inserted in the left flank. The procedure
      is then performed with laparoscopic instruments while the left hand allows for
      spleen mobilisation and easier exposure of the structures to be dissected and
      divided. Eight patients with a mean age of 51.3 years have been operated on for
      Idiopathic Thrombocytopenia. The average duration of the procedure was 90 min (80
      130 min). No postoperative complication occurred. The mean duration of stay was
      3.8 days (3-7 days). These results of this technique are encouraging. The
      procedure is quicker and safer than an exclusive laparoscopic approach. The
      incision allows removal of the intact spleen. Other applications of this system
      can be envisaged.

PMID- 8526440
TI  - [A hematologist's point of view].

PMID- 8526441
TI  - [Antibiotic prophylaxis in biliary surgery].
AB  - Prophylactic antibiotics in gallbladder surgery is designed to reduce the
      incidence of postoperative wound infections. Bacteria isolated from the biliary
      tract are generally the same as those found in the pus of wounds. Prospective and
      placebo-controlled trials have shown the efficacy of prophylactic antibiotics in
      high-risk patients presenting one or more of the following criteria: age over 70
      years, recent episode of acute chollecystitis, emergency cholecystectomy,
      presence of common duct stones, jaundice or diabetes mellitus in patients with no
      risk factors for gallbladder surgery, prophylactic antibiotics may not be
      essential. The efficacy of antibiotics in the prevention of wound infections has
      been demonstrated with first, second and third generation cephalosporins,
      ampicillin associated with clavulanate, ureido-penicillins, aminoglycosides,
      sulfonamides and quinolones. A single injection of antibiotic given one hour
      before incision is as effective as multiple-dose regimens. Currently, the choice
      of antibiotic should be mainly based on its cost. There is no evidence at the
      present time for systematic prophylactic antibiotics in laparoscopic surgery.
      Endoscopic procedures of the biliary tract do not require prophylactic
      antibiotics when obstruction has not been demonstrated.

PMID- 8526442
TI  - [Screening of multiple endocrine neoplasias type 1. Reflexions of the Study Group
      on Multiple Endocrine Neoplasias type 1].
AB  - The "Groupe d'Etude des Neoplasies Endocriniennes Multiples de type 1 (GENEM 1)"
      is a French group involved in a comprehensive multicentre study of Multiple
      Endocrine Neoplasia type 1 syndrome (NEM 1). The objectives of this group are to
      define diagnostic and therapeutic protocols and to carry out genetic research on
      NEM1. The first aim of physicians is to recognize the syndrome and to determine
      the appropriate screening especially into two circumstances: 1 degree In case of
      isolated and sporadic glandular disease -i-e-parathyroid glands, endocrine
      pancreas, antehypophysis, adrenal glands and neuroendocrine tumors? 2 degrees In
      case of very high probability of NEM 1 syndrome? This paper answers these two
      questions, based on the analysis of the first 150 cases collected by the GENEM 1.

PMID- 8526443
TI  - [Results of the celioscopic treatment of gastroesophageal reflux according to
      Nissen-Rossetti. Apropos of 94 cases].
AB  - From January 1992 to July 1993, 94 patients with symptomatic gastroesophageal
      reflux and/or hiatal hernia underwent laparoscopic Nissen-Rossetti
      fundoplication. The median follow-up was 4.5 months. There was no conversion to
      open surgery and no postoperative mortality. Laparoscopic reoperation was
      necessary in 2 patients haemorrhage and there were 2 cases of food impaction. 6
      patients developed a chest postoperative infection. 6 cases of dysphagia
      extending beyond 2 months were observed. In 3 of these cases, endoscopic
      dilatation provided effective treatment of dysphagia, and in 3 others, a further
      laparoscopic operation achieved cure. We observed 2 relapses of hiatal hernia,
      one of which was a voluminous recurrent paraesophageal hernia, and the other was
      a patient with slipped-Nissen. 84% of patients were satisfied with the surgical
      result. Laparoscopic fundoplication is an effective the treatment for
      gastroesophageal reflux.

PMID- 8526444
TI  - [Place of celioscopy in the diagnosis of invasiveness of digestive cancers].
AB  - The adequate treatment of gastrointestinal tract carcinoma requires accurate
      preoperative staging. Laparoscopy has been advocated for this purpose. We
      reviewed the data of 12 patients and the literature to compare the results of
      laparoscopic staging to those of conventional imaging (ultrasonography-CT scan).
      Laparoscopy was more sensitive in the diagnosis of peritoneal and lives
      metastases. It was inadequate for the diagnosis of lymph node metastases.
      Laparoscopy was especially useful in patients with esophagus, stomach, pancreas
      and liver cancers. Laparoscopic ultrasonography improved the staging of
      pancreatic carcinoma and the diagnosis of liver metastases.

PMID- 8526445
TI  - [Fundamental problems of xenograft].

PMID- 8526446
TI  - Pelvic pouch-anal anastomoses: pros and cons about omission of mucosectomy and
      loop ileostomy. A study of 60 patients.
AB  - Pelvic pouches were constructed in 60 consecutive patients from 1987 to 1991. The
      first 30 patients underwent mucosectomy and construction of handsewn reservoirs,
      and ileoanal anastomoses protected by loop ileostomy (group A). In the following
      12 patients (group B1) J pouches and ileoanal anastomoses were constructed by
      total stapling technique without mucosectomy, with a loop ileostomy. In the last
      18 patients the loop ileostomy was omitted (group B2). A comparison between group
      A and B and between group B1 and B2 was made concerning anaesthesia time,
      hospital stay, blood transfusions, postoperative complications and pouch function
      at 2 and 12 months. It was found that the stapling technique (group B) reduced
      anaesthesia time considerably and reduced the need of blood transfusions.
      Postoperatively thromboembolic episodes and signs of adrenal insufficiency were
      seen only in the handsewn group, while postoperative febrile conditions were more
      common in the stapled groups. Ileo-anal dehiscence occurred in two patients
      without loop ileostomy. Treatment by establishment of a loop ileostomy, local
      irrigation and administration of antibiotics were successful, the anastomoses
      healed within 2 weeks and there was no further complications before or after loop
      closure. Omitting the loop ileostomy saved the patient a further operation and
      reduces hospital stay and sick leave. After two months of pouch function,
      patients with handsewn pouches had a lower number of bowel movements (5.5/24 h
      and 0.8 during the night) than patients with stapled pouches (8.0/24 h and 1.9
      during the night). At 12 months, however, the difference between the groups of
      patients had diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526447
TI  - [Immediate vaginal reconstruction with a musculocutaneous flap from the gracilis
      muscle after extended abdomino-perineal resection].
AB  - Reconstruction of a functional vagina after radical abdomino-perineal resection
      is a difficult surgical problem. The use of the gracilis myocutaneous flap
      provides a satisfactory solution. This article describes the surgical procedure
      of immediate vaginal reconstruction using the gracilis myocutaneous flap.
      Unfortunately, this technique is still not widely used by surgical teams.
      Nevertheless, it is a useful flap because of its low morbidity and the satisfying
      result of the functional neovaginal cavity.

PMID- 8526448
TI  - [Preliminary evaluation of composite materials for the repair of incisional
      hernias].
AB  - Recent investigations have shown that direct exposure of the intestines to
      currently available absorbable and nonabsorbable biomaterials can result in their
      adhesion to the bowel. This can then lead to bowel obstruction or migration of
      the mesh into the intestinal lumen and formation of intestinal fistula. It has
      been suggested by some authors that an absorbable covering of the peritoneal side
      of a nonabsorbable mesh would prevent adhesions and biomaterial related
      intestinal fistula formation. However, the effectiveness of such a combination
      has not been substantiated by recent experimental and clinical studies. This
      preliminary report examines the feasibility of combining porous and non-porous
      biomaterials for the creation of a composite that would incorporate with the
      abdominal wall without adhering to the intestines.

PMID- 8526449
TI  - [Results of a controlled trial comparing 3 suture threads at slow resorption for
      the closure of supra-umbilical midline laparotomies].
AB  - A randomized prospective trial was carried out between September 1987 and
      February 1989 to compare 3 different absorbable sutures (polyglactine 910,
      polydioxanone I, polydioxanone II) for closure of the abdominal wall after upper
      midline laparotomy for elective operations. The technique used to close the
      fascia was always a continuous suture. The criteria used to assess the results
      were the development of wound infection and wound dehiscence in the early
      postoperative period, and the development of suture sinuses and incisional hernia
      1 year after operation. The early postoperative results in 235 patients revealed
      no wound infection and no -wound dehiscence. Suture sinuses developed in 4
      patients (2%) 2 months after operation, but resolved spontaneously. We reviewed
      203 patients after one year. The total number of incisional hernias detected 1
      year postoperatively was 22 cases (11%), (polyglactine 910, 14.2%; polydioxanone
      I, 11.2%; polydioxanone II, 8.4%). The difference between the 3 groups was not
      statistically significant. The results of the trial indicate that absorbable
      sutures have a very low incidence of suture sinuses, and that polydioxanone II
      seems to be a good choice for closing laparotomies.

PMID- 8526450
TI  - [Intrathoracic gastric volvulus complicating Nissen's laparoscopic operation.
      Apropos of a case].

PMID- 8526451
TI  - [Hepatic angiosarcoma with pulmonary metastases].

PMID- 8526452
TI  - [Rectal stenosis following prolonged use of suppositories of acetylsalicylic acid
      and paracetamol. Correction by perineal approach].

PMID- 8526453
TI  - [Recommendations concerning the relation between anesthetists, surgeons and other
      health care professionals].

PMID- 8526454
TI  - Selective neurodegeneration in Huntington's disease.

PMID- 8526455
TI  - Writer's cramp: a disorder of motor subroutine?

PMID- 8526456
TI  - Neural apoptosis.
AB  - Apoptosis is a mode of cell death in which the cell plays an active role in its
      own demise. The study of neural apoptosis, the identification of genes
      controlling apoptosis, and the examination of the mechanisms by which these genes
      achieve their effects have assumed increasing importance over the past few years.
      This is because (1) neural apoptosis occurs not only in development, but also in
      pathophysiological states such as stroke, glutamate toxicity, and beta-amyloid
      peptide toxicity; (2) genes that control apoptotic cell death, such as bcl-2,
      p35, p53, and p75NTR, also modulate necrotic neural death in some cases; (3) the
      emerging mechanisms by which these genes control apoptosis may be relevant for
      understanding neurodegenerative processes, and for the design of therapeutic
      agents; and (4) the findings that the cell plays an active role in its own
      demise, and that specific gene products are involved, suggest that therapeutic
      intervention may be feasible.

PMID- 8526457
TI  - Preferential loss of preproenkephalin versus preprotachykinin neurons from the
      striatum of Huntington's disease patients.
AB  - Preferential loss of basal ganglia neurons and terminals occurs in Huntington's
      disease (HD). Terminals of preproenkephalin medium-size spiny neurons are more
      vulnerable than terminals of preprotachykinin neurons, but the peptidergic
      neurons of origin have not yet been shown to die preferentially. We sought to
      determine, in the striatum, whether preproenkephalin neurons were lost to a
      greater extent than preprotachykinin neurons and to determine whether there were
      decreases in specific messenger RNA (mRNA) levels of preproenkephalin,
      preprotachykinin, and calbindin D28k. We found a grade-related decrease in the
      number of preprotachykinin- and calbindin D28k-labeled neurons per measuring
      field in the caudate nucleus of patients with HD. Three measures of the neuronal
      level of preprotachykinin mRNA were all significantly reduced (6-65% of control
      values) in HD caudate nucleus. No decline in calbindin D28k mRNA levels per
      neuron were found in HD striata compared to control striata. We found a greater
      loss of preproenkephalin neurons per field than preprotachyknin neurons per field
      in the caudate nucleus of HD brains compared to control brains. Preprotachykinin
      neurons are lost in HD in a grade-related manner and surviving preprotachykinin
      neurons are impaired in function. However, preproenkephalin neurons are lost to a
      greater extent than preprotachykinin neurons, which may explain preferential
      changes found in projection regions of the striatum. Declines in neuropeptide
      mRNA may be specific in HD, since calbindin D28k mRNA levels were unchanged.
      Alterations in the levels of expression of preproenkephalin and preprotachykinin
      mRNA may be direct or indirect effects of the HD mutation.

PMID- 8526458
TI  - Movement-related cortical potentials in writer's cramp.
AB  - Movement-related cortical potentials in response to simple, self-paced, brisk
      index finger abduction movements were recorded in patients with simple and
      complex writer's cramp and compared with those of age-matched control subjects.
      Analysis of the movement-related cortical potential waveforms showed that the
      Bereitschaftspotential, the peak of the negative slope, and the frontal peak of
      the motor potential did not differ in the two groups, except for the average
      amplitude of the early part of the negative-slope peak, which was decreased in
      the patient group during the interval of 300 to 200 msec prior to
      electromyographic onset. This finding was restricted to the electrodes overlying
      the contralateral and midline central electrodes. Movement-related cortical
      potentials from patients and control subjects could be equally accounted for by a
      four-dipole source model with sources located in the contralateral and
      ipsilateral sensorimotor regions and the supplementary motor area. There was a
      trend for a reduction in the strength of the sensorimotor sources active during
      the premotor period in the patient group, but the difference did not reach a
      significant level for any individual source. No differences were found between
      the movement-related cortical potentials elicited by movements of the affected
      and unaffected hand, or between those of patients with simple or complex hand
      cramps. This result suggests a deficiency of contralateral motor cortex
      activation just prior to the initiation of voluntary movements in patients with
      focal dystonia.

PMID- 8526459
TI  - Effect of intensive diabetes treatment on nerve conduction in the Diabetes
      Control and Complications Trial.
AB  - The Diabetes Control and Complications Trial demonstrated that intensive diabetes
      therapy effectively delays the onset of clinically apparent neuropathy in
      patients with insulin-dependent diabetes mellitus. A total of 1,441 patients with
      insulin-dependent diabetes mellitus were randomly assigned to receive intensive
      treatment or conventional treatment. Of these, 1,290 were randomized at least 4
      1/2 years or more prior to study termination. Nerve conduction studies were
      performed at baseline and repeated after approximately 5 years for 1,243 of these
      patients, 96% of the eligible population. After 5 years of treatment, significant
      nerve conduction differences were observed between the intensive and conventional
      treatment groups, all favoring better performance (faster sensory and motor
      conduction velocities and shorter F-wave latencies) in the intensive treatment
      group. Moreover, while performance generally deteriorated among the
      conventionally treated patients, most attributes remained stable or showed modest
      improvement in the intensively treated group. Treatment group differences were
      consistent across strata defined by duration of diabetes and the presence of
      neuropathy at baseline. A nonparametric multivariate test of all ten nerve
      conduction measures established a strong effect in favor of intensive treatment.
      These data confirm that the electrophysiological abnormalities associated with
      diabetic neuropathy are delayed or prevented by intensive diabetes treatment.

PMID- 8526460
TI  - Cerebellar outflow lesions: a comparison of movement deficits resulting from
      lesions at the levels of the cerebellum and thalamus.
AB  - Previous work has shown that lesions in the lateral cerebellum involving the
      dentate nucleus impair both reaching and pinching movements in humans and
      monkeys. This study addressed the question of whether disruption of the
      cerebellar-thalamo-cortical pathway at the level of the thalamus would produce
      behavioral deficits similar to those seen after dentate damage. We compared the
      performance of both reaching and pinching movements in patients with lateral
      cerebellar lesions and in patients with discrete lesions of the ventrolateral
      thalamus. The patients with thalamic lesions had minimal or no sensory loss and
      no corticospinal signs, suggesting that the abnormal movements were due to
      disruption of the cerebellar projection to the thalamus. We found that lesions of
      the ventrolateral thalamus resulted in impaired pinching movements, but
      remarkably normal reaching movements with the exception of a slight tremor. This
      is in contrast to the profound pinching and reaching impairments of patients with
      lateral cerebellar lesions involving the dentate nucleus. Implications about the
      functional organization of cerebellar output are discussed.

PMID- 8526461
TI  - Experimental status epilepticus alters gamma-aminobutyric acid type A receptor
      function in CA1 pyramidal neurons.
AB  - There is a reduction of gamma-aminobutyric acid (GABA)-mediated inhibition of the
      CA1 pyramidal region of the hippocampus during status epilepticus (SE). The
      cellular basis of this loss of GABA-mediated inhibition is not known. This study
      tested the possibility that GABA type A (GABAA) receptor function in CA1
      pyramidal neurons was reduced or blocked during SE, at least in part by
      postsynaptic cellular mechanisms. GABAA receptor currents (IGABA) were studied by
      whole-cell patch-clamp techniques in CA1 pyramidal neurons acutely dissociated
      from rats undergoing lithium/pilocarpine-induced limbic status epilepticus (SE
      neurons) and from naive rats (naive neurons). SE neurons had more depolarized
      resting membrane potential (-17.3 mV) compared with naive neurons (-56 mV). IGABA
      was absent in 47% of SE neurons and reduced in 55% of the remainder, compared
      with naive neurons. The reduction in IGABA in SE neurons resulted from a
      combination of factors, including reduced potency and reduced efficacy of GABA in
      activating chloride channels, and diminished driving force for the GABA-induced
      chloride currents once activated. These postsynaptic cellular mechanisms resulted
      in a net reduction or loss in GABA-mediated inhibition and may explain previous
      in vivo findings reporting a loss of inhibition in hippocampus during limbic SE.

PMID- 8526462
TI  - Chemical pathology of acute demyelinating lesions and its correlation with
      disability.
AB  - We report the chemical pathological changes on magnetic resonance spectroscopic
      images of 4 patients, each of whom had a single large demyelinating plaque. The
      patients were followed from soon after the onset of the symptoms for a minimum of
      7 months to a maximum of 3 1/2 years. We observed increases in the relative
      resonance intensities of choline-containing compounds, lactate, and myo-inositol
      inside the lesion acutely. Decreases in relative resonance intensities of N
      acetylaspartate and creatine were seen both in and around the magnetic resonance
      imaging-detected lesions. In all patients neurological deficits improved and
      creatine, lactate, and myo-inositol resonance intensities normalized during the
      follow-up. Choline compounds recovered more slowly and were still abnormally high
      in 1 patient after 7 months. Partial recovery of the N-acetylaspartate resonance
      was seen for all patients. Evaluation of the relationships between indices of
      cerebral chemical pathology, brain lesion volumes, and functional disability
      showed highly significant negative correlations between N-acetylaspartate
      resonance intensities and both brain lesion volumes (r = -0.80, p < 0.0001) and
      clinical disability (r = -0.73, p < 0.0001). As N-acetylaspartate is localized
      solely in neurons in the adult central nervous system, our results suggest that
      neuronal dysfunction may be a proximate mechanism of disability even in
      inflammatory disorders primarily affecting myelin and oligodendroglial cells.

PMID- 8526463
TI  - The role of reading activity on the modulation of motor cortical outputs to the
      reading hand in Braille readers.
AB  - We studied the cortical motor output maps of the first dorsal interosseous (FDI)
      of both hands and the abductor digiti minimi of the reading hand in 6 blind
      proficient Braille readers. The maps were generated using transcranial magnetic
      stimulation. We compared the maps obtained on a day in which they worked as
      Braille proofreaders (reading Braille for approximately 6 hours) with the maps
      obtained on a day they took off from work. On the work day, the maps for the FDI
      of the reading hand were significantly larger after the working shift than in the
      morning after having been off work for 2 days. These changes were not seen for
      the same muscle on the day off work or on any of the 2 days in the other two
      muscles studied. These results illustrate the rapid modulation in motor cortical
      outputs in relation to preceding activity and emphasize the importance of precise
      timing in studies of the neurophysiological correlates of skill acquisition.

PMID- 8526464
TI  - Neuromuscular effects of Papuan Taipan snake venom.
AB  - Snakebite is a cause of significant morbidity in Central Province, Papua New
      Guinea. Three adult patients with clinical evidence of neurotoxicity following
      envenomation by the Papuan taipan had serial neurophysiological examinations over
      the course of their subsequent hospitalization. All required artificial
      ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP)
      amplitudes declined over the first 2 to 4 days after envenoming and then
      gradually increased in parallel with clinical recovery. Repetitive stimulation
      studies revealed a distinctive pattern of abnormality. Activation resulted in
      brief potentiation of the CMAP followed by significantly greater decrement than
      observed at rest. This effect lasted up to 30 minutes and was not altered after
      intravenous edrophonium. Single-fiber electromyographic recordings during the
      recovery phase of the illness were abnormal with marked blocking and increased
      jitter. All patients were able to return home.

PMID- 8526465
TI  - Early copper therapy in classic Menkes disease patients with a novel splicing
      mutation.
AB  - To correlate genotype with response to early copper histidine therapy in Menkes
      disease, an X-linked disorder of copper transport, we performed mutational
      analysis in 2 related males who began treatment at the age of 10 days and
      prenatally at 32 weeks' gestation, respectively. A G to T transversion at the -1
      exonic position of a splice donor site was identified, predicting a glutamine to
      histidine substitution at codon 724 of the Menkes copper-transporting ATPase
      gene. The Q724H mutation disrupts proper splicing and generates five mutant
      transcripts that skip from one to four exons. None of these transcripts is
      predicted to encode a functional copper transport protein. Copper histidine
      treatment normalized circulating copper and ceruloplasmin levels but did not
      improve the baseline deficiency of dopamine-beta-hydroxylase, a copper-dependent
      enzyme. At the age of 36 months, the first patient was living and had
      neurodevelopmental abilities ranging from 10 to 15 months. The second patient
      also showed delayed neurodevelopment and died of pulmonary complications at the
      age of 5 1/2 months. We conclude that early copper histidine therapy does not
      normalize neurological outcome in patients with the Q724H splicing mutation, and
      suggest that preservation of some residual Menkes ATPase activity may be a
      general prerequisite for significant clinical efficacy from such treatment.

PMID- 8526466
TI  - Familial subarachnoid hemorrhage: distinctive features and patterns of
      inheritance.
AB  - To delineate the distinctive features of familial subarachnoid hemorrhage, we
      compared gender and age at the time of subarachnoid hemorrhage, as well as site
      and number of aneurysms, in patients with familial subarachnoid hemorrhage (at
      least 1 first-degree relative with subarachnoid hemorrhage) and patients with
      sporadic subarachnoid hemorrhage (no subarachnoid hemorrhage in first- or second
      degree relatives), in a prospective, hospital-based series of patients. In
      addition we studied the pattern of inheritance in 17 families with familial
      subarachnoid hemorrhage. Mean age at the time of hemorrhage in patients with the
      familial form was 6.8 years lower than that in those with the sporadic form, and
      middle cerebral artery aneurysms occurred more often in patients with familial
      disease. Sex distribution and number of aneurysms were similar in the two groups.
      Inheritance was compatible with autosomal dominant transmission in some families,
      and with autosomal recessive or multifactorial transmission in others. In our 5
      families as well as in all 18 previously reported families with two affected
      generations, the age at the time of subarachnoid hemorrhage was invariably lower
      in later generations, which is suggestive of anticipation. We conclude that
      familial subarachnoid hemorrhage is a separate entity with occurrence at a young
      age, predilection for aneurysms of the middle cerebral artery, and variable modes
      of inheritance, including autosomal dominant inheritance with possible
      anticipation.

PMID- 8526467
TI  - Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats.
AB  - We tested the neuroprotective potential of neutrophil inhibitory factor (rNIF), a
      novel 41-kd recombinant glycoprotein derived from a hookworm, in a model of focal
      cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with
      rNIF and vehicle. Middle cerebral artery occlusion (MCAO) for 2 hours was induced
      by insertion of an intraluminal suture. Infusion of the drug was initiated at the
      onset of reperfusion. Infarct volume was determined 48 hours after reperfusion.
      Neutrophils were measured within the ischemic tissue by myeloperoxidase (MPO)
      staining. Treatment with rNIF resulted in a 48% reduction in cerebral infarction
      compared with control animals (p < 0.01). Neutrophil accumulation in the ischemic
      brains of rNIF-treated rats was reduced significantly (p < 0.01) compared with
      control animals. The number of neutrophils within the infarcted tissue correlated
      positively with the size of the area of infarction (p < 0.001, r = 0.6) within
      representative cerebral coronal sections. We demonstrated a significant
      neuroprotective effect of rNIF with continuous treatment for 48 hours following 2
      hours of MCAO. The neuroprotective effect was correlated with a reduced number of
      neutrophils within the ischemic tissue. These results demonstrate potential
      therapeutic properties of rNIF in the management of stroke.

PMID- 8526468
TI  - Acute optic neuritis: myelin basic protein and proteolipid protein antibodies,
      affinity, and the HLA system.
AB  - Anti-myelin basic protein, anti-proteolipid protein, and anti-myelin basic
      protein peptide (amino acid residues 1-20, 63-88, and 89-101) antibody-secreting
      cells were studied in 20 patients with idiopathic optic neuritis, 20 with optic
      neuritis as part of multiple sclerosis, and 20 neurological control subjects.
      Antibody-secreting cells were enumerated with an immunospot assay; the relative
      binding affinity of the antibodies was estimated by elution with thiocyanate.
      Patients with optic neuritis had more anti-myelin basic protein and anti
      proteolipid protein antibodies than did control subjects (both p < 0.05); there
      was no difference between idiopathic optic neuritis and optic neuritis as a
      symptom of multiple sclerosis. Presence of the multiple sclerosis-associated
      DRB1*1501 gene was not associated with preferential synthesis of high-affinity
      antibodies reactive with a single myelin basic protein peptide or with
      preferential synthesis of either anti-myelin basic protein or anti-proteolipid
      protein antibodies. The results demonstrate a potential for intrathecal synthesis
      of both anti-myelin basic protein and anti-proteolipid protein antibodies of high
      apparent affinity in patients with optic neuritis.

PMID- 8526469
TI  - Intractable partial epilepsy following low-dose scalp irradiation in infancy.
AB  - We report the development of intractable epilepsy in 3 patients treated with
      irradiation to "strawberry" scalp nevi in infancy. Low-dose radiation was used
      (12 and 13 Gy in 2 of the patients). The clinical evolution suggested a
      recognizable and distinctive postradiation syndrome. There was concordance
      between the site of radiation as shown by localized alopecia, the clinical
      features of the partial seizures, and electrographic abnormalities. The clinical
      picture was unlike delayed cerebral radiation necrosis of adulthood, which is not
      thought to occur at doses below 50 Gy, in 2-Gy fractions. Neurological deficits
      were not progressive and in 2 patients there was no evidence of parenchymal
      injury on cranial magnetic resonance imaging scanning. These differences suggest
      pathogenetic differences to cerebral radiation injury of adulthood, probably
      relating to the interaction between nervous system development, individual
      susceptibility, and the low doses of radiation employed.

PMID- 8526470
TI  - Striatal dopaminergic denervation in pallidopyramidal disease demonstrated by
      positron emission tomography.
AB  - Pallidopyramidal disease is a rare disease of young patients in which they
      manifest a parkinsonian syndrome and pyramidal signs. Pallidopyramidal disease
      has been attributed to a degeneration of the pallidum and the pyramidal tract,
      although only 1 patient has been studied postmortem. In the present report,
      [18F]fluorodopa positron emission tomography in 2 patients showed a marked
      dopaminergic denervation of the striatum, suggesting that this disease
      corresponds more to a nigropallidopyramidal dysfunction.

PMID- 8526471
TI  - Apolipoprotein E epsilon 4 in inclusion body myositis.
AB  - The genetic predisposition to inclusion body myositis (IBM) is probably
      multifactorial. The deposition of the beta-amyloid protein is a characteristic
      histological feature of both IBM and Alzheimer's disease (AD). The epsilon 4
      allele of apolipoprotein E (APO E) has been strongly associated with familial and
      late-onset AD. We therefore compared the APO E allele frequencies in a group of
      14 patients with IBM with those in a group of patients with other inflammatory
      muscle diseases and in the general population. The frequency of the epsilon 4
      allele in IBM was increased (0.29) compared with that in patients with other
      inflammatory muscle diseases (0.15) and the general population (0.13) (p < 0.05).
      These data suggest that APO E genotype may be one of the factors involved in
      determining the predisposition to the development of IBM.

PMID- 8526472
TI  - Cerebrovascular complications in Ehlers-Danlos syndrome type IV.
AB  - Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant disorder that
      results from mutations in the COL3A1 gene, which encodes chains of type III
      procollagen. Individuals with this disorder are predisposed to rupture of
      arteries, the bowel, and the gravid uterus. To assess the frequency of central
      nervous system complications, we reviewed clinical data concerning 202
      individuals with EDS type IV from 121 families in which the diagnosis was
      confirmed by biochemical or molecular studies. We identified 19 individuals with
      cerebrovascular complications, which included intracranial aneurysms with
      secondary hemorrhage, spontaneous carotid-cavernous sinus fistula, and cercical
      artery dissection. The mean age at presentation with these events was 28.3 years
      (range, 17-48 years). Although uncommon, EDS type IV is an important potential
      cause of stroke in young people. The disorder is readily identifiable clinically
      and the diagnosis has important implications for acute and long-term management
      and, potentially, for other family members. Because conventional angiography may
      exacerbate severe complications, noninvasive procedures such as Doppler and
      magnetic resonance angiography are the investigations of choice. Anticoagulation
      therapy may result in increased bruising or bleeding and should be used with
      caution.

PMID- 8526473
TI  - Locomotor training in paraplegic patients.

PMID- 8526474
TI  - Olivopontocerebellar atrophy.

PMID- 8526475
TI  - Apolipoprotein E genotyping in the diagnosis of Alzheimer's disease: a cautionary
      view.

PMID- 8526476
TI  - Apolipoprotein E genotyping in the diagnosis of Alzheimer's disease.

PMID- 8526477
TI  - Phylogenetic analysis of ten black yeast species using nuclear small subunit rRNA
      gene sequences.
AB  - The nuclear small subunit rRNA genes of authentic strains of the black yeasts
      Exophiala dermatitidis, Wangiella dermatitidis, Sarcinomyces phaemuriformis,
      Capronia mansonii, Nadsoniella nigra var. hesuelica, Phaeoannellomyces elegans,
      Phaeococcomyces exophialae, Exophiala jeanselmei var. jeanselmei and E.
      castellanii were amplified by PCR and directly sequenced. A putative secondary
      structure of the nuclear small subunit rRNA of Exophiala dermatitidis was
      predicted from the sequence data. Alignment with corresponding sequences from
      Neurospora crassa and Aureobasidium pullulans was performed and a phylogenetic
      tree was constructed using the neighbor-joining method. The obtained topology of
      the tree was confirmed by bootstrap analysis. Based upon this analysis all fungi
      studied formed a well-supported monophyletic group clustering as a sister group
      to one group of the Plectomycetes (Trichocomaceae and Onygenales). The analysis
      confirmed the close relationship postulated between Exophiala dermatitidis,
      Wangiella dermatitidis and Sarcinomyces phaeomuriformis. This monophyletic clade
      also contains the telemorph species Capronia mansonii thus confirming the concept
      of a teleomorph connection of the genus Exophiala to a member of the
      herpotrichiellaceae. However, Exophiala castellanii did not belong to this clade.
      Therefore, this species is not the anamorph of Capronia mansonii as it was
      postulated.

PMID- 8526478
TI  - Fruiting studies in species of Capronia (Herpotrichiellaceae).
AB  - A recently described protocol for the in vitro production of ascomata was
      employed to determine the sexual incompatibility systems of five species of
      Capronia. The formation of mature ascomata in isolates derived from single
      ascospores demonstrated that C. epimyces, C. mansonii, and C. munkii n. sp. are
      homothallic. In contrast, fertile ascomata were observed only in mass-ascospore
      isolates and pairwise crosses between specific single-ascospore isolates in C.
      dactylotricha n. sp. and C. moravica. The Exophiala anamorphs of C. dactylotricha
      and C. munkii are described and a Phialophora-like synanamorph is reported for
      the former species. Germinating ascospores of C. munkii formed conidiogenous
      cells directly, while the ascospores of the remaining species germinated to
      produce germ tubes and hyphae. The application of the terms 'microcyclic
      conidiation' to secondary conidium production and 'sclerotial body' and 'stroma'
      to the multicellular structures produced by species of Capronia and Exophiala are
      discussed.

PMID- 8526479
TI  - PCR-ribotyping of type isolates of currently accepted Exophiala and
      Phaeococcomyces species.
AB  - Portion of the ribosomal repeat of the type strains of the genera Exophiala and
      Phaeococcomyces were subjected to RFLP analysis. The amplicon length of the small
      subunit rRNA, the fragment NS1-NS24, was found to vary between 1800 to 3200
      nucleotides. In contrast, the length of the fragment ITS1-ITS4 comprising the
      internal transcribed spacers (ITS1 and ITS2) was found to be constant at 600
      nucleotides. Analysis of restriction profiles confirmed the synonymy of Exophiala
      dermatitidis and Mycotorula schawaii. Torula bergeri and Sporotrichum gougerotii
      were found to be identical to Phaeoannellomyces elegans, but different from their
      alleged synonym E. castellanii. A phenogram is presented.

PMID- 8526480
TI  - Nutritional physiology of type isolates of currently accepted species of
      Exophiala and Phaeococcomyces.
AB  - Nutritional physiological and tolerance tests were performed for all type strains
      of species currently classified in the black yeast genera Exophiala and
      Phaeococcomyces, including some additional type strains of taxa recently
      reidentified as Exophiala species. Most described Exophiala species can be
      distinguished by physiological characters. Exophiala jeanselmei with its
      varieties, and E. castellanii should all be retained as separate taxa. The pairs
      of strains Mycotorula schawii/Exophiala dermatitidis, Hormodendrum
      negronii/Exophiala jeanselmei var. lecaniicorni and Sporotrichum
      gougerotii/Torulabergeri were found to be conspecific. Phenetic analyses of
      physiological data support the identity of Phaeococcomyces exophialae as a yeast
      like synanamorph of Exophiala spinifera. The taxonomic positions of the genera
      Nadsoniella, Phaeoannellomyces and Wangiella are discussed. The genera Exophiala
      and Phaeococcomyces are unrelated.

PMID- 8526481
TI  - Conidial surface ultrastructure of human-pathogenic and saprobic Cladosporium
      species.
AB  - Freeze-fracturing of outer wall layers of Cladosporium conidia revealed two types
      of ultrastructure, coinciding with taxonomic characteristics. The outer conidial
      layers were essentially smooth in the human pathogenic species, C. bantianum, C.
      carrionii, and C. trichoides. In contrast, mosaic arrays of rodlets on conidia
      were observed with freeze-fracturing in the saprobic species, C. cladosporioides,
      C. coralloides, C. herbarum, C. sphaerospermum, and C. variabile. Conidia of C.
      elatum were an exception among the saprobic species as they had smooth surfaces.
      The present study supports the suggestion that the human pathogenic Cladosporium
      species should be transferred to another genus.

PMID- 8526482
TI  - Intraspecific variability and exopolysaccharide production in Aureobasidium
      pullulans.
AB  - Forty seven strains of the black yeasts, Aureobasidium pullulans and Hormonema
      dematioides, and the type strain of Hormonema macrosporum were examined using PCR
      ribotyping and universally primed PCR with subsequent hybridization. Four groups
      (populations) were distinguished within A. pullulans with PCR-ribotyping, which
      largely coincided with UP-PCR/hybridization groups. The UP-PCR technique revealed
      a greater degree of heterogeneity between the groups studied. Five strains
      identified as Hormonena dematioides on the basis of physiological and
      morphological data formed a group recognizable with PCR-ribotyping and UP
      PCR/hybridization, which also included H. macrosporum. Aureobasidium pullulans is
      characterized by the absence of RsaI restriction sites in rDNA amplified with
      primers 5.8S-R and LR7, while Hormonema species possessed several bands after
      RsaI digestion. For analysis of distance between populations, PCR-ribotyping with
      AluI and MspI is sufficient. Strains of A. pullulans produce exopolysaccharides
      in liquid media with different nitrogen sources, while the strains of Hormonema
      synthesize minor amounts of polysaccharides in media with peptone. Populations of
      A. pullulans differ slightly from each other in their optimal, medium-dependent
      production of polysaccharides.

PMID- 8526483
TI  - Molecular characterization and identification of Saprolegnia by restriction
      analysis of genes coding for ribosomal RNA.
AB  - Restriction fragment length polymorphisms (RFLPs) in two regions of the ribosomal
      DNA (rDNA) repeat unit were examined in 33 strains representing 18 species of
      Saprolegnia. The Polymerase Chain Reaction (PCR) was used to separately amplify
      the 18S rDNA and the region spanning the two internal transcribed spacers (ITS)
      and the 5.8S ribosomal RNA gene. Amplified products were subjected to a battery
      of restriction endonucleases to generate various fingerprints. The internal
      transcribed spacer region exhibited more variability than the 18S rDNA and
      yielded distinctive profiles for most of the species examined. Most of the
      species showing 100% similarity for the 18S rDNA could be distinguished by 5.8S +
      ITS restriction polymorphisms except for S. hypogyna, S. delica, S. lapponica,
      and S. mixta. The rDNA data indicate that S. lapponica and S. lapponica and S.
      mixta are conspecific with S. ferax, whereas there is no support for the proposed
      synonymies of S. diclina with S. delica and of S. mixta with S. monoica. Results
      from cluster analysis of the two data sets were very consistent and tree
      topologies were the same, regardless of the clustering method used. A further
      examination of multiple strains in the S. diclina-S. parasitica complex showed
      that restriction profiles are conserved across different strains of S. parasitica
      originating from the U.K. and Japan. HhaI and BsaI restriction polymorphisms were
      observed in isolates from the U.S. and India. The endonuclease BstUI was
      diagnostic for S. parasitica, generating identical fingerprints for all stains
      regardless of host and geographic origin. Except for the atypical strain ATCC
      36144, restriction patterns were also largely conserved in S. diclina.
      Correlation of the rDNA data with morphological and ultrastructural features
      showed that S. diclina and S. parasitica are not conspecific. Restriction
      polymorphisms in PCR-amplified rDNA provide a molecular basis for the
      classification of Saprolegnia and will be useful for the identification of
      strains that fail to produce antheridia and oogonia.

PMID- 8526484
TI  - Species delimitation in the genus Lipomyces by nuclear genome comparison.
AB  - Species delimitation in Lipomyces was attempted by nuclear genome comparison in
      conjunction with the re-evaluation of 48 physiological characters of 65 strains.
      High intraspecific (> 75%) and low interspecific (< 28%) similarity values
      established that L. japonicus, L. lipofer and L. tetrasporus are genetically
      isolated, and also distinct from L. kononenkoae and L. starkeyi. Ambiguous
      similarity values were obtained with L. kononenkoae and L. starkeyi. Strains
      previously assigned to L. kononenkoae constitute two related clusters. While
      similarity values within each cluster range from 76-99%, representatives of the
      two clusters reassociate for only 47%. Since these clusters are differentiated by
      their ecologically relevant maximum growth temperature, L. kononenkoae is
      subdivided. Strains previously assigned to L. starkeyi resolve into four closely
      related clusters. While similarity values within each cluster range from 78-100%,
      representatives of the four clusters reassociate for only 59-69%. Since these
      four clusters are poorly differentiated, the subdivision of L. starkeyi does not
      appear possible without recourse to other criteria. Four unassigned strains
      constitute a further two clusters. Reassociation within these clusters is of the
      order of 91-100%, while reassociation between them occurs only at 59%.
      Reassociation of representatives of these clusters with those of the L.
      kononenkoae and L. starkeyi complexes is around 40% and 31%, respectively. These
      two clusters consequently appear to be intermediate between L. kononenkoae and L.
      starkeyi, and will, as such, have to be considered in any delimitation of these
      two species. A key to the taxa of Lipomyces and related genera of the
      Lipomycetaceae is given.

PMID- 8526485
TI  - Extracellular enzyme synthesis in a sporulation-deficient strain of Bacillus
      licheniformis.
AB  - A deletion of the spoIIAC gene of Bacillus licheniformis was prepared in vitro by
      using the splicing-by-overlap-extension technique. This gene was introduced into
      B. licheniformis on a temperature-sensitive plasmid, and following integration
      and excision from the chromosome, a precisely located deletion on the chromosomal
      gene was prepared. The mutated bacterium was totally asporogenous and formed
      abortively disporic cells characterized by asymmetric septa at the poles of the
      cells. Qualitative plate tests revealed that the bacterium synthesized normal
      levels of DNase, polygalacturonate lyase, protease, RNase, and xylanase, but the
      hydrolysis zones due to beta-1,3-glucanase and carboxymethyl cellulase activity
      were smaller in the mutant than in the parent strain. The synthesis of alkaline
      protease was the same in batch cultures of the mutant and the parent during
      prolonged incubation for 72 h, but the alpha-amylase yields were reduced by about
      30% by the mutation.

PMID- 8526486
TI  - Bioactivation of cysteine conjugates of 1-nitropyrene oxides by cysteine
      conjugate beta-lyase purified from Peptostreptococcus magnus.
AB  - To determine the role of cysteine conjugate beta-lyase (beta-lyase) in the
      metabolism of mutagenic nitropolycyclic aromatic hydrocarbons, we determined the
      effect of beta-lyase on the mutagenicities and DNA binding of cysteine conjugates
      of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10
      dihydro-1-nitropyrene (1-NP 9,10-oxide), which are detoxified metabolites of the
      mutagenic compound 1-nitropyrene. We purified beta-lyase from Peptostreptococcus
      magnus GAI0663, since P. magnus is one of the constituents of the intestinal
      microflora and exhibits high levels of degrading activity with cysteine
      conjugates of 1-nitropyrene oxides (1-NP oxide-Cys). The activity of purified
      beta-lyase was optimal at pH 7.5 to 8.0, was completely inhibited by
      aminooxyacetic acid and hydroxylamine, and was eliminated by heating the enzyme
      at 55 degrees C for 5 min. The molecular weight of beta-lyase was 150,000, as
      determined by fast protein liquid chromatography. S-Arylcysteine conjugates were
      good substrates for this enzyme. As determined by the Salmonella mutagenicity
      test, 5 ng of beta-lyase protein increased the mutagenicity of the cysteine
      conjugate of 1-NP 9,10-oxide (10 nmol per plate) 4.5-fold in Salmonella
      typhimurium TA98 and 4.1-fold in strain TA100. However, beta-lyase had little
      effect on the cysteine conjugate of 1-NP 4,5-oxide (10 nmol per plate). Both
      conjugates exhibited only low levels of mutagenicity with nitroreductase
      deficient strain TA98NR. In vitro binding of 1-NP oxide-Cys to calf thymus DNA
      was increased by adding purified beta-lyase or xanthine oxidase.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8526487
TI  - Recombination of a 3-chlorobenzoate catabolic plasmid from Alcaligenes eutrophus
      NH9 mediated by direct repeat elements.
AB  - Alcaligenes eutrophus NH9 was isolated from soil. This strain can utilize 3
      chlorobenzoate (3-CB) as a sole source of carbon and energy. Most of the 3-CB
      negative segregants had lost one of the plasmids present in the parent strain.
      The genes for catabolism of 3-CB were located within a 9.2-kb SacI fragment of
      this plasmid (pENH91). The genes were found to hybridize with genes for
      components of the modified ortho cleavage pathway from Pseudomonas putida. In one
      of the 3-CB-negative segregants, the plasmid had undergone the deletion of a
      segment with a size of about 12.5 kb that covered the catabolic genes. The
      deletion event seemed to be the result of reciprocal recombination between two
      highly homologous sequences with sizes of 2.5 kb that were present as a direct
      repeat at the two ends of the region that included the catabolic genes.
      Nucleotide sequence analysis of homologous fragments revealed a structure that
      resembled an insertion sequence and relatedness to IS21. During repeated
      subculturing of NH9 on liquid media with 3-CB, the culture was taken over by a
      derivative strain (designated NH9A) in which the degradative plasmid carried a
      duplicate copy of the 12.5-kb region that contained the catabolic genes. The
      duplication of these genes seemed again to have been mediated by recombination
      between the direct repeat sequences.

PMID- 8526488
TI  - Chorismate mutase and 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase of the
      methylotrophic actinomycete Amycolatopsis methanolica.
AB  - Chorismate mutase (CM) and 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP)
      synthase (DS) are key regulatory enzymes in L-Phe and L-Tyr biosynthesis in
      Amycolatopsis methanolica. At least two CM proteins, CMIa and CMIb, are required
      for the single chorismate mutase activity in the wild type. Component CMIa (a
      homodimeric protein with 16-kDa subunits) was purified to homogeneity (2,717
      fold) and kinetically characterized. The partially purified CMIb preparation
      obtained also contained the single DS (DSI) activity detectable in the wild type.
      The activities of CMIa and CMIb were inhibited by both L-Phe and L-Tyr. DSI
      activity was inhibited by L-Trp, L-Phe, and L-Tyr. A leaky L-Phe-requiring
      auxotroph, mutant strain GH141, grown under L-Phe limitation, possessed
      additional DS (DSII) and CM (CMII) activities. Synthesis of both CMII and DSII
      was repressed by L-Phe. An ortho-DL-fluorophenylalanine-resistant mutant of the
      wild type (strain oFPHE83) that had lost the sensitivity of DSII and CMII
      synthesis to L-Phe repression was isolated. DSII was partially purified (a 42-kDa
      protein); its activity was strongly inhibited by L-Tyr. CMII was purified to
      homogeneity (93.6 fold) and characterized as a homodimeric protein with 16-kDa
      subunits, completely insensitive to feedback inhibition by L-Phe and L-Tyr. The
      activity of CMII was activated by CMIb; the activity of CMII plus CMIb was again
      inhibited by L-Phe and L-Tyr. A tightly blocked L-Phe- plus L-Tyr-requiring
      derivative of mutant strain GH141, GH141-19, that had lost both CMIa and CMII
      activities was isolated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526489
TI  - Microbial degradation of monoterpenes in the absence of molecular oxygen.
AB  - Anaerobic degradation of natural monoterpenes by microorganisms was evaluated by
      using Pseudomonas citronellolis DSM 50332 and enrichment cultures containing
      nitrate as an electron acceptor. P. citronellolis grew anaerobically on 3,7
      dimethyl-1-octanol and citronellol but not on geraniol, nerol, and alicyclic
      monoterpenes. In contrast, several a-, mono-, and bicyclic monoterpenes supported
      microbial growth and denitrification in enrichment cultures. We found that
      consumption of linalool, menthol, menth-1-ene, alpha-phellandrene, limonene, 2
      carene, alpha-pinene, and fenchone in enrichment cultures depended on the
      presence of living microorganisms and nitrate. In these experiments, the ratios
      of number of electrons derived from complete substrate oxidation to number of
      electrons derived from nitrate reduction ranged from 1.2:1 to 2.9:1. Microbial
      degradation was accompanied by the formation of small traces of monoterpenes,
      which were characterized by gas chromatography-mass spectroscopy. The formation
      of geraniol and geranial from linalool suggested that a 3,1-hydroxyl-delta 1
      delta 2-mutase reaction initiates linalool degradation. Seven strains of motile,
      oval to rod-shaped, facultatively denitrifying bacteria were isolated on agar
      bottle plates by using linalool, menthol, menth-1-ene, alpha-phellandrene, 2
      carene, eucalyptol, and alpha-pinene as sole carbon and energy sources.

PMID- 8526490
TI  - Optimizing conditions for the growth of Lactobacillus casei YIT 9018 in tryptone
      yeast extract-glucose medium by using response surface methodology.
AB  - This study was undertaken to find optimum conditions of tryptone, yeast extract,
      glucose, Tween 80, and incubation temperature for the growth of Lactobacillus
      casei YIT 9018 and to assess the effects of these factors by use of response
      surface methodology. A central composite design was used as an experimental
      design for allocation of treatment combinations. A second-order polynomial
      regression model, which was used at first for analysis of the experiment, had a
      significant lack of fit. Therefore, cubic and quartic terms were incorporated
      into the regression model through variable selection procedures. Effects
      involving incubation temperature, yeast extract, glucose, and tryptone were
      significant, whereas the only significant effect involving Tween 80 was the
      interaction effect between temperature and Tween 80. It turned out that growth of
      L. casei YIT 9018 was most strongly affected by the incubation temperature.
      Estimated optimum conditions of the factors for growth of L. casei YIT 9018 are
      as follows: tryptone, 3.04%; yeast extract, 0.892%; glucose, 1.58%; Tween 80, 0%;
      incubation temperature, 35 degrees C.

PMID- 8526491
TI  - Production of volatile sesquiterpenes by Fusarium sambucinum strains with
      different abilities to synthesize trichothecenes.
AB  - Twenty-five strains of Fusarium sambucinum grown on wheat kernels were examined
      for trichothecene production and the synthesis of volatile sesquiterpenes. The
      volatiles were purged with air and collected on Tenax traps. Adsorbed compounds
      were eluted from the traps and injected into a gas chromatograph coupled with a
      mass spectrometer. Ten strains isolated from potato tubers produced high amounts
      of diacetoxyscirpenol and its derivatives. These strains were characterized by
      the production of high amounts of diverse sesquiterpenes. In 10 cultures, 19
      compounds were detected, of which 6 were predominant and composed as much as 82%
      of the volatile sesquiterpene fraction (e.g., beta-farnesene, beta-chamigrene,
      beta-bisabolene, alpha-farnesene, trichodiene, and an unidentified compound).
      Fifteen strains isolated from various sources that did not produce trichothecenes
      produced much less volatile sesquiterpenes, with less chemical diversity. No more
      than six compounds were present in cultures. Two of these compounds were present
      in the toxigenic strains isolated from potatoes (beta-farnesene and acoradiene),
      but four were unique to the strains not producing trichothecenes (longifolene,
      isocaryophyllene, delta-elemene, and an unidentified one). The pattern of
      volatile sesquiterpenes was characteristic and distinctive for both toxic and
      nontoxic strains.

PMID- 8526492
TI  - Development of a gene reporter system in moderately halophilic bacteria by
      employing the ice nucleation gene of Pseudomonas syringae.
AB  - The expression of the ice nucleation gene inaZ of Pseudomonas syringae in several
      moderate halophiles was investigated to establish its utility as a reporter for
      promoter activity and gene expression studies in these biotechnologically and
      environmentally important bacteria. A promoterless version of inaZ was introduced
      in two different restriction sites and at both orientations in a recombinant
      plasmid able to replicate in moderate halophiles and, in particular, within the
      sequence of its pHE1 part, a native plasmid of Halomonas elongata. One
      orientation of both recombinant constructs expressed high levels of ice
      nucleation activity in H. elongata and Volcaniella eurihalina cells, indicating
      that inaZ was probably introduced in the correct orientation downstream of
      putative native promoters. A recombinant construct carrying a tandem duplication
      of inaZ at the same orientation gave significantly higher ice nucleation
      activity, showing that inaZ is appropriate for gene dosage studies. The ice
      nucleation gene was also expressed in H. elongata and V. eurihalina under the
      control of Pbla (the promoter of the beta-lactamase gene of Escherichia coli) and
      Ppdc (the promoter of the pyruvate decarboxylase gene of Zymomonas mobilis). One
      of the inaZ reporter plasmids expressing high levels of ice nucleation activity
      under the control of a native putative promoter was also transferred in Halomonas
      subglaciescola, Halomonas meridiana, Halomonas halodurans, and Deleya halophila.
      In all cases, Ice+ transconjugants were successfully isolated, demonstrating that
      inaZ is expressed in a wide spectrum of moderately halophilic species.

PMID- 8526493
TI  - Specific PCR primers directed to identify cryI and cryIII genes within a Bacillus
      thuringiensis strain collection.
AB  - In this paper we describe a PCR strategy that can be used to rapidly identify
      Bacillus thuringiensis strains that harbor any of the known cryI or cryIII genes.
      Four general PCR primers which amplify DNA fragments from the known cryI or
      cryIII genes were selected from conserved regions. Once a strain was identified
      as an organism that contains a particular type of cry gene, it could be easily
      characterized by performing additional PCR with specific cryI and cryIII primers
      selected from variable regions. The method described in this paper can be used to
      identify the 10 different cryI genes and the five different cryIII genes. One
      feature of this screening method is that each cry gene is expected to produce a
      PCR product having a precise molecular weight. The genes which produce PCR
      products having different sizes probably represent strains that harbor a
      potentially novel cry gene. Finally, we present evidence that novel crystal genes
      can be identified by the method described in this paper.

PMID- 8526494
TI  - Resistance to Bacillus thuringiensis CryIA delta-endotoxins in a laboratory
      selected Heliothis virescens strain is related to receptor alteration.
AB  - The Bacillus thuringiensis toxin-binding properties of midgut epithelial cells
      from two strains of Heliothis virescens were compared. One H. virescens strains
      (YHD2) which was selected against CryIAc toxin had over 10,000-fold resistance to
      CryIAc toxin relative to the susceptible strain and was cross-resistant to CryIAa
      and CryIAb. The second H. virescens strain (YDK) was susceptible to these toxins
      in the order CryIAc > CryIAb > CryIAa. Receptor-binding properties of CryIAa,
      CryIAb, and CryIAc toxins were compared between the susceptible and resistant
      strains. Saturation and competition-binding experiments were performed with brush
      border membrane vesicles prepared from midguts of the susceptible and resistant
      insects and 125I-labeled toxins. In the susceptible strain, saturable, specific,
      and high-affinity binding of all three toxins was observed. The relative binding
      site concentration was directly correlated with toxicity (CryIAc > CryIAb >
      CryIAa). In the resistant strains, the binding affinities of CryIAb and CryIAc
      were similar to that observed with the susceptible strain and ony minor
      differences in binding-site concentration (Bmax) were observed. The major
      difference between the two strains was the total lack of binding of CryIAa toxin
      to the brush border membrane vesicles of the resistant strain. Heterologous
      competition-binding experiments and ligand blot analysis supported the hypothesis
      that there were multiple binding sites for the toxins. On the basis of results of
      the present study, we propose that alterations in binding proteins shared by all
      three toxins are a major factor in resistance. This suggests that not all
      receptors of CryIAc might be involved in toxic function.

PMID- 8526495
TI  - Characterization and transcriptional analysis of the gene cluster for coronafacic
      acid, the polyketide component of the phytotoxin coronatine.
AB  - Coronafacic acid (CFA), the polyketide component of the phytotoxin coronatine
      (COR), is activated and coupled to coronamic acid via amide bond formation, a
      biosynthetic step presumably catalyzed by the CFA ligase (cfl) gene product. The
      COR biosynthetic gene cluster in Pseudomonas syringae pv. glycinea PG4180 is
      located within a 32-kb region of a 90-kb plasmid designated p4180A. In the
      present study, a cloned region of p4180A complemented all CFA- mutants spanning
      an 18.8-kb region of the COR biosynthetic cluster. The genetic evidence presented
      in this study indicates that cfl and the CFA biosynthetic gene cluster are
      encoded by a single transcript and that transcription of all of the genes in this
      operon is directed by the cfl promoter. The cfl promoter was localized to a 0.37
      kb region upstream of the transcriptional start site by progressive subcloning in
      pRG960sd, a vector containing a promoterless glucuronidase gene. Transcription of
      the cfl/CFA operon was temperature sensitive and showed maximal glucuronidase
      activity at 18 degrees C. Furthermore, transcription of the cfl/CFA operon was
      dependent on the functional activity of a modified two-component regulatory
      system located within the COR biosynthetic gene cluster. Thermoregulation of the
      cfl/CFA operon and the coronamic acid biosynthetic gene cluster via the modified
      two-component regulatory system is discussed.

PMID- 8526496
TI  - Development of a PCR protocol for sensitive detection of Cryptosporidium oocysts
      in water samples.
AB  - The development of a reliable method of using PCR for detection of
      Cryptosporidium oocysts in environmental samples with oligonucleotide primers
      which amplify a portion of the sequence encoding the small (18S) subunit of rRNA
      producing a 435-bp product was demonstrated. The PCR assay was found to provide
      highly genus-specific detection of Cryptosporidium spp. after release of nucleic
      acids from oocysts by a simple freeze-thaw procedure. The assay routinely
      detected 1 to 10 oocysts in purified oocyst preparations, as shown by direct
      microscopic counts and by an immunofluorescence assay. The sensitivity of the PCR
      assay in some seeded environmental water samples was up to 1,000-fold lower.
      However, this interference was eliminated by either flow cytometry or magnetic
      antibody capture. Sensitivity was also improved 10- to 1,000-fold by probing of
      the PCR product on dot blots with an oligonucleotide probe detected by
      chemiluminescence. Confirmation of the presence of Cryptosporidium oocysts in
      water samples from the outbreak in Milwaukee, Wis., was obtained with this
      technique, and PCR was found to be as sensitive as immunofluorescence for
      detection of oocysts in wastewater concentrates.

PMID- 8526497
TI  - Tn5-directed cloning of pqq genes from Pseudomonas fluorescens CHA0: mutational
      inactivation of the genes results in overproduction of the antibiotic
      pyoluteorin.
AB  - Pseudomonas fluorescens CHA0 produces several secondary metabolites, e.g., the
      antibiotics pyoluteorin (Plt) and 2,4-diacetylphloroglucinol (Phl), which are
      important for the suppression of root diseases caused by soil-borne fungal
      pathogens. A Tn5 insertion mutant of strain CHA0, CHA625, does not produce Phl,
      shows enhanced Plt production on malt agar, and has lost part of the ability to
      suppress black root rot in tobacco plants and take-all in wheat. We used a rapid,
      two-step cloning-out procedure for isolating the wild-type genes corresponding to
      those inactivated by the Tn5 insertion in strain CHA625. This cloning method
      should be widely applicable to bacterial genes tagged with Tn5. The region cloned
      from P. fluorescens contained three complete open reading frames. The deduced
      gene products, designated PqqFAB, showed extensive similarities to proteins
      involved in the biosynthesis of pyrroloquinoline quinone (PQQ) in Klebsiella
      pneumoniae, Acinetobacter calcoaceticus, and Methylobacterium extorquens. PQQ
      negative mutants of strain CHA0 were constructed by gene replacement. They lacked
      glucose dehydrogenase activity, could not utilize ethanol as a carbon source, and
      showed a strongly enhanced production of Plt on malt agar. These effects were all
      reversed by complementation with pqq+ recombinant plasmids. The growth of a pqqF
      mutant on ethanol and normal Plt production were restored by the addition of 16
      nM PQQ. However, the Phl- phenotype of strain CHA625 was due not to the pqq
      defect but presumably to a secondary mutation. In conclusion, a lack of PQQ
      markedly stimulates the production of Plt in P. fluorescens.

PMID- 8526498
TI  - Division of Listeria monocytogenes serovar 4b strains into two groups by PCR and
      restriction enzyme analysis.
AB  - Altogether, 133 strains of Listeria monocytogenes serovar 4b were investigated. A
      segment of 2,916 bp containing parts of the two genes inlA and inlB in L.
      monocytogenes was amplified by the PCR technique. The PCR product obtained was
      cleaved with the restriction enzyme AluI, and the fragments generated were
      separated by gel electrophoresis, leading to two distinct groups: PCR-restriction
      enzyme analysis groups I and II, containing 37 and 96 strains, respectively. The
      PCR-restriction enzyme analysis method described in this paper could be a useful
      tool for the subtyping of L. monocytogenes serovar 4b strains.

PMID- 8526499
TI  - Genetic diversity and phylogeny of toxic cyanobacteria determined by DNA
      polymorphisms within the phycocyanin locus.
AB  - Cyanobacteria are a highly diverse group in relation to form, function, and
      habitat. Current cyanobacterial systematics relies on the observation of minor
      and plastic morphological characters. Accurate and reliable delineation of toxic
      and bloom-forming strains of cyanobacteria has not been possible by traditional
      methods. We have designed general primers to the phycocyanin operon (cpc gene)
      and developed a PCR which allows the amplification of a region of this gene,
      including a variable intergenic spacer sequence. Because of the specificity of
      this PCR for cyanobacterial isolates, the assay is appropriate for the rapid and
      reliable identification of strains in freshwater samples. Successive restriction
      endonuclease digestion of this amplification product, with a total of nine
      enzymes, yielded many identifying DNA profiles specific to the various taxonomic
      levels of cyanobacteria. The restriction enzyme profiles for MspI, RsaI, and TaqI
      were conserved for strains within each of the eight genera (40 strains) studied
      and clearly discriminated among these genera. Intrageneric delineation of strains
      was revealed by the enzymes AluI, CfoI, and HaeIII for members of the genus
      Microcystis, while strains of genus Anabaena were differentiated by the digestion
      patterns provided by AluI, CfoI, and ScrFI. Phenetic and cladistic analyses of
      the data were used to infer the genetic relatedness and evolution of toxic and
      bloom-forming cyanobacteria.

PMID- 8526500
TI  - Degradation of 1,4-dichlorobenzene by Xanthobacter flavus 14p1.
AB  - Xanthobacter flavus 14p1 was isolated from sludge of the river Mulde by selective
      enrichment with 1,4-dichlorobenzene as the sole source of carbon and energy. The
      bacterium did not use other aromatic or chloroaromatic compounds as growth
      substrates. During growth on 1,4-dichlorobenzene, stoichiometric amounts of
      chloride ions were released. Degradation products of 1,4-dichlorobenzene were
      identified by gas chromatography-mass spectrometry analysis. 3,6-Dichloro-cis-1,2
      dihydroxycyclohexa-3,5-diene and 3,6-dichlorocatechol were isolated from culture
      fluid. 2,5-Dichloromuconic acid and 2-chloromaleylacetic acid as well as the
      decarboxylation product 2-chloroacetoacrylic acid were identified after enzymatic
      conversion of 3,6-dichlorocatechol by cell extract. 1,4-Dichlorobenzene
      dioxygenase, dihydrodiol dehydrogenase, and catechol 1,2-dioxygenase activity
      were induced in cells grown on 1,4-dichlorobenzene. The results demonstrate that
      1,4-dichlorobenzene degradation is initiated by dioxygenation and that ring
      opening proceeds via ortho cleavage.

PMID- 8526501
TI  - Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in
      granular sludge.
AB  - N-substituted aromatics are important priority pollutants entering the
      environment primarily through anthropogenic activities associated with the
      industrial production of dyes, explosives, pesticides, and pharmaceuticals.
      Anaerobic treatment of wastewaters discharged by these industries could
      potentially be problematical as a result of the high toxicity of N-substituted
      aromatics. The objective of this study was to examine the structure-toxicity
      relationships of N-substituted aromatic compounds to acetoclastic methanogenic
      bacteria. The toxicity was assayed in serum flasks by measuring methane
      production in granular sludge. Unacclimated cultures were used to minimize the
      biotransformation of the toxic organic chemicals during the test. The nature and
      the degree of the aromatic substitution were observed to have a profound effect
      on the toxicity of the test compound. Nitroaromatic compounds were, on the
      average, over 500-fold more toxic than their corresponding aromatic amines.
      Considering the facile reduction of nitro groups by anaerobic microorganisms, a
      dramatic detoxification of nitroaromatics towards methanogens can be expected to
      occur during anaerobic wastewater treatment. While the toxicity exerted by the N
      substituted aromatic compounds was closely correlated with compound apolarity
      (log P), it was observed that at any given log P, N-substituted phenols had a
      toxicity that was 2 orders of magnitude higher than that of chlorophenols and
      alkylphenols. This indicates that toxicity due to the chemical reactivity of
      nitroaromatics is much more important than partitioning effects in bacterial
      membranes.

PMID- 8526503
TI  - Degradation of 4,4'-dichlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, and
      2,2',4,4',5,5'-hexachlorobiphenyl by the white rot fungus Phanerochaete
      chrysosporium.
AB  - The white rot fungus Phanerochaete chrysosporium has demonstrated abilities to
      degrade many xenobiotic chemicals. In this study, the degradation of three model
      polychlorinated biphenyl (PCB) congeners (4,4'-dichlorobiphenyl [DCB], 3,3',4,4'
      tetrachlorobiphenyl, and 2,2',4,4',5,5'-hexachlorobiphenyl) by P. chrysosporium
      in liquid culture was examined. After 28 days of incubation, 14C partitioning
      analysis indicated extensive degradation of DCB, including 11% mineralization. In
      contrast, there was negligible mineralization of the tetrachloro- or
      hexachlorobiphenyl and little evidence for any significant metabolism. With all
      of the model PCBs, a large fraction of the 14C was determined to be biomass
      bound. Results from a time course study done with 4,4'-[14C]DCB to examine 14C
      partitioning dynamics indicated that the biomass-bound 14C was likely
      attributable to nonspecific adsorption of the PCBs to the fungal hyphae. In a
      subsequent isotope trapping experiment, 4-chlorobenzoic acid and 4-chlorobenzyl
      alcohol were identified as metabolites produced from 4,4'-[14C]DCB. To the best
      of our knowledge, this the first report describing intermediates formed by P.
      chrysosporium during PCB degradation. Results from these experiments suggested
      similarities between P. chrysosporium and bacterial systems in terms of effects
      of congener chlorination degree and pattern on PCB metabolism and intermediates
      characteristic of the PCB degradation process.

PMID- 8526502
TI  - Isolation and characterization of genetically engineered gallidermin and
      epidermin analogs.
AB  - Gallidermin (Gdm) and epidermin (Epi) are highly homologous tetracyclic
      polypeptide antibiotics that are ribosomally synthesized by a Staphylococcus
      gallinarum strain and a Staphylococcus epidermidis strain, respectively. These
      antibiotics are secreted into media and are distinguished by the presence of the
      unusual amino acids lanthionine, 3-methyllanthionine, didehydrobutyrine, and S-(2
      aminovinyl)-D-cysteine, which are formed by posttranslational modification. To
      study the substrate specificities of the modifying enzymes and to obtain variants
      that exhibit altered or new biological activities, we changed certain amino acids
      by performing site-specific mutagenesis with the Gdm and Epi structural genes
      (gdmA and epiA, respectively). S. epidermidis Tu3298/EMS6, an epiA mutant of the
      Epi-producing strain, was used as the expression host. This mutant synthesized
      Epi, Gdm, or analogs of these antibiotics when the appropriate genes were
      introduced on a plasmid. No Epi or Gdm analogs were isolated from the supernatant
      when (i) hydroxyamino acids involved in thioether amino acid formation were
      replaced by nonhydroxyamino acids (S3N and S19A); (ii) C residues involved in
      thioether bridging were deleted (delta C21, C22 and delta C22); or (iii) a ring
      amino acid was replaced by an amino acid having a completely different character
      (G10E and Y20G). A strong decrease in production was observed when S residues
      involved in thioether amino acid formation were replaced by T residues (S16T and
      S19T). A number of conservative changes at positions 6, 12, and 14 on the Gdm
      backbone were tolerated and led to analogs that had altered biological
      properties, such as enhanced antimicrobial activity (L6V) or a remarkable
      resistance to proteolytic degradation (A12L and Dhb14P). The T14S substitution
      led to simultaneous production of two Gdm species formed by incomplete
      posttranslational modification (dehydration) of the S-14 residue. The fully
      modified Dhb14Dha analog exhibited antimicrobial activity similar to that of Gdm,
      whereas the Dhb14S analog was less active. Both peptides were more sensitive to
      tryptic cleavage than Gdm was.

PMID- 8526504
TI  - Involvement of an extracellular H2O2-dependent ligninolytic activity of the white
      rot fungus Pleurotus ostreatus in the decolorization of Remazol brilliant blue R.
AB  - During solid-state fermentation of wheat straw, a natural lignocellulosic
      substrate, the white rot fungus Pleurotus ostreatus produced an extracellular
      H2O2-requiring Remazol brilliant blue R (RBBR)-decolorizing enzymatic activity
      along with manganese peroxidase, manganese-independent peroxidase, and phenol
      oxidase activities. The presence of RBBR was not essential for the production of
      RBBR-decolorizing enzymatic activity by P. ostreatus, because this activity was
      also produced in the absence of RBBR. This RBBR-decolorizing enzymatic activity
      in crude enzyme preparations of 14- and 20-day-old cultures exhibited an apparent
      Km for RBBR of 31 and 52 microM, respectively. The RBBR-decolorizing enzyme
      activity was maximal in the pH range 3.5 to 4.0. This activity was independent of
      manganese, and veratryl alcohol had no influence on it. Manganese peroxidase of
      P. ostreatus did not decolorize RBBR. This H2O2-dependent RBBR-decolorizing
      enzymatic activity behaved like an oxygenase possessing a catalytic metal center,
      perhaps heme, because it was inhibited by Na2S2O5, NaCN, NaN3, and depletion of
      dissolved oxygen. Na2S2O5 brought an early end to the reaction without
      interfering with the initial reaction rate of RBBR oxygenase. The activity was
      also inhibited by cysteine. Concentrations of H2O2 higher than 154 microM were
      observed to be inhibitory as well. Decolorization of RBBR by P. ostreatus is an
      oxidative process.

PMID- 8526505
TI  - Characterization of an H2-utilizing enrichment culture that reductively
      dechlorinates tetrachloroethene to vinyl chloride and ethene in the absence of
      methanogenesis and acetogenesis.
AB  - We have been studying an anaerobic enrichment culture which, by using methanol as
      an electron donor, dechlorinates tetrachloroethene (PCE) to vinyl chloride and
      ethene. Our previous results indicated that H2 was the direct electron donor for
      rductive dechlorination of PCE by the methanol-PCE culture. Most-probable-number
      counts performed on this culture indicated low numbers (< or equal to 10(4)/ml))
      of methanogens and PCE dechlorinators using methanol and high numbers (> or equal
      to 10(6)/ml)) of sulfidogens, methanol-utilizing acetogens, fermentative
      heterotrophs, and PCE dechlorinators using H2. An anaerobic H2-PCE enrichment
      culture was derived from a 10(-6) dilution of the methanol-PCE culture. This H2
      PCE culture used PCE at increasing rates over time when transferred to fresh
      medium and could be transferred indefinitely with H2 as the electron donor for
      the PCE dechlorination, indicating that H2-PCE can serve as an electron donor
      acceptor pair for energy conservation and growth. Sustained PCE dechlorination by
      this culture was supported by supplementation with 0.05 mg of vitamin B12 per
      liter, 25% (vol/vol) anaerobic digestor sludge supernatant, and 2 mM acetate,
      which presumably served as a carbon source. Neither methanol nor acetate could
      serve as an electron donor for dechlorination by the H2-PCE culture, and it did
      not produce CH4 or acetate from H2-CO2 or methanol, indicating the absence of
      methanogenic and acetogenic bacteria. Microscopic observatios of the pruified H2
      PCE culture showed only two major morphotypes: irregular cocci and small rods.

PMID- 8526506
TI  - Involvement of enzyme-substrate charge interactions in the caseinolytic
      specificity of lactococcal cell envelope-associated proteinases.
AB  - Three series of oligopeptides were synthesized to investigate the proposal that a
      major factor in determining the differences in specificity of the lactococcal
      cell surface-associated proteinases against caseins is the interactions between
      charged amino acids in the substrate and in the enzyme. The sequences of the
      oligopeptides were based on two regions of kappa-casein (residues 98 to 111 and
      153 to 169) which show markedly different susceptibilities to PI- and PIII-type
      lactococcal proteinases. In each series, one oligopeptide had an identical
      sequence to that of the kappa-casein region, while in the others, one or more
      charged residues were substituted by an amino acid of opposite charge, i.e., His<
      ->Glu. Generally, substitution of His by Glu in the oligopeptides corresponding
      to residues 98 to 111 of kappa-casein resulted in reduced cleavage of susceptible
      bonds by the PI-type proteinase and increased cleavage of susceptible bonds by
      the PIII-type proteinase. In the case of the oligopeptide corresponding to
      residues 153 to 169 of kappa-casein, one major cleavage site was evident, and the
      bond was hydrolyzed by both types of proteinase (even though this sequence in
      kappa-casein itself is extremely resistant to the PI-type enzyme). Substitution
      of Glu by His in this oligopeptide, even in the P7 position, resulted in
      increased cleavage of the bond by the PI-type proteinase and reduced cleavage by
      the PIII-type proteinase. C-terminal truncation of this oligopeptide resulted in
      a 100-fold decrease in the rate of hydrolysis of the susceptible bond and a
      change in the pattern of cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526507
TI  - Comparative evaluation of modified m-FC and m-TEC media for membrane filter
      enumeration of Escherichia coli in water.
AB  - Two media used to detect fecal coliforms in water by membrane filtration, m-FC
      and m-TEC, were modified and supplemented with the chromogenic substrate 5-bromo
      6-chloro-3-indoyl-beta-D-glucuronide (BCIG) and were compared for quantitative
      recovery of Escherichia coli. Student's t test of data from 181 water samples of
      sewage, rivers, lakes, and wells did not demonstrate any statistically
      significant differences (P = 0.05) in the enumeration of E. coli with these
      media. Target colonies were confirmed to be E. coli at rates of 98.6 and 97.3% by
      using FC-BCIG and TEC-BCIG media, respectively. Glucuronidase-negative isolates
      of E. coli were encountered at the same frequency (6.0%) on both media. This
      collaborative study demonstrated that either modified basal medium could be used
      successfully for detection of E. coli in various nontreated waters within 24 h.

PMID- 8526508
TI  - A microsatellite marker for studying the ecology and diversity of fungal
      endophytes (Epichloe spp.) in grasses.
AB  - Randomly amplified polymorphic DNA fingerprinting, which is based on PCR with
      arbitrary 10-nucleotide primers, were used to analyze genetic diversity among
      isolates of the endophytic ascomycete Epichloe typhina, which were collected at a
      single field site from a population of one of its hosts, the grass Bromus
      erectus. One of the polymorphic randomly amplified polymorphic DNA PCR products
      occurred in all isolates as single bands with different but closely related
      sizes. Two of the size variants of this product were cloned and sequenced, and
      they were found to represent the same DNA sequence, except for a stretch of
      tandem repeats of the trinucleotide AAG.TTC, which differed in size, consisting
      of 8 and 18 repeats, respectively. Tandem repeats of this type are called
      microsatellites. Oligonucleotides were synthesized corresponding to portions of
      the sequence flanking the microsatellite and were used for PCR amplification of
      the loci from the genomic DNAs of different Epichloe isolates. A single PCR
      product was found for most isolates, indicating that the sequence represented a
      single genetic locus. Five alleles that could clearly be distinguished in size
      were found in a population of 91 field isolates. PCR with (AAC)8 and (AAG)8 as
      primers yielded a number of amplified bands from genomic DNA of Epichloe
      isolates, indicating that these types of microsatellites occur frequently in the
      genome of this fungus. A survey of all fungal DNA sequences currently deposited
      in the DNA sequence databases of EMBL and GenBank revealed that microsatellites
      of different repeating units are widespread in fungi.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8526509
TI  - Genotyping male-specific RNA coliphages by hybridization with oligonucleotide
      probes.
AB  - F-specific (F+) RNA coliphages are prevalent in sewage and other fecal wastes of
      humans and animals. There are four antigenically distinct serogroups of F+ RNA
      coliphages, and those predominating in humans (groups II and III) differ from
      those predominating in animals (groups I and IV). Hence, it may be possible to
      distinguish between human and animal wastes by serotyping F+ RNA coliphage
      isolates. Because serotyping is laborious and requires scarce antiserum reagents,
      we investigated genotyping using synthetic oligonucleotide probes as an
      alternative approach to distinguishing the four groups of F+ RNA coliphages.
      Oligoprobes I, II, III, IV, A, and B were selected to detect group I, II, III,
      IV, I plus II, and III plus IV phages, respectively. Methods for phage transfer
      from zones of lysis on a host cell lawn to candidate membrane filters and
      fixation of genomic nucleic acid on the membranes were optimized. The
      oligoprobes, which were end labeled with digoxigenin, were applied in DNA-RNA
      hybridization, and hybrids were observed by colorimetric, immunoenzymatic
      detection. Of 203 isolates of F+ RNA coliphages from environmental samples of
      water, wastes, and shellfish, 99.5 and 96.6% could be classified into each group
      by serotyping and genotyping, respectively. Probes A and B correctly identified
      100% of the isolates. On the basis of these results, this method for genotyping
      F+ RNA coliphages appears to be practical and reliable for typing isolates in
      field samples.

PMID- 8526510
TI  - Metabolic engineering of Lactococcus lactis: influence of the overproduction of
      alpha-acetolactate synthase in strains deficient in lactate dehydrogenase as a
      function of culture conditions.
AB  - The als gene for alpha-acetolactate synthase of Lactococcus lactis MG1363 was
      cloned on a multicopy plasmid under the control of the inducible L. lactis lacA
      promoter. More than a hundredfold overproduction of alpha-acetolactate synthase
      was obtained in L. lactis under inducing conditions as compared with that of the
      host strain, which contained a single chromosomal copy of the als gene. The
      effect of alpha-acetolactate synthase overproduction on the formation of end
      products in various L. lactis strains was studied under different fermentation
      conditions. Under aerobic conditions and with an initial pH of 6.0,
      overexpression of the als gene resulted in significant acetoin production that
      amounted to more than one-third of the pyruvate converted. However, the effect of
      the alpha-acetolactate synthase overproduction was even more pronounced in the
      lactate dehydrogenase-deficient strain L. lactis NZ2700. Anaerobic cultivation of
      this strain resulted in a doubling of the butanediol formation of up to 40% of
      the converted pyruvate. When cultivated aerobically at an initial pH of 6.8,
      overexpression of the als gene in L. lactis NZ2700 resulted in the conversion of
      more than 60% of the pyruvate into acetoin, while no butanediol was formed.
      Moreover, at an initial pH of 6.0, similar amounts of acetoin were obtained, but
      in addition approximately 20% of the pyruvate was converted into butanediol.
      These metabolic engineering studies indicate that more than 80% of the lactose
      can be converted via the activity of the overproduced alpha-acetolactate synthase
      in L. lactis.

PMID- 8526511
TI  - Direct DNA extraction for PCR-mediated assays of soil organisms.
AB  - By using the rDNA of a plant wilt pathogen (Verticillium dahliae) as the target
      sequence, a direct method for the extraction of DNA from soil samples which can
      be used for PCR-mediated diagnostics without a need for further DNA purification
      has been developed. The soil organisms are disrupted by grinding in liquid
      nitrogen with the natural abrasives in soil, and losses due to degradation and
      adsorption are largely eliminated by the addition of skim milk powder. The DNA
      from disrupted cells is extracted with sodium dodecyl sulfate-phenol and
      collected by ethanol precipitation. After suitable dilution, this DNA extract can
      be assayed directly by PCR amplification technologies. The method is rapid, cost
      efficient, and when combined with suitable internal controls can be applied to
      the detection and quantification of specific soil organisms or pathogens on a
      large-scale basis.

PMID- 8526512
TI  - Direct sequencing of hepatitis A virus strains isolated during an epidemic in
      France.
AB  - Direct sequencing of PCR products was used to study the VP1 region of the
      hepatitis A virus (HAV) genome (position 2199 to 2356) of nine strains isolated
      from human stools collected during a hepatitis A epidemic (western France, 1992),
      three strains from environmental samples (1990, 1991, and 1992), and two HAV cell
      culture isolates (the French strain CF53/Lyon and strain CLF). These viruses
      differed from CF53/Lyon (genotype I) by between 1 and 10.3%, and results
      indicated the existence of two groups of strains belonging to two different
      subgenotypes (IA and IB). With this sequencing technique it was possible to
      monitor the epidemiology of HAV and study its relations.

PMID- 8526513
TI  - Application of reverse transcriptase PCR for monitoring expression of the
      catabolic dmpN gene in a phenol-degrading sequencing batch reactor.
AB  - A modified freeze-thaw method in combination with reverse transcriptase PCR was
      developed for monitoring gene expression in activated sludge. The sensitivity of
      the methodology was determined by inoculating non-sterile activated sludge
      samples with 3-chlorobenzoate-degrading Pseudomonas putida PPO301(pRO103), which
      contains the catabolic tfdB gene. tfdB mRNA was detected in 10 mg of activated
      sludge inoculated with 10(4) CFU of the target organism. This technique was
      subsequently utilized to analyze the in situ expression of the catabolic dmpN
      gene in a sequencing batch reactor (SBR) bioaugmented with phenol-degrading P.
      putida ATCC 11172. Greatest dmpN expression was observed 15 min after maximum
      phenol concentration was reached in the reactor and 15 min after the start of
      aeration. Decreased phenol concentrations in the reactor corresponded to reduced
      levels of dmpN expression, although low levels of dmpN mRNA were observed
      throughout the SBR cycle. These results indicate that concentration of phenol in
      the reactor and the onset of aeration stimulated transcriptional activity of the
      dmpN gene. The information obtained from this study can be used to alter SBR
      operational strategies so as to lead to more effective bioaugmentation practices.

PMID- 8526514
TI  - Rhizobium tropici chromosomal citrate synthase gene.
AB  - Two genes encoding citrate synthase, a key enzyme in the Krebs cycle, have been
      found in Rhizobium tropici. One of them is in the bacterial chromosome, while the
      other is in the symbiotic plasmid. We sequenced the chromosomal gene and found
      that it is very similar to the previously reported plasmidic gene sequence in its
      structural region but not in its regulatory region. The chromosomal gene is able
      to complement an Escherichia coli citrate synthase mutant. In R. tropici, a
      mutant in the chromosomal citrate synthase gene has a diminished citrate synthase
      activity (in free-living bacteria), a diminished nodulation capacity, and forms
      nitrogen-fixing nodules. In contrast, the citrate synthase double mutant forms
      ineffective nodules devoid of bacteroids and forms less nodules than the single
      chromosomal mutant. It is inferred that both genes are functional and required
      during the nodulation process in R. tropici.

PMID- 8526515
TI  - Genetic and biochemical characterization of the Lactobacillus delbrueckii subsp.
      lactis bacteriophage LL-H lysin.
AB  - LL-H, a virulent phage of Lactobacillus delbrueckii subsp. lactis, produces a
      peptidoglycan-degrading enzyme, Mur, that is effective on L. delbrueckii,
      Lactobacillus acidophilus, Lactobacillus helveticus, and Pediococcus damnosus
      cell walls. In this study, the LL-H gene mur was cloned into Escherichia coli,
      its nucleotide sequence was determined, and the enzyme produced in E. coli was
      purified and biochemically characterized. Mur was purified 112-fold by means of
      ammonium sulfate precipitation and cation-exchange chromatography. The cell wall
      hydrolyzing activity was found to be associated with a 34-kDa protein. The C
      terminal domain of Mur is not essential for catalytic activity since it can be
      removed without destroying the lytic activity. The N-terminal sequence of the
      purified lysin was identical to that deduced from the nucleotide sequence, but
      the first methionine is absent from the mature protein. The N-terminal part of
      this 297-amino-acid protein had homology with several Chalaropsis-type lysozymes.
      Reduction of purified and Mur-digested L. delbrueckii cell wall material with
      labeled NaB3H4 indicated that the enzyme is a muramidase. The temperature optimum
      of purified Mur is between 30 and 40 degrees C, and the pH optimum is around 5.0.
      The LL-H lysin Mur is stable at temperatures below 60 degrees C.

PMID- 8526516
TI  - Production of galacto-oligosaccharide from lactose by Sterigmatomyces elviae
      CBS8119.
AB  - Our stock cultures were screened for microorganisms that can produce galacto
      oligosaccharide (Gal-OS) from lactose. Of the 574 strains of bacteria and yeasts
      tested, Sterigmatomyces elviae CBS8119, Rhodotorula minuta IFO879, and
      Sirobasidium magnum CBS6803 were found to be efficient producers of Gal-OS from
      lactose and S. elviae CBS8119 was selected as a representative, high-level
      producing strain. With toluene-treated resting S. elviae CBS8119 cells, 135 mg of
      Gal-OS per ml was produced from 360-mg/ml lactose. During this reaction, the by
      product glucose was found to inhibit Gal-OS production. Therefore, in order to
      remove the glucose from the reaction mixture, a culture method in which cell
      growth followed the enzymatic reaction was devised, which increased the yield of
      Gal-OS considerably because of the consumption of glucose for cell growth. Under
      such conditions, 232 mg of Gal-OS per ml was produced from 360-mg/ml lactose
      after incubation at 30 degrees for 60 h. The structure of the major product was
      identified as O-beta-D-galactopyranosyl-(1-->4)-O-beta-D-galactopyranosyl-(1-->4)
      D- glucopyranose (4'-galactosyl-lactose) by 13C nuclear magnetic resonance
      spectroscopy.

PMID- 8526517
TI  - Purification and properties of a novel thermostable galacto-oligosaccharide
      producing beta-galactosidase from Sterigmatomyces elviae CBS8119.
AB  - A thermostable beta-galactosidase which catalyzed the production of galacto
      oligosaccharide from lactose was solubilized from a cell wall preparation of
      Sterigmatomyces elviae CBS8119. The enzyme was purified to homogeneity by means
      of chromatography on DEAE-Toyopearl, Butyl-Toyopearl, Chromatofocusing, and p
      aminobenzyl 1-thio-beta-D-galactopyranoside agarose columns. The molecular weight
      of the purified enzyme was estimated to be about 170,000 by gel filtration with a
      Highload-Superdex 200pg column and 86,000 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Its isoelectric point, determined by
      polyacrylamide gel electrofocusing, was 4.1. The optimal temperature for enzyme
      activity was 85 degrees C. It was stable at temperatures up to 80 degrees C for 1
      h. The optimal pH range for the enzyme was 4.5 to 5.0, it was stable at pH 2.5 to
      7.0, and its activity was inhibited by Hg2+. The Km values for o-nitrophenyl-beta
      D-galactopyranoside and lactose were 9.5 and 2.4 mM, respectively, and the
      maximum velocities for these substrates were 96 and 240 mumol/min per mg of
      protein, respectively. In addition, this enzyme possessed a high level of
      transgalactosylation activity. Galacto-oligosaccharides, including tri- and
      tetrasaccharides, were produced with a yield, by weight, of 39% from 200-mg/ml
      lactose.

PMID- 8526518
TI  - Efficient expression of a 100-kilodalton mosquitocidal toxin in protease
      deficient recombinant Bacillus sphaericus.
AB  - The expression of the 100-kDa mosquitocidal toxin (Mtx) during vegetative growth
      and sporulation in nine different mosquito-larvicidal strains of Bacillus
      sphaericus has been analyzed. In five out of the nine strains the 100-kDa toxin
      was found to be expressed predominantly in the vegetative phase of growth, and in
      all nine strains the level of the toxin in sporulated cells was very low or
      undetectable. Strains in four out of the six DNA homology groups of B. sphaericus
      produced intracellular and extracellular proteases, which degraded the 100-kDa
      toxin, during sporulation. The 100-kDa toxin gene was expressed by using its
      native promoter on a multicopy number plasmid in B. sphaericus 1693 (protease
      negative) and B. sphaericus 13052 (protease positive). High levels of the 100-kDa
      toxin were produced in vegetative cells of both strains as well as in sporulated
      cells of protease-negative strain 1693, which is in contrast to the low levels of
      the 100-kDa toxin produced in sporulated cells of protease-positive strain 13052.
      Thus, the small amount of the 100-kDa toxin in sporulated cells of the nine
      mosquito-larvicidal strains is probably due to degradation of the 100-kDa toxin
      synthesized during vegetative growth by a protease(s) produced during
      sporulation. B. sphaericus 1693 transformed with the 100-kDa toxin gene was as
      toxic to mosquito larvae during both vegetative growth and sporulation as the
      natural high-toxicity strains of sporulated B. sphaericus.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8526519
TI  - The protoxin composition of Bacillus thuringiensis insecticidal inclusions
      affects solubility and toxicity.
AB  - Most Bacillus thuringiensis strains producing toxins active on lepidoptera
      contain several plasmid-encoded delta-endotoxin genes and package related
      protoxins into a single inclusion. It was previously found that in B.
      thuringiensis subsp. aizawai HD133, which produces an inclusion comprising the
      CryIAb, CryIC, and CryID protoxins, there is a spontaneous loss in about 1% of
      the cells of a 45-mDa plasmid containing the cryIAb gene. As a result, inclusions
      produced by the cured strain were less readily solubilized at pH 9.2 or 9.5 and
      had a decreased toxicity for Plodia interpunctella, despite the presence of the
      CryIC protoxin, which was active when solubilized. These results suggested that
      protoxin composition was a factor in inclusion solubility and toxicity and that
      the cryIAb gene, which is also present on an unstable plasmid in several other
      subspecies, may have a unique role in inclusion solubility and toxicity.
      Introduction of a cloned copy of this gene into the plasmid-cured derivative of
      B. thuringiensis subsp. aizawai HD133 resulted in an increase in the solubility
      at pH 9.2 of all of the inclusion proteins from less than 20% to greater than 45%
      and a lowering of the 50% lethal concentration (LC50, in micrograms [dry weight]
      per square centimeter) of inclusions for Spodoptera frugiperda from 35 to 10.
      These values are the same as those found with inclusions from B. thuringiensis
      subsp. aizawai HD133, and in all cases, the LC50 of the solubilized protoxins was
      10. Transformants containing related cryIA genes produced inclusions which were
      more than 95% solubilized at pH 9.2 but also had LC50 of 10.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8526520
TI  - Maintenance and induction of naphthalene degradation activity in Pseudomonas
      putida and an Alcaligenes sp. under different culture conditions.
AB  - The expression of xenobiotic-degradative genes in indigenous bacteria or in
      bacteria introduced into an ecosystem is essential for the successful
      bioremediation of contaminated environments. The maintenance of naphthalene
      utilization activity is studied in Pseudomonas putida (ATCC 17484) and an
      Alcaligenes sp. (strain NP-Alk) under different batch culture conditions. Levels
      of activity decreased exponentially in stationary phase with half-lives of 43 and
      13 h for strains ATCC 17484 and NP-Alk, respectively. Activity half-lives were
      2.7 and 5.3 times longer, respectively, in starved cultures than in stationary
      phase cultures following growth on naphthalene. The treatment of starved cultures
      with chloramphenicol caused a loss of activity more rapid than that measured in
      untreated starved cultures, suggesting a continued enzyme synthesis in starved
      cultures in the absence of a substrate. Following growth in nutrient medium,
      activity decreased to undetectable levels in the Alcaligenes sp. but remained at
      measurable levels in the pseudomonad even after 9 months. The induction of
      naphthalene degradation activities in these cultures, when followed by
      radiorespirometry with 14C-labeled naphthalene as the substrate, was consistent
      with activity maintenance data. In the pseudomonad, naphthalene degradation
      activity was present constitutively at low levels under all growth conditions and
      was rapidly (in approximately 15 min) induced to high levels upon exposure to
      naphthalene. Adaptation in the uninduced Alcaligenes sp. occurred after many
      hours of exposure to naphthalene. In vivo labeling with 35S, to monitor the
      extent of de novo enzyme synthesis by naphthalene-challenged cells, provided an
      independent confirmation of the results.

PMID- 8526521
TI  - In situ PCR for visualization of microscale distribution of specific genes and
      gene products in prokaryotic communities.
AB  - Obtaining information on the genetic capabilities and phylogenetic affinities of
      individual prokaryotic cells within natural communities is a high priority in the
      fields of microbial ecology, microbial biogeochemistry, and applied microbiology,
      among others. A method for prokaryotic in situ PCR (PI-PCR), a technique which
      will allow single cells within complex mixtures to be identified and
      characterized genetically, is presented here. The method involves amplification
      of specific nuclei acid sequences inside intact prokaryotic cells followed by
      color or fluorescence detection of the localized PCR product via bright-field or
      epifluorescence microscopy. Prokaryotic DNA and mRNA were both used successfully
      as targets for PI-PCR. We demonstrate the use of PI-PCR to identify nahA-positive
      cells in mixtures of bacterial isolates and in model marine bacterial
      communities.

PMID- 8526522
TI  - Differential secretion of isoforms of Serratia marcescens extracellular nuclease.
AB  - Extracellular secretion of the Serratia marcescens nuclease occurs in a two-step
      process: (i) rapidly to the periplasm via a signal sequence-dependent pathway and
      then (ii) slowly to the extracellular growth medium without cell lysis. There are
      two major isoforms of the nuclease in the culture supernatant of S. marcescens.
      We have isolated, purified, and determined the sequences of both isoforms. The
      first isoform, the mature nuclease (Sm2), is the result of signal sequence
      processing. The second isoform (Sm1) has three additional amino acids missing
      from the N terminus of the mature nuclease. Sm1 starts to appear extracellularly
      only during prolonged growth of a culture (16 to 48 h), probably because of cell
      lysis. However, pulse-chase experiments show that it is made early with Sm2 but
      is not secreted efficiently.

PMID- 8526523
TI  - Sequence analysis of the Lactococcus lactis temperate bacteriophage BK5-T and
      demonstration that the phage DNA has cohesive ends.
AB  - The Lactococcus lactis temperate bacteriophage BK5-T is a type phage in the
      lactococcal phage classification (A. W. Jarvis, G. F. Fitzgerald, M. Mata, A.
      Mercenier, H. Neve, I. B. Powell, C. Ronda, M. Saxelin, and M. Teuber,
      Intervirology 32:2-9, 1991). The nucleotide sequence of 18,935 bp of the genome
      of BK5-T was determined and analyzed for the presence of open reading frames and
      other structural features. Thirty-two open reading frames longer than 60 codons
      were identified, and these appeared to be grouped into at least seven
      transcriptional units. A search of the nucleotide sequence for restriction sites
      identified a small number of discrepancies with the previously published physical
      map of the BK5-T genome (G. Lakshmidevi, B. E. Davidson, and A. J. Hillier, Appl.
      Environ. Microbiol. 54:1039-1045, 1988). Subsequent analysis of restriction
      digests of BK5-T DNA which were heated prior to electrophoresis indicated that
      BK5-T DNA was not terminally redundant as previously reported but contained
      cohesive ends.

PMID- 8526524
TI  - Identification of prophage genes expressed in lysogens of the Lactococcus lactis
      bacteriophage BK5-T.
AB  - Bacteriophage BK5-T is a small isometric-headed temperate phage that infects
      Lactococcus lactis subsp. cremoris. Northern (RNA) analysis of mRNA produced by
      lysogenic strains containing BK5-T prophage revealed four major BK5-T transcripts
      that are 0.8, 1.3, 1.8, and 1.8 kb in size and enabled a transcription map of the
      prophage genome to be prepared. The position and size of each transcript
      corresponded closely to the position and size of open reading frames predicted
      from the nucleotide sequence of BK5-T. Analysis of the transcripts suggested that
      one of them was derived from the gene encoding the BK5-T integrase and another
      was from the gene encoding the BK5-T homolog of the lambda cI repressor. Computer
      analysis of the nucleotide sequence upstream of the BK5-T cI homolog predicted
      the presence of a pair of divergent promoters and three inverted repeat
      sequences, features characteristic of temperature-phage immunity regions. By
      analogy with lambda, the three inverted repeat sequences could be binding sites
      for cI or Cro homologs and the two divergent promoters could initiate
      transcription through the BK5-T equivalents of cI and cro.

PMID- 8526525
TI  - Spontaneous deletion mutants of the Lactococcus lactis temperate bacteriophage
      BK5-T and localization of the BK5-T attP site.
AB  - Spontaneous deletion mutants of the temperate lactococcal bacteriophage BK5-T
      were obtained when the phage was grown vegetatively on the indicator strain
      Lactococcus lactis subsp. cremoris H2. One deletion mutant was unable to form
      stable lysogens, and analysis of this mutant led to the identification of the BK5
      T attP site and the integrase gene (int). The core sequences of the BK5-T attP
      and host attB regions are conserved in a number of lactococcal phages and L.
      lactis strains.

PMID- 8526526
TI  - Sequence and expression of a xylanase gene from the hyperthermophile Thermotoga
      sp. strain FjSS3-B.1 and characterization of the recombinant enzyme and its
      activity on kraft pulp.
AB  - A gene expressing xylanase activity was isolated from a genomic library of
      Thermotoga sp. strain FjSS3-B.1. The sequence of the gene shows that it encodes a
      single domain, family 10 xylanase. The recombinant enzyme has extremely high
      thermal stability, activity over a relatively broad pH range, and activity on
      Pinus radiata kraft pulp.

PMID- 8526527
TI  - Highly efficient expression of fish growth hormone by Escherichia coli cells.
AB  - A PCR product encoding the mature segment of fish pregrowth hormone (pre-GH) was
      inserted into an Escherichia coli expression vector, pET, in which the ori site
      was replaced by that of pUC19. The yield of recombinant GH (rGH) was as high as
      44 to 47% of total protein. This rGH was immunoreactive to GH antibody. After
      renaturation, rGH was used to inject fish with 0.1 microgram of rGH per g once
      every 2 weeks, and this resulted in increases in weight (65%), percent weight
      gain (165%), and length (22%) relative to those of an untreated control group at
      week 16 and onward.

PMID- 8526528
TI  - A rapid method for extraction and purification of DNA from dental plaque.
AB  - A rapid method based on previously described DNA extraction procedures was
      developed for the isolation of DNA from dental plaque samples. The isolated DNA
      is suitable for use in the PCR. Freeze-thawing, cell wall-degrading enzymes, and
      guanidine isothiocyanate were used to lyse cells and release DNA. The released
      DNA was adsorbed onto diatomaceous earth and purified by washing with guanidine
      isothiocyanate, ethanol, and acetone. The purified DNA was released from the
      diatomaceous earth into an aqueous buffer and analyzed by PCR with 16S rDNA
      primers (rDNA is DNA coding for rRNA). As judged from studies with pure cultures
      of a number of bacterial species, gram-negative and gram-positive organisms were
      lysed equally well by this procedure. The amount of PCR product was proportional
      to the number of cells analyzed over the range tested, 500 to 50,000 cells. On
      the basis of studies with plaque samples that were spiked with known quantities
      of the oral bacterium Treponema denticola, the DNA prepared from plaque was free
      of substances inhibitory to PCR. This method should have utility in molecular
      genetic studies of bacterial populations not only in uncultured plaque samples
      but also in other complex bacterial assemblages.

PMID- 8526529
TI  - Responses to toxicants of an Escherichia coli strain carrying a uspA'::lux
      genetic fusion and an E. coli strain carrying a grpE'::lux fusion are similar.
AB  - A transcriptional fusion of the Escherichia coli uspA promoter to luxCDABE was
      characterized and compared with a heat shock-responsive grpE'::lux fusion.
      Similarities in range and rank order of inducing conditions were observed;
      however, the magnitude of induction was typically greater for the grpE'::lux
      fusion strain.

PMID- 8526530
TI  - Orally administered bovine lactoferrin inhibits bacterial translocation in mice
      fed bovine milk.
AB  - Feeding of bovine milk to mice induced a high incidence of bacterial
      translocation from the intestines to the mesenteric lymph nodes, and the bacteria
      involved were mainly members of the family Enterobacteriaceae. Supplementation of
      the milk diet with bovine lactoferrin or a pepsin-generated hydrolysate of bovine
      lactoferrin resulted in significant suppression of bacterial translocation. Our
      findings suggest that this ability of lactoferrin to inhibit bacterial
      translocation may be due to its suppression of bacterial overgrowth in the guts
      of milk-fed mice.

PMID- 8526531
TI  - Rapid and accurate identification of Escherichia coli K-12 strains.
AB  - A specific PCR for the identification of K-12 strains, based on the genetic
      structure of the O-antigen gene cluster (rfb) of Escherichia coli K-12, is
      described. The assay clearly differentiates E. coli K-12-derived strains from
      other E. coli strains used in the laboratory or isolated from human and animal
      clinical specimens, from food, or from environmental samples. Moreover, lineages
      of K-12 strains can be distinguished with a second PCR based on the same gene
      cluster. The method presents a useful tool in identifying K-12 for monitoring
      strains which are used as biologically safe vehicles in biotechnological
      research, development, and production processes.

PMID- 8526532
TI  - [Renal cystic mass: the diagnostic dilemma].
AB  - OBJECTIVE: To determine the best diagnostic approach and management of cystic
      renal mass. METHODS: Four cases are described and the literature reviewed.
      RESULTS: Of the 4 cases of cystic renal mass, 2 had a previous history of renal
      trauma. Puncture and aspiration of the cystic content were performed in three
      cases; cytology was positive for malignancy in one, which was confirmed by the
      histologic analysis. Two cases underwent nephrectomy although one of the post
      traumatic cases had a preoperative diagnosis of pararenal pseudocyst. The
      literature review showed a significant controversy exists concerning the
      diagnostic approach and treatment. CONCLUSIONS: We advocate an approach free from
      tenets, where all the appropriately chosen diagnostic tools may be valid. If
      doubts persist after diagnostic evaluation, nephrectomy should be performed.

PMID- 8526533
TI  - [Malacoplakia of the prostate and seminal vesicle. Ultrastructural study and
      review of the literature].
AB  - OBJECTIVES: The present study describes a case of malacoplakia of the
      genitourinary tract arising in the seminal vesicle and prostate and reviews
      similar cases previously reported in the literature. METHOD: A 67-year-old male
      consulted for hemospermia and voiding symptoms. Prostatic neoplasm was suspected
      on the basis of the clinical and radiological findings. RESULTS: The diagnosis
      was made only after biopsy and histological analysis. Electron microscopy is a
      very useful tool. Long-term antibiotic therapy may achieve optimal results.
      Treatment with fluoroquinolones was successful. CONCLUSION: To avoid unwarranted
      radical approaches, we underscore the possibility that prostatic pseudotumors may
      be misinterpreted as neoplasia. Malacoplakia is diagnosed only by histology and
      requires medical treatment.

PMID- 8526534
TI  - [Substitutive orthotopic ileocystoplasty. The Studer's technique].
AB  - OBJECTIVES: The results of the Studer enterocystoplasty technique is analyzed,
      with special reference to the early and late complications and urinary
      continence. METHODS: We reviewed the records of 20 patients that underwent
      bladder substitution according to the Studer technique due to bladder carcinoma
      from 1990-1993. Patient follow-up ranged from 6-36 months. The ureteroileal
      anastomosis was done by the single stitch technique onto a tubularized ileal
      chimney. RESULTS: The median age was 57.2 +/- 11.86 yrs (range 33-73). The
      preoperative stay for intestinal preparation ranged from 1-29 days (median 4.4 +/
      5.84) and the postoperative stay ranged from 1-60 days (median 26 +/- 11.44).
      The average operating time was 5.30 +/- 0.7 hours (range 4.15-7). There were two
      postoperative deaths; one from acute myocardial infarction and the other from
      pulmonary embolism. Three patients died from tumor progression during follow-up
      and one from leg ischemia 17 months postoperatively. Early complications: 2 cases
      of prolonged ileus, 1 wound infection, 7 urinary infections, 1 low debit
      intestinal fistula which resolved with parenteral nutrition, 3 patients had
      leakage at the ileourethral anastomosis which resolved with prolonged catheter
      drainage of 3-15 days, 1 hemorrhage from acute lesions to the gastric mucosa, 3
      fascial dehiscence and 1 ureteroileal fistula that required reimplantation into
      the neobladder. Late complications: 1 ureteroileal stenosis that progressed to
      renal atrophy, 1 enterourethral stenosis that resolved with internal urethrotomy
      and 2 cases of severe metabolic acidosis and dehydration that resolved with fluid
      therapy. No differences were observed between the creatinine, pH and ion levels
      preoperatively and during follow-up. Continence was assessed in 17 cases: 100%
      were continent during the day, 41.2% were continent during the night, 4 had
      occasional nocturnal leakage and 6 required collecting devices during the night.
      CONCLUSIONS: The Studer technique provides good results and quality of life to
      patients undergoing cystectomy. Although it carries a high morbidity,
      conservative management will suffice in a high percentage of cases.

PMID- 8526535
TI  - [Calmette-Guerin bacillus in the prophylaxis of superficial bladder tumors. Our
      experience and our doubts].
AB  - OBJECTIVE: This study was conducted to determine the efficacy of our BCG dose and
      schedule for prophylactic therapy in superficial bladder tumors. METHODS:
      Following complete TUR, 81 mg intravesical BCG were administered weekly for six
      weeks and for nightly another six times. The patients were evaluated every three
      months by cytology, cystoscopy and routine analysis. RESULTS: 21/25 patients
      completed the treatment. At 15.5 months median follow-up, 18/21 (85.7%) were
      disease-free, 2/21 (9.5%) had recurrence and 1/21 (4.7%) showed disease
      progression. CONCLUSIONS: BCG is the most effective prophylactic therapy for
      superficial bladder tumors currently available. The ideal dose, treatment
      schedule and its mechanism of action are as yet unknown.

PMID- 8526536
TI  - [Acquired urethral diverticulum in males with spinal cord injury].
AB  - OBJECTIVES: To study the clinical features, etiology, diagnostic methods and
      therapeutic possibilities in male patients with medullary lesion presenting with
      acquired urethral diverticulum. METHODS: A retrospective study was conducted on
      patients seen in our department over the past twenty years (June, 1974 to June,
      1994) for acquired urethral diverticulum. Ten patients have been treated for the
      foregoing condition. RESULTS: The etiology of the medullary lesion was traumatic
      injury in 7 cases and spina bifida in 3 cases. The most frequent cause of the
      acquired urethral diverticulum was a condom-like urinary collecting device
      associated with a septic factor. Three patients presented intradiverticular
      lithiasis. These 3 patients had previous or current lithiasis at other sites of
      the urinary tract and all of them had a condom-like collecting device. All
      patients underwent surgery consisting in diverticulectomy and lithectomy, when
      required. One patient had a recurrence 6 years later because the underlying
      factors causing the diverticulum were still present. CONCLUSIONS: Personal care
      and hygiene of patients with medullary lesion is one of the most important
      factors in preventing urethral injuries. In our view, patient follow-up should
      include regular radiologic assessment and correct training in the use of condom
      like urinary collecting devices and urinary catheters. We advocate one-stage
      surgical repair with temporary cystostomy, preoperative antibiotic therapy
      according to the antibiotic profile and culture of symptomatic and asymptomatic
      urinary infections and the use of methylene blue to ensure the suture is
      watertight.

PMID- 8526537
TI  - [Surgical treatment of male hypospadias with pediculated transversal preputial
      flap technique: a 10-year follow-up].
AB  - OBJECTIVES: The study was conducted to evaluate the long-term follow-up
      micturition data, sexual function and cosmetic results of hypospadias surgical
      repair. METHODS: 14 males (mean age 19.6 yrs) submitted to hypospadias surgical
      repair with the pedicled preputial tubulized flap technique 10 years ago were
      evaluated. RESULTS: The most frequent site of the anomaly was the distal third of
      penis (85.6%). The micturition data were excellent and urinary flow rates were
      normal in 92.8%. Erection and ejaculation were normal in all patients. Penile
      curvature persisted in 14.2%; 64.2% of the patients had sexual intercourse
      (completely satisfactory in 66.6%), penis size was normal in 78.6% and 66.6% of
      the patients were married and had children. No longterm follow-up complications
      were observed. CONCLUSIONS: The technique achieved excellent cosmetic and
      functional results.

PMID- 8526538
TI  - [Technics of ureteral endoscopic access].
AB  - OBJECTIVES: The present article briefly reviews the history of endoscopic access
      to the ureter, since visualization of the ureter was first attempted until the
      procedure was developed by Perez-Castro in 1979. METHODS/RESULTS: The development
      of the rigid ureteroscopes, the difficulties arising from the anatomical
      structures during endoscopy that require ureteral dilatation, the anatomy of the
      juxtavesical segment of the ureter and the pathologies that may alter it, and the
      present and future indications of ureteral dilatation are discussed. Patient
      preoperative evaluation is briefly described and one of the techniques of
      ureteral dilatation is analyzed. Finally, a brief summary comparing the different
      techniques is given. CONCLUSIONS: The technique of choice for ureteral dilatation
      must be simple, easy to perform, low-cost and one which reduces the iatrogenic
      lesions and shortens the duration of hospital stay.

PMID- 8526539
TI  - [Trigono-cervico-prostatotomy (TCP) versus transurethral resection of the
      prostate (TURP). Our experience].
AB  - OBJECTIVE: Trigonocervicoprostatotomy (TCP) has been considered up to now an
      alternative treatment to transurethral resection of the prostate (TURP) when
      evaluating the size of the prostate. This paper demonstrates that endoscopic
      visualization is more important when choosing the surgical procedure and that
      both techniques can achieve satisfactory results. METHODS: The prostate volume is
      evaluated by ultrasound and according to the endoscopic findings, TURP or TCP is
      performed. The prostatic lobes are routinely biopsied if the latter procedure is
      chosen. RESULTS: We compared the results of 34 TCP and 30 TURP procedures using
      the values of I-PSS and uroflowmetry before and after surgery. In 86.2% of the
      TCPs and 80% of the TURPs, the patients are asymptomatic with I-PSS less than 7
      and significantly improved uroflowmetry data. Biopsy disclosed adenocarcinoma in
      one patient submitted to TCP. CONCLUSIONS: TCP represents an alternative to TURP
      not only for small prostates (30 gm) but also for medium-sized prostates (50-60
      gms), depending on the endoscopic findings. TCP is not indicated for lateral
      lobes that fall on the prostate floor. Performing a biopsy routinely in TCP does
      not prolong the operating time significantly and permits detecting subclinical
      adenocarcinoma of the prostate.

PMID- 8526540
TI  - [Transurethral resection of prostate cancer: efficacy and morbidity].
AB  - OBJECTIVES: The efficacy and morbidity of transurethral resection of the prostate
      (TURP) were evaluated in patients with urinary retention and prostatic carcinoma.
      METHODS: From 1990 to 1993, 30 patients with infravesical obstruction secondary
      to prostate cancer were treated by TURP. The results were considered good when
      patients were able to void and were completely continent following the procedure,
      whereas poor results were defined as incontinence or no relief of urethral
      obstruction 21 days following catheter removal. RESULTS: Patient mean age was 72
      years and the average weight of resected tissue ranged from 8 to 105 gms (mean
      19.5 gms). The median postoperative follow-up period was 20.5 months (range 6-36
      months). During this time, there were no deaths and 72.5% of the patients showed
      normal post-TURP micturition. Eight patients (27.5%) developed the following
      complications: 3 were incontinent, 6 had persistent obstruction and 1 patient had
      both complications. Presurgical hormone therapy, high-grade tumors and patient
      age under 70 years appear to be statistically related to poor outcome following
      TURP. CONCLUSIONS: TURP is an effective treatment with a relatively low morbidity
      and offers a viable option for patients with symptomatic urethral obstruction due
      to prostate cancer.

PMID- 8526541
TI  - [Retroperitoneal tumor arising from neural crest: ganglioneuroma+].
AB  - OBJECTIVES: This study shows the contribution of the different imaging methods in
      the diagnosis of retroperitoneal ganglineuroma. METHODS: A retroperitoneal mass
      was incidentally detected in a young male patient. Patient evaluation included
      plain abdominal radiography, intravenous urography, ultrasound and computed
      tomography. RESULTS: Ultrasound and computed tomography provide information on
      tumor characteristics and extent, although it has no diagnostic specifity and
      does not permit distinguishing ganglioneuroma from other neural crest tumors.

PMID- 8526542
TI  - [Renal hydatidosis: importance of preoperative diagnosis].
AB  - OBJECTIVE: We report on a patient who underwent a right nephrectomy for a mass
      suggesting hypernephroma, which was shown to be renal hydatid disease on
      pathological examination. METHODS/RESULTS: The epidemiological, diagnostic and
      therapeutic aspects described in the literature are briefly reviewed.
      CONCLUSIONS: Although uncommon, renal cystic lesions should be suspected in the
      presence of a renal mass and a differential diagnosis should be made. CT is the
      most useful diagnostic imaging technique. The importance of preoperative
      diagnosis for the surgical strategy is underscored.

PMID- 8526543
TI  - [Submucous urethral angioma].
AB  - OBJECTIVES: Urethral hemangioma is a rare benign vascular tumor. The clinical
      features of this tumor type and the therapeutic options are discussed.
      METHODS/RESULTS: We report on a 55-year-old male with urethral hemangioma who
      consulted for urethral hemorrhage. CONCLUSIONS: To our knowledge, approximately
      40 cases of this rare tumor type have been reported in the literature.
      Urethroscopy is the best diagnostic procedure. Treatment depends on tumor site,
      size and number. Transurethral resection of the tumor, urethrectomy, arterial
      embolization, radiotherapy or ablation with Nd:YAG laser can be utilized.

PMID- 8526544
TI  - [Ectopic ureter in prostatic urethra. Unusual discovery in an adult].
AB  - OBJECTIVE: Ectopic ureter is a congenital anomaly more frequent in the female, in
      the pediatric age and is commonly left-sided. The present article reports an
      uncommon case without the common features of this anomaly. METHODS/RESULTS: We
      report on a 67-year-old man with complete duplex system and ectopic obstructive
      megaureter in the prostatic urethra with a silent onset. The diagnostic and
      therapeutic aspects in the literature are briefly discussed. CONCLUSION: Because
      this anomaly is asymptomatic and incidentally discovered because of contralateral
      disease, the approach is conservative.

PMID- 8526545
TI  - [Intravesical foreign body caused arising from ureterostomy protective resin
      gum].
AB  - OBJECTIVES: Bladder foreign bodies can arise from many factors and are iatrogenic
      in a high percentage. A case of intravesical foreign body from accumulated
      fragments of synthetic gum utilized to protect the ureterostomy is described.
      These problems can be avoided by correct management of the osteotomy and must
      therefore be emphasized to those responsible for the patient's care.
      METHODS/RESULTS: A case of a 7-year-old patient with chronic nephropathy and a
      bilateral high-loop ureterostomy is described. The migration and subsequent
      condensation of small fragments of the material protecting the ureterostomy led
      to the formation of a foreign body which took the shape of the bladder. Treatment
      was by vesicostomy. CONCLUSION: The possible complications arising from the
      passage of objects from outside into the urinary tract should always be taken
      into account in patients with an external urinary diversion.

PMID- 8526546
TI  - [Spontaneous bladder rupture with no apparent reason, a peculiar clinical
      occurrence].
AB  - OBJECTIVES: Herein we describe a case of spontaneous rupture of the bladder
      presenting with uncommon clinical features that led to difficulty in making the
      diagnosis. The literature on similar cases in briefly reviewed. METHODS/RESULTS:
      A case of rupture of the bladder arising from no apparent cause is described.
      Oliguria and abdominal pain were the presenting features and analysis disclosed
      renal failure. CONCLUSIONS: Rupture of the bladder may cause acute renal failure
      and acute abdomen and should therefore be included in the diagnostic algorithms
      of both disease entities.

PMID- 8526547
TI  - [Splenic abscess secondary to xanthogranulomatous pyelonephritis].
AB  - OBJECTIVE: We report another case of splenic abscess after nephrectomy, a
      condition which must be considered in the differential diagnosis of post
      operative fever. METHODS/RESULTS: A 20-year-old man presented with lumbar pain
      and fever. A diagnosis of xanthogranulomatous pyelonephritis was made and he was
      treated by subcapsular nephrectomy. Thirty days later the patient presented with
      a lumbar fistula from a splenic abscess and was treated by splenectomy.
      CONCLUSIONS: Fistulas and abscesses are more common after nephrectomy for
      xanthogranulomatous pyelonephritis. In our view, the subcapsular approach is an
      additional risk factor for the foregoing complications.

PMID- 8526548
TI  - Experimental study of ureteral free grafts. I. Surgical findings in transplanted
      and abandoned ureter.
AB  - OBJECTIVE: To develop two experimental models in rats to study the ureter under
      conditions of total devascularization and denervation. METHODS: The ureter was
      autotransplanted as an integrated autologous free graft (IAFG) or abandoned in
      the retroperitoneum as a non integrated autologous free graft (NIAFG). Both
      models were compared with a normal group and a surgical control group. Sixty-two
      rats were randomly distributed: Normal ureter (NU) group (n = 20); surgical
      control, only ureterolysis (SC) group (n = 15); abandoned ureter as NIAFG (AU)
      group (n = 13); reimplanted ureter as IAFG (RU) group (n = 14). RESULTS: SC
      group: in all cases a ureter with no alterations was observed although with
      slight periureteral fibrosis. AU group: some ureter specimens had a smaller
      caliber. Periureteral fibrosis was observed in all the cases. Vessel distribution
      was similar to that of the NU group. All the ureters conserved their lumen. 53.8%
      of the ureters showed spontaneous contractions and 100% contractions after
      mechanical stimulation. Cyst formation, necrosis, fistulas or stenosis of the
      lumen were not observed. RU group: microscopic findings of the ureter segment
      used as IAFG were compatible with those of a normal ureter. In all the cases a
      moderate degree of periureteral fibrosis was observed. In the majority of the
      cases a vascular framework of the fat immediately adjacent to the ureter was
      observed. In 13 of the 14 operated cases spontaneous contractions were observed.
      The ureteral segment used as IAFG showed no alterations in 10 cases and with
      alterations of various types in 4 cases. In 8 cases there was a greater or lesser
      degree of stenosis of the proximal suture. CONCLUSIONS: The surgical findings and
      the macroscopic aspects of the four groups show the viability of the ureter free
      graft, IAFG as well as the NIAFG, in spite of the macroscopic changes.

PMID- 8526549
TI  - Telepathology. 2nd European Conference. Paris-Dijon, 9,11 June 1994. Proceedings.

PMID- 8526550
TI  - Telepathology in France. Justifications and developments.
AB  - Since 1985, the French National Association ADICAP (Association for the promotion
      of computer use in Cytology and Anatomic Pathology) has been active in the
      creation a microscope workstation for developing a bank of digitized images to be
      used for diagnostic and educational purposes. In 1989 one of the authors (P.
      Dusserre) has created a first telepathology network using this workstation. Since
      then, 32 workstations have been set up in private and public Departments of
      Pathology. Two of them are located overseas, in the Martinique and Guadeloupe
      islands. In this paper, the authors describe this system, called Transpath, which
      is a multi-purpose and modulable workstation. 3-years experience and several
      accuracy tests have shown that the quality of transmitted images ensure a
      reliable diagnosis in more than 95% of cases. It has been decided to extend this
      service to other French overseas territories and to develop a group of experts.
      The images bank will also be developed and recorded on CD-ROM. The authors intend
      to participate in a future European project (PILOT project, i.e. Pathology
      International and Local Operational Telematics), with the purpose of establishing
      real intercommunication between European and other networks on a worldwide basis.

PMID- 8526551
TI  - Telepathology in Europe. Its practical use.
AB  - Progress in pathology is related to application of new biological techniques and
      impact of electronic devices affecting transfer of information and images. The
      increase of specification of all kinds of disease classification induces a
      specific need for data exchange and expert consultation. The momentary technical
      situation in communication lines connected with medical fields, especially
      pathology is characterized by parallel operation of two basically different
      communication systems, namely a) systems based upon computerized data exchange (E
      mail, etc.), and b) systems working at public access, i.e. telephone lines and
      their successors (digitized network, satellite system). Practical use in
      telecommunication in pathology has been gathered nearly exclusively by use of the
      second (public) system, and includes intraoperative classification of
      histological images (frozen sections), expert consultations, panel discussions,
      quantitative measurements, and access to image data bank systems. The use of
      remote control microscopes has been reported to work without major errors from
      Norway and Switzerland. In Norway, images and diagnostic informations are
      transferred by use of broad band networks (satellite communication), whereas in
      Switzerland the digitized network ISDN is used. The experiences show clearly that
      remote control microscopes are practicable and reliable tools for daily
      diagnostic work of pathologists, and that the quality of the transferred images
      is sufficient to allow sophisticated diagnoses. Expert consultations are
      routinely performed by use of the common telephone network in lung pathology, and
      can not be underestimated in their impact on the daily work. Accuracy of
      diagnosis, quality of staining and tissue handling, and reliability of diagnosis
      are automatically improved besides the positive legal aspects.

PMID- 8526552
TI  - [Telemedicine and medical responsibility].
AB  - Dealing with telemedicine including telediagnosis and teleassistance, we have to
      assess the legal and ethical components of medical liability. With medical
      telediagnosis, the dispersion of medical liabilities is the main risk: how can we
      ensure a clear identification of the medical liabilities involved in case of
      damage? From a legal point of view, the dispersion of the liabilities is not
      authorized and the use of telediagnosis must ensure a total transparence. As we
      cannot presently establish a separate amount for a medical act based on the cost
      of the image records and the cost of image interpretation, it is necessary to
      establish a contract. Today the most convenient is a contract similar to the
      usual contract between laboratories which implies that the liability belongs to
      the practitioner who has received the sample. In the future, other legal
      obligations may appear when telediagnosis develops. Indeed, the increase in
      reliability due to telediagnosis could be normally required as a part of the
      medical obligation to use the latest technology. On the opposite, the excessive
      use of teleassistance, when there is neither emergency nor medical isolation, is
      dangerous because it affects the integrity and the quality of the medical act. A
      medical practice without any clinical examination of the patient is contrary to
      medical ethics.

PMID- 8526553
TI  - Previous experience in teleradiology could serve as a first lesson to
      telepathologists.
AB  - The author draws the following conclusions from twenty years of experience with
      teleradiology and in telemedicine in general. 1) Standardise now. Use existing
      standards, keep protocols open for other partners. The use of "protected" or
      "slightly" modified standards will not open the market. On the contrary, it will
      slow down developments in telepathology. How many manufacturers are capable of
      exchanging images over normal communication lines (analog or ISDN) with others
      than themselves? 2) Develop adequate user-interfaces. Priority levels should be
      set. The display has to adapted to the user. For pathologists this means using a
      microscope to view the images that have been sent [11]. For radiologists this
      means a dynamic user-interface adapted to the radiologists needs and wishes and
      which provides the best possible working environment [5]. 3) Integration with the
      HIS. The purchase and installation of telemedicine equipment should be integrated
      in a whole informatisation strategy and not be considered as a standalone act.

PMID- 8526554
TI  - Telemicroscopy stations for telepathology based on broadband and ISDN
      connections.
AB  - Telemicroscopy equipment is a key tool to perform Telepathology successfully. It
      allows the local separation of the microscope with the tissue samples from the
      investigating pathologist. The Telemicroscopy stations presented provide the user
      with a full access to the functions such as scanning stage, focus, illumination
      and magnification selection of a remote microscope. One system applies as
      communication link a broadband video conference net of the German Telekom with
      full realtime capabilities and color TV-image quality. As this network provides
      adequate interfaces for video and computer net signals, it is well suited to
      establish within a short time interval a very comfortable Telemicroscopy
      connection without the development of additional equipment. As the broadband
      network is expensive the application is economically restricted to special
      applications. The other system relies on the narrow band connections of the ISDN
      telephone network. This design is inexpensive with respect to data transmission
      and is available nearly worldwide everywhere. But on the other hand this strategy
      is limited concerning realtime capabilities. To reduce these limitations to an
      acceptable level intelligent coding and operation concepts of the stations have
      to be developed.

PMID- 8526555
TI  - Aspects of telepathology in routinary diagnostic work with specific emphasis on
      ISDN.
AB  - Histopathological diagnosis is based upon visual information and additional
      clinical and environmental factors. Information can be transmitted over long
      distances in real time without difficulties. Thus, telecommunication is a
      technique which may be used in pathology. Several approaches have been performed
      to introduce telepathology into the daily work of pathologists. Histopathological
      images of intraoperative sections were transmitted between the Department of
      Pathology, Thoraxklinik, and the Institute of Pathology, Klinikum Baumgartner
      Hohe, Vienna. The transfer time of one image lasted 1-2 minutes depending upon
      the time of the day; i.e. during telephone "rush" hours the transmission time
      increased from 1.1 min to more than 2.4 min. As an average, 2 different sections
      of the image at usually 2 different magnifications were transmitted. Parallel
      discussion of the images, and acoustic assistance in diagnostic classification or
      advice lasted for an additional average 3 min. A substantial assistance in the
      intraoperative classification of the diseases was achieved in 35-40% of cases. No
      breakdown of telephone lines or communication was observed, while this was the
      case for the telepathology trials performed by ISDN between the Department of
      Pathology, Thoraxklinik and the Department of Pathology, Robert Bosch
      Krankenhaus, Stuttgart. These trials included expert consultation of difficult
      paraffin embedded cases of various lung diseases. The transmission time of 1
      image lasted an average 10 sec was the transfer of non average 4-6 images of the
      same case was required for substantial assistance in diagnostic classification.
      The value of the diagnostic assistance was confirmed by submission of the
      corresponding slides to the partner after termination of the telepathology
      conference.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526556
TI  - Pathology consultation services via the Arizona-International Telemedicine
      Network.
AB  - The Arizona-International Telemedicine Network (AITN) links 4 cities in Arizona
      and two international sites in China and Mexico, into a telepathology diagnostic
      network. Established in 1993, the Network provides second opinions on surgical
      pathology and cytopathology cases. Workstations are 486 PC-based computers.
      Static images (1024 x 774 x 8 pixels) are grabbed with a variable resolution
      video camera and sent by 14,400 bit per second modems over ordinary telephone
      lines. Second opinions are either rendered directly by a general telepathologist
      or triaged to a specialist. Experience with the first 37 cases indicates a high
      level of success in providing useful information to referring pathologists over
      the Network.

PMID- 8526557
TI  - To judge the judges--kappa, ROC or what?
AB  - When two raters or two classification methods are compared, it is of interest
      both to describe to which extent they give identical results and to find out
      whether they differ in a systematic way. More often than not, the kappa
      coefficient (K) is used-inspite of well known short comings concerning this
      characteristic and the difficulties to display the results in a digestible way.
      For the comparison of two dichotomous classification methods it will be
      demonstrated that the confidence interval for the systematic difference between
      the methods is related to the kappa coefficient so that the standard error for
      the difference decreases with increasing kappa values. A graphical presentation
      utilizing this fact is proposed. The confidence interval is compared with the
      length had the two methods been completely unrelated and with the length if K had
      the largest possible value, given the actual value of the difference. The
      procedure is extended to the comparison of two methods with ordinal scales and a
      number of comments regarding the comparison between different classification
      methods will be given. Finally, a real life example comparing two pathological
      classification methods is used as a basis for demonstrating a number of different
      ways to display the results from this type of studies by means of elementary
      statistical methods.

PMID- 8526558
TI  - A national telepathology trial in Sweden feasibility and assessment.
AB  - The telepathology trial in Sweden was designed to study several parameters, eg,
      the specific need, practical handling, image quality and acceptance of a static
      imaging system for consultations between pathologists. From September 1992 until
      December 1993, six telepathology systems were leased and temporarily installed
      for 8 to 10 weeks in 29 pathology departments in Swedish hospitals. Three
      telepathology systems were purchased by the university hospitals in Gothenburg,
      Linkoping and Uppsala and served as permanent nodes. To assess the project, pre
      and post field-test questionnaire (focusing on attitudes/expectations and
      experience/wishes for the future, respectively) were sent to all participating
      pathologists and cytologists. Although other assessment methods were included in
      the project, this paper concentrates on the study of questionnaire results. The
      study shows that the major medical requirements for telepathology in Sweden
      involve diagnostic questions concerning: cancers in general, grade of malignancy,
      malignancy of soft tissue, haematopoetic system, skeletal system, breast, uro
      genital systems and applications in the field of dermatology, inflammations and
      transplantations. Telepathology will enhance diagnostic accuracy according to 37%
      of the responding physicians in the pre field-test study and 31% in the post
      field-test study, a drop which may reflect excessively high expectations or less
      than optimal test conditions. A static-image transfer telepathology system was
      used but the assessment clearly shows that pathologists and cytologists prefer a
      dynamic imaging telepathology system for the future. Image resolution is crucial
      and was not adequate for all applications in the study. Half of the respondents
      preferred having a telepathology system in their own departments.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8526559
TI  - Future strategy for telepathology in Sweden: higher resolution, real time
      transmission in a multipurpose work station for diagnostic pathology.
AB  - The general reaction among Swedish pathologists to the nationwide experimentation
      static teletransmission of microscopic images can be briefly summarized as
      follows: "interesting, but technically imperfect: we need more friendly
      interface, faster transmission, preferably in real time, better resolution, and
      the possibility for slide operation by the receiver". In Sweden all Pathology
      laboratories are presently changing administrative routines to PC-platformed
      networks, which means that each pathologist has a microscope and a PC as
      obligatory tools to perform diagnostic work. Therefore, we plan to incorporate
      Telepathology, including picture archiving, along with administrative software
      and improved software for static DNA-measurements and morphometry. The latter is
      including a novel system for quantification of color images e.g.
      immunohistochemistry into a standard work-station for diagnostic pathology. The
      features of this technique are presented as well as the general outline of the
      work-station. Steps have been taken to build up and test such a work-station in
      the broad band (ATM) laboratories of the Ericsson Company and a cooperation with
      several Scandinavian partners in computer and teletechnology. Hopefully, similar
      competitive actions are taken elsewhere to help bring down the prices and
      facilitate adoption among diagnostic pathologists world-wide.

PMID- 8526560
TI  - [Reliability of the anatomopathological diagnosis by static image transfer].
AB  - 50 hepatic biopsies and 50 prostatic biopsies were submitted for diagnostic to an
      expert by the mean of static images previously digitalized by a consulting
      pathologist. Accuracy of diagnosis was obtained in 2 minutes with 4 images in 86%
      of cases. Additional data such as new images, several power fields, permitted
      accuracy of diagnosis in 98% of the cases. The experiences showed clearly that
      the quality of the transferred static images is sufficient to allow diagnoses. It
      pointed out the importance of the different actors involved in the consultation.
      It illustrates the possible use of this system as a training tool.

PMID- 8526561
TI  - How to evaluate the quality in a system of video-microscopy in the field of
      anatomic pathology.
AB  - The acquisition of a video microscope image is explained by the concept of
      modulation transfer function to describe the quality of a microscope which should
      target a sensor of a video camera to allow around 50 pairs of lines per mm with a
      good contrast in the video-monitor. Taking this into consideration, high aperture
      lenses, a microscope with infinity optics, a low power video adapter and a high
      quality camera must be used.

PMID- 8526562
TI  - Remote frozen section service in Norway.
AB  - Remote frozen section service has been in regular use in northern Norway since
      1990. Two local hospitals are equipped with a motorized video microscope remote
      controlled from the workstation at the University Hospital. The video images are
      transmitted via a two ways audio and video telenetwork. This dynamic
      telepathology system utilizes a videocodec for image compression and a transfer
      rate of 384 Kbit/s. The video images of surgical specimens and frozen sections
      are displayed on monitors at both the sender and receiver site. From 1990 until
      1. July 1994 tissue from 100 patients have been examined. Breasts and thyroid
      tissues accounts for 74 of cases. Correct benign versus-malignant diagnosis has
      been given obtained in 89 cases. One false positive, three false negative and
      seven deferred diagnosis regarding malignancy have occurred. The false positive
      diagnosis had no major consequences for the patient. Two of the deferred
      diagnosis turned out to be malignant. The average time taken for examination of
      each frozen section was 12 minutes (range, 3 to 45 min). Our concept of remote
      frozen section service can be recommended for hospitals without a local service
      in surgical pathology.

PMID- 8526563
TI  - Haematological cytology image bank and teletransmission for microscopic
      diagnosis.
AB  - Video recording of microscopic preparations, digitalization and storage,
      transmission by a specialized telephone network are revolutionizing microscopic
      diagnosis procedures. Adjustment of standardization of medical diagnosis, based
      on internationally recognized classifications and their computerized coding are
      fundamental to this process (ADICAP coding system). We are evaluating
      telediagnosis procedure to test their relevance in practical hematology. Taking
      into account clinical and biological informations is necessary to deal with
      difficult cases, in using in addition to microscopic observations, a compromise
      of analytic data which must be rapidly available in a data bank by cross
      references research. In comparison with other pathological applications, the
      sampling problem is specially crucial in hematologic cases, for which it is
      necessary to observe at high resolution a fairly high number of microscopic
      fields, from the peripheral blood and bone marrow smears, in addition to samples
      of histopathologic sections from bone marrow and/or lymph-node. A previous
      teleconsultation of an extensive data bank appears as being one of the best way
      to reduce the procedure of telediagnosis to the only difficult cases, for which
      clear responses cannot be found in the data bank. A link between the access to
      the data bank and the telediagnosis procedures appears to be a fundamental
      approach. Our first experience shown us that a mean of 10 to 15 observed fields
      are necessary to conclude in ordinary cases (i.e. peripheral blood of
      lymphoproliferative disorders), while up to 30 fields or more are sometimes
      necessary for complex cases (acute leukemias, myelodysplastic and
      myeloproliferative syndromes), including cytologic and histopathologic data from
      the peripheral blood, bone marrow, lymph nodes.

PMID- 8526564
TI  - [Telecytoconsultation: application of the TRANSPATH system to the cervicovaginal
      pathology].
AB  - Telediagnosis in Cytology is possible and useful. As for histology it requires
      education to use this new tool and a new method to make a diagnosis, but also a
      rigorous behaviour. But for cytology, technical restrictions are more important:
      selection of adequate fields, magnification (a 60 x objective is necessary),
      illumination (specially for little round cells, in fact spheric ones), and a good
      knowledge of cytology of both partners to be used with accuracy. This method
      offers no real access to smear's background and false negatives are impossible to
      exclude. Moreover it is difficult to differentiate between endocervical and
      endometrial cells and competence in cytology is much more necessary than for
      histology. A more detailed evaluation is therefore required.

PMID- 8526565
TI  - Experience with distant pathology demonstrations for clinicians in hospitals
      without local pathologists through the Swedish telepathology work station.
AB  - Conferences between pathologists and clinicians are routinely important at each
      hospital which has its own department of pathology. With the aid of
      telepathology, such conferences can be facilitated to provide results similar to
      those in hospitals with their own pathological service. Our Department serves the
      hospital in Motala, which is located 50 km west of Linkoping. We now have
      telepathology conferences every second week with the surgeons and every second
      week with colleagues in internal medicine. The equipment we use is LabEye, which
      is produced by Innovativ Vision AB in Linkoping. This equipment includes mouse
      pointers at both stations which are always visible in the images at both ends of
      the system. The quality of images received in Motala is very good, allowing
      discussion of details regarding the specimens, especially the cytological ones.
      Our experiences with these conferences have been very good.

PMID- 8526566
TI  - A contribution to the quantitative analysis of transmitted images.
AB  - The scope of this paper is to contribute to the analysis of the problem of
      connecting two, relatively distinct, mostly technological, aspects of modern
      pathology. The authors analyze the differences between the values of morphometric
      and other parameters, such as: area, density, perimeter, etc. obtained on the
      same set of images before and after transmission. The results obtained prove that
      the differences due to the compression-transmission-decompression module, which
      is inherent to the image transmission process, are negligible.

PMID- 8526567
TI  - The design and use of a computer-based digital image acquisition, management, and
      communications system for conferencing in pathology.
AB  - The Roche ImageManager is a PC computer-based system, running under Windows 3.1.
      This system allows the storage, viewing, printing, and transmission of, and
      conferencing on large sets of high resolution, color images from various sources.
      Images may be acquired at resolutions up to 3072 x 2320 pixels under software
      control, and transmitted for conferencing or stored in the database using JPEG
      compression. Each image is stored with associated information, text notes,
      annotations, and a "thumbnail" image. The stored information may be searched for
      matching images, for example representative images of a particular disease for
      training, or images to be reviewed for a particular patient. Images may be
      transmitted with all associated information between sites which have telephone
      service, worldwide. Support is being added for LAN use with a multi-user
      database, ISDN and Switch56 communications, and remote microscope control.
      Interactive conferencing allows rapid transmission of low resolution images for
      specimen scanning, viewing of multiple high resolution still images, and real
      time interactive pointers for detailed discussions of image features. The
      ImageManager is being used and evaluated for conferencing and training purposes.
      A study was performed by Roche Biomedical Laboratories to compare the ability of
      pathologists to make a diagnosis on complex cases using transmitted images vs.
      routine microscopic examination. The effectiveness of the system in providing
      images of a sufficient quality to allow diagnosis in a private practice setting
      will be presented.

PMID- 8526568
TI  - Supporting telemicroscopy and laboratory medicine activities. The Greek
      "TELE.INFO.MED.LAB" project.
AB  - In this paper the authors present the basic results of the study for the
      "TELE.INFO.MED.LAB" project. This study is based on the local experience of the
      Metaxas Cancer Institute case and on international references. The possibilities
      rendered by current developments in telemedicine and particularly in
      telepathology accelerate and facilitate the communication of crucial medical data
      and creation of "second level" medical services overcoming the geographical
      particularities of the country. The availability of data transmission (signals,
      images, texts, etc.) enables the creation of a "uniform market" for various
      services. This system must take into account the financial realities,
      geographical aspects transportation problems and technological developments.
      Organization of this system, the choices of technical standards and the
      realization of a complete pilot project are described. For this system we also
      describe the functional and technical aspects, as well as software and hardware
      components for the different types of units.

PMID- 8526569
TI  - Concept of telepathology in Croatia.
AB  - The authors proposed a hierarchically organized telepathology system in Croatia
      connecting smaller hospitals with a single pathologist to three regional centers
      and connecting these regional centers to the National center in Zagreb. The
      national center in Zagreb should later be connected further with all highly
      specialised pathological units in Zagreb and with international centers. This
      will offer broad possibilities of pathological consultations which is the primary
      aim of this system. Further, clave cooperation with other participants in
      telemedicine should be developed, as well as investigation on image analysing of
      transmitted pictures.

PMID- 8526570
TI  - Telemedicine project in the Azores Islands.
AB  - Telemedicine projects and programmes began in Portugal only in 1992 with a
      telepathology programme in real time frozen section service. The main purpose and
      challenge of the telemedicine is to allow the access of a special and specific
      health care to populations as the 250,000 inhabitants of the Azores archipelago.
      We wish to start with telepathology, teledermatology, telecardiology, tele ORL,
      telepsychiatry, telematernal and foetal medicine in all islands of the
      archipelago, also connected with the Major University Centers in Lisbon. The
      system must be composed of a video conferencing station working in ISDN at 384
      kb/sec connectors via a switch to the video camera applied to different video
      cameras. Telemedicine improves the human, economical, social and cultural life
      quality to the people of the European, but depressed ultraperipherical region of
      Azores.

PMID- 8526571
TI  - Quantitative DNA analysis: a comparison of conventional DNA ploidy analysis and
      teleploidy.
AB  - JPEG compression can be used on images for DNA ploidy analysis if careful
      consideration is given to the level of compression used for file storage. The
      amount of JPEG compression possible may vary depending on the type of tissue
      analyzed, however, a compromise may be reached for all types of tissue. JPEG
      compression should not go over a level of 70 for DNA analysis as this would
      result in possibly erroneous IOD calculation and erroneous DNA ploidy analysis.
      Also, the resulting file quality is so poor that even visual analysis is not
      possible. With careful training of personnel in cell selection, remote DNA ploidy
      analysis would be an effective tool for standardization and quality control in
      the pathology laboratory. By using remote DNA ploidy analysis, it is possible for
      hospitals to consolidate their workload, and make DNA ploidy analysis by image
      cytometry a cost effective test in the laboratory. Proficiency testing would also
      become possible as all laboratories performing DNA ploidy analysis would receive
      the same fields of view for testing. DNA ploidy analysis by image cytometry using
      stored images could be a versatile tool for the telepathology community.

PMID- 8526572
TI  - Multimedic system for telepathology and interdisciplinary councils between
      doctors and various hospitals.
AB  - At present, the exchange of information between clinicians and pathologists are
      limited to mail, telefax and telephone. The bi-directional video communication
      using at least two digitized phone lines (ISDN) is an additional medium for video
      conference and for image exchange. The MECOM system (Medical Communication) has
      been set up in the department of pathology of Aixla-Chapelle Hospital (Germany)
      and has routinely used for two years between 4 local hospitals. Now it is mainly
      used for staff discussions between pathologists and practitioners involved in
      different oncological fields. Mecom can transmit any kind of high resolution
      images (x rays films, scanner images, histologic slides...) which are useful or
      necessary during medical staff discussions. This system requires only two phone
      lines to be operative. However it can turn on up to twelve parallel ISDN lines
      which allow to transmit 768 kbytes/sec. It manages the SG3, HVQ and H320
      compression algorithms and allows the transmission of still images at a
      resolution varying from 256/240 to 512/480 pixels. Mecom is a modulable system
      which adapts to the needs. It has the following advantages. Emergency inter
      disciplinary conferences. Real time images, discussion between a pathologist and
      an expert to confirm histo-pathological diagnosis. Abolition of distances. That
      is specially useful or necessary in countries with low medical population and
      poor transportation network.

PMID- 8526573
TI  - [VISIOPATH: system of telediagnosis and digital image processing].
AB  - VISIOPATH is a system that exploits the most recent techniques for digital
      processing of images. With performance tools, it can acquire and visualise images
      in 16 million colors on a high resolution screen. VISIOPATH has telediagnosis
      functions. It allows an exchange of medical images between doctors in real time
      or recorded. The "Digital Network with Integrated Services" (ISDN), from France
      Telecom which bring a way of communicating that is flexible and efficient, and
      allows an exchange of images, sound and data, with high quality and security. It
      brings to the specialists the means of a stricter interpretation, that is to say
      of a quicker and safer diagnosis. It can be adapted to other medical specialties.

PMID- 8526574
TI  - Tumor angiogenesis. The future is now.

PMID- 8526575
TI  - Tumor angiogenesis as a predictor of recurrence and survival in patients with
      node-negative colon cancer.
AB  - OBJECTIVE: The authors' objective was to quantitatively assess angiogenesis or
      neovascularity within node-negative colon cancers and to determine if increased
      angiogenesis correlated with higher recurrence and lower survival rates. SUMMARY
      BACKGROUND DATA: Neovascularization promotes rapid tumor growth by facilitating
      nutrient and metabolite exchange. Recent work with breast and nonsmall cell lung
      cancers has shown that low angiogenic activity imparts a lower risk of recurrence
      and metastasis. Although adjuvant therapy is beneficial for patients with node
      positive colon cancers, no such benefit has been demonstrated for patients with
      node-negative lesions. Nevertheless, up to 30% of this latter group will
      experience recurrence. We sought to identify a subset of patients with node
      negative colon cancers at high risk for recurrence who might benefit from such
      therapy. METHODS: One hundred five node-negative colon cancers were immunostained
      for endothelial cell factor VIII-related antigen. Blood vessels within three
      microscopic fields at 100X magnification were counted, the mean calculated, and
      an angiogenesis score assigned. A subjective angiogenesis grade (1-4) was
      assigned after each slide was surveyed in its entirety. Score and grade were then
      assessed with respect to cancer recurrence and patient survival. RESULTS: Mean
      patient age was 71 years (range, 41-90 years) and mean tumor size, 5.6 cm (range,
      2-12 cm). Mean follow-up was 6.5 years; mean angiogenesis score, 27.9 (range, 4
      50); and mean grade, 2.0 (range, 1-4). Patients living 5 years had significantly
      lower angiogenesis scores than did nonsurvivors (22.8 vs. 43.2, p = 0.0004). Each
      10-vessel increase in score imparted a 2.0-fold greater hazard of death and a 2.7
      fold greater hazard of recurrence. The probability of surviving 5 years is
      estimated by: [formula: see text] and the probability of recurrence is estimated
      by: [formula: see text] CONCLUSIONS: Angiogenesis within colon cancer is an
      important predictor of tumor behavior and may identify patients at higher risk
      for recurrence and early death.

PMID- 8526576
TI  - Post-treatment management options for patients with lung cancer.
AB  - OBJECTIVES: The first objective was to identify variations in patient management
      practice patterns after potentially curative lung cancer surgery. Patient
      management practice patterns were expected to range from intensive follow-up to
      no active surveillance. The second objective was to measure whether intensity of
      follow-up was related to patient outcomes. METHODS: An 18-month retrospective
      analysis was conducted of 182 patients with low TNM stage (< or = IIIA) lung
      cancer who were surgically treated with curative intent over the 11-year period
      from 1982 through 1992 at the St. Louis Department of Veterans Affairs Medical
      Center. RESULTS: Patients were followed for a mean of 3.3 years, until death or
      the end of the study. Analyses of diagnostic test and outpatient visit frequency
      distributions and cluster analyses facilitated the identification of 62
      nonintensively followed patients and 120 intensively followed patients. Both
      groups were comparable at baseline, and there were no significant differences in
      patient outcomes attributable to intensity of follow-up. Intensively followed
      patients did, however, live an average of 192 days longer than nonintensively
      followed patients. CONCLUSIONS: Significant variations in follow-up practice
      patterns can exist within a single health care facility. In this analysis,
      variations in test and visit frequency did not result in statistically
      significant differences in patient outcomes, though the survival difference
      between groups suggests that some benefit might exist. Only well-designed
      prospective trials are likely to answer the question of what constitutes optimal
      follow-up after potentially curative lung cancer treatment.

PMID- 8526577
TI  - Intraportal endovascular ultrasonography in the diagnosis of portal vein invasion
      by pancreatobiliary carcinoma.
AB  - OBJECTIVE: The purpose of this study was to determine the value of intraportal
      endovascular ultrasonography (IPEUS) in the diagnosis of portal vein invasion by
      pancreatobiliary carcinoma. The authors reported their experiences with this new
      technique and compared it with conventional imaging technologies, such as
      portography and computed tomography (CT). SUMMARY BACKGROUND DATA:
      Pancreatobiliary carcinoma often invades the portal vein. Observation of the
      echogenic band of the portal vein wall by means of a high-frequency, high
      resolution intravascular ultrasound catheter allows for the accurate diagnosis of
      the portal vein invasion. METHODS: A prospective study of 30 consecutive patients
      with pancreatobiliary carcinoma (16 pancreatic carcinomas, 8 bile duct carcinomas
      and 6 gallbladder carcinomas) was performed. In 23 cases IPEUS was performed
      intraoperatively from the superior mesenteric venous route with an 8 French, 20
      MHz intravascular ultrasound catheter. In 7 cases IPEUS was performed before
      surgery from the percutaneous transhepatic route with a 6 French, 20 MHz
      intravascular ultrasound catheter. The finding of IPEUS was confirmed by
      pathologic examination of resected specimens and surgical exploration. The
      results of IPEUS were compared to those of portography and CT. RESULTS:
      Intraportal endovascular ultrasonography visualized the portal vein wall as an
      echogenic band with a thickness of 0.5 mm to 1.0 mm. The diagnostic criterion of
      portal vein invasion was destruction of this echogenic band. Portal vein invasion
      was found in 15 of 30 cases. Vascular invasion was confirmed by pathologic
      examination of resected specimens in 10 patients and operative findings in 5. The
      sensitivity, specificity, and overall accuracy of IPEUS for diagnosis of portal
      vein invasion was 100%, 93.3%, and 96.7%, respectively. The values were 80%,
      67.7%, and 73.3% for portography and 53.3%, 80%, and 66.7%, respectively, for CT.
      CONCLUSIONS: Intraportal endovascular ultrasonography provided precise
      information about the relationship between the pancreatobiliary tumor and the
      portal vein wall. It was capable of accurately detecting or excluding early
      invasion of the portal vein wall by pancreatobiliary carcinoma.

PMID- 8526578
TI  - Shouldice inguinal hernia repair in the male adult: the gold standard? A
      multicenter controlled trial in 1578 patients.
AB  - BACKGROUND: Hernia repair is the second most frequently performed operation in
      France and in the United States, the prevalence being 36 for every 1000 males.
      Lowering the recurrence rate by 1% would mean 1000 fewer operations for hernia
      repair per year in France. METHODS: Between 1983 and 1989, 1578 adult males with
      a total of 1706 nonrecurrent inguinal hernias were prospectively and randomly
      allotted to undergo either a Bassini's repair, Cooper's ligament, or Shouldice
      repair with polypropylene or a Shouldice repair with stainless steel for
      determination of which technique was associated with the lowest recurrence rate.
      Fifty-nine hernia repairs were withdrawn after inclusion. Of the 1647 remaining
      hernias, 52.2% were indirect, 25.6% were direct, and 23.2% were combined.
      Patients were seen every 6 months for 3 years and then every year. Median follow
      up was 5 years 8 months (range, 3 months-8.5 years). RESULTS: At 8.5 years, 5.6%
      of hernias were lost to follow-up. Ninety-seven hernia repairs failed, 50% during
      the first 2 years. The actuarial recurrence rate was 7.94% at 8.5 years. The
      Shouldice repair (stainless steel or polypropylene) was associated with fewer
      recurrences (6.1%) than either the Bassini's (8.6%) or Cooper's ligament repair
      (11.2%) technique (p < 0.001). This difference remained significant even when the
      maximal bias test was used. Fewer recurrences (5.9%) were observed with the
      stainless steel wire Shouldice repair than with polypropylene version (6.5%), but
      the difference was not significant. CONCLUSIONS: Shouldice hernia repair provides
      the patient with the best chances of nonrecurrence regardless of the anatomical
      type of hernia. The Shouldice hernia repair should be the gold standard for
      inguinal hernia repair in men and serves as the basis for comparison with all
      other techniques, be they prosthetic or laparoscopic.

PMID- 8526579
TI  - Preoperative gastric emptying. Effects of anxiety and oral carbohydrate
      administration.
AB  - BACKGROUND: Overnight fasting is routine before elective surgery. This may not be
      the optimal way to prepare for surgical stress, however, because intravenous
      carbohydrate supplementation instead of fasting has recently been shown to reduce
      postoperative insulin resistance. In the current study, gastric emptying of a
      carbohydrate-rich drink was investigated before elective surgery and in a control
      situation. METHODS: Twelve patients scheduled for elective surgery were randomly
      given 400 mL of either a carbohydrate-rich drink (285 mOsm/kg, 12.0%
      carbohydrates, n = 6) or water 4 hours before being anesthetized. Gastric
      emptying was measured (gamma camera, 99Tcm). Each patient repeated the protocol
      postoperatively as a control. All values were presented as the mean +/- SEM by
      means of a nonparametric statistical evaluation. RESULTS: Despite the increased
      anxiety experienced by patients before surgery (p < 0.005), gastric emptying did
      not differ between the experimental and control situations. Initially, water
      emptied more rapidly than carbohydrate. However, after 90 minutes, the stomach
      was emptied regardless of the solution administered (3.2 +/- 1.1% [mean +/- SEM]
      remaining in the stomach in the carbohydrate group versus 2.3 +/- 1.2% remaining
      in the stomach in the water group). CONCLUSIONS: Preoperative anxiety does not
      prolong gastric emptying. The stomach had been emptied 90 minutes after ingestion
      of both the carbohydrate-rick drink and water, thereby indicating the possibility
      of allowing an intake of iso-osmolar carbohydrate-rich fluids before surgery.

PMID- 8526580
TI  - The Objective Structured Clinical Examination. The new gold standard for
      evaluating postgraduate clinical performance.
AB  - OBJECTIVE: The authors determine the reliability, validity, and usefulness of the
      Objective Structured Clinical Examination (OSCE) in the evaluation of surgical
      residents. SUMMARY BACKGROUND DATA: Interest is increasing in using the OSCE as a
      measurement of clinical competence and as a certification tool. However, concerns
      exist about the reliability, feasibility, and cost of the OSCE. Experience with
      the OSCE in postgraduate training programs is limited. METHODS: A comprehensive
      38-station OSCE was administered to 56 surgical residents. Residents were grouped
      into three levels of training; interns, junior residents, and senior residents.
      The reliability of the examination was assessed by coefficient alpha; its
      validity, by the construct of experience. Differences between training levels and
      in performance on the various OSCE problems were determined by a three-way
      analysis of variance with two repeated measures and the Student-Newman-Keuls post
      hoc test. Pearson correlations were used to determine the relationship between
      OSCE and American Board of Surgery In-Training Examination (ABSITE) scores.
      RESULTS: The reliability of the OSCE was very high (0.91). Performance varied
      significantly according to level of training (postgraduate year; p < 0.0001).
      Senior residents performed best, and interns performed worst. The OSCE problems
      differed significantly in difficulty (p , 0.0001). Overall scores were poor.
      Important and specific performance deficits were identified at all levels of
      training. The ABSITE clinical scores, unlike the basic science scores, correlated
      modestly with the OSCE scores when level of training was held constant.
      CONCLUSION: The OSCE is a highly reliable and valid clinical examination that
      provides unique information about the performance of individual residents and the
      quality of postgraduate training programs.

PMID- 8526581
TI  - Comparative assessment of cultured skin substitutes and native skin autograft for
      treatment of full-thickness burns.
AB  - OBJECTIVE: Comparison of cultured skin substitutes (CSSs) and split-thickness
      autograft (STAG) was performed to assess whether the requirement for autologous
      skin grafts may be reduced in the treatment of massive burns. SUMMARY BACKGROUND
      DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan
      substrates populated with autologous fibroblasts and keratinocytes have been
      demonstrated to close full-thickness skin wounds in athymic mice and to express
      normal skin antigens after closure of excised wounds in burn patients. METHODS:
      Data were collected from 17 patients between days 2 and 14 to determine incidence
      of exudate, incidence of regrafting, coloration, keratinization, and percentage
      of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 =
      worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10)
      and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface
      roughness, skin suppleness, and raised scar. RESULTS: Sites treated with CSSs had
      increased incidence of exudate (p = 0.06) and decreased percentage of engraftment
      (p < 0.05) compared with STAG. Outcome parameters during the first year showed no
      differences in erythema, blistering, or suppleness. Pigmentation was greater,
      scar was less raised, but regrafting was more frequent in CSS sites than STAG. No
      differences in qualitative outcomes were found after 1 year, and antibodies to
      bovine collagen were not detected in patient sera. CONCLUSIONS: These results
      suggest that outcome of engrafted CSSs is not different from STAG and that
      increased incidence of regrafting is related to decreased percentage of initial
      engraftment. Increased rates of engraftment of CSSs may lead to improved outcome
      for closure of burn wounds, allow greater availability of materials for grafting,
      and reduce requirements for donor skin autograft.

PMID- 8526582
TI  - Noncausal relationship between cancer recurrence and perioperative blood
      transfusions.

PMID- 8526583
TI  - Hepatolithiasis.

PMID- 8526584
TI  - Peritoneal carcinomatosis.

PMID- 8526585
TI  - Laparoscopic omental patch repair for perforated peptic ulcer.

PMID- 8526586
TI  - Minimally invasive technique for cholecystectomy.

PMID- 8526587
TI  - Cholecystectomy via an epigastric minilaparotomy.

PMID- 8526588
TI  - Appendicular adenocarcinoma.

PMID- 8526589
TI  - Recurrent thyroid cancer.

PMID- 8526590
TI  - Prostaglandin E1 treatment.

PMID- 8526591
TI  - Perforated pyloroduodenal ulcers.

PMID- 8526592
TI  - Surgical management of Meckel's diverticulum.

PMID- 8526593
TI  - Tetralogy of Fallot [S,D,I]: a recently discovered malformation and its surgical
      management.

PMID- 8526594
TI  - Use and misuse of the ejection fraction.

PMID- 8526595
TI  - Disparate effects of nitric oxide on lung ischemia-reperfusion injury.
AB  - BACKGROUND: Inhaled nitric oxide (.NO) has been found to be a potent pulmonary
      vasodilator. We assessed whether .NO, through this function or others, could
      alleviate lung reperfusion injury. METHODS: Rats underwent thoracotomy, with
      clamps used to create left lung ischemia. After 90 minutes of ischemia, clamps
      were released, permitting reperfusion for either 30 minutes or 4 hours.
      Additional animals received inhaled .NO via the ventilator to determine its
      effects on reperfusion injury. RESULTS: Lung injury, measured by increased
      vascular permeability using iodine-125-labeled bovine serum albumin leakage, was
      significantly increased in ischemic-reperfused animals compared with time-matched
      shams not undergoing ischemia. Inhaled .NO delivered at the start of reperfusion
      worsened injury at 30 minutes but was protective at 4 hours. The increased injury
      could be avoided either by delaying .NO for 10 minutes or by treating the animals
      with superoxide dismutase before reperfusion. .NO reversed postischemic pulmonary
      hypoperfusion at 4 hours, as measured by labeled microspheres. Lung neutrophil
      content was significantly reduced at 4 hours in .NO-treated animals. CONCLUSIONS:
      .NO is toxic early in reperfusion, due to its interaction with superoxide, but is
      protective at 4 hours of reperfusion, due to reversal of postischemic lung
      hypoperfusion and reduction of lung neutrophil sequestration.

PMID- 8526596
TI  - The "physio-ring": an advanced concept in mitral valve annuloplasty.
AB  - BACKGROUND: A new annuloplasty ring has been developed with the aim of adding
      flexibility to the remodeling annuloplasty concept. Here we report its clinical
      use with special emphasis on segmental valve analysis and valve sizing. METHODS:
      From October 1992 through June 1994, 137 patients aged 4 to 76 years (mean age,
      49.1 years) were operated on. The main causes of mitral valve insufficiency were
      degenerative, 90; bacterial endocarditis, 15; and rheumatic, 13. The indication
      for operation was based on the severity of the mitral valve insufficiency (90
      patients were in grade III or IV) rather than on functional class (60 patients
      were in class III or IV). At echocardiography 6 patients had normal leaflet
      motion (type I), 119 leaflet prolapse (type II), and 12 restricted leaflet motion
      (type III). Surgical repair was carried out using Carpentier techniques of valve
      reconstruction. In 3 patients, inadequate ring sizing was responsible for
      systolic anterior motion of the anterior leaflet diagnosed by intraoperative
      echo. The valve was replaced in 2 patients. There were three hospital deaths, no
      late deaths, one reoperation for recurrent mitral valve insufficiency due to
      chordal rupture 1 month after repair, one reoperation for atrial thrombus
      formation 5 months after repair, one anticoagulant-related hemorrhage, and one
      thromboembolic episode. RESULTS: Mid-term follow-up between 6 and 18 months was
      available in 94 patients. Echocardiography showed trivial or no regurgitation in
      93.2% of the patients and minimal regurgitation in 6.8%. The average transmitral
      diastolic gradient was 3.55 +/- 1.93 mm Hg. Left ventricular end-systolic
      diameter and volume decreased postoperatively, demonstrating an improved left
      ventricular function. CONCLUSIONS: This preliminary experience has provided
      promising results and allowed us to define the indications of the Physio-Ring
      versus the classic ring. It has also shown that valve sizing and proper ring
      selection are of primary importance.

PMID- 8526597
TI  - Effect of L-arginine cardioplegia on recovery of neonatal lamb hearts after 2
      hours of cold ischemia.
AB  - BACKGROUND: Despite hypothermia and cardioplegia, myocardial ischemia followed by
      reperfusion results in both ventricular and endothelial dysfunction. The
      endothelial dysfunction is characterized by a reduced response to acetylcholine,
      which implies a reduced ability of the endothelium to release nitric oxide after
      hypothermic ischemia and reperfusion. We have previously demonstrated that
      infusion of the nitric oxide precursor L-arginine only during reperfusion after
      hypothermic ischemia significantly improves the recovery of ventricular function
      and results in an increased vasodilator response to the infusion of
      acetylcholine. In contrast, other investigators have found that nitric oxide has
      deleterious effects during postischemic reperfusion. METHODS: In the current
      experiments we have further examined the role of endothelial production of nitric
      oxide by adding 10 mmol/L L-arginine to cardioplegia in isolated, blood-perfused
      neonatal lamb hearts having 2 hours of cold cardioplegic ischemia. In another
      group 10 mmol/L D-arginine, an inactive enantiomer of L-arginine, was added to
      the cardioplegia. Controls received only cardioplegia (dextrose-potassium).
      RESULTS: At 30 minutes of reperfusion, the L-arginine group showed a
      significantly improved recovery in left ventricular systolic function (maximum
      developed pressure, developed pressure at a constant balloon volume [V10]
      resulting in an end-diastolic pressure of 10 mm Hg before ischemia, positive
      maximum dP/dt, and dP/dt at V10), diastolic function (negative maximum dP/dt and
      end-diastolic pressure at V10), coronary blood flow, endothelial function
      (assessed by the coronary vascular resistance response to acetylcholine), and
      myocardial oxygen consumption compared with the control group (p < 0.05). There
      were no significant differences in the recovery of any variables between the D
      arginine and control groups. CONCLUSIONS: These results suggest that provision of
      more substrate for the endothelial production of nitric oxide during ischemia has
      an important salutary effect on the recovery of postischemic myocardial and
      endothelial function and provide further evidence for an important role for the
      endothelial production of nitric oxide in the response to hypothermic ischemia
      and reperfusion in the neonatal lamb heart.

PMID- 8526598
TI  - Predicting survival after coronary revascularization for ischemic cardiomyopathy.
AB  - BACKGROUND: The success of coronary revascularization for ischemic cardiomyopathy
      (left ventricular ejection fraction of 0.25 or less) has been unpredictable. We
      and others have demonstrated that the hospital operative mortality rate for these
      operations has been surprisingly low, particularly if evidence of ischemia is
      present. We subsequently liberalized our selection criteria based on our
      hypothesis that coronary artery bypass grafting is safe in this subset of
      patients regardless of the status of their distal coronary vasculature. METHODS:
      To examine this hypothesis, we studied retrospectively our patients undergoing
      coronary artery bypass grafting from 1983 to 1993. Ninety-six patients with
      ejection fractions of 0.25 or lower underwent this operation, with 88 hospital
      survivors (mortality 8%). All of the patients had clinical symptoms of heart
      failure. The male to female ratio was 4.6:1. The average age was 63.1 +/- 0.9
      years (mean +/- standard error of the mean). Patients were excluded if they had
      valvular heart disease other than mild to moderate mitral regurgitation, required
      resection of a ventricular aneurysm, or required an emergency operation for acute
      coronary occlusion. Possible predictors of death were examined retrospectively.
      The catheterization films were reviewed retrospectively by a cardiovascular
      surgeon who was blinded to patient outcome and was never involved in the clinical
      management of any of the patients. Vessel quality was described as good, fair, or
      poor. RESULTS: Increased age and poor vessel quality were the only significant
      predictors of poor outcome. Sex, presence or absence of angina, preoperative
      angina, preoperative ejection fraction, preoperative arrhythmia disorder, aortic
      cross-clamp time, and the number of bypass grafts had no significant effect on
      outcome in the perioperative period. CONCLUSION: These results demonstrate that
      poor vessel quality and older age are predictors of poor outcome in patients with
      low ejection fractions undergoing myocardial revascularization. We conclude that
      poor distal coronary vasculature is a contraindication to coronary artery bypass
      grafting in patients with an ejection fraction of 0.25 or less, even if angina is
      present.

PMID- 8526599
TI  - Comparing two strategies of cardiopulmonary bypass cooling on jugular venous
      oxygen saturation in neonates and infants.
AB  - BACKGROUND: Cerebral protection during deep hypothermic circulatory arrest is
      predicted on efficient and complete cerebral cooling. Institutions approach
      cooling quite differently. We compared two different cooling strategies in terms
      of measured jugular venous bulb saturations in 39 infants undergoing deep
      hypothermic cardiopulmonary bypass to evaluate the effect of institutional
      cooling practices on jugular venous bulb saturation, an indirect measure of
      cerebral cooling efficiency. METHODS: The patients were grouped based on the
      method of core cooling. In group A (n = 17), core cooling was achieved rapidly by
      setting the water bath temperature of the heat exchanger at 4 degrees to 5
      degrees C, and the patient was cooled until rectal temperature and nasopharyngeal
      temperature were 15 degrees C or lower. In group B (n = 22), the heat exchanger
      was initially set at 18 degrees C and slowly lowered to 12 degrees C. Hypothermic
      temperatures of 12 degrees C were maintained until the nasopharyngeal temperature
      was 18 degrees C or less and the rectal temperature was 20 degrees C or lower.
      Once cooling was complete, blood samples were analyzed by cooximetry for
      determination of arterial oxygen saturation and jugular venous bulb saturation.
      RESULTS: In group A, the measured jugular venous bulb saturation was 98.0% +/-
      0.9% and the oxygen saturation to jugular venous bulb saturation difference was
      0.3% +/- 0.5%, measured at the time that institutional cooling objectives were
      achieved (total cooling time, 15.0 +/- 0.45 minutes). In group B, jugular venous
      bulb saturation was 86.2% +/- 12% and the oxygen saturation to jugular venous
      bulb saturation difference was 10.8% +/- 12.2%, measured at the time that
      institutional cooling objectives were achieved (total cooling time, 17.5 +/- 1.1
      minutes (p < 0.01). CONCLUSIONS: Differences in cardiopulmonary bypass cooling
      techniques may alter the rate at which jugular bulb saturations rise. We believe
      this represents an indirect measure of the efficiency of brain cooling and
      therefore of cerebral protection.

PMID- 8526600
TI  - Antegrade and retrograde continuous warm blood cardioplegia: a 31P magnetic
      resonance study.
AB  - BACKGROUND: Retrograde normothermic blood cardioplegia has been shown to provide
      myocardial protection during certain bypass procedures. However, a number of
      animal studies have shown less than optimal myocardial protection with this
      technique. METHODS: Isolated, beating porcine hearts were perfused antegradely
      (aortic root pressure = 75 to 95 mm Hg) for 30 minutes. Arrest was induced and
      maintained for 60 minutes with high K+ blood cardioplegia delivered either
      antegradely (n = 8) or retrogradely (n = 8) (coronary sinus pressure = 35 to 55
      mm Hg). Perfusate was switched to normokalemic blood for recovery of sinus rhythm
      (30 minutes). Intracellular pH, creatine phosphate, inorganic phosphate, and
      adenosine triphosphate were monitored continuously and noninvasively with
      phosphorus 31 magnetic resonance spectroscopy throughout the experiment, and
      functional variables (rate-pressure product and the positive and negative first
      derivatives of left ventricular pressure) were assessed concurrently. RESULTS:
      Antegrade cardioplegia maintained high-energy metabolites, intracellular pH, and
      myocardial function. Retrograde normothermic blood cardioplegia resulted in an
      increase in inorganic phosphate (197% +/- 15% of control) and a decrease in
      creatine phosphate (51% +/- 6% of control). There was no significant difference
      in myocardial function between the two groups (p > 0.05). The magnetic resonance
      spectroscopy data indicate ischemia occurred within 2 minutes of the initiation
      of retrograde perfusion. CONCLUSIONS: This study suggests that retrograde
      normothermic blood cardioplegia causes a transition of the myocardium to ischemic
      metabolism in the normal porcine heart.

PMID- 8526601
TI  - Perfadex is superior to Euro-Collins solution regarding 24-hour preservation of
      vascular function.
AB  - BACKGROUND: The aim of this study was to compare Perfadex with Euro-Collins
      solution regarding 24-hour preservation of endothelium-dependent relaxation and
      vascular smooth muscle function. METHODS: The infrarenal aorta of 72 isogenic
      rats was studied in organ baths as fresh controls, after 24 hours of cold (4
      degrees C) storage, and after 24-hour storage followed by transplantation and
      examination after 7 or 30 days. The thromboxane A2 analogue U-46619 was used to
      test contractility. Acetylcholine chloride was used to elicit endothelium
      dependent relaxation and papaverine hydrochloride, to elicit endothelium
      independent relaxation. RESULTS: With both solutions, all grafts were patent
      after 7 and 30 days. Vessels preserved in Euro-Collins solution for 24 hours lost
      95% (p < 0.001) of their contractility compared with fresh controls; 7 days after
      transplantation, they had regained 40% of initial contractility, and after 30
      days, there was no significant decrease in contractility. Vessels preserved in
      Perfadex manifested no significant decrease in contractility at any time.
      Endothelium-dependent relaxation could not be evaluated in vessels stored for 24
      hours in Euro-Collins solution because they had lost almost all contractility; 7
      days after transplantation, endothelium-dependent relaxation was reduced by 65%
      (p < 0.001), but at 30 days after transplantation, there was no significant
      decrease in endothelium-dependent relaxation. Vessels preserved in Perfadex for
      24 hours lost 17% (p < 0.05) of endothelium-dependent relaxation, but 7 and 30
      days after transplantation, there was no significant decrease in endothelium
      dependent relaxation. CONCLUSIONS: Perfadex, but not Euro-Collins solution, has
      the capacity to preserve vascular function after 24 hours of storage followed by
      in vivo reperfusion.

PMID- 8526602
TI  - Interaction of thyroid hormone and heparin in postischemic myocardial recovery.
AB  - BACKGROUND: Triiodothyronine (T3) administration can improve postischemic
      myocardial recovery. Heparin can interfere with cellular binding of T3.
      Introduction of heparin into an isolated heart model may interfere with this
      effect. METHODS: Four groups of 8 rat hearts were placed on a modified
      Langendorff apparatus. All groups underwent 15 minutes of perfusion with modified
      Krebs-Henseleit solution (KH), followed by 20 minutes of normothermic global
      ischemia and 30 minutes of reperfusion. Group I underwent reperfusion with KH.
      Group II underwent reperfusion with KH and 1 x 10(-6) mol/L of T3. In group III,
      hearts underwent preischemic perfusion with heparinized KH (1,000 U/L) and
      reperfusion with KH containing 1 x 10(-6) mol/L of T3 and 1,000 U/L of heparin.
      In group IV, rats were given heparin at 2,000 IU/kg 30 minutes before sacrifice,
      and isolated hearts were reperfused with KH and 1 x 10(-6) mol/L of T3. A latex
      balloon in the left ventricle monitored hemodynamic variables. RESULTS: Left
      ventricular developed pressure throughout postischemic reperfusion was greater in
      all the groups receiving T3 when compared with group I. Group II showed
      significantly greater recovery than either group III (p < 0.05) or group IV (p <
      0.05). CONCLUSIONS: Addition of T3 to the reperfusate enhances postischemic
      myocardial recovery in the isolated heart model, whereas addition of heparin
      reduces this effect.

PMID- 8526603
TI  - Treatment of dilated cardiomyopathy with dynamic cardiomyoplasty: the Heidelberg
      experience.
AB  - BACKGROUND: Data concerning the efficacy of dynamic cardiomyoplasty are still
      inconsistent, especially in terms of improvement of left ventricular function.
      METHODS: Between August 1990 and February 1994, eight isolated cardiomyoplasty
      procedures were performed in patients with cardiomyopathy (ejection fraction,
      0.14 to 0.32; New York Heart Association class III) and contraindications to
      heart transplantation. RESULTS: Follow-up was 41.1 +/- 14.1 months. One patient
      died 2 months and another 3 years after operation. Considerable symptomatic
      improvement was found in 6 of 7 patients, 3 of whom went back to work. One
      patient with severe pulmonary hypertension exhibited no improvement. Mean New
      York Heart Association-class decreased from 3.0 to 1.9 (p < 0.001).
      Echocardiography showed an increase in fractional shortening and in peak aortic
      flow velocity in all patients. Left ventricular ejection fraction increased from
      0.21 +/- 0.05 to 0.38 +/- 0.16 (n = 7, p < 0.015) at 1 year, to 0.37 +/- 0.18 (n
      = 6, p < 0.05) at 2 years, and to 0.36 +/- 0.19 (n = 5, not significant) at 3
      years. Pulmonary artery pressure tended to decrease over time. No significant
      change in exercise level or maximal oxygen consumption during treadmill testing
      was observed. CONCLUSIONS: Our preliminary results show that patients may exhibit
      an impressive clinical improvement after cardiomyoplasty, with only moderate
      changes in objective hemodynamic indices. We do not consider cardiomyoplasty an
      alternative to heart transplantation, but reserve it for patients with
      contraindications to heart transplantation.

PMID- 8526604
TI  - Massive calcification of the left atrium: surgical implications.
AB  - BACKGROUND: Massive calcification of the atrial walls ("porcelain atrium") is a
      rare condition that usually has been reported as an incidental radiologic
      findings. METHODS: Between January 1988 and June 1993, 971 patients underwent
      valvular operation at our institution; 21 patients showed extensive calcification
      of the left atrium. In 8 patients the calcification was massive, involving almost
      all the atrial surface. The diagnoses were established by radiology and were
      confirmed at operation. The mean age of these patients (4 men, 4 women) was 55 +/
      9.6 years. All had rheumatic valve disease, were on atrial fibrillation, and had
      undergone at least one operation previously. Pulmonary artery pressure was
      severely increased, even up to systemic levels, in all patients except 1. Total
      endoatriectomy of the left atrium and mitral valve replacement were performed. No
      patient was lost during the follow-up. RESULTS: Hospital mortality rate was 12.5%
      (1 patient) and 2 patients died in the late postoperative period. None of these
      deaths are attributable to the surgical procedure. CONCLUSIONS: In toto
      endoatriectomy of a massively calcified atrium is an easy to perform technique
      that helps to replace the mitral valve and close the atrial wall.

PMID- 8526605
TI  - Hemodynamics of different degrees of right heart bypass: experimental assessment.
AB  - BACKGROUND: Although their assessment could be of the utmost importance to
      determine the surgical treatment for patients with univentricular hearts,
      differences in ventricular performance between partial and complete right heart
      bypass remain to be defined. METHODS: Three different degrees of right heart
      bypass were investigated in 5 mongrel dogs: (1) superior vena cava to both
      pulmonary arteries shunt (SCP); (2) inferior vena cava to both pulmonary arteries
      shunt (ICP); and (3) both venae cavae to both pulmonary arteries shunt (BCP).
      Hemodynamic studies included evaluation of the cardiac index and left atrial
      pressure as a function of the degree of right heart bypass. RESULTS: By
      maintaining the mean left atrial pressure at 5 mm Hg, cardiac indexes were 1.98
      +/- 0.25, 1.67 +/- 0.29, and 1.33 +/- 0.21 L.min-1.m-2 for SCP, ICP, and BCP
      shunts, respectively (p = 0.001). When keeping the cardiac index constant, mean
      left atrial pressures were 5.2 +/- 0.8, 5.5 +/- 0.9, and 7 +/- 0.7 mm Hg for SCP,
      ICP, and BCP shunts, respectively (p = 0.001). CONCLUSIONS: Increasing degrees of
      right heart bypass are associated with a significant decrease in ventricular
      performance in this experimental model.

PMID- 8526606
TI  - Anti-CD11b monoclonal antibody improves myocardial function after six hours of
      hypothermic storage.
AB  - BACKGROUND: The shortage of pediatric heart donors often necessitates
      considerable travel time and, as a result, prolonged donor heart ischemia. This
      excessive hypothermic storage may contribute markedly to myocardial dysfunction
      in the recipient. METHODS: We investigated the role of leukocyte-endothelial
      interactions in this dysfunction in an isolated, immature (mean age, 11.8 +/- 1.6
      days) swine heart model using a monoclonal antibody against a leukocyte adhesion
      molecule. We studied a total of 20 hearts subjected to 6 hours of cardioplegic
      arrest at 4 degrees C. Group M1/70 (n = 6) received at reperfusion 15
      micrograms/mL of a monoclonal antibody F(ab')2 fragment to CD11b, the alpha
      subunit of the leukocyte adhesion molecule Mac-1. Group MB10.6 (n = 8) received
      15 micrograms/mL of the swine unreactive F(ab')2 MB10.6, and the third group
      received saline vehicle. RESULTS: Administration of M1/70 resulted in improved
      postischemic recovery of ventricular function compared with the two control
      groups (p < 0.05). CONCLUSIONS: These data implicate leukocyte-endothelial
      interactions mediated by the leukocyte adhesion molecule CD11b in myocardial
      dysfunction after long-term hypothermic ischemia. Specific antiadhesion
      strategies such as this may safely extend storage time for pediatric donor
      hearts.

PMID- 8526607
TI  - Unidirectional valve patch for repair of cardiac septal defects with pulmonary
      hypertension.
AB  - BACKGROUND: Congenital septal defects with a large left-to-right shunt often
      cause pulmonary hypertension, which complicates surgical repair of the defects.
      METHODS: Twenty-four patients with congenital cardiac septal defects and severe
      pulmonary hypertension had operation to close the septal defect using a
      unidirectional valve patch during a 3-year period. The ratio of systolic
      pulmonary artery pressure to systolic arterial blood pressure was near to or more
      than 1.0 in all patients. RESULTS: Two patients died in the hospital after
      operation, and there have been no deaths during intermediate term follow-up. Mean
      pulmonary artery pressure decreased from 80 +/- 12 mm Hg to 56 +/- 18 mm Hg. The
      ratio of pulmonary artery pressure to systemic arterial pressure dropped from 1.1
      +/- 0.1 mm Hg to 0.7 +/- 0.1 mm Hg. The unidirectional valve patch functioned
      allowing right to left shunting in 4 patients with a systolic pulmonary artery
      pressure more than systolic arterial blood pressure immediately after closure of
      a septal defect. The patch sealed or was effectively closed by the third
      postoperative day. There was impressive improvement in symptoms and exercise
      tolerance after operation during the 3-month to 3-year (mean, 1.1 year) follow-up
      period. CONCLUSIONS: The unidirectional valve patch is useful for management of
      patients having operation to close cardiac septal defects in the presence of
      severe pulmonary hypertension.

PMID- 8526608
TI  - Regression of hypertrophic cardiomyopathy after modified Konno procedure.
AB  - BACKGROUND: Septal myotomy-myectomy has been known to decrease the incidence of
      sudden death and produce regression in hypertrophic obstructive cardiomyopathy.
      Use of beta-blockers or calcium-channel blockers generally does not cause
      regression of the disease. METHODS: Having successfully performed modified Konno
      procedures in 13 patients with effective relief of diffuse subaortic stenosis, we
      applied the procedure in 2 patients with hypertrophic obstructive cardiomyopathy.
      Both patients (18 and 12 years old, respectively) presented with syncope, angina
      at rest, and dyspnea despite being on calcium channel blocker therapy. The
      echocardiographic outflow gradients were 66 mm Hg and 88 mm Hg, respectively,
      with moderate mitral regurgitation. RESULTS: Both patients had uneventful
      postoperative course. At 2 years and 1.5 years postoperatively, both patients
      were free of angina and syncopal episodes. Echocardiography showed absence of
      outflow gradients and mitral regurgitation. In 1 patient the septal and posterior
      wall thickness decreased from 3.4 and 1.7 cm preoperatively to 2.6 and 0.9 cm,
      respectively, postoperatively. In the other patient, the thickness decreased from
      2.4 and 0.9 cm preoperatively to 0.8 and 0.7 cm, respectively, postoperatively.
      Left atrial diameter decreased from 5.4 to 4.7 cm in 1 patient, 3.5 to 2.6 cm in
      the other. CONCLUSIONS: We believe that the modified Konno procedure could
      produce more effective relief of obstruction and, therefore, significant
      regression and further reduction in sudden death in hypertrophic obstructive
      cardiomyopathy. On the basis of our experience, albeit limited, we encourage its
      application.

PMID- 8526609
TI  - Comparative study of biological glues: cryoprecipitate glue, two-component fibrin
      sealant, and "French" glue.
AB  - BACKGROUND: Although biological glues have been used clinically in cardiovascular
      operations, there are no comprehensive comparative studies to help clinicians
      select one glue over another. In this study we determined the efficacy in
      controlling suture line and surface bleeding and the biophysical properties of
      cryoprecipitate glue, two-component fibrin sealant, and "French" glue containing
      gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG). METHODS: Twenty-four dogs
      underwent a standardized atriotomy and aortotomy; the incisions were closed with
      interrupted 3-0 polypropylene sutures placed 3 mm apart. All dogs had a 3- by 3
      cm area of the anterior wall of the right ventricle abraded until bleeding
      occurred. The animals were randomly allocated into four groups: in group 1 (n =
      6) bleeding from the suture lines and from the epicardium was treated with
      cryoprecipitate glue; in group 2 (n = 6) bleeding was treated with two-component
      fibrin sealant; group 3 (n = 6) was treated with GRFG glue; group 4 (n = 6) was
      the untreated control group. The glues were also evaluated with regard to
      histomorphology, tensile strength, and virology. RESULTS: The cryoprecipitate
      glue and the two-component fibrin sealant glue were equally effective in
      controlling bleeding from the aortic and atrial suture lines. Although the GRFG
      glue slowed bleeding significantly at both sites compared to baseline, it did not
      provide total control. The control group required additional sutures to control
      bleeding. The cryoprecipitate glue and the two-component fibrin sealant provided
      a satisfactory clot in 3 to 4 seconds on the epicardium, whereas the GRFG glue
      generated a poor clot. There were minimal adhesions in the subpericardial space
      in the cryoprecipitate and the two-component fibrin sealant groups, whereas
      moderate-to-dense adhesions were present in the GRFG glue group at 6 weeks. The
      two-component fibrin sealant was completely reabsorbed by 10 days, but
      cryoprecipitate and GRFG glues were still present. On histologic examination,
      both fibrin glues exhibited minimal tissue reaction; in contrast, extensive
      fibroblastic proliferation was caused by the GRFG glue. The two-component and
      GRFG glues had outstanding adhesive property; in contrast, the cryoprecipitate
      glue did not show any adhesive power. The GRFG glue had a significantly greater
      tensile strength than the two-component fibrin sealant. Random samples from both
      cryoprecipitate and the two-component fibrin glue were free of hepatitis and
      retrovirus. CONCLUSIONS: The GRFG glue should be used as a tissue reinforcer; the
      two-component fibrin sealer is preferable when hemostatic action must be
      accompanied with mechanical barrier; and finally, the cryoprecipitate glue can be
      used when hemostatic action is the only requirement.

PMID- 8526610
TI  - Permanent pacemaker for rejection episodes after heart transplantation: a poor
      prognostic sign.
AB  - BACKGROUND: The development of arrhythmias early or late after heart
      transplantation has been associated with acute and chronic rejection. This study
      aims to document the importance of this relationship and its value as a
      prognostic sign in those patients who required a permanent pacemaker for
      rejection episodes. METHODS: A retrospective analysis of 158 orthotopic heart
      transplantations performed in 157 patients between December 1988 and April 1995
      was done. The clinical course and the outcome of 6 patients who underwent
      insertion of a permanent pacemaker for bradyarrhythmias caused by acute or
      chronic allograft rejection were compared with the course and outcome of 9
      patients who had pacemaker placement as a result of sinus node dysfunction not
      associated with rejection. RESULTS: The mortality rate was 100% for patients
      whose indication for permanent pacing was severe acute or chronic rejection.
      Conversely, 8 of the 9 patients who underwent pacemaker placement for sinus node
      dysfunction not associated with rejection are long-term survivors; the one late
      death was due to a noncardiac cause. CONCLUSIONS: We observed a strong
      relationship between bradyarrhythmias requiring a permanent pacemaker and severe
      acute or chronic allograft rejection. This association suggests a poor prognosis
      and indicates that these patients should be managed aggressively. Such management
      includes close immunologic surveillance for cellular and humoral rejection,
      increased frequency of endomyocardial biopsies and coronary angiography, and
      early consideration for retransplantation.

PMID- 8526611
TI  - Acute changes in left ventricular geometry after volume reduction operation.
AB  - BACKGROUND: After surgical removal of a volume load, regression of myocardial
      mass proceeds slowly relative to diminution in ventricular cavity size, resulting
      in increased wall thickness and decreased cavity dimensions, which may affect the
      filling properties and performance of the heart. We investigated the acute
      changes in ventricular geometry that occur after the Fontan operation and hemi
      Fontan operation for tricuspid atresia, and compared them with closure of a
      ventricular septal defect in a two-ventricle heart. METHODS: We reviewed the
      results of echocardiography performed before and 8 +/- 7 days after (1) Fontan
      operation for tricuspid atresia (n = 9), (2) hemi-Fontan operation for tricuspid
      atresia (n = 10), and (3) closure of a ventricular septal defect (n = 13).
      Measurements were made from images of the left ventricle at end-diastole: (1)
      apical, septal, and posterior wall thickness; and (2) long- and short-axis cavity
      diameters, cross-sectional areas, and ventricular volume. Posterior wall
      thickness to cavity dimension ratio was calculated. RESULTS: Wall thickness
      increased in all groups, with the greatest degree of increase after the Fontan
      operation. Cavity measures decreased most dramatically after the Fontan
      operation, with less dramatic and equivalent changes noted after the hemi-Fontan
      operation and ventricular septal defect closure. Posterior wall thickness to
      cavity diameter ratios were equivalent in all before operation, increased after
      operation, and were greatest after the Fontan operation. CONCLUSIONS: Changes in
      ventricular geometry identified as an increase in wall thickness and a decrease
      in cavity dimension are most dramatic after the Fontan operation. Changes seen
      after the hemi-Fontan operation are of a milder degree, which may in part explain
      the excellent clinical course after this operation.

PMID- 8526612
TI  - L-arginine reduces endothelial inflammation and myocardial stunning during
      ischemia/reperfusion.
AB  - BACKGROUND: This study evaluated whether the nitric oxide precursor L-arginine
      could reduce ischemia/reperfusion injury by preventing leukocyte-endothelial
      interactions. METHODS: Normothermic regional ischemia was induced in the open
      chest working pig heart for 30 minutes followed by 90 minutes of reperfusion. A
      preischemic 10-minute intravenous infusion of 4 mg.kg-1.min-1 of L-arginine (n =
      12) was compared with 12 control pigs. Nitric oxide release was measured from the
      coronary sinus using an amperometric probe. Left ventricular function,
      malonaldehyde, creatine kinase, myocardial oxygen extraction, and the soluble
      adhesion molecules (intracellular adhesion molecule-1, endothelial leukocyte
      adhesion molecule-1, and vascular cell adhesion molecule-1) were measured.
      RESULTS: Nitric oxide release was significantly reduced from baseline throughout
      ischemia/reperfusion only in the control group. Systolic and diastolic function,
      and myocardial oxygen extraction were also significantly decreased during early
      reperfusion in the control compared with the L-arginine group. Peak creatine
      kinase release was not significantly different between groups. The incidence of
      ventricular fibrillation, malonaldehyde release, and soluble intracellular
      adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell
      adhesion molecule-1 were each significantly decreased during reperfusion in the L
      arginine group. CONCLUSIONS: L-Arginine reduced lipid peroxidation, plasma levels
      of soluble adhesion molecules, myocardial stunning, and arrhythmias. These
      results support an excessive endothelial injury/inflammatory response after
      regional ischemia/reperfusion that can be ameliorated through augmented nitric
      oxide.

PMID- 8526613
TI  - Three-dimensional echocardiography can simulate intraoperative visualization of
      congenitally malformed hearts.
AB  - BACKGROUND: The new technique of three-dimensional echocardiography can display
      the studied anatomy in any desired view plane. We sought to establish whether the
      reconstructions produced could provide views of the heart comparable with those
      obtained by the surgeon in the operating room. METHODS: Ninety-four patients,
      aged 1 day to 19 years (mean, 4.3 years), were examined. The ultrasound probe was
      placed either on the chest or subcostally and acquired 80 to 100 perpendicular
      parallel images of the heart with electrocardiographic and respiratory gating.
      Any plane, in particular oblique planes, within the data set can be analyzed.
      Whenever possible, the arrangement as seen by the surgeon was photographed, or
      heart specimens with similar intracardiac lesions were cut to simulate the view
      of the surgeons, to validate the echo-cardiographic reconstructions. RESULTS:
      Three-dimensional reconstruction of perimembranous ventricular septal defects,
      atrial septal defects, or anomalies of the atrioventricular valves could be
      displayed as viewed through an atriotomy. In similar fashion, reconstructions of
      muscular or doubly committed ventricular septal defects, along with obstruction
      of the right ventricular outflow tract, could be prepared as seen through a right
      ventriculotomy. Obstruction of the left ventricular outflow tract was shown as
      viewed through an aortotomy. Transthoracic three-dimensional echocardiography
      provided additional information in the prospective diagnosis of supravalvar
      mitral membrane, doubly committed subarterial ventricular septal defect, and
      subaortic stenosis caused by a restrictive ventricular septal defect in double
      inlet left ventricle. CONCLUSIONS: Three-dimensional echocardiography can
      simulate the display of the heart as seen by the surgeon in the operating room,
      and therefore can aid in better planning of surgical repair.

PMID- 8526614
TI  - Superoxide radical and xanthine oxidoreductase activity in the human heart during
      cardiac operations.
AB  - BACKGROUND: The results of clinical trials of xanthine oxidoreductase inhibition
      in cardiac surgery are encouraging, although studies have failed to localize the
      enzyme to the human heart and to localize free radical activity to fresh human
      heart. METHODS: We adapted a histochemical staining technique based on the
      reduction of nitro blue tetrazolium to formazan by superoxide radical. In six
      samples of right atrium graded blindly on a scale of 0 through 4, strong staining
      (median grade, 3) of the microvasculature was seen. This was blocked by
      allopurinol in paired sections (median grade, 1; p < 0.01). Chemiluminescence can
      be used as an index of superoxide radical activity. Atrial samples were taken
      from 13 patients at five time points during coronary bypass grafting and placed
      in buffered luminol. Then chemiluminescence was measured. RESULTS: A 15-fold rise
      in chemiluminescence (295.93 +/- 39.47 mV) was demonstrated during reperfusion
      compared with the control value (19.06 +/- 0.47 mV). Chemiluminescence at 1
      minute after release of the cross-clamp was significantly higher (p < 0.05) by
      analysis of variance versus values obtained before bypass and 1 minute before and
      30 minutes after reperfusion. CONCLUSIONS: In this study we have identified
      superoxide radical activity and a possible generating system (xanthine
      oxidoreductase) in the human heart.

PMID- 8526615
TI  - Retrograde cerebral perfusion: anatomic study of the distribution of blood to the
      brain.
AB  - BACKGROUND: Despite apparently good clinical results with retrograde cerebral
      perfusion during operation on the aortic arch, there is still concern about the
      real distribution of the blood injected in the superior vena cava to the brain,
      especially when the internal jugular vein is valvulated (88% of the cases). This
      anatomic study was carried out to determine how a liquid injected in the superior
      vena cava reaches the brain. METHODS: Three groups of adult cadavers (5, 5, and 3
      cases, respectively) were injected with latex, colored blue, through a cannula in
      the superior vena cava. In group I, 600 mL of latex was injected. Group II was
      identical except that a catheter had been inserted, before the injection, into
      the internal jugular vein to collapse the internal jugular vein valve, when
      existing. In group III, the azygos vein was ligated. RESULTS: The internal
      jugular vein was not valvulated in 2 cases in group I. In those 2 cases, latex
      was found up to the jugular foramen. In the other cases in group I, and in all
      cases in group II, where the internal jugular vein was valvulated, the following
      veins were injected: internal jugular vein up to the valve (almost no latex
      beyond), azygos vein, inferior vena cava, renal veins, rachidian and perimedullar
      venous plexuses, and venous sinuses of the brain. In group III, no opacification
      was observed beyond ligated azygos vein or valvulated internal jugular vein.
      CONCLUSIONS: Despite the fact that this study was carried out on cadavers, one
      can assume that, during retrograde cerebral perfusion, the azygos vein system is
      a major way to the central nervous system when the internal jugular vein is
      valvulated.

PMID- 8526616
TI  - Bypass graft for complex forms of isthmic aortic coarctation in adults.
AB  - BACKGROUND: Bypass grafting for complex forms of coarctation has been poorly
      documented as an alternative to decrease the high complication rate associated
      with anatomic repair. METHODS: Between mid-1980 and the end of 1994, 16 patients
      underwent bypass grafting for complex forms of isthmic aortic coarctation. Age
      ranged from 11 to 49 years (mean age, 28.4 +/- 13 years). Indications were
      atypical anatomic forms of coarctation (n = 12) and reoperation after multiple or
      complicated previous coarctation repair (n = 4). Lateroisthmic bypass grafts were
      performed in 14 patients and ascending aorta-descending aorta bypass grafts in 2.
      RESULTS: There was no hospital mortality. Morbidity consisted of postoperative
      paradoxical hypertension in 3 patients. There were no spinal cord complications.
      One death 10 years postoperatively was unrelated to the surgical technique. One
      patient successfully underwent ascending aorta-descending aorta bypass grafting
      for a false aneurysm 10 years after lateroisthmic grafting. All patients were
      asymptomatic and all grafts, patent after a mean follow-up of 5.7 +/- 4 years.
      CONCLUSIONS: On the basis of these results, bypass grafting appears to be a safe
      alternative in this select group of patients. The lateroisthmic bypass graft is
      the procedure of first choice, and the ascending aorta-descending aorta bypass
      graft should be reserved for failure of previous lateroisthmic bypass grafting.

PMID- 8526617
TI  - Reoperation for recurrent aortic coarctation.
AB  - BACKGROUND: Recurrence of stenosis is a complication of coarctation repair
      associated with major long-term morbidity. Persistent or exercise-provoked
      hypertension may indicate recurrent coarctation. Patients failing or not amenable
      to balloon dilation should be managed surgically. METHODS: A retrospective chart
      review was performed. RESULTS: Forty-three patients were identified as having
      undergone repeat surgical intervention for recurrent aortic coarctation between
      the years 1976 and 1993 at The Hospital for Sick Children in Toronto. Seventy
      percent of the children had other congenital cardiac anomalies. Eighty-six
      percent of patients initially treated by subclavian flap aortoplasty or end-to
      end anastomosis were managed at reoperation by patch aortoplasty, and 26% of
      patients also required augmentation of the transverse arch (under hypothermic
      circulatory arrest) for accompanying hypoplasia. Three patients underwent a
      second reoperation; all were treated at this reoperation with tube graft
      interposition. CONCLUSIONS: No ischemic spinal injury occurred in patients
      managed with either simple proximal aortic cross-clamping or cardiopulmonary
      bypass. No patient treated with transverse arch augmentation required further
      surgical intervention. Mortality at reoperation was 7% (3 patients), similar to
      that of first-time coarctation repair. At follow-up (mean duration, 4.5 years),
      57% of patients are normotensive, with no measurable arm-leg gradient.

PMID- 8526618
TI  - Can improved microvascular perfusion be achieved by using both antegrade and
      retrograde cardioplegia?
AB  - BACKGROUND: The complete and uniform distribution of cardioplegia to the
      microvasculature of the heart is considered critical for myocardial protection.
      This study explores the hypothesis that enhanced microvascular perfusion can be
      achieved by using both antegrade and retrograde cardioplegia. METHODS: Infant
      piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised,
      and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then
      perfused retrograde with an inert intracapillary marker (NTB-2). Six of these
      hearts served as controls (group 1) to anatomically demonstrate the degree of
      capillary perfusion achieved by the retrograde delivery route. Nine experimental
      hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia
      to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde
      delivery techniques. Sections of the left ventricular free wall and anterior-mid
      interventricular septum were taken and examined by light microscopy at four
      separate sites (average, 126 capillaries per section). RESULTS: In control
      hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal
      capillaries were perfused by retrograde cardioplegia. After antegrade blood
      cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the
      ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the
      septum. CONCLUSIONS: In this experimental model, antegrade blood cardioplegia did
      not coperfuse (and therefore washout) 12.5% to 14% (p < 0.05) of capillaries
      perfused by retrograde cardioplegia. This suggests that an additional 12.5% to
      14% of capillaries within the myocardium may receive cardioplegia if retrograde
      cardioplegia is used in addition to antegrade cardioplegia. We conclude that by
      combining both antegrade and retrograde cardioplegia, there is a potential for
      enhanced overall microvascular perfusion.

PMID- 8526619
TI  - Ball valve (Smeloff-Cutter) aortic valve replacement without anticoagulation.
AB  - BACKGROUND: Because of the difficulty of permanent anticoagulation in our young
      population, Smeloff-Cutter ball valves have been used since 1986 at our
      institution for aortic valve replacement in selected patients without permanent
      anticoagulation therapy. METHODS: The availability of a satisfactory follow-up
      system since July 1988 suggested a study of all 47 patients operated on since
      then and followed for a mean of 43.2 months (range, 16 to 78 months). Mean age
      was 26.3 years, 98% were in sinus rhythm, and 16 patients (34%) had concomitant
      mitral repair. RESULTS: There were no hospital deaths. Three patients were lost
      to follow-up at a mean of 27 months. Four late deaths occurred (8.5%), two of
      them sudden, with actuarial survival at 6 years of 91% +/- 4.3%. There were a
      total of five embolic events (2.9%/patient-year). For isolated aortic valve
      replacement only, with antiaggregant therapy (n = 29), the incidence was
      0.9%/patient-year. For all patients receiving antiaggregant agents (n = 43), it
      was 3.02%/patient-year. There were no known cases of valve thrombosis.
      Reoperation was required in 5 patients. CONCLUSION: Aortic valve replacement with
      the Smeloff-Cutter ball valve might be a valid alternative for young patients
      unable to maintain regular anticoagulation.

PMID- 8526620
TI  - Disparity in blood activation by two different heparin-coated cardiopulmonary
      bypass systems.
AB  - BACKGROUND: Several studies have indicated reduced "blood activation" in heparin
      coated cardiopulmonary bypass systems. The present study compares the effect of
      two different heparin coatings on different blood activation indices. METHODS:
      Low-risk patients (n = 40) were randomized to coronary artery bypass grafting
      using cardiopulmonary bypass with surfaces coated entirely by either the Duraflo
      II heparin coat or the Carmeda Biological Active Surface, or with identical
      uncoated equipment. In all cases, a standard systemic heparin dosage was used.
      Complement activation (C3 activation products C3bc and C3a and formation of fluid
      phase terminal SC5b-9 complement complex), neutrophil activation (lactoferrin and
      myeloperoxidase), and lytic inhibitors (vitronectin and clusterin) were
      quantified during cardiopulmonary bypass and 6 hours postoperatively. RESULTS:
      Heparin coating by either method reduced the formation of terminal SC5b-9
      complement complex and the release of lactoferrin and myeloperoxidase compared
      with uncoated systems. Lactoferrin and myeloperoxidase levels increased
      significantly during cardiopulmonary bypass in the Duraflo II group, whereas no
      significant increase was observed in the Carmeda Biological Active Surface group.
      The least formation of terminal SC5b-9 complement complex and neutrophil
      activation was observed with the Maxima Carmeda Biological Active Surface-coated
      equipment. The vitronectin and clusterin concentrations were significantly less
      reduced in the Duraflo II compared with the control group. This study underlines
      the importance of terminal SC5b-9 complement complex as a suitable marker in the
      evaluation of complement activation during cardiopulmonary bypass. CONCLUSIONS:
      Both heparin coatings reduce blood activation, probably more so with Carmeda
      Biological Active Surface than with Duraflo II.

PMID- 8526621
TI  - Cardiac anatomy in patients undergoing the Fontan procedure.
AB  - BACKGROUND: Controversies in nomenclature, especially of hearts with "single
      ventricle," have clouded discussion and understanding of the anatomy. Many
      patients with such malformations are submitted to the Fontan procedure as
      definitive surgical palliation. The spectrum of anatomy among these patients is
      wide and deserves analysis in an effort to provide a simple framework for
      description and to eliminate confusion. METHODS: We reviewed 138 successive
      patients undergoing the Fontan operation at one institution to demonstrate the
      variability in pathology. RESULTS: Only 89 patients (65%) had a univentricular
      type of atrioventricular connection. All but 5 patients had two ventricular
      chambers. Among the 49 patients with biventricular atrioventricular connections,
      43 had a hypoplastic ventricle that precluded a biventricular repair.
      CONCLUSIONS: Full understanding of the malformations that may preclude a
      "biventricular" repair and hence necessitate a Fontan procedure requires
      knowledge of the different forms of univentricular atrioventricular connection
      that, although usually associated with two ventricular chambers, are seldom
      amenable to a "two-pump repair." Understanding of those types of "biventricular
      heart" that preclude a two-pump repair (eg, severe hypoplasia of the left
      ventricle or the right ventricle) or are associated with high risks (eg,
      straddling atrioventricular valve) is also important.

PMID- 8526622
TI  - Congenital diaphragmatic hernia: experience in a single institution from 1978
      through 1994.
AB  - BACKGROUND: Congenital diaphragmatic hernia continues to be a difficult
      management problem. Essentially all information on the condition has been
      compiled in a retrospective manner due to the individualized care that each
      infant must undergo. We contribute a review of our patients to add to the current
      fund of knowledge and to assess our experience before and since the introduction
      of extracorporeal membrane oxygenation in our institution. METHODS: This is a
      review of records of infants with congenital diaphragmatic hernia treated from
      1978 through 1994. Repair has generally been accomplished early with only one
      repair being accomplished with an infant placed on extracorporeal membrane
      oxygenation preoperatively. RESULTS: Overall survival was 63%. Survival was 42%
      before extracorporeal membrane oxygenation becoming available in our region in
      1986, and 75% afterward. Since 1986, 16 of 33 (48%) infants have required
      extracorporeal membrane oxygenation and 73% have survived. CONCLUSIONS: Overall
      survival in our series is comparable with that of other reported series. There
      appears to be an improvement in survival since the introduction of extracorporeal
      membrane oxygenation. Our present practice of early repair, and postrepair
      extracorporeal membrane oxygenation if needed, results in a survival rate
      comparable with that of currently available series reports regardless of the
      method of treatment reported.

PMID- 8526623
TI  - Thoracoscopic staging of esophageal cancer: a prospective, multiinstitutional
      trial. Cancer and Leukemia Group B Thoracic Surgeons.
AB  - BACKGROUND: Lymph node metastasis has been shown to be an important
      prognosticator in esophageal cancer. A prospective, multiinstitutional study of
      thoracoscopic lymph node staging in patients with biopsy-proven esophageal cancer
      was undertaken at University of Maryland, Medical University of South Carolina,
      and Brigham and Women's Hospital. METHODS: Forty-nine patients underwent
      thoracoscopic staging between September 1991 and August 1993. Five procedures
      were incomplete due to adhesions. Preoperative computed tomography, magnetic
      resonance imaging, esophageal ultrasound, and bronchoscopy were performed. After
      our initial experience with the left side of the chest, thoracoscopic staging was
      done through the right side of the chest unless specific indications dictated
      otherwise. Beginning in January 1993 routine laparoscopic/mini-laparotomy lympho
      node staging of the celiac axis was performed. RESULTS: Satisfactory
      thoracoscopic lymph node staging was achieved in 44 patients (95%). Of 33
      patients undergoing esophageal resection, 29 were correctly staged (88%). Since
      initiating concomitant laparoscopic lymph node staging, we have correctly staged
      all of the last 9 patients with regard to celiac lymph nodes as well. Information
      regarding T status obtained at thoracoscopy was as follows: 3 patients were
      correctly "downstaged" to T3 despite preoperative noninvasive tests suggesting
      T4. In 2 patients thoracoscopy correctly predicted T4 invasion, whereas in 2
      patients, thoracoscopy missed T4 lesions. CONCLUSIONS: Thoracoscopy is a valuable
      tool for staging intrathoracic tumors. Preoperative staging of esophageal cancer
      may allow better allocation of adjuvant therapy. This pilot study suggests that
      thoracoscopic staging can correctly predict thoracic lymph node status with high
      accuracy and aid in better defining T status.

PMID- 8526624
TI  - Prevalence and outcome of bronchiolitis obliterans syndrome after lung
      transplantation. Washington University Lung Transplant Group.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the main cause of late
      morbidity and mortality in lung transplantation. This study was designed to
      accurately determine the prevalence of this syndrome of chronic lung allograft
      dysfunction (which is presumed to be due to chronic rejection). METHODS: A
      retrospective analysis was done of 212 consecutive lung transplantations
      performed at Barnes Hospital between July 1988 and March 1994 to characterize the
      prevalence and course of BOS. One hundred eighty-seven transplant recipients
      survived at least 3 months after transplantation, putting them at risk for BOS.
      Recipients free of BOS (group I) were distinguished from those with BOS (group
      II) based on the presence of declining spirometry (forced expiratory volume in 1
      second persistently less than 80% of previous baseline) or histologic
      obliterative bronchiolitis in group II. RESULTS: There were 110 transplantations
      in group I (59%) and 77 in group II (41%). At follow-up, BOS was detected using
      the following criteria: declining forced expiratory volume in 1 second alone, 40
      of 77 (52%); positive histologic results alone, 7 of 77 (9.1%); and both, 30 of
      77 (38.9%). Declining spirometry was the most common initial sign of BOS onset
      (57 of 77, 74%). There were no differences between groups with respect to age,
      sex, indication for transplantation, or type of transplantation performed. The
      mortality rate was significantly higher with BOS (group II, 22 of 77 [28.6%]
      versus group I, 8 of 110 [7.3%]; p = 0.001) and was not related to either the
      type of transplantation performed or the indication for transplantation. Follow
      up of group II (mean 35.1 months; range, 7.1 to 63.7 months) showed a delay until
      BOS onset (16.1 +/- 1.2 months); when BOS was fatal, death ensued within 11.5 +/-
      2.4 months of its onset. Comparison of the first and last quartiles of recipients
      in this series (QTR1 versus QTR4, 53 patients in each) demonstrated a higher
      prevalence of BOS in QTR1 (24 with BOS of 43 at risk [55.8%] versus QTR4, 5 with
      BOS of 52 at risk [9.6%]; p < 0.001) and a worse BOS functional score in QTR1
      (2.2 +/- 0.2 versus QTR4, 0.8 +/- 0.2; p = 0.007). CONCLUSIONS: (1) Bronchiolitis
      obliterans syndrome is truly a clinical syndrome, not simply a pathologic entity;
      (2) BOS displays considerable latency in onset and progression; (3) lung
      transplant recipients must therefore be followed up for a sufficient interval to
      determine the actual prevalence and mortality rate of BOS; and (4) the prevalence
      and mortality rates of BOS are higher than previously appreciated, exceeding 50%
      and 40%, respectively.

PMID- 8526625
TI  - Lung tumor growth correlates with glucose metabolism measured by fluoride-18
      fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: The growth rate, or doubling time, of radiographically indeterminate
      pulmonary abnormalities is an important determinant of malignancy. Prospective
      calculation of doubling time, however, delays diagnosis and treatment. Positron
      emission tomography (PET) using the glucose analogue fluoride-18
      fluorodeoxyglucose (FDG) measures the enhanced glucose uptake characteristic of
      neoplastic cells. We postulated that if FDG activity correlates with doubling
      time, then PET may allow prompt diagnosis of lung cancer. METHODS: From March
      1992 to July 1993, all patients with indeterminate focal pulmonary abnormalities
      were eligible for FDG PET imaging. In 53 patients, serial chest radiographs or
      computed tomograms were available and doubling time was computed. The FDG
      activity within the lesion was expressed as a standardized uptake ratio. RESULTS:
      The mean standardized uptake ratio (+/- SD) was 5.9 +/- 2.7 in 34 patients with
      cancer, versus 2.0 +/- 1.7 in 19 with benign disease (p < 0.001). Using a
      criterion of standardized uptake ratio 2.5 or greater for malignancy, the
      accuracy of PET was 92% (49 of 53). The standardized uptake ratio was
      significantly correlated with doubling time (r = -0.89; p = 0.002). CONCLUSION:
      These data suggest a direct relation between tumor growth and FDG uptake in lung
      cancer. The technique of FDG PET demonstrates exceptional accuracy and may permit
      prompt diagnosis of lung cancer.

PMID- 8526626
TI  - Resection of sternal tumors: extent, reconstruction, and survival.
AB  - BACKGROUND: Resection of sternal tumors may be tailored to the patient and the
      location of the malignancy. METHODS: We reviewed our results of sternectomy
      (typically 5-cm margins) performed in 30 patients over a 10-year period. RESULTS:
      Thirteen patients had primary sternal sarcoma (six chondrosarcoma, five
      osteosarcoma, two other); 10 patients had local recurrence from breast cancer; 4
      patients had metastases; 3 patients had other (two osteoradionecrosis, one
      malignant fibrous histiocytoma). Morbidity occurred in 8 patients (26.7%): wound
      dehiscence, 2; wound infection, 1; hemorrhage, 1; pneumonia, 1; prolonged air
      leak, 1; empyema, 1; and bronchopleural fistula, 1. One patient, with multiple
      metastases, died from adult respiratory distress syndrome on day 25 (overall
      mortality, 3.3%; 1 of 30). The area of reconstruction ranged from 35 to 264 cm2.
      The technique of reconstruction included muscle flap alone in 13 patients; muscle
      flap and mesh, 9; muscle flap and rigid prosthesis (Marlex methylmethacrylate),
      7; or other, 1 patient. Nineteen patients (63%) were extubated within 24 hours
      after operation. Median intensive care unit stay was 2 days; median
      hospitalization, 6 days. Late local recurrence after resection occurred in 6
      patients; 4 from breast cancer (3 patients had concurrent distant metastases).
      Five-year actuarial survival after primary tumor resection was 73% and 33% after
      resection of recurrent breast cancer (median, 21 months). CONCLUSIONS: Partial
      sternectomy may be performed for primary sternal tumors with short
      hospitalization and good local control. Wider local excision or total sternectomy
      may minimize local re-recurrence of breast carcinoma to the sternum.

PMID- 8526627
TI  - CD18-independent mechanism of neutrophil emigration in the rabbit lung after
      ischemia-reperfusion.
AB  - BACKGROUND: Reperfusion of ischemic lung causes an inflammatory pulmonary
      vascular injury characterized by increased vascular permeability and migration of
      inflammatory cells into the alveoli. Migration of neutrophils into the alveolus
      during reperfusion after 24 hours of unilateral pulmonary artery occlusion has
      been shown to be in part dependent on the CD18 adhesion molecule on the cell
      surface. The current study investigated whether reperfusion lung injury after a 1
      hour period of complete lung ischemia was CD18 dependent. METHODS: Eighteen
      rabbits were assigned to one of three groups. Groups 1 and 2 were subjected to
      one hour of in situ right hilar occlusion followed by 2 hours of reperfusion.
      Group 3 was subjected to identical surgical dissection but the right hilum was
      never occluded. Group 1 rabbits received saline solution (1 mL/kg) before hilar
      occlusion and group 2 rabbits, monoclonal antibody 60.3, a blocking antibody for
      the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the
      antibody-treated rabbits, flow cytometry was performed on blood neutrophils
      before and after administration of the antibody and 120 minutes after
      reperfusion. RESULTS: The rabbits in groups 1 and 2 had significantly increased
      alveolar neutrophil infiltrate and increased pulmonary vascular resistance
      compared with the rabbits in group 3. However, there was no significant
      difference between group 1 (saline solution treated) and group 2 (antibody
      treated). Antibody treatment did not block migration of neutrophils into the
      alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was
      upregulated after reperfusion and that CD18 was fully blocked after antibody
      treatment for the duration of the study. CONCLUSIONS: We conclude that a 1-hour
      period of warm ischemia followed by reperfusion results in upregulation of CD18
      but that emigration of the neutrophils into the alveoli is not CD18 dependent in
      this injury.

PMID- 8526628
TI  - Membranous tracheal rupture after endotracheal intubation.
AB  - BACKGROUND: Tracheobronchial rupture after tracheal intubation has been
      infrequently reported. We report 6 cases of membranous tracheal rupture after
      endotracheal intubation treated at our institution over 7 years. METHODS:
      Overinflation of the tracheal cuff was speculated to be a frequent cause of the
      tracheal damage because the lesion was always a linear laceration of the
      posterior membranous wall. The diagnosis was suspected on the basis of common
      signs such as subcutaneous emphysema, respiratory distress, pneumomediastinum,
      and pneumothorax. Fiberoptic bronchoscopy was the best means of confirming the
      diagnosis and determining the location and extent of the lesion. In 5 patients,
      extensive laceration with severe respiratory disorders required emergent repair
      through a right posterolateral thoracotomy. RESULTS: There were two postoperative
      deaths unrelated to the tracheal lesion. A patient with a small tracheal defect
      and favorable clinical presentation showed a rapid positive outcome after
      conservative treatment. CONCLUSIONS: Tracheal intubation-related airway ruptures
      are rare but probably underestimated. Early recognition and emergent repair are
      essential, because failure to do so could result in potentially lethal events.

PMID- 8526629
TI  - Soft-tissue reconstruction in thoracic surgery.
AB  - BACKGROUND: Reconstructive techniques using omental and myocutaneous flaps are
      widely used in the treatment of infected sternotomy wounds. To illustrate their
      wider role in thoracic reconstruction, we have retrospectively reviewed our
      experience over the last 5 years. METHODS: We used complex omental and
      myocutaneous flaps in 30 patients: 19 men and 11 women with a mean age of 53 +/-
      4 years (range, 43 to 75 years). In 18 patients, these techniques were used to
      provide soft-tissue cover after chest wall resection, and in 12 cases complex
      myocutaneous flaps were used to obliterate chronic intrathoracic cavities. Rectus
      muscle was used in 11 of 24 muscle flaps, and omentum was used in 12 cases. There
      were 23 rotational flaps and seven free myocutaneous flaps with microvascular
      anastomosis. RESULTS: There were no operative deaths, and there were three
      complications. In 2 patients with infected lesions, loss of the free flap
      required subsequent revision. In 1 patient, infection developed underneath a
      prosthesis, which was treated with drainage and rib resection. In all other
      cases, the primary aim of the operation was achieved without complications.
      CONCLUSIONS: The vascularity of the omentum should encourage its wider use,
      especially when infection exists preoperatively. Excellent results can be
      achieved when using the rectus muscle as a complex myocutaneous flap. The use of
      free flaps should be reserved for difficult cases and used only in the absence of
      infection.

PMID- 8526630
TI  - Free radical-mediated vascular injury in lungs preserved at moderate hypothermia.
AB  - BACKGROUND: Early allograft dysfunction remains a frequently encountered problem
      in clinical lung transplantation. Lung ischemia-reperfusion injury is associated
      with increased vascular permeability, which may be due in part to oxygen (O2)
      free radicals. However, it is not clear whether O2 free radicals are produced
      during ischemia under storage conditions in clinical lung transplantation.
      METHODS: Using an isolated ex vivo rabbit lung model, we studied the effects of
      preservation temperature on pulmonary capillary filtration coefficient (Kf) and
      lipid peroxidation in rabbit lungs inflated with 100% O2 after preservation with
      or without the O2 free radical scavenger dimethylthiourea. New Zealand white
      rabbits weighing 2.7 to 3.1 kg were intubated and ventilated with room air or
      100% O2 (tidal volume = 25 mL). After heparinization and sternotomy, the
      pulmonary artery was flushed with low-potassium-dextran-1% glucose solution (200
      mL). The heart-lung block was excised, submerged, and stored for 24 hours at 1
      degree or 10 degrees C. After 24-hour preservation, the heart-lung block was
      suspended from a strain-gauge force transducer and ventilated with room air. The
      pulmonary artery cannula was connected to a reservoir of hetastarch solution. The
      lungs were flushed briefly with the hetastarch solution, and the reservoir was
      raised sequentially at 8-minute intervals to achieve 1.0 to 1.5 mm Hg increments
      in pulmonary artery pressure. Lung weight gain, airway pressure, pulmonary artery
      pressure, and left atrial pressure were measured continuously. The slope of
      steady-state lung weight gain was used to determine Kf (g.min-1.cm H2O-1 x 100 g
      1 wet weight). RESULTS: Twenty-four-hour lung preservation at both 1 degree and
      10 degrees C increased Kf. A similar increase in Kf was observed in lungs stored
      at 1 degree C while inflated with 100% O2. However, a significant increase in Kf
      was observed when lungs inflated with 100% O2 were stored at 10 degrees C. This
      increase in Kf was ameliorated by dimethylthiourea. Thiobarbituric acid-reactive
      substance levels were increased in lungs stored at 10 degrees C while inflated
      with 100% O2. This finding was eliminated by dimethylthiourea. CONCLUSIONS: These
      results indicate that free radical injury occurs during the ischemic phase when
      lungs are stored at moderate hypothermia while inflated with 100% O2.

PMID- 8526631
TI  - Investigation for mediastinal disease in patients with apparently operable lung
      cancer. Canadian Lung Oncology Group.
AB  - BACKGROUND: The optimal approach to the investigation of mediastinal disease in
      patients with apparently operable non-small cell carcinoma of the lung is
      controversial. METHODS: We conducted a randomized, controlled trial in thoracic
      surgery services at mainly academic tertiary and secondary care general
      hospitals. We recruited 685 patients with apparently operable, suspected or
      proven, non-small cell carcinoma of the lung who underwent either mediastinoscopy
      or computed tomography. Depending on the apparent presence or absence of
      mediastinal nodes of greater than 1 cm, patients undergoing computed tomography
      either underwent mediastinoscopy or went directly to thoracotomy. The primary
      outcome was thoracotomy without cure, defined as resection with recurrence.
      Secondary outcomes included thoracotomies undertaken in patients with benign
      disease and costs of the two strategies. RESULTS: The relative risk of
      thoracotomy without cure in patients in the computed tomography group was 0.95
      (95% confidence interval, 0.75 to 1.19). The relative risk of thoracotomy without
      cure or thoracotomy in patients with benign disease was 0.88 (95% confidence
      interval, 0.71 to 1.10). The mediastinoscopy strategy cost $708 more per patient
      (95% confidence interval, -$723 to $2,140). CONCLUSIONS: The computed tomography
      strategy is likely to produce the same number of or fewer unnecessary
      thoracotomies in comparison with doing mediastinoscopy on all patients, and is
      also likely to be as or less expensive.

PMID- 8526632
TI  - Pulmonary artery perfusion of doxorubicin with blood flow occlusion:
      pharmacokinetics and treatment in a metastatic sarcoma model.
AB  - BACKGROUND: We compared pharmacokinetics, toxicity, and treatment efficacy of
      pulmonary artery perfusion of low-dose doxorubicin with blood flow occlusion to
      intravenous doxorubicin injection in a metastatic sarcoma model in the rat.
      METHODS: Animals received left pulmonary artery perfusion with 0.1, 0.2, or 0.5
      mg/kg doxorubicin at a rate of 0.1 mL/min for 1 minute with 20 minutes of blood
      flow occlusion. Doxorubicin levels of the lung, heart, and serum were assayed.
      Body weights after treatment were recorded and right pneumonectomy was performed.
      The results were compared with those in rats that received 5 mg/kg doxorubicin by
      intravenous injection or the saline group. Pulmonary sarcoma metastases were
      treated with 0.5 mg/kg doxorubicin through lung perfusion or intravenously, or
      with saline solution. RESULTS: Doxorubicin levels in the lung, heart, and serum
      were 112.1 +/- 9.2 micrograms/g, 1.7 +/- 0.2 microgram/g, and 0.3 +/- 0.1
      microgram/mL in the group with 0.5 mg/kg doxorubicin perfusion, versus 24.8 +/-
      1.9 microgram/g, 10.1 +/- 1.3 microgram/g, and 0.7 +/- 0.2 microgram/mL in the
      intravenous group (p < 0.05). Animals had normal growth patterns and survived
      after right pneumonectomy in the perfused group, whereas the intravenous group
      failed to thrive. No tumors were found or a significant reduction in nodules was
      noted in the lungs treated with perfusion as compared with untreated right lungs
      or the intravenous and saline groups. CONCLUSION: This chemotherapy model has
      important pharmacokinetic advantages and causes an increased treatment response
      for pulmonary metastatic sarcoma with minimal systemic and local toxicity as
      compared with systemic doxorubicin administration.

PMID- 8526633
TI  - Combined valve replacement and coronary bypass grafting in osteogenesis
      imperfecta.
AB  - Open cardiac procedures in osteogenesis imperfecta have been associated with a
      high mortality rate. A patient with osteogenesis imperfecta underwent successful
      aortic valve replacement and coronary artery bypass grafting along with closure
      of a patent foramen ovale in preparation for a planned hip replacement.

PMID- 8526634
TI  - Acute aortic dissection in a patient with osteogenesis imperfecta.
AB  - A case of osteogenesis imperfecta complicated with acute type A aortic dissection
      is presented. Emergency graft replacement of the ascending aorta was performed
      successfully despite the anticipated difficulties with tissue friability.
      Therefore, such an operation is suggested to be worthy of consideration and
      feasible in patients with osteogenesis imperfecta.

PMID- 8526635
TI  - Surgical repair of complete atrioventricular septal canal defects with absent
      posterior leaflet.
AB  - We report 2 cases of absence of the posterior (left mural) leaflet in complete
      atrioventricular septal defect. Closure of the atrioventricular septal defect was
      successfully accomplished in both cases. We describe the technique of left
      atrioventricular valve repair that led to a competent reconstructed valve.

PMID- 8526636
TI  - Aortic root replacement and extraanatomic bypass for interrupted aortic arch in
      an adult.
AB  - We describe an unusual case of interrupted aortic arch, aneurysmal ascending
      aorta, and aortic regurgitation in a 24-year-old man. He presented with general
      malaise, weakness of his legs, and hypertension. A single-stage operation was
      performed in which the aortic root was replaced with concomitant extraanatomic
      bypass of the interrupted segment of the aortic arch. He made a full recovery and
      has returned to work.

PMID- 8526637
TI  - Surgical closed atrial septotomy under transesophageal guidance.
AB  - An infant with pulmonary atresia and intact ventricular septum is presented who,
      after initial patch reconstruction of the right ventricular outflow tract and
      bidirectional cavopulmonary anastomosis through a fifth median sternotomy,
      underwent an echocardiographically guided closed atrial septotomy, which resulted
      in marked long-term clinical improvement. The technique of intraoperative
      transesophageal echocardiography as used in the presented case represents an
      expanded role for this diagnostic modality in congenital cardiac surgery.

PMID- 8526638
TI  - Retrograde pulmonary embolectomy by flushing of the pulmonary veins.
AB  - A glue embolization of a cerebral arteriovenous malformation in a 3-year-old boy
      was complicated by a massive pulmonary embolus due to glue entering the venous
      circulation. Attempted pulmonary embolectomy via pulmonary arteriotomy after
      emergency cardiopulmonary bypass was unsuccessful. However, retrograde flushing
      of the pulmonary veins with cold saline solution produced large quantities of
      embolus through the pulmonary arteriotomy. Bypass was discontinued uneventfully
      with no residual cardiopulmonary problems.

PMID- 8526639
TI  - Heart transplantation for Chagas' cardiomyopathy.
AB  - We present 2 patients who underwent orthotopic heart transplantation for end
      stage Chagas' cardiomyopathy. Despite immunosuppressive therapy, postoperative
      prophylaxis with nifurtimox appeared to prevent Trypanosoma cruzi reactivation.
      Neither patient has shown signs of Chagas' myocarditis, and both are clinically
      well 12 and 72 months after transplantation. The successful outcome of our
      patients suggests that heart transplantation is a reasonable therapeutic option
      in patients with end-stage Chagas' cardiomyopathy.

PMID- 8526640
TI  - Cardiac allograft failure: successful use of biventricular assist device.
AB  - Nonspecific primary allograft dysfunction is an important cause of perioperative
      death in cardiac transplant recipients. We report a case of severe nonspecific
      allograft dysfunction that was ultimately reversible after 18 days of
      biventricular mechanical circulatory support. Allograft recovery was
      echocardiographically recognized by a positive inotropic response to
      isoproterenol and milrinone. This case illustrates the potential for recovery of
      even extreme allograft dysfunction.

PMID- 8526641
TI  - Vascular ring causing symptomatic tracheal compression in adulthood.
AB  - A 32-year-old woman was referred for evaluation of a 3-year history of exertion
      dyspnea. An anomalous vascular ring created by a right aortic arch with mirror
      image branching, left descending aorta, and aortic diverticulum narrowed the
      trachea circumferentially. This feature was surgically approached through a right
      posterolateral thoracotomy, and simple amputation of the aortic diverticulum
      resulted in immediate symptomatic relief.

PMID- 8526642
TI  - Late development of esophageal compression from a vascular ring.
AB  - Severe esophageal compression due to a vascular ring rarely develops after
      childhood. We report a case of a 57-year-old man with recent onset of dysphagia
      associated with right aortic arch, right descending aorta, and retroesophageal
      left subclavian artery arising from an arch diverticulum. Surgical repair was
      recommended for relief of symptoms and to prevent rupture of the diverticulum.
      The patient underwent left thoracotomy, division of the ligamentum arteriosum,
      and excision of the arch diverticulum. The left subclavian artery was reimplanted
      into the left common carotid artery through a separate neck incision. The patient
      had total relief of dysphagia postoperatively.

PMID- 8526643
TI  - Leiomyosarcoma of the superior vena cava and azygos vein.
AB  - A 40-year-old woman presented with facial swelling and pressure sensation of the
      ears and sinuses. Chest roentgenography revealed a right paratracheal mass, which
      was confirmed by a venogram, and transjugular biopsy showed low-grade
      leiomyosarcoma. The superior vena cava was resected and reconstructed using a
      spiral vein graft. Pathologic evaluation revealed a low-grade leiomyosarcoma
      arising from both the superior vena cava and the azygos vein with clear margins.

PMID- 8526644
TI  - Silicone thorax: a complication of tube thoracostomy in the presence of mammary
      implants.
AB  - Rupture of silicone breast implants is usually either iatrogenic or due to
      trauma. We present a case of blunt chest wall trauma in a patient with bilateral
      breast implants. Emergency chest tube thoracostomy resulted in rupture of one of
      the prostheses and caused subsequent migration of silicone into the chest cavity,
      where it led to empyema. The patient ultimately required a thoracotomy to
      evacuate the silicone and decorticate the lung. Review of the literature and
      methods to avoid this complication are described.

PMID- 8526645
TI  - Pedicled pericardial patch repair of a carinal bronchogenic cyst.
AB  - Bronchogenic cysts should be completely removed. Small communications with the
      tracheobronchial tree occur, but extensive involvement is rare. A case of
      bronchogenic cyst replacing the carina and the medial wall of the right and left
      main bronchi is presented. Resection and reconstruction was accomplished by using
      a pedicled pericardial patch to close the defect created by removal of the
      bronchogenic cyst. Follow-up at 2 years shows an excellent result.

PMID- 8526646
TI  - Synchronous reconstruction of the trachea and innominate artery in thyroid
      carcinoma.
AB  - A 50-year-old woman underwent combined resection and reconstruction of the
      trachea and the innominate artery synchronously for thyroid carcinoma. The
      pedicled thymus was interposed between the anastomosis of the trachea and the
      artery. The postoperative course was satisfactory. Synchronous reconstruction of
      the artery and trachea may thus prove to be safe, and interposition of the thymus
      flap may be useful in the prevention of secondary graft infection from the
      tracheal anastomosis.

PMID- 8526647
TI  - Aneurysm of the left pulmonary artery: surgical allograft repair.
AB  - We present a case of left pulmonary artery aneurysm with pulmonary valve
      stenosis. The aneurysm was excluded and the valve replaced by the implantation of
      a pulmonary artery allograft. The short-term follow-up (20 months) is promising.

PMID- 8526648
TI  - Cardiac transplantation for hypertrophic cardiomyopathy associated with Sengers
      syndrome.
AB  - Sengers' syndrome is a rare condition consisting of congenital cataracts,
      mitochondrial myopathy, and hypertrophic cardiomyopathy. The syndrome is
      transmitted in an autosomal recessive pattern. Progressive cardiac failure is the
      cause of death in most patients. This report describes cardiac transplantation
      for the treatment of the cardiomyopathy associated with Sengers' syndrome.

PMID- 8526649
TI  - Simplified method of reinforced sternal closure.
AB  - A simplified method of reinforcement for closure of the precarious sternum is
      described. This method uses a longitudinal sternal wire on each side, which lies
      within the transverse wires when they are approximated. The longitudinal wires
      serve as impenetrable reinforcements for the sternal halves, resulting in tight,
      secure approximation and preventing the transverse wires from tearing through the
      bone. The technique has been found quick and extremely effective.

PMID- 8526650
TI  - New surgical technique for repair of ventricular septal perforation.
AB  - We describe a technique for repairing the ventricular septal perforation using
      porcine pericardium tailored in a conical shape. This technique may allow a good
      operating view and facilitate suturing to the left ventricular cavity.

PMID- 8526651
TI  - Biatrial inferior transseptal approach to the mitral valve.
AB  - The standard surgical approach to the mitral valve is via a longitudinal incision
      in the left atrium. This is applicable in the vast majority of patients. In cases
      of small left atrium with poor exposure the standard incision may be modified. We
      report a biatrial inferior transseptal approach that we have employed in 25
      patients over a 2-year period. The technique is simple to execute and is without
      risk to surrounding structures.

PMID- 8526652
TI  - Modified pulmonary autograft aortic root replacement: the sinus obliteration
      technique.
AB  - A modified technique of aortic root replacement with the pulmonary autograft is
      described with the purpose of eliminating native pulmonary artery tissue as a
      support structure for the autograft valve leaflets. Large coronary buttons are
      preserved to replace the native pulmonary sinuses completely, and the noncoronary
      aortic sinus is left in situ to externally buttress the noncoronary sinus of the
      pulmonary autograft.

PMID- 8526653
TI  - The first lung transplantation.
AB  - The first lung transplantation in a human occurred at the University of
      Mississippi Medical Center on June 11, 1963. I was privileged to participate in
      this historic event, and I am pleased to share my thoughts with the readership of
      The Annals of Thoracic Surgery.

PMID- 8526654
TI  - Osteogenesis imperfecta and cardiovascular diseases.
AB  - Aortic and mitral valvular insufficiency in patients with osteogenesis imperfecta
      result from an underlying defect in connective tissue formation. The surgical
      cases reported in the literature have included mechanical and bioprosthetic valve
      replacement as well as attempts at repair and reconstruction. Despite
      complications related to bleeding and tissue friability, acceptable results have
      been obtained. In this report, we describe aortic regurgitation secondary to
      osteogenesis imperfecta treated with homograft replacement. The unique
      cardiovascular complications of osteogenesis imperfecta and the available
      therapeutic options are discussed in light of the literature review.

PMID- 8526655
TI  - Traumatic rupture of diaphragm.
AB  - Traumatic diaphragmatic rupture remains a diagnostic challenge, and associated
      injuries determine the outcome in those diagnosed early, whereas that of latent
      cases is dependent on the consequence of the diaphragmatic rupture: namely, the
      diaphragmatic hernia. To analyze the clinical and radiologic features and the
      therapeutic implications, we reviewed 980 patients reported in the English
      language literature. This injury affects predominantly males (male:female = 4:1)
      in the third decade of life, and is often caused by blunt trauma (75%). There
      were 1,000 injuries, of which 685 (68.5%) were left-sided, 242 (24.2%) right
      sided, 15 (1.5%) bilateral, and 9 (0.9%) pericardial ruptures; 49 cases were
      unclassified. Chest (43.9%) and splenic (37.6%) trauma were the most common
      associated injuries. The diagnosis was made preoperatively in 43.5% of cases,
      whereas in 41.3% it was made at exploration or at autopsy and on the remaining
      14.6% of the cases the diagnosis was delayed. The mortality was 17% in those in
      whom acute diagnosis was made, and the majority of the morbidity in the group
      that underwent operation was due to pulmonary complications. Uniform diagnosis
      depends on a high index of suspicion, careful scrutiny of the chest roentgenogram
      in patients with thoracoabdominal or polytrauma, and meticulous inspection of the
      diaphragm when operating for concurrent injuries. Repeated evaluation for days
      after injury is necessary to discern injury in patients not requiring laparotomy.
      Acute diaphragmatic injuries are best approached through the abdomen, as more
      than 89% of patients with this injury have an associated intraabdominal injury.
      Patients with diaphragmatic rupture presenting in the latent phase have adhesion
      between the herniated abdominal and intrathoracic organs, and thus the rupture is
      best approached via a thoracotomy.

PMID- 8526656
TI  - Thoracic outlet syndromes.

PMID- 8526657
TI  - Comparative morbidity of mitral valve repair versus replacement for mitral
      regurgitation with and without coronary artery disease. 1988. Updated in 1995.

PMID- 8526658
TI  - Chest wall resection for Ewing's sarcoma of the rib: an unnecessary procedure.
      1988. Updated in 1995.
AB  - Approximately 10% of all cases of Ewing's sarcoma arise from a rib. Conventional
      management has included chest wall resection (3 or more ribs) and radiation
      therapy. These forms of therapy have led to complications such as scoliosis and
      local deformity. The addition of radiation therapy can result in damage to the
      lung and adjacent viscera and also potentiate pulmonary restrictive disease.
      Between 1971 and 1978, 9 patients were treated with surgery, radiation therapy,
      and combination chemotherapy (three- or four-drug regimen). Only 2 patients (22%)
      survive. Since 1979, 14 patients were entered into a new protocol consisting of
      sequential induction chemotherapy, followed by delayed surgical resection
      whenever feasible. Three patients had complete resection of their primary lesion
      at onset. Initially, 7 patients had either biopsy (N = 4) or incomplete chest
      wall resection N = 3). All 4 patients with biopsy only at diagnosis had excellent
      responses to induction chemotherapy, allowing delayed resection of the involved
      rib without chest wall resection. Overall, 12 of 14 patients (86%) treated since
      1979 survive, with only 2 receiving radiation therapy for residual disease in the
      primary rib site.

PMID- 8526659
TI  - Spontaneous pneumomediastinum after sneezing.

PMID- 8526660
TI  - Technique for finding the left anterior descending coronary artery.

PMID- 8526661
TI  - Novel surgical approach to neurogenic dumbbell tumors.

PMID- 8526662
TI  - Ductus arteriosus ligation without a tube thoracostomy.

PMID- 8526663
TI  - Insulin infusions and coronary artery bypass grafting.

PMID- 8526664
TI  - Anterolateral thoracotomy for mitral valve replacement.

PMID- 8526665
TI  - Evaluation of the hemodynamic performance of stentless porcine aortic valves.

PMID- 8526666
TI  - Anabolic hormones in cardiomyoplasty.

PMID- 8526667
TI  - Transverse approach to the femoral artery.

PMID- 8526668
TI  - Preparing your practice for change: thoracic surgery into the next decade.
      Symposium held September 24-25, 1994, Atlanta, Georgia.

PMID- 8526669
TI  - Keynote: the future is here.

PMID- 8526670
TI  - Solo or partnership.
AB  - Reassessment of the managed care environment and restructuring of our practice
      will be accomplished by transitional short-term actions while we institute our
      long-range plan. In the short term we must develop appropriate relationships with
      hospitals and medical groups that interrelate to our specialty, and develop a
      "love our enemy" philosophy. We must establish operating organizational units
      that will be competitive. Reassessment of our own practice, our unique skills,
      our inadequacies, our competition, and our performance through outcome studies is
      essential to retake positions weakened by loss of contract inclusion. Long-term
      strategy must develop insurance coverage in conjunction with our patients in such
      a way that the middleman is eliminated and the profit currently extracted by
      managed care is reinvested in patient care, research, and education. Whoever
      controls payment determines the quality of medicine and how it is delivered.

PMID- 8526671
TI  - Hospital-based group: ideal practice for the future?
AB  - The format for future cardiothoracic surgical practices includes the option of a
      hospital-based group where provider groups and the hospital share the
      responsibilities and obligations of clinical care and the cost of that care.
      Based on personal experience at the Cedars-Sinai Medical Center, Los Angeles,
      three separate contract relationships during our tenure have reflected the
      evolution of cardiothoracic surgeons' relationship to our patients and the
      hospital in which we work. Although other organizational modes may prove equally
      successful, the hospital-based group practice is a viable structure that supports
      the preservation of quality in the work performed. This relationship helps to
      maintain a steady volume of patients enabling research endeavors, which are
      primarily funded through practice incomes, to continue and it also provides a
      platform for networking with defined patient referrals, shared services, and
      bench-marking with other centers.

PMID- 8526672
TI  - University surgical group.
AB  - The medical marketplace and various forms of contracted care place academic
      medical centers at a potential disadvantage. Recruitment of patients and
      maintenance of the academic mission may at times have disparate agendas. The
      university surgeon traditionally has embraced patient care, education, research,
      and administration with relative ease. Major price constraints and new forms of
      market competition now threaten the centralization of technology, the creativity,
      and the educational mission of university surgical practices. The university must
      deal with this new order by being proactive and flexible in negotiation. Faculty
      should conduct their business among themselves and with outside entities under a
      practice plan. Business management and physicians must try vigorously to
      understand each other. Finally, universities should use their expertise to lead
      in clinical outcomes research. The ideal university practice must show leadership
      in technological advances, retain the scientific method, and produce useful
      precise outcomes analysis. The academic surgeon must help solve problems
      involving excessive costs, assaults on creativity, and the business-medical
      interface. Time management will be essential.

PMID- 8526673
TI  - Integrated cardiac care.
AB  - In 1984 physicians at the Texas Heart Institute developed Cardiovascular Care
      Providers Inc, the first packaged-pricing plan for cardiovascular surgery. Under
      this arrangement, all services, including physician and hospital charges, are
      covered by a global payment package (bundled service). The resulting flat fee is
      lower than the sum of the individual charges. Since November 1984 the plan has
      been offered to the non-Medicare (less than 65 years old) population through
      contracts with self-insured corporations, prepaid health plans, union trusts, and
      foreign governments. In 1993 it was extended to Medicare patients who require
      coronary artery bypass grafting. Our experience has shown the plan lowers cost,
      increases patient access, allows payers to forecast their expenses, and
      streamlines the billing process, while maintaining a high quality of care and
      enabling patients to choose their own providers. Our success with this approach
      is attributed not only to the plan's simplicity, but also to the fact that it is
      physician directed and organ specific, involving many related specialties.
      Equally important keys to success include our hospital's large patient population
      and extensive database. Similar packaged-pricing plans have been adopted by
      several other cardiovascular centers. The approach is now being evaluated by
      Medicare in 6 other hospitals nationwide. With time, this approach is likely to
      become an increasingly popular reimbursement option.

PMID- 8526674
TI  - Mainstream vision for health reform.
AB  - The mainstream health reform bill of 1994 provides an excellent starting point
      for the health debate of 1995 and succeeding years. It is based on consumer
      choice, and the use of incentives to reward cost-efficient and medically
      effective practice. Only by solving this problem of efficiency first can we hope
      to make progress on the problem of equity--the broadening of access.

PMID- 8526675
TI  - Are cost considerations contradictory to quality?

PMID- 8526676
TI  - Managed care contracting/capitation.
AB  - Both the general approach for entering into a managed care contract and the
      subject of capitation are presented. The general approach section outlines the
      criteria that a physician group should apply in analyzing the feasibility of
      entering into a managed care contract with any insurer. The physician group's
      contracting process should be iterative and refined over time. The capitation
      section addresses issues revolving around the assessment of a capitated contract.
      The example assumes a typical health maintenance organization-primary care group
      contract. Not analyzed in this article are the exciting opportunities presented
      through specialty carveout capitation. Managing the transition to a more
      competitive environment will be the major challenge facing group practices.
      Survival in the tightening healthcare market will depend on sound strategic
      decisions regarding the physician group's mission as well as its relationship to
      its hospital partners and other delivery systems. To support these strategic
      decisions, a solid knowledge base and a thorough understanding of the terms and
      provisions regarding the formulation of these new relationships are necessary.
      The budget methodology is a relatively straightforward approach to establishing a
      capitation. Careful consideration will have to be given to the method of
      allocating the capitation among providers. A special concern is the risk-sharing
      arrangement with primary care physicians.

PMID- 8526677
TI  - You are in charge of cost.
AB  - Shifts in medical reimbursement dictate that physicians become knowledgeable
      about resource consumption. Price drives cost. The patient is now a cost center.
      Various models of physician-hospital integration are presented. A completely
      integrated staff in the hospital has the greatest potential for economic
      efficiency. The best method of cost accounting will include activity-based costs
      in a format that is understandable for physician education. Hospital cost
      management involves human resources, ordering practices, length of stay,
      purchasing, capital requirements, and benchmark targets. As health reform takes
      shape, physicians should be fully cognizant of cost, understand healthcare
      issues, and commit to improving the environment in which they practice medicine.
      The purpose of these activities is to improve the value of healthcare delivery
      for all patients.

PMID- 8526678
TI  - Quality initiatives and the power of the database: what they are and how they
      run.
AB  - The criteria by which healthcare is judged or measured are quality,
      accessibility, and cost effectiveness. To evaluate these criteria it is important
      to have a database. There are many strengths and weakness to large databases.
      They can be used as an indicator of the level of performance or quality, for
      clinical decision making, and as a measurement of cost effectiveness. They can
      also be useful in the evaluation and development of treatment algorithms and
      critical pathways for patients with entry level disease. In addition, they can
      measure patient access to healthcare and the appropriateness of care. It is
      important for these databases to appropriately adjust for preoperative risk
      factors that may influence outcome. Outcome in most of the databases is measured
      by mortality, but morbidity, functional status, quality of life, cost of care,
      length of stay, return to work, and patient satisfaction are also important
      outcomes. Factors that can influence the quality of the outcome data are the
      methods by which the data are collected, standardization of definitions, the
      currentness of the database, adequate numbers of patients and outcomes, and
      appropriate analytic techniques. It is important to feed back the data to the
      healthcare providers in a timely enough fashion so that processes and structures
      of care can be modified to improve treatment and results. The reliability of the
      databases and the validity must be substantiated for the healthcare provider to
      have confidence in the database.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526679
TI  - Optimizing cardiothoracic surgery information for a managed care environment.
AB  - The rapid change occurring in American healthcare is a direct response to rising
      costs. Managed care is the fastest growing model that attempts to control
      escalating costs through limitations in patient choice, the active use of
      guidelines, and placing providers at risk. Managed care is an information
      intensive system, and those providers who use information effectively will be at
      an advantage in the competitive healthcare marketplace. There are five classes of
      information that providers must collect to be competitive in a managed care
      environment: patient satisfaction, medical outcomes, continuous quality
      improvement, quality of the decision, and financial data. Each of these should be
      actively used in marketing, assuring the quality of patient care, and maintaining
      financial stability. Although changes in our healthcare system are occurring
      rapidly, we need to respond to the marketplace to maintain our viability, but as
      physicians, we have the singular obligation to maintain the supremacy of the
      individual patient and the physician-patient relationship.

PMID- 8526680
TI  - Quality initiatives and the power of the database: where we stand.
AB  - Many efforts to improve the quality of care focus on information drawn from
      databases. Such information can be very useful; however, the acquisition and
      analysis of data must be undertaken with caution. Six issues related to quality
      of care and the acquisition and analysis of data that pose problems for thoracic
      surgeons are the limitations and dangers of the right to know, the inadequacy of
      current databases, outcomes analysis and whether they help or hurt us, increased
      scrutiny of our practices, practice guidelines and the standards of care, and
      credentialing. To maximize the benefits of databases, physicians must participate
      in the process of data acquisition and analysis and the formation of practice
      guidelines. Speaking out against the misuse of incomplete or inaccurate data and
      supporting Society initiatives that address these concerns will help us as we
      strive to maintain a strong physician-patient relationship and to deliver optimal
      care to our patients.

PMID- 8526681
TI  - Think before you prep: defining the terms of change in American healthcare.
AB  - United States physicians are grappling with a fundamental reorganization of the
      healthcare system. Although many remain skeptical of governmental efforts at
      reform, they seem to take as given an industrial efficiency model of change,
      including large and integrated managed care arrangements and performance
      measurement based on outcomes such as quality. This uncharacteristic acquiescence
      seems to derive in part from a confounding of concepts. This article makes three
      distinctions: among knowledge about practice, knowledge about quality, and
      outcomes research; between outcomes research and the outcomes movement; and
      between the outcomes movement and other options for healthcare reform. The
      suggestion that statistical measurement of specific variables ought not to have a
      priori precedence over other ways of thinking--and doing something--about
      healthcare is made.

PMID- 8526682
TI  - Medical device industry efforts to increase healthcare value.
AB  - Although governmental healthcare reform initiatives have come to a stop in
      Washington, DC, the healthcare delivery system is, nevertheless, being
      transformed. Change is being driven by managed care organizations, which are
      looking for increased cost-effectiveness, and by providers of care and suppliers
      of medical products, who are trying to differentiate themselves from their
      competitors on the basis of service and quality. The efforts of one medical
      device company, Medtronic, are indicative of what the medical device industry is
      doing to increase the value (cost and quality) of healthcare.

PMID- 8526683
TI  - Industry's efforts: devices and pharmaceuticals.
AB  - The pharmaceutical industry has been irreversibly affected by the changes
      occurring in healthcare. Despite the obvious contributions of pharmaceuticals to
      human health, our customers are demanding that we help the patient and contribute
      to value, whether it be in terms of cost, clinical outcomes, or quality of life.
      We are learning to balance the variables to ensure that cost plus quality equals
      value in the marketplace in three ways: by focusing on the needs of the customers
      and demonstrating value through outcomes research, by maintaining an emphasis on
      innovation, and by taking an active role in the public arena to direct the course
      of our future. Outcomes research proves the value of what we do. Economic data
      will have to be correlated with clinical data. In addition to standard clinical
      and economic parameters, we must also provide quality of life data. Collaboration
      between the academic and the practicing community produces a win-win situation
      for both parties. Industry and practitioners are bonded together ineluctably in
      the service of the patient. Working together we can shape our future and the
      future of our patients.

PMID- 8526684
TI  - A physician workforce for the 21st century.
AB  - Medicine is entering an unprecedented era of provider abundance, including both
      physician and nonphysician providers. Over the next several decades, the
      projected number of primary care physicians will be more than adequate to meet
      national needs, although there is no assurance that any number of physicians will
      create an equitable distribution. At the same time, a growing surplus of
      specialists is projected. A balanced abundance in both primary care and specialty
      medicine will continue if approximately 33% of first-year residents ultimately
      practice primary care and 67% become specialists. In contrast, a shift to 50:50,
      as has been proposed by the Committee on Graduate Medical Education and others,
      will lead to a superabundance in primary care and a potential deficiency in
      specialty medicine later in the 21st century. Under either scenario, maintaining
      balance will be aided by those physicians with sufficient generalist skills to
      enable them to practice at the interface of primary care and specialty medicine,
      the domain of "middle care." The nation will be well served by educational policy
      that imparts such generalist expertise to medical students and that creates a
      workforce of highly skilled physicians capable of caring for patients in the
      technologically advanced clinical environment of the future.

PMID- 8526685
TI  - International perspectives: USA/Hawaii.
AB  - Most of the factors that underlie Hawaii's current healthcare system were in
      place by 1950. Many of its healthcare features were shaped during the period from
      the eighth century AD until the revolution in 1893. Early chiefs made care
      available for the entire population through specially trained kahunas, or
      priests, who specialized in healing. There was a uniform, seamless healthcare
      system. The historical legacy, which came through from the early days, fostered
      the existence and acceptance of group and salaried practice by physicians,
      acceptance by employers of the responsibility to provide healthcare to workers,
      capitated payments to providers, focus on outpatient services, and historically
      short hospital lengths of stay. The success of Hawaii's system is rooted in its
      past. Whether other states could or should adopt Hawaii's system is conjectural.
      In Hawaii healthcare reform is not a new paradigm but rather an evolutionary
      phenomenon.

PMID- 8526686
TI  - Overview: the next step.
AB  - If we are going to reform our healthcare system, we will have to start by
      providing access to basic care for everyone. This can be done through embracing a
      strategy that is built around integrated healthcare delivery systems. Payment
      should be via a universal tax for the basic plan, and there should be ways in
      which to pursue options beyond the basic plan, to be paid for by individuals.
      What is provided by way of care will need to be evaluated through a central
      technology assessment institute. The system will have to slow the rate of growth
      of spending in an intelligent way, not using price controls, caps, or repressive
      methodologies. The trick will be to still preserve a certain amount of freedom
      and flexibility, and include the capacity for change. There will have to be a
      significant reorientation of what has been our traditional approach to
      malpractice. Through the course of this symposium there has not been a great deal
      to be positive about. There are many physicians today who are well described by
      the English poet A. E. Housman's line, "A stranger and afraid in a world I never
      made." Change is inevitable; it is here and more is coming. The great medical
      historian Henry Sigerist noted that: "The physician's position in society, the
      task assigned to him, and the rules of conduct imposed on him changed in every
      period. They were determined primarily by the social and economic structure of
      society and by the technical and scientific means available to medicine at the
      time."(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526687
TI  - The low frequency of futility in an adult intensive care unit setting.
AB  - BACKGROUND: It is widely assumed that "futile" treatment consumes significant
      health care resources. This is a prospective cohort study. SETTING: The setting
      was the medical intensive care unit of Ben Taub General Hospital, a large public
      hospital in Houston, Tex. OBJECTIVE: To assess the frequency of intensive care
      unit patients meeting any of three broad definitions of futility. SUBJECTS:
      Subjects consisted of 129 consecutive patients admitted to the study intensive
      care unit during a 6-week period in the fall of 1993. MAIN OUTCOME MEASURES:
      Operational definitions for three types of futility described in the literature
      were developed: Imminent demise futility, death imminent regardless of
      intervention, was assessed by using the APACHE II (Acute Physiology and Chronic
      Health Evaluation II) scoring system to determine the likelihood of mortality at
      more than the 90%, 95%, and 99% probabilities. Lethal condition futility,
      conditions incompatible with long-term survival, included five separate disease
      processes. Qualitative futility, conditions with an unacceptable quality of life,
      was assessed as a persistent vegetative state or as meeting criteria for poor
      prognosis due to a hypoxic ischemic coma. RESULTS: Only 2 bed-days (0.3%) were
      used by patients with more than 90% predicted mortality; 22 bed-days (3.6%) were
      used by patients with poor prognosis due to hypoxic ischemic coma; and 101 bed
      days (16.4%) were used by patients satisfying criteria for the five lethal
      conditions. CONCLUSIONS: The frequency of futile interventions appears to be low
      unless one is willing to accept a definition that includes patients who could
      survive for many months. If confirmed in other settings, this suggests that
      concepts of futility will not play a major role in costs containment.

PMID- 8526688
TI  - Inappropriate thyroid gland ablation in patients with generalized resistance to
      thyroid hormone. A common sequela of a rare disorder.
AB  - Generalized resistance to thyroid hormone is one of several rare disorders of
      thyroid metabolism that can be associated with confusing symptoms and signs. Five
      cases of generalized resistance to thyroid hormone that were misdiagnosed with
      thyrotoxicosis, leading to unnecessary thyroid gland ablation and iatrogenic
      hypothyroidism, are reviewed herein. These cases illustrate the point that a
      careful review of the history, physical examination, and laboratory data, as well
      as an understanding of hormonal feedback relationships, will greatly benefit the
      practitioner in evaluating the patients with thyroid dysfunction. Consultation
      with an endocrinologist may be helpful to establish the correct diagnosis and
      avoid unnecessary treatments.

PMID- 8526689
TI  - The costs of antihypertensive therapy.

PMID- 8526690
TI  - Uncomplicate the treatment of uncomplicated urinary tract infections.

PMID- 8526691
TI  - Comprehensive geriatric assessment. Where do we go from here?

PMID- 8526692
TI  - US physician manpower needs. Generalists and specialists: achieving the balance.

PMID- 8526693
TI  - Protocol for writing cause-of-death statements for deaths due to natural causes.
AB  - The purpose of this article is to describe a protocol that provides suggestions
      and guides the clinical practice of writing cause-of-death statements for death
      certificates, autopsy reports, and other medical documents. The 16 members of the
      Autopsy Committee of the College of American Pathologists (CAP), Northfield, Ill,
      were appointed by the CAP officers based on demonstrated interest and expertise
      in autopsy performance and reporting. The committee perceived a need for specific
      instructions aimed at promoting consistency, accuracy, and completeness when
      writing cause-of-death statements. Development of a protocol was supported by CAP
      after approval by the CAP board of governors. The framework for the protocol was
      based on recommendations of the National Center for Health Statistics,
      Hyattsville, Md, with additional concepts added by the autopsy committee. The
      protocol for writing cause-of-death statements for natural causes is expected to
      foster consistency, accuracy, and completeness in the writing of cause-of-death
      statements. The quality of individual death certificates, autopsy reports, and
      national mortality data may improve through protocol usage. Application of the
      protocol principles should impose no ongoing costs at any user level because no
      new products or personnel are required for its application.

PMID- 8526694
TI  - Pathogenesis and treatment of the adult respiratory distress syndrome.
AB  - The adult respiratory distress syndrome is an acute clinical illness
      characterized by noncardiogenic pulmonary edema and refractory hypoxemia. Injury
      to the alveolar-capillary barrier and lung inflammation lead to intrapulmonary
      shunting of blood, surfactant depletion, and pulmonary vascular obstruction.
      Numerous mediators contribute to the pathologic response. Conventional therapy
      includes treating underlying causes and positive pressure mechanical ventilation.
      Concern about pressure-induced lung injury had led to new strategies to
      accomplish adequate gas exchange. Novel therapeutic interventions have included
      extracorporeal support techniques, use of compounds designed to neutralize
      proinflammatory cytokines, and administration of surfactants, but these efforts
      have not definitely affected mortality in randomized trials. Potent antioxidant
      agents have shown promise in animal models of acute lung injury, but human
      studies are lacking. Inhaled nitric oxide appears to have temporary effects on
      pulmonary artery pressure and on ventilation or perfusion relationships, but
      longer-term efficacy and safety in patients suffering from adult respiratory
      distress syndrome is unknown and awaits results of ongoing clinical trials.

PMID- 8526695
TI  - Evaluation of the patient with 'rule out myocardial infarction'.
AB  - Evaluation in the emergency department of the patient with chest pain remains a
      common problem. Large numbers of patients are admitted to the hospital because of
      diagnostic uncertainty. Strategies dealing with this population include risk
      stratification by clinical presentation, serial cardiac enzyme assays to exclude
      myocardial infarction, and detection of myocardial ischemia with nuclear
      scintigraphy or echocardiography. Each of these strategies is rational with
      specific benefits and weaknesses. Bypassing these steps and performing immediate
      exercise testing is the newest approach that appears to be safe, timely, and cost
      effective.

PMID- 8526696
TI  - The efficacy of intravenous amiodarone for the conversion of chronic atrial
      fibrillation. Amiodarone vs quinidine for conversion of atrial fibrillation.
AB  - BACKGROUND: Chronic atrial fibrillation (CAF) is a serious condition with
      significant morbidity and mortality. The mainstay of drug therapy for the
      conversion of atrial fibrillation to sinus rhythm continues to be quinidine. The
      value and safety of intravenously (i.v.) administered amiodarone therapy vs
      quinidine sulfate therapy was compared in a cohort of patients with CAF of more
      than 3 weeks' duration. OBJECTIVES: To evaluate the efficacy of i.v. administered
      amiodarone and oral quinidine sulfate containing 300 mg of quinidine in the
      conversion of CAF and to assess the effect of oral amiodarone in the conversion
      of CAF in the patients in whom CAF did not convert with IV amiodarone. METHODS:
      Thirty-two patients with CAF of more than 3 weeks' duration were randomized to
      either i.v. amiodarone treatment or oral digoxin/quinidine treatment in a
      randomized unblinded single crossover study. The converters continued either oral
      amiodarone therapy or quinidine extended-action tablet (Quinidex) therapy.
      RESULTS: Seventeen patients were randomized to the quinidine group and 15
      patients to the amiodarone group. Nonconverters from the quinidine group crossed
      over to the amiodarone group. Amiodarone and quinidine were equally effective at
      24 hours in converting CAF (eight [47%] of 17 patients in the quinidine group vs
      12 [44%] of 27 patients in the amiodarone group; P, not significant). At 2 and 9
      months of oral therapy, amiodarone was superior to quinidine in maintaining sinus
      rhythm. Only two of eight patients in the quinidine group tolerated the
      medication. All patients in the amiodarone group tolerated the medication. One
      additional patient converted to sinus rhythm at 2 months (13 [48%] of 27), and
      five more patients converted at 9 months (18 [67%] of 27). Amiodarone therapy and
      digoxin/quinidine therapy were equally effective at 48 hours in controlling
      ventricular response at rest. CONCLUSIONS: During the first 48 hours of
      treatment, i.v. amiodarone and oral quinidine were equally effective in
      converting CAF to sinus rhythm. At 2 and 9 months of therapy, treatment with oral
      amiodarone was superior to that of quinidine in restoring sinus rhythm. Long-term
      treatment with oral amiodarone is better tolerated than with quinidine.

PMID- 8526697
TI  - The impact of clinical trials on the use of medications for acute myocardial
      infarction. Results of a community-based study.
AB  - BACKGROUND: The impact of clinical trials on medical practice remains
      controversial, in part because of weak study designs and nonrepresentative study
      samples. OBJECTIVE: To assess changes in trends in medication use in the setting
      of acute myocardial infarction (AMI) before and after publication of two large
      clinical trials: the Second International Study of Infarct Survival (ISIS-2)
      trial that supported the use of aspirin after AMI and the Multi-center Diltiazem
      Postinfarction Trial that reported no overall benefit from the use of calcium
      antagonists after AMI. METHODS: Study patients consisted of 2114 patients
      hospitalized with AMI in 16 hospitals in metropolitan Worcester, Mass, during
      1986, 1988, and 1990. Data were obtained from medical records. We used
      multivariable logistic regression models to examine the rate of change in the use
      of selected medications before and after trial publication, controlling for
      medical history, characteristics and complications of AMI, medications taken, and
      procedures performed during hospitalization. The dependent variable was receipt
      of the specific medication under investigation. RESULTS: Before publication of
      ISIS-2, 26% of patients with AMI received aspirin while hospitalized compared
      with 66% after its publication. However, in-hospital aspirin use began to rise
      before ISIS-2 with an immediate increase in the level of use occurring after
      trial publication but with no significant change in the rate of increase. Before
      publication of the Multicenter Diltiazem Postinfarction Trial, 57% of patients
      with AMI were new recipients of calcium antagonists compared with 51% after trial
      publication. The decrease in calcium antagonist use began after trial publication
      (odds ratio, 0.79 per 6-month period; 95% confidence interval, 0.71 to 0.88).
      CONCLUSIONS: The published results of large trials of cardiovascular therapies
      have had variable impact on medication use. Efforts to assess the effects of
      publication of new scientific information on medical care need to consider prior
      trends in treatment patterns and the varying contexts of medical care. They
      should consider both direct and indirect routes of influence.

PMID- 8526698
TI  - Effect of potassium supplementation on blood pressure in African Americans on a
      low-potassium diet. A randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine the effect of potassium supplementation on blood pressure
      in African Americans consuming a low-potassium diet. DESIGN: Randomized, double
      blind, placebo-controlled trial with two parallel arms. SETTING: Community-based
      research site. PARTICIPANTS: Eighty-seven healthy African Americans aged 27 to 65
      years with a systolic blood pressure between 100 and 159 mm Hg and a diastolic
      blood pressure between 70 and 94 mm Hg. INTERVENTION: During the 21-day
      intervention period, all participants were provided with a low-potassium diet (32
      to 35 mmol/d). In addition to this diet, they were randomly assigned to receive
      either potassium supplements (80 mmol/d) or placebo. MAIN OUTCOME MEASURE: Change
      in blood pressure in the potassium vs the placebo group, based on a total of nine
      blood pressure readings at three visits. Blood pressures were taken before and
      during the intervention by means of random-zero sphygmomanometry. RESULTS: At
      baseline, the placebo and potassium groups were similar for mean blood pressure
      (127/78 vs 125/77 mm Hg), 24-hour urinary potassium excretion (50 vs 44 mmol),
      and all other variables measured (all P > .05). During the intervention, the net
      difference in 24-hour urinary potassium excretion between groups was 70 mmol.
      Compared with the placebo group, the potassium supplementation group experienced
      a net decline in systolic blood pressure of 6.9 mm Hg (95% confidence interval, 
      9.3 to -4.4 mm Hg; P < .001) and a decline in diastolic blood pressure of 2.5 mm
      Hg (95% confidence interval, -4.3 to -0.8 mm Hg; P = .004). Simultaneous
      adjustment for differences in baseline characteristics only strengthened these
      estimates. CONCLUSIONS: Potassium supplementation reduces blood pressure
      substantially in African Americans consuming a diet low in potassium. Increased
      potassium intake may play an important role in reducing blood pressure in this
      population at high risk for hypertension.

PMID- 8526699
TI  - Cost-effectiveness of pulmonary embolism diagnosis.
AB  - BACKGROUND: In recent years, improvements in the methods of clinical trials and
      the use of objective tests to detect venous thrombosis have enhanced the
      clinician's ability to diagnose pulmonary embolism. OBJECTIVE: To perform a cost
      effectiveness analysis of the commonly recommended strategies for pulmonary
      embolism diagnosis and management. METHODS: Two criteria of effectiveness were
      used: correct identification of pulmonary embolism and correct identification of
      patients in whom treatment was unnecessary. The cost of each diagnostic
      alternative was defined as the direct cost of administering the diagnostic test
      plus the treatment cost associated with a positive test result. Data derived from
      a decision analysis published separately on 662 patients were used for this
      study. RESULTS: A strategy based on the use of ventilation-perfusion lung scans,
      serial impedance plethysmography, and pulmonary angiography was the most cost
      effective. It remained so under all possible variations within the sensitivity
      analysis. CONCLUSIONS: The strategy that requires pulmonary angiography in the
      fewest patients is a combination of ventilation-perfusion lung scans and serial
      impedance plethysmography. This strategy also proved to be the most cost
      effective.

PMID- 8526700
TI  - Postdischarge geriatric assessment of hospitalized frail elderly patients.
AB  - BACKGROUND: The diffusion of comprehensive geriatric assessment services has been
      rather limited in North America partly because of reimbursement and
      organizational constraints. OBJECTIVE: To evaluate the impact of a comprehensive
      geriatric assessment intervention for frail older patients that is started before
      hospital discharge and is continued at home. METHODS: Patients older than 65
      years were selected who had either unstable medical problems, recent functional
      limitations, or potentially reversible geriatric clinical problems. Patients (n =
      354) were randomly assigned to either the intervention group or a control group.
      Information on survival, readmissions, nursing home placement, medication use,
      and health status was collected at 30 and 60 days after hospital discharge.
      RESULTS: No differences were observed between the two treatment groups in
      survival, hospital readmission, or nursing home placement by 60 days. After
      adjustment for baseline characteristics, no significant differences were observed
      between the two groups on measures of physical functioning, social functioning,
      role limitations, health perceptions, pain, mental health, energy and/or fatigue,
      health change, or overall well-being. CONCLUSIONS: Although efficacy has been
      demonstrated for some forms of comprehensive geriatric assessment, the types of
      services that are easier to establish (inpatient consultation services and
      ambulatory assessment) have not been shown to improve outcomes. Our results
      indicate that outcomes are unaffected by a limited form of comprehensive
      geriatric assessment begun in the hospital and completed at home. Further efforts
      are needed to develop and to evaluate realistic approaches to comprehensive
      geriatric assessment.

PMID- 8526701
TI  - Contaminated stethoscopes revisited.
AB  - BACKGROUND: Because of their universal use by medical professionals, stethoscopes
      can be a source of nosocomial infections. OBJECTIVE: To determine the frequency
      of contamination of stethoscopes with bacteria and fungi. METHODS: Cultures were
      obtained from 200 stethoscopes from four area hospitals and outpatient clinics in
      Houston, Tex. The frequency of stethoscope contamination in different groups of
      hospital personnel and medical settings was determined. We also measured the
      frequency of antimicrobial resistance of the staphylococcal strains that were
      isolated. RESULTS: One hundred fifty-nine (80%) of the 200 stethoscopes surveyed
      were contaminated with microorganisms. The majority of organisms that were
      isolated were gram-positive bacteria, primarily Staphylococcus species. Fifty
      eight percent of the Staphylococcus species that were isolated, including four
      (17%) of 24 Staphylococcus aureus isolates, were resistant to methicillin.
      Physicians' stethoscopes were contaminated more often than those of other medical
      personnel groups (P = .02). Stethoscopes used only in designated areas were
      contaminated less frequently than stethoscopes belonging to individual medical
      personnel (P = .01). Although stethoscopes were contaminated in all areas,
      stethoscopes from the pediatric medical setting were contaminated less frequently
      than those from other hospital areas (P = .009). CONCLUSIONS: Stethoscope use may
      be important in the spread of infectious agents, including antimicrobial
      resistant strains, and strategies to reduce the contamination of stethoscopes
      should be developed. We recommend disinfection of stethoscopes or regular use of
      disposable stethoscope covers.

PMID- 8526702
TI  - The effect of age and comorbidity in the treatment of elderly women with
      nonmetastatic breast cancer.
AB  - BACKGROUND: Increasing age has most often been associated with less aggressive
      approaches to treatment of nonmetastatic breast cancer in elderly women even
      after controlling for stage of disease at diagnosis. OBJECTIVE: To examine the
      influence of patient age on the initial treatment for breast cancer received by
      elderly women while controlling for the effect of patient comorbidity. METHODS:
      Cancer registry records for a cohort of 2252 women aged 66 years or older who
      were diagnosed as having nonmetastatic, invasive breast cancer between 1984 and
      1989 and identified through the Virginia Cancer Registry were linked to Medicare
      Provider and Reimbursement data files. Multivariate models were used to assess
      the effects of age and comorbidity (as measured by the International
      Classification of Diseases, Ninth Edition, codes recorded on Medicare claims) on
      initial treatment approach while adjusting for stage of disease, race,
      residential location, marital status, and year of diagnosis. RESULTS: In baseline
      multivariable models, age was negatively associated with any surgical treatment,
      non-breast-conserving procedures, and radiotherapy following breast-conserving
      surgery. The odds of women aged 85 years and older receiving surgery were less
      than one third those of women aged 66 to 74 years (odds ratio, 0.31; 95%
      confidence interval, 0.16 to 0.60), while odds ratios across the same two age
      groups for nonbreast-conserving surgery and adjuvant radiotherapy were 0.55 (95%
      confidence interval, 33 to 92) and 0.03 (confidence interval, 0.01 to 0.13),
      respectively. With additional adjustment for aggregate comorbidity, odds ratio
      estimates in these same age-group comparisons were virtually unchanged at 0.31,
      0.56, and 0.04. CONCLUSION: Aggregate comorbidity measured by inpatient
      International Classification of Diseases, Ninth Edition, codes on Medicare
      inpatient hospital claims does not explain age-related patterns in the initial
      treatment of elderly patients with breast cancer.

PMID- 8526703
TI  - Leisure-time physical activity among US adults. Results from the Third National
      Health and Nutrition Examination Survey.
AB  - BACKGROUND: The prevalence of no leisure-time physical activity (LTPA) among US
      adults is estimated to be between 24% and 30%. Such information, however, usually
      does not include prevalence estimates for non-Hispanic blacks, Mexican Americans,
      and the elderly. OBJECTIVE: To assess the prevalence of participation in leisure
      time physical activity among US adults. METHODS: Between 1988 and 1991, 9488
      adults aged 20 years and older were interviewed in their home as part of the
      third National Health and Nutrition Examination Survey. A clinic examination in a
      mobile center was also included. Mexican Americans, non-Hispanic blacks, and the
      elderly were oversampled to produce reliable estimates for these groups.
      Questions were asked about the type and frequency of physically active hobbies,
      sports, and exercises. RESULTS: The prevalence of no LTPA for US adults aged 20
      years or older from 1988 through 1991 was 22%. The rate was higher in women (27%)
      than in men (17%). Mexican-American men (33%) and women (46%) and non-Hispanic
      black women (40%) had the highest rates of no LTPA. Participation in moderate to
      vigorous LTPA five or more times per week decreased with age, with the largest
      decreases observed among non-Hispanic black men and women. In almost all
      subpopulations, gardening and/or yard work and walking were stated as the two top
      LTPAs of choice. CONCLUSIONS: Many Americans are inactive or irregularly active
      during their leisure time. Rates of inactivity are greater for women, older
      persons, non-Hispanic blacks, and Mexican Americans. Intervention strategies
      meant to promote lifetime physical activities among all Americans represents a
      major health priority.

PMID- 8526704
TI  - [Drug prescription in the postinfarction period; results of the EPPI II (Study of
      Postinfarct Prescription). A French cooperative study].
AB  - An enquiry into drug prescription of patients discharged from hospital after
      myocardial infarction was carried out in 27 French hospital departments and
      included 430 patients. Each patient was prescribed an average of 3.9 drugs.
      Aspirin was the most widely prescribed drug (79.3%); this was followed by the
      betablockers (67.4%), long acting nitrate derivatives (42.3%) and calcium
      antagonists (35.1%). These results, though an improvement compared with those of
      an enquiry carried out 3 years ago, suggest that much prescription in the post
      infarction period is not consistent with our present knowledge.

PMID- 8526705
TI  - [Influence of post-infarction myocardial revascularization on the prevalence of
      delayed potentials].
AB  - It has been shown that the presence of ventricular late potentials is a
      predictive factor of ventricular tachycardia and sudden death after myocardial
      infarction. The value of thrombolysis in the reduction of the prevalence of
      ventricular late potentials is now well established. However, the effects of
      other modes of revascularisation is less well known and more controversial. The
      authors undertook a retrospective study of 139 consecutive patients undergoing
      coronary angiography after primary myocardial infarction. The presence of
      ventricular late potentials fulfilling two of the three usual criteria was sought
      after a revascularisation procedure. The overall prevalence of ventricular late
      potentials was 30.9%. This was not affected either by the site of infarction of
      by the single or multiple character of the coronary artery disease. In addition,
      the left ventricular ejection fraction was not significantly different in
      patients with positive ventricular late potentials compared with the others. On
      the other hand, revascularisation of the culprit lesion responsible for the
      infarction was strongly correlated with a lower incidence of ventricular late
      potentials (p < 10 (-5)). In particular, the different incidence of positive late
      potentials between the dilated (9.3%) and non-dilated group (49.2%) was
      statistically significant (p < 10 (-6)) without any correlation to the single or
      multiple character of the coronary disease. The authors discuss the different
      reports in the literature concerning the effects of angioplasty and coronary
      bypass surgery on the incidence of ventricular late potentials. Conclusion; the
      review of the literature shows that thrombolysis significantly reduces the
      incidence of late potentials after myocardial infarction and the present study
      suggests that angioplasty and coronary bypass surgery may also be effective.

PMID- 8526706
TI  - [Cardiac transplantation; results after 5 years].
AB  - After cardiac transplantation, long-term results were assessed in a group of 46
      patients who survived more than 5 years after surgery. They were the survivors
      (50%) of a group of 92 patients who underwent transplantation before January
      1990. On January 1995, mean follow-up was 82 +/- 14 months. Quality of life was
      estimated satisfactory (mean score 8.4 +/- 2); 60% of the patients were active;
      89% were class NYHA I or II. Nevertheless, several problems have been identified:
      rise in body weight for all, over 10 kg in 31%; hypertension, renal failure,
      considered to be severe (serum creatinine > 250 micrograms/l) in 26%, diabetes in
      13%, osteoarthropathy in 33%, cancer in 6%, and, above all, chronic alteration of
      the coronary arterial bed in 53% of the patients. These problems reflect the
      immunological conflict and complications of immuno-suppression.

PMID- 8526707
TI  - [Prognostic value of exercise gamma-angiography in coronary insufficiency].
AB  - The predictive value for cardiac events in stable coronary artery disease was
      analysed with resting and exercise radionuclide angiography and conventional
      exercise stress testing under medical therapy. The population comprised 93 men
      and 12 women, followed up for 1 to 8 years (mean 51 months). The patients were
      divided into two groups. Group I without cardiac events; Group II including
      spontaneous complications and myocardial revascularisations. The analysis was
      performed at 2 years and at the end of follow-up. At 2 years, 30 events (15
      spontaneous complications, 15 revascularisations) were observed, and at the end
      of follow-up, there were 61 uncomplicated outcomes and 44 cardiac events (22
      spontaneous complications, 22 revascularisations). Two independent prognostic
      factors distinguishing patients in Group I from those in Group II were identified
      at 2 years and at the end of the study: exercise EF and occurrence of exercise
      (on: chest pain on exercise) chest pain. Four parameters were significantly
      different between the two groups at 2 years: exercise EF, resting EF, difference
      between exercise-resting EF (all p < 0.005) and duration of exercise testing (p =
      0.04). The 3 radionuclide parameters remained different between the 2 groups as
      well as chest pain on exercise stress testing (p = 0.03) throughout the study.
      The predictive value of these parameters depended on the type of cardiac event.
      The exercise EF was the best predictive factor of cardiac death. Pain and ST
      depression on exercise ECG were the best predictive factors for myocardial
      revascularisation. In 12 patients undergoing myocardial revascularisation, the
      clearest improvement was observed in exercise EF (p = 0.01).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8526708
TI  - [Regression towards the mean and repeated echocardiographic measurements of the
      left ventricular mass].
AB  - The selection of a group of patients based on a high value of a clinical or
      biological parameter leads to the finding of a tendency to a reduction of this
      value when remeasured, known as "regression towards the mean". The amplitude of
      this phenomenon is greater when the selected subjects are far from normal values
      and the intra-individual variability of the parameter under consideration is very
      high. Measurement of left ventricular mass is very affected by this statistical
      phenomenon. The authors undertook a prospective study to analyse the components
      of variability of repeated echocardiographic measurements of left ventricular
      mass and to quantify the expected effect of regression towards the mean in the
      follow-up of patients with left ventricular hypertrophy. Twenty-five randomly
      chosen subjects underwent 2 echocardiographic examinations at 2 week intervals:
      at each visit, the patient had two recordings and each recording was measured
      twice by the same "blinded" operator. Variance analysis showed intra-individual
      variability represented 30% of total variability, comprising only 2% for the
      measurements and 28% for the recordings and the visits. The importance of
      regression towards the mean was calculated with respect to the initial value of
      the left ventricular mass index: for example, when the left ventricular mass
      index was 150 g/m2, a spontaneous regression of 18 g/m2 can be expected at the
      next measurement. This phenomenon should be taken into consideration in the
      interpretation of longitudinal echocardiographic studies.

PMID- 8526709
TI  - [Evaluation of the systematic use of wide lumen 6 French guiding catheters in
      conventional coronary angioplasty].
AB  - The aim of this study was to evaluate the results of systematic use of 6 French
      guiding catheters in conventional balloon coronary angioplasty without any
      restriction of indications apart from coronary lesions necessitating other
      techniques such as atherectomy. Therefore, after a learning period, 200
      consecutive procedures performed between November 1993 and June 1994 for the
      treatment of 234 lesions were analysed prospectively. Fifty-one patients had
      stable and 70 unstable angina. In 79 cases, the angioplasty was performed on the
      culprit lesion of a myocardial infarction. An angiographic success was obtained
      for 206 lesions or 88% of cases which increased to 95% after exclusion of
      attempted recanalisation. There were 3 cases of damage to the ostium and 7
      patients underwent implantation of a stent with the same catheter for occlusive
      or threatening dissection. There were 10 ischaemic complications (5%) (7 non-Q
      wave infarctions, 2 Q wave infarctions, 1 aorto-coronary bypass, no deaths) and 8
      local complications at the site of arterial catheterisation during the hospital
      period. These results demonstrate the feasibility of coronary angioplasty with
      wide lumen 6 French guiding catheters and show that they amy be used in first
      intention for all conventional balloon angioplasty procedures.

PMID- 8526710
TI  - [Radionuclide ejection fraction at rest and in exercise in chronic aortic
      insufficiency. Pre- and postoperative study in asymptomatic or paucisymptomatic
      patients].
AB  - Twenty patients (17 men and 3 women: average age 50 +/- 14 years) with
      asymptomatic or paucisymptomatic aortic regurgitation were studied to compare the
      values of radionuclide left ventricular ejection fraction (EF) at rest and on
      exercise before (1) and 6 +/- 1 months (2) and 5.7 +/- 1.1 years (3) after
      surgery. The resting EF was similar at all three examinations: 53 +/- 8 (1); 57
      +/- 8 (2); 55 +/- 16 (3). However, it increased significantly on exercise from 40
      +/- 10 (1) to 54 +/- 12 (2) (p < 0.001) and to 52 +/- 20 (3) (p = 0.036 versus
      1). In the 7 patients with resting EF greater than 55 before surgery, there was
      no postoperative improvement: 61 +/- 6 (1); 61 +/- 5 (2); 65 +/- 9 (3). However,
      the exercise EF increased from 44 +/- 13 (1) to 55 +/- 17 (2) and 69 +/- 11 (3)
      (p = 0.004 vs 1). In 13 patients with resting EF < 55%, the value increased in
      the early postoperative phase but not later: resting: 49 +/- 5 (1); 55 +/- 8 (2)
      (p = 0.04); 49 +/- 17 (3) (NS vs 1); effort: 38 +/- 7 (1); 54 +/- 10 (2) (p <
      0.001); 40 +/- 16 (3) (NS vs 1). Left ventricular systolic function only returns
      to normal and exercise after surgery in patients with resting preoperative EF >
      or = 55%, but nothing indicates that this normalisation is an absolute condition
      for a successful surgical result in aortic insufficiency in terms of survival and
      quality of life.

PMID- 8526711
TI  - [Transesophageal echocardiography in cardiac and paracardiac tumors. A
      multicenter study].
AB  - A multicentre study was undertaken to determine the diagnostic value of
      transoesophageal echocardiography (TOE) in tumours of the heart and pericardium.
      Forty-five cases were recensed: 24 myxomas, 1 fibroma, 1 hydatid cyst, 2
      lymphomas, 3 sarcomas, 1 pleuropericardial cyst, 1 branchogenic cyst and 12
      cardiac metastases. The diagnosis was made in all 45 cases by TOE but only in 35
      cases by conventional transthoracic echocardiography which failed to recognise 2
      myxomas, 1 hydatid cyst, 1 sarcoma, 2 paracardiac cysts and 4 cardiac metastases.
      The site of the tumour was identified 45 times by TOE compared with only 12 times
      by transthoracic echocardiography. However, the anatomical investigation of
      mediastinal tumours requires complementary computerised tomography. Moreover,
      TOE, like all other imaging techniques, is unable to predict the benign or
      malignant nature of the tumour, 1 leiomyosarcoma having been confused with a
      myxoma.

PMID- 8526712
TI  - [Automatic implantable defibrillators. Clinical experience apropos of 45
      patients].
AB  - The aim of this study was to analyse the efficacy and survival after implantation
      of an automatic cardioverter-defibrillator.. Forty-five patients including 37 men
      were followed up for 0 to 51 months. The indications were ventricular
      fibrillation with no curable cause (n = 27) and sustained resistant or poorly
      tolerated ventricular tachycardia (n = 17) when programmed ventricular pacing
      with antiarrhythmic therapy was not applicable or gave poor results. One patient
      was implanted with this device for torsades de pointes. The underlying cardiac
      disease was ischaemic in 34 cases, non-ischaemic in 8 cases, and 3 patients had
      no apparent cardiac disease. Twenty patients were implanted with an epicardial
      system (group I) and 25 patients with endocardial system (group II). In group II,
      there was one complete failure of implantation requiring the use of an epicardial
      system and 2 partial failures requiring an additional epicardial patch electrode.
      The perioperative mortality was 2/45 (4.4%), both cases being due to permanent
      arrhythmias. In 5 patients, the minimal effective energy of defibrillation was
      over 25 Joules at implantation, without any untoward consequences on the clinical
      outcome. Ten non-fatal complications were observed including two major problems
      (haemopericardium); there were two cases of late increase of the minimal
      effective energy of defibrillation requiring the addition of a subcutaneous
      patch. Twenty-four patient (53%) received at least one appropriate therapy; 14
      patients (36%) had at least one inappropriate shock during follow-up. During
      follow-up, 7 patients died, 6 of a cardiac cause and 3 of an arrhythmic
      problem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526713
TI  - [Early surgery in acute endocarditis complicated by cardiac insufficiency; the
      Moroccan experience].
AB  - The aim of this review of 20 cases was to identify the surgical indications in
      heart failure complicating the acute phase of left heart valve endocarditis, to
      determine the optimal timing of surgery and to evaluate the early and medium term
      postoperative prognosis. Between January 1985 and May 1990, 20 patients (14 men
      and 6 women with an average age of 29 +/- 7 years) with native left heart valve
      endocarditis underwent surgery in the acute phase complicated by heart failure.
      The were 9 aortic regurgitations and 2 mixed mitral and tricuspid regurgitations.
      The haemodynamic status of the patients was poor before surgery: 15 NYHA class IV
      and 5 class III. The average time from the onset of heart failure to surgery was
      21 days. The surgical procedure was monovalvular replacement in 14 cases, double
      valve replacement in 4 cases and 2 isolated mitral valvuloplasties. Two patients
      died in the first postoperative month of irreducible low output syndrome. One
      patient was reoperated early for dehiscence of a mechanical valve prosthesis.
      Late complications included 2 cerebrovascular accidents and one reoperation for
      degeneration of a bioprosthesis. There were no late fatalities. Seventeen of the
      18 survivors are regularly followed up with an average of 80 months follow-up: 12
      NYHA class I and 5 class II. The most useful prognostic factor was the
      preoperative haemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526714
TI  - [Heart valve surgery. A half-century history].

PMID- 8526715
TI  - [Recording of pulmonary venous flow with Doppler echocardiography; normal and
      pathological aspects].
AB  - The appearances of pulmonary venous flow Doppler echocardiography have been the
      subject of many reports. The recording is obtained by transthoracic or
      transoesophageal pulsed Doppler examination. The value of this parameter in the
      study of left ventricular diastolic function has been clearly established. The
      transoesophageal approach is mainly useful for quantifying mitral regurgitation
      and for monitoring left atrial pressure during surgery. This review of the
      literature describes the methods of recording and the normal appearances of
      pulmonary venous flow, and then discusses the different variations encountered in
      pathological conditions.

PMID- 8526716
TI  - [Myxoma of the mitral valve; apropos of 2 surgically treated cases. Review of the
      literature].
AB  - The authors report two cases of anterior mitral valve myxoma. This is an
      exceedingly rare localisation and these cases add to the other 8 previously
      reported cases. Intracardiac tumours and valvular endocarditis may be detected
      non-invasively by echocardiography but the precise diagnosis may be extremely
      difficult: mitral valve myxoma is an exceptionally rare condition. Treatment was
      surgical in both reported cases.

PMID- 8526717
TI  - [Cerebral abscess disclosing tetralogy of Fallot with situs inversus in
      adulthood].
AB  - The authors report the case of tetralogy of Fallot (TOF) associated with situs
      inversus, the first description of this rare association in a previously
      asymptomatic adult. A 32 years old chauffeur was admitted to hospital with
      pyrexia and convulsions due to a left temporo-parietal cerebral abscess which had
      a favourable outcome. The chest X-ray and Doppler echocardiographic study showed
      a TOF with a high infundibular stenosis and dextrocardia. Abdominal
      ultrasonography confirmed a complete situs inversus. The good tolerance was
      attributed to the equilibrated character of the TOF. The orientation of the heart
      and the cono-truncal septation occur at different times during embryogenesis.
      However, there are genetic arguments in favour of the non-fortuitous nature of
      this association.

PMID- 8526718
TI  - [Bipolar transseptal radiofrequency ablation of posteroseptal bundle of Kent.
      Apropos of a case].
AB  - The posteroseptal localisation of accessory pathways is sometimes responsible for
      important difficulties for radiofrequency current endocavitary ablation. Some
      authors have reported the exceptionally rare use of the transseptal bipolar mode
      for ablation of this type of accessory pathway. The authors report the case of a
      patient in whom failure of unipolar radiofrequency ablation at the tricuspid and
      then mitral annulus was followed by immediate success when the bipolar mode was
      used. The value of recording with the transseptal dipole at the ablation site is
      emphasised.

PMID- 8526719
TI  - Effects of dietary sulfur amino acids and crude protein on the performance of
      finishing broilers.
AB  - The effects of different combinations of dietary methionine + cystine (Met + Cys)
      and dietary crude protein (CP) in finishing broilers were investigated in two
      growth studies. In Exp. 1, male broilers 29 to 42 days of age were fed 18 diets
      containing 16.9%, 18.7%, or 20.4% CP with six levels of Met + Cys within each
      protein level. Similarly, in Exp. 2 another 12 diets containing either 18.0 or
      21.5% CP were fed to male broilers 29 to 48 days of age. In general, the Met +
      Cys requirement for optimum feed conversion was higher than for maximum growth.
      In both experiments, between 0.80% and 0.85% methionine + cystine optimized feed
      conversion. These dietary levels were valid for a 13.05 MJ ME/kg diet fed to
      broilers growing from 1.2 kg to 2.2 kg (Exp. 1), or for a 13.60 MJ ME/kg diet fed
      to broilers growing from 1.3 kg to 3.0 kg (Exp. 2). The Met + Cys requirement was
      not consistently affected by the dietary CP content in Exp. 1. In Exp. 2,
      increasing dietary CP from 18.0% to 21.5% tended to increase the Met + Cys
      requirement for optimum feed conversion. A dietary CP level of 18.0% to 18.7%
      supported performance and carcass fat deposition equal to diets containing 20.4%
      or 21.5% CP, respectively, when the sulfur amino acid content was adequate.

PMID- 8526720
TI  - Transformations and effects of lipids in the rumen: three decades of research at
      Gent University.
AB  - A survey is given of research results on ruminant lipid digestion obtained at the
      authors' laboratory. Results are presented in terms of lipid changes occurring in
      the rumen and in terms of effects on nature, extent and site of digestion. The
      rumen can be adapted to an extremely high capacity for triglyceride lipolysis,
      preferentially releasing polyunsaturated fatty acids that are then further
      hydrogenated with accumulation of oleic acid isomers in vitro only. Evidence was
      obtained for both microbial incorporation and synthesis of polyunsaturated acids.
      In vitro lipolysis is inhibited by pH values below 6.3 and by ionophores. Free
      fatty acids inhibit methanogenesis with associated increases in propionate
      production and decreases in acetate and butyrate productions; the latter being
      related to their defaunating effect. Both in the faunated and defaunated rumen,
      free fatty acids decrease fibre digestion, which is shifted to the hindgut, at
      least in sheep. Defaunation increases rumen microbial growth efficiency and may
      result in a higher duodenal flow of both feed and microbial protein, provided
      these increases are not overcome by a decreased apparent rumen OM digestibility.
      Considerable between animal variability exists for these effects, associated with
      variable effects on rumen particle and liquid volumes and outflow rates.

PMID- 8526721
TI  - Response of renal orotic acid and creatinine to treatments affecting metabolic
      protein supply of ruminants.
AB  - 90 urine samples obtained in three lamb trials and one experiment using adult
      wethers were analyzed for their contents of orotic acid and creatinine. The
      average daily excretion of orotic acid accounted for 0.5 mg to 1.5 mg (35
      micrograms to 130 micrograms/W0.75) with a high individual variation. Correlation
      coefficients between orotic acid and other urinary constituents were low
      indicating an entirely different response to metabolic variations. There was only
      a weak relationship to live weight, protein retention and rumen fluid traits.
      Defaunation reduced the orotic acid excretion (significant in the adult wethers)
      whereas the addition of rumen-protected lysine as well as the use of different
      dietary carbohydrate sources were without effect. The urinary excretion of
      creatinine increased with live weight and age from 0.4 g/d in the 20 kg lambs to
      1.7 g/d in the adult 53 kg wethers. The correlations with live weight were close
      whereas the apparently negative correlation with protein retention was not real
      as could be evaluated by calculation of the partial correlations. There was a
      close correlation of creatinine with total N, urea and allantoin. Neither
      defaunation nor rumen-protected lysine and the kind of carbohydrate source had
      significant effects on creatinine. The use of orotic acid and creatinine as
      indicators of metabolic disorders were discussed. Easy application in practical
      diagnosis without quantitative urine collection might be possible by the
      determination of orotic acid in the milk of cows and of the creatinine/N ratio in
      urine.

PMID- 8526722
TI  - [Evaluation of different markers for the determination of microbial nitrogen flow
      into the duodenum of dairy cows].
AB  - 2,6-Diaminopimelic acid (DAPA), ribonucleic acid (RNA), 15N, D-alanine (D-ALA)
      and the amino acid profiles (AAP) were compared as microbial markers for
      determination of the microbial protein synthesis in the rumen. Three dairy cows
      (Schwarzbuntes Milchrind, LW 602 kg), each fitted with a rumen cannula and a re
      entrant cannula in the proximal duodenum, were offered four isoenergetic and
      isonitrogenous diets (mean daily intake 15.0 +/- 0.45 kg DM; forage: concentrate
      = 50:50) in a periodic experiment. The diets contained soyabean extracted meal,
      meat and bone meal, pea meal and dried clover as major sources of protein. On the
      4th day after administration of 9 g 15N-labelled urea (95 atom-% 15N-excess) per
      day, samples of rumen fluid and duodenal digesta were obtained 3 h after feeding.
      The bacteria were isolated by differential centrifugation. Bacteria harvested
      from the rumen had significantly higher 15N enrichment and D-ALA: N ratio than
      'duodenal' bacteria. However, DAPA: N ratio was higher in 'duodenal' bacteria
      compared to rumen bacteria. There were no differences in RNA: N ratio between
      rumen and 'duodenal' bacteria. The source of the bacteria in the digestive tract
      has an influence on the ratio of microbial N: total N, especially when 15N, AAP,
      DAPA and D-ALA but not RNA were used as markers. The most reproducible method was
      D-ALA (C.V. 4.7 for rumen and 6.8 for 'duodenal' bacteria) followed by 15N (10.8
      resp. 4.8) and RNA (9.7 resp. 8.2). The results obtained with 15N and D-ALA
      agreed closely at the same source of bacteria. The RNA method reached the level
      of these markers (15N, D-ALA) when the bacteria were isolated from the duodenum.
      It is concluded that D-ALA (bacteria isolated from rumen and duodenum) and also
      15N (bacteria isolated from duodenum) were the best markers for estimation of the
      microbial protein synthesis.

PMID- 8526723
TI  - [Results from measurements of nitrogen and energy metabolism in adaptive
      different cattle].
AB  - In experiments with Galloway (G), Highland (H) and Black-White Dairy (B) cattle
      no significant differences between the breeds were measured in the energy and
      nutrient digestibility and energy metabolizability of rations with high variation
      in the nutrient composition. In H and B cattle no differences existed in
      digestibility in relation to the environmental temperature (30, 18 and 3 degrees
      C). Lowering the environmental temperature from 18 to 12 and 4-6 degrees C
      resulted in no changes of heat production in G and H but in B heat production
      increased about 6% and 20% respectively.

PMID- 8526724
TI  - [Digestibility of ungraded crude protein from the rumen and of treated protein
      feeds in the postruminal part of the digestive tracts of ruminants].
AB  - The effective degradability and intestinal digestibility of CP of untreated and
      with formaldehyde (F) treated sunflower press--cakes (SF), lucerne meal (LM) and
      field beans (FB) were measured on polycannulated bulls by "in sacco" and "mobile
      bag" methods. The feeds were treated by F solution in doses from 0.2; 0.4... to
      2.0 g F per 100 g CP. The effective CP degradability after treatment was
      decreased significantly (for SF from 78 to 33%, LM from 73 to 62%, FB from 70 to
      47% with max. dose of F). The effect of F was various on individual feeds. The
      intestinal digestibility of treated feeds, without previous incubation in the
      rumen, passed from abomasum to feces has been influenced with doses of F non
      significantly. The digestibility of FB treated with max. dose of F was lower
      about 20% in the part duodenum feces than in abdomasum feces. The digestibility
      in the part caecum--feces for all tested feeds has been decreasing with doses of
      F, similar as in the rumen. The intestinal digestibility of in rumen undegraded
      crude protein residues of SF has been influenced by the treatment positively. It
      increased from 43 to 82%. The effect of F on LM was very low. The digestibility
      has been changed from 75 to 80%.

PMID- 8526725
TI  - [Contents and deposition of major minerals in tissues and in the whole bodies of
      growing young bulls German Simmental breed].
AB  - 54 bulls of the German Simmental breed were fed either on a high energy level
      (maize silage ad libitum and 1.8 kg concentrate) or on a low energy level (maize
      silage restrictively and 1.0 kg concentrate). In dependence on feeding intensity
      a mean daily weight gain of 870 or 1210 g was obtained. Animals were slaughtered
      with a live mass of 200 kg, 350 kg, 500 kg, 575 kg and 650 kg. Empty body was
      divided into 13 cuts and afterwards separated into lean, bone and adipose tissues
      and tendons. Major mineral element content was determined in these tissues as
      well as in the noncarcass parts. In the lean tissue the mean content (200 kg) of
      0.3 g calcium, 10 g phosphorus, 1 g magnesium, 2.3 g sodium and 14.8 g
      potassium/kg dry matter decreased slightly with rising live mass (200-650 kg).
      The contents of major mineral elements were much higher in bone tissue. For the
      fattening period from 200 to 650 kg of live mass mean contents of 151.5 g
      calcium, 71.3 g phosphorus, 3.2 g magnesium, 5.1 g sodium and 1.1 g potassium per
      kg DM were analysed. Mineral element content of bone tissue increased with rising
      live mass as well as animals on low feeding intensity showed a higher mineral
      content than on high energy level. In all, major mineral element content in fat
      tissue was very low. In noncarcass parts head and legs calcium and phosphorus had
      analogous to bone tissue the highest concentration. Hide showed a high content of
      sodium, whereas organs and digestive tract had a high content of potassium and
      phosphorus. Total mass of major mineral elements in the different tissues
      increased above all in the fattening period of 200 to 350 kg. In carcass as well
      as in empty body, mass of calcium and phosphorus was much higher than magnesium,
      sodium and potassium. Also animals on low feeding intensity showed a higher mass
      of major mineral elements in carcass and empty body than animals on high energy
      feeding intensity. The intensively fed bulls had a mean deposition of 12.7 g
      calcium, 6.9 g phosphorus, 0.37 g magnesium, 1.2 g sodium and 2.1 g potassium per
      1000 g of empty body weight gain, whereas restrictively fed bulls deposited in
      average 15.0 g calcium, 7.8 g phosphorus, 0.4 g magnesium, 1.2 g sodium and 2.4 g
      potassium per 1000 g of empty body weight gain.

PMID- 8526726
TI  - [Investigations of empty body weight gain, on protein, fat and energy disposition
      as well as on utilization of metabolizable energy for energy deposition in black
      and white bulls. 1. Empty body weight gain].
AB  - Six series of individual feeding experiments (altogether 544 animals) with
      different energy supply and connected with steps slaughteries and whole-body
      analyses, constructed carried out and analysed upon the same aspects, were
      regression analytically interpreted with the aim of quantify the relation of
      empty body weight to live weight. The relation of empty body weight to live
      weight showed a nonlinear dependence on the live weight as well as on the age of
      animals. The assessment of the metabolizability of energy of the diet as an
      additional variable reduced the residual variation considerably. Therefore from
      the knowledge of live weight or age of the animals, and the metabolizability of
      energy of the diet the relation of empty body weight to live weight of black and
      white bulls could be calculated. Moreover, the relation of empty body weight gain
      to live weight gain in dependence on live weight and live weight gain was
      investigated.

PMID- 8526727
TI  - [Effect of a supplemental Aspergillus niger phytase on the utilization of plant
      phosphorus by rainbow trout (Oncorhynchus mykiss)].
AB  - Effects of a supplemental Aspergillus niger-phytase on digestibility and
      utilization of dietary phosphorus (P) were studied in three experiments with
      rainbow trout. P concentration in the diets was 4.8 and 5.8 g/kg DM,
      respectively. The P contained in the diet originated solely from plants, mainly
      soy-products. Digestibility of P was studied using the stripping method and
      hydrochloride insoluble ash as marker. Utilization was studied in growth trials
      by use of the comparative body analysis. At a water temperature of 15 degrees C,
      both digestibility and utilization of P were increased from 25 to 57% and from 17
      to 49%, respectively when 1000 U/kg phytase were supplemented. Feed consumption
      and gain of trout were significantly increased. At a water temperature of 10
      degrees C, utilization of P was also increased from 6 to 25%. However, feed
      consumption and gain of trout were very low at this water temperature and not
      influenced by the supplemental phytase.

PMID- 8526728
TI  - The effect of dietary energy and protein concentration and feeding level on feed
      utilization and body composition of carp (Cyprinus carpio L.).
AB  - A three factorial designed feeding experiment with common carp (Cyprinus carpio
      L.) was carried out in an intensive experimental rearing system. Fish (initial
      body weight 200 g) were fed on two different levels of dietary energy (16 and 18
      MJ DE/kg DM), two different levels of protein (320 and 420 g CP/kg DM) and also
      two different feeding intensities (100% and 75% of the maximum intake). The
      experiment was terminated when fish reached a mean body weight of 1300 g. Growth,
      feed utilization and nutrient composition of the whole body and fillet were
      observed. The highest growth was obtained when the fish were fed on the diet
      containing high dietary energy and high dietary protein with satiation feeding.
      High dietary energy, high dietary protein and restriction of feed intake improved
      feed conversion ratios. High dietary energy, low dietary protein and restrictive
      feeding increased energy utilization. Low dietary protein and restrictive feeding
      resulted in better protein utilization. Fish fed with high dietary energy
      contained more fat and less protein in their carcasses. A lower fat content but
      higher protein and higher ash content in fish carcasses was shown when fish were
      fed with a diet high in protein and fed restrictively.

PMID- 8526729
TI  - Nutritional value of protein hydrolysis products (oligopeptides and free amino
      acids) as a consequence of absorption and metabolism kinetics.
AB  - When pigs were submitted to duodenal infusion of solutions containing a large
      percentage of small peptides (PEP) or free amino acids with the same pattern
      (AAL) amino acids appear in the portal blood more rapidly and more uniformly
      after infusion of PEP then after infusion of AAL, with the notable exception of
      methionine for which the opposite was true. These differences were lowered when a
      carbohydrate (maltose dextrin) was present in the solution, but nevertheless
      remained significant for the first hour after the infusion. The long-term (8
      hour) uptake of free amino acids into the liver and the peripheral tissues
      differed in profile according to the nature of the duodenal infusion. Peripheral
      uptake was appreciably less well balanced after infusion of free amino acids
      (deficiency of threonine and phenylalanine) than after infusion of small peptides
      (deficiency of methionine). Accordingly, in the rat, under conditions of
      discontinuous enteral nutrition the mixture of small peptides was of greater
      nutritive value than the mixture of free amino acids. It thus appears that the
      absorption kinetics which results in important variations in the temporal
      distribution of free amino acids in the tissues may be at the origin of
      transitory imbalances in tissue amino acid uptake, and as a result of a lower
      nutritive value.

PMID- 8526730
TI  - [Time course of amino acid absorption in growing rats after feeding of a 15N
      labeled wheat/yeast ration].
AB  - The time course of AA digestion, AA balance (sV AS), and AA absorption (wV AS)
      was estimated on growing rats (Wistar rats, LW = 124 g) in different sections of
      the intestinal tract using the combination of 15N tracer and TiO2 marker
      techniques. The animals received once a diet of 15N labelled wheat and yeast as
      protein sources supplemented by TiO2 as a marker. Up to 6 h after feeding the
      amino acid composition the 15N excess and the TiO2 content in the digesta of
      stomach, small and large intestine were determinated in the relation of amino
      acids resp. of 15N labelled amino acids to the marker. In addition the content of
      amino acids and the 15N excess of these amino acids were estimated in plasma.
      From these data the disappearance rates and the relation of exogenous to
      endogenous amino acids as well as the sV and the wV values of the different amino
      acids were calculated for the different gut sections. The following results were
      obtained: The relative disappearance rate for N and TiO2 marker out of the
      stomach went approximately parallel but with a delay for TiO2 of about 30
      minutes. The AA composition of the stomach content, the small and the large
      intestine content did not vary in dependence of the time. The AA composition of
      the stomach digesta was nearly identical to that of the diet, while that of the
      small intestine was between exogenous AA composition (feed) and endogenous AA
      composition (digesta on protein free feeding). AA composition of the large
      intestine digesta showed quite big differences (bacterial AA break down and AA
      synthesis). Considering a delay time (small intestine: 1 h, large intestine: 4 h)
      the exogenous portion of the different AA remained constant in both of these
      intestinal sections during the whole experimental time. The exogenous AA part
      varied for small intestine digesta between 31 and 69% (mean value: 41%), and for
      large intestine digesta between 13 and 39% (mean value: 22%). The sV AS values in
      the small intestine (AA balance resp. precaecal digestibility) differed from 61%
      (threonine) to 86% (proline) with an average of 73.4 +/- 7.4%, those for wV AS
      (AA absorption) from 81% (lysine) to 94% (proline) with an average of 88.1 +/-
      4.1%. There were significant differences between AA, but they are negligible for
      practical purposes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8526731
TI  - Quantitative partition of protein, carbohydrate and fat pools in growing pigs.
AB  - A model combining data from balance experiments with data from oxidation of
      nutrients demonstrating the pools of protein, carbohydrate and fat and their
      partition in the body was presented. Data from more than 200 experiments with
      growing pigs were used to fill up the "black boxes" in the model and to discuss
      the pattern between catabolic and anabolic processes of the different nutrients.
      With a ME-intake of 1.3 MJ/kg0.75 the proportion of retained protein from the
      protein pool varied from 50 to 75% depending on the age of animals and the
      protein quality. At a low protein intake and ME of 0.6 MJ/kg0.75 the utilization
      of protein was reduced to about 25% as a substantial part of the protein pool was
      oxidized. The carbohydrate group from the protein sources constituted less than
      5% of the carbohydrate pool. The oxidation of carbohydrates was between 50-75% of
      the pool in all experiments, while the rest was used for lipogenesis. Even on a
      low feeding level the pattern occurred indicating a requirement for specific
      substances formed in the body. Lipogenesis constituted 46-96% of the fat pool
      depending of the amount on digested fat in the different experiments. No
      oxidation of fat was observed in experiments with pigs (30-90 kg LW) on a high
      feeding level in spite of the broad variation in the amount of digested fat,
      indicating a complete storage of the fat pool into body fat. In experiments with
      piglets (3-9 kg LW) on the same energy intake fat oxidation of about 30%
      occurred, probably caused by the high energy requirement of the piglets.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8526732
TI  - [Effect of avilamycin and tylosin on the metabolizable energy in growing and
      finishing pigs].
AB  - In two metabolism trials with growing and finishing pigs the influence of the
      antibiotic feed additives Avilamycin and Tylosin on the metabolizable energy was
      investigated at different levels of dietary protein content. In the first
      experiment (growing pigs) the antibiotics were supplied at levels of 0 mg/kg, 40
      mg/kg Avilamycin and 40 mg/kg Tylosin to diets containing 18.5%, 17.5%, 16.5% and
      14.0% of crude protein. In the second experiment (finishing pigs) 0 mg/kg
      antibiotics, 20 mg/kg Avilamycin and 20 mg/kg Tylosin were used in diets
      containing 16.5% and 14.0% of crude protein. The body weight of the animals
      averaged 46 kg (growing pigs) and 68 kg (finishing pigs). In growing pigs the
      supplementation of Tylosin increased the digestibility of dry matter and energy
      at 1 percentage unit each, while in finishing pigs no effects were observed.
      Since the urinary energy excretion was not affected by antibiotics, there was
      only in Tylosin treated growing pigs a slight rise in dietary contents of
      metabolizable energy by 1.6%. The reduction of the dietary protein content
      resulted in increased digestibility of dry matter and energy, reduced urinary
      energy excretions and increased dietary contents of metabolizable energy.

PMID- 8526733
TI  - [Chromium supplements in the feed for growing pigs and meat quality].
AB  - An experiment with 40 female growing pigs from 27.4 to 106.5 kg body weight (BW)
      in individual pens was conducted to evaluate the effect of different chromium
      supplements (Cr-chloride, Cr-yeast and Cr-picolinate) according to 0.5 ppm Cr in
      the diet compared with a control diet without any additional chromium. The
      influence on growth performance and carcass as well as meat composition was
      studied. In comparison with the control diet body weight gain and feed conversion
      ratio in the finishing period (60 to 106.5 kg BW) were significant increased and
      lowered respectively in the treatment with Cr-chloride and with the other Cr
      supplements tendentially. The results of the carcass composition as well as the
      fatty acid profile of neutral and complex lipids in the muscle (M. longissimus
      dorsi) at the 10th rib did not indicate a statistically significant effect of the
      Cr supplements. Furthermore energy utilization on the base of digestibility was
      not affected. Concerning the Longissimus muscle area and the intramuscular fat
      content there were positive tendencies of the investigated Cr supplements.

PMID- 8526734
TI  - [Effect of ethoxyquin on the utilization of selenium in growing pigs].
AB  - In a 2 x 3 factorial arrangement with 30 male castrates (German Landrace; 13.7 +/
      1.7 kg b.w.), after a 2 week feeding period with a maize/torula yeast basal diet
      poor in selenium and without vitamin E supplementation, the effect of two
      ethoxiquin concentrations (0 and 150 mg/kg) und 3 selenium concentrations (0.075,
      0.10 and 0.125 mg/kg) on growth, the activity of the Se dependent GSH-Px in the
      erythrocytes and the Se concentrations in liver, kidney, heart and diaphragm was
      measured after 4 weeks on the experimental diets. Under the experimental
      conditions chosen ethoxiquin had no effect of any of the parameters studied.
      Selenium supplementation significantly increased the enzyme activity and the Se
      concentrations in the organs and tissues analyzed.

PMID- 8526735
TI  - The influence of dietary fibre on protein digestion and utilization in
      monogastrics.
AB  - Current knowledge of the effects of dietary fibre and associated components on
      protein digestibility and utilization are discussed. Based on the literature it
      could be shown that the implications and mechanisms behind the effect of soluble
      and insoluble dietary fibre on protein digestibility and utilization are quite
      different. Insoluble dietary fibre will increase faecal bulk and faecal nitrogen
      excretion is primarily due to and increased excretion of cell wall bound protein.
      Contrary to this, soluble dietary fibre increase faecal bulk and faecal nitrogen
      due to an increased excretion of microbial nitrogen. A matter of controversy is
      the influence of dietary fibre on endogenous nitrogen excretion and factors
      affecting the losses of nitrogen in this way. It is not known if fibre acts as a
      secretogogue.

PMID- 8526736
TI  - The nutritional significance of endogenous N-losses along the gastro-intestinal
      tract of farm animals.
AB  - In animal production, endogenous protein losses associated with the digestion
      process are important losses, but difficult to measure. Measuring methods include
      feeding N-free diets, regression techniques based on amino acid profiles, and
      separating feed protein and endogenous protein by markers like homoarginine,
      hydrolysed casein or stable isotopes like 15N. Endogenous losses arise from
      saliva, digestive enzymes, bile, shedded epithelial cells and mucins and may be
      extra stimulated by the presence in feeds of antinutritional factors (ANF) such
      as lectins, trypsin inhibitors (TI), tannins and fibre. The impact of such
      factors may differ between non-ruminants and ruminants. The magnitude of the
      effect of the different factors is quantified and some of the consequences for
      protein deposition and nitrogen losses to the environment are discussed.

PMID- 8526737
TI  - [Effects of L-carnitine in poultry].
AB  - Because of the well established function of carnitine possible effects of
      carnitine were studied in poultry. In trial I it was investigated if carnitine
      and its precursors (lysine, methionine) reduce the formation of abdominal fat in
      broilers. Chickens (10 groups of 10 chickens each) were fed different diets
      (control, lysine and methionine in excess and deficient, respectively, with or
      without 5% fat supplement, L-carnitine and DL-carnitine supplement,
      respectively). Performance (body weight gain, feed conversion), amount of
      abdominal fat and carnitine concentration in blood, muscles (M. sartorius, M.
      pectoralis superficialis, cardiac), liver and kidney were determined. Performance
      and abdominal fat were influenced by dietary fat, lysine and methionine as
      expected and were not altered by carnitine. Excess and deficiency of lysine and
      methionine did not influence, fat supplement reduced and carnitine
      supplementation significantly increased tissue concentration of carnitine. In
      trial II it was studied if supplementation of a commercial layers' ration with
      either 500 mg L-carnitine or 500 mg nicotinic acid or both per kg reduces the
      cholesterol concentration in yolk. Influence on body weight, feed intake, laying
      performance, serum and yolk cholesterol concentration could not be observed, but
      yolk concentration of carnitine was significantly increased in supplemented
      groups. Trial III should clarify if the L-carnitine content in broiler parent
      stock ration influences hatchability. Four groups of 1350 hens each were fed a
      commercial all-mash supplemented with 0, 20, 50 and 100 mg L-carnitine,
      respectively. Hatching rate was increased from 83% to 87% and from 82.4% to 85.3%
      in groups supplemented with 50 and 100 mg L-carnitine, respectively, and in
      randomly sampled eggs of these groups carnitine concentration in yolk was higher.

PMID- 8526739
TI  - Subchronic toxicity of 3-phenylamino alanine, an impurity in L-tryptophan
      reported to be associated with eosinophilia-myalgia syndrome.
AB  - Consumption of certain product lots of L-tryptophan (LT) has been reported to be
      epidemiologically associated with an outbreak of eosinophilia-myalgia syndrome
      (EMS) in the United States. Since the production lots were found to contain 3
      phenylamino alanine (PAA) as an impurity, its effects were studied by
      administering the substance orally by gavage to 5-week-old Sprague-Dawley rats.
      Groups of animals were given PAA for 13 consecutive weeks at dose levels of 1, 10
      and 100 mg/kg per day. The animals were killed at 4 or 8 weeks. Hematological and
      blood biochemical tests were performed and detailed histopathological
      observations were made. No significant abnormalities were observed in the test
      animals and in particular no EMS-like conditions. A brief summary of other animal
      studies using several species of rats and mice performed in our laboratory since
      1989 on various LT related substances is also presented. No EMS-like effects were
      observed in these studies.

PMID- 8526738
TI  - Auditory and vestibular functions after single or combined exposure to toluene: a
      review.
AB  - Toluene is a widely used organic solvent, heavily employed in many manufacturing
      industries. Recently, evidence has begun to accumulate on the deleterious effect
      of toluene exposure has on the auditory and vestibular systems. Although little
      published information exists regarding these effects, the reported findings
      indicate a need for further investigation. The results of such investigations may
      dramatically affect occupational hearing conservation practices and legislation.
      Both human and animal studies will be summarized in discussing the effects of
      toluene alone or in combination with noise or other chemicals. Gaps in scientific
      knowledge are highlighted to assist future research.

PMID- 8526740
TI  - Phagocytes render chemicals immunogenic: oxidation of gold(I) to the T cell
      sensitizing gold(III) metabolite generated by mononuclear phagocytes.
AB  - The oxidizing capacity of phagocytic cells is suspected to play a major role in
      the generation of immunogenic drug metabolites, in particular those that cause
      extrahepatic immunopathological lesions. In the case of the antirheumatic drug
      gold(I) disodium thiomalate (Na2Au(I)TM), oxidation of the Au(I) ion to Au(III)
      appears to be responsible for the adverse immune reactions which may develop
      during gold therapy. Here, we show that the reactive metabolite Au(III) may be
      generated by mononuclear phagocytes (M phi) exposed to Au(I). The generation of
      Au(III) was analyzed by means of the adoptive transfer popliteal lymph node assay
      (PLNA) in mice, using T lymphocytes previously sensitized to Au(III) as a
      detection probe. Donors of the Au(III)-primed T cells were either directly
      sensitized to Au(III) by injection of tetrachloroauric acid (HAu(III)Cl4), or
      indirectly via chronic treatment with Na2Au(I)TM. As donors of peritoneal cells
      (PC), we used mice which had received weekly i.m. injections of Na2Au(I)TM for 12
      weeks and contained increased numbers of activated B cells. The PC of these mice
      were found to elicit a significant secondary response when used as antigenic
      material for the restimulation of Au(III)-primed T cells. The immunogenicity of
      PC obtained from Na2Au(I)TM-treated mice paralleled the total gold content of
      these cells. Noteworthily, M phi exposed to Au(I) in vitro also proved capable of
      eliciting a specific secondary response of Au(III)-primed T cells. Hence, M phi
      exposed to Au(I) generate the reactive intermediate Au(III) which, apparently via
      oxidation of self proteins, sensitizes T cells. As M phi are constituents of many
      different organs and, moreover, communicate with T cells, their capacity to
      generate Au(III) may account for the various extrahepatic adverse immune
      reactions induced by Au(I) drugs.

PMID- 8526741
TI  - Effects of paraquat, dinoseb and 2,4-D on intracellular calcium and on
      vasopressin-induced calcium mobilization in isolated hepatocytes.
AB  - The effects of the herbicides paraquat, dinoseb and 2,4-D on intracellular Ca2+
      levels and on vasopressin-induced Ca2+ mobilization were investigated in intact
      isolated hepatocytes. Incubation of rat hepatocytes with paraquat (5 mM for 60
      min) and dinoseb (10 microM) resulted in a time-dependent loss of viability by
      approximately 25%. Viability of cells treated with 2,4-D decreased significantly,
      dropping to about 20% at 10 mM and 60 min incubation. Exposure of hepatocytes to
      paraquat (1-10 mM) for 60 min had no effect on the basal level of [Ca2+]i.
      Additionally, exposure to paraquat had no effect on the magnitude and on the
      duration of the [Ca2+]i response to vasopressin. In the presence of 2,4-D (1-10
      mM), basal [Ca2+]i increases as a function of herbicide concentration. The
      magnitude of the delta[Ca2+]i response decreases from 256 +/- 8 nM in control to
      220 +/- 5 nM, at 10 mM 2,4-D. Exposure of hepatocytes to dinoseb (1-10 microM)
      had no effect on the basal level of [Ca2+]i. However, a strong concentration
      dependent decrease in the magnitude of delta[Ca2+]i in response to vasopressin
      was noticed at 60 min incubation. Dinoseb markedly inhibited the stimulation of
      the production of inositol phosphates by vasopressin stimulus. The present study
      demonstrates that paraquat, 2,4-D and dinoseb cause cell death in hepatocytes by
      mechanisms not related to an early increase in [Ca2+]i. Additionally, it has been
      shown for the first time that dinoseb disturbs the transduction mechanism
      promoted by vasopressin by inhibiting the formation of IP3.

PMID- 8526742
TI  - Assessment of the developmental toxicity of deferoxamine in mice.
AB  - Deferoxamine (DFO), an efficient chelating agent available for the treatment of
      iron and aluminium overload, was evaluated for developmental toxicity in Swiss
      mice. Intraperitoneal injections of DFO were given to pregnant animals at 0, 44,
      88, 176, and 352 mg/kg per day on gestational days 6 through 15. Maternal
      clinical status was monitored daily during and after treatment. Fetal parameters,
      including external, visceral, and skeletal malformations and variations, were
      assessed. Mice were killed on day 18. No maternal mortality was observed, but
      dams exhibited reduced body weight gain during treatment at 88, 176, and 352
      mg/kg per day. Body weight at termination, corrected body weight, and food
      consumption were reduced in all groups. In contrast, the only significant
      treatment-related embryo/fetal effect was a decrease in the number of live
      fetuses per litter at 352 mg/kg per day. The no-observable-adverse-effect level
      (NOAEL) for maternal toxicity of DFO was < 44 mg/kg per day, whereas the NOAEL
      for developmental toxicity was 176 mg/kg per day. In summary, intraperitoneal
      administration of DFO to mice during organogenesis produced developmental
      toxicity in the presence of maternal toxicity. Because of the remarkable maternal
      toxicity of DFO, extreme caution in the use of this drug is recommended during
      pregnancy.

PMID- 8526743
TI  - Development of a suspension organ culture of the fetal rat palate.
AB  - On the basis of an already established suspension organ culture system of mouse
      palate anlagen, we developed a corresponding culture system for rat palate
      anlagen. In order to optimize the culture results we systematically studied the
      influence of main "culture conditions" such as dissection technique, rotation
      speed, gassing schedule, and developmental stage at the onset of culture for mice
      and rat palate anlagen. This system allows culturing rat palate anlagen from day
      15 of gestation to day 18 + 8 h (80 h) under serum- and antibiotic-free
      conditions using a chemically defined medium, resulting in 90% fused palates. The
      explants, containing the maxillary vault and the palatal shelves, were cultured
      in siliconized culture flasks at a rotation speed of 12 rpm and a temperature of
      37 degrees C (Table 1).

PMID- 8526744
TI  - Nephrotic syndrome associated with N-hydroxyureas, inhibitors of 5-lipoxygenase.
AB  - The N-hydroxyurea derivatives 70C ((E)-N-[3-[3- (4-fluorophenoxy)phenyl[-1-(R,S)
      methylprop-2-enyl]-N-hydroxyurea) and its (R) 225C and (S) 404C enantiomers,
      which were being developed as 5-lipoxygenase inhibitors for the treatment of
      certain allergic and inflammatory conditions, were found to cause severe
      glomerulonephropathy in the rat. The lesion appeared to be of greater severity in
      female rats compared with male rats. In addition, 70C and 225C treated animals
      appeared more severely affected than 404C treated animals. Detailed examination
      of the lesion in animals dosed with 225C showed that there was a clear
      relationship between the onset of the lesion and the dose given, i.e. the higher
      the dose the sooner the lesion developed. The earliest changes detected in the
      kidney by transmission electron microscopy were noted in the glomeruli, in which
      the visceral cells appeared enlarged and showed varying degrees of foot process
      loss. In the more advanced lesion, the degree of foot process loss became more
      obvious and changes in the kidney tubules were seen by light microscopy. The
      morphological changes were mirrored by a dose-related increase in water
      consumption, an increased kidney to body weight ratio and gastrointestinal
      oedema, suggesting impaired renal function. Shortly after the onset of foot
      process loss, decreases in the total plasma protein and albumin and increases in
      the plasma cholesterol, triglycerides, urea and creatinine were recorded. These
      changes, particularly the foot-process loss, together with increased proteinuria,
      hypoalbuminaemia, hypercholesterolaemia and lipaemia, are all characteristic of
      "minimal change nephrotic syndrome". Because of the serious nature of the kidney
      lesion caused by these N-hydroxyureas in the rat, it was considered that it
      precluded their development as therapeutic agents for use in man.

PMID- 8526745
TI  - Altered hepatic eicosanoid concentrations in rats treated with the peroxisome
      proliferators ciprofibrate and perfluorodecanoic acid.
AB  - Several hypolipidemic drugs, plasticizers, and other chemicals induce hepatic
      peroxisome proliferation and hepatocellular carcinomas in rodents. These agents
      induce and promote hepatocarcinogenesis by unknown mechanisms, since most studies
      have not found them to be genotoxic. Peroxisome proliferators increase the
      expression of several genes, including those for the enzymes of the peroxisomal
      beta-oxidation pathway and the cytochrome P-450 4A family, which metabolize
      lipids, including eicosanoids and their precursor fatty acids. The peroxisome
      proliferators ciprofibrate and perfluorodecanoic acid (PFDA) were therefore
      examined for their ability to alter hepatic eicosanoid concentrations. Rats
      received injections of 3 or 10 mg PFDA/kg body weight every 14 days or were fed
      0.01% ciprofibrate for 10 days, 24 days, 6 weeks, 26 weeks, or 54 weeks. The
      activity of the peroxisomal enzyme fatty acyl CoA oxidase was significantly
      increased by both ciprofibrate and PFDA at all times. Hepatic concentrations of
      prostaglandins E2 and F2a (PGE2, PGF2a), thromboxane B2 (TXB2), and leukotriene
      C4 (LTC4) were measured by immunoassay. Concentrations of PGE2, PGF2a, and TXB2
      were decreased in livers of rats receiving ciprofibrate or PFDA compared to
      livers of control rats, with ciprofibrate exerting a greater effect than PFDA at
      the doses used. Hepatic LTC4 concentrations were significantly increased by
      ciprofibrate at 10 days and PFDA at 54 weeks, and significantly decreased by PFDA
      at 26 weeks. These alterations in eicosanoid concentrations may be important in
      the natural history of peroxisome proliferator-induced hepatocarcinogenesis.

PMID- 8526747
TI  - Glutathione-S-transferase (GST) theta polymorphism influences background SCE
      rate.
AB  - Polymorphism of glutathione S-transferase theta (GSTT1) modulates the toxicity of
      halogenated alkanes and epoxides in humans. The enzymatic activity of glutathione
      S-transferase theta and its corresponding gene is lacking in about 30% of the
      central European population. It has now been demonstrated that the background
      rate for sister chromatid exchange (SCE) is affected by this particular
      polymorphism. Smoking as a known inducer of SCE was taken into account. A group
      of GSTT1-positive subjects exhibited lower SCE rates than GSTT1-negative
      individuals (7.55 +/- 0.77 versus 8.74 +/- 1.24 SCE/mitosis, respectively, p <
      0.005). Non-smoking GSTT1-positive individuals showed the lowest SCE rate (7.26
      +/- 0.71 SCE/mitosis), significantly lower than the rates of smoking GSTT1
      positive and non-smoking GSTT1-negative subjects (8.14 +/- 0.55 SCE/mitosis and
      8.12 +/- 0.88 SCE/mitosis, respectively, p < 0.025 in both cases). Smoking GSTT1
      negative subjects exhibited the highest SCE rates (9.28 +/- 1.3 SCE/mitosis). It
      is hypothesized that GSTT1 is protective against background genotoxic damage.
      Since ethylene oxide is a proven substrate of GSTT1, the detoxification of this
      epoxide arising from endogenous ethylene may modulate SCE background rates.

PMID- 8526746
TI  - Modulation of cellular antioxidant defense activities by sodium arsenite in human
      fibroblasts.
AB  - Many studies have shown that oxygen radicals can be produced during arsenic
      metabolism. We report here that in human fibroblasts (HFW cells) sodium arsenite
      exposure caused increased formation of fluorescent dichlorofluorescein (DCF) by
      oxidation of the nonfluorescent form. The enhanced DCF fluorescence was inhibited
      by a radical scavenger, butylated hydroxytoluene. The effects of sodium arsenite
      treatment on cellular antioxidant activities were then examined. Treatment of HFW
      cells with sodium arsenite resulted in a significant increase in heme oxygenase
      activity and ferritin level. Sodium arsenite-enhanced heme oxygenase synthesis
      was inhibited by co-treatment of cells with the antioxidants sodium azide and
      dimethyl sulfoxide. Furthermore, sodium arsenite treatment did not apparently
      affect glucose-6-phosphate dehydrogenase activity, but resulted in significantly
      increased glutathione levels and superoxide dismutase activity, slightly
      decreased glutathione peroxidase activity, and significantly decreased catalase
      activity. Sodium arsenite toxicity was partly reduced by addition of catalase to
      the culture medium. These results imply that arsenite can enhance oxidative
      stress in HFW cells.

PMID- 8526748
TI  - [Basic pathogenetic mechanisms of chronic placental insufficiency].
AB  - Six basic mechanisms facilitating development of chronic placental deficiency,
      hypotrophy and fetal death are distinguished: 1) insufficiency of invasion of the
      extra-villous cytotrophoblast into the placental bed resulting in incomplete
      gestational restructuring of spiral arteries and reduction of uteroplacental
      circulation; 2) rheological disturbances in the intervillous space due to
      ultrastructural pathology of the glycocalyx and microvilli of the
      cytiotrophoblast; 3) pathological immaturity of microvilli and retraction of the
      diffusion surface; 4) disturbances of the villi perfusion resulting from
      prevailing development of the connective tissue components, reduction of stroma
      capillary bed and obliteration angiopathy at the level of supporting villi and
      umbilical cord; 5) placental barrier pathology; 6) endocrine deficiency resulting
      from the deficiency in the synthesis of human chronic gonadotropin during the
      first and, in part, second trimesters and the shortage of placental lactogen at
      the end of pregnancy.

PMID- 8526749
TI  - [Endocrine-cell stomach tumors].
AB  - Screening of the endocrine cell participation in the stomach carcinoma has been
      performed. Endocrine cells are found in all stomach tumors and those in which
      these cells occupy more than 75% of the surface are distinguished as endocrine
      cell carcinomas (ECC). They are subdivided into well (WD), moderately (MD) and
      poorly differentiated (PD). ECC are more frequently observed in males, their
      predominant location is cardia and fundus. The growth in the deep parts of mucosa
      and submucosa (this determines late clinical symptoms) is characteristic for
      these tumors. Alveolar, trabecular and glandular structural variants are observed
      in WD ECC and MD ECC, while PD ECC corresponded to small cell carcinoma (iat cell
      and intermediate types). Prognosis is unfavorable in MD ECC and PD ECC. Apart
      from this amacrine and combined tumors with an endocrine component are described.
      The authors emphasize the necessity to single out ECC from whole group of stomach
      carcinoma.

PMID- 8526750
TI  - [Carcinoid lung tumors: clinico-morphologic characteristics, diagnosis].
AB  - Review of the literature on carcinoid lung tumors covers classification, macro-
      and microscopical structure, prognosis of typical and atypical carcinoids, role
      of special staining methods and electron microscopy in their diagnosis. The role
      of electron microscopy in the diagnosis of a rare structural variant, oncocytic
      carcinoid, is emphasized.

PMID- 8526751
TI  - [Anti-macrophage monoclonal antibody D-11 in the diagnosis of histiocytic
      tumors].
AB  - Anti-macrophage monoclonal antibody (Mab) D-11 was tested in surgical material
      and biopsies of non-epithelial tumors and tumor-like lesions from 181 patients in
      order to assess possibility of using this Mab for diagnosis of histiocytic
      tumors, malignant fibrous histiocytoma in particular. The study was performed in
      parallel on cryostat sections and smears by immuno-peroxidase method. It is
      established that D-11 reacts positively with both histiocytic tumors and tumors
      of other genesis this being a limiting factor in differential diagnosis of
      histiocytic tumors. However, taking into consideration 100% of positive results
      with histiocytic tumors only, this antibody can be used for exclusion of tumors
      studied from the group of histiocytomas in cases of negative reaction.

PMID- 8526752
TI  - [Competence of diagnosis: chronic generalized infection, caused by hepatitis
      virus (B, C)].

PMID- 8526753
TI  - [Expression of glial fibrillary acidic protein and protein S-100 in cerebral
      astrocytic gliomas of varying degrees of malignancy (immunohistochemical study)].
AB  - Expression of the glial fibrillary acidic protein (GFAP) and S-100 protein was
      examined in 76 astrocytic gliomas (AG) with different degree of malignancy, which
      were subdivided into 4 groups: pilocytic astrocytoma, mixed astrocytoma,
      anaplastic astrocytoma and glioblastoma. Combined light-microscopical and
      immunohistochemical investigation detected several variants among different kinds
      of malignant AG that were distinguished by cytological composition and
      immunomorphology. Gemistocytic and polymorphic nuclear types were distinguished
      among anaplastic astrocytoma. Glioblastomas were subdivided into multiforme,
      isomorphic and gemistocytic variants. It was established that fractions of GFAP
      negative cells occur in benign and malignant AG. Thus, the presence of population
      of immunonegative cells in AG is not a sign of high-grade tumor anaplasia. Groups
      of GFAP-positive cells around tumor vessels were found in malignant AG only.

PMID- 8526754
TI  - [Various immunohistochemical markers of precancer and variants of prostate
      cancer].
AB  - The prostates of 45 patients with benign hyperplasia, precancer and carcinoma of
      the prostate were studied using histochemical and immunohistochemical methods.
      The correlation between the expression of the prostatic specific antigen and
      prostatic acid phosphatase according to the histological type of tumor and the
      level of differentiation of the prostatic intraepithelial neoplasia (PIN) was
      established. PIN is connected with acinar glandular epithelium. It occupies an
      intermediate position between well differentiated non-invasive carcinoma and
      large-acinar carcinoma. Cytospecificity of these antigens may be used as markers
      of premalignant lesions for differential diagnosis of precancerous processes in
      the prostate. Immunohistochemical properties of PIN may be used for revealing
      groups of a high risk.

PMID- 8526755
TI  - [Expression of gene K51 in normal epidermis and various epithelial skin tumors in
      man].
AB  - The expression of gene K51 in the cells of human normal epidermis and epithelial
      skin tumors was investigated using in situ hybridization method with radioactive
      probe. The K51 gene transcripts were detected in the epidermis, sebaceous and
      sweat glands of human embryo and adult skin. The level of gene expression was
      higher in the stratum granulosum than in the basal layer of the skin. K51 gene
      expression was also found in the basal cell and metatypical carcinomas, with the
      level of expression lower than in the neighbouring epidermis and higher than in
      the surrounding skin stromal cells. Thus, K51 gene is expressed in the skin
      epidermis of human embryo and adults but the level of its activity is
      dramatically decreased in the cells of skin epithelial tumors. This potentially
      may be important as a diagnostic test.

PMID- 8526756
TI  - [Morphologic heterogeneity of adrenal cortical adenoma].
AB  - 45 adrenal cortex adenomas were examined for morphological atypia after
      adrenalectomy. The majority of clear-, dark- and mixed cell adenomas are
      characterized by tissue atypia in the form of alveolar-trabecular structure.
      Adenoma heterogeneity is manifested by cellular polymorphism of a poor, moderate
      and high degree. It is suggested to distinguish adenomas formed of large, giant
      and multinuclear cells from dark cell adenomas and to consider them as a special
      independent giant cell variant.

PMID- 8526757
TI  - [Fibrosing alveolitis--current aspects of the problem].
AB  - Review of the literature and author's data on the etiology, pathogenesis and
      morphogenesis of fibrosing alveolitis (FA) which is a stereotype manifestation of
      the majority of lung interstitial diseases is presented. FA is characterized by
      an acute or chronic, focal or diffuse non-purulent inflammation of the
      interstitium of respiratory lung areas resulting in interstitial fibrosis. FA
      early stage is characterized by an exudative-productive inflammation, the late
      stage -by sclerotic changes resulting in a block of the aero-hematic barrier and
      development of the respiratory failure and hypoxia. A leading role in FA
      morphogenesis belongs to the cell cooperation including alveolar macrophages, T
      lymphocytes, fibroblasts and not infrequently polynuclear leukocytes. Alveolar
      macrophage is able not only to participate in the cell defence of lung tissue but
      to exert damaging sclerogenic effect as well. Nosological features of different
      interstitial lung diseases are better presented at an early stage of FA and are
      levelled in lung fibrosis progression.

PMID- 8526758
TI  - [Morphologic analysis of arrhythmogenic and non-arrhythmogenic zones of
      subendocardial areas of the heart in patients with rhythm disorders].
AB  - The signs of cardiomyocyte (CMC) apoptotic degeneration which is not specific for
      well differentiated heart tissue were found in both arrhythmogenic and non
      arrhythmogenic subendocardial zones. Contracted and over contracted CMC with
      characteristic ultrastructure and damaged inserted discs as well as atrophic CMC
      and cells with apoptotic degeneration were observed in the arrhythmogenic heart
      zones. These changes amy play a role in the genesis of rhythm disturbances.

PMID- 8526759
TI  - [Adaptive processes in heart failure (correlation and recombination)].
AB  - Comparative analysis of the relations between heart organometric parameters
      (linear, planimetrical, volume and weight) was performed in patients with chronic
      and acute heart failure and without failure as well as in healthy victims of
      violence. The minimal number of correlative links was found in patients without
      heart failure and the greatest number in patients with chronic heart failure,
      stage II and after a violent death. The results are interpreted in the light of
      D.S. Sarkisov's recombination theory.

PMID- 8526760
TI  - [Morphology of adaptive-compensatory processes in the myocardium as affected by
      contrasting temperatures].
AB  - A comparative morphologic study of Wistar rat myocardium under contrast
      temperature influences (extreme and moderate general cooling and general
      overheating) was carried out. It is shown that different regimens of general
      cooling and general overheating cause dramatic structural changes in the
      myocardium both at the tissue and subcellular levels. Tissue changes manifested
      as hemodynamic disorders, contracture and lytic injuries to cardiomyocytes
      resultant in necrobiosis and atrophy of some cardiomyocytes. These changes were
      more pronounced under acute influences. Tissue spatial myocardium reorganization
      had a stereotype pattern. Quantitative changes of main parenchymatous and stromal
      structure did not differ significantly under various temperature regimens. At
      subcellular level more pronounced quantitative and qualitative changes of
      organelles were revealed under general cooling irrespectively of the duration of
      the experimental exposure.

PMID- 8526761
TI  - [Subpopulations of lymphocytes and monocytes/macrophages at the early stages of
      human aorta atherosclerosis].
AB  - Human aorta was studied at early stages of atherosclerosis: intimal edema, first
      signs of lipoidosis, lipid spots and lipid plaques. Adhesion of Mn/Mp and
      lymphocytes to the aortal intima directly correlated with lipid deposits in the
      vascular wall. The number of mononuclear cells in the intima increased in
      parallel to progression of lipidosis. T-lymphocyte adhesion passed ahead of that
      of Mn/Mp. Cytotoxic suppressors dominated among T-lymphocytes adhered to the
      intima surface. Mn/Mp do not contain enzymes participating in the lipid
      utilization (acid lipase, acid phosphatase, nonspecific esterase) at initial
      stages of atherosclerosis. The activity of these enzymes starts to appear in
      parallel to atherosclerosis progression. HLA-DR antigen is found on the surface
      of T-lymphocytes and Mn/Mp indicating increased immunity of these cells.

PMID- 8526762
TI  - [Evolution of aortic atherosclerosis in specific European cities in the the 60's
      and 80's].
AB  - Repeated study of atherosclerosis epidemiology is performed in 5 European cities
      (Malme, Prague, Riga, Tallinn, Yalta) according to WHO recommendations 20 years
      after a similar study in the same regions. More frequent and more pronounced
      development of atherosclerosis in males of 20-39 years of age is found in the
      present study in 3 big cities (Prague, Riga, Tallinn) as compared to the
      population of small cities Malme and Yalta. The rejuvenation of atherosclerosis
      can not be explained by an ecological situation as in females atherosclerosis was
      most pronounced in Malme. Possible reasons of the evolution of atherosclerosis is
      discussed.

PMID- 8526763
TI  - [Morphologic features of immune interrelationships in the feto-placental system
      in development of a large fetus and in retardation of intrauterine fetal
      development].
AB  - Indirect criteria of the value of the immune placenta barrier in case of a large
      foetus are distinguished: relatively small volume of the fibrinoid substance,
      moderate synthesis by the syncytial epithelium of glucosaminoproteoglycans
      (GAPG), slight lymphoplasma cell infiltrates with a marked suppressor influence,
      the lack of antigens HLA = Dr on the trophoblast and formation of the adequate
      interrelation ship between the immune dependent placental structure and the
      thymus of the large foetus this allowing to retain the foetus up to 38-40 weeks
      or even more. In case of delay in the intrauterine foetus development there is a
      sharp increase of the fibrinoid substance, focal enhancement of GAPG production
      by the syncytial cells, decrease of the suppressor activity and the appearance in
      some cases in the trophoblast of antigens to HLA=Dr this being probably the
      manifestation of a premature exhaustion of compensatory-adaptive reactions in the
      placenta.

PMID- 8526764
TI  - [Morphologic diagnosis of a seronegative case of HIV-infection].
AB  - Morphological diagnosis is described of a seronegative case of HIV-infection
      resulting in AIDS-dementia and development of a generalized herpes and
      aspergillosis. The presence of HIV-antigens in the central nervous system and the
      spleen histologic sections confirmed morphological diagnosis.

PMID- 8526765
TI  - [Nature of pseudo-amyloid masses in lymphocytic pneumonitis].
AB  - The material of open lung biopsies from a female patient with lymphocytic
      pneumonitis affecting mainly lower parts of the lungs was studied light- and
      electron-microscopically, immunohistochemically. Diffuse lymphoplasmacytic
      infiltration with an admixture of macrophages, single giant multinuclear cells
      and pseudo-amyloid inclusions were found. Morphogenesis of pseudo-amyloid
      inclusions is related to processes of pulmonary fibro-atelectasis with subsequent
      imbibition by immunoglobulins (hyperglobulinemia was found in circulating blood).

PMID- 8526766
TI  - [This problem can be solved only by joint effort].

PMID- 8526767
TI  - [Biological markers of precancer of the large intestine].
AB  - Current views on focal defect in colorectal mucosa as a risk factor for
      development of tumours are presented. It is characterized by such phenotypical
      changes of the mucosa as cell proliferation activation, changes in ornithine
      decarboxylase activity and polyamine synthesis, changes in the expression of the
      blood group antigens and associated carbohydrate antigens as well as the
      development of small adenomas. All these changes may be biological markers of
      colonic precancer.

PMID- 8526768
TI  - [Embryogenesis of atrioventricular valve anomalies].
AB  - Formation of the atrioventricular valves under normal conditions is brought about
      after the completion of septation and envisages a sequential completion of
      atrioventricular fissure invagination, myocardium delamination and
      demuscularization of the folds. Anomalies of the atrioventricular valves are
      formed if the septation process or general principles of the valve formation are
      disturbed or if there is a combination of these factors. Specificity of the valve
      disturbances are determined by the causative factor.

PMID- 8526769
TI  - [++Chronic aortic insufficiency. Physiopathological and clinical peculiarities].

PMID- 8526770
TI  - [Research project, development, and funding request].

PMID- 8526771
TI  - [Transesophageal paracoronal transgastric imaging. Use and indications in
      pediatric cardiology].
AB  - PURPOSE: To evaluate the contribution and comparative value of paracoronal
      transgastric view compared with conventional transesophageal examination for
      morpho-functional assessment of different types of congenital heart disease in a
      pediatric group. METHODS: Fifteen patients with clinical and echocardiographic
      diagnosis of congenital heart disease were selected for single plane
      transesophageal examination. After routine evaluation, the probe was positioned
      to obtain a paracoronal transgastric view, and images that result from this
      technique were recorded and compared with those obtained in the conventional way.
      Eleven procedures were carried out in the cathlab and four in pediatric intensive
      care unit, under general anesthesia or heavy sedation. The age and weight were
      32.0 months and 11.6 kg respectively. No adverse reactions were observed with
      this method. RESULTS: In comparison with conventional transesophageal study, the
      paracoronal transgastric view permitted better morpho-functional assessment of
      the outlets of the right and left ventricles, as well as additional informations
      about the left pulmonary artery. CONCLUSION: Morphological and hemodynamic
      informations obtained from paracoronal transgastric view is a safe method which
      can be used either as an alternative or a complement to conventional examination
      to assess the outlets of both ventricles, as well as to evaluate the subvalvar,
      valvar and supravalvar region in different types of congenital heart disease.

PMID- 8526772
TI  - [Pulmonary valve agenesis. Clinico-surgical evaluation of 32 patients].
AB  - PURPOSE: To study the surgical and clinical evolution of 32 cases with absent
      pulmonary valve to propose the ideal period of time for surgical correction.
      METHODS: Clinical and laboratorial analysis were performed in 32 infants, under
      12 months of age, between 1980 an 1993, in an evolutive character. From the
      clinical viewpoint, hypoxic and/or congestive features were considered in
      previous and late periods related to surgical repair. Laboratorial studies as ECG
      (cavities overload), chest X-ray (cardiac size and pulmonary vascular markings)
      and echocardiogram (associated defects, pressure gradients and anatomical aspects
      of pulmonary arteries) were also analyzed. Cardiac catheterization was performed
      in 15 patients. RESULTS: Early cyanosis in 84% of cases and "to and for "murmur
      in 90% of them facilitate clinical diagnosis in whom tetralogy of Fallot was
      associated in 30 patients. Refractory respiratory and cardiac insufficiency were
      responsible for operative indication in 12 patients, half of them, operated on
      under 12 months of age, died. Survival patients were repaired between two to 11
      years old. Four deaths occurred early in life, before any surgical consideration
      and the 16 remaining patients will electively be considered for an opportune
      repair. CONCLUSION: Conservative clinical treatment is indicated, waiting for a
      more rigid bronchial wall can support the pressure of the dilated pulmonary
      arteries. This way, surgical repair is postponed for at least two years of age.

PMID- 8526773
TI  - [Hospital outcome of patients with right ventricular infarction and the
      importance of right coronary artery patency].
AB  - PURPOSE: To evaluate the importance of the right coronary artery (RCA) patency in
      patients with right ventricular infarction. METHODS: Fifty-two patients with
      inferior wall myocardial infarction and right ventricular involvement were
      studied and divided in two groups: group A (GA) included 35 patients in whom the
      RCA was patent at coronary angiography, and group B (GB), 17 who had an occluded
      RCA. They were prospectively evaluated for electrical and hemodynamic
      complications, as well as in-hospital mortality. RESULTS: The mortality in GA was
      11% and 29% in GB, p = 0.13; electrical complications were 11% in GA and 35% in
      GB, p = 0.06; hemodynamic complications were 8% in GA and 41% in GB, p = 0.009.
      CONCLUSION: These findings suggest a trend towards reduction in mortality and
      electrical complications, and significant reduction of hemodynamic complications
      in patients with inferior wall myocardial infarction with involvement of the
      right ventricle who have the RCA patent. Thus, RCA patency appears to be
      important in determining in-hospital outcomes of these patients.

PMID- 8526774
TI  - [Evaluation of post-intracoronary stent implant. Intravascular ultrasound versus
      quantitative angiography].
AB  - PURPOSE: To verify the minimal proximal and distal residual diameters by
      quantitative digital angiography and intravascular ultrasound, after the
      implantation of the intracoronary prosthesis. METHODS: We studied twenty patients
      with coronary atherosclerosis, ages ranging from 40 to 77 (56.7 +/- 10) years, 13
      (65%) were male. Patients with eccentric obstructive atherosclerotic lesions of
      70% or more in the proximal third of the anterior descendent, circumflex, or
      right coronary arteries received a stent implant as treatment for the
      obstruction. RESULTS: The mean proximal minimal residual diameters assessed by
      digital angiography were 3.32 +/- 0.33 mm and by ultrasound 3.08 +/- 0.31 mm (p <
      0.05); the distal diameters by angiography were 3.33 +/- 0.37 mm and by
      ultrasound 3.05 +/- 0.39 mm (p < 0.05). Therefore, the measurements by ultrasound
      were always smaller. There is a significant linear correlation between
      measurements by angiography and ultrasound for both proximal (r = 0.92; p <
      0.0001) and distal diameters (r = 0.91; p < 0.0001). The determination
      coefficient was 84% for proximal diameters and 87% for distal diameters.
      Therefore, the proximal diameters variate 16% and distal diameters 13% between
      both methods, due to the peculiarities of each method. CONCLUSION: Both methods
      correlate adequately, concerning to the measurements; the methods are
      interdependent, determining with the same accuracy intracoronary diameters in
      most cases studied; ultrasound is a safe and feasible technical resource for the
      evaluation of intravascular structures; the intravascular ultrasound system can
      contribute for the direct analysis inside the vascular structure, immediately
      after intracoronary stent implanting.

PMID- 8526775
TI  - [Mechanisms and dynamics of episodes of progression of of 2:1 atrioventricular to
      high degree atrioventricular block].
AB  - PURPOSE: To evaluate the mechanisms and dynamics of episodes of progression to
      high degree (HD) atrioventricular (AV) block (B) analyzed during incremental
      atrial pacing (St), in patients with previous 2:1 His-Purkinje (HP) AVB. METHODS:
      Data from 4 patients were analyzed. All of them with history of syncope and ECG
      exhibiting 2:1 AVB with wide QRS pattern. The AVB was in the HP system (HPS) in
      all. Every patient was submitted to electrophysiologic study with incremental
      atrial pacing, by which the conduction sequences and the AV conduction ratios
      (AVR) were analyzed. The basal (B) cycle length (CL) was defined as the shortest
      interval between two conducted beats (spontaneous or pacing-induced). The
      incremental atrial stimulation was performed beginning with CL 10 msec shorter
      than BCL until reaching 250 msec. RESULTS: Nineteen episodes of progression to HD
      AVB were seen. A) With StCL between 31 and 26% of BCL, AVR were 3:1, 4:1 and 5:1,
      with only one blocking zone (BZ) in the HPS; B) with StCL between 24 and 22% of
      BCL, AVR were 5:1, 7:2, 9:2e11:3. In this situation a 2nd BZ ensues-on proximal,
      site of a decremental conduction, situated in the AV node (AVN) or in the HPS,
      and the other (distal level) always in HPS; C) with StCL between 24 and 16% of
      BCL, AVR were 5:1, 6:1, 10:2, 11:2 and 12:3. Here, these AVR were explained by
      postulating 3 BZ where 2 were in AVN and 1 in HPS, or inversely with 1 in AVN and
      2 in HPS. The decremental conduction occurred in 1 or 2 out 3 BZ and an integral
      conduction (like 2:1 or 3:1) in the others. CONCLUSION: The BCL is the
      determinant of the AVR observed. As the StCL is shortened (< 26% BCL) a 2nd or
      3rd BZ in the AVN or in the HPS ensues. These observations suggest that the
      mechanisms and dynamics of progression to HD-AVB apply only during incremental
      atrial pacing and there is a clear difference with what has been observed with
      the progression occurring exclusively at AV node.

PMID- 8526776
TI  - [Clinico-morphological dissociation in patients with mitral valve stenosis].
AB  - PURPOSE: To study characteristics of the natural history of mitral stenosis (MS)
      in patients that have no correlation between mitral valve areas (MVA) and
      symptoms. METHODS: We studied 18 patients with MS, that presented no correlation
      between MVA and functional class (FC), 16 (89%) were female and two (11%) men,
      with age ranging from 16 to 54 (mean 33) years. Patients assigned to group A (8
      cases) had FC III and MVA > or = 1.5 cm2 and group B (10 cases) FC I/II and MVA <
      1.1 cm2. FC and MVA at the start (initial time-It) and after 12 months or before
      surgical correction (SC) or percutaneous mitral balloon valvuloplasty (PBV)
      (final time-Ft) were compared. All patients with predict O2 uptake (%PRED VO2) at
      It were evaluated. RESULTS: Five (63%) patients of group A, that maintained MVA >
      or = 1.5 cm2, changed to FC I/II but three (38%) needed a SC or PBV (2 with
      lesser MVA at Ft). At group B, six (60%) patients needed SC or PBV. CONCLUSION:
      MS patients with MVA > or = 1.5 and FC III, providing MVA do not decrease,
      improves their FC, becoming it more compatible with MVA %PRED VO2. The cases of
      group B presented the greatest probability of needing SC or PVB.

PMID- 8526777
TI  - [Psychological factors influencing smoking persistence in coronary patients].
AB  - PURPOSE: To study the psychological factors influence on the maintenance of
      smoking in coronary patients. METHODS: Questionnaire was applied in 40 smoking
      coronary patients, to investigate the tobacco's dependence type and degree,
      resistance degree, readiness level to abstinence and attitudes/emotions that
      favors tobacco's use. Male sex was predominant (75%) with age ranging from 25 to
      80 (mean 52) years. RESULTS: Regarding the tobacco psychological type dependence,
      75% of patients smoke to lower tension, 47.5% presenting a moderate resistance to
      quit smoking. Concerning the readiness to abstinence, 42.5% of patients were
      found to be in the contemplative stage. CONCLUSION: The coronary patient quit
      smoking treatment must include interventions aimed to provide instruments to cope
      with stressful situations and to increase the motivation to reach an action and
      maintenance abstinence smoking stage.

PMID- 8526778
TI  - [Preoperative erythrocytopheresis in a patient with SC hemoglobinopathy and
      mitral stenosis].
AB  - Hemoglobinopathies are associated with thrombotic complications, when exposed to
      cardiopulmonary bypass. A 54-year old, black woman with hemoglobinopathy SC and
      severe mitral stenosis was submitted to eritrocytopheresis 48 hours before mitral
      commissurotomy surgery. The therapeutic determined appearance of the percentual
      hemoglobin A of 68% with reduction the hemoglobin S of 48% to 15% and the
      hemoglobin C of 51% to 17%. No complications occurred during postoperative
      period. To best of our knowledge, that is the first report about application the
      eritrocytopheresis in the pre operative extra corporeal circulation care in
      surgical treatment of patients with chronic rheumatic heart disease and
      hemoglobinopathy SC.

PMID- 8526779
TI  - [Coronary angioplasty through the transradial approach].
AB  - We describe a coronary angioplasty procedure performed by transradial approach,
      on a 53 year old male with a reestenotic lesion in his right coronary artery,
      done 19 months after the initial dilatation. This is a new technique and has not
      been applied in our country.

PMID- 8526780
TI  - [Case 3/95. Instituto do Coracao do Hospital das Clinicas FMUSP].

PMID- 8526781
TI  - [Ischemic heart disease and occupational exposure to chemical substances. Review
      of the literature].

PMID- 8526782
TI  - [Multicenter National Study for the evaluation of the efficacy and tolerance of
      nifedipine oral release osmotic system in mild to moderate hypertension].
AB  - PURPOSE: Evaluation of the efficacy and tolerability of nifedipine oros in
      patients with mild to moderate essential hypertension without major target organ
      damage and the anti-hypertensive effect along the 24 hours. METHODS: Two hundred
      and three patients were studied. After two weeks placebo running period single
      dose of nifedipine oros (30 mg/day) was administered for 8 weeks. At the end of
      the 4th week, the non-responders (diastolic blood pressure > 90 mmHg or reduction
      in diastolic pressure < 10 mmHg), had the dosage increased to 60 mg/day.
      Laboratory tests and 24h blood pressure monitoring (60 patients) were performed
      at the beginning and at the end of the study. RESULTS: One hundred and ninety one
      patients completed the study. Fifty nine percent were considered responders at
      the end of the 4th week with nifedipine oros 30 mg/day and 41% needed dosage
      increment to 60 mg/day. At the end of the 8th week, all patients were considered
      responders to nifedipine oros. The blood pressure control extended throughout the
      24h of the day. The most common adverse events were edema (14.6%) and headache
      (12.4%). Good and very good tolerability were informed by 85% of the patients.
      CONCLUSION: Nifedipine oros was able to control blood pressure efficaciously
      along the 24h period without important side effects. The possibility of once day
      dosage, increases the patient adherence to anti-hypertensive therapy.

PMID- 8526783
TI  - [Guidelines of the Brazilian Cardiology Society on coronary transluminal
      angioplasty].

PMID- 8526784
TI  - [Transesophageal echocardiography. A new window to the heart].

PMID- 8526785
TI  - Necessity for long-term vision by government agencies in the world for the
      development of a TAH.

PMID- 8526786
TI  - Lactate versus bicarbonate on-line hemofiltration: a comparative study.
AB  - In this study, 6 chronic anuric uremic patients underwent lactate hemofiltration
      (HF) with a substitution fluid, prepared in bags, for 3 months and bicarbonate
      HF, with continuous on-line preparation of the substitution fluid, for 3 months.
      We determined Na+, Cl-, K+, total calcium (Ca), ionized calcium (Ca2+),
      phosphate, intact parathormone (I-PTH), pH, PCO2, PO2, and HCO3- in plasma
      before, during, and after the treatment, as well as Ca, Ca2+, phosphate, and I
      PTH in the ultrafiltrate. Moreover, heart rate (HR) and mean arterial pressure
      (MAP) were continually recorded during the procedure. Furthermore, the patients
      underwent echocardiographic study before and after the session. In comparison
      with lactate, bicarbonate HF caused a significant increase in HCO3- and a
      decrease in K+ plasma concentrations. This was detectable, with lower
      significance, even 44 h after the end of the treatment. At the end of the long
      interdialytic period (68 h after the end of the treatment), no significant
      difference was detectable. pH and PCO2 showed a significant but transient
      increase during HF. The other parameters investigated did not differ
      significantly between the two methods.

PMID- 8526787
TI  - Modulation of idiotypic and antiidiotypic immunoglobulin G responses in an immune
      thrombocytopenic purpura patient as a consequence of extracorporeal protein A
      immunoadsorption.
AB  - Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by
      the presence of antiplatelet antibody which sensitizes platelets resulting in
      their clearance by the reticuloendothelial system. Extracorporeal protein A
      immunoadsorption has been demonstrated to be of benefit in the treatment of this
      autoimmune disorder. In the present study, a patient with underlying systemic
      lupus erythematosus (SLE) presented with ITP. The patient received 14
      immunoadsorption treatments and responded to therapy. During the course of
      immunoadsorption treatments, there was a decline in circulating immune complex
      (CIC) levels, antinuclear antibody (ANA) levels, and antiplatelet IgG antibody
      levels. In addition, elevated levels of antiidiotypic IgG antibody detected
      before initiation of therapy were significantly reduced during the course of
      immunoadsorption treatments. This study suggests that specific autoimmune
      idiotypic IgG antibody and corresponding antiidiotypic IgG antibody responses may
      be modulated in association with extracorporeal immunoadsorption employing
      protein A/silica columns.

PMID- 8526788
TI  - Development of immunosorbents for apoB-containing lipoproteins apheresis.
AB  - Three types of sorbents were developed for the specific removal of atherogenic
      apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL (a) (Lp[a])
      from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse
      monoclonal antibodies against human apoprotein B-100. The third one was intended
      for specific removal of Lp(a) and contains sheep antibodies against human Lp(a).
      Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL
      immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted
      during 3 years. The results showed that extracorporeal immunosorption is safe and
      effective for lowering LDL and Lp(a). These procedures may be used both for
      metabolic investigations and for studies on possible regression of
      atherosclerosis.

PMID- 8526789
TI  - The role of plasma exchange in the treatment of severe forms of hemolytic-uremic
      syndrome in childhood.
AB  - Therapeutic plasma exchange (PE) or plasma-pheresis has been used in recent years
      in the treatment of severe hemolytic uremic syndrome (HUS) in children. We
      analyzed the benefit of PE and peritoneal dialysis (PD) in 9 children, 6 boys and
      3 girls, aged 1-10 years, from 1983-1993. All children came from different
      geographical regions, and all had the sporadic form of the illness. Three
      patients had the gastrointestinal form, 5 had respiratory prodromes while 1 child
      developed HUS during the course of varicella. Seven children were hypertensive,
      but only in 3 was hypertension persistent. The child with varicella had a
      transient complement decrease. Five children were treated with PE. In 4 children,
      fresh frozen plasma (FFP) was used as replacement fluid, and human albumin was
      used in 1 child. Four children were treated with PD and infusions of FFP. Rapid
      recovery of renal function was observed in 5 patients whereas in 2 oliguric
      children the recovery of renal function ensued within 1 and 2 months,
      respectively. Two children developed terminal renal failure (TRF) (in 1 child the
      treatment was very delayed, and in other child HUS developed following
      varicella). Only 1 boy had relapses of the disease followed by impairment of
      renal function from which he gradually recovered. During the 3-10 year follow-up
      period, only the child with relapses was hypertensive while the others had normal
      clinical and laboratory parameters. We suggest that PE plays an important role in
      the early treatment of severe forms of HUS in children.

PMID- 8526790
TI  - Intraarterial perfusion of the hindlimb with pyridoxalated hemoglobin
      polyoxyethylene conjugate solution in anesthetized dogs.
AB  - To evaluate the potential clinical usefulness of a modified hemoglobin,
      pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), the hindlimb vascular
      bed was perfused with PHP solution while monitoring tissue oxygen tension (PtO2)
      in anesthetized dogs. The hindlimb region was perfused through the external iliac
      artery with a roller pump at a varying perfusion rate. PtO2 was measured using a
      PO2-monitoring probe inserted into the gracial muscle. After surgical preparation
      for perfusion, the iliac arterial flow rate was 19.9 +/- 5.6 ml/min, and baseline
      PtO2 was 38.4 +/- 1.3 mm Hg. Perfusion with autologous arterial blood with the
      pump increased PtO2 and perfusion pressure (PP) in a perfusion rate-dependent
      manner. Perfusion with PHP solution at 20 ml/min decreased PtO2 from the initial
      baseline level, but an increase in the flow rate to 40-55 ml/min restored or
      induced an elevation of PtO2. Results demonstrated that PHP solution can deliver
      oxygen to local tissue and maintain tissue oxygen tension at the same level as
      autologous arterial blood at a high enough flow rate.

PMID- 8526791
TI  - Cannula selection and cannulation techniques for nonpulsatile mechanical
      ventricular assistance.
AB  - The successful use of mechanical ventricular assistance is, in large part,
      dependent upon easy insertion of well designed inflow and outflow cannulas. This
      manuscript describes a family of cannulas specifically designed for use in a
      nonpulsatile ventricular assist device (VAD) circuit. Although a variety of
      commercially available cannulas can be employed in a nonpulsatile VAD circuit,
      the cannulas described in this manuscript possess a number of unique design
      features. The reinforced thin-walled design and end hole construction optimize
      fluid flow characteristics in both the inflow and outflow cannula. The extended
      length allows the cannulas to transverse the skin at a point far distant from the
      mediastinum, reducing the potential for ascending cannula site infection. The
      purpose of this manuscript is not to review all cannulas available for
      nonpulsatile VAD circuits, but rather to describe in detail a family of cannulas
      that are ideal VAD cannulas based on their design characteristics. In addition
      individual cardiac surgeons implant very few of these devices annually. Thus the
      advantages and disadvantages of common cannulation sites and a proven technique
      for cannula insertion will also be presented.

PMID- 8526792
TI  - Influence of the compliance of the pump housing and cannulas of a paracorporeal
      pneumatic ventricular assist device on transient pressure characteristics.
AB  - The dependence of transient pressure characteristics of a ventricular assist
      device (VAD) on the compliance of its housing and cannulas was investigated in a
      mock circulation. The peak rate of change of pressure (dP/dtmax) values was
      greater in the cannulas than other compartments and was associated with valve
      closure-induced pressure oscillations. When cannula compliance was increased from
      0.0057 to 0.0129 cm3/mm Hg, these values decreased by approximately 20%, and
      outflow cannula pressure oscillation frequency decreased from 17.5 Hz by 35%.
      This trend was also apparent in the inflow. A VAD housing compliance increase
      from 0.0162 to 0.0483 cm3/mm Hg caused a dP/dtmax decrease of 30% in both the
      blood chamber and the outflow cannula. The effect of this change on the inflow
      was weaker implying that housing absorbs the energy associated with outflow
      deceleration more effectively than the inflow. These findings suggest that
      increasing VAD housing and cannulas compliance can improve hydrodynamic
      performance.

PMID- 8526793
TI  - Constructional and functional characteristics of recent total artificial heart
      models TNS Brno VII, VIII, and IX.
AB  - Twelve total artificial heart (TAH) models have been developed at the Brno
      Research Center. Devices VII, VIII, and IX were constructed on the principle of
      asymmetry. Three main objectives had to be fulfilled by this construction. First,
      contact of the flap inflow valve with the diaphragm during the pumping cycle had
      to be avoided. Second, the evacuation regimen of the blood chamber needed to be
      improved. Third, the danger of thrombi formation due to the lesser incidence of
      the dead corners had to be decreased or eliminated. The type VII heart has a roof
      shaped polyurethane valve in the outflow tract whereas the type VIII heart has a
      flap valve. The decrease of thrombi incidence around the outflow valve was thus
      secured, and the driving pressure was decreased as well. In the type IX heart,
      the small additional flap valve is attached to the outflow valve. In one Brno VII
      device, Imachi's jellyfish valve has been mounted. Altogether, 62 long-term
      experiments with survival times of 30-314 days have been performed. To this
      number, 4 comparative experiments using the Rostock artificial heart were added.

PMID- 8526794
TI  - Kinetics of phenols in body fluid compartments during hemodialysis.
AB  - On the basis of direct quantification of hemodialysis (HD), the kinetics of
      phenols (Ph) were followed in 13 patients on regular HD treatment. The average
      plasma levels of Ph before and after HD were 627 +/- 109 mumol/L and 416 +/- 81
      mumol/L, respectively. The total amount of Ph removed during 5-h HD was 7,481 +/-
      1,894 mumol. For calculation of the generation rate (G), a new formula has been
      derived not requiring knowledge of the corresponding volume of distribution. The
      G of Ph was 2.9 +/- 0.7 mumol/min on average. The mean dialysis clearance (K) of
      Ph was 48.2 +/- 10.2 ml/min.

PMID- 8526795
TI  - Mammalian erythrocytes as physiological carriers of fluorescent exogenous agents:
      a comparative study of bovine and camel red blood cells.
AB  - Recently attention has been focused on the investigation of new and effective
      routes for drug administration in order to avoid their side effects in the human
      body. Red blood cells (RBCs) exhibit many advantages, i.e., they are naturally
      occurring, biodegradable, and non-immunogenic. Their use as drug carriers has
      many potential applications, including slow drug delivery to the body tissue and
      drug targeting to a specific site. In this work, the fluorescent exogenous agent
      sodium fluorescein (uranin) was used as the probe for the encapsulation of the
      RBCs. The encapsulation process was applied in two different mammalian RBCs:
      camel and bovine. The results indicate that the encapsulation efficiency of
      bovine RBCs was 34.0 +/- 3.0% with an RBC recovery rate of approximately 75%
      whereas that of camel RBCs was only 8.0 +/- 2.0% with a cell recovery rate of
      approximately 47%. These differences demonstrate the dependency of the
      encapsulation process on the type of mammalian source of the RBCs.

PMID- 8526796
TI  - From womb to tomb: the Brno TAH story.

PMID- 8526797
TI  - Inhaled nitric oxide for the management of acute right ventricular failure in
      patients with a left ventricular assist system.

PMID- 8526798
TI  - Induction of odontoblast-like cell differentiation in dog dental pulps after in
      vivo implantation of dentine matrix components.
AB  - The effects of dentine extracellular matrix components on dental mesenchymal
      cells were studied by light and transmission electron microscopy after their
      implantation at central sites of mechanically exposed pulps in dog molar teeth.
      The implants were Millipore filters that had been soaked with solutions
      containing 30 or 300 micrograms/ml of an EDTA-soluble fraction of rabbit incisor
      dentine. Control filters were soaked with dog albumin or phosphate buffered
      saline. Columnar, polarized cells were consistently seen after 8 days in close
      proximity to the filters coated with both concentrations of dentine matrix
      components. Characteristic features of these polarized cells included widened
      cisternae of the rough endoplasmic reticulum, a rich microfilamentous network in
      the long cytoplasmic extensions invading the filter pores and numerous
      cytoplasmic bodies. These cells also showed evidence of functional as well as
      cytological differentiation. Polarized processing of secretory granules could be
      observed after 8 days' implantation, and also the presence of matrix vesicles and
      deposition of a fine, collagenous matrix into the filters apically to the distal
      end of the cytoplasmic processes. After 24 days' implantation, secretion of a
      tubular matrix could be consistently seen in association with the odontoblast
      like cells. No changes in cell organization or matrix synthesis were seen after
      implantation of control filters. These studies demonstrate that bioactive
      components present in the EDTA-soluble dentine matrix fraction are able to
      directly induce cell polarization and apical secretion of tubular matrix when
      implanted in contact with dental pulp cells at sites remote from the odontoblast
      layer.

PMID- 8526799
TI  - Three groups of afferent pulpal feline nerve fibres show different
      electrophysiological response properties.
AB  - Responses were recorded, after the application of four types of stimuli (slow or
      rapid elevation of temperature, hydrostatic negative pressure through thin
      dentine, and bradykinin directly applied to exposed pulp), from functional single
      fibres innervating the cat lower canine tooth pulp, dissected from the inferior
      alveolar nerve. A total of 278 single pulpal fibres were isolated. A fibres (n =
      220) were divided into two groups: one (FA; fast A fibre, n = 160) consisting of
      those whose conduction velocities (CVs) were more than 2 m/s both inside and
      outside the tooth pulp, and the other (SA delta; slow A delta fibre, n = 60)
      consisting of those whose intrapulpal CVs were less than 2 m/s and extrapulpal
      CVs greater than 2 m/s. Fifty eight C fibres (C) were also found. None of FA, 40%
      of SA delta and 52% of C responded to continuous heat. None of C, 47% of FA and
      45% of SA delta responded to rapid elevation of temperature. None of C, 20% of FA
      and 20% of SA delta responded to hydrostatic pressure. None of FA, 83% of SA
      delta and all of C responded to bradykinin. It was found that 21 of 60 SA delta
      responded to both types of stimuli that reportedly activate only A (rapid heat
      and hydrostatic negative pressure) or C (continuous slow heat and bradykinin)
      nerve fibres and that 29 SA delta responded to slow heating and/or bradykinin,
      similar to C fibres.

PMID- 8526800
TI  - Purification and characterization of Porphyromonas gingivalis outer membrane
      antigens.
AB  - Porphyromonas gingivalis is strongly associated with periodontal disease.
      Significant titres of specific IgG antibodies to P. gingivalis can be found in
      healthy individuals and those with periodontitis. In this study, 22 outer
      membrane antigens ranging from 15.5 to 107.6 kDa were recognized by sera from
      persons with periodontitis and controls. Serum from individuals with
      periodontitis showed a significantly higher IgG response to a 31.4-kDa antigen (p
      < 0.05); serum from those with gingivitis demonstrated a significantly higher
      response to a 15.5-kDa antigen (p < 0.05). The response to the 15.5-kDa antigen
      might represent a protective immune response while that to the 31.4-kDa could
      serve as a marker for disease susceptibility. These two antigens were purified to
      homogeneity and their N-terminal amino acid sequences determined. The sequences
      did not correspond to any previously described P. gingivalis antigens. The role
      of these two antigens in the pathogenesis of periodontal disease remains to be
      determined.

PMID- 8526801
TI  - Effects of chlorhexidine on human taste perception.
AB  - Chlorhexidine gluconate at a dose used to control bacteria in the mouth has a
      reversible effect on taste perception. Taste-intensity ratings and taste-quality
      identification for concentration series of sucrose, sodium chloride, citric acid
      and quinine hydrochloride were obtained from 15 healthy humans. The participants
      rinsed with 0.12% chlorhexidine for 3 min twice a day. Each individual was tested
      3 times: before the 4-day rinse period, 30 min after the final rinse, and 4 days
      after the rinse period. Chlorhexidine rinses reduced the perceptual intensity of
      sodium chloride and quinine hydrochloride, not sucrose or citric acid. No effects
      on taste perception were detected 4 days after the rinse period. The
      identification of sodium chloride as salty was seriously impaired by
      chlorhexidine but the identification of quinine hydrochloride as bitter was not
      affected. Specific sites of action of chlorhexidine on the taste epithelium are
      not known but its effects on salty taste may be related to its strong positive
      charge and its effect on bitter taste may be related to its amphiphilicity.
      Chlorhexidine has promise as a probe of taste transduction, as well as for the
      management of salty/bitter dysgeusias in humans.

PMID- 8526802
TI  - Protein tyrosine phosphorylation induced by epidermal growth factor and insulin
      like growth factor-I in a rat clonal dental pulp-cell line.
AB  - Both epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I)
      produce a dose-dependent stimulation in the rate of cell division in a rat clonal
      dental pulp-cell line (RDP 4-1). To elucidate the initial mitogen-induced
      cellular events that may mediate mitogenic action, the effects of EGF and IGF-I
      on cellular protein tyrosine phosphorylation were examined. In a dose-dependent
      manner, EGF (1-100 ng/ml) transiently stimulated tyrosine phosphorylation in four
      major proteins with apparent molecular weights of 220, 180, 140 and 120 kDa, and
      in five other more minor proteins (90, 80, 65, 55 and 44 kDa). IGF-I (1-100
      ng/ml) dose-dependently stimulated the tyrosine phosphorylation of 160- and 140
      kDa proteins, and had a smaller effect on the 80-, 65- and 44 kDa proteins. In
      contrast to the action of EGF, IGF-I-induced tyrosine phosphorylation was
      sustained for more than 60 min, particularly that of the 160-kDa phosphoprotein.
      From the results of specific immunoprecipitation/Western-blot analyses, the 180
      kDa EGF-sensitive protein could be identified as the EGF receptor (EGF-R). Among
      the IGF-I-sensitive pulp cell proteins, the 160-kDa protein was identified as
      insulin-receptor substrate-1. Both mitogenic treatments stimulated the tyrosine
      phosphorylation of a weak, 44-kDa protein, which we have identified as the
      extracellular signal-regulated kinase-1. Despite the presence of phosphoproteins
      of the correct size, neither the IGF-I receptor (IGF-I-R) nor the phospholipase C
      gamma-isoform could be identified as tyrosine kinase substrates in either
      treatment. Pretreatment with the tyrosine kinase inhibitor genistein (20
      micrograms/ml) significantly inhibited EGF- and IGF-I-induced tyrosine
      phosphorylation in permeabilized RDP 4-1 cells, and the tyrosine phosphatase
      inhibitor orthovanadate (1 mM) significantly prolonged the duration of the
      mitogen-stimulated tyrosine phosphorylation in both intact or permeabilized
      cells. Phorbol 12-myristate 13-acetate (100 nM), which activates protein kinase C
      (PKC), inhibited the tyrosine phosphorylation induced by either growth factor.
      This action was blocked by pretreatment with staurosporine (200 nM, 15 min), a
      selective PKC inhibitor. However, neither removing external Ca2+ with EGTA (1 mM)
      nor inducing Ca2+ influx with A23187 ionophore (2 microM) significantly altered
      EGF- or IGF-I-induced phosphorylation. These findings strongly suggest that
      authentic EGF-R and IGF-I-R on RDP 4-1 cells are coupled to complex, tyrosine
      kinase-mediated, intracellular signalling systems that are sensitive to a PKC
      dependent mechanism. EGF- and IGF-I-induced tyrosine phosphorylation cascades may
      have important roles in vivo in the regulation of dental pulp-cell proliferation
      and ultimately may affect dentine formation.

PMID- 8526803
TI  - An immunohistochemical and monastral blue-vascular labelling study on the
      involvement of capsaicin-sensitive sensory innervation of the junctional
      epithelium in neurogenic plasma extravasation in the rat gingiva.
AB  - Nerve fibres immunoreactive for substance P (SP) and calcitonin gene-related
      peptide (CGRP) were located preferentially at the base of the junctional
      epithelium. Occasional fibres were observed in close proximity to the
      subepithelial, small blood vessels. The vascular connective tissue papillae
      projecting into the epithelium were more densely surrounded by SP- and CGRP
      immunoreactive fibres in the interdental col than in other regions of the
      gingiva. In some cases, hyperplasia of the junctional epithelium was noted in the
      interdental col where the connective tissue papillae were invaded by widened
      vessels, indicating severe irritation. SP- and CGRP-immunoreactive fibres around
      these papillae showed increases in their immunoreactivity and thickness, with
      some fibres terminating as large expansions. Double immunohistochemical staining
      revealed the co-existence of SP and CGRP in all nerve fibres within and under the
      junctional epithelium. Capsaicin pretreatment eliminated most of the
      immunoreactivity for both peptides. Intravenous infusion of capsaicin or SP
      caused increased permeability in vessels underlying the junctional epithelium, as
      indicated by Monastral blue labelling. Labelled vessels were arranged not only in
      a network extending under the epithelium but also in loops protruding into the
      connective tissue papillae. These labelled vessels were most abundant in the
      interdental col, where vascular loops with more complex configurations exhibited
      strong staining in their walls. In the case of hyperplasia of the junctional
      epithelium in the interdental col, widened vessels showing extensive labelling in
      their walls were observed. In capsaicin-pretreated animals, capsaicin-induced
      extravasation was abolished, while the effect of SP was still observed. These
      findings provide evidence that capsaicin-sensitive sensory nerves supplying the
      junctional epithelium are involved in neurogenic plasma extravasation in the rat
      gingiva. The enhancement of neurogenic plasma extravasation in the col may be
      vascular response associated with a higher susceptibility of this region to
      gingival inflammation.

PMID- 8526804
TI  - Detection of interleukin-1 beta mRNA-expressing cells in human gingival
      crevicular fluid by in situ hybridization.
AB  - Interleukin-1 beta (IL-1 beta) mRNA-expressing cells in human gingival crevicular
      washings (GCW) obtained from patients with periodontitis and healthy controls
      were examined by in situ hybridization. GCW was done at 15 diseased sites
      [Gingival Index > 1; pocket depth > or = 5 mm] from five patients with adult
      periodontitis and eight clinically periodontal healthy sites from three
      volunteers GI < or = 1; PD < or = 3 mm), and then the samples were
      cytocentrifuged. In situ hybridization using digoxigenin-labelled oligonucleotide
      probe complementary to human IL-1 beta mRNA showed IL-1 transcripts in both
      polymorphonuclear leucocytes and mononuclear cells but not in epithelial cells in
      all GCW samples from diseased and healthy sites. Polymorphs were the predominant
      leucocytes in diseased and healthy sites, averaging 91.7 +/- 4.6 and 77.0 +/-
      10.3%, respectively. The percentages of IL-1 beta mRNA-positive polymorphonuclear
      leucocytes in GCW samples from diseased and healthy sites were 92.3 +/- 4.7 and
      80.9 +/- 10.3%, respectively. The IL-1 beta gene signals in individual cells were
      quantified in five samples (two healthy and three diseased sites). The mean
      amounts of IL-1 beta mRNA expression in polymorphonuclear leucocytes was higher
      than that of mononuclear cells in all samples and there was heterogeneity within
      the populations of polymorphonuclear and mononuclears cells in their ability to
      express the IL-1 beta gene. These findings indicate that IL-1 beta may be
      predominantly produced by polymorphonuclear leucocytes in the gingival crevice of
      patients with adult periodontitis and periodontally healthy controls.

PMID- 8526805
TI  - Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of human whole saliva.
AB  - The purpose of this study was to characterize the electrophoretic patterns of
      human resting and stimulated whole saliva. Pooled and individual, uncentrifuged,
      unprocessed whole saliva from 20 healthy, unmedicated individuals was run on
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis and stained with
      Coomassie blue R-250. Similar and characteristic patterns for whole saliva were
      observed for all samples, consisting of over 34 blue- and pink-violet-staining
      bands. Individual differences were usually in the size (or density) of the bands,
      not in the number. Repeat sampling of stimulated whole saliva over a period of
      weeks from the same individuals revealed a striking consistency of protein
      patterns, indicating a profound physiological stability of whole saliva. These
      results provide baseline data for whole saliva and suggest its use for future
      studies.

PMID- 8526806
TI  - The effects of sectioning angle on measurements of enamel prism size and spacing.
AB  - Comparative studies of prism size and spacing employ variables that are based on
      idealized, two-dimensional models. Results of modelling experiments illustrate
      that three-dimensional prism orientation can have a significant impact on two
      dimensional measurements. In comparing prism size and spacing variables, it is
      essential to maintain control over the angle at which prisms are sectioned in
      order to compare real differences between taxa rather than preparation artefact.
      The further sectioning angles are from orthogonal, the greater the possibility
      for misrepresenting true prism size and spacing. While the survey of prism
      compression/extension (k) values reported here, as well as those described in
      previous studies, indicate that prism sectioning angles are only rarely extreme
      enough to render other values of prism and ameloblast size and spacing useless,
      the potential influence of sectioning obliquity on variation cannot be dismissed.

PMID- 8526807
TI  - Identification of osteopontin in human dental calculus matrix.
AB  - Osteopontin is a prominent non-collagenous component of bone matrix, although it
      is expressed in several other tissues. Recently, osteopontin was reported to be
      involved in urinary stone formation and atherosclerotic lesions of the aorta,
      suggesting that it may be a key protein associated with these types of
      pathological mineralization. In this study, whether or not human dental calculus
      contains osteopontin was investigated by immunoblotting and immunohistochemical
      analyses. After extraction of calculus proteins with EDTA and separation of the
      proteins by electrophoresis, immunoblotting analysis revealed the presence of
      osteopontin. Two forms of osteopontin appeared at 61 and 68 kDa on 10%
      polyacrylamide gel and the proteins were digested with thrombin, a highly
      specific protease. Moreover, immunohistochemical analysis revealed that
      osteopontin was localized in dental calculus adherent to tooth roots. These
      findings indicate that osteopontin is, in fact, present in human dental calculus
      and may be involved in calculus formation as the stone matrix.

PMID- 8526808
TI  - Detection of binding of denatured salivary alpha-amylase to Streptococcus
      sanguis.
AB  - Native alpha-amylase, either solubilized, or immobilized and tested with an
      overlay immunotechnique, was bound in a species-specific manner to Streptococcus
      mitis and to one of the Streptococcus gordonii strains. However, only
      insignificant amounts of alpha-amylase were bound to Streptococcus sanguis and
      all other strains tested. When alpha-amylase was denatured before immobilization,
      Streptococcus sanguis bound strongly to the protein while binding of other
      strains was insignificant.

PMID- 8526809
TI  - Type VI collagen periodic fibrils in the synovium of the mouse temporomandibular
      joint.
AB  - Immunohistochemical staining with anti-type VI collagen antibody was strongly
      positive in the intimal layer and moderately positive in the subsynovium. After
      treatment with 20 mM ATP, numerous structures with a periodicity of 100 +/- 10 nm
      (type VI collagen fibrils) appeared around the synovial cells. As the periodic
      dark bands were stained by ruthenium red, proteoglycan(s) or glycosaminoglycan(s)
      were probably associated with the type VI collagen fibrils. When the tissue was
      digested with testicular hyaluronidase before ATP treatment, the periodic fibrils
      were not found, and only a filamentous network of 100-nm interval was seen around
      the cells. Thus, type VI collagen is abundant in the synovium of the mouse
      mandibular joint and is associated with proteoglycans or glycosaminoglycans,
      which might have a role in its formation.

PMID- 8526810
TI  - The response of human gingival fibroblasts to interleukin-1 in their metabolic
      conversion of two androgenic substrates.
AB  - The effects of interleukin-1 (IL-1) on the metabolism of two androgenic
      substrates, testosterone and 4-androstenedione, that can be converted to the
      potent anabolic metabolite 5 alpha-dihydrotestosterone (DHT) were studied.
      Duplicate incubations of confluent gingival fibroblasts were made in Eagle's
      minimum essential medium + 10% fetal calf serum, with [14C]-testosterone/[14C]
      androstenedione as initial substrates and optimal stimulatory concentrations of
      IL-1. [14C]-testosterone was converted mainly to DHT and 4-androstenedione. There
      was a 1.8-fold increase in DHT synthesis (n = 7; p < 0.02) and a 1.9-fold
      increase in 4-androstenedione in response to IL-1 (n = 7; p < 0.02) (Wilcoxon
      signed-rank test for non-parametric, paired observations). [14C]-4
      androstenedione was mainly converted to DHT and testosterone. There was a 1.7
      fold increase in DHT synthesis in response to IL-1 (n = 8; p < 0.01), and a 1.5
      fold increase in testosterone formation from [14C]-4-androstenedione in the
      presence of IL-1, in six of the cell lines (n = 6; p < 0.05). Both testosterone
      and 4-androstenedione were effective substrates in forming the potent metabolite
      DHT in significant amounts in response to IL-1. This is significant in view of
      the well-documented effects of androgens on connective tissue and bone matrix,
      and may have implications for the healing potential of lesions in inflammatory
      periodontal disease.

PMID- 8526811
TI  - The effect of ivermectin treatment of late pregnant dairy cows in south-west
      Victoria on subsequent milk production and reproductive performance.
AB  - A total of 498 dairy cows in 5 predominantly pasture-fed herds were allocated to
      pairs. One cow in each pair was treated with a single dose of ivermectin during
      the dry period. Treated and untreated cows were managed as a single group
      throughout the trial. Most cows calved between 45 and 115 days after treatment.
      When data from all herds were pooled, treated cows produced an extra 74 L of mild
      over the first 100 days of the subsequent lactation (95% confidence interval 20
      to 128). Means were greater among treated groups relative to untreated groups in
      all 5 herds. However, when analysed individually, differences were statistically
      significant (P < 0.05) in 1 herd only. Over the complete lactation, mean milk
      volume for treated cows was 86 L greater than for untreated cows (95% confidence
      interval of difference -57 to 229; P = 0.24). Untreated cows produced 2473 L and
      5883 L for the first 100 days of lactation and for the complete lactation,
      respectively. Milk production responses to treatment did not vary significantly
      with parity, body condition score, previous production index, calving date
      category or with plasma pepsinogen concentrations or faecal egg count at the time
      of treatment. Faecal egg counts and plasma pepsinogen concentrations were low at
      the start of the study. The interval from calving to conception was 4.8 days less
      in treated cows (95% confidence interval 1.2 to 8.2) relative to untreated cows
      when data from all 5 herds were pooled. Differences within individual herds were
      not statistically significant.

PMID- 8526812
TI  - Controlling microbial contamination on beef and lamb meat during processing.
AB  - The microbiological quality of carcases, meat and environmental surfaces was
      evaluated in commercial boning rooms processing beef and lamb. There was
      considerable variation in the level of microbial contamination on both carcases
      and meat, with counts ranging from less than 20 to 10(8)/cm2 on carcases and to 2
      x 10(7)/cm2 on meat. The level of microbial contamination on meat was influenced
      by the level of carcase contamination at boning and by the boning process itself.
      Carcase contamination was the major determinant of microbiological quality, as
      more than 70% of carcase had microbial counts greater than 10(3)/cm2. Cutting
      boards were a major source for microbial dissemination during boning,
      particularly when carcase counts were less than 10(3)/cm2. If carcases were
      heavily contaminated, the contamination of processing surfaces was irrelevant in
      determining microbial loads on meat. Where carcase contamination was at low to
      moderate levels, the contribution of the boning process to the contamination on
      meat assumed increased significance. Under these conditions, improved sanitation
      of cutting surfaces in the boning room resulted in a significant reduction in
      microbial contamination on the surface of meat. These results can form the basis
      for ensuring that improvements made in carcase management before boning, to
      improve microbiological quality, will be preserved through attention to cutting
      board hygiene during boning.

PMID- 8526813
TI  - Effect of storage on some constituents of camel serum.
AB  - Effects of storage at room temperature (23-25 degrees C) and refrigeration (4-5
      degrees C) on various biochemical constituents of camel serum were investigated.
      Albumin, globulin, calcium, phosphorus, cholesterol, aspartate aminotransferase
      (AST), alkaline phosphatase (AP) and gamma glutamyltransferase (GGT) did not
      change over 9 days when stored at 4-5 degree C. At 4-5 degree C, creatinine, iron
      and glucose in camel sera remained stable for 6 days; total protein for 7 days;
      and blood urea nitrogen for 8 days. Decreased activities in creatine kinase (CK),
      lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were apparent
      after 1, 6, and 7 days, respectively. At room temperature, total protein,
      albumin, globulin, calcium and phosphorus were stable throughout the 9 days.
      Changes in glucose and iron occurred after 3 days. Stability at room temperature
      for LDH was 1 day; AST, 3 days; GGT and ALT, 6 days; and AP, 8 days. CK activity
      had already declined by 4 hours and by 9 days, only 34% activity remained.

PMID- 8526814
TI  - The use of tiletamine hydrochloride and zolazepam hydrochloride for sedation of
      the mountain brushtial possum, Trichosurus caninus Ogilby (Phalangeridae:
      Marsupialia).
AB  - A combination of tiletamine hydrochloride and zolazepam hydrochloride in a 1:1
      ration by weight was used successfully to sedate mountain brushtail possums,
      Trichosurus caninus, in the field. A standard total dose of 50 to 60 mg provided
      adequate sedation for the completion of a range of handling procedures. We
      describe the induction time, dose rate and side-effects associated with the use
      of tiletamine and zolazepam in T caninus.

PMID- 8526815
TI  - Infection of cattle in Queensland with bluetongue viruses: II. Distribution of
      antibodies.
AB  - A survey of the distribution of serum antibodies to bluetongue viruses in
      Queensland cattle herds was conducted in 1989. A total of 410 herds were selected
      in which sera from 20 or more cattle had been tested with the agar gel
      immunodiffusion (AGID) test. Estimates of prevalence were standardised for age of
      cattle and adjusted using results from serum neutralisation (SN) tests. Spatial
      statistical methods were used to investigate the distribution of these selected
      herds with respect to the prevalence of serum antibodies to bluetongue viruses.
      The mean herd prevalence was 5.2% (95% confidence interval 4.5 to 5.9) and the
      median herd prevalence was 3.5% (95% CI 2.8 to 4.2). Prevalence was highest in
      far north Queensland (17.3%) and lowest in south-west Queensland (0.3%).
      Significant (P < 0.01) clustering of selected herds with respect to prevalence of
      serum antibodies was found. Herds with prevalence of serum antibodies to
      bluetongue viruses above the overall mean herd prevalence were significantly (P <
      0.05) clustered in the north-west, far north and northern and southern coastal
      regions of Queensland. Clustering within the north-west and southern coastal
      regions of Queensland was more pronounced than the clustering detected in the
      northern coastal and far north regions.

PMID- 8526816
TI  - Increased tolerance to annual ryegrass toxicity in sheep given a supplement of
      cobalt.
AB  - To determine whether oral cobalt supplements could modify the clinical onset of
      annual ryegrass toxicity, groups (n = 5) of sheep were dosed orally with 0, 4 or
      16 mg cobalt/day. After 3 weeks on this treatment, toxic ryegrass seed was added
      to their feed to provide 0, 0.15 and 0.30 mg corynetoxins/kg body weight, daily.
      Sheep receiving cobalt ingested 30% more toxin than did unsupplemented sheep
      before clinical signs developed (P = 0.03). There was no significant difference
      between groups receiving 4 and 16 mg cobalt. The results showed that cobalt
      delayed, but did not prevent, the onset of clinical signs of annual ryegrass
      toxicity.

PMID- 8526817
TI  - Electrocardiographic values in Spanish-bred horses of different ages.
AB  - The duration of electrocardiograph wave forms and intervals were determined in
      179 Spanish-bred (Andalusian) horses aged from 1 month to 17 years. The values
      were compared with those of other breeds, and the relationship between
      electrocardiographic data and age was examined. High correlation coefficients
      were found between PR, ST and QT intervals and the age of the horses, and an
      inverted relation between heart rate and age was found. A multiple range analysis
      was made and the results suggest that significant changes in duration values and
      heart rate occurred at the age of 6 months and in the second year of life.

PMID- 8526818
TI  - Squamous cell carcinoma of the pharyngeal wall in a horse.

PMID- 8526819
TI  - The clinical differentiation of nervous and muscular locomotor disorders of sheep
      in Australia.
AB  - Many of the nervous and muscular locomotor disorders that affect sheep throughout
      Australia are commonly referred to as "staggers" syndromes. The range of clinical
      signs displayed by sheep suffering these disorders is sufficiently diverse to
      enable each syndrome to be graded into one of 5 progressive clinical groups. The
      first group, the limb paresis syndromes, includes the primary myopathies
      associated with the ingestion of Ixiolaena brevicompta, Malva parviflora, and
      Trachymene ochracea, as well as selenium and Vitamin E disorders, Paroo virus
      staggers, congenital progressive muscular dystrophy, humpy back, hypocalcaemic
      muscle weakness, Tribulus terrestris staggers and tetanus. The second group is
      characterised by limb paresis with knuckling of the fetlocks, and includes the
      plant-associated toxicities of Romulea rosea, Stachys arvensis, Trachyandra
      divaricata, and Tribulus micrococcus, together with haloxon toxicity, enzootic
      ataxia (copper deficiency), and the probably genetic disorders of segmental
      axonopathy, neuroaxonal dystrophy, and degenerative thoracic myelopathy. Other
      locomotor disorders that fit more loosely into this group are listerial myelitis
      (post-dipping staggers), vitamin A deficiency, cervico-thoracic vertebral
      subluxation Stypandra glauca toxicity, Ipomoea spp toxicity, ivermectin toxicity,
      and botulism. The third group, the falling syndromes, includes the probably
      genetic disorders of thalamic cerebellar neuropathy, cerebellar abiotrophy, and
      globoid cell leucodystrophy, together with Swainsona spp toxicity. The fourth
      group, the falling syndromes, includes the plant associated toxicities of
      phalaris staggers, perennial rye grass staggers and nervous ergotism (Claviceps
      paspali).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526820
TI  - Treatment of ovine dermatophilosis with long-acting oxytetracycline or a
      lincomycin-spectinomycin combination.

PMID- 8526821
TI  - Hydrops foetalis in dwarf calves associated with twinning.

PMID- 8526822
TI  - Pigs and foot-and-mouth disease--deja vu.

PMID- 8526823
TI  - Spontaneous resolution of retained renal calculi in USAF aviators.
AB  - USAF aviators may be granted medical waivers for continued flying duties when
      diagnosed as having retained renal calculi in parenchymal locations or in
      portions of the collecting system from which spontaneous passage is unlikely. The
      USAF Aircrew Medical Waiver File was reviewed in order to determine the
      proportion of USAF aviators with waivers for retained renal calculi whose calculi
      subsequently resolved. Of the 60 currently active aviators granted waivers
      between January 1976 and December 1990, 7 have had their retained calculi resolve
      following surgical intervention, and 13 (21.7%), 95% CI [11.2%, 32.1%], had
      "spontaneous" resolution of their retained calculi. Using the Armstrong
      Laboratory's Aeromedical Consultation Service clinical database, it was possible
      to determine how the diagnoses of retained stones were established and/or
      disestablished in 15 of the 60 aviators. Theories on stone formation and
      resolution, tools employed in diagnosis, and implications of these study findings
      on flight duties are discussed.

PMID- 8526824
TI  - A review of articles published in Aviation, Space, and Environmental Medicine,
      1975-94.
AB  - Aviation, Space, and Environmental Medicine, the official journal of the
      Aerospace Medical Association, is dedicated to serving and supporting all who
      work to solve the problems of living and working in hazardous environments on,
      above, and beneath the earth and sea. This study examines and analyzes the
      characteristics of authors and their articles published in Aviation, Space, and
      Environmental Medicine over a 20-y period, from 1975-94. There were 3562 articles
      meeting inclusion criteria published during this period. Articles were analyzed
      for article length, number of authors per article, country and institution of
      origin, main topic, and educational preparation of authors. The majority of
      articles originated in the United States (68%), followed by England (7%), Canada
      (5%), France (3%), Israel (2%), and Russia/USSR (2%). The number of different
      countries contributing articles increased from 26 countries in the first 5 yr to
      35 countries in the last 5 yr. The content has remained relatively uniform, with
      the most frequent topics being aviation medicine, aerospace physiology,
      environmental medicine, and space medicine. The most infrequent topics were
      health promotion and wellness, occupational health, and aerospace nursing. Over
      85% of articles in which the educational status of authors was known were written
      by authors with a doctorate degree. Most primary authors possessed a doctor of
      medicine (38%) degree, doctor of philosophy (37%) degree, or both (5%). This
      analysis can provide insight into the history and future of aerospace and
      environmental medicine and physiology, since the contents of the Journal clearly
      reflect the interests of individuals working in these fields.

PMID- 8526825
TI  - Magnetic resonance imaging as an aid to the diagnosis and treatment evaluation of
      suspected myocardial sarcoidosis in a fighter pilot.
AB  - We present a case of possible myocardial sarcoidosis suspected by the presence of
      multiorgan sarcoidosis along with cardiac dysrhythmia. The diagnosis of a highly
      probable sarcoid infiltrate was made by magnetic resonance imaging, depicting a
      high intensity mass in the ventricular septum. Following corticosteroid treatment
      the mass disappeared, and remains absent after 3 years followup. Also, only minor
      dysrhythmia has been observed during this period. The aeromedical implications
      are discussed.

PMID- 8526826
TI  - The flight engineer had one of the worst headaches in his life.

PMID- 8526827
TI  - Increased flight surgeon role in military aeromedical evacuation.
AB  - BACKGROUND: Physicians were involved in the development of aeromedical evacuation
      (medevac) and flight surgeons flew as crewmembers on the first U.S. military
      medevac flights. However, since World War II flight surgeons have not been
      routinely assigned to operational medevac units. The aeromedical literature
      addressing the role of physicians in medevac is controversial. Recent
      contingencies involving the U.S. Air Force (USAF) have required the augmentation
      of medevac units with flight surgeons. RECENT CHANGES IN THE EUROPEAN THEATER:
      Beginning in 1992, the United States Air Forces Europe (USAFE) assigned three
      flight surgeons to the medevac squadron. Between 2 February 1993 and 24 March
      1994 USAFE moved 241 patients on 29 missions out of the former Yugoslavia--most
      of these missions had a flight surgeon on the crew. Because advance medical
      information on the status of these patients is often nonexistent, the presence of
      a physician on the crew proved life-saving in some instances. In peacetime
      operations, there has been a recent trend in the European theater for the USAF to
      move more unstable patients. OBSERVED BENEFITS OF PHYSICIANS IN MEDEVAC:
      Dedicated medevac flight surgeons have proven to have the specific experience and
      training to perform effectively in the role of in-flight medical attendant. In
      addition, they are effective in negotiating with referring physicians about the
      urgency of movement, required equipment, the need for medical attendants, etc.
      These flight surgeons also provide medical coverage of transiting patients in the
      Aeromedical Staging Flight (ASF), thus providing needed continuity in the medevac
      system. CONCLUSION: Dedicated medevac flight surgeons fill a unique and valuable
      role in medevac systems. Agencies with medevac units should consider assigning
      flight surgeons to these units.

PMID- 8526828
TI  - Sustaining helicopter pilot performance with Dexedrine during periods of sleep
      deprivation.
AB  - BACKGROUND: Around-the-clock operations often are mandated in combat, but while
      aircraft can function effectively throughout continuous 24-hour periods, aviators
      often cannot because of sleep loss. An efficacious countermeasure in sustained
      operations may be the administration of dextroamphetamine (Dexedrine).
      HYPOTHESIS: Dexedrine will effectively prevent many of the performance problems
      associated with sleep deprivation in helicopter pilots. METHODS: A placebo
      controlled, double blind study was conducted. Six U.S. Army helicopter pilots
      completed five flights in a UH-60 simulator while their performance was
      evaluated. Immediately following each flight, data were collected on
      electroencephalographic (EEG) activity and subjective mood ratings. Testing
      sessions occurred at 0100, 0500, 0900, 1300, and 1700. One hour prior to each of
      the first three flights on drug-administration days, the aviators were given 10
      mg of Dexedrine or placebo. RESULTS: Dexedrine, in comparison to placebo,
      improved aviator simulator control on descents, straight-and-levels, standard
      rate turns, and a left-descending turn. Performance was facilitated most
      noticeably at 0500, 0900, and 1700 (after 22, 26, and 34 hours of continuous
      wakefulness). EEG and mood data showed that alertness was sustained significantly
      by Dexedrine--there was reduced slow-wave EEG activity and improved rating of
      vigor and fatigue. No adverse behavioral or physiological effects were observed.
      CONCLUSIONS: Dexedrine appears to be effective for sustaining helicopter pilot
      performance during short periods of sleep loss without producing adverse side
      effects.

PMID- 8526829
TI  - The role of anaerobic power in human tolerance to simulated aerial combat
      maneuvers.
AB  - The relationships of anaerobic power, blood lactate levels, and selected
      anthropometric measurements to +Gz tolerance were examined in 10 adult males.
      Upper and lower body anaerobic indices were determined by Wingate anaerobic tests
      (WT). Acceleration tolerance was measured as duration time for a simulated aerial
      combat maneuver (SACM) centrifuge profile with alternating 4.5 and 7 +Gz 15-s
      plateaus until exhaustion. Group mean (+/- SD) for SACM duration was 250 +/- 97
      s. Peak blood lactate concentration was 4.9 +/- 1.5 mmol/L and overall rating of
      perceived exertion was 7.4 +/- 2.1 using the Borg Category-Ratio Scale. Group
      mean for WT lower body 30-s mean power (MP, index of anaerobic performance) was
      620 +/- 128 W; peak power (PP, highest 5-s power output) was 851 +/- 169 W. Upper
      body MP and PP were 380 +/- 68 W and 497 +/- 81 W, respectively. SACM duration
      time was positively correlated (p < 0.05) with lower body MP and PP, upper body
      PP, various body circumferences, weight, fat-free body weight, and height; but
      did not correlate with WT power outputs relative to body weight, or with other
      SACM variables. Results suggest that anaerobic power is an important physiologic
      component in SACM tolerance.

PMID- 8526830
TI  - Psychological functioning among members of a small polar expedition.
AB  - BACKGROUND: While depressed mood, insomnia, irritability and impaired cognition
      represent common responses to the physical and psychosocial stressors associated
      with polar environments, wide variations exist in their expression and the degree
      to which they adversely affect the health and performance of polar expeditioners.
      In particular, the process of successful adaptation to polar environments and the
      psychosocial characteristics associated with this process remains poorly
      understood. HYPOTHESIS: Psychosocial characteristics associated with successful
      coping with typical stressors are also associated with successful adaptation in
      polar environments. METHODS: The 4 men and 3 women participating in a 3-week
      scientific expedition in the Canadian High Arctic completed a battery of
      psychological questionnaires, including the Profile of Mood States (POMS), prior
      to their departure to Isachsen, N.W.T. In Isachsen, subjects completed the POMS
      and the Structured Interview Guide for the Hamilton Depression Rating Scale-
      Seasonal Affective Disorders Version (SIGH-SAD) each week. RESULTS: Good
      psychological adjustment was demonstrated by a significant decline in POMS factor
      scores for tension-anxiety (p = 0.005), fatigue (p < 0.0001), and confusion (p =
      0.024) from baseline to Week 3, and a significant decline in SIGH-SAD depressive
      symptoms (p < 0.0001) during Weeks 1-3. This is attributed to high levels of
      paratelic dominance and low levels of neuroticism, and use of planful problem
      solving as a coping strategy more frequently than other coping strategies.
      CONCLUSIONS: Improved psychological functioning among polar expeditioners
      reflects a combination of psychosocial characteristics that facilitate successful
      adaptation to any stressful experience, as well as characteristics specifically
      adaptive for living in polar environments.

PMID- 8526831
TI  - Defining and measuring the "right stuff": neuropsychiatrically enhanced flight
      screening (N-EFS).
AB  - BACKGROUND: United States Air Force (USAF) commanders wish to make better pilot
      selection and cockpit-assignment decisions. Also, some pilots will sustain head
      injuries that will affect their flying careers. The complex and unforgiving
      nature of aviation demands a conservative approach to occupational return after
      neurological insult. Therefore, a neuropsychological assessment is required to
      return to flying. The lack of pre-injury neuropsychological data, however,
      hinders accurate assessment of post-injury functioning. HYPOTHESES: a)
      Psychological data may improve the pilot selection and assignment processes as
      military resources dwindle; and b) baseline intellectual/cognitive data may
      support the scientific basis of aeromedical decision-making. METHODS:
      Neuropsychiatrically Enhanced Flight Screening (N-EFS) attempts to validate the
      Multidimensional Aptitude Battery (MAB), CogScreen, Revised NEO-PI (NEO-PI-R),
      and Personal Characteristics Inventory (PCI) for pilot selection and cockpit
      assignment. N-EFS also measures baseline intelligence (using the MAB) and
      cognitive functioning (using the CogScreen) for comparison purposes if a future
      medical flying waiver is needed after neurological insult. These assessments will
      compare the aviator's postinjury functioning to a personal intellectual
      functioning baseline captured at entry into aviation training. RESULTS: N-EFS
      students are scoring from below average to very superior in intellectual
      assessment. Very preliminary personality testing results suggest few significant
      differences between male and female student pilots, with high extraversion being
      the most striking personality characteristic. DISCUSSION: The wide range of
      intellectual functioning in pilot candidates argues for baseline data collection
      to improve future aeromedical decisions.

PMID- 8526832
TI  - The effect of altitude pre-acclimatization on acute mountain sickness during
      reexposure.
AB  - BACKGROUND: Acclimatization to high altitude appears to prevent acute mountain
      sickness (AMS), as evidenced by a decline in AMS symptoms as acclimatization
      progresses. HYPOTHESIS: We hypothesized that partial retention of acclimatization
      would attenuate the incidence and/or severity of AMS upon reinduction to
      altitude. METHODS: To test this hypothesis 6 male lowlanders returned to sea
      level after the acclimatizing of the 16 d at 4300 m (HA). After 8 d at sea level
      (PA), they were reexposed to 4300 m in a hypobaric chamber for 30 h (RA). AMS
      symptom severity was determined by the AMS-cerebral (AMS-C) scores calculated
      from the daily administration of the Environmental Symptoms Questionnaire during
      HA and RA. RESULTS: The mean AMS-C scores were reduced from 0.6 on HA day 1 (HA1)
      to 0.1 during RA (p < 0.05). Four subjects were "sick" (AMS-C > 0.7) during HA1,
      while only one was "sick" during RA. The % oxyhemoglobin, hemoglobin
      concentration and hematocrit were higher during RA compared to HA1. CONCLUSIONS:
      These results suggest that the retention of acclimatization after 8 d at low
      altitude is sufficient to attenuate AMS upon reinduction to high altitude.

PMID- 8526833
TI  - Evaluation of the Lake Louise acute mountain sickness scoring system in a
      hypobaric chamber.
AB  - This study evaluated the relevance of the Lake Louise acute mountain sickness
      (AMS) scoring system in comparison with other AMS scoring systems. To achieve
      this objective nine subjects were submitted to a 9-hr exposure to hypoxia in a
      hypobaric chamber (altitude 4500-5500 m) that led to the development of AMS. AMS
      was scored at the end of this exposure period both by questionnaires (Hackett AMS
      questionnaire, Lake Louise AMS self-report questionnaire, Environmental Symptoms
      Questionnaire ESQ II and ESQ IV) and by a clinical investigation following the
      Lake Louise AMS clinical and functional AMS assessment. The AMS scores were
      between 0 and 9 for the Hackett AMS score, 0 and 38 for the ESQ II AMS score, 0
      and 13.7 for the ESQ IV AMS score, 0 and 10 for the Lake Louise AMS self-report,
      0 and 2 for the Lake Louise AMS clinical assessment score, and between 0 and 2
      for the Lake Louise functional score. All the AMS questionnaire scores were
      related to the clinical AMS assessment score (p < 0.05) without significant
      differences between them. The Lake Louise AMS self-report score appeared highly
      correlated to other AMS scoring systems (Hackett, ESQ II and ESQ IV) (p < 0.05).
      Suggestions were proposed to improve the sensitivity and the specificity of the
      Lake Louise AMS scoring questionnaire but also the Lake Louise AMS clinical
      assessment. In conclusion, this study suggests the relevance of the Lake Louise
      AMS self-report questionnaire to assess and score AMS with simplicity and
      rapidity.

PMID- 8526834
TI  - Isolated effects of peripheral arm and central body cooling on arm performance.
AB  - BACKGROUND: Whole body cooling impairs manual arm performance. The independent
      contributions of local (peripheral) and/or whole body (central) cooling are not
      known. Therefore, a protocol was developed in which the arm and the rest of the
      body could be independently cooled. METHODS: Biceps temperature (Tmus), at a
      depth of 20 mm, and esophageal temperature (Tes) were measured. Six subjects were
      immersed to the clavicles in a tank (body tank) of water under 3 conditions: 1)
      cold body-cold arm (CB-CA); 2) warm body-cold arm (WB-CA); and 3) cold body-warm
      arm (CB-WA). In the latter two conditions, subjects placed their dominant arm in
      a separate (arm) tank. Water temperature (Tw) in each tank was independently
      controlled. In conditions requiring cold body and/or cold arm, Tw in the
      appropriate tanks was 8 degrees C. In conditions requiring warm body and/or warm
      arm, Tw in the appropriate tanks was adjusted between 29 and 38 degrees C to
      maintain body/arm temperature at baseline values. A battery of 6 tests, requiring
      fine or gross motor movements, were performed immediately before immersion and
      after 15, 45, and 70 minutes of immersion. RESULTS: In CB-CA, Tes decreased from
      an average of 37.2 to 35.6 degrees C and Tmus decreased from 34.6 to 22.0 degrees
      C. In WB-CA, Tmus decreased to 18.1 degrees C (Tes = 37.1 degrees C), and in CB
      WA, Tes decreased to 35.8 degrees C (Tmus = 34.5 degrees C). By the end of
      immersion, there were significant decrements (43-85%) in the performance of all
      tests in CB-CA and WB-CA (p < 0.0002); scores for each test were similar in these
      two conditions. There was no significant change in scores throughout the CB-WA
      condition. In both conditions with arm cooling (i.e., WB-CA and CB-CA), Tmus
      accounted for 85-98% of the variance in all tests. When the core was cooled in
      the CB-WA condition, Tes was significantly correlated to scores in only two tests
      (accounted for 90 and 93% of the variance) although the actual effect was small.
      In the CB-CA condition, partial correlations indicated that Tes accounted for 4
      10% of the variance in scores of 4 tests. CONCLUSIONS: We conclude that cooling
      of the body and/or the arm elicits large decrements in finger, hand and arm
      performance. The decrements are due almost entirely to the local effects of arm
      tissue cooling.

PMID- 8526835
TI  - Magnetic resonance imaging quantitation of changes in muscle volume during 7 days
      of strict bed rest.
AB  - BACKGROUND: Prolonged bed rest results in a loss of leg lean body mass. Previous
      studies using bed rest as a model for microgravity have shown decreases in leg
      mass after 12 and 14 d, 5 and 17 wk. HYPOTHESIS: As magnetic resonance imaging
      (MRI) can provide a precise and non-invasive means of determining muscle volume,
      we sought to determine if changes in leg muscle volume could be detected in bed
      rest periods as short as 7 d. METHODS: Five young, healthy, male volunteers were
      subjected to 7 d of absolute bed rest. Each subject underwent MRI quantitation of
      segmental muscle volumes of the calves and thighs before and after bed rest.
      Eleven (calf) and nine (thigh) contiguous 1-cm thick transaxial images were
      generated over prescribed regions using a Technicare MRI imager with a 0.6T
      superconducting magnet and body coil. Image processing was performed using a
      generalized 8-bit medical image analysis package developed at University of Texas
      Medical Branch. Images were analyzed for muscle and non-muscle volumes (including
      fat, blood vessel, and bone marrow volumes). RESULTS: The MRI quantitation
      demonstrated bed rest-induced significant decreases in segmental thigh muscle
      (approximately 3.0%, p < 0.05) volume. CONCLUSIONS: We conclude that computerized
      image analysis of MRI images provides a sensitive tool capable of detecting leg
      volume changes of as little as 3.0% over a 7-d period of strict bed rest.

PMID- 8526836
TI  - Effects of 28-day head-down tilt with and without countermeasures on lower body
      negative pressure responses.
AB  - This study was performed to determine the effects of 28 d of head-down tilt (HDT)
      (simulated weightlessness) on cardiovascular responses to orthostatic stress
      induced by lower body negative pressure (LBNP) (before, during, and after HDT)
      and +60 degrees head-up tilt (before and after HDT) in 12 subjects. Half of them
      underwent countermeasures (CM) of regular muscular exercise (isometric and
      isokinetic training) and LBNP sessions (-30 mm Hg) as generally performed during
      spaceflight; the other six were a control group (C). The countermeasure effect on
      the orthostatic responses to LBNP and tilt test was assessed by studying the
      changes after HDT in the two groups. Essentially, blood pressure was better
      maintained in group CM in the tilt test after HDT (MBP at the end of the tilt vs.
      baseline value: +16% (CM); -19% (C)). LBNP and muscular exercise may have
      contributed to this improvement. One of the probable contributing factors is the
      relative conservation of plasma volume, at the end of HDT, in group CM (-2.2%),
      compared to group C (-11.2%). Transcranial Doppler (TCD) recordings of middle
      cerebral artery (MCA) velocities permitted indirect evaluation of cerebral blood
      flow changes during the orthostatic tests. MCA velocities decreased significantly
      although slightly (-7 to -12%) during LBNP sessions without changes along the HDT
      showing that the cerebral circulation was well preserved in each group. On the
      other hand, subjects undergoing presyncopal symptoms presented a drop in MCA
      velocities, suggesting a decrease in cerebral blood flow.

PMID- 8526837
TI  - High-peak-power microwave pulses: effects on heart rate and blood pressure in
      unanesthetized rats.
AB  - INTRODUCTION: Exposure sources capable of generating high-peak-power microwave
      pulses, with relatively short pulse widths, have recently been developed. Studies
      of the effect of these sources on the cardiovascular systems of animals have not
      been reported previously. METHODS: We exposed 14 unanesthetized male Sprague
      Dawley rats to 10 high-peak-power microwave pulses generated by a transformer
      energized megawatt pulsed output (TEMPO) microwave source, at frequencies ranging
      from 1.2-1.8 GHz. Peak power densities were as high as 51.6 kW/cm2. At 14 d prior
      to irradiation, the animals were implanted with chronic aortic cannulae. With
      appropriate shielding of the transducer, blood pressure recordings were obtained
      during microwave pulsing. RESULTS: In a preliminary series of exposures at 1.7
      1.8 GHz (peak power density 3.3-6.5 kW/cm2), an immediate but transient increase
      in mean arterial blood pressure (significant) and decrease in heart rate (non
      significant) were observed. A loud noise was associated with each pulse produced
      by the TEMPO; this factor was subsequently attenuated. In a second series of
      exposures at 1.2-1.4 GHz (peak power density 14.6-51.6 kW/cm2), there were no
      significant changes in mean arterial blood pressure or heart rate during
      microwave exposure. CONCLUSIONS: The earlier significant increase in blood
      pressure that occurred during microwave exposure appeared to be related to the
      sharp noise produced by the TEMPO source. After appropriate sound attenuation,
      there were no significant effects of exposure to the microwave pulses.

PMID- 8526838
TI  - China eastern MD-11 mass casualty--expect the unexpected: a case report.
AB  - On April 5, 1993, a China Eastern MD-11 underwent three violent pitch-up
      maneuvers, injuring over 100 passengers. The pilot made an emergency landing at
      3:20 a.m. at Shemya, a tiny Aleutian Island with minimal medical facilities and
      personnel. The author describes their medical response, problems encountered and
      lessons learned.

PMID- 8526839
TI  - Correlation of a missense mutation in the human Secretor alpha 1,2
      fucosyltransferase gene with the Lewis(a+b+) phenotype: a potential molecular
      basis for the weak Secretor allele (Sew).
AB  - A missense mutation (A385 to T), predicting an Ile129 to Phe substitution, in the
      human Secretor alpha 1,2-fucosyltransferase gene was present in double dose in
      Lewis(a+b+) individuals, but not in Lewis(a-b+) individuals. Co-segregation of
      the Lewis(a+b+) phenotype with homozygosity for the mutation was also verified.
      These results yield a potential molecular basis for the weak Secretor allele
      (Sew) accounting for the Lewis(a+b+) phenotype.

PMID- 8526840
TI  - Oxidative release of nitric oxide accounts for guanylyl cyclase stimulating,
      vasodilator and anti-platelet activity of Piloty's acid: a comparison with
      Angeli's salt.
AB  - The decomposition of benzenesulphohydroxamic acid (Piloty's acid; PA) and some of
      its derivatives has been reported to yield nitroxyl ions (NO-), a species with
      potent vasodilator properties. In a previous study we demonstrated that the
      oxidative breakdown of PA results in the formation of nitric oxide (NO) and
      suggested that NO rather than NO- may account for its vasorelaxant properties.
      Using isolated aortic rings in organ baths, we now show that high concentrations
      of cysteine potentiate the vasorelaxant response to PA, whereas responses to
      Angeli's salt (AS), a known generator of NO-, were almost completely inhibited.
      These different behaviours of PA and AS are mirrored by their distinct
      chemistries. By using HPLC it was shown that, at physiological pH and in the
      absence of oxidizing conditions, PA is a relatively stable compound. Direct
      chemical determination of NO, stimulation of soluble guanylyl cyclase, and
      measurement of platelet aggregation under various experimental conditions
      confirmed the requirement for oxidation to release NO from PA, and quite weak
      oxidants were found to be sufficient to promote this reaction. In contrast, at pH
      7.4 AS decomposed rapidly to yield nitrite (NO2-) and NO-, bu did not produce NO
      on reaction with dioxygen (O2) or hydrogen peroxide (H2O2). Thus sulphohydroxamic
      acids are a new class of thiol-independent NO-donors that generate NO rather than
      NO- under physiological conditions.

PMID- 8526841
TI  - Activation of mitogen-activated protein kinase by heat shock treatment in
      Drosophila.
AB  - Heat shock treatment of Drosophila melanogaster tissue culture cells causes
      increased tyrosine phosphorylation of several 44 kDa proteins, which are
      identified as Drosophila mitogen-activated protein (MAP) kinases. Tyrosine
      phosphorylation occurs within 5 min, and is maintained at high levels during heat
      shock. It decreases to basal levels during recovery, concurrent with the
      repression of heat shock transcription and heat-shock-protein synthesis. The
      increased MAP kinase tyrosine phosphorylation is parallelled by increased MAP
      kinase activity. At least two MAP kinases, DmERK-A and DmERK-B, are identified
      whose tyrosine phosphorylation increases during heat shock. Thus MAP kinase
      activation is an immediate early response to heat shock, and its increased
      activity is maintained throughout heat shock treatment. Protracted MAP kinase
      activation may contribute to heat shock transcription factor phosphorylation and
      the numerous metabolic alterations that constitute the heat-shock response.

PMID- 8526842
TI  - Purification of pancreas type-I ATP diphosphohydrolase and identification by
      affinity labelling with the 5'-p-fluorosulphonylbenzoyladenosine ATP analogue.
AB  - The enzyme recently identified as type-I ATP diphosphohydrolase (ATPDase; EC
      3.6.1.5) has been purified from the zymogen granule membrane of pig pancreas.
      After solubilization with Triton X-100 and chromatographies on ion-exchange and
      Affi-Gel Blue columns an approximate 3500-fold purification was obtained. The
      enzyme preparation with a specific activity of 45 units/mg of protein was much
      further purified by PAGE under non-denaturing conditions. The active band
      localized on the gel contained two proteins after SDS/PAGE and silver staining,
      corresponding to apparent molecular masses of 56 and 54 kDa. The identity of the
      ATPDase was confirmed by an affinity labelling technique with 5'-p
      fluorosulphonylbenzoyladenosine (FSBA) as an ATP analogue. The latter was
      detected by a Western blot technique. A strong reaction was observed with the
      band corresponding to 54 kDa. N-terminal sequence analysis revealed that the 56
      kDa protein has significant similarities (50-72%) with lipases, whereas the 54
      kDa enzyme has no significant similarity with any known proteins. N-glycosidase F
      treatment confirmed the glycoprotein nature of the enzyme and suggested that the
      enzyme bears several N-glycosylation sites. Comparisons of molecular masses and
      biochemical properties show that this ATPDase is different from other reported
      mammalian ATPDases.

PMID- 8526843
TI  - Heparin binding to platelet factor-4. An NMR and site-directed mutagenesis study:
      arginine residues are crucial for binding.
AB  - Native platelet factor-4 (PF4) is an asymmetrically associated, homo-tetrameric
      protein (70 residues/subunit) known for binding polysulphated glycosaminoglycans
      like heparin. PF4 N-terminal chimeric mutant M2 (PF4-M2), on the other hand,
      forms symmetric tetramers [Mayo, Roongta, Ilyina, Milius, Barker, Quinlan, La
      Rosa and Daly (1995) Biochemistry 34, 11399-11409] making NMR studies with this
      32 kDa protein tractable. PF4-M2, moreover, binds heparin with a similar affinity
      to that of native PF4. NMR data presented here indicate that heparin (9000 Da cut
      off) binding to PF4-M2, while not perturbing the overall structure of the
      protein, does perturb specific side-chain proton resonances which map to
      spatially related residues within a ring of positively charged side chains on the
      surface of tetrameric PF4-M2. Contrary to PF4-heparin binding models which centre
      around C-terminal alpha-helix lysines, this study indicates that a loop
      containing Arg-20, Arg-22, His-23 and Thr-25, as well as Lys-46 and Arg-49, are
      even more affected by heparin binding. Site-directed mutagenesis and heparin
      binding data support these NMR findings by indicating that arginines more than C
      terminal lysines, are crucial to the heparin binding process.

PMID- 8526844
TI  - Intracellular reactive oxygen species as apparent modulators of heat-shock
      protein 27 (hsp27) structural organization and phosphorylation in basal and
      tumour necrosis factor alpha-treated T47D human carcinoma cells.
AB  - The small stress protein heat-shock protein 27 (hsp27) is an oligomeric
      phosphoprotein, constitutively expressed in most human cells, which enhances
      cellular resistance to tumour necrosis factor alpha (TNF alpha). This phenomenon
      correlates with dramatic changes in hsp27 cellular location, structural
      organization and phosphorylation. To gain a better understanding of the molecular
      mechanisms regulating these properties of hsp27, we investigated whether they
      were a consequence of the intracellular production of reactive oxygen species
      (ROS) generated by TNF alpha. Here, we report that, in T47D carcinoma cell lines,
      the rapid burst of intracellular ROS production and changes in hsp27 locale,
      structural organization and phosphoisoform composition induced by TNF alpha were
      abolished by the overexpression of the antioxidant enzyme seleno-glutathione
      peroxidase (GSHPx). These effects were greatly diminished when GSHPx-expressing
      cells were grown in the absence of selenium, a cofactor that is essential for
      seleno-GSHPx activity, indicating that they are directly linked to the increased
      GSHPx activity. Moreover, in growing T47D cells, GSHPx expression induced
      intracellular redistribution of hsp27 and decreased the phosphorylation of this
      protein without altering its pattern of oligomerization. In contrast, the heat
      mediated phosphorylation of hsp27 was not altered by decreased intracellular ROS
      levels. Hence, in growing and TNF-treated cells, several hsp27 properties appear
      to be modulated by fluctuations in intracellular ROS levels.

PMID- 8526845
TI  - Glial hyaluronate-binding protein: a product of metalloproteinase digestion of
      versican?
AB  - Glial hyaluronate-binding protein (GHAP) is a 60 kDa glycoprotein with an amino
      acid sequence identical to that of the hyaluronate-binding region of versican, a
      large fibroblast aggregating proteoglycan found in the brain. Both GHAP and
      versican were identified by immunoblot in bovine brain extracts prepared only
      minutes after death. Human recombinant collagenase, stromelysin, mouse gelatinase
      and gelatinases isolated from human brain by affinity chromatography digest
      versican and give rise to a polypeptide with electrophoretic mobility identical
      to GHAP. Immunoblot analysis, peptide mapping and C-terminal amino acid
      sequencing indicate that the polypeptide generated by digestion with human brain
      gelatinases is identical to GHAP. We suggest that GHAP is a naturally occurring
      versican degradation product.

PMID- 8526846
TI  - Identification of the ferroxidase centre of Escherichia coli bacterioferritin.
AB  - The bacterioferritin (BFR) of Escherichia coli takes up iron in the ferrous form
      and stores it within its central cavity as a hydrated ferric oxide mineral. The
      mechanism by which oxidation of iron (II) occurs in BFR is largely unknown, but
      previous studies indicated that there is ferroxidase activity associated with a
      site capable of forming a dinuclear-iron centre within each subunit [Le Brun,
      Wilson, Andrews, Harrison, Guest, Thomson and Moore (1993) FEBS Lett. 333, 197
      202]. We now report site-directed mutagenesis experiments based on a putative
      dinuclear-metal-ion-binding site located within the BFR subunit. The data reveal
      that this dinuclear-iron centre is located at a site within the four-alpha
      helical bundle of each subunit of BFR, thus identified as the ferroxidase centre
      of BFR. The metal-bound form of the centre bears a remarkable similarity to the
      dinuclear-iron sites of the hydroxylase subunit of methane mono-oxygenase and the
      R2 subunit of ribonucleotide reductase. Details of how the dinuclear centre of
      BFR is involved in the oxidation mechanism were investigated by studying the
      inhibition of iron (II) oxidation by zinc (II) ions. Data indicate that zinc (II)
      ions bind at the ferroxidase centre of apo-BFR in preference to iron (II),
      resulting in a dramatic reduction in the rate of oxidation. The mechanism of iron
      (II) oxidation is discussed in the light of this and previous work.

PMID- 8526847
TI  - The T-tubule is a cell-surface target for insulin-regulated recycling of membrane
      proteins in skeletal muscle.
AB  - (1) In this study we have determined the distribution of various membrane
      proteins involved in insulin-activated glucose transport in T-tubules and in
      sarcolemma from rat skeletal muscle. Two independent experimental approaches were
      used to determine the presence of membrane proteins in T-tubules: (i) the
      purification of T-tubules free from sarcolemmal membranes by lectin
      agglutination, and (ii) T-tubule vesicle immunoadsorption. These methods
      confirmed that T-tubules from rat skeletal muscle were enriched with
      dihydropyridine receptors and tt28 protein and did not contain the sarcolemmal
      markers dystrophin or beta 1-integrin. Both types of experiments revealed an
      abundant content of GLUT4 glucose carriers, insulin receptors and SCAMPs
      (secretory carrier membrane proteins) in T-tubule membranes. (2) Acute
      administration in vivo of insulin caused an increased abundance of GLUT4 in T
      tubules and sarcolemma. On the contrary, insulin led to a 50% reduction in
      insulin receptors present in T-tubules and in sarcolemma, demonstrating that
      insulin-induced insulin receptor internalization affects T-tubules in the muscle
      fibre. The alteration in the content of GLUT4 and insulin receptors in T-tubules
      was a consequence of insulin-induced redistribution of these proteins. SCAMPs
      also redistributed in muscle membranes in response to insulin. They were
      recruited by insulin from intracellular high-density fractions to intracellular
      lighter-density fractions and to the cell surface, showing a pattern of insulin
      induced cellular redistribution distinct from those of GLUT4 and the insulin
      receptor. (3) In conclusion, the T-tubule is a cell-surface target for membrane
      proteins involved in recycling such as SCAMPs or for membrane proteins that
      acutely redistribute in response to insulin such as GLUT4 or insulin receptors.

PMID- 8526848
TI  - Characterization of human AMP deaminase 2 (AMPD2) gene expression reveals
      alternative transcripts encoding variable N-terminal extensions of isoform L.
AB  - AMP deaminase (AMPD) is a highly regulated enzymic activity and multiple isoforms
      of this enzyme are coded for by a multigene family in mammalian species,
      including man. Isoform L (liver) is the main activity present in adult human
      liver and is the protein product of the AMPD2 gene, which is widely expressed in
      non-muscle tissues and cells. A previous report described almost the full-length
      cDNA sequence and part of the human AMPD2 gene and also presented Northern blot
      evidence for multiple transcripts in brain. This study was performed to further
      characterize the AMPD2 gene and its expression in human tissues. AMPD2 genomic
      and human cerebellum cDNA clones were isolated, sequenced and used as probes in
      RNase protection analyses which together demonstrated the following: (1) an
      intervening sequence near the 5'-end of the published AMPD2 cDNA, which affects
      the predicted N-terminal amino acid sequence of isoform L; (2) alternative
      transcripts resulting from exon shuffling at, or near, the 5'-end of the AMPD2
      gene that exhibit tissue-specific patterns of relative abundance; (3) predicted
      usage of three different initiation codons to confer variable N-terminal
      extensions on isoform L polypeptides; and (4) an extension of a 3' untranslated
      sequence in some AMPD2 transcripts. In addition, reverse transcriptase PCR and
      additional RNase protection analyses were used to map the 5'-ends of two mutually
      exclusive exon 1 sequences, both of which contain multiple transcription
      initiation sites. These results are discussed in relation to predicted isoform L
      diversity across human tissues and cells.

PMID- 8526849
TI  - Alkylphosphocholines inhibit choline uptake and phosphatidylcholine biosynthesis
      in rat sympathetic neurons and impair axonal extension.
AB  - At least 50% of the major axonal membrane lipid, phosphatidylcholine, of rat
      sympathetic neurons is synthesized in situ in axons [Posse de Chaves, Vance,
      Campenot and Vance (1995) J. Cell Biol. 128, 913-918]. In the same study we
      reported that, in a choline-deficient model for neuron growth,
      phosphatidylcholine synthesis in cell bodies is neither necessary nor sufficient
      for growth of distal axons. Rather, the local synthesis of phosphatidylcholine in
      distal axons is required for normal axon growth. We have now used three
      alkylphosphocholines (hexadecylphosphocholine, dodecylphosphocholine and
      octadecylphosphocholine) as inhibitors of PtdCho biosynthesis in a compartmented
      model for culture of rat sympathetic neurons. The experiments reveal that
      alkylphosphocholines decrease the uptake of choline into these neurons and
      inhibit PtdCho synthesis, but not via an effect on the activity of the enzyme
      CTP: phosphocholine cytidylyltransferase. We also show that when the distal
      axons, but not the cell bodies, are exposed to alkylphosphocholines, axonal
      elongation is inhibited, which is consistent with the hypothesis that
      phosphatidylcholine synthesis in axons, but not in cell bodies, is required for
      axonal elongation. The inhibitory effect of alkylphosphocholines on axon growth
      is most likely not mediated via a decrease in the activity of protein kinase C,
      since when this enzyme activity is down-regulated by treatment of the cells with
      phorbol ester, the alkylphosphocholines retain their ability to inhibit axonal
      growth.

PMID- 8526850
TI  - Involvement of tyrosine kinases in the induction of cyclo-oxygenase-2 in human
      endothelial cells.
AB  - In addition to a constitutive cyclo-oxygenase (Cox-1), human endothelial cells
      also possess an inducible cyclo-oxygenase (Cox-2) which plays an important role
      in the regulation of the synthesis of prostacyclin (prostaglandin I2). Cox-2 is
      regulated and expressed in large quantities upon activation of the cells by
      inducers such as phorbol myristate acetate (PMA), an activator of protein kinase
      C (PKC), or interleukin-1 alpha. We have investigated the involvement of protein
      tyrosine kinases in Cox-2 expression by human endothelial cells upon activation
      by these inducers. PMA or interleukin-1 alpha provoke an increase in the
      phosphorylation of substrates of 110 and 120 kDa and additional phosphorylations
      for a broad band of multiple substrates in the 70 kDa range. This stimulation was
      accompanied by the induction of Cox-2 protein, detectable after stimulation for 1
      h, which is consistent with an increase in activity reflected by prostacyclin
      synthesis; no variation in the expression of Cox-1 could be observed. Three
      distinct inhibitors of protein tyrosine kinases, genistein, herbimycin or AG-213,
      reduced tyrosine phosphorylation of cell substrates, consistently with their
      pharmacological effects. Under these conditions, there was selective reduction of
      Cox-2 expression without modification of Cox-1. Regulation of Cox-2 induction is
      also dependent on the activation of PKC since Ro 31-8220 or PKC depletion by PMA
      prevented its induction. Our results suggest that within the time-frame of our
      experiments these effects on kinases are specific for Cox-2 rather than Cox-1.

PMID- 8526851
TI  - Stimulation of phosphatidylcholine biosynthesis in mouse MLE-12 type-II cells by
      conditioned medium from cortisol-treated rat fetal lung fibroblasts.
AB  - Treatment of murine adult MLE-12 type-II and fetal-rat type-II cells with fetal
      rat-fibroblast-conditioned medium (FFCM) resulted in a 2-fold stimulation of
      [14C]choline incorporation into phosphatidylcholine. Soluble CTP:phosphocholine
      cytidylyltransferase (CT) activity was increased approx. 3-fold in FFCM-treated
      fetal-rat type-II cells but was not changed in MLE-12 cells. Neither choline
      kinase nor cholinephosphotransferase activities were affected by treatment of MLE
      12 cells with FFCM. Long-term labelling of MLE-12 cells with [14C]choline,
      followed by a 14-18 h chase with FFCM, resulted in a 2.5-fold decrease in
      [14C]phosphocholine levels relative to controls, suggesting that CT was being
      activated. In contrast, oleate treatment increased CT activity in the particulate
      fraction in both cells. Western blots indicate that soluble CT undergoes
      dephosphorylation in response to FFCM, but no translocation to the particulate
      fraction was noted. Treatment with oleate stimulated a marked translocation.
      Tryptic phosphopeptide maps from FFCM-treated cells revealed only minor
      alterations in the phosphorylation pattern. It is concluded that FFCM and oleate
      activate CT through different mechanisms. The results are consistent with FFCM
      activating CT in MLE-12 as well as fetal type-II cells. However, the reason why
      this activation cannot be detected in vitro is not known.

PMID- 8526852
TI  - Locally formed dopamine modulates renal Na-Pi co-transport through DA1 and DA2
      receptors.
AB  - The involvement of dopamine (DA) receptor subtypes in regulation of renal
      phosphate transport by DA, either exogenous or locally synthesized from L
      dihydroxyphenylalanine (L-dopa) was evaluated in opossum kidney (OK) cells with
      proximal tubular phenotype. DA synthesis from L-dopa by OK cells was abolished by
      carbidopa and benserazide, two dissimilar inhibitors of aromatic L-amino acid
      decarboxylase. L-Dopa stimulated cyclic AMP generation and inhibited Na-dependent
      Pi uptake, and these effects were abolished by carbidopa and benserazide. The
      effects of L-dopa or DA on cyclic AMP generation and on Na-Pi co-transport were
      mimicked by SKF 38393, a DA1 receptor agonist, and were potentiated by S
      sulpiride, a DA2 receptor antagonist. Bromocriptine, a DA2 receptor agonist,
      blunted in a pertussis toxin-dependent manner parathyroid hormone (PTH)-induced
      cyclic AMP generation and inhibition of Pi uptake. In contrast with PTH, neither
      L-dopa nor DA affected significantly the cytosolic calcium concentration. These
      results support the involvement of DA1 and DA2 receptors, positively and
      negatively coupled into adenylate cyclase respectively, in modulation of renal
      phosphate transport.

PMID- 8526853
TI  - The lux autoinducer-receptor interaction in Vibrio harveyi: binding parameters
      and structural requirements for the autoinducer.
AB  - To assess the binding parameters and the structure-function relationship of the
      Vibrio harveyi lux autoinducer, N-(D-3-hydroxybutanoyl)homoserine lactone (D
      HBHL), to light emission, a series of acylhomoserine lactone analogues were
      synthesized and their effects on the stimulation of luminescence of an
      autoinducer-deficient mutant of V. harveyi, D1, examined. Of the analogues with 3
      hydroxyacyl chains, only N-(3-hydroxyvaleryl)homoserine lactone (HVHL) could act
      as an inducer, with about 85% of the potency of D-HBHL in stimulation of
      luminescence; the apparent Kd of the putative receptor for HVHL was 3.8 microM,
      close to that for the natural autoinducer (1.4 microM). Analogues with longer 3
      hydroxyacyl chains, N-(3-hydroxyhexanoyl)homoserine lactone and N-(3
      hydroxyheptanoyl)homoserine lactone, acted as competitive inhibitors of HBHL with
      apparent KI values of 77 and 53 microM respectively. Replacement of the 3
      hydroxybutanoyl moiety with a 3-methylbutanoyl or 3-methoxybutanoyl group created
      weak competitive inhibitors, N-(isovaleryl)- and N-(3-methoxybutanoyl)-
      homoserine lactones, with apparent KI values of 150 and 360 microM respectively.
      Two other analogues, N-(2-hydroxybutanoyl)- and N-(4-hydroxybutanoyl)-homoserine
      lactone, could neither stimulate nor inhibit luminescence. The approach used in
      these studies to demonstrate binding of autoinducer analogues at the same site,
      as well as measurement of the relative dissociation constant, may be of value in
      analysing analogues activating or inhibiting luminescence and other processes
      that are under control of acylhomoserine lactone autoregulators.

PMID- 8526854
TI  - Effect of deoxycholate on guanine-nucleotide-dependent carbachol stimulation of
      phosphoinositidase C in mouse brain cortical membranes.
AB  - Demonstration of guanine-nucleotide-dependent neurotransmitter stimulation of
      phosphoinositide breakdown in brain membranes has generally required the presence
      of the detergent, deoxycholate (DOC), in the assay medium. In the present study,
      by using mouse brain cortical membranes labelled with [3H]inositol in the
      presence of CMP through the reverse PtdIns synthase reaction, we have been able
      to show guanosine 5'-[gamma-thio]triphosphate (GTP[S])-dependent carbachol (CCh)
      stimulation of the formation of [3H]inositol phosphates in the absence of DOC and
      have studied how the detergent affects the response. The results of our study
      indicate that DOC affects the muscarinic receptor-G-protein-phosphoinositidase C
      (PIC) transduction system in several ways. First, it enhances agonist-induced PIC
      activity towards [3H]PtdInsP and [3H]PtdInsP2 and, secondly, it decreases the
      potency for GTP[S] stimulation of PIC, thus enhancing the agonist-induced
      leftward shift of the dose-response curve for GTP[S]. Additionally, DOC appears
      to increase the activity of the enzymes of the phosphoinositide cycle, PtdIns 4
      kinase, Ins(1,4,5)P3 5-phosphatase and Ins(1,4)P2 1-phosphatase, thus altering
      the proportion of phosphoinositide substrates and inositol phosphate products.
      These observations advise caution in drawing conclusions about PIC substrate
      specificity and the potency of both guanine nucleotides and agonists from
      experiments performed in membranes in the presence of DOC or related bile salts.

PMID- 8526855
TI  - An investigation of the membrane topology of the ionotropic glutamate receptor
      subunit GluR1 in a cell-free system.
AB  - We have utilized cell-free translation in rabbit-reticulocyte lysate supplemented
      with canine pancreatic microsomal membranes to study the processing and membrane
      topology of the rat ionotropic glutamate receptor subunit GluR1. In vitro
      synthesized RNA encoding GluR1 was translated to yield a primary translation
      product with an apparent molecular mass of 99 kDa. In the presence of microsomal
      membranes this protein was processed to give a band of 107 kDa. Treatment with
      peptide-N-glycosidase F showed that this increase in molecular mass was due to N
      linked glycosylation. Incubation of the processed receptor with proteinase K
      revealed the presence of a 68 kDa protease-resistant band which decreased to 56
      kDa following deglycosylation. A deletion mutant (GluR1M1) lacking the predicted
      transmembrane domains was fully translocated across the microsomal membrane and
      protected from the action of the protease. The mutant and wild-type receptor
      could be immunoprecipitated by anti-peptide antibodies directed against the C
      terminus. Following translocation of the wild-type and mutant receptor across the
      microsomal membrane and treatment with proteinase K the antibody binding to GluR1
      was abolished, but was retained for GluR1M1. These data allow identification of
      the orientation of the N- and C-termini of GluR1 within the microsome; results
      which are consistent with an extracellular N-terminal and intracellular C
      terminal localization following incorporation into the plasma membrane.

PMID- 8526856
TI  - Activation of P2z purinoceptors diminishes the muscarinic cholinergic-induced
      release of inositol 1,4,5-trisphosphate and stored calcium in rat parotid acini.
      ATP as a co-transmitter in the stimulus-secretion coupling.
AB  - The effect of extracellular ATP on the intracellular free Ca2+ concentration
      ([Ca2+]i) and inositol phosphate production following stimulation with the
      muscarinic cholinergic agonist acetylcholine (ACh) was investigated in isolated
      rat parotid acinar cells. Stimulation of rat parotid acinar cells with ATP4-
      results in a rise in [Ca2+]i that is due to influx of extracellular Ca2+ and
      mobilization of Ca2+ from intracellular stores. Stimulation with purinergic
      agonists revealed that both influx as well as Ca2+ release from intracellular
      stores was mediated through activation of P2z receptors. The Ca2+ mobilization
      from intracellular stores was due to production of Ins(1,4,5)P3 and was inhibited
      by U73122, an inhibitor of phospholipase C-coupled processes. Under Ca(2+)-free
      conditions ATP4- caused a dose-dependent inhibition (IC50 = 8 microM) of the ACh
      evoked Ca2+ release. The inhibitory effect of ATP4- is due to activation of the
      P2z purinoceptors, which results in a strong reduction in the ACh-induced
      inositol phosphate production. Prestimulation with 100 microM ATP4- reduced the
      amount of Ins(1,4,5)P3 formed after maximal ACh stimulation by 91%. In
      conclusion, the inhibitory effect of ATP4- on the ACh-mediated response is due to
      interactions of the activated P2z receptor with the phospholipase C-coupled
      processes underlying the muscarinic cholinergic response.

PMID- 8526857
TI  - Glutathionylspermidine metabolism in Escherichia coli.
AB  - Intracellular levels of glutathione and glutathionylspermidine conjugates have
      been measured throughout the growth phases of Escherichia coli.
      Glutathionylspermidine was present in mid-log-phase cells, and under stationary
      and anaerobic growth conditions accounted for 80% of the total glutathione
      content. N1,N8-bis(glutathionyl)spermidine (trypanothione) was undetectable under
      all growth conditions. The catalytic constant kcat/Km of recombinant E. coli
      glutathione reductase for glutathionylspermidine disulphide was approx. 11,000
      fold lower than that for glutathione disulphide. The much higher catalytic
      constant for the mixed disulphide of glutathione and glutathionylspermidine (11%
      that of GSSG), suggests a possible explanation for the low turnover of
      trypanothione disulphide by E. coli glutathione reductase, given the apparent
      lack of a specific glutathionylspermidine disulphide reductase in E. coli.

PMID- 8526858
TI  - Disruption of GLUT1 glucose carrier trafficking in L6E9 and Sol8 myoblasts by the
      phosphatidylinositol 3-kinase inhibitor wortmannin.
AB  - In this study we have used wortmannin, a highly specific inhibitor of
      phosphatidylinositol (PI) 3-kinase, to assess the role of this enzyme on GLUT1
      glucose carrier distribution and glucose transport activity in myoblasts from two
      skeletal-muscle cell lines, L6E9 and Sol8. As detected in L6E9 cells, myoblasts
      exhibited basal and insulin-stimulated PI 3-kinase activities. Incubation of
      intact myoblasts with wortmannin resulted in a marked inhibition of both basal
      and insulin-stimulated PI 3-kinase activities. L6E9 and Sol8 myoblasts showed
      basal and insulin-stimulated glucose transport activities, both of them inhibited
      by wortmannin in a dose-dependent manner (IC50 approximately 10-20 nM).
      Concomitantly, immunofluorescence analysis revealed that 1 h treatment with
      wortmannin led to a dramatic intracellular accumulation of GLUT1 carriers (the
      main glucose transporter expressed in L6E9 and Sol8 myoblasts) in both cell
      systems. The effect of wortmannin on GLUT1 cellular redistribution was
      independent of the presence of insulin. The cellular distribution of two
      structural plasma-membrane components such as beta 1-integrin or the alpha 1
      subunit of the Na(+)-K(+)-ATPase were unaffected by wortmannin in both the
      absence and the presence of insulin. As a whole, our results indicate that PI 3
      kinase is necessary to basal and insulin-stimulated glucose transport in L6E9 and
      Sol8 myoblasts. Moreover, immunofluorescence assays suggest that in both cellular
      models there is a constitutive GLUT 1 trafficking pathway (independent of
      insulin) that involves PI 3-kinase and which, when blocked, locks GLUT1 in a
      perinuclear compartment.

PMID- 8526859
TI  - The inhibition of pyruvate transport across the plasma membrane of the
      bloodstream form of Trypanosoma brucei and its metabolic implications.
AB  - The pyruvate produced by glycolysis in the bloodstream form of the trypanosome is
      excreted into the host bloodstream by a facilitated diffusion carrier. The
      sensitivity of pyruvate transport for alpha-cyano-4-hydroxycinnamate and the
      compound UK5099 [alpha-cyano-beta-(1-phenylindol-3-yl)acrylate], which are known
      to be selective inhibitors of pyruvate (monocarboxylate) transporters present in
      mitochondria and the plasma membrane of eukaryotic cells, was examined. The
      trypanosomal pyruvate carrier was found to be rather insensitive to inhibition by
      alpha-cyano-4-hydroxycinnamate (Ki = 17 mM) but could be completely blocked by
      UK5099 (Ki = 49 microM). Inhibition of pyruvate transport resulted in the
      retention, and concomitant accumulation, of pyruvate within the trypanosomes,
      causing acidification of the cytosol and osmotic destabilization of the cells.
      Our results indicate that this physiological state has serious metabolic
      consequences and ultimately leads to cell death; thereby identifying the pyruvate
      carrier as a possible target for chemotherapeutic intervention.

PMID- 8526860
TI  - Oxidized glutathione decreases luminal Ca2+ content of the endothelial cell
      ins(1,4,5)P3-sensitive Ca2+ store.
AB  - The model oxidant, t-butyl hydroperoxide (t-buOOH), inhibits Ins(1,4,5)P3
      dependent Ca2+ signalling in calf pulmonary artery endothelial cells. Metabolism
      of t-buOOH within the cytosol is coupled to the oxidation of glutathione. In this
      study, we investigated whether oxidized glutathione (GSSG) is the intracellular
      moiety responsible for mediating the effects of t-buOOH on Ca2+ signalling. The
      increase in cytosolic [Ca2+] stimulated by application of 2,5-di-t
      butylhydroquinone (BHQ) was used to estimate the luminal Ca2+ content of the
      Ins(1,4,5)P3-sensitive store in intact cells. Luminal Ca2+ content was unaffected
      by t-buOOH (0.4 mM, 0-3 h) unless intracellular GSSG content was concomitantly
      elevated. The effect was specific for increased GSSG and was not replicated by
      depletion of GSH. These results suggest that cytosolic GSSG, produced
      endogenously within the endothelial cell, decreases the luminal Ca2+ content of
      Ins(1,4,5)P3-sensitive Ca2+ stores. Depletion of internal Ca2+ stores by GSSG may
      represent a key mechanism by which some forms of oxidant stress inhibit signal
      transduction in vascular tissue. At the plasma membrane, t-buOOH is known to
      inhibit the capacitative Ca2+ influx pathway. Increased intracellular GSSG
      potentiated the inhibitory effect of t-buOOH on Ca2+ influx, thereby providing
      the first evidence that activity of the capacitative Ca2+ influx channel is
      sensitive to thiol reagents formed endogenously within the cell.

PMID- 8526861
TI  - Binding of the proline-rich region of the epithelial Na+ channel to SH3 domains
      and its association with specific cellular proteins.
AB  - The amiloride-sensitive epithelial Na+ channel (ENaC) is an important component
      of the Na(+)-reabsorption pathway in many epithelia. The identification of three
      subunits of ENaC (alpha, beta and gamma), as well as results from a number of
      functional and biochemical studies, suggests that functional Na+ channels are
      composed of a complex of proteins. To learn about possible interactions of the
      channel with other proteins, we studied the alpha-subunit of rat and human ENaC.
      We found that the proline-rich C-terminal domains of both rat and human alpha
      ENaC, expressed as glutathione S-transferase fusion proteins, bound to SH3
      domains in vitro. A 116 kDa protein from a human lung adenocarcinoma cell line
      (H441) was specifically bound by the human alpha-ENaC C-terminal fusion protein
      and by a shorter 18-amino acid proline-rich peptide derived from the larger
      fusion protein. The 116 kDa protein was not glycosylated and was not
      phosphorylated on tyrosine or by cyclic AMP-dependent protein kinase (PKA). A 134
      kDa protein which was also bound by the human alpha-ENaC C-terminal fusion
      protein was a substrate for phosphorylation by PKA. These data suggest that the
      proline-rich C-terminal tail of alpha-ENaC may interact with other proteins that
      control its function, regulation or localization.

PMID- 8526862
TI  - Purification and characterization of the human type 1 Ins(1,4,5)P3 receptor from
      platelets and comparison with receptor subtypes in other normal and transformed
      blood cells.
AB  - We report the first purification of a native human form of the Ins(1,4,5)P3
      (InsP3) receptor. This receptor, isolated from platelets, has an apparent
      molecular mass on SDS/PAGE of 252 kDa and is chromatographed by gel filtration as
      an oligomer of about 1 x 10(6) kDa. [3H]InsP3 bound to a single class of sites on
      the purified receptor protein with a Kd of 27 nM and a Bmax. of 2.2 nmol/mg of
      protein. The platelet InsP3 receptor, like the rodent cerebellar receptors, was
      identified immunochemically as a type 1 receptor, but unlike its brain
      counterparts bound poorly to concanavalin A and other lectins and was not
      significantly phosphorylated by protein kinase A. All cultured megakaryocytic
      leukaemia cell lines (e.g. Dami, CHRF-288 and Meg-01) and HEL cells were also
      immunopositive for type 1 receptor, which was substantially increased in some
      cases by DMSO or phorbol 12-myristate 13-acetate (PMA) which induce further
      megakaryocytic differentiation. Normal mixed lymphocyte and granulocyte fractions
      and an enriched T-cell fraction from human blood had measurable InsP3-binding
      activity, but no detectable type 1 protein. In contrast, Jurkat E6-1 (T-cell
      lymphoma) cells and the transformed B-cell line RPMI 8392 were immunopositive for
      type 1 receptor. HL-60 (human promyelocytic leukaemia) cells had no detectable
      type 1 receptor unless they were stimulated to differentiate along
      monocyte/macrophage lines by PMA. We conclude that: (1) of the major normal blood
      cells only platelets contain type 1 InsP3 receptors; (2) some neoplastic
      transformed blood cell lines also express type 1 receptors, in contrast to their
      normal counterparts; and (3) increased levels of type 1 InsP3 receptor are
      induced in some transformed cells under conditions that favour their further
      terminal differentiation.

PMID- 8526863
TI  - Two different isoschizomers of the type-II restriction endonuclease Taq I (T/CGA)
      within the same Thermus isolate: Tsp32 I, an enzyme with similar heat stability
      properties to the prototype enzyme Taq I, and Tsp32 II, a hyperthermostable
      isoschizomer of Taq I.
AB  - We have recently screened 112 separate isolates of the genus Thermus, collected
      from neutral and alkaline hot water springs on four continents, for the presence
      of the Type-II restriction endonuclease Taq I (T/CGA). One particular isolate
      from the Azores (strain 32) was found to contain high levels of a restriction
      endonuclease with the same recognition and cleavage site as Taq I. Initial
      studies revealed that the partially purified enzyme from strain 32 was
      considerably more resistant to heat inactivation than the prototype enzyme Taq I,
      being able to withstand temperatures at least 10 degrees C higher than Taq I,
      before showing evidence of heat inactivation. Subsequently it became clear that
      the partially purified extract from strain 32 contains two separate enzymes, both
      of which are isoschizomers of Taq I. One of the enzymes, Tsp32 I, has similar
      thermal stability characteristics to Taq I, whereas the second Taq I
      isoschizomer, Tsp32 II, found in the same Thermus isolate as Tsp32 I, is
      considerably more thermostable than Taq I, retaining full enzyme activity up to a
      temperature of 85 degrees C. Tsp32 I and Tsp32 II were further distinguished by
      virtue of their different requirements for magnesium ions.

PMID- 8526864
TI  - Protease-susceptible sites and properties of fragments of aortic smooth-muscle
      myosin.
AB  - We have examined the protease susceptibility of aortic myosin, the thermal
      unfolding profiles of myosin rod and light meromyosin (LMM) and the solubility
      properties of the LMM fragments. Two major protease-susceptible sites were found,
      located at the head-rod junction and the heavy meromyosin (HMM)-LMM junction.
      Both tryptic and chymotryptic digestion of aortic myosin rod produced the LMM (80
      85 kDa) and short subfragment 2 (S-2) (40-45 kDa) segments, which were similar to
      those of gizzard myosin rod and differed from the short LMM (70 kDa) and long S-2
      (58 kDa) segments produced from skeletal-muscle rod. The thermal unfolding
      profile of aortic myosin rods exhibited three helix-unfolding transitions, at
      47.5, 51 and 54 degrees C, similar to those of gizzard rods yet different from
      those of skeletal-muscle rods. There was a dramatic difference in the solubility
      of aortic LMM fragments of various molecular mass, as for gizzard smooth-muscle
      LMM and rabbit skeletal-muscle LMM. LMM fragments of molecular mass 77 kDa or
      more were completely insoluble in low-ionic-strength buffer, whereas LMM
      fragments of molecular mass 73 kDa or less were completely soluble in low-ionic
      strength buffer. Proteolytic digestion patterns of LMM showed two additional
      protease-susceptible sites located 13 and 30 kDa from the ends of the LMM
      molecule. This suggests the existence of flexible regions within the LMM
      molecule, which may be responsible for the folded form of aortic myosin.

PMID- 8526865
TI  - Purification and properties of a monoacylglycerol lipase in human erythrocytes.
AB  - A membrane-bound monoacylglycerol lipase (MAGL) activity, previously demonstrated
      in intact human erythrocytes [Boyer, Somma, Verine, L'Hote, Finidori, Merger and
      Arnaud (1981) J. Clin. Endocrinol. Metab. 53, 143-148], has now been purified to
      apparent homogeneity by a five-step procedure involving solubilization in CHAPS
      and sequential chromatographies on Sephacryl S-400, DEAE-Trisacryl, Zn(2+)
      chelating Sepharose and Superose 12 columns. The purified protein has a molecular
      mass of 68 +/- 2 kDa, as determined by SDS/PAGE and gel filtration, suggesting
      that the enzyme behaves as a monomer. The concentration-dependence of MAGL
      activity with monooleoylglycerol, the preferred substrate showed kinetics typical
      of an interfacial lipolytic enzyme displaying optimal activity on emulsified
      substrate particles; apparent Km values were 0.27 mM and 0.49 mM for the sn-1(3)-
      and sn-2-isomers respectively. MAGL had no, or negligible, activity towards tri
      oleoylglycerol, di-oleoylglycerol, oleoylcholesterol, oleoyl-CoA and
      phosphatidylcholine; it was inhibited by di-isopropylfluorophosphate, PMSF and
      diethyl p-nitrophenyl phosphate, suggesting that MAGL is a serine hydrolase. MAGL
      activity was not modified by bile salt or apolipoprotein C-II, whereas a dose
      dependent inhibition was observed with apolipoprotein A-I.

PMID- 8526866
TI  - Altering kinetic mechanism and enzyme stability by mutagenesis of the dimer
      interface of glutathione reductase.
AB  - In wild-type glutathione reductase from Escherichia coli residues Val421 and
      Ala422 are located in an alpha-helix in a densely packed and hydrophobic region
      of the dimer interface, with their side chains packed against those of residues
      Ala422' and Val421' in the second subunit. A series of mutant glutathione
      reductases was constructed in which the identities of the residues at positions
      421 and 422 were changed. Mutations were designed so as to present like charges
      (mutants Val421-->Glu:Ala422-->Glu and Val421-->Lys:Ala422-->Lys) or opposite
      charges (mutant Val421-->Lys:Ala422-->Glu) across the dimer interface to assess
      the role of electrostatic interactions in dimer stability. A fourth mutant
      (Val421-->His:Ala422-->His) was also constructed to investigate the effects of
      introducing a potentially protonatable bulky side chain into a crowded region of
      the dimer interface. In all cases, an active dimeric enzyme was found to be
      assembled but each mutant protein was thermally destabilized. A detailed steady
      state kinetic analysis indicated that each mutant enzyme no longer displayed the
      Ping Pong kinetic behaviour associated with the wild-type enzyme but exhibited
      what was best described as a random bireactant ternary complex mechanism. This
      leads, depending on the chosen substrate concentration, to apparent sigmoidal,
      hyperbolic or complex kinetic behaviour. These experiments, together with others
      reported previously, indicate that simple mutagenic changes in regions distant
      from the active site can lead to dramatic switches in steady-state kinetic
      mechanism.

PMID- 8526867
TI  - Substrate specificity of an aflatoxin-metabolizing aldehyde reductase.
AB  - The enzyme from rat liver that reduces aflatoxin B1-dialdehyde exhibits a unique
      catalytic specificity distinct from that of other aldo-keto reductases. This
      enzyme, designated AFAR, displays high activity towards dicarbonyl-containing
      compounds with ketone groups on adjacent carbon atoms; 9,10-phenanthrenequinone,
      acenaphthenequinone and camphorquinone were found to be good substrates. Although
      AFAR can also reduce aromatic and aliphatic aldehydes such as succinic
      semialdehyde, it is inactive with glucose, galactose and xylose. The enzyme also
      exhibits low activity towards alpha,beta-unsaturated carbonyl-containing
      compounds. Determination of the apparent Km reveals that AFAR has highest
      affinity for 9,10-phenanthrenequinone and succinic semialdehyde, and low affinity
      for glyoxal and DL-glyceraldehyde.

PMID- 8526868
TI  - Methodology for assaying iodide conductance in proteoliposomes: specific
      induction by thyroid membrane protein.
AB  - A sensitive assay is developed to assess the existence of an iodide channel in a
      fraction of solubilized membrane proteins. This step is critical when considering
      various procedures for purification of this channel. Sodium cholate is used as a
      detergent as it does not denature the iodide channel. A simple and rapid method
      involving gel-filtration chromatography is used simultaneously to remove the
      detergent and to adjust the buffer composition, before protein insertion into
      liposomes. The presence of an iodide channel is investigated by measuring the
      iodide conductance of these proteoliposomes at 4 degrees C. An outward iodide
      gradient is set up across the proteoliposomal membrane by anion-exchange
      chromatography, allowing uptake of radiolabelled iodide. This uptake is
      conductive as it is abolished by valinomycin in the presence of potassium. It is
      specifically mediated by a thyroid plasma-membrane protein inserted into
      liposomes, as its denaturation before insertion totally abolished uptake. It was
      observed only within a well-defined fraction of thyroid membrane proteins
      collected by size-exclusion chromatography (molecular mass between 100 and 200
      kDa). Furthermore, it was not observed with other membrane proteins such as ileal
      brush-border-membrane proteins or bacteriorhodopsin. Like many anion channels,
      this conductance was also inhibited by N-phenylanthranilic acid. Optimization of
      the assay is described, validating the measurement of conductive iodide uptake at
      30 s by proteoliposomes reconstituted in a ratio of 10 micrograms of protein to
      90 micrograms of lipid, with an outward iodide gradient (KI 15 mM inside and 1
      microM outside). This assay provides a test of the biological activity of the
      iodide channel at each step of the purification; it can be applied to any anionic
      channel.

PMID- 8526869
TI  - Antisense oligodeoxynucleotide inhibition of delta protein kinase C expression
      accelerates induced differentiation of murine erythroleukaemia cells.
AB  - The potential regulatory role of delta protein kinase C (delta PKC) in murine
      erythroleukaemia cell differentiation was studied by using antisense
      oligodeoxynucleotides targeting the translation initiation region of mouse delta
      PKC mRNA. Cell treatment with antisense oligonucleotides, at a concentration of
      20 microM, followed by hexamethylenebisacetamide induction, produced a specific 2
      fold increase in the differentiation rate of both slowly and rapidly
      differentiating murine erythroleukaemia cell clones. Cell permeabilization by a
      cationic lipid resulted in a decrease of one order of magnitude in the amounts of
      antisense oligonucleotides necessary to elicit the maximal response, and
      accelerated the kinetics of the stimulatory effect. These changes in murine
      erythroleukaemia cell differentiation rates, observed in both cell clones, were
      associated with 60% and 50% decreases, respectively, in delta PKC immunoreactive
      protein in slowly and rapidly differentiating cells. The present results indicate
      strongly that basal levels of delta PKC in murine erythroleukaemia cells are
      essential in regulating the initial differentiation rate of these cells in
      response to chemical induction, and provide further evidence that this PKC
      isoform plays a fundamental role in maintaining the undifferentiated phenotype of
      murine erythroleukaemia cells.

PMID- 8526870
TI  - Decrease in free-radical production with age in rat peritoneal macrophages.
AB  - The respiratory-burst reaction has been studied in rat peritoneal macrophages of
      different ages (3, 12 and 24 months) using phorbol 12-myristate 13-acetate (PMA)
      to stimulate NADPH oxidase. Production of O2-. and H2O2 decreased with age (about
      50 and 75% respectively); however, no difference in NADPH oxidase activity was
      found. NO. production was also reduced with age (40%). Furthermore, a progressive
      and significant decrease in the pentose phosphate flux was detected as a function
      of age in control and PMA-stimulated macrophages. The NADPH/NADP+ ratio decreased
      with age in control and PMA-stimulated macrophages. Glucose uptake was lower in
      middle-aged (12 months) and old (24 months) animals but no differences were found
      between these groups.

PMID- 8526871
TI  - Enzymes of ecdysteroid transformation and inactivation in the midgut of the
      cotton leafworm, Spodoptera littoralis: properties and developmental profiles.
AB  - In the midgut cytosol of Lepidoptera, ecdysteroids undergo inactivation by
      transformation via the 3-dehydro derivative to the corresponding 3-epiecdysteroid
      (3 alpha-hydroxy) and by phosphate conjugation. The oxygen-dependent oxidase
      catalyses formation of 3-dehydroecdysteroid, which can be reduced either
      irreversibly by 3-dehydroecdysone 3 alpha-reductase to 3-epiecdysteroid, or by 3
      dehydroecdysone 3 beta-reductase back to the initial ecdysteroid. Furthermore,
      these ecdysteroids undergo further inactivation by phosphorylation. These
      ecdysteroid transformations have been investigated in last instar larvae of the
      cotton leafworm, Spodoptera littoralis. The products of the phosphorylation have
      been characterized as predominantly ecdysteroid 2-phosphate accompanied by
      smaller amounts of the corresponding 22-phosphate. The phosphotransferases
      require Mg2+ and ATP. Whereas the 3-dehydroecdysone 3 alpha-reductase has a clear
      preference for NADPH rather than NADH, the corresponding 3 beta-reductase
      markedly favours NADH. The physiological significance of the latter enzyme is
      unclear. The profiles of the various enzymic activities in dialysed midgut
      cytosol supplemented with appropriate cofactors were determined throughout the
      last larval instar. All activities were detectable throughout the instar, but the
      respective enzymes exhibited maxima at different times. Ecdysone oxidase showed a
      peak early in the instar, with 3-dehydroecdysone 3 alpha-reductase increasing to
      a peak as the former activity declined. The 3-dehydroecdysone 3 beta-reductase
      exhibited peak activity late in the instar, a profile similar to that observed
      for the corresponding haemolymph enzyme involved in reduction of the 3
      dehydroecdysone product of the prothoracic glands to ecdysone. Thus, the
      significance of the midgut 3 beta-reductase may be related to production of
      active hormone. Both ecydsteroid 22- and 2-phosphotransferases showed high
      activities early in the instar and then declined. The physiological significance
      of the profiles for the ecdysone oxidase, the 3-dehydroecdysone 3 alpha-reductase
      and phosphotransferases is unclear.

PMID- 8526872
TI  - Purification, characterization and specificity of chondroitin lyases and
      glycuronidase from Flavobacterium heparinum.
AB  - The chondroitin lyases from Flavobacterium heparinum (Cytophaga heparinia) have
      been widely used in depolymerization of glycosaminoglycan and proteoglycan
      chondroitin sulphates. Oligosaccharide products derived from chondroitin sulphate
      can be further degraded by glycuronidases and sulphatases obtained from the same
      organism. There has been no reported purification of these enzymes to homogeneity
      nor is there any information on their physical and kinetic characteristics. The
      absence of pure enzymes has resulted in a lack of understanding of the optimal
      conditions for their catalytic activity and their substrate specificity. This has
      limited the use of these enzymes as reagents for preparation of oligosaccharides
      for structure and activity studies. Reproducible schemes to purify a chondroitin
      AC lyase, a glycuronidase and chondroitin B lyase from Flavobacterium heparinum
      to apparent homogeneity are described. Chondroitin AC lyase (chondroitinase AC,
      EC 4.2.2.5), glycuronidase [chondro-(1-->3)-glycuronidase, no EC number] and
      chondroitin B lyase (chondroitinase B, no EC number) have M(r) values (assessed
      by SDS/PAGE) of 74,000, 41,800 and 55,200 respectively, and isoelectric points
      (determined by isoelectric focusing) of 8.85, 9.28 and 9.05 respectively.
      Chondroitin lyase AC and B contain pyroglutamic acid at their N-termini
      precluding their analysis by Edman degradation. Deblocking with pyroglutamate
      aminopeptidase facilitated the determination of their N-terminal sequences. The
      kinetic properties of these enzymes have been determined as well as the optimum
      conditions for their catalytic activity. The specificity of the glycouronidase,
      determined using 17 different disaccharide substrates, shows that it only acts on
      unsulphated or 6-O-sulphated 1-->3 linkages. The chondroitin lyases are both
      endolytic enzymes, and oligosaccharide mapping shows their expected specificity
      towards the chondroitin and dermatan sulphate polymers.

PMID- 8526873
TI  - Differences in the binding of transforming growth factor beta 1 to the acute
      phase reactant and constitutively synthesized alpha-macroglobulins of rat.
AB  - Human alpha 2-macroglobulin (alpha 2M) is a proteinase inhibitor and carrier of
      certain growth factors, including transforming growth factor beta 1 (TGF-beta 1).
      The constitutively synthesized homologue of human alpha 2M in the adult rat is
      alpha 1M. Rat alpha 2M is an acute-phase reactant, expressed at high levels in
      experimental trauma, pregnancy and in certain pathological conditions. The
      physiological role of rat alpha 2M is not known. In this investigation, we
      demonstrated that rat alpha 1M and rat alpha 2M bind TGF-beta 1. The equilibrium
      dissociation constants (KD) for the binding of TGF-beta 1 to the native forms of
      alpha 1M and alpha 2M were 257 and 109 nM respectively. alpha 1M underwent
      conformational change when it reacted with methylamine. The resulting product
      bound TGF-beta 1 with higher affinity (32 nM). Methylamine-treated rat alpha 2M
      did not undergo conformational change and did not bind TGF-beta 1 with increased
      affinity. Previous studies suggest that the native conformation may be the
      principal form responsible for the cytokine-carrier activity of alpha 2M in
      plasma and serum-supplemented cell culture medium. To confirm that native rat
      alpha 2M is a more efficient TGF-beta 1 carrier than native alpha 1M, fetal
      bovine heart endothelial cell (FBHE) proliferation assays were performed. TGF
      beta 1 (5 pM) inhibited FBHE proliferation, and native alpha 2M (0.3 microM)
      counteracted this activity whereas alpha 1M (0.3 microM) had almost no effect.
      Rat alpha 2M underwent conformational change when it reacted with plasmin
      incorporating 1.1 mol of plasmin/mol. alpha 2M-plasmin bound TGF-beta 1; the KD
      (61 nM) was lower (P < 0.01) than that determined for the native alpha 2M-TGF
      beta 1 interaction. These studies demonstrate that both rat alpha-macroglobulins
      are carriers of TGF-beta 1. The native form of rat alpha 2M probably has a
      predominant role, compared with native alpha 1M, as a TGF-beta 1 carrier in the
      plasma during the acute-phase response.

PMID- 8526874
TI  - Calponin induces actin polymerization at low ionic strength and inhibits
      depolymerization of actin filaments.
AB  - Calponin from chicken gizzard induced polymerization of actin in the presence of
      10 mM KCl. Only 2 min after the addition of KCl in the presence of a 0.0625
      0.25:1 molar ratio of calponin to actin, a Poisson-type length distribution (with
      an average length of approx. 0.7 micron) was observed with formed actin
      filaments. This result suggests that calponin-actin complexes served as nuclei
      for rapid elongation. Calponin caused a rapid polymerization of actin even in G
      buffer (2 mM Tris/HCl, pH 8.0) which is usually used for depolymerization of
      actin filaments. Binding of calponin at a level of up to 1.25 mol per mol of
      actin was observed in the actin filaments formed in the presence of calponin at
      very low ionic strengths. When actin filaments were exposed to 3.3 mM KCl, by
      dilution with G-buffer, a rapid depolymerization occurred. Addition of calponin
      greatly retarded the depolymerization process and, in the presence of an
      equimolar ratio of calponin to actin, depolymerization hardly occurred. In the
      presence of calmodulin, this inhibitory effect on depolymerization was reversed
      by Ca2+, releasing calponin from actin filaments.

PMID- 8526875
TI  - Characterization of human DNA ligase I expressed in a baculovirus-insect cell
      system.
AB  - The baculovirus expression system was used to overexpress human DNA ligase I
      (hLig I). Approx. 2 mg of recombinant hLig I was produced per 10(8) Spodoptera
      frugiperda Sf9 insect cells infected with the recombinant baculovirus. The
      optimum time point for the production of biologically active recombinant hLig I
      was 48 h post-infection. Lig I activity was demonstrated by auto-adenylating,
      polynucleotide joining and DNA relaxation assays. The baculovirus system has the
      advantage over previously described methods for producing hLig I of generating
      large amounts of a full-length active protein.

PMID- 8526876
TI  - Kinetic characteristics of Escherichia coli RNase H1: cleavage of various
      antisense oligonucleotide-RNA duplexes.
AB  - 1. The effects of variations in substrates on the kinetic properties of
      Escherichia coli RNase H were studied using antisense oligonucleotides of various
      types hybridized to complementary oligoribonucleotides. The enzyme displayed
      minimal sequence preference, initiated cleavage through an endonucleolytic
      mechanism near the 3' terminus of the RNA in a DNA-RNA chimera and then was
      processively exonucleolytic. Phosphorothioate oligodeoxynucleotides hybridized to
      RNA supported cleavage more effectively than phosphodiester
      oligodeoxynucleotides. Oligonucleotides comprised of 2'-methoxy-, 2'-fluoro- or
      2'-propoxy-nucleosides did not support RNase H1 activity. 2. The Km and Vmax. of
      cleavage of RNA duplexes with full phosphorothioate oligodeoxynucleotides were
      compared with methoxy-deoxy 'gapmers', i.e.; oligonucleotides with 2'-methoxy
      wings surrounding a deoxynucleotide centre. Such structural modifications
      resulted in substantial increases in affinity, but significant reductions in
      cleavage efficiency. The initial rates of cleavage increased as the
      deoxynucleotide gap size was increased. Multiple deoxynucleotide gaps increased
      the Vmax. but had little effect on Km. 3. The effects of several base
      modifications on the site of initial cleavage, processivity and initial rate of
      cleavage were also studied.

PMID- 8526877
TI  - Tissue-specific expression of two aldose reductase-like genes in mice: abundant
      expression of mouse vas deferens protein and fibroblast growth factor-regulated
      protein in the adrenal gland.
AB  - Aldose reductase (AR), the first enzyme in the polyol pathway, has been
      implicated in the pathogenesis of diabetic complications, although its
      physiological role is unclear. In mice, besides AR, two AR-like proteins, mouse
      vas deferens protein (MVDP) and fibroblast growth factor-regulated protein (FR
      1), have been reported recently. Tissue-specific expression of these two genes
      was examined using the RNase protection assay method. Contrary to previous
      reports, MVDP was detected in a variety of tissues besides the vas deferens. High
      levels of MVDP mRNA were found in the adrenal glands, and low levels of
      expression were detected in eye, intestine, seminal vesicle, kidney, liver,
      testis and lung. The major gene expression pattern for FR-1 was slightly
      different from that of MVDP, with the highest levels of mRNA detected in testis,
      heart, adrenal gland, and ovary; less was found in the lung and it was barely
      detectable in eye, intestine, liver and seminal vesicle tissue. Mouse embryos, as
      early as 10.5 days post coitum, expressed both genes, although the levels of
      expression were different. Human AR mRNA was found in human vas deferens,
      although not at the high level found in mice. The localization of both MVDP and
      FR-1 transcripts in the adrenal cortex by in situ hybridization led to the
      speculation that these two AR-like proteins could be related to hormone
      production.

PMID- 8526878
TI  - Location of smooth-muscle myosin and tropomyosin binding sites in the C-terminal
      288 residues of human caldesmon.
AB  - We have produced nine recombinant fragments, H1 to H9, from a human cDNA that
      codes for the C-terminal 288 residues of caldesmon. The fragment H1, encompassing
      the 288 residues, is equivalent to domains 3 and 4 of caldesmon (amino acids 506
      793 in human, 476-737 in the chicken gizzard sequence). It has been shown [Huber,
      Redwood, Avent, Tanner and Marston (1993) J. Muscle Res. Cell Motil. 14, 385-391]
      to bind to actin, Ca(2+)-calmodulin, tropomyosin and myosin. The fragments, H2 to
      H9, differ in length between 60 and 176 residues and cover the whole of domains 3
      and 4 with many of the fragments overlapping. We have characterized the myosin
      and tropomyosin binding of these fragments. The binding of both tropomyosin and
      myosin is highly dependent on salt concentration, indicating the ionic nature of
      these interactions. The location of the myosin binding is an extended region
      encompassing the junction of domains 3/4 and domain 4a (residues 622-714, human;
      566-657, chicken gizzard). Tropomyosin binds in a smaller region within domain 4a
      of caldesmon (residues 663-714, human; 606-657 chicken gizzard). We confirmed
      predictions based on sequence similarities of a tropomyosin binding site in
      domain 3 of caldesmon; however, this site bound to skeletal-muscle tropomyosin
      and had little affinity for the smooth-muscle tropomyosin isoform. None of the
      protein fragments H2-H9 retained the affinity of the parent fragment H1 for
      either myosin or tropomyosin. This indicates the need for several interaction
      sites scattered over an extended region to attain higher affinity. The regions
      interacting with caldesmon in both tropomyosin and myosin are coiled-coil
      structures. This is probably the reason for their shared interaction sites on
      caldesmon and their similar natures of binding.

PMID- 8526879
TI  - Translational regulation during activation of porcine peripheral blood
      lymphocytes: association and phosphorylation of the alpha and gamma subunits of
      the initiation factor complex eIF-4F.
AB  - Mature peripheral blood lymphocytes exist in a resting state both in vivo and
      when maintained in culture, exhibiting low translation rates consistent with
      their non-proliferative state. Previously we have shown that activation of these
      quiescent cells with either phorbol ester or concanavalin A leads to a rapid
      increase in the rate of protein synthesis and phosphate-labelling of initiation
      factor eIF-4 alpha [Morley, Rau, Kay and Pain (1993) Eur. J. Biochem. 218, 39
      48]. We now show that neither the early enhanced translation rate nor the early
      increased phosphate-labelling of eIF-4 alpha requires the activity of the 70 kDa
      form of ribosomal protein S6 kinase. In addition, we demonstrate that eIF-4 gamma
      is phosphorylated in response to cell activation, an event which is correlated
      with phosphorylation of eIF-4 alpha and enhanced eIF-4F complex formation. In
      these studies, isoelectric focusing and immunoblot analysis of eIF-4 alpha
      indicate that phosphate-labelling of eIF-4 alpha following cell activation
      reflects a modest increase in steady-state phosphorylation, mediated by the
      enhanced activity of eIF-4 alpha kinase(s) and inhibition of eIF-4 alpha
      phosphatase activity. In the resting cell, eIF-4 alpha is associated with heat-
      and acid-stable insulin-responsive protein (PHAS-I; 4E-BP1); following acute
      stimulation with phorbol ester, there is a 40% decrease in the amount of PHAS-I
      associated with eIF-4 alpha. Incubation of anti-PHAS-I immunoprecipitates with
      extracts containing activated or immunprecipitated mitogen-activated protein
      kinase resulted in a small increase in phosphorylation of recovered PHAS-I and a
      modest release of eIF-4 alpha from the PHAS-I-eIF-4 alpha complex. These data
      suggest a possible role for PHAS-I in the regulation of eIF-4F complex formation
      and the rate of translation in primary cells.

PMID- 8526880
TI  - Activation of mitogen-activated protein kinases by stimulation of the central
      cannabinoid receptor CB1.
AB  - The G-protein-coupled central cannabinoid receptor (CB1) has been shown to be
      functionally associated with several biological responses including inhibition of
      adenylate cyclase, modulation of ion channels and induction of the immediate
      early gene Krox-24. Using stably transfected Chinese Hamster Ovary cells
      expressing human CB1 we show here that cannabinoid treatment induces both
      phosphorylation and activation of mitogen-activated protein (MAP) kinases, and
      that these effects are inhibited by SR 141716A, a selective CB1 antagonist. The
      two p42 and p44 kDa MAP kinases are activated in a time- and dose-dependent
      manner. The rank order of potency for the activation of MAP kinases with various
      cannabinoid agonists is CP-55940 > delta 9-tetrahydrocannabinol > WIN 55212.2, in
      agreement with the pharmacological profile of CB1. The activation of MAP kinases
      is blocked by pertussis toxin but not by treatment with hydrolysis-resistant
      cyclic AMP analogues. This suggests that the signal transduction pathway between
      CB1 and MAP kinases involves a pertussis-toxin-sensitive GTP-binding protein and
      is independent of cyclic AMP metabolism. This coupling of CB1 subtype and
      mitogenic signal pathway, also observed in the human astrocytoma cell line U373
      MG, may explain the mechanism of action underlying cannabinoid-induced Krox-24
      induction.

PMID- 8526881
TI  - A modified spectroscopic method for the determination of the transbilayer
      distribution of phosphatidylethanolamine in soya-bean asolectin small unilamellar
      vesicles.
AB  - A spectroscopic kinetic approach for determining the relative concentrations of
      phosphatidylethanolamine (PE) exposed on the external and internal layers of
      small unilamellar vesicles (SUVs) used as a model system and prepared by
      sonication of purified soya-bean asolectin is proposed, based on the use of 2,4,6
      trinitrobenzenesulphonic acid (TNBS) and N-succinimidyl 3-(2
      pyridyldithio)propionate (SPDP). The known reactions between PE and TNBS and/or
      SDPD were used, separately or in combination, to derivatize PE in preformed
      vesicles. We have observed that mixing SUVs with excess TNBS results in a
      biphasic time course. Kinetic analysis of the data supports the conclusion that
      external PE is rapidly derivatized (fast phase) with a half-time of 2 min. In the
      next (slow) phase (half-time 70 min), TNBS permeates the vesicle membrane and
      also reacts with PE molecules facing the internal liposomal compartment. Under
      the experimental conditions chosen, SPDP reacted with only the external PE
      molecules. The reaction of SUVs first derivatized with SPDP and then with TNBS
      further demonstrates that the two phases, observed with TNBS, are due to
      modification of external and internal PE. Approx. 30% of PE was found to be
      facing the external bulk phase, thus confirming the asymmetric distribution of
      the molecules in SUVs. The maximum number of thiol arms covalently linked by
      means of SPDP modification of PE on the surface of a single liposome was
      estimated at about 10(2).

PMID- 8526882
TI  - E1A--oncogene or tumor suppressor?

PMID- 8526883
TI  - Chromosomes take an active role in spindle assembly.
AB  - The assembly of a bipolar spindle is essential for the accurate segregation of
      replicated chromosomes during cell division. Do chromosomes rely solely on other
      cellular components to regulate the assembly of the bipolar spindle or are they
      masters of their own fate? In the Zhang and Nicklas(1) study reviewed here,
      micromanipulation techniques and video microscopy were used to demonstrate the
      different roles that chromosome arms, kinetochores and centrosomes play in
      bipolar spindle assembly.

PMID- 8526884
TI  - Protein synthesis in eukaryotic organisms: new insights into the function of
      translation initiation factor eIF-3.
AB  - The pathway for initiation of protein synthesis in eukaryotic cells has been
      defined and refined over the last 25 years using purified components and in vitro
      reconstituted systems. More recently, powerful genetic analysis in yeast has
      proved useful in unraveling aspects of translation inherently more difficult to
      address by strictly biochemical approaches. One area in particular is the
      functional analysis of multi-subunit protein factors, termed eukaryotic
      initiation factors (eIFs), that play an essential role in translation initiation.
      eIF-3, the most structurally complex of the eIFs, has until recently eluded this
      approach. The identification of the yeast GCD10 gene as the structural gene for
      the zeta subunit of yeast eIF-3(1) and the analysis of mutant phenotypes has
      opened the door to the genetic dissection of the eIF-3 protein complex.

PMID- 8526885
TI  - The anterior-posterior and dorsal-ventral axes have a common origin in Drosophila
      melanogaster.
AB  - The mechanisms governing anterior-posterior and dorsal-ventral polarity in
      Drosophila melanogaster had previously been considered as independent processes.
      However, two papers(1,2) now reveal that both axes are initiated during oogenesis
      by the same pathway, and also clearly demonstrate that one is dependent on the
      other.

PMID- 8526886
TI  - Life and death by p53.
AB  - p53 is a multifunctional protein which plays a role in modulating gene
      transcription, policing cell cycle checkpoints, activating apoptosis, controlling
      DNA replication and repair, maintaining genomic stability and responding to
      genetic insults. Mutation of the p53 gene confers the single greatest known
      selective advantage favoring cancer formation. Point mutations result not only in
      the loss of tumor suppressor functions, but also in the gain of tumor promotion
      functions. These dual circumstances may be unique to p53 and, in part, could
      explain the relatively powerful force behind this selection pressure. General
      mechanisms of gain of function by mutated p53 may include alteration in
      transcriptional modulation and newly acquired targets for transcriptional
      regulation and protein binding. Despite the direct significance of p53 mutations,
      loss of the remaining wild-type allele is usually required for the formation of
      tumors in the natural setting. Novel applications of the basic scientific
      knowledge of p53 could lead to an improvement in cancer treatment, hopefully in
      the not so distant future.

PMID- 8526887
TI  - Transparent things: cell fates and cell movements during early embryogenesis of
      zebrafish.
AB  - Development of an animal embryo involves the coordination of cell divisions, a
      variety of inductive interactions and extensive cellular rearrangements. One of
      the biggest challenges in developmental biology is to explain the relationships
      between these processes and the mechanisms that regulate them. Teleost embryos
      provide an ideal subject for the study of these issues. Their optical lucidity
      combined with modern techniques for the marking and observation of individual
      living cells allow high resolution investigations of specific morphogenetic
      movements and the construction of detailed fate maps. In this review we describe
      the patterns of cell divisions, cellular movements and other morphogenetic events
      during zebrafish early development and discuss how these events relate to the
      formation of restricted lineages.

PMID- 8526888
TI  - A fragile gene.
AB  - Fragile X syndrome is the most common cause of inherited mental retardation in
      humans. The fragile X gene (FMR1) has been cloned and the mutation causing the
      disease is known. The molecular basis of the disease is an expansion of a
      trinucleotide repeat sequence (CGG) present in the first exon within the 5'
      untranslated region of the FMR1 gene. Affected individuals have repeat CGG
      sequences of above 200. As a result the gene is not producing protein. It has
      been shown that the FMR1 protein has RNA binding activity, but the function of
      this RNA binding activity is not known. The timing and mechanism of repeat
      amplification are not yet understood. An animal model for fragile X syndrome has
      been generated, which can be used to study the clinical and biochemical
      abnormalities caused by absence of FMR1 protein product.

PMID- 8526889
TI  - Menage a trois: double strand break repair, V(D)J recombination and DNA-PK.
AB  - All organisms possess mechanisms to repair double strand breaks (dsbs) generated
      in their DNA by damaging agents. Site-specific dsbs are also introduced during
      V(D)J recombination. Four complementation groups of radiosensitive rodent mutants
      are defective in the repair of dsbs, and are unable to carry out V(D)J
      recombination effectively. The immune defect in Severe Combined Immunodeficient
      (scid) mice also results from an inability to undergo effective V(D)J
      recombination, and scid cell lines display a repair defect and belong to one of
      these complementation groups. These findings indicate a mechanistic overlap
      between the processes of DNA repair and V(D)J recombination. Recently, two of the
      genes defined by these complementation groups have been identified and shown to
      encode components of DNA-dependent protein kinase (DNA-PK). We review here the
      three fields which have become linked by these findings, and discuss the
      involvement of DNA-PK in dsb rejoining and in V(D)J recombination.

PMID- 8526890
TI  - Stress signaling in yeast.
AB  - In the yeast Saccharomyces cerevisiae three positive transcriptional control
      elements are activated by stress conditions: heat shock elements (HSEs), stress
      response elements (STREs) and AP-1 responsive elements (AREs). HSEs bind heat
      shock transcription factor (HSF), which is activated by stress conditions causing
      accumulation of abnormal proteins. STREs mediate transcriptional activation by
      multiple stress conditions. They are controlled by high osmolarity via the HOG
      signal pathway, which comprises a MAP kinase module and a two-component system
      homologous to prokaryotic signal transducers. AREs bind the transcription factor
      Yap1p. The three types of control elements seem to have overlapping, but distinct
      functions. Some stress proteins encoded by HSE-regulated genes are necessary for
      growth of yeast under moderate stress, products of STRE-activated genes appear to
      be important for survival under severe stress and ARE-controlled genes may mainly
      function during oxidative stress and in the response to toxic conditions, such as
      caused by heavy metal ions.

PMID- 8526891
TI  - Towards unraveling the complexity of T cell signal transduction.
AB  - Activation of resting T lymphocytes through the T cell antigen receptor complex
      is initiated by critical phosphorylation and dephosphorylation events that
      regulate the function and interaction of a number of signaling molecules. Key
      elements in these reactions are members of the Src, Syk and Csk families of
      protein tyrosine kinases (PTKs) and the phosphotyrosine phosphatases (PTPases)
      that regulate and/or counteract them, such as CD45. The PTKs can
      autophosphorylate and phosphorylate each other at multiple sites and, as the
      result of these interactions, they are induced to phosphorylate other cellular
      proteins. These phosphorylation events lead to modulation of enzymatic activities
      and/or serve as binding sites for other signaling molecules having
      phosphotyrosine-binding Src homology 2 (SH2) domains. As a result, these proteins
      translocate to the receptor complexes and are juxtaposed to the kinases that
      phosphorylate them. Some of the SH2-domain-containing polypeptides lack enzymatic
      activities and, instead, serve as adapter molecules that couple the signal to
      downstream effectors, such as regulators of the Ras proteins, and further into
      serine/threonine-specific protein kinase cascades. Through largely unknown steps
      these reactions lead to the transcription of previously silent genes, activation
      of lymphocyte effector functions, progression through the cell cycle and cell
      proliferation.

PMID- 8526892
TI  - The macrophage.
AB  - The macrophage plays an important role in host development and physiology, and in
      pathogenesis of many infectious, immunologic and degenerative disease processes.
      It displays marked heterogeneity of phenotype in different tissues, reflecting
      local interactions with other cell types, and contributes to host homeostasis
      through a varied repertoire of plasma membrane and secretory molecules. Upon
      isolation from the body it continues to express special, as well as general,
      features of cellular organisation and function, which make it a delight to study
      in cell culture.

PMID- 8526893
TI  - Does replication-induced transcription regulate synthesis of the myriad low copy
      number proteins of Escherichia coli?
AB  - Over 80% of the genes in the E. coli chromosome express fewer than a hundred
      copies each of their protein products per cell. It is argued here that
      transcription of these genes is neither constitutive nor regulated by protein
      factors, but rather, induced by the act of replication. The utility of such
      replication-induced (RI) transcription to the temporal regulation of synthesis of
      determinate quantities of low copy number (LCN) proteins is described. It is
      suggested that RI transcription may be necessitated, as well as facilitated, by
      the folding of the bacterial chromosome into a compact nucleoid. Mechanistic
      aspects of the induction of transcription by replication are discussed with
      respect to the modulation of transcriptional initiation by negative supercoiling
      effects, promoter methylation status and derepression. It is shown that RI
      transcription offers plausible explanations for the constancy of the C period of
      the E. coli cell cycle and the remarkable conservation of gene order in the
      chromosomes of enteric bacteria. Some experimental tests of the hypothesis are
      proposed.

PMID- 8526894
TI  - Development, databases and the Internet.
AB  - There is now a rapidly expanding population of interlinked developmental biology
      databases on the World Wide Web that can be readily accessed from a desk-top PC
      using programs such as Netscape or Mosaic. These databases cover popular
      organisms (Arabidopsis, Caenorhabditis, Drosophila, zebrafish, mouse, etc.) and
      include gene and protein sequences, lists of mutants, information on resources
      and techniques, and teaching aids. More complex are databases relating domains of
      gene expression to embryonic anatomy and these range from existing text-based
      systems for specific organs such as kidney, to a massive project under
      development, that will cover gene expression during the whole of mouse
      embryogenesis. In this brief article, we review selected examples of databases
      currently available, look forward to what will be available soon, and explain how
      to gain access to the World Wide Web.

PMID- 8526895
TI  - Characterization and cloning of the cathepsin L proteinases of Schistosoma
      japonicum.
AB  - Adult Schistosoma japonicum parasites synthesize and secrete both cathepsin L and
      cathepsin B cysteine proteinases. The specific activities of cathepsin L were
      many-fold higher than that of cathepsin B. The cDNAs encoding two distinct
      cathepsin L proteinases, here termed cathepsin L1 and L2, were isolated. The
      deduced amino acid sequences of the mature cathepsin L1 and L2 were approximately
      41% identical, and moreover, S. japonicum cathepsin L2 showed more similarity
      with human cathepsin L than with schistosome cathepsin L1. Schistosome cathepsin
      L proteinases may be involved in the digestion of hemoglobin obtained from host
      erythrocytes. However, since we detected their presence in schistosome eggs, the
      release of these enzymes by eggs trapped in the liver and other organs may be
      associated with the granulomatous responses which characterize the pathology of
      human schistosomiasis.

PMID- 8526896
TI  - Immunological and partial sequence identity of mouse BM180 with wheat alpha
      gliadin.
AB  - BM180, a novel 180-kDa basement membrane protein enriched in guanidine-HCl
      extracts of lacrimal and parotid exocrine secretory glands, was immunopurified
      using the secretion inhibitory monoclonal antibody 3E12. The N-terminal amino
      acid sequence was found to be VRVPVPQLQPQNP. An identical sequence comprises the
      N-terminus of the wheat storage protein alpha-gliadin. The presence of a gliadin
      like protein in basement membranes was confirmed using a monoclonal and several
      polyclonal anti-gliadin antibodies, the former of which detected a 180-kDa
      protein in basement membrane blots. A full-length alpha-gliadin cDNA was found to
      hybridize at high stringency with mouse and human genomic DNA; and in lacrimal
      gland Northern blots with a 2.3-kb message. Since BM180 appears to be required
      for stimulus-secretion coupling by lacrimal acinar cells, circulating anti-alpha
      gliadin antibodies associated with Sjogren's syndrome ('Dry Eye') and more
      commonly in Coeliac disease, may be secretion inhibitory.

PMID- 8526897
TI  - Transcriptional expression of mannose receptor gene during differentiation of
      human macrophages.
AB  - Mannose receptor is a differentiation marker of macrophages. Circulating
      monocytes isolated from plasma are devoid of this receptor; upon culture this
      receptor is rapidly expressed. Its expression is modulated by a variety of
      inflammatory and anti-inflammatory agents. In the present study, we investigated
      its transcription level during the differentiation process. Mannose receptor mRNA
      was monitored by quantitative RT-PCR on freshly harvested monocytes and on
      monocytes cultivated up to four days. No transcription was detected in freshly
      harvested cells, the transcription increased during the first 24 h upon adhesion
      and then decreased.

PMID- 8526898
TI  - Regulatory elements in the promoter region of the renal kallikrein gene in
      normotensive vs hypertensive rats.
AB  - The renal kallikrein-kinin system has been implicated in the pathogenesis of
      hypertension. The expression level of the renal kallikrein gene in the kidney is
      significantly lower in spontaneously hypertensive rats (SHR) as compared with
      that of normotensive (SD and WKY) rats. Deletion analysis showed that the
      fragment -356/-188 of the promoter contains a transcriptional silencer(s) and the
      GC rich region located between -77 and -187 is the minimal essential element for
      directing the expression of the CAT reporter gene in mouse L cells. In the kidney
      of normotensive vs hypertensive rats, the nuclear protein factors NF1/CTF and SP1
      bind differently to the renal kallikrein promoter, but similarly in the salivary
      gland. The differential transcriptional regulation of the rat renal kallikrein
      gene in the kidney may be responsible for the genetic difference between
      normotensive and hypertensive rats.

PMID- 8526899
TI  - Zeta PKC in rat preadipocytes: modulation by insulin and serum mitogenic factors
      and possible role in adipogenesis.
AB  - Several PKC isoforms belonging to the three PKCs' subfamilies cPKC alpha and beta
      isoforms, nPKC epsilon isoform and aPKC zeta isoform were detected by Western
      blot in rat preadipocytes. zeta PKC which appears involved in proliferation and
      differentiation of some cellular types was shown to display variations according
      to the preadipocyte anatomical origin and stage of differentiation. A rapid
      increase in zeta PKC in the cytosolic compartment and translocation into the
      nucleus were induced by mitogenic factors in proliferating preadipocytes and by
      insulin in differentiating preadipocytes. These findings suggest that zeta PKC
      could be involved i) in the post-receptor signaling pathway of serum mitogenic
      factors and insulin in preadipocytes, and ii) in the mechanisms underlying the
      variations in the proliferating and differentiating capacities of preadipocytes
      according to their anatomical localization.

PMID- 8526900
TI  - Identification of a rapidly dephosphorylating 95-kDa protein as elongation factor
      2 during 8-Br-cAMP treatment of N1E115 neuroblastoma cells.
AB  - Treatment of 8-Br-cAMP promotes neurite outgrowth and neuronal differentiation in
      N1E115 mouse neuroblastoma cells. Prior or simultaneous treatment of PMA blocks 8
      Br-cAMP-mediated neurite outgrowth. Phosphorylation of cellular proteins during
      these treatments was examined in a permeabilized cell system. While PMA promotes
      phosphorylation of the heat-stable protein kinase C substrates MARCKS and
      neuromodulin, 8-Br-cAMP hastens the dephosphorylation of a protein of M(r)95k
      (p95). Extensively purified, N-terminal sequenced, and judged from its
      phosphorylation properties, p95 was identified as the eukaryotic elongation
      factor-2 (eEF-2), whose dephosphorylation has been reported to be related to an
      increase in protein synthesis. It is likely 8-Br-cAMP stimulates
      dephosphorylation of eEf-2, promotes protein synthesis that eventually leads to
      neuronal differentiation in N1E115 cells.

PMID- 8526901
TI  - Expression of GM-CSF and a functional GM-CSF receptor in the human colon
      carcinoma cell line SW403.
AB  - Only little is known about the expression of a functional granulocyte-macrophage
      colony-stimulating factor receptor (GMR) and its ligands in human colon carcinoma
      cell lines. To obtain more information on this subject, we investigated the human
      colon carcinoma cell line SW403, and we were able to demonstrate the constitutive
      synthesis of a 85-kDa GMR in SW403 cells. After stimulation with 10% fetal calf
      serum, GM-CSF transcripts were expressed as well. The incubation of SW403 cells
      with GM-CSF resulted in an intensive down-regulation of the activity of the
      interferon-gamma-receptor gene, which could be reconstituted by simultaneous
      addition of an anti-GM-CSF antibody. GM-CSF induced an activation of tyrosine
      phosphorylated protein kinases with molecular weights in the range of 30 to 210
      kDa, but it had no effect on the DNA synthesis of SW403 cells.

PMID- 8526902
TI  - Effect of polycation peptides on mitochondrial permeability transition.
AB  - Synthetic polycation peptides obtained with the basic aminoacids lysine, arginine
      and ornithine are able to inhibit the permeability transition induced in
      mitochondria by calcium ions and inorganic phosphate. At least three basic
      aminoacid residues must be present in the peptide in order to elicit the
      inhibitory effect. In the presence of synthetic polycations and similarly to
      spermine, a lack of correlation between inhibition of swelling and glutathione
      release is apparent, since glutathione release occurs before the onset of a large
      amplitude swelling. The same lack of correlation is observed in the presence of
      cyclosporin. From the results obtained with the above reported polycations,
      different in both aminoacid composition and length, it appears that the effect is
      not to be referred to the individual properties of the molecules examined but
      rather to their cationic character; in addition, a critical number of positive
      charges is necessary to elicit the effect.

PMID- 8526903
TI  - The yeast YBR235w gene encodes a homolog of the mammalian electroneutral Na(+)
      (K+)-C1- cotransporter family.
AB  - The YBR235w gene of the yeast Saccharomyces cerevisiae was found during
      sequencing of chromosome II. Here, we show that the 1120 aa protein (Ybr235p)
      encoded by this gene shares strong sequence similarity with the highly related
      electroneutral Na(+)-C1- and Na(+)-K(+)-C1- cotransporters of animal cells. We
      hypothesize that this yeast protein also mediates active uptake of C1- into the
      cell.

PMID- 8526904
TI  - Expression of PTP35, the murine homologue of the protein tyrosine phosphatase
      related sequence IA-2, is regulated during cell growth and stimulated by mitogens
      in 3T3 fibroblasts.
AB  - Protein tyrosine phosphatases (PTPases) have been implicated in the control of
      cell proliferation and differentiation. To isolate new members of this family
      potentially involved in cell growth regulation, we looked for PTPase sequences
      differently expressed in proliferating or quiescent NIH 3T3 fibroblasts. The full
      length cDNA of one of these growth-regulated genes, named PTP35, was isolated
      from a 3T3 library and found to encode the murine IA-2 PTPase-related sequence.
      Endogenous PTP35 mRNA steady-state levels were found to be strictly regulated
      during cell growth in 3T3 fibroblasts, being high in actively cycling cells and
      barely detectable in density-arrested cells. Both PTP35 mRNA and protein levels
      could be induced in quiescent cells by mitogenic stimulation. The growth factor
      specificity and kinetics of this induction were analyzed in detail.

PMID- 8526905
TI  - A novel RNA splicing mutation in Japanese patients with Wilson disease.
AB  - Deletion/insertion mutation of Wilson disease (WD) gene in 16 Japanese patients
      with Wilson disease was studied. A truncated size in a region of exon 4 to 6 was
      found by reverse transcription-polymerase chain reaction (RT-PCR) covering entire
      21 exons except exon 1 for liver cDNA of one patient with a late onset neurologic
      type. Sequence analysis of the cDNA revealed that this truncation was occurred by
      skipping of exon 5, though any mutation in exon 5 of genomic DNA was failed to
      detect. T to G transversion in 5 bp upstream from a junction of intron 4 and exon
      5 was found in genomic DNA of the patient. Further, results obtained by RT-PCR
      and the sequence analysis in intron 4 indicate that the mutation of the patient
      is homozygous. Since same mutation in one allele of another patient out of 15
      patients was found, allele frequency of the splicing mutation in Japanese
      patients is 9.4%. These results suggest that the point mutation in intron 4 of WD
      gene causes the skipping of exon 5 and the splicing mutation affects the
      phenotype of Wilson disease.

PMID- 8526906
TI  - A new selenoprotein found in the glandular epithelial cells of the rat prostate.
AB  - An inverse relationship between the Se status and the incidence of prostate
      cancer suggests a significant role of Se in this organ. After labeling of rats
      with 75Se and sodium dodecyl sulfate-polyacrylamide gel electrophoresis a
      strongly labeled prostatic 15-kDa protein band was found which was equally
      distributed among the different lobes. It was localized in the epithelial cells
      of isolated acini but did not appear in the prostatic secretion. By two
      dimensional electrophoresis the band was resolved into three spots with pI-values
      around 4.5. The most strongly labeled spot stemmed from a cytosolic selenoprotein
      with an apparent native molecular mass of about 300 kDa which contained Se in the
      form of selenocysteine. The fact that with insufficient Se intake the element is
      preferentially incorporated into this compound as compared with glutathione
      peroxidase implies an important function of this newly found prostatic epithelial
      selenoprotein (PES).

PMID- 8526907
TI  - Recognition of human recombinant myelin associated glycoprotein by anti
      carbohydrate antibodies of the L2/HNK-1 family.
AB  - The L2 and HNK-1 monoclonal antibodies recognize carbohydrate determinants
      containing sulfate-3-glucuronate that are prominent on cells of neural crest
      lineages. In humans these epitopes are most abundant on the Myelin Associated
      Glycoprotein and it was assumed that they co-localize on the same molecules.
      Recently, in vitro synthesized carbohydrates have provided a basis for the
      different recognition requirements of these two antibodies. We now provide in
      vivo evidence that a human melanoma cell line can produce glycoproteins such as
      fibronectin, which is recognized by both the L2 and HNK-1 antibodies, and
      simultaneously a transfected Myelin Associated Glycoprotein carrying only L2-type
      carbohydrates. Conceivably, the differential expression of L2- and HNK-1 type
      glycans could have a role in development.

PMID- 8526908
TI  - Short-chain phospholipids enhance amphipathic peptide-mediated gene transfer.
AB  - Addition of short-chain phospholipids to the gramicidin S-DNA-dioleoyl
      phosphatidylethanolamine complex enhanced up to 6-fold beta-galactosidase
      expression in several cell-lines in vitro. Among the compounds tested, the most
      potent in enhancing transfection were the dicapryl- and the dicapryloyl
      phosphatidylcholine. In contrast, no significant enhancement of transfection was
      seen when short-chain phospholipids were mixed with cationic lipids. Short-chain
      phospholipid and gramicidin S may act simultaneously on the cell membrane to
      enhance gene transfer, yet resulting in no toxicity.

PMID- 8526909
TI  - Inhibition of replication initiation by triple helix-forming oligonucleotides.
AB  - Oligonucleotide-directed triple helix formation constitutes a new approach to
      block gene expression via transcription inhibition. In addition triple helices
      might inhibit replication. We have examined the capacity of triple helix-forming
      oligonucleotides to inhibit the initiation of replication on a single-stranded
      DNA template using T7 DNA polymerase (Sequenase). We show that triple helix
      formation at the primer initiation site efficiently inhibits DNA polymerization,
      by preventing binding of the polymerase. The effect is dependent on the distance
      between the 3'-end of the primer and the triple helix boundary. Inhibition
      becomes ineffective when this distance is greater than 3 nucleotides. The
      presence of three base-pairs outside the triple-helical region on the 3'-side of
      the primer is therefore sufficient to allow for initiation of DNA replication.

PMID- 8526910
TI  - Deletion and transfection analysis of the p15/MTS2 gene in malignant gliomas.
AB  - We have investigated the status of the MTS2 gene, encoding the cyclin-dependent
      kinase (CDK) inhibitor p15, in 32 glioblastomas. Semi-quantitative PCR identified
      7 tumors in which the amplified material was 18.6% of controls and 7 in which was
      48.0%, suggesting the occurrence of homozygous and hemizygous deletions,
      respectively. Single strand conformation polymorphism analysis identified one
      polymorphism but no mutations. We also expressed MTS2 and MTS1, encoding the
      contiguous and highly homologous CDK inhibitor p16, in U-87 human glioblastoma
      cells. Both genes, either separately or in combination, inhibit significantly the
      proliferation rate of U-87 cells but such inhibition is progressively lost. As a
      whole, the data assign a tumor suppressor role to p15 and confirm homozygous
      deletions as the favorite mechanism for the inactivation of MTS1 and MTS2 in
      glioblastomas.

PMID- 8526911
TI  - Phospholipase A2-activating peptide-induced contraction of smooth muscle is
      mediated by protein kinase C--MAP kinase cascade.
AB  - The mammalian phospholipase A2-activating protein (PLAP) affects of smooth muscle
      cells isolated from the rabbit rectosigmoid. PLAP (10(6) M)-induced contraction
      peaked at 30 sec and was sustained at 4 min. MAP kinase was activated by PLAP
      (10(-6) M), as measured using myelin basic protein (MBP) as substrate. The
      increase in MAP kinase activity was rapid at 30 sec (159 +/- 2.5%) and remained
      at a sustained level (162 +/- 7.9%) at 4 min. Preincubation of the cells with the
      PLA2 inhibitor ONO-RS-082 (10(-6) M) or with the PKC inhibitor calphostin C (10(
      6) M) resulted in inhibition of contraction, as well as inhibition of the
      associated increase in MAP kinase activation. The data indicates that PLAP
      specific contractile effect on isolated smooth muscle cells is mediated by an
      activation of a PKC-MAP kinase cascade and suggests a putative role for PLA2
      coupled G protein activation of PKC-MAP kinase as an alternate transduction
      pathway in smooth muscle contraction.

PMID- 8526912
TI  - Molecular characterisation of recombinant green fluorescent protein by
      fluorescence correlation microscopy.
AB  - The cDNA for the green fluorescent protein (GFP) of Aequorea victoria has been
      expressed in transformed cells of Saccharomyces cerevisiae and the recombinant
      GFP isolated. Protonation and deprotonation of the cloned and purified GFP
      produced major effects on its spectral absorption characteristics with an
      increase in pH enhancing the fluorescence emission of the GFP more than twofold.
      Finally, molecular characterisation of GFP by fluorescence correlation microscopy
      in a minimal target volume of 1 fL yielded a translational diffusion coefficient
      (DT) of 8.7 x 10(-7) cm2.sec-1, equivalent to a Stokes radius of 2.82nm for a
      monodisperse globular protein of 27kDa.

PMID- 8526913
TI  - Adrenomedullin induces expression of c-fos and AP-1 activity in rat vascular
      smooth muscle cells and cardiomyocytes.
AB  - The recently described hypotensive peptide adrenomedullin has been shown to
      activate various second messenger pathways in cells of the cardiovascular system
      though no genomic actions have yet been described. In cultured rat vascular
      smooth muscle cells, cardiomyocytes, and cardiac fibroblasts, adrenomedullin
      caused a rapid, but transient induction of c-fos mRNA expression in all three
      cell types that varied in magnitude. Adrenomedullin increased AP-1 DNA binding
      activities in vascular smooth muscle cells and cardiomyocytes, but not in cardiac
      fibroblasts. These data suggest that cardiomyocytes and vascular smooth muscle
      cells may be important genomic targets for this novel hormone.

PMID- 8526914
TI  - Preferential interaction of Sec-G with Sec-E stabilizes an unstable Sec-E
      derivative in the Escherichia coli cytoplasmic membrane.
AB  - SecY, SecE and SecG form a membrane part of the protein translocation machinery.
      A SecG-overproducing plasmid was constructed by placing the secG gene under the
      control of the tac promoter. From the extent of SecG overproduction, the number
      of SecG molecules in one normal cell was estimated to be about 1,000, which is
      similar to those of SecY and SecE. Overproduction of SecG stabilized the
      overproduction of SecE-C, an unstable truncated derivative of SecE, as
      effectively as SecY does. SecG overproduction also stabilized the overproduction
      of SecY. However, the SecG-dependent stabilization of SecY was less potent than
      the SecE-dependent stabilization. These results indicate that SecG preferentially
      interacts with SecE, which associates with SecY, the SecG-SecE-SecY complex thus
      being formed in the cytoplasmic membrane.

PMID- 8526915
TI  - Ligand-activated platelet-derived growth factor beta-receptor is degraded through
      proteasome-dependent proteolytic pathway.
AB  - The platelet-derived growth factor beta-receptor undergoes polyubiquitination as
      a consequence of ligand binding. Ubiquitin conjugation to protein is implicated
      in proteasome-dependent proteolytic pathway for short-lived proteins. In the
      present study, we have examined effects of different kinds of cell-penetrating
      proteasome inhibitors, including N-benzyloxycarbonyl-L-isoleucyl-gamma-t-butyl-L
      glutamyl-L-alanyl-L-l eucinal (PSI) and a Streptomyces metabolite lactacystin, on
      ligand-stimulated degradation of the beta-receptor. These proteasome inhibitors
      were found to considerably inhibit the degradation of autophosphorylated and
      polyubiquitinated receptors, suggesting the possible involvement of proteasomes
      in the degradation process of the ligand-activated beta-receptor.

PMID- 8526916
TI  - Thrombopoietin induces tyrosine phosphorylation and activation of mitogen
      activated protein kinases in a human thrombopoietin-dependent cell line.
AB  - Thrombopoietin (TPO) is a cytokine which can support the proliferation and
      differentiation of megakaryocyte progenitor cells, and the maturation of
      megakaryocytes. We show here that mitogen-activated protein (MAP) kinases, Erk1
      and Erk2, are involved in TPO signal transduction in the human TPO-dependent
      megakaryocytic cell line, UT-7/TPO. TPO induced tyrosine phosphorylation of Erk1
      and Erk2 proteins in a dose and time-dependent manner. Moreover, the activation
      of MAP kinases was actually induced by TPO. These results suggest that MAP kinase
      activation is involved in the signalling pathway of TPO, as it is for other
      cytokines, one of which is erythropoietin.

PMID- 8526917
TI  - Molecular cloning and gene mapping of human basic and acidic calponins.
AB  - The nucleotide and deduced amino acid sequences of human basic and acidic
      calponins were determined. The basic calponin cDNA from human aorta (1496 bp)
      contained a single open reading frame (ORF) which encodes 297 amino acids (33,169
      Da). The acidic calponin cDNA from human kidney (1607 bp) contained a single ORF
      which encodes 329 amino acids (36,412 Da). Basic calponin mRNA was expressed in
      only smooth muscle tissues, but acidic calponin mRNA was expressed in non-smooth
      muscle tissues as well as smooth muscle tissues. Fluorescent in situ
      hybridization revealed that basic and acidic calponin genes localize in 19p13.1
      13.2 and 1p21-22 of human chromosomes, respectively.

PMID- 8526918
TI  - Farnesyl-derived inhibitors of ras farnesyl transferase.
AB  - The synthesis and evaluation of farnesyl-derived inhibitors of ras farnesyl
      transferase are presented. Evaluation of inhibitors of farnesyl transferase and
      comparison with the previously described inhibitor was accomplished using
      purified enzyme and Amersham's Farnesyl:Transferase enzyme assay kit. These
      results show an order of magnitude increase in inhibitory activity for beta
      ketophosphonic acid over beta-hydroxyphosphonic acid. Incorporation of fluorines
      in alpha-position, led to an increase in inhibitory activity over the
      nonfluorinated analogues.

PMID- 8526919
TI  - Insulin decreases the glycogen synthase kinase-3 alpha mRNA levels by altering
      its stability in streptozotocin-induced diabetic rat liver.
AB  - The chronic effect of insulin on the expression of the glycogen synthase kinase-3
      alpha gene in streptozotocin-induced diabetic rat liver is examined. The mRNA
      levels of glycogen synthase kinase-3 alpha were increased (143% of normal levels)
      in diabetic livers and these were normalized by insulin supplementation to the
      diabetic animals. Neither diabetes nor insulin supplementation to diabetic rats
      altered the transcription rate of glycogen synthase kinase-3 alpha. However,
      diabetes caused an increase in the half-life of glycogen synthase kinase-3 alpha
      mRNA from 5 h in normal hepatocytes to 8 h in diabetic ones. Insulin
      supplementation to the incubation medium of diabetic hepatocytes decreased the
      half-life of glycogen synthase kinase-3 alpha mRNA to a level comparable with
      normal values. This study suggests that the chronic effect of insulin decreases
      the levels of glycogen synthase kinase-3 alpha mRNA by altering its stability.

PMID- 8526920
TI  - Amino acid sequence analysis of human S100A7 (psoriasin) by tandem mass
      spectrometry.
AB  - The Ca(2+)-binding proteins regulate a number of cellular and extracellular
      activities and deregulations of S100 gene expression are associated with several
      human diseases. For example, S100A7 is upregulated in psoriatic skin, implicating
      a link with psoriasis, a chronic inflammatory dermatosis. We purified human
      S100A7 and determined its protein sequence by tandem mass spectrometry and Edman
      microsequence analysis. Interestingly, a sequence comparison of S100A7 with all
      known human S100 proteins showed that S100A7 is the most divergent of all S100
      proteins.

PMID- 8526921
TI  - Sequential analysis of gene expression after an osteogenic stimulus: c-fos
      expression is induced in osteocytes.
AB  - We have recently developed an experimental model whereby mechanical stimulation
      induces osteogenesis in the caudal vertebrae of rats. We used this model to
      assess expression of genes induced by mechanical loading. Bulk preparations of
      mRNA extracted after loading did not show > 2-fold increases in expression of
      mRNA for matrix proteins or growth factors in Northern blotting analysis. c-jun
      was undectable. However, c-fos showed a 4-fold increase in expression within 60
      mins of loading, before returning to control levels by 4 hrs. This increase was
      associated with intense signals in in situ hybridization, not seen in any
      nonloaded vertebrae, for c-fos over cortical osteocytes: thus osteocytes respond
      to mechanical loading with c-fos expression so strongly as to be visible even in
      the bulk RNA preparations. The results represent persuasive evidence for a role
      for osteocytes, and for c-fos, in the osteogenic response of bone to mechanical
      stimulation.

PMID- 8526922
TI  - Differential expression of transforming growth factor-alpha and epidermal growth
      factor during postnatal development of rat submandibular gland.
AB  - The concentration and the localization of transforming growth factor (TGF)-alpha
      and epidermal growth factor (EGF) in the submandibular glands (SMGs) of male
      Wistar rats of different ages (postnatal 0 to 10 weeks of age) were examined.
      Highest levels of TGF-alpha were seen early, at postnatal day 0; the levels
      dropped thereafter in an age-dependent manner, while EGF was not detectable
      before the third postnatal week. Immunoreactive localization of EGF was
      restricted to the granules of the granular convoluted tubule (GCT) cells in the
      mature SMGs, whereas TGF-alpha was observed throughout postnatal development over
      the entire duct system. TGF-alpha was demonstrated in the cytoplasm at early
      stages when the GCT granules were not observed and was also located on the
      granules at the late stage, as was the case for EGF, indicating that TGF-alpha is
      colocated with EGF in the mature SMG. These results demonstrate the differences
      between the expression of TGF-alpha and that of EGF in the developing rat SMG.

PMID- 8526923
TI  - Advanced glycation end products stimulate plasminogen activator activity via GM
      CSF in RAW 264.7 cells.
AB  - The effects of advanced glycation end products (AGE) on the plasminogen activator
      (PA) activity were investigated with murine macrophage cell line RAW 264.7 cells.
      AGE-bovine serum albumin (BSA) showed a dose-dependent induction for the
      urokinase-type PA (uPA) activity. The uPA induction by AGE-BSA was effectively
      suppressed by the antibody against granulocyte-macrophage colony-stimulating
      factor (GM-CSF). The uPA activity of these cells was also induced by ligands for
      the macrophage scavenger receptor (MSR). These data provide evidence that AGE-BSA
      stimulates the uPA activity via GM-CSF through MSR in RAW cells. These findings,
      taken together with a recent demonstration of endocytic uptake of AGE-proteins by
      MSR in vitro and the presence of AGE-proteins in atherosclerotic lesions,
      strongly suggest that the uPA induction by AGE-proteins via MSR plays an
      important role in human atherogenesis.

PMID- 8526924
TI  - 22-kDa and 20-kDa hGH isoforms show differential effects when assayed in 3T3
      F442A and 3T3-F442A/C4 adipocytes.
AB  - To known whether 22.0-kDa human growth hormone (hGH22K) and the 20.0-kDa isoform
      (hGH20K) show different activities, we used 3T3-F442A and 3T3-F442A/C4 cells to
      evaluate their adipogenic and metabolic effects. Both isoforms had similar
      adipogenic and insulin-like activities. Lipolytic and diabetogenic effects of
      hGH22K were, respectively, 12.5 and 1.7-fold higher than those found for hGH20K.
      The 3T3-F442A/C4 clone was not responsive to insulin-like and diabetogenic
      effects of hGH. The results suggest that adipogenic and lipolytic effects of hGH
      are mediated by mechanisms different from those involved in insulin-like and
      diabetogenic activities.

PMID- 8526925
TI  - The Ca(2+)-dependent activation by fluoride of human red cell membrane sodium
      permeability: evidence for a chemically activated tetrodotoxin-sensitive Na+
      channel.
AB  - Fluoride (NaF) (5-15 mM) activated the 22Na+ uptake by human red blood cells
      (RBC). The effect was Ca(2+)-dependent. Sr2+, but not Ba2+, Mg2+, Mn2+,
      substituted Ca2+ in supporting the 22Na+ uptake. The NaF-induced 22Na+ uptake was
      sensitive to tetrodotoxin (TTX), pertussis toxin but not to amiloride nor
      valinomycin. The value of the influx was 8.6 +/- 5.0 mmol/l cells. Thus, the TTX
      sensitive Na(+)-transport system is present in the RBC membrane in an inactive
      form which could be activated with NaF by a mechanism involving G-protein(s) but
      not the depolarization.

PMID- 8526926
TI  - Galectin-3 is a nuclear matrix protein which binds RNA.
AB  - The endogenous galectin-3 is a carbohydrate-binding protein of M(r) approximately
      30,000 serving in the cytoplasm and on the cell surface as a receptor for ligands
      containing poly-N-acetyllactosamine sequences. In addition, galectin-3 has been
      demonstrated to be associated in the nucleus with ribonucleoprotein complexes and
      to act as a pre-mRNA splicing factor and to be involved in spliceosome assembly.
      However, little is known about either its nuclear localization or its ligand(s),
      respectively. We demonstrate directly here that galectin-3 is associated with the
      RNA protein skeleton of the nucleus, i.e., the nuclear matrix, and binds with
      single-stranded DNA (ssDNA) and with RNA. The affinity of binding was determined
      to be 2.3 microM. Lactose, which inhibits galectin-3 binding to glycoconjugates,
      failed to inhibit either galectin-3-ssDNA or galectin-3-RNA binding. Galectin-3
      exhibited the highest affinity to poly(A) ribonucleotide homopolymers. The
      results presented here shows that galectin-3 may act as a RNA-binding protein in
      the nuclear matrix in a non-carbohydrate-dependent manner.

PMID- 8526927
TI  - cDNA sequence analysis of the human brain insulin receptor.
AB  - Brain tissue mRNA was amplified using polymerase chain reaction (PCR) with eight
      overlapping sets of primers that span the cDNA coding sequence for the human
      placental insulin receptor. Only the A isoform (lacking exon 11) of the receptor
      was detected. No difference was found in the predicted amino acid sequence of
      brain derived insulin receptor cDNA compared with the receptor from human
      placenta. A silent polymorphism was detected at nucleotide position 1698 (amino
      acid 523), confirming that mRNA corresponding to both alleles of the human brain
      receptor was sequenced. Our findings indicate that the unique glycosylation
      properties of brain insulin receptors do not stem from differences in primary
      structure, but rather are due to tissue-specific differences in post
      translational processing.

PMID- 8526928
TI  - Cell cycle phase-dependent changes of localization and oligomerization states of
      nucleophosmin / B23.
AB  - Nucleophosmin / B23, an abundant nucleolar phosphoprotein, accumulates in the
      nucleoplasm of cells during the stationary phase of growth or after exposure to
      selected cytotoxic drugs [Chan, P.K. (1992) Exp. Cell Res. 203, 174-181].
      Monomeric and hexameric forms of nucleophosmin / B23 are present in cells [Yung,
      B.Y.M. and Chan, P.K. (1987) Biochim. Biophys. Acta. 925, 74-82]. Using indirect
      immunofluorescence, here we show that there are changes in nucleophosmin / B23's
      cellular localizations throughout the cell cycle. The alternation of the nuclear
      and nucleolar localizations of nucleophosmin / B23 is most frequently observed in
      cells of G1 and G1/S phases. The incidence of the changes of localizations of
      nucleophosmin / B23 decreases as cells enter into S and G2 phases. In parallel,
      using Western blotting, the reversible change of oligomerization states between
      the hexameric and monomeric forms of nucleophosmin / B23 is also found to occur
      most frequently in cells of G1 and G1/S phases. As cells progressed into S, G2
      and M phases, the frequency of the reversible change of hexameric and monomeric
      forms of nucleophosmin / B23 decreases. These findings suggest that nucleophosmin
      / B23 being possibly involved in rRNA processing and transport, is highly active
      at G1 and G1/S phases as demonstrated by the dynamic, reversible changes of
      localization and oligomerization states of nucleophosmin / B23.

PMID- 8526929
TI  - Inhibition of angiogenesis by thrombospondin-2.
AB  - To assess the ability of proteins of the thrombospondin family to inhibit
      angiogenesis, recombinant murine thrombospondin-2, bovine thrombospondin-2/CISP
      and thrombospondin-5/COMP were purified and tested for ability to block the
      migration of capillary endothelial cells towards a variety of inducers and to
      inhibit neovascularization induced in the rat cornea. Both preparations of
      thrombospondin-2 were active inhibitors in vitro and in vivo whereas
      thrombospondin-5/COMP was inactive. These results define thrombospondin-2 as a
      newly identified naturally occurring inhibitor of angiogenesis and suggest that
      the properdin-like type 1 modules that it shares with antiangiogenic
      thrombospondin-1 and are missing in thrombospondin-5/COMP could contribute to
      this activity.

PMID- 8526930
TI  - The region 3' to the major transcriptional start site of the MDR1 downstream
      promoter mediates activation by a subset of mutant P53 proteins.
AB  - We have examined the response of the human multidrug resistance gene-1 (MDR1)
      downstream promoter to various mutants of human p53 in a reporter assay system.
      Our findings indicate that mutant 175H inhibits reporter activity driven by the
      MDR1 downstream promoter (base pairs -189 to +133 relative to the major
      transcriptional initiation site) in a dose-dependent manner in cotransfection
      assays in the BHK and the Saos-2 cell lines. A 123 base-pair segment of DNA (-119
      to +4 relative to the major transcriptional initiation site) and a 193 base-pair
      segment (-189 to +4) have been isolated from the MDR1 downstream promoter which,
      like the full promoter, are negatively controlled by mutant 175H. However, a 135
      base-pair segment (-2 to +133) of the promoter is activated by mutant 175H as
      well as mutant 248Q, but not by mutants 213Q and 234H. Thus some mutants of p53
      are able to activate transcription from the 3' region of the MDR1 downstream
      promoter, an activity that characterizes these p53 mutants as "gain of function"
      mutants.

PMID- 8526931
TI  - The number of nucleotide binding sites in cytochrome C oxidase.
AB  - The binding of 2'(3')-O-(2,4,6-trinitrophenyl)-adenosine-5'-triphosphate (TNP
      ATP), [35S]ATP alpha S and 8-azido-[gamma-32P]ATP to isolated cytochrome c
      oxidase of bovine heart and liver and to the two-subunit enzyme of Paracoccus
      dentrificans was studied by measuring the fluorescence change or bound
      radioactivity, respectively. With TNP-ATP three binding sites were determined at
      cytochrome c oxidase from bovine heart and liver, both with two dissociation
      constants Kd of about 0.2 and 0.9 microM. Trypsin treatment of the enzyme from
      bovine heart, resulted in one binding site with a Kd of 0.3 microM. The two
      subunit enzyme of Paracoccus dentrificans had only one binding site with a Kd of
      3.6 microM. The binding of [35S]ATP alpha S to cytochrome c oxidase was studied
      by equilibrium dialysis. With the enzyme of bovine heart seven and the enzyme of
      liver six high-affinity binding sites with apparent Kd's of 7.5 and 12 microM,
      respectively, were obtained. The two-subunit enzyme of Paracoccus denitrificans
      had one binding site with a Kd of 20 microM. The large number of binding sites at
      cytochrome c oxidase from bovine heart, mainly at nuclear coded subunits, was
      verified by photoaffinity labelling with 8-azido-[gamma-32P]ATP.

PMID- 8526932
TI  - The cysteine-rich region of dipeptidyl peptidase IV (CD 26) is the collagen
      binding site.
AB  - A remarkable property of the integral glycoprotein dipeptidyl peptidase IV (DPP
      IV, CD 26) is its affinity to proteins of the extracellular matrix (ECM). By in
      vitro binding assays we have shown that DPP IV binds to collagens; preferentially
      to the collagens I and III, which are both characterized by the formation of
      large triplehelical domains. No binding of DPP IV to laminin or fibronectin could
      be observed. Within collagen I, the alpha 1(I) chain was found to be the most
      prominent binding ligand of DPP IV. A monoclonal anti DPP IV antibody (13.4)
      specifically inhibited the interaction of DPP IV with collagen I. Peptide mapping
      and N-terminal sequencing revealed that the corresponding epitope of mAb 13.4 is
      located in the cysteine-rich domain of DPP IV. We therefore conclude that the
      putative collagen binding site of DPP IV is different from the region of the
      catalytic site containing the exopeptidase activity, which is located at the C
      terminal portion of the molecule.

PMID- 8526933
TI  - Detection of growth hormone receptor mRNA in an ovine choroid plexus epithelium
      cell line.
AB  - The expression of growth hormone receptor (GHR) mRNA in an ovine choroid plexus
      cell line (SCP) was studied. RNA isolated from SCP cells was subjected to reverse
      transcription followed by PCR using a set of primers, designed on the basis of
      the ovine liver GHR sequence. A specific product with expected size of 1204 bp
      was obtained and the nucleotide sequence was found to be identical to that of
      ovine liver GHR. When the PCR product was used as a probe for Northern blot
      analysis, a transcript of 4.4 kb was detected in mRNA isolated from the SCP
      cells. This is the first report demonstrating the presence of mRNA for GHR in the
      choroid plexus.

PMID- 8526934
TI  - Truncation of the receptor carboxyl terminus impairs membrane signaling but not
      ligand binding of human ETB endothelin receptor.
AB  - Human ETB endothelin receptor (hETBR) is a heptahelical G-protein-coupled
      receptor consisting of 442 amino acids whose carboxyl (C)-intracellular region
      has four and twelve sites for potential palmitoylation and phosphorylation,
      respectively. In order to elucidate the functional roles of these modification
      sites, we constructed a series of C-terminal truncated hETBRs and expressed them
      in Ltk- cells. All the truncated hETBRs showed ligand-binding profiles similar to
      those of the wild-type hETBR. The truncated receptors holding Cys-402 retained
      both normal intracellular calcium ([Ca2+]i) response and its rapid
      desensitization; however, the deleted receptors lacking Cys-402 failed to induce
      the [Ca2+]i response. These results showed that Cys-402 of hETBR is necessary for
      its intracellular calcium signaling and that at least ten of twelve putative
      phosphorylation sites are irresponsible for the agonist-induced desensitization.

PMID- 8526935
TI  - Stimulation of glyceraldehyde-3-phosphate dehydrogenase mRNA levels by endogenous
      nitric oxide in cytokine-activated endothelium.
AB  - Previous studies have shown that endogenous nitric oxide (NO) potentiates
      glycolysis in the cytokine-activated murine microvascular endothelial cells
      (MME). In the present study we investigate the influence of NO on the expression
      of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an enzyme of the glycolytic
      pathway. Activation of MME with TNF-alpha and IFN-gamma resulted in a strong
      elevation of GAPDH mRNA levels. This effect was impaired in the presence of L
      NMMA, the inhibitor of NO synthesis. We discuss the possibility that NO-mediated
      elevation of GAPDH mRNA levels may compensate for NO-mediated inhibition of GAPDH
      enzymatic activity, representing another adaptive mechanism which protects cells
      producing large amounts of NO against its cytotoxic effects.

PMID- 8526936
TI  - cDNA cloning and functional characterization of rat intestinal monocarboxylate
      transporter.
AB  - A cDNA clone which encodes a monocarboxylate transporter (ratMCT1) was isolated
      from a rat small intestinal cDNA library, which was screened by using full-length
      MCT1 cDNA of Chinese hamster ovary cells. The ratMCT1 cDNA was sequenced and
      predicted a protein of 494 amino acids with twelve potential transmembrane
      domains. The amino acid sequence showed 93.1% and 84.6% identity to the hamster
      and human monocarboxylate transporters, respectively. When expressed in Xenopus
      laevis oocytes, the ratMCT1 cRNA caused a significant increase in the uptake of
      radiolabeled lactic acid. Poly(A)+ RNA transcripts hybridizing to the ratMCT1
      cDNA were detected in rat brain, heart, kidney, lung, muscle and brain
      capillaries. These results indicate that MCT1 contributes to pH-dependent and
      carrier-mediated transport of monocarboxylic acids in many tissues, not just in
      the small intestine.

PMID- 8526937
TI  - Association of estrogen receptor dinucleotide repeat polymorphism with
      osteoporosis.
AB  - We investigated the association between dinucleotide (thymine-adenine) repeat
      polymorphism lying upstream of human estrogen receptor (ER) gene and bone mineral
      density (BMD) as well as biochemical markers for bone metabolism in 144 healthy
      postmenopausal Japanese women. The genotype was classified into 'A' through 'R'
      according to the number of the repeats, from 10 to 27. BMD was expressed in Z
      score (a deviation from the weight-adjusted average BMD of each age using the
      standard deviation as a unit). The people having genotype C (12 repeats of
      thymine-adenine) allele (n = 15) had significantly lower Z score of spine BMD
      (mean +/- SD; -1.11 +/- 1.3 vs. -0.06 +/- 1.2; p < 0.01) and of total body BMD (
      0.58 +/- 1.0 vs. 0.31 +/- 0.9; p < 0.01) than those without this genotype (n =
      129). They also had significantly higher levels of serum intact osteocalcin,
      urinary pyridinoline, and urinary deoxypyridinoline. These results suggest that
      genetic variation at the ER locus may be associated with some determinants for
      BMD and bone metabolism in postmenopausal women.

PMID- 8526938
TI  - Requirement of ATP hydrolysis for assembly of ClpA/ClpP complex, the ATP
      dependent protease Ti in Escherichia coli.
AB  - The ATP-dependent protease Ti (Clp) consists of two distinct components, ClpP
      containing the serine active sites for proteolysis and ClpA having two ATP
      binding sites. A ClpA variant (ClpAT) carrying Thr in place of Met169 is highly
      soluble but indistinguishable from the wild-type ClpA in its ability to hydrolyze
      ATP and to support the ClpP-mediated proteolysis. Here we show that ATP
      hydrolysis is essential for assembly of ClpAT/ClpP complex upon analysis of the
      mixture of its components by gel filtration followed by polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate. Either ADP or
      adenosine 5'-(beta,gamma-imido)-triphosphate could not support the complex
      formation. Furthermore, ClpAT/K501T which carries a mutation in the second ATP
      binding site and therefore is unable to cleave ATP could not interact with ClpP.
      On the other hand, ClpAT/K220T carrying a mutation in the first site and ClpP
      could be assembled into a complex at 2 mM ATP but not at 0.5 mM, at which
      concentration the trimeric mutant protein can not form a hexamer. These results
      indicate that assembly of protease Ti requires hydrolysis of ATP by ClpA in
      addition to its binding for hexamer formation.

PMID- 8526939
TI  - Activation of phospholipase A2 by the human endothelin receptor in Chinese
      hamster ovary cells involves Gi protein-mediated calcium influx.
AB  - The signalling pathways used by the human endothelin A receptor to activate
      phospholipase A2 in Chinese hamster ovary cells were investigated. Pertussis
      toxin caused a partial but significant reduction in endothelin-1-induced
      arachidonic acid release although cAMP-dependent kinase inhibitors did not mimic
      its action. Extracellular calcium and its entry into the cell was essential for
      activation of phospholipase A2 as its removal from media or incubation with an
      intracellular calcium chelator-reduced activation. Nifedipine had no effect on
      endothelin-1-induced arachidonic acid release while divalent cations caused a
      significant reduction indicating the possible role of CRAC. Thapsigargin caused
      an increase in arachidonic acid release which was completely inhibited by
      pertussis toxin treatment. This further supports the involvement of CRAC in
      calcium influx and activation of phospholipase A2 by the human endothelin A
      receptor.

PMID- 8526940
TI  - Accumulation of deletions in MtDNA during tissue aging: analysis by long PCR.
AB  - Multiple deletions of mtDNA have not only been implicated in aging, but also in a
      wide variety of pathological conditions. The enzyme system used in long-PCR makes
      it possible to synthesize the entire mitochondrial genome (16.5 kb), exposing the
      multiple deletions in mtDNAs implicated in and, at least partially, responsible
      for these pathologies. But it is not the number or type of anomalous mtDNA that
      is crucial, rather it is their frequency relative to the number of intact copies
      of the mitochondrial genome. Our work exposes the necessity of quantitating the
      number of normal mitochondrial DNAs. The accuracy of the technique and the small
      sample size required permit one to detect multiple deletions, located in a
      specific organ, and simultaneously measure the fraction of intact molecules. This
      fraction can then be correlated with mitochondrial dysfunction to serve both as
      an indicator of tissue aging and a monitor of an impending myopathy.

PMID- 8526941
TI  - A hydrophobic region of ricin A chain which may have a role in membrane
      translocation can function as an efficient noncleaved signal peptide.
AB  - Ricin A chain is a polypeptide of 267 amino acids containing a hydrophobic region
      near its carboxyl-terminus (residues 245-256) which has been implicated in the
      membrane translocation step necessary for this catalytically active toxin to
      reach its intracellular substrate. DNA fusions were constructed that encoded
      hybrid proteins consisting of carboxyl-terminal residues 233-267 or residues 238
      267 of ricin A chain preceding mouse dihydrofolate reductase. When in vitro
      transcripts prepared from these constructs were translated in cell-free systems,
      the ricin A chain-derived sequences functioned as efficient signal peptides which
      directed dihydrofolate reductase into microsomes or into proteoliposomes
      containing microsomal membrane components.

PMID- 8526942
TI  - IL-12 rescues galactosamine-loaded mice from lethal shock triggered by
      staphylococcal enterotoxin.
AB  - Staphylococcal enterotoxin B (SEB) causes lethal shock in D-galactosamine
      sensitized mice. The lethal shock triggered by SEB is mediated by T cells. We
      found that the lethal shock was restricted by MHC class II molecule. In addition,
      consecutive oral exposures to SEB induced tolerance against the shock in the SEB
      sensitive mice. To elucidate the tolerance mechanism, the role of anti
      inflammatory cytokines was examined. RT-PCR analysis revealed that CD4+ T cells
      from the SEB-sensitive mice expressed significant levels of IFN-gamma, IL-2, IL-4
      and IL-10 mRNA, while those from the tolerant mice exhibited significant levels
      of IFN-gamma but not IL-2 or IL-4 mRNA. These results indicate that polarity of T
      helper (Th) cells from Th0 to Th1 was involved in the tolerance to the SEB
      induced lethal shock. Lymphoid tissues of the tolerant mice generated mRNA of IL
      12, a cytokine which favors Th1 response. It was also demonstrated that
      intraperitoneal administration of IL-12 conferred protection against the lethal
      shock in the sensitive mice.

PMID- 8526943
TI  - A lipid droplet-specific capsule is present in rat adrenal cells: evidence from a
      monoclonal antibody.
AB  - We have used a monoclonal antibody, A2, to study the structure and function on
      the lipid droplet capsule in steroidogenic adrenal cells. This antibody reacts
      with a 160-kD protein found in the rat adrenal cortex. Immunofluorescence
      microscopy shows a dominant rim pattern, which surrounds individual lipid
      droplets and is distinct from the filamentous vimentin staining. The boundary of
      lipid droplets in steroidgenic Leydig cells and 3T3 adipocytes is also
      immunostained by this antibody. The strong association of the 160-kD protein with
      the lipid droplet is demonstrated by its resistance to Triton X-100 extraction.
      Stimulation of steroid secretion by adrenocorticotropin results in the detachment
      of this protein from the lipid droplet and its movement to the cytosol. These
      findings suggest that the translocation of this 160-kD protein from lipid droplet
      surface to cytosol on stimulation might be important in facilitating the binding
      of cholesterol ester hydrolase to the surface of lipid droplets, as proposed for
      adipocytes, during lipolytic stimulation.

PMID- 8526944
TI  - A nonsense mutation of the ceruloplasmin gene in hereditary ceruloplasmin
      deficiency with diabetes mellitus.
AB  - A novel mutation of the ceruloplasmin (Cp) gene was found in a patient with
      hereditary ceruloplasmin deficiency (HCD) with diabetes mellitus (DM). The
      patient had been treated for DM for about 13 years, and then his illness was
      diagnosed as HCD. One year later, he was found dead in his home. A decrease in
      insulin-immunostained cells was observed in the islets of the patient's pancreas
      tissue, which accounted for his DM. The polymerase chain reaction (PCR)-direct
      sequencing analysis of the Cp gene of his daughter revealed a novel point
      mutation, G to A, at nucleotide 2630 in exon 15. This mutation changes the Trp858
      codon (TGG) to a stop codon (TAG) (nonsense mutation). PCR-restriction analysis
      for the mutation revealed that the patient as well as his daughter was a
      heterozygote for the mutation, indicating that the patient was a compound
      heterozygote.

PMID- 8526945
TI  - Nitric oxide production by lymphatic endothelial cells in vitro.
AB  - The present study demonstrates that confluent monolayer cultures of lymphatic
      endothelial cells produce and secrete NO. Immunofluorescent studies showed that
      eNOS activity can be stimulated with Ca ionophore to enhance the production of
      NO. Cells exposed to LPS and various cytokines stimulated the production of iNOS
      which showed the greatest increase in activity at 4 hrs and declined at 18 and 24
      hrs. These studies provide evidence that, within the lymphatic vascular lumen,
      nitric oxide may be produced by the lymphatic endothelium which interact with
      various vasoactive substances to regulate lymphatic vascular tone. In addition,
      the production of NO by LEC may be important in the regulation of lymphatic
      vascular tone in order to more readily accommodate sudden fluctuations in lymph
      flow and pressure that normally occur during the process of lymph formation and
      propulsion.

PMID- 8526946
TI  - Polymerase chain reaction analysis of human papillomavirus in archival cervical
      cytologic smears.
AB  - We used a nested polymerase chain reaction (PCR) to study the presence of human
      papillomavirus (HPV) DNA in stained, archival cervical cytologic smears, where
      MY09/MY11 served as outer primers and GP5/GP6 as inner primers. It was found to
      give a higher positivity rate than PCR using the E1 degenerate consensus primers,
      where the sensitivity was decreased to 80%. It seemed optimal to use less sample
      DNA (0.5%) for the reaction; larger volumes resulted in decreased reactivity.
      Similarly, the presence of bovine serum albumin helped to improve the reactivity.
      The risk of cross-contamination did not seem to be a major obstacle to a valid
      analysis. The prevalence of HPV in normal smears was 10%, and in the high grade
      squamous intraepithelial lesion group it was 80%. Smears with cytologic evidence
      of HPV gave 100% positivity, while those containing cancer cells gave 80%. In
      patients whose Southern blot had demonstrated the presence of HPV, 87% of the
      simultaneously taken smears were also positive with nested PCR. Similarly, in
      those whose Southern blot analysis was negative, the corresponding smear was
      positive in 41%; this reactivity was associated with simultaneous squamous
      intraepithelial lesions. The prevalence values indicated that this analysis is
      both sensitive and specific and that it can be used to evaluate the performance
      of other diagnostic methods. The validity is sufficient to allow retrospective
      cohort studies of the natural history of HPV infections during carcinogenesis.

PMID- 8526947
TI  - Digitization of microcalcifications in breast radiographs. Correlation with
      pathologic data.
AB  - A series of 104 nonpalpable breast lesions detected by mammograms and containing
      microcalcifications were studied. Intraoperative radiographs of intact and sliced
      specimens were assessed, followed by microscopic diagnosis on frozen sections of
      areas containing microcalcifications. Microcalcifications detected on mammograms
      and radiographs of the specimens were digitized and evaluated in accordance with
      morphometric parameters, including the mean surface, shape factor, bend energy,
      envelope surface and total surface, total number and concentration of
      microcalcifications. Benign disorders, atypical hyperplasia and carcinomas
      accounted for 47.2%, 4.8% and 48% of the tissue lesions, respectively, but the
      disorders were most often heterogeneous and mixed. Most, but not all, parameters
      significantly correlated with the three types of radiographs, although
      radiographs of the sliced specimens provided images of the best quality. Only two
      parameters, mean size and bend energy, were significantly different (P = .008,
      .0036) in benign and malignant lesions. It is concluded that image analysis of
      digitized microcalcifications in radiographs may provide quantitative data
      helpful in mammogram interpretation.

PMID- 8526948
TI  - Comparison of nuclear area measurements carried out on normal and dysplastic oral
      smears.
AB  - We previously showed that quantitative cytology can help to detect oral cancer,
      not only at initial presentation but also in patients with unstable mucosa in
      whom recurrence has been detected prior to detection of a clinically obvious
      cancer. This has been due principally to the presence of a reduction in
      cytoplasmic area for Papanicolaou-stained cells and abnormal DNA distributions in
      Feulgen-stained nuclei collected from histologically confirmed dysplastic
      lesions. Furthermore, Feulgen-stained nuclei in oral smears that display abnormal
      DNA profiles appear to be larger than those in clinically normal smears, although
      an increase in nuclear area (NA) in Papanicolaou-stained smears is not always
      apparent. The aims of this study were to compare the mean NA values recorded for
      cells in Feulgen-stained smears with the values recorded for cells in
      Papanicolaou-stained smears collected from a selection of normal and abnormal
      sites to determine which of these smears produced mean NA values that correlated
      most closely with their DNA distributions. Forty patients with histologically
      confirmed epithelial dysplasia or invasive carcinoma and 20 patients with
      clinically normal mucosa were included in the study. NA values were obtained
      using image analysis. The mean NA values were obtained from the Feulgen-stained
      smears were significantly elevated when compared with mean NA values obtained
      from Papanicolaou-stained smears of dysplastic lesions and invasive carcinoma and
      for clinically normal smears collected from these patients. This elevation in
      mean nuclear size, for Feulgen-stained smears, correlated closely with DNA
      distribution.

PMID- 8526949
TI  - Morphologic and planimetric diagnosis of follicular thyroid lesions on fine
      needle aspiration cytology.
AB  - During 1989-1992, 2,729 fine needle aspiration biopsies were performed; 585 with
      histologic controls were reviewed. The aim of the study was to demonstrate the
      incidence of carcinoma in follicular-structured smears without nuclear
      enlargement, evaluated with planimetric techniques, and to suggest a new
      cytodiagnostic classification. Of 398 follicular-structured smears, 188 were
      colloid nodules, 38 were thyreocytic hyperplasias without nuclear atypia, 146
      were predominantly follicular lesions (PFL) and 26 were follicular lesions with
      nuclear pleomorphism. The last showed a high incidence of neoplasia (69.2%) and
      carcinoma (46.1%) and the largest planimetric values for nuclear area, perimeter
      and maximum diameter. The second and third categories showed only a difference in
      the incidence of benign neoplasms (32.9 vs. 15.8%). These results suggest that
      six months of expectant management might be useful in simple follicular lesions,
      whereas a follicular pattern with nuclear enlargement requires surgical treatment
      for the strong possibility of carcinoma.

PMID- 8526950
TI  - Computer-derived nuclear "grade" and breast cancer prognosis.
AB  - Visual assessments of nuclear grade are subjective yet still prognostically
      important. Now, computer-based analytical techniques can objectively and
      accurately measure size, shape and texture features, which constitute nuclear
      grade. The cell samples used in this study were obtained by fine needle
      aspiration (FNA) during the diagnosis of 187 consecutive patients with invasive
      breast cancer. Regions of FNA preparations to be analyzed were digitized and
      displayed on a computer monitor. Nuclei to be analyzed were roughly outlined by
      an operator using a mouse. Next, the computer generated a "snake" that precisely
      enclosed each designated nucleus. Ten nuclear features were then calculated for
      each nucleus based on these snakes. These results were analyzed statistically and
      by an inductive machine learning technique that we developed and call "recurrence
      surface approximation" (RSA). Both the statistical and RSA machine learning
      analyses demonstrated that computer-derived nuclear features are prognostically
      more important than are the classic prognostic features, tumor size and lymph
      node status.

PMID- 8526951
TI  - Flow cytometry of breast tumors. Relevance to clinicopathology and survival.
AB  - Nuclear DNA content and cell cycle distribution in fresh tissues from 40
      malignant and 10 benign breast tumors were assessed by flow cytometry using a DNA
      specific fluorochrome, 4,6-diamidino-2phenyl-indole hydrochloride. DNA indices
      (DIs) (relative DNA content of tumor cells with reference to normal cells, 4,6
      diamino-2phenyl-indole-hydrochloride ranged from 0.85 to 5.6 for malignant tumors
      and from 1.8 to 2.2 for benign tumors. Proliferating fraction (PF) (total cells
      in S and G2 + M phases) values were significantly higher in malignant tumors
      (35.4 +/- 14.75, mean +/- SD; P < .001) than in benign tumors (14.2 + 4.9) and
      adjacent normal tissues (6.6 + 2.73). DIs and cell cycle distribution correlated
      with clinicopathologic parameters, disease progression and survival. Four-year
      survival was greater in patients with a DI value of 1.8-2.2 as well as with SF
      values less than 10%.

PMID- 8526952
TI  - Quantitative DNA analysis in renal cell carcinoma. Comparison of flow and image
      cytometry.
AB  - In 70 renal cell carcinomas, nuclear DNA content was determined by means of flow
      cytometry (FCM) and image cytometry (ICM). The two methods produced comparable
      results as to DNA tumor ploidy (DNA tumor stemlines, DNA index): 14 of the tumors
      were tetraploid or aneuploid and 56 diploid. Results with the two methods were
      also comparable in a comparison of DNA ploidy with degree of tumor malignancy
      (tumor grade G1-3) and local tumor spread stage (pT stage). As a consequence,
      both methods appear suitable as means of determining DNA tumor ploidy and thus of
      formulating a prognosis in renal cell carcinoma. Renal cell carcinomas with
      diploid stemlines tend to be characterized by local growth, whereas tetraploid or
      aneuploid tumors show a tendency toward perirenal spread and venous invasion.

PMID- 8526953
TI  - Comparison between image and flow cytometry. A priori factors that influence
      technique.
AB  - Comparisons between flow cytometry (FCM) and image cytometry (ICM) have found a
      high concordance rate in pancreatic tissue, with some discrepancies between the
      two procedures. This study utilized 40 cases of chronic pancreatitis, primary
      pancreatic adenocarcinoma and metastatic pancreatic adenocarcinoma to determine
      the concordance rate between the two procedures. The reasons for discrepancies
      were identified and subsequently used to establish methods for a priori
      determination of which procedure to use. Using the FACSCAN flow cytometer and the
      CAS 200 on appropriately stained specimens that were disaggregated from 50-micron
      sections, we achieved a concordance rate of r = .878 (P < .01) after removing
      outliers. Thirty-one of 40 cases matched DNA content, and 9 cases had discrepant
      results. These discrepant cases were evaluated with factor analysis, in part
      because initial observations suggested that the variables evaluated could be
      combined into unifying concepts. The nine measured variables were compressed into
      three factors, which accounted for 68% of the variation observed between the two
      methods. Readily evaluated features, on a case-by-case basis, including
      tumor/nontumor ratios, accounted for the largest proportion of this variation.
      These findings suggest that tumor/nontumor cell ratios in hematoxylin-eosin
      stained sections may provide adequate a priori information to direct the choice
      of either FCM or ICM to measure DNA ploidy in pancreatic tissue.

PMID- 8526954
TI  - Volume-weighted mean nuclear volume and nuclear area in advanced ovarian
      carcinoma. An investigation of sampling methods, sample size and reproducibility.
AB  - The influence of sampling issues on the reproducibility of volume-weighted mean
      nuclear volume (mean v) and mean nuclear area (MNA) assessments in patients with
      International Federation of Gynecology and Obstetrics stage III and IV ovarian
      carcinoma was evaluated. Ten cases representing the whole range of MNA values
      were selected from a population of 131 cases. The MNA and mean v of the same
      tumor cell nuclei were determined in one session by switching between the
      stereologic module and the morphometric module of the video overlay program used.
      For both MNA and mean v in one series of measurements, tumor nuclei were sampled
      from the whole tumor area and in a second series from the most poorly
      differentiated part (the measurement area) in each section, thus giving four
      series of measurements per case. For all four series, 500 nuclei were point
      sampled from approximately 100 systematically randomly selected fields of vision,
      using the automated scanning stage controlled by the morphometry program. These
      large samples, containing 500 nuclei for each case, were regarded as
      representative in each case. To investigate the susceptibility of MNA and mean v
      to variance at lower sampling levels (fields, nuclei), a nested analysis of
      variance was performed. Then the influence of sample size and sampling method was
      evaluated by drawing subsets from these 500 nuclei in each case in three
      different ways (cluster, systematic or random) with four different sample sizes
      (50, 100, 125, 250). It was shown that for MNA assessed in the measurement area,
      the variance between patients contributed the most to the total
      variance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526955
TI  - [Severe pulmonary complications following venous air embolism in neurosurgical
      operations in sitting position--2 case reports].
AB  - The occurrence of air embolism during neurosurgical operations in sitting
      position is described in two cases. Besides the Doppler ultrasound evidence,
      relevant effects on the cardiopulmonary situation during surgery were observed,
      which in one case forced an early end of the operation. Postoperative management
      in both cases was complicated by a pulmonary oedema. In severe intraoperative
      cardiopulmonary complications in connection with venous air embolism, the
      existence of pulmonary oedema should be assumed. Confirmation of the diagnosis
      and the correct therapy depend upon frequent postoperative chest X-rays.

PMID- 8526956
TI  - [Treatment of postoperative pain with peridural administration of opioids].
AB  - The advantages and disadvantages associated with epidural opioids require careful
      selection of the opioid and its dose regimen. There is no ideal opioid available
      for epidural use. Comparative pharmacokinetic data help selection of the
      appropriate epidural opioid. Morphine (provided it is given in small doses and
      volumes) is very appropriate for epidural pain treatment, especially for longer
      periods of treatment, due to the excellent analgesia and very low systemic
      morphine concentrations. The faster onset of analgesia makes the epidural
      application of pethidine, alfentanil and fentanyl recommendable. However, due to
      the increased risk of respiratory depression during continuous treatment, these
      opioids should not be given over longer treatment periods. Epidural
      administration of methadon, sufentanil and buprenorphine cannot be recommended
      since the advantages over systemic use do not outweigh the risks. Epidural
      tramadol is useful in clinical routine if opioids are not available and
      supervision of the patient is not guaranteed, because the opioid is not
      restricted by law and has a low potential for central depressive effects.
      Nalbuphine and butorphanol should not be selected for epidural use until the
      benefit/risk ratio is defined. The safety of patients is paramount. If patients
      are harmed by inappropriate opioids or dose regimens, this will unjustly
      discredit a valuable treatment of postoperative pain.

PMID- 8526957
TI  - [Comparison of neuromuscular blockade by mivacurium and atracurium].
AB  - The aim of our randomized controlled study was to compare the neuromuscular
      characteristics of mivacurium and atracurium by evaluating the intubation
      conditions, intubation times, onset times and the duration of action of these two
      muscle relaxants using two different dosing principles. Forty-eight patients were
      included in this study. All patients were premedicated orally with 0.2 mg/kg
      diazepam. Anaesthesia was induced with 2.0 mg/kg propofol and 0.02 mg/kg
      alfentanil and maintained with 6 mg/kg/h propofol and 60% nitrous oxide in
      oxygen. Neuromuscular monitoring was carried out with supramaximal TOF
      stimulation (2 HZ) of the ulnar nerve every 10 seconds and recording of the
      mechanomyogram (MMG) (Myograph 2000, Biometer) at the adductor pollicis muscle.
      The patients of group 1 (n = 12) received an intubation dose of 0.15 mg/kg
      mivacurium (2 x ED95) and the patients of group 2 (n = 12) received a priming
      dose of 0.015 mg/kg mivacurium (20% of ED95) followed by an intubation dose of
      only 0.07 mg/kg mivacurium (ED95) two minutes later. The patients of group 3 (n =
      12) were intubated with 0.46 mg/kg atracurium (2 x ED95) and the patients of
      group 4 (n = 12) received a priming dose of 0.046 mg/kg atracurium (20% of ED95)
      and an intubation dose of 0.23 mg/kg atracurium (ED95) four minutes later. The
      patients were intubated under normocapnic conditions and following stabilisation
      of the palmar skin temperature after a 90% neuromuscular block (T1) had occurred.
      The intubation conditions were measured semiquantitatively using an intubation
      score.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526958
TI  - [Anesthesiologic problems in polytrauma patients].
AB  - The anaesthesiological problems concerning the primary care of multiple trauma
      patients are diverse. In addition to the specific anaesthesiological tasks such
      as protection of the vital functions by ventilation and volume replacement, the
      anaesthetist has further responsibilities. Often he has to coordinate primary
      diagnostics and care. He has charge of effective analgetic therapy, too. Taking
      all this into account, the specific and general duties require an anaesthetist
      with wide clinical experience in dealing with multiple trauma patients.

PMID- 8526959
TI  - [Early detection of opiate-induced respiratory depression in the postoperative
      phase].
AB  - We examined in 30 patients the efficacy of regular assessments of respiratory
      rate (every 15 minutes) and blood gas analysis (at 30, 60, 120, 180 minutes) and
      continuous monitoring via pulsoximeter and capnometer in recognizing early
      ventilatory problems. For postoperative analgesia the patients received randomly
      and double-blind patient-controlled intravenous or epidural analgesia with
      sufentanil. Within 15 minutes after the initial intravenous bolus injection of 15
      micrograms sufentanil respiratory depression occurred in 4 patients. This was
      alerted by the Oscar-CO2-Monitor and -Pulsoximeter. Oxygen saturation time
      patterns of pulsoximetry and blood gas analysis correlated significantly (p <
      0.001), although the mean values of the methods differed (NS). In contrast,
      carbon-dioxide pressure time patterns of capnometry and blood gas analysis
      correlated less significantly (p < 0.01) although the mean values of the methods
      correlated significantly (p < 0.01). Concomittant monitoring via pulsoximeter and
      capnometer is therefore superior to regulary assessments of respiratory rate and
      blood gas analysis and potentially useful for the clinical routine.

PMID- 8526960
TI  - [Documentation and information processing in clinical anesthesia].
AB  - Whereas anaesthesia recording was already introduced by Codman and Cushing in
      1894 and is now stipulated by law, work registration in anaesthesia and work
      comparison between departments of anaesthesia have only been built up in the last
      ten years. Based on the rapid development of computer technology specific
      solutions were found, ranging from simple software developments to complex on
      line monitor systems. The basic data bank published by the German Society of
      Anaesthesiology and Intensive Medicine represents a minimum of data, which can be
      added to at will. We report on our new anaesthesia record and corresponding
      software with computer supported manual data registration, which was developed at
      our clinic, taking into account state-of-the-art data processing and quality
      assurance. A new development, which includes on-line data processing with
      automatic data registration followed by graphic or numeric data print-out, is now
      presented by Datex. In combination with manual data input of all parameters of
      work registration, complete automatic anaesthesia recording can be achieved. The
      authors report on their first own experience with this system.

PMID- 8526961
TI  - [Interactions between renal and general hemodynamics in fentanyl, droperidol,
      ketamine, thiopental and in peridural anesthesia--animal studies].
AB  - The main focus of this paper is to show regulative interactions between cardiac
      index (CI) and renal blood flow (RBF) with various intravenous anaesthetics under
      steady state conditions. Several experimental series were carried out on dogs
      with the following anaesthetic doses (as given per hour and per kilogram body
      weight-h-1 x kg-1): fentanyl 50 micrograms, ketamine 4 and 10 mg, and thiopentone
      10 and 20 mg. The basic anaesthesia used was halothane (0.7 vol.%) in N2O/O2
      (ratio about 3:1), because renal function, renal autoregulation and
      responsiveness to renally effective drugs remain nearly unaltered by this
      anaesthetic procedure. The experimental set-up allowed separate evaluation of
      effects caused by basic anaesthesia, by intravenous anaesthetic under examination
      or by the combination of both. All physiological parameters, such as blood gas
      parameters, plasma electrolytes and intravasal volume were kept in normal range
      throughout the experiments. Under all anaesthetics studied, RBF reflects the
      situation of general metabolism especially of cardiac output, as long as
      sympathetic innervation of the kidneys remains unaltered. Especially the
      relationship between RBF and CI corresponds with regulative effects in situations
      without anaesthesia. Within the blood pressure range of autoregulation RBF is
      greater under ketamine than normal and smaller under fentanyl and etomidate,
      whereas all other anaesthetics applied show no effect on RBF. Functional
      "denervation" of the kidney by means of epidural anaesthesia is capable of
      terminating those effects caused centrally by opioids and transmitted by
      sympathetic nerves. Diuresis is increased by thiopentone and by ketamine, whereas
      fentanyl reduces it. The activity of the plasma renin level does not correspond
      with the degree of renal vascular resistance. The effect of each anaesthetic drug
      on RBF has principally to be taken as regulative adaptation to altered
      circulatory conditions. Increasing plasma renin levels are mainly a compensatory
      reaction following a decline in arterial blood pressure due to anaesthesia
      induced sympathicolysis. With regard to renal function, the additional use of
      epidural anaesthesia (functional "denervation" of the kidney) can be recommended
      especially for highly invasive surgical procedures to antagonize reduction of
      RBF, which is often induced sympathetically by pain or by commonly used
      anaesthetic drugs.

PMID- 8526962
TI  - [Improved climatization of anesthetic gases by modifying the Sulla 808 V
      anesthesia equipment].
AB  - Maintenance of a physiological airway climate is one of the goals of anaesthesia
      ventilation. This may be achieved by integration of heat and moisture exchangers
      (HME's) or--more economically--by reducing fresh gas flow rate down to the
      minimal-flow-range. Conventional bag-in-bottle ventilators with hanging bellows
      do not allow operation with minimal-flow-rates; flow reduction results sooner or
      later in a positive-negative-pressure ventilation pattern; especially so in
      patients suffering from COPD. This problem may be overcome by uncoupling fresh
      gas flow from tidal volume by means of integrating a reservoir bag and a special
      valve system to the circle system. This technique was hitherto restricted to high
      class anaesthetic workstations; since recently it became available as an update
      modification for the Sulla 808 VTM anaesthesia machine (Drager, Lubeck). With a
      setting previously described the effect of this modification on airway climate
      was investigated in a prospective, randomized clinical study. Twenty-four
      consenting patients were randomly assigned to be ventilated with either high (6.0
      L/min, n = 12) or minimal (0.6 L/min, n = 12) fresh gas flow rate. The time
      course of inspiratory temperature and humidity was measured over a period of 120
      minutes; water content was calculated from relative humidity and temperature. In
      the minimal-flow-group, already after 60 minutes a temperature of 28.6 +/- 0.9
      degrees C and a water content of 17.6 +/- 1.9 mg H2O/L were achieved (mean +/-
      SD).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526963
TI  - [Is preventive perioperative dopamine administration of value?].
AB  - Dopamine interacts in a dose dependent manner with three types of receptors: the
      alpha- and beta-adrenoceptors and specific dopaminergic receptors. Hence dopamine
      can exert direct and indirect renal effects. Stimulation of myocardial beta 1
      receptors causes an increase in cardiac output and a subsequent augmentation of
      renal blood flow. However, a major role of selective renal vasodilation in
      response to dopamine has been brought into question by recent studies. In
      addition, dopamine has been shown to decrease tubular transport of sodium and to
      produce sodium diuresis. This natriuresis may induce volume depletion with
      further deterioration of renal function. Expectations that low-dose dopamine
      could have a renal-sparing potential did not prove true. Prophylactic infusion of
      low-dose dopamine in patients undergoing aortic surgery, orthotopic liver
      grafting or renal transplantation failed to show a renal protective effect or an
      improved clinical outcome. The routine use of "renal-dose" dopamine therefore
      cannot be recommended. More attention must be paid to prevent or abolish prerenal
      causes of renal impairment. Basic measures as volume expansion, care of
      cardiocirculatory status and close monitoring of renal function are of special
      importance.

PMID- 8526964
TI  - [Comparison of various methods of anesthesia by plasma catecholamine
      determination].
AB  - Three different methods of anaesthesia (propofol or isoflurane with
      fentanyl/alfentanil, atracurium and O2/air or neurolept-anaesthesia with
      fentanyl, dehydrobenzperidol, pancuronium and N2O/O2) were compared in 64
      patients undergoing cardiac surgery before the start of extracorporeal
      circulation. Plasma catecholamine contents were determined and haemodynamic
      changes were recorded for the detection and quantification of sympathoadrenal
      responses to the typical points of stimulation (intubation, skin incision,
      sternotomy). The level of anaesthesia was held comparable by EEG monitoring
      (spectral edge frequencies between 8 and 12 Hz). Noradrenaline and adrenaline
      showed significantly lower values in the propofol group in comparison to the
      groups with isoflurane and neuroleptanaesthesia. The clearest increases in
      catecholamines were found in all groups before starting the extracorporeal
      circulation. There is no evident congruity between catecholamine levels and
      haemodynamic changes because of various interindividual differences. Derived
      values of haemodynamic parameters (integrals of blood pressure, rate pressure
      product and triple index) are more useful than single measurements for the
      description of circulatory reactions.

PMID- 8526965
TI  - [EEG changes during propofol-alfentanil-nitrous oxide anesthesia].
AB  - Blood pressure, heart rate and perspiration were and still are the only clinical
      signs for recognizing the depth of balanced anaesthesia in combination with
      muscle relaxants. Even experienced anaesthetists sometimes have difficulties in
      recognizing the necessary depth of anaesthesia using these parameters and in
      relatively rare cases the very unpleasant symptom of awareness occurs. Nowadays,
      processed EEG monitoring (pEEG) is used scientifically and also clinically for
      exact controlling of general anaesthesia. We report on our first experience with
      this method in 21 patients who were anaesthetized with propofol, alfentanil and
      nitrous oxide and relaxed with atracurium and whose depth of anaesthesia was
      carefully controlled by pEEG using the pEEG Monitor of Dragerwerke. The following
      parameters were recorded continuously: Spectral Edge Frequency (SEF) 50, SEF 90,
      SEF 95 and power between 8 and 20 Hz in relation to the power between 0 and 4 Hz
      (delta ratio). In agreement with other investigators we found that a sufficient
      depth of anaesthesia could be expected when the SEF 50 ranged between 2 and 6 Hz
      (4.9 +/- 0.9), the SEF 90 ranged between 10 and 13.5 Hz (11.9 +/- 0.6), the SEF
      95 ranged between 14 and 16 Hz (14.8 +/- 0.8) and the delta-ratio ranged between
      0.7 and 1.4 (1.1 +/- 0.2). Using this anaesthetic technique and a premedication
      with benzodiazepine, SEF 90 SEF 95 are the best parameters for monitoring the
      depth of anaesthesia. In one patient blood pressure and heart rate remained
      constant intraoperatively, but she described intensive dreams
      postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526966
TI  - [Patient-controlled analgesia (PCA) after urologic interventions].
AB  - Patient-controlled analgesia (PCA) is a well-accepted technique in postoperative
      pain management. We used PCA in three different protocols to find the optimum
      application form. Our study compared 100 patients with radical prostatectomy or
      transperitoneal tumor nephrectomy in three groups using piritramide. Group 1 (n =
      16) received 1.2 mg/h continuously and a 3 mg bolus with a lock-out time of 90
      min. Group 2 (n = 30) received 0.8 mg/h continuously and a 3 mg bolus with a lock
      out time of 60 min. Group 3 (n = 54) received the same continuous infusion, but
      the lock-out time was only 30 min. After 24 hours we evaluated the quality of
      analgesia using VAS scale. The quantity of piritramide was equal in all groups
      (35.1 mg). An average of seven bolus applications were made during the
      observation period. In 27.6% of the patients (group 1: 30.4%; group 2: 35.0%;
      group 3: 23.1%) the bolus demand was refused by programme. The analgesia level
      was satisfactory in each group, with a VAS value of 27. There was no respiratory
      depression observed. In conclusion, on-demand analgesia proved to be a good and
      practicable method in postoperative pain management. Although the dosage of
      piritramide was not different in the three groups, we recommend the protocol of
      group 3 because of the lower refusal of bolus application. Therefore, this seems
      to be the best patient-adapted application form. Even though respiratory
      complications in the group 3 scheme are not expected, monitoring of respiration
      and vigilance are recommended.

PMID- 8526967
TI  - Lack of cross-tolerance for hypophagia induced by DOI versus m-CPP suggests
      separate mediation by 5-HT2A and 5-HT2C receptors, respectively.
AB  - Intraperitoneal administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI) produced significant decreases in the first-hour food intake on day 1 and
      on day 2 relative to saline-treated animals. Complete tolerance developed to DOI
      induced hypophagia by day 3. However, there was no cross-tolerance to m
      chlorophenyl-piperazine (m-CPP)-induced hypophagia. Similarly, complete tolerance
      developed to m-CPP-induced hypophagia by day 3, but again there was no cross
      tolerance to DOI-induced hypophagia. These findings suggest that DOI and m-CPP
      induced hypophagia are mediated by different mechanisms, most likely by selective
      stimulation of 5-HT2A receptors by DOI and 5-HT2C receptors by m-CPP. The
      functional sensitivity changes did not parallel changes in hypothalamic [3H]
      mesulergine-labeled 5-HT2C receptors or [3H]-ketanserin-labeled 5-HT2A receptors
      following chronic m-CPP or DOI treatment, although both treatments significantly
      reduced 5-HT2A and 5-HT2C receptors in cortex. Thus, future studies investigating
      the effects of daily m-CPP and DOI administration on phosphoinositide hydrolysis
      or mRNA for 5-HT2C and 5-HT2A receptors in the hypothalamus might help explain
      the functional sensitivity changes observed in the present study.

PMID- 8526968
TI  - Cerebral glucose utilization in polysubstance abuse.
AB  - Regional cerebral glucose metabolism in subjects with histories of polysubstance
      abuse was compared to that in control subjects who were drawn from the same
      community. The substance abuse group showed lower absolute metabolic rates for
      glucose in lateral occipital gyrus and higher normalized metabolic rates in
      temporal and frontal areas, including orbitofrontal cortex. It is suggested that
      some patterns of brain function associated with polysubstance abuse may represent
      consequences of drug exposure, or they could reflect pre-existing differences
      that may be relevant to the etiology and maintenance of polysubstance abuse.

PMID- 8526969
TI  - The effects of a selective cAMP phosphodiesterase inhibitor, rolipram, on
      methamphetamine-induced behavior.
AB  - The effects of rolipram, a selective cAMP phosphodiesterase inhibitor, on
      locomotor activity, rearing, and stereotyped behavior (sniffing, repetitive head
      movements) induced by methamphetamine (MAP) over 1 hour were investigated in
      rats. Coadministration of rolipram (4 mg/kg IP) significantly attenuated the
      responses of locomotor activity, rearing and repetitive head movements to MAP
      (2,4 or 8 mg/kg IP). Rolipram (0.5, 1, 2, or 4 mg/kg IP) dose-dependently
      inhibited locomotor hyperactivity and rearing induced by 4 mg/kg of MAP. The
      rearing was completely inhibited by 4 mg/kg of rolipram, whereas the maximal
      inhibition of the locomotor hyperactivity was about 50%. However, rolipram did
      not alter MAP-induced sniffing and repetitive head movements. These results
      indicate that there is heterogeneity in the response of MAP-induced behavior to
      rolipram, suggesting that MAP-induced behavioral alteration may be partly
      regulated by cAMP levels in the brain.

PMID- 8526970
TI  - The effects of L-dihydroxyphenylalanine on alertness and mood in alpha-methyl
      para-tyrosine-treated healthy humans. Further evidence for the role of
      catecholamines in arousal and anxiety.
AB  - Treatment with alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis
      inhibitor, has been shown to produce pronounced increases in sleepiness and mild
      increases in negative mood and anxiety when administered to healthy male adults.
      The present study was conducted to ascertain whether these effects of AMPT are
      secondary to decreases in brain catecholamines or whether they represent
      nonspecific drug effects. Forty-one healthy males were randomized to one of four
      treatment groups. (1) Treatment with AMPT alone (AMPT/placebo); (2) treatment
      with AMPT plus L-dopa/carbidopa (AMPT plus L-dopa/carbidopa); (3) treatment with
      L-dopa/carbidopa alone (placebo plus L-dopa/carbidopa); or (4) treatment with
      placebo alone (placebo plus placebo). Repeated measures of alertness, mood, and
      anxiety were obtained over a three-day period of drug treatment and following
      drug discontinuation. As before, AMPT treatment led to increased sleepines. In
      addition, AMPT treatment led to decreased calmness, increased tension and anger,
      and a trend for increased depression. Replacement of catecholamine stores with L
      dopa reversed the effects of AMPT and was associated with a more rapid recovery
      from AMPT's effects. These findings indicate that AMPT's effects on alertness and
      anxiety are catecholamine-specific. Further, they provide additional evidence
      that catecholamines are involved in the regulation of normal states of arousal,
      and they are consistent with the view that brain catecholaminergic dysregulation
      is involved in pathological anxiety states.

PMID- 8526971
TI  - Blunted serotonergic responsivity in depressed inpatients.
AB  - We found a 38% lower maximal prolactin response to an oral challenge dose of 60
      mg of dl-fenfluramine relative to placebo in younger (< 30 years) depressed
      inpatients compared with the response in age-matched healthy controls (p < .03).
      Severity of depression did not correlate with prolactin response. Prolactin
      responses in older depressed patients (> or = 30 years) did not differ from older
      controls. Younger depressed patients differed from older depressed patients in
      terms of earlier age of onset of first lifetime episode of major depression,
      greater degree of suicidal intent during a recent suicide attempt, double the
      level of hopelessness on admission to hospital, and a higher rate of comorbid
      borderline personality disorder. A blunted prolactin response to fenfluramine may
      be interpreted as evidence for reduced serotonergic function in younger depressed
      patients and may underlie their observed greater suicidality and hopelessness.

PMID- 8526972
TI  - Uncoupling of the noradrenergic-hypothalamic-pituitary-adrenal axis in panic
      disorder patients.
AB  - In this paper the authors examine the interrelationship of both the noradrenergic
      (NA) system and the hypothalamic-pituitary-adrenal (HPA) axis and its
      implications for panic disorder (PD). Seventeen PD patients and 16 healthy
      volunteers were challenged orally 12 weeks apart with the alpha 2-agonist
      clonidine (13 healthy volunteers and 12 patients repeated the challenge). Between
      challenges, PD patients were treated with fluoxetine, with 10 of 12 improving at
      least moderately. Both during the acute phase of the illness and during the phase
      of pharmacological improvement, patients demonstrated a greater percentage of
      reductions of plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and plasma cortisol
      during clonidine challenge. We used correlational matrices to examine the
      relationship between the NA system, as reflected by plasma MHPG, and the HPA
      axis, as reflected by plasma cortisol measures. Healthy volunteers exhibited
      multiple significant "couplings" between either baseline or maximal decrease
      (delta max) of plasma MHPG, with either baseline or delta max plasma cortisol
      measures both within the first and second challenges and between the first and
      second challenges. In contrast, PD patients demonstrated "uncoupling" of the NA
      system and the HPA axis, with no significant correlations observed between either
      baseline and/or maximal decrease (delta max) measures of MHPG with the same
      cortisol measures for either the first or second challenge. The same uncoupling
      was observed for NA/HPA correlations between the first and second challenges.
      These data suggest that the hyperresponsivity to clonidine in PD patients
      persists during fluoxetine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8526973
TI  - Nimodipine increases CSF somatostatin in affectively ill patients.
AB  - Preliminary evidence suggests that nimodipine, an L-type calcium channel blocker,
      is effective in treating some patients with rapidly cycling affective disorders
      and some phases of Alzheimer's disease, i.e., two syndromes associated with
      transient or permanent reductions in cerebrospinal fluid (CSF) somatostatin,
      respectively. CSF somatostatin (SRIF) was measured in 14 affectively ill patients
      while they were medication-free and during chronic nimodipine treatment. CSF
      somatostatin significantly increased in patients during active nimodipine
      treatment compared with ones in the medication-free state. The current findings
      raise the possibility that nimodipine-induced increases in CSF somatostatin could
      potentially contribute to its spectrum of efficacy on neuropsychiatric disorders
      associated with cognitive or affective impairment. Further clinical and
      preclinical studies are indicated to elucidate the potential mechanisms involved
      in the elevation of CSF SRIF, whether it is reflected in regional changes in
      brain, and its possible relevance to nimodipine's clinical actions.

PMID- 8526974
TI  - Regional cortical anatomy and clozapine response in refractory schizophrenia.
AB  - Regional measures of cortical sulcal and ventricular enlargement on computed
      tomography scan were studied in a clinical sample of patients treated with
      clozapine. Cortical sulci were significantly enlarged in clozapine nonresponders
      compared to responders. The Clinical Global Impressions score at discharge was
      related to the size of the posterior frontal and lateral temporal sulci, with
      large sulci predicting a poorer response to clozapine treatment.

PMID- 8526975
TI  - Subanesthetic doses of ketamine stimulate psychosis in schizophrenia.
AB  - We administered ketamine to schizophrenic individuals in a double-blind, placebo
      controlled design using a range of subanesthetic doses (0.1, 0.3, and 0.5 mg/kg)
      to evaluate the nature, dose characteristics, time course, and neuroleptic
      modulation of N-methyl-D-aspartate (NMDA) antagonist action on mental status in
      schizophrenia. Ketamine induced a dose-related, short (< 30 minutes) worsening in
      mental status in the haloperidol-treated condition, reflected by a significant
      increase in BPRS total score for the 0.3 mg/kg (p = .005) and 0.5 mg/kg (p = .01)
      challenges. Positive symptoms (hallucinations, delusions, thought disorder), not
      negative symptoms accounted for these changes. These ketamine-induced psychotic
      symptoms were strikingly reminiscent of the subject's symptoms during active
      episodes of their illness. Results from six patients who were retested in the
      same design after being neuroleptic-free for 4 weeks failed to indicate that
      haloperidol blocks ketamine-induced psychosis. Several subjects evidenced delayed
      or prolonged (8-24 hours) psychotomimetic effects such as worsening of psychosis
      with visual hallucinations. These data suggest that antagonism of NMDA-sensitive
      glutamatergic transmission in brain exacerbates symptoms of schizophrenia.

PMID- 8526976
TI  - Evaluation and monitoring of action on alcohol. Targets, indicators and
      monitoring and reporting systems for action on alcohol.

PMID- 8526977
TI  - Composition of the ovarian fluid in 4 salmonid species: Oncorhynchus mykiss,
      Salmo trutta f lacustris, Salvelinus alpinus and Hucho hucho.
AB  - The ovarian fluid of rainbow trout (Oncorhynchus mykiss), charr (Salvelinus
      alpinus), lake trout (Salmo trutta f lacustris) and Danube salmon (Hucho hucho)
      was analyzed for its inorganic and organic composition. The qualitative
      composition of the ovarian fluid of the investigated species was similar, but
      significant quantitative differences were found. The following components were
      determined: sodium 106.6-142.2 mmol/l, potassium 1.7-2.7 mmol/l, calcium 0.45
      0.61 mmol/l, osmolality 256.4-291.6 mosmol/kg, pH 8.4-8.8, glucose 1,698-4,195
      mumol/l, fructose 17-399 mumol/l, lactate 34-227 mumol/l, cholesterol 650-1,230
      mumol/l, phosphatidylcholine 0.25-3.0 mumol/l, lysophosphatidylcholine 10-100
      mumol/l, choline 0-1.1 mumol/l, protein 95.0-278.4 mg/100 ml. Arginine, cystine,
      glycine, histidine, lysine, proline, serine, tyrosine and valine were the free
      amino acids occurring in concentrations of more than 10 mumol/l. Activities of
      alkaline phosphatase (200-6,000 mumol substrate/l/h), lactate dehydrogenase (9
      690 mumol substrate/l/h), beta-D-glucuronidase (70-410 mumol substrate/l/h),
      proteases (140-215 mumol/l/h with collagen substrate, 25-90 mumol/h/l with
      gelatine substrate) and acid phosphatase (100-130 mumol substrate/l/h) were
      measured, but not the glucose-6-phosphate dehydrogenase and alpha-glucosidases
      activities.

PMID- 8526978
TI  - [Physiology of intestinal absorption of phosphorus in animals].
AB  - Intestinal absorption of inorganic phosphorus. In most mammalian species
      inorganic phosphorus (P) is absorbed at the duodenal and jejunal level. However
      in horses some P is absorbed from the large intestine, whereas in ruminant
      animals some absorption also takes place in the forestomachs. The structure of
      the putative phosphate-sodium carrier of the brush border from enterocytes still
      awaits identification. P absorption is modulated both by endocrine (calcitriol,
      triiodothyronine) and nutritional factors (minerals of the diet, chemical form of
      phosphorus). Regulation of salivary P secretion, intestinal absorption of P in
      ruminants, and its adaptation to diets high or low in P are still poorly
      understood. Such studies would probably help to decrease the cost of P
      supplementation in farm animals.

PMID- 8526979
TI  - [Analysis of protein nutrient reserves of the clitellum and cocoon albumin in
      Eisenia fetida Sav (Annelida Oligochaeta). Demonstration of a glycolipoprotein
      comparable to vitellogenin].
AB  - In the clitella of Eisenia fetida, the amount of total proteins decreased
      dramatically during puberty. In contrast, the level of soluble proteins increased
      during the same period. In the cocoons, the increase of total proteins and
      soluble proteins corresponded to the development of the embryos. Among the
      soluble proteins of the mature clitellum, 3 major proteins (A, B and C) were
      separated by electrophoresis: A, glycolipoproteinic (molecular weight = 450 kDa),
      B, glycoproteic (MW = 350 kDa) and C, also glycoproteinic (MW = 150 kDa). Only A
      was present in the cocoons during all the stages of development. Although this
      protein is not incorporated in the oocyte, it has the same characteristics as a
      typical vitellogenin. After denaturation of the soluble proteins, 4 polypeptides
      were obtained. Two of them, a and c, are involved in the making of this
      'vitellogenin'.

PMID- 8526980
TI  - Effects of moderate fat intake with different n-3 fatty acid sources and n-6/n-3
      ratios on serum and structural lipids in rats.
AB  - The aim of this study was to compare the effects of dietary polyunsaturated fatty
      acids (PUFA) on serum and membrane lipids in rats fed diets containing moderate
      levels of fats (6% by weight). Control rats received enough PUFA to prevent any
      deficiency. Experimental rats were fed linseed oil, salmon oil, or sunflower oil.
      After 8 weeks of feeding, fasting serum triacylglycerol and cholesterol levels
      were not altered in the linseed oil group. In contrast, in the salmon oil group,
      serum cholesterol was lowered by 58% (P < 0.05) and the specific binding of
      heterologous LDL to liver plasma membrane was reduced by 31% (P < 0.05).
      Unexpectedly, serum triacylglycerol levels were not significantly lowered (-14%)
      whereas they decreased (-32%; P < 0.05) in the sunflower oil group. Oleic acid,
      which has a stimulating effect on triacylglycerol synthesis and secretion, was
      less incorporated in serum and liver plasma membrane in rats fed sunflower oil
      than in rats fed other dietary lipids. This finding suggests that the effect of
      dietary sunflower oil was partly mediated by the reduction of oleic acid
      available for triacylglycerol synthesis.

PMID- 8526981
TI  - Reassessing the manipulation of protein synthesis by rumen microbes.
AB  - Protein synthesis by rumen microbes plays an important role in ruminant
      nutrition. Microbial proteins that are not recycled flow out of the rumen and
      account for more than 50% of the total proteins entering the intestines.
      Determination of microbial nitrogen in digesta is based on the isolation of a
      representative sample of rumen microbes and on the use of specific markers
      (purine bases, RNA, 15N incorporation). This review discusses the reliability of
      microbial markers and examines current methods for assessing differences in
      turnover rate and microbial composition among liquid and particulate
      compartments. Four groups of factors acting on microbial synthesis, which are
      also adaptable to farm conditions, are considered: I) modification of protozoal
      population; II) modification of liquid and solid phase kinetics in the rumen;
      III) balance in the components of the diet; and IV) probiotics. The effects of
      these factors are discussed, considering their feasibility and their usefulness
      for the host.

PMID- 8526982
TI  - [Sugars and lipids of the clitellum and cocoon albumin in Eisenia fetida Sav
      (Annelida Oligochaeta)].
AB  - Biochemical methods were used to analyze the glucidic and lipidic components of
      the clitellar epithelium and the cocoon's albumen in Eisenia fetida. In the
      clitellum, the sugar concentration increased dramatically (about 5-fold) during
      differentiation. The assays showed increases in several monosaccharides during
      puberty. In addition, glucose was prominent in immature clitella, whereas mannose
      was the main sugar in the mature ones. About 50% of the dry weight of recently
      deposited cocoons was carbohydrates. The sugar concentration decreased in the
      albumen as hatching approached. The amount of total lipids in the clitellum
      increased during maturation. The levels of neutral lipids, however varied very
      little. Phospholipids began at low levels at the beginning of differentiation,
      and increased dramatically thereafter. The amount of fatty acids in the clitellar
      epithelium reached a maximum during the submature stage. Large amounts of fatty
      acids were stored in the cocoon. Palmitic, stearic, oleic and vaccenic acids were
      preponderant in both the clitellum and cocoon.

PMID- 8526983
TI  - Effect of short photoperiodic cycles on male genital tract and testicular
      parameters in male goats (Capra hircus).
AB  - This study was performed in adult male goats in which seasonal variations were
      abolished by rapid alternations of long days and short days. These treatments
      have been shown previously to prevent seasonal changes in the hypothalamo
      pituitary axis and to maintain testis weight and sperm production at a high
      level. The experimental groups were exposed for 3 years to an alternation of
      either a 1 month short (16 h dark; 8 h light) and 1 month long (16 L; 8 D)
      photoperiod (2 month cycle; n = 5) or of a 2 month short and 2 month long
      photoperiod (4 month cycle; n = 4). The control groups were maintained in natural
      photoperiodic conditions (45 degrees N) and goats were slaughtered in the non
      breeding season (end of April RS; n = 5) at the same period as light-treated
      bucks, or in the breeding season (end of September BS; n = 6). The total weight
      of the testes, the length and mean diameter of the seminiferous tubules of light
      treated goats were similar to those in the breeding season, and higher than those
      in the non-breeding season. The total number of A0 spermatogonia was increased by
      light treatments as compared to control goats in the breeding and non-breeding
      season. The daily production of A1 spermatogonia, leptonene primary spermatocytes
      and round spermatids in light-treated goats was maintained at the peak breeding
      season level. The intra-testicular concentration of testosterone, total volumes
      of intertubular tissue and of Leydig cells, and the number of Leydig cells per
      testis did not differ between groups. Although the mean cross-sectional area of
      Leydig cells in light-treated goats was similar to this area in non-breeding
      season goats, it was significantly lower than that of breeding season goats. In
      conclusion, the rapid alternation of short and long days allowed an increase in
      all the germ cells from the A0 spermatogonia onwards, which was responsible for
      the maintenance of high spermatogenetic activity of light-treated goats.

PMID- 8526984
TI  - In vitro effect of the gonad of Helix aspersa (Mollusca) on galactogen synthesis
      in the albumen gland of either mated or virgin snails.
AB  - The gonad of Helix aspersa contains a factor which can stimulate in a dose
      dependent manner galactogen synthesis in albumen gland explants cultured in
      vitro. The stimulatory activity appears to be greater when the gonad is
      predominantly male than when it is predominantly female. The albumen gland of
      virgin snails does not respond in vitro to the gonadal influence. The receptivity
      of the albumen gland to the galactogen synthesis stimulating effect of the gonad
      is increased after the first and second mating. It decreases at the third mating
      in correlation with the increase of the albumen gland maturation index.

PMID- 8526985
TI  - Ultrastructural immunolocalisation of histones (H2B, H3, H4), transition protein
      (TP1) and protamine in rabbit spermatids and spermatozoa nuclei. Relation to
      condensation of the chromatin.
AB  - The histones H2B, H3 and H4, the transition protein TP1 and protamine were
      localised using ultrastructural immunocytochemistry in nuclei of rabbit
      spermatids and spermatozoa. Histones are present in round spermatid nuclei and
      are lost during the elongation of nuclei. TP1 and protamine appear simultaneously
      in all nuclei during this period. TP1 is located at the periphery of chromatin
      cords, while protamine seems to be located at random in the same cords. TP1 is
      lost in most elongated spermatids during step 13 of spermiogenesis, and the
      protamine stays in all sperm nuclei. TP1 remains present in some old spermatids
      and ejaculated spermatozoa. In the rabbit, 3-6% of sperm nuclei decondense
      spontaneously. Most are characterised by a retention of TP1. Respective roles of
      TP1 and the protamine in spermatid nuclear condensation are discussed.

PMID- 8526986
TI  - Co-expression of mannose-ligand and non-nuclear progesterone receptors on motile
      human sperm identifies an acrosome-reaction inducible subpopulation.
AB  - PROBLEM: To determine whether surface expression of receptors for progesterone
      and mannose can be used to identify spermatozoa likely to undergo an acrosome
      reaction after zona binding and to compare the reactivity of these receptors with
      naturally occurring sperm head-directed anti-sperm antibodies (ASAs). METHOD:
      Progesterone binding sites on the surface of fresh and capacitated motile human
      sperm in relation to acrosome status were visualized using a cell-impermeant
      progesterone. Free progesterone and/or mannose ligands were compared for percent
      sperm binding and ability to induce an acrosome reaction. Western blots of sperm
      proteins localized to the plasma membrane and surface proteins precipitated
      following passive transfer of serum ASAs were probed with progesterone
      horseradish peroxidase. The effects of the same ASAs on ligand binding and on the
      induced acrosome reaction were examined. RESULTS: The two receptors are located
      in close proximity on a subset of capacitated motile sperm and are coordinately
      cleared from the plasma membrane overlying the acrosomal cap prior to exocytosis.
      The surface appearance of functional binding sites for each ligand, however, is
      regulated by different mechanisms and the progesterone receptor alone is
      specifically precipitated by ASAs. Passive transfer of ASAs to capacitated sperm
      selectively inhibits the progesterone-stimulated acrosome reaction but not the
      ionomycin-induced acrosome reaction or the ability of sperm to bind mannose
      ligands. CONCLUSIONS: Sperm from fertile donors incubated under capacitating
      conditions in vitro can be subdivided into acrosome reaction inducible and
      noninducible subpopulations on the basis of the co-expression or total absence of
      these receptors. The combined data indicate that reaction of sperm surface
      progesterone receptors with ASAs contributes to the acrosome reaction
      insufficiency observed in anti-sperm immune infertility.

PMID- 8526987
TI  - Can the immunobead assay for detecting sperm antibodies in fresh samples be
      reproduced in cryopreserved/thawed human spermatozoa?
AB  - PROBLEM: To evaluate the reproducibility of the Immunobead Assay (IBA) on sperm
      samples before and after cryopreservation. METHOD: Sperm samples (fresh and post
      thaw) from known antibody negative donors (N = 20) were evaluated for percent
      immunobead binding by IBA following incubation with known antibody-positive
      serum. RESULTS: In both fresh and thawed negative samples, the mean sperm head
      binding was 0.5% +/- 0.5, the mean sperm tail binding was 2.0% +/- 2.0 and the
      mean sperm head-tail binding was 3.0% +/- 2.0 for IgG, IgA and IgM type
      antibodies, respectively. The same samples exposed to positive sera showed 40.0%
      +/- 10.0 mean head binding, 7.0% +/- 8.0 mean tail binding and 47.0% +/- 11.0
      mean head-tail binding. CONCLUSIONS: IBA is highly reproducible for detecting
      sperm antibodies in both fresh and cryopreserved/thawed samples of human
      spermatozoa.

PMID- 8526988
TI  - Sperm immobilizing antibodies interfere with sperm migration from the uterine
      cavity through the fallopian tubes.
AB  - PROBLEM: It is well known that sperm migration in cervical mucus is impaired by
      sperm immobilizing antibodies secreted in the mucus. However, it is not clear yet
      whether sperm migration from the uterine cavity through the fallopian tubes to
      the peritoneal cavity is impaired by sperm immobilizing antibodies. To test the
      possible impairment of sperm migration in the tubes, laparoscopic examinations
      were carried out and the presence of motile sperm in the peritoneal fluid after
      intra-uterine insemination was investigated. METHOD: Peritoneal sperm recovery
      tests were performed in 28 infertile women with sperm immobilizing antibodies in
      their sera, and the results were compared with those in 322 infertile women
      without the antibodies. Both the sperm immobilizing antibody titers (SI50) and
      complement activities (C'H50) in peritoneal fluid were compared with those in
      patients' sera. In some experiments, the supernatant of the peritoneal fluid was
      used as a source of complement for the sperm immobilization tests instead of
      guinea pig serum. RESULTS: Among couples with normal semen characteristics by the
      criteria of WHO, sperm recovery in the peritoneal fluid was observed in only 3
      (11.1%) of 27 patients with sperm immobilizing antibodies, compared with 72
      (34.0%) of 212 patients without the antibodies (P < 0.025). The antibody titers
      of the patients with the sperm recovery were very low by the quantitative sperm
      immobilization test. In most patients, a similar amount of sperm immobilizing
      antibodies was present in the peritoneal fluid and the sera. Though the
      complement activities in the peritoneal fluid were less than those in sera, the
      former were still found to be sufficient to immobilize sperm in vivo.
      CONCLUSIONS: These results suggest that the complement-dependent sperm
      immobilizing antibodies could interfere with sperm migration in the female
      genital tract at the level of the fallopian tubes.

PMID- 8526989
TI  - Anamnestic development of lymphocytic infiltration in murine experimental
      autoimmune oophoritis is primarily localized in the stroma and theca.
AB  - PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces autoimmune
      oophoritis and ovarian failure in B6A mice. These mice develop high-titer
      autoantibodies specific to oocytes, and ultimately the ovaries become fibrotic
      and devoid of primordial follicles. These findings implicate the oocyte as a
      primary target of the autoimmune process. However, in previous work we
      demonstrated that in developing disease the lymphocytic infiltration was confined
      to the stroma and theca, and not found involving oocytes. Here, we investigate
      the possibility that lymphocytic infiltration involving oocytes develops as part
      of end-stage disease. METHOD: We transplanted normal syngeneic ovaries to B6A
      mice with confirmed autoimmune ovarian failure, and, as a control, to normal
      oophorectomized mice. We then defined the time course and histologic distribution
      of lymphocytic infiltration in the transplanted ovaries. Lymphocytes were
      identified by morphology with the aid of an immunohistochemical leukocyte marker
      (CD45). RESULTS: Autoimmune oophoritis developed by 7 days after transplantation
      to the NTX3 mice. Compared to control mice, in these mice we found significantly
      increased stromal and thecal lymphocytic infiltration. In no case did we observe
      lymphocytic infiltration involving oocytes. CONCLUSIONS: Our findings agree with
      our previous report and suggest that the ovarian failure in this model is not
      mediated by a direct lymphocytic attack against intact oocytes. Other immune
      mediated mechanisms are responsible. The paradoxical development of high-titer
      oocyte-specific antibodies despite the stromal and thecal location of the
      lymphocytic infiltration remains to be explained.

PMID- 8526990
TI  - Murine experimental autoimmune oophoritis develops independently of gonadotropin
      stimulation and is primarily localized in the stroma and theca.
AB  - PROBLEM: Neonatal thymectomy performed on day 3 of life (NTX3) induces
      experimental autoimmune oophoritis in certain strains of mice. The disease has
      its onset around the time of the first estrous, suggesting the process may be
      gonadotropin dependent. Furthermore, one study reported that gonadotropin
      stimulation exacerbated the ovarian lymphocytic infiltration in NTX3 mice. Here
      we examine the possibility that gonadotropin stimulation of the ovary plays a
      role in the development of post-thymectomy autoimmune oophoritis. METHOD: Using
      immunohistochemistry we defined the time course and histologic distribution of
      the post-thymectomy ovarian lymphocytic infiltration that develops in B6A mice
      ([C57BL6 X A/J]F1). We detected ovarian leukocytes using a monoclonal antibody
      against mouse CD45/T200 and counted those positive staining cells that had the
      morphologic appearance of lymphocytes. We then treated NTX3 mice to determine if
      gonadotropin stimulation could exacerbate the disease or cause the disease to
      appear earlier. We also treated NTX3 mice to determine if gonadotropin
      suppression could reduce the severity of the disease. RESULTS: Ovarian
      lymphocytic infiltration was observed as early as 3 weeks after thymectomy, and,
      during the course of the disease, was primarily located in the stroma and theca.
      Gonadotropin stimulation did not exacerbate existing disease or induce an earlier
      onset of severe disease. Furthermore, gonadotropin suppression did not reduce the
      degree of lymphocytic infiltration or oocyte destruction. CONCLUSIONS: Our
      findings suggest that murine experimental autoimmune oophoritis develops
      independently of gonadotropin stimulation of the ovary.

PMID- 8526991
TI  - Interleukin-1 beta induces cyclooxygenase-2 in cultured human decidual cells.
AB  - PROBLEM: The purpose of this study was to examine the hypothesis that interleukin
      1 beta (IL-1 beta)-elicited increases in decidual prostaglandin E2 and F2 alpha
      (PGE2 and PGF2 alpha) biosynthesis are due to the de novo expression of the
      inducible isoform of cyclooxygenase (i.e., COX-2). METHOD: Primary human decidual
      cell cultures were established from term placentas delivered by cesarean section.
      After 8 days in vitro, when the cultures secreted immunoreactive prolactin, the
      cells were incubated for 24 h in serum-free medium, and then challenged with IL-1
      beta from 1 to 48 h. PGE2 and PGF2 alpha content in the media were measured by
      specific radioimmunoassays. RESULTS: IL-1 beta stimulated a time-dependent
      enhancement in PGE2 and PGF2 alpha production, with PGF2 alpha synthesis
      predominating over PGE2. IL-1 beta also induced a dose-dependent increase in the
      output of both arachidonic acid metabolites. When Northern blots of IL-1 beta
      treated and control cells were probed with cDNAs encoding either COX-1 or COX-2
      isoforms or an oligonucleotide probe encoding a portion of the human beta-actin,
      we detected a time- and dose-dependent increase in the steady-state levels of COX
      2, but not COX-1 or beta-actin mRNA transcripts. Moreover, the expression of COX
      2 mRNA in IL-1 beta-stimulated cells was superinduced by preincubation with
      cycloheximide, but completely abolished by actinomycin D. CONCLUSIONS: Taken
      together, the data suggest that COX-2 mRNA expression is largely responsible for
      the robust increase in PG formation seen in IL-1 beta-treated decidual cells.

PMID- 8526992
TI  - Immunohistochemical localization of C9 neoantigen and the terminal complement
      inhibitory protein CD59 in human endometrium.
AB  - PROBLEM: Human endometrium expresses complement components, receptors, and
      regulatory proteins, many of which appear to be expressed in a hormone-dependent
      manner. Whether terminal complement components are also present in the
      endometrium is unknown. CD59, a broadly expressed protein that blocks association
      of C9 with C8 in the membrane attack complex, is localized in reproductive tissue
      to human spermatozoa, seminal plasma, amniotic fluid, and placenta. The present
      study examines human endometrium for the presence of CD59 and terminal complement
      proteins. METHOD: Endometrial biopsies were obtained from six normal women from
      various phases of the menstrual cycle and analyzed by immunohistochemistry, using
      MEM-43 anti-human CD59 and anti-human SC5b-9 murine monoclonal antibodies and the
      immunoperoxidase technique. RESULTS: Both CD59 protein and SC5b-9 (C9 neoantigen)
      were demonstrated to be present in endometrial glandular epithelium throughout
      the menstrual cycle. No specific staining was demonstrated in the stromal
      compartment. CONCLUSION: CD59 protein and terminal complement proteins are
      expressed in glandular epithelial cells of normal human endometrium, in both
      proliferative and luteal phases, suggesting that expression is not hormonally
      dependent. These analyses further support the presence of a functionally active
      complement system in normal human endometrium.

PMID- 8526993
TI  - Detection of antiendometrial antibodies in sera of patients with endometriosis by
      dual-colored, double-labeling immunohistochemical method and western blot.
AB  - PROBLEM: This study was undertaken to determine whether specific binding
      activities against endometrial proteins in sera of patients with endometriosis
      are detectable and, if so, to identify endometrial antigens involved in
      autoimmunity in endometriosis. METHOD: Sera from 33 patients with endometriosis
      and 20 cord sera (controls) were tested against endometria of patients and their
      protein extracts by dual-colored, double-labeling immunohistochemical method, and
      Western blotting. RESULTS: Antiendometrial binding activities were detected in
      sera of 2 (10.0%) control patients and 13 (48.2%) patients with endometriosis by
      the immunohistochemical method. Endogenous immunoglobulin G (IgG) binding to
      endometrial proteins had molecular weights (MW) of 26, 28, 54, 85, 107 and 116
      kDa. Most sera of both control and patients showed reactivity against endometrial
      proteins with MW of 34, 36, 56 and 77 kDa. However, there were specific IgG
      autoantibodies reactive against the endometrial proteins of 71, 92, and 103 kDa
      in sera of 55.2% (16/29) of patients but not in the control sera. Over 80%
      (10/12) of patients' sera with binding activities detectable by the
      immunohistochemical method also tested positive by Western blot analysis.
      CONCLUSIONS: These data show that specific IgG antibodies reactive against
      endometrial antigens are detectable in sera from some patients with
      endometriosis.

PMID- 8526994
TI  - Preimplantation factor (PIF) predicts subsequent pregnancy loss.
AB  - PROBLEM: To evaluate the ability of preimplantation factor (PIF) measured in the
      lymphocyte/platelet binding assay (LPBA) to predict subsequent spontaneous
      abortion. METHOD: Serum from 57 women experiencing first trimester pregnancy
      losses were studied using the LPBA (46 women conceived after in vitro
      fertilization and embryo transfer for treatment of infertility and 11 with a
      history of unexplained recurrent spontaneous abortion conceived spontaneously).
      The assay employs a combination of heat inactivated sera with donor O+
      lymphocytes and platelets, complement and an antibody against CD2. Chromosome
      analysis was performed on 32 of the abortuses. Results of PIF assay were compared
      between karyotypically normal and abnormal abortuses. RESULTS: PIF assay was
      negative in all 57 women at the time of abortion. Among 12 karyotypically normal
      abortuses only 1 woman (8%) had an initial positive PIF, 11 (92%) had negative
      PIF. Serial PIF assays were performed on 15 women. PIF assay became negative a
      minimum of two weeks prior to demonstration of intrauterine demise at a time when
      hCG concentrations remained elevated. A trend to subnormal was seen in women with
      normal when compared to those with abnormal abortus karyotype, but the numbers
      were too small to reach statistical significance (P = 0.09). CONCLUSION:
      Measurement of PIF throughout the first trimester of pregnancy predicts
      subsequent pregnancy loss.

PMID- 8526995
TI  - Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral
      blood lymphocytes in pregnant women with recurrent pregnancy losses.
AB  - PROBLEM: To analyze immunophenotypic profiles of peripheral blood and humoral
      autoimmune responses in women with a history of recurrent spontaneous abortions
      (RSA). METHOD: Peripheral blood lymphocyte subsets by flow cytometry and
      autoantibodies to phospholipids and nuclear components by ELISA were measured in
      nonpregnant and pregnant women with RSA of unknown etiology. Thirty-five pregnant
      and eighty-one nonpregnant women with RSA were studied. Seventeen nonpregnant and
      twenty-two pregnant normal controls were included. RESULTS: Natural killer (NK)
      cells (CD56+) were significantly elevated in nonpregnant women with RSA as
      compared with nonpregnant controls. Pregnant women with RSA demonstrated
      significantly increased NK (CD56+, CD56+/CD16+) and B cells (CD19+) as compared
      with pregnant controls. Women who miscarried the index pregnancy demonstrated
      significantly lower CD3+ cells in comparison with normal controls. Women with RSA
      and antiphospholipid antibodies showed significantly elevated NK cells when
      compared with women without antiphospholipid antibodies. Women with
      autoantibodies to nuclear components demonstrated significantly elevated
      CD19+/CD5+ cells when compared to women without autoantibodies to nuclear
      components. CONCLUSIONS: Women with RSA demonstrate an abnormal cellular immune
      response by increasing peripheral natural killer cells and B cells as compared
      with normal controls.

PMID- 8526996
TI  - Effects of citalopram, a synthetic serotonin uptake inhibitor, on indoleamine and
      catecholamine concentrations in the cerebrospinal fluid of freely moving rats.
AB  - We studied changes in the concentrations of 5-hydroxytryptamine (5-HT), other
      indoleamines, and catecholamines in the cerebrospinal fluid (CSF) of freely
      moving rats that had been administered citalopram, +/-1-[3-
      (Dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydro-5-isobenzo
      furancarbonitrile hydrobromide), a selective inhibitor of 5-HT uptake. In a
      microdialysis experiment, the intracerebral extracellular free 5-HT increased
      significantly, peaking 60 to 90 min after citalopram (30 mg/kg p.o.) was
      administered. The 5-HT concentrations in CSF from the cisterna magna increased
      significantly, reaching a maximum 6 hours after a single dose of citalopram (30
      mg/kg p.o.) was given. Six hours after this dose, the CSF 5-HT concentration in
      the cisterna magna was significantly increased, and the 5-hydroxyindoleacetic
      acid (5-HIAA) concentration was significantly decreased. There were non
      significant changes in the other indoleamines (tryptophan, 5-hydroxytryptophan,
      and kynurenine) and in the catecholamines (dopamine, homovanillic acid,
      normetanephrine, and 3-methoxy-4-hydroxyphenethyleneglycol). The 5-HT/tryptophan
      ratio was correlated significantly with the kynurenine/tryptophan ratio before
      treatment with citalopram (r = 0.81, p = 0.051), indicative that there is
      coordination of the serotonin and kynurenine pathways in normal rats. In the
      animals posttreatment there was no such correlation, suggesting that the changes
      in 5-HT are independent of the kynurenine system at least within the 6 hours
      postreatment. These CSF results appear to reflect selective inhibition of 5-HT
      uptake in brain tissues by citalopram that is not associated with changes in
      catecholamines.

PMID- 8526997
TI  - Indoleamine concentrations in cerebrospinal fluid from patients with Alzheimer
      type and Binswanger type dementias before and after administration of citalopram,
      a synthetic serotonin uptake inhibitor.
AB  - We studied changes in the concentrations of serotonin (5-HT), kynurenine, and
      other indoleamines in the cerebrospinal fluid of patients with Alzheimer type
      dementia (ATD) and those with Binswanger type vascular dementia (VDBT), and
      changes in these indoleamine concentrations 2 weeks after administration of
      citalopram, a 5-HT uptake inhibitor. The concentrations of total 5-HT (p < 0.005)
      and kynurenine (p < 0.005) were significantly decreased in ATD patients in
      comparison to those of the controls. After citalopram administration, there was a
      remarkable increase in 5-HT concentration (249%, p < 0.0001) and a significant
      decrease in 5-HIAA concentration (22%, p < 0.02). In the VDBT patients, only 5-HT
      showed a significant decrease (p < 0.005) in comparison to the control values. It
      also increased significantly (214%) after citalopram administration. The 5
      HT/tryptophan and kynurenine/tryptophan ratios were not correlated for the
      controls, but did significantly for the ATD and VDBT patients; after citalopram
      treatment, the increase in 5-HT/tryptophan was correlated significantly with that
      of kynurenine/tryptophan for ATD, but not for VDBT. These results suggest that
      both the serotonin and kynurenine pathways are impaired in ATD; whereas, the
      serotonin pathway alone is in VDBT, and that these impairments are ameliorated by
      the administration of citalopram.

PMID- 8526998
TI  - The effects of d-cycloserine, a partial agonist at the glycine binding site, on
      spatial learning and working memory in scopolamine-treated rats.
AB  - The present study investigated the effect of d-cycloserine, a partial agonist at
      the glycine binding site on NMDA receptor complex, on the performance of
      scopolamine-treated adult rats in a water maze task assessing spatial learning
      and in a delayed non-matching to position task assessing working memory in a
      spatial context. In the spatial learning task, scopolamine (0.4 mg/kg, i.p.)
      impaired acquisition (increased escape latency and distance) and increased
      swimming speed of rats. D-cycloserine (1.0 mg/kg, i.p.) reversed the deficits in
      acquisition performance but not the increases in behavioral activity. In the
      working memory task, scopolamine (0.2 mg/kg, i.p.) produced deficits on
      nonmnemonic rather than on mnemonic performance factors; scopolamine delay
      independently decreased the percent correct responses and reduced behavioral
      activity of rats. D-cycloserine (1.0, 3.0 and 10 mg/kg, i.p.) did not reverse
      these performance deficits. When administered alone, the moderate to higher doses
      of d-cycloserine had no effects on working memory but the lower dose produced
      slight deficits in mnemonic performance factors; the 1.0 mg/kg dose delay
      dependently decreased the percent correct responses without affecting behavioral
      activity of rats. In the water maze task, d-cycloserine had no effects on
      acquisition performance or behavioral activity of rats. These results suggest
      that acute, systemic administration of d-cycloserine does not improve spatial
      learning or working memory. However, at appropriate doses this agent may be
      efficacious in disease states of central cholinergic hypofunction since 1.0 mg/kg
      d-cycloserine was able to reverse the scopolamine-induced deficits in
      acquisition.

PMID- 8526999
TI  - Centrally-administered AMPA antagonists increase locomotion in parkinsonian rats.
AB  - It was shown in the present study that three antagonists of the alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor, including
      2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), 1-(4-aminophenyl)-4
      methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) and 6-(1H-imidazole
      1-yl)-7-nitro-2,3-(1H, 4H)-quinoxalinedione (YM90K), caused marked reversal of
      akinesia when administered into the entopeduncular nucleus of rats rendered
      parkinsonian by bilateral substantia nigra pars compacta lesion. These data
      suggest that centrally active AMPA antagonists may have therapeutic utility in
      the treatment of idiopathic Parkinson's disease.

PMID- 8527000
TI  - The expression of proenkephalin and prodynorphin genes and the induction of c-fos
      gene by dopaminergic drugs are not altered in the straitum of MPTP-treated mice.
AB  - The expression of proenkephalin (PENK), prodynorphin (PDYN) and c-fos genes was
      studied in the striatum of C57B1/6 mice treated with 1-methyl-4-phenyl-1,2,3,6,
      tetrahydropyridine (MPTP), which are used as a rodent model of Parkinson's
      disease (PD). Two weeks after systemic administration of MPTP (2 x 40 mg/kg, s.c.
      18h apart), the lesion of the substantia nigra (SN) could be visualised by loss
      of the nigral tyrosine hydroxylase (TH) mRNA hybridization signal and by a 91%
      decrease in striatal dopamine levels. The levels of PENK and PDYN mRNAs were not
      significantly changed in the striatum of the lesioned mice, as compared to non
      treated controls. The induction of the immediate early gene c-fos by the dopamine
      D2 receptor antagonist haloperidol was not altered, while the selective D1
      receptor agonist SKF 38393 failed to induce c-fos in the striatum of MPTP-treated
      mice. These results are in contrast to the data concerning rats with the 6
      hydroxydopamine (6-OHDA) lesion of the SN, which serve as another rodent model of
      PD. In the striata of 6-OHDA-lesioned rats, PENK gene is upregulated, PDYN gene
      is down-regulated and the induction of c-fos gene by D2 receptor antagonists is
      abolished, whereas selective D1 receptor agonists induce c-fos gene, which does
      not occur in non-lesioned rats. We presume that the lack of influence of the MPTP
      lesion in mice on the striatal gene expression was mainly caused by insufficient
      dopamine depletion in the striatum, which could not be increased in this model.
      The importance of the changes observed in 6-OHDA-lesioned rats has been discussed
      in the context of the mouse and primate MPTP models of PD.

PMID- 8527001
TI  - Neuropsychological characteristics of parkinsonian patients with lateralized
      motor impairment.
AB  - Parkinsonians with predominantly unilateral signs provide an interesting
      experimental means to evaluate if asymmetric nigro-striatal degeneration may
      affect neuropsychological functions. The aim of our study was to establish if the
      side of onset of idiopathic Parkinson's disease, right (PDR) or left (PDL),
      determines a selective pattern of cognitive performances. Furthermore, we
      verified if PDR and PDL groups show a different frequency of dementia. PDR and
      PDL patients with at least seven years of disease duration, matched for age,
      schooling, severity of extrapyramidal symptomatology and index of lateralization,
      were evaluated by using an extensive neuropsychological battery aimed at
      assessing hemispheric cognitive asymmetries. Current side of greater motor
      impairment was the same as the one affected at the onset of the disease. Only
      subtle differences in the profile of neuropsychological dysfunction emerged from
      the comparison of PDR and PDL subjects. Moreover, the number of parkinsonians
      showing dementia syndrome was the same in both groups. Our results suggest that
      the side of onset of motor impairment does not significantly influence the
      cognitive performances in PD. Subcortical anatomic and/or functional asymmetries
      seem to play a less important role in the intellectual functions than in motor
      activities.

PMID- 8527002
TI  - Effect of age and disease duration on parkinsonian motor scores under levodopa
      therapy.
AB  - One hundred and fifty patients suffering from Parkinson's disease were analysed
      for the expression of the motor symptoms during optimum response to levodopa
      therapy (subscale III of the Unified-Parkinson's Disease Rating Scale). Patients
      were grouped according to age (< or = 64, 65-74, > or = 75 years). Disease
      duration and daily levodopa dosage were similar in the three groups. Pooled
      residual scores for posture and gait impairment (PGI), tremor (T), rigidity (R)
      and distal motor impairment (DMI; hand and foot movements) increased with age
      (Kruskal-Wallis ANOVA). The parkinsonian scores were significantly higher than
      the scores of 150 age-matched normal controls (Mann-Whitney U test). The
      differences between the patients' scores and the scores of the age-matched
      controls increased with age. In spite of a significant increase in the daily
      levodopa dosage with disease duration (linear regression), PGI aggravated age
      dependently, and DMI age-independently with symptom duration (Spearman rank
      correlation). In contrast, T and R did not increase with disease duration.

PMID- 8527003
TI  - CSF somatostatin increase in patients with early parkinsonian syndrome.
AB  - Somatostatin-like immunoreactivity levels (SLI) in cerebrospinal fluid (CSF) were
      determined in twenty-three patients with untreated parkinsonian syndrome (15 with
      Idiopathic Parkinson's disease (IPD) and 8 with other forms of parkinsonism) at
      the moment of clinical diagnosis (mean duration of disease 1.1 +/- 0.2 years),
      and in 26 subjects without neurological symptoms. None of the IPD patients had a
      diagnosis of dementia at the moment of inclusion in the study. CSF-SLI content
      was found to be significantly higher in patients with parkinsonian syndrome
      (107.9 +/- 9.8 pg/ml) than in control subjects (73.5 +/- 8.4 pg/ml). The increase
      was also significant when controls were compared with IPD patients. In addition,
      a positive correlation between SLI and homovanillic acid was found in CSF of all
      patients. A test of learning memory was used to evaluate the mental state of
      patients and a significant increase in CSF-somatostatin levels was observed in
      patients with Idiopathic Parkinson's disease and severe affectation of memory.
      These results indicate that in the early steps of untreated parkinsonian
      syndrome, somatostatin concentration in cerebrospinal fluid may increase,
      probably due to the neurodegenerative depletion of somatostatin from striatal or
      cortical neurons.

PMID- 8527004
TI  - Modality dependent changes in event-related potentials correlate with specific
      cognitive functions in nondemented patients with Parkinson's disease.
AB  - The relationship between event-related potentials (ERPs) and cognitive
      functioning was studied in patients with Parkinson's Disease (PD) but without
      dementia. Auditory and visual stimuli were used; 30 subjects participated in the
      auditory study and 20 in the visual study. Patient groups did not differ with
      respect to gender, age, education, illness duration, and level of cognitive
      functioning. Visual stimuli were 2.3 cpd sinusoidal grating patterns randomly
      presented in an oddball paradigm (oblique vs. vertical spatial orientation).
      Auditory stimuli were tones presented at 70 dB SPL at a rate of 1.1/second, also
      using the oddball paradigm (1.5K vs. 1K tones). All patients were given
      neuropsychological tests to measure verbal fluency, memory, visual spatial
      perception, and abstract reasoning. P300 and N200 abnormalities correlated with a
      number of these measures, such that longer ERP latencies were related to lower
      scores on tests of cognitive functioning. Patterns of results suggest that
      auditory and visual ERPs correlate with different subsets of neuropsychological
      functions in nondemented PD patients and that N200 may provide a new metric for
      clinical use.

PMID- 8527005
TI  - Does reserpine induce parkinsonian rigidity?
AB  - The aim of the study was to find out whether the reserpine-induced rigidity is
      similar to that seen in parkinsonism. Simultaneous measurements of the muscle
      resistance of the hind foot to passive bending and stretching in the ankle joint,
      as well as of the electromyographic (EMG) activity of the gastrocnemius and
      tibialis anterior muscles of rats were carried out. Reserpine was injected in a
      dose of 10 mg/kg alone or with alpha-methyl-p-tyrosine (250 mg/kg) 1, 4 and 27.5
      h before the measurements. Reserpine increased the muscle resistance of the rat's
      hind leg to passive movements. That effect was the strongest at 1-2 h after the
      injections, and diminished markedly afterwards. The rigidity was accompanied with
      an increase in the resting, as well as in the stretch-induced short- and long
      latency EMG activity in the gastrocnemius muscle. However, the intensity of the
      latter symptom did not change for a long period of time, which seems to correlate
      with the striatal dopamine depletion. The results suggest that the reserpine
      increased EMG activity is a good model of parkinsonian rigidity.

PMID- 8527006
TI  - Monoamine oxidase A-inhibiting components of urinary tribulin: purification and
      identification.
AB  - The endogenous monoamine oxidase (MAO) inhibitory activity, termed tribulin,
      contains several components. We have previously identified one of them, isatin,
      which is a selective inhibitor of MAO B. In the present study we have purified
      several further components of human urinary tribulin which act as selective
      inhibitors of MAO A. They have been identified by gas chromatography-mass
      spectrometry (GC-MS) as ethyl indole-3-acetate (and/or methyl indole-3
      propionate), methyl indole-3-acetate and ethyl 4-hydroxyphenylacetate. IC50
      values for MAO A were found to be 44 microM (105 microM for methyl indole-3
      propionate), 88 microM and 120 microM, respectively, whilst those for MAO B were
      each greater than 1 mM. The artificial formation of these esters was excluded by
      carrying the parent acids, from which they are presumably synthesized, through
      the purification procedure. As tribulin output is increased during stress or
      anxiety, these results point to a possible role for tryptamine and tyramine
      pathways in such disorders.

PMID- 8527007
TI  - Human transplacental transfer of carbidopa/levodopa.
AB  - A paucity of information is available concerning the use of levodopa and
      carbidopa during pregnancy. Particularly lacking is whether these agents cross
      the placenta and whether levodopa undergoes metabolism in the fetus. The present
      study carried out in aborted fetal tissues demonstrates that levodopa crosses the
      placental barrier and suggests that it may be metabolized in fetal tissues,
      including the brain and spinal cord. The possibility exists that early exposure
      to levodopa or dopamine may alter the normal neuronal development in the fetus,
      and caution in the use of levodopa during pregnancy should be observed.

PMID- 8527008
TI  - The use of famotidine in the treatment of Parkinson's disease: a pilot study.
AB  - Seven patients with idiopathic Parkinson's disease were enrolled in a ten week
      study to evaluate the efficacy of famotidine, an histamine H2-antagonist, in the
      treatment of bradyphrenia. Patients received famotidine 80 mg/day for a period of
      six weeks and were evaluated with neuropsychological tests. Overall, patients
      demonstrated improvement in variables measured. Some patients also reported an
      improvement in their motor symptoms.

PMID- 8527009
TI  - Regional cerebral blood flow measured by 99mTc-HMPAO SPECT differs in subgroups
      of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might
      have impact in patients' response to different treatment strategies. We designed
      a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To
      identify AD subtypes, we performed a cluster analysis including performance on
      memory, language, visuospatial, praxic, and executive functions. The rCBF
      measured by 99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35
      patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex
      matched healthy cognitively intact controls. AD patients were at the early stage
      of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6).
      The cluster analysis revealed two AD subgroups: AD1 (N = 12) and AD2 (N = 23).
      The subgroups did not differ in age, sex, or global clinical severity as assessed
      by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally
      impaired memory. The AD2 group was inferior to the AD1 group on verbal,
      visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF
      ratios in the temporal and parietal cortices and the amygdala compared to
      controls. The AD2 group differed from controls in the rCBF ratios of frontal,
      temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral
      and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients,
      the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several
      significant correlations were found between decreases rCBF ratios and impairment
      of memory and other cognitive functions. In conclusion, a cluster analysis on
      neuropsychological test performance identified two AD subgroups that differed on
      the neuropsychological profile and on the rCBF in spite of similar global
      clinical severity.

PMID- 8527010
TI  - How important is therapeutic drug monitoring in the prediction and avoidance of
      adverse reactions?

PMID- 8527011
TI  - Thalidomide: rationale for renewed use in immunological disorders.
AB  - Despite its inherent teratogenic risk, thalidomide has over the years proven to
      be of clinical use in a small number of mainly immunological diseases (e.g.
      erythema nodosum leprosum, Behcet's syndrome and rheumatoid arthritis). The mode
      of action of thalidomide is still poorly understood. Recent research has shown a
      decrease in tumour necrosis factor-alpha (TNF alpha) during thalidomide treatment
      in several settings. Others have found altered expression of adhesion molecules.
      Currently, the most interesting new fields of application are the prevention and
      treatment of graft-versus-host disease in allogeneic bone marrow transplantation
      and the treatment of aphthous ulceration in HIV-positive patients. Contraceptive
      measures must be instituted in women receiving thalidomide, and careful
      monitoring for neurological adverse effects is required in all patients.

PMID- 8527012
TI  - CNS adverse events associated with antimalarial agents. Fact or fiction?
AB  - CNS adverse drug events are dramatic, and case reports have influenced clinical
      opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus
      establishing causality is difficult. CNS events are associated with the quinoline
      and artemisinin derivatives. Chloroquine, once considered too toxic for humans,
      has been the antimalarial of choice for 40 years. While a range of serious CNS
      effects have been documented during chloroquine therapy, the incidence is unclear
      (extrapyramidal symptoms occur with an incidence of 1 in 5000). Amodiaquine has a
      higher incidence of mild CNS effects than chloroquine. Mefloquine therapy causes
      dose-related transient dizziness. Serious CNS events during mefloquine therapy
      occur in 1:1200 Asians and 1:200 Caucasians/Africans. Risk factors include
      dosage, concomitant drug use/interactions, previous history of a CNS event and
      disease severity. Retreatment (within a month) increases the risk in Asians 7
      fold. Studies indicate that the frequency of serious CNS events with mefloquine
      prophylaxis (1:10,000) is similar to that with chloroquine (1:13,600). Quinine
      causes cinchonism at standard therapeutic doses. High-tone hearing loss occurs,
      but irreversible auditory or ocular effects are very rare. The artemisinin
      derivatives are associated with dose-dependent brain lesions in rodent, canine
      and nonhuman primates. At low doses, histological injury has been demonstrated,
      without clinical neurological signs. No significant toxicity has been reported in
      humans. Other antimalarial drugs are seldom associated with CNS adverse events.
      Data do not suggest a need to diminish the correct use of the quinoline
      derivatives. Irreversible effects are extremely rare and usually associated with
      overdosing or prior history of a serious CNS event. Concomitant therapeutic use
      of 2 drugs from the same family, or retreatment with the same drug, should be
      avoided. Onset of drug-associated serious CNS events requires drug
      discontinuation and future avoidance of the drug.

PMID- 8527013
TI  - A risk-benefit assessment of cisapride in the treatment of gastrointestinal
      disorders.
AB  - Cisapride is a substituted benzamide compound that stimulates motor activity in
      all segments of the gastrointestinal tract by enhancing the release of
      acetylcholine from the enteric nervous system. Cisapride is administered orally
      in the treatment of gastro-oesophageal reflux disease, functional dyspepsia,
      gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic
      constipation. In gastro-oesophageal reflux disease in both adults and children,
      cisapride provides symptomatic improvement and mucosal healing. Long term
      treatment with cisapride is effective in the prevention of relapse of
      oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in
      patients with gastroparesis of various origins. Unlike domperidone and
      metoclopramide, long term administration of cisapride seems to result in
      persistently enhanced gastric emptying. Cisapride is also effective in improving
      symptoms in patients with functional dyspepsia. In comparative studies in
      patients with functional dyspepsia, cisapride was at least as effective as
      metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride
      increases stool frequency and reduces laxative consumption in patients with
      idiopathic constipation. Severe cases of slow transit constipation seem
      refractory to cisapride. Clinical studies also indicate that cisapride might be
      effective in the treatment of chronic intestinal pseudo-obstruction,
      postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical
      studies are warranted to define the role of cisapride in these conditions. The
      dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride
      is generally well tolerated, both during short and long term treatment. In
      children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4
      times daily.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527014
TI  - Drug interactions of clinical importance. An updated guide.

PMID- 8527015
TI  - Pharmacoepidemiology in practice. Current status and future trends.
AB  - Pharmacoepidemiology is the application of epidemiological reasoning, methods and
      knowledge to the study of the uses and effects (beneficial and adverse) of drugs
      in human populations. As referred to by the term 'pharmacoepidemiology', the
      discipline now enters into its second decade, although its origins go back to the
      beginnings of this century. This article reviews the opinions of leading
      pharmacoepidemiologists on the scope and prospects for pharmacoepidemiology, and
      summarises the most important challenges that the discipline faces on its way
      towards the next century. The future of pharmacoepidemiology requires the
      development of research methods more able to cope with the specific problems
      posed by the study of drugs, notably the issue of confounding by indication and
      the ability to adjust accurately for severity of disease. Capacity building
      should also continue during the next years; training of professionals, the
      optimisation of computerised databases for research purposes and their joint use
      with more traditional epidemiological methods are major challenges. From a public
      health perspective, a critical task is to assess the impact that vaccines and
      drugs have on the overall patterns of disease in well defined populations.

PMID- 8527016
TI  - When a randomised controlled trial is needed to assess drug safety. The case of
      paediatric ibuprofen.
AB  - Drugs are frequently made available for use before risks of rare but serious
      reactions have been identified and quantified. While this situation may be
      acceptable for drugs used to treat serious conditions, greater information on
      safety is needed for drugs used to treat less serious conditions, and
      particularly those medications available without prescription. Spontaneous
      reports and observational studies can provide useful data in most instances, but
      nonrandomised studies are inadequate in the presence of confounding by indication
      (i.e. when patients treated with a drug differ in their underlying risk of
      adverse outcome from patients given alternate treatments, independent of the
      effect of the drug). Such is the case in the US with regard to the use of
      paediatric ibuprofen as an antipyretic. In this setting, a rigorous and large
      randomised controlled trial is needed to provide valid and statistically stable
      risk estimates. A trial of this kind is a feasible way to develop clinically
      meaningful data on safety with respect to rare but serious adverse reactions.

PMID- 8527017
TI  - Slow-acting antirheumatic drugs. Drug interactions of clinical significance.
AB  - The slow-acting antirheumatic drugs (SAARDs) are being used in an increasing
      proportion of patients with rheumatoid arthritis (RA). The potential toxicity of
      each drug is well recognised. Many patients with RA will be on other medications
      and the potential for adverse drug interactions with SAARDs is not so well
      publicised. There have, over the years, been numerous reports of possible drug
      interactions with SAARDs but few of these are clinically relevant. It is,
      however, vitally important that the physician is aware of a number of potentially
      life-threatening interactions, particularly those associated with methotrexate.
      The SAARDs are a very useful group of drugs for the treatment of RA and, by being
      aware of their potential toxicity and drug interactions, hopefully they can be
      used safely and effectively.

PMID- 8527018
TI  - Adverse effects of chemotherapeutic agents used in tropical medicine.
AB  - Traditionally, many of the chemotherapeutic agents used in tropical medicine have
      possessed limited efficacy and serious adverse effects. This scenario has been
      revolutionised by the introduction into clinical parasitology of the
      benzimidazole compounds, praziquantel (and other schistosomicidal agents) and
      ivermectin for helminthiases, and the 5-nitroimidazoles for protozoan infections.
      An effective armamentarium against Plasmodium spp. infections, especially P.
      falciparum, is receding as widespread multiple drug resistance becomes
      commonplace. Although management of several more exotic parasitic infections,
      including trypanosomiasis, leishmaniasis and onchocerciasis remains
      unsatisfactory, several newer and relatively non-toxic preparations (including
      eflornithine and ivermectin) are now available, and offer optimism. However,
      there remains a very long way to go before a single preparation is available to
      combat all major protozoan and/or helminthic infections; such an agent would also
      need to be 100% effective when given as a single dose, safe not only in the
      healthy adult but also during pregnancy and lactation, stable at high ambient
      temperature and relatively low in cost.

PMID- 8527019
TI  - Drug-induced thyroid disorders.
AB  - Many drugs can interfere with biochemical tests of thyroid functions by
      interfering with the synthesis, transport and metabolism of thyroid hormones, or
      by altering the synthesis and secretion of thyrotrophin (thyroid-stimulating
      hormone; TSH). Only rarely, however, do these effects cause overt, clinically
      apparent thyroid disease. Lithium therapy causes overt hypothyroidism in 5 to 15%
      of patients, and goitre in up to 37%. Thyroid function tests should be performed
      prior to initiating lithium therapy, and at 6-monthly intervals thereafter.
      Iodine and iodine-containing drugs (e.g. radiographic contrast media, iodinated
      glycerol and amiodarone) can have profound and variable effects on thyroid
      function.

PMID- 8527020
TI  - Drug-induced severe skin reactions. Incidence, management and prevention.
AB  - Severe skin adverse drug reactions can result in death, but the rate of such
      events is fortunately low. The incidences of Stevens-Johnson syndrome and toxic
      epidermal necrolysis range from 1.2 to 6 per million per year and 0.4 to 1.2 per
      million per year, respectively. Stevens-Johnson syndrome is fatal in about 5% and
      toxic epidermal necrolysis in 30% of cases. Drugs implicated in these diseases
      are the sulphonamides, anticonvulsants, allopurinol, pyrazolone derivatives,
      oxicams and chlormezanone. The principles of symptomatic treatment are the same
      as for burns, and patients with extensive skin detachment should be transferred
      to an intensive care unit or a burn centre. Hypersensitivity syndrome is
      characterised by mucocutaneous eruption and fever with frequent lymphadenopathy,
      hepatitis and eosinophilia. Drugs implicated are mainly anticonvulsants and
      sulphonamides. The mortality rate of such a reaction has been estimated to be
      about 8%. Corticosteroid therapy has been widely used in hypersensitivity
      syndrome, despite the lack of controlled studies. Drug-induced vasculitis and
      serum sickness may also be life-threatening when the kidney, liver,
      gastrointestinal tract or nervous system are involved. In angioedema, congestion
      may involve mucous membranes and therefore impair swallowing and ventilation.
      Drugs associated with angioedema include penicillins, radiographic contrast
      agents and ACE inhibitors. Severe forms of angioedema necessitate epinephrine
      (adrenaline) subcutaneous injection and possibly resuscitative efforts.
      Corticosteroids and/or antihistamines are used to block or reduce prolonged or
      late phase reactions. Prompt recognition and withdrawal of the suspected drug is
      essential in severe drug-induced skin reactions.

PMID- 8527021
TI  - How 'safe' are antioxidant vitamins?
AB  - Interest in a putative disease-preventive role for the so-called antioxidant
      nutrients derives from a large body of evidence suggesting that oxidative damage
      is a contributing cause of many life-shortening diseases. Since their use is an
      otherwise healthy population, it is important that such agents be virtually free
      of toxicity. The agents of most interest are alpha-tocopherol (vitamin E),
      ascorbic acid (vitamin C) and beta-carotene. When used for disease prevention,
      the doses given are several-fold greater the Recommended Dietary Allowance (RDA),
      the latter being based on amounts necessary for the prevention of classic
      deficiency conditions recognised decades ago. alpha-Tocopherol, ascorbic acid and
      beta-carotene are remarkably well tolerated and free from toxicity. Consequently,
      they are well suited for testing as preventive agents, since their use does not
      require any toxicity monitoring except in unusual circumstances. An example of
      the latter would be in patients who are vitamin K deficient, perhaps through
      anticoagulation with drugs such as warfarin, in which case use of high doses of
      alpha-tocopherol may increase the bleeding tendency.

PMID- 8527022
TI  - Conformational analysis of the Ca(2+)-bound opioid peptides: implications for
      ligand-receptor interaction.
AB  - Based on our earlier proposal on the role of Ca2+ in ligand-receptor recognition
      and the demonstration of the similarity of the Ca(2+)-bound forms of Met
      enkephalin and morphine (Zhorov, B.S. and Ananthanarayanan, V.S., FEBS Lett. 354,
      131-134 (1994)) we have undertaken the conformational analysis of a series of the
      Ca(2+)-bound opioid peptides aiming to find their conformations matching Ca(2+)
      bound morphine. A Monte Carlo-with-energy-minimization method was used to
      calculate 14 opioid peptides in the presence of Ca2+. Low-energy conformations of
      the Ca2+ complexes of peptides with high mu-affinity were found to resemble
      closely morphine-Ca2+ complex. In contrast, the Ca2+ complexes of peptides with
      low mu-affinity did not. The results are relevant for understanding the structure
      activity relations of opioid receptor ligands.

PMID- 8527023
TI  - Crystal structures of four morpholino-doxorubicin anticancer drugs complexed with
      d(CGTACG) and d(CGATCG): implications in drug-DNA crosslink.
AB  - Among the new generations of anthracycline drugs, morpholino-doxorubicin (MDox)
      and its derivative have unusually potent activity when compared with the parent
      doxorubicin. 3"-Cyano-morpholino-doxorubicin (CN-MDox) has been suggested to form
      a covalent crosslink to DNA, although the exact mode of interactions remains
      unclear. To establish the structural basis of this crosslink, we carried out X
      ray diffraction analyses of the complexes between four different morpholino
      doxorubicins (i.e., MDox, CN-MDox, (R)- and (S)-2"-methoxy-morpholino-Dox
      (MMDox)) and two DNA hexamers CGTACG and CGATCG. Their crystal data are similar
      to other Dau/Dox complexes with space group P4(1)2(1)2,a = b approximately 28 A,
      c approximately 53 A. The refined structures at approximately 1.8 A resolution
      revealed that two drug molecules bind to the duplex with the aglycons
      intercalated between the CpG steps with their N3'-morpholino-daunosamines in the
      minor groove. The morpholino moiety is flexible and may adopt different
      conformations dependent on the sequence context. The O1" atoms of the two
      morpholino groups in the drug-DNA complexes are in van der Waals contact. The
      structural results suggest possible crosslinking mechanism of CN-MDox. It is
      worth pointing out that by linking two piperazinyl- or piperidinyl-doxorubicins
      at the 1" positions a new type of bis-doxorubicin derivatives may be synthesized
      which may bind to a hexanucleotide sequence with some specificity.

PMID- 8527024
TI  - Spectroscopic studies on the interaction of three partially hydrogenated acridine
      dyes with calf thymus DNA and their structural comparison.
AB  - The interaction of three partially hydrogenated acridine dyes (acridine I,
      acridine II and acridine III) with calf thymus DNA was studied using
      spectrophotometric and spectrofluorometric methods. This paper presents the
      evidence for the formation of complexes between acridine I, II and III with calf
      thymus DNA. From the results of this studies various binding parameters were
      evaluated. The binding constant for acridine I and acridine III ranged from 2.1
      to 4.4 x 10(5) M-1 for the P/D ratio from 4.29 to 0.56 while for acridine II this
      constant increased from 0.78 to 2.26 x 10(5) M-1 for the P/D ratio 12 to 2.38 and
      decreased to 1.47 at P/D ratio 1.34. The Scatchard analysis indicated a
      cooperative binding of acridine II to calf thymus DNA as compared to acridine I
      and III. A red shift in the visible absorption bands for dye DNA complexes (for
      acridine I = 8, acridine II = 7, and acridine III = 9 nm) suggested an
      electronically coupled interaction mode for the dyes. It is concluded that
      acridine II interacted stronger with calf thymus DNA than acridine I or III. The
      results are interpreted in terms of their crystal structures and also with the
      already reported DNA binder structures.

PMID- 8527025
TI  - Statistical description of nucleic acid secondary structure folding.
AB  - A simple statistical model describing the folding of nucleic acids is proposed.
      For long sequences the real configuration of the secondary structure is a quasi
      equilibrium state that cannot be characterised by minimal free energy. This is
      because the time required to achieve complete thermal equilibrium considerably
      exceeds the life-time of the molecule. The formation of the secondary structure
      is represented as a random walk process in the space of all possible molecular
      configurations. The quasi equilibrium structure is obtained by successive linking
      and disruptions of helix segments with probabilities determined by the rate
      constants of corresponding unimolecular reactions. The probabilities of
      configurations consisting of all possible compatible helices are calculated.
      Structures of some t-RNAs and ribosomal RNAs are analysed.

PMID- 8527026
TI  - Thermodynamic and structural features of cooperative interactions in tandem
      oligonucleotide derivatives arranged at the complementary template. Chemical
      modification data.
AB  - General equations are derived for the limit yield [PZ] infinity of the
      intraduplex reaction between reactive oligonucleotide derivative X bearing p-(N-2
      chloroethyl-N-methyl-amino)phenyl residue and oligonucleotide target P
      encompassing the sequence complementary to X in the presence of one or two
      oligonucleotide effectors E1 and E2. The latters form the complementary tandem
      sequence E1-X-E2 at the target. It is shown that association constants
      characterizing the affinity of the reagent X to the effector containing complexes
      PE1, PE2 and PE1E2 may be calculated from the dependencies of [PZ] infinity on
      the initial concentration chi 0 of X providing the sufficient excess of effectors
      is present. The approach was applied to reaction of C1RCH2NHpd(TTCCCA) with 26
      mer dTTGCCTTGAATGGGAAGAGGGTCATT and effectors Phn-L-pd(TTCAAGG-C)p-L-Phn(E1) and
      Phn-L-pd(TGACCCTC)p-L-Phn(E2) where Phn- is N-(2-hydroxyethyl)-phenazinium
      residue and L is -NHCH2CH2NH- spacer. The association constants were found to be
      Kxe1 = 6.75 x 10(5)M-1, Kxe2 = 4.15 x 10(4)M-1 and Kxe12 = 5.87 x 10(6)M-1 as
      compared with the affinity of X to P Kx = 2.16 x 10(4)M-1 in the absence of
      effectors. The experiments on self-alkylation of target reactive derivative
      C1RCH2NHpd(TTGCCTTGAATGGGAAGAGGGTCATT) both in the presence and in the absence of
      effector E2 as well as the Molecular Mechanics calculations of its prereactive
      states showed target to form the hairpin secondary structure. Under reasonable
      suggestions taking into account the internal structure of the target co
      operativity parameters describing the contribution of interactions of the
      terminal nucleotides of X with adjacent residues of effector were calculated and
      found to be alpha 1 = 16, alpha 2 = 10 and alpha 12 = 139 for the duplexes PXE1,
      PXE2 and PXE1E2, respectively.

PMID- 8527027
TI  - Stabilization of parallel (recombinant) triplex with propidium iodide.
AB  - Earlier we have shown that the oligonucleotide 5'-d(CATGCTAACT)-L-d(AGTTAGCATG)-L
      d(CATGCTAACT)-3' [L = pO(CH2CH2O)3p] is able to fold back forming intramolecular
      RecA-independent triplex with identical strands oriented parallel to each other
      (parallel triplex) [A.K. Shchyolkina, E.N. Timofeev, O.F. Borisova, I.A.
      Il'icheva, E.E. Minyat, E.V. Khomyakova, V.L. Florentiev, FEBS Letters 339, 113
      118 (1994) (1)]. In this study the propidium iodide (PI) was found to intercalate
      into the parallel triplex and increase its stability significantly (Tm increased
      from 21.4 up to 44.4 degrees C in 0.01 M Na phosphate buffer, pH 7, 0.1 M NaCl,
      when three PI molecules per triplex were bound). Fluorescence excitation and
      emission spectra, the quantum yield of fluorescence (q = 0.16) and the
      fluorescence lifetime of PI (tau = 24.5 ns at 3 degrees C) for the parallel
      triplex studied were shown to be similar to those for DNA. Scatchard binding
      plots indicated an anticooperative mode of PI binding to the parallel triplex.
      The association constant is close to that of PI binding to DNA. The fluorescence
      experiments revealed the maximum number of binding sites to be five PI molecules
      per one triplex molecule. Molecular mechanics calculation of possible structures
      for the parallel triplex-PI complex were performed.

PMID- 8527028
TI  - The first solvation shell of magnesium and calcium ions in a model nucleic acid
      environment: an ab initio study.
AB  - The interaction of organophosphate anions with divalent metal ions is central to
      many biological catalytic events. While experimental structural studies can give
      insight into the likely geometries that can be adopted, quantum mechanics allows
      for a more complete exploration of the competing forms. Ab initio quantum
      mechanical calculations have been performed on a series of complexes comprised of
      dimethyl phosphate, a divalent metal ion (either Mg(II) or Ca(II)) and water of
      hydration. An additional series of complexes were studied that included a Cl(I)
      ion to provide for charge neutrality. The most stable orientation of the hydrated
      metal ion complexed with the phosphate anion occurs when the metal ion is in a
      unidentate, rather than bidentate, orientation. The question of whether the
      divalent metal ion is located in the phosphinyl (-PO2(-)-) plane depends on the
      identity of the divalent metal ion and on the charge state of the complex.

PMID- 8527029
TI  - Intramolecular TAT triplex in (dA)58.(dT)58. influence of ions.
AB  - Supercoil-stabilized intramolecular triplexes have been described under various
      conditions in different polypurine.polypyrimidine sequences such as (dG)n.(dC)n
      and mixed sequences including d(GA)n.d(CT)n while information about the triplexes
      in (dA)n.(dT)n is scarce. Using osmium tetroxide complexes and diethyl
      pyrocarbonate as structural probes, we show a pyrimidine.purine.pyrimidine (TAT)
      triplex in (dA)58.(dT)58 sequence in a supercoiled plasmid pE19. Strong
      modification of approximately six central thymines and approximately six T's at
      the 3'-end of the (dT)58 stretch as well as the DEPC modification of the 5'-half
      of the (dA)58 strand suggested the prevalence of the H-y3 triplex conformer. At
      native superhelix density, optimum conditions for the triplex formation were
      close to 1 mM MgCl2, pH 8.5. At room temperature and MgCl2 concentrations below
      0.5 and above 5 mM, almost no triplex was formed. It is suggested that the
      absence of the triplex at higher MgCl2 concentrations is due to the stabilization
      of the duplex by Mg2+ ions which prevents the duplex opening necessary for the
      triplex formation. At higher temperatures, favorable for duplex opening (e.g. 55
      degrees C), the TAT triplex is formed even in the presence of 10 mM MgCl2. Among
      Ca2+, Sr2+, Ba2+, Cd2+, Zn2+ and Ni2+, only Ca2+ and Sr2+ yielded a modification
      pattern similar to that obtained with Mg2+; the modification pattern produced in
      the presence of Sr2+ was, however, much less intense. In the presence of 1 mM
      MgCl2, a decrease in pH from 8.5 to 7.7 resulted in a strong decrease of the
      triplex content. At highly negative superhelix density, the conditions for
      triplex formation were less stringent, and the triplex was observed even in the
      absence of MgCl2.

PMID- 8527030
TI  - The size of the topological domain modulates the B-Z transition of a (TG)n
      containing repeat.
AB  - Under negative superhelical stress, long (TG)n containing repeats experience a
      stepwise multiple B-Z transitions. We have investigated the effect of the plasmid
      size on this transitional behavior. A 66-bp (TG)n containing repeat from the 5'
      untranscribed region of mouse ribosomal DNA was inserted in a 3-kb, a 6.5-kb and
      a 12.5-kb plasmids and its supercoil-driven B-Z transition was followed by OsO4
      probing of topoisomer-populations. Our results show a clear correlation between
      the size of the topological domain and the extent of the region that converts
      cooperatively into Z-DNA at the initial transition.

PMID- 8527031
TI  - Structures of poly(dG-dC) and poly(dA-dT) stabilized by anions.
AB  - Infrared spectra were used to show that the sodium salts of acetate, sulfate and
      phosphate (pH 7.2) selectively stabilize some of the alternative structures of
      poly(dG-dC).Na and poly(dA-dT).Na as a function of hydration in nonoriented gels.
      NaCl was used as a reference. Each anion was present at 0.36 mole per mole of
      nucleotide residue. The weak absorption bands from these anions did not interfere
      with conclusive interpretation of the IR spectra of the polynucleotides. Poly(dG
      dC).Na assumed the usual B* structure with each of the anions at high hydrations
      (r.h. of the ambient air > or = 94%). Lowering the hydration gave the following
      results. With acetate, the B* structure remained with only a small fraction of a
      modified Z or some other unusual structure present. With sulfate or phosphate, a
      sharp transition to the Z structure occurred (essentially complete by 86% r.h.).
      With reference to chloride ions, acetate favors the B* while sulfate and
      phosphate (pH 7.2) favors the Z structure. Poly(dA-dT).Na assumed the usual B
      structure with each of the anions at high hydrations. Lowering the hydration gave
      the following results. With acetate, the A structure was observed at the same
      hydrations as with chloride. With sulfate, a sharper transition to the A
      structure occurred (complete by 80% r.h.). With phosphate, a still sharper
      transition to the A structure occurred (complete by 86% r.h.). With reference to
      chloride, acetate shows little difference but sulfate and phosphate (pH 7.2)
      promote the A over the B structure. These results are compared with past results
      for NaNO3.

PMID- 8527032
TI  - A comparative study of ATP and GTP complexation with trivalent Al, Ga and Fe
      cations. Determination of cation binding site and nucleotide conformation by FTIR
      difference spectroscopy.
AB  - The interactions of adenosine-5'-triphosphate (Na2H2ATP) and guanosine-5'
      triphosphate (Na2H2GTP) with trivalent Al, Ga and Fe cations are investigated in
      aqueous solution at pH = 6-7 with metal/nucleotide ratios (r) 1/10, 1/2, 1 and 4.
      Fourier Transform infrared (FTIR) difference spectroscopy is used to characterize
      the nature of metal cation binding and nucleotide conformational variations, in
      aqueous solution. Spectroscopic evidences show that at low cation concentration
      (r = 1/10), metal binding is mainly through the -PO2- and -PO3(2-) groups of the
      nucleotide moiety (outer-sphere), while at r > 1/10, in addition to direct metal
      phosphate binding (chelation), minor metal-base complexes are also formed via
      indirect metal-NH2 or metal-carbonyl interaction (through H2O). At r = 1, metal
      macrochelate formation occurs, involving direct cation coordination to phosphate
      groups and imidazol N-7 atom with an indirect metal-NH2 or metal-carbonyl
      interaction. At r = 4, polymerization of these metal complexes is observed
      through nucleotide phosphate chain. The amount of cation/phosphate binding is
      considerably larger than that of metal/base binding. Evidence for metal-phosphate
      coordination comes from major spectral changes (shifting and intensity
      variations) of the alpha-, beta- and gamma-PO2- vibrations in the region 1250-900
      cm-1, while metal-base binding is characterized by spectral alterations of the
      bands at 1700 (guanine carbonyl stretch), 1695 (adenine N-1-H+ mode), 1650-1660
      (NH2 bending), 1610-1613 (pyrimidine), 1575 (pyrimidine), 1535-1540 (imidazol),
      1470-1480 (imidazol) and 1377 cm-1 (imidazol). The ribose moiety shows C2'
      endo/anti conformation for the free ATP and its metal-ATP complexes with an
      infrared marked band at 821 cm-1. A mixture of both C2'-endo/anti and C3'
      endo/anti conformations are occurring for the free GTP and its trivalent metal
      complexes with marker bands at 820 and 800 cm-1.

PMID- 8527033
TI  - Osmotic effectors and DNA structure: effect of glycine on precipitation of DNA by
      multivalent cations.
AB  - We have investigated the effect of glycine (an organic osmolyte) on DNA
      precipitation induced by spermine4+, spermidine3+ and Tb3+ addition, using
      circular dichroism (CD), UV spectroscopy (UV), and electric linear dichroism
      (ELD) techniques. DNA precipitation by the three compounds is perturbed by
      glycine: more spermine4+, spermidine3+ and Tb3+ must be added to obtain the same
      extent of precipitation as compared to the behaviour in absence of this organic
      osmolyte. It seems that glycine has a general effect on the DNA environment.
      Calculations based on experimental results and Manning's counterion condensation
      theory show that glycine could modify the electrostatic environment of DNA as a
      consequence of a change in dielectric constant.

PMID- 8527034
TI  - Thalamostriatal projection neurons in birds utilize LANT6 and neurotensin: a
      light and electron microscopic double-labeling study.
AB  - Based on its location, connectivity and neurotransmitter content, the dorsal
      thalamic zone in birds appears to be homologous to the intralaminar, midline, and
      mediodorsal nuclear complex in the thalamus of mammals. We investigated the
      neuroactive substances used by thalamostriatal projection neurons of the dorsal
      thalamic zone in the pigeon. Single-labeling experiments showed that many neurons
      in the dorsal thalamic zone are immunoreactive for neurotensin and the
      neurotensin-related hexapeptide, (Lys8,Asn9)NT(8-13) (LANT6). Double-labeling
      experiments, using the retrograde fluorescent tracer, FluoroGold, combined with
      fluorescence immunocytochemistry for either LANT6 or neurotensin, showed that
      neurotensin- and LANT6-containing neurons in the dorsal thalamic zone project to
      the striatum of the basal ganglia. Immunofluorescence double-labeling experiments
      showed that neurotensin and LANT6 are often (possibly always) co-expressed in
      neurons in the dorsal thalamic zone. Electron microscopic immunohistochemical
      double-labeling showed that LANT6 terminals in the striatum make asymmetric
      contacts with heads of spines labeled for substance P and heads of spines not
      labeled for substance P, suggesting that these terminals synapse with both
      substance P-containing and non-substance P-containing medium spiny striatal
      projection neurons. These findings indicate that LANT6 and neurotensin may be
      utilized as neurotransmitters in thalamostriatal projections in birds and raise
      the possibility that this may also be the case in other amniotes.

PMID- 8527035
TI  - Identified cholinergic neurones in the adult rat brain are enriched in GAP-43
      mRNA: a double in situ hybridisation study.
AB  - The cellular expression of growth associated protein-43 mRNA by identified
      choline acetyl transferase mRNA positive cells was investigated in the mature rat
      brain using a combined radioactive and non-radioactive in situ hybridisation
      technique. Cellular sites of growth associated protein-43 mRNA were detected
      using a 35S-oligonucleotide while choline acetyl transferase mRNA positive
      neurones were identified using two alkaline phosphatase-labelled probes. In the
      cholinergic cells of the corpus striatum, basal forebrain and laterodorsal
      tegmental nucleus a specific growth associated protein-43 hybridisation signal
      (silver grains) was detected, demonstrating that these choline acetyl transferase
      mRNA positive cells are enriched in growth associated protein-43 gene
      transcripts. By contrast, the large cholinergic cells of the motor nucleus of the
      trigeminal nerve did not express growth associated protein-43 mRNA.
      Quantification of the growth associated protein-43 hybridisation signal expressed
      by identified choline acetyl transferase mRNA positive cells showed regional
      variations in the relative cellular abundance of this transcript; cholinergic
      cells in the laterodorsal tegmental nucleus and corpus striatum expressed the
      strongest cellular hybridisation signal. Mean cross-sectional somatic area
      measurements of these growth associated protein-43/cholinergic positive cells
      confirmed the identity of these neurones as belonging to the cholinergic
      phenotype. A strong 35S-growth associated protein-43 hybridisation signal was
      detected also in numerous other non-choline acetyl transferase mRNA positive
      nerve cells in other regions of the brain, although the chemical phenotypes of
      these neurones were not determined. Our data reveal that expression of the growth
      associated protein GAP-43 is maintained in identified cholinergic neurones in the
      postnatal rat brain, suggesting that this protein may subserve important
      functions in cholinergic and other neurones of the adult mammalian brain.

PMID- 8527036
TI  - Ontogeny of vasotocinergic and mesotocinergic systems in the brain of the South
      African clawed frog Xenopus laevis.
AB  - For a better understanding of the development of neurotransmitter systems and of
      their putative functional significance during ontogenesis, the development of the
      vasotocin (AVT) and mesotocin (MST) systems in the brain of Xenopus laevis was
      studied by means of immunohistochemical techniques. Weakly immunoreactive fibers
      were already present at late embryonic stage 38 in the caudoventral part of the
      telencephalon and in the ventral part of the diencephalon. The earliest
      immunodetectable AVT and MST immunoreactive cell bodies were found in the
      developing preoptic area at late embryonic stage 43. At the end of the embryonic
      period (stage 45), AVT immunoreactive fibers have reached the future medial
      amygdala, the midbrain tegmentum, the median eminence and the neural lobe of the
      pituitary. When compared with AVT immunoreactive fibers, the development of MST
      fibers shows some temporal delay. During the premetamorphosis (stages 45-52), AVT
      immunoreactive cell bodies appear in the medial part of the suprachiasmatic
      nucleus, the dorsal infundibular region, and the midbrain tegmentum, whereas
      fibers can now be traced to the nucleus accumbens, the septum and the medial
      amygdala in the forebrain, to the midbrain tegmentum, the reticular formation,
      the raphe nuclei, and the solitary tract nucleus in the brainstem, and to the
      spinal cord. Further maturation of the AVT system during prometamorphosis (stages
      53-58) includes the appearance of immunoreactive cell bodies in the lateral part
      of the suprachiasmatic nucleus, the ventral preoptic area, and the dorsal
      infundibular region. By the end of the metamorphosis (stage 65), the maturation
      of the AVT/MST systems reaches an almost adult-like pattern. It should be noted
      that in amphibians, in contrast to mammals, the early appearance of the AVT/MST
      systems, including their extensive extrahypothalamic component, suggests that the
      two neuropeptidergic systems may play a significant role during development.

PMID- 8527037
TI  - Time dependent changes in DA uptake sites, D1 and D2 receptor binding and mRNA
      after 6-OHDA lesions of the medial forebrain bundle in the rat brain.
AB  - Quantitative receptor autoradiography and in situ hybridization techniques were
      used to examine the temporal pattern of changes in dopamine uptake sites, D1 and
      D2 receptors and their transcripts in the striata of animals lesioned with 6
      hydroxydopamine. Animals were unilaterally lesioned in the medial forebrain
      bundle and the brains were analyzed at 1, 2, 4, 6, 8, and 16 weeks postlesion.
      Degeneration of the nigrostriatal pathway induced a significant loss of dopamine
      uptake sites in the ipsilateral caudate putamen of all lesioned animals. D1
      receptor binding was significantly increased in the caudate putamen on the
      lesioned side from 1 week to 16 weeks postlesion, whereas the expression of D1
      receptor mRNA did not show any change during this period. There was a significant
      upregulation of D2 receptor binding as well as D2 mRNA from 2 weeks to 8 weeks
      postlesion. However, at 16 weeks postlesion, D2 receptor binding continued to
      increase, whereas the mRNA appeared to compensate. These studies show that a
      different regulatory mechanism may exist between these two DA receptor subtypes.
      D1 receptor changes occur at the post-transcriptional or translational level,
      whereas D2 alterations occur by both transcriptional and translational processes.
      These studies also indicate that the postsynaptic supersensitivity observed in D1
      receptors may not be accompanied by a corresponding increase in D1 receptor mRNA.

PMID- 8527038
TI  - Secretoneurin-immunoreactivity in nerve terminals apposing identified
      preganglionic sympathetic neurons in the rat: colocalization with substance P and
      enkephalin.
AB  - Preganglionic sympathetic neurons projecting to the superior cervical ganglion
      are innervated by nerve fibers containing classical neurotransmitters as well as
      neuropeptides. In this study we examined the possible participation of a novel
      peptide, secretoneurin (a cleavage product of secretogranin II), in regulation of
      sympathetic outflow to head and neck by using a retrograde labelling-technique
      combined with immunohistochemistry. In addition, the coexistence of secretoneurin
      with substance P and leu-enkephalin, peptides known to innervate preganglionic
      neurons, was investigated. The majority of retrogradely labeled neurons were
      localized in the nucleus intermediolateralis of spinal cord segments T1-T3
      (maximum at T2). Nearly all of Fast Blue positive neuronal perikarya were apposed
      by nerve fibers and terminals exhibiting immunoreactivity to secretoneurin. The
      main secretoneurin-immunoreactive form found in the upper thoracic segments
      corresponded to the free peptide secretoneurin as revealed by chromatography and
      radioimmunoassay. More than half of labeled neurons were surrounded by nerve
      endings containing in addition substance P or leu-enkephalin which were also,
      however, less frequently colocalized. Our results suggest that secretoneurin
      influences the activity of preganglionic sympathetic neurons projecting to the
      superior cervical ganglion. Regarding their frequent colocalization with
      substance P and leu-enkephalin, functional interactions of these peptides on
      preganglionic sympathetic nerve activity have to be considered.

PMID- 8527039
TI  - Ultrastructural study of substance P receptors in the dorsal horn of the rat
      spinal cord using monoclonal anti-complementary peptide antibody.
AB  - A monoclonal antibody directed against a peptide (PS5) specified by RNA
      complementary to the mRNA coding for substance P (SP), was used to label SP
      receptors in the rat spinal cord as demonstrated by light and electron
      microscopy. An immunocytochemical method (avidin-biotin-peroxidase) was used on
      vibratome sections from rats perfused with paraformaldehyde. Immunoreactivity was
      observed principally in the two superficial layers of the dorsal horn, in lamina
      X and the region of motoneurons. The labeling was absent when the antibody was
      preincubated with the complementary peptide (PS5) used as immunogen. Competition
      between the anti-complementary peptide antibody and different ligands was tested
      by preincubation of tissue sections with the ligand in the presence of peptidase
      inhibitors before addition of the antibody. A specific agonist (SP) or antagonist
      (spantide, RP 67580) at 10(-6)M led to total absence of labeling. These results
      indicate that under our experimental conditions, the anti-complementary peptide
      antibody recognizes a SP binding site in the rat spinal cord. Electron
      microscopic study of the two superficial laminae of the dorsal horn showed that
      immunolabeling was mainly localized extracellularly at apposing neuronal plasma
      membranes. It was mostly associated with axodendritic or axosomatic appositions.
      Occasionally labeling was observed between two axon terminals. In all cases,
      these appositions were non-junctional. Generally, neuronal processes involved in
      these appositions did not contain large granular vesicles. These observations
      suggest that SP may act in a diffuse, nonsynaptic manner probably on targets
      distant from SP release sites.

PMID- 8527040
TI  - Effect of growth factors on the expression of proto-oncogenes c-fos and c-myc in
      FRTL-5 cell line.
AB  - This study was performed to prove the hypothesis that oncogene expressions would
      have the same patterns with those of cellular growth to growth factors in FRTL-5
      cells. Ribonucleic acids of FRTL-5 were extracted at 15', 30', 60' and 120' after
      administration of growth factors to quiescent FRTL-5, and blotted to the
      nitrocellulose membrane. They were hybridized with radiolabelled c-fos, c-myc and
      beta-actin probes. Hybridized dot blots were autoradiographed and the amount of
      radioactivity was measured by densitometry. Densitometric readings were used as
      the indices of oncogene expressions. Expressions of c-fos and c-myc were more
      prominent in combined administrations of TSH (10 mU/ml) and IGF-I (100 ng/ml) or
      IgG of Graves' disease (Graves' IgG; 1 mg/ml) and IGF-I than in combined
      administration of TSH and Graves' IgG. IgG of primary myxedema suppressed
      oncogene expressions by TSH or Graves' IgG, but not by IGF-I. From the above
      results, it was suggested that expressions of c-fos and c-myc to growth factors
      would have similar patterns with those of cell growth to growth factors in FRTL
      5, and the actions of TSH and Graves' IgG would be manifested through same signal
      transduction system, but IGF-I would be manifested by its own.

PMID- 8527041
TI  - Peripheral blood lymphocyte subsets in patients with stomach cancer.
AB  - The present study was conducted in order to investigate the immunologic
      alterations alongside the numerical changes in peripheral blood lymphocytes(PBL)
      and their subsets in stomach cancer patients. Lymphocyte surface markers were
      determined in 85 stomach cancer patients and 49 controls by indirect
      immunofluorescence technique using monoclonal antibodies. Monoclonal antibodies
      used were Leu 2a(CD8, suppressor/cytotoxic T cells), Leu 3a(CD4, inducer/helper T
      cells), Leu 4(CD3, pan T reagent), Leu 11(CD16, natural killer cells) and Leu
      12(CD19, B cells). The numbers of PBL, CD3+, CD4+, CD8+, CD16+ and CD19+ cells
      significantly decreased and the CD4: CD8 value increased in 85 patients with
      stomach cancer compared to those in controls(p < 0.01). In stage I(n = 17),
      neither PBL, their subsets nor the CD4: CD8 value were significantly different
      from those of the controls. In stage II(n = 17), the numbers of PBL, CD3+, CD4+
      and CD8+ cells decreased(p < 0.01). In stage III(n = 24) and IV(n = 27), PBL and
      all subsets measured decreased(p < 0.01). The CD4: CD8 value showed significant
      increases in stages III and IV(p < 0.01), because the CD8+ cells decreased to a
      greater extent than did the CD4+ cells. The results demonstrating that the
      lymphocyte subsets are depressed differentially with the stage suggest that host
      immunity is impaired with the progression of stomach cancer.

PMID- 8527042
TI  - Identification of CD44 splice variant in Korean colorectal cancers and cell
      lines.
AB  - CD44 is a glycoprotein expressed in a wide variety of cell types. Recently
      expression of some alternatively-spliced variants of CD44 transcripts (CD44v) has
      been suggested to play a potential role in tumor metastasis and the detection of
      CD44v containing exon 6 to 11 may be helpful for the diagnosis of cancers.
      Expressions of CD44v containing exon 6 to 11 were investigated in 20 human
      colorectal cancer samples, peripheral blood leukocytes isolated from colorectal
      cancer patients, and 4 colorectal cancer cell lines using reverse transcription
      polymerase chain reaction and Southern blot analysis. The standard form of CD44
      transcripts was expressed in all samples tested. CD44v containing exon 6 to 11
      was expressed in 18 cases of colorectal cancers (sensitivity = 90%), 3 out of 4
      cell lines, and one normal tissue (specificity = 95%). These results suggest that
      the expression of CD44v containing exon 6 to 11 can be regarded as tumor specific
      and that this marker may be helpful for the early diagnosis of colon cancers, if
      specimens from the early stage are available.

PMID- 8527043
TI  - An immunohistochemical study of the expression of p53 protein in colon cancer.
AB  - A total of 471 cases of colonic adenocarcinomas and 28 cases of colonic adenomas
      were examined immunohistochemically to evaluate the expression of p53 protein in
      the light of their relationship with various prognostic factors. A monoclonal
      antibody, p53 DO-7, was used in the study. Two hundred and fourteen
      adenocarcinomas (45.5%) showed positive staining for p53, however only three of
      the adenomas (10.3%) were positive (P < 0.05). p53 was stained to neoplastic
      nuclei. Adjacent normal mucosal cells were negative. There were no significant
      correlations between p53 expression and prognostic parameters such as age, sex,
      gross configuration, modified Astler-Coller stages, microscopic tumor growth
      patterns, tumor depth, tumor size and lymph node involvements. However, left
      sided adenocarcinomas (49.3%) expressed p53 more often than right sided
      adenocarcinomas (35.6%) (P = 0.01). The positive rates were different according
      to the histologic differentiation; 45.2% in well differentiated, 51.3% in
      moderately well differentiated, 23.8% in poorly differentiated, and 26.5% in
      mucinous carcinomas (P = 0.011). The mean survival periods of the p53 positive
      and negative groups were 29 months and 32 months, respectively (P = 0.385).
      However, overall survival for patients with grade one and two positive p53 was
      better than those of grade three and four positive cases (P = 0.028). In
      conclusion, the result of this multivariate analysis suggests that
      immunohistochemically strong p53 protein expression (more than 30% of tumor
      cells) has value in estimating a prognosis for patients with colorectal
      adenocarcinomas.

PMID- 8527044
TI  - Transferrin receptor expression of the hyperplastic lesions of hepatocyte in
      experimental hepatocarcinogenesis.
AB  - Transferrin receptor (TR) performs the major function of binding and
      internalizing its specific iron-loaded ligand, transferrin, and its expression is
      closely linked to the proliferation status of the cell. This study was undertaken
      to elucidate TR expression in the hyperplastic lesion of hepatocyte in chemically
      induced hepatic carcinogenesis. The resistant hepatocyte model was chosen for a
      rat model of carcinogenesis and Sprague-Dawley rats were divided into the
      following groups: the control groups of normal diet and iron-rich diet with or
      without hydroxyquinoline and the groups of carcinogen alone and carcinogen plus
      iron-rich diet with or without administration of hydroxyquinoline. Microscopic
      changes in the liver, expression of transferrin receptor and glucose-6
      phosphatase were studied. The hepatocyte of the control group showed both
      cytoplasmic and membranous expression of TR. The liver of rats fed on high iron
      diet accumulated iron and the expression of TR was down regulated by intrahepatic
      iron accumulation. In the carcinogen administered group the resistant hepatocyte
      of hyperplastic lesion revealed strong membranous expression of TR and failed to
      accumulate iron in spite of high iron diet but in contrast the surrounding non
      resistant hepatocyte expressed TR in both the membrane and cytoplasm and stored
      iron when fed on high iron diet. The strong membranous expression of TR is one of
      the characteristics of the resistant hepatocyte of hyperplastic lesion and it
      seems to be related to the inability to accumulate iron in spite of a high iron
      diet.

PMID- 8527045
TI  - Sequential changes of traumatic vertebral compression fracture on MR imaging.
AB  - The purpose of this study was to evaluate the sequential signal intensity changes
      in post-traumatic vertebral compression fractures of varying ages. Sixty-six
      patients with 115 post-traumatic vertebral compression fractures underwent MR
      imaging. The ages of fractures at the time of MR images ranged from 1 day to 6
      years. Sequential follow-up MR imagings were obtained in 4 patients for 2 years
      after initial MR examination. The fracture sites in all 52 fractures with
      traumatic events less than 3 months prior were hypointense on T1-weighted images
      and hyperintense on T2-weighted images (type I). A type I fracture could be
      subdivided into 3 patterns depending on its morphologic appearance: diffuse (type
      Ia); patchy (type Ib); and bandlike (type Ic). In 12 fractures of 3 to 5 months
      after trauma, six showed focal hypointensity (type II) in all pulse sequences,
      and six showed isointensity (type IV). Four of 51 fractures with trauma over 5
      months showed focal hyperintensity on T1-weighted images and isointensity on T2
      weighted images (type III); and the remaining 47 fractures showed isointensity on
      all sequences (type IV). In conclusion, MR imaging is useful in predicting the
      age of known traumatic compression fractures, so familiarity with these
      sequential MR findings would be helpful in distinguishing benign from malignant
      fractures.

PMID- 8527046
TI  - The relationships of motor function, education, age and cognitive function to the
      physical activities of daily living.
AB  - The physical activities of daily living are a final outcome of many functions and
      dependent on many factors. This study was aimed at exploring the relationships of
      motor function, dementia, education, age, and cognitive function to the physical
      activities of daily living in 67 elderly people residing in an institution in
      Taegu, Korea. Their mean ( +/- SD) age was 75.6 +/- 8.1 and 24 (35.8%) were men.
      Twenty-eight (41.8%) were classified as having definite cognitive impairment, 17
      (25.4%) as having questionable impairment, and 22 (32.8%) as having no impairment
      by the Korean version of the mini-mental state examination. Of the aforementioned
      5 variables, the Motoricity Index could account for 42% of the Barthel Activities
      of Daily Living variance. If the modified Blessed Dementia Rating Scale was
      included in the multiple regression, the accountable portion of the Activities
      variance increased by 4% only. Using the 2 variables, regression equation, y =
      0.248 x chi 1-0.359 x chi 2-6.250 (y: Barthel Activities of Daily Living score,
      chi 1: Motoricity Index score, chi 2: modified Blessed Dementia Rating Scale
      score) could be produced. Conclusively, the physical activities of daily living
      of elderly people could be related mainly with motor function of the limbs and
      severity of dementia.

PMID- 8527047
TI  - Cobalt-induced occupational asthma associated with systemic illness.
AB  - We report a case of occupational asthma caused by cobalt associated with systemic
      symptoms. He was a non-atopic, ex-smoker and had worked in a glassware factory
      for 14 months. A skin prick test with CoSO4 up to 100 mg/ml showed a negative
      result. A bronchoprovocation test with CoSO4 demonstrated an isolated asthmatic
      response with systemic symptoms such as fever, arthralgia and myalgia. Although
      an initial methacholine bronchial challenge test showed a negative result, the
      following methacholine bronchial challenge test which was done 24 hours after the
      challenge testing demonstrated an increased airway hyperresponsiveness at 2.5
      mg/ml which recovered 7 days later. An intradermal skin test with 10 mg/ml and
      100 mg/ml CoSO4 solution demonstrated positive responses respectively(13 x 12/40
      x 32, 20 x 15/40 x 37 <mm>, histamine 16 x 14/64 x 50). A patch test including
      cobalt showed a negative result. Bronchoalveolar lavage fluid after the cobalt
      inhalation testing and other laboratory findings showed no evidence of
      hypersensitivity pneumonitis. These results suggested that cobalt could induce
      occupational asthma with systemic illness in an exposed worker.

PMID- 8527048
TI  - The first documentation of Li-Fraumeni syndrome in Korea.
AB  - Li-Fraumeni syndrome(LFS) is an autosomal dominant disorder that predisposes
      individuals to multiple forms of cancer including breast cancer, soft tissue
      sarcoma, brain tumor, osteosarcoma, leukemia, and adrenocortical carcinoma.
      Recently, germ-line mutation of the p53 tumor suppressor gene has been implicated
      in this familial disorder. We report a case of a 25-year old woman who presented
      with bilateral breast cancer and uterine leiomyoma. Her mother had died of early
      onset bilateral breast cancer. And her younger sister had breast carcinoma as
      well, which was identified at the age of 22, indicating her strong familial
      history. To test for the presence of the p53 germ-line mutation, we analyzed the
      genomic DNA from the peripheral blood of the proband and her sister by PCR-SSCP
      analysis of exon 5 through exon 8 of the p53 gene. As a result, a p53 mutation in
      exon 7 was detected in an allele, and it was shared with her sister as the same
      pattern. Sequencing analysis determined the altered nucleotide at codon 248(CGG >
      TGG) which is one of the most frequent mutation sites related to LFS. Therefore,
      this patient has the most consistent characteristic features of LFS phenotype and
      it is believed that this case is the first report of a family with Li-Fraumeni
      syndrome carrying the p53 germ-line mutation in Korea.

PMID- 8527049
TI  - Spindle cell hemangioendothelioma--a case report.
AB  - Spindle cell hemangioendothelioma is a rare vascular tumor which is presented
      with subcutaneous nodules and follows a benign indolent course but has a
      recurrent tendency, and is histologically resembling a cavernous hemangioma and
      Kaposi's sarcoma. We present a case of spindle cell hemangioendothelioma
      possessing clinical aggressiveness with painful bony erosion, histologic
      pleomorphism and mitoses. A 20-year-old man presented with a recurrent painful
      mass on the left ankle. The mass was dark brown and firm with irregular margins
      and measured 1.5 cm in diameter, which affected and eroded the underlying medial
      malleolus of the left tibia. Microscopically, the tumor was composed of cavernous
      endothelial-lined blood spaces and spindle cellular areas mimicking Kaposi's
      sarcoma. The spindle cells intermingled with plump epithelioid cells and showed a
      moderate degree of pleomorphism with occasional mitoses. Immunohistochemically,
      the spindle cells were focally positive for factor VIII-associated antigen and
      vimentin, and negative for S-100 protein, desmin, and epithelial membrane
      antigen.

PMID- 8527050
TI  - Eosinophilic gastroenteritis associated with food allergy and bronchial asthma.
AB  - In some patients, eosinophilic gastroenteritis(EG) occurs in those with food
      allergy. We experienced a non-atopic asthmatic who had an EG associated with food
      allergy to fish and eggs, and blood eosinophilia. A skin prick test and RAST to
      causative food allergens showed a negative result. A fiber-optic endoscopic
      biopsy from the gastric mucosa showed an intense eosinophilic infiltration. We
      could find symptomatic improvement and a disappearance of eosinophilic
      infiltration in gastric mucosa after complete avoidance from the causative food
      and oral cortcosteroid. It was suggested that fiber-optic endoscopic biopsy might
      be needed to identify coexisting EG if an allergic patient with blood
      eosinophilia complains of severe gastrointestinal symptoms.

PMID- 8527051
TI  - A case of abdominal cocoon.
AB  - Abdominal cocoon is a rare disease of the peritoneum and almost invariably
      presents as an acute or subacute intestinal obstruction with or without a mass.
      The etiology of this disease is largely unknown and abdominal cocoon of unknown
      etiology has been limited to the tropical and subtropical zones and primarily
      affects young adolescent females. In the temperate zone, only one case has been
      reported from the United Kingdom, but the patient was also born in Pakistan. No
      case of abdominal cocoon purely developed in the temperate zone has been
      reported. Recently, we experienced a case of abdominal cocoon in a 34-year-old
      female patient(Korean) who had never been abroad. The diagnosis was made
      postoperatively by reviewing the literature. We herein report this rare condition
      developed in an unusual geographical location with a brief review of the
      literature.

PMID- 8527052
TI  - Unique and interactive effects of depression, age, socioeconomic advantage, and
      gender on cognitive performance of normal healthy older people.
AB  - A sample of 4,243 residents of Manchester, England and Newcastle-upon-Tyne,
      England, aged 50 to 93 years, completed the Beck Depression Scale (A.T. Beck,
      C.H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) and a battery of 6
      different cognitive tests. Beck scores were low, indicating gradations of
      dysphoria rather than clinical depression. Beck scores did not vary with age but
      were significantly higher for women than for men and for disadvantaged than for
      advantaged socioeconomic groups. Measures of fluid, but not of crystallized,
      ability declined as age increased. Socioeconomic disadvantage was associated with
      poorer performance on all cognitive tests. Men scored higher on a test of spatial
      reasoning, and women scored higher on a test of word definition and on 2 tests of
      verbal memory and learning. However, after variance associated with all these
      demographic and individual-difference variables was considered, and within a
      range indicative of dysphoria rather than clinical depression, higher Beck scores
      were associated with significantly poorer performance on both crystallized and
      fluid measures of cognitive ability. This association was less marked in women
      than in men, but age, socioeconomic advantage, and estimated lifetime
      intellectual ability did not act as protective or risk factors for vulnerability
      of cognitive processes to dysphoria.

PMID- 8527053
TI  - Age effects in cued recall: sources from implicit and explicit memory.
AB  - In 2 experiments, young and old adults were compared on cued recall using direct
      and indirect test instructions. Participants studied words under an incidental
      orienting task of rating each word for concreteness. Test cues were meaningfully
      related to the targets, and participants used them either to recall the studied
      word (direct test) or to generate a related word (indirect test). Target words
      and test cues varied in the number of associates linked to them prior to the
      laboratory experience, and effects of the size of the sets of associates were
      used as indicators of implicit memory search. Age differences were observed in
      the effects of target and cue set size as well as in the effects of type of test
      instruction.

PMID- 8527054
TI  - Aging and experience in the recognition of musical transpositions.
AB  - The authors examined the effects of age, musical experience, and characteristics
      of musical stimuli on a melodic short-term memory task in which participants had
      to recognize whether a tune was an exact transposition of another tune recently
      presented. Participants were musicians and nonmusicians between ages 18 and 30 or
      60 and 80. In 4 experiments, the authors found that age and experience affected
      different aspects of the task, with experience becoming more influential when
      interference was provided during the task. Age and experience interacted only
      weakly, and neither age nor experience influenced the superiority of tonal over
      atonal materials. Recognition memory for the sequences did not reflect the same
      pattern of results as the transposition task. The implications of these results
      for theories of aging, experience, and music cognition are discussed.

PMID- 8527055
TI  - Binding ties: closeness and conflict in adult children's caregiving
      relationships.
AB  - The authors used a path model to test the hypothesis that emotional closeness and
      conflict between adult-child caregivers (N = 90) and their impaired parents
      mediated the impact of the parents' functional and cognitive impairment on the
      caregivers' subjective stress, subjective effectiveness, and depression.
      Closeness mediated the relationship between cognitive impairment and both stress
      and effectiveness, whereas conflict mediated cognitive impairment for all 3
      outcomes and generally accounted for more variance. There was limited evidence
      that functional impairment was mediated by the quality of the relationship.
      Results highlight the importance of both positive and negative ties as
      intervening mechanisms influencing caregivers' well-being, especially in the
      presence of cognitive dysfunction.

PMID- 8527056
TI  - Perceptions of life stress and chronic insomnia in older adults.
AB  - This study compared the level of self-reported stress of 42 older good sleepers
      (M age = 68.2 years) and 42 poor sleepers (M age = 68.7 years). The relations
      among subjective ratings of sleep, level of perceived stress, and negative mood
      were analyzed for each group. Good and poor sleepers reported similar amounts of
      life stress, but the relations between life stress and sleep perceptions differed
      for the 2 groups. Specifically, within the group of poor sleepers, those with
      higher life stress had greater difficulty falling asleep and less early morning
      waking than did poor sleepers with lower life stress. There was no association
      between life stress and any sleep measures for good sleepers. These results are
      compatible with the notion that good and poor sleepers may have different
      susceptibilities to poor sleep despite experiencing similar stressful life
      events.

PMID- 8527057
TI  - Recurrent syndromal depression in caregivers.
AB  - The authors investigated recurrent syndromal depression in 103 caregivers using a
      structured clinical interview. Participants who cared for a family member with a
      progressive dementia were assessed annually for 3 years and divided into 3
      groups: never depressed (47%), episodically depressed (33%), and chronically
      depressed (20%). Compared with the other 2 groups, the chronically depressed
      caregivers reported greater levels of stress, upsetting social support,
      depressive symptomatology, along with higher frequencies of negative life events
      and more negative reactions to disruptive patient behavior. Precaregiving
      depression predicted depression during caregiving but did not sufficiently
      explain recurrent depression in caregivers. Lower levels of positive social
      support and higher number of life events were related to chronically elevated
      depressive symptoms and stress.

PMID- 8527058
TI  - Activity restriction mediates the association between pain and depressed affect:
      a study of younger and older adult cancer patients.
AB  - Associations are reported frequently among pain, functional disability, and
      symptoms of depression. The purpose of this longitudinal study was to further
      clarify relations among these variables. In 268 younger (ages 30-64) and older
      (ages 65-90) cancer outpatients, cross-sectional analyses replicated previous
      findings showing that effects of pain on symptoms of depression are mediated by
      functional disability. Longitudinal analyses revealed that as pain increased over
      time, so did activity restriction, which in turn predicted increases in depressed
      affect. Comparative analyses indicate that restriction of routine activities that
      are due to illness and pain may be more distressing to individuals less than 65
      years of age than to those 65 years of age or older. The results suggest that
      older persons are less distressed by restricted activities because of lower
      expectations about functional status and more experience with illness and
      disability.

PMID- 8527059
TI  - Implicit learning of a nonverbal sequence in younger and older adults.
AB  - Two experiments examined age-related differences in implicit serial learning
      using the M. J. Nissen and P. Bullemer (1987) task. Younger adults and 2 samples
      of older adults who differed in educational attainment, occupational status, and
      verbal ability were given a 10-trial repeating sequence embedded in 100-trial
      blocks. On each trial, participants pressed a key that matched a designated
      spatial location. Implicit learning was inferred from the difference in RT
      between a random sequence trial block and the immediately preceding block with
      the repeating sequence. Results indicated that negative transfer effects were
      comparable for the younger and higher ability older adults, but lower ability
      older adults showed less evidence of implicit learning. On an explicit task,
      younger and higher ability older adults were more accurate than the lower ability
      older adults. The implications of these findings for current views on implicit
      learning in adulthood are discussed.

PMID- 8527060
TI  - Individual differences in stimulus intensity modulation and its relationship to
      two styles of depression in older adults.
AB  - Research comparing depressive persons with and without manic symptoms shows
      striking parallels with differences between augmenters and reducers on the
      Kinesthetic Aftereffect (KAE) task (A. Petrie, 1967). Twenty-three community
      dwelling older adults identified by the Minnesota Multiphasic Personality
      Inventory (S. R. Hathaway & J. C. McKinley, 1951) as depressive without manic
      symptoms were compared with 24 older adults with manic symptoms on the KAE, the
      NEO Personality Inventory (NEO-PI; P. T. Costa & R. R. McCrae, 1985), and Strelau
      (J. Strelau, 1983) Temperament Inventory. As hypothesized, augmentation was
      related to depression without manic symptoms, and reduction was related to
      depression with manic symptoms. Stepwise discriminant analyses indicated that the
      KAE is a potent discriminator between the 2 types of depression. Three
      characteristics of Strelau's "strength of nervous system"--excitation, and
      inhibition and mobility--discriminate significantly between the 2 groups as well
      as NEO extraversion and conscientiousness. Results suggest that older depressive
      persons with and without manic symptoms may benefit from different therapeutic
      interventions.

PMID- 8527061
TI  - Representations of self across the life span.
AB  - This research extends a cognitive-developmental approach to examining age
      differences in self-representation from adolescence to mature adulthood and later
      life. The authors suggest that mature adults move from representations of self
      that are relatively poorly differentiated from others or social conventions to
      ones that involve emphasis on process, context, and individuality. Participants
      (n men = 73, n women = 76), ranging in age from 11 to 85 years, provided
      spontaneous accounts of their self-representations and responded to measures
      assessing cognitive and emotional functioning and broad dimensions of
      personality. On average, self-representation scores peaked in middle-aged adults
      and were lowest in the preadolescent and older adult age groups. Level of self
      representation was related to cognitive and personality variables, but there was
      some evidence that the pattern of correlates shifted from younger (ages 15-45) to
      older (ages 46-85) age segments.

PMID- 8527062
TI  - Larger nondeclarative than declarative deficits in learning and memory in human
      aging.
AB  - This study used classical conditioning as a measure of nondeclarative learning
      and compared it with verbal learning as a declarative measure. Eighty
      participants were tested using 1 of 2 paradigms (400-ms and 750-ms delay) for
      eyeblink classical conditioning (EBCC) and the California Verbal Learning Test
      (CVLT). Large age differences were observed in the nondeclarative EBCC task, even
      in the 750-ms paradigm, which is more optimal for older adults. Age differences
      in the nondeclarative EBCC task were larger in the 400-ms paradigm and equal in
      the 750-ms paradigm to the magnitude of age differences in the declarative CVLT
      task. Partial correlations (removing the variance that was due to age) showed no
      relation between performance on the nondeclarative and declarative tasks. The
      results contradict the common assumption that, in the same participants,
      nondeclarative learning and memory are more resistant to the effects of aging
      than are declarative learning and memory and suggest that nondeclarative learning
      and memory are not unitary.

PMID- 8527063
TI  - Aging, distraction, and the benefits of predictable location.
AB  - Three experiments examined the impact on reading time for younger and older
      adults in the absence vs. presence of distraction (marked by font type) in either
      fixed predictable locations (Experiments 1 and 2) or unpredictable locations
      (Experiment 3). Consistent with earlier work (S. L. Connelly, L. Hasher, & R. T.
      Zacks, 1991), older adults were markedly disrupted, relative to young adults,
      when distraction was present in unpredictable locations. When the location of
      distraction was fixed, however, the very large disadvantage that older adults
      otherwise experienced (slowed by as much as 46 s) diminished substantially (to as
      little as 2 s). Fixed location also eliminated the relatedness effect, by which
      older adults are especially susceptible to distraction from meaningfully related
      material.

PMID- 8527064
TI  - Genetic influences on memory performance in adulthood: comparison of Minnesota
      and Swedish twin data.
AB  - Results from 2 twin studies of aging differ concerning the heritability of memory
      performance in adulthood. Heritability estimates from the Minnesota Twin Study of
      Adult Development and Aging (MTSADA; D. Finkel & M. McGue, 1993) are larger than
      estimates from the Swedish data (N. L. Pedersen, R. Plomin, J. R. Nesselroade, &
      G. E. McClearn, 1992). Memory data were available from MTSADA on a sample of 112
      monozygotic (MZ) twin pairs and 111 dizygotic (DZ) twin pairs ages 27 to 88 years
      and from the Swedish study on a sample of 86 MZ and 110 DZ twin pairs who were
      reared together and were ages 27 to 85 years. Univariate and multivariate
      behavior genetic analyses were conducted to determine the significance and source
      of differences in heritability across studies. No significant age differences
      were found in either study. Study differences were found at the level of specific
      memory measures, but not at the level of a general memory factor.

PMID- 8527065
TI  - Role of family adaptability in the psychological adjustment of spouse caregivers
      to patients with dementia.
AB  - This study examined the role of family adaptability in moderating the impact of
      caregiving on psychological adjustment and the relationship between adaptability
      and marital roles for 54 spouse caregivers to patients with dementia. Greater
      memory and behavior problems were related to greater burden and depression. For
      caregivers who were lower in adaptability, longer hours of care were related to
      greater depression. For caregivers higher in adaptability, hours of care were
      unrelated to depression. Cluster analysis identified a subset of caregivers lower
      in adaptability, with a partner who was severely demented, who endorsed a spouse
      role. These caregivers were the most depressed in the sample. Implications for
      service providers and suggestions for future research are discussed.

PMID- 8527066
TI  - Cognitive mediation of adult age differences in language performance.
AB  - Young (M = 20 years) and old (M = 68 years) adults completed language processing
      tasks, measures of working memory capacity (backward span and the n-back lag
      task), inhibitory efficiency (Stroop interference), and processing speed (color
      naming). regression analyses revealed that each of the resource measures
      significantly predicted language performance and attenuated variance in language
      performance that would otherwise be attributed to age. When speed variance was
      entered into the equation first, the mediating influence of the inhibition and
      working memory measures remained significant. When speed and inhibition
      differences were controlled, the working memory measures could not reliably
      predict language performance. These results suggest that language performance
      differences may be fundamentally mediated by age differences in processing speed
      and inhibitory efficiency.

PMID- 8527067
TI  - Relationship of events and affect in the daily life of an elderly population.
AB  - The relationship between positive and negative events and emotional well-being
      for depressed and nondepressed residents of a nursing home and congregate housing
      care facility was examined. For 30 consecutive working days, each of 79
      participants was presented with the Philadelphia Geriatric Center Positive and
      Negative Affect rating scales. Events during the previous 24 hr were elicited by
      an open-ended format. Results indicated that variations in daily events (e.g.,
      health, family, self-initiated, and social events) were related to residents'
      affect, and there was congruence between mood and event valence when the effects
      of psychopathology and residence were removed. Thus, regardless of diagnosis or
      residential setting, people's moods showed a relationship to the quality of daily
      events. Findings also indicated that ratings of residents' affect could be
      translated into audits for institutional quality.

PMID- 8527068
TI  - Everyday problem solving in older adults: observational assessment and cognitive
      correlates.
AB  - Older adults' ability to solve practical problems in 3 domains of daily living
      was assessed using a new measure of everyday problem solving, the Observed Tasks
      of Daily Living (OTDL). Findings showed that the OTDL formed internally
      consistent scales representing 3 distinct factors of everyday problem solving.
      Moreover, the OTDL showed convergent validity with related scales of a paper-and
      pencil test. Older adults' performance on the OTDL was significantly correlated
      with their scores on measures of basic mental abilities. Path analysis showed
      that age affected older adults' performance on the OTDL directly and indirectly
      via cognitive abilities. Participants' education and health affected their
      everyday competence indirectly through cognitive abilities. The effects of
      perceptual speed and memory span were mediated by fluid and crystallized
      intelligence.

PMID- 8527069
TI  - Aging, source, and decision criteria: when false fame errors do and do not occur.
AB  - Two experiments investigated the influence of decision criteria on source memory
      performance of older adults and younger adults. Experiment 1 used the false fame
      paradigm, which encourages people to use relatively loose decision criteria when
      making what are, in essence, source judgments. Consistent with previous research,
      older adults made more false fame errors than younger adults. Experiment 2 was
      identical to Experiment 1 except that the fame judgments were made with the
      traditional source task format that encourages relatively stringent decision
      criteria when making source judgments: Possible sources were listed, and
      participants categorized names in terms of their source. In contrast to
      Experiment 1, older adults reduced their false fame errors to the level of
      younger adults. Encouraging older adults to use relatively stringent decision
      criteria when making source discriminations can reduce age differences in source
      misattributions.

PMID- 8527070
TI  - The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and
      the relative contributions of intra-uterine and intra-partum transmission.
AB  - OBJECTIVE: To derive reliable estimates of the sensitivity of HIV-1 DNA
      polymerase chain reaction (PCR) in the neonatal period and to quantify the
      relative contributions of intra-uterine and intra-partum transmission. METHODS:
      After reviewing studies on the early diagnosis of HIV-1 infection, investigators
      were asked to provide published and unpublished PCR test results on prospectively
      followed, non-breastfed, vertically infected children. Age-specific estimates of
      the sensitivity of PCR were derived using distribution-free methods for interval
      censored data. RESULTS: Data on 271 infected children were combined for analysis.
      PCR detected HIV-1 DNA in an estimated 38% [90% confidence interval (CI), 29-46]
      of HIV-infected children tested on the day of, or day after, birth. Sensitivity
      was observed to rise rapidly in the second week of life, reaching 93% (90% CI, 76
      97) by 14 days of age. CONCLUSION: The sensitivity of PCR in the neonatal period
      is higher than previously reported. This affects the clinical interpretation of
      an early negative test result and encourages the use of PCR as an endpoint for
      trials to evaluate interventions to reduce vertical transmission in non-breastfed
      populations. Approximately one-third of vertically acquired HIV-1 infection could
      be attributable to intra-uterine transmission.

PMID- 8527071
TI  - Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is
      associated with dementia.
AB  - OBJECTIVE: To relate the expression of HIV regulatory proteins and HIV-specific
      mRNA in the brain cells of infected individuals with clinical neurological
      disease. DESIGN: Formalin-fixed postmortem brain tissue from 14 HIV-infected
      adult patients, with previous repeated neurological and neuroradiological
      examinations, was studied by immunohistochemical and molecular biological
      methods. Samples from non-infected brains served as controls. METHODS:
      Immunohistochemistry with monoclonal antibodies (MAb) was combined with in situ
      RNA hybridization. Target cells were identified with MAb to glial fibrillary
      acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and Ricinus
      communis agglutinin (RCA-1; microglia, endothelial cells). For HIV, a panel of
      MAb against HIV Nef, Tat, Rev and Env proteins or probes specific for all classes
      of mRNA (nef), for singly or non-spliced mRNA (env) and for non-spliced mRNA
      (gag/pol) were used. RESULTS: Nef protein was detected in subcortical or subpial
      astrocytes in seven out of 14 samples, and in multinucleated giant cells in two
      cases. Gag/pol or env mRNA-expressing astrocytes were detected in four cases. In
      four out of five cases studied, HIV Rev, but not Tat, was also expressed in
      astrocytes. Six out of the seven patients with Nef-positive astrocytes had
      suffered from moderate to severe dementia. The patient with most rapidly
      progressing severe dementia showed extensive HIV mRNA expression together with
      Nef and Rev expression in astrocytes. CONCLUSION: In adult human brain,
      astrocytes are infected by HIV and preferentially express HIV Nef and Rev
      proteins but are also sometimes productively infected. Astrocyte infection is
      associated with moderate to severe dementia which agrees with recent knowledge on
      the housekeeping activities of astrocytes and their eventual role in learning and
      memory.

PMID- 8527072
TI  - Comparative assessment of small intestinal and colonic permeability in HIV
      infected homosexual men.
AB  - OBJECTIVES: To investigate both small and large intestinal permeability in HIV
      positive subjects, and correlate variation in intestinal mucosal abnormality with
      immunological and nutritional markers of HIV disease. METHODS: Small and large
      intestinal permeability studies were performed in 14 HIV-seropositive patients
      and eight healthy men. Eight out of the 14 patients had diarrhoea and all
      subjects were negative for enteropathogens. Small intestinal permeability was
      determined using the lactulose-mannitol test and large intestinal permeability
      using the colonic absorption of 51Cr-EDTA. In addition, CD4 cell count, beta 2
      microglobulin, C-reactive protein estimation and anthropometry were carried out
      in all subjects. RESULTS: HIV-seropositive subjects had higher lactulose-mannitol
      ratios (LMR; 0.084 +/- 0.007 versus 0.013 +/- 0.0008) and lower 51Cr activity
      (1.986 +/- 0.066 versus 3.115 +/- 0.560) than controls (P < 0.0004 and P < 0.05,
      respectively). Colonic uptake of 51Cr-EDTA was no different between subjects with
      and those without diarrhoea (2.04 +/- 0.124 versus 1.92 +/- 0.143, P > 0.05). A
      negative correlation was found between LMR and 51Cr-EDTA, but only for patients
      with diarrhoea (r = -0.81; P = 0.015). CONCLUSION: Regional variation affecting
      intestinal absorptive function occurs in patients with HIV-related diarrhoea and
      is characterized by increased LMR and reduced colonic uptake of 51Cr-EDTA. The
      pathogenesis and clinical significance of such changes are unknown.

PMID- 8527073
TI  - Generation of diversity in the hierarchy of T-cell epitope responses following
      different routes of immunization with simian immunodeficiency virus protein.
AB  - OBJECTIVES: To examine whether the route of immunization determines the hierarchy
      of T-cell epitope proliferative responses in macaques. DESIGN: Macaques were
      immunized with a recombinant simian immunodeficiency virus (SIV) p27 core protein
      by the intramuscular, male and female genital or rectal route, each of which was
      augmented by oral immunization, and by the novel targeted lymph-node immunization
      route. Overlapping peptides were used to identify the proliferative T-cell
      epitopes and to determine their hierarchy in the circulation, spleen and lymph
      nodes. METHODS: T-cell epitope mapping of the proliferative responses was studied
      in short-term cell lines. Dendritic cells and macrophages were enriched by
      metrizamide gradient and adherence to plastic, respectively. RESULTS:
      Intramuscular immunization elicited in the circulating T cells a hierarchy of T
      cell epitopes within four peptides in the following descending order of
      frequency: peptides 121-140 (57.9%), 41-60 (28.9%), 61-80 (18.9%) and 101-120
      (5.4%). The hierarchy of these four T-cell epitope responses differed
      significantly with each of the five routes of immunization, when circulating (P <
      0.001), splenic (P < 0.02-< 0.001) or iliac lymph-node cells (P < 0.001) were
      analysed. The effect of antigen-presenting cells was then investigated and
      enriched dendritic cells were more effective than macrophages in processing and
      presenting the p27 antigen and the immunodominant (121-140) and 61-80 T-cell
      epitopes. CONCLUSIONS: The route of immunization may determine the hierarchy of T
      cell epitopes in the lymph nodes draining the mucosa in the circulating and
      splenic lymphocytes. The diversity of T-cell epitopes may affect the control of
      HIV at different anatomical sites, the administration route of the vaccine, and
      selection of polypeptides or recombinant antigens for immunization.

PMID- 8527074
TI  - Zidovudine plus interferon-alpha versus zidovudine alone in HIV-infected
      symptomatic or asymptomatic persons with CD4+ cell counts > 150 x 10(6)/L:
      results of the Zidon trial. Zidon Study Group.
AB  - OBJECTIVE: To evaluate the efficacy and safety of zidovudine (ZDV) and
      lymphoblastoid interferon (IFN)-alpha combination therapy compared with ZDV
      monotherapy in HIV-infected subjects with CD4+ cell counts between 150 and 500 x
      10(6)/l. DESIGN: Open, randomized controlled trial with subjects stratified by
      the Centers for Disease Control and Prevention (CDC) 1986 classification of HIV
      disease (group II/III or IV). The study was amended to a sequential design in
      February 1992 to allow interim analyses to be conducted. SETTING: Outpatient
      clinics in 45 hospitals in Europe, Australia and Canada. PARTICIPANTS: A total of
      402 previously untreated subjects with symptomatic HIV infection (CDC group IV)
      and CD4+ count 150-500 x 10(6)/l or asymptomatic HIV infection (CDC group II/III)
      with CD4+ count 150-350 x 10(6)/l. INTERVENTIONS: ZDV 250 mg twice daily with or
      without 3 MU subcutaneous injections of lymphoblastoid IFN-alpha three times per
      week. MAIN OUTCOME MEASURES: Time to development of a study endpoint defined as:
      progression from CDC group II/III to group IV, group IV non-AIDS to AIDS, or
      group IV AIDS to a second AIDS-defining condition; also CD4+ count to < 50 x
      10(6)/l on two occasions at least 1 month apart or HIV-related death irrespective
      of CDC group on entry. RESULTS: There was no reduction in the rate of disease
      progression for patients receiving ZDV plus IFN-alpha compared with patients
      receiving ZDV alone. No major differences between the groups were seen for CD4+
      counts or percentages, or p24 antigenaemia. In a subset of 70 patients, a similar
      proportion from both dose groups showed evidence of ZDV resistance after 48 weeks
      of treatment. More adverse experiences were seen in the ZDV/IFN-alpha group.
      CONCLUSIONS: Combination therapy with low dose lymphoblastoid IFN-alpha and ZDV
      revealed no clinical benefit compared with ZDV monotherapy.

PMID- 8527075
TI  - Steroids do not enhance the risk of developing tuberculosis or other AIDS-related
      diseases in HIV-infected patients treated for Pneumocystis carinii pneumonia.
AB  - OBJECTIVE: To evaluate the risk of developing tuberculosis or other AIDS-related
      diseases (ARD) in HIV-infected patients treated with corticosteroids as
      adjunctive therapy for Pneumocystis carinii pneumonia (PCP). DESIGN:
      Retrospective study. SETTING: Infectious Disease Service of a 1000-bed university
      teaching hospital in Barcelona, Spain. PATIENTS: HIV-infected patients diagnosed
      with PCP from 1985 to 1992. Patients were classified into two groups: steroid
      (group A) and non-steroid (group B) adjunctive therapy. Baseline characteristics,
      antibiotherapy, dose and duration of steroidal treatment were analysed. Endpoints
      were either the development of tuberculosis or other ARD or death. RESULTS: From
      the 129 patients included in this study 72 were in group A and 57 in group B. No
      differences between groups were observed in baseline characteristics or mean
      follow-up period (15 versus 14 months, respectively). The mean total dose of
      steroids was 420 mg (range, 160-1260 mg) methylprednisolone or its equivalent in
      dexamethasone, with a mean treatment duration of 12 days (range, 4-33 days). No
      differences were found in the occurrence of tuberculosis or other endpoints in
      the first 6 months of follow-up. In addition, the cumulative rate of developing
      tuberculosis was 7% in group A and 12% in group B at 12 months of follow-up, and
      13 versus 12% at 24 months (P = 0.622, Mantel-Cox): 4 versus 4% at 12 months and
      27 versus 24% at 24 months (P = 0.873) for non-tuberculosis mycobacterial
      infection, and 40 versus 42% at 12 months, and 88 versus 66% at 24 months (P =
      0.330) for non-mycobacterial ARD. The cumulative survival rate was 79 versus 71%
      and 46 versus 34% at 12 and 24 months, respectively (P = 0.526). CONCLUSIONS: Our
      data suggest that the use of corticosteroids during PCP in HIV-infected patients
      at the doses and for the duration used in our patients did not enhance the risk
      of developing or relapsing tuberculosis or other ARD.

PMID- 8527076
TI  - Early central nervous system response to HIV infection: sleep distortion and
      cognitive-motor decrements.
AB  - OBJECTIVE: To repeat and extend findings suggesting that sleep disturbance,
      excessive daytime sleepiness, and degraded cognitive-motor abilities may be early
      markers of central nervous system (CNS) involvement in HIV infection. DESIGN: A
      controlled, cross-sectional, prospective analysis. SETTING: Clinical research
      center at a teaching hospital and a military health research center. SUBJECTS:
      Twenty-three HIV-positive (mean CD4+ count, 387 +/- 162 x 10(6)/l) and 13
      seronegative men who were Naval personnel or participants of the University of
      California, San Diego HIV Neurobehavioral Research Center. MAIN OUTCOME MEASURES:
      Nocturnal and daytime sleep electroencephalogram, electromyogram, and
      electrocardiogram. Simple and complex cognitive-motor performance assessed via
      computerized tasks. RESULTS: Comparison of sleep parameters based on HIV status,
      length of time infected, zidovudine use, and CD4+ count indicated that CD4+ T
      cells > 400 x 10(6)/l were associated with a distortion in nocturnal sleep
      characterized by increased stages 3 and 4 non-rapid eye movement (i.e., slow
      wave) sleep in the latter portion of the night and reduced nocturnal awakenings.
      HIV-positive patients were no sleepier in the daytime than controls. Cognitive
      motor performance revealed deficits in both accuracy and efficiency for HIV
      positive patients. CONCLUSION: Asymptomatic HIV-positive patients with CD4+
      counts > 400 x 10(6)/l demonstrate a statistically significant increase in slow
      wave sleep during the latter portion of the night and less arousability. CD4+
      lymphocyte count in the early phases of HIV infection appears to differentiate
      between various levels of HIV disease progression with respect to certain CNS
      measurements of nocturnal sleep and cognitive-motor performance. Sleep structure
      distortion remains one of the earliest and most consistently replicable
      physiological signs of HIV infection. This distortion may provide a link to
      immune function, disease progression, and cognitive-motor disability in HIV
      infection.

PMID- 8527077
TI  - Micronutrients and HIV-1 disease progression.
AB  - OBJECTIVE: To determine whether nutritional status affects immunological markers
      of HIV-1 disease progression. DESIGN: A longitudinal study, to evaluate the
      relationship between plasma levels of nutrients and CD4 cell counts, along and in
      combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month
      follow-up. METHODS: Biochemical measurements of nutritional status including
      plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and
      folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M]
      were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three
      6-month time periods. Changes in nutrient status (e.g., normal to deficient,
      deficient to normal), were compared with immunological parameters in the same
      time periods using an autoregressive model. RESULTS: Development of deficiency of
      vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P =
      0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12
      and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and
      0.0112, respectively). These findings were largely unaffected by zidovudine use.
      For vitamin B12, low baseline status significantly predicted accelerated HIV-1
      disease progression determined by CD4 cell count (P = 0.041) and the AIDS index
      (P = 0.005). CONCLUSIONS: These data suggest that micronutrient deficiencies are
      associated with HIV-1 disease progression and raise the possibility that
      normalization might increase symptom-free survival.

PMID- 8527078
TI  - HIV-1 and immunological changes during pregnancy: a comparison between HIV-1
      seropositive and HIV-1-seronegative women in Nairobi, Kenya.
AB  - OBJECTIVE: To assess changes in the proportion of CD4 and CD8 T-lymphocyte
      profiles during pregnancy, at delivery and postpartum, and to determine whether
      HIV-1 infection affects the normal profile. DESIGN AND METHODS: A total of 416
      pregnant HIV-1-infected women and an age and parity-matched HIV-seronegative
      group of 407 pregnant women were enrolled into a prospective study on the impact
      of HIV-1 infection on pregnancy. Maternal blood was obtained for lymphocyte
      subset determination at enrollment, delivery and 6 weeks postpartum. Whole blood
      sample drawn in EDTA-containing tubes were used to determine T-helper/inducer
      (CD4) and T-suppressor/cytotoxic (CD8) cells by direct immunofluorescence using
      monoclonal antibodies. RESULTS: No relationship was found between gestational age
      and any immunological variable. The CD4 percentage was lower postpartum than
      antenatally, in both HIV-1-seropositive and seronegative women, but this was not
      true for absolute CD4 counts. CD8 absolute counts and percentages were
      significantly higher postpartum than antenatally. The differences between HIV-1
      seropositive and seronegative women in changes over pregnancy in CD4 and CD8
      cells and their ratio, were not statistically significant. CONCLUSION: Our
      findings do not support a short-term synergistic effect of HIV-1 and pregnancy on
      the immune function as determined by T-lymphocyte subsets.

PMID- 8527079
TI  - Declining prevalence of HIV-1 infection in young Thai men.
AB  - OBJECTIVE: To evaluate trends in HIV-1 seroprevalence in Thailand. DESIGN: HIV-1
      serosurvey of successive cohorts of young Thai men entering service with the
      Royal Thai Army (RTA) between November 1989 and November 1994. METHODS: In
      November 1989, the RTA Medical Department began routine HIV-1-antibody screening
      of men who were selected by lottery for conscription. Between November 1989 and
      November 1994, 311,108 young men were screened at induction. Demographic data
      were collected between November 1991 and May 1993 and again in November 1994.
      RESULTS: The seroprevalence of HIV-1 among conscripts nationwide increased
      rapidly from 0.5% in 1989 to 3.5% in 1992 and reached 3.7% in 1993. In 1994, the
      overall prevalence decreased to 3.0%. The decrease was greatest in the upper
      North (from 12.4% in 1992 to 7.9% in 1994), where the prevalence has been the
      highest. However, decreases were observed in men from all regions of residence in
      the country, from both rural and urban areas, and at all educational levels.
      CONCLUSIONS: The decline in prevalence suggests declining incidence and that HIV
      control programs in Thailand are having an impact on the HIV epidemic.

PMID- 8527080
TI  - Declining risk for HIV among injecting drug users in Kathmandu, Nepal: the impact
      of a harm-reduction programme.
AB  - OBJECTIVE: To measure changes in self-reported risk behaviour for HIV infections
      and HIV seroprevalence among injecting drug user (IDU) clients of an outreach
      harm-reduction programme in Kathmandu, Nepal. METHODS: The Lifesaving and
      Lifegiving Society (LALS) of Kathmandu began providing sterile injecting
      equipment and education to Nepalese IDU in 1991. A sample of these IDU were
      interviewed and tested for HIV each year from 1991 through 1994. RESULTS:
      Indicators of unsafe injecting fell, as knowledge of HIV rose more in 1994 for
      those who had been in touch with LALS for longer. Indicators of unsafe sex did
      not change. HIV seroprevalence remained low, 1.6% in 1991 and 0% in 1994.
      CONCLUSION: We conclude that programmes for the prevention of HIV spread among
      IDU are possible and effective in Asia, and are urgently needed.

PMID- 8527081
TI  - HIV, sexually transmitted diseases and gynaecologic disorders in women: increased
      risk for genital herpes and warts among HIV-infected prostitutes in Amsterdam.
AB  - OBJECTIVES: To determine the incidence of sexually transmitted diseases (STD;
      gonorrhoea, early syphilis, Chlamydia trachomatis infection, trichomoniasis and
      primary genital herpes) and gynaecologic disorders (vaginal candidiasis,
      anaerobic vaginosis, genital ulcerations of unknown cause, pelvic inflammatory
      disease, recurrent genital herpes, recurrent genital warts) in a cohort of HIV
      infected and non-infected drug-using prostitutes in Amsterdam between 1986 and
      1992. DESIGN: A subgroup of 212 female drug users with a history of prostitution,
      who made at least one visit to a special STD clinic for drug-using prostitutes
      was selected from an ongoing cohort study of drug users in Amsterdam. METHODS:
      Using Poisson regression, the relative risk (RR) for each outcome was calculated
      for HIV-positive women compared with HIV-negative women. To determine potential
      causal relations with immune suppression, associations between disease incidence
      and immunologic markers (CD4 cell count and anti-CD3 response) were assessed in
      HIV-positive women. RESULTS: Adjusted for number of clients and frequency of
      condom use, HIV-positive women were at strong and significantly increased risk
      for primary genital herpes (RR, 7.64), recurrent herpes (RR, 8.33) and recurrent
      genital warts (RR, 15.93); moderately (significantly) increased risks were found
      for gonorrhoea (RR, 1.43), trichomoniasis (RR, 1.39), vaginal candidiasis (RR,
      2.11) and genital ulcers of unknown aetiology (RR, 2.60). Of these HIV-related
      outcomes, the risk for recurrent genital herpes and genital warts were strongly
      associated with decreased CD4 cell counts. CONCLUSIONS: HIV-infected women
      experience an excess morbidity of STD and gynaecologic disorders. The strongly
      increased risk for genital herpes and warts in HIV-seropositive women indicates a
      causal relation with HIV. This study emphasizes the need for accessible medical
      care for drug-using prostitutes.

PMID- 8527082
TI  - Willingness to participate in AIDS vaccine trials among high-risk populations in
      northern Thailand.
AB  - OBJECTIVES: To determine the anticipated participation in a prophylactic AIDS
      vaccine trial and to identify perceived benefits and barriers to enrollment of
      HIV-seronegative volunteers at risk of HIV infection in northern Thailand.
      DESIGN: A cross-sectional survey. METHODS: Subjects interviewed in a cross
      sectional survey included female commercial sex workers (n = 215), men attending
      sexually transmitted disease clinics (n = 219), conscripts in the Royal Thai Army
      (n = 1453), and men discharged from the army (n = 293) who had returned to
      civilian life. We determined AIDS vaccine knowledge and attitudes, perceived
      vulnerability to HIV infection, barriers and incentives to participate in a
      future vaccine trial and agreement to participate in a randomized trial. RESULTS:
      Awareness of vaccines (88-97%) and AIDS vaccine development efforts (62-77%) were
      common and viewed to be a complement to behavior change (74-94%). Approximately
      25% of subjects would definitely join a trial if asked, and an additional 38%
      would accept an AIDS vaccine if they were convinced it would be safe and
      effective. Important barriers to participation included concerns with
      discrimination (16-45%), short- (37-60%) and long-term (30-55%) vaccine side
      effects, fear of disability and death (36-58%), and beliefs that partners would
      refuse to have sex (24-49%) after immunization. The principal inducement to join
      a trial was health insurance (62%). CONCLUSION: Potential HIV vaccine trial
      participants have several fears of joining a vaccine study at this time.
      Information derived from Phase I/II trials is needed to address these concerns if
      enrollment in efficacy trials is to be successful in the near future.

PMID- 8527083
TI  - Lower prevalence and incidence of HIV-1 syncytium-inducing phenotype among
      injecting drug users compared with homosexual men.
AB  - OBJECTIVE: To study the prevalence, incidence and predictive value for
      progression to AIDS of the HIV-1 syncytium-inducing (SI) phenotype in HIV
      infected injecting drug users (IDU) compared with HIV-infected homosexual men.
      DESIGN: Two prospective cohort studies on HIV-1 infection among IDU and
      homosexual men. METHODS: HIV-infected IDU (n = 225) and homosexual men (n = 366)
      without AIDS were studied from March 1989 through December 1993. Data on
      laboratory markers, including the presence of SI variants, demographics,
      behavioural characteristics and clinical events were collected at every visit.
      RESULTS: At baseline, SI variants were detected in 4% of IDU and 17% of
      homosexual men. During the study period 18 IDU and 68 homosexual men switched
      from non-SI to SI phenotype (4-year cumulative incidence, 14.6 and 28.4%,
      respectively) before AIDS diagnosis. Among participants with a documented date of
      HIV infection the cumulative incidence of SI was lower among IDU than homosexual
      men (4-year cumulative incidence, 6.2 and 20.7%, respectively). At AIDS
      diagnosis, 21% of all AIDS cases among IDU had the SI phenotype compared with 54%
      among homosexual men. In both risk groups an accelerated CD4 decline was found
      after the non-SI-to-SI switch. The SI phenotype appeared to be a predictor of
      AIDS (multivariate relative hazard, 5.33), independent of CD4 cell count and p24
      antigen at baseline. In the multivariate time-dependent analysis, the relative
      hazard of SI phenotype decreased considerably, which is consistent with the
      hypothesis that the effect of SI phenotype on progression to AIDS is mediated by
      CD4 cell count. CONCLUSION: The SI phenotype is associated with accelerated CD4
      decline and progression to AIDS in both risk groups. The remarkable lower
      prevalence and incidence of the SI phenotype among IDU may implicate a difference
      in pathogenesis and natural history of HIV infection linked to transmission
      group.

PMID- 8527084
TI  - Bacterial vaginosis and HIV seroprevalence among female commercial sex workers in
      Chiang Mai, Thailand.
AB  - OBJECTIVE: To investigate the relationship between HIV seropositivity and
      bacterial vaginosis (BV) in a population at high risk for sexual acquisition of
      HIV. DESIGN: A cross-sectional study was conducted among 144 female commercial
      sex workers in Chiang Mai, Thailand. METHODS: The participants were tested for
      cervical gonorrhea and Chlamydia infection, syphilis, Trichomonas vaginitis,
      Candida vaginitis, BV, and HIV infection. BV was diagnosed by clinical criteria
      (pH > 4.5, positive amine test, and presence of clue cells) and using Gram
      stains. RESULTS: Thirty-three per cent of participants had BV, and 43% were HIV
      positive. Using clinical criteria, the association of BV and HIV seropositivity
      was significant [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.3-5.0].
      Although the association between BV and HIV prevalence was not significant using
      Gram stains alone for diagnosis of BV, an association was found between abnormal
      vaginal flora and HIV (OR, 2.1; 95% CI, 1.0-4.8). In multiple logistic regression
      analysis, adjusting for age, number of sexual encounters per week, current condom
      use, and currently having a sexually transmitted disease (STD), both BV and a
      history of an STD were independently associated with HIV seropositivity (adjusted
      OR for BV, 4.0 and 95% CI, 1.7-9.4; adjusted OR for history of an STD, 6.9 and
      95% CI, 2.1-22.9). CONCLUSIONS: When diagnosed clinically, BV is independently
      associated with HIV seroprevalence. HIV infection may promote abnormal vaginal
      flora, or BV may increase susceptibility to sexual transmission of HIV.
      Alternatively, the association seen here may result from intervening variables;
      in this case BV may be a marker or a cofactor of HIV transmission.

PMID- 8527085
TI  - Increased cerebrospinal fluid levels of soluble receptors for tumour necrosis
      factor in HIV-infected patients with neurological diseases.

PMID- 8527086
TI  - Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in AIDS
      dementia complex.

PMID- 8527087
TI  - Diffuse infiltrative CD8 lymphocytosis syndrome with predominant neurologic
      manifestations in two HIV-infected patients responding to zidovudine.

PMID- 8527088
TI  - Detection of HIV-1 in surgical specimens from vitreous of AIDS patients.

PMID- 8527089
TI  - HIV saliva test for surveillance and surveys.

PMID- 8527090
TI  - Syringe cleaning techniques and transmission of HIV.

PMID- 8527091
TI  - Effects of megestrol acetate therapy on body composition and circulating
      testosterone concentrations in patients with AIDS.

PMID- 8527092
TI  - The importance of patients' own view about their quality of life.

PMID- 8527093
TI  - Changing prevalence of hepatitis B virus and hepatitis D virus infection among
      injecting drug users in Hong Kong indicating a change in high-risk behaviour.

PMID- 8527094
TI  - Genetic therapies for HIV infections: promise for the future.

PMID- 8527095
TI  - Nuclear translocation of an exogenous fusion protein containing HIV Tat requires
      unfolding.
AB  - OBJECTIVE: To characterize the transcellular transport of HIV-1 Tat. HIV-1 Tat
      contains a putative localization signal and no leader peptide; however, it can be
      released from virus-infected cells and taken up by uninfected cells. DESIGN AND
      METHODS: We constructed a chimeric protein between Tat and dihydrofolate
      reductase (DHFR), a cytosolic enzyme that binds tightly to the folate analogue
      methotrexate (MTX). As confirmed by protease sensitivity assays, binding to MTX
      results in stabilization of the three-dimensional structure of the DHFR domain.
      The nuclear translocation of recombinant proteins was monitored by both
      functional [transcellular transactivation of a long terminal repeat
      chloramphenicol acetyl transferase (LTR-CAT) reporter gene] and biochemical
      (subcellular localization in HeLa cells of exogenous radiolabelled proteins)
      assays and the effects of MTX-induced stabilization were evaluated. RESULTS: When
      in vitro translated proteins are added to HeLa cells in culture, both wild-type
      Tat and the chimeric protein Tat-DHFR are taken up by target cells and accumulate
      in the nucleus, unlike wild-type DHFR. Cells transfected with Tat-DHFR, when co
      cultured with cells harbouring a LTR-CAT gene, induce transactivation of the
      reporter gene to the same extent as cells expressing wild-type Tat. These
      findings indicate that Tat can mediate the internalization of unrelated
      polypeptides. Pre-treatment of Tat-DHFR with MTX blocks the nuclear translocation
      of the chimeric protein. MTX has no effect on wild-type Tat. CONCLUSION: HIV-1
      Tat can act as a vector to drive polypeptides into the nucleoplasm of living
      cells. The inhibitor effects of MTX on the nuclear localization of Tat-DHFR
      suggest that an unfolding step is required for the internalization of exogenous
      Tat.

PMID- 8527096
TI  - Redetermination of sodium cerium(III) sulfate monohydrate, NaCe(SO4)2.H2O.
AB  - The structure of sodium cerium sulfate monohydrate, NaCeIII(SO4)2.H2O, comprises
      distorted NaO6 octahedra, CeO9 polyhedra in the form of distorted tricapped
      trigonal prisms, and slightly irregular tetrahedral sulfate ions. This structure
      is isomorphic with that of NaLaIII(SO4)2.H2O. All bonds fall within normal
      limits. The sulfate ion manifested rigid-body behavior but neither of the cation
      complexes did. As in the previous structural analysis of the La analog [Blackburn
      & Gerkin (1994). Acta Cryst. C50, 835-838], the water molecule is modelled as
      having O-atom disorder but with an ordered H atom. Hydrogen bonds involve only
      sulfate O atoms as acceptors. The anisotropic atomic displacement parameters are
      found to be in good agreement with the corresponding parameters determined for
      the La analog, but in poor agreement with those previously reported for the title
      salt by Lindgren [Acta Chem. Scand. Ser. A, (1977), 31, 591-594]. Taken together,
      the data establish that the lack of correction for absorption in the previous
      study of the Ce salt, rather than some intrinsic property of the Ce salt, is
      responsible for the displacement parameter discrepancies. The absolute structure
      has been determined.

PMID- 8527097
TI  - Molecular stereochemistry of [FeIII(TPP)(OCOCF3)].
AB  - (meso-Tetraphenylporphinato)(trifluoroacetato)iron(III), [Fe(C2F3O2)(C44H28N4)],
      consists of a central Fe atom equatorially coordinated to four pyrrole N atoms
      and axially coordinated th an O atom of the trifluoroacetate group. The average
      Fe--N bond distance is 2.054(5)A and the Fe atom is displaced 0.483 (1) A from
      the porphinato plane. The Fe--O distance is 1.921 (4) A. The out-of-plane
      displacement and the Fe--N bond lengths indicate that the Fe atom is in a high
      spin state.

PMID- 8527098
TI  - The cyclic depsipeptide backbone of the didemnins.
AB  - An X-ray crystal analysis of phi-lactone N-?1-?N-?4-?[3- hydroxy-5-methyl-1-oxo-4
      (N-L-threonylamino)heptyl]- oxy?-2,5-dimethyl-1,3-dioxohexyl?-L-leucyl?-L-prolyl?
      N,O-dimethyl-L-tyrosine hydrobromide hydrate (1a), C42H66N5O11+.Br-.H2O, was
      obtained in order to determine the backbone folding of the macrocycle and to
      compare the results obtained with those reported previously for the natural
      product didemnin B (1b). Some differences were noted in the torsion angles of the
      two conformers of the hydrobromide salt, denoted (1a) and (1a'). The conformation
      of (1a') resembled the conformation of (1b) more closely than did that of (1a).
      Certain regions of both crystal backbones were more flexible than those in
      didemnin B; however, the transannular hydrogen bonds in both (1a) and (1a') were
      somewhat stronger than in (1b).

PMID- 8527099
TI  - Thiodicarb.
AB  - Dimethyl N,N'-[thiobis(methyliminocarbonyloxy)] bis-(ethanimidothiolate),
      C10H18N4O4S3, is an example of a sulfenylated biscarbamate insecticide. The
      molecule has an approximate twofold axis through the central S atom which joins
      the two methyliminocarbonyloxyethanimidothiolate units. One of the two arms is
      planar in the crystal. Semi-empirical geometry optimization for an isolated
      molecule favors a model with both arms planar and, thus, crystal packing may be
      responsible for the observed non-planarity in one arm. Bond lengths and angles
      have similar values to those of the 'monomeric' carbamate insecticide methomyl.

PMID- 8527100
TI  - [Propolis: its use in technology and research].
AB  - Analytical procedure more advanced allowed to identify, to isolate, and assay the
      compounds present in propoli which is is developed to be a valuable biological
      product as food resource as medical resource. Analytical procedure more and more
      sophisticated allowed (us) to assay the propoli composition without operate the
      derivatization of phenolic constituents making use the capacity of different
      detector used. These phenolic contents were analysed by capillary gas
      chromatography using an electron-capture detector. This detector shown a good
      electron capture response of these compounds, which belong to the so-called
      "conjugated electrophores".

PMID- 8527101
TI  - Novel pyrimidinediones and thiazolidinones as anti depressants.
AB  - 2-Mercapto-5-[4'-methoxy phenyl thiourea]-1,3,4-thiadiazole (2a-c) prepared by
      the condensation of 2-amino-5-mercapto-1,3,4-thiadiazole (1) with substituted
      phenyl isothiocyanates. Further on cyclisation with malonic acid in the presence
      of acetyl chloride gave the corresponding 2-mercapto-5-[3-(4-methoxy phenyl)-2
      thioxo-2-5-dihydro-4, 6-pyrimidionoyl]-1,3,4-thiadiazole (3a-c) [sequence: see
      text]. This on further reaction with substituted aryl aldehydes in presence of
      zinc chloride gave 2-mercapto-5-[3-(4'-methoxy phenyl)-2'-thioxo-2',5'-dihydro
      4',6' -pyrimidionoyl 5'-phenyl carboxaldehyde]-1,3,4- thiadiazole (4a-g)
      [sequence: see text]. The compounds were screened for antidepressant activity and
      compared with antidepressant (imipramine).

PMID- 8527102
TI  - Stability-indicating high performance liquid chromatographic method for
      determination of norfloxacin in bulk form and tablets.
AB  - High performance liquid chromatographic (HPLC) separation has been investigated
      for the determination of intact norfloxacin in the presence of its
      photodegradation products. The HPLC-separation could be achieved isocratically
      and by gradient elution on a Micropak -NH2 column (10 microns, 30 cm x 4 mm O)
      using a mobile phase containing acetonitrile, tetrabutylammonium hydroxide, o
      phosphoric acid and water at a rate of 2 ml.min-1 with UV-detection (278 nm) at
      ambient temperature. The method was applied for the drug analysis in fresh and
      photodegraded norfoxacin samples, as well as for assessment of the content
      uniformity of tablets containing the drug. The results of the proposed liquid
      chromatographic method were statistically matched with those obtained by adopting
      an official HPLC-method (USP XXII-procedure).

PMID- 8527103
TI  - Potentially active antimicrobial agents from 2-benzenesulfonyloxyphenyl-3,1
      benzoxazine-4-one derivative.
AB  - Fourteen of nitrogeneous heterocyclic compounds that accommodate the sulfonate
      ester moiety were synthesized through interaction of 2-benzenesulfonylo xyphenyl
      3,1-benzoxazine-4-one with some nucleophilic reagents. The assigned structures
      for the prepared new compounds were confirmed on the basis of elemental and
      spectral data. Evaluation of the antimicrobial activity of these products,
      relative to standard antibiotics was tested and discussed.

PMID- 8527104
TI  - In vitro efficacy evaluation of cosmetic products: a pool of tests on cultured
      cells.
AB  - The efficacy of cosmetic products and active substances have been investigated on
      human keratinocytes cell line on a pool of tests. The work aimed to study the
      possible modifications of the biological parameters tested (cytotoxicity and
      cytoskeleton morphology) related to the cellular adhesion function. The results
      have permitted to define different activities, for the different products,
      compared to the untreated culture and to their placebo.

PMID- 8527105
TI  - Antimalarial activity of oxidized starch and cellulose imine derivatives.
AB  - With the purpose of screening potential antimalarial agents, oxidized starch
      imine derivatives of sulfonamides or pyrimidine - derivatives of sulfisoxazole
      (ML8), sulfameter (ML11) and trimethoprim (ML13) - and oxidized cellulose imine
      derivatives of dapsone (ML14), sulfadiazine (ML17), sulfamethoxazole (ML18),
      sulfisoxazole (ML19), sulfamethoxypyridazine (ML20) and sulfameter (ML22) were
      submitted to in vivo biological assays with mice infected with Plasmodium
      berghei. Only ML11 was 100% curative in test conditions; ML 17 showed the same
      effect as its prototype. The drug content in both prodrugs is lower in the
      applied dose than that used in the original drugs. It can be suggested that the
      latentiation enhanced the effectiveness of the prototypes.

PMID- 8527106
TI  - [Controversial developments in AIDS].

PMID- 8527107
TI  - Low spinal and pelvic bone mineral density among individuals with Down syndrome.
AB  - The bone mineral density of 15 adults with Down syndrome was compared to 25
      control subjects without Down syndrome. Bone mineral density was measured by dual
      x-ray absorptiometry with a Lunar DPX scanner. Arm, leg, pelvic, and spine bone
      mineral density was tested. Analysis of covariance was conducted for each
      variable; Down syndrome was the independent variable, and the covariates were
      height, lean body mass, fat mass, age, and gender. No significant group
      differences were found for arm or leg bone mineral density. Individuals with Down
      syndrome had significantly lower pelvic and spinal bone mineral density. Before
      adjustment for covariates, percentage difference between group means for spine
      was 14.5% and for pelvis, 11.6%. Adjusted percentage was 11.1% and 13.9%,
      respectively. Suggestions for further research were made.

PMID- 8527108
TI  - Effects of children with Down syndrome on parents' activities.
AB  - Effects of children with Down syndrome on parents' daily activities were
      investigated. Data on the allocation of time to daily activities were obtained
      from time diaries provided by two samples of parents with at least one child
      under age 17. Parents in one sample had a child with Down syndrome and parents in
      the other sample did not. Comparison of time allocations by sample indicated that
      parents of children with Down syndrome differed substantially from other parents
      in their patterns of time use. Both parents of a child with Down syndrome devoted
      more time to child care and spent less time in social activities. Mothers of
      children with Down syndrome allocated less time to paid employment.

PMID- 8527109
TI  - Attention regulation by children with Down syndrome: coordinated joint attention
      and social referencing looks.
AB  - We examined attention regulation of children in two different situations designed
      to elicit triadic interactions (i.e., between self, other, and object). Thirty
      five children with Down syndrome and 23 children with typical development were
      observed in a semi-structured adult-child interaction designed to elicit
      coordinated joint attention and an ambiguous situation in which a moving robot
      prompted an emotional response from the adults in order to elicit social
      referencing looks from the child. Children with Down syndrome engaged in
      significantly fewer social referencing looks. Group differences were not found
      for coordinated joint attention looks, suggesting that the difficulty for
      children with Down syndrome is in cognitive appraisal abilities.

PMID- 8527110
TI  - Relative prevalence and relations among stereotyped and similar behaviors.
AB  - Relative prevalence and relations among stereotyped and similar behaviors were
      studied in 246 children and adults with developmental disabilities. For each
      subject, two staff members who knew the participant at least moderately well
      filled out a checklist of 54 items that sampled various forms of stereotyped
      behaviors, abnormal focused affections, compulsions, rigidity, savant skills, and
      defensiveness. Agreements between raters for individual participants were low to
      moderate. However, the item prevalence scores for the two groups of observers
      were stable. Correlations between several items were significant. Factor analyses
      produced weak evidence for a general Stereotypy factor and further evidence for 6
      to 8 subfactors, some of which are generally consistent with accepted
      classification of the types of behaviors studied here.

PMID- 8527111
TI  - Event-related potentials and information processing in infants with and without
      Down syndrome.
AB  - Event-related brain potentials (ERPs) were recorded from 6-month-old infants with
      and without Down syndrome presented with a visual recognition memory task. The
      ERP morphology was the same for both groups. The chronometry of information
      processing by infants with Down syndrome was similar to or faster than that of
      the infants without Down syndrome, depending on ERP component. The amplitude
      differences between groups may implicate frontal attentional processes in Down
      syndrome as opposed to more posterior processes. Infants with Down syndrome had
      an amplitude decrement in Nc over the central but not frontal cortex. The infants
      with Down syndrome also had similar visual fixation. Infants may have more subtle
      differences than those found in older individuals with Down syndrome.

PMID- 8527112
TI  - Use of pointing and other gestures by young children with Down syndrome.
AB  - Pointing, reaching, and other communicative gestures were elicited from 22
      children with Down syndrome ages 21 to 47 months in two communicative contexts
      (referential/declarative vs. instrumental/imperative) and with two partners
      (mother vs. agemate with Down syndrome). Linguistic competence was assessed using
      the Vineland and Reynell Scales. High levels of pointing were produced in both
      communicative contexts and with each partner. Advance visual checking of the
      partner appeared to indicate awareness of the necessary conditions for successful
      declarative pointing. Comparisons with matched data from typically developing
      infants revealed both similarities and differences in gesture use. Findings were
      discussed in relation to delayed language development in children with Down
      syndrome.

PMID- 8527113
TI  - Compulsions in adults with mental retardation: prevalence, phenomenology, and
      comorbidity with stereotypy and self-injury.
AB  - A variety of conceptual similarities between compulsions seen in individuals with
      obsessive compulsive disorder and stereotypy and self-injury seen in individuals
      with mental retardation led us to investigate the prevalence, phenomenology, and
      comorbidity of compulsions in adults with severe or profound mental retardation.
      We developed simple assessment screening instruments for stereotypy and self
      injury and used Gedye's Compulsive Behavior Checklist and found acceptable levels
      of reliability, stability, and validity for each instrument. Prevalences were as
      follows: stereotypy: 60.9%; self-injury: 46.6%; and compulsion: 40%. The
      occurrence of compulsions was significantly positively associated with the
      occurrence of stereotypy, self-injury, and stereotypy plus self-injury.

PMID- 8527114
TI  - Evaluating psychotropic drugs in people with mental retardation: where are the
      social validity data?
AB  - In general, social validity data reflect the social significance of target
      behaviors, the appropriateness of procedures, and the perceived importance of
      results. These data are important insofar as they predict whether a given
      intervention will be used and, if used, whether consumers are likely to be
      satisfied with it. Despite the importance of social validity data, a survey of
      articles published from 1987 through 1993 in five major journals revealed that
      none of the 68 articles concerned with the psychopharmacology of mental
      retardation reported social validity data.

PMID- 8527115
TI  - Preventing restrictive placements through community support services.
AB  - A policy evaluation of Community Support Services, an assistance group created by
      the Minnesota Department of Human Services to prevent admission of individuals
      with developmental disabilities to large state facilities, was presented. The
      model of these out-reach services was described. Program evaluation data were
      presented. The possible effect of Community Support Services on admissions to
      large state facilities, characteristics of individuals served compared to those
      waiting for these services, cost-benefit issues of operating Community Support
      Services, and community service providers' satisfaction with these services were
      discussed. Issues related to the establishment and operation of Community Support
      Services were also presented.

PMID- 8527116
TI  - Discontinuation of neuroleptics in community-dwelling individuals with mental
      retardation and mental illness.
AB  - Many individuals with mental retardation and mental illness who are on
      neuroleptics can have the dose reduced or discontinued. A recent study, however,
      suggests that individuals with psychosis not only may be difficult to discontinue
      from neuroleptics but also may require an increased neuroleptic dose. The current
      study is a retrospective chart review. Individuals were followed for 12 months
      postneuroleptic discontinuation. Individuals with a "psychotic" disorder were
      significantly more likely to be restarted on neuroleptics at 3 months and 12
      months. A logistic regression failed to reveal any psychotic symptoms that
      predicted resumption on neuroleptics. An absent history of delusions, however,
      was significantly associated with remaining neuroleptic-free at 3 months.

PMID- 8527117
TI  - Not all institutional dental care has remained static.

PMID- 8527118
TI  - A collaborative study on DNA quantitation in biological products.
AB  - In 1988, a collaborative study was set up to examine the sensitivity and
      reproducibility of assays for the detection of DNA in biologicals derived from
      continuous cell lines. Fifteen laboratories analyzed 12 samples containing
      different amounts of DNA and protein. When no or very little DNA was present in
      the test samples, false positives or overestimation was common. In contrast, when
      higher levels of DNA were present underestimation was the norm. The study also
      revealed a high degree of variability between laboratories.

PMID- 8527119
TI  - Inactivation of DNA by beta-propiolactone.
AB  - beta-propiolactone (BPL) is an alkylating agent which reacts with many
      nucleophilic reagents including nucleic acids and proteins. BPL modifies the
      structure of nucleic acids after reaction mainly with purine residues (notably
      guanine). It induces nicks in DNA, cross-linking between DNA and proteins as well
      as between the DNA strands in the double helix. Consequently, BPL is widely used
      for the inactivation of viruses (DNA and RNA viruses). Moreover, it alters the
      capability of residual/contaminating cell DNA to be used as template by various
      polymerases. Thus, BPL reduces the risks associated with residual/contaminating
      cell DNA in biologicals.

PMID- 8527120
TI  - Evaluation by polymerase chain reaction on the effect of beta-propiolactone and
      binary ethyleneimine on DNA.
AB  - Inactivating treatments for viruses such as pasteurization or alkylation by beta
      propiolactone or binary ethyleneimine were tested for their capacity to modify
      nucleic acids. The modification of a nucleic acid was measured as the decrease in
      spot intensity in Southern blots after polymerase chain reaction (PCR)
      amplification. The inactivating treatments were applied to cellular and viral
      genomic material from a human lymphoblastoid cell line immortalized by Epstein
      Barr Virus (EBV), which produced a monoclonal antibody. Pasteurization did not
      modify the ability to amplify and detect cellular or viral DNA. Binary
      ethyleneimine strongly reduced the amount of detectable DNA and beta
      propiolactone under particular conditions of incubation abolished all trace of
      DNA.

PMID- 8527121
TI  - Administration of tumor cell chromatin to immunosuppressed and non
      immunosuppressed non-human primates.
AB  - For decades, developers and regulators of vaccines and other biological products
      have been concerned about the theoretical risk to patients posed by contaminants
      derived from the cell substrates used to produce those products. The present
      study addresses the issue of how risky DNA may be as a residual impurity by
      injecting both normal and immunosuppressed monkeys with 10(8) genome equivalents
      of DNA from a human tumor cell line. After more than eight years of observation,
      none of the animals shows evidence of neoplastic disease. The results of this
      study along with clinical experiences with already approved products derived from
      continuous cell lines suggest that he benefits of using such cells for the
      production of biologicals far outweigh any theoretical risks associated with DNA.

PMID- 8527122
TI  - Viral vaccines and residual cellular DNA.
AB  - The acceptability of viral vaccines manufactured in culture of continuous cell
      lines opened the way to a new technology of vaccine preparation. The large scale
      cultivation of continuous cell lines contributed greatly to the improvement of
      the safety and the consistency of viral vaccines. Experimental studies concerning
      residual cellular DNA and its oncogenic potential showed clearly that this
      material is not able to induce tumours. The small amounts of cellular DNA present
      in the final product, and the deleterious effect of the vaccine manufacturing
      process on the integrity and biological activity of DNA, both contribute to
      regarding residual cellular DNA as an issue of no practical importance. There is
      no evidence that limits on the concentration of residual cellular DNA in the
      final product is scientifically justified.

PMID- 8527123
TI  - DNA in plasma of human blood for transfusion.

PMID- 8527124
TI  - DNA, dragons and sanity.

PMID- 8527125
TI  - Use of monoclonal antibodies in the standardization of Parietaria judaica
      allergenic extracts.
AB  - Two monoclonal antibodies (MoAb) specific for Parietaria judaica allergenic
      components were selected on the basis of their capability to recognize either the
      Parietaria judaica major allergen (MoAb 1A6/1D1) or several other allergenic
      components (MoAb 1A4/2F8) except the major allergen. These two antibodies, either
      individually or combined, were used to develop an ELISA-inhibition system using a
      reference Parietaria judaica extract (in-house Reference preparation, IHR). The
      assays performed with these reagents were firstly standardized by testing the IHR
      several times. A good reproducibility, evaluated both at the level of 50%
      inhibition values, and in terms of analysis of the variance of the slopes of the
      regression curves, was obtained. Subsequently, the potency of several Parietaria
      judaica extracts, either obtained by manufacturing companies or produced in other
      laboratories, was evaluated by these tests. Data obtained by interpolation with
      the IHR values and expressed in terms of arbitrary units (AU) were compared with
      those obtained by classical human IgE inhibition, performed with sera from
      allergic patients. Results indicate that the monoclonal antibodies produced in
      our laboratory can be successfully employed, either individually or combined, in
      the standardization of allergenic preparations in addition to, and possibly
      replacing, the classical IgE-based standardization procedures which require human
      specimens often available in limited amounts only.

PMID- 8527126
TI  - Observations on the effect of the diluent used for diluting challenge toxin in
      the Clostridium botulinum potency test.
AB  - Clostridium botulinum vaccines were assayed for potency according to the method
      described in the European Pharmacopoeia. This method uses 20 white mice which are
      vaccinated with a dilution of vaccine in 0.9% saline. Twenty-one days later the
      vaccinated mice and ten unvaccinated control mice are challenged with C.
      botulinum toxin and observed for 7 days. In this study the challenge toxin was
      diluted in two separate diluents, 0.9% saline and peptone broth. More
      reproducible results were achieved with peptone broth as the diluent.

PMID- 8527127
TI  - Criteria for investigation of the product equivalence of monoclonal antibodies
      for therapeutic and in vivo-diagnostic use in case of introduction of changes in
      the manufacturing process.
AB  - The development of a monoclonal antibody for therapeutic or in vivo-diagnostic
      use from the first description to clinical trials and compilation of the dossier
      for granting the license requires a time consuming and expensive program. Due to
      its long development time, a particular monoclonal antibody can be subjected to a
      series of changes and improvements in manufacturing technology before licensure.
      In addition, the application for marketing authorization of biotechnology-derived
      medicinal products is not to be considered as an endpoint of a drawn-out
      development process which ends with license, because changes, amendments or
      improvements of the manufacturing process occur after a marketing authorization
      for a monoclonal antibody has been granted. Most of these changes, even minor
      qualitative and quantitative changes in the active substance itself, would
      require a new application according to the legal regulations of the European
      Union and of the national drug laws of the Member States. The paper proposes a
      procedure to take previously evaluated development-related data into account by
      evaluation of the product equivalence of both antibody forms ascertained before
      and after introduction of changes in the manufacturing process. The thorough in
      vitro analysis of parameters such as isotype, subclass, affinity,
      microheterogeneity, molecular weight, primary and secondary structure, structural
      integrity of the antibody molecule, glycosylation pattern, specificity, cross
      reactivity and biological potency with subsequently performed
      pharmacological/toxicological evaluation of biodistribution, half life and safety
      provide sufficient data for decision on the need for further clinical trials.

PMID- 8527128
TI  - Some thoughts on the children's vaccine initiative.

PMID- 8527129
TI  - Method for sequencing foreign genes expressed from the polyhedrin promoter of
      recombinant baculoviruses.

PMID- 8527130
TI  - Sensitive procedure for the amplification of HIV-1 RNA using a combined reverse
      transcription and amplification reaction.

PMID- 8527131
TI  - Enzymatically produced composite primers: an application of T4 RNA ligase-coupled
      primers to PCR.

PMID- 8527132
TI  - Improvement of the gene splicing overlap (SOE) method.

PMID- 8527133
TI  - Direct molecular analysis of archival tumor tissue for loss of heterozygosity.

PMID- 8527134
TI  - Isolation of intact nuclei for nuclear extract preparation from a fragile B
      lymphocyte cell line.

PMID- 8527135
TI  - Improved high-level expression system for eukaryotic genes in Escherichia coli
      using T7 RNA polymerase and rare ArgtRNAs.

PMID- 8527136
TI  - Improved expression of toxic proteins in E. coli.

PMID- 8527137
TI  - "Waterbug" dialysis.

PMID- 8527138
TI  - Using Lego bricks to cast horizontal electrophoresis gels.

PMID- 8527139
TI  - Value of A260/A280 ratios for measurement of purity of nucleic acids.

PMID- 8527140
TI  - Stripping of digoxigenin-labeled probes from nylon membranes.

PMID- 8527141
TI  - Efficacy of tetracycline-controlled gene expression is influenced by cell type:
      commentary.

PMID- 8527142
TI  - Isolation of viroid-RNA-binding proteins from an expression library with
      nonradioactive-labeled RNA probes.
AB  - The detection and isolation of cDNAs of tomato proteins that are able to bind to
      viroid RNA molecules are described. They were found by screening of a lambda gt11
      cDNA expression library using a modification of the previously established ligand
      blotting procedure to detect DNA- and RNA-binding proteins. The essentials of our
      modifications are the use of (i) digoxigenin-labeled viroid RNA, (ii) low
      concentration of the labeled probes and (iii) an expression library that allows
      the direct isolation of cDNA clones. The analysis of various isolated clones
      showed that this method is reliable for RNA-ligand screening and North-Western
      blotting. Applied to viroid RNA, these experimental tools provide the
      precondition for further studies on the specificity of the isolated proteins.

PMID- 8527143
TI  - Nonradioactive detection of hypervariable simple sequence repeats in short
      polyacrylamide gels.
AB  - A method for resolving and visualizing genotypes for simple sequence repeat loci
      on short (20 cm) polyacrylamide gels is described. This method makes use of a
      modified vertical electrophoresis cell to allow rapid electrophoresis without
      variation in migration rates due to uneven gel heating. Gels are stained with
      SYBR Green to visualize and photograph bands on an ultraviolet transilluminator,
      thereby eliminating the need for traditional radioisotope labeling of PCR
      products for autoradiography.

PMID- 8527144
TI  - Anion-exchange HPLC analysis of biotinylated oligonucleotides.
AB  - Biotinylated oligonucleotides combined with streptavidin-coated magnetic beads
      are commonly used in current molecular biology. Their quality and the level of
      incorporated biotin are essential for yielding good results in either solid-phase
      DNA sequencing or solid-phase purification procedures. This paper presents a very
      simple analytical test using anion-exchange HPLC and avidin to ascertain the
      quality of biotinylated oligonucleotides and to predetermine their ability to
      bind to avidin, which is a prerequisite for functionality in some solid-phase
      methods.

PMID- 8527145
TI  - Rapid microplate mitogenic assay using a meltable scintillation wax.
AB  - To combine the advantages of solid scintillation and the use of 96-well plates,
      an in-plate cell proliferation assay was designed using scintillation wax. Messy,
      conventional liquid wastes are not produced, thereby making solid scintillation
      safer and more convenient. Additionally, the use of optimized, 96-well ViewPlates
      for inplate counting procedures allows the monitoring of cell morphology during
      the course of the stimulation experiment. The scintillation wax, FlexiScint, was
      used for counting [3H]thymidine incorporation in an adherent cell line and
      compared to liquid scintillation counting. The data presented here demonstrate
      that this new assay produces results comparable to those obtained by conventional
      methods.

PMID- 8527146
TI  - Combining optical and atomic force microscopy for life sciences research.
AB  - The atomic force microscope (AFM), a three-dimensional imaging tool that can
      measure structures from the atomic level to micron scale, has been combined with
      an inverted optical microscope capable of confocal imaging. The robust design of
      this microscope, termed the BioScope, enables the operator to use fluorescent
      markers on a wide variety of biological specimens to determine internal structure
      to 200 nm resolution and determine surface morphology of the same sample to 20 nm
      resolution while imaging under physiological conditions. In this report we
      demonstrate the capabilities of the BioScope by examining living Xenopus retinal
      glial (XR1) cells, Drosophila polytene chromosomes and colloidal gold-labeled
      plasmid DNA.

PMID- 8527147
TI  - Amplification of 18 dystrophin gene exons in DMD/BMD patients: simultaneous
      resolution by capillary electrophoresis in sieving liquid polymers.
AB  - Duchenne (DMD) and Becker (BMD) muscular dystrophies are the two most common
      myopathies described so far. In the late 80s, Chamberlain et al. and Beggs et al.
      proposed two PCR assays allowing detection of over 98% DMD/BMD deletions. Since
      each of them is based on specific co-amplification of 9 dystrophin gene exons, a
      method attempting simultaneous analysis of DMD/BMD should offer unambiguous
      resolution and identification of 18 DNA fragments ranging in size from
      approximately 100 to 500 bp. We have developed a novel capillary electrophoresis
      method that allows simultaneous analysis of the two PCR sets with full diagnostic
      value. It consists of (a) an ultrastable inner capillary coating based on a novel
      acrylamide monomer (N-acryloyl amino ethoxy ethanol); (b) a very low viscosity
      (barely 70 mPa) sieving polymer solution, formed by short-chain (average mol wt
      of 230,000, 55,000 Mn) polyacrylamides; (c) substitution of four fragments in the
      classical multiplex reaction (181 and 535 bp in the Beggs, 416 and 459 bp in the
      Chamberlain) with four new fragments of different lengths (170, 313, 154 and 88
      bp, respectively). These new conditions allow resolution and unambiguous
      identification of all 18 PCR-amplified fragments in a single electrophoretic run.
      The set of 18 fragments comprises the following: 88, 113, 139, 154, 170, 196,
      202, 238, 268, 271, 313, 331, 357, 360, 388, 410, 506 and 547 bp.

PMID- 8527148
TI  - Large-scale genomic sequencing: optimization of genomic chemical sequencing
      reactions.
AB  - We have developed a streamlined, reproducible method for performing genomic
      chemical sequencing reactions on the genomic DNA of Mycoplasma capricolum, which
      has a genome size of about 750,000 base pairs and whose composition is 75% AT.
      The general modifications that ensure reproducibility and allow the processing of
      multiple samples can be widely adopted to other large-scale sequencing projects,
      while the specific modifications to the chemical reactions are applicable to the
      sequencing of other DNAs with a high AT content.

PMID- 8527149
TI  - Mutagenesis using trinucleotide beta-cyanoethyl phosphoramidites.
AB  - There is no easy way to selectively introduce mixtures of codon triplets into
      mutagenesis libraries. Solid-phase-supported DNA synthesis using successive
      coupling of mixtures of mononucleotides can be made to supply 32 codons, which
      gives redundancies in coding for 20 natural amino acids, as well as an often
      unwanted stop codon. Resin-splitting methods have been described, but the
      representation of all permutations is limited by mechanical factors for a large
      library, and the method is experimentally cumbersome. To demonstrate a third,
      improved method, the 3'-cyanoethyl phosphoramidite codon triplets dATA, dCTT,
      dATC, dATG and dAGC were made by solution-phase methods, with protecting groups
      fully compatible with modern automated phosphoramidite DNA synthesis chemistry.
      The reagents were then used to synthesize a 54-mer DNA fragment, wherein 15
      internal base pairs were randomized by coupling a mixture of the five codons five
      times. The fragment was amplified as a cDNA pool, which was subcloned into a
      phagemid vector, and 16 randomly selected recombinants from this mini-library
      were sequenced. These clones showed random incorporation of the proper
      transcribed codon sequences at the correct location. Other functional tests
      involving the trinucleotide phosphoramidites showed modest (ca. 70%) coupling
      efficiencies and structural integrity of the DNA produced.

PMID- 8527150
TI  - Use of Multiscreen plates for the preparation of bacterial DNA suitable for PCR.
AB  - A rapid and inexpensive method for isolating bacterial DNA for use in PCR is
      described. The method is based on the guanidinium thiocyanate (GuSCN)-lysis
      method of Boom et al. (J. Clin. Microbiol. 28:495-503, 1990) and enables a
      multiple of 96 samples to be prepared in only one hour. We use Multiscreen plates
      and a vacuum manifold from Millipore. Clinical samples are lysed and washed in
      the wells of a Multiscreen plate, and DNA is eluted in a standard microplate.
      Purified DNA was recovered with high yields (over 25%). The method allows
      multichannel or robotic pipetting for both the sample preparation as well as for
      the PCR step. The method has been applied successfully to detect pathogenic
      Streptococcus suis type 2 in nasal and tonsil swab specimens of pigs.

PMID- 8527151
TI  - Detection of nucleic acids in the attomole range using polybiotinylated
      oligonucleotide probes.
AB  - This article describes the optimization of the hybridization signal obtained with
      biotinylated oligonucleotides. Optimal number and positions of biotin moieties on
      a 33-base oligonucleotide probe were determined. The quality of avidin-peroxidase
      conjugate and the choice of chromogenic substrate influenced detection
      sensitivity. A signal amplification method was also developed for avidin
      enzymatic conjugates. These improvements allowed the detection of less than 0.02
      fmol of target DNA.

PMID- 8527152
TI  - Novel steroid derivative modulates gene expression of cytokines and growth
      regulators.
AB  - Topical steroid treatment is a common therapy for psoriasis. Steroids are known
      to bind to specific cytoplasmic receptors and to influence gene expression. We
      investigated the effects of the novel steroid derivative mometasone furoate on
      the expression of putative target genes in normal human epidermal cells (KC).
      Gene expression was measured by semiquantitative mRNA-PCR. In addition, cytokine
      receptor characteristics were assessed by ligand binding studies. We found a dose
      dependent downregulation of proinflammatory mediators (IL-8, TNF alpha). Genes
      involved in growth regulation (HER-2, p53) were also modulated. IL-8 binding to
      KC was inhibited. We conclude that modulation of the expression of cytokine,
      cytokine receptor and growth factor genes may contribute to the antipsoriatic
      action of steroids.

PMID- 8527153
TI  - The penetration enhancer SEPA augments stimulation of scalp hair growth by
      topical minoxidil in the balding stumptail macaque.
AB  - The purpose of this study was to determine if the penetration enhancer SEPA (2-n
      nonyl-1,3-dioxolane) would augment the scalp hair growth effects of topical
      minoxidil in the balding stumptail macaque. A 1-in2 area on the balding scalp of
      40 adult female monkeys (four drug-treated and four vehicle-treated groups of 5
      monkeys each) was topically treated 5 days/week, q.d. or b.i.d., with
      approximately 250 microliters of minoxidil-SEPA (2.5% minoxidil, weight/volume in
      10% SEPA, 25% propylene glycol and 65% isopropyl alcohol), Rogaine topical
      solution (TS, 2% minoxidil, weight/volume in 20% propylene glycol, 60% ethanol
      and 20% water) or respective vehicles (without drug) for 16 weeks via paintbrush
      application. Scalp hair was collected by shaving and vacuuming the dosed area at
      baseline and at 4-week intervals. The shaved hair was filtered, weighed and
      recorded as the change from baseline. The q.d. and b.i.d. minoxidil-SEPA groups
      displayed a significant increase in hair weight compared to their respective
      vehicles at week 4 whereas q.d. and b.i.d. Rogaine TS groups were not active
      until week 8 and 12, respectively. Both minoxidil-SEPA treatments produced
      significantly greater cumulative hair weight over the entire 16-week study
      compared to either of the Rogaine TS treatments. Comparable increases in
      cumulative hair weight were evident between q.d. and b.i.d. minoxidil-SEPA groups
      and between q.d. and b.i.d. Rogaine TS groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527154
TI  - Noninvasive investigation of human skin after in vivo iontophoresis.
AB  - The main objective of our study was to investigate skin function and structure in
      human volunteers after electrical current application in order to demonstrate the
      safety of iontophoresis in vivo. The direct current was applied for 30 min at a
      density of 0.1 and 0.2 mA/cm2. Iontophoresis increased cutaneous blood flow as
      measured by laser Doppler flowmetry (LDF). This increase was reversible within 1
      h and was more pronounced at higher current density. Measurements of
      transepidermal water loss (TEWL) and LDF were the same at the cathode and the
      anode sites. Except for 5 min at 0.2 mA/cm2 density, TEWL values were not
      enhanced as compared to control values (no iontophoresis). Attenuated total
      reflectance-Fourier transform infrared spectroscopy of the stratum corneum
      structure showed a transient increase (30 min) in hydration after electrode
      application for 30 min. No alteration in lipid structure could be shown. These
      results augur the safety of drug delivery by iontophoresis.

PMID- 8527155
TI  - Electrical methods for skin moisture assessment.
AB  - Skin sites on 8 test subjects were treated with moisturizers, and different
      electrical measuring methods were compared regarding their quality in the
      assessment of the induced changes in the stratum corneum hydration level. Low
      frequency susceptance measurements were found preferable to high frequency
      admittance measurements, and the advantages of monopolar measurements with the
      three-electrode system are described.

PMID- 8527156
TI  - Skin surface lipid and skin friction: relation to age, sex and anatomical region.
AB  - Differences in the skin surface lipid content (SSL) and the dynamic friction
      coefficient (mu) were investigated with respect to age, sex, and anatomical
      region in 29 volunteers. The group consisted of (a) 7 young adult females (24.9
      +/- 1.1 years old, mean +/- SD), (b) 7 old females (75.3 +/- 2.4 years old), (c)
      7 young adult males (28.7 +/- 0.5 years old), and (d) 8 old males (73.8 +/- 1.9
      years old). Measurements were obtained on 11 anatomical regions, namely, the
      forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen,
      upper and lower back, thigh, and ankle. Skin surface lipid content data were
      compared with mu measurements to determine the relative contribution of the
      former to frictional properties of skin. mu and SSL were not statistically
      different between age groups on all regions except for the ankle, where lipid
      content was lower in the elderly. Similarly, mu did not vary between sex groups.
      Skin surface lipid content was statistically lower on the forehead, dorsal
      forearm and postauricular area in females. Both parameters, however, showed
      considerable regional variability. A significant linear correlation was
      established between mu and SSL combining all regions from all volunteers. When mu
      was plotted against SSL among individual anatomic sites, only the forehead and
      postauricular area showed significant linear correlations between the two
      parameters. These data suggest that surface lipid content plays a limited role in
      frictional properties of skin.

PMID- 8527157
TI  - Texture analysis of the surface of the human skin.
AB  - The roughness parameters known from surface engineering often used to describe
      the microtopography of the surface of the skin do not, by definition, take into
      account the two-dimensional relationships of the stratum corneum. An approximate
      description of these relationships can be obtained by scanning several radial
      profile sections. A more detailed analysis of the characteristic surface relief
      of the skin can also be based on the texture parameters used to characterize many
      natural structures. These types of parameters can be extracted from the gray
      level images of an impression of the surface of the skin--a replica--that has
      been magnified under a microscope, photographed with a CCD camera and
      subsequently subjected to image analysis by a digital computer. The purpose of
      this study is to determine not only the usefulness of texture parameters for
      describing the morphology of the surface of the human skin but also whether, for
      example, cosmetically treated skin can be detected by means of texture analysis.

PMID- 8527158
TI  - Interactions between the Flk-1 receptor, vascular endothelial growth factor, and
      cell surface proteoglycan identified with a soluble receptor reagent.
AB  - Fetal liver kinase-1 (Flk-1) is a transmembrane tyrosine kinase that was
      identified in endothelial cells and populations of cells enriched in
      hematopoietic progenitors. To characterize the interaction of Flk-1 with
      potential ligands the receptor extracellular domain was genetically fused to an
      alkaline phosphatase (AP) tag. A soluble ligand for Flk-1 was identified in the
      supernatants of numerous mesenchymal cell lines by co-immunoprecipitation with
      the Flk1-AP fusion protein. This polypeptide was shown by N-terminal sequencing
      to be vascular endothelial growth factor (VEGF). Receptor-AP fusion proteins can
      thus be used to identify soluble ligands as well as transmembrane ligands, and
      this approach is therefore likely to be widely applicable to many types of orphan
      receptor. The Flk1-AP soluble receptor was also found to bind to cell surfaces,
      showing two apparent classes of binding site with different affinities. This
      interaction could be reconstructed by introducing a VEGF expression plasmid into
      cells. These results indicate that VEGF presented at the cell surface can bind to
      the Flk-1 receptor, and could mediate a direct cell-cell interaction. The Flk1-AP
      fusion protein was also found to bind heparin, implying that ligand binding by
      the Flk-1 receptor may involve a three way interaction between the Flk-1
      receptor, VEGF, and heparin-like cell surface proteoglycans.

PMID- 8527159
TI  - Differential expression of vascular endothelial growth factor (vascular
      permeability factor) forms in rat tissues.
AB  - Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF),
      exists as multiple forms due to alternative splicing of mRNA. VEGF165/164
      (human/rodent homologue) is often assumed to be the predominant form, although
      truly quantitative assessments are lacking. We have used the RNase protection
      assay to directly quantitate the relative abundance of VEGF mRNA forms in five
      rat tissues (brain, kidney, lung, spleen, and heart) and two rat glioma cell
      lines (C6 and 9L). The three major forms, which code for proteins of 188, 164,
      and 120 amino acids, were observed in all of the tissues and cells examined.
      However, the relative abundance differed among the samples. VEGF188 was the
      predominant form (> 50% of total VEGF mRNA) in heart and lung, but was the least
      abundant form (6-15%) in all other samples. VEGF164 was lower (approximately 25%)
      in heart and lung, but was predominant (> 50%) in brain and kidney. VEGF164 and
      VEGF120 were present in equimolar amounts (each form approximately 46% of total)
      in the spleen, C6, and 9L. VEGF120 was also present in kidney (38%) and lung
      (27%) and was least abundant (approximately 15%) in brain and heart. A rat
      homologue of VEGF206 was not observed. VEGF mRNA splicing occurs in a tissue
      specific manner. The assumption that the predominant physiologic form of VEGF is
      a VEGF165/164 homodimer should be viewed with caution.

PMID- 8527160
TI  - Expression of biologically active human vascular endothelial growth factor in
      yeast.
AB  - Vascular endothelial growth factor (VEGF) is a glycoprotein consisting of two
      identical polypeptide chains linked by a disulfide bond. The unique biological
      activities of VEGF include its potent mitogenic and permeability inducing
      properties specific for the vascular endothelium. VEGF is implicated in tumor
      angiogenesis, wound healing, and the stimulation of collateral vessel formation
      at the site of arterial occlusion. Therefore, in order to produce large
      quantities of biologically active VEGF, a splice variant (VEGF165) was cloned and
      expressed in a yeast expression system. The coding region of VEGF165 was isolated
      from U937 cells by RT-PCR, sequenced and then cloned into the yeast expression
      vector pHILS1. VEGF165 was secreted into the medium as a dimer. Recombinant VEGF
      reacted to antibodies raised against the N-terminal and C-terminal synthetic
      polypeptides of human VEGF. As much as 35-40 mg/L of purified VEGF could be
      obtained from the yeast expression system. The recombinant protein was
      biologically active in inducing vascular endothelial cell proliferation in vitro
      and permeability changes in vivo.

PMID- 8527161
TI  - Effects of oxygen on wound responses to growth factors: Kaposi's FGF, but not
      basic FGF stimulates repair in ischemic wounds.
AB  - Kaposi's fibroblast growth factor (K-FGF, FGF-4) is a newer member of FGF family
      with uncharacterized wound healing properties. Basic fibroblast growth factor
      (bFGF, FGF-2) has been well studied and accelerates repair in normal and impaired
      wound healing models. K-FGF and bFGF are known to have similar biological effects
      in tissue culture, and both stimulate fibroblast and endothelial cell
      proliferation. The rabbit dermal ulcer model was used to examine the effects of
      bFGF and K-FGF under ischemic and nonischemic conditions. We found bFGF was
      ineffective in stimulating healing under ischemic conditions even at high doses
      (30 micrograms/wound). However, when the ischemic wounds were treated with bFGF
      (5 micrograms/wound) plus hyperbaric oxygen therapy, it was highly effective
      again as previously found under nonischemic conditions (P < 0.05). In contrast K
      FGF stimulated repair in both nonischemic and ischemic wounds (P < 0.05). These
      results suggest that wound oxygen content differentially regulates responsiveness
      to bFGF and that K-FGF is biologically active in hypoxic wounds.

PMID- 8527162
TI  - FGF-1 but not FGF-4 secreted by carcinoma cells promotes in vitro and in vivo
      angiogenesis and rapid tumor proliferation.
AB  - The progressive growth of solid tumors is dependent on the tumor ability to
      recruit new blood vessels from the surrounding host tissues. We show here that
      acidic Fibroblast Growth Factor (FGF-1) produced by a rat bladder carcinoma
      transfected cell line (NBT-II cells) is a potent inducer of angiogenesis. After
      injection in nude mice, NBT-II cells transfected with FGF-1 form rapidly growing
      carcinomas which are highly vascularized, whereas carcinoma cells producing a
      biologically active form of FGF-4 behave like non-producer cells. The vasculature
      of the tumors obtained with NBT-II cells producing a secreted form of FGF-1 is
      dramatically expanded but lacking in some places a complete endothelial lining.
      Conditioned medium from these cells induce formation of capillary-like structures
      in vitro, whereas those of FGF-4 and non-secreting FGF-1 producing cells failed
      to induce such structures. Our results indicate that the expression of FGF-1 may
      promote tumor growth, at least in part, by inducing angiogenesis, and that the
      acquired ability of tumor cells to secrete FGF-1 but not FGF-4, may result in
      aberrant neovascularization of the tumor.

PMID- 8527163
TI  - BK1: an FGF-responsive central nervous system-derived cell line.
AB  - Fibroblast growth factors (FGF) are expressed at high levels in the central
      nervous system (CNS), however their function in the CNS is not well understood.
      The immortalized neuronal cell line (BK1), derived from a transgenic mouse
      central nervous system tumor, expresses high levels of FGF receptor 1 (FGFR1) and
      demonstrates both morphologic and biochemical changes when treated with basic FGF
      (FGF-2). We have derived subclones of BK1 cells with varying degrees of FGF
      responsiveness by transfecting either a wild type (FRW) or a truncated (FRX) form
      of FGFR1. Cells expressing high levels of FGFR1 rapidly and uniformly respond to
      FGF, while cells expressing FRX fail to respond to FGF, either morphologically or
      by the expression of molecular markers. These BK1 subclones will prove useful to
      study FGFR mediated signal transduction and FGFR responsive genes in a CNS
      derived cell. These studies also demonstrate that a dominant negative FGF
      receptor can be used as a tool to elucidate the function of FGF in the central
      nervous system.

PMID- 8527164
TI  - Stem cell factor induces phosphorylation of a 200 kDa protein which associates
      with c-kit.
AB  - Stem cell factor (SCF) promotes limited proliferation and differentiation of
      hematopoietic progenitor cells and is potently synergistic in combination with
      growth factors such as granulocyte-macrophage colony stimulating factor (GM-CSF),
      interleukin 3 (IL-3) or erythropoietin (Epo). We have examined tyrosine
      phosphorylation induced by SCF in the megakaryoblastic cell line Mo7e and found
      phosphorylation of proteins of 200, 145, 120, 58 and 55 kDa. The dominant
      phosphotyrosylproteins in SCF treated cells were 200 and 145 kDa. Our studies
      indicated that the 145 kDa protein was c-kit, the receptor for SCF. Subsequent
      work was directed towards further characterizing the 200 kDa protein. Surface
      labeling of Mo7e cells suggested that p200 had an extracellular domain and could
      be induced to associate with c-kit after stimulation with SCF. The rapid
      phosphorylation of p200 and its immediate association with c-kit suggest that
      p200 is potentially a component of the SCF signal transduction pathway.

PMID- 8527165
TI  - A potent human interleukin-4 antagonist stimulates the proliferation of murine
      cells expressing the human interleukin-4 binding chain.
AB  - A single-amino-acid substitution mutant form of human interleukin-4 (hIL-4),
      Y124D.hIL-4, has been described previously as an antagonist of the effects of hIL
      4 on various human cells. The murine T-cell leukemic cell line CT.h4S, which
      expresses the human IL-4 receptor, proliferates in response to both hIL-4 and
      murine IL-4. Although Y124D.hIL-4 antagonizes the proliferative effects of hIL-4
      on human phytohaemagglutinin-stimulated peripheral blood mononuclear cells,
      Y124D.hIL-4 is a potent stimulator for CT.h4S cells. Molecular modelling studies
      were performed to investigate the stability of different conformations of residue
      124 as well as the efficiency of different molecular mechanics force fields in
      homology modelling. We suggest that the aspartate substitution alters the C
      terminal end of the D-helix in such way that the analogue still binds to the
      human IL-4 receptor alpha-chain and signals through the murine gamma c-chain. In
      contrast, the Y124D.hIL-4/IL-4 receptor complex cannot signal through the human
      gamma c-chain.

PMID- 8527166
TI  - Polymorphic distribution and molecular diversification of mitochondrial plasmid
      like DNAs in the genus Oryza.
AB  - Four kinds of circular plasmid-like DNA, designated B1, B2, B3 and B4, have been
      found in the mitochondria of rice (Oryza sativa L.). We analyzed the distribution
      of families of plasmid-like DNAs homologous to those of O. sativa in 40 strains
      of the genus Oryza with AA, BB, BBCC, CC, CCDD and EE genomes. Plasmid-like DNAs
      were observed only strains having AA, CC and CCDD genomes. The distribution
      patterns of strains with AA genome were highly polymorphic. We amplified the
      plasmid-like DNAs from strains with the AA genome by PCR and examined restriction
      fragments length polymorphisms (RFLPs). RFLPs were detected among families of
      plasmid-like DNA amplified from different strains. This result indicated that
      some mutations, such as base substitutions and the insertion or deletion of a
      small fragment of DNA, had occurred and had accumulated during the
      differentiation of strains with an AA genome.

PMID- 8527167
TI  - CT of the lungs in patients with pulmonary emphysema.
AB  - Pulmonary emphysema is a pathological diagnosis. The clinical diagnosis of
      emphysema can be difficult because correlations between results of lung function
      tests and the extent of emphysema are poor. Features of chronic bronchitis or
      asthma may overlap with emphysema, making the clinical diagnosis more
      challenging. Nonetheless, the diagnosis of pulmonary emphysema can be made with
      relative confidence on the basis of clinical and radiological criteria. Despite
      not detecting mild emphysema and underestimating the severity of disease, CT--and
      high-resolution CT in particular--is the best noninvasive modality for detecting
      or corroborating pulmonary emphysema. This review focuses on several important
      aspects of pulmonary emphysema: (1) the definition and pathological
      characterization, (2) techniques of CT imaging, (3) CT findings and their
      correlation with pathophysiological data, and (4) quantification with CT.

PMID- 8527168
TI  - Acute lung disease in the immunocompromised host: differential diagnosis at high
      resolution CT.
AB  - The aim of this manuscript is to review the CT findings of pulmonary
      complications seen in acquired immunodeficiency syndrome (AIDS) and in non-AIDS
      immunocompromised patients. The most common pulmonary complications in patients
      with AIDS include infection, Kaposi's sarcoma, and AIDS-related lymphoma. The
      most common complications seen in non-AIDS immunocompromised patients include
      infection, drug-induced lung disease, diffuse pulmonary hemorrhage, and pulmonary
      edema.

PMID- 8527169
TI  - CT and pathological correlation of pulmonary sarcoidosis.
AB  - In CT the presence of mediastinal or hilar lymphadenopathies and thickened
      bronchovascular bundles are landmarks for the diagnosis of pulmonary sarcoidosis.
      The major CT findings for parenchymal involvement are thickened bronchovascular
      bundles, large parenchymal nodules, pleural or subpleural nodules, ground-glass
      opacities, local lung volume loss (distortion of the lung parenchyma), and
      microscopic and macroscopic honeycombing. The thickened bronchovascular bundles
      correspond histologically to granulomas, either with or without perigranulomatous
      fibrosis in the connective tissue sheath around the pulmonary vessels and
      airways. Conglomerate granulomas are represented on CT by high-attenuation
      nodules, and the ground-glass opacities are caused by the summation of a number
      of small granulomas in the interstitium.

PMID- 8527170
TI  - Role of thoracoscopy and preoperative localization procedures in the diagnosis
      and management of pulmonary pathology.
AB  - Video-assisted thoracic surgery is an important component of modern thoracic
      surgery, providing a safe, less invasive alternative to open thoracotomy in the
      evaluation of pleural, mediastinal, and parenchymal pathology. Advancements in
      endoscopic techniques and video-optics have permitted greater visualization of
      the thoracic cavity and allowed limited pulmonary resections with significantly
      reduced postoperative morbidity. Thoracoscopy is indicated for diagnosis of
      intrathoracic pathology when usual methods of diagnosis, including fine-needle
      aspiration and transbronchial biopsy, are inconclusive. The diagnostic accuracy
      of video-assisted thoracic surgery approaches 100%. Increasingly, the indications
      for thoracoscopy include therapeutic resections of pulmonary nodules in cases of
      limited lung metastases and bronchogenic carcinoma when pulmonary function is
      poor. Successful diagnostic and therapeutic resection by thoracoscopy requires
      intraoperative localization of the lesion within the collapsed lung. The
      indications and methods of thoracoscopic surgery and preoperative localization
      are discussed.

PMID- 8527171
TI  - CT of pulmonary metastases with pathological correlation.
AB  - CT, including high-resolution CT, has become an essential means of imaging to
      evaluate pulmonary metastases. The underlying pathological processes of pulmonary
      metastases can be observed well on CT images, but they are not always specific.
      Several important CT features correlate with histopathological findings: (1)
      margin of nodule; (2) hemorrhage accompanying a metastatic nodule; (3)
      calcification; (4) cavitation; (5) sterilized metastasis; (6) small metastatic
      nodules in the lobules; (7) lymphangitic carcinomatosis; (8) tumor emboli; and
      (9) pleural metastases. For reasonable use of CT in pulmonary metastases, these
      various CT manifestations and their limitations must be understood.

PMID- 8527172
TI  - Bronchiectasis: CT/clinical correlations.
AB  - The association between bronchiectasis and human immunodeficiency virus
      infection, the resurgence of tuberculosis, especially in urban and
      immunocompromised patients, and the recognition of bronchiectasis as a
      manifestation of rejection in the transplant population are emerging clinical
      settings in which establishing the diagnosis of bronchiectasis is becoming
      increasingly important. High-resolution CT, by virtue of its well-established
      accuracy, is currently accepted as the optimal noninvasive means of diagnosing
      bronchiectasis. However, reliable diagnosis requires meticulous attention to
      technique and a thorough knowledge of potential pitfalls. These include, among
      others, respiratory and cardiac motion artifacts as well as effects of
      collimation and electronic windowing. It also is important to recognize diseases
      that may mimic the appearance of bronchiectasis as well as unusual manifestations
      of bronchiectasis that may obscure the diagnosis.

PMID- 8527173
TI  - CT of pulmonary tuberculosis.
AB  - CT scans in patients with primary tuberculosis commonly show lymphohematogenous
      spread of the disease, whereas those of postprimary (reactivation) tuberculosis
      commonly show bronchogenic spread. High-resolution CT (HCRT) is extremely helpful
      in understanding pathomorphological changes, mode of spread of the disease, and
      sequential morphological change after antituberculous chemotherapy, and possibly
      in diagnosing activity of the disease. Centrilobular 2- to 4-mm nodules or
      branching linear lesions representing intrabronchiolar and peribronchiolar
      caseation necrosis are the most common findings of early bronchogenic spread of
      tuberculosis. The 2- to 4-mm centrilobular nodules may coalesce to form 5- to 8
      mm nodules or lobular consolidation. Cavitation usually begins at the central
      portion of a lobule around the bronchioles. Resolution of the tuberculous lesions
      occurs with antituberculous chemotherapy, resulting in varying degrees of
      fibrosis, bronchovascular distortion, emphysema, and bronchiectasis. HRCT may
      show both paracicatricial irregular emphysema and lobular emphysema. CT findings
      of early miliary dissemination commonly include ground-glass opacification with
      barely discernible nodules that show discrete miliary nodules thereafter. CT also
      is useful in the evaluation of long-standing destructive pulmonary lesions and
      tracheobronchial tuberculosis.

PMID- 8527174
TI  - Identification and evaluation of centrilobular opacities on high-resolution CT.
AB  - Abnormal findings on high-resolution CT that are localized to the centrilobular
      region imply primary disease of the small airways or primary peribronchiolar or
      perivascular pathology. We review methods of localizing abnormal opacity to the
      centrilobular region and discuss differential diagnostic considerations for
      centrilobular disease. Straightforward ways to differentiate between primary
      small-airways disease and peribronchiolar or perivascular conditions are also
      emphasized. Although perilymphatic disorders can also be associated with
      centrilobular opacities, these conditions have a distinctive appearance that
      warrants separate categorization; distinguishing characteristics of perilymphatic
      disorders with respect to the centrilobular conditions are discussed.

PMID- 8527175
TI  - The pursuit of research publications.

PMID- 8527176
TI  - Looking after health: the Basque health care reform.

PMID- 8527177
TI  - Bovine spongiform encephalopathy and the public health.

PMID- 8527178
TI  - The cost of treating hip fractures in the twenty-first century.

PMID- 8527179
TI  - Improving the coverage and quality of cervical screening: women's views.

PMID- 8527180
TI  - Prevalence of risk factors for sudden infant death syndrome in south east England
      before the 1991 national 'Back to Sleep' health education campaign.

PMID- 8527181
TI  - The impact of ageing upon the need for medical beds: a Monte-Carlo simulation.

PMID- 8527182
TI  - Occupational and environmental links to mesothelioma deaths occurring in Leeds
      during 1971-1987.

PMID- 8527183
TI  - A pilot study of the use of clinical guidelines to determine appropriateness of
      patient placement on intensive and high dependency care unit.

PMID- 8527184
TI  - Clinical audit of forefoot surgery performed by registered medical practitioners
      and podiatrists.

PMID- 8527185
TI  - Primary care and the public health: general practitioners and health protection.

PMID- 8527186
TI  - GP fundholding and the costs of prescribing.

PMID- 8527187
TI  - On the need for evidence-based medicine.

PMID- 8527188
TI  - Human rights and medical practice, including reference to the joint Oslo
      statements of September 1993 and March 1994.

PMID- 8527189
TI  - Knowledge, attitude and behaviour of TB patients.

PMID- 8527190
TI  - Healthcare resource groups--version 2.

PMID- 8527191
TI  - Quarterly communicable disease review January to March 1995. From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 8527192
TI  - Abdominal obesity and glucose intolerance in middle-aged women in the United Arab
      Emirates.

PMID- 8527194
TI  - The new requirements for communicable disease training.

PMID- 8527193
TI  - Is hospital the right place.

PMID- 8527195
TI  - The new requirements for communicable disease training.

PMID- 8527196
TI  - Removing intrinsic stains from vital teeth by microabrasion and bleaching.

PMID- 8527197
TI  - Optimizing Class II composite resin esthetic restorations by the use of ceramic
      inserts.

PMID- 8527198
TI  - Clinical application of custom machined angled abutments.

PMID- 8527199
TI  - Developing optimal peri-implant papillae within the esthetic zone: guided soft
      tissue augmentation.

PMID- 8527200
TI  - Effect of pH on hydrogen peroxide bleaching agents.

PMID- 8527201
TI  - Intraoral television and the emerging office electronic network.

PMID- 8527202
TI  - Dental ceramics: yes, there is a difference "over there".

PMID- 8527203
TI  - Esthetic pontic receptor site development: a histologic study in rats.

PMID- 8527204
TI  - The contact lens effect: enhancing porcelain veneer esthetics.

PMID- 8527205
TI  - Are you afraid to refer?

PMID- 8527206
TI  - New dental ceramics and esthetics.

PMID- 8527207
TI  - Implants for tooth movement: a fabrication and placement technique for
      provisional restorations.

PMID- 8527208
TI  - Esthetics in the cracked tooth syndrome: steps to success using resin-bonded
      ceramic restorations.

PMID- 8527209
TI  - Posterior direct resin-bonded restorations: still an esthetic alternative.

PMID- 8527210
TI  - Split-shank threaded posts and threaded posts: tensile properties and stress
      levels.

PMID- 8527211
TI  - Increase case acceptance with effective communication skills.

PMID- 8527212
TI  - The evolution of national nutrition policy.
AB  - Domestic regulatory efforts in the area of nutrition historically have focused on
      achieving and sustaining the highest possible level of food safety and
      availability. More recently, the linkages between certain dietary practices and
      the risk of chronic, degenerative diseases have also become a significant focus
      of public policy. In order to promote good nutrition practices, the Food and Drug
      Administration (FDA) now requires a detailed and informative Nutrition Facts food
      label on virtually all food packages. Other public policies promoted by the FDA
      and others include increasing public knowledge of the relationship between diet
      and health; promoting unified food and nutrition policies among all government
      agencies; educating the American consumer about sound dietary practices; and
      encouraging the development of technologies that may result in more healthful,
      more abundant, and more affordable foods.

PMID- 8527213
TI  - Role of vitamin K in bone metabolism.
AB  - Vitamin K is a cofactor required for the formation of gamma-carboxyglutamate
      (Gla) residues in proteins. Osteoblasts produce at least three different Gla
      containing proteins: osteocalcin, matrix Gla-protein, and protein S. After
      cellular secretion of these proteins, the main part of each remains bound to the
      hydroxyapatite matrix in bone, but their function remains unclear. Part of the
      newly synthesized osteocalcin is also set free into the bloodstream, where it may
      be used as a diagnostic marker for bone formation. Several studies have
      demonstrated that a poor vitamin K status is associated with an increased risk of
      osteoporotic bone fractures. Whether vitamin K supplementation will reduce the
      rate of bone loss in postmenopausal women remains a matter of debate.

PMID- 8527214
TI  - Retinoids as teratogens.
AB  - Vitamin A is a necessary nutrient in the diet. However, excessive doses of
      retinoids by pregnant women result in teratogenesis. In this chapter, we
      initially discuss the occurrence and characteristics of fetal malformations
      associated with maternal ingestion of natural and synthetic retinoids in both
      experimental animals and humans. We then turn to an examination of the
      pharmacology of teratogenic retinoids, focusing on structure-function
      relationships and pharmacokinetics. Finally, we review the current literature on
      the molecular mechanism of action of teratogenic doses of retinoids and the role
      of the retinoic acid receptors and other target genes in this process.

PMID- 8527215
TI  - Regulation of glutaminase activity and glutamine metabolism.
AB  - Glutamine is synthesized primarily in skeletal muscle, lungs, and adipose tissue.
      Plasma glutamine plays an important role as a carrier of nitrogen, carbon, and
      energy between organs and is used for hepatic urea synthesis, for renal
      ammoniagenesis, for gluconeogenesis in both liver and kidney, and as a major
      respiratory fuel for many cells. The catabolism of glutamine is initiated by
      either of two isoforms of the mitochondrial glutaminase. Liver-type glutaminase
      is expressed only in periportal hepatocytes of the postnatal liver, where it
      effectively couples ammonia production with urea synthesis. Kidney-type
      glutaminase is abundant in kidney, brain, intestine, fetal liver, lymphocytes,
      and transformed cells, where the resulting ammonia is released without further
      metabolism. The two isoenzymes have different structural and kinetic properties
      that contribute to their function and short-term regulation. Although there is a
      high degree of identity in amino acid sequences, the two glutaminases are the
      products of different but related genes. The two isoenzymes are also subject to
      long-term regulation. Hepatic glutaminase is increased during starvation,
      diabetes, and feeding a high-protein diet, whereas kidney-type glutaminase is
      increased only in kidney in response to metabolic acidosis. The adaptations in
      hepatic glutaminase are mediated by changes in the rate of transcription, whereas
      kidney-type glutaminase is regulated at a posttranscriptional level.

PMID- 8527216
TI  - Roles of ubiquitinylation in proteolysis and cellular regulation.
AB  - Most eukaryotic organisms respond to starvation, nutrient deprivation, and/or
      stress by increasing the rates of intracellular proteolysis. The amino acids
      released may be reutilized for synthesis of important proteins, or directly for
      the production of energy. This enhanced proteolysis is also required for repair
      of cellular damage due to environmental insults such as heat shock, free
      radicals, viral infection, or mutation. Finally, intracellular proteolysis is
      important in determining the steady-state levels of a wide variety of regulatory
      proteins, particularly those regulating the cell cycle. The ubiquitin-dependent
      proteolytic system participates in all of these functions. In spite of its
      cytoplasmic localization, this system is selective and acts only on a limited set
      of substrates. This review discusses the mechanisms of this selectivity and the
      potential roles of ubiquitin-dependent proteolysis.

PMID- 8527217
TI  - Energy partitioning and modeling in animal nutrition.
AB  - We first present a brief discussion of early and current models (feeding systems)
      used to estimate animal energy and protein requirements and to predict
      performance based on feed composition and intake. We then touch on some
      limitations inherent in these systems. Next, we propose that dynamic (i.e. time
      variant) models and mechanistic models (i.e. equations based on knowledge of
      physiological functions) are superior to earlier systems for both practical and
      research applications. Finally, we describe a number of applied and research
      models of animal growth and lactation to illustrate how biological concepts may
      be represented in equation form. Equations that represent current knowledge of
      underlying functions can be used to improve predictions of animal requirements
      and performance and to evaluate hypotheses about nutritional and physiological
      mechanisms that influence animal performance.

PMID- 8527218
TI  - Regulation of pigeon cropmilk secretion and parental behaviors by prolactin.
AB  - Prolactin stimulates the growth and development of specialized epithelial cells
      lining the cropsac of pigeons and doves (family Columbidae), leading to formation
      of "cropmilk," which is fed to the newly hatched squab. This system of milk
      feeding is unique among birds. To support the feeding of cropmilk, a complex
      array of behavioral adaptations are also supported by high levels of prolactin
      secretion in columbids during parenting. These specializations include elevated
      food intake (hyperphagia), nest attendance, and regurgitation feeding of the
      squab. Although prolactin is clearly important for these behavioral adaptations,
      the precise physiological and mechanistic bases for these behavioral effects
      remain controversial. The molecular mechanisms of prolactin action in the cropsac
      epithelium have been studied by cloning prolactin-induced genes, by cloning and
      expressing the pigeon prolactin receptor, and by analyzing the transcription
      factors that are activated after prolactin treatment. The avian (pigeon)
      prolactin receptor is a member of the cytokine receptor superfamily and uniquely
      contains a complete duplication of the extracellular ligand-binding domain. One
      of the early signal-transducing actions of prolactin in cropsac epithelium is the
      activation of signal transducer and activator of transcription (STAT) proteins
      via tyrosine phosphorylation. This fundamental signaling pathway is shared with
      mammalian prolactin target tissues. The convergent evolution of milk feeding and
      the behaviors that support parenting in columbids and mammals has depended on
      adaptation of both conserved mechanisms and divergent physiological processes.

PMID- 8527219
TI  - The hypobetalipoproteinemias.
AB  - The fifth- and ninety-fifth-percentile concentrations of low-density lipoprotein
      (LDL) cholesterol in most Western populations are approximately 90 and 200 mg/dl,
      respectively. Persons with LDL cholesterol levels equal to or less than the fifth
      percentile are defined as having hypobetalipoproteinemia. Epidemiologic studies
      show that such individuals have lower-than-average risk for atherosclerotic
      cardiovascular disease but higher risk for a variety of cancers, pulmonary, and
      gastrointestinal diseases than persons with higher levels of cholesterol. The
      reasons for this are not known, nor are the causes of most cases of
      hypobetalipoproteinemia. However, in some well-studied kindreds the
      hypobetalipoproteinemia phenotype is inherited as an autosomal dominant trait.
      Heterozygotes in such kindreds are usually healthy and have no difficulty
      absorbing dietary fat. In most kindreds, the molecular variants responsible for
      the hypobetalipoproteinemia are unknown, but a subset of kindreds have strong
      genetic linkages between the low-cholesterol phenotype and truncation-producing
      mutations of the apolipoprotein (apo) B-100 gene. The truncations of apoB are
      named according to a centile nomenclature. The full-length 4536-amino acid
      protein is called apoB-100, and the 25 truncations identified to date have been
      named apoB-2 to apoB-89. The mutations introduce premature termination codons
      resulting from frameshift-producing base additions or deletions. The mutations
      produce slowed rates of secretion of the truncated apoBs relative to the apoB
      100s present in the heterozygotes. In addition, the apoB-100 molecules of the
      heterozygotes are also secreted at rates slower than those observed in closely
      matched normolipidemic controls. These physiologic results account for the
      hypobetalipoproteinemia of these subjects. The response of the plasma
      lipoproteins of heterozygotes to the manipulation of various dietary components
      remains to be determined. Additional low-cholesterol syndromes are autosomal
      recessive forms of hypobetalipoproteinemia, chylomicron retention disease, and
      abetalipoproteinemia. The molecular causes of the first two are unknown.
      Abetalipoproteinemia is an autosomal recessive condition resulting from mutations
      of the microsomal triglyceride transfer protein. All three conditions are
      characterized by vanishingly small concentrations of LDL, dietary fat
      malabsorption, and failure to thrive in infancy.

PMID- 8527220
TI  - Regulation of iron metabolism: translational effects mediated by iron, heme, and
      cytokines.
AB  - Recent advances in the knowledge of iron metabolism underscore its complex
      relationship to overall cell metabolism. One of the key components of the iron
      uptake and storage pathway is ferritin, a protein that sequesters iron in a
      nontoxic form. Ferritin synthesis is translationally regulated by iron. Molecules
      such as nitric oxide and cytokines also affect transcriptional and/or
      posttranscriptional ferritin synthesis. Conversely, iron-containing molecules
      affect expression of mitochondrial aconitase, erythroid aminolevulinic acid
      synthase, and nitric oxide synthase. This observation indicates a complex linkage
      between iron metabolism and a variety of other important cell activities. The
      finding that the cytoplasmic iron-responsive protein (IRP) has two forms also
      raises intriguing questions about the relationship between the cytoplasmic
      aconitase and translational regulation of mRNAs such as ferritin. At least one of
      the IRPs can be phosphorylated. These recent discoveries open exciting new
      avenues for research that should lead to a better understanding of cellular iron
      metabolism.

PMID- 8527221
TI  - Thermogenesis and thyroid function.
AB  - The past 10 years have seen tremendous progress in the definition of the nuclear
      mechanism of action of thyroid hormones. Although the way in which these nuclear
      mechanisms underlie the 3,5,3'-triiodo-L-thyronine (T3)-dependent stimulation of
      metabolic rate remains to be clarified, evidence favoring non-nuclear pathways is
      limited. Clearly, T3 stimulates both the production and consumption of energy
      within cells. It also exerts a number of parallel effects that result in
      increased oxygen consumption, e.g. on mitochondrial structure and composition; on
      the metabolism of lipids, carbohydrates, and proteins, and on cardiac function.
      Additionally, T3 may increase the proton permeability of the inner mitochondrial
      membrane, which implies that it may decrease the efficiency of energy production.
      These metabolic effects of T3 appear to be restricted to homeothermic-animals,
      representing a coordinated response to the challenge of maintaining body
      temperature.

PMID- 8527222
TI  - Cellular copper transport.
AB  - Cellular copper transport processes are required by all organisms for correct
      utilization in cell biochemical processes and avoidance of the toxicity of copper
      excess. Copper import into bacterial, yeast, and mammalian cells requires the
      coordinate function of proteins with both metal-binding and catalytic domains in
      mediated transport steps. Following entry, detoxification mechanisms found across
      species include the binding of copper to specific proteins (e.g.
      metallothioneins) and the transfer of copper into isolated cell compartments
      (e.g. periplasmic space, lysosome). Multiple proteins mediate intracellular
      transfers in bacteria, and glutathione may play a major role in cytosolic copper
      delivery to cuproenzymes in mammalian cells. Study of two human disorders of
      copper transport, Menkes disease and Wilson disease, led to the identification of
      an important category of proteins mediating cell copper export. The Menkes and
      Wilson disease gene products are copper-transporting ATPases of the P type, with
      ATPase domains and N-terminal metal-binding amino acid motifs that are
      evolutionarily conserved in unicellular and mammalian organisms. These
      observations suggest that yeast and bacterial copper transport proteins, or
      individual domains of these proteins, may generally have homologues in mammalian
      systems.

PMID- 8527223
TI  - Nutritional and hormonal regulation of thyroid hormone deiodinases.
AB  - Selenocysteine has been identified in the active center of types 1 and 3
      iodothyronine deiodinases, two important enzymes regulating the formation and
      degradation of the active thyroid hormone, 3,5,3'-triiodothyronine (T3). Selenium
      is thus required for such complex processes as normal growth, brain development,
      and metamorphosis, all of which are thyroid hormone dependent. Structural and
      functional analyses of the type 1 deiodinase mRNA allowed identification of the
      selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the
      3' untranslated region of the mRNA. SECIS elements with conserved sequence and
      structural features are also present in the 3' untranslated regions of the mRNAs
      encoding selenoprotein P and the glutathione peroxidase family of selenoproteins.
      These elements are necessary and sufficient for directing selenocysteine
      incorporation into the deiodinases and the other mammalian selenoproteins.

PMID- 8527224
TI  - Regulation of tight-junction permeability during nutrient absorption across the
      intestinal epithelium.
AB  - Tight junctions are located at the luminal aspect of adjacent epithelial cells
      and form a barrier that limits the paracellular diffusion of hydrophilic solutes.
      In recent years, evidence has accumulated to indicate that tight-junction
      permeability is regulated by the absorption of various nutrients. In this review,
      we present the physiological basis and importance of tight-junction regulation in
      intestinal epithelium. The molecular structure of tight junctions and their
      interactions with the cell cytoskeleton as well as the physical and chemical
      forces that influence tight junction permeability are described. Much of this
      review addresses the controversial Pappenheimer hypothesis, which states that a
      major portion of intestinal glucose absorption occurs through tight junctions and
      not by saturable transcellular active transport. The absorption of a significant
      portion of glucose through tight junctions requires increased junctional
      permeability, a very high intralumenal glucose concentration, and a sufficient
      osmotic gradient to promote volume flow.

PMID- 8527225
TI  - Erythropoietin.
AB  - Erythropoietin (Epo), the first growth factor to be discovered, is an endocrine
      hormone produced by specialized renal cells. The rate of Epo production is
      determined primarily by the oxygen demands of these renal cells relative to their
      oxygen supply. However, Epo production is modulated by various hormones,
      nutritional factors, cytokines, and the integrity of the erythron. Epo interacts
      with specific receptors found almost exclusively on erythroid progenitors. This
      interaction results in an expansion of the number of the erythroid progenitor and
      triggers late committed progenitors to undergo terminal maturation when provided
      with essential nutrients. Recombinant human Epo (rHuEpo) is commercially
      available for human use. It is safe, easily administered, and almost universally
      effective in treating the anemia of patients with renal failure. It has also been
      successful in treating the anemia of some patients with neoplasms,
      myelodysplastic syndromes, HIV infection, rheumatoid arthritis, and aplastic
      anemia. Much remains to be learned about the regulation of Epo production, the
      physiologic actions of Epo, and how best to use this growth factor in the
      treatment of anemia.

PMID- 8527226
TI  - Dietary management of X-linked adrenoleukodystrophy.
AB  - Adrenoleukodystrophy (ALD) is an X-linked disorder that involves mainly the
      nervous system white matter and adrenal cortex. It is associated with the
      accumulation of saturated very-long-chain fatty acids (VLCFAs), such as
      hexacosanoic acid (C26:0), that occurs as a result of the impaired capacity to
      degrade these substances, a reaction that normally takes place in the peroxisome.
      The VLCFAs originate from the diet and are also synthesized endogenously.
      Interest in dietary therapy arose from the observation that the administration of
      oils containing erucic and oleic acid (Lorenzo's oil), when combined with
      restriction of dietary intake of VLCFAs, can normalize plasma VLCFA levels in ALD
      patients. Clinical results in patients who are already symptomatic have been
      disappointing. However, preliminary data, still in need of confirmation, suggest
      that dietary therapy begun in asymptomatic patients can reduce the frequency and
      severity of later neurological disability.

PMID- 8527227
TI  - The importance of menaquinones in human nutrition.
AB  - Bacterially produced menaquinones, 2-methyl-1,4-naphthoquinones with an
      unsaturated polyisoprenoid chain at the 3-position, are biologically active forms
      of vitamin K that are present in high concentrations in the human lower bowel.
      Menaquinones are found in human liver and circulate in human plasma at much
      higher concentrations than previously thought. Numerous case reports of
      antibiotic-induced, vitamin K-responsive hypothrombinemias have been taken as
      evidence that menaquinones contribute importantly to satisfying the human vitamin
      K requirement. However, more recent production of symptoms of vitamin K
      insufficiency in normal human subjects by dietary restriction of vitamin K argues
      against their nutritional significance. Current data support the view that
      menaquinones may partially satisfy the human requirement but that their
      contribution is much less than previously thought.

PMID- 8527228
TI  - The mechanism of action of vitamin K.
AB  - Vitamin K is the blood-clotting vitamin. The mechanism of action of vitamin K is
      discussed in terms of a new carbanion model that mimics the proton abstraction
      from the gamma position of protein-bound glutamate. This is the essential step
      leading to carboxylation and activation of the blood-clotting proteins. The model
      comprises an oxygenation that is coupled to carbon-carbon bond formation, as is
      the oxygenation of vitamin K hydroquinone to vitamin K oxide. The model
      hypothesis is also supported by the mechanism of inhibition of the carboxylase by
      HCN, which acts as an acid-base inhibitor rather than a metal-complexing
      inhibitor. The new model postulates a dioxetane intermediate that explains the
      presence of a second atom of 18O (from 18O2) incorporated into vitamin K oxide in
      the course of the enzymatic carboxylation. Finally, the chemistry developed here
      has been used to define the active site of vitamin K hydroquinone as the carbon
      carbon bond adjacent to the methyl group.

PMID- 8527229
TI  - Molecular actions of insulin on glucose transport.
AB  - Low basal glucose uptake by insulin-sensitive muscle and adipose cells reflects
      rapid endocytic retrieval of GLUT4 glucose transporters from the cell surface and
      their retention in intracellular membranes. Both GLUT4 endocytosis and its
      intracellular retention are governed by a dileucine motif in its COOH-terminal
      region. Acute stimulation of sugar uptake by insulin results from GLUT4
      redistribution to the plasma membrane and may reflect disruption of dileucine
      motif function as well as enhanced bulk membrane exocytosis. Candidate signaling
      elements for these postulated actions of insulin are PI 3-kinase and p21ras, both
      acutely activated by the hormone. Recent work in our laboratory and others
      demonstrates the localization of PI 3-kinase to intracellular membranes via its
      docking to the insulin receptor substrate-1 (IRS-1). An important hypothesis for
      future testing is that 3' phosphoinositides generated in the endosomal
      tubulovesicular system in response to insulin cause budding or movements of GLUT4
      containing membranes to the cell surface.

PMID- 8527230
TI  - Trans fatty acids and their effects on lipoproteins in humans.
AB  - Trans fatty acids raise plasma low-density lipoprotein (LDL) cholesterol levels
      in volunteers when exchanged for cis unsaturated fatty acids in the diet. In
      addition, trans fatty acids may lower high-density lipoprotein (HDL) cholesterol
      levels and raise triglyceride and lipoprotein(a) levels in plasma. Trans and cis
      unsaturated fatty acids are thus not equivalent, and diets aimed at reducing the
      risk of coronary heart disease should be low in both trans and saturated fatty
      acids.

PMID- 8527231
TI  - Apolipoprotein E and the apolipoprotein E-deficient mouse.
AB  - Apolipoprotein E (apoE) is one of several lipoprotein transfer genes. A primary
      function of this protein is the mediation of receptor-mediated lipoprotein
      removal from the blood. Several studies have demonstrated that genetic variation
      at the apoE locus is associated with an increased risk of developing
      atherosclerosis, and recent studies implicate this same genetic variation in
      determining susceptibility to Alzheimer's disease. An apoE-deficient mouse has
      been created to further understand the role of apoE in these areas. This review
      briefly discussed the biological and clinical importance of this protein and
      describes the early experiments performed in the apoE-deficient mouse.

PMID- 8527232
TI  - Whole-body protein turnover in humans--past, present, and future.
AB  - Protein turnover is a fundamental biological process in all living organisms. The
      study of protein turnover in human subjects, and in the body as a whole, is of
      relatively recent origin. In this review, I summarize briefly how this field of
      work has expanded over the past 25 years, with emphasis on conceptual problems
      and controversies, particularly those related to methods of measurement. We
      cannot be certain that our estimates are accurate because no method of
      verification exists, but progress will be made through successive approximations.
      Some of the applications are described in different physiological and
      pathological states such as growth and trauma, and possible directions for
      fruitful future research are indicated.

PMID- 8527233
TI  - Lactoferrin: molecular structure and biological function.
AB  - Lactoferrin is an 80-kDa, iron-binding glycoprotein present in milk and, to a
      lesser extent, in exocrine fluids such as bile and tears. It consists of a single
      chain polypeptide with two gobular lobes and is relatively resistant to
      proteolysis. The complete cDNAs for lactoferrin from human milk, neutrophils, and
      bovine milk have been reported, and recombinant proteins have been produced.
      Owing to its iron-binding properties, lactoferrin has been proposed to play a
      role in iron uptake by the intestinal mucosa and to act as a bacteriostatic agent
      by withholding iron from iron-requiring bacteria. Its presence in neutrophils and
      its release during inflammation suggest that lactoferrin is also involved in
      phagocytic killing and immune responses. Additionally, lactoferrin may function
      in ways not related to iron-binding, e.g. as a growth factor and as a
      bactericidal agent. This review attempts to evaluate these proposed functions and
      their biological significance in more detail.

PMID- 8527234
TI  - In vitro analysis of the centripetal migration mechanisms of developing LHRH
      neurons.
AB  - This study was designed to gain insight into the underlying mechanisms of the
      centripetal migration of developing LHRH neurons. The medial wall of the nasal
      pit (NAP) of 12.5-day-old rat embryos (E12.5) was cultured singly or together
      with the E12.5 medial-basal wall of the forebrain vesicles (mFV) or with the
      E14.5 median eminence-arcuate complex (ME-Arc). Further, the NAP was cultured
      with the mFV and ME-Arc or with the mFV and nasal mesenchyme (NM), which lay
      between the mFV and the NAP, of E12.5 embryos (triple culture). The NAP gave rise
      first to fibers labeled with anti-neural cell adhesion molecules (NCAM) and then
      to LHRH neurons. In co-cultures, NAP- and brain-derived NCAM fibers connected the
      NAP and brain cultures, and frequently linked with each other to form knots at
      the periphery. LHRH neurons migrating along the NAP-derived fibers directly or
      indirectly entered brain cultures. In the latter case, the cells strayed along
      the way from the NAP-derived fibers to the brain-derived fibers at the knots and
      migrated retrogradely along the latter fibers to enter into the brain tissues;
      this occurred most frequently into the E14.5 ME-Arc. In triple cultures, abundant
      NCAM fibers emerging from the NAP were only found when the NM lay between the NAP
      and mFV; the fibers converged further to the mFV. These findings help elucidate
      the mechanisms underlying the centripetal LHRH cell migration from the NAP to the
      hypothalamus.

PMID- 8527235
TI  - Junctions between early developing osteoblasts of rat calvaria as revealed by
      freeze-fracture and ultrathin section electron microscopy.
AB  - Although intercellular junctions have been described between mature lamellar bone
      cells, little has been known about junctions between osteoblasts in early
      developing bone. We therefore conducted a freeze-fracture and ultrathin section
      study on developing calvaria of rat embryos aged 17-19 days to determine what
      types of intercellular junctions appear between osteoblasts in early
      osteogenesis. We observed that three main types of junctional structures, i.e.,
      adherens of the macular type, gap, and focal tight junctions, coexist between
      osteoblasts in early developing bone. Their possible involvement in early
      morphogenetic events is discussed. Tight junctions are considered to be involved
      in compartmentalization of the early matrix and final polarization of
      osteoblasts.

PMID- 8527236
TI  - Morphological changes in the smooth muscle cells of the mouse lower oviduct
      during pregnancy and post-partum.
AB  - The muscle coat of the lower region of the mouse oviduct undergoes morphological
      changes during pregnancy and post-partum. Ultrastructural examination and
      morphometrical findings show that, during pregnancy, the smooth muscle cells
      undergo a significant increase in both the number of mitochondria and caveolae
      and in the extension of the rough endoplasmic reticulum and Golgi apparatus,
      suggesting an enhancement of metabolic activities, especially protein synthesis.
      Within two days after delivery, the number of mitochondria and caveolae is
      similar to that of non-pregnant mice, whereas the extension of the rough
      endoplasmic reticulum and Golgi apparatus further increases significantly. The
      cytological signs of enhanced protein synthesis in the smooth muscle cells of the
      lower oviduct during pregnancy and, especially, in the post-partum period are
      probably related to a remodelling of the intercellular connective tissue matrix.

PMID- 8527237
TI  - Immunohistochemical distribution of intestinal 15 kDa protein in human tissues.
AB  - The distribution of human intestinal 15 kDa protein (I-15P), a new fatty acid
      binding protein (FABP), was observed in normal tissues using immunohistochemical
      techniques. The antiserum against human I-15P intensely reacted with the villous
      epithelium of the terminal ileum but not with the enterocytes of the crypts.
      Although the surface epithelium of the stomach and villous epithelium of the
      duodenum showed weak reactivities, the epithelial cells of the jejunum, proximal
      ileum, colon and rectum, and also glandular epithelia with intestinal metaplasia
      of the stomach were not immunostained. The other human tissues examined were
      negative for anti-human I-15P antibody. Human I-15P thus represents a
      distinctive, confined tissue distribution different from the other FABPs and is
      expected to serve as a useful cellular marker of terminal ileal enterocytes.

PMID- 8527238
TI  - Ultrastructural recognition of cells with dendritic cell morphology in human
      aortic intima. Contacting interactions of Vascular Dendritic Cells in athero
      resistant and athero-prone areas of the normal aorta.
AB  - Analysis of serial ultrathin sections of the human aortic intima detected a new
      cell yet to be described in the literature. These cells, which we have designated
      Vascular Dendritic Cells, appeared in contact with each other and with other
      intimal cells. Vascular dendiritic cells are characterised by ultrastructural
      features similar to those of dendritic cells, including a well developed smooth
      endoplasmic reticulum and the presence of several processes which were 3-5 or
      more times in excess of the size of the cell body. In areas of the normal aorta
      resistant to atherosclerosis, vascular dendritic cells were mainly localised in
      the subendothelial layer where they contacted both endothelial cells and smooth
      muscle cells. In areas of the normal aorta predisposed to atherosclerosis,
      vascular dendritic cells were distributed throughout the intima and the cellular
      interactions were altered with the vascular dendritic cells, developing multiple
      contacts with monocyte/macrophages and lymphocyte-like cells. Aortic areas
      predisposed to atherosclerosis showed the destruction of some vascular dendritic
      cell processes where they apposed endothelial cells. We speculate that vascular
      dendritic cells (VDCs) are a variety of dendritic cell and are involved in the
      maintenance of homeostasis in normal arterial intima. Vascular dendritic cells
      may be important in the development of atherosclerotic lesions, possibly through
      an immune mechanism.

PMID- 8527239
TI  - Immunolocalization of CD44 and heparan sulfate chains on the stratum intermedium
      and papillary layer in the rat enamel organ.
AB  - We studied the immunohistochemical localization of CD44 and heparan sulfate (HS)
      chains in rat enamel organ by confocal laser scanning microscopy and transmission
      electron microscopy. We also investigated the binding sites of basic fibroblast
      growth factor (bFGF), one of the heparin-binding growth factors (HBGF), on
      Microslicer-sections to clarify its role in the cell-cell interaction of HS. At
      the differentiation stage of ameloblast, weak immunoreactivity for CD44 was
      detected on the plasma membrane of the inner enamel epithelium, external enamel
      epithelium and the cells adjacent to the inner enamel epithelium. In accordance
      with the differentiation of preameloblasts into secretory ameloblasts, this
      immunoreactivity increased in stratum intermedium cells. At the secretory stage,
      stratum intermedium cells showed the most intense immunoreactivity in the enamel
      organ. At the maturation stage, strong immunoreactivity was seen on papillary
      layer cells. On the other hand, the lateral plasma membrane of ruffle-ended (RA)
      and smooth-ended ameloblast (SA) showed weak reactivity. No immunoreactivity was
      detected on the ruffled border of RA and the distal plasma membrane of SA.
      Immunolocalization of HS chains was similar to that of CD44. The binding activity
      of bFGF was also intense on stratum intermedium cells and papillary layer cells.
      These findings suggest that: 1) stratum intermedium cells and papillary layer
      cells express CD44 and HS chains in accordance with their differentiation; 2) HS
      chains on the plasma membrane of these cells may regulate calcium transport by
      their negative charge; and 3) HS chains on the stratum intermedium and papillary
      layer may play an important role in the differentiation and activity of
      ameloblasts by preserving HBGF.

PMID- 8527240
TI  - Postnatal development of lymphoid follicles in rat Peyer's patches, with special
      reference to increased follicle number.
AB  - The postnatal development of Peyer's patches was investigated using routine
      histological and immunohistochemical techniques, focusing especially on the
      formation and increase in number of lymphoid follicles. In addition, we studied
      the influence on the development of lymphoid follicles in Peyer's patches of a
      sublethal dose of whole-body X-irradiation at an earlier postnatal age. At 1 day
      after birth, surface-IgM (sIgM)-bearing cells (B lymphocytes) were scattered
      throughout the Peyer's patch. At Day 3, sIgM-bearing cells had accumulated to
      form primary follicles in association with domed elevations. OX2-positive
      reticular cells (FDC) were detected in the centers of primary follicles at Day 5.
      The first appearance of germinal centers within lymphoid follicles was noted at
      18 days, and at 21 days almost every follicle contained a germinal center. At Day
      5, each Peyer's patch contained 6-8 lymphoid follicles, with the lymphoid
      follicles subsequently increasing in size and number. The mean number of
      follicles per Peyer's patch became 11.1, the adult level, at 21 days, and
      remained at this level for the next 15 weeks, even though respective follicles
      continued to enlarge during the observation period. Three-week-old rats received
      400 rad whole-body X-irradiation. At 3 and 7 days after treatment, lymphocytes
      were largely depleted from Peyer's patches, leaving behind the structural
      framework of the lymphoid follicles, interfollicular zones and domes. Stromal
      cells in the follicle remnants retained a positive reaction to OX2.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8527241
TI  - Segregated localization of immunocompetent cells and osteoclasts in the
      periodontal ligament of the rat molar.
AB  - The spatial distribution of dendritic cells, macrophages, and their respective
      precursor cells in the periodontal ligament of rat molars was examined by means
      of ACPase enzyme histochemistry and immunohistochemistry. Intense reactions for
      ACPase were localized in both the multinucleated-and mononucleated cells of the
      periodontal ligament located exclusively in the portions of physiological bone
      resorption due to the physiological migration of the molar teeth.
      Immunohistochemical staining with OX6-monoclonal antibody that recognizes antigen
      presenting cells such as dendritic cells and macrophages revealed the
      localization of immunopositive cells predominantly in the portions of the
      periodontal ligament that showed only trace reactions for ACPase. On the other
      hand, a large number of ED1-immunopositive cells, comprising a broad spectrum of
      cells of monocyte origin including dendritic cells and osteoclasts, displayed an
      almost even distribution throughout the periodontal ligament. Our current study
      is the first to show clear-cut in vivo morphological evidence that the cells of
      the bone-resorbing, osteoclastic cell lineage and those of the non-bone
      resorbing, macrophagic and/or dendritic cell lineages are exclusively localized
      in roughly the distal and proximal regions of the periodontal ligament of rat
      molars, respectively. An advantage is proposed for the use of the rat molar
      periodontal ligament as an in vivo model system for pursuing differentiation
      pathways of cells of the monocyte lineage, particularly of the osteoclastic
      cells.

PMID- 8527242
TI  - Neurons with perineuronal sulfated proteoglycans in the human visual cortex, with
      special reference to their reactions to lectins.
AB  - The human visual cortex, especially its ganglionic lamina, was found to contain
      many neurons with perineuronal sulfated proteoglycans which were stained with
      cationic iron colloid and aldehyde fuchsin. It also contained many neurons with
      surface glycoproteins labeled with lectin Vicia villosa agglutinin (VVA) or
      Glycine max agglutinin (SBA). Double staining frequently showed that the neurons
      stained with cationic iron colloid were not labeled with lectin VVA or SBA.
      Hyaluronidase and chondroitinase ABC/heparitinase/keratanase digestions
      eliminated the perineuronal cationic iron colloid reaction, but never interfered
      with the cell surface lectin labeling. These findings indicate that the cell
      surface glycoproteins reactive to lectin VVA or SBA are neither structural
      elements nor adhesive molecules of the proteoglycans. Double staining further
      demonstrated that in some neurons with perineuronal sulfated proteoglycans, the
      cytoplasm was labeled with lectin Arachis hypogaea agglutinin (PNA). It was
      further noticed that the lectin VVA-labeled neurons were not always identical
      with the neurons labeled with lectin SBA or with lectin PNA.

PMID- 8527243
TI  - Changes in the mouse exocrine pancreas after pancreatic duct ligation: a
      qualitative and quantitative histological study.
AB  - The pancreatic duct from the splenic lobe, the largest lobe of the pancreas in
      the mouse, was ligated at 6 weeks of age, with histological and cytological
      changes in the organ examined 1 day to 16 weeks after the ligation. Changes in
      the volumes of the pancreatic lobe, exocrine tissue, and interstitial tissue as
      well as relative total numbers of each cellular element in the organ after duct
      ligation were stereologically obtained using serial sections of the whole
      pancreas. Cell sizes, degenerated cell and mitotic cell indices, and nuclear
      densities of the acinar and ductal cells were also obtained. After duct ligation,
      the volume of the pancreas increased by interstitial edema in the first 2 days
      but rapidly decreased thereafter due to atrophy of the exocrine tissue, amounting
      to 10% or less of normal volume by 7 days. The acinar cells showed an
      accumulation of the zymogen granules, cytoplasmic condensation and a pyknotic
      figure of the nucleus; they then were thoroughly deleted with appearance of
      numerous macrophages. This cell death was suggested to be due to apoptosis. On
      the other hand, the ductal cells remained in the atrophic pancreas and
      proliferated with mitotic figures to two times the normal frequency at 3 days,
      and then formed duct-like structures lacking in the acinar cells. After 2 week,
      the ductal cells slowly decreased in number also due to cell death, but the
      pancreas became gradually enlarged by intralobular fatty replacement, to reach a
      volume approximating that of normal 8 weeks after duct ligation. The
      stereological method serves for the correct evaluation of cell dynamics including
      the deletion and proliferation of the cells in the whole organ.

PMID- 8527244
TI  - A differential staining method for adenohypophyseal cells.
AB  - A modification of azan staining (Heidenhain, 1915) for a better differential
      demonstration than previously of adenohypophyseal cells is reported. Human
      hypophyses were fixed in Bouin's solution, washed in 70% alcohol, dehydrated and
      then embedded in paraffin. Sections of about 5 microns thickness were cut and
      mounted on albumin-coated glass slides. These sections were gently oxidized with
      a mixture of potassium permanganate and sulphuric acid, and then stained
      according to the original azan technique; thereafter a procedure of staining with
      aniline blue was added. With this improvement, human adenohypophyseal cells were
      clearly classified into six groups on the basis of the color and intensity of
      staining of the cytoplasm. The alpha-acidophilic cells were stained clear red
      with azocarmine and the epsilon-acidophilic cells, orange-red with orange G,
      respectively. With aniline blue, beta-basophilic cells stained a deep blue, while
      delta-basophilic cells were more weakly stained. The gamma-chromophobic cells
      were faintly stained red, and the ACTH-cells very faintly blue. Collagenous
      fibers developed a blue color, while erythrocytes were orange-red to red. This
      modified method produces much better results in differential staining of the
      adenohypophyseal cells than either the original azan or Masson-Goldner staining
      methods.

PMID- 8527245
TI  - Case management.

PMID- 8527246
TI  - Technology and home care.

PMID- 8527247
TI  - Nursing minimum data set.

PMID- 8527248
TI  - Pediatric hospice nursing.

PMID- 8527249
TI  - Faculty practice: interest, issues, and impact.

PMID- 8527250
TI  - Professionalization of nurse practitioners.

PMID- 8527251
TI  - Feminism and nursing.

PMID- 8527252
TI  - Health risk behaviors for Hispanic women.

PMID- 8527253
TI  - Quality of life and the spectrum of HIV infection.

PMID- 8527254
TI  - Physical health of homeless adults.

PMID- 8527255
TI  - Child sexual abuse: initial effects.

PMID- 8527256
TI  - Neuro-behavioral effects of childhood lead exposure.

PMID- 8527257
TI  - Science, medicine and clinical pharmacology. The Lilly Lecture 1994.

PMID- 8527258
TI  - Systemic effects of S-nitroso-glutathione in the human following intravenous
      infusion.
AB  - Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet aggregation.
      At present the clinical use of NO donors as inhibitors of platelet activation is
      limited by their concomitant hypotensive effect. The new NO donor S-nitroso
      glutathione (GSNO) has a significant antiplatelet effect at doses that cause only
      a small decrease in blood pressure in rats. We have examined the antiplatelet and
      vasodilator properties of this nitrosothiol following systemic intravenous
      infusion in the human. GSNO was administered intravenously to 10 normal females
      of reproductive age noting changes in blood pressure, pulse and reported side
      effects. Ex vivo platelet aggregation to ADP was then performed in a platelet
      ionized calcium lumiaggregometer on blood samples taken both before and after the
      infusions. Side effects such as headache or palpitations occurred only in two
      subjects at the highest infusion rate of 250 micrograms min-1. Blood pressure and
      pulse did not vary significantly during the study. Ex vivo platelet aggregation
      in response to ADP was significantly reduced by the infusion. These results
      suggest that GSNO is a more potent inhibitor of platelet activation than it is a
      vasodilator and therefore potentially represents a more clinically useful NO
      donor than has so far been available where an anti-thrombotic effect is required.

PMID- 8527259
TI  - Enalapril overdose and the corrective effect of intravenous angiotensin II.

PMID- 8527260
TI  - Acute liver injury and droxicam use in the region of Friuli-Venezia Giulia.

PMID- 8527261
TI  - Treatment of Parkinson's disease in a patient with acute intermittent porphyria.

PMID- 8527262
TI  - The role of the renin-angiotensin and natriuretic peptide systems in the
      pulmonary vasculature.
AB  - 1. The role of vasoactive peptide systems in the pulmonary vasculature has been
      studied much less extensively than systemic vascular and endocrine effects. The
      current understanding of the role of the renin-angiotensin (RAS) and natriuretic
      peptide systems (NPS) in the pulmonary circulation is therefore reviewed. 2.
      Plasma concentrations of angiotensin II, the main vasoactive component of the
      RAS, are elevated in pulmonary hypertension and may interact with hypoxaemia to
      cause further pulmonary vasoconstriction. Pharmacological manipulation of
      angiotensin II can attenuate hypoxic pulmonary vasoconstriction but larger
      studies are needed to establish the efficacy of this therapeutic strategy in
      established pulmonary hypertension. 3. Although all the known natriuretic
      peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear
      to have pulmonary vasorelaxant activity in humans. ANP and BNP can also attenuate
      hypoxic pulmonary vasoconstriction, suggesting a possible counter-regulatory role
      for these peptides. Inhibition of ANP/BNP metabolism by neutral endopeptidase has
      been shown to attenuate development of hypoxic pulmonary hypertension but this
      property has not been tested in humans. 4. It is also well established that there
      are potentially important endocrine and systemic circulatory interactions between
      the RAS and NPS. This also occurs in the pulmonary circulation and in humans,
      where at least BNP acts to attenuate angiotensin II induced pulmonary
      vasoconstriction. This interaction may be particularly relevant as a mechanism to
      counter-regulate overactivity of the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527263
TI  - The dose dependency of the alpha- and beta-adrenoceptor antagonist activity of
      carvedilol in man.
AB  - 1. The alpha- and beta-adrenoceptor antagonist activity of carvedilol, a beta
      adrenoceptor antagonist with vasodilating properties, and labetalol were
      investigated in 10 healthy male subjects. They received infusions with serially
      increasing concentrations of isoprenaline and phenylephrine before and after
      single oral doses of carvedilol 6.25, 12.5 and 25 mg, labetalol 400 mg and
      placebo at weekly intervals in a double-blind randomised manner. An exercise step
      test was performed at the end of the infusions. 2. The dose of isoprenaline
      required to increase heart rate by 25 beats min-1 (I25) and the dose of
      phenylephrine required to increase systolic and diastolic blood pressure by 20 mm
      Hg (PS20 and PD20) were calculated using a quadratic fit to individual dose
      response curves. Comparisons were made with placebo and P < 0.05 was considered
      significant. 3. The I25 was increased by carvedilol 25 mg and labetalol 400 mg (P
      < 0.05). The dose ratios at I25 were: carvedilol 6.25 mg 2.1 +/- 1.6, carvedilol
      12.5 mg 3.1 +/- 1.9, carvedilol 25 mg 6.4 +/- 4.9 and labetalol 400 mg 8.8 +/-
      4.4. 4. The PS20 was increased by labetalol 400 mg (P < 0.05). The dose ratios at
      PS20 were: carvedilol 6.25 mg 1.0 +/- 0.2; 12.5 mg, 1.2 +/- 0.2; 25 mg, 1.3 +/-
      0.4 and labetalol 400 mg 2.2 +/- 0.8. 5. The PD20 was increased by labetalol 400
      mg (P < 0.05). The dose ratios at PD20 were: carvedilol 6.25 mg 1.1 +/- 0.3; 12.5
      mg, 1.3 +/- 0.3; carvedilol 25 mg 1.3 +/- 0.4 and labetalol 400 mg 2.1 +/-
      0.8.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527264
TI  - Postextrasystolic potentiation in patients with ischaemic heart disease:
      influence of inotropic agents.
AB  - 1. The extent of postextrasystolic potentiation (PESP) has been considered a
      useful parameter for evaluating myocardial contractile reserve in the presence of
      myocardial stunning or hibernation. Extent of PESP appears to reflect an
      interaction between myofibrillar calcium concentration and function of the
      contractile apparatus. However, potential for cardiovascular drugs including
      agents modifying adenosine 3' 5'-cyclic monophosphate concentration to influence
      the extent of PESP in man has not been extensively studied. 2. In 35 patients
      undergoing diagnostic coronary angiography, we investigated the relationship
      between the extrasystolic test pulse interval (ETPI) and left ventricular (LV)
      +dP/dtmax of a postextrasystolic contraction. The influence of three
      inotropically active agents on this relationship was examined following
      intravenous bolus injection (metoprolol, 4 mg; sotalol, 20 mg; and milrinone, 1
      mg). 3. The patient group examined had predominantly preserved LV function (LVEF
      67% with 95% confidence intervals 63%, 71%). In the doses utilized, all agents
      exerted significant effects on LV+dP/dtmax during atrial pacing: reduction of
      12.3% (6.4, 18.2) for metoprolol (P < 0.0005), and 10.9% (4.2, 17.6) for sotalol
      (P < 0.005); and increase of 11.8% (1.3, 22.3) for milrinone (P < 0.05). 4. With
      the postextrasystolic interval identical to baseline pacing cycle length,
      postextrasystolic potentiation of LV+dP/dtmax varied inversely with ETPI. None of
      the three agents investigated significantly affected this relationship. 5. These
      results demonstrate that the extent of PESP is unaffected by 'pure' beta
      adrenoceptor antagonism, (+/-)-sotalol or phosphodiesterase inhibition in man.
      Hence pharmacotherapy with these agents is unlikely to affect assessment of
      extent of PESP.

PMID- 8527265
TI  - Effect of captopril, enalaprilat and mercaptopropionyl glycine (MPG) on the
      oxidative activity of human isolated neutrophils.
AB  - 1. Neutrophil NADPH oxidase produces the superoxide anion (O2-) anion radical
      from oxygen. The thiol containing ACE inhibitor, captopril has been reported to
      inhibit isolated NADPH oxidase. The above effect of captopril, if present in
      intact cells, could contribute to the ability of this drug to alleviate
      neutrophil-mediated tissue damage. We have, therefore, investigated the effect of
      captopril on the oxidative activity of intact human isolated neutrophils. 2. The
      effects of captopril on neutrophil oxidative activity were compared with those of
      enalaprilat (a non-thiol ACE inhibitor) and N-mercaptopropionyl glycine (MPG) (a
      simple thiol). 3. The oxidative response of PMA-stimulated neutrophils measured
      by lucigenin chemiluminescence was not affected by any of these test agents. The
      thiol captopril and MPG (but not enalaprilat) caused an initial delay in luminol
      chemiluminescence production by PMA-stimulated neutrophils. 4. Captopril and MPG
      (but not enalaprilat) increased, rather than decreased oxygen uptake, when added
      to PMA-stimulated neutrophils. Thiol oxidation was determined to be, at least
      partly, responsible for the excess oxygen uptake observed. 5. NADPH oxidase
      activity in intact neutrophils was not affected by captopril, MPG or enalaprilat.
      The inhibition of NADPH oxidase activity is unlikely to contribute to the
      therapeutic effects of captopril and other thiols.

PMID- 8527266
TI  - A placebo controlled comparison of the effects of metoprolol and celiprolol on
      echo-Doppler measurements of cardiovascular function in normal volunteers.
AB  - 1. This study used a continuous-wave echo-Doppler method (Exerdrop) to
      investigate the effects of beta-adrenoceptor antagonism and partial agonism on
      cardiovascular responses at rest and during dynamic exercise. 2. A double-blind,
      randomised, placebo controlled comparison of metoprolol (50 mg) and celiprolol
      (200 mg) was undertaken in nine normal volunteers; single oral doses of
      medication were administered at weekly intervals. Rest and exercise (supine
      bicycle) haemodynamics were assessed at 0, 2, 4, 6 and 8 h following dosing. 3.
      Before dosing and after placebo, the aortic flow velocity, acceleration and
      velocity integral increased progressively during exercise, as did heart rate,
      blood pressure and cardiac output. 4. Following metoprolol 50 mg, heart rate was
      significantly reduced without change in systolic or diastolic blood pressure.
      Echo-Doppler peak acceleration and velocity decreased at rest. On exercise, heart
      rate and systolic blood pressure fell significantly; the increase in acceleration
      was significantly blunted compared with placebo (a decrease of 15.2% at rest and
      22.9% at 75 watts; P < 0.01 vs placebo). Peak velocity fell significantly by 75
      watts exercise. 5. Celiprolol 200 mg at rest significantly increased systolic
      blood pressure, peak acceleration and velocity. On exercise celiprolol, in
      contrast to metoprolol, did not reduce peak acceleration or peak velocity;
      however exercise heart rate and systolic blood pressure were significantly
      reduced. The difference between celiprolol and metoprolol in respect of peak
      acceleration persisted over the 8 h of the study. 6. These differences between
      metoprolol and celiprolol are compatible with the partial agonism of
      celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527267
TI  - Adenosine receptor-induced cyclic AMP generation and inhibition of 5
      hydroxytryptamine release in human platelets.
AB  - 1. We have assessed the effects of adenosine receptor agonists and antagonists on
      collagen-induced 5-hydroxytryptamine (5-HT) release and cyclic AMP generation in
      human platelets. 2. 5'-N-ethylcarboxamidoadenosine (NECA) and CGS 21680 elicited
      accumulations of cyclic AMP with mean EC50 values of 2678 and 980 nM,
      respectively. The maximal response to CGS 21680 was approximately half that of
      the response to 10 microM NECA. 3. NECA and CGS 21680 inhibited collagen-induced
      5-hydroxytryptamine release with mean EC50 values of 960 and 210 nM,
      respectively. The maximal response to CGS 21680 was approximately 25% of the
      response to 10 microM NECA. 4. The A1/A2a-selective adenosine receptor antagonist
      PD 115,199 was more potent as an inhibitor of NECA-elicited responses than the A1
      selective antagonist DPCPX with calculated Ki values of 22-32 nM and > 10 microM,
      respectively. 5. In the presence of a cyclic AMP phosphodiesterase inhibitor, the
      effects of CGS 21680 on cyclic AMP accumulation and 5-HT release were enhanced to
      levels similar to those elicited by 10 microM NECA. In the absence of
      phosphodiesterase inhibition, CGS 21680 did not antagonise the effects of NECA.
      Furthermore, endogenous adenosine did not contribute to the effects of CGS 21680
      when phosphodiesterase was inhibited. 6. We conclude that an A2a adenosine
      receptor appears to be involved in the NECA-elicited increases in cyclic AMP
      levels and inhibition of 5-HT release in human platelets.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8527268
TI  - Factors affecting the absolute bioavailability of nifedipine.
AB  - 1. Nifedipine was administered to eight volunteers (seven Caucasian, one East
      Asian of Chinese origin) as a single 10 mg capsule orally and as 2.5 mg
      intravenously. The pharmacokinetics were determined under fasting conditions and
      following 200 ml double strength grapefruit juice taken orally both 2 h before
      and at the time of dosing. 2. In a separate study, the pharmacokinetics of
      nifedipine were defined in eight South Asian volunteers (with both parents
      originating from the Indian subcontinent) following 10 mg nifedipine orally and
      2.5 mg intravenously. 3. The administration of grapefruit juice did not alter the
      pharmacokinetics of intravenous nifedipine, but resulted in a significantly
      increased area under the plasma concentration-time curve (AUC) (191 +/- 59 c.f.
      301 +/- 95 ng ml-1 h, P < 0.05) and bioavailability (0.63 +/- 0.18 c.f. 0.86 +/-
      0.15, P < 0.05) following oral nifedipine. The elimination half-life was
      unchanged by administration of grapefruit juice and there was no evidence of
      decreased formation of the nitropyridine first-pass metabolite. 4. The AUC of
      nifedipine after intravenous administration was significantly higher in South
      Asian subjects than in Caucasians (146 +/- 39 c.f. 74 +/- 18 ng ml-1 h, P <
      0.002). This was due to a lower systemic clearance in the South Asians which was
      50% of that in the Caucasians. The half-life was markedly prolonged in South
      Asians (4.1 +/- 1.9 c.f. 1.7 +/- 0.5 h, P < 0.002).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8527269
TI  - Pharmacokinetic and pharmacodynamic analysis of a novel leukotriene biosynthesis
      inhibitor, MK-0591, in healthy volunteers.
AB  - 1. The pharmacokinetic and pharmacodynamic properties of a novel 2-indolealkanoic
      acid derivative (MK-0591), a potent inhibitor of leukotriene biosynthesis, were
      investigated in healthy male Japanese volunteers. Single oral doses of 50, 125,
      250 and 500 mg and multiple oral doses of 125 mg twice daily for 9.5 days and 250
      mg once daily for 10 days were administered. 2. After the single-dose
      administration following overnight fasting, Cmax and AUC of MK-0591 in plasma
      increased in a dose-dependent manner, while elimination half-life remained
      constant (11.2-13.2 h) irrespective of dose. Food intake decreased Cmax and AUC
      by 71% and 68%, respectively, at a dose of 250 mg. With respect to multiple-dose
      administration before meals, there were no significant differences in the
      pharmacokinetic parameters between the first and last days, indicating a lack of
      significant accumulation of MK-0591 in plasma. Urinary recovery as the unchanged
      form was negligible throughout the study. 3. Ionophore-stimulated production of
      leukotriene B4 (LTB4) in blood ex vivo was inhibited significantly from 1 h until
      12 to 48 h after single-dose administration as compared with predose value. In
      parallel, the urinary excretion of endogenous leukotriene E4 (LTE4) was
      significantly decreased from 4 to 8 h until 48 to 72 h after drug administration.
      Reduction of ionophore-stimulated LTB4 biosynthesis and urinary excretion of LTE4
      following single administration of MK-0591 was statistically significant as
      compared with placebo group, and the duration of inhibition of LTB4 biosynthesis
      was dose-related.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527270
TI  - Stereoselective disposition of ibuprofen in patients with compromised renal
      haemodynamics.
AB  - 1. The primary aim of this study was to assess the impact of renal haemodynamics
      on the pharmacokinetic behaviour of ibuprofen enantiomers. Thirty-two patients
      and ten age-matched healthy volunteers participated in this study. These patients
      had at least one of the following risk factors for cardiovascular disorders:
      hypertension, diabetes mellitus, hyperlipidaemia and hyperuricaemia with or
      without consequent complications such as coronary artery disease, congestive
      heart failure, cerebral vascular disease, and chronic renal failure. Renal
      function in these patients was thus characterized by unstable renal haemodynamics
      that might render them susceptible to ibuprofen-incurred renal damage. 2. Each
      subject received a single oral dose of 800 mg of racemic ibuprofen. The
      pharmacokinetic parameters of (S)- and (R)-ibuprofen, t 1/2(S), t 1/2(R), AUC(S),
      AUC(R), V/F(R), and CL/F(R), for each individual were determined from respective
      plasma concentration-time curves. To assess the effect of individual clinical
      conditions on the disposition of ibuprofen enantiomers, the arithmetic means of
      these pharmacokinetic parameters for each disease group were compared with those
      of the healthy volunteers by a t-test. 3. All of these disease groups showed
      elevated AUC(S) and higher (S)/(R) AUC ratios. These disease states along with
      gender and age were analyzed by multiple linear regression to discern significant
      factors for elevating AUC(S). Of these, advanced age (P = 0.02) and hypertension
      (P = 0.03) were identified as independent factors contributing to AUC(S) increase
      in this population. Thus, patients with these two clinical conditions are at
      particular risk from the adverse renal effect of ibuprofen.

PMID- 8527271
TI  - Pharmacokinetics of ketoprofen enantiomers after different doses of the racemate.
AB  - The pharmacokinetics of the enantiomers of ketoprofen after oral administration
      of 12.5 mg, 25 mg and 50 mg and i.v. administration of 50 mg racemic ketoprofen
      to 24 healthy subjects were investigated. The AUC values of R- (r2 = 0.929) and S
      ketoprofen (r2 = 0.930) were proportional to dose. The absolute bioavailability
      of the 50 mg oral dose was 84.5 (s.d. 20.6) % and 81.4 (18.0) % for R-ketoprofen
      and S-ketoprofen, respectively. With the exception of AUC values no dose
      dependent differences in pharmacokinetic parameters were observed. However, the R
      enantiomer had higher AUC, lower clearance data and higher Cmax values than the S
      form after oral administration. The results suggest that stereochemical and
      pharmacokinetic considerations cannot explain the lack of dose response observed
      with ketoprofen doses below 50 mg.

PMID- 8527272
TI  - The effect of delay, multiple actuations and spacer static charge on the in vitro
      delivery of budesonide from the Nebuhaler.
AB  - A multistage liquid impinger was used to determine the amount of budesonide
      available from the Nebuhaler spacer device following alteration of spacer static
      charge, delay in sampling from the spacer, and multiple actuations of the metered
      dose inhaler into the spacer prior to sampling. The mean amount of budesonide
      (s.d.) recovered per 200 micrograms actuation in particles smaller than 5 microns
      increased from 30.5 micrograms (8.8) to 69.3 micrograms (17.9) with a low static
      spacer. A 20 s delay between actuation and inhalation reduced the amount
      recovered to 10.9 micrograms (3.2), but no reduction was seen when using a low
      static spacer after the same delay. Multiple actuations into the spacer before
      sampling also reduced the recovery to 24.8 micrograms (3.4) after two actuations,
      and 13.5 micrograms (7.6) after five actuations. When using a Nebuhaler with
      budesonide metered dose inhalers, more respirable drug will be obtained if the
      aerosol is inhaled immediately after actuation, and multiple actuations into the
      spacer device are avoided. Low static spacers may also improve drug delivery.
      Attention to the details of spacer use may reduce the incidence of therapeutic
      failure and the cost of inhaled medications.

PMID- 8527273
TI  - A survey of the administration of drugs to young infants. The Alspac Survey Team.
      Avon Longitudinal Study of Pregnancy and Childhood.
AB  - Medication which is given to young infants during the first months of life, an
      important period of development, may have effects on development which would not
      be observed in adults receiving the same drugs. The aim of this study was to
      estimate the numbers of children receiving various types of medication, including
      both prescription and non-prescription drugs, during the first 6 months of life.
      Self-completion questionnaires were posted to mothers participating in the Avon
      Longitudinal Study of Pregnancy & Childhood (ALSPAC) when their children were 6
      months of age. These questionnaires included enquiries about the administration
      of drugs to the study children. The study was based in the three Bristol-based
      health districts of Avon in the United Kingdom. The study population comprised of
      6973 children born in the 12 month period between the 1st July 1991 and the 30th
      June 1992. The majority of mothers, 96%, reported that their children had
      received medication, excluding vaccines, during the first 6 months of life. 35%
      had been given drugs from four or more different classes. Paracetamol had been
      given to 84% of the children, antibiotics to 30%. In view of potential effects of
      drug exposure on long term development, it is important that drugs which are
      administered to children are carefully assessed to ensure that they are not
      harmful.

PMID- 8527274
TI  - Comparative effects of antifungal agents on zidovudine glucuronidation by human
      liver microsomes.
AB  - Zidovudine (ZDV) is extensively metabolised by the liver to an inactive
      glucuronide (GZDV). Since ZDV is often administered with antimycotic drugs, we
      studied the effect of six systemic antifungal agents on the in vitro
      glucuronidation of ZDV by human liver microsomes. 5-fluorocytosine and
      itraconazole had no inhibitory effect whereas amphotericine B, ketoconazole,
      miconazole and fluconazole inhibited in vitro GZDV formation (Ki values were
      0.13, 0.08, 0.18 and 1.4 mM respectively).

PMID- 8527275
TI  - Marked enhancement by rifampicin and lack of effect of isoniazid on the
      elimination of quinine in man.
AB  - The effect of rifampicin and isoniazid pretreatment on the pharmacokinetics of
      quinine after a single oral dose (600 mg quinine sulphate) was studied in nine
      healthy young Thai male volunteers using a three-way randomized crossover design.
      Subjects were studied over three 2 day periods, during which they received no
      pretreatment, or pretreatment with daily 600 mg p.o. rifampicin for 2 weeks, or
      isoniazid 300 mg p.o. daily for 1 week, prior to quinine administration. The mean
      (+/- s.d.) clearance (CL/F) of quinine coadministered with rifampicin (0.87 +/-
      0.35 1 h-1 kg-1) was significantly greater than that of quinine alone (0.14 +/-
      0.05 1 h-1 kg-1). The mean difference in clearance from the control treatment was
      0.73 1 h-1 kg-1, with 95% confidence interval (C.I.) of 0.48 to 0.98. The unbound
      clearance (CLu/F) of quinine, which reflects the activity of the drug
      metabolizing enzymes, was considerably greater (6.9-fold) in subjects when
      rifampicin was coadministered with quinine than that of quinine alone (6.9 +/-
      3.6 vs 1.0 +/- 0.5 1 h-1 kg-1; the 95% C.I. for the mean difference was 3.3 to
      8.5). The mean elimination half-life of quinine when coadministered with
      rifampicin (5.5 +/- 3.0 h) was significantly shorter than when quinine was given
      alone (11.1 +/- 3.0 h; the 95% C.I. for the mean difference was -8.6 to -2.6). In
      contrast to rifampicin, pretreatment for 1 week with 300 mg oral isoniazid had no
      significant effects on the pharmacokinetics of quinine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8527276
TI  - The acceptability of resin therapy to patients attending a hospital lipid clinic.
AB  - Low dose cholestyramine ('Questran A') and colestipol ('Colestid Orange') were
      compared in a blinded two period crossover study of 55 patients attending a
      hospital lipid clinic. Colestipol was rated higher on a combined
      acceptability/palatability score. Both treatments reduced low density lipoprotein
      (LDL) cholesterol to a similar extent.

PMID- 8527277
TI  - Influence of arterio-venous haemofiltration on teicoplanin elimination.
AB  - The pharmacokinetics of teicoplanin infused for 30 min at a dose of 6 mg kg-1 was
      studied in 11 infected patients under continuous arterio-venous haemofiltration
      (CAVH). Serum teicoplanin levels were assayed by h.p.l.c. over 24 h. After 0.5 h,
      i.e. at the end of the infusion, the mean plasma concentration was 49.6 +/- 15.1
      mg l-1. At the last sampling time (24 h), the mean concentration was 2.6 +/- 1.0
      mg l-1. The concentration of teicoplanin was determined in the haemofiltrates.
      The percentage of the administered dose recovered in the haemofiltrate was low:
      less than 1% for seven patients, between 1.8 and 3.7% for three patients and 7%
      for one patient. CAVH patients should be given teicoplanin using the same dosage
      regimens as previously described for patients with renal impairment.

PMID- 8527278
TI  - Intradermal actions of hypertonic saline involve neural and vascular mechanisms.
AB  - The aim of this study was to investigate whether the wheal and flare responses to
      intradermal injection of hypertonic (4.5%) saline (HTS) were inhibited by local
      injection of 1% lignocaine. Eight normal subjects were studied on one occasion.
      Lignocaine (0.125 ml) was infiltrated at four sites on one forearm and normal
      saline on the other. Five minutes later, duplicate intradermal injections of 30
      microliters of histamine (22.5 nmol ml-1), substance P (1 nmol ml-1), HTS and
      normal saline were given coded and in random order, one of each pair to each
      forearm. Lignocaine inhibited flare responses to histamine, substance P and HTS
      by 56% (P < 0.01), 78% (P < 0.01) and 77% (P < 0.05) respectively suggesting
      similar involvement of an axon reflex. Wheal to histamine was inhibited by 31% (P
      < 0.02) and to substance P by 33% (P < 0.05) but not to HTS. This suggests that
      the mechanism of wheal response to HTS differs from that of histamine and
      substance P.

PMID- 8527279
TI  - Pharmacoeconomics: a challenge for clinical pharmacologists.

PMID- 8527280
TI  - The influence of age, liver size and enantiomer concentrations on warfarin
      requirements.
AB  - 1. We have tested the hypothesis that the fall in hepatic mass with age
      influences the age related increase in sensitivity to warfarin. In 39 otherwise
      healthy outpatients, aged 50-87 years, stabilised on warfarin for prophylaxis of
      thromboembolism, age, mean International Normalised Ratio (INR), and mean
      warfarin dosage were recorded. Liver volume was measured by ultrasound, and
      plasma was assayed for trough concentrations of (R)- and (S)-warfarin. 2. There
      was a negative correlation between age and liver volume (r = -0.41; P = 0.01) and
      age and dose (r = -0.53; P = < 0.001) and a positive correlation between liver
      volume and dose (r = 0.49; P = 0.002). There was no significant correlation
      between dosage and (R)- and (S)-warfarin concentrations, nor between dosage and
      INR. 3. The regression model including both age and liver volume data showed a
      better fit for estimation of warfarin dosage requirement than regression models
      based on age and liver volume data alone. Ninety-five per cent prediction
      intervals for warfarin dose requirements were wide, whether age alone, or age and
      liver volume were used in calculations. 4. Due to inter-individual variation in
      warfarin dosage requirements related to other influences, both explained and
      unexplained, routine measurement of age and liver volume would not contribute
      further clinically useful information to that obtained by the INR test currently
      used for predicting warfarin dosage requirements.

PMID- 8527281
TI  - Stereospecific pharmacokinetics of rac-5-methyltetrahydrofolic acid in patients
      with advanced colorectal cancer.
AB  - 1. The pharmacokinetics and toxicity of racemic 5-methyltetrahydrofolic (rac-5
      MTHF) acid after i.v. infusion were investigated in 18 patients with advanced
      colorectal cancer. Doses of 100-600 mg rac-5-MTHF/m2 were administered over 2 h
      together with a bolus of 500 mg/m2 5-fluorouracil (5-FU) as a midpoint injection.
      2. The pharmacokinetics of both diastereoisomers were linear in the range from
      100-600 mg 5-MTFH/m2. Independent of the administered dose, the maximal plasma
      concentration of [R]-5-MTHF was nearly twice that of [S]-5-MTHF. The elimination
      of [S]-5-MTHF from plasma was considerably faster than that of the [R]-isomer
      (elimination half-life: 3.1 +/- 1.0 h vs 8.3 +/- 3.2 h). No metabolites were
      detected in plasma and in urine samples. 3. The plasma protein binding was
      stereoselective ([R]-5-MTHF bound: 88.2 +/- 2.7%; [S]-5-MTHF bound: 59.9 +/-
      6.8%; P < 0.001), causing a significantly higher renal clearance for [S]-5-MTHF
      when compared with the [R]-isomer (37.5 +/- 23.7 ml min-1 vs 12.7 +/- 11.2 ml min
      1, P < 0.001). There was no dose dependence, but gender influenced renal
      clearance (CLren[R]-5-MTHF: male vs female: 20.5 +/- 14.5 ml min-1 vs 7.8 +/- 4.7
      min-1, P = 0.03; CLren [S]-5-MTHF: male vs female: 57.2 +/- 21.7 ml min-1 vs 25.7
      +/- 16.2 ml min-1, P = 0.006). 4. Toxic side effects of the combination 5-FU/5
      MTHF were rare and generally mild, and included stomatitis, nausea/emesis,
      diarrhoea, anaemia, leukopenia, and thrombocytopenia. 5. In combination with 500
      mg 5-FU/m2 a single dose of 600 mg rac-5-MTHF/m2 can safely be administered to
      patients with colorectal cancer. A similar therapeutic benefit of 5-MTHF to
      folinic acid in the biochemical modulation of 5-FU is supported by the comparison
      of in vitro and in vivo data.

PMID- 8527282
TI  - The accumulation of mercaptopurine metabolites in age fractionated red blood
      cells.
AB  - 1. Red blood cells from four children with lymphoblastic leukemia were age
      fractionated on Percoll density gradients into 'young', 'middle-aged' and 'old'
      cells. 2. The rates of accumulation of the mercaptopurine (MP) metabolites
      thioguanine nucleotides (TGNs) and methylmercaptopurine nucleotides (MeMPs) were
      measured in the cell fractions from the start of MP continuing chemotherapy. 3.
      TGNs and MeMP metabolites were present in all the red cell fractions after 3 days
      oral MP. There was no significant difference between the metabolite
      concentrations measured in either young, middle-aged or old cells (Mann-Whitney P
      = 1.0 to 0.12). 4. These observations suggest that MP metabolites do not enter
      red cells at the stem cell level at the start of therapy. 5. With respect to the
      monitoring of therapy, these results suggest that the concentration of TGNs after
      7 to 10 days MP could be used to predict eventual steady-state concentrations
      using a simple model.

PMID- 8527283
TI  - The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH)
      and a stable analogue, dimethyl proline-TRH, in healthy volunteers.
AB  - 1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue,
      dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were
      assessed in healthy volunteers in two randomised, double-blind, placebo
      controlled crossover studies. 2. Both doses of TRH produced significant but
      transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg,
      1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm
      Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of
      RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start
      of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg
      and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg
      recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8
      mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic:
      8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart
      rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension
      was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were
      noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea,
      acid taste, urethral sensations) and duration of subjective effects.

PMID- 8527284
TI  - Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.
AB  - 1. Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the
      treatment of anxiety disorders, which predominantly affect women of child-bearing
      age. The purpose of the present study was to assess the pharmacokinetics of
      alprazolam and its two hydroxylated metabolites: 4-hydroxy-alprazolam and alpha
      hydroxy-alprazolam in lactating human volunteers and to test the predictability
      of four recently reported models for drug transfer into milk based on
      physicochemical properties. 2. Multiple milk and serum samples in eight lactating
      subjects were collected up to 36 h following single oral doses of 0.5 mg
      alprazolam; suckling of the infant was discontinued after drug administration. 4
      Hydroxy-alprazolam was the predominant metabolite in serum samples while alpha
      hydroxy-alprazolam was not detected. 3. The mean oral clearance of alprazolam was
      1.15 +/- 0.32 ml min-1 kg-1. The time course of alprazolam in milk roughly
      paralleled the perspective plasma time profile (mean serum residence time = 16.42
      +/- 4.69 h; mean milk residence time = 18.93 +/- 7.03 h). The mean terminal half
      life in serum was 12.52 +/- 3.53 h. 4. Observed milk/serum concentration ratios
      were determined in vivo as AUCmilk/AUCserum (mean M/S(obs) = 0.36 +/-
      0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527285
TI  - The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by
      means of the Simeons therapy: a criteria-based meta-analysis.
AB  - 1. A meta-analysis was conducted to assess if there is scientific ground for the
      use of human chorionic gonadotropin (HCG) as adjunctive therapy in the treatment
      of obesity. 2. Published papers relating to eight controlled and 16 uncontrolled
      trials that measured the effect of HCG in the treatment of obesity were traced by
      computer-aided search and citation tracking. 3. The trials were scored for the
      quality of the methods (based on four main categories: study population,
      interventions, measurement of effect, and data presentation and analysis) and the
      main conclusion of author(s) with regard to weight-loss, fat-redistribution,
      hunger, and feeling of well-being. 4. Methodological scores ranged from 16 to 73
      points (maximum score 100), suggesting that most studies were of poor
      methodological quality. Of the 12 studies scoring 50 or more points, one reported
      that HCG was a useful adjunct. The studies scoring 50 or more points were all
      controlled. 5. We conclude that there is no scientific evidence that HCG is
      effective in the treatment of obesity; it does not bring about weight-loss of fat
      redistribution, nor does it reduce hunger or induce a feeling of well-being.

PMID- 8527286
TI  - A comparison of the contractile effects of 5-hydroxytryptamine, sumatriptan and
      MK-462 on human coronary artery in vitro.
AB  - 1. MK-462 (N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H- indol-3
      yl]ethylamine) is a novel selective 5-HT1D-receptor agonist which in clinical
      trials has been shown to be an effective antimigraine agent. As angiographic
      studies have shown that sumatriptan (an established 5-HT1D-receptor agonist) can
      cause coronary artery vasoconstriction in patients, we compared the effects of MK
      462 with those of 5-HT and those of sumatriptan, on isolated segments of human
      coronary artery in vitro. 2. Coronary arteries were obtained from explanted
      hearts from patients (n = 22, 2 females, 20 males, aged 21-60 years) undergoing
      cardiac transplantation. Endothelium-denuded ring segments of coronary artery,
      2mm long were mounted in organbaths for isometric tension recording. For each
      arterial ring segment, a cumulative concentration-effect curve to either 5-HT,
      sumatriptan or MK-462 was determined. After maximal response to each agonist had
      been obtained, ketanserin (a 5-HT2 receptor antagonist) 0.6 microM was added to
      the tissue bath, followed by methiotepin (0.6 microM) and the reduction in
      tension produced by the addition of each antagonist was determined. 3. Out of 22
      coronary arteries studied, only 10 showed any response (contraction) to 5-HT. Not
      all arteries which responded to 5-HT contracted in response to both sumatriptan
      and MK-462 (one ring from each artery being exposed to a single agonist in each
      case).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527287
TI  - Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone
      and single-dose levodopa.
AB  - 1. Single oral doses of the catechol-O-methyltransferase (COMT) inhibitor
      tolcapone (10-800 mg) or placebo were administered simultaneously with a dose of
      levodopa/benserazide 100/25 mg to seven sequential groups of six healthy male
      subjects in a two-way crossover study. 2. Plasma concentrations of tolcapone, its
      metabolite 3-O-methyltolcapone, levodopa and 3-O-methyldopa (3-OMD) were
      determined in conjunction with COMT activity in erythrocytes. 3. The drug
      combination was well tolerated at all dose levels and there were no signs
      indicative of an increase in dopaminergic stimulation. 4. Tolcapone caused a
      rapid and reversible inhibition of COMT activity in erythrocytes in parallel with
      a dose-dependent decrease in the formation of 3-OMD. Tolcapone increased the area
      under the concentration-time curve and elimination half-life of levodopa. The
      maximum effects were obtained at a dose of about 200 mg when both parameters
      increased approximately twofold. The drug had no influence on the maximum
      concentration of levodopa. 5. Tolcapone was rapidly absorbed and eliminated with,
      on average, a tmax of 1.5 h and a t1/2 of 2.3 h. The drug showed dose
      proportional pharmacokinetics, in contrast to 3-O-methyltolcapone whose formation
      was relatively decreased at higher doses. 6. Plasma concentrations of tolcapone
      correlated with inhibition of COMT activity in erythrocytes and suppression of 3
      OMD levels, but not with changes in levodopa pharmacokinetics.

PMID- 8527288
TI  - Differential actions of desipramine on sympathoadrenal release of noradrenaline
      and adrenaline.
AB  - Spillovers noradrenaline (NA) and adrenaline (A) into plasma were examined before
      and after i.v. administration of 0.3-0.5 mg kg-1 desipramine (DMI) in 19 normal
      volunteers. DMI decreased the total body spillover of NA by 20 +/- 4%, but
      increased that of A by 45 +/- 10%. The results indicate differential
      sympathoadrenal actions of DMI, characterized by inhibition of NA release from
      sympathetic nerves and stimulation of A secretion from the adrenals. These
      effects of DMI provide an explanation for some of the cardiovascular
      complications of tricyclic antidepressant therapy and may also help to explain
      how sympathoadrenal function is differentially regulated.

PMID- 8527289
TI  - Stereoselective disposition of ibuprofen enantiomers in human cerebrospinal
      fluid.
AB  - Since both (R)- and (S)-enantiomers of ibuprofen may act on the central nervous
      system, we investigated their plasma and cerebrospinal fluid (CSF) concentrations
      in 46 patients with nerve-root compression pain requiring a lumbar puncture. Each
      patient received an oral dose of 800 mg rac-ibuprofen. A single blood and CSF
      sample was drawn concomitantly from each patient at intervals between 30 min and
      8 h after dosing. Both isomers peaked later in the CSF (3 h) than in the plasma
      (1.5 h). Their CSF concentrations became higher than their concurrent free plasma
      concentrations after 90 min. The estimated elimination half-lives of (R)- and (S)
      ibuprofen were 1.7 h and 2.5 h in plasma and 3.9 h and 7.9 h in CSF,
      respectively. The AUCCSF/AUCplasma ratios (0, 8 h) were 0.009 and 0.015 for the
      (R)- and (S)-forms, respectively.

PMID- 8527290
TI  - Effect of itraconazole and terbinafine on the pharmacokinetics and
      pharmacodynamics of midazolam in healthy volunteers.
AB  - Twelve healthy volunteers were given orally placebo, itraconazole 100 mg or
      terbinafine 250 mg for 4 days. Midazolam 7.5 mg was ingested on the fourth day,
      after which plasma samples were collected and psychomotor performance tests
      carried out for 17 h. Itraconazole increased the area under the midazolam
      concentration-time curve six-fold (P < 0.001), the peak concentration 2.5-fold (P
      < 0.001) and the elimination half-life two-fold (P < 0.001) compared with placebo
      and terbinafine pretreatments. The pharmacokinetic parameters did not differ
      between placebo and terbinafine phases. The higher concentrations of midazolam
      during the itraconazole phase were associated with increased effects. In contrast
      to itraconazole, terbinafine had no effect on midazolam pharmacokinetics and
      psychomotor performance tests were unchanged from placebo.

PMID- 8527291
TI  - Dose proportional pharmacokinetics of alprostadil (prostaglandin E1) in healthy
      volunteers following intravenous infusion.
AB  - Prostaglandin E1 (PGE1) (30, 60, 120 micrograms) was administered by intravenous
      infusion over a 120 min period in an open, three way randomized, cross-over study
      to 12 healthy male volunteers. For the evaluation of PGE1, PGE0 and 15-keto-PGE0,
      blood samples were drawn prior to, during and after the infusion. Analytical
      measurements were performed by gas chromatography/negative ion chemical
      ionization triple stage quadruple mass spectrometry, a highly specific and
      sensitive GC/MS/MS-method. During intravenous infusion of 30, 60 and 120
      micrograms PGE1, endogenous plasma PGE1 concentrations increased from 1.7 +/- 0.8
      to 4.2 +/- 1.1, 6.7 +/- 1.0 and 11.0 +/- 1.9 pg ml-1 respectively. PGE0 plasma
      concentrations increased from endogenous levels of 1.3 +/- 1.0 pg ml-1 to 7.6 +/-
      2.1, 14.1 +/- 3.7 and 28.0 +/- 3.0 pg ml-1 respectively, whilst 15-keto-PGE0
      plasma concentrations increased from endogenous levels of 10.2 +/- 13.9 pg ml-1
      to 99.3 +/- 27.9, 190.4 +/- 52.5 and 357.2 +/- 72.6 pg ml-1 respectively. Within
      the dose range of 30-120 micrograms PGE1 2 h-1 there was a linear increase of
      Cmax and AUC with the dose. The results of the analysis of variance after
      baseline and dose-correction show a 90% confidence interval in the bioequivalence
      acceptance range of 80 to 125%.

PMID- 8527292
TI  - Single dose pharmacokinetics, safety and tolerability of MK-0476, a new
      leukotriene D4-receptor antagonist, in healthy volunteers.
AB  - MK-4076 or sodium 1-(1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)- ethenyl)phenyl) 3-(1
      hydroxy-1-methylethyl)phenyl)propyl)thio)methyl) cycloproprane) acetate is a
      novel, potent, and specific LTD4-receptor antagonist. The safety, tolerability
      and plasma drug profiles of single oral doses of MK-0476 (capsules) were
      evaluated in 18 healthy male volunteers assigned to one of the two parallel 9
      subject panels. Under fasting conditions, increasing single doses of 20 to 800 mg
      were administered in a first part of the study and in a second part, 200 mg MK
      0476 was given either as a solution, under fasting conditions, or as capsules,
      after a standard breakfast. All volunteers completed the study. Side effects,
      reported by the investigator to be related to study drug, were mild and
      transient. No laboratory abnormalities were noted. In the evaluated dose range of
      MK-0476 (20 to 800 mg) the median value of tmax ranged from 2 to 4 h, while the
      apparent t1/2 value averaged 4 to 5 h. The median tmax value of the 200 mg
      capsule dose was not significantly different from the median tmax of the 200 mg
      oral solution dose indicating that neither disintegration nor dissolution is a
      rate-limiting step for the absorption of MK-0476 from capsules. There was a
      statistically significant increase in the AUC (geometric mean ratio of fed/fast
      was 2.52 with 95% confidence interval of 1.25, 5.06) and in Cmax (geometric mean
      ratio of fed/fast was 1.36 with 95% confidence interval of 0.60, 3.04) when MK
      0476 was given together with a breakfast, suggesting an increase in
      bioavailability.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527293
TI  - Determination of the minimum dose of lactose drug carrier that can be sensed
      during inhalation.
AB  - Lactose is commonly used as a carrier for inhaled drugs. Twenty healthy
      volunteers without respiratory symptoms inhaled seven different doses of lactose
      and a placebo (empty) dose through the four place Diskhaler device, in order to
      determine the lowest dose that could be reliably sensed. The minimum dose for
      which all subjects reported taste or feel sensations was 10 mg. This has
      implications regarding the amount of carrier used in future drug delivery
      systems.

PMID- 8527294
TI  - Effects of intradermal injection of atrial natriuretic peptide.
AB  - Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo
      and in vitro but is bronchodilator in humans. The aim of this study was to
      investigate the wheal and flare dose-response to intradermal injection of alpha
      human ANP in normal humans. Eight normal subjects received five 30 microliters
      injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline,
      histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was
      greater but not significantly than that to saline at 1.55 +/- 0.6 (mean +/- s.e.
      mean) compared with 0.42 +/- 0.17 cm2, but much less than to histamine 9.86 +/-
      0.97 or to substance P 12.5 +/- 1.2. Maximum ANP wheal response was significantly
      greater than that to saline at 0.38 +/- 0.08 compared with 0.18 +/- 0.05 cm2
      (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to
      histamine 0.75 +/- 0.06 or to substance P 1.05 +/- 0.08 cm2. No dose-response to
      ANP was demonstrated, though responses to the highest dose differed significantly
      from those to the lowest dose studied. We conclude that human cutaneous responses
      to ANP differ from those of animals and that the skin is less responsive than
      other tissues in humans.

PMID- 8527295
TI  - Tiracizine disposition in healthy volunteers with reference to the debrisoquine
      oxidation phenotype.

PMID- 8527296
TI  - Before and after triazolam: changes in the consumption of hypnotics in Spain.

PMID- 8527297
TI  - GTP-binding proteins and early embryogenesis in Xenopus.
AB  - During early embryogenesis the specification of body axes and the determination
      of cell subtypes proceeds through cell interactions and movements which involve
      the decoding of various signals in a spatial and temporal manner. An increasingly
      abundant literature has revealed the participation of growth factors and their
      receptors in the induction and regionalization of the mesoderm. The question
      therefore arises as to whether other signal transducing systems are expressed and
      play a role in early embryogenesis. In this mini review we describe the main
      developmental events occurring during early embryogenesis in Xenopus and the
      signalling pathways that are potentially involved; we then summarize the major
      properties of heterotrimeric GTP-binding proteins; finally, we present results
      suggesting that heterotrimeric GTP-binding proteins are expressed during early
      embryogenesis and discuss their potential function.

PMID- 8527298
TI  - Role of heterotrimeric G-proteins in epidermal growth factor signalling.
AB  - Since in 1986 it was reported that a pertussis toxin-sensitive substrate was
      involved in the Ca2+ signal induced by epidermal growth factor (EGF) in rat
      hepatocytes, much evidence accumulated to implicate heterotrimeric G-proteins in
      EGF action. EGF can also induce a cyclic AMP signal, but while the generation of
      a Ca2+ signal appears to be quite general in EGF action, the increase in cyclic
      AMP occurs only in few cell types. In non-transformed cell types these effects
      appear to involve G-proteins. EGF not only induces cell proliferation but also
      interacts with hormones in the short-term control of cell function in quiescent
      cells. Most of the known interactions are on cyclic AMP mediated hormone effects,
      and in many cases, the interaction between EGF and hormones involves G-proteins.
      Here we review the evidence accumulated in recent years that implicate G-proteins
      in EGF action. An understanding of the mechanisms involved may reveal new
      mechanisms of G-protein regulation and will contribute to our knowledge of EGF
      function and signal transduction.

PMID- 8527299
TI  - Does nitric oxide play a role in liver function?
AB  - Nitric oxide (NO) is becoming increasingly recognised as a signalling molecule in
      many organs, although its role in the liver remains to be fully elucidated. There
      is no doubt that liver cells can produce NO in response to a variety of stimuli
      including Corynebacterium parvum-infection, lipopolysaccharide (LPS) and a
      variety of cytokines. Within the liver, NO modulates some fundamental
      intracellular functions such as protein synthesis, mitochondrial electron
      transport and components of the citric acid cycle. Intercellular roles for NO in
      the liver may include drug metabolism and blood storage. Also, NO acts to protect
      the liver from immunological damage in models of hepatic inflammation.
      Understanding the role of NO in the liver may provide insight into the
      functioning of this organ in health and disease.

PMID- 8527300
TI  - Unsaturated fatty acids synergistically enhance glucocorticoid-induced gene
      expression.
AB  - Regulation by unsaturated fatty acids of glucocorticoid-sensitive gene
      transcription was studied in HeLa cells transiently transfected with a mouse
      mammary tumour virus-luciferase reporter gene. Arachidonic acid and
      docosahexaenoic acid by themselves had no effect on basal levels of luciferase
      expression. However, they were able to enhance dexamethasone-induced
      transcription by 1.4-2.3 times (25-42 times the control levels) in a dose
      dependent manner (ED50: 18 and 8 microM) for arachidonic and docosahexaenoic
      acid, respectively. The glucocorticoid antagonist RU486 effectively antagonized
      the dexamethasone response as well as the synergistic effect observed in the
      presence of arachidonic and docosahexaenoic acids, suggesting that the
      glucocorticoid receptor was an intermediate in the fatty acid synergism of the
      dexamethasone response. These studies show that fatty acids may be playing a role
      in modulating the intracellular steroid hormone signalling pathway to co-regulate
      a glucocorticoid-sensitive promoter.

PMID- 8527301
TI  - Erythropoietin induces biphasic activation of p70S6k: evidence for a different
      regulation of early and late phase of activation.
AB  - The murine erythroleukaemia cell line HCD-57 proliferates in response to
      erythropoietin. Stimulation of erythropoietin-deprived cells with the cytokine
      induces the phosphorylation and biphasic activation of the 70,000 M(r) S6 kinase.
      Two peaks of enzyme activity were observed after 30 and 120 min, respectively.
      Early and late phase of activation differ in their sensitivity to the protein
      kinase C inhibitor staurosporine suggesting different regulatory mechanisms.

PMID- 8527302
TI  - An inositol phosphoglycan from Trypanosoma cruzi inhibits ACTH action in calf
      adrenocortical cells.
AB  - We describe the effect of an inositol phosphoglycan (IPG) purified from
      Trypanosoma cruzi on the stimulation of aldosterone and cAMP production by ACTH
      in calf adrenocortical cells. T. cruzi IPG has two galactofuranose residues
      (Galf) which are not frequent in other IPGs. The effect of IPG with
      galactofuranose residues (IPG Galf) and IPG without these residues (IPG) was
      investigated. It was found that IPG Galf slightly decreased the stimulation of
      aldosterone and cAMP production by ACTH, whereas IPG significantly inhibited ACTH
      mediated accumulation of both aldosterone and cAMP. The inhibition of aldosterone
      content in ACTH-treated cells by IPG was dose dependent. It was also found that
      the pretreatment of calf adrenocortical cells with IPG inhibited the accumulation
      of aldosterone provoked by ACTH and dibutyryladenosine-3',5'-cyclic monophosphate
      (db-cAMP). On the other hand, the activation of a GPI (glycosyl
      phosphatidylinositol)-phospholipase C by ACTH was evaluated. First it was found
      that the release of ceramide from a GPI-like molecule: a glycoinositol
      phosphoceramide (LPPG) purified from T. cruzi is increased in ACTH-treated cells.
      Second, the release of alkaline phosphatase, a GPI-anchored enzyme, to the
      extracellular medium was increased in these cells by ACTH. These data suggest
      that ACTH activates a phospholipase C in calf adrenocortical cells, releasing
      IPG, which in turn may inhibit, or modulate ACTH action.

PMID- 8527303
TI  - Phorbol ester-dependent regulation of nuclear protein tyrosine phosphatase in
      situ.
AB  - Incubation of splenal lymphocytes with phorbol ester (50 nM PMA) influenced
      nuclear protein tyrosine phosphatase activity in a time-dependent manner. The
      activity was elevated after a short incubation (90 s) but was decreased in
      comparison to untreated cells after 30 and 120 min of incubation. The presence of
      H7 suppressed the changes. Okadaic acid, an inhibitor of protein phosphatases 2A
      and 1, led to a similar increase in the activity of nuclear protein tyrosine
      phosphatase during short-term incubations as phorbol ester but eliminated the
      subsequent activity decrease. Immunoblots revealed that the same amounts of two
      forms (49,000 and 60,000 M(r)) of protein tyrosine phosphatases were present in
      the nuclei from phorbol ester-stimulated and non-stimulated cells. The 60,000
      M(r) form co-migrated with a phosphotyrosine-containing protein. The amount of
      phosphotyrosine was increased in comparison to control cells after 30 min of
      phorbol ester treatment.

PMID- 8527304
TI  - Signal transduction pathways leading to arachidonic acid release from
      neutrophilic HL-60 cells. The involvement of G protein, protein kinase C and
      phospholipase A2.
AB  - Arachidonic acid release from undifferentiated and neutrophilic HL-60 cells was
      studied. In neutrophilic cells it was stimulated by N-formyl-Met-Leu-Phe and
      mastoparan by a mechanism involving Gi protein and phospholipase C and was
      largely dependent on diacyglycerol lipase. Maximum release from both cell types
      was achieved with fluoride and required cellular energy. Inhibitor studies
      suggest that arachidonic acid release by fluoride stimulation leads to
      phospholipase A2 activation with signal transduction involving phospholipase C
      and protein kinase C. Only neutrophilic cells responded to phorbol ester if
      Ca(2+)-ionophore was simultaneously present but this effect was abolished by
      extended treatment with phorbol ester. Thus, protein kinase C plays a major role
      in highly stimulated neutrophilic cells. These cells are differently equipped
      with protein kinase C isoenzymes compared with undifferentiated cells. In
      contrast, both cell types contain similar levels of type II and cytosolic
      phospholipases A2, the former being by far the more prevalent.

PMID- 8527305
TI  - The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase,
      on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and
      DNA synthesis.
AB  - PI 3-kinase, an enzyme that selectively phosphorylates the 3-position of the
      inositol ring, is acutely activated by insulin and other growth factors. The
      physiological significance of PI 3-kinase activation and, more specifically, its
      role in insulin action is an area under intense investigation. In this study, we
      have examined the role of PI 3-kinase activation in mediating selected metabolic
      and mitogenic effects of insulin employing the fungal metabolite wortmannin, a
      potent inhibitor of PI 3-kinase activity. In isolated rat and cultured 3T3-L1
      adipocytes, wortmannin inhibited insulin-stimulated glucose transport (IC50 = 9
      nM) without a significant effect on basal transport. Insulin-stimulated
      translocation of GLUT4 in isolated rat adipocytes was markedly inhibited by
      wortmannin. Wortmannin had no effect on either basal or insulin-stimulated
      glucose utilization in L6 myocytes, a skeletal muscle cell line in which GLUT1 is
      the predominant transporter isoform. Wortmannin also partially antagonized the
      antilipolytic effect of insulin on adenosine deaminase-stimulated lipolysis in
      isolated rat adipocytes. Furthermore, wortmannin caused a significant reduction
      in insulin-stimulated DNA synthesis in Fao rat hepatoma cells. We conclude that
      PI 3-kinase activation is necessary for maximum insulin-stimulated glucose
      transport, translocation of GLUT4, antilipolysis and DNA synthesis.

PMID- 8527306
TI  - Calcium-inducible transmodulation of receptor tyrosine kinase activity.
AB  - Calcium is a potent mitogen and transmodulator of growth factor receptor
      activity, but does not activate tyrosine kinases in ligand-deprived cells
      (Epstein et al. 1992) Cell Growth Different. 3, 157-164). In this study the
      mitogenic and transcriptional effects of increased extracellular calcium and
      ionophore are shown to be identical in 3T3 cells, consistent with mediation of
      these effects via increased intracellular calcium availability. Near-maximal
      mitogenic and transcriptional effects are seen after brief exposure to increased
      extracellular calcium or ionophore, while additive effects occur with co
      administration of calcium and platelet-derived growth factor (PDGF). Exposure of
      PDGF-primed cells to calcium or ionophore is associated with a substantial
      enhancement of receptor tyrosine autophosphorylation which is abrogated by
      calcium channel blockade or intracellular calcium chelation. In contrast,
      pretreatment of quiescent cells with calcium or ionophore significantly
      diminishes subsequent PDGF-inducible receptor autophosphorylation. Intracellular
      calcium thus appears to potentiate the kinase activity of ligand-stimulated PDGF
      receptors while inhibiting ligand-inducible activation of unstimulated receptors.
      These findings suggest a model of receptor tyrosine kinase regulation involving
      calcium-dependent positive and negative feedback loops which vary with the
      activation state of the receptor.

PMID- 8527307
TI  - Double effect of ethanol on intracellular Ca2+ levels in undifferentiated PC12
      cells.
AB  - In PC12, a cellular line derived from a rat pheochromocytoma, ethanol (EtOH)
      induces a different effect depending on the concentration used. When resting
      cells are incubated with an alcohol concentration less than or equal to 120 mM,
      the [Ca2+]i increased with a double phase pattern. If the alcohol concentration
      was increased over 120-160 mM, EtOH reversed its effect and the [Ca2+]i
      decreased. This decrease was strongly inhibited if KCl-depolarized cells were
      used and was completely abolished if the substrate constituted EtOH-chronically
      treated cells. The Ca2+ increase is the consequence of an activation of L-type
      voltage-activated channels, while the other voltage-dependent channels (N-type),
      the receptor-operated channels and the Ca2+ extrusion pump present in these cells
      are not involved in EtOH action. These findings indicate that EtOH can induce (by
      different mechanisms) both potentiating and inhibiting effects on [Ca2+]i in PC12
      cells in relation to the alcohol dose effectively present in the suspension
      medium.

PMID- 8527308
TI  - Biphasic formation of inositol phosphates in opsonized zymosan-stimulated human
      neutrophils.
AB  - Stimulation by serum-opsonized zymosan (SOZ) typically causes a biphasic rise in
      the cytosolic free Ca2+ concentration ([Ca2+]i) of human neutrophils. It consists
      of an initial slow Ca2+ release from internal pools lasting for 60 s, followed by
      a rapid but sustained influx of Ca2+. It was the aim of this study to elucidate
      the underlying mechanism of this atypical Ca2+ response. For this reason we
      analysed the production of inositol phosphates (InsPs) in myo-[3H]inositol
      labelled cells. Stimulation by SOZ within 10 s transiently elevated inositol
      trisphosphate (InsP3) by 1.50-fold. This response was followed by a second, more
      sustained 1.55-fold rise in InsP3 by 90 s. A similar, biphasic pattern of
      inositol tetrakisphosphate (InsP4) formation with 1.15- and 1.35-fold increases,
      respectively, was observed. The SOZ-induced formation of InsP3 was unaffected by
      the removal of extracellular Ca2+ by 1.4 mM EGTA. In contrast, the early
      accumulation of InsP4 was stronger and more prolonged and no second rise over the
      baseline level was seen in the absence of extracellular Ca2+. Under these
      conditions, the sudden exposure of Fura-2 AM loaded, SOZ-stimulated neutrophils
      to extracellular Ca2+ at a time point where InsP4 was the predominant InsP
      resulted in a marked increase in [Ca2+]i. Recalcification at a time point when
      InsP3 was the major InsP had no effect on [Ca2+]i. These findings suggest that in
      SOZ-stimulated neutrophils (1) the transient, first accumulation of InsP3
      mediates the slow Ca2+ release from internal pools, and (2) the second, more
      pronounced formation of InsP4 triggers the Ca2+ influx.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8527309
TI  - Oestradiol-17 beta modulates PAF-evoked phospholipase D activity but not
      inositide-lipid hydrolysis in human endometrial cell line, HEC-1B.
AB  - Platelet-activating factor (PAF) has been shown to stimulate phospholipase D
      (PLD) activity in human endometrium. The effect of 17 beta-oestradiol on PAF- and
      12-O-tetradecanoylphorbol 13-acetate (TPA)-evoked PLD activity assayed as an
      accumulation of [3H]phosphatidylbutanol was examined in [3H]myristic acid
      labelled in a human endometrial epithelial cell line HEC-1B. TPA stimulated PLD
      activity in a dose-dependent manner whereas PAF had no significant effect on PLD
      activity. Following 48 h pretreatment with 100 nM 17 beta-oestradiol, PAF evoked
      PLD activity while leaving inositol trisphosphate accumulation in myo-[2-3H]
      inositol-labelled HEC-1B cells unaffected. In the 17 beta-oestradiol-treated
      cells, TPA-stimulated PLD activity was significantly elevated at 100 nM TPA (P <
      0.05) and 1 microM TPA (P < 0.05) compared to responses in the untreated cells,
      suggesting that 17 beta-oestradiol may upregulate PKC activity. Interestingly,
      following a 30 min pretreatment of HEC-1B cells with a range of 17 beta
      oestradiol concentrations. TPA (10 nM) and PAF (100 nM) stimulated PLD activity.
      However, TPA-stimulated PLD activity levels fell 10-fold while PAF-mediated PLD
      activity remained elevated at 10 nM and 100 nM concentrations of 17 beta
      oestradiol suggesting a different mechanism of activation. These results indicate
      that 17 beta-oestradiol can upregulate PAF-induced PLD activity in HEC-1B cells.

PMID- 8527310
TI  - Role of glycosyl-phosphatidylinositol hydrolysis as a mitogenic signal for
      epidermal growth factor.
AB  - We have investigated the role of the hydrolysis of glycosyl-phosphatidylinositol
      (GPI) as one of the signalling pathways elicited after interaction of epidermal
      growth factor (EGF) with its specific plasma membrane receptor (EGFR). Endogenous
      GPI was characterized in both NIH 3T3 mouse fibroblast cells and in EGFR
      transfected NIH 3T3 cells (designated EGFR T17). GPI molecules isolated from both
      cell lines were identical and they incorporated radioactivity from both sugar and
      fatty acid substrates. Incubation of EGFR T17 cells with EGF, produced a rapid
      and transient hydrolysis of GPI. Maximum hydrolysis occurred after a 1-min
      incubation with 50 nM EGF. No such effects of EGF were observed in the parental
      cell line. Both inositol phosphoglycan (IPG)- and EGF-induced cell proliferation
      was inhibited in the presence of an IPG-antibody to different extents. The
      relationship between GPI hydrolysis and the activity of the EGFR was studied
      using the tyrosine kinase inhibitors tyrphostin (RG50864) and genistein. These
      agents were able to significantly inhibit EGF-mediated cell proliferation, EGF
      dependent hydrolysis of GPI and EGF-regulated autophosphorylation of the EGFR. It
      is concluded that GPI hydrolysis is one of the earliest intracellular events
      generated in response to EGF.

PMID- 8527311
TI  - Ectoprotein kinase activities on non-differentiated and differentiated U-937
      cells.
AB  - Incubation of intact U-937 cells with 1 micron [gamma-32P] ATP resulted in rapid
      (10 min) incorporation of radioactivity into phosvitin, kemptide and protein
      kinase C (PKC)-peptide. The amount of incorporation was dependent on substrate
      type and concentration, and on incubation time. Staurosporine, H-7 and Mg(2+)
      exclusion abolished phosphorylation of kemptide and PKC-peptide but not
      phosvitin. Cyclic AMP and phorbol ester enhanced kemptide and PKC-peptide
      phosphorylation. Protein kinase inhibitor (PKI) inhibits only kemptide
      phosphorylation. Cell differentiation enhanced 2-fold the phosphorylation of
      phosvitin and PKC-peptide without significant effect on kemptide phosphorylation.
      ATP concentrations sufficient to trigger changes in intracellular Ca2+ were
      sufficient to support extracellular phosphorylation reactions. The results
      suggest the presence of at least three ectokinase activities on U-937 cells that
      may play important roles in regulating membrane associated specific functions of
      developing and mature monocytes.

PMID- 8527312
TI  - [Ovarian cysts in childhood].
AB  - It's perform a descriptive study about a series of events with the purpose of
      discover the own characteristics of ovarian cysts and which characteristics
      determine its treatment. In the 41 patients (10 newborn, 14 prepubertal females
      and 17 post-menarchal females) we analyzed their symptoms, pathological findings,
      ecographics details, treatment, diagnostic and follow-up. The predominant symptom
      has been the abdominal pain (18 patients). In 8 newborn the cyst was find before
      born by prenatal sonography. The cyst was palped like abdominal mass in 22
      patients and it was like a picture of acute abdomen in 11. It was found in the
      right ovary in 24 patients and bilaterally in 7. By pelvic ultrasonography was
      observed a superior size of 5 cm of diameter in 28 occasions, in 17 there were
      imagine of complex and in 3 there were hemorrhagic. In 16 patients the suspicion
      diagnostic was of torsion and in 5 of appendicitis. The torsion was confirmed in
      11. In 16 patients it was a follicular cyst, in 9 was a dermoidal and in 9
      hemorrhagic. Was realized a surgical treatment (cystectomy or ooforectomy in 36
      girls, in 4 was realized a puncture and evacuation (bigger of 5 cm with clear
      liquid) and in 7 was hope the spontaneous evolution (clear liquid and infer size
      of 5 cm). There were not relapses. The clinic manifestations are presents with
      own characteristics depending of the cyst affected to newborn, premenarchal or
      menarchal females. The indications of surgery are: symptoms which are not
      resolved after a observation time (24-49 hours) and cysts of big volume
      associated a complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527313
TI  - [Latex allergy in children with spina bifida].
AB  - Latex allergy is a frequent happening in children with spina bifida or congenital
      urologic abnormalities. These patients have multiples exposures to derivatives of
      latex as part of the management increasing the risk of allergic reactions. We
      present three children who developed general anaphylactic reaction during
      urodynamic exploration with a rectal latex catheter. All patients showed positive
      skin test and positive latex specific IgE test (RAST). A prospective survey of 17
      patients with spina bifida at the time of cystometry showed positive RAST levels
      in 7 (41%). Recommendations for prophylaxis are included, suggesting the
      avoidance of latex products in children with spina bifida since birth.

PMID- 8527314
TI  - [Surgery of ectopic ureterocele in children: strategy based on prenatal
      function].
AB  - From 1981 to 1993, we have treated 31 pediatric patients with ectopic ureterocele
      (associated to duplex system, intra and extravesicals). Diagnostic work-up
      included abdominal ultrasound, intravenous urography (IVU), sequence mictional
      cystouretrography (SM-CU) and diuresis renography (DTPA-DMSA o MAG-3). Patients
      were divided in two groups: 1. Good renal function in the affected system (5
      cases) with 2 endoscopic incision of the ureterocele and 3 without surgical
      treatment (all intravesical). 2. Almost non-existent ipsilateral renal function
      (26 cases), treated by heminephrectomy and ureterocelic aspiration, and in the
      remaining a nephrectomy was done for ipsilateral non-existent renal function. 2
      cases treated by endoscopic incision presented vesicoureteral reflux, and 4 cases
      treated by nephrectomy had a low grade reflux. There is no a definite treatment
      established. The choice should by made based on renal function. Endoscopic
      incision is a good choice in obstructed cases with good renal function. In those
      with no function at all, heminephrectomy with aspiration of the ureterocele will
      be the best treatment if we consider that almost 50 percent of the patients will
      need a second surgical procedure.

PMID- 8527315
TI  - [Clinical response of different colonic segments to chemical denervation: an
      experimental study].
AB  - An experimental study in rats with chemical myenteric plexus destruction of
      different segments of large intestine is presented. Forty Wistar rats weighing
      200-250 g were used. Four groups of ten animals each were made. Group I: control;
      group II: myenteric denervation of 4 cm segment of rectosigmoid; group III:
      myenteric denervation of 4 cm segment of descending colon; group IV: myenteric
      denervation of 4 cm segment of transverse colon. Myenteric denervation was
      produced by serosal application of 0.1% benzalconium chloride during 30 minutes.
      Animals were evaluated by clinical parameters (survival, weight change, food
      intake, nutritional state), radiological (barium enema) and histomorphometry.
      Group IV showed the greatest mortality, nutritional deterioration and colonic
      obstruction while the results of group II are similar to control group.

PMID- 8527316
TI  - [Complications in hypospadias repair: 20 years of experience].
AB  - We report a comparative study of the complications in hypospadias repair of 1185
      patients treated in our hospital in the last 20 years. They are divided in three
      well-defined groups: from 1974 to 1981 (265 p.); from 1982 to 1986 (281 p.) and
      from 1987 to 1993 (624 p.). These were the more frequent complications seen: a)
      Early as cutaneous necrosis, a severe complication that had an incidence of 3% in
      the first period. In the second and third period this percentage diminished to
      1.9% and 1.1%, respectively. Only one patient developed a total necrosis of the
      cutaneous island flap that required a new urethroplasty. b) Late: Persistent
      chordee. It was present in 10% of the children in the first period and it was
      secondary to an inadequate release of the chordee and cutaneous necrosis. The
      incidence of the second period was 3.5% and only 2% of patients of the third
      group suffered it because of a non appropriate selection of the surgical
      technique. Fistula. It was the most common complication and it was present in
      18%, 10% and 7.3% of the patients of each period. We think that the introduction
      of the cutaneous island flap procedure helped to the improvement in the rate of
      fistulas. Urethral structure. The incidence was 12% in the first period, 6.5% in
      the second one and it fall down to 4.4% in the third group due to the triangular
      flap of the glans. Megaurethra. The incidence was of 6.8% in the first period,
      6.5% in the second one and only the 2.9% in the last years.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8527317
TI  - [Venography and percutaneous embolization of the spermatic vein with spring coil
      as treatment of the varicocele in childhood].
AB  - The treatment of varicocele is controversial in boys and it is a contributing
      factor to male infertility. Recently it has been proposed that earlier therapy of
      a varicocele during this period may improve the prognosis of infertility. We
      review our experience with the diagnosis and management of left varicocele in 30
      pediatric patients 6 to 15 years old. All patients had clinically palpable
      varicocele. All were managed under local anesthesia by spermatic venography and
      percutaneous transcatheter embolization of the internal spermatic vein with
      spring coils. All achieved satisfactory occlusion, and during the follow up from
      13 years to 9 months there was only one recurrence, noted in a patient 6 months
      after the procedure. Internal spermatic venograms allowed precise coil placement
      relative to collateral veins which could cause recurrence. Complications
      developed were phlebitis of the pampiniform plexus, leading to swelling and
      erythema of the left scrotum and mild flank pain, these symptoms resolved without
      sequelae. This a safe and effective nonsurgical method of obliterating
      varicoceles in children.

PMID- 8527318
TI  - [Capillary testicular hemangioma: a case report].
AB  - Testicular tumors in infants are rare and most of them are malignant. Hemangioma
      of the testis is an extremely rare tumor in infants. We report on an
      intratesticular capillary hemangioma that appeared in a 10 month-old child
      subsequently undergoing orchidectomy and on the patient's evolution at 4 years.
      The histological characteristics showed proliferation of small blood vessels,
      lined with endothelial cells. Mitoses and atypias were not found. Permitting
      differential diagnosis with other vascular tumors: Masson's vegetant
      intravascular hemangio-endothelioma and angiosarcoma.

PMID- 8527319
TI  - [Ascaris volvulus].
AB  - The parasitic disease may be encountered as a surgical entity. A massive
      infestation by Ascaris can produce intestinal obstruction, resulting in the need
      of an immediate surgical response. We present a case of intestinal obstruction
      caused by Ascaris, with a secondary volvulus due to the bolus of worms.

PMID- 8527320
TI  - [Laparoscopic pediatric surgery].

PMID- 8527321
TI  - [Spina bifida: management after 25 years].
AB  - The authors present their experience of 468 patients with spina bifida treated in
      a period of 25 years. They discuss the philosophy of the management of the severe
      neural tube defects based in the follow up of these patients. This attitude is
      based in the prevention that could be: 1) following Smithells theory; 2) trying a
      prenatal diagnostic before 20 weeks of pregnancy, and 3) doing a selection of
      spina bifida that could be operated.

PMID- 8527322
TI  - [Sensibility and specificity of N-myc oncogene with respect to other prognostic
      factors in 15 neuroblastomas].
AB  - Several biologic features of tumor cells correlate closely with a favorable or
      unfavorable outcome. To aid in assessing correlation in the various number of
      prognostic factors including the age, stage, VMA/HVA ratios, and the serum levels
      of NSE and ferritin, the histopathological features, ploidy, partial monosomy for
      the short arm of chromosome 1, and the tumor N-myc gene copy number, are
      examined. We determined the sensitivity and specificity of classical markers
      above the amplification of the N-myc oncogene. A striking new observation is the
      positive correlation between genomic amplification and some prognostic factors
      (stage, ferritin, NSE, pathologic anatomy and 1p deletion.

PMID- 8527323
TI  - [Our experience in the management of portal cavernoma in children].
AB  - The authors present 14 patients affected with portal cavernoma, diagnosed and
      controlled over the last 12 years. The splenomegaly (60%) and the digestive
      hemorrhages (40%) were the initial study causes. The cavernoma appeared
      idiopathic in 10 patients or secondary either to a catheterization of umbilical
      vein (3 cases) or onfalitis (1 case). The first clinical manifestation oscillated
      between the ages of 3 months to nine years. The diagnosis was performed in the
      initial cases (4 cases) using splenoportography (3 cases) and superior mesenteric
      arteriography (SMA) in the other. In the remaining cases the ultrasonography
      together with the endoscopic evidence of the varies backed up the diagnosis.
      Before the intervention, a SMA was performed in all cases. The surgical decision
      was taken with regards to the persistence of the digestive bleeding after the
      start of medical treatment with propranolol, cimetidine, and sucralfate, along
      with the existence of dangerous varices. Eight patients were operated on, two by
      the Warren technique, four by mesocaval jugular graft interposition (MJI) and two
      by azigo portal disconnection (APD). The shunts initially controlled the bleeding
      in all cases. There was one rebleeding instance at eleven months in a patient
      operated on by MJI, and in another by APD. Four patients continue medical
      treatment without problems, and two are free of treatment. Our experience with
      varies sclerosis is limited to two cases, although since the beginning of the
      treatment, one year ago, neither of them has bled.

PMID- 8527324
TI  - The typing of botulinal neurotoxins.
AB  - The serological identification of Clostridium botulinum neurotoxin (BoNT)
      subtypes has shown to be elusive when current standard serologic tests are used.
      Based on (1) the in vivo response expected on quantitative BoNT-antitoxin systems
      and (2) the actual and the hypothetical antigenic makeup of BoNT subtypes, a
      comprehensive method for BoNTs typing is proposed.

PMID- 8527325
TI  - Immunomagnetic separation of Salmonella from foods and their detection using
      immunomagnetic particle (IMP)-ELISA.
AB  - An immunomagnetic particle based ELISA (IMP-ELISA) for the detection of
      Salmonella from foods has been developed using Dynabeads anti-Salmonella (Dynal,
      Oslo, Norway). Appropriate sample preparation protocols to allow rapid detection
      of Salmonella serovariants in processed (powdered egg products) and non-processed
      (raw chicken) samples have been established. Pre-enriched broths of heat
      processed samples likely to harbour only low levels of competitive enteric flora,
      were boiled and used directly for IMP-ELISA. For non-heat processed or raw
      samples likely to contain higher numbers of such competing organisms, live
      Salmonella cells were first isolated by immunomagnetic separation (IMS) from
      standard pre-enrichment broths, and then post-selectively enriched for a short
      time in M-broth followed by boiling before IMP-ELISA. The total assay time
      including sample preparation was under 26 h for both types of procedure, with a
      lower detection limit of 10(5) Salmonella cells/ml of sample. In an evaluation of
      naturally contaminated poultry samples, all 45 of 48 samples previously shown to
      contain salmonellae in a comparison of ISO, IMS-Plating, Salmonella-Tek ELISA
      (Organon Teknika, Inc. Durham, NC) and a modification of the latter based on IMS,
      were identified as positive. None of the other methods gave positives for all 45.

PMID- 8527326
TI  - Capacitance measurement to assess acid-induced injury to Salmonella enteritidis
      PT4.
AB  - Capacitance measurement was compared with colony counting procedures for the
      enumeration and determination of sub-lethal injury of Salmonella enteritidis
      during storage under varied conditions of pH, acidulant and temperature.
      Capacitance monitoring was shown to offer an improved technique for the
      measurement of sub-lethal injury in cell populations. Higher levels of sub-lethal
      injury were detected by the extension of capacitance detection time than were
      indicated by differential colony counts on selective and non-selective media. The
      extension of capacitance detection time noted with sub-lethally injured cell
      populations was shown to be due to an extended lag phase when cells were placed
      in the capacitance growth medium and not the result of delayed detection of the
      growth of a small, uninjured sub-population. Acetic and lactic acids showed both
      greater lethality and greater ability to inflict sub-lethal injury than the
      stronger citric or hydrochloric acid. Sub-lethal injury and lethality were not
      simply related, as little sub-lethal injury was observed with the stronger acids
      even under conditions that were ultimately highly lethal. The results indicate
      that weak organic acids cause more reversible damage to cellular sites prior to
      death: an observation that has implications for choice of resuscitation
      procedures when examining acidified foods.

PMID- 8527327
TI  - Fumonisins B1 and B2 and toxigenic Fusarium strains in feeds from the Spanish
      market.
AB  - Natural occurrence of fumonisins B1 and B2, incidence of Fusarium species, and
      capacity to produce fumonisins by Fusarium isolates, were investigated in 50 corn
      based samples from Spain destined for animal consumption. Forty-four samples
      (88%) were found to be contaminated with fumonisins. The levels of contamination
      were very low, with a mean of 400 ng/g in the samples. We investigated the
      capacity of 11 isolates of Fusarium moniliforme and 19 isolates of F.
      proliferatum to produce fumonisins. All F. proliferatum isolates and 8 out of the
      11 F. moniliforme isolates assayed produced fumonisins on a corn medium. The
      FB1/FB2 ratio in the isolates ranged from 1.1 to 3.5.

PMID- 8527328
TI  - The effect of transient temperatures on the growth of Salmonella typhimurium LT2
      in gelatin gel.
AB  - The growth of colonies of Salmonella typhimurium derived from single immobilised
      cells was studied while subjected to constant and sinusoidally-varying
      temperatures. The bacteria grew in microbiological culture media adjusted to
      different pH and sodium chloride (NaCl) concentration and solidified with gelatin
      that was contained within a cassette formed between sheets of PVC film that
      allowed gaseous exchange. At pH 7.0 and 0.5% (w/v) NaCl and either 12 degrees C
      or 20 degrees C, S. typhimurium grew at a rate similar to that in liquid medium.
      The decrease in growth rate at 20 degrees C at a lower pH or higher NaCl
      concentration was greater in the case of immobilised cells than for cells in
      liquid medium. The change in the numbers of viable bacteria was measured with
      time under sinusoidally-varying temperatures between 4 and 22 degrees C and
      between 12 and 22 degrees C of period in the range 12 to 480 min. The
      experimental growth curves were compared with predictions based on isothermal
      growth in liquid medium. The discrepancies between experiment and prediction were
      greater for gels stressed by NaCl or pH than for gels at pH 7.0 and containing
      0.5% (w/v) NaCl, consistent with the isothermal observations.

PMID- 8527329
TI  - Predicting growth of Brochothrix thermosphacta at changing temperature.
AB  - A dynamic growth model was tested using Brochothrix thermosphacta incubated in
      broth at changing temperatures. The model successfully predicted growth in the
      temperature range 5-25 degrees C when temperature increased or decreased
      gradually and also when temperature underwent frequent sudden changes. When the
      temperature profile contained step changes from 20-25 degrees C to 3 degrees C
      the observed growth curve deviated from that predicted by the model.

PMID- 8527330
TI  - Development of NASBA, a nucleic acid amplification system, for identification of
      Listeria monocytogenes and comparison to ELISA and a modified FDA method.
AB  - NASBA, an isothermal nucleic acid amplification system was used for
      identification of Listeria monocytogenes. A primer set and a species-specific
      probe were selected from the 16S rRNA sequence. The probe was shown to hybridize
      specifically to the amplified single-stranded RNA of L. monocytogenes. No
      hybridization occurred with amplification product of L. seeligeri, L. innocua, L.
      ivanovii, and L. welshimeri. Detection sensitivity for the NASBA assay was
      determined at 10(6) cfu/ml. The possibility of using the NASBA assay for
      detection of L. monocytogenes in foods after a 2-day enrichment procedure was
      explored. NASBA was compared to a modified FDA method and ELISA for detection of
      L. monocytogenes artificially inoculated (1-100 cfu/25 g) in eight food products.
      False-negative results were obtained with the modified FDA method (6.75%). NASBA
      and ELISA were shown in this study to detect the pathogen with equal efficiency
      (no false negative or false positive results). Both methods allowed detection of
      less than 10 cfu/25 g within 3 days but ELISA can only be used for diagnosis of
      Listeria spp. while the NASBA procedure permitted specific identification of the
      human pathogen L. monocytogenes.

PMID- 8527331
TI  - Efficacy of a lactic acid/sodium benzoate wash solution in reducing bacterial
      contamination of raw chicken.
AB  - Raw chicken wings inoculated with Salmonella, Campylobacter jejuni, Listeria
      monocytogenes, Staphylococcus aureus, or Escherichia coli O157:H7 were washed in
      water (control) or a solution of a 0.5% lactic acid/0.05% sodium benzoate (LB)
      (pH 2.64) for 30 min. Viable cells of pathogenic bacteria and naturally occurring
      psychrotrophic bacteria on wings were enumerated after 0, 2, 4, 6, and 8 days of
      storage at 4 degrees C. Lower populations of pathogenic and psychrotrophic
      bacteria were detected on wings immediately after washing with LB compared to
      populations detected on control wings. LB solution was more effective in killing
      Salmonella, C. jejuni, and E. coli O157:H7 than L. monocytogenes, and S. aureus.
      During refrigerated storage, populations of Salmonella, C. jejuni, L.
      monocytogenes, and E. coli O157:H7 decreased significantly on LB-washed wings, as
      compared to populations of respective pathogens on control wings. The growth of
      psychrotrophic bacteria on LB-washed wings was significantly retarded as compared
      to growth on control wings during refrigerated storage. Washing chicken wings
      with a solution containing 0.5% lactic acid and 0.05% sodium benzoate can greatly
      reduce the populations of pathogenic and psychotrophic bacteria, thus enhancing
      safety and extending shelf life.

PMID- 8527332
TI  - Use of left heart bypass in the surgical repair of thoracoabdominal aortic
      aneurysms.
AB  - The purpose of this study was to assess the usefulness of left heart bypass in
      thoracoabdominal aortic aneurysm surgery. Data from 50 patients who underwent
      thoracoabdominal aortic aneurysm repair between July 1987 and October 1993 were
      retrospectively reviewed. In all of them a left heart bypass (left atrium to left
      femoral artery) with a centrifugal pump (without systemic heparinization) was
      used. Patient-, disease-, and operation-related variables were analyzed using
      univariate methods. There were no intraoperative deaths. The in-hospital
      mortality rate was 8% (n = 4). Survival rates were 77% (+/- 6.5) at 2 years and
      62% (+/- 8.7) at 5 years. Renal failure requiring dialysis occurred in five (10%)
      patients and paraplegia in five (10%). Sixteen (32%) patients had respiratory
      insufficiency requiring prolonged (> 8 days) ventilation. After univariate
      analysis, the risk factors for developing a need for postoperative dialysis were
      found to be the preoperative creatinine level (p = 0.002) and the presence of
      preoperative arterial hypertension (p = 0.018). A history of peripheral vascular
      occlusive disease (p = 0.008) was an important risk factor for predicting late
      death. No factors retained significance in the univariate analysis of hospital
      deaths and postoperative paraplegia. Renal and spinal ischemic times were
      substantially reduced in comparison to the theoretic times calculated if cross
      clamping had been used. Bypass-related complications were completely absent. The
      use of a left heart bypass during thoracoabdominal aortic aneurysm surgery may
      not reduce the global complication rate; the results were similar to those
      achieved using simple cross-clamping. However, this technique appears to be the
      method of choice for protecting organ systems at risk during difficult repairs.

PMID- 8527333
TI  - Do collagen-impregnated knitted Dacron grafts reduce the need for transfusion in
      infrarenal aortic reconstruction?
AB  - The purpose of this study was to evaluate the benefits of collagen-impregnated
      Dacron grafts in patients undergoing infrarenal aortic reconstruction. We
      therefore prospectively compared two consecutive series of patients undergoing
      infrarenal aortic reconstruction with Dacron grafts between January 1991 and
      December 1992. The first group (group A) included 83 high-density knitted
      prosthetic grafts (Dialine I), whereas the second included 82 grafts of the same
      type but impregnated with collagen (Dialine II). The two groups were comparable
      with regard to age, sex, and operative risk factors. They were also comparable in
      terms of the proportion of patients with occlusive disease or aneurysms, that is,
      there were 39 and 36 patients with occlusive disease and 44 and 46 patients with
      aneurysms in groups A and B, respectively. The type of bypass was similar in both
      groups with 17 and 19 tubular grafts and 66 and 63 bifurcated grafts being
      inserted in groups A and B, respectively. Thirteen parameters were studied and
      compared within each group including (1) number of infected grafts, (2) number of
      postoperative occlusions, (3) maximum postoperative temperature, (4) number of
      positive postoperative blood cultures, (5) number of postoperative deaths, (6)
      intraoperative and (7) postoperative quantities of blood transfused, (8)
      difference between pre- and postoperative hemoglobin concentrations, (9)
      difference between pre- and postoperative fibrinogen levels, (10) difference
      between pre- and postoperative platelet counts, (11) duration of aortic clamping,
      (12) date of return of intestinal function, and (13) mean duration of pre- and
      postoperative hospital stays.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527334
TI  - The occluded renal artery: an ongoing surgical challenge.
AB  - Nephrectomy and revascularization are currently the preferred options in the
      management of the chronically occluded renal artery in patients with renovascular
      hypertension or renal insufficiency. We review our experience with these two
      options including early and late functional outcome. Between December 1982 and
      August 1993, chronic occlusion of the main renal artery was documented in 30
      patients. Patients were categorized with respect to surgical intervention: group
      I underwent nephrectomy (on the occluded side) plus contralateral
      revascularization and group II underwent revascularization of the occluded renal
      artery. The median age at the time of operative intervention was 63 years; 53% of
      the patients were women and 47% were men. Hypertension was poorly controlled (>
      or = 3 medications) in 19 patients, and the preoperative serum creatinine level
      was > 1.8 mg/dl in 24 patients (mean 2.6 +/- 1.4 mg/dl). There were 16 patients
      in group I and 14 patients in group II, and there were no perioperative deaths.
      Estimated glomerular filtration rate (> or = 7 days after operation) was either
      unchanged or improved in 15 of 16 patients in group I and in 13 of 14 in group
      II, one of whom became dialysis dependent. Follow-up data were available for 25
      of 30 (83%) patients (mean 45 months; range 1 to 108 months). Excluding one early
      failure, 10 of 13 patients in group I and 7 of 11 in group II did not have end
      stage renal disease at last follow-up. Overall, hypertension was cured or
      improved in 16 of 21 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527335
TI  - Coarctation of the abdominal aorta.
AB  - Four patients with suprarenal coarctation of the abdominal aorta were managed
      from 1978 to 1993 (mean follow-up 8.75 years). Ages at the time of diagnosis were
      2 months, 8 months, 4.5 years, and 15 years, respectively. Three children
      presented with severe hypertension, two of whom were in congestive heart failure,
      and the fourth child presented with a cold, ischemic leg. The 8-month-old patient
      had Williams syndrome (supravalvular aortic and pulmonic stenosis, bilateral
      renal artery stenosis and celiac artery occlusion, "elfin" facies, and mental
      retardation) and was treated nonoperatively. After 12 years of follow-up, he was
      given five medications to control hypertension, cardiac arrhythmias, and heart
      failure. Three patients with abdominal aortic coarctation were treated
      operatively and none died. Two patients underwent bypass grafting from the
      supraceliac aorta to the infrarenal aorta, with bilateral renal artery
      reconstruction in one. Postoperative arteriograms obtained 1 year or more after
      operation were normal in both cases. The 2-month-old patient underwent patch
      aortoplasty, with subsequent reoperation 1.5 years later for recurrent
      hypertension and heart failure with a bypass graft to the left kidney and removal
      of an infarcted right kidney. In all three patients, operative repair of the
      suprarenal aortic coarctation has resulted in long-term control of blood pressure
      and cardiac and renal function.

PMID- 8527336
TI  - Intraoperative determination of intestinal viability by pulse oximetry.
AB  - The utility of transserosal photoplethysmographic pulse oximetry (PO) to assess
      intestinal viability intraoperatively was evaluated using an experimental canine
      model. Comparisons of PO were made with continuous-wave Doppler ultrasound (CWDU)
      and fluorescein (FL) using histopathologic examination for control. Clinical
      examination estimates were included for reference. Four 20 cm portions of small
      bowel from each of four dogs were made ischemic by mesenteric ligation. Thus 320
      individual 1 cm bowel segments were studied by means of PO, CWDU, FL, and control
      histologic grading for ischemia. Statistical analysis revealed no significant
      differences, with PO matching CWDU and FL in intraoperative assessment of small
      bowel viability. PO, which is readily available in most operating rooms, is a
      simpler method than CWDU or FL for assessing intestinal viability. This technique
      is operator independent, easy to interpret and repeat, and is well tolerated. PO
      is the preferred alternative for objective intraoperative assessment of
      intestinal viability.

PMID- 8527337
TI  - Acute popliteal arterial injury: the role of angioscopy.
AB  - Accurate identification of arterial injury in the emergency setting constitutes
      one of the essential prognostic factors in patients presenting with acute
      popliteal arterial injury (APAI). The modalities of angioscopy performed
      intraoperatively by the vascular surgeon, including the details of how angioscopy
      can contribute to therapeutic decisions in this setting, are presented. Between
      June 1987 and August 1993, 26 patients presenting with 27 APAIs (one patient had
      a bilateral APAI) were treated at our institution. Eighteen (67%) lesions were
      due to closed trauma, three (11%) to shotgun pellets, three (11%) to knife
      wounds, two (7%) to iatrogenic wounds, and one (4%) to a bullet wound. Between
      June 1987 and January 1992 (group I, n = 20), treatment consisted of 15 (75%)
      saphenous vein bypasses and five (25%) local repairs. Pre- or intraoperative
      arteriograms were obtained in 14 (70%) cases. Three (15%) major amputations were
      required after popliteal reconstruction. Between February 1992 and August 1993
      (group II, n = 7), two (29%) saphenous vein grafts and five (71%) local repairs
      were performed after routine intraoperative angioscopy. Arteriograms were
      obtained in six (86%) instances. No amputations were necessary in this group. As
      a complement to arteriography, intraoperative angioscopy can determine the extent
      and number of injuries, provides direct visualization of the intima of the entire
      femoropopliteal artery, even when the latter is obscured by thrombus, and ensures
      a final control of popliteal artery repair at completion. After angioscopy, local
      repair was possible more often (71% vs. 25%, p = 0.03) and treatment was
      associated with a better functional result (0% vs. 15% amputation rate, p = 0.04)
      in group II.

PMID- 8527338
TI  - Differential effect of the retropleural and retroperitoneal environments on
      healing of the inner wall of porous fabric prostheses in the thoracic and
      abdominal aorta of the same dog.
AB  - Healing of the inner wall of the same preclotted knitted Dacron arterial
      prostheses was compared in the descending thoracic aorta (DTA) and the abdominal
      aorta (AA) of the same dog. Each of 16 dogs received this dual implantation with
      study periods of 4 weeks for five dogs, 8 weeks for five dogs, and 16 weeks for
      six dogs. Healing was studied with light microscopy, scanning electron
      microscopy, transmission electron microscopy, and immunocytochemistry
      identification. The outer capsule was firmly adherent to the Dacron framework of
      all grafts implanted in the DTA; advanced healing of the inner wall of all
      thoracic grafts was present by 4 weeks, nearly complete healing by 8 weeks, and
      complete healing by 16 weeks. In contrast, the outer capsule was either not
      attached or only loosely adherent to the Dacron framework in eight AA grafts
      (50%), and in these implants no healing of the inner wall occurred beyond the
      limited perianastomotic pannus zone. In the other eight implants in which the
      outer capsule was firmly adherent to the Dacron framework, healing was roughly
      comparable to that in the grafts implanted in the DTA. This study demonstrated
      that (1) DTA grafts heal faster and more completely than AA grafts, (2) healing
      and endothelialization are related to the tightness of the outer capsule, (3)
      there is a high incidence of loose tissue attachment in the AA, and (4) healing
      of aortic grafts is site specific.

PMID- 8527339
TI  - Surgical management of infected PTFE hemodialysis grafts: analysis of a 15-year
      experience.
AB  - The records of 52 consecutive patients who underwent surgical treatment for 57
      episodes of hemodialysis graft infection (HGI) from 1977 to 1993 were reviewed to
      determine the mortality and morbidity associated with this complication and to
      clarify guidelines for its management. The study group consisted of 35 women and
      17 men whose mean age was 57 years at initial graft placement. Thirty-three (58%)
      HGIs involved straight grafts in the upper arm, 12 (21%) straight forearm grafts,
      11 (19%) loop forearm grafts, and 1 (2%) a loop groin fistula. All of these
      grafts were constructed with polytetrafluoroethylene (PTFE). All 57 cases of HGI
      showed at least local evidence and 41 (72%) caused systemic symptoms. Thirty
      seven (65%) HGIs were associated with positive blood cultures. The predominant
      infecting organism was Staphylococcus, which was isolated alone or in combination
      with other organisms from 40 (70%) graft or would sites. Seventy-eight percent
      (31/40) of the staphylococcal infections involved Staphylococcus aureus. The
      median time from graft implantation to diagnosis of HGI was 7 months (mean 16
      months, range 0 to 77 months) and from diagnosis to surgical treatment, 4 days
      (mean 6 days, range 0 to 26 days). Initial surgical management consisted of
      complete excision of all prosthetic material in 43 (75%) cases and partial
      excision in 14. The 30-day mortality rate following the last operation for the
      treatment of HGI was 12% (6/52) and was not significantly increased by incomplete
      excision. Six (86%) of the early deaths were related to sepsis and each of these
      patients had positive blood cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527340
TI  - Aortoiliac bypass in a renal transplant patient using a new technique.
AB  - There are only 18 patients described in the English literature who had a
      preexisting renal transplant and underwent aortic surgery for aortoiliac
      occlusive disease. We describe an additional patient who was treated with a new
      technique using a Sundt shunt and a GraftAssist. This technique provides
      antegrade flow and minimal ischemic time and avoids exploration of arteries not
      involved in the anastomosis.

PMID- 8527341
TI  - Open operative balloon angioplasty of the internal carotid artery: a technique in
      evolution.
AB  - Open operative balloon angioplasty is a treatment alternative for certain
      nonatherosclerotic lesions of the internal carotid artery (ICA) including
      fibromuscular dysplasia (FMD). Standard operative exposure of the carotid
      bifurcation is performed with atraumatic passage of a guidewire and balloon
      through a carotid bulb arteriotomy. Under direct fluoroscopic guidance, precise
      dilatation of the involved area is possible with minimal risk of intimal
      tear/flap or distal embolization as compared with graduated intraluminal
      dilatation or percutaneous balloon angioplasty. Vascular control of the common
      and external carotid arteries lessens the risk of embolization resulting from the
      constant backflow of blood through the ICA before, during, and after balloon
      angioplasty, adding to the overall safety and efficacy of the procedure. We
      report a case of asymptomatic critical carotid artery stenosis associated with
      FMD successfully treated with open operative balloon angioplasty and review the
      current literature regarding treatment options for FMD of the ICA.

PMID- 8527342
TI  - Ruptured ulnar artery pseudoaneurysm.
AB  - Ulnar artery aneurysms and pseudoaneurysms are rare lesions that usually occur
      distal to the wrist and cause symptoms as a result of embolization and not
      rupture. An elderly woman presented with acute rupture of an ulnar artery
      pseudoaneurysm proximal to the wrist, which caused severe neurologic compromise
      as a result of bleeding into Guyon's canal and the carpal tunnel. The patient had
      a remote wrist fracture resulting in a deformity that allowed the ulnar head to
      be in proximity to the ulnar artery. Rupture of the volar capsule with chronic
      abrasion of the artery eventually led to pseudoaneurysm formation and subsequent
      rupture. Emergency operative treatment with excision of the pseudoaneurysm, ulnar
      artery ligation, and repair of the volar capsule resulted in complete neurologic
      recovery without vascular compromise. This case is unique because of the proximal
      location of the pseudoaneurysm and the presentation with rupture. The anatomy,
      pathogenesis, and treatment options are discussed. Excision of the pseudoaneurysm
      with repair of the torn volar capsule is recommended to avoid recurrent problems.
      Vascular reconstruction is needed in cases where radial arterial flow is
      inadequate.

PMID- 8527343
TI  - Thrombolysis to treat arterial thrombotic complications of heparin-induced
      thrombocytopenia.
AB  - An 80-year-old man with diabetes developed acute ischemia of the right leg
      secondary to heparin-induced thrombocytopenia while being treated for a pulmonary
      embolism. For fear of recurrent thrombosis at the operative site, he was treated
      with cessation of heparin, placement of a Greenfield filter, and intra-arterial
      infusion of urokinase into the popliteal artery for 36 hours. All arterial
      thrombus resolved with no complications. One week later he underwent a below-knee
      popliteal to anterior tibial artery translocated cephalic vein bypass and
      transmetatarsal amputation for progressive gangrene of the right toes. The graft
      remains patent 2 years later. This patient represents the eighth case reported in
      the world literature in which thrombolytic therapy was used to treat arterial
      thrombotic complications of heparin-induced thrombocytopenia. Five patients were
      successfully treated without complications, two others required major
      amputations, and one died of adrenal hemorrhage. Although thrombolytic therapy
      should be used cautiously for treatment of arterial thrombotic complications of
      heparin-induced thrombocytopenia, this adjunct may prove useful and safe in
      selected cases.

PMID- 8527344
TI  - Minimally invasive surgery for primary varicose veins: limited invaginated axial
      stripping and tributary (hook) stab avulsion.

PMID- 8527345
TI  - Diagnosis of vascular trauma.

PMID- 8527346
TI  - A two-stage estimation of structural equation models with continuous and
      polytomous variables.
AB  - This paper develops a computationally efficient procedure for analysis of
      structural equation models with continuous and polytomous variables. A partition
      maximum likelihood approach is used to obtain the first stage estimates of the
      thresholds and the polyserial and polychoric correlations in the underlying
      correlation matrix. Then, based on the joint asymptotic distribution of the first
      stage estimator and an appropriate weight matrix, a generalized least squares
      approach is employed to estimate the structural parameters in the correlation
      structure. Asymptotic properties of the estimators are derived. Some simulation
      studies are conducted to study the empirical behaviours and robustness of the
      procedure, and compare it with some existing methods.

PMID- 8527347
TI  - Heretical report on the efficacy of blood pressure treatment in a population
      setting.

PMID- 8527349
TI  - A double-blind comparison of once-daily metoprolol controlled-release and
      atenolol in the treatment of Chinese patients with mild to moderate hypertension.
AB  - The efficacy and tolerability of controlled-release metoprolol (metoprolol
      CR/ZOK), 100-200 mg, and atenolol, 50-100 mg, once daily was compared in Chinese
      patients with mild to moderate essential hypertension. The study was of a
      randomized, double-blind, two-way crossover design. The active treatment periods
      lasted 4 weeks each and were preceded by a 4-week placebo run-in period. The two
      double-blind phases were separated by a 2-week washout period on placebo. Blood
      pressures and heart rates were measured at rest in each 2-week visit and during
      exercise at the end of each treatment period. Twenty-four patients (M/F = 14/10)
      were valid for efficacy analysis. Their ages ranged from 39 to 68, with a mean of
      53.5 years. The rest supine blood pressure and heart rate before active treatment
      was 160 +/- 15/106 +/- 6 mmHg and 75 +/- 14 beats/min (mean +/- SD),
      respectively. A responder was defined as exhibiting a supine diastolic blood
      pressure < or = 90 mmHg or a supine diastolic blood pressure reduction of at
      least 10% of the baseline level. Both agents had high response rate: 88% and 92%
      of all patients responded to metoprolol CR/ZOK and atenolol, respectively. Both
      active treatments considerably reduced resting systolic and diastolic blood
      pressures and heart rates as compared with baseline (p < 0.001), respectively.
      With controlled-release metoprolol, a more pronounced beta 1 blockade was
      obtained than with atenolol, which was expressed as a significant reduction in
      exercise-induced heart rate at the highest comparable workload compared with
      placebo (p < 0.05). These findings are compatible with those reported from
      western populations.

PMID- 8527350
TI  - Changes in urinary enzyme levels following the use of antihypertensive agents in
      patients with essential hypertension.
AB  - When choosing antihypertensive agents for the treatment of hypertension, it is
      necessary to consider the predisposition of individuals to renal damage, which
      may be associated with the long-term effect of such agents. In this respect, this
      study examined the effect of two commonly used antihypertensive drugs (Brinerdin
      and Minizide) on renal function over 24 months in patients diagnosed as having
      essential hypertension. We utilized urinary enzyme studies, which are indicators
      of subtle renal dysfunction. Other parameters of glomerular and tubular function
      were also determined in the pretreatment period, as well as during and at the end
      of treatment of 28 patients (16 males and 12 females) with therapeutic doses of
      Brinerdin and 22 patients (12 males and 10 females) with conventional doses of
      Minizide. During the follow-up period, blood pressure (BP) fell from a mean of
      160/108 +/- 9/4 (SD) mmHg to 130/90 +/- 7/4 on Brinerdin and from a mean of
      160/106 +/- 5/2 (SD) mmHg to 130/90 +/- 8/5 on Minizide. There was no significant
      difference in the levels of BP between the patients taking Minizide and those
      taking Brinerdin before, during, and at the end of treatment. Significant
      elevation (p < 0.05) of the levels of urinary protein, lactate dehydrogenase
      (LDH), and N-acetyl-B-D-glycosaminidase (NAG) was observed in patients on
      Minizide during treatment, and these levels remained elevated during the latter
      part of the study. Normotensive, untreated, age- and sex-matched control subjects
      showed no such urinary parameter changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527348
TI  - Alterations in sodium metabolism as an etiological model for hypertension.
AB  - An adequate matching for race, sex, stage of the menstrual cycle, family history
      of hypertension, and the amount of sodium and other electrolytes in the diet
      should be a prerequisite for valid conclusions when interpreting the erythrocyte
      concentration and fluxes of sodium in essential hypertensive patients in
      comparison with normal subjects. Alterations in intracellular sodium
      concentration and transmembrane sodium transport systems as causes of essential
      hypertension are postulated. This review article describes how this abnormal
      sodium and calcium metabolism translates into increased systemic vascular
      resistance through altered vasoactive responses and/or vasculature structural
      changes.

PMID- 8527351
TI  - Comparison of the efficacy and safety of once-daily versus twice-daily
      formulations of diltiazem in the treatment of systemic hypertension. The Canadian
      Multicenter Diltiazem-CD Hypertension Trial Group.
AB  - The efficacy and safety of optimally titrated once-daily (CD) and twice-daily
      (SR) diltiazem were compared in 111 patients with mild to moderate systemic
      hypertension [seated diastolic blood pressure (DBP) > or = 95 mmHg and < or = 114
      mmHg] in a multicenter, randomized, double-blind, placebo run-in, parallel-group
      trial. Following a 4 week washout and placebo-controlled run-in period, patients
      were randomized to receive diltiazem CD 180 mg and matching placebo (n = 54), or
      diltiazem SR 90 mg bid (n = 57). Total daily doses were titrated from 180 mg to
      360 mg to achieve a goal of seated DBP < 90 mmHg during a 6 week titration
      period. The patients continued to receive their optimal dose for a 6 week follow
      up period. Ninety-six (96) patients (diltiazem CD: 47, diltiazem SR: 49)
      completed the study protocol, with 60% of the diltiazem CD and 55% of the
      diltiazem SR patients achieving the goal of seated DBP of < 90 mmHg (p = 0.685).
      Although significant decreases occurred in seated and standing measurements of
      diastolic and systolic BP and heart rate with treatment in both groups, there
      were no significant differences between treatment groups. Both medications were
      well tolerated, with a similar frequency of adverse effects [diltiazem CD: 24/54
      (37%) patients; diltiazem SR: 24/57 (42.1%) patients] with the most frequently
      reported adverse effects being headache and edema.

PMID- 8527352
TI  - Long-term effects of brief antihypertensive treatment on systolic blood pressure
      and vascular reactivity in young genetically hypertensive rats.
AB  - Recent studies have shown that angiotensin converting enzyme (ACE) inhibitor
      treatment in young spontaneously hypertensive rats (SHR) reduces blood pressure
      into adulthood. This study explored changes in vascular reactivity in adult
      normotensive (WKY) rats and stroke-prone SHR (SHRSP) receiving the following
      treatments at 6-10 weeks of age: (a) ACE inhibitor (ramipril); (b)
      hydralazine/hydrochlorothiazide (hydral/HCTZ); or (c) no treatment. The
      hypothesis tested was that vascular changes and blood pressure would be reduced
      in adult SHRSP treated with ramipril during development. At 17 weeks of age, rats
      were anesthetized and vascular tissue was excised. Isolated experiments in the
      aorta included characterization of initial phasic and tonic contractions to 0.1
      microM angiotensin II (AII). A phenylephrine (PE) concentration-response curve
      was performed on carotid arteries, and threshold values were determined. All WKY
      groups showed lower systolic blood pressure (131 +/- 4 mmHg) and reduced phasic
      AII induced contraction (7.4 +/- 4.7%) compared with SHRSP (217 +/- 4 mmHg; 37.2
      +/- 4%). Antihypertensive treatment reduced blood pressure (ramipril: 168 +/- 2;
      hydral/HCTZ: 198 +/- 6 mmHg) but not phasic AII responses in adult SHRSP; adult
      WKY rats were unaffected by treatment. Threshold values for PE in carotid
      arteries were lower in SHRSP than in WKY, indicating increased sensitivity.
      However, SHRSP treated with ramipril did not demonstrate increased sensitivity to
      PE. These data support the hypothesis that blood pressure and sensitivity to PE
      but not contractile responsiveness to AII in adult SHRSP are determined by an AII
      sensitive mechanism during development.

PMID- 8527353
TI  - Clinical acceptability of ACE inhibitor therapy in mild to moderate hypertension,
      a comparison between perindopril and enalapril.
AB  - The aim of this 3-month double-blind study was to assess the antihypertensive
      effect and acceptability of perindopril in comparison with enalapril in patients
      with mild to moderate essential hypertension. After a 4-week placebo run-in
      period, 161 patients with supine diastolic blood pressure (DBP) between 95 and
      115 mmHg were randomized to receive perindopril 4 mg or enalapril 10 mg once
      daily. If supine DBP was higher than 90 mmHg, treatment was adjusted monthly,
      first by doubling the dose and then by addition of hydrochlorothiazide 12.5 mg.
      After 3 months of active treatment the decrease in supine and standing blood
      pressures was statistically significant within both groups but was not
      statistically different between groups. The percentage of patients (65%) who
      achieved supine DBP of < or = 90 mmHg in the perindopril group was not
      significantly different from the enalapril group (73%). Monotherapy resulted in
      control of supine DBP in 56% of the perindopril group and 58% of the enalapril
      group; the addition of hydrochlorothiazide resulted in control of supine DBP in
      6% and 15% respectively. The number of withdrawals for adverse events was
      statistically significant between groups (0 in the perindopril group and 7 in the
      enalapril group, p = 0.01). During active treatment the most frequently reported
      complaints were headaches and cough; there was not statistically difference
      between groups. Changes in laboratory parameters were minor and not significantly
      different between the two groups except for serum glucose, potassium, and
      triglyceride levels. In conclusion, there was no significance between perindopril
      and enalapril in terms of efficacy. Clinical acceptability seems to be better in
      the perindopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527354
TI  - Long-term antiarrhythmic efficacy and safety of d-sotalol in patients with
      ventricular tachycardia and a low ejection fraction.
AB  - Since in patients with ventricular tachycardia (VT) and compromised left
      ventricular function, antiarrhythmic therapy poses a particular problem, an open
      label safety study of d-sotalol, a new class III antiarrhythmic agent, was
      performed. Thirteen patients with defined VT and a low left ventricular ejection
      fraction (LVEF) were treated with orally administered d-sotalol, 100 mg bid, and
      in a few patients 100 mg tid, in an open study. Patients were followed up for 35
      +/- 11 months, with the longest follow-up amounting to 51 months. The data
      obtained suggest that d-sotalol was moderately effective as an antiarrhythmic
      agent, in particular with respect to premature ventricular contractions (PVCs)
      and coupled and repetitive PVCs. The beneficial effect appeared to persist on
      long-term treatment. d-Sotalol was well tolerated and no subjective or objective
      adverse reactions were observed. There were no signs of worsening of congestive
      heart failure, proarrhythmogenic activity, or torsades de pointes, although QT
      prolongation was observed. There were no dropouts in the study. Two patients
      died: One patient with idiopathic dilated cardiomyopathy (with LVEF = 11%) died
      suddenly after 38 months of follow-up and one patient after 17 months from
      recurrent myocardial infarction. Neither of these had shown recurrence of VT on
      24 hour ambulatory ECG recordings. In conclusion, in this small group of patients
      d-sotalol appeared to be safe and well tolerated during long-term treatment of
      patients with VT and poor left ventricular function. There were clear suggestions
      of antiarrhythmic activity, reflected by the suppression of complex ventricular
      arrhythmias and by the absence of recurrent VT on long-term follow-up in the
      majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527355
TI  - Interactions of a new beta-blocker, celiprolol, with the calcium antagonists,
      diltiazem and nifedipine, on atrioventricular conduction.
AB  - The influence of a new beta-blocker, celiprolol, on the direct dromotropic
      effects of the Ca antagonists, diltiazem and nifedipine, on atrioventricular (AV)
      conduction was estimated in the canine isolated, blood-perfused AV node
      preparation. Diltiazem (1-10 micrograms) and nifedipine (0.3-3 micrograms)
      injected i.a. into the AV node artery dose dependently prolonged the atrio-His
      (AH) interval (5-39 msec and 7-51 msec) in the AV mode preparation. When
      celiprolol (1 and 10 mg/kg) was given i.v. in the support dog, the AH interval in
      the AV node preparation was transiently shortened and then maintained constant as
      a control. These doses of i.v. celiprolol completely abolished the isoproterenol
      induced decrease in the AH interval (28 msec at 0.03 microgram, i.a.) and AV
      nodal tachycardia. In the presence of celiprolol, the same doses of i.a.
      diltiazem and nifedipine increased the AH interval by the same amounts (6-43 msec
      and 8-53 msec) as the control. The incidence of second degree AV conduction block
      produced by diltiazem (2 in 5 AV node preparations at 10 micrograms) and
      nifedipine (2 in 6 preparations at 3 micrograms) was not changed by celiprolol.
      In the second experiments, diltiazem (30-300 micrograms/kg) and nifedipine (3-30
      micrograms/kg), given i.v. in an open-chest in situ vagotomized dog, dose
      dependently increased AV conduction time (AVCT; 2-30 msec and 1-12 msec).
      Celiprolol 1 and 10 mg/kg i.v., which suppressed the isoproterenol-induced
      decrease in AVCT (32 msec at 0.3 mu/kg i.v.) and AV nodal tachycardia (4 in 6 in
      situ hearts), potentiated the prolongation of AVCT by the same doses of diltiazem
      (11-50 msec) and nifedipine (3-40 msec). The incidence of second degree AV
      conduction block produced by i.v., diltiazem (1 in 5 in situ hearts at 300
      micrograms/kg) and nifedipine (0 in 6 in situ hearts at 30 micrograms/kg) was
      aggravated (4 in 5 and 3 in 6 in situ hearts) after i.v. celiprolol. These
      results indicate that although celiprolol does not affect the direct negative
      dromotropic effects of the Ca antagonists, AV block could easily be produced when
      celiprolol eliminates tonic adrenergic influences in vivo.

PMID- 8527356
TI  - Metabolic effects of isradipine in non-insulin-dependent diabetes mellitus
      (NIDDM) hypertensive patients.

PMID- 8527357
TI  - The paradoxical power of the depressed patient: a problem for the ranking theory
      of depression.
AB  - The social ranking (or social competition) theory of depression suggests that the
      capacity for episodes of depressed mood evolved as a mechanism for inhibiting
      challenge. Depressed mood induces the sufferer to accommodate to low social rank,
      or to losing in social competition, or to adopting the one-down position in a
      complementary relationship (Price, 1991; Price, Sloman, Gardner, Gilbert & Rohde,
      1994; Sloman, Price, Gilbert & Gardner, 1994). Thus depressed patients should be
      observed to forego the privileges of high rank and of winning, such as exercising
      social power and getting their own way. However, several commentators have noted
      that depressed patients often seem to be very powerful, and even appear to use
      their depression to manipulate others. This paper attempts to reconcile the
      theory to such observations.

PMID- 8527358
TI  - A clinical concept of the self: the experiential being.
AB  - This paper proposes a clinical concept of the self as experiential being. Such a
      concept offers the triple advantage of being non-reductive, introducing
      experience as a clinical unit of analysis and intervention, and viewing a
      representational capacity to experience as a crucial element towards the
      construction of 'T'. The central importance of 'experience' in health and
      disorder is addressed, followed by a characterization of the processes of 'going
      through', the integration of 'experience' into 'I' and the processes of defence,
      which are viewed from the perspective of the experiential being. Experience, or
      'going through', has five defining characteristics: awareness, motivation,
      linking, learning and evolution. The processing of 'experience' on two levels,
      the representational level and the level of the experimental being, leads to the
      integration of experience into "I'. The owning of experience, and not defence, is
      seen as the key factor in health and disorder. As the capacity to own experience,
      which includes the owning of defence, is the key to the road to health, it is
      argued that clinical intervention must focus on the person's capacity to own all
      his or her experiences.

PMID- 8527359
TI  - Transpersonal processes: a bridge between object relations and attachment theory
      in normal and psychopathological development.
AB  - This paper has three aims: (a) to present the further development of the concept
      of transpersonal processes and the bimodal theory of relational cognition; (b) to
      show how the bimodal concept illuminates developmental theory and facilitates the
      move from object relations theory toward a relational systems model; and (c) to
      show how the attachment paradigm and the notions of internal working models
      (Bowlby, 1973) and self-reflective capacity (Fonagy, 1991) are both congruent and
      synergistic with the transpersonal and bimodal concepts.

PMID- 8527360
TI  - Miscarriage experience and the role of support systems: a pilot study.
AB  - A pilot study was carried out with 24 women with the main aim of examining
      retrospectively the experience of miscarriage to indicate issues worthy of
      further investigation. It was found that the psychological sequelae following
      miscarriage appear to be similar to the bereavement process. Whilst social
      support from partners, relatives and friends was helpful, subjects did not
      perceive that support from professionals and the wider community was always
      adequate.

PMID- 8527361
TI  - Musical responsiveness and blocked capacity for intimacy: a comparison of music
      and psychology students.
AB  - The hypothesis that music serves a compensatory emotional need, specifically that
      blocked capacity for intimacy would predict musical responsiveness, was examined
      in musicians and psychologists. Music and psychology students completed a musical
      preference scale and measures of personal relationships and capacity for
      intimacy. Degree of musical responsiveness was significantly related to a blocked
      capacity for intimacy in music students but these measures were non-significantly
      negatively related in psychology students. For the latter group, musical
      preference (i.e. degree of liking for different kinds of music) and measures of
      blocked capacity for intimacy were significantly negatively related to reported
      time spent listening to music. The results for music students are consistent with
      the Freudian hypothesis of sublimation and extend the work of Machotka in the
      realm of visual arts to that of music. The results for psychology students,
      however, indicate that for them music is not serving an aesthetic function in the
      sense defined by Wallach (1959). The most plausible explanation for the
      difference between music and psychology students is in terms of anxiety as a
      mediating variable.

PMID- 8527362
TI  - Severity of ganglion cell death during early postnatal development is modulated
      by both neuronal activity and binocular competition.
AB  - The influence of postnatal neuronal activity on the magnitude of retinal ganglion
      cell death has been studied in cats. A constant blockade of activity in one eye
      starting just after birth does not change the severity of naturally occurring
      ganglion cell death, and as in normal animals, the ganglion cell population
      declines from 250,000 to 160,000 over a 4- to 6-week period. However, the
      population of retinal ganglion cells in the active untreated eye of monocularly
      deprived cats is increased 12% above normal (180,000 vs. 160,000 in each of four
      cases). This increase of 20,000 cells is permanent, and presumably reflects the
      competitive advantage in their target nuclei that the still active axons have
      over their silenced companions from the treated eye. Surprisingly, in one animal
      treated successfully for long duration with TTX in both from the population of
      ganglion cells was elevated in both eyes (200,000 and 208,000 ganglion cells).
      This increase matches that achieved by early unilateral enucleation (Williams et
      al., 1983). Our results demonstrate that the complete blockade of activity
      reduces the severity of naturally occurring cell death in a population of CNS
      sensory neurons. The effects of unilateral blockade emphasize that the activity
      dependent modulation of neuron death only occurs under conditions that do not
      place the inactive population of neurons at a competitive disadvantage.

PMID- 8527363
TI  - Dark-suppression and light-sensitization of horizontal cell responses in the
      hybrid bass retina.
AB  - The responsiveness of luminosity-type horizontal cells, recorded intracellularly
      from isolated hybrid bass retinas, decreased after superfusion for 2 h in
      constant darkness. Responsiveness was subsequently increased (light-sensitized)
      up to 10-fold after exposure to several short (approximately 0.5 min) periods of
      continuous illumination. The increase in horizontal cell responsiveness following
      light-sensitization was due to an increase of peak response amplitude rather than
      a reduction of peak response time. The increased responsiveness after light
      sensitization was intensity-dependent with brighter sensitizing stimuli causing a
      greater increase than dimmer stimuli. The extent of LHC dark-suppression was
      affected by the time of day, being greater when induced during the night than
      during the day. However, there was no significant difference in horizontal cell
      responsiveness after light-sensitization in retinas studied during the night
      compared to those studied during the day. The responsiveness of light-sensitized
      horizontal cells from isolated hybrid bass retinas was found to be suppressed by
      relatively brief periods of darkness. The responsiveness of horizontal cells,
      that were first light-sensitized, decreased by more than 50% following only 5 min
      of darkness. Suppression of light-sensitized horizontal cell responsiveness after
      such a short time in the dark has not been described in other teleost retinas.
      The suppression of light-sensitized horizontal cell responsiveness in hybrid bass
      retinas may be rapid in comparison to other teleosts.

PMID- 8527364
TI  - Dynamics of the orientation tuning of postsynaptic potentials in the cat visual
      cortex.
AB  - We evaluated the dynamic aspects of the orientation tuning of the input to cat
      visual cortical neurons by analyzing the postsynaptic potentials (PSPs) evoked by
      flashing bars of light. The PSPs were recorded using in vivo whole-cell
      technique, and we analyzed the orientation tuning during subsequent temporal
      windows after stimulus onset and offset. Our results show that the amplitudes of
      the postsynaptic potential are reliably tuned to orientation and matching that of
      the spike responses only during certain temporal windows. During the first 100 ms
      after stimulus presentation, orientation tuning of the membrane potential
      underwent regular changes. Within particular intervals, orientation tuning of the
      input was much sharper than that estimated according to the whole response. In
      most cells, optimal orientation was usually stable over the whole period. In
      several cells which had a second hump of EPSPs in the response, this second hump
      was tuned to the same orientation as the first one, but always showed sharper
      tuning. Estimation of the integration time revealed sufficient delay between the
      appearance of EPSPs and spikes, to let inhibition influence spike generation.
      These results show that orientation selectivity of the input to cortical cells is
      a dynamic function, and also indicate the possibility of temporal coding in the
      visual system.

PMID- 8527365
TI  - Activity correlates of cytochrome oxidase-defined compartments in granular and
      supragranular layers of primary visual cortex of the macaque monkey.
AB  - To determine if changes in metabolic capacity revealed by cytochrome oxidase (CO)
      histochemistry are related to sustained changes in energy-utilizing neuronal
      activity, we assayed CO levels and recorded multiunit firing rates along nearly
      tangential penetrations of V1 in seven adult macaque monkeys before and after
      single, monocular injections of TTX. Within as little as 14 h, TTX blockade began
      to reduce CO staining in zones of layer 4C that received dominant input from the
      injected eye. Since simple monocular occlusion has only minor effects on cortical
      CO levels (Trusk et al., 1990), the changes in activity that were specifically
      associated with CO depletion were isolated by comparing spike rates during
      monocular TTX blockade and during monocular occlusion. Five second samples of
      multiunit spike rate were obtained after 2-min adaptation to each of four
      adapting fields: black, gray, white, and textured. Results were similar for these
      four conditions. In layer 4C, ocular dominance zones with input from the TTX eye
      had ongoing spike rates that were 48% of the rates in zones with input from a
      normal but occluded eye. In six animals, it was possible to record activity at a
      single site before, during, and after the onset of TTX blockade. Background
      activity at these interpuff sites decreased as much as 3-fold in less than 1 h
      but stabilized within 3-4 h to an average of 53% of pre-TTX rates. These data
      support the interpretation that energy utilization linked to sustained spike
      rates partially regulates CO levels under normal conditions, at least in layer 4.
      Furthermore, changes in neuronal activity induced by retinal TTX preceded the
      detectable reduction in CO activity in V1 suggesting that the adjustment of CO
      levels was in response to the altered activity.

PMID- 8527366
TI  - Functional role of GABA in cat retina: I. Effects of GABAA agonists.
AB  - Putative GABAergic mechanisms were studied in perfused cat retina by means of
      intracellular recording and application of GABA and the GABAA agonists delta
      amino valeric acid (dAVA), muscimol, and THIP. In contrast to results reported
      previously for cold-blooded vertebrates, introduction of 20 mM GABA into the
      superfusate had no influence upon the response properties of cat retinal
      horizontal cells (HCs). In common with results reported in cold-blooded
      vertebrates, introduction of the GABAA agonists dAVA (2-12 mM) and THIP or
      muscimol (0.2-1 mM) had four consistent reversible influences upon the response
      properties of cat retinal HCs: (1) they reduced photic-response amplitude, (2)
      slowed response onset, (3) slowed response offset, and (4) depolarized the dark
      membrane potential. Both rod and cone signal components were affected. GABAA
      agonists had similar influences upon both the time course and amplitude of
      responses recorded from amacrine and ganglion cells. In all cell types examined,
      the influence upon response kinetics was made particularly apparent with rapidly
      flickering stimuli. Flicker responses were reduced in amplitude much more than
      sustained responses. These results suggest that, in addition to other influences,
      GABAergic action serves to modify the time course of photic responses in both the
      inner and outer plexiform layer of mammalian retina making responses slower and
      less phasic.

PMID- 8527367
TI  - Functional role of GABA in cat retina: II. Effects of GABAA antagonists.
AB  - Putative GABAergic mechanisms were studied in the cat retina by exogenous
      application of the GABAA antagonists picrotoxin (PTX), native bicuculline (BCC),
      and bicuculline methyl bromide (BCC MeBr). When recording intracellular responses
      from horizontal cells (HCs) and amacrine cells as well as electroretinograms
      (ERGs), drugs were added to the perfusate used to maintain the isolated eyecup;
      when recording extracellular spikes from ganglion cells of anesthetized cats,
      drugs were introduced by iontophoretic injection. Both PTX and BCC MeBr had
      relatively little influence upon the response properties of HCs. In contrast,
      native BCC tended to decrease the amplitude of and to slow the photic response to
      light onset and both to quicken and to increase the amplitude of response to
      light offset; in the presence of native BCC, HC responses were dominated by a
      prominent spike-like "Off-overshoot." The influence of GABAA agonists upon HC
      responses was not blocked by GABAA antagonists. ERG b-wave amplitude was reduced
      both by PTX and by native BCC, but was not influenced by BCC MeBr. Latency (time
      to half-peak) was increased by low doses of native BCC, and to a lesser extent
      PTX but not BCC MeBr. Rod-amacrine On-transient responses were increased in
      amplitude by PTX. Extracellular recordings from On- and Off- X and Y ganglion
      cell types became considerably more transient with application of either PTX,
      native BCC, or BCC MeBr; this tendency was greater in Off-type ganglion cells.
      Collectively, these results strengthen conclusions from the previous paper
      suggesting that GABA serves to slow onset and offset kinetics of retinal neurons,
      making them more sustained and less phasic. They also suggest that in mammalian
      retina heterogeneous types of GABAA receptors exist, segregated into different
      zones: a distal zone, sensitive only to native BCC, a central zone sensitive to
      both native BCC and PTX, and a proximal zone sensitive to native BCC, BCC methyl
      halides (BCC MeH), and PTX. Only the proximal zone obeys conventional GABAA
      pharmacology.

PMID- 8527368
TI  - Tryptophan hydroxylase is expressed by photoreceptors in Xenopus laevis retina.
AB  - Serotonin has important roles, both as a neurotransmitter and as a precursor for
      melatonin synthesis. In the vertebrate retina, the role and the localization of
      serotonin have been controversial. Studies examining serotonin immunoreactivity
      and uptake of radiolabeled serotonin have localized serotonin to inner retinal
      neurons, particularly populations of amacrine cells, and have proposed that these
      cells are the sites of serotonin synthesis. However, other reports identify other
      cells, such as bipolars and photoreceptors, as serotonergic neurons. Tryptophan
      hydroxylase (TPH), the rate-limiting enzyme in the serotonin synthetic pathway,
      was recently cloned from Xenopus laevis retina, providing a specific probe for
      localization of serotonin synthesis. Here we demonstrate that the majority of
      retinal mRNA encoding TPH is present in photoreceptor cells in Xenopus laevis
      retina. These cells also contain TPH enzyme activity. Therefore, in addition to
      being the site of melatonin synthesis, the photoreceptor cells also synthesize
      serotonin, providing a supply of the substrate needed for the production of
      melatonin.

PMID- 8527369
TI  - Retinotopic organization of the superior colliculus in relation to the retinal
      distribution of afferent ganglion cells.
AB  - Sensory representations in the brain exhibit topographic variations in
      magnification. These variations have been thought to reflect regional differences
      in the density of innervation at the sensory receptor surface. In the primate
      visual cortex, for example, local magnification factors have been reported to be
      proportional to the corresponding densities of retinal ganglion cells. We sought
      to learn whether this principle also operates in a second major retinofugal
      pathway--the projection to the superior colliculus. In cats, we first used
      retrograde transport to determine the retinal distributions of the ganglion cells
      that project to the colliculus. Then, we compared the numbers of colliculopetal
      ganglion cells in selected retinal sectors to the areas of the corresponding
      collicular representations. Collicular areal magnification was not simply
      proportional to the density of afferent ganglion cells, being instead at least 5
      fold greater than expected in the representation of the central visual field.
      These data imply that incoming retinal afferents are more widely spaced in the
      central regions of the tectal map than in the map's periphery. Such variations in
      afferent density appear to play as large a role as the distribution of ganglion
      cells in determining the metric of the collicular map.

PMID- 8527370
TI  - On the distribution of gamma cells in the cat retina.
AB  - Ganglion cells of the cat retina that are neither alpha nor beta cells are often
      lumped for convenience into a single anatomical group--the gamma cells (Boycott &
      Wassle, 1974; Stone, 1983; Wassle & Boycott, 1991). Defined in this way, gamma
      cells are the morphological counterpart to the physiological W-cell class, which
      includes all ganglion cells that are neither Y (alpha) nor X (beta) cells. We
      have estimated the retinal distribution of gamma cells by using retrograde
      transport to label ganglion cells innervating the superior colliculus and by
      assuming that these included virtually all gamma cells and no beta cells. We
      excluded labeled alpha cells on the basis of soma size. Our data suggest that
      gamma cells represent just under half of the ganglion cells in most of the nasal
      retina, but only about a third of those in the area centralis and temporal
      retina. Gamma cells do not appear to be more highly concentrated in the nasal
      visual streak than are other ganglion cells. In the temporal retina, gamma cells
      with crossed projections to the brain are apparently at least twice as common as
      those with uncrossed projections.

PMID- 8527371
TI  - Qualitative and quantitative features of axons projecting from caudal to rostral
      inferior temporal cortex of squirrel monkeys.
AB  - On the basis of cortical and subcortical connections and architectonics, inferior
      temporal (IT) cortex of squirrel monkeys consists of a caudal region, ITC, with
      dorsal (ITCd) and ventral (ITCv) subdivisions; a rostral region, ITR; and
      possibly a third region intermediate to ITC and ITR, ITI (Weller & Steele, 1992;
      Steele & Weller, 1993). The present study qualitatively and quantitatively
      examined the terminal arborizations of 26 axons in ITR and ITI labeled by
      injections of biocytin or, in one case, horseradish peroxidase, in ITCv. The
      majority of axons gave rise to a single terminal arbor, with a small number
      branching into two overlapping or nearby arbors. Presumptive terminal
      specializations consisted of rounded, bead-like swellings, most often located en
      passant. All axons terminated in layer 4 of cortex, and most had additional
      terminations in layers 3 and 5. The total extent of each axon's terminal arbor
      was 125-750 microns dorsoventrally (mean = 360.6 microns) and 150-725 microns
      anteroposteriorly (mean = 328.1 microns; all values uncorrected for shrinkage).
      In most axons, especially those with larger terminal fields, boutons were not
      uniformly distributed, but formed 2-4 clumps (mean = 2.2), with a mean width of
      149 microns, separated by narrower regions of fewer boutons. Based on a cluster
      analysis of characteristics of the 26 axons, axons projecting from caudal (ITCv)
      to rostral (ITR or ITI) IT cortex of squirrel monkeys comprised three groups that
      we called Type I, Type II, and Type III. Type I axons, the smallest in area
      extent of terminal arbor, terminated predominantly in dorsal ITR. Type III axons,
      largest in areal extent, and Type II axons, intermediate in areal extent,
      terminated in ventral ITR and throughout ITI. The three classes of axons may
      correspond to different types of visual information entering rostral IT cortex.
      The clumping of boutons suggests that individual axons terminate in limited
      patches within their terminal fields.

PMID- 8527372
TI  - Receiver operating characteristic (ROC) analysis of neurons in the cat's lateral
      geniculate nucleus during tonic and burst response mode.
AB  - Relay cells of the lateral geniculate nucleus respond to visual stimuli in one of
      two modes: burst and tonic. The burst mode depends on the activation of a voltage
      dependent, Ca2+ conductance underlying the low threshold spike. This conductance
      is inactivated at depolarized membrane potentials, but when activated from
      hyperpolarized levels, it leads to a large, triangular, nearly all-or-none
      depolarization. Typically, riding its crest is a high-frequency barrage of action
      potentials. Low threshold spikes thus provide a nonlinear amplification allowing
      hyperpolarized relay neurons to respond to depolarizing inputs, including retinal
      EPSPs. In contrast, the tonic mode is characterized by a steady stream of unitary
      action potentials that more linearly reflects the visual stimulus. In this study,
      we tested possible differences in detection between response modes of 103
      geniculate neurons by constructing receiver operating characteristic (ROC) curves
      for responses to visual stimuli (drifting sine-wave gratings and flashing spots).
      Detectability was determined from the ROC curves by computing the area under each
      curve, known as the ROC area. Most cells switched between modes during recording,
      evidently due to small shifts in membrane potential that affected the activation
      state of the low threshold spike. We found that the more often a cell responded
      in burst mode, the larger its ROC area. This was true for responses to optimal
      and nonoptimal visual stimuli, the latter including nonoptimal spatial
      frequencies and low stimulus contrasts. The larger ROC areas associated with
      burst mode were due to a reduced spontaneous activity and roughly equivalent
      level of visually evoked response when compared to tonic mode. We performed a
      within-cell analysis on a subset of 22 cells that switched modes during
      recording. Every cell, whether tested with a low contrast or high contrast visual
      stimulus exhibited a larger ROC area during its burst response mode than during
      its tonic mode. We conclude that burst responses better support signal detection
      than do tonic responses. Thus, burst responses, while less linear and perhaps
      less useful in providing a detailed analysis of visual stimuli, improve target
      detection. The tonic mode, with its more linear response, seems better suited for
      signal analysis rather than signal detection.

PMID- 8527373
TI  - Sensitivity to full-field visual movement compatible with head rotation:
      variations among axes of rotation.
AB  - Movement detection thresholds for full-field visual motion about various axes
      were measured in three subjects using a two-alternative forced-choice staircase
      method. Thresholds for 1-s exposures to rotation about different rotation axes
      varied significantly over the range 0.139 +/- 0.05 deg/s to 0.463 +/- 0.166
      deg/s. The highest thresholds were found in response to rotation about axes
      closely aligned to the line of sight. Variations among the thresholds for
      different axes could not be explained by different movement patterns in the fovea
      or variations in motion sensitivity with eccentricity. The variations can be well
      simulated by a three-channel model for coding the axis and velocity of full-field
      visual motion. A three-channel visual coding system would be well suited for
      extracting information about self-rotation from a complex pattern of retinal
      image motion containing components due to both rotation and translation. A three
      channel visual motion system would also be readily compatible with vestibular
      information concerning self-rotation arising from the semicircular canals.

PMID- 8527374
TI  - Functional properties of a metabotropic glutamate receptor at dendritic synapses
      of ON bipolar cells in the amphibian retina.
AB  - Perforated patch-voltage and current-clamp recordings were obtained from ON
      bipolar cells in the amphibian retinal slice preparation. The currents produced
      by the photoreceptor transmitter were compared to the currents produced by
      selective metabotropic glutamate agonists: L-2-amino-4-phosphonobutyrate (L-AP4,
      APB) and IS,3R 1-amino-1,3 cyclopentanedicarboxylic acid (1S, 3R ACPD). Both
      agonists produced currents that were very similar to that produced by the
      photoreceptor transmitter in terms of conductance and reversal potential. The
      similarities suggest that the metabotropic glutamate receptors are functionally
      localized to the synaptic region of ON bipolar dendrites. The synaptic
      conductance rarely exceeded the non-synaptic conductance. The mean input
      resistance of ON bipolar neurons was 770 M omega in the light and 1.2 G omega in
      the dark. The average light-regulated synaptic conductance was 57% of the non
      synaptic conductance. The L-AP4 regulated conductance averaged 77% of the non
      synaptic conductance, while the 1S, 3R ACPD regulated conductance averaged 95% of
      the non-synaptic conductance. This balance between synaptic and non-synaptic
      conductance indicates that the synapse will not shunt the cell and the
      conductance ratio serves to maximize incremental gain at the photoreceptor to ON
      bipolar synapse. This conductance mechanism makes the ON bipolar cell well
      equipped to relay rod signals.

PMID- 8527375
TI  - Shifting relationships between photoreceptors and pigment epithelial cells in
      monkey retina: implications for the development of retinal topography.
AB  - This study examines the spatiotemporal relationships between retinal pigment
      epithelium (RPE) and photoreceptors (PR) during development of Macaca nemestrina
      retina. Our aim was to learn more about the developmental dynamics of these two
      important cell populations, particularly whether development changes in RPE cell
      densities mimic those of PR at selected retinal points. Twelve eyes ranging in
      age from 100 fetal days (Fd) to adulthood were flatmounted; the retinal
      perimeters were traced; and then sample punches were taken of the RPE and neural
      retina at the fovea, optic disc, mid- and far-nasal periphery, and far temporal,
      inferior and superior periphery. The two tissues were gently separated and the
      RPE cells and photoreceptors from the same region of the punch were counted using
      Nomarski contrast interference optics. We found that the total number of cones
      remains stable around 4 million between Fd100 and adulthood, but RPE number
      increases from 1.6 million at Fd100 to 2.56 million in adulthood. At the fovea,
      the core:RPE ratio increases from 5.4:1 at Fd100 to 28:1 by adulthood. In the
      temporal periphery by contrast, the cone:RPE ratio declines from 2.2:1 at Fd100
      110 to less than 1:1 in the adult. In the vicinity of the optic disc, the ratio
      of (cones+rods); RPE remains around 35:1 throughout development, but in the
      retinal periphery it decreases to the adult value of 22:1. These changing ratios
      indicate that photoreceptors and RPE cells are redistributed independently during
      development, and that these two cellular sheets slide over one another to achieve
      their final distribution. This situation suggests that the forces or factors
      causing foveation are intrinsic to the neural retina.

PMID- 8527376
TI  - Neonatal administration of the neurotoxin 5,7-dihydroxytryptamine results in
      synaptic reorganization in the superficial gray layer of the hamster's superior
      colliculus.
AB  - Neonatal subcutaneous administration of the neurotoxin 5,7-dihydroxytryptamine
      (5,7-DHT) to hamsters results in a marked depletion of serotonin (5-HT) in cortex
      and an increase in the concentration of this amine in the superior colliculus
      (SC). To determine whether this increase was associated with an alteration in the
      synaptic organization of 5-HT-containing axons in the superficial gray layer of
      the SC, immunocytochemistry was combined with electron microscopy. In normal
      adult hamsters, only 4.0% of 500 5-HT-immunoreactive profiles make synaptic
      contacts in the superficial gray layer of the hamster's SC. In 5,7-DHT-treated
      animals, examination of 400 individual profiles indicated that 25.5% of 5-HT
      positive profiles made synaptic contacts (P < 0.05). Given the recently
      demonstrated effect of 5-HT on retinotectal transmission in this species, the
      present results suggest that the functional organization of the SC may also be
      markedly altered in animals that sustain neonatal 5,7-DHT administration.

PMID- 8527377
TI  - Catecholamine-, indoleamine-, and GABA-containing cells in the chameleon retina.
AB  - Neurons containing catecholamine, indoleamine, and gamma-aminobutyric acid (GABA)
      were identified by immunohistochemistry in the chameleon retina. Tyrosine
      hydroxylase (TH) and serotonin (5HT) were observed mostly in two subtypes of
      orthotopic amacrine cells differing in their soma size and process distribution
      within the IPL. Some labelled cells were displaced either to the IPL (5HT) or the
      GCL (TH and 5HT). A multiplicity of retinal cell types contained GABA including
      cones, horizontal, amacrine, and ganglion cells. Our results confirmed those
      obtained in the retinas of other lizards except for the presence of interstitial
      and displaced amacrine cells containing TH or 5HT of which this is the first
      report.

PMID- 8527378
TI  - Fluorescence in situ hybridization identifies new chromosomal changes involving
      3q27 in non-Hodgkin's lymphomas with BCL6/LAZ3 rearrangement.
AB  - Twelve B-cell non-Hodgkin's lymphomas with BCL6/LAZ3 rearrangement selected from
      a series of 30 lymphomas with cytogenetically detectable 3qter abnormalities were
      characterized at the histological, clinical, and cytogenetic levels, including
      fluorescence in situ hybridization (FISH) analysis, which was performed in all
      cases but one. A classical t(3;14) and t(3;22) were found in three patients
      (25%). In the remaining cases, eleven different 3q27 abnormalities were
      demonstrated and characterized with the use of chromosome painting. Seven of
      twelve "variant" rearrangements identified in our series affecting 1p32, 1p34,
      3p14, 6q23, 12p13, 14q11, and 16p13 have not been reported before. Moreover,
      involvement of both homologs of chromosome 3 in distinct translocations was
      detected as an unexpected result in two cases and was confirmed via FISH in a
      third case. The putative bichromosomal rearrangements of the 3q27 region were
      evidenced by Southern analysis in one of these cases. In another case, FISH with
      a cosmid spanning the 3q27 breakpoint region demonstrated the involvement of
      BCL6/LAZ3 only in one of two t(3q27). In our series, which was selected on
      cytogenetic and molecular criteria, 50% (6 of 12) of cases with BCL6/LAZ3
      rearrangement were diagnosed as diffuse, large B-cell lymphomas (DLCL). Another
      33% (4 of 12) of cases were diagnosed as follicular center lymphomas (FL), with
      t(14;18)/BCL2 rearrangement in all but one case. Furthermore, in three follicular
      lymphoma cases in which multiple samples were analyzed, the disease showed no
      evidence of histological progression during a follow-up period of 3-14
      years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527379
TI  - Comparative genomic hybridization analysis of human sarcomas: II. Identification
      of novel amplicons at 6p and 17p in osteosarcomas.
AB  - Using comparative genomic hybridization (CGH), we have identified and mapped
      regions of DNA amplification in primary and metastatic osteosarcomas. Samples
      were obtained from four patients and ten independent xenografts. Sixty-four
      percent of the tumors showed increased DNA-sequence copy numbers, affecting 23
      different chromosomal sites. Most of these regions were not previously associated
      with the development and/or progression of these tumors. Amplicons originating
      from 1q21-q23, 6p, 8q23-qter, and 17p11-p12 were observed most frequently. The 6p
      and 17p11-p12 amplicons seem to be specific for osteosarcomas, indicating that
      these regions may harbor genes relevant for the development of these tumors.

PMID- 8527380
TI  - Kappa- and lambda-positive cells in centroblastic-centrocytic lymphoma
      (follicular lymphoma) may share a secondary chromosome aberration: reflections on
      early lymphoma development.
AB  - The technique of simultaneous fluorescence immunophenotyping and interphase
      cytogenetics (FICTION) was applied in four cases of centroblastic-centrocytic
      (working formulation: follicular) lymphoma. Our aim in this study was to
      establish whether secondary chromosome aberrations known from a prior cytogenetic
      analysis were detectable in both kappa- and lambda-expressing tumor cells from
      the same lymphoma patient. One of the cases did indeed contain kappa- and lambda
      positive tumor cells with trisomy 8. On the basis of our results, we reflect on
      the events that take place during early development of centroblastic-centrocytic
      lymphoma.

PMID- 8527381
TI  - Identification of two distinct regions of deletion at 6q in gastric carcinoma.
AB  - Loss of heterozygosity (LOH) affecting the long arm of chromosome 6 has been
      found repeatedly in human cancers. Recently, our group reported that del(6)(q21
      22-->qter) was the most consistent structural cytogenetic abnormality in gastric
      carcinomas. To determine more precisely the deleted region, we studied 51 tumors
      with 9 polymorphic markers on this chromosome arm. LOH of one or more markers was
      found in 39% of the tumors. LOH at region 6q22.3 was detected in 50% of
      informative tumors and at 6q26-q27 in 37% of informative tumors. By comparative
      analysis of LOH regions, we identified two separate regions of overlapped
      deletions at 6q, one between 6q16.3-q21 and 6q22.3-q23.1, another distal to 6q23
      q24. A comparison of clinicopathologic features of gastric carcinomas with and
      without LOH at 6q revealed statistically significant or suggestive differences
      between LOH and young age of the patients and proximal location of the tumors.
      The two informative early gastric carcinomas both showed LOH at 6q. The
      occurrence of LOH at 6q was similar in all histological types. We conclude that
      two distinct regions at 6q appear to be involved in the early stages of gastric
      carcinogenesis.

PMID- 8527382
TI  - Balanced translocation in a neuroblastoma patient disrupts a cluster of small
      nuclear RNA U1 and tRNA genes in chromosomal band 1p36.
AB  - Chromosomal band 1p36 probably harbours several neuroblastoma suppressor genes. A
      neuroblastoma patient has been described with a constitutional balanced
      translocation, t(1;17)(p36;q12-21). Cytogenetically, no loss of chromosomal
      material was visible. The 1p36 translocation breakpoint could therefore have
      inactivated one allele of a tumour suppressor gene, thus predisposing the patient
      to develop neuroblastoma. We localized this breakpoint by pulsed field gel
      electrophoresis, analysis of yeast artificial chromosomes, and fluorescence in
      situ hybridization. Here we report that the breakpoint is within a large cluster
      of small nuclear RNA U1 (RNU1) and some tRNA genes (TRE, TRN) on chromosomal band
      1p36. The size of this cluster is over two megabases and it contains many other
      locally repeated sequences. Polyadenylated transcripts were identified for some
      of these sequences. In addition, the cluster is the target for integration of an
      adenovirus 5/SV40 hybrid virus. The translocation breakpoint maps distal of this
      viral integration site and proximal of marker PND.

PMID- 8527383
TI  - Distinct Xp11.2 breakpoints in two renal cell carcinomas exhibiting X;autosome
      translocations.
AB  - Several human renal cell carcinomas with X;autosome translocations have been
      reported in recent years. The t(X;1)(p11.2;q21) appears to be a specific primary
      anomaly, suggesting that tumors with this translocation form a distinct subgroup
      of RCC. Here we report two new cases, one with a t(X;10)(p11.2;q23), the other
      with a t(X;1)(p11.2;p34). The common breakpoint in Xp11.2 suggests that they
      belong to the above-mentioned subset of RCC. Using FISH in conjunction with X
      specific YAC clones, we demonstrate that the two new cases exhibited distinct
      breakpoints within Xp11.2.

PMID- 8527384
TI  - Molecular and cytogenetic analysis of chromosome 7 in uterine leiomyomas.
AB  - Uterine leiomyomas are benign tumors that arise clonally from smooth muscle cells
      of the myometrium. Cytogenetic studies of uterine leiomyomas have shown that
      about 40% have chromosome abnormalities and that deletion of 7q is a common
      finding. The observations suggest the possible location of a growth-suppressor
      gene within the 7q21-q22 region. Molecular genetic analysis of cytogenetically
      normal tumors has frequently shown somatic loss of specific tumor suppressor
      genes detected by loss of heterozygosity in the critical region. To test the
      hypothesis that chromosome region 7q21-q22 contains a growth-suppressor gene
      involved in the development of leiomyomas, we examined 92 leiomyomas for allelic
      loss of 7q markers spanning the cytogenetically defined critical region. Forty
      tumors with cytogenetically defined 7q deletion, 45 tumors without
      cytogenetically visible 7q deletion, and seven tumors with no cytogenetic
      information were examined for allelic loss of loci D7S489, D7S440, D7S492,
      D7S518, D7S471, D7S466, and D7S530. Loss of heterozygosity for one or more of
      these loci was observed in 23 of 40 (57.5%) of the tumors with deletion of 7q and
      in 2 of 45 cases without a cytogenetically visible deletion. The tumors with
      cytogenetic deletion of 7q, but no loss of 7q21-q22 markers, were mosaics, with
      only a minority of cells containing the cytogenetic deletion. The critical region
      of loss is defined by the markers D7S518 and D7S471, each showing loss in
      approximately 50% of informative cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527385
TI  - Fluorescence in situ hybridization analysis of whole-arm 7;12 translocations in
      hematologic malignancies.
AB  - Cytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute
      lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts
      (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12
      translocations mapped the breakpoints to the centromeres on both chromosomes. The
      rearrangements were interpreted as the whole-arm translocations
      der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and
      AMLL. However, further analysis by metaphase and/or interphase fluorescence in
      situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the
      RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present
      in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all
      four cases, the corresponding chromosome 7 imbalances differed--monosomy for 7q
      in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic
      neoplasms with unbalanced whole-arm or near-centromeric 7;12 translocations and
      seven dic(7;12) with juxtacentromeric breakpoints have been reported previously:
      2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases
      had loss of 12p material. All but one of the cases with combined 7p and 12p
      deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid
      differentiation. No particular clinical, morphologic, or immunophenotypic
      features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12),
      often together with 5q deletions, might be associated with previous genotoxic
      exposure and poor prognosis.

PMID- 8527386
TI  - Mitochondrial ATP synthase alpha-subunit gene amplified in a retinoblastoma cell
      line maps to chromosome 18.
AB  - The human retinoblastoma cell line Y79 has multiple copies of the MYCN gene and
      the DEAD box gene DDXI. Both genes have been mapped to chromosome band 2p24. A
      third gene, encoding the alpha-subunit of mitochondrial ATP synthase (ATPSA), is
      also amplified in Y79. Here we report that there are at least four human
      mitochondrial ATPSA-related genes located on four different chromosomes. The
      ATPSA gene that is amplified in Y79 originates from chromosome 18. In Y79, the
      amplified copies of both the ATPSA and the MYCN genes are located on a
      homogeneously staining region (HSR) at chromosome band Ip34.

PMID- 8527387
TI  - Regional fine mapping of the multiple-aberration region involved in uterine
      leiomyoma, lipoma, and pleomorphic adenoma of the salivary gland to 12q15.
AB  - Cytogenetic aberrations involving 12q13-15 are frequently observed in a variety
      of benign solid tumors. Using a chromosome walking approach combined with
      fluorescence in situ hybridization analysis, we were able to show that the
      chromosome 12 breakpoints involved in uterine leiomyoma, pleomorphic adenoma of
      the salivary gland, and lipoma cluster to the same chromosomal region, which we
      therefore designated MAR (multiple-aberration region). By comparing the G-banding
      pattern of prometaphase chromosomes of amniotic fluid cells and lymphocytes to
      the position of hybridization signals obtained with a cosmid pool encompassing
      this breakpoint hot spot region, MAR was assigned to 12q15. We conclude that,
      despite the cytogenetic breakpoint assignment to the three bands 12q13-15 in
      individual uterine leiomyomas, lipomas, and pleomorphic adenomas of the salivary
      glands in the past, most likely 12q15 is the only 12q breakpoint site in these
      three distinct solid tumor types.

PMID- 8527388
TI  - TP53 mutations and breast cancer prognosis: particularly poor survival rates for
      cases with mutations in the zinc-binding domains.
AB  - Acquired mutations in TP53 as well as immunohistochemically detectable protein
      expression have been implicated as prognostic factors for breast cancer. We have
      evaluated the relationship between mutations detected in 119 breast tumours and
      various clinicohistopathological indices, stratifying the mutations according to
      the functional domains as defined by the recent elucidation of the crystal
      structure of the protein. Patients with missense mutations located in regions
      encoding parts of the protein involved in zinc-binding had significantly
      decreased disease-free and overall survival relative to patients whose tumours
      had mutations in other domains. These results indicate that these biochemically
      defined domains also have biological relevance in terms of breast cancer disease
      course, and suggest that some mutations in TP53, more than others, can contribute
      to the development of clinically more aggressive and perhaps treatment resistant
      breast tumours. When confirmed, this will be of potential importance in
      predicting the clinical behaviour of breast cancer and its responsiveness to
      therapy.

PMID- 8527389
TI  - Complex MLL rearrangement in a patient with T-cell acute lymphoblastic leukemia.
AB  - MLL (also known as ALL-I, HTRX, or HRX) gene translocations are among the most
      common chromosomal abnormalities recognized in both B-lineage acute lymphoblastic
      leukemia (ALL) and acute myeloid leukemia (AML). However, MLL gene rearrangements
      are uncommon in T-cell ALL. We recently detected an MLL gene rearrangement in a
      patient with typical T-cell ALL. We recently detected an MLL gene rearrangement
      in a patient with typical T-cell ALL (CD2+, CD4+, CD5+, CD7+, CD8+, HLA DR-) and
      an apparently normal karyotype (46,XX). The rearrangement was cloned and
      characterized; a DNA fragment distal to the breakpoint was mapped by fluorescence
      in situ hybridization (FISH) to 19p13, indicating that the leukemic blasts had
      undergone a cytogenetically undetected rearrangement involving chromosomes 11 and
      19. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated
      an in-frame fusion mRNA between the amino terminus of MLL and the carboxy
      terminus of ENL (also known as MLLT1 or LTG19), a gene that has been mapped to
      19p13. In addition, MLL sequences distal (telomeric) to the breakpoint were
      deleted from the genome, which precludes the formation of a reciprocal ENL/MLL
      fusion protein. These findings suggest that an MLL/ENL fusion protein (and not a
      reciprocal ENL/MLL fusion) was likely to be pathogenic in this patient, and they
      reinforce previous studies showing that leukemic blasts with apparently normal
      karyotype may harbor MLL rearrangements. Additionally, this report provides the
      first conclusive evidence of an MLL/ENL gene fusion characterized at a molecular
      level in a patient with T-cell ALL.

PMID- 8527390
TI  - Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of
      genomic imbalances and identification of a novel major amplicon at 1q21-q22 in
      soft tissue sarcomas.
AB  - Comparative genomic hybridization (CGH) was recently developed as a tool to
      survey entire genomes for variations in DNA sequence copy numbers. We have
      applied this technique to detect and map amplified regions in 54 soft tissue
      sarcomas. Aberrations were detected by visual analysis of hybridizations or
      contrast-enhanced digital images, followed by quantitative digital ratio imaging
      of the aberrant chromosomes. Several tumors showed increased DNA sequence copy
      number at 12q14, as expected. However, CGH analysis detected amplification of
      12q14 also in some tumors where neither MDM2 nor CDK4 was amplified, suggesting
      that another as yet unknown gene(s) may drive amplification of this region in
      sarcomas. Furthermore, a novel recurring amplicon was detected at 1q21-q22. DNA
      amplifications coinciding with this segment were as frequent as those observed
      for 12q14, indicating that 1q21-q22-linked gene(s) may also play an important
      role in the development and/or progression of human soft tissue sarcomas.

PMID- 8527391
TI  - Genetic analysis of chromosome 13 deletions in BCR/ABL negative chronic
      myeloproliferative disorders.
AB  - Chromosomal deletions of band 13q14 occur recurrently in BCR/ABL negative chronic
      myeloproliferative disorders (CMPD), including myelosclerosis with myeloid
      metaplasia (MMM), polycythemia vera (PV), essential thrombocythemia (ET),
      juvenile chronic myeloid leukemia (JCML), and the so-called BCR/ABL- chronic
      myeloid leukemia (CML). The RBI tumor suppressor locus, mapping to 13q14, has
      long since been hypothesized as the important gene. In this report, we have
      determined the frequency of 13q14 deletions at the molecular level in a large
      panel of BCR/ABL- CMPD at different disease stages and performed a detailed
      genetic analysis of gross rearrangements/deletions and point mutations of the RBI
      gene in these disorders. Our data show that molecular deletions of 13q14 are
      detected in a relatively large fraction of BCR/ABL- CMPD (38%), that they appear
      to be more frequent in MMM than in other BCR/ABL- CMPD, and that they may be
      present at diagnosis or occur during blastic evolution of the neoplasia. The RBI
      gene displayed a germline configuration in all BCR/ABL- CMPD tested, suggesting
      that 13q14 deletions in these disorders affect a tumor suppressor locus distinct
      from RBI.

PMID- 8527392
TI  - Localization of metastasis suppressor gene(s) for rat prostatic cancer to the
      long arm of human chromosome 10.
AB  - To examine the role of human chromosome 10 in development of prostatic cancer, we
      introduced human chromosome 10 into highly metastatic rat prostatic cancer cells
      by microcell-mediated chromosome transfer. Microcell hybrid cells introduced with
      human chromosome 10 showed suppression of the metastatic ability to the lung to
      some extent without any suppression of tumorigenicity, although the tumor growth
      rate decreased slightly. To minimize the region that contains metastasis
      suppressive activity, the hybrid cells in metastasis foci of lung were
      established in culture and reanalyzed for portions of human chromosome 10
      retained in the metastasis tissues. Cytogenetic and molecular analyses
      demonstrated that loss of the region between 10cen and D10S215 on human
      chromosome arm 10q was related to expression of the metastatic phenotype. These
      results demonstrate that the region between 10cen and D10S215 on human chromosome
      arm 10q contains at least one of the metastasis suppressor genes for rat
      prostatic cancer.

PMID- 8527393
TI  - Normal human chromosome 2 induces cellular senescence in the human cervical
      carcinoma cell line SiHa.
AB  - For identification of the chromosome carrying cellular senescence-inducing
      activity, normal human chromosome 2, 3, 6, 7, 9, 11, or 12 tagged with a
      selectable marker gene (neo) was introduced into the human cervical carcinoma
      cell line SiHa via microcell-mediated chromosome transfer. Seventy-six percent
      (158/207) of the G418-resistant clones obtained by the transfer of chromosome 2
      showed a remarkable change in morphology (cells were flat), and 93% (147/158) of
      them ceased to divide (senesced) prior to 6-9 population doublings, whereas most
      of the clones generated by the transfer of other chromosomes exhibited a
      morphology similar to that of the parental cells and continued to grow.
      Chromosome analyses suggested that cells which escaped from senescence contained
      only a small fragment derived from the transferred chromosome 2, whereas the
      transferred chromosomes were apparently intact in most of the continuously
      growing microcell hybrids with introduction of other chromosomes. These results
      indicate that the normal human chromosome 2 carries a gene or genes that induce
      cellular senescence in SiHa cells.

PMID- 8527394
TI  - Microsatellite instability in endometrial carcinomas: frequent replication errors
      in tumors of early onset and/or of poorly differentiated type.
AB  - Endometrial and ovarian carcinomas are common among women belonging to hereditary
      nonpolyposis colorectal carcinoma (HNPCC) families; tumors developing in them are
      characterized by genetic instability due to an inherited dysfunction of the DNA
      mismatch-repair system. To clarify the role of similar genetic factors in
      sporadic forms of gynecological tumors, we examined 77 endometrial and 68 ovarian
      carcinomas for replication error (RER) at five microsatellite loci. RER-positive
      phenotypes at two or more microsatellite loci were observed in 18 of the
      endometrial carcinomas, but in only two of the ovarian carcinomas. Among the
      patients with endometrial carcinomas, the frequency of RER tended to be higher in
      those under age 50 than in those over age 60. Furthermore, RER was significantly
      more frequent in poorly differentiated than in well-differentiated tumors (P =
      0.008, Fisher's exact test). These data suggest that genetic factors
      characterized by RER are likely to play an important role in some endometrial
      carcinomas, particularly those of early onset and/or of the poorly differentiated
      type.

PMID- 8527395
TI  - No recurrent structural abnormalities apart from i(12p) in primary germ cell
      tumors of the adult testis.
AB  - Malignant transformation may be caused by gene deregulation resulting from
      specific chromosomal rearrangements, by amplification, by mutations in proto
      oncogenes, by loss of tumor suppressor genes, or a combination of these. We
      investigated the role of numerical and structural chromosomal abnormalities in
      102 cytogenetically abnormal cases of primary testicular germ cell tumors of
      adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell
      tumors (NS)]. We confirmed that an isochromosome for 12p, i(12p), is the only
      consistent structural chromosomal abnormality in TGCT, present in about 70% of
      our cases. Both the frequency and the number of copies of i(12p) are higher in NS
      than in SE. This may suggest that i(12p) is involved in tumor progression.
      Besides i(12p), several clonal structural chromosomal abnormalities were found,
      but none appeared to be specific. SE and NS had chromosome numbers in the
      triploid range, with significantly higher numbers in SE than in NS (average modal
      chromosome numbers of 73.4 in SE and 65.0 in NS). Both in SE and NS, some
      chromosomes were significantly underrepresented (e.g., 11, 13, 18, and Y) and
      others overrepresented (e.g., 7, 8, 12, 21, and X). In SE, a significantly higher
      copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower
      number of chromosome 17, compared with NS. These chromosomes may play an
      important role in the differentiation of TGCT.

PMID- 8527396
TI  - Allelic loss in squamous cell carcinomas of the larynx: discordance between
      primary and metastatic tumors.
AB  - The mutational inactivation of suppressor genes, a process required for cancer
      progression, generates new genetic subclones within a tumor. The allelic losses
      that frequently unmask these mutations serve not only as markers of the
      chromosomal locations of these genes but also as clonal fingerprints of the
      shifting relationships between these genetically heterogeneous cell populations.
      The rise of the metastasis-competent subclone to dominance within the primary
      tumor should be reflected in the similarity of the genetic fingerprints of the
      primary tumor and its resultant metastases. We have tested this hypothesis by
      comparing the patterns of allelic loss of individual primary laryngeal squamous
      cell carcinomas and their resultant cervical lymph node metastases at 16
      different genetically polymorphic loci on 15 chromosome arms. Although primary
      tumors and metastases both frequently lose heterozygosity on the same chromosome
      arms (3p, 9p, 9q, 13q, and 17p), five of the 12 metastases differed from their
      primary tumors at one or two of the loci examined. Discordance between the two
      tumor cell populations from the same patient is suggestive of either subclone
      heterogeneity within the primary tumor at the time of establishment of the
      metastasis or further clonal evolution of both tumors after metastasis.

PMID- 8527397
TI  - Chromosomes in gliomatosis cerebri.
AB  - Gliomatosis cerebri is a rare brain tumor which histologically resembles a
      diffuse cerebral astrocytoma. It can simultaneously infiltrate multiple sites in
      the cerebrum, cerebellum, brainstem, and spinal cord. This remarkable diffuseness
      has led to the idea that gliomatosis cerebri does not derive from a solitary
      focus but must arise from a broad field of glial cells. We studied the
      chromosomes from gliomatosis cerebri in a 12-year-old boy by conventional
      cytogenetics and fluorescence in situ hybridization (FISH). Aside from normal
      cells, we found a majority of cells with the karyotype
      44,XY,del(6)(q25),del(14)(q21),
      der(15;21)(q10;q10),add(18)(q22),del(19)(p12),add(20)(p13),-21. A smaller
      proportion of cells had 88 chromosomes with a doubling of this abnormal
      karyotype. These findings are consistent with a clonal neoplasm stemming from a
      single cell. The chromosome changes we observed, with the possible exception of
      the chromosome 6 deletion, did not resemble those frequently found in
      astrocytomas. Gliomatosis cerebri may therefore belong to a separate category of
      brain tumors.

PMID- 8527398
TI  - Isochromosome 17q demonstrated by interphase fluorescence in situ hybridization
      in primitive neuroectodermal tumors of the central nervous system.
AB  - We previously reported an i(17q) as a non-random finding in childhood primitive
      neuroectodermal tumors (PNETs) of the central nervous system. In the present
      study, we describe a two-color interphase fluorescence in situ hybridization
      (FISH) assay for detection of chromosome 17 abnormalities in tumors. Thirty-four
      PNETs were analyzed by FISH with a series of chromosome 17-specific probes which
      map to 17p13.3-17q25. The results from the FISH assay were then compared to the
      karyotypes prepared from the tumors. Ten of the 34 cases demonstrated an i(17q)
      by FISH and standard cytogenetics. Two PNETs were shown to have an i(17q) by FISH
      alone, and three additional tumors had deletions of 17p. Thus, a total of 15 of
      34 (44%) of the PNETs in this series had a deletion of 17p. This study confirms
      and extends our previous reports that an i(17q) is the most common cytogenetic
      abnormality in PNETs. The interphase FISH assay which we employed will have
      clinical utility for diagnosis of children with malignant brain tumors, and it
      may be used for identification of tumors with 17p deletions for molecular studies
      aimed at identifying disease genes.

PMID- 8527399
TI  - Genetic instability of chromosome 3 in HPV-immortalized and tumorigenic human
      keratinocytes.
AB  - The HPV-1811 cell line is derived from primary human foreskin keratinocytes that
      have been transfected with human papilloma virus type 18. At late passage, these
      cells produce invasive squamous cell carcinomas when injected into nude mice. A
      striking, but unstable, aberration of chromosome 3 occurs very early after
      establishment of the culture; a consistent rearrangement is observed concomitant
      with tumorigenicity. Using molecular cytogenetic techniques, we characterized the
      complex development of this aberration. A whole chromosome probe to this
      chromosome was made by linker-adapter PCR amplification of a single flow-sorted
      chromosome. Hybridization of this probe to normal metaphase chromosomes revealed
      the der (3) to be composed of chromosome 3, distal 13q, and 21q22. Hybridization
      of a 3q subtelomeric probe and a glycoprotein V probe which maps to 3qter
      indicated that this locus is duplicated in the final form of the chromosome, but
      that much instability occurs prior to its establishment. The ETS2 oncogene, which
      maps to 21q22, is translocated to the der(3) when the cell line becomes
      tumorigenic, but not prior to this time. Early-passage cells which have been
      induced to become tumorigenic by exposure to the carcinogen nitrosomethylurea
      also have the localization of the ETS2 at 3qter.

PMID- 8527400
TI  - Specific decrease of Th1-like activity in mice with plasma cell tumors.
AB  - Previously we examined the ability of the host's immune responses to regulate Ig
      production in an IgE-secreting murine plasma cell tumor (B53). In the present
      study we have examined the reverse phenomenon, in that we have investigated the
      effects of this and other plasma cell tumors on the immune responses of their
      hosts. We found that splenocytes from plasma cell tumor-bearing mice demonstrate
      decreased proliferation in response to polyclonal stimulation by either Con A or
      a combination of PMA and calcium ionophore (A23187). Fractionation of the
      splenocytes demonstrated that this reduction in proliferation was confined to
      CD4+ T cells and that the proliferation of CD8+ T cells was unaffected. In order
      to determine whether the down-modulatory effects of the tumor were confined to a
      particular CD4+ helper T cell subset, we examined the production of cytokines
      representing the Th1 subset (IL-2 and IFN-gamma) and the Th2 subset (IL-4 and IL
      10) from stimulated splenocytes and from stimulated enriched splenic T cells. We
      found that both stimulated splenocytes and T cells from plasma cell tumor-bearing
      mice produced lower levels of the Th1 cytokines IL-2 and IFN-gamma compared with
      normal cultures, demonstrating that Th1-like responses are inhibited in the hosts
      of these tumors. However, no alterations in the production of the Th2 cytokines
      IL-4 and IL-10 were observed in these stimulated splenocyte or T cell cultures
      from the tumor-bearing mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527401
TI  - Prevention of endotoxin shock by an antibody against leukocyte integrin beta 2
      through inhibiting production and action of TNF.
AB  - Septic shock remains a serious disorder associated with high mortality.
      Accumulating evidence indicates that TNF is a major and essential mediator of
      endotoxin shock. We report here that administration of an antibody against CD18
      dramatically reduced endotoxin-induced shock in rabbits as revealed by prevention
      of severe hypotension, metabolic acidosis and a pathological change suggestive of
      disseminated intravascular coagulation with concomitant inhibition of elevation
      of plasma TNF activity. The anti-CD18 antibody also inhibited the hypotension
      induced by administering recombinant TNF. Furthermore, an antibody against a
      ligand for CD18 complexes, intercellular adhesion molecule-1, also prevented TNF
      induced shock as well as endotoxin shock in rabbits. These observations suggest
      that adhesion of leukocytes to endothelium may be of primary importance in the
      action of TNF as well as in the production of TNF in vivo and that the antibody
      against adhesion molecules could be of therapeutic benefit in life-threatening
      septic shock in humans.

PMID- 8527402
TI  - Establishment and structural analysis of human mAb to the E2 component of the 2
      oxoglutarate dehydrogenase complex generated from a patient with primary biliary
      cirrhosis.
AB  - We established one Epstein-Barr virus-transformed B cell hybrid clone producing
      human mAb of the IgG class to the 2-oxoglutarate dehydrogenase complex (OGDC) for
      the first time from the peripheral B lymphocytes of a patient with primary
      biliary cirrhosis (PBC). This mAb, designated mAbM37GO37, specifically bound to
      OGDC and its dissociation constant with OGDC was calculated to be 3.70 x 10(-10)
      mol/l. mAbM37GO37 stained murine stomach/kidney cryostat sections in a typical
      immunofluorescence pattern of antimitochondrial antibody (AMA). Western blotting
      analysis revealed that mAbM37GO37 reacted with an E2 component of OGDC but not
      with other components of OGDC nor pyruvate dehydrogenase complex (PDC).
      Furthermore, mAbM37GO37 completely inhibited the enzymatic activity of OGDC. In
      order to determine the structure and genetic origin of anti-OGDC autoantibody, we
      cloned and sequenced the Ig heavy and light chain variable regions of mAbM37GO37.
      This mAb used the VHIII family member, V3-7, and the V kappa IV family member.
      The amino acid difference between the expressed V genes of this mAb and
      respective putative germline genes was concentrated within the complementarity
      determining regions (CDR) rather than the framework regions (FR). The R:S
      mutation ratio was high in the CDR and low in the FR. These features suggested
      that the immune response to OGDC is similar to that to exogenous antigen, and
      that the heavy and light chain variable regions of the anti-OGDC antibody undergo
      somatic hypermutation through antigen-driven clonal selection. This human mAb to
      OGDC, which was established for the first time from a patient with PBC and
      characterized at the molecular level, would be a valuable tool to study the B
      cell autoepitopes of OGDC, to clone as yet undetermined full length cDNA encoding
      OGDC and to dissect the autoimmune response to mitochondrial antigens in PBC.

PMID- 8527403
TI  - Comparison of peptide and superantigen-induced anergy in a peptide-specific
      polyclonal human T cell line.
AB  - T cells recognizing tetanus toxin peptide 'p2' (sequence 830-844) raised in HLA
      DR6 individuals preferentially express V beta 2 in the TCR. A p2-specific T cell
      line (60% V beta 2+) was used to compare peptide and superantigen [toxic shock
      syndrome toxin-1 (TSST-1)]-induced clonal anergy. Many experiments consistently
      revealed that the degree of 'tolerance' or 'clonal anergy' induced by peptide was
      greater than with the superantigen TSST-1. These results are of interest in a
      number of contexts. First they suggest that using superantigens or anti-V beta to
      delete the majority population of T cells may not be sufficient to diminish an
      autoimmune response. Secondly, the results indicate that induction of anergy of a
      large proportion of peptide-specific T cells does not lead to a suppressive
      bystander effect on the remaining responsive T cells. These results emphasize the
      need to define the dominant autoantigenic epitopes in human autoimmune diseases,
      since peptide based therapy such as the use of peptide analogues to induce anergy
      or a change in cytokine profile, is possibly more effective in controlling
      undesired immune responses than the use of non-antigen, TCR-directed approaches
      such as superantigens.

PMID- 8527404
TI  - Activation and re-activation potential of T cells responding to staphylococcal
      enterotoxin B.
AB  - To elucidate the parameters that lead to superantigen induced non-responsiveness,
      an in vitro model for studying primary and secondary responses to the bacterial
      superantigen staphylococcal enterotoxin B (SEB) was established. Upon re
      activation with SEB, in vitro SEB primed T cells show an early proliferative
      response that 'quenches' in time and is severely impaired 3 days after re
      stimulation. Despite their overall impaired proliferative capacity and IL-2
      production, these T cells are able to produce IFN-gamma and to up-regulate
      activation markers CD69 and IL-2R alpha upon re-stimulation with SEB,
      demonstrating that SEB non-responsiveness is not absolute. Rather, it reflects
      the inability to mount an ongoing proliferative response upon re-stimulation with
      SEB. Our results also demonstrate that SEB-induced non-responsiveness is not
      simply the result of presentation in the absence of co-stimulation, since
      presentation of SEB on highly purified dendritic cells during the primary
      response did not prevent the induction of non-responsiveness. As previously
      shown, SEB induces a Th1 phenotype in responding CD4+ T cells. Skewing towards a
      Th2 phenotype by adding IL-4 and antibodies to IFN-gamma did not prevent the
      induction of non-responsiveness by SEB. Interestingly, T cells pretreated with
      plate-bound anti-CD3 epsilon and anti-V beta 8 were also non-responsive to SEB re
      stimulation. Thus, non-responsiveness to SEB (defined here as inability to
      produce IL-2 and proliferate) seems to reflect an intrinsic inability of
      previously activated T cells to respond to SEB, probably reflecting differences
      in signal transduction pathways used by naive versus previously activated T
      cells.

PMID- 8527405
TI  - An MHC class II-expressing T cell clone presenting conventional antigen lacks the
      ability to present bacterial superantigen.
AB  - We have analyzed the response of rat T cells to myelin basic protein (MBP) and
      the bacterial superantigen, staphylococcal enterotoxin E (SEE). Rat T cells
      reactive with MBP can respond to SEE presented by spleen cells but not to SEE
      presented by LOA, a rat T cell clone that expresses both I-A and I-E MHC class II
      molecules, even though LOA is much more efficient than splenic APC in the
      presentation of MBP. The inability of LOA to present superantigen is not due to a
      structural difference in MHC II molecules between LOA and the splenic APC or to
      differential expression of major accessory/adhesion molecules, including CD2,
      CD5, CD4 and CD44, on LOA. The non-responsiveness of SEE/LOA-induced T cells
      differs from anergy, in that such cells do not lose their subsequent
      responsiveness to either MBP or SEE. Our results demonstrate that: (i) MHC class
      II molecules (I-A and I-E) alone are insufficient for the activation of T cells
      by bacterial superantigen, (ii) failure to respond to antigen presented upon
      inappropriate APC or in inadequate doses may not necessarily represent anergy,
      and (iii) the quality of the T cell response towards certain ligands can be
      strongly influenced by the nature of the APC.

PMID- 8527406
TI  - Molecular characterization of the pan-B cell antigen CDw78 as a MHC class II
      molecule by direct expression cloning of the transcription factor CIITA.
AB  - Antibodies against a pan-B cell-surface marker have been statistically clustered
      to define the CDw78 antigen. Molecular characterization of the CDw78 antigen was
      performed to determine its functional role in T and B cell interactions.
      Screening a direct expression cDNA library, made from the Epstein-Barr virus
      transformed, B lymphoblastoid cell line MP-1 with an anti-CDw78 mAb, we have
      isolated a 3.8 kb cDNA encoding the transcription factor CIITA, previously shown
      to transactivate human MHC class II expression. Using several anti-CD78 mAb, we
      observed induced expression of the CDw78 antigen on the surface of monkey CV
      1/EBNA cells transfected with the CIITA cDNA clone. Apparently, recombinant human
      CIITA can regulate the expression of monkey MHC class II which is recognized by
      anti-human CDw78 mAb. The anti-human CDw78 mAb seem to recognize a monomorphic
      determinant of MHC class II. Expression of recombinant human MHC class II
      antigens in CV-1/EBNA cells was recognized by a panel of CDw78 mAb, as well as by
      anti-human MHC class II mAb. These data show that the CDw78 antigen is expressed
      as part of the MHC class II molecule and appears similar if not identical to the
      alpha beta heterodimeric MHC class II antigen.

PMID- 8527407
TI  - BCMAp: an integral membrane protein in the Golgi apparatus of human mature B
      lymphocytes.
AB  - BCMA is a human gene expressed preferentially in mature B lymphocytes as a 1.2 kb
      mRNA, which encodes a 184 amino acid peptide (BCMAp). The study of BCMA mRNA
      expression, using human malignant B cell lines characteristic of different stages
      of B lymphocyte differentiation, demonstrated that the BCMA mRNA is absent in the
      pro-B lymphocyte stage. It is expressed faintly at the pre-B cell stage and its
      expression increases with B lymphocyte maturation. Polyclonal antibodies were
      used to show, by cellular fractionation and immunoprecipitation, that BCMAp is a
      non-glycosylated integral membrane protein. Furthermore, BCMAp inserts, in vitro,
      into canine microsomes, as a type I integral membrane protein. Cell surface
      labeling showed that BCMAp is not expressed in the plasma membrane of mature B
      lymphocytes. Immunofluorescence studies revealed that BCMAp lies in a cap-like
      structure near the nucleus, that was identified as the Golgi apparatus by co
      localization of BCMAp with CTR433, a marker of the medial cisternae of the Golgi
      apparatus. Confocal scanning laser microscopy of U266 plasma cells labeled with
      markers of various Golgi apparatus subcompartments strongly suggests that BCMAp
      is located in the cis part of the Golgi apparatus. Thus, BCMAp is the first Golgi
      resident protein with a tissue specificity and whose expression is linked to the
      stage of differentiation of B lymphocytes. The location of BCMAp in the Golgi
      apparatus and its high expression in plasmocytes (secreting large amounts of Ig)
      suggest that BCMAp is implicated in the intracellular traffic of Ig.

PMID- 8527408
TI  - Anti-inflammatory effects of sulfatides in selectin-dependent acute lung injury.
AB  - Selectins promote adhesive interactions between leukocytes and activated
      endothelial cells, the adhesion being mediated by 'counter-receptors' on
      endothelial cells and consisting of oligosaccharide conjugates containing sialic
      acid and fucose. There are also suggestions that selectins bind sulfated
      compounds, including sulfatides. Intravenous infusion of selectin-reactive
      oligosaccharides has been found to prevent selectin-dependent inflammatory lung
      injury. In the current studies using two models of neutrophil and selectin
      dependent acute lung injury in rats, sulfatide and its modified versions were
      infused i.v. and the protective effects determined. Naturally occurring
      sulfatide, synthetic sulfatides and sulfated ganglioside were highly protective
      against lung injury following systemic activation of complement. Desulfated
      sulfatide was inactive. The protective effects of synthetic sulfatides required
      sulfation of galactose in position 3. Sulfatide was also protective in the IgG
      immune complex model of lung injury. The protective effects of sulfatides were
      associated with reduced content of myeloperoxidase (derived from neutrophils) in
      lung tissue. These data indicate that sulfatides have significant in vivo
      protective effects in neutrophil and selectin-dependent models of lung injury.

PMID- 8527409
TI  - Functional CD4+ T cell subsets defined by expression of CD45RC and NTA260
      antigens and age-associated polarization in murine lupus.
AB  - Using two mAb, one specific to the alternative exon 6-dependent epitope of CD45
      molecules (JH6.2) and one a natural thymocytotoxic autoantibody (NTA) with an
      unknown reactive epitope (NTA260), we subdivided splenic CD4+ T cells from 2
      month-old BALB/c mice into five phenotypically distinct subsets. CD45RC+NTA260-
      (S I) cells were phenotypically analogous to CD4+ T cells predominating in
      newborn mice and produced a significant amount of IL-2, but not so IL-4, IL-10 or
      IFN-gamma when stimulated with immobilized anti-CD3 mAb in vitro. They appeared
      to consist mainly of naive ThP cells. The CD45RC+NTA260+ (S II) subset also
      produced IL-2, but not other cytokines; however, the IL-2 levels produced were
      much higher than seen with the S I subset, thereby suggesting the predominance of
      further maturated ThP cells. The CD45RC-NTA260+ (S III) subset mainly produced IL
      4, IL-10, IFN-gamma and less IL-2, and contained memory cells that helped the
      secondary antibody response to a recall antigen, and hence contained Th2 and
      probably a mixture of Th0 and Th1 cells. The CD45RC-NTA260- (S IV) subset was a
      poor responder to the immobilized anti-CD3 mAb. The CD45RCbrightNTA260dull (S V)
      subset consisted of a small number of cells that were phenotypically analogous to
      activated CD4+ T cells. While an age-associated decrease in the proportion of S I
      and less markedly in S II and in turn increase in S III subsets of CD4+ T cells
      occurred in normal BALB/c mice, autoimmune disease-prone (NZB x NZW)F1 mice
      showed a marked age-associated decrease in the proportion of not only S I, II but
      also III subsets. As aged (NZB x NZW)F1 mice carry CD4+ T helper cells for IgG
      anti-DNA antibody production, such age-associated polarization to the S IV subset
      appears to be critical in the pathogenesis of autoimmune disease in these mice.

PMID- 8527410
TI  - IgG isotype-specific auto-antibodies bind preferentially to cross-linked membrane
      Ig.
AB  - Under equilibrium conditions, the affinities of five anti-IgG2a mAb isolated from
      virus-infected mice were comparable to other high-affinity auto-antibodies.
      Similar to rheumatoid factors, these anti-IgG2a auto-antibodies bound to
      aggregated or complexed IgG2a with 50 to 1500-fold higher avidity than their
      monomeric counterparts. Despite their high functional affinity to IgG2a, flow
      cytometric analysis revealed no binding or marginal mAb binding to four distinct
      lines of B cells expressing different densities of membrane-anchored IgG2a. If,
      however, surface IgG2a was cross-linked by polyclonal light chain-specific
      antibodies, IgM and IgA mAb binding resulted, and was detected as an increase in
      mean fluorescence intensity compared with isotype-matched control antibodies. The
      binding of one IgM mAb to cross-linked IgG2a patches of the cell surface was also
      visualized by confocal microscopy. Pretreatment of cells with aggregated IgG2a
      caused increased fluorescence intensity, demonstrating that the IgM and IgA mAb
      were also able to interact with IgG2a aggregates bound on the B cell surface via
      Fc gamma RIIB. It also permitted efficient co-ligation of the aggregated B cell
      receptors (BCR) with Fc gamma RIIB-fixed immune complexes known to deliver a
      negative signal in B cell activation. Cross-linking of IgG2a complexes bound to
      Fc gamma RI on macrophages or dendritic cells with antigen-specific BCR and/or T
      cells via their Fc gamma RIIB may accelerate the physical contact of cells
      involved in the antigen-specific response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527411
TI  - Systemic administration of rIL-12 induces complete tumor regression and
      protective immunity: response is correlated with a striking reversal of
      suppressed IFN-gamma production by anti-tumor T cells.
AB  - Unfractionated spleen cells taken from tumor-bearing mice 2 weeks after tumor
      implantation contained tumor-primed T cells which produced cytokines including IL
      2 and IFN-gamma when cultured in vitro. With progressive tumor growth this
      initial lymphokine-producing capacity decreased. Here, we investigated the
      ability of IL-12 to (i) restore suppressed IFN-gamma production, (ii) cause tumor
      regression and (ii) induce anti-tumor protective immunity. Addition of rIL-12 to
      spleen cell cultures from 4- to 10-week-old tumor-bearing mice resulted in a
      striking enhancement in the production of IFN-gamma compared with cultures of
      these cells in the absence of rIL-12 or of normal spleen cells in the presence of
      rIL-12. Five i.p. injections of rIL-12 into mice bearing s.c. tumors induced
      complete tumor regression. This was found when rIL-12 was given at early (1-2
      weeks), intermediate (4-5 weeks) or even late (7 weeks) stages of tumor growth.
      Furthermore, IL-12-treated mice which rejected the primary tumor exhibited
      complete resistance to a rechallenge with the same tumor but did not reject a
      second syngenetic tumor. Immunohistochemical analyses following IL-12 treatment
      revealed that CD4+ and CD8+ T cells infiltrate the tumor. More importantly, IFN
      gamma mRNA expression was observed in fresh tumor masses from tumor-bearing mice
      receiving IL-12 treatment. The importance of IFN-gamma was further demonstrated
      by the observation that the systemic administration of anti-IFN-gamma mAb prior
      to IL-12 treatment completely abrogated the anti-tumor effect of IL-12. Thus,
      these results indicate that administration of modest levels of rIL-12 to tumor
      bearing mice results in tumor regression through mechanisms involving reversal of
      suppressed IFN-gamma production by anti-tumor T cells and the establishment of a
      tumor-specific protective immune response.

PMID- 8527412
TI  - Expression of a TCR V beta 8.2 polypeptide from the unrearranged gene in a murine
      lymphoid precursor cell line.
AB  - The TCR in a mature T cell is a multimeric complex of TCR alpha and beta chains,
      and CD3 subunits. Functional TCR alpha and beta chains are encoded by genes that
      result from developmentally controlled somatic rearrangement events. By FACS
      analysis, we have detected a TCR V beta 8 protein on the surface of an immature
      lymphoid cell line, C1-V13D, that has all of its TCR genes in germline
      (unrearranged) configuration. RNA blot analysis detected a 1.4 kb polydenylated V
      beta 8 RNA in C1-V13D cells, but no expression of C beta was detected. Rapid
      amplification of 3' cDNA ends was used to clone an RNA that was initiated from
      the leader exon of the V beta 5.1 gene and spliced to the V exon of the V beta
      8.2 gene. The putative sequence of the mature 10.8 kDa protein was entirely
      encoded by the V beta 8.2 exon. RT-PCR analysis confirmed that 97% of the V beta
      8 RNA detected in C1-V13D cells was encoded by the V beta 8.2 gene, and only 3%
      by V beta 8.1 and V beta 8.3 genes. Furthermore, most of the V beta 8.2 RNA was
      spliced to the leader exon of the V beta 5.1 gene and not to the leader exon of
      the V beta 8.2 gene. The implications of preferential transcription from
      particular germline TCR genes for repertoire diversity and possible functions for
      proteins translated from germline TCR V beta genes are discussed.

PMID- 8527413
TI  - Predominant expression of invariant V alpha 14+ TCR alpha chain in NK1.1+ T cell
      populations.
AB  - A novel T cell subset characterized by cell surface NK1.1+ TCR alpha beta+
      expression was investigated for its TCR alpha usage, particularly that of
      invariant V alpha 14 TCR, which was found to be preferentially used in peripheral
      CD4-CD8- T cells developed at extrathymic sites. We found that NK+ alpha beta T
      cell subsets account for 0.4% in thymocytes, 5% in the splenic T cells and 40.5%
      in the bone marrow T cells. Among these NK+ alpha beta T cells, two distinct
      subsets were detected; cell surface TCR V alpha 14+ and V alpha 14-
      subpopulations. Almost all of NK+ alpha beta thymocytes express V alpha 14 mRNA;
      however, only < 20% were positive, while > 80% were negative or undetectable for
      V alpha 14 TCR expression on the cell surface in the thymus. Similarly,
      approximately 50% of NK+ alpha beta T cells in spleen and bone marrow are V alpha
      14+ as revealed by FACS. TCR repertoire analysis by nucleotide sequences on
      inverse PCR products demonstrated that most NK+ alpha beta T cells express an
      invariant TCR encoded by the V alpha 14J alpha 281 gene with a 1 base N-region in
      all tissues. Thus, invariant V alpha 14 TCR is uniquely expressed on NK T cells,
      and can be a marker to distinguish NK, NK T and T cells.

PMID- 8527414
TI  - Molecular modeling studies of the artemisinin (qinghaosu)-hemin interaction:
      docking between the antimalarial agent and its putative receptor.
AB  - Artemisinin (qinghaosu, QHS) is a promising new antimalarial agent that is
      effective against drug-resistant strains of malaria. The antimalarial activity of
      this drug appears to be mediated by an interaction of the drug's endoperoxide
      bridge with intraparasitic hemin. We have carried out a computer-assisted docking
      of QHS with hemin from various starting configurations and found that, in the
      most stable docked configuration, the endoperoxide bridge is in close proximity
      to the hemin iron. In contrast, an inactive analog, deoxyartemisinin (DQHS),
      docks in a different manner. Further computer analysis of the drug-hemin
      interaction might aid in the design of new QHS congeners.

PMID- 8527415
TI  - 1994 Molecular Graphics Art Show and Video Show.
AB  - The 1994 Molecular Graphics Art Show and Video Show were presented at the 13th
      annual international meeting of the Molecular Graphics and Modelling Society. The
      art show--shown in the Mary & Leigh Block Gallery on the campus of Northwestern
      University, Evanston, Illinois--included original artworks by eighteen artists
      and the video show included nine original animated works. All were chosen for
      their ability to present the complexity, diversity, and beauty of the molecular
      world in visual form. Works from a wide range of disciplines were represented,
      including work by scientists actively involved in structural research, by
      commercial illustrators presenting these results to students and physicians, and
      by fine artists exploring the meanings and implications of these molecules in our
      lives. Included in this issue of the Journal of Molecular Graphics are comments
      by the juror of the show, T.J. O'Donnell, a catalogue of the art show, and a
      catalogue of the video show.

PMID- 8527416
TI  - Navigator: tools for informal structure-activity relationship discovery.
AB  - Navigator is a molecular database visualization system, designed to support
      exploratory data analysis and informal structure-activity relationship studies.
      In addition to the operations commonly found in chemical database systems, it
      provides new tools that facilitate substituent analysis and help elucidate the
      relationships among similar molecules and between related assays. Navigator's
      capabilities include two ways of displaying the relationships between analogs,
      mouse-sensitive charts of sets of molecules, mouse-sensitive plots of assay
      relationships, and access to a system for three-dimensional quantitative
      structure-activity relationship discovery. Navigator's mouse-based user interface
      provides a one-object/one-window paradigm that makes data manipulation easy even
      for inexperienced users. Navigator runs on Silicon Graphics workstations.

PMID- 8527417
TI  - Approximation and visualization of large-scale motion of protein surfaces.
AB  - We present a method for the approximation and real-time visualization of large
      scale motion of protein surfaces. A molecular surface is represented by an
      expansion of spherical harmonic functions, and the motion of protein atoms around
      their equilibrium positions is computed by normal mode analysis. The motion of
      the surface is approximated by projecting the normal mode vectors of the solvent
      accessible atoms to the spherical harmonic representation of the molecular
      surface. These surface motion vectors are represented by a separate spherical
      harmonic expansion. Representing the surface geometry and the surface motion
      vectors by spherical harmonic expansions allows variable-resolution analysis and
      real-time display of the large-scale surface motion. This technique has been
      applied to interactive visualization, interactive surface manipulation, and
      animation.

PMID- 8527418
TI  - Texture mapping parametric molecular surfaces.
AB  - Texture mapping is an increasingly popular technique in molecular modeling. It is
      particularly effective in representing high-resolution surface detail using a low
      resolution polygonal model. We describe how texture mapping can be used with
      parametric molecular surfaces represented as expansions of spherical harmonic
      functions. We define analytically the texture image and its transformation to a
      parametric surface. Unlike most methods of texture mapping, this transformation
      defines a one-to-one correspondence between the surface and the texture; texture
      coordinates are derived from the location of the surface point and not from
      physical properties at the surface point. This has advantages for the interactive
      visualization of surface data. We control the interactive response time by
      lowering the resolution of the polygon mesh while retaining the high-resolution
      detail of the texture, or we can lower the resolution of the texture image with
      the same polygonal model. By using a well-defined convention for texture
      coordinates, we can use the same image for the original surface or its parametric
      representation, and we can rapidly switch between images that represent different
      surface properties without recomputing the texture coordinates. Parametric
      surfaces allow new flexibility for the visualization of molecular surface data.

PMID- 8527419
TI  - Clinical and basic science aspects of the biopsychosocial model.

PMID- 8527420
TI  - The 18th annual meeting of the Canadian College of Neuropsychopharmacology in
      Association with the Japanese Society of Neuropsychopharmacology. Vancouver,
      Canada, June 4-7, 1995.

PMID- 8527421
TI  - Steroid effects on brain functions: an example of the action of glucocorticoids
      on central dopaminergic and neurotensinergic systems.
AB  - It is now clearly established that steroid hormones released from peripheral
      endocrine glands may, through specific receptors in the brain, directly regulate
      brain function. These effects may be rapid or involve long-term modifications at
      the genomic level. Concerning the glucocorticoids, their receptors are found in
      most neuronal cells, an observation which can be related to their widespread
      effects on neuronal metabolism. Furthermore, glucocorticoids are often related to
      stress. We have previously demonstrated that neonatal handling of the rat
      prevented excessive endocrine response to stress. In adults, this action appeared
      to protect the animal from potential damaging effects of glucocorticoids and from
      related impairment of cognitive functions. The effects of glucocorticoids are
      thought to involve an interaction of several central neurotransmitter systems.
      One such neurotransmitter is neurotensin, a neuropeptide which was reported to be
      closely related to central dopaminergic system regulation. This paper presents a
      rapid overview of the central effects of glucocorticoids and possible evidence
      for the interrelationship between these steroids, dopamine and neurotensin
      systems in the regulation of the hypothalamo-pituitary-adrenal axis. It provides
      a new way to approach stress responses and to develop new substances that may
      become potential drugs in the treatment of some psychiatric disorders.

PMID- 8527422
TI  - [Interleukin-1 receptors in the central nervous system: role in infection and in
      stress].

PMID- 8527423
TI  - Dopamine and GABAA receptor imbalance after ovariectomy in rats: model of
      menopause.
AB  - A peak of first episodes of schizophrenia can occur in postmenopausal women.
      Furthermore, tardive dyskinesia is more common in postmenopausal women than in
      men of comparable age. This study investigated the effect of ovariectomy (2 weeks
      or 3 months) in rats as a model of decreased gonadal function associated with
      menopause. After ovariectomy, frontal cortex D1 receptors progressively decreased
      in density with no change of affinity over time. Striatal D1 and D2 receptors
      also had decreased density after ovariectomy with no change of affinity. In the
      substantia nigra pars reticulata, a progressive increase in [3H]flunitrazepam
      specific binding associated with GABAA receptors was observed as a function of
      time following ovariectomy. It is hypothesized that low prefrontal cortex
      dopamine activity has implications in negative symptoms of schizophrenia and,
      furthermore, that GABAergic overactivity in the internal globus pallidus
      substantia nigra pars reticulata complex plays a role in tardive dyskinesia. The
      present results suggest that, by reducing brain dopamine receptors and increasing
      GABAA receptors, gonadal hormone withdrawal may predispose to schizophrenia and
      dyskinesia.

PMID- 8527425
TI  - Spatial cognition in humans: possible modulation by androgens and estrogens.
AB  - Many studies in nonhuman species have shown that gonadal steroid hormones can
      influence the regional structure and physiology of the central nervous system,
      and can bring about both short- and long-term effects on behavior. The extent to
      which human behavior and thought processes are subtly influenced by the hormonal
      milieu is unclear. There is preliminary evidence from a number of clinical
      endocrine syndromes, and from studies of normal human subjects, that sex steroids
      may modulate the expression of certain specific cognitive abilities. This paper
      will briefly review some recent evidence suggesting that visual-spatial abilities
      are among the cognitive functions that may be affected.

PMID- 8527424
TI  - Alcoholism: the role of different motivational systems.
AB  - Individuals use and misuse alcohol (and other drugs) because of the
      pharmacologically mediated effects these substances have on the operation of 4
      psychobiological systems, mediating response to motivationally relevant
      unconditioned and conditioned stimuli. These 4 systems have unique
      neuroanatomical structure, biochemical modes of operation, association with
      affect, behavior and cognition, and responsiveness to drugs of abuse. Individual
      variation in the operation of these systems determines individual susceptibility
      to initiation and maintenance of drug use and abuse. Sources of such variation
      differ, in a vitally important fashion, in various specific populations of
      individuals at heightened risk for drug abuse. Nonalcoholic sons of male
      alcoholics, with multigenerational family histories of male alcoholism, appear to
      be at heightened risk for the development of alcohol abuse because alcohol
      eliminates their heightened response to threat, and because they are
      hypersensitive to ethanol's psychomotor stimulant effects. Anxiety-sensitive
      individuals also appear attracted to alcohol for its anxiolytic properties. Many
      other important sources of idiosyncratic variability exist. Detailed analysis of
      such sources may lead to the development of more effective prevention and
      treatment programs.

PMID- 8527426
TI  - Coordination of the Rieske-type [2Fe-2S] cluster of the terminal iron-sulfur
      protein of Pseudomonas putida benzene 1,2-dioxygenase, studied by one- and two
      dimensional electron spin-echo envelope modulation spectroscopy.
AB  - One- and two-dimensional (1D and 2D) electron spin-echo envelope modulation
      (ESEEM) spectroscopy has been used to investigate the ligand environment of the
      [2Fe-2S] cluster from the terminal dioxygenase (ISPBED) of the Pseudomonas putida
      benzene dioxygenase complex. The modulation frequencies observed in the 0.5-8.5
      MHz region of the Fourier transforms of 1D and 2D ESEEM spectra measured across
      the electron paramagnetic resonance (EPR) absorbance envelope (from gz through to
      gx) are consistent with their assignment to two 14N nuclei. Using hyperfine
      sublevel correlation spectroscopy (HYSCORE), two sets of correlated double
      quantum transitions sharing the same hyperfine coupling were observed and were
      identified as being due to the same two 14N nuclei. On the basis of the isotropic
      hyperfine and quadrupolar couplings estimated for these 14N nuclei [N(1), Aiso =
      3.6 MHz and e2qQ = 2.2-2.8 MHz; N(2), Aiso = 4.8 MHz and e2qQ = 2.2-2.4 MHz], the
      ESEEM pattern of ISPBED is assigned to two histidine nitrogens which are directly
      coordinated to the reduced iron-sulfur cluster. Bonding parameters of the two
      [14N]histidine ligands were calculated from these hyperfine couplings. The
      primary covalent contributions to the hyperfine interaction arise from 14N-to
      Fe2+ sigma bonds. For N(1), our analysis of the percentage of unpaired 2s and 2p
      electrons gave f2s approximately 1.3% and f2p approximately 0.2%, while values of
      f2s approximately 1.7% and f2p approximately 1.4% were estimated for N(2).
      Comparison of these values with those determined from electron nuclear double
      resonance (ENDOR) data of the Rieske-type [2Fe-2S] center of Pseudomonas cepacia
      phthalate dioxygenase [Gurbiel, R. J., Batie, C. J., Sivaraja, M., True, A. E.,
      Fee, J. A., Hoffman, B. M., & Ballou, D. P. (1989) Biochemistry 28, 4861-4871]
      indicates an apparent reduction in unpaired electron spin density residing on the
      two 14N ligands of ISPBED. Analysis of slices of the HYSCORE spectrum has
      provided evidence for another 14N nucleus (A approximately 1.1 MHz, e2qQ = 3.3
      MHz), which we have attributed to a weakly coupled peptide nitrogen, similar to
      those observed for ferredoxin-type [2Fe-2S] clusters. This type of weak
      interaction has not been previously described by the detailed ENDOR and ESEEM
      studies of Rieske-type centers. The resolution of the spectra demonstrates the
      effectiveness of 2D ESEEM for the disentanglement of multiple hyperfine
      interactions to metalloprotein centers.

PMID- 8527427
TI  - Is the continuity of the domains required for the correct folding of a two-domain
      protein?
AB  - The role of domains in protein folding has been widely studied and discussed.
      Nevertheless, it is not clear whether the continuity of the domains in a protein
      is an essential requirement in determining the folding pathway. Previous studies
      have shown that the isolated structural domains of the two-domain monomeric
      enzyme, yeast phosphoglycerate kinase (yPGK), are able to fold independently into
      a quasinative structure, but they neither reassociate nor generate a functional
      enzyme [Minard, P., Hall, L., Betton, J. M., Missiakas, D., & Yon, J. M. (1989)
      Protein Eng. 3, 55-60; Fairbrother, W. J., Bowen, D., Hall, L., Williams, R. J.
      P. (1989) Eur. J. Biochem. 184, 617-625; Missiakas, D., Betton, J. M., Minard,
      P., & Yon, J. M. (1990) Biochemistry 29, 8683-8689]. In the present work, two
      circularly permuted variants of the yPGK gene were constructed. The natural
      adjacent chain termini were directly connected and the new extremities were
      created within the N-domain (at residues 71 and 72) or the C-domain (at residues
      291 and 292), respectively. These two proteins were overexpressed and purified.
      They exhibit 14% and 23% of the wild-type enzyme activity, respectively. The two
      mutants fold in a compact conformation with slight changes in the secondary and
      tertiary structure probably related to the presence of a heterogeneous population
      of molecules. The unfolding studies reveal a large decrease in stability. From
      the present data it appears that, although the circular permutations induce some
      perturbations in the structure and stability of the protein, the continuity of
      the domains is not required for the protein to reach a native-like and functional
      structure.

PMID- 8527428
TI  - Folding pathway of Escherichia coli ribonuclease HI: a circular dichroism,
      fluorescence, and NMR study.
AB  - The unfolding and refolding processes of Escherichia coli ribonuclease HI at 25
      degrees C, induced by concentration jumps of either guanidine hydrochloride
      (GuHCl) or urea, were investigated using stopped-flow circular dichroism (CD),
      stopped-flow fluorescence, and NMR spectroscopies. Only a single exponential
      process was detected for the fast time scale unfolding (rate constants from 0.014
      to 0.54 s-1, depending on the final denaturant concentration). For refolding, the
      far-UV CD value largely recovered within 50 ms of the stopped-flow mixing dead
      time (burst phase). This phase was followed by either one or two phases, with
      rate constants from 0.035 to 2.45 s-1 as detected by CD and fluorescence,
      respectively. Although this protein has a single cis-Pro residue, a very slow
      phase due to proline isomerization was not observed, for either unfolding or
      refolding. The difference in the amplitudes of the burst phases for refolding in
      the far- and near-UV CD spectra revealed that an intermediate state exists, with
      the characteristics of a molten globule. Because the one-phased fast exponential
      process detected by CD corresponds to the slower of the two phases detected by
      fluorescence, the intermediate detected by CD might be the most stable. GuHCl
      denaturation experiments revealed that this intermediate cooperatively unfolds,
      with a transition midpoint of 1.33 +/- 0.03 M. The Gibbs free energy difference
      (delta G) between the intermediate and the unfolded states, under physiological
      conditions (25 degrees C, pH 5.5, and 0 M GuHCl), was estimated to be 20.0 +/-
      2.3 kJ mol-1. Therefore, it is reasonable to assume that the refolding
      intermediate, rather than the unfolded state, is the latent denatured state under
      physiological conditions. Approximately linear relationships between the GuHCl
      concentration and the logarithm of the microscopic rate constants determined by
      CD and fluorescence were also observed. By extrapolation to a GuHCl concentration
      of 0 M, activation Gibbs free energies of 98.5 +/- 1.1 kJ mol-1 for unfolding and
      69.5 +/- 0.2 kJ mol-1 for refolding under physiological conditions were obtained.
      The hydrogen-exchange-refolding competition combined with two-dimensional NMR
      revealed that the amide protons of alpha-helix I are the most highly protected,
      suggesting that alpha-helix I is the initial site of protein folding. The CD and
      NMR data showed that the intermediate state has a structure similar to that of
      the acid-denatured molten globule.

PMID- 8527429
TI  - Determination of the three-dimensional solution structure of noxiustoxin:
      analysis of structural differences with related short-chain scorpion toxins.
AB  - The 3D structure of noxiustoxin, the first identified scorpion toxin acting on K+
      channels, has been elucidated by NMR and molecular modeling. Thirty-nine solution
      structures were calculated using 572 distance and 42 dihedral restraints. The
      average atomic rms deviation between the refined structures and the mean
      structure is 0.75 A for the backbone atoms. Noxiustoxin adopts a alpha/beta
      scaffold constituted of a three-stranded beta-sheet (residues 2-3, 25-30, 33-38)
      linked to a helix (residues 10-20) through two disulfide bridges. A comparison
      between the 3D structure of noxiustoxin and those of other structurally and
      functionally related scorpion toxins (charybdotoxin, PO5-NH2, kaliotoxin)
      revealed a bending capacity of the helix and a variability in the relative
      orientations between the helix and the beta-sheet. These two features highlight
      the plasticity of the alpha/beta scaffold and offer a structural explanation for
      the capacity of the fold to accommodate an additional alanine residue in the Gly
      x-Cys pattern of a previously proposed consensus sequence [Bontems et al. (1991)
      Science 254, 1521-1523]. Our structural data also emphasize the possibility that
      the beta-sheet of NTX is implicated in the capacity of NTX to recognize voltage
      dependent K+ channels.

PMID- 8527430
TI  - Solution structure of a band 3 peptide inhibitor bound to aldolase: a proposed
      mechanism for regulating binding by tyrosine phosphorylation.
AB  - Human erythrocyte band 3 inhibits glycolytic enzymes, including aldolase, by
      binding these cytoplasmic enzymes at its N-terminus. Phosphorylation of Y8
      disrupts inhibition, and there is evidence that in vivo glycolysis levels in
      erythrocytes are regulated in part by a phosphorylation/dephosphorylation
      signaling pathway. The structural basis for control by phosphorylation has been
      investigated by NMR studies on a complex between aldolase and a synthetic peptide
      corresponding to the first 15 residues of band 3 (MEELQDDYEDMMEEN-NH2). The
      structure of this band 3 peptide (B3P) when it is bound to rabbit muscle aldolase
      was determined using the exchange-transferred nuclear Overhauser effect (ETNOE).
      Two hundred NMR structures for B3P were generated by simulated annealing
      molecular dynamics with NMR-derived distance restraints and excluding
      electrostatic terms. Twenty structures were further refined against a force field
      including full partial charges. The important conformational feature of B3P in
      the bound state is a folded loop structure involving residues 4-9 and M12 that
      surrounds Y8 and is stabilized by a hydrophobic cluster with the ring of Y8
      sandwiched between the methyl groups of L4 and M12. Differential line broadening
      indicates that this loop structure binds aldolase in a relatively specific
      manner, while terminal regions are structurally heterogeneous. To better
      understand B3P inhibition of aldolase and the mechanism of phosphorylation
      control, a complex was modeled by docking B3P into the active site of aldolase
      and optimizing the fit using restrained molecular dynamics and energy
      minimization. The B3P loop is complementary in conformation to the beta-barrel
      central core containing the aldolase active site residues. Binding is
      electrostatic in nature with numerous ionic and hydrogen-bonding interactions
      involving several conserved lysine and arginine residues of aldolase. How
      phosphorylation of band 3 could disrupt inhibition was considered by modeling a
      phosphoryl moiety onto Y8 of B3P. An energetic analysis with respect to rigid
      phosphate rotation suggests that aldolase inhibition is reversed primarily
      because of electrostatic repulsion between B3P residues that destabilizes the B3P
      loop formed in the complex. This proposed intramolecular mechanism for blocking
      protein--protein association by electrostatic repulsion with the phosphoryl group
      may be applicable to other protein--protein signaling complexes.

PMID- 8527431
TI  - 2 A resolution structure of DppA, a periplasmic dipeptide transport/chemosensory
      receptor.
AB  - The family of about 50 periplasmic binding proteins, which exhibit diverse
      specificity (e.g., carbohydrates, amino acids, dipeptides, oligopeptides,
      oxyanions, metals, and vitamins) and range in size from 20 to 58 kDa, is a gold
      mine for an atomic-level investigation of structure and molecular recognition.
      These proteins serve as initial receptors for active transport systems or
      permeases. About six of these proteins, including the dipeptide-binding protein
      (DppA), are also primary receptors for chemotaxis. The structure of the unbound
      form of DppA (M(r) = 57,400) has been determined and refined to an R-factor of
      0.169 to 2 A resolution. DppA consists of two distinct domains (I and II)
      connected by two "hinge" segments which form part of the base of the wide groove
      between the two domains. The relative orientation of the two domains gives the
      protein a pearlike shape, with domain I and domain II forming the larger and
      smaller apical ends, respectively. From the tip to the rounded bottom measures
      about 85 A, and the widest diameter is about 60 A. Domain I, which consists of
      two integrated subdomains, is folded from two separate polypeptide segments from
      the amino- and carboxyl-terminal ends. The more compact domain II is formed from
      the intervening segment. Comparison of the dipeptide-binding protein structure
      with that of the bound form of the similar oligopeptide-binding protein [Tame, J.
      R. H., Murshudov, G. N., Dodson, E. J., Neil, T. K., Dodson, G. G., Higgins, C.
      F., & Wilkinson, A. J. (1994) Science 264, 1578-1581] reveals the major features
      that differentiate the ligand specificity of the two proteins and describe the
      large hinge bending (about 55 degrees) between the two domains.

PMID- 8527432
TI  - Structure of the A-domain of HMG1 and its interaction with DNA as studied by
      heteronuclear three- and four-dimensional NMR spectroscopy.
AB  - HMG1 has two homologous, folded DNA-binding domains ("HMG boxes"), A and B,
      linked by a short basic region to an acidic C-terminal domain. Like the whole
      protein, which may perform an architectural role in chromatin, the individual
      boxes bind to DNA without sequence specificity, have a preference for distorted
      or prebent DNA, and are able to bend DNA and constrain negative superhelical
      turns. They show qualitatively similar properties with quantitative differences.
      We have previously determined the structure of the HMG box from the central B
      domain (77 residues) by two-dimensional NMR spectroscopy, which showed that it
      contains a novel fold [Weir et al. (1993) EMBO J. 12, 1311-1319]. We have now
      determined the structure of the A-domain (as a Cys-->Ser mutant at position 22 to
      avoid oxidation, without effect on its DNA-binding properties or structure) using
      heteronuclear three- and four-dimensional NMR spectroscopy. The A-domain has a
      very similar global fold to the B-domain and the Drosophila protein HMG-D [Jones
      et al. (1994) Structure 2, 609-627]. There are small differences between A and B,
      in particular in the orientation of helix I, where the B-domain is more similar
      to HMG-D than it is to the A-domain; these differences may turn out to be related
      to the subtle differences in functional properties between the two domains [Teo
      et al. (1995) Eur. J. Biochem. 230, 943-950] and will be the subject of further
      investigation. NMR studies of the interaction of the A-domain of HMG1 with a
      short double-stranded oligonucleotide support the notion that the protein binds
      via the concave face of the L-shaped structure; extensive contacts with the DNA
      are made by the N-terminal extended strand, the N-terminus of helix I, and the C
      terminus of helix II. These contacts are very similar to those seen in the LEF-1
      and SRY-DNA complexes [Love et al. (1995) Nature 376, 791-795; Werner et al.
      (1995) Cell 81, 705-714].

PMID- 8527433
TI  - Backbone dynamics of the A-domain of HMG1 as studied by 15N NMR spectroscopy.
AB  - The HMG-box sequence motif (approximately 80 residues) occurs in a number of
      abundant eukaryotic chromosomal proteins such as HMG1, which binds DNA without
      sequence specificity, but with "structure specificity", as well as in several
      sequence-specific transcription factors. HMG1 has two such boxes, A and B, which
      show approximately 30% sequence identity, and an acidic C-terminal tail. The
      boxes are responsible for the ability of the protein to bend DNA and bind to bent
      or distorted DNA. The structure of the HMG box has been determined by NMR
      spectroscopy for the B-domain of HMG1 [Weir et al. (1993) EMBO J. 12, 1311-1319;
      Read et al. (1993) Nucleic Acids Res. 21, 3427-3436) and for Drosophila HMG-D
      (Jones et al. (1994) Structure 2, 609-627]. It has an unusual twisted L-shape,
      suggesting that the protein might tumble anisotropically in solution. In this
      paper we report studies of the A-domain from HMG1 using 15N NMR spectroscopy
      which show that the backbone dynamics of the protein can be described by two
      different rotational correlation times of 9.0 +/- 0.5 and 10.8 +/- 0.5 ns. We
      show that the relaxation data can be analyzed by assuming that the protein is a
      rigid, axially symmetric ellipsoid undergoing anisotropic rotational diffusion;
      the global rotational diffusion constants, D parallel and D perpendicular, were
      estimated as 2.47 x 10(7) and 1.49 x 10(7) s-1, respectively. By estimating the
      angle between the amide bond vectors and the major axis of the rotational
      diffusion tensor from the family of structures determined by NMR spectroscopy
      [see accompanying paper, Hardman et al. (1995) Biochemistry 34, 16596-16607], we
      were able to show that the ellipsoid spectral density equation can reproduce the
      major features of the 15N T1 and T2 profiles of the three helices in the HMG1 A
      domain. The backbone dynamics of the A-domain were then compared with those of
      the B-domain and the HMG box from HMG-D. This comparison strongly supported the
      differences observed in the orientation of helix I in the three structures, where
      the B-domain appears to be more similar to HMG-D than it is to the A-domain.
      These differences may turn out to be related to subtle differences in the DNA
      binding properties of the A- and B-domains of HMG1.

PMID- 8527434
TI  - Sugar conformations in DNA and RNA-DNA triple helices determined by FTIR
      spectroscopy: role of backbone composition.
AB  - We have studied the effect of the nature of the third-strand sugar (ribose or
      deoxyribose) on the geometry and stability of triple helices with a pyrimidine
      motif targeting the polypurine tract of the Friend murine retrovirus. Comparison
      between triplexes containing a third strand formed by a deoxy 13mer d(TCT5C6),
      the same oligomer but with C5-methylated cytosines d(T5meCT5(5me)C6), and an
      analogous modified 13mer RNA 2'Omer(UCU5C6) shows that the sugar conformations of
      the different triple helices, determined by FTIR spectroscopy, differ depending
      on nature of the third-strand sugar. Pyrimidine*purine-pyrimidine triple-helix
      formation with the third-strand RNA and the duplex as DNA appears to be
      associated with a conversion of the duplex part from a B-form secondary structure
      with S-type sugars to a geometry in which the polypurine strand sugars adopt an N
      type conformation. Thermal dissociation of the triplexes was studied by UV
      absorbance spectroscopy. The most stable triple helix is obtained when the third
      strand contains 2'-O-methylated ribose sugars.

PMID- 8527435
TI  - Evidence for distinct ligand-bound conformational states of the multifunctional
      Escherichia coli repressor of biotin biosynthesis.
AB  - The Escherichia coli repressor of biotin biosynthesis (BirA) is a unique
      transcriptional repressor which catalyzes synthesis of its own corepressor and
      catalyzes attachment of a cofactor to an essential metabolic enzyme. BirA both
      catalyzes synthesis of biotinyl-5'-AMP from the substrates ATP and biotin and
      transfer of the biotin moiety from the adenylate to a lysine residue of a subunit
      of the acetyl-CoA carboxylase. BirA-bio-5'-AMP, moreover, binds sequence
      specifically to the biotin operator to repress transcription of the biotin
      biosynthetic genes. Using a combination of kinetic measurements of binding of the
      two ligands, biotin and bio-5'-AMP, to BirA as well as proteolytic digestion
      experiments, we have found evidence for at least three discrete conformational
      states of BirA. Results of stopped-flow fluorescence measurements of association
      of both ligands with BirA indicate that the process involves initial formation of
      a collision complex followed by a slow conformational change. The kinetics of the
      conformational change are distinct for the two ligands and are the basis for the
      difference in the thermodynamic stabilities of the two protein-ligand complexes.
      Different rates of proteolytic digestion of apoBirA and complexes of BirA with
      the two ligands were also observed. Results of the combined approaches indicate
      that apoBirA, and the BirA-bio-5'-AMP and BirA-biotin complexes are
      conformationally distinct.

PMID- 8527436
TI  - Structure of a new crystal form of a DNA dodecamer containing T.(O6Me)G base
      pairs.
AB  - The structure of the synthetic dodecamer (d[CGTGAATTC(O6Me)GCG])2 has been
      determined to a resolution of 2.25 A and refined to a final R factor of 16.7%.
      The volume of the unit cell is significantly smaller by 16% than the original
      Drew and Dickerson parent dodecamer [Drew, H. R., Wing, R. M., Takano, T., Broka,
      C., Tanaka, S., Itakura, K., & Dickerson, R. E. (1981) Proc. Natl. Acad. Sci.
      U.S.A. 78, 7318-7322]. The double helix is in a different position in the unit
      cell, rotated by -85.9 degrees, and translated by 9.9 A around the helical axis
      with respect to the parent structure. The intermolecular arrangement of helices,
      characterized by double hydrogen bonded guanine-guanine minor groove
      interactions, remains conserved. The molecular geometry exhibits several
      significant changes that are related to the changed position of the helix and the
      presence of two mismatched base pairs with O6-methylguanine. Both mispairs are
      found in a symmetrical T(anti).(O6Me)G(anti) conformation, and the methyl groups
      are in proximal orientation. The hydration pattern of the structure is different
      and can be related to changes in the minor groove geometry. An incorrect model
      that was isomorphous to the parent dodecamer could be refined to a low R factor.
      Characteristics of the refinement and of the geometry that are indicative of
      incorrect structures have been analyzed.

PMID- 8527437
TI  - Solution conformation of [AF]dG opposite a -2 deletion site in a DNA duplex:
      intercalation of the covalently attached aminofluorene ring into the helix with
      base displacement of the C8-modified syn guanine and adjacent unpaired 3'-adenine
      into the major groove.
AB  - This paper reports the solution conformation of the covalent aminofluorene-C8
      deoxyguanosine [AF]dG adduct positioned opposite a -2 deletion site in a DNA
      oligomer duplex. The combined NMR and molecular mechanics computational studies
      were undertaken on the [AF]dG adduct embedded in the d(C5-[AF]G6-A7-C8).d(G17
      G18) sequence context in a duplex containing 12 residues on the modified strand
      and 10 on the partner strand, with no bases opposite the [AF]dG6-dA7 segment. The
      exchangeable and nonexchangeable protons of the aminofluorene moiety and the
      nucleic acid were assigned following analysis of two-dimensional NMR data sets in
      H2O and D2O solution. The solution conformation of the [AF]dG.2del 12-mer duplex
      has been determined by incorporating intramolecular and intermolecular proton
      proton distances defined by upper and lower bounds deduced from NOESY spectra as
      restraints in molecular mechanics computations in torsion angle space. The
      aminofluorene ring of [AF]dG6 is intercalated between intact Waston-Crick
      dC5.dG18 and dC8.dG17 base pairs with the deoxyguanosine base of [AF]dG6 in a syn
      alignment displaced into the major groove. The syn glycosidic torsion angle at
      [AF]dG6 is supported by both carbon and proton chemical shift data for the sugar
      resonances of the modified deoxyguanosine residue. The unpaired dA7 base is also
      looped out of the helix into the major groove with the purine rings of [AF]dG6
      and dA7 stacking on each other in the groove. The long axis of the intercalated
      aminofluorene ring is parallel to the long axis of the flanking dG.dC base pairs.
      The intercalation site is wedge shaped with a pronounced propeller-twisting and
      buckling of the dC5.dG18 base pair. The deoxyguanosine base of [AF]dG6, which is
      positioned in the major groove, is inclined relative to the helix axis and stacks
      over the 5'-flanking dC5 residue in the solution structure. The intercalative
      base displacement structure of the [AF]dG.2del 12-mer duplex exhibits several
      unusually shifted proton resonances that can be readily accounted for by the ring
      current contributions of the deoxyguanosine purine and carcinogen fluorene
      aromatic rings of the [AF]dG6 adduct. We note similarities between the present
      conformation of [AF]dG positioned opposite a -2 deletion site with our earlier
      conformational studies of [AF]dG positioned opposite a -1 deletion site [Mao, B.,
      Cosman, M., Hingerty, B. E., Broyde, S., & Patel, D. J. (1995) Biochemistry 34,
      6226-6238]. For both conformations, the aminofluorene carcinogen inserts into the
      helix at the deletion site through base displacement of the modified
      deoxyguanosine in a syn alignment into the major groove and directed toward its
      5'-neighbor in the sequence. These structures provide a molecular explanation of
      how transient strand slippage of the lesion-containing segment can be
      accommodated by a double helix following translesion synthesis.

PMID- 8527438
TI  - Structure of a dicationic monoimidazole lexitropsin bound to DNA.
AB  - An X-ray crystal structure has been solved of the complex of a dicationic
      lexitropsin with a B-DNA duplex of sequence CGCGAATTCGCG. The lexitropsin is
      identical to netropsin except for replacement of the first methylpyrrole ring by
      methylimidazole, converting a =CH- to =N-. Crystals are isomorphous with those of
      the DNA dodecamer in the absence of drug. Although the =N- for =CH- substitution
      was intended to make that locus on the drug molecule compatible with a G.C base
      pair, electrostatic attraction for the two cationic ends of the drug
      predominates, and this lexitropsin binds to the same central AATT site as does
      the parent netropsin. But unlike netropsin, this lexitropsin exhibits end-for-end
      disorder in the crystal. Both orientations were refined separately to completion.
      Final residual errors at 2.25 A resolution for the 2358 reflections above 2 sigma
      in F are R = 0.165 for one orientation (LexA) with 37 water molecules and 0.164
      for the inverted drug orientation (LexB) with 40 water molecules. This molecular
      disorder is probably attributable to a weakening of binding to the AATT site
      occasioned by the imidazole-for-pyrrole substitution.

PMID- 8527439
TI  - A novel endoprotease responsible for the specific cleavage of transducin gamma
      subunit.
AB  - Isoprenylated/methylated heterotrimeric G proteins play important roles in a
      large number of signal transduction processes. While the enzymology of
      isoprenylated/methylated protein biosynthesis is well understood, nothing is
      known about how these proteins are degraded. In this article, a novel
      endoproteolytic activity has been identified from bovine retina and is shown
      specifically to remove the glycylfarnesylcysteine moiety from the carboxyl
      terminus of T gamma. When tested in a GTP binding assay, freshly prepared
      proteolyzed T beta gamma was unable to catalyze the binding of guanosine 5'
      (gamma-thio)triphosphate (GTP-gamma-S) to T alpha in the presence of detergent
      solubilized rhodopsin. The optimum pH for this proteolytic activity is
      approximately 6, and the pH profile corresponds to an enzyme having pKa's of 4.4
      +/- 0.1 and 7.7 +/- 0.1 for its active site residues. After analyzing a series of
      protease inhibitors, we found E-64, a specific thiol protease inhibitor, to be
      the most effective irreversible inhibitor of this enzyme, suggesting that the
      endoprotease might be a thiol protease. Affinity labeling studies using
      biotinylated affinity labeling probes have identified a 35 kDa protein as a
      candidate for the endoprotease.

PMID- 8527440
TI  - Physical behavior of the hydrophobic core of membranes: properties of 1-stearoyl
      2-linoleoyl-sn-glycerol.
AB  - Phospholipids containing a saturated fatty acid in the primary position and an
      unsaturated fatty acid in the secondary position are a major structural part of
      biological membranes. The mixed-chain hydrophobic core of the membranes is the
      diacylglycerol part. To better understand the core properties of membranes we
      have studied the physical behavior of 1-stearoyl-2-linoleoyl-sn-glycerol (SLDG)
      by X-ray diffraction and differential scanning calorimetry (DSC) in the dry and
      hydrated states. Dry SLDG has four polymorphic phases: alpha (transition
      temperature, 11.6 degrees C; delta H = 7.5 kcal/mol); sub-alpha 1 (3.0 degrees C;
      0.6 kcal/mol); sub-alpha 2(-1.0 degrees C; 0.5 kcal/mol); and beta' (16.1 degrees
      C; 15.4 kcal/mol). The alpha, sub-alpha 1, and sub-alpha 2 phases are metastable
      with a probable extended bilayer structure (d001 approximately 59.5 A). The chain
      packing of the alpha phase is hexagonal, while sub-alpha 1 and sub-alpha 2 have
      pseudohexagonal chain packing. The beta' phase has a tilted bilayer structure
      (46.9 A) with strong wide-angle diffractions, suggesting elements of orthorhombic
      perpendicular packing. Compared to saturated 1,2-diacylglycerols, SLDG packs much
      less efficiently, but, when compared to 1-stearoyl-2-oleoyl-sn-glycerol, it
      appears to pack somewhat more efficiently. Thus polyunsaturated linoleate chains
      appear to pack marginally more effectively with the saturated stearate chains
      than do monounsaturated chains. SLDG hydrates with 0.5 mol of H2O, which prevents
      the beta' phase from forming. Only one hydrated alpha phase (alpha w) and two
      hydrated sub-alpha (sub-alpha w1, sub-alpha w2) phases are formed. These phases
      are similar in structure to the nonhydrated alpha phases, but the bilayer period
      is increased by about 2 A (d001 approximately 61.5 A). This causes minor changes
      in polymorphism, including lower melting temperatures and enthalpy. A comparison
      of diacylglycerols to phosphatidylcholines with the same chains shows that the
      addition of a strong polar group (e.g., phosphocholine) to the free hydroxyl of
      the glycerol depresses chain melting and prevents the more efficient packing of
      the SLDG core of the bilayer.

PMID- 8527441
TI  - Lipoxin A4 receptor activation is distinct from that of the formyl peptide
      receptor in myeloid cells: inhibition of CD11/18 expression by lipoxin A4-lipoxin
      A4 receptor interaction.
AB  - Lipoxin A4 (LXA4) interacts with high-affinity receptors in human neutrophils and
      differentiated HL-60 cells. Recently, we characterized a myeloid-derived cDNA
      that encodes a LXA4 high-affinity receptor (LXA4R) [Fiore, S., Maddox, J. F.,
      Perez, H. D., and Serhan, C. N. (1994) J. Exp. Med. 180, 253-260] denoted earlier
      as a related N-formyl peptide receptor (RFP). To examine the selectivity of this
      receptor we tested its preference for specific binding of 3H-LXA4 versus 3H-N
      formylmethionyl-leucyl-phenylalanine (3H-FMLP). When receptor-transfected Chinese
      hamster ovary cells were exposed to either 3H-LXA4 or 3H-FMLP, the receptor
      affinity for LXA4 exceeded by 1000-fold that of FMLP (6.1 nM vs 5 microM). Upon
      differentiation, HL-60 cells acquire high-affinity binding sites and respond to
      both LXA4 and FMLP. Northern blot analysis of differentiated HL-60 cells using an
      RFP probe showed a characteristic band at 2.1 kb. Differentiated HL-60 cells
      exposed to an RFP antisense oligonucleotide selectively lost 3H-LXA4 binding as
      well as LXA4-stimulated lipid remodeling that paralleled the loss of mRNA for
      LXA4R. In contrast, the specific mRNA for the FMLP receptor, 3H-FMLP specific
      binding, and FMLP-induced phospholipase D activity were still observed. Treatment
      of human neutrophils with antisera raised against a peptide in the LXA4R third
      extracellular domain also resulted in selective abrogation of 3H-LXA4 specific
      binding with polymorphonuclear leukocytes (PMN) without blocking 3H-FMLP binding.
      FMLP-stimulated CD11b upregulation as well as homotypic aggregation of PMN was
      inhibited by LXA4 (which at 10(-9) M gave approximately 1 log unit shift to the
      right in the FMLP dose-response curve). The addition of LXA4R antisera did not
      alter FMLP-induced responses in PMN but completely blocked LXA4 actions. These
      results indicate that altering the expression of the LXA4R protein by blockage of
      transcriptional mechanisms or hindrance of the LXA4R extracellular domains leads
      to loss of LXA4 specific binding and blockage of LXA4 signaling. Moreover, they
      indicate that in myeloid cells LXA4-LXA4R interactions are dissociable from those
      of FMLP and that LXA4 regulates CD11/18 on the PMN surface.

PMID- 8527442
TI  - Yeast protein farnesyltransferase: steady-state kinetic studies of substrate
      binding.
AB  - Protein farnesyltransferase (PFTase) catalyzes the alkylation of cysteine in C
      terminal CaaX sequences of a variety of proteins, including Ras, nuclear lamins,
      large G-proteins, and phosphodiesterases, by farnesyl diphosphate (FPP). These
      modifications enhance the ability of the proteins to associate with membranes and
      are essential for their respective functions. The binding mechanism for yeast
      PFTase was deduced from a combination of steady-state kinetic and equilibrium
      studies. Rates for prenylation were measured by a continuous assay based on an
      enhancement in the fluorescence of the dansyl moiety in pentapeptide dansyl-GCVIA
      upon farnesylation by FPP. Unreactive substrate analogs for FPP and dansyl-GCVIA
      gave steady-state inhibition patterns for the dead-end inhibitors typical of an
      ordered sequential mechanism in which FPP adds to the enzyme before the peptide.
      The kinetic analysis was complicated by substrate inhibition for dansyl-GCVIA.
      The substrate inhibition was reversed at high concentrations of FPP, indicating
      that formation of the nonproductive enzyme--peptide complex is competitive with
      respect to FPP. Progress curves were fitted to an integrated form of the rate
      expression to determine the catalytic constant, kcat = 4.5 +/- 1.9 s-1, and the
      Michaelis constant for dansyl-GCVIA, KMD = 0.9 +/- 0.1 microM. The dissociation
      constant for FPP, KD = 75 +/- 15 nM, was measured using a membrane retention
      assay.

PMID- 8527443
TI  - Effect of metal-ligand mutations on phosphoryl transfer reactions catalyzed by
      Escherichia coli glutamine synthetase.
AB  - Glutamine synthetase (GS) converts glutamate to glutamine in the presence of ATP
      and ammonia and requires two divalent metal ions, designated n1 and n2, for
      catalysis. The first intermediate, gamma-glutamyl phosphate, is formed during
      catalysis by the transfer of the gamma-phosphate of ATP to the gamma-carboxylate
      of glutamate. Efficient phosphoryl transfer between these two negatively charged
      moieties is thought to be mediated by the n2 metal. To explore the role of the n2
      metal in catalysis, histidine 269, a ligand to the n2 metal, was changed to
      aspartate, asparagine, glutamate, and glutamine by site-directed mutagenesis. All
      of the mutants bind two manganese ions as determined by EPR titration. The
      mutations had little effect on the substrate Km's except in the case of H269E
      which exhibited a Km Glu = 92 mM, a 1000-fold increase compared to that for WT
      (Km Glu = 70 microM). The ability of these mutants to catalyze phosphoryl
      transfer to glutamate or to the inhibitor phosphinothricin was examined by rapid
      quench kinetic experiments. Phosphorylated phosphinothricin was detected by 31P
      NMR and shown to be produced by both mutants and WT. The rate of phosphoryl
      transfer to PPT for H269E is reduced 100-fold (0.030 s-1) compared to WT (8 s-1).
      The extra negative charge around the n2 metal ion contributed by glutamate 269
      severely reduces the ability of the n2 metal to mediate efficient glutamate
      binding in the presence of negatively charged ATP and weakens the interactions
      between metal ion and the reactants in the transition state, thus resulting in a
      lower rate of phosphoryl transfer.

PMID- 8527444
TI  - Discovery of a third coenzyme in sarcosine oxidase.
AB  - Denaturation of recombinant sarcosine oxidase or the natural enzyme isolated from
      Corynebacterium sp. P-1 with guanidine hydrochloride releases noncovalently bound
      FAD and a second UV-absorbing component (peak 2) which comigrates with NAD+
      during reversed-phase HPLC. Both FAD and peak 2 are also found in extracts
      prepared by incubating sarcosine oxidase at 37 degrees C for 30 min, a procedure
      which causes partial (approximately 50%) release of the enzyme's noncovalently
      bound FAD. Peak 2 in the 37 degrees C extract is heat labile and decomposes upon
      boiling for 5 min at pH 8.0. A similar instability was observed with NAD+.
      Reaction of the 37 degrees C extract from sarcosine oxidase with
      phosphodiesterase yields nicotinamide mononucleotide, AMP, and FMN, as expected
      for a mixture containing NAD+ and FAD. Peak 2 was converted to NADH upon reaction
      of the 37 degrees C extract with yeast alcohol dehydrogenase in the presence of
      ethanol. Guanidine hydrochloride extracts, prepared from recombinant or natural
      enzyme, contain 1 mol of NAD+/mol of FAD. Since sarcosine oxidase contains 1 mol
      of noncovalently bound FAD, the results show that the enzyme also contains 1 mol
      of NAD+. The NAD+ is tightly bound and is not lost during enzyme purification. It
      is not susceptible toward hydrolysis by NADase, reduction by alcohol
      dehydrogenase, or nucleophilic attack by cyanide. Unlike the flavins in sarcosine
      oxidase, NAD+ is not reduced by sarcosine and is not in redox equilibrium with
      the flavins.

PMID- 8527445
TI  - Magnesium acetate induces a conformational change in Escherichia coli primase.
AB  - Primase from Escherichia coli is a single-stranded DNA-dependent RNA polymerase.
      As such, it requires magnesium to carry out catalysis. Limited tryptic digestion
      was used to probe the conformations of primase as a function of magnesium acetate
      concentration. In the absence of magnesium, trypsin cleaved primase at three
      sites. Magnesium acetate induced a conformational change such that one of these
      sites became inaccessible to trypsin digestion and a new site became trypsin
      accessible. The conformational change was only induced by Mg(OAc)2 and not MnCl2,
      CaCl2, NaOAc or LiCl, indicating a clear magnesium acetate-dependent
      conformational change. The effect was slightly induced by MgSO4 and MgCl2. An
      allosteric binding model indicates that primase binds at least two magnesiums in
      a cooperative manner. The data were best fit to a two-state model in which one
      conformation had a high affinity for magnesium, KR = 83.4 M-1, and the other
      state had virtually no affinity.

PMID- 8527446
TI  - Specific cleavage of a DNA triple helix by FeII.bleomycin.
AB  - The specific cleavage of a DNA triple helix by FeII.bleomycin (BLM) is
      demonstrated. Triplex-specific cleavage was observed on both strands of the 32
      base pair (bp) duplex at the duplex-triplex junctions. Strand scission products
      and alkali labile lesions were both formed. The strongest BLM cleavage site was
      located at the 5'-duplex-triplex junction, which is also the preferred triplex
      binding site of intercalating agents [Collier, D. A., Mergny, J.-L., Thuong, N.
      T., & Helene, C. (1991) Nucleic Acids Res. 19, 4219-4224]. The preference of BLM
      for the 5'-junction does not appear to derive from selective intercalative
      binding at this site. This is supported by the observation that phleomycin, which
      contains a thiazolinylthiazole moiety rather than a planar bithiazole ring
      system, exhibited the same selectivity of triplex cleavage as BLM. Cleavage of
      the triple helix by FeII.BLM was unaffected by concentrations of Mg2+ up to 5 mM,
      suggesting possible therapeutic applications of this novel DNA target. Molecular
      modeling calculations of the triplex region suggested that dramatic variations in
      minor groove width and depth occur at the duplex-triplex junctions, particularly
      at the 5'-junction. Moreover, the minor groove at these sites was calculated to
      be somewhat shallower and wider than the minor groove of B-DNA. These results
      suggest that the preference of BLM for the duplex-triplex junctions derives from
      selective recognition of minor groove shape at these sites and thus reflects
      conformation-selective, rather than sequence-selective, DNA recognition by
      FeII.BLM.

PMID- 8527447
TI  - Involvement of cysteine 289 in the catalytic activity of an NADP(+)-specific
      fatty aldehyde dehydrogenase from Vibrio harveyi.
AB  - Fatty aldehyde dehydrogenase (Vh.ALDH) from the luminescent bacterium, Vibrio
      harveyi, may be implicated in controlling luminescence as it catalyzes the
      oxidation of the fatty aldehyde substrate for the light-emitting reaction. On the
      basis of the amino-terminal sequence of Vh.ALDH, a degenerate probe was used to
      screen a genomic library of V harveyi in pBR322, a positive clone was selected
      containing the Vh.ALDH gene and expressed in Escherichia coli, and the enzyme was
      purified to homogeneity. Although the sequence of the V. harveyi ALDH
      significantly diverged from other aldehyde dehydrogenases, mutation of a
      conserved cysteine implicated in catalysis completely inactivated the enzyme
      without loss of its ability to bind nucleotides, consistent with a catalytic role
      for this residue. Using absorption and fluorescence assays for NAD(P)H, it was
      shown that NAD+ and NADP+ bound to the same site and that saturation of Vh.ALDH
      with NADP+ occurred with a Michaelis constant (Km = 1.4 microM) over 40 times
      lower than that reported for other aldehyde dehydrogenases. Although V. harveyi
      aldehyde dehydrogenase is unique in terms of its high specificity for NADP+, the
      identification of a catalytic conserved cysteine in Vh.ALDH clearly indicates
      that a highly related mechanism and structure have been retained among even the
      most diverged aldehyde dehydrogenases.

PMID- 8527448
TI  - Frequency spectrum of NH bonds in eglin c from spectral density mapping at
      multiple fields.
AB  - The internal mobility of the protein eglin c is characterized with spectral
      density functions of the NH vectors obtained from heteronuclear NMR relaxation at
      multiple field strengths (7.04, 11.74, and 14.1 T). The spectral density
      functions, J(omega), describe the frequency spectrum of the rotational
      fluctuations of the XH bond vectors (15N-1H and 13C-1H). The spectral density
      mapping approach [Peng, J. W., & Wagner, G. (1992a) J. Magn. Reson. 98, 308-332;
      Peng, J. W., & Wagner, G (1992b) Biochemistry 31, 8571-8586] permits the direct
      evaluation of J(omega) at the five frequencies 0, omega N, magnitude of omega H -
      magnitude of omega X, omega H, and magnitude of omega H + magnitude of omega X.
      The 15N-1H relaxation measurements from three field strengths on 15N-enriched
      eglin c resulted in 18 relaxation rate constants per NH bond and 13 unique
      evaluations of each NH spectral density function. Dynamic heterogeneity along the
      protein backbone is manifested most clearly in spectral density values at lower
      frequencies (< 100 MHz). The effective value of J(0), J(eff)(0), is the most
      sensitive probe of dynamics as it is affected by both rapid internal motions and
      slow chemical exchange processes. Low J(eff)(0) and J(omega N) values are
      correlated with fast amide proton-deuteron exchange rates; the converse, however,
      is not observed. Anomalies in J(omega H) and J(magnitude of omega H +/- magnitude
      of omega N) observed in the first applications of the spectral-mapping approach
      are now attributable to the high sensitivity of these values to small errors in
      the rate constants. These anomalies can be reduced by the use of a reduced
      spectral-mapping procedure. The use of multiple field strengths allows the
      identification of slow exchange processes manifested as an increase of J(eff)(0)
      with spectrometer field strength.

PMID- 8527449
TI  - Stoichiometry of p22-phox and gp91-phox in phagocyte cytochrome b558.
AB  - The phagocyte NADPH oxidase complex is an unusual electron transfer system. Its
      principal component, cytochrome b558, is a heme-containing integral membrane
      protein consisting of two subunits, gp91-phox and p22-phox. We used a novel
      method to measure precisely the gp91-phox:p22-phox stoichiometry. Cytochrome b558
      was isolated in high purity from human neutrophil membrane preparations using a
      novel affinity purification method. We performed direct peptide sequencing of
      purified cytochrome b558 and detected two amino acid sequences which matched
      predicted sequences for gp91-phox and p22-phox. We quantitated amounts of both
      amino acids released from p22-phox and gp91-phox in each sequencing cycle.
      Averaging over 25 cycles, the mean p22-phox:gp91-phox ratio of released amino
      acids was 0.93 +/- 0.01. To correct for recovery differences between individual
      amino acids, we measured individual p22-phox:gp91-phox ratios for the eight
      different amino acids common to both p22-phox and gp91-phox in the first 25
      positions. The mean of individual p22-phox:gp91-phox ratios for the eight common
      amino acids was 0.96 +/- 0.05. The p22-phox:gp91-phox ratios for each of the
      eight common amino acids varied from 0.81 to 1.20. Taken together, measured
      ratios for total and individual amino acids are consistent with a predicted ratio
      of 1.0 for 1:1 p22-phox:gp91-phox stoichiometry in cytochrome b558.

PMID- 8527450
TI  - Structural changes in the lumirhodopsin-to-metarhodopsin I conversion of air
      dried bovine rhodopsin.
AB  - Structural changes during the photochemical reactions of unhydrated air-dried
      films of bovine rhodopsin in rod outer segments were examined by visible and
      Fourier transform infrared (FTIR) spectroscopy at 200, 240, and 280 K. These
      films exhibited conversion from a lumirhodopsin state to a metarhodopsin I state
      with a time constant of 13.5 min at 280 K, but did not form metarhodopsin II at
      all, as observed earlier for digitonin-extracted rhodopsin in dry gelatin films
      [Wald, Durell, and St. George (1950) Science 111, 179-181]. Lumirhodopsin which
      was stable in the dry film was very similar to normal lumirhodopsin. The
      metarhodopsin I-like state retained properties characteristic of lumirhodopsin in
      regard to a twisted structure between the C14-H and the Schiff base of the
      chromophore, and perturbation around Glu122, although the C-C stretch frequencies
      of the chromophore were identical with those of metarhodopsin I. Thus, under dry
      conditions some of the structural changes that lead to metarhodopsin I are
      partially inhibited. These defects could result in stable lumirhodopsin and the
      failure to form metarhodopsin II, which is in equilibrium with metarhodopsin I.

PMID- 8527451
TI  - Membrane thinning caused by magainin 2.
AB  - Magainin 2 is a 23-residue antibiotic peptide found in the skin of Xeonpus laevis
      (African clawed frog). It belongs to a broad class of alpha-helical peptides
      which interact directly with the lipid bilayer. Very little is presently known
      about the nature of this peptide/lipid interaction on the molecular level. We
      have performed a sequence of lamellar X-ray diffraction experiments to provide
      some insight into the nature of this interaction. We have found that, at
      concentrations below the critical concentration for lysis, the peptide causes the
      membrane thickness to decrease roughly in proportion to the peptide
      concentration. We further show that this thinning is consistent with a model
      where the peptide adsorbs within the headgroup region of the lipid bilayer at
      these concentrations. The energy cost of this thinning may also explain why the
      peptide inserts at high concentrations. We have already shown that a similar
      interaction exists for alamethicin interacting with
      diphytanoylphosphatidylcholine, and it should hold for a wide variety of
      peptide/lipid systems.

PMID- 8527452
TI  - Characterization of the active site cysteine residues of the thioredoxin-like
      domains of protein disulfide isomerase.
AB  - The dithiol/disulfide active sites of each of the two isolated thioredoxin-like
      domains of protein disulfide isomerase (PDI) expressed in Escherichia coli have
      been characterized in order to understand their catalytic mechanisms and their
      functions in PDI. In each of the folded domains, as in other proteins of the
      thioredoxin family, only one of the cysteine residues of the active site sequence
      -Cys-Gly-His-Cys- is accessible, and its thiol group is highly reactive and has a
      low pKa value. The kinetics and equilibria have been measured of the reactions
      between the active site cysteine residues and glutathione, the predominant
      thiol/disulfide reagent of the endoplasmic reticulum. A disulfide bond can be
      formed very rapidly between the pair of cysteine residues of each domain, but
      each disulfide bond is very unstable and reacts rapidly with reduced glutathione.
      The very low stabilities of these disulfide bonds, which destabilize the protein
      structures, account for the efficiency with which PDI and each of the isolated
      domains can introduce disulfide bonds into proteins. These kinetics and
      equilibrium data go far in helping to understand the catalytic mechanism of PDI
      and its individual domains.

PMID- 8527453
TI  - Probing the role of electrostatic forces in the interaction of Clostridium
      pasteurianum ferredoxin with its redox partners.
AB  - The ability of several low-potential redox proteins to mediate electron transfer
      between Clostridium pasteurianum pyruvate-ferredoxin oxidoreductase and
      hydrogenase has been evaluated in a coupled enzymatic assay. The active electron
      mediators, whatever their structure, must have a reduction potential compatible
      with the two enzymes, but for proteins of similar potentials, a marked
      specificity is displayed by 2[4Fe-4S] ferredoxins of the clostridial type. Such
      ferredoxins are small proteins exchanging electrons with many enzymes involved in
      the metabolism of anaerobic bacteria. The forces underlying the interactions of
      ferredoxin with hydrogenase and pyruvate-ferredoxin oxidoreductase have been
      examined with an emphasis on electrostatics: site-directed mutagenesis
      experiments have been used to individually convert all conserved glutamates and
      aspartates of C. pasteurianum ferredoxin into either neutral or positively
      charged amino acids. Also, up to four of these residues have been replaced
      simultaneously. The biological activities of the resulting variants depend very
      little on the number and the distribution of the anionic side chains on the
      surface of the ferredoxin. Only those molecular forms for which the immediate
      environment of the clusters is perturbed, independently of the charge
      distribution, display variations in their catalytic properties. It is concluded
      that electron transfer between C. pasteurianum 2[4Fe-4S] ferredoxin and its
      partners is far less dependent on electrostatic interactions than in many other
      well-documented electron transfer systems.

PMID- 8527454
TI  - Investigation of the structural requirements of the troponin C central helix for
      function.
AB  - The two globular Ca(2+)-binding domains of troponin C are connected by a three
      turn, exposed central helix. The requirements of this helical linker for
      regulatory function are not fully understood. In the present work we investigated
      the structural requirement of the linker using a series of insertion mutations
      that differ in predicted flexibility. TnCinrc has a nine-residue flexible random
      coil insert, TnCinpp has a nine-residue rigid polyproline insert (three turns),
      and TnCin alpha h has a seven-residue insert with high potential of forming alpha
      helix. TnCinrc and TnCinpp were defective in the activation of the regulated
      actomyosin ATPase activity in the presence of Ca2+ when compared to wild type or
      TnCin alpha h, suggesting that altering the flexibility of the central helix
      impairs the regulatory function of troponin C. TnCin alpha h, TnCinrc, and
      TnCinpp had 87% +/- 3, 62% +/- 3, and 58% +/- 2 of the wild type activity,
      respectively (n = 6). All insertions in the central helix resulted in elongation
      of molecule compared to wild type TnC as determined by Stokes' radius. The Ca(2+)
      affinity, the Ca(2+)-dependence of the actomyosin ATPase, and the stability of
      the insertion mutants were similar to wild type. Deletions of up to two turns of
      the central helix have little effect on troponin C function [Dobrowolski, Z., Xu,
      G-Q., & Hitchcock-DeGregori, S. E. (1991) J. Biol. Chem. 266, 5703-5710]. In
      another mutant (TnCd11) the entire central helix, 87KEDAKGKSEEE97, was deleted.
      With TnCd11, activation of the actomyosin ATPase activity in the presence of Ca2+
      was normal, but inhibition in the absence of Ca2+ was less effective. Interaction
      of TnCd11 with TnI was altered. There was a 2-fold excess of TnCd11 in
      reconstituted Tn complex, consistent with another report [Babu, A., Rao, V. G,
      Su, H., & Gulati, J. (1993) J. Biol. Chem. 268, 19232-19238]. Our results suggest
      that the native length and structure of the central helix are optimal for normal
      regulatory function and that connectivity alone is insufficient for TnC function.

PMID- 8527455
TI  - The stability of tropomyosin, a two-stranded coiled-coil protein, is primarily a
      function of the hydrophobicity of residues at the helix-helix interface.
AB  - The sequences of coiled coils are characterized by a repeating heptad of amino
      acids, abcdefg, in which the a and d residues are generally hydrophobic and form
      the interface between the two alpha-helices. In this study, rat and chicken alpha
      tropomyosins (alpha-TMs) have been used as models to determine whether the
      effects of mutations on the stability of two-stranded coiled coils can be
      predicted by a simple algorithm. The thermal stabilities of three wild-type
      muscle alpha-TMs and nine chimeras, in which the second and/or sixth or ninth
      coding exons of one alpha-TM cDNA were replaced with exons from other alpha-TM
      cDNAs, with a sequence encoding the GCN4 leucine zipper or a random coil
      sequence, have been obtained using circular dichroism spectroscopy. Tropomyosin
      is almost completely helical along its entire length, but there is no correlation
      of the thermal stability of the alpha-TMs with the helical propensity of their
      component amino acids. The stability can be predicted (P = 0.90), however, by
      assigning a weight to every amino acid residue in each sequence, depending on its
      frequency of occurrence at the abcdef or g position in a data base of coiled-coil
      fibrous proteins, and summing all the weights. The correlation improves if only
      the residues at the a and d interface are counted (P = 0.94). The major factor
      modulating the thermal stability appears to be the hydrophobicity of the residues
      at the coiled-coil interface, since there is a high correlation (P = 0.91) of the
      TM values with the sum of the hydrophobic moments of the residues found at the a
      and d positions.

PMID- 8527456
TI  - Fluorescent styryl dyes as probes for Na,K-ATPase reaction mechanism:
      significance of the charge of the hydrophilic moiety of RH dyes.
AB  - The fluorescence responses of a series of potential-sensitive styryl-based dyes
      (either zwitterionic RH160, RH421, di-4-ANEPPS, or positively charged RH795,
      RH414, RH461) to phosphorylation of Na,K-ATPase from ATP or inorganic phosphate,
      and ouabain binding to phospho- or dephosphoforms, have been characterized and
      compared in broken membrane preparations of the enzyme. Zwitterionic dyes were
      more sensitive to molecular events in the Na,K-ATPase reaction cycle than
      positively charged dyes, but the net charge did not affect the sensitivity of the
      dyes to a transmembrane electric field. The major part of the response of the
      zwitterionic dyes to formation of phosphoenzymes was due to a change in the
      quantum yield of fluorescence. Computer modeling of dyes with identical
      chromophore structure, and experimental characterization of their optical
      properties in bulk solvents, revealed two general trends: (1) the absorption
      maximum of the zwitterionic dye was blue-shifted with respect to the positively
      charged dye; (2) the quantum yield of the zwitterionic dye was higher and the
      fluorescence lifetime was longer than that for the positively charged dye.
      Spectral properties of the dyes in the membrane depended on the presence of Na,K
      ATPase. We suggest, that (1) electrostatic interactions between the enzyme and
      the hydrophilic headgroup of the dye by changing the charge of hydrophilic moiety
      and thus modifying the net charge of the dye molecule cause both the spectral
      shifts and the changes in the quantum yield, and (2) interactions between the
      styryl dyes and the Na,K-ATPase depend on the conformational state of the enzyme.

PMID- 8527457
TI  - Inhibition of smooth muscle actomyosin ATPase by caldesmon is associated with
      caldesmon-induced conformational changes in tropomyosin bound to actin.
AB  - The smooth muscle tropomyosin isoforms beta and gamma were isolated in pure form
      and labeled with N-(1-pyrenyl)iodoacetamide (PIA) on the cysteine residues at
      either the N- or the C-terminal region (Cys-36 and Cys-190 of beta- and gamma
      isoforms, respectively). The effect of caldesmon (CaD) on local conformational
      changes in different regions of the tropomyosin molecule was determined on the
      basis of changes in the excimer fluorescence (excited dimer of pyrene) formed in
      homodimers of tropomyosin isoforms. In the absence of actin, excimer fluorescence
      from the pyrene at Cys-190 of gamma-tropomyosin homodimer decreased in a simple
      manner on the addition of CaD, whereas the excimer from the Cys-36 of beta
      tropomyosin homodimer exhibited a biphasic change, suggesting that additional
      weak binding sites exist near Cys-36. In the presence of actin, CaD-induced
      changes in the excimer fluorescence of pyrene-tropomyosin were observed only with
      Cys-36, and this change was associated with an inhibition of actin-activated
      myosin ATPase. A competition study with unlabeled tropomyosin isoforms indicated
      that the different excimer changes exhibited by beta- and gamma-tropomyosin in
      the presence of CaD were due to conformational changes in different regions of
      the tropomyosin molecule and not to differences in their affinities for CaD.
      Experiments with recombinant CaD mutants derived using the baculovirus expression
      system showed that the inhibition of tropomyosin potentiation of actomyosin
      ATPase by CaD requires the regions between residues 728-756 and 718-727 on the
      CaD molecule, although the latter region was sufficient for direct interaction
      with tropomyosin.

PMID- 8527458
TI  - Differential effects of ethyl 5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4
      b]pyrazin-7-yl carbamate analogs modified at position C2 on tubulin
      polymerization, binding, and conformational changes.
AB  - NSC 613863 (R)-(+) and NSC 613862 (S)-(-) (CI980) are two chiral isomers of ethyl
      5-amino 2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate which
      have potent antitubulin activity. The S-isomer is a more potent antimitotic
      compound than the R-isomer, and the two isomers differ markedly in binding to
      tubulin [Leynadier, D., Peyrot, V., Sarrazin, M., Briand, C., Andreu, J. M.,
      Rener, G. A., & Temple, C., Jr. (1993) Biochemistry 32, 10675-10682]. To
      understand the origin of such differences, we studied the interactions of three R
      and S-isomer structural analogs which differ in C2 (the chiral carbon), i.e.,
      C179, NSC 337238, and NSC 330770. C179 is a methylated dehydrogenated achiral
      compound. It bound to tubulin with an apparent affinity Ka of (2.29 +/- 0.17) x
      10(4) M-1, inhibited tubulin polymerization in vitro at a half-inhibitory
      concentration (IC50) of 100 microM, and presented no GTPase activity. The
      substitution of -CH3 by -H leads to the NSC 337238 compound. It bound to tubulin
      with a higher affinity [Ka = (2.62 +/- 0.35) x 10(5) M-1] and inhibited tubulin
      polymerization at a lower concentration (IC50 = 14 microM). It presented no
      GTPase activity and induced the formation of abnormal polymers at a protein
      critical concentration (Cr) of 2 mg mL-1. NSC 330770, a demethylated hydrogenated
      molecule, interacted strongly with tubulin [Ka = (3.30 +/- 0.56) x 10(6) M
      1].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527459
TI  - Soluble ezrin purified from placenta exists as stable monomers and elongated
      dimers with masked C-terminal ezrin-radixin-moesin association domains.
AB  - Previous work has indicated that ezrin, a membrane-microfilament linking protein,
      exists largely as a monomeric protein in solution. Here we purify from human
      placenta two cytosolic ezrin species that chromatography differently on gel
      filtration, anion, and cation exchange resins. Both species contain only the
      ezrin polypeptide, yet they do not readily interconvert in vitro as determined by
      gel filtration analysis. Determination of the physical properties of the two
      species indicates that one represents the conventional monomer, whereas the other
      represents highly asymmetric dimers. Chemical cross-linking data support this
      conclusion. Purified ezrin monomers normally have a masked C-terminal domain
      (termed a C-ERMAD) that, upon exposure, can associate with an N-terminal domain
      (termed N-ERMAD) of another ezrin molecule. Here we show that purified ezrin
      dimers also have masked C-ERMADs. On the basis of these results, we suggest a
      working model for the molecular organization of ezrin monomers and dimers and
      propose a hypothesis that explains the stable coexistence of ezrin monomers and
      dimers in placenta. Since radixin and moesin, the two other members of the
      closely related ERM protein family, both contain N- and C-ERMADs, the results we
      have documented and models proposed for ezrin are likely to apply to radixin and
      moesin as well.

PMID- 8527460
TI  - Crystallographic and molecular-modeling studies of lipase B from Candida
      antarctica reveal a stereospecificity pocket for secondary alcohols.
AB  - Many lipases are potent catalysts of stereoselective reactions and are therefore
      of interest for use in chemical synthesis. The crystal structures of lipases show
      a large variation in the shapes of their active site environments that may
      explain the large variation in substrate specificity of these enzymes. We have
      determined the three-dimensional structure of Candida antarctica lipase B (CALB)
      cocrystallized with the detergent Tween 80. In another crystal form, the
      structure of the enzyme in complex with a covalently bound phosphonate inhibitor
      has been determined. In both structures, the active site is exposed to the
      external solvent. The potential lid-forming helix alpha 5 in CALB is well-ordered
      in the Tween 80 structure and disordered in the inhibitor complex. The
      tetrahedral intermediates of two chiral substrates have been modeled on the basis
      of available structural and biochemical information. The results of this study
      provide a structural explanation for the high stereoselectivity of CALB toward
      many secondary alcohols.

PMID- 8527461
TI  - Kinetic mechanism of chloramphenicol acetyltransferase: the role of ternary
      complex interconversion in rate determination.
AB  - Chloramphenicol acetyltransferase (CAT) catalyzes the acetyl-CoA-dependent
      acetylation of chloramphenicol (Cm) by a ternary complex mechanism and with a
      random order of addition of substrates. A closer examination of the mechanism of
      the reaction catalyzed by the type III CAT variant (CATIII) has included the
      measurement of the individual rate constants by stopped-flow fluorimetry at 5
      degrees C. Under all conditions employed, product release from the binary
      complexes in both forward and reverse reactions was found to be too slow to
      account for the observed overall rate of turnover for the reaction. Additional,
      faster routes for product release are achieved via the formation of the
      nonproductive ternary complexes (CAT:3-acetyl-Cm:acetyl-CoA and CAT:CoA:Cm). The
      release of 3-acetyl-Cm from the binary complex is 5-fold slower than kcat (135 s
      1 at 5 degrees C), whereas the dissociation rate constants of 3-acetyl-Cm from
      the ternary complexes with CoA and acetyl-CoA are 120 and 200 s-1, respectively.
      Arrhenius plots of dissociation rate constants indicate a slow release of
      products over a broad temperature range. Computer simulations based on the rate
      constants of CATIII applied to a ternary complex mechanism, assuming random order
      of substrate addition and product release, yielded nonlinear initial rates of
      product formation unless both nonproductive ternary complexes were included in
      the model. Simulated steady-state kinetic analyses based on the latter assumption
      yielded kinetic parameters that compared favorably with those determined
      experimentally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527462
TI  - Veratryl alcohol oxidation by lignin peroxidase.
AB  - Lignin peroxidase (LiP) from the white rot fungus Phanerochaete chrysosporium
      catalyzes the H2O2-dependent oxidation of veratryl alcohol (VA), a secondary
      metabolite of the fungus, to veratryl aldehyde (VAD). The oxidation of VA does
      not seem to be simply one-electron oxidation by LiP compound I (LiPI) to its
      cation radical (VA.+) and the second by LiP compound II (LiPII) to VAD. Moreover,
      the rate constant for LiPI reduction by VA (3 x 10(5) M-1 s-1) is certainly
      sufficient, but the rate constant for LiPII reduction by VA (5.0 +/- 0.2 s-1) is
      insufficient to account for the turnover rate of LiP (8 +/- 0.4 s-1) at pH 4.5.
      Oxalate was found to decrease the turnover rate of LiP to 5 s-1, but it had no
      effect on the rate constants for LiP with H2O2 or LiPI and LiPII, the latter
      formed by reduction of LiPI with ferrocyanide, with VA. However, when LiPII was
      formed by reduction of LiPI with VA, an oxalate-sensitive burst phase was
      observed during its reduction with VA. This was explained by the presence of
      LiPII, formed by reduction of LiPI with VA, in two different states, one that
      reacted faster with VA than the other. Activity during the burst was sensitive to
      preincubation of LiPI with VA, decaying with a half-life of 0.54 s, and was
      possibly due to an unstable intermediate complex of VA.+ and LiPII. This was
      supported by an anomalous, oxalate-sensitive, LiPII visible absorption spectrum
      observed during steady state oxidation of VA. The first order rate constant for
      the burst phase was 8.3 +/- 0.2 s-1, fast enough to account for the steady state
      turnover rate of LiP at pH 4.5. Thus, it was concluded that oxalate decreased the
      turnover of LiP by reacting with VA.+ bound to LiPII. The VA.+ concentration
      measured by electron spin resonance spectroscopy (ESR) was 2.2 microM at steady
      state (10 microM LiP, 250 microM H2O2, and 2 mM VA) and increased to 8.9 microM
      when measured after the reaction was acid quenched. Therefore, we assumed the
      presence of two states of VA.+ bound to LiPII, one ESR-active and one ESR-silent.
      The ESR-silent species, which could be detected after acid quenching, would be
      responsible for the burst phase. Both of the VA.+ species disappeared in the
      presence of 5 mM oxalate. The ESR-active species reached a maximum (3.5 microM)
      at 0.5 mM VA under steady state. From these studies, a mechanism for VA oxidation
      by LiP is proposed in which a complex of LiPII and VA.+ reacts with an additional
      molecule of VA, leading to veratryl aldehyde formation.

PMID- 8527463
TI  - Site-directed mutagenesis of putative GTP-binding sites of yeast beta-tubulin:
      evidence that alpha-, beta-, and gamma-tubulins are atypical GTPases.

PMID- 8527465
TI  - Psychomotor disturbances in psychiatric patients as a possible basis for new
      attempts at differential diagnosis and therapy. Part VI. Evaluation of
      psychomotor training programs in schizophrenic patients.
AB  - Parts I-III of this series established signs of disturbed motor performance--the
      "psychotic motor syndrome" (PMS)--in schizophrenic and endogenous depressed
      patients, which was not found in neurotic/reactive depressed nor healthy persons.
      Part IV yielded EEG signs of concomitant brain dysfunction in these patients,
      which were demonstrated by other (SPECT/PET) neuroimaging methods also. In part V
      we engaged in the development of motor-training programs applied both actively
      and mentally, using the PMS as target syndrome in depressed patients. We
      hypothesized that motor training would not only improve disturbed motor
      behaviour, but ameliorate other symptoms of psychopathology additionally, which
      was supported for these patients. Part VI is the final paper of this series
      demonstrating favourable results of our motor-training programs in 96
      schizophrenic inpatients in two separate investigations. A general discussion to
      the whole series attempts to link motor symptoms to neuroimaging findings of
      brain dysfunction during motor challenge and to modern three- and four-factor
      models of schizophrenic symptomatology. A final version of our complete training
      programs will be published as an appendix to this paper along with information
      regarding the abbreviated test battery.

PMID- 8527464
TI  - Depression in old age. Is there a real decrease in prevalence? A review.
AB  - The discrepancy between the constancy or increase of the prevalence of depressive
      symptoms and dysphoria in old age on one hand, and the decrease in the prevalence
      of the DSM-III diagnoses of major depression and dysthymia on the other, is
      discussed in light of the most frequent explanatory hypotheses such as memory
      defects, interpretation of depressive as somatic symptoms, higher risk of
      institutionalization as well as higher mortality of depressives and a mitigated
      course of depression in old age. We conclude that higher mortality, mitigation
      and the rarity of true late-onset depression are arguments for a real decline in
      prevalence, which occurs in accordance with the decline in all psychiatric
      disorders that are connected with emotional upheavals and substance ingestion. On
      the other hand, the connection of depressive states with somatic illness is
      strengthened, and according to preliminary validation studies, clinically
      relevant depressive states not reaching the threshold of DSM-III diagnoses may be
      typical for the depressive psychopathology of old age.

PMID- 8527466
TI  - Frontal lobe degeneration of non-Alzheimer type and Pick's atrophy: lumping or
      splitting?
AB  - We report six cases of presenile (five) and senile (one) progressive dementia
      with a mild-to-marked frontal or frontotemporal atrophy and ventricular dilation
      (Frontal Lobe Degeneration [FLD]). The most prominent microscopic features were
      layer-dependent neuronal depletion of the cortex, spongiosis, and cortical and
      subcortical gliosis. Five cases showed additional degeneration of the S. nigra,
      and two also had motor neuron disease. Despite the absence of Pick cells and
      bodies, such cases have many features in common with Pick atrophy. Because Pick
      cells and bodies are inconstantly occurring features in otherwise typical cases
      of Pick atrophy, they cannot be regarded as inevitable markers of the latter. In
      our opinion, cases with mild frontal or frontotemporal atrophy as described
      herein and by others match the grades 1 and 2 in terms of Schneider's
      classification of Pick atrophy [37]. As long as the etiology of both Pick atrophy
      and the so-called FLD is unknown, and we finally have to follow morphological
      criteria for classification, there is apparently no convincing reason to
      introduce a separate category, such as FLD or FTA, for the cases with moderate or
      mild frontal atrophy and dementia of frontal lobe type, which can be sufficiently
      classified with the Pick spectrum of lobar atrophy.

PMID- 8527467
TI  - Growth hormone response to apomorphine in panic disorder: comparison with major
      depression and normal controls.
AB  - Several lines of evidence suggest that dopamine might be involved in anxiety
      states. In the present study we assessed the growth hormone (GH) response to 0.5
      mg apomorphine (a dopaminergic agonist) in 10 male drug-free inpatients meeting
      Research Diagnostic Criteria for panic disorder who were compared with 10 male
      major depressive inpatients and 10 male normal controls. The three groups
      differed significantly in the GH peak response (mean +/- SD): 27.8 +/- 12.5 ng/ml
      in panics, 5.4 +/- 4.0 ng/ml in major depressives, and 25.8 +/- 11.3 ng/ml in
      normal controls (F(2,27) = 15.3; P = 0.00003). Although there were significant
      differences between panics and major depressives (P = 0.00004), and between major
      depressives and controls (P = 0.00004), panics did not significantly differ from
      controls. These results do not support the hypothesis of an overlap between panic
      and affective disorders, and suggest that the hypothalamo-GH-somatomedin axis
      could be intact in panic disorder.

PMID- 8527468
TI  - Affective modulation of the startle reflex in schizophrenic patients.
AB  - Startle-elicited blinks were measured during the presentation of affective slides
      in order to investigate emotional responsiveness in 24 male healthy subjects and
      34 male schizophrenic patients. Although the two groups did not differ with
      regard to their subjective and autonomic responses to the slide stimuli, there
      was a significant difference between the groups in their responses to the startle
      probes. Patients rated low in affective expression showed a linear response
      pattern comparable to that of normal controls with largest amplitudes during
      unpleasant slides and smallest during pleasant slides. Patients without apparent
      deficit in affective expression showed a quadratic relationship with smaller
      blink amplitudes during both pleasant and unpleasant slides. Diminished affective
      expression rated on the basis of a clinical interview is not associated with a
      general attenuation of the blink reflex or of its modulation by exposure to
      emotional slides. Thus, we found no indication of an impairment in the perception
      of affective stimuli nor of reduced appreciation of pleasant stimuli (anhedonia)
      in these patients.

PMID- 8527469
TI  - Cognitive impairment and depression in the oldest old in a German and in U.S.
      communities.
AB  - Data on cognitive impairment in the oldest old is reported comparing two
      different samples, one in Munich, Germany, and the other in the United States
      (Epidemiologic Catchment Area [ECA] study). In both studies the Mini Mental State
      Examination (MMSE) was used for assessing cognitive impairment. The Munich sample
      consisted of 402 and the ECA sample of 827 very old people aged 85 years and
      above. The results indicate that approximately 40% of each sample scored below 24
      points in the MMSE indicating at least mild cognitive impairment. Severe
      cognitive impairment was found in 13.4% of the Munich and in 14.6% of the
      American sample. The prevalence of major depression was 1.4% in Munich and 2.0%
      in the ECA study, and dysthymia was found in 5.1% in the Munich and in 2.0% in
      the ECA sample aged 85 years and above. Persons living in institutions in both
      studies more frequently showed signs of cognitive impairment than those living in
      private households. The ECA sample, but not the Munich sample, showed a
      significantly higher prevalence of cognitive impairment for females and for the
      oldest age cohort above 90 years of age. Major depression was more frequent in
      Munich in persons living in institutions and in the ECA study among the oldest
      age cohort above 90 years of age. Dysthymia in both studies did not show any
      association with sociodemographic factors. Most of the excess comorbidity
      (cognitive impairment and depression) was observed among subjects with mild (and
      not with severe) cognitive impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527470
TI  - Becker-like muscular dystrophy in sisters.
AB  - Two sisters with muscular dystrophy of Becker-like clinical features presented.
      Muscle weakness was most prominent in the pelvic girdle, but in the elder sister
      the distal muscles of the lower extremities were also affected. The progression
      was different in the siblings: The older sister showed a more pronounced
      deterioration than the younger. The family history was negative in four
      generations including their brother and youngest sister. Serum creatinine kinase
      activities increased considerably. Electromyogram and muscle biopsy specimens
      revealed myopathic changes characteristic of muscular dystrophy. Chromosomal
      analysis confirmed normal 46,XX karyotype. DNA analysis with all cDNA probes
      spanning the entire dystrophin gene failed to reveal any intragenic deletion or
      duplication on southern blot. Immunohistochemistry for dystrophin using
      monoclonal antibodies against the rod and C-terminal domains showed normal
      continuous staining at the sarcolemma of the muscle fibers in the biopsy
      specimens of both patients. The results practically exclude the possibility of
      Xp21 myopathy, and it seems reasonable to classify these patients as having
      autosomal recessive childhood muscular dystrophy.

PMID- 8527471
TI  - Nonviral gene therapy: the promise of genes as pharmaceutical products.
AB  - Although most research on gene therapy has focused on the use of recombinant
      viruses to deliver genes to cells in vivo, progress also has been made toward
      developing nonviral, pharmaceutical formulations of genes for in vivo human
      therapy. Various methods for nonviral gene therapy have been proposed. Some
      approaches are aimed at developing "artificial viruses" that attempt to mimic the
      process of viral infection using synthetic materials. Others apply the theory and
      methods of advanced, particulate drug delivery to deliver DNA to select somatic
      targets. These approaches employ DNA complexes containing lipid, protein,
      peptide, or polymeric carriers as well as ligands capable of targeting the DNA
      complex to cell-surface receptors on the target cell and ligands for directing
      the intracellular trafficking of DNA to the nucleus. Nonviral systems have been
      used to deliver genes to the lung, liver, endothelium, epithelium, and tumor
      cells and have been shown to be generally safe. More than a dozen clinical trials
      are currently underway using nonviral systems for disease indications including
      cystic fibrosis and cancer. Future advances in nonviral systems will be based on
      an emerging appreciation of the biological constraints on the fate and function
      of DNA within the body and within the cell.

PMID- 8527472
TI  - Retroviral gene transfer into the intestinal epithelium.
AB  - The epithelial cells of the gastrointestinal tract may be attractive targets for
      somatic gene therapy. In these studies, we have used rats and mice to explore the
      feasibility of gene transfer into the small intestinal epithelium using
      retroviral vectors. The first series of experiments was conducted in mature
      Sprague-Dawley rats using an ecotropic retroviral vector that has bacterial beta
      galactosidase (beta-Gal) as the reporter gene. The vector was introduced into the
      lumen of ligated segments of terminal ileum. After a 4-hr exposure period, the
      ligatures were removed. Sham-operated animals were subjected to the same ligation
      procedure but received only tissue culture medium in the ligated segment. All
      animals were sacrificed 6 days later, and tissue from both the experimental
      segment and an upstream control segment was assessed for cytoplasmic beta-Gal
      activity using X-Gal histochemistry. Expression of the reporter gene was observed
      in the crypt epithelium of tissue exposed to the vector. In the villus
      epithelium, high background staining precluded accurate assessment of reporter
      gene expression. To obviate the latter problem, we sought an alternative reporter
      gene for which there would be no background staining in control animals. We
      repeated the experiments with beta-glucuronidase as the reporter gene in MPS VII
      mutant mice, which are devoid of this enzyme. In these studies, ileal segments
      exposed to the vector demonstrated expression of the reporter gene in both the
      crypt and villus epithelium 4 days after exposure. These results indicate that
      genes can be transferred into the intestinal epithelium using retroviral vectors
      introduced luminally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527473
TI  - In vivo delivery of human alpha-L-iduronidase in mice implanted with neo-organs.
AB  - Mucopolysaccharidose type I is a lysosomal storage disease caused by a deficiency
      in the enzyme alpha-L-iduronidase (IDUA). The existence of a secretory pathway
      for lysosomal enzymes and the capture of secreted molecules by distant cells
      through binding to mannose-6-phosphate receptors have provided a rationale for
      enzyme replacement therapy in lysosomal storage diseases. We have used
      genetically modified fibroblasts implanted into neo-organs as an in vivo delivery
      system for IDUA. The human IDUA cDNA was isolated and inserted into a retroviral
      vector where it was expressed from the phosphoglycerate kinase 1 gene promoter.
      MPS I fibroblasts transduced with this vector showed high levels of IDUA activity
      and secreted phosphorylated molecules that could be internalized by naive
      deficient cells. Neo-organs containing 2 x 10(7) IDUA-secreting cells were
      implanted into nude mice. Human and murine IDUA activities were measured in the
      liver and spleen of animals sacrificed 35-77 days after implantation. Human IDUA
      activity corresponded to 0.6-2.3% of the murine enzyme activity in the liver and
      to 0.1-0.3% in the spleen. These data indicated that human IDUA was secreted from
      neo-organs and internalized in distant tissues.

PMID- 8527474
TI  - A plasmid-based self-amplifying Sindbis virus vector.
AB  - Sindbis virus was used as a self-amplifying eukaryotic expression vector. A
      recombinant cDNA genome of this (+)-strand RNA virus was placed under the
      transcriptional control of a Rous sarcoma virus LTR (RSV) promoter. Transfection
      of this plasmid construct into mammalian cell lines (3T3, HepG2, and 293 cells)
      resulted in expression of the luciferase reporter gene. High-expression levels
      were also measured after transfection into primary rat myoblasts. In
      differentiated myotubes, expression levels generated by the Sindbis virus vector
      were up to 200 times higher than those obtained with a conventional RSV
      expression vector. In vivo expression was detected after injection of plasmid DNA
      into mouse quadriceps. In vivo expression was transient and undetectable by day
      16. This self-amplifying expression vector can be used for generating high-level
      expression of transgenes in vitro and in vivo. Its transient nature in vivo could
      allow for safe, short-term delivery of gene products in gene therapy protocols.
      It should facilitate the study of Sindbis and other RNA viruses.

PMID- 8527475
TI  - R-region cDNA inserts in retroviral vectors are compatible with virus replication
      and high-level protein synthesis from the insert.
AB  - Protein expression from retroviral vectors is often highest when the expressed
      cDNA is driven by the retroviral promoter. However, the typical retroviral vector
      design places the cDNA downstream of the retroviral packaging signal and far from
      the retroviral promoter. In an attempt to improve protein production levels from
      cDNAs expressed in retroviral vectors, we inserted the MyoD or the purine
      nucleoside phosphorylase (PNP) cDNAs into the R regions of both retroviral LTRs,
      close to the retroviral promoter and just upstream of the polyadenylation signal
      present in each long terminal repeat (LTR). These R-region double-copy vectors
      could be produced in unrearranged form, although the titer was about seven-fold
      lower than that of typical vectors. R-region positioning of the MyoD cDNA
      resulted in five-fold higher MyoD expression compared to MyoD expression in a
      typical vector, whereas PNP expression was not improved. Thus, R-region double
      copy vectors provide an alternative vector design that can improve protein
      expression from some cDNAs.

PMID- 8527476
TI  - Efficiency of in vivo gene transfer using murine retroviral vectors is strain
      dependent in mice.
AB  - Retroviral vectors can be used to transduce cultured cells at high frequencies,
      but efficient transduction of target cells in vivo has proved difficult and
      little is known about the factors that influence the efficiency of retroviral
      infection. Many commonly used mouse strains harbor endogenous C-type proviruses,
      some of which are expressed and have circulating antibodies against the viral
      envelope glycoproteins that cross-react with the Moloney strain of murine
      leukemia virus (MoMLV), from which most current retroviral vectors are derived.
      We have investigated the relative efficiency of retroviral-mediated gene transfer
      into regenerating skeletal muscle of a variety of mouse strains using a MoMLV
      based vector. Humoral immune competence and interference between endogenous MLVs
      and exogenous recombinant MoMLV were observed to affect the efficiency of
      retroviral-mediated transfection in vivo. Our results indicate that the mouse
      genetic background and immune status need to be considered when choosing a
      preclinical model for in vivo retroviral-mediated gene transfer.

PMID- 8527477
TI  - Regenerating cells in human airway surface epithelium represent preferential
      targets for recombinant adenovirus.
AB  - To investigate the efficiency of adenovirus-mediated gene delivery in
      regenerating human respiratory epithelium, we have performed infections with an
      E1- and E3-deleted type 5 recombinant adenovirus containing the Escherichia coli
      LacZ reporter gene on different culture models of regenerating human nasal polyp
      surface epithelium. These models included: (i) an ex vivo organ culture of nasal
      polyp tissue, (ii) an explant outgrowth cell culture, and (iii) an in vitro wound
      repair model, on dissociated cells. In ex vivo nasal polyp tissue, transduced
      cells were not detected in normal pseudostratified areas, but were found in areas
      of the surface epithelium with a morphology reminiscent of regenerating airway
      tissue. In the explant outgrowth cell culture, adenovirus-infected cells were
      preferentially detected at the periphery of the outgrowth. These transducible
      epithelial cells, representative of epithelial cells present in vivo during the
      process of surface airway epithelium regeneration, were shown to be migrating and
      poorly differentiated cells, which were proliferating or not. In the in vitro
      wound repair model, the efficiency of cell transduction was much higher in cells
      present in the wound area than in those far from the wound area. These results
      indicate that regenerating cells from human airway surface epithelium represent
      preferential targets for transgene expression, and suggest that efficiency of
      CFTR gene transfer by recombinant adenovirus vectors may be higher in
      regenerating CF airway mucosa than in normal tissue. However, since these cells
      do not show endogenous CFTR expression, the relevance of their preferential
      transduction for the functional correction of the ion transport defect in cystic
      fibrosis needs further investigations.

PMID- 8527478
TI  - Use of sodium butyrate to enhance production of retroviral vectors expressing
      CFTR cDNA.
AB  - Previously, we constructed a retrovirus vector (LCFSN) for transduction and
      expression of the cDNA encoding the normal human cystic fibrosis transmembrane
      conductance regulator (CFTR). The titer of virus from amphotropic packaging cells
      producing the LCFSN vector was low (10(3)-10(4) infectious units/ml). In an
      attempt to increase virus production, we used sodium butyrate (NaB) to treat
      murine retrovirus packaging cells producing this vector. NaB treatment increased
      the production of LCFSN from between 20-fold to greater than 1,000-fold,
      depending upon the producer clone, thereby resulting in virus titers up to about
      1 x 10(7) infectious units/ml. This induction of virus titer could be accounted
      for, at least in part, by an increase in steady-state levels of full-length
      vector RNA within the producer cells. With some clonal producer cell lines,
      lowering the temperature of the virus harvest in combination with NaB treatment
      resulted in an apparent synergistic increase in virus production. The production
      of retrovirus vectors containing genes other than CFTR could also be increased by
      NaB treatment, although the enhancement in titer was modest (2-fold to 10-fold).
      The increase in virus production was not accompanied by an induction of
      replication-competent helper virus. NaB treatment also increased the transient
      production of retroviral vectors following DNA-mediated transfection into
      packaging cells such that virus titers of greater than 10(6) infectious units/ml
      could be readily attained.

PMID- 8527479
TI  - Inducible, high-level production of infectious murine leukemia retroviral vector
      particles pseudotyped with vesicular stomatitis virus G envelope protein.
AB  - Murine leukemia viruses (MuLV) have been adapted for use as gene transfer vectors
      for experimental and human gene therapy applications. Their utility for these
      purposes has been circumscribed by the limited host range and relatively low
      titer of available producer clones. Pseudotyping of MuLV particles with the
      vesicular stomatitis virus envelope protein (VSV-G), expressed transiently in
      cells producing MuLV Gag and Pol proteins, has yielded vector preparations with a
      broader host range that can be concentrated by ultracentrifugation. We have
      explored the use of steroid-inducible and tetracycline-modulated promoter systems
      (necessary because the VSV-G protein is toxic to cells when constitutively
      expressed) to derive stable producer cell lines capable of substantial production
      of VSV-G pseudotyped MuLV particles. A packaging cell line and producer clones
      capable of expressing a chimeric transcription factor, composed of the
      tetracycline repressor (tetR) and the VP16 trans-activating sequences of herpes
      simplex virus VP16 gene and containing the VSV-G coding sequences linked to a
      minimal promoter having seven tandem copies of the tetracycline responsive
      operator (tetO), exhibited high levels of VSV-G protein expression when cultured
      in the absence of tetracycline. Vector particles, produced at titers of 10(5)
      10(6) infectious colony forming units per ml (cfu/ml), could be concentrated
      effectively by ultracentrifugation yielding vector preparations having a titer of
      10(9) cfu/ml. These cell lines grew normally when VSV-G protein expression was
      repressed by tetracycline. Such producer clones hold promise for future human
      gene therapy applications.

PMID- 8527480
TI  - In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic
      house cat, using an adenoviral vector containing a bifunctional fusion protein,
      GAL-TEK.
AB  - We evaluated the ability of a replication-deficient, recombinant adenoviral
      vector to transfer the bifunctional gene GAL-TEK, which expresses a
      marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in
      situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for
      histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk
      gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce
      selective tumor cell killing. GAL-TEK bifunctional marking and cell killing
      activities were tested in vitro after adenoviral vector infection of HT1080 human
      fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as
      HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective
      cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose
      spontaneously or were induced by vaccine, we determined experimentally the
      administration routes and times required for optimum GAL-TEK gene transfer by
      beta-Gal histological staining and reverse transcriptase polymerase chain
      reaction to the multiple compartments of the growing fibrosarcomas consonant with
      minimizing collateral infection of neighboring tissues and other unwanted side
      effects.

PMID- 8527481
TI  - Retroviral gene transfer into retinal pigment epithelial cells followed by
      transplantation into rat retina.
AB  - In this preliminary report, we describe a technique for gene transfer into the
      retina using a retrovirus vector. We transferred the bacterial LacZ gene and the
      neomycin-resistance gene into pigmented wild-type rat retinal pigment epithelial
      (RPE) cells in culture. The RPE culture was exposed to retrovirus, and infected
      cells were selected with a neomycin analog (G418). The LacZ gene product was
      detected by X-Gal histochemistry in 95-100% of drug-resistant cells. These
      genetically labeled cells were transplanted into the subretinal space of two 15-
      to 25-day-old albino RCS rats, which have an inherited retinal degeneration
      syndrome. The retinas were fixed and stained with X-Gal at 3 and 6 weeks after
      transplantation. At both time points, pigmented, LacZ-containing cells were seen
      in the subretinal space. Further, there were several rows of photoreceptor nuclei
      in the transplant area of the approximately 2-month-old rats, while in the
      control contralateral eye the photoreceptor nuclei were virtually absent, as for
      untreated animals, suggesting that the transplanted LacZ-marked, wild-type RPE
      cells may have helped preserve photoreceptors. The technique for gene transfer
      into RPEs followed by transplantation thus provides a means for gene therapy in
      organisms with a genetic defect in RPE cells.

PMID- 8527482
TI  - Stereotactic injection of herpes simplex thymidine kinase vector producer cells
      (PA317-G1Tk1SvNa.7) and intravenous ganciclovir for the treatment of progressive
      or recurrent primary supratentorial pediatric malignant brain tumors.
AB  - This study will evaluate the safety and efficacy of in vivo gene transfer of the
      herpes simplex thymidine kinase (HSV-Tk1) gene using PA317/G1Tk1SvNa.7 vector
      producer cells (VPC) in pediatric patients with progressive or recurrent primary
      supratentorial malignant brain tumors. Insertion of the HSV-Tk1 gene confers a
      sensitivity to the anti-herpes drug ganciclovir. It has been demonstrated that
      the direct injection of HSV-Tk vector producer cells into growing tumors in
      animals can result in their complete destruction with ganciclovir therapy. This
      selective destruction of growing tumors in situ is thought to result from the
      transfer of the HSV-Tk gene into the tumor cells and the production of toxic
      ganciclovir metabolites which result from the interaction of HSV-Tk and
      ganciclovir. This procedure can result in the cure of some experimental animals
      with limited systemic toxicity due to selective gene transfer into tumors. This
      clinical trial will focus on maximizing the relative number of vector producer
      cells to the tumor mass by stereotactically injecting VPCs into the tumor mass.
      Children with progressive or recurrent primary supratentorial malignant brain
      tumor which is accessible to stereotactic injection will be evaluated for the
      extent and location(s) of their disease before being entered into the study.
      Fifteen days after stereotactic injection of the tumor mass, ganciclovir will be
      administered at 5 mg/kg IV b.i.d. for 14 days. Upon completion of the treatment
      with HSV-Tk1 vector producer cells and ganciclovir, the patient will be followed
      monthly for the first three months, then every two months for the next twenty-one
      months, and annually for life thereafter.

PMID- 8527483
TI  - ADP-ribosylation reactions.
AB  - ADP-ribosylation reactions have been studied now for over 30 years. They came to
      light originally in studies of some bacterial toxins, which turned out to be mono
      ADP-ribosyl transferases. Subsequently, endogenous mono-ADP-ribosyltransferases
      were discovered. Although the substrates of the toxins are always so-called G
      proteins, the substrate for a muscle mono-ADP-ribosyl transferase has been shown
      to be an extra-cellular cell adhesion molecule. A new pathway of NAD catabolism
      is the recently described cyclic ADP-ribose; this seems to be involved in calcium
      metabolism. Just under 30 years ago, poly(ADP-ribose) polymerase was discovered.
      From protein studies as well as from recent molecular biology, some amino acids
      essential for the enzyme activity or for binding to DNA have been identified. I
      suggest that poly(ADP-ribose) polymerase has several related functions in
      maintaining the integrity of the genome in eukaryotic cells. The highly-charged
      polymer, poly(ADP-ribose), is always made when free, ie naked DNA ends appear, in
      order to ensure the correct processing of these DNA breaks. In particular, the
      polymer may act to prevent DNA recombination reactions that would interfere with
      DNA repair. In addition, the polymer may protect the free DNA end from
      exonuclease action, and thirdly, it may unravel the chromatin structure. This
      suggests that this enzyme is not a necessary component of the process of DNA
      excision repair, but that this enzyme is required for correct and efficient DNA
      excision repair.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527484
TI  - Characterization of mammalian ADP-ribosylation cycles.
AB  - NAD:arginine ADP-ribosyltransferases catalyze the transfer of the ADP-ribose
      moiety from NAD to an arginine in an acceptor protein, whereas ADP
      ribosylarginine hydrolases remove ADP-ribose, regenerating free arginine and
      completing an ADP-ribosylation cycle. A family of four mono-ADP
      ribosyltransferases was isolated and characterized from turkey erythrocytes.
      Transferases from rabbit and human skeletal muscle were cloned. The muscle
      transferases are glycosylphosphatidylinositol-anchored proteins and highly
      conserved across mammalian species. The rat T cell alloantigen RT6.2 has
      significant amino acid sequence identity to the muscle ADP-ribosyltransferase.
      Mammalian cells transformed with the RT6.2 coding region cDNA expressed NAD
      glycohydrolase activity. Sequences of RT6.2, rabbit muscle transferase and
      several of the bacterial toxin ADP-ribosyltransferases contain regions of amino
      acid similarity which, in the bacterial toxin ADP-ribosyltransferases, form the
      NAD-binding and active-site domains. ADP-ribosylarginine hydrolase, initially
      purified from turkey erythrocytes, was cloned from rat, mouse, and human brain.
      Deduced amino acid sequences of the rat and mouse hydrolases were 94% identical
      with five conserved cysteines whereas the human hydrolase sequence was 83%
      identical to that of the rat, with four conserved cysteines. It is unclear how an
      intracellular hydrolase acts in concert with a surface ADP-ribosyltransferase.

PMID- 8527485
TI  - Studies on the active-site structure of C3-like exoenzymes: involvement of
      glutamic acid in catalysis of ADP-ribosylation.
AB  - Various C3-like ADP-ribosyltransferases like Clostridium botulinum exoenzyme C3,
      C limosum transferase, B cereus transferase and a transferase from Staphylococcus
      aureus (EDIN) selectively modify the low-molecular mass GTP-binding proteins
      RhoA,B,C. UV-irradiation of C limosum transferase in the presence of [carbonyl
      14C]NAD resulted in radiolabeling of Glu-174. Concomitantly, ADP
      ribosyltransferase and NAD glycohydrolase activities were inhibited. Site
      directed mutagenesis of Glu-174 (E174D, E174Q) which resulted in more than 1000
      fold reduction of enzyme activity, suggests that the glutamic acid residue is
      essentially involved in the catalytic action of C3-like transferases. These
      findings support the view that all bacterial ADP-ribosyltransferases share a
      similar active-site structure.

PMID- 8527486
TI  - A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1
      subunit.
AB  - Pertussis toxin is a complex protein composed of five different subunits, named
      S1 through S5 and arranged in an A-B structure. The B oligomer, composed of S2
      through S5, is the receptor-binding moiety, and the A promoter, composed of S1,
      is the enzymatically active moiety. S1 catalyzes the ADP-ribosylation of a
      cysteine in the alpha subunit of heterotrimeric G proteins. In the absence of G
      proteins it also catalyzes the cleavage of NAD+ into ADP-ribose and nicotinamide.
      Molecular dissection has indicated that the C-terminal domain of S1 is involved
      in G-protein binding, while the N-terminal domain, homologous to other ADP
      ribosylating toxins, contains the NAD(+)-binding site and the residues involved
      in catalysis. By site-directed mutagenesis and kinetic analyses Glu-129 and His
      35 were identified as the catalytic residues. Glutamates analogous to Glu-129 are
      found in all studied ADP-ribosylating toxins, while His-35 is less well
      conserved. This suggests that Glu-129 acts on the common substrate NAD+, whereas
      His-35 plays its role on the acceptor substrates. We propose a mechanism in which
      Glu-129 exerts its action on the 2'-OH group of the NAD+ ribose, thereby
      facilitating the formation of an oxocarbonium-like intermediate and the weakening
      of the N-glycosidic bond. His-35 could increase the nucleophilicity of the
      cysteine in the G protein or the water molecule to attack the weakened N
      glycosidic bond of NAD+ and yield the products of the reaction.

PMID- 8527487
TI  - NAD glycohydrolases and the metabolism of cyclic ADP-ribose.
AB  - Cyclic ADP-ribose is a recently discovered metabolite of NAD that functions in
      cellular calcium signalling. The discovery that NAD glycohydrolases can catalyze
      the synthesis and hydrolysis of cyclic ADP-ribose has renewed interest in this
      class of ADP-ribose transferring enzymes that were discovered over 50 years ago.

PMID- 8527488
TI  - Cyclic ADP-ribose and its metabolic enzymes.
AB  - Cyclic ADP-ribose (cADPR) is a recently discovered cyclic nucleotide with Ca2+
      signaling functions. There is a growing recognition that it is an endogenous
      modulator of the Ca(2+)-induced Ca2+ release mechanism in cells. The cyclic
      structure of cADPR has now been confirmed by x-ray crystallography. A series of
      analogs of cADPR has been synthesized, including antagonists and a novel analog,
      cyclic GDP-ribose. Considerable progress has been made in characterizing ADP
      ribosyl cyclase, the synthetic enzyme, and cADPR hydrolase, the hydrolytic
      enzyme. A new class of bifunctional enzymes has been identified which catalyses
      both the synthesis and hydrolysis of cADPR. CD38, a lymphocyte differentiation
      antigen, is a member of this class. The understanding of the mechanisms of
      regulation of the metabolic enzymes and signaling by cADPR is likely to have
      important implications and several possibilities are discussed in this article.

PMID- 8527489
TI  - New aspects of the physiological significance of NAD, poly ADP-ribose and cyclic
      ADP-ribose.
AB  - Cyclic ADP-ribose is generated from NAD+ in glucose-stimulated beta-cells by
      CD38. Cyclic ADP-ribose mobilizes Ca2+ from the endoplasmic reticulum to secrete
      insulin. The amino acid residues of Cys-119 and Cys-201 in CD38 are essential for
      the synthesis and hydrolysis of cyclic ADP-ribose.

PMID- 8527490
TI  - NAD and poly(ADP-ribose) regulation of proteins involved in response to cellular
      stress and DNA damage.

PMID- 8527491
TI  - Cell differentiation induced by poly(ADP-ribose) synthetase inhibitors.
AB  - From a survey of about 400 compounds, we found a number of potent and specific
      inhibitors of poly(ADP-ribose) synthetase. Two new classes of inhibitors include
      vesnarinones and heterocyclic amines. Although the inhibitory activity was not
      very strong, several of these classes of inhibitors proved to induce most
      efficiently differentiation of murine teratocarcinoma EC cells in culture; for
      example, 70 microM benzylvesnarinone or 1 mM PhIP effected almost complete change
      in cell morphology in 5 to 7 days. Analyses of poly(ADP-ribose) synthesis and NAD
      concentrations in EC cells after treatment with a differentiation inducer
      suggested that poly(ADP-ribose) might play a role at an initiation stage of cell
      differentiation.

PMID- 8527492
TI  - Reversion of malignant phenotype by 5-iodo-6-amino-1,2-benzopyrone a non
      covalently binding ligand of poly(ADP-ribose) polymerase.
AB  - A non-covalently binding inhibitory ligand of poly(ADP-ribose) polymerase, 5-iodo
      6-amino-1,2-benzopyrone, when incubated at 5-600 microM external concentration
      with an E-ras-transformed tumorigenic cell line or with human prostatic carcinoma
      cells for 40 to 60 days converts both cancer cells to a non-tumorigenic phenotype
      that is characterized by drastic changes in cell morphology, absence of
      tumorigenicity in nude mice, and a high rate of aerobic glycolysis.

PMID- 8527493
TI  - Activation of poly(ADP-ribose)polymerase in apoptotic human cells.
AB  - We have studied the effect of the chemotherapeutic drug VP-16 (etoposide) on the
      metabolism of HeLa cells by analysing different cellular parameters considered as
      markers of apoptosis. Typical features such as chromatin condensation and
      internucleosomal DNA cleavage are visible in HeLa cells exposed to VP-16. We
      investigated whether the appearance of small-sized DNA fragments could regulate
      the ADP-ribosylation process. To this purpose, we have analysed, by means of the
      activity gel technique; the structural and catalytical properties of poly(ADP
      ribose)polymerase. In extracts from cells where etoposide-induced DNA
      fragmentation occurred, we have shown that the label of the autoribosylated form
      of the enzyme is greatly increased even if the amount of the protein remains
      constant. This phenomenon is completely abolished in cells preincubated with
      poly(ADP-ribose)polymerase inhibitor, 3-aminobenzamide. After VP-16
      administration, we have observed that the level of NAD is not heavily decreased.
      It is widely agreed that zinc exerts an inhibitory effect on the endonuclease(s)
      responsible for the fragmentation of DNA during apoptosis. After incubation of
      cells with zinc/VP-16 we have found the occurrence of apoptotic parameters even
      in the absence of internucleosomal DNA cleavage. The inhibition of DNA
      fragmentation prevents the activation of poly(ADP-ribose)polymerase activity.
      These results indicate that the activation of the enzyme towards the
      automodification reaction is strictly dependent on the appearance of DNA
      internucleosomal fragments and could represent a way to control enzyme activity.

PMID- 8527494
TI  - Progress in identifying clinical relevance of inhibition, stimulation and
      measurements of poly ADP-ribosylation.
AB  - Our laboratory, in collaboration with Oxigene Inc, has been involved in
      identifying commercially feasible clinical applications of measurement or
      modulation of ADP-ribosylation as a core technology. For this purpose a pivotal
      regulatory role for ADP-ribosylation in the repair of DNA lesions leading to
      cytotoxic as well as mutagenic events has been hypothesized. A new class of DNA
      repair inhibitors, the N-substituted benzamides, has been identified which can
      react with radiation to produce reactive intermediates that oxidize thiol amino
      acids. Their proposed mechanisms of action are two-fold: ie they can interact
      with radiation: i) to directly enhance DNA damage; and ii) to react with thiols
      in the zinc finger DNA binding domain of poly ADP-ribosyl transferase to inhibit
      DNA repair and thereby increase DNA damage. Sensamide, a clinically relevant
      formulation of metoclopramide which is an N-substituted benzamide, has indicated
      enhancement of tumor response and survival in patients with inoperable squamous
      cell carcinoma of the lung when it was administered as a radiosensitizer in a
      phase I/II trial and compared to historical controls. A mechanism of endogenous
      regulation of human mononuclear leucocyte ADP-ribosylation has been identified to
      be HOCl/N-chloramine production via the oxidative burst of phagocytes. HOCl/N
      chloramines are potent oxidants of thiol-containing proteins. Quantitative
      estimation of N-chloramine sensitive plasma thiols has been identified as an
      effective surrogate measure of leucocyte poly ADPRT.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8527495
TI  - Evaluating the role of niacin in human carcinogenesis.
AB  - Our understanding of the role of ADP-ribose polymer metabolism in limiting
      carcinogenic events and the dependence of this metabolism on cellular NAD levels
      predicts that niacin deficiency leading to reduced NAD levels may enhance
      carcinogenesis. This prediction has led us to initiate studies to evaluate the
      potential of niacin as a preventive factor in human cancer. The first approach
      involves development of a method to assess biochemically niacin status in humans
      using intracellular NAD derived from whole blood, primarily erythrocytes, as the
      relevant marker of niacin status. We have shown that erythrocyte NAD content
      varies by as much as 12-fold within a population and can be modulated readily by
      supplementation. A second approach to testing this hypothesis involves
      understanding the relationship of dietary niacin, circulating levels of NAD
      precursors (nicotinamide and nicotinic acid) and NAD in target tissues for human
      cancer. Current analytical methods for quantification of plasma levels of
      nicotinic acid and nicotinamide following intake in the dietary range are not
      sufficient. Thus, we have developed a GC-MS method for the rapid, sensitive, and
      selective determination of both nicotinamide and nicotinic acid in plasma. These
      methods will now allow assessment of niacin metabolism in humans that could lead
      to a new understanding of niacin in prevention of cancer.

PMID- 8527496
TI  - Linear and nonlinear stiffness and friction in biological rhythmic movements.
AB  - Biological rhythmic movements can be viewed as instances of self-sustained
      oscillators. Auto-oscillatory phenomena must involve a nonlinear friction
      function, and usually involve a nonlinear elastic function. With respect to
      rhythmic movements, the question is: What kinds of nonlinear friction and elastic
      functions are involved? The nonlinear friction functions of the kind identified
      by Rayleigh (involving terms such as theta3) and van der Pol (involving terms
      such as theta2theta), and the nonlinear elastic functions identified by Duffing
      (involving terms such as theta3), constitute elementary nonlinear components for
      the assembling of self-sustained oscillators, Recently, additional elementary
      nonlinear friction and stiffness functions expressed, respectively, through terms
      such as theta2theta3 and thetatheta2, and a methodology for evaluating the
      contribution of the elementary components to any given cyclic activity have been
      identified. The methodology uses a quantification of the continuous deviation of
      oscillatory motion from ideal (harmonic) motion. Multiple regression of this
      quantity on the elementary linear and nonlinear terms reveals the individual
      contribution of each term to the oscillator's non-harmonic behavior. In the
      present article the methodology was applied to the data from three experiments in
      which human subjects produced pendular rhythmic movements under manipulations of
      rotational inertia (experiment 1), rotational inertia and frequency (experiment
      2), and rotational inertia and amplitude (experiment 3). The analysis revealed
      that the pendular oscillators assembled in the three experiments were
      compositionally rich, braiding linear and nonlinear friction and elastic
      functions in a manner that depended on the nature of the task.

PMID- 8527497
TI  - Open-loop simulations of the primate saccadic system using burst cell discharge
      from the superior colliculus.
AB  - Saccade-related burst neurons (SRBNs) in the monkey superior colliculus (SC) have
      been hypothesized to provide the brainstem saccadic burst generator with the
      dynamic error signal and the movement initiating trigger signal. To test this
      claim, we performed two sets of open-loop simulations on a burst generator model
      with the local feedback disconnected using experimentally obtained SRBN activity
      as both the driving and trigger signal inputs to the model. First, using neural
      data obtained from cells located near the middle of the rostral to caudal extent
      of the SC, the internal parameters of the model were optimized by means of a
      stochastic hill-climbing algorithm to produce an intermediate-sized saccade. The
      parameter values obtained from the optimization were then fixed and additional
      simulations were done using the experimental data from rostral collicular neurons
      (small saccades) and from more caudal neurons (large saccades); the model
      generated realistic saccades, matching both position and velocity profiles of
      real saccades to the centers of the movement fields of all these cells. Second,
      the model was driven by SRBN activity affiliated with interrupted saccades, the
      resumed eye movements observed following electrical stimulation of the omnipause
      region. Once again, the model produced eye movements that closely resembled the
      interrupted saccades produced by such simulations, but minor readjustment of
      parameters reflecting the weight of the projection of the trigger signal was
      required. Our study demonstrates that a model of the burst generator produces
      reasonably realistic saccades when driven with actual samples of SRBN discharges.

PMID- 8527498
TI  - Prediction of a moving target's position in fast goal-directed action.
AB  - Subjects made fast goal-directed arm movements towards moving targets. In some
      cases, the perceived direction of target motion was manipulated by moving the
      background. By comparing the trajectories towards moving targets with those
      towards static targets, we determined the position towards which subjects were
      aiming at movement onset. We showed that this position was an extrapolation in
      the target's perceived direction from its position at that moment using its
      perceived direction of motion. If subjects were to continue to extrapolate in the
      perceived direction of target motion from the position at which they perceive the
      target at each instant, the error would decrease during the movements. By
      analysing the differences between subjects' arm movements towards targets moving
      in different (apparent) directions with a linear second-order model, we show that
      the reduction in the error that this predicts is not enough to explain how
      subjects compensate for their initial misjudgments.

PMID- 8527499
TI  - The connectivity of the brain: multi-level quantitative analysis.
AB  - We develop a mathematical formalism or calculating connectivity volumes generated
      by specific topologies with various physical packing strategies. We consider four
      topologies (full, random, nearest-neighbor, and modular connectivity) and three
      physical models: (i) interior packing, where neurons and connection fibers are
      intermixed, (ii) sheeted packing where neurons are located on a sheet with fibers
      running underneath, and (iii) exterior packing where the neurons are located at
      the surfaces of a cube or sphere with fibers taking up the internal volume. By
      extensive cross-referencing of available human neuroanatomical data we produce a
      consistent set of parameters for the whole brain, the cerebral cortex, and the
      cerebellar cortex. By comparing these inferred values with those predicted by the
      expressions, we draw the following general conclusions for the human brain,
      cortex, and cerebellum: (i) Interior packing is less efficient than exterior
      packing (in a sphere). (ii) Fully and randomly connected topologies are extremely
      inefficient. More specifically we find evidence that different topologies and
      physical packing strategies might be used at different scales. (iii) For the
      human brain at a macro-structural level, modular topologies on an exterior sphere
      approach the data most closely. (iv) On a mesostructural level, laminarization
      and columnarization are evidence of the superior efficiency of organizing the
      wiring as sheets. (v) Within sheets, microstructures emerge in which interior
      models are shown to be the most efficient. With regard to interspecies
      similarities and differences we conjecture (vi) that the remarkable constancy of
      number of neurons per underlying square millimeter of cortex may be the result of
      evolution minimizing interneuron distance in grey matter, and (vii) that the
      topologies that best fit the human brain data should not be assumed to apply to
      other mammals, such as the mouse for which we show that a random topology may be
      feasible for the cortex.

PMID- 8527500
TI  - On deriving analyser characteristics from summation-at-threshold data.
AB  - It has been proved that a detection process may be accounted for by a simple two
      state model consisting of a collection of linear analysers followed by a maximum
      output decision rule provided that a set of all threshold stimuli is convex. A
      non-parametrical method to identify the analysers constituting such a model is
      proposed.

PMID- 8527501
TI  - A 'tachometer' feedback model of smooth pursuit eye movements.
AB  - A new model of smooth pursuit eye movements is presented. We begin by formally
      analyzing the stability of the proportional-derivative (PD) model of smooth
      pursuit eye movements using Pontryagin's theory. The PD model is the linearized
      version of the nonlinear Krauzlis-Lisberger (KL) model. We show that the PD model
      fails to account for the experimentally observed dependence of the eye velocity
      damping ratio and the oscillation period on the total delay in the feedback loop.
      To explain the data, a new 'tachometer' feedback model, based on an efference
      copy signal of eye acceleration, is proposed and analyzed by computer simulation.
      The model predicts some salient features of monkey pursuit data and suggests a
      functional role for the extraretinal input to the medial superior temporal area
      (MST).

PMID- 8527502
TI  - Preparation of spermatogonia, spermatocytes, and round spermatids for analysis of
      gene expression using fluorescence-activated cell sorting.
AB  - A new method is described for the purification of spermatogenic cell populations
      from mouse testis. Through use of this method, it is possible to purify
      leptotene, zygotene, and pachytene primary spermatocytes as well as round
      spermatids from adult mouse testis. In addition, spermatogonial populations can
      be purified from mice at 9 days postpartum. The leptotene and zygotene primary
      spermatocytes that can be prepared by this method are impossible to separate
      successfully by the unit gravity method. The cells were used to prepare RNA for
      reverse transcriptase-polymerase chain reactions.

PMID- 8527503
TI  - Histological characteristics of the uterine endometrium and corpus luteum during
      early embryogenesis and the relationship to embryonic mortality in the domestic
      cat.
AB  - Pregnancy rates are low and litter sizes generally small when assisted
      reproduction techniques are used in gonadotropin-treated felid (cat) species. A
      prerequisite to determining whether or not abnormal morphological changes in the
      uterine lumen or corpus luteum (CL) are related to this reproductive failure is
      the documentation of normal histological kinetics during natural embryogenesis.
      This study characterized the histological changes of the endometrium and ovarian
      CL during the early stages of preimplantation embryonic development in the
      naturally estrous, mated queen. The purpose was to 1) develop a system for dating
      the cat endometrium and CL of early pregnancy; 2) document the frequency of
      abnormal uterine and CL history under natural mating conditions; and 3) compare
      histological traits of queens producing good- vs. poor-quality embryos. Naturally
      estrous, mated queens were ovariohysterectomized at 64 h (n = 8), 76 h (n = 11),
      100 h (n = 8), 124 h (n = 7), 148 h (n = 6), or 480 h (n = 8) after first
      copulation. Embryos collected from oviductal and uterine flushings were graded
      for quality, and uteri and ovaries were fixed in formalin. Fixed tissue sections
      were stained and multiple histological traits described for each uterine
      (endometrial height, endometrial vacuolation, percentage of glandular cells with
      subnuclear vacuoles, number of mitoses, nuclear-to-cytoplasmic ratio) and ovarian
      (presence of tertiary follicles, vacuolation of luteal cell cytoplasm, luteal
      cell shape) sample. Modest histological changes were observed at each time point,
      and these were documented in detail. The most prominent modifications occurred at
      124 h after first copulation and included thickening of the endometrium,
      straightening of the glands, increased cytoplasmic vacuolation, and increased
      epithelial height. Of 15 queens failing to produce good-quality embryos, only 4
      expressed unusual histological characteristics; and 3 of 25 queens producing only
      high-quality embryos exhibited abnormal uterine or CL cellular integrity.
      Therefore, aberrant histological changes are not primarily responsible for
      failure of the naturally estrous, mated queen to produce good-quality embryos.
      Furthermore, a normative database now is available to date the endometrium and CL
      of early pregnancy and to examine the impact of exogenous gonadotropins and
      assisted techniques on uterine/CL structure and function.

PMID- 8527504
TI  - Relationship of circulating steroid hormones, luteal luteinizing hormone receptor
      and progesterone concentration, and embryonic mortality during early
      embryogenesis in the domestic cat.
AB  - Serum hormones, corpus luteum (CL) progesterone, and CL LH receptors were
      characterized and interrelated to ovarian follicle and CL number and
      preimplantation embryo quality/survival in the cat. Blood samples were collected
      from queens ovariohysterectomized at 64 (n = 7), 76 (n = 11), 100 (n = 8), 124 (n
      = 7), 148 (n = 6), or 480 (n = 8) h after first copulation (3-times-daily matings
      on Days 2 and 3 of estrus). Ovarian CL were enucleated, weighed, and bisected;
      one hemi-CL was assayed for progesterone and the other for LH receptors. Serum
      was assessed for estradiol-17 beta and progesterone. Serum estradiol-17 beta
      concentrations did not return (p > 0.05) to baseline approximately 20 pg/ml)
      until 124 h after first copulation, whereas serum progesterone began to increase
      (> 1 ng/ml) by 76 h, was elevated (p < 0.05) by 124 h, and continued to rise
      thereafter. Serum progesterone was highly correlated with CL mass and LH receptor
      and progesterone concentration (range, r = 0.69-0.82; p < 0.01). CL progesterone
      and LH receptor concentrations were similar (p > 0.05) at 64 and 76 h, and both
      increased (p < 0.05) at subsequent time intervals and were correlated closely (r
      = 0.65; p < 0.01). Although ovarian CL were distinct and well organized by 64 h,
      pronounced elevations in serum progesterone and CL LH receptors and progesterone
      did not occur until at least 36 h later. The rapid increase in serum progesterone
      concentrations between 100 and 148 h was related to accelerated LH receptor
      synthesis and CL progesterone production and not entirely to enhanced CL
      growth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527505
TI  - Relaxin stimulates interstitial collagenase activity in cultured uterine cervical
      cells from nonpregnant and pregnant but not immature guinea pigs; estradiol-17
      beta restores relaxin's effect in immature cervical cells.
AB  - Relaxin has been implicated in dilatation of the cervix at parturition.
      Dilatation of the guinea pig cervix at parturition is mediated by an estrogen
      induced degradation of type I collagen by interstitial collagenase (matrix
      metalloproteinase I, MMPI). This study was designed to test the hypothesis that
      human recombinant relaxin (hrR) stimulates MMPI activity in cultured guinea pig
      cervical cells. Primary cervical monolayer cultures from immature, adult
      nonpregnant, and 50-day-pregnant Hartley guinea pigs were exposed to hrR (1-1000
      ng/ml) daily for 3 days in serum-free Dulbecco's Modified Eagle's Medium (DMEM).
      The effect of priming immature cells with estradiol-17 beta (E2, 10(-6) M) daily
      for 3 days prior to treatment with hrR was also determined. Tissue inhibitors of
      metalloproteinases were inactivated by reduction, alkylation, and dialysis. MMPI
      activity at 96 h was assayed via a highly sensitive and specific assay that
      utilizes [3H]telopeptide-free type I collagen as a substrate. Aminophenylmercuric
      acetate (0.5 mM) was used to activate latent MMPI. Phenanthroline-1,10 (1 mM), a
      known inhibitor of metalloproteinases, was used as a blank control. Phorbol-12
      myristate-13-acetate (PMA, 10(-8) M), a known stimulator of MMPI biosynthesis,
      was used as a positive control. The hrR in serum-free DMEM had no significant
      effect on cell number in nonpregnant, 50-day-pregnant, E2-primed, or nonprimed
      immature animals. It stimulated MMPI activity in a dose-dependent manner with a
      maximum response at 10 ng/ml in nonpregnant (2-fold), 50-day-pregnant (3-fold),
      and E2-primed immature (3-fold) animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527506
TI  - Isolation and characterization of a 30-kDa endometrial glycoprotein synthesized
      during the estrous cycle and early pregnancy of the pig.
AB  - Endometrial polypeptide synthesis, which is regulated through ovarian steroid
      secretion and steroid production by the developing conceptus, not only provides
      the necessary secretory components vital to conceptus development but also
      presents the adhesive changes in the epithelial surface essential for conceptus
      attachment. In the present study, a 30-kDa, basic endometrial glycoprotein
      (pGP30) was isolated and characterized during the estrous cycle and early
      pregnancy of the pig. Uterine flushings and endometrial culture media were
      obtained from gilts on Days 0, 5, 10, 12, 15, and 18 of the estrous cycle and
      Days 10, 12, 15, and 18 of pregnancy. A polyclonal antibody was generated to
      pGP30 after isolation of medium from Day 15 pregnant endometrial cultures
      separated by gel filtration and PAGE. Western blot analysis indicated that the
      antiserum reacted with isoforms of pGP30 and cross-reacted with a 90-kDa
      component in serum that was not removed after cleavage of the oligosaccharide
      chains from the 90-kDa glycoprotein. Antiserum did not detect a 30-kDa band in
      media from cultures of kidney, fat, heart, muscle, liver, or serum; however,
      heart and muscle did contain bands of different molecular masses that cross
      reacted with the antiserum. Multiple bands of higher molecular mass (35-40 kDa)
      were detected in the endometrial cultures from gilts on Days 0 through 10 of the
      estrous cycle. Treatment of ovariectomized gilts with estradiol-17 beta
      stimulated a similar response. During the mid- to late luteal phase of the
      estrous cycle (Days 12-18), the 30-kDa band as well as an additional 32-kDa band
      was present on Western blots. Administration of progesterone for 14 days
      stimulated the synthesis of both the 30- and 32-kDa products in ovariectomized
      gilts. However, only the pGP30 was detected on Days 12-18 of pregnancy.
      Immunocytochemical localization with antiserum to pGP30 indicated that the
      glycoprotein is present in the endometrial epithelium, with the surface
      epithelium demonstrating the strongest reaction product. Discrete changes in
      staining and cellular localization were observed during the early stages of the
      estrous cycle (Days 0-5) and the midluteal (Day 10) phase. A similar response was
      achieved with administration of steroids to ovariectomized gilts. Data indicate
      that discrete changes in epithelial synthesis of the endometrial glycoprotein
      occur at the time of conceptus trophoblastic elongation and placental attachment
      in the pig.

PMID- 8527507
TI  - Effectors of cyclic adenosine 5'-monophosphate up-regulating-oxytocin receptors
      in rabbit amnion cells: isoproterenol, parathyroid hormone-related protein, and
      potentiation by cortisol.
AB  - Forskolin (FSK; an activator of adenylyl cyclase) and cortisol synergistically
      increase the concentration of oxytocin receptors (OTRs) in rabbit amnion cells.
      The aims of this study were to characterize potential physiological regulators of
      OTR concentrations acting through adenylyl cyclase and to clarify the mechanisms
      of potentiation by cAMP and cortisol. Both isoproterenol (ISO) and parathyroid
      hormone-related protein (PTHrP) elevated amnion cell cAMP levels and OTR
      concentrations. The effects of ISO and PTHrP on OTR were potentiated by cortisol.
      Cortisol had no effect on the ability of ISO or PTHrP to stimulate adenylyl
      cyclase activity, and cAMP did not affect the number or affinity of
      glucocorticoid receptors in whole cells or in cytosol. Adenylyl cyclase
      activation, however, caused conversion of mifepristone (RU486) from a
      glucocorticoid antagonist to agonist. Thus, mifepristone elevated OTR receptor
      concentrations in the presence of FSK. In contrast, a structurally related
      glucocorticoid antagonist, onapristone (ZK98 299), was unaffected by cAMP.
      Because glucocorticoid receptors bound to mifepristone are capable of interacting
      with DNA, whereas onapristone-occupied receptors are not, we conclude that cAMP
      affects glucocoticoid receptor-DNA interactions, accounting for the synergistic
      effects of cAMP and cortisol on OTRs.

PMID- 8527508
TI  - Identification of a deoxyribonuclease I-like endonuclease in rat granulosa and
      luteal cell nuclei.
AB  - Apoptosis, a process recently implicated as the cellular mechanism underlying
      ovarian follicular atresia and luteal regression, is characterized by the
      internucleosomal degradation of DNA by a Ca2+/Mg(2+)-dependent endonuclease.
      Although hormones and growth factors have been demonstrated to modulate the DNA
      degradation associated with ovarian follicular apoptosis, the nature and identity
      of the endonuclease involved is not known. Ca2+/Mg(2+)-dependent endonuclease
      activity has a developmental pattern of expression in rat granulosa and luteal
      cell nuclei. Thus, the present study was conducted to establish the presence of
      an endonuclease in the nuclei of ovarian granulosa and luteal cells and to
      examine the biochemical properties of the enzyme relevant to apoptosis. Nuclei
      from diethyl-stilbestrol (DES)-, eCG-, and hCG-primed rat ovaries were isolated
      and exposed to Ca2+ and Mg2+ in vitro. Nuclei from rat ovaries primed with eCG
      and hCG, but not DES, substantially degraded their DNA in an apoptotic fashion,
      and this DNA degradation was Ca2+/Mg(2+)-dependent and inhibited by Zn2+. Protein
      extracts from the nuclei of DES-, eCG-, and hCG-treated rat ovaries were tested
      for endonuclease activity by a plasmid degradation assay. The extracts were found
      to contain endonuclease activity with the same developmental pattern and cation
      dependency as found in intact nuclei. These protein extracts were assessed for
      nuclease activity by zymography, and three nuclease activities were identified
      depending on the type of DNA used in the gel and the electrophoresis conditions
      used for protein separation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527509
TI  - Characterization of the oviductal sperm reservoir in cattle.
AB  - A reservoir for sperm has been found in the oviductal isthmus in several species.
      Sperm are apparently trapped in the reservoir by binding to the oviductal
      epithelium, although other factors may be involved. We hypothesized that binding
      sites for bovine sperm are limited to the isthmus and are regulated by the
      hormonal state of the cow. Ipsilateral oviducts were obtained from heifers that
      were preovulatory (in estrus), had ovulated recently (within 12 h), or were in
      diestrus (Day 10). The isthmic and the ampullar epithelium were milked out and
      incubated separately in serum-free (SFRE-199-2) medium, at 39 degrees C in 5%
      CO2. Frozen-thawed sperm from bulls were added to the epithelium and coincubated
      for 15 min. The number of spermatozoa that bound to explants was not affected by
      stage of cycle or by anatomic origin of the explants (p > 0.05). In an additional
      experiment, oviducts were infused with sperm in vivo and then prepared for
      scanning electron microscopy, which revealed that sperm were associated with
      ciliated epithelium in both the isthmus and ampulla. Thus, bovine sperm may form
      a reservoir in the isthmic end of the oviduct because it is the first oviductal
      region that they encounter.

PMID- 8527510
TI  - Opioids modulate progesterone production in prepubertal Bunaji heifers.
AB  - The opioid antagonist naloxone was administered to prepubertal heifers, and its
      effects on progesterone, cortisol, and LH secretions were studied. Pooled
      pretreatment values in peripheral plasma for progesterone averaged 0.26 +/- 0.08
      ng/ml (+/- SE), and those for cortisol averaged 13 +/- 1.2 ng/ml. Naloxone
      treatment at either 1.1 (Nal-1) or 2.0 (Nal-2) mg/kg BW significantly increased
      circulating progesterone within 15 min of i.v. injection, which was sustained for
      45 and 75 min, respectively. Maximal progesterone concentrations were 1.8 +/-
      0.16 ng/ml and 1.8 +/- 0.19 ng/ml at the low and high naloxone dosages;
      progesterone values were basal by 120 min. Naloxone caused a dose-dependent
      increase in plasma cortisol averaging 20 +/- 3.1, 28 +/- 4.2, and 49 +/- 5.7
      ng/ml in the immediate 120 min posttreatment in control, Nal-1, and Nal-2
      heifers, respectively; but naloxone injection, at either the low or the high
      dosage, had no effect on plasma LH concentration. The effect of naloxone on
      progesterone concentration was dependent on the age and body weight of the
      animal; it was first observed at 28 mo of age and between 130 and 160 kg BW. None
      of the heifers that showed transient elevations in progesterone exhibited estrous
      behavior or had a palpable CL throughout the study. These coincident transient
      increases in circulating progesterone and cortisol demonstrate that an endogenous
      inhibitory opioidergic system is involved in the control of steroid hormone
      secretion in prepubertal zebu heifers. Further, an adrenal source of this
      progesterone is indicated, but whether the progesterone participates in the
      induction of an LH increase in the prepubertal heifer is not clear.

PMID- 8527511
TI  - Activation of mammalian sperm motility by regulation of microtubule sliding via
      cyclic adenosine 5'-monophosphate-dependent phosphorylation.
AB  - Bicarbonate was found to be essential for activating live mouse sperm motility.
      The activated sperm flagella exhibited high beat frequency, high swimming
      velocity, and large principal and reverse bends. To gain further insight into the
      bicarbonate-triggered activation mechanism, the microtubule sliding
      characteristics of the activated versus the nonactivated sperm flagella were
      compared by use of demembranated sperm. We found that the effects of bicarbonate
      on live sperm were identical with the effects of cAMP on demembranated sperm both
      in microtubule sliding velocity and in sliding disintegration pattern.
      Furthermore, autoradiography revealed that the activation of mouse sperm motility
      was associated with cAMP-dependent phosphorylation of a 65-kDa flagellar protein.
      The results demonstrated that bicarbonate-triggered activation of mouse sperm
      motility was closely coupled with the regulation of microtubule sliding via cAMP
      dependent phosphorylation.

PMID- 8527512
TI  - Enucleation by centrifugation of in vitro-matured bovine oocytes for use in
      nuclear transfer.
AB  - Nuclear transfer has the potential to produce large numbers of identical progeny.
      Current limitations of the technique are associated with the use of
      micromanipulation for the demanding enucleation and reconstitution procedure.
      With the overcoming of this limitation, increased numbers of nuclear transfer
      embryos could be produced. Centrifugation of bovine oocytes at 15,000 x g for 2
      min resulted in the stratification of organelles within the cytoplasm which
      positioned the metaphase II spindle for enucleation. After removal of the zona
      pellucida with Pronase, the oocytes were centrifuged in a Percoll density
      gradient so that the oocytes were stretched apart to form cytoplasts and the
      metaphase II spindle was separated from the majority of oocytes. Enucleation by
      centrifugation efficiently produced a consistent population of enucleated
      cytoplasts from bovine in vitro-matured oocytes. The population of enucleated
      cytoplasts was enriched by exclusion of the cytoplasts that exhibited an
      extrusion cone containing metaphase II chromosomes 6 h after centrifugation. The
      enucleated oocyte cytoplasts were aggregated with blastomeres isolated from in
      vivo-collected morulae. The aggregated embryonic cells were electrofused to
      obtain nuclear transfer embryos that were placed into a sodium alginate false
      zona and were capable of cleavage and development in vitro. The development of
      nuclear transfer embryos produced through use of centrifugation and aggregation
      techniques was comparable with that of nuclear transfer embryos produced by
      micromanipulation techniques.

PMID- 8527513
TI  - Gonadotropins in lactating sows exposed to long or short days during pregnancy
      and lactation: serum concentrations and ovarian receptors.
AB  - The objective of this study was to determine the influence of day length on
      gonadotropin profiles and the expression of their ovarian receptors in lactating
      sows. Primiparous Large White gilts were exposed to either a gradual increase
      (from 12 to 16 h/day, LONG treatment, n = 13) or decrease (from 12 to 8 h/day,
      SHORT treatment, n = 12) in photoperiod during gestation. Weaning occurred at Day
      21 of lactation. All 4 sows that were submitted to the SHORT light duration and
      checked for postpartum estrus demonstrated an estrus by 10 days postwearing in
      contrast to 2 of 5 sows submitted to the LONG light duration (p < 0.05). In the
      remaining 16 sows, day length had no significant effect on the number of LH
      pulses or on mean or basal concentrations of gonadotropins (FSH and LH) or
      estradiol-17 beta measured at Day 20 of lactation. Ovarian receptors for
      gonadotropins and prolactin (PRL) and their mRNA were measured through use of
      receptor-binding and slot-blot analyses, respectively, at Day 21 of lactation in
      these 16 sows. ALONG photoperiod duration had no influence on receptor number,
      binding or affinity, but it significantly increased LH receptor mRNA levels (p <
      0.05). However, FSH receptor mRNA levels were similar in the two groups of sows.
      Plasma LH concentration was positively related to LH and FSH receptor content but
      not to their cognate mRNA levels. Plasma concentration of FSH was positively
      related to the level of its own receptor mRNA as well as to that of the PRL
      receptor mRNA. Although the LONG day length may have delayed the return to
      estrus, there was no effect on gonadotropin secretion. Our results show an effect
      of photoperiod only on the level of LH receptor mRNA. We suggest that not all
      transcripts of the LH receptor are translated and that nontranslatable mRNA
      accumulate in ovaries of sows exhibiting delayed estrus.

PMID- 8527514
TI  - Localization of insulin-like growth factor binding protein-4 expression in the
      mouse uterus during the peri-implantation period.
AB  - Previous studies have suggested a role for insulin-like growth factors (IGFs) in
      both embryo and trophoblast growth, as well as in uterine differentiation.
      Included in the IGF family are the IGF binding proteins (IGFBPs). In the current
      study we have demonstrated, by Western ligand blot of mouse uterine tissue
      extracts, a dramatic increase in IGFBP-4 at the time of embryo implantation. As
      an extension of this finding, we used in situ hybridization to examine the
      ontogeny and anatomical localization of IGFBP-4 mRNA in the mouse uterus during
      the peri-implantation period. On gestational Day 2, while the embryos are still
      in the oviduct, no uterine IGFBP-4 mRNA signal was observed. However, on
      gestational Day 4, when the embryos are free in the uterine lumen, IGFBP-4 mRNA
      was present in the uterine stroma underlying the luminal epithelium. By
      gestational Day 6, approximately 24 h after implantation, a IGFBP-4 mRNA signal
      was intense at each implantation site and extended throughout the decidua. A
      signal was absent in the uterine tissue between implantation sites. By
      gestational Day 8, the IGFBP-4 mRNA signal was reduced and confined to the stroma
      nearest the myometrium. The specific anatomical and temporal nature of the IGFBP
      4 mRNA expression suggests a physiologic role for this binding protein in the
      implantation process.

PMID- 8527515
TI  - Modulation of cholesteryl ester hydrolase messenger ribonucleic acid levels,
      protein levels, and activity in the rat corpus luteum.
AB  - Previous studies have shown that the induction of functional luteolysis (loss of
      progesterone production) with either prostaglandin F2 alpha (PGF2 alpha)
      treatment or hypophysectomy (APX) diminished neutral cholesteryl ester hydrolase
      (CEH) activity in the corpus luteum (CL) and that prolactin (PRL) replacement of
      APX animals prevented luteolysis and maintained CEH activity at control levels.
      More recent studies have shown that CEH is the same protein as hormone-sensitive
      lipase (HSL) and that CEH/HSL activity may be regulated by phosphorylation.
      However, the possibility that CEH/HSL activity may be under transcriptional
      and/or translation control has not been excluded. Therefore, in the present study
      we examined whether PGF2 alpha treatment, APX, or inhibition of PRL secretion by
      bromocryptine (BrC) treatment modulated CEH/HSL mRNA and/or protein levels in a
      coordinate fashion with CEH activity. Furthermore, we examined whether CEH/HSL
      mRNA and/or protein levels changed after luteinization of the ovary and after
      natural functional regression. PGF2 alpha treatment and APX significantly reduced
      CEH activity; and PGF2 alpha treatment, APX, and BrC treatment significantly
      reduced CEH/HSL protein and mRNA levels. PRL replacement after APX substantially
      blocked the reductions in CEH activity, CEH/HSL protein, and CEH/HSL mRNA levels.
      PRL replacement during BrC treatment significantly inhibited the reductions in
      CEH/HSL protein and mRNA levels. CEH/HSL mRNA levels increased twofold after
      luteinization. Whereas CEH/HSL mRNA levels remained elevated after natural luteal
      regression, CEH/HSL protein significantly decreased. In summary, the luteolytic
      actions of PGF2 alpha, APX, and BrC resulted in coordinate reductions in luteal
      CEH activity, protein levels, and mRNA levels; PRL replacement significantly
      reversed the luteolytic effects of APX and BrC; natural luteal regression
      resulted in a reduction in CEH/HSL protein without a concomitant reduction in
      CEH/HSL mRNA. These results suggest that ovarian CEH activity is controlled at
      the level of both transcription and translation, and that PRL is important for
      continued CEH/HSL mRNA transcription in the CL.

PMID- 8527516
TI  - Beta 2-integrin (CD11b/CD18) is the primary adhesive glycoprotein complex
      involved in neutrophil-mediated immune injury to human sperm.
AB  - The pathogenesis of antisperm antibody (ASA)-mediated infertility is postulated
      to be related in part to complement (C)-dependent neutrophil-mediated injury to
      sperm in the female genital tract. We have reported that sperm-bound IgG
      activated human C and deposited C3 fragments on motile sperm. We also
      demonstrated that IgG and C3-bound motile sperm adhered to human neutrophils in
      vitro, and that this adhesion potentiated the localized release of oxygen
      radicals at the site of neutrophil/sperm membrane contact. The goal of the
      present study was to identify the neutrophil surface receptor(s) involved in
      neutrophil/sperm adhesion and to evaluate their relevance to the pathogenesis of
      neutrophil-mediated immune injury to sperm. Neutrophils were coincubated with
      motile sperm in the presence of C-fixing ASA+ sera or control sera. After defined
      incubation periods, the following neutrophil variables were evaluated: 1) surface
      expression of Fc (Fc gamma RII and Fc gamma RIII) and C receptors (CR1[CD35], CR3
      [CD11b/CD18], and CR4 [CD11c/CD18]) by flow cytometry, 2) neutrophil aggregation
      by flow cytometry, 3) tyrosine phosphorylation of neutrophil proteins by flow
      cytometry, and 4) the immune adherence and ingestion of sperm by light and
      scanning electron microscopy (SEM). The functionality of adhesion receptors was
      studied by use of a panel of anti-leukocyte monoclonal antibodies (mAbs) for
      their ability to block neutrophil/sperm adhesion and neutrophil aggregation. Only
      the incubation of neutrophils and sperm in the presence of C-fixing ASA+ sera
      resulted in marked (> 70%) sperm binding to neutrophils. Consistent with this
      pattern, a significant (p < 0.0001) increase in surface expression of neutrophil
      CD11b and neutrophil aggregation was evident. According to SEM, most of the sperm
      were linked to the neutrophil by the acrosomal region of sperm head. Maximum
      expression of CD11b antigen was obtained when neutrophils were coincubated with
      sperm in the presence of C-fixing ASA+ sera. CD11b up-regulation correlated with
      a significant (p < 0.05) increase in tyrosine phosphorylation of neutrophil
      proteins during sperm phagocytosis. Only the combination of mAbs directed to the
      beta 2-integrin, CD11b (D12/SHCL-3), or CD18 (MHM23) subunits maximally inhibited
      ASA- and C-mediated sperm adhesion to neutrophils (by 70%) or sperm phagocytosis
      (by 75%), as well as neutrophil aggregation (by 96%). These findings strongly
      implicate the CD11b/CD18 glycoprotein complex (CR3) in the adhesive events
      involved in ASA- and C-mediated immune destruction of motile sperm by
      neutrophils.

PMID- 8527517
TI  - Studies on the role of plasminogen activators and plasminogen activator inhibitor
      type-1 in rat corpus luteum of pregnancy.
AB  - Luteal development and demise are characterized by substantial tissue destruction
      and remodeling, which is associated with local production of plasminogen
      activation. Recently we reported involvement of tissue-type plasminogen activator
      (tPA) in luteolysis in rhesus monkeys. In this study, we further investigated
      changes in expression of both tPA and urokinase-type plasminogen activator (uPA)
      activity during various developmental stages of rat corpus luteum (CL) of
      pregnancy and their possible physiological roles in luteolysis. Rat CL or
      dispersed luteal cells in vitro are capable of producing both tPA and uPA, and a
      plasminogen activator inhibitor type-1, in a stage-dependent manner. However,
      only tPA activity significantly increases in late phases of CL development.
      Furthermore, the increase in tPA activity in the CL is well correlated with a
      sharp decrease in luteal progesterone production. Addition of exogenous tPA to
      the luteal culture considerably decreases progesterone production. In contrast,
      immunoneutralization of endogenously produced tPA activity by inclusion of tPA
      monoclonal antibody in the culture results in a significant increase in luteal
      progesterone production. It is therefore suggested that tPA may also be involved
      in suppression of rat luteal function. This hypothesis is further supported by
      the findings that interferon-gamma significantly inhibits luteal basal and hCG
      stimulated progesterone production and also stimulates basal and hCG-induced tPA
      activity. On the basis of the data provided in this study and similar findings in
      monkeys, we conclude that endogenously produced tPA in late phase of CL
      development may regulate luteal regression through local autocrine or paracrine
      action.

PMID- 8527518
TI  - Expression of SQ10 (a preprorelaxin-like gene) in the pregnant rabbit placenta
      and uterus.
AB  - A Northern blot containing poly(A)+ RNA isolated from pregnant rabbit placenta,
      uterus, ovary, mammary gland, psoas muscle, and intestine was hybridized with an
      oligonucleotide probe to porcine preprorelaxin. Only the placenta and uterus
      exhibited high levels of a 1-kb mRNA that hybridized to the probe. Porcine
      preprorelaxin primers were used to generate and amplify cDNAs from placental and
      uterine poly(A)+ RNA. Southern blot analysis of the placental and uterine cDNAs
      each revealed a single PCR product that hybridized with the porcine relaxin
      probe. The sequence of the cDNAs exhibited 100% identity with SQ10, a
      preprorelaxin-like gene identified in rabbit tracheobronchial epithelial cells.
      Identical results were obtained with primers specific for SQ10. SQ10 is expressed
      in tracheobronchial epithelial cells during abnormal conditions, such as
      mechanical or toxic injury. The protein is believed to have a role in tracheal
      epithelial cell differentiation and transformation that occurs under the above
      conditions. This work shows, for the first time, the presence of high levels of
      message for SQ10 in normal reproductive tissues. The expression of SQ10 in the
      uterus and placenta may suggest an important role in cell differentiation and
      transformation that occurs in these tissues during pregnancy.

PMID- 8527519
TI  - Abdominal position of the rat testis is associated with high level of lipid
      peroxidation.
AB  - Experimental cryptorchidism in the adult rat induces lipid peroxidation as a sign
      of oxidative stress. To further elucidate the role of free radicals and
      antioxidant enzymes in the degeneration of testis in cryptorchidism, we first
      studied testes of untreated rats before and after the normal testicular descent.
      In the second experiment, primary unilateral cryptorchidism was induced by
      surgically attaching one testis of each rat to the abdomen before testicular
      descent. The level of lipid peroxidation was detected by formation of fluorescent
      chromolipids and diene conjugates. At the age of testicular descent (18-21 days),
      the level of fluorescent chromolipids dropped to one third (p < 0.05).
      Correspondingly, the level of diene conjugates was 69% (p < 0.05) higher at 18
      than at 30 days of age. The antioxidant enzyme activities did not change at the
      time of testicular descent. Primary unilateral cryptorchidism was induced at the
      age of 13 days. At 25 or 35 days of age, the level of diene conjugates was higher
      in the cryptorchid testes than in the contralateral scrotal testes (+39%, p <
      0.01, and +51%, p < 0.001, respectively). In the abdominal testes, the mRNA of
      CuZn superoxide dismutase (SOD) was increased by 69% (p < 0.05) at 25 days,
      whereas by 35 days of age enzymatic CuZn SOD activity was slightly decreased and
      catalase activity increased. The present results show that the abdominal position
      of the testis, either before normal testicular descent or in experimental
      cryptorchidism, is associated with a high level of lipid peroxidation. The data
      provide evidence that increased production of reactive oxygen species could
      contribute to degeneration of the cryptorchid testis. The oxidative testis. The
      oxidative stress in the cryptorchid testis is not explained by inactivation of
      antioxidant enzymes.

PMID- 8527520
TI  - Demonstration of tissue-specific promoters in nonprimate species that express
      aromatase P450 in placentae.
AB  - Conversion of androgens to estrogens is catalyzed by aromatase P450 (P450arom;
      the product of the CYP19 gene). Regulation of tissue-specific expression of
      P450arom in humans is due, in part, to alternative transcriptional start sites
      that arise as a consequence of the use of granulosa cells and placental tissue
      from cows, horses, and pigs (ungulates) in order to determine whether these
      species, like the human, utilize tissue-specific promoters to drive P450arom
      expression. The majority of transcripts in the placenta have 5'-termini that
      differ from those in the ovary upstream of a common site of divergence,
      indicative of a splice junction. The use of tissue-specific promoters by the
      bovine CYP19 gene would produce these results, as it does in the case of the
      human CYP19 gene. A bovine genomic library was then screened with probes that
      hybridize to ovary- or placenta-specific transcripts. Two clones of approximately
      15 kb each in length were isolated; one hybridized with the ovary-specific
      sequence and the other hybridized with the placenta-specific sequence. Whereas
      the former sequence was contiguous with the downstream sequence containing the
      translational start site, the latter was identical only with the sequence of the
      placental transcripts upstream of the putative splice junction, indicating that
      this was the distal sequence. Bovine and human ovary-specific genomic sequences
      share 77% bp identity, while bovine and human placenta-specific sequences
      demonstrated only 39% bp identity. These results mirror those obtained in
      comparisons of human, bovine, equine, and porcine ovarian and placental RACE cDNA
      5'-termini.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527521
TI  - Four-day-old bovine corpus luteum: progesterone production and identification of
      matrix metalloproteinase activity in vitro.
AB  - Little is known about matrix metalloproteinases (MMPs), enzymes that are required
      for the structural remodeling and angiogenesis that occur in the corpus luteum
      (CL) during the first several days postovulation. In fact, little attention has
      focused on early CL function including the regulation of progesterone (P4)
      production. Thus, the objective of the present study was 1) to investigate the
      effects of insulin, LH, and dibutyryl cAMP on P4 production and cell numbers and
      2) to identify MMPs in the 4-day-old CL, with use of a defined culture system.
      Cultures were seeded with either 1 x 10(6) or 0.5 x 10(6) cells. All cultures
      containing insulin had higher P4 levels and cell numbers (p < 0.05) than those
      without. In cultures containing insulin, basal P4 levels were high throughout the
      culture period. Furthermore, neither LH nor dibutyryl cAMP stimulated P4
      production (p > 0.05) at a seeding density of 1 x 10(6), whereas they stimulated
      P4 production (p < 0.05) at a seeding density of 0.5 x 10(6) on Days 6 and 8 of
      culture. In conditioned medium of control cultures seeded with 0.5 x 10(6) cells,
      substrate gel electrophoresis (zymography) showed two intense bands that migrated
      at M(r) approximately 97,000 and approximately 65,000-64,000, while two weaker
      ones migrated at M(r) approximately 88,000 and approximately 64,000-63,000. The
      molecular weights of the M(r) approximately 97,000 and approximately 88,000
      species were consistent with MMP-9 family members, while the molecular weights of
      the M(r) approximately 65,000-64,000 and approximately 64,000-63,000 species were
      consistent with MMP-2 family members.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527522
TI  - Spontaneous recrudescence of spermatogenesis in the photoinhibited male
      Djungarian hamster, Phodopus sungorus.
AB  - Photosensitive rodents exposed to inhibitory short photoperiods become
      insensitive to this environmental factor after prolonged exposure. During the
      following process of spontaneous recrudescence, the animals that have adapted to
      the winter season show a return of all seasonal parameters. In the Djungarian
      hamster, obvious photoperiod-dependent changes are reinitiation of the
      reproductive organs, a 20-30% increase in body weight, and a moult from whitish
      fur into brown summer fur. This study was designed to analyze the morphological
      and endocrinological changes occurring during spontaneous testicular
      recrudescence in male Djungarian hamsters under prolonged short photoperiods. Two
      experiments were performed 1) to analyze the time-dependent changes in groups of
      hamsters exposed to short photoperiods and 2) to observe testicular and humoral
      changes in individual animals during spontaneous recrudescence. Regrowth of the
      testes and seminal vesicles did not begin before Week 18 in short photoperiods.
      While serum testosterone did not increase before Week 24, serum FSH had already
      returned to normal values from Week 18 onwards. Individual analysis by enzyme
      histochemistry revealed that 3 beta-hydroxysteroid-dehydrogenase activity in
      Leydig cells was not restored before testicular weights of more than 400 mg were
      observed and the first wave of spermatogenesis had reached the stage of elongated
      spermatids. This indicates that the testicular testosterone production was low
      until a status of testicular recrudescence had been achieved, at which point the
      testis showed complete qualitative spermatogenesis and a restoration of the
      Sertoli cell actin filaments. These data suggest that the process of early
      spontaneous recrudescence in male Djungarian hamsters appears to be initiated by
      the restoration of serum FSH rather than by testosterone.

PMID- 8527523
TI  - Effect of photoperiod before and after birth on puberty in ewe lambs.
AB  - Previous studies have shown that exposure to long days followed by short days
      after 12 wk of age advances the onset of puberty in ewe lambs. The aim of this
      experiment was to determine whether or not puberty would be advanced by exposure
      of lambs to such a photoperiodic regime when the long days were given before
      birth and the short days immediately after birth. Ewes kept in natural
      photoperiod (NP) were housed on January 15 and allocated at random to one of four
      treatments: 1) NP/NP, natural photoperiod before and after parturition (n = 26);
      2) SD/SD, short days (SD; 9L:15D) before and after parturition (n = 27); 3)
      LD/NP, long days (LD; 18L:6D) before parturition and NP after parturition (n =
      27); and 4) LD/SD, LD before parturition and SD after parturition (n = 26). Mean
      (+/- SEM) birth date for all lambs was March 20 +/- 1 day, and the number of days
      of exposure to long and short days prior to parturition was 64 +/- 2 and 67 +/- 2
      days, respectively. From ewes on the four treatments, 24, 20, 14, and 16 female
      lambs, respectively, were reared. Lambs were weighed at birth and at weekly
      intervals after weaning. Reproductive activity in ewe lambs was assessed from
      serum progesterone concentrations in blood samples collected twice weekly from
      August 1 until puberty was reached or the experiment terminated on November 17
      (34 wk after birth).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527524
TI  - Follicular and luteal progesterone play different roles synchronizing pituitary
      and ovarian events in the 4-day cyclic rat.
AB  - Administration of 4 mg of the antiprogestagen RU486 to 4-day cyclic rats during
      proestrus induced a 1-day shortening of the ovarian cycle, a reduction in
      ovulatory rate that was reversed by an injection of exogenous human (h)FSH in the
      evening of proestrus, and the absence of the LH-inhibiting effect of exogenous
      estradiol resulting in a 24-h advancement of the preovulatory LH surge. These
      effects were not present when RU486 was injected during estrus. RU486 injected
      during either proestrus or estrus increased serum levels of LH and estradiol-17
      beta in diestrus and reduced the magnitude of the preovulatory surge of
      gonadotropins. Only rats treated with RU486 during estrus showed increased
      follicular size and acceleration of oocyte maturation on proestrous afternoon.
      These results demonstrate that in 4-day cyclic rats receiving an injection of
      RU486 during proestrus, the low ovulatory rate is a consequence of a reduced
      secondary FSH surge-induced follicular recruitment in the afternoon of estrus and
      that the shortening of the estrous cycle is the result of an advanced
      desensitization to the negative feedback of estradiol on LH secretion.
      Furthermore, since the administration of RU486 during proestrus blocks both
      follicular and luteal progesterone actions whereas injection during estrus blocks
      only luteal progesterone actions, we suggest that, in 4-day cyclic rats, the
      actions of progesterone during diestrus retard maturation of follicles via the
      lowering of serum LH concentrations and that the actions of progesterone in
      proestrous evening delay the desensitization to the negative estrogen feedback on
      LH secretion.

PMID- 8527525
TI  - Aberrant hormone balance in fetal autoimmune NZB/W mice following prenatal
      exposure to testosterone excess or the androgen blocker flutamide.
AB  - F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are
      hormone-sensitive models of the human disease systemic lupus erythematosus. In
      this study, NZB/W fetuses produced by pregnant NZB mice were compared with F1
      C57BL/6 x DBA/2 (C57/DBA2) hybrid fetuses produced by nonautoimmune C57BL/6
      females. Dams of both strains were treated with testosterone or the androgen
      blocker flutamide to alter the hormonal environment in late gestation. Hormonal
      changes in male fetuses carried by treated dams were of interest because hormonal
      manipulation using either testosterone or flutamide has been shown to increase
      longevity in male NZB/W offspring. Testosterone-implanted NZB dams developed the
      expected elevations in circulating maternal testosterone, whereas C57BL/6 dams
      treated with either testosterone or flutamide had elevated maternal serum
      testosterone concentrations. The treatment-induced changes in circulating
      testosterone in NZB dams and C57BL/6 dams were not reflected in serum from 18-day
      NZB/W or C57/DBA2 fetuses. Male NZB/W offspring from untreated control NZB dams
      had unexpectedly high levels of serum estradiol and alpha fetoprotein and
      relatively low extractable testicular testosterone, compared with nonautoimmune
      male control fetuses. Maternal testosterone treatments produced a significant
      decrease in serum estradiol in NZB/W male fetuses, and placental testosterone
      content was also reduced. Our findings suggest that placental androgen control is
      regulated differently in the autoimmune NZB-NZB/W vs. the nonautoimmune C57BL/6
      C57/DBA2 maternal-placental-fetal unit.

PMID- 8527526
TI  - Free estradiol in serum and brain uptake of estradiol during fetal and neonatal
      sexual differentiation in female rats.
AB  - Circulating estradiol is assumed not to contribute to sexual differentiation of
      the brain or other estrogen target tissues. The only estradiol available for
      binding to estrogen receptors is thought to be produced within brain cells by the
      aromatization of testosterone to estradiol as part of the action of androgen in
      the brain. However, we report that the concentration of free, biologically active
      serum estradiol (the concentration not bound to plasma proteins) was 0.54-2.17
      pg/ml during the fetal and early neonatal period of sexual differentiation. These
      values were within the same concentration range for free estradiol observed in
      adult female rats throughout the estrous cycle (diestrus = 0.53 pg/ml; proestrus
      = 2.26 pg/ml), and estradiol clearly has physiological effects during diestrus as
      well as proestrus in adult females. When a stable, physiological blood
      concentration of [3H]estradiol of 49 pg/ml total (0.61 pg/ml free) was achieved
      with Silastic capsules in 2-day-old female pups, [3H]estradiol was recovered
      specifically bound to brain cell nuclei at approximately 2.7 fmol per pup brain
      or 12.4 fmol/mg DNA. The finding of brain uptake of circulating estradiol is
      contrary to current hypotheses. These findings suggest that estradiol in the
      fetal and neonatal circulation may be able to interact with testosterone and its
      metabolites to regulate sexual differentiation of the brain and other estrogen
      target tissues.

PMID- 8527527
TI  - Patterns of ovarian cell proliferation in rats during the embryonic period and
      the first three weeks postpartum.
AB  - The purpose of this study was to characterize the patterns of ovarian cell
      proliferation during the earliest stages of folliculogenesis, which occur in the
      embryonic period and the first weeks postpartum in rats. Rats were given
      continuous infusions of [3H]thymidine (3H-TdR) or bromodeoxyuridine (BrdU), and
      cells that were synthesizing DNA were visualized by autoradiography or
      immunohistochemistry. There were dramatic changes in the patterns of cell
      proliferation during the period studied. Mesenchymal cells proliferated
      extensively in the embryonic and neonatal ovary, but their growth fraction
      declined precipitously as follicles formed. Epithelial cells in the medulla of
      the ovary left the cell cycle at about embryonic Day 12, then resumed
      proliferation as soon as they were incorporated into follicles just after birth.
      Epithelial cells towards the cortex of the organ continued to proliferate until
      late in the embryonic period; they apparently became quiescent around the time of
      birth, and incorporation into follicles did not release them from their quiescent
      state. After the follicles had formed, patterns of cell proliferation continued
      to change. At 5 days postpartum, approximately 36% of the smallest follicles (1-8
      granulosa cells in cross section) had at least 1 granulosa cell that was labeled
      following a 24-h infusion of 3H-TdR; by Day 20 only 14% of these follicles were
      labeled, and by Day 30 only 4.4% were labeled.

PMID- 8527528
TI  - Cell-specific organization of the 5S ribosomal RNA gene cluster DNA loop domains
      in spermatozoa and somatic cells.
AB  - DNA in eucaryotic cells is organized into loop domains, ranging in size from 25
      to 100 kb, that are attached at their bases to the structural component of the
      nucleus termed the nuclear matrix. These DNA loop domains have been shown to be
      important in the regulation of both DNA replication and RNA transcription. In
      this study we have compared the structural organization of the DNA loop domains
      of the 5S rRNA gene cluster in sperm, liver, and brain nuclei in the Syrian
      golden hamster. The individual loop domains were visualized by fluorescent in
      situ hybridization to protamine (sperm)- and histone (somatic)-depleted nuclei,
      termed nuclear matrix halo preparations. We found that in sperm nuclei, the 5S
      rRNA gene cluster was organized into three small loop domains that were
      approximately 48 kb each. In both types of somatic cell nuclei examined, the 5S
      rRNA gene cluster was organized into a single, much larger loop domain that was
      up to 480 kb in length. The data suggest that at least some of the compaction
      that sperm DNA undergoes during spermiogenesis is mediated by the nuclear matrix
      independent of protamine binding. Additionally, this sperm-specific DNA
      organization may be involved in the specific patterns of DNA replication and
      transcription of the paternal genome in the embryo.

PMID- 8527529
TI  - Antisense oligonucleotide down-regulation of E-cadherin in the yolk sac and
      cranial neural tube malformations.
AB  - The cadherins are a family of calcium-dependent cell adhesion molecules that are
      regulated both spatially and temporally during development. Epithelial cadherin
      (E-cadherin) is present in epithelial cells in both the embryo and yolk sac
      during organogenesis. The consequences of disrupting the expression of E-cadherin
      at this stage of development are poorly understood. We report here our studies on
      the effects of antisense oligonucleotides on E-cadherin in the rat whole embryo
      culture system. Four 18-base single strand phosphorothioate oligodeoxynucleotides
      (AS-oligos), complementary to various regions of the mouse E-cadherin cDNA
      sequence, were dissolved in saline and injected into the amniotic cavities of 5-7
      somite rat embryos; a sense (S-oligo) to oligo-1, an 18-base random sequence
      oligo (C-oligo), and PBS were used as controls. Embryos were cultured for up to
      45 h; embryo morphology and the relative concentrations of E-cadherin protein
      were examined. All six oligonucleotides (AS-oligos and control oligos) induced
      malformations when amounts ranging from 25 to 50 pmol of oligonucleotide were
      injected per embryo. The malformations induced by all the oligos included
      craniofacial hypoplasia, an enlarged pericardium, twisted spinal cord, swelling
      of the rhombencephalon, and underdeveloped forelimb. Injection of AS-oligo-1, a
      sequence starting at the tenth base downstream from the translation initiation
      codon (ATG), resulted in malformed embryos with a high incidence of cranial
      neural tube malformations. The effects of AS-oligo-1 on the relative abundance of
      E- and neural (N)-cadherin proteins were examined by Western blot analysis. In
      the AS-oligo-1-exposed malformed embryos, the relative abundance of E- and N
      cadherin proteins was not altered up to 24 h after injection; E- and N-cadherin
      concentrations in the embryo were decreased at 45 h postinjection. In contrast,
      the relative abundance of the E-cadherin protein in the yolk sac was reduced at 1
      2 h after injection of AS oligo-1 and returned to control levels by 4 h. S-oligo
      1 did not induce any change in the relative abundance of E- or N-cadherins. Thus,
      there was a tissue-specific and temporary "knockdown" of E-cadherin expression in
      the yolk sac of embryos exposed to antisense (AS-oligo-1); the down-regulation of
      yolk sac E-cadherin appears to lead to the induction of neural tube defects in
      the embryo. The exposure of whole embryos in culture to antisense
      oligonucleotides provides a model system in which the roles of developmentally
      important molecules and their spatial and temporal contributions to embryogenesis
      can be elucidated.

PMID- 8527530
TI  - Effect of cryoprotectant solutes on water permeability of human spermatozoa.
AB  - Osmotic permeability characteristics and the effects of cryoprotectants are
      important determinants of recovery and function of spermatozoa after
      cryopreservation. The primary purpose of this study was to determine the osmotic
      permeability parameters of human spermatozoa in the presence of cryoprotectants.
      A series of experiments was done to: 1) validate the use of an electronic
      particle counter for determining both static and kinetic changes in sperm cell
      volume; 2) determine the permeability of the cells to various cryoprotectants;
      and 3) test the hypothesis that human sperm water permeability is affected by the
      presence of cryoprotectant solutes. The isosmotic volume of human sperm was 28.2
      +/- 0.2 microns3 (mean +/- SEM), 29.0 +/- 0.3 microns3, and 28.2 +/- 0.4 microns3
      at 22, 11, and 0 degrees C, respectively, measured at 285 mOsm/kg via an
      electronic particle counter. The osmotically inactive fraction of human sperm was
      determined from Boyle van't Hoff (BVH) plots of samples exposed to four different
      osmolalities (900, 600, 285, and 145 mOsm/kg). Over this range, cells behaved as
      linear osmometers with osmotically inactive cell percentages at 22, 11, and 0
      degrees C of 50 +/- 1%, 41 +/- 2%, and 52 +/- 3%, respectively. Permeability of
      human sperm to water was determined from the kinetics of volume change in a
      hyposmotic solution (145 mOsm/kg) at the three experimental temperatures. The
      hydraulic conductivity (Lp) was 1.84 +/- 0.06 microns.min-1.atm-1, 1.45 +/- 0.04
      microns.min-1.atm-1, and 1.14 +/- 0.07 microns.min-1.atm-1 at 22, 11, and 0
      degrees C, respectively, yielding an Arrhenius activation energy (Ea) of 3.48
      kcal/mol. These biophysical characteristics of human spermatozoa are consistent
      with findings in previous reports, validating the use of an electronic particle
      counter for determining osmotic permeability parameters of human sperm. This
      validated system was then used to investigate the permeability of human sperm to
      four different cryoprotectant solutes, i.e., glycerol (Gly), dimethylsulfoxide
      (DMSO), propylene glycol (PG), and ethylene glycol (EG), and their effects on
      water permeability. A preloaded, osmotically equilibrated cell suspension was
      returned to an isosmotic medium while cell volume was measured over time. A Kedem
      Katchalsky model was used to determine the permeability of the cells to each
      solute and the resulting water permeability. The permeabilities of human sperm at
      22 degrees C to Gly, DMSO, PG, and EG were 2.07 +/- 0.13 x 10(-3) cm/min, 0.80 +/
      0.02 x 10(-3) cm/min, 2.3 +/- 0.1 x 10(-3) cm/min, and 7.94 +/- 0.67 x 10(-3)
      cm/min, respectively. The resulting Lp values at 22 degrees C were reduced to
      0.77 +/- 0.08 micron.min-1.atm-1, 0.84 +/- 0.07 micron.min-1.atm-1, 1.23 +/- 0.09
      microns.min-1.atm-1, and 0.74 +/- 0.06 micron.min-1.atm-1, respectively. These
      data support the hypothesis that low-molecular-weight, nonionic cryoprotectant
      solutes affect (decrease) human sperm water permeability.

PMID- 8527531
TI  - Activation of the baboon fetal pituitary-adrenocortical axis at midgestation by
      estrogen: responsivity of the fetal adrenal gland to adrenocorticotropic hormone
      in vitro.
AB  - We have previously demonstrated that increased expression of fetal pituitary
      proopiomelanocortin mRNA and the induction of enzymes catalyzing fetal adrenal
      cortisol formation at term are regulated by estrogen-induced changes in placental
      oxidation of maternal cortisol to cortisone. To test the hypothesis that
      induction of fetal pituitary adrenocorticotropic hormone (ACTH) production by
      estrogen-induced changes in placental cortisol oxidation results in increased
      responsivity of the fetal adrenal gland to ACTH, in the present study we compared
      fetal adrenal sensitivity to ACTH in vitro at midgestation in untreated controls
      and in animals treated at this time in gestation with estrogen. Fetal adrenals
      were obtained on Day 100 (n = 7) and Day 165 (n = 5; term = Day 184) from
      untreated baboons and on Day 100 following maternal treatment with estradiol
      (s.c.; Days 70-100; n = 10) or androgen precursor (n = 3). Adrenal slices (15-25
      mg) were perifused (100 microliters/min; 37 degrees C) with Medium 199 (no phenol
      red); media were collected at 10-min intervals and assayed for cortisol and
      dehydroepiandrosterone. Secretion of cortisol and dehydroepiandrosterone reached
      equilibrium after 140 min of perifusion; therefore, basal release was calculated
      as the mean steroid concentrations during 190-240 min. Adrenal slices were then
      perifused for 20 min with saline or ACTH at 240 (0.001 nmol), 370 (0.01 nmol),
      and 490 (0.1 nmol) min, and an overall average cortisol/dehydroepiandrosterone
      secretion rate (pg/min/mg) between 240-600 min was calculated.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8527532
TI  - Infections of the eye.

PMID- 8527533
TI  - Nosocomial tuberculosis: new progress in control and prevention.
AB  - Nosocomial cases of tuberculosis have affected both health care workers and
      hospitalized patients, and each group has transmitted the infection to the other.
      This situation has been exacerbated by increases in the number of patients
      concurrently infected with human immunodeficiency virus and organisms resistant
      to multiple drugs; by inadequate implementation of procedures for the
      recognition, isolation, and treatment of patients with tuberculosis in health
      care and correctional facilities; and by a lack of practical engineering
      interventions for the control of airborne transmission. Epidemics at several
      hospitals have been controlled by the implementation of multiple measures listed
      in recent federal guidelines. Rapid recognition of cases and their effective
      isolation should be a priority at public hospitals, which can least afford the
      expensive engineering changes and personal respirators that are now mandated.
      Lacking are data on engineering controls (especially for retrofitting of existing
      facilities) and requirements for mask use that are both effective and financially
      practical. If relevant programs are to be developed, new methods are needed for
      the direct measurement of airborne transmission of tuberculosis. Fortunately, new
      federal guidelines allow individual hospitals and health care systems the
      flexibility to assess likely risk and to act in accordance with their findings to
      develop system-wide control programs.

PMID- 8527534
TI  - Short-course doxycycline treatment versus conventional tetracycline therapy for
      scrub typhus: a multicenter randomized trial.
AB  - To assess the clinical efficacy of short-course doxycycline in the treatment of
      scrub typhus, we compared conventional 7-day tetracycline therapy with 3-day
      doxycycline therapy in 116 patients. Patients were randomized to receive either
      tetracycline (500 mg four times daily; n = 50) or doxycycline (100 mg twice
      daily; n = 66) and were followed for 4 weeks after the completion of treatment.
      The cure rate was 100% in the tetracycline group and 93.9% in the doxycycline
      group (P > .05). The two groups did not differ significantly in terms of the
      interval required for defervescence or for the alleviation of symptoms. There
      were no relapses in either group. These data suggest that 3-day doxycycline
      therapy is as effective as conventional 7-day tetracycline therapy for the cure
      of scrub typhus and the prevention of relapses.

PMID- 8527535
TI  - Transmission of Toxoplasma gondii infection by liver transplantation.
AB  - Toxoplasmosis is an important disease in immunocompromised hosts, particularly in
      patients with AIDS and in heart transplant recipients. Infection with Toxoplasma
      is less commonly seen in recipients of other solid organ transplants. We report a
      case of fulminant disseminated infection with Toxoplasma after liver
      transplantation. Despite numerous diagnostic studies including open lung biopsy,
      toxoplasmosis was diagnosed only at the time of autopsy and involved the brain,
      spinal cord, pituitary gland, lungs, and heart. Toxoplasmosis should be
      considered in the differential diagnosis of multiorgan failure in the early
      period after liver transplantation. If mismatched serologies could be identified
      then clinical suspicion might be higher and prophylactic or empirical therapy
      could be instituted. The United Network for Organ Sharing (Richmond, VA) should
      consider including serology for Toxoplasma in the testing of donors.

PMID- 8527536
TI  - Enterococcal arthritis: case report and review.
AB  - We report a case of septic arthritis due to Enterococcus species and review 18
      additional cases reported in the literature from 1966 through 1993 for which
      clinical or treatment data were available. In 11 of the 19 cases, prosthetic
      joints were affected (9 knees, 2 hips) and in 8 cases, native joints were
      affected. Of those patients with prosthetic joint infections, 6 had preexisting
      osteoarthritis and 3 had rheumatoid arthritis; only one patient with native joint
      infection had a recognized (although unspecified), preexisting joint abnormality.
      Pain, fever (temperature, > 37 degrees C), and tenderness were the most common
      clinical findings in patients with native joint infections. The microbiological
      diagnosis was made by culture of synovial fluid or synovial tissue (16 of 19),
      blood (1 of 19), or an unstated specimen (2 of 19). Polymicrobial infection was
      present in 6 (32%) of 19 patients. Of fourteen patients treated with either a
      parenteral penicillin (11 of 19) or a glycopeptide (3 of 19), 11 made an
      uncomplicated recovery. An aminoglycoside was also used to treat 7 of these 14
      patients (4 of these 7 had prosthetic joints). All 11 prosthetic joint infections
      were ultimately clinically cured; for most of these patients, the original
      prosthesis was removed. For two patients with native joint infections, amputation
      of the infected limb was necessary to cure the infection.

PMID- 8527537
TI  - Salmonella mycotic aneurysm of the aortic arch: case report and review.
AB  - Salmonella mycotic aneurysms of the thoracic aorta are exceedingly rare. We
      describe what we believe is only the third reported case involving the aortic
      arch. The patient was treated with surgical intervention and a prolonged course
      of antibiotics, which resulted in long-term survival. We review 13 previously
      reported cases of salmonella mycotic aneurysms of the thoracic aorta. The overall
      outcome was abysmal, with 10 of 13 patients dying within 1 month after the
      diagnosis was made. We discuss the pathogenesis, clinical presentation,
      diagnostic approach, and management (including surgical intervention and duration
      of antibiotic therapy) of this condition on the basis of the findings in these
      cases.

PMID- 8527538
TI  - Aspergillus sinusitis in patients with AIDS: report of three cases and review.
AB  - Invasive aspergillosis is an uncommon but increasingly reported complication of
      AIDS. Sinusitis, usually bacterial in etiology, is frequently seen among human
      immunodeficiency virus (HIV)-infected patients. We discuss the cases of three
      patients with AIDS and invasive aspergillus sinusitis seen at our institutions
      and those of 15 patients who are described in the literature. Seven of the 18 had
      brain involvement, 3 had orbital involvement, and 7 had mastoid or other bony
      disease. Three had evidence of concomitant invasive pulmonary aspergillosis. Of
      15 patients with evaluable histories, 11 had recognized risks for invasive
      aspergillosis; 6 had previous sinusitis, otitis, or polyposis; and 11 had prior
      conditions indicative of advanced HIV-related disease. Despite aggressive
      surgical intervention and systemic antifungal therapy, nearly all patients died
      as a result of aspergillosis.

PMID- 8527539
TI  - Use of azithromycin for the treatment of Campylobacter enteritis in travelers to
      Thailand, an area where ciprofloxacin resistance is prevalent.
AB  - We evaluated the use of azithromycin (500 mg) or ciprofloxacin (500 mg) daily for
      3 days for the treatment of acute diarrhea among United States military personnel
      in Thailand. Stool cultures were obtained and symptoms were recorded on study
      days 0, 1, 2, 3, and 10. Campylobacter species were the most common pathogen
      isolated (44 isolates from 42 patients). All Campylobacter isolates were
      susceptible to azithromycin; 22 were resistant to ciprofloxacin. Among the 42
      patients with campylobacter infection, there were 2 clinical and 6 bacteriologic
      treatment failures in the ciprofloxacin group and no treatment failures in the
      azithromycin group (P = .021 for bacteriologic failures). Overall, azithromycin
      was as effective as ciprofloxacin in decreasing the duration of illness (36.9
      hours vs. 38.2 hours, respectively) and the number of stools (6.4 vs. 7.8,
      respectively). Among those not infected with Campylobacter species (n = 30), the
      duration of illness was 32.9 hours vs. 20.7 hours (P = .03) for the azithromycin
      and ciprofloxacin groups, respectively. Azithromycin is superior to ciprofloxacin
      in decreasing the excretion of Campylobacter species and as effective as
      ciprofloxacin in shortening the duration of illness. Azithromycin therapy may be
      an effective alternative to ciprofloxacin therapy in areas where ciprofloxacin
      resistant Campylobacter species are prevalent.

PMID- 8527540
TI  - Antimicrobial-resistant Campylobacter species--a new threat to travelers to
      Thailand.

PMID- 8527541
TI  - Meropenem versus tobramycin plus clindamycin for treatment of intraabdominal
      infections: results of a prospective, randomized, double-blind clinical trial.
AB  - The efficacy of meropenem was compared to that of the combination of tobramycin
      plus clindamycin (T/C) in a multiinstitutional clinical trial of treatment for
      patients suffering intraabdominal infection. Among the 177 patients enrolled and
      randomized, 127 were clinically evaluable and 86 were microbiologically
      evaluable. Analysis of data on an intent-to-treat basis for all randomized
      patients and on the basis of a successful outcome (absence of any infection) for
      clinically evaluable patients failed to detect any difference in efficacy between
      the two treatments. Infection was cleared in 92% of meropenem- and 89% of T/C
      treated clinically evaluable patients. Eradication of pathogens also was similar
      in the two treatment groups. Overall, adverse drug experiences were comparable
      between the two treatment groups, with the exception of an increase in serum
      creatinine level (which occurred more frequently in patients receiving T/C).
      Meropenem appears to be efficacious for the treatment of intraabdominal
      infections.

PMID- 8527542
TI  - Congenital Chagas' disease: diagnostic and clinical aspects.
AB  - The diagnostic and clinical aspects of congenital Chagas' disease were studied in
      71 children in Buenos Aires. The children's ages ranged from 2 days to 10 years.
      In infants < 6 months old, the disease was diagnosed by detection of Trypanosoma
      cruzi in the blood; the microhematocrit test was positive in 38 (97.4%) of 39
      cases. This test was the fastest and most reliable diagnostic method in this
      group, whereas two conventional serological methods were useful in children > or
      = 6 months of age. Forty-six (64.8%) of the 71 children had no clinical signs of
      infection. The clinical sign most frequently documented was hepatomegaly (18.3%).
      Three children were coinfected with human immunodeficiency virus; the latter
      infection was severe in two instances. Nifurtimox (10-15 mg/[kg.d] for 2 months)
      was used for parasiticidal treatment, and use of this drug resulted in mild
      adverse effects.

PMID- 8527543
TI  - Transmission of zidovudine-resistant human immunodeficiency virus type 1 variants
      following deliberate injection of blood from a patient with AIDS: characteristics
      and natural history of the virus.
AB  - We describe the development and persistence of severe immunodeficiency in a
      previously healthy young woman shortly after she was deliberately injected with
      blood that was drawn from a patient with AIDS. The heterogenous populations of
      human immunodeficiency virus (HIV) in donor and recipient were as closely related
      as those reported in previous cases of proven transmission. The relatively large
      proportion of non-syncytium-inducing (NSI) clones in the recipient suggests a
      selective but not complete suppression of syncytium-inducing (SI) viruses. The
      continuous presence of SI viruses might explain the severe immunosuppression that
      persisted once the recipient seroconverted. A codon 215 mutation (indicative of
      zidovudine resistance) was present in SI and NSI clones of the donor and in NSI
      clones of the recipient. The relative increase in codon 215 resistance mutation
      in the absence of zidovudine therapy was secondary to the increase in NSI clones.
      Findings in this case suggest that qualities of an inoculum and/or the route of
      transmission are important determinants in the subsequent clinical course of HIV
      disease.

PMID- 8527544
TI  - Transmission of fluconazole-resistant Candida albicans between patients with AIDS
      and oropharyngeal candidiasis documented by pulsed-field gel electrophoresis.
AB  - Electrophoretic karyotype and restriction endonuclease analysis of genomic DNA
      were used for the typing of nine isolates of Candida albicans from the oral
      cavities of two patients with AIDS--a husband and wife--whose infections became
      resistant to treatment with fluconazole (400 mg/d). The in vitro susceptibilities
      of sequential isolates to fluconazole and two other triazoles, itraconazole and
      the investigational drug D0870, were also evaluated. DNA analysis showed that the
      isolates responsible for fluconazole-resistant episodes of oropharyngeal
      candidiasis in the two patients were genetically related. In vitro susceptibility
      to fluconazole correlated well with clinical outcome. Although the minimal
      inhibitory concentrations of itraconazole and D0870 for fluconazole-resistant
      isolates were higher than those for fluconazole-susceptible isolates, both of the
      former triazoles exhibited good in vitro activity against the isolates tested.

PMID- 8527545
TI  - Infectiousness of a university student with laryngeal and cavitary tuberculosis.
      Investigative team.
AB  - A search for the source of infection for four children with tuberculosis (TB)
      identified a university student with cavitary and laryngeal TB. An investigation
      was conducted at the university, including tuberculin skin test (TST) screening
      and the use of questionnaires, chest radiographs, and DNA fingerprint analyses of
      Mycobacterium tuberculosis isolates. Six students with active TB were identified.
      All were linked to the source case. TSTs were positive for 22.4% of 419 students
      who had contact with the source case vs. 3.6% of 1,306 students without contact.
      The odds of a positive TST increased to 9.0 with 80 hours of classroom contact.
      Infectiousness increased significantly in the last of three semesters during
      which the source case was symptomatic (RR of a positive TST in classmates, 4.8;
      95% CI, 1.8-11.8). TST conversions were documented in 23 students; eight had, at
      most, 5 hours of classroom contact. The source case was highly infectious;
      transmission following only a few hours of exposure was documented. Her
      infectiousness increased as her clinical course progressed. This report
      illustrates the potential infectiousness of TB cases and demonstrates important
      aspects of tuberculosis control.

PMID- 8527546
TI  - Human herpesvirus 6 is associated with focal encephalitis.
AB  - Human herpesvirus 6 (HHV-6) is a cause of roseola infantum. Recent reports
      associate HHV-6 with cases of encephalitis; however, conclusive etiologic data do
      not exist. We evaluated clinical data and laboratory specimens obtained from
      patients with focal encephalitis of unknown etiology. Cerebrospinal fluid (CSF)
      specimens were tested by polymerase chain reaction for the presence of HHV-6 DNA.
      Selected samples were analyzed by DNA sequencing. We detected HHV-6 DNA in the
      CSF of nine of 138 patients. DNA sequencing revealed that group B strains of HHV
      6 were present in those specimens that were analyzed. No significant differences
      could be demonstrated in clinical presentation, laboratory findings, or
      neurodiagnostic imaging results between the nine patients with confirmed HHV-6
      infection and the 129 patients without evidence of HHV-6 infection. Neurological
      outcome for the nine HHV-6-infected patients varied from complete recovery
      without neurological deficit to death. Further prospective study is warranted.

PMID- 8527547
TI  - Clinical features and outcome of severe malaria in Gambian children.
AB  - The clinical and laboratory features of severe falciparum malaria in 180 Gambian
      children were studied between 1985 and 1989. Of the 180 children, 118 (66%)
      presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed
      seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died.
      Respiratory distress was a common harbinger of a fatal outcome. The differences
      in admission parasite counts in the blood, hematocrit, and opening cerebrospinal
      pressures for patients who died and survivors were not significant. A multiple
      logistic regression model identified neurological status (coma, particularly if
      associated with extensor posturing), stage of parasite development on the
      peripheral blood film, pulse rate of > 150 or respiratory rate of > 50,
      hypoglycemia, and hyperlactatemia (plasma lactate level, > 5 mmol/L) as
      independent indicators of a fatal outcome. Biochemical evidence of hepatic and
      renal dysfunction was an additional marker of a poor prognosis, but, in contrast
      to severe malaria in adults, none of these children with severe malaria had acute
      renal failure.

PMID- 8527548
TI  - Control of nosocomial infections in an intensive care unit in Guatemala City.
AB  - We tested the effectiveness of specific vs. general infection control
      interventions in a teaching hospital in Guatemala City. After 3 months of
      prospective surveillance, we implemented targeted interventions (i.e.,
      modification of respiratory tract care and use of a closed urinary catheter
      drainage system), an educational program focused on respiratory intervention, and
      general interventions (i.e., aseptic technique). The rate of nosocomial
      pneumonia, the most common nosocomial infection, decreased from 33% (41 of 123
      patients) before intervention to 16% (21 of 130 patients) after intervention (P =
      .001). Although the frequency of hand washing increased from 5% to 63% (P <
      .001), the rates of other types of nosocomial infections did not change
      significantly. The combination of targeted respiratory intervention and an
      intense, focused educational campaign reduced the rate of nosocomial pneumonia.
      General improvements in hygiene and hand washing rates, or even implementation of
      a closed urinary drainage system without focused education, may not be sufficient
      to reduce infection rates in intensive care units in developing countries.

PMID- 8527549
TI  - Adverse events associated with high-dose rifabutin in macrolide-containing
      regimens for the treatment of Mycobacterium avium complex lung disease.
AB  - We initiated a multidrug trial that included high-dose rifabutin for the
      treatment of pulmonary Mycobacterium avium complex (MAC) disease. Twenty-six
      patients received rifabutin (600 mg/d) in combination with ethambutol,
      streptomycin, and either clarithromycin (500 mg b.i.d.; 15 patients) or
      azithromycin (600 mg/d; 11 patients). Rifabutin-related adverse events occurred
      in 77% of patients. Fifty-eight percent of patients required a dosage adjustment
      or discontinuance of rifabutin therapy. The most common adverse event was a
      reduction in the mean total white blood cell (WBC) count, which decreased from
      8,600 +/- 2,800/mm3 before treatment to 4,500 +/- 2,100/mm3 during treatment (P =
      .0001). Although all patients had some decrease in WBC count, only three patients
      (12%) required a dosage adjustment for this reason. Other common adverse events
      included gastrointestinal symptoms (nausea, vomiting, or diarrhea; 42%) and
      abnormal liver enzyme levels (12%). Eight of 11 patients (73%) with
      gastrointestinal symptoms, including one patient with abnormal liver enzyme
      levels, required a rifabutin-dosage adjustment. The most severe adverse events,
      always requiring an adjustment of therapy, were a diffuse polyarthralgia syndrome
      (19%) and anterior uveitis (8%). The latter toxicity has previously been reported
      to occur only in patients with AIDS and was seen only in patients who also were
      receiving clarithromycin. On the basis of the current findings, we recommend that
      rifabutin be used at a dose of 300 mg/d in multidrug regimens that include a
      macrolide for treatment of MAC lung disease.

PMID- 8527550
TI  - Efficacy of permethrin-impregnated uniforms in the prevention of malaria and
      leishmaniasis in Colombian soldiers.
AB  - We determined the efficacy of the use of permethrin-impregnated uniforms for
      prevention of malaria and leishmaniasis in a double-blind, randomized study of
      Colombian soldiers on patrol. In the study of malaria, soldiers were issued
      impregnated uniforms (i.e., a shirt, an undershirt, pants, socks, and a hat) or
      uniforms washed in water; the soldiers wore the uniforms day and night for a mean
      of 4.2 weeks and were observed for an additional 4 weeks. Three (3%) of 86
      soldiers wearing impregnated uniforms contracted malaria, whereas 12 (14%) of 86
      soldiers wearing control uniforms contracted malaria (P = .015). In the study of
      leishmaniasis (soldiers were in the area of endemicity for 6.6 weeks and were
      observed for 12 weeks thereafter), 4 (3%) of 143 soldiers wearing impregnated
      uniforms and 18 (12%) of 143 soldiers wearing control uniforms acquired disease
      (P = .002). In the leishmaniasis study, and presumably in the malaria study,
      breakthrough infections in the treated group were primarily due to bites in
      unclothed regions of the body (face and hands). Permethrin-treated uniforms were
      virtually nontoxic (there were only two cases of mild skin irritation among 229
      subjects), and impregnation is quick and inexpensive. Impregnation of clothing
      with permethrin is suggested for nonimmune populations who are likely to be
      exposed to malaria or leishmaniasis over a period of 1-2 months.

PMID- 8527551
TI  - Clinical presentation of minimally invasive and in situ squamous cell carcinoma
      of the anus in homosexual men.
AB  - From January 1988 to December 1993, we identified six men with minimally invasive
      (stage I) squamous cell carcinoma of the anus and 10 men with anal carcinoma in
      situ (CIS). Of the six patients with invasive carcinoma, four were infected with
      human immunodeficiency virus (HIV), including one with AIDS. Of the 10 patients
      with CIS, eight were infected with HIV, including four with AIDS. Anal pain and
      bleeding were the most common symptoms of minimally invasive anal cancer and anal
      CIS. Anal irritation, burning, or pruritus occurred more frequently in patients
      with CIS, whereas anal ulcers, masses, or abscesses were more frequent in
      patients with minimally invasive cancer. Several patients with CIS had a discrete
      area of leukoplakia in the anal canal or a pigmented plaque of the anus and anal
      canal. These lesions were not observed in patients with minimally invasive anal
      cancer. The symptoms and signs of early-stage anal cancer in men at risk for
      developing HIV infection or men infected with HIV often resemble those of other
      common anorectal diseases in homosexual men. Anal cancer in HIV-infected men is
      not limited to those individuals with AIDS.

PMID- 8527552
TI  - Humoral immune responses in acute schistosomiasis mansoni: relation to morbidity.
AB  - An analysis of 25 individuals simultaneously exposed to cercariae of Schistosoma
      mansoni showed that morbidity (measured by the clinical/sonographic index) was
      more severe in patients with high-level egg output, irrespective of age or
      intensity of water contact. High levels of IgM and IgG antibodies to keyhole
      limpet hemocyanin and of IgA antibody to soluble egg antigen were documented
      predominantly during the acute phase of illness. Increased levels of these
      antibodies and of IgM antibody to soluble egg antigen correlated positively with
      morbidity after adjustment for age and intensity of water contact.

PMID- 8527553
TI  - Quantity and avidity of pneumococcal antibodies before and up to five years after
      pneumococcal vaccination of elderly persons.
AB  - It is not known how long vaccine-induced type-specific pneumococcal antibodies
      persist or whether age-related changes in their avidity occur; we therefore
      administered pneumococcal vaccine to 15 elderly persons aged 60-67 years to
      determine the level and avidity of the pneumococcal antibodies before vaccination
      and again 4 weeks and 5 years later. Antibody levels were significantly higher
      after vaccination than before vaccination in 67% of these subjects (P < .01). On
      the basis of guidelines established for revaccination, we found that 60% of these
      elderly persons required revaccination 5 years after primary immunization and
      that the antibody status of the remaining 40% would need to be determined some
      years later. No significant differences in IgG antibody avidity were detected in
      connection with the type of pneumococcus, the vaccination status of the vaccinee
      (i.e., whether sera were assayed before vaccination or 4 weeks or 5 years later),
      or the age of the vaccinee.

PMID- 8527554
TI  - Acute viral hepatitis in Saudi Arabia: seroepidemiological analysis, risk
      factors, clinical manifestations, and evidence for a sixth hepatitis agent.
AB  - We conducted a prospective, descriptive cohort study of all 217 cases of acute
      viral hepatitis (AVH) seen in adults during 1992 at the sole hospitals with
      infectious disease departments in the second and third largest cities in the
      Kingdom of Saudi Arabia. In addition, we undertook a nested case-control study.
      Our goals were (1) to determine the causes, demographics, risk factors, and
      clinical characteristics of AVH in the Kingdom; (2) to evaluate the reliability
      of diagnostic tests for acute hepatitis C and E; and (3) to assess the relative
      importance, characteristics, and risk factors of a sixth hepatitis agent, non-A
      E. All cases and controls completed a questionnaire. Cases provided blood samples
      for studies of serum bilirubin, alanine and aspartate aminotransferases, and
      antibody to hepatitis viruses as well as genome detection studies. The results of
      serological and molecular tests were used to categorize each case as hepatitis A,
      B, C, D, E, or non-A-E. Historical, clinical, and laboratory determinants were
      statistically analyzed by comparisons between groups with different types of AVH
      and controls. Analysis of risk factors suggested that hepatitis C and D were
      parenterally transmitted, while hepatitis A, E, and non-A-E were not; the route
      of transmission of hepatitis B was unclear. Hepatitis E was strongly associated
      with living or traveling on the Indian subcontinent. The clinical disease caused
      by all six agents was indistinguishable. The putative sixth agent caused 13% of
      cases. The second-generation tests for antibody to HCV and HEV were relatively
      reliable for the diagnosis of AVH.

PMID- 8527555
TI  - Pulmonary cryptococcosis: localized and disseminated infections in 27 patients
      with AIDS.
AB  - We reviewed the records of 85 patients infected with both human immunodeficiency
      virus and Cryptococcus neoformans. Twenty-seven patients (32%) had pulmonary
      cryptococcosis. C. neoformans was cultured from bronchoalveolar lavage (BAL) or
      pleural fluid in 25 cases; the remaining two patients had cryptococcal antigen
      (CA) detected in BAL fluid and C. neoformans cultured from other sites. All but
      one of the 27 patients had detectable CA in serum. The CD4+ lymphocyte count was
      low in all cases (median, 24/mm3). Clinical manifestations of pulmonary
      cryptococcosis included fever (94%), cough (71%), dyspnea (7%), expectoration
      (4%), chest pain (2%), and hemoptysis (1%). Diffuse interstitial opacities
      (70.5%), focal interstitial abnormalities, alveolar opacities, adenopathies,
      cavitary lesions, and pleural effusions were evident. Outcome was poor (mean
      survival time, 23 weeks) despite treatment. Patients with localized pulmonary
      cryptococcosis appeared to have a higher CD4+ lymphocyte count, an earlier
      diagnosis, lower serum CA titers, fewer previous or concomitant infections, and a
      better prognosis than patients with disseminated cryptococcosis.

PMID- 8527556
TI  - Emergence of multidrug resistance in Campylobacter jejuni isolates from three
      patients infected with human immunodeficiency virus.
AB  - Single-drug resistance to tetracycline, doxycycline, erythromycin, or
      fluoroquinolones in Campylobacter isolates recovered from humans has been
      documented worldwide. Multidrug resistance to these antibiotics is rare in
      Campylobacter jejuni. We report the sequential development of multidrug
      resistance in C. jejuni isolates from three patients who were infected with human
      immunodeficiency virus. Multiple isolates recovered from stool specimens from
      these patients were ribotyped, and antibiotic susceptibility profiles were
      determined. The results indicated that each patient was infected with a single
      strain of C. jejuni that had progressively acquired resistance to the antibiotics
      used during treatment. The emergence of resistant isolates appeared to correlate
      with clinical relapse. In these patients, campylobacter enteritis was prolonged,
      severe, and relapsing, and antimicrobial therapy was required. Once these first
      line antibiotics become ineffective, few other antibiotics are available for
      treating patients with campylobacter enteritis. Acquisition of antibiotic
      resistance in C. jejuni is therefore of concern in these cases.

PMID- 8527557
TI  - Frequency of unrecognized Bordetella pertussis infections in adults.
AB  - To investigate the frequency of unrecognized Bordetella pertussis infections in
      adults, we performed IgA and IgG ELISA antibody studies with four B. pertussis
      antigens--i.e., lymphocytosis-promoting factor, filamentous hemagglutinin,
      pertactin, and fimbriae-2--in 51 health care workers from whom six consecutive
      yearly serum samples (from 1984 to 1989) were available. Overall, 90% of the
      subjects had a significant increase in antibody (IgA or IgG) to one or more
      antigens between 2 consecutive years during the 5-year study period; 55% of
      subjects had evidence of two infections, 17% had three infections, and 4% had
      four infections. Infections occurred in all study years, with the following
      rates: 1984-1985, 32%; 1985-1986, 24%; 1986-1987, 40%; 1987-1988, 29%; and 1988
      1989, 43% (P = .12). Some antibody rises may have been due to responses to cross
      reacting antigens (Bordetella parapertussis, nontypable Haemophilus influenzae),
      but overall these data suggest that B. pertussis infections in adults are common,
      endemic, and usually unrecognized.

PMID- 8527558
TI  - Clinical features that differentiate hantavirus pulmonary syndrome from three
      other acute respiratory illnesses.
AB  - To elucidate the early clinical characteristics of hantavirus pulmonary syndrome
      (HPS), we compared the clinical features of 24 cases of HPS with those of cases
      of bacteremic pneumococcal pneumonia (n = 30), influenza (n = 33), or unexplained
      adult respiratory distress syndrome (ARDS, n = 21). On admission, patients with
      HPS were less likely than outpatients with influenza to have reported sore throat
      (OR = 0.02, P < .01) and cough (OR = 0.1, P = .01) and were less likely than
      patients with pneumococcal pneumonia to have lobar infiltrates detected by chest
      roentgenography (OR = 0, P < .01). Multivariate discriminant analysis revealed
      that three clinical characteristics at admission (dizziness, nausea or vomiting,
      and absence of cough) and three initial laboratory abnormalities (low platelet
      count, low serum bicarbonate level, and elevated hematocrit level) served to
      identify all patients with HPS and to exclude HPS in at least 80% of patients
      with unexplained ARDS. These findings warrant further study and should facilitate
      the early recognition of patients with HPS, who may benefit from early critical
      care intervention.

PMID- 8527559
TI  - An outbreak of plague in northwestern province, Zambia.
AB  - Three cases of plague, all with pneumonic involvement, occurred in a small
      village in northwestern Zambia. Initial recognition of the diagnosis was delayed,
      but the outbreak was terminated by rapid intervention with insecticides and with
      the use of chemoprophylaxis for individuals with high-risk exposures to case
      patients.

PMID- 8527560
TI  - Tuberculosis caused by Mycobacterium africanum associated with involvement of the
      upper and lower respiratory tract, skin, and mucosa.
AB  - Cutaneous tuberculosis is rarely seen in industrialized countries and is usually
      caused by Mycobacterium tuberculosis. We report a case of cutaneous tuberculosis
      with bilateral nodular scleritis, nasal sinus invasion, and nasal septum
      perforation (confirmed by computed tomography scans of the sinuses), associated
      with pulmonary infiltrates and mediastinal adenopathy, in an African woman.
      Mycobacterium africanum was recovered from the sputum after 8 weeks of culture in
      Lowenstein-Jensen medium. To our knowledge, this is the first description of M.
      africanum associated with cutaneous tuberculosis and nasal sinus invasion.

PMID- 8527561
TI  - Adverse cutaneous reactions to pyrimethamine/sulfadiazine and
      pyrimethamine/clindamycin in patients with AIDS and toxoplasmic encephalitis.
AB  - We assessed the value of clinical and laboratory parameters for predicting the
      occurrence of skin reactions induced by pyrimethamine/sulfadiazine and
      pyrimethamine/clindamycin and the effects of continued therapy for patients with
      these reactions. We retrospectively studied all episodes of toxoplasmic
      encephalitis in patients with AIDS who were treated with
      pyrimethamine/sulfadiazine or pyrimethamine/clindamycin. Eighteen (75%) of 24
      patients treated with pyrimethamine/sulfadiazine had cutaneous reactions after a
      mean of 11 days, whereas 15 (58%) of 26 patients treated with
      pyrimethamine/clindamycin had cutaneous reactions after a mean of 13 days (P =
      .56). Nine (50%) of the 18 patients continued to be treated with
      pyrimethamine/sulfadiazine throughout the duration of hypersensitivity, compared
      with all 15 patients who were treated with pyrimethamine/clindamycin (P = .002).
      Nine patients had to stop therapy with pyrimethamine/sulfadiazine (two had
      Stevens-Johnson syndrome and one had Lyell's syndrome). Thus, treatment
      throughout the duration of hypersensitivity is more likely to succeed for
      patients receiving pyrimethamine/clindamycin, whereas therapy with
      pyrimethamine/sulfadiazine is associated with a high risk of Lyell's syndrome and
      Stevens-Johnson syndrome.

PMID- 8527562
TI  - Value of skin testing for predicting reactions to equine rabies immune globulin.
AB  - The high cost of postexposure prophylaxis for rabies is one reason that treatment
      is inadequate in developing countries. This problem has kindled interest in the
      use of equine rabies immune globulin, which is a less expensive, yet effective,
      substitute for human rabies immune globulin. Fatal anaphylaxis is a feared
      complication of the administration of heterologous serum; therefore,
      authoritative sources recommend prior skin testing. However, recommendations for
      methods of administering such a skin test and for its interpretation vary
      greatly. We embarked on a long-term study to develop guidelines for
      administration and interpretation of skin test results and to eventually
      determine a cost-benefit ratio. The skin test is not predictive of serum
      sickness. Anaphylaxis is rare with modern purified and pepsin-digested equine
      rabies immune globulins. We consider a skin test to be positive only if a wheal
      of > 10 mm in diameter, with or without flare, or a wheal of 5-10 mm in diameter
      with a flare of > 20 mm develops. Long-term studies will be required to answer
      the remaining questions regarding test criteria and cost benefits.

PMID- 8527563
TI  - Atypical leishmaniasis in a patient infected with human immunodeficiency virus.
AB  - Visceral leishmaniasis is an anthropozoonosis endemic in the south of France. Its
      occurrence among patients infected with human immunodeficiency virus (HIV), in
      whom it presents with uncommon clinical, biological, and evolutionary signs, is
      being reported more and more often. We describe a case of leishmaniasis in an HIV
      seropositive man that we believe is unique with respect to the cutaneous and then
      visceral location of the disease and the discovery at necropsy of an adrenal and
      myocardial leishmanial infiltrate.

PMID- 8527564
TI  - Rethinking CD4+ T cell counts for individuals who recently seroconverted to human
      immunodeficiency virus.
AB  - The distribution of initial CD4+ T lymphocyte counts for individuals who have
      recently seroconverted to human immunodeficiency virus (HIV) is broad. We review
      major articles describing CD4 cell counts shortly after documented HIV infection
      and discuss both the possible sources of variability in these studies and the
      clinical importance of recognizing that even recently infected patients may have
      low CD4 cell counts and thus will require therapeutic intervention with
      antiretroviral agents or prophylactic antibiotics.

PMID- 8527565
TI  - Aseptic meningitis caused by sandfly fever virus, serotype Toscana.
AB  - Sandfly fever virus, serotype Toscana (TOS), is endemic in some Mediterranean
      countries and causes sandfly fever (pappataci fever). In some patients, TOS may
      cause meningitis and meningoencephalitis. We report on two German adults
      returning from Italy with TOS-related meningitis, complicated in one case by
      abducens nerve palsy. TOS infection should be considered as a cause of acute
      central nervous system disorders in patients returning from areas of endemicity.

PMID- 8527566
TI  - Deep tissue infections caused by Scopulariopsis brevicaulis: report of a case of
      prosthetic valve endocarditis and review.
AB  - Scopulariopsis brevicaulis is a saprophytic fungus that commonly causes
      onychomycosis but rarely causes deep tissue infection. To the best of our
      knowledge, this is the first reported case of endocarditis caused by S.
      brevicaulis. The infection persisted despite two aortic valve replacements,
      debridement, and prolonged therapy with several antifungal agents. The patient
      eventually died due to an acute myocardial infarction caused by ongoing
      prosthetic valve endocarditis. We review case reports of deep tissue infections
      due to Scopulariopsis species.

PMID- 8527567
TI  - Strongyloidiasis in patients with hematologic malignancies.
AB  - We retrospectively studied 343 consecutive patients treated between 1979 and
      1992. Ninety patients whose stool was not examined were excluded. Fifty-three
      patients with strongyloidiasis were compared with 200 controls with regard to
      outcomes and the following characteristics: age, sex, underlying disease, use of
      corticosteroids, abdominal pain, diarrhea, fever, pulmonary symptoms, and
      eosinophilia. Patients with strongyloidiasis more commonly had eosinophilia (P =
      .01) and fever (P = .03). There was a single but fatal case of the disseminated
      disease syndrome (1.9% of patients with strongyloidiasis). In multiple logistic
      regression analysis, the factors predictive for strongyloidiasis were
      schistosomiasis (odds ratio [OR], 6.58), ascariasis (OR, 2.78), and the use of
      steroids (OR, 2.29). Strongyloidiasis was highly prevalent among patients with
      hematologic malignancies in Brazil. Occurrence of the disseminated disease
      syndrome seems to be unusual.

PMID- 8527568
TI  - Veillonella myositis in an immunocompromised patient.
AB  - Infectious myositis is rather uncommon. When caused by anaerobic organisms,
      myositis is usually polymicrobial. Trauma, ischemia, or a contiguous focus of
      infection is often an antecedent of myositis. We report a case of monomicrobial
      veillonella myositis in an immunocompromised patient. The infection responded to
      debridement and therapy with metronidazole.

PMID- 8527569
TI  - Prolonged isolated fever due to attenuated extracerebral toxoplasmosis in
      patients infected with human immunodeficiency virus who are receiving
      trimethoprim-sulfamethoxazole as prophylaxis.
AB  - We report two cases of prolonged fever in deeply immunocompromised patients with
      AIDS who had been receiving trimethoprim-sulfamethoxazole (TMP-SMZ) as primary
      prophylaxis for several months. Investigations of the cause of fever yielded
      normal or negative findings except that the polymerase chain reaction (PCR) for
      Toxoplasma gondii in the blood was positive in both cases, and PCR of the
      bronchoalveolar lavage fluid was positive in one case. After a few days of
      treatment with pyrimethamine plus clindamycin, the two patients became afebrile
      and the T. gondii PCR became negative. The patients probably had disseminated
      toxoplasmosis attenuated by TMP-SMZ. PCR examination of blood for evidence of T.
      gondii genome may be useful in screening for causes of unexplained fever in
      patients with AIDS, even those who receive prophylaxis with TMP-SMZ.

PMID- 8527570
TI  - Fatal genitourinary mucormycosis in a patient with undiagnosed diabetes.
AB  - We present what we believe is the first report in the world literature of penile
      necrosis due to mucormycosis, a rare and often fatal fungal infection. This case
      of rhizopus mucormycosis began with a penile lesion in a 27-year-old patient with
      undiagnosed diabetes; it led to necrosis of the phallus, lower urinary tract,
      rectum, and pelvic musculature and finally to death. Despite repeated aggressive
      surgical debridement in conjunction with medical therapy, we were unable to halt
      the progression of the fungal and synergistic bacterial infections.

PMID- 8527571
TI  - Epidemiology of the colonization of inpatients and outpatients with ciprofloxacin
      resistant coagulase-negative staphylococci.
AB  - We tested the skin staphylococcal flora of inpatients and hospital staff in the
      orthopedic unit of Turku University Central Hospital (Turku, Finland) for
      susceptibility to ciprofloxacin. Ciprofloxacin-resistant coagulase-negative
      staphylococci were detected on the skin of 14 (61%) of the 23 inpatients and 16
      (53%) of the 30 members of the hospital staff. Plasmid profiles were highly
      similar for most of these resistant isolates, thus suggesting that cross
      infection was responsible for the spread of ciprofloxacin-resistant strains in
      the orthopedic unit. Colonization of inpatients with ciprofloxacin-resistant
      coagulase-negative staphylococci was significantly associated with
      hospitalization longer than 6 days (P = .006) and the use of antibiotics during
      the hospital stay (P = .009). Twelve of 30 outpatients with venous leg ulcers
      were treated with ciprofloxacin, and all of these 12 were colonized with
      ciprofloxacin-resistant coagulase-negative staphylococci; in contrast, only three
      (33%) of the nine outpatients who were treated with trimethoprim (P = .004) and
      three (33%) of the nine outpatients who were treated with placebo (P = .004) were
      colonized with these strains. The ciprofloxacin-resistant strains from the
      outpatients had distinctly different plasmid profiles, a finding that suggests
      that, in the community, ciprofloxacin resistance may have emerged in isolates
      from each treated individual.

PMID- 8527572
TI  - Cholera in a patient infected with human immunodeficiency virus.

PMID- 8527573
TI  - Pneumonia and respiratory distress syndrome during primary infection with
      Toxoplasma gondii.

PMID- 8527574
TI  - Plesiomonas shigelloides septicemia in a patient with primary hemochromatosis.

PMID- 8527575
TI  - Polymicrobial feculent meningitis.

PMID- 8527576
TI  - Propionibacterium acnes vertebral osteomyelitis following lumbar puncture: case
      report and review.

PMID- 8527577
TI  - Cellulitis and spondylitis due to Streptococcus pneumoniae.

PMID- 8527578
TI  - Pneumococcal soft-tissue infections.

PMID- 8527579
TI  - Postpartum retroperitoneal abscess due to Mycoplasma hominis.

PMID- 8527580
TI  - Elevated cytokine levels in a patient with AIDS and hypercalcemia: effects of
      therapy with pamidronate.

PMID- 8527581
TI  - Chronic diarrhea and bacteremia caused by Campylobacter lari in a neonate.

PMID- 8527582
TI  - Visceral leishmaniasis due to a Leishmania variant that shares kinetoplast DNA
      sequences with Leishmania braziliensis and Leishmania mexicana in a patient
      infected with human immunodeficiency virus: identification of the Leishmania
      species with use of the polymerase chain reaction.

PMID- 8527583
TI  - Reversible CD4+ T lymphocyte depletion in a patient who had disseminated
      histoplasmosis and who was not infected with human immunodeficiency virus.

PMID- 8527584
TI  - Update on the status of Lyme borreliosis in British Columbia, Canada.

PMID- 8527585
TI  - Bacteremic group A streptococcal pharyngitis presenting as acute airway
      obstruction.

PMID- 8527586
TI  - A predisposition toward Edwardsiella tarda bacteremia in individuals with
      preexisting liver disease.

PMID- 8527587
TI  - Meningitis caused by mixed anaerobic species complicating tethered cord syndrome.

PMID- 8527588
TI  - Use of cefotaxime and metronidazole for treating cerebral abscesses.

PMID- 8527589
TI  - Viral antibodies in chronic fatigue syndrome.

PMID- 8527590
TI  - Pancreatic necrosis following treatment of leishmaniasis with sodium
      stibogluconate.

PMID- 8527591
TI  - Efficacy of intermittent liposomal amphotericin B in the treatment of visceral
      leishmaniasis in patients infected with human immunodeficiency virus.

PMID- 8527592
TI  - Legionnaires' disease in patients infected with human immunodeficiency virus.

PMID- 8527593
TI  - Escherichia coli meningitis and septicemia associated with an epidural catheter.

PMID- 8527594
TI  - Brucellar bacteremia in pregnancy.

PMID- 8527595
TI  - Intrathecal synthesis of antibodies to human herpesvirus 6 early antigen in
      patients with meningitis/encephalitis.

PMID- 8527596
TI  - Histological evaluation of a biodegradable Polyactive/hydroxyapatite membrane.
AB  - Guided tissue regeneration (GTR) is a technique which is used for the treatment
      of bone defects associated with periodontal disease or enossal dental implants.
      In most experimental studies on GTR, non-degradable membranes are used. A
      drawback inherent to such devices is that at the end or in the course of the
      wound healing they have to be removed. Therefore, the aim of the present study
      was to investigate a new biodegradable membrane material for use in GTR, which
      also has excellent mechanical properties and is biocompatible. The material is a
      composite consisting of poly(ethyleneglycol terephthalate) and poly(butylene
      terephthalate) segmented copolymer (PEG/PBT), which for the experiments was used
      in pure form and also mixed with hydroxyapatite (HA) grains. Subcutaneous and
      subgingival implantation studies in goats were performed to determine the
      biocompatibility and biodegradability characteristics of several of these
      materials. Differences between materials were introduced in the production
      process, PEG/PBT ratio, material thickness and presence of HA. Implantation
      periods were 3, 6 and 12 wk. The histological results indicated that all
      investigated materials were biocompatible with the surrounding tissue.
      Degradation of the membranes was attended by a mild cellular reaction. The
      degradation process was mainly influenced by the PEG/PBT ratio. A higher PBT
      content resulted in a decreased degradation.

PMID- 8527597
TI  - Amorphorization and recrystallization during plasma spraying of hydroxyapatite.
AB  - X-ray diffraction was used to characterize the dependence of mean crystallite
      size and crystallinity on the thickness of coatings. A fall in mean crystallite
      size but a rise in crystallinity with increased thickness was observed. The
      reason might be due to the differences in cooling rate of partially molten
      particles of hydroxyapatite. The thicker the coating, the longer the cooling
      time. The longer cooling time was beneficial to the occurrence of
      recrystallization. It was found that the critical thickness of recrystallization
      (rc) was about 20 microns.

PMID- 8527598
TI  - Degradation of high molecular weight poly(L-lactide) in alkaline medium.
AB  - To study the effect of molecular weight and morphology on hydrolytic degradation,
      four poly(L-lactide)s (PLLAs) with average molecular weight of 3.0 x 10(5), 4.5 x
      10(5), 6.5 x 10(5) and 3 x 10(6) were used. PLLA films with different
      morphologies were obtained by solution casting. Degradation of the films was
      performed at 37 degrees C in 0.01 N NaOH solution and this alkaline hydrolysis
      seemed to simulate well the real case while offering significant acceleration of
      the degradation process. Diverse microscopy techniques (light, polarizing and
      scanning electron) were used to study the surface change of morphology and
      erosion of the PLLA films. Swelling was visualized by scanning electron
      microscopy, particularly on the spherulites, which were eroded from the centre by
      hydrolysis. In the case of highly amorphous film, crystallization took place as
      degradation proceeded. The reduction in transparency of PLLA films, measured by a
      spectrophotometer at 570 nm, was ascribed to the increased density of
      spherulites. Differential scanning calorimetry revealed that the crystallinity of
      PLLA increased with degradation time, in accordance with accelerated spherulite
      formation.

PMID- 8527599
TI  - Blood perfusion and remodelling activity in canine tibial diaphysis after filling
      with a new bone cement compared to bone wax and poly(methyl methacrylate) cement.
AB  - Six dogs each had one tibia filled with standard poly(methyl methacrylate) (PMMA)
      bone cement and the contralateral tibia filled with a new methyl methacrylate-n
      decyl methacrylate-isobornyl methacrylate (MMA-DMA-IBMA) bone cement (Boneloc)
      with lowered polymerization heat and monomer leakage. An additional six dogs each
      had one tibia filled with MMA-DMA-IBMA and the contralateral tibia filled with
      bone wax. There was a higher diaphyseal blood flow, measured with a microsphere
      technique, in the legs filled with MMA-DMA-IBMA than in those filled with PMMA.
      The wax-filled bones presented higher blood perfusion than those with MMA-DMA
      IBMA. We found a tendency towards higher 99mtechnetium-labelled methylene
      diphosphonate (99mTcMDP) uptake, and autoradiograms revealed a tendency towards
      larger subperiosteal apposition and more blackening, both at the subperiosteal
      apposition and the cortex, in the bones filled with new bone cement in the first
      series, but in wax-filled bone in the second series. It is concluded that the new
      bone cement, compared to standard acrylic bone cement, seems to inhibit the
      vascular response and bone remodelling activity less, making earlier remodelling
      possible. However, the new bone cement still seems to inhibit bone blood
      perfusion compared to bone wax.

PMID- 8527600
TI  - Surface modifications of a glass and a glass-ceramic of the MgO-3CaO.P2O5-SiO2
      system in a simulated body fluid.
AB  - A glass of nominal composition (wt%) 17.25 MgO-52.75 3CaO.P2O5-30 SiO2 and a
      glass-ceramic obtained from it showed surface modifications when immersed in an
      acellular medium having a composition similar to that of human blood plasma. A
      (Ca, P)-rich layer, with an approximate Ca/P atomic ratio of 1.7, identified as
      hydroxyapatite, developed on both samples. The precipitated film on the glassy
      sample was weakly bonded, whereas that formed on the glass-ceramic was strongly
      adherent. The apatite precipitated during the in vitro tests on both samples grew
      as a needle-like structure with crystals about 150-200 nm long and 50-70 nm
      thick, as measured on specimens soaked for 1 month in the simulated body fluid
      (SBF). The presence of calcium and phosphate ions in the SBF contributed to the
      precipitation of the (Ca, P)-rich layers on both specimens.

PMID- 8527601
TI  - In vivo setting behaviour of fast-setting calcium phosphate cement.
AB  - The in vivo setting behaviour of fast-setting calcium phosphate cement (FSCPC)
      between femoral muscles of the rat was investigated to evaluate the possible
      value of FSCPC for medical and dental application. Conventional CPC (c-CPC) and
      FSCPC were implanted between femoral muscles, and various aspects of the setting
      behaviour such as setting time, mechanical strength and conversion ratio of
      cement into hydroxyapatite (HAP: Ca10(PO4)6(OH)2) were measured by the Vicat
      needle method, diametral tensile strength (DTS) measurement, and quantitative
      powder X-ray diffraction (XRD) analysis, respectively. The setting time of FSCPC
      in vivo was 5-7 min, in contrast to 48 min for c-CPC. As a result of its fast
      setting, set specimens of FSCPC showed higher mechanical strength from the
      initial stage than c-CPC. Higher DTS values were observed in FSCPC than c-CPC
      implanted after 24 h. Powder XRD analysis revealed faster conversion of FSCPC
      than c-CPC into HAP, which was responsible both for the faster setting and higher
      mechanical strength from the initial stage. We concluded, therefore, that FSCPC
      may be used for a wide range of clinical applications, i.e. fields where fast
      setting is required such as orthopaedic, plastic and reconstructive, and oral and
      maxillofacial surgery.

PMID- 8527602
TI  - Electron and mechanical properties of bone during heating, evaluated by
      exoelectron emission and ultrasound.
AB  - Exoelectron spectroscopy and ultrasound velocity (USV) measurements have been
      applied to analyse both the electron and mechanical behaviour of compact bone
      tissue and its main components--collagen and hydroxyapatite (HAP)--in the
      temperature range 20-80 degrees C. The special exoelectron method with additional
      IR illumination has been pioneered for the above objective. Thermally induced
      variations of the electron structure of bone tissue and HAP were manifested at 55
      degrees C, but in collagen they were near 75 degrees C. The greatest decrease in
      USV was at 35-65 degrees C in collagen and at 55-70 degrees C in bone. No changes
      of USV in HAP were revealed. The coincidence of temperatures of the exoemission
      maxima and of the USV most expressed gradient in fresh bone and collagen proves
      the correlation between electron and mechanical behaviour during heating,
      connected with the partial denaturation of collagen.

PMID- 8527603
TI  - Collagen and its interaction with chitosan. II. Influence of the physicochemical
      characteristics of collagen.
AB  - This work is a continuation of the study of the interactions which can occur when
      chitosan is in contact with bovine anticollagen. The major result of the first
      part was that under classical conditions, there exists a competition between
      collagen gelation and the formation of a pure polyanion-polycation complex with
      chitosan. In the present study, we have attempted to reach the 1:1 stoichiometry
      by two different methods. When collagen is denatured, the polyanion-polycation
      complex is improved, but the theoretical stoichiometry is not achieved. The
      presence of a large excess of chitosan gives rise to a second mechanism of
      interaction. Contrary to the case of the polyanion-polycation interaction, the
      latter seems to induce the denaturation of collagen. This behaviour is confirmed
      by infrared and circular dichroism spectrometries, as well as differential
      scanning calorimetry.

PMID- 8527604
TI  - Synthesis of phospholipid polymers having a urethane bond in the side chain as
      coating material on segmented polyurethane and their platelet adhesion-resistant
      properties.
AB  - Surface modification of segmented polyurethanes (SPUs) was carried out using new
      blood compatible polymers having both phospholipid polar groups and urethane
      bonds in the side chains. The polymers were composed of 2-methacryloyloxyethyl
      phosphorylcholine (MPC), n-butyl methacrylate (BMA) and methacrylate with a
      urethane bond (MU). The MPC copolymers were soluble in ethanol. The SPU membranes
      were immersed in an ethanol solution of MPC copolymers and dried in vacuo for
      coating. The surface formed was completely covered with the MPC copolymer which
      was confirmed by X-ray photoelectron spectroscopic analysis. The polymer coatings
      were hardly detached in water, ethanol and 40% aqueous solution of ethanol
      compared with poly(MPC-co-BMA) which did not have the MU moieties. Therefore, the
      MU moieties had affinity for the SPU. The surface modification of the SPUs
      suppressed platelet adhesion effectively after contact with platelet-rich plasma
      for 180 min.

PMID- 8527605
TI  - New artificial connective matrix made of fibrin monomers, elastin peptides and
      type I + III collagens: structural study, biocompatibility and use as tympanic
      membranes in rabbit.
AB  - Experiments leading to the conception and development of a new artificial
      connective matrix based on collagen-elastin-fibrin associations are presented.
      Preliminary evaluation of this biomaterial as an artificial tympanic membrane is
      described. Morphological evaluation was performed by histopathological and
      scanning electron microscopic studies. Biocompatibility was documented by
      subcutaneous implantation and experimental grafting in rabbits was performed with
      histopathological studies of the tympanic grafted membranes. The positive results
      obtained in this experimental study enable future studies in humans to be
      prepared.

PMID- 8527606
TI  - A pivotal role for TGF-beta in atherogenesis?

PMID- 8527607
TI  - Regeneration in the vertebrate central nervous system: phylogeny, ontogeny, and
      mechanisms.

PMID- 8527608
TI  - Population cycles in northern small mammals.
AB  - I. The regular multiannual oscillations of small mammals at northern latitudes
      have been a subject of intensive study from the beginning of this century. The
      existence of a subjective bias in the research due to different schools of study
      together with a long series of failures and seemingly contradictory results in
      experiments testing a multitude of hypotheses have brought confusion to the field
      of study. Much of this confusion has resulted from a failure to recognize sharply
      the problem studied, which in turn has masked the progress made during the years.
      Northern mammal cycles are not a single problem but a composition of many related
      problems. Every problem may have a single-factor explanation, but even with a
      single-factor explanation, one factor is not necessarily an answer to all of the
      related problems. 2. At present, we can state that the cyclicity is caused by a
      predator-prey interaction. Both the 8-11-year and the 3-5-year cycles may be
      special cases of a more general cycle, most likely caused by a herbivore-resident
      specialist predator interaction, where the period of the cycles is determined by
      size-related constraints affecting the increase rate of the populations. The
      factors determining the amplitude of the cycles probably vary regionally and/or
      temporally. The operation of generalist and nomadic predators is largely
      responsible for the regional and geographic synchrony in cycles, although
      climatic factors may also contribute to the geographic synchrony. The northern
      distribution of animal communities; both these factors affect the density of
      generalist predators, which act as a stabilizing factor in the system. The age
      related survival pattern seems to be mainly caused by predation, and the
      cyclically fluctuating reproductive output and mean body mass may be caused by
      changes in prey behaviour in response to fluctuating predation risk. Thus, we can
      already give a plausible explanation for most problems related to northern mammal
      cycles. 3. In all problems discussed, predation seems to be involved, and in most
      problems, it seems to be the factor which explains the observed patterns. Thus,
      as a generalization, it can be said that predation seems to be the key factor in
      the explanation of the northern multiannual cycles of small mammals. 4. There
      seems to be a linkage between diversity and cyclicity, probably because the
      diversity of the community (the number of prey species available) may determine
      the diet choice of a predator, which in turn determines whether the predators
      have a stabilizing or a destabilizing impact on prey populations.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8527609
TI  - Review article: the development of atrophic gastritis--Helicobacter pylori and
      the effects of acid suppressive therapy.
AB  - Helicobacter pylori is uniquely adapted to survival in the strongly acidic
      gastric lumen. In vitro, both acid and certain acid suppressors affect bacterial
      growth. In vivo, there is little evidence that acid suppressors have any effect
      on bacterial survival. In contrast, decrease of acid secretion quickly leads to a
      spreading of the bacterial infection throughout the body and fundus of the
      stomach, which is accompanied by an increase of the associated gastritis.
      Helicobacter pylori gastritis may, in a substantial number of infected subjects,
      ultimately lead to atrophy and intestinal metaplasia, conditions with an
      increased risk for gastric cancer. This review summarizes the data on the
      interrelation between Helicobacter pylori, gastric acid secretion and development
      of atrophic gastritis.

PMID- 8527610
TI  - Review article: gastrin releasing peptide and its value in assessing gastric
      secretory function.
AB  - Gastrin releasing peptide (GRP) has proved to be a particularly valuable tool in
      detecting disturbances of gastric secretory function associated with duodenal
      ulcer disease and Helicobacter pylori infection, and it has furthered
      understanding of the pathophysiology of these conditions. Its attractiveness lies
      in the fact that it simultaneously activates many physiological control
      processes, both stimulatory and inhibitory. This facilitates the detection of a
      defect in any of the many controls involved in regulating biological function.
      Other gastrointestinal functions such as gall-bladder contraction, pancreatic
      secretion and gastrooesophageal motility are also subject to complex regulatory
      controls, and GRP may also be of value in investigating disturbances of these
      processes.

PMID- 8527611
TI  - Review article: the relative effectiveness of somatostatin and octreotide therapy
      in pancreatic disease.
AB  - Somatostatin and octreotide inhibit basal and stimulated pancreatic secretion,
      stimulate reticuloendothelial system activity, modulate the cytokine cascade and
      are cytoprotective with respect to the pancreas. These effects of somatostatin
      and octreotide suggest that both drugs may be useful either in the treatment of
      pancreatic disorders, or in preventing acute pancreatitis following procedures on
      the pancreas. In recent years it has become clear that somatostatin is a useful
      and effective therapy for severe acute pancreatitis and in preventing
      complications following endoscopic retrograde cholangiopancreatography (ERCP),
      whereas octreotide has no beneficial effect and may be deleterious in both these
      indications. The differences in the therapeutic efficacy of somatostatin and
      octreotide in acute pancreatitis and ERCP appears to be related to their
      differential effects on sphincter of Oddi motility--the native hormone relaxing,
      and the analogue increasing, its contractility. Consequently, any beneficial
      effects of octreotide in both acute pancreatitis and ERCP are offset by the
      increased contractility of the sphincter of Oddi, which results in retention of
      activated enzymes within the pancreas and further autodigestion of the gland.
      Somatostatin and octreotide are equally effective in promoting the closure of
      pancreatic fistulae. However, the time to closure after commencement of therapy
      is much more variable and longer in patients treated with subcutaneous octreotide
      than those receiving intravenous somatostatin, possibly as a result of
      fluctuations in pancreatic enzyme secretion between consecutive administrations
      of the hormone. Furthermore, the initial potent inhibitory effect of octreotide
      on pancreatic secretion is lost after 7 days of continuous subcutaneous
      administration. Therefore, in terms of cost-effectiveness, somatostatin would
      appear to be the treatment of choice for pancreatic fistulae. Octreotide markedly
      reduces the complication rates after elective pancreatic surgery. It remains to
      be established whether somatostatin is as effective as octreotide in this
      indication.

PMID- 8527612
TI  - Review article: the continuing development of proton pump inhibitors with
      particular reference to pantoprazole.
AB  - Inhibition of the gastric proton pump is gaining acceptance as the treatment of
      choice for severe gastrooesophageal reflux disease, and for treatment of duodenal
      and gastric ulceration. Three of these drugs are now available (omeprazole,
      lansoprazole and pantoprazole) and more are being developed. Proton pump
      inhibitors share the same core structure, but differ in terms of substituents on
      this core. The substitutions are able to modify some important chemical
      properties of the compounds. For example, pantoprazole is significantly more acid
      stable than omeprazole or lansoprazole. E3810 is significantly less stable than
      the other compounds. We present an explantation for this finding that depends on
      the relative pK values for the pyridine and benzimidazole nitrogens, especially
      the former. Pantoprazole formulated in an enteric-coated tablet displays high
      bioavailability and linear pharmacokinetics whether on single or multiple dose
      regimens. Although all three proton pump inhibitors provide a similar chemical
      conversion to sulphenamides, which are highly reactive cysteine reagents, these
      reagents derivatize different cysteines in the extracytoplasmic or membrane
      domain of the pump and inhibit the pump at different rates. Whereas the
      differences in chemical reactivity can be explained by the solution chemistry of
      the compounds, selective derivatization of different cysteines on the protein
      argues for an involvement of pump structure in response to the presence of the
      proton pump inhibitor on its luminal surface. This suggests that the proton pump
      inhibitors, which were originally designed to take advantage of only the highly
      acidic space generated in the parietal cell by the production of the
      sulphenamide, are made even more selective by the protein they target.
      Pantoprazole is metabolized by a combination of phase I and phase II metabolism,
      and has also been shown to have a very low potential for drug interaction.
      Studies of acid secretion in man have shown this compound to be an effective and
      long lasting inhibitor of acid secretion. The pharmacodynamics explain the
      cumulative effect of repeated doses and maximal acid secretory capacity with a
      once daily dosage.

PMID- 8527613
TI  - Gastric mucosal adaptation to etodolac and naproxen.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently cause damage
      to the gastroduodenal mucosa, principally by suppressing mucosal prostaglandin
      synthesis. However, such acute mucosal injury usually resolves, despite continued
      NSAID administration, by a process known as adaptation. Newer NSAIDs, such as
      etodolac, have been developed to minimize effects on prostaglandin synthesis.
      AIM: To determine whether etodolac causes less acute damage than naproxen, and
      whether the damage produced resolves with continued NSAID administration.
      METHODS: Twenty-four healthy volunteers were given a 28-day course of either
      etodolac 300 mg b.d. or naproxen 500 mg b.d. Gastroduodenal damage was assessed
      using a modified Lanza scoring system and mucosal blood flow with laser doppler
      flowmetry at endoscopy before NSAID administration and during days 1, 7 and 28 of
      continued intake. RESULTS: Maximum gastric damage (median grade and interquartile
      range, IQR) occurred during the first 24 h of administration, being greater with
      naproxen (2.0, IQR 1.0-3.0) than etodolac (1.0, IQR 1.0-1.5; P = 0.03). Such
      damage was associated with a fall in antral blood flow in the naproxen group
      (mean +/- S.E.M.) from 54.5 +/- 3.4 to 43.8 +/- 3.4 arbitrary units (P = 0.07)
      and a slight increase in mucosal blood flow in the etodolac group from 43.5 +/-
      2.24 to 49.5 +/- 3.6 arbitrary units. With continued intake this damage resolved
      in all subjects taking etodolac and in eight of 14 subjects on naproxen.
      Resolution in the naproxen group was associated with a return to normal of antral
      blood flow. CONCLUSIONS: These observations suggest that etodolac causes less
      mucosal damage than naproxen and that adaptation occurs to both.

PMID- 8527614
TI  - Octreotide treatment of carcinoid syndrome: analysis of published dose-titration
      data.
AB  - BACKGROUND: Octreotide has proven therapeutically effective in carcinoid
      syndrome, but the rarity of carcinoid tumors has hampered detailed dose-ranging
      studies. This study analysed published dose-titration data on octreotide use in
      carcinoid patients to (a) investigate the relation between octreotide dose and
      efficacy and (b) establish octreotide dosing recommendations for maximum
      therapeutic benefit. METHOD: An exhaustive, computer-assisted literature search
      for published articles employing octreotide to manage patients with carcinoid
      syndrome was performed using several databases. The relation between octreotide
      dose and efficacy in decreasing urinary 5-hydroxyindoleacetic acid (5-HIAA)
      levels, flushing and diarrhoea was analysed for seven dose ranges by pooling data
      from selected articles. RESULTS: Analysis of data compiled from 62 published
      studies revealed that maximum effective therapeutic doses of octreotide
      effectively controlled symptoms in up to 93% of patients, and that increasing the
      dose of octreotide is associated with increased benefit with respect to control
      of flushing, diarrhoea and 5-HIAA levels. CONCLUSIONS: We recommend starting
      octreotide therapy at 100 micrograms subcutaneously t.d.s. in patients with
      mild/moderate, non-life-threatening carcinoid syndrome. Since therapeutic
      response to octreotide varies markedly among patients, we recommend titrating the
      octreotide dose in increments of 50-100 micrograms every 8 h until adequate
      symptom control is achieved.

PMID- 8527615
TI  - Low dose famotidine in the prevention of sleep disturbance caused by heartburn
      after an evening meal.
AB  - AIM: To determine whether, in a susceptible population, dosing with 10 mg
      famotidine 1 h before an evening meal could decrease the interference with sleep
      caused by heartburn. METHODS: Patients with a history of frequent heartburn (n =
      309) were randomized to receive 10 mg famotidine or placebo 1 h before an evening
      meal likely to induce symptoms. Patients assessed the efficacy of the treatment
      in preventing heartburn after the meal, at bedtime and during the night. The
      number of awakenings due to heartburn and the consumption of antacid tablets
      taken to alleviate symptoms were also recorded. RESULTS: Treatment groups were
      well matched and data from 302 patients were available for analysis. Compared to
      placebo, famotidine treated patients had: less heartburn after the meal (P <
      0.0001 mean global scores), less interference with getting to sleep (P = 0.0156
      mean global scores), fewer awakenings (P = 0.0001 difference in mean number) and
      better control of heartburn during the night (P < 0.0001 mean global scores).
      They were also almost three times less likely to need antacid treatment than the
      placebo group during the night (relative odds for no antacid 2.78 (95% CI: 1.29
      5.96). Only four patients in each group suffered adverse events. CONCLUSION:
      Taking a 10 mg dose of famotidine 1 h before an evening meal appears to be a
      successful and well tolerated strategy for preventing post-prandial heartburn and
      avoiding the associated interference with sleep.

PMID- 8527616
TI  - Intestinal site-dependent susceptibility to chronic indomethacin in the rat: a
      morphological and biochemical study.
AB  - BACKGROUND: The cyclo-oxygenase inhibitor indomethacin induces a pattern of
      gastrointestinal injury in the rat that is site-dependent. This study compared
      the extent of injury to different regions of the rat intestine (small intestine,
      caecum and colon) with the corresponding changes in arachidonic acid metabolism
      in these areas, following long-term, low-dose indomethachin. METHODS: Rats (eight
      per group) received either indomethacin (3 mg.kg/day) or control diet for either
      6 or 12 weeks. At termination animals were bled, examined both macroscopically
      and microscopically for ulcers, and assayed for blood thromboxane B2, intestinal
      tissue prostaglandin E2 content and production of leukotriene B4. In a further
      eight animals luminal indomethacin concentrations from the small intestine,
      caecum and colon were measured following 6 weeks of chronic drug ingestion.
      RESULTS: At 6 weeks, macroscopic ulcers were observed in 2/8 (small intestine),
      3/8 (caecum) and 1/8 (colon) animals. The corresponding ratios at 12 weeks were
      5/8, 8/8 and 0/8. In control animals, a site-dependent gradient of the
      prostaglandin E2 concentration was found. In indomethacin-dosed animals the
      intestinal prostaglandin E2 content was reduced significantly in the caecum at 6
      weeks, and in all tissues at 12 weeks. An increased leukotriene B4 production was
      observed in the caecum only, at 12 weeks (P < 0.01), and the blood thromboxane B2
      was reduced at both time points (P < 0.05). CONCLUSION: There is a site-dependent
      gradient of the prostaglandin E2 concentration in the rat intestine. The rat
      caecum is particularly sensitive to long-term low-dose indomethacin, both in
      terms of chronic intestinal inflammation and changes in prostanoid metabolism.
      This site-dependent degree of injury may be associated with a local cyclo
      oxygenase inhibition.

PMID- 8527617
TI  - Comparison of pantoprazole versus omeprazole in the treatment of acute duodenal
      ulceration--a multicentre study.
AB  - METHODS: In this randomized, double-blind, multicentre study, the proton pump
      inhibitors pantoprazole and omeprazole were compared in patients with active
      duodenal ulcers. Two hundred and seventy-six protocol-correct patients received
      either pantoprazole 40 mg (n = 185) or omeprazole 20 mg (n = 91), once daily for
      2 or 4 weeks, depending on the progress of ulcer healing. RESULTS: Rates of
      complete ulcer healing after 2 weeks were 71% in patients given pantoprazole and
      74% in patients given omeprazole. After 4 weeks the figures were 96% and 91%,
      respectively. These differences were not significant. There was no significant
      difference in ulcer pain prior to treatment, and 85% of the pantoprazole group
      and 86% on omeprazole were pain-free after 2 weeks (not significant). The time
      until complete pain relief with pantoprazole or omeprazole, based on data from
      diary cards, was not significantly different (P > 0.05, Uleman's U-test). Both
      treatments were equally well tolerated. Changes in routine laboratory parameters
      were minimal in both groups. CONCLUSION: Pantoprazole was shown to be a highly
      effective and well-tolerated treatment for acute duodenal ulcer. Pantoprazole 40
      mg and omeprazole 20 mg were equally effective with respect to ulcer healing and
      pain relief, and have similar adverse event profiles.

PMID- 8527618
TI  - Eradication of Helicobacter pylori and prevention of recurrence of duodenal
      ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or
      without clarithromycin.
AB  - BACKGROUND: Antimicrobial treatment for Helicobacter pylori eradication is
      currently recommended for all patients with duodenal ulcer disease, but consensus
      on the best treatment is lacking. METHODS: Patients with active duodenal ulcer
      and H. pylori were enrolled in a double-blind, randomized, placebo-controlled
      multi-centre study. Patients received omeprazole 40 mg daily for 28 days and
      either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days.
      Patients underwent endoscopy before starting treatment, at 2 weeks, immediately
      after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after
      the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori,
      duodenal ulcer healing and ulcer recurrence were measured. RESULTS: One-hundred
      and fifty-four patients were recruited and randomized to omeprazole plus
      clarithromycin (n = 74) or to omeprazole plus placebo (n = 80). One month after
      treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72-91%) patients
      receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0
      7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus
      clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71-91%) and at 4 weeks
      in 100% (95% CI: 95-100%), compared with 77% (95% CI: 66-86%) and 97% (95% CI: 91
      100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months
      in 6% (95% CI: 1-16%) of patients given omeprazole plus clarithromycin, compared
      with 76% (95% CI: 63-86%) of patients given omeprazole plus placebo (P < 0.001).
      The incidence of side-effects was similar in both treatment groups (38% with
      clarithromycin dual therapy and 29% with omeprazole plus placebo; P = 0.304).
      Ninety per cent of patients took at least 90% of their prescribed medication.
      CONCLUSIONS: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in
      83% of patients with duodenal ulcer and significantly decreased 12-month
      recurrence from 76% to 6%.

PMID- 8527619
TI  - Double-blind, randomized trial of roxatidine 150 mg in the early evening versus
      bedtime administration in the short-term treatment of duodenal ulcer.
AB  - AIM: To compare the efficacy and tolerability of early evening (19.00-21.00
      hours) vs. bedtime (22.00-00.00 hours) oral administration of roxatidine 150 mg
      in the short-term treatment of active duodenal ulcer. METHODS: The trial was
      randomized, double-blind and double-dummy, with parallel groups. A total of 276
      patients were recruited and randomly assigned either to roxatidine in the early
      evening (n = 139) or roxatidine at bedtime (n = 137). RESULTS: After 4 weeks, 78%
      of patients receiving roxatidine in the early evening and 74% of those treated at
      bedtime had achieved complete healing, as determined by per-protocol analysis.
      With intention-to-treat analysis the healing rates were 70.5% and 70.8%,
      respectively. After 8 weeks the healing rates in the early evening and bedtime
      treatment groups were 92% and 95% (per-protocol analysis) and 78% and 84%
      (intention-to-treat analysis). Both treatments proved effective in reducing the
      frequency and severity of daytime and nocturnal epigastric pain, as well as other
      ulcer-related symptoms. CONCLUSIONS: This study confirmed the healing and
      analgesic properties of roxatidine in duodenal ulcer disease. Early evening or
      bedtime dosing with roxatidine 150 mg resulted in similar 4- to 8-week rates of
      duodenal ulcer healing.

PMID- 8527620
TI  - Pain and quality of life in patients with acute duodenal ulcer treated with
      ranitidine.
AB  - BACKGROUND: The various components of pain and quality of life in duodenal ulcer
      patients receiving antisecretory drugs have not been studied to date. METHODS:
      Ninety-five patients with epigastric pain and duodenal ulcer at endoscopy
      completed this prospective, multicenter, open-study. All were treated with
      effervescent ranitidine 300 mg daily for 4 weeks. The following parameters were
      assessed: (a) disappearance of duodenal ulcer pain by self-evaluation and on a
      weekly visual analogue scale (VAS) from 0 to 100; (b) evolution of sensory and
      affective components of ulcer pain by the Validated French Version of the McGill
      Pain Questionnaire (Questionnaire Douleur de Saint-Antoine, QDSA); (c) quality of
      life by the Nottingham Health Profile (NHP) which includes six criteria: pain,
      mobility, energy, emotions, sleep and social isolation. RESULTS: Forty-nine, 66
      and 87% of the patients were pain-free during the day-time after 7, 14 and 28
      days, respectively. Corresponding figures for the night-time were 80%, 88% and
      97% respectively. Median time to disappearance of ulcer pain was 8 days. VAS self
      assessment showed a significant decrease each week throughout the treatment
      period (P = 0.001). Sensory and affective QDSA scores were significantly improved
      after the second day and at each assessment during the 28 days of treatment (P =
      0.001). Physical as well as affective aspects of quality of life were
      significantly improved after 28 days for each of the six criteria explored (P =
      0.001). The duodenal ulcer healing rate was 86% after 4 weeks of treatment.
      CONCLUSIONS: Using complementary scales measuring different aspects of ulcer
      pain, sensory and affective components improved significantly from the second day
      of treatment with ranitidine 300 mg. A significant improvement in quality of life
      is observed after a 4-week treatment. QDSA and NHP appear to be useful evaluation
      tools of duodenal ulcer pain and quality of life.

PMID- 8527621
TI  - Loperamide oxide in acute diarrhoea: a double-blind, placebo-controlled trial.
      The Dutch Diarrhoea Trialists Group.
AB  - BACKGROUND: Loperamide is an established treatment of acute diarrhoea with only
      rare adverse reactions. The pro-drug loperamide oxide is converted to loperamide
      by anaerobic bacteria in the lower alimentary tract. With the use of loperamide
      oxide, it was expected to obtain similar antidiarrhoeal efficacy as with
      loperamide, but with a lower dose and a lower plasma concentration. The incidence
      of adverse reactions might be reduced with the use of loperamide oxide. METHODS:
      Loperamide oxide (0.5 and 1 mg capsules) was compared with placebo in a double
      blind treatment of acute diarrhoea of 242 patients. Relief of diarrhoea was
      significantly more rapid for either dose of loperamide oxide than for placebo.
      Both the investigators' and the patients' global assessment of the treatment
      significantly favoured the loperamide oxide 1 mg capsule, but not 0.5 mg, over
      placebo. Adverse experiences were less frequent in the drug-treated than in the
      placebo-treated group. CONCLUSION: These results suggest that loperamide oxide 1
      mg produces effective relief of diarrhoeal symptoms.

PMID- 8527622
TI  - Gastric persorption of bismuth from ranitidine bismuth citrate.
AB  - AIM: To determine whether bismuth penetrates the gastric mucosa after dosing with
      ranitidine bismuth citrate. METHODS: Twelve patients presenting with dyspepsia
      were randomized to receive either ranitidine bismuth citrate or placebo, 20-40
      min prior to endoscopy. Biopsies were taken from four sites during endoscopy: the
      first and second parts of the duodenum, the antrum, and the body of the stomach.
      Biopsies were analysed by electron microscopy and X-ray microanalysis. RESULTS:
      Bismuth particles were found to be interposed between epithelial cells in the
      antral mucosa of three of eight patients who were dosed with ranitidine bismuth
      citrate. Columns of bismuth particles could be tracked down the lamina propria
      and were seen to be surrounding blood vessels. Bismuth particles were observed in
      the inter- and intra-cellular channels of the endothelial cells of the blood
      vessels in the lamina propria and also close to the luminal surface of the
      endothelial cell. This process of persorption was similar to that described in a
      previous report of electron microscopy appearances of the gastric antrum after
      dosing with tripotassium dicitrato bismuthate, but was quantifiably smaller and
      not observed in all the patients dosed with ranitidine bismuth citrate. No
      penetration of the mucosa by bismuth particles was seen in the body of the
      stomach or the duodenum. CONCLUSION: Penetration of bismuth particles into the
      gastric mucosa may occur after oral dosing with ranitidine bismuth citrate.

PMID- 8527623
TI  - Long term continuous omeprazole treatment of patients with Barrett's oesophagus.
AB  - BACKGROUND: The metaplastic columnar epithelium in Barrett's oesophagus has
      malignant potential. AIM: To determine whether decreasing acid reflux leads to
      regression of Barrett's epithelium. METHOD: Twenty-four patients with Barrett's
      oesophagus were treated with omeprazole 20 mg o.m. in an open, prospective study;
      11 were treated for 12 months, and 13 for 24 months. Another group of 17 patients
      with Barrett's oesophagus was treated with an H2-receptor antagonist in standard
      dosage for 12-36 (mean 23) months. Patients were assessed endoscopically.
      RESULTS: No evidence of significant shortening of the length of Barrett's
      oesophagus was seen in any patient treated for 12 or 24 months with omeprazole.
      Similarly, no shortening of the length of Barrett's oesophagus was seen in any
      patient treated with an H2-receptor antagonist. However, 6 of 11 patients treated
      with omeprazole for 12 months, and 7 of 13 treated for 24 months, developed
      macroscopic squamous islands visible below the squamo-columnar junction. This was
      not seen in any patient treated with an H2-receptor antagonist. CONCLUSION:
      Although there can be reappearance of squamous epithelium in Barrett's oesophagus
      of some patients during treatment with omeprazole 20 mg o.m. over 12-24 months, a
      significant shortening of the columnar lined segment is not seen.

PMID- 8527624
TI  - Steroid treatment in active Crohn's disease: a comparison between two regimens of
      different duration.

PMID- 8527625
TI  - [Heart rate: a variable that is easy to measure and provides information on
      cardiovascular risk].

PMID- 8527626
TI  - [Comparative study on the influence of health education on perceived recurrences
      after physiotherapy].
AB  - OBJECTIVE: To compare the repercussion on requests for follow-up treatment of the
      inclusion of health education in the physiotherapist's primary care work.
      SETTING: Health centre (A). Hospital (B). PATIENTS AND INTERVENTION: Patients
      attending over a six month period two physiotherapy units due to back-ache,
      cervical pain or a painful shoulder. Group A had 50 patients; and B, 97. The
      groups were homogeneous by age and gender: A averaged 47 years old (+ 13.4) and
      was 64% women; B was 45 (+ 12.1) and 69% women. The percentage of pathologies was
      also homogeneous with a p > 0.1 in back-ache and cervical pain and p > 0.90 for
      painful shoulders. At centre B (catchment population 73,000) individualised
      therapy (electrotherapy) was used. At A (catchment 16,000) there was a complete
      intervention plus health education. A monitoring period for the six following
      months was set up to observe, for both groups, the number of people who requested
      Physiotherapy for the same pathology. MEASUREMENTS AND MAIN RESULTS: A
      statistical analysis contrasting equality of proportions by analysing contingency
      tables with the Chi2 test was performed. During the monitoring period five new
      treatments in group A (10%) and 29 in B (30%) were requested, which meant a
      significant difference between the two groups with a p < 0.01 confirmed by an
      analysis of remainders. CONCLUSIONS: Incorporating health education into the
      Physiotherapist's activities provided in the medium term fewer requests from
      relapsed patients. It would be interesting to perform longer studies to check if
      these differences last.

PMID- 8527627
TI  - [Evolution of pregnancy in adolescents of Catalonia (1987-1992)].
AB  - OBJECTIVE: To analyse the evolution of both pregnancies and voluntary
      terminations among adolescent women living in Catalonia. DESIGN: An observational
      crossover study. SETTING: Catalonia. PATIENTS AND OTHER PARTICIPANTS: The rates
      of fertility, pregnancy and voluntary termination (VT) were calculated. The ratio
      of VT per 100 live births among adolescent women (aged 15 to 19) and among the
      general population (15 to 49) between 1987 and 1992 was also calculated.
      MEASUREMENTS AND MAIN RESULTS: The pregnancy rate of adolescents remained stable
      throughout the study period, whereas their fertility rate went down. In parallel
      there was a spectacular increase in the percentage of VTs per live birth among
      adolescents. CONCLUSIONS: Since the pregnancy rate among adolescents remained
      practically stable throughout the study period, an increase in activities aimed
      at primary prevention of these pregnancies is recommended.

PMID- 8527628
TI  - [Analysis of the variability of primary care costs].
AB  - OBJECTIVE: To find the costs of Primary Care services and centres and identify
      the variables which enable the possible differences between them to be explained.
      DESIGN: Cost analysis study. SETTING: Primary Care Centres. PARTICIPANTS: 15
      Primary Care Centres managed by the Catalan Health Institute. MEASUREMENTS AND
      MAIN RESULTS: Costs of chapters 1 (staff), 11 (running costs) and 1V (medicines)
      of the accounts for the 1993 exercise and possible cost variability between
      services and Health Centres were analysed. The cost per inhabitant of services
      was, in order of importance: general medicine (18,873 pesetas per inhabitant),
      Paediatrics (16,204), Odontology (638) and Social Work (255). The mean cost of
      Primary Care Centres was 19,137 pesetas per inhabitant. The variables which
      seemed to explain variability of operating costs were: for general medicine, the
      inhabitant to doctor ratio (r2 0.31, p < 0.02); for Paediatrics, the number of
      attendances (r2 0.35, p < 0.01); and for health centres, the inhabitant to doctor
      ratio, teaching and number of attendances (r2 0.75, p < 0.001). CONCLUSIONS: The
      analysis of costs of services and centres enables us to identify and compare
      results between different suppliers, which can be useful when we need parameters
      to measure efficiency.

PMID- 8527629
TI  - [Sources of information about cancer].
AB  - OBJECTIVE: To study the present and preferred sources of information about
      cancer. DESIGN: Cross-sectional study. PLACE: Counties of Girones and Pla de
      l'Estany from the province of Girona. PARTICIPANTS: Stratified random sample of
      408 women aged 40 to 70 years. RESULTS: Main present source of information about
      cancer were friends and relatives (34.9%), followed by radio and Tv (34.0%) and
      newspapers (19.9%). Health care professionals only were considered main source of
      information by 11.3% of the sample. Women with incomplete primary school and
      women from older age groups answered more frequently Radio and Tv as their main
      source of information. However, the preferred source of information about cancer
      were health care professionals (73.3%). CONCLUSION: Health care professionals are
      the preferred source of information about cancer but only a small percentage of
      population receive information from them. These results indicate the need to
      redefine educational strategies regarding cancer in primary health care.

PMID- 8527630
TI  - [User satisfaction with primary care teams: related to doctor's training in the
      field of physician-patient relations].
AB  - OBJECTIVE: To find the satisfaction level of health users attended by Bizkaia
      primary care teams (PCT) with 5 or more permanent doctors and to determine
      whether there is any relationship between satisfaction and doctors being trained
      in doctor-patient relationships (DPR). SETTING: Primary Care. Towns in the 2
      health areas out of the 6 in which Bizkaia is divided. PARTICIPANTS:  TARGET
      POPULATION: the users of PCTs with 5 or more doctors in the 2 health areas. The
      randomly selected sample had 323 patients, to which we had earlier added 30% (n =
      420) due to the probable non-repliers. INTERVENTION AND RESULTS: Satisfaction was
      measured using the questionnaire composed by J.M. Moreno et al; and training in
      DPR, using a questionnaire composed by the authors. Satisfaction scored on
      average 73 points out of 80 (range 34 to 80). 36.7% of the doctors had low or nil
      training in DPR (< 10 hours); 16.7% had average training (10 to 40 hours); and
      46.7% stated they had a high level of training (> 40 hours). Data analysis showed
      that satisfaction increased in line with the user's age and the length of the
      user's relationship with the doctor. CONCLUSIONS: 1) The satisfaction found is
      high, which corroborates other authors' results. 2) The most determinant variable
      of user satisfaction is age. 3) We found no statistically significant association
      between patient satisfaction and doctor training in the field of DPR.

PMID- 8527631
TI  - [Taeniasis and primary care].
AB  - OBJECTIVE: To evaluate the therapeutic guidelines used in evaluating taeniasis in
      primary care (mebendazole, pyrantel pamoate) and to show the low availability of
      first choice drugs (niclosamide, praziquantel). DESIGN: A retrospective,
      descriptive study. SETTING: A clinic for travellers abroad in the Tropical
      Medicine section (Infectious Diseases Service) of the Hospital Clinic, Barcelona.
      PARTICIPANTS: 68 medical histories of cases of Taeniasis seen at this clinic
      between 1984 and 1994. RESULTS: 72.3% had not travelled to the tropics
      (autochthonous Taeniasis). The most common symptoms were epigastralgia, anal
      pruritus, diarrhoea, weight loss and bulimia. 71.2% had previously attended other
      medical services and all had been correctly diagnosed. 91.8% had received
      ineffective treatment (the most common treatment was with mebendazole and
      pyrantel pamoate), sometimes on different occasions. Time elapsed between
      diagnosis and correct treatment varied from 1 day to 36 months. CONCLUSION:
      Taeniasis is an easily diagnosed infestation. Its treatment is comfortable and
      effective, with an average cure period of 24 hours. However, the particular
      medicines are not available in primary care, which hampers and delays treatment.

PMID- 8527632
TI  - [Therapeutic observance in arterial hypertension. Reliability of indirect methods
      assessing therapeutic compliance].
AB  - OBJECTIVE: To validate six indirect methods which evaluate observance of therapy
      for arterial hypertension (AHT). DESIGN: Prospective study. SETTING: Urban health
      centre, Huelva. PATIENTS: 90 individuals (25 men and 65 women) (average age 59.2
      +/- 11) chosen at random from the AHT clinic. MEASUREMENTS AND MAIN RESULTS: Home
      based survey and review of clinical records. We counted hypotensive tablets at
      the start of the study and after a month. The indirect methods studied were: Self
      communicated compliance (SC), attendance for appointments (AA), control of
      arterial pressure (CP), Morinsky-Green test (MG), knowledge of the illness (KI)
      and medical opinion (MO). We used the counting of tablets as the standard method.
      We studied the prevalence of non-observance, validity (2 x 2 table) and the
      concordance of the different methods. Prevalence of non-compliance was 16.7% (p =
      NS for age and gender). The average Systolic AP and Diastolic AP of compliers and
      non-compliers were 137 and 147 mmHg (p < 0.035) and 83 and 90 mmHg (p < 0.006),
      respectively. CONCLUSIONS: We found a high level of compliance. The SC
      underestimated non-compliance, which was overestimated by the other methods. We
      recommend SC and MO for detecting the non-complier, as they have greater
      specificity and better positive predictive values; and KI for detecting the
      complier, as it has greater sensitivity and negative predictive value. However
      these conclusions should be treated cautiously, since concordance of the
      different tests regarding the counting of tablets is weak.

PMID- 8527633
TI  - [Characterization of the assistance work of the general/family physician].

PMID- 8527634
TI  - [Acarbia and digoxin].

PMID- 8527635
TI  - [Breast feeding and prevention of Haemophilus meningitis].

PMID- 8527636
TI  - [Herpes zoster in primary care].

PMID- 8527637
TI  - [Drug advertising].

PMID- 8527638
TI  - [Computer-controlled laser irradiation unit for studies of light-induced
      processes in cell cultures].
AB  - For the photodynamic treatment of tumours, synergistic effects of
      photosensitizing substances and light (today usually laser light) are used. With
      the aim of optimizing photosensitizing drugs and therapy, the effects of light
      and drug dose were studied in cell experiments. To automate and standardize such
      in vitro experiments, a laser irradiation chamber was developed. Cells cultured
      from tumour cell lines are placed on micro-titre plates or in petri dishes,
      together with the photosensitizer, and subsequently irradiated in the irradiation
      chamber with a well-defined dose of laser light of a wavelength corresponding to
      the absorbance of the photosensitizing agent. The plates or dishes are irradiated
      from below. In this way, light dose errors due to refraction from the meniscus of
      the cell suspension as occurs with irradiation from above, are avoided. During
      irradiation, speckle effects on the underside of the plates or petri dishes lead
      to variation in irradiation. A vibrator keeps the light transmission fibre and
      thus speckle pattern in motion, guaranteeing a homogeneous irradiation of the
      cells.

PMID- 8527639
TI  - [Testing methods for the characterization of catheter balloons and lumina].
AB  - The present paper reports on the characterization of catheter balloons and lumina
      on the basis of such known parameters as residual volume, compliance, burst
      pressure and flow rate, with the aim of developing standards, test methods and
      testing equipment as well as standards. These are becoming ever more important
      with the coming into force of the EC directive on medical products [7] and the
      law governing medical products in Germany [13], which requires manufacturers to
      specify the properties of their products. Our testing concept is based on a
      commercially available machine that subjects materials to alternating extension
      and compression forces over the long-term, to which we added a special hydraulic
      module. Using the multimedia technology we achieved a real time superimposition
      of the volume-diameter curve on the balloon. The function of the testing device
      and method is demonstrated on dilatation catheters. Our initial results reveal
      compatibility with the requirements of the 1% accuracy class. Use of this
      methodology for comparative testing of catheters and quality evaluation is
      recommended.

PMID- 8527640
TI  - [Effect of background flow on the accuracy of respiratory flow and respiratory
      volume measurement in newborn infants].
AB  - Measurement of ventilation, in particular in preterm infants, is greatly impaired
      by equipment dead space, with its significant effect on the ventilatory pattern
      and gas exchange. For patients of this age, therefore, dead-spacefree methods are
      needed for long-term measurements. Rebreathing can be avoided if the
      pneumotachograph (PNT) and face mask are flushed with a continuous background
      flow. The effect of this on the measurements has not yet been investigated in
      detail. A measuring system comprising two identical baby PNTs (Jaeger/Germany)
      permitting a background flow of between 0 and 7 l per min was used. Spontaneous
      breathing was simulated with a 100 ml calibration syringe employing volumes of
      20, 40, 60 and 100 ml (Rudolph/USA) and a frequency of 30 min-1. The measurements
      were carried out with a T-piece from a respirator circuit, a hand mask (50 ml)
      and a face chamber having a volume of 850 ml (Siemens-Elema/Sweden). To
      investigate the dynamic properties of the equipment, we employed flow jumps
      generated with a magnetic valve (response time < 2 ms) and analysed the responses
      using Fourier analysis. We were unable to find any significant relationship
      between the accuracy of volume measurement and tidal volume for any of the
      measured volumes. An increase in background flow resulted in an underestimation
      of the volume with an error < 3%. We found no influence of the background flow or
      type of face mask on the frequency response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527641
TI  - [Animal experiment study of titanium with surface coatings of (Ti,Nb)ON and
      (Ti,Zr)O].
AB  - Titanium is considered to be biocompatible as long as the passive layer of TiO2
      which is formed within the body, is not destroyed mechanically by the shearing
      forces acting on implants during function. Mechanically stable hard coatings on
      the basis of the so-called refractory metals render titanium wear-and-tear
      resistant, with the added advantage for its biocompatibility of keeping its the
      physical and electrochemical properties constant, even in the event of relative
      movement against hard or soft tissue. Biological testing of coated and uncoated
      titanium in experimental animals shows that the deposition of new bone on
      (Ti,Zr)O or (Ti,Nb)ON surfaces takes place in the same way as on the surface of
      titanium.

PMID- 8527642
TI  - [Effects of different sterilization procedures on degree of oxidation of ultra
      high molecular weight polyethylene].
AB  - We investigated the influence of different sterilization techniques on the degree
      of oxidation of UHMWPE. Oxidation effects were documented by infrared
      spectroscopy. The UHMWPE was sterilized with the aid of gamma radiation (2.5
      Mrad) in air, gamma radiation in argon, ethylene oxide and autoclaving. Non
      sterilized UHMWPE served as control material. The results showed significant
      differences for the various sterilization techniques employed. The highest degree
      of oxidation was seen after autoclaving, but gamma radiation was also associated
      with a significant degree of oxidation. Using gamma radiation in argon, the
      degree of oxidation was significantly reduced. Following sterilization with
      ethylene oxide, no oxidation was to be found. In view of these facts, UHMWPE
      should be sterilized only with ethylene oxide or with gamma radiation in argon.

PMID- 8527643
TI  - Fluorescence imaging of local membrane electric fields during the excitation of
      single neurons in culture.
AB  - The spatial distribution of depolarized patches of membrane during the excitation
      of single neurons in culture has been recorded with a high spatial resolution (1
      micron2/pixel) imaging system based on a liquid-nitrogen-cooled astronomical
      camera mounted on an inverted microscope. Images were captured from rat nodose
      neurons stained with the voltage-sensitive dye RH237. Conventional intracellular
      microelectrode recordings were made in synchrony with the images. During an
      action potential the fluorescence changes occurred in localized, unevenly
      distributed membrane areas, which formed clusters of depolarized sites of
      different sizes and intensities. When fast conductances were blocked by the
      addition of tetrodotoxin, a reduction in the number and the intensities of the
      depolarized sites was observed. The blockade by tetrodotoxin of voltage-clamped
      neurons also reduced the number of depolarized sites, although the same
      depolarizing voltage step was applied. Similarly, when a voltage-clamped neuron
      was depolarized by a constant-amplitude voltage step, the number of depolarized
      sites varied according to the degree of activation of the voltage-sensitive
      channels, which was modified by changing the holding potential. These results
      suggest that the spatial patterns of depolarization observed during excitation
      are related to the operations of ionic channels in the membrane.

PMID- 8527644
TI  - Electronic structure of Q-A in reaction centers from Rhodobacter sphaeroides. I.
      Electron paramagnetic resonance in single crystals.
AB  - The magnitude and orientation of the electronic g-tensor of the primary electron
      acceptor quinone radical anion, Q-A, has been determined in single crystals of
      zinc-substituted reaction centers of Rhodobacter sphaeroides R-26 at 275 K and at
      80 K. To obtain high spectral resolution, EPR experiments were performed at 35
      GHz and the native ubiquinone-10 (UQ10) in the reaction center was replaced by
      fully deuterated UQ10. The principal values and the direction cosines of the g
      tensor axes with respect to the crystal axes a, b, c were determined. Freezing of
      the single crystals resulted in only minor changes in magnitude and orientation
      of the g-tensor. The orientation of Q-A as determined by the g-tensor axes
      deviates only by a few degrees (< or = 8 degrees) from the orientation of the
      neutral QA obtained from an average of four different x-ray structures of Rb.
      sphaeroides reaction centers. This deviation lies within the accuracy of the x
      ray structure determinations. The g-tensor values measured in single crystals
      agree well with those in frozen solutions. Variations in g-values between Q-A, Q
      B, and UQ10 radical ion in frozen solutions were observed and attributed to
      different environments.

PMID- 8527645
TI  - Real time imaging of single fluorophores on moving actin with an epifluorescence
      microscope.
AB  - Relatively simple modifications of an ordinary epifluorescence microscope have
      greatly reduced its background luminescence, allowing continuous and real time
      imaging of single fluorophores in an aqueous medium. Main modifications were
      changing the excitation light path and setting an aperture stop so that stray
      light does not scatter inside the microscope. A simple and accurate method using
      actin filaments is presented to establish the singularity of the observed
      fluorophores. It was possible, at the video rate of 30 frames/s, to image
      individual tetramethylrhodamine fluorophores bound to actin filaments sliding
      over heavy meromyosin. The successful imaging of moving fluorophores demonstrates
      that conventional microscopes may become a routine tool for studying dynamic
      interactions among individual biomolecules in physiological environments.

PMID- 8527646
TI  - On the pH dependence of amide proton exchange rates in proteins.
AB  - We have analyzed the pH dependencies of published amide proton exchange rates
      (kex) in three proteins: bovine pancreatic trypsin inhibitor (BPTI), bull seminal
      plasma proteinase inhibitor IIA (BUSI IIA), and calbindin D9K. The base-catalyzed
      exchange rate constants (kOH) of solvent exposed amides in BPTI are lower for
      residues with low peptide carbonyl exposure, showing that the environment around
      the carbonyl oxygen influences kOH. We also examined the possible importance of
      an exchange mechanism that involves formations of imidic acid intermediates along
      chains of hydrogen-bonded peptides in the three proteins. By invoking this
      "relayed imidic acid exchange mechanism," which should be essentially acid
      catalyzed, we can explain the surprisingly high pHmin (the pH value at which kex
      reaches a minimum) found for the non-hydrogen-bonded amide protons in the beta
      sheet in BPTI. The successive increase of pHmin along a chain of hydrogen-bonded
      peptides from the free amide to the free carbonyl, observed in BPTI, can be
      explained as an increasing contribution of the proposed mechanism in this
      direction of the chain. For BUSI IIA (pH 4-5) and calbindin D9K (pH 6-7) the
      majority of amide protons with negative pH dependence of kex are located in
      chains of hydrogen-bonded peptides; this situation is shown to be consistent with
      the proposed mechanism.

PMID- 8527647
TI  - A genetic algorithm that seeks native states of peptides and proteins.
AB  - We describe a computer algorithm to predict native structures of proteins and
      peptides from their primary sequences, their known native radii of gyration, and
      their known disulfide bonding patterns, starting from random conformations.
      Proteins are represented as simplified real-space main chains with single-bead
      side chains. Nonlocal interactions are taken from structural database-derived
      statistical potentials, as in an earlier treatment. Local interactions are taken
      from simulations of (phi, psi) energy surfaces for each amino acid generated
      using the Biosym Discover program. Conformational searching is done by a genetic
      algorithm-based method. Reasonable structures are obtained for melittin (a 26
      mer), avian pancreatic polypeptide inhibitor (a 36-mer), crambin (a 46-mer),
      apamin (an 18-mer), tachyplesin (a 17-mer), C-peptide of ribonuclease A (a 13
      mer), and four different designed helical peptides. A hydrogen bond interaction
      was tested and found to be generally unnecessary for helical peptides, but it
      helps fold some sheet regions in these structures. For the few longer chains we
      tested, the method appears not to converge. In those cases, it appears to recover
      native-like secondary structures, but gets incorrect tertiary folds.

PMID- 8527648
TI  - A microscopic model of enzyme kinetics.
AB  - Many in vivo enzymatic processes, such as those of the tissue factor pathway of
      blood coagulation, occur in environments with facilitated substrate delivery or
      enzymes bound to cellular or lipid surfaces, which are quite different from the
      ideal fluid environment for which the Michaelis-Menten equation was derived. To
      describe the kinetics of such reactions, we propose a microscopic model that
      focuses on the kinetics of a single-enzyme molecule. This model provides the
      foundation for macroscopic models of the system kinetics of reactions occurring
      in both ideal and nonideal environments. For ideal reaction systems, the
      corresponding macroscopic models thus derived are consistent with the Michaelis
      Menten equation. It is shown that the apparent Km is in fact a function of the
      mechanism of substrate delivery and should be interpreted as the substrate level
      at which the enzyme vacancy time equals the residence time of ES-complexes; it is
      suggested that our microscopic model parameters characterize more accurately an
      enzyme and its catalytic efficiency than does the classical Km. This model can
      also be incorporated into computer simulations of more complex reactions as an
      alternative to explicit analytical formulation of a macroscopic model.

PMID- 8527649
TI  - Surface-mediated enzymatic reactions: simulations of tissue factor activation of
      factor X on a lipid surface.
AB  - Blood coagulation proceeds via reactions in which zymogen coagulation factors are
      activated to proteases. An essential step is the activation of factor X by a
      complex of tissue factor and factor VIIa. This complex usually is studied using
      phospholipid vesicles into which tissue factor is inserted. Because factor X
      exists free in solution and bound to the lipid-surface, it is difficult to
      establish experimentally the kinetic contribution of surfaces. We therefore
      developed a stochastic model to simulate such reactions and generate initial
      velocity data from which Michaelis-Menten parameters are estimated. Simulated Km
      values decrease slightly when substrate binding to lipid is increased and by a
      factor of four when the rates of surface diffusion are increased to that of fluid
      phase-diffusion. Simulations with various size planar surfaces established an
      enzyme capture radius of 32-64 nm. Simulations with different modes of enzyme
      substrate complex assembly show that if the true substrate is lipid-bound, under
      certain conditions, the true Kcat is not measured; rather, the product "leaving
      rate" from the complex is the rate-limiting step that is measured as substrate is
      taken to infinity. This model is applicable to any surface-bound enzyme reaction.

PMID- 8527650
TI  - Barrier-free paths of directed protein motion in the erythrocyte plasma membrane.
AB  - A model is presented for the steric interaction between a plasma membrane protein
      and the membrane cytoskeleton in the human erythrocyte. The cytoskeleton is
      treated as a network of polymer chains attached to a flat bilayer, and the
      membrane protein is a hemisphere of effective radius R(e) with center on the
      bilayer edge. The simulation is used to investigate the barrier-free path L for
      linear guided motion of a protein in the bilayer plane. It is shown that the
      barrier-free paths of small proteins can be used to extract the effective in
      plane diameter of cytoskeletal components. For example, the in-plane diameter of
      an ankyrin attachment site is found to be approximately 12 nm in the simulation,
      or twice the computational spectrin diameter. The barrier-free paths of large
      proteins (R(e) > 23 nm) vanish when the proteins are corralled by the
      cytoskeleton. For intermediate size proteins, L decreases approximately as L is
      directly proportional to S-1.4 where S is proportional to the sum of the protein
      and cytoskeleton chain radii.

PMID- 8527651
TI  - Evaluation of the counterion condensation theory of polyelectrolytes.
AB  - We compare free energies of counterion distributions in polyelectrolyte solutions
      predicted from the cylindrical Poisson-Boltzmann (PB) model and from the
      counterion condensation theories of Manning: CC1 (Manning, 1969a, b), which
      assumes an infinitely thin region of condensed counterions, and CC2 (Manning,
      1977), which assumes a region of finite thickness. We consider rods of finite
      radius with the linear charge density of B-DNA in 1-1 valent and 2-2 valent salt
      solutions. We find that under all conditions considered here the free energy of
      the CC1 and the CC2 models is higher than that of the PB model. We argue that
      counterion condensation theory imposes nonphysical constraints and is, therefore,
      a poorer approximation to the underlying physics based on continuum dielectrics,
      point-charge small ions, Poisson electrostatics, and Boltzmann distributions. The
      errors in counterion condensation theory diminish with increasing distance from,
      or radius of, the polyion.

PMID- 8527652
TI  - Single-particle tracking: effects of corrals.
AB  - Structural proteins of the membrane skeleton are thought to form "corrals" at the
      membrane surface, and these corrals may restrict lateral diffusion of membrane
      proteins. Recent experimental developments in single-particle tracking and laser
      trapping make it possible to examine the corral model in detail. Techniques to
      interpret these experiments are presented. First, escape times for a diffusing
      particle in a corral are obtained from Monte Carlo calculations and analytical
      solutions for various corral sizes, shapes, and escape probabilities, and reduced
      to a common curve. Second, the identification of corrals in tracking experiments
      is considered. The simplest way to identify corrals is by sight. If the walls are
      impermeable enough, a trajectory fills the corral before the diffusing particle
      escapes. The fraction of distinct sites visited before escape is calculated for
      corrals of various sizes, shapes, and escape probabilities, and reduced to a
      common curve. This fraction is also a measure of the probability that the
      diffusing species will react with another species in the corral before escaping.
      Finally, the effect of the sampling interval on the measurement of the short
      range diffusion coefficient is examined.

PMID- 8527653
TI  - 35Cl nuclear magnetic resonance line broadening shows that eosin-5-maleimide does
      not block the external anion access channel of band 3.
AB  - It has been suggested that Lys-430 of band 3, with which eosin-5-maleimide (EM)
      reacts, is located in the external channel through which anions gain access to
      the external transport site, and that EM inhibits anion exchange by blocking this
      channel. To test this, we have used 35Cl nuclear magnetic resonance (NMR) to
      measure Cl- binding to the external transport site in control and EM-treated
      human red blood cells. Intact cells were used rather than ghosts, because in this
      case all line broadening (LB) results from binding to external sites. In an NMR
      spectrometer with a 9.4-T magnetic field, red blood cells at 50% concentration
      (v/v) in 150 mM Cl- medium at 3 degrees C caused 19.0 +/- 1.2 Hz LB. Of this, 7.9
      +/- 0.7 Hz was due to Cl- binding to the high affinity band 3 transport sites,
      because it was prevented by an apparently competitive inhibitor of anion
      exchange, 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS). The LB was not due to
      hemoglobin released from the cells, as little LB remained in the supernatant
      after cells were removed by centrifugation. Saturable Cl- binding remained in EM
      treated cells, although the binding was no longer DNDS-sensitive, because EM
      prevents binding of DNDS. The lower limit for the rate at which Cl- goes from the
      binding site to the external medium is 2.15 x 10(5) s-1 for control cells and
      1.10 x 10(5) s-1 for EM-treated cells, far higher than the Cl- translocation rate
      at 3 degrees C (about 400 s-1). Thus, EM does not inhibit Cl- exchange by
      blocking the external access channel. EM may therefore be useful for fixing band
      3 in one conformation for studies of Cl- binding to the external transport site.

PMID- 8527654
TI  - Diacylglycerol analogs inhibit the rod cGMP-gated channel by a phosphorylation
      independent mechanism.
AB  - The electrical response to light in retinal rods is mediated by cyclic nucleotide
      gated, nonselective cation channels in the outer segment plasma membrane.
      Although cGMP appears to be the primary light-regulated second messenger,
      cellular levels of other substances, including Ca2+ and phosphatidylinositol-4,5
      bisphosphate, are also sensitive to the level of illumination. We now show that
      diacylglycerol (DAG) analogs reversibly suppress the cGMP-activated conductance
      in excised patches from frog rod outer segments. This suppression did not require
      nucleoside triphosphates, indicating that a phosphorylation reaction was not
      involved. DAG was more effective at low than at high [cGMP]: with 50 microM 8-Br
      cGMP, the DAG analog 1,2-dioctanoyl-sn-glycerol (1,2-DiC8) reduced the current
      with an IC50 of approximately 22 microM (Hill coefficient, 0.8), whereas with 1.2
      microM 8-Br-cGMP, only approximately 1 microM 1,2-DiC8 was required to halve the
      current. DAG reduced the apparent affinity of the channels for cGMP: 4 microM 1,2
      DiC8 produced a threefold increase in the K1/2 for channel activation by 8-Br
      cGMP, as well as a threefold reduction in the maximum current, without changing
      the apparent stoichiometry or cooperativity of cGMP binding. Inhibition by 1,2
      DiC8 was not relieved by supersaturating concentrations of 8-Br-cGMP, suggesting
      that DAG did not act by competitive inhibition of cGMP binding. Furthermore, DAG
      did not seem to significantly reduce single-channel conductance. A DAG analog
      similar to 1,2-DiC8--1,3-dioctanoyl-sn-glycerol (1,3-DiC8)--suppressed the
      current with the same potency as 1,2-DiC8, whereas an ethylene glycol of
      identical chain length (DiC8-EG) was much less effective. Our results suggest
      that DAG allosterically interferes with channel opening, and raise the question
      of whether DAG is involved in visual transduction.

PMID- 8527655
TI  - Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine
      enantiomers.
AB  - Stereoselective drug-channel interactions may help to elucidate the molecular
      basis of voltage-gated potassium channel block by local anesthetic drugs. We
      studied the effects of the enantiomers of bupivacaine on a cloned human cardiac
      potassium channel (hKv1.5). This channel was stably expressed in a mouse Ltk-
      cell line and studied using the whole-cell configuration of the patch-clamp
      technique. Both enantiomers modified the time course of this delayed rectifier
      current. Exposure to 20 microM of either S(-)-bupivacaine or R(+)-bupivacaine did
      not modify the activation time constant of the current, but reduced the peak
      outward current and induced a subsequent exponential decline of current with time
      constants of 18.7 +/- 1.1 and 10.0 +/- 0.9 ms, respectively. Steady-state levels
      of block (assessed with 250-ms depolarizing pulses to +60 mV) averaged 30.8 +/-
      2.5% (n = 6) and 79.5 +/- 3.2% (n = 6) (p < 0.001), for S(-)- and R(+)
      bupivacaine, respectively. The concentration dependence of hKv1.5 inhibition
      revealed apparent KD values of 27.3 +/- 2.8 and 4.1 +/- 0.7 microM for S(-)
      bupivacaine and R(+)-bupivacaine, respectively, with Hill coefficients close to
      unity, suggesting that binding of one enantiomer molecule per channel was
      sufficient to block potassium permeation. Analysis of the rate constants of
      association (k) and dissociation (l) yielded similar values for l (24.9 s-1 vs.
      23.6 s-1 for S(-)- and R(+)-bupivacaine, respectively) but different association
      rate constants (1.0 x 10(6) vs. 4.7 x 10(6) M-1 s-1 for S(-)- and R(+)
      bupivacaine, respectively). Block induced by either enantiomer displayed a
      shallow voltage dependence in the voltage range positive to 0 mV, i.e., where the
      channel is fully open, consistent with an equivalent electrical distance delta of
      0.16 +/- 0.01. This suggested that at the binding site, both enantiomers of
      bupivacaine experienced 16% of the applied transmembrane electrical field,
      referenced to the inner surface. Both bupivacaine enantiomers reduced the tail
      current amplitude recorded on return to -40 mV and slowed their time course
      relative to control, resulting in a "crossover" phenomenon. These data indicate
      1) the charged form of both bupivacaine enantiomers block the hKv1.5 channel
      after it opens, 2) binding occurs within the transmembrane electrical field, 3)
      unbinding is required before the channel can close, 4) block of hKv1.5 channels
      by bupivacaine is markedly stereoselective, with the R(+)-enantiomer being the
      more potent one, 5) this stereoselective block was associated with a 1.11 
      kcal/mol difference in binding energy between both enantiomers, and 6) the
      stereoselectivity derives mainly from a difference in the association rate
      constants, suggesting that the S(-)-enantiomer is less likely to access the
      binding site in an optimal configuration.

PMID- 8527656
TI  - Multiple residues specify external tetraethylammonium blockade in voltage-gated
      potassium channels.
AB  - We have mapped residues in the carboxyl half of the P region of a voltage-gated
      K+ channel that influence external tetraethylammonium (TEA) block. Fifteen amino
      acids were substituted with cysteine and expressed in oocytes from monomeric or
      heterodimeric cRNAs. From a total of six mutant channels with altered TEA
      sensitivity, three were susceptible to modification by extracellularly applied
      charged methanethiosulfonates (MTSX). Another residue did not affect TEA block
      but was protected from MTSX by TEA. MTSX modification of position Y380C, thought
      to form the TEA binding site, affected TEA affinity only moderately, and this
      effect could be reversed by additional charge transfer from an oppositely charged
      MTSX analog. The results show that TEA block is modulated from multiple sites,
      including residues located deep in the pore and that several side chains besides
      that of Y380 are exposed at the TEA receptor.

PMID- 8527657
TI  - Species heterogeneity of Gly-11 gramicidin A incorporated into sodium dodecyl
      sulfate micelles.
AB  - Evidence is presented for species heterogeneity of the gly-11 analog of
      gramicidin A incorporated into sodium dodecyl sulfate (SDS) micelles. The
      evidence for species heterogeneity has been obtained using one-dimensional (1D)
      1H NMR spectroscopy. The 1D spectra of the indole NH moiety of tryptophans 9, 13,
      and 15 show the presence of more than one species. It has been found that the
      heterogeneity is dependent upon the gly-11/SDS molar ratio. At high SDS
      concentration (i.e., gly-11/SDS of 3 mM/700 mM) the heterogeneity almost
      completely disappears. The temperature dependence of these 1H NMR signals
      suggests that the two species do not interconvert. The results of nuclear
      Overhauser effect spectroscopy NMR experiments indicate that one species is
      embedded within the micelle, while the other is nearer the aqueous interface. The
      importance of side chain interactions with the membrane environment in producing
      stable, solubilized species of small peptides in SDS micelles is illustrated.

PMID- 8527658
TI  - Effect of blocking the Na+/K+ ATPase on Ca2+ extrusion and light adaptation in
      mammalian retinal rods.
AB  - Membrane current and light response were recorded from rods of monkey and guinea
      pig by means of suction electrodes. The correlation between adaptation and the
      Na+/K+ pump was investigated by measuring light-dependent changes in sensitivity
      with and without inhibition of Na+/K+ ATPase by strophanthidin. Strophanthidin
      was found to reduce the dark current, to slow the time course of the
      photoresponse, and to increase light sensitivity. At concentrations between 20
      and 500 nM, the pump inhibitor suppressed in a reversible way the current re
      activation occurring during prolonged illumination and modified the light
      dependent decrease in sensitivity, which in control conditions approximates to a
      Weber-Fechner function. The effects of the pump inhibitor on the adaptive
      properties of rods are associated with an increased time constant of the membrane
      current attributed to the operation of the Na+:Ca2+,K+ exchanger. The effects of
      rapid application of the pump inhibitor on the current re-activation are
      consistent with the idea that significant changes in the internal sodium occur in
      rods of mammals during background illumination and that they play an important
      role in the process of light adaptation.

PMID- 8527659
TI  - Hydrophobic ions amplify the capacitive currents used to measure exocytotic
      fusion.
AB  - The detection of exocytotic fusion in patch-clamped secretory cells depends on
      measuring an increase in the cell membrane capacitance as new membrane is added
      to the plasma membrane. However, in the majority of secretory cells, secretory
      vesicles are too small (< 200 nm in diameter) to cause a detectable signal. We
      have found that incubations of normal mouse mast cells with the hydrophobic anion
      dipicrylamine (DPA), increases cell membrane capacitance by about three times.
      The large capacitive current induced by DPA was voltage-dependent, having a
      maximum value at -10 mV. The DPA-induced charge movement could be described by a
      single barrier model in which the DPA molecules move between two stable states in
      the bulk lipid matrix of the membrane. More importantly, the DPA treatment
      produced a sevenfold increase in the size of the capacitance steps observed upon
      the exocytotic fusion of single secretory granules. A similar amplification of
      DPA on the secretory vesicle capacitance was observed in a cell with larger (< or
      = 5 microns in diameter) or with smaller secretory granules (< 250 nm in
      diameter). Additionally, the increased granule membrane capacitance enlarged the
      transient capacitive discharge measured upon formation of a fusion pore in normal
      mast cell granules. Our results indicate that hydrophobic ions provide an
      important tool for high resolution studies of membrane capacitance.

PMID- 8527660
TI  - Effects of chain unsaturation on the equation of state for lipid monolayers at
      the air-water interface.
AB  - An equation of state for lipid monolayers at the air-water interface is
      presented, which takes into account the effects of the conformation and the
      number and position of double bonds of the hydrocarbon chains. The total
      Hamiltonian of the monolayer is assumed to consist of three terms. Two of them
      are calculated exactly within the limitations of the formulation. These are the
      two-dimensional entropy of mixing of the lipid and water molecules at the surface
      and the conformational entropy of the chains using a model available from the
      literature. These two terms give rise to positive surface pressure. The third
      term, which includes all energies that are not amenable to calculation, was
      obtained as the difference between the sum of the two calculated terms and
      experimental data and is found to represent an approximately area-independent
      tension. The effects of chain unsaturation on the equation of state were modeled
      in the present theory in two ways; the chain bend caused by cis double bonds
      increases the minimal molecular area, and the double bond linkage on a chain
      decreases the degrees of freedom of the chain. Calculations revealed that the
      former is highly significant whereas the latter is negligible. The deduced
      equation of state reproduces experimental data with appropriate values for three
      parameters, which represent the collapse area, the overlap of adjacent chains,
      and the combined effects of the intra- and intermolecular interactions other than
      the surface mixing entropy and the chain conformational energy.

PMID- 8527661
TI  - Site of action of the local anesthetic tetracaine in a phosphatidylcholine
      bilayer with incorporated cardiolipin.
AB  - Tetracaine (TTC) increases the permeability of phospholipid liposomal membranes
      to water, and this increase is reduced by the incorporation of cardiolipin into
      the membranes. We examined the molecular interaction of a phospholipid with the
      TTC cation in egg-yolk phosphatidylcholine (EyPC) liposomal membranes with
      incorporated bovine heart cardiolipin (BhCL) by IR spectroscopy and by
      determination of partitioning and the pKa of membrane-bound TTC. The IR spectra
      indicated that TTC shifted the stretching band of the BhCL PO2- group, a
      potential site of hydration in the bilayer, to a lower frequency but did not
      shift that of EyPC. TTC intercalated into the BhCL bilayer shifted its aromatic C
      N stretching band to a lower frequency. One molecule of TTC was found to bind
      approximately five molecules of EyPC, and the incorporation of negatively charged
      BhCL into EyPC membranes increased the degree of binding of TTC to the bilayer
      membranes. The pKa values of TTC bound to membranes were determined as 7.7, 9.4,
      and 10.2 for EyPC membranes, EyPC membranes containing 50 mol % BhCL, and BhCL
      membranes, respectively, whereas that in an aqueous 10-mM NaCl solution was 8.5,
      as it was dependent on the manner of binding. The IR data together with the
      partitioning and the pKa data suggested differences between the actions of the
      TTC cation on negatively charged BhCL and on neutrally charged EyPC polar groups
      in the region close to the aqueous interface of the lipid bilayer.

PMID- 8527662
TI  - Measurement of erythrocyte membrane elasticity by flicker eigenmode
      decomposition.
AB  - We have studied the flickering of erythrocytes at wavelengths comparable to the
      cell dimension. To do this we have analyzed the edge fluctuations of the cell to
      a resolution of 5 nm by combining phase contrast microscopy with fast image
      processing. By measuring the edge excitations simultaneously at four orthogonal
      positions around the cell, the eigenmodes of equal azimuthal mode numbers m =
      0,1,2 could be separated. From a continuous time sequence of 100 s of video
      frames taken at 40 ms time intervals, we determined the time-auto correlation
      function for the modes m = 0,1,2 and calculated their mean square amplitudes
      <delta n2m> as well as their decay times tau m. To explain the results we also
      present the theoretically calculated energy eigenmodes of an erythrocyte,
      accounting for the constraint that the cell is in contact with the substrate
      along an annular ring, which agreed well with the experimental findings. We found
      that the softest mode is a "hindered translational" mode with m = 1 of the
      adhered cell, which is almost insensitive to the shear elastic modulus.
      Comparison of the calculated and measured amplitudes yielded an average value for
      the bending stiffness of kc = 4 x 10(-19) J, which is much larger than the value
      obtained by flicker analysis at short wavelengths (kc = 2.3 x 10(-20) J). It
      would, however, agree well with the value expected from the red cell membrane
      area compressibility modulus of K = 4.5 x 10(-1)N/m, which corresponds to a lipid
      bilayer containing approximately 50 mol % of cholesterol. In contradiction to our
      theoretical expectations we found that the flicker eigenmodes seemed not to be
      influenced by the membrane shear elasticity, which will be discussed in terms of
      an unusual coupling between the lipid bilayer and the cytoskeleton.

PMID- 8527663
TI  - Lateral electrical conductivity of mica-supported lipid bilayer membranes
      measured by scanning tunneling microscopy.
AB  - Lateral electric conductivity of mica-supported lipid monolayers and of the
      corresponding lipid bilayers has been studied by means of scanning tunneling
      microscopy (STM). The surface of freshly cleaved mica itself was found to be
      conductive when exposed to humid air. Lipid monolayers were transferred onto such
      a surface by means of the Langmuir-Blodgett technique, which makes the mica
      surface hydrophobic and suppresses the electric current along the surface in the
      experimentally accessible humidity (5-80%) and applied voltage (0-10 V) range.
      This is true for dipalmitoylphosphatidylethanolamine (DPPE) as well as
      dipalmitoylphosphatidylcholine (DPPC) monolayers. Repeated deposition of DPPC
      layers by means of the Langmuir-Blodgett LB technique does not lead to the
      formation of a stable surface-supported bilayer because of the high
      hydrophilicity of the phosphatidylcholine headgroups that causes DPPC/DPPC
      bilayers to peel off the supporting surface during the sample preparation. In
      contrast to this, a DPPE or a DPPC monolayer on top of a DPPE monolayer gives
      rise to a rather stable mica-supported bilayer that can be studied by STM.
      Electric currents between 10 and 100 fA, depending on the ambient humidity, flow
      along the DPPE bilayer surface, in the humidity range between 35 and 60%. The
      DPPC surface, which is more hydrophilic, is up to 100 times more conductive under
      comparable conditions. Anomalous high lateral conductivity thus depends on, and
      probably proceeds via, the surface-adsorbed water layers. The prominence of
      ambient humidity and surface hydrophilicity on the measured lateral currents
      suggests this. The combination of our STM data and previously published water
      adsorption isotherms as a function of the relative humidity indicate that one
      layer or less of adsorbed water suffices for mediating the measurable lateral
      currents. The fact that similar observations are also made for other hydrophilic
      substrates supports the conclusion that lateral conductivity via surface-adsorbed
      water is a rather general phenomenon.

PMID- 8527664
TI  - Electron spin resonance studies of acyl chain motion in reconstituted nicotinic
      acetylcholine receptor membranes.
AB  - The electron spin resonance spectra of spin-label positional isomers of stearic
      acid (n-SASL) incorporated into nicotinic acetylcholine receptors (nAcChoR)
      reconstituted into dioleoylphosphatidylcholine (DOPC) were deconvoluted into
      bilayer- and protein-associated components by subtraction under conditions of
      slow exchange. The selectivity of n-SASL (n = 6, 9, 12, and 14) for the lipid
      protein interface of the nAcChoR was threefold greater than that of DOPC and
      independent of the spin label position. The temperature at which exchange became
      apparent as judged from lineshape broadening of the mobile lipid component
      spectrum was dependent upon the position of the spin-label moiety; near the
      bilayer center, exchange broadening occurred at lower temperatures than it did
      closer to the lipid headgroup. This suggests that the lipid headgroup region of
      boundary lipids is relatively fixed, whereas its acyl chain whips on and off the
      protein with increasing frequency near the bilayer center. Motions on the
      microsecond time scale were examined by microwave power saturation. Each n-SASL
      saturated more readily when incorporated into vesicles containing the nAcChoR
      than when in pure DOPC liposomes. Therefore, lipid mobility is perturbed by the
      nAcChoR on the microsecond time scale with an apparent magnitude that is
      relatively modest, probably due to exchange on this time scale.

PMID- 8527665
TI  - Fluorescence of membrane-bound tryptophan octyl ester: a model for studying
      intrinsic fluorescence of protein-membrane interactions.
AB  - The fluorescence of a membrane-bound tryptophan derivative (tryptophan octyl
      ester, TOE) has been examined as a model for tryptophan fluorescence from
      proteins in membrane environments. The depth-dependent fluorescence quenching of
      TOE by brominated lipids was found to proceed via a dynamic mechanism with
      vertical fluctuations playing a central role in the process. The activation
      energy for the quenching was estimated to be 1.3 kcal/mole. The data were
      analyzed using the distribution analysis (DA) method, which extends the
      conventional parallax method to account more realistically for the transbilayer
      distributions of both probe and quencher and for possible variations in the
      probe's accessibility. DA provides a better fit than the parallax method to data
      collected with TOE in membranes formed of lipids brominated at either the 4,5,
      the 6,7, the 9,10, or the 11,12 positions of the sn-2 acyl chain. DA yields
      information on the fluorophore's most probable depth in the membrane, its
      conformational heterogeneity, and its accessibility to the lipid phase.
      Previously reported data on cytochrome b5 and melittin were reanalyzed together
      with data obtained with TOE. This new analysis demonstrates conformational
      heterogeneity in melittin and provides estimates of the freedom of motion and
      exposure to the lipid phase of membrane-embedded tryptophans of cytochrome b5.

PMID- 8527666
TI  - Hydrostatic pressure-induced conformational changes in phosphatidylcholine
      headgroups: a 2H NMR study.
AB  - The effects of pressure and temperature on 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine headgroup
      conformations were examined using deuterium nuclear magnetic resonance.
      Isothermal compression was found to produce a decrease in the choline alpha
      deuteron quadrupole splitting and increases in the choline beta and gamma
      deuteron quadrupole splittings. A similar counterdirectional change, seen in the
      presence of positive surface charge, has been attributed to tilting of the
      headgroup away from the bilayer surface in response to the torque exerted on the
      phosphocholine dipole by positive surface charges. The direction of the change in
      headgroup deuteron quadrupole splitting is consistent with the pressure-induced
      reduction in area per lipid in the liquid crystalline phase, which can be
      inferred from the ordering of phospholipid acyl chains under comparable
      conditions. The temperature dependences of the headgroup deuteron quadrupole
      splittings were also examined. It was found that at elevated pressure, the alpha
      splitting was insensitive to temperature, whereas the beta and gamma splittings
      decreased. The response of the beta deuteron splitting to temperature was found
      to be weaker at elevated pressure than at ambient pressure.

PMID- 8527667
TI  - Strain-dependent cross-bridge cycle for muscle.
AB  - The cross-bridge cycle for actin, S1 myosin, and nucleotides in solution is
      applied to the sliding filament model for fully activated striated muscle. The
      cycle has attached and rotated isomers of each actomyosin state. It is assumed
      that these forms have different zero-strain conformations with respect to the
      filament and that strain-free rate constants are the nominal solution values.
      Only one S1 unit of heavy meromyosin is considered. Transition-state theory is
      used to predict the strain dependences of S1 binding to actin, the force
      generating transition to rotated states, and the release/binding of nucleotide
      and phosphate. We propose that ADP release and ATP binding are blocked by
      positive strain and phosphate release by negative strain. At large strains, rapid
      dissociation of S1 nucleotide from actin is expected when the compliant element
      of the cross-bridge is strained in either direction beyond its elastic limits.
      The dynamical behavior of this model of muscle contraction is discussed in
      general terms. Its computed steady-state properties are presented in an
      accompanying paper.

PMID- 8527668
TI  - Strain-dependent cross-bridge cycle for muscle. II. Steady-state behavior.
AB  - Quantitative predictions of steady-state muscle properties from the strain
      dependent cross-bridge for muscle are presented. With a stiffness of 5.4 x 10(-4)
      N/m per head, a throw distance of 11 nm, and three allowed actin sites/head,
      isometric properties and their dependence on phosphate and nucleotide levels are
      well described if the tension-generating step occurs before phosphate release. At
      very low ATP levels, rigorlike states with negative strain are predicted. The
      rate-limiting step for cycling and ATP consumption is strain-blocked ADP release
      for isometric and slowly shortening muscle. Under rapid shortening, ATP
      hydrolysis on detached heads is the rate-limiting step, and the ratio of bound
      ATP to bound ADP.Pi increases by a factor of 7. At large positive strains, bound
      heads must be forcibly detached from actin to account for tension in rapid
      extension, but forced detachment in shortening has no effect without destroying
      isometric attached states. Strain-blocked phosphate release as proposed produces
      modest inhibition of the ATPase rate under rapid shortening, sufficient to give a
      maximum for one actin site per helix turn. Alternative cross-bridge models are
      discussed in the light of these predictions.

PMID- 8527669
TI  - Crystal structure of the A-DNA decamer d(CCIGGCCm5CGG) at 1.6 A showing the
      unexpected wobble I.m5C base pair.
AB  - The crystal structure of the self-complementary decamer d(CCIGGCCm5CGG), where I
      and m5C replace A and T, respectively, in the Watson-Crick B-DNA decamer
      d(CCAGGCCTGG) is in the A-DNA conformation. Furthermore, the A-DNA duplex
      exhibits the unexpected wobble I.m5C+ base pairs with N3 of 5-methylcytosine
      protonated. The crystals belong to the orthorhombic system, space group
      P2(1)2(1)2(1), with a = 25.02, b = 44.95 and c = 47.62 A with one DNA duplex in
      the asymmetric unit. Intensity data were collected on our Siemens area detector
      to 1.6 A resolution. The structure was solved by the molecular placement method
      starting with a model from an isomorphous structure. The refinement gave a final
      R value of 16.3% for 404 DNA atoms and 104 water molecules using 5119
      reflections. The hydration of the I.m5C+ wobble base pairs in the major groove
      stabilizes them as in the G.T/G.U wobbles. A comparison with the Watson-Crick
      base pairs of another isomorphous structure d(GCGGGCCCGC) reveals that the wobble
      base pairs are better described by a rotation of the individual nucleotide units
      around their centers of gravity. This is in contrast to the earlier description
      of translation of the bases into the grooves. The exposed N4 amino group of 5
      methylcytosine in the wobble base pair provides a rationale for its deamination
      to thymine.

PMID- 8527670
TI  - Influence of counter-ions on the crystal structures of DNA decamers: binding of
      [Co(NH3)6]3+ and Ba2+ to A-DNA.
AB  - A-DNA is a stable alternative right-handed double helix that is favored by
      certain sequences (e.g., (dG)n.(dC)n) or under low humidity conditions. Earlier A
      DNA structures of several DNA oligonucleotides and RNA.DNA chimeras have revealed
      some conformational variation that may be the result of sequence-dependent
      effects or crystal packing forces. In this study, four crystal structures of
      three decamer oligonucleotides, d(ACCGGCCGGT), d(ACCCGCGGGT), and
      r(GC)d(GTATACGC) in two crystal forms (either the P6(1)22 or the P2(1)2(1)2(1)
      space group) have been analyzed at high resolution to provide the molecular basis
      of the structural difference in an experimentally consistent manner. The study
      reveals that molecules crystallized in the same space group have a more similar A
      DNA conformation, whereas the same molecule crystallized in different space
      groups has different (local) conformations. This suggests that even though the
      local structure is influenced by the crystal packing environments, the DNA
      molecule adjusts to adopt an overall conformation close to canonical A-DNA. For
      example, the six independent CpG steps in these four structures have different
      base-base stacking patterns, with their helical twist angles (omega) ranging from
      28 degrees to 37 degrees. Our study further reveals the structural impact of
      different counter-ions on the A-DNA conformers. [Co(NH3)6]3+ has three unique A
      DNA binding modes. One binds at the major groove side of a GpG step at the O6/N7
      sites of guanine bases via hydrogen bonds. The other two modes involve the
      binding of ions to phosphates, either bridging across the narrow major groove or
      binding between two intra-strand adjacent phosphates. Those interactions may
      explain the recent spectroscopic and NMR observations that [Co(NH3)6]3+ is
      effective in inducing the B- to A-DNA transition for DNA with (G)n sequence.
      Interestingly, Ba2+ binds to the same O6/N7 sites on guanine by direct
      coordinations.

PMID- 8527671
TI  - Probing local secondary structure by fluorescence: time-resolved and circular
      dichroism studies of highly purified neurotoxins.
AB  - The relationship between beta-sheet secondary structure and intrinsic tryptophan
      fluorescence parameters of erabutoxin b, alpha-cobratoxin, and alpha-bungarotoxin
      were examined. Nuclear magnetic resonance and x-ray crystallography have shown
      that these neurotoxins have comparable beta-sheet, beta-turn, and random coil
      secondary structures. Each toxin contains a single tryptophan (Trp) residue
      within its beta-sheet. The time-resolved fluorescence properties of native
      erabutoxin b and alpha-cobratoxin are best described by triple exponential decay
      kinetics, whereas native alpha-bungarotoxin exhibits more than four lifetimes.
      The disulphide bonds of each toxin were reduced to facilitate carboxymethylation
      and amidocarboxymethylation. The two different toxin derivatives of all three
      neurotoxins displayed triple exponential decay kinetics and were completely
      denatured as evidenced by circular dichroism (random coil). The concentration (c)
      values of the three fluorescence decay times (time-resolved fluorescence
      spectroscopy (TRFS)) were dramatically different from those of the native toxins.
      Each neurotoxin, treated with different concentrations of guanidinium
      hydrochloride (GuHCl), was studied both by circular dichroism and TRFS.
      Disappearance of the beta-sheet secondary structural features with increasing
      concentrations of GuHCl was accompanied by a shift in the relative contribution
      (c value) of each fluorescence decay time (TRFS). It was found that certain
      disulphide residues confer added stability to the beta-sheet secondary structure
      of these neurotoxins and that the center of the beta-sheet is last to unfold.
      These titrations show that Trp can be used as a very localized probe of secondary
      structure.

PMID- 8527672
TI  - Energy landscape of the tautomer states of mesoporphyrin embedded in horseradish
      peroxidase.
AB  - The energy hypersurface of the dominant tautomer states of mesoporphyrin
      substituted horseradish peroxidase was determined by creation of a nonequilibrium
      population of these states through photochemical transformation at 5 K and
      measurement of the temperature changes of the respective spectral bands as they
      were warmed to room temperature.

PMID- 8527673
TI  - Role of globin moiety in the autoxidation reaction of oxymyoglobin: effect of 8 M
      urea.
AB  - It is in the ferrous form that myoglobin or hemoglobin can bind molecular oxygen
      reversibly and carry out its function. To understand the possible role of the
      globin moiety in stabilizing the FeO2 bond in these proteins, we examined the
      autoxidation rate of bovine heart oxymyoglobin (MbO2) to its ferric met-form
      (metMb) in the presence of 8 M urea at 25 degrees C and found that the rate was
      markedly enhanced above the normal autoxidation in buffer alone over the whole
      range of pH 5-13. Taking into account the concomitant process of unfolding of the
      protein in 8 M urea, we then formulated a kinetic procedure to estimate the
      autoxidation rate of the unfolded form of MbO2 that might appear transiently in
      the possible pathway of denaturation. As a result, the fully denatured MbO2 was
      disclosed to be extremely susceptible to autoxidation with an almost constant
      rate over a wide range of pH 5-11. At pH 8.5, for instance, its rate was nearly
      1000 times higher than the corresponding value of native MbO2. These findings
      lead us to conclude that the unfolding of the globin moiety allows much easier
      attack of the solvent water molecule or hydroxyl ion on the FeO2 center and
      causes a very rapid formation of the ferric met-species by the nucleophilic
      displacement mechanism. In the molecular evolution from simple ferrous complexes
      to myoglobin and hemoglobin molecules, therefore, the protein matrix can be
      depicted as a breakwater of the FeO2 bonding against protic, aqueous solvents.

PMID- 8527674
TI  - Classes of hydration sites at protein-water interfaces: the source of contrast in
      magnetic resonance imaging.
AB  - Immobilized protein solute, approximately 20 wt %, alters the longitudinal and
      transverse nuclear magnetic relaxation rates 1/T1 and 1/T2 of solvent water
      protons in a manner that makes their values indistinguishable from those of a
      typical human tissue. There is now a quantitative theory at the molecular level
      (S.H. Koenig and R. D. Brown III (1993) Magn. Reson. Med. 30:685-695) that
      accounts for this, as a function of magnetic field strength, in terms of several
      distinguishable classes of water-binding sites at the protein-water interface at
      which significant relaxation and solute-solvent transfer of proton Zeeman energy
      occur. We review the arguments that these several classes of sites, characterized
      by widely disparate values of the resident lifetimes tau M of the bound waters,
      are associated with different numbers of hydrogen bonds that stabilize the
      particular protein-water complex. The sites that dominate relaxation-and produce
      contrast in magnetic resonance imaging (MRI), which derives from 1/T1 and 1/T2 of
      tissue water protons-have tau M approximately 10(-6)s. These, which involve four
      hydrogen bonds, occupy < or = 1% of the protein-water interface. Sites that
      involve three bonds, although more numerous, have < or = 20% smaller intrinsic
      effect on relaxation. The greater part of the "traditional" hydration monolayer,
      with even shorter-lived hydrogen-bonded waters, has little influence on solvent
      relaxation and is relatively unimportant in MRI. Finally, we argue, from the
      data, that most of the protein of tissue (a typical tissue is mostly protein)
      must be rotationally immobile (with Brownian rotational relaxation times slower
      than that of a 5 x 10(7) Da (very heavy) globular protein). We propose a
      functional basis for this immobilization ("cytoplasmic order"), and then indicate
      a way in which this order can break down ("cytoplasmic chaos") as a result of
      neoplastic transformation (cancer) and alter water-proton rates of pathological
      tissue and, hence, image contrast in MRI.

PMID- 8527675
TI  - Peptide binding domains determined through chemical modification of the side
      chain functional groups.
AB  - A clear understanding of the specific secondary structure and binding domain
      resulting from the interactions of proteins and peptides with lipid surfaces will
      provide insight into the specific functions of biologically active molecules. We
      have shown in earlier studies that the stationary phases used in reverse-phase
      high-performance liquid chromatography represent a model artificial lipid surface
      for the study of induced conformational states of peptides on lipid interaction.
      We have now used reverse-phase high-performance liquid chromatography to
      determine the binding domains of peptides and, by extension, of proteins to a
      lipid surface. This approach consists of performing chemical modifications of
      specific amino acid side-chain functionalities after the interaction of the
      peptides with the reverse-phase high-performance liquid chromatography C18
      groups. The susceptibility to oxidation was also studied after binding of the
      same peptides to liposomes. Oxidation of a single methionine residue "walked"
      through an amphipathic alpha-helical 18-mer peptide was selected to illustrate
      this approach. The extent of oxidation was found to be clearly dictated by the
      accessibility of the methionine residue to the aqueous mobile phase. The binding
      domain found for the peptide in its lipid-induced conformational state was
      unequivocally the entire hydrophobic face of the amphipathic alpha-helix.

PMID- 8527676
TI  - Pentagon packing models for "all-pentamer" virus structures.
AB  - A connection is made between 1) the observed structures of virus capsids whose
      capsomers are all pentamers and 2) the mathematical problem of determination of
      the largest size of a given number of equal regular spherical pentagons that can
      be packed on the surface of the unit sphere without overlapping. It is found that
      papillomaviruses provide the conjectured solution to the spherical pentagon
      packing problem for 72 pentagons. Thus, a study of some virus structures has
      given additional insight into a mathematical problem. At the same time this
      mathematical problem enables prediction of an octahedral form of papillomavirus
      particles consisting of 24 pentamers. It is also found that the various tubular
      and spherical "all-pentamer" virus structures identified so far can be
      represented by closet-packing arrangements of equal morphological units composed
      of equal regular pentagons on a cylinder and on a sphere.

PMID- 8527677
TI  - Determination of three-dimensional low-resolution viral structure from solution x
      ray scattering data.
AB  - The capsid is modeled as a region of constant electron density located between
      inner and outer envelopes that exhibit icosahedral symmetry. For computational
      purposes the envelopes are represented as truncated sums of weighted icosahedral
      harmonics. Methods are described for estimating the weights from x-ray solution
      scattering patterns based on nonlinear least squares, and two examples of the
      procedure, for viruses with known atomic-resolution structures, are given.

PMID- 8527678
TI  - Solvent effects on self-assembly of beta-amyloid peptide.
AB  - beta-amyloid peptide (A beta) is the primary protein component of senile plaques
      in Alzheimer's disease patients. Synthetic A beta spontaneously assembles into
      amyloid fibrils and is neurotoxic to cortical cultures. Neurotoxicity has been
      associated with the degree of peptide aggregation, yet the mechanism of assembly
      of A beta into amyloid fibrils is poorly understood. In this work, A beta was
      dissolved in several different solvents commonly used in neurotoxicity assays. In
      pure dimethylsulfoxide (DMSO), A beta had no detectable beta-sheet content; in
      0.1% trifluoroacetate, the peptide contained one-third beta-sheet; and in 35%
      acetonitrile/0.1% trifluoroacetate, A beta was two-thirds beta-sheet, equivalent
      to the fibrillar peptide in physiological buffer. Stock solutions of peptide were
      diluted into phosphate-buffered saline, and fibril growth was followed by static
      and dynamic light scattering. The growth rate was substantially faster when the
      peptide was predissolved in 35% acetonitrile/0.1% trifluoroacetate than in 0.1%
      trifluoroacetate, 10% DMSO, or 100% DMSO. Differences in growth rate were
      attributed to changes in the secondary structure of the peptide in the stock
      solvent. These results suggest that formation of an intermediate with a high beta
      sheet content is a controlling step in A beta self-assembly.

PMID- 8527679
TI  - Chemical platinization and its effect on excitation transfer dynamics and P700
      photooxidation kinetics in isolated photosystem I.
AB  - Isolated photosystem I (PSI) reaction center/core antenna complexes (PSI-40) were
      platinized by reduction of [PtCl6]2- at 20 degrees C and neutral pH. PSI
      particles were visualized directly on a gold surface by scanning tunneling
      microscopy (STM) before and after platinization. STM results showed that PSI
      particles were monomeric and roughly ellipsoidal with major and minor axes of 6
      and 5 nm, respectively. Platinization deposited approximately 1000 platinum atoms
      on each PSI particle and made the average size significantly larger (9 x 7 nm).
      In addition to direct STM visualization, the presence of metallic platinum on the
      PSI complexes was detected by its effect of actinic shading and electrostatic
      shielding on P700 photooxidation and P700+ reduction. The reaction centers (P700)
      in both platinized and nonplatinized PSI-40 were photooxidized by light and
      reduced by ascorbate repeatedly, although at somewhat slower rates in platinized
      PSI because of the presence of platinum. The effect of platinization on
      excitation transfer and trapping dynamics was examined by measuring picosecond
      fluorescence decay kinetics in PSI-40. The fluorescence decay kinetics in both
      platinized and control samples can be described as a sum of three exponential
      components. The dominant (amplitude 0.98) and photochemically limited excitation
      lifetime remained the same (16 ps) before and after platinization. The excitation
      transfer and trapping in platinized PSI-40 was essentially as efficient as that
      in the control (without platinization) PSI. The platinization also did not affect
      the intermediate-lifetime (400-600 ps) and long-lifetime (> 2500 ps) components,
      which likely are related to intrinsic electron transport and to functionally
      uncoupled chlorophylls, respectively. The amplitudes of these two components were
      exceptionally small in both of the samples. These results provide direct evidence
      that although platinization dramatically alters the photocatalytic properties of
      PSI, it does not alter the intrinsic excitation dynamics and initial electron
      transfer reactions in PSI.

PMID- 8527680
TI  - Vibrational neutron spectroscopy of collagen and model polypeptides.
AB  - A pulsed source neutron spectrometer has been used to measure vibrational spectra
      (20-4000 cm-1) of dry and hydrated type I collagen fibers, and of two model
      polypeptides, polyproline II and (prolyl-prolyl-glycine)10, at temperatures of 30
      and 120 K. the collagen spectra provide the first high resolution neutron views
      of the proton-dominated modes of a protein over a wide energy range from the low
      frequency phonon region to the rich spectrum of localized high frequency modes.
      Several bands show a level of fine structure approaching that of optical data.
      The principal features of the spectra are assigned. A difference spectrum is
      obtained for protein associated water, which displays an acoustic peak similar to
      pure ice and a librational band shifted to lower frequency by the influence of
      the protein. Hydrogen-weighted densities of states are extracted for collagen and
      the model polypeptides, and compared with published calculations. Proton mean
      square displacements are calculated from Debye-Waller factors measured in
      parallel quasi-elastic neutron-scattering experiments. Combined with the collagen
      density of states function, these yield an effective mass of 14.5 a.m.u. for the
      low frequency harmonic oscillators, indicating that the extended atom
      approximation, which simplifies analyses of low frequency protein dynamics, is
      appropriate.

PMID- 8527681
TI  - A ligand field model for MCD spectra of biological cupric complexes.
AB  - A ligand field calculation of magnetic circular dichroism (MCD) spectra is
      described that provides new insights into the information contained in electronic
      spectra of copper sites in metalloenzymes and synthetic analogs. The ligand field
      model uses metal-centered p- and f-orbitals to model sigma, pi LMCT mixing
      mechanism for intensity, allowing the basic features of optical absorption, MCD,
      and electron paramagnetic resonance spectra to be simultaneously computed from a
      single set of parameters and the crystallographically determined ligand
      coordinates. We have used the model to predict changes in spectra resulting from
      the transformation of electronic wavefunctions under systematic variation in
      geometry in pentacoordinate ML5 complexes. The effectiveness of the calculation
      is demonstrated for two synthetic copper model compounds and a galactose oxidase
      enzyme complex representing limiting coordination geometries. This analysis
      permits immediate recognition of characteristic patterns of MCD intensity and
      correlation with geometry. A complementarity principle between MCD and CD spectra
      of transition metal complexes is discussed.

PMID- 8527682
TI  - Subnanosecond polarized fluorescence photobleaching: rotational diffusion of
      acetylcholine receptors on developing muscle cells.
AB  - Polarized fluorescence recovery after photobleaching (PFRAP) is a technique for
      measuring the rate of rotational motion of biomolecules on living,
      nondeoxygenated cells with characteristic times previously ranging from
      milliseconds to many seconds. Although very broad, that time range excludes the
      possibility of quantitatively observing freely rotating membrane protein monomers
      that typically should have a characteristic decay time of only several
      microseconds. This report describes an extension of the PFRAP technique to a much
      shorter time scale. With this new system, PFRAP experiments can be conducted with
      sample time as short as 0.4 microseconds and detection of possible characteristic
      times of less than 2 microseconds. The system is tested on rhodamine-alpha
      bungarotoxin-labeled acetylcholine receptors (AChRs) on myotubes grown in primary
      cultures of embryonic rat muscle, in both endogenously clustered and nonclustered
      regions of AChR distribution. It is found that approximately 40% of the AChRs in
      nonclustered regions undergoes rotational diffusion fast enough to possibly arise
      from unrestricted monomer Brownian motion. The AChRs in clusters, on the other
      hand, are almost immobile. The effects of rat embryonic brain extract (which
      contains AChR aggregating factors) on the myotube AChR were also examined by the
      fast PFRAP system. Brain extract is known to abolish the presence of endogenous
      clusters and to induce the formation of new clusters. It is found here that
      rotational diffusion of AChR in the extract-induced clusters is as slow as that
      in endogenous clusters on untreated cells but that rotational diffusion in the
      nonclustered regions of extract-treated myotubes remains rapid.

PMID- 8527683
TI  - Modified spectrophotometer for multi-dimensional circular dichroism/fluorescence
      data acquisition in titration experiments: application to the pH and guanidine
      HCI induced unfolding of apomyoglobin.
AB  - In a previous paper (Ramsay and Eftink, Biophys. J. 66:516-523) we reported the
      development of a modified spectrophotometer that can make nearly simultaneous
      circular dichroism (CD) and fluorescence measurements. This arrangement allows
      multiple data sets to be collected during a single experiment, resulting in a
      saving of time and material, and improved correlation between the different types
      of measurements. The usefulness of the instrument was shown by thermal melting
      experiments on several different protein systems. This CD/fluorometer
      spectrophotometer has been further modified by interfacing with a syringe pump
      and a pH meter. This arrangement allows ligand, pH, and chemical denaturation
      titration experiments to be performed while monitoring changes in the sample's
      CD, absorbance, fluorescence, and light scattering properties. Our data
      acquisition program also has an ability to check whether the signals have
      approached equilibrium before the data is recorded. For performing pH titrations
      we have developed a procedure which uses the signal from a pH meter in a feedback
      circuit in order to collect data at evenly spaced pH intervals. We demonstrate
      the use of this instrument with studies of the unfolding of sperm whale
      apomyoglobin, as induced by acid pH and by the addition of guanidine-HCI.

PMID- 8527684
TI  - Atomic force microscope measurements and manipulation of Langmuir-Blodgett films
      with modified tips.
AB  - A simple method for rendering atomic force microscope tips and cantilevers
      hydrophilic or hydrophobic through glow discharge in an appropriate gas
      atmosphere is introduced. Force curves at different humidities of these modified
      cantilevers were taken on freshly cleaved mica (hydrophilic surface) and on a
      monolayer of dipalmitoylphosphatidylethanolamine transferred onto mica
      (hydrophobic surface) to characterize the behavior of the cantilevers on
      hydrophilic and hydrophobic surfaces. Furthermore, Langmuir-Blodgett bilayers,
      with a dipalmitoylphosphatidylethanolamine bottom layer and a
      dipalmitoylphosphatidylcholine top layer, were imaged in the constant force mode
      in a multimode atomic force microscope in air under controlled humidity
      conditions. The friction and elasticity signal were recorded parallel to the
      topography. By varying the force exerted by the tip on the sample, different
      layers of the Langmuir-Blodgett system could be removed or flattened. Removal
      exposed underlying layers that exhibited a different friction and elasticity
      behavior. Furthermore, force scans with tips rendered hydrophobic were taken on
      the different layers of the sample to characterize the hydrophilic/hydrophobic
      nature of the layers. Only by combining the results obtained by the different
      methods can the structure of the lipid layer systems be identified.

PMID- 8527685
TI  - Imaging of endosome fusion in BHK fibroblasts based on a novel fluorimetric
      avidin-biotin binding assay.
AB  - A fluorescence assay of in vivo endosome fusion was developed and applied to
      define the kinetics of endosome fusion in baby hamster kidney (BHK) fibroblasts.
      The assay is based on an approximately 10-fold enhancement of the green
      fluorescence of BODIPY-avidin upon biotin binding. The BODIPY-avidin fluorescence
      enhancement occurred in < 25 ms, was pH-independent, and involved a BODIPY
      tryptophan interaction. For endocytosis in vivo, BHK fibroblasts were pulse
      labeled with BODIPY-avidin together with a red (rhodamine) fluorescent fusion
      independent chromophore (TMR). After specified chase times in a nonfluorescent
      medium, a second cohort of endosomes was pulse-labeled with biotin-conjugated
      albumin, dextran, or transferrin. Fusion of biotin-containing endosomes with
      avidin-containing endosomes was quantified by ratio imaging of BODIPY-to-TMR
      fluorescence in individual endosomes, using imaging methods developed for
      endosome pH studies. Analysis of BODIPY-to-TMR ratio distributions in avidin
      labeled endosomes exposed to zero and maximum biotin indicated > 90% sensitivity
      for detection of endosome fusion. In avidin pulse (10 min) -chase-biotin albumin
      pulse (10 min) studies, both fused and unfused endosomes were identified; the
      fractions of avidin-labeled endosomes that fused with biotin-labeled endosomes
      were 0.48, 0.21, 0.16, and 0.07 for 0-, 5-, 10-, and 20-min chase times. Fitting
      of fusion data to a mathematical model of in vivo endosome fusion required the
      existence of an intermediate fusion compartment. Pulse-chase studies performed
      with biotin-transferrin to label the early/recycling endosomes indicated that
      after a 10-min chase, avidin-labeled endosomes reached a compartment that was
      inaccessible to biotin-transferrin. The assay was also applied to determine
      whether endosome fusion was influenced by temperature, pH (bafilomycin A1),
      second messengers (cAMP agonists, phorbol 12-myristate 13-acetate,
      staurosporine), and growth-related factors (platelet-derived growth factor,
      genistein). The results establish a sensitive fluorescence assay to quantify the
      fusion of vesicular compartments in living cells.

PMID- 8527686
TI  - Comparison of the gastrointestinal anatomy, physiology, and biochemistry of
      humans and commonly used laboratory animals.
AB  - In addition to metabolic differences, the anatomical, physiological, and
      biochemical differences in the gastrointestinal (G.I.) tract of the human and
      common laboratory animals can cause significant variation in drug absorption from
      the oral route. Among the physiological factors, pH, bile, pancreatic juice, and
      mucus and fluid volume and content can modify dissolution rates, solubility,
      transit times, and membrane transport of drug molecules. The microbial content of
      the G.I. tract can significantly affect the reductive metabolism and
      enterohepatic circulation of drugs and colonic delivery of formulations. The
      transit time of dosage forms can be significantly different between species due
      to different dimensions and propulsive activities of the G.I. tract. The
      lipid/protein composition of the enterocyte membrane along the G.I. tract can
      alter binding and passive, active, and carrier-mediated transport of drugs. The
      location and number of Peyer's patches can also be important in the absorption of
      large molecules and particulate matter. While small animals, rats, mice, guinea
      pigs, and rabbits, are most suitable for determining the mechanism of drug
      absorption and bioavailability values from powder or solution formulations,
      larger animals, dogs, pigs, and monkeys, are used to assess absorption from
      formulations. The understanding of physiological, anatomical, and biochemical
      differences between the G.I. tracts of different animal species can lead to the
      selection of the correct animal model to mimic the bioavailability of compounds
      in the human. This article reviews the anatomical, physiological, and biochemical
      differences between the G.I. tracts of humans and commonly used laboratory
      animals.

PMID- 8527687
TI  - Bioavailability of pseudoephedrine from controlled release formulations in the
      presence of guaifenesin in human volunteers.
AB  - A multiple-dose bioequivalence study with six healthy human volunteers was
      conducted. The bioavailability of an experimental controlled release tablet
      containing pseudoephedrine was compared with a marketed controlled release
      pseudoephedrine capsule in a three-way crossover study. Plasma samples, collected
      serially after oral drug administration, were analyzed for pseudoephedrine
      content using a specific HPLC method with UV detection. The bioavailability
      parameters, area under the concentration-time curve (AUC), maximum plasma
      concentration Cmax, and time to peak (Tmax) were obtained from the plasma
      concentration-time data. Additionally, model independent pharmacokinetic
      parameters were estimated. Analysis of variance of the data revealed no
      statistically significant differences between the test and the reference
      formulation. The presence of guaifenesin in the sustained release tablet did not
      influence pseudoephedrine bioavailability. The relative bioavailability of the
      tablet dosage form with respect to the capsule was found to be 100.8%. Classical
      and Westlake 95% confidence limits as well as the two one-sided t test, proposed
      by Schuirmann, and the Anderson-Hauck power analysis supported the inference that
      the two formulations demonstrated comparable bioavailabilty, even in the presence
      of guaifenesin. Using a non-linear regression program, it was found that the
      pharmacokinetics of pseudoephedrine followed a simple one-compartment disposition
      model with no lag time. Additionally, an in vitro-in vivo correlation, based on
      the estimation of cumulative relative fraction absorbed, was developed between
      the absorption of pseudoephedrine in humans and the in vitro dissolution time.

PMID- 8527688
TI  - Evaluation of the effects of ambroxol on the ofloxacin concentrations in
      bronchial tissues in COPD patients with infectious exacerbation.
AB  - Infectious excerbations of COPD are generally due to Streptococcus pneumoniae,
      Haemophilus species, and other Gram-negative bacteria. Ofloxacin has potent
      activity against Gram-negative species but is less effective against Gram
      positive species including Streptococcus pneumoniae. It has also been shown that
      the administration of ambroxol increases the concentration of some antibiotics in
      pulmonary tissues. The aim of the study was to determine whether ambroxol
      increases the bronchial tissue concentrations of ofloxacin to a level exceeding
      the MIC90 of the bacterial species less susceptible to ofloxacin. 24 patients
      with COPD were randomized in two groups. Drug regimens of ofloxacin alone (200 mg
      twice daily) or ofloxacin (200 mg twice daily)+ambroxol (30 mg thrice daily) were
      administered over 10 d. A fibroscopy was performed on day 10 with bronchial
      biopsies and broncho-alveolar lavage. At steady state, concentrations of drug in
      plasma and bronchial samples were assayed by HPLC with fluorometric detection.
      There was no significant difference in the bronchial levels of ofloxacin between
      the two groups; however, in alveolar cells, ofloxacin concentration was three
      times higher in the group with ambroxol. Ambroxol does not increase ofloxacin
      concentrations in bronchial tissue because high concentrations are already
      present in the lung.

PMID- 8527689
TI  - Disposition and bioavailability of the beta 1-adrenoceptor antagonist talinolol
      in man.
AB  - In an open randomized crossover study, the pharmacokinetics and bioavailability
      of the selective beta 1-adrenoceptor antagonist talinolol (Cordanum-
      Arzneimittelwerk Dresden GmbH, Germany) were investigated in twelve healthy
      volunteers (five female, seven male; three poor and nine extensive metabolizers
      of the debrisoquine hydroxylation phenotype) after intravenous infusion (30 mg)
      and oral administration (50 mg), respectively. Concentrations of talinolol and
      its metabolites were measured in serum and urine by HPLC or GC-MS. At the end of
      infusion a peak serum concentration (Cmax) of 631 +/- 95 ng mL-1 (mean +/- SD)
      was observed. The area under the serum concentration-time curve from zero to
      infinity (AUC0-infinity) was 1433 +/- 153 ng h mL-1. The following parameters
      were estimated: terminal elimination half life (t 1/2), 10.6 +/- 3.3 h; mean
      residence time, 11.6 +/- 3.1 h; volume of distribution, 3.3 +/- 0.5 L kg-1; and
      total body clearance, 4.9 +/- 0.6 mL min-1 kg-1. Within 36 h 52.8 +/- 10.6% of
      the administered dose was recovered as unchanged talinolol and 0.33 +/- 0.18% as
      hydroxylated talinolol metabolites in urine. After oral administration a Cmax of
      168 +/- 67 ng mL-1 was reached after 3.2 +/- 0.8 h. The AUC0-infinity was 1321 +/
      382 ng h mL-1. The t 1/2 was 11.9 +/- 2.4 h. 28.1 +/- 6.8% of the dose or 55.0
      +/- 11.0% of the bioavailable talinolol was eliminated as unchanged talinolol and
      0.26 +/- 0.17% of the dose as hydroxylated metabolites by kidney. The absolute
      bioavailability of talinolol was 55 +/- 15% (95% confidence interval, 36
      69%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527690
TI  - The acetylcholinesterase oxime reactivator HI-6 in man: pharmacokinetics and
      tolerability in combination with atropine.
AB  - In a double-blind, placebo-controlled, single-dose ascending pharmacokinetics and
      tolerance study, we evaluated the bispyridinium oxime HI-6 dichloride monohydrate
      (62.5, 125, 250, and 500 mg), administered intramuscularly with atropine
      sulphate, 2 mg, in 24 healthy male volunteers. The plasma HI-6 peak concentration
      (Cmax) and area under the concentration-time curve (AUC) demonstrated linear
      pharmacokinetics with low intradose variability, suggestive of uniformity of
      effect among subjects. HI-6 (500 mg) attained plasma drug concentrations that
      appeared adequate for practical use as an antidote. The mean +/- SD time to
      maximum plasma HI-6 concentration (tmax = 0.69 +/- 0.21 h, n = 16), and
      absorption half-life (t/2a = 0.17 +/- 0.05 h) indicated rapid onset of effect.
      The volume of distribution (Vd = 0.25 +/- 0.04 L kg-1 TBW) approximated the
      extracellular fluid volume. A high total body clearance (CL = 252 +/- 52 mL min
      1) and short apparent elimination half-life (t/2e = 1.15 +/- 0.19 h) were
      expected for this polar quaternary ammonium drug. The renal clearance CLr = 137
      +/- 33 mL min-1), which approximated the expected glomerular filtration rate, and
      24 h urinary excretion of unchanged drug (55 +/- 10%) indicated substantial non
      renal elimination. Blood pressure, heart rate, respiratory rate,
      electrocardiographic parameters, mental acuity, and vision were not altered.
      Adverse events and changes in serum, urine, and semen laboratory tests were mild.
      The pharmacokinetics, safety, and apparent efficacy of HI-6 suggest it may be a
      superior oxime antidote against nerve agent poisoning.

PMID- 8527691
TI  - Pharmacokinetics of the antiarrhythmic agent tiracizine: steady state kinetics in
      comparison with single-dose kinetics.
AB  - Serum and urine kinetics of unchanged tiracizine (T), a new class I
      antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight
      healthy extensive metabolizers after a single oral administration of 50 mg
      tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine
      induced ECG changes were measured. Considerable accumulation of M1 and M2 was
      observed during repeated dosing (M1, Cmax,ss = 391.8 ng mL-1 against Cmax,sd =
      132.8 ng mL-1; M2, Cmax,ss = 143.2 ng mL-1 against Cmax,sd = 25.8 ng mL-1).
      However, significant increases of AUC (AUC tau = 261.9 ng h mL-1 against AUC0
      infinity,sd = 182.9 ng h mL-1), Cmax (Cmax,ss = 75.9 ng mL-1 against Cmax,sd =
      56.9 ng mL-1) and t 1/2 beta (t 1/2 beta,ss = 4.0 h against t 1/2 beta,sd = 2.4
      h) of the parent compound indicate non-linear kinetics. The significant decrease
      in renal clearance of all four substances as well as the decrease of non-renal
      tiracizine clearance with repeated dosing led to the assumption that non
      linearity is due to saturable renal excretion and a fall in intrinsic tiracizine
      clearance. PQ time was prolonged significantly during steady state and culminated
      at the tmax of the parent compound, whereas there was no change in any ECG
      parameter after a single-dose administration of 50 mg tiracizine.

PMID- 8527692
TI  - Ageing, oscillations and efficiency.
AB  - The phenomenon of ageing still defies understanding. Theoretical studies have
      indicated that glycolysis is more efficient at maintaining a high ATP/ADP ratio
      when oscillating at its resonant frequency. Earlier, it was proposed that the
      differentiated state results from the establishment of a stable pattern of
      temporal organisation. It is now suggested that ageing involves a decrease in
      efficiency due to the detuning of oscillating glycolysis as a result of frequency
      locking with other cellular oscillations in the differentiated state.

PMID- 8527693
TI  - Multistaged corpuscular models of microbial growth: Monte Carlo simulations.
AB  - A new framework is developed by extending the existing population balance
      framework for modeling the growth of microbial populations. The new class of
      multistaged corpuscular models allows further structuring of the microbial life
      cycle into separate phases or stages and thus facilitates the incorporation of
      cell cycle phenomena to population models. These multistaged models consist of
      systems of population balance equations coupled by appropriate boundary
      conditions. The specific form of the equations depend on the assumed forms for
      the transition rate functions, the growth rate functions, and the partitioning
      function, which determines how the biological material is distributed at
      division. A growth model for ciliated protozoa is formulated to demonstrate the
      proposed framework. To obtain a solution to the system of the partial integro
      differential equations that results from such formulation, we adopted a Monte
      Carlo simulation technique which is very stable, versatile, and insensitive to
      the complexity of the model. The theory and implementation of the Monte Carlo
      simulation algorithm is analyzed and results from the simulation of the ciliate
      growth model are presented. The proposed approach seems to be promising for
      integrating single-cell mechanisms into population models.

PMID- 8527694
TI  - Ancient splice junction shadows with relation to blocks in protein structure.
AB  - Splice junction shadows (ancient exon-exon junctions) presumably reflect the
      existence of amino acid primary blocks which were used in the course of evolution
      for the construction of new proteins. The lengths of such blocks (i.e. regions
      between splice junctions), as the lengths of corresponding inserted or duplicated
      ancient exons, should be divisible by three in order to store the preexisting
      coding frame in the course of evolution. In this paper, we will test the
      hypothesis of intron-mediated recombination in a model of block molecular
      evolution (exon shuffling) by revealing corresponding blocks in existing database
      contained coding sequences. For this purpose, we use a weight matrix prediction
      of ancient splice junction shadows in coding regions of the nucleotide sequences
      in current databases. The usage of splice junction shadows allows us to test the
      block evolution hypothesis in better detail in comparison with previous methods
      which were based only on currently existing recent exons. Our result of block
      length distribution at the nucleotide level shows a clear tendency to be
      divisible by three. At the protein level, several unexpected favorable block
      lengths, which are six, nine, 12 and 15 amino acids in length, were observed.
      Further refinements in our method for revealing splice junction shadows
      (structural block boundaries) might reveal peptides which probably maintain
      stable folds in different structures. The latter can in turn be used for protein
      structure prediction.

PMID- 8527695
TI  - Differential length effects in a binary mixture of single chain amphiphiles in
      planar monolayers. A three-dimensional approach.
AB  - The purpose of this work was to investigate the selective association into a
      binary lipid mixture having the acyl chain lengths of the two components as
      variables. A more adequate parameter that can describe the selectivity of the
      association processes into a binary lipid mixture is the mean association
      probability. In the present paper, we used a three-dimensional approach by
      evaluating the mean probabilities of association of single chain amphiphile
      molecules for a group of 36 binary mixtures. The possible correlations between
      the hydrophobic chain lengths and the association processes have been carried out
      by using the differential mean association probabilities. These results allowed
      us to uncover some significant rules that govern the selective association
      between the two components from a single chain binary mixture. We have found that
      in a binary mixture of single chain amphiphiles, the distance where the
      dispersion forces become effective during association processes is about 8.89 A.

PMID- 8527696
TI  - Control of metabolic pathways by time-scale separation.
AB  - The bases underlying the distribution of metabolic control have been elusive,
      even though many intuitive arguments exist. To analyze this problem, we have
      applied the structural properties of the control coefficients to systems in which
      the eigenvalues of the Jacobian of the system are widely separated, that is,
      systems with time-scale separation. We show that time-scale separation is an
      effective way to localize metabolic control to only a few enzymes. To achieve
      time-scale separation, the cell can overproduce most of the enzymes relative to
      the required activity for the steady state, and control the expression level of
      only a few enzymes, provided that the overexpressed enzymes do not cause adverse
      effects. The overexpressed enzymes are responsible for the small response times
      of the system, and the reactions catalyzed by them are termed 'fast' reactions.
      The metabolite concentration control coefficients of the 'fast' reactions are
      always small compared with the 'slow' reactions. Furthermore, the 'fast'
      reactions do not have effective control on the overall flux. However, the 'fast'
      reactions may compete with each other at a branch point, leading to significant
      control coefficients for fluxes to the branches. These results are useful in
      justifying lumping of 'fast' reactions in mathematical modelling or in the
      experimental determination of control coefficients. The theoretical results are
      derived under the assumption that the system possesses a unique, asymptotically
      stable steady-state and that the reaction steps of the system under analysis are
      well represented by linear kinetics around the steady state. The application of
      the results presented in this article are demonstrated with three illustrative
      examples.

PMID- 8527697
TI  - Computational properties of self-reproducing growing automata.
AB  - Living organisms perform much better than computers at solving complex, irregular
      computational tasks, like search and adaptation. Key features of living
      organisms, identified in the paper as a basis for their success in solving
      complex problems, are: self-reproduction of cells, flexible framework, and
      modification. These key features of living organisms are abstracted into a
      computational model, called growing automata. Growing automata are suited for
      extremely large computational problems, such as search problems. Growing automata
      are representatives of soft machines. Soft machines can change their physical
      structure as opposed to hard machines which have fixed structure. An example of a
      soft machine is a living organism, an example of a hard machine is an electronic
      computer. The computational properties of soft and hard machines are analyzed and
      compared. An analysis of growing automata demonstrates their advantages, as well
      as their limitations as compared to hard machines.

PMID- 8527698
TI  - Adaptive determinism during salt-adaptation in Sorghum bicolr.
AB  - During adaptation to salinity, plants of Sorghum bicolor showed malformations
      affecting the leaves in development (DPL). At the end of the adaptation process,
      the plants were regrouped according to their pattern of DPL response. The
      distribution of the plant population in different patterns depended on
      environmental conditions. However, a positive relationship between the frequency
      of a pattern and its rate of development has been found. Similarly, a negative
      relation between the frequency of a pattern and the rate of senescence for the
      same pattern has been observed. The results reveal the existence of an
      orientation of the plant response towards the patterns with highest developmental
      rate and lowest rate of senescence. This property is defined as 'adaptive
      determinism'. Results indicate that the NaCl acts as a trigger for adaptation to
      a whole range of environmental perturbations. This suggests that adaptation to
      salinity is not a pre-programed response of the plants, and may be related to
      learning processes occurring in animals.

PMID- 8527699
TI  - Gastric microcirculatory disturbance and behaviour of leucocytes after thermal
      injury: intravital observation of arteriovenous shunting channels in the gastric
      submucosal layer.
AB  - In order to investigate the pathogenesis of acute gastric mucosal lesion after
      thermal injury, microcirculatory disturbance was assessed and observation of the
      behaviour of leucocytes was performed. Gastric blood flow decreased at 15 min
      post-thermal injury, and partially improved at 2 h; however, it decreased again
      at 5 h post-thermal injury. Mucosal microcirculatory disturbance was observed by
      using vascular labelling with monastral blue B. Deposits of monastral blue B were
      observed centring mainly on collecting venules but were also observed in the
      capillaries. Submucosal microcirculatory disturbance was observed through an
      intravital microscope. The irregularity of the wall and segmental constriction in
      the venules and presence of an arteriovenous shunting channel was observed in the
      submucosal layer at 5 h post-thermal injury. The percentage of rolling or
      sticking leucocytes that passed the confluence of a prevenule and a venule were
      significantly increased at 5 h after thermal injury. The present study revealed
      depression of gastric blood flow, mucosal and submucosal microcirculatory
      disturbance, and a significant increase of rolling and sticking leucocytes in the
      peripheral part of venules after thermal injury. Leucocyte-endothelial
      interactions may occur under such conditions and this interaction may play an
      important role in inducing the microcirculatory disturbance that results in an
      acute gastric mucosal lesion after thermal injury. The present study also
      demonstrated the possibility of intravital study of gastric submucosal
      arteriovenous shunting channels.

PMID- 8527700
TI  - Role of mucosal microcirculation in gastric lesions induced by lateral
      hypothalamic lesions in rats.
AB  - To evaluate the pathophysiology underlying gastric mucosal lesions induced by
      lateral hypothalamic (LH) lesions, we investigated the changes in acid secretion,
      gastric mucosal blood flow, gastric mucus and mucosal integrity in the corpus
      during the 4 h period and 48 h after the production of bilateral electrolytic LH
      lesions in male Sprague-Dawley rats. Gastric mucosal lesions were macroscopically
      produced 24 h (63%) and 48 h (83%) after LH lesions, although there were no
      visible lesions at 7 h. Gastric acid secretion was significantly increased 48 h
      after LH lesions, compared with that in the control group. Gastric mucosal blood
      flow and transmucosal potential difference (PD) in the LH lesion group
      immediately decreased after LH lesions and did not recover during 4 h and at 48
      h. On the contrary, in the control group, gastric mucosal blood flow decreased
      after the brain surgery but soon recovered, and there was no significant change
      in PD. LH lesions resulted in the reduction of intramucosal mucus to 50% 3 h
      after LH lesions. Moreover, we exposed the stomach to 10 mmol/L taurocholic acid
      (TCA) 3 h after LH lesions to examine the disruption in gastric mucosal defensive
      function in rats with LH lesions. The recovery of the reduced PD by TCA was slow
      and gastric mucosal lesions were easily formed in the LH lesion group. These
      results suggest that gastric mucosal ischaemia after lesioning of LH immediately
      results in the disruption of mucosal defensive function before the formation of
      visible gastric lesions, and predisposes to the formation of gastric mucosal
      lesions by a delayed increase in acid secretion.

PMID- 8527701
TI  - Roxatidine versus ranitidine in the treatment of duodenal ulcers: a randomized
      double-blind controlled multicentre study in Singapore.
AB  - Roxatidine acetate, a new H2 receptor antagonist, was compared with ranitidine in
      the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four
      patients with endoscopically proven duodenal ulcer were randomized to receive 150
      mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was
      performed after 4 weeks (25-33 days) and if the ulcer had not healed, another
      endoscopy was performed after a further 4 weeks of treatment. Using per protocol
      analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to
      72.2% of ulcers treated with ranitidine (P = NS). The healing rates at 8 weeks
      were 92% with roxatidine and 83.3% with ranitidine (P = NS). Using equivalence
      tests, the healing rate of roxatidine was found to be equivalent to that of
      ranitidine within a 20% region. Roxatidine users took significantly less antacids
      than ranitidine users (P < 0.05). There were no significant adverse effects due
      to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment
      of duodenal ulcers with a healing rate comparable to that of ranitidine.

PMID- 8527702
TI  - Intestinal absorption of lithocholate and its sulfate and glucuronide in rats.
AB  - The absorption of lithocholate and its sulfate and glucuronide in rat jejunum and
      terminal ileum was studied. Tracer amounts of radiolabelled bile acids were
      administered to the ligated intestinal segments, and their absorption was
      monitored by biliary excretion through a bile duct catheter. Absorption of
      lithocholate was faster in the terminal ileum than in the jejunum. Although the
      sulfation reduced lithocholate absorption in the jejunum, it did not affect
      lithocholate absorption in the terminal ileum. This was due to the Na+-dependency
      of ileal absorption of lithocholate-sulfate assessed by perfusion studies. In
      contrast, the glucuronidation markedly reduced lithocholate absorption both in
      the jejunum and the terminal ileum. These findings indicate that the
      glucuronidation is more effective than sulfation in detoxifying lithocholate as
      far as the prevention of its intestinal absorption is concerned.

PMID- 8527703
TI  - Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa.
AB  - Alterations in phenotype and function of intestinal macrophages occur in
      inflammatory bowel disease (IBD) but it is unclear whether these changes result
      from the recruitment of circulating monocytes to the intestine or from
      proliferation of resident intestinal macrophages. We sought to demonstrate the
      arrival of blood monocytes, the precursors of macrophages, in IBD mucosa.
      Peripheral blood mononuclear cells were isolated from 23 patients with clinically
      active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two
      infective colitis), then radiolabelled with 99mtechnetium (Tc)-stannous colloid
      (n = 13) or 111indium (In)-oxine (n = 10) before re-injection and abdominal
      scanning. Four patients had demonstrable intestinal monocyte uptake using [99mTc]
      stannous colloid, while six [111In]-oxine-labelled monocyte scans were positive.
      Uptake sites correlated with actively inflamed regions. Patients demonstrating
      monocyte uptake had been treated with corticosteroids for a significantly (P <
      0.02) shorter duration (median 3 vs 20 days) than those with negative scans.
      There was no significant difference between positive and negative scans for
      disease category, clinical or histological disease, activity, or radioisotope
      used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis
      who had positive scans showed a high proportion of CD14-positive macrophages, 4
      9% of which contained autoradiographic grains. These results demonstrate that
      blood monocytes are recruited to the mucosa of actively inflamed bowel, and
      suggest that this process may be inhibited by corticosteroids. Moreover, the
      phenotype of the recently-arrived monocytes indicates their susceptibility to
      stimulation by lipopolysaccharide, and suggests a mechanism for the continuing
      inflammation in the bacterial product-rich milieu of IBD.

PMID- 8527704
TI  - Immunolocalization of pS2, a putative growth factor, in pancreatic carcinoma.
AB  - pS2 is a 60 amino acid secretory polypeptide which belongs to a newly described
      family of trefoil-shaped growth factors. It is widely distributed throughout the
      gastrointestinal tract, particularly adjacent to damaged mucosa, and is also
      expressed by some epithelial tumours such as breast carcinoma. The aim of this
      study was to examine the expression of pS2 in pancreatic cancer. The presence of
      pS2 was analysed immunohistochemically using two antibodies, a polyclonal (pNR-2)
      and a monoclonal (pS2TM) in 42 cases of pancreatic adenocarcinoma and 10 cases of
      ampullary carcinoma. The findings were compared with chronic pancreatitis and
      normal pancreas. No immunostaining was seen in normal pancreas, with the
      exception of one area of ductular proliferation, and although 8/10 cases of
      chronic pancreatitis expressed pS2, it was focal and confined to the occasional
      duct. In contrast, a significant proportion of malignant cells in 23/42 (55%) of
      pancreatic adenocarcinoma and 8/10 (80%) of ampullary tumours expressed
      immunoreactive pS2. The finding of pS2 expression in more than 50% of pancreatic
      and ampullary carcinomas in contrast to the findings seen in chronic pancreatitis
      and normal pancreas suggests that pS2 may play an important role in the growth of
      these highly malignant tumours.

PMID- 8527705
TI  - Serum pepsinogen I and pepsinogen II, and the ratio of pepsinogen I/pepsinogen II
      in peptic ulcer diseases: with special emphasis on the influence of the location
      of the ulcer crater.
AB  - To investigate the effect of the location of the ulcer crater on the serum levels
      of pepsinogen I (PGI), pepsinogen II (PGII) and the ratio of PGI/PGII, these
      parameters were determined in 161 healthy controls, 29 patients with gastric
      ulcer in the gastric body (GU-I), 65 with coexistent gastroduodenal ulcer (GU
      II), 104 with gastric ulcer in the prepyloric region (GU-III), and 116 with
      duodenal ulcer (DU). Serum PGI levels were significantly higher (P < 0.01) in
      patients with GU-III (110.6 +/- 65.1 ng/mL), GU-II (100.0 +/- 46.6 ng/mL), and DU
      (92.2 +/- 35.2 ng/mL) than in the controls (77.4 +/- 31.4 ng/mL), while there
      were no significant differences between GU-I (82.5 +/- 36.3 ng/mL) and the
      controls. Patients with gastric ulcer in any region had significantly higher (P <
      0.01) serum PGII levels (GU-I, 20.0 +/- 15.7 ng/mL; GU-II, 15.5 +/- 10.9 ng/mL;
      GU-III, 14.3 +/- 10.0 ng/mL) than the controls (10.6 +/- 6.0 ng/mL) and the
      patients with DU (10.0 +/- 5.5 ng/mL), whereas no significant differences existed
      between the latter two. The ratio of PGI/PGII in GU-I (5.86 +/- 3.90) was
      significantly lower (P < 0.01) than any other group (controls, 8.83 +/- 4.70; GU
      II, 8.33 +/- 4.99; GU-III; 9.64 +/- 6.13; DU, 10.45 +/- 4.49), while patients
      with DU it was significantly higher (P < 0.01) than any other groups. These
      findings indicate that peptic ulcer is comprised of a heterogeneous group of
      diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527706
TI  - Secretory and biosynthetic responses of gastrin and somatostatin to acute changes
      in gastric acidity.
AB  - The activity of gastric parietal cells in terms of hydrochloric acid (HCl)
      secretion is regulated by the interaction of stimulatory substances (e.g.
      gastrin) and inhibitors (e.g. somatostatin) acting in an endocrine and paracrine
      mode, as well as luminal factors. In the present study the following parameters
      were measured: the synthesis (mRNA), storage (tissue peptide concentration) and
      secretion (plasma peptide concentration) of somatostatin and gastrin following
      short-term treatment of rats with pentagastrin (acid stimulant), secretin,
      omeprazole (reduces gastric acidity by inactivating gastric H/K ATPase) and the
      somatostatin analogue octreotide (reduces gastric acidity by inhibiting both the
      parietal cell and gastrin). The mRNA coding for H/K ATPase and carbonic anhydrase
      II (CA II), the two enzymes responsible for the generation of hydrogen ions from
      the parietal cell, were also quantitated. In response to octreotide, somatostatin
      peptide and mRNA levels in the fundus rose to 180 +/- 16% (P < 0.001) and 1073 +/
      356% (P < 0.05) of control, respectively. In contrast, octreotide caused a
      decrease in antral somatostatin peptide and its mRNA did not change
      significantly. No significant changes in synthesis, secretion or storage of
      gastrin were observed except for omeprazole induced hypergastrinaemia (580 +/-
      76%, P < 0.001). H/K ATPase and CA II mRNA were largely unaffected except for an
      increase in CA II mRNA following octreotide and a decrease in H/K ATPase mRNA
      after pentagastrin. These data support the concept of the differential control of
      antral and fundic somatostatin synthesis and provide evidence for a regulatory
      loop by which somatostatin can influence its own synthesis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8527707
TI  - Clinical and radiological pictures of hepatocellular carcinoma with intracranial
      metastasis.
AB  - Hepatocellular carcinoma (HCC) with extrahepatic spreading is not uncommon. In
      order to delineate the clinical and radiological pictures of HCC with
      intracranial metastasis, 33 documented cases were analysed. Eighteen had brain
      parenchymal metastasis without skull involvement; the other 15 cases disclosed
      skull metastasis with brain invasion. The underlying HCC are mainly of expanding
      (13/33, 39.4%) and multifocal (13/33, 39.4%) types. Eighteen cases (18/33, 54.5%)
      had mental changes not related to hypoglycaemia or hepatic encephalopathy.
      Eighteen cases (18/20, 90%) disclosed hyperdense mass lesions by non-contrast
      computed tomography (CT) scans and 17 cases showed homogeneous enhancement
      (17/22, 77.3%) by post-contrast CT images. In the non-skull involved group, five
      cases (5/12, 41.7%) disclosed ring-shape enhancement and 14 cases (14/16, 87.5%)
      had perifocal oedema, which were not seen in the skull involved group. Eight
      cases (8/33, 24.2%) presented as intracerebral haemorrhage. Twelve (12/33, 36.4%)
      died of brain herniation. Most (14/18, 77.8%) non-skull involved cases had
      simultaneous lung metastasis without bony metastasis, while the skull involved
      group often (10/15, 66.7%) disclosed extracranial bony metastasis without lung
      metastasis. The difference in extracranial metastasis was statistically
      significant (P < 0.05). The multivariate survival analysis disclosed that lower
      lactate dehydrogenase level (< or = 316 U/L, P = 0.029) and treatments (surgery
      or radiation, P = 0.001) were positively associated with longer survival. In
      conclusion, HCC with intracranial metastasis is symptomatic and life-threatening.
      Half the cases may come from pulmonary metastasis and the other half may be from
      bony metastasis. Brain irradiation or surgery can prolong their survival.

PMID- 8527708
TI  - Detection of hepatitis B virus precore stop codon mutants by selective
      amplification method: frequent detection of precore mutants in hepatitis B e
      antigen positive healthy carriers.
AB  - The precore region of hepatitis B virus (HBV) is indispensable for secretion of e
      antigen protein. Therefore, the precore stop codon mutants may play an important
      role in the process of e antigen seroconversion. However, the presence of the
      mutants in hepatitis B e antigen positive carriers has not been fully studied
      because of difficulties in detecting the mutants in the presence of large amounts
      of wild-type viruses. To overcome this, a sensitive method has been developed to
      detect the presence of G to A stop codon mutants at codon 28 of precore region.
      Primers for polymerase chain reaction (PCR) were devised to introduce restriction
      enzyme site Sty I for wild-type viruses and Dde I for the mutants. The
      amplification products with these primers were digested with Sty I to exclude the
      products from wild-type viruses. The remaining amplicon from precore mutants were
      re-amplified, and the presence of precore mutant was confirmed with Dde I
      digestion. The presence of precore mutants was examined in 61 HBV carriers by the
      method combining PCR and restriction enzyme digestion. Approximately 0.1% of
      precore mutant DNA among 10(6) copies of wild-type virus DNA was detectable by
      this method. The presence of the precore mutants was detected in seven of 10
      (70%) e antigen positive asymptomatic carriers, and in 29 of 36 (81%) e antigen
      positive patients with chronic liver diseases, and in all 15 (100%) anti-e
      antibody positive patients with chronic liver diseases. This study revealed that
      a small amount of the precore mutants was present in the majority of HBV
      carriers.

PMID- 8527709
TI  - Sonographic patterns of radiolucent gall-bladder stones for predicting successful
      shock-wave lithotripsy.
AB  - The aim of this study was to examine whether the sonographic patterns of
      gallstones are useful for predicting the outcome of piezoelectric shock-wave
      lithotripsy. Pretreatment analysis of gallstones based on our sonographic
      classification was conducted on 115 patients with radiolucent solitary stones of
      10-30 mm in diameter, monitored for at least a year after the first lithotripsy.
      All stones were categorized as type I with gradual attenuation of echoes: type
      Ia, the stone echo appears as a full moon, usually accompanied by comet-tail
      artifacts beyond the stone itself (n = 55); type Ib, the stone echo showing the
      anterior half of the stone, seen as a half moon (n = 29); and type Ic, the stone
      echo seen as a crescent (n = 31). The most complete fragmentation,
      'pulverization', was achieved at a significantly higher rate for type Ia (51%)
      than for type Ib (14%, P < 0.005) and type Ic (7%, P < 0.0001) after
      significantly fewer shock-waves (vs type Ib, P < 0.01; vs type Ic, P < 0.0001).
      The rate of complete clearance at 12 months after lithotripsy was significantly
      greater for type Ia (91%) than for type Ib (62%, P < 0.01) and type Ic (45%, P <
      0.0001). Comparison of the sonographic and computed tomography (CT) patterns of
      stones revealed a close relationship between the two: the vast majority (98%) of
      type Ia showed the iso- or hypo-dense, and the majority (90%) of type Ic the
      rimmed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527710
TI  - Efficacy of ursodeoxycholic acid in the treatment of patients with chronic
      hepatitis C.
AB  - A case-control study was conducted to evaluate the efficacy of ursodeoxycholic
      acid (UDCA) in the treatment of Chinese patients with chronic hepatitis C.
      Patients who failed to have sustained responses to interferon (IFN) therapy,
      refused to take IFN or were unsuitable for IFN treatment were enrolled into this
      study. The treatment group had 15 patients and they received UDCA 600 mg orally
      per day for 6 months. Another 15 patients with matched sex, age and initial serum
      alanine aminotransferase (ALT) levels were chosen as the control group. Three
      parameters (i.e. serum ALT levels, serum hepatitis C virus (HCV) RNA and serum
      cytokines) were measured before and after UDCA treatment. After the treatment
      period, the mean serum ALT levels in both groups were not significantly different
      (153.8 +/- 111.0 U/L vs 112.1 +/- 53.8 U/L, P > 0.05) and mean serum ALT level in
      the UDCA-treated group did not decrease after the treatment (pre-treatment vs
      post-treatment value: 139.1 +/- 73.1 U/L vs 153.8 +/- 111.0 U/L, P > 0.05). In
      addition, all of the patients with positive HCV RNA before treatment still had
      active HCV viraemia after the UDCA treatment. Also, the serum levels of
      interleukin-6 (IL-6) and the tumour necrosis factor-alpha (TNF-alpha) were not
      significantly different between the two groups before and after the treatment
      period. In conclusion, a regimen of UDCA as prescribed in the present study did
      not show obvious benefits in the treatment of Chinese patients with chronic
      hepatitis C.

PMID- 8527711
TI  - High prevalence of antibodies to recombinant CENP-B in primary biliary cirrhosis:
      nuclear immunofluorescence patterns and ELISA reactivities.
AB  - The purpose of the present study is to evaluate the centromeric pattern on human
      laryngeal tumour (HEp-2) cells by indirect immunofluorescent (IIF) test and to
      compare their reactivities with a newly developed recombinant centromere protein
      B enzyme linked immunosorbent assay (CENP-B ELISA) test using sera of antinuclear
      antibody (ANA)-reactive primary biliary cirrhosis (PBC) patients.
      Antimitochondrial antibody (AMA) subtypes (PDC-E2, BCOADC-E2, OGDC, protein X,
      and PDC-E1 alpha) by Western blot were also investigated to see whether they have
      any effect on the expression of CENP-B reactivities. A centromeric pattern
      (anticentromere antibody [ACA]) was detected in 11 of 25 (44%) PBC patients
      whereas CENP-B reactivity was found in 15 (60%) of them. There were some
      differences in IIF patterns and CENP-B reactivities. One PBC serum with
      indistinguishable ANA pattern reacted with CENP-B. Eight of 15 (53%) CENP-B
      reactive patients had other autoimmune-like disorders. Of 181 healthy sera, none
      was reactive for ACA either by IIF or by ELISA test. There was a correlation
      between ACA IIF and CENP-B ELISA titres (r = 0.824, P < 0.001). However, no
      correlation was observed between either CENP-B or AMA reactivities and/or between
      either autoantibodies or laboratory and histologic indices of PBC. These findings
      suggest that recombinant CENP-B ELISA appears to be more sensitive in identifying
      ACA than IIF, underlying its potential value as a screening test for the
      diagnosis of PBC complicated with other autoimmune-like disorders. The presence
      of multiple autoantibodies in PBC sera may reflect heterogeneous antigens
      recognition, and requires further study to identify target antigens at cellular
      and molecular levels.

PMID- 8527712
TI  - Chemosensitivity test for repeated arterial infusion chemotherapy by reservoir
      for unresectable hepatocellular carcinoma.
AB  - The experimental and clinical usefulness of a chemosensitivity test (Nuclear
      Damage Assay) was studied. Karyologic degenerative changes were observed as an
      indicator of drug sensitivity, in repeated arterial infusion chemotherapy (RAIC)
      using a reservoir for advanced hepatocellular carcinoma (HCC). In the
      experimental study, this sensitivity test was performed using five liver cell
      lines against 15 drugs. At the same time, the succinate dehydrogenase inhibition
      (SDI) test was also performed. Comparison of the results between these two tests
      gave a high consistency rate of 81%. Clinically, the karyologic sensitivity test
      was carried out in 135 patients with unresectable HCC. Drug sensitivity could be
      evaluated in as many as 89% of the total 135 patients. Of the patients, 43
      received RAIC on an outpatient basis via a subcutaneously implanted reservoir.
      The objective response of RAIC on tumours of the 43 patients was evaluated as
      complete response, partial response, in 3 (9%) and 8 (23%) in 35 patients treated
      with positive drugs (positive group), and as 0 (0%) and 0 (0%) of 8 patients
      treated with negative drugs (negative group), respectively. As regards the
      prognosis, 1 year and 1.5 year survival rates were 70 and 45% in the positive
      group, and 42 and 0% in the negative group, respectively. As objective response
      in the positive group tended to be better than that in the negative group, and
      prognosis in the positive group was significantly better than that in the
      negative group, this sensitivity test appears to contribute to the improvement of
      therapeutic results if used to select drugs suitable for RAIC for advanced HCC.

PMID- 8527713
TI  - Effect of hepatitis C antibody screening in blood donors on post-transfusion
      hepatitis in Taiwan.
AB  - A national screening programme for antibody to hepatitis C virus (HCV) in blood
      donors in Taiwan began in July 1992 using a second-generation immunoassay. To
      study the impact of this screening on post-transfusion hepatitis in Taiwan, a
      prospective study on post-transfusion hepatitis, that was started in 1987, was
      continued. As of June 1994, 245 patients who received a blood transfusion after
      July 1992 had completed a follow-up period for more than 6 months post
      transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion
      hepatitis. The hepatitis in six cases could not be attributed to infection by
      hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus
      (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All
      seven patients recovered in 6 months without development of chronicity, and the
      mean peak alanine aminotransferase level was lower compared with that of the
      cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that
      the current anti-HCV screening has effectively interrupted HCV transmission
      through blood transfusion in Taiwan.

PMID- 8527714
TI  - Effect of changes in vascular tone on the haemodynamic characteristics of the
      portal vascular bed of the isolated perfused rat liver.
AB  - The effect of altered vascular tone on the haemodynamic characteristics of the
      intrahepatic portal vascular bed was studied in the isolated perfused rat liver
      preparation. The relationship between portal venous inflow (Q) and portal
      perfusion pressure (P) was determined in the presence of a maximally effective
      concentration of a vasoconstrictor agent (noradrenaline, NAmax, 3 x 10(-5)mol/L),
      an intermediate concentration (NAmed, 1 x 10(-6)mol/L) or a vasodilator agent
      (papaverine, PAP, 6 x 10(-4)mol/L). At flow rates greater than 20 mL/min, the
      pressure-flow relationship could be regarded as linear (P < 0.001), with mean
      values for the extrapolated intercept with the pressure axis (Po) of 6.8 +/- 0.9
      mmHg for NAmax, 4.5 +/- 0.5 mmHg for NAmed, and 1.65 +/- 0.05 mmHg for PAP
      treated preparations. Over the full flow range (0-70 mL/min), in both NA- and PAP
      treated preparations, portal vascular conductance (G = Q/P) was related directly
      to perfusion pressure. Thus, G = C.P, where C is a constant (mean values for
      NAmax, NAmed, and PAP-treated preparations were 0.0090 +/- 0.0020, 0.023 +/-
      0.005, and 0.26 +/- 0.02 mL/min per g per mmHg2, respectively). It is concluded
      that both C and Po may be useful indices of tone in the isolated perfused rat
      liver, and that analysis of hepatic portal haemodynamics in this manner may have
      considerable practical value in studies of the action of vasoactive agents.

PMID- 8527715
TI  - Helicobacter pylori: more than 10 years on and still catchy.

PMID- 8527716
TI  - Leucocyte-endothelial interactions in the vasculature following inflammation of
      the gastric mucosa.

PMID- 8527717
TI  - Hepatitis C and liver transplantation.
AB  - Hepatitis C virus (HCV) is important to the liver transplant recipient for
      several reasons. First, chronic HCV infection is a frequent cause of end-stage
      liver disease in North America and Europe, where the majority of liver
      transplants are performed. Second, recurrence of HCV after liver transplantation
      is almost universal so that many liver transplant recipients with and without
      overt hepatitis are viraemic. Third, HCV infection in the organ donor and/or in
      the blood transfused in the peri-transplant period make acquisition of HCV
      possible. Finally, liver transplantation for chronic HCV infection represents a
      major financial burden to the health-care system in the USA and worldwide.
      Histological hepatitis not due to HBV or cytomegalovirus (CMV) is present in 14
      35% of allografts from patients undergoing liver transplantation, and the
      majority of this is due to HCV infection. HCV infection recurs post-transplant in
      almost all patients with pre-transplant infection. Proof that HCV does recur has
      been provided by the sequencing of the hypervariable domain of the E2/NS1 region.
      The magnitude of HCV infection is underestimated by using serological assays in
      this immunosuppressed population. Using the b-DNA assay, HCV-RNA levels have been
      shown to increase in patients with recurrent infection. The long-term
      consequences remain to be defined but post-transplantation HCV infection is
      generally much less devastating than post-transplantation HBV infection, and many
      patients have clinically silent disease. It is likely that a carrier state exists
      in immunosuppressed transplant recipients since high HCV-RNA levels occur in the
      absence of liver damage. In one study, 1, 2 and 3 year patient survival rates
      were shown to be comparable in patients with chronic active HCV infection and
      with cryptogenic cirrhosis (94, 89 and 87%, and 84, 84 and 73%, respectively). A
      more recent study from the University of Pittsburgh which compared the outcome of
      a larger number of HCV-infected patients (n = 237) with a large number of control
      patients with non-viral disease (n = 801), showed that indeed HCV infection does
      impact negatively on both patient and graft survival (1, 2 and 3 year patient
      survival in the study and control groups of 78, 68 and 66% and 84, 82 and 78%,
      respectively, P = 0.001). Undoubtedly with time, the full impact of recurrent HCV
      infection will become apparent, although short-term survival is sufficiently good
      to warrant continued transplantation of this group of patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8527718
TI  - Endoscopic injection sclerotherapy of bleeding duodenal varices.
AB  - Bleeding from duodenal varices is a rare finding in patients with liver
      cirrhosis. We report a 43 year old male with alcoholic liver cirrhosis who
      presented with upper gastrointestinal bleeding. Panendoscopy identified,
      prominent tortuous varices over the second portion of duodenum with spurting of
      blood. At first, the varices were treated successfully with sodium tetradecyl
      sulfate and bleeding stopped. Consequent endoscopic sclerotherapy was done 1 week
      later. The varices almost disappeared 2 weeks after the second endoscopic
      sclerotherapy and the patient was in good condition following this.

PMID- 8527719
TI  - Granulomatous hepatitis associated with scrub typhus.
AB  - A 56 year old patient with scrub typhus infection having unusual presentation of
      hepatic injury resembling acute hepatitis is described. The clinical features of
      fever, headache, eschar, lymphadenopathy, lymphocytosis and high Rickettsia
      tsutsugamushi immunofluorescence titres confirmed the diagnosis of scrub typhus.
      Acute hepatitis was proven by hepatic biochemical tests and liver biopsy. The
      patient had a complete recovery soon after antibiotic treatment. The presentation
      of this case suggests that scrub typhus infection should be included in the list
      of differential diagnosis of acute hepatitis or granulomatous hepatitis, at least
      in the Asian Pacific region where scrub typhus still prevails.

PMID- 8527720
TI  - More on lymphoma and chronic liver disease.

PMID- 8527721
TI  - Amyloidosis, advanced glycation end products and Alzheimer disease.

PMID- 8527722
TI  - Reticulospinal neurones provide monosynaptic glycinergic inhibition of spinal
      neurones in lamprey.
AB  - In lamprey, distinct groups of reticulospinal neurones utilize different
      neurotransmitters such as glutamate or serotonin. The present study demonstrates
      that a group of reticulospinal neurones inhibit their target neurones by an
      action on glycine receptors. Simultaneous intracellular recordings from a
      reticulospinal neurone and spinal target neurone shows that the former may evoke
      an IPSP in the latter. These IPSPs are elicited at a constant latency and
      amplitude, and follow high frequency stimulation (100 Hz). Furthermore, the IPSPs
      are maintained when the excitatory amino acid synaptic transmission is blocked,
      suggesting that the effects are not elicited via a powerful disynaptic pathway.
      These data taken together establish the monosynaptic nature of the pathway. IPSPs
      elicited from single reticulospinal neurones or from electrical stimulation of
      the reticular formation are suppressed by administration of strychnine,
      suggesting that glycine is the neurotransmitter of these inhibitory
      reticulospinal neurones.

PMID- 8527723
TI  - Mesolimbic dopamine terminals and locomotor activity induced from the subiculum.
AB  - The role of the mesolimbic dopamine terminals in the nucleus accumbens in the
      initiation of locomotion in rats was studied. Locomotor activity was initiated by
      activation of the excitatory input from the ventral subiculum to the nucleus
      accumbens with NMDA. Measurements of locomotor activity, induced by unilateral
      administration of NMDA into the ventral subiculum, were compared before and after
      destruction of the mesolimbic dopamine terminals in the nucleus accumbens. The
      dopamine terminals were destroyed by injection of 6-OHDA into the ventral
      tegmental area which projects to the nucleus accumbens. Injection of NMDA into
      the ventral subiculum caused an almost four-fold increase in locomotor activity.
      However, this increase was abolished after the destruction of the mesolimbic
      dopamine terminals in the nucleus accumbens. The results suggest that the
      mesolimbic dopamine terminals are essential in transmitting subicular signals to
      the output neurones within the nucleus accumbens.

PMID- 8527724
TI  - Human prefrontal lesions increase distractibility to irrelevant sensory inputs.
AB  - Neurological patients with focal lesions in either the dorsolateral prefrontal
      cortex, temporal-parietal junction or the posterior hippocampus, and control
      subjects, were tested on a task requiring short-term retention of environmental
      sounds. Subjects had to indicate whether initial and subsequent test sounds were
      identical in two conditions. The initial and test sounds were separated by either
      a silent period varying from 4 to 12.6 s (no-distractor condition) or a series of
      irrelevant tones (distractor condition). Prefrontal patients were significantly
      impaired by distractors at all delays, hippocampal patients were impaired only at
      longer delays, while temporal-parietal patients performed similar to controls.
      The findings suggest that dorsolateral prefrontal cortex is crucial for gating of
      distracting information during delay tasks.

PMID- 8527725
TI  - Excitotoxic insult due to ibogaine leads to delayed induction of neuronal NOS in
      Purkinje cells.
AB  - Ibogaine causes degeneration of Purkinje cells (PKCs), presumably via activation
      of neurons in the inferior olive leading to release of glutamate at climbing
      fiber terminals. Following ibogaine administration, some Purkinje cells express
      NADPH-diaphorase and neuronal NOS (nNOS), neither of which is present normally in
      these cells. The induction of NOS is delayed in onset, dose-related, and detected
      in neurons adjacent to degenerated PKCs. The results demonstrate that nNOS
      induction can follow excitotoxic neuronal injury or perturbation. However, NO is
      unlikely to participate in the initial phase of PKC damage. Both the late
      induction of nNOS and the spatial relationship between damaged and nNOS
      expressing PKCs are consistent with a role for NO in either neuronal recovery or
      delayed cell death following excitotoxic injury.

PMID- 8527726
TI  - Neuroprotective effects of omega-Aga-IVA against in vitro ischaemia in the rat
      hippocampal slice.
AB  - Excessive accumulation of Ca2+ in neurones and glutamate release are involved in
      neuropathological processes, including ischaemia. We investigated the
      neuroprotective effects of the Ca2+ channel antagonist, omega-Aga-IVA, in CA1
      pyramidal neurones in rat hippocampal slices following an in vitro hypoxic
      hypoglycaemic insult. Following this insult, evoked post-synaptic response
      amplitudes decreased from 3.7 +/- 0.5 mV to 0.6 +/- 0.2 mV and the CA1 neurones
      appeared dead using a live/dead fluorescence assay with confocal microscopy.
      Slices treated with 200 nM omega-Aga-IVA had evoked response amplitudes not
      significantly different from control (3.3 +/- 0.5 mV) and the CA1 neurones
      appeared viable using the live/dead fluorescence assay. The neuroprotective
      efficacy of omega-Aga-IVA suggests that omega-Aga-IVA-sensitive Ca2+ channels
      participate in ischaemic neuronal death and constitute a potential target of
      therapeutic intervention.

PMID- 8527727
TI  - Regional difference of high voltage-activated Ca2+ channels in rat CNS neurones.
AB  - The diversity of high voltage-activated (HVA) Ca2+ channels in rat CNS neurones
      was investigated with the nystatin perforated patch recording configuration. The
      neurones were freshly dissociated from rat substantia nigra, ventromedial
      hypothalamus, tuberomammillary nucleus, nucleus tractus solitarius, hippocampal
      CA1 region and cerebellum. Five different types of HVA Ca2+ channels were
      distinguished pharmacologically; dihydropyridine sensitive L-type, omega
      conotoxin-GVIA sensitive N-type, omega-agatoxin-IVA sensitive P-type, omega
      conotoxin-MVIIC sensitive Q-type, and R-type which is insensitive to these
      organic Ca2+ antagonists. The results showed clearly that the five subtypes of
      HVA Ca2+ channels differ considerably in their distribution among various CNS
      regions.

PMID- 8527728
TI  - Effects of thalamic and nucleus basalis infusions of nicotine on cortical EEG.
AB  - The present study was designed to investigate the hypothesis that nicotine may
      act via thalamic and basal forebrain nicotinic acetylcholine receptors to
      suppress neocortical high voltage spindling and slow waves in awake rats. Loca
      microinfusions of a nicotinic acetylcholine receptor agonist (nicotine 3, 10 and
      30 micrograms) or antagonist (mecamylamine 10 micrograms) into the vicinity of
      the basal forebrain cholinergic projection neurones of the nucleus basalis had no
      effect on cortical EEG waves. However, nicotine (3, 10 and 30 micrograms)
      microinfusions into the thalamus decreased high voltage spindles and
      desynchronized non-spindling EEG waves in the cortex. This suggests that
      nicotinic acetylcholine receptor active drugs may modulate thalamocortical
      oscillations and desynchronize EEG waves via brain stem cholinergic projections
      at the thalamus.

PMID- 8527729
TI  - Nitric oxide modulates blood-brain barrier permeability during infections with an
      inactivated bacterium.
AB  - The objective of the present investigation was to study the involvement of NO in
      regulating the permeability of the blood-brain barrier (BBB) during infections,
      since NOS is known to be induced following infections. The administration of
      inactivated Escherichia coli (a source of lipopolysaccharide) or poly (I:C), an
      interferon inducer, to rats increased the permeability of BBB significantly. This
      increase was found to be potentiated in the presence of L-arginine, a substrate
      for NOS, while D-arginine had no such effect. N-nitro L-arginine methyl ester, an
      inhibitor of NOS, and dexamethasone, an inhibitor of NOS induction, blocked the
      E. coli-induced effects. These results suggest that during infections, NOS
      inductions causes the release of large quantities of NO, resulting in increased
      BBB permeability.

PMID- 8527730
TI  - Chronic alcohol exposure decreases brain intracellular free magnesium
      concentration in rats.
AB  - Phosphorus magnetic resonance spectroscopy was used to determine effects of acute
      and chronic alcohol exposure on brain intracellular free magnesium concentration
      (Mgf) and bioenergetic state in rats. Acute alcohol (3 mg kg-1, i.p.) resulted in
      a transient ( < 2h) decline in brain Mgf and cytosolic phosphorylation ratio, and
      an increase in mitochondrial oxidative capacity. In contrast, chronic exposure to
      alcohol for 30 days by vapour inhalation resulted in a depletion of brain Mgf
      with no significant change in bioenergetic parameters. Subsequent exposure of
      chronically alcoholised rats to an acute dose of alcohol (3 g kg-1) did not
      result in any further changes. We conclude that chronic exposure to alcohol
      results in a depletion of brain Mgf and compromised bioenergetic regulation.

PMID- 8527731
TI  - Different neural systems for the recognition of animals and man-made tools.
AB  - Using positron emission tomography, we mapped brain activity in normal volunteers
      during the recognition of visual stimuli representing living (animals) and non
      living (artefacts) entities. The subjects had to decide whether pairs of visual
      stimuli were different representations of the same object, or different objects.
      Animal recognition was associated with activations in the inferior temporo
      occipital areas, bilaterally, whereas artefact recognition engaged a
      predominantly left hemispheric network, involving the left dorsolateral frontal
      cortex. These findings, which concur with clinical observations in neurological
      patients, provide in vivo evidence for a fractionation of the neural substrates
      of semantic knowledge in man.

PMID- 8527732
TI  - Increased cerebrospinal fluid concentration of nitrite in Parkinson's disease.
AB  - The concentration of nitrite, a metabolite of nitric oxide (NO), was increased in
      the cerebrospinal fluid (CSF) of untreated patients with Parkinson's disease and
      in patients treated with L-DOPA in comparison with a group of patients without
      dopaminergic dysfunction. There was no difference in the concentration of L
      arginine (ARG), a precursor of NO, between the groups. There was a highly
      significant, linear relationship between the concentration of nitrite and ARG in
      the CSF suggesting that the production of NO is dependent on the availability of
      ARG. The results support the possibility that production of NO is increased in
      the brain in Parkinson's disease.

PMID- 8527733
TI  - Neural correlates of gap detection and auditory fusion in cat auditory cortex.
AB  - Responses were recorded from 130 single neurones in the primary auditory cortex
      of 12 ketamine-anaesthetized cats in response to double-click stimuli, to a /ba/
      /pa/ phoneme continuum and to gaps inserted early (after 5 ms) and late (after
      500 ms) in a 1 s duration noiseburst. Stimulus levels were between 45 and 75 dB
      SPL. Neural detection threshold for the 'late gap' was less than 5 ms. For the
      double click and 'early gap' stimuli thresholds were between 40 and 50 ms,
      whereas the phoneme continuum threshold for voice-onset-time (VOT) was between 10
      and 25 ms. The 'late gap' and VOT thresholds are similar to psychophysical gap
      detection and the /ba/-/pa/ categorical perception boundary respectively.

PMID- 8527734
TI  - Further evidence on the contribution of GABAA receptors to the GABA-mediated
      inhibition of medial vestibular nucleus neurones in vitro.
AB  - The present study investigated the electrophysiological effects of the selective
      and potent GABAA receptor agonist, isoguvacine, on guinea-pig medial vestibular
      nucleus (MVN) neurones in brainstem slices. The results confirm that many MVN
      neurones have GABAA receptors and that, even at concentrations as low as 10(-8)
      M, GABA is capable of exerting a powerful inhibitory effect on these neurones via
      GABAA receptors. The finding that > 50% of neurones did not respond to
      isoguvacine, even at concentrations of 10(-6) M, suggested that only a specific
      subset of MVN neurones have GABAA receptors. Since many type I MVN neurones are
      believed to have postsynaptic GABAA receptors, it is possible that selective
      agonists such as isoguvacine may be useful in identifying type I neurones in
      vitro.

PMID- 8527735
TI  - Modulation of somatosensory evoked magnetic fields by sensory and motor
      interferences.
AB  - Modulatory influences of skilled exploratory finger movements on somatosensory
      evoked magnetic fields evoked by median nerve stimulation were investigated in
      six healthy subjects using a whole head magnetometer (MEG) system. The
      exploratory finger movements caused major changes in the somatosensory evoked
      fields. The most prominent effect was a reversal of the dipolar magnetic field
      around 30 ms after median nerve stimulation. Similar but less pronounced effects
      were exerted by repetitive finger movements and tactile stimulation of the hand.
      A dipole analysis and super-imposition of resulting sources on individual MRI
      scans showed that all somatosensory evoked fields up to 60 ms after stimulation,
      and the modulation of these responses were located in the primary somatosensory
      cortex (SI).

PMID- 8527736
TI  - Effect of TENS-like stimulation on C afferent-induced c-fos expression in the rat
      spinal cord.
AB  - Transcutaneous electrical nerve stimulation (TENS) has been widely used to
      relieve pain. This study examined the effect of TENS-like stimulation on primary
      C afferent-induced c-fos expression in the rat spinal dorsal horn. Fos-like
      immunoreactivity (FLI) evoked by excitation of C fibres of the tibial nerve was
      found ipsilaterally in laminae I-VIII and X of the spinal cord. The greatest
      number of FLI neurones was located in the medial half of laminae I-II0 and V at
      L5. When TENS-like stimulation (100 Hz) was applied proximally to the same tibial
      nerve, the number of FLI neurones by C afferents was reduced remarkably in
      ipsilateral laminae I-II0 and IV-VII. The results suggest that TENS stimulation
      induced reduction of c-fos expression may reflect an inhibition of spinal
      nociception.

PMID- 8527737
TI  - Hypertension inhibits noxious-evoked c-fos expression in the rat spinal cord.
AB  - The effect of hypertension on spinal induction of the c-fos proto-oncogene
      following noxious mechanical stimulation of the skin was studied in the rat. The
      occlusion of renal artery raised blood pressure steeply, reaching 52% over
      initial values. Oral administration of NG-nitro-L-arginine methyl ester provoked
      a gradual increase in blood pressure which reached up to 62%. The numbers of
      spinal dorsal horn Fos-immunoreactive nuclei were reduced to 66% and 38% of
      controls in animals with renal- and pharmacologically-induced hypertension,
      respectively. These data indicate that hypertension is accompanied by an
      inhibition of spinal nociceptive neurones which probably accounts for the
      hypoalgesia observed in hypertensive subjects. They further suggest an influence
      by the rate of increase of blood pressure on the level of spinal inhibition.

PMID- 8527738
TI  - Glutathione suppresses spontaneous activity in the frog spinal cord.
AB  - Spontaneous electrical activity in the isolated hemisected frog spinal cord
      increased in the presence of the SH reductant dithiothreitol (DTT) was reversibly
      suppressed by the oxidant 5-5'-dithio-bis-(2 nitrobenzoic acid) (DTNB) and was
      irreversibly suppressed by the sulphydryl modifying agents N-ethyl-maleimide
      (NEM) and monobromotrimethylammonio bimane. Glutathione (GSH), an important
      natural low molecular weight thiol, reversibly suppressed spontaneous activity.
      Cords pretreated with glutathione and successively exposed to NEM or bimane
      maintained their normal electrical activity. This indicates that GSH had
      interacted with the exposed sulphydryls and prevented their reaction with NEM or
      bimane. Incubation with bimane resulted in fluorescence-labelled neurones in the
      dorsal and ventral horns, whereas samples pretreated with NEM or with GSH were
      not labelled. Neurones appeared again fluorescent in cords preincubated with GSH
      and sequentially exposed to NEM or bimane. Both electrophysiological and
      histochemical methods indicate that exposed membrane sulphydryls are involved in
      the genesis and/or modulation of spontaneous electrical potentials.

PMID- 8527739
TI  - Ectopic expression of a bacterial lacZ gene in the limbic system of transgenic
      mice.
AB  - In three independent lines of transgenic mice, a 3.6 kb 5'-flanking sequence of
      the uroplakin II gene consistently drives the ectopic expression of a bacterial
      lacZ reporter gene in brain, in addition to its specific expression in the
      suprabasal layers of the urothelium. The ectopic expression in brain is
      especially noteworthy insofar as it is confined to structures comprising the
      limbic system. These findings provide additional evidence that the cells forming
      such functional systems share specific biochemical properties, and also indicate
      that this promoter may be useful as a tool for studying the effects of
      overexpression of proteins in anatomically and functionally defined central
      nervous system pathways.

PMID- 8527740
TI  - Fenfluramine-induced c-fos in the striatum and hypothalamus: a tract-tracing
      study.
AB  - Systemic administration of DL-fenfluramine (20 mg kg-1), an indirect serotonergic
      agonist, induced widespread FOS-like protein in the rat caudate putamen (CPu),
      paraventricular nucleus (PVn) of the hypothalamus and several intralaminar
      thalamic nuclei. To ascertain whether the dopaminergic nigrostriatal system
      coordinated transcriptional effects on the CPu, discrete microinjections of
      dextran into the substantia nigra (cell group A9) were evaluated for retrograde
      axonal transport. The protein product was induced preferentially in medium-sized
      spiny nerve cells of the CPu. Dextran microinjections into the PVn demonstrated
      that perikarya bearing FOS-like protein projected their extensions directly to
      thalamic nuclei and indirectly to immunopositive neurons of the striatum. The
      significance of these latter results is discussed in terms of a possible
      dopaminergic mechanism.

PMID- 8527741
TI  - Two types of calcium channels sensitive to omega-agatoxin- TK in cultured rat
      hippocampal neurones.
AB  - We characterized the electrophysiological properties of calcium channels in
      cultured rat hippocampal neurones using omega-agatoxin-TK (omega-Aga-TK) and
      compared them with those of the P-type channel and the BI (alpha 1A) channel
      which resembles the Q-type channel. Two types of omega-Aga-TK-sensitive calcium
      channels were detected in hippocampal neurones. The first type showed slow
      inactivation, high sensitivity to omega-Aga-TK and low reversibility from omega
      Aga-TK-induced block, resembling the P-type channel. The second type showed fast
      inactivation, low sensitivity to omega-Aga-TK and high reversibility from omega
      Aga-TK-induced block. These results suggest that the second type of calcium
      channel (Q-type-like) plays a prominent role in the hippocampal synaptic
      transmission.

PMID- 8527742
TI  - Effects of interleukin-1 beta and interleukin-2 on amino acids levels in mouse
      cortex and hippocampus.
AB  - We measured the levels of glutamine, aspartic acid, glutamic acid and GABA in
      cortex and hippocampus of mice acutely treated with i.p. human recombinant
      interleukin-2 (IL-2) or human recombinant interleukin-1 beta (IL-1 beta).
      Administration of IL-2 (5.0 micrograms kg-1) induced a slight but statistically
      significant increase in glutamine concentrations in both brain areas, while
      similar administration of IL-1 beta (20 micrograms kg-1) significantly reduced
      the hippocampal levels of glutamine, glutamic acid and GABA. Our data suggest
      that brain amino acid pathways are involved in the central modifications induced
      by IL-1 beta.

PMID- 8527743
TI  - Electrophysiological correlates of visual search asymmetry in humans.
AB  - Visual evoked potentials (VEPs) were recorded during a visual search task to
      evaluate parallel and serial models of visual processing. A target stimulus
      elicited a discrete posterior negative wave in the 150-300 ms latency range.
      Furthermore, there was a close correlation between the search performance and the
      activity of the negative wave. When the target had a unique feature, neither the
      search time nor the characteristics of the negative wave was affected by the
      number of items in display. However, when the target lacked a unique feature,
      both the search time and the latency of the negative wave increased with the
      number of items. These results were consistent with a claim that an object with a
      unique feature is detected preattentively.

PMID- 8527744
TI  - Pregnenolone sulfate antagonizes dizocilpine amnesia: role for allopregnanolone.
AB  - Pregnenolone (PREG) is metabolized in brain to progesterone (PROG), 5 alpha
      dihydroprogesterone (5 alpha-DHP) and allopregnanolone (ALLO). Infusion of
      adrenalectomized/castrated rats with PREG sulfate prevented the cognition deficit
      elicited by the ionotropic glutamate receptor antagonists, dizocilpine and
      CPPene. Using a new gas chromatographic/mass-spectrometric method, we
      demonstrated that PREG sulfate infusion markedly increased the PREG, PROG, 5
      alpha-DHP and ALLO brain content. The increase in 5 alpha-DHP and ALLO, but not
      PREG or PROG content and the antagonism of dizocilpine amnesia observed by
      injecting rats with PREG sulfate was reversed by inhibiting the conversion of
      PROG to 5 alpha-DHP with the 5 alpha-reductase blocker SKF 105111. We and others
      have shown that ALLO potently modulate GABAA receptor function whereas 5 alpha
      DHP fails to induce rapid changes in neurotransmitter receptor function. Thus it
      is possible to suggest that the increase in the brain content of ALLO, rather
      than 5 alpha-DHP, mediates the effect of PREG sulfate on dizocilpine- or CPPene
      induced cognition deficit.

PMID- 8527745
TI  - Effects of photoperiod on food-storing and the hippocampus in birds.
AB  - Birds that store food have a relatively large hippocampus compared to non-storing
      species. The hippocampus shows seasonal differences in neurogenesis and volume in
      black-capped chikadees (Parus atricapillus) taken from the wild at different
      times of year. We compared hippocampal volumes in black-capped chickadees
      captured at the same time but differing in food-storing behaviour because of
      manipulations of photoperiod in the laboratory. Differences in food-storing
      behaviour were not accompanied by differences in the volume of the hippocampus.
      Hippocampal volumes also did not differ between two groups of a non-food-storing
      control species, house sparrows (Passer domesticus), exposed to the same
      conditions as the chickadees.

PMID- 8527746
TI  - The expression of m1-m3 muscarinic receptor mRNAs in rat brain following REM
      sleep deprivation.
AB  - We used in situ hybridization histochemistry to study the effects of REM sleep
      deprivation on m1-m3 muscarinic receptor mRNA expression in the rat brain. REM
      sleep deprivation for 72 h did not affect m1 receptor mRNA expression. However,
      we found significantly increased m3 receptor mRNA expression in the pontine
      nuclei and nucleus accumbens-bed nucleus of the stria terminalis region of REM
      sleep-deprived rats compared with controls. Paradoxically, we found significantly
      decreased m2 receptor mRNA expression in the pontine nuclei of REM sleep-derived
      rats vs controls. The present findings implicate these structures in the
      cholinergic effector pathways of REM sleep, although the type and magnitude of
      the effects of these structures on REM sleep may vary with different receptor
      subtypes.

PMID- 8527747
TI  - [Functional NMR tomography of the CNS: research or diagnostic routine?].

PMID- 8527748
TI  - Imaging of chondrosarcoma with histopathological and prognostic correlation. An
      analysis of 49 cases mainly based on plain film radiography.
AB  - PURPOSE: To investigate the course of chondrosarcoma in relation to radiographic
      and histopathologic findings. MATERIAL AND METHODS: 49 consecutive patients seen
      during an 11-year-period were analysed, including re-evaluation of their
      radiographic and histopathologic material. RESULTS: Forty-two patients had
      radiographic changes typical for cartilaginous tumours, in 37 with malignant
      stigmata. Seven patients had malignant changes not typical for chondrosarcoma. By
      histopathologic grading 16 patients had grade I, 17 grade II and 16 grade III
      tumours. Six of the grade II-III tumours were histopathologic variants
      (mesenchymal, dedifferentiated or myxoid chondrosarcomas). Surgical removal of
      the tumour was performed in 42 patients, 41 of whom were followed up for 0.4-11.4
      years (median 3.8 years). Local recurrence occurred in 7 patients, and 11
      patients developed metastases. Ten patients, 4 with local recurrence and
      metastases, and 6 with metastases only were dead at the end of the follow-up. The
      actuarial 5-year overall survival rate was 64%. The occurrence of local
      recurrence, metastases and death was found to be related to the histopathologic
      grades II and III. Atypical radiographic features only occurred in grade II-III
      tumours and were related to metastases and death, but not to local recurrence.
      CONCLUSION: Atypical radiographic findings were related to high-grade malignancy
      and poor prognosis.

PMID- 8527749
TI  - [Bronchiectasis and infection incidence in alpha 1-antitrypsin deficiency. The
      value of high-resolution computed tomography].
AB  - PURPOSE of this study was to determine the prevalence of bronchiectasis in
      patients suffering from alpha-1-antitrypsin deficiency and to compare its extent
      with the frequency of infections. MATERIAL AND METHODS: High-resolution CT
      examinations (HRCT) of 23 patients with alpha-1-antitrypsin deficiency were
      retrospectively assessed for extent, severity and localisation of bronchiectasis,
      bronchial wall thickening and extent of emphysema. Chest radiographs and clinical
      records were available for correlation. RESULTS: HRCT scans showed bronchiectasis
      in 14 of 23 patients, bronchial wall thickening in 3/14, and panlobular emphysema
      in 23/23. Chest radiographs showed bronchiectasis in 4/23 patients. Only two of 9
      patients without bronchiectasis had a history of infections; all 8 patients with
      multiple bronchiectasis had a history of recurrent infections. CONCLUSION:
      Bronchiectasis is a common finding in alpha-1-antitrypsin deficiency, and is
      associated with recurrent infections. HRCT is superior to chest radiography as an
      indicator for the risk of infection in these patients.

PMID- 8527750
TI  - [An anatomically adapted variation of the tube current in CT. Studies on
      radiation dosage reduction and image quality].
AB  - PURPOSE: To assess the impact of a method for anatomically adapted tube current
      variation. The resulting CT image quality was evaluated quantitatively and
      qualitatively. METHODS: CT scans of 100 patients were performed with a constant
      tube current (Group 1) and another 100 patients with an anatomically adapted tube
      current (Group 2). The CT tube current was varied during a 360 degrees tube
      rotation reflecting the measured density values extracted from two perpendicular
      scout views. The standard deviation of densities of defined regions was measured.
      The image quality was ranked (1 = non-diagnostic-5 = excellent) by three
      radiologists. RESULTS: The effective tube current could be reduced by an average
      of 8.9% (0-20.4%). The mean tube current reduction depended on the body region:
      pelvis (13.2%), abdomen (8.4%) and thorax (3.3%). The image quality was not
      significantly reduced in Group 2. CONCLUSION: The method for anatomically adapted
      tube current variation leads especially in the pelvis to a significant mAs
      reduction without considerable loss of image quality.

PMID- 8527751
TI  - [A bimetal anode with tungsten or rhodium? Comparative studies on image quality
      and dosage requirement in mammography].
AB  - PURPOSE: The impact of different anode materials (tungsten and rhodium) on
      spatial resolution, image contrast and radiation exposure was studied. MATERIALS
      AND METHODS: Two mammographic systems providing bimetal x-ray tubes (Mo/W and
      Mo/Rh) were compared by imaging a breast radiography phantom with additional
      acrylic plates from 3 to 8 cm thickness. Spatial resolution was evaluated using a
      line bar pattern. Image contrast was assessed by measuring the ratio of optical
      densities in a acrylic step-wedge. The entrance dose was measured with a low
      energy ionisation chamber. RESULTS: The spatial resolution was about 13 lp/mm
      regardless of the beam quality. The image contrast depended substantially on the
      thickness. A similar image contrast was found with Mo/Mo, Mo/Rh and Rh/Rh for
      simulated breast thicknesses of 4 to 6 cm and with Rh/Rh and W/Rh for 7 cm. In
      comparison to Mo/Mo the dose reduction was significant for Mo/Rh (35%), Rh/Rh
      (50%) and W/Rh (60%). CONCLUSIONS: Bimetal x-ray tubes provide optimal conditions
      for screen film mammography of both normal and dense breasts, allowing good
      contrast and dose reduction by using the adequate anode/filter-combination.

PMID- 8527752
TI  - [The diagnostic value of digital and conventional imaging in intravenous
      urography].
AB  - PURPOSE: To compare image quality of digital luminescence radiography with
      conventional film-screen techniques during excretion urography. Four field tests
      and ROC analysis for determining diagnostic value. MATERIAL AND METHOD: 135
      patients were included in a prospective study. Three independent observers judged
      the five minute (59 cases) or ten minute (76 cases) films after contrast
      injection using digital images as well as corresponding conventional images (five
      minutes-76 cases, ten minutes-59 cases). RESULTS: The digital technique provided
      better information concerning the renal parenchyma, the soft tissues and bone
      structures. Contrast enhanced detail was demonstrated equally well by both
      systems. The two systems had similar sensitivity but digital radiography showed
      higher specificity.

PMID- 8527753
TI  - [The MRT of malignant tumors of the oral cavity and oropharynx with frequency
      selective and inversion-recovery fat-signal suppression].
AB  - PURPOSE: Evaluation of frequency-selective fat saturation (FS) and Short-Tau
      Inversion-Recovery (STIR) fat suppression (FU) in MRI of patients with malignant
      tumours of the oral cavity or oropharynx. METHODS: Twenty patients with biopsy
      proven squamous cell carcinoma of the oral cavity or oropharynx were examined by
      MRI at 1.0 T. A T2-weighted TSE-sequence with and without STIR-FU and a T1
      weighted SE-sequence with and without FS were compared in axial slices. RESULTS:
      STIR-FU was successful in all and FS in 29/33 (87.9%) of the examinations. When
      visualisation and delineation of tumours were ranked on a four-point scale (0-3),
      respective mean values for images without/with FU or FS of 1.9 and 2.6 for T2
      TSE, 1.4 and 1.3 for T1-SE without contrast media administration (CM) and 2.0 and
      2.5 with CM were found. Signal/noise-ratios were inferior with FU and FS, but the
      tumour/muscle intensity ratio in CM-T1-SE improved with FS. CONCLUSIONS: STIR-T2
      TSE and FS-T1-SE with CM were most useful for MRI of carcinomas of the oral
      cavity and oropharynx.

PMID- 8527754
TI  - [The MRT of the orbit: the value of T1-weighted frequency-selective fat
      saturation at 1.0 and 1.5 tesla].
AB  - PURPOSE: To evaluate the diagnostic performance of fat suppression T1-weighted
      compared to conventional T1-weighted gadolinium-DTPA-(Gd-)enhanced spin echo
      sequences in orbital imaging. MATERIAL AND METHODS: 31 patients with pathologic
      conditions or clinically suspected pathology of the orbita were examined using
      conventional T1-weighted (TR 400-500 ms/TE 15 ms/AC 3) and fat suppression T1
      weighted (TR 370-500 ms/TE 15 ms/AC 3) spin echo-sequences before and after i.v.
      injection of 0.1 mmol/kg Gd-DTPA. All images were evaluated by three radiologists
      experienced in MR imaging, concerning anatomical and pathological structures as
      well as artifacts. The images were graded on a scale of 1-5 (5 = excellent to 1 =
      poor). RESULTS: The evaluation of anatomic structures showed that the fat
      suppression technique was superior to the conventional technique in respect of
      visualising the extraocular muscles (4.4 to 3.4, p < 0.05) and also with regard
      to the optic nerve (3.68 to 3.78). Pathological conditions of the orbit (optic
      glioma and neuritis, spread of local tumours to the orbit), however, were better
      visualised using the fat suppression technique (4.3 to 2.95, p < 0.05).
      CONCLUSION: Contrast-enhanced T1-weighted fat suppressed spin echo-sequences are
      useful in pathological conditions of the orbita. In optic neuritis they may be
      the only sequences to show the lesion.

PMID- 8527755
TI  - [Turbo-spin-echo sequences with selective fat suppression (SPIR) in the MRI of
      focal liver lesions at 0.5 tesla].
AB  - PURPOSE: The value of T2 weighted turbo-spin-echo sequences with selective fat
      suppression (TSE-SPIR) in the detection and differential diagnosis of focal liver
      lesions was compared to TSE sequences and conventional T1 weighted spin-echo (T1
      SE) sequences at 0.5T. METHODS: In 50 patients with focal liver lesions T1 SE-TSE
      , and TSE-SPIR sequences were performed. Two independent readers evaluated the
      sequences with regard to the image quality, fat suppression, and the number and
      conspicuity of liver lesions. Quantitative analysis was performed by tumour-liver
      contrast-to-noise (CNR) measurements. RESULTS: From a total of 118 liver lesions
      the T1 SE sequence, the TSE sequence, and the TSE-SPIR sequence showed 85.6%,
      83.9%, and 91.5%, respectively (p < 0.05). The tumour-liver CNR of malignant
      liver lesions was 30.2-46.6% higher on the TSE-SPIR sequence compared to the TSE
      sequence (p < 0.01). With the exception of fat-containing lesions there was no
      significant difference of CNR in benign lesions on both TSE sequences.
      CONCLUSION: With regard to lesion detection the TSE-SPIR sequence is superior to
      the TSE sequence without fat suppression, whereas it is inferior to the TSE
      sequence in the differential diagnosis of benign and malignant lesions.

PMID- 8527756
TI  - [Experiences with the endovascular embolization therapy of aneurysms of the
      splanchnic arteries--a report on 13 cases].
AB  - PURPOSE: The authors report on their experience in endovascular embolization
      therapy in 13 cases with splanchnic artery aneurysms or pseudoaneurysms. PATIENTS
      AND METHODS: Three patients suffered from true aneurysms, ten patients presented
      pseudoaneurysms of different origin. Eight patients were transferred to our
      department for life-threatening intestinal bleeding. Five patients showed
      transpapillary bleeding, four of whom presented with haemobilia and one patient
      had intermittent bleeding into the pancreatic duct due to a true aneurysm of the
      splenic artery. Embolization was performed using a coaxial microcatheter coil
      delivery system. In 4 patients the aneurysm-bearing vessel was temporarily
      blocked during the intervention. RESULTS: In 11 patients definite occlusion of
      the aneurysm was obtained without surgical intervention. In one patient,
      suffering from a splenic aneurysm, we observed a partial inadvertent embolisation
      of the spleen which did not require further treatment. In one case, rupture of an
      hepatic aneurysm during embolization occurred. One patient with pseudoaneurysm
      due to displacement of a port catheter showed severe rebleeding one day after
      embolisation. CONCLUSION: Transcatheter embolization is an effective method for
      treatment of aneurysms of the splanchnic arteries. To avoid life-threatening
      bleeding due to rupture of the aneurysm, the feeding vessel should be temporarily
      blocked during embolization therapy.

PMID- 8527757
TI  - [A modified technic for local rt-PA catheter-mediated lysis].
AB  - PURPOSE: To develop an economic and efficient concept for more time-saving local
      rt-PA thrombolysis therapy. METHOD: 40 patients with peripheral vascular
      occlusive disease stage IIb-III according to the Fontaine classification and with
      angiographically proven occluded segments of pelvic and lower limb arteries were
      treated by a modified concept of local rt-PA catheter thrombolysis. Via a thin
      guide wire the catheter for thrombolysis is slowly advanced through the thrombus
      without fluoroscopic control, outside the room in which angiography is performed.
      In 24 cases a short-term lysis and in 16 cases a long-term lysis was carried out.
      RESULTS: The initial success rate was 75%, the patency rate in six months' follow
      up was 66.7%. The ankle-brachial index decreased from 0.4 +/- 0.3 to 0.8 +/- 0.2
      on the average. There were no relevant clinical complications. The average
      occupancy time of the angiography room or table was 60 +/- 52 min, the average
      time of fluoroscopy was 17 +/- 13 min. CONCLUSION: In modified local rt-PA
      thrombolysis, short-term lysis and long-term lysis were mostly performed outside
      the angiography room, so that the exposure to radiation and there fore the
      radiation dose were reduced for both the patient and the attending staff. The
      angiography room is thus available for other patients and can therefore be used
      more efficiently.

PMID- 8527758
TI  - [The MRT of osteophytosis in experimental gonarthrosis].
AB  - PURPOSE: The value of MRI for the detection of knee osteophytosis was determined
      in an animal osteoarthritis model. METHODS: 10 dogs with experimentally induced
      unilateral osteoarthritis of the knee were investigated with MRI including 2-D
      spin echo (SE) and 3-D-gradient echo (GE) imaging. The results were correlated
      with gross and histopathologic findings and with radiography. RESULTS: Osteophyte
      formation appeared early in the osteoarthritic process. Pathological analysis
      yielded 65 osteophytes. With 3-D-GE imaging, 91% of the osteophytes were
      detected, while 68% were visible on 2-D-SE images. With two-level radiography,
      43% of the osteophytes were diagnosed. Additional use of tunnel view and
      conventional tomography increased the detection rate to 65%. Independent of the
      imaging technique, MRI revealed three different signal patterns of the osteophyte
      bone structure. Compared with the histologically evident fat marrow content and
      the grade of bone sclerosis, best agreement was achieved with 2-D-SE sequences.
      However, a discrepancy remained in 22%. A fibrocartilaginous layer at the
      osteophyte surface could be delineated especially on 3-D-GE images. CONCLUSIONS:
      MRI provides the highest standard in non-invasive diagnosis of osteophytes in the
      knee. 3-D-GE imaging in particular can demonstrate early and small osteophyte
      formation.

PMID- 8527759
TI  - [The diagnosis and fragmentation therapy of acute massive pulmonary embolism with
      a rotatable pigtail catheter: experimental studies].
AB  - PURPOSE: A dedicated pigtail catheter system which allows angiographic
      documentation and adjunctive mechanical fragmentation of pulmonary emboli was
      evaluated in an animal experiment. MATERIAL AND METHOD: The 5-F catheter provided
      with an oval side hole proximal to the pigtail tip was rotated manually or with
      an electric drive, and with the wire as a rotation axis. Pulmonary embolic
      occlusions were recanalized in ten dogs. Catheter positioning, monitoring,
      rotation behaviour, safety and fragmentation properties were assessed. RESULTS:
      The catheter system was rapidly positioned and easily monitored in the pulmonary
      arteries. On average, 55% (+/- 20%) of the embolic occlusions were recanalized.
      Embolus fragmentation reduced the emboli-induced increase of the pulmonary
      arterial mean pressure by 72%. In three dogs, histology revealed slight
      perivascular haemorrhage. CONCLUSION: Partial recanalisation of the pulmonary
      arteries was achieved rapidly with relative ease of instrumentation. Since
      fragmentation technique is an adjunct to the commonly performed pigtail
      catheterization of the pulmonary arteries, no special training is required.

PMID- 8527760
TI  - [Contrast agent retention in a jejunal diverticulum and small-intestine
      volvulus].

PMID- 8527761
TI  - [Fournier's gangrene in a woman in computed tomography].

PMID- 8527762
TI  - [The regression of a hepatocellular adenoma after the withdrawal of hormonal
      contraception].

PMID- 8527763
TI  - [Pseudarthrosis of the atlas after Jefferson's fracture].

PMID- 8527764
TI  - [Traumatic spinothoracic cerebrospinal fluid fistula].

PMID- 8527765
TI  - [Gadolinium-DTPA (Magnevist) as contrast medium for galactography].

PMID- 8527766
TI  - [Leukoencephalopathy under cisplatin therapy].

PMID- 8527767
TI  - [Morphofunctional features of parietal cells from a hibernating rodent in varying
      physiological states].

PMID- 8527768
TI  - [Ultrastructural changes of the interstitial cells in the kidney medulla during
      development of endotoxic shock].

PMID- 8527769
TI  - [Wenckebach arrhythmia, acquired after discharge stimulation of the cat vagus
      nerve].

PMID- 8527770
TI  - [Physiological concentration of endothelin-1 only causes expansion of coronary
      vessels in anesthetized rats].

PMID- 8527771
TI  - [The effect of superoxide dismutase on seizures in an experimental rat model of
      epilepsy].

PMID- 8527772
TI  - [Possibility of enzyme therapy for correction of metabolic disorders].

PMID- 8527773
TI  - [Changes in the coagulating and aggregating activity of alpha-thrombin by a
      synthetic analog of the thymosin fragment alpha 1(24-28)].

PMID- 8527774
TI  - [A comparative analysis of the polypeptide composition of heat shock proteins 70
      synthesized in Wistar and August rat myocardium].

PMID- 8527775
TI  - [Kinetics of blood leukocytes in mice with alloxan diabetes].

PMID- 8527776
TI  - [The role of cholinergic regulation of the heart in the protective antiarrhythmic
      effect of adaptation to continuous moderate stress].

PMID- 8527777
TI  - [The role of intra-osseal receptors in modulating afferent and motor reactions].

PMID- 8527778
TI  - [Adaptation to periodic hypoxia and diet with omega-3 polyunsaturated fatty acids
      increases the stability of myocardial sarcoplasmic reticulum Ca2+ transport to
      free radical oxidation].

PMID- 8527779
TI  - [Activation of nitric oxide formation mediated by metabotropic glutamate
      receptors in primary cultures of cerebellar granule cells].

PMID- 8527780
TI  - [Binding of aldosterone with rat brain corticosteroid receptors: effect of
      typological features of behavior and stress].

PMID- 8527781
TI  - [Endogenous phosphorylation of lysosomal proteins from rat heart and liver in the
      early post-resuscitation period].

PMID- 8527782
TI  - [Activity of NO-synthase and radical formation in rat brain sections: age
      dependence].

PMID- 8527783
TI  - [Sedative and antistress action of a peptide complex isolated from human amnion].

PMID- 8527784
TI  - [Genetic regulation of plasmid transfer].

PMID- 8527785
TI  - [Effect of low doses of piracetam on conditional reflex memory in rats].

PMID- 8527786
TI  - [Hemostatic properties of gaseous ozone].

PMID- 8527787
TI  - [The effect of parlodel on development of depressive syndrome in rats, caused by
      administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)].

PMID- 8527788
TI  - [The effect of fractionated introduction of an antigen on rosette formation in
      mice].

PMID- 8527789
TI  - [Dynamics of level of peritoneal exudate cellular elements in BALB/c mice
      infected with Coxsackie virus A13].

PMID- 8527790
TI  - [Age changes in alpha-1-adrenoreceptors in sections of brains from hypertensive
      NISAG rats: their possible role in development of arterial hypertension].

PMID- 8527791
TI  - [Expression of the human alpha-1-antitrypsin gene in transgenic rats].

PMID- 8527792
TI  - [The effect of oxypine on tissue edema in allergic rabbits].

PMID- 8527793
TI  - [The effect of season on lipid peroxidation indicators in the myocardium of
      animals with varying resistance to hypoxia].

PMID- 8527794
TI  - [Stereological analysis of absolute parameters of rat myocardium in contrasting
      temperatures].

PMID- 8527795
TI  - [Osteogenesis and angiogenesis in distraction osteosynthesis].

PMID- 8527796
TI  - [Ultrastructural reorganization of synaptic contacts in organotypic culture of
      the cerebral cortex in the presence of ethanol].

PMID- 8527797
TI  - Linkage and haplotype analysis of familial early-onset Alzheimer disease in
      Japanese population.
AB  - Linkage and haplotype analysis of eleven early-onset Alzheimer disease (AD)
      families was performed in relation to D21S210 and microsatellite DNA
      polymorphisms localized on chromosome 14q24.3. Linkage analysis of eight
      informative families out of eleven early-onset AD families disclosed the highest
      LOD score of 3.45 (theta = 0.00) at D14S77, while the locus of beta/A4 amyloid
      protein precursor gene was formally excluded within 10 cM from D21S210, given the
      evidence of recombinations in five families. Transmission disequilibrium study
      between the patients and controls without dementia indicated significant
      differences at D14S43 (p = 0.0001) and D14S71 (p = 0.02). Association study
      between genotypes linked or related to onset of AD and those of control also
      revealed a significant difference at D14S43 (p < 0.05), suggesting the existence
      of linkage disequilibrium. Moreover, the haplotypes at D14S43 linked with the
      onset of AD indicated a significant relationship with the mean age at onset.
      These results support that the major locus of early-onset familial AD is located
      on 14q24.3, and its close linkage to D14S43 and the existence of allelic
      heterogeneity were suggested.

PMID- 8527798
TI  - Cot-1 banding of human chromosomes using fluorescence in situ hybridization with
      Cy3 labeling.
AB  - We developed a new chromosome banding method by in situ hybridization of human
      Cot-1 DNA as a probe. Clear banding was produced on metaphase chromosomes of
      lymphoblastoid cells after probe detection with a fluorescent dye Cy3. Comparison
      with the known banding patterns revealed a similarity to the R-banding with some
      significant differences: some centromeric heterochromatin regions show Cot-1
      positive bands. This suggests that some repetitive sequences from the
      heterochromatin regions constitute a major component of Cot-1 DNA. This unique
      chromosome banding method, Cot-1 banding, may be used as a supplement to the
      conventional karyotype analysis. Scanning analysis of the fluorescence
      intensities of Cot-1 banding and Q-banding are useful for objectively analyzing
      the banding pattern including a detection of chromosome aberrations. The Cot-1
      banding with Cy3 is particularly powerful when applied for the gene mapping by
      fluorescence in situ hybridization (FISH) because red fluorescence of Cy3 for
      chromosome staining can be readily distinguished from green fluorescence of
      fluorescein isothiocyanate (FITC) for probe labeling. Using this novel method, we
      mapped a 4 kb-DNA fragment from myelin protein zero (MPZ) gene on the chromosome
      1q22 to q23.

PMID- 8527799
TI  - Three Japanese patients with Crigler-Najjar syndrome type I carry an identical
      nonsense mutation in the gene for UDP-glucuronosyltransferase.

PMID- 8527800
TI  - Familial pericentric inversion incidentally detected at prenatal diagnosis.
AB  - A case of familial heterozygous pericentric inversion of chromosome 1
      [inv(1)(p13q23)] is presented. The inversion was incidentally detected in a fetus
      whose mother received prenatal chromosomal diagnosis due to her age (40 years
      old), and thereafter the same inversion was detected in the father whose
      phenotype was normal. No abnormalities were found in the phenotype of the newborn
      carrier. Semen analysis of the father revealed normal findings. The couple had no
      history of spontaneous abortion.

PMID- 8527801
TI  - High incidence of a polymorphic variant of erythrocyte membrane protein, Band 3
      Memphis, on a western Japanese island.
AB  - Band 3 is the major membrane protein of erythrocytes, which binds membrane
      skeletal proteins, glycolytic enzymes, and hemoglobin and transports various
      kinds of anions. Band 3-Memphis is a variant of Band 3, the amino terminal
      fragment of which depicts a slow electrophoretic mobility on sodium dodecyl
      sulfate-polyacrylamide gel. The frequency of Band 3-Memphis varies among
      populations, with a higher frequency among the Japanese. We investigated the
      frequency of Band 3-Memphis in a western Japanese island which is relatively
      isolated from the main islands, finding that the frequency of Band 3-Memphis of
      the inhabitants of this island is significantly higher than the frequency of the
      Japanese based on the survey in Kyushu Island. This indicates that there may be
      differences of population in the frequency of Band 3-Memphis in Japan and that
      Band 3-Memphis may be a good marker to genetically differentiate each population.

PMID- 8527802
TI  - Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant
      retinitis pigmentosa.
AB  - Heterozygous missense mutation in codon 15 of the rhodopsin gene was detected in
      a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition
      of adenine to guanine at the second nucleotide in codon 15 (AAT-->AGT),
      corresponding to a substitution of serine residue for asparagine residue (Asn-15
      Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal
      recessive RP (ARRP) and 34 normal individuals had this alteration. Her
      funduscopic findings were sectorial in type similar to that of the patients with
      the same mutation found in an Australian pedigree (Sullivan et al., 1993). This
      study shows phenotypic similarities in patients with the same mutation of a
      different ancestry.

PMID- 8527803
TI  - Detection of MspI RFLP in human THY1 gene by the polymerase chain reaction.
AB  - THY1 gene encodes a cell surface glycoprotein predominantly expressed in brain
      and peripheral nerves. Human THY1 gene region on chromosome 11q23 has been
      implicated in susceptibility to type 1 diabetes (Wong et al., 1991). Two primers
      derived from the sequences flanking the polymorphic MspI site in intron 2 of the
      human THY1 gene (Gatti et al., 1988) were selected for RCP to amplify a 566 bp
      fragment that spans the MspI polymorphism. Polymorphism was detected by MspI
      digestion of the PCR product.

PMID- 8527804
TI  - Two dinucleotide repeat polymorphisms at the D8S1442 and D8S1443 loci.

PMID- 8527805
TI  - Three dinucleotide repeat polymorphisms at the D8S1217, D8S1220, and D8S1221
      loci.

PMID- 8527806
TI  - A highly polymorphic dinucleotide repeat at the D8S1222 locus.

PMID- 8527807
TI  - Distribution and pharmacology of alpha 2-adrenoceptors in the central nervous
      system.
AB  - Three subtypes of the alpha 2-adrenoceptor have been characterized. The drugs
      currently available which most specifically activate (e.g. dexmedetomidine) or
      antagonize alpha 2-receptors (e.g. atipamezole, idazoxan) do not show significant
      differences in their affinities for the subtypes. The drugs which do show some
      subtype selectivity (oxymetazoline for alpha 2A; prazosin for alpha 2B and alpha
      2C) are not useful for in vivo pharmacology due to their relative nonspecificity
      in binding to other receptors (e.g. alpha 1-adrenoceptors). By examining the
      distribution of the mRNA coding for the three subtypes, it has been possible to
      map those regions in the brain which possess cells which synthetize the distinct
      subtypes. The mRNA coding for alpha 2A receptors is found throughout the brain,
      especially in locus coeruleus, a region which contains the cell bodies for the
      ascending and descending noradrenergic neurones. The mRNA for alpha 2B receptors
      was only found in thalamus. The alpha 2C mRNA had a wider distribution, in basal
      ganglia its expression was particularly intense. One must hope that the fact that
      the receptor subtypes are not uniformly distributed throughout the brain means
      that new subtype selective drugs will not suffer from the same broad diversity of
      actions of the present alpha 2-agonists and antagonists.

PMID- 8527808
TI  - Bulbospinal catecholamine neurones and sympathetic pattern generation.
AB  - Populations of neurones containing noradrenaline, dopamine and possibly
      adrenaline project to the spinal cord where they innervate sympathetic
      preganglionic neurones (SPN). Studies are described which illustrate the actions
      of catecholamines on SPN and which suggest ways in which the catecholamine
      neurones could regulate the cardiovascular system. Experiments on rats using,
      intrathecal application of drugs to the spinal cord, iontophoresis, or
      superfusion of drugs whilst recording either postganglionic nerve activity,
      extracellularly or intracellularly from SPN respectively, reveal that
      catecholamines may excite or inhibit SPN. A slow depolarisation is mediated by
      alpha 1 adrenoceptors whereas alpha 2 adrenoceptors mediate a slow
      hyperpolarisation. Catecholamines may also excite glycinergic interneurones which
      elicit fast IPSPs in SPN. By regulating different ionic conductances in the
      membrane of SPN catecholamines are able to induce SPN to discharge tonically or
      to oscillate with bursts of action potentials. Furthermore these actions may be
      modified in the presence of an excitatory amino acid. It is suggested that via
      these mechanisms differential responses in the sympathetic outflow could be
      produced.

PMID- 8527809
TI  - Mechanisms of catecholamine secretion from adrenal chromaffin cells.
AB  - Adrenaline and noradrenaline are released from adrenal medullary chromaffin cells
      by regulated exocytosis from stored secretory granules. Many aspects of the
      mechanisms by which exocytosis is activated in chromaffin cells are now
      understood in detail and these cells have provided an important model for the
      study of neuroendocrine secretion in general. Exocytosis is triggered by Ca2+
      influx which activates a multistep process involving at least two Ca(2+)-binding
      proteins with distinct Ca2+ affinities. Several cytosolic and membrane proteins
      have been implicated by functional studies as components of the exocytotic
      machinery. The likely roles of these proteins in exocytosis are discussed in this
      review and the questions that remain for the understanding of the molecular basis
      of catecholamine release are highlighted.

PMID- 8527810
TI  - Pheochromocytoma--the catecholamine dependent hypertension.
AB  - Pheochromocytoma is a unique type of hypertension caused by excessive production
      of catecholamines by the chromaffin tumor. Pheochromocytoma, a potentially life
      threatening disease, is a rare cause of hypertension. The incidence varies from
      0.1 to 0.8% of hypertensive population. The author's experience is based on 138
      patients treated in one institution from 1956 to 1995. Hormonal activity of
      pheochromocytoma varies considerably, influencing the pattern, of blood pressure
      and the clinical symptoms. It is emphasized that different other humoral
      mechanisms may play a role in the pathophysiology of this type of endocrine
      hypertension. Biochemical tests and non-invasive localizing methods are essential
      for the definite diagnosis of pheochromocytoma. A great progress has been made in
      this respect during the last three decades. Surgical removal of the tumor is the
      only definite therapy with low morbidity and mortality.

PMID- 8527811
TI  - Adrenergic regulation of the hypothalamic-pituitary-adrenal axis under basal and
      social stress conditions.
AB  - The significance of adrenergic neurons and anterior pituitary and hypothalamic
      adrenergic receptors in stimulation of the hypothalamic-pituitary-adrenal (HPA)
      axis by corticotropin releasing hormone (CRH) and vasopressin (AVP) was
      investigated under basal conditions and after three-days crowding stress in
      conscious rats. In nonstressed rats the corticosterone response to phenylephrine,
      an alpha 1-adrenergic receptor agonist, was totally abolished or considerably
      reduced by prazosin, an alpha 1-receptor antagonist, when both those drugs were
      given ip or icv, respectively. The corticosterone response to ip isoproterenol, a
      beta-adrenergic agonist, was abolished by icv or ip pretreatment with
      propranolol, a beta-adrenergic receptor antagonist. These results indicate
      involvement of functional alpha 1-adrenoceptors in the hypothalamus and anterior
      pituitary corticotrops and pituitary beta-adrenoceptors in stimulation of the HPA
      axis. AVP given ip was almost as potent as CRH in stimulating corticosterone
      secretion. The stimulatory effect of AVP given ip or icv on corticosterone
      secretion was significantly diminished by propranolol, but not prazosin or
      yohimbine, indicating an involvement of beta-adrenergic receptors. The specific
      noradrenergic neurotoxin DSP-4, given ip 11 days before the experiment,
      considerably diminished the hypothalamic noradrenaline (NA) level but did not
      influence the resting and icv CRH- or AVP-stimulated corticosterone secretion. In
      nonstressed rats CRH further enhanced significantly the DSP-4-elicited fall in
      hypothalamic NA, whereas AVP almost totally prevented that decrease. In stressed
      rats CRH considerably antagonized the DSP-4-induced decrease in the hypothalamic
      NA level while AVP did not affect that decrease. The CRH- and AVP-elicited
      changes in hypothalamic NA were not correlated with changes in corticosterone
      secretion. Tree-day crowding stress did not affect the CRH-induced corticosterone
      secretion, whereas it considerably reduced the AVP-evoked corticosterone
      response. These results indicate that pituitary and hypothalamic adrenergic
      receptors are significantly involved in the AVP- and CRH-induced HPA axis
      stimulation, but the hypothalamic NA level, though modified by these peptides,
      does not significantly influence the HPA response.

PMID- 8527812
TI  - Influence of the central histaminergic systems on the pituitary-adrenocortical
      response to met-enkephalinamide.
AB  - A possible involvement of hypothalamic histamine and histamine receptors in the
      hypothalamic-pituitary-adrenocortical (HPA) activity stimulated by Met
      enkephalinamide (DADM) was investigated indirectly by corticosterone secretion in
      conscious rats. DADM, a delta-opioid receptor agonist, given
      intracerebroventricularly (i.v.c.) induced a significant increase in the serum
      corticosterone level, which was considerably reduced by ip or icv pretreatment
      with naltrexone, an opioid antagonist. Pretreatment with alpha
      fluoromethylhistidine (alpha-FMH) 20 mg/kg ip or 50 micrograms icv, an inhibitor
      of the brain histamine synthesis, drastically reduced the hypothalamic histamine
      level, did not affect the levels of noradrenaline and dopamine, and almost
      abolished the DADM-induced corticosterone response. Mepyramine and cimetidine,
      histamine H1- and H2-receptor antagonists, did not substantially change the
      corticosterone response to DADM. The present results suggest that DADM stimulates
      the HPA activity via central delta-opioid receptors. They also indicate that the
      reduction of the HPA response to DADM by alpha-FMH is connected with significant
      diminution of hypothalamic histamine, but not noradrenaline or dopamine levels.
      Central histamine receptors do not mediate the metenkephalinamide-induced HPA
      stimulation.

PMID- 8527813
TI  - Reactivity of isolated human right atria to norepinephrine in various disease
      states.
AB  - The reactivity of isolated, electrically driven, right human atrial muscle to
      norepinephrine was studied in patients with coronary heart disease, with and
      without proximal right coronary artery occlusion, and in patients with mitral
      valve disease. The dose-effect curves for norepinephrine and ED50 doses for each
      group were compared. We found no difference in reactivity of atria from both
      coronary artery disease groups. The mitral valve disease group dose-effect curve
      was shifted to the right (potency ratio 3.98), and the maximal effect was
      significantly higher than in both coronary artery disease groups. We suggest that
      adrenoreceptor down regulation could account for observed ED50 difference. The
      difference in maximal responses could depend on more effective contraction
      mechanism in mitral valve disease myocardium. We conclude that occlusion of
      proximal right coronary artery does not necessarily mean ischaemia of right
      atrium and/or ischaemia does not change myocardium reactivity to norepinephrine.

PMID- 8527814
TI  - The effect of oxytocin on hCG action in phosphoinositide turnover in porcine
      myometrial smooth muscle cells.
AB  - The aim of this study was to investigate the effects of hCG, hCG plus oxytocin
      and oxytocin on [3H] inositol phosphate (IP) formations in porcine myometrial
      cells obtained from ovariectomized and cyclic gilts. Myometrial cells were
      treated with radioactive myo-[3H]inositol for 48 hours, washed and pre-incubated
      with 10 mM LiCl, and then different doses of hCG (10, 100, 1000 mU) were added
      over 24 h. At the end of the last day of culture some wells were treated with 1
      microM oxytocin for 30 min. The highest production of total inositol phosphates
      (d.p.m.) was found in cells from ovariectomized gilts given in vivo estradiol
      benzoate and progesterone for five consecutive days and treated with 1000 mU hCG
      and 100 mU hCG plus 1 microM oxytocin (984 +/- 84 and 1063 +/- 131 vs 314 +/- 36,
      respectively). There was also a very significant increase of IP1 after the
      addition of 1000 mU hCG (p < 0.001) and IP1 and IP3 when 1000 mU hCG plus
      oxytocin were added (p < 0.001 and p < 0.01, respectively). Myometrial cells
      harvested from ovariectomized, untreated in vivo, gilts did not respond to both
      oxytocin and hCG in vitro. Only oxytocin alone increased the formation of IPs in
      cells from ovariectomized pigs treated with estradiol in vivo (p < 0.01).
      Myometrial cells obtained from cyclic pigs during the luteal and follicular
      phases of the estrous cycle responded to lower doses of hCG (10 mU), causing
      significant production of IPs (p < 0.05). The highest dose of hCG plus oxytocin
      provoked accumulation of total [3H]inositol phosphate (p < 0.05) 53% over the
      basal level on days 21/1 of the estrous cycle. The present study demonstrates
      that hCG and oxytocin can increase the accumulation of inositol phosphates in
      porcine myometrial cells. However, this formation is dependent on the steroid
      hormone status of animals.

PMID- 8527815
TI  - Effect of hypothermia on the insulin-receptor interaction in adipose plasma
      membranes.
AB  - The aim of the study was to compare the number and affinity of insulin receptors
      in adipose tissue of both normothermic and hypothermic rats. Plasma membranes
      from epididymal adipose tissue were prepared and purified according to Havrankowa
      and binding assay was performed using (125I)-iodoinsulin. The kinetic parameters
      of the hormone-receptor interaction were analysed by the method of Scatchard
      using the LIGAND--Pc v.3.1. computer program of Munson and Rodbard. The binding
      potency of insulin was calculated as IC50 using the ALLFIT--Pc v. 2.7. computer
      program. Maximum specific insulin binding to plasma membranes in adipose tissue
      was decreased in the hypothermic rats but half-maximum displacement of tracer
      insulin was similar in the normothermic and hypothermic group suggesting that
      reduced receptor numbers rather than reduced affinity accounted for the
      difference.

PMID- 8527816
TI  - The role of capsaicin-sensitive sensory neurons and nitric oxide in regulation of
      gastric mucosal growth.
AB  - Capsaicin and nitric oxide (NO) cause potent vasorelaxation which is important in
      gastroprotective activity against damage but the mechanisms underlying these
      effects have not been elucidated. This study investigated the influence of
      capsaicin-induced functional ablation of afferent neurons and inhibition of NO
      production on the gastric mucosal growth in normal conditions, after 48 h fasting
      and subsequent refeeding. We found that ablation of sensory neurons by capsaicin
      pretreatment (100 mg/kg over 3 days) reduced by around 45% the mucosal blood flow
      (MBF), as measured by laser Doppler flowmetry, in normal fed and refed rats,
      while by 15% only in fasted animals. This last group of animals had significant
      decrease in the MBF even in control conditions as compared to that recorded in
      fed animals. This drop in MBF after capsaicin-induced denervation was accompanied
      by a significant decrease in DNA synthesis (by 40% in control group and 35% in
      refed rats) and was less pronounced in the group of fasted rats (23%). Ablation
      of sensory neurons resulted in the decrease in the stomach weight and RNA content
      in regular feed and refed but not in 48 h fasted group of animals. Treatment with
      NG-nitro-L-arginine (L-NNA; 2 x 20 mg/kg daily s.c.), a selective blocker of NO
      synthase, significantly suppressed the MBF in all three groups of animals tested
      but this suppression was less pronounced when compared to capsaicin pretreatment.
      This inhibitory effect of L-NNA on MBF was fully antagonized by L-arginine (2 x
      100 mg/kg daily s.c.). L-NNA injection s.c. reduced the DNA synthesis (36%
      control group, 38% refed animals, 18% fasted rats), stomach weight, RNA and DNA
      content in all tested groups of rats. This inhibition was reversed by the
      addition of L-arginine. The combination of capsaicin and L-NNA decreased the MBF
      significantly and the inhibition was stronger than the effect of each substance
      given alone. In normal fed and refed rats, the neurotoxic dose of capsaicin
      together with L-NNA significantly decreased the DNA synthesis, stomach weight,
      RNA and DNA content but these effects were smaller than the sum of the effects of
      each agent given alone. We conclude that both the capsaicin-induced denervation
      and the suppression of endogenous NO by L-NNA inhibit the growth of the gastric
      mucosa by the mechanism involving, at least in part, the suppression of gastric
      mucosal blood flow.

PMID- 8527817
TI  - Determination of aflatoxins in dust and urine by liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - A liquid chromatography/electrospray ionization tandem mass spectrometry method
      is described for the determination of aflatoxins B1, B2, G1 and G2. Samples of
      naturally contaminated airborne dust and spiked urine were cleaned up on
      immunoaffinity columns and analysed by liquid chromatography using either mass
      spectrometry detection or post-column derivatization with bromine and
      fluorescence detection. With tandem mass spectrometry, detection limits (S/N = 3)
      calculated as amount ejected on column were: aflatoxin B1 4 pg, B2 4 pg, G1 5 pg,
      and G2 10 pg.

PMID- 8527818
TI  - A simple method for differentiating Leu and Ile in peptides. The negative-ion
      mass spectra of [M-H]- ions of phenylthiohydantoin Leu and Ile.
AB  - Phenylthiohydantoin (PTH) amino acid derivatives are formed during sequential
      Edman degradation of peptides and proteins. Isomeric Leu and Ile (which differ
      only in respectively having iso-butyl and sec-butyl chains, and are often
      difficult to distinguish by conventional mass spectrometric techniques) may be
      readily identified by the characteristic decompositions of the [M-H]- ions of
      their PTH derivatives. The Leu spectrum shows major loss of propane, while that
      of the Ile derivative shows elimination of both methane and ethane. This method
      may be used routinely with 10 microgram quantities of peptide material.

PMID- 8527819
TI  - Collision-induced dissociation of multiply charged peptides in an ion-trap
      storage/reflectron time-of-flight mass spectrometer.
AB  - Single-frequency collisional activation of multiply charged peptides has been
      studied via electrospray ionization in an ion trap storage/reflectron time-of
      flight device (IT/reTOF). Several peptides with molecular weights ranging from
      600 to 1700 were used to demonstrate that sequence information can be obtained
      with this hybrid instrument with a sensitivity in the low picomole level.
      Further, a resolution of nearly 1000 can be obtained for the fragment products,
      due to the cooling effects of the buffer gas in the trap before analysis by the
      reTOF. The influence of the primary structure of the peptides on the observed
      collision-induced fragmentation patterns is discussed. Although the current study
      is limited by the electronics, in terms of its ion isolation capabilities, it is
      demonstrated that the device has the potential for obtaining sequence information
      for peptides with excellent sensitivity and relatively high resolution.

PMID- 8527820
TI  - Quantification of 7-dehydrocholesterol in plasma and amniotic fluid by liquid
      chromatography/particle beam-mass spectrometry as a biochemical diagnostic marker
      for the Smith-Lemli-Opitz syndrome.
AB  - The qualitative and quantitative determination of cholesterol and 7
      dehydrocholesterol (7-DHC) in plasma as a biochemical diagnostic marker for the
      Smith-Lemli-Opitz syndrome by liquid chromatography/particle beam interface-mass
      spectrometry (LC/PB-MS) is presented. Baseline separation of cholesterol and 7
      DHC is achieved on a silica column with hexane+ethanol (99: 1 v/v) as mobile
      phase within a 10 min analysis. Recoveries of cholesterol and 7-DHC in a simple
      two-phase extraction system are nearly 100%. The absolute limit of detection
      using LC/PB-MS is approximately 10 ng. The method presented allows extraction,
      analysis and quantification of cholesterol and 7-DHC within 15 min without the
      necessity of sample derivatization.

PMID- 8527821
TI  - Analysis of tilmicosin in swine liver extracts by liquid
      chromatography/atmospheric pressure chemical ionization mass spectrometry.
AB  - Tilmicosin is a semisynthetic macrolide antibiotic used in the treatment of
      respiratory disease in cattle and swine. The technique of liquid
      chromatography/atmospheric pressure chemical ionization mass spectrometry
      (LC/APCI-MS) was employed in an on-line capacity for the analysis of tilmicosin
      in extracts from spiked swine liver. Increasing the potential in the cone/skimmer
      region of the ion source resulted in an increased abundance of unique
      structurally indicating fragment ions of tilmicosin. Three ions, [M+H]+ and two
      diagnostic fragment ions were chosen for confirmation of the presence of
      tilmicosin in swine liver tissue extracts using the mass spectrometer in selected
      ion monitoring mode. The ion abundance ratios arising from any given combination
      of ions in data acquired from extracts of swine liver tissue spiked with
      tilmicosin at 5 and 10 ppm were within +/- 10% of the corresponding mean standard
      abundance ratio, and duplicate sample analyses exhibited < 10% relative standard
      deviation. These results suggest the potential for the application of LC/APCI-MS
      as a confirmatory technique for tilmicosin in swine liver.

PMID- 8527822
TI  - Revisit of MALDI for small proteins.
AB  - Matrix-assisted laser desorption/ionization (MALDI) was used for several small
      proteins (such as insulin) and for peptides. It was found that the detection
      efficiencies of MALDI for the insulin B chain and the insulin A chain are
      drastically different. Similar phenomena were also observed for various types of
      peptides. The positive-ion signal of MALDI in detecting proteins or peptides was
      found to be greatly enhanced by the presence of a basic amino acid in their
      chains. The experimental results indicate that this enhancement may arise from
      proton transfer in solution by an acid-base reaction between the protein/peptide
      and matrix molecule. This pre-protonated mechanism provides a low energy barrier
      for the ionization of peptides in a MALDI process, and greatly reduces the energy
      threshold of MALDI. Matrix effects on the ionization mechanism are discussed.

PMID- 8527823
TI  - Massive cluster ablation as preparation for organic secondary ion imaging.
AB  - A focused Cs+ beam was used to obtain secondary ion mass spectra and images from
      samples of stearic acid on gold before and after ablation by a beam of massive
      cluster ions. Ablation appears to have two effects on secondary ion emission.
      First, the number and intensity of peaks reflecting contamination are
      substantially reduced. Secondly, the absolute intensity of secondary ion current
      characteristic of the analyte increases. These features simplify mass spectra and
      improve contrast in the images obtained.

PMID- 8527824
TI  - Capillary zone electrophoresis/mass spectrometry: analytical need or an option?

PMID- 8527825
TI  - Molecular characterization of a common binding site for small molecules within
      the transmembrane domain of G-protein coupled receptors.
AB  - The cloning of over 100 members of the superfamily of G-protein coupled receptors
      has resulted in the identification and characterization of novel targets for
      therapeutic intervention. In addition, mutagenesis studies aimed at understanding
      the nature of the molecular interactions of these receptors with peptides and
      small molecules have led to advancements in the ability to synthesize novel
      therapeutic agents with high affinity and specificity for these receptors. These
      experiments have shown that there is a common binding site for small molecules
      within the transmembrane domain of G-protein coupled receptors regardless of the
      nature of the endogenous, physiologically relevant receptor agonist. Finally, the
      demonstration that the binding sites for peptide agonists and nonpeptide
      competitive antagonists are not necessarily identical has provided insights
      regarding the mechanism of competitive antagonism in these receptors.

PMID- 8527826
TI  - Toxic effects of anabolic-androgenic steroids in primary rat hepatic cell
      cultures.
AB  - Hepatic complications in athletes and bodybuilders after abusing anabolic
      androgenic steroids (AAS) have been reported. Hepatic injury, including
      cholestasis, peliosis hepatis, hyperplasia, and tumors, have been attributed to
      abuse of the 17 alpha-alkylated AAS. Some of these pathological conditions have
      been reversed when individuals were converted to nonalkylated AAS regimens. The
      purpose of this study was to determine and compare the direct toxic effects of
      commonly abused AAS (both 17 alpha-alkylated and nonalkylated) in primary hepatic
      cell cultures. Primary cultures, established from 60-day-old Sprague-Dawley rats,
      were exposed to doses of 1 x 10(-8), 1 x 10(-6), and 1 x 10(-4)M 19
      nortestosterone, fluoxymesterone, testosterone cypionate, stanozolol, danazol,
      oxymetholone, testosterone, estradiol, and methyltestosterone for 1, 4, and 24
      hr. Lactate dehydrogenase (LDH) release, neutral red (NR) retention, and
      glutathione (GSH) depletion were evaluated to determine plasma membrane damage,
      cell viability, and possible oxidative injury, respectively. Those cultures
      exposed to the 17 alpha-alkylated AAS, methyltestosterone and stanozolol, at
      doses of 1 x 10(-4) M for 24 hr and the 17 alpha-alkylated AAS, oxymetholone, at
      1 x 10(-4) M for 4 and 24 hr showed significant increased in LDH release and
      decreases in NR retention while there were no significant differences with the
      nonalkylated steroids (testosterone cypionate, 19-nortestosterone, testosterone,
      and estradiol). GSH depletion was evaluated in cultures treated with 1 x 10(-8),
      1 x 10(-6), and 1 x 10(-4) M concentrations of methyltestosterone, stanozolol,
      and oxymetholone for 1, 2, 4, and 6 hr. Cultures exposed to 1 x 10(-4) M
      oxymetholone were significantly depleted of GSH at 2, 4, and 6 hr; cultures
      exposed to 1 x 10(-4) M methyltestosterone were significantly depleted of GSH at
      4 and 6 hr; and cultures exposed to stanozolol were not significantly depleted of
      GSH at any of the time periods tested. These data indicate that the 17 alpha
      alkylated steroids (methyltestosterone, oxymetholone, and stanozolol) are
      directly toxic to hepatocytes, whereas the nonalkylated steroids (testosterone
      cypionate, 19-nortestosterone, testosterone, and estradiol) show no effects at
      similar doses. These data demonstrate a trend toward a structural-activity
      relationship to AAS-induced toxicity in primary cultures of rat hepatocytes.

PMID- 8527827
TI  - Quantitative estimation of potentiation and antagonism by dose ratios corrected
      for slopes of dose-response curves deviating from one.
AB  - A shift of dose-response curves of a receptor agonist A by a receptor antagonist
      B to the right is frequently expressed or quantitated by calculating the dose
      ratio (DR) from the ED50 values obtained in the absence and presence of B. A
      comparison of ED50 values or a DR is also used in a more general way to express
      the effects of other antagonists or of potentiators. For this situation, where B
      is not competing with A for a binding site, slope-values may often deviate from
      one. Because the slope of shifted dose-response curves (deviating from one)
      affects the magnitude of enhancement or diminution at a given DR, we have to take
      it into account. For example, the same changes in effects are associated with DR
      = 10 at curves with slope = 1, but with DR = 2.15 in case of slope = 3.
      Enhancement and diminution expressed by dose ratios is more or less
      underestimated in case of curves with slope > 1. We therefore propose to
      quantitate potentiation and antagonism by a corrected DR (DRcorr), which can
      simply be calculated from the uncorrected DR at a given slope. Consequently, a
      DRcorr reflects a true measure of enhancement or diminution for curves with slope
      = 1, equivalent to that which would have been observed for curves with slope = 1.
      The practical value of this modification is exemplified and illustrated by
      analysis of experimental data.

PMID- 8527828
TI  - The effect of bile duct manipulation and pair-feeding on peripheral vascular
      neuroeffector mechanisms: in vitro studies.
AB  - Investigators studying the pathophysiological sequelae of bile duct ligation use
      different species of laboratory animals at varying postoperative times. There is
      also considerable variation in the type of control animal used for these
      experiments. In this study, we have attempted to validate our choice of the 3-day
      bile-duct-manipulated rat as the most appropriate control to study peripheral
      vascular neuroeffector mechanisms in bile-duct-ligated rats. We have compared the
      in vitro contractile response to norepinephrine in the absence and presence of
      cocaine, and the accumulation of the amine using 3H-norepinephrine of arterial
      rings and portal veins prepared from three different types of control rats-
      unoperated control, the 3-day bile-duct-manipulated and the 3-day pair-fed, bile
      duct-manipulated rats. In vitro arterial reactivity to norepinephrine in the sham
      operated rats was significantly attenuated and was associated with a cocaine
      sensitive increase in norepinephrine uptake. Portal veins from the same animals
      showed no changes in in vitro reactivity to norepinephrine, although bile-duct
      manipulation and pair-feeding enhanced amine uptake. This study has demonstrated
      that bile-duct manipulation and pair-feeding attenuate in vitro vascular
      reactivity and enhance norepinephrine uptake. These in vitro changes are more
      pronounced in arterial tissue than venous tissue. In conclusion, these data
      indicate that bile-duct manipulation is the control of choice when measuring in
      vitro vascular neuroeffector mechanisms in 3-day bile-duct-ligated rats.
      Furthermore, these data emphasize the need to validate the control when
      experiments involving bile-duct ligation are undertaken.

PMID- 8527829
TI  - Impact of cocaine on human placental function using an in vitro perfusion system.
AB  - The transport of cocaine from the maternal to fetal circulation and the effect of
      cocaine on placental function was investigated in vitro using dually perfused
      term human placentae with recirculation of both maternal and fetal perfusates. In
      the first experimental group (n = 5, 2 hr), after addition of 3H-cocaine and 14C
      inulin to the maternal circulation, steady state concentrations were achieved
      within 20 min on the maternal side. However, in the following 100 min, uptake of
      3H-cocaine remained higher than of the 14C-inulin on the maternal side. 3H
      Cocaine was transported more rapidly than 14C-inulin into the fetal circulation
      and was detected within 10-15 min of initiation of perfusion. In the second
      experimental group (n = 6), the maternofetal permeability of 14C-insulin was
      determined in the same placental perfusion in both the absence (control period, 2
      hr) and presence of cocaine (test phase, 2 hr) with its 3H-tracer. After the
      addition of cocaine (2-3 mg/L), the transfer of 14C-inulin was reduced from 6.59
      to 3.64 mL/gm per min (p < .001), indicating that cocaine alters placental
      permeability. In addition to its effect on placental permeability, cocaine
      decreases the rate of release of hCG into the maternal circulation--reduced from
      3.11 (control period) to 1.62 IU/min (test phase, p < .01).

PMID- 8527830
TI  - A simple, automatic method for morphometric analysis of the left ventricle in
      rats with myocardial infarction.
AB  - Induction of acute myocardial infarction in the rat is an established model for
      studying effects of therapeutic interventions. Images of sections of the rat left
      ventricle, stained with nitroblue tetrazolium, were digitized and several
      parameters estimated by dedicated software on an image analyzer (IBAS 2.0). The
      method was tested on 7 rats with 48-hr-old myocardial infarction and 4 sham
      operated controls. Infarct size can be evaluated by two largely used methods,
      based on area or on angular extension of the lesion. Results of the two methods
      are linearly correlated, but area calculations give values half of those obtained
      from angular extension. Five minutes were needed for a complete evaluation of a
      section of the left ventricle. Estimates of the parameters showed a relatively
      low between- and within-operator variability and a good correlation with a
      classic, but time-consuming, planimetric method. The method simultaneously
      measures infarct size and left ventricular geometry in the rat. The advantages
      over previous nonautomatic methods are simplicity, good reproducibility, and
      speed of execution, which make it particularly useful in the evaluation of drug
      effects.

PMID- 8527831
TI  - A rabbit tooth-pulp assay to quantify efficacy and duration of antinociception by
      local anesthetics infiltrated into maxillary tissues.
AB  - The rabbit tooth-pulp assay is well established as a method for measuring the
      efficacy and potency of parenteral analgesic drugs. We describe a method for
      administration of local anesthetic drugs into the maxillary arch and subsequent
      measurements of antinociceptive action. It was possible to use two different
      methods of ED50 estimation and to provide measures of the potency, efficacy, and
      duration of local anesthetic drugs. These measurements corresponded with in vitro
      estimates of potency and duration and with intrinsic observations of the clinical
      actions.

PMID- 8527832
TI  - Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene
      sulfonic acid.
AB  - Hapten-induced colitis is a widely used model for the study of the intestinal
      inflammation and for the testing of novel therapies. However, the hapten utilized
      in this model, trinitrobenzene sulfonic acid, is difficult to obtain in some
      countries. We therefore compared this hapten to two structurally related haptens
      to determine if they could be substituted for trinitrobenzene sulfonic acid in
      terms of inducing chronic colitis in the rat. Rats received one of the three
      haptens intracolonically, and the severity of colonic inflammation was assessed 3
      and 14 days later. Dinitrobenzene sulfonic acid produced colonic inflammation and
      ulceration that was indistinguishable from that induced by trinitrobenzene
      sulfonic acid at both time points. On the other hand, dinitrochlorobenzene
      produced acute colitis (3 days postadministration), but by Day 14 this
      inflammation had subsided. Dinitrobenzene sulfonic acid and trinitrobenzene
      sulfonic acid produced comparable levels of granulocyte infiltration into the
      colon (as measured by tissue myeloperoxidase activity and histology) at both time
      points. These studies suggest that for studies of up to at least 2 weeks in
      duration, dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produce
      comparable levels of colonic inflammation. Dinitrobenzene sulfonic acid therefore
      offers a useful and less expensive alternative to trinitrobenzene sulfonic acid.

PMID- 8527833
TI  - Solid-phase combinatorial chemistry and novel tagging methods for identifying
      leads.
AB  - Encoded combinatorial chemical synthesis on solid phase is a new paradigm in
      organic chemistry that provides chemists with powers similar to those enjoyed by
      molecular biologists. Encoded chemical libraries will have a profound impact on
      all endeavors that seek to identify molecules with optimized properties and to
      understand the factors governing molecular interactions. In particular, the
      discovery and optimization of new therapeutic and diagnostic drug molecules,
      traditionally a slow manual process, will be greatly accelerated by this
      technology.

PMID- 8527834
TI  - Update on computer-aided drug design.
AB  - Recent advances in computational methods for drug design include developments in
      quantitative structure-activity relationship approaches as well as novel
      structure-based strategies. Many new protein structures of pharmaceutical
      interest have been solved, a number of which contain a bound inhibitor. Continued
      progress has been reported in algorithms for de novo design, ligand docking, and
      scoring of protein-ligand binding energy. Meanwhile, several drugs that were
      designed by intensive use of computational methods are advancing through clinical
      trials.

PMID- 8527835
TI  - Docking small-molecule ligands into active sites.
AB  - Docking involves the development of computer algorithms that evaluate the binding
      modes of putative ligands in receptor sites. The principal advances of the past
      year have been the development of new algorithmic approaches, several of which
      incorporate conformational flexibility, and the increased use of docking to
      identify leads in drug-discovery programmes.

PMID- 8527836
TI  - Inhibitors of serine/threonine kinases.
AB  - Several serine/threonine kinase inhibitors have been described recently that are
      sufficiently selective, and therefore useful as biochemical probes, for studying
      the role of kinases in signaling pathways. In addition, these newer classes of
      kinase inhibitor may well provide an impetus for the development of drugs to
      attenuate certain cellular responses in the treatment of diseases. Importantly,
      within the past year, specific and potent inhibitiors have been reported for both
      the new mitogen-activated protein (MAP) kinase homolog CSBP and MAP kinase kinase
      1.

PMID- 8527837
TI  - Inhibitors of protein tyrosine kinases.
AB  - The description in the past year of several novel protein tyrosine kinase
      inhibitors, which exhibit dramatic improvements in potency and specificity over
      earlier agents, will be considered a major turning point in the field. These
      compounds appear to have the necessary pharmacological properties to finally
      allow clarification of whether suppression of specific tyrosine kinases is of
      therapeutic benefit in certain disease states.

PMID- 8527838
TI  - The Rac and Rho pathways as a source of drug targets for Ras-mediated
      malignancies.
AB  - The small GTP-binding proteins Rac and Rho are key control elements in the
      reorganization of the actin cytoskeleton induced by growth factors or oncogenic
      Ras. It has been established recently that Rac and Rho also play a crucial role
      in Ras transformation. This suggests that the elements in the pathways regulated
      by Rac and Rho are valid targets for cancer therapy. Several important components
      of those signaling pathways have now have identified.

PMID- 8527839
TI  - VEGF-mediated tumour angiogenesis: a new target for cancer therapy.
AB  - Considerable evidence is gathering for the involvement of vascular endothelial
      growth factor (VEGF) in the vascularization and growth of primary tumours as well
      as in the formation of metastases. The expression of VEGF depends on activated
      oncogenes and inactivated tumour suppressor genes as well as several other
      factors (e.g. growth factors, tumour promoters and hypoxia). Substantial
      expression of the receptors for VEGF is restricted mainly to the tumour blood
      vessels. The causal involvement of this angiogenic factor in the progression of
      disease has been successfully evaluated by means of monoclonal antibodies against
      VEGF, dominant-negative receptor mutants and the use of antisense
      oligonucleotides against the VEGF mRNA. Thus, the VEGF signalling system seems to
      be an appropriate target to inhibit tumour angiogenesis and metastases formation.

PMID- 8527840
TI  - Recombinant proteins for medical use: the attractions and challenges.
AB  - Recombinant proteins that have survived the challenges of process development and
      clinical trials are becoming blockbuster medical products. Growth factors,
      enzymes and antibodies are being improved by mutational approaches, fused with
      other proteins, and even chemically modified in vitro. Drug development and
      testing approaches have advanced, and proteins produced in transgenic animals are
      new becoming available. Future protein products might include cancer vaccines and
      therapies for a variety of genetic diseases, but alternative treatments involving
      gene therapy or small synthetic compounds will provide competition.

PMID- 8527841
TI  - Interferon-beta treatment of human disease.
AB  - After nearly 20 years in the clinic, the benefits of interferon-beta treatment in
      specific disease states are being recognized increasingly. Two major clinical
      studies completed within the past two years have firmly established the use of
      this drug in the treatment of multiple sclerosis. Its therapeutic activity in
      several indications, including acute and chronic viral hepatitis, has also been
      demonstrated; however, the general use of interferon-beta in these settings
      awaits the results of ongoing studies and the development of practical dosing
      regimens.

PMID- 8527842
TI  - The new generation of recombinant human hematopoietic cytokines.
AB  - In the past year, the most exciting development in the field of hematopoietic
      growth factors has been the identification of the platelet-inducing factor Mpl
      ligand. Administration of recombinant Mpl ligand may alleviate the potential for
      hemorrhagic complications following cancer therapies. Stem cell factor continues
      to be studied clinically in the mobilization of peripheral blood cells for
      transplantation.

PMID- 8527843
TI  - Recent advances in liposomal drug-delivery systems.
AB  - Liposomal drug-delivery systems have come of age in recent years, with several
      liposomal drugs currently in advanced clinical trials or already on the market.
      It is clear from numerous pre-clinical and clinical studies that drugs, such as
      antitumor drugs, packaged in liposomes exhibit reduced toxicities, while
      retaining, or gaining enhanced, efficacy. This results, in part, from altered
      pharmacokinetics, which lead to drug accumulation at disease sites, such as
      tumors, and reduced distribution to sensitive tissues. Fusogenic liposomal
      systems that are under development have the potential to deliver drugs
      intracellularly, and this is expected to markedly enhance therapeutic activity.
      Advances in liposome design are leading to new applications for the delivery of
      new biotechnology products, such as recombinant proteins, antisense
      oligonucleotides and cloned genes.

PMID- 8527844
TI  - Innovative approaches to gene therapy.
AB  - The past year has witnessed several advances in the development of targeted, cell
      specific gene delivery systems of both viral and non-viral origin. Progress has
      been made in understanding the cellular mechanisms of nuclear import, and novel
      sequence-specific integrases have been developed that mediate insertion of DNA
      molecules into specific target sequences. Knowledge of the mechanisms by which
      herpes simplex virus and Epstein-Barr virus escape from immune surveillance has
      also advanced significantly; this may be exploited to reduce the immunogenicity
      of certain therapeutic gene products.

PMID- 8527846
TI  - Pharmaceutical biotechnology.

PMID- 8527845
TI  - What's in a gene: using genetic information for the design of clinical trials.

PMID- 8527847
TI  - Hormonal control of the biosynthesis of hamster oviductin.
AB  - In several mammalian species, the epithelial secretory cells of the oviduct
      synthesize and secrete specific glycoproteins that become associated with the
      zona pellucida of the ovulated oocyte. These glycoproteins are collectively
      designated as oviductins. A monoclonal antibody directed against hamster
      oviductin was used to study the ontogeny of this glycoprotein. Indirect
      immunofluorescence experiments performed on sections of hamster oviduct revealed
      that the glycoprotein begins to be secreted in 10-day-old females and that all of
      the oviductal secretory cells showed fluorescent staining by day 14. The
      intensity of the immunofluorescence reaction reached a maximum in the 28-day-old
      females. The oviducts of the 7-day-old hamster incorporated [35S]methionine in
      vitro into several proteins; however, the production and secretion of detectable
      amounts of radiolabeled oviductin only began at 14 days of age and reached a
      maximum at day 28 of age. It appears that the ontogeny of oviductin parallels the
      hormone dependent changes leading to sexual maturation and that its maximum
      secretion is already established at the time of the first ovulatory cycle. These
      results are substantiated by the fact that the production of oviductin is induced
      in estradiol-treated, but not progesterone or non-treated prepubertal animals, as
      determined by indirect immunofluorescence experiments.

PMID- 8527848
TI  - Elaboration of an oviductin by the oviductal epithelium in relation to embryo
      development as visualized by immunocytochemistry.
AB  - The hamster oviduct secretes a high molecular weight antigen that belongs to the
      family of glycoproteins known as oviductins. In the present study, using immuno
      electron microscopy, we examined the location of this hamster oviductin-1 (Hm Ov
      1) in hamster oviductal oocytes and early embryos up to the blastocyst stage. The
      immunoreactive pattern of Hm Ov-1 changes markedly during the embryo development.
      In oviductal oocytes prior to fertilization, Hm Ov-1 was associated exclusively
      with the zona pellucida. Following fertilization, immunolabeling was detected in
      the perivitelline space and over the plasma membrane of 2-cell, 4-cell, and 8
      cell embryos as well as young blastocysts. The change of the immunoreactive
      pattern was accompanied by the formation of an abundant number of coated pits,
      endocytic vesicles, multivesicular bodies, and lysosomal-like structures which
      were strongly labeled by gold particles. These immunogold-labeled cytoplasmic
      organelles characteristic of the endosomal-lysosomal apparatus were particularly
      evident in 2-cell, 4-cell, and 8-cell embryos and showed a decrease in number in
      the blastocysts. The close resemblance between the labeled flocculent material
      detected in the perivitelline space and that found in the zona matrix of early
      embryos and blastocysts suggested that the Hm Ov-1-associated electron-dense,
      flocculent material in the perivitelline space originated from the zona pellucida
      and was later endocytosed by the blastomeres through coated pits and endocytic
      vesicles. The detection of Hm Ov-1 in numerous multivesicular bodies and
      lysosomal structures indicated that the oviductin is eventually degraded.
      Although the exact functional role of Hm Ov-1 is not known, the presence of a
      copious amount of Hm Ov-1 in early hamster embryos may be ascribed to a special
      relationship between this particular oviductin and embryo development.

PMID- 8527849
TI  - Lectin binding and identification of sialic acid acceptor sugars in rabbit
      oviduct under hormone administration.
AB  - Localization of individual glycosidic residues and sialic acid acceptor sugars
      was investigated by conjugated lectins in the rabbit oviduct under physiological
      hormonal conditions and human chorionic gonadotropin (HCG) administration.
      Ampulla and isthmus were found to exhibit lectin binding profiles typical of each
      hormonal stage. Two different sialylated glycomolecules were identified within
      the epithelial lining; in particular, sialoglycoconjugates characterized by the
      terminal sequence sialic acid-galactose were visualized in the secretory cells
      and the sialic acid-N-acetylgalactosamine terminal disaccharides were localized
      on both ciliated and secretory cells of the entire oviduct. Surface and
      cytoplasmic sialoglycoconjugates were also found to exhibit a differential
      behaviour inside the two oviduct tracts examined. Present findings further
      supported the idea that in ampulla and isthmus, the greatest modifications
      consequent to hormone treatment take place at different times.

PMID- 8527850
TI  - Oviduct during early pregnancy: hormonal regulation and interactions with the
      fertilized ovum.
AB  - The cyclic fluctuations in circulating levels of 17 beta-estradiol and
      progesterone that occur during the menstrual or estrous cycle are responsible for
      dramatic, cyclic changes in the epithelial lining and secretory status of the
      mammalian oviduct. The timely transition in the synthesis and release of oviduct
      proteins, due to the ovarian steroids, and their interactions with oocytes,
      sperm, and the fertilized ovum underscore key biological events during gamete
      interactions and early embryonic cleavage. The regulation of these secretory
      alterations during the first few days of pregnancy is discussed with respect to
      the influence of the ovarian steroids, their interactions with the embryo
      microenvironment, and the possible ways in which they may mediate the critical
      reproductive events of fertilization and embryo development.

PMID- 8527851
TI  - Isolation, cell culture, and characterization of oviduct epithelial cells of the
      cow.
AB  - This report describes an easy method of isolation and cell culture of the
      epithelial cells of cow oviduct. Incubation of cow oviduct with 0.1 mg/ml
      collagenase in the lumen for 90 minutes helped to dislodge large numbers of
      ciliated and secretory epithelial cells. The isolated cells, when seeded on
      plastic, proliferated very quickly and became confluent in 8-10 days in 35 mm
      Petri dishes. The isolated ciliated cells which attached to the plastic dish lost
      their cilia after 4-5 days in culture. The cultured epithelial cells were keretin
      positive. The isolated bovine oviduct epithelial cells, when cultured on plastic
      precoated with 10 mg/ml matrigel, organized themselves into hollow tubes or
      spheres with microvilli directed towards the lumen. The epithelial cells seeded
      on 2 mg/ml matrigel became subconfluent in 15-20 days after seeding. The
      histoarchitecture of the secretory cells growing in vitro on matrigel resembled
      that of intact oviduct secretory epithelial cells. Occasional ciliated cells
      containing large number of mitochondria were observed in the monolayer cultured
      on 2 mg/ml matrigel substratum but possessed few cilia. The oviduct epithelial
      cells cultured on 2 mg/ml matrigel incorporated 35S-methionine linearly into
      protein up to 8 hours in the presence of estradiol or progesterone. The
      fluorograph of the newly synthesized proteins indicated the presence of an
      additional 60 kd protein in the cell extract of epithelial cells incubated with
      estradiol.

PMID- 8527852
TI  - Bovine oviductal epithelial cells (BOEC) and oviducts: I. For embryo culture. II.
      Using SEM for studying interactions with spermatozoa.
AB  - The oviduct (uterine tube) plays a major role in reproduction. It is a dynamic
      organ which selectively permits a few sperm to undergo capacitation and reach the
      oocyte which has continued to undergo maturation following ovulation. Then
      following fertilization the embryo undergoes cleavage before arriving in the
      uterus. Extensive information has become available from in vitro studies on
      oocytes as well as spermatozoal interactions with oviductal cells. Bovine oviduct
      epithelial cell (BOEC) monolayers with simple media provide an environment in
      which zygotes can be cultured to blastocysts in 6 days with cell numbers
      essentially equivalent to blastocysts grown totally in the donor animal. These
      yield normal pregnancy rates upon transfer. The simple protein-free media
      currently under test hold promise for elucidating specific requirements of the
      preimplantation embryo and these defined conditions facilitate many related
      studies on in vitro fertilization and genetic engineering of embryos. The second
      part of this paper is an extensive study on the interaction of fresh and frozen
      thawed bull spermatozoa with BOEC and segments of intact oviducts as viewed by
      SEM. Both types of oviductal cells were incubated at 39 degrees C for 0, 3, 6,
      and 9 hours, using material obtained from periovulatory cows. Sperm attached
      immediately to both types of epithelium and reached a peak at 3 hours. They were
      found primarily in the furrows of the intact oviducts. Secretory droplets
      appeared rapidly on the anterior portion of the sperm head and acrosomal changes
      were evident in 3 hours, similar to those reported in vivo. Changes were more
      rapid with frozen-thawed sperm.

PMID- 8527853
TI  - Improved antigenic preservation of plant tissue by low temperature processing in
      LR white resin.

PMID- 8527854
TI  - Myelin mutants: new models and new observations.
AB  - The myelin mutants have been extensively used as tools to study the complex
      process of myelination in the central and peripheral nervous system. A
      multidisciplinary approach to the study of these models ultimately allows a
      correlation to be made between phenotype and genotype. This correlation may then
      lead to the formation of new hypotheses about the functions of the products of
      genes involved in myelination. This review presents a number of new myelin
      mutants which have recently been described. The species involved include mouse,
      rat, rabbit, hamster, and dog models. The genetic defect has not been elucidated
      in all of these animals, but most have been characterized clinically and
      pathologically, and, in some cases, biochemically. In addition, a better known
      myelin mutant, the trembler mouse, is discussed. Recent molecular findings have
      brought this fascinating mutant to the forefront of the field of peripheral
      nervous system research. The range of abnormalities in the mutants described in
      this review includes defects in specific myelin proteins, suspected abnormalities
      in membrane formation, and apparent defects of the oligodendrocyte cytoskeleton.
      These findings underscore the complexity of the myelination process and highlight
      the numerous ways in which it can be disrupted.

PMID- 8527855
TI  - Murine model of genetic demyelinating disease: the twitcher mouse.
AB  - Twitcher mouse is an authentic murine model of human genetic demyelinating
      disease, globoid cell leukodystrophy (GLD), or Krabbe disease. Since its
      discovery at the Jackson Laboratory (Bar Harbor, ME) this model has been used
      extensively for the morphological, biochemical-enzymatic studies to clarify
      pathogenesis and also for therapeutic manipulation of genetic demyelinating
      disease in humans. As a result of these studies, now we know that (1) GLD is
      caused by a deficiency of lysosomal enzyme galactosylceramidase, and a toxic
      metabolite, psychosine, accumulates in the tissue, including the nervous system,
      damaging myelin forming cells and resulting in secondary demyelination; (2)
      morphological features of demyelination and associated cellular reactions in
      demyelination in this mutant are similar to those seen in autoimmune or toxic
      demyelination; and (3) with enzyme supplementation provided by bone marrow
      transplantation, remyelination occurs to some extent in demyelinated fibers in
      both central and peripheral nervous systems of twitcher mouse.

PMID- 8527856
TI  - Two models of multiple sclerosis: experimental allergic encephalomyelitis (EAE)
      and Theiler's murine encephalomyelitis virus (TMEV) infection. A pathological and
      immunological comparison.
AB  - Theiler's murine encephalomyelitis virus (TMEV) infection and experimental
      allergic encephalomyelitis (EAE) are considered among the best models of human
      multiple sclerosis (MS). In both models, clinical disease is characterized by
      paralysis, while pathological changes consist of inflammatory demyelination. In
      both models there is a genetic influence on susceptibility/resistance to the
      development of disease. This has been thoroughly studied in TMEV infection, and
      it has been found to depend on both major histocompatibility complex (MHC) and
      non-MHC genes. At least four genes have been so far identified. Because of this
      genetic influence, some strains of mice are more susceptible to both clinical and
      pathological changes than others, and susceptibility appears to best correlate
      with the ability of a certain murine strain to develop a delayed-type
      hypersensitivity (DTH) response to viral antigens. We have also observed that
      even among mice which are equally susceptible clinically, striking differences
      may be seen under pathological examination. These consist of different gradients
      of severity of inflammation, particularly in regards to the macrophage component.
      There is an inverse relationship between the number of macrophages, and their
      length of stay in the CNS, and the ability of mice to remyelinate their lesions.
      The most severe lesions are in SJL/J mice, and remyelination in this strain is
      extremely poor. The least severe lesions in terms of macrophage invasion are in
      strains such as NZW and RIIIS/J, and these are able to remyelinate lesions very
      successfully. Murine chronic relapsing EAE (CR-EAE) shows pathological changes in
      many ways similar to those in TMEV-infected SJL/J mice, although less severe in
      terms of degrees of macrophage infiltration and tissue destruction. Mice with CR
      EAE have a correspondingly limited ability to remyelinate their lesions. In both
      models the pathology appears to be mediated through a DTH response. However,
      while in EAE the DTH response is clearly against neuroantigens, the response in
      TMEV infection is against the virus itself. The end result in both models would
      be that of myelin destruction through a lymphotoxin-cytokine-mediated mechanism.
      The importance of the DTH response in both models is well illustrated by the
      effects of tolerance induction in EAE and TMEV infection to neuroantigens and
      virus, respectively. These are important models of human MS, since the current
      hypothesis is that a viral infection early in life, on the appropriate genetic
      background, may trigger a secondary misdirected immune response which could be
      directed either against myelin antigens and/or possible persistent virus(es).

PMID- 8527857
TI  - Spontaneous and induced remyelination in multiple sclerosis and the Theiler's
      virus model of central nervous system demyelination.
AB  - Remyelination in the central nervous system, originally thought to occur rarely,
      if ever, is now an established phenomena in multiple sclerosis patients. However,
      the extent of myelin repair is incomplete and limited. Experimental models of
      central nervous system demyelination provide an opportunity to study the cellular
      and molecular events involved in remyelination. These models may provide some
      clue to why remyelination in multiple sclerosis is incomplete as well as suggest
      potential methods to stimulate central nervous system repair. In this review we
      examine the morphological aspects of central nervous system remyelination and
      discuss both spontaneous and induced remyelination in multiple sclerosis and
      experimental models of central nervous system demyelination. We give special
      emphasis to the Theiler's virus model of central nervous system demyelination and
      its usefulness to identify therapeutic agents to promote remyelination. The role
      of immunoglobulins in promoting remyelination in both the Theiler's model system
      and in multiple sclerosis is discussed. Finally, we examine the potential
      physiological role of demyelination and remyelination and its relationship with
      clinical manifestations of central nervous system disease.

PMID- 8527858
TI  - Microwave fixation: understanding the variables to achieve rapid reproducible
      results.
AB  - The use of microwave irradiation for rapid chemical fixation of tissues in
      electron microscopy is a subject of current interest. The effects of water load
      size and location, sample placement in the oven cavity (hot or cold spots), and
      time on tissue preservation were examined. The use of a microwave container (4
      dram vial) encased in 60 ml of ice in a 100 ml polyethylene beaker and a 0% power
      setting between two 100% power settings (time interval) provided reliable control
      of temperature during microwave irradiation. High brightness neon lights provided
      a quick and easy method to identify and map hot and cold spots within the oven
      cavity. Using microwave irradiation for rapid glutaraldehyde and osmium tetroxide
      fixation of tissues (Pacific yew needle and mouse kidney and liver) for electron
      microscopy yielded preservation equal or better than routine immersion fixation
      when a time interval, a cold spot (as the sample location), and an ice-encased
      vial were used during microwave fixation. These adaptations provided reliable
      control of fixation conditions in an 800 watt laboratory microwave oven.

PMID- 8527859
TI  - Human lung volume, alveolar surface area, and capillary length.
AB  - We compare the effectiveness of morphometric methods for estimating lung
      parameters. Various stereological methods are applied on human lungs and
      described in detail. The lung volume was estimated by Cavalieri's principle and
      by fluid displacement. Both methods are reliable, but Cavalieri's principle is
      superior when systematic sections are needed or when volumes of parts of the lung
      are wanted. Point counting demonstrated that 87.5% of the lung is parenchyma,
      5.4% is vessel volume, and 7.1% is bronchia volume. Alveolar surface was
      estimated on vertical and isotropic uniform random tissue (IUR) sections. The
      capillary length and length density was estimated on projected images of vertical
      slices (Gokhale method) and on IUR sections. Only minute differences were found
      whether IUR sections or vertical sections were used. Of the total variation,
      approximately 2% was due to the stereological variation and approximately 98% was
      due to the biological variation on IUR sections and vertical sections. Estimates
      for volumes, surfaces, and lengths coming from model-based and design-based
      methods gave similar results for human lungs. In our hands, the design-based
      methods were easier to use and required less time. However, only the design-based
      methods offer the guarantee of an unbiased estimate.

PMID- 8527860
TI  - Moderate-temperature polymerization of LR White in a nitrogen atmosphere.

PMID- 8527861
TI  - Microsatellite instability in human cancer.
AB  - Tumorigenesis has made tremendous progress through the recent identification of
      widespread alterations in tumor genomes, manifested as microsatellite
      instability. Several genes causing microsatellite instability have already been
      identified. This was considerably facilitated by the knowledge of homologous DNA
      mismatch repair genes in bacteria and yeast. Correspondingly, the human genes are
      also tightly linked to DNA mismatch repair. In addition, recent research showed
      that there must be other--yet unknown--genes that might also cause the genotype
      of microsatellite instability. Microsatellite instability has also provided a
      model for the proposed existence of mutator phenotypes by giving an explanation
      as to how the high number of mutations observed in malignant cells might
      accumulate. This review focuses on these genes and our current knowledge of their
      role in tumorigenesis and/or tumor progression. In addition, the occurrence of
      microsatellite instability in a large variety of tumors is reviewed in detail.

PMID- 8527862
TI  - Induction of the differentiated phenotype in human colon cancer cell is
      associated with the attenuation of subcellular tyrosine phosphorylation.
AB  - In the present study we have determined membrane, cytosolic, and cytoskeleton
      associated tyrosine protein kinase (TPK) activity in human colon cancer cell
      lines exposed to (i) the differentiation-promoting agents sodium butyrate and 8
      chloro-cyclic-adenosine 3',5'-monophosphate (8-Cl-cAMP), (ii) tyrphostins,
      specific TPK inhibitors, or (iii) differentiation-inducing culture manipulations.
      Treatment of human colon cancer cell lines, LS 174T, COLO 205, and SW620, with
      sodium butyrate and 8-Cl-cAMP or tyrphostins AG-30 and AG-34, significantly
      attenuated TPK activity concomitantly with an increase in the activity of
      alkaline phosphatase, an enzymatic marker of intestinal cell differentiation. The
      differentiated phenotype induced in Caco-2 and HT-29 colon cancer cells by
      culture manipulation was associated with a significant decrease in cytoskeleton
      associated TPK activity and marked activity of alkaline phosphatase (AP).
      Electron microscopy and freeze-fracturing analysis of HT-29 cells showed that the
      gradual transition from the undifferentiated to the differentiated phenotype
      resulted in the acquisition of a distinct polarized morphology.
      Immunocytochemical phosphotyrosine analysis of cultured SW620 cells showed
      positive staining mostly localized in zones of focal contacts. A marked reduction
      in phosphotyrosine staining with notable changes in cell morphology was observed
      in SW620 cells exposed to tyrphostins. Cumulatively, the present results indicate
      that the induction of the differentiated phenotype in colon cancer cells is
      associated with a marked decrease in TPK activity and tyrosine phosphorylation.

PMID- 8527863
TI  - Induction of apoptosis by sodium butyrate in the human Y-79 retinoblastoma cell
      line.
AB  - The mode of cell death induced in the Y-79 human retinoblastoma cell line by
      sodium butyrate (SB), a short-chain fatty acid with potent inhibitory effects on
      the growth of many transformed cell lines, was investigated by fluorescence and
      transmission electron microscopy, agarose gel electrophoresis, and metabolic
      studies. While SB (< 1 mM) resulted in marked morphological differentiation,
      higher concentrations (1-4 mM) induced predominantly apoptotic involution in Y-79
      in a concentration-dependent fashion after a latent period of 24 h. Dying cells
      displayed the characteristic morphology of apoptosis accompanied by DNA laddering
      with agarose gel electrophoresis. Extensive cell necrosis was apparent with 0.5 M
      SB. Induction of apoptosis and DNA laddering by SB was reduced by putative
      inhibitors of RNA and protein synthesis, but not putative endonuclease
      inhibitors. These results are important for understanding the mode of action of
      sodium butyrate as a potential cancer chemotherapeutic agent.

PMID- 8527864
TI  - Influence of exogenous ras and p53 on P-glycoprotein function in immortalized
      rodent fibroblasts.
AB  - The ability of ras oncogenes and mutant p53 to activate reporter gene expression
      from human and rodent mdr1 gene promoters was described, although functional
      significance of this finding was unclear. We analyzed the influence of various
      forms of recombinant human ras and p53 on the mdr1 gene expression and P
      glycoprotein (Pgp) function in rodent immortalized fibroblasts. The ras genes, in
      addition to activation of exogenous human mdr1 gene promoter, caused an increase
      in (i) expression of endogenous mdr1 mRNA, (ii) Pgp activity as determined by
      flow cytometry analysis of Rhodamine 123 exclusion, and (iii) resistance of cells
      to the cytotoxic action of colchicine and some other drugs. To elucidate whether
      the same signalling pathway is responsible for multidrug resistance induced by
      various oncogenes and protein kinase C (PKC), we tested the effects of v-mos and
      the PKC agonist 12-O-tetradecanoylphorbol-13-acetate. Similarly to cells
      transformed by ras, a Rat1 subline transformed by the v-mos oncogene was
      characterized by decreased drug sensitivity. On the contrary, Rat1 cells treated
      with the protein kinase C agonist 12-O-tetradecanoylphorbol-13-acetate showed
      neither increased mdr1 mRNA expression nor stimulation of Pgp function.
      Introduction by retrovirus-mediated gene transfer of wild-type p53 into Rat1
      cells or into murine p53-deficient 10(1) and 10(3) cells did not change the Pgp
      function significantly, whereas in Rat1 cells transformed by activated N-ras or v
      mos, expression of wild-type p53 caused partial reversion of oncogene-induced
      drug resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527865
TI  - Doxorubicin and cyclosporin A affect murine lymphoid cells expressing different
      antigenic determinants.
AB  - Cyclosporin A (CsA) enhances the antitumor activity of doxorubicin (Dox) as well
      as that of some other cytotoxic drugs against drug-resistant tumor variants. In
      some cases, however, such combination treatments result in severe unexplained
      toxicities. In this study the possibility was explored that the effects of CsA
      and Dox on lymphoid cells may be instrumental, at least in part, in determining
      their toxicological effects. Subsets of spleen and thymus lymphoid cells, from
      mice with or without Dox or CsA treatment, were identified by flow cytometry
      based upon their plasma membrane antigenic determinants. The results indicate
      that there is essentially no cross-sensitivity/resistance between the two agents.
      The most Dox-susceptible cells were immature (non-proliferating) CD4+CD8+
      thymocytes and CD3-B220- as well as CD3-B220+ splenocytes. These populations were
      intact following CsA treatment, but the numbers of mature CD4+CD8- and CD4-CD8+
      cells were substantially reduced. Similar "mirror image" differences were found
      for other populations examined. When considered together, these findings suggest
      that in combination Dox and CsA would affect nearly all subsets of lymphoid
      cells, providing one possible explanation of why increased leukopenia, toxicity
      and immunosuppression are found after their combined administration. Since
      leukemias, lymphomas and, to a more limited extent, certain solid tumors express
      these same phenotypic markers, similar analyses should be considered for
      monitoring and perhaps even predicting neoplastic cell sensitivity to treatment
      with such agents.

PMID- 8527866
TI  - Screening of colon tumor cells and tissues for folylpolyglutamate synthetase
      activity.
AB  - Polyglutamylation of (anti)folates catalyzed by folylpolyglutamate synthetase
      (FPGS) determines the retention of these compounds in the cell. This feature is
      essential for the activity of folates (e.g., folinic acid) and antifolates (e.g.,
      methotrexate) in the treatment of cancer. A FPGS assay was developed using murine
      liver and was based on published methods, but had a novel analytic procedure.
      Tritiated glutamate and aminopterin served as substrates for FPGS, and after the
      reaction the mixture of substrates and products was separated by thin-layer
      chromatography. Results were verified by standard anion-exchange high performance
      liquid chromatography for folates. The assay was applied to measure the activity
      of FPGS in several cancer cell lines and human and murine (tumor) tissues. Cancer
      cell lines had a much higher activity (varying from 82 to 656 pmol diglutamate
      formed per hour per 10(6) cells) than murine bone marrow cells (35 pmol/h/10(6)
      cells). Murine gut mucosa had a very low FPGS activity compared to murine liver
      (7 vs. 24 pmol diglutamate/h/g wet weight), but the activity in murine colon
      tumors was comparable to or higher than that in liver (28-52 pmol diglutamate/h/g
      wet weight). A screening of 11 human colon tumors or metastases demonstrated that
      there was a large variation in FPGS activity in this tumor type, but overall the
      activity was higher in tumor tissue than in normal colon mucosa. The latter
      feature may increase the selectivity of antifolate-based chemotherapy of colon
      tumors. The FPGS assay described in this paper allows large-scale screening of
      cell lines and tissues, because of its rapid separation procedure by thin-layer
      chromatography.

PMID- 8527867
TI  - Reference listings in cancer research.

PMID- 8527868
TI  - Indirect effects in ecological interaction networks. II. The conjugate variable
      approach.
AB  - A new method called the conjugate variable approach for the analysis of indirect
      effects propagating through an ecosystem network is developed. For a given
      ecosystem of n species, the 2n variables representing the inflows and abundances
      of the n species are related in the n equations that define the system's steady
      states. There are 2n alternative ways of designating, for each species, either an
      inflow or an abundance variable as an independent variable and the other (i.e.,
      its conjugate variable) as a dependent variable. Each of these alternative ways
      defines a unique configuration of constraints in the influence propagation
      through the ecosystem network. In particular, designating as independent
      variables the inflow variables of all but two focal species leaves their
      abundance variables free to change, thus leading to the evaluation of the total
      effect between the two focal species. On the other hand, choosing their abundance
      variables as independent variables to fix prohibits influence to pass through any
      of these intermediate species, thus selectively evaluating the direct effect
      between the two focal species. Any other way between these two extreme cases sets
      partial constraints on influence propagation, thus evaluating a partial effect
      between the two species. Four categories of effects between two species--inflow
      to abundance, abundance to abundance, inflow to inflow, and abundance to inflow-
      can be distinguished and explicitly evaluated in terms of community matrix
      elements.

PMID- 8527869
TI  - Growth of nonnecrotic tumors in the presence and absence of inhibitors.
AB  - In this article a model for the evolution of a spherically symmetric, nonnecrotic
      tumor is presented. The effects of nutrients and inhibitors on the existence and
      stability of time-independent solutions are studied. With a single nutrient and
      no inhibitors present, the trivial solution, which corresponds to a state in
      which no tumor is present, persists for all parameter values, whereas the
      nontrivial solution, which corresponds to a tumor of finite size, exists for only
      a prescribed range of parameters, which corresponds to a balance between cell
      proliferation and cell death. Stability analysis, based on a two-timing method,
      suggests that, where it exists, the nontrivial solution is stable and the trivial
      solution unstable. Otherwise, the trivial solution is stable. Modification to
      these characteristic states brought about by the presence of different types of
      inhibitors are also investigated and shown to have significant effect.
      Implications of the model for the treatment of cancer are also discussed.

PMID- 8527870
TI  - Coherent potential approximation approach to electronic structure of DNA.
AB  - The electronic structure of DNA is theoretically investigated by use of the
      coherent potential approximation. Even when the sequence of the four kinds of
      bases is nonperiodic, guanine block forms the persistent highest valence band
      edge, and adenine block forms the persistent lowest conduction band edge state.
      According to the calculated joint density-of-states energy profiles, the site
      first attacked by the lowest excitation is adenine block. After this excitation,
      electrons are generated at adenine sites, and holes are generated at guanine
      sites. The resulting electronic structures of the valence band and conduction
      band suggest that the base complementarity in DNA produces the complementarity in
      the density-of-states divergences of the excited electrons and holes. This
      complementarity lowers the excitation instability in the DNA chains.

PMID- 8527871
TI  - On a compartmental analysis result.

PMID- 8527872
TI  - Indirect effects in ecological interaction networks. I. The chain rule approach.
AB  - A mathematical method for evaluating indirect effects propagated through
      ecosystems consisting of multiple species is developed. The time-backward
      expansion of the sensitivity matrix of a system at steady state represents the
      tracking back of the total effects received by species. Aggregating those
      portions of the total effect between two species that travel through a common
      path with various schedules gives the path partitioning of the total effect. From
      this path partitioning, a chain rule is derived that expresses the indirect
      effect transmitted through an individual path as the products of direct effects
      associated with the links constituting the path. The evaluation of indirect
      effects by this chain rule is applied to example systems to reveal the entire
      structure of influence propagation through the systems. The results of this
      application suggest three basic mechanisms through which indirect effects
      contribute to the complexity and contingency of species interactions: (i) the
      globalization of influence by bundles of long indirect paths, (ii) the
      amplification (or reduction) of effects by positive (or negative) cycles, and
      (iii) the alteration in sign of interactions between a pair of species due to the
      change in dominance among the effects carried by parallel paths connecting the
      species.

PMID- 8527873
TI  - Linear presentation of variable side-chain spacing in a highly diverse
      combinatorial library.
AB  - A synthetic library that presents potential pharmacophores in a linear fashion
      with variable spacing was designed (alpha, beta, gamma-library). To prove the
      concept, we synthesized a number of individual compounds as well as a model
      library. Diamino acids connected by amide bonds via their alpha- or side-chain
      amino groups were used to form the backbone (scaffold) of this library. The
      remaining amino group of the diamino acids were acylated by a variety of
      carboxylic acids, generating an appreciable diversity of compounds in this
      library. The compositions of compounds in the library were identified by reading
      a peptide tag synthesized concurrently with the library structures. This code
      contained the information regarding the carboxylic acid coupled, and the diamino
      acid and amino group to which the acid was coupled.

PMID- 8527874
TI  - Structure of human calcitonin gene-related peptide (hCGRP) and of its antagonist
      hCGRP 8-37 as determined by NMR and molecular modeling.
AB  - The solution structures of human calcitonin gene-related peptide (hCGRP, 37
      residues) and of its antagonistic fragment hCGRP 8-37 have been determined by two
      dimensional 1H nuclear magnetic resonance (NMR) spectroscopy and molecular
      modeling. Analysis of the double quantum filtered correlation spectroscopy, total
      correlation spectroscopy and nuclear Overhauser enhancement spectroscopy spectra
      led to a complete assignment and to the identification of more than 350 intra-
      and interresidue connectivities for each peptide. Molecular models were
      calculated by molecular dynamics and energy minimization using distance
      constraints. The structure of hCGRP is characterized by a rigid N-terminal
      disulfide-bonded loop followed by helix segments (Val8-Leu16), a gamma-turn
      (Ser19-Gly21) and several local hydrogen-bonded patterns. The structure of hCGRP
      8-37 is less defined than the structure of hCGRP and no helix structure is
      present. Molecular models of both peptides are consistent with the NH temperature
      coefficients and secondary chemical shifts of the alpha-protons. Hydrogen bonding
      with the disulfide-bonded ring appears to be critical for helix formation, both
      structural elements being essential for agonistic activity.

PMID- 8527875
TI  - Contribution of specific amino acid residues within the hFSH alpha 26-46 sequence
      region to FSH receptor-binding activity.
AB  - The role of specific amino acid residues within the sequence region between Leu26
      and Thr46 of the human follicle-stimulating hormone (hFSH) alpha-subunit in the
      FSH-receptor interaction has been investigated. Competitive binding activities of
      seven sets of synthetic peptides were evaluated with both FSH- and luteinizing
      hormone (LH)-radioreceptor assay procedures. Set 1 included two overlapping
      peptides (alpha 25-41 and alpha 31-45) spanning the alpha 26-46 region, while
      Sets 2-6 included peptides of different size or structure in which the alpha 26
      46 sequence was (i) sequentially truncated either from the N-terminus or from the
      C-terminus or both; (ii) alternatively reduced to a series of overlapping 13-mer
      peptides; or (iii) modified at the C-terminal Arg and Lys residues with
      substitution by Ala residues. In Set 7, synthetic peptides related to the parent
      alpha 26-46 peptide were prepared in which all the cysteine residues were
      substituted either singly or multiply with serine residues (i.e., alpha 26-46
      Cys28,31,32-->Ser28,31,32). The ED50 values of the parent alpha 26-46 peptide in
      the FSH-radioreceptor assay were 2 and 7 x 10(-5) M, depending on whether the C
      terminus was present as the amide or the free acid form, respectively. The
      substituted peptide alpha 26-46 (Cys28,31,32-->Ser28,31,32) was totally inactive
      in the FSH-radioreceptor assay. The truncation studies indicated that Cys28,
      Cys31 and Cys32 all contribute to the hormone-receptor interaction, with Cys32
      being the major contributory cysteine residue. Similar results were observed when
      these peptides were evaluated in the LH-radioreceptor assay where the ED50 value
      for the parent alpha 26-46 peptide was observed to be 2 or 3 x 10(-5) M,
      depending on whether the C-terminus was the amide or the free acid. The Cys31
      residue did not appear to contribute to the LH-receptor interaction; however,
      removal of Cys28 and Cys32 resulted in significant decreases in binding activity.
      The C-terminal truncation studies of the alpha 26-46 peptide revealed that Lys44
      contributes to FSH receptor binding activity but does not contribute to the LH
      receptor interaction. Truncation of the Arg42 residue or substitution of Arg42
      with alanine in the alpha 31-45 peptide sequence prepared as part of the Set 1
      synthetic peptides (i.e., the alpha 31-45 Arg42-->Ala42 peptide) or as part of
      the Set 6 peptide series, alpha 26-46 Arg42-->Ala42, confirmed the involvement of
      this residue in the LH-receptor interaction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8527876
TI  - Synthesis of an O-palmitoylated 44-residue peptide amide (PLTX II) blocking
      presynaptic calcium channels in Drosophila.
AB  - PLTX II, a presynaptic calcium channel blocker in Drosophila isolated from the
      plectreurys spider venom, is a 44-residue peptide containing ten Cys residues and
      an O-palmitoylated threonine amide at the carboxy-terminus. In this study, the
      palmitoylated peptide was synthesized in solution by applying our maximum
      protection strategy using the HF method at the final deprotecting step. Before
      designing the synthesis, we examined the stability of the palmitoyl moiety under
      the conditions for the synthesis of the peptide using several model peptides. The
      O-palmitoyl group was confirmed to be stable during elongation of the peptide
      bonds, but was partially removable during the deprotection reaction in HF. The
      depalmitoylation reaction in HF was temperature- and time-dependent. Therefore,
      the decision was made to protect the Asp residues with benzyl ester, since it is
      more susceptible to HF than cyclohexyl ester, which is now commonly used in the
      Boc-based, solid-phase synthesis. Thus, the HF reaction was carried out at -10
      degrees or -15 degrees C for 1 h in order to reduce the extent of the
      depalmitoylation reaction. The resulting palmitoylated and depalmitoylated
      products were separated, the remaining Acm groups were removed using Hg(OAc)2,
      and then the completely deprotected peptides were folded to their native forms.
      The final palmitoylated peptide was proven to be identical with the natural one
      using various HPLC systems and by bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527877
TI  - Detection of secondary amines on solid phase.
AB  - The detection of secondary amino groups in building blocks attached to solid
      phase using tetrachlorobenzoquinone (chloranil) was re-examined. A new procedure,
      about ten times more sensitive than the original method, has been developed.
      Except for N(p-tolyl)glycine, all secondary amino groups that were examined were
      detected reliably in a substitution range down to 2.8 micro eq/g. Protected
      imidazole in His(Trt) did not interfere with the detection method.

PMID- 8527878
TI  - Instability of side-chain protecting groups during MALDI-TOF mass spectrometry of
      peptide fragments.
AB  - Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry
      (MALDI-TOF MS), a well-suited method for the characterization of peptides and
      proteins, was used for analysis of protected peptide fragments. It is shown that
      acidic matrices, e.g. 2,5-dihydroxybenzoic acid, frequently used in MALDI-TOF MS
      of peptides, causes partial cleavage of acid-labile side-chain protecting groups.
      Because this effect is strongly related to the matrix used, the observed
      deprotection can be avoided by choosing an appropriate matrix such as 2,4,6
      trihydroxyacetophenone or 2-amino-5-nitropyridine. The advantage of neutral
      matrix compounds for MALDI-TOF analysis of protected peptides is clearly
      demonstrated, confirming the potential of MALDI-TOF mass spectrometry.

PMID- 8527879
TI  - [Longitudinal analysis of utilization of inpatient treatment based on insurance
      data of mandatory health insurance].
AB  - AIM: To investigate which of the routinely collected claims data from the German
      "Legal sickness funds" on hospital utilisation may be used, in addition to that
      prescribed by the legislator. DESIGN: We used claims data to study a cohort of
      sickness fund beneficiaries who were insured during the complete year 1992 (n =
      81,309). Six utilisation parameters, using the number of cases and in hospital
      days overall as well as diseases specific (i.e. readmission rates, in-hospital
      days per person with [at least] one hospital stay) were calculated. RESULTS:
      There are 88 persons with (at least) one hospital stay, 116 hospital cases and a
      total of 1306 in-hospital days per 1000 insured persons in the study cohort. The
      average hospital days per person (14.8 days) are ca. 30% higher than the average
      length of stay (11.2 days). Hospital utilisation increases with age. Hospital
      stays associated with ICD-239 (neoplasms of unknown origin) resulted in a higher
      than average number of hospital days in total although the mean length of stay is
      not above the average. This is due to a high readmission rate. Hospital stays
      associated with elective surgical procedures have a high prevalence rate but a
      low readmission ratio and short length of stay. CONCLUSION: The parameters
      related to insured persons, cases and specifically personal parameters of
      hospital utilisation allow a detailed analysis of hospital care; different
      utilisation and user patterns can be investigated and possible determinants of
      utilisation can be identified. After technical transformation, routine data of
      the sickness funds can be used to obtain information relevant for health care
      planners as well as for quality management.

PMID- 8527880
TI  - [Interrater reliability of expert assessment by the health insurance medical
      service in determining eligibility for disability benefits].
AB  - In this paper, we present the first study on the inter-rater reliability of a
      standardised examination of functional disability, employed by the medical
      service of the German statutory health insurance system ("Medizinischer Dienst
      der Krankenversicherung", MDK). 215 elderly adults (mean age 84) living in 6
      nursing homes in Munich were included in the study. They were assessed by three
      medical students and two nurses of the respective nursing homes using the
      standardised questionnaire of the MDK. Inter-rater reliability of both a summary
      judgement of disability and of single items, such as impairments in activities of
      daily living, was assessed by kappa-coefficients. Inter-rater reliability was
      higher for the overall assessment of disability (kappa = 0.82 between nurses,
      kappa = 0.57 between medical students) than for most single items. Reliability
      was particularly low for some items on mental status (such as "restlessness") or
      perceptions (particularly visual perception) which require clearer definition.
      This pattern was consistently observed for the two types of comparisons (inter
      students, nurse-nurse) and for different subgroups of the study population.

PMID- 8527881
TI  - [Health conferences--opportunities for cooperation between demands and reality].
AB  - The chances, to carry out health-political innovations on the communal level, are
      actually in a close manner connected with the development of on health related
      cooperation structures. Whether health politicians, experts or scientists, they
      all set their hope on the instrument of cooperation and coordination, to be able
      to solve better the urgent questions of health promotion and health care in the
      communities or regions. Conferences of health are they key-term for the necessary
      organizational frame, which should render possible an improved cooperation and
      harmonization between the actors of the health system. On the background of
      selected examples of practice of health conferences here will be discussed the
      conception and the problems of transformation as well as the necessary conditions
      of development.

PMID- 8527882
TI  - [The health of girls during puberty].
AB  - This report is based on many years of working experience in the field of health
      promotion and sexual education of girls. The hypothetically assumed relation
      between the subjective feeling of well-being and pubertal influences is reflected
      in figures. The results reveal strong irritations regarding bodily, affective and
      social factors which the girls have to cope with. High acceptance is documented
      for discussions about health and sexuality with a medical expert. Rubella
      vaccination is recommended as a starting point for activities of the Public
      Health Service in preventive work with girls in schools.

PMID- 8527883
TI  - [Multiple chemical sensitivity syndrome].
AB  - The multiple chemical sensitivity syndrome (MCS) is a novel constellation of
      symptoms in environmental medicine that has been extensively described and
      commented on in the USA. The main features of this syndrome are: multiple
      symptoms in different organ systems triggered by a variety of chemical
      substances, with relapses and exacerbations under certain precipitating
      circumstances at very low levels which do not cause any reactions in the
      population at large. There are no lab markers or specific investigative findings.
      This paper describes the historical development of the term MCS, its diagnostic
      criteria and pathophysiological aspects using 10 patient histories from our
      hospital.

PMID- 8527884
TI  - [Copper-induced liver cirrhosis in a 13-month old boy].
AB  - A micronodular liver cirrhosis with a massive accumulation of copper in
      hepatocytes was found in a 13-months old boy. The causal factor was due to the
      increased copper concentration within the drinking water, which caused liver
      disease of the boy who had been completely weaned at the age of four weeks. The
      cooper concentration found in the drinking water exceeded 12 mg/l after a twelve
      hour stagnation time; after several days of stagnation the highest measured
      concentration was 28.6 mg/l. This increase is caused by the combined effect of
      copper pipes and acidulous well water.

PMID- 8527885
TI  - [Tuberculosis in asylum seekers].
AB  - In this prospective study conducted by 9 Public Health Offices in North Rhine
      Westphalia 1992 to 1994, among the analysed 4058 asylum seekers aged 1-89 years
      the chest radiographs showed in 444 cases old specific changes and in 48 cases
      active tuberculosis. This was verified microbiologically. 81% of the evaluated
      tuberculin skin test were positive with variations between the different
      countries of origin, which is significantly higher than among persons born in the
      Fed. Rep. of Germany. A compulsory chest radiograph shortly after arrival and
      controlled curative or preventive chemotherapy programmes are urgently needed.

PMID- 8527886
TI  - [The Lee-Carter model of the prognosis of mortality in Germany. Berlin Public
      Health Research Group--partial project "Goals and Goal Indicators for Public
      Health in East and West Berlin"].
AB  - A model for forecasting mortality developed by Lee and Carter is applied to data
      of West Germany. The logs of the age-specific death rates are modeled as a linear
      function of an unobserved mortality index using the singular value decomposition
      method. The forecasts are based on projections of all individual trends of the
      mortality rates. Applied to life expectancy at birth between 1969 and 1992 the
      model implies an increase of 2.2 years in life expectancy for men and 2.4 years
      for women in 2002.

PMID- 8527887
TI  - [Documentation in expert evaluation of disability status by the medical service
      of hospital insurance].
AB  - A first survey is given by the documentation of the examination for the statutory
      nursing care insurance. The first part of the report contains the complete
      tabulated results of the Federal Republic of Germany. Furthermore a graphical
      comparison of elected federal states has been statistically evaluated and is
      commented upon.

PMID- 8527888
TI  - [Environmental medicine consultation as a responsibility of Bavarian public
      health service].
AB  - Several working groups of the "Academy of Public Health in the Bavarian State
      Ministry of Labour and Social Affairs, Family, Women and Health" are asked to
      make suggestions for quality assurance in the fields of activity of the public
      health services. A first conception is now brought up for discussion by the
      "Working Group for Quality Assurance in Environmental Medicine". Necessarily, it
      is based on the actual legal status, but it is also influenced by the political
      discussion in Bavaria concerning a new organisation of the public health services
      and the possibility to denationalise functions. The conception is meant to be
      part of an inventory of the functions in environmental medicine. Some suggestions
      for quality assurance are made.

PMID- 8527889
TI  - Epithelial-mesenchymal interactions in cancer. Introduction.

PMID- 8527890
TI  - Epithelial-mesenchymal transitions in development and tumor progression.
AB  - Epithelial-mesenchymal transitions play important roles in development and
      malignancy. Here we discuss molecular events in the control of such transitions:
      changes in cellular adhesion components, action of oncogenes and tyrosine kinase
      receptors, as well as activation of transcription factors. In development,
      epithelial-mesenchymal transitions take place in a temporally and spatially
      controlled manner, whereas in tumors these changes are highly uncontrolled. Loss
      of epithelial character is typically observed late in progression of human
      carcinomas, and correlates there with the acquisition of invasive and metastatic
      potential.

PMID- 8527891
TI  - Tumor cell interactions with the vascular endothelium and their role in cancer
      metastasis.

PMID- 8527892
TI  - Stimulation and regulation of tumor cell motility in invasion and metastasis.
AB  - In this review, the role of extracellular factors in the stimulation and
      regulation of tumor cell motility are discussed. Tumor cells respond in a motile
      fashion to a variety of external ligands including autocrine motility factors,
      growth factors, and components of the extracellular matrix. Since tumor cell
      motility is a necessary component of tumor invasion and metastasis, we speculate
      that these protein factors could play important regulatory roles in tumor
      motility at different stages of the metastatic cascade.

PMID- 8527893
TI  - Regulation of scatter factor (hepatocyte growth factor) production by tumor
      stroma interaction.

PMID- 8527894
TI  - Tumor-stromal cytokine interactions in ovarian neoplasms.

PMID- 8527895
TI  - Keratinocyte growth factor as a cytokine that mediates mesenchymal-epithelial
      interaction.
AB  - Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast
      growth factor family (FGF-7) with a distinctive pattern of target-cell
      specificity. Studies performed in cell culture suggested that KGF was
      mitogenically active only on epithelial cells, though from a variety of tissues.
      In contrast, KGF was produced solely by cells of mesenchymal origin, leading to
      the hypothesis that it might function as a paracrine mediator of mesenchymal
      epithelial communication. Biochemical analysis and molecular cloning established
      that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2
      gene. Many detailed investigations of KGF and KGFR expression in whole tissue and
      cell lines largely substantiated the pattern initially perceived in vitro of
      mesenchymal and epithelial distribution, respectively. Moreover, functional
      assays in organ culture and in vivo and analysis of agents regulating KGF
      expression reinforced the idea that KGF acts predominantly on epithelial cells.
      While the data do not implicate a KGF autocrine loop in neoplasia, paracrine
      sources of factor or ligand-independent signaling by the KGFR might contribute to
      malignancy. Alternatively, because of its differentiation-promoting effects, KGF
      may retard processes that culminate in uncontrolled cell growth.

PMID- 8527896
TI  - Stromal-epithelial interaction in type IV collagenase expression and activation:
      The role in cancer metastasis.

PMID- 8527897
TI  - Angiogenesis as a component of epithelial-mesenchymal interactions.
AB  - Here we review the role of angiogenesis as it pertains to the interactions
      between the epithelium and the mesenchyme, especially during tumor growth and
      metastasis. We illustrate and discuss several models of angiogenesis including
      endothelial tube formation on Matrigel. Finally, we examine angiogenic factors
      using the Matrigel model and investigate several other matrix molecules for their
      importance in angiogenesis and epithelial/stromal interactions.

PMID- 8527898
TI  - Mammary tumor fibroblasts are phenotypically distinct from non-tumor fibroblasts.

PMID- 8527899
TI  - Fibroblast subpopulations as accelerators of tumor progression: the role of
      migration stimulating factor.
AB  - Tumor progression is a relatively indolent process, with many years commonly
      intervening between the inception of an initiating genetic lesion and the
      development of overt malignant disease. We suggest that the perturbation of
      normal epithelial-mesenchymal interactions caused by the inappropriate presence
      of fibroblast subpopulations displaying various 'fetal-like' phenotypic
      characteristics may significantly alter the kinetics of tumor progression and
      hence enhance susceptibility to cancer development. In this communication, we
      review our own data indicating the presence of fetal-like fibroblasts in cancer
      patients and put these observations in the context of similar published reports.
      We then discuss our interpretation of these findings, emphasising the possible
      direct involvement of fetal-like fibroblasts in cancer pathogenesis and putting
      forward an epigenetic 'clonal modulation' model to account for their presence in
      cancer patients.

PMID- 8527900
TI  - Regulation of HGF and HGFR gene expression.
AB  - Hepatocyte growth factor and its receptor (the product of the c-met
      protooncogene) are believed to be necessary for the normal growth and development
      of many tissues and organs. This ligand/receptor system controls essential
      cellular responses such as cell proliferation and motility as well as
      morphogenesis and differentiation. HGF mRNA is expressed primarily in mesenchymal
      but not in epithelial cells while its receptor is predominately expressed in
      epithelial cells. This pattern of HGF and HGFR gene expression in combination
      with the unique biological effects of HGF on its target cells has led to the
      postulate that HGF is one of the long-sought mediators conveying cross-talk
      between the epithelial and stromal compartments of a given tissue. The expression
      of HGF and HGFR genes are unregulated in several types of human cancer;
      therefore, understanding the control mechanisms governing HGF and HGFR gene
      expression is of great clinical interest. Toward this goal, we have analyzed the
      effects of various physiological agents such as cytokines and hormones on the
      expression of HGF and the HGFR in a multitude of cell types in vitro. Moreover,
      we have cloned and analyzed the HGF promoter and its 5'-flanking region to
      uncover the basis for its inducible and cell-type specific expression at the
      transcriptional level. Our results indicate that HGF and HGFR gene expression is
      inducible and their expression is orchestrated in stromal and epithelial cells,
      respectively, by extracellular signals derived from steroid hormones as well as
      cytokines such as IL-1, IL-6, and TNF alpha.

PMID- 8527901
TI  - The role of scatter factor and the c-met proto-oncogene in angiogenic responses.

PMID- 8527902
TI  - Modulation of intercellular junctions of epithelia by scatter factor (hepatocyte
      growth factor).

PMID- 8527903
TI  - The Met-HGF/SF autocrine signaling mechanism is involved in sarcomagenesis.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) can elicit a wide variety of
      effects upon cells expressing its receptor, the tyrosine kinase proto-oncogene
      product Met, including mitogenicity, motility, and morphogenesis. Normally, met
      expression is restricted to epithelial cells and is activated in a paracrine
      fashion by HGF/SF secreted from cells of mesenchymal origin. In this chapter, we
      review data showing that: (i) met over-expression in HGF/SF-expressing NIH/3T3
      fibroblasts leads to sarcomagenesis and metastasis via an autocrine mechanism;
      (ii) Met-HGF/SF autocrine signalling occurs to a low level in normal fibroblasts
      and to a much greater extent in human sarcomas and sarcoma cell lines; (iii) met
      expression is enhanced as p53-deficient fibroblasts are passaged in vitro and
      (iv) met and HGF/SF over-expression are selected for during tumorigenesis of p53
      deficient late-passage fibroblasts. Thus, loss of p53 predisposes a mesenchymal
      cell to over-express met and high level Met-HGF/SF autocrine signaling in
      mesenchymal cells promotes both sarcomagenesis and metastasis through
      inappropriate induction of the pleiotropic responses to Met-HGF/SF stimulation.

PMID- 8527904
TI  - Gunshot wounds to the head in an urban setting.
AB  - The literature reveals several ominous trends in firearm injuries in the United
      States. The crack epidemic of the mid-1980s, the increasing availability of
      handguns and more lethal weapons, and, particularly in Southern California, the
      rise of gang violence have all contributed significantly to this trend. Although
      the crack epidemic seems to have abated, the weapons it produced and the criminal
      elements it encouraged are still around. Many public health experts have
      advocated gun control as a means to stop this violence, and they have several
      compelling examples to justify their efforts. Gun control, however, is beyond the
      scope of this article. Neurosurgeons can have some effect at the local level on
      gang violence, however. The University of Southern California Department of
      Neurological Surgery has been working with the Think First Organization and
      Community Youth Gang Service Organization to reach out to children before they
      become involved with the gangs. These organizations are also working with the
      justice system to reform young people already involved with gangs. The hope is
      that these patterns of violence can be arrested on the community level.

PMID- 8527905
TI  - Characteristics of cerebral gunshot injuries in the rural setting.
AB  - The rural CGW population has not yet undergone the metamorphosis experienced by
      its urban counterparts. Reminiscent of a past era, suicides far outweight
      homicides. Although many rural firearm injuries involve hunting accidents, these
      comprise only a small fraction of CGW at best. Similarly, although many rural
      firearm injuries involve shotguns or rifles, few CGW result from these weapons.
      Although the number of patients is small, those with shotgun or rifle injuries
      manifest lower mortality rates. The authors have confirmed the notion that
      caliber of civilian weapons is difficult to correlate with outcome. The
      geographic size of the rural catchment area is an important consideration because
      it must select a population able to withstand transfer. The authors noted an
      inverse relationship between length of time before arrival at the facility and
      mortality. The selection phenomenon probably accounts for the reduced mortality
      found in the authors series versus most others. Prognostic features of individual
      gunshot wounds are likely to be similar among varied populations when
      circumstances of the injury are matched. Thus, one expects similar features on
      initial examination and CT scan to have similar predictive value. The authors
      confirmed that CGS and specific deficits were strong predictors of outcome. No
      patient with a GCS score of 5 or less on admission survived. Absent pupillary
      response, absent brain stem function, presence of respiratory drive or cough
      only, and posturing were strong indicators of impending death. The authors
      confirmed the prognostic value associated with CT evidence of intraventricular
      hemorrhage, transventricular trajectory, transtentorial herniation, massive
      edema, and bihemispheric injury. Interestingly, presence of extensive facial
      fractures, an indicator of trajectory, suggested better outcome. Subarachnoid
      hemorrhage did not reach prognostic significance. Roughly half of the authors'
      patients had positive serum ethanol levels, although the test was unable to
      discern prognosis. Abnormality of any coagulation parameter and frank
      disseminated intravascular coagulation were correlated with poor outcome.
      Likewise, thrombocytopenia occurring within the first 24 hours was an indicator
      of poor prognosis. Although prophylactic antibiotics were not used in all cases,
      the authors encountered no deep or superficial infections in surviving patients.
      The prevalence of seizures in the authors' series despite prophylactic AED is
      unusually high. This feature merits further study.

PMID- 8527906
TI  - The perspectives of violent street gang injuries.
AB  - Street gang violence has become a major public health problem in the United
      States, especially in the inner city. To prevent gang violence, one must
      understand the many facets of violent street gang activity and the psychological
      effects of gang violence on individuals as well as on the community. Further, one
      must have an understanding of the root causes of violent street gang formation,
      the relationship of firearms to gang violence, and the medical cost of these
      types of injuries. Prevention should begin with alleviating the root causes of
      violent street gang formation and include breaking the bonds of violent street
      gang membership. Adults acknowledge a societal obligation to protect and guide
      children and adolescents as an investment in the future. Because both children
      and adolescents lack judgment and experience, they cannot be expected to avoid
      injury and violence on their own. Although the financial cost of preventing gang
      violence would not be insignificant, the savings in terms of lives and medical
      expenditure would be immense. Unless steps are taken to end the physical and
      psychological trauma, regions of the United States, such as Los Angeles County,
      will not be safe from the effects of gang violence.

PMID- 8527907
TI  - Experimental missile wounding of the brain.
AB  - If a missile penetrates a cerebral hemisphere and does not severely disrupt the
      brain or transit a vital brain structure, it is hypothesized that the indirect
      effect of ordinary pressure waves set up by the interaction of missile and tissue
      and that impinge on brain stem respiratory nuclei determines life or death. The
      likelihood of fatal apnea is a direct function of missile energy of deposit
      within the brain. With brain wounding, a reduction in CO may also occur, but
      missile energy required to produce a significant CO decrease is in excess of that
      required to produce respiratory problems. Unless the individual managed to
      survive a period of apnea or respiratory resuscitation occurred, the effects of
      apnea would overshadow any CO decreases. Although transmitted ordinary pressure
      waves might interfere with the reticular activating system within the brain stem
      and produce persistent coma, specific long-lasting neurologic defects from a
      missile wound usually result from direct missile damage to the cerebral cortex or
      cortical projections. In designing treatments for missile wounds of the brain,
      two distinct entities must be kept in mind: the brain stem and the cerebral
      cortex. To decrease the immediate mortality from brain wounding, prompt treatment
      has to be devised to aid dysfunctional respiratory nuclei and possibly cardiac
      control nuclei. To decrease long-term neurologic morbidity, drug therapy has to
      be instituted to help injured cerebral cortical neurons for days to weeks after
      wounding. Totally different strategies and drugs may be needed to treat the brain
      stem as opposed to the cerebral cortex.

PMID- 8527908
TI  - Options for cerebral protection after penetrating head injury.
AB  - The medical management of secondary brain injury is entering a new era in which
      the fruits of labor in the laboratory are paying off in the form of legitimate
      agents for use in human trials. As more about pathophysiology of traumatic
      ischemic brain injury becomes known, more effective means for pharmacologic
      intervention and neuronal salvage will emerge, and optimism is high that we are
      approaching an era that will witness improvements in functional survival that
      have been heretofore unwitnessed.

PMID- 8527909
TI  - Cerebral hemodynamic disturbances following penetrating craniocerebral injury and
      their influence on outcome.
AB  - Available data on the subject of cerebrovascular dynamics after penetrating
      craniocerebral injury and their effect on outcome were reviewed. Following
      penetrating injury, CBF is depressed, as is cerebral metabolism. This decreased
      flow likely is associated with poor outcome as previously shown in closed head
      injuries. A phenomenon interrelated with a decreased blood flow is posttraumatic
      vasospasm. Vasospasm occurs in a significant percentage of patients as
      demonstrated both by TCD and angiography, and there is a strong relationship with
      SAH. Vasospasm following penetrating injury has an onset and time course similar
      to that seen in both closed head injury and aneurysmal SAH. Vasospasm following
      penetrating craniocerebral injury may be a cause of secondary ischemic injury,
      but further study is needed before the prognostic significance of this phenomenon
      is defined. For now, drawing a parallel with closed head injury and aneurysmal
      SAH, it can be inferred that vasospasm following cranial gunshot wound may be an
      important pathophysiologic factor. Because interventions are available to combat
      vasospasm, including medications (e.g., nimodipine), volume expansion, and
      elevation of blood pressure, the authors believe that identification and
      treatment of this potentially damaging condition are compelling, especially in
      patients whose CT scans demonstrate SAH.

PMID- 8527910
TI  - The radiologic evaluation of craniocerebral missile injuries.
AB  - A brief overview of the imaging findings in craniocerebral missile injury is
      presented here. CT scanning has established itself as the primary imaging
      modality for the complex injuries seen in CMI as well as its acute and delayed
      complications. Plain x-ray, angiography, and magnetic resonance imaging have more
      limited but sometimes important roles in the management of these injuries. With
      regard to outcome prediction, imaging has also proved to be of some, albeit
      limited, usefulness, primarily as adjuncts to clinical criteria such as the GCS.
      Future research with CT as well as magnetic resonance imaging will likely expand
      the clinical role of these modalities, particularly in the realm of outcome
      analysis.

PMID- 8527911
TI  - Multivariate analysis and prediction of outcome following penetrating head
      injury.
AB  - Schemes for predicting outcome in craniocerebral missile injury have ranged from
      Cushing's analysis that was based on the physical characteristics of the injury
      to complex logistic analyses that incorporate radiographic, laboratory, and
      clinical data. Generation of predictive scales is discussed, focusing on the
      utility of the Glasgow Coma Scale (GCS) score at presentation, presence or
      absence of coagulopathy, and radiographic evidence of the volume and type of
      tissue damage.

PMID- 8527912
TI  - Patients with Glasgow Coma Scale scores 3, 4, 5 after gunshot wounds to the
      brain.
AB  - Even this information is only partial. To study fully the effects of treatment
      would require optimal care at all points from time of injury, including rapid
      prehospital resuscitation, rapid transport to an optimally equipped and staffed
      hospital, immediate evaluation and treatment of the initial injury and all
      complications, rapid and comprehensive rehabilitation, and supportive and
      flexible home and work settings for the patient on discharge. Patients would need
      to be stratified for premorbid characteristics, including intelligence, personal
      traits, and training. Prolonged follow-up, possibly for several years, would be
      required to determine true outcome. No current study contains sufficient numbers
      of patients treated optimally and studied for prolonged periods, but this should
      be done. One way of looking at such patients is to decide that many should be
      treated to salvage a few. The other way of looking at them is that so many must
      receive care, at great emotional and economic cost to themselves and others, that
      such treatment is inappropriate for any of them. Treating all such patients would
      be a major undertaking. If most of these patients were treated vigorously, a
      great proportion of them would still die but probably not for a number of days.
      During this period, their families would be under extreme stress. Once stabilized
      and receiving ongoing care, some patients would enter a permanent vegetative
      state and survive for prolonged periods until their prognosis was clear and care
      was withdrawn, again causing family stress as well as high cost. Some would
      likely survive although impaired. The charges and real costs of care for all
      these patients would be tremendous. The question therefore arises as to how to
      decide what to do about caring for a large group of patients whose maximal care
      would be costly in emotional and financial terms, particularly at a time when it
      is recognized that resources for medical care are going to be limited. When
      discussing such patients as a group with a view toward developing practice
      guidelines, many considerations must be brought to bear. One consideration is the
      certainty of the prognosis in both a quantitative and a qualitative sense in an
      individual case. It is not clear that one can be certain in patients except when
      there are overwhelmingly unfavorable features. As has been noted, even patients
      who have been shot through the geographic center of the brain and are posturing
      can make excellent recoveries. This would push toward aggressive treatment for
      many patients. Decision making must therefore be considered in terms of
      bioethics. The major principle-based systems of bioethics are deontologic,
      arising from accepted principles, and utilitarian, arising from effect on
      outcome. A virtue-based ethic for physicians arising from "the caring bond and
      the public trust" is being revived as a balance to analytical ethics. A similar
      orientation from the point of view of patients is communitarian ethics, that is
      asking for only what is reasonable and not so much as might harm others. Some of
      the issues to be considered include the sanctity of life while taking into
      account the criteria for life--vegetative function versus some level of mental
      function. One must also review each decision from the viewpoints of all the
      parties involved--patients, family and friends, physicians, and society--in the
      context of a heterogeneous society in which individual rights and tolerance
      enforced by law are primary features. In the patients' terms, there is a desire
      and right to medical care to maintain a healthy productive life. Even if impaired
      to some extent, patients may still have an interest in living. Balancing benefits
      and burdens of life is a complex problem. There is also the right, based on
      patients' values, to refuse care if there is the wish not to take a chance of
      having a significantly compromised existence. Such declaration before injury
      should be honored...

PMID- 8527913
TI  - Penetrating injuries in the Vietnam war. Traumatic unconsciousness, epilepsy, and
      psychosocial outcome.
AB  - The WF Caveness Vietnam Head Injury Study includes over a thousand men who
      survived penetrating head injuries during the Vietnam War and on whom detailed
      medical and follow-up data are available. This population offers unique
      opportunities for the study of recovery from brain injury and of brain structure
      function relationships. The authors briefly review long-term outcome in this
      cohort with respect to traumatic unconsciousness, post-traumatic epilepsy, and
      elements of psychologic and psychosocial function, including returning to work.

PMID- 8527914
TI  - Care and variations in the care of patients with gunshot wounds to the brain.
AB  - A national survey revealed significant variations in a number of aspects of
      evaluation and surgical and nonsurgical treatment of patients with gunshot wounds
      to the brain. There could be many reasons for this. It would seem that there has
      probably not been sufficient research done to fully understand all aspects of
      such injuries. It also may be that different ways of caring for these patients
      provide equally satisfactory outcomes. Another problem that arises is that even
      with good information, there is difficulty in changing practice patterns that
      need to be understood better and made more effective. Based on the author's
      review and ethical considerations, certain basic and reasonable suggestions are
      made in this article.

PMID- 8527915
TI  - The prehospital and emergency department management of penetrating head injuries.
AB  - The prehospital and emergency department management of the patient with a
      penetrating cranial injury can be summarized by the following tenets: 1. Assume
      any alteration in level of consciousness to be a result of the brain injury and
      not from alcohol or illicit drug intoxication. 2. Have a low threshold to protect
      the patient's airway with endotracheal intubation and chemical paralysis if a
      surgical lesion is suspected, there is seizure activity, or the patient is too
      combative to obtain the necessary studies. 3. Always protect the cervical spine
      and do not remove the hard collar and spine board until adequate radiographs have
      been obtained and the patient is lucid enough to complain of any neck pain. 4. Do
      not delay CT scanning to obtain other studies in the presence of lateralizing
      neurologic findings. 5. Do not delay in obtaining neurosurgical consultation or
      in arranging transfer to a facility where definitive care can be provided. 6.
      Remember, first do no harm. The primary brain injury has already been done. The
      clinician maximizes preservation of viable brain tissue by preventing secondary
      injury.

PMID- 8527916
TI  - Military penetrating craniocerebral injuries. Applications to civilian triage and
      management.
AB  - Although facilities at many civilian centers far exceed those historically
      available to military neurosurgeons in the field, the principles derived from
      combat injuries continue to apply. It is hoped that there may be differences in
      salvageability at the margin owing to the availability of more sophisticated
      imaging and critical care monitoring techniques, neuroanesthesia, and the advent
      of possible pharmacologic neural salvage agents.

PMID- 8527917
TI  - Introduction to cerebral perfusion pressure management.
AB  - This article offers a broad review of cerebral autoregulation to help understand
      the principles of cerebral perfusion pressure (CPP) management. Discussed are
      cerebral autoregulation, Poiseuille's law, mannitol-induced hypertension and CPP,
      prognosis by CPP, management of CPP, and a summary of physiologic basis for CPP
      management.

PMID- 8527918
TI  - Management of traumatic aneurysms caused by high-velocity missile head wounds.
AB  - Trauma is implicated as a significant factor in the genesis of fewer than 1% of
      intracranial aneurysms. With the introduction of powerful neuroimaging
      technology, slowly but definitely, predictive variables are being added to solve
      this seemingly deadly pathology resulting from projectile injuries of the brain.
      This article discusses recent literature, nonprojectile penetrating traumatic
      aneurysms, iatrogenically induced traumatic aneurysms, materials and methods,
      traumatic aneurysms, and results.

PMID- 8527919
TI  - The management of penetrating vascular injuries.
AB  - Vascular disruption secondary to penetrating head trauma is most commonly in the
      form of surgically treatable intracranial and intracerebral hemorrhage. This
      article discusses the management of major cerbrobascular lesions associated with
      penetrating injuries to the neck and cranial vault, excluding traumatic
      aneurysms.

PMID- 8527920
TI  - Ethical decision making in managing trauma.
AB  - The major changes in health care delivery today further cloud the perspectives of
      patient autonomy, participation, and justice and the ideals of the virtuous
      practice of medicine. A Workable Integrative Negotiation approach with COAST
      permeating the medical setting and health agenda, however, can help promote
      effective and ethical participatory communication in medicine. Clearly,
      instituting such change in a non-surgical decision-making procedure requires a
      new culture among all participants. The case of traumatic injury provides an
      excellent back-drop for employing ethical decision making which in the long term
      can help usher in the most efficacious, ethical treatment for the individual,
      physician, and society. Additionally, today's omnipresent changes in medicine can
      help advance ethical directions in health-care decision making. For example
      adding ethical decision making and negotiation education in curricula for those
      in medicine, along with allied health professionals, and those who might become
      patient advocates or serve on ethics committees, can initiate a change in medical
      decision making. Full-fledged tort reform that allows all alternatives protects
      physicians and patients when the appropriate decision "to not treat or intervene"
      is rendered can be an important step toward a healthier society. Instituting an
      outcome-based reimbursement system among government and providers can serve as a
      quasi-selection process based on the superseding objectives of the community at
      large. Finally, a participatory citizenry (from physicians to patients to society
      at-large) that balances violence prevention, communication, innovation, community
      involvement, and appropriate treatment could advance optimal civic health. The
      challenge is to initiate such change with the communication principles outlined
      herein.

PMID- 8527921
TI  - Purification of acetylcholinesterase by tacrine affinity chromatography.
AB  - Acridine ligand affinity chromatography is an effective means of
      acetylcholinesterase (AChE) purification. However, the synthesis of these resins
      is laborious and expensive. We have developed an acridine ligand affinity resin
      that is easy to produce, inexpensive, and selective for AChE over
      butyrylcholinesterase. The resin is produced in a single synthetic step by
      attaching the aminoacridine tacrine to epoxy-activated Sepharose. AChE from
      bovine serum (59% yield), Torpedo electric organ (27-60% yield), and two
      commercial sources of eel AChE (> 92% yield) is purified using the affinity
      resin. One commercial source of eel AChE contains two proteins with molecular
      weights of 80 and 55 kDa upon purification, while two proteins with molecular
      weights of 55 and 25 kDa are isolated from the other commercial source,
      presumably representing degraded AChE. The degradation state of the commercially
      available eel AChE preparations did not influence their specific activities. The
      isolation of AChE from bovine serum results in a single 80-kDa protein. However,
      butyrylcholinesterase is not purified from the serum. Using the tacrine affinity
      resin, and 80-kDa AChE, solubilized from Torpedo electric organ membranes by
      protease digestion, can also be purified. Velocity sedimentation analysis of the
      Torpedo AChE reveals that the molecular forms isolated are either tetrameric or
      asymmetric when solubilized by collagenase or trypsin, respectively. Overall, the
      tacrine affinity resin which is simple and inexpensive to produce allows for the
      selective isolation of AChE from diverse biological matrices.

PMID- 8527922
TI  - Overexpression, purification, and characterization of Escherichia coli acyl
      carrier protein and two mutant proteins.
AB  - A synthetic gene of 237 bases encoding the 77-residue acyl carrier protein (ACP)
      from Escherichia coli, along with two mutant genes, ACP-I54V and ACP-A59V, were
      subcloned into the pET11a-pLysS E. coli overexpression system under the control
      of the bacteriophage T7 promoter. This efficient expression system and a
      simplified purification protocol yielded more than 120 mg/l of pure protein. The
      construct produced a mixture of holo-ACP and apo-ACP and two HPLC procedures were
      developed to separate the two species. This overexpression system allows cost
      effective growths of 13C- and 15N-labeled protein for structural and other
      studies on ACP. In the course of the work on the mutants of ACP, an apparent
      homologous recombination event led, in one case, to reversion to a wild-type
      protein, suggesting that precautions to prevent such reversion should be taken.

PMID- 8527923
TI  - A bifunctional vector suitable for both site-directed mutagenesis and recombinant
      expression of interferon-tau in Escherichia coli.
AB  - In order to produce workable quantities of a large number of mutant forms of
      recombinant ovine and bovine interferon-t (IFN-t), a bifunctional vector, pME-2,
      was developed, which combines a mutant selection system and a strong promoter
      providing controlled expression. An EcoRI/KpnI fragment containing the complete
      Trp promoter, a Shine-Dalgarno sequence, and an AT-rich region from the pTrp-2
      expression vector was inserted into the large fragment of EcoRI/KpnI-digested
      pALTER-1 plasmid, which had been modified by eliminating a ClaI site. The pALTER
      1 phagemid provides a highly efficient, antibiotic-dependent system for selection
      of mutant plaques. The existing T7 promoter was then eliminated from the
      recombinant phagemid to create the pME-2 vector. Ovine and bovine IFN-t genes
      lacking the coding region for the signal peptide, but with an ATG codon ahead of
      the open reading frame, were inserted into the multicloning site of pME-2.
      Following site-directed mutagenesis designed to produce elongations, truncations,
      and single and multiple amino acid replacements in the protein products, mutant
      genes were selected in Escherichia coli BMH 71-18 and efficiently expressed in E.
      coli JM-101 in response to the inducer of the Trp promoter indole acetic acid.
      The recombinant IFN were solubilized from washed inclusion bodies in guanidinium
      HCl and 2-mercaptoethanol and allowed to refold in aerated buffer. The procedure
      provides high yields of fully active, homogeneous IFN-t and can be accomplished
      within 1 week.

PMID- 8527924
TI  - Isolation of human serum IgA using thiophilic adsorption chromatography.

PMID- 8527925
TI  - Expression, purification, and characterization of human cytosolic serine
      hydroxymethyltransferase.
AB  - A cDNA which codes for human cytosolic serine hydroxymethyltransferase (Garrow et
      al., 1993, J. Biol. Chem. 268, 11910-11916) has been cloned into a pT7-7 vector
      as a NdeI-EcoRI insert. HMS174 (de3) cells were transformed with this plasmid
      and, after induction with isopropyl thiogalactoside, expressed a catalytically
      active serine hydroxymethyltransferase. The enzyme was purified and shown to be
      the expressed human enzyme by N-terminal amino acid sequencing. About 225 mg of
      pure enzyme can be obtained from a 20-liter culture. Spectral characteristics of
      the bound pyridoxal phosphate were essentially identical to the spectral
      properties of rabbit cytosolic serine hydroxymethyltransferase. Kinetic constants
      for the natural substrates L-serine and tetrahydrofolate were also similar to the
      values obtained previously for the rabbit cytosolic enzyme.

PMID- 8527926
TI  - Purification of progelatinases A and B by continuous-elution electrophoresis.
AB  - Progelatinases A and B were purified from HT1080-conditioned culture medium using
      a continuous-elution electrophoresis. Initially cell culture medium was ammonium
      sulfate precipitated. The concentrated proteins were affinity chromatographed on
      gelatin-Sepharose column. The bound gelatinases were eluted with electrophoresis
      sample buffer and subjected to continuous-elution electrophoresis. In a single
      run, under the standardized working conditions, the obtained fractions contained
      four purified enzymes--progelatinase A (M(r) 72,000), its activated forms (M(r)
      62,000 and M(r) 59,000), and progelatinase B (M(r) 92,000). Moreover, the
      continuous-elution electrophoresis allowed the enzymes separation from their
      respective inhibitors--TIMP-1 (M(r) 28,500) and TIMP-2 (M(r) 21,000). The
      purified progelatinases A and B demonstrated high specific activities (150-200
      U/micrograms).

PMID- 8527927
TI  - Cloning, expression, purification, and characterization of 2'-deoxyuridylate
      hydroxymethylase from phage SPO1.
AB  - 2'-Deoxyuridylate hydroxymethylase (dUMP-hmase) from phage SPO1 has been cloned
      and expressed in Escherichia coli. In crude extracts, the enzyme represents about
      25% of the soluble protein and has a higher specific activity than the most
      purified preparation yet reported. The enzyme was purified to homogeneity by ion
      exchange and hydrophobic chromatography. The subunits of dUMP-hmase are 45 kDa by
      SDS-PAGE and form dimers with a molecular mass of 89.2 kDa by analytical
      centrifugation. In addition to the normal reaction, dUMP-hmase catalyzes the 5,10
      methylene-5,6,7,8-tetrahydrofolate (CH2H4folate)-independent tritium exchange of
      [5-3H]dUMP for protons of water and dehalogenation of 5-bromo-2'-deoxy-uridine-5'
      monophosphate; the enzyme also forms a covalent binary adduct with pyridoxal 5'
      monophosphate and a covalent ternary complex with 5-fluoro-2'-deoxyuridine-5'
      monophosphate and CH2H4folate. Folic acid inhibits the tritium release catalyzed
      by dUMP-hmase in the presence of cofactor but has no effect on the catalysis of
      cofactor-independent tritium exchange.

PMID- 8527928
TI  - Expression of rat alpha 1-microglobulin-bikunin in baculovirus-transformed insect
      cells.
AB  - cDNA encoding rat alpha 1-microglobulin-bikunin was ligated into the transfer
      vector pVL 1392 and recombined with a wild-type baculovirus. The resulting alpha
      1-microglobulin-bikunin-encoding baculovirus was used to infect Trichoplusia ni
      (Hi-5) insect cells. The infected cells secreted alpha 1-microglobulin with
      maximal concentrations of 15 mg/liter 5 days after infection. The secreted
      proteins migrated upon SDS-PAGE as two major protein bands, 40 and 26 kDa,
      corresponding to alpha 1-microglobulin-bikunin and free alpha 1-microglobulin.
      The results suggested that the cells secreted mostly alpha 1-microglobulin
      bikunin, which subsequently was cleaved in the medium, yielding free alpha 1
      microglobulin. Both forms were isolated by monoclonal anti-alpha 1-microglobulin
      affinity chromatography, and alpha 1-microglobulin-bikunin separated from free
      alpha 1-microglobulin by gel chromatography. The yields of purified alpha 1
      microglobulin-bikunin and free alpha 1-microglobulin were approximately 1 and 5
      mg, respectively, per liter medium. Insect cell alpha 1-microglobulin displayed a
      size, shape, and charge heterogeneity similar to alpha 1-microglobulin isolated
      from rat urine. A panel of monoclonal antibodies raised against urinary alpha 1
      microglobulin from several different species bound to rat urinary alpha 1
      microglobulin and insect cell secreted alpha 1-microglobulin-bikunin and free
      alpha 1-microglobulin with approximately the same strength, indicating that the
      three proteins are folded in similar ways. The results of glycosidase treatments
      and lectin blotting indicate the absence of neuraminic acid but the presence of
      one N-linked oligosaccharide and an unspecified number of O-linked
      oligosaccharides in alpha 1-microglobulin-bikunin and free alpha 1-microglobulin.

PMID- 8527929
TI  - Expression and radiolabeling of human C-reactive protein in baculovirus-infected
      cell lines and Trichoplusia ni larvae.
AB  - Human C-reactive protein (CRP) is a member of the pentraxin family of proteins
      which are molecules composed of five identical subunits arranged in a planar
      configuration. In the present study a human CRP cDNA clone was ligated into the
      baculovirus vector pVL1393 which was used to establish a recombinant strain of
      BaculoGold Autographa californica multiple nuclear polyhedrosis virus containing
      the coding and leader sequence for human CRP (designated AcMNPV-CRP). Synthesis
      and secretion of CRP were studied after infection of TN5B1-4 and Sf-9 cells with
      AcMNPV-CRP. Accumulation of CRP but not other proteins in the medium over the
      course of infection suggested that CRP was actively secreted. Analysis by gel
      filtration chromatography and by SDS-PAGE demonstrated an intact pentamer
      composed of subunits of the appropriate molecular mobility. The structural
      integrity of the recombinant protein was further established by the ability of
      the product to bind to phosphocholine in a calcium-dependent manner, a property
      which is restricted to the intact pentamer. Functional studies of complement
      activation, binding to mononuclear phagocytic cells, and reactivity with a panel
      of monoclonal antibodies were also consistent with structural and functional
      integrity of the recombinant molecule. Infection of Trichoplusia ni larvae with
      AcMNPV-CRP also resulted in the production of functional recombinant protein.
      This method has the advantage of producing larger amounts of protein at lower
      cost than tissue culture. An additional advantage is the ability to metabolically
      label CRP through feeding the larvae on an [35S]methionine-containing
      diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527930
TI  - Identification of pigment epithelium-derived factor in the interphotoreceptor
      matrix of bovine eyes.
AB  - Pigment epithelium-derived factor (PEDF) is a neurotrophic protein and a member
      of the serine protease inhibitor superfamily. Here we describe the identification
      of PEDF in bovine eyes and optimization of its purification from this natural
      source. We have developed a polyclonal antibody to recombinant human PEDF, Ab
      rPEDF, that immunoreacts in a specific, sensitive, and linear fashion with PEDF
      protein, and furthermore, blocks its neurotrophic activity. We show that Ab-rPEDF
      specifically recognizes a 49,500-M(r) polypeptide on Western transfers of a wash
      of the extracellular matrix between the retinal pigment epithelium and the neural
      retina-termed interphotoreceptor matrix (IPM). PEDF is present as approximately
      1% of total soluble IPM protein. Starting with an IPM wash, PEDF protein is
      purified 164-fold to near homogeneity by ammonium sulfate fractionation and
      cation-exchange chromatography, with a recovery of 47%. The highly purified
      protein has an apparent M(r) of 49,500 +/- 1,500 as assessed by SDS
      polyacrylamide gel electrophoresis, and a native pI of 7.0-7.7. It elutes as a
      single peak on gel-filtration chromatography with a retention time immediately
      behind that of ovalbumin (43,000 M(r)). N-glycosidase treatment indicates that
      each PEDF molecule has a 5% carbohydrate content attached to internal asparagine
      residue(s). Amino terminal sequence of the purified PEDF reveals removal of an
      amino-terminal peptide region for the mature protein. Purified PEDF has
      neurotrophic activity on human retinoblastoma cells, as previously observed for
      IPM. The neurotrophic activities of both PEDF and IPM are blocked by antiserum Ab
      rPEDF. Altogether, PEDF is present in the bovine IPM as a soluble, extracellular,
      monomeric glycoprotein that by itself confers neurotrophic activity to the IPM.
      Thus, native PEDF isolated and purified as described here should prove useful for
      biochemical studies as well as other approaches.

PMID- 8527931
TI  - Baculovirus expression and purification of rat 10-formyltetrahydrofolate
      dehydrogenase.
AB  - The liver cytosolic enzyme, 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH)
      (EC 1.5.1.6) catalyzes two reactions: the NADP(+)-dependent oxidation of 10
      formyltetrahydrofolate to tetrahydrofolate and CO2 and the NADP(+)-independent
      hydrolysis of 10-formyltetrahydrofolate to tetrahydrofolate and formate. It
      exists as a tetramer of 99-kDa subunits in rat liver. We expressed rat liver cDNA
      encoding 10-FTHFDH in insect cells using the pVL 1393 expression vector and
      MaxBac expression kit. Despite the absence of a leader peptide the recombinant 10
      FTHFDH was released from the cells to the culture medium during production in
      both Sf9 and High five cell lines. The enzyme released into the medium was no
      less than 80% of the total recombinant 10-FTHFDH. Both enzyme pools, from the
      medium and from cell extracts, displayed high activity. The maximum expression of
      10-FTHFDH was observed 72 h postinfection in High five cells and 96 h
      postinfection in Sf9 cells. High five cells revealed four times higher expression
      of the recombinant enzyme per milligram of total cell protein than Sf9 cells.
      Passage of the cell-free culture medium over an affinity column of 5
      formyltetrahydrofolate-Sepharose provided 10-FTHFDH that was more than 95% pure.
      Additional purification on a Mono Q column resulted in an homogenous preparation
      of the enzyme. Purified recombinant 10-FTHFDH displayed both dehydrogenase and
      hydrolase activities, similar to those of the rat liver enzyme, and the
      recombinant enzyme remained active at least 12 months when stored appropriately.
      These results show that 10-FTHFDH can be overexpressed as a functional enzyme in
      baculovirus-infected insect cells and purified in two steps by simple
      chromatographic procedures.

PMID- 8527932
TI  - Purification and identification of brain-derived neurotrophic factor from human
      serum.
AB  - Brain-derived neurotrophic factor (BDNF), a 27-kDa noncovalently linked homodimer
      with subunits of approximately 13.5 kDa as viewed by SDS-PAGE, is thought to be
      primarily produced in the central nervous system. We report here the isolation of
      BDNF from pooled normal human sera, using a two-step purification process
      followed by SDS-PAGE, transfer to a polyvinylidene difluoride membrane, and
      subsequent identification of the protein by sequence analysis of the appropriate
      band(s) from the membrane. The level of BDNF in pooled human sera was estimated
      to be approximately 15 ng/ml as determined by an enzyme-linked immunosorbant
      assay. The average for six individuals was 18.9 +/- 5.7 ng/ml. There is an
      approximately 200-fold increase in the levels of BDNF in serum relative to
      plasma. Results from experiments using differential centrifugation suggest that
      the source of this increase is due to release from platelets. The presence of
      high levels of BDNF in serum suggests a role for this neurotrophin either in
      nerve repair at sites of injured tissue or in nonneuronal functions.

PMID- 8527933
TI  - An efficient system for active bovine pancreatic ribonuclease expression in
      Escherichia coli.
AB  - Bovine pancreatic ribonuclease (RNase A) is a member of a homologous group of
      extensively studied proteins. It is a small, basic protein, containing 124 amino
      acid residues and four stabilizing disulfide bridges. Ribonuclease A catalyzes
      the hydrolysis of the phosphodiester bonds in ribonucleic acids. Since this
      degradation of RNA interferes with normal cell functions, the signal peptide of
      alkaline phosphatase (phoA, Escherichia coli) was cloned onto the gene coding for
      RNase A, directing the protein to the periplasm. Several expression systems have
      been evaluated which use T7, trc, or PR promoters to transcribe the RNase A gene.
      Also, variation in host strains was tested to optimize the protein yield. It was
      found that the PR system gave better expression than the two other systems. E.
      coli strain BL21 was shown to be the strain in which export to the periplasm was
      most effective and recombinant RNase A could be isolated from the periplasmic
      fraction of these cells. The system provides a stable yield of active recombinant
      bovine pancreatic RNase of about 45-50 mg/liter of cell culture.

PMID- 8527934
TI  - Production of soluble and active recombinant murine interleukin-2 in Escherichia
      coli: high level expression, Kil-induced release, and purification.
AB  - We describe the production of soluble murine interleukin-2 (mIL2) and its
      purification following regulated release in the growth medium of Escherichia
      coli. The system is based on the ability of the Kil protein of pMB9 to release
      periplasmic proteins into the growth medium. As the kil gene is under control of
      the strong, but well regulatable pL promoter, the kil bearing plasmid is stably
      maintained in the cell. mIL2, fused to the outer membrane protein A (OmpA) signal
      peptide, was secreted into the periplasm and subsequently released into the
      growth medium after induction of the kil gene. This strategy allows a quick and
      easy purification of the heterologous protein without using strong denaturants or
      detergents, yielding a native protein with a specific biological activity equal
      to the natural mIL2. The system permits the production of mIL2 at levels up to 16
      mg/liter. From a 12-liter fermentation, a final yield of about 30 mg of pure mIL2
      was obtained.

PMID- 8527935
TI  - High-level production from a baculovirus expression system and biochemical
      characterization of human GMP synthetase.
AB  - GMP synthetase, a key enzyme in the de novo synthesis of guanine nucleotides, is
      a potential target for immunosuppression and anticancer chemotherapy. In order to
      closely examine the catalytic mechanism and active-site topography of this
      enzyme, large amounts of pure protein are needed. Catalytically active human GMP
      synthetase was expressed in a baculovirus system. A high-level production system
      has been established from which the yield of pure protein is routinely more than
      50 mg/10 liters of cell culture. The recombinant enzyme was purified to
      homogeneity and characterized. Like native GMP synthetase, the recombinant enzyme
      was resolved into two forms by ion-exchange chromatography. The two forms are
      both monomers and they differ in their isoelectric points. There is no evidence
      that these forms are in equilibrium or interconvertible. Protein sequence
      analysis reveals that both forms are blocked at the amino-terminus and they are
      essentially identical in sequence. Since they can be produced by a cDNA with a
      single open reading frame, we believe that they represent post-translational
      modification variants. The recombinant GMP synthetase is not distinguishable from
      the native enzyme in terms of chromatographic profiles, subunit composition,
      molecular weight, and kinetic properties. The inhibition constants and the modes
      of inhibition toward decoyinine, a selective inhibitor of GMP synthetase, are
      also the same as the native enzyme. The high-level production of active enzyme is
      invaluable to the determination of the three-dimensional structure and the
      discovery of potent and selective drug candidates.

PMID- 8527936
TI  - Purification of major fimbrial proteins of Porphyromonas gingivalis.
AB  - Binding of Porphyromonas gingivalis to pellicle-coated teeth is mediated to a
      large extent by fimbrillin, a major structural subunit of fimbriae. A simple and
      efficient method for purifying the major fimbrial proteins from various strains
      of P. gingivalis was developed. The sonic extracts of crude fimbriae were
      prepared from P. gingivalis strains 2561, A7A1-28, EM-3, and 9-14K-1, which are
      representatives of different fimbrial groups. The crude fimbriae were
      precipitated from the extracts with 40% saturated ammonium sulfate. The dialyzed
      crude fimbriae were dissolved in 8 M guanidine HCl and loaded onto a Sepharose CL
      6B column equilibrated with 6 M guanidine HCl. The major fimbrial protein
      enriched fractions were obtained and further purified to homogeneity by
      repetitive gel filtration on the same column. The purity and intactness of the
      purified fimbrial proteins were ascertained by SDS-polyacrylamide gel
      electrophoresis followed by silver nitrate staining and immunoblot analysis using
      rabbit antisera raised against the purified fimbrial proteins. The result
      demonstrates the usefulness of guanidine HCl as a reliable reagent for purifying
      various fimbrial proteins of P. gingivalis, which are often associated strongly
      with other outer membrane proteins and show different physicochemical and
      antigenic characteristics.

PMID- 8527937
TI  - The bovine photoreceptor outer segment guanylate cyclase: purification, kinetic
      properties, and molecular size.
AB  - A simple protocol was developed to isolate the integral membrane guanylate
      cyclase from bleached bovine photoreceptor outer segments. Hypotonic and
      hypertonic washes strip the photoreceptor outer segment membranes of peripheral
      proteins. The guanylate cyclase activity is solubilized by dodecyl-b-D-maltoside
      in a low salt concentration buffer. Phosphatidylcholine, glycerol, and
      dithiothreitol are used to stabilize the activity during chromatography. GTP
      affinity chromatography achieves a 250-fold increase in specific activity over
      that of membranes stripped of peripheral proteins. From 100 retinas, the protocol
      yields 100-140 mg of purified guanylate cyclase composed of a 115-kDa subunit.
      The molar ratio of the guanylate cyclase to rhodopsin is estimated to be 1:440. A
      significant portion of the freshly solubilized enzyme behaves as a monomer with a
      Stokes radius of 48.7 A, whereas the purified protein forms homooligomers ranging
      from dimers to tetramers. These properties are similar to those of ANP and
      guanylin receptors, indicating that the photoreceptor protein shares
      characteristics of the membrane receptor guanylate cyclase family. For the
      physiological substrate MgGTP, the Km and Vmax are 1.07 +/- 0.20 mM and 3262 +/-
      514 nmol cGMP min-1 mg-1, respectively, generating a turnover rate of
      approximately 3.9 nmol cGMP s-1 at physiological substrate concentrations. The
      relatively high Km suggests that in vivo changes in GTP concentration might
      modulate the rate of cGMP synthesis. These properties indicate that the
      photoreceptor membrane guanylate cyclase can sustain a rate of cGMP synthesis
      comparable to the dark-adapted (basal) rate of cGMP degradation by the cGMP
      phosphodiesterase.

PMID- 8527938
TI  - Large-scale production of HIV-1 protease from Escherichia coli using selective
      extraction and membrane fractionation.
AB  - Human immunodeficiency virus type 1 (HIV-1) protease was expressed in Escherichia
      coli as a fusion protein with the N-terminal sequence of IGF-2. The protein
      accumulated in inclusion bodies as a 40:60 mixture of unprocessed fusion protein
      and processed protein. A simple purification procedure was developed that yielded
      30-40 mg of active protease per liter of fermentation broth with a recovery of 30
      40%. The purification process involved the selective extraction of HIV-1 protease
      from E. coli inclusion bodies with 50% acetic acid and fractional diafiltration
      to remove impurities and low-molecular-weight protease-related fragments. No
      chromatographic steps were employed, yet the HIV-1 protease produced by this
      procedure was greater than 95% pure by SDS-PAGE, reverse-phase HPLC, and N
      terminal sequence analysis.

PMID- 8527939
TI  - Purification and renaturation of Japanese encephalitis virus nonstructural
      glycoprotein NS1 overproduced by insect cells.
AB  - The nonstructural protein NS1 of Japanese encephalitis virus is a major immunogen
      produced during flavivirus infection. However, the function of this protein has
      not been identified. To analyze its biochemical properties and evaluate its
      potential activity in the virus life cycle, the protein was produced in
      Spodoptera frugiperda insect cells (Sf9), using a recombinant baculovirus, and
      purified. As described previously by M. Flamand, V. Deubel, and M. Girard (1992,
      Virology 191, 826-836), a small fraction of the synthesized recombinant protein
      could mature into a dimer, whereas the major part was retained in intracellular
      aggregates. This insolubility was used to recover the protein in a purified form
      using a two-step procedure. Isolated inclusion bodies, in which NS1 constituted
      over 60% of the protein, were solubilized in 8 M urea. NS1 was further purified
      by reverse-phase HPLC and recovered at over 90% purity with an overall yield of
      over 60%. Conditions promoting reoxidation-renaturation of the purified protein
      were then investigated at a concentration of 100 micrograms/ml at pH 8. The
      presence of 8 M urea during reoxidation of NS1 with oxidized glutathione was
      essential prior to renaturation by dialysis to avoid reaggregation, the main side
      pathway of refolding in vitro. Three major species, all monomeric, were resolved
      by nonreducing SDS-PAGE. The form showing the lowest apparent molecular weight
      comigrated with native unreduced NS1 and was recognized by a monoclonal antibody
      directed against a conformational epitope strictly dependent on the native
      structure of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8527940
TI  - Affinity purification of ribulose-1,5-bisphosphate carboxylase/oxygenase large
      subunit epsilon N-methyltransferase.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit epsilon N
      methyltransferase (Protein methylase III, Rubisco LSMT, EC 2.1.1.43) catalyzes
      methylation of the epsilon-amino group of Lys-14 in the large subunit of Rubisco.
      In this paper, an affinity purification procedure for pea (Pisum sativum L. cv
      Laxton's Progress No. 9) Rubisco LSMT is described and characterized. Spinach
      (Spinacia oleracea L. cv Melody) Rubisco, a substrate for pea Rubisco LSMT, was
      immobilized to polyvinylidene fluoride (PVDF) transfer membranes (Immobilon-P)
      and used as a ligand for the affinity purification of Rubisco LSMT from pea leaf
      extracts and chloroplast lysates. Pea Rubisco LSMT specifically bound to PVDF
      immobilized spinach Rubisco but not to control PVDF membranes which contained
      immobilized BSA or pea Rubisco. Rubisco LSMT was not eluted by 1 M KCl but was
      specifically released by S-adenosyl-L-methionine (AdoMet) or spinach Rubisco.
      Elution of Rubisco LSMT by AdoMet was a result of catalytic methylation of the
      PVDF-immobilized spinach Rubisco, and was therefore more efficient than elution
      by the competitive ligand spinach Rubisco. An increase in the specific activity
      of Rubisco LSMT of approximately 7000-fold was achieved in one step with this
      affinity purification technique. Rubisco LSMT is a monomeric protein with a
      molecular mass of approximately 60 kDa.

PMID- 8527941
TI  - Multicopy overexpression of bovine pancreatic trypsin inhibitor saturates the
      protein folding and secretory capacity of Saccharomyces cerevisiae.
AB  - Bovine pancreatic trypsin inhibitor (BPTI) was expressed and secreted from a
      synthetic gene as a model system for the study of protein folding and secretion
      in Saccharomyces cerevisiae. The efficiency of different leader sequences in
      directing BPTI secretion was examined, and up to 11 micrograms/ml of active BPTI
      was secreted. In some fusion constructs, inefficient proteolytic processing by
      Kex2p, Ste13p, and signal peptidase were observed immediately adjacent to the
      BPTI N terminus. Insertion of dipeptide spacers improved endoproteolytic
      processing substantially but the level of secretion was unchanged. Overexpression
      from a 2-microns multicopy vector results in essentially unchanged BPTI secretion
      as compared to expression from a single copy centromere vector. BPTI expressed
      from a multicopy vector accumulates intracellularly in an unfolded form,
      indicating that available secretory chaperones and foldases can be saturated by
      increasing the rate of BPTI synthesis.

PMID- 8527942
TI  - Characterization of nuclear pore protein p62 produced using baculovirus.
AB  - Nuclear pore glycoproteins are essential components of the nuclear import
      apparatus in eukaryotes. In vertebrates, the most abundant of these glycoproteins
      is a molecule called p62. Like other O-linked N-acetylglucosamine glycoproteins,
      p62 is normally modified in the cytoplasm and cannot be overexpressed and
      conveniently collected in a secreted form. We devised an efficient scheme for
      expression and purification of recombinant p62 from Sf9 cells that may have
      general applicability for this class of glycoproteins. The purified rat p62 bound
      to wheat germ agglutinin, consistent with modification by O-linked N
      acetylglucosamine. Carbohydrate analysis, in conjunction with amino acid
      analysis, revealed that baculovirus-expressed rat p62 contains 5-6 mol of N
      acetylglucosamine/mol of p62. As observed by circular dichroism, purified p62
      expressed in the baculovirus system or in Escherichia coli share essentially the
      same secondary structure. Purified glycosylated rat p62 will be critical in
      determining the role of N-acetylglucosamine in both nuclear transport and
      assembly of the nuclear pore complex.

PMID- 8527943
TI  - Rapid purification of recombinant green fluorescent protein using the hydrophobic
      properties of an HPLC size-exclusion column.
AB  - The green fluorescent protein (GFP) of the jelly fish Aequoria victoria was
      cloned into an Escherichia coli cell line that is a methionine auxotroph. The
      recombinant GFP (rGFP) was isolated from the cells and purified using a simple
      procedure consisting of only two chromatographic steps: size-exclusion
      chromatography and ion-exchange HPLC. Due to the hydrophobic nature of the
      protein, the surface characteristics of the HPLC size column, and the high
      initial salt concentration, the rGFP sticks to the size column and is eluted by
      reducing the salt concentration. Due to this unique behavior the purification
      procedure can readily be scaled to handle larger quantities of rGFP.

PMID- 8527944
TI  - The peer review system--still no alternative in sight.

PMID- 8527945
TI  - Murine systemic autoimmune disease induced by mercuric chloride: T helper cells
      reacting to self proteins.
AB  - HgCl2 induces a CD4+ T-cell-dependent systemic autoimmune disease in susceptible
      strains of rats and mice. In rats, autoreactive T cells were shown to be
      involved, whereas in mice, attention has focussed on the demonstration of 'Hg
      specific' T cells. To clarify these seemingly different T cell involvements, T
      cells from B10.S mice treated with HgCl2 for 1 or 8 weeks were analyzed for their
      capacity to mount anamnestic responses against various self antigens (Ags) which
      either contained Hg or did not. T cells from donors short-term treated with HgCl2
      failed to mount memory responses to Hg-free Ags, but mounted a significant
      response to HgCl2 and also reacted with Hg-containing self Ags. Interestingly, T
      cells from donors long-term treated with HgCl2 showed a different pattern of
      reactivity. They hardly reacted to HgCl2 and reacted poorly to Hg-containing
      splenic proteins, but responded vigorously to nuclei and fibrillarin irrespective
      of whether these self constituents had been treated with HgCl2 or not.
      Conceivably, the initial activation of T cells that recognize Hg in combination
      with nuclear self proteins, such as fibrillarin, eventually results in activation
      of T cells specific for the unaltered self proteins.

PMID- 8527946
TI  - Decrease in systemic tolerance to fed ovalbumin in indomethacin-treated mice.
AB  - The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to
      animals induces a quick increase in intestinal permeability and secondary
      inflammatory lesions of the intestine. The mechanisms leading to the inflammatory
      lesions are hypothetical. The increased intestinal permeability could allow a
      greater mucosal and systemic penetration of fed antigens and bacterial products
      leading to an abnormal mucosal and systemic immune and inflammatory response
      toward these materials. We examined the effect of oral dosing with indomethacin
      on ovalbumin serum levels and the systemic immune response to ovalbumin in mice
      fed with ovalbumin. The ovalbumin serum level was higher in indomethacin-treated
      mice and the increase was proportional to the dose of indomethacin. It was
      associated with epithelial and subepithelial lesions. Moreover, the systemic
      humoral and, to a lesser extent, the cellular tolerance were partially abrogated
      in the treated mice. These findings suggest that the oral administration of
      indomethacin in mice induces an increased passage of fed antigen through the
      intestinal epithelium associated with a decrease in systemic tolerance to this
      antigen. The reason for this decrease remains unclear. Besides a disequilibrium
      between systemic and mucosal immune responses, a loss of integrity of the
      intestinal epithelial cells and a direct immunomodulating effect of indomethacin
      may also be involved. This decrease in systemic tolerance to luminal antigen
      could be involved in the development of NSAID enteropathy.

PMID- 8527947
TI  - Signal transduction by IgG receptors induces calcium mobilization, but not
      histamine release, in the human basophilic cell line KU812F.
AB  - Human blood basophils selectively express Fc gamma RII (CDw32) among IgG receptor
      subtypes, but its functional role in allergic reactions remains unknown. Using
      the human basophilic leukemia cell line KU812F as a model system, we investigated
      cellular signaling events mediated through IgG receptor stimulation. KU812F cells
      express Fc gamma RII on their surface. mRNAs for both Fc gamma RIIA and IIB
      subtypes were detected by reverse transcriptase-PCR analysis. In this cell line,
      Fc gamma RII stimulation induced mobilization of free intracellular calcium and
      actin polymerization. Yet, no significant histamine release was observed, nor did
      blood basophils stimulated by anti-Fc gamma RII monoclonal antibody IV.3 and by a
      secondary antibody release histamine. These data indicate that Fc gamma RII
      stimulation induces cellular signaling events such as calcium mobilization in
      human basophils. However, these events do not lead to histamine release.

PMID- 8527948
TI  - Immunology of human helminth infection.
AB  - Parasitic helminths cause enormous morbidity among humans especially in
      developing countries. These large extracellular organisms have complex life
      cycles frequently involving an arthropod vector. Helminth parasites can be tissue
      dwelling or intestinal but all induce a dramatic expansion of the Th2 lymphocyte
      subset. It remains unclear whether these Th2-derived responses, including IgE,
      eosinophilia and mastocytosis are important in the protective immune response to
      the parasite, or are responsible for immune-mediated pathology, or both.
      Interestingly, despite high levels of IgE and other features of Th2 cell
      activation, allergic responses are rarely observed in infected individuals.
      Helminths can survive for years in the infected host, and have evolved elaborate
      immune evasion strategies to establish these long-lived infections including the
      induction of tolerance to parasite antigens. This review discusses the dynamics
      of infection with helminth parasites with specific emphasis on Th2 subset
      activation. The current knowledge of immune effector mechanisms, immunopathology
      and hopes for vaccine development are also discussed.

PMID- 8527949
TI  - Antibody response in bronchoalveolar lavage and serum of rats after aerosol
      immunization of the airways with a well-adhering and a poorly adhering strain of
      Streptococcus pneumoniae.
AB  - This study describes the antibody response to two bacterial antigens, pneumolysin
      toxoid (PL) and purified pneumococcal capsular polysaccharide (PPS) 19F, in
      bronchoalveolar lavage (BAL) and in serum in rats after aerosol immunization with
      whole killed Streptococcus pneumoniae. To study the importance of bacterial
      adherence for antibody formation, one well-adhering and one poorly adhering
      strain of S. pneumoniae was used. The results show local specific anti-PPS 19F
      IgA, IgM and IgG antibody activities after aerosol immunization. Anti-PL antibody
      activity in all three immunoglobulin classes was found, although the anti-PL
      activity was lower than the anti-PPS 19F antibody activity. The IgA anti-PPS 19F
      antibody activity in BAL after immunization with the well-adhering strain was
      higher than with the poorly adhering strain. We conclude that aerosol
      immunization with S. pneumoniae induces a local, specific antibody production in
      the lung of the rat.

PMID- 8527950
TI  - Defective 'gut processing' of gliadin in mice with graft-versus-host enteropathy.
AB  - The gut mucosa plays an important role in the induction of oral tolerance.
      Extending previous observations, we have here shown that serum containing gut
      absorbed gliadin induces suppression of the specific systemic immune response in
      recipient mice parenterally immunized with gliadin. Graft-versus-host reaction
      (GvHR) has profound effects on the gut mucosa, representing a model of immune
      mediated enteropathy. The aim of our work was to investigate the gut handling and
      processing of gliadin in mice with GvHR. Binding to enterocytes, passage through
      the epithelium, and ability of the epithelium to convert this antigen into a
      tolerogenic form were assessed in BDF1 mice weaned on gluten-free diet, 2 weeks
      after the induction of a semiallogeneic GvHR. Binding of gliadin peptide B3144 to
      enterocytes was similar in controls and GvHR mice. After feed, serum levels of
      gliadin were comparable in the two groups of mice, but when serum collected from
      GvHR mice and containing gut-absorbed gliadin was transferred intraperitoneally
      into naive recipient mice, this did not induce suppression of the specific immune
      response. These experiments indicate that during GvHR enteropathy the ability of
      the intestine to convert gliadin into a tolerogenic form is lost. Defective
      antigen gut processing may contribute to the observed failure in oral tolerance
      induction.

PMID- 8527951
TI  - Identification of IgE-binding egg white proteins: comparison of results obtained
      by different methods.
AB  - The binding of IgE to egg white proteins was investigated for 34 sera from adults
      with a positive case history and/or positive RAST towards egg, and the impact of
      experimental conditions on IgE binding in commonly used methods was studied.
      Radioimmunoblotting after SDS-PAGE of both reduced and unreduced egg white
      extracts showed complex reaction patterns. The results were confirmed by crossed
      radioimmunoelectrophoresis (CRIE). Radio dot immunobinding was used to
      investigate the effect of treatment of allergens for SDS-PAGE and to evaluate the
      other methods. As a conclusion, the use of combinations of at least two methods
      is recommended for the identification of IgE-binding egg white proteins. Of the
      34 sera, 18 reacted with ovotransferrin, 13 with ovomucoid, 11 with ovalbumin and
      5 with lysozyme. The amounts of IgE bound to ovalbumin and lysozyme were
      generally lower than the amounts bound to ovotransferrin and ovomucoid.

PMID- 8527952
TI  - A two-dimensional electrophoretic analysis of latex peptides reacting with IgE
      and IgG antibodies from patients with latex allergy.
AB  - Latex proteins from nonammoniated natural rubber latex were investigated for
      their reactivity with antibodies in the sera of patients with spina bifida and
      health care workers with allergy to latex. Immunoblots of two-dimensional
      electrophoresis were used to compare the reactivity of various polypeptides
      against IgE, IgG, and subclasses of IgG. A total of 79 polypeptides showed
      reactivity with IgG and IgE antibodies from different patients. IgG showed
      reactivity with all the 79 polypeptides, while IgE reacted with 56 allergens.
      IgG2 reacted with the least number of proteins, while IgG4 reacted with the
      largest number of polypeptides. Several antigens were identified as significant
      due to their reactivity with antibodies in latex-allergic patients. Four proteins
      reacted with IgE, IgG1, IgG3 and IgG4 of only spina bifida patients with latex
      allergy, while one other protein reacted only with health care workers. Thus,
      these relevant latex peptides may be isolated, purified, and used in various
      assays for more reliable diagnosis of latex allergy.

PMID- 8527953
TI  - Quality of housing and allergy to cockroaches in the Dominican Republic.
AB  - Fifty-one atopic asthmatic and/or allergic rhinitic children and 23 nonatopic
      control from Santo Domingo, the Dominican Republic, were skin tested with an
      extract mix of three cockroach species (Blattella germanica, Blatta orientalis,
      and Periplaneta americana). Sixteen percent of the atopics and none of the
      nonatopics demonstrated positive immediate skin reactions to the cockroach mix
      (chi 2 = 4.05, p = 0.04). Hypersensitivity was correlated with the quality of the
      homes; 22% (8/36) of the atopics who lived in a concrete home were skin test
      positive to the cockroach mix, while none (0/15) of the atopics who lived in a
      wood home were skin test positive (chi 2 = 4.86, p = 0.03). Although the
      incidence of cockroach allergy in this study is lower than that found elsewhere,
      these data support the notion that, in this tropical environment, sensitization
      to cockroaches is associated with housing quality.

PMID- 8527954
TI  - Cytokine concentrations in sputum of asthmatic patients.
AB  - To examine whether levels of inflammatory cytokines and eosinophil cationic
      protein (ECP) in the sputum reflect the severity of bronchial asthma, we measured
      their levels in the sputum of symptomatic and asymptomatic asthmatics.
      Interleukin (IL)-1 beta, IL-5, IL-6, IL-8, RANTES, tumor necrosis factor-alpha
      and ECP concentrations in the sputum of symptomatic patients were significantly
      higher than in asymptomatic subjects. These findings suggest that these
      inflammatory cytokines are involved in the exacerbation of asthma.

PMID- 8527955
TI  - Effects of a thromboxane synthase inhibitor (CS-518) on the eosinophil-dependent
      late asthmatic response and airway hyperresponsiveness in guinea pigs.
AB  - The effects of CS-518, a thromboxane A2 synthase inhibitor, on antigen-induced
      dual bronchial responses, airway hyperresponsiveness (AHR) and airway
      eosinophilia were investigated in an experimental guinea pig model of the late
      asthmatic response. Oral CS-518 (1 and 10 mg/kg) inhibited immediate and late
      asthmatic responses dose-dependently. It also inhibited AHR and eosinophil
      accumulation after antigen challenge. Therefore, thromboxane A2 is possibly
      involved in development of the late asthmatic response and AHR, and CS-518 was
      inferred to inhibit these via inhibition of eosinophil accumulation and
      thromboxane production.

PMID- 8527956
TI  - Relationship between airway eosinophilia and airway hyperresponsiveness in a late
      asthmatic model of guinea pigs.
AB  - To elucidate the mechanism of development of asthma, we tried to develop a model
      which elicited a late asthmatic response by a combination of systemic and inhaled
      sensitization with ovalbumin in guinea pigs. Eighty-seven percent of animals
      elicited both an immediate and late asthmatic response after the third antigen
      inhalation. Airway eosinophilia and airway hyperresponsiveness (AHR) induced
      after the third challenge were more severe than those after the first challenge.
      There was a good correlation between airway eosinophilia and AHR in this model
      under experimental modulation of the number of eosinophils, such as by
      interleukin 5 or antieosinophil antibody injection. These results demonstrate
      that eosinophils play an important role in the development of late asthmatic
      response and AHR.

PMID- 8527957
TI  - Lipid clearing agents in steroid-induced osteoporosis.
AB  - Osteoporosis is a major complication of long-term steroid use. In this
      experimental study, the effect of lipid clearing agents on the preservation of
      bone mass was assessed. New Zealand white rabbits were divided into four groups:
      normal control, steroid only, steroid plus lovastatin and steroid plus
      bezafibrate. Treatments were continued for either 6 to 8 weeks or 13 to 15 weeks,
      after which the rabbits were sacrificed. Each rabbit's trabecular bone area from
      the central saggital sections of the femoral head was measured. At 6 to 8 weeks
      there was no significant difference between the steroid groups, but at 13 to 15
      weeks the bone area in the steroid only group was significantly lower than in the
      groups that had also received lipid clearing agents. Histologic examination of
      livers from the normal control group showed significantly less degeneration than
      in all of the steroid groups. Lipid clearing agents appear to maintain bone mass
      in the femoral head, but do not avert fatty changes in the liver in steroid
      treated rabbits. Concomitant use of lipid clearing agents with steroids may have
      the potential to decrease the severity of steroid induced osteoporosis.

PMID- 8527958
TI  - Effects of L-glutamine on induced hepatosteatosis in rats receiving total
      parenteral nutrition.
AB  - Glutamine (Gln) supplementation in total parenteral nutrition (TPN) has been
      shown to have a preventive effect on high glucose induced hepatic steatosis. This
      animal study was undertaken to evaluate whether Gln could prevent hepatic
      steatosis induced by high fat or high glucose infusion. After placement of
      internal jugular catheters, rats were divided into three groups: control (n = 8),
      high fat (n = 13) and high glucose (n = 14) groups. The control group was fed
      with a chow diet and infused with saline alone. The experimental groups were
      infused with either a high fat (65% of nonprotein calories) or high glucose (83%
      of total kilocalories) solution. Energy intake was 35 kcal/100 g body weight per
      day. TPN solutions were isocaloric, isonitrogenous and isovolemic. Each
      experimental group was divided into two subgroups, with one receiving a Gln
      supplement to replace 40% of total amino acid nitrogen. The results demonstrated
      obvious fatty infiltration in the experimental groups, mainly from triglyceride
      (TG) accumulation. Plasma very low density lipoprotein-triglyceride (VLDL-TG) was
      significantly lower in the experimental groups than in the control group,
      suggesting that liver secretion of TG may have been inhibited in the experimental
      groups. Liver fatty acid synthetase (FAS) activity and plasma free fatty acid
      were lower in the high fat group than in the control and high glucose groups.
      There was no difference in hepatic lipids content, FAS activity, VLDL-TG, hepatic
      uptake of fatty acids and liver histologic change in the subgroups with and
      without Gln supplementation. Thus, Gln supplementation in a TPN solution has no
      effect in preventing hepatic steatosis induced by either high glucose or high fat
      infusion in rats under these experimental conditions.

PMID- 8527959
TI  - Heterotopic pregnancies after controlled ovarian hyperstimulation and assisted
      reproductive techniques.
AB  - Eight cases of heterotopic pregnancy following assisted reproductive techniques
      (ART) were reviewed. One cervical, three cornual and four tubal pregnancies were
      combined with intrauterine pregnancies. The cervical ectopy was successfully
      treated with a local injection of potassium chloride (KCl) into the gestational
      sac. A viable baby was produced from the intrauterine gestation. Cornual
      metroplasties were performed on two ruptured and one unruptured cornual
      heterotopic pregnancies. One of these three cases was maintained till term. All
      four tubal heterotopic pregnancies were aborted. Widespread application of ART in
      recent years has meant that heterotopic pregnancies are no longer a rarity. Both
      physicians and patients should be made aware that the existence of an
      intrauterine gestation does not preclude the risk of nidation of other fetuses in
      ectopic sites. The authors recommend that detailed ultrasound studies, preferably
      via the vaginal route, should be performed on patients in ART programs. During
      the examination, the adnexae should be carefully evaluated, even if an
      intrauterine gestational sac is already present. If a heterotopic pregnancy is
      diagnosed, the appropriate treatment depends on the location of ectopic
      pregnancy. Local injection with KCl or methotrexate is effective in certain types
      of cervical or cornual ectopic pregnancy, as it may allow the conservation of the
      intrauterine pregnancy.

PMID- 8527960
TI  - MRI of meniscus and cruciate ligament tears correlated with arthroscopy.
AB  - Findings from magnetic resonance imaging (MRI) studies of 50 knees were
      retrospectively interpreted. The results were correlated with arthroscopic
      findings. Multiple pulse sequences were performed including sagittal double-echo,
      coronal T1-weighted and gradient echo, axial gradient echo or fat suppression
      imaging. Three-dimensional MRI was performed if there was a high suspicion of a
      tear of the anterior cruciate ligament. The individual positive predictive value,
      sensitivity, specificity and accuracy were calculated from the comparison between
      MRI and arthroscopic findings of the menisci, anterior cruciate ligament and
      posterior cruciate ligament. The following results were obtained: 1) Tears of the
      medial meniscus-positive predictive value, 72%; sensitivity, 87%; specificity,
      86%; and accuracy, 86%. 2) Tears of the lateral meniscus-positive predictive
      value, 85%; sensitivity, 85%; specificity, 90%; and accuracy, 88%. 3) Tears of
      the anterior cruciate ligament-positive predictive value, 88%; sensitivity, 95%;
      specificity, 89%; and accuracy, 92%. 4) Tears of the posterior cruciate ligament
      positive predictive value, 100%; sensitivity, 100%; specificity, 100%; and
      accuracy, 100%. It is concluded that MRI is a noninvasive and accurate method for
      detecting the internal derangement of the knee.

PMID- 8527961
TI  - Allogeneic peripheral blood progenitor cell transplant after bone marrow graft
      failure: report of a case.
AB  - A 31-year-old woman diagnosed with acute myelocytic leukemia received an
      allogeneic peripheral blood progenitor cell (PBPC) transplant one month after a
      previous bone marrow graft failed. PBPCs were mobilized with granulocyte-colony
      stimulating factor and collected by apheresis. T-cell depletion was not performed
      and no further chemo- or radiotherapy was given for the second transplant.
      Engraftment was prompt, with the peripheral blood leukocyte count rising
      dramatically to 2,400/microL, six days after completion of PBPC transplant. The
      platelet count reached 36,000/microL on the eighth day and was self-sustained
      thereafter. Both blood grouping and bone marrow karyotyping confirmed donor
      origin of the engraftment. At the time of writing, the patient has been disease
      free for over 200 days without any complications of acute or chronic graft-versus
      host disease.

PMID- 8527962
TI  - Secondary dentin deposition in dens evaginatus: report of a case.
AB  - An unusual case of dens evaginatus in a 22-year-old man is reported. The involved
      tooth was the right upper second premolar which appeared to have been segregated
      into coronal and apical segments during the disease process. Although abscess
      formation was noted in the coronal portion, continuing secondary dentin
      deposition was found over the displaced apical segment. The pathogenesis of this
      unusual dentinal bridge formation is proposed based on the microscopic and
      radiographic findings.

PMID- 8527963
TI  - Prenatal diagnosis of tetralogy of fallot by Doppler color flow mapping.
AB  - The prenatal diagnosis of tetralogy of Fallot (TOF) can be difficult, as the
      routine sonographic four-chamber view may be normal before birth. Unlike the
      normal fetus, in which blood flows adjacent to the left side of the
      interventricular septum, on color Doppler mapping a fetus with TOF also
      demonstrates antegrade flow along the right side of the interventricular septum.
      This Y-shaped ventricular outflow passing through the dilated aortic tract is
      confluent at the level of the ventricular septal defect during the systolic
      phase. In the past 3 years, three cases of TOF have been diagnosed prenatally at
      the Chang Gung Memorial Hospital. In each case, the above picture was
      demonstrated. 2-Dimensional Doppler color flow mapping may be helpful in the
      prenatal diagnosis of TOF.

PMID- 8527964
TI  - Prevalence of goiters in children residing in Tung-Lo Township, Taiwan.
AB  - This study investigated school children in the Tung-Lo Township in central Taiwan
      to determine the prevalence of goiters compared to other areas of Taiwan and to
      elucidate the possible etiology. All children attending elementary schools in
      Tung-Lo were examined for thyroid enlargement by neck palpation, as recommended
      by the World Health Organization. Thyroid antibodies and thyroid hormones were
      determined in children with goiters, and in normal age- and sex-matched controls.
      Additionally, analysis of drinking water for humic substances was done by
      fluorospectrophotometry. In total, 1,823 school children were examined (965 boys
      and 858 girls). Of these, 174 (9.5%) were found to have a goiter of grade I or
      above. The prevalence was higher than our recent surveys in other areas of Taiwan
      (2.6%-8.8%). Goiter prevalence in school children residing in hill regions
      (12.9%), mainly dependent on underground water for drinking, was higher than that
      of school children residing in plain regions (8.2%), who depend on tap water for
      drinking. The quality of drinking water bore a close relationship to the
      prevalence of goiter. From the ratio of T3/T4 in this study, and a study of
      urinary iodine excretion done by others, it is concluded that goiters in Tung-Lo
      are not related to iodine deficiency. There was no statistically significant
      correlation between the relative fluorescence intensity of humic substances and
      the prevalence of goiter. The results of this study suggest that the higher
      prevalence of goiter in children living in Tung-Lo, an oil-bearing area, may be
      related to the quality of drinking water.

PMID- 8527965
TI  - Predictive value of endometrial sonography in ovulation induction for
      intrauterine insemination.
AB  - This prospective study was undertaken to evaluate the prognostic value of the
      endometrial sonographic pattern on the day of human chorionic gonadotropin (hCG)
      administration in patients who underwent intrauterine insemination. The
      endometrial sonographic patterns were classified as homogenous, hyperechogenic
      (A), intermediate isoechogenic (B) and multiple-layered "triple-line" (C). Type A
      had no pregnancies, whereas type B had a 20% fecundity rate and type C had a
      21.1% fecundity rate. The continuing pregnancy rate was 10% in type B, as
      compared to 19.3% in type C. The data suggest that the endometrial sonographic
      pattern on the day of hCG administration may be of predictive value regarding
      fecundity and continuing pregnancy in the intrauterine insemination cycle.

PMID- 8527966
TI  - Pacemaker twiddler's syndrome: report of a case.
AB  - A patient with symptomatic atrioventricular blockage who had been treated by
      permanent pacemaker implantation, developed twiddler's syndrome 16 days after
      implantation. The electrode lead to the pacemaker pocket had been completely
      displaced, with the electrode tip having moved to the outside of the subclavian
      vein. Complete atrioventricular block was demonstrated by electrocardiogram.
      Reimplantation of the same electrode at the apex of the right ventricle relieved
      the symptoms. The patient is regularly followed up at an outpatient clinic and
      continues to be well. Although twiddler's syndrome is a rare complication of
      pacemaker implantation, preventive measures should be undertaken especially for
      those judged to be at high risk.

PMID- 8527967
TI  - Pseudomelanosis duodeni: report of eight cases.
AB  - Pseudomelanosis duodeni is an uncommon endoscopic sign characterized by diffuse
      small black spots on the first and second portions of the duodenum. It occurs
      predominantly in female and elderly patients and is linked to chronic illnesses
      and related medications. Between 1988 and 1994, the authors saw eight patients
      with pseudomelanosis duodeni. To evaluate the nature of the pigments, special
      staining was performed in seven cases. Iron stain was strongly positive in three
      cases. Electron microscopy was performed in two cases. This revealed amorphous
      bodies within macrophage lysosomes in one case and angular crystals in another
      case. These tests suggest that in pseudomelanosis duodeni iron metabolism may be
      impaired and iron is pooled within macrophages.

PMID- 8527968
TI  - Percutaneous endoscopic gastrostomy in infants.
AB  - After a trial of 1 month of nasogastric tube feeding, three infants (aged 5-14
      mo) underwent percutaneous endoscopic gastrostomy (PEG) to enable long-term
      enteral feeding. The Ponsky-pull technique was employed for PEG insertion. In two
      patients, the procedure was complicated by superficial wound infection at the
      cutaneous exists of the PEG tubes: one with Pseudomonas sp and the other
      staphylococcal colonization. Both responded well to antibiotic treatment. All
      patients obtained good nutritional support. The preliminary experience reported
      here suggests that, even in infants, PEG is a safe and easy nonsurgical method of
      enteral feeding.

PMID- 8527969
TI  - Computed tomography and magnetic resonance imaging of diffuse pigmented
      villonodular synovitis: report of a case.
AB  - We describe the computed tomographic (CT) and magnetic resonance imaging (MRI)
      features of a surgically proven case of diffuse pigmented villonodular synovitis
      (PVNS) of the knee in a 34-year-old woman. A complex mass consisting of solid and
      multicystic components was clearly demonstrated by CT and MRI. The solid part
      showed homogeneous hypodense attenuation relative to adjacent muscles on CT
      scans, but it showed inhomogeneous signal intensity on spin echo T1- and T2
      weighted images (WI). The solid component enhanced homogeneously on CT scans but
      heterogeneously on MR images. Multiseptated enhancement of the cystic component
      on both CT and MR images were displayed. All of the above features were better
      demonstrated on MRI. Multiple marked hypointense round and patchy areas, and also
      a few areas isointense to subcutaneous fat within the lesion were also found on
      T1WI, proton density WI and T2WI. These characteristic MRI features of PVNS
      correlated well with its histologic structures: depositions of hemosiderin and
      fat in the proliferative synovial villi and bloody cystic content. These features
      may help to distinguish PVNS from other disease entities arising from the
      synovium.

PMID- 8527970
TI  - Delayed transhemispheric c-fos gene expression after focal cerebral ischemia
      reperfusion in rats.
AB  - Using a unilateral, focal, cortical, ischemia-reperfusion rat model, c-fos mRNA
      and Fos immunoreactivity in the brain were investigated. The study was divided
      into a series of reperfusion intervals which were carried out for a period of up
      to 7 days. The c-fos mRNA peaked in the ischemic cortex (about 15-fold) after 30
      minutes of ischemia followed by 1 hour of reperfusion and dropped to baseline
      level after 1 day of reperfusion. Increased expression switched to the bilateral
      retrosplenial and frontal cortex, as well as the left (nonischemic) parietal
      cortex, at 3- or 5-days of reperfusion (about three- to fourfold). Fos
      immunohistochemical staining correlated positively with the surge of c-fos mRNA.
      Nuclear run-off transcription assays further indicated that the increase in c-fos
      mRNA was regulated at the transcriptional level not only in the ischemic cortex
      (30 min of ischemia, followed by 1 h of reperfusion) but also in the
      contralateral counterpart (30 min of ischemia, followed by 3 d of reperfusion). A
      link between altered gene expression and diaschisis is suggested. The
      distant/delayed c-fos expression is probably caused by loss of inhibition from
      the ischemic cortex through a polysynaptic transneural pathway.

PMID- 8527971
TI  - Density of muscarinic receptors in rat myocardium during early sepsis.
AB  - The muscarinic receptor changes in two subcellular fractions of rat myocardium
      during sepsis, the sarcolemma (SL) and light vesicles (LV), were studied. [3H]
      quinuclidinyl benzilate ([3H]-QNB) was used as a radioligand. Sepsis was induced
      by cecal ligation and puncture (CLP). The septic rats had higher pulse rates and
      slightly higher blood glucose levels than control rats. The marker enzyme assays
      revealed that the SL fraction was enriched with 5'-nucleotidase and the Na(+)
      K(+)-ATPase activity increased over 20-fold, while the LV fraction showed very
      little enrichment when compared with the homogenate. [3H]-QNB binding studies
      showed that Bmax increased by 58.8% in SL with no changes in LV during early
      sepsis (9 h post-CLP), but there was no significant change in the Kd value. These
      data indicate that muscarinic cholinergic receptors in rat heart SL increase
      during early sepsis. Since the muscarinic cholinergic receptors mediate
      parasympathetic modulation of myocardial contractility, changes in the number of
      muscarinic receptors in the cardiac SL may have a pathophysiologic significance
      in the development of hemodynamic changes during sepsis.

PMID- 8527972
TI  - HER-2/neu overexpression in Chinese breast cancers: correlation with other
      prognostic factors.
AB  - HER-2/neu oncogene amplification or overexpression has generated considerable
      interest in predicting the outcome of breast cancer in Caucasians. In the present
      study, Northern blot analysis was used to investigate 44 primary breast cancers
      of different stages in Chinese patients. Nineteen tumors (43.2%) demonstrated
      more than two-fold expression of HER-2/neu mRNA over adjacent non-tumor breast
      tissue. The incidence of HER-2/neu overexpression in this series is higher than
      those reported in Caucasian studies. Ethnic variation is perhaps the only
      contributing factor. In node-negative patients, the incidence of HER-2/neu
      overexpression was also higher (33.3%), which could imply a worse prognosis in
      node-negative Chinese patients than in their Caucasian counterparts. A
      significant correlation between HER-2/neu overexpression and cancer stage was
      demonstrated. There were also trend relationships between HER-2/neu
      overexpression and other prognostic factors, including the number of positive
      axillary lymph nodes, tumor size, hormone receptor status and age at diagnosis,
      but none of these correlations were statistically significant. In axillary lymph
      node-negative patients, HER-2/neu overexpression was associated with estrogen
      receptor-negative status, a factor predicting worse outcome. These findings imply
      that HER-2/neu overexpression may identify a subgroup of node-negative patients
      with a poor prognosis who would otherwise have a favorable prognosis.

PMID- 8527973
TI  - Relationship between serum prostate specific antigen concentration and prostate
      volume.
AB  - Serum prostate-specific antigen (PSA) levels and prostate volume were evaluated
      in 553 healthy men aged 40 to 79 years, who entered a study program for benign
      prostatic hyperplasia from December 1993 to August 1994. Digital rectal
      examination (DRE), transrectal ultrasonography (TRUS) and serum PSA assay were
      performed on all participants. After excluding men with suspected prostate cancer
      and incomplete data, 542 cases qualified for analysis. The mean serum PSA level
      was 1.4 +/- 1.7 ng/mL which increased with age from 0.8 +/- 0.9 ng/mL in men aged
      40 to 49 years to 2.7 +/- 2.8 ng/mL in those aged 70 to 79 years. In this study
      group, 250 men (46.1%) were documented to have various degrees of benign
      prostatic hyperplasia (BPH). The prostate volume averaged 22.3 +/- 9.1 mL which
      increased from 18.5 +/- 6.1 mL in the fifth decade to 27.2 +/- 13.7 mL in the
      eighth decade. There was a modest correlation between serum PSA level and both
      age and prostate volume. However, when the prostate volume was adjusted, the PSA
      level correlated more weakly with age in a multivariate analysis. On the other
      hand, the serum PSA level correlated more strongly with prostate volume when age
      was adjusted. Although 5.4% of the men had serum PSA levels > 4 ng/mL, there was
      no evidence of prostate cancer by DRE and TRUS. Serum PSA levels increased with
      age and prostate volume, and correlated better with the latter. These factors
      should be taken into account when determining the significance of a given PSA
      value in a patient without clinical evidence of prostate cancer.

PMID- 8527974
TI  - Haloperidol plasma concentrations in Taiwanese psychiatric patients.
AB  - Haloperidol and reduced haloperidol are interconverted. The plasma concentrations
      of these two butyrophenones have been suggested to be important factors in
      determining the clinical effect of haloperidol treatment. The steady-state plasma
      concentrations of haloperidol and reduced haloperidol were measured in 322
      Taiwanese schizophrenic patients using high performance liquid chromatography.
      The daily doses of haloperidol varied from 5 to 200 mg (mean +/- SD, 35.3 +/-
      34.6 mg). There was a positive correlation between plasma concentrations and
      doses, following the equation: haloperidol concentration (ng/mL) = 0.88 x dose
      (mg/day)-1.66. However, the interpatient variation in haloperidol concentrations
      was up to ten-fold even in patients receiving the same dose (20 mg/day, n = 88).
      The expected values were about 10% to 50% higher than those reported in Caucasian
      patients. The plasma reduced haloperidol concentrations were significantly lower
      than, and correlated with, those of haloperidol in patients with haloperidol
      levels lower than 25 ng/mL. However, once haloperidol exceeded 25 ng/mL, reduced
      haloperidol levels rapidly elevated and appeared significantly higher than
      haloperidol levels. While haloperidol could reach its steady state in about 1
      week, reduced haloperidol needed at least 4 weeks to do so. Haloperidol doses of
      less than 30 mg/day and plasma concentrations lower than 25 ng/mL are recommended
      for most Chinese patients.

PMID- 8527975
TI  - Complete two-handed laparoscopic appendectomy: report of 100 cases.
AB  - A complete two-handed technique for laparoscopic appendectomy is described. From
      April 1992 to July 1994, 100 patients with suspected acute appendicitis were
      selected to undergo this approach. This technique allows the surgeon to
      manipulate instruments with both hands for dissecting, transecting and removing
      the appendix. The appropriate placement of three cannulas in the lower abdominal
      midline makes this technique possible. Monopolar cautery is used to dissect the
      mesoappendix and to cauterize the appendicular vessels. Two ligatures are placed
      at the junction of the appendix with the cecum. The appendix is clamped at its
      base by ratchet forceps and is extracted along with the forceps immediately after
      transection. None of the patients selected for this procedure required conversion
      to open appendectomy. Postoperative complications occurred in four patients, two
      with umbilical wound infections and two with intra-abdominal abscesses; 12
      patients had perforated appendicitis. The results of this study suggest that a
      complete two-handed laparoscopic appendectomy can be safely and successfully
      accomplished in patients with suspected acute appendicitis.

PMID- 8527976
TI  - Female genital tuberculosis: report of seven cases.
AB  - Seven cases of histologically proven genital tuberculosis (TB) encountered at the
      National Taiwan University Hospital in the past 16 years were reviewed. From a
      total of 54,576 gynecologic specimens submitted for pathologic examination, the
      occurrence of genital TB was 0.01%. Of these seven patients, one suffered from
      primary infertility and one from secondary infertility. The patient with primary
      infertility had been married for 29 years. The patient with secondary infertility
      underwent a tuboplasty due to bilateral hydrosalpinx. Genital TB was not
      diagnosed preoperatively in any of the seven cases. The preoperative diagnoses
      included: postmenopausal spotting, ovarian malignancy, cervicitis, ectopic
      pregnancy and hydrosalpinx with secondary infertility. This review suggests that
      genital TB is becoming rare in Taiwan. It is difficult to diagnose from clinical
      symptoms and is usually discovered on pathologic examination.

PMID- 8527977
TI  - Richter's syndrome: report of a case.
AB  - A 42-year-old male presented with generalized massive lymphadenopathy, fever,
      weight loss and numerous cutaneous nodules. Peripheral blood examination showed
      lymphocytosis with small lymphocytes, and immunophenotyping revealed B-cell
      chronic lymphocytic leukemia (CLL). Cytogenetic analysis of bone marrow aspirate
      revealed a clonal abnormality of chromosome 11. Lymph node biopsies showed a B
      immunoblastic lymphoma. A diagnosis of Richter's syndrome (RS) was made. The
      patient did not respond to doxorubicin, cyclophosphamide, vincristine and
      prednisolone (CHOP) and died of progressive disease with pneumonia and
      respiratory failure 9 months later. CLL is not common among Chinese people and RS
      is extremely rare.

PMID- 8527978
TI  - Severe aplastic anemia induced by ticlopidine: report of a case.
AB  - Ticlopidine is a powerful antiplatelet activator that inhibits adenosine
      diphosphate (ADP)-induced platelet aggregation. Its most common side-effects are
      skin rashes, diarrhea and neutropenia. Aplastic anemia is rare. This paper
      reports a patient with severe aplastic anemia that developed after the use of
      ticlopidine. The 85-year-old woman developed fever, chills and chest pain 5 weeks
      after starting ticlopidine 250 mg twice daily. Severe aplastic anemia was proved
      by blood examination, bone marrow aspiration and biopsy. In spite of the recovery
      of absolute neutrophil count to more than 1,000/mm3, 16 days after ticlopidine
      was stopped and administration of strong antibiotics, the patient died from
      candidal sepsis.

PMID- 8527979
TI  - Fibromuscular dysplasia associated with intracranial giant aneurysm: report of a
      case.
AB  - Although the correlation between fibromuscular dysplasia (FMD) and intracranial
      aneurysm is well established, the combination of FMD with a giant aneurysm is
      rare. This paper reports a patient with extracranial FMD associated with a giant
      intracavernous aneurysm compromising the trigeminal and abducens nerve. A review
      of the literature uncovered only four documented cases of FMD with concurrent
      giant intracranial aneurysms. The present case adds further weight to the
      argument for including FMD in the differential diagnosis list when confronted
      with a patient with a giant intracranial aneurysm. Absence of adequate
      collaterals in this patient eliminated ligation as a treatment strategy for the
      aneurysm.

PMID- 8527980
TI  - Stiff-man syndrome: report of a case.
AB  - A 40-year-old Taiwanese farmer developed progressive stiffness and pain in the
      lower back with intermittent cramps over a 3-year period. The cramps were
      extremely painful and the patient was sensitive to any sudden movement or
      external stimulation. His lower back was so stiff that the patient had great
      difficulty performing daily activities and walked with a rigid and straight back.
      The stiffness of the muscles subsided during normal sleep. Except for a left S1
      radiculopathy, no other neurologic abnormalities were noted. Electromyography
      showed spontaneous continuous muscle fiber activity which was markedly suppressed
      after a trial with 20 mg intravenous diazepam. The muscular stiffness disappeared
      during treatment with oral diazepam 80 mg daily, which was tapered to 15 mg daily
      without any recurrence of spasm for 20 months. This is the first report of stiff
      man syndrome in a Taiwanese patient and emphasizes the importance of recognizing
      this treatable disease.

PMID- 8527981
TI  - Insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in
      Taiwanese women during normal pregnancy.
AB  - Circulating levels of insulin-like growth factor-I (IGF-I) and insulin-like
      growth factor-binding protein-1 (IGFBP-1) in Taiwanese women during normal
      pregnancy were investigated. Three hundred and eighty-five pregnant women at
      various gestational ages and 30 nonpregnant females were recruited into the
      study. Serum concentrations of IGF-I and IGFBP-1 were determined by
      immunoradiometric assay (IRMA) and radioimmunoassay (RIA). Maternal serum levels
      of IGF-I increased as pregnancy progressed. Circulating IGF-I levels in women
      during the first trimester of pregnancy were higher than those in nonpregnant
      females. Serum levels of IGFBP-1 rose rapidly before 12 weeks of gestation and
      remained high until term. Serum IGFBP-1 levels in pregnant women during the first
      trimester were significantly higher than those in nonpregnant females. However,
      there was no difference in maternal serum IGFBP-1 levels between the second and
      the third trimester of pregnancy. It is concluded that serum IGF-I levels during
      pregnancy may be regulated by various classes of IGF-binding proteins other than
      IGFBP-1.

PMID- 8527982
TI  - Pneumatic reduction of intussusception in children.
AB  - Over the past decade, pneumatic reduction has been increasingly accepted as the
      treatment of choice for pediatric intussusception. However the effectiveness of
      air compared with the more traditional barium reduction of intussusception
      continues to be a source of concern and debate. From August 1993 to November
      1994, pneumatic reduction was used to treat 75 episodes in 73 patients with
      proven intussusception at Chang Gung Memorial Hospital, Taoyuan. Two patients
      underwent air reduction twice because of recurrence following an initial
      successful reduction. The recurrence rate was 3%. Successful reduction was
      achieved in 65/75 (87%) episodes. None of the patients experienced any
      complications following the procedure. In two of the 10 patients in whom
      reduction failed, one was subsequently found to have a Meckel's diverticulum and
      the other a duplication cyst as a leading point. This prospective study indicates
      that air enema is a safe and effective form of treatment for intussusception in
      infants and children. Pneumatic reduction should be the treatment of choice in
      the initial management of intussusception.

PMID- 8527983
TI  - [Multimeasurement analysis of the autonomic status in the development of stress
      in man].
AB  - A parallel investigation, an analysis of the clinical physiological study, and
      polymetrical description were made while examining 245 workers at an electronic
      plant. The findings allowed the author to identify four main classes in terms of
      the stages of stress development, to make clinical and physiological evaluation
      of the multivector spectra-pattern state during stress, to assess the autonomic
      status and to make an interactive syndromal analysis of a person's functional
      condition.

PMID- 8527984
TI  - [Physiological approaches to enhancing cardiac resistance in emotional stress].
AB  - The role of parasympathic effects, graded motor activity, positive emotions, and
      delta-sleep peptide in enhancing the resistance of cardiac performance in
      experimental emotional stress was studied in chronic rabbit experiments. The
      prevalence of parasympathic effects was demonstrated to increase cardiac electric
      stability and to prevent the elevation of catecholamine levels and the
      development of myocardial structural damages during stress. A moderate motor
      activity was found to lead to the session of ventricular extrasystole occurring
      in stress due to decreases in the myocardial levels of epinephrine with its high
      levels remaining in blood. Ventricular extrasystole also disappeared after
      activation of the positive emotional centers of the hypothalamus and after
      administration of delta-sleep peptide normalizing the electrical stability of the
      heart in emotional stress.

PMID- 8527985
TI  - [Conscious perception of a stimulus as a somatopsychic process].
AB  - Autonomic (heart rates, electroplethysmograms, pneumograms, blood coagulation)
      responses to the threshold and subthreshold concentrations of cordiamine and
      tifene odogenes were studied in 58 healthy young females. There were autonomic
      shifts to subthreshold odogenes and a relationship between the detection
      threshold of a stimulus to the baseline activity of the autonomic nervous system
      and to the amplitude of autonomic changes. It is suggested that autonomic
      (somatic) changes make their contribution to the conscious (psychic) perception
      of a stimulus.

PMID- 8527986
TI  - [Autonomic nervous system and resistance of cardiovascular functions in
      experimental acute emotional stress].
AB  - A relationship between the (metabolic) activity of the sympathetic ganglia, such
      as stellate and upper cervical ones, which innervate the heart and the changes in
      blood pressure was found in rabbits with varying resistance of cardiovascular
      functions to acute experimental emotional stress induced by electric irritation
      of the ventromedial nuclei of the hypothalamus and skin. The activity of the
      upper cervical and stellate ganglia was demonstrate to determine the resistance
      of cardiovascular functions in emotional stress. That of the sympathetic nervous
      system was primarily due to the changes in the function of central regulatory
      links, including the catecholaminergic system of the hypothalamus and the blue
      spot. In addition, there is a decisive role of the sensitivity of baroreceptor
      reflex in the formation of resistance of cardiovascular reactions.

PMID- 8527987
TI  - [Interhemisphere bioelectric asymmetry in the process of recovery in dysfunctions
      of the brain after unilateral lesion].
AB  - The interhemispheric organization of brain electrical processes was shown to
      depend on the lateralization of an injury. The EEG asymmetry was significant with
      a tumor being in the right hemisphere as compared with that of healthy subjects.
      When a tumor was in the left hemisphere, the asymmetry was more considerable than
      that in healthy persons. An analysis of electrophysiological findings and
      clinical symptomatology makes the author to regard interhemispheric asymmetry as
      a significant index of the functional interactions of the hemispheres and the
      nature of a postoperative process.

PMID- 8527988
TI  - [Impulse activity of cortical neurons in systemic organization of behavior
      quanta].
AB  - By using the time course of changes in the level of cortical neuronal freedom,
      the author determined the reflection of intracerebral processes of systemic
      behavioral quanta in the neural impulse activity during cyclic instrumental
      behavior of cats. A direct relationship was found between the duration of
      behavioral stages determining the final operant activity of the animals and the
      number and duration of cerebral integrative performance quanta, the number of
      decision-making stages, the durations of afferent and efferent synthesis stages.
      The study indicated that afferent synthesis predominated over efferent one.

PMID- 8527989
TI  - [Systemic quanta of human productive activity].
AB  - The autonomic maintenance of the productive activity of workers of different
      skills was studied at the electron-optical assembly shop. The concept of systemic
      quantum behavior developed by K. V. Sudakov by which any behavior is regarded as
      a sequence of the discrete systemic units "quanta". It is suggested that the
      discretion of a working behavior reflects that of bioarrhythmic organization of
      physiological functions.

PMID- 8527990
TI  - [Physiological evaluation of the resultant activity of school children working
      with computers].
AB  - The schoolchildren who had achieved high results in computer learning tasks
      showed a regular nature of changes in autonomic parameters, which was in
      concordance with steps taken in goal-oriented activity. Those with low results
      displayed higher and disconcorded changes in autonomic parameters, which were
      interpreted as a predisposition to emotional stress when learning computer tasks.
      The high-result schoolchildren made fewer errors in reaction-time tasks and
      signal differential tasks and spent less time in decision-making. They also
      differed from low-result schoolchildren by showing a higher frequency of beta
      rhythm ECCG from forehead derivations and prevalent alpha-rhythm and also a
      higher proportion of teta-rhythm in the spectra of the forehead, central and
      parietal derivations as well as a higher coherence of alpha-rhythm from the
      forehead and parietal derivations of the left hemisphere.

PMID- 8527991
TI  - [Morphological characteristics of reparative process in tuberculous
      inflammation].
AB  - The morphological analysis of the reparative process in the involvement foci and
      adjacent pulmonary tissue in patients with pulmonary tuberculosis and
      experimental animals during intensive focal resolution has revealed a change in
      the cellular composition: epithelioid cells are replaced by macrophages, T
      lymphocytes SD8 (suppressors) by those CD4 (helpers); actively synthesizing
      fibroblasts and vascular endothelium appear in the area of specific inflammation
      instead of the cells that have a decreased collagen-forming function. The
      employment of various methods for stimulation of cellular reactions (lasers,
      electromagnetic irradiation of the mm range - MM waves, the complex of cytokines)
      leukinferon enables one to alter the qualitative and quantitative cellular
      composition of granulomas, the rate of metabolic processes and the
      differentiation of cells, as well as to examine the regularities of reparative
      reactions more effectively and more purposefully. The perfocally adjacent
      pulmonary tissue wherein the diseased parenchyma and stroma recover has been
      ascertained to be also involved into the reparative process.

PMID- 8527992
TI  - [Neuromediator integration of emotional excitation and mechanisms of stress
      resistance].
AB  - The paper presents a study of the central neurochemical organization of negative
      emotional states changing into emotional stress. The neurotransmitter integration
      of negative emotional excitation wherein, in addition to classical
      neurotransmitters, endogenous peptides, such as substance P, prolactin, which are
      able to enhance emotional stress resistance serves as the basis of formation of a
      negative emotional state An idea of the central peptidergic mechanisms of
      limiting the development of emotional stress is formulated and experimentally
      evidenced within the current concept of the systemic organization of emotions.

PMID- 8527993
TI  - Biotyping of Escherichia coli in microwell plates.
AB  - A simple, inexpensive scheme of eight tests for biotyping strains of Escherichia
      coli in microwell plates is described. The tests comprise primary tests for the
      fermentation of raffinose, sorbose, ornithine, dulcitol and 2-deoxy-D-ribose, and
      secondary tests for rhamnose fermentation, lysine decarboxylation and motility.
      Among a collection of 75 clinical isolates of Esch. coli from 12 patients, 18
      full biotypes designated according to their positive and negative reactions in
      the eight tests were distinguished. These biotypes gave an indication of the
      natural history of patients' infections. Because it provides excellent and
      reliable type discrimination, biotyping can be used in a combination with other
      typing techniques to resolve local epidemiological problems involving Esch. coli.

PMID- 8527994
TI  - Ultrasound-enhanced latex agglutination for the detection of bacterial antigens
      in urine.
AB  - An ultrasound-enhanced latex agglutination technique has been applied to the
      detection of bacteria in urine. The approach combines the use of ultrasound, the
      dilution of latex to allow agglutination with low levels of antigen, and
      microscopy. Using commercially available latex coated with antibody to Esch. coli
      O157 or K1, ultrasound enhanced the detection of Esch. coli strains carrying
      these antigens by x512 and x2048 respectively, compared with the standard test
      card procedure. The latex particles in the commercial kits were 0.4-1.0 micron in
      diameter. As larger particles are more effectively manipulated in a sound field,
      particles of 2.8 microns diameter were coated with antiserum against a urinary
      tract isolate of Esch. coli (SP3112). The application of ultrasound with these
      particles facilitated the detection of 6 x 10(3) cells/mL of Esch. coli SP3112
      within 2 min, a > 10,000-fold increase in sensitivity compared with the normal
      agglutination procedure. The possible exploitation of this technique in the
      clinical laboratory for the rapid, sensitive detection of bacterial antigens in
      urine is discussed.

PMID- 8527995
TI  - Basal cell carcinoma: rapid techniques using cytokeratin markers to assist
      treatment by micrographic (Mohs') surgery.
AB  - In micrographic (Mohs') surgery, routine haematoxylin and eosin stains may
      present difficulties in interpretation of infiltrative (morphoeic) basal cell
      carcinoma. To supplement these routine stains rapid immunoperoxidase and
      immunofluorescence techniques are described using cytokeratin markers Dako LP34,
      MNF 116 or Novocastra NCL-Pan CK on frozen sections to help in the histological
      evaluation of these tumours.

PMID- 8527996
TI  - Comparison of P-glycoprotein expression with in vitro drug sensitivity in fresh
      blast cells from acute myeloid leukaemia patients.
AB  - Anthracyclines and etoposide have been implicated in the multi-drug resistance
      phenotype. The mdr 1 gene encodes for the transmembrane protein P-glycoprotein. P
      glycoprotein expression was measured in the fresh blast cells from 19 patients
      with acute myeloid leukemia using three monoclonal antibodies, C219, JSB-1 and
      MRK 16, and immunocytochemistry with the enzyme alkaline phosphatase as marker.
      Drug resistance can be identified in vitro using the predictive chemosensitivity
      test, the MTT (3-4,5-dimethylthiazol-2,5-diphenyl tetrazolium bromide) assay. In
      order to assess cell viability after drug exposure, this technique utilises the
      ability of cellular dehydrogenase enzymes to reduce the tetrazolium salt MTT to
      formazan. In vitro resistance to multi-drug resistance related cytotoxic agents
      was identified in the blast cells from these patients. This study showed no
      correlation between the results of the MTT assay and P-glycoprotein expression in
      this disease, suggesting either that more sensitive techniques are required to
      measure P-glycoprotein expression or that other drug resistance mechanisms may be
      involved.

PMID- 8527997
TI  - Formaldehyde disinfection in laboratories: limitations and hazards.
AB  - Formaldehyde is a substance hazardous to health, specified in Schedule 1 to the
      British Control of Substances Hazardous to Health Regulations 1988 but still used
      in laboratories as a preservative and for disinfection of surfaces and spaces. In
      this paper we review the properties and hazards of formaldehyde and its common
      laboratory uses, and suggest some precautions and ways of minimising risk from
      those fumigation procedures that carry the greatest risk of exposure to high
      levels of the gas.

PMID- 8527998
TI  - The poisoned patient: the role of the laboratory.
AB  - The past 20 years have seen many advances in methods for the assay of drugs and
      other poisons in biological fluids, with consequent improvement in the
      reliability of results. Therapeutic drug monitoring, drugs of abuse and
      laxative/diuretic screening, and occupational health monitoring have developed
      considerably. The value of assays with overt medico-legal implications and which
      require a high degree of analytical expertise (such as brain death and child
      abuse screening, and cases of suspected iatrogenic poisoning) has become more
      clearly defined. Emergency toxicological analyses are now sometimes requested to
      monitor treatment with (e.g.) chelating agents. However, paracetamol apart, the
      growth in requests for other emergency toxicology analyses has been small, at
      least in the UK. What are the challenges for the future? With the increasing role
      of analytical toxicology, training and quality assurance should have a higher
      profile. Standardisation of the units used in reporting results should also be
      pursued. The need for simple, reliable, low-cost methods for the assay of drugs,
      pesticides and industrial chemicals in biological specimens remains, especially
      in developing countries. Interpretation of results remains difficult and can only
      be improved by construction of an improved data base. Biological monitoring to
      assess occupational/environmental exposure to metals, industrial chemicals and
      pesticides is likely to increase in importance. Interpretation of results in
      individual cases can here be simplified by regulation.

PMID- 8527999
TI  - Human tissue retrieval at post-mortem for musculoskeletal research.
AB  - Laboratory experimentation must attempt to reduce animal involvement, and human
      cadaveric tissue can be a suitable alternative; however, this tissue is a
      potential biohazard, with the transmission of human immunodeficiency and
      hepatitis viruses presenting a very serious problem. In this paper we discuss how
      human tissue can be obtained at hospital post-mortem, and how it can then be
      stored and handled in a laboratory environment, focusing particularly on safety
      issues. We discuss the way in which the Department of Orthopaedic Surgery at
      Leicester University obtained human tissue for research into hip replacement. It
      is hoped that the article will serve as a 'blue-print' for other related research
      projects, where human tissue is required for experimentation.

PMID- 8528000
TI  - Lectin from Codium fragile ssp. tomentosoides conjugated to colloidal gold: a new
      histochemical reagent.
AB  - A new histochemical reagent has been developed utilising a lectin from a marine
      alga for the first time. Colloidal gold was coupled to the N-acetyl-alpha-D
      galactosamine specific lectin from the green alga Codium fragile ssp.
      tomentosoides. The lectin--gold conjugate bound to the membranes of blood-group
      A1 human erythrocytes which were used as a model system. The bound complex could
      be detected, readily, by transmission electron microscopy. This novel reagent
      incorporating a lectin of low molecular weight (15 kDa) has potential value for
      studies of cell-surface topography of a variety of tissues.

PMID- 8528001
TI  - Semi-automated protein assay using microtitre plates: some practical
      considerations.

PMID- 8528002
TI  - Laboratory diagnosis and autofluorescence of Cyclospora.

PMID- 8528003
TI  - Decreased mitochondrial biogenesis in temperature-sensitive cell division cycle
      mutants of Saccharomyces cerevisiae.
AB  - The temperature-sensitive cell division cycle (cdc) G1 mutants cdc28 and cdc35
      show decreased mitochondrial volumes with respect to the wild type strain A364A
      (WT) at the restrictive temperature. Of the three criteria of mitochondrial
      biogenesis studied, that is, number of mitochondria per cell, relative area of
      the cell occupied by mitochondria, or relative area of mitochondria occupied by
      inner membranes, only the second indicator was significantly lower in cdc mutants
      than in the WT. The mitochondrial inner membranes development did not compensate
      for the decrease in the organelles volume. Apparently, the reduced mitochondrial
      biogenesis was not due to the temperature shift because the relative area of the
      cell occupied by mitochondria was already significantly lower at 25 degrees C in
      cdc mutants. The specific fluxes of oxygen consumption confirmed that the
      respiratory capacity of cdc mutants is largely impaired in respect to the WT.
      Cdc28 and cdc35 mutants of Saccharomyces cerevisiae had been previously shown to
      exhibit high respiratory quotients (from 3 to 7) in respect to the WT (RQ
      approximately 1.0), which correlated with carbon and energy uncoupling probably
      the result of glucose-induced catabolite repression [Aon MA, Monaco ME, Cortassa
      S (1995) Exp Cell Res 217, 42-51; Monaco ME, Valdecantos PA, Aon MA (1995) Exp
      Cell Res 217, 52-56].

PMID- 8528004
TI  - Legionella pneumophila has two 60-kilodalton heat-shock proteins.
AB  - Legionella pneumophila is a thermotolerant bacterium. To learn more about the
      thermal adaptation of this organism, we studied the properties of the Legionella
      60-kDa heat-shock protein (MopA, GroEL-analog, HtpB, Lp-Hsp60) in L. pneumophila
      and in an Escherichia coli strain containing the cloned gene. Lp-Hsp60 was found
      in both cytosol and membrane fractions; however, Lp-Hsp60 in the membrane
      fraction of L. pneumophila was slightly larger than Lp-Hsp60 in the cytosol. In
      contrast, both membrane-associated and cytosolic Lp-Hsp60 in the E. coli clone
      were similar in size to the smaller cytosolic Lp-Hsp60 of L. pneumophila. While
      peptide mapping suggests there are differences between the two proteins, the
      larger membrane-associated Lp-Hsp60 and the smaller cytosolic LP-Hsp60 shared
      Legionella-specific and E. coli GroEL cross-reacting epitopes, and the sequence
      of their first 20 N-terminal amino acids was identical. Further, Southern blot
      analysis of EcoRI-digested chromosomal DNA from several strains of L. pneumophila
      showed two fragments reacting with an htpAB-operon probe. In summary, L.
      pneumophila contains two Hsp60 proteins, and possibly two hsp60 genes.

PMID- 8528005
TI  - Isolation and characterization of a temperate bacteriophage from a ruminal
      acetogen.
AB  - Nine acetogenic bacterial cultures recently isolated from the bovine rumen were
      tested for phage susceptibility by plaque formation. Both clear plaques and
      plaques with turbid centers were occasionally seen, but could not be used
      repeatedly to lyse pure cultures of acetogens, suggesting the possibility of a
      temperate phage. Five of the nine acetogenic isolates showed a response to
      mitomycin C induction. Acetogenic isolate H3HH was chosen for further study
      because it produced the greatest lysogenic response to mitomycin C. The
      bacteriophage was induced with mitomycin C, examined by transmission electron
      microscopy, and shown to have a hexagonal head (diameter, 59 eta m), a long
      flexible tail (192 eta m), and a flat collar (diameter, 31 eta m). The
      bacteriophage was classified within Bradley's group B. Bacteriophage DNA was
      determined to contain 36.2 kilobases of linear double-stranded DNA.

PMID- 8528006
TI  - Molecular cloning and nucleotide sequence of the 90k serine protease gene, hspK,
      from Bacillus subtilis (natto) No. 16.
AB  - We previously reported purification and characterization of a 90k serine protease
      with pI 3.9 from Bacillus subtilis (natto) No. 16 [Kato et al. 1992 Biosci
      Biotechnol Biochem 56:1166]. The enzyme showed different and unique substrate
      specificity towards the oxidized B-chain of insulin from those of well-known
      bacterial serine proteases from Bacillus subtilisins. The structural gene, hspK,
      for the 90k serine protease was cloned and sequenced. The cloned DNA fragment
      contained a single open reading frame of 4302 bp coding a protein of 1433 amino
      acid residues. The deduced amino acid sequence of the 90k-protease indicated the
      presence of a typical signal sequence of the first 30 amino acids region and that
      there was a pro-sequence of 164 amino acid residues after the signal sequence.
      The mature region of the 90k-protease started from position 195 of amino acid
      residue, and the following peptide consisted of 1239 amino acid residues with a
      molecular weight of 133k. It might be a precursor protein of the 90k-protease,
      and the C-terminal region of 43k might be degraded to a mature protein from the
      precursor protein. The catalytic triad was thought to consist of Asp33, His81,
      and Ser259 from comparison of the amino acid sequence of the 90k-protease with
      those of the other bacterial serine proteases. The high-molecular-weight serine
      protease, the 90k-protease, may be an ancient form of bacterial serine proteases.

PMID- 8528007
TI  - Photoreactivation in the genus Bacillus.
AB  - Photoreactivation of ultraviolet radiation-induced DNA damage was examined in
      exponential-phase cells of six mesophilic species of the genus Bacillus. Under
      the experimental conditions used, it was observed that the laboratory strains B.
      cereus strain T and B. thuringiensis var. thuringiensis strain NRRL-B4039
      exhibited strong photoreactivation (86-fold and 70-fold respectively). Bacillus
      licheniformis strain ATCC 8480 exhibited moderate (15-fold) photoreactivation.
      Weak photoreactivation was observed in B. subtilis strain 168 (4-fold) and B.
      megaterium strain QM B1551 (3.4-fold). Bacillus amyloliquefaciens strain H
      demonstrated no detectable photoreactivation.

PMID- 8528008
TI  - Influence of salt concentration on the susceptibility of moderately halophilic
      bacteria to antimicrobials and its potential use for genetic transfer studies.
AB  - The influence of salinity on the susceptibility of 13 moderately halophilic
      collection strains belonging to the genera Chromohalobacter, Deleya, Halomonas,
      Vibrio, and Volcaniella to 10 common antimicrobials has been studied. Three
      different patterns of tolerance were found when salinity was varied from 10 to 1%
      (wt/vol) total salts in the testing media. The first one included the responses
      to ampicillin and rifampicin, where only minimal effects on the susceptibility
      were found. All moderate halophiles showed a high sensitivity to rifampicin
      regardless of the salt concentration. In the second group, including the
      responses to the aminoglycosides gentamycin, kanamycin, neomycin, and
      streptomycin, a remarkable and gradual increase of the toxicity was detected at
      lower salinities. Thirdly, the highest heterogeneity was found for the rest of
      antimicrobials assayed (trimethoprim, nalidixic acid, spectinomycin, and
      tetracycline), where the effect of salinity was moderate and dependent on both
      the individual strain and the antimicrobial tested. The data presented here
      should facilitate genetic studies on moderate halophiles. Thus, they simplify the
      design of selection media for genetic exchange experiments. Besides, by using low
      salinity media, genes encoding resistance to a number of antimicrobials,
      especially to aminoglycosides, can be used as genetic markers for plasmids or
      transposons to be transferred to these extremophiles.

PMID- 8528010
TI  - Specific PCR detection and identification of Xylella fastidiosa strains causing
      citrus variegated chlorosis.
AB  - By cloning and sequencing specific randomly amplified polymorphic DNA (RAPD)
      products, we have developed pairs of PCR primers that can be used to detect
      Xylella fastidiosa in general, and X. fastidiosa that cause citrus variegated
      chlorosis (CVC) specifically. We also identified a CVC-specific region of the X.
      fastidiosa genome that contains a 28-nucleotide insertion, and single base
      changes that distinguish CVC and grape X. fastidiosa strains. When using RAPD
      products to develop specific PCR primers, we found it most efficient to screen
      for size differences among RAPD products rather than presence/absence of a
      specific RAPD band.

PMID- 8528009
TI  - Influence of the culture medium on the expression of surface polypeptides of
      Yersinia enterocolitica.
AB  - Three polypeptides (200, 46, and 25 kDal) encoded by the virulence plasmid were
      detected by SDS-PAGE in the outer membrane of Yersinia enterocolitica 09 grown at
      37 degrees C in brain-heart infusion medium. Bacteria grown at the same
      temperature in the tissue culture medium RPMI 1640 expressed five additional
      polypeptides (170, 135, 118, 100, and 98 kDal), but the 25-kDal band was not
      seen. The protein profile in RPMI 1640 resembles the expression pattern displayed
      by yersiniae when grown in vivo. The immunoblot of total membrane proteins of
      bacteria grown in brain-heart infusion medium revealed eight plasmid-encoded
      polypeptides, four of which were also in the outer membrane preparations,
      including a 28-kDal polypeptide. These peptides do not coincide with known
      plasmid-encoded outer membrane proteins.

PMID- 8528011
TI  - Molecular mechanism of follicle rupture during ovulation.

PMID- 8528012
TI  - Cell migration from the olfactory placode and the ontogeny of the neuroendocrine
      compartments.
AB  - The olfactory placode and its derivative, the olfactory pit, give rise to several
      different populations of migrating cells, which contribute to drive the
      organization of the prosencephalon, but also to form a part of the central
      neuroendocrine compartments. Some cell types are seemingly transient and can play
      a role in the establishment of the final connections. The understanding of the
      mechanisms involved in the migration and differentiation of these cell
      populations can give an insight on the interplay between peripheral structures
      and central nervous system and on the mechanisms of commitment, phenotype
      selection and control for neuroendocrine cells able to selectively "colonize" the
      brain.

PMID- 8528013
TI  - In vitro reactions of coelomocytes against sheep red blood cells in the solitary
      ascidian Halocynthia roretzi.
AB  - Coelomocytes (blood cells) of the solitary ascidian Halocynthia roretzi were
      placed in culture to which sheep red blood cells (SRBCs) were introduced. Their
      reactions against SRBCs were observed by phase-contrast, time-lapse video and
      scanning electron microscopy. Three cell types, the phago-amoebocyte, the
      vacuolated cell and the fusogenic phagocyte, reacted to the SRBCs by
      phagocytosis. The vacuolated cell occasionally discharged the material of their
      vacuoles at the time of or shortly after ingesting the SRBC. The lymphoid cell
      captured SRBCs, but did not ingest them. Three other cell types, the fibroblastic
      cell, the giant cell and the multipolar cell, showed no reaction to the SRBC. The
      SRBCs captured by the lymphoid cells were transferred either to phago-amoebocytes
      or fusogenic phagocytes, probably to be ingested. Such collaboration between
      multifunctional cell is considered to characterize the cellular defense mechanism
      of H. roretzi.

PMID- 8528014
TI  - Puromycin induces apoptosis of developing chick sympathetic neurons in a similar
      manner to NGF-deprivation.
AB  - Survival of sympathetic neurons of chick embryo depends on nerve growth factor
      (NGF), and removal of NGF from culture medium caused apoptosis. We found that
      puromycin, an analogue of aminoacyl-tRNA, also induced apoptosis in a manner
      quite similar to that caused by NGF-deprivation. First, transcriptional
      inhibitors such as actinomycin D and alpha-amanitin effectively prevented both
      apoptoses, suggesting a requirement of gene expression. Second, the apoptoses
      were effectively prevented by translational inhibitors acting on peptidyltransfer
      reaction, such as anisomycin and blasticidin S. On the other hand, emetine, an
      inhibitor of translocation of peptidyl-tRNA, was not effective. Finally, NGF
      deprivation and puromycin-addition affected the same three phosphorylated
      proteins to undergo dephosphorylation or to be eliminated. Besides, these changes
      were suppressed by anisomycin and blasticidin, but not by emetine. Based on these
      findings, we discuss the mechanism to induce apoptosis of chick sympathetic
      neurons.

PMID- 8528015
TI  - Spontaneous cytotoxic earthworm leukocytes kill K562 tumor cells.
AB  - Earthworm coelomocytes may act as effector cells which destroy targets in vitro.
      In a 51Cr release assay, Lumbricus coelomocyte effectors showed lytic activities
      of 3-14% against K562 human tumor cells when incubated 1-4 hr at 23 degrees C or
      37 degrees C. Cytotoxicity was correlated with effector: target ratio. However,
      targets were not killed by incubating them in cell-free, 0.2 micron filtered
      coelomic fluid. The supernatant from coelomocytes cultured alone failed to kill
      K562 targets but coelomocyte lysates were toxic to target cells in a
      concentration-dependent manner. Coelomocytes were examined using transmission
      electron microscopy (TEM) and scanning electron microscopy (SEM). When effectors
      and targets were examined under TEM, we found close apposition of effector
      granulocytic coelomocytes and target cell membranes but not with coelomocytes nor
      eleocytes at up to 15 min incubation. By SEM, effector cells appeared not only to
      be in close contact with targets, but instances of target lysis were observed.
      These results suggest that effector cell/target cell contact is essential for
      cytotoxicity to occur.

PMID- 8528016
TI  - The cDNA-derived amino acid sequence of chain II of the heterodimeric hemoglobin
      from the blood clam Barbatia virescens.
AB  - The blood clam Barbatia virescens expresses a unique heterodimeric hemoglobin
      consisting of chains I and II in erythrocytes. This is in sharp contrast to the
      tetrameric (alpha 2 beta 2) and polymeric two-domain hemoglobins of the
      congeneric species Barbatia reeveana and Barbatia lima. The 3' and 5' parts of
      the cDNA of B. virescens chain II have been amplified separately by polymerase
      chain reaction (PCR), and the complete nucleotide sequence of 690 bp was
      determined. The open reading frame is 477 nucleotides in length and encodes a
      protein with 158 amino acid residues, of which 120 amino acids were identified
      directly by the protein sequencing of the peptides obtained from digestions with
      trypsin, S. aureus V8 protease and pepsin. The mature protein begins with the
      blocked Ser, and thus the N-terminal Met is cleaved away. The molecular mass for
      the protein was calculated to be 17605 Da. The cDNA-derived amino acid sequence
      of B. virescens heterodimeric chain II shows the highest homology (42%) with that
      of B. virescens chain I, but shows lower homology (32-35%) with those of
      tetrameric alpha and beta chains of B. lima. This indicates that B. virescens
      chains I and II do not correspond to B. lima alpha and beta chains, namely the
      heterodimeric hemoglobin is a unique gene product expressed only in B. virescens.

PMID- 8528017
TI  - The effects of testosterone and estradiol on mast cell number in the harderian
      gland of the frog, Rana esculenta.
AB  - The Harderian gland (HG) of the frog Rana esculenta contains mast cells in the
      interstitial tissue. The mast cell number (MCN) is influenced by sex hormones.
      Gonadectomy in both sexes provoked a decrease in MCN in January, while no effect
      was observed in September. Sex hormone-replacement therapy gave different
      results; estradiol treatment in castrated males and females always increased MCN,
      while testosterone did not. Acute estradiol treatment provoked an increase in MCN
      on days 2 and 4 of treatment and the morphology of the glandular compartment
      appeared normal. On days 8, 10 and 12 of treatment the MCN drastically decreased.
      The majority of glandular acini appeared strongly disorganized and the
      interstitial tissue became hypertrophic in concomitance with an increased
      vascularization. Our results suggest that estradiol acts by stimulating mast
      cells and acute estradiol treatment provokes proliferation of interstitial
      connective tissue together with glandular cells damage.

PMID- 8528018
TI  - Orientation of the toad, Bufo japonicus, toward the breeding pond.
AB  - A variety of orientation cues has been suggested for the migration to the
      breeding site in adult amphibians. We categorized the cues into the following 3
      groups: 1) cues from the breeding pond such as male calling and pond odors, 2)
      celestial cues such as the sun light and the magnetic field of the earth and 3)
      cues from the area or route of the migration which compose a local map such as a
      visual and olfactory maps. To determine which of these is used by the toad, Bufo
      japonicus, we designed and conducted a displacement experiment in which migrating
      toads from one direction were transported to the ground in the opposite side of
      the pond. The displaced toads were completely disoriented and moved to random
      directions. We conclude that the toad uses a local map to orient to the breeding
      pond and cues from celestial bodies and the pond are not used. We also found that
      adult toads tracked the same route on both trips from and to the pond. This
      suggests that the local map was memorized by newly metamorphosed toads at their
      first terrestrial trip from the pond. The next step of our study was to determine
      what sense is used to receive the cue. We found blind toads, whose upper and
      lower eye-lids were stitched together, could reach the pond at a similar rate
      with the sham-operated and intact toads. However, anosmic toads, whose olfactory
      mucosa were damaged by the treatment with a 5% silver nitrate solution, rarely
      reached the pond.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528019
TI  - Neurotrophin-3 augments steroid secretion by hamster ovarian follicles in vitro.
AB  - Innervation of the ovary is known to be affected by neurotrophic factors; mRNA
      for some of these molecules and their low-affinity receptors have been identified
      in ovarian follicular tissue. We attempted to determine whether neurotrophin (NT
      3) exerts a non-neuronal impact on the ovary, affecting follicular estradiol
      secretion via a possible humoral action. Ovaries were excised from mature Golden
      Syrian Hamsters (Mesocricetus auratus) and large preovulatory follicles were
      removed by microdissection. Follicles were incubated for 72 hr in control medium,
      or medium containing 10 ng, 100 ng, or 1000 ng/ml NT-3. After culture, medium
      samples were assayed for estradiol content. NT-3 exerted dichotomous effects,
      depending on concentration: NT-3 augmented mean estradiol output two-fold at 100
      ng/ml, while 1000 ng/ml NT-3 decreased estradiol secretion back to control
      levels. By 48-72 hr in culture, all groups exhibited a significant decline in
      mean estradiol secretion due presumably to diminished viability, independent of
      neurotrophin action. These data suggest a humoral role for NT-3 in estradiol
      secretion of preovulatory follicles in culture.

PMID- 8528020
TI  - Regular pulse emission in some megachiropteran bats.
AB  - We recorded vocalizations of megachiropteran bats, Cynopterus brachyotis, C.
      horsfieldi, Megaerops ecaudatus and Macroglossus sobrinus as they were held in
      our hands, in a hanging position or moved up and down, simulating flight. All
      four species produced regular audible tone pulses with a frequency spectrum of
      less than 9 kHz (peak at 4-6 kHz). The duration of a single pulse varied from
      14.9 to 23.6 msec on average among these species. The interpulse interval was
      between 108.3 and 127.7 msec. In M. ecaudatus and M. sobrinus, double pulses were
      occasionally emitted, with interpulse intervals averaging 39 msec and 31 msec,
      respectively. The regular pulse emission may indicate that the bats studied use
      sounds to probe space.

PMID- 8528021
TI  - The World Health Organization's Expert Committee on drug dependence: comments on
      the 28th report (1994)

PMID- 8528022
TI  - Population science, prejudice and policy on alcohol.

PMID- 8528023
TI  - Do role-model societies exist?

PMID- 8528024
TI  - Alcohol policy and the dilemma of Africa.

PMID- 8528025
TI  - Zambia: the need for a national 'Policy Options Working Group'.

PMID- 8528026
TI  - Alcohol policy and the public good: a Chinese view.

PMID- 8528027
TI  - A critique of chapter 3: "Individual drinking and degree of risk".

PMID- 8528028
TI  - A major contribution to improve the science policy discussion.

PMID- 8528029
TI  - The value of independence.

PMID- 8528030
TI  - The economic costs of alcohol-related absenteeism and reduced productivity among
      the working population of New Zealand.
AB  - Lost productivity accounts for a significant proportion of the total cost of
      alcohol. This study quantifies the costs associated with alcohol consumption
      using survey data collected from four alcohol surveys conducted in Auckland
      between November 1990 to May 1992. The total sample size was 4662, of which 2638
      were drinkers in paid employment. A computer-assisted telephone interviewing
      system was used to interview a random sample that closely matched the Auckland
      population. Respondents gave information about their typical alcohol consumption
      and frequency of absences from paid employment which were a result of their
      drinking. They also gave a report of the number of times in the past 12 months
      when they felt their work had been impaired as a result of their drinking. The
      cost of absenteeism was recorded as the number of times a respondent reported
      time away from work multiplied by gross income. Estimates of reduced work
      efficiency were derived from US figures, which estimated a 25% reduction in work
      performance among heavy alcohol users; 3.7% of the sample reported alcohol
      related absences and 12% reported reduced efficiency days. There was a
      significant difference in both the number and cost of absentee and reduced
      efficiency days reported between the top 10% and the bottom 10% drinkers. A
      conservative estimate of alcohol-related lost productivity among the working
      population of New Zealand (with a population of 3.4 million and a per capita
      absolute alcohol consumption of 9.7 litres) was found to be $57 million per year.

PMID- 8528031
TI  - Alcohol and suicide: a comparative analysis of France and Sweden.
AB  - The aim of this paper is to test the hypothesis that the effect of alcohol
      consumption on suicide risk is stronger in Sweden than in France. The rationale
      of the hypothesis is that we should expect a difference between the two countries
      with respect to: (i) the composition of alcohol abusers; and (ii) the degree to
      which heavy drinking is accepted. Analyses of time-series data provide support
      for the hypothesis: the effect of per capita consumption of alcohol is
      significantly stronger in Sweden than in France.

PMID- 8528032
TI  - Prague women's drinking before and after the 'velvet revolution' of 1989: a
      longitudinal study.
AB  - Results are presented of a follow-up study in which a representative sample of
      608 Prague women aged 20-49 years in 1987 at first interview was re-interviewed
      in 1992 3 years after the resolution that ended the 41 years of the Communist era
      in Czechoslovakia. The average yearly consumption of alcohol in the followed-up
      female sample increased between 1987-92 from a reported 3.6 litres to 4.8 litres.
      The percentage of heavier drinkers (with average daily consumption of over 20 g
      alcohol) increased from 7.2% to 14.0%. The women expressed increased tolerance of
      drunkenness in their attitudes to drinking. The consumption increase was mainly
      due to increased drinking frequency of spirits and to increased quantity of beer
      consumed per occasion. The consumption increase was largest in women working as
      free-lance and the newly emerging self-employed women; economically inactive
      women did not increase their consumption. Women who reported a positive impact of
      the socio-political changes on their personal lives and an expansion of social
      contacts also reported larger than average consumption increases. A coincidence
      of stressful, possibly self-inflicted, life events and increased alcohol use was
      observed and interpreted as probably a two-way influence.

PMID- 8528033
TI  - Predictive capacity of the AUDIT questionnaire for alcohol-related harm.
AB  - The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item questionnaire
      designed to screen for hazardous and harmful alcohol consumption. We examined its
      ability to predict alcohol-related illness and social problems, hospital
      admission and mortality over a 2-3-year period. At initial interview, 330
      ambulatory care patients were assessed using a detailed interview including the
      AUDIT questions and laboratory tests. After 2-3 years, 250 (76%) subjects were
      reassessed and their experience of alcohol-related harm determined. Of those who
      scored eight or more on AUDIT at initial interview, 61% experienced alcohol
      related social problems compared with 10% of those with lower scores (p <
      0.0001); they also had a significantly greater experience of alcohol-related
      medical disorders and hospitalization. AUDIT score was a better predictor of
      social problems and of hypertension than laboratory markers. Its ability to
      predict other alcohol-related illnesses was similar to the laboratory tests.
      However, gamma glutamyltransferase was the only significant predictor of
      mortality. We conclude that AUDIT should prove a valuable tool in screening for
      hazardous and harmful alcohol consumption so that intervention can be provided to
      those at particular risk of adverse consequences.

PMID- 8528034
TI  - Heavy drinking in the restaurant business: the role of social modelling and
      structural factors of the work-place.
AB  - The role of social modelling and structural factors of the work-place in
      predicting the probability of heavy drinking was investigated in a sample of 3267
      Norwegian male and female waiters and cooks. In the logistic regression analysis,
      the probability of heavy drinking was increased by two social modelling factors
      and one structural factor. Having co-workers who, at least weekly, took an end-of
      work drink at the work-place gave an odds ratio for heavy drinking of 2.8 (95% CI
      1.9-4.1), and having co-workers who went out after work at least every week gave
      an odds ratio of 1.8 (95% CI 1.2-2.8). Working at a place with a liberal alcohol
      policy gave an odds ratio 1.5 (95% CI 1.1-2.2). Among the background factors,
      only household type significantly predicted heavy drinking. As compared with
      living with children, the odds for heavy drinking when living alone was 4.3 (95%
      CI 2.9-6.4). The results indicate that preventive measures in the restaurant
      business should not only concentrate on the individual, but also deal with
      factors related to the occupational activity that promote and sustain heavy
      drinking.

PMID- 8528035
TI  - Assessing consistency of responses to questions on cocaine use.
AB  - This study examines consistency of self-reported responses to items within the
      questionnaire of a multi-site, prospective study of drug abuse treatment in the
      United States (DATOS). The analyses use data from 2842 interviewer-administered
      intake interviews. Questions that were logically related are paired and responses
      compared. The questions cover three topics: (1) age at which different types of
      cocaine was used, (2) reports on most recent use and (3) frequency of cocaine use
      during period of "heaviest" use. Responses are coded as consistent, inconsistent,
      or as survey administration error. The latter is related to interviewer errors
      such as erroneous skip pattern, out-of-range responses, "don't know" responses,
      missing data, or illegible responses. Contrary to expectations inconsistent
      responses were relatively rare in this study, with fewer than 5% (0.5-4.6%) of
      respondents reporting inconsistent answers for pairs of logically related
      questions. A careful review of responses also found few survey administration
      errors (0.2-1.3%).

PMID- 8528036
TI  - Psychoactive substance use in three sites in China: gender differences and
      related factors.
AB  - One year prevalence rates for psychoactive substance use are reported based on a
      community survey in Hunan, Helongjiang and Jiangsu. Data were gathered on more
      than 14,000 respondents (15-65 years old). The drinking rates ranged from 58.3%
      to 82.6% for men and from 16.3% to 31.4% for women. Smoking rates ranged from
      64.9% to 68.1% for men and from 0.1% to 20.5% for women. Most drinkers were light
      users and most smokers were heavy users. Illicit drug use was found in the Hunan
      site. For both frequency and quantity of psychoactive substance use, women are
      lighter consumers than males (except for the use of minor tranquillizers and
      analgesics). Psychosocial factors related to drinking and smoking are also
      investigated in this study.

PMID- 8528037
TI  - Drug use among secondary school students in Zimbabwe.
AB  - A survey of drug use carried out in Zimbabwe in 1990/91 involved 2783 students
      from five different school categories in two provinces. Results show existence of
      use and experimenting, although prevalence is generally lower than corresponding
      European figures. Alcohol and tobacco is more common among urban than rural
      students and more common among private than public school students. Cannabis
      prevalence varies less, although high density urban school students report higher
      figures than others. Prevalence of inhalants is highest at private schools. Use
      of alcohol, tobacco and cannabis increases with age for both sexes, contrary to
      inhalants which shows a decreasing tendency for females and minimal variations
      across age-groups for males. Scale analysis for urban students produced results
      similar to European studies, demonstrating a stage pattern beginning with alcohol
      and tobacco, followed by cannabis or inhalants. The same pattern could not be
      demonstrated among rural students. It is argued that drug use among urban
      students is more developed not only quantitatively but also in that the use of
      different drugs is systematically strongly intercorrelated. Pattern variations
      between school-types may also reflect a stronger external or western influence on
      urban than rural adolescent drug use behaviour.

PMID- 8528038
TI  - The role of autonomic arousal in problem gambling.
AB  - The present study investigated the role of arousal in problem gambling. Three
      groups of subjects were recruited into the study corresponding to problem
      gamblers, high and low frequency social gamblers. For the two gambling groups,
      the preferred form of gambling was poker machine playing. Five different
      conditions were employed in order to determine under which conditions gambling
      related cues were related to increased autonomic arousal, as measured by skin
      conductance level (SCL), heart rate (HR) and frontalis electromyography (EMG).
      The five conditions were a neutral task, a videotaped poker machine gambling
      scenario presented with and without distraction, a personally relevant "win"
      situation and a videotaped horse race. Comparisons between responses for the
      videotaped poker machine gambling stimuli versus a horse-racing video task
      demonstrated differences only for the problem gambling group and only for SCL. No
      differences between these tasks emerged on the HR and EMG indices and no
      differences were evident for either of the social gambling groups. No changes
      were observed in any group when subject's cognitions were prevented by asking
      patients to count the number of wins made during the video play period while
      watching the same poker machine video. However, when personally relevant
      situations were presented and compared to a neutral task, differences were
      observed in all three groups. However, the nature of these differences varied
      between the groups and the different indices of arousal. For problem gamblers,
      increases were evident in all three measures. Increases were also observed for
      the control groups in comparison to the neutral task, but only in HR and SCL and
      not for EMG. For HR, the increases were equivalent across all three gambling
      groups. However, for SCL the problem gambling group became significantly more
      aroused than the control groups, but no differences were observed between the
      high and low frequency gamblers. Only the problem gambling groups evidenced
      significant increases in the personally relevant task compared to the neutral
      task for EMG. Theoretical and clinical implications of these results for the
      development, maintenance and treatment of problematic levels of gambling are
      discussed.

PMID- 8528039
TI  - Nicotine patch therapy for smoking cessation in recovering alcoholics.
AB  - In a post hoc analysis of prior nicotine patch studies, we analysed findings in
      357 subjects (43 recovering alcoholics, 314 non-alcoholics) to determine if
      recovering alcoholic smokers were more nicotine dependent than non-alcoholics and
      whether the efficacy of nicotine patch therapy was comparable. The Self
      Administered Alcoholism Screening Test was used to identify recovering
      alcoholics. Recovering alcoholics had significantly higher mean smoking rates
      (cigarettes per day), Fagerstrom scores and baseline serum nicotine and cotinine
      than non-alcoholics. Among a subset of 240 subjects with a comparable treatment
      protocol, smoking cessation rates at the end of nicotine patch therapy were
      similar in recovering alcoholics (46%) and non-alcoholics (47%) receiving active
      22 mg patches but higher than the respective placebo groups (17% and 19%). The 1
      year rate was significantly (p = 0.005) higher in the non-alcoholic group
      assigned to an active patch (31%) compared to placebo (14%). For recovering
      alcoholics, the rates were lower and not significantly different (active 0%,
      placebo 11%). Recovering alcoholic smokers are likely to be more nicotine
      dependent than non-alcoholic smokers but can achieve comparable short-term
      cessation rates with nicotine patch therapy. Use of an objective, validated
      measure of alcohol dependence is indicated in clinical trials when it is
      desirable to know whether the subjects are active or recovering alcoholics.

PMID- 8528040
TI  - Are males actually heavier drinkers than females?

PMID- 8528041
TI  - Harm reduction, not alcohol consumption reduction.

PMID- 8528042
TI  - Origin of high-grade lymphomas in Richter syndrome.
AB  - Patients with B cell chronic lymphocytic leukemia (CLL) occasionally develop high
      grade B cell lymphomas that are associated with constitutional symptoms, rapidly
      progressive lymphadenopathy, and swift clinical deterioration. Now known as
      Richter syndrome, this symptom complex develops in approximately 5% of all
      patients with CLL. Structural and molecular analysis of the immunoglobulin (Ig)
      genes have allowed investigators to define the clonal relationship between the
      leukemia and lymphoma cells of a given patient. In most cases the aggressive
      lymphoma evolves from the original leukemia cell clone. However, in some cases
      the lymphoma apparently represents a second malignancy. Differentiation between
      these two types of lymphoma may have clinical significance. Further investigation
      is required to allow for identification of CLL patients who are at risk for
      developing Richter syndrome and to understand factors involved in its
      etiopathogenesis.

PMID- 8528043
TI  - Cytokine receptor genes: structure, chromosomal location, and involvement in
      human disease.
AB  - Haemopoietic cytokines regulate haemopoietic cell function via specific cell
      surface receptors. These receptors are members of a large superfamily of
      transmembrane proteins and are characterised by a 200 amino acid extracellular
      sequence encoding the ligand binding domain. Several of the genes for members of
      this superfamily have now been characterised at the molecular level revealing a
      highly conserved organisation and a number of these genes have been localised
      cytogenetically. The recent finding that genes for the IL-3 and GM-CSF receptor
      alpha chain subunits colocalise to a small region of the pseudoautosomal region
      and the observation that the LIF receptor locus is present in a cluster of
      receptor genes on chromosome 5 suggest the possibility that subsets of cytokine
      receptor genes may be organised into clusters. This possibility is discussed and
      the potential significance of cytokine receptor gene clusters is assessed.
      Several of the receptor genes are known to be involved in inherited disorders and
      there is evidence to suggest lesions in cytokine receptor genes could have a role
      in leukaemia. We review the gene organisation, localisation and involvement in
      disease for the known cytokine receptor loci. This large family of receptors is
      expanding with the steady discovery of new members--all of which have the
      potential to be involved in human disorders.

PMID- 8528044
TI  - CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy.
AB  - The CD19 antigen plays an important role in clinical oncology. In normal cells,
      it is the most ubiquitously expressed protein in the B lymphocyte lineage. CD19
      expression is induced at the point of B lineage commitment during the
      differentiation of the hematopoietic stem cell, and its expression continues
      through preB and mature B cell differentiation until it is finally down-regulated
      during terminal differentiation into plasma cells. CD19 expression is maintained
      in B-lineage cells that have undergone neoplastic transformation, and therefore
      CD19 is useful in diagnosis of leukemias and lymphomas using monoclonal
      antibodies (mAbs) and flow cytometry. Interestingly, CD19 is also expressed in a
      subset of acute myelogenous leukemias (AMLs) indicating the close relationship
      between the lymphoid and myeloid lineages. Because B lineage leukemias and
      lymphomas rarely lose CD19 expression, and because it is not expressed in the
      pluripotent stem cell, it has become the target for a variety of
      immunotherapeutic agents, including immunotoxins. Treatment of non-Hodgkin's
      lymphoma (NHL) and acute lymphocytic leukemia (ALL) with anti-CD19 mAbs coupled
      to biological toxins has proven to be effective in vitro and in animal models,
      and has shown some promising results in Phase I clinical trials. Recently, the
      analysis of anti-CD19 effects on lymphoma cell growth has highlighted a novel
      mechanism of immunotherapy. Engagement of cell surface receptors like CD19 by
      mAbs can have anti-tumor effects by the activation of signal transduction
      pathways which control cell cycle progression and programmed cell death
      (apoptosis).

PMID- 8528045
TI  - Alterations of the retinoblastoma a susceptibility gene in chronic lymphocytic
      leukemia.
AB  - Research in recent years has shown that malignant transformation is a genetic
      multistep process. This holds true not only for in-vitro model systems, but has
      also been elegantly shown in-vivo, as in colorectal cancer. Chronic lymphocytic
      leukemia (CLL) is the most frequent leukemia in Western countries and occurs
      mainly in elderly patients, suggesting that in this form of leukemia, cumulative
      molecular lesions may be necessary for transformation. However, the molecular
      background is unknown in most cases. Cytogenetic aberrations may be used as
      markers for genes involved in the process of malignant transformation. In CLL,
      the most frequently observed structural cytogenetic lesion is a
      deletion/translocation involving the long arm of chromosome 13, a region where
      the retinoblastoma susceptibility gene (Rb-gene) has been mapped (13q14). Many
      groups have studied the question as to whether alterations of the Rb-gene play a
      causal role in the pathogenesis of CLL. This review deals with recent data
      indicating that i) the Rb-gene may be altered in a minority of CLL cases, and ii)
      there may be another gene localized on chromosome 13q14 that may be important in
      the molecular biology of CLL.

PMID- 8528046
TI  - The use of GM-CSF and G-CSF in the treatment of acute leukemias.
AB  - The administration of HGF after chemotherapy for patients with acute leukemia
      does not appear to decrease the CR rate or to increase the relapse rate while the
      risk of leukemic clone stimulation in this context is probably low, even in AML.
      Time to neutrophil recovery is generally reduced but in only a few studies does
      this result in a better CR rate. Up to now, the event free survival and the
      overall survival has never been prolonged by the administration of HGF after
      induction chemotherapy only. The attractive approach of priming by HGF has not
      yet proved useful and many questions still remain regarding the optimal
      administration. Accordingly, one cannot recommend routine use of HGF in the
      treatment of acute leukemia. Longer follow up of the ongoing trials and further
      studies are still required in order to appreciate the exact impact of the use of
      GM-CSF or G-CSF for this particular indication.

PMID- 8528047
TI  - Erythropoiesis and erythropoietin in multiple myeloma.
AB  - In this review, the pathophysiology and treatment of the anemia of multiple
      myeloma will be examined. While the anemia of cancer has multiple causes, an
      important component is labeled the "anemia of chronic disease" which is
      characterized by the combination of a shortened erythrocyte survival with failure
      of the bone marrow to increase red cell production in compensation. Depressed
      erythropoiesis is itself related to a combination of factors, including impaired
      availability of storage iron, inadequate erythropoietin response to anemia, and
      overproduction of cytokines which are capable of inhibiting erythropoiesis. These
      cytokines are involved in the retention of iron in the reticuloendothelial
      system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin
      production by the kidney, and may exert direct inhibitory effects on erythroid
      precursors. While overproduction of several such cytokines, including IL-6, IL-1
      and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it
      is still unclear whether they are directly involved in the pathogenesis of the
      anemia which develops. Although several mechanisms, such as hemodilution,
      bleeding, and decreased red cell survival operate, the anemia is mostly caused by
      defective erythropoietic activity. This in turn is partly explained by inadequate
      erythropoietin (Epo) production even in some patients without renal impairment.
      Based on measurements of serum erythropoietin and transferrin receptor, the
      distinction between marrow unresponsiveness to normal Epo stimulation and
      deficient Epo production is important for the treatment of the anemia of multiple
      myeloma with recombinant human Epo. Higher doses would probably be necessary if
      adequate Epo production is present, whereas only replacement therapy with lower
      doses may be sufficient when Epo production has been shown to be inappropriate.

PMID- 8528048
TI  - G-CSF in the biology and treatment of acute myeloid leukemias.
AB  - Granulocyte colony-stimulating factor (G-CSF) is an hemopoietic growth factor
      produced by fibroblasts, monocytes and endothelial cells. The role of G-CSF in
      the biology of acute myeloid leukemia (AML) has been investigated by several
      authors, who have demonstrated receptor mediated enhanced proliferation of AML
      blasts in vitro, in the presence of G-CSF. This effect is further increased by
      addition of other cytokines such as GM-CSF, IL3, IL4, Stem cell factor (SCF),
      while Tumor Necrosis Factor (TNF) and Transforming Growth Factor beta 1 (TGF beta
      1) seem to exert an inhibitory activity. An autocrine production of G-CSF by AML
      cells, a paracrine production by accessory cells and a protective effect
      displayed by G-CSF against programmed cell death could partially contribute to
      explain the pathogenesis of AML. In vivo, G-CSF has been used after chemotherapy
      in AML, in order to improve hemopoietic recovery in patients at high risk of
      infection. Current studies are focusing on better definition of the role of G
      CSF, as such or combined with other biological modifiers, in dose intensification
      and autologous bone marrow or peripheral blood stem cell transplantation.

PMID- 8528049
TI  - A role for ferritin in hematopoiesis and the immune system.
AB  - Elevated serum ferritin levels have been reported in a number of pathological
      states. These observations indicate that cells of the immune system can
      participate in the prevention of potential tissue toxicity from iron
      accumulation, and iron and iron-binding protein have important effects on immune
      systems. Ferritin is generally regarded as an intracellular iron storage protein.
      However, small amounts of ferritin circulate in the serum of normal individuals,
      and the physiological role of serum ferritin remains obscure. Although the
      function of ferritin is inevitably linked to iron metabolism, a role for ferritin
      in hematopoiesis and the immune system has drawn attention for years. Ferritin
      has an inhibitory effect on the in vitro growth of human hematopoietic progenitor
      cells and on the proliferation of T lymphocytes in vitro. Recently we report that
      ferritin may directly suppress the differentiation of human B lymphocytes
      maturing into antibody producing cells in vitro. In the present review, we
      summarise this field of research.

PMID- 8528050
TI  - Multidrug resistance (Mdr1) gene expression in peripheral blasts from patients
      with acute leukemia only rarely increases during disease progression after
      combination chemotherapy.
AB  - Multidrug resistance gene (mdr1) RNA levels were determined in 55, and P
      glycoprotein expression in 37 samples of peripheral leukemic cells from 17
      patients with acute myeloblastic leukemia (AML) and 7 patients with acute
      lymphocytic leukemia (ALL). Between sample collections, patients were treated
      with various chemotherapy regimens. Mdr1 RNA levels were quantified by a RNA-RNA
      solution hybridization assay. P-glycoprotein was determined by Western blot
      analysis. Samples from 14 patients (9 AML, 5 ALL) had undetectable mdr1 RNA
      levels at initial analysis. Only two of these had detectable levels after
      chemotherapy. Ten patients (8 AML, 2 ALL) had detectable mdr1 RNA levels at
      initial analysis (median 1.0 transcript per cell, range 0.2-1.4). Increase of
      mdr1 RNA levels after chemotherapy were observed in cells from 3 patients, one
      patient had a lower level after chemotherapy and the 6 remaining patients had
      essentially unchanged mdr1 RNA levels in their leukemic cells. Samples from 13
      patients were sequentially analysed for P-glycoprotein expression. In one
      patient, no P-glycoprotein was detectable at initial analysis but was weakly
      positive after chemotherapy. In the remaining 12 patients, P-glycoprotein levels
      stayed stable during disease progression. In conclusion, combination chemotherapy
      seems only rarely to be associated with an increase of mdr1 gene expression in
      residual leukemic cells. The addition of resistance modifiers to chemotherapy in
      order to overcome P-glycoprotein mediated resistance might therefore be more
      effective in chemotherapy naive patients since it is possible that during later
      disease progression additional mechanisms of resistance may be more operative.

PMID- 8528051
TI  - Identification of a novel receptor tyrosine kinase expressed in acute myeloid
      leukemic blasts.
AB  - Using the polymerase chain reaction with degenerate oligonucleotides derived from
      conserved motifs within the catalytic kinase domain of protein tyrosine kinases,
      and RNA extracted from embryonic stem cells, sequences that encode a segment of
      the kinase domain of several potentially novel receptor tyrosine kinases (RTKs)
      have been identified. One of these was selected for further study because in
      Northern analysis it hybridized to RNA from multipotential hematopoietic cell
      lines, but not from lines representative of lineage-committed cells. A cDNA for
      this receptor, designated developmental tyrosine kinase (DTK), was isolated and
      encodes a protein with structural similarities to AXL. Together these receptors
      form a new class of RTK. DTK is expressed in a number of human leukemic cell
      lines, and in the blasts of 6 of 11 patients with acute myeloid leukemia (AML)
      analyzed. The structure of DTK suggests that it may function as a cell adhesion
      molecule, and mediate cell-to-cell or cell-matrix interactions between
      hematopoietic cells and their respective microenvironments.

PMID- 8528052
TI  - Cytofluorimetric and functional analysis of c-kit receptor in acute leukemia.
AB  - The SR-1 monoclonal antibody (MoAb) recognizes an epitope of the c-kit receptor
      (KR), present on normal hemopoietic CD34+ stem cells as well as on blasts from
      patients with acute leukemia. Cytometric analysis by indirect immunofluorescence
      with the SR-1 MoAb was performed in 98 patients with acute myeloblastic leukemia
      (AML) and in 37 patients with acute lymphoblastic leukemia (ALL) in order to
      detect the presence of the KR and to examine its prognostic significance. Sixty
      nine of 98 (70%) AML patients were SR-1 positive independently of the FAB
      subtype, although a higher incidence of SR-1 positive cases was observed in M4
      and M5 AML and in those cases that also coexpressed lymphoid antigens. Fourteen
      AML samples were studied by Northern blot analysis and the KR mRNA was detected
      in the majority of SR-1 positive cases and also in 2 of 3 SR-1 negative samples.
      Furthermore, "in vitro" cultures from 15 cases showed that recombinant human Stem
      cell factor (rhSCF) induced an increased proliferative activity in most tested
      cases (11/15); this was further enhanced when rhSCF was combined with rhIL-3 +
      rhGM-CSF (p = 0.007) and with the GM-CSF/IL-3 fusion protein PIXY321 (p = 0.003).
      Thirty-seven ALL cases were also studied and all but one were SR-1 negative.
      Interestingly, the only SR-1 positive case also coexpressed myeloid antigens and
      showed an "in vitro" response when stimulated with rhSCF. Finally, the complete
      remission (CR) rate, survival and event-free survival were evaluated in 75 AML
      patients who received standard and identical chemotherapy; unlike previous
      studies which utilized a different anti-KR MoAb (YB5.B8) and which showed a poor
      prognosis for KR positive patients, we were unable to document any significant
      difference in CR rate, survival and event-free survival.

PMID- 8528053
TI  - Effects of long-term treatment with recombinant human granulocyte-macrophage
      colony-stimulating factor in patients with myelodysplastic syndrome.
AB  - We examined the effects of long-term treatment with recombinant human granulocyte
      macrophage colony-stimulating factor (rhGM-CSF) in 61 patients with
      myelodysplastic syndrome (MDS). Patients were randomly assigned to receive daily
      subcutaneous injection of 60 micrograms/m2, 125 micrograms/m2 or 250
      micrograms/m2 for 8 weeks. A significant increase in granulocyte counts including
      neutrophils and eosinophils was shown from one week after the start of the
      treatment in all three dose groups. The increase in granulocyte counts reached a
      plateau at the 4th week and was sustained during the treatment period. However,
      no consistent change in other cell lineages including monocytes, lymphocytes,
      reticulocytes and platelets were observed. Nevertheless peak-levels of these
      cells were significantly higher than the pre-treatment levels. In higher dose
      groups, the number of patients developing infections was reduced. There was no
      significant difference in the incidence of adverse events among the 3 dose
      groups, and the toxicity was generally well-tolerated. These observations
      indicate that treatment with rhGM-CSF can be of potential therapeutic benefit to
      patients with MDS.

PMID- 8528054
TI  - Low-dose cytosine arabinoside in patients with acute myeloid leukemia not
      eligible for standard chemotherapy.
AB  - The results of treatment with low dose cytosine arabinoside (LDARA-C) in 131 AML
      patients ineligible for standard regimens were analyzed retrospectively. Eighty
      seven were previously untreated, 25 were refractory to conventional chemotherapy
      and 19 were relapsed patients. The median age was 66 years (15-84). An antecedent
      hematological disorder (AHD) was documented in half of the patients. Overall, 22
      (17%) achieved complete remission, 14 (11%) partial remission, 77 (59%) had
      resistant leukemia and 18 died during induction. Median disease free survival was
      57 weeks and median survival, for the 87 previously untreated patients, was 22.5
      weeks. The prognostic value of initial parameters was analyzed for response. Bone
      marrow cellularity was the only significant factor. We observed 33% vs 81% (p <
      0.01) of responses in patients with normo-hypercellular and hypocellular marrow,
      respectively. Accordingly, there was a trend to more responses in patients with
      leukocyte counts of less than 10 x 10(9)/L. M4-M5 FAB subtypes were frequently
      resistant to LDARA-C, resulting in a lower response rate compared to M0-M2 (18%
      vs 32%). Other parameters, including age, sex, hemoglobin, platelet count, AHD
      and fever at diagnosis, had no prognostic value. Our findings suggest that LDARA
      C may be an effective treatment for some patients who are not eligible for first
      line conventional chemotherapy. However, this schedule is not advised in patients
      with monocytic leukemia or those with an hypercellular marrow.

PMID- 8528055
TI  - Relative roles of natural killer- and T cell-mediated anti-leukemia effects in
      chronic myelogenous leukemia patients treated with interferon-alpha.
AB  - Potential anti-leukemia effects mediated by T cells or by natural killer (NK)
      cells were investigated in chronic myelogenous leukemia (CML) patients treated
      with interferon-alpha. Therapy-associated modulation of T cell and NK reactivity
      was monitored for one year from initiation in autologous mixed lymphocyte-tumor
      cell reactions and cytotoxicity directed against autologous CML cells,
      respectively. During the course of IFN-therapy, NK activity against autologous
      CML cells increased steadily, whereas T cell reactivity fluctuated randomly.
      Despite the high level of T cell reactivity to autologous tumor cells in short
      term (6 days) culture, 1) they failed to respond to synthetic peptides
      corresponding to the bcr/abl fusion sequence of the patient, and 2) only one
      proliferative T cell clone (TCC) was isolated which specifically recognized HLA
      DR-matched CML cells. This TCC appeared not to recognize synthetic peptides
      corresponding to the bcr/abl fusion sequence of the patient; the antigen to which
      it responds remains unknown. To assess potential immunogenicity of bcr/abl
      peptides, it was attempted to sensitize T cells from normal donors in vitro. Of
      109 cell lines obtained from seven different donors, eleven showed peptide
      dependent proliferation. Therefore, although these results show that it is
      possible to isolate apparently CML-specific T cells from patients, as well as to
      prime T cells against tumor-specific peptide in vitro, the frequency of such T
      cell-mediated reactivity appears low and its relevance to anti-leukemic effects
      questionable. On the other hand, the strong time-dependent enhancement of natural
      killing of autologous CML blasts during IFN-alpha treatment, a phenomenon not
      observed for T cell reactivity, suggests that natural immunity may be more
      important in controlling disease.

PMID- 8528056
TI  - Glomerular injury in chronic myelomonocytic leukemia.
AB  - Among 825 cases of de novo myelodysplastic syndromes (MDS) diagnosed over a
      period of 13 years in our center, 4 had clinically significant glomerulopathy.
      All 4 fulfilled diagnostic criteria of chronic myelomonocytic leukemia (CMML),
      and could be classified in the low or intermediate risk groups according to two
      scoring systems. Presenting symptoms of renal involvement were edema in 3 cases
      and acute renal failure in the remaining patient. Three patients had the
      nephrotic syndrome. Renal biopsy (performed in 2 cases but considered as
      contraindicated in the other cases) showed AL amyloidosis on one case and
      extracapillary glomerulonephritis in the other case. The 4 patients were treated
      with V16 or hydroxyurea and two had renal improvement. Only one previous case of
      MDS associated with glomerulopathy has been reported before and also very
      probably had CMML. This, and the response of renal disease to chemotherapy in 2
      of our patients suggests a possible relationship between the two disorders. More
      systematic investigation of glomerular function, in CMML, could possibly disclose
      a higher incidence of cases of glomerular injury in this type of MDS.

PMID- 8528057
TI  - Clinical experience with fludarabine and its immunosuppressive effects in
      pretreated chronic lymphocytic leukemias and low-grade lymphomas.
AB  - Fludarabine monophosphate (FAMP) is a new adenine nucleoside analogue with a
      promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) and low-grade
      non-Hodgkin lymphomas (NHLs). Here, the clinical experience and side effects with
      FAMP are reported in 77 patients with pretreated CLL (59 B-CLL, 2 T-CLL) and low
      grade NHLs (9 immunocytic lymphomas including 5 Waldenstrom's macroglobulinaemia,
      2 centrocytic (cc) and 5 centroblastic-centrocytic (cb-cc) NHLs). 70/77 patients
      are evaluable for response. All except 8 patients were pretreated with one to
      four different regimens and had progressive disease. FAMP was administered at a
      dosage of 25 mg/m2 daily for 5 days as 30 minute infusion every fifth week.
      Partial (PR) or complete remission (CR) was achieved in 38/56 (68%) and 3/56 (5%)
      of evaluable patients with CLL, respectively. In 7/8 (1 x CR, 6 x PR) evaluable
      patients with immunocytic lymphoma and in 3/6 (3 x PR) patients with cc or cb-cc
      lymphoma remissions were obtained. The probability of progression-free survival
      was 66% and the event-free survival was 25% and 22% at 12 and 18 months. The
      median progression-free survival until relapse or death, however, was only 7
      months (2-20+). Major toxic effects included infections in 22 patients (grade 3
      and 4 WHO), granulocytopenia (mainly grade 3) and nausea in 8 patients (mainly
      grade 1). 19/22 patients were in PR at the time of occurrence of infectious
      complications. Meanwhile, 14 patients died due to septicaemia, pneumonia or other
      infections. Nine patients developed severe septicaemia, 4 patients had
      pneumocystis carinii or aspergillus pneumonias. The high infection rate may not
      only be due to hypogammaglobulinaemia and granulocytopenia induced by FAMP but
      also to a remarkable decrease of CD4+ cells from a median of 2479 to 241 CD4+
      cells/microliters after 6 cycles of FAMP. In one case a tumor lysis syndrome was
      observed. No CNS toxicity was noted. It is concluded that FAMP is effective even
      in patients with advanced CLL and low-grade NHLs refractory to multiple
      chemotherapy regimens. However, FAMP has a marked suppressive effect on
      granulocytes and T-lymphocytes, predominantly CD4+ lymphocytes.

PMID- 8528058
TI  - Survival of young patients with chronic lymphocytic leukemia failing fludarabine
      therapy: a basis for the use of myeloablative therapies.
AB  - We examined the survival of 91 young patients (< or = 55 years) with chronic
      lymphocytic leukemia from the time of failure of fludarabine therapy, in an
      attempt to identify those with a poor outcome who may benefit from investigative
      dose-intensive therapies. The median survival of patients unresponsive to
      fludarabine (n = 42) was 48 weeks, and only 11% responded to subsequent
      therapies. The median survival of patients relapsing following a fludarabine
      induced remission (n = 49) was 87 weeks, and 83% of those who had received
      fludarabine as their first therapy (n = 14) responded to further fludarabine
      containing therapies, with 60% alive at four years. Only 7% of those relapsing
      patients who had received fludarabine as salvage therapy (n = 35) responded to
      subsequent therapies (median survival 72 weeks). The poor outlook for these
      patients justifies the consideration of innovative dose-intensive therapies, such
      as bone marrow transplantation, with their attendant risk of toxicity.

PMID- 8528059
TI  - The retinoblastoma gene (RB-1) status in multiple myeloma: a report on 35 cases.
AB  - We looked for abnormalities of the retinoblastoma (RB-1) gene and of RB protein
      expression in 35 patients with multiple myeloma (MM). Mutations in exons 20 to 24
      of the RB-1 gene (exons where mutations predominate in retinoblastoma and other
      solid tumors) were analyzed by single stranded conformation polymorphism (SSCP).
      RB-1 protein was studied in bone marrow plasma cells by immunocytochemistry (ABC
      peroxidase technique) with a specific monoclonal antibody. Southern blot analysis
      of RB-1 gene was also performed in 20 of the patients. Twenty two patients
      analyzed had advanced disease (stage III or, in one case, plasma cell leukemia)
      and cytogenetic analysis (performed in 31 cases) found monosomy 13 in 9 patients.
      No rearrangement of the RB-1 gene was found by Southern analysis. Absent or
      greatly reduced RB-1 protein level was found in plasma cells in 4 of the patients
      (11%), whereas normal levels were seen in the remaining cases. No point mutation
      in exons 20 to 24 and their flanking introns were found in any of the 35
      patients. Three of the 4 patients with absent or reduced RB-1 protein expression
      had advanced MM (stage III: 2 cases; plasma cell leukemia: 1 case); all 4
      patients were resistant to treatment (as compared to 7 of the 31 patients with
      normal RB-1 protein levels); only one of them was subsequently found to have
      monosomy 13 (as compared to 9 of the 28 other karyotyped patients). Our findings
      suggest that abnormalities of the RB-1 gene and its expression are rare in MM.
      Absent or reduced expression of RB-1 protein was not significantly correlated to
      monosomy 13 and was not associated with gross rearrangements of the RB-1 gene by
      Southern analysis or point mutations in exons 20 to 24 of the gene. Reduced
      expression of RB-1 protein may be associated with advanced disease and poor
      response to treatment, although larger numbers of patients will be required for
      more adequate conclusions.

PMID- 8528060
TI  - Treatment of young relapsed Hodgkin's disease patients with high-dose
      chemotherapy followed by peripheral blood stem cell transplantation.
AB  - Four patients less than 20 years of age with Hodgkin's disease, who had developed
      either second or third relapse, were treated with high-dose chemotherapy followed
      by peripheral blood stem cell transplantation (PBSCT). Peripheral blood stem
      cells (PBSC) were collected after the administration of high-dose cytosine
      arabinoside (HD-AraC, 1g/m2 x 4). The conditioning regimen for PBSCT contained
      cyclophosphamide (50mg/m2 x 4), etoposide (150mg/m2 x 6) and ranimustine
      (250mg/dose x 1) (CVM regimen). A significant tumor regression was thus obtained
      after HD-AraC in 3 cases. The amount of PBSC harvested ranged from 1.2 to 4.5 x
      10(5)/kg CFU-GM. Several cycles of conventional therapy were performed prior to
      the transplantation. PBSCT was done only after achieving a complete remission
      (CR) in 3 cases, but during relapse in another case. All patients showed both a
      rapid and sustained hematological recovery without any critical side effects.
      After this treatment, the 3 patients who were in CR at transplantation maintained
      a CR for 27, 26, and 4 months, respectively, while another developed a bone
      relapse despite achieving a CR by PBSCT. These results suggest that a combination
      of HD-AraC and CVM followed by PBSCT is therefore considered to be beneficial in
      the treatment of relapsed Hodgkin's disease.

PMID- 8528061
TI  - Activation of MYCN in a case of non-Hodgkin's lymphoma.
AB  - We have examined a series of non-Hodgkin's lymphomas (NHL) for evidence of
      expression of the MYC gene family. Northern blot analysis of RNA samples derived
      from 11 non-malignant reactive lymphoid tissues and 33 NHL was used to
      investigate expression of MYC, MYCL and MYCN. As expected MYC expression was
      detected in all samples. The levels of MYC expression were quantified by
      densitometry and appeared to be 3-8 fold higher in high grade NHL than in the low
      grade NHL or non-malignant lymphoid tissue. No expression of MYCL was detected in
      any sample. Expression of MYCN was however observed in one sample, which had been
      diagnosed as a T-cell high grade NHL. A detailed cytogenetic analysis of this
      sample proved difficult to obtain but, by using fluorescence in-situ
      hybridization (FISH), we were able to demonstrate that on one of the chromosomes
      2 the MYCN gene was localised to a translocation breakpoint region. It therefore
      appears that in NHL it is possible for MYCN, like MYC in Burkitt lymphoma, to be
      activated as a result of a chromosome translocation event.

PMID- 8528062
TI  - Expression of multidrug resistant gene (mdr-1/P-glycoprotein) in a
      megakaryoblastic cell line, CMK, and its enhancement during megakaryocytic
      differentiation.
AB  - Multidrug resistance is a severe clinical problem in the chemotherapy of
      malignant disease. Acute megakaryoblastic leukemia (AMKL) is a rare form of
      childhood leukemia, and is often resistant to many anti-cancer chemotherapeutic
      drugs. Here we report the expression of the mdr-1/P-glycoprotein in a cell line,
      CMK, established from a patient with AMKL. Expression of mdr-1 mRNA in CMK11-5
      cells, a well differentiated subline, was higher than in CMK6 cells, a poorly
      differentiated subline. The level of P-glycoprotein was also higher in CMK11-5
      cells. The cytokines interferon-gamma (IFN-gamma), GM-CSF and IL-3, which were
      shown to induce megakaryocytic differentiation of CMK cells, enhanced the
      expression of the mdr-1 mRNA and levels of P-glycoprotein. These results imply
      that differentiated megakaryocytic cells may have higher levels of the P
      glycoprotein expression, suggesting a possible normal physiological function of P
      glycoprotein in mature megakaryocytes.

PMID- 8528063
TI  - Immunoblastic transformation of a Sezary syndrome in a black Caribbean patient
      without evidence of HTLV-I.
AB  - We describe an unusual case of Sezary syndrome which transformed into a large T
      cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent
      with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis
      using sensitive techniques. The disease presented as a small-cell Sezary syndrome
      and transformed in an inguinal lymph node one year from diagnosis. Immunological
      markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8-
      with expression of T-cell activation markers and a high proliferative rate.
      Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in
      the peripheral blood and immunoblasts in the lymph node. Cytogenetics
      demonstrated complex clonal chromosome abnormalities with involvement of 7q35,
      the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis
      showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph
      node and peripheral blood cells. Antibodies to HTLV-I were not detected in the
      serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were
      demonstrated by nested polymerase chain reaction with primers to the envelope
      proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The
      disease had an aggressive course and was refractory to therapy; the patient died
      of progressive disease 28 months from presentation. Two unusual features
      characterised this patient's illness: immunoblastic transformation of a Sezary
      syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA
      sequences and negative HTLV-I serology and the atypical lymph node histology
      resembling ATLL.

PMID- 8528064
TI  - Teaching cases from the Royal Marsden Hospital. Case 9: an elderly patient with
      unusual circulating cells.

PMID- 8528065
TI  - Hyaluronidases--a group of neglected enzymes.
AB  - Hyaluronan is an important constituent of the extracellular matrix. This
      polysaccharide can be hydrolyzed by various hyaluronidases that are widely
      distributed in nature. The structure of some bacterial and animal enzymes of this
      type has recently been elucidated. It could be shown that the hyaluronidases from
      bee and hornet venom and the PH-20 hyaluronidase present on mammalian spermatozoa
      are homologous proteins.

PMID- 8528066
TI  - Predicting the structure of the light-harvesting complex II of Rhodospirillum
      molischianum.
AB  - We attempted to predict through computer modeling the structure of the light
      harvesting complex II (LH-II) of Rhodospirillum molischianum, before the
      impending publication of the structure of a homologous protein solved by means of
      X-ray diffraction. The protein studied is an integral membrane protein of 16
      independent polypeptides, 8 alpha-apoproteins and 8 beta-apoproteins, which
      aggregate and bind to 24 bacteriochlorophyll-a's and 12 lycopenes. Available
      diffraction data of a crystal of the protein, which could not be phased due to a
      lack of heavy metal derivatives, served to test the predicted structure, guiding
      the search. In order to determine the secondary structure, hydropathy analysis
      was performed to identify the putative transmembrane segments and multiple
      sequence alignment propensity analyses were used to pinpoint the exact sites of
      the 20-residue-long transmembrane segment and the 4-residue-long terminal
      sequence at both ends, which were independently verified and improved by homology
      modeling. A consensus assignment for the secondary structure was derived from a
      combination of all the prediction methods used. Three-dimensional structures for
      the alpha- and the beta-apoprotein were built by comparative modeling. The
      resulting tertiary structures are combined, using X-PLOR, into an alpha beta
      dimer pair with bacteriochlorophyll-a's attached under constraints provided by
      site-directed mutagenesis and spectral data. The alpha beta dimer pairs were then
      aggregated into a quaternary structure through further molecular dynamics
      simulations and energy minimization. The structure of LH-II so determined is an
      octamer of alpha beta heterodimers forming a ring with a diameter of 70 A.

PMID- 8528067
TI  - Synthesis, activity, and preliminary structure of the fourth EGF-like domain of
      thrombomodulin.
AB  - The fourth EGF-like domain of thrombomodulin (TM4), residues E346-F389 in the TM
      sequence, has been synthesized. Refolding of the synthetic product under redox
      conditions gave a single major product. The disulfide bonding pattern of the
      folded, oxidized domain was (1-3, 2-4, 5-6), which is the same as that found in
      EGF protein. TM4 was tested for TM anticoagulant activity because deletion and
      substitution mutagenesis experiments have shown that the fourth EGF-like domain
      of TM is essential for TM cofactor activity. TM4 showed no TM-like activity in
      two assay systems, both for inhibition of fibrin clot formation, and for cofactor
      activity in thrombin activation of protein C. A preliminary structure of TM4 was
      determined by 2D 1H NMR from 519 NOE-derived distance constraints. Distance
      geometry calculations yielded a single convergent structure. The structure
      resembles the structure of EGF and other known EGF-like domains but has some key
      differences. The central two-stranded beta-sheet is conserved despite the
      differences in the number of amino acids in the loops. The C-terminal loop formed
      by the disulfide bond between C372 and C386 in TM4 is five amino acids longer
      than the analogous loop between C33 and C42 of EGF protein. This loop appears to
      have a different fold in TM4 than in EGF protein. The loop forms the two outside
      strands of a broken, irregular tri-stranded beta-sheet, and amino acids H384-F389
      lie between the two strands forming the middle strand of the sheet. Thus,
      although the C-terminus of EGF protein forms one of the outside strands of a tri
      stranded antiparallel sheet, the C-terminus of TM4 forms the inside strand of an
      irregular tri-stranded parallel-anti-parallel sheet. The residues D349, E357, and
      E374, which were shown to be critical for cofactor activity by alanine scanning
      mutagenesis, all lie in a patch near the C-terminal loop, and are solvent
      accessible. The other critical residues, Y358 and F376, are largely buried and
      appear to play essential structural rather than functional roles.

PMID- 8528068
TI  - Modeled structure of the 75-kDa neurotrophin receptor.
AB  - Motifs in ligand-binding domains of the neurotrophin (NTR) and lymphotoxin (TNFR
      I) receptors define a family of receptors that mediates programmed cell death. We
      have explored relationships of architecture and function in this family through a
      molecular model of NTR, also called p75NGFR or LANR. Modeling by homology took
      advantage of four modular subdomains in the crystal structure of TNFR-I that also
      occur in NTR. Hypothetical complexes between the model and a ligand structure
      (for nerve growth factor, NGF) were then examined using docking software. NTR
      appears to bind in the dimer interface of NGF, making two sets of contacts. NTR
      subdomains III and IV provide the ligand-contact surfaces, in contrast to TNFR,
      in which subdomains II and III contact TNF-beta. NTR subdomain II appears to have
      been evolutionarily modified, potentially contributing to an interface between
      receptor subunits. These and other specific predictions of the model will require
      experimental confirmation.

PMID- 8528069
TI  - Molecular modeling of a T-cell receptor bound to a major histocompatibility
      complex molecule: implications for T-cell recognition.
AB  - The main functions of the T-cell receptor (TCR) involve its specific interaction
      with short and linear antigenic peptides bound to the major histocompatibility
      complex (MHC) molecules. In the absence of a 3D structure for TCR and for the
      TCR/peptide/MHC complex, several attempts to characterize the structural
      components of the TCR/peptide/MHC interaction have been made. However, this
      subject is still troublesome. In this paper a computer-based 3D model for a
      TCR/peptide/MHC complex (5C.C7/moth cytochrome c [MCC] peptide 93-103/I-Ek) was
      obtained. The complex surface shows a high complementarity between the 5C.C7
      structure and the peptide/I-Ek molecule. The mapping of residues involved in the
      TCR/peptide/MHC interaction shows close agreement with mutational experiments
      (Jorgensen JL, Reay PA, Ehrich EW, Davis MM, 1992b, Annu Rev Immunol 10:835-873).
      Moreover, the results are consistent with a recent variability analysis of TCR
      sequences using three variability indexes (Almagro JC, Zenteno-Cuevas R, Vargas
      Madrazo E, Lara-Ochoa F, 1995b, Int J Pept Protein Res 45:180-186). Accordingly,
      the 3D model of the 5C.C7/MCC peptide 93-103/I-Ek complex provides a framework to
      generate testable hypotheses about TCR recognition. Thus, starting from this
      model, the role played by each loop that forms the peptide/MHC binding site of
      the TCR is discussed.

PMID- 8528071
TI  - The structure of human pancreatic alpha-amylase at 1.8 A resolution and
      comparisons with related enzymes.
AB  - The structure of human pancreatic alpha-amylase has been determined to 1.8 A
      resolution using X-ray diffraction techniques. This enzyme is found to be
      composed of three structural domains. The largest is Domain A (residues 1-99, 169
      404), which forms a central eight-stranded parallel beta-barrel, to one end of
      which are located the active site residues Asp 197, Glu 233, and Asp 300. Also
      found in this vicinity is a bound chloride ion that forms ligand interactions to
      Arg 195, Asn 298, and Arg 337. Domain B is the smallest (residues 100-168) and
      serves to form a calcium binding site against the wall of the beta-barrel of
      Domain A. Protein groups making ligand interactions to this calcium include Asn
      100, Arg 158, Asp 167, and His 201. Domain C (residues 405-496) is made up of
      anti-parallel beta-structure and is only loosely associated with Domains A and B.
      It is notable that the N-terminal glutamine residue of human pancreatic alpha
      amylase undergoes a posttranslational modification to form a stable pyrrolidone
      derivative that may provide protection against other digestive enzymes. Structure
      based comparisons of human pancreatic alpha-amylase with functionally related
      enzymes serve to emphasize three points. Firstly, despite this approach
      facilitating primary sequence alignments with respect to the numerous insertions
      and deletions present, overall there is only approximately 15% sequence homology
      between the mammalian and fungal alpha-amylases. Secondly, in contrast, these
      same studies indicate that significant structural homology is present and of the
      order of approximately 70%. Thirdly, the positioning of Domain C can vary
      considerably between alpha-amylases. In terms of the more closely related porcine
      enzyme, there are four regions of polypeptide chain (residues 237-250, 304-310,
      346-354, and 458-461) with significantly different conformations from those in
      human pancreatic alpha-amylase. At least two of these could play a role in
      observed differential substrate and cleavage pattern specificities between these
      enzymes. Similarly, amino acid differences between human pancreatic and salivary
      alpha-amylases have been localized and a number of these occur in the vicinity of
      the active site.

PMID- 8528070
TI  - The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic
      resonance and circular dichroism.
AB  - The heat-stable enterotoxin b (STb) is secreted by enterotoxigenic Escherichia
      coli that cause secretory diarrhea in animals and humans. It is a 48-amino acid
      peptide containing two disulfide bridges, between residues 10 and 48 and 21 and
      36, which are crucial for its biological activity. Here, we report the solution
      structure of STb determined by two- and three-dimensional NMR methods.
      Approximate interproton distances derived from NOE data were used to construct
      structures of STb using distance-geometry and simulated annealing procedures. The
      NMR-derived structure shows that STb is helical between residues 10 and 22 and
      residues 38 and 44. The helical structure in the region 10-22 is amphipathic and
      exposes several polar residues to the solvent, some of which have been shown to
      be important in determining the toxicity of STb. The hydrophobic residues on the
      opposite face of this helix make contacts with the hydrophobic residues of the C
      terminal helix. The loop region between residues 21 and 36 has another cluster of
      hydrophobic residues and exposes Arg 29 and Asp 30, which have been shown to be
      important for intestinal secretory activity. CD studies show that reduction of
      disulfide bridges results in a dramatic loss of structure, which correlates with
      loss of function. Reduced STb adopts a predominantly random-coil conformation.
      Chromatographic measurements of concentrations of native, fully reduced, and
      single-disulfide species in equilibrium mixtures of STb in redox buffers indicate
      that the formation of the two disulfide bonds in STb is only moderately
      cooperative. Similar measurements in the presence of 8 M urea suggest that the
      native secondary structure significantly stabilizes the disulfide bonds.

PMID- 8528072
TI  - The use of natural and unnatural amino acid substrates to define the substrate
      specificity differences of Escherichia coli aspartate and tyrosine
      aminotransferases.
AB  - The tyrosine (eTATase) and aspartate (eAATase) aminotransferases of Escherichia
      coli transaminate diacarboxylic amino acids with similar rate constants. However,
      eTATase exhibits approximately 10(2)-10(4)-fold higher second-order rate
      constants for the transamination of aromatic amino acids than does eAATase. A
      series of natural and unnatural amino acid substrates was used to quantitate
      specificity differences for these two highly related enzymes. A general trend
      toward lower transamination activity with increasing side-chain length (extending
      from aspartate to glutamate to alpha-aminoadipate) is observed for both enzymes.
      This result suggests that dicarboxylate ligands associate with the two highly
      related enzymes in a similar manner. The high reactivity of the enzymes with L
      Asp and L-Glu can be attributed to an ion pair interaction between the side-chain
      carboxylate of the amino acid substrate and the guanidino group of the active
      site residue Arg 292 that is common to both enzymes. A strong linear correlation
      between side-chain hydrophobicity and transamination rate constants obtains for n
      alkyl side-chain amino substrates with eTATase, but not for eAATase. The present
      kinetic data support a model in which eAATase contains one binding mode for all
      classes of substrate, whereas the active site of eTATase allows an additional
      mode that has increased affinity for hydrophobic amino acid.

PMID- 8528073
TI  - Redesign of the substrate specificity of Escherichia coli aspartate
      aminotransferase to that of Escherichia coli tyrosine aminotransferase by
      homology modeling and site-directed mutagenesis.
AB  - Although several high-resolution X-ray crystallographic structures have been
      determined for Escherichia coli aspartate aminotransferase (eAATase), efforts to
      crystallize E. coli tyrosine aminotransferase (eTATase) have been unsuccessful.
      Sequence alignment analyses of eTATase and eAATase show 43% sequence identity and
      72% sequence similarity, allowing for conservative substitutions. The high
      similarity of the two sequences indicates that both enzymes must have similar
      secondary and tertiary structures. Six active site residues of eAATase were
      targeted by homology modeling as being important for aromatic amino acid
      reactivity with eTATase. Two of these positions (Thr 109 and Asn 297) are
      invariant in all known aspartate aminotransferase enzymes, but differ in eTATase
      (Ser 109 and Ser 297). The other four positions (Val 39, Lys 41, Thr 47, and Asn
      69) line the active site pocket of eAATase and are replaced by amino acids with
      more hydrophobic side chains in eTATase (Leu 39, Tyr 41, Ile 47, and Leu 69).
      These six positions in eAATase were mutated by site-directed mutagenesis to the
      corresponding amino acids found in eTATase in an attempt to redesign the
      substrate specificity of eAATase to that of eTATase. Five combinations of the
      individual mutations were obtained from mutagenesis reactions. The redesigned
      eAATase mutant containing all six mutations (Hex) displays second-order rate
      constants for the transamination of aspartate and phenylalanine that are within
      an order of magnitude of those observed for eTATase. Thus, the reactivity of
      eAATase with phenylalanine was increased by over three orders of magnitude
      without sacrificing the high transamination activity with aspartate observed for
      both enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528074
TI  - Structure and function of microplasminogen: I. Methionine shuffling, chemical
      proteolysis, and proenzyme activation.
AB  - We have cloned and expressed microplasminogen (mPlg), consisting of the N
      terminal undecapeptide of human glu-Plg spliced to its proenzyme domain. This
      truncated (approximately 28 kDa) proenzyme retained the distinctive catalytic
      activities of the larger parent. Replacement of M residues followed by M
      shuffling permitted subsequent scission by site-directed chemical proteolysis (in
      CNBr/formic acid) without impairing any of the protein's characteristic
      properties. Activation of chymotrypsinogen-related zymogens occurs by limited
      proteolysis; the newly liberated, highly conserved N-terminus (VVGG) forms a salt
      bridge with an aspartyl residue immediately upstream of the active site serine.
      The role of both of these elements in mPlg activation was probed using protein
      engineering and site-directed proteolysis to alter the length and amino acid
      composition of the N-terminus, and to replace the aspartate. All modifications
      affected both Km and Kcat. The results identify some structural parameters of the
      N-terminus required for proenzyme activation.

PMID- 8528075
TI  - Structure and function of microplasminogen: II. Determinants of activation by
      urokinase and by the bacterial activator streptokinase.
AB  - We have used a group of human microplasminogens (mPlg), modified by residue
      substitutions, insertions, deletions, and chain breaks (1) to study the
      determinants of productive interactions with two plasminogen activators,
      urokinase (uPA), and streptokinase (SK); (2) to explore the basis of species
      specificity in the zymogen-SK complex activity; and (3) to compare active SK
      complex formation in mPlg and microplasmin (mPlm). Modifications within the
      disulfide-bonded loop containing the activation site and the adjacent
      hexadecapeptide upstream sequence showed that uPA recognition elements
      encompassed R29 at the activation site and multiple elements extending upstream
      to perhaps 13 residues, all maintained in specific conformational register by
      surrounding pairs of disulfide bonds. A generally parallel pattern of structural
      requirements was observed for active zymogen-SK complex formation. Changes within
      the loop downstream of the activation site were tolerated well by uPA and poorly
      by SK. The introduction of selected short bovine (Plg) sequences in human mPlg
      reduced the activity of the resulting SK complexes. The requirements for active
      SK complex formation are different for mPlg and mPlm.

PMID- 8528076
TI  - Exhaustive enumeration of protein conformations using experimental restraints.
AB  - We present an efficient new algorithm that enumerates all possible conformations
      of a protein that satisfy a given set of distance restraints. Rapid growth of all
      possible self-avoiding conformations on the diamond lattice provides construction
      of alpha-carbon representations of a protein fold. We investigated the dependence
      of the number of conformations on pairwise distance restraints for the proteins
      crambin, pancreatic trypsin inhibitor, and ubiquitin. Knowledge of between one
      and two contacts per monomer is shown to be sufficient to restrict the number of
      candidate structures to approximately 1,000 conformations. Pairwise RMS
      deviations of atomic position comparisons between pairs of these 1,000 structures
      revealed that these conformations can be grouped into about 25 families of
      structures. These results suggest a new approach to assessing alternative protein
      folds given a very limited number of distance restraints. Such restraints are
      available from several experimental techniques such as NMR, NOESY, energy
      transfer fluorescence spectroscopy, and crosslinking experiments. This work
      focuses on exhaustive enumeration of protein structures with emphasis on the
      possible use of NOESY-determined distance restraints.

PMID- 8528077
TI  - The activation pathway of procarboxypeptidase B from porcine pancreas:
      participation of the active enzyme in the proteolytic processing.
AB  - The activation process of porcine pancreatic procarboxypeptidase B (pro-CPB) has
      been studied in detail by a number of complementary methodologies, and a
      description of the molecular events that lead to the generation of active
      carboxypeptidase B (CPB) has been deduced. The generated CPB participates in the
      degradation of its own activation segment by excising C-terminal residues from
      fragments produced by tryptic proteolysis. The trimming action of CPB is,
      however, not essential for the release of a fully functional enzyme, in contrast
      to what was previously reported for porcine procarboxypeptidase A (pro-CPA). In
      the model presented here, the activation process is solely dependent on the first
      tryptic cleavage, at the limit between the activation segment and the enzyme
      region, and the former piece loses all of its inhibitory capacity once severed
      from the proenzyme. The use of heterologous inhibitors of CPB activity during the
      study of the tryptic activation process of pro-CPB has been required for the
      capture of short-lived, otherwise nondetectable, intermediates. This has allowed
      a complete description of the process and shown that the first proteolytic action
      of trypsin can also take place on a second target bond. Structural considerations
      that take into account the three-dimensional structures of the A and B forms of
      the proenzymes lead us to propose that the differences in conformation at the
      region that connects the globular activation domain to the enzyme are the main
      responsible elements for the differences observed in the activation processes of
      both proenzymes.

PMID- 8528078
TI  - 1H, 15N, and 13C backbone chemical shift assignments, secondary structure, and
      magnesium-binding characteristics of the Bacillus subtilis response regulator,
      Spo0F, determined by heteronuclear high-resolution NMR.
AB  - Spo0F, sporulation stage 0 F protein, a 124-residue protein responsible, in part,
      for regulating the transition of Bacillus subtilis from a vegetative state to a
      dormant endospore, has been studied by high-resolution NMR. The 1H, 15N, and 13C
      chemical shift assignments for the backbone residues have been determined from
      analyses of 3D spectra, 15N TOCSY-HSQC, 15N NOESY-HSQC, HNCA, and HN(CO)CA.
      Assignments for many sidechain proton resonances are also reported. The secondary
      structure, inferred from short- and medium-range NOEs, 3JHN alpha coupling
      constants, and hydrogen exchange patterns, define a topology consistent with a
      doubly wound (alpha/beta)5 fold. Interestingly, comparison of the secondary
      structure of Spo0F to the structure of the Escherichia coli response regulator,
      chemotaxis Y protein (CheY) (Volz K, Matsumura P, 1991, J Biol Chem 266:15511
      15519; Bruix M et al., 1993, Eur J Biochem 215:573-585), show differences in the
      relative length of secondary structure elements that map onto a single face of
      the tertiary structure of CheY. This surface may define a region of binding
      specificity for response regulators. Magnesium titration of Spo0F, followed by
      amide chemical shift changes, gives an equilibrium dissociation constant of 20 +/
      5 mM. Amide resonances most perturbed by magnesium binding are near the putative
      site of phosphorylation, Asp 54.

PMID- 8528079
TI  - Interactions in nonnative and truncated forms of staphylococcal nuclease as
      indicated by mutational free energy changes.
AB  - Several mixed disulfide variants of staphylococcal nuclease have been produced by
      disulfide bond formation between nuclease V23C and methane, ethane, 1-propane, 1
      n-butane, and 1-n-pentane thiols. Although CD spectroscopy shows that the native
      state is largely unperturbed, the stability toward urea-induced unfolding is
      highly dependent on the nature of the group at this position, with the methyl
      disulfide protein being the most stable. The variant produced by modification
      with iodoacetic acid, however, gives a CD spectrum indicative of an unfolded
      polypeptide. Thiol-disulfide exchange equilibrium constants between nuclease V23C
      and 2-hydroxyethyl disulfide have been measured as a function of urea
      concentration. Because thiol-disulfide exchange and unfolding are
      thermodynamically linked, the effects of a mutation (disulfide exchange) can be
      partitioned between various conformational states. In the case of unmodified V23C
      and the 2-hydroxyethyl protein mixed disulfide, significant effects in the
      nonnative states of nuclease are observed. Truncated forms of staphylococcal
      nuclease are thought to be partially folded and may be good models for early
      folding intermediates. We have characterized a truncated form of nuclease
      comprised of residues 1-135 with a V23C mutation after chemical modification of
      the cysteine residue. High-resolution size-exclusion chromatography indicates
      that modification brings about significant changes in the Stokes radius of the
      protein, and CD spectroscopy indicates considerable differences in the amount of
      secondary structure present. Measurement of the disulfide exchange equilibrium
      constant between this truncated protein and 2-hydroxyethyl disulfide indicate
      significant interactions between position 23 and the rest of the protein when the
      urea concentration is lower than 1.5 M.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528080
TI  - A novel adenosine triphosphate analog with a heavy atom to target the nucleotide
      binding site of proteins.
AB  - We have synthesized 2'-deoxy-2'-iodoadenosine-5'-triphosphate (2'-IATP), a heavy
      atom analog of adenosine-5'-triphosphate. This compound was made for X-ray
      structural studies to target the nucleotide site of ATP binding proteins. It was
      diffused successfully into crystals of the microtubule-based motor proteins ncd
      (non-claret disjunctional protein from Drosophila melanogaster) and kinesin. With
      ncd, the nucleotide binding site was 70% occupied and the crystals were able to
      diffract X-rays to 2.5 A. The iodo-analog provided a useful isomorphous
      derivative with overall phasing power 1.89 in the range of 25.0-2.5 A. With
      kinesin, 2'-IATP co-crystallized with the protein. The crystals diffracted to at
      least 2.8 A with a phasing power of 1.73 in the range of 20.0-5.0 A. The analog
      was also found to be a substrate for all of the enzymes tested, including
      creatine kinase, pyruvate kinase, hexokinase, and myosin, with values of Km and
      Vmax that were within a factor of 10 of those for ATP. The analog supported
      muscle contraction, relaxing fibers, and producing active tension with values not
      statistically different from those obtained with ATP. These results all suggest
      that this analog should be useful for providing a heavy-atom derivative for
      crystals of enzymes that bind ATP.

PMID- 8528081
TI  - UME6, a negative regulator of meiosis in Saccharomyces cerevisiae, contains a C
      terminal Zn2Cys6 binuclear cluster that binds the URS1 DNA sequence in a zinc
      dependent manner.
AB  - UME6 is a protein of 836 amino acids from Saccharomyces cerevisiae that acts as a
      repressor and activator of several early meiotic genes. UME6 contains, near the C
      terminus, the amino acid sequence-771C-X2-C-X6-C-X6-C-X2-C-X6-C-, in which the
      spacings of the six Cys residues are identical to those found in 39 N-terminal
      Cys-rich DNA binding subdomains of fungal transcription factors. This sequence
      has been shown in GAL4 and other proteins to form a zinc binuclear cluster. In
      spite of the different location, the C-rich sequence, cloned and over-produced
      within the last 111 amino acid residues of UME6, UME6(111), forms a binuclear
      cluster and exhibits a Zn-dependent binding to the URS1 DNA sequence. The latter,
      TAGCCGCCGA, is required for the repression or activation of meiosis-specific
      genes by UME6. UME6(111) contains 1.8 +/- 0.4 mol Zn/mol protein and the Zn can
      be exchanged for Cd to yield a protein containing 1.9 +/- 0.1 mol Cd/mol protein.
      At 5 degrees C, 113Cd2UME6(111) shows two 113Cd NMR signals, with chemical shifts
      of 699 and 689 ppm, similar to those observed for 113Cd2GAL4(149). The magnitude
      of these chemical shifts suggests that each 113Cd nucleus is coordinated to four 
      S- ligands, compatible with a 113Cd2 cluster structure in which two thiolates
      from bridging ligands. The entire UME6 gene has been cloned and overexpressed and
      binds more tightly to the URS1 sequence than the zinc binuclear cluster domain
      alone. DNase I footprints of UME6 on URS1-containing DNA show that the protein
      protects the phosphodiesters of the 5'-CCGCCG-3' region within the URS1 sequence.

PMID- 8528082
TI  - The role of aspartate-235 in the binding of cations to an artificial cavity at
      the radical site of cytochrome c peroxidase.
AB  - The activated state of cytochrome c peroxidase, compound ES, contains a cation
      radical on the Trp-191 side chain. We recently reported that replacing this
      tryptophan with glycine creates a buried cavity at the active site that contains
      ordered solvent and that will specifically bind substituted imidazoles in their
      protonated cationic forms (Fitzgerald MM, Churchill MJ, McRee DE, Goodin DB,
      1994, Biochemistry 33:3807-3818). Proposals that a nearby carboxylate, Asp-235,
      and competing monovalent cations should modulate the affinity of the W191G cavity
      for ligand binding are addressed in this study. Competitive binding titrations of
      the imidazolium ion to W191G as a function of [K+] show that potassium competes
      weakly with the binding of imidazoles. The dissociation constant observed for
      potassium binding (18 mM) is more than 3,000-fold higher than that for 1,2
      dimethylimidazole (5.5 microM) in the absence of competing cations.
      Significantly, the W191G-D235N double mutant shows no evidence for binding
      imidazoles in their cationic or neutral forms, even though the structure of the
      cavity remains largely unperturbed by replacement of the carboxylate. Refined
      crystallographic B-values of solvent positions indicate that the weakly bound
      potassium in W191G is significantly depopulated in the double mutant. These
      results demonstrate that the buried negative charge of Asp-235 is an essential
      feature of the cation binding determinant and indicate that this carboxylate
      plays a critical role in stabilizing the formation of the Trp-191 radical cation.

PMID- 8528083
TI  - Evidence from sequence information that the interleukin-1 receptor is a
      transmembrane GTPase.
AB  - Evidence is presented that the cytoplasmic domain of the type I interleukin-1
      receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic
      amino acids that suggest a structural relatedness to the ras protooncogene
      protein and other members of the GTPase superfamily, despite a lack of
      significant detectable sequence homology. When the hydrophobic segments of the IL
      1R were aligned with similar segments of the GTPases, it became apparent that the
      IL-1Rs possess a number of conserved amino acids that represent plausible
      functional residues for base-specific binding of GTP, magnesium chelation, and
      phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues
      were found that is identical between ras and the IL-1R, and which is positioned
      to form part of the guanine base binding pocket. If this model is correct, then
      the IL-1Rs possess a highly conserved effector protein binding region, but one
      that is entirely unrelated to the effector regions of other superfamily members.
      Therefore, if the IL-1R is indeed a GTPase, then its activation function may be
      directed to as-yet unrecognized effector target proteins, as part of a unique
      cellular signal transduction pathway.

PMID- 8528084
TI  - A statistical mechanical model for hydrogen exchange in globular proteins.
AB  - We develop a statistical mechanical theory for the mechanism of hydrogen exchange
      in globular proteins. Using the HP lattice model, we explore how the solvent
      accessibilities of chain monomers vary as proteins fluctuate from their stable
      native conformations. The model explains why hydrogen exchange appears to involve
      two mechanisms under different conditions of protein stability: (1) a "global
      unfolding" mechanism by which all protons exchange at a similar rate, approaching
      that of the denatured protein, and (2) a "stable-state" mechanism by which
      protons exchange at rates that can differ by many orders of magnitude. There has
      been some controversy about the stable-state mechanism: does exchange take place
      inside the protein by solvent penetration, or outside the protein by the local
      unfolding of a subregion? The present model indicates that the stable-state
      mechanism of exchange occurs through an ensemble of conformations, some of which
      may bear very little resemblance to the native structure. Although most
      fluctuations are small-amplitude motions involving solvent penetration or local
      unfolding, other fluctuations (the conformational distant relatives) can involve
      much larger transient excursions to completely different chain folds.

PMID- 8528085
TI  - High-affinity binding of two molecules of cysteine proteinases to low-molecular
      weight kininogen.
AB  - Human low-molecular-weight kininogen (LK) was shown by fluorescence titration to
      bind two molecules of cathepsins L and S and papain with high affinity. By
      contrast, binding of a second molecule of cathepsin H was much weaker. The 2:1
      binding stoichiometry was confirmed by titration monitored by loss of enzyme
      activity and by sedimentation velocity experiments. The kinetics of binding of
      cathepsins L and S and papain showed the two proteinase binding sites to have
      association rate constants kass,1 = 10.7-24.5 x 10(6) M-1 s-1 and kass,2 = 0.83
      1.4 x 10(6) M-1 s-1. Comparison of these kinetic constants with previous data for
      intact LK and its separated domains indicate that the faster-binding site is also
      the tighter-binding site and is present on domain 3, whereas the slower-binding,
      lower-affinity site is on domain 2. These results also indicate that there is no
      appreciable steric hindrance for the binding of proteinases between the two
      binding sites or from the kininogen light chain.

PMID- 8528087
TI  - A ligand-induced conformational change in the Yersinia protein tyrosine
      phosphatase.
AB  - Protein tyrosine phosphatases (PTPases) play critical roles in the intracellular
      signal transduction pathways that regulate cell transformation, growth, and
      proliferation. The structures of several different PTPases have revealed a
      conserved active site architecture in which a phosphate-binding loop, together
      with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate
      and poise it for nucleophilic attack by an invariant cysteine nucleophile. We
      previously reported that binding of tungstate to the Yop51 PTPase from Yersinia
      induced a loop conformational change that moved aspartic acid 356 into the active
      site, where it can function as a general acid. This is consistent with the
      aspartic acid donating a proton to the tyrosyl leaving group during the initial
      hydrolysis step. In this report, using a similar structure of the inactive Cys
      403-->Ser mutant of the Yersinia PTPase complexed with sulfate, we detail the
      structural and functional details of this conformational change. In response to
      oxyanion binding, small perturbations occur in active site residues, especially
      Arg 409, and trigger the loop to close. Interestingly, the peptide bond following
      Asp 356 has flipped to ligate a buried, active site water molecule that also
      hydrogen bonds to the bound sulfate anion and two invariant glutamines. Loop
      closure also significantly decreases the solvent accessibility of the bound
      oxyanion and could effectively shield catalytic intermediates from phosphate
      acceptors other than water. We speculate that the intrinsic loop flexibility of
      different PTPases may be related to their catalytic rate and may play a role in
      the wide range of activities observed within this enzyme family.

PMID- 8528086
TI  - A preference-based free-energy parameterization of enzyme-inhibitor binding.
      Applications to HIV-1-protease inhibitor design.
AB  - The interface between protein receptor-ligand complexes has been studied with
      respect to their binary interatomic interactions. Crystal structure data have
      been used to catalogue surfaces buried by atoms from each member of a bound
      complex and determine a statistical preference for pairs of amino-acid atoms. A
      simple free energy model of the receptor-ligand system is constructed from these
      atom-atom preferences and used to assess the energetic importance of interfacial
      interactions. The free energy approximation of binding strength in this model has
      a reliability of about +/- 1.5 kcal/mol, despite limited knowledge of the unbound
      states. The main utility of such a scheme lies in the identification of important
      stabilizing atomic interactions across the receptor-ligand interface. Thus, apart
      from an overall hydrophobic attraction (Young L, Jernigan RL, Covell DG, 1994,
      Protein Sci 3:717-729), a rich variety of specific interactions is observed. An
      analysis of 10 HIV-1 protease inhibitor complexes is presented that reveals a
      common binding motif comprised of energetically important contacts with a rather
      limited set of atoms. Design improvements to existing HIV-1 protease inhibitors
      are explored based on a detailed analysis of this binding motif.

PMID- 8528088
TI  - Influence of divalent cations in protein crystallization.
AB  - We have tested the effect of several cations in attempts to crystallize the
      ligand-bound forms of the leucine/isoleucine/valine-binding protein (LIVBP) (M(r)
      = 36,700) and leucine-specific binding protein (LBP) (M(r) = 37,000), which act
      as initial periplasmic receptors for the high-affinity osmotic-shock-sensitive
      active transport system in bacterial cells. Success was achieved with Cd2+
      promoting the most dramatic improvement in crystal size, morphology, and
      diffraction quality. This comes about 15 years after the ligand-free proteins
      were crystallized. Nine other different divalent cations were tried as additives
      in the crystallization of LIVBP with polyethylene glycol 8000 as precipitant, and
      each showed different effects on the crystal quality and morphology. Cd2+
      produced large hexagonal prism crystals of LIVBP, whereas a majority of the
      cations resulted in less desirable needle-shaped crystals. Zn2+ gave crystals
      that are long rods with hexagonal cross sections, a shape intermediate between
      the hexagonal prism and needle forms. The concentration of Cd2+ is critical. The
      best crystals of the LIVBP were obtained in the presence of 1 mM CdCl2, whereas
      those of LBP, with trigonal prism morphology, were obtained at a much higher
      concentration of 100 mM. Both crystals diffract to at least 1.7 A resolution
      using a conventional X-ray source.

PMID- 8528089
TI  - The coming of age of mass spectrometry in peptide and protein chemistry.

PMID- 8528090
TI  - SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins.
AB  - Single copies of an approximately 65-70 residue domain are shown to be present in
      the sequences of 14 eukaryotic proteins, including yeast byr2, STE11, ste4, and
      STE50, which are essential participants in sexual differentiation. This domain,
      named SAM (sterile alpha motif), appears to participate in other developmental
      processes because it is also present in Drosophila polyhomeotic gene product and
      related homologues, which are thought to regulate determination of segmental
      specification in early embryogenesis. Its appearance in byr2 and STE11, which are
      MEK kinases, and in proteins containing pleckstrain homology, src homology 3, and
      discs-large homologous region domains, suggests possible participation in signal
      transduction pathways.

PMID- 8528091
TI  - Crystallization and preliminary X-ray crystallographic analysis of arylesterase
      from Vibrio mimicus.
AB  - Single crystals of arylesterase (EC 3.1.1.2) from Vibrio mimicus have been
      obtained from ammonium sulfate as a precipitant at room temperature for 2 months.
      The present crystals diffract up to 2.2 A resolution and belong to monoclinic
      space group P2(1). The cell dimensions are a = 55.65(1) A, b = 53.46(1) A, c =
      65.79(1) A, and beta = 106.54(1) degrees. There are two molecules of molecular
      weight 22 kDa in an asymmetric unit with a solvent content of 43%.

PMID- 8528092
TI  - A calorimetric characterization of the salt dependence of the stability of the
      GCN4 leucine zipper.
AB  - The effects of different salts (LiCl, NaCl, ChoCl, KF, KCl, and KBr) on the
      structural stability of a 33-residue peptide corresponding to the leucine zipper
      region of GCN4 have been studied by high-sensitivity differential scanning
      calorimetry. These experiments have allowed an estimation of the salt dependence
      of the thermodynamic parameters that define the stability of the coiled coil.
      Independent of the nature of the salt, a destabilization of the coiled coil is
      always observed upon increasing salt concentration up to a maximum of
      approximately 0.5 M, depending on the specific cation or anion. At higher salt
      concentrations, this effect is reversed and a stabilization of the leucine zipper
      is observed. The effect of salt concentration is primarily entropic, judging from
      the lack of a significant salt dependence of the transition enthalpy. The salt
      dependence of the stability of the peptide is complex, suggesting the presence of
      specific salt effects at high salt concentrations in addition to the nonspecific
      electrostatic effects that are prevalent at lower salt concentrations. The data
      is consistent with the existence of specific interactions between anions and
      peptide with an affinity that follows a reverse size order (F- > Cl- > Br-).
      Under all conditions studied, the coiled coil undergoes reversible thermal
      unfolding that can be well represented by a reaction of the form N2<==>2U,
      indicating that the unfolding is a two-state process in which the helices are
      only stable when they are in the coiled coil conformation.

PMID- 8528093
TI  - The golden years of Protein Science. Banquet address at the First European
      Symposium of the Protein Society, Davos, Switzerland, May 30, 1995.

PMID- 8528094
TI  - The contribution of marker gene studies to hemopoietic stem cell therapies.
AB  - Although the transfer of "therapeutic" genes into hemopoietic stem cells (HSC)
      offers many opportunities to treat a wide range of human disease, the low
      efficiency of transfer and limited expression of the transferred gene have so far
      largely prevented any direct beneficial effect from being obtained. However, gene
      marker studies in which the transferred genes are used simply to track the
      individual components of the infused HSC have already shown their utility.
      Genetic marking may be used to identify cells capable of causing relapse after
      autologous bone marrow transplantation and to distinguish cells in the graft
      capable of preventing malignant disease. Marking may also be used to analyze the
      consequences of ex vivo or in vivo manipulations of the HSC which are intended to
      accelerate engraftment or augment gene transfer efficiencies. Information
      obtained from these studies should therefore not only improve the outcome of HSC
      based therapies, but also aid in the introduction of successful gene therapy
      protocols.

PMID- 8528095
TI  - Preclinical biology of interleukin 11: a multifunctional hematopoietic cytokine
      with potent thrombopoietic activity.
AB  - Interleukin 11 (IL-11) is a multifunctional hematopoietic cytokine which was
      originally identified as a factor produced by an IL-1-stimulated primate stromal
      cell line. The in vitro biological activities of recombinant human (rHu)IL-11
      result predominantly from synergistic interactions with other growth factors. In
      combination with other cytokines, rHuIL-11 has been shown to support the
      formation of primitive hematopoietic and lymphohematopoietic progenitor colonies
      from bone marrow, to promote erythroid burst formation and to stimulate both
      early and late stages of megakaryocyte proliferation and differentiation. rHuIL
      11 is biologically active in mice, rats, dogs and primates when administered as a
      single agent in vivo. The predominant effect of rHuIL-11 in naive mice was on
      cells of the megakaryocytic lineage, increasing the number of bone marrow
      megakaryocyte progenitors, stimulating megakaryocyte endoreplication and
      increasing peripheral platelet counts in a dose-dependent fashion. Similar
      megakaryocytic stimulatory activity was seen in nonhuman primates treated with
      rHuIL-11 where platelet counts were increased by as much as 300%. In several
      models of severe myelosuppression induced by chemotherapy and/or irradiation and
      in bone marrow transplant models, there were multilineage hematopoietic
      stimulation following rHuIL-11 treatment. In these models, accelerated recovery
      of platelets was a consistent observation, while some models show enhanced
      neutrophil and red blood cell recovery as well. These results from preclinical
      studies confirm the broad spectrum of biological activities exhibited by rHuIL-11
      in vitro, and suggest that this cytokine may be an effective agent in the
      treatment of myelosuppression and thrombocytopenia associated with cancer
      chemotherapy and bone marrow transplantation.

PMID- 8528096
TI  - Perspective of rhGM-CSF in the treatment of neutropenic infections and aggressive
      lymphomas.
AB  - Non-Hodgkin lymphomas (NHL) of intermediate and high-grade malignancy respond
      well to doxorubicin-containing regimens, but long-term survival does not exceed
      30% in large studies with long-term follow-up. Any attempt to improve this
      somehow disappointing result by adding more drugs, increasing doses or shortening
      time intervals of chemotherapy have so far failed in randomized settings. Even
      autologous bone marrow transplantation (ABMT) could not improve long-term
      survival when applied in first remission of the disease. Prophylactic use of
      hematopoietic growth factors in the chemotherapy of aggressive NHL did prevent
      neutropenia and positively influenced the occurrence of infectious complications,
      and also led to an increase of dose intensity (DI) by 15% but this did not affect
      survival. In contrast, a retrospective analysis of an NHL study showed that a
      high DI may in fact be deleterious rather than beneficial. Thus the prophylactic
      use of hematopoietic growth factors still has to be considered experimental in
      the chemotherapy of NHL and should be studied in controlled settings like the one
      proposed here.

PMID- 8528097
TI  - The stromal cells' guide to the stem cell universe.
AB  - Pluripotent hematopoietic stem cells have emerged as a heterogeneous population
      of cells that differ in phenotype and repopulation kinetics. Stem cells in vitro
      and in vivo are dependent upon stromal cells for their proliferation and
      differentiation. Thus, stromal cells can be viewed as tools to analyze the
      physiological conditions that regulate stem cells. Stromal cell lines that
      support stem cells are infrequent, which supports the interpretation that stromal
      cells create distinct niches that regulate stem cell development. A model of stem
      cell maintenance is presented that predicts that stromal cell-bound molecules
      protect stem cells from differentiation. The stroma compartment is highly
      adaptable and can change its function in response to external stimuli. Thus, it
      is tempting to speculate that the stroma acts as a translator of peripheral
      signals for stem cells.

PMID- 8528098
TI  - Relationships between B cell cytokine production in secondary lymphoid follicles
      and apoptosis of germinal center B lymphocytes.
AB  - In vivo or in vitro activated human B lymphocytes can produce a wide spectrum of
      cytokines which are involved in the regulation of hematopoiesis and of the
      inflammatory and immune responses. Three major B cell subsets have been
      identified in peripheral lymphoid organs: the germinal center (GC), the mantle
      zone (MZ) and the marginal zone B lymphocytes. GC and MZ B cells can be isolated
      as CD39- surface (s)IgD- or CD39+ sIgD+ cells, respectively. Therefore, it is now
      possible to investigate the cytokine producing potential of purified GC and MZ B
      lymphocytes. In this article, the optimal conditions for the assessment of
      cytokine production by human B cells are first discussed; thereafter, the
      spectrum of B lymphocyte-derived cytokines is described together with their
      possible physiological meaning. Next, data concerning the cytokines released in
      vitro by either GC or MZ B cells are presented. Some cytokines, such as
      granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM
      CSF), are produced only by GC or MZ B lymphocytes, respectively, whereas other
      cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6)
      or IL-10 are synthesized by both B cell subsets. Finally, the relationships
      between B cell-derived cytokines and apoptosis of GC B lymphocytes are discussed,
      and a hypothetical model of the cytokine networks in secondary lymphoid follicles
      is presented. It is expected that these notions will help to clarify the
      pathophysiology of lymphoproliferative and autoimmune diseases.

PMID- 8528099
TI  - Prodrugs in cancer chemotherapy.
AB  - At present, chemotherapy is not very effective against common solid cancers,
      especially once they have metastasized. However, laboratory experiments and
      studies on dose intensification in humans have indicated that some anticancer
      agents might be curative, but only if the dose given was very much higher than
      that attainable clinically. Prodrugs activated by enzymes expressed at a high
      level in tumors can deliver at least 50-fold the normal dose and can cure animals
      with tumors normally resistant to chemotherapy. The approach is not practicable
      clinically because of the rarity of human tumors expressing a high level of an
      activating enzyme. However, new therapies have been proposed that overcome this
      limitation of prodrug therapy. Enzymes that activate prodrugs can be directed to
      human tumor xenografts by conjugating them to tumor-associated antibodies. After
      allowing for the conjugate to clear from the blood a prodrug is administered
      which is normally inert, but which is activated by the enzyme delivered to the
      tumor. This procedure is referred to as ADEPT (antibody-directed enzyme prodrug
      therapy). Using different combinations of antibody, enzyme and prodrug, many
      classes of human tumor xenograft have been shown to be very sensitive to this
      procedure although in most cases they are quite resistant to conventional
      chemotherapy. Early clinical trials are promising and indicate that ADEPT may
      become an effective treatment for all solid cancers for which tumor-associated or
      tumor-specific antibodies are known. Tumors have also been targeted with the
      genes encoding for prodrug activating enzymes. This approach has been called
      virus-directed enzyme prodrug therapy (VDEPT) or more generally GDEPT (gene
      directed enzyme prodrug therapy) and has shown good results in laboratory
      systems. These new therapies may finally realize the potential of prodrugs in
      cancer chemotherapy.

PMID- 8528100
TI  - Broad inter-individual variations in circulating progenitor cell numbers induced
      by granulocyte colony-stimulating factor therapy.
AB  - The elevated white cell counts (WCC) and myeloid progenitor cell levels in the
      blood induced by granulocyte colony-stimulating factor (G-CSF) treatment were
      studied in three settings: cancer patients previously treated with
      chemo/radiotherapy (n = 13), untreated cancer patients (n = 5) and normal
      volunteers (n = 9). The inter-individual variations in progenitor cell
      mobilization responses to G-CSF and the impact of previous chemo/radiotherapy
      were investigated. The absolute levels of circulating progenitor cells, but not
      total white cells, were reduced significantly in the pretreated cancer patients
      (median 961, range 289-3355 per ml blood) as compared to untreated cancer
      patients (median 9891, range 2219-16625 per ml blood). In each setting, wide
      ranges of circulating progenitor cell numbers were observed, and the variation in
      progenitor cell numbers was considerably greater than observed for the WCC.
      However, progenitor cell numbers in normal volunteers (942-25296 per ml blood)
      demonstrated as much variance as observed in pretreated cancer patients. This
      broad physiological variation in progenitor cell levels induced by G-CSF needs to
      be considered when designing strategies for allogeneic peripheral blood stem cell
      transplantation.

PMID- 8528101
TI  - Hematopoietic stem cells found in lineage-positive subsets in the bone marrow of
      5-fluorouracil-treated mice.
AB  - It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers
      radioprotection. To investigate this effect, we performed bone marrow
      transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days
      prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow
      (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the
      number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was
      markedly decreased relative to those from untreated controls. These results
      showed that the surface characteristics of cells that contributed to this radio
      protective effect differ from those of stem cells as reported recently. BM MNC of
      mice treated with 5-FU were separated on the basis of expression of the lineage
      specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally
      irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective
      effects such that 100% and 60% survived, respectively. Flow cytometric analysis
      165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice
      transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice,
      respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which
      showed radioprotective effects on a secondary irradiated host were detected from
      mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these
      findings demonstrated that stem cells expressing Lin+ present in the BM of mice
      treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an
      important role in the recovery of myeloablative mice.

PMID- 8528102
TI  - Comparison of purity and enrichment of CD34+ cells from bone marrow, umbilical
      cord and peripheral blood (primed for apheresis) using five separation systems.
AB  - Interest in the isolation and characterization of primitive hemopoietic cells in
      both the clinical and research fields has rapidly increased. In parallel,
      different purification systems have been developed to isolate these cells. We
      have compared five different methods for separation of CD34+ cells from human
      umbilical cord blood, normal bone marrow and apheresis harvests and analyzed
      purity, recovery, yield and enrichment of colony forming cells (CFC) for each
      individual system. Our results indicate that the most reliable methods of
      purification for all samples were fluorescence activated cell sorting (FACS) and
      magnetic activated cell sorting (MACS) which consistently yielded high purities
      (> 70%) and enrichment of CFC. In this respect the enrichment of CFC from the
      MACS was superior to all the other systems including FACS. Similar results (>
      70%) for purity were obtained using avidin affinity columns and a biotinylated
      antibody but neither yield nor CFC enrichment approached the values achieved with
      MACS. On average CFC enrichment using these affinity columns was greater than
      that observed for FACS while the purity was comparable. Both CELLector flasks and
      immunomagnetic beads coated with CD34 antibodies were less effective in our hands
      in separating purified populations of progenitor cells. Both purity and CFC
      enrichment of CD34+ cells using these methods were at least 50% lower than
      obtained with either FACS, MACS or affinity columns.

PMID- 8528103
TI  - Density separation of umbilical cord blood and recovery of hemopoietic progenitor
      cells: implications for cord blood banking.
AB  - Umbilical cord blood (CB) has been evaluated as a potential source of
      hematopoietic stem cells suitable for clinical use in the transplantation
      setting. Previous reports have documented a significant loss of progenitor cells
      by any manipulation other than cryopreservation. We have evaluated the
      feasibility of fractionating and cryopreserving CB samples with minimal loss of
      progenitor cells. We have compared various separation procedures based on
      different density gradients in the attempt to obtain the highest depletion of red
      blood cells (RBC) while maintaining the highest recovery of progenitor cells. We
      compared three different densities of Percoll (1.069 g/ml, 1.077 g/ml, 1.084
      g/ml), sedimentation over poligeline (Emagel ) and sedimentation over poligeline
      followed by separation over Ficoll/Hypaque (F/H). Separated samples (n = 25) were
      analyzed for recovery of CD34+ cells and progenitor cells (CFU-GEMM, BFU-E, CFU
      GM). Separation by sedimentation over poligeline followed by F/H allowed the
      highest depletion of RBC (hematocrit of the final cellular suspension 0.4 +/-
      0.1%) while maintaining high recovery of CD34+ cells (85.3 +/- 5.6%) and total
      recovery for CFU-GEMM, BFU-E and CFU-GM. After cryopreservation, recovery of
      clonogenic progenitors was 82% for CFU-GEMM, 94% for BFU-E, 82% for CFU-GM and
      90% for colony-forming units (CFUs) after five weeks of long-term culture (LTC).
      We further evaluated the effect of stem cell factor (SCF) on the in vitro growth
      of hemopoietic progenitors and on replating efficiency.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8528104
TI  - Directed endothelial differentiation of cultured embryonic yolk sac cells in vivo
      provides a novel cell-based system for gene therapy.
AB  - Cultured murine yolk sac cells transfected with the cytomegalovirus immediate
      early promoter/human growth hormone (CMVIE-hGH) fusion gene, expressing high
      levels of hGH in culture, and suspended in Matrigel were subcutaneously (s.c.)
      injected into experimental mice. The injected cells were shown to form discrete
      vesicular structures within the Matrigel implant, suggesting directed
      differentiation of the embryonic yolk sac cells into endothelial tissue. Human
      growth hormone radioimmune assay of these mice showed sustained physiologically
      significant levels of hGH in their serum for beyond four months. These results
      confirmed that long-term cultured murine embryonic yolk sac cells can be induced
      to differentiate into endothelial cells both in vivo and in vitro and suggested a
      novel approach to the delivery to the circulation of therapeutic proteins for the
      treatment of inherited and acquired diseases.

PMID- 8528105
TI  - Quantitative and qualitative comparative analysis of gradient-separated
      hematopoietic cells from cord blood and chemotherapy-mobilized peripheral blood.
AB  - Some of the uncertainty regarding the use of cord blood (CB) in transplant
      settings includes the suspected relative rarity of hematopoietic stem cells (SC)
      in CB and the feasibility of incorporating a cell separation protocol to remove
      red blood cells, which may result in an unacceptable loss of SC. To address this
      uncertainty, we isolated a SC fraction by Percoll or Ficoll gradients from CB and
      peripheral blood (PB), which had been mobilized by chemotherapy. The frequencies
      of mononuclear cells (MNC), CD34+ cells, colony-forming units granulocyte
      macrophage (CFU-GM), and the output of colony-forming cells (CFC) after five
      weeks in long-term culture (LTC) assay were then evaluated. The mean numbers of
      these cells per ml of CB sample before gradient separation were, respectively,
      4.9 x 10(6), 13.8 x 10(4), 3.0 x 10(3) and 681 (n = 37). In the recovery phase of
      PB, these numbers were, respectively, 2.0 x 10(6), 14.9 x 10(4), 3.5 x 10(3) and
      270 per ml of processed blood at apheresis (n = 35). After Percoll separation,
      the recovery rates of these cells were, respectively, 29%, 92%, 97% and 95% in
      CB, and 65%, 87%, 123% and 102% in PB. After Ficoll separation of CB, the rates
      were, respectively, 55%, 107%, 92% and 105%. These results suggest that CB
      contains an adequate number of more immature progenitors which can be retained
      after cell separation with Percoll or Ficoll, thereby making it feasible to
      incorporate a cell processing procedure into a CB transplant protocol. Percoll
      separation provided a greater enrichment of cells than Ficoll.

PMID- 8528107
TI  - In memoriam Professor Laszlo G. Lajtha 1920-1995.

PMID- 8528106
TI  - Analysis of mutations of neurofibromatosis type 1 gene and N-ras gene in acute
      myelogenous leukemia.
AB  - Neurofibromatosis type 1 (NF1) gene is a tumor suppressor gene, and the NF1 gene
      product, neurofibromin, can downregulate the N-ras gene. Because the N-ras gene
      is often mutated in acute myelogenous leukemia (AML), we wondered if the NF1 gene
      might be mutated in those AML samples not having N-ras mutations. We investigated
      the mutational status of the N-ras gene and the FLR exon of codons 1371-1423 of
      the open reading frame of the full-length NF1 cDNA, which has a strong homology
      with the mammalian ras GTPase-activating protein (GAP), especially for a stretch
      of three consecutive amino acids (F, L, R), by single-strand conformation
      polymorphism analysis and direct sequencing in samples from patients with AML. Of
      48 AML patients, 10 (21%) had point (missense) mutations of the N-ras gene
      involving codons 12, 13 and 61. However, mutations in the FLR exon of the NF1
      gene were not detected in any of the AML samples. We also examined the difference
      of clinical response to induction therapy between AML patients with and without N
      ras mutation. A significantly lower rate of complete remission was noted in
      individuals with N-ras gene mutations. These results suggest that mutation of the
      NF1 gene, at least in the FLR exon, is very rare in AML and the NF1 gene probably
      is not a functional complement of the N-ras gene mutation. The presence of N-ras
      gene mutation may be associated with a lower clinical response to antileukemic
      therapy.

PMID- 8528108
TI  - Tissue impedance: a historical overview.
AB  - Over the past 150 years the study of the electrical properties of various
      biological tissues has been undertaken by researchers from a wide variety of
      scientific backgrounds. This has, unfortunately, led to the existing range of
      confusing and misunderstood terminology/concepts. Some of the most important are
      presented and explained.

PMID- 8528109
TI  - Incorporating a priori information into the Sheffield filtered backprojection
      algorithm.
AB  - The Sheffield image reconstruction algorithm is based on the assumption that the
      initial conductivity distribution of the body being imaged is uniform. In many
      situations this assumption is violated. Previous attempts at incorporating a
      priori information by modifications to the backprojection matrices were
      ineffective. An alternative method of including a priori information became
      apparent following the recent reformulation of the Sheffield image reconstruction
      algorithm. Applying matrix algebra to the image reconstruction equations reveals
      that the incorporation of a priori information can be considered as either a
      modification to the original backprojection matrix or a component of a composite
      data filter. A simple two-dimensional model of the adult head was chosen to test
      this approach. The results of imaging studies using synthetic data derived from
      this model show that a priori information has been successfully incorporated into
      the image reconstruction process. The ability to include a priori information
      into the image reconstruction process may have significant implications for the
      more challenging applications of EIT such as imaging the adult head.

PMID- 8528110
TI  - 3D reconstruction in electrical impedance imaging using a direct sensitivity
      matrix approach.
AB  - This paper represents a reconstruction algorithm using a direct sensitivity
      matrix (DSM) approach for fast 3D image reconstruction in electrical impedance
      imaging. The boundary element method (BEM) is used in the construction of this
      matrix. The first images of a conductivity perturbation inside a sphere are
      reconstructed, using theoretical data.

PMID- 8528111
TI  - Data processing techniques for serial EIT spectroscopy images: a review of some
      preliminary results.
AB  - Mutlifrequency EIT imaging should allow specific organs within the body to be
      identified by their impedance spectrum, and the use of parametric imaging should
      lead to a much greater freedom from movement artefacts. This will make EIT more
      attractive as a monitoring technique, but the data rate will require automated
      processing of the images. The application of dynamic regions of interest,
      generated on a frame by frame basis, is described, with examples from the imaging
      of neonatal lungs and adult stomach. The lung can be objectively identified on a
      single frame from the fRSC, SC and RC images, but the stomach could only be
      identified on the dynamic images.

PMID- 8528112
TI  - Detecting oesophageal-related changes using electrical impedance tomography.
AB  - Preliminary work has been carried out using the Sheffield mark II real time EIT
      system, looking for changes in conductivity which occur in the stomach and
      oesophagus following a swallow of a small volume of either a conducting or a non
      conducting liquid. This has been done using three different configurations: a
      conventional transverse array placed around the thorax, a rosette array on the
      abdomen, and a rosette array placed on the back. Results show a significant
      difference between the two liquids, which can be detected equally well by the
      three electrode configurations.

PMID- 8528113
TI  - In vitro tissue characterization and modelling using electrical impedance
      measurements in the 100 Hz-10 MHz frequency range.
AB  - In vitro electrical impedance spectrometry was performed on tissue samples
      excised from sheep. Measured data have been processed to reduce dispersion in
      measurements and to provide criteria useful for tissue comparison. Two electrical
      models are proposed for tissues exhibiting a one-circle impedance locus and a two
      circle impedance locus. Measurement results and electrical parameters of tissues
      and models fitted to experimental data are presented. Model sensitivity to
      parameter variations is discussed.

PMID- 8528114
TI  - Problems involved in temperature measurements using EIT.
AB  - In cancer therapy, hyperthermic treatment by microwaves requires a non-invasive
      and reliable method for measuring the temperature distribution inside the body.
      EIT seems to be able to evaluate the temperature-dependent tissue impedance for
      delivering the temperature profile in a cross-section of the body. Assuming a
      temperature coefficient of the resistivity of an electrolyte of about -2% degrees
      C-1 and temperature measurement to an accuracy of 0.5 degree C, the error in
      impedance measurement must be lower than 1%. Irrespective of the accuracy of the
      tomographic measuring system itself, a problem arises from the fact that the
      fluid content in the tissue as well as the fluid distribution between the
      extracellular and the intracellular compartment change with temperature.
      Measurements of the impedance spectra of skeletal muscle and tumours of rats
      during hyperthermic treatment deliver very different temperature coefficients of
      the resistivity from -1.3% degree C-1 to -3% degree C-1, thus questioning the
      feasibility of the EIT as a temperature measuring method. However, changes in the
      tissue caused by hyperthermia (e.g., fluid shifts, development of oedema and
      membrane disintegration) can be detected.

PMID- 8528115
TI  - Changes in the thoracic impedance distribution under different ventilatory
      conditions.
AB  - The present study was performed with the aim of checking the suitability of EIT
      in imaging regional thoracic impedance variations during lung ventilation under
      predefined conditions and to compare EIT with established reference techniques. A
      new technique of functional EIT imaging designed to visualize physiologically
      relevant information from the sequentially registered series of thoracic
      distributions was introduced. Experiments were performed on five spontaneously
      breathing healthy subjects and on 12 anaesthetized supine pigs. 16 electrodes
      were placed around the thorax and consecutive transthoracic impedance
      distributions were measured at a rate of 1 Hz (Sheffield APT system mark I,
      IBEES, Sheffield, UK). Several voluntary breathing manoeuvres were performed in
      human subjects and the tracings of local impedance were compared with standard
      spirometry. In animal experiments EIT was applied during artificial ventilation
      at different ventilation rates and during stepwise passive emptying and filling
      of either one or both lungs while the respiratory muscles were relaxes. Further,
      selective blockade of lung regions resulting in regionally reduced ventilation
      was performed and the capability of EIT to follow and differentiate local
      ventilatory disturbances was checked by reference techniques (x-ray and staining
      methods). The experiments revealed an overall agreement between the spirometric
      and impedance data in all breathing patterns performed. A linear relationship
      between changes of the air content of the lungs and the regional thoracic
      impedance was shown (intraindividual correlation coefficient range, 0.986-0.999;
      n = 12 animals). The functional images of the impedance distribution across the
      thorax reproduced adequately the typical anatomical characteristics of the pig
      and the human thorax. The spatial resolution of EIT functional images was
      sufficient to differentiate lung areas corresponding to approximately 20 ml
      tissue volume. EIT with the additional evaluation procedure of functional imaging
      was shown to be a suitable and reliable method of imaging different ventilatory
      conditions with the potential to become a useful tool for monitoring respiratory
      function.

PMID- 8528116
TI  - Multifrequency and parametric EIT images of neonatal lungs.
AB  - The aims of the study were to investigate the problems involved in making
      multifrequency EIT measurements on neonates and to compare the images obtained
      with the results from a group of normal adults. The Sheffield electrical
      impedance tomographic spectroscopy (EITS) system acquires multifrequency data
      using a set of eight drive and eight receive electrodes. EITS measurements were
      made on an inhomogeneous group of 10 neonates admitted to the special care baby
      unit for observation and feeding. R/S, characteristic frequency, RC and SC
      parameters were generated using the Cole equation. Comparisons of the parameters
      were made with data collected from normal adults in another study. We have shown
      that it is possible to obtain EITS parametric images of neonatal lungs and that
      there are some differences in Cole parameters between the adult and neonatal
      groups.

PMID- 8528117
TI  - Application of electrical impedance tomography in diagnosis of emphysema--a
      clinical study.
AB  - In this paper, electrical impedance tomography (EIT) ventilation images from a
      group of 12 patients (11 patients with emphysema and one patient with only
      chronic obstructive pulmonary disease (COPD) (chronic bronchitis) and a group of
      15 normal subjects were acquired using a Sheffield mark 1 EIT system, at the
      levels of second, fourth and sixth intercostal spaces. Patients were diagnosed
      based on CT scans of the thorax, pulmonary function tests and posteroanterior x
      ray graphs. One of the patients with emphysema has also a malignant lung tumour.
      Ventilation-related conductivity changes at total lung capacity (TLC) relative to
      residual volume were measured quantitatively in EIT images. These quantitative
      values demonstrate marked differences compared to those values obtained from the
      EIT images of 15 normal subjects. The EIT images of the patients were also
      compared with the CT images. In addition to the visual examination of the EIT
      images a statistical confidence test is applied to compare the images of the
      patients with the images of the normal subjects. Prior to statistical analysis
      all images are normalized with TLC to minimize the effect of mismatch between the
      TLC of different subjects. A normal mean image is created by averaging the
      normalized images from the normal subjects, at each intercostal space level. Than
      a 95% confidence interval is defined for each normal mean image. For each image
      of the patients, a confidence test image, which represents the deviations from
      the 95% confidence interval of the normal mean image, is created. The regions
      with emphysematous bulla and parencyhma are detectable in the confidence test
      images as regions of positive and negative deviations from the confidence
      interval of the normal mean, respectively. In the test images, it is possible to
      differentiate emphysematous parenchyma from emphysematous bulla, tumour
      structure, and COPD. However, the emphysematous bulla, the tumour structure, and
      COPD result in the same type of defect in the test images and are therefore
      indistinguishable from each other. In some case, off-plane contributions in the
      EIT images may result in underestimation of the defects. EIT may be a useful
      screening device in detecting emphysema rather than a diagnostic tool.

PMID- 8528118
TI  - Singularities of mixed boundary value problems in electrical impedance
      tomography.
AB  - The importance of accurate mathematical modelling in the development of image
      reconstruction algorithms for electrical impedance tomography (EIT) has been
      discussed in a number of recent papers. It is particularly important in iterative
      reconstruction schemes where the forward problem of calculating the electric
      potential from Neumann boundary data is solved many times. One area which needs
      to be considered it the mathematical modelling of the electrodes used in the
      technique. In this paper we discuss one of the more sophisticated models which
      has been proposed and present the results of a number of numerical and analytic
      calculations which we have made as a contribution to the understanding of this
      question.

PMID- 8528119
TI  - The grouped node technique as a means of handling large electrode surfaces in
      electrical impedance tomography.
AB  - A finite-element method employing a grouped node technique as a means of handling
      large electrode surfaces in electrical impedance process tomography is presented.
      The technique groups sets of nodes representing discrete boundary electrodes in a
      two-dimensional finite-element mesh into corresponding sets of single nodes via a
      transformation matrix G. The subsequent field solution is obtained based on the
      new boundary conditions in the standard way after implementing this procedure.
      Comparison of the resultant boundary voltage profiles from this approach against
      measurements made on laboratory scale phantoms are reported.

PMID- 8528120
TI  - A method for comparative evaluation of EIT algorithms using a standard data set.
AB  - The point spread function (PSF) is the most widely used tool for quantifying the
      spatial resolution of imaging systems. However, prerequisites for the proper use
      of this tool are linearity and space invariance. Because EIT is non-linear it is
      only possible to compare different reconstruction algorithms using a standard
      data set. In this study, the FEM is used to generate simulation data, which are
      used to investigate the non-linear behaviour of EIT, the space dependence of its
      PSF and its capability of resolving nearby objects. It is found that for the case
      of iterative backprojection (IterB), the full width half maximum (FWHM) values of
      single-object perturbations for central, intermediate and peripheral high
      contrast objects are 27%, 18% and 14% of the imaging region diameter
      respectively. For the method based on singular value decomposition of the
      Geselowitz lead sensitivity matrix (GS-SVD), the FWHM is not space dependent and
      is 12% of the imaging region diameter. Conclusions obtained using single-object
      PSF studies must also be checked with double-object or more complex perturbations
      because EIT is non-linear. For example, the GS-SVD method fails to detect two
      widely separated objects unless the truncation level of SVD is carefully
      adjusted. With more truncation, however, the resolution of the method is
      worsened. Based on these and similar observations a set of simulation data, which
      is proposed for comparative evaluation of different EIT algorithms, is specified
      and explained in the conclusion section.

PMID- 8528121
TI  - Experimental validation of a novel reconstruction algorithm for electrical
      impedance tomography based on backprojection of Lagrange multipliers.
AB  - A novel approach to image reconstruction for electrical impedance tomography
      (EIT) has been developed. It is based on a constrained optimization technique for
      the reconstruction of difference resistivity images without finite-element
      modelling. It solves the inverse problem by optimizing a cost function under
      constraints, in the form of normalized boundary potentials. Its application to
      the neighboring data collection method is presented here. Mathematical models are
      developed according to specified criteria. These express the reconstructed image
      in terms of one-dimensional Lagrange multiplier functions. The reconstruction
      problem becomes one of estimating these functions from normalized boundary
      potentials. This model is based on a cost criterion of the minimization of the
      variance between the reconstructed and the true resistivity distributions. The
      algorithm was tested on data collected in a cylindrical saline-filled tank. A
      polyacrylamide rod was placed in various positions with or without a peripheral
      plaster of Paris ring in place. This was intended to resemble the conditions
      during EIT of epileptic seizures recorded with scalp or cortical electrodes in
      the human head. One advantage of this approach is that compensation for non
      uniform initial conditions may be made, as this is a significant problem in
      imaging cerebral activity through the skull.

PMID- 8528122
TI  - Conducting boundary strategy: a new technique for medical EIT.
AB  - A medical application of a new measurement strategy developed for process
      tomography is presented. By exchanging the current streamlines with the
      equipotential lines impedance tomography can be performed using unipolar
      measurements. The equipotential lines are now parallel to the conducting boundary
      and voltage measurement is made between this boundary and an insulated electrode.
      A set of 32 electrodes was placed around the chest with every alternate electrode
      connected to form the 'conducting boundary'. A total of 120 independent
      measurements were available. Reciprocity error without common mode feedback was
      0.5% with a dynamic range of only 1:1.12. The images were comparable to that
      reconstructed using adjacent drive strategy.

PMID- 8528123
TI  - Impedance imaging using induced currents.
AB  - The principal features of an electrical impedance tomography system using induced
      currents are described. Images of the distribution of conductivity in a two
      dimensional phantom are obtained using an algorithm based on a sensitivity
      matrix. Results are also presented which demonstrate the separation of
      conductivity and permittivity images from measurements of the complex peripheral
      voltage, the formation of unreferenced permittivity images, and the use of
      capacitively coupled electrodes in a measuring system without direct electrical
      contact.

PMID- 8528124
TI  - A Cole phantom for EIT.
AB  - A phantom was designed for testing and comparing multifrequency EIT data
      collection systems. The phantom simulates a cylinder of homogeneous conductor
      with 16 drive and 16 receive electrodes interleaved. Combinations of resistors
      and capacitors were used to simulate the complex impedance, Z*, of a typical
      tissue in the frequency range 8-2048 kHz obeying the Cole equation Z* = Z
      infinity + (Z0 - Z infinity)/[1 + (if/fc)(1- alpha )] where Z* is the complex
      impedance at frequency f, Z0 and Z infinity are the limiting values of impedance
      at low and high frequencies, fc is the characteristic frequency and alpha is a
      constant. A practical phantom was then constructed on which four different sets
      of spectroscopic parameters could be selected: (i) alpha = 0.20, fc = 150 kHz,
      Z0/Z infinity = 3.31; (ii) alpha = 0, fc = 273 kHz, Z0/Z infinity = 2.64; (iii)
      alpha = 0, fc = 71.1 kHz, Z0/Z infinity = 1.36; and (iv) Z0/Z infinity = 1.00
      with no dispersion.

PMID- 8528125
TI  - A fast parametric modelling algorithm with the Powell method.
AB  - This paper presents a model that comprises only two parameters (R/S, fr) and the
      application of three function minimization algorithms (simplex, Powell and
      modified Powell) to this model to obtain parametric images. Comparisons among the
      three algorithms in terms of efficiency and reliability were carried out. It was
      found that, with proper initialization by taking the shape of the modelled data
      into consideration, the minimization function can be approximated by a quadratic
      function near the minimum point, therefore the iteration times can be minimized
      in the modified Powell method. The results show that with the modified Powell
      method a substantial reduction of computation time can be achieved in the
      parametric imaging. This makes it possible to obtain a 16 x 16 parametric image
      in 1 s.

PMID- 8528126
TI  - Tissue impedance spectra and the appropriate frequencies for EIT.
AB  - The complex impedance of each kind of tissue depends on the frequency in a
      characteristic manner. Using appropriate measuring frequencies, EIT can provide a
      differentiating insight into the interior of a body. Therefore, a knowledge of
      the tissue impedance spectra of various organs is essential for choosing the
      appropriate frequencies. The impedance data of various tissues in different
      states (normal, altered by ischaemia or cancerous) show that the characterizing
      differences occur at frequencies below 500 kHz and down to a few kilohertz.
      Moreover, the spectra show that the imaginary component of impedance essentially
      contributes to the characterization of the kind and state of a tissue, even
      though the dissipative and reactive components are connected by the Kramers
      Kronig relations. The course of a dispersion and the position in the frequency
      range, determined by the distribution of the time constants in the tissue, are
      clearly presented by the imaginary component. Tomographic imaging combined with
      spectroscopy for tissue characterization requires a frequency range of at least
      10-800 kHz. The upper frequency limit depends on the fluid content of the tissue
      under investigation.

PMID- 8528127
TI  - Measured and expected Cole parameters from electrical impedance tomographic
      spectroscopy images of the human thorax.
AB  - Electrical impedance tomographic spectroscopy (EITS) images have been recorded
      from a group of 12 normal subjects using frequencies from 9.6 kHz to 1.2 MHz. The
      impedance changes with frequency have been modelled on a pixel by pixel basis to
      produce parametric images as a means of characterizing tissue. The modelling was
      based on the Cole equation. The lungs are seen as areas of high characteristic
      frequency and low time constants SC and RS. The R/S images are much less uniform
      over the region of the lungs. Values characterizing the lung and cardiac regions
      are given. The results appear to be consistent with a model for the lungs whereby
      the model parameters can be related to alveolar structure and composition.

PMID- 8528128
TI  - Quantification in multifrequency tomography.
AB  - The time domain change in human body impedance, in short intervals, usually falls
      into the approximation delta Z << Z0 (delta Z: impedance change, Z0: base
      impedance). This makes it possible to obtain both an image and an estimate of the
      log-conductivity change for the considered section using backprojection
      algorithms. In multifrequency tomography, however, the impedance change can be
      very large, depending on the applied frequencies. In this situation it is
      possible to obtain images using the methods applied in dynamic impedance imaging,
      but the estimate of the impedance change becomes highly non-linear. We have
      developed an algorithm based on the analytical solution of the linearized Poisson
      equation in a curvilinear space formed by the current lines and the equipotential
      lines. In order to set the correct boundary conditions, the current profile under
      the electrodes has been numerically computed. The behaviour of the algorithm has
      been assessed using the voltages obtained by analytically solving the direct
      problem in a circular region with small circular centred and non-centred
      perturbations of different size. The results are compared with those obtained
      using a backprojection algorithm. Although the developed algorithm displays
      higher linearity than a backprojection algorithm, it still shows a dependence on
      the perturbation size and position. This algorithm has been applied to the
      reconstruction of a series of measurements from 8 kHz to 500 kHz made in a sample
      of porcine liver immersed in a saline tank. A Cole-Cole model is fitted to the
      data. The parameters of this model are compared with those calculated from a 4
      wire measurements using a commercial impedance analyser.

PMID- 8528129
TI  - The repeatability and variability of electrical impedance tomography indices of
      pharyngeal transit time in normal adults.
AB  - Two electrical impedance tomography (EIT) indices of pharyngeal transit time have
      been repeatedly measured in 20 normal adults. The time course of change in
      pharyngeal conductivity whilst swallowing 5, 10 and 20 ml boluses was expressed
      either as a full width at 20% maximum (FW20) or as a full width at 50% maximum
      (FW50): the latter could be satisfactorily measured more frequently. Mean
      coefficients of variation for FW20 and FW50 tended to decrease with increasing
      bolus volume but this was statistically significant only for FW50 in men. FW20
      and FW50 were significantly shorter in men than women and increased with
      increasing age. FW50 was significantly smaller when larger bolus volumes were
      swallowed. FW50 was significantly shorter when low-conductivity fluid was used
      and there was an insignificant trend for it to be longer with electrodes in the
      highest position. The amplitude of the conductivity change recorded was
      significantly affected by all factors studied apart from age. If EIT is to be
      used as a technique for monitoring changes in pharyngeal transit time in patients
      with neurogenic dysphagia, repeat examinations should be performed under the same
      conditions and, if possible, large bolus volumes should be used.

PMID- 8528130
TI  - Design considerations and performance of a prototype system for imaging neuronal
      depolarization in the brain using 'direct current' electrical resistance
      tomography.
AB  - The ability to image the impedance changes that accompany neuronal depolarization
      in the brain would constitute a major advance in neuroscience technology.
      Unfortunately, these changes are likely to be small and rapid and so difficult to
      measure. The impedance change at frequencies above 10 kHz, as used by
      conventional EIT systems, may be estimated to be about 0.1%. Modelling indicates
      that a much larger impedance change of about 7% may occur with DC or very-low
      frequency excitation. Difficulties with this approach include a low permissive
      current level and high electrode impedance. We constructed a prototype system
      employing square wave excitation at 5 Hz to evaluate such problems. It was tested
      in a saline-filled tank, recording 4000 frames s-1 at a current level of 50
      microA. After averaging 100 sets of frames, the signal to noise ratio was 40-50
      dB, and reciprocity errors were mostly 10-20%. Images of discrete resistivity
      changes of less than 10% could be obtained, but with significant systematic
      errors. While our prototype would not be suitable for neurophysiological imaging
      as it stands, it has enabled us to determine the modifications that would be
      required to construct a system for this application.

PMID- 8528131
TI  - Determination of optimum injected current patterns in electrical impedance
      tomography.
AB  - The problem of finding the optimum current under different constraints in
      electrical impedance tomography is cast into a non-linear optimization problem.
      Optimum currents are investigated for a two-dimensional cylindrical body with a
      concentric or an eccentric inhomogeneity under the constraints of constant
      dissipated power and constant total injected current. For a concentric
      inhomogeneity, it is shown that the opposite drive results in a better
      distinguishability than the cosine current pattern under the constant-injected
      current constraint. The results for the concentric case are extended to the
      eccentric case directly using the properties of the conformal transformation and
      of the constraints involved. Distinguishability and the minimum detectable object
      size achieved by the optimized currents are compared with the ones achieved by
      the cosine current pattern for conductivity distributions with the concentric and
      eccentric inhomogeneity.

PMID- 8528132
TI  - 2,3-didehydro-2,4-dideoxy-4-guanidino-N-acetyl-D-neuraminic acid (4-guanidino
      Neu5Ac2en) is a slow-binding inhibitor of sialidase from both influenza A virus
      and influenza B virus.
AB  - The effect of 2,3-didehydro-2,4-dideoxy-4-guanidino-N-acetyl-D-neuraminic acid (4
      guanidino-Neu5Ac2en) on the sialidases from influenza virus reassortant X31
      (which contains the sialidase from A/Aichi/2/68) and influenza virus
      B/Beijing/1/87 has been investigated. We find that 4-guanidino-Neu5Ac2en is a
      slow-binding inhibitor of both influenza A and influenza B virus sialidase, and
      that association and dissociation rate constants are almost identical for both
      enzymes. Furthermore, values for these rate constants are independent of whether
      purified enzyme or detergent-treated virus is used in the assays.

PMID- 8528133
TI  - Sequencing of RAPD fragments amplified from the genome of the prokaryote
      Prochlorococcus marinus (prochlorophyta).
AB  - DNA fingerprint patterns from the chlorophyll a and b containing prokaryote
      Prochlorococcus marinus were generated with the RAPD technique using two primers
      derived from repetitive sequence motifs, [(GATA)4 and M13] and a random primer
      (OPB-10]. Five RAPD fragments were reamplified, cloned and sequenced. The clones
      M13/1300 and OPB-10/1100 contained open reading frames, whereas the (GATA)4
      fragments were interrupted by stop codons in all frames indicating their
      noncoding function and possessed a high AT score of 63% and 71%, respectively.
      With the two (GATA)4 clones and the M13/300 clone strain-specific signals were
      obtained in a Southern blot analysis of various Prochlorococcus strains. Clones
      M13/1300 and OPB-10/1100, containing the ORFs, produced RFLPs between the strains
      analyzed. All RAPD fragments are represented as single copy in the genome of
      Prochlorococcus.

PMID- 8528134
TI  - Establishment and characterization of immortalized human coronary endothelial
      cells.
AB  - We established an immortalized cell line from endothelial cells derived from a
      human coronary artery, isolated at autopsy from 76-year-old male, by transfecting
      the cells with origin-minus simian virus 40 DNA. These cells showed SV40 T
      antigen in the nuclei and Ulex europaeus I agglutinin and factor VIII-related
      antigen, as endothelial cell markers, in their cytoplasm. This cell line
      synthesized prostacyclin, tissue-type plasminogen activator (tPA), and
      plasminogen activator inhibitor-1 (PAI-1) as well as produced the proform of
      matrix metalloproteinase 1, which was activated by cultivating the cells with
      plasminogen. These findings reveal that this immortalized endothelial cell line
      retains characteristics of human coronary endothelial cells, indicating that this
      cell line is useful for studying atherogenesis of the coronary artery.

PMID- 8528135
TI  - Experimental evidence for the binemic structure of human chromosomes.
AB  - A binemic model of eukaryotyc chromosome was tested using PCR-amplification of
      some unique genes in individual sperm cells or in human DNA diluted to 1/2 of the
      DNA amount of a haploid cell. According to the model, all the hereditary
      information, including all the unique genes, is represented twice in the haploid
      genome. Backing up of information enhances reliability of the genome by several
      orders of magnitude. Hemoglobin G gene (HBG2) and parathyroid hormone gene (PTH)
      were studied. In the first experimental plot the DNA from one isolated
      spermatozoon was divided into 4 parts and G globin gene was attempted to be
      amplified in all 4 tubes. According to the binemic model the simultaneous
      positive reaction in a pair of tubes should occur in up to 75% of cases and the
      reaction in only one tube from the four should occur in the case of uninemy. In
      the second approach, human DNA was serially deluted to the 1/2 of the haploid
      genome per tube. After amplification, the number of tubes with positive signal
      were counted. According to the unineme model, 3.7 positive reactions from 10 were
      expected. According to the bineme model 6.3 positive reactions from 10 should be
      observed (as follows from Poisson distribution). The results obtained with both
      methods are in accordance with binemic model and are inconsistent with uninemy.

PMID- 8528136
TI  - DNA fragmentation induced in lymphocytes by gamma irradiation or dexamethasone:
      inhibition by diethyldithiocarbamate (DTC), potentiated by zinc.
AB  - Apoptosis is a process of physiological cell death characterized by DNA
      fragmentation, chromatin condensation, loss of membrane asymmetry and cell
      lethality. In the present study, apoptosis induced in thymocytes by dexamethasone
      or gamma irradiation is evaluated by flow cytometry, gel electrophoresis and
      other techniques. Treatment of thymocytes with DTC or zinc shows that these
      products can inhibit radiation- or dexamethasone-induced apoptosis. Moreover, a
      synergistic effect is observed by using associations of both products (5 microM
      DTC + 50 microM ZnSO4): ZnSO4 potentiates the effect of DTC at concentrations for
      which the molecules used separately show a low efficacy. These results indicate
      that DNA fragmentation induced by dexamethasone or irradiation in thymocytes
      share some identical mechanisms.

PMID- 8528137
TI  - Human immunodeficiency virus type 1 integrase stabilizes a linearized HIV-1 LTR
      plasmid in vivo.
AB  - A mammalian expression vector designed for production of HIV-1 integrase was
      found to enhance the stability of a linear reporter plasmid in COS-7 cells. The
      effect is strictly dependent on coexpression of the HIV-1 rev gene and on the
      inclusion of U3 and U5 portions of the HIV-1 LTR in the reporter plasmid.
      Integrase point mutations P109S and D116N drastically reduced stabilization
      whereas T115A and D64A had little or no effect. Immunoblot analysis revealed the
      presence of a 32-34kDa integrase protein in extracts of transfected COS-7 cells
      and of wild type and mutant integrase proteins at comparable levels. We conclude
      that integrase acts in trans in COS-7 cells, possibly by binding to the HIV-1 LTR
      in the plasmid. This transfection system may be useful for studying factors that
      stabilize the HIV-1 DNA genome prior to its integration into the host cell
      chromosome.

PMID- 8528138
TI  - Bam HI cleaves the self complementary dodecamer d-CGCGGAGCCGCG, before the two
      G's and possibly binds in the DNA major groove.
AB  - Oligodeoxynucleotides with GT or GA mispairs within the Bam HI recognition
      sequence (GGATCC), have been prepared. Binding and cleavage of the native vis a
      vis the mismatch substrates by Bam HI are analysed. UV melting curves and CD
      spectra of the oligomers suggest a double stranded B-DNA conformation. The enzyme
      Bam HI binds with varying affinities to the oligomers except the one with the GT
      wobble base pair. Bam HI cleaves the cognate sequence, GGATCC, between the two
      Guanines but cleaves GGAGCC before the guanines. The unusual cleavage is due to a
      local distortion in the DNA structure. Kinetic analysis of the cleavage reactions
      using the 35S labeled hexadecamers, d-ATGGCGGATCCGCCAT and d-ATGGCGGAGCCGCCAT, as
      substrates gives Km values 11.08 nM and 1.16 nM with corresponding Kcat of 11.04
      and 0.62 min-1 respectively. The results are consistent with the binding of Bam
      HI in the major groove.

PMID- 8528139
TI  - Functional domain mapping using M13 deletions.
AB  - We describe a convenient approach for concomitant functional characterization of
      peptide domains (monoclonal antibody epitopes, receptor-ligand, DNA-protein, and
      protein-protein interaction sites, etc) encoded by the sequential series of
      overlapping M13 subclones generated for nucleotide sequence determination of a
      new cDNA. We have employed this method to rapidly map the location and amino acid
      sequence of an epitope-containing domain within a polypeptide encoded by a newly
      isolated cDNA.

PMID- 8528140
TI  - Molecular cloning and expression in S. cerevisiae of two exochitinases from
      Trichoderma harzianum.
AB  - The synthetic exochitinase substrate 4-methylumbelliferyl N-acetylglucosamine was
      used to identify seven full-length exochitinase-encoding cDNAs from a Trichoderma
      harzianum cDNA library by expression in yeast. The cDNA clones represented
      transcripts of two exochitinase genes, designated as exc1 and exc2, which cross
      hybridized under moderate stringency conditions in genomic Southern blots. The
      exc1 cDNA encodes a 578 amino acid polypeptide showing 72% similarity to the exc2
      encoded 602-residue polypeptide. The deduced exochitinase amino acid sequences
      were found to be homologous with mammalian and fungal hexosaminidases as well as
      a bacterial chitobiosidase. The substrate specificity of the recombinant enzymes
      expressed in S. cerevisiae indicates that the enzymes are N
      acetylglucosaminidases releasing single N-acetylglucosamine residues from the non
      reducing end of the chitin substrate.

PMID- 8528141
TI  - Protein kinase C phosphorylates two of the four known syndecan cytoplasmic
      domains in vitro.
AB  - The transmembrane heparan sulfate proteoglycans of the syndecan family are
      implicated to participate in several cellular reactions which are dependent on
      protein kinase C. We have used an in vitro assay to assess whether any of the
      Peptides corresponding to the complete cytoplasmic domains of rat syndecans 1
      through 4 were used as substrates for the enzyme. The syndecan-2 (fibroglycan)
      and syndecan-3 (N-syndecan) peptides were both found to be phosphorylated by
      protein kinase C with Kms of 15 +/- 3 microM and 85 +/- 25 microM, respectively,
      while the syndecan-1 and -4 peptides were not phosphorylated under the conditions
      used. The sites of in vitro phosphorylation for syndecans-2 and -3 were localized
      to ser-197 and ser-339, respectively. Thus, among 13 available sites (serines and
      threonines) in the four peptides, two were selectively modified by the enzyme.
      The specificity and the kinetics of the reactions indicate that the cytoplasmic
      domains of syndecan-2 and -3 are likely to be physiological substrates for
      protein kinase C.

PMID- 8528142
TI  - Elevated levels of the chromosomal protein HMG 17 in chronic myelogenic leukemia.
AB  - The High Mobility Group protein HMG 17 has been isolated from human leukemia
      cells obtained from patients with chronic myelogenic leukemia (CML). The level of
      expression of HMG 17 was investigated Human leukemia cells have three times more
      HMG 17 than normal human leukocytes. Three other malignant tissues were also
      compared. Two of these breast adenocarcinoma and other intestine- also exhibit
      higher amounts of HMG 17. The elevated expression of HMG 17 suggests that the
      level of the protein may be associated with rates of cellular proliferation.

PMID- 8528143
TI  - Modulation of transcriptional activity of the chicken ovalbumin gene promoter in
      primary cultures of chicken oviduct cells: effects of putative regulatory
      elements in the 5'-flanking region.
AB  - With primary cultures of chicken oviduct cells, we tested functional roles in the
      ovalbumin gene transcription of NF-1 like factor binding element, half estrogen
      response-element direct repeat, and chicken ovalbumin upstream promoter residing
      in the 5'-flanking region of the chicken ovalbumin gene. The three putative
      regulatory elements were fused upstream to the chloramphencol acetyltransferase
      reporter gene driven by the chicken ovalbumin gene promoters, and transient gene
      expression was measured in primary cultured oviduct cells. The results indicated
      that neither the NF1 binding element nor the ovalbumin upstream promoter showed
      any enhancer-like activity. In addition, although the half estrogen response
      element direct repeat enhanced transcriptional activity of the ovalbumin gene
      promoter, it completely deprived the ovalbumin promoter of estrogen dependency.
      We concluded, therefore, that the biological significance of these three putative
      regulatory elements in the homologous chicken oviduct cell system might be
      different from those previously reported in heterologous systems.

PMID- 8528144
TI  - Purification and characterization of hepatic oligosaccharyltransferase.
AB  - Oligosaccharyltransferase transfers a preformed oligosaccharide from a dolichol
      carrier molecule to specific asparaginyl residues of proteins synthesized in the
      endoplasmic reticulum. We have isolated a protein complex with this activity from
      chicken liver microsomes with 850 fold purification. The purification procedure
      involved removal of peripheral and lumenal proteins, solubilization of the
      membranes by non-ionic detergent and glycerol gradient centrifugation. The
      complex was purified further by ion-exchange and gel filtration chromatography.
      SDS-PAGE analysis of the final preparation revealed 3 major protein bands, two
      bands with an approximate molecular weight of 65-kDa and one band of
      approximately 50-kDa. Endoglycosidase H digestion of the purified subunits
      indicated the presence of carbohydrate on the 65-I subunit. No carbohydrate was
      detected in the 65-II subunit or the 50-kDa subunit. Amino acid sequence analysis
      of the intact protein subunits and internal peptides generated by cynogen bromide
      digestion, identified the 65-kDa subunits as ribophorin I and II. The 50-kDa
      subunit has 25% homology with a yeast membrane protein (Wbplp) which is essential
      for oligosaccharyltransferase activity in Saccharomyces cerevisiae.

PMID- 8528145
TI  - Metal content and conformation of the metalloprotease from the marine sponge
      Spheciospongia vesparia.
AB  - We have recently purified a protease from the marine sponge Spheciospongia
      vesparia. It consists of a single nonglycosylated polypeptide chain with a
      molecular weight of 29 600 and has one free thiol group. Metal analysis revealed
      the presence of zinc at 2.02 +/- 0.05 g-atoms per mole of protein, as measured by
      atomic absorption spectroscopy. The circular dichroism spectrum in the far UV
      region (183-259 nm) indicates that the sponge protease contains appreciable
      amounts of beta sheet. This enzyme resembles very much an aminopeptidase from
      Aeromonas proteolytica concerning activity and some physiochemical
      characteristics.

PMID- 8528146
TI  - Involvement of phosphatidylinositol 3-kinase in stimulation of glucose transport
      by growth factors in 3T3-L1 adipocytes.
AB  - Activation of phosphatidylinositol 3-kinase (PI 3-kinase) appears to be part of
      the signaling mechanism by which insulin stimulates cellular glucose uptake. We
      have investigated the involvement of PI 3-kinase in the regulation of glucose
      uptake in 3T#-L1 adipocytes by comparing the effects of platelet-derived growth
      factor (PDGF), epidermal growth factor (EGF), and insulin. Stimulation of
      [14C]deoxyglucose uptake by PDGF and EGF was 29% and 70%, respectively, while
      that by insulin was 5-fold. Wortmannin, a PI 3-kinase inhibitor, completely
      blocked the effects of all three agonists. The relative effects of the growth
      factors on phosphatidlyinositoltriphosphate (PIP3) synthesis were also
      determined. Insulin caused a large increase in this phosphoinositide. The effect
      of PDGF was much smaller, in fact barely detectable, while EGF had no detectable
      effect. The results suggest a role for PI 3-kinase in stimulation of glucose
      uptake by PDGF and EGF. However, the degree of PI 3-kinase by these growth
      factors appears to be much smaller than that by insulin, consistent with smaller
      stimulations of glucose transport.

PMID- 8528147
TI  - PP2C phosphatase activity is coupled to cAMP-mediated pathway in rat parotid
      acinar cells.
AB  - A 26 kDa particulate protein is phosphorylated during stimulation of amylase
      secretion by a beta-adrenergic agonist in the rat parotid gland. Previous study
      has shown that PP2C phosphatase is involved in dephosphorylation of this 26 kDa
      protein [Yokoyama, N. et al. (1994) Biochem. Biophys. Res. Commun. 200, 497-503].
      In this study, immunotransblot analysis using anti-PP2C phosphatase antibody
      showed that PP2C phosphatase was found prominently in the cystolic fractions and
      less in secretory granule membranes. When cells were stimulated by isoproterenol,
      cytosolic PP2C phosphatase activity increased to 145% at 5 min and returned to
      basal level at 30 min. Forskolin increased PP2C phosphatase activity. H89
      inhibited increase of PP2C phosphatase activity following beta-adrenergic
      stimulation. These results suggest that PP2C phosphatase activity is regulated by
      cAMP-mediated signaling following beta-adrenergic stimulation and participates in
      dephosphorylation of this 26 kDa protein.

PMID- 8528148
TI  - Reduction of cis-platinum induced nephrotoxicity by zinc histidine complex : the
      possible implication of nitric oxide.
AB  - Cisplatin is a prominent member of the effective broad spectrum antitumor drugs.
      The clinical usage of cisplatin is, however, restricted due to some adverse side
      effects including renal toxicity. The present study demonstrates the protective
      effect of a Zinc-chelate of histidine, [Zn-Hist], against cisplatin induced
      nephrotoxicity and gastrointestinal toxicity as shown by decreases in BUN,
      creatinine and lower incidence of diarrhoea. The observed inhibition in cisplatin
      induced renal and hepatic lipid peroxidation by [Zn-Hist] pretreatment, suggests
      an importance for Zn in stabilisation of membrane integrity probably through the
      displacement of the redox-active metals that may be responsible for inducing
      peroxidative damage at target sites. The findings also suggest that cisplatin may
      play biochemical role in arginine-metabolism including nitric oxide (NO)
      production.

PMID- 8528149
TI  - Effects of P2-purinoceptor antagonists on ecto-nucleotidase activity of guinea
      pig vas deferens cultured smooth muscle cells.
AB  - Ecto-nucleotidase activity was studied on primary cultures of guinea-pig vas
      deferens smooth muscle cells by measuring the inorganic phosphate (Pi) production
      using ATP as a substrate. The ecto-nucleotidase was insensitive to ouabain,
      oligomycin, sodium azide, p-nitrophenyl phosphate and B-glycerophosphate. Enzyme
      activity was highly dependent on either Ca2+ or Mg2+. Antagonists of P2X
      purinoceptors, pyridoxalphosphate-6-azophenyl-2',4'- disulphonic acid, 4'4'
      diisothiocyanatostilbene-2'2'- disulphonate, suramin and pyridoxal-5-phosphate,
      significantly inhibited ecto-nucleotidase activity. In contrast, the P1
      purinoceptor antagonists, 8-p-sulphophenyl theophylline and 1,3-dipropyl-8
      cyclopentylxanthine, did not affect the enzyme activity. Thus, when P2
      purinoceptors are studied by testing agonists and antagonists potencies, the
      inhibition of ecto-nucleotidase activity by currently available P2-purinoceptor
      antagonists should be taken into account.

PMID- 8528150
TI  - Identification of a novel ATP-dependent proteolytic activity in mitochondrial
      intermembrane space.
AB  - The formation of primary amines via proteolysis was monitored in isolated rat
      liver, kidney cortex and heart mitochondria in the presence and in the absence of
      ATP. The highest proteolytic activity was detected in kidney cortex mitochondria
      with about 120 nmoles primary amines/hour x mg protein. The formation rates of
      liver mitochondria amounted to about 100 nmoles primary amines/hour x mg protein
      and in heart mitochondria about 60 nmoles primary amines/hour x mg protein. In
      all mitochondria investigated an ATP-dependent proteolysis of 20-40 nmoles
      primary amines/hour x mg protein was detected. The effects of various protease
      inhibitors were tested in rat liver mitochondria and thiol-specific reagents
      showed a 35-70% inhibition. The ATP stimulable portion of proteolysis was blocked
      by hemin, a known inhibitor of ATP-dependent proteases. The localization of the
      proteolytic activity was tested by fractionation of the compartments of rat liver
      mitochondria using the flourogenic peptide suc-Leu-Leu-Val-Tyr-MCA as substrate.
      About 90% of the ATP-dependent peptide cleavage activity were found in the
      mitochondrial intermembrane space. The characteristics of the enzyme were
      compared to those of other known mitochondrial ATP-dependent proteases and it was
      concluded that it represents a novel proteolytic system of the intermembrane
      space.

PMID- 8528151
TI  - Pyrimidine moiety of thiamin is biosynthesized from pyridoxine and histidine in
      Saccharomyces cerevisiae.
AB  - The isotopes of [6-13C]- and [5'-2H2]pyridoxine were incorporated efficiently
      into the pyrimidine moiety of thiamin in S. cerevisiae. The mass fragmentation
      pattern showed that the C-6 and H-5' atoms of pyridoxine were incorporated into
      the C-6, and H-5' atoms of the pyrimidine, respectively. These findings, along
      with out previous results, show that the C-2', C-2, N-1, C-6, C-5, and C-5' unit
      of the pyrimidine are derived from the C-2', C-2, N-1, C-6, C-5 and C-5' unit of
      pyridoxine, and that pyrimidine is biosynthesized from pyridoxine and histidine.

PMID- 8528152
TI  - Fluorescence spectroscopic study of the interaction of adenine and nucleotide
      with trichosanthin.
AB  - Trichosanthin (TCS) is an N-glycosidase that can attack the 28s rRNA of the
      ribosome at a highly conserved adenine residue. The interactions of adenine and
      its derivative nucleotides with TCS are reported. The fluorescence of Trp 192 of
      TCS is sensitive to the proximity of adenine, and produces a marked red shift
      indicative of trytophan in a more hydrophilic environment. By contrast AMP and
      ATP quench the maximal emission at 328nm. The binding of the adenine and ATP with
      TCS result in lower tryptophan accessibility to the quencher acrylamide, but
      higher tryptophan accessibility to the quencher iodide, while AMP caused higher
      tryptophan accessibility to acrylamide, and lower tryptophan accessibility to
      iodide. Also, the binding of nucleotides induces tryptophan heterogeneity in the
      protein. These findings lead us to propose that binding of nucleotides and
      adenine base cause different microenvironmental changes of the tryptophan
      residue, and Trp 192 may be involved in the active site of TCS.

PMID- 8528153
TI  - Enzymic hydrolysis of raffinose and stachyose in soymilk by alpha-galactosidase
      from Gibberella fujikuroi.
AB  - The use of intracellular alpha-galactosidase from Gibberella fujikuroi to remove
      raffinose and stachyose in soymilk was studied. The optimum conditions for the
      enzymic hydrolysis of raffinose and stachyose was pH 5.5 to 6.0 at 55 degrees C.
      Alpha-galactosidase showed optimum activity at pH 5.0 and 50 degrees C with the
      substrate p-nitrophenyl-alpha-D-galacto-pyranoside (PNGP). The enzyme showed no
      detectable loss of activity when held more than 8 hr at 50 degrees C. Thin layer
      chromatography (TLC) revealed the following composition of oligosaccharides in
      local soybean variety: sucrose, 5.53%; raffinose, 1.95%; and stachyose, 6.1%.
      Investigation by TLC showed complete hydrolysis of raffinose and stachyose in 3
      hr. HPLC analysis of hydrolyzate indicated complete hydrolysis of stachyose, and
      more than 60% hydrolysis of raffinose in 2.5 hr.

PMID- 8528154
TI  - Hypoxia induces HSP 70 gene expression in human hepatoma (HEP G2) cells.
AB  - Populations of cells within solid tumours are exposed to low oxygen
      concentrations. The mechanism by which tumour cells tolerate such hypoxia is
      unknown but it may parallel responses to other types of cellular stress. We
      investigated the effect of oxygen on steady state levels of inducible heat shock
      protein 70 mRNA in cultured human hepatoma cells. Northern blot analysis
      demonstrated that hypoxia increased HSP 70 mRNA levels within 3 hours, with a
      transient 12-fold increase at 6 hours compared with normoxia. We also showed that
      heat shock induced a 20-fold increase in HSP 70 mRNA. This data suggests that
      HSPs may be important in tumour progression by protecting cells from hypoxic
      stress.

PMID- 8528155
TI  - Guanidine thiol--a new activator of soluble guanylate cyclase with
      antihypertensive and antiaggregatory properties.
AB  - Effects of aminoethylisothiuronium bromide (AET), known as radioprotector, on
      human platelet soluble guanylate cyclase and on ADP-induced human platelets
      aggregation were studied. It was shown that AET - in Tris buffer and at certain
      pH values - is converted, via transguanidine rearrangement, to
      mercaptoethylguanidine. The latter contains in its molecule both the guanidine
      and SH groups which act as donor and acceptor of nitric oxide (NO), respectively.
      It was demonstrated that AET, after its rearrangement to mercaptoethylguanidine,
      is able to activate human platelet soluble guanylate cyclase, as well as to
      inhibit ADP-induced human stimulatory effect of AET is dependent on the
      effectiveness of its transguanidine rearrangement to mercaptoethylguanidine. The
      molecular mechanism of the hypotensive by - effect of AET is proposed.

PMID- 8528156
TI  - Building a structured model of a complex pharmacokinetic system with time delays.
AB  - This paper presents a description of the procedure for building a structured
      model of a complex pharmacokinetic system on using its transfer function. The
      example employed is that of the pharmacokinetic system based on gentamicin plasma
      concentrations after intravenous and intratracheal administration to guinea pigs,
      describing the pathway of the drug into the systemic circulation after the
      extravascular injection mentioned. The structured model selected consisted of a
      submodel of a proportional linear subsystem, two submodels of simple linear
      dynamic subsystems with time constants of 0.135 +/- 0.065 hr (95% I.C.) and 0.052
      +/- 0.049 hr, and two submodels of parallel subsystems with time delays of 0.25
      +/- 0.046 hr and 1.135 +/- 0.288 hr, connected in serial. Two estimates of the
      mean residence time of the total amount of gentamicin in the system, i.e., 0.347
      and 0.335 hr, were obtained, based on the system frequency and structured model,
      respectively. From the methodological point of view, our paper demonstrates the
      efficiency of combination of modelling in the frequency and in the time domain,
      designed to facilitate studies of pharmacokinetic systems.

PMID- 8528157
TI  - Dynamics and bifurcations of two coupled neural oscillators with different
      connection types.
AB  - In this paper we present an oscillatory neural network composed of two coupled
      neural oscillators of the Wilson-Cowan type. Each of the oscillators describes
      the dynamics of average activities of excitatory and inhibitory populations of
      neurons. The network serves as a model for several possible network
      architectures. We study how the type and the strength of the connections between
      the oscillators affect the dynamics of the neural network. We investigate,
      separately from each other, four possible connection types (excitatory-
      >excitatory, excitatory-->inhibitory, inhibitory-->excitatory, and inhibitory-
      >inhibitory) and compute the corresponding bifurcation diagrams. In case of weak
      connections (small strength), the connection of populations of different types
      lead to periodic in-phase oscillations, while the connection of populations of
      the same type lead to periodic anti-phase oscillations. For intermediate
      connection strengths, the networks can enter quasiperiodic or chaotic regimes,
      and can also exhibit multistability. More generally, our analysis highlights the
      great diversity of the response of neural networks to a change of the connection
      strength, for different connection architectures. In the discussion, we address
      in particular the problem of information coding in the brain using quasiperiodic
      and chaotic oscillations. In modeling low levels of information processing, we
      propose that feature binding should be sought as a temporally coherent phase
      locking of neural activity. This phase-locking is provided by one or more
      interacting convergent zones and does not require a central ?top level?
      subcortical circuit (e.g., the septo-hippocampal system). We build a two layer
      model to show that although the application of a complex stimulus usually leads
      to different convergent zones with high frequency oscillations, it is
      nevertheless possible to synchronize these oscillations at a lower frequency
      level using envelope oscillations. This is interpreted as a feature binding of a
      complex stimulus.

PMID- 8528158
TI  - Idiotypic regulation of B cell differentiation.
AB  - We study the equilibrium properties of idiotypically interacting B cell clones in
      the case where only the differentiation of B cells is affected by idiotypic
      interactions. Furthermore, we assume that clones may recognize and be stimulated
      by self antigen in the same fashion as by anti-antibodies. For idiotypically
      interacting pairs of non-autoreactive clones we observe three qualitatively
      different dynamical regimes. In the first regime, at small antibody production an
      antibody-free fixed point, the virgin state, is the only attractor of the system.
      For intermediate antibody production, a symmetric activated state replaces the
      virgin state as the only attractor of the system. For large antibody production,
      finally, the symmetric activated state gives way to two asymmetric activated
      states where one clone suppresses the other clone. If one or both clones in the
      pair are autoreactive there is no virgin state. However, we still observe the
      switch from an almost symmetric activated state to two asymmetric activated
      states. The two asymmetric activated states at high antibody production have
      profoundly different implications for a self antigen which is recognized by one
      of the clones of the pair. In the attractor characterized by high autoantibody
      concentration the self antigen is attacked vigorously by the immune system while
      in the opposite steady state the tiny amount of autoantibody hardly affects the
      self antigen. Accordingly, we call the first state the autoimmune state and the
      second the tolerant state. In the tolerant state the autoreactive clone is down
      regulated by its anti-idiotype providing an efficient mechanism to prevent an
      autoimmune reaction. However, the antibody production required to achieve this
      anti-idiotypic control of autoantibodies is rather large.

PMID- 8528160
TI  - The mathematics of radiation target analyses.
AB  - Radiation target theory has been extended to complex biochemical systems.
      Mathematical analyses are presented for multiple forms of biological active
      proteins, for the presence of large inhibitors or activators, for compounds which
      regulate rate or affinity and for multiple-step reactions. Several predictions of
      these models have been verified experimentally.

PMID- 8528159
TI  - Electrotonic coupling between two CA3 hippocampal pyramidal neurons: a
      distributed cable model with somatic gap-junction.
AB  - A model of a pair of electrotonically coupled CA3 hippocampal pyramidal neurons
      is presented. Each neuron is represented by a tapered equivalent cable attached
      to an isopotential soma. The synaptic potential in a neuron soma is determined as
      a consequence of electrical coupling to another soma that receives a synaptic
      input on its dendritic tree. Estimates of the coupling resistances, soma input
      resistances and soma-to-dendritic tree conductance ratio show that a substantial
      current may arise in a neuron as a consequence of synaptic activity in a neuron
      coupled to it. The small increase in decay time due to coupling in the model
      indicates that actual coupling is between more than just pairs of neurons.

PMID- 8528161
TI  - The potassium A-current, low firing rates and rebound excitation in Hodgkin
      Huxley models.
AB  - It is widely believed, following the work of Connor and Stevens (1971, J.
      Physiol. Lond. 214, 31-53) that the ability to fire action potentials over a wide
      frequency range, especially down to very low rates, is due to the transient,
      potassium A-current (IA). Using a reduction of the classical Hodgkin-Huxley
      model, we study the effects of IA on steady firing rate, especially in the near
      threshold regime for the onset of firing. A minimum firing rate of zero
      corresponds to a homoclinic bifurcation of periodic solutions at a critical level
      of stimulating current. It requires that the membrane's steady-state current
      voltage relation be N-shaped rather than monotonic. For experimentally based
      generic IA parameters, the model does not fire at arbitrarily low rates, although
      it can for the more atypical IA parameters given by Connor and Stevens for the
      crab axon. When the IA inactivation rate is slow, we find that the transient
      potassium current can mediate more complex firing patterns, such as periodic
      bursting in some parameter regimes. The number of spikes per burst increases as
      gA decreases and as inactivation rate decreases. We also study how IA affects
      properties of transient voltage responses, such as threshold and firing latency
      for anodal break excitation. We provide mathematical explanations for several of
      these dynamic behaviors using bifurcation theory and averaging methods.

PMID- 8528162
TI  - Malignant diseases after bone marrow transplantation: the case for tumor banking
      and continued reporting to registries. EBMT Late-Effects Working Party.

PMID- 8528163
TI  - Stem cell transplantation for severe autoimmune diseases: new proposals but still
      unanswered questions.
AB  - An extensive series of experimental investigations has shown that both inherited
      and induced autoimmune diseases in laboratory animals may be transferred and,
      conversely, cured by stem cell transplantation. In man, the evidence is mainly
      anecdotal, originating both from the transmission of autoimmune conditions
      following allogeneic BMT from carrier donors to non-autoimmune recipients
      transplant-requiring diseases, and from the resolution of autoimmune diseases
      (mainly rheumatoid arthritis) of the recipients after allogeneic BMT from healthy
      donors. Will it be possible to cure severe autoimmune diseases with powerfully
      immunosuppressive conditioning regimens followed by the administration of
      hematopoietic stem cells? If the reconstitution of a naive immune system is
      necessary, allogeneic stem cells will be necessary, but the procedure is still
      saddled with its attending problems, with TRM in the foreground. When utilizing
      autologous stem cells in conjunction with TCD the patients' tolerance will be
      significantly better, but remissions are to be anticipated rather than cures.
      However, some special manipulations may be expected to ameliorate results in
      those selected autoimmune patients not or badly responding to conventional
      immunosuppressive therapy, for whom this type of treatment can be offered.

PMID- 8528164
TI  - Autologous bone marrow transplantation for acute myeloid leukemia in first
      remission: identification of modifiable prognostic factors.
AB  - Seventy-four consecutive patients (median age 31 years) with acute myeloid
      leukemia (AML) undergoing unpurged autologous bone marrow transplantation (ABMT)
      in first remission after melphalan and total-body irradiation were studied to
      assess the impact of 14 modifiable and non-modifiable prognostic factors on
      relapse and disease-free survival. Thirty patients were alive in continuous CR at
      a median of 37.5 months (range 3-94), 14 died of transplant-related toxicity at a
      median of 5.5 months (range 0.5-18), and 30 relapsed at a median of 7.5 months
      (range 2-23). The actuarial 5-year probabilities of relapse and disease-free
      survival were 53.4 and 34.2%, respectively. On multivariate analysis,
      administration of two or more courses of consolidation chemotherapy prior to the
      harvest and transplant was found to be the most significant factor associated
      with decreased relapse (relative risk 2.62, P = 0.0012) and improved disease-free
      survival (relative risk 3.03, P = 0.0009). A nucleated cell dose of > 2 x
      10(8)/kg improved disease-free survival (relative risk 2.17, P = 0.045) by
      decreasing transplant-related mortality (P = 0.047). We conclude that adequate
      consolidation of remission before ABMT is the most important factor associated
      with continuing remission after ABMT. Short-term therapy of AML with two courses
      of consolidation therapy followed by ABMT requires comparison with repeated
      courses of intensive chemotherapy for efficacy and cost-effectiveness.

PMID- 8528165
TI  - High-dose carboplatin, etoposide and cyclophosphamide with autologous bone marrow
      transplantation for the treatment of advanced malignancies: a phase I study.
AB  - Carboplatin is a platinum-derivative widely used in conditioning regimens with
      ABMT, particularly in combination with cyclophosphamide and etoposide, drugs
      which co-express synergism in vitro. The objective of this study was to determine
      the maximum tolerated dose (MTD) of this combination. Thirty-four patients with
      refractory lymphoid or solid tumors were treated in a dose-escalation study with
      continuous infusion carboplatin (1.2-2 g/m2) on days -7 to -4, etoposide (1.2-2.4
      g/m2) on days -7 to -5 and cyclophosphamide (120 mg/kg) given in two dose
      schedules: (1) day -3, -2; (2) day -9, -8. Autologous bone marrow or peripheral
      blood stem cells were infused on day 0. Mucositis/enterocolitis was dose
      limiting. In addition, severe cardiac dysfunction occurred in schedule 1 but not
      in schedule 2. Renal dysfunction occurred in the setting of fungemia, respiratory
      failure and congestive heart failure, and did not correlate with carboplatin
      dose. Hepatic and pulmonary dysfunction were minimal. The MTD was etoposide 2.1
      g/m2 and carboplatin 2.0 g/m2, in combination with cyclophosphamide (120 mg/kg)
      on schedule 2. Responses were seen in 16 of 19 patients with measurable disease.
      Seven patients are disease-free survivors 50-60+ months post-ABMT. This study
      defines the MTD of carboplatin when combined with etoposide and cyclophosphamide
      in patients with adequate renal function and suggests significant anti-tumor
      activity.

PMID- 8528166
TI  - Phase I-II study of interleukin-2 after high-dose chemotherapy and autologous
      bone marrow transplantation in poorly responding neuroblastoma.
AB  - Despite intensification of treatment with high-dose chemotherapy (HDC) and
      autologous bone marrow transplantation (AMBT), the prognosis of poorly responding
      metastatic neuroblastoma remains bad. Recombinant IL-2 (rIL-2) was used after
      ABMT to enhance the immune response against the tumor and thereby to improve
      survival of these patients. In this study, five courses of rIL-2 were
      administered as a continuous intravenous infusion every 2 weeks, the first course
      lasting 5 days, and the other four 2 days. rIL-2 treatment was to begin within
      120 days of BMT. This study demonstrates the feasibility of rIL-2 soon after HDC
      and ABMT. The maximum tolerated dose (MTD) was 12 x 10(6) U/m2/day. Clinical
      toxicity was similar to that observed in adults, moderately increased by the
      proximity of ABMT; in a previous study we demonstrated that the MTD in non
      grafted children was 18 x 10(6) U/M2/day. Nevertheless, half of the patients were
      not able to receive rIL-2 therapy after ABMT, and only 6/12 received 100% of the
      planned dose, mainly because of thrombocytopenia. If peripheral stem cell
      transplantation is demonstrated to enhance platelet recovery, more patients could
      be treated with rIL-2 with the present schedule. Earlier administration of low
      dose rIL-2 after BMT associated with ex vivo rIL-2 treatment of the graft could
      be a more valid way of using rIL-2 to improve survival.

PMID- 8528167
TI  - Allogeneic bone marrow transplantation following a busulfan-based conditioning
      regimen in young children with acute lymphoblastic leukemia: a Cooperative Study
      of the Societe Francaise de Greffe de Moelle.
AB  - A subgroup of children with ALL remains at high risk of relapse despite the
      administration of intensive chemotherapeutic protocols and may benefit from
      allogeneic BMT. The cytoreductive regimen used most often combines TBI with
      cyclophosphamide. Nevertheless, miscellaneous long-term sequelae have been
      consequent upon radiotherapy, especially in young children. This retrospective
      multicentric study analyzes the outcome of children with ALL under 4 years of age
      receiving an HLA-genoidentical BMT following a radiation-free preparative
      regimen. A busulfan-based regimen with cyclophosphamide or melphalan +/-
      etoposide +/- cytarabine was given to 21 children (median age: 28 months, range 6
      48). Sixteen patients with initial poor prognostic factors were transplanted in
      first complete response (CR) and five patients in relapse or second CR. With a
      median follow-up of 47 months, the results show an overall 4-year DFS of 61.1%.
      Leukemic recurrence was observed in eight patients. The preparative regimen was
      well-tolerated and there were no transplant-related deaths. A busulfan-based BMT
      preparative regimen may be a therapeutic alternative to TBI-containing regimens
      in young children. Efforts are currently aimed at reducing the relapse rate in
      these children by optimizing the tumoricidal potential of chemotherapy and the
      graft-versus-leukemia effect of allogeneic BMT.

PMID- 8528169
TI  - Kinetics of paraprotein clearance after autografting for multiple myeloma.
AB  - The kinetics of paraprotein clearance after autografting for multiple myeloma
      have not been described. We studied 33 myeloma patients in plateau phase with
      detectable paraprotein (3-34 milligrams, median 10 milligrams) at the time of
      ABMT who received melphalan (200 mg/m2) and methylprednisolone (1.5 g x 5) for
      conditioning. Fifteen patients received interferon-alpha post-transplant as part
      of a randomized study. Twenty-four of 33 (72.7%) patients eventually cleared the
      paraprotein at a median of 47 days (range 5-783) post-transplant. The probability
      of clearance was lower (46.7 vs 94.4%, P = 0.004) and the time taken to clear
      paraprotein longer (142 vs 29 days, P = 0.003) in patients with a higher level (>
      10 milligrams) at the time of the transplant. However, clearance occurred within
      6 months in 23 of 24 (95.8%) patients who ultimately cleared the paraprotein.
      Interferon-alpha did not influence the clearance of paraprotein. We conclude that
      after autografting for myeloma, the time taken to clear paraprotein is longer and
      the probability of clearance lower with higher levels at the time of ABMT, and
      most patients who eventually clear the paraprotein do so within 6 months. Because
      the probability of clearing paraprotein (and thus attaining remission) in
      patients with detectable paraprotein 6 months post-transplant is low, a decision
      about further treatment may be made at this point.

PMID- 8528168
TI  - Haploidentical bone marrow transplantation from mother to child with advanced
      leukemia.
AB  - Use of the mother as mismatched marrow donor was assessed in 19 children with
      advanced leukemia. Patients were homogeneous for HLA incompatibility, age, donor,
      and conditioning regimen, and stage of disease. All received busulfan and
      cytoxan, combined with unmodified donor marrow, ALG given before and after
      transplant, and short MTX and cyclosporine as GVHD prophylaxis. Survival, LFS,
      and relapse respectively were 26, 26, and 33%. Incidence of overall and severe
      acute GVHD was 58 and 32%, respectively. Four patients had failure of
      engraftment, and two of these are alive with autologous reconstitution in
      complete remission. Probability of rejection was 21%. Results of haploidentical
      transplants were compared with those of children with advanced leukemia treated
      at the same institution, who received marrow from HLA-identical siblings. The
      probability of long-term leukemia-free survival was similar in the two groups. We
      thus propose using the mother as an alternative marrow donor in children with
      advanced leukemia.

PMID- 8528170
TI  - Comparison of anxiety, pain and discomfort in two procedures of hematopoietic
      stem cell collection: leukacytapheresis and bone marrow harvest.
AB  - The aim of this study was to compare anxiety, pain and discomfort of cancer
      patients submitted to either peripheral blood progenitor cell collection (PBPCC)
      or bone marrow harvest (BMH). Patients, randomized (7/1993-2/1994), in view of
      autograft, to receive the first procedure or the second one, completed self
      administered questionnaires. Anxiety was assessed by the State Trait Anxiety
      Inventory and pain using visual analogical scale (VAS) and McGill Pain
      questionnaire. Before the procedure, BMH patients (n = 25) experienced more
      anxiety (P < 0.01) and more trouble or inconvenience for having to come and stay
      at the hospital (P < 0.0001) than PBPCC patients (n = 40). Pain due to BMH is
      significantly higher than pain induced by PBPCC (P < 0.001 for VAS and total
      McGill score). However, patients submitted to PBPCC with a femoral catheter (n =
      19) had significantly higher total McGill scores and sensory sub-scores than
      patients without it (n = 21). At discharge from the hospital, PBPCC patients
      expressed more positive judgements towards the collection procedure than BMH
      patients. These results suggest that a better patient acceptability of high-dose
      chemotherapy followed by autograft may be obtained by substituting PBPCC for BMH
      for stem cell collection.

PMID- 8528171
TI  - Very primitive hemopoietic cells (LTC-IC) are present in Philadelphia negative
      cytaphereses collected during early recovery after chemotherapy for chronic
      myeloid leukemia (CML).
AB  - We have previously demonstrated that Philadelphia negative (Ph-ve) hemopoietic
      cells can be collected by leukaphereses after an acute leukemia-like chemotherapy
      during the early hemopoietic recovery in patients with chronic myeloid leukemia
      (CML). In this study we have evaluated whether these collections contain very
      primitive hemopoietic cells defined as 'long-term culture initiating cells' (LTC
      IC) and whether these cells belong to the Ph-positive or Ph-negative population.
      Twenty-eight out of 76 cytaphereses collected in 15 patients with CML proved to
      contain Ph-ve cells only (six patients), 21 showed only Ph+ve cells (five
      patients), and 27 a mixture of Ph+ve and Ph-ve cells (four patients). In
      cytaphereses containing Ph-ve cells only, we found variable numbers of LTC-ICs,
      more consistently when we mobilized patients in the first 3 months from
      diagnosis. In three cases cytogenetic analysis on LTC-ICs and CFU-GM confirmed
      results obtained on fresh samples. Ph-positive collections were devoid of LTC-ICs
      except for 2/21 samples. However, their cytogenetic analysis revealed a small
      number of Ph-negative progenitors. LTC-ICs were randomly detected in mixed (Ph+ve
      and Ph-ve) collections. In conclusion these data indicate that, in a consistent
      proportion of chronic myeloid leukemia patients, intensive chemotherapy is able
      to recruit Ph-ve LTC-ICs in to the peripheral blood. Moreover these data provide
      the biological basis for developing autografting programs with Ph-negative cells.

PMID- 8528172
TI  - Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal
      progenitor cells (mesenchymal progenitor cells): implications for therapeutic
      use.
AB  - We report a phase I trial to determine the feasibility of collection, ex vivo
      culture-expansion and intravneous infusion of human bone marrow-derived
      progenitor stromal cells (mesenchymal progenitor cells (MPCs)). Ten milliliter
      bone marrow samples were obtained from 23 patients with hematologic malignancies
      in complete remission. Bone marrow mononuclear cells were separated and adherent
      cells were culture-expanded in vitro for 4-7 weeks. Autologous MPCs were
      reinfused intravenously and a bone marrow examination repeated 2 weeks later for
      histologic assessment and in vitro hematopoietic cultures. Patient age ranged
      from 18 to 68 years and 12 subjects previously had undergone an autologous or
      syngeneic bone marrow transplant 4-52 months prior to collection of MPCs. A
      median of 364 x 10(6) nucleated bone marrow cells (range: 103 to 1004 x 10(6))
      were used for ex vivo expansion. Median number of MPCs which were obtained after
      ex vivo culture expansion was 59.0 (range: 1.1 to 347 x 10(6)) representing a
      median cell doubling of 16,000-fold (13 doublings). Fifteen of 23 patients
      completed the ex vivo expansion and underwent MPC infusion. Time to infusion of
      MPCs after collection ranged from 28 to 49 days. Five patients in each of three
      groups were given 1, 10 and 50 x 10(6) MPCs. No adverse reactions were observed
      with the infusion of the MPCs. MPCs obtained from cancer patients can be
      collected, expanded in vitro and infused intravenously without toxicity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8528174
TI  - Cardiac and respiratory function after bone marrow transplantation in children
      with leukaemia.
AB  - Late cardiac and respiratory function changes were evaluated in children
      surviving disease-free more than 2 years after bone marrow transplantation (BMT)
      performed for haematological malignancies. Forty-one children received allogeneic
      and 10 autologous BMT. In all cases studied shortening fraction (SF) was always
      within normal limits from before BMT up to 4 years after BMT. SF, though still
      normal, was slightly lower in the group with higher pre-BMT cumulative
      anthracycline dose. Twenty-eight children underwent respiratory function tests
      regularly at all scheduled times (pre-BMT, +6 months, +1, +2, +3, +4 years after
      BMT). Vital capacity and total lung capacity showed a slight continuous decrease
      which was significant at 4 years after BMT (P = 0.015 and P = 0.003
      respectively). The decline of forced expiratory volume in 1 s observed 1 year
      after BMT (P = 0.002) was roughly maintained over time. However, no children
      complained of symptoms attributable to respiratory dysfunction, and all indices
      studied were always within normal limits in almost all patients. So far late
      cardiac and lung changes following BMT in children seem to be negligible.
      However, whether such abnormalities could further worsen and impair adult quality
      of life remains to be ascertained.

PMID- 8528173
TI  - Cytosine arabinoside as a major risk factor for Streptococcus viridans septicemia
      following bone marrow transplantation: a 5-year prospective study.
AB  - The incidence and clinical course of nosocomial septicemia with Streptococcus
      viridans was evaluated prospectively in 242 consecutive bone marrow transplant
      (BMT) recipients throughout their 15-213 days' (median 47) hospitalization,
      including 4-58 days (median 18) of neutropenia. Initial empiric therapy for
      febrile neutropenia consisted of mezlocillin, gentamicin and cefazolin;
      glycopeptide was excluded. S. viridans septicemia occurred in 23/209 (11%)
      subjects with underlying malignant disease, and only during neutropenia with
      concomitant mucositis: in 20 subjects (four with ampicillin-resistant strains),
      S. viridans septicemia occurred at onset of febrile neutropenia, 1-5 days (median
      4.5) post-BMT. All survived with an uncomplicated clinical course. Thus,
      glycopeptide seems unnecessary in the initial empiric antibiotic regimen. The
      other three subjects demonstrated S. viridans septicemia (two with ampicillin
      resistant strains) on day 11 post-BMT; two died. The major risk identified was
      cytosine arabinoside administration in the conditioning regimen (P < 0.01).

PMID- 8528175
TI  - Prophylaxis of graft-versus-host disease in identical sibling donor bone marrow
      transplant by anti-IL-2 receptor monoclonal antibody LO-Tact-1.
AB  - The efficacy of the rat monoclonal IgG2b antibody LO-Tact-1 specific for the
      human interleukin-2 (IL-2) receptor was evaluated for prophylaxis of graft-versus
      host disease (GVHD) in patients who received transplants of marrow from HLA
      matched sibling donors. Fifteen patients received cyclosporine (CsA) + antibody
      LO-Tact-1, 0.2 mg/kg/day from day +7 to day +28. Twelve additional patients were
      administered methotrexate (MTX) + CsA+antibody LO-Tact-1, 0.4 mg/kg/day from day 
      1 to day +28. The antibody was well tolerated. Engraftment was not affected. GVHD
      grade > or = II occurred in six of 15 and eight of 12 patients receiving CsA+LO
      Tact-1 and MTX+CsA+LO-Tact-1, respectively (P = 0.52). GVHD grade > or = II
      developed in patients at a median of 32 and 34 days with CsA+LO-Tact-1 and
      MTX+CsA+LO-Tact-1, respectively (log-rank test, P = 0.57). GVHD contributed to
      death in four patients who were administered CsA+LO-Tact-1 and in one patient who
      was administered MTX+CsA+LO-Tact-1. Chronic GVHD occurred in two patients who
      were treated with CsA+LO-Tact-1 and in two patients treated with MTX+CsA+LO-Tact
      1. Throughout therapy, serum levels of LO-Tact-1 ranged from 2 to 10 mg/l. There
      was no correlation between serum levels of LO-Tact-1 and the occurrence of GVHD.
      GVHD occurred in 10 patients during LO-Tact-1 prophylaxis. There was no
      significant difference between relapse or survival rates among the patient
      groups. We conclude that, while free of adverse effects, monoclonal anti-IL-2
      receptor antibody LO-Tact-1 does not improve prophylaxis of GVHD in HLA-matched
      sibling BMT.

PMID- 8528176
TI  - Autoantibodies against 70-kDa heat shock proteins (HSP70) in allogeneic bone
      marrow transplant recipients.
AB  - We report that autoantibodies against the 70-kDa heat shock protein family
      (HSP70) were detected in allogeneic bone marrow transplant recipients. Antibodies
      to HSP70 family proteins were detected in three out of 14 recipients of an
      allogeneic marrow graft but in none of the seven patients receiving autologous
      peripheral blood stem cell transplant (PBSCT). Immunoblotting analysis combined
      with two-dimensional SDS-PAGE revealed that these patients had antibodies to a
      constitutive 73-kDa/pI 5.5 heat shock protein (HSP73) and to a stress-inducible
      72-kDa/pI 5.6 protein (HSP72). This is the first report, to our knowledge,
      describing the presence of autoantibody against HSP73 in allogeneic marrow
      transplant recipients. Our results may provide additional insight into the
      etiology and the pathophysiology of allogeneic transplant-related disorders.

PMID- 8528177
TI  - Intestinal mucosal mononuclear cell chimaerism after sex-mismatched allogeneic
      bone marrow transplantation.
AB  - The contribution of haemopoietic cell chimaerism to the pathogenesis of GVHD
      after BMT is unclear. This report raises the possibility that donor lymphocyte
      recipient macrophage chimaerism may occur shortly after allogeneic marrow
      engraftment and hence might contribute to the development of GVHD.
      Immunohistological studies of intestinal mucosa in an allogeneic BMT patient, who
      did not engraft, revealed an almost complete absence of lymphocytes 30 days after
      transplant, but preservation of mucosal macrophage numbers. Subsequently,
      combined immunohistology-Y chromosome in situ hybridization studies were
      performed in two female BMT recipients of male donor marrow. These studies
      revealed that between 25 and 40% of macrophages and between 25 and 40% of T
      lymphocytes were of donor origin during the first 6 months after transplant. In
      conclusion, whilst the immunohistological studies of intestinal mucosa from a
      patient who failed to engraft suggest that donor lymphocyte-recipient macrophage
      ('split') chimaerism may occur shortly after marrow engraftment, the subsequent
      in situ hybridization studies revealed 'mixed' chimaerism in the two sex
      mismatched BMT recipients.

PMID- 8528178
TI  - bcr/abl chimeric transcript in patients in remission after marrow transplantation
      for chronic myeloid leukemia: higher frequency of detection and slower clearance
      in patients grafted in advanced disease as compared to patients grafted in
      chronic phase.
AB  - The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as
      a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid
      leukemia (CML) subjected to allogeneic BMT and in complete hematological
      remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in
      advanced phase (AD), including 16 in accelerated phase and four in blastic
      transformation. A total of 135 samples collected between 4 and 105 months from
      BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20
      patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients
      analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of
      the residual disease at the molecular level in individual patients was recorded.
      The results have been correlated with a number of clinical parameters obtained
      before and after BMT; among the tested variables only the phase of the disease at
      BMT was associated with higher frequency of PCR positivity after BMT. The
      probability of finding persisting disease 1 year beyond BMT was significantly
      higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to
      patients grafted in CP (7/62, 11%). At any interval from BMT the difference
      between the two groups remained statistically significant: the bcr/abl transcript
      was present in 5/31 patients transplanted in CP compared to 9/15 patients
      transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP
      vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8528179
TI  - An MHC-compatible allogeneic bone marrow donor with a distinct role of T cell
      subsets in graft-versus-leukemia effect and lethal graft-versus-host disease.
AB  - Our previous results in a murine model indicated that the GVL effect against
      radiation-induced leukemias could be induced in not only MHC-incompatible but
      also MHC-compatible allogeneic BMT, and that the intensity of the GVL effect
      induced in MHC-compatible allogeneic BMT varied among different leukemias and the
      donor/host strain combinations used. With the use of a radiation-induced T cell
      leukemia which followed the induction of the GVL effect in both MHC-compatible
      and -incompatible, allogeneic BMT, the role of T cell subsets in the development
      of the GVL effect and GVHD was studied. The results indicated that Lyt2+ T cells
      contaminating donor BM were consistently critical for the induction of the GVL
      effect in MHC-incompatible (B10) and -compatible (B10.BR and AKR) allogeneic BMT
      of leukemia-bearing C3H mice, but the depletion of L3T4+ T cells had no effect.
      In contrast, lethal GVHD induced by AKR donor lymph node cells was totally
      dependent on L3T4+ T cells, but the depletion of Lyt2+ T cells had no effect. On
      the other hand, both T cell subsets could cause lethal GVHD induced by MHC
      incompatible (B10) and -compatible (B10.BR) allogeneic donors. The distinct roles
      of T cell subsets of AKR donors were confirmed by the preferential induction of
      the GVL effect with the AKR donor bone marrow mixed with lymph node cells which
      had been depleted of L3T4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528180
TI  - Extent of variability inherent in measurements of CD34-positive cells in
      different human haemopoietic tissues.
AB  - Estimation of CD34 expression is widely used to detect and quantify progenitor
      cells in haemopoietic tissues used as stem cell sources for transplantation.
      Mouse monoclonal antibodies to CD34 recognise different epitopes of the mucin
      like sialoglycoprotein. These epitopes can be grouped into three classes by their
      differing sensitivities to the enzymes: neuraminidase, chymopapain and
      glycoprotease. We have compared the expression, by flow cytometry, of the three
      CD34 epitopes on normal adult and fetal haemopoietic tissue and in chronic
      myeloid leukaemia, and have used four antibodies from each class to assess
      variability of staining within and between epitope classes. The results reveal
      variable expression of CD34 both within and between tissue types and antibody
      classes. As a result of the different levels of detection by different
      antibodies, the apparent number of CD34-positive cells vary by approximately 6
      fold. Enrichment for CD34 cells using magnetic bead technology shows a
      significant difference in the percentage of CD34 cells detected for two of the
      epitope types.

PMID- 8528181
TI  - Successful treatment of Curvularia sp infection in a patient with primarily
      resistant acute promyelocytic leukemia.
AB  - We report a young woman with acute promyelocytic leukemia who showed primary
      resistance to chemotherapy and who responded to ATRA treatment. During the
      neutropenic period she developed Curvularia sp infection and was finally
      successfully consolidated with autologous bone marrow transplantation.

PMID- 8528182
TI  - Successful allogeneic bone marrow transplantation in a case with myelodysplastic
      syndrome which developed following Fanconi anemia.
AB  - We report the case of a 14-year-old boy with myelodysplastic syndrome (MDS/RAEB)
      which developed following Fanconi anemia. The patient received BMT from an HLA
      identical sister. Based on the in vitro CY-sensitivity test, 100 mg/kg of CY was
      administered for conditioning combined with 6 Gy TBI. Mucosal symptoms such as
      stomatitis, diarrhea and hematuria were severe, but manageable, and engraftment
      was successful. The patient has maintained normal trilineage hematopoiesis with >
      90% Karnofsky score for 30 months with disappearance of a clonal chromosomal
      abnormality (47,XY, +i(lq)) which was detected before BMT.

PMID- 8528183
TI  - Allogeneic BMT from a donor with fragile X syndrome: cytogenetic and molecular
      evaluation.
AB  - We report the first case of engraftment of bone marrow collected from a donor
      with Fragile X syndrome with subsequent cytogenetic and molecular evaluation.
      Engraftment was prompt and stable. Whilst the Fragile X abnormality could be
      detected initially by molecular techniques in the peripheral blood, it could not
      be detected cytogenetically while the patient was receiving CsA.

PMID- 8528184
TI  - Rapid engraftment of peripheral blood progenitor cell grafts purged with B cell
      specific monoclonal antibodies and immunomagnetic beads.
AB  - PBPC harvesting was performed in two patients with advanced-stage low-grade non
      Hodgkin's lymphoma after mobilization with dexa-BEAM chemotherapy plus G-CSF. The
      collected grafts were subjected to immunomagnetic purging using B cell-specific
      moAbs and paramagnetic beads. Immunophenotypic and/or molecular analysis of the
      resulting products (PCR amplification of t(14;18) or CDR-III rearrangements)
      demonstrated successful depletion of lymphoma cells. Rapid and durable
      hematopoietic recovery occurred after reinfusion of the purged grafts following
      myeloablative radiochemotherapy (9-10 days to neutrophils > 0.5 x 10(9)/l; 9-11
      days to platelets > 20 x 10(9)/l). We conclude that effective immunomagnetic
      purging of PBPC grafts is feasible without affecting engraftment.

PMID- 8528185
TI  - Does the type of delivery influence umbilical cord blood recovery?

PMID- 8528186
TI  - Anti-D antibody of exclusive IgM class after minor Rh(D)-mismatched BMT.

PMID- 8528187
TI  - The use of non-cryopreserved peripheral blood progenitor cells in autologous
      transplantation.

PMID- 8528188
TI  - Therapy of cyclophosphamide-induced nasal congestion.

PMID- 8528189
TI  - Distribution of fibronectin in foetal tissues.
AB  - The distribution of fibronectin in tissues of four human foetuses (7-14 gestation
      weeks/GW) and twenty seven pig foetuses (25-114 days of gestation) was
      investigated using immunofluorescence and avidin/biotin methods. Fibronectin was
      abundant in the circulatory and gastrointestinal system and its derivates, in
      reticular stroma of immune organs, and in connective tissues and chorionic villi
      at all developmental stages.

PMID- 8528190
TI  - Polyamines and terminal deoxynucleotidyl transferase expression in KM 3 pre-B
      cell line during phorbol ester induced differentiation.
AB  - The aliphatic polyamines, putrescine, spermine and spermidine belong to a
      category of molecules implicated in DNA replication. Their synthesis is strongly
      activated during the G1 period and they have been implicated in the regulation of
      cell proliferation and differentiation. Terminal transferase is a DNA polymerase
      present in pre-T and pre-B cells and its expression can be modulated by phorbol
      ester treatment. In this study we have monitored the relationship of
      intracellular polyamine levels with terminal deoxynucleotidyl transferase down
      regulation induced by 12-O-tetradecanoyl phorbol myristate 13-acetate treatment
      in the human pre-B KM-3 cell line. Phorbol myristate acetate can cause an
      increase, at 4 and 8 hours of differentiation, of intracellular levels of
      putrescine as well as a decrease in terminal deoxynucleotidyl transferase
      synthesis showing the probable involvement that polyamines have in the
      differentiation process.

PMID- 8528191
TI  - Digital image analysis of chromatin fibre phenotype after "in situ" digestion
      with restriction endonucleases.
AB  - Restriction Endonucleases (REs) may recognize, cleave and remove DNA from fixed
      chromatin producing specific chromosome banding patterns. However, the
      modifications produced in the chromatin fibre are not easy to evaluate and
      compare. The aim of the present investigation was to visualize differences
      resulting in the texture of the chromatin fibre from metaphase chromosomes after
      each digestion using digital image analysis (DIA) facilities. To this purpose,
      metaphase chromosomes derived from a L-929 mouse cell line were digested with
      different REs (AluI, HpaII and HaeIII). Since light microscopy does not permit
      the observation of the chromatin fibre, DIA was performed on digitalized images
      of metaphase chromosomes under electron microscopy. The application of a LUT
      (Look Up Table) within the DIA software assigns a colour to each grey level of a
      digital image. The results obtained using a particular LUT, which permits the
      discrimination of specific chromatin fibre phenotypes resulting from each
      digestion, are reported and compared with those obtained under the light
      microscope.

PMID- 8528192
TI  - Secretion of TNF-alpha from macrophages following induction with a lignin
      derivative.
AB  - Macrophages derived from rat bone marrow were treated with macrophage colony
      stimulating factor (M-CSF) to obtain a sufficient number of cells for the tumor
      necrosis factor (TNF-alpha) assay. The present study has been designed to
      investigate whether the production of TNF-alpha, which induces multinucleated
      giant cell formation, is regulated by polyanions such as lignin derivatives.
      ELISA for TNF-alpha showed that the polyanion induced TNF-alpha production by
      macrophages. The secretion of TNF-alpha from the cells reached a maximum at 3-6
      h, and then showed a slight decline. Northern blotting of TNF-alpha mRNA showed
      that the amount of TNF-alpha reached a maximum within 1 h of macrophage culture
      in the presence of a lignin derivative. On the other hand, TNF-alpha mRNA was
      undetectable in the control cells. It was concluded that stimuli such as that
      provided by lignin derivatives increases the amount of TNF-alpha mRNA, which is
      then followed by translation of TNF-alpha.

PMID- 8528193
TI  - Effect of extracellular matrix proteins on vascular smooth muscle cell phenotype.
AB  - The effect on phenotypic expression of rabbit vascular smooth muscle cells (SMC)
      of the interstitial matrix proteins collagen I and fibronectin, the basal lamina
      proteins collagen IV and laminin, and the serum adhesion protein vitronectin was
      examined in culture. Experiments were performed in foetal calf serum stripped of
      fibronectin and vitronectin to eliminate their confounding effects. All the
      proteins promoted adhesion to the plastic culture dish (in a concentration
      dependent manner) of SMC freshly isolated from the artery wall. These cells had a
      high volume density of myofilaments (Vvmyo) in their cytoplasm. Laminin was best
      at maintaining SMC with a high Vvmyo (Vvmyo = 49.8%) followed by collagen IV
      (41.7%). Cells plated on vitronectin showed the lowest Vvmyo (31.3%). The results
      support the concept that the SMC basal lamina has a role in maintaining cells in
      the high Vvmyo phenotype.

PMID- 8528194
TI  - Differences in the motility of Amoeba proteus isolated fragments are determined
      by F-actin arrangement and cell nucleus presence.
AB  - Isolated fragments produced by bisection of Amoeba proteus differ by their
      position in the original cell and by the presence or absence of the cell nucleus.
      Immediately after the operation, both types of anterior fragments preserve the
      former motory polarity, and do not interrupt locomotion. In the same time, all
      posterior fragments stop, round up and fail to react stimuli. In the second phase
      of experiment, these anterior fragments, which had no nucleus ceased to move,
      whereas the nucleated posterior ones resumed locomotion. It was demonstrated,
      that the behaviour of a fragment is primarily determined by the peripheral F
      actin distribution, which is different depending on the origin of the fragment
      either from the anterior or from the posterior cell region. Later, the
      "inherited" F-actin distribution may be stabilized or reorganized in the presence
      of the nucleus, or desorganized in its absence.

PMID- 8528195
TI  - Maintenance of cytochrome P-450 levels in hepatocytes preserved on gelatin gels.
AB  - In culture, cytochrome P-450 levels fall rapidly with the result that hepatocytes
      are either used quickly or maintained in modified systems which prejudice their
      subsequent behaviour. In this study the effect of hypothermic preservation of
      hepatocytes on gelatin gels on levels of cytochrome P-450 was investigated. In
      marked contrast to conventional cultures, hypothermic preservation (10 degrees)
      maintained, over a 6-day period, cytochrome P-450 at levels similar to those of
      the more stable cytochrome b5. Cell storage on gelatin at 25 degrees was
      associated with a conversion of cytochrome P-450 to cytochrome P-420. The
      procedure at 10 degrees provides a valuable tool for toxicity testing, hepatocyte
      conservation and distribution.

PMID- 8528196
TI  - The cell and the organism: the role of subdivisional cell replication in the
      development and maintenance of the multicellular organism.
AB  - Evidence of new cell formation from nucleoli (subdivisional cell replication) was
      observed in vitro and in vivo. Mouse melanoma cells, human fibroblasts, and rat
      mast cells were observed in tissue culture with phase contrast time-lapse
      cinematography. Evidence of subdivisional cell replication seen in tissue culture
      was supported by observations of mast cells, cervical epithelial cells, melanoma
      cells, keratinocytes, and fungal spores in vivo. Indirect evidence for
      subdivisional cell replication was the presence of differentiated form and
      function in nuclei and nucleoli. Synergism between subdivisional replication and
      mitotic replication (subdivisional expansion) is believed to be a key to
      morphogenesis, whereby cellular and subdivisional zones act as biologic "molds".
      It is believed that subdivisional cell replication has a key role in maintenance
      of differentiated form in multicellular organisms, as well as in morphogenesis.

PMID- 8528197
TI  - Influence of acetaldehyde and ethanol on rat hepatic lipocyte characteristics in
      primary culture.

PMID- 8528198
TI  - Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and
      isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.
AB  - Mutation in the gene encoding the recently isolated WASP protein has now been
      identified as the genetic defect responsible for the X-linked Wiskott-Aldrich
      syndrome (WAS), a primary immunodeficiency disease associated with extensive
      phenotypic variability. To elucidate the range of WASP mutations responsible for
      WAS, we used PCR-SSCP analysis to screen for WASP gene mutation in 19 unrelated
      boys with the diagnosis of classical or attenuated WAS or isolated
      thrombocytopenia. All 19 patients had WASP mutations, each of which localized to
      the initial three or terminal three exons of the gene, and the majority of which
      were unique in each case. However, a missense mutation which results in
      substitution of the arginine at WAS codon 86 was identified in three boys with
      severe WAS as well as in one boy presenting with thrombocytopenia alone. While
      the three mutations found in the isolated thrombocytopenia patients leave the
      reading frame intact, about one-half of the gene alterations detected in both
      severe and attenuated WAS patients result in frameshifted transcript and
      premature translation termination. These findings therefore confirm the
      association of WAS with WASP mutation and identify WASP mutation as a cause for
      isolated congenital thrombocytopenia in males. While the WASP gene defects
      responsible for isolated thrombocytopenia and other mild presentations of WAS do
      not appear distinct from those resulting in severe WAS, these data indicate that
      analysis of WASP gene mutation provides a valuable tool for distinguishing the
      spectrum of WAS patients and the subset of males with isolated thrombocytopenia
      who represent mild cases of WAS.

PMID- 8528199
TI  - WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.
AB  - The WASP gene has been recently cloned from Xp11.23 and shown to be mutated in
      three patients with the Wiskott-Aldrich syndrome (WAS). We have developed a
      screening protocol for identifying WASP gene alterations in genomic DNA and have
      identified a spectrum of novel mutations in 12 additional unrelated families.
      These missense, nonsense and frameshift mutations involve eight of the 12 exons
      of the gene. Two mutations creating premature termination codons were associated
      with lack of detectable mRNA on Northern blots. Four amino acid substitutions,
      Leu27Phe, Thr48Ile, Val75Met and Arg477Lys, were found in patients with
      congenital thrombocytopenia and no clinically evident immune defect indicating
      that the WASP gene is the site for mutations in X-linked thrombocytopenia as well
      as in WAS. A T-cell line from a WAS patient contained two independent DNA
      alterations, a constitutional frameshift mutation, also present in peripheral
      blood leukocytes from the patient, and compensatory splice site mutation unique
      to the cell line. The distribution of eight missense mutations provides valuable
      information on amino acids which are essential for normal protein function, and
      suggests that sites in the first two exons are hot-spots for mutation.

PMID- 8528200
TI  - Evidence for inter-generational instability in the CAG repeat in the MJD1 gene
      and for conserved haplotypes at flanking markers amongst Japanese and Caucasian
      subjects with Machado-Joseph disease.
AB  - The size of the (CAG)n repeat array in the 3' end of the MJD1 gene and the
      haplotype at a series of microsatellite markers surrounding the MJD1 gene were
      examined in a large cohort of Japanese and Caucasian subjects affected with
      Machado-Joseph disease (MJD). Our data provide five novel observations. First,
      MJD is associated with expansion fo the array from the normal range of 14-37
      repeats to 68-84 repeats in most Japanese and Caucasian subjects, but no subjects
      were observed with expansions intermediate in size between those of the normal
      and MJD affected groups. Second, the expanded allele associated with MJD displays
      inter-generational instability, particularly in male meioses, and this
      instability was associated with the clinical phenomenon of anticipation. Third,
      the size of the expanded allele is not only inversely correlated with the age-of
      onset of MJD (r = -0.738, p < 0.001), but is also correlated with the frequency
      of other clinical features [e.g. pseudoexophthalmos and pyramidal signs were more
      frequent in subjects with large repeats (p < 0.001 and p < 0.05 respectively)].
      Fourth, the disease phenotype is significantly more severe and had an early age
      of onset (16 years) in a subject homozygous for the expanded allele, which
      contrasts with Huntington disease and suggests that the expanded allele in the
      MJD1 gene could exert its effect either by a dominant negative effect (putatively
      excluded in HD) or by a gain of function effect as proposed for HD. Finally,
      Japanese and Caucasian subjects affected with MJD share haplotypes at several
      markers surrounding the MJD1 gene, which are uncommon in the normal Japanese and
      Caucasian population, and which suggests the existence either of common founders
      in these populations or of chromosomes susceptible to pathologic expansion of the
      CAG repeat in the MJD1 gene.

PMID- 8528201
TI  - Heterogeneity of DM kinase repeat expansion in different fetal tissues and
      further expansion during cell proliferation in vitro: evidence for a casual
      involvement of methyl-directed DNA mismatch repair in triplet repeat stability.
AB  - We have analysed the mitotic behaviour of expanded CTG repeats in somatic tissues
      and cultured somatic cells from myotonic dystrophy (DM) fetuses using indirect
      and direct methods. Heterogeneity of expansions between fetal tissues was
      demonstrated in a 16 week old fetus whereas there was no evidence for such a
      somatic heterogeneity in a 13 week old fetus. Dilution plating of cultured cells
      from an adult patient and a fetus resulted in isolation of clones showing single
      expanded restriction fragments when the donor showed a heterogeneous smear of
      expansions or a single expanded fragment. During proliferation in vitro to 45
      doublings, DM cells experienced highly synchronous further repeat expansion which
      first became evident at approximately 15 cell generations and reached a plateau
      of maximum expansion at approximately 200 days. When mathematically expressed as
      a function of culture time the dynamics of expansion of restriction fragments
      followed a sigmoid curve. This unstable behaviour of CTG repeat expansions in DM
      was compared to the mitotically stable patterns of full mutation in fragile X
      fetal tissues and led to the hypothesis that methylation of CpGs within the
      repeat sequence is a stabilizing factor of largely expanded CGG and GCC repeats
      allowing for efficient methyl-directed strand-specific DNA mismatch repair.

PMID- 8528202
TI  - A yeast assay for functional detection of mutations in the human cystathionine
      beta-synthase gene.
AB  - Mutations in the human cystathionine beta-synthase (CBS) gene are known to cause
      homocystinuria and may also be a significant risk factor for premature
      atherosclerosis. We have previously shown that the human CBS protein can
      substitute for the endogenous yeast CBS protein in Saccharomyces cerevisiae. We
      now show that expression of three different CBS mutants known to be associated
      with reduced enzyme activity in humans fail to complement growth in the yeast
      assay. In addition, we have used the yeast CBS assay to identify eight mutant CBS
      alleles in cell lines from patients with CBS deficiency. These mutant alleles
      include two previously identified and five novel CBS mutations. Our results also
      demonstrate that the yeast CBS assay can detect a large percentage of individuals
      heterozygous for mutations in CBS. This system should be useful in determining
      the relationship between CBS mutations and human disease.

PMID- 8528203
TI  - A common missense mutation in the adhalin gene in three unrelated Brazilian
      families with a relatively mild form of autosomal recessive limb-girdle muscular
      dystrophy.
AB  - Autosomal recessive limb-girdle muscular dystrophies (AR LGMD) represent a
      heterogeneous group of diseases with a wide spectrum of clinical variability,
      classified phenotypically into two main groups, the most severe forms (Duchenne
      like muscular dystrophy, DLMD, or severe childhood autosomal recessive muscular
      dystrophy, SCARMD) and the milder forms. Four genes causing AR LGMD have been
      mapped: the 15q (LGMD2a), the 2p (LGMD2b), the 13q locus (LGMD2c) and the adhalin
      gene on chromosome 17q (LGMD2d). In the present report we have performed linkage
      analysis with 17q markers in three mild AR LGMD and in four DLMD families with
      adhalin deficiency and unlinked to 2p, 15q or 13q genes. Linkage was observed
      only among the mild cases. Patients from these three 17q-linked families showed
      near or total deficiency of adhalin in muscle biopsies. An identical missense
      mutation was identified in all three 17q-linked unrelated families. These results
      indicate that AR LGMD with a mild phenotype is caused by mutations in the adhalin
      gene. In addition, they demonstrate that there is at least one other locus for
      DLMD associated with adhalin deficiency.

PMID- 8528204
TI  - Double mutant alleles: are they rare?
AB  - The presence of two different mutations carried by the same CF allele has been
      demonstrated in four out of 44 Bulgarian CF patients during a systematic search
      of the entire coding sequence of the CFTR gene. Two of the double mutant alleles
      include one nonsense and one missense mutation and although the nonsense mutation
      can be considered to be the main defect, the amino acid substitutions are good
      candidates for disease-causing mutations as well. One double mutant carries two
      missense mutations whose contribution to the CF phenotype is difficult to
      evaluate. The findings suggest that double mutant alleles may be more common than
      expected and could account for some of the problems in phenotype-genotype
      correlations. Such alleles may have important implications for molecular
      diagnosis and genetic counselling.

PMID- 8528205
TI  - Expression of the Huntington disease gene in rodents: cloning the rat homologue
      and evidence for downregulation in non-neuronal tissues during development.
AB  - Huntington's disease (HD) is associated with an expanded and unstable (CAG) > 35
      repeat within a gene of unknown function. We isolated the complete coding region
      of the rat HD gene (rhd) from cDNA libraries and investigated its expression in
      different developmental stages of rodent tissues. The rat gene exhibits 90%
      peptide sequence identity to the human and 96% to the murine sequence. The (CAG)n
      repeat is markedly reduced in the rat compared to the average human (CAG)n block.
      Northern blot analysis and in situ hybridizations reveal that in rodents the hd
      gene is already expressed during embryonal development. As in humans, the rhd
      gene is expressed in two transcriptional isoforms which result from different
      polyadenylation signals. In mice, however, a third transcript of intermediate
      size was found predominantly expressed in brain. This transcript is downregulated
      in later development. At day 14.5 p.c. the level of rhd expression is similar in
      the brain and in non-neuronal tissues. In contrast, the expression in non
      neuronal tissues is markedly reduced in adult animals and corresponds to the
      restricted distribution of neuropathologic changes observed in HD patients.

PMID- 8528206
TI  - Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for
      bilirubin UDP-glucuronosyltransferase.
AB  - Gilbert's syndrome, which is characterized by chronic, non-hemolytic unconjugated
      hyperbilirubinemia, is caused by a reduction in the activity of hepatic bilirubin
      UDP-glucuronosyltransferase (UGT). Here, we report that all examined patients
      with this disease carried missense mutations in the gene for UGT and that the
      mutations were heterozygous. An expression study in COS cells in vitro, using the
      expression vector pcDL that carried the mutated gene for UGT from a patient,
      indicated that approximately 14% of the normal UGT activity was expressed.
      However, the UGT activity of the patient with Gilbert's syndrome was unexpectedly
      < 50% of the normal, perhaps as the result of the dominant negative nature of the
      mutation.

PMID- 8528207
TI  - A novel mutation causing an aberrant splicing in the protein 4.2 gene associated
      with hereditary spherocytosis (protein 4.2Notame).
AB  - We investigated a Japanese patient with protein 4.2 deficiency. SDS-PAGE showed a
      complete deficiency of protein 4.2, while Western blot analysis revealed a marked
      decrease in the amount of protein 4.2, and the existence of a doublet of 74 and
      72 kDa bands. Direct sequencing and dot-blot hybridization with allele-specific
      oligonucleotide probes indicated that the proband was compound heterozygous for a
      missense mutation in codon 142 with Ala-->Thr (GCT-->ACT) and a single nucleotide
      substitution (G-->A) of the first base of intron 6 (G-->A) of the protein 4.2
      gene. The former is the commonest mutation observed in cases of protein 4.2
      deficiency, whereas the latter is a novel mutation, located within the consensus
      sequence of the 5' splicing site (AGGU) (Protein 4.2Notame). RT-PCR analysis
      using total RNA isolated from reticulocytes of the proband revealed that the
      intron 6 donor site mutation causes an abnormal splicing; exon 6 is spliced out
      with intron 6. The abnormal mRNA has a premature termination codon, as the result
      of a frameshift, and this instability may lead to degradation. Thus, there is a
      close relation between this mutation and the molecular pathogenesis of protein
      4.2 deficiency.

PMID- 8528208
TI  - The tetranucleotide repeat polymorphism D21S1245 demonstrates hypermutability in
      germline and somatic cells.
AB  - Six novel polymorphic short sequence repeats were identified and localized on the
      linkage map of human chromosome 21 by genotyping the CEPH reference pedigrees.
      One of these markers, the tetrameric (AAAG)n repeat D21S1245, was found to be
      hypermutable. In the DNAs from lymphoblastoid cell lines of members of the 40
      CEPH families a total of 18 new alleles were detected. These new alleles,
      sometimes appearing in mosaic forms, arose equally in paternal and maternal DNAs,
      and could be equally larger or smaller than the alleles from which they were
      derived. The larger alleles of D21S1245 are more prone to be converted to new
      alleles. None of the new alleles with mosaicism were present in the corresponding
      genomic blood DNA, and therefore originated during or after the establishment of
      the lymphoblastoid cell lines; half of the new alleles without mosaicism were
      also found in genomic blood DNA of the appropriate CEPH individuals. The range of
      germline mutation rate observed in the 716 meioses examined was 0.56-1.4 x 10(
      2); the range of somatic mutations observed in the 405 cell lines examined was
      1.96-3.46 x 10(-2). This is one of the most hypermutable microsatellite repeat
      polymorphism in the human genome detected to date. D21S1245, is highly
      polymorphic (heterozygosity of 0.96) and maps between D21S231 and D21S198.

PMID- 8528209
TI  - Mapping of genes predisposing to idiopathic generalized epilepsy.
AB  - Idiopathic generalized epilepsy (IGE) is characterized by recurring generalized
      seizures in the absence of detectable brain lesions and/or metabolic
      abnormalities. Twin and family studies suggest that genetic factors play a key
      part in IGE. A multilocus model appears to best fit the observed inheritance
      patterns. Mapping of IGE-related genes has been previously attempted using
      parametric methods, with conflicting results. In particular, recent evidence
      argues both for and against a chromosome 6p locus (EJM1) for juvenile myoclonic
      epilepsy, a subtype of IGE. We have approached the problem of mapping IGE loci
      using non-parametric methods, which have recently been successful for other
      complex diseases. No evidence for linkage to chromosome 6p was obtained. However,
      we obtained evidence for involvement of a locus at chromosome 8q24, close to the
      marker D8S256. The same 8q24 region was previously implicated in families with
      benign neonatal familial convulsions (BNFC), a generalized epilepsy syndrome that
      is inherited as a simple dominant mendelian trait. There is an apparent conserved
      syntenic group of genes in human 8q24 and a region of mouse chromosome 15, which
      harbors the stargazer (stg) locus. Homozygous mutant mice at the stg locus show a
      form of generalized epilepsy that resembles human absence epilepsy. Our findings
      may have implications for a locus on 8q24 predisposing to IGE.

PMID- 8528210
TI  - Recessively inherited L-DOPA-responsive dystonia caused by a point mutation
      (Q381K) in the tyrosine hydroxylase gene.
AB  - Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L
      dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of
      dopamine. Recently, we described a point mutation in hTH (Q381K) in a family of
      two siblings suffering from progressive L-DOPA-responsive dystonia (DRD),
      representing the first reported mutation in this gene. We here describe the
      cloning, expression and steady-state kinetic properties of the recombinant mutant
      enzyme. When expressed by a coupled in vitro transcription-translation system and
      in E. coli, the mutant enzyme represents a kinetic variant form, with a reduced
      affinity for L-tyrosine. The 'residual activity' of about 15% of the
      corresponding wild-type hTH (isoform hTH1), at substrate concentrations
      prevailing in vivo, is compatible with the clinical phenotype of the two Q381K
      homozygote patients carrying this recessively inherited mutation.

PMID- 8528211
TI  - A gene for a severe lethal form of X-linked arthrogryposis (X-linked infantile
      spinal muscular atrophy) maps to human chromosome Xp11.3-q11.2.
AB  - X-linked arthrogryposis Type I (X-linked infantile spinal muscular atrophy) is a
      rare disorder showing hypotonia, areflexia, and multiple congenital contractures
      (arthrogryposis) associated with loss of anterior horn cells and death in
      infancy. We have studied an X-linked arthrogryposis family using highly
      polymorphic microsatellite markers throughout the X chromosome. Meiotic
      breakpoint analysis (concordance analysis) based on shared regions of the founder
      X chromosome was successful in localizing the X-linked arthrogryposis gene to
      Xp11.3-q11.2. In this region, the highest two-point lod score was found with
      DXS991 (Zmax = 2.63, theta = 0.00). In multipoint linkage analysis covering the
      entire X chromosome, only the region defined by MAOB and DXS991 showed positive
      lod scores and all other regions showed negative lod scores. These data establish
      the first gene mapping assignment of an X-linked lethal form of human lower motor
      neuron disease.

PMID- 8528212
TI  - Investigation of the factor VIII intron 22 repeated region (int22h) and the
      associated inversion junctions.
AB  - A region of intron 22 of the factor VIII gene, which contains factor VIII
      associated gene A (F8A), is repeated twice more nearer the Xq telomere. It has
      been proposed that intrachromosomal homologous recombination occurs between the
      intron 22 repeat and either of the two extragenic copies, resulting in the
      recurrent inversions that cause almost half of all cases of severe haemophilia A.
      We have precisely defined the repeated region as 9.5 kb of DNA which we have
      termed int22h (intron 22 homologous region). The junctions of the inversions
      examined were shown to represent precise exchanges between the int22h repeats,
      thus providing conclusive evidence for homologous recombination. The three copies
      of int22h were compared along 8 kb of their length, using chemical mismatch
      analysis, and found to be 99.9% similar. The presence of such long, almost
      identical inverted repeats near the Xq telomere could account for the high
      frequency at which the inversions occur.

PMID- 8528213
TI  - Localisation of a gene for chondrocalcinosis to chromosome 5p.
AB  - Chondrocalcinosis is a common disorder which may associate with acute and chronic
      arthritis. A familial form, inherited as an autosomal dominant trait, has been
      mapped in a large family in which affected members also suffer recurrent fits in
      childhood. The gene which causes this disease shows linkage with several
      polymorphic markers on chromosome 5p with a maximum multipoint lod score of 4.6
      between D5S810 and D5S416. Mapping a locus for chondrocalcinosis will allow the
      heterogeneity of the disorder to be assessed and may also be relevant to
      understanding the aetiology of osteoarthritis with which it commonly associates.

PMID- 8528215
TI  - The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene
      causes a truncated transcript in cross-reacting material negative patients.

PMID- 8528214
TI  - Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic
      heterogeneity and phenotypic variability.
AB  - Mutations have been reported for several craniosynostotic disorders in exon IIIa
      (exon U or 7) or IIIc (exon B or 9) of the fibroblast growth factor receptor 2
      gene (FGFR2). Among the conditions with FGFR2 mutations are two autosomal
      dominant syndromes, Crouzon and Jackson-Weiss. In this study, 24 Crouzon and one
      Jackson-Weiss syndrome patients were screened for mutations in the two exons by
      direct sequencing, and mutations were detected in 28% (7/25) of all cases. Five
      different mutations were found including two novel (W290G, C342W) and two
      previously reported, recurrent mutations for Crouzon syndrome (A344A, S354C), and
      one new mutation for Jackson-Weiss syndrome (C342R). The W290G mutation was found
      in exon IIIa which is common to both alternatively spliced forms of FGFR2, BEK
      (expressed predominantly in primordial bones) and KGFR (expressed preferentially
      in epithelia). Atypical Crouzon syndrome features of epithelial-derived anal
      and/or external ear anomalies were present in the two affected family members
      with the mutation. This phenotype possibly reflects the expression of both mutant
      BEK and KGFR. In addition, the Jackson-Weiss syndrome mutation, C342R, in exon
      IIIc was observed previously in other craniosynostotic syndromes, Crouzon and
      Pfeiffer. These results underscore the allelic heterogeneity of these conditions
      and the complexity of the phenotypic consequences of FGFR2 mutations.

PMID- 8528216
TI  - Two novel mutations in the gene for copper zinc superoxide dismutase in UK
      families with amyotrophic lateral sclerosis.

PMID- 8528217
TI  - Structure--function relationships of anti-DNA antibodies.

PMID- 8528218
TI  - Research methods for investigating causal relations between SLE disease variables
      and psychiatric symptomatology.
AB  - People with systemic lupus erythematosus (SLE) frequently experience psychiatric
      problems. Some researchers and clinicians presume that these psychiatric problems
      are a direct manifestation of the disease, while others suggest that psychosocial
      and environmental factors have greater etiological significance. The majority of
      the studies addressing these issues in patients with SLE are too methodologically
      limited to make confident conclusions regarding etiology. More methodologically
      sound research in this area is needed. This article describes some of the
      limitations in past research in the areas of sampling, measurement, research
      design, data analyses and data presentation. Suggestions for improved methodology
      in future research are offered.

PMID- 8528219
TI  - Mixed connective tissue disease: fact or fiction?

PMID- 8528220
TI  - Mixed connective tissue disease dispute.

PMID- 8528221
TI  - Acute reversible hypoxemia in systemic lupus erythematosus: a new syndrome or an
      index of disease activity?
AB  - In 1991, Abramson et al reported a new syndrome of acute reversible hypoxemia
      (ARH) in patients with severe SLE (systemic lupus erythematosus). This syndrome
      was characterized by an unexplained abnormal value of arterial blood gases (ABG)
      without obvious parenchymal lung disease, and a good response to high-dose
      corticosteroid therapy. After we became aware of this entity, four of 16 patients
      admitted to our unit because of a SLE flare presented respiratory symptoms and
      abnormal ABG consistent with ARH. In none of our patients were the pulmonary
      manifestations a prominent clinical feature of the disease. Furthermore, in two
      of them, treatment with high-dose aspirin and moderate to low doses of
      corticosteroids was sufficient to improve the pulmonary manifestations, but not
      to control the systemic activity of the disease. Therefore, we believe that this
      new pulmonary finding more than a clinically independent syndrome represents an
      index of disease activity in patients with SLE.

PMID- 8528222
TI  - Demonstration of antiphospholipid antibody heterogeneity by phospholipid column
      chromatography and salt gradient elution techniques.
AB  - Antiphospholipid (aPL) antibodies are associated with thrombosis, recurrent
      abortions and thrombocytopenia. Studies to determine the mechanisms of action of
      these antibodies have been hindered by their heterogeneity and limited
      availability of techniques to isolate and characterize subgroups of the
      antibodies. We report a new phospholipid affinity chromatography method which
      enables separation of antiphospholipid positive sera into more than one antibody
      subpopulation. Sera from five patients with complications of the antiphospholipid
      syndrome (APS) were studied. Each serum was applied to chromatography columns
      prepared by coating polystyrene beads (diameter 100 A) with phosphatidylserine
      (PS) or cardiolipin (CL). A linear salt gradient (0.03-1.0 M NaCl) was used for
      elution. Eluates were analyzed for phospholipid binding and for inhibition of the
      prothrombin-thrombin conversion reaction. Each sample yielded two to three peaks
      for CL and PS affinity columns. Molarities at which peaks were eluted differed
      between samples. For individual samples, molarities at which peaks were eluted
      differed between CL and PS columns. These data suggest that aPL antibodies are
      heterogenous, with differences existing between patients and even within single
      serum samples. Subpopulations differed in their avidities for CL and PS but
      generally all had prothrombinase inhibitory activity.

PMID- 8528223
TI  - Factors associated with mood and mood disorders in SLE.
AB  - This study examines the relative contribution of factors associated with anxious
      and depressed mood, and clinical anxiety and depression in SLE. Eighty
      sequentially consenting patients attending a rheumatology outpatient clinic were
      assessed on measures of anxiety and depression; disease activity; presence of
      autoantibodies; neuropsychological performance; and psychological and social
      factors. Mood and mood disorders were found to be unrelated to measures of
      disease activity but were found to be associated with psychological and social
      factors. These findings emphasise the importance of psychosocial factors in
      attempts to understand mood and psychological distress in SLE.

PMID- 8528224
TI  - Thyroid peroxidase autoantibodies and their effects on enzyme activity in
      patients with systemic lupus erythematosus.
AB  - Thyroid microsomal antibodies (Ms-Ab) are recently proved to be directed to
      thyroid peroxidase (TPO). The aim of this study was to investigate whether the
      sera of patients with systemic lupus erythematosus (SLE) contain anti-TPO
      antibodies (TPO-Ab) and whether these antibodies influence enzyme activity. Sera
      from patient with Hashimoto's thyroiditis was also studied. Serum samples were
      obtained from 37 patients with SLE, 20 patients with Hashimoto's thyroiditis and
      20 healthy subjects. TPO-Ab were detected by immunoprecipitation using crude
      microsomal preparations or enzyme-linked immunoabsorbent assay (ELISA) with
      recombinant TPO. Positive TPO-Ab by ELISA were found in 11 (61%) of 18 patients
      with lupus whose serum contained Ms-Ab. Low levels of TPO-Ab also were found in
      three (16%) of 19 lupus sera that did not contain Ms-Ab. All patients with
      Hashimoto's thyroiditis had high levels of TPO-Ab in serum. When measured by
      ELISA, TPO-Ab were highly correlated with the results of a TPO
      immunoprecipitation assay and with the titers of Ms-Ab in patients with lupus (r
      = 0.83, n = 18, P < 0.01; r = 0.63, n = 18, P < 0.01) and in Hashimoto's
      thyroiditis (r = 0.89, n = 20, P < 0.01; r = 0.75, n = 20, P < 0.01). When
      evaluating the direct influence of TPO-Ab on the activity of TPO, we found no
      significant inhibition of enzymatic activity in both guaiacol and iodide assays
      by lupus sera in contrast with sera from Hashimoto's thyroiditis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8528225
TI  - Modulation of disease activity in murine systemic lupus erythematosus by cytokine
      gene delivery.
AB  - Somatic gene therapy is a novel approach with the potential to achieve prolonged
      increases in circulating levels of peptide hormones and cytokines. The present
      study evaluates the effects of monthly, intramuscular injections of cDNA
      expression vectors encoding for transforming growth factor beta (TGF beta) or
      interleukin 2 (IL-2) on disease activity in the MRL/lpr/lpr murine model of
      systemic lupus erythematosus (SLE). Monthly injections of plasmids cDNA between 6
      and 26 weeks significantly elevated the serum levels of TGF beta (P < 0.005) and
      IL-2 (P < 0.05) compared with a control plasmid without insert. TGF beta encoding
      plasmid had beneficial effects in murine SLE with a prolonged survival of 70% at
      26 weeks compared with 40% in the control group, decreased anti-chromatin and
      rheumatoid factor antibodies and a 50% decrease in total IgG production. Renal
      function was improved with reduced BUN levels and kidney inflammation as
      estimated by an histologic score. Those beneficial effects occurred in the
      apparent absence of local or systemic side-effects. In contrast, IL-2 cDNA
      injections appeared harmful with a decreased survival to 20% at 26 weeks,
      enhanced total IgG synthesis and autoantibodies production with a 4.5-fold
      increase in antichromatin antibodies. These results indicate that somatic gene
      therapy may provide a simple, inexpensive and effective mechanism for the long
      term control of autoimmune diseases.

PMID- 8528226
TI  - Ontogeny of membrane cofactor protein: phenotypic divergence in the fetal heart.
AB  - Human adult cells are protected from complement-induced damage in part by
      membrane cofactor protein (MCP, CD46). To examine fetal characteristics which
      might influence autoantibody-mediated diseases acquired in utero, such as heart
      block in neonatal lupus, the tissue expression of MCP was studied. Using a high
      ratio of acrylamide:bisacrylamide, immunoblots of tissues from six fetuses (aged
      19-24 weeks) probed with rabbit anti-MCP antibodies revealed a band at 60 KD in
      addition to the known 65 KD and 55 KD isoforms which comprise the codominant
      allelic system of MCP. Five fetuses expressed the most common MCP polymorphism
      (predominance of the 65 KD isoform, upper band alpha-phenotype) in the kidney,
      spleen, liver and lung. In contrast, all hearts from these five fetuses
      demonstrated a different pattern in which there was a marked decrease in the
      intensity of the 65 KD band and accentuation of the lower molecular weight bands.
      In a sixth fetus, which expressed the second most common polymorphism (equal
      expression of the 65 KD and 55 KD MCP isoforms, alpha beta-phenotype), the heart
      was similar to the other tissues. These studies confirm the expression of MCP in
      early gestational life. Preferential expression of the MCP beta-isoform in the
      majority of fetal hearts irrespective of the phenotype of other organs, suggests
      tissue-specific RNA splicing or post-translational modification which may relate
      to autoantibody-mediated injury in diseases such as neonatal lupus.

PMID- 8528227
TI  - Dual inhibitory and stimulatory activities in serum from SLE patients and lupus
      mice that regulate the proliferation of an IL-2-dependent T cell line.
AB  - In serum and plasma from SLE patients, we have detected elevated levels of
      factors which regulate proliferative responses of CTLL cells to IL-2. Serum
      samples containing these factors have dose-dependent dual inhibitory and
      stimulatory activities on the proliferation of this IL-2-dependent T lymphocyte
      cell line. At high concentrations, the serum factors inhibit the proliferative
      responses of CTLL cells to IL-2. At low concentrations, they synergise with IL-2
      stimulating the growth of cells. Similar inhibitory activity, but with lower
      titre, was also found to be elevated in sera of some MRL/lpr mice, an animal
      model of SLE. Functional characterisation of the serum factors shows that: (1)
      the inhibitory activity cannot be neutralised by exogenous IL-2; (2) the
      stimulatory activity is not due to the presence of serum IL-2 but synergy of the
      factor with IL-2; (3) the factors bind directly to CTLL cells but they do not
      bind to protein A; and (4) the serum factors are not dialysable but heat labile.
      The possible pathological implications of the serum factors, particularly for the
      defective T cell functions in lupus disease, are discussed.

PMID- 8528228
TI  - Specific antiphospholipid antibodies (aPL) eluted from placentae of pregnant
      women with aPL-positive sera.
AB  - The mechanism by which antiphospholipid antibodies (aPL) cause recurrent
      pregnancy loss remains unclear. It has however been reported that aPL may affect
      cytotrophoblasts in vitro and thus direct placental damage might occur.
      Therefore, we investigated whether aPL are bound directly to placental tissues in
      patients with immunoglobulin G (IgG)-aPL positive sera. The material investigated
      comprised the placentae of six patients with a history of recurrent pregnancy
      loss and subclinical autoimmune disorder and one with systemic lupus
      erythematosus, who were treated with a combination of prednisolone and aspirin.
      Normal controls consisted of placentae derived from six women, negative for serum
      aPL, with no medical or obstetrical complication during their pregnancy. Five
      kinds of IgG- and IgM-antiphospholipid (anti-PS, PI, PA, PG and CL) antibodies
      were eluted from the placentae of both patients and controls, which were measured
      by enzyme-linked immunosorbent assay. IgG-aPL were detected in the placental
      eluates of four of seven (57%) patients, whereas IgM-aPL were not found in any.
      With respect to the pregnancy outcome of the four patients with IgG-aPL-positive
      placental eluates, one experienced intrauterine fetal death (IUFD) at 23 weeks of
      gestation and three demonstrated intrauterine growth retardation (IUGR). In
      contrast, the remaining three patients, evaluated negative for IgG-aPL in
      placental eluates, gave birth to one baby with IUGR and two appropriate-for-date
      babies. The placentae of the four mothers with IgG-aPL-positive placental eluates
      pathologically showed severe thrombotic findings. These results suggest that IgG
      aPL can directly bind to placental tissue and might cause pathologic damage
      resulting in IUFD or IUGR.

PMID- 8528229
TI  - The presence of antiphospholipid antibodies in acute myocardial infarction.
AB  - This study was undertaken to determine if there is an association between
      increased titers of five different antiphospholipid antibodies (aPLA) in young
      patients' sera and the occurrence of acute myocardial infarction (AMI).
      Antibodies to anticardiolipin (aCL), anti-phosphatidylserine (aPS),
      antiphosphatidylinositol (aPI), anti-phosphatidylcholine (aPC), and anti
      phosphatidylethanol amine (aPEA) were measured in 214 patients (102 patients, 102
      healthy controls and 10 patients with antiphospholipid syndrome). These
      antibodies were measured twice (within 4h of onset of acute myocardial ischemic
      chest pain and 3 months after the myocardial infarction) by enzyme linked
      immunosorbent assay (ELISA). Elevated titers of four different aPLA were detected
      in 6.9% of all patients with AMI on hospitalization. Titers of aPLA in AMI were
      elevated in the younger age group < 50 years old (P < 0.001) and in men only (not
      statistically significant). No correlation was found between the presence of aPLA
      and cardiovascular risk factors (smoking, hypertension, diabetes mellitus and
      hyper-cholesterolemia). Three of the seven patients with increased titers of aPLA
      did not have any other cardiovascular risk factors. The titers of aPLA were
      within normal range 3 months after AMI. Evidence of significantly elevated titers
      of different aPLA at the early stage of AMI suggests that these autoantibodies
      are present before the AMI and are not secondary to them. The disappearance of
      the elevated aPLA 3 months after AMI may be due to an absorption effect or
      possibly a cyclic phenomenon similarly found in other autoimmune diseases. aPLA
      may be an additional risk factor for AMI, and should especially be considered in
      a patient of the younger age group without apparent cardiovascular risk factors.

PMID- 8528230
TI  - Autoantibodies to topoisomerase I in a patient with systemic lupus erythematosus
      without features of scleroderma.
AB  - We report a woman with systemic lupus erythematosus (SLE) with diffuse
      proliferative glomerulonephritis and anti-dsDNA antibodies whose serum contained
      autoantibodies specific for the phosphorylated form of RNA polymerase II (RNAP
      IIO), Su and ribosomal P antigen, as well as anti-topoisomerase I antibodies, a
      marker for scleroderma (SSc). Over 6 years, the patient exhibited clinical
      manifestations consistent with SLE without clinical evidence of scleroderma. The
      reactivity of her serum autoantibodies with the phosphoproteins ribosomal P,
      topoisomerase I, and RNAP IIO is consistent with recognition of autoepitopes
      comprised in part of phosphate groups. This may explain the unexpected
      coexistence of marker autoantibodies for SLE and scleroderma, possibly with
      implications for the mechanisms of autoantibody generation.

PMID- 8528231
TI  - Tricuspid valve steno-insufficiency in systemic lupus erythematosus.
AB  - We describe a case of isolated tricuspid steno-insufficiency, diagnosed by
      transthoracic echocardiography, in a 43-year-old woman affected by systemic lupus
      erythematosus. Other similar cases were never previously reported.

PMID- 8528232
TI  - Hemichorea in systemic lupus erythematosus: significance of MRI findings.
AB  - A young man with systemic lupus (SLE) developed hemichorea 13 years after the
      onset of his illness. For the first time in the course of his illness he had a
      positive test for anticardiolipin antibodies (aCL). Magnetic resonance imaging
      (MRI) of his brain showed lesions of presumed vascular cause in the ipsilateral
      basal ganglia. The findings support the contention that an immune phenomenon,
      invisible on proton imaging by MRI, is responsible for the striatal neuronal
      activation. Chorea, the clinical expression of this activation, was probably
      blocked on the side previously affected by vascular pathology.

PMID- 8528233
TI  - Benign intracranial hypertension: a non-thrombotic complication of the primary
      antiphospholipid syndrome?
AB  - Benign intracranial hypertension is a rare complication of systemic lupus
      erythematosus often attributed to cerebral sinus thrombosis which impairs venous
      drainage and cerebrospinal fluid outflow. We report the case of a woman with a
      primary antiphospholipid syndrome who developed benign intracranial hypertension
      with no actual evidence of venous cerebral thrombosis and with no other possible
      cause for this clinical manifestation than high titres of anticardiolipin
      antibodies and a lupus anticoagulant.

PMID- 8528234
TI  - Lhermitte's sign in systemic lupus erythematosus.

PMID- 8528235
TI  - Symptomatic unilateral sacroiliitis in systemic lupus erythematosus.

PMID- 8528236
TI  - Budd-Chiari syndrome in the context of antiphospholipid syndrome: diagnostic and
      therapeutic implications.

PMID- 8528237
TI  - Third and long (QT)

PMID- 8528238
TI  - Chromosome arm painting probes.

PMID- 8528239
TI  - Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia
      sulphate transporter gene.

PMID- 8528240
TI  - A mutation in the gene encoding the alpha 2 chain of the fibril-associated
      collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2).

PMID- 8528241
TI  - Early neonatal death in mice homozygous for a null allele of the insulin receptor
      gene.

PMID- 8528242
TI  - Early copper-histidine treatment for Menkes disease.

PMID- 8528243
TI  - Microsatellites are subject to directional evolution.

PMID- 8528244
TI  - Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause
      cardiac arrhythmias.
AB  - Genetic factors contribute to the risk of sudden death from cardiac arrhythmias.
      Here, positional cloning methods establish KVLQT1 as the chromosome 11-linked
      LQT1 gene responsible for the most common inherited cardiac arrhythmia. KVLQT1 is
      strongly expressed in the heart and encodes a protein with structural features of
      a voltage-gated potassium channel. KVLQT1 mutations are present in affected
      members of 16 arrhythmia families, including one intragenic deletion and ten
      different missense mutations. These data define KVLQT1 as a novel cardiac
      potassium channel gene and show that mutations in this gene cause susceptibility
      to ventricular tachyarrhythmias and sudden death.

PMID- 8528245
TI  - Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is
      caused by mutations in the thiazide-sensitive Na-Cl cotransporter.
AB  - Maintenance of fluid and electrolyte homeostasis is critical for normal
      neuromuscular function. Bartter's syndrome is an autosomal recessive disease
      characterized by diverse abnormalities in electrolyte homeostasis including
      hypokalaemic metabolic alkalosis; Gitelman's syndrome represents the predominant
      subset of Bartter's patients having hypomagnesemia and hypocalciuria. We now
      demonstrate complete linkage of Gitelman's syndrome to the locus encoding the
      renal thiazide-sensitive Na-Cl cotransporter, and identify a wide variety of non
      conservative mutations, consistent with loss of function alleles, in affected
      subjects. These findings demonstrate the molecular basis of Gitelman's syndrome.
      We speculate that these mutant alleles lead to reduced sodium chloride
      reabsorption in the more common heterozygotes, potentially protecting against
      development of hypertension.

PMID- 8528246
TI  - Mapping genes for human personality.

PMID- 8528247
TI  - Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat.
AB  - Non-insulin dependent diabetes mellitus (NIDDM) is a major public health problem,
      but its aetiology remains poorly understood. We have performed a comprehensive
      study of the genetic basis of diabetes in the Goto-Kakizaki (GK) rat, the most
      widely used animal model of non-obese NIDDM. The genetic dissection of NIDDM
      using this model has allowed us to map three independent loci involved in the
      disease. In addition, we identify a major factor affecting body weight, but not
      glucose tolerance, on chromosome 7 and map a further 10 regions that are
      suggestive for linkage. We conclude that NIDDM is polygenic and fasting
      hyperglycaemia and postprandial hyperglycaemia clearly have distinct genetic
      bases.

PMID- 8528248
TI  - Chromosomal mapping of genetic loci associated with non-insulin dependent
      diabetes in the GK rat.
AB  - Goto-Kakizaki (GK) rats are a well characterized model for non-insulin dependent
      diabetes mellitus (NIDDM). We have used a combination of physiological and
      genetic studies to identify quantitative trait loci (QTLs) responsible for the
      control of glucose homeostasis and insulin secretion in a F2 cohort bred from
      spontaneously diabetic GK rats. The genetic dissection of NIDDM allowed us to map
      up to six independently segregating loci predisposing to hyperglycaemia, glucose
      intolerance or altered insulin secretion, and a seventh locus implicated in body
      weight. QTLs implicated in glucose tolerance and adiposity map to the same region
      of rat chromosome 1, and may indicate the influence of a single locus. Our study
      demonstrates that distinct combinations of genetic loci are responsible for
      different physiological characteristics associated with the diabetic phenotype in
      the GK rat, and it constitutes an important step for directing the search for the
      genetic factors involved in human NIDDM.

PMID- 8528249
TI  - Rat model contributes new loci for NIDDM susceptibility in man.

PMID- 8528250
TI  - Renal disease susceptibility and hypertension are under independent genetic
      control in the fawn-hooded rat.
AB  - Hypertension, diabetes and hyperlipidemia are risk factors for life-threatening
      complications such as end-stage renal disease, coronary artery disease and
      stroke. Why some patients develop complications is unclear, but only
      susceptibility genes may be involved. To test this notion, we studied crosses
      involving the fawn-hooded rat, an animal model of hypertension that develops
      chronic renal failure. Here, we report the localization of two genes, Rf-1 and Rf
      2, responsible for about half of the genetic variation in key indices of renal
      impairment. In addition, we localize a gene, Bpfh-1, responsible for about 26% of
      the genetic variation in blood pressure. Rf-1 strongly affects the risk of renal
      impairment, but has no significant effect on blood pressure. Our results show
      that susceptibility to a complication of hypertension is under at least partially
      independent genetic control from susceptibility to hypertension itself.

PMID- 8528251
TI  - Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde
      dehydrogenase gene.
AB  - Sjogren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder
      characterized by mental retardation, spasticity and ichthyosis. SLS patients have
      a profound deficiency in fatty aldehyde dehydrogenase (FALDH) activity. We have
      now cloned the human FALDH cDNA and show that it maps to the SLS locus on
      chromosome 17p11.2. Sequence analysis of FALDH amplified from fibroblast mRNA and
      genomic DNA from 3 unrelated SLS patients reveals distinct mutations, including
      deletions, an insertion and a point mutation. The cloning of FALDH and the
      identification of mutations in SLS patients opens up possibilities for developing
      therapeutic approaches to ameliorate the neurologic and cutaneous symptoms of the
      disease.

PMID- 8528252
TI  - Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p
      and 6q by the regressive approach.
AB  - The changes in the type of haemoglobin (Hb) produced during embryonic, fetal and
      adult life, have served as a paradigm for understanding the developmental
      regulation of human genes. A genetically determined persistence of fetal Hb
      synthesis has an ameliorating effect on beta thalassaemia and sickle cell
      anaemia, globally the commonest single gene disorders. The search for the
      putative gene(s) controlling the level of fetal Hb production has been extremely
      difficult because this trait may be influenced by several factors. We have
      studied a large kindred with hereditary persistence of fetal haemoglobin (HPFH).
      Using a genetic mapping strategy and statistical methods that account
      simultaneously for the effects of several genetic factors, we have demonstrated
      that in addition to the two factors (beta thalassaemia and Xmn I-G gamma site) on
      chromosome 11p, there is a third major genetic determinant for fetal Hb
      production localized on chromosome 6q.

PMID- 8528253
TI  - Mouse models, immunology, multiple sclerosis and myelination.

PMID- 8528254
TI  - Selective capture of acentric fragments by micronuclei provides a rapid method
      for purifying extrachromosomally amplified DNA.
AB  - The amplification and overexpression of a number of oncogenes is strongly
      associated with the progression of a variety of different cancers. We now present
      a strategy to purify amplified DNA on double minute chromosomes (DMs) to enable
      analysis of their prevalence and contribution to tumourigenesis. Using cell lines
      derived from four different tumour types, we have developed a general and rapid
      method to purify micronuclei that are known to entrap extrachromosomal elements.
      The isolated DNA is highly enriched in DM sequences and can be used to prepare
      probes to localize the progenitor single copy chromosomal regions. The capture of
      DMs by micronuclei appears to be dependent on their lack of a centromere rather
      than their small size.

PMID- 8528255
TI  - A protein linkage map of Escherichia coli bacteriophage T7.
AB  - Genome sequencing projects are predicting large numbers of novel proteins, whose
      interactions with other proteins must mediate the function of cellular processes.
      To analyse these networks, we used the yeast two-hybrid system on a genome-wide
      scale to identify 25 interactions among the proteins of Escherichia coli
      bacteriophage T7. Among these is a set of six interactions connecting proteins
      that function in DNA replication and DNA packaging. Remarkably, two genes,
      arranged such that one entirely overlaps the other and uses a different reading
      frame, encode interacting proteins. Several of the interactions reflect
      intramolecular associations of different domains of the same polypeptide,
      suggesting that the two-hybrid assay may be useful in the analysis of protein
      folding. This global approach to protein-protein interactions may be applicable
      to the analysis of more complex genomes whose sequences are becoming available.

PMID- 8528256
TI  - Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human
      personality trait of Novelty Seeking.

PMID- 8528257
TI  - A little lesson in growth regulation.

PMID- 8528258
TI  - Population and familial association between the D4 dopamine receptor gene and
      measures of Novelty Seeking.

PMID- 8528259
TI  - A two-hit model for developmental defects in Gorlin syndrome.

PMID- 8528261
TI  - The fragile X mental retardation protein is associated with ribosomes.

PMID- 8528260
TI  - Nonsense mutation in the human growth hormone-releasing hormone receptor causes
      growth failure analogous to the little (lit) mouse.

PMID- 8528262
TI  - Germline mutations in the homeobox gene EMX2 in patients with severe
      schizencephaly.

PMID- 8528263
TI  - Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma.

PMID- 8528264
TI  - Pharmacogenetics of cocaine: a critical review.
AB  - The development of genetic models to help explain individual differences in
      sensitivity to and susceptibility to misuse certain CNS active substances, like
      ethanol and psychostimulants, spans a brief, thirty-plus years. The first animal
      models involved inbred strains and selected lines of mice and rats and predicted
      genetic-based differential sensitivity to ethanol and its misuse in humans found
      a few years later. With drugs like cocaine, tracking genetic differences in
      sensitivity and misuse liability in humans is difficult because of legal
      problems. Genetically-defined animals, however, have shown most if not all of
      cocaine-related behavioural, neurophysiological and toxicological effects to
      evince wide variation with most effects being influenced by several genes. Thus,
      we argue that animal and human studies of individual differences in drug
      sensitivity be studied from both quantitative and molecular genetic approaches.
      For the former, new techniques involving recombinant inbred strains of rodents,
      genetic correlational analysis and quantitative trait loci analysis are
      particularly useful, especially as genetic synteny between rodents and humans
      becomes better described. Also, because drug effects are highly labile to
      environmental conditions as well as genetic-based individual differences,
      multivariate, systems level studies should be developed to provide more complete
      descriptive and mechanistic views of a multifaceted problem.

PMID- 8528265
TI  - Evidence for the polymorphic oxidation of debrisoquine and proguanil in a New
      Zealand Maori population.
AB  - The genetic oxidation polymorphisms of debrisoquine and proguanil were studied in
      a New Zealand Maori population. A bimodal distribution was observed in the 0-4 h
      urinary debrisoquine/4-hydroxydebrisoquine metabolic ratio. Of 101 Maori subjects
      phenotyped, five subjects (5%) were identified as poor metabolizers of
      debrisoquine, according to criteria established in studies of Caucasian
      populations. The prevalence of the debrisoquine poor metabolizer phenotype in the
      Maori appears to be similar to that reported for the Caucasian populations, but
      higher than that found in Asian (non-Caucasian) populations. The distribution of
      proguanil:cycloguanil (PG:CG) ratios obtained from 43 Maori subjects was highly
      skewed. Using a PG:CG ratio of 10 as the cut-off point, three Maori subjects (7%)
      were classified as poor metabolizers of proguanil. The incidence of the poor
      metabolizer phenotype of proguanil oxidation of 7% seems to be higher in Maori
      compared with Caucasian populations, but this is lower than the usual ranges (15
      35%) reported in Asian populations.

PMID- 8528266
TI  - Identification of an NAD(P)H:quinone oxidoreductase polymorphism and its
      association with lung cancer and smoking.
AB  - The enzyme NAD(P)H:quinone oxidoreductase (NQO1) catalyses bioreduction and
      bioactivation reactions. A mutation in the NQO1 gene had previously been
      demonstrated in a cancer cell line with reduced NQO1 activity. In this study,
      several regions of the NQO1 locus were examined for constitutional variation at
      the DNA level. The previously described mutation in exon 6 was detected by the
      single-strand conformation polymorphism technique. This was confirmed by
      sequencing to result from a C-->T substitution. Genotype analysis in the Centre
      d'Etude Polymorphisme Humain (CEPH) reference panel revealed two alleles with
      frequencies of 0.87 and 0.13 and demonstrated Mendelian transmission. Genotype
      distributions were consistent with Hardy-Weinberg equilibrium. Linkage analysis
      mapped the gene locus to chromosome 16q. NQO1 was felt to be a candidate gene for
      the susceptibility to lung cancer, given its potential role in protection against
      carcinogenic compounds. The frequency of NQO1 variants was examined in 150 lung
      cancer cases and in two reference populations. The allele distribution in CEPH
      parent controls was significantly different from cases (chi 2 = 5.52, p = 0.019),
      but no difference was noted between cases and a healthy local reference
      population. When the local reference distribution was stratified on smoking
      status, a significant difference was observed (chi 2 = 3.88, p = 0.048).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8528267
TI  - Lung cancer and mutations at the polymorphic NAT2 gene locus.
AB  - The prevalence of seven point mutations on the polymorphic NAT2 gene was studied
      in DNA from 108 patients with histologically proved bronchogenic carcinoma and
      243 healthy controls. By means of a mutation-specific polymerase chain reaction
      analysis, the wild-type and fourteen mutant allelic variants of the NAT2 gene
      were identified. The prevalence for the poor acetylator genotypes in patients and
      control subjects were similar, however the frequency of mutant alleles was higher
      in patients with lung cancer. This was attributable to an increase in the
      prevalence of the allelic variants 590A and 341C + 481T + 803G among patients (p
      < 0.05 and 0.06, respectively). These allelic variants were at increased
      frequency in patients with adenocarcinoma, squamous cell or small cell lung
      cancer. Subjects poor acetylators that are homozygous for the allelic variant
      341C + 481T + 803G seem to be at increased risk to develop lung cancer (odds
      ratio; 95% CI = 1.75; 0.99-3.12). We conclude that the acetylator status is not a
      major factor in lung cancer risk, however the presence of the 341C + 481T + 803G
      and the 590A alleles of the polymorphic NAT2 gene may be a secondary risk factor
      for the development of lung cancer.

PMID- 8528268
TI  - Detection of the poor metabolizer-associated CYP2D6(D) gene deletion allele by
      long-PCR technology.
AB  - The cytochrome P450 enzyme debrisoquine 4-hydroxylase metabolizes many different
      classes of commonly used drugs, such as antidepressants and neuroleptics.
      Deficient hydroxylation of debrisoquine, known as the poor metabolizer (PM)
      phenotype, affects 5-10% of Caucasians and may lead to adverse reactions upon
      administration of drugs in standard doses. This autosomal recessive metabolic
      deficiency is caused by the possession of two PM-associated mutations in the
      human CYP2D6 gene locus coding for the enzyme. These mutations include at least
      four different single base mutations and two different large gene deletion
      alleles. The single base mutations can be rapidly detected by PCR methods. In
      contrast, the large gene deletions have so far only been directly identified by
      RFLP analysis. By the use of sequence data previously published by others, we
      report here an alignment of different CYP2D alleles to focus on the presence of
      almost completely identical sequences immediately downstream of both CYP2D7 and
      CYP2D6 which may seriously complicate and interfere with PCR-based detection of
      the gene deletion. Based on this analysis, we have developed a rapid assay which,
      for the first time, detects the 13kb (also called 11.5 kb) Xba I gene deletion
      allele by the use of long-PCR technology. The primers were designed to amplify a
      3.5 kb PCR product in the presence of this D6(D) allele. We have evaluated the
      method on 23 different DNA samples heterozygous (n = 22) or homozygous (n = 1)
      for the 13 kb gene deletion allele (previously typed by RFLP analyses). All
      samples were correctly identified by the assay. The PCR method did not detect the
      rare 11 kb Xba I gene deletion allele (n = 5), and there was no false positive
      amplification from deletion negative DNA samples (n = 47). This sensitive and
      specific PCR-based assay for detection of the D6(D) allele will improve the
      scientific and clinical use of CYP2D6 genotyping.

PMID- 8528269
TI  - Human variability in hepatic glutathione S-transferase-mediated conjugation of
      aflatoxin B1-epoxide and other substrates.
AB  - Hepatic cytosolic fractions prepared from 14 human donors were analysed for
      glutathione S-transferase (GST) activity towards synthetic aflatoxin B1-8,9
      epoxide (AFBO). In addition, GST-AFBO activity of pooled human liver cytosols was
      compared with rat, hamster, and mouse liver cytosol GST-AFBO activities.
      Consistent with previous studies, human liver cytosolic GSTs exhibited little
      activity towards AFBO. Hepatic GST-AFBO activities of rat, hamster, and mouse
      were 48-, 56-, and 312-fold greater, respectively, than observed for human liver
      using synthetic AFBO, and 70-, 465-, and 3545-fold greater, respectively, than
      observed for human liver using microsomally-generated AFBO. Furthermore, there
      was a 58-fold variation in hepatic GST-AFBO activities among the 14 human samples
      using synthetic AFBO as a substrate. Large interindividual variations were also
      observed with respect to GST activities towards bromosulfophthalein (BSP, 92-fold
      variation) and 3,4-dichloronitrobenzene (DCNB, 36-fold variation). Lesser
      interindividual variations were observed with respect to human liver GST
      activities towards benzo(a)pyrene-4,5-oxide (BaPO, 9-fold variation), 1-chloro
      2,4-dinitrobenzene (CDNB, 8.5-fold variation), cumene hydroperoxide (CHP, 5-fold
      variation), and p-nitrophenyl acetate (NPA, 4-fold variation). No correlation was
      found among GST-AFBO activities and the presence of GST mu as determined by
      enzyme-linked immunosorbent assay (ELISA) or GST-trans-stilbene oxide (TSO)
      catalytic activity. Our observations support those of previous studies indicating
      that human liver cytosolic GSTs are relatively ineffective at conjugating AFBO.
      Furthermore, our data indicate that humans exhibit large inter-individual
      differences with respect to hepatic cytosolic GST conjugation of AFBO and certain
      other GST substrates.

PMID- 8528270
TI  - Comparison of substrate metabolism by wild type CYP2D6 protein and a variant
      containing methionine, not valine, at position 374.
AB  - We have analysed kinetic parameters of cDNA-derived CYP2D6 proteins derived from
      the original CYP2D6 cDNA isolate (Gonzalez FJ et al. Nature 1988: 331, 442-446)
      which contains methionine at position 374 (CYP2D6-Met) and a modified cDNA which
      contains valine at position 374 (CYP2D6-Val). This latter protein is predicted
      from the CYP2D6 genomic sequence. Several quantitative differences, but no
      qualitative differences in metabolism were observed. CYP2D6-Met was found to have
      a two-fold lower Km and a three-fold lower turnover rate for (R)(+)-bufuralol 1'
      hydroxylation as compared to CYP2D6-Val. In contrast, CYP2D6-Met and CYP2D6-Val
      had a similar Km for debrisoquine 4-hydroxylation while CYP2D6-Val had an 18-fold
      higher turnover rate. CYP2D6-Val and CYP2D6-Met had similar Kms for metoprolol
      but CYP2D6-Val showed a three-fold higher capacity for the O-demethylation
      reaction compared to alpha-hydroxylation which is more similar to that seen in
      human liver. In the case of sparteine, CYP2D6-Val and CYP2D6-Met showed similar
      capacities for formation of the 2-dehydrosparteine metabolite but the Km value
      for CYP2D6-Met was six-fold higher than that for CYP2D6-Val. Kinetic differences
      between CYP2D6-Met and CYP2D6-Val were further probed by examination of apparent
      Ki for inhibition of (R,S)(+/-)-bufuralol 1'-hydroxylation. Similar Ki values
      (within a factor of three) were observed for perhexiline and (R,S)-propranolol
      while quinidine and dextromethorphan were 8.5-fold and 21-fold more effective
      inhibitors of CYP2D6-Val relative to CYP2D6-Met. An allele specific polymerase
      chain reaction assay was developed for the CYP2D6-Met allele. The CYP2D6-Met
      allele was not found among 83 individuals. In the aggregate, these data indicated
      that the CYP2D6-Val allele is the more common allele in human populations. The
      quantitative kinetic differences between these two enzymes appears most
      pronounced for substrates/inhibitors with rigid structures. CYP2D6-Val more often
      has a substantially lower Km and/or a substantially higher capacity to metabolize
      those substrates.

PMID- 8528271
TI  - Dysfunctional N-oxidation of trimethylamine and the influence of testosterone
      treatment in man.

PMID- 8528272
TI  - Cloning, sequencing and expression of NAT1 and NAT2 encoding genes from rapid and
      slow acetylator inbred rats.

PMID- 8528273
TI  - Genotypic and phenotypic determination of polymorphic glutathione transferase T1
      in a Swedish population.

PMID- 8528274
TI  - A slow acetylator genotype is a risk factor for sulphonamide-induced toxic
      epidermal necrolysis and Stevens-Johnson syndrome.

PMID- 8528275
TI  - Cellular localization of the Ca2+ binding TCH3 protein of Arabidopsis.
AB  - TCH3 is an Arabidopsis touch (TCH) gene isolated as a result of its strong and
      rapid upregulation in response to mechanical stimuli, such as touch and wind.
      TCH3 encodes an unusual calcium ion-binding protein that is closely related to
      calmodulin but has the potential to bind six calcium ions. Here it is shown that
      TCH3 shows a restricted pattern of accumulation during Arabidopsis vegetative
      development. These data provide insight into the endogenous signals that may
      regulate TCH3 expression and the sites of TCH3 action. TCH3 is abundant in the
      shoot apical meristem, vascular tissue, the root columella and pericycle cells
      that give rise to lateral roots. In addition, TCH3 accumulation in cells of
      developing shoots and roots closely correlates with the process of cellular
      expansion. Following wind stimulation, TCH3 becomes more abundant in specific
      regions including the branchpoints of leaf primordia and stipules, pith
      parenchyma, and the vascular tissue. The consequences of TCH3 upregulation by
      wind are therefore spatially restricted and TCH3 may function at these sites to
      modify cell or tissue characteristics following mechanical stimulation. Because
      TCH3 accumulates specifically in cells and tissues that are thought to be under
      the influence of auxin, auxin levels may regulate TCH3 expression during
      development. TCH3 is upregulated in response to low levels of exogenous indole-3
      acetic acid (IAA), but not by inactive auxin-related compounds. These results
      suggest that TCH3 protein may play roles in mediating physiological responses to
      auxin and mechanical environmental stimuli.

PMID- 8528276
TI  - FLP recombinase in transgenic plants: constitutive activity in stably transformed
      tobacco and generation of marked cell clones in Arabidopsis.
AB  - FLP site-specific recombinase was expressed in stably transformed tobacco and
      Arabidopsis. FLP-expressing tobacco lines were crossed with other transformed
      tobacco lines that contained a stably integrated FLP recognition target
      construct(s). The target construct consisted of two directly-oriented FLP
      recognition targets (FRTs), flanking a hygromycin resistance cassette located
      between a GUS coding region and an upstream 35S CaMV promoter. Excision of the
      hygromycin resistance cassette by FLP-mediated recombination between FRTs brings
      the GUS coding region under the transcriptional control of the CaMV 35S promoter.
      In the absence of FLP-mediated recombination, the GUS gene is transcriptionally
      silent. GUS activity was observed in the progeny of all crosses made between FLP
      recombinase-expressing and target-containing tobacco lines, but not in the selfs
      of parents. The predicted recombination product remaining after excision was
      confirmed by PCR and Southern analysis. In Arabidopsis, inducible expression of
      FLP recombinase was achieved from the soybean Gmhsp 17.6L heat-shock promoter.
      Heat-shock induction of FLP expression in plants containing the target construct
      led to activation of constitutive GUS expression in a subset of cells, whose
      progeny, therefore, were GUS-positive. A variety of clonal sectors were produced
      in plants derived from seed that was heat-shocked during germination. The ability
      to control the timing of GUS activation was demonstrated by heat-shock of
      unopened flower heads which produced large sectors. It was concluded that heat
      shock-induced expression of FLP recombinase provides a readily controllable
      method for generating marked clonal sectors in Arabidopsis, the size and
      distribution of which reflects the timing of applied heat-shock.

PMID- 8528277
TI  - Mutations throughout an Arabidopsis blue-light photoreceptor impair blue-light
      responsive anthocyanin accumulation and inhibition of hypocotyl elongation.
AB  - This paper reports the characterization of novel mutations within the Arabidopsis
      thaliana HY4 gene, which has previously been shown to encode a protein (CRY1)
      with characteristics of a blue-light photoreceptor. Several point mutations were
      identified within the amino-terminal domain of CRY1--this region of CRY1 has high
      homology to photolyase and is likely to be involved in blue-light-mediated
      electron transfer. Mutations were found within the region of homology to the
      known chromophore binding domains of photolyase. Point mutations within the 200
      amino acid carboxy-terminal extension distinguishing CRY1 from photolyase,
      likewise disrupt function of the protein. CRY1 was originally defined as the
      photoreceptor responsible for blue-light-mediated inhibition of hypocotyl
      elongation and we now report that anthocyanin accumulation in germinating
      seedlings is an additional phenotype under the control of this photoreceptor-
      this is shown to be mediated in part by modulation of mRNA levels of chalcone
      synthase, one of the anthocyanin biosynthetic enzymes. The effect of the novel
      mutations on both inhibition of hypocotyl elongation and anthocyanin biosynthesis
      have been evaluated, and it is demonstrated that mutations with less severe
      effects on hypocotyl elongation show a similarly reduced effect on anthocyanin
      biosynthesis. These results are consistent with the cryptochrome photoreceptor
      mediating multiple regulatory pathways by the same primary mode of action.

PMID- 8528278
TI  - Analysis of Arabidopsis mutants deficient in flavonoid biosynthesis.
AB  - Eleven loci that play a role in the synthesis of flavonoids in Arabidopsis are
      described. Mutations at these loci, collectively named transparent testa (tt),
      disrupt the synthesis of brown pigments in the seed coat (testa). Several of
      these loci (tt3, tt4, tt5 and ttg) are also required for the accumulation of
      purple anthocyanins in leaves and stems and one locus (ttg) plays additional
      roles in trichome and root hair development. Specific functions were previously
      assigned to tt1-7 and ttg. Here, the results of additional genetic, biochemical
      and molecular analyses of these mutants are described. Genetic map positions were
      determined for tt8, tt9 and tt10. Thin-layer chromatography identified tissue-
      and locus-specific differences in the flavonols and anthocyanidins synthesized by
      mutant and wild-type plants. It was found that UV light reveals distinct
      differences in the floral tissues of tt3, tt4, tt5, tt6 and ttg, even though
      these tissues are indistinguishable under visible light. Evidence was also
      uncovered that tt8 and ttg specifically affect dihydroflavonol reductase gene
      expression. A summary of these and previously published results are incorporated
      into an overview of the genetics of flavonoid biosynthesis in Arabidopsis.

PMID- 8528279
TI  - MYB.Ph3 transcription factor from Petunia hybrida induces similar DNA
      bending/distortions on its two types of binding site.
AB  - MYB.Ph3 from Petunia is a member of the MYB transcription factor family that
      recognizes two types of binding site, resembling direct and inverted repeats of
      the motif GTTA, respectively, and flanked on their 5' side by an A-rich sequence.
      In this study, it is shown that MYB.Ph3 induces similar conformational changes in
      both of its DNA-binding sites. Circular permutation assays indicate that the
      center of the distortions induced by MYB.Ph3 maps near the center of either
      MYB.Ph3-binding site. The degree of the distortion induced by MYB.Ph3 appears to
      be greatly affected by regions of the protein other than the DNA-binding domain,
      and differs from the distortion caused by animal c-MYB. Phasing analysis reveals
      that part of the distortion induced by MYB.Ph3 is DNA bending, oriented towards
      the minor groove, as is the case of its animal counterpart, c-MYB. DNA-binding by
      both MYB.Ph3 and animal c-MYB is more efficient in the presence of Ba2+, a
      divalent cation known to promote/stabilize DNA bending, than in the presence of
      other cations which do not favor this distortion, such as Na+ and Mg2+. In
      addition, both MYB proteins show higher affinity to selectively nicked DNA, which
      has increased DNA flexibility, strongly suggesting that DNA binding by these MYB
      proteins and DNA structural properties are mutually influenced.

PMID- 8528280
TI  - The minimal ribosomal RNA gene promoter of Arabidopsis thaliana includes a
      critical element at the transcription initiation site.
AB  - The genes encoding the precursor of 18S, 5.8S and 25S ribosomal RNAs are
      transcribed in the nucleolus by RNA polymerase I. Unlike rRNA gene promoters in
      animals which differ substantially across species boundaries, plant rRNA gene
      promoters share sequence similarity for several nucleotides upstream and
      downstream of the transcription start site (+ 1). The conserved sequence consists
      of a near-consensus TATA box, a critical promoter element of most genes
      transcribed by RNA polymerase II and certain genes transcribed by RNA polymerase
      III, followed by a cluster of four to six guanosines. Using transient expression
      of cloned promoter deletions in Arabidopsis thaliana protoplasts, it is shown
      that the 5' boundary of the Arabidopsis rRNA gene promoter is located between -55
      and -33 and the 3' promoter boundary is approximately +6. The critical role of
      the TATA element at the initiation site was demonstrated by altering this region
      using tandem point mutations within constructs containing essentially complete
      intergenic spacer sequences from -2590 to +6. The initiation site mutations
      either abolished transcription or dramatically reduced transcript abundance
      relative to the wild-type promoter. In some mutants, transcription initiation was
      shifted to a new site, suggesting a role for the TATA-like initiator region in
      both start site selection and promoter strength. It is suggested that minimal
      rRNA gene promoters might be similar in design to minimal promoters of protein
      encoding genes, many of which utilize an initiator element, or INR, as an
      important promoter element located directly at the transcription start site.

PMID- 8528281
TI  - Identification of genes required for pollen-stigma recognition in Arabidopsis
      thaliana.
AB  - In higher plants, cell-cell recognition reactions taking place following
      pollination allow the selective restriction of self-pollination and/or
      interspecific pollination. Many of these systems function by regulating the
      process of water transfer from the cells found at the stigmatic surface to the
      individual pollen grain. Interspecific pollination studies on the cruciferous
      weed Arabidopsis thaliana revealed only a broad specificity of pollen recognition
      such that pollen from all tested members of the crucifer family were recognized,
      whereas pollen from almost all other species failed to hydrate. Genetic analysis
      of A. thaliana has identified three genes that are essential for this recognition
      process. Recessive mutations in any of these genes result in male sterility due
      to the production of pollen grains that fail to hydrate when placed on the
      stigma, but that are capable of hydrating and growing a pollen tube in vitro.
      Results from mixed pollination experiments suggest that the mutant pollen grains
      specifically lack a functional pollen-stigma recognition system. All three
      mutations described also result in a defect in the wax layer normally found on
      stems and leaves, similar to previously described eceriferum (cer) mutations.
      Genetic complementation and mapping experiments demonstrated that the newly
      identified mutants are allelic to the previously identified genes cer1, cer3 and
      cer6. TEM analysis of the ultrastructure of the pollen coating revealed that all
      of the mutant pollen grains bear coatings of normal thickness and that tryphine
      lipid droplets are missing in cer1-147, are reduced in size in cer6-2654 and
      appear normal in cer3-2186.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528282
TI  - Multiple serine phosphorylation sites on the 30 kDa TMV cell-to-cell movement
      protein synthesized in tobacco protoplasts.
AB  - p30, the protein required for cell-to-cell movement of tobacco mosaic virus
      (TMV), has a slightly reduced mobility on SDS-polyacrylamide gels when isolated
      by immunoprecipitation from TMV-infected protoplasts compared with that of p30
      translated from viral RNA in vitro. Further investigation established a probable
      cause for the difference in mobility between the two: protoplasts incorporate
      [32P]orthophosphate into p30 at multiple sites, predominantly as phosphoserine.
      Tryptic peptide mapping reveals at least five internal phosphopeptides in p30,
      besides the C-terminal tryptic phosphopeptide already reported, involving at
      least two distinct domains of the protein (at residues 61-114 and residues 212
      231), which may be substrates for different protein kinases. These structural
      results are consistent with a three-domain model for the TMV movement protein
      with two regulatory domains similar to that recently proposed on genetic grounds
      for dianthovirus movement proteins.

PMID- 8528283
TI  - Specification of chimeric flowering shoots in wild-type Arabidopsis.
AB  - Within wild-type Arabidopsis populations, a subset of the plants were found to
      have a single chimeric shoot on their primary shoot axes. The chimeric shoots
      were located below the lowest primary-axis flower; and they exhibited features of
      both flowers and paraclades (lateral flowering shoots). Morphological analyses of
      chimeric shoots indicated that they developed from single primordia. In each
      chimeric shoot, the side furthest from the apical meristem was specified as
      'flower'--while the side closest to the meristem was specified as 'paraclade'-
      suggesting that a stimulus from outside the apical meristem can directly induce
      primordia to develop as flowers. It is concluded that the development of the
      teratological chimeric shoots resulted from the overlap of the vegetative and
      floral specification processes within single primordia.

PMID- 8528284
TI  - A dinucleotide mutation in dihydrodipicolinate synthase of Nicotiana sylvestris
      leads to lysine overproduction.
AB  - By applying a mutagenesis/selection procedure to obtain resistance to a lysine
      analog, S-(2-aminoethyl)L-cysteine (AEC), a lysine overproducing mutant in
      Nicotiana sylvestris was isolated. Amino acid analyses performed throughout plant
      development and of different organs of the N. sylvestris RAEC-1 mutant, revealed
      a developmental-dependent accumulation of free lysine. Lysine biosynthesis in the
      RAEC-1 mutant was enhanced due to a lysine feedback-desensitized
      dihydrodipicolinate synthase (DHDPS). Several molecular approaches were
      undertaken to identify the nucleotide change in the dhdps-r1 gene, the mutated
      gene coding for the lysine-desensitized enzyme. The enzyme was purified from wild
      type plants for amino end microsequencing and 10 amino acids were identified.
      Using dicotyledon dhdps probes, a genomic fragment was cloned from an enriched
      library of DNA from the homozygote RAEC-1 mutant plant. A dhdps cDNA, putatively
      full-length, was isolated from a tobacco cDNA library. Nucleotide sequence
      analyses confirmed the presence of the previously identified amino end preceded
      by a chloroplast transit peptide sequence. Nucleotide sequence comparisons,
      enzymatic and immunological analyses revealed that the tobacco cDNA corresponds
      to a normal type of DHDPS, lysine feedback-regulated, and the genomic fragment to
      the mutated DHDPS, insensitive to lysine inhibition. Functional complementation
      of a DHDPS-deficient Escherichia coli strain was used as an expression system.
      Reconstruction between the cDNA and genomic fragment led to the production of a
      cDNA producing an insensitive form of DHDPS. Amino acid sequence comparisons
      pointed out, at position 104 from the first amino acid of the mature protein, the
      substitution of Asn to Ileu which corresponds to a dinucleotide mutation. This
      change is unique to the dhdps-r1 gene when compared with the wild-type sequence.
      The identification of the nucleotide and amino acid change of the lysine
      desensitized DHDPS from RAEC-1 plant opens new perspectives for the improvement
      of the nutritional value of crops and possibly to develop a new plant selectable
      marker.

PMID- 8528285
TI  - Expression of a single-chain Fv antibody against abscisic acid creates a wilty
      phenotype in transgenic tobacco.
AB  - The plant hormone abscisic acid (ABA) participates in the control of several
      important physiological processes in plants such as stomata regulation, seed
      dormancy and stress tolerance. A new strategy was developed to study these
      phenomena by blocking abscisic acid with intracellularly expressed specific
      single-chain variable fragment (scFv) antibodies. Here evidence is presented that
      the expression of single-chain Fv antibodies against abscisic acid in the
      endoplasmic reticulum of transgenic tobacco cells leads to a wilty phenotype.
      Stomatal conductance is increased at high CO2 concentrations dependent on the
      level of antibody expression in leaves. Symptoms of abscisic acid deficiency were
      generated in the transformants although they have even higher levels of abscisic
      acid than wild-type plants.

PMID- 8528286
TI  - Molybdenum co-factor biosynthesis: the Arabidopsis thaliana cDNA cnx1 encodes a
      multifunctional two-domain protein homologous to a mammalian neuroprotein, the
      insect protein Cinnamon and three Escherichia coli proteins.
AB  - The molybdenum co-factor (Moco) is an essential part of all eukaryotic
      molybdoenzymes. It is a molybdopterin and reveals the same principal structure in
      eubacteria, archaebacteria and eukaryotes. This paper reports the isolation of
      cnx1, a cDNA clone of Arabidopsis thaliana which complements the Escherichia coli
      Moco mutant mogA. The mapping data of this cDNA correlate well with the mapping
      position of the A. thaliana molybdenum co-factor locus chl6. As mutants in chl6
      are known to be repairable by high concentrations of molybdate, the defective
      gene is very likely to be involved in the last step of Moco biosynthesis, that
      is, the insertion of molybdenum into molybdopterin. The protein encoded by cnx1
      shows a two-domain structure: the N-terminal domain is homologous to the E. coli
      Moco protein MoeA, the C-terminal domain is homologous to the E. coli Moco
      proteins MoaB and MogA, respectively. These homologies show that part of the
      prokaryotic Moco biosynthetic pathway accomplished by monofunctional proteins in
      E. coli, is performed by a single multifunctional protein in eukaryotes. In
      addition Cnx1 is homologous to the eukaryotic proteins Gephyrin, a rat
      neuroprotein, and Cinnamon, a Drosophila protein with a function in Moco
      biosynthesis. These proteins also show a two-domain structure but the order of
      the domains is inversed as compared with Cnx1. Southern analysis indicates the
      existence of at least one further member, in addition to the cnx1 gene, of this
      novel gene family in the Arabidopsis genome.

PMID- 8528287
TI  - The CIC library: a large insert YAC library for genome mapping in Arabidopsis
      thaliana.
AB  - A new Arabidopsis thaliana (ecotype Columbia) genomic library has been
      constructed in Yeast Artificial Chromosomes: the CIC library (for CEPH, INRA and
      CNRS). Optimization of plant culture conditions and protoplast preparation
      allowed the recovery of large amounts of viable protoplasts. Mechanical shearing
      of DNA was minimized by isolation of DNA from protoplasts embedded in agarose.
      Cloning of large inserts was favored by including two successive size
      fractionation steps (after partial EcoRI digestion and after ligation with the
      vector arms), which selected DNA fragments larger than 350 kb. The library
      consists of 1152 clones with an average insert size of 420 kb. Clones carrying
      chloroplast DNA and various nuclear repeated sequences have been identified.
      Twenty-one per cent of the clones are found to contain chloroplast DNA.
      Therefore, the library represents around four nuclear genome equivalents. The
      clones containing 5S rDNA genes, 18S-25S rDNA sequences and the 180 bp
      paracentromeric repeated element account for 3.6%, 8.9% and 5.8%, respectively.
      Only one clone was found to carry the 160 bp paracentromeric repeated element.
      Given the smaller size of clones carrying Arabidopsis repeated DNA, the average
      size of remaining clones is around 480 kb. The library was screened by PCR
      amplification using pairs of primers corresponding to sequences dispersed in the
      genome. Seventy out of 76 pairs of primers identified from one to seven YAC
      clones. Thus at least 92% of the genome is represented in the CIC library. The
      survey of the library for clones containing unlinked DNA sequences indicates that
      the proportion of chimeric clones is lower than 10%.

PMID- 8528288
TI  - Construction of an equalized cDNA library from Arabidopsis thaliana.
AB  - Using a kinetic approach, a cDNA library composed of almost equal representations
      of all genes expressed in the aerial parts of 2-week-old Arabidopsis was
      constructed. A cDNA was synthesized with an oligo dT primer containing a Notl
      site. A linker containing the nucleotide sequence of Sse8387I which recognizes
      octanucleotides was added at the ends of the synthesized cDNA. The cDNA was
      amplified by the polymerase chain reaction (PCR), denatured, and reassociated
      under modified conditions. Thereafter, the remaining single-stranded DNA was
      converted to double-stranded DNA and amplified by PCR. These equalization steps
      were repeated three times and the products were cloned unidirectionally into a
      plasmid vector. Equalization was evaluated by colony hybridization and DNA
      sequencing. This approach will be applicable to construct a cDNA library suitable
      for subtraction, differential screening, and expression screening, especially for
      mRNA species present at very low concentrations in a few cells of a specific
      tissue.

PMID- 8528289
TI  - Green-fluorescent protein as a new vital marker in plant cells.
AB  - The green-fluorescent protein (GFP) from jellyfish Aequorea victoria has been
      used as a convenient new vital marker in various heterologous systems. However,
      it has been problematic to express GFP in higher eukaryotes, especially in higher
      plants. This paper reports that either a strong constitutive or a heat-shock
      promoter can direct the expression of GFP which is easily detectable in maize
      mesophyll protoplasts. In this single-cell system, bright green fluorescence
      emitted from GFP is visible when excited with UV or blue light even in the
      presence of blue fluorescence from the vacuole or the red chlorophyll
      autofluorescence from chloroplasts using a fluorescence microscope. No exogenous
      substrate, co-factor, or other gene product is required. GFP is very stable in
      plant cells and shows little photobleaching. Viable cells can be obtained after
      fluorescence-activated cell sorting based on GFP. The paper further reports that
      GFP can be detected in intact tissues after delivering the constructs into
      Arabidopsis leaf and root by microprojectile bombardment. The successful
      detection of GFP in plant cells relies on the use of a universal transcription
      enhancer from maize or the translation enhancer from tobacco mosaic virus (TMV)
      to boost the expression. This new reporter could be used to monitor gene
      expression, signal transduction, co-transfection, transformation, protein
      trafficking and localization, protein-protein interaction, cell separation and
      purification, and cell lineage in higher plants.

PMID- 8528290
TI  - Identification of amplified restriction fragment polymorphism (AFLP) markers
      tightly linked to the tomato Cf-9 gene for resistance to Cladosporium fulvum.
AB  - Using the technique of amplified restriction fragment polymorphism (AFLP)
      analysis, and bulked segregant pools from F2 progeny of the cross Lycopersicon
      esculentum (Cf9) x L. pennellii, approximately 42,000 AFLP loci for tight linkage
      to the tomato Cf-9 gene for resistance to Cladosporium fulvum have been screened.
      Analysis of F2 recombinants identified three markers which co-segregated with Cf
      9. The Cf-9 gene has recently been isolated by transposon tagging using the maize
      transposon Dissociation (Ds). Analysis of plasmid clones containing Cf-9 shows
      that two of these markers are located on opposite sides of the gene separated by
      15.5 kbp of intervening DNA. AFLP analysis provides a rapid and efficient
      technique for detecting large numbers of DNA markers and should expedite plant
      gene isolation by positional cloning and the construction of high-density
      molecular linkage maps of plant genomes.

PMID- 8528291
TI  - Pediatric urological cancer.

PMID- 8528292
TI  - Testicular germ-cell tumors in childhood and adolescence.
AB  - Testicular germ-cell tumors are relatively rare in childhood and adolescence,
      accounting for only 3.9% of all neoplasms. However, they have become a model for
      curable cancer. Furthermore, most of them have accurate serum markers [beta-human
      chorionic gonadotropin and alpha-fetoprotein], which provide in clinical stage I
      disease after semicastration a "wait and see" program. MAHO 82, 88, and 92 were
      cooperative studies on the treatment of testicular germ-cell tumors in childhood
      and adolescence. Between 1982 and 1993, 137 patients were registered. In all, 76
      patients suffered from yolk-sac tumors (YST); 30, from differentiated teratomas
      (TD); 29, from malignant teratomas of either intermediate (MTI), undifferentiated
      (MTU), or trophoblastic type (MTT); and 2, from seminomas. All patients received
      semicastration. Chemotherapy was given to 53 patients on the basis of disease
      stage and histology. Standard therapy consisted of four courses of vinblastine,
      bleomycin and cisplatin. However, if viable tumor was suspected after two
      courses, delayed laparotomy was performed (seven patients). If there was then
      complete tumor regression, standard therapy was continued (four patients). If
      there was an incomplete tumor response, the patients received as salvage therapy
      three courses of etoposide (VP-16), ifosfamide, and cisplatin (three patients).
      Among the patients with YST, 73 had stage I disease and 3, higher-stage disease;
      1 of these died due to tumor progression. In all, 56 patients were followed
      according to the "wait and see" policy; 9 of these needed a delayed standard
      chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528293
TI  - Progress and controversies in modern treatment of Wilms' tumors.
AB  - During the past 25 years the treatment of Wilms' tumors has been refined owing to
      a series of thoroughly performed clinical studies. The overall prognosis is
      currently 80% (long-term cures), but different therapeutic issues are still
      discussed controversially, especially the question of preoperative treatment. A
      number of different drugs have proved effective in the treatment of Wilms'
      tumors. It remains to be determined as to which drug combinations are the most
      effective for which histologic subtype and which stage of disease. It seems that
      these questions can be answered only if further studies consequently implicate
      analyses of early and long-term toxicities. The same is true for analyses of peri
      and postoperative complications. Radiotherapy plays a role in about 50% of
      cases. Special subtypes require modified strategies, and the optimal treatment
      for high-risk histologic types has not yet been found.

PMID- 8528294
TI  - Surgery in rhabdomyosarcoma of the bladder, prostate and vagina.
AB  - The treatment of bladder and prostate rhabdomyosarcoma (RMS) is highly
      controversial. Aside from chemotherapy, treatment modalities include conservative
      surgery, radical surgery, and pre-, intra-, or postoperative irradiation. Between
      1968 and 1993, 78 children with RMS were treated at our institution. In all, 22
      tumors were located in the urogenital tract (bladder/prostate, 13;
      paratesticular, 5; vaginal, 2; others, 2). Altogether, 6 patients had stage II
      disease; 7, stage III disease; and 2, stage IV disease. All 15 patients with RMS
      of the bladder, prostate, or vagina received chemotherapy, and 4 had additional
      radiotherapy. Surgery was also done in 10 patients; parents refused an operation
      in 3 cases. In all, 3 patients in an advanced tumor stage died of their disease.
      All other children currently show no evidence of disease (mean follow-up, 6
      years; range, from 2 months to 18 years). After chemotherapy, radical operative
      intervention with multiple biopsies (encircling the tumor)--in contrast to local
      tumor excision or partial resection--permits complete tumor resection followed by
      excellent long-term results. Following radiotherapy, often a consequence of organ
      sparing therapy, many complications ensued (60%); therefore, irradiation should
      be restricted to highly selected cases.

PMID- 8528295
TI  - Paratesticular rhabdomyosarcoma.
AB  - Even though rhabdomyosarcoma is the most common soft tissue sarcoma in children,
      accounting for 5-10% of all malignant disease in children under 15 years of age,
      so few cases are seen in a single institution that only the combined efforts of
      multicentre prospective trials made it possible fro adequate treatment schedules
      to be devised. Thank to this cooperation, survival rates have increased
      dramatically in recent decades; risk factors have been identified and treatment
      can now be adapted accordingly. This is especially true for the paratesticular
      rhabdomyosarcoma (PTRM), which now has a good prognosis in all stages. The
      striking similarity of tumor behavior and metastatic pathways to those in germ
      cell tumors in young male adults can provide us with more extensive data derived
      from a much larger group of patients. Recent data are gathered and evaluated in
      this review. Only in this way will it be possible to eliminate all treatment
      modalities known to be followed by severe sequelae, thus avoiding exposure of the
      patients to a therapy that carries more risks than the primary tumor itself.

PMID- 8528297
TI  - Testicular lymphoblastic leukemia/lymphoma.
AB  - Acute lymphoblastic leukemia is by far the most frequent malignant disease in
      children. In all, 5% of the boys affected will develop testicular disease either
      at initial presentation or during the disease course or as the first site of
      relapse. Modern treatment regimens have reduced the occurrence of testicular
      relapses, which was more frequent in the 1970s. There is no place for preventive
      measures for early recognition of testicular leukemia; routine biopsies have been
      abandoned, and prophylactic irradiation is not justified. In gross overt disease,
      orchiectomy is justified (1) in cases of huge bulky testicular disease, (2) if
      unilateral disease is probable, and (3) if radiation of the testes is refused. In
      malignant non-Hodgkin's lymphoma, orchiectomy may eventually be the best mode of
      diagnosing the disease if a boy presents with testicular enlargement. Standard
      local treatment, however, is irradiation of both testes, if both are affected.

PMID- 8528296
TI  - Malignant peripheral neuroectodermal tumors in urology.
AB  - During the past few years, a new tumor type has emerged in the pediatric and
      adolescent group of cancer patients, which has been designated malignant
      peripheral neuroectodermal tumor (MPNT). This tumor has some clinical and
      pathological signs in common with either soft-tissue sarcomas or classic Ewing's
      sarcoma, but is defined as a distinct entity because of its immunohistological
      characteristics. The tumor expresses neuronal markers, but the pattern varies:
      chromogranin, neuron-specific enolase, synaptophysin, protein S-100 and others.
      MPNT can occur in the urogenital region. The differential diagnosis on clinical
      grounds must include Ewing's and soft tissue sarcomas, and also Wilms' tumor and
      its variants. MPNT are often wide spread in the urogenital region when first
      diagnosed. Response to radiotherapy and combination chemotherapy is limited.
      Radical surgery is not always possible. The prognosis therefore remains rather
      poor at this time. A selection of MPNT patients is presented to demonstrate the
      various problems associated with this diagnosis. MRI and CT of all patients
      showed large tumors with direct infiltration of the surrounding structures. MRI
      is the best imaging modality for diagnosis and therapy monitoring in these
      tumors, because of its high soft-tissue contrast.

PMID- 8528298
TI  - Neuroblastoma.
AB  - Neuroblastoma, a disease primarily of infants and younger children, is a tumor
      deriving from sympathetic neuroblasts. The variety of tumor location, growth and
      biologic characteristics represents the clinical manifestations: the range
      comprises spontaneous regression up to eminently malignant development with
      resistance to any therapy. Sometimes the tumor is located in the patient's
      abdomen and becomes important as a differential diagnosis to the urologist. In
      recent years some important research work has been done, mainly in the field of
      molecular biology, supporting the hypothesis of two different types of
      neuroblastoma. Miscellaneous markers and imaging techniques with varying validity
      are available, but first of all the proof of elevated catecholamines in serum or
      urine, or the histology of the tumor, ensures the diagnosis. The international
      consensus for diagnosis, staging and response to treatment is a step of far
      reaching significance. The prognosis for most patients, especially for older
      patients with metastatic disease, remains poor, despite the combination of
      chemotherapy, radiation therapy and surgery. Further attempts are being made to
      identify the disease in a localized or early stage with the introduction of
      screening programs-whereby the benefit of the method is not statistically proven.
      Treatment trials focus at the moment on autologous peripheral blood cell and bone
      marrow transplantation.

PMID- 8528299
TI  - Damage to the urinary tract secondary to irradiation.
AB  - During the past two decades highly effective multimodality therapy with surgery,
      chemotherapy and irradiation has been developed through consecutive national and
      international study protocols for childhood genitourinary cancers, the model
      being Wilms' tumor. These studies represent a landmark achievement in the history
      of pediatric oncology and mark the success of multi-institutional efforts. Now
      that excellent survival rates have been established, current interest is now
      directed primarily at examination of survivors for long-term treatment
      complications and minimizing the side effects while preserving treatment
      efficacy. Treatment sequelae may not become evident until many years after the
      initial diagnosis of cancer and may have adverse influences on long-term survival
      and/or the quality of life of former patients. With radiotherapy being a mainstay
      on the stage adjusted therapy of primarily Wilms' tumor and rhabdomyosarcoma,
      morbidity may occur as either acute or chronic with the genitourinary tract as an
      important adversely affected vital organ system. The effects of radiotherapy in
      the treatment of genitourinary childhood cancers on the urinary tract are
      reviewed here.

PMID- 8528300
TI  - Functional electromyostimulation of the corpus cavernosum penis--preliminary
      results of a novel therapeutic option for erectile dysfunction.
AB  - Transcutaneous application of low-frequency electric current in the treatment of
      partially or temporarily denervated striated muscles is widely used to prevent or
      treat muscular atrophy. Due to the high regenerative capacity of smooth-muscle
      cells, this approach should be beneficial in the treatment of diseases with
      smooth-muscle degeneration due to partial denervation. Our study was done to
      evaluate the possible beneficial effect of transcutaneously applied low-frequency
      electric current on the corpus cavernosum penis in the treatment of erectile
      dysfunction. After a comprehensive workup, 21 patients with chronic erectile
      dysfunction (20/21 vasoactive nonresponders) received daily (3-5 x 20 min)
      transcutaneous functional electromyostimulation of the corpus cavernosum smooth
      muscles [FEMCC; zero-line symmetric impulses of trapezoid shape, 2-channel device
      with alternating stimulations; frequency (f), 10-20 Hz for channel I and 20-35 Hz
      for channel II; impulse duration (ti), 100-150 microseconds; approx. 12 mA; rise
      time, 0.5 s; stimulation time, 5 s/channel; pause between stimulations, 0.5 s. In
      all, 4/21 patients (19%) regained full spontaneous erections and another 3/21
      (14%) responded to vasoactive drugs after FEMCC. Overall, 14/21 were FEMCC
      failures, including 2 who subjectively "improved." In a similar group of patients
      who were evaluated during the same period but received no therapy, no spontaneous
      improvement in erectile function was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528301
TI  - Enucleation procedures in patients with multiple hereditary renal tumors.
AB  - Parenchymal sparing surgery is frequently appropriate in patients with familial
      renal tumors detected through the screening of affected kindreds. An enucleation
      technique for the rapid removal and hemostasis of multiple small renal tumors in
      patients with hereditary renal cancers is described herein. This technique
      facilitates the removal of multiple small superficial renal tumors, usually
      without hypothermia.

PMID- 8528302
TI  - Modification of the penile block.
AB  - Penile block is a recommended technique for circumcision in adults. The classic
      technique for performing this block fails to produce satisfactory analgesia in
      many cases, and pain sensation in the region of the prepuce persists. We propose
      a modified technique of penile block with the addition of infiltration of local
      anesthetic along the raphe of the penis up to the prepuce. In 30 patients (group
      1), circumcision was performed with the classic technique of penile block, and in
      100 patients (group 2) the modified technique was used. The frequency and
      intensity of pain during the operation were significantly higher in group 1,
      whereas patients in group 2 were practically pain-free. The discomfort
      experienced during performance of the block and in the postoperative period was
      equal in the two groups. We recommend this modified technique of penile block for
      circumcision in adults.

PMID- 8528304
TI  - One known Sarcocystis species and two found for the first time in red deer and
      wapiti (Cervus elaphus) in Europe.
AB  - Three species of sarcocysts from indigenous red deer and captive wapiti (Cervus
      elaphus, Cervidae) were characterized by means of light and electron microscopy.
      Two of them were found in this intermediate host species for the first time.
      Comparison of the literature and our results led to the conclusion that the three
      Sarcocystis species (Sporozoa, Sarcocystidae) should be provisionally designated
      as S. cf. grueneri, S. cf. capreolicanis and S. cf. hofmanni.

PMID- 8528303
TI  - Denovo urothelial carcinoma of the upper and lower urinary tract in kidney-
      transplant patients with end-stage analgesic nephropathy.
AB  - Patients with end-stage analgesic nephropathy bear a higher risk for urothelial
      cancer than do patients with other renal diseases. In a retrospective study in
      patients with analgesic nephropathy and kidney transplants we analyzed the
      prevalence and clinical course of de novo urothelial cancer. Diagnosis of
      analgesic nephropathy was based on the patients' history and clinical data. Only
      patients under cyclosporine treatment were included. Between 1968 and 1993, 2,371
      kidney transplants were performed on 2,072 patients in the Department of
      Abdominal and Transplant Surgery. The prevalence of analgesic nephropathy was
      3.1%. Of 65 patients with analgesic nephropathy and kidney transplants, 10
      (15.4%) developed urothelial carcinoma; 10.8%, bladder cancer; and 9.1%, renal
      pelvic cancer. The mean age at diagnosis was 56.1 years. Urothelial cancer
      occurred on average at 33.6 months posttransplantation. On average, 6 of 10
      patients with urothelial cancer died of the disease at 16.9 months after the
      diagnosis. All patients with urothelial bladder cancer had a muscle-infiltrating
      tumor of moderate or high grade. Since urothelial renal pelvic cancer occurred in
      9.1% of our patients with analgesic nephropathy and urological screening is
      insufficient in patients on dialysis, we suggest that prophylactic
      nephroureterectomy be performed on one side before transplantation and on the
      contralateral side at 3-6 months after transplantation. An aggressive approach is
      indicated in patients with urothelial cancer of the bladder.

PMID- 8528305
TI  - One known Sarcocystis species and one found for the first time in fallow deer
      (Dama dama).
AB  - Sarcocysts of free-ranging indigenous fallow deer (Dama d. dama) from northeast
      Germany and captive Persian fallow deer (Dama dama mesopotamica) from the Zoo
      Berlin-Friedrichsfelde were described using the transmission electron microscope.
      Two Sarcocystis species (Sporozoa, Sarcocystidae) were found in D. d. dama, one
      of them already known, the other new for this host. The known species was also
      found in D. dama mesopotamica. Comparing the literature, former own findings in
      roe deer, red deer or wapiti with the results reported in this paper, we conclude
      that the two Sarcocystis species should be designated as S. cf. grueneri (known
      in Dama but not named) and S. cf. hofmanni (new for Dama).

PMID- 8528306
TI  - Examination of nonflagellate and flagellate round forms of Trichomonas vaginalis
      by transmission electron microscopy.
AB  - Plasmodium-like round cells without sections of flagella, round flagellar cells
      with dividing nucleus and binuclear flagellate round forms were represented from
      the log-phase of Trichomonas vaginalis cultures. The fine-structural
      characteristics of the round cells support the opinion that the cells without
      flagella as well as the round multinuclear flagellate cells represent
      developmental stages preceding the appearance of mononuclear flagellate cells. In
      the round cells, amitotic division was observed instead of the well-known
      cryptopleuromitosis, without formation of metaphasic chromosomes and desmosomes.
      Our investigations onto the fine structure of the parasite support the assumption
      that the non-flagellate forms are viable cells of the parasite and point to still
      unknown phases of its biology.

PMID- 8528307
TI  - How do kids fit into managed care?

PMID- 8528308
TI  - Prevention push not heading off trips to the ED.

PMID- 8528309
TI  - Are doctors a dime a dozen?

PMID- 8528310
TI  - The saga of the Marshfield Clinic case.

PMID- 8528311
TI  - When the body fails, nature fills in.

PMID- 8528312
TI  - HMOs on the move. Is your town big enough for the both of you?
AB  - Health maintenance organizations are marching across the country looking for new
      territories to conquer. "They're expanding everywhere," notes one consultant. The
      winners--and losers--in this high-risk game will be determined in the next 36
      months because, as more and more consolidation takes place, the price of entry is
      becoming too expensive. So act now, because before too long it will be too late.

PMID- 8528313
TI  - A new vision of imaging.
AB  - With employers squeezing health plans and health plans squeezing providers, the
      use of expensive procedures in diagnostic imaging is tumbling. Not surprisingly,
      so is the pay of radiologists. Despite dwindling salaries, some say that
      radiology may yet emerge as a stronger, more effective discipline. Maybe, but in
      the meantime, it's become a mean time.

PMID- 8528314
TI  - Live ... and let live. When it comes to organ donations, it takes more than
      pulling heartstrings to succeed.
AB  - In the competitive world of organ procurement, Robert Hoffmann stands out--and
      not only because of his doggedness and winning record. Hoffman's low-key modus
      operandi has earned him both respect and enmity--from those who run organ
      procurement organizations and from ethicists and CEOs. What does Hoffmann know
      that you don't?

PMID- 8528315
TI  - Efficiencies. On the record.

PMID- 8528316
TI  - Quality patrol. Prescription for accuracy.

PMID- 8528317
TI  - Artwork. Capturing healers on canvas.

PMID- 8528319
TI  - Hospital pulse ... June 1995.

PMID- 8528318
TI  - Customer service. Insights from playing patient.

PMID- 8528320
TI  - Specializing. Hitting the highlights.

PMID- 8528321
TI  - Reengineering. Crafting care centers.

PMID- 8528322
TI  - Checklist. Making your community healthier.

PMID- 8528323
TI  - Painful realities.

PMID- 8528324
TI  - Continuum of care. The cost of living longer.

PMID- 8528325
TI  - Human resources ... health care companies lag behind other big businesses in
      their use of long-term financial incentives to motivate employees.

PMID- 8528326
TI  - Physicians ... primary care physicians in managed care practices still earn more
      than those in nonmanaged care practices.

PMID- 8528328
TI  - Human resources. Not whistling while they work.

PMID- 8528327
TI  - Consumers. The feminine mystique.

PMID- 8528329
TI  - Consumers ... largest consumer health survey in history.

PMID- 8528330
TI  - Payment ... new 24-hour insurance crime hot line.

PMID- 8528331
TI  - Public health. Snuffing out underage smoking.

PMID- 8528332
TI  - Faded glory. Will nursing ever be the same?
AB  - One year there seem to be too few nurses, the next too many. We insist that we
      can't get along without nurses, and then replace them with unlicensed aides while
      still holding them liable for the work those aides do. Not surprisingly, nurses
      are calling one another names and filing lawsuits. Unions are bickering.
      Associations are splintering. There have even been death threats. What's going on
      here, and will nursing ever be the same?

PMID- 8528333
TI  - Medical express ... physician practice management.
AB  - There's a hot new acronym in town, and investors from Wall Street to your street
      are paying attention. Physician management companies--better known as PMCs--are
      the newest force in the health care market. But is this bigger-is-better approach
      alienating more people than it's attracting? And how long before the boom goes
      burst?

PMID- 8528334
TI  - Behind closed doors.
AB  - Wouldn't you like to know what the executives at other health systems in your
      market are thinking--and saying--behind closed doors, as they prepare their
      strategic game plan for managed care? We certainly would, so we asked a leading
      expert in the field to re-create--docudrama style--what goes on once the
      conference doors shut and the hard work begins.

PMID- 8528335
TI  - Richard Doyle. Interview by Mark Hagland.

PMID- 8528336
TI  - Managed care. More docs to pick from.

PMID- 8528337
TI  - Reengineering. Piecing the puzzle together.

PMID- 8528338
TI  - Affiliations. Breaking up is hard to do.

PMID- 8528339
TI  - Teamwork. Primary nursing pioneers.

PMID- 8528340
TI  - Executives. Sharing insights on the inside.

PMID- 8528341
TI  - Substance abuse. A family care affair.

PMID- 8528343
TI  - Turn your focus outside-in.

PMID- 8528342
TI  - Public health. AIDS invades rural Maine.

PMID- 8528344
TI  - Feeling no pain.

PMID- 8528345
TI  - Social conscience.

PMID- 8528346
TI  - Street smarts.

PMID- 8528347
TI  - Progressively increased serum 1,25-dihydroxyvitamin D2 concentration in a
      hypoparathyroid patient with protracted hypercalcemia due to vitamin D2
      intoxication.
AB  - A 76-year-old female patient who had been taking vitamin D2 100,000 U/day for
      more than 14 years due to hypoparathyroidism following total throidectomy was
      admitted because of protracted hypercalcemia. On admission, the levels of serum
      vitamin D2 (99.8 ng/ml) and 25-OHD2 (356 ng/ml) were very high, and 1,25-(OH)2D2
      was low (4.0-18.7 pg/ml). Serum D3' 25-OHD3 and 1,25-(OH)2D3 were below the
      normal range. Despite intensive hydration with saline, intravenous
      hyperalimentation with phosphate- and calcium-free nutrients, and administration
      of glucocorticoid and calcitonin, the hypercalcemia persisted, accompanied by
      hypoproteinemia, edema, pleural effusion and congestive heart failure. The serum
      D2 and 25-OHD2 concentrations remained high and were accompanied by a gradual
      increase in 1,25-(OH)2D2 (121 pg/ml), which further increased after the
      administration of bisphosphonate (pamidronate) to 183 pg/ml. Seventeen months
      later, serum calcium and 1,25-(OH)2D2 were normalized but serum D2 and 25-OHD2
      remained high. The serum 24,25-(OH)2D2/25-OHD2 ratio was relatively constant
      throughout her clinical course, whereas the low serum 1,25-(OH)2D2/25-OHD2 ratio
      at admission gradually increased during admission, suggesting that the increase
      in serum 1,25-(OH)2D2 is due to increased production rather than decreased
      degradation. The administration of pamidronate further increased serum 1,25
      (OH)2D2. These features of the clinical course demonstrate that the 1,25
      dihydroxyvitamin D concentration in hypercalcemic patients with protracted
      vitamin D intoxication may be decreased, normal or increased. Possible factors
      responsible for a protracted increase in serum 1,25-(OH)2D2 are body weight loss,
      hypoproteinemia, and phosphate depletion. In addition, some bisphosphonates would
      certainly promote PTH-independent production of 1,25-(OH)2D2.

PMID- 8528348
TI  - A case of hyperthyroidism due to pituitary resistance to thyroid hormone.
AB  - A fifteen-year-old male was admitted to our hospital because his thyroid function
      showed a lack of TSH suppression in the face of elevated thyroid hormone. This
      patient complained of heat intolerance, palpitation and hand tremor. Peripheral
      indices of thyroid hormone action indicated a hypermetabolic state. Serum TSH did
      not respond sufficiently to TRH stimulation, suggesting TSH-secreting pituitary
      adenoma. However, sellar CT scan and MRI images did not demonstrate any pituitary
      adenoma. Moreover, the serum TSH alpha-subunit concentration was not high and
      serum TSH was partially suppressed by the administration of T3. Furthermore, the
      results of single stranded conformation polymorphism (SSCP) suggested the
      existence of mutation(s) in the exon 7 of T3 receptor beta (TR beta) gene of this
      patient. These findings support the diagnosis of pituitary resistance to thyroid
      hormone.

PMID- 8528349
TI  - The quality of life of Turner women in comparison with grown-up GH-deficient
      women.
AB  - Various aspects of the way of life in 20 adult patients (mean age: 25.7 +/- 6.0)
      with Turner syndrome were studied for their quality of life (QOL). The study
      found that many more Turner women went on to university (P < 0.01) than the
      general population, whereas GH-deficient women did not. The employment status of
      both Turner and GH-deficient women does not differ from that of the general
      population. Only 7 of the 12 Turner and 5 of the 15 GH-deficient employees are
      satisfied with their present jobs, but 10 of the former and 7 of the latter women
      think that their jobs are worthwhile. The total annual income of 3 of 19 Turner
      women exceeded 3 million yen, but not that of any of 10 GH-deficient women who
      answered the question on their income. Half of the Turner and GH-deficient women
      complained of shoulder stiffness and one fourth of the Turner and one fifth of
      the GH-deficient women have a sense of despair and irritability. Seven Turner and
      9 GH-deficient women have anxiety about their body, and 6 of the former and 8 of
      the latter have anxiety about marriage. Only 4 Turner and 3 GH-deficient women
      are married. Three of the former marriages were arranged by their parents, but
      all 3 GH-deficient women got married after falling in love. These marriage rates
      are significantly lower (P < 0.005) than that of the age-matched general
      population. Most of the unmarried women in both groups live with their parents,
      and half of the Turner and one third of the GH-deficient women have difficulty in
      getting clothes and shoes to fit them. Otherwise, they have no particular problem
      in their daily life. In conclusion, Turner women are well educated and work as
      normal women, but they, as well as GH-deficient women, appear to be anxious about
      their body and marriage.

PMID- 8528350
TI  - Histological changes in placental syncytiotrophoblasts of poorly controlled
      gestational diabetic patients.
AB  - It seems reasonable to expect that biochemical changes occurring in the pregnant
      woman with diabetes should be reflected in the placenta structure. However, it
      has not been possible to correlate placental morphology with glycemic control in
      a comparison between those with long life diabetes and poorly controlled
      gestational diabetes. In the present study we have histologically studied the
      syncytiotrophoblast of human placentae from overt diabetic and poorly controlled
      gestational diabetic patients. Using specific staining techniques and direct
      light microscopy we qualitatively studied these placentae and compared them with
      the normal placentae. We found fibrin thrombi, villous oedema, hyperplasia and
      thickening of basement membrane in the placentae of poorly controlled gestational
      diabetic mothers. Direct microscopy revealed that these various changes in
      syncytiotrophoblast structure were marked in the poorly controlled gestational
      placenta compared with overt diabetics, and could have been due to the presence
      of histochemical compounds e.g. general carbohydrates and lipids. These studies
      may indicate that poor control of diabetes during the gestation as indicated by
      high level HbAlc may result in the accummulation of carbohydrate compounds and
      fat droplets in the placental basement membrane, leading to structural changes in
      the placental cells.

PMID- 8528351
TI  - Evaluation of estrogen treatment in female patients with dementia of the
      Alzheimer type.
AB  - This study was designed to investigate the therapeutic efficacy of estrogen in
      female patients with dementia of the Alzheimer type (DAT). Fifteen DAT patients
      with a mean age of (mean +/- SE) 71.9 +/- 2.4 years were treated with 0.625 mg of
      conjugated equine estrogens orally twice a day for 6 weeks. Of the 15 DAT
      patients, 4 were diagnosed as mild, 7 as moderate and 4 as severe. The effects of
      estrogen on DAT patients were evaluated by psychometric assessments, behavior
      rating scales, regional cerebral blood flow (rCBF) measurement and quantitative
      EEG analysis. Psychometric assessments consisted of Mini-Mental State Examination
      (MMSE) and Hasegawa Dementia Scale (HDS). Dementia syndromes were evaluated by
      the GBS-Scale (GBSS) and Hamilton Depression Rating Scale (HDRS). During estrogen
      replacement therapy (ERT), the mean MMSE score (mean +/- SE) increased
      significantly from 11.6 +/- 1.9 to 13.2 +/- 2.0 at 3 weeks (P < 0.01) and 13.8 +/
      2.0 at 6 weeks (P < 0.001). The mean HDS score increased significantly from 8.6
      +/- 2.1 to 11.5 +/- 2.3 at 3 weeks (P < 0.001) and 11.6 +/- 2.6 at 6 weeks (P <
      0.01). Significant improvements in the mean scores of the GBSS and HDRS were also
      observed in the estrogen-treated group, but not in the untreated control group
      with a mean age of 71.2 +/- 2.5 years (n = 15). The rCBF was measured by single
      photon emission computed tomography (SPECT). ERT increased the mean rCBF
      significantly in the lower frontal region (P < 0.01) and primary motor area (P <
      0.02) of the right hemisphere. The mean absolute power delta band values in both
      left and right frontal EEG (Fp1 and Fp2) (P < 0.01) and theta, band values in Fp2
      (P < 0.05) decreased significantly during ERT. It is inferred that ERT
      significantly improves cognitive functions, dementia symptoms, regional cerebral
      blood flow and EEG activity in female patients with DAT.

PMID- 8528352
TI  - Two cases of asymptomatic adrenocortical insufficiency with autoimmune thyroid
      disease.
AB  - Two cases of asymptomatic adrenocortical insufficiency are reported. Both
      patients had a normal cortisol and increased ACTH. The cortisol response to ACTH
      was impaired, although not absent, in both cases. One case was associated with
      autoimmune polyglandular syndrome type II (Graves' disease and vitiligo), and the
      other was possibly associated with an early stage of Hashimoto's thyroiditis,
      suggesting autoimmune pathogenesis of their adrenocortical insufficiency. CT of
      the abdomen revealed unilateral enlargement of the adrenal glands in one case,
      but no enlargement of the adrenal glands in another case. Adrenal hypofunction
      seemed to be compensated for by increased trophic hormone (ACTH), as in
      subclinical hypothyroidism. However, prolonged ACTH stimulation increased urinary
      17-OHCS in both cases, and normalized cortisol response to ACTH in one case. In
      both cases, the plasma renin activity (PRA) and plasma aldosterone concentration
      (PAC) were normal, and adrenal autoantibodies were negative, suggesting that
      neither negative adrenal autoantibodies nor normal PRA can exclude asymptomatic
      adrenocortical insufficiency. The results suggest that a rapid ACTH test should
      be performed in cases with increased ACTH, especially those associated with other
      autoimmune endocrine disorders.

PMID- 8528353
TI  - Comprehensive adrenocortical steroid measurements in two cases of Schmidt's
      syndrome.
AB  - We treated two patients with Schmidt's syndrome who showed some differences in
      the endocrinological findings in adrenal steroidogenesis. However, there had been
      no reports describing in detail which zone(s) is most usually destroyed in the
      adrenals in Schmidt's syndrome of which the pathogenesis is thought to be
      intimately related to immunological disturbances. Case 1 is a 63-year-old female,
      presenting a complete deficiency of almost all adrenal steroids. Case 2 is a 53
      year-old female, showing a partial deficiency of adrenal steroids, and
      examination of various plasma adrenal steroids suggests that impairment of the
      zona fasciculata may be mainly confined to the adrenal cortex. The results of
      aspiration biopsy cytology of the thyroid demonstrated the presence of chronic
      thyroiditis in each case. Case 2 also presented empty sella detected by MRI of
      the pituitary gland. It is therefore suggested that zona fasciculata cells may be
      first destroyed and the impairment seems to spread to all zones in the adrenals
      in Schmidt's syndrome. Moreover, some patients with Schmidt's syndrome may have
      empty sella.

PMID- 8528354
TI  - A cDNA encoding a new member of the rat placental lactogen family, PL-I mosaic
      (PL-Im).
AB  - We have isolated a cDNA encoding a novel placental lactogen (PL), PL-I mosaic (PL
      Im), by screening the cDNA library in lambda ZAP of the mid-pregnant (day 12) rat
      placenta. The cDNA comprised an open reading frame of 687 bp encoding 229 amino
      acids, in which there were two putative N-glycosylation sites. Northern blot
      analysis showed that PL-Im mRNA was expressed specifically during mid-pregnancy
      (days 10 and 12) in the rat placenta. The cDNA was highly homologous with those
      of other rat PL family members; in particular, the homology among PL-Im, PL-I
      (mid-pregnancy-specific) and PL-Iv (late-pregnancy-specific) was over 90%.
      Interestingly, the nucleotide sequence of PL-Im cDNA was a mosaic of PL-I and PL
      Iv and it did not possess its own particular sequence. As the genomic pattern
      determined using Southern blot analysis of PL-Im was distinct from that of PL-I
      and PL-Iv, the encoded area of PL-Im appears to be independent of those of PL-I
      and PL-Iv on the gene. In the dendrogram of the rat PL family constructed on the
      basis of the nucleotide sequence homologies, PL-Im was located between PL-Iv and
      PL-I in the process of molecular evolution. Therefore, PL-Im has a unique cDNA
      structure and may be a principal factor in the molecular evolution of PLs.

PMID- 8528355
TI  - Growth regulation of the human papillary thyroid cancer cell line by protein
      tyrosine kinase and cAMP-dependent protein kinase.
AB  - We established a cell line (hPTC) from the tissue of papillary thyroid cancer
      surgically excised from a 27-year-old female patient. Synthesis of cAMP by the
      hPTC cells was stimulated by TSH. This cell line has continued to divide as a
      monolayer in a tissue culture for three years. We assessed growth regulation of
      the hPTC cells by protein tyrosine kinase and cAMP-dependent protein kinase by
      measuring the DNA content of the hPTC cells in 24-well plates with 3,5
      diaminobenzoic acid after incubation in various growth factors. Basic fibroblast
      growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth
      factor-1 (IGF-1), all of which bind to their respective receptors with tyrosine
      kinase activity, stimulated DNA synthesis in the hPTC cells. Neutralizing
      antibodies to basic FGF and EGF suppressed the growth stimulation by basic FGF
      and EGF, respectively. Genistein, a specific protein tyrosine kinase inhibitor,
      inhibited proliferation of the hPTC cells. On the other hand, thyrotropin,
      dibutyryl cAMP (dBC) and forskolin inhibited proliferation. KT5720, a specific
      cAMP-dependent protein kinase inhibitor, restored the growth of the hPTC cells
      even in the presence of dBC. This study shows that stimulation of the protein
      tyrosine kinase activity by basic FGF, EGF, and IGF-1 promoted DNA replication by
      the human thyroid cancer cell line. However, activation of the cAMP-dependent
      protein kinase inhibited proliferation of this cell line.

PMID- 8528356
TI  - Serum immunoreactive inhibin levels in polycystic ovarian disease (PCOD) and
      hypogonadotropic amenorrhea.
AB  - To evaluate the physiological significance of inhibin in various types of
      amenorrhea, serum immunoreactive (IR)-inhibin levels were measured and compared
      with those in normal cycling women. Amenorrheic women were as follows: (1) 23
      women with PCOD, 11 women with hypogonadotropic amenorrhea (HA, n = 23) and 11
      women with regular menstrual cycles. Women with HA were further divided into 2
      groups according to the presence or absence of withdrawal bleeding (WDB) after
      progesterone administration. HA with WDB was categorized as HA1, while HA without
      as HA 2. Serum IR-inhibin levels in women with PCOD were significantly higher
      than those in HA 2 and normal women at days 2 to 5 from the onset of menstruation
      and significantly lower than those in normal women in the mid-luteal phase. A
      significant positive correlation was obtained between IR-inhibin and FSH in HA 2
      (r = 0.681) and HA 1 (r = 0.658), but no significant correlation between these
      two hormones in PCOD and normal women. These results indicated that basal IR
      inhibin levels vary with types of amenorrhea. High IR-inhibin levels in PCOD
      patients suggest that inhibin plays a part in the discordant gonadotropin
      secretion in these patients.

PMID- 8528357
TI  - Effect of GnRH antagonists on phorbol ester-induced LH release from rat pituitary
      gonadotrophs.
AB  - We previously reported that a blockade of GnRH receptor activation inhibited the
      already-initiated C-kinase pathway(s). We tried to investigate whether this
      finding is a general phenomenon or not. In this study, we employed three GnRH
      antagonists, [D-Phe2,Pro3,D-Phe6]-GnRH, [Ac-D-Nal-Ala1,D-pCl-Phe2,D-Ser(Rha)6]
      GnRH, and [Ac-D-p-Cl-Phe1,2,D-Trp3,D-Lys6,D-Ala10]-GnRH (referred to as #1-, #2-,
      #3-GnRH antag., respectively). Each antagonist was examined for its potency
      against GnRH by analyzing its inhibitory effect on LH release from pituitary
      gonadotrophs as well as on the increase in the cytosolic Ca2+ concentration. As a
      result, the #1-GnRH antag. was found to be weaker than the other two compounds.
      Consistent with a previous study, the #3-GnRH antag. inhibited the action of TPA
      on LH release. However, independently of their potency as GnRH-antagonists, the
      two other antagonists had no inhibitory effect on TPA-induced LH release. While
      it is generally accepted that the C kinase pathway plays a major role in the GnRH
      induced LH release, not all GnRH antagonists can inhibit LH release by blocking
      the already-activated C kinase system.

PMID- 8528358
TI  - Biochemical significance of 19-hydroxytestosterone in the process of
      aromatization in human corpus luteum.
AB  - 19-Hydroxyandrogens are known to be an intermediary metabolite in the aromatizing
      reaction, though the physiological role of this compound has not yet been
      clarified. In this study, microsomes obtained from human corpus luteum were
      incubated with testosterone or 19-hydroxytestosterone (19-OHT) as the substrate
      to investigate the biochemical significance of 19-OHT in the process of
      aromatization in the ovary. The inhibitory effects of 4-hydroxyandrostenedione (4
      OHA) on the formation of estradiol from testosterone and 19-OHT in human ovary
      were also investigated. When testosterone was incubated with human ovarian
      microsomes, 19-OHT and estradiol were identified. When 19-OHT was used as the
      substrate, the formation of estradiol was demonstrated. To our knowledge, this is
      the first report to demonstrate the formation of estradiol from 19-OHT in human
      ovarian tissue. The Km value of aromatase for testosterone on human corpus luteum
      microsomes was 0.21 microM. 4-OHA exhibited inhibition with a Ki of 35 nM. With
      testosterone and 19-OHT as the substrate, the formation of estradiol was also
      equally inhibited by 4-OHA. A dose dependent inhibition of estradiol formation
      was observed, with no apparent accumulation of 19-OHT. These results suggest that
      19-OHT may not only be an intermediary metabolite in the aromatization of
      testosterone by human ovary but could be a product of the microsomal enzyme.

PMID- 8528359
TI  - Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular
      hyperplasia: a case report and immunohistochemical studies.
AB  - A 55-year-old woman developed Cushing's syndrome due to ACTH-independent
      bilateral adrenocortical macronodular hyperplasia. Plasma ACTH was undetectable,
      and was not stimulated by administration of metyrapone, CRH, or insulin.
      Hypercortisolism was not suppressed by a high dose of dexamethasone, but was
      responsive to ACTH. Both adrenal glands were enlarged with a total weight of 200
      g, and contained multiple nodules composed of two cell types (large clear cells
      and small compact cells). In immunohistochemical studies, P450c17
      immunoreactivity was predominantly observed in small compact cortical cells,
      while that of 3 beta HSD was observed exclusively in large clear cortical cells.
      This pattern of expression of steroidogenic enzymes as well as histological and
      clinical features is considered to be unique to ACTH-independent bilateral
      adrenocortical macronodular hyperplasia.

PMID- 8528360
TI  - Octreotide treatment results in the inhibition of GH gene expression in the
      adenoma of the patients with acromegaly.
AB  - Seven patients with growth hormone (GH)-secreting pituitary adenoma were treated
      preoperatively with octreotide (Sandostatin or SMS 201-995; a somatostatin
      analogue), and were compared with 18 non-treated patients in their clinical
      courses and adenoma analyses. Octreotide treatment improved the endocrinological
      data in all 7 cases. The octreotide-treated adenomas were soft and easily removed
      by suction and curettage. The postoperative normalization of endocrinological
      data was encountered more often in the octreotide-treated cases than in the non
      treated, although the statistical significance was not observed by the limited
      number of cases. The adenoma tissues were examined with conventional histology
      and immunohistochemistry, and the amount of GH messenger ribonucleic acid (mRNA)
      was quantitatively assessed. The studies demonstrated: 1) No fibrosis nor
      necrosis was observed in the adenomas from the octreotide-treated patients. 2)
      Immunohistochemistry for human GH revealed no remarkable differences between the
      octreotide-treated and the non-treated adenomas. 3) The amounts of GH mRNA in the
      adenoma from the octreotide-treated patients were 4.2 +/- 1.8 (mean +/- SEM;
      expressed in an arbitrary unit) and were significantly less than those from the
      non-treated (33.6 +/- 9.1). These data suggest that octreotide inhibits not only
      GH release from the adenoma but also its biosynthesis.

PMID- 8528361
TI  - Antiandrogenic activity and endocrinological profile of a novel antiandrogen, TZP
      4238, in the rat.
AB  - TZP-4238 is a new potent, orally active steroidal antiandrogen. Antiandrogenic
      activity and endocrinological profile of TZP-4238 were investigated in rats,
      except that progestational activity was determined in rabbits. TZP-4238
      suppressed the testosterone propionate-induced increases in the weights of the
      ventral prostate, seminal vesicle and levator ani in castrated immature male
      rats. TZP-4238 also decreased the weights of the ventral prostate, seminal
      vesicle and levator ani in intact adult male rats, but did not affect the weight
      of the testis or the serum concentrations of luteinizing hormone and
      testosterone. TZP-4238 did not have such an inhibitory effect on the weight of
      the adrenal gland as seen in other steroidal antiandrogens. It exhibited potent
      progestational activity. Although TZP-4238 did not exert androgenic or estrogenic
      activity, it had weak antiestrogenic activity. These results suggest that TZP
      4238 exerts an antiandrogenic effect on the prostate without any compensatory
      change in the serum concentration of luteinizing hormone or testosterone in rats,
      and it is a useful drug for the treatment of androgen-dependent diseases such as
      prostatic hypertrophy and prostatic cancer.

PMID- 8528362
TI  - Plasma CRH response to water immersion-restraint stress in rats bearing a
      hypothalamic knife cut.
AB  - We reported earlier that the plasma level of corticotropin-releasing hormone
      (CRH) remained high 120 min after the onset of such strong sustained stress as
      ether-laparotomy or water immersion-restraint, which reflected the persistent
      secretion of CRH from the hypothalamic median eminence (ME). We investigated the
      change in plasma CRH during water immersion-restraint stress in rats bearing an
      anterolateral cut around the medial basal hypothalamus (MBH) which cuts the CRH
      neurons from the PVN to the ME. Concentrations of CRH in the hypothalamus,
      extrahypothalamic tissues and peripheral blood were measured by radioimmunoassay.
      Plasma ACTH was measured with an immunoradiometric assay kit. Plasma baseline
      ACTH and CRH concentrations did not differ significantly in the sham vs. cut
      groups. At 120 min after the onset of stress, plasma ACTH concentrations were
      definitely higher in both groups. In the cut group, plasma CRH at 120 min after
      stress did not differ significantly from the baseline level, whereas plasma CRH
      at 120 min was definitely higher in the sham group. Baseline CRH concentrations
      in the ME did not differ greatly in the two groups. CRH concentrations in the ME
      of both groups had decreased appreciably 120 min after the onset of stress as
      compared with baseline CRH, and the CRH decrease was greater in the cut group
      than in the sham group. CRH in the neurointermediate lobe (NIL) and adrenal gland
      of both groups showed no significant change at 120 min, compared with the
      control. These findings confirm that the continuous CRH increase in plasma during
      sustained stress is derived mainly from the hypothalamus.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8528363
TI  - Cushing's disease associated with adrenal myelolipoma, adrenal calcification and
      thyroid cancer.
AB  - A 51-year-old woman with Cushing's disease associated with adrenal myelolipoma is
      reported. A further characteristic feature was the coexistence of bilateral
      adrenal calcification and thyroid cancer. Previously several cases of adrenal
      myelolipoma associated with endocrine dysfunction were reported. The combination
      of Cushing's disease and adrenal myelolipoma has only been described in two cases
      of recurrent Cushing's disease but never in an initial occurrence of Cushing's
      disease. Continued stimulation by excessive adrenocorticotropic hormone (ACTH)
      not only developed adrenal hyperplasia but also might be involved in the
      pathogenesis of adrenal myelolipoma.

PMID- 8528364
TI  - A family with hereditary high serum thyroxine-binding globulin.
AB  - A family with hereditary high serum thyroxine-binding globulin was studied. All
      the subjects studied were clinically euthyroid without goiter. The propositus
      (female), her mother and sister had high TBG, total T4 and total T3 with normal
      free T4, free T3 and TSH. Her father's thyroid function was within the normal
      range. Possible etiologic factors causing secondary hyper-TBG-nemia were ruled
      out in all the affected subjects. Isoelectric focusing demonstrated qualitatively
      normal microheterogeneity, ruling out possible TBG variations caused by liver
      diseases, estrogen therapy or pregnancy. Although the mechanism involved in the
      TBG increase awaits further investigation, it could be an abnormality in the gene
      controlling the synthesis of TBG.

PMID- 8528365
TI  - Cryptosporidium in water supplies: the second Badenoch report.

PMID- 8528366
TI  - AIDS and HIV-1 infection worldwide.

PMID- 8528367
TI  - Invasive meningococcal disease and influenza.

PMID- 8528368
TI  - Update on invasive meningococcal infections.

PMID- 8528369
TI  - Tetraethylammonium-induced calcium concentration changes in skin fibroblasts from
      patients with Alzheimer disease.
AB  - Potassium (K+) channel dysfunction in fibroblasts was recently proposed as a
      potential diagnostic marker for Alzheimer disease (AD). We utilized a
      microspectrofluorometric method with Fura-2AM to measure intracellular free
      calcium ([Ca2+]i) following depolarization with the K+ channel blocker
      tetraethylammonium (TEA) in seven AD and seven control fibroblast cultures.
      Contrary to our expectation, 43% of the AD and 36% of the control fibroblast
      plated coverglasses responded with an increase in [Ca2+]i on addition of 100 mM
      TEA. The data suggest that the TEA-elicited [Ca2+]i response is not a useful AD
      screening test.

PMID- 8528370
TI  - Long-term effects of tacrine on regional cerebral blood flow changes in
      Alzheimer's disease.
AB  - Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's
      disease (AD) before and after 14 months of tacrine treatment. The treated group
      was compared with an identical reference group of untreated AD patients. At
      baseline the two groups showed an identical rCBF and mean hemispheric blood flow.
      After 14 months the tacrine-treated patients showed a stable rCBF level and a
      significant increase in rCBF in the central-parietal regions, compared to the
      untreated reference group, who showed typical AD reductions in rCBF in these
      regions. CLINICAL OUTCOME: 7 of 9 patients in the tacrine group were clinically
      unchanged or slightly improved during the study time. In the untreated group 8 of
      11 patients had deteriorated in clinical assessments and none had improved. Long
      term tacrine treatment in Alzheimer's disease may delay the progression of
      symptoms.

PMID- 8528371
TI  - Changes of the relative severity of naming, fluency and recall impairment in the
      course of dementia of the Alzheimer type.
AB  - In a longitudinal study of 90 patients with mild to moderate dementia of the
      Alzheimer type (DAT) we investigated the relative severity of impairment in a
      confrontation naming, a categorical word fluency and a word list recall task.
      Severity of impairment was assessed in comparison to a healthy age-matched
      control group. At baseline, confrontation naming and fluency deficits were about
      equally often the most severe deficit. The number of patients with most severe
      naming deficits increased from mild to moderate dementia and from baseline to 1
      year follow-up. Word recall was the most severe deficit only in a minority of
      patients. An addition of lexical-semantic and visual-perceptive dysfunctions is
      discussed as a possible cause for the shift towards naming deficits in the course
      of the disease.

PMID- 8528372
TI  - Effect of seizures on progression of dementia of the Alzheimer type.
AB  - A survey of institutionalized patients with clinical diagnosis of probable
      dementia of the Alzheimer type (DAT) indicated that 21% of patients developed
      seizures after the onset of DAT. Of the total of 27 patients, 11 developed
      seizures at home and 16 after institutionalization. In 9 of 11 patients (82%),
      who suffered the initial seizure at home, the patients' condition suddenly
      worsened and required long-term care admission within 6 months of the seizure
      onset. Language function declined significantly more rapidly in 5 patients with
      seizures than in controls matched by age and duration of DAT.

PMID- 8528373
TI  - Eye movement dysfunction in dementia of the Alzheimer type.
AB  - Patients with dementia of the Alzheimer type (DAT) are described to have
      disturbances in basic visual, complex visual and oculomotor functions. In order
      to study and quantify dysfunction of eye movements under several paradigms, they
      were measured with infrared photoelectric techniques and analyzed by a digital
      computer. The study included 12 normal subjects and 10 patients with mild to
      moderate DAT (DSM-III-R criteria). The authors' results could demonstrate both an
      attentional deficit to externally triggered, unpredictable targets and an
      impaired systematic, voluntary, internally organized scanning of the environment
      due to motivational and perceptional deficits.

PMID- 8528374
TI  - Temporal quantification of Alzheimer's disease severity: 'time index' model.
AB  - A fundamental issue in the clinical and neuropathological assessment of
      Alzheimer's disease patients is quantification of dementia severity progression.
      Several methods have been advanced for the purpose of staging dementia with
      various sensitivities at different phases of the disease, but no mathematical
      function has been developed to link these measures to a physical continuum. Using
      a dynamic method for quantifying illness severity, change in severity over time
      was referenced to a cumulative temporal index, a physical dimension. Data from 33
      patients with probable Alzheimer's disease with at least 2 successive assessments
      on three 50-point scales measuring cognitive, behavioral, and daily living skills
      were used to determine rate of change. 'Fuzzylogic' smoothing of the data,
      integration over time, and least-squares regression were used to derive a cubic
      polynomial function to calculate a severity measure in which 'days of illness'
      was estimated from the severity score. This method can be used to improve the
      comparability of performance across various mental status tests, and to link
      measures of very early phases of preclinical dementia and late profound dementia
      phases. This method also provides a description of an 'average' time course for
      any population from which the index is derived.

PMID- 8528375
TI  - Changes in a CSF antigen associated with dementia.
AB  - An 85-kDa antigen was detected in cerebrospinal fluid (CSF) using a monoclonal
      antibody, 11.57, raised against a fraction of paired helical filaments extracted
      from Alzheimer's disease (AD) brain tissues. The antigen is a thermostable
      protein that is unrelated either to tau or amyloid beta-protein precursor. Its
      level was measured in lumbar and post-mortem CSF samples and found to be
      decreased significantly in patients with dementia as compared with non-demented
      controls. There was no difference in its level between patients with AD and those
      with non-Alzheimer type dementia. In AD, however, there was a significant
      relationship between disease progression and the amount of the 85-kDa antigen.

PMID- 8528376
TI  - Intravascular malignant lymphomatosis: a cause of subacute dementia.
AB  - Intravascular malignant lymphomatosis (IML) is a rare disease characterized by
      proliferation of neoplastic cells of lymphoid origin within small blood vessels.
      The median survival of IML patients is only 6 months. Any organ can be affected,
      with or without clinical expression. Although skin lesions are classic, they are
      relatively uncommon (28%). Neurological symptomatology (which evolves over a few
      weeks) is the most common clinical expression (83%). Dementia is the most common
      neurological symptom that occurs in about half of the patients with central
      nervous system pathology, and is associated with poorer prognosis. The diagnosis
      is confirmed by histology but, except for lung, biopsies are not sensitive and
      are helpful only when performed in the symptomatic organs; furthermore, when
      associated with anesthesia, they can be followed by dramatic worsening of the
      patient's condition. Elevated LDH is a good indicator of IML in patients with
      subacute neurological symptomatology, especially if associated with signs
      suggestive of other organ involvement.

PMID- 8528377
TI  - A case of Alzheimer's disease with extensive focal white matter changes.
AB  - The case of a patient is reported who suffered from disturbed concentration and
      memory and constructive apraxia. She had only mild neuropsychological deficits at
      the first examination. T2-weighted MRI presented extensive focal white matter
      changes. A brain biopsy showed changes typical for Alzheimer's disease (AD). The
      extent of the white matter lesions was surprising compared to the mild clinical
      signs she had. This case confirms that AD may result in prominent white matter
      disease caused by incomplete infarction or demyelination.

PMID- 8528378
TI  - Factors associated with pain complaints in a clinical sample of postmenopausal
      women.
AB  - The aims of this study were to evaluate the relationships occurring between pain
      complaints and postmenopausal status, and to look at the correlation between such
      complaints and other symptoms commonly related to the climacterium. A clinical
      sample of 99 consecutive postmenopausal patients requiring medical help were
      studied: 36 complained of muscle-skeletal pains whereas 33 presented with
      headache limiting daily activity. Climacteric syndrome, level of distress, coping
      style and bone mineral density were assessed with appropriate questionnaires and
      instruments. Neither bone mineral density, nor body mass index nor time since
      menopause were associated with either headaches or muscle-skeletal pains.
      According to the logistic regression being younger, being without a job,
      suffering from insomnia and having a lower ability in self-support by the means
      of comforting ideas predicts suffering from headache. A high level of distress
      and an avoidance behavior to problem facing predict the presence of pain
      complaints. In such cases the ineffectiveness of the coping mechanism (i.e. avoid
      the problem) could be the reason for the increased level of psychological
      distress. These findings indicate that complaining of pains or headache is not
      dependent upon postmenopausal status. Individual coping strategies and their
      effectiveness seem the main reasons for the presence of disabling musculoskeletal
      pains or headache.

PMID- 8528380
TI  - Involuntarily childless couples: their desire to have children and their motives.
AB  - Long-term infertile couples often reflect seriously on their desire for a child.
      By investigating involuntarily childless couples we might get a better
      understanding of the intensity of the desire for the first child, the motives
      behind this desire and the difference between men and women in these respects. In
      this study among 108 couples with a mean infertility period of 8.6 years, the
      desire for children was still very strong especially among the women. Also, there
      were differences between men and women as to their motives for having a child.
      The most frequent motives for wanting a child are part of the categories
      happiness and well-being. Motives within the categories social control and
      continuity were seldom mentioned. Among women with the most intense desire for a
      child, motives within the categories motherhood and identity-development were
      very important.

PMID- 8528379
TI  - The abortion decision: reasons and ambivalence.
AB  - Self-in-relation theory and pilot data responses to an Abortion Decision Balance
      Sheet by 20 women attending an abortion-providing clinic challenge previous
      formulations of the abortion decision. Pilot data suggest that: women may make an
      abortion decision based primarily on pragmatics, a belief in their right to
      choose and knowledge of the safety and simplicity of the procedure. A discrepancy
      may exist for a significant minority of women between their abstract
      beliefs/knowledge and the personal meaning for them of the pregnancy, abortion
      and its safety. Important links may exist between maternal attachment and anxiety
      about the safety of the abortion procedure. Ramifications for counselling and
      future research are discussed.

PMID- 8528381
TI  - Premenstrual tension among hysterectomized women.
AB  - What is the prevalence of premenstrual tension (PMT) among women who have no
      uterus? Three hundred and seventeen hysterectomized women aged 28-45 years, were
      asked to describe their health before and after surgery. Most of the women (88%)
      felt that their general health improved postoperatively. There was a significant
      reduction in the percentage of women reporting moderate to severe PMT in all or
      almost all cycles: pre- versus post-hysterectomy, 56.1 versus 18.9; p < 0.001. Of
      the 178 women who considered PMT to have been a regular feature of their
      prehysterectomy menstrual cycles, 73% either lost their symptoms after surgery or
      felt that they were now minimal. It is concluded that the prevalence of PMT among
      hysterectomized women is low compared with that among women who have a uterus.

PMID- 8528382
TI  - Experiences of the male partner in cervical and endometrial cancer--a prospective
      interview study.
AB  - This article focuses on social, psychological and sexual experiences of 47 men
      before their partner was treated for cervical or endometrial cancer and 1 year
      later. As a complement to the interviews the men completed a symptom check-list.
      Before initiation of treatment, a great majority of the men were in psychological
      crisis. The number of psychological symptoms decreased from the first to the last
      interview. Symptoms with psychosomatic character increased, however,
      considerably. In the endometrial group, several had intrapsychic problems, while
      interpersonal problems were more common in the cervical group. Both groups found
      it difficult to know how to behave and how to communicate with their partner,
      friends and acquaintances. A majority had nobody to whom they could speak
      honestly, and most did not obtain basic information about their partner's
      disease. The experiences of intercourse were much more negative after completed
      treatment and a majority described impaired sexual desire. Provided that the
      woman herself desires it, the coping and rehabilitation of the woman, the man and
      the couple would improve if the male were integrated in the care program from the
      moment the diagnosis of cancer is made.

PMID- 8528383
TI  - Factors associated with mothers selecting general anesthesia for lower segment
      caesarean section.
AB  - The objective of the study was to investigate the sociodemographic and
      psychological factors which are associated with choice or refusal of regional
      anesthesia for lower segment Caesarean section. A semi-structured questionnaire
      was administered preoperatively to consecutive women presenting for elective
      operation at two hospital sites in the same health authority. The questionnaires
      were administered to 39 pregnant women by two anesthetists, one at each site.
      Sociodemographic and past and present obstetric and anesthetic details were
      obtained. The Hospital Anxiety and Depression scale and the FEAR questionnaire
      were used with an additional visual analog scale to assess fearfulness associated
      with the proposed operation. A 'panic checklist' of ten items was also
      constructed to identify procedures associated with feelings of panic. Ten women
      requested general anesthesia. These women had a similar level of anxiety to the
      others, but were significantly more depressed, had had more pregnancies overall
      and more without live babies. There were also more aspects of the procedure at
      which they thought they might panic. Women who have suffered the loss of a
      conception with its associated grief and often obstetric intervention are more
      reluctant to be conscious during an operative delivery for a subsequent baby.
      Preventive measures should be considered at the time of fetal loss to avoid this.
      However, preoperatively a simple visual analog scale for fearfulness would
      identify these women so that any unresolved fears could receive full
      psychological assessment.

PMID- 8528384
TI  - Electrotransformation of Chinese hamster ovary cells.

PMID- 8528385
TI  - Electroporation of rat pituitary cells.

PMID- 8528386
TI  - Electroporation of plasmid DNA into normal human fibroblasts.

PMID- 8528387
TI  - Electroporation-mediated gene transfer into hepatocytes.

PMID- 8528388
TI  - Electroporation of human lymphoblastoid cells.

PMID- 8528389
TI  - The use of electroporated bovine spermatozoa to transfer foreign DNA into
      oocytes.

PMID- 8528390
TI  - Electroporation of embryonic stem cells for generating transgenic mice and
      studying in vitro differentiation.

PMID- 8528391
TI  - Electrotransfection with "intracellular" buffer.

PMID- 8528392
TI  - Effect of cis-located human satellite DNA on electroporation efficiency.

PMID- 8528393
TI  - Quantitation of transient gene expression.

PMID- 8528395
TI  - Electroporation of Drosophila embryos.

PMID- 8528394
TI  - Stable integration of vectors at high copy number for high-level expression in
      animal cells.

PMID- 8528396
TI  - Transformation of fish cells and embryos.

PMID- 8528397
TI  - Electroporation of cardiac cells.

PMID- 8528398
TI  - Electroporation for gene therapy.

PMID- 8528399
TI  - Electrofusion of mammalian cells.

PMID- 8528400
TI  - Effects of pulse length and strength on electroporation efficiency.

PMID- 8528401
TI  - Stabilizing antibody secretion of human Epstein Barr virus-activated B
      lymphocytes with hybridoma formation by electrofusion.

PMID- 8528402
TI  - Electroporation theory. Concepts and mechanisms.

PMID- 8528403
TI  - Electrofusion of mammalian oocytes and embryonic cells.

PMID- 8528404
TI  - Nuclear transfer in bovine embryos.

PMID- 8528405
TI  - Electrofusion of mouse embryos to produce tetraploids.

PMID- 8528406
TI  - Spectrofluorometric assay for cell-tissue electrofusion.

PMID- 8528407
TI  - Cytometric detection and quantitation of cell-cell electrofusion products.

PMID- 8528408
TI  - Instrumentation.

PMID- 8528409
TI  - The introduction of proteins into mammalian cells by electroporation.

PMID- 8528410
TI  - Electroporation of antigen-presenting cells for T-cell recognition and cytotoxic
      T-lymphocyte priming.

PMID- 8528411
TI  - Electroporation of antibodies into mammalian cells.

PMID- 8528412
TI  - Electroporation of adherent cells in situ for the introduction of nonpermeant
      molecules.

PMID- 8528413
TI  - Electroporation of Brassica.

PMID- 8528414
TI  - Transformation of maize by electroporation of embryos.

PMID- 8528415
TI  - Transient gene expression analysis in electroporated maize protoplasts.

PMID- 8528416
TI  - Reporter genes and transient assays for plants.

PMID- 8528417
TI  - Electrofusion of plant protoplasts. Selection and screening for somatic hybrids
      of Nicotiana.

PMID- 8528418
TI  - Protoplast electrofusion and regeneration in potato.

PMID- 8528419
TI  - Polymer-supported electrofusion of protoplasts. A novel method and a synergistic
      effect.

PMID- 8528420
TI  - Effects of pulse length and strength on electroporation efficiency.

PMID- 8528421
TI  - Electroporation theory. Concepts and mechanisms.
AB  - The basic features of electrical and mechanical behavior of electroporated cell
      membranes are reasonably well established experimentally. Overall, the electrical
      and mechanical features of electroporation are consistent with a transient
      aqueous pore hypothesis, and several features, such as membrane rupture and
      reversible electrical breakdown, are reasonably well described quantitatively.
      This gives confidence that "electroporation" is an attractive hypothesis, and
      that the appearance of temporary pores owing to the simultaneous contributions of
      thermal fluctuations ("kT energy") and an elevated transmembrane voltage
      ("electric field energy") is the microscopic basis of electroporation.

PMID- 8528422
TI  - Instrumentation.

PMID- 8528423
TI  - Electroporation of Agrobacterium tumefaciens.

PMID- 8528424
TI  - Electroporation of DNA into the unicellular green alga Chlamydomonas reinhardtii.

PMID- 8528425
TI  - Pollen electrotransformation in tobacco.

PMID- 8528426
TI  - Electroporation of tobacco leaf protoplasts using plasmid DNA or total genomic
      DNA.

PMID- 8528427
TI  - On the need for evidence-based medicine.

PMID- 8528428
TI  - The use of condition specific outcome measures in economic appraisal.
AB  - Despite growing concern over the use of health utility measures in economic
      evaluations of health care programmes, economists have been reluctant to use the
      wealth of knowledge contained within studies using condition specific outcome
      measures (CSOMs). Problems with the measurement properties of many CSOMs means
      that the scope for their use in economic appraisal is extremely limited. This
      paper examines the potential uses of CSOMs in economics, namely: to provide valid
      descriptive material, to provide scales for comparing the effectiveness of
      interventions and to 'validate' the descriptive accuracy of economic measures of
      benefit. It is argued that valid descriptive information is essential for
      economic appraisal, no matter which method of evaluation is used. Generic
      measures have been criticised for being too narrow and insensitive to the
      consequences of specific conditions. CSOMs offer a rich source of information to
      produce quality adjusted life years (QALYs) but two potential methods, one of
      mapping health states from one scale to a QALY classification (such as Rosser),
      and the other, developing 'exchange rates' between scales are unsatisfactory. A
      more rigorous approach would necessitate a major research programme of revaluing
      existing CSOMs using preference based methods. Another interesting avenue of
      research would be to use the information from CSOMs to construct health scenarios
      for valuation. Given the current state of development of outcome measures, it
      seems advisable to use CSOMs alongside economic measures in trials. Such a
      strategy would help demonstrate the usefulness of economic measures to clinicians
      and to reconcile the two measures.

PMID- 8528429
TI  - Costing neonatal care alongside the Collaborative ECMO trial: how much primary
      research is required?
AB  - Researchers working on economic evaluations alongside trials have to balance
      minimising data collection with maximising the ability to measure differences in
      costs. Using existing data sources may keep the costs of research down, but these
      data may not be entirely appropriate to the evaluation question. When evaluating
      technologies in intensive care it is particularly important to be able to
      classify patients correctly by their resource requirements especially when those
      requirements vary considerably from day to day. This paper describes and
      justifies methods for costing the care provided for babies in (one arm of) an on
      going multi-centre trial, the Collaborative ECMO trial. This trial is evaluating
      alternative policies of life support for mature (full term) newborn babies with
      severe respiratory failure. The most reliable cost information on neonatal
      intensive care is available from a study, conducted independently from the trial,
      which has used simple cost apportionment on a large sample of units. By drawing
      on clinical opinion and carrying out a case note exercise we assessed whether
      this available information was appropriate to estimate 'baseline' costs for the
      control group during their initial 'acute' phase of illness. We concluded that
      the available cost estimates would need to be weighted to reflect the additional
      costs of drugs and investigations for this group of babies during the acute
      phase. Multidisciplinary collaboration on trials can help economists and other
      researchers to balance the requirement for simple cost measurements with more
      detailed primary research.

PMID- 8528430
TI  - Cost-effectiveness analysis of alternative treatments of African gambiense
      trypanosomiasis in Uganda.
AB  - African trypanosomiasis, or sleeping sickness, is a tropical disease caused by
      trypanosome parasites transmitted by tsetse flies. The focus of this paper is on
      the cost-effectiveness of alternative drug treatments for patients in the late
      stage of the disease. Melarsoprol has been used for many decades. More recently,
      eflornithine has been developed. It has fewer side effects and improves the
      overall cure rate. It is much more expensive than melarsoprol, however. The
      objective of the present cost-effectiveness is to identify the costs and benefits
      that would be involved in switching from melarsoprol to eflornithine in the
      treatment of late stage sleeping sickness. Benefits are expressed in lives saved
      as well as in disability adjusted life years (DALYs). The analysis is applied to
      the case of Uganda. The implications for affordability are also considered, by
      taking account of how the treatment costs would be shared between the national
      government, donors and patients. The baseline results indicate that melarsoprol
      treatment is associated with an incremental cost per life and DALY saved of $209
      and $8, respectively. Each additional life saved by switching from melarsoprol
      alone to a combination of melarsoprol and eflornithine would cost an extra $1,033
      per life saved, and an extra $40.9 per DALY gained. Shifting from this second
      alternative to treatment of all patients with eflornithine leads to an
      incremental cost per life saved of $4,444 and an incremental cost of $166.8 per
      DALY gained.

PMID- 8528431
TI  - Time preference, duration and health state valuations.
AB  - There is increasing interest in health status measurement and the relative
      weights that people attach to different states of health and illness. One
      important issue which has been raised is the effect that the time spent in a
      health state may have on the way that state is perceived. Previous studies have
      suggested that the worse a state is, the more intolerable it becomes as it lasts
      longer. However, for most of these studies, it is impossible to determine how
      much of what was observed is attributable to the time spent in the state and how
      much is attributable to when it was occurring. This paper reports on a pilot
      study designed to test the feasibility of using the Time Trade-Off (TTO) method
      to isolate the effect of pure time preference from the effect of duration per se.
      Interviews were conducted with 39 members of the general population who were
      asked to rate 5 health states for durations of one month, one year and ten years.
      In aggregate, rates of time preference were very close to zero which suggests
      that the implicit assumption of the TTO method that there is no discounting may
      be a valid one. However, that more respondents had negative (rather than
      positive) rates, casts some doubt on the axions of discounted utility theory. In
      addition, implied valuations for states lasting for short periods were often
      counter-intuitive which questions the feasibility of using the TTO method to
      measure preferences for temporary health states.

PMID- 8528432
TI  - The changing distribution of a major surgical procedure across hospitals: were
      supply shifts and disequilibrium important?
AB  - This paper describes and analyzes the changing distribution across hospitals in
      the U.S. of total hip replacement surgery (THR) for the period 1980-1987. THR is
      one of the most costly single procedures contributing to health care expenses.
      Also, the use of THR exhibits a particularly high degree of geographic variation.
      Recent research pointed to shifts in demand as one plausible economic explanation
      for increasing use of THR. This paper questions whether shifts in supply may have
      been large enough to explain changes in patient mix and the relationship of
      patient mix to the number of procedures performed at a particular hospital. In
      addition, the relationship between total use of THR and the local availability of
      orthopaedic surgeons as well as the average allowable Medicare fee for
      standardized physician services is analyzed. These relationships might yield
      evidence to support a scenario of induced demand beyond the optimum for patients'
      welfare, or evidence of supply increase within a disequilibrium scenario. This
      study, using data for all THR patients in a large sample of hospitals, tends to
      reject the formulation of a market with independent supply and demand shifts
      where the supply shifts were the dominant forces. Hospitals with a larger number
      of THRs performed did not see a higher percentage of older, sicker, and lower
      income patients. It was more likely that demand shifts generated increases in
      capacity for surgical services. Moreover, there was little evidence for a
      persistent disequilibrium and only weak evidence for inducement. Also, we found
      little evidence that hospitals responded to financial incentives inherent in the
      Medicare payment system after 1983 to select among THR candidates in favour of
      those with below average expected cost. We did observe increased concentration
      over time of THR procedures in facilities with high volume--suggesting plausible
      demand shifts towards hospitals with a priori quality and cost advantages or who
      obtained those advantages with a high volume of patients.

PMID- 8528433
TI  - Demand for insurance by elderly persons: private purchases and employer
      provision.
AB  - Studies of the demand for health insurance by elderly persons often inadequately
      address the distinctions between those who receive insurance through a former
      employer and those who purchase insurance on their own. The failure to
      distinguish these two modes of supplementing Medicare can lead to an inability to
      identify the effects of important independent variables. Using data from the
      Survey of Income and Program Participation this paper examines the demand for
      employer provided health insurance among retired pensioners using a bivariate
      probit model with partial observability and compares these results to other
      models of insurance demand among elderly persons. The results indicate that
      unobserved factors reducing the probability of being offered employer provided
      insurance are associated with increased acceptance. A comparison of the employer
      provided results with results from other models of the demand for privately
      purchased insurance indicates that different independent variables may determine
      the probability of having these types of insurance. Previous studies of insurance
      that have not distinguished between these two types of insurance may not provide
      reliable estimates of the relationship between independent variables and the
      probability of insurance coverage.

PMID- 8528434
TI  - U.S. health services employment.

PMID- 8528435
TI  - Pseudo-Lyme disease.

PMID- 8528436
TI  - Vaccination in the immunocompromised person.

PMID- 8528437
TI  - Hydroxychloroquine therapy in rheumatic diseases.

PMID- 8528438
TI  - A comparison of infrared- and torch-soldering of Au-Pd and Co-Cr metal-ceramic
      alloys using a high-fusing solder.
AB  - PURPOSE: The purpose of this study was to compare the bond strengths and fracture
      modes of soldered joints formed by infrared and gas-oxygen torch heating of a
      high-fusing, gold-based solder in two metal-ceramic alloys. MATERIALS AND
      METHODS: Pairs of half-dumbbell-shaped specimens of either an Au-Pd or a Co-Cr
      alloy were positioned with a 0.25-mm gap and were joined using a high-fusing,
      gold-based solder by either gas-oxygen torch heating or infrared heating. The
      resulting specimens were subjected to a heat treatment that simulated ceramic
      firing. Each specimen was fractured in tension at a loading rate of 0.5 cm/min,
      and its bond strength was measured. The halves of the specimen were rejoined
      using the other heating method and were heat treated, and the specimen's bond
      strength was again measured. Fractured cross-sections were examined at a
      magnification of 40x to determine the following: the fracture mode (adhesive,
      cohesive, or mixed); the percentage of adhesive fracture; the presence or absence
      of voids, porosities, or flux inclusions; and the percentage of the cross-section
      that was discolored. RESULTS: Three-factor analyses of variance showed that
      neither the heating method, the particular specimen tested, nor the order of
      testing significantly affected the bond strength (P < .05). For each alloy,
      significantly fewer infrared-heated joints than torch-heated joints contained
      voids, porosities, or flux inclusions visible at 40x (chi 2 test, P < .05). All
      fractures were either entirely cohesive in the solder or mixed cohesive and
      adhesive. When infrared heating was used, entirely cohesive fractures occurred
      more frequently in the Au-Pd alloy specimens than in the Co-Cr alloy specimens
      (chi 2 test, P < .05). The coefficients of variation of the bond strengths for
      the infrared-heated joints were smaller than those for the torch-heated joints.
      CONCLUSIONS: Although the two heating methods produced solder joints that had
      strengths that were not significantly different, infrared-heated joints showed
      less scatter in bond strengths. It was suggested that, in the hands of most
      technicians, fewer infrared-heated joints would contain defects visible at a
      magnification of 40x. The presence of such defects may increase the probability
      of in vivo failure caused by cyclic stresses.

PMID- 8528439
TI  - Color stability of hybrid ionomers after accelerated aging.
AB  - PURPOSE: The color stability and surface roughness of three commercial hybrid
      ionomers were determined in vitro after accelerated aging. Three shades of each
      hybrid ionomer prepared in light-cured and dark-cured conditions were tested.
      MATERIALS AND METHODS: Samples were aged in an artificial aging chamber by
      subjecting them to total ultraviolet light irradiation of 150 kJ/m2 over a period
      of 77 hours. Color (CIE LAB system) was measured before and after aging on a
      reflection spectrophotometer. Surface roughness was measured with a profilometer.
      RESULTS: After accelerated aging, all samples became lighter. Photac-Fil Aplicap
      (ESPE-Premier, Norristown, PA) and Fuji II LC (GC America, Chicago, IL) also
      became less chromatic (less red and less yellow). Among the light-cured samples,
      Fuji II LC had the greatest change in color followed by Photac-Fil Aplicap and
      Vitremer (3M Dental Products, St Paul, MN). For the dark-cured samples, Fuji II
      LC had the greatest change in color followed by Vitremer and Photac-Fil Aplicap.
      There were no differences in delta E* between the two lightest shades, but the
      darker shades of each product showed the greatest changes in color. All samples
      became significantly rougher after aging. CONCLUSIONS: Hybrid ionomers changed
      color significantly and perceptibly after in vitro accelerated aging. Surfaces
      became significantly rougher and showed evidence of cracking and degradation.

PMID- 8528440
TI  - Predoctoral implant dentistry programs in US dental schools.
AB  - Surveys of US dental schools over the last 20 years have reported a continual
      increase in the number and types of predoctoral and postdoctoral implant
      dentistry programs being taught. The purpose of the following article is to
      report on the results of a survey intended to update the status of predoctorl
      programs with respect to their curricular placement, departmental jurisdictions,
      and course contents. In June 1993, 54 US dental schools received the implant
      dentistry curriculum survey, and 50 of the schools (93%) returned responses.
      Results indicate that the trend toward implementation of more predoctoral implant
      dentistry programs has been sustained, with 86% of schools reporting the
      existence of implant curricula. This compares with 33% and 73% of US schools
      having such programs in 1974 and 1989, respectively. The major reasons that
      schools gave for not having implant dentistry courses for predoctoral students
      are a lack of curriculum time and scarce financial resources. The dental
      disciplines most frequently guiding such programs are oral surgery and
      periodontics. Schools offer varying degrees of lectures, laboratories, and
      clinical experiences in predoctoral implant dentistry, with the number of
      curriculum hours peaking in years three and four. General curricular topics most
      commonly include a historical overview of implant dentistry, diagnosis and
      treatment planning, classifications and types of dental implants, and surgical
      and prosthodontic procedures. Seventeen percent of schools require some form of
      undergraduate clinical implant dentistry exposure for all of their students.

PMID- 8528441
TI  - The prosthodontic management of endodontically treated teeth: a literature
      review. Part III. Tooth preparation considerations.
AB  - The final part of this literature review series presents guidelines for the
      optimal preparation of teeth to receive posts and cores.

PMID- 8528442
TI  - Custom tinting denture bases by visible light cure lamination.
AB  - A urethane dimethacrylate and tinting powder lamination, chemically bonded to a
      methyl methacrylate denture base, produces a natural-appearing distribution of
      the tints. The characterization is protected by a hard, clear layer of urethane.
      Procedures are described that achieve this lamination either in the laboratory,
      before processing the dentures, or after the dentures have been fabricated.

PMID- 8528443
TI  - Fabrication and use of an intracavitary radiotherapeutic applicator for the
      posterior sinus wall: a case report.
AB  - The essential features of and the prosthodontic procedures necessary for
      fabricating a radiation applicator from dental acrylic resin for use in a
      clinical case of recurrent squamous cell carcinoma treated by intracavitary
      radiotherapy are described. A method for reducing radiation dose to the optic
      chiasm using Cerrobend alloy is presented.

PMID- 8528444
TI  - Institute of Medicine Report discourages increasing specialty residencies.

PMID- 8528445
TI  - Modalities of treatment for the combination syndrome.
AB  - A series of destructive changes occurring in the jaws of patients wearing a
      complete maxillary denture opposed by a mandibular distal extension removable
      partial denture have been described as the combination syndrome. However, the
      syndrome does not occur in all patients. Those patients who have not developed
      signs of the combination syndrome and whose mandibular anterior teeth are well
      preserved and not overerupted may be treated conservatively with a mandibular
      removable partial denture. A properly designed removable partial denture that
      distributes occlusal stresses over hard and soft tissues minimizes the risk of
      developing the combination syndrome. Nevertheless, the overdenture seems to
      provide a more predictable prognosis, especially for patients who already have
      the combination syndrome or whose mandibular anterior teeth are structurally or
      periodontally compromised or overerupted. The treatment modality is determined by
      the apparent potential of the patient to develop the combination syndrome and by
      the condition of the remaining mandibular anterior teeth.

PMID- 8528446
TI  - Modifications in the design and fabrication of mandibular osseointegrated fixed
      prostheses frameworks.
AB  - This article presents the advantages of design modifications and fabrication
      techniques for mandibular osseointegrated fixed prostheses. These design features
      provide definite mechanical advantages and access for oral hygiene maintenance. A
      review of implant surface properties is presented that affect bacterial plaque
      and food debris adherence. The suggested design involves a lingual contour of the
      cast alloy suprastructure to yield an environment for reduced plaque and debris
      accumulation. The right angle cross-section ensures strength and increased stress
      distribution in structurally compromised areas when compared with conventional
      implant framework designs.

PMID- 8528447
TI  - Anatomic site evaluation of edentulous maxillae for dental implant placement.
AB  - PURPOSE: This study evaluated 17 edentulous cadavers for bone quantity and
      quality of the alveolar process of the maxilla for the purpose of dental implant
      placement. MATERIALS AND METHODS: The maxillary arch was divided into four
      anatomically defined regions for measurements of bone quantity. Bone quality was
      assessed histologically and described by trabecular bone patterns and tissue
      composition. RESULTS: Average bone height with a minimum thickness of 4 mm was as
      follows: region 1, 12.1 +/- 4.9 mm; region 2, 14.1 +/- 7.2 mm; region 3, 6.1 +/-
      2.8 mm; and region 4, 8.5 +/- 2.2 mm. Histological evaluation showed increased
      trabeculation and thicker cortex in the maxillary anterior area, regions 1 and 2.
      Region 3, the floor of the maxillary sinus area, had the least amount of bone;
      however, the quality of bone was superior to that of region 4, the maxillary
      tuberosity area. Trabecular distance or marrow spaces ranged from 40 microns to 2
      mm with larger spaces associated with the posterior maxilla. CONCLUSIONS:
      Maxillary tuberosity is the least desirable site for the placement of implants in
      the maxilla. The area corresponding to the first and second molars had the least
      bone thickness. All measures of bone preservation need to be considered,
      especially in this area.

PMID- 8528448
TI  - A three-dimensional finite element stress analysis of angled abutments for an
      implant placed in the anterior maxilla.
AB  - PURPOSE: A three-dimensional mathematical model of the maxilla was developed that
      was used to analyze the stresses and strains produced by an abutment system
      capable of three abutment angulations. MATERIALS AND METHODS: Computed tomography
      was used to derive the geometry and density values used for the maxillary model.
      A 3.8 x 10-mm cylindrical implant was embedded in the right central incisor
      position at a 35 degrees angle to the horizontal plane and parallel to the
      angulation of the bone site. All geometric and elastic properties for the fixture
      and the surrounding bone were included in the model. A simulated occlusal load of
      178 N was applied along the long axis of 0 degrees, 15 degrees, and 20 degrees
      abutments. The mathematical models were solved by the Cray Y/MP Ohio
      Supercomputer (Cray, Eagan, MN) using the ABAQUS software program (Hibbitt,
      Karlsson, and Sorenson, Providence, RI). RESULTS: Numerical and graphic results
      were generated for the maximum (tensile) and minimum (compressive) stresses and
      strains. Principal stresses occurred predominantly in the cortical bone layers,
      whereas strains occurred mostly in the cancellous bone. CONCLUSIONS: In general,
      there was an increase in the magnitude of stress and strain as the abutment
      angulation increased. Reported stresses and strains for all three angles were
      within or slightly above the physiological zone derived from animal studies. A
      need to investigate the response of human bone to stress and strain was
      indicated.

PMID- 8528449
TI  - Investigation of thiourea activated polyglutaraldehyde with bound Ag(I) or Pt(II)
      as an alternative to avidin for immobilizing biotin conjugates.
AB  - Pre-polymerized glutaraldehyde covalently linked to thiourea has been synthesized
      as a soluble polymer for immobilizing Ag(I) and Pt(II) and it has also been used
      for activating a polyacrylamide gel filtration media. The modified gel filtration
      media (Bio-Gel P-200) has a high capacity for Ag(I) (20 mumol/ml) and Pt(II) (8
      mumol/ml) and has been shown to be stable and useful even in the presence of
      relatively high chloride (up to 1 M NaCl) and phosphate concentrations (0.25 M).
      The soluble polymer can have a Ag(I) capacity of between 2-11 mmol/g. Bio-Gel P
      200 modified using glutaraldehyde/thiourea and in the Ag(I) and Pt(II) form
      selectively binds biotinylated BSA (b-BSA) over BSA. Using the Ag(I) form of the
      gel at pH 4.8 (0.05 M phosphate) only b-BSA binds and 30% can be eluted using
      0.15 M NaCl, while no BSA binds to the column under these conditions. For the
      Pt(II) form of Bio-Gel P-200 at pH 4.8, none of the applied BSA binds to the
      modified resin while 40% of b-BSA does bind.

PMID- 8528450
TI  - Transplantation of cartilagenous tissue generated in vitro into articular joint
      defects.
AB  - The purpose of this pilot study was to determine whether isolated rabbit
      chondrocytes will form cartilagenous tissue in culture and whether this tissue
      can be used as a cartilage transplant in order to resurface damaged joints.
      Chondrocytes were isolated from rabbit articular cartilage, plated as a monolayer
      on Millicell-CMR filters and maintained in cell culture. The cells formed
      cartilagenous tissue that could be removed from the filter support by two weeks
      in culture. The chondrocytes synthesize type II collagen indicating that they
      maintained their phenotype under these conditions. For the transplant studies,
      two types of articular surface defects, either full thickness into subchondral
      bone or intra-chondral, were created in rabbits. The cartilagenous tissue was
      placed in the defect either without fixation or with the topical application of
      an adhesive agent (Cell-Tak or Nexaband Avian). The joints were examined within
      two weeks following the surgery. No transplants remained in the defects in those
      animals in which tissue fixation had been attempted with Cell-Tak. Those grafts
      fixed into the cartilage defect with Nexaband Avian remained in place but
      consisted of a condensed layer of acellular tissue. However, cartilagenous tissue
      was present and intact in five of the six animals in which the transplant had
      been placed, in the absence of adhesive, into a full thickness defect. In
      conclusion, cartilagenous tissue generated in vitro can survive transplantation
      but an appropriate method to fix grafts into intra-chondral defects is required.

PMID- 8528451
TI  - Heat-stabilized albumin microspheres as a sustained drug delivery system for the
      antimetabolite, 5-fluorouracil.
AB  - The aim of this investigation was to study the release behaviour of heat
      stabilized albumin microspheres with entrapped 5-Fluorouracil (5-FU) in vitro,
      and determine the organ distribution in vivo, for potential application in the
      treatment of ovarian cancer. Additionally, blood chemistry and haematological
      profiles were composed after intraperitoneal administration of 5-FU-loaded
      albumin microspheres into adult female Wistar rats. Microspheres with entrapped 5
      FU was also added to 10(4) HeLa cells, cultured in Eagles Minimum Essential
      Medium, and the effects of drug leakage studied. It was found that cell division
      of the cells was halted before one cell cycle, as demonstrated by the absence of
      micronuclei and double nuclei. Blood chemistry and haematology indicated mild
      systemic toxic effects of the drug e.g. bone marrow suppression and liver
      involvement, reaching a maximum by Day 12 after intraperitoneal administration of
      5-FU-microspheres. A return to normal however was observed within 4 weeks. The
      data suggest that 5-FU-loaded albumin microspheres may be beneficial in reducing
      the severe side-effects of this antimetabolite, whilst still maintaining
      therapeutic levels to cause tumour cell death.

PMID- 8528452
TI  - Poly(ethylene glycol)-serum albumin hydrogel as matrix for enzyme immobilization:
      biomedical applications.
AB  - Poly(ethylene glycol)-albumin hydrogels were implanted in mice in subcutaneous
      position to study their biocompatibility. After one month of implantation, the
      fibrous capsule formed around the implant was thin and the inflammatory tissue
      was limited. Acid phosphatase (AP) was selected to evaluate the hydrogel as
      matrix for enzyme immobilization. AP-hydrogels were prepared using activated PEG
      (PEGa) of different molecular weights (M.W. 4,600 to 20,000) to evaluate the
      effect of the matrix composition on the activity of AP. The apparent Km of the
      immobilized AP was 16 to 20 times higher than the Km of the soluble enzyme. The
      apparent Km value decreases with the increase of the chain length of the PEGa
      used. This can be correlated to an increase in the hydrogel porosity. The
      operational stability of the AP was markedly improved after immobilization by 110
      to 160 times according to the PEGa molecular weight involved. Also, asparaginase
      (ASNase) was immobilized in PEGa (M.W. 10,000)-albumin-hydrogel as a model for in
      vivo bioreactor. ASNase hydrogels were implanted in the peritoneal cavity of
      rats; 7 days later, 75% of the initial enzyme activity were retrieved.

PMID- 8528453
TI  - Study of microencapsulation for pituitary transplantation: capsule preparation
      and in vitro study.
AB  - We have developed microcapsules using sodium alginate (SA) and Poly-L-Lysine
      (PLL). A factorial design method of screening was chosen to study influences of
      different experimental parameters on size and stability of the capsules. We found
      that air flow affects initial size of the capsules significantly, while the
      molecular weight (MW) of PLL and incubation time have a positive impact on the
      expansion when capsules are incubated in sodium citrate (SC). When the capsules
      were continuously shaken in an attempt to mimic in vivo environmental conditions,
      those capsules made with optimal parameters (0.1% PLL, 42,000 MW, incubated for 6
      minutes; 1.5% SA, incubated for 4 minutes; SC bath 4 minutes; 25# needle; air
      flow 14L/min) were still intact after 30 days and not totally ruptured until 90
      days, while those developed with less strict parameters were ruptured within 2
      hours in 50%. We also encapsulated human pituitary adenoma cells using PLL of
      80,000 MW and cultured them for 9 days. Adenoma cells, both encapsulated or non
      encapsulated, secreted the same amount of hormones. Our preliminary study
      suggests that selecting optimal combinations of experimental parameters is
      essential in developing durable microcapsules, which may be potentially used for
      pituitary transplantation in vivo.

PMID- 8528454
TI  - Drug release from new bioartificial hydrogel.
AB  - The use of high water content (> 96%) hydrogels obtained from copolymerisation of
      bovine serum albumin and poly(ethylene glycol) as a controlled release system has
      been investigated. Such hydrogels allowed release of soluble and hydrophobic
      substances, even proteins. Release is shown to occur by a diffusion controlled
      mechanism, leading to half-life times of release ranging between 0.8 hour for
      theophylline and 4.2 hours for lysozyme, when a 2.4 mm thick disc of BSA-PEG (MW
      of 10000) was used. The effect of the porosity of the hydrogel on the diffusive
      properties of theophylline and hydrocortisone has been evaluated by varying the
      molecular weight of the poly(ethylene glycol). It was shown that poly(ethylene
      glycol) of high molecular weight leads to more porous hydrogels in which the
      diffusion is faster.

PMID- 8528455
TI  - Viable porcine hepatocytes from slaughterhouse organs.
AB  - A modified enzymatic isolation technique for the successful harvesting of porcine
      liver cells from slaughterhouse organs is introduced. Digestion of the left
      medial liver lobe (n = 74) resulted in 1.0 +/- 0.3 x 10E7 viable hepatocytes per
      gram tissue and an overall yield of 1.92 +/- 0.5 x 10E9 cells per isolation
      (viability: 93 +/- 2%).

PMID- 8528456
TI  - Immunohistochemical visualization of brain-derived neurotrophic factor in the rat
      brain.
AB  - A purified polyclonal antibody preparation was made against recombinant brain
      derived neurotrophic factor (BDNF) in guinea pig and characterized for use in
      immunoassays and immunohistochemistry. The anti-BDNF antibodies specifically
      recognized BDNF in Western blots and immunoprecipitation. There was no cross
      reactivity with the other known mammalian members of the neurotrophin family,
      nerve growth factor, neurotrophin-3 and neurotrophin-4/5. In immunohistochemical
      analysis, the anti-BDNF recognized exogenous BDNF injected into the brain of
      rats, whereas no signal was obtained with the other neurotrophins. Preabsorption
      with native BDNF abolished the immunoreactivity in brain sections. These studies
      identify the anti-BDNF as a tool for immunocytochemistry and the development of
      an immunoassay. Immunohistochemical analysis revealed widespread neuronal
      localization of BDNF in many brain areas. BDNF was localized in all
      subpopulations of hippocampal neurons. The distribution in the hippocampus
      suggests localization in the cytoplasm of cell bodies and dendrites.

PMID- 8528457
TI  - Cerebral energy metabolism and immediate early gene induction following severe
      incomplete ischaemia in transgenic mice overexpressing the human ornithine
      decarboxylase gene: evidence that putrescine is not neurotoxic in vivo.
AB  - Cerebral ischaemia causes activation of ornithine decarboxylase followed by
      accumulation of putrescine, and these biochemical phenomena have been thought to
      contribute to the development of neuronal damage. We have used a transgenic mouse
      line overexpressing the human ornithine decarboxylase gene in their neurons with
      constitutively high putrescine to study the possible role of putrescine in
      development of neuronal damage in forebrain ischaemia. An incomplete forebrain
      ischaemia model was developed in which common carotid arteries were bilaterally
      occluded and reduction of blood pressure caused by orthostatic reaction was used
      as a way of decreasing cerebral circulation. Cerebral high-energy metabolites,
      intracellular pH and lactate were monitored by means of 31P and 1H nuclear
      magnetic resonance spectroscopy respectively. Incomplete ischaemia for 15 min
      resulted in severe energy failure, as indicated by an increase in the inorganic
      phosphate/phosphocreatine ratio, intracellular acidification from a pH of
      approximately 7.1 to approximately 6.5 and an increase in lactate concentration
      from < 1 to approximately 10 mmol/kg in both syngenic and transgenic mice.
      Following deocclusion, recovery of energy metabolites intracellular pH and
      lactate were identical in both animal groups. Ornithine decarboxylase activity
      rose 9- and 3-fold in syngenic and transgenic mice respectively 6 h after
      ischaemia, which was approximately 50-fold greater than the basal level in
      syngenic mice. In situ hybridization experiments revealed induction of
      transcription factors c-Fos and zif-268 in the hippocampus, throughout the
      cerebral cortex and striatum 1-3 h after ischaemia. Messenger RNA of heat shock
      protein 70 was induced in dentate gyrus and CA3 and CA4 subfields of the
      hippocampus 1 h after ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528458
TI  - Early changes in prodynorphin mRNA and ir-dynorphin A levels after kindled
      seizures in the rat.
AB  - Prodynorphin mRNA and immunoreactive dynorphin A (ir-dynorphin A) levels were
      measured in different brain areas at various time points after amygdala kindled
      seizures. In the hippocampus, striatum and hypothalamus, prodynorphin mRNA levels
      were not significantly changed in kindled rats (killed 1 week after the last
      stimulus-evoked seizure), but they were significantly increased 1 h after
      seizures. The relative increase was the highest in the hippocampus (approximately
      3-fold). In the brainstem, midbrain and cerebral cortex no changes in
      prodynorphin mRNA were detected in kindled rats, 1 h or 1 week after a kindled
      seizure. ir-Dynorphin A levels were significantly reduced in the hippocampus and
      in the striatum of kindled rats, as well as 5 and 60 min after kindled seizures,
      but they were increased back to control levels after 120 min. In the
      hypothalamus, ir-dynorphin A levels were significantly increased 120 min after a
      kindled seizure. ir-Dynorphin A levels were also significantly reduced in the
      brainstem and in the frontal, parietal and temporal cortex 120 min, but not 5 or
      60 min, after a kindled seizure. Taken together, these data support the
      hypothesis that the dynorphinergic system is activated after amygdala kindled
      seizures, with different kinetics in different brain areas.

PMID- 8528459
TI  - Anti-nociception induced by systemic or PAG-microinjected lysine-acetylsalicylate
      in rats. Effects on tail-flick related activity of medullary off- and on-cells.
AB  - Previous experiments using metamizol have shown that this non-steroidal anti
      inflammatory drug (NSAID) produces a central anti-nociceptive effect probably
      through neural substrates that also support the analgesic effects of opiates,
      such as the periaqueductal grey matter (PAG) and the off- and on-cells of the
      rostral ventromedial medulla (RVM). Off- and on-cells have been postulated to
      respectively inhibit and facilitate nociceptive transmission, since the heat
      elicited tail flick reflex (TF) occurs only after off-cells have decreased
      (pause), and on-cells, have increased (burst) their activity. The aim of the
      present study was to examine whether the effect of metamizol upon TF and off- and
      on-cells responses could be generalized to other NSAIDs such as, in this case,
      lysine-acetylsalicylate (LASA). Fifty-nine off- and on-cells of the RVM were
      recorded in lightly anaesthetized rats. Systemic administration (200 and 300
      mg/kg) or PAG microinjection (30, 50 and 100 micrograms) of LASA caused
      retardation of the heat-elicited off-cell pause, on-cell burst and the
      corresponding TF. Neuronal responses and TF retained their mutual time
      relationship but shifted simultaneously toward longer latencies. This anti
      nociceptive effect of LASA was dose-dependent, present 5 min after administration
      and reached a maximum in 30 min for both administration methods. These data
      confirm that analgesics typically defined as peripherally-acting, such as
      metamizol and LASA in this study, may also have an anti-nociceptive effect by
      acting directly upon PAG, and suggest that this central effect involves the RVM
      off- and on-cells.

PMID- 8528460
TI  - Visual learning for an auditory secondary reinforcer by macaques is intact after
      uncinate fascicle section: indirect evidence for the involvement of the corpus
      striatum.
AB  - Three cynomolgus monkeys (Macaca fascicularis) were trained preoperatively in
      visual discrimination learning for an auditory secondary reinforcer. Each new
      discrimination problem was solved on the basis of the secondary reinforcer, and
      primary reinforcement (food reward) was given only after a new problem had been
      solved. The animals learned 50 new problems in each daily session and it was
      therefore possible to assess accurately their average rate of learning new
      discrimination problems in this procedure. After the learning rate had stabilized
      preoperatively the animals were operated upon to transect the uncinate fascicle,
      the cortico-cortical pathway from visual association cortex in the temporal lobe
      to prefrontal cortex. The animals' learning rate was unchanged after uncinate
      fascicle section. A previous experiment has shown that visual learning for an
      auditory secondary reinforcer is unaffected by disconnection of visual
      association cortex from the amygdala and the fornix. Taken together, this
      negative evidence points strongly to the conclusion that visual learning for an
      auditory secondary reinforcer depends upon interaction of temporal lobe visual
      association cortex with the corpus striatum, since other possibilities have been
      excluded.

PMID- 8528461
TI  - Glial cells in the mouse hippocampus express AMPA receptors with an intermediate
      Ca2+ permeability.
AB  - Recently, we could demonstrate the 'complex' glial cells in mouse hippocampal
      slices express glutamate receptor changes of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)/kainate subtypes. In the present study, we further
      characterized this glial receptor. Since voltage-clamp control is imperfect and
      diffusion barriers hinders the quantitative analysis of the receptor currents in
      situ, the patch-clamp technique was applied to glial cells acutely isolated from
      the mouse hippocampal CA1 stratum radiatum subregion. A concentration-clamp
      technique was used which enabled very fast exchange of the extracellular
      solutions. Thus, it was possible to characterize the transient receptor currents
      with high time resolution. Application of L-glutamate, AMPA and L-homocysteate
      induced rapidly activating and fast desensitizing receptor currents in the
      suspended glial cells. In contrast, kainate induced non-desensitizing currents.
      The corresponding dose-response curve revealed a half-maximum of current
      activation at 350 microM. The current/voltage relationship of the kainate-evoked
      response was linear with a reversal potential at approximately 9 mV. Analysis of
      the reversal potential in solutions containing high concentrations of CaCl2
      confirmed earlier in situ data by demonstrating significant Ca2+ permeability of
      the glial glutamate receptor channels in the hippocampus. The kainate-induced
      receptor currents were markedly increased by cyclothiazide, a substance which
      selectively potentiates glutamate receptors of the AMPA subtype. We conclude that
      glial cells of the juvenile hippocampus mainly express heteromeric high-affinity
      AMPA receptors. Most probably, the receptor channels are assembled from the low
      Ca(2+)-permeable glutamate receptor-2 subunit together with Ca(2+)-permeable AMPA
      preferring subunits.

PMID- 8528462
TI  - Extracellular activation of unitary excitatory synapses between hippocampal CA3
      and CA1 pyramidal cells.
AB  - The possibility of regular activation of unitary excitatory synapses on
      hippocampal CA1 cells by electrical stimulation of Schaffer collaterals was
      explored in the rat. The amplitude of the excitatory postsynaptic currents
      (EPSCs) and failures in response to a range of stimulation intensities around the
      threshold for the smallest detectable EPSC were analysed. After an abrupt
      appearance of EPSCs in response to increasing stimulation strength, both EPSC
      amplitude and failure rate could reach a plateau where increasing stimulation
      intensity did not cause additional responses. This was interpreted as a regular
      activation of mainly a single axon. Statistical methods showed, however, that
      only 12 out of approximately 50 experiments using threshold stimulation were
      without significant contamination from additional fibres. In this subset of
      experiments, upper limits for contamination from other fibres were estimated by
      using bootstrapping methods. More than 90% of the responses were probably due to
      faithful activation of a single axon, assuming that the density of axons
      connecting to one target cells is relatively homogeneous. This result makes the
      described method suitable for examining some aspects of the transmission between
      individual hippocampal cells.

PMID- 8528463
TI  - Transmitter release associated with long-term synaptic depression in rat
      corticostriatal slices.
AB  - Using a corticostriatal slice preparation, we have recently shown that tetanic
      stimulation of the corticostriatal pathway produces long-term depression (LTD) of
      striatal excitatory synaptic transmission. In the present study we have analysed
      the relationship between LTD and the striatal release of different endogenous
      transmitters. Samples of perfusate were collected via a small cannula placed just
      above the surface of the striatal slice close to the recording electrode, and
      were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s
      duration, 20 s interval) used to induce LTd caused a significant but transient
      increase in the release of both excitatory (aspartate and glutamate) and
      inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also
      produced a significant, but transient increase in the release of endogenous
      dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway
      is able to induce a large but transient release of excitatory amino acids and of
      dopamine, whose participation in the induction of striatal LTD has been
      demonstrated previously. Moreover, the maintenance of this form of synaptic
      plasticity does not seem to require a sustained change in transmitter release.

PMID- 8528464
TI  - Neonatal rat cerebellar granule and Purkinje neurons in culture express different
      GABAA receptors.
AB  - We have established a culture system for microexplants of rat cerebellar cortical
      tissue in which cells develop morphologically, express type-A receptors for the
      inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and form GABAergic
      synaptic connections. Criteria of cell size and shape allow reliable
      identification of granule and Purkinje neurons, criteria confirmed by studies of
      the binding of antibodies to calbindin D28K and GABA. Both granule and Purkinje
      neurons express GABAA receptors, but granule neurons fall into two classes in
      terms of their sensitivity. Granule neurons which do not show spontaneous
      synaptic currents are relatively insensitive to GABA, while granule neurons with
      synaptic currents are much more sensitive. The responses of Purkinje neurons to
      application of 1 microM GABA are relatively insensitive to Zn2+ ion (10 microM),
      and are potentiated by chlordiazepoxide (100 microM) and La3+ ions (100 microM).
      Responses of innervated granule neurons, on the other hand, are blocked more
      strongly by Zn2+ ions, are less affected by chlordiazepoxide and are equally
      potentiated by La3+ ions. Hence these cultures provide a source of identifiable,
      functionally innervated cells which express distinct types of GABAA receptors.

PMID- 8528465
TI  - Activation of class II or III metabotropic glutamate receptors protects cultured
      cortical neurons against excitotoxic degeneration.
AB  - Trans-1-aminocyclopentane-1,3-dicarboxylic acid, a mixed agonist of all
      metabotropic glutamate receptor (mGluR) subtypes, is known to produce either
      neurotoxic or neuroprotective effects. We have therefore hypothesized that
      individual mGluR subtypes differentially affect neurodegenerative processes.
      Selective agonists of subtypes which belong to mGluR class II or III, such as
      (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV) (specific for
      subtypes mGluR4, 6 or 7), were highly potent and efficacious in protecting
      cultured cortical neurons against toxicity induced by either a transient exposure
      to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. In contrast,
      agonists that preferentially activate class I mGluR subtypes (mGluR1 or 5), such
      as quisqualate or trans-azetidine-2,3-dicarboxylic acid, were inactive. DCG-IV
      was still neuroprotective when applied to cultures after the toxic pulse with
      NMDA. This delayed rescue effect was associated with a reduction in the release
      of endogenous glutamate, a process that contributes to the maturation of neuronal
      damage. We conclude that agonists of class II or III mGluRs are of potential
      interest in the experimental therapy of acute or chronic neurodegenerative
      disorders.

PMID- 8528466
TI  - Retraction of spinule-type neurites from carp retinal horizontal cell dendrites
      during dark adaptation involves the activation of Ca2+/calmodulin-dependent
      protein kinase II.
AB  - The formation of spinules at the terminal dendrites of retinal horizontal cells
      with the onset of light and their subsequent retraction during darkness is a
      remarkable example of synaptic plasticity where sensory experience modifies
      reversibly, and on a time scale of minutes the ultrastructure of synaptic
      connectivity. The signals and the subsequent intracellular cascades underlying
      the prominent morphological alterations are only partially understood. We show
      here that lowering the external calcium concentration did prevent dark- and AMPA
      induced retraction of spinules in a eyecup preparation. Furthermore, spinule
      retraction was prevented in vivo by the injection of calmidazolium, an inhibitor
      of calmodulin, into the eyeball, and also by the injection of KN-62, an inhibitor
      of Ca2+/calmodulin-dependent protein kinase (CaMkII). We conclude that local Ca2+
      influx through AMPA-gated channels followed by activation of CaMkII is an
      important step for spinule retraction during dark adaptation. The phosphorylation
      patterns of phosphoproteins derived from purified horizontal cells was affected
      by the inhibitors of calmodulin and CaMkII respectively. Some of the affected
      phosphoproteins appeared to be cytoskeleton-associated proteins, including GAP
      43. Based on these observations, a putative scenario for the retraction of
      spinules is proposed.

PMID- 8528468
TI  - Miniature endplate current kinetics at the mouse neuromuscular junction: effects
      of temperature and medium viscosity.
AB  - The time course of miniature endplate currents (MEPCs), derived by extracellular
      focal recording, was studied in the mouse neuromuscular junction at different
      temperatures and medium viscosities, and in eserine-treated endplates. At low
      temperatures (6-10 degrees C), almost the whole MEPC decay is exponential and the
      rising phase is not significantly modified by the channel closing process. At
      physiological temperatures (38-40 degrees C), the early part of the decay is much
      slower than the later part and the rising phase is made shorter and smaller by
      channel closing, showing that the channel opening and channel closing processes
      overlap remarkably. Even at physiological temperatures, however, the late part of
      the MEPC decay shows an exponential time course. At high temperatures the channel
      opening process has low temperature sensitivity and slows down when bath solution
      viscosity is increased, suggesting that at high temperatures channel opening
      kinetics may mainly be controlled by the time course of acetylcholine diffusion.
      The lower limit of conformational change rate leading to channel opening was
      estimated at 10 degrees C (4400 s-1). Experimentally recorded MEPCs were
      mathematically simulated to obtain a quantitative description of the processes
      controlling MEPC generation. Mathematical simulation further suggests that (i)
      acetylcholine diffusion kinetics may affect the onset rate of MEPCs without,
      however, being rate-limiting; and (ii) partial, transient acetylcholinesterase
      inhibition operated by acetylcholine may explain the low temperature sensitivity
      exhibited by the onset rate of MEPCs at high temperatures.

PMID- 8528467
TI  - Implication of a nitric oxide synthase mechanism in the action of substance P: L
      NAME blocks thermal hyperalgesia induced by endogenous and exogenous substance P
      in the rat.
AB  - The effects of i.p. administration of the nitric oxide synthase inhibitor NG
      nitro-L-arginine methylester (L-NAME) and its inactive isomer, D-NAME, were
      tested in two nociceptive paradigms in the rat. In the first paradigm, rats were
      lightly anaesthetized with a mixture of chloral hydrate (120 mg/kg, i.p.) and
      sodium pentobarbital (20 mg/kg, i.p.). Tail flick reaction times were monitored
      and thermal hyperalgesia was induced by immersion of the tail in hot water at 55
      degrees C for 1.5 min. In the groups of rats pretreated with saline (n = 5), 100
      mg/kg D-NAME (n = 6), 10 (n = 5) or 25 (n = 6) mg/kg L-NAME, this thermal injury
      induced a transient reduction in the reaction time that was 54-59% of the
      baseline value. However, in the groups of rats pretreated with 50 (n = 6) or 100
      (n = 7) mg/kg L-NAME the reaction times were 73.9 +/- 2.7% (P < 0.05) and 102.3
      +/- 0.9% (P < 0.001) of the baseline values respectively, indicating a block of
      the hyperalgesic responses seen in the other groups. As this hyperalgesia has
      been reported to be blocked by NK-1 receptor antagonists, it is suggested that it
      is due to the action of endogenous substance P. In the second paradigm, tail
      flick responses were monitored in the awake rat and thermal hyperalgesia was
      induced by intrathecal administration of substance P (6.5 nmol) via a chronically
      implanted catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528469
TI  - Somatosensory activations of the parietal operculum of man. A PET study.
AB  - We tested the hypothesis that somatosensory discrimination of roughness
      (microgeometry) but not of shape (macrogeometry) would activate the parietal
      operculum (PO) in man. It was also investigated whether a simple square pulse
      indentation of the skin on the index finger would activate the PO. Regional
      cerebral blood flow was measured with [15O]butanol and positron emission
      tomography in a total of 20 normal volunteers. Ten subjects used their right hand
      to discriminate objects that differed in roughness and similar smooth objects
      that differed in length. Ten other subjects pressed a button when they felt a
      square pulse indentation of the skin on their right index finger in a
      somatosensory reaction time task. Discrimination of roughness activated one field
      in the PO contralaterally and two fields ipsilaterally to the stimulated hand.
      The discrimination of length activated one field in the PO located ipsilaterally
      to the stimulated hand. The somatosensory reaction time task also activated one
      contralateral and two ipsilateral fields in the PO, and these fields partially
      overlapped the activated fields in the roughness discrimination task. Based on
      the extension of these fields and their overlaps we conclude that there exist at
      least one part of the contralateral PO and at least two parts of the ipsilateral
      PO that can be activated by somatosensory stimulation of the right hand. We argue
      further that the contralateral activated part contains a region than can be
      activated by roughness.

PMID- 8528470
TI  - Differential formation of topographic maps on the cerebral cortex and superior
      colliculus of the mouse by temporally correlated tactile- tactile and tactile
      visual inputs.
AB  - Coincident electrical activity of nerve fibres seems to play a fundamental role
      in the development of ordered connections in the CNS. To test this hypothesis on
      the formation of topographic maps we connected two cutaneous regions of the body
      of newborn mice by implanting an artificial bridge of pig hair. Through this
      procedure we produced the mechanical fusion of the ear with either the shoulder
      or the nose. In these conditions the ear not only was connected with shoulder or
      nose, but was also in relation with the nasal or the inferior portion of visual
      space. Therefore the probability of temporally correlated tactile-tactile inputs
      (ear-shoulder or ear-nose) as well as tactile-visual inputs (ear-inferior or ear
      nasal visual space) increased. By recording from the primary somatosensory cortex
      and superior colliculus, we found that the formation of topographic maps was
      based on different principles. The somatosensory cortex developed in terms of
      tactile-tactile correlated inputs, showing somatosensory neurons with receptive
      fields extending through the fused parts of the body. Conversely, the superior
      colliculus processed tactile-visual correlated inputs; we found somatosensory
      visual bimodal neurons with visual receptive fields extending into the portion of
      visual space where the artificial bridge was directed. These results suggest that
      the fusion of two body parts is represented in terms of cutaneous coordinates in
      the cortex and external world (visual) coordinates in the superior colliculus.
      Therefore the differential tactile-tactile and tactile-visual coincident activity
      seems to be correlated to the different meaning of information processing of
      these two brain regions.

PMID- 8528471
TI  - In vivo modulation of sigma receptor sites by calcitonin gene-related peptide in
      the mouse and rat hippocampal formation: radioligand binding and
      electrophysiological studies.
AB  - Possible interactions between sigma (sigma) receptor sites and calcitonin gene
      related peptides (CGRP) were investigated using receptor subtype-related
      analogues and fragment in in vivo [3H](+)SKF 10 047/sigma binding in the
      hippocampus, and electrophysiological recording of the N-methyl-D-aspartate
      (NMDA)-induced activation of CA3 pyramidal neurons, two well-established sigma
      assays. In both paradigms, CGRP and the agonist [Cys(ACM)2,7]hCGRPalpha modulated
      sigma systems. In vivo binding experiments demonstrated that CGRP and
      [Cys(ACM)2,7]hCGRPalpha inhibited 25-40% of specific [3H](+)SKF 10 047 labelling
      in the mouse hippocampal formation while the purported antagonist hCGRP8-37 was
      inactive. The specificity of this modulation was demonstrated further by the lack
      of effect of other vasoactive peptides, including the atrial natriuretic peptide,
      substance P, and its N-terminal fragment, substance P1-7. In the CA3 subfield of
      the rat dorsal hippocampus, hCGRP alpha decreased (up to 61%) the NMDA-induced
      activation of the pyramidal neurons. Conversely, the linear analogue
      [Cys(ACM)2,7]hCGRP alpha enhanced (by 85%) the NMDA-induced activation of CA3
      pyramidal neurons, while the antagonistic fragment hCGRP8-37 had no effect.
      Haloperidol, a high-affinity sigma receptor ligand, inhibited by 90% the in vivo
      [3H](+)SKF 10 047 labelling, and prevented the modulation of the NMDA-induced
      activation by hCGRP alpha and [Cys(ACM)2,7]hCGRP alpha. It thus appears that CGRP
      can modulate sigma-related systems in the hippocampal formation.

PMID- 8528472
TI  - Guidance of thalamocortical axons by growth-promoting molecules in developing rat
      cerebral cortex.
AB  - Substrate-bound guidance cues play an important role during the development of
      thalamocortical projections. We used time-lapse video microscopy to study the
      growth behaviour of thalamic axons on different substrates. On embryonic cortical
      membranes and on a pure laminin substrate, thalamic fibres advanced relatively
      slowly (approximately 15 microns/h) and on average their growth cones retracted
      transiently every approximately 5 h. In contrast, on membranes prepared from
      early postnatal cortex, thalamic fibres grew twice as fast and spontaneous growth
      cone collapse occurred approximately 8 times less often. Experiments in which we
      used the sugar-binding lectin peanut agglutinin or heat inactivation to change
      the membrane properties indicated that these differences are due to growth
      supporting molecules on postnatal cortical membranes. When offered a choice
      between embryonic and postnatal cortical membranes, thalamic axons preferred the
      postnatal membrane substrate. Time-lapse imaging revealed that borders between
      these two substrates effectively guided thalamic fibres, and in most cases axons
      changed their direction without collapse of the growth cone. Our results suggest
      that thalamic axons can be guided by the spatial distribution of growth-promoting
      molecules in the developing cortex.

PMID- 8528473
TI  - Optical imaging of the layout of functional domains in area 17 and across the
      area 17/18 border in cat visual cortex.
AB  - Optical imaging based on intrinsic signals was used to investigate the functional
      architecture of cat area 17 and the border between areas 17 and 18. The visual
      stimuli were gratings of different spatial frequencies moving at different
      angles, in different directions and with different speeds. In area 17 the iso
      orientation domains were usually organized in patches rather than as elongated
      bands. Patches with different orientation preferences were arranged radially
      forming 'pinwheels' around 'orientation centres'. The pinwheel density was
      approximately 1.7-fold higher than in area 18. To explore clustering according to
      direction of motion, stimuli having the same orientation but moving in opposite
      directions were used. These two stimuli yielded very similar activity maps giving
      no indication of robust directionality clustering. Using near infrared light we
      were able to simultaneously image ocular-dominance and iso-orientation domains. A
      quantitative assessment of the relative strengths of the two subsystems showed
      that in upper cortical layers clustering according to orientation preference was
      three-fold stronger than clustering according to ocular dominance. The functional
      organization of spatial frequency was also examined. When we compared the
      activated regions by stimuli having different spatial frequency and moving at
      different velocities we observed that neurons were clustered also in these
      respects. We also investigated the functional architecture at the area 17/18
      border and found that orientation maps at both sides of the border were not
      independent of each other. The map of area 17 smoothly blended into that of area
      18. Similarly, the preferred spatial frequency of the neurons changed gradually
      over a distance of approximately 0.8 mm at the region of the area 17/18 border.

PMID- 8528474
TI  - Properties of unitary IPSPs evoked by anatomically identified basket cells in the
      rat hippocampus.
AB  - Hippocampal pyramidal cells receive GABA-mediated synaptic input from several
      distinct interneurons. In order to define the effect of perisomatic synapses,
      intracellular recordings were made with biocytin-containing microelectrodes from
      synaptically connected inhibitory and pyramidal cell pairs in subfields CA1 and
      CA3 of the rat hippocampus. Subsequent physiological analysis were restricted to
      the category of cells, here referred to as basket cells (n = 14), which had an
      efferent synaptic target profile (n = 282 synaptic contacts) of predominantly
      somatic (48.2%) and proximal dendritic synapses (45.0%). Electron microscopic
      analysis revealed that in two instances identified postsynaptic pyramidal cells
      received a total of 10 and 12 labelled basket cell synapses respectively. At an
      average membrane potential of -57.8 +/- 4.6 mV, unitary inhibitory postsynaptic
      potentials (IPSPs; n = 24) had a mean amplitude of 450 +/- 238 microV, a 10-90%
      rise time of 4.6 +/- 3.2 ms and, measured at half-amplitude, a mean duration of
      31.6 +/- 18.2 ms. In most instances (n = 19) the IPSP decay could be fitted with
      a single exponential with a mean time constant of 32.4 +/- 18.0 ms. Unitary
      basket cell-evoked IPSPs (n = 5) was extrapolated to be at -74.9 +/- 6.0 mV.
      Averages of unitary IPSPs had a mean calculated conductance of 0.95 +/- 0.29 nS,
      ranging from 0.52 to 1.16 nS. Unitary basket cell IPSPs (n = 3) increased in
      amplitude by 26.6 +/- 19.9% following bath application of the GABAB receptor
      antagonist CGP 55845A [correction of CGP 35845A] (1-4 microM), whereas subsequent
      addition of the GABAA receptor antagonist bicuculline (10-13 microM) reduced the
      IPSP amplitude to 13.5 +/- 3.1% of the control response. Rapid presynaptic trains
      of basket cell action potentials resulted in the summation of up to four
      postsynaptic responses (n = 5). However, any increase in the rate of tonic firing
      (2- to 10-fold) led to a > 50% reduction of the postsynaptic response amplitude.
      At depolarized membrane potentials, averaged IPSPs could be followed by a
      distinct depolarizing overshoot or postinhibitory facilitation (n = 4). At firing
      threshold, pyramidal cells fired postinhibitory rebound-like action potentials,
      the latter in close temporal overlap with the depolarizing overshoot. In
      conclusion, hippocampal basket cells have been identified as one source of fast,
      GABAA receptor-evoked perisomatic inhibition. Unitary events are mediated by
      multiple synaptic release sites, thus providing an effective mechanism to avoid
      total transmission failures.

PMID- 8528475
TI  - Vestibulo-ocular response of human subjects seated in a pivoting support system
      during 3 Gz centrifuge stimulation.
AB  - The vestibulo-ocular reflex (VOR) and spatial orientation perceptions were
      recorded in 15 subjects during 3 Gz centrifuge runs. These data were obtained to
      study two issues: (1) to gain insight into reports of asymmetrical disorientation
      and disturbance during acceleration and deceleration of centrifuge runs like
      those used to train pilots on the procedures to counteract G-induced loss of
      consciousness (G-LOC); (2) to study the effects of sustained vertical linear
      acceleration on the vestibular system. The centrifuge angular velocity profile
      consisted of a 19 s angular acceleration to 3 Gz that was sustained for 5 min
      during a period of constant angular velocity, and a 19 s deceleration to 1 Gz.
      The runs were repeated three times with the subject facing the motion and three
      times with the subject's back to the motion. The VOR and spatial orientation
      perceptions from the eight subjects who completed all six runs were analyzed. The
      total VOR response during acceleration and deceleration was composed of
      interacting angular (AVOR) and linear components (LVOR). Asymmetries in pitch
      orientation perception between centrifuge acceleration and decleration were not
      matched by asymmetries in the total VOR slow phase velocity. During the constant
      velocity high-G phase of the run, sustained up-beating LVOR (Lz nystagmus) was
      present in 14 of the 15 subjects. Significant individual differences in Lz
      nystagmus were found, but the maximum Lz response in our 15 subjects was probably
      of insufficient magnitude to degrade visual scan of cockpit instruments. Mean
      magnitudes ranged from 0 to 10 deg/s at 90 s from onset of centrifuge run.

PMID- 8528476
TI  - The linear vestibulo-ocular reflex in normal subjects and patients with
      vestibular and cerebellar lesions.
AB  - We measured the horizontal linear vestibulo-ocular reflex (LVOR) in normal human
      subjects and patients with abnormal angular vestibulo-ocular reflexes (AVOR) and
      abnormal smooth pursuit. Eye movements were induced by sinusoidal linear
      acceleration along the interaural axis (0.8 Hz, 0.5 g peak acceleration) on a
      parallel swing. Horizontal movement of each eye was recorded with an infrared
      limbus tracking device. Normal subjects increased LVOR sensitivity as real or
      imagined targets moved closer. Perceived target distance was more important than
      the vergence angle since changing the vergence angle alone with prisms resulted
      in only a slight change in LVOR sensitivity. Subjects suppressed the LVOR with
      real or imagined head-fixed targets. Patients with decreased horizontal AVOR
      responses had decreased horizontal LVOR responses with imagined earth-fixed
      targets in the dark. They were able to generate normal velocity LVOR responses
      with real earth-fixed targets. Patients with increased AVOR responses and poor
      smooth pursuit due to cerebellar atrophy had low LVOR responses that were
      minimally affected by real or imagined earth-fixed or head-fixed targets. We
      conclude that the smooth pursuit system and the cerebellum are critical for
      generating the eye movements required as subjects fixate a near target during
      translational head movements.

PMID- 8528477
TI  - Clinical features of mal de debarquement: adaptation and habituation to sea
      conditions.
AB  - A survey conducted among 116 crew members of seagoing vessels confirmed that mal
      de debarquement (M-D) is a transient feeling of swinging, swaying, unsteadiness,
      and disequilibrium. None of the subjects requested medical attention, although
      there were isolated cases in which a strong sensation of swinging and
      unsteadiness caused transient postural instability and impaired the ability to
      drive. In most cases, the sensation of M-D appeared immediately on disembarking
      and generally lasted a few hours. In addition, subjects usually described bouts
      or attacks of M-D associated with changes in body posture, head position, or with
      closing of the eyes. M-D was reported by 72% of our subjects. Sixty-six percent
      of subjects reported a high incidence following their first voyages. A
      significant positive correlation was found between M-D and seasickness
      susceptibility. The nature of M-D may be explained within the framework of
      multisensorimotor adaptation and habituation to a new or abnormal motion
      environment. It is suggested that M-D represents a dynamic, multisensorimotor
      form of CNS adaptive plasticity.

PMID- 8528478
TI  - Head slippage during broad-frequency rotational chair testing.
AB  - Broad-frequency rotational chair testing is employed in clinical and research
      settings to evaluate the response of the vestibulo-ocular reflex (VOR) over a
      range of frequencies. Accurate computation of the gain and phase of the VOR is
      dependent upon the assumption that the subject's head is rigidly coupled to the
      rotating chair over the range of frequencies employed. We tested this assumption
      by examining head slippage in 20 normal subjects using a standard rotational
      chair over the frequency range 0.025 to 2 Hz. Measurements were made with the
      subjects' head optimally restrained according to our standard clinical protocol
      and with the head minimally restrained. Head slippage was expressed as gain and
      phase of the head with respect to the chair. Computation of these parameters was
      made by comparing the signal received from a biteblock-mounted rate sensor
      rigidly coupled to the skull with that of the chair's tachometer. We found highly
      significant slippage of the head with respect to the chair occurred at 0.5, 1 and
      2 Hz, even with the head optimally restrained, leading to increased gain and a
      phase lag. Gain and phase were highly variable for both conditions at 2 Hz
      indicating inadequate head fixation using our methods. Below 0.5 Hz, minimal head
      slippage occurred whether the head was restrained or simply rested against a
      contoured headrest. Consideration of these results may lead to changing some
      practices currently employed in broad-frequency rotational chair testing at
      frequencies of 0.5 Hz and above.

PMID- 8528479
TI  - Assessment of vestibular function by videonystagmoscopy.
AB  - Videonystagmoscopy has been used to subjectively observe the responses of the
      vestibular system in a population of patients with vestibular deficits. These
      results were compared with those of a control group of healthy, age-matched
      volunteers. The videonystagmoscopy device is made of one or two CCD cameras
      mounted on lightproof goggles, allowing a subjective observation of ocular
      movements on a video monitor. The eye movements, as well as the position of the
      head in space, can be recorded on videotape. The eyes are illuminated by infrared
      light emitting diodes placed on each side of the camera lens. The subjects are
      seated on a manually driven Barany chair. Subjects went through a protocol of
      passive roll head tilt on each side, followed by a slow, whole body rotation of
      180 degrees amplitude, clockwise and counterclockwise, and then a head shaking
      test (HST). The eyes were subjectively observed, and we focussed on: torsional
      eye movements during head tilt, nystagmus when the rotation had stopped, and
      nystagmus induced by HST. With this simple and noninvasive examining procedure,
      screening of vestibular function at the bedside or during E.N.T. clinical
      investigations is possible.

PMID- 8528480
TI  - Malignant pleural mesothelioma: newer aspects of carcinogenesis, molecular
      genetics, and prospects for future therapies.
AB  - Malignant pleural mesothelioma (MPM) is an asbestos-related disease which,
      although rare, is having a major social impact, and is, for the majority of
      cases, an incurable illness. There has been a surge of information regarding data
      on mesothelial transformation, mesothelioma molecular genetics and somatic gene
      therapy for this disease. This report summarizes the most recent investigations
      attempting to characterize the behaviour, on a cellular and molecular level, of
      MPM, with an emphasis on data from investigations performed at the National
      Cancer Institute with our collaborators.

PMID- 8528481
TI  - Surgical management of melanoma.
AB  - The incidence of melanoma is rising more rapidly than any other malignancy. More
      conservative margins of excision have been established and the role of elective
      node dissection awaits determination by prospective randomized trials.
      Lymphoscintigraphy has clarified lymphatic drainage from watershed areas.
      Lymphatic mapping and sentinel node biopsy may lead to acceptance of selective
      lymphadenectomy, and also allows for more sensitive staging. Further advances in
      outcome require the development of effective systemic adjuvant therapies. Until
      such time, surgery continues to play a pivotal role in all stages.

PMID- 8528482
TI  - Heat shock proteins are differentially expressed in human gastrointestinal
      cancers.
AB  - The heat shock proteins (Hsp) are stress-responsive genes present in all species;
      increases of Hsp can confer chemotherapeutic resistance to certain cancers. The
      purpose of this study was to determine Hsp expression in human gastric,
      pancreatic and colon cancers. Gastric (n = 3), pancreatic (n = 6) and colon (n =
      8) cancers were extracted for RNA and protein, and Northern and Western blots
      performed. We found that hsp70 and hsp27 mRNA levels were differentially
      expressed in the gastrointestinal cancers; mRNA expression closely correlated
      with protein levels suggesting regulation at the level of transcription. In
      addition, Hsp90 and BiP proteins were constitutively expressed in the
      gastrointestinal cancers. We conclude that the Hsp are differentially expressed
      in human gastric, pancreatic and colon cancers; these increases in Hsp occur
      constitutively and are not the result of physiological or environmental stresses.
      Increases of Hsp expression in cancer cells may enhance resistance and account
      for the altered sensitivity of certain gastrointestinal cancers to
      chemotherapeutic agents.

PMID- 8528483
TI  - Pharmacokinetic evaluation of percutaneous hepatic venous isolation for
      administration of regional chemotherapy.
AB  - Hepatic artery infusion (HAI) chemotherapy has been used to treat patients with
      unresectable liver tumours. We report a preclinical study of the pharmacokinetics
      of HAI combined with hepatic venous drug extraction (HVDE) for regional
      administration of doxorubicin. HVDE was aided by a double balloon catheter
      inserted via femoral vein cutdown into the inferior vena cava to collect all
      hepatic vein blood. Pigs received doxorubicin 0.5-9.0 mg kg-1 over 90 min via HAI
      or systemic infusion (SYSI). HVDE was performed for 240 min. SYSI pigs underwent
      hepatic venous isolation without drug filtration. Doxorubicin levels were assayed
      using high-pressure liquid chromatography (HPLC). HAI/HVDE reduced systemic
      exposure to doxorubicin with equivalent hepatic exposure at all doses.
      Pharmacokinetic enhancement ranged from 7.0 to 22.3 for peak concentration, 8.8
      23.2 for the area under the curve and 2.9-4.2 for tissue concentration. HAI/HVDE
      also prevented the mortality which was observed with SYSI administration of high
      dose (5.0 and 9.0 mg kg-1) doxorubicin. We conclude that HAI/HVDE reduces
      systemic exposure to doxorubicin as compared with SYSI of equivalent doses.
      Pharmacokinetic enhancement indices suggest that HAI/HVDE may allow equivalent
      hepatic drug exposure with reduced systemic exposure. This method may be
      applicable to other drugs and to other anatomic settings in which enhanced
      regional drug delivery is desirable.

PMID- 8528484
TI  - Various types of hemipelvectomy for soft tissue sarcomas: complications, survival
      and prognostic factors.
AB  - Fifty-three hemipelvectomies were performed for primary or recurrent soft tissue
      sarcomas with fixation to the pelvis or peripelvic tissues. Resection was carried
      out in the absence of distant metastases in 70% of the cases. The hemipelvectomy
      was posterior in 66%, anterior in 6% and internal in 28%. Post-operative
      complications included wound edge necrosis in 19% and infection in 43% of cases.
      The mortality rate was 5.7%. Margins were macroscopically clear in 76% and
      marginal in 24% of cases. Tumours were high grade in 92%; their mean diameter was
      16.5 cm. Local recurrence occurred in 19% and distant recurrence in 66% of
      patients. Overall survival was 39% at 2 years and 10% at 5 years. Pelvic soft
      tissue sarcomas have a poor prognosis. However, in the absence of other effective
      therapy, hemipelvectomy provides local control with acceptable morbidity in the
      majority of patients, with a small percentage (10%) surviving 5 years or longer.

PMID- 8528485
TI  - Sphincter-saving surgery with and without pre-operative radiation therapy as
      treatment for adenocarcinoma of the mid-rectum.
AB  - AIMS: To determine if pre-operative radiation therapy induces a local response in
      patients with complete tumour penetration into the rectal wall and allows for
      anal sphincter preservation, we compared the results from pathological specimens
      and local recurrences as measurable end-points in patients treated with pre
      operative radiation therapy plus low anterior resection vs. those only treated
      with low anterior resection. METHODS: From January 1986 to December 1992, we
      treated 62 patients with mid-rectal adenocarcinoma (5-10 cm from the anal verge
      as determined by rigid proctosigmoidoscopy with the patient in the jackknife
      position). Pre-operative evaluation included: complete blood cell count,
      chemistry profile and the determination of carcinoembryonic antigen, chest X-ray,
      barium enema or colonoscopy and CT scan of the abdomen and pelvis. Only tumours
      potentially curative by resection in patients with performance status 0-2 (ECOG)
      were included. Twenty-one patients received pre-operative radiation therapy at a
      dose of 45 Gy delivered to the pelvis; 4-8 weeks later a low anterior resection
      was performed. Forty-one patients were treated with low anterior resection alone.
      Surgical specimens were classified according to the Astler-Coller modification of
      Dukes' classification. RESULTS: There were 36 males and 26 females, with a mean
      age of 56 years. The surgical specimens of those treated only with surgery were
      classified as: A, 5; B1, 4; B2, 15; C1, 2; and C2, 15. Postirradiated specimens:
      no residual tumour, 3; A, 4; B1, 4; B2, 7; C2, 3. One surgical death occurred in
      the group who underwent surgery alone. The median follow-up was 50 months in
      patients treated with surgery alone vs. 62 months in the combined approach group.
      Local recurrences occurred in 15/40 patients treated with surgery alone and in
      2/21 of those treated with the combined approach (P = 0.043). Anal sphincter
      continence was classified as excellent by 24/40 patients treated with surgery
      only and by 18/21 patients treated with the combined approach. The 5-year
      survival period was 58% in the surgery only group and 82% in the group with
      combined treatment (P = 0.08). CONCLUSIONS: The use of pre-operative radiation
      therapy plus low anterior resection was associated with a lower rate of local
      recurrence and with a higher number of surgical specimens with no lymph node
      metastases. Thus, this combined treatment modality should be further evaluated as
      a possible treatment of mid-rectal cancers in good surgical candidates selected
      for sphincter-saving procedures.

PMID- 8528486
TI  - Ventricular fibrillation is not always due to multiple wavelet reentry.
AB  - INTRODUCTION: It is not known whether ventricular fibrillation (VF) is always
      caused by multiple wavelet reentry, or if it could also be caused by a single
      wandering reentrant wavefront. Activation mapping of the entire ventricles during
      VF is practically impossible. METHODS AND RESULTS: We studied VF in a two
      dimensional sheet of left ventricular subepicardial tissue of isolated,
      Langendorff-perfused pig hearts. Left and right endocardial cryoablation via
      probes filled with liquid nitrogen caused coagulation necrosis of the right
      ventricle, interventricular septum, and most of the left ventricular wall,
      leaving a thin subepicardial layer intact. Left ventricular epicardial activation
      patterns were constructed based on simultaneous recording of 128 unipolar
      extracellular electrograms. Regular pacing through a central electrode before and
      after freezing revealed that, following cryoablation, the activation pattern no
      longer showed evidence of involvement of the Purkinje system, and that it was
      compatible with propagation through a two-dimensional anisotropic tissue sheet.
      VF was induced by burst pacing. When the mass of surviving subepicardium was < 10
      g, no VF could be induced; when it was between 10 and 20 g, VF was nonsustained;
      when it was > 20 g, VF was sustained. Unipolar extracellular electrograms during
      VF before and after cryablation could not be distinguished from each other;
      however, epicardial activation patterns were markedly different. In the intact
      left ventricle, up to six different wavefronts were simultaneously present during
      a 100-msec time window. In the "frozen heart," during a period of about 0.5
      seconds, at most two wandering reentrant waves were simultaneously present;
      sometimes only one reentrant wave was seen in a 100-msec time window. CONCLUSION:
      The extracellular waveform during VF can be caused by different forms of reentry:
      multiple wavelet reentry (on the order of six different wavefronts), two
      independent wandering reentrant waves, and a single wandering reentrant wave.

PMID- 8528487
TI  - Computation of heart surface potentials using the surface source model.
AB  - INTRODUCTION: The bidomain model of the heart leads to the result that the volume
      density of cardiac current source moment is proportional to the gradient of the
      macroscopic transmembrane action potential distribution. If the anisotropy ratios
      of the inner and outer domains (syncytia) of the myocardium are equal, then the
      volume distribution of cardiac sources can be replaced by an appropriate double
      layer on the heart surface. The double layer source distribution (heart surface
      source model) provides a basis for calculating heart surface potentials from
      cardiac sources. METHODS AND RESULTS: The heart surface model was used to
      calculate epicardial potentials for the normal heart as well as for a case of
      ischemia and of infarction. The model was also used to determine the effect of
      insulating the heart surface. Insulating the heart surface caused an almost
      fourfold increase in peak-to-peak amplitude of simulated electrograms, with
      little change in waveshape. Simulated electrograms showed good agreement with
      recorded electrograms reported in the literature. CONCLUSION: The heart surface
      source model appears to provide a basis for relating heart surface potentials to
      the distribution of cellular action potential.

PMID- 8528488
TI  - Reperfusion arrhythmias: role of early afterdepolarizations studied by monophasic
      action potential recordings in the intact canine heart during autonomically
      denervated and stimulated states.
AB  - INTRODUCTION: The precise mechanism of reperfusion arrhythmias is not
      established. The role of early afterdepolarizations (EADs) and triggered activity
      in the genesis of reperfusion ventricular arrhythmia was investigated. METHODS
      AND RESULTS: Monophasic action potentials (MAPs) were recorded in the canine
      heart using Ag-AgCl contact electrodes from the left and right ventricular
      endocardium and the left ventricular epicardial border zone during 10 minutes of
      occlusion of the proximal left anterior descending coronary artery followed by 2
      minutes of reperfusion. Ventricular arrhythmias during ischemia and reperfusion
      were studied in three autonomically varied groups. Group 1 (n = 8) had intact
      autonomic neural innervation; group 2 (n = 8) had bilateral transection of ansae
      subclavii and vagi; and group 3 (n = 8) underwent bilateral transection of ansae
      subclavii and vagi with bilateral ansae subclavii stimulation during reperfusion.
      Ventricular fibrillation (VF) on reperfusion occurred in 2, 3, and 5 animals in
      the innervated, denervated, and sympathetically stimulated groups, respectively.
      Rapid ventricular tachycardia during ansae subclavii stimulation, antecedent to
      VF, occurred in 4 of 5 episodes in the sympathetically stimulated group. The
      frequency of premature ventricular complexes, couplets, and triplets on
      reperfusion was not significantly different among the three groups. Phase 2 or
      phase 3 EADs were noted during the acute ischemic phase in 6 of 8, 7 of 8, and 7
      of 8 animals in the three groups, respectively (and persisted during reperfusion
      in the majority). Thus, these EADs were not a de novo phenomenon during
      reperfusion. Of the 72 MAP recording sites, only one demonstrated de novo phase 2
      EADs during reperfusion. EADs disappeared during reperfusion in 6 animals (prior
      to the onset of VF in 4), and 5 dogs developed reperfusion VF without EADs being
      recorded. There was no direct correlation between the presence of EADs during
      reperfusion and the development of VF. The prevalence and onset of reperfusion VF
      was not significantly different in the presence of sympathetic stimulation.
      CONCLUSION: This study demonstrates that EADs can be recorded in the majority of
      dogs during both ischemia and reperfusion and do not appear to be a major
      mechanism responsible for reperfusion ventricular tachycardia and VF.

PMID- 8528489
TI  - Radiofrequency ablation of a supraventricular tachycardia due to interatrial
      conduction from the recipient to donor atria in an orthotopic heart transplant
      recipient.
AB  - Interatrial conduction of recipient atrial tachycardia to the donor atria of an
      orthotopic heart transplant recipient resulted in a unique cause of
      supraventricular tachycardia. An electrophysiologic study was performed, and the
      recipient atria was found to be in an atrial tachycardia, cycle length of 210
      msec, with periods of both 2:1 and 1:1 conduction to the donor atria resulting in
      a donor atrial cycle length of 420 msec and 210 msec, respectively. The site of
      interatrial conduction was mapped to the right atrial suture line, along the
      atrial free wall, and was successfully disrupted with radiofrequency energy.
      Arrhythmias of a similar mechanism may also be observed in other postsurgical
      patients.

PMID- 8528490
TI  - Determination of impulse conduction characteristics at a microscopic scale in
      patterned growth heart cell cultures using multiple site optical recording of
      transmembrane voltage.
AB  - It is well established that impulse propagation in cardiac tissue is determined
      by the interaction between active membrane properties and the passive electrical
      characteristics of the network formed by individual myocytes. In the past, the
      intricate microarchitecture of intact cardiac tissue and the limited spatial
      resolution of available recording techniques had rendered a systematic evaluation
      of the influence of the cellular microarchitecture on impulse propagation
      difficult. Recently, however, successful efforts have been undertaken to: (1)
      simplify the cellular arrangement by designing cardiac structures with defined
      two-dimensional geometries; and (2) measure impulse propagation in these
      preparations at the cellular/subcellular scale using optical techniques. This
      short review considers both of these developments, i.e., patterned growth of
      heart cells in culture and multiple site optical recording of transmembrane
      voltage (MSORTV), and summarizes first results obtained with the combination of
      both techniques.

PMID- 8528491
TI  - The clinical spectrum of neurocardiogenic syncope.
AB  - Neurocardiogenic syncope is a collective term used to describe the clinical
      syndromes of syncope that result from inappropriate, and often excessive,
      autonomic reflex activity, and manifest as abnormalities in the control of
      vascular tone and heart rate. These include carotid sinus syndrome, vasovagal
      syncope, and the syndromes of cough, deglutition, and micturition syncope.
      Orthostatic hypotension, which, in contrast, results from a failure of autonomic
      reflexes, is not considered part of this family of closely related syndromes.
      This review will focus on vasovagal and carotid sinus syndromes.

PMID- 8528492
TI  - How can we facilitate spontaneous termination of ventricular fibrillation and
      prevent sudden cardiac death? A working hypothesis.
AB  - Ventricular fibrillation (VF) is one of the most life-threatening arrhythmias
      encountered in daily clinical practice. Its occurrence cannot be completely
      prevented by currently used antiarrhythmic drugs, and, in most instances, VF is
      sustained and leads to the patient's death unless a successful DC defibrillation
      is applied. However, spontaneous reversion of VF to sinus rhythm has been
      observed in various animals and occasionally even in man. Hence, facilitation of
      self-ventricular defibrillation must be explored as an alternative therapeutic
      approach. In experimental studies using several mammalian species, we have found
      that self ventricular defibrillation requires a good intercellular coupling and
      well synchronized electrical activity in the ventricles, which, in untreated
      animals, depend on their myocardial catecholamine content. It can then be
      hypothesized that any agent that elevates the catecholamine level during VF would
      facilitate spontaneous ventricular defibrillation, and drugs inhibiting
      extraneuronal catecholamine reuptake have indeed been shown to possess this
      ability. It is suggested that their effects are mediated by an increase in the
      intracellular cAMP level, and any compounds sharing this property could well
      prove efficacious in making VF transient and in reducing sudden cardiac death.

PMID- 8528493
TI  - Hypoxic cellular deterioration and its prevention by the amino acid taurine in a
      transplantation model with renal tubular cells (LLC-PK1).

PMID- 8528494
TI  - An alternative medium supplement for the culturing and growth of human peritoneal
      mesothelial cells.

PMID- 8528495
TI  - A macrophage-smooth muscle cell co-culture model: applications in the study of
      atherogenesis.

PMID- 8528496
TI  - Donor site, age, and health affect fibroblast growth in culture.

PMID- 8528497
TI  - Arginine consumption as a monitor of mycoplasma infection of cultured cells.

PMID- 8528498
TI  - A digitized fluorescence imaging study of intracellular Ca2+, pH, and
      mitochondrial function in primary cultures of rabbit corneal epithelial cells
      exposed to sodium dodecyl sulfate.
AB  - Primary cultures of rabbit corneal epithelial cells have been developed as an in
      vitro system to predict irritancy potential and delayed cytotoxicity of
      surfactants in our laboratory. The objective of this study was to evaluate the
      effects of the surfactant sodium dodecyl sulfate (SDS), a common ingredient in
      consumer products, on intracellular Ca2+, pH, and mitochondrial function in this
      culture system. Ca2+ and pH were measured in single living corneal epithelial
      cells by ratio imaging of fura-2 and 2,'7'-bis(carboxyethyl)-5(6)
      carboxyfluorescein fluorescence, respectively. Mitochondrial function was
      examined by probing mitochondrial membrane potential with the fluorescent dye
      rhodamine 123 and by measuring the ratio of ATP to ADP with an HPLC method. Cell
      viability was determined by fluorescence imaging of propidium iodide in single
      cells and LDH leakage assay in populations of cells. SDS (40 micrograms/ml)
      increased intracellular Ca2+ from 180 +/- 28nM to 453 +/- 86 nM within 2 min, and
      induced intracellular acidification (pHi dropped 0.3 units in 15 min). Treatment
      of the cultures with SDS also resulted in dissipation of the mitochondrial
      membrane potential and decrease of intracellular ATP/ADP. SDS-induced Ca2+
      elevation and intracellular acidification preceded the loss of cell viability
      observed 20 min after exposure. However, SDS-induced cell injury does not appear
      to be triggered by extracellular Ca(2+)-influx, as absence of extracellular Ca2+
      did not attenuate SDS-induced cytotoxicity while it completely blocked ionomycin
      induced cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528499
TI  - Human epidermis reconstructed on synthetic membrane: influence of experimental
      conditions on terminal differentiation.
AB  - Cell suspensions of human keratinocytes seeded onto cell culture inserts may
      undergo terminal differentiation in the absence of fibroblasts. Among the
      parameters that control these morphogenic events, exposure to air and the
      composition of the culture medium were investigated. In the latter case, three
      media were considered DMEM:Ham's F12, MCDB 153, and keratinocyte SFM medium at
      equivalent calcium (1.5 mM) and fetal calf serum (5%) concentrations.
      Immunochemical methods and transmission electron microscopy show that cells
      cultured in DMEM:Ham's F12 medium, and then raised at the air-liquid interface,
      form a basal layer plus suprabasal cell layers corresponding to the stratum
      spinosum, stratum granulosum, and stratum corneum. The suprabasal keratinocyte
      layers show morphologies that resemble intact skin in which cells are connected
      by desmosomes and contain intermediate filaments and keratohyalin-filaggrin
      granules. When the cultures are kept submerged, the keratinocytes show occasional
      keratohyalin granules and are connected by fewer desmosomes. Additionally, no
      proper stratum corneum is formed. In keratinocyte SFM medium and MCDB 153,
      cultures raised at the air-liquid interface are not able to form an epithelium of
      normal architecture and do not express terminal differentiation markers.
      Differentiation is initiated, however, since desmosomes and bundles of keratin
      filaments appear; on the other hand, filaggrin is not expressed even after 28 d
      in culture. Membrane-bound transglutaminase is expressed throughout the entire
      suprabasal compartment in MCDB153 and DMEM:Ham's F12 media but never appears in
      keratinocyte SFM medium. These studies show the relative independence of
      epidermal differentiation program to the composition (including the calcium
      concentration) of the media contacting the dermis and filling the extracellular
      space.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528501
TI  - Formation of spicules by sclerocytes from the freshwater sponge Ephydatia
      muelleri in short-term cultures in vitro.
AB  - Cells from the freshwater sponge Ephydatia muelleri were isolated by dissociating
      hatching gemmules. During the first 24 h the cells reaggregated, but the
      aggregates progressively disintegrated again to single cells, among which the
      spicule-forming sclerocytes were recognized. Such cultures were used to study
      spicule (megascleres) formation in vitro. The isolated sclerocytes formed the
      organic central axial filament onto which they deposited inorganic silicon. The
      size of the spicules (200 to 350 microns in length) as well as the rate of
      spicule formation (1 to 10 microns/h) under in vitro conditions were similar to
      the values measured in vivo. Immediately after completion of spicule formation,
      or even before, the sclerocyte could start formation of a new spicule; 5% of the
      cells were in the process of forming two spicules simultaneously. Cultivation of
      sclerocytes in the absence of silicon resulted in the formation of the axial
      filament only. We succeeded in maintaining the sclerocytes in a proliferating and
      spicule-forming state for up to 3 mo. These results demonstrate that the
      establishment of short-term cell cultures from E. muelleri is possible; however,
      future studies must be undertaken to identify the growth factors required for a
      permanent culture of sponge cells.

PMID- 8528500
TI  - Establishment of immortalized alveolar type II epithelial cell lines from adult
      rats.
AB  - We developed methodology to isolate and culture rat alveolar Type II cells under
      conditions that preserved their proliferative capacity, and applied lipofection
      to introduce an immortalizing gene into the cells. Briefly, the alveolar Type II
      cells were isolated from male F344 rats using airway perfusion with a pronase
      solution followed by incubation for 30 min at 37 degrees C. Cells obtained by
      pronase digestion were predominantly epithelial in morphology and were positive
      for Papanicolaou and alkaline phosphatase staining. These cells could be
      maintained on an extracellular matrix of fibronectin and Type IV collagen in a
      low serum, insulin-supplemented Ham's F12 growth medium for four to five
      passages. Rat alveolar epithelial cells obtained by this method were transformed
      with the SV40-T antigen gene and two immortalized cell lines (RLE-6T and RLE-6TN)
      were obtained. The RLE-6T line exhibits positive nuclear immunostaining for the
      SV40-T antigen and the RLE-6TN line does not. PCR analysis of genomic DNA from
      the RLE-6T and RLE-6TN cells demonstrated the T-antigen gene was present only in
      the RLE-6T line indicating the RLE-6TN line is likely derived from a spontaneous
      transformant. After more than 50 population doublings, the RLE-6T cells stained
      positive for cytokeratin, possessed alkaline phosphatase activity, and contained
      lipid-containing inclusion bodies (phosphine 3R staining); all characteristics of
      alveolar Type II cells. The RLE-6TN cells exhibited similar characteristics
      except they did not express alkaline phosphatase activity. Early passage RLE-6T
      and 6TN cells showed a near diploid chromosome number.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8528502
TI  - Divergent regulation of proteoglycan and glycosaminoglycan free chain expression
      in human keratinocytes and melanocytes.
AB  - Keratinocytes and melanocytes, which together form units of structure and
      function within human epidermis, are known to differ in expression of autocrine
      growth factors, particularly those with heparin binding affinity. Because such
      cytokines could be regulated by the endogenous heparinlike glycosaminoglycan,
      heparan sulfate, proteoglycan synthesis was compared between human keratinocytes
      and melanocytes cultured from a common donor. Following steady-state isotopic
      labeling under conditions of active growth (low density cultures) and growth
      inhibition (high density cultures), the sulfated polymers were isolated from
      conditioned media and cell extracts. We found that keratinocytes produced
      substantially more sulfated glycosaminoglycans than did the melanocytes. There
      was no evidence for hyaluronic acid synthesis by the melanocytes. The majority of
      [35S]-sulfate labeling was in the heparan sulfates of the keratinocytes and in
      the chondroitin sulfates of the melanocytes. During the transition from active
      growth to growth inhibition, there was increased heparan sulfate proteoglycan and
      free chain synthesis by keratinocytes but not by melanocytes, and chondroitin
      sulfate proteoglycan production declined in both cell lineages. The differences
      may reflect divergent evolution as each cell type came to exploit those complex
      polysaccharides in different ways to regulate molecular pathways of growth and
      differentiation. The coupling of growth inhibition with augmented synthesis of
      heparan sulfates observed for the keratinocytes suggests a regulatory role in
      growth factor signaling in that cell type.

PMID- 8528503
TI  - In vitro growth of corpora allata from Diploptera punctata.
AB  - An in vitro organ culture system was established to support growth of corpora
      allata from the cockroach Diploptera punctata. During a 1-wk incubation in L-15B
      medium supplemented with 10% fetal bovine serum (FBS) and 10% cockroach
      hemolymph, adult male corpora allata exhibited a cycle of de novo DNA synthesis
      followed by cell division. The number of S-phase cells and metaphase cells per
      corpus allatum were counted from whole-mount monolayers after labeling in vitro
      with 5'-bromo-2'-deoxyuridine and exposure to colchicine, respectively. While
      both FBS and cockroach hemolymph were essential for proliferation of allatal
      cells, the growth-promoting effect of insect hemolymph was not species-specific
      and adult female hemolymph was more potent than hemolymph from adult males.
      Furthermore, DNA synthesis of corpus allatum cells was stimulated in vitro by 20
      hydroxyecdysone. This sensitive assay system will be of immense utility in the
      search for allatal growth factors.

PMID- 8528504
TI  - Cell cycle analysis of synchronized Chinese hamster cells using bromodeoxyuridine
      labeling and flow cytometry.
AB  - Chinese hamster ovary cells were synchronized into purified populations of viable
      G1-, S-, G2-, and M-phase cells by a combination of methods, including growth
      arrest, aphidicolin block, cell cycle progression, mitotic shake-off, and
      centrifugal elutriation. The DNA content and bromodeoxyuridine (BrdUrd) labeling
      index were measured in each purified fraction by dual-parameter flow cytometry.
      The cell cycle distributions determined from the DNA measurements alone (single
      parameter) were compared with those calculated from both DNA and BrdUrd data
      (dual parameter). The results show that highly purified cells can be obtained
      using these methods, but the assessed purity depends on the method of cell cycle
      analysis. Using the single versus dual parameter measurement to determine cell
      cycle distributions gave similar results for most phases of the cell cycle,
      except for cells near the transition from G1- to S-phase and S- to G2-phase.
      There the BrdUrd labeling index determined by flow cytometry was more sensitive
      for detecting small amounts of DNA synthesis. As an alternative to flow
      cytometry, a simple method of measuring BrdUrd labeling index on cell smears was
      used and gave the same result as flow cytometry. Measuring both DNA content and
      DNA synthesis improves characterization of synchronized cell populations,
      especially at the transitions in and out of S-phase, when cells are undergoing
      dramatic shifts in biochemical activity.

PMID- 8528505
TI  - Antisense oligonucleotides to CRABP I and II alter the expression of TGF-beta 3,
      RAR-beta, and tenascin in primary cultures of embryonic palate cells.
AB  - The cellular retinoic acid-binding proteins (CRABPs) are thought to modulate the
      responsiveness of cells to retinoic acid (RA). We have previously shown that
      primary cultures of murine embryonic palate mesenchymal (MEPM) cells express both
      CRABP-I and CRABP-II genes and that this expression is regulated by RA and
      transforming growth factor beta (TGF-beta). These cells also express high levels
      of TGF-beta 3, which is also regulated by RA and TGF-beta. We have used an
      antisense strategy to investigate the role of the CRABPs in retinoid-induced gene
      expression. Subconfluent cultures of MEPM cells were treated for several days
      with phosphorothioate modified 18-mer oligonucleotides antisense to CRABP-I or
      CRABP-II and then with all-trans-retinoic acid at a concentration of 3.3 microM
      or 0.33 microM for 5 or 22 h. Total RNA was then extracted and the expression of
      TGF-beta 3, retinoic acid receptor beta (RAR-beta), and tenascin was assessed by
      northern blot analysis. Antisense oligonucleotides to CRABP-I partially inhibited
      the RA-induced TGF-beta 3, RAR-beta, and tenascin mRNA expression. The
      corresponding mis-sense oligonucleotides were without effect. Antisense
      oligonucleotides to CRABP-II also partially inhibited RA-induced expression of
      these genes. As with the CRABP-I antisense, mis-sense oligonucleotides to CRABP
      II had no effect. These data suggest that both CRABPs modulate the responsiveness
      of MEPM cells to retinoic acid. Inhibition of endogenous CRABP expression renders
      MEPM cells less responsive to RA with respect to induction of TGF-beta 3, RAR
      beta, and tenascin gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528506
TI  - Fibroblast growth factor stimulates the gene expression and production of tissue
      inhibitor of metalloproteinase-1 in bovine granulosa cells.
AB  - The hormonal control of tissue inhibitor of metalloproteinase-1 (TIMP-1) gene
      expression and production by growth factors, gonadotrophins, and serum factors in
      cultured bovine granulosa cells (BGC) were investigated. Confluent cultures of
      BGC were exposed to various factors in a defined medium and levels of TIMP-1 in
      the conditioned medium were determined by enzyme immunoassay. Basic fibroblast
      growth factor (bFGF) and acidic fibroblast growth factor (aFGF) showed potent
      stimulation of cell proliferation and TIMP-1 production by BGC, while insulin
      stimulated growth but not TIMP-1 production. Basic FGF stimulated TIMP-1
      production and BGC cell proliferation in a dose-dependent manner. A time course
      of TIMP-1 production showed substantially increased levels between 18 and 24 h in
      both control and bFGF-stimulated BGC cultures with bFGF-stimulated cultures
      having markedly higher TIMP-1 production at all time points. Consistent with the
      TIMP-1 production data, bFGF and aFGF increased the expression of TIMP-1 mRNA as
      determined by northern blot analysis, while insulin, inhibited TIMP-1 mRNA
      levels. These results indicate that FGF-induced TIMP-1 production by BGC may
      support bovine embryo development in vitro.

PMID- 8528507
TI  - Hair follicle elongation in vitro of whole skin pieces from mice.

PMID- 8528508
TI  - Stimulation of endothelial cell growth by myxalin.

PMID- 8528509
TI  - Mutation of gene required for cell spreading is corrected by serum or factor
      secreted by normal cells.

PMID- 8528510
TI  - Canine and equine mesangial cells in vitro.

PMID- 8528511
TI  - DNA fragmentation and CEA production in collagen gel culture of human colon
      carcinoma cells.

PMID- 8528512
TI  - Growth rate, labeling index, and radiation survival of cells grown in the
      Matrigel thread in vitro tumor model.
AB  - Six rodent cell lines (36B10 rat glioma cells, 9L rat gliosarcoma cells, V79
      Chinese hamster lung fibroblasts, EMT6/UW and EMT6/Ro mouse mammary sarcoma
      cells, and RIF-1 mouse fibrosarcoma cells) were tested for growth in cylindrical
      threads of Matrigel. These cells grew in the threads with doubling times of 17-23
      h, reaching maximum cell densities on the order of 10(8) cells/ml. Histological
      sections of these threads showed a heterogeneous cell distribution: cells grew to
      confluence at the thread surface and at somewhat lower cell densities in the
      thread core. [H-3]thymidine labeling index and radiation sensitivity were
      measured for 9L and EMT6/UW cells in Matrigel threads. For both cell types, the
      labeling index in Matrigel was lower than observed in cell monolayers, with
      higher labeling indexes at the thread periphery than in the thread core. When
      these threads were grown in stirred medium, lower thread diameters, higher cell
      yields per thread, and higher labeling indices were obtained. EMT6 cell
      monolayers coated with Matrigel were less radiosensitive than cells in uncoated
      monolayers. This protective effect was eliminated by irradiating in the presence
      of 1 mg/ml misonidazole. EMT6 cells consume nearly three times as much oxygen
      (mole/cm3-sec) as do 9L cells, which are equally radiosensitive in monolayers
      with or without a Matrigel coating. The radiation sensitivity of EMT6/UW cells in
      Matrigel threads was similar to that for monolayers of plateau phase cells,
      whereas for 9L cells, the response in threads was more similar to exponentially
      growing cells. We conclude that Matrigel threads provide an alternative in vitro
      model for studying the radiation response of cells in a three-dimensional
      geometry.

PMID- 8528513
TI  - Viability, attachment efficiency, and xenobiotic metabolizing enzyme activities
      are well maintained in EDTA isolated rat liver parenchymal cells after
      hypothermic preservation for up to 3 days in University of Wisconsin solution.
AB  - Rat liver parenchymal cells were isolated by EDTA perfusion and were subsequently
      purified by Percoll centrifugation. The freshly isolated liver cells had a mean
      viability of 95% as judged by trypan blue exclusion. Isolated liver parenchymal
      cells were then stored at 0 degrees C for up to 1 wk in University of Wisconsin
      solution (UW). During this hypothermic preservation, the viability was only
      slightly reduced to 92% after 1 d and to 85% after 3 d at 0 degrees C.
      Thereafter, the viability decreased rapidly. After cold storage for up to 3 d, it
      was possible to use the parenchymal liver cells either in short-term suspension
      or in cell culture. The attachment efficiency in cell culture was the same for
      freshly isolated liver cells (84%) and after 2 d cold preservation (81%). The
      cytochrome P450 content and the enzyme activities of soluble epoxide hydrolase,
      UDP-glucuronosyl transferase, phenol sulfotransferase, and glutathione S
      transferase were not significantly different between freshly isolated cells and
      cells after 3 d of hypothermic preservation. Furthermore, freshly isolated and
      intact liver cells stored for 3 d were used in the cell-mediated Salmonella
      mutagenicity test as a metabolizing system. Both fresh and stored liver
      parenchymal cells metabolized benzo(a)pyrene,2-aminoanthracene, and
      cyclophosphamide to their ultimate mutagens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528514
TI  - Actin isoform and alpha 1B-adrenoceptor gene expression in aortic and coronary
      smooth muscle is influenced by cyclical stretch.
AB  - The occurrence of vascular domains with specific biological and pharmacological
      characteristics suggests that smooth muscle cells in different arteries may
      respond differentially to a wide range of environmental stimuli. To determine if
      some of these vessel-specific differences may be attributable to mechano
      sensitive gene regulation, the influence of cyclical stretch on the expression of
      actin isoform and alpha 1B-adrenoceptor genes was examined in aortic and coronary
      smooth muscle cells. Cells were seeded on an elastin substrate and subjected to
      maximal stretching (24% elongation) and relaxation cycles at a frequency of 120
      cycles/min in a Flexercell strain unit for 72 h. Total RNA was extracted and
      hybridized to radiolabeled cDNA probes to assess gene expression. Stretch caused
      a greater reduction of actin isoform mRNA levels in aortic smooth muscle cells as
      compared to cells from the coronary artery. Steady-state mRNA levels of alpha 1B
      adrenoceptor were also decreased by cyclical stretch in both cell types but the
      magnitude of the response was greater in coronary smooth muscle cells. No changes
      in alpha 1B-adrenoceptor or beta/gamma-actin steady-state mRNA levels were
      observed in H4IIE cells, a nonvascular, immortalized cell line. The relative gene
      expression of heat shock protein 70 was not influenced by the cyclic stretch
      regimen in any of these cell types. These results suggest that stretch may
      participate in the regulation of gene expression in vascular smooth muscle cells
      and that this response exhibits some degree of cell-specificity.

PMID- 8528515
TI  - Perfused transcapillary smooth muscle and endothelial cell co-culture--a novel in
      vitro model.
AB  - As most in vitro endothelial cell (EC)-vascular smooth muscle cell (SMC) co
      culture studies have been performed utilizing static culture conditions, none
      have successfully mimicked the physical environment of these cells in vivo. EC
      covering the inner surface of blood vessels are continuously exposed to a
      hemodynamically imposed mechanical stress resulting from the flow of blood, while
      SMC are affected by pressure, a flow-related force acting perpendicular to the
      surface. We have developed a perfused transcapillary co-culture system that
      permits the chronic exposure of EC and SMC to physiological shear stresses and
      pressures. SMC and EC co-cultures were successfully established and maintained in
      long-term culture (7 wk) on an enclosed perfused bundle of semipermeable
      polypropylene capillaries. By altering flow rate and/or viscosity, shear stresses
      of 0.07-20 dyn/cm2 can be readily achieved in this system. Electron microscopic
      analysis revealed that SMC formed multilayers around the outside of the
      capillaries, whereas EC, subjected to 3 dyn/cm2 shear stress, formed an intact
      closely adherent monolayer lining the capillary lumen. EC and SMC exhibited
      characteristic ultrastructural and gross morphology. EC were separated from SMC
      by the capillary wall (pore size 0.5 microns, width 150 microM) and while no
      direct cell-cell contact was evident some cells were seen to migrate into the
      capillary wall. Both EC and SMC are exposed to the same culture medium, allowing
      the interaction of substances released in both directions. Yet separate
      populations of cells are maintained and can be individually harvested for further
      analysis. This co-culture system that mimics the architecture and physical
      environment of the vessel wall should have many potential applications in
      vascular biology.

PMID- 8528517
TI  - Epithelial cell specific properties and genetic complementation in a delta F508
      cystic fibrosis nasal polyp cell line.
AB  - Analysis of vectorial ion transport and protein trafficking in transformed cystic
      fibrosis (CF) epithelial cells has been limited because the cells tend to lose
      their tight junctions with multiple subcultures. To elucidate ion transport and
      protein trafficking in CF epithelial cells, a polar cell line with apical and
      basolateral compartments will facilitate analysis of the efficacy of different
      gene therapy strategies in a "tight epithelium" in vitro. This study investigates
      the genotypic and phenotypic properties of a CF nasal polyp epithelial, delta
      F508 homozygote, cell line that has tight junctions pre-crisis. The cells (sigma
      CFNPE14o-) were transformed with an origin-of-replication defective SV40 plasmid.
      They develop transepithelial resistance in Ussing chambers and are defective in
      cAMP-dependent Cl- transport as measured by efflux of radioactive Cl-, short
      circuit current (Isc), or whole-cell patch clamp. Stimulation of the cells by
      bradykinin, histamine, or ATP seems to activate both K(+)- and Ca(+2)-dependent
      Cl- transport. Measurement of 36Cl- efflux following stimulation with A23187 and
      ionomycin indicate a Ca(+2)-dependent Cl- transport. Volume regulatory capacity
      of the cells is indicated by cell swelling conductance. Expression of the CF
      transmembrane conductance regulator mRNA was indicated by RT-PCR amplification.
      When cells are grown at 26 degrees C for 48 h there is no indication of cAMP
      dependent Cl- as has been previously indicated in heterologous expression
      systems. Antibodies specific for secretory cell antigens indicate the presence of
      antigens found in goblet, serous, and mucous cells; in goblet and serous cells;
      or in goblet and mucous cells; but not antigens found exclusively in mucous or
      serous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528516
TI  - Morphologic, immunologic, biochemical, and cytogenetic characteristics of the
      human glioblastoma-derived cell line, SNB-19.
AB  - Human glioma-derived cell cultures and lines have proven to be of significant
      value in the study of the basic properties that contribute to the highly
      malignant, invasive and angiogenic phenotype of glioblastoma multiforme tumors.
      It is frequently difficult to establish lines that retain glial tumor properties
      in long term culture. The SNB-19 cell line has maintained and exhibited
      properties of transformation, differentiation, autocrine growth response, and
      tumorigenesis while remaining in culture for over 13 yr and undergoing over 200
      passages. This human line has been utilized in a wide range of studies related to
      the basic properties of human glioblastoma multiforme. In this report, we
      summarize the immunologic, biochemical, and cytogenetic properties of this
      versatile cell line and its utility for additional mechanistic investigation into
      the pathophysiology of the progression of human malignant gliomas.

PMID- 8528518
TI  - Growth of human tumor cell lines in transferrin-free, low-iron medium.
AB  - Iron is essential for tumor cell growth. Previous studies have demonstrated that
      apart from transferrin-bound iron uptake, mammalian cells also possess a
      transport system capable of efficiently obtaining iron from small molecular
      weight iron chelates (Sturrock et al., 1990). In the present study, we have
      examined the ability of tumor cells to grow in the presence of low molecular
      weight iron chelates of citrate. In chemically defined serum-free medium, most
      human tumor cell lines required either transferrin (5 micrograms/ml) or a higher
      concentration of ferric citrate (500 microM) as an iron source. However, we have
      also found that from 13 human cell lines tested, 4 were capable of long-term
      growth in transferrin-free medium with a substantially lower concentration of
      ferric citrate (5 microM). When grown in medium containing transferrin, both
      regular and low-iron dependent cell lines use transferrin-bound iron. Growth of
      both cell types in transferrin medium was inhibited to a certain degree by
      monoclonal antibody 42/6, which specifically blocks the binding of transferrin to
      the transferrin receptor. On the contrary, growth of low-iron dependent cell
      lines in transferrin-free, low-iron medium (5 microM ferric citrate) could not be
      inhibited by monoclonal antibody 42/6. Furthermore, no autocrine production of
      transferrin was observed. Low-iron dependent cell lines still remain sensitive to
      iron depletion as the iron(III) chelator, desferrioxamine, inhibited their
      growth. We conclude that low-iron dependent tumor cells in transferrin-free, low
      iron medium may employ a previously unknown mechanism for uptake of non
      transferrin-bound iron that allows them to efficiently use low concentrations of
      ferric citrate as an iron source. The results are discussed in the context of
      alternative iron uptake mechanisms to the well-characterized receptor-mediated
      endocytosis process.

PMID- 8528519
TI  - Removal of sialic acid from the surface of human MCF-7 mammary cancer cells
      abolishes E-cadherin-dependent cell-cell adhesion in an aggregation assay.
AB  - MCF-7 human breast cancer cells express E-cadherin and show, at least in some
      circumstances, E-cadherin-dependent cell-cell adhesion (Bracke et al., 1993). The
      MCF-7/AZ variant spontaneously displays E-cadherin-dependent fast aggregation; in
      the MCF-7/6 variant, E-cadherin appeared not to be spontaneously functional in
      the conditions of the fast aggregation assay, but function could be induced by
      incubation of the suspended cells in the presence of insulinlike growth factor I
      (IGF-I) (Bracke et al., 1993). E-cadherin from MCF-7 cells was shown to contain
      sialic acid. Treatment with neuraminidase was shown to remove this sialic acid,
      as well as most of the sialic acid present at the cell surface. Applied to MCF
      7/AZ, and MCF-7/6 cells, pretreatment with neuraminidase abolished spontaneous as
      well as IGF-I induced, E-cadherin-dependent fast cell-cell adhesion of cells in
      suspension, as measured in the fast aggregation assay. Treatment with
      neuraminidase did not, however, inhibit the possibly different, but equally E
      cadherin-mediated, process of cell-cell adhesion of MCF-7 cells on a flat plastic
      substrate as assessed by determining the percentage of cells remaining isolated
      (without contact with other cells) 24 h after plating.

PMID- 8528521
TI  - Removing salivary gland stones.

PMID- 8528520
TI  - Steroidal and growth factor regulation of [3H]thymidine incorporation by cultured
      endosalpingeal cells of the bovine oviduct.
AB  - Cultured cells from the bovine endosalpinx were used to evaluate effects of
      estradiol-17 beta, progesterone, epidermal growth factor, and insulinlike growth
      factors I and II on [3H]thymidine incorporation. Cells were treated with hormones
      and growth factors when approximately 50% confluent. After 24 h, DNA synthesis
      was quantified by pulsing cells with [3H]thymidine for 12 h and determining
      uptake into DNA. Cells prepared by mechanical dispersal incorporated more
      [3H]thymidine than cells dispersed with collagenase. However, hormonal responses
      were the same for both types of cells. As compared to plastic, cells on a
      Matrigel substratum exhibited lower incorporation of [3H]thymidine and were
      unresponsive to hormones. Estradiol-17 beta increased [3H]thymidine incorporation
      slightly at 10(-10) mol/liter and higher. Epidermal growth factor, insulinlike
      growth factor-I, and insulinlike growth factor-II also stimulated [3H]thymidine
      incorporation. Effects of insulinlike growth factor-I were greater for cells
      treated with estradiol-17 beta. In the absence of estradiol, progesterone
      inhibited [3H]thymidine incorporation at 1, 10, and 100 ng/ml. When estradiol-17
      beta was present, progesterone stimulated [3H]thymidine incorporation at 1 ng/ml
      and reduced incorporation at 100 ng/ml. In conclusion, [3H]thymidine
      incorporation by cultured oviductal endosalpingeal cells can be regulated by
      ovarian steroids and growth factors. These molecules may represent signals
      through which the ovary, embryo, and oviduct regulate oviductal growth.

PMID- 8528522
TI  - The unit training director.

PMID- 8528523
TI  - Whither the educational supervisor?
AB  - The role of an 'educational supervisor' encompasses many different functions;
      teacher, programme coordinator, assessor of competence, mentor, career adviser,
      appraiser and counsellor. Is it possible, or desirable, for one consultant to
      claim proficiency in all these areas?

PMID- 8528524
TI  - Fibromyalgia syndrome and psychiatric disorder.
AB  - Fibromyalgia syndrome (FMS) is characterised by generalised aches, pains, tender
      points, stiffness and fatigue, yet, despite increasing recognition of this
      syndrome as a clinical entity, its aetiology remains obscure. There is now
      increasing evidence that FMS represents a distinct rheumatic disorder and should
      not be regarded as a somatic illness secondary to psychiatric disorder.

PMID- 8528525
TI  - Outpatient endometrial biopsy: the pipelle.
AB  - The pipelle endometrial biopsy (EB) is accurate, safe, economical and acceptable
      to patients, clinicians and pathologists. Transvaginal sonography can reduce the
      number of EBs needed, and when both techniques are used together the sensitivity
      and specificity in the diagnosis of endometrial adenocarcinoma reach 100%.
      Hysteroscopy and dilatation and curettage are indicated in the minority of
      patients under the age of 40 years.

PMID- 8528526
TI  - Anaesthesia for day-case surgery.
AB  - With the current expansion of day surgery, many patients scheduled for elective
      surgery in British hospitals will receive their treatment on a day basis. Day
      case anaesthesia exerts a profound effect on the success and feasibility of day
      case surgery. Inpatient anaesthetic techniques are not always the most suitable
      in this area where even minor morbidity is important. This article examines the
      differences between inpatient and day-case anaesthesia, and makes a case for the
      increased recognition of the special requirements of the day-case patient.

PMID- 8528527
TI  - Endocrinology of the neonate.
AB  - Endocrine disease in the neonate is uncommon, but, if it is not promptly
      recognised and treated, may be life-threatening or have profound long-term
      consequences. This article covers congenital adrenal hyperplasia, hypothyroidism,
      neonatal thyrotoxicosis and hypopituitarism. Other endocrine problems with which
      the MRCP(Paeds) candidate should be familiar are also listed.

PMID- 8528528
TI  - Eisenmenger's syndrome and problems with anaesthesia.

PMID- 8528529
TI  - Management of profound hypothermia.
AB  - Profound hypothermia, defined as a core temperature of less than 28 degrees C, is
      a life-threatening situation associated with high mortality. Causes of severe
      hypothermia are prolonged exposure to cold air, water or snow. Initial basic life
      support and correct decisions to further therapeutic management are crucial for
      the patient's outcome.

PMID- 8528530
TI  - Insight and adherence to treatment in psychotic disorders.
AB  - Patients with psychotic disorders may benefit from strategies designed to improve
      their adherence to treatment. The assessment of relevant treatment and patient
      related variables is an important consideration for the mental health
      professional.

PMID- 8528531
TI  - Gallstone ileus following endoscopic sphincterotomy.

PMID- 8528532
TI  - Delusional misidentification of the self.

PMID- 8528533
TI  - Economy, effectiveness and efficiency in the NHS.
AB  - Any body which has been audited must make real and appropriate efforts to ensure
      that the three Es (economy, efficiency and effectiveness), as assessed by the
      auditors, are being maintained. This article looks at the importance of
      consideration of the three Es within the NHS.

PMID- 8528534
TI  - Doctors and their careers: the future.

PMID- 8528535
TI  - Doctors and their careers: the future?

PMID- 8528536
TI  - Airway management in Ludwig's angina.

PMID- 8528537
TI  - Hospital accreditation programmes: some international perspectives.

PMID- 8528538
TI  - Best practice in the health sector.

PMID- 8528539
TI  - Prospects for newer technologies in cervical cancer screening programmes.
AB  - Because of the limitations of the Pap smear test, much attention has been given
      to development of technologies to increase the reliability of routine cervical
      cytology. Newer technologies in this field include automated slide preparation
      devices, automated slide readers, direct visualization methods and application of
      flow cytometry and nuclear magnetic resonance. These technologies show promise,
      but data on their costs, efficacy and effectiveness remain limited. Their
      introduction in Australia should be linked to local trials, and consideration of
      their impact on mortality and morbidity and on health care budgets.

PMID- 8528540
TI  - Quality pays and reduces your risk.
AB  - The Royal Victorian Eye and Ear Hospital has an active campaign of quality. All
      departments and all staff are imbued with the spirit of total quality management
      (TQM). They regularly ask themselves, 'What am I doing now that I can do better?'
      The hospital has demonstrated savings of more than $3 m over 5 years through
      improved quality activities. This has led to better quality outcomes for its
      patients. It has reduced its risk factors and is well placed to survive
      expenditure cuts.

PMID- 8528541
TI  - Surgical audit in private practice.
AB  - Surgical audit in private practice is not only simple to perform but is very
      rewarding. It is intellectually stimulating and inevitably improves outcome.
      Computer literacy is helpful though not essential.

PMID- 8528542
TI  - Paediatric hospital services: are we satisfying our adolescent patients?
AB  - This study evaluated the satisfaction of adolescents with general inpatient
      services in a paediatric hospital. The results suggest that the adolescents were
      generally satisfied with the services provided. However, a number of concerns
      were expressed about the physical characteristics of the wards, the day to day
      organization of the wards, and the lack of opportunity to participate in
      treatment planning. The results also suggest that adolescents' satisfaction with
      inpatient services will be improved if more attention is given to the physical
      surroundings in hospital wards and the level of privacy afforded to adolescent
      inpatients. Finally, the results draw attention to the importance adolescents
      place on being involved in decisions about their treatment planning. There is a
      great need for studies which focus on adolescents' perceptions of health
      services. This will help to ensure that adolescents receive services they
      perceive to be relevant and effective.

PMID- 8528543
TI  - The efficacy of staff training on improving internal customer satisfaction in a
      rural health setting.
AB  - The NSW Health Department is 3 years into its customer satisfaction initiative.
      North West Health Service, one of the largest rural health districts, was among
      the first centres to embrace the customer satisfaction philosophy starting with
      compulsory training of all staff. This paper reports on changes in staff morale
      (internal satisfaction) as a result of that training. The data suggest that
      training per se has had minimal effect and argues for management development,
      particularly regarding leadership, rather than fiscal skills.

PMID- 8528544
TI  - Continuous quality improvement in a day ward.
AB  - The increasing usage of short-stay facilities within Australia has focused
      attention upon the efficiency of surgical day wards. Although the Australian
      Council on Healthcare Standards (ACHS) is actively promoting the development of
      clinical indicators for same-day facilities, there is a concern that these
      measurements relate to efficiency rather than to humanitarian aspects of the
      quality of service. We have established a programme of continuous quality
      improvement (CQI) in a surgical day ward with the nursing and clerical staff
      being empowered as core members of the team. Reviews and audits have identified a
      number of targets for our activity. Some issues have been resolved very easily
      (ward clerks telephoning patients to confirm admissions the next day) but the
      solution to some other problems has required lengthy negotiations between various
      groups (the construction of clearly written pre-admission guidelines for
      patients). Activities aimed at improving the service provided to patients
      attending surgical day wards must extend beyond the mere collection of
      information about clinical indicators.

PMID- 8528545
TI  - Errors in drug prescribing.
AB  - This study reports on early results following the introduction of one measure of
      medication prescription errors, that being the prescribing of a drug for which
      there is an 'alert' notice, into The Australian Council on Healthcare Standards
      Accreditation process. Characteristics of hospitals reporting of zero and non
      zero errors were analysed using a logistic model. After adjusting for other
      hospital characteristics and duration of data collection, hospitals over 100 beds
      were more likely to report medication errors compared to hospitals with 1-100
      beds. Reporting of these prescribing errors was not associated with the
      particular type or location of the hospital. However, as a result of monitoring
      of this indicator, a number of hospitals reported an increase in their quality
      assurance activities. It is a sentinel event and not a rate based indicator and,
      as a performance measure, is of greater value as an internal, rather than
      external, review mechanism.

PMID- 8528546
TI  - Enhancing effect of staurosporine on NO production in rat peritoneal macrophages
      via a protein kinase C-independent mechanism.
AB  - Staurosporine (3-100 nM), frequently used as a protein kinase C (PKC) inhibitor,
      increased accumulation of nitrite in the culture medium of rat peritoneal
      macrophages up to 6 times above the control level. Moreover, when used in
      combination with the stable analogue of cyclic AMP, dibutyrylcyclic AMP (db
      cyclic AMP; 0.1 mM), and/or a cytokine, tumour necrosis factor-alpha (TNF alpha;
      100 u ml-1), staurosporine synergistically potentiated, up to 30 times, nitrite
      accumulation. On the other hand, the other PKC inhibitors, calphostin C and H-7
      (10 nM-10 microM) were not effective under the same conditions. The staurosporine
      induced nitrite accumulation, in both the presence and the absence of TNF alpha
      and/or db cyclic AMP was effectively inhibited by the protein synthesis
      inhibitor, cycloheximide, or by the nitric oxide (NO) synthesis inhibitor, NG
      monomethyl-L-arginine (L-NMMA). Thus our data suggest that staurosporine may
      enhance NO production in macrophages via intracellular mechanisms unrelated to
      the PKC inhibition.

PMID- 8528547
TI  - Protective effect of NO on gastric lesions and inhibition of expression of
      gastric inducible NOS by flurbiprofen and its nitro-derivative,
      nitroflurbiprofen.
AB  - Nitroflurbiprofen (NFP) causes significantly less gastric lesions than
      flurbiprofen (FP), probably because of its capacity to release nitric oxide (NO)
      in the stomach. Lipopolysaccharide (LPS), which induces the expression of an
      inducible type of NO synthase (iNOS) in rat stomach, also reduces gastric mucosal
      damage elicited by FP. Furthermore, both FP and NFP decrease significantly the
      amount of mRNA encoding iNOS induced by LPS in the stomach. The inhibitory effect
      of NFP seems to be due at least in part to its ability to release NO.

PMID- 8528548
TI  - Evidence that 5-HT1D receptors mediate inhibition of sympathetic ganglionic
      transmission in anaesthetized cats.
AB  - In anaesthetized cats, 5-carboxamidotryptamine (5-CT) or 5-hydroxytryptamine (5
      HT) (0.3-300 micrograms kg-1,i.v.) inhibited the postganglionic compound action
      potential evoked by preganglionic electrical stimulation (0.5 Hz) with a similar
      potency in the stellate and splanchnic ganglia. In the 5-HT experiments
      transmission thorough the inferior mesenteric ganglia was also recorded. The
      maximal inhibitory effect of 5-HT was greater on the stellate and splanchnic
      ganglia (60 +/- 4 and 52 +/- 5%) than on the inferior mesenteric (15 +/- 2%). The
      effects of 5-HT were unaffected by pretreatment with antagonists (1 mg kg-1;i.v.)
      for 5-HT2 (BW501C67), 5-HT1A (WAY-100635) and 5-HT3 receptors (ondansetron).
      However, responses to both 5-HT and 5-CT were attenuated significantly by
      GR127935 (1 mg kg-1) except the responses to 5-HT at the inferior mesenteric
      ganglia. These results are consistent with the involvement of 5-HT1D receptors
      mediating inhibition of sympathetic ganglionic transmission in vivo.

PMID- 8528549
TI  - Enhancement of the hypotensive and vasodilator effects of endotoxaemia in
      conscious rats by the endothelin antagonist, SB 209670.
AB  - In conscious, chronically-instrumented rats, the non-selective endothelin
      antagonist, SB 209670 (10 micrograms kg-1 min-1), caused marked enhancement of
      the fall in mean arterial blood pressure during infusion of lipopolysaccharide
      (LPS) for 24 h (LPS alone = -6 +/- 3 mmHg; LPS+SB 209670 = -30 +/- 2 mmHg). This
      effect was accompanied by a conversion of the mesenteric vasoconstriction to a
      substantial mesenteric vasodilatation and an augmentation of the hindquarters
      vasodilatation, seen with LPS alone. Notably, the marked renal hyperaemic
      vasodilatation during LPS infusion was not affected significantly by SB 209670.
      These results indicate that endothelin, directly and/or indirectly, plays a
      pivotal role in the cardiovascular sequelae of endotoxaemia in conscious rats,
      and prevents marked hypotension, particularly by opposing mesenteric
      vasodilatation.

PMID- 8528550
TI  - Reduction by NG-nitro-L-arginine methyl ester (L-NAME) of antigen-induced nasal
      airway plasma extravasation in human subjects in vivo.
AB  - In non-allergic subjects, histamine induced a reduction of minimal nasal cross
      sectional area (Amin) and an increase in albumin release into nasal lavage. The
      effect of histamine on albumin release was inhibited by pretreatment with NG
      nitro-L-arginine methyl ester (L-NAME), 1 mumol but not by D-NAME, 1 mumol. L
      NAME, 1 and 10 mumol, did not inhibit the histamine-induced reduction of Amin. In
      subjects allergic to grass pollen, antigen challenge induced a reduction in Amin
      that was not changed by pretreatment with L-NAME, and an increase in albumin
      release that was inhibited by L-NAME, 1 mumol. The data support a role for nitric
      oxide in mediating plasma extravasation in the nose induced by antigen challenge
      or histamine.

PMID- 8528551
TI  - Relationship between agonist binding, phosphorylation and immunoprecipitation of
      the m3-muscarinic receptor, and second messenger responses.
AB  - 1. Phosphoinositidase C-linked m3-muscarinic receptors expressed in Chinese
      hamster ovary cells (CHO-m3 cells) are phosphorylated on serine following agonist
      stimulation. 2. m3-Muscarinic receptor phosphorylation is concentration-dependent
      requiring a carbachol concentration of 13.2 microM for half maximal stimulation.
      3. The phosphorylation concentration-response curve lies to the left of the curve
      for carbachol binding to muscarinic receptors (KD = 100 microM) in membranes from
      CHO-m3 cells. In contrast, receptor phosphorylation closely correlates with
      receptor-mediated phosphoinositidase C activation (EC50 for inositol 1,4,5
      trisphosphate accumulation during the peak and plateau phases were 7.14 microM
      and 5.92 microM respectively) but not with rapid agonist-mediated calcium
      elevation (EC50 = 0.32 microM) measured in fura-2-AM loaded cells. 4. These data
      suggest a dissociation of receptor phosphorylation from agonist occupation. Such
      an apparent 'receptor reserve' for m3-muscarinic receptor phosphorylation may be
      indicative of a mechanism that is dependent on a small amplification of the
      receptor signal, though probably dissociated from the calcium signal.

PMID- 8528552
TI  - [3H]-RS-45041-190: a selective high-affinity radioligand for I2 imidazoline
      receptors.
AB  - 1. RS-45041-190 (4-chloro-2-(imidazolin-2-yl)isoindoline) is an I2 imidazoline
      receptor ligand with the highest affinity and selectivity so far described; [3H]
      RS-45041-190 has a tritium atom attached to the 7-position on the isoindoline
      ring. 2. [3H]-RS-45041-190 binding to rat kidney membranes was saturable (Bmax =
      223.1 +/- 18.4 fmol mg-1 protein) and of high affinity (Kd = 2.71 +/- 0.59 nM).
      Kinetic studies revealed that the binding was rapid and reversible, with [3H]-RS
      45041-190 interacting with two sites or two affinity states. 3. Competition
      studies showed that 60-70% of [3H]-RS-45041-190 binding (1 nM) was specifically
      to imidazoline binding sites of the I2 subtype, characterized by high affinity
      for idazoxan (pIC50 7.85 +/- 0.03) and cirazoline (pIC50 8.16 +/- 0.05). The
      remaining 30-40% was displaced specifically by the monoamine oxidase A
      inhibitors, clorgyline and pargyline. 4. alpha 1- and alpha 2-adrenoceptor, I1
      imidazoline, histamine, 5-hydroxytryptamine or dopamine receptor ligands had low
      affinity suggesting that [3H]-RS-45041-190 did not label receptors of these
      classes. 5. In autoradiography studies, [3H]-RS-45041-190 labelled discrete
      regions of rat brain corresponding to the distribution of I2 subtypes, notably
      the subfornical organ, arcuate nucleus, interpeduncular nucleus, medial habenular
      nucleus and lateral mammillary nucleus, and additional sites in the locus
      coeruleus, dorsal raphe and dorsomedial hypothalamic nucleus. 6. [3H]-RS-45041
      190 therefore labels I2 receptors with high affinity, and an additional site
      which has high affinity for some monoamine oxidase inhibitors.

PMID- 8528553
TI  - RS-45041-190: a selective, high-affinity ligand for I2 imidazoline receptors.
AB  - 1. RS-45041-190 (4-chloro-2-(imidazolin-2-yl)isoindoline) showed high affinity
      for I2 imidazoline receptors labelled by [3H]-idazoxan in rat (pKi = 8.66 +/-
      0.09), rabbit (pKi = 9.37 +/- 0.07), dog (pKi = 9.32 +/- 0.18) and baboon kidney
      (pKi = 8.85 +/- 0.12), but had very low affinity for alpha 2-adrenoceptors in rat
      cerebral cortex (pKi = 5.7 +/- 0.09). 2. RS-45041-190 showed low affinity for
      other adrenoceptors, dopamine, 5-hydroxytryptamine, and muscarinic receptors and
      dihydropyridine binding sites (selectivity ratio > 1000). 3. RS-45041-190 showed
      moderate potency for the inhibition of monoamine oxidase A in vitro (pIC50 =
      6.12), but had much lower potency for monoamine oxidase B (pIC50 = 4.47), neither
      of which equated with its affinity for I2 receptors. 4. RS-45041-190 (0.001 to 3
      mg kg-1, i.v. and 1 ng-50 micrograms i.c.v.) had only small, transient effects on
      blood pressure and heart rate in anaesthetized rats. In conscious rats, RS-45041
      190 had no effect on body core temperature or tail skin temperature (1 mg kg-1,
      s.c.) or on activity or rotarod performance (10 mg kg-1, i.p.). There were also
      no effects on barbiturate sleeping time in mice after doses of 1-10 mg kg-1, i.p.
      5. RS-45041-190 (10 and 25 mg kg-1, i.p.) significantly increased food
      consumption in rats for up to 4 h after dosing, but unlike idazoxan (10 mg kg-1,
      i.p.) did not increase water consumption. RS-45041-190 is therefore a selective,
      high-affinity ligand at I2 imidazoline receptors and its hyperphagic effect may
      suggest a role for I2 imidazoline receptors in the modulation of
      appetite.However, in the absence of a selective agonist it is unclear whether
      this ligand is an agonist or an antagonist at I2 receptors.

PMID- 8528554
TI  - Effects of the ETA/ETB receptor antagonist, bosentan on endothelin-1-induced
      myocardial ischaemia and oedema in the rat.
AB  - 1. The purpose of this study were to assess the role of ETB receptors in
      mediating endothelin-1 (ET-1)-induced myocardial ischaemia and oedema in rats and
      to study the inhibitory action of the novel nonpeptide ETA/ETB receptor
      antagonist, bosentan on these actions of ET-1. 2. Intravenous bolus injection of
      ET-1 (1 nmol kg-1) into anaesthetized rats produced marked ST segment elevation
      of the electrocardiogram without causing arrhythmias. ST segment elevation
      developed within 30-50 s and persisted for at least 30 min following injection of
      the peptide. 3. Pretreatment of the animals with bosentan (10 mg kg-1, i.v.)
      inhibited on average by 96% the ST segment elevation elicited by ET-1 (1 nmol kg
      1) compared to the 82% inhibition observed with the ETA receptor-selective
      antagonist, FR 139317 (2.5 mg kg-1, i.v.). 4. Bolus injection of ET-1 (1 nmol kg
      1, i.v.) to conscious chronically catheterized rats evoked a transient depressor
      response followed by a prolonged pressor effect. Corresponding to changes in
      blood pressure, a transient tachycardia and a sustained bradycardia were
      observed. ET-1 (1 nmol kg-1) enhanced albumin extravasation by 119 and 93% in the
      left ventricle and right atrium, respectively, as measured by the local
      extravascular accumulation of Evans blue dye. 5. Pretreatment of the animals with
      bosentan (10 mg kg-1) inhibited by 71 and 90% the depressor and pressor actions
      of ET-1 (1 nmol kg-1) and the accompanying tachycardia and bradycardia,
      respectively. FR 139317 (2.5 mg kg-1) attenuated the pressor response to ET-1 and
      accompanying bradycardia by 75%, without affecting the depressor action and
      accompanying tachycardia. ET-1-induced albumin extravasation was completely
      inhibited by bosentan (10 mg kg-1) both in the left ventricle and right atrium,
      compared to the 86% inhibition observed with FR 139317 (2.5 mg kg-1).6. Like ET
      1, the ETB receptor-selective agonist, IRL 1620 (0.3 and 1 nmol kg-1, i.v.) also
      produced dose-dependent ST segment elevation in anaesthetized rats and enhanced
      albumin extravasation (up to141% of control) in the left ventricle and right
      atrium, respectively, in conscious rats. These effects ofIRL 1620 were completely
      prevented by bosentan (10 mg kg-1).7. These results indicate that ETB receptors,
      albeit to a lesser extent than ETA receptors, are also involved in mediating ET-1
      induced myocardial ischaemia and oedema in the rat, and suggest the therapeutic
      potential for bosentan in the treatment of ischaemic myocardial diseases.

PMID- 8528555
TI  - Evidence that activation of 5-HT2 receptors in the forebrain of anaesthetized
      cats causes sympathoexcitation.
AB  - 1. The aim of the present experiments was to determine whether the effects of
      lateral ventricular application of 5-HT on cardiovascular and respiratory
      variables in anaesthetized cats are mediated by forebrain 5-HT2 receptors. This
      was carried out by determining whether the effects of 5-HT are blocked by the 5
      HT2 antagonist, cinanserin and if they are mimicked by the selective 5-HT2
      agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). 2. Cats were
      anaesthetized with a mixture of alpha-chloralose and pentobarbitone sodium,
      neuromuscularly blocked and artifically ventilated. The following cardiovascular
      and respiratory variables were recorded: renal, splanchnic and cardiac
      sympathetic nerve activities, phrenic nerve activity, heart rate, arterial blood
      pressure, femoral arterial conductance and tracheal pressure. All drugs were
      administered via the lateral ventricle and the action of these agonists was
      restricted to forebrain sites by a cannula placed in the Aqueduct of Sylvius. 3.
      Cumulative doses of 5-HT (10-160 nmol kg-1) and DOI (80-320 nmol kg-1) injected
      into the lateral ventricle caused significant increases in blood pressure, heart
      rate, cardiac and splanchnic sympathetic nerve activity and a decrease in femoral
      arterial conductance. DOI and 5-HT caused a greater increase in cardiac compared
      with splanchnic nerve activity and failed to change renal nerve activity. 5-HT
      but not DOI significantly increased the magnitude and the number of phrenic
      bursts as well as significantly increasing tracheal pressure. The effects of 5-HT
      also differed from DOI in that 5-HT evoked maximal pressor and near maximal
      sympathoexcitatory effects after the first dose, whereas the pressor and
      sympathoexcitatory effects of DOI were graded over the complete dose-range.4 The
      5-HT2 antagonist, cinanserin (265 nmol kg-1, i.c.v.) caused significant falls in
      blood pressure,heart rate and cardiac nerve activity and an increase in femoral
      arterial conductance. Splanchnic andrenal sympathetic nerve activity, phrenic
      nerve activity and tracheal pressure were unaffected by cinanserin. After
      pretreatment with cinanserin all cardiovascular and respiratory effects of 5-HT
      were significantly attenuated.5 It is concluded that in the cat, as DOI and 5-HT
      have similar effects on the cardiovascular variables recorded and as the effects
      of 5-HT are blocked by cinanserin, 5-HT can act on 5-HT2 receptors located in the
      forebrain to cause differential sympathoexcitation and a rise in arterial blood
      pressure. Further,the sympathoexcitatory effects mediated by 5-HT2 receptors
      located in the forebrain differ from those located in the hindbrain in that they
      mediate increases in cardiac nerve activity and heart rate and also have no
      effect on renal nerve activity.

PMID- 8528556
TI  - The in vivo effect of lipopolysaccharide on the spontaneous release of
      transmitter from motor nerve terminals.
AB  - 1. The in vivo effect of E. coli lipopolysaccharide (LPS) on the spontaneous
      release of transmitter was studied in the isolated phrenic nerve-diaphragm
      preparation of the mouse. 2. The resting membrane potential was decreased and
      frequency of miniature endplate potentials (m.e.p.ps) was increased by treatment
      with LPS. 3. Pretreatment of diaphragms with ouabain markedly increased the
      frequency of m.e.p.ps in control group but not in the LPS group. 4. When mice
      were treated with polymyxin B (a LPS neutralizer), pentoxifylline (an inhibitor
      of tumor necrosis factor-alpha formation) and NG-nitro-L-arginine (an inhibitor
      of nitric oxide (NO) synthase) the effects of LPS were reversed. 5. These results
      suggest that LPS increases the spontaneous transmitter release through, at least
      in part, the pathways of tumour necrosis factor-alpha and NO followed by an
      inhibition of the Na(+)-pump activity in the endplate area.

PMID- 8528557
TI  - Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate
      subtype of glutamate receptor in cultured hippocampal neurones.
AB  - 1. The effects of propofol (2,6 di-isopropylphenol) on responses to the selective
      glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, were
      investigated in cultured hippocampal neurones of the mouse. Whole cell and single
      channel currents were recorded by patch-clamp techniques. Drugs were applied with
      a multi-barrel perfusion system. 2. Propofol produced a reversible, dose
      dependent inhibition of whole cell currents activated by NMDA. The concentration
      of propofol which induced 50% of the maximal inhibition (IC50) was approximately
      160 microM. The maximal inhibition was incomplete leaving a residual current of
      about 33% of the control response. This inhibitory action of propofol was neither
      voltage- nor use-dependent. 3. Analysis of the dose-response relation for whole
      cell NMDA-activated currents indicated that propofol caused no significant change
      in the apparent affinity of the receptor for NMDA. 4. Outside-out patch
      recordings of single channel currents evoked by NMDA (10 microM) revealed that
      propofol (100 microM) reversibly decreased the probability of channel opening but
      did not influence the average duration of channel opening or single channel
      conductance. 5. Whole-cell currents evoked by kainate (50 microM) were
      insensitive to propofol (1 microM-1 mM). 6. These results indicate that propofol
      inhibits the NMDA subtype of glutamate receptor, possibly through an allosteric
      modulation of channel gating rather than by blocking the open channel. Depression
      of NMDA-mediated excitatory neurotransmission may contribute to the anaesthetic,
      amnesic and anti-convulsant properties of propofol.

PMID- 8528558
TI  - Effects of 5-HT receptor agonists on depolarization-induced [3H]-noradrenaline
      release in rabbit hippocampus and human neocortex.
AB  - 1. The present study attempted to determine whether noradrenaline (NA) release in
      rabbit hippocampus and human neocortex is modulated by presynaptic 5
      hydroxytryptamine (5-HT) receptors. 2. Slices of rabbit hippocampus and human
      neocortex, loaded with [3H]-noradrenaline ([3H]-NA) were superfused and the
      effects of 5-hydroxytryptamine (5-HT) receptor ligands on electrically evoked
      [3H]-NA release were investigated. 3. In rabbit hippocampus, 5-HT, 5
      carboxamidotryptamine (5-CT; 32 microM) and 2-CH3-5-HT (32 microM) increased [3H]
      NA release elicited with 360 pulses/3 Hz. Facilitation of transmitter release was
      not influenced by the 5-HT3 receptor antagonist, tropisetron but was prevented by
      the alpha 2-adrenoceptor antagonist, rauwolscine. When autoinhibition was avoided
      by stimulating the tissue with 4 pulses/100 Hz (pseudo-one pulse-(POP)
      stimulation), 2-CH3-5-HT decreased evoked transmitter release, whereas 5-HT and 5
      CT had no effect. Inhibition caused by 2-CH3-5-HT was not affected by tropisetron
      but counteracted by the alpha 2-adrenoceptor ligands, clonidine and rauwolscine.
      Inhibition caused by clonidine was diminished in the presence of 5-CT or 2-CH3-5
      HT. 4. In human neocortex, [3H]-NA release elicited with 360 pulses/3 Hz was
      increased by 10 microM 5-HT and 32 microM 5-CT, whereas 2-CH3-5-HT was
      ineffective. [3H]-NA release evoked with a modified POP stimulation (2 bursts of
      4 pulses/100 Hz, 3.5 min apart) was not affected by 2-CH3-5-HT or 5-CT. 5. The
      present results indicate that 5-HT, 2-CH3-5-HT and 5-CT can act on presynaptic
      alpha 2-autoreceptors as partial agonists (2-CH3-5-HT; in rabbit hippocampal
      tissue) or antagonists (5-HT and 5-CT; in tissue of rabbit hippocampus and human
      neocortex). Furthermore the existence of autoinhibition dictates whether these
      drugs cause facilitation of release, inhibition or have no effect.

PMID- 8528559
TI  - Mechanism of inhibition of the sodium current by bepridil in guinea-pig isolated
      ventricular cells.
AB  - 1. Effects of bepridil, a sodium-, calcium-, and potassium-antagonistic agent, on
      the Na+ current were studied by the whole cell voltage clamp technique (tip
      resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil
      produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3.
      Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization
      direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In
      the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2
      Hz, whereas changes in pulse duration did not significantly effect this use
      dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms;
      n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1
      tosylchloramide sodium, bepridil (50 mumol l-1) still showed use-dependent block
      which was independent of the holding potential. 6. The recovery time constant
      from the bepridil-induced use-dependent block was 0.48 s at holding potential of 
      100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that
      bepridil could bind to the receptor in the sodium channel through the hydrophobic
      and the hydrophilic pathway and leave the receptor through the hydrophobic
      pathway in the lipid bilayer. The binding and dissociation kinetics of this drug
      were shown to be fast, and the accumulation of the drug in the sodium channel
      appeared to be small. Bepridil is presumed to be safe in terms of adverse effects
      that result from drug-accumulation in the sodium channel.

PMID- 8528560
TI  - Evidence that the atypical 5-HT3 receptor ligand, [3H]-BRL46470, labels
      additional 5-HT3 binding sites compared to [3H]-granisetron.
AB  - 1. The radioligand binding characteristics of the 3H-derivative of the novel 5
      HT3 receptor antagonist BRL46470 were investigated and directly compared to the
      well characterized 5-HT3 receptor radioligand [3H]-granisetron, in tissue
      homogenates prepared from rat cerebral cortex/hippocampus, rat ileum, NG108-15
      cells, HEK-5-HT3As cells and human putamen. 2. In rat cerebral
      cortex/hippocampus, rat ileum, NG108-15 cell and HEK-5-HT3As cell homogenates,
      [3H]-BRL46470 bound with high affinity (Kd (nM): 1.57 +/- 0.18, 2.49 +/- 0.30,
      1.84 +/- 0.27, 3.46 +/- 0.36, respectively; mean +/- s.e. mean, n = 3-4) to an
      apparently homogeneous saturable population of sites (Bmax (fmol mg-1 protein):
      102 +/- 16, 44 +/- 4, 968 +/- 32 and 2055 +/- 105, respectively; mean +/- s.e.
      mean, n = 3-4) but failed to display specific binding in human putamen
      homogenates. 3. In the same homogenates of rat cerebral cortex/hippocampus, rat
      ileum, NG108-15 cells, HEK-5-HT3As cells and human putamen as used for the [3H]
      BRL46470 studies, [3H]-granisetron also bound with high affinity (Kd (nM): 1.55
      +/- 0.61, 2.31 +/- 0.44, 1.89 +/- 0.36, 2.03 +/- 0.42 and 6.46 +/- 2.58
      respectively; mean +/- s.e. mean, n = 3-4) to an apparently homogeneous saturable
      population of sites (Bmax (fmol mg-1 protein): 39 +/- 4, 20 +/- 2, 521 +/- 47,
      870 +/- 69 and 18 +/- 2, respectively; mean +/- s.e. mean, n = 3-4). 4.
      Competition studies with a range of structurally different 5-HT3 receptor ligands
      indicated that in both rat cerebral cortex/hippocampus and rat ileum homogenates,
      [3H]-BRL46470 binding exhibited a pharmacological profile consistent with the
      labelling the 5-HT3 receptor with compounds competing with Hill coefficients
      close to unity.5 In HEK-5-HT3As cell homogenates, [3H]-BRL46470 and [3H]
      granisetron associated rapidly((3.84+/-0.4)106 M-1S-1 and (5.85+/-0.2)106 M-1S-1,
      respectively, mean+/-s.e.mean, n=3-4) in an apparently monophasic manner.
      Following the establishment of equilibrium, both [3H]-BRL46470 and [3H]
      granisetron at a saturating concentration ([3H]-BRL46470 approximately 16 nM;
      [3H]-granisetron approximately 18 nM) and at a sub-Kd concentration
      (approximately 1 nm for both radioligands)dissociated biphasically in HEK-5-HT3As
      cell homogenates (saturating concentration; [3H]-BRL464704.05 x 10-3+/-2.53 x I0
      3 s-1 and 5.83 x 10-5+0.91 x I0-5 s-1; [3H]-granisetron 3.20 x 10-3+ 1.70 x IO-3
      s-1 and18.58 x 10-5 +/- 4.19 x I0-5 s-1: sub-Kd concentration; [3H]-BRL46470 2.47
      x 10-3+/- 1.18 x 10-3 s-1 and 9.30x 10-5+/-2.59x 10-5 S-1; [3H]-granisetron 65.91
      x 10-3+/-22.14x I0-3 s-1 and 49.96x 10-5+/-12.26x 10-5s- 1 mean+/- s.e.mean, n =
      4-8) when induced by a 300 fold dilution in ice-cold Tris/Krebs.6 In conclusion,
      the present study provides evidence that [3H]-BRL46470 specifically labels the 5
      HT3receptor in rat cerebral cortex/hippocampus, rat ileum, NG108-15 cell and HEK
      5-HT3As cell homogenates, but fails to label the 5-HT3 receptor expressed in
      human putamen. Whilst the pharmacological profile of the site labelled by [3H]
      BRL46470 is directly comparable to that labelled by [3H]-granisetron, [3H]
      BRL46470 consistently labelled approximately twice the density of sites compared
      to [3H]-granisetron in the same tissue homogenates prepared from rat
      cortex/hippocampus, ratileum, NG108-15 cells and HEK-5-HT3As cells.

PMID- 8528561
TI  - Nitric oxide, an enteric nonadrenergic-noncholinergic relaxant transmitter:
      evidence using phosphodiesterase V and nitric oxide synthase inhibition.
AB  - 1. The effects of NG-nitro-L-arginine (L-NOARG), a nitric oxide synthase
      inhibitor, and SK&F 96231, a phosphodiesterase type V inhibitor, on electrical
      field stimulated (EFS) nonadrenergic noncholinergic (NANC) relaxations of rat
      fundal strips, guinea-pig isolated ileum longitudinal muscle with intact
      myenteric plexus, and guinea-pig taenia caeci were investigated. 2. Reproducible
      repeated control random EFS frequency-response curves were obtained for all three
      tissues. 3. Depending on the frequency of stimulation, L-NOARG (10(-4)-5 x 10(-3)
      M) caused either a complete or partial inhibition of the NANC-induced relaxations
      of the rat fundal strips and the guinea-pig isolated ileum longitudinal muscle
      with intact myenteric plexus, but not of the guinea-pig taenia caeci. The
      inhibitory action of L-NOARG was partially or totally reversed, depending on the
      tissue, by L-arginine (5 x 10(-3) M). 4. SK&F 96231 (10(-6)-10(-4) M) caused a
      concentration- and frequency-dependent potentiation of both the size and duration
      of the EFS-induced NANC relaxant response of rat fundal strips and guinea-pig
      isolated ileum longitudinal muscle with intact myenteric plexus, but not of the
      guinea-pig taenia caeci. 5. Zaprinast, another phosphodiesterase type V inhibitor
      (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation of
      the NANC relaxant responses to EFS of rat fundal strips. 6. SK&F 96231 and
      zaprinast alone (10(-6)-10(-4) M) caused a concentration-dependent relaxation of
      the agonist-induced tone of all three tissues with the maximum degree of
      relaxation found to be in the order stomach < ileum < caecum. This is the reverse
      order for ability of SK&F 96231 to potentiate relaxant responses to EFS. 7. These
      results suggest NO is involved in the NANC nerve-mediated relaxation of rat
      fundal strips and guinea-pig isolated ileum longitudinal muscle with intact
      myenteric plexus, but not the guinea-pig taenia caeci.

PMID- 8528562
TI  - Activation of phospholipase C in SH-SY5Y neuroblastoma cells by potassium-induced
      calcium entry.
AB  - 1. We used SH-SY5Y human neuroblastoma cells to investigate whether
      depolarization with high K+ could stimulate inositol (1,4,5)trisphosphate
      (Ins(1,4,5)P3) formation and, if so, the mechanism involved. 2. Ins(1,4,5)P3 was
      measured by a specific radioreceptor mass assay, whilst [Ca2+]i was measured
      fluorimetrically with the Ca2+ indicator dye, Fura-2. 3. Depolarization with K+
      caused a time- and dose-dependent increase in [Ca2+]i (peak at 27 s, EC50 of 50.0
      +/- 9.0 mM) and Ins(1,4,5)P3 formation (peak at 30 s, EC50 of 47.4 +/- 1.1 mM).
      4. Both the K(+)-induced Ins(1,4,5)P3 formation and increase in [Ca2+]i were
      inhibited dose-dependently by the L-type voltage-sensitive Ca2+ channel closer,
      (R+)-BayK8644, with IC50 values of 53.4 nM and 87.9 nM respectively. 5. These
      data show a close temporal and dose-response relationship between Ca2+ entry via
      L-type voltage-sensitive Ca2+ channels and Ins(1,4,5)P3 formation following
      depolarization with K+, indicating that Ca2+ influx can activate phospholipase C
      in SH-SY5Y cells.

PMID- 8528563
TI  - Characterization of the thromboxane (TP-) receptor subtype involved in
      proliferation in cultured vascular smooth muscle cells of rat.
AB  - 1. The effects of the thromboxane A2 (TxA2)-mimetic, U-46619, on the
      proliferation of vascular smooth muscle cells (VSMCs) were examined in a clonal
      smooth muscle cell line, A10, which was derived from foetal rat aorta. 2. [3H]-U
      46619 bound to A10 cells of passages 18-20 (p18-20) with two classes of sites.
      The high affinity site showed a Bmax of 3.0 +/- 1.8 fmol mg-1 protein with a KD
      value 1.0 +/- 0.1 nM, while the low affinity site showed a Bmax of 43.0 +/- 6.0
      fmol mg-1 protein and KD value of 129.0 +/- 7.9 nM. However, [3H]-U-46619 bound
      to A10 cells from passages 28-30 (p28-30) at a single class of site with a Bmax
      111.0 +/- 9.0 fmol mg-1 protein and a KD value of 175.4 +/- 22.0 nM. 3.
      Cinnamophilin and SQ29548 inhibited specific [3H]-U-46619 binding to p18-20 A10
      cells in a concentration-dependent manner with Ki values of 390.0 +/- 3.2 and 4.6
      +/- 1.0 nM, respectively at a high affinity site, and 2.6 +/- 0.2 microM and
      310.0 +/- 6.4 nM, respectively at the low affinity site. 4. U-46619 produced
      isometric contractions of rat aorta in a concentration-dependent manner with an
      EC50 7.0 +/- 1.2 nM. Cinnamophilin and SQ29548 antagonized U-46619-induced aortic
      contractions with pA2 values 6.3 +/- 0.1 and 8.2 +/- 0.2, respectively. 5. U
      46619 increased [3H]-thymidine incorporation into DNA of p18-20 and p28-30 A10
      cells in aconcentration-dependent manner with EC50 values 362.7 +/- 27.0 and
      302.5 +/- 20.1 nm, respectively. The U-46619-induced increase of [3H]-thymidine
      incorporation into DNA of p28 -30 AO0 cells was potentiatedby PDGF (1 ng ml-1)
      and FCS (1%) and was inhibited by cinnamophilin (10 microM) and SQ29548 (1
      microM)with estimated pKB values 5.4 +/- 1.2 and 6.3 +/- 0.9, respectively.6.
      Cell cycle analysis revealed that U-46619-increased cell cycle progression was
      primarily due to a rapidtransition from the DNA synthetic (S) to the G2/mitotic
      (M) phase. Moreover, U-46619 also increasedprotein synthesis and cell numbers in
      VSMC. All these effects of U-46619 were inhibited bycinnamophilin and SQ29548.7.
      U-46619 caused phosphoinositide breakdown and increased the intracellular Ca2+
      concentration inVSMC, effects which were blocked by cinnamophilin and SQ29548.8
      These data indicate there are two U-46619 binding sites in AlO VSMC. The high
      affinity site is correlated to U-46619-induced vasoconstriction while the low
      affinity site is correlated to U-46619-mediated VSMC proliferation. These data
      also reveal that U-46619 stimulates the cell cycle progression in VSMC primarily
      through a rapid transition from S to G2/M. Since cinnamophilin inhibits
      TPreceptor-mediated VSMC proliferation, it may thus hold promising potential for
      the prevention of atherosclerosis or vascular diseases.

PMID- 8528564
TI  - The effect of folate on the methotrexate/indomethacin interaction in a murine
      cancer cell line.
AB  - 1. The effect of folate on the interaction between methotrexate (a folate
      analogue) and indomethacin has been examined in murine NC carcinoma cells. 2.
      Conditioning of NC cells to a physiological (20 nM) folate concentration after
      culture in a high folate concentration increased the response to methotrexate.
      The sensitivity of these conditioned cells to methotrexate related inversely to
      the folate concentration. 3. At 20 nM and 2 microM folate, indomethacin 1
      micrograms ml-1 potentiated the cytotoxicity of methotrexate 4 and 8 ng ml-1
      (both P < 0.03). 4. When NC cells were incubated with [3H]-methotrexate at 20 nM
      and 2 microM folate, there was a trend for increased tritium accumulation with
      indomethacin 0.36 micrograms ml-1 (1 microM; P < 0.01). 5. We conclude that the
      folate concentration can affect the sensitivity of NC cells to methotrexate,
      although the degree of potentiation of cytotoxicity by indomethacin remains
      similar.

PMID- 8528565
TI  - Effects of nicorandil on the recovery of reflex potentials after spinal cord
      ischaemia in cats.
AB  - 1. The pathophysiological significance of ATP-sensitive K+ (KATP) channels in the
      central nervous system is not fully understood. In this study the effects of
      nicorandil (a hybrid vasodilator having a dual mechanism of action as a K+
      channel opener and a nitrate) on the recovery of the spinal cord reflex
      potentials after spinal cord ischaemia were examined and compared with those of
      pinacidil and nitroprusside in anaesthetized spinal cats. 2. Spinal cord
      ischaemia was produced by occlusion of the thoracic aorta and the bilateral
      internal mammary arteries for 10 min. Regional blood flow in the spinal cord was
      continuously measured with a laser-Doppler flow meter. The monosynaptic (MSR) and
      polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of the
      tibial nerve, were recorded from the lumbo-sacral ventral root. The recovery
      process of spinal reflex potentials was reproducible when the occlusion was
      repeated twice at an interval of 120 min. 3. Pretreatment with nicorandil (30-100
      micrograms kg-1) accelerated the recovery of PSR potentials after spinal cord
      ischaemia. Such an accelerating effect on the recovery of PSR potentials was also
      shared by pinacidil (100 micrograms kg-1), another K+ channel opener. In
      addition, the accelerating effect of nicorandil (100 micrograms kg-1) on the
      recovery of PSR potentials was abolished by co-administration of glibenclamide (3
      mg kg-1), a sulphonylurea KATP channel blocker. Nitroprusside (8 micrograms kg
      1min-1) retarded rather than improved the recovery of PSR potentials after spinal
      cord ischaemia. All of these drugs failed to improve the spinal cord blood flow
      during ischaemia and reperfusion. 4 These results suggest that nicorandil
      promotes the recovery of polysynaptic reflex potentials after spinal cord
      ischaemia by opening the KATP channels of neurones rather than by increasing
      local bloodflow. K+ channel openers may exert a salutary effect on the functional
      recovery of the ischaemic spinal cord.

PMID- 8528566
TI  - Phosphoramidon inhibition of the in vivo conversion of big endothelin-1 to
      endothelin-1 in the human forearm.
AB  - 1. The vasoconstrictor peptide, endothelin-1 (ET-1) and a biologically inactive C
      terminal fragment (CTF) are generated from an intermediate big ET-1 by a putative
      ET converting enzyme, sensitive to phosphoramidon. We have developed a procedure
      using selective solid-phase extraction and specific radioimmunoassays to measure
      the levels of immunoreactive (IR) big ET-1 and the products of conversion (ET-1
      and CTF) in human plasma. These techniques have been used to determine the levels
      of the three peptides in venous plasma following local infusions of ET-1 and big
      ET-1, both alone and together with phosphoramidon. 2. Infusion of ET-1 into the
      brachial artery (5 pmol min-1) significantly increased (P < 0.05) IR ET levels
      from a basal level of 2.3 pM to 55.2 pM in plasma from the infused arm after 60
      min of infusion. This corresponded with a marked decrease in forearm blood flow
      from a basal level of 2.6 ml dl-1 min-1 to 1.7 ml dl-1 min-1. The levels of IR
      big ET-1 and CTF were unchanged. Co-infusion of phosphoramidon (30 nmol min-1)
      with ET-1 had no significant effect on the plasma IR levels of ET, big ET-1, CTF,
      or blood flow. 3. Big ET-1 (50 pmol min-1) significantly increased (P < 0.05)
      venous concentrations of all three IR peptides after 60 min compared to basal
      (ET: from 2.2 to 7.7 pM, big ET-1; from 0 to 386.0 pM, CTF: from 0.2 to 37.0 pM).
      Forearm blood flow decreased significantly (P<0.05) from a basal level of 3.0 ml
      dl-1 min-1 to 1.6 ml dl-1 min-1.4. When phosphoramidon was co-infused with big ET
      1, both the rise in IR ET and associated vasoconstriction were abolished.
      However, IR CTF was still detected, suggesting that either some conversion by
      phosphoramidon-insensitive enzyme(s) was occurring, and/or that CTF was being
      protected from further degradation by phosphoramidon.5. These data show that in
      the human forearm the activity of a phosphoramidon-sensitive ET converting enzyme
      is at least in part responsible for the vasoconstrictor properties of exogenous
      big ET-1. Furthermore, because measurable levels of newly synthesized ET-1 are
      likely to be rapidly reduced in the blood/plasma through receptor binding, assay
      of IR big ET-1 and CTF may be a more sensitive measure of ET-1 generation in
      disease.

PMID- 8528567
TI  - Inhibition of angiogenesis, tumour growth and metastasis by the NO-releasing
      vasodilators, isosorbide mononitrate and dinitrate.
AB  - 1. The effect of the nitric oxide (NO)-producing nitrovasodilators isosorbide
      mononitrate (ISMN) and isosorbide dinitrate (ISDN) were assessed on (a) the in
      vivo model of angiogenesis of the chick chorioallantoic membrane (CAM) and (b) on
      the growth and metastatic properties of the Lewis Lung carcinoma (LLC) in mice.
      2. Isosorbide 5-mononitrate (ISMN) and isosorbide dinitrate (ISDN), inhibited
      angiogenesis in the CAM dose-dependently. ISMN was more potent in inhibiting this
      process. Both compounds were capable of completely reversing the angiogenic
      effect of alpha-thrombin. These effects of ISMN and ISDN on angiogenesis were
      comparable to those previously observed with sodium nitroprusside which generates
      NO non-enzymatically. 3. Mice, implanted intramuscularly with LLC, received daily
      i.p. injections of ISMN for 14 days resulting in a significant decrease in the
      size of the primary tumour and a reduction in the number and size of metastatic
      foci in the lungs. ISDN had a similar but less pronounced effect than that
      observed with ISMN. 4. Addition of ISMN or ISDN to cultures of bovine, rabbit and
      human endothelial cells and to cultures of LLC cells had no effect on their
      growth characteristics. 5. These results indicate that ISMN and ISDN inhibit
      angiogenesis and tumor growth and metastasis in an animal tumour model. The
      possibility should therefore be considered that these nitrovasodilators which are
      widely used therapeutically and have well characterized pharmacological profiles,
      may also possess antitumour properties in the clinic.

PMID- 8528568
TI  - Beta-adrenoceptor subtypes in young and old rat ventricular myocytes: a combined
      patch-clamp and binding study.
AB  - 1. We used electrophysiological and binding techniques to assess the presence of
      beta 1- and beta 2-adrenoceptors (beta 1AR and beta 2AR) in rat cardiac myocytes
      and to determine their ratio during aging. Experiments were performed in left
      ventricular myocytes enzymatically dissociated from the heart of 3-(young) or 22
      month-old (old) Wistar Kyoto rats. 2. In patch-clamp experiments, myocytes from
      old rats showed a prolonged action potential duration (at -20 mV: 41.7 +/- 3.6 vs
      26.2 +/- 3.1 ms; at -60 mV: 154.4 +/- 17.7 vs 87.1 +/- 6.9 ms, P < 0.05) and an
      augmented membrane capacitance (an index of cell size) (271.7 +/- 20.2 vs 164.3
      +/- 14.6 pF, P < 0.05) compared to young rats. beta 2AR stimulation, achieved by
      superfusing myocytes with the selective beta 2AR agonist, zinterol (10 microM) or
      with (-)-isoprenaline (1 microM) in the presence of the selective beta 1AR
      antagonist, CGP 20712A (0.1 microM), significantly increased L-type calcium
      current (ICa,L) in rat ventricular myocytes. The percentage increase was similar
      in both young and old rats, either with zinterol (26.9 +/- 3.6% and 24.2 +/-
      2.8%, respectively) or isoprenaline plus CGP 20712A (30.4 +/- 3.7% and 22.4 +/-
      4.1%, respectively). Isoprenaline alone (beta 1AR and beta 2AR stimulation)
      caused a much smaller increase in ICa,L in old rats (58.4 +/- 12.1%) than in
      younger ones (95.3 +/- 8.1%) (P = 0.067). 3 The number of ,BAR mg-' protein,
      measured with saturation binding assays of the non selective ,betaAR antagonist
      [3H]-CGP 12177 was 1989.4+/-189.5 for 3- and of 1580.7 +/-161.5 for 22-month-old
      rats.Competition for [3H]-CGP 12177 binding by CGP 20712A gave biphasic curves
      which demonstrated two classes of binding sites. Densities (as percentages of
      total PAR density), and affinities for the two binding sites were: 80.4 +/- 2.2%
      (Ki = 6.6 +/- 1.3 nM) betaAR and 19.6 +/- 2.2% (Ki = 6.9 +/- 2.2 microM) beta2AR
      in young rats and 66.1 +/- 1.2% (Ki=8.3+/- 1.1 nM) beta1 AR and 33.9+/- 1.2%
      (Ki=5.2+/-0.6 PM) P2AR in old rats. Thebeta1AR/beta2AR ratio was significantly
      (P<0.01) reduced in old rats with respect to the younger ones.4 By combining
      electrophysiological and binding measurements, we calculated beta1AR and
      beta2ARdensities as number of receptors per microM2 of cell surface. In old rats,
      beta1 density was significantly decreased compared to young rats (8.4+/-2.0 vs
      15.4+/-3.7 receptors microM-2, P<0.05), while beta2AR density remained unchanged
      at both 3 and 22 months (3.8 +/- 0.7 and 4.2+/-1.1 receptors microM-2,
      respectively).5 Our results demonstrate that both beta1AR and beta2AR are
      functionally present in rat ventricular myocytes of young and old rats. The
      decreased responsiveness to betaAR stimulation during aging appears to be
      associated with a selective reduction in the density of beta1AR.

PMID- 8528569
TI  - Involvement of superoxide and xanthine oxidase in neutrophil-independent rat
      gastric damage induced by NO donors.
AB  - 1. Nitric oxide (NO) and the superoxide anion can interact to form the cytotoxic
      moiety, peroxynitrite. The involvement and potential source of superoxide in the
      gastric mucosal damage induced by local infusion of NO donors, has now been
      investigated in the pentobarbitone-anaesthetized rat. 2. Local intra-arterial
      infusion of the NO donor, sodium nitroprusside (40 micrograms kg-1 min-1) for 10
      min induced macroscopically apparent gastric mucosal injury. 3. This mucosal
      damage was dose-dependently reduced by prior administration of a systemically
      acting form of superoxide dismutase conjugated with polyethylene glycol (500-2000
      iu kg-1, i.v.). 4. Likewise, the mucosal damage induced by nitroprusside was dose
      dependently reduced by prior administration of the xanthine oxidase inhibitor,
      allopurinol (20-100 mg kg-1, i.p. or 100 mg kg-1, p.o.). 5. Pretreatment with
      allopurinol (100 mg kg-1, i.p.) also reduced the mucosal injury induced by local
      intra-arterial infusion of the nitrosothiol, S-nitroso-N-acetyl-penicillamine (40
      micrograms kg-1 min-1), but not that induced by local infusion of endothelin-1 (5
      pmol kg-1 min-1), indicating specificity of action. 6. Prior administration (4h)
      of rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p.), which reduced
      circulating neutrophils by 90%, did not significantly protect against mucosal
      injury induced by nitroprusside. 7. Intravenous administration of the platelet
      activating factor receptor antagonists, WEB 2086 (1 mg kg-1) or BN 52021 (10 mg
      kg-1), or the thromboxane synthase inhibitor, OKY 15181 (25 mg kg-1), did not
      modify mucosal damage induced by nitroprusside, showing lack of involvement of
      these neutrophil-derived mediators. 8. These findings indicate the involvement of
      superoxide in the injurious actions of the NO donors, implicating a cytotoxic
      role of peroxynitrite. Xanthine oxidase, but not neutrophils, appears to be a
      source of the superoxide.

PMID- 8528570
TI  - Differential modulation of voltage-activated conductances by intracellular and
      extracellular cyclic nucleotides in leech salivary glands.
AB  - 1. Two-electrode voltage clamp was used to study the effects of adenosine 3':5'
      cyclic monophosphate (cyclic AMP) and guanosine 3':5'-cyclic monophosphate
      (cyclic GMP) on voltage-dependent ion channels in salivary gland cells of the
      leech, Haementeria ghilianii. 2. Intracellular cyclic AMP specifically blocked
      delayed rectifier K+ channels. This was shown by use of 3-isobutyl-1
      methylxanthine (IBMX, a phosphodiesterase inhibitor), forskolin (an activator of
      adenylyl cyclase) and intracellular injection of cyclic AMP and its dibutyryl and
      8-bromo analogues. Cyclic AMP appeared to be the second messenger for the
      putative neuroglandular transmitter, 5-hydroxytryptamine. 3. Intracellular
      injection of cyclic GMP specifically potentiated high-voltage-activated (HVA)
      Ca2+ current and the effect was mimicked by zaprinast, an inhibitor of cyclic GMP
      dependent phosphodiesterase. 4. Extracellularly, cyclic GMP and cyclic AMP
      specifically decreased the amplitude and increased the rate of inactivation of
      HVA Ca2+ current. These effects of the cyclic nucleotides are identical to those
      known for extracellular ATP, which activates a presumed purinoceptor. The
      pyrimidine nucleotide, UTP, was almost equipotent to ATP (threshold dose < 10(-6)
      M), indicative of a vertebrate-type nucleotide receptor. However, suramin (5 x
      10(-5) M), a non-specific P2-receptor antagonist, failed to block the effects of
      5 x 10(-6) M ATP (higher suramin doses could not be reliably tested because of
      the depolarization and increase in membrane conductance produced by the drug). 5.
      Activation of the putative purinoceptor by ATP did not affect inward rectifier
      Na+/K+ current which is known to be potentiated by intracellular cyclic AMP and
      reduced by intracellular cyclic GMP. 6. The preparation may provide a useful
      model for study of nucleotide actions, and interactions, in channel modulation.
      It has technical advantages such as large cells (1200 microns in diameter) which
      lack intercellular coupling and may be individually dissected for biochemical
      studies.

PMID- 8528571
TI  - Pharmacology of postsynaptic metabotropic glutamate receptors in rat hippocampal
      CA1 pyramidal neurones.
AB  - 1. Activation of metabotropic glutamate receptors (mGluRs) in hippocampal CA1
      pyramidal neurones leads to a depolarization, an increase in input resistance and
      a reduction in spike frequency adaptation (or accommodation). At least eight
      subtypes of mGluR have been identified which have been divided into three groups
      based on their biochemical, structural and pharmacological properties. It is
      unclear to which group the mGluRs which mediate these excitatory effects in
      hippocampal CA1 pyramidal neurones belong. We have attempted to address this
      question by using intracellular recording to test the effects of a range of mGluR
      agonists and antagonists, that exhibit different profiles of subtype specificity,
      on the excitability of CA1 pyramidal neurones in rat hippocampal slices. 2. (2S,
      1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1) caused a reduction in spike
      frequency adaptation and a depolarization (1-10 mV) associated with an increase
      in input resistance (10-30%) at concentrations (> or = 50 microM) that have been
      shown to activate mGluRs in groups I, II and III. Similar effects were observed
      with concentrations (50-100 microM) of (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid ((1S,3R)-ACPD) and (1S,3S)-ACPD that exhibit little or no
      activity at group III mGluRs but which activate groups I and II mGluRs. 3.
      Inhibition of the release of endogenous neurotransmitters through activation of
      GABAB receptors, by use of 200 microM (+/-)-baclofen, did not alter the effects
      of (1S,3R)-ACPD (50-100 microM), (1S,3S)-ACPD (100 microM) or L-CCG1 (100
      microM). This suggests that mGluR agonists directly activate CA1 pyramidal
      neurones. 4. Like these broad spectrum mGluR agonists, the racemic mixture ((SR)
      ) or resolved (S)-isomer of the selective group I mGluR agonist 3,5
      dihydroxyphenylglycine ((SR)-DHPG (50-100 microM) or (S)-DHPG (20-50 microM))
      caused a reduction in spike frequency adaptation concomitant with postsynaptic
      depolarization and an increase in input resistance. In contrast, 2S,1'R,2'R,3'R-2
      (2',3'-dicarboxycyclopropyl)glycine (DCG-IV; 100 microM) and (S)-2-amino-4
      phosphonobutanoic acid (L-AP4; 100-500 microM), which selectively activate group
      II mGluRs and group III mGluRs, respectively, had no effect on the passive
      membrane properties or spike frequency adaptation of CA1 pyramidal neurones. 5.
      The mGluR antagonists (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG; 1000
      microM) and (S)-4-carboxyphenylglycine ((S)-4CPG; 1000 microM), which block
      groups I and II mGluRs and group I mGluRs, respectively, had no effect on
      membrane potential, input resistance or spike frequency adaptation per se. Both
      of these antagonists inhibited the postsynaptic effects of (1S,3R)-ACPD (50-100
      microM), (1S,3S)-ACPD (30-100 microM) and L-CCG1 (50-100 microM). (+)-MCPG also
      reversed the effects of (SR)-DHPG(75 gM). (The effect of (S)-4CPG was not
      tested.) Their action was selective in that both antagonists did not reverse the
      reduction in spike frequency adaptation induced by carbachol (1 microM) or
      noradrenaline(10 microM) whereas atropine (10 microM) and propranolol (100
      microM) did.6 From these data it is concluded that the mGluRs in CAl pyramidal
      neurones responsible for these excitatory effects are similar to the mGluRs
      expressed by non-neuronal cells transfected with cDNA encoding group I mGluRs.

PMID- 8528572
TI  - Enhancement by benzodiazepines of the inhibitory effect of adenosine on skeletal
      neuromuscular transmission.
AB  - 1. Interactions of benzodiazepines with adenosine on the neuromuscular
      transmission were studied in mouse diaphragm preparations. 2. In tubocurarine
      (0.6-0.8 microM)-partially paralyzed preparations, diazepam (35 microM) and Ro 5
      4864 (3-30 microM), a peripheral type benzodiazepine receptor agonist,
      potentiated the inhibitory effect of adenosine on indirect twitch responses. 3.
      The central type receptor agonist, clonazepam did not affect the inhibitory
      effect of adenosine. 4. The peripheral benzodiazepine receptor antagonist,
      PK11195 (1-10 microM) attenuated the adenosine inhibition and antagonized the
      potentiation by Ro 5-4864. 5. Ro 5-4864 failed to enhance further the inhibitory
      effect of adenosine in the presence of dipyridamole, an adenosine uptake
      inhibitor that also potentiated adenosine inhibition. 6. Neither Ro 5-4864 nor PK
      11195 affected the inhibition produced by a stable adenosine analogue, 2
      chloroadenosine, which is not a substrate for the adenosine uptake system. 7. Ro
      5-4864 did not affect endplate potentials (e.p.ps) in the absence of adenosine,
      but reduced the amplitude of e.p.ps in the presence of adenosine without
      affecting miniature e.p.ps. 8. It is suggested that benzodiazepines potentiate
      the adenosine-effected presynaptic inhibition of neuromuscular transmission by an
      inhibition of adenosine uptake through activation of peripheral type
      benzodiazepine receptors.

PMID- 8528573
TI  - Pharmacological modulation of adrenal medullary GABAA receptor: consistent with
      its subunit composition.
AB  - 1. Muscimol, the specific GABAA receptor agonist, increased the secretion of
      catecholamines by chromaffin cells with an EC50 of 2.9 +/- 0.4 microM. 2. GABAA
      receptors of these cells were modulated by the same drugs which modulate GABAA
      receptors in brain tissue. 3. Benzodiazepines enhanced muscimol-evoked
      catecholamine secretion by between 20 and 80%. This effect seems to be mediated
      by binding to a central type of benzodiazepine receptor because it was completely
      blocked by the specific antagonist, Ro 15 1788. This antagonist was able to
      displace [3H]-flunitrazepam binding with an EC50 of 0.26 +/- 0.05 nM. 4. beta
      Carbolines weakly inhibited muscimol-induced catecholamine secretion and were
      able to displace [3H]-flunitrazepam binding with an EC50 between 0.2 and 0.9 nM,
      depending on the beta-carboline used. 5. Pregnanolone and related neuroactive
      steroids enhanced muscimol-evoked catecholamine secretion by up to 87%, in a dose
      dependent fashion. In contrast pregnenolone weakly inhibited muscimol-evoked
      catecholamine secretion. 6. Zn2+ did not affect GABAA receptor-induced
      catecholamine secretion. 7. These pharmacological results are absolutely
      concordant with the theoretical properties given by the GABAA receptor subunit
      composition of bovine adrenal medulla -alpha 1, alpha 4, beta 1-3, gamma 2
      previously characterized by Western blot analysis.

PMID- 8528574
TI  - Modulation of calcium currents by G-proteins and adenosine receptors in myenteric
      neurones cultured from adult guinea-pig small intestine.
AB  - 1. Whole-cell patch clamp methods were used to analyse voltage-dependent calcium
      currents in cultured myenteric neurones enzymatically isolated from adult guinea
      pig small intestine. 2. Activation of G-proteins by intracellular administration
      of GTP-gamma-S (100-200 microM in pipette) decreased the amplitude of high
      voltage activated Ca2+ current (ICa) by more than 50%. Residual ICa was activated
      more slowly and was non-inactivating during 500 ms test pulses when GTP-gamma-S
      was included in the pipette solution. 3. Inclusion of 500 microM GDP-beta-S in
      the patch pipettes increased the amplitude of ICa by over 30% without altering
      the voltage-dependency. 4. Extracellular application of 2-chloroadenosine
      suppressed ICa dose-dependently by reducing both transient and sustained
      components of the current. 5. Pretreatment of the neurones with cholera toxin or
      forskolin did not alter the actions of GTP-gamma-S or GDP-beta-S or 2
      chloroadenosine. 6. The results suggest that high threshold calcium channels in
      myenteric neurones are influenced by G-proteins and that the inhibitory action of
      2-chloroadenosine on ICa involves G-protein coupling of the adenosine receptors
      to the Ca2+ channel.

PMID- 8528575
TI  - Modulation of calcium channel currents by arachidonic acid in single smooth
      muscle cells from vas deferens of the guinea-pig.
AB  - 1. Effects of arachidonic acid (AA) on voltage-dependent Ca channel currents were
      investigated by whole-cell-clamp methods in single smooth muscle cells freshly
      isolated from vas deferens of the guinea-pig. 2. Ca channel current was decreased
      by application of 1-30 microM AA in a concentration-dependent manner. When Ca2+
      or Ba2+ was the charge carrier, Ca channel current (ICa or IBa) was reduced by AA
      to a similar extent (IC50 = 10 and 6 microM, respectively). Addition of 15 mM
      BAPTA to the pipette solution did not affect the reduction of IBa by 10 microM
      AA. 3. The effect of AA on IBa was not prevented by internal application of 1 mM
      nordihydroguaiaretic acid (NDGA) and 1 mM indomethacin (Indo). When the pipette
      solution contained 0.1 mM guanosine-5'-triphosphate (GTP), IBa was decreased
      slightly but significantly by application of 30 microM prostaglandin F2 alpha
      (PGF2 alpha) but not by PGE2. This effect of PGF2 alpha was irreversible or not
      observed when the pipette solution contained 0.3 mM guanosine-5'-(3
      thiotriphosphate) (GTP gamma S) or both GTP or guanosine-5'-O-(2-thiodiphosphate)
      (GDP beta S), respectively. 4. External application of 100 units ml-1 superoxide
      dismutase slightly but significantly attenuated the inhibition of IBa by 1-30
      microM AA. Intracellular application of 1 mM GDP beta S or 0.3 mM GTP gamma S did
      not significantly change the effect of AA. Intracellular application of 0.1 mM 1
      (5-isoquinolinesulphonyl)-2-methylepiperazine (H-7) also did not change the
      effect of AA. 5. These results indicate that the decrease in Ca channel currents
      in vas deferens smooth muscle cells is mainly due to AA itself, as opposed to its
      metabolites. The effect of AA may be due to AA itself, as opposed to its
      metabolites. The effect of AA may be due to its direct action on Ca channels or
      membrane phospholipids, but may not be mediated by activation of GTP binding
      proteins or protein kinase C. The inhibition of Ca channel current by AA may be
      partly induced by superoxide radicals derived from AA oxidation. PGF2A also
      reduces Ca channel currents but probably by a separate mechanism via activation
      of a GTP binding protein.

PMID- 8528576
TI  - Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on
      mitochondrial respiration in ischaemic dog hearts.
AB  - 1. Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors, pravastatin and simvastatin, on the myocardial level of coenzyme Q10,
      and on mitochondrial respiration were examined in dogs. 2. Either vehicle
      (control), pravastatin (4 mg kg-1 day-1), or simvastatin (2 mg kg-1 day-1) was
      administered orally for 3 weeks. First, the myocardial tissue level of coenzyme
      Q10 was determined in the 3 groups. Second, ischaemia was induced by ligating the
      left anterior descending coronary artery (LAD) in anaesthetized open chest dogs,
      pretreated with the inhibitors. After 30 min of ischaemia, nonischaemic and
      ischaemic myocardium were removed from the left circumflex and LAD regions,
      respectively, and immediately used for isolation of mitochondria. The
      mitochondrial respiration was determined by polarography, with glutamate and
      succinate used as substrates. 3. Simvastatin significantly decreased the
      myocardial level of coenzyme Q10, but pravastatin did not. 4. Ischaemia decreased
      the mitochondrial respiratory control index (RCI) in both groups. Significant
      differences in RCI between nonischaemic and ischaemic myocardium were observed in
      the control and simvastatin-treated groups. 5. Only in the simvastatin-treated
      group did ischaemia significantly decrease the ADP/O ratio, determined with
      succinate. 6. The present results indicate that simvastatin but not pravastatin
      may cause worsening of the myocardial mitochondrial respiration during ischaemia,
      probably because of reduction of the myocardial coenzyme Q10 level.

PMID- 8528577
TI  - Characterization of the effect of SR48692 on inositol monophosphate, cyclic GMP
      and cyclic AMP responses linked to neurotensin receptor activation in neuronal
      and non-neuronal cells.
AB  - 1. Neurotensin stimulated inositol monophosphate (IP1) formation in both human
      colonic carcinoma HT29 cells and in mouse neuroblastoma N1E115 cells with EC50
      values of 3.5 +/- 0.5 nM (n = 4) and 0.46 +/- 0.02 nM (n = 3), respectively.
      Neurotensin also stimulated cyclic GMP production with an EC50 of 0.47 +/- 1.2 nM
      and inhibited cyclic AMP accumulation induced by forskolin (0.5 microM) with an
      IC50 of 1.33 +/- 1.5 nM (n = 3) on the N1E115 cell line. 2. The competitive
      antagonism by the non-peptide neurotensin receptor antagonist, SR48692 of
      neurotensin-induced IP1 formation revealed pA2 values of 8.7 +/- 0.2 (n = 3) for
      HT29 and 10.1 +/- 0.2 (n = 3) for N1E115 cells. SR48692 also antagonized the
      cyclic GMP and cyclic AMP responses induced by neurotensin in the N1E115 cell
      line with pA2 values of 10.7 +/- 0.7 (n = 3) and 9.8 +/- 0.3 (n = 3),
      respectively. 3. In CHO cells transfected with the rat neurotensin receptor,
      neurotensin stimulated IP1 and cyclic AMP formation with EC50 values of 3.0 +/-
      0.5 nM (n = 3) and 72.2 +/- 20.7 nM (n = 3), respectively. Both effects were
      antagonized by SR48692, giving pA2 values of 8.4 +/- 0.1 (n = 3) for IP1 and 7.2
      +/- 0.4 (n = 3) for cyclic AMP responses. 4. Radioligand binding experiments,
      performed with [125I]-neurotensin (0.2 nM), yielded IC50 values of 15.3 nM (n =
      2) and 20.4 nM (n = 2) for SR48692 versus neurotensin receptor binding sites
      labelled in HT29 and N1E115 cells, respectively. 5 In conclusion, SR48692 appears
      to be a potent, species-independent antagonist of the signal transduction events
      triggered by neurotensin receptor activation in both neuronal and non-neuronal
      cell systems.

PMID- 8528578
TI  - Discrimination by the NO-trapping agent, carboxy-PTIO, between NO and the
      nitrergic transmitter but not between NO and EDRF.
AB  - 1. The effects of carboxy-PTIO, a scavenger of free radical nitric oxide (NO),
      were studied on endothelium-dependent relaxations of rat aorta and nitrergic
      nerve stimulation-induced relaxations of anococcygeus muscle and gastric fundus
      strips to test the hypothesis that endothelium-derived relaxing factor (EDRF) and
      the transmitter released by nitrergic nerves is free radical NO. 2. Carboxy-PTIO
      (10-300 microM) produced concentration-dependent reductions of relaxations
      elicited by exogenous NO, and relaxations mediated by EDRF released by
      acetylcholine and ATP in rings of rat aorta. The inhibitory effect of carboxy
      PTIO was removed by washing the tissues. 3. In the rat anococcygeus muscle,
      carboxy-PTIO (10-300 microM) produced concentration-dependent reductions of
      relaxations to exogenous NO; however, in concentrations up to 2000 microM it did
      not reduce relaxations elicited by nitrergic nerve stimulation (1-2 Hz), in fact,
      concentrations of 300 microM or more slightly enhanced them. 4. In rat gastric
      fundus strips, carboxy-PTIO (100 and 300 microM) reduced relaxations to exogenous
      NO, but relaxations elicited by stimulation of the nitrergic component of non
      adrenergic, non-cholinergic nerves were not affected. 5. These results suggest
      that EDRF is free radical NO and may be designated EDNO, but the transmitter
      released from nitrergic nerves does not appear to be identical to EDNO and may
      not be free radical NO.

PMID- 8528579
TI  - Restoration of blood pressure by choline treatment in rats made hypotensive by
      haemorrhage.
AB  - 1. Intracerebroventricular (i.c.v.) injection of choline (25-150 micrograms)
      increased blood pressure in rats made acutely hypotensive by haemorrhage.
      Intraperitoneal administration of choline (60 mg kg-1) also increased blood
      pressure, but to a lesser extent. Following i.c.v. injection of 25 micrograms or
      50 micrograms of choline, heart rate did not change, while 100 micrograms or 150
      micrograms i.c.v. choline produced a slight and short lasting bradycardia.
      Choline (150 micrograms) failed to alter the circulating residual volume of blood
      in haemorrhaged rats. 2. The pressor response to i.c.v. choline (50 micrograms)
      in haemorrhaged rats was abolished by pretreatment with mecamylamine (50
      micrograms, i.c.v.) but not atropine (10 micrograms, i.c.v.). The pressor
      response to choline was blocked by pretreatment with hemicholinium-3 (20
      micrograms, i.c.v.). 3. The pressor response to i.c.v. choline (150 micrograms)
      was associated with a several fold increase in plasma levels of vasopressin and
      adrenaline but not of noradrenaline and plasma renin. 4. The pressor response to
      i.c.v. choline (150 micrograms) was not altered by bilateral adrenalectomy, but
      was attenuated by systemic administration of either phentolamine (10 mg kg-1) or
      the vasopressin antagonist [beta-mercapto-beta,beta-cyclopenta
      methylenepropionyl1, O-Me-Tyr2,Arg8]-vasopressin (10 micrograms kg-1). 5. It is
      concluded that the precursor of acetylcholine, choline, can increase and restore
      blood pressure in acutely haemorrhaged rats by increasing central cholinergic
      neurotransmission. Nicotinic receptor activation and an increase in plasma
      vasopressin and adrenaline level appear to be involved in this effect of choline.

PMID- 8528580
TI  - Enhanced sympathetic neurotransmission in the tail artery of 1,3-dipropyl-8
      sulphophenylxanthine (DPSPX)-treated rats.
AB  - 1. Sympathetic neurotransmission and noradrenaline content of the tail artery of
      Wistar rats treated for 7 days with the adenosine antagonist, 1,3-dipropyl-8
      sulphophenylxanthine (DPSPX), were examined. 2. Systolic blood pressure of the
      DPSPX-treated rats (164.0 +/- 2.9 mmHg; n = 6) was significantly greater than
      saline-treated controls (140.0 +/- 2.8 mmHg; n = 5) after 7 days treatment. 3.
      The pressor responses of the arterial rings to transmural nerve stimulation (65
      V, 0.1 ms, 4-64 Hz, for 1 s) were markedly enhanced in the DPSPX-treated compared
      with the saline-treated animals. Both noradrenergic and purinergic components of
      perivascular sympathetic neurotransmission were enhanced during DPSPX-induced
      hypertension. 4. Vasoconstrictor responses to exogenous noradrenaline (0.1-300
      microM) and adenosine 5'-triphosphate (0.01-3 mM) were unaffected after DPSPX
      treatment, indicating prejunctional alteration of sympathetic cotransmission
      during DPSPX-induced hypertension. 5. Acute exposure to DPSPX (10 microM) did not
      modify vasoconstrictor responses to transmural nerve stimulation, thus supporting
      the claim that the enhancement of sympathetic neurotransmission only results from
      long-term DPSPX treatment. 6. The noradrenaline content of the tail arteries of
      DPSPX-treated (4.498 +/- 0.26 ng cm-1; n = 4) was significantly greater than
      saline-treated (3.440 +/- 0.30 ng cm-1; n = 5) animals. 7. These findings show
      that chronic inhibition of the actions of endogenous adenosine by DPSPX results
      in an elevation of systolic blood pressure accompanied by enhanced sympathetic
      cotransmission and enhanced noradrenaline content of the rat tail artery.

PMID- 8528581
TI  - Differential effects of acute and chronic fluoxetine administration on the
      spontaneous activity of dopaminergic neurones in the ventral tegmental area.
AB  - 1. Electrophysiological techniques were used to study the effects of fluoxetine
      and citalopram on the basal activity of dopaminergic neurones in the ventral
      tegmental area (VTA) and substantia nigra, pars compacta (SNc) of rats. 2. Acute
      i.v. injection of fluoxetine (20-1280 micrograms kg-1) caused a dose-dependent
      inhibition of the firing rate of VTA dopaminergic neurones, but did not affect
      the activity of dopaminergic cells in the SNc. Citalopram (20-1280 micrograms kg
      1, i.v.) inhibited the firing rate of dopaminergic neurones in the VTA, but its
      effect (maximal inhibition: 14 +/- 7%) was less pronounced than that of
      fluoxetine (maximal inhibition: 34 +/- 7%). 3. Pretreatment with mesulergine (80
      micrograms kg-1, i.v.), a 5-hydroxytryptamine2C/2B (5-HT2C/2B) receptor
      antagonist, blocked the inhibitory effect of fluoxetine on VTA dopaminergic
      cells. Selective lesions of 5-hydroxytryptaminergic neurones by the neurotoxin,
      5,7-dihydroxytryptamine (5,7-DHT), abolished the fluoxetine-induced reduction of
      VTA dopaminergic activity. 4. In a series of experiments, fluoxetine (10 mg kg-1,
      i.p.) was administered once daily for 21 consecutive days. Acute i.v.
      administration of fluoxetine (20-1280 micrograms kg-1, 72 h after the last i.p.
      injection) did not cause any change in the basal firing rate of VTA dopaminergic
      neurones in treated rats, whereas it induced the typical inhibitory effect in
      control animals. A group of rats chronically treated with fluoxetine, received
      i.v. m-chlorophenylpiperazine (mCPP; 10-320 micrograms kg-1), a 5-HT2C/2B
      receptor agonist. This drug significantly inhibited VTA dopaminergic function in
      control rats, but did not modify the basal activity of dopaminergic cells in
      animals given chronic fluoxetine. 5 It is concluded that fluoxetine inhibits
      dopaminergic function in the VTA by enhancing the synaptic levels of 5-HT, which
      possibly acts through the 5-HT2C/2B receptor subtype. Repeated treatment with
      fluoxetine induces tolerance to its inhibitory effect on dopaminergic activity,
      possibly as a consequence of down-regulation of 5-HT2C/2B receptors. The effects
      of fluoxetine on VTA dopaminergic cell activity might be relevant for its
      therapeutic actions and may explain the origin of the reported cases of
      akathisia.

PMID- 8528582
TI  - Vasoconstrictor responses to the P2x-purinoceptor agonist beta, gamma-methylene-L
      ATP in human cutaneous and renal blood vessels.
AB  - 1. Strips of human saphenous veins and of human renal arteries and veins were
      superfused with Krebs-Henseleit solution at 37 degrees C. Constrictor responses
      were elicited by exogenous noradrenaline and the P2x-purinoceptor-selective
      agonist, beta, gamma-methylene-L-ATP. 2. In human saphenous veins, beta, gamma
      methylene-L-ATP (0.3-30 microM; EC50 2.2 microM) induced marked constrictor
      responses. The maximal response to beta, gamma-methylene-L-ATP was similar to the
      maximal response to noradrenaline. The P2-purinoceptor antagonist suramin (30
      microM) shifted the concentration-response curve of beta, gamma-methylene-L-ATP
      to the right (apparent pKB value 4.8); suramin (100 microM) markedly inhibited
      the responses to beta, gamma-methylene-L-ATP. The preferential P2x-purinoceptor
      antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 3
      microM) slightly reduced the response to beta, gamma-methylene-L-ATP. At a ten
      times higher concentration (30 microM), PPADS almost abolished the responses to
      beta, gamma-methylene-L-ATP. PPADS (30 microM), in contrast, caused no
      significant change in the concentration-response curve of noradrenaline. 3. In
      extrarenal and intrarenal arteries, EC50 values and maximal responses to
      noradrenaline were similar when compared with responses to noradrenaline in
      saphenous veins. Noradrenaline also constricted extrarenal veins. However, in
      contrast to the results obtained on saphenous veins, beta, gamma-methylene-L-ATP
      caused almost no constrictor responses in extrarenal veins and arteries and only
      moderate responses in intrarenal arteries. 4. The results demonstrate marked
      differences in responsiveness of human blood vessels to the selective P2x
      purinoceptor agonist, beta, gamma-methylene-L-ATP, suggesting tissue differences
      in the occurrence or operation of P2x-purinoceptors in human vascular tissues.
      Moreover, the results indicate that PPADS blocks P2x-purinoceptors in human
      isolated blood vessels as previously demonstrated in animal blood vessels.

PMID- 8528583
TI  - Antinociceptive activity of the tachykinin NK1 receptor antagonist, CP-99,994, in
      conscious gerbils.
AB  - 1. The ability of CP-99,994, and its less active enantiomer, CP-100,263, to
      inhibit spontaneous behaviours and hyperalgesia induced by central infusion of
      the NK1 receptor agonist, GR73632 or intraplantar injection of formalin was
      investigated in rats and gerbils. 2. GR73632 (3 pmol, i.c.v.)-induced foot
      tapping in gerbils was dose-dependently inhibited by CP-99,994 (0.1-1 mg kg-1,
      s.c.), but not by CP-100,263 (10 mg kg-1, s.c.) using pretreatment times up to 60
      min. The centrally active dose-range for CP-99,994 was increased to 1-10 mg kg-1
      s.c. with a higher challenge dose of GR73632 (30 pmol, i.c.v.). 3. In gerbils,
      intrathecal (i.t.) injection of GR73632 (30 pmol) elicited behaviours (licking,
      foot tapping or flinching and face washing) which closely resembled, but which
      was less specifically localized than, behaviours seen in animals injected with
      formalin (0.1-5%) into one hindpaw. 4. In rats, CP-100,263, but not CP-99,994 (up
      to 30 mg kg-1), inhibited the early phase response to intraplantar injection of
      5% formalin (ID50 = 13.9 mg kg-1). The late phase was inhibited by both compounds
      (ID50 values 36.3 and 20.9 mg kg-1, respectively). In gerbils, there was marginal
      evidence for enantioselective inhibition of the early phase induced by formalin
      (2%). The ID50 values were 6.2 mg kg-1 for CP-99,994 and 13.4 mg kg-1 for CP
      100,263. 5. Intrathecal injection of GR73632 (30 pmol) caused thermal
      hyperalgesia in igerbils which was inhibited enantioselectively by s.c.
      administration of CP-99,994 (ID50= 2.46 mg kg-1), but not by CP-100,263 (30 mg kg
      1).6. In gerbils, intraplantar injection of formalin (0.1%) caused thermal
      hyperalgesia which was inhibited by CP-99,994 (ID50= 1.1 mg kg-1, s.c.). There
      was a nonsignificant trend for an anti-algesic effect of CP-100,236 (estimated
      ID50 = 8.2 mg kg-1, s.c.).7 These findings support the proposal that NK1 receptor
      antagonists may be useful in the clinical management of pain and reinforce the
      need to dissociate specific and nonspecific antinociceptive effects of available
      compounds.

PMID- 8528584
TI  - Loss of telomeric sites in the chromosomes of Mus musculus domesticus (Rodentia:
      Muridae) during Robertsonian rearrangements.
AB  - Mouse chromosomes possessing multiple Robertsonian rearrangements (Rb
      chromosomes) have been examined using fluorescence in situ hybridization with the
      telomeric consensus sequence (TTAGGG)n. No hybridization signals were detected at
      the primary constriction of Rb chromosomes. This observation leads us to conclude
      that the formation of Rb chromosomes in the mouse is invariably associated with
      the loss of telomeric regions. More significantly, a further alteration in
      regions flanking the primary constrictions was observed after hybridizing with a
      minor satellite DNA probe to Rb chromosomes. It seems likely that the breakpoints
      required for a Robertsonian process do not include telomeric sites exclusively
      but extend to the adjacent pericentromeric regions of the original acrocentric
      chromosomes. In contrast to previous reports, these observations demonstrate the
      elimination of substantial amounts of chromosomal DNA during the formation of
      mouse Rb chromosomes.

PMID- 8528585
TI  - Confirmation of the copy number of chromosome 1 in interphase nuclei from
      paraffin sections of breast tumours by fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) was used to establish the copy number
      of chromosome 1 in a set of nine breast tumours in which the chromosome had
      previously been shown to have undergone a variety of rearrangements by loss of
      heterozygosity studies. In each case, FISH with satellite III DNA from chromosome
      1q12 confirmed the results obtained by Southern hybridization. Importantly, in
      all five cases with rearrangements thought not to involve the centromeric region,
      FISH showed that the events had not disrupted the gross chromosome structure.
      This study highlights the potential of using the two techniques together to
      obtain a clearer picture of both large- and small-scale alterations to
      chromosomes in solid tumours.

PMID- 8528587
TI  - Brdu replication bands in the anguilliform fish Echelus myrus.
AB  - High-resolution replication banding patterns have been obtained in prometaphase
      and metaphase chromosomes of the anguilliform fish species Echelus myrus by
      treating kidney cell cultures with 5-bromodeoxyuridine during the mid-late
      synthesis phase. The results show the superiority of the in vitro technique in
      obtaining a higher number of bands which permit an accurate identification of all
      chromosome pairs. Different replication patterns were compared with C-bands and
      silver-stained nucleolus organizer regions, providing information on the
      replication order of different chromatin regions.

PMID- 8528586
TI  - Stable chromosome fission associated with rDNA mobility.
AB  - A spontaneous chromosome fission in the plant Hypochoeris radicata has been
      characterized by Feulgen staining, in situ hybridization of the rDNA probe pTA71
      and silver staining for active nucleolus organizing regions. The parental
      acrocentric chromosome has no detectable ribosomal genes at the centromere, but
      both fission derivatives possess active NORs at their centric ends. In fission
      heterozygotes, pachytene configurations studied by synaptonemal complex spreading
      show that the ribosomal cistrons form short arms on each telocentric which pair
      together to form a triradial. The paired short arms are associated with the
      single nucleolus at pachytene. It is proposed that the origin and stabilization
      of the fission rearrangement involved transposition of rDNA from the nucleolus
      organizing region of chromosome 3 into the centromeric region of chromosome 1.

PMID- 8528588
TI  - Mitotic and meiotic detection of radiation-induced translocations in mouse stem
      cell spermatogonia using fluorescence in situ hybridization.
AB  - The efficiency of two methods of detection of translocations induced in mouse
      stem cell spermatogonia by X-ray doses of 2, 5 and 7 Gy was compared: classical
      multivalent analysis at diakinesis-metaphase I of meiosis and observation via
      fluorescence in situ hybridization analysis of mitotic or meiotic stages.
      Specific DNA libraries for chromosomes 1, 11 and 13 were used. The results
      obtained indicate that (a) chromosomes 1, 11 and 13 are more involved in
      multivalent formation than expected on the basis of DNA content and (b) if the
      mitotic FISH analysis data are corrected for the observed over-representation,
      the frequencies of induced translocations are similar to those recorded in the
      classical multivalent studies, suggesting equal scoring efficiencies in both
      systems.

PMID- 8528589
TI  - Meiosis in the leek (Allium porrum L.) revisited. I. Prophase I pairing.
AB  - Meiotic chromosome pairing of the tetraploid species Allium porrum, the
      cultivated leek, was analysed by electron microscopy of 83 surface-spread nuclei
      in the late zygotene to early diplotene interval of prophase I, from four
      different varieties. Prophase I quadrivalent frequency, at 71%, marginally but
      significantly exceeds the two-thirds expected on a simple random end-pairing
      model, suggesting that more than two autonomous pairing sites occur, in some
      tetrasomes at least. This pattern of synaptic behaviour is consistent with an
      autotetraploid status, but comparison with other tetraploids, including other
      Allium species, indicates that Allium porrum may be a weak segmental
      allopolyploid displaying limited preferential homologous pairing. The incidence
      of pairing partner switches (PPSs) in prophase I quadrivalents is relatively low;
      90% of all analysed quadrivalents had only one or two PPSs. The positional
      distribution of PPSs along quadrivalents was distinctly uneven with peaks in mid
      chromosome arms and reduced frequencies around centromeres and near the ends. The
      four different varieties of leek analysed were remarkably similar in their
      meiotic behaviour despite their diverse breeding history, but individual plants
      within varieties displayed substantial variation in quadrivalent and PPS
      frequencies.

PMID- 8528590
TI  - Chromosome banding and synaptonemal complexes in Leporinus lacustris (Pisces,
      Anostomidae): analysis of a sex system.
AB  - Leporinus lacustris had been studied previously, and shows 2n = 54 metacentric
      and submetacentric chromosomes, including an XX/XY system described on the basis
      of Giemsa-stained preparations. However, there was some doubt regarding the
      identification of the sex chromosomes, because of the relative homogeneity of
      this species karyotype. Thus, the main goal of the present study was to find new
      evidence of heteromorphic sex chromosomes in these fish through chromosome
      banding and synaptonemal complex analyses. In fact, the data obtained do not
      support the presence of sexual heteromorphism. The importance of these
      methodologies in the study of fish sex chromosomes is discussed.

PMID- 8528591
TI  - Detection of rDNA sites in sugarcane by FISH.
AB  - Hybridization sites of an rDNA probe coding for the 5.8S, 18S and 26S genes were
      detected on the chromosomes of sugarcane and a related genus, Erianthus, using
      fluorescence in situ hybridization. One unpaired and five paired hybridization
      sites were detected in a Saccharum spp. hybrid. A first introgression hybrid (I1)
      between Saccharum officinarum and Saccharum spontaneum had seven pairs of
      hybridization sites. A clone of Erianthus arundinaceus showed six hybridization
      sites in somatic tissue.

PMID- 8528592
TI  - Protein folds and functional similarity; the Greek key/immunoglobulin fold.
AB  - Investigations on a number of proteins in the Greek key/immunoglobulin superfold
      group using computer methods suggested that proteins containing modified Greek
      keys might exhibit some protein-protein interactions similar to those seen with
      immunoglobulins. The two domain beta-sheet modified Greek key structure of the
      beta/gamma-crystallins is shared by other proteins, for example the chaperone
      protein PapD. Based on computer analysis, we tested for protein-protein
      interactions using protein A from Staphylococcus aureus, and showed that gamma
      crystallin, unlike alpha- or gamma s-crystallin, exhibits weak protein A binding.
      beta-Crystallin exhibits much weaker binding than gamma-crystallin. Protein A
      interaction may involve hydrophobic interactions around the interconnecting
      peptide region. We discuss the implications for the molecular evolution of the
      crystallins, the superfold, and for the molecular interactions in the mammalian
      lens that could be important in maintaining transparency.

PMID- 8528593
TI  - Mast cells in the cytokine network: the what, where from and what for.
AB  - The basic understanding of mast cell ontogeny and function has been fundamentally
      changed in recent years with observations that the cells produce and respond to a
      broad range of cytokines. These rapidly accruing data and their potential
      significance were discussed at the recent symposium "Mast Cells in the Cytokine
      Network", and the overview lectures of most speakers are summarized in this
      special journal issue. In the present introductory manuscript, the organizers of
      the meeting discuss data fundamental to an understanding of the topic and
      highlight aspects of special interest. They consider mast cells to be defined
      most reliably by their unique ultrastructure since the cells are highly
      heterogeneous in dependence of the species studied, their tissue location, their
      stage of development and probably also in relation to cytokines. Most other
      characteristics of mast cells are shared with diverse other cell types. Murine
      mast cell development is induced by several cytokines. These factors are mostly
      ineffective in human cells except for stem cell factor which causes mast cell
      development from CD34+/c-kit+ progenitors. There is however recent evidence that
      fibroblasts and keratinocytes produce additional growth factors for human mast
      cells. Regarding cytokine secretion, most molecules known so far are produced by
      both murine and human mast cells. The cells furthermore bear receptors for
      several cytokines, enabling them to respond in an autocrine and paracrine
      fashion. Mast cells may thus function within a complex cytokine network,
      affecting physiological as well as immunological and inflammatory processes.

PMID- 8528594
TI  - Mast cell ontogeny and apoptosis.
AB  - The regulation of tissue mast cell number depends both on the rate of production
      of mast cell precursors from bone marrow and the length of survival of mature
      mast cells within tissues. Mast cells develop from bone marrow under the
      influence of both interleukin-3 (IL-3) and the c-kit ligand, also known as stem
      cell factor (SCF). In humans, the mast cell precursor is CD34+, FcERI-. Mast cell
      precursors with time become less responsive to IL-3 and more responsive to SCF.
      Mast cell proliferation directed by SCF is enhanced by other cytokines including
      both IL-4 and IL-10. Once mast cell precursors target to tissues, their survival
      may largely be dependent upon the local production of SCF. Withdrawal of IL-3 or
      SCF results in mast cell apoptosis; SCF rescues mast cells following IL-3
      withdrawal. TGF-beta prevents this SCF rescue. Engagement of extracellular matrix
      by integrin receptors may also effect mast cell numbers. Thus, in the final
      analysis, mast cell numbers, while relatively constant in the normal state, may
      be up-regulated by altering the rate of their production centrally or length of
      survival in the periphery.

PMID- 8528595
TI  - Direct and indirect receptor-independent G-protein activation by cationic
      amphiphilic substances. Studies with mast cells, HL-60 human leukemic cells and
      purified G-proteins.
AB  - Studies from several laboratories have revealed that structurally diverse
      substances including the wasp venom, mastoparan (MP), activate purified
      regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins) in a
      receptor-independent manner, presumably by mimicking the effects of heptahelical
      receptors. Mast cells and differentiated HL-60 human leukemic cells are useful
      model systems for the analysis of receptor-independent G-protein activation. We
      compared the effects of 2-phenylhistamines which are cationic-amphiphilic, too,
      and of MP on G-protein activation in dibutyryl cAMP-differentiated HL-60 cells
      and in the rat basophilic leukemia cell line, RBL 2H3. In HL-60 cells, 2
      phenylhistamines show stimulatory effects which resemble those of formyl peptide
      receptor agonists but which cannot be attributed to agonism at classical
      receptors. 2-phenylhistamines do not, however, activate RBL 2H3 cells and various
      other myeloid cell types, pointing to cell type-specificity of receptor
      independent G-protein activation. In HL-60 cells, MP shows effects on G-protein
      activation which differ substantially from those of formyl peptides. In RBL 2H3
      membranes, MP shows similar effects on G-protein activation as in HL-60
      membranes. We develop a model according to which receptor-independent G-protein
      activation can be subdivided into direct and indirect receptor-independent G
      protein activation. In case of the former mechanism, substances like 2
      phenylhistamines interact with G-protein alpha-subunits and in case of the latter
      mechanism, substances like MP interact with nucleoside diphosphate kinase which
      catalyzes the formation of GTP. This newly formed GTP is then transferred to, and
      cleaved by, G-protein alpha-subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528597
TI  - Cytokine secretion by human mast cells.
AB  - Mast cells have been traditionally viewed as effector cells of immediate-type
      hypersensitivity reactions. Besides this, mast cell activation and degranulation
      have been associated with various biologically and clinically important
      functions. Results of the past few years suggest that mast cells are involved in
      the development of late-phase reactions and influence other chronic inflammatory
      responses through the generation and secretion of various multipotential
      cytokines.

PMID- 8528596
TI  - Mouse mast cell cytokine production: role in cutaneous inflammatory and
      immunological responses.
AB  - The role of mast cells in cutaneous physiology and pathology has long been a
      subject of intense speculation and great clinical interest. In this brief review,
      which is focused primarily on murine systems, we outline certain important
      aspects of the biology of the mast cell, including their ability to produce a
      variety of cytokines, describe the development of a model system (the "mast cell
      knock-in mouse") for studying the roles of cutaneous mast cells in biological
      responses in vivo, and illustrate a few examples of how this approach has been
      used to investigate the contributions of mast cells and their cytokines to
      cutaneous inflammatory or immune responses.

PMID- 8528598
TI  - Cytokines involved in growth and differentiation of human basophils and mast
      cells.
AB  - Mast cells and basophils are multifunctional effector cells of the immune system.
      Both are myeloid cells and originate from multipotent hemopoietic progenitor
      cells. Usually, human basophils complete their differentiation in the bone
      marrow. In contrast, mast cells usually undergo differentiation in extramedullary
      organs. During the past few years, growth factors for human basophils and a
      growth factor for human mast cells have been identified. Interleukin-3 is the
      most potent differentiation factor for human basophils and activates mature
      basophils via high affinity binding sites. Other basophil agonists are GM-CSF, IL
      5, NGF and certain chemokines (IL-8, MCP-1). Mast cells apparently loose cytokine
      binding sites during mastopoiesis and as mature cells, do not express detectable
      amounts of IL-3R, GM-CSFR or IL-8R. However, in contrast to other myeloid cells,
      mast cells express SCF receptor/c-kit during mastopoiesis and on mature cells.
      Furthermore, the ligand of c-kit, SCF, induces differentiation of human mast
      cells from their progenitor cells and upregulates effector functions in mature
      mast cells.

PMID- 8528599
TI  - Chemokines and the allergic response.
AB  - The beta subfamily of chemokines contains cytokine-like factors which are
      chemotactic for human basophils and eosinophils. The also stimulate these cells
      to secrete pro-inflammatory substances such as histamine or eosinophil cationic
      protein. MCAF/MCP-1, MCP-2, MCP-3, RANTES and MIP-1 alpha all attract and
      stimulate basophils; MCP-1 and MCP-3 are the most potent. RANTES, MCP-3 and to a
      lesser degree MIP-I alpha are chemotactic factors and activators of eosinophils.
      Cytokines such as IL3, IL5 and GM CSF can augment the responses of these cells to
      the various chemokines and function as primers. These substances may have
      particular importance as mediators of allergic inflammation, particularly the
      late phase component of the response.

PMID- 8528600
TI  - Mast cells as modulators of hair follicle cycling.
AB  - While the central role of mast cells (MC) in allergy and inflammation is well
      appreciated, much less is known about their physiological functions. The
      impressive battery of potent growth modulatory MC products, and increasing
      evidence of MC involvement in hyperproliferative and fibrotic disorders suggest
      that tissue remodelling may be one of those, namely in the skin. Here, we
      delineate why this may best be studied by analysing the potential role of MC in
      hair growth regulation. On the background of numerous, yet widely under
      appreciated hints from the older literature, we summarize and discuss our recent
      observations from the C57BL/6 mouse model for hair research which support the
      concept that MC are functionally important modulators of hair follicle cycling,
      specifically during anagen development. This invites to exploit the murine hair
      cycle as a model for dissecting the physiological growth modulatory functions of
      MC and encourages the exploration of MC-targeting pharmaceutical strategies for
      the treatment of hair growth disorders.

PMID- 8528601
TI  - Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist
      decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell
      lines.
AB  - Mast cells and basophils are central effector cells of allergic reactions and are
      involved in inflammatory diseases. These cell types produce an array of mediators
      including a broad spectrum of cytokines. In order to examine whether antiallergic
      drugs modulate the release of these mediators, we have investigated the influence
      of dexamethasone and decarboethoxy-loratadine (DEL), the active metabolite of the
      H1-blocking agent loratadine, on the release of IL-6 and IL-8 by the human mast
      cell line HMC-1 and the human basophilic cell line KU812 by ELISA. Dexamethasone
      (10(-6)-10(-11) M) or Del (10(-5)-10(-14) M) were added to the cells either 1 h
      prior to or simultaneously with PMA and Ca-ionophore A23187. When preincubated
      with the cells, DEL dose-dependently suppressed IL-6 release by up to 40% and IL
      8 release by up to 50%. Dexamethasone potently suppressed secretion of both
      cytokines if simultaneously added to the cells with the stimuli by up to 60% and
      after preincubation by up to 80%. Since both antihistamines and glucocorticoids
      are used for treatment of allergic diseases, the findings reported here indicate
      that these drugs may modulate allergic reactions via inhibition of cytokine
      release from mast cells and basophils.

PMID- 8528602
TI  - Cytokine treatment of mast-cell-mediated skin diseases.
AB  - Cytokines released by mast cells as well as their effects on mast cell functions
      appear to be of major importance in the pathogenesis of mast cell mediated skin
      diseases. In addition, the identification of some key mediators which were found
      to play a crucial in vivo role in certain disease states may allow the
      development of new therapeutic strategies using cytokines or cytokine antagonists
      for the treatment of inflammatory skin diseases. So far, encouraging results have
      been obtained when diseases with mast cell involvement such as atopic eczema or
      mastocytosis have been treated with different IFNs. Future trials using IFNs and
      other newly detected cytokines or their antagonists are required to establish
      effective therapy regimens.

PMID- 8528603
TI  - The regulatory functions of the rolB and rolC genes of Agrobacterium rhizogenes
      are conserved in the homologous genes (Ngrol) of Nicotiana glauca in tobacco
      genetic tumors.
AB  - To compare patterns of expression between the Ngrol genes of N. glauca and the
      Rirol genes of Agrobacterium rhizogenes, we performed fluorometric and
      histochemical analysis of transgenic genetic tumors on the hybrid of Nicotiana
      glauca x N. langsdorffii (F1) that harbored a beta-glucuronidase (GUS) reporter
      gene fused to the promoter of NgrolB, NgrolC, RirolB or RirolC. The promoters of
      NgrolB and NgrolC had 2- to 3-fold lower activity than those of RirolB and
      RirolC. However, the changes in patterns of GUS activity caused by deletion of
      NgrolB and NgrolC promoters were similar to those of RirolB and RirolC promoters.
      This result suggests that the cis-acting sequences that regulate the level of
      expression of RirolB and RirolC are conserved in the NgrolB and NgrolC promoters.
      Furthermore, an auxin dependent (NAA-dependent) increase in GUS activity was
      observed in the case of NgroB-GUS and RirolB-GUS. Histochemical analysis showed
      GUS activity encoded by both NgrolB-GUS and RirolB-GUS in normal-type F1
      transgenic plants was located in meristematic zones, while that encoded by NgrolC
      GUS and RirolC-GUS was detected mainly in vascular systems of various organs.
      Thus, the patterns of expression of the Ngrol genes were the same as those of the
      Rirol genes in terms of promotion by auxin and tissue-specificity, indicating
      that regulatory mechanisms for both sets of genes have been conserved during the
      evolution of the genus Nicotiana after transfer from a progenitor of
      Agrobacterium to that of Nicotiana.

PMID- 8528604
TI  - Molecular cloning and characterization of Rosa hybrida dihydroflavonol 4
      reductase gene.
AB  - A full length cDNA clone encoding rose dihydroflavonol 4-reductase (DFR) was
      isolated from a cDNA library derived from rose petals by screening with the cDNA
      of Petunia hybrida DFR. Sequence comparison of the rose DFR with reported DFR
      genes revealed that they are homologous to each other. The amount of DFR mRNA in
      rose petals was developmentally regulated and paralleled anthocyanin production
      in petals. Sepals, thorns, styles and stamens also contained anthocyanins and DFR
      mRNA. No DFR mRNA was observed in mature leaves and a small amount of the
      transcript was detected in young leaves. A petunia cultivar, whose colour was
      pale pink due to a deficiency in flavonoid 3'-hydroxylase and flavonoid 3',5'
      hydroxylase, was transformed with a binary vector containing a rose DFR cDNA
      cloned behind a constitutive promoter. Petals and anthers of the resultant
      transgenic petunia plants were salmon pink and contained pelargonidin, an
      anthocyanidin rarely found in petunia.

PMID- 8528605
TI  - Three protein fractions that bind to a narrow region of the promoter of the
      ribosomal RNA gene in Vicia faba.
AB  - We previously described the preparation of a protein fraction that bound to the
      promoter region of the rRNA gene of Vicia faba. We now describe two additional
      protein fractions that interact with this DNA element. The three protein
      fractions have similar binding properties with the exception of their binding
      stabilities. DNase I footprinting experiments revealed that these protein
      fractions bind to a region that is located about 60 bp upstream from the site of
      initiation of transcription. From methylation interference experiments and gel
      retardation assays with mutated oligonucleotides, it was evident that the protein
      fractions required the same residues for the formation of stable DNA-protein(s)
      complexes. However, the three protein fractions were chromatographically
      distinguishable and the stability of their binding to DNA was different. Although
      the functions of these fractions are still unknown, the fact that several protein
      fractions can bind to a narrow region near the site of initiation of
      transcription is of considerable interest in terms of the mechanism of
      transcription of the rRNA gene.

PMID- 8528606
TI  - Different sets of cis-elements contribute to the expression of a catalase gene
      from castor bean during seed formation and postembryonic development in
      transgenic tobacco.
AB  - Deletion analysis of the promoter region of a gene for catalase, cat2, from
      castor bean (Ricinus communis) was performed to identify the cis-regulatory
      elements responsible for the expression of a beta-glucuronidase (GUS) fusion gene
      during seed formation and postembryonic development in transgenic tobacco. The
      analysis showed that multiple cis-elements contribute to the activity of the cat2
      promoter during seed formation and postembryonic development. The 5'-upstream
      regions from -1,241 to -816 bp, from -720 to -682 bp, and from -632 to -535 bp,
      relative to the site of initiation of translation of cat2, contributed positively
      to the activity of the cat2 promoter during both stages. By contrast, the region
      from -816 to -720 bp had a negative effect at both stages. The region from -682
      to -632 bp contributed positively to the activity during seed formation but
      negatively during postembyonic development. Histochemical analysis revealed that
      the multiple cis-elements determined not only the level of expression of the
      chimeric gene but also the tissue-specificity of such expression. For example,
      the region from -1,241 to -816 bp allowed expression of the chimeric gene in the
      axis of the embryo of the dry seed, as well as in the cortex of the middle part
      of the hypocotyl and at the base of epicotyl in the young seedling.

PMID- 8528607
TI  - Structure of a gene subunit 9 of NADH dehydrogenase (nad9) in rice mitochondria
      and RNA editing of its transcript.
AB  - We identified a gene for subunit 9 of NADH dehydrogenase (nad9) in rice
      mitochondrial DNA. Southern and Northern hybridizations demonstrated that rice
      nad9 is present in a unique region in mtDNA and is transcribed at a high level.
      The transcript of rice nad9 is edited at twelve positions.

PMID- 8528608
TI  - A novel isoenzyme of ascorbate peroxidase localized on glyoxysomal and leaf
      peroxisomal membranes in pumpkin.
AB  - A novel isoenzyme of ascorbate peroxidase with molecular mass of 31 kDa was found
      to be localized on membranes of microbodies. Intact microbodies had no latent
      ascorbate peroxidase activity, an indication that the active site of the
      ascorbate peroxidase was exposed to the cytosol and the peroxidase would scavenge
      hydrogen peroxide leaked from microbodies.

PMID- 8528609
TI  - The gene for pyruvate, orthophosphate dikinase in C4 plants: structure,
      regulation and evolution.
AB  - Pyruvate, orthophosphate dikinase (PPDK; EC 2.7.9.1) is a key enzyme in
      photosynthesis in plants that exploit the C4 photosynthetic pathway for the
      fixation of CO2. This review focuses on the structure, regulation and evolution
      of the C4-type ppdk gene in the maize genome. The C4-ppdk gene in maize consists
      of 19 exons spanning about 12 kbp. The gene is transcribed from two different
      initiation sites under the control of two promoters to produce two mRNAs of
      different sizes. The larger one contains the exon 1 sequence that encodes the
      chloroplast transit peptide and its product acts as C4-PPDK in chloroplasts,
      while the smaller one does not contain the sequence and its product may function
      as a C3-enzyme in the cytosol. This unusual dual promoter system is not unique to
      the maize C4-type ppdk gene since the same organization is also observed in the
      rice (C3 plant) ppdk gene and in Flaveria. Thus, the two-promoter system is
      common to plant ppdk genes from C3 and C4, monocot and dicot plants. A discussion
      is also presented of the generation of a system for regulation of the expression
      of the C4-type ppdk gene. A chimeric gene consisting of a reporter gene under the
      control of the promoter of maize C4-ppdk is exclusively expressed in
      photosynthetic tissues and not in roots or stems of transgenic rice. The
      expression of the introduced gene is also regulated by light: it is low in
      etiolated leaves and is enhanced by illumination. These results indicate that the
      regulatory system that controls ppdk expression in maize is not unique to C4
      plants.

PMID- 8528610
TI  - Phospholipase D from soybean (Glycine max L.) suspension-cultured cells:
      purification, structural and enzymatic properties.
AB  - Phospholipase D (phosphatidylcholine phosphatidohydrolase EC 3.1.4.4) from
      soybean (Glycine max L.) suspension-cultured cell was purified around 1,200-fold
      to homogeneity by acetone precipitation, Macro-Prep High Q anion exchange, and
      octyl-Sepharose CL-4B affinity chromatography. The purified enzyme released 1,600
      mumol of choline per min per mg of protein. The enzyme is monomeric with a
      molecular mass of 92 kDa, as estimated by SDS-PAGE. One of the most interesting
      characteristics of the purified soybean phospholipase D was the dependence of the
      pH optimum on the Ca2+ ion concentration in the assay. With 10 mM, 20 mM and 40
      mM Ca2+ ions, the optima were at pH 7.5, 6 and 5.5, respectively. The specific
      adsorption of phospholipase D onto octyl-Sepharose gel suggests that the molecule
      becomes more hydrophobic in the presence of Ca2+ ions. The amino acid sequence of
      the first 18 N-terminal residues of soybean phospholipase D revealed a high
      degree of homology with those previously published for cabbage leaf and castor
      bean endosperm enzymes. Western blots of the soybean phospholipase D showed an
      immunoreactivity with antibodies raised against a synthetic peptide corresponding
      to the 15 N-terminal amino acid residues of phospholipase D from cabbage leaves.

PMID- 8528611
TI  - Sexual potency and adaptive mutation in bacteria.

PMID- 8528612
TI  - Virulence factors of Cryptococcus neoformans.
AB  - Cryptococcosis is a serious fungal disease in patients with AIDS or other defects
      in T-cell-mediated host defenses. Cryptococcus neoformans produces several
      virulence factors, most notably the polysaccharide capsule and phenol oxidase.
      Molecular studies of cryptococcal virulence factors have contributed to our
      understanding of the pathobiology of this yeast, and will enable the
      identification of new targets for antifungal therapy.

PMID- 8528613
TI  - Lactococcal bacteriocins: mode of action and immunity.
AB  - Bacteriocins are antimicrobial peptides produced by bacteria. Some of those
      synthesized by Lactococcus lactis have been characterized in great detail
      recently. The lactococcal bacteriocins are hydrophobic cationic peptides, which
      form pores in the cytoplasmic membrane of sensitive cells.

PMID- 8528614
TI  - Phenotypic variation of carbohydrate surface antigens and the pathogenesis of
      Haemophilus influenzae infections.
AB  - Phenotypic variation of two major carbohydrate surface antigens of Haemophilus
      influenzae, the capsule and lipopolysaccharide, exemplifies some of the genetic
      mechanisms used by pathogenic bacteria in interacting with host
      microenvironments. The ability to generate phenotypic variety at high frequency
      within clonal populations of microorganisms provides an adaptive mechanism to
      combat the polymorphisms and immune repertoires of the host.

PMID- 8528615
TI  - Environmental modulation of gene expression and pathogenesis in Yersinia.
AB  - The yersiniae are a useful model for understanding how environmental modulation
      of gene expression allows pathogens to inhabit a wide range of niches. This
      review follows the enteropathogenic yersiniae, Yersinia enterocolitica and
      Yersinia pseudotuberculosis, and the agent of plague, Yersinia pestis, through
      their life cycles, describing how adaptive gene expression may promote successful
      pathogenesis.

PMID- 8528616
TI  - Role of YadA in Yersinia-enterocolitica-induced reactive arthritis: a hypothesis.

PMID- 8528617
TI  - The nonspecific nature of endotoxin tolerance.
AB  - Re-exposure of organisms or cells to endotoxin after a previous challenge is not
      accompanied by the profound metabolic changes that are induced by the first
      encounter with endotoxin. Endotoxin tolerance is not specific to the action of
      lipopolysaccharide, and crossreactivity with other exogenous stimuli occurs.
      Various cytokines can mimic the effects of endotoxin in vivo and/or in vitro.

PMID- 8528618
TI  - Human herpesvirus 6 as a potential copathogen.
AB  - The molecular, biological and immunological studies of the recently identified
      human herpesvirus 6 (HHV-6) suggest that the virus is involved in the etiology of
      at least three lymphoproliferative diseases. Furthermore, HHV-6 may be an
      important cofactor in the pathogenesis of several other diseases, including HIV
      associated disease and some cancers, but further investigation is needed to
      establish a causal relationship.

PMID- 8528619
TI  - The search for virulence determinants in Aspergillus fumigatus.
AB  - The development of aspergillosis in an immunodeficient host depends on
      interactions between fungal and host components. The recognition by Aspergillus
      fumigatus of fibrinogen and laminin, and the secretion of extracellular
      proteinases and ribonucleotoxin have been suggested to mediate adherence to
      mucosal surfaces and subsequently to bring about host-tissue invasion.

PMID- 8528620
TI  - Studies on cercariae from the Kuwait Bay. VI. Description and surface topography
      of Cercaria kuwaitae VI sp. n. (Trematoda: Haplosplanchnidae).
AB  - A new haplosphlanchnid cercaria, Cercaria kuwaitae VI sp. n., was found in the
      prosobranch snail Cerithidea cingulata in the Kuwait Bay. Details are presented
      on the morphology and behavior of the cercaria and the encystment process. The
      new cercaria is a biocellate, distome, with a prominent single sac-like
      intestinal cecum extending well posterior to the ventral sucker and develops in
      simple sporocysts. It differ from known haplosplanchnid cercariae in the absence
      of finger-like processes on the tail, and the presence of V-shaped excretory
      vesicle extending beyond ventral sucker and the presence of cervical glands. The
      surface topography of the cercaria and its sporocyst is examined by scanning
      electron microscopy. This is the first haplosplanchnid cercaria to be described
      from a Cerithidea species.

PMID- 8528621
TI  - Localization of actin and myosin in Cryptosporidium parvum using immunogold
      staining.
AB  - The location of actin and myosin of the several stages of Cryptosporidium parvum
      was observed. The tissue antigen of C. parvum was prepared through
      immunosuppression of ICR mice with Depomedrol. The thin sectioned specimens,
      which were incubated with the IgG fraction of the rabbit polyclonal antibodies
      raised against chicken back muscle actin and bovine uterus myosin, were treated
      with 10 nm gold-conjugated goat anti-rabbit IgG. Electrodense particles were
      located mainly on the pellicles of all observed developmental stages of the
      parasites. The number of actin gold particles in the cytoplasm increased when the
      parasite was dividing actively as in case of meronts. Especially in
      macrogametocytes, a lot of actin and myosin particles were synthesized and
      storaged as amilopectin-like bodies. There were many actin gold particles along
      the microspikes of cytoplasmic membranes in various developmental stages. The
      actin and myosin observed in this study may play important roles to control the
      shape of the parasites and movements of cytoplasmic membranes as cytoskeletal
      proteins.

PMID- 8528622
TI  - TEM ultrastructure of the tegumental layer of Gymnophalloides seoi (Digenea:
      Gymnophallidae).
AB  - A transmission electron microscopic study was performed on the ultrastructure of
      the tegumental layer of Gymnophalloides seoi (Digenea: Gymnophallidae)
      metacercariae and adults. The metacercariae were obtained from naturally infected
      oysters, Crassostrea gigas, and the adults from experimentally infected C3H mice.
      The tegumental layer generally revealed a small number of foldings, numerous
      small vacuoles, sines, and muscle bundles. Beneath the muscle layer, nuclei of
      the tegumental cells were located. There was little difference in the structure
      of the tegument between the metacercariae and adults. The oral sucker, having
      well-developed muscle layers, showed a similar structure to the ventral sucker
      except numerous foldings in the ventral sucker. The ventral pit was surrounded by
      a thin syncytial layer, where a number of microtubules and mitochondria were
      seen. Around the ventral pit located well-developed circular and longitudinal
      muscles. The results showed that the ultrastructure of the tegumental layer of G.
      seoi metacercariae and adults revealed little difference from other trematodes in
      general. The ventral pit, a peculiar structure of this trematode, seems to
      function as a sphincter or an accessory adhesive organ.

PMID- 8528623
TI  - Effects of gamma-irradiation on intracellular proliferation of Toxoplasma gondii
      RH tachyzoites.
AB  - A quantitative assay was performed on the effects of gamma-irradiation (30-300
      Gy) on intracellular proliferation of Toxoplasma gondii RH tachyzoites in human
      leukemic HL-60 cells and murine peritoneal macrophages by means of 3H-uracil
      uptake assay. Infected non-irradiation group (NI) and uninfected group
      (incubating only host cells) were prepared. The 3H-uracil uptake by tachyzoites
      of NI group 12-24 hrs after infection was 2,190-4,787 counts per minute for
      macrophages and 2,967-8,254 for HL-60 cells, whereas the irradiated tachyzoites
      revealed only 381-703 (100 Gy) and 218-408 (300 Gy) for macrophages, and 1,911
      2,618 (30 Gy), 1,253-1,384 (70 Gy), 1,013-1,090 (100 Gy), and 483-588 (300 Gy)
      for HL-60 cells. The proliferation inhibition rate was similar in macrophages and
      HL-60 cells, for example, 89-94% and 80-94% respectively by 300 Gy, 12-24 hrs
      after infection. It is concluded that RH tachyzoites of T. gondii are severely
      affected by gamma-irradiation in their capability of intracellular proliferation.

PMID- 8528624
TI  - [Gastric anisakiasis cases in Cheju-do, Korea].
AB  - Human anisakiasis may occur after ingestion of raw marine fish infected with
      nematode larvae of Anisakidae. Anisakiasis caused by the migration of the larva
      into the wall of stomach, small intestine and other portion has been reported in
      Korea. This prospective study was made of all cases referred to parasitological
      laboratory in Cheju-do between June 1989 and June 1992. Gastric anisakiasis was
      confirmed if larvae invading the gastric wall were observed by gastrofiberscopy.
      One hundred and seven cases were diagnosed, most of which were in 30-49 years
      old. Most of the patients complained acute epigastric pain with history of eating
      raw marine fish. This symptom usually occurred about 12 hours to 1 day after
      ingestion of infected marine fish. Edema, erosion or ulcer of the mucosa and
      hemorrhage from the gastric wall were observed in the involved areas. Ninety
      larvae removed from the stomach were identified; the larva of Anisakis simplex
      was the most prevalent species, and the larva of Pseudoterranova decipiens was
      also detected. The important species of marine fish from which the patients
      became infected was demonstrated as yellow corvina, sea eel, ling, cuttle fish,
      yellowtail and others. Five species of marine fish as a possible source of
      infection were examined, and Anisakis simplex larvae and Pseudoterranova
      decipiens larvae were collected from the mackerel and rock cod. This study
      demonstrates that anisakiasis is recognized as a public health problem in Korea.

PMID- 8528625
TI  - Immunoblot analysis for serum antibodies to Pneumocystis carinii by age and
      intensity of infection in rats.
AB  - The present study aims to observe changing patterns of serum antibody to
      Pneumocystis carinii in normal rats of different ages and in immunosuppressed
      rats. The serum IgG antibody was observed by immunoblotting with crude antigen of
      P. carinii which were purified from the lungs of infected rats. The crude
      antigens separated in SDS-PAGE resolved more than 20 protein bands from 20 to 200
      kDa. Of them, 40-45, 50-55, 116 and 200 kDa bands were major antigens of P.
      carinii. Most of the normal rats of up to 4 weeks had the antibodies reacting the
      4 bands, but none of 8-week-old rats revealed the specific antibody. After the
      rats grew for 40 weeks, all were found to have the antibody in their serum. Same
      pattern of serum antibody level by age was found in ELISA. When immunosuppressed
      rats became heavily infected, the antibody in their serum decreased
      distinctively. The present results suggest that antibodies in normal newborn rats
      are transferred from their mother and lowered up to 8 weeks. Thereafter, the
      levels of the antibodies begin to increase by natural exposure to P. carinii. It
      was also confirmed that the intensity of P. carinii infection is inversely
      related with levels of serum antibodies.

PMID- 8528626
TI  - Inhibition of Con A-induced lymphocyte proliferation by peritoneal exudate of
      Toxoplasma gondii-infected mice.
AB  - The presence of biological response modifiers (BRM)-like effect was confirmed in
      peritoneal exudate (PE) of Toxoplasma gondii-infected ICR mice which inhibited
      Concanavalin A (Con A)-induced peritoneal lymphocyte (PL) proliferation. During 5
      days of PL incubation with 10 micrograms/ml Con A with or without PE, 3H
      thymidine uptake was measured for the last 24 hrs. Compared to uninduced control,
      PL proliferated by 7.3-fold with Con A induction. When PE of infected mice was
      added, PL proliferation was inhibited by 74.0 +/- 11.9% whereas inhibition by PE
      of normal mice was 16.4 +/- 8.3%. Inhibitory effect of PE increased exponentially
      from 3 days up to 4-5 days of survival after the infection. Inhibitory activity
      of PE was decreased concentration-dependently. Also the inhibition was diminished
      when the PE was treated with heat of 95 degrees C for 10 min or precipitated with
      10% trichloracetic acid (TCA). In SDS-PAGE of PE, many minor bands appeared
      newly. Heat-labile protein molecule in PE exerted inhibitory activity to Con A
      induced lymphocyte proliferation.

PMID- 8528627
TI  - [Detection of Toxoplasma antigens and antibodies in mice infected with different
      strains of Toxoplasma gondii].
AB  - This study aims to assess the possible strain-dependent variations in detection
      of Toxoplasma antigens and antibodies. The virulent RH strain or avirulent
      Beverley strain of T. gondii were injected into mice, intraperitoneally, and
      their antigens, antibodies and parasites were identified from the blood or
      tissues; liver, brain and spleen by ELISA, Western blot and PCR. In mice infected
      with RH strain, circulating antigens and parasitemia were first detected from 2
      days after infection, and Toxoplasma DNA were found in the blood, liver, brain
      and spleen from 3 days after infection. It was impossible to detect specific IgM
      and IgG antibodies to T. gondii, and any specific band was not found by Western
      blot. In mice infected with Beverley strain, circulating antigens were detected
      between day 10 and day 35. The Toxoplasma DNA was found in the blood and liver
      from day 15 until day 60, and in the brain from day 20. But Toxoplasma DNA in the
      spleen were mainly detected between day 10 and day 30. The IgM antibodies were
      first appeared on day 10 post-infection, and were noted obviously increased
      between day 15 and 25. The IgG antibodies were first detected on day 15, and
      showed progressively increased titers. The antibody binding bands were specific
      according to infection period. Sera from mice infected with Beverley strain
      reacted mainly with the antigen of 27.5-kDa and 32.5-kDa. In conclusion, mice
      infected with RH strain revealed Toxoplasma antigens strongly, but not
      antibodies. However, mice infected with Beverley strain revealed both the
      Toxoplasma antigens and antibodies. The present results showed that immune
      responses are different between avirulent and virulent T. gondii.

PMID- 8528628
TI  - Cytotoxicity of a cysteine proteinase of adult Clonorchis sinensis.
AB  - To clarify the correlation of the proteinase activity with pathogenicity of
      Clonorchis sinensis, the proteinase activity either in excretory-secretory
      products (ESP) or in crude extracts of adult C. sinensis was examined. Substrate
      gel electrophoresis of the ESP and crude extracts revealed four distinct enzyme
      bands, which were differently inhibited by the specific proteinase inhibitors.
      The proteinase of the ESP with molecular mass of 24 kDa, was purified 23-fold
      with 14.5% yield by spectra gel ACA 44 gel filtration. It exhibited optimal pH at
      7.5 in sodium phosphate (0.1 M). Its activity was inhibited specifically by N
      ethylmaleimide (NEM) and antipain whereas potentiated 1.9 folds in the presence
      of 5 mM dithiothreitol (DTT). Cytotoxicity of the proteinase increased in a dose
      dependent manner up to 120 micrograms/ml while reduced by NEM and antipain,
      indicating that cysteine proteinase was responsible for the cytotoxicity. This
      result shows that the 24 kDa cysteine proteinase is deeply correlated with the
      pathogenicity of C. sinensis infection.

PMID- 8528629
TI  - The first human case of Clinostomum complanatum (Trematoda: Clinostomidae)
      infection in Korea.
AB  - The authors present the first human case of Clinostomum pharyngitis in Taegu,
      Korea. The patient was a 56-year old male who visited an otolaryngology clinic
      due to foreign body sensation and pain of the pharyngeal region for 3-4 days. He
      used to eat raw fresh-water fish. Otolaryngological examinations revealed a
      living worm adhered to the right posterior pharyngeal wall. The worm removed was
      identified as C. complanatum after morphological observations. It is likely that
      more attention should be paid to eating raw fresh-water fish in Korea with
      regards to Clinostomum pharyngitis.

PMID- 8528630
TI  - The first human case of Diplogonoporus balaenopterae (Cestoda:
      Diphyllobothriidae) infection in Korea.
AB  - The first human case of Diplogonoporus balaenopterae infection is reported in
      Korea. The patient was a 41-year old male who passed a part of cestode strobila,
      about 1 m long, spontaneously in his stool. He used to eat raw marine fish when
      he drank alcohol. The worm was identified as D. balaenopterae after morhological
      observations and literature review. Results of laboratory examination were within
      normal limits except for slight eosinophilia (6%) and extraordinarily high serum
      Ig E level (10,182 IU/ml).

PMID- 8528631
TI  - Recovery of Pseudoterranova decipiens (Anisakidae) larvae from codfish of the
      Antarctic Ocean.
AB  - Anisakid larvae were found from the liver and stomach of the codfish (Notothenia
      neglecta) caught from the Antarctic Ocean, South Pole, where the Polar Research
      Center of The Korea Ocean Research and Development Institute is operating.
      Through observations by scanning electron (SEM) and light microscopy (LM), they
      were identified as the third stage larvae of Pseudoterranova decipiens, a
      potential agent of human codworm anisakiasis. They measured 25.0-28.5 mm in
      length, and 0.6-0.8 mm in width. The SEM revealed a prominent boring tooth, three
      lips, and excretory pore at the anterior end, and a small but prominent mucron at
      the posterior end. From whole mounts and cross sections of the larvae the
      ventriculus, intestinal cecum and a Renette cell were found characteristically at
      the same plane. Raw eating of the codfish caught from the Antarctic Ocean near
      the South Pole should be avoided so as to prevent human codworm anisakiasis in
      this area.

PMID- 8528632
TI  - Helminths in Rattus norvegicus captured in Chunchon, Korea.
AB  - We report helminthic infections in the liver and intestine of Rattus norvegicus
      captured in Chunchon, Korea from April to October, 1994. Out of 43 examined rats,
      eggs of Capillaria hepatica were found in 11, Hymenolepis diminuta in 14 and
      Taenia taeniaeformis metacestodes in 28. Those rats can be sources of zoonotic
      infections in the surveyed area.

PMID- 8528633
TI  - A case of tick bite by a spontaneously retreated Ixodes nipponensis.
AB  - A 58-year old housewife consulted us about 1 cm sized, dark-brownish, bean-like
      mass which was dropped spontaneously from indurated skin lesion on her abdomen.
      The mass was identified morphologically as an engorged female Ixodes nipponensis.
      Nine days earlier, she had an excursion collecting edible sprouts of wild grass.
      Spontaneous retreat has been unusual in clinical tick bites in Korea. Fourteen
      cases of tick bite described in the Korean literature were reviewed briefly in
      relation to Lyme borreliosis.

PMID- 8528634
TI  - Infestation rate of head lice in primary school children in Inchon, Korea.
AB  - The survey of the head louse infestation of primary school children in Inchon
      city was carried out in May 26-27, 1995. Total number of the children surveyed
      were 1,530. Four (0.5%) out of 768 boys were infested with nits or adults/nymphs
      of lice and 72 (9.4%) out of 762 girls were positive with those of lice. The
      infestation rate of lice for girls was 19 times higher than that of boys.

PMID- 8528635
TI  - Single-agent chemotherapy versus combination chemotherapy in advanced non-small
      cell lung cancer: a quality and meta-analysis study.
AB  - STUDY OBJECTIVE: To estimate the quality of the studies and to compare single
      agent with combination chemotherapy in advanced non-small cell lung cancer.
      DESIGN: Identification of published randomized trials and extraction of essential
      results directly from the published reports. MEASUREMENTS AND RESULTS: Survival
      probability at 1 year, as estimated from the published survival curves, has been
      considered as the end-point of interest. Quality scoring of the studies has also
      been performed. Arithmetical calculation, concerning the estimation of quantities
      necessary for the meta-analysis of the literature, has been addressed. The
      estimated pooled Odds Ratio of death was 0.8, with 95% confidence interval of 0.6
      1.0, thus favoring combination chemotherapy. CONCLUSIONS: The results of our meta
      analysis favor combination chemotherapy. They must, however, be considered in the
      light of their clinical relevance and of the balance between quality of life,
      toxicity and costs of chemotherapy.

PMID- 8528636
TI  - Nuclear DNA and nuclear protein content of tumor cell in adenocarcinoma of the
      lung.
AB  - We measured DNA and protein contents of nuclei in resected tumors from 17 cases
      (six female and 11 male) of pulmonary primary adenocarcinoma. The relationship
      between the contents of nuclear DNA and protein on tumoral behavior was
      evaluated. We found that the content of nuclear DNA and protein was significantly
      higher in advanced stages than in early stages in patients with adenocarcinoma (P
      < 0.05). We also found the nuclear protein, DNA contents and the ratio of nuclear
      protein to DNA significantly higher in patients under the average age of 61 than
      in the patients over 61 (P < 0.05). Tumor size was found to be greater in Stage
      III and IV cases than Stage I cases (P < 0.05). In conclusion, it has been
      postulated that evaluation of malignant disease and its behavior might be
      simplified by measuring nuclear DNA and the protein contents of tumors,
      contributing to disease control.

PMID- 8528637
TI  - Pre-treatment prognostic factors in patients with stage III non-small cell lung
      cancer treated with hyperfractionated radiation therapy with or without
      concurrent chemotherapy.
AB  - We analyzed prognostic factors for non-small cell lung cancer (NSCLC) treated
      with hyperfractionated radiotherapy (HFX RT) with or without concurrent
      chemotherapy. One-hundred sixty-nine patients with histologically or
      cytologically proven, Stage III NSCLC, Karnofsky performance status (KPS) > or =
      50, and no previous therapy were treated in a randomized trial as follows: Group
      1--HFX RT to a total dose of 64.8 Gy (61 patients); Group 2--the same HFX RT with
      chemotherapy consisting of 100 mg of carboplatin on days 1 and 2 and 100 mg of
      etoposide on days 1-3 of each week during the RT course (52 patients); and Group
      3--the same HFX RT with chemotherapy consisting of 200 mg of carboplatin on days
      1 and 2 and 100 mg of etoposide on days 1-5 of the first, third, and fifth weeks
      of the RT course (56 patients). The median survival time for all 169 patients was
      13 months and the 5-year survival rate was 13.4%. The median time to relapse
      (local or distant) was 11 months and the 5-year relapse-free survival was 12.8%.
      Group 2 patients had a better prognosis than Group 1 patients (P = 0.0028) but
      there were no differences in prognosis between Groups 2 and 3 and between Groups
      1 and 3. Of potential prognostic factors examined, female gender (P = 0.00012),
      age > or = 60 (P = 0.00000), KPS > or = 80 (P = 0.00000), Stage IIIA (P =
      0.00000), and previous weight loss < or = 5% (P = 0.00000) were associated with
      better prognosis. These findings were confirmed by multivariate analysis.

PMID- 8528638
TI  - Adjuvant immunotherapy with interleukin 2 and lymphokine-activated killer cells
      after noncurative resection of primary lung cancer.
AB  - A randomized controlled study of immunotherapy with interleukin 2 (IL-2) and
      lymphokine-activated killer (LAK) cells was conducted in 105 patients after
      noncurative resection of primary lung cancer. Half the patients received only the
      standard postoperative radiation therapy or chemotherapy (control group). The
      other half received immunotherapy with IL-2 and LAK cells in addition to the
      standard therapy (immunotherapy group). The primary endpoint was survival. The 7
      year survival rate was greater in the immunotherapy group than in the control
      group (39.1% vs. 12.7%, P < 0.01). Among patients with squamous cell carcinoma,
      there was no statistical difference in outcome. In contrast, the 7-year survival
      rate among patients with adenocarcinoma in the control group was only 5.2% but
      for those in the immunotherapy group it was 38.9% (P < 0.05). If resection was
      noncurative because of pulmonary metastasis, residual cancer or incomplete
      resection of lymph nodes, then immunotherapy was effective. If resection was
      noncurative because of residual cancer in the chest wall or diaphragm, or because
      of carcinomatous pleuritis or pleural dissemination, then there was no
      statistical difference in survival between the control group and the
      immunotherapy group.

PMID- 8528639
TI  - Surgical treatment of small cell carcinoma of the lung: advantage of preoperative
      chemotherapy.
AB  - To assess the effect of chemotherapy on postoperative survival of patients with
      small cell lung carcinoma (SCLC), 46 patients who underwent surgery at Kyoto
      University between 1976 and 1991 were retrospectively reviewed. Seventeen
      patients (37.0%) received chemotherapy prior to as well as after surgery
      (neoadjuvant therapy group), 23 (50.5%) received chemotherapy only after surgery
      (adjuvant therapy group), and the other six received no chemotherapy (non
      chemotherapy group). The 5-year survival rate of patients with c-Stage I or II
      disease in the neoadjuvant therapy group was as high as 80.0%, which seemed to be
      higher, although with no statistical significance, than that in the adjuvant
      therapy group (37.7%, P = 0.10). The 5-year survival rate of patients with c
      Stage III (IIIa or IIIb) disease in the neoadjuvant therapy group, although not
      satisfactory (10.0%), was significantly higher than that in the adjuvant therapy
      group (0.0%, P = 0.04). No patients in the non-chemotherapy group had survived 5
      years. Moreover, multivariate analysis showed that failure to employ preoperative
      chemotherapy was the strongest prognostic factor causing a poor prognosis (P =
      0.01). On the other hand, eight (30.8%) out of 26 patients with c-Stage I or II
      disease postoperatively proved to have mediastinal lymph node involvement (pN2
      3), and two (7.7%) proved to have intrapulmonary metastasis (PM). Considering the
      advantage of preoperative chemotherapy and the discrepancy between c- and p
      stage, sufficient chemotherapy prior to surgery should be employed, and may
      realize a good prognosis in patients with c-Stage I or II disease. In contrast,
      patients with c-Stage III disease are not appropriate as candidates for surgery
      even if preoperative chemotherapy is performed.

PMID- 8528640
TI  - Non-uniform dose/time fractionated radiation therapy and chemotherapy for non
      small cell lung cancer.
AB  - PURPOSE: A Non-uniform Fractionation schedule of large priming doses combined
      with concurrent chemotherapy and protracted RT was undertaken for the treatment
      of NSCLC. With several 5-year survivors, this study is reviewed with regard to
      local control, toxicity, and survival of patients. METHODS AND MATERIALS: Forty
      two patients with unresectable NSCLC were treated prospectively with initial
      priming doses followed by large field irradiation to the tumor and regional nodes
      to 3500 cGy. Patients were given a 1-week break and the treatment was repeated. A
      total dose of 7000 cGy was delivered over 9 weeks. Thirteen patients (Group A)
      were treated with RT alone. Twenty-nine patients (Group B) received concurrent
      chemotherapy; Cisplatin, 100 mg/m2, and 5-FU, 1 g/m2 for 24 h times 5 days.
      Sixteen patients also received Vinblastine, 3 mg/m2 on a weekly schedule. All
      patients have been followed more than 5 years. RESULTS: Overall complete response
      rate was 36% and partial response rate was 57%. Absolute survival at 2 years was
      26% and at 5 years was 14%. Local failure occurred in 28/42 (67%) patients. Late
      complications included pulmonary fibrosis (3), and osteochondritis (2).
      CONCLUSION: This approach of high-dose Non-uniform fractionated radiation therapy
      has yielded an absolute 5-year survival of 14%, which appears better than the
      long-term results often seen in treatment of NSCL cancer.

PMID- 8528641
TI  - Phase I-II and pharmacokinetic study of a new fotemustine schedule in advanced
      non-small cell lung cancer.
AB  - Fotemustine, a new nitrosourea derivative has already demonstrated activity in
      non-small cell lung cancer (NSCLC). In order to improve its therapeutic index, we
      designed a protocol in which Fotemustine was delivered with dose escalation on 3
      consecutive days as induction therapy followed by a 5-week rest period.
      Maintenance therapy consisted of 100 mg/m2 once every 3 weeks. Pharmacokinetic
      data were assessed during this Phase I-II study and reported here. PATIENTS AND
      METHODS: Nineteen patients with metastatic (17) or locally advanced (2) NSCLC
      were included in the present study. Ten of those with metastatic disease had
      brain metastases and 15 had previously received chemotherapy. Fotemustine was
      given at 50 mg/m2 on day 1-2-3 (group 1: four patients), 75 mg/m2 on day 1-2-3
      (group 2: 16 patients including two who had already received 50 mg/m2) and 100
      mg/m2 on day 1-2-3 (group 3: one patient). RESULTS: The maximal tolerated dose
      was 75 mg/m2 on day 1-2-3 (total cumulated dose 225 mg/m2). At this dose level,
      we observed 25% of Grade 3-4 neutropenia and 31% of Grade 3-4 thrombocytopenia.
      One patient died of pulmonary infection during aplasia. No other significant
      toxicity occurred. Of the 17 evaluable patients, one obtained a PR lasting 6
      months in group 2 and 1 PR lasting 3 months in group 3. No significant difference
      was noted in the AUC between days 1, 2 or 3 in any of the seven patients in whom
      a pharmacokinetic study of Fotemustine was performed. CONCLUSION: Administered on
      3 consecutive days, Fotemustine seems to be less effective and more toxic than
      other schedules tested in NSCLC. Despite the quality of the two responses
      observed, this protocol has been discontinued and the standard administration on
      days 1 and 8 remains the schedule of choice in NSCLC.

PMID- 8528642
TI  - Diabetic gastroparesis.

PMID- 8528643
TI  - Diabetic diarrhea.

PMID- 8528644
TI  - Systemic diseases causing disorders of defecation and continence.

PMID- 8528645
TI  - Gastrointestinal motility disorders in pregnancy.

PMID- 8528646
TI  - Endocrine-related gut dysfunction.

PMID- 8528647
TI  - Gastrointestinal manifestations of collagen-vascular diseases.

PMID- 8528648
TI  - Dioxins, furans and AHH-active PCB congeners in eggs of two gull species from the
      western Mediterranean.
AB  - Polychlorinated biphenyls, dibenzodioxins and dibenzofurans were analysed in eggs
      of a protected gull species, the Audouin's Gull (Larus audouinii) and compared to
      those of the Yellow-legged Gull (Larus cachinnans), both breeding in the Western
      Mediterranean (Ebro Delta and Medes Islands, respectively). Differences in
      concentrations as well as in congener profiles reflected differences in both
      habitat and diet of the two species. Levels of AHH-active PCB congeners were
      lower in Yellow-legged Gull (0.4-1.6 micrograms/g d.w) than in Audouin's Gull
      eggs (1.2-33.9 micrograms/g d.w.). These concentrations, expressed in
      international toxic equivalence factors (i-TEQ/g d.w.), were on average 24 times
      higher in the Audouin's gull. I-TEQ levels due to dioxins were also higher in
      this species by a factor of ca. 7. I-TEQ levels related to PCBs resulted 90-230
      times higher than those of dioxins and furans. Thus, AHH-inducing PCBs might
      represent even higher toxicological hazards than dioxins and furans to some
      populations of seabirds. The necessity of assessing the impact of these compounds
      in rare and protected species is pointed out.

PMID- 8528649
TI  - Levels of alpha-HCH, lindane, and enantiomeric ratios of alpha-HCH in marine
      mammals from the northern hemisphere.
AB  - The enantiomeric ratios of alpha-HCH were determined by chiral gas chromatography
      in blubber of marine mammals from regions of the northern hemisphere (North Sea,
      Baltic Sea, Arctic and Iceland). Cetaceans (harbour porpoises and white-beaked
      dolphins) showed a preferential accumulation of (+)-alpha-HCH. In blubber of
      harbour seals, grey seals and harp seals (+)-alpha-HCH was also more abundant
      than (-)-alpha-HCH. Hooded seals formed an exception with a (+/-) enantiomeric
      ratio of alpha-HCH < 1.

PMID- 8528650
TI  - Comparison of PCDD and PCDF concentrations after aerobic and anaerobic digestion
      of sewage sludge.
AB  - The anaerobic stabilization of raw sludges of different origin was investigated.
      Precursors like chlorophenol and chlorobenzene isomers were added to some of the
      samples. The change of the PCDD/F concentrations as well as the change in the
      pattern of the isomers and congeners was independent of the type and amount of
      the added precursor. With respect to the change of the PCDD/F concentrations the
      digestion properties were typical in each digestion series but not applicable to
      other digestion processes. The quality of the digestion was characterized by
      measuring the change of pH, controlling the biogas flow rate and the
      determination of the mineralization degree. The added chlorobenzenes and
      chlorophenols were almost completely degraded. The aerobic digestion occurred in
      ventilated batch reactors leading to a significant degradation of all PCDD/F
      homologues. The degradation ratio depends on the origin of the sewage sludge.
      Independent of origin individual congeners were partially or completely degraded.

PMID- 8528651
TI  - Pentachlorophenol accumulation in the freshwater mussels Anodonta anatina and
      Pseudanodonta complanata, and some physiological consequences of laboratory
      maintenance.
AB  - Freshwater mussels Anodanta anatina and Pseudanodonta complanata were exposed to
      (14C)-pentachlorophenol. The wet weight based bioconcentration factor (BCF =
      activity in animal per activity in water) at steady state varied from 80 to 120
      for A. anatina and from 61 to 85 for P. complanata. The species did not differ
      significantly in their wet weight or lipid based BCFs but dry weight based values
      were significantly higher (40-50%) for A. anatina. The soft tissue dry weight and
      dry weight based condition index of A. anatina (Cl4 = soft tissue dry weight per
      shell length) differed significantly between natural mussel populations. In
      animals kept from 4 to 8 months in laboratory conditions, the soft tissue dry
      weight and glycogen content decreased more rapidly when mussels were maintained
      at 15 than at 5 degrees C. However, glycogen content in the digestive gland or
      adductor muscle did not differ in mussels maintained in the laboratory (5 degrees
      C) when compared to the natural population. The adductor muscle protein content
      differed between laboratory maintained animals and the natural population in Lake
      Hoytianen but there was no difference in the soft tissue lipid content. Trace
      metal concentrations and calcium in the soft tissue were in general higher in
      laboratory maintained mussels. In addition, laboratory maintenance affected the
      reproductive cycle of A. anatina.

PMID- 8528652
TI  - Effects of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in human
      lymphoblastoid cells on aryl hydrocarbon hydroxylase activity.
AB  - The separate and concurrent effects of polychlorinated dibenzo-p-dioxin (PCDD)
      and dibenzofuran (PCDF) congeners on aryl hydrocarbon hydroxylase (AHH) activity
      in human lymphoblastoid cells were examined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin
      (2,3,7,8-tetraCDD) induced AHH activity about 9-fold acetone-treated AHH
      activity, while octachlorodibenzo-p-dioxin (octaCDD) did not affect the AHH
      activity and 2,4,6,8-tetrachlorodibenzofuran (2,4,6,8-tetraCDF) reduced the AHH
      activity by 34%. The concurrent effect of 2,3,7,8-tetraCDD with 1,3,6,8-tetraCDD
      on AHH inducibility was much smaller than expected. The concurrent effect of
      2,3,7,8-tetraCDD with 2,4,6,8-tetraCDF, octaCDD or 3,3',4,4',5,5'-hexaCB was as
      much as the effect of 2,3,7,8-tetraCDD alone. There was a difference between 3
      methylcholanthrene (MC) and 2,3,7,8-tetraCDD in the concurrent effects of 3
      methylsulfone-3',4,4',5-tetraCB (3-MSF-3',4,4',5-tetraCB) on AHH activity. The
      concurrent effect of MC with 3-MSF-3',4,4',5-tetraCB on AHH activity was equal to
      the effect of MC alone while that of 2,3,7,8-tetraCDD and 3-MSF-3',4,4',5-tetraCB
      on AHH activity was inhibitory. These results imply that congeners of PCDD and
      PCDF are considered to be more or less effective and isozymes of cytochrome P450,
      key enzymes for the AHH, induced by them are differently inhibited.

PMID- 8528653
TI  - Photodecomposition of 1,2,3,4- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      water-alcohol media on a solid support.
AB  - We used a hydrophobic solid support, octadecylsilylated silica gel (C18), packed
      in a quartz column as a reaction medium for the photolysis of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 1,2,3,4-tetrachlorodibenzo-p
      dioxin (1,2,3,4-TCDD). When we exposed the column to a 450 W UV lamp, the
      adsorbed 1,2,3,4-TCDD or 2,3,7,8-TCDD in 10% 2-propanol/water decomposed
      completely in 20 minutes and 5 minutes, respectively. The large estimated
      partition coefficient of 1,2,3,4-TCDD in 10% 2-propanol/water (> 1000) indicates
      that on the C18 stationary phase, both the saturated hydrocarbon chains and the
      absorbed 2-propanol may act as proton donors and accelerate the photolysis. In
      direct sunlight, the adsorbed 1,2,3,4-TCDD in 10% 2-propanol/water decomposed
      much faster than in a nonaqueous solvent (50% 2-propanol/methanol). This solvent
      effect is advantageous for the practical use of the C18 photolysis process in
      aqueous waste treatment. We have demonstrated that complete C18 trapping with
      continuous photodecomposition of TCDD contained in an aqueous alcohol waste is
      possible.

PMID- 8528654
TI  - CB pattern in the harbour porpoise: bioaccumulation, metabolism and evidence for
      cytochrome P450 IIB activity.
AB  - Metabolism of chlorobiphenyls (CBs) was studied in harbour porpoise by comparing
      patterns of CB-X/CB-153 ratios in blood, brain, liver and blubber with the
      patterns in herring, the main food source. The CBs were classified in five
      groups, based on the presence/absence of vicinal H-atoms (vic. Hs) in meta,para
      (m,p) and/or ortho,meta (o,m) positions and the number of ortho-Cl-atoms (ortho
      Cls). Plots of CB-X/CB-153 ratios in porpoise tissue vs the ratios in herring
      appeared to be linear for each CB group in all tissues. Slopes of these plots
      (metabolic slopes) were used as quantitative indicators of metabolic activity. In
      this way, activity of PB-type isozymes of the P450 monooxygenase system was
      apparent: in contrast to existing literature data, harbour porpoise appears to be
      able to metabolize congeners with m,p vic. Hs, even in the presence of more than
      2 ortho-Cls. The presence of 3-MC-type (MC-type) isozymes was also detected. The
      metabolic slopes were also used as basis for risk assessment. Due to their
      metabolism the most toxic non-ortho CBs were not present in the tissues at
      detectable levels. We suggest a risk assessment approach which takes this into
      account. It is considered to be an alternative and more reliable basis for risk
      assessment than the use of toxic equivalent factors. The results support the
      model of equilibrium distribution of CBs in harbour porpoise and the role of
      blood as central transport medium. The model has been developed for persistent
      compounds; it appears to hold for metabolizable CB congeners as well.

PMID- 8528655
TI  - The induction of micronuclei in mice hepatocytes and reticulocytes by
      tetrachloroethylene.
AB  - The clastogenicity of tetrachloroethylene (tetra) was detected by means of the
      micronucleus assay using hepatocytes and reticulocytes from ddY male mice, to
      understand its effects in upon hepatocellular carcinomas in mice. The frequency
      of micronucleated hepatocytes of mice that received a single injection of tetra
      after partial hepatectomy increased to levels that were significantly higher than
      those of controls treated with solvent. However, the micronucleus assay using
      peripheral blood reticulocytes from ddY male mice, revealed that tetra did not
      induce to a statistically significant increase in micronucleus frequency. These
      results suggested that tetra metabolites have a clastogenic effect in vivo upon
      mouse liver but not upon bone marrow cells.

PMID- 8528656
TI  - Is ECT the treatment of choice for first-break psychosis?

PMID- 8528657
TI  - ECT seizure duration: reliability of manual and computer-automated
      determinations.
AB  - Reliable monitoring of electroencephalographic (EEG) and electromyographic
      electroconvulsive therapy (ECT) seizure duration has become important as these
      assessments have become a routine part of the clinical practice of ECT. In this
      regard, accurate automated seizure duration determinations would be particularly
      valuable. As a result, the present study was performed to assess the reliability
      of available computer-automated determinations of seizure duration (Thymatron
      Model DGx ECT machine; Somatics, Inc.) and to explore the factors upon which such
      reliability as well as the determinations of experienced raters depend. We found
      that the experienced human raters had very high interrater reliability,
      significantly higher than either did with the automated Thymatron DGx ratings. In
      general, the reliability of all ratings declined in the context of artifact, poor
      postictal suppression, or an EEG seizure end point that was reached gradually.
      Reliability was also greater for continuation ECT as compared with the index
      course. The reliability of Thymatron DGx versus experienced human ratings was
      particularly sensitive to these factors, ranging from 0.68 when several of these
      factors were simultaneously present to 0.999 when all these factors were absent.

PMID- 8528658
TI  - Combined alfentanil-methohexital anesthesia in electroconvulsive therapy.
AB  - Eight patients receiving electroconvulsive therapy (ECT) were anesthetized with
      alfentanil, 25 mcg/kg, plus 20 mg methohexital, alternating with standard
      methohexital anesthesia. Combination alfentanil-methohexital anesthesia was
      associated with a 45% increase in EEG seizure duration. Preliminary evidence
      suggests that ECT anesthesia using short-acting opiate compounds may prove to be
      a promising alternative to standard modified ECT, especially for patients with
      brief seizures.

PMID- 8528659
TI  - Nursing aspects of electroconvulsive therapy.

PMID- 8528660
TI  - Electroconvulsive therapy: problems and prejudices.

PMID- 8528661
TI  - Survey of the practice of electroconvulsive therapy in North Carolina.
AB  - A survey of North Carolina hospitals was conducted to determine the distribution
      and characteristics of facilities that offer electroconvulsive therapy (ECT).
      Parameters examined in the survey included bed size, geographic location, and
      average volume of ECT treatments. Facilities that offer ECT make up only 14% of
      total hospitals surveyed. The majority of hospitals with ECT services are located
      in moderate to large urban areas. Specific areas of practice were surveyed for
      each facility, including type of ECT device, location of treatments/recovery,
      methods for monitoring ictal motor seizure, time required to perform treatments,
      staffing, and potential areas of ECT nursing education. Standard practices at
      facilities were found to be generally in compliance with American Psychiatric
      Association recommendations; differences in practices were identified. Potential
      nursing education topics related to ECT were ranked to determine those most
      useful to individual nursing staffs.

PMID- 8528662
TI  - Electroconvulsive therapy patient/family education.
AB  - Electroconvulsive therapy (ECT) is shrouded in myths and misconception. The
      notion of ECT often generates high levels of anxiety among patients and their
      families. In response to this anxiety a pre-ECT teaching intervention was
      implemented by nurses at Strong Memorial Hospital. This intervention encompasses
      a five-step plan designed to lessen anxiety and educate patients and families. In
      addition, it provides an opportunity for health care providers to become
      sensitive to the special needs and fears of individuals and families faced with
      the decision of whether or not to proceed with ECT as a treatment.

PMID- 8528663
TI  - Cognitive effects of electroconvulsive therapy: a clinical review for nurses.
AB  - Cognitive deficits are undesirable effects of electroconvulsive therapy (ECT).
      This article reviews the cognitive impairments associated with ECT, with an
      emphasis on linguistic information processing and memory dysfunction. Factors
      that may have an impact on the cognitive effects of ECT are discussed, along with
      recommendations for clinical interventions to aid in the treatment of these
      effects.

PMID- 8528664
TI  - Developing an outpatient electroconvulsive therapy program: a nursing
      perspective.
AB  - The increasing awareness that patients can be stabilized on maintenance
      electroconvulsive therapy (MECT) has led to the development of outpatient ECT
      programs. Just as ongoing dialysis treatments serve the renal patient, so do
      index and maintenance courses of ECT serve the patient with certain psychiatric
      illnesses. The planning and development of an outpatient ECT program is crucial.
      Nurses, physicians, and hospital administrators must carefully coordinate their
      efforts in order for the program to be viable. Such programs must be consumer
      oriented and place the patients and families first, in order to meet their needs
      and the demands of the many restrictions generated by health care reform.

PMID- 8528665
TI  - State of the art: nursing knowledge and electroconvulsive therapy.
AB  - Nursing services attempting to develop standards for their own facilities will
      find limited literature specific to nursing and electroconvulsive therapy (ECT)
      in American publications. From 1966 to December 1994, there were only 19
      publications in American nursing journals that provide a specific focus on
      nursing and ECT. Only one of these articles reported research findings. Twenty
      seven citations in Convulsive Therapy included nurse contributors. While the APA
      Task Force on the Practice of ECT has addressed educational needs of nursing and
      technical elements of the procedure, there do not currently exist specific
      standards for nursing practice in ECT. Concerns salient to nursing that have
      generated articles by nurses include instruction of patients, support to patients
      and families, safety of patients, assessment of clinical status, informed
      consent, and nurses' and patients' attitudes about ECT. Nurses are encouraged to
      join their physician-colleagues in developing and disseminating the information
      needed for the field of nursing to contribute its own expertise to the care of
      patients receiving ECT.

PMID- 8528666
TI  - Migraine after electroconvulsive therapy.
AB  - The first detailed case report of recurrent common migraine after
      electroconvulsive therapy (ECT) is presented; it involves a 52-year-old woman
      with major depressive disorder. The migraine symptoms corresponded to those of
      the infrequent spontaneous migraine attacks she had. After a change to propofol
      as the anesthetic because of methohexital intolerance, the migraine attacks
      ceased, apparently due to seizure generalization being inhibited by propofol. In
      patients with migraine, ECT may be expected to trigger a migraine attack,
      probably in the same way as spontaneous seizures. The possible reasons and
      significance are discussed.

PMID- 8528667
TI  - Electroconvulsive therapy for a schizophrenic patient in catatonic stupor with
      joint contracture.
AB  - The successful use of electroconvulsive therapy (ECT) for a patient in catatonic
      stupor with joint contracture is reported. A 53-year-old woman, who had been
      diagnosed with schizophrenia, developed a catatonic stupor unresponsive to
      neuroleptics. Physical emaciation gradually developed under food refusal and poor
      nutrition. Joint contracture of her extremities resulted from the long period of
      being bedridden in the same posture. In this case, modified ECT was dramatically
      effective for catatonic stupor without any complication despite the joint
      contracture.

PMID- 8528668
TI  - In response to letter by Dr. Fink.

PMID- 8528669
TI  - Yeast artificial chromosome cloning of the Xq13.3-q21.31 region and fine mapping
      of a deletion associated with choroideremia and nonspecific mental retardation.
AB  - Microscopically detectable deletions and X;autosome translocations have
      previously facilitated the construction of a high-resolution interval map of the
      Xq21 region. Here, we have generated three yeast artificial chromosome contigs
      spanning approximately 7 megabases of the Xq13.3-q21.31 region. In addition, a
      novel deletion associated with choroideremia and mental retardation was
      identified and mapped in detail. The proximal deletion endpoint was positioned
      between the loci DXS995 and DXS232, which enabled us to confirm the critical
      region for a locus involved in mental retardation. The distal deletion endpoint
      is situated in the Xq21.33 band, which allowed us to refine the order of several
      markers in this region.

PMID- 8528670
TI  - Presence of an IDS-related locus (IDS2) in Xq28 complicates the mutational
      analysis of Hunter syndrome.
AB  - A deficiency of the enzyme iduronate-2-sulfatase (IDS) is the cause of Hunter
      syndrome (mucopolysaccharidosis type II). Here, we report a study of the human
      IDS locus at Xq28. An unexpected finding was an IDS-related region (IDS2) which
      is located on the telomeric side of the IDS gene within 80 kb. We have identified
      sequences in this locus that are homologous to exons 2 and 3 as well as sequences
      homologous to introns 2, 3 and 7 of the IDS gene. The exon 3 sequences in the IDS
      gene and in the IDS2 locus showed 100% identity. The overall identities of the
      other identified regions were 96%. A locus for DXS466 was also found to be
      located close to IDS2. The existence of the IDS2 locus complicates the diagnosis
      of mutations in genomic DNA from patients with Hunter syndrome. However,
      information about the IDS2 locus makes it possible to analyze the IDS gene and
      the IDS2 locus separately after PCR amplification.

PMID- 8528672
TI  - A quality control study of CFTR mutation screening in 40 different European
      laboratories. The European Concerted Action on Cystic Fibrosis.
AB  - A quality control study was performed to determine the accuracy of cystic
      fibrosis (CF) transmembrane conductance regulator (CFTR) mutation screening in 40
      different genetic screening laboratories throughout Europe. A total of 9
      different samples were investigated blindly by the participating laboratories.
      Only 25/40 laboratories, i.e. 62.5%, were able to type all samples correctly for
      the mutations for which they routinely screened. Only 2 of the 9 samples were
      correctly typed in all 40 laboratories. The lowest accuracy rate was 80% for 1
      sample. 12.5% of the participating laboratories interpreted the F508C
      polymorphism as a true CF disease mutation and 23.5% interpreted the delta I507
      mutation as a delta F508 mutation. For the delta F508 mutation, a false-negative
      result of 3.75% was obtained. It is clear that the accuracy of CFTR typing should
      be improved.

PMID- 8528671
TI  - Linkage disequilibrium between the expanded (CAG)n repeat and an allele of the
      adjacent (CCG)n repeat in Huntington's disease patients of Greek origin.
AB  - Huntington's disease (HD) is associated with an expanded unstable (CAG)n repeat
      in the IT15 gene. This repeat was investigated in 44 HD patients and 59 of their
      relatives at risk who were members of 29 unrelated families from various parts of
      Greece. Abnormal elongation of the (CAG)n repeat ranging from 39 to 95
      trinucleotide units was found in all but one of the 44 HD patients tested with
      70% of these patients showing 42-47 repeats. The size of the expanded sequence
      correlated inversely with the age at disease onset (r = 0.77, p < 0.00001, n =
      43). In a single sporadic case, de novo expansion of the (CAG)n repeat was
      detected. Twenty-four of 59 asymptomatic family members at risk showed expansion
      of the (CAG)n repeat in the HD range (39-56 trinucleotide units) while three had
      intermediate alleles (36-37 repeats). Evaluation of the adjacent polymorphic
      (CCG)n repeat showed a strong linkage disequilibrium between the 7-unit (CCG)n
      repeat allele and the HD mutation, with 51% of normal and 93% of HD chromosomes
      showing this allele (chi 2 = 15.55, p < 0.0001, n - 260). These data on HD
      patients of Greek origin are consistent with the thesis that the (CAG)n expansion
      is the primary gene defect of the disease and that this mutation occurred
      primarily on chromosomes with the (CCG)7 repeat haplotype.

PMID- 8528673
TI  - Complete spectrum of PAH mutations in Tataria: presence of Slavic, Turkic and
      Scandinavian mutations.
AB  - Phenylketonuria (PKU) is an autosomal recessive disorder associated with a
      deficiency of hepatic phenylalanine hydroxylase (PAH). Although the molecular
      lesions present in the PAH genes of PKU patients have previously been determined
      in several Slavic populations, little is known regarding the molecular basis of
      PKU in the non-Slavic populations of the former Soviet Union. Guthrie card
      samples from twenty-one classical PKU patients residing in the Tatarian Republic
      were examined by a combination of denaturing gradient gel electrophoresis and
      direct sequence analysis. Twelve patients were of Tatarian ancestry, five were of
      Russian ancestry, and four were of mixed Tatarian and Russian ancestry. Two of
      the Tatarian patients were related, sharing one mutant allele. The single major
      allele identified in this study was R408W/RFLP haplotype 2/VNTR 3, which was
      present on 11/14 or 78.6% of all mutant chromosomes of Slavic origin, but on only
      10/27 or 37.0% of mutant chromosomes of Tatarian origin. This result suggests
      that this allele was introduced into central Asian populations during the
      eastward expansion of Slavs across the Eurasian landmass. A significant influence
      of Turkic peoples on Tatars can be inferred from the presence of R261Q.
      IVS10nt546g --> a, L48S, IVS2nt5g --> c and P281L, all of which are relatively
      common among Turks or have been observed in Mediterranean populations. Together,
      these alleles are present on 11/27 or 40.7% of all mutant chromosomes in ethnic
      Tatars. Surprisingly, the common Scandinavian mutation IVS12ntlg --> a was also
      present in Tataria, as was the delta agE221D222fs mutation found previously only
      in Denmark. Thus, some direct or indirect gene flow from Scandinavian into
      Tataria seems evident. Finally, the complete absence of PAH mutations previously
      observed in Oriental populations suggests that there was little gene flow into
      Tataria from Eastern Asia.

PMID- 8528674
TI  - Do Basque- and Caucasian-speaking populations share non-Indo-European ancestors?
AB  - Genetic evidence is consistent with the view that the Indo-European languages
      were propagated in Europe by the diffusion of early farmers. The existence of
      phylogenetic relationships between European populations speaking other languages
      has been proposed on linguistic and archaeological grounds, and is here tested by
      analyzing allele frequencies at ten polymorphic protein and blood group loci.
      Genetic distances between speakers of Basque and Caucasian languages are compared
      with those between controls, i.e. contiguous populations speaking Indo-European
      and Altaic. Although some statistical tests show an excess of genetic similarity
      between Basque and South Caucasian speakers, most results do not support their
      common origin. If the Basques and the Caucasian-speaking populations share common
      ancestors, recent evolutionary phenomena must have caused divergence between
      them, so that their gene frequencies do not appear more similar now than those of
      random pairs of populations separated by the same geographic distance.

PMID- 8528675
TI  - Can nucleated erythrocytes found in maternal venous blood be used in the
      noninvasive prenatal diagnosis of fetal chromosome abnormalities?
AB  - Nucleated erythrocytes found in the venous blood of pregnant women have been seen
      as the most promising type of cell for prenatal diagnosis of fetal abnormalities
      because of their short life span and their scarcity in the venous blood of
      healthy nonpregnant women. However, this review demonstrates that a great
      proportion of the nucleated erythrocytes found in venous blood during pregnancy
      are of maternal origin and that pregnancy per se induces nucleated erythrocytes
      of maternal origin to appear in the peripheral blood. More efficient and specific
      enrichment techniques are therefore needed to obtain purified nucleated
      erythrocytes of fetal origin in such quantities that reliable prenatal diagnoses
      can be performed.

PMID- 8528676
TI  - Immunotolerance: from new knowledge of mechanisms of self-tolerance to future
      perspectives for induction of renal transplant tolerance.

PMID- 8528677
TI  - Dopamine increases renal medullary blood flow without improving regional hypoxia.
AB  - The effects of dopamine (10 micrograms/kg/min i.v.) upon intrarenal
      microcirculation, total, superficial cortical and outer medullary blood flows and
      outer medullary pO2 were continuously determined in anesthetized rats with
      ultrasonic and laser-Doppler probes and oxygen microelectrodes. While total and
      cortical flows were unaffected, outer medullary flow increased by 35 +/- 5% (mean
      +/- SE, p < 0.01). Outer medullary pO2 was not significantly altered (from 16 +/-
      4 to 18 +/- 4 mm Hg). In volume-expanded rats total and cortical flows rose as
      well. In rats pretreated with indomethacin, with or without N omega-nitro-L
      arginine methyl ester HCl, dopamine restored renal microcirculation and
      ameliorated outer medullary hypoxia.

PMID- 8528678
TI  - Role of the extracellular matrix in the development of glomerulosclerosis in
      experimental chronic serum sickness.
AB  - Glomerulosclerosis is a severe complication of many immunologically mediated
      kidney diseases and is associated with a poor prognosis with respect to renal
      function. The aim of this study was to elucidate the role of the extracellular
      matrix (ECM) in the development of glomerulosclerosis in experimental immune
      complex glomerulonephritis. Induction of chronic serum sickness by repetitive
      injections of human IgG into preimmunized Wistar rats leads to the development of
      immune complex nephritis and glomerulosclerosis. At an early stage of the disease
      fibrinogen accumulation was observed along the endothelial cells, presumably
      related to damage of the endothelial lining. mRNA levels for several collagen
      types, laminin B1 and B2, and fibronectin were increased in both whole-kidney
      tissue and in isolated glomeruli, but morphological changes were not observed. In
      situ hybridization experiments demonstrated increased ECM mRNA levels in
      glomerular and tubular cells. Starting at week 15, glomerular mesangial matrix
      expansion and thickening of the glomerular basement membrane (GBM) was observed.
      ECM components were abundantly present. Coagulation factors were not observed at
      this point. ECM mRNA levels were decreased as compared to week 0, but were still
      above normal. Focal and segmental end-stage sclerotic lesions developed at weeks
      25-30, in which fibronectin and fibrinogen were the major constituents. Other ECM
      components were found peripherally from these lesions in the remnants of the
      mesangial matrix and GBM. Sclerotic matrices did not demonstrate an increase of
      cellular-fibronectin, and other constituents from the circulation were not
      present in the lesions. Glomerular ECM mRNA was decreased to normal levels.
      However, a dramatic increase of ECM mRNA expression was observed at sites of
      inflammatory infiltrate in the perivascular, interstitial, and periglomerular
      regions. In conclusion, the development of glomerulosclerosis in chronic serum
      sickness rats is preceded by mesangial matrix expansion in which several ECM
      components are increasingly expressed. Steady state mRNA levels for these
      components are increased before morphological changes are detectable. In the
      final stage there is a specific accumulation of exogenous fibronectin in the
      glomerular end-stage sclerotic lesions. Simultaneously, an interstitial
      inflammatory reaction takes place leading to increased ECM production in the
      tissue surrounding the damaged glomeruli.

PMID- 8528679
TI  - Differential effect of ischaemia-reperfusion injury on anti-oxidant enzyme
      activity in the rat kidney.
AB  - In the kidney, ischaemia-reperfusion results in both hypoxic and oxidant cellular
      injury which is most marked in the tubules of cortex and outer medulla. These
      contrasting conditions may have opposite effects on the expression of enzymes
      that reduce or repair oxidant damage. To investigate this, the activities of CuZn
      and Mn superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione
      S-transferase (GST) were measured after 4 h and 3, 6, and 10 days of reperfusion
      following sham surgery or 45- or 90-min left renal artery occlusion. The right
      kidney served as internal control. Sham surgery had no effect on Mn SOD or GPx,
      but caused small (p < 0.05) reductions in CuZn SOD and GST activities. Forty-five
      minutes of ischaemia had no net effect on Mn SOD, increased GPx activity (maximum
      at 6 days, p < 0.01), and reduced CuZn SOD (nadir 3 days, p < 0.02) and GST
      (nadir 6 days, p < 0.02) activities. Ninety minutes of ischaemia again had no net
      effect on Mn SOD, prevented the induction of GPx, and further suppressed the
      activities of CuZn SOD and GST. The activity of the non-anti-oxidant enzyme
      lactate dehydrogenase was equal in left and right kidneys after 45 min of
      ischaemia, but different (p < 0.01) 10 days following 90-min injury, due to a
      combination of reduced activity in the ischaemic kidney and an increase of
      activity in the internal control. The immediate effect of ischaemia-reperfusion
      injury on the kidney is to reduce the activity of intracellular anti-oxidant
      enzymes in proportion to the severity of the ischaemic insult. Recovery or net
      induction of enzyme activity paralleled tubular regeneration. Protection
      resulting in acquired resistance to a second ischaemic event is unlikely to be
      due to induction of anti-oxidant enzymes if it occurs within 6 days.

PMID- 8528680
TI  - Physiological and biochemical response of glomerular epithelial cells to
      exogenous epidermal growth factor.
AB  - Epidermal growth factor (EGF) is a growth-promoting cytokine which acts in a
      paracrine and autocrine fashion on epithelial cells of various tissues. Although
      previously demonstrated, we have now confirmed the presence of EGF receptors in
      cultured glomerular epithelial cells (GEC) using radioligand binding studies.
      Further, the biochemical consequences of EGF receptor activation in this cell
      type were investigated. In the presence of exogenous EGF, attachment of GEC to
      plastic was enhanced in a dose-dependent (0.62-10 ng/ml range) manner. At 10
      ng/ml of EGF, cell attachment was 5 times higher than in controls. After
      attachment, there was a 3-fold increase in cell proliferation rate in the
      presence of 10 ng/ml of EGF. Cells which multiplied and reached confluency in the
      presence of EGF were 80% larger in volume than in controls. In the presence of
      EGF, a 70% maximal increase in de novo protein synthetic activity as tested by 3H
      leucine incorporation was observed in the dose range of 0.62-10 ng/ml. Further, a
      dose-dependent increase in extracellular type IV collagenase (gelatinase) as well
      as in intracellular cathepsins B and D (150 and 260% of control, respectively)
      activities were noted. It is concluded that GEC respond to exogenous EGF by
      increasing their protein synthetic rate as well as their catabolic rate, thus
      resulting in enhanced turnover of macromolecules.

PMID- 8528681
TI  - Mesangial cell-matrix interactions: modulation of matrix expression in mesangial
      cells by extracellular matrices.
AB  - Aberrant extracellular matrices (ECMs) observed in mesangial areas during the
      progression of glomerulonephropathy could be produced by mesangial cells (MCs),
      interacting with altered ECM components, under the influence of various
      mediators. We studied the interaction between MCs and ECMs, especially focusing
      on matrix expression of MCs in contact with ECMs. We analyzed mRNA expression and
      protein synthesis of ECM components by cultured rat MCs which were plated on
      different types of ECMs, basement membrane-type matrix (BMM), type IV collagen
      and type I collagen. The level of mRNA for ECM components (alpha 1 type I
      collagen, alpha 1 type IV collagen, fibronectin and laminin B2) increased in MCs
      on the two types of collagen compared with BMM. The relative increase of alpha 1
      type I collagen mRNA expression in MCs on type I collagen was greater than that
      of alpha 1 type IV collagen expression. At the protein level, type I collagen
      production by MCs on coated type I collagen showed a 2.2-fold increase relative
      to that on BMM. MCs on type IV collagen produced it at an intermediate level. The
      phenomena were not associated with differences of proliferative activity, but
      were accompanied by minor morphological differences. These results indicate that
      ECMs can modulate the phenotype of MCs in terms of matrix expression and suggest
      that MC-matrix interaction may in part contribute to abnormal ECM accumulation in
      diseased glomeruli.

PMID- 8528682
TI  - Nitric oxide in IgA nephropathy patients with or without hypertension.
AB  - Nitric oxide (NO) is claimed to have a role in the pathogenesis of immune
      mediated glomerulonephritis and in the regulation of blood pressure (BP). NO
      rapidly converts to NO2-/NO3- which is excreted in the urine. We determined the
      daily NO2-/NO3- excretion in 26 IgA nephropathy (NP) patients and 20 healthy
      controls, recording the BP in each. There was no difference in NO2-/NO3-
      excretion between IgA NP patients and controls (999.1 +/- 66.8 vs. 1,051.2 +/-
      53.0 mumol/day). The urinary excretion of NO2-/NO3- in IgA NP patients whose mean
      diastolic BP remained above 85 mm Hg in spite of antihypertensive therapy, was
      significantly decreased (n = 8; 734.38 +/- 87.83 mumol/day; p < 0.05). There was
      a significant inverse correlation between mean diastolic BP and urinary NO2-/NO3-
      (p < 0.006). NO2-/NO3- excretion decreased with aging (p < 0.01) in IgA NP
      patients, but not in controls. The fact that there was no difference between the
      urinary NO2-/NO3- excretion of IgA NP patients and controls argues against the
      idea that NO production in immune-mediated IgA NP can be increased. The decrease
      of urinary NO2-/NO3- in hypertensive and in older IgA NP patients may be
      correlated with the impaired NO production of the endothelium.

PMID- 8528683
TI  - Environmental health hazards: how children are different from adults.
AB  - In policymaking on environmental health, it is often assumed that the entire
      population is exposed to and reacts to environmental contaminants in a similar
      manner. However, this assumption is misguided, especially where children are
      concerned. This article presents the scientific basis for the impacts of the
      environment on children, showing how children are different from adults in the
      ways in which they are exposed to environmental contamination and the ways in
      which they react to it when exposed. Specifically, the article examines the
      changing physical and biological environments of children. Children at different
      stages of development have unique physical risk factors for certain types of
      exposure because of changing location, levels of mobility, oxygen consumption,
      eating patterns, and behavior. When children are exposed to contaminants, their
      developing biological makeup--the way in which they absorb, distribute, and
      metabolize chemicals--will also affect how their bodies deal with the foreign
      substance. Each of these factors, along with the customs, laws, and regulations
      that affect the way in which children are exposed to the contaminants, had
      implications for the well-being of children in the years to come.

PMID- 8528685
TI  - School readiness.

PMID- 8528684
TI  - The Tennessee study of class size in the early school grades.
AB  - The Tennessee class size project is a three-phase study designed to determine the
      effect of smaller class size in the earliest grades on short-term and long-term
      pupil performance. The first phase of this project, termed Project STAR (for
      Student-Teacher Achievement Ratio), was begun in 1985, when Lamar Alexander was
      governor of Tennessee. Governor Alexander, who later served as secretary of
      education in the cabinet of President George Bush, had made education a top
      priority for his second term. The legislature and the educational community of
      Tennessee were mindful of a promising study of the benefits of small class size
      carried out in nearby Indiana, but were also aware of the costs associated with
      additional classrooms and teachers. Wishing to obtain data on the effectiveness
      of reduced class size before committing additional funds, the Tennessee
      legislature authorized this four-year study in which results obtained in
      kindergarten, first, second, and third grade classrooms of 13 to 17 pupils were
      compared with those obtained in classrooms of 22 to 25 pupils and in classrooms
      of this larger size where the teacher was assisted by a paid aide. Both
      standardized and curriculum-based tests were used to assess and compare the
      performance of some 6,500 pupils in about 330 classrooms at approximately 80
      schools in the areas of reading, mathematics, and basic study skills. After four
      years, it was clear that smaller classes did produce substantial improvement in
      early learning and cognitive studies and that the effect of small class size on
      the achievement of minority children was initially about double that observed for
      majority children, but in later years, it was about the same. The second phase of
      the project, called the Lasting Benefits Study, was begun in 1989 to determine
      whether these perceived benefits persisted. Observations made as a part of this
      phase confirmed that the children who were originally enrolled in smaller classes
      continued to perform better than their grade-mates (whose school experience had
      begun in larger classes) when they were returned to regular-sized classes in
      later grades. Under the third phase, Project Challenge, the 17 economically
      poorest school districts were given small classes in kindergarten, first, second,
      and third grades. These districts improved their end-of-year standing in rank
      among the 139 districts from well below average to above average in reading and
      mathematics.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8528686
TI  - Case studies of environmental risks to children.
AB  - Doing a better job of protecting children from environmental hazards requires
      having more and better information about both children's susceptibility and their
      exposure to toxic substances. There are many critical gaps in knowledge of this
      issue. This article presents several examples specifically related to children's
      exposure to pesticides which illustrate environmental risks for children. The
      cases examined include the risk posed to children by the use of the insecticide
      aldicarb on bananas, and reported illnesses in children caused by the use of the
      insecticide diazinon in the home and by the use of interior house paint
      containing mercury. The cases presented illustrate how regulatory agencies,
      parents, health care providers, and others who come into contact with children on
      a regular basis all have roles to play in filling in the information gaps
      regarding children's exposure to environmental hazards and the deleterious
      effects of these exposures.

PMID- 8528687
TI  - Environmental policy and children's health.
AB  - Understanding the differences in the effects of environmental contamination on
      children and adults is an important part of environmental policymaking; however,
      unless environmental health policies reflect the differences between adults and
      children, this knowledge will have little practical effect. The authors of this
      article consider how the unique vulnerabilities of children challenge
      environmental policymaking. First, they review the biological differences between
      children and adults, and then they critique the processes of risk assessment and
      risk management, the principal tools currently used to form federal environmental
      policy. While these tools are useful in developing environmental health policy,
      their implementation frequently fails to consider the unique vulnerabilities of
      children. In light of the potential to improve environmental policy for children,
      the authors review both the actual and prospective contributions of educational
      and advocacy efforts in changing the ways policy addresses children's
      environmental health, and discuss the interests of industries and the problems of
      environmental equity. Finally, they present a new approach to environmental
      health policymaking which places children, rather than individual toxicants and
      hazards, at the center of the risk assessment and management process.

PMID- 8528688
TI  - Effects of welfare reform on teenage parents and their children.
AB  - A key question in welfare policy concerns the potential that welfare-to-work
      programs have to develop in teenage parents the motivation and skills to provide
      financially for themselves and their children. The Teenage Parent Welfare
      Demonstration was a major experiment initiated in 1986 by the U.S. Department of
      Health and Human Services and evaluated by Mathematica Policy Research, Inc., to
      test the impact of a welfare-to-work program for teenage parents which
      anticipated many features of the federal Job Opportunities and Basic Skills
      training program later established in the Family Support Act of 1988. Teenage
      mothers entering the welfare system were randomly assigned to a regular services
      group or to an enhanced services group. Teen mothers in the enhanced services
      group faced mandatory school and work requirements enforced by financial
      sanctions and received support services such as case management, parenting
      workshops, child care assistance, and education and training opportunities. This
      article reviews the policy context in which the Teenage Parent Welfare
      Demonstration was designed and implemented, and describes how participation in
      the enhanced services group affected the teen mothers as adults and as parents.
      Results showed that, for the reasonable aggregate annual cost of $2,400 per
      participant, the program increased the 'teenagers' attendance at school and job
      training programs, and modestly increased the proportion who were employed to
      48%, compared with 43% among those receiving regular welfare services. As the
      participants' earnings from employment increased, their welfare grants shrank.
      Because these changes offset each other, the program did not improve the economic
      well-being of the families, although fewer tax dollars were needed to support
      them. The program did not discourage further childbearing, however, or affect
      either the parenting behavior of the young women or the development of their
      children, although the mothers who were most engaged in self-sufficiency
      activities were more positive and supportive when playing with their children.
      The Teenage Parent Welfare Demonstration experience revealed that the problems
      faced by teenage parents vary widely, making tailored services necessary. The
      evaluation results suggest that supportive, mandatory welfare-to-work
      interventions need not harm parents or their children in the short term, and that
      their modest positive effects on the financial independence of the teenage
      mothers may yield long-term rewards.

PMID- 8528690
TI  - Children's health and the environment.

PMID- 8528689
TI  - Immigrant children and their families: issues for research and policy. Board on
      Children and Families.
AB  - Discussions about immigration, focused on such policy issues as labor force
      participation and use of welfare programs, frequently fail to include
      considerations of children's well-being. Even those debates which center on
      programs that benefit children--such as schools, public assistance, and social
      welfare programs--are often based on issues related to short-term costs and
      societal impacts, neglecting considerations of the well-being and future
      contributions of immigrant children. Hence, immigrant children have been rendered
      largely invisible in policy spheres. Yet first- and second-generation immigrant
      children are the fastest-growing segment of the U.S. population under age 15. In
      this context, the Board on Children and Families of the National Research Council
      and the Institute of Medicine convened a workshop on immigrant children and
      families to review what is known about this population and to identify issues
      that warrant further examination. This article is based on the discussions at the
      workshop. Several themes emerged from the workshop, including the value of
      looking at immigrant children in the context of their families; the importance of
      understanding public concerns over the costs of immigrants, coupled with the
      difficulty of pinpointing just what those costs are; and the need for
      policymakers to address such policy issues as education and health care. The
      article concludes by identifying a number of areas in which research is warranted
      as immigrant children and families grow to become a core part of American
      communities, schools, and society.

PMID- 8528691
TI  - Outcomes for youths with serious emotional disturbance in secondary school and
      early adulthood.
AB  - Data from the National Longitudinal Transition Study of Special Education
      Students are used to describe the high school performance, social experiences,
      postsecondary education and labor market participation, and residential
      independence of students with serious emotional disturbance (SED) nationally.
      Young people with SED are found to fare poorly compared with youths with
      disabilities as a whole and with youths in the general population. The high
      school programs and adult services provided to young people with SED are then
      analyzed in a search for clues to contributors to the poor pattern of outcomes
      for such youths and to opportunities to improve those outcomes in the future.

PMID- 8528692
TI  - Adenosine modulates methylmercuric chloride (MeHgCl)-induced D-aspartate release
      from neonatal rat primary astrocyte cultures.
AB  - The effects of adenosine, and selective adenosine receptor agonists and
      antagonists on methylmercury (MeHg)-induced aspartate release were studied in
      neonatal rat primary astrocyte cultures. Whereas basal levels of D-[3H]aspartate
      release were unchanged upon treatment with adenosine or the selective A1 receptor
      agonists, N6-cyclopentyladenosine (CPA), cyclohexyladenosine (CHA), and R
      phenylisopropyladenosine (R-PIA), all partially reversed the MeHg-induced release
      of D-aspartate. Treatment of astrocytes with the xanthine derivative,
      theophylline, an adenosine antagonist, reversed the inhibitory effect of
      adenosine on MeHg-induced D-[3H]aspartate release. Since the effect of MeHg on D
      [3H]aspartate release is known to be associated with sulfhydryl (-SH) groups
      which are controlled by intracellular glutathione concentrations [GSH]i, we also
      evaluated the effects of adenosine, the A1 agonists CPA and CHP, and the
      adenosine antagonist, theophylline, on astrocytic [GSH]i. Attenuation of the
      stimulatory effect of MeHg on D-[3H]aspartate release by adenosine and its
      agonists occurred in the presence of reduced astrocytic [GSH]i, suggesting that
      other mechanisms must be invoked for this protective effect. Whilst the mechanism
      of MeHg-induced D-[3H]aspartate release is not known, the data suggest a role for
      adenosine in its regulation.

PMID- 8528693
TI  - Changes in neuronal activity related to the repetition and relative familiarity
      of visual stimuli in rhinal and adjacent cortex of the anaesthetised rat.
AB  - Employing the same techniques as have been used with conscious rats, this study
      describes neuronal responses signalling information concerning the prior
      occurrence of visual stimuli in unconscious rats. Recordings of the activity of
      387 neurons were made while anaesthetised rats were shown objects. Changes in
      neuronal responses related to stimulus repetition and the relative familiarity of
      visual stimuli were sought. The areas sampled were lateral occipital cortex, area
      TE of temporal cortex, perirhinal cortex and the hippocampal formation. The
      response to the first presentations of unfamiliar objects was significantly
      different from that to their second presentations for 30 (35%) of 86 visually
      responsive neurones; for 23 of the neurones the response was smaller when the
      stimulus was repeated, whereas for 7 it was larger. For all of these neurones the
      response change was maintained across intervening trials on which other stimuli
      were shown. For 4 (25%) of 16 neurones so tested, the response decrement
      persisted across at least 10 intervening trials. The activity of 63 neurones was
      recorded while rats were shown highly familiar as well as unfamiliar objects. The
      response to unfamiliar objects was significantly different from that to highly
      familiar objects for 3 (23%) of 13 visually responsive neurones. The types of
      neuronal response and their incidence expressed as a proportion of the number of
      visually responsive neurones were similar to those found in unanaesthetised rats
      (though the proportion of visually responsive neurones encountered in the
      anaesthetised rat was lower). The results indicate that information concerning
      the prior occurrence of stimuli is processed even under anaesthesia.

PMID- 8528694
TI  - Long-term glutamate desensitization in locus coeruleus neurons and its role in
      opiate withdrawal.
AB  - During opiate withdrawal, there is an elevated and prolonged efflux of glutamate
      and aspartate in the locus coeruleus (LC). The enhanced excitatory amino acid
      (EAA) release is thought to contribute to the withdrawal-induced activation of LC
      neurons and to the expression of the physical withdrawal syndrome. In this study,
      prolonged bath applications of glutamate to LC neurons in brain slices resulted
      in a slowly developing long-term glutamate desensitization (LTGD). LTGD was
      observed during extracellular recordings or in neurons voltage-clamped to -60mV,
      in both cases reaching a maximum of about a 50% reduction in the glutamate
      response. Responses in the desensitized cells gradually recovered within 3 h.
      Cyclothiazide, an inhibitor of rapid glutamate receptor desensitization did not
      prevent LTGD. LTGD could not be induced by prolonged applications of EAA agonists
      other than glutamate, either alone or in various combinations. However, after
      induction by glutamate, there was cross-desensitization to quisqualate but not to
      AMPA or NMDA. LTGD was blocked by either lowering extracellular Ca2+
      concentrations or by treatment with the protein kinase C inhibitor chelerythrine
      but not by inhibitors of calcium/calmodulin-dependent kinase or nitric oxide
      synthase. Applications of the protein kinase C activator phorbol diacetate did
      not cause a decrease in glutamate responses indicating that an activation of
      protein kinase C may not be sufficient for desensitization to occur. A decrement
      of the glutamate response resembling LTGD occurred after treatment by the protein
      phosphatase inhibitors okadaic acid or calyculin A. LC neurons in brain slices
      prepared from opiate-withdrawn rats exhibited glutamate responses that were
      initially desensitized and recovered within 3 h after withdrawal. These results
      suggest that LTGD in LC neurons may occur during opiate withdrawal and could
      contribute to the time course of LC hyperactivity and the associated behavioral
      withdrawal syndrome.

PMID- 8528695
TI  - Cyclic changes in the release of norepinephrine and dopamine in the medial basal
      hypothalamus: effects of aging.
AB  - Push-pull perfusion and HPLC were used to measure the release of norepinephrine
      (NE) and dopamine (DA) in the medial basal hypothalamus of young (4-5 months
      old), middle-aged (8-10 months old), and old (22-24 months old) rats. In the
      young animals, the afternoon of proestrus was characterized by a gradual increase
      in NE release and a simultaneous gradual decrease in DA release. The peak in NE
      release and the nadir in DA release occurred at about the time when the
      proestrous surges in serum LH and PRL are known to occur. No changes in NE and DA
      releases occurred in the afternoon of diestrus when serum LH and PRL are known to
      remain stable. In the middle-aged proestrous animals, the patterns of NE and DA
      releases were similar to those in the young proestrous animals, but the peak in
      NE release was attenuated and did not reach statistical significance. This
      corresponded with the reported attenuation in the LH surge in middle age. In the
      old persistently diestrous animals, NE and DA were released at constant rates,
      which correlated with the well-documented constant levels of serum LH and PRL in
      old age. These data provide an explanation for the simultaneous proestrous surges
      of LH and PRL and lead us to conclude that NE plays a facilitatory role in the LH
      surge, while DA, through its inhibitory action, regulates the PRL surge.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8528696
TI  - 5-HT1A, GABAB, and pirenzepine-insensitive muscarinic receptors are functionally
      coupled to distinct pools of the same kind of G proteins in rat hippocampus.
AB  - In order to probe the interaction between the neurotransmitter receptors and
      guanine nucleotide-binding regulatory (G) proteins in rat hippocampus, the high
      affinity GTPase activity stimulated by 5-hydroxytryptamine (5-HT), gamma
      aminobutyric acid (GABA), carbachol (CCh), and dopamine (DA) has been
      investigated, focusing on the additivity among the effects of these agonists at
      their maximally effective concentrations. There were simple additive
      relationships among 5-HT-, GABA-, and CCh-stimulated activities. As 5-HT, GABA-,
      and CCh-stimulated high-affinity GTPase activities are mediated by the 5-HT1A,
      GABAB, and pirenzepine-insensitive muscarinic receptors, respectively, the
      additive effects indicate that these three receptors are independently coupled to
      distinct pools of G proteins. In contrast, an apparent lack of additivity was
      seen between 5-HT- and DA-stimulated activities. This phenomenon was likely due
      to an activation of the common 5-HT1A receptor-mediated signalling by DA as well
      as 5-HT, since the DA-sensitive increment of the activity was potently inhibited
      by the 5-HT1 receptor antagonist methiothepin, but not by the DA D2 receptor
      antagonist raclopride.

PMID- 8528697
TI  - Substance P innervation of neurons projecting to the paraventricular hypothalamic
      nucleus in the rat nucleus tractus solitarius.
AB  - After injection of WGA-HRP-colloidal gold in the rat paraventricular nucleus
      (PVN), retrogradely labeled neurons were found mainly in the medial and
      commissural subnuclei of the nucleus tractus solitarius (NTS) around 0.5 mm
      caudal to the obex which is closely related to cardiovascular function. Electron
      microscopic immunohistochemistry in these areas demonstrated synaptic contacts
      between retrogradely labeled neurons and substance P-immunoreactive terminals.
      Innervation of NTS-PVN projection systems by substance P is suggested.

PMID- 8528698
TI  - Taxol stabilizes [Ca2+]i and protects hippocampal neurons against excitotoxicity.
AB  - Elevation of intracellular calcium levels [Ca2+]i induces microtubule
      depolymerization, a process which plays roles in regulation of cell motility and
      axonal transport. However, excessive Ca2+ influx, as occurs in neurons subjected
      to excitotoxic conditions, can kill neurons. We now provide evidence that the
      polymerization state of microtubules influences neuronal [Ca2+]i homeostasis and
      vulnerability to excitotoxicity. The microtubule-stabilizing agent taxol
      significantly attenuated glutamate neurotoxicity in cultured rat hippocampal
      neurons. Experiments in which [Ca2+]i was monitored using the Ca2+ indicator dye
      fura-2 showed that the elevation of [Ca2+]i induced by glutamate was
      significantly attenuated in neurons pretreated with taxol. Experiments using
      selective glutamate receptor agonists suggested that taxol suppressed Ca2+ influx
      through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors,
      but not through N-methyl-D-aspartate (NMDA) receptors. Taxol attenuated the
      neurotoxicity of the microtubule-depolymerizing agent colchicine; colchicine
      neurotoxicity was, in part, dependent on Ca2+ influx. These findings suggest that
      microtubules play a role in the mechanism of excitotoxicity and suggest that
      taxol and related compounds may be useful as antiexcitotoxic agents.

PMID- 8528699
TI  - Differential expression of vasopressin receptor binding in the hypothalamus
      during lactation in golden hamsters.
AB  - Vasopressin (AVP) receptor binding within hypothalamic sites was compared between
      cycling and lactating female golden hamsters. The density of AVP receptor binding
      was analyzed by quantitative autoradiography within the ventrolateral
      hypothalamus and dorsomedial hypothalamic nucleus. Lactation was correlated with
      a disappearance of AVP receptor binding within the ventrolateral hypothalamus. In
      contrast, lactation was associated with a two- to three-fold increase in the
      density of AVP receptor binding within the dorsomedial hypothalamic nucleus.
      These results suggest that AVP receptor binding within the ventrolateral
      hypothalamus is responsive to gonadal hormones in female golden hamsters.
      However, the increase in binding observed within the dorsomedial hypothalamus may
      be related to other neurobiological changes associated with lactation.

PMID- 8528700
TI  - Morphometric analysis of ventral mesencephalic neurons retrogradely labeled with
      Fluoro-Gold following injections in the shell, core and rostral pole of the rat
      nucleus accumbens.
AB  - Morphologically distinct subsets of mesotelencephalic neurons were sought
      following retrograde transport of Fluoro-Gold from iontophoretic injections
      relatively restricted to the medial shell, core or rostral pole subterritories of
      the nucleus accumbens. The diameter and lengths of Fluoro-Gold immunolabeled
      dendrites of medial shell-projecting neurons were less than those of core and
      rostral pole-projecting neurons.

PMID- 8528701
TI  - Antisense oligodeoxynucleotides to the kappa-1 receptor block the antinociceptive
      effects of delta 9-THC in the spinal cord.
AB  - Intrathecal pretreatment of mice with an antisense oligodeoxynucleotide directed
      against the kappa-1 receptor significantly reduced the antinociceptive effects of
      the kappa receptor agonist U50,488 as well as delta 9-THC, the major psychoactive
      ingredient found in cannabis. A mismatched oligodeoxynucleotide which contained
      four switched bases did not block the antinociception produced by U50,488 or
      delta 9-THC. Furthermore, kappa-1 antisense did not alter the antinociceptive
      effects of either the mu receptor-selective opioid DAMGO, or the delta receptor
      selective opioid DPDPE. By using kappa-1 antisense, we were able to demonstrate
      that an interaction occurs between the cannabinoids and opioids in the spinal
      cord.

PMID- 8528702
TI  - Early, but not late, antiepileptic treatment reduces relapse of sound-induced
      seizures in the post-ischemic rat.
AB  - Global ischemia was used to induce a sensitivity to sound-triggered generalized
      seizures in 24 male Long-Evans rats. All showed a generalized seizure when
      exposed to a 108 dB bell for 1 min. They were assigned randomly to 3 groups of 8,
      and received 30 additional sound exposures. The early treatment group was
      injected with valproate (200 mg/kg i.p) 1 h prior to each of the first 10 sound
      exposures. The late treatment group received the same treatment during the second
      set of 10 sound exposures after 10 sound exposures without treatment. The third
      group was untreated. Both early and late treated groups had a significant
      reduction in seizure incidence during the treatment period, i.e. both groups
      showed seizure control. However, in the late group seizures returned promptly
      when valproate treatment was discontinued, while the early group showed a
      sustained reduction in seizure susceptibility. Since this outcome corresponds to
      seizure remission, the findings of this study favor early treatment.

PMID- 8528703
TI  - An electrophysiological characterization of the projection from the central
      nucleus of the amygdala to the periaqueductal gray of the rat: the role of opioid
      receptors.
AB  - The midbrain periaqueductal gray (PAG) and the central nucleus of the amygdala
      (CNA) are both known to be involved in fear and anxiety, analgesia, vocalization,
      cardiovascular and respiratory changes, and freezing. Anatomical studies have
      shown that a connection between these two regions exists but little is known
      about the physiology or the neurochemical constituents of this pathway. The goals
      of this study were to characterize the projection from the CNA to the PAG using
      electrophysiological techniques and to determine whether mu- and/or delta-opioid
      receptors, which play a large role in a majority of the functions of the PAG, are
      involved in this pathway. Of the 38 PAG cells tested with single shock
      stimulation of the CNA, 44% responded; of those, 46% were excited and 54% were
      inhibited. The latency to onset of response for the inhibitory cells (12.71 +/-
      6.61 ms) was shorter than that of the excitatory cells (22.33 +/- 4.04 ms). Forty
      six percent of the 129 PAG cells tested with train electrical stimulation of the
      CNA responded; 44% were excited and 56% were inhibited. Chemical stimulation of
      the CNA (10 mM D,L-homocysteic acid) produced similar results; 48% (62/128) of
      PAG cells responded; 45% of cells were excited and 55% were inhibited. The
      baseline firing rate of the inhibitory cells was significantly higher compared to
      the excitatory cells. Chemical stimulation of the CNA produced an increase in
      blood pressure in 12 animals, a decrease in two animals, and had no effect on the
      blood pressure of 68 animals. The blood pressure changes ranged between 8.5 and
      26.3 mmHg with a mean of 16.2 +/- 2.2 mmHg. The effect of naloxone (given either
      on site in the PAG or systemically) on the response to CNA stimulation was tested
      in 21 cells. Twenty-five percent of the excitatory cells (2/8) and 77% (10/13) of
      the inhibitory cells were blocked by naloxone with the majority of the blocked
      cells located in the ventrolateral PAG. It is concluded that: (1) Approximately
      50% of cells in the lateral and ventrolateral columns of the PAG respond to CNA
      stimulation; (2) the inhibitory response is mediated by a faster conducting or a
      more direct pathway than the pathway that mediates the excitatory response; (3)
      neurons that are inhibited by CNA stimulation have a significantly higher
      baseline firing rate than neurons that are excited, suggesting that they may be
      tonically active interneurons; and (4) at least one link in the CNA-PAG pathway
      utilizes mu- or delta-opioid receptors.

PMID- 8528704
TI  - Intrauterine cocaine exposure of rabbits: persistent elevation of GABA
      immunoreactive neurons in anterior cingulate cortex but not visual cortex.
AB  - The effects of prenatal cocaine exposure on the development of the rabbit
      cerebral cortex were studied. Two cortical areas were compared: primary visual
      cortex (VC) and anterior cingulate cortex (ACC). ACC was selected because
      behavioral deficits observed in cocaine-exposed infants suggest the involvement
      of ACC. In addition, ACC receives dense dopaminergic innervation and cocaine's
      action in inhibiting the re-uptake of dopamine is believed to underly the
      rewarding properties of cocaine. VC was selected as a control area because there
      is no evidence of behavioral deficits associated with visual perception in
      cocaine-exposed infants, and because VC receives minimal dopaminergic
      innervation. Two aspects of cortical development were studied: (i) cortical
      morphology, growth and cytoarchitectonic organization; and (ii) the development
      of the GABAergic neurotransmitter system. Measures of postnatal cortical growth,
      including cortical lamination, cell number and soma size, were compared in
      cocaine-exposed or control (saline) rabbits aged P5-P60. There was no difference
      between cocaine and saline animals in any of these parameters, and cortical
      cytoarchitecture appeared normal. However, despite the absence of major
      abnormalities in cortical development, we found that the number of GABA
      immunoreactive neurons in cocaine-exposed animals was significantly higher than
      normal in ACC. This effect was highly consistent, was present in all laminae and
      at all ages studied, and persisted into maturity (P60). In contrast, in VC, the
      number of GABA-immunoreactive neurons in cocaine-exposed animals did not differ
      from normal. We suggest that increased GABA immunoreactivity may reflect a
      compensatory response to excessive excitatory input to ACC. A change in the
      balance of excitation and inhibition in ACC, reflecting 'noisy' or dysfunctional
      intracortical circuitry, may underly the emotional lability and attentional
      deficits characteristically described in infants exposed in utero to cocaine.

PMID- 8528705
TI  - The hypothalamic paraventricular nucleus in two types of Wistar rats with
      different stress responses. I. Morphometric comparison.
AB  - The present study evaluates the role of the hypothalamic paraventricular nucleus
      (PVH) in stress regulation by a morphometric comparison of the vascular, neuronal
      and synaptic properties of this nucleus in two lines of Wistar rats. It has been
      previously reported that these two lines of rats, indicated as APO-SUS
      (apomorphine-susceptible) and APO-UNSUS (apomorphine-unsusceptible) rats on the
      basis of their reactivity to a subcutaneous injection of apomorphine, display a
      variety of pharmacological and behavioral differences, including differences in
      their stress-coping mechanisms (Cools et al., Neuropsychobiology, 28 (1993) 100
      105). The results show a similar vascular and neuronal organization of the PVH in
      both lines, but distinct synaptic differences. The PVH (0.12 mm3 volume with
      about 15,000 neurons on one side) has an overall vascular density of 5.6%, with
      significant differences between subdivisions (parvocellular central part: 8.3%,
      parvocellular dorsal/ventral/posterior part: 4.6-5.3%), which means that
      vascularity is a useful tool to delineate subdivisions in the parvocellular PVH.
      The neuronal density of 132 x 10(3)/mm3 as found in the present study is two
      times higher than reported in a previous study Possible reasons for this
      discrepancy are extensively discussed. The most significant finding of the
      present study is the observation that APO-SUS rats have a significantly higher
      synaptic density (158 x 10(6)/mm3) in the PVH than APO-UNSUS rats (108 x
      10(6)/mm3). It is discussed in which way this synaptic difference may be
      correlated with the different activity of the hypothalamo-pituitary-adrenal axis
      in both lines of Wistar rats.

PMID- 8528706
TI  - The hypothalamic paraventricular nucleus in two types of Wistar rats with
      different stress responses. II. Differential Fos-expression.
AB  - The present study investigates the role of corticotropin-releasing hormone (CRH)
      neurons in stress regulation by a comparison of stress induced Fos
      immunoreactivity and CRH-immunoreactivity in the hypothalamic paraventricular
      nucleus (PVH) of APO-SUS (apomorphine-susceptible), APO-UNSUS (apomorphine
      unsusceptible), normal Wistar and adrenalectomized Wistar (ADX) rats. The first
      two types represent a good model to study the role of the PVH in stress
      regulation, since they show different stress responses and a differential
      synaptic organization of the PVH. After placement on an open field for 15 min all
      rats showed an increase in the number of Fos-immunoreactive nuclei compared to
      control handling. Interestingly, open field stress, but not control handling,
      induces significantly fewer Fos-immunoreactive nuclei in the PVH of APO-SUS rats
      (1255 +/- 49) compared to APO-UNSUS rats (1832 +/- 201). Experiments with ADX
      rats revealed that 93% of the CRH-immunoreactive neurons contained a Fos
      immunoreactive nucleus, which suggests that the differential Fos-expression in
      APO-SUS and APO-UNSUS rats represents a differential activation of the CRH
      neurons. This hypothesis is discussed in relation to reported differences in
      stress responses, stress-induced ACTH levels and synaptic organization of the
      PVH.

PMID- 8528707
TI  - Effects of gender on the central actions of neuropeptide Y and norepinephrine on
      vasopressin and blood pressure in the rat.
AB  - Neuropeptide Y (NPY) and norepinephrine are co-localized in the noradrenergic
      projection from the A1 nucleus of the medulla to the vasopressinergic
      magnocellular neurons of the supraoptic and paraventricular nuclei. Because this
      pathway is involved in the control of vasopressin release, we have examined the
      possibility that NPY and norepinephrine interact in this control. Because the
      stimulation of vasopressin release by the intracerebroventricular (i.c.v.)
      administration of norepinephrine is greater in male than in female rats, the
      experiments were carried out in conscious male rats and in female rats in the
      proestrous and non-proestrous phases of the estrous cycle. NPY (940 pmol i.c.v.)
      caused small sustained increases in plasma vasopressin concentrations that were
      greater in proestrous than in non-proestrous females and males. Norepinephrine
      i.c.v. increased plasma vasopressin levels transiently and to a greater extent in
      females than males. When NPY and norepinephrine were given together, the pattern
      of the vasopressin response was similar to that of norepinephrine alone. The
      magnitude of this response in males and proestrous females did not differ from
      that to norepinephrine alone; in non-proestrous females the response was twice
      that to norepinephrine alone. In non-proestrous rats, NPY also enhanced the
      pressor response to norepinephrine. Thus, NPY interacts centrally with
      norepinephrine in vasopressin release and cardiovascular function and this effect
      is dependent upon gender and phase of the estrous cycle.

PMID- 8528708
TI  - The effects of pregnenolone sulfate and ethylestrenol on retention of a passive
      avoidance task.
AB  - Two experiments using male rats evaluated the effects of a range of doses of the
      neurosteroid, pregnenolone sulfate (PS), or of the synthetic neurosteroid,
      ethylestrenol (E), on the retention of a passive avoidance task. The steroids
      either were given immediately after the training trial or 1 h before the first
      retention test. Retention tests were given both 24 h and 48 h after acquisition.
      In both experiments, separate groups of animals were trained under low or
      moderate footshock conditions. At all doses tested both PS and E improved
      retention under the low footshock conditions. In groups trained with the higher
      footshock, the steroid-treated groups performed no better than the vehicle
      controls. Indeed, there were suggestions that some doses impaired retention.
      These results seem best understood as an induction of bimodality or 'turbulence'
      in behavior as used in Chaos theory rather than a shift in an inverted U-shaped
      retention function. In the second experiment in which the steroids were given
      before retention testing, they were generally without effect.

PMID- 8528709
TI  - Long-term potentiation in vivo in the intact mouse hippocampus.
AB  - We describe the characteristics of long-term potentiation (LTP) in the intact
      mouse. Perforant path stimulation evokes both a population excitatory
      postsynaptic potential (pop-EPSP) and a population spike potential (pop-spike)
      from the hippocampal dentate gyrus in urethane anesthetized animals. LTP, as
      measured by increased pop-spike amplitude and pop-EPSP slope, was successfully
      induced and reliably maintained at a stable level for at least 12 h, the longest
      time tested. The LTP-inducing stimulus (3 trains of 400 Hz, 8 0.4 ms
      pulses/train) used in two strains of mice was less by half than that used in rat.
      These parameters for inducing LTP were also successfully applied to obtain LTP in
      two different transgenic mouse strains: one bearing a F1/Gap-43 promoter-lacZ
      fusion gene and another which overexpresses the S100 beta gene. We also examined
      the effects of protein synthesis inhibitors, cycloheximide (CXM) and anisomycin
      (ANI). When CXM or ANI was given 30 min before LTP induction, there was no
      persistent loss of LTP at the 4 h time point. However, if CXM was given 4 h
      before LTP induction, significant decay of the potentiated responses occurred 90
      min after induction. Half of the animals receiving CXM but not ANI showed a
      complete and sudden elimination of the entire response after the LTP-inducing
      stimulus. It was speculated that loss of a constitutively-expressed housekeeping
      protein, for example a calcium buffering protein, with an estimated half-life of
      2 h would lead to an inability to buffer LTP-induced alterations, such as
      intracellular calcium elevation, increasing intracellular calcium to toxic
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528710
TI  - Synaptic transmission and paired-pulse behaviour of CA1 pyramidal cells in
      hippocampal slices from a hibernator at low temperature: importance of ionic
      environment.
AB  - To investigate the effects of ionic changes possibly associated with hibernation,
      hippocampal slices prepared from golden hamsters were studied in artificial
      cerebrospinal fluid (ACSF) of variable composition (K+ 3-5 mM, Ca2+ 2-4 mM, Mg2+
      2-4 mM, pH 7.0-7.7) at temperatures of 15-20 degrees C, just above the
      temperature below which synaptic transmission is blocked. Population action
      potentials (population spikes, PSs) of CA1 pyramidal cells were evoked by
      stimulation of the Schaffer collaterals/commissural fibers with paired pulses
      (interpulse interval 50 ms, interval between pairs 30 s). The responses evoked at
      given temperatures were investigated as a function of extracellular ion
      concentrations. In ACSF containing 3 mM K+, 2 mM Ca2+ and 2 mM Mg2+, PSs could be
      evoked at temperatures of > approximately 16 degrees C whereas at lower
      temperatures synaptic transmission was blocked. The threshold temperature was
      slightly higher for the first (PS1) than for the second PS (PS2) evoked by paired
      pulse stimulation. The slices displayed paired-pulse facilitation (PPF) at all
      temperatures. Elevation of [K+]o from 3 to 5 mM depressed the amplitudes of both
      PS1 and PS2, with a stronger effect on PS2. PPF was reduced and, at near
      threshold temperatures, turned into paired-pulse depression (PPD). Elevation of
      [Ca2+]o from 2 to 4 mM increased the amplitude of PS1. The amplitude of PS2, in
      contrast, was reduced at near-threshold temperatures. PPF turned into PPD.
      Elevation of [Mg2+]o from 2 to 4 mM reduced the amplitudes of both PS1 and PS2,
      with a stronger effect on PS1. Accordingly, PPF was increased. Acidification by
      0.3 pH units strongly depressed the amplitudes of PS1 as well as PS2 and
      increased PPF. Alkalization by 0.4 pH units had only weak effects in the opposite
      direction. Changes in the ionic composition comparable to those investigated in
      the present study presumably occur in the brain interstitium of hamsters during
      entrance into hibernation. According to our results, such changes depress
      synaptic transmission at low temperatures in the hamster hippocampus in vitro.
      This modulation may be important for the regulation of neuronal activity during
      entrance into hibernation.

PMID- 8528711
TI  - Calbindin D-28k immunoreactivity in the rat accessory olfactory bulb.
AB  - The distribution pattern and the morphology of calbindin D-28k-immunoreactive
      neurons were studied in the accessory olfactory bulb of the rat using a
      monoclonal antibody and the avidin-biotin-immunoperoxidase method. Positive
      neurons were observed in all layers but the vomeronasal nerve layer. Scarce mono
      dendritic periglomerular neurons were calbindin D-28k-immunoreactive. Different
      morphological types of short-axon cells were calbindin D-28k-immunostained, with
      different degrees of intensity, in the boundary between the internal and external
      plexiform layer. In addition, deep short-axon cells located in the granule cell
      layer were calbindin D-28k-immunopositive. By contrast, previous studies
      described all cells in the rat accessory olfactory bulb as calbindin D-28k
      immunonegative. The staining pattern in the rat accessory olfactory bulb showed
      both similarities and differences with the distribution pattern of the same
      calcium-binding protein in the main olfactory bulb.

PMID- 8528712
TI  - What occupations have been associated with brain cancer, and, more specifically,
      what is the connection between brain cancer and electric utility work?

PMID- 8528713
TI  - Computation of odds ratios relative to a fixed nonexposed reference category:
      does it make a difference?

PMID- 8528714
TI  - Why are the occupational and smoking risks for bladder cancer not confounded? An
      epidemiologic puzzle.

PMID- 8528715
TI  - Hemoglobin adducts for in vivo dose monitoring and cancer risk estimation.
AB  - For the estimation of cancer risks from environmental chemicals, knowledge of the
      target dose is essential, dose being defined as the time integral of
      concentration in target tissues. In vivo doses from chronic or intermittent
      exposures are best determined from established steady-state levels of
      macromolecule adducts of reactive compounds or intermediates. For dose
      monitoring, hemoglobin (Hb) is preferred to DNA for several reasons:
      accessibility in large amounts, availability of methods for chemical
      identification, and well-determined life span due to absence of repair. For these
      reasons, and because of the proportionality of rates of DNA and Hb adduct
      formation, Hb adduct levels give better information on cumulative DNA adduct
      levels than do direct measurement of DNA adducts. The scientific background of Hb
      adduct measurement, target dose determination, and risk estimation based on the
      relative genotoxic potency, with gamma-radiation as reference standard, is
      reviewed and exemplified. The sensitivity of the method for Hb adduct measurement
      permits determination of exposures where the associated annual cancer risk is
      less than 1 per million. Besides application for studies of metabolism by
      determination of in vivo doses in exposed animals and humans, as a basis for risk
      estimation, Hb adduct measurement is used for hygienic surveillance of
      occupational exposures. Determination of Hb adducts by mass-spectrometric
      techniques gives a tool for identification of reactive metabolites, not only in
      individuals with known exposure, but also for characterization of adducts to Hb
      from compounds acting as mutagens (initiators) in the background carcinogenesis.
      This is the large fraction of the total number of cancer cases that occur among
      individuals without known exposure.

PMID- 8528716
TI  - ETS exposure in the workplace. Perceptions and reactions by employees in 114 work
      sites. Working Well Research Group [corrected].
AB  - Employees are often exposed to and bothered by environmental tobacco smoke (ETS)
      in the workplace; however, little is known about correlates of workers'
      perceptions of their exposure. In this study, 20,801 employees in 114 work sites
      in the United States were surveyed; variables related to perceptions of exposure
      and being bothered by ETS were entered into regression models. Many of the
      workplaces had total or partial restrictions on smoking in the workplace;
      however, over half of the respondents (52.4%) reported they were exposed to ETS
      at work. Smoking policy, smoking status, age, gender, living with a smoker, and
      occupation contributed to models for perceived exposure and being bothered by
      tobacco smoke. Work site smoking restrictions seem to have an impact on employee
      attitudes concerning exposure to ETS. About 35% of employees were bothered
      regularly by smokiness at their workplaces, which made their working conditions
      both uncomfortable and exposed them to an unsafe working environment.

PMID- 8528717
TI  - Monitoring acrylic fiber workers for liver toxicity and exposure to
      dimethylacetamide. 1. Assessing exposure to dimethylacetamide by air and
      biological monitoring.
AB  - Worker exposure to N,N-dimethylacetamide (DMAC) in an acrylic fiber manufacturing
      facility was measured, over a 1-year study period, by full-shift (12 hours)
      personal air monitoring for DMAC and by biological monitoring for levels of DMAC,
      N-methylacetamide (MMAC), and acetamide in spot urine samples. Ninety-three of
      127 male workers in seven job classifications in the solution preparation and
      spinning departments of the plant were monitored on the second consecutive
      workday after at least 3 days off for the first 10 months of the study and on
      both the first and second days during the study's final 2 months. Postshift
      urinary MMAC levels were significantly correlated (P < .0001, r2 = .54) with DMAC
      in air levels. An air level of 6.7 ppm 12-hour time-weighted average (TWA)
      corresponded to a urine MMAC level of 62 mg/g creatinine in a postshift spot
      urine sample obtained after the second consecutive workday. To minimize exposure
      misclassification due to variability in the regression relationship, a level of
      35 mg MMAC/g creatinine in a postshift spot urine sample was recommended as a
      biomonitoring index. Postshift urine MMAC levels did not appear to plateau at
      higher air levels, nor did it appear that the DMAC demethylation metabolic
      mechanisms became saturated at threshold limit value (TLV)-level air-exposure
      levels. Urine MMAC levels in postshift samples obtained the second workday
      appeared to be greater than levels in postshift first-day samples, but the number
      of days until this postshift level would plateau could not be determined from
      this study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528718
TI  - Monitoring acrylic fiber workers for liver toxicity and exposure to
      dimethylacetamide. 2. Serum clinical chemistry results of dimethylacetamide
      exposed workers.
AB  - Worker exposure to N,N-dimethylacetamide (DMAC) in an acrylic fiber manufacturing
      facility was measured, over a 1-year study period, by full-shift (12 hours)
      personal air monitoring for DMAC and biological monitoring for levels of DMAC, N
      methylacetamide (MMAC) and acetamide in post-shift spot urine samples. Evidence
      of liver toxicity was assessed by serum clinical chemistry tests (serum levels of
      total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline
      phosphatase, and gamma-glutamyl transpeptase) at least once during the study
      period for all 127 male workers in the two study departments and for 217 male in
      plant controls with no previous or current exposure to DMAC. If a worker's
      biomonitoring results exceeded one of two "trigger" values established for the
      study (60 mg MMAC/g creatinine or 136 mg DMAC equivalent/g creatinine),
      additional serum clinical chemistry tests were conducted at weekly intervals for
      3 weeks. DMAC-exposed workers were classified as either high exposure, if one or
      more biomonitoring result exceeded one of the trigger values, or unspecified
      exposure if none of them did. Control-group employees were classified as no
      exposure. Mean DMAC in air levels for the high- and unspecified-exposure groups
      appeared to differ (geometric mean DMAC in air levels of 1.9 and 1.3 ppm 12-hour
      time-weighted average, respectively). No significant DMAC exposure-related trends
      in hepatic serum clinical chemistry results were detected. Neither transient
      increases in serum analyte levels after a "high" biomonitoring result (one that
      exceeded a trigger value) nor an elevated mean level over the study period when
      compared with in-plant controls were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528719
TI  - Sensitivity and specificity of vibrometry for detection of carpal tunnel
      syndrome.
AB  - A cross-sectional study was performed to assess the utility of vibrotactile
      thresholds (VTs) obtained before and after a 10-minute period of wrist flexion as
      a method for detection of carpal tunnel syndrome (CTS) among adult subjects.
      Subjects with hand discomfort were recruited from patients referred to a
      university-based electromyography laboratory. Asymptomatic subjects were
      recruited from among office and technical staff at a professional school. In
      addition to electrophysiologic evaluation (EP), all subjects were offered VT
      measurement of the index and small fingers, bilaterally, before and after a 10
      minute period of wrist flexion. A total of 144 subjects were recruited, and three
      hand-condition groups were established: 57 hands had symptoms and EP results
      compatible with CTS (Group 1), 58 hands had symptoms compatible with CTS and
      normal EP results (Group 2), and 123 hands had no symptoms and normal EP results
      (Group 3). Group 1 was considered the "disease-positive" group, and Groups 2 and
      3 were both considered "disease-negative" groups. Analyses were performed
      separately for dominant and nondominant hands, and results were pooled when
      appropriate. Outcomes of interest were the VTs obtained from the index and small
      fingers before and after 10 minutes of maximal voluntary wrist flexion as well as
      variables calculated from them. Significant differences in mean VT were observed
      between the three hand-condition groups for most of the outcomes evaluated. At
      any given level of specificity, the sensitivity of vibrometry performed after 10
      minutes of wrist flexion was approximately two times that obtained before wrist
      flexion for detection of electrophysiologically confirmed CTS.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8528720
TI  - A new mask filter cartridge used to determine applicator inhalation exposure to
      an alachlor herbicide (Lasso) during normal spraying operations.
AB  - A filter cartridge with a low air-flow resistance was designed for use on a
      modified half-face respirator worn during the application of alachlor (Lasso)
      herbicide. The filter trapped large concentrations of alachlor while retaining
      the ability to trap small respirable droplets. Moreover, alachlor could be
      recovered from the disassembled cartridge and analyzed by conventional methods.
      The test cartridges were used in combination with conventional personal air
      samplers to determine whether the filters trapped more alachlor when compared
      with personal samplers and to determine accurately the amount of alachlor
      reaching the breathing zone. Farmers sprayed alachlor in the form of alachlor (N
      = 7) or alachlor mixed with other herbicides or surfactant (N = 15). An average
      of 4 x 10(-2) mg or 2 x 10(-4) mg/kg of applied alachlor reached the respirator
      filters. This concentration was 10-fold higher than the alachlor recovered from
      the personal samplers. The new filter cartridge is better for determining the
      amount of alachlor reaching the breathing zone, and there is a low potential for
      significant inhalation exposure to alachlor during normal spraying operations.

PMID- 8528721
TI  - Wrist squareness and median nerve impairment.
AB  - Previous research indicated that a wrist-squareness ratio (thickness/width)
      greater than .7 is likely to indicate a median nerve sensory latency greater than
      3.7 ms, usually a predictor of carpal tunnel syndrome (CTS). In this study, wrist
      thicknesses and widths were measured and wrist-squareness ratios were calculated
      for a sample of 417 railroad maintenance workers. Electrodiagnostic testing, in
      accordance with American Academy of Electrodiagnostics Medicine guidelines, was
      performed on both motor and sensory fibers of the median nerve to evaluate
      subjects for the presence of median nerve impairment typical of CTS. Results of
      this study indicate that wrist squareness is not a useful predictor of median
      nerve impairment typical of CTS in the railroad maintenance workers tested.

PMID- 8528722
TI  - Occupational risks for cutaneous melanoma among men in Sweden.
AB  - A population-based linked-registry was used to evaluate incidence of malignant
      melanoma of the skin among Swedish men by industry and occupation. There were
      3850 cutaneous melanoma cases identified in the 19-year follow-up of men employed
      in 1960. New associations were observed for men employed in the breweries and
      malt-processing industry and in shoe fabrication from leather and skins. Several
      findings supported associations previously reported in other countries, including
      an excess risk among workers in basic chemical production and the printing
      industry and among professional, technical, and white-collar workers. Risk
      overall was not increased among farmers, despite a significant excess of melanoma
      of the face, neck, and scalp. Although this linked registry analysis lacked
      information about specific agents, duration of employment, and occupational and
      recreational sun exposures, it did provide leads for new associations and
      confirmed previous ones. Nevertheless, because of these limitations, etiologic
      clues must be interpreted cautiously.

PMID- 8528723
TI  - Self-reported physical exposure and musculoskeletal symptoms of the forearm-hand
      among automobile assembly-line workers.
AB  - The aim was to study the prevalence of physical exposures and symptoms of the
      forearm-hand in a population with highly repetitive jobs. Automobile assembly
      line workers (ALWs) (n = 521) and a control group (CG) from the general
      population answered a questionnaire. Consistent differences were found between
      the groups. ALWs reported more symptoms from the forearm-hand and higher exposure
      to repetitive movements, precision movements, and manual handling (< or = 15 kg)
      than the CG. Female ALWs reported more symptoms and higher exposure to known risk
      factors for work-related forearm-hand disorders than their male colleagues. In
      conclusion, automobile assembly-line workers appear to be a high-risk group for
      work-related symptoms from the forearm-hand. Also, exposure to physical load
      should be conscientiously analyzed, since women may perform different tasks than
      men.

PMID- 8528724
TI  - Health risk appraisal in an occupational setting and its impact on exercise
      behavior.
AB  - The aim of this study was to evaluate the impact of a health risk appraisal (HRA)
      activity on exercise intention and behavior modification. In a mixed experimental
      and quasiexperimental design, three groups of subjects were formed: (1)
      preintervention, (2) postintervention, and (3) control. In the experimental
      design, the results showed that the employees in the postintervention group had,
      immediately after the HRA activity, an increased intention to exercise regularly
      compared with the employees in the preintervention group. According to the
      quasiexperimental design, the employees exposed to the HRA activity did not, 2
      months later, report regular exercise behavior that differed from that of the
      employees in the comparison group. It is suggested that an HRA activity should be
      supplemented with regular additional interventions over a given period of time to
      be successful in supporting the process of translating exercise intention into
      behavior.

PMID- 8528725
TI  - The psychosocial work environment of physicians. The impact of demands and
      resources on job dissatisfaction and psychiatric distress in a longitudinal study
      of Johns Hopkins Medical School graduates.
AB  - This study examines the relationship between the psychosocial work environment
      and cross-sectional job dissatisfaction and prospective psychiatric distress in a
      cohort of Hopkins Medical School graduates in midcareer. An instrument was
      constructed consisting of five scales: psychological job demands, patient
      demands, work control, physician resources, and coworker support. The results of
      scale reliability and factor analysis are presented. Higher job demands were
      found to be associated with increases in job dissatisfaction and psychiatric
      distress and greater resources were associated with decreased levels of
      dissatisfaction and distress. In multiple-regression analysis, only work control
      and social support were found to be independently associated with dissatisfaction
      and distress. These results suggest that the presence of control and social
      support at work protects physicians from developing job dissatisfaction and
      psychiatric distress.

PMID- 8528726
TI  - SIV infection of monkey spleen cells including follicular dendritic cells in
      different stages of disease.
AB  - Immunoaffinity enriched spleen follicular dendritic cells (FDCs), lymphocytes,
      and macrophages from SIVsm-inoculated cynomolgus monkeys (Macaca fascicularis) at
      different stages of disease were compared for latent and productive SIV
      infection. Analysis of FDCs by in situ hybridization, electron microscopy, and
      coculture assays indicated that comparatively high levels of virus were
      associated with the FDC fraction. Polymerase chain reaction (PCR) and RT-PCR
      results revealed that the levels for SIVpol DNA did not correlate with the level
      of env mRNA in the various cell subsets, suggesting differences in latency.
      Limiting dilution assays for spliced env mRNA showed a 10-100-fold higher amount
      of env mRNA in FDCs than in other spleen cell subsets early during SIV infection.
      At late stages of disease, the number of productively infected FDCs significantly
      decreased in parallel with a marked reduction of the FDC network and follicular
      involution. Our findings indicate that destruction of FDCs probably reflects a
      cytopathic effect of SIV and/or the activity of specific antiviral cytotoxic T
      lymphocytes.

PMID- 8528727
TI  - Characterization of an antigen shared by human thymic epithelium and human T cell
      leukemia virus p19 Gag protein.
AB  - The molecular basis for cross-reactive antibody binding to human T cell leukemia
      virus type I (HTLV-I) p19 core protein and human thymic epithelium has been
      defined with two monoclonal antibodies (mAbs), 12/1-2 and 13B12, raised to HTLV-I
      p19. The mAb 12/1-2 has previously been shown to react with HTLV-I p19, HTLV-II
      p22, and antigens of normal human thymic epithelium, placenta, and foreskin,
      whereas mAb 13B12 binds only to the carboxyl terminus of HTLV-I p19. In the
      present study, mAb 12/1-2 bound to a subset of Triton X-100-insoluble
      intermediate filaments in human thymic epithelium also recognized by antikeratin
      antibodies AE1 and AE3. The mAb 12/1-2 also reacted in Western blot assays with
      proteins of 54, 46, and 40 kDa present in extracts of human thymic epithelium and
      with hexameric peptides containing overlapping sequences of HTLV-I p19 with the
      amino acids IPP (amino acids 117-119). In contrast, the HTLV-I-specific mAb 13B12
      did not bind to human thymic epithelium and reacted with a single hexameric
      peptide containing the carboxy-terminal HTLV-I p19 sequence IPPPYV (amino acids
      117-122). Binding of mAb 12/1-2 to thymic epithelium could be inhibited by
      adsorption with peptide SP-79 containing a C-terminal sequence (amino acids 112
      125) of p19. The crossreactive IPP site is within a region of p19 that has been
      previously shown to be highly immunogenic in HTLV-I-infected individuals and that
      is also encoded by genes or mRNA of human cytokeratin 17, keratin 4, epidermal
      cytokeratin 2, and 50-kDa type I epidermal keratin. Thus, our studies define the
      sequence of a cross-reactive antigen on HTLV-I p19 that is also associated with
      keratin intermediate filaments from human thymic epithelium and other normal
      human tissues and that could serve as a focus of an autoimmune response during
      HTLV-I infection.

PMID- 8528728
TI  - Low HTLV-I/II seroprevalence in pregnant women in Congo and a geographic cluster
      of an HTLV-like indeterminate western blot pattern.

PMID- 8528729
TI  - Recombinant human immunodeficiency virus type 1 reverse transcriptase is
      heterogeneous.
AB  - Recombinant wild type (wt) and T215Y HIV-1 reverse transcriptase (RT) were
      isolated using three methods designated A, B, and C. The three samples of wt RT
      were kinetically indistinguishable with respect to dTTP turnover on
      poly(rA).p(dT)10. However, whereas the kinetic constants for dTTP and AZTTP for
      both T215Y B and T215Y C were similar to those of wt protein, T215Y A exhibited a
      twofold increase in Km value for dTTP and a 13-fold increase in Ki value for
      AZTTP with respect to wt protein purified in the same manner. We further
      investigated this observation by studying the denaturation of wt RT by urea. The
      urea denaturation curves monitored by fluorescence and circular dichroism
      spectroscopy were not coincident with the denaturation curve monitored by enzyme
      activity and yielded Cm values (the concentration of urea at which 50% of the
      protein is denatured) of 4.1 and 2.0 M urea, respectively. The noncoincidence of
      the transition curves reflects two separable, sequential, noncooperative
      conformational changes in the molecule: (a) from a catalytically active to an
      inactive conformation, and (b) from a catalytically inactive to a denatured,
      unfolded conformation. We therefore used denaturation as detected by changes in
      enzyme activity to compare the conformational stability of the three samples of
      wt and T215Y RT A, B, and C. The Cm values for T215Y RT did not differ from those
      of the respective wt; however, differences in Cm values were noted depending on
      how the protein was isolated. This suggested that the heterogeneity of the
      recombinant RT was due to small differences in conformation at or near the active
      site.

PMID- 8528730
TI  - Human antibody variable region gene usage in HIV-1 infection.
AB  - Human antibody variable region gene usage during human immunodeficiency virus
      type 1 (HIV-1) infection is examined in the following review, and several
      hypotheses are presented to account for the distinct patterns of antibody gene
      expression associated with infection. Evidence supporting qualitatively biased
      antibody gene expression has been derived from analysis of the human humoral
      immune response by isoelectric focusing (IEF) and serological and molecular
      studies of immunoglobulin (Ig) from different lymphoid compartments of HIV-1
      infected patients. Preferential usage of heavy-chain variable region (VH) gene
      families 1 and 4 is supported by serological studies of serum Ig and molecular
      characterization of anti-HIV-1 human monoclonal antibodies derived from infected
      patients. Negative biases against VH3 family gene usage are detected by
      polymerase chain reaction (PCR) studies of peripheral blood lymphocytes from AIDS
      patients but not by combinatorial phage display library techniques. Biased
      antibody gene usage and expression during HIV-1 infection may be related to HIV-1
      pathogenesis by limiting the available HIV-1 neutralizing repertoire. Further
      molecular characterization of anti-HIV-1 antibodies and in vivo expression of V
      region genes during HIV-1 infection should provide important information
      regarding antibody gene expression and its relationship to HIV-1 pathogenesis.

PMID- 8528731
TI  - Epidemiology of AIDS dementia complex in Europe. AIDS in Europe Study Group.
AB  - The aim of the study was to describe the epidemiology of AIDS dementia complex
      (ADC) in Europe and to assess the possible role of zidovudine therapy in
      preventing or delaying its occurrence. We used an inception cohort, with data
      collected retrospectively from patients' clinical records from 52 clinical
      centers in 17 countries across Europe. The subjects were 6,548 adult people with
      AIDS consecutively diagnosed from 1979 to 1989. The main outcome measures were
      codiagnosis of ADC at the time of AIDS diagnosis and ADC-free time after AIDS
      diagnosis. ADC was reported in 295 patients (4.5%) at the time of AIDS diagnosis
      and during follow-up in a further 402 of the 5,160 patients (7.8%) who were
      diagnosed with AIDS based on diseases other than ADC. Whether at the time of AIDS
      diagnosis or later, the occurrence of ADC was significantly associated with age,
      transmission category, and CD4+ cell counts. The risk was greater in older
      patients (14 and 19% greater, at AIDS diagnosis and after, respectively, for a 5
      year difference in age), in i.v. drug users than in homosexual and bisexual men
      (89 and 60% greater, at AIDS diagnosis and after, respectively), and for people
      with lower CD4+ cell counts (14 and 30% greater for a reduction of 1 on the
      natural log scale). Risk was almost double for women than for men. A significant
      reduction, of approximately 40%, was found in the risk of developing ADC after
      AIDS diagnosis for patients receiving zidovudine therapy, but this effect was
      present only during the first 18 months of treatment, irrespective of whether
      treatment began before or after AIDS diagnosis. In conclusion, an increase in the
      risk of developing ADC either at the time of AIDS diagnosis or thereafter is
      associated with increasing age, i.v. drug use, and decreased CD4+ cell count.
      Women tend to have a higher risk of ADC at the time of AIDS diagnosis. Zidovudine
      therapy appears to have a definite, but time-limited, effect of protecting
      patients against ADC development after AIDS diagnosis.

PMID- 8528732
TI  - Zidovudine side effects as reported by black, Hispanic, and white/non-Hispanic
      patients with early HIV disease: combined analysis of two multicenter placebo
      controlled trials.
AB  - The objective of this study was to determine whether HIV patients' subjective
      tolerance of zidovudine differs by racial or ethnic grouping by conducting a post
      hoc analysis of reported symptoms in two multicenter, placebo-controlled trials
      of zidovudine monotherapy for early HIV disease. Ratios of rates of developing
      new or worsening symptoms as reported by patients assigned to active drug or
      placebo were compared in groups of white/non-Hispanic, black, or Hispanic origin.
      Patients were included in the study if they had asymptomatic HIV disease and
      entry absolute CD4 lymphocyte counts below 500 cells/microL and were enrolled in
      National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group
      (ACTG) protocol 019 or had mild symptoms of HIV disease, were enrolled in ACTG
      protocol 016, met protocol eligibility criteria for the respective trial, and
      were categorized at entry as white/non-Hispanic (N = 1801), black (N = 195), or
      Hispanic (n = 214). The primary outcome measure was development of a new or
      worsening symptom of any severity. Among patients treated with zidovudine
      compared with placebo, the estimated risk for developing a new or worsening
      symptom was not significantly greater for blacks or Hispanics than for white/non
      Hispanics for any of the most frequently reported symptoms (p > 0.05 after
      adjustment for the multiple comparisons performed). Our analysis of 195 black and
      214 Hispanic patients did not reveal a significantly increased risk of subjective
      zidovudine intolerance compared with white/non-Hispanic subjects. If there is an
      increased risk of such intolerance in minority groups compared with white/non
      Hispanics, it is not likely to be clinically important.

PMID- 8528733
TI  - Mycobacterial infection in Mexican AIDS patients.
AB  - To describe the characteristics of mycobacterial infection in Mexico, we reviewed
      records from patients who were seen at the AIDS Clinic of the National Institute
      of Nutrition in Mexico City from 1983 to 1992. Of 460 AIDS patients, 118 (25.6%)
      were found to have mycobacterial infections by positive Ziehl-Neelsen stain,
      culture, or both. Cultures were completed for 66 of the 118 stain-positive
      specimens. Mycobacterium tuberculosis was the most common species found (n = 13),
      followed by M. avium complex (n = 12); 21 infections were identified a
      nonspecific mycobacteria other than tuberculosis (MOTT) and 20 infections were
      from species other than tuberculosis. Susceptibility testing was performed in
      only two tuberculosis cases, with one strain showing multidrug resistance. We
      conclude that mycobacterial infection is common among our AIDS population, and
      MOTT may be at least as common as M. tuberculosis. Previous reports of the rarity
      of MOTT could be related to the lack of adequate diagnostic methods in developing
      countries.

PMID- 8528734
TI  - In vivo role of IL-6 on the viral load and on immunological abnormalities of HIV
      infected patients.
AB  - In vitro experiments have suggested that interleukin (IL)-6 may contribute to
      human immunodeficiency virus (HIV) burden and to immunological abnormalities in
      HIV-infected patients. We had the opportunity to directly address this question
      in vivo through the virological and immunological monitoring of HIV-infected
      patients treated with an anti-IL-6 monoclonal antibody (mAb) for a lymphoma (ANRS
      018 trial). Sixteen courses of anti-IL-6 mAb administration, performed in 11
      patients, were studied. All patients were at a late stage of HIV infection. The
      HIV load and the immunological status were determined at the initiation of each
      course and at its end, 21 days later. The mAb induced no significant change of
      HIV load, as evaluated by p24 antigenemia, plasma viremia, and quantification of
      circulating HIV RNA by reverse transcriptase-polymerase chain reaction and
      branched DNA techniques. The anti-IL-6 mAb also did not affect CD4+, CD8+, and
      CD19+ circulating cell counts, nor the serum concentrations of sIL-2R and of
      sCD8. In contrast, the mAb completely abrogated acute-phase reaction, as
      demonstrated by the normalization of C-reactive protein and fibrinogen
      circulating levels (p = 0.013 and p = 0.008, respectively). It increased serum
      albumin concentration. The latter effect was restricted to patients with a
      spontaneously low albuminemia (p = 0.01). It decreased B-lymphocyte
      hyperactivity, as reflected by decreased IgG and IgA serum levels (p = 0.008 and
      p < 0.001, respectively), and by a decreased production of IgG in vitro (p =
      0.017). In contrast, the IgM hyperproduction was not affected by the mAb.
      Therefore, increased IL-6 production in HIV-infected patients at a late stage of
      the infection may not stimulate HIV replication in vivo, but it may represent a
      key mechanism contributing to the metabolic and immunological dysbalance of the
      disease.

PMID- 8528735
TI  - Back-projection and sensitivity analysis of the HIV-AIDS epidemic in the
      Caribbean.
AB  - In this study we estimated past human immunodeficiency virus (HIV) incidence in
      19 nations in the primarily English-speaking Caribbean and projected the course
      of the epidemic to the year 1999. We compared the results obtained from several
      different models of HIV incidence and different assumed incubation distributions.
      Linear and nonlinear optimization methods were used to fit several models (power,
      logistic, spline, and step) to adult (age 15 years or older) AIDS incidence data
      derived from our existing surveillance system. All four models tested gave good
      fits to the data, with estimates of cumulative HIV incidence in 1993 ranging from
      16,504 to 21,732. An increase in the assumed median of the AIDS incubation
      distribution by one year increased the estimates of current cumulative adult HIV
      incidence by approximately 12%; these estimates varied by as much as 6% between
      models. An adjustment of the data for possible reporting delay increased the
      estimates by approximately 7% and for underreporting by 25%. Despite their
      sensitivity to underlying assumptions, back-projection estimates provide useful
      insights into the patterns of HIV and AIDS incidence. The models indicate that
      HIV and AIDS incidences in the English-speaking Caribbean have been rising
      steadily, with adult HIV prevalence in the general population still less than 1%.

PMID- 8528736
TI  - Survival of AIDS patients in the emerging epidemic in Bangkok, Thailand.
AB  - Survival from the time of AIDS diagnosis to death was determined retrospectively
      among Thai patients (> or = 13 years old) who attended a public tertiary care
      infectious disease hospital in a suburb of Bangkok, Thailand, from February 1987
      through February 1993. An AIDS diagnosis was based on the 1987 Centers for
      Disease Control (CDC) definition, except Penicillium marneffei infection was
      included as an AIDS-defining condition. Of 329 AIDS patients, 152 (46.2%) had
      died. The median age at diagnosis was 31.5 years (range, 18-74) 306 patients
      (93.0%) were males. Reported risk categories were heterosexual contact (55.2%),
      injecting drug use (IDU, 22.6%), male homosexual or bisexual contact (9.5%), and
      unidentified risk or other (12.7%). Median survival time (Kaplan-Meier) for all
      patients was 7.0 months; 1-year survival probability was 39.2% (95% confidence
      interval [CI] = 31.5-46.9%). Cox's proportional hazards model showed three
      factors associated with survival: age, reported risk category, and presenting
      diagnosis. Patients aged 26 to 35 years survived longer (median survival time,
      10.6 months; relative hazard [RH] = 0.61, 95% CI = 0.44-0.85, referent: others),
      as did patients in sexual risk categories (median survival time, 7.3 months; RH =
      0.59, 95% CI = 0.40-0.78, referent: IDU and other categories). A single
      presenting diagnosis of extrapulmonary tuberculosis was also associated with
      longer survival (median survival time, 19.9 months, RH = 0.55, 95% CI = 0.35
      0.86, referent: other diagnoses). AIDS patients in the early phase of the
      epidemic in Bangkok have much shorter survival times than patients in developed
      countries, in part perhaps because they are often diagnosed late in the course of
      HIV infection. Increased attention should be given to the early diagnosis and
      treatment of these patients.

PMID- 8528737
TI  - Epidemiology of AIDS among Hispanics in Chicago.
AB  - The purpose of this study was to describe the epidemiology of AIDS among
      Hispanics in Chicago. These data are needed to tailor prevention and treatment
      programs across diverse Hispanic ethnic subgroups. To pursue Hispanic origin for
      the 1,289 Hispanic persons diagnosed with AIDS in Chicago, death certificates for
      those cases contained in Chicago's AIDS Reporting System (ARS) file that were
      decreased were examined for information on national origin; the AIDS case
      reporting form was modified in January 1994 to collect data on Hispanic ethnic
      origin; care providers were contacted for further information; and medical
      records were investigated to determine Hispanic ethnic origin. Ethnic origins
      obtained from all sources are according to patient self-report. All reference to
      Hispanic ethnic subgroups in this study include U.S.-born and foreign-born
      Hispanics. Ethnic subgroup was identified for 989 Hispanic persons (77% of the
      1,289 Hispanic cases) in the ARS. Data collected indicate that for all races and
      across Hispanic ethnic subgroups, Puerto Ricans have had the highest annual AIDS
      case rate since 1987. The mode of transmission for Puerto Rican males is
      predominantly through injection drug use (IDU), whereas for Mexican males the
      predominant mode of transmission is through males having sex with other males
      (MSM). For all Hispanic females, heterosexual contact was the predominant mode of
      transmission, with the largest proportion being sex partners of IDUs. The
      descriptive epidemiology of AIDS across Hispanic ethnic subgroups in Chicago
      highlights the need to target specific interventions among Puerto Ricans. In
      particular, culturally sensitive interventions tailored for Puerto Rican IDUs and
      their sex partners are needed, as are interventions for all Hispanic females who
      are at increased risk for heterosexual transmission.

PMID- 8528738
TI  - Mode of delivery and gestational age influence perinatal HIV-1 transmission.
      Italian Register for HIV Infection in Children.
AB  - Some data suggest that cesarean section reduces mother-to-child HIV-1
      transmission. To assess the influence of mode of delivery and other maternal and
      infant factors on the rate of transmission, we analyzed the data of 1,624
      children prospectively followed from birth. Of these, at the last visit 1,033
      were > 18 months of age or would have been had they not died of HIV-related
      illness. Among the 975 first singleton children, 180 [18.5%; 95% confidence
      limits (CL), 16.1-20.9] acquired infection, as did 8 of 56 (14.3%; 95% CL, 5.1
      23.5) second-born children. Multivariate stepwise analysis showed that vaginal
      delivery and development of symptoms in the mother were significantly and
      independently associated with a higher transmission rate (vaginal delivery; odds
      ratio, 1.69; 95% CL, 1.14-2.5; symptoms: odds ratio, 1.61; 95% CL, 1.12-2.3). In
      contrast, a history of maternal drug use, birth weight, breast-feeding (only 37
      infants were breast-fed), and child's sex did not have a significant impact on
      viral transmission. The percentage of infected children was highest (30.7%) among
      very premature infants (< or = 32 weeks of gestation); this significant trend
      subsequently decreased to 11.9% at the week 42 (p < 0.001), suggesting a parallel
      reduction in peripartum transmission. The reduced rate of infection observed in
      infants born by cesarean section underlines the urgent need for randomized
      controlled trials to evaluate the protective role of surgical delivery in
      preventing perinatal HIV-1 transmission.

PMID- 8528739
TI  - Expression of CD69 after in vitro stimulation: a rapid method for quantitating
      impaired lymphocyte responses in HIV-infected individuals.
AB  - A flow cytometric assay based on expression of the activation antigen CD69 was
      developed to analyze immunological responses of T cells from human
      immunodeficiency virus (HIV)-infected (HIV+) or HIV-seronegative (HIV-) donors
      after in vitro simulation by antigens and polyclonal activators. The levels of
      CD69 on freshly-isolated or unstimulated, cultured CD3+, CD4+, or CD8+ peripheral
      blood lymphocyte (PBL) subsets were low and did not differ greatly between HIV+
      and HIV- donors. The frequencies of CD3+, CD4+, and CD8+ lymphocytes from HIV+
      donors that expressed CD69 after culture with antigenic or mitogenic stimuli were
      significantly lower than in HIV- donors. Comparison of CD69 expression with
      [3H]thymidine incorporation revealed that both assays could detect lymphocyte
      responses to antigenic or mitogenic stimuli. The CD3+ PBL from HIV+ or HIV-
      donors did not show increased CD69 expression after culture with soluble or cross
      linked recombinant envelope glycoprotein, gp120. The gp120, however,
      significantly inhibited CD69 expression in phytohemagglutinin-stimulated T cells
      in vitro and may also affect T-cell activation in vivo. These studies demonstrate
      the usefulness of this CD69 expression assay for the rapid assessment of defects
      in immune responses of phenotypically defined lymphocyte subsets in HIV+ patients
      and for testing the effects of agents that modulate immune activation.

PMID- 8528741
TI  - Importance of different CD44v6 expression in human gastric intestinal and diffuse
      type cancers for metastatic lymphogenic spreading.
AB  - In 42 human gastric adenocarcinomas of intestinal (n = 25) and diffuse types (n =
      17) the expression of CD44v6 splice variants was investigated
      immunohistochemically and compared with the pattern of lymphogenic tumor
      spreading. Distinct differences were observed between the two cancer types: 92%
      of intestinal-type tumors expressed CD44v6 as in the intestinal metaplasia in
      chronic atrophic gastritis, while v6 expression occurred in only 17% of diffuse
      type cancers. The analysis of RNA expression confirmed the immunohistochemical
      data. Intestinal-type cancers yielded a much more complex pattern of
      amplification products hybridizing to exon v6 than did normal mucosa, whereas
      diffuse-type tumors did not express exon v6. Also the pattern of lymphogenic
      spreading was quite different between the two cancer types: in diffuse-type
      tumors only a sinus carcinosis without CD44v6 expression was observed in a
      significantly higher number of lymph nodes than in intestinal-type cancers, which
      showed in particular infiltrative lymph node metastases always with CD44v6
      expression as in the primary tumors. When infiltrative lymph node invasion
      occurred in v6-negative diffuse-type cancers, v6 neoexpression was also
      demonstrable in the lymph node metastases. Additionally, the number of
      infiltrative lymphogenic metastases increased with more extensive v6 expression
      in primary gastric cancers of both types. These data suggest that the expression
      of CD44v6 isoform is important for the infiltrative spreading of tumor cells into
      lymph nodes. Additionally, the phenotypic similarities in v6 expression between
      intestinal metaplasia and intestinal-type cancers, but not of tumors of diffuse
      type, may support the Correa hypothesis.

PMID- 8528742
TI  - FMS hemizygosity in myeloid dysplasia and acute myeloid leukemia with chromosomal
      aberration del(5)(q) demonstrated by polymerase chain reaction.
AB  - Interstitial deletions of the long arm of chromosome 5 del(5)(q), are recurring
      aberrations in the myelodysplastic syndrome and acute myeloid leukemia. Several
      genes located in region (5)(q23-34) have been implicated as being of pathogenic
      importance. In this study seven samples of six patients with myelodysplastic
      syndrome and acute myeloid leukemia who have the del(5)(q) aberration were
      analyzed by polymerase chain reaction (PCR) and Southern blot technique. FMS
      hemizygosity was demonstrated in all patients. PCR analysis from peripheral blood
      samples confirmed the observations of this aberration found by semiquantitative
      Southern blot. PCR-based analysis can be used for primary diagnosis in addition
      to cytogenetic evaluation and for follow-up in patients with del(5)(q)
      aberration.

PMID- 8528744
TI  - Sense, antisense, nonsense: where's the right way?
AB  - The application of small nucleic acids is slowly moving from chemistry and
      molecular biology laboratories into the clinic. However, the development of a new
      family of therapeutics is always difficult. Research must be performed to produce
      chemically compatible compounds in vivo and pharmacological investigations are
      necessary to precisely define the in vivo mechanisms of action of these
      potentially new drugs. The "2nd International Conference on Antisense Nucleic
      Acids: Biology, Pharmacology, Therapy" held in Garmisch-Partenkirchen addressed
      these questions.

PMID- 8528740
TI  - Genetic background and environment contribute synergistically to the onset of
      autoimmune diseases.
AB  - Autoimmune diseases result from the breakdown of "self" tolerance. Environmental
      factors appear to be responsible for triggering this errant immune response,
      directed against self-tissue determinants, only when a susceptible genetic
      background is present in an individual. Autoimmune diseases, normally
      characterized by their association with certain HLA alleles, also share other
      features: the presence of autoantibodies, autoreactive T lymphocytes, and an
      intermittent clinical course of exacerbations and remissions. In cases of organ
      specific diseases, as well as in cases of multi-system autoimmune diseases,
      viruses are increasingly implicated as such environmental triggers. Current
      molecular biology techniques have permitted a fine dissection of the genetic
      background of susceptible individuals and have enabled a more complete
      characterization of the immunocompetent cells involved in this autoaggression.
      Molecular approaches will soon allow us to pinpoint the characteristics of the
      environmental stimuli, so that protective strategies could be formulated to spare
      susceptible individuals from their ill effects.

PMID- 8528743
TI  - Tumor-associated lymphocytes (TAL) are competent to produce higher levels of
      cytokines in neoplastic pleural and peritoneal effusions than those found in sera
      and are able to release into culture higher levels of IL-2 and IL-6 than those
      released by PBMC.
AB  - This work was designed to study the proliferative response of tumor-associated
      lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and
      the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of
      the same patients. We also compared the serum levels of the cytokines interleukin
      (IL) 1 beta, 2 and 6, tumor necrosis factor-alpha (TNF alpha) and soluble IL-2
      receptor (sIL-2R) with those present in neoplastic effusions of the same
      patients. Moreover, we examined the ability of TAL and peripheral blood
      mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to
      express membrane CD25 following their stimulation with phytohemagglutinin (PHA)
      in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25
      expression by PHA-stimulated PBMC of the patients with neoplastic effusions with
      a series of 90 cancer patients without neoplastic effusions and 20 normal healthy
      subjects. Thirteen neoplastic pleural and eight peritoneal effusions were
      collected from 11 patients with primary lung cancer, 7 with primary epithelial
      ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with
      pancreatic cancer. The proliferative response of TAL from neoplastic effusions
      against autologous tumor cells was lower than the response to PHA, IL-2, and anti
      CD3, but significant. The percentage distribution of CD3+ and CD8+ lymphocyte
      subpopulations was higher in peritoneal than in pleural effusions, while the
      CD16+ subset was higher in pleural than in peritoneal effusions. The percentage
      distribution of CD16+ was significantly lower in pleural effusions than in PBMC
      of patients with pleural effusions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528745
TI  - Clinical trials: specific problems associated with the use of a placebo-control
      group.
AB  - In order to test hypotheses prospectively with hard data and against placebo, the
      scientific method of clinical trials has been developed. The present paper
      focuses on specific problems associated with the use of a placebo control group.
      (a) The placebo highlights the ethical dilemma that a controlled clinical trial
      can place us in. (b) Also, in a trial an atmosphere is created of enhanced risks
      of placebo effects. (c) "Significantly different from placebo" does not
      necessarily mean clinically relevant. (d) A biased placebo period due to carry
      over effect is a common problem of controlled trials with a cross-over or self
      controlled design. (e) Likewise an asymmetric placebo group is also a common
      problem in parallel-group designs. (f) The response to a placebo is generally
      small in comparison with the response to active treatment and is therefore
      sometimes more susceptible to bias. It is emphasized that routinely accounting
      for such problems may further improve the powerful method of controlled clinical
      trials.

PMID- 8528748
TI  - Cryptocrine signaling in the thymus network and T cell education to
      neuroendocrine self-antigens.
AB  - Both during phylogeny and ontogeny the thymus appears as a nodal point between
      the two major systems of cell-to-cell signaling, the neuroendocrine and immune
      systems. This review presents the experimental observations which support a dual
      role in T cell selection played by the thymic repertoire of neuroendocrine
      polypeptide precursors. Through the mode of cryptocrine intercellular signaling
      thymic neuroendocrine-related precursors synthesized in thymic epithelial cells
      have been shown to influence the early steps in T cell differentiation. In
      addition, thymic neuroendocrine-related polypeptides are a source of self
      antigens which are presented by the major histocompatibility system of the thymic
      epithelium. Preliminary data also suggest that the intrathymic T cell education
      to neuroendocrine self-antigens is not strictly superimposible to the antigen
      presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF
      II) was identified as one dominant member of the insulin family expressed by
      thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF
      II derived self-antigens is under current investigation. If further confirmed,
      the central tolerogenic properties of IGF-II could be considered in the
      elaboration of a strategy for an efficient and safe prevention of insulin
      dependent diabetes.

PMID- 8528747
TI  - Looking beyond the dogma of genomic steroid action: insights and facts of the
      1990s.
AB  - The genomic theory of steroid action has been the unquestioned dogma for the
      explanation of steroid effects over the past four decades. Despite early
      observations on rapid steroid effects being clearly incompatible with this
      theory, only recently has nongenomic steroid action been more widely recognized
      and led to a critical reappraisal of unsolved questions about this dogma.
      Evidence for nongenomic steroid effects is now coming from all fields of steroid
      research, and mechanisms of agonist action are being studied with regard to the
      membrane receptors and second messengers involved. A prominent example of a
      receptor/effector cascade for nongenomic steroid effects has been described for
      rapid aldosterone effects in various cell types, including lymphocytes and
      vascular smooth muscle cells. Rapid in vitro effects of aldosterone on the sodium
      proton antiport have been found in human lymphocytes, cultured vascular smooth
      muscle, and endothelial cells involving non-classical membrane receptors with a
      high affinity for aldosterone, but not for cortisol, and phosphoinositide
      turnover. Another important second messenger, [Ca2+]i, is consistently increased
      by aldosterone within 1-2 min. In vascular smooth muscle cells, calcium is
      released from perinuclear stores while in endothelial cells a predominant
      increase of subplasmalemmal calcium is seen. Effects are half-maximal at
      physiological concentrations of free aldosterone (0.1 nM), while cortisol is
      inactive up to 0.1 microM; the classical mineralocorticoid antagonist canrenone
      is ineffective in blocking the action of aldosterone. The data show that
      intracellular signaling for nongenomic aldosterone effects also involves calcium,
      but pathways of cell activation may vary between different cell types. Further
      evidence for nongenomic steroid effects is encountered presently for various
      groups of steroids such as neurosteroids, mineralocorticoids, vitamin D3, and sex
      hormones. Future research will have to target the cloning of the first membrane
      receptor for steroids and evaluate the clinical relevance of these rapid steroid
      effects.

PMID- 8528749
TI  - Characterization of the 5'-flanking region and chromosomal assignment of the
      human brain natriuretic peptide gene.
AB  - Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in
      the ventricle, and synthesis and secretion of BNP are greatly augmented in
      patients with congestive heart failure and in animal models of ventricular
      hypertrophy. In order to elucidate the molecular mechanisms underlying the human
      BNP gene expression in the heart, the human BNP gene was isolated from a size
      selected genomic minilibrary. The 1.9-kb human BNP 5'-flanking region (-1813 to
      +110) contained an array of putative cis-acting regulatory elements. Various
      lengths of the cloned 5'-flanking sequences were linked upstream to the bacterial
      chloramphenicol acetyltransferase (CAT) gene, and their promoter activities were
      assayed. The 1.9-kb promoter region showed a high-level CAT activity in cultured
      neonatal rat ventricular cardiocytes. When the CT-rich sequences (-1288 to -1095)
      were deleted, the high-level activity was reduced to approximately 30%. The 399
      bp BNP 5'-flanking region (-289 to +110) showed approximately 10% activity of the
      1.9-kb region. Furthermore, using human-rodent somatic hybrid cell lines, the BNP
      gene was assigned to human chromosome 1, on which the atrial natriuretic peptide
      gene is localized. The present study leads to a better understanding of the
      molecular mechanisms for the human BNP gene expression in the heart.

PMID- 8528750
TI  - Complement C1q and C3 mRNA expression in the frontal cortex of Alzheimer's
      patients.
AB  - The levels and cellular localization of mRNA for complement C1q and C3 were
      examined by RNA gel blot and nonradioactive in situ hybridization in the frontal
      cortex of patients with Alzheimer's disease (AD) and age-matched controls. We
      found that the hybridization signal for C1q mRNA was markedly increased (approx.
      3.5-fold) in the frontal cortex of AD patients compared to that in age-matched
      controls. In contrast to previous reports we also found that the levels of C3
      mRNA, although well expressed, did not differ significantly between AD cases and
      age-matched controls. Nonradioactive in situ hybridization using digoxigenin
      labeled ribo-probes revealed that transcripts coding for both C1q and C3 were
      closely associated with neurons. These results support the hypothesis that
      complement could play a role in neuronal degeneration which has been observed in
      the brain of AD patients.

PMID- 8528746
TI  - CD44: physiological expression of distinct isoforms as evidence for organ
      specific metastasis formation.
AB  - Continuous progress has been achieved during recent decades in the therapy of
      metastasizing malignancies by improving chemotherapeutic strategies and new
      approaches in radiation therapy. Genetic manipulation of tumor cells and of the
      tumor fighting immune system is hoped to add significant contributions to
      curative interventions in disseminated tumors. That we are still far from
      eradicating death by malignant growth is due ultimately to our limited
      understanding of the cascade of events resulting in metastasis formation, which
      until recently was believed to rely on multiple rounds of mutation and selection
      processes. This implies an individually specific history of each metastatic
      tumor, which would rule out uniform diagnostic and therapeutic concepts. When it
      was noted in a rat tumor model that the transfer of cDNA of a single gene, a CD44
      variant isoform (CD44v) covering the exons v4-v7, sufficed to initiate metastasis
      formation of a locally growing tumor, hope was created that a "metastogene" may
      have been identified. Although the idea of CD44v expression as a unifying concept
      for tumor progression was not sustained, the discovery of CD44v-initiated
      metastatic spread allowed a conceptually new hypothesis on tumor progression as a
      consequence of the reactivation of genetic programs of ontogeny, stem cell
      differentiation, and/or lymphocyte activation. Since distinct CD44 isoforms play
      an important role in these processes, unraveling the functions of this family of
      molecules can indeed provide a cornerstone in the understanding of tumor
      progression. This article summarizes briefly the present knowledge on known
      functions of CD44 isoforms with particular focus on parallels between
      physiological programs and tumor progression.

PMID- 8528751
TI  - Interleukin-7, interleukin-12, and GM-CSF gene transfer in patients with
      metastatic melanoma.

PMID- 8528752
TI  - Arnold Aberman, MD.
AB  - When the United States embarked on its effort to provide universal health
      insurance, the Canadian Medicare System was cited as a possible model for
      American health care. Often touted as an example of low-cost, high quality
      medicine, the Canadian system has mirrored the problems of health care across its
      southern border. With rocketing health care expenditures and financing having
      largely been decentralized to the individual provinces, local officials have
      struggled to cut costs and services. A central focus of these efforts has been a
      move to decrease the numbers of physicians, most notably a 10% decrease in
      medical school class size in 1993. While some Western provinces have experimented
      with the privatization of health care, the Canadian system still remains the
      epitome of government operated fee-for-service medicine. Given the likelihood of
      dramatic change in the American Medicare system, Canadian academic centers offer
      a unique perspective on the impact of capitation, evolving relationships with
      government payors, and the flip side of market oriented reforms. At the helm of
      one of Canada's largest schools is Arnold Aberman, MD, dean of the University of
      Toronto Faculty of Medicine. Born in Montreal, Quebec, Aberman received his MD
      from McGill University, but then did his residency both in Canada and the US,
      followed by a pulmonary fellowship at Albert Einstein College of Medicine and the
      Cardiovascular Research Institute of the University of California, San Francisco.
      Interviewed at his office in Toronto, Aberman reflected on the trials and
      tribulations confronting medicine on both sides of the 48th parallel.

PMID- 8528753
TI  - Physiologic and molecular aspects of the Na+/H+ exchangers in health and disease
      processes.

PMID- 8528754
TI  - Abnormal vascular function following ischemia-reperfusion injury.
AB  - Ischemia-reperfusion injury as a general rule is accompanied by dramatic changes
      in basal and reactive vascular function in most organs. There are similarities in
      altered organ vascular function, particularly in the first 24 to 48 hours, with
      decreased basal organ blood flow, hypersensitivity to vasoconstrictor stimuli,
      attenuated responses to vasodilators, and increased vascular permeability. The
      reduced responsiveness to endothelium-dependent vasodilators may be due to
      reduced endothelial NOS activity or to spontaneous maximal activation of NOS/NO
      activity, which cannot be stimulated further by endothelium-dependent agents.
      There are also notable quantitative and qualitative differences in ischemia
      reperfusion injury vasoreactive response in organs such as kidney, heart, and
      brain, the basis of which is unexplored, but may reflect regional differences in
      endothelium and/or organ parenchyma. Further examination of both the mechanisms
      and consequences of ischemia-reperfusion injury to the vasculature, as well as
      the clinical implications, should be a rewarding pursuit in organ
      pathophysiology.

PMID- 8528755
TI  - Cholesterol and coronary heart disease: predicting risks in men by changes in
      levels and ratios.
AB  - BACKGROUND: Little is known about the relative ability of different measures of
      change in cholesterol to discriminate coronary heart disease risk. We evaluated
      this ability for changes in low-density lipoprotein (LDL) cholesterol, high
      density lipoprotein (HDL) cholesterol, LDL/HDL ratios, and total cholesterol/HDL
      ratios. METHODS: We predicted risks of coronary heart disease using data from
      3641 men in the Lipid Research Clinics Coronary Primary Prevention Trial.
      Treating these patients as a cohort, we estimated risks associated with changes
      in cholesterol levels independent of the patients' randomization group. RESULTS:
      Changes in LDL and HDL cholesterol when used in combination were each significant
      predictors of coronary heart disease risk (odds ratios [OR] for 10% increases,
      1.15 and 0.84, respectively; P < 0.001). Changes in LDL/HDL and total
      cholesterol/HDL ratios had similar discriminating ability (OR for 10% increases,
      1.17 and 1.21, respectively; P < 0.0001). In the best discriminating models,
      changes in ratios added information about risks to changes in LDL cholesterol,
      although changes in LDL cholesterol levels failed to add information to changes
      in ratios. CONCLUSIONS: Changes in total cholesterol/HDL and LDL/HDL ratios were
      better predictors of risk for coronary heart disease than were changes in LDL
      cholesterol levels alone. When assessed as percentage changes averaged during the
      first two months of intervention, they were among the best discriminators of
      risk. Clinicians selecting treatments for intervention should include among their
      considerations the treatment's effect on both LDL and HDL cholesterol rather than
      their effects on LDL cholesterol levels alone.

PMID- 8528756
TI  - Regulation of calcium-activated potassium channels by S-nitrosothiol compounds
      and cyclic guanosine monophosphate in rabbit coronary artery myocytes.
AB  - BACKGROUND: The patch-clamp technique was used to study a large conductance,
      calcium-activated potassium channel (IK(Ca) in coronary arterial smooth muscle
      cells from rabbits. The properties of this channel are similar to those of IK(Ca)
      found in many types of vascular tissue. A brief single channel characterization
      of IK(Ca) in this tissue type has been completed for this study. METHODS: The
      effects of S-nitrosothiol compounds on IK(Ca) were studied in cell-attached
      patches. RESULTS: The probability of opening for IK(Ca) increased from 0.008 +/-
      0.004 to 0.780 +/- 0.07 following application of S-nitroso-L-cysteine. S-nitroso
      N-acetylpenicillamine (SNAP) also increased the probability of opening for IK(Ca)
      from 0.022 +/- 0.01 to 0.601 +/- 0.05. The probability of opening for IK(Ca) also
      increased from 0.026 +/- 0.01 to 0.809 +/- 0.02 following application of membrane
      permeable analogs of cyclic guanosine monophosphate (cGMP) to the bath of cell
      attached patches, suggesting that IK(Ca) in coronary artery smooth muscle cells
      is regulated by a cGMP-dependent mechanism. Rp-8-pCPT-cGMP, a protein kinase G
      inhibitor, blocked the effect of SNAP, an S-nitrosothiol compound. CONCLUSIONS:
      These findings suggest that one of the effects of nitrosothiol compounds is the
      activation of IK(Ca) through a cGMP-dependent mechanism in coronary artery smooth
      muscle cells.

PMID- 8528757
TI  - Informed consent for research: a study to evaluate readability and processability
      to effect change.
AB  - BACKGROUND: Ninety million Americans are reported to have low literacy skills,
      and the problems associated with illiteracy permeate all areas of our society,
      including medical research. The purpose of this study was to determine the
      readability and comprehensibility of human research informed consent forms using
      established reading comprehension processes. Further, if comprehension problems
      were present in the forms, the study sought to identify the exact nature of these
      difficulties and identify specific areas where the forms could be rewritten to
      increase readability and understanding. METHODS: All human research informed
      consents approved by Hartford Hospital in 1993 were evaluated by a Readability
      and Processability Form (RPF) based on reading research, including the Fry Scale
      which yields an approximate grade reading level. The RPF assigned points to each
      of the 20 areas of analysis according to strict scoring criteria, and target
      scores were established by the authors in consultation with the hospital.
      RESULTS: Seventy-six informed consent forms were evaluated, and neither the Fry
      score or the RPF score was in the target range. Ninety-six percent of the forms
      were found to have readability levels higher than the target level (8th grade).
      The mean readability and processability score was 46, resulting in the
      classification, Minimally Adequate/Needs Improvement. (The target range was Good,
      61-100.) A question by question analysis of each of the 20 checklist items on the
      RPF identified important aspects of text writing style that were scored as
      Unacceptable or Poor. CONCLUSIONS: The descriptive data indicates that there were
      problems with the readability of the informed consent documents studied. The
      prescriptive portion of this study provides researchers with information on
      specific areas where their forms need to be studied and rewritten. The
      comprehension problems found in this study may alert others to similar problems
      and may provide the basis for other institutional review boards (IRBs) to study
      their consent forms in order to ensure that the interests of both the patient and
      the researcher are protected and that the obtained consent is truly informed.

PMID- 8528758
TI  - A comparison of performance of mathematical predictive methods for medical
      diagnosis: identifying acute cardiac ischemia among emergency department
      patients.
AB  - BACKGROUND: There is increasing interest in mathematical methods for the
      prediction of medical outcomes. Three methods have attracted particular
      attention: logistic regression, classification trees (such as ID3 and CART), and
      neural networks. To compare their relative performance, we used a large clinical
      database to develop and compare models using these methods. METHODS: Each
      modeling method was used to generate predictive instruments for acute cardiac
      ischemia (which includes acute myocardial infarction and unstable angina
      pectoris), using prospectivel-collected clinical data on 5773 patients, who
      presented over a two year period to six hospitals' emergency departments with
      chest pain or symptoms suggesting acute ischemia. This data set was then split
      into training (n = 3453) and test (n = 2320) sets. Of 200 available variables,
      modeling was restricted to those available within the first 10 minutes of
      emergency department care (history, physical exam, and electrocardiogram).
      RESULTS: When the number of variables was limited to eight, representing a
      practical number for input in the real-time clinical setting, the logistic
      regression's receiver-operating characteristic (ROC) curve area, as a measure of
      diagnostic performance, was 0.887; the classification tree model's ROC curve area
      was 0.858, and the neural network's ROC curve area was 0.902. When the number of
      variables used by a model was not limited, the logistic regression's ROC area was
      0.905, the classification tree model's 0.861, and the neural network's 0.923.
      Among these models the neural networks had noticeably poorer calibration. When
      the outputs from each of these unrestricted models were presented to each of the
      other methods as an additional independent variable, the ROC areas of the new
      "hybrid" models were not significantly better than the original unlimited models
      (ROC areas 0.858 to 0.920). CONCLUSIONS: Logistic regression, classification
      tree, and neural network models all can provide excellent predictive performance
      of medical outcomes for clinical decision aids and policy models. Their ultimate
      limitations seem due to the availability of the information in data (a "data
      barrier") rather than their respective intrinsic properties. Choices between
      these methods would seem to be most appropriately based on the needs of the
      specific application, rather than on the premise that any one of these methods is
      intrinsically more powerful.

PMID- 8528759
TI  - Phage display: protein engineering by directed evolution.
AB  - Phage display of proteins has become an important tool for protein engineering.
      Over the past year, the versatility of the technology has expanded to include the
      development of DNA-binding proteins with novel specificities, energetics of
      protein folding and directed evolution of antibodies. In addition, display of
      expressed cDNA libraries opens an exciting opportunity for studying protein
      protein interactions.

PMID- 8528760
TI  - Antibody engineering.
AB  - Antibody engineering has been an extremely intensive research area for many
      years. Recent achievements discussed in this review include: (i) significant
      improvements in the field of selection of antigen-specific antibody fragments on
      bacteriophages; (ii) new structural work, in particular using NMR; (iii) the
      cloning of essentially the complete set of human VH genes; (iv) the use of
      antibodies to catalyze complicated chemical reactions; and (v) novel antibody
      fusion proteins to potentiate immune therapy. An interesting new development is
      the replacement of antibodies with more stable protein scaffolds for many future
      biotechnological applications.

PMID- 8528761
TI  - Native-like and structurally characterized designed alpha-helical bundles.
AB  - A number of coiled coils and alpha-helical bundles have recently been designed,
      and many have now been structurally characterized by X-ray crystallography.
      Others have not been as well characterized structurally but exhibit native-like
      properties in aqueous solution. Both areas of investigation have contributed
      greatly to our understanding of the nature of specificity in this class of
      molecules.

PMID- 8528762
TI  - Superantigen engineering.
AB  - Bacterial superantigens are extremely potent activators of the immune system.
      Their ability to efficiently cross-link molecules of the major histocompatibility
      complex class II and T-cell receptors causes the normal antigen specificity of
      each receptor to be bypassed. Two well characterized superantigens are the
      staphylococcal enterotoxins A and B. Data from mutagenesis studies in combination
      with recent structural information allow the definition of the surfaces on these
      superantigens involved in the binding of either type of receptor. Wild-type and
      engineered mutants of these superantigens have been used to modulate the activity
      of cells in the immune system, in an attempt to develop therapeutics
      applications.

PMID- 8528763
TI  - Structures of bacterial immunoglobulin-binding domains and their complexes with
      immunoglobulins.
AB  - Three-dimensional structures are now available for several immunoglobulin binding
      domains from bacterial proteins A, G, and L. X-ray diffraction and NMR
      experiments on complexes of these domains with portions of immunoglobulins have
      revealed common structural themes used in these interactions. These data expand
      our understanding of structure/function relationships in these molecular
      recognition processes and provide the basis for rational design of artificial
      immunoglobulin-binding molecules.

PMID- 8528764
TI  - Folding of beta-sheet proteins.
AB  - In the past year, interesting new information concerning various aspects of the
      folding process of beta-sheet proteins has been gleaned. Kinetic and equilibrium
      folding intermediates have been characterized. Studies of extensively denatured
      states and of model peptide fragments have enabled important steps to be taken
      towards an understanding of the initiation of the folding process of beta-sheet
      proteins. Site-directed mutagenesis has been used in combination with various
      probes to monitor folding events.

PMID- 8528765
TI  - Characterization and modeling of membrane proteins using sequence analysis.
AB  - The current libraries of amino acid sequences of membrane proteins are a valuable
      resource for the analysis of elements common to these proteins. Multiple-sequence
      alignment techniques and the identification of conserved features of
      transmembrane segments have improved the prediction of membrane protein topology.
      Molecular modeling in combination with structural studies or site-directed
      mutagenesis is proving to be a powerful link between theory and experiment.
      Unfortunately, the number of high-resolution structures of intrinsic membrane
      proteins, although increased recently, presents a restricted and perhaps biased
      view of membrane protein structure.

PMID- 8528766
TI  - Molecular mimicry in channel-protein structure.
AB  - The approach to probing the sequence-structure relationship of ion-channel
      proteins using small peptides stems from the abundance of sequence information
      and the virtual absence of structures at atomic resolution. It is anticipated
      that model peptides may fold predictably into stable structures and reproduce
      functional properties of specific proteins. Model peptides are well suited to the
      application of NMR methods to determine protein structure in a membrane
      environment or to high-resolution X-ray diffraction analysis. It is timely to ask
      what we have learned through this strategy and where it may lead in our quest to
      understand the sequence-structure determinism.

PMID- 8528767
TI  - Molecular mechanisms of protein-mediated membrane fusion.
AB  - Two recent X-ray structures shed new light on the molecular mechanisms by which
      viral proteins mediate membrane fusion. In both cases it is clear that the fusion
      proteins are capable of dramatic conformational rearrangements. Studies of the
      intracellular fusion machinery used in vesicular transport have also advanced
      rapidly, although high-resolution structural information is not yet available.

PMID- 8528768
TI  - Ion channel forming colicins.
AB  - Entry of proteins into membranes and transmembrane ion channel formation are two
      fundamental aspects of membrane biology. The ion channel forming colicins
      beautifully exemplify both properties. Recent results delineate the structure of
      a whole colicin; coupled with new biophysical studies, a mechanism for insertion
      is proposed.

PMID- 8528769
TI  - Structure, function, and membrane integration of defensins.
AB  - Defensins comprise a structural class of small cationic peptides that exert broad
      spectrum antimicrobial activities through membrane permeabilization. Their
      predominantly beta-sheet structure, stabilized by three disulfide bonds,
      distinguishes them from other antimicrobial peptides which typically form
      amphiphilic helices. Defensins bind to membranes electrostatically and
      subsequently form apparently multimeric pores. Recent structural and biophysical
      studies are beginning to provide insights into the process of permeabilization.

PMID- 8528770
TI  - The morphology of lipid membranes.
AB  - Current research into the morphology of lipid membranes focuses on three areas:
      first, the transformations and fluctuations of the shape of freely suspended
      vesicles; second, the morphology of membranes that experience mutual interactions
      or external forces arising, for example, from a macroscopic surface or from
      optical tweezers; and third, the behavior of heterogeneous membranes with respect
      to bilayer asymmetry; intramembrane domains and anchored polymers. Our
      understanding of the morphology of lipid membranes has progressed substantially
      through the development of experimental techniques and theories.

PMID- 8528771
TI  - Bending membranes to the task: structural intermediates in bilayer fusion.
AB  - Merger of lipid bilayers plays a central role in diverse biological fusion
      reactions. Recent studies suggest that different membrane fusion systems,
      including fusion of purely lipid bilayers, involve formation of similar stalk
      type intermediates--highly bent (net negative curvature) and transient lipidic
      connections between fusing membranes.

PMID- 8528772
TI  - Kinetics of lipid phase changes.
AB  - In the past two years, the kinetics of transitions involving the assorted
      lamellar and inverted hexagonal and cubic phases in bulk hydrated lipid systems
      have been established using a variety of physical techniques. In several cases,
      the kinetic data have lead to a transition mechanisms being deciphered.

PMID- 8528773
TI  - Engineering and design.

PMID- 8528774
TI  - Membrane proteins.

PMID- 8528775
TI  - Lipids.

PMID- 8528776
TI  - Influence of age on symptoms and signs in lumbar disc herniation.
AB  - In a prospective and consecutive study we evaluated the prevalence of pain
      related symptoms, the results of the straight leg raising (SLR) test and
      neurological disturbances by age group in a total of 150 patients operated on due
      to lumbar disc herniation. On admission, all patients were interviewed, and pain
      at rest, at night and on coughing was recorded. Walking capacity was recorded
      under four categories: > 5 km, 1-5 km, 0.5-1 km and < 0.5 km. Results of the SLR
      test were also registered as category data: positive 0-30 degrees, positive 30-60
      degrees, positive > 60 degrees or negative. Findings from examination of tendon
      reflexes and power of the extensor hallucis longus (EHL) muscle were registered,
      as were sensory disturbances. The above mentioned parameters were analysed
      separately for five different age groups: 20-29 years, 30-39 years, 40-49 years,
      50-59 years and above 60 years of age. There was an age-related change in the
      prevalence of certain parameters. Highly restricted positive SLR test results and
      pain on coughing was most commonly found in the youngest patient group. With
      increasing age there was a decreasing prevalence of highly restricted positive
      SLR test results, while the prevalence of severe reduction of walking capacity
      increased. In short, the youngest patient group showed the most obvious clinical
      picture of disc herniation and, with increasing age, the clinical picture
      gradually changed towards the picture associated with spinal stenosis.

PMID- 8528777
TI  - Magnetic resonance imaging before chemonucleolysis for lumbar disc prolapse.
AB  - Chemonucleolysis is an established non-operative treatment of a prolapsed
      symptomatic lumbar disc. It was introduced as a form of treatment in the early
      1960s by Smith [18]. One of the main causes of failure is the difficulty in pre
      operative assessment of a contained disc prolapse. Reducing failure rates is very
      important for the morale of surgeon and patient alike. We investigated 58
      patients with magnetic resonance imaging (MRI) to select those with a contained
      protrusion prior to chemonucleolysis. Per-operative discography confirmed
      contained protrusion in 96.5% (56/58) of cases, increasing the specificity of
      selection. At 6 months post chemonucleolysis 86% of our patients were
      asymptomatic. We would commend MRI as the investigation method of choice prior to
      chemonucleolysis for a prolapsed symptomatic lumbar disc, thus avoiding separate
      diagnostic discography, thereby reducing inconvenience to the patient and wastage
      of prepared chymopapain.

PMID- 8528778
TI  - Pocket-size, portable surface EMG device in the differentiation of low back pain
      patients.
AB  - The relevance of surface EMG of the paraspinal muscles measured by a portable,
      pocket-size device with a special amplifier was evaluated in different low back
      pain groups. Patients with only local low back pain had significantly higher EMG
      activities than those with unilateral radiating pain without verified disc
      herniation, those with verified disc herniation, and controls, but there were no
      differences between the latter three groups. Pain clearly modified paravertebral
      muscle activity, as the patients experiencing pain during the recording showed
      significantly higher EMG activities than those with no pain. It is concluded that
      surface EMG is a valid tool for indirectly assessing pain in low back pain
      patients but not for classification into different diagnostic groups.

PMID- 8528779
TI  - Epidural scar tissue formation after spinal surgery: an experimental study.
AB  - Extensive epidural scar formation is a well-known complication after spine
      surgery. Fibrous adhesions around nerve roots are a major reason for recurrent
      neurological symptoms following lumbar discectomy. A large variety of materials,
      implanted onto the dura, have been used to prevent or reduce laminectomy
      membrane, with conflicting results. We therefore carried out an experimental
      study in dogs to compare those materials that seemed to be most suitable. In each
      of 30 adult beagles, three lumbar laminectomies were performed. Each level was
      covered with a different material--free autologous fat graft, cellulose mesh,
      Gelfoam or triamcinolone suspension. In a control group nothing was implanted.
      After 7 days or 1, 3 or 6 months the animals were killed. The lumbar vertebral
      columns were harvested and prepared for further histological examination. To
      compare the results, we designed a new classification scheme (scar index). The
      data were obtained without knowledge of implanted material or time since
      operation. We found that free autologous fat grafts are able to reduce epidural
      scar formation in a high proportion of cases, especially after 3 and 6 months;
      cellulose mesh showed the worst results. We conclude that free autologous fat
      grafts are superior to other materials because of simple operative handling, good
      compatibility and effective prevention of laminectomy membrane.

PMID- 8528780
TI  - Haemodynamic changes in lumbar nerve root entrapment due to stenosis and/or
      herniated disc of the lumbar spinal canal--a magnetic resonance imaging study.
AB  - A prospective MRI study was carried out to assess the secondary changes in
      patients with stenosis and/or herniated disc of the lumbar spinal canal. The
      study covered 100 patients who had low back and leg pain due to such processes.
      Of these, 60 patients (group A) had a monoradicular pain pattern, average
      duration 2 months, due to a herniated lumbar disc. The remaining 40 patients
      (group B) had acute exacerbation of their chronic low back and leg pain, due to
      stenosis and herniated disc. As a control group, 5 asymptomatic volunteers with
      neither stenosis nor herniated disc on MRI were examined. All the patients and
      volunteers were examined by MRI with several sequences: partial saturation
      recovery with phase contrast PS (500/10), spin echo SE (500/20), short TI
      inversion recovery STIR (1900/135/30) and, for the dynamic study, field-gradient
      echo sequences FAST (50/15): 10 frames in 200 s. In all participants, Gd-DTPA was
      administered intravenously. In 8 of the patients of group B capillarisation in
      the protruded nucleus tissue was demonstrated on the PS sequence after Gd-DTPA
      administration. This tissue also showed decreased signal intensity on the STIR
      sequence. The capillarisation extended into the centre of the disc. Venous stasis
      could be verified in all of the 100 patients. An oedema could be verified in all
      patients of group A; in 20%, its size exceeded that of the herniated disc. In
      group B, an oedema was seen in only 12 patients. In the control group, no
      haemodynamic changes were seen. Using MRI, it is possible to define the border
      between herniated disc tissue and perifocal oedema.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8528781
TI  - School screening for scoliosis: the value of quantitative measurement.
AB  - Several studies advocate quantification of the bending test or performing surface
      topography to reduce the referral rate and to increase the specificity of the
      bending test in screening for scoliosis. Within the framework of a school
      screening project all children with a positive bending test were reexamined with
      measurement of rib hump height, angle of trunk rotation and moire topography. In
      the period 1983-1986, out of three cohorts of 10,000 children of 10, 12 and 14
      years of age, 3,069 were reexamined, of whom 1931 again tested positive (63%).
      The value of the three techniques in terms of sensitivity and specificity within
      the reexamined group was evaluated with regard to the Cobb angle on a spinal
      radiograph, which was made in 671 cases. A reduction in referrals of 37% was
      found. No significant difference in the ability to detect scoliosis was found
      between the three techniques mentioned. It is concluded that measurement
      techniques are valuable in school screening programmes. In particular, if instead
      of a single cut-off value, a range within which the examination should be
      repeated is chosen, high sensitivity and high specificity can be combined. Angle
      of trunk rotation measurement seems to be the easiest method of screening.

PMID- 8528783
TI  - Atlantoodontoid osteoarthritis: comparison of lateral cervical projection and CT.
AB  - The purpose of this study was to assess the accuracy of lateral cervical spine
      radiography in the detection of degenerative atlantoodontoid (AO) osteoarthritis,
      with CT as gold standard. In 50 patients, lateral radiographs and CT of the AO
      joint were blindly and independently graded by two radiologists: 0 = normal, 1 =
      mild degenerative disease, 2 = severe degenerative disease. Radiography was most
      accurate in distinguishing absent or mild disease from severe disease (83%
      sensitivity, 84% specificity). Sensitivity in distinguishing absent disease from
      mild or severe disease was 87%. Specificity, however, was low (52%), due to
      overestimation of the degenerative involvement on radiography. It is concluded
      that conventional radiography is a useful technique in screening for AO
      osteoarthritis, especially in severely degenerated joints. However, CT provides
      the best radiographic detail necessary for accurate diagnosis.

PMID- 8528782
TI  - Clinical efficacy of pedicle instrumentation and posterolateral fusion in the
      symptomatic degenerative lumbar spine.
AB  - Eighty-five patients with degenerative lumbar spine disease and radiologic
      evidence of instability, all older than 50 years (mean age 63.4 years), underwent
      transpedicular lumbar CD-spondylodesis and posterolateral fusion between 1987 and
      1992; 30 of them (mean age 60.8 years) had posterior lumbar interbody fusion
      (PLIF) additionally. The patients were followed up for a mean period of 32
      months. Of these patients, 86% improved with respect to their pain symptoms, but
      only 46% showed a good to excellent overall result. Patients with fair and poor
      outcomes had had significantly more operations on the lumbar spine (P < 0.001),
      had a greater extent of preoperative lumbar kyphosis (P < 0.05), had a larger
      preoperative motor weakness (P < 0.05), and had less vertebral slips (P < 0.01)
      than patients with good to excellent outcomes. Patients treated with
      transpedicular spondylodesis plus PLIF did not make any better progress than
      those with transpedicular fusion alone. By the 6-month follow-up a significant
      difference in the clinical outcome was already apparent (P < 0.001), making an
      improvement of a then fair or poor result unlikely.

PMID- 8528784
TI  - Traumatic atlantooccipital dislocation with survival: case report and review of
      the literature.
AB  - We present the case of a patient with traumatic atlantooccipital dislocation. The
      initial neurological examination showed no abnormalities. Dislocation was the
      result of rapid deceleration in a motor vehicle accident. The mechanism of injury
      was hyperextension/rotation, probably combined with a distraction force. Only a
      few cases of atlantooccipital dislocation without neurological involvement have
      been reported. Every report pointed out difficulties of initial diagnosis.
      Special attention should be directed toward the atlanto-odontoid-basion
      relationships as seen on lateral radiographs. Prompt recognition and surgical
      stabilization are essential to avoid further neurological injury.

PMID- 8528785
TI  - Atlantoaxial instability in a 7-year-old boy associated with traumatic disrupture
      of the ossiculum terminale (apical odontoid epiphysis).
AB  - A case of atlantoaxial instability with a rare etiology in a boy of 7 years and 3
      months is presented. Computerized tomography with three-dimensional
      reconstruction revealed avulsion of the ossiculum terminale (apical odontoid
      epiphysis). Developmental peculiarities and relevant disorders of the infantile
      upper cervical spine are discussed. Temporary posterior C1/C2 fusion and
      transdental screw fixation of the ossiculum terminale were attempted in order to
      stabilize C1/C2 and avoid permanent fusion. After removal of the dorsal implants,
      the transdental screw broke, the instability recurred and a permanent
      atlantoaxial fusion had to be performed.

PMID- 8528786
TI  - Thoracic fracture-dislocations without spinal cord injury: a case report and
      literature review.
AB  - Severe fracture-dislocation of the thoracic spine without neurological deficit is
      rare. Both translational and rotational deformity of the midthoracic spine makes
      transection of the cord almost inevitable due to the confined dimensions of the
      cord and spinal canal. Even though associated fractures of posterior elements are
      frequently seen, they seldom result in neural sparing. The case of a 24-year-old
      man who sustained a severe rotational fracture-dislocation of T9/T10 with
      considerable anterolateral displacement is reported. Due to a fractured left
      pedicle and a right-sided vertical fracture through the posterior aspect of the
      vertebral body, alignment of the posterior elements in the spinal canal was
      maintained and there was no neurological deficit. The patient was operatively
      treated with posterior segmental instrumentation, and was completely asymptomatic
      at follow-up 5 years later.

PMID- 8528787
TI  - Anterior evacuation of a spontaneous cervical epidural hematoma.
AB  - The case of a spontaneous cervical epidural hematoma treated by anterior
      corporectomy and arthrodesis is reported. An anterior approach is preferable when
      an epidural hematoma is anterior to the dural sac and when MRI shows an aspect of
      old clotted blood that can not be easily evacuated by a posterior laminectomy.

PMID- 8528788
TI  - Trends in births outside marriage.
AB  - The sharp rise in births outside marriage has been one of the most striking
      trends in fertility in recent years. Statistics from OPCS birth statistics and
      the Longitudinal Study are used in this article to summarise the main trends in
      births outside marriage in England and Wales. The differences in extra-marital
      fertility between social classes are then examined, as well as patterns of low
      birthweight.

PMID- 8528789
TI  - The review of parliamentary constituency boundaries--the reduction in the
      variation in electorates.
AB  - This article analyses how far the recent review by the Parliamentary Boundary
      Commission for England reduced the variation in the electorates of parliamentary
      constituencies. A comparison is also made with the equivalent results of the
      previous review. The factors which make equality of electorates impractical are
      outlined.

PMID- 8528790
TI  - Differences in mortality by housing tenure and by car access from the OPCS
      Longitudinal Study.
AB  - Housing tenure and household access to a car are useful indicators of socio
      economic status. They are simple to collect and process in censuses and surveys,
      and are effective discriminators of mortality. They can be used for all members
      of the population including children, women and the retired. These are groups
      where socio-economic differences in mortality based on occupation can be
      difficult to interpret. Using Longitudinal Study data, this article presents an
      analysis of differences in male and female mortality in England and Wales in the
      1980s according to household tenure and car access. The findings are compared
      with those observed in the 1970s. Mortality levels are lower in the 1980s for all
      groups. The analyses suggest that differences across tenure and car access groups
      have increased in relative and absolute terms, particularly for those under 65.

PMID- 8528791
TI  - 1993-based subnational population projections for England.
AB  - The populations of the shire counties and Greater London are projected to
      increase in population between 1993 and 2001. In contrast the populations of the
      metropolitan counties are expected to remain fairly static. This article gives
      details of the 1993-based subnational population projections for local authority
      areas within England.

PMID- 8528792
TI  - Living together in Great Britain--displaying household structure through
      demographic pyramids.
AB  - Population pyramids are a demographic technique which can be used to represent
      the age and sex structure of a population. This article illustrates how the
      technique can be used to represent the age and sex distribution of co-resident
      members of households. The pyramids use data from the 1% household file of the
      Samples of Anonymised Records from the 1991 Census of Great Britain. Some
      comparisons are made with Spanish households.

PMID- 8528793
TI  - Population review. Structure and distribution of the population.
AB  - This article is the first in a series of articles reviewing the changing
      composition of the population of the United Kingdom. The series is a follow-up to
      the demographic reviews published in the mid-1970s and mid-1980s (see In Brief,
      page 2). This first article gives a summary view of the changes since the early
      Seventies in the structure and distribution of the UK population, and also takes
      account of population projections for future years. It begins by describing
      changes in the total population. The review then goes on to consider changes in
      sex ratios, age distribution, marital status, the regional distribution of the UK
      resident population, population density, ethnicity and household composition.

PMID- 8528794
TI  - The art of ultrasound in obstetrics: from abstraction to hyper-realism.

PMID- 8528795
TI  - Blood flow velocity waveforms of the abdominal arteries in appropriate- and small
      for-gestational-age fetuses.
AB  - The aim of this study was to describe flow velocity waveforms of abdominal
      arteries in the appropriate- and small-for-gestational-age fetus. Splenic artery,
      superior mesenteric artery, hepatic artery and renal artery velocity waveforms
      were obtained from 57 appropriate-for-gestational-age and nine small-for
      gestational-age fetuses with color flow Doppler ultrasonography. The pulsatility
      index was used to quantify the arterial waveforms. Repeated measure analysis of
      variance indicated significant differences in the pulsatility index values in
      both the appropriate-for-gestational-age and small-for-gestational-age fetuses. A
      multiple comparison test revealed a significantly lower value for the pulsatility
      index in the splenic artery when compared to that of the other vessels for both
      the appropriate- and small-for-gestational-age fetuses. In the small-for
      gestational-age fetuses, a lower pulsatility index value was observed at the
      superior mesenteric artery level when compared to the renal artery. Because of
      its lower frequency of successful insonation, the hepatic artery was not
      considered for the analysis. In the normal fetus, the splenic artery had the
      lowest pulsatility index when compared to the other arteries we investigated.
      This difference remained in small-for-gestational-age fetuses, reflecting a lower
      vascular resistance at the fetal spleen in both normal and small-for-gestational
      age fetuses. It appears that in small-for-gestational-age fetuses the renal
      artery has a higher pulsatility index than the superior mesenteric artery,
      suggesting a preferential distribution of blood flow to the bowel.

PMID- 8528796
TI  - Changes observed in Doppler studies of the fetal circulation in pregnancies
      complicated by pre-eclampsia or the delivery of a small-for-gestational-age baby.
      I. Cross-sectional analysis.
AB  - The aim of this study was to compare changes in Doppler ultrasound studies of the
      fetal circulation in normal pregnancies with a group of pregnancies complicated
      by proteinuric pregnancy-induced hypertension (PPIH), delivery of a small-for
      gestational-age (SGA) baby, or both. A total of 167 uncomplicated pregnancies
      with a term delivery of an appropriately grown baby (AGA) were used to define the
      normal range. Altogether, 123 high-risk pregnancies with a known outcome
      constituted the study group. A color duplex ultrasound machine was used to
      perform biometry and fetal Doppler studies. Measurements obtained from the fetal
      circulation included the umbilical artery (UA) pulsatility index (PI), the middle
      cerebral artery (MCA) PI and time-averaged velocity (TAV), the thoracic aorta
      (AO) PI and TAV. In addition, the ratio between the MCA PI and UA PI, the MCA PI
      and the AO PI, and the product of the MCA PI and AO TAV were used in the
      analysis. A total of 105 pregnancies had a complicated outcome. They were divided
      into three categories: PPIH only (pregnancies complicated by PPIH with the
      delivery of an AGA fetus, n = 17), SGA only (delivery of an SGA baby, with no
      evidence of PPIH, n = 55), and PPIH + SGA (pregnancies complicated by pre
      eclampsia and delivery of an SGA baby, n = 37). The PPIH + SGA group represented
      true clinical intrauterine growth retardation. Cross-sectional reference ranges
      were created using the observations from the normal group. z-scores (standard
      deviation from the mean of the normal range) of the last observations made before
      delivery were calculated for each of the vessel velocimetry measurements and
      ratios. The statistical significance of z-score values was calculated using
      analysis of variance. The MCA and UA PI values showed the greatest deviation for
      any single-vessel parameter. The ratios of fetal Doppler indices (MCA/UA PI
      ratio, MCA/AO PI ratio and the MCA PI/AO TAV index) demonstrated greater
      deviation from normal than any individual vessel. The UA PI z-score for PPIH+SGA
      delivering < 34 weeks gestation (2.92) was significantly greater than the z-score
      for PPIH+SGA delivering > or = 34 weeks (1.20, p < 0.05). Fetal Doppler indices,
      in particular ratios that include measurements obtained from the cerebral
      circulation, help in the recognition of the small fetus that is growth-retarded.
      At term, evidence of fetal hemodynamic redistribution may exist in the presence
      of a normal umbilical artery PI. Fetal Doppler indices provide information that
      is not readily obtained from more conventional tests of fetal well
      being.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8528797
TI  - Isolated pericardial effusion: an indication for fetal karyotyping?
AB  - The outcome and associations of 35 consecutive cases of isolated pericardial
      effusion detected in the fetus are presented. In all cases included in the study,
      there was no evidence of a structural abnormality or a rhythm disturbance
      detectable antenatally. Karyotyping revealed that 26% of cases had trisomy 21 and
      31% of the total had some form of chromosomal anomaly. Our study shows that the
      outlook for isolated pericardial effusion is good. However, there is a high
      incidence of associated karyotypic anomalies, in particular trisomy 21. Fetal
      karyotyping is therefore recommended in these cases.

PMID- 8528798
TI  - Spontaneous regression of fetal pulmonary sequestration.
AB  - The prenatal diagnosis of pulmonary sequestration can usually be made by the
      third trimester of pregnancy, from the combination of an intrathoracic mass and
      indirect signs such as cardiac deviation, fetal hydrops, pleural effusion and
      polyhydramnios. We describe four cases in which pulmonary hyperechogenicity was
      detected before 26 weeks' gestation. In three cases the hyperechogenic mass was
      isolated. In all cases it had mostly regressed during the pregnancy. A review of
      the cases of isolated pulmonary sequestration that have been diagnosed during the
      antenatal period is presented. Antenatal evolution was found to be unpredictable
      regardless of the type or severity of the case at the first diagnosis. We propose
      a classification to define more clearly the optimal management of pulmonary
      sequestration.

PMID- 8528799
TI  - Resolving fetal hyperechogenic lung lesions: an unresolved issue.

PMID- 8528800
TI  - Fetal lung hyperechogenicity: prenatal ultrasonographic diagnosis, natural
      history and neonatal outcome.
AB  - The ultrasonographic appearance of fetal lung hyperechogenicity is most commonly
      associated with congenital bronchopulmonary abnormalities, such as cystic
      adenomatoid malformation or pulmonary lobar sequestration. Spontaneous
      disappearance of echogenic lung lesions has rarely been reported, mainly due to
      in utero resolution of cystic adenomatoid malformation. We describe four fetuses
      with echogenic lungs detected prenatally, none of them having been proved to have
      adenomatoid malformation or pulmonary sequestration of the lungs. Color Doppler
      sonography was used prenatally in all cases to rule out pulmonary sequestration.
      Three of the four fetuses showed complete resolution of the lung lesions during
      gestation, with normal neonatal outcome, but in one where the lesion decreased in
      size, intrauterine demise occurred at 28 weeks' gestation before complete
      resolution, and pneumonia was found at autopsy. We suggest that fetal lung
      hyperechogenicity may result from in utero bronchial tree obstruction with
      retention of mucoid fluid distal to the obstruction. With advancing gestation, in
      some cases the relative obstruction may be relieved, and the sonographic
      appearance of the lungs may return to normal. A retention of mucus in the
      bronchial tree should be added to the differential diagnosis of hyperechogenic
      lung lesions detected by antenatal ultrasound examination.

PMID- 8528801
TI  - Predictive value of antepartum ultrasound examination for anomalies in twin
      gestations.
AB  - The purpose of this study was to evaluate the accuracy of antenatal
      ultrasonography in the detection of fetal anomalies among twin gestations cared
      for in a specialized antepartum twin clinic. A retrospective study was performed
      of 245 consecutive twin gestations followed in our twin clinic. The sensitivity,
      specificity and diagnostic indices of ultrasound to detect prenatal anomalies in
      the 490 infants delivered from July 1988 to October 1994 were determined.
      Fourteen infants had isolated congenital anomalies, and ten had multiple
      anomalies. The overall prevalence of congenital anomalies was 4.9%. Antepartum
      ultrasound examination had a sensitivity of 88% and a specificity of 100% for the
      detection of an anomalous infant, with a positive predictive value of 100% and a
      negative predictive value of 99%. The sensitivity of ultrasound for each
      individual anomaly within the cohort was 82%, with 100% specificity, 100%
      positive predictive value, and 98% negative predictive value. Our conclusions are
      that serial antepartum ultrasound examination of twins for congenital anomalies
      in our institution is very specific, with high positive and negative predictive
      values. The sensitivity, while also excellent, has limitations, which should be
      discussed with the patient.

PMID- 8528802
TI  - Doppler parameters of the ovarian and uterine blood circulation in ovarian
      hyperstimulation syndrome.
AB  - Nine in vitro fertilization (IVF) patients with moderate or severe ovarian
      hyperstimulation syndrome (OHSS) were recruited for a longitudinal study. Twenty
      four unselected, asymptomatic patients undergoing similar IVF treatment were used
      as controls. OHSS was diagnosed 8-13 days after oocyte retrieval. All subjects
      were examined with pulsed color Doppler ultrasound. The pulsatility index (PI)
      and the maximum peak systolic velocity of the uterine and the intra-ovarian
      arterial blood flow were measured. There were no significant differences in the
      mean PI or the maximum peak systolic velocity of the uterine and intra-ovarian
      arterial blood flow between symptomatic patients and controls during the first
      examination. At the resolution of symptoms, however, the mean PI of the uterine
      artery was significantly lower in pregnant patients with OHSS than in pregnant
      controls (p < 0.01). The development of the OHSS could not be explained by the
      circulatory conditions observed in the intra-ovarian and uterine arteries.

PMID- 8528803
TI  - Sonographic assessment of birth weight among breech presentations.
AB  - The objective in this study was to determine whether there was a difference in
      the accuracy of sonographically determined birth weight estimate in fetuses
      presenting by the breech as compared to the vertex. Prospectively, 104
      consecutive singleton fetuses presented by the breech presentation were
      identified who also had a sonographic estimate of birth weight within 72 h of
      delivery. The control group (n = 104) consisted of fetuses presenting by the
      vertex of women who had the following hospital number and who were of similar
      demographic characteristics; the birth weight estimate in the control group had
      to be within 100 g of that of the women with the breech fetus. The estimate of
      the birth weight was derived for both groups using seven published models.
      Prediction limits were calculated for an estimated vs. actual birth weight for
      parturients with breech presentation. Among the study group, the mean
      standardized absolute error was similar for the seven models (range 120 +/- 104
      to 138 +/- 118 g/kg; p = 0.08). For six of the models, the mean standardized
      absolute error was significantly higher for fetuses in the breech presentation
      than for fetuses in vertex presentation (range 80 +/- 63 to 112 +/- 95 g/kg; p =
      0.02 to < 0.0001). Prediction limit calculations indicate that 99% of the time
      the actual birth weight was between 1500 and 3999 g if the estimate of birth
      weight was 2400-2900 g. We conclude that, for fetuses in a breech presentation,
      the error with most models is significantly higher than for a singleton in the
      vertex position.

PMID- 8528805
TI  - Fetal ductus arteriosus--how far may it bend?

PMID- 8528804
TI  - Korotkoff's sounds in pregnancy.
AB  - Korotkoff described the sequence of vascular sounds heard with a stethoscope over
      the brachial artery during deflation of a pneumatic cuff. The initial sounds are
      produced by vibrations of the vessel wall, although the sequence of vascular
      sounds has frequently been ascribed to 'turbulence' of flow in the vessel. This
      study has been performed to determine the relationship between the vascular
      sounds (Korotkoff I-V) produced during blood pressure cuff deflation and specific
      changes in the brachial artery waveform. Ten nulliparous women admitted to
      hospital in the third trimester of pregnancy have been studied by means of
      concurrent Doppler ultrasound and phonocardiography. Changes in the brachial
      artery waveform during blood pressure cuff deflation were recorded using Doppler
      ultrasound (7.5 MHz) with concurrent objective demonstration of phases I-V of the
      vascular sounds using a phonocardiography microphone. Characteristic features of
      the brachial artery waveform were associated with phases I-IV of the vascular
      sounds in all patients (10/10). No consistent features of the brachial artery
      waveform were associated with phase V of the vascular sounds. Phases I-IV of the
      vascular sounds are associated with specific changes in the pattern and direction
      of flow within the brachial artery in normotensive primigravid women. The
      vascular sounds produced by vibration of the vessel wall are modulated by changes
      in blood flow to produce the characteristic sequence of vascular sounds detected
      with a stethoscope during blood pressure cuff deflation.

PMID- 8528806
TI  - First clinical experience with sonicated human serum albumin (Albunex) as an
      intrafallopian ultrasound contrast medium.
AB  - The safety and preliminary efficacy of a new ultrasound contrast medium. Albunex
      for evaluating Fallopian tube patency during transvaginal sonography were studied
      in seven women. All of the women had sought medical attention because of uterine
      fibroids and excessive menstrual bleeding and were scheduled for a subsequent
      hysterosalpingectomy 3 weeks after the ultrasound examination. Albunex was
      injected transcervically in doses ranging from 0.5 to 9 ml, alternating with
      saline, during concomitant transvaginal ultrasound scanning. There were no
      serious adverse reactions. Peroperative macroscopic and postoperative microscopic
      investigations of the endometrium. Fallopian tubes and peritoneal biopsies
      revealed no pathological changes. Agreement between hysterosalpingo contrast
      sonography (HyCoSy) and postoperative testing for the evaluation of tubal patency
      was observed in 12 out of 14 Fallopian tubes. These findings suggest that Albunex
      may safely be used as an intrafallopian contrast medium in ultrasound
      investigations.

PMID- 8528807
TI  - Antenatal diagnosis and management of meconium peritonitis: a case report and
      review of the literature.
AB  - We present a case of meconium peritonitis which was associated with a short bowel
      and complicated by progressive bowel distension and difficulty in making a
      definitive diagnosis of cystic fibrosis. Treatment was by bowel resection and an
      ileostomy (and later bowel anastomosis), followed by parenteral nutrition which
      was complicated by hepatitis. The literature is reviewed and management dilemmas
      and options are discussed.

PMID- 8528808
TI  - Effects of thyrotropin releasing hormone on cardiac and extracardiac flows of
      appropriately grown and growth-retarded fetuses.
AB  - The objective of this study was to establish the effect of thyrotropin releasing
      hormone on the fetal circulation of appropriately grown and growth-retarded
      fetuses. Doppler recordings were performed immediately before and 15 min after
      maternal administration of 400 micrograms of thyrotropin releasing hormone in 14
      women with appropriately grown and 19 with growth-retarded fetuses. Furthermore,
      in six women with growth-retarded fetuses, serial recordings were performed at 2
      hourly intervals for 8 h until a second thyrotropin releasing hormone dose was
      administered. Velocity waveforms were recorded from the outflow tracts, inferior
      vena cava, umbilical artery, middle cerebral artery and descending aorta, and
      different Doppler indices calculated. In appropriately grown fetuses, thyrotropin
      releasing hormone induced a significant increase of peak systolic velocity values
      in the aorta and pulmonary artery and an increase of Doppler-estimated cardiac
      output. In growth-retarded fetuses, these changes were more evident and
      associated with a significant decrease in reverse flow in the inferior vena cava
      during atrial contraction. No changes were observed in fetal heart rate or in the
      other fetal vessels investigated. In the growth-retarded fetuses followed
      longitudinally, these changes were evident for the following 8 h and were
      potentiated by the second thyrotropin releasing hormone administration. In
      conclusion, thyrotropin releasing hormone induces significant hemodynamic effects
      on the fetal heart that may temporarily improve the impaired cardiac function of
      growth-retarded fetuses.

PMID- 8528809
TI  - Childhood sexually transmitted diseases and child sexual abuse: results of a
      Canadian survey of three professional groups.
AB  - The purpose of this national survey was to determine the knowledge and attitudes
      of Canadian health and social services professionals about the occurrence of
      sexually transmitted diseases (STDs) in children and its implications for child
      sexual abuse. A mailed questionnaire was sent to a randomly selected sample of
      4,500 nurses, physicians, and youth/social workers across the country. Response
      rates varied from over 60% of nurses and youth/social workers to only 38% of the
      physicians. Nurses and youth/social workers were younger than physicians, had a
      proportionately higher number of females within their groups, and more frequently
      reported that they had or might have been sexually abused as children. Although
      there was no statistically significant difference among the groups on the
      composite knowledge score, physicians scored higher than the other two groups on
      knowledge about STDs, and youth/social workers had the highest knowledge scores
      about sexual abuse. Some differences in attitudes among the groups were also
      noted. Overall, the rates of respondents reporting confidence in their ability to
      treat children with STDs or child sexual abuse were low (26% and 35%
      respectively). This paper presents the overall results of the survey, and makes
      recommendations for strategies to enhance professional expertise in the area.

PMID- 8528810
TI  - Interdisciplinary training in the evaluation of child sexual abuse.
AB  - To increase their knowledge of the medical evaluation and reporting of child
      sexual abuse, medical students, pediatric resident physicians, fellows and
      attendings participated in an interdisciplinary team-based training program
      consisting of didactic lectures, case discussions, videotapes and direct
      participation in patient evaluation. Content focused on the medical knowledge and
      skills needed for an assessment of the child's interview, anogenital examination
      and the indications for case reporting to child protection authorities. We
      evaluated the results of this training in our outpatient child abuse clinic
      located in a university-affiliated, municipal hospital using a survey which
      assesses knowledge of female genital anatomy, sexually-acquired diseases and case
      reporting in a nonrandomized control trial. Fifteen medical students and
      pediatric physicians participated and were compared to a reference group of 127
      participants who did not receive this training and 15 others who randomly
      repeated the survey instrument during the study period. The results showed that
      resident physicians demonstrated increased mean total scores in the survey
      instrument. We conclude that an interdisciplinary team using patient care
      exposure increases physician knowledge in the evaluation of child sexual abuse.

PMID- 8528811
TI  - [Prevalence and sequelae of childhood sexual abuse in Spain].
AB  - The aim of this research was to determine the prevalence of sexual abuse in Spain
      and its long and short effects. A representative sample of Spanish society was
      studied (N = 1.821) through proportional stratified random sampling. Data were
      obtained by interview (Personal History of Sexual Abuse), carried out in the
      subjects home and by means of a Self Reporting Questionnaire (S.R.Q.), which the
      interviewer gave the subject to be returned by post. The results show a high
      prevalence of sexual abuse prior to age 17 (15% of males and 22% of females) with
      short-term effects (lack of trust, disgust, fear, hostility towards the
      aggressor, shame, anxiety, etc.) and in long-term a greater tendency towards
      mental health problems (F = 7.7; p < .01), as well as other problems throughout
      the life cycle (running away from home, school failure, sexual dissatisfaction,
      drug-taking, etc.). The high prevalence and the clear long and short effect make
      prevention programs and help for the victims advisable.

PMID- 8528812
TI  - Placement outcomes of 206 severely maltreated children in the Boston Juvenile
      Court system: a 7.5-year follow-up study.
AB  - This study examines placement outcomes of 206 severely maltreated children 7.5
      years after arraignment in Boston Juvenile Court (BJC) on Care and Protection
      Petitions. Sixty-seven percent (n = 138) of the sample had been permanently
      removed from their parents and 33% (n = 68) had their cases dismissed in the BJC.
      At time of this follow-up, 21% of the full sample (n = 44) were still in
      temporary custody awaiting permanent placement. In addition, 4% (n = 8) of
      children had "drifted" back to their abusive/neglectful parents despite prior
      permanent removal. The average time children in this sample spent in probate
      proceedings (awaiting permanent placement) had increased substantially to 2.1
      years since the last overview study of this sample 4 years ago. The rate of court
      referral for incidences of reabuse (a C&P filing), or delinquency was
      significantly lower among children who had been permanently placed (p < .003).
      Rates of court-referral for reabuse charges were the same (16%) for children who
      were in temporary custody at the time of follow-up and children who had been
      dismissed back to the parent for whom the original C&P had been filed. Results
      are discussed in light of the urgent need to restructure time limits in juvenile
      court proceedings, integrate adequate tracking of child abuse and neglect cases
      through and across court and agency boundaries, and the use standardized
      assessments of abused and neglected children as a tool in the adjudication
      process.

PMID- 8528813
TI  - Association of drug abuse and child abuse.
AB  - OBJECTIVE: To show that children born to mothers who used drugs during pregnancy
      were at a higher risk of subsequent abuse or neglect than were children from the
      general population. METHODOLOGY: This is a retrospective-prospective study of
      abuse experiences of children born at an urban medical center between January
      1985 and December 1990 to women who used illicit drugs during pregnancy. Children
      exposed in-utero to drugs were identified using results of toxicology screens
      from birth and maternal records. Evidence of abuse was obtained from the State
      Central Registry of Abuse and Neglect. The registry contained information on all
      reported abuses or neglects, the types, findings, and outcomes of the
      investigations of reported cases. The outcome measure was whether the children
      had been abused or not during the study period. RESULTS: One hundred and fifty
      five (30.2%) of the 513 children exposed in-utero to drugs were reported as
      abused or neglected and 102 (19.9%) had substantiated reports giving a rate of 84
      abuse and neglect cases per 1,000 years of exposure. The yearly substantiated
      abuse rates varied, the lowest being 30 cases per 1,000 years of exposure in 1986
      and the highest 107 cases per 1,000 in 1987. This rate was two to three times
      that of children living in the same geographic area in the south side of Chicago.
      Neglect was reported in 72.6% of cases, with the toddlers being the most
      vulnerable to abuse and neglect. Natural parents were responsible for
      maltreatment 88% of the time. On logistic regression analysis, the risk of abuse
      of children increased 1.56-fold (Confidence Interval = 1.25-2.01) that of
      nonabusing parents among women who had completed high school education or had
      some college education and 1.80-fold among women with previous planned abortion,
      after controlling for confounding variables. Other sociodemographic variables of
      the child or mother did not significantly increase the odds of abuse.
      CONCLUSIONS: Infants exposed in-utero to drugs have a higher than expected risk
      of subsequent abuse compared to children in the general population.

PMID- 8528815
TI  - Visible but unreported: a case for the "not serious enough" cases of child
      maltreatment.
AB  - This study examined the psychosocial characteristics of cases of child
      maltreatment labelled as "not serious enough." The sample consisted of cases of
      suspected physical abuse (N = 48), neglect (N = 13), and psychological
      maltreatment (N = 8) identified by teachers, and a nonabused comparison group (N
      = 283). Characteristics of children and their parents were evaluated at three
      ecological levels: individual, family, and social. Results indicated a poor
      personal and social adjustment of the children in the maltreatment groups, and
      suggest that the definition of cases of maltreatment as not serious enough does
      not represent the psychological reality of these children. Discriminant analysis
      indicated that the most important variables for discriminating between all
      maltreatment groups and the nonabuse group were parents and children's
      perceptions of parental behavior, children's behavioral problems and personal
      adjustment, parents integration and satisfaction in the community, and the
      importance and direction of personal growth emphasized in the family. The
      importance of other variables such as socioeconomic status, stress, psychological
      symptoms or number of children appeared to be a function of the different types
      of child maltreatment. The importance of prevention and intervention efforts
      before the maltreatment reaches a serious stage is discussed.

PMID- 8528814
TI  - Parental attitude and practice regarding physical punishment of school children
      in Santiago de Chile.
AB  - Four hundred and twenty-three parents from two free, nonconfessional, public
      schools placed in medium and low income areas, and 104 parents from a private,
      for-pay Catholic school in a medium and high income zone filled out an anonymous
      self-applied survey to learn attitudes and practices regarding child physical
      punishment. In the for-pay school parents declared better education. Child
      battering was admitted by 80.4% (public schools) and 56.7% (private school)
      despite that 34.1% (public schools) and 51.9% (at the private school) declared
      that battering should never be used. Females admitted and justified physical
      punishment in higher proportions than males. Poor school performance, defiance,
      and running away from home were the preferred reasons to justify battering at
      public schools, while defiance was preferred at the private school where poor
      performance was sent to the fourth place. To check parents data and get
      children's opinions, 192 seventh and eighth grades students were surveyed in one
      public school (n = 84) and the private school (n = 98). At the public school,
      85.7% of children, and 54.1% of the children at the private school admitted to
      having been physically punished, with no sex differences. Stronger rejections to
      this punishment were found at the private school. Mother (87 [5%] at the public
      school and 77 [4%] at the private) and father (36 [1%], and 67 [9%],
      respectively) were singled out as leading users of physical punishment. Physical
      punishment differences according to social environment were detected while
      eradication seems difficult given its cultural basis.

PMID- 8528816
TI  - When educators confront child abuse: an analysis of the decision to report.
AB  - Five scenarios of child abuse were used to study the recognition and reporting of
      child abuse in a sample of 664 teachers, counselors, school psychologists,
      principals, and district superintendents. The following results emerged: (a)
      Reporting tendency varied by type of abuse described, forming a 3-level
      hierarchy; (b) reporting tendency and reporting rate were unrelated to the gender
      of the victim or respondent; (c) reporting tendency was unrelated to the
      profession of the educator (i.e., principal, counselor, etc.), though certain
      types of abuse were suspected and/or reported significantly less often by
      classroom teachers; (d) for each scenario a linear composite of decisional items
      discriminated Reporters from Nonreporters with 75% to 84% accuracy. Most salient
      in distinguishing Reporters from Nonreporters were issues involving quality of
      suspicion and the respondents belief that schools should be a first line of
      defense against abuse and neglect; (e) educators were uniform in their high level
      of awareness of mandatory reporting laws; (f) educators preparedness to detect
      child abuse differed by profession, but most desired additional training. The
      implications of these findings are reviewed and suggestions made for revisions to
      social service policies and training for educators.

PMID- 8528818
TI  - Munchausen by proxy victims in adulthood: a first look.
AB  - Very little is known about the long-term impact of Munchausen by Proxy abuse on
      children, as many victims probably are never identified and most have been lost
      to follow-up soon after termination of protective services supervision. This
      exploratory study examined the childhood experiences and long-term psychological
      outcomes for 10 adults, ranging from 33 to 71 years of age, who were self
      identified victims of illness fabrication by a parent. Subjects completed a 33
      item questionnaire including demographic and open-ended questions and a checklist
      of PTSD symptoms, supplemented by telephone interviews. Subjects described a
      range of experiences from poisonings and induced bone fractures to symptom
      exaggeration. Subjects generally felt unloved and unsafe in childhood; a few were
      directly aware of their parent's deceptions. They made limited attempts to alert
      others, with little success. Subjects reported significant emotional and physical
      problems in childhood, and problems in adulthood including insecurity, reality
      testing issues, avoidance of medical treatment and posttraumatic stress symptoms.
      Most of their siblings were also abused, physically or medically. Some subjects
      express considerable residual anger towards the abusing mothers, but a surprising
      degree of sympathy for the fathers who passively colluded or failed to protect.
      Some of the MBPS parents have continued fabricating their own medical illnesses
      or harassing their adult children with fabricated dramas even decades later.

PMID- 8528817
TI  - Risk of child abuse or neglect in a cohort of low-income children.
AB  - The purposes of this research were to identify risk factors for reported child
      abuse or neglect and to examine the roles of stress and social support in the
      etiology of child maltreatment. Mothers of newborn infants with biomedical and
      sociodemographic risk factors were recruited from community and regional
      hospitals and local health departments in 42 counties of North and South Carolina
      selected for geographic distribution and for large numbers of such newborns. For
      every four such mothers, the next mother to deliver an otherwise normal newborn
      was sought. Mothers were interviewed shortly after giving birth, and state
      Central Registries of Child Abuse and Neglect were reviewed when each infant was
      1 year of age. Eight hundred forty-two of 1,111 recruited mothers were
      successfully interviewed in their homes between March 1986 and June 1987. Seven
      hundred forty-nine North Carolina births who resided in the state more than 6
      months were eligible for inclusion in the analysis. Logistic regression with
      backward elimination procedures was used in the analysis. Maternal education (p <
      .01), number of other dependent children in the home (p < .01), receipt of
      Medicaid (p < .01), maternal depression (p < .05), and whether the maternal
      subject lived with her own mother at age 14 years (p < .05) were the best
      predictors of a maltreatment report. Further examination revealed an interaction
      effect between stressful life events, as measured by life event scores, and
      social well-being (p < .01). For children born at risk for social and/or medical
      problems, extreme low income (participation in public income support programs),
      low maternal education, maternal depression, the presence of any other young
      children in the home, and a mother's separation at age 14 years from her own
      mother significantly predict child maltreatment reports in the first year of
      life. In addition, stressful life events, even if perceived positively, may
      increase or decrease the risk of maltreatment reports, depending upon the
      presence of social support.

PMID- 8528819
TI  - Treatment in child sexual abuse.

PMID- 8528820
TI  - Outcome of therapy for sexually abused children: a repeated measures study.
AB  - The outcome of abuse-focused treatment was examined in a sample of 105 sexually
      abused children, 71 of whom completed 3 months of treatment or longer. Symptom
      change was measured with the Trauma Symptom Checklist for Children (TSCC; Briere,
      in press) and the Children's Depression Inventory (CDI; Kovacs, 1983, 1992),
      administered at 3 month intervals. The CDI and all TSCC scales but Sexual
      Concerns decreased after 3 months of therapy, and of these, all but Dissociation
      continued to decline at one or more assessment periods thereafter. At 6 months,
      those remaining in therapy continued to decrease on the CDI and on the Anxiety,
      Depression, Post-traumatic Stress, and Sexual Concerns scales of the TSCC. At 9
      months Anxiety and Post-traumatic Stress continued to decrease, and at 1 year
      those still in treatment showed decrements in Anxiety, Depression, and Post
      traumatic Stress. These changes are hypothesized to be due to treatment per se,
      rather than merely as a result of the passage of time. In this regard, multiple
      regression analyses indicated that time from the end of abuse to either the
      beginning or the end of treatment was far less predictive of post-treatment TSCC
      or CDI scores than was number of months specifically spent in treatment.

PMID- 8528821
TI  - The efficacy of group treatment in sexually abused girls.
AB  - The efficacy of the outpatient, once a week group treatment of sexually abused
      girls was examined using a pre-post, matched control/treatment design. The 30
      girls were 9-12 years old, within 1 year of trauma, and were screened for
      psychosis. The Quay Revised Behavioral Problem Checklist (RBPC) and the Eyberg
      Child Behavior Inventory (ECBI) were used as dependent measures, and given 6
      months apart. Depending on the scale, and excepting the RBPC's Psychotic Behavior
      Scale, 60-100% of the girls had abnormal scores pretreatment, with no significant
      differences between the two groups. Significant (p < .001) treatment effects were
      found. After treatment, 0-33% of the treated girls had abnormal scores, while 60
      100% of the control group continued to have abnormal scores. Assuming
      generalization is possible, it appears that this and similar treatment programs
      are effective in reducing the girls' perceived problematical anxiety and
      misbehavior.

PMID- 8528822
TI  - Resilience criteria and factors associated with resilience in sexually abused
      girls.
AB  - Alternative measures of resilience and correlates of resilience were examined in
      a sample of 43 sexually abused girls who were assessed using a self-administered
      interview at the time of intake for psychotherapy. Results indicated relatively
      high levels of disagreement as to which girls were resilient using maintenance of
      social competence and absence of clinical levels of symptomatology as alternative
      criteria. Most girls that had maintained age-normative levels of social
      competence were, nonetheless, manifesting clinically significant levels of
      symptoms. A warm and supportive relationship with a nonoffending parent was a
      strong correlate of resilience, regardless of which criteria was used. Lower
      levels of abuse related stress, fewer negative cognitive appraisals of the
      abusive relationship, and less reliance on aggressive coping behaviors were also
      significant predictors of resilience based on the absence of clinical levels of
      symptomatology. However, parental support and level of abuse stress were the only
      two variables to enter a logistic regression model predicting resilience. The
      research and clinical implications of these findings are discussed.

PMID- 8528823
TI  - The coming changes in tax-exempt health care finance.
AB  - On December 30, 1994, the Internal Revenue Service (IRS) published proposed
      regulations (Proposed Regulations) that if enacted would significantly change the
      climate and rules of federal income tax law controlling the issuance and
      maintenance of tax-exempt bonds for governmental and 501(c)(3) health care
      borrowers. This article (1) summarizes the aspects of the Proposed Regulations
      dealing with private activity tests, management contracts, allocation and
      accounting rules, change in use of financed facilities, and antiabuse rules, and
      (2) summarizes the possible interrelationship of the IRS's audit program for tax
      exempt bonds and the Proposed Regulations. The article reviews features of the
      Proposed Regulations that will affect either the costs or administrative burdens
      of managing the federal tax compliance of future tax-exempt health care
      borrowings.

PMID- 8528824
TI  - Financing medical office buildings.
AB  - This article discusses financing medical office buildings. In particular,
      financing and ownership options from a not-for-profit health care system
      perspective are reviewed, including use of tax-exempt debt, taxable debt, limited
      partnerships, sale, and real estate investment trusts (REITs).

PMID- 8528825
TI  - Any possibility of an S & L-type debacle occurring in the health industry?
AB  - The geographically linked health networks with their integrated health
      maintenance organizations (HMOs), now gaining such awesome market penetration and
      fiscal power, and the projected cutbacks in Medicare and Medicaid reimbursement
      could conceivably set the stage for similar underlying conditions that led in the
      late 1980s to the savings and loan (S & L) debacle. Some would argue that to
      promise health services to the indigent and the working poor and their dependents
      is bestowing an entitlement to low-income families that is analogous to the
      taxpayers previously providing fiscal relief to upper-income savers with the S &
      L bailout. Although parallels are drawn throughout this article between our
      current procompetitive health industry and the thrifts before the S & L crisis,
      it is concluded that it is unlikely a comparable societal and fiscal disaster
      will occur soon in the health field. What is more predictable is that the
      creditworthiness of some highly leveraged networks with poor-payer-classification
      patients will become so precarious that the federal government will initiate and
      administer a highly politicized "health care delivery relief fund" to bail out
      failed alliances and HMO plans.

PMID- 8528826
TI  - Economic credentialing moves from the hospital to managed care.
AB  - This article deals with the application of economic measures to the appointment,
      reappointment, and delineation of medical staff privileges, the so-called
      practice of economic credentialing. The concept of economic credentialing is
      first explored in the hospital context with a focus on legal and political
      issues. The second part of the article examines how economic credentialing will
      evolve in new managed care practice settings. Emphasis is placed on how the law
      and legislation will be utilized by organized medicine to protect physician
      interests in the process of selective contracting. Specific discussion focuses on
      the American Medical Association's Patient Protection Act and the implications of
      "any willing provider" provisions.

PMID- 8528827
TI  - Long-term care insurance and alternatives: a comparison of employer and
      individual policy markets.
AB  - This article presents findings from a recently completed Health Insurance
      Association of America-sponsored survey that sought to measure the extent to
      which long-term care insurers paid for newer, long-term care alternatives. The
      focus of the survey was on payment for three services: adult day care, board and
      care homes, and assisted living facilities. The survey also collected information
      on companies offering reimbursement for these services under an alternate care
      benefit (i.e., a plan of nonconventional care and services that can serve as an
      alternative to more costly inpatient nursing home care). Survey data showed that
      long-term care insurance sold in employer markets reimburses a richer set of
      alternative long-term care benefits than policies sold in individual markets. In
      addition, the majority of employer market companies reimburse for alternatives
      under their base policy, recognizing the importance of payment for
      noninstitutional, long-term care alternatives.

PMID- 8528828
TI  - The use of case management services in long-term care insurance policies.
AB  - This article presents findings from a recently completed Health Insurance
      Association of America-sponsored survey that sought to measure the extent to
      which long-term care insurers utilize case/care management services in their
      policies. The survey sought to measure the extent to which long-term care
      insurers paid for newer, long-term care alternatives. Contrary to previous
      findings in the literature, the survey results show that case management services
      are typically delivered through a combination of internal and external networks,
      and are utilized primarily by insurers in employer markets. In light of national
      health care reform, these survey results indicates a need to reexamine the role
      of case management in delivering long-term care services, particularly within
      private financing mechanisms such as long-term care insurance.

PMID- 8528829
TI  - Gloria Niemeyer Francke is fourth recipient of Donald E. Francke Medal.

PMID- 8528830
TI  - Detailed planning to upgrade the sterile-products preparation area to a
      cleanroom.
AB  - In a project to establish a cleanroom, the pharmacy manager is the person who
      must motivate everyone and keep the momentum going. Involving departments other
      than pharmacy is the key to success. The project provides an opportunity to
      improve the department's performance with the aid of other departments.

PMID- 8528831
TI  - Shark cartilage for cancer treatment.

PMID- 8528832
TI  - An iconoclastic perspective on progress in pharmacy practice.
AB  - Progress in pharmacy practice is examined and areas for improvement are
      identified. Data from surveys of hospital and health system pharmacy practice
      from 1957 to 1994 show that the steady progress from 1974 to 1985 was not
      sustained over the past decade. Changing to a profession in which all
      practitioners provide pharmaceutical care will be difficult when practice in
      hospitals, where the most acutely ill patients are treated, does not meet the
      profession's recommended standards. Many pharmacists may be resigned to a reality
      in which their services are viewed as ancillary. The number of medication
      misadventures that occur indicates that there is an unmet need for effective
      medication management. Pharmaceutical care offers the promise of better patient
      outcomes as well as "reprofessionalization" of pharmacists. To elevate the level
      of pharmacy practice, individual practitioners need will; too much attention has
      been given to skill. Many new practitioners have earned Pharm. D. degrees but not
      received enough nurturing from colleagues to develop into innovators who will
      continue the profession's progress. It is crucial that the pharmacy practice and
      education communities cooperate to prepare pharmacists to function in the
      changing health care system. Also, professional organizations must set aside
      their fragmented interests and focus together on pharmacists' survival. The
      restructuring and economic pressures in health care may offer pharmacists the
      opportunity for progress, since improving drug use would help to decrease health
      problems and cost.

PMID- 8528833
TI  - Torsemide: a new loop diuretic.
AB  - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and
      dosage and administration of torsemide are reviewed. Torsemide belongs to the
      pyridine-sulfonylurea class of loop diuretics. Its primary site of activity is
      the thick ascending limb of the loop of Henle, where it blocks active
      reabsorption of sodium and chloride, resulting in diuresis, natriuresis, and
      other effects. Torsemide has high bioavailability, a relatively long half-life,
      and a prolonged duration of activity. It is highly protein bound. Clinical trials
      indicate that torsemide is effective in the treatment of hypertension and of
      edema and other symptoms in patients with chronic renal failure (CRF), hepatic
      dysfunction, or congestive heart failure (CHF). Torsemide has infrequent, mild,
      and transient adverse effects; among the most common are orthostatic hypotension,
      fatigue, dizziness, and nervousness. The recommended initial oral dosages of
      torsemide are 10-20 mg/day for CHF, 20 mg/day for CRF, 5 mg/day for hypertension,
      and 5-10 mg/day (in combination with a potassium-sparing diuretic or aldosterone
      antagonist) for hepatic cirrhosis. In most patients, the pharmacokinetic
      advantages of torsemide over other loop diuretics are unlikely to translate into
      a substantial edge in clinical outcomes, and in practice there may be no cost
      advantages. Although torsemide does not offer major advantages over other loop
      diuretics, it may be of benefit in patients who do not respond to or cannot
      tolerate other agents.

PMID- 8528834
TI  - Prevention and treatment of diabetic nephropathy.
AB  - The pathophysiology and natural history of diabetic nephropathy are described,
      and recent developments in its prevention and treatment are discussed. Diabetic
      nephropathy can occur in both insulin-dependent and non-insulin-dependent
      diabetics. It is characterized by arterial hypertension, proteinuria, and
      progressive loss of renal function. Although the exact mechanism has not been
      fully elucidated, hyperglycemia with altered intraglomerular hemodynamics is an
      important contributor to the initiation and progression of the disease.
      Concurrent hypertension aggravates progression of the disease. Currently accepted
      strategies to slow the progression of diabetic renal disease have focused on
      antihypertensive therapy, strict glucose control, and restriction of dietary
      proteins. Recent publications support the hypothesis that angiotensin-converting
      enzyme inhibitors have a unique ability, independent of their antihypertensive
      effect, to slow the progression of diabetic nephropathy. Investigational agents
      (e.g., aminoguanidine) may prove helpful in the management of the condition.
      Information about the prevention of diabetic nephropathy has grown significantly
      in the past few years.

PMID- 8528835
TI  - Comprehensive services in an ambulatory care pharmacy.
AB  - The development of a comprehensive model of pharmacy practice in an ambulatory
      care setting is described. From 1991 to 1994, the department of ambulatory care
      pharmacy services at The University of Illinois at Chicago Medical Center
      converted its main outpatient pharmacy into a Pharmaceutical Care Center to serve
      as a model for community and hospital-based ambulatory care pharmacy services.
      The Pharmaceutical Care Center includes a waiting area, five private patient
      assessment rooms, an examination room, a place for reviewing patient profiles and
      reference materials, space for storage and automation, an i.v. admixture area, a
      conference room, and office space. It serves 120-150 patients per day (10% just
      discharged from the hospital, 90% seen in the clinic system). Pharmacy clerkship
      students and residents, under the oversight of faculty, conduct patient
      assessments, educate patients and family, monitor outcomes, and intervene when
      drug-related problems are detected. Patient assessments and therapeutic
      interventions are documented in the patient's medical record. Computers,
      automated medication filling, and technical support are used to enable
      pharmacists to concentrate on patient care. A model ambulatory care pharmacy
      provides both drug distribution and direct patient care services.

PMID- 8528836
TI  - Stability of ursodiol in an extemporaneously compounded oral liquid.
AB  - The stability of ursodiol in an extemporaneous oral liquid formulation
      refrigerated at 4 degrees C for 35 days was studied. A suspension was prepared by
      opening commercially available 300-mg capsules of ursodiol, adding Glycerin, USP,
      to form a paste, and then adding Simple Syrup, NF. A control solution was
      prepared from analytical-grade ursodiol powder in simple syrup. The final
      concentration of ursodiol in both formulations was 60 mg/mL. Three samples of
      each preparation were stored in 2-oz, amber glass prescription bottles in the
      dark at 4 degrees C. Immediately after preparation and at 7, 14, 21, 28, and 35
      days, samples were visually inspected, tested for pH, and assayed in duplicate by
      high-performance liquid chromatography. Stability was defined as the retention of
      more than 90% of the initial concentration. On day 35, the mean percentage of the
      initial ursodiol concentration remaining was 96.5% in the suspension made from
      powder-filled capsules, and 100.6% in the suspension made from analytical-grade
      powder. The color, odor, and pH of the samples did not change appreciably over
      the study period. An extemporaneously compounded oral liquid preparation of
      ursodiol in simple syrup was stable under the conditions studied for up to 35
      days.

PMID- 8528837
TI  - Technician checking of pharmacists computerized order entry for parenteral
      nutrient solutions.

PMID- 8528838
TI  - Policy to restrict use of i.v. bumetanide.

PMID- 8528839
TI  - Stevens-Johnson syndrome following erythromycin administration.

PMID- 8528840
TI  - ASHP statement on the role of the pharmacist in patient-focused care. American
      Society of Health-System Pharmacists.

PMID- 8528841
TI  - ASHP guidelines on pharmaceutical services in correctional facilities. American
      Society of Health-System Pharmacists.

PMID- 8528842
TI  - USP monographs and tests of radiochemical purity.

PMID- 8528843
TI  - Cost-effective treatment of atracurium resistance in critically ill patients.

PMID- 8528844
TI  - Lotteries set up for two experimental AIDS drugs.

PMID- 8528845
TI  - Planning for the ASHP Resident Matching Program.

PMID- 8528846
TI  - Evaluating the performance of a pharmacy benefit management company.

PMID- 8528847
TI  - Pharmacoeconomic principles.

PMID- 8528848
TI  - Effect of an automated, nursing unit-based drug-dispensing device on medication
      errors.
AB  - The effect of an automated drug-dispensing system on medication error rates was
      studied. Disguised observations were made on nursing units just before (phase 1)
      and two months after (phase 2) the implementation of Medstation Rx (Pyxis, San
      Diego, CA) at a 600-bed hospital. Information gathered included the time of drug
      administration, the time the medication as ordered to be given, a description of
      what happened during administration of the dose, and the type of medication
      error, if any. During phase 1 there were 873 observations and 148 medication
      errors, for an error rate of 16.9%. During phase 2 the error rate was 10.4% (97
      errors in 929 observations). In both study phases, most of the errors were wrong
      time errors. The mean +/- S.D. difference between actual and scheduled
      administration times was 34.5 +/- 48.9 minutes in phase 1 and 30.1 +/- 31.6
      minutes in phase 2. Both the decrease in the error rate and the decrease in the
      departure from scheduled administration times were statistically significant.
      Medstation Rx was associated with a reduction in the rate of medication errors at
      a large hospital.

PMID- 8528849
TI  - Cost-reducing treatment algorithms for antineoplastic drug-induced nausea and
      vomiting.
AB  - A treatment algorithm and preprinted order form developed to reduce the cost of
      treating antineoplastic drug-induced nausea and vomiting are described. A team
      including pharmacists, oncologists, and oncology nurses developed a treatment
      algorithm to reduce the cost of antiemetic therapy for patients receiving
      antineoplastic therapy at a 719-bed academic medical center. The algorithm
      incorporated the following concepts: matching antiemetic therapy with the
      emetogenic potential of the antineoplastic regimen, reducing ondansetron dosages,
      increasing the ratio of oral to intravenous therapy, and treating delayed-onset
      nausea and vomiting without using serotonin-receptor antagonists. To help
      physicians learn and use the treatment algorithm, it was incorporated into an
      order form for both antineoplastic and antiemetic drugs. Separate order forms
      were created for pediatric and adult patients. A comparison of outcome data
      before and after implementation of the practice guidelines showed that the
      patient outcomes were at least as good after implementation as before. More than
      a year after the guidelines were implemented, more than 85% of antiemetic
      regimens prescribed for antineoplastic drug-induced nausea and vomiting were in
      compliance with the guidelines. A cost avoidance of nearly $205,000 was realized
      in the first year. Collaboration with oncologists at the start of the care plan
      was a key element in its success. An antiemetic treatment algorithm, integrated
      with a preprinted physician order form, was well accepted and has reduced
      expenses for antiemetic therapy.

PMID- 8528850
TI  - Prime vendor purchasing of pharmaceuticals in the Veterans Affairs health care
      system.
AB  - The development of a prime vendor system of pharmaceutical procurement and
      distribution in the Department of Veterans Affairs (VA) is described. The
      traditional system of pharmaceutical procurement and distribution in the VA
      required large stockpiles of the pharmaceuticals that had been needed the
      previous year, a system that was inefficient and full of hidden markups and other
      unnecessary fees. In late 1991, the VA began a pilot test of a prime vendor
      system, in which three wholesalers were selected to provide pharmaceuticals to 33
      VA medical centers. Under the new system, pharmacies placed orders
      electronically, directly with the prime vendor, and payments were taken from
      funds obligated in advance. The benefits of the new system included reduced
      costs, faster turnaround of orders, higher fill rates, and higher satisfaction
      among users. In 1994, the VA ceased operation of its traditional depot system for
      pharmaceuticals. The implementation of a prime vendor procurement system for
      pharmaceuticals within the VA improved system responsiveness, increased
      satisfaction of system users, and reduced expenses.

PMID- 8528851
TI  - Safety and cost of rapid i.v. injection of famotidine in critically ill patients.
AB  - The safety and cost of famotidine in intensive care patients given the drug by
      rapid i.v. injection or slow i.v. infusion were studied. All patients admitted to
      the medical-coronary care and surgical intensive care units (ICUs) at a
      university teaching hospital over a two-month period who had orders for at least
      one dose of famotidine injection for any indication were randomly assigned to
      receive the drug by rapid i.v. injection or slow i.v. infusion via volumetric
      chamber. Data on patient demographics, drug administration time, adverse effects,
      cardiovascular variables, and costs (including drug acquisition, supply, and
      nursing personnel costs) were collected prospectively. Fifty-three patients
      received famotidine by i.v. injection (a total of 1041 doses) and 52 by i.v.
      infusion (1006 doses). The mean +/- S.D. duration of famotidine administration
      was 44 +/- 12 seconds in the i.v.-injection group and 19 +/- 5 minutes in the
      i.v.-infusion group. Adverse effects possibly related to famotidine occurred in
      three injection-group patients and two infusion-group patients. No significant
      difference between the groups in cardiovascular variables (mean arterial
      pressure, heart rate, and respiratory rate) was noted. Cost savings for the
      injection group relative to the infusion group totaled $2886 for the two-month
      study period. Half of the savings came from reduced supply costs and half from
      reduced personnel costs. The annualized savings to the institution would be about
      $17,300. Rapid i.v. injection of famotidine appeared to be as safe in ICU
      patients as giving the drug by slow i.v. infusion and was less costly.

PMID- 8528852
TI  - Medication knowledge and compliance among patients receiving long-term dialysis.
AB  - The extent to which patients receiving longterm dialysis understood and complied
      with their drug therapy regimens was studied. Patients undergoing long-term
      hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) in a university
      affiliated outpatient dialysis center were surveyed to determine their knowledge
      about and compliance with prescribed regimens for antihypertensives, phosphate
      binders, and calcitriol. They were asked to list their prescribed medications and
      state the medications' indications, the frequency with which they missed doses,
      and the actions they took after missing a dose. The patients were also asked
      where they obtained their medications and who their primary source of drug
      information was. Seventy-two patients (51 receiving hemodialysis and 21 receiving
      CAPD) were surveyed. Although 80% of the patients could recall the three target
      medications, only 39% of the hemodialysis patients and 57% of CAPD patients could
      recall all of their medications. Significantly more patients knew the indication
      for their antihypertensive medication and calcitriol than for their phosphate
      binder. The hemodialysis and CAPD patients reported they missed an average of
      13.0 and 4.7 phosphate binder doses, 2.6 and 5.6 antihypertensive doses, and 6.7
      and 7.0 calcitriol doses, respectively, per month. Despite the fact that 70% of
      the patients received their medications from a community pharmacy, less than 15%
      identified the pharmacist as their primary source of drug information. Patients
      receiving long-term hemodialysis or CAPD were more knowledgeable about and
      compliant with their antihypertensive and calcitriol regimens than their
      phosphate binder regimens.

PMID- 8528853
TI  - Effect of prescribing guidelines on the use of neuromuscular blocking agents.
AB  - The effect of prescribing guidelines on the use of neuromuscular blocking agents
      (NMBs) was studied. Voluntary guidelines on the appropriate prescribing of
      formulary NMBs in the operating rooms at a university hospital were approved in
      January 1993. Patients who underwent inpatient surgery with neuromuscular
      blockade during a preguideline period (March 1, 1992, through May 31, 1992) or a
      postguideline period (March 1, 1993, through May 31, 1993) were randomly selected
      (n = 200 per group) and compared to determine the relative appropriateness,
      effectiveness, safety, and cost of NMB use. The preguideline and post-guideline
      groups were demographically similar. There were significantly more instances of
      appropriate NMB use after than before the guidelines were established.
      Neuromuscular blockade was maintained inall patients. The overall rates of NMB
      associated adverse events were 5.5% and 7.5% for the preguideline and
      postguideline groups, respectively. The acquisition cost of NMBs and drugs used
      to treat NMB-associated adverse events for the preguideline patients was $4261,
      versus $2978 for the postguideline patients. Extrapolated to the estimated 10,000
      operations per year requiring neuromuscular blockade at the institution, the
      total cost was $213,000 before guideline introduction and $149,000 afterward, for
      a guideline-associated cost reduction of $64,000. Prescribing guidelines reduced
      expenditures for NMBs without affecting clinical outcomes.

PMID- 8528854
TI  - Stability and activity of alteplase with injectable drugs commonly used in
      cardiac therapy.
AB  - The stability, activity, and compatibility of alteplase with eight drugs
      frequently used in cardiovascular disease were studied. Alteplase 1 mg/mL was
      mixed with each of the following: heparin sodium 80 units/mL in 0.9% sodium
      chloride injection, dobutamine 10 mg/mL (as the hydrochloride salt) in 0.9%
      sodium chloride injection or 5% dextrose injection, dopamine hydrochloride 1.6
      mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, morphine
      sulfate 2 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection,
      lidocaine hydrochloride 8 mg/mL in 0.9% sodium chloride injection or 5% dextrose
      injection, propranolol hydrochloride 1 mg/mL, metoprolol tartrate 1 mg/mL, or
      nitroglycerin 0.8 mg/mL in 0.9% sodium chloride injection or 5% dextrose
      injection. Each mixture was assayed immediately and after storage for 24 hours at
      25 degrees C; mixtures containing heparin were also assayed at 4 hours. The
      alteplase concentration and percentage of the single-chain molecule in each
      mixture were analyzed by using size-exclusion high-performance liquid
      chromatography (HPLC). Alteplase bioactivity was determined by a clot-lysis
      assay. Drug concentrations were assayed by HPLC, pH values of the mixtures were
      determined, and the mixtures were visually inspected. Instability was defined as
      a > 10% decrease in concentration; inactivity was defined as a > 10% decrease in
      activity; incompatibility was defined as detection of a precipitate, opalescence,
      or color change. Alteplase was not stable in the presence of heparin sodium,
      morphine sulfate, or dobutamine and was not active in the presence of dopamine
      hydrochloride. Alteplase was compatible with and stable and active (in vitro) in
      the presence of lidocaine hydrochloride, propranolol hydrochloride, metoprolol
      tartrate, or nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528855
TI  - Stability of octreotide acetate in polypropylene syringes at 5 and -20 degrees C.

PMID- 8528856
TI  - Stability of ceftazidime (with arginine) in an elastomeric infusion device.

PMID- 8528857
TI  - Pharmacy benefit management companies.
AB  - The principal services offered by pharmacy benefit management companies (PBMs)
      are described. A PBM contracts with employers, insurers, and others to provide
      accessible and cost-effective benefits to those groups' members. PBMs vary in
      their organization and services because they originate from different types of
      businesses. Many PBMs have been formed by publicly traded companies that have
      combined traditional ways of controlling cost and use, such as formularies, with
      new elements to form organizations whose primary function is managing the
      pharmacy benefit. Often, the PBM is paid a fixed amount for which it must provide
      all contracted services. PBMs may provide pharmacy services themselves (e.g.,
      mail order prescription service is offered by Medco, one of the largest PBMs);
      more often, they subcontract with others to provide certain services. Full
      service PBMs have the following functions: establishing networks of pharmacies
      for use by plan members; processing claims electronically at the time a
      prescription is filled and thus maintaining a database on drug use and cost;
      using these data to generate various reports; encouraging the use of generic
      products; managing existing formularies, helping to establish customized
      formularies, or providing a national formulary; providing information to support
      formulary guidelines (counter-detailing); offering programs in which
      prescriptions for maintenance medications are filled less frequently with larger
      amounts, often by mail order; negotiating volume-based rebates from
      manufacturers; performing drug-use review; developing disease management programs
      based on clinical practice guidelines and measurements of patient outcome; and
      evaluating outcomes by combining data on drug therapy with information about
      other parts of the patient's care.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528858
TI  - Criteria for use of intravenous milrinone in adult inpatients.

PMID- 8528859
TI  - Fat-soluble vitamin capsules as stereotactic markers.

PMID- 8528860
TI  - Expiration dates and removal of i.v. bag overwrap.

PMID- 8528861
TI  - Debate on total nutrient admixtures continues.

PMID- 8528862
TI  - AMA house scrutinizes managed care prescription policies, decries payments to
      pharmacists for switches.

PMID- 8528863
TI  - Women happier than men in pharmacy career.

PMID- 8528864
TI  - Dyes for marking colonic lesions.

PMID- 8528865
TI  - Riding into battle without a pharm.D. degree.

PMID- 8528866
TI  - Immunotherapy in multiple sclerosis, Part 1.
AB  - The efficacies of corticosteroids and azathioprine (part 1) and of
      cyclophosphamide, immune globulin, cyclosporine, interferons, copolymer 1, and
      cladribine (part 2) in patients with multiple sclerosis (MS) are reviewed. MS is
      an inflammatory, demyelinating disease of the CNS that commonly affects young
      adults. The involvement of various immune mechanisms in MS suggests a role for
      immunomodulating therapy. The goals of immunotherapy vary with the clinical stage
      of the disease and include (1) improving recovery from exacerbations, (2)
      decreasing the number or severity of relapses, (3) preventing the development of
      chronic progressive disease from a relapsing-remitting course, and (4) decreasing
      further progression in patients with chronic progressive disease. In clinical
      trials, corticotropin and corticosteroids have been found to accelerate recovery
      from exacerbations. Tapering is often effective after high-dose induction
      therapy. Long-term maintenance regimens do not alter disease progression and are
      not recommended. Azathioprine produces modest benefits with respect to relapse
      rates and disease progression after two or more years of treatment; adverse
      effects are mild to moderate. Azathioprine should not be used in patients with
      aggressive disease who may approach severe disability in 6-18 months.
      Cyclophosphamide, because of its modest impact on disease progression and its
      potentially severe adverse effects, including cancer, should be reserved for
      patients with aggressive relapsing-remitting or chronic progressive disease in
      whom other treatments have failed to work; maintenance therapy is necessary after
      induction. Intravenous immune globulin may benefit patients with severe relapses;
      however, its efficacy remains unproven. Cyclosporine also cannot be recommended
      because of its modest efficacy, marked adverse effects, and high cost. Interferon
      beta-1b is a more specific immunotherapy that has been found to decrease the
      number and severity of relapses. This treatment should be considered in patients
      with relapsing-remitting disease who are having two or more exacerbations per
      year. Copolymer 1 and cladribine have shown some promising early results.
      Although various immunotherapeutic drugs can provide relief in patients with MS,
      none is capable of reversing disease progression, and some can cause serious
      adverse effects. Better understanding of the immunologic basis of MS may lead to
      more specific immunotherapies with more lasting benefits.

PMID- 8528867
TI  - Treatment of Kaposi's sarcoma with liposomal doxorubicin.
AB  - The efficacy of liposomal doxorubicin for treating Kaposi's sarcoma (KS) in
      patients infected with human immunodeficiency virus (HIV) was studied. Eight men
      with HIV infection and KS were to be given liposomal doxorubicin 20 mg/sq m i.v.
      monthly for six months and 10 mg/sq m i.v. monthly thereafter, depending on the
      response. They were assessed for the onset, extent, and duration of clinical
      response; relapse; adverse effects; development of new opportunistic infections;
      quality of life; and survival. Five patients had a clinical complete response
      (i.e., complete resolution of the manifestations of KS, as determined by physical
      examination but not confirmed by biopsy) and three patients had a partial
      response to the induction regimen of liposomal doxorubicin. Relapse occurred in
      all patients in whom therapy was stopped; reinstatement of therapy elicited a
      partial response. Neutropenia occurred in two patients; filgrastim therapy
      enabled the liposomal doxorubicin therapy to continue uninterrupted.
      Thromboembolic events developed or were suspected in three patients, although
      they may not have been caused by liposomal doxorubicin. Monthly i.v.
      administration of liposomal doxorubicin partially or completely eliminated the
      clinical manifestations of Kaposi's sarcoma in eight men infected with HIV.

PMID- 8528868
TI  - Predictors of organizational and career commitment among Illinois pharmacists.
AB  - Illinois pharmacists were surveyed to identify predictors of their work-related
      attitudes. A survey was mailed in April 1994 to 600 Illinois pharmacists to
      identify their attitudes about their career, the organization where they work,
      and the impact of national health care reform and the pharmaceutical care
      movement on the future of pharmacy. The survey also collected information on the
      respondents' work site and position; coworkers, family, and friends; and
      demographic characteristics. The survey was completed by 337 pharmacists.
      Pharmacists who believed that pharmaceutical care would have a more positive
      effect on pharmacy were more committed to their employer and to pharmacy as a
      career. Co-worker support had a positive effect on perceptions about
      pharmaceutical care, and supervisor support increased career and organizational
      commitment. Age did not affect career or organizational commitment, but it did
      negatively affect pharmacists' views of the impact that the call for
      pharmaceutical care would have on pharmacy. Hospital pharmacists were less
      committed than community pharmacists to the organizations where they worked.
      Practice setting, supervisor support, and perceptions about the impact of the
      pharmaceutical care movement were identified as possible predictors of career and
      organizational commitment.

PMID- 8528869
TI  - Stability of ondansetron hydrochloride injection in various beverages.
AB  - The stability of ondansetron hydrochloride injection in beverages likely to be
      acceptable to patients was studied. Ondansetron hydrochloride injection
      (containing ondansetron 2 mg/mL) was added to apple juice, fruit punch, cherry
      flavored drink, carbonated soft drinks, and hot tea to provide a nominal
      ondansetron concentration of 32.8, 64.5, or 95.2 micrograms/mL. Samples were
      stored at -3 to 28 degrees C (noncarbonated-beverage mixtures except tea), 2 to
      28 degrees C (carbonated-beverage mixtures), and 25 degrees C (tea) and assayed
      for ondansetron concentration by high-performance liquid chromatography at 6, 24,
      48, and 72 hours (noncarbonated-beverage mixtures except tea); 6, 24, and 48
      hours (carbonated-beverage mixtures); and 1 hour (tea). More than 95% of the
      initial ondansetron concentration was retained in apple juice, fruit punch,
      cherry-flavored drink, Sprite, and Diet Coke throughout the periods studied. A
      precipitate formed immediately after ondansetron was added to hot tea, but the
      drug was chemically stable for at least one hour in this preparation. Ondansetron
      hydrochloride injection 32.7, 64.5, and 95.2 micrograms/mL (expressed as free
      base) was stable in various beverages when stored at -3 to 28 degrees C for up to
      72 hours. Ondansetron at these same concentrations precipitated in hot tea
      preparations but was chemically stable for at least one hour.

PMID- 8528870
TI  - Aminoglycoside pharmacokinetics in Alaskan natives.

PMID- 8528871
TI  - Stability of midazolam hydrochloride in polyvinyl chloride bags under fluorescent
      light.

PMID- 8528872
TI  - Compatibility of midazolam hydrochloride and lorazepam with selected drugs during
      simulated Y-site administration.

PMID- 8528873
TI  - Stability of piperacillin sodium-tazobactam sodium in peritoneal dialysis
      solutions.

PMID- 8528874
TI  - Compatibility of tacrolimus injection with cimetidine hydrochloride injection in
      0.9% sodium chloride injection.

PMID- 8528875
TI  - The national voluntary certification program for pharmacy technicians.

PMID- 8528876
TI  - Pharmacist-managed ticlopidine clinic.

PMID- 8528877
TI  - Administration of terazosin capsules through feeding tubes.

PMID- 8528878
TI  - Drug reactions identified at resident physicians' morning report.

PMID- 8528879
TI  - Impairment of adrenocortical function associated with increased plasma tumor
      necrosis factor-alpha and interleukin-6 concentrations in African
      trypanosomiasis.
AB  - African sleeping sickness (SS) is a severe, potentially lethal parasitic disease.
      The treatments of choice are the antiparasitic agents suramin, which is
      adrenotoxic, and/or melarsoprol. We evaluated the functional integrity of the
      hypothalamic-pituitary-adrenal (HPA) axis of patients with SS before, during, and
      after therapy with suramin and/or melarsoprol, in two sequential stages. First,
      we employed the standard adrenocorticotropic hormone (ACTH) 1-24 stimulation test
      (250 micrograms i.v.) to assess the maximal adrenocortical responsiveness of 69
      patients with SS and 38 normal controls. We demonstrated paradoxically subnormal
      cortisol responses before suramin therapy [net cortisol response 60 min after
      stimulation: 10.5 +/- 2.9 (mean +/- SE) vs. 17.5 +/- 1.0 micrograms/dl for
      controls, p = 0.004], with 27% of the patients falling within the adrenal
      insufficiency range (stimulated cortisol concentration < 20 micrograms/dl). These
      responses subsequently and unexpectedly improved with suramin and/or melarsoprol
      therapy. Second, we performed a human corticotropin-releasing hormone (hCRH) test
      (100 micrograms i.v.) in 68 additional patients with SS and 14 control subjects
      to examine whether the glucocorticoid deficiency observed was primary and/or
      secondary. Compared to controls, the ACTH and cortisol responses to hCRH were
      blunted (ACTH after 60 min: 29 +/- 7 vs. 58 +/- 8 pg/ml in controls, p = 0.014;
      cortisol: 15.2 +/- 1.5 vs. 19.6 +/- 0.7 micrograms/dl, p = 0.018), suggesting the
      presence of secondary adrenal insufficiency. There was improvement of both ACTH
      and cortisol responsiveness to hCRH with therapy, with cortisol recovery
      occurring before ACTH, suggesting an additional primary component of adrenal
      dysfunction in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528880
TI  - Induction by cytokines of the pattern of pituitary hormone secretion in
      infection.

PMID- 8528881
TI  - Release of immunoreactive interleukin-1-alpha from rat hypothalamic explants is
      increased by bacterial lipopolysaccharide and high KCL concentrations.
AB  - It has previously been shown that interleukin (IL)-1-like bioactivity is released
      from rat hypothalamic explants in short-term incubations. Experiments conducted
      with antiserum against IL-1 alpha or IL-1 beta showed that IL-1 alpha is released
      more abundantly under basal conditions. For the present study, we developed a
      specific radioimmunoassay to investigate the release of immunoreactive (ir) IL-1
      alpha from the rat hypothalamus in short-term experiments, and observed that
      release of irIL-1 alpha increased with time and was significantly increased by
      high KCL concentrations. The stimulatory effect of 28 mM KCL was significantly
      inhibited by verapamil. Subsequent investigation of the effects of putative
      modulators of IL-1 alpha secretion, bacterial lipopolysaccharide (LPS) and the
      prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha), showed that irIL-1 alpha
      release was stimulated by 100 ng/ml LPS, but not by higher concentrations, PGE2
      had no effect and PGF2 alpha caused dose-dependent inhibition. However, the
      latter did not seem to exert a tonic inhibitory influence on irIL-1 alpha
      release, since blockade of cyclo-oxygenase activity by indomethacin had no effect
      on cytokine release under basal conditions. We conclude that LPS stimulates and
      PGF2 alpha inhibits basal release of hypothalamic IL-1 alpha, the characteristics
      of the secretion of which suggest that it may be, at least in part, of neuronal
      origin.

PMID- 8528882
TI  - The neuropeptide alpha-melanocyte-stimulating hormone inhibits experimental
      arthritis in rats.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) modulates inflammatory processes
      in models of acute inflammation and in models of sepsis/septic shock/adult
      respiratory-distress syndrome (ARDS). Because this neuropeptide inhibits actions
      of cytokines and other mediators of imflammation that are also believed to
      underlie aspects of chronic inflammation, tests were performed to compare the
      effects of repeated administration of the peptide with those of prednisolone and
      saline on the development of adjuvant arthritis in rats. alpha-MSH (50
      micrograms), injected i.p. twice daily, markedly inhibited the clinical and
      histological signs of experimental arthritis and moderated the weight loss
      observed in control animals. Prednisolone (100 mg/kg), given twice per day,
      prevented development of arthritis but caused marked and progressive weight loss.
      The results confirm the potent anti-inflammatory influence of alpha-MSH, in this
      case in a model of chronic inflammation that has immune components.

PMID- 8528883
TI  - Competitive reverse transcriptase-polymerase chain reaction using a synthetic
      internal RNA standard to quantitate transcripts for leukocyte-derived hormones.
AB  - Leukocytes synthesize a variety of hormones that were once thought to be unique
      products of endocrine tissues. Understanding the regulation of leukocyte-derived
      hormone synthesis requires an accurate means for measuring steady-state
      expression of specific mRNA transcripts. Here we describe a competitive reverse
      transcriptase-polymerase chain reaction (RT-PCR) technique to accurately
      quantitate macrophage-derived insulin-like growth factor-I (IGF-I) mRNA, and
      demonstrate the utility of this approach for measuring expression of leukocyte
      derived hormone transcripts. A riboprobe was constructed to generate
      approximately 1 kb of synthetic competitor IGF-I RNA (exons 1 and 3-6) that
      differed from cellular IGF-I RNA by insertion of 122 bp of beta-actin RNA. One
      set of oligonucleotide primers could thus be used to simultaneously reverse
      transcribe and amplify both 144 bp of cellular (exons 3 and 4) and 266 bp of
      competitor IGF-I RNA. Densitometric scanning of the PAGE-separated PCR products
      revealed that the ratio of competitor to cellular amplified DNA bore a linear
      relationship (r2 > or = 0.98) to the amount of competitor RNA for both rat liver
      and splenocytes. However, rat liver contained 104 x 10(6) IGF-I molecules per
      microgram of total cellular RNA compared to only 2 x 10(6) IGF-I molecules for
      splenocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528884
TI  - Plasma concentration of cytokine antagonists in patients with HIV infection.
AB  - There is increasing evidence that cytokines contribute to the immunopathogenesis
      of human immunodeficiency virus (HIV) infection. It may be, therefore, that
      compensatory rises in circulating cytokine antagonists also occur in HIV
      infection and that such changes mark disease progression. To test this idea,
      plasma concentrations of the cytokine antagonists alpha-melanocyte-stimulating
      hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and soluble
      tumor necrosis factor receptor (sTNFr) were measured in patients of different
      Centers for Disease Control (CDC) categories of HIV infection and in seronegative
      controls. Plasma levels of all these cytokine antagonists were higher in HIV
      infected patients. IL-1ra and sTNFr concentrations were correlated with
      indicators of disease activity: positively with plasma neopterin and negatively
      with CD4+ T lymphocyte counts. alpha-MSH and sTNF r were greater in CDC groups
      III and IV, whereas IL-1ra was elevated only in the latter group. Because
      cytokines activate the hypothalamic-pituitary-adrenal axis and adrenal steroids
      inhibit cytokine production, we measured circulating adrenocorticotropic hormone
      (ACTH) and cortisol in HIV-infected patients and investigated relations among
      these hormones, cytokine antagonists, and markers of disease progression. It
      appears that these physiological modulators of cytokine activity are not closely
      linked to sTNFr, IL-1ra and alpha-MSH: there were no significant correlations
      between plasma concentrations of ACTH or cortisol and those of cytokine
      antagonists, nor were there correlations between hormones and markers of disease
      progression such as neopterin or CD4+ T cell counts. It is notable that severe
      adrenal insufficiency was extremely rare (3%) in HIV-infected patients; it was
      confined to the AIDS group and was consistently secondary to ACTH
      deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528885
TI  - Effect of the administration of growth-hormone-producing lymphocytes on weight
      gain and immune function in dwarf mice.
AB  - Our previous work has shown that cells of the immune system produce a growth
      hormone (GH) molecule similar to that secreted by the pituitary. In the present
      studies, we evaluated the possibility that normal spleen cells producing GH
      transferred to dwarf mice could stimulate their growth. The results showed that
      normal spleen cells alone or spleen cells treated with growth-hormone-releasing
      hormone (GHRH) did not appear to significantly stimulate the growth of dwarf
      mice. Spleen cells activated in vitro with concanavalin A or lipopolysaccharide
      and then transferred to dwarf mice, or thymus cells alone, were also without
      effect, whereas GH alone stimulated growth as expected. Serum levels of insulin
      like growth factor-I (IGF-I) and IGF-I-liver RNA were undetectable in control
      dwarf mice and dwarf mice receiving spleen cells, whereas serum levels of IGF-I
      increased after treatment of dwarf mice with GH. The immune system of dwarf mice
      receiving spleen cells, however, was significantly altered. Spleen cells from
      dwarf animals showed enhanced immunoglobulin, interleukin (IL)-6, IL-2, and
      interferon-gamma production whereas no significant change was apparent in natural
      killer cell activity. Despite the absence of the pit-1 protein in dwarf mice,
      their spleen and thymus cells retained the ability to produce almost as much
      lymphocyte GH as normal. Overall, the findings support the idea that the pit-1
      protein in lymphocytes of dwarf mice may not be obligatory for the expression of
      lymphocyte GH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528886
TI  - 1,1'-Ethylidenebis[L-tryptophan], a contaminant implicated in L-tryptophan
      eosinophilia myalgia syndrome, suppresses mRNA expression of hypothalamic
      corticotropin-releasing hormone in Lewis (LEW/N) rat brain.
AB  - The L-tryptophan eosinophilia myalgia syndrome (L-Trp-EMS), related to ingestion
      of impure L-Trp, occurred in epidemic proportions in the United States in 1989.
      Epidemiologic studies implicated 1,1'-ethylidenebis[L-tryptophan] (EBT) as the
      impurity most highly associated with development of human L-Trp-EMS. We have
      previously shown that Lewis (LEW/N) rats fed L-Trp implicated in the L-Trp-EMS
      epidemic (case-associated L-Trp) develop fasciitis and perimyositis which is
      associated with a reduction in corticotropin-releasing hormone (CRH) mRNA
      expression in the hypothalamic paraventricular nucleus (PVN). In this study, we
      report the effects of EBT- and case-associated L-Trp on CRH mRNA expression in
      the hypothalamic PVN and secretion of adrenocorticotropic hormone (ACTH) and
      corticosterone (CORT) into the plasma over a time course of 1-6 weeks in the same
      rats in which we have found fascial thickening and immune cell activation induced
      by these compounds. Both control L-Trp and EBT stimulated the secretion of ACTH
      and CORT at 1-2 weeks, whereas case-associated L-Trp did not. EBT and case
      associated L-Trp decreased CRH mRNA expression in the PVN at 2-6 weeks, while
      control L-Trp had no effect. The striking contrast in the effects of case
      associated L-Trp and EBT on the HPA axis suggests that the reduction in CRH mRNA
      levels in the PVN seen in each case may be related to different mechanisms. It is
      possible that EBT suppresses CRH mRNA expression directly, in the absence of
      inflammation, while case-associated L-Trp may act through multiple mechanisms,
      including that associated with inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528887
TI  - Differential mineralocorticoid (type 1) and glucocorticoid (type 2) receptor
      expression in Lewis and Fischer rats.
AB  - Lewis (LEW/N) and Fischer (F344/N) rats represent two extremes of the spectrum of
      corticosterone responses to stressful stimuli, from the chronical
      hyporesponsiveness of LEW/N to the chronical hyperresponsiveness of F344/N. It
      might be expected that the amount of mineralocorticoid receptor (MR) and
      glucocorticoid receptor (GR) binding, and the levels of their corresponding mRNAs
      in various tissues in LEW/N and F344/N rats might reflect the overall integrated
      levels of corticosterone to which these receptors have been exposed. We have
      found that while the binding affinity (Kd) of MR and GR varies between tissues,
      there was no strain difference in any tissue. Receptor binding number (Bmax),
      however, varied not only between tissues, but also between strains. MR Bmax in
      the hippocampus and pituitary was lower in LEW/N than in F344/N, whereas the GR
      Bmax in the LEW/N thymus was greater than that found in F344/N rats. The
      hippocampal levels of MR mRNAs in Adx LEW/N and F344/N rats were in good
      agreement with, and paralleled, the functional levels of these receptors as
      determined by binding assays. On the other hand, the number of hippocampal GR
      binding sites and the level of GR nRNA while similar were not identical in the
      two strains: the hippocampal GR Bmax did not differ between strains, while the
      hippocampal GR mRNA level was slightly, but significantly, lower in Adx LEW/N
      compared to F344/N rats.

PMID- 8528888
TI  - Efferent signal(s) responsible for the conditioned augmentation of natural killer
      cell activity.
AB  - In in vivo studies, a conditioned increase in NK cell activity can be obtained by
      pairing odor of camphor (conditioned stimulus, CS) with poly I:C (unconditioned
      stimulus, US) in a single-association paradigm. We identified interferon (IFN) as
      the signal that reaches the central nervous system (CNS) to make an association
      with the camphor CS. We have also established that the CS/US association is an
      IFN-dependent step, and the expression stage is an opioid-dependent pathway which
      can be blocked with naltrexone and dexamethasone. Here we have focused on the
      signals responsible for the expression of conditioned augmentation of natural
      killer (NK) cell activity. The possible efferent signal molecules that were
      considered were IFN, beta-endorphin (beta-END), and adrenocorticotropic hormone
      (ACTH). Plasma levels of beta-END and ACTH of conditioned and control mice were
      quantitated by radioimmunoassay, and the changes in IFN message in the spleen
      cells were determined by Northern hybridization analysis. Results indicate that
      the ACTH levels and IFN-alpha gene expression were higher in the conditioned
      animals than in the controls. These studies support the view that ACTH released
      from the pituitary gland is involved in the up-regulation of IFN-alpha, which in
      turn stimulates the NK cells in the spleen.

PMID- 8528889
TI  - Cyclosporin A inhibits interleukin-2-induced release of corticotropin-releasing
      hormone.
AB  - Cyclosporin A (CSA), a potent immunosuppressive drug, has recently been shown to
      bind with high affinity to the immunophilin, cyclophilin. Calcineurin, the
      calcium-dependent protein phosphatase, binds the cyclophilin/CSA complex,
      rendering it inactive and blocking dephosphorylation of phosphoproteins. Very
      high concentrations of cyclophilin have been reported in the brain with a
      localization identical to that of calcineurin. We have reported that interleukin
      2 (IL-2) releases corticotropin-releasing hormone (CRH) by generation of nitric
      oxide (NO). Nitric oxide synthase (NOS), the enzyme in nitric oxidergic neurons
      that converts arginine into citrulline plus NO, is inactive in the phosphorylated
      state. We hypothesized that cyclosporin might therefore inhibit IL-2-induced
      acute CRH release by blocking the dephosphorylation of NOS by calcineurin.
      Consequently, we examined the effect of CSA on the release of CRH from mediobasal
      hypothalami (MBH) in vitro in 'basal' conditions and in the presence of IL-2,
      which we had previously shown to stimulate CRH release acutely in this
      preparation. Incubation of MBH for 30 min with IL-2 (10(-13) M), the
      concentration that was most effective in previous experiments, evoked a
      significant release of CRH. CSA at 10(-6) or 10(-8) M did not alter basal release
      of CRH; however, addition of either concentration completely blocked the IL-2
      induced release of CRH. This acute action of CSA within the brain is probably
      mediated by blockade of the dephosphorylation of NOS by calcineurin.

PMID- 8528890
TI  - Blockade by interleukin-1-alpha of nitricoxidergic control of luteinizing hormone
      releasing hormone release in vivo and in vitro.
AB  - Nitric oxide (NO) synthase (NOS), the enzyme that converts arginine into
      citrulline plus NO, the latter a highly active free radical, occurs in a large
      number of neurons in the brain, including certain neurons in the hypothalamus.
      Our previous experiments have shown that norepinephrine (NE)-induced
      prostaglandin E2 (PGE2) release from medial basal hypothalamic explants (MBH) is
      mediated by NO. Because release of luteinizing hormone (LH)-releasing hormone
      (LHRH) is also driven by NE and PGE2, we hypothesized that NO controls pulsatile
      release of LHRH in vivo, which in turn induces pulsatile LH release. Indeed, in
      vivo and in vitro experiments using an inhibitor of NOS (NG-monomethyl-L
      arginine; NMMA) demonstrated that pulsatile LH release is mediated by NO; LHRH
      release in vitro is also mediated by this free radical. Cytokines that are
      released from cells of the immune system during infection also inhibit LHRH
      release. We compared the action of one such cytokine, interleukin-1 alpha (IL-1
      alpha), on LHRH release with that of substances which inhibit or induce NO
      release. Microinjection of IL-1 alpha (0.06 pmol in 2 microliters) into the third
      cerebral ventricle (3V) of conscious, castrated male rats had an action similar
      to that of 3V microinjection of NMMA (1 mg in 5 microliters): it blocked
      pulsatile LH, but not follicle-stimulating hormone (FSH) release. The only
      difference between the responses to NMMA and IL-1 alpha was that the latency to
      onset was greater with IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528891
TI  - Local regulation of the immune response by the autonomic nervous system.
AB  - The autonomic innervation of the lymphoid tissue is currently visualized as a
      channel for neural regulation of immunity. Several reports have dealt with the
      alteration of antibody responses of spleen and lymph nodes following
      sympathectomy, and less often, parasympathectomy. This article reviews published
      data on the local effects of sympathetic and parasympathetic neurons innervating
      immunocompetent organs on immune responsiveness. A model comprising bilateral
      lymphoid organs (the submaxillary lymph nodes) and the local ipsilateral
      manipulation of their regional sympathetic nerves (derived from the superior
      cervical ganglia) and of their regional parasympathetic nerves (conveyed through
      the lingual nerve-chorda tympani) allowed the description of purely local effects
      of the autonomic nerves independent of the systemic effects of the surgical
      manipulation itself. By employing this model, the following were observed. (1)
      After the unilateral sympathetic denervation of murine submaxillary lymph nodes
      by superior cervical ganglionectomy (SCGx), ipsilateral increases in plate
      forming cell (PFC) activity, delayed hypersensitivity and graft-versus-host
      reactions were observed as compared to the contralateral, sham-operated,
      submaxillary lymph nodes. During degeneration of peripheral sympathetic nerves
      shortly after SCGx, PFC activity in ipsilateral submaxillary lymph nodes
      decreased significantly. (2) The local parasympathetic decentralization of murine
      submaxillary lymph nodes, achieved by the unilateral section of the chorda
      tympani, resulted in decreases of PFC activity, when challenged 10-20 days after
      denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528892
TI  - Type I glucocorticoid receptor blockade does not affect baseline or ovine
      corticotropin-releasing-hormone-stimulated adrenocorticotropic hormone and
      cortisol secretion.
AB  - The type I glucocorticoid receptor antagonist spironolactone was administered to
      healthy volunteers to determine the effect of type I receptor blockade on
      adrenocorticotropic hormone (ACTH) and cortisol secretion in humans. On separate
      days and in a double-blind, randomized fashion, placebo and each of four
      increasing doses of spironolactone were administered orally to subjects. Doses
      were selected to be within the clinically used range and, following drug
      administration, baseline and ovine-corticotropin releasing hormone (oCRH)
      stimulated ACTH and cortisol plasma levels were measured. In contrast to the
      clear effects of type II glucocorticoid receptor blockade on human pituitary
      adrenal function, no relationship between spironolactone dose or plasma levels
      and either basal or oCRH-stimulated pituitary-adrenal function was noted at doses
      comparable to those which induce type I receptor blockade and cardiovascular
      therapeutic effects in the kidney. These data suggest that, at physiologically
      relevant doses, type I glucocorticoid receptor blockade does not affect HPA axis
      function.

PMID- 8528893
TI  - Lidocaine interrupts the conditioned natural killer cell response by interfering
      with the conditioned stimulus.
AB  - In the present study, lidocaine, a local anesthetic that inhibits the initiation
      or conduction of nerve impulses, was used to differentiate between the memory for
      the conditioned stimulus (CS) and the memory for the CS and unconditioned
      stimulus (US) association. Lidocaine was used to block memory formation. It was
      administered into the cisterna magna to localize the inhibition to the central
      nervous system (CNS) where circuits for the CS and US exist. The results show
      that lidocaine specifically blocks the ability of the CS to stimulate the
      circuits responsible for storing the CS/US association, but it does not interfere
      with the inherent ability of the US to signal the CNS and trigger a peripheral
      response. The observation that the CS circuit can be interrupted independently of
      the US circuit suggests that these signals come together to form a new circuit
      for the memory of the association. The association memory forms later and is
      independent of the memory for the CS.

PMID- 8528894
TI  - Modification of cholinergic-mediated cellular transmembrane signals by the
      interaction of human chagasic IgG with cardiac muscarinic receptors.
AB  - The possible role of altered humoral immunity in cardiac Chagas' disease was
      examined by analyzing the interaction of IgG and the corresponding F(ab')2 from
      Trypanosoma cruzi-infected patients with cardiac muscarinic cholinergic receptors
      (mAchR). Human chagasic IgG and its F(ab')2 simulated the agonist actions
      triggering the biological effects associated with cholinergic-mediated cellular
      transmembrane signals, i.e. stimulation of cGMP, inhibition of cAMP and a
      decrease in atrial contractility. Atropine blunted all of these effects while
      pertussis toxin prevented the inhibition of cAMP and contractility confirming the
      G-regulatory-protein-mediated response in the interaction of chagasic antibodies
      with cardiac mAchR. In addition, chagasic IgG and its F(ab')2 behaved as partial
      agonists activating the specific receptor and inhibiting in a noncompetitive
      manner the activity of an exogenous agonist (pilocarpine). Moreover, chagasic IgG
      immunoprecipitated the mAchR solubilized from cardiac membrane in a concentration
      dependent fashion. By means of SDS-PAGE and immunoblotting analysis, chagasic
      serum was shown to recognize a band of approximately 75 kD. The electrophoretic
      studies of prelabeled immunoprecipitated proteins revealed a peak of [3H]
      propylbenzilylcholine mustard with an apparent molecular weight similar to that
      of mAchR, which disappeared in the presence of atropine. The presence of these
      antibodies in the serum of chagasic patients could explain the progressive
      receptor blockade in the parasympathetic branch of the cardiac autonomic nervous
      system associated with the cardioneuromyopathy described in the course of Chagas'
      disease.

PMID- 8528895
TI  - Chronic restraint enhances interleukin-1-beta release in the basal state and
      after an endotoxin challenge, independently of adrenocorticotropin and
      corticosterone release.
AB  - To explore the interactions between the hypothalamic-pituitary-adrenocortical
      axis and the immune system under stress conditions, we used an experimental rat
      model for chronic tail-restraint devised earlier for ground studies in space
      physiology. The system was used in two positions: (1) the orthostatic restraint
      position (OR) and (2) the antiorthostatic position (AOR) after the rat hind limbs
      had been raised by a head-down tilt. After 7 days of either restraint, sequential
      blood samples were taken via an indwelling aortic cannula, before and at various
      time intervals between 15 and 300 min after an intravascular infusion of 25
      micrograms/kg lipopolysaccharide (LPS). The plasma titers of adrenocorticotropin
      (ACTH), corticosterone (CORT) and interleukin-1 beta (IL-1 beta) were assayed.
      Under basal conditions, both OR and AOR restraints induced a 5-fold increase in
      IL-1 beta with no significant changes in ACTH and CORT levels. A robust increase
      in all three variables was observed after LPS injection. However, the IL-1 beta
      response to LPS was significantly higher in both restrained groups than in
      controls. Both the amplitude and the percentage of individually restrained rats
      displaying elevated IL-1 beta levels were increased up to 5 h. In contrast, the
      ACTH and CORT post-LPS responses were normal in the OR group. They were unusually
      dissociated in the AOR rats, which displayed depressed ACTH levels associated
      with slightly increased CORT levels. Our results suggest that immune
      neuroendocrine responses to chronic restraint stress may differ from those
      generally observed in acute stress.

PMID- 8528896
TI  - ACTH response to a low dose but not a high dose of bacterial endotoxin in rats is
      completely mediated by corticotropin-releasing hormone.
AB  - In experimental animals and humans, bacterial endotoxin activates the
      hypothalamus-pituitary-adrenal (HPA) axis. The pathways by which endotoxin
      stimulates adrenocorticotropic hormone (ACTH) and corticosterone secretion are
      uncertain. In the present study we compared the role of hypothalamic
      corticotropin-releasing hormone (CRH) in the activation of the HPA axis by a low
      (2.5 micrograms/kg) and a high (2.5 mg/kg) dose of bacterial endotoxin. Two
      experimental models were applied using chronically cannulated male Wistar rats.
      In the first model, rats were subjected to lesions of the hypothalamus that
      interrupted dorsal, lateral and frontal input to the median eminence
      (anterolateral deafferentation) or to sham operation and rats were used 7 days
      later. Before and at hourly intervals after endotoxin (2.5 micrograms/kg i.p.),
      blood samples were taken for the determination of plasma ACTH and corticosterone
      concentrations. Deafferentation of the hypothalamus strongly attenuated the
      elevations in plasma ACTH and corticosterone concentrations by a low dose of
      endotoxin compared to the responses in sham-operated animals. The second model
      involved passive immunization to CRH using a monoclonal antibody to rat/human CRH
      (PFU83). PFU83 (90 nmol/rat) abolished the elevation of plasma ACTH
      concentrations and attenuated corticosterone responses to a low dose of endotoxin
      (2.5 micrograms/kg i.p.) compared to that in control IgG-treated rats. Since the
      corticosterone responses to endotoxin were less effectively inhibited by the
      antibody than the ACTH responses, we postulate that non-ACTH-dependent mechanisms
      may contribute to the corticosterone response to endotoxin.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8528897
TI  - Effect of neonatal capsaicin on peptide-containing primary afferent fibres,
      eosinophil distribution and hyperresponsiveness in rat lung tissue following
      experimentally induced eosinophilia.
AB  - Treatment of neonatal rats with capsaicin causes a 92.4% loss of calcitonin-gene
      related-peptide-immunoreactive unmyelinated sensory afferent fibres in the
      airways epithelium, vascular smooth muscle and perivascular adventitial layer of
      lung tissue compared with vehicle-treated controls. Rats were administered
      Sephadex particles i.v. 8-10 weeks after either capsaicin or vehicle treatment at
      birth in order to induce a granulomatous tissue inflammation, peripheral blood
      eosinophilia and pulmonary eosinophil invasion [Laycock et al., Int Arch Allergy
      Appl Immunol 1986;81:363-367]. The animals also exhibited lung hyperreactivity in
      vitro in response to carbachol and serotonin (5HT). In Sephadex-treated rats,
      capsaicin pretreatment did not affect the number of inflammatory cells in
      peripheral blood, the number of eosinophils in lung tissue, or the distribution
      of eosinophils in the adventitial tissue of blood vessels. Potencies of
      concentration-related contractures of lung tissue to 5HT and carbachol were
      increased by 50- to 100-fold in Sephadex-treated animals compared to controls,
      but in neither group was potency influenced by capsaicin pretreatment at birth.
      Recruitment and subsequent regional distribution of inflammatory cells in lung
      tissue and the increase in lung hyperresponsiveness exhibited in this model of
      asthma do not appear to involve neuropeptides released from primary afferent
      neurones.

PMID- 8528898
TI  - Sex steroid regulation of the hypothalamo-pituitary-adrenal axis activity in
      middle-aged mice during endotoxic shock.
AB  - Many studies have documented the presence of a sexually dimorphic response of
      neuroendocrine functions in response to immune signals. The aims of the present
      study were to evaluate the hypothalamopituitary-adrenal (HPA) axis response to
      inflammatory stress stimulus in 15-month-old mice, and to determine whether such
      a response depends on circulating sex steroids. Our results indicate that in the
      15-month-old mice: (1) there is a sexual dimorphism in the HPA axis activity in
      basal condition and after endotoxin treatment with generally higher levels of
      several parameters of this axis in female than in male mice, (2) gonadectomy
      alone, followed by sex steroid therapy, modulates HPA axis function in both basal
      and stress conditions, and (3) whereas estradiol plays a stimulatory role on
      adrenal function, testosterone inhibits adrenal glucocorticoid production. This
      study further suggests a clear sexual dimorphism in middle-aged mice injected
      with endotoxin. These results may be relevant for the treatment of sepsis in aged
      patients.

PMID- 8528899
TI  - The anticytokine neuropeptide alpha-melanocyte-stimulating hormone in synovial
      fluid of patients with rheumatic diseases: comparisons with other anticytokine
      molecules.
AB  - The aim of this study was to determine if the anticytokine neuropeptide alpha
      melanocyte-stimulating hormone (alpha-MSH) occurs, along with interleukin 1
      receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFr),
      in synovial fluid of patients with rheumatoid arthritis (RA), juvenile chronic
      arthritis (JCA), or osteoarthritis. The data show that alpha-MSH does occur in
      the synovial fluid and its concentrations are greater in patients with RA than in
      those with osteoarthritis. Synovial fluid concentrations of IL-1ra and sTNFr were
      likewise greater in RA. Further, concentrations of alpha-MSH, IL-1-ra, and sTNFr
      were greater in patients with polyarticular/systemic-onset JCA than in those with
      pauciarticular disease, that is in patients with greater joint inflammation.
      Concentrations of alpha-MSH were greater in synovial fluid than in plasma in a
      substantial proportion of patients, suggesting local production of the peptide;
      this is the first indication that the anticytokine molecule alpha-MSH is produced
      within a site of inflammation. Further, it appears that local production of alpha
      MSH is induced particularly in those arthritic joints that have more intense
      inflammatory reactions. This finding, combined with previous evidence of the
      marked anti-inflammatory activity of alpha-MSH, suggests that the peptide acts
      locally to modulate proinflammatory influences in rheumatic diseases.

PMID- 8528900
TI  - Actin.

PMID- 8528901
TI  - Motor proteins. 1: kinesins.

PMID- 8528902
TI  - Transcription factors. 1: bZIP proteins.

PMID- 8528903
TI  - GTP-binding proteins. 1: heterotrimeric G proteins.

PMID- 8528904
TI  - Calcium-binding proteins. 1: EF-hands.

PMID- 8528905
TI  - Extracellular matrix. 1: fibril-forming collagens.

PMID- 8528906
TI  - Cell adhesion molecules. 1: immunoglobulin superfamily.

PMID- 8528907
TI  - Home-made excimer lasers are operating today in the US--the rest of the country
      watches and waits.

PMID- 8528908
TI  - FDA takes on maker of "homemade" excimer lasers.

PMID- 8528909
TI  - Custom excimer users threaten PRK success.

PMID- 8528910
TI  - Evaluating new refractive surgical procedures: free market madness versus
      regulatory rigor mortis.

PMID- 8528911
TI  - The challenge of corneal wound healing after excimer laser refractive corneal
      surgery.

PMID- 8528912
TI  - Classification of variable clinical response after photorefractive keratectomy
      for myopia.
AB  - BACKGROUND: Variation in healing response has been noted after excimer laser
      photorefractive keratectomy (PRK). METHODS: A retrospective analysis of 116 eyes
      that underwent PRK for myopia was performed. Standard surgical protocol and
      postoperative corticosteroid treatment were followed for all eyes. Scattergrams
      of achieved correction versus attempted correction at 6 months after surgery were
      analyzed. Subepithelial corneal haze was compared with refractive outcome.
      RESULTS: Three healing responses were observed. Normal responders (84.5%) showed
      a hyperopic overcorrection at 1 month with a gradual regression toward plano and
      good refractive outcome. Inadequate responders (11.2%) showed a pronounced early
      hyperopic overcorrection (greater than 1.50 diopters [D]) with minimal regression
      at 6 months. Aggressive responders (4.3%) displayed an early overcorrection with
      rapid regression toward myopia. Clear to trace subepithelial corneal haze was
      present at 6 months in 96% of normal and inadequate responders. Aggressive
      responders had more pronounced subepithelial haze at 6 months. CONCLUSION:
      Variation in the amount of subepithelial healing response occurs after excimer
      laser PRK. Abnormal healing responses may be detected early in the postoperative
      period by correlation of refractive error with the amount of subepithelial haze.

PMID- 8528913
TI  - Regional variation in corneal topography and wound healing following
      photorefractive keratectomy.
AB  - BACKGROUND: After excimer laser photorefractive keratectomy, corneal epithelial
      and anterior stromal wound healing may produce corneal haze and variability in
      refractive results among patients and eyes. METHODS: We report a retrospective
      study of 17 selected eyes that received excimer laser photorefractive keratectomy
      with one of three brands of laser and that exhibited regional variations in
      corneal wound healing as observed with slit-lamp microscopy and videokeratography
      (Tomey TMS) within the ablation zone. RESULTS: All 17 eyes were selected to show
      that the clear areas in the ablation zone corresponded with flat zones on the
      videokeratographs and the areas of subepithelial haze corresponded with steeper
      zones. Spectacle-corrected visual acuity was measured in 12 or the 17 eyes, and
      was 20/20 or better in 58% and 20/30 or better in 100%, indicating that the
      regional variation did not severely degrade Snellen visual acuity. Further
      studies are needed to determine how often regional variability occurs and to
      better define the relationship of corneal haze and corneal curvature. CONCLUSION:
      Regional variations in corneal topography and haze can occur within the ablation
      zone in an individual cornea after photorefractive keratectomy.

PMID- 8528914
TI  - Holmium laser thermal keratoplasty of 10 poorly sighted eyes.

PMID- 8528915
TI  - Intraocular pressure after excimer laser photorefractive keratectomy for myopia.

PMID- 8528916
TI  - Videokeratographic indices to aid in screening for keratoconus.

PMID- 8528917
TI  - Do topical corticosteroids have a role following excimer laser photorefractive
      keratectomy?
AB  - The article reviews the evidence for and against the use of topical
      corticosteroids following PRK. Two significant problems after PRK are the
      development of corneal haze and unpredictability of the refractive outcome. These
      arise from changes in the anterior stroma, the deposition of new subepithelial
      tissue, and individual variations in the wound healing response. In rabbits,
      corticosteroids reduced corneal haze by limiting the synthesis of subepithelial
      collagen. However, in humans, controlled trials showed that corticosteroids had
      no lasting effect on either haze or regression, and were associated with an
      unacceptably high incidence of unwanted effects. The difference between species
      probably related to the relative absence of collagen and predominance of
      glycosaminoglycans during corneal wound healing in humans. Some human studies
      have shown rapid changes in refraction occurring within days of stopping or
      restarting corticosteroids. This suggests that their transient hyperopic effect
      is probably mediated by changes in the hydration of the tissue. Therefore, the
      role of corticosteroids in PRK is very limited. There is no justification for
      their routine use after PRK for low or moderate myopia. If corticosteroids have a
      role in improving haze or refractive outcome in selected patients, a means for
      their early identification must be found.

PMID- 8528918
TI  - Phakic posterior chamber intraocular lenses for the correction of high myopia.

PMID- 8528919
TI  - Correction of myopia with Er:YAG laser fundamental mode photorefractive
      keratectomy.

PMID- 8528920
TI  - Comparison of histologic findings in wound healing of rabbit scleral homografts
      with fibrin glue (Tisseel) and suture material.

PMID- 8528921
TI  - [Pain and pain perception in the elderly].

PMID- 8528922
TI  - [Psychological diagnosis of pain and pain treatment in the elderly].
AB  - Chronic pain is one of the most common complaints in the elderly, associated with
      much impairment of quality of life. Up to now clinical research has focused
      little attention on pain in old age. Pain is often classified as an inevitable
      epiphenomena in the elderly. But present studies show that differences between
      older and younger patients appear less important than similarities. The studies
      also make evident that proved psychological pain management is transferable to
      elderly patients. The knowledge of effective psychological treatment in case of
      chronic pain in the elderly has been seldom realized in clinical practice.

PMID- 8528923
TI  - [Pain--from the physiological and internal medicine viewpoint].
AB  - Physiology of pain is a manifold and very complex phenomenon that is far from
      being understood. It cannot be explained without reference to psychosocial
      conditions. Pain has the function of a warning system, but the system is far from
      perfect, because a number of chronic diseases (e.g., arterial hypertension or
      malignant neoplasms) begin slowly and nearly painless. The role of pain in
      internal medicine will be exemplified by thoracic and abdominal pain. With regard
      to diagnoses both types of pain represent ambiguous symptoms. Their anatomic and
      physiologic substrates often cannot be ascertained completely by anamnestic means
      (according to localization, quality, trigger factors, time structure, and
      concomitant symptoms of pain). Visceral pain is regularly characterized by the
      phenomenon of the so-called "transferred pain": that means that the perception of
      pain is not restricted to the place of its origin but is also found in distant
      regions of the body, primarily in well defined dermatomes ("Head's areas"). This
      makes the differential diagnosis of internal diseases very difficult because of
      the parallel connection of nociceptive afferences from the skin and deeper-seated
      strata on identical spinal segments. Statements according to the
      pharmacotherapeutic aspects of pain primarily focus on the causal therapy of the
      prethoracic pain. In this regard differential-therapeutic aspects of angina
      pectoris, pericarditis, pleurisy, gastro-esophageal reflux, and vertebragenic,
      myogenic, and neurogenic disturbances are well to the fore.

PMID- 8528924
TI  - [Ambulatory pain treatment in tumor patients].
AB  - In this paper causes of pain and factors influencing sensitivity to pain in
      tumour patients are described. Changes and requests of outpatient therapy with
      non-opiates versus opiates are further analyzed. Results of pharmacological
      studies and clinical experiences show that most physicians have unjustified
      prejudice against prescription, effectiveness and side-effects of opiates. Some
      typical faults in outpatient therapy are a consequence of this kind of prejudice.
      An effective outpatient therapy using a phased plan in treatment with drugs could
      enable most tumour patients to become free of pain.

PMID- 8528925
TI  - [Pain and pain perception in the elderly from the viewpoint of rheumatology].
AB  - In rheumatology there is the problem of different terminologies and
      classification systems; additionally there are only few studies on differential
      diagnosis and course of diseases in people over 65. The analysis of pain is
      important for diagnosis; people often have problems in exactly describing their
      pains. The character of pain changes in the course of disease; therefore a
      continuous pain analysis is necessary.

PMID- 8528926
TI  - [Psychotherapy of somatoform pain disorders in the elderly].
AB  - This article focuses on somatoform pain disorders in elderly patients. Defined as
      a variant of the somatoform disorders, somatoform pain represents a disorder
      characterized by significant, physically experienced pain that is not (fully)
      explained by a medical condition. Although epidemiological data are sparse, the
      prevalence of somatoform pain disorders appears to decline with aging.
      Psychological factors are assumed to have an important role in the onset,
      severity, and maintenance of somatoform pain. In this article, two case reports
      are presented in order to illustrate the phenomenon that earlier pain
      experiences, e.g., in the context of a physical disorder or in the context of
      traumatic events, may "pave the way" for somatoform pain syndromes. Later acute
      mental stress or psychological conflicts may then precipitate the onset of
      somatoform pain. With respect to therapy, one should consider that patients with
      somatoform pain experience and interprete their suffering as a physical disorder.
      When applying psychotherapy to patients with somatoform pain disorders the
      therapist has to recognize and to appreciate eventual previous pain experiences
      which may have "paved the way" for the present disorder. Only after having
      established a therapeutic relationship can one try to interest the patient in the
      individual emotional and cognitive aspects that may underly the disorder. In
      addition to depressive feelings and feelings of guilt, grief about the loss of
      bodily functions may be of special significance for the onset and maintenance of
      somatoform pain disorders in elderly persons.

PMID- 8528927
TI  - [Psychosomatic aspects of pain perception by the elderly--results of the ELDERMEN
      Study].
AB  - 115 geriatric in-patients are included in the current study examining
      relationships between regions of experienced pain, subjective pain intensity, and
      psychological variables. An investigation of the connection between psychosomatic
      limitations (BSS) and pain indicated, that pain patients do not necessarily
      require psychosomatic-psychotherapeutic treatment (in our study only 21.6%).
      61.7% of the study sample reported intense pain at least one body region. These
      patients differed significantly from those with less pain in terms of their level
      of functional capacity and need for assistance in daily activities (ADL/IADL).
      They also displayed a significantly more negative attitude towards aging (PGC)
      than patients with minimal pain. Hierarchical cluster analyses for applied coping
      strategies produced five groups within the subgroup of patients suffering from
      extreme pain. Only within one group "depression" was a significant reaction to
      health-problems. These results make clear that most of the patients with extreme
      pain are able to cope effectively with pain.

PMID- 8528928
TI  - [Pain, independence and subjective attitude to aging--an empirical contribution
      from the study "Possibilities and limits of independent living by the elderly"].
AB  - In a study on chances and limits of independent life in old age, we collected
      data about sensations of pain in 990 participants. Information about intensity
      and frequency of pain sensations was combined to differentiate empirically
      between five patterns of pain sensations. According to severity, these patterns
      can be ordered hierarchically. 873 persons could be grouped into the five
      patterns of pain sensations. There was no relationship between chronological age
      and patterns of pain sensations. The relationship between patterns of pain
      sensations and degree of independence in everyday life was only weak. Comparing
      the five patterns of pain sensations in seven psychological variables, we found
      only few statistically significant differences, mainly between people who had no
      pain and those who suffered from strong or very strong pain most of the time or
      permanently. In KLC-measures of external and internal control beliefs related to
      health and body, in PGC-dimensions attitude towards age, lonely dissatisfaction
      and agitation as well as in PGC-score for life satisfaction, we found only few
      and weak differences between patterns of pain sensations. Stepwise multiple
      regression analysis with the independent variables degree of independence in
      everyday life, pattern of pain sensations and chronological age could explain
      1.4% to 6.7% of variance in those psychological variables. In contrast, patterns
      of pain sensations greatly differed in NAF-measures of subjective aging. A
      stepwise multiple regression with the independent variables degree of
      independence in everyday life and pattern of pain sensations could explain 24.6%
      of variance. Degree of independence in everyday life alone could explain 17.9% of
      variance. We hypothesize that effects in most psychological variables are weak,
      because what people mean by a "good" or personally satisfying life is only partly
      influenced by their health status.

PMID- 8528929
TI  - [Pain and psychological disorders in the elderly].
AB  - This paper points to different physiological diseases which are associated with
      extreme pain. Extreme and chronic pain can be related to a higher risk of
      suicide. Special patterns of pain are characterized psychologically. Furthermore,
      the relationship between pain and depression is discussed. The necessity for
      psychosomatic concepts in diagnosis and treatment of pain is shown. Special forms
      of experiencing pain in patients who suffer from dementia are described. These
      patients appear to have difficulties in perceiving and describing (clinical)
      pain.

PMID- 8528930
TI  - [Leisure interest activities within the context of mobility environments].
AB  - Selected activities of daily living are used to describe the micro-area
      (dwelling), mezzo-area (quarter) and exo-area (outside the quarter). In a survey
      of 115 elderly people, the five-year-changes from 1985/86 to 1990/91 in their
      areas of mobility in a working class district are documented. Special interest is
      given to the question, if people are making use of their areas by performing
      leisure activities. Social support is decisive for the access of areas which are
      limited by a person's physical status.

PMID- 8528931
TI  - [Genome analysis--burdens, rights and responsibilities for using genetic
      knowledge].

PMID- 8528932
TI  - [Interdisciplinary team--responsibilities and problems in the assessment of aging
      processes].

PMID- 8528933
TI  - Age-associated problems in nutrition.
AB  - From the chapters described so far, it is apparent that human beings may suffer
      many kinds of physiological declines during aging process. However, nutritional
      problems due to the physiological declines could be resolved by establishment of
      good eating patterns, intake of nutritionally balanced diet, appropriate nutrient
      supplementation of vitamins as well as minerals, and good nutrition program
      coupled with a regular exercise as mentioned in each chapters. Here is a Short
      Summary from the nutritional point of view for a longer, healthier, and more
      vital life. The balanced diet; especially the diet enhanced by vitamins E and B6
      and trace mineral zinc is helpful for the elderly to prevent the declines in the
      immune system. The foods rich in vitamin D and calcium; they may help to prevent
      the elderly from osteoporosis. The foods with low fat, dietary cholesterol and
      sodium; these foods may be recommended for not only the elderly but also younger
      people to reduce the risk of cardiovascular disease. The good quality of diet; it
      is important for the elderly to avoid the monotonous diet because of their
      appetite declines.

PMID- 8528934
TI  - Circulatory regulation during supine and sitting intermittent isometric handgrip
      in a hot environment.
AB  - We studied the circulatory regulation during intermittent isometric handgrip
      (IIHG, six seconds contraction + six seconds relaxation) in supine and sitting
      postures in a hot environment (40 degrees C, RH: 50%). Eight healthy male
      subjects performed thrice 5-minute period IIHG at three different work loads
      (10%, 20% and 30% MVC). The IIHG was performed with the right hand in the two
      postures. Heart rate (HR), cardiac output (CO), mean arterial blood pressure
      (MBP), forearm blood flow (FBF), skin blood flow (SBF), foot swelling (FSW) and
      tympanic temperature (Tty) were measured during IIHG, resting and recovery
      periods. During IIHG in a hot environment, HR, MBP, FSW and Tty showed higher
      values in the sitting than in the supine posture. FBF during relaxation showed
      higher values at high work load than at low work load in the two postures. FBF
      showed higher values in the sitting than in the supine posture, except during
      relaxation at 30% MVC. It was concluded that the decrements of blood volume of
      splanchnic organs might be greater in the sitting than in the supine posture due
      to sympathetic vasoconstrictor activity, and were responsible for the
      redistribution of blood flow. Posture had an effect on FBF because of hydrostatic
      pressure.

PMID- 8528935
TI  - A study on the difference of human sensation evaluation to whole-body vibration
      in sitting and lying postures.
AB  - The evaluation of vibration sensation is a problem which has large individual
      differences. In order to clarify the relationship between posture and
      psychological response, human sensation to whole-body vibration (from 2 to 11 Hz)
      in sitting and lying postures was evaluated by the semantic differential method,
      and the influences of posture on the evaluation were investigated by using the
      fuzzy measure. Furthermore, the paired t-test was used to test the significant
      differences in the results of evaluation between the two postures. The results
      were as follows: (1) Psychological responses of human beings to whole-body
      vibration were greatly affected by the postures. (2) Changes of the psychological
      responses in the lying posture were smaller than those in the sitting posture.
      (3) There were significant differences between sitting and lying postures in the
      evaluation results of physiological factor, psychological factor and synthetic
      evaluation (P < 0.025).

PMID- 8528936
TI  - Changes in body shape of young individuals from the aspect of adult physique
      model by factor analysis.
AB  - The purpose of this study was to clarify characteristics of age-related changes
      in body shape in adolescence, in 11- to 19-year-old boys and girls, by using
      previously reported physique models of adult men and women as the scale. The
      scale consisted of four factors obtained by factor analysis using 30 items as
      variables, such as the values measured for the physique, skinfold thickness and
      body composition. The four factors were Factor 1: body fat, Factor 2: mass,
      Factor 3: leg length to height ratio, and Factor 4: length, and were interpreted
      in the men and women in a similar manner. The subjects were 307 boys and 368
      girls; all were healthy. Thirty items were measured and included the values
      measured for the physique, skinfold thickness and body composition, as in the men
      and women. Factor scores in the subjects were standardized by mean and standard
      deviation for each item in the adult subjects, and calculated for individuals by
      using the coefficient of factor score in the adult subjects. The body shapes of
      the boys and girls were investigated from the factor score by age calculated for
      each factor. The following results were obtained: 1. Factor 1 tended to gradually
      decrease and reached the adult level at 15 years of age in the boys.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8528937
TI  - Physiological and subjective responses to standing showers, sitting showers, and
      sink baths.
AB  - The purpose of this study was to investigate physiological and subjective
      responses during and after bathing in three different bathing methods. Eight
      healthy males bathed for 10 minutes, and then rested for 30 minutes. Three kinds
      of bathing methods - standing shower, sitting shower and sink bath - were adopted
      in this experiment. Water temperature and flow volume of the showers were kept at
      41 degrees C and 11 liter/min, while water temperature of the bath was kept at 40
      degrees C. Rectal temperature, skin temperatures and heart rate of the subjects
      were measured continuously during bathing and the subsequent 30-minute rest.
      Blood pressure and votes for thermal sensations were recorded before bathing,
      after 5 and 10 minutes of bathing, and 5, 10, 20 and 30 minutes after bathing.
      The following results were obtained. 1) Although rectal temperature rose, on the
      average, by 0.15 degrees C in all bathing methods, there were no significant
      differences among the three bathing methods at any time in the experiment. 2)
      Mean skin temperature (Tsk) during the sink bath was significantly higher than
      that in the standing or sitting shower. After bathing, Tsk of sink bath was
      slightly higher than those of the remaining conditions, but did not significantly
      differ among the bathing methods. 3) Heart rate increased gradually during all
      the bathing methods, however, only HR in the standing shower exceeded 100
      beats/min which was significantly higher than those of the two remaining bathing
      methods. 4) Blood pressure (BP) decreased rapidly during the sink bath in
      contrast to an increased BP in the sitting and standing showers.

PMID- 8528938
TI  - Interferon-alpha inhibits erythropoietin-induced proliferation, but not
      differentiation, and restricts erythroleukemia development.
AB  - The immature erythroid cell line J2E responds to erythropoietin (Epo) by
      proliferating and terminally differentiating into hemoglobin-synthesizing red
      blood cells. These cells produce a rapid, fatal erythroleukemia in mice
      characterized by hepatosplenomegaly and severe anemia. The aim of this study was
      to investigate the effects of murine interferons-alpha (MuIFN-alpha) on J2E cells
      in vitro and in vivo. Here we show that in culture MuIFN-alpha inhibited the Epo
      induced proliferation of J2E cells but did not interfere with differentiation.
      When mice with J2E erythroleukemias were treated with MuIFNs in vivo, an
      extension of their life span was observed. Moreover, numerous necrotic lesions of
      infiltrating leukemic cells were detected in the spleens of these mice. Finally,
      ex vivo treatment of leukemic bone marrow cells with Epo and MuIFNs delayed
      mortality even further. It was concluded that MuIFNs (1) suppressed the
      proliferation of J2E cells in vitro but did not affect Epo-induced
      differentiation, and (2) inhibited the progress of erythroleukemias, especially
      in combination with Epo.

PMID- 8528939
TI  - Novel mutein of tumor necrosis factor alpha (F4614) with reduced hypotensive
      effect.
AB  - To eliminate systemic toxicity, including the hypotension associated with human
      tumor necrosis factor alpha (TNF-alpha), we constructed mutant proteins (muteins)
      by mean of genetic engineering. A novel mutein, F4614, containing mutations of
      5Thr-->Gly and 6Pro-->Asp, which resulted in the introduction of cell-adhesive
      Arg-Gly-Asp and 29Arg-->Val, had remarkably reduced hypotensive effects and lower
      lethality. We present evidence that the Arg-->Val mutation at position 29 is
      largely responsible for the reduced hypotensive effect. This effect of F4614 was
      thought to be closely correlated with its low inducibility of nitric oxide and
      prostaglandin E2 in vivo. In addition, the therapeutically effective dose of
      F4614 to MethA fibrosarcoma-transplanted mice was increased compared with that of
      TNF-alpha, indicating a wide therapeutic index. These results indicated that
      F4614 has several advantages as a systemic therapeutic drug in the treatment of
      cancer.

PMID- 8528940
TI  - Transforming growth factor beta 1 inhibits interleukin-10 mRNA expression and
      production in pokeweed mitogen-stimulated peripheral blood mononuclear cells and
      T cells.
AB  - The multifunctional cytokine transforming growth factor-beta 1 (TGF-beta 1) is
      known to inhibit the proliferation of lymphocytes. Whether this effect is a
      result of a direct action of TGF-beta 1 or an involvement of other
      "immunoinhibitory" cytokines is not yet clear. Here we have analyzed the effects
      of TGF-beta 1 on IL-10 and IL-1RA production in pokeweed mitogen-stimulated
      peripheral blood mononuclear cells (PBMC) and purified T lymphocytes. We show in
      these systems that TGF-beta 1 at a concentration of 10 ng/ml significantly
      suppresses both IL-10 mRNA expression and IL-10 production. IL-2 and IL-6 were
      capable of abolishing the effect of TGF-beta 1 on DNA synthesis and production of
      IL-10 by T lymphocytes in an additive manner. However, TGF-beta 1 did not
      influence IL-1RA production in PWM-stimulated PBMC. The present data show that
      the inhibitory effect of TGF-beta 1 on mitogen-activated immune cells is not the
      consequence of induction of the inhibitory cytokines IL-10 or IL-1RA but rather
      an inhibitory action on the production of IL-2 and/or IL-6.

PMID- 8528941
TI  - Characterization of a rainbow trout Mx gene.
AB  - A full-length cDNA clone of a rainbow trout (Oncorhynchus mykiss) Mx gene was
      obtained using RACE (rapid amplification of cDNA ends) polymerase chain reaction
      (PCR) amplification of RNA extracted from poly (I).(C)-induced rainbow trout
      gonad cells (RTG-2). Mx was previously identified in rainbow trout by Staeheli et
      al. by hybridization with a partial perch genomic Mx probe to induced rainbow
      trout mRNA. The 2.5 kb rainbow trout cDNA clone contains an open reading frame of
      1863 nt (nucleotides) encoding a 621 amino acid protein. The deduced rainbow
      trout Mx protein is 70.6 kD and contains the characteristic tripartite GTP
      binding motif common to all Mx protein. Southern blot analysis with the rainbow
      trout Mx probe demonstrated the presence of Mx homologous genes in four other
      salmonid fish species, including chinook, coho, and kokanee salmon and brook
      trout. Poly (I).(C) treatment of both RTG-2 and chinook salmon cells (CHSE-214)
      induced two transcripts whose appearance was observed first at 24 h and as long
      as 72 h after treatment. Infection of rainbow trout with the salmonid
      rhabdovirus, IHNV (infectious hematopoietic necrosis virus), also induced the
      synthesis of Mx mRNA. A comparison of the rainbow trout Mx protein with other
      reported Mx proteins indicates that the piscine Mx is highly homologous to the
      mammalian Mx proteins.

PMID- 8528942
TI  - Serum lipid levels during interferon therapy in patients with chronic hepatitis
      C.
AB  - Interferon-alpha (IFN-alpha) may affect lipid metabolism by stimulating hepatic
      fatty acid synthesis. The aim of this study was to evaluate serum lipid levels
      during IFN-alpha therapy in patients with biopsy-proven chronic active hepatitis
      C. A total of 22 patients (18 males and 4 females; age 25-55 years) received 3 MU
      of recombinant IFN-alpha 2b 3 times a week for 6 months. Serum lipids were
      determined at baseline and then every month until the end of therapy. All
      patients had normal serum lipid levels at baseline. No significant level of
      modification occurred in patients during the therapy. An increase in serum lipid
      levels during low-dose IFN-alpha therapy seems to be uncommon in hepatitis C
      virus-infected patients with baseline normal levels.

PMID- 8528943
TI  - Changes in blood lipid composition and response to interferon treatment in
      chronic hepatitis C.
AB  - To assess whether the initial status of lipid metabolism in patients with chronic
      viral hepatitis might correlate with outcome of therapy, 52 patients (32 males
      and 20 female) with chronic hepatitis C were studied: 44 were treated with human
      recombinant interferon-alpha 2b (3 MU three times per week for up to 12 months),
      and 8 served as controls. At baseline, sera were tested for total and HDL
      cholesterol, HDL2, HDL3, apolipoprotein A-I, apolipoprotein B, interferon-alpha,
      tumor necrosis factor, and interleukin-6. Changes in blood lipids were evaluated
      after 3, 30, and 90 days of treatment. HDL cholesterol, apolipoprotein A-I, and
      HDL3 decreased by 9.4-11.4% within 4 weeks of starting interferon treatment, but
      this effect was sustained only in patients with a primary response to interferon.
      On multivariate analysis, a primary response to interferon correlated with higher
      apolipoprotein A-I and lower (< 2.23 pg/ml) interleukin-6 levels (p < 0.005 for
      both). In contrast, a sustained response was significantly more common in
      patients with low (< or = 13.3 pg/ml) serum interferon-alpha and lower
      interleukin-6 at baseline but did not correlate with any of the blood lipids.
      Thus, in chronic hepatitis C, interferon treatment induces specific changes in
      blood lipids. The concentration of apolipoprotein A-I at baseline is a strong
      predictor of primary response to treatment, and the likelihood of sustained
      response seems to be reflected by lower cytokine activation.

PMID- 8528944
TI  - Glycosylated human recombinant interleukin-1 alpha, neo interleukin-1 alpha, with
      D-mannose dimer exhibits selective activities in vivo.
AB  - To investigate the effect of carbohydrate-introduction on IL-1 activity,
      especially in vivo, and to develop IL-1 with less deleterious effects,
      recombinant human IL-1 alpha was coupled with mannose dimer, alpha-D-Man-1-6-D
      Man [Man2 alpha(1-6)] by an acyl azide method. Previous studies demonstrated that
      the glycosylated IL-1 exhibited reduced activities compared with original IL-1 in
      all the experiments performed in vitro. In this study, we investigated the in
      vivo activities of Man2 alpha(1-6)-conjugated IL-1 alpha. The glycosylated IL-1
      alpha exhibited very low pyrogenic activity and alpha 1-acid glycoprotein
      induction compared with untreated IL-1 alpha. Untreated IL-1 alpha increased the
      serum level of IL-6, but the glycosylated IL-1 alpha did not. However, the
      glycosylated IL-1 alpha possessed the same potency as untreated IL-1 alpha in
      reduction of serum levels of glucose and triglyceride and in recovery of
      peripheral white blood cells in 5-fluorouracil-treated mice. Therefore,
      glycosylation of IL-1 appeared to be useful for the development of neoIL-1 with
      selective activity in vivo.

PMID- 8528945
TI  - Interleukin-1 receptor antagonist protein and mRNA in the rat adrenal gland.
AB  - The occurrence of the endogenous receptor antagonist for the cytokine interleukin
      1 in the rat adrenal gland was analyzed y polymerase chain reaction and by
      immunohistochemistry using a rabbit polyclonal antiserum. Expression of
      interleukin-1 receptor antagonist mRNA was demonstrated in both adrenal medulla
      and cortex, and a marked increase in the transcription was observed after
      systemic administration of lipopolysaccharides. Interleukin-1 receptor antagonist
      immunoreactivity was seen in the adrenal medulla, and the immunofluorescence
      intensity was stronger in the adrenergic, phenylethanolamine N-methyltransferase
      positive cells than in the noradrenergic chromaffin cells. The distribution of
      interleukin-1 receptor antagonist protein is complementary to that of interleukin
      1 alpha-like immunoreactivity found in phenylethanolamine N-methyltransferase
      negative cells and overlaps with and resembles the distribution of interleukin-1
      beta-immunoreactive material. The expression of the interleukin-1 receptor
      antagonist in the adrenal gland complements previous findings of large
      constitutive pools of interleukin-1 alpha and interleukin-1 beta in this
      neuroendocrine organ and also suggests participation of adrenal interleukin-1
      receptor antagonist in neuroimmune modulation.

PMID- 8528946
TI  - Prothymosin alpha receptors on lymphocytes.
AB  - Recent results indicate that prothymosin alpha (ProT alpha) may be useful in
      designing future therapeutic interventions in cancer patients and in potentiating
      the immune system. We described recently the presence and characteristics of two
      binding sites for ProT alpha on human peripheral blood mononuclear cells (PBMC).
      In search of a receptor upregulation, we decided to corroborate this finding on
      two lymphocytic populations, (PHA-activated) lymphoblasts and YT cells. The
      kinetics of [125I]ProT alpha binding to lymphoblasts were fast at room
      temperature but with YT cells were slower. Analysis of steady-state binding data
      identified two binding sites in lymphoblasts with an apparent equilibrium Kd of
      44-75 pM and 4228-9143 sites per cell for the high-affinity receptor and 1.7-2.9
      nM and 20,534-35,044 sites per cell for the low-affinity receptor. However, it
      identified only one site with a Kd of 265-435 pM and 8318-27,237 sites per cell
      in YT cells. We conclude that exists a ProT alpha receptor in the CD3+ T cell
      population, and this presence is regulated. After binding to cell surface,
      [125I]ProT alpha is internalized in a short period of time and then degraded;
      therefore, we conclude that the dynamics of ProT alpha receptor turnover in part
      determines the concentration of ProT alpha available to induce its enhancing
      effects.

PMID- 8528947
TI  - Analysis of cytokine secretion by melanoma-specific CD4+ T lymphocytes.
AB  - Although specific antitumor immune reactivity has been documented extensively in
      CD8+ T cells derived from melanoma patients, relatively little is known about
      CD4+ T cell responses against melanoma. Tumor-infiltrating lymphocytes (TIL)
      cultured from metastatic lesions in five patients yielded cytolytic CD8+ T cells
      with specific activity against autologous and MHC class I-compatible allogeneic
      melanoma targets. In four of the five cases studied, CD4+ T cells purified from
      bulk TIL cultures also reacted specifically with autologous melanoma cells, as
      manifested by the secretion of various cytokines (GM-CSF, TNF-alpha, and IFN
      gamma) after a 24 h cocultivation. Cytokine secretion by CD4+ T cells was MHC
      class II restricted, and proved to be a more reliable indicator of the
      immunologic reactivity of CD4+ T cells than cytolysis. Three of the four reactive
      CD4+ TIL failed to recognize allogeneic melanomas, suggesting recognition of Ag
      with limited expression in the patient population. Cloning such Ags may provide
      clues to optimizing current antitumor immunization strategies.

PMID- 8528948
TI  - [A review of studies of the delayed neurotoxicity induced by organophosphorus
      esters].
AB  - Organophosphorus esters have been used in the plastics industry as antioxidants
      and plasticizers, in agriculture as insecticides, and in the military as nerve
      agents. Some of these compounds have organophosphorus ester-induced delayed
      neurotoxicity (OPIDN) different from the acute toxicity caused by the
      acetylcholine esterase inhibiting activity. this review describes recent progress
      in studies on OPIDN and, discusses the future direction of studies. OPIDN is
      characterized by a more than 7 day incubation period, lower limb paralysis
      accompanied by axonal degeneration, and age- and species-specificity. Younger
      animals and rodents are not very sensitive to OPIDN. As well as fast recovery of
      inhibited neurotoxic esterase or neuropathy target esterase (NTE) in the sciatic
      nerve, detoxicating mechanisms including carboxylesterases are contributing to
      age- and species-specificity for OPIDN. Although, anterograde axonal transport
      does not seem to be affected by OPIDN, slow down of retrograde axonal transport
      was observed. Inhibition of NTE, and aging of inhibited NTE has been thought to
      be responsible for OPIDN, but there are some arguments against the role of NTE in
      OPIDN. Phosphorylation of cytoskeletal proteins by kinases such as calcium
      dependent-calmodulin kinase II and/or high affinity neurotoxic compound binding
      site(s) are possible candidates for the initiation of OPIDN. Triphenyl phophite
      (TPP), a compound commonly used in the plastics industry, has delayed
      neurotoxicity that is somewhat different from OPIDN. The onset of TPP-induced
      neuropathy is earlier than that of OPIDN, and rodents are sensitive to TPP. In
      addition to the axonal damage, cell damage is observed in TPP-induced neuropathy.
      Mitochondrial energy metabolism-related enzymes could be the target of this
      neuropathy. Future studies should be focused on the relation of OPIDN to the
      phosphorylation of cytoskeletal proteins and high affinity binding site(s), and
      on the development of rodent models. These studies would answer the questions
      related to OPIDN, and further contribute toward elucidating the pathogenesis of
      degenerative neuronal diseases.

PMID- 8528949
TI  - [Computed tomography of pneumoconiosis].
AB  - This review describes the usefulness of computed tomography (CT) and high
      resolution computed tomography (HRCT) in image evaluation in pneumoconiosis. For
      pneumoconiosis, in the same way as for other diffuse lung diseases, conventional
      CT includes 10 mm collimation scans at 1 cm intervals from the apex to the base
      of the lung, whereas HRCT uses five to six 1.2 to 3 mm collimation scans at
      predetermined representative locations including the aortic arch, the tracheal
      carina, and 2 cm above the dome of the right hemidiaphragm. The CT scans are
      performed in the supine position in silicosis and coal workers' pneumoconiosis,
      and both in the supine and prone position in asbestosis. In silicosis, CT is
      superior to chest radiography in detecting coalescence of nodules and early stage
      formation of large opacities. There are good correlations between HRCT findings
      and histological changes, especially in secondary pulmonary lobules. With HRCT,
      small nodules are found to be located in the center of the secondary pulmonary
      lobule in silicotic lungs. The mild emphysematous change associated with
      silicosis can also be found with HRCT. In coal workers' pneumoconiosis, the HRCT
      is useful in detecting nodules located in the subpleural and fissural subpleural
      areas. In asbestosis, the conventional CT can detect pleural plaques more
      sensitively than chest radiography. HRCT is also especially useful in detecting
      earlier fibrotic change in asbestosis in lung parenchyma, apparent as subpleural
      lines, parenchymal bands, subpleural curvilinear line shadows and so on.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8528950
TI  - [The relationship between work factors and psychiatric symptoms--a comparison
      between anxiety and depression].
AB  - The depression scale (Zung Self-rating Depression Scale) and the anxiety scale
      (State-Trait Anxiety Inventory) have often been used to study the mental health
      of workers. We carried out a comparative study to determine which these two
      scales more clearly reflects the work stress. We used two methodologically
      different materials: a questionnaire survey and mental health consultation
      records. The questionnaire was sent to 885 male workers in a large industrial
      company and its related companies, and the consultation cases were 84 male
      workers coming from the area where the questionnaire survey was conducted. The
      work problem questionnaire was factored and the four work factors that were
      obtained were used in the succeeding analyses. The results of the questionnaire
      survey showed that depression had a higher multiple correlation with the four
      work factors than did the state anxiety. Similarly, the consultation cases, in
      which the main symptom was depression, accounted for a little more than 40% of
      all cases, but the anxiety cases accounted for only 10%-20%. Both studies
      indicated that depression is a more important manifestation of work stress than
      anxiety. The questionnaire survey also showed that the "quality-of-work" factor
      and the "work-quantity/environment" factor had relatively high standardized
      partial regression coefficients, when depression was predicted by the four work
      factors. In the case of the consultation cases, more than 50% of the depressive
      cases were caused by overload. Since the "work-quantity/environment" factor was
      considered to be closely related to overload, the salient relation between
      depression and overload agrees with the results of the consultation
      research.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528951
TI  - [Study on personal variance of laboratory data from long-term observation].

PMID- 8528952
TI  - [Bronchopulmonary dysplasia and inflammation].

PMID- 8528953
TI  - [Pathogenesis of bronchopulmonary dysplasia].
AB  - Bronchopulmonary dysplasia of preterm infants has a multifactorial etiology.
      Pulmonary immaturity, oxygen toxicity, formation of oxygen radicals and
      mechanical lung trauma as well as additional factors (pulmonary hyperhydration,
      infection a.o.) may contribute to pulmonary damage. A pulmonary inflammatory
      reaction is thought to play a central role in the pathogenesis of chronic lung
      disease. It is characterized by the presence of inflammatory cells and various
      inflammatory mediators including proteases, chemoattractants, cytokines,
      leukotrienes and others. Due to the immaturity of several protective systems
      (antiproteases, antioxidants, surfactant system) the inflammatory response seems
      to be aggravated. Moreover, the magnitude and persistence of inflammation may
      eventually lead to pulmonary fibrosis.

PMID- 8528954
TI  - [Severe protracted intrauterine impaired perfusion--a cause of enteral motility
      disorder in the premature infant].
AB  - The importance of measurement of blood flow in the fetal and uteroplacental
      circulations for the assessment of fetal wellbeing has been undisputed since some
      years. The present study is designed to prove if any relationship exists between
      severe hemodynamic disturbance in fetal as well as uteroplacental vessels and the
      occurrence of postnatal impairment of intestinal motility. The progress of 130
      children, born in the University Women's Hospital Leipzig between 1991-1993 and
      with birth weights below 1500 g, has been analyzed. Doppler ultrasound
      examinations for detection of impairment in fetal and uteroplacental circulation
      were performed in all cases during pregnancy. A severe impairment of blood flow
      in the above mentioned circulations was defined by the presence of pathological
      pulsatility or resistance indices in both fetal and uteroplacental vessels as
      well as absent end diastolic flow in the umbilical artery and signs of
      centralization in the fetus. A severe hemodynamic impairment was found in 27
      children and 26 of these were classified as severe hypotrophic after birth. The
      progress of these children was compared with this of other hypotrophic and
      euthrophic premature babies who had not revealed hemodynamic abnormalities. The
      incidence of disturbed postnatal intestinal motility (delayed meconium excretion,
      abdominal distention, retrograde peristalsis, subileus) was significantly higher
      in hypotrophic neonates with hemodynamic abnormalities in the course of
      pregnancy. Four of these newborns underwent surgery and surgical findings did not
      correlate with enterocolitis. The resumption of oral food intake for neonates who
      had hemodynamic impairments during pregnancy was delayed compared with the
      control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528955
TI  - [Normal pregnancy duration after maternal Fontan operation of univentricular
      heart].
AB  - Up to now pregnancy in patients with a previous Fontan operation for definitive
      palliation of a univentricular heart has been regarded as contraindicated. Two
      cases of a pregnancy after Fontan operation and univentricular heart were
      published in the literature. In a single case a successful delivery of the fetus
      could be achieved. The presented case is the third published pregnancy after
      Fontal operation and the second with a successful fetal outcome. The 30 years old
      patient was born with a univentricular heart of right ventricular type with
      tricuspid and pulmonary atresia and persisting arterial duct. After bilateral
      Blalock Taussig anastomoses (1966) and modified Waterston-Cooley-anastomosis
      (1974) a primary existing cyanosis could be improved. The cyanosis was completely
      abolished after definitive repair with the Fontan operation at the age of 17
      (1980). The course of pregnancy and its surveillance is reported. In the 32nd
      week of gestation cesarean section had to be performed because of threatening
      cava compression. A healthy female fetus of 1275 g was delivered. The mother's
      postoperative recovery was uneventful. Meanwhile the neonate and the mother have
      been discharged and are in good clinical condition.

PMID- 8528956
TI  - [First aid and resuscitation of newborn infants--techniques, indications and
      risks].

PMID- 8528957
TI  - [Obstetrical delivery of small premature infants--are there legal guidelines?].

PMID- 8528958
TI  - [21st Meeting of the German-Austrian Society for Neonatology and Pediatric
      Intensive Medicine. Mannheim, 26-28 October 1995. Abstracts].

PMID- 8528959
TI  - Expression of a tumor-reactive antibody-interleukin 2 fusion protein after in
      vivo particle-mediated gene delivery.
AB  - We have used a particle-mediated gene transfer method to analyze the
      posttransfection expression pattern of an antibody-cytokine fusion protein (FP)
      in vivo. The FP, denoted CC49-IL2, consists of a single-chain antibody containing
      the antigen recognition domain from the murine monoclonal antibody CC49
      (recognizing the tumor-associated antigen TAG-72), a human IgG1 constant heavy
      chain, and human interleukin-2 (IL-2). This FP can bind to TAG-72-expressing
      tumor cells and exhibits IL-2 activity. To induce systemic levels of this FP in
      vivo, we have transferred the FP gene into murine epidermal cells by direct
      delivery of DNA-coated gold particles using a transcutaneous "gene gun." After
      the pericutaneous delivery of the FP gene via gold particles, production of the
      exogenous FP was detected at the epidermal target site. The FP produced in vivo
      at the site of gene delivery has cytokine activity and antigen recognition
      capabilities similar to those present in CC49-IL2 FP purified from hybridoma
      culture supernatants in vitro. FP was also detectable in the serum from test
      animals treated with particle-mediated gene transfer. Time course experiments
      indicated that serum levels of FP reached a peak level within 8 hours after DNA
      delivery, whereas the epidermal target tissue levels continued to increase for 24
      hours before plateauing. Our results indicate that exogenous protein levels
      consistent with immunotherapeutic effects of the FP can be readily achieved at
      the skin tissue site of gene delivery, with the potential for achieving
      therapeutic levels systemically.

PMID- 8528960
TI  - Sustained cytokine production and immunophenotypic changes in human neuroblastoma
      cell lines transduced with a human gamma interferon vector.
AB  - The majority of human neuroblastomas express low to undetectable levels of major
      histocompatibility complex (MHC) class I and II antigens (MHC-I and -II). We
      studied the effects of gamma interferon (gamma-IFN) transduction on expression of
      these antigens in six human neuroblastoma cell lines with and without genomic
      amplification of the N-myc oncogene. All six were stably transduced with an MoMLV
      based gamma-IFN retroviral vector (DAh gamma-IFN). G418-resistant cells were
      assayed for MHC-I, MHC-II, B7-1, and neuroblastoma-associated antigen expression,
      as well as for gamma-IFN levels in cell culture supernatants. Sustained gamma-IFN
      production, 2 to > 1000 units/10(6) cells/d, was attained for five of six
      transduced cell lines and persisted for up to 9 months. This resulted in marked
      upregulation of MHC-I and MHC-II expression in LA-N-1, LA-N-6, and CHLA-127 cells
      and moderate upregulation in SK-N-Fi and SK-N-AS cells. One cell line (LA-N-1)
      had marked induction of MHC-I and MHC-II despite marginal levels of gamma-IFN
      production. Expression of CD28 ligand B7-1 (as determined by BB1 antibody)
      remained unchanged in all gamma-IFN-transduced cell lines tested. Expression of
      several neuroblastoma-associated antigens (NKH1A, 126-4, HSAN 1.2, HNK, 459, and
      390) was upregulated in some of the gamma-IFN-transduced cell lines. These
      results demonstrate that preparation of gamma-IFN expressing neuroblastoma cells
      for immunotherapeutic purposes is feasible and that gamma-IFN transduction
      results in phenotypic changes that may improve immunogenicity of human
      neuroblastoma cells.

PMID- 8528961
TI  - Interleukin-2-secreting mouse fibroblasts transfected with genomic DNA from
      murine neoplasms induce tumor-specific immune responses that prolong the lives of
      tumor-bearing mice.
AB  - Genetic alterations are a common feature of the malignant phenotype. Among other
      properties, altered genes may be responsible for invasion and metastasis, as well
      as for resistance to chemotherapeutic agents. Under appropriate circumstances,
      the products of other altered genes expressed by malignant cells may act as tumor
      associated T-cell epitopes, capable of provoking antitumor immune responses. As a
      novel means of augmenting the immunogenicity of the gene products,
      unfractionated, sheared genomic DNA from various tumor cell lines (B16F1
      melanoma, B16F10 melanoma, MOPC-315 plasmacytoma, C1498 lymphoma, or J558
      myeloma), or from non-neoplastic liver cells of tumor-free mice, was transfected
      into LM cells, a mouse fibroblast cell-line (H-2k) that had been modified
      previously by retroviral gene transfer to secrete interleukin-2 (IL-2). The IL-2
      secreting transfected cell populations were then tested for their immunogenic
      properties toward B16F1 (H-2b) or C1498 (H-2b) cells in syngeneic C57BL/6 mice.
      The antitumor responses were specific for the type of tumor from which the DNA
      was obtained. The survival of C57BL/6 mice injected with a mixture of viable
      B16F1 cells and IL-2-secreting LM cells transfected with DNA from B16F1 cells was
      significantly prolonged. In a similar manner, the survival of C57BL/6 mice
      injected with a mixture of C1498 cells and IL-2-secreting LM cells transfected
      with DNA from C1498 cells was prolonged as well. The immunity was mediated
      predominantly by CD8+ and natural killer/lymphokine-activated killer (NK/LAK)
      cells. These data raise the possibility that a cell line altered previously for
      cytokine secretion may be readily modified to provide immunologic specificity for
      the neoplasms of individual cancer patients.

PMID- 8528962
TI  - Gene therapy for hepatocellular carcinoma: chemosensitivity conferred by
      adenovirus-mediated transfer of the HSV-1 thymidine kinase gene.
AB  - We have investigated whether adenovirally mediated gene transfer of the herpes
      simplex thymidine kinase gene to human hepatocellular carcinoma (HCC) cell lines
      can sensitize these cells to the prodrug ganciclovir and thereby provide a
      therapeutic option for this intractable cancer. Two replication-deficient
      adenoviruses encoding for the herpes simplex virus type-1 (HSV) thymidine kinase
      (TK) gene were generated in which expression of TK is under the control of either
      the human cytomegalovirus immediate early promoter (CMV) or the human alpha
      fetoprotein (AFP) promoter/enhancer. We demonstrate that the combination of
      adenovirally mediated TK gene transfer and ganciclovir treatment effectively
      inhibits proliferation and causes cell death of HCC cells in vitro and that in
      vivo TK gene transfer and ganciclovir treatment inhibits hepatocellular tumor
      growth in a mouse model of this cancer. Furthermore, we show that expression of
      the TK gene can be restricted to those HCCs that express the tumor marker AFP
      through the incorporation of the AFP enhancer/promoter within an adenoviral
      vector.

PMID- 8528963
TI  - Suppression of lung cancer cell growth by ribozyme-mediated modification of p53
      pre-mRNA.
AB  - An anti-p53 ribozyme (catalytic RNA) designed to cleave the p53 pre-messenger RNA
      (mRNA) can efficiently reduce the level of endogenous mutant p53 mRNA. Retrovirus
      mediated transduction of a hammerhead ribozyme (Rz5a) designed to cleave
      unspliced p53 RNA at codon 187 near the boundary of intron 5 and exon 6 reduced
      the level of mutant p53 RNA and protein in the human H226Br lung cancer cell
      line, which contains a homozygous p53 mutation at codon 254. The catalytic
      cleavage of the p53 pre-mRNA but not the p53 mRNA by the ribozyme was shown in
      vitro. The cleavage of the p53 pre-mRNA by this ribozyme was specific because a
      mutation in its catalytic domain (Rz5m) abolished the cleavage activity in vitro.
      Expression of the Rz5a ribozyme significantly suppressed the growth of the H226Br
      cells in culture. However, another ribozyme (Rz7a) targeted at codon 264 of the
      p53 gene near the boundary of intron 7 and exon 8 showed in vitro cleavage of the
      pre-mRNA but did not suppress cell growth. The site of modification in the p53
      pre-mRNA may determine the degree of ribozyme-mediated growth suppression in this
      cell line. Our findings that p53 pre-mRNA can be modified by a specific ribozyme
      in vivo suggest a possible role for these agents in gene therapy strategies for
      cancer.

PMID- 8528964
TI  - Antisense oligodeoxyribonucleotide down-regulation of bcl-2 gene expression
      inhibits growth of the low-grade non-Hodgkin's lymphoma cell line WSU-FSCCL.
AB  - The BCL-2 gene product is involved in preventing apoptosis. The t(14,18)
      chromosomal translocation, which results in a fusion messenger RNA containing the
      entire coding region of BCL-2 and a portion of the immunoglobulin heavy chain
      gene, is commonly found in follicular lymphoma and appears to play a role in
      lymphomagenesis by inhibiting cell death. We tested the hypothesis that
      downregulation of BCL-2 would decrease accumulation of follicular lymphoma cells
      by treating the t(14,18)-carrying follicular lymphoma cell line WSU-FSCCL in
      vitro with antisense oligodeoxyribonucleotides (ODNs) directed against BCL-2. We
      found dose-dependent, sequence-specific inhibition of cell accumulation by an
      antisense unmodified ODN directed at codons 2 to 7, which downregulated BCL-2
      protein levels. This effect was near maximal at an ODN concentration of 40
      micrograms/mL (6.9 mumol/L), with minimal toxicity by control sense, reverse, and
      mutated antisense ODN at the same concentration. The pre-B leukemia cell line REH
      showed no sequence-specific growth inhibition by the antisense ODN at these
      concentrations, and BCL-2 protein levels were not altered. These data suggest
      that WSU-FSCCL may be useful in a murine model to optimize antisense ODN for
      potential therapeutic utility.

PMID- 8528965
TI  - Application of ribozymes to cancer gene therapy.

PMID- 8528966
TI  - Adjuvant therapy for resectable gastric adenocarcinoma: preoperative and
      postoperative chemotherapy trials.
AB  - Survival rates for patients undergoing resection of gastric adenocarcinoma remain
      poor. Even following successful removal of all gross disease, high rates of local
      regional and systemic recurrence are observed. During the past twenty-five years,
      multiple trials have been undertaken to evaluate the possible benefit of either
      preoperative or postoperative adjuvant chemotherapy in this disease. This report
      reviews the rationale, design, and outcome of these trials, and further updates
      the status of preoperative chemotherapy protocols currently employed at the M.D.
      Anderson Cancer Center.

PMID- 8528967
TI  - The role of chemotherapy for metastatic gastric cancer.
AB  - Gastric cancer is one of the most chemosensitve tumors of the gastrointestinal
      tract. Chemotherapy treatment in patients with metastatic disease has been shown
      to improve quality of life and prolong survival. There are a number of second
      generation active regimens that give high response rates and are currently being
      assessed in phase III studies. Ultimately these regimens will find their role in
      the preoperative and adjuvant setting. At present, in patients with metastatic
      disease, there is a need to compare these regimens to single-agent schedules with
      less toxicity. Continued optimism is necessary in gastric cancer with new types
      of drugs, high-dose treatment and revisiting old drugs--all potential ways of
      increasing the cure rate in this disease.

PMID- 8528968
TI  - The role of irradiation as a component of combined modality treatment for gastric
      cancer.
AB  - Adjuvant therapy following complete surgical resection of gastric cancers is
      indicted on the basis of failure patterns and survival results with surgery alone
      (high incidence of local-regional relapse and distant metastases). To date,
      however, single modality adjuvant therapy has not had a meaningful impact on
      outcome (disease control or survival). Most Western chemotherapy trials are
      negative for both single and multiple drugs. Irradiation alone reduces local
      regional relapse but doesn't alter survival. Data from single institution phase
      II and small phase III trials suggest that combined modality adjuvant therapy
      (irradiation plus chemotherapy) may have a positive outcome on both disease
      control and survival. A U.S. intergroup trial is therefore underway to further
      evaluate disease control and survival benefit trends for combined modality
      postoperative irradiation plus chemotherapy that were found in a small Mayo
      Clinic randomized study. For patients with locally advanced disease (locally
      unresectable or resected but residual disease), combined external irradiation
      plus chemotherapy or intraoperative irradiation (IORT) produces long-term
      survival in 10% to 20% of patients in most randomized and nonrandomized trials.
      Studies using preoperative (neoadjuvant) chemotherapy for locally unresectable
      disease reveal a possible increase in resection rates but a high incidence of
      local-regional relapse. It would be of interest to merge together those
      treatments that have produced apparent improvements in response rates, disease
      control, or survival for locally advanced disease (add external radiation plus
      concomitant chemotherapy, IORT, or combinations thereof to preoperative
      chemotherapy regimes.

PMID- 8528969
TI  - Four days' continuous infusion of cisplatin-5-fluorouracil and short daily
      infusion of high-dose leucovorin as induction chemotherapy for locally advanced
      head and neck cancer.
AB  - Cisplatin-fluorouracil (PF) is the most frequently used combination as induction
      chemotherapy (CT) for the treatment of locally advanced squamous cell head and
      neck cancer. This study was designed to evaluate the role of leucovorin (L) in
      the modulation of the therapeutic activity of PF continuously infused for 4 days.
      Between June 1990 and June 1992, stage III and IV previously untreated patients
      received PFL induction chemotherapy followed by surgery, radiotherapy, or both.
      The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused
      for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF.
      PFL was administered every 3 weeks for 4 cycles. The overall response rate at the
      completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was
      performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus
      radiotherapy, and 37 (54%) radiotherapy. Complete response status after both
      induction and locoregional therapy was 71%. Biopsies of the primary tumor or
      definitive resection specimens immediately after PFL therapy were available in 25
      patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up
      of 44 months, the overall survival rate is 51% and the median survival has not
      been reached. PFL is highly active as induction chemotherapy. A randomized
      comparison between PF and PFL is necessary to define the place of leucovorin
      modulation in the treatment of head and neck cancer.

PMID- 8528970
TI  - Low-dose, continuous infusion 5-fluorouracil and oral etoposide for the treatment
      of advanced sarcomas.
AB  - 5-fluorouracil (5-FUra) and etoposide demonstrate relationships between schedule
      of administration and activity in a number of clinical situations. With limited
      information regarding 5-FUra and oral etoposide in sarcoma, and informal
      observations suggesting activity of infusional 5-FUra in sarcomas, a phase II
      study was performed. This phase II study attempted to evaluate the efficacy of
      the combination of low-dose continuous infusion 5-FUra (LDCI-5FUra) and oral
      etoposide administered to patients with advanced sarcomas. Treatment consisted of
      5-FUra at 300 mg/m2/day and etoposide at 50 mg/m2/day for 21 days. Cycles were
      repeated at 28-day intervals or upon recovery from toxicity. Twenty patients
      received 50 cycles of therapy. No objective responses were seen in 19 evaluable
      patients (response rate 0%, 95% confidence interval 0-18%). Toxicity was mild and
      consisted primarily of stomatitis, diarrhea, and leukopenia. Median survival for
      all patients was 9 months (1.8-30+ months range). The combination of LDCI-5FUra
      and oral etoposide, at the doses and schedule studied, was inactive in this
      population with advanced sarcoma.

PMID- 8528971
TI  - Biology of gastric cancer: gastritis-metaplasia-dysplasia sequence, role of H
      Pylori, and molecular correlates of tumor progression.

PMID- 8528972
TI  - Surgical therapy for gastric cancer.
AB  - The aim of any surgical approach to gastric carcinoma should be a complete
      resection with no residual tumor left behind, that is, a R0-resection according
      to the UICC. Complete tumor resection in this respect refers to the primary tumor
      as well as the lymphatic drainage and requires an adequate safety margin. The
      indications for surgical therapy of gastric cancer and the choice of procedure
      should consequently be guided by the tumor stage. This requires accurate
      preoperative staging, which can today be achieved with endoscopic ultrasonography
      and surgical laparoscopy. Gastric carcinoma stage IA (mucosa carcinoma) can be
      cured by local excision. In patients with tumor stages IB (submucosa carcinoma),
      II, and IIIA, lymph node metastases are common. Based on the available data, this
      group of patients benefits from radical resection and D2 lymph node dissection.
      In patients with advanced gastric carcinoma, that is, tumor stages IIIB and IV, a
      complete tumor removal usually can not be achieved by surgical resection.
      Neoadjuvant therapeutic modalities should consequently be assessed in these
      patients. Based on tumor location and growth pattern, a total gastrectomy is the
      procedure of choice in patients with middle and proximal third gastric cancer. A
      subtotal gastrectomy may be performed in patients with tumors of the distal third
      and "Lauren's intestinal type" growth pattern. Depending on the individual tumor
      situation, the gastrectomy can be extended toward varying portions of the distal
      esophagus or a pancreas, preserving splenectomy and resection of the
      retroperitoneal lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528973
TI  - Chronomodulated 5-day infusion of floxuridine and L-folinic acid in patients with
      advanced malignancies: a feasibility and tolerability study.
AB  - The best schedule for administering floxuridine (FUDR) has not yet been
      established. Duration of infusion, need (and dosage) of leucovorin (folinic acid,
      FA), and circadian timing need to be further specified. Nevertheless, FUDR
      delivery according to circadian rhythms has allowed increase of dose intensity
      without enhancing the side effects. A 5-day infusional schedule combining FUDR
      and L-FA was devised as an attempt to increase dose intensity and to provide
      therapy every 3 weeks to patients with advanced cancer. An ambulatory
      programmable-in-time pump was used for this purpose. Fourteen patients entered
      this trial. Two dose levels (mg/kg x 5 days) were evaluated: 0.5 mg/kg/day in six
      patients and 0.525 mg/kg/day in eight patients. Both patient groups received a
      concurrent infusion of L-FA 10 mg/m2/day i.v. The delivery patterns of both FUDR
      and L-FA varied sinusoidally during the 24 hours with a maximum at 18.00 hours.
      Courses were repeated every 3 weeks. Of 35 courses, treatment produced mucosites
      greater than grade 2 in only two of them. No severe diarrhea, the dose-limiting
      toxicity of FUDR when infused over 14 days, was encountered at the dose levels
      tested. This 5-day chronotherapy schedule allowed delivery of a larger amount of
      FUDR than the flat delivery described in a previous report. A daily dose of 0.525
      mg/kg FUDR, combined with 10 mg/mg2 L-FA, with intraindividual dose escalation
      according to tolerance, is recommended for future investigations of the activity
      of this chronotherapy schedule.

PMID- 8528974
TI  - Personality, inner experience and compliance in advanced cancer patients treated
      with external pumps.
AB  - The presence of portable pumps for protracted infusional chemotherapy in
      metastatic solid tumors at an advanced stage determines the need to evaluate
      psychologically the inner experience of the patients in relation to this
      therapeutic modality. The objective of the study were to analyze personality
      variables (coping and awareness), inner experience variables (acceptance and
      expectations) and the compliance of the patients during repeated courses of
      therapy. In addition we evaluated the influence of sex, age, level of education
      and response to treatment in relation to these variables. From February 1992 to
      March 1994 we evaluated 50 metastatic patients with a psycho-dynamic interview at
      the 1st, 3rd, 6th and the 9th course of therapy. The data obtained showed a
      positive trend for all the variables examined and in all the subgroups (age, sex,
      level of education, response) up to the 6th course. After the 6th course,
      personality variables remained stable, yet a drop in variables related to inner
      experience and compliance was observed in the whole group. While the personality
      variables remain constant in all patients, a decrease of acceptance and
      expectation was observed in patients non responding to therapy for their tumor, a
      trend which becomes significative at the 9th course regards expectation. The use
      of a psycho-dynamic interview allowed us to evaluate the effect of treatment on
      psychological variables and compliance to therapy. The length of treatment and
      the response to treatment seem to influence the more profound inner experiences
      of the patients.

PMID- 8528975
TI  - Circadian rhythm-modulated (CRM) chemotherapy of metastatic breast cancer with
      mitoxantrone, 5-fluorouracil, and folinic acid: preliminary results of a phase I
      trial.
AB  - A phase I feasibility trial with a 5-day schedule of circadian rhythm-modulated
      mitoxantrone (MIT), 5-fluorouracil (5-FU, 600 mg/m2/day), and folinic acid (FA,
      300 mg/m2/day) was performed in patients with metastatic breast cancer. The MIT
      dose was escalated from 2 to 2.5 and 2.75 mg/m2/day in consecutive groups of six
      patients. All three drugs were infused intravenously with a multichannel
      ambulatory pump. Maximal delivery rate was programmed at 4.00 hours for 5-FU and
      FA and at 16.00 hours for MIT. Eighteen women with advanced metastatic breast
      cancer were included in the trial between April 1991 and July 1993. Seventeen of
      18 patients had received previous chemotherapy, which contained anthracyling for
      16 of them. Tolerability of the first treatment course was assessed 10 and 21
      days after course onset. Neutropenia was dose dependent and the most frequent
      toxicity (grade 3: 4 patients; grade 4: 7 patients), yet only a single
      hospitalization was required for fever and neutropenia. A single patient
      exhibited grade 3 mucositis. No grade 3 or 4 diarrhea, nausea, or vomiting was
      encountered. This chronomodulated infusion of MIT, 5-FU, and FA showed acceptable
      toxicity in heavily pretreated patients. For the phase II evaluation of the
      antitumor activity of this circadian schedule, a dose of 2.75 mg/m2/day of MIT is
      recommended using a monthly regimen. Further dose escalation may be performed in
      patients without bone metastasis and good performance status.

PMID- 8528976
TI  - Ambulatory chronotherapy with 5-fluorouracil, folinic acid, and carboplatin for
      advanced non-small cell lung cancer. A phase II feasibility trial.
AB  - Thirty-two patients with advanced non-small cell lung carcinoma (NSCLC) received
      a chronomodulated 5-day venous infusion of 5-fluorouracil (5 FU) (700 mg/m2/day),
      folinic acid (F) (300 mg/m2/day), and carboplatin (C) (40, 50, or 55 mg/m2/day),
      as first chemotherapy. Courses were repeated every 21 days (after a 16-day
      interval). In total, 158 courses (median: 4, range: 1 through 16; 81 and 58
      courses at, respectively, a 40 and 50 to 55 mg/m2 daily dosage of C) were
      delivered using a multichannel programmable in-time pump (Intelliject, Aguettant)
      connected to a double lumen implanted venous side-port. The administration was
      allowed in fully ambulatory convenience. Overall tolerance was excellent. Grade 3
      of 4 hematologic toxicity was encountered in 4.6% of courses for thrombopenia and
      in 7.0% of courses for neutropenia. Nausea or vomiting (grade 3 or 4) occurred in
      7.8% of courses. Mucositis, diarrhea, alopecia, or skin grade 3 or 4 toxicity
      were observed in less than 3% of courses. Treatment delay was needed in only 7.8%
      of courses and dose reductions were needed in 4.6% of courses for 5 FU and in
      6.5% of courses for C. This good tolerance allowed a sustained quality of life
      and prompted further trials aiming to define the place of this protocol in the
      multidisciplinary treatment approach of NSCLC.

PMID- 8528977
TI  - A phase I-II trial of five-day continuous intravenous infusion of 5-fluorouracil
      delivered at circadian rhythm modulated rate in patients with metastatic
      colorectal cancer.
AB  - The toxicity of 5-fluorouracil (5-FU) was decreased by two to eight-fold if this
      drug was injected in mice near the middle of the day (rest span) rather than in
      the middle of the night (activity span). If the rhythm in 5-FU toxicity is linked
      to the sleep-wakefulness endogenous circadian cycle across species, the least
      toxic time in man would correspond to 4.00 hours at night. The availability of a
      single-reservoir programmable-in-time external ambulatory pump (Chronopump,
      Autosyringe, Hooksett, USA) allowed us to perform a first test of this
      hypothesis. Five-FU was infused for 5 consecutive days, via an implanted venous
      access port, with peak drug delivery at 4.00 hours and no infusion from 18.00 to
      22.00 hours. Each course was repeated after a free interval of 16 days.
      Intrapatient dose escalation was planned from 4 to 9 g/m2/course (800 to 1800
      mg/m2/day x 5 days) if toxicity was less than grade 2 according to the World
      Health Organization (W.H.O.). Thirty-five patients with metastatic colorectal
      cancer were treated; 15 (41%) had received previous therapy, 22 (63%) had W.H.O.
      performance status of 2 or greater, and 19 (54%) had two or more sites involved.
      Grade 2 or greater toxicity was encountered in less than 5% of the courses,
      indicating an adequate control of toxicity via dose adjustment. Oral mucositis,
      diarrhea, and/or hand-foot syndrome limited dose escalation, and their incidence
      was dose dependent. Median maximal tolerated dose was 7.5 mg/m2/course in 30
      patients assessed for this endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8528978
TI  - Current concepts for chronochemotherapy of cancer.
AB  - In this article, a survey on the concepts and scientific basis for applying
      chemotherapy against malignant tumors on a circadian schedule is given. The idea
      is to give the cytostatic drugs at times of the day when optimal effect on the
      tumor is achieved, but at the same time causing minimal toxic side effects.
      Following a brief description of the complexity of cancer tissue, some aspects of
      the present status of cancer chemotherapy in general are reviewed. Applications
      of chronobiology in cancer treatment are then surveyed together with
      possibilities to increase cytostatic doses and reduce side effects. When optimal
      tumor cell kill is achieved, the next step is to address the circadian aspects of
      normal organs, including the proliferative behavior of tissues with rapid cell
      renewal. Finally, the question of how regulatory mechanisms responsible for
      normal circadian rhythms can be interfered with is addressed. Cancer
      chronochemotherapy today combined with modern infusional technology is a
      promising field for improving cancer treatment in general and reducing side
      effects and is expected to make important progress in the near future.

PMID- 8528979
TI  - Endothelial cell activation in shock.
AB  - Some pathological conditions including shock, induce focal activation,
      degeneration, necrosis and desquamation of endothelial cells. These changes cause
      disturbances of endothelial functions which include expression of adhesive
      molecules resulting in rolling of the leukocytes along endothelial surface, loss
      of endothelial adhesiveness to subendothelial matrix resulting in cell
      desquamation, dysfunction of endothelial anticoagulation/coagulation balance and
      disturbances of endothelial vasomotor abilities. Above mentioned imbalance of
      endothelial functions are discussed in aspects of shock.

PMID- 8528980
TI  - Activation of the peritoneal mast cells and eosinophils in untreated hemorrhagic
      shock in rats.
AB  - The mast cells and eosinophils washed out from rat peritoneal cavity after 75
      minutes of untreated hemorrhagic shock were studied in light and electron
      microscope. A significantly increased total peritoneal cell (PC) number, an
      increased mast cell (MC) number, decreased eosinophil number, and features of
      activation of both MC and E were found: heterogeneity and combining of granules,
      evacuation of their content, build up and enlargement of endoplasmic reticulum,
      development of microtubular cytoplasmic system, multiplication of cell membrane
      microvilli, and contacts between MC and E. Ultrastructural examination revealed
      vesicle formation in Golgie apparatus. These vesicles created characteristic
      blebs on the cell surface and evacuated their contents outside. Morphological
      findings suggest that peritoneal mast cells and eosinophils are involved in
      mechanism of the intestinal injury in shock.

PMID- 8528981
TI  - Increase in the peritoneal antioxidative potential in experimental hemorrhagic
      shock.
AB  - Production of the oxygen-derived free radicals in peritoneal lavage after one
      hour hemorrhagic shock were investigated on a rat model. A statistically
      significant increased activity of superoxide dismutase (SOD), and an
      insignificant enhancement of concentration of -SH groups, comparing to the
      control animals was shown. There was no difference in the level of
      malondialdehyde (MDA) in the peritoneal fluid from the bled animals and the
      control group. The results indicate an increased antioxidative potential of the
      peritoneal content in the early phase of hemorrhagic shock.

PMID- 8528983
TI  - Pathogenesis and treatment of multiorgan failure dysfunction syndrome in shock.
AB  - Pathogenesis and treatment of multiorgan dysfunction syndrome (MODS) have been
      presented, basing on literature and own experience. The term multiple organ
      dysfunction syndrome--MODS is now regarded to be the most accurate. The
      classification and the pathogenesis of primary and secondary MODS are discussed.
      In the primary MODS causes are to be looked for in the extensive injuries of
      tissues, hypoxia and the ischemia-reperfusion syndrome. In the secondary MODS,
      because of the effects of other deteriorative factors, the systemic infection
      response syndrome (SIRS) appears. The course of this reaction has been discussed,
      pointing the attention to the effects of proinflammatory cytokins (mainly TNF
      alpha), then to the role of neutrophils and the intestinal translocation. Various
      approaches to the prevention and treatment of MODS are presented. In the primary
      MODS very important is an appropriate tissue perfusion restoration and
      elimination of necrotic tissue. In the secondary MODS there are new ways of
      treatment. Used are: monoclonal antibodies, antioxidants, inhibitors of cytokins
      and proteases, hemofiltration, selective bowel decontamination. Enteral
      nutrition, if possible--provides not only the supply of food substrates but it
      may also inhibit cytokin release, decrease translocation and improves
      hemodynamics. The prognosis in MODS is still very serious, however, its
      improvement is to be regarded after the application of new therapeutic methods.

PMID- 8528982
TI  - Luminol-chemiluminescence in free peritoneal cells in hemorrhagic shock in rats
      treated with PAF-receptor-antagonist BN 52021.
AB  - The activity of rat peritoneal cells were assessed by the phorbol mirystinian
      acetate (PMA)-induced luminol chemiluminescence (LCL). Results in control groups
      (0 - no manipulation, and I - carotid artery cannulation) were compared with
      those in the untreated hemorrhagic shock (group II), in the shock treated with
      the standard polyelectrolyte solution (PES) (group III), and in shock treated
      with PAF receptor-antagonist BN 52021 + PES (group IV). The maximal and the most
      rapid LCL was observed in the group treated with BN 52021 (group IV), while
      chemiluminescent response in the the untreated shock (group II) and in shock
      treated with PES was minimally expressed and late. The findings indicate for a
      rapid activation of peritoneal cells during ca 1 hour of hemorrhagic shock. This
      leads to exhausting their ability to the superoxide anion generation 15 minutes
      later. Peritoneal cells obtained from the group treated with the BN 52021
      revealed a preserved ability to the respiratory burst. It can be concluded that
      BN 52021 effectively inhibits activation of the PC during hemorrhagic shock.

PMID- 8528984
TI  - Cathepsin D activity in the intestinal wall in experimental untreated hemorrhagic
      shock.
AB  - The total cathepsin D activities in the intestinal wall and in venous mesenteric
      and arterial systemic blood were investigated on the rats in untreated
      hemorrhagic shock lasting 60 minutes. We observed a decrease in cathepsin D
      activity in homogenates of respective segments of small and large bowels and an
      increase in the enzyme activity in blood serum of both origin. The shock resulted
      in lowering protein concentration in the intestinal wall and its increase in the
      mesenteric blood. We found a negative correlation between cathepsin D activity in
      the intestinal wall and its morphological destruction. Molecules of the enzyme,
      after liberation from lysosomes due to hemorrhagic shock, are translocated to the
      circulation and probably to the gut lumen. Liberation of the intestinal cathepsin
      D may contribute to the local damage and multiorgan failure in hemorrhagic shock.

PMID- 8528985
TI  - Activity of exoglycosidases of the rat abdominal organs in untreated hemorrhagic
      shock.
AB  - Exoglycosidases catabolize glycoconjugates (proteoglycans, glycolipids and
      glycoproteins) at a rate depending on tissue and pathological changes. We
      determined exoglycosidase activity in successive sections of alimentary tract,
      spleen, liver and kidney of rats subjected to hemorrhagic shock. We found
      significant difference in exoglycosidase activity between alimentary tract
      segments in control animals and no significant changes in homologous tissues of
      the shocked rats comparing with control.

PMID- 8528986
TI  - Disturbances of hemostasis during declamping shock.
AB  - The aorta, above or below renal arteries was clamped for 60 minutes, in a canine
      model. The blood was taken for testing from above the aorta bifurcation before
      clamping, after 30 minutes of its duration, directly after declamping and every
      30 minute during next 4 hours. Irrespective of clamping level, the platelet
      count, clot retraction and prothrombin consumption do not undergo significant
      changes. However, the activity of platelet factor 4 is increased. Prothrombin
      time, recalcination time, kaolin-kephalin time and the activities of factors V,
      VII, XI and XII do not differ as well. Thrombin time is prolonged and
      antithrombin III activity is reduced. Euglobulin fibrinolysis time undergoes
      prolongation and antiplasmin content is increased. The observed changes show a
      variable tendency, regardless of clamping level and increase with the passage of
      experiment time. An increase in the coagulation activity and a decrease in the
      fibrinolytic activity of the blood plasma may be a resultant of the changes.
      Finally it may promote thrombus formation and indicates the preventive use of
      heparin.

PMID- 8528987
TI  - Hemostatic activity of organs in declamping shock.
AB  - The aim of the study was to determine the haemostatic components activity of
      organs in declamping shock. The abdominal aorta was cross-clamped below or above
      renal arteries. No significant changes in tromboplastic and antithrombin
      activities were found in the kidney, liver, lung, heart and skeletal muscle.
      Renal cortex and medulla as well as the lungs show higher plasminogen activator
      activity and considerably higher antiplasmin activity. Diminished fibrinolysis in
      the kidney and the lung may promote thrombotic complications.

PMID- 8528988
TI  - Activity of membrane, cytosol and lysosome enzymes in organs and blood serum
      during declamping shock.
AB  - The aim of the study was to evaluate the enzyme activity of cellular membranes
      (GGT), cytosol (ALT, AST) and lysosome (AP, AcP) in the cytosol, whole homogenate
      and blood serum during declamping shock, following release of abdominal aorta
      cross-clamping. The aorta was clamped for 60 minutes. An increase in GGT, AP and
      AcP activities in the cytosol and whole homogenate of the renal cortex, renal
      medulla, liver, lung, heart and the skeletal muscle occurs after declamping. Rise
      in the enzymatic activity, especially of acid phosphatase is higher when the
      aorta above renal arteries was clamped. However, its activity in the blood serum
      remains unchanged. Alterations in the distribution and the activity of the
      studied enzymes may indicate that aortic clamping damages the endoplasmic
      reticulum and lysosomal membranes. Yet, cellular membranes preserve their
      structural and functional integrity.

PMID- 8528989
TI  - Cathepsin D activity and protein degradation products in organs and blood during
      experimental declamping shock.
AB  - Aortic cross-clamping in dogs for 60 min causes an increase in cathepsin D
      activity in the kidney, liver, lung, heart, skeletal muscle and the blood serum.
      It causes no changes in the content of protein and its degradation products of
      the examined organs, apart from the lungs, where the above parameters are higher.
      The intensity of the observed changes in the kidney and other organs does not
      depend on the level of aortic cross-clamping (above or below renal arteries).

PMID- 8528990
TI  - Evaluation of the results of endotoxic shock (ES) treatment with dopamine (DA)
      and hydrocortisone (H).
AB  - The aim of this report is to present complex evaluation of the applied treatment
      with dopamine (DA) and hydrocortisone (H) in experimental endotoxic shock (ES).
      An evaluation is based on long-term experiences of the author's Clinic. The
      studies were performed in dogs. ES was evoked by intravenous E. coli endotoxin
      administration in a dose of 2 mg/kg. An appearance and progress of ES was
      evaluated by determination of many hemodynamic and biochemical parameters. In the
      treatment DA and H were used. Besides of mentioned above parameters also
      morphological, histochemical and ultrastructural investigations of the lung and
      liver were done. DA and H applied together were the most effective treatment in
      the course of ES. It could be a theoretical ground for combined ES treatment in
      people.

PMID- 8528991
TI  - Energy expenditure (EE) and substrate utilization (SU) in the perioperative
      period in orthotopic liver transplantation (OLTX).
AB  - 12 patients were investigated with IC (Datex, Deltatrac) preoperatively and
      during the surgical procedure of OLTX, VO2, VCO2 were continuously measured and
      RQ, EE and SU were calculated considering the different periods of the procedure:
      preoperative resting EE: (PREE), anaesthesiological procedures (ANEE), liver
      preparation EE (LPEEE), liver removal EE (LREE), anhepatic phase EE (APEE),
      reperfusion, EE (RPEE) and end of operation EE (EOEE). EE were expressed as %
      respect value calculated with H.B. (Harris-Benedict) formula. Data were analyzed
      with Student T-test and p < 0.01** or < 0.05* PREE is typical in end stage liver
      disease with low RQ values and increased EE. Energy production depends on lipid
      utilization since liver gluconeogenesis and glycogen stores are impaired.
      Anesthesia reduces energy needs and production up to 50% of the preoperative
      values, reducing VO2 more than VCO2 and therefore an augmented RQ value over 1.0.
      SU analysis indicates an increased glucose and aminoacid utilization coupled with
      high nitrogen catabolism that continues in the postoperative period (from 0.08
      0.01 gN/kg b.w. to 0.20 0.06 gN/kg b.w.). When the new liver is reperfused, VO2
      increases more than VCO2 indicating the risk of reperfusion injury.

PMID- 8528992
TI  - The activity of cathepsin A and cathepsin D in the serum of persons acutely
      intoxicated with ethanol and chronic alcoholics.
AB  - The activity of cathepsin A, cathepsin D and other enzyme-markers of liver damage
      (ASPAT, ALAT, GGTP, LDH, AP) were measured in the serum of persons acutely
      intoxicated with ethanol and chronic alcoholics. Persons acutely intoxicated with
      ethanol had the unchanged activity of cathepsin A and cathepsin D while it
      increased in the chronic alcoholic serum.

PMID- 8528993
TI  - Pathophysiology of fluid translocation in hypovolemic state.
AB  - The broad meaning of "trauma" includes: 1)tissue injury, 2)inflammatory reaction,
      and 3)hypovolemic state. There are two arms of body response to "trauma": 1)neuro
      hormonal and 2)konins-cytokines related. In both, compensation of hypovolemia is
      basic, but transmission of inflammatory mediators is dependent on appearanced
      hypervolemic tendency and related to augmented lymph flow. The course of after
      injury fluids translocations consists of three phases: 1. "hemorrhagic", 2.
      sequestration, and 3. mobilization. The sequence of these phases is constant but
      duration is variable and depends on severity of trauma. Increased internal
      translocations of water, electrolytes and protein are required, leading to
      restoration of effective arterial blood volume and disappearance of baroreceptors
      irritation. The phase of compulsory sequestration of fluids involves all body
      fluid compartments. Distribution of fluid between intra- and extracellular
      compartments depends on the nature of "traumatic" stimulus: a) the more the
      tissue injury is related to hypovolemic-neurohormonal arm the more fluid is
      retained in the cells, b) the more the tissue injury is related to kinins
      cytokines related arm the more is the expansion of extracellular compartment with
      increase in plasma volume and lymph flow. Hypoalbuminemia correlates inversely
      with the interstitial fluid volume. Sequestration phase is followed by fluid
      mobilization. Previously negative balance of water and natrium comes to null. In
      case of complications a new sequestration phase should be expected.

PMID- 8528994
TI  - Mast cells in the gastrointestinal tract.
AB  - The morphology and functions of gastrointestinal mast cells (MCs) under
      physiological and pathological conditions were described. Special attention was
      paid to the MCs origin, differentiation and morphological and biochemical aspects
      of their degranulation. Mast cells are important component of normal architecture
      of the gastrointestinal tract. Many substances released from MCs during
      degranulation are biologically active and mediate numerous processes: blood flow
      regulation, epithelial and endothelial permeability, mucosal secretion,
      gastrointestinal tract motility, immunological events related to the antigens of
      various origin, angiogenesis, cancer development. Thus MC is often considered as
      an important agent in pathogenesis of many gastrointestinal diseases. The
      gastrointestinal diseases which was described in this paper are following:
      bacterial and parasitic infections, peptic ulcer, ulcerative colitis, Lesniowski
      Crohn's disease, inflammatory polyps, intestinal graft-versus-host reaction,
      neoplastic tumors, mastocytosis, intestinal ischemia.

PMID- 8528995
TI  - Peritonitis biliaris: some aspects of its origin.
AB  - As a cause of septic shock, peritonitis biliaris is a very serious condition. We
      stress the risks of its development and necessity of postoperative drainage in
      laparoscopic cholecystectomy. The risks include a cholascos which may develop
      after some radical procedures of a "non-operative" nature on the liver parenchyma
      and bile passages (transperietal or endoscopic procedures).

PMID- 8528996
TI  - Ginkgolide BN 52021 protects against hemorrhagic shock-induced renal injury in
      rats.
AB  - Degree of renal damage in experimental untreated and treated hemorrhagic shock
      was estimated in light microscopy. Histological preparations were scored with a
      semiquantitative scale concerning the changes which are typical for the acute
      renal failure. It was found that an early treatment with the PAF-receptor
      antagonist (ginkgolide BN 52021) considerably reduced morphological changes
      observed in rat kidney in hemorrhagic shock, comparing with untreated shock and
      in shock treated with a polyelectrolyte solution.

PMID- 8528997
TI  - Oxygen-derived free radicals in kidney in experimental hemorrhagic shock treated
      by PAF-receptor antagonist BN 52021.
AB  - Renal damage in rat hemorrhagic shock model was assessed by estimation of the
      reactive oxygen metabolites generation (malondialdehyde measured as
      thiobarbituric acid reactive substances) and antioxidative potential (activity of
      Cu-, Zn- superoxide dismutase, activity of glutathione reductase and level of
      sulfhydryl compounds). It was found that treatment with BN 52021 (a platelet
      activating factor antagonist), and polyelektrolyte solution had had a beneficial
      effect in comparison with both the untreated shock and shock treated by
      reperfusion only.

PMID- 8528998
TI  - Megakaryocytes in the acute stage of experimental hemorrhagic shock. Part I.
      Megakaryocytes circulating in the blood.
AB  - Megakaryocytes were evaluated in the blood of the caval vein of rats in the acute
      stage of hemorrhagic shock. The number and morphological types of MK were
      analysed. Millipore filters were used for the evaluation. MK were found to be a
      physiological element of the blood. An increase in the MK number leaving the bone
      marrow in rats with the acute stage of hemorrhagic shock was observed. A rise in
      the total MK number was accompanied by an increase in the percentage of mature
      and "naked nucleus" MK.

PMID- 8528999
TI  - Megakaryocytes in the acute stage of experimental hemorrhagic shock. Part II.
      Megakaryocytic regulation of cell release from the bone marrow.
AB  - The contribution of MK to the release of other marrow cells to the blood was
      evaluated in rats subjected to experimental hemorrhagic shock. The analysis was
      based on the frequency of emperipolesis phenomenon in megakaryocytes, which was
      evaluated in a light microscope on marrow smears and in ultrastructural
      examinations. A considerable increase was found in the number of marrow cells in
      the MK cytoplasm in the animals examined, which indicates a significant part of
      MK in the release of these cells to the blood and in the marrow-blood barrier
      formation by MK.

PMID- 8529000
TI  - Megakaryocytes in the acute stage of experimental hemorrhagic shock. Part III.
      Histomorphometrical evaluation of megakaryocytes.
AB  - The authors presented the morphometrical evaluation of the bone marrow MK in rats
      in the acute stage of experimental hemorrhagic shock. The experiments used a
      semiautomatic computer programme. The total number of MK per 1 mm2 of the bone
      marrow was analysed with regard to various morphological forms of MK, their
      surface area, shape disorders, nuclear-cytoplasmic ratio and cluster forms. A
      considerable shift was observed in the MK parameters examined, suggesting a
      significant effect of hemorrhagic shock upon megakaryocytopoiesis.

PMID- 8529001
TI  - Nutritional and physiological characteristics in germ-free chickens.

PMID- 8529002
TI  - Thermoregulatory responses to thermal stimulation of the preoptic anterior
      hypothalamus in the red fox (Vulpes vulpes).
AB  - The preoptic anterior hypothalamus (POAH) thermoregulatory controller can be
      characterized by two types of control, an adjustable setpoint temperature and
      changing POAH thermal sensitivity. Setpoint temperatures for shivering (Tshiver)
      and panting (Tpant) both increased with decreasing ambient temperature (Ta), and
      decreased with increasing Ta. The POAH controller is twice as sensitive to
      heating as to cooling. Metabolic rate (MR) increased during both heating and
      cooling of the POAH. Resting temperature of the POAH was lower than internal body
      temperature (Tb) at all temperatures. This indicates the presence of some form of
      brain cooling mechanism. Decreased Tb during POAH heating was a result of
      increased heat dissipation, while higher Tb during POAH cooling was a result of
      increased heat production and reduced heat dissipation. The surface temperature
      responses indicated that foxes can actively control heat flow from body surface.
      Such control can be achieved by increased peripheral blood flow and vasodilation
      during POAH heating, and reduced peripheral blood flow and vasoconstriction
      during POAH cooling. The observed surface temperature changes indicated that the
      thermoregulatory vasomotor responses can occur within 1 min following POAH
      heating or cooling. Such a degree of regulation can be achieved only by central
      neural control. Only surface regions covered with relatively short fur are used
      for heat dissipation. These thermoregulatory effective surface areas account for
      approximately 33% of the total body surface area, and include the area of the
      face, dorsal head, nose, pinna, lower legs, and paws.

PMID- 8529003
TI  - Acute osmotic tolerance of cultured cells of the oyster pathogen Perkinsus
      marinus (Apicomplexa:Perkinsida).
AB  - Cultured Perkinsus marinus cells were exposed for 24 hr to salinities of 0, 3, 6,
      9, 12 and 22 ppt at temperatures of 1, 5, 10, 15 and 28 degrees C in artificial
      seawater (ASW) and to the same salinities at 28 degrees C in ASW with the osmotic
      concentration adjusted with sucrose to the equivalent of 22 ppt. At 28 degrees C
      mortality increased as salinity decreased below 22 ppt. Mortality was greater
      than 99% at 0 ppt and greater than 90% at 3 ppt. Mortality was 70% at 6 ppt, 43%
      at 9 ppt and 20% at 12 ppt. Mortality was low (< 5%) and equal to that at 22 ppt
      in all treatments where osmotic concentration was maintained with sucrose.
      Mortality occurred rapidly, within 5 min of exposure to experimental conditions.
      In the region where mortality was most sensitive to salinity changes (6-12 ppt),
      lower temperature caused an increase in mortality, but the temperature effect was
      significant only at 9 ppt.

PMID- 8529004
TI  - Electrical responses and K+ activity changes to light in the ocellus of the
      planarian Dugesia japonica.
AB  - The extracellular electrical response (ocellar potential, OP) and K+ activity
      changes to light were measured in the planarian ocellus by conventional and
      double-barreled ion-selective microelectrodes. The OP evoked by a 0.5 sec light
      flash is a simple monophasic potential, which is sustained during long-term
      illumination. The spectral sensitivity of the OP has the characteristics of a
      rhodopsin with lambda max 505 nm. K+ activity in the extracellular space of the
      ocellus in the dark was 1.1 +/- 0.2 mM (mean +/- SE, n = 6). A 0.5 sec light
      flash and a 120 sec long-term illumination evoked increases in the K+ activity.
      The maximum K+ activity change occurred at 503 nm. These results suggest that the
      efflux of K+ from the planarian photoreceptor into the extracellular space is
      caused by light, and that the OP and the increase of K+ activity are mediated by
      a rhodopsin.

PMID- 8529005
TI  - Proximate, caloric, nitrogen and mineral composition of bodies of some tropical
      bats.
AB  - Proximate (live mass, water, lipid, ash, non-fat organic), caloric, nitrogen, and
      mineral (sodium, potassium, calcium, magnesium, and iron) concentrations and
      total body content of individuals of 24 species of Neotropical and Paleotropical
      bats were determined. Mass-related, concentration patterns were found for all
      measured variables, except iron. Concentrations increase with size for nitrogen,
      calcium, and magnesium but are concave, opening upward, for sodium and potassium.
      These last two elements reach minimal concentrations in bats weighing about 22
      and 28 g dry mass, respectively. Total body content of nitrogen and minerals was
      compared with amounts in similar-sized birds and tetrapodal mammals.

PMID- 8529006
TI  - The gastrointestinal tract of the rock hyrax (Procavia habessinica). 1.
      Morphology and motility patterns of the tract.
AB  - The stomach of the rock hyrax (Procavia habessinica) is divided into a non
      glandular part with very slow movements, and a glandular part which rapidly mix
      the digesta. The large intestine has two fermentation chambers, the caecum, which
      rapidly mixes the digesta, and the colonic sac, which efficiently, but slowly,
      mixes digesta. Between these chambers runs the connecting colon. No retrograde
      transport is observed in any part of the large intestine.

PMID- 8529007
TI  - Lipidemic effect of methanol.
AB  - The effect of methanol on some of the lipid components in serum was studied in
      rats. Methanol was administered by stomach tube in doses of 2 and 6 ml/kg b.wt
      daily for 21 and 6 days, respectively. Methanol was found to accumulate lipids;
      thus, cholesterol, phospholipids and triglycerides increased significantly.
      Concurrently, modification of the lipoid content of organs has been considered.
      It was concluded that methanol and not only formate, is toxic to rats, inspite of
      the alleged difference in routes of its metabolism in primates and rodents.

PMID- 8529008
TI  - Orally administered spermine induces precocious intestinal maturation of
      macromolecular transport and disaccharidase development in suckling rats.
AB  - The effect of orally administered spermine on intestinal cessation in bovine IgG
      transport and digestive enzymes in the small intestine was examined in the
      suckling rats. By the repeated oral administration of spermine (0.1 or 0.25
      mumol/g bwt) for 5 days, the ratio of protein to DNA was significantly increased.
      Maltase and lactase activities changed dose dependently in the spermine treated
      pups. Absorption of bovine IgG transport in the intestine was dose dependently
      depressed by spermine treatments. Morphological inspection of treated pups showed
      a decline in the number of epithelial cells that absorb bovine IgG and in their
      vesicle sizes from basal to upper regions of the villi. The ratio of mitosis in
      the crypt of treated pups significantly increased in the small intestine and
      cecum. These results suggest that exogenously administered spermine induces
      precocious maturation of the macromolecular transmission and disaccharidase
      activity in the small intestine of the suckling rats.

PMID- 8529009
TI  - Ventilatory response to severe acute hypoxia in guinea-pigs and rats with high
      hemoglobin-oxygen affinity induced by cyanate.
AB  - Baseline ventilation, hemoglobin concentration (Hb) and P50 were significantly
      lower in guinea-pigs than in rats. Chronic sodium cyanate (NaOCN) administration
      did not significantly increase hemoglobin concentration in either guinea-pigs or
      rats. It decreased the P50 significantly less in guinea-pigs than in rats. The
      high Hb-O2 affinity experimentally induced did not modify the hypoxic ventilatory
      response (HVR) of guinea-pigs and rats. At the same level of acute hypoxia, HVR
      was significantly lower in NaOCN guinea-pigs than in NaOCN rats. Guinea-pigs,
      genotypically adapted animals to high altitude, displayed relatively minor
      ventilatory and Hb-O2 affinity changes to NaOCN, and a relatively minor HVR to
      acute hypoxia. They probably use tissue and biochemical adaptive mechanisms, in
      addition to their limited extracellular responses to successfully tolerate
      ambient hypoxia.

PMID- 8529010
TI  - Use of monoclonal antibodies for identification of growth-controlling
      neuropeptides in the mussel Mytilus edulis (Mollusca:Bivalvia).
AB  - Monoclonal antibodies were developed against cerebral ganglia (CG) of the mussel
      Mytilus edulis by the immunization of mice with unpurified homogenates of these
      organs. The screening protocol of hybridoma was based upon immunohistological
      observations of cytocentrifugated ganglia cells. A panel of 29 monoclonal
      antibodies (MABs) specific of CG epitopes was harvested and subsequently used for
      the immunocytochemical study of CG cells. Several subpopulations of ganglia cells
      were specifically revealed by MABs. Identification of epitopes involved in growth
      control was approached via the application of a bioassay allowing the assessment
      of protein synthesis stimulation. MAB 42 and 46 affected amino acid incorporation
      induced by CG extract. These results lead to the conclusion that the epitopes
      recognised by these antibodies are involved in growth control. An immunoenzymatic
      assay was performed with CG extracts for quantitative analyses of epitopes.

PMID- 8529011
TI  - Appearance of intraportally infused [15N]urea in blood and urine of domestic
      fowl.
AB  - The time course of the occurrence of intraportally infused [15N]urea in blood and
      urine was investigated in chickens. The infused urea appeared in ureteral urine,
      mostly in the form of urea, as early as 30 min after the start of infusion and
      the excretion further increased up to the end of 2 hr infusion. Blood urea
      concentration rapidly increased and reached about three times the initial level
      at the end of the experiment (P < 0.05 after 20 min), but no significant effects
      were observed on uric acid, ammonia and glutamine concentrations. Fifty-seven
      percent of blood urea N and 3% of blood glutamine-amide N and 1% of blood ammonia
      N, which were determined at the end of experiment, were derived from the infused
      urea N. It is concluded that urea, which is rapidly increased in blood and urine
      after feeding urea to chickens, is mostly derived from dietary urea.

PMID- 8529012
TI  - Differential regulation of vitamin D receptor and intestinal calcium transport
      occurring during sexual maturation in the fowl (Gallus domesticus).
AB  - Quantitative measurements of intestinal vitamin D receptor (VDR) and calcium
      transport taking place in individual villus-attached enterocytes have been
      compared during the onset of sexual maturity to test for a direct involvement of
      VDR in controlling calcium transport across the chick small intestine. Chickens
      of all ages showed VDR to be present in crypt and villus enterocytes, the amounts
      of VDR declining only slightly during enterocyte migration from the crypts to the
      tips of villi. Calcium transport corrected for initial adsorption was lowest in
      the crypt and highest in villus tip enterocytes. These results are consistent
      with VDR initiation and possible later maintenance of calcium transport across
      differentiating enterocytes. The total amount of VDR determined along the crypt
      villus axis was significantly less in immature 11-week-old compared with 17-week
      old sexually mature non-laying and 25-week-old laying chickens. Calcium transport
      was significantly greater in 25-week-old compared with 17- and 11-week-old birds.
      This unexpected up-regulation of VDR in 17-week-old birds was not affected by
      dietary restriction of calcium. Increased VDR expression in 17-week-old sexually
      mature birds is probably initiated by estrogen acting indirectly to increase 1,25
      (OH)2D3 production in the kidney. Increased calcium transport in 25-week-old
      laying chickens could involve estrogen interacting with estrogen receptors as
      well as 1,25 (OH)2D3 interacting with vitamin D receptors to promote gene
      transcription in the intestine.

PMID- 8529013
TI  - High intensity exercise during pregnancy of rats. Effects on mother and
      offspring.
AB  - We see in this study the effect of high intensity exercise (90% VO2 max) in
      pregnant rats and their offspring depending on the length of pregnancy. The
      findings were compared with those obtained for sedentary pregnant rats and non
      pregnant rats for similar exercise. This allowed for analysing the isolated
      effects of exercise (against the sedentary non-pregnant rat control group), of
      pregnancy and of the interaction between the two factors. For checking the effect
      of the length of pregnancy, each group of rats was subdivided into those with
      pregnancy terminated or sacrificed on the seventh, fourteenth or twentieth day of
      the experiment. VO2 max, post-exertion blood lactic acid level, body weight gain,
      food intake, feed efficiency, glucose, triglyceride, total cholesterol, total
      protein and albumin plasmatic concentrations in adult rats, and weight and number
      of offspring of pregnant rats were determined. Pregnancy increased weight gain
      and feed efficiency from the first week of the study, accompanied by a greater
      food intake (from the twelfth day). In the group of pregnant rats subjected to
      exercise, there was a reduction in weight gain percentage and feed efficiency in
      the first and third weeks, staying the same in the second week. A greater food
      intake during the period accompanied this recovery in the second week. In the
      group of non-pregnant rats subjected to exercise, food intake did not vary. As
      the weight gain percentage was less in relation to the non-pregnant control
      group, feed efficiency decreased. Pregnancy induced a drop in blood sugar level
      starting in the second week, and the exercise performed during pregnancy did not
      change this behavior. Pregnancy produced, however, an increase in plasmatic
      concentration of triglycerides and total cholesterol during the third week of
      pregnancy. Exercise performed by pregnant rats also did not change this behavior,
      but the increase observed in the third week was less. Exercise performed by non
      pregnant rats did not change the blood sugar level and plasmatic concentration of
      triglycerides and total cholesterol during the entire experiment. Plasmatic
      concentration of total proteins and albumin showed a drop in the third week of
      pregnancy, probably due to high fetal use of proteins in this stage. Exercise
      performed by the pregnant group caused a lower protein drop in the third week,
      and in the non-pregnant group, determined an increase in plasmatic protein
      concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8529014
TI  - Disaccharidase activities in pregnant and lactating rats.
AB  - The changes in intestinal disaccharidase activities in pregnancy and lactation
      could be explained as a result of an adaptation to the energy demands of each
      reproductive stage. To examine these changes, disaccharidase activities (lactase,
      sucrase, maltase, and trehalase) were measured in the jejunum and ileum of
      virgin, pregnant and lactating Wistar rats. Minor changes in disaccharidase
      activities were observed in pregnancy, whereas an increase of disaccharidase
      activities per small intestine length normalized to body mass was observed in
      lactation.

PMID- 8529015
TI  - Comparison among the effects of oral, intraperitoneal and intravenous fluid
      loading on kidney function and drinking in goats.
AB  - The effects of hyperhydration, induced by oral loading via a stomach tube (41 of
      0.9% NaCl within 2-3 min), intra-peritoneal and intra-jugular infusions (41 of
      0.9% NaCl solution at a rate of 21 hr-1) in normally hydrated goats, on fluid
      retention, plasma expansion, kidney function and drinking response were compared.
      Higher fluid retention (67 and 65% vs. 40% at 3 hr after the termination of the
      infusion, P < 0.01), attenuated diuretic (P < 0.01) and natriuretic (P < 0.01)
      responses and lower expansion of plasma volume (P < 0.05) were recorded in the
      orally and intra-peritoneally treated goats in comparison with the intra
      jugularly treated animals. Portal expansion apparently induces acceleration of
      saliva secretion which recycles water to the gut. Recycling of water to the gut
      reduced excessive expansion of plasma fluid and load on the kidney. Retention of
      water in the rumen satiated the urge to drink in the orally and intra
      peritoneally treated goats for at least 24 hr. The intra-jugularly treated goats
      consumed a significant amount of water (1l), which was approximately half of
      their normal requirement. Under arid conditions, these responses are appropriate
      to the animals' regular exposure to severe dehydration and rapid rehydration.

PMID- 8529016
TI  - The occurrence of artemocyanin in Branchiopoda (Crustacea).
AB  - Artemocyanin, the extracellular hemolymph biliprotein of Artemia, is demonstrated
      in the fairy shrimp Streptocephalus, the clam shrimp Leptestheria and the water
      flea Daphnia. Artemocyanins can be purified from hemolymph as intact polypeptides
      (Mr 170-190,000), but are degraded upon homogenization of the whole animal by
      partial proteolysis to polypeptides with Mr 102,000 and 85,000. The aminoterminal
      sequence of the intact artemocyanin polypeptide was determined, but no clear-cut
      relationships with arthropod biliproteins or other protein families could be
      demonstrated.

PMID- 8529017
TI  - Seasonal patterns in the physiology of the European brown bear (Ursus arctos
      arctos) in Finland.
AB  - The physiological indicators such as body temperature, blood chemistry and
      hematology of seven European brown bears (Ursus arctos arctos) were used in the
      present study. They were kept in either the Zoological Garden of University of
      Oulu (65 degrees N, 25 degrees 24'E) or the Ranua Zoological Garden approx. 150
      km NE of Oulu. Transmitters with a temperature-dependent pulse rate were
      implanted subcutaneously or into the abdominal cavity under anesthesia. Our data
      indicate that the body temperature of the bear decreases during the winter sleep
      to 4-5 degrees C below the normal level (37.0-37.5 degrees C). The lowest values,
      33.1-33.3 degrees C, were measured several times in midwinter. Hematocrit,
      hemoglobin and erythrocyte counts seem to be higher, and the leucocyte count
      lower during the denning period than in the awake bear. Plasma N-wastes were
      lower during the winter sleep than before or after it. The analysed blood
      parameters showed that plasma catecholamines and thyroid hormones decreased in
      the fall.

PMID- 8529018
TI  - Measurement of ventilatory responses in the toad Bufo marinus: a comparison of
      pneumotachography and buccal pressures.
AB  - Determination of pulmonary ventilation in anuran amphibians is usually
      accomplished from recordings of buccal pressure or by pneumotachography.
      Considering the well described changes in ventilatory pattern during increased
      respiratory drive, it is pertinent to determine whether the two methods produce
      comparable ventilatory responses. To resolve this question, a toad was equipped
      with both a buccal cannula and a pneumotachograph enabling a direct comparison of
      the two methods. While the two methods result in similar determinations of the
      overall ventilatory response to hypoxia, there was a poor correlation between
      buccal pressure and exhaled volume for individual breaths.

PMID- 8529019
TI  - Molecular basis for tetrachromatic color vision.
AB  - Determination of the primary structures of six kinds of vertebrate visual
      pigments enabled us to classify them into four groups of cone-type pigments. The
      phylogenetic tree demonstrated that an ancestor of vertebrate visual pigments
      evolved into four kinds of cone-type pigments, from one of which rhodopsins
      diverged. Tetrachromatic color vision of chicken is discussed on the basis of
      both the absorption spectra of purified cone pigments and the filtering effect of
      colored oil-droplets.

PMID- 8529020
TI  - Sea urchin egg tropomyosin isoforms with muscle-type and nonmuscle-type
      antigenicities.
AB  - Egg tropomyosins were prepared from four sea urchin species, Stronglyocentrotus
      intermedius, Anthocidaris crassispina, Hemicentrotus pulcherrimus and
      Pseudocentrotus depressus, and their molecular heterogeneity was investigated by
      electrophoresis and immunoblotting. The molecular heterogeneity of egg
      tropomyosins was species-specific, and two to four kinds of tropomyosin isoforms
      were detected, the apparent molecular weights of which were 29,000-32,000. The
      egg tropomyosin isoforms could be classified into two groups with muscle- and
      nonmuscle-type antigenicities in each species. No obvious difference in their
      cytological localization was observed immunocytochemically in S. intermedius and
      H. pulcherrimus.

PMID- 8529021
TI  - Baboon (Papio ursinus) cathepsin L: purification, characterization and comparison
      with human and sheep cathepsin L.
AB  - Cathepsin L was purified from the liver of a higher primate, the baboon (Papio
      ursinus), largely in a single-chain form and in the form of proteolytically
      active complexes with an endogenous cystatin. This mimics the situation found in
      both human and sheep livers. Both forms of cathepsin L were active at
      physiological pH. Physicochemical characterization and N-terminal amino
      sequencing of baboon cathepsin L showed a close relationship with the human
      enzyme. Cystatins with characteristics similar to those found for stefins A and B
      could also be purified from baboon livers. Proteolytically active, SDS-stable
      complexes could be shown to form in vitro with the molecules characterized as
      stefin B, but not with stefin A type cystatins. The non-inhibitory complexes
      could be shown to require less cysteine for activation than free cathepsin L and
      this, together with the above result, might indicate that a sulfhydryl
      interchange mechanism is responsible for the formation of covalent, non
      inhibitory complexes.

PMID- 8529022
TI  - Species-specific expression of cytochrome c oxidase isozymes.
AB  - Cytochrome c oxidase was isolated from livers and hearts of sheep, dog and
      rabbit, and the polypeptide composition was analyzed by two different SDS-PAGE
      separation systems. The gels were blotted on PVDF-membranes and the N-terminal
      amino acid sequences of the tissue-specific subunits VIa, VIIa and VIII were
      determined in a protein sequencer. Except for subunit VIIa from rat, subunits VIa
      and VIIa from all investigated mammals are tissue-specific expressed in liver and
      heart. In contrast, subunit VIII is clearly different in liver and heart of
      bovine, dog and rat, but identical in liver and heart of human (liver-type),
      sheep, rabbit and also in rainbow trout (heart-type). The data suggest a strong
      species-specific variation of the regulatory properties of cytochrome c oxidase
      in different tissues.

PMID- 8529023
TI  - Odorant-binding proteins of the mouse.
AB  - After the isolation of two odorant-binding proteins (OBP-I and OBP-II) from mouse
      nasal tissue, we have purified two additional OBPs, which bind tritiated 2
      isobutyl-3-methoxypyrazine. OBP-III is a homodimer with subunits of M(r) 22,000
      and pI 4.2. OBP-IV is a homodimer with subunits of M(r) 21,000 and pI 4.85. N
      terminal amino acid sequences indicate that OBP-III is identical in its first 40
      amino acids to the mouse urinary protein, MUP-5, (ii) OBP-IV is > 90% identical
      in its first 30 amino acids to the MUP-4, OBP-II is nearly 80% similar in its
      first 40 amino acids to OBP-I of the rat, and both subunits of OBP-I are > 50%
      identical with hamster aphrodisin.

PMID- 8529024
TI  - Effects of carnosine and related compounds on generation of free oxygen species:
      a comparative study.
AB  - The effect of carnosine and related compounds on the luminol- and lucigenin
      dependent luminescence of rabbit leukocytes, activated by BaSO4, has been
      studied. Carnosine was found to modify BaSO4-induced chemiluminescence of
      leukocytes via suppression of hypochlorous anion generation with simultaneous
      stimulation the system of oxygen superoxide anion. Additionally to this effect
      carnosine prevents enzymic dismutation of O2.. Anserine, acetylanserine, and
      homocarnosine also possess the ability to activate O.2 production by leukocytes.
      The effect is not inherent to imidazole used in the same concentrations.
      Suppression of myeloperoxidase reaction by carnosine and related compounds is
      explained by both inhibiting action on the enzyme itself, and direct
      neutralization of hypochlorous anion due to formation of stable chloroamine
      complexes. Methylation of carnosine at N1 nitrogen of imidazole ring, leading to
      anserine, forced inhibition of myeloperoxidase system, whereas its acetylation at
      the free beta-amino group weakened this effect.

PMID- 8529025
TI  - Allozyme variation in populations of Pleurodema thaul (Lesson, 1826) (Anura;
      Leptodactylidae).
AB  - Genetic variation of 18 loci detected in 13 Chilean and one Argentinian
      population of the toad Pleurodema thaul are described. Seven loci were
      polymorphic in at least one of the studied populations. The average
      heterozygosity values observed for locus went from H = 0.00 for the Las Cardas
      population to 0.114 in the Lautaro locality, with a global average of 5.2%. The
      genetic similarity values gave an average of 0.875 (range 0.726-1.00).
      Accordingly, similarity values were possible to distinguish three groups: north,
      central and Osorno. The Osorno population differed from the central group in Est
      1 and Est-2, yet the Osorno population is only 20 km from a population of the
      central group.

PMID- 8529026
TI  - Evolutionary comparison of enzyme activities of phosphatidylcholine metabolism in
      the nervous system of an invertebrate (Loligo pealei), lower vertebrate (Mustelus
      canis) and the rat.
AB  - While steady-state kinetic parameters (metabolite pools, Km and activation
      energies) are partially known for the enzymes involved in phosphatidylcholine
      synthesis and degradation in mammalian brain, they are not available for the
      nervous system of lower vertebrates or invertebrates. Since the extent of
      evolutionary development of an enzyme is not known a priori, we evaluated the
      kinetic and thermodynamic parameters of choline kinase, CTP:phosphocholine
      cytidylyltransferase, choline phosphotransferase and glycerophosphorylcholine
      phosphodiesterase in squid (Loligo pealei) optic lobe, dogfish (Mustelus canis)
      and rat brain. For all these enzyme activities, basic similarities in Km and
      inhibitor effect were found. The same was true for the activation energies Ea,
      with the exception of squid choline kinase and dogfish cytidylyltransferase.
      Treatment of microsomal membranes with phospholipase C sharply inhibited
      cytidylyltransferase activity in all three animal species. In dogfish brain,
      glycerophosphorylcholine phosphodiesterase activity was undetectable. Our results
      are consistent with the notion that the kinetic properties of the enzyme
      activities leading to the preservation of the phosphatidylcholine membranous pool
      may have appeared early in metazoan evolution and been fully conserved in
      mammals.

PMID- 8529027
TI  - Glycolytic enzymes and assembly of microtubule networks.
AB  - The ability of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), aldolase, pyruvate kinase (PK), and lactate dehydrogenase muscle-type
      (LDH(M)), to generate interactive microtubule networks was investigated. Bundles
      have previously been defined as the parallel alignment of several microtubules
      and are one form of microtubule networks. Utilizing transmission electron
      microscopy, interactive networks of microtubules as well as bundles were readily
      observed in the presence of GAPDH, aldolase, or PK. These networks appear
      morphologically as cross-linked microtubules, oriented in many different ways.
      Light scattering indicated that the muscle forms of GAPDH, aldolase, PK and
      LDH(m) caused formation of the microtubule networks. Triose phosphate isomerase
      (TPI) and lactate dehydrogenase heart-type (LDH(H)), glycolytic enzymes which do
      not interact with tubulin or microtubules, did not produce bundles, or
      interactive networks. Sedimentation experiments confirmed that the enzymes that
      cross-link also co-pellet with the microtubules. Such cross-linking of
      microtubules indicate that the enzymes are multivalent with the capability of
      simultaneous binding to more than one microtubule.

PMID- 8529029
TI  - Effects of cysteamine on pulsatile growth hormone release and plasma insulin
      concentrations in sheep.
AB  - The effects of cysteamine (CSH; 0, 50, or 100 mg/kg BW), a somatostatin depleting
      agent, on growth hormone (GH) and insulin (INS) secretion were studied in sheep
      (Ovis aries). Cysteamine was administered as a single intragastric bolus on day 0
      (0900). Jugular blood samples were collected at 15-min (GH) and 2-hr (INS)
      intervals over an 8-hr period (1100-1900) on day 0, 3, and 7. Intragastric
      administration of CSH at 50 mg/kg BW augmented (quadratic, P = .04) mean plasma
      GH concentration, with the greatest response occurring on day 3. Baseline GH
      concentrations were elevated in wethers dosed with 50 mg/kg BW CSH on day 3,
      whereas wethers dosed with 100 mg/kg BW CSH had lower baseline GH concentrations
      on day 0 (CSH x day interaction, P = .02). Cysteamine administration increased GH
      pulse amplitude (quadratic, P = .15), with the greatest magnigtude of change
      occurring with 50 mg/kg BW CSH on day 0 and 3. Frequency of GH pulses was
      increased (quadratic, P = .10) following CSH treatment. Administration of 100
      mg/kg BW CSH augmented plasma INS on day 0 (CSH x day interaction, P = .09).
      These findings indicate that CSH alters GH and INS secretion in a dose-dependent
      and temporal manner. The observed changes in mean and baseline plasma GH
      concentrations associated with 50 mg/kg BW CSH are consistent with somatostatin
      depletion; however, higher doses of CSH appear to disrupt GH secretion by an
      alternative mechanism.

PMID- 8529028
TI  - Isolation and characterization of the catalytic subunit of protein phosphatase 2A
      from Neurospora crassa.
AB  - The catalytic subunit of protein phosphatase 2A (PP2Ac) was purified from
      Neurospora crassa extract by (NH4)2SO4-ethanol precipitation followed by DEAE
      Sephacel, heparin-Sepharose, and MonoQ chromatography steps about 900-fold to a
      specific activity of 1200 U/g with a 2% yield. The apparent M(r) of PP2Ac was
      estimated to be 35 kDa by gel filtration and 33 kDa by SDS polyacrylamide gel
      electrophoresis. Half maximal inhibition of PP2Ac was achieved at 0.3 nM okadaic
      acid, 0.1 nM microcystin-LR, 56 nM cantharidin and 280 nM endothall
      concentrations. The preparation was completely inhibited by 20 mM NaF, was
      insensitive to rabbit muscle inhibitor-2, and was specific for the alpha-subunit
      of rabbit muscle phosphorylase kinase. According to its biochemical properties,
      N. crassa PP2Ac is very similar to its mammalian counterparts. Antipeptide
      antibodies raised against the N-terminal and C-terminal ends of human PP2Ac did
      not cross-react with N. crassa PP2Ac, indicating sequence differences outside the
      catalytic core of the enzyme.

PMID- 8529030
TI  - A unique strong fibrinolytic enzyme (katsuwokinase) in skipjack "Shiokara," a
      Japanese traditional fermented food.
AB  - Katsuwokinase (KK) is a unique fibrinolytic enzyme recently found in skipjack
      "Shiokara," a Japanese traditional salt-fermented food. A crude enzyme extracted
      from skipjack Shiokara (Katsuwonus pelamis) showed a very strong fibrinolytic
      activity above 45 CU/g (fibrin plate method) based on plasmin. KK not only
      hydrolyzed fibrin but also several synthetic amido substrates, particularly pyro
      Glu-Gly-Arg-pNA. The fibrinolytic activity of KK was not affected in the presence
      of 10% NaCl, was stable in the pH range from 1 to 10 at 37 degrees C for 30 min,
      and was inhibited by DFP, SBTI, BPTI, and aprotinin but not by epsilon-amino-n
      caproic acid and t-4-amino-methylcyclohexane carboxylic acid. The crude enzyme
      contained at least four kinds of KK, and the major form purified had a pI value
      of approximately 5.0 and a molecular weight of 35,000. The N-terminal amino acid
      sequence of 21 residues, I-V-G-G-Y-E-Q-Z-A-H-S-Q-P-H-Q-V-S-L-N-S-G-, had 80%
      homology with that of trypsin. The fibrinolytic activity of the purified enzyme
      was approximately 2.6 times greater than that of plasmin by molar ratio,
      demonstrating its identity as a new and very potent fibrinolytic enzyme.

PMID- 8529031
TI  - Production of an endogenous inhibitor of protein kinase C by embryonic myoblasts
      undergoing differentiation.
AB  - The current studies were undertaken to determine whether embryonic myoblasts or
      myogenic satellite cells undergoing differentiation and fusion contained
      endogenous modulators of protein kinase C (PKC). Clonal-derived turkey embryonic
      myoblast and satellite cell cultures were harvested at confluency and at
      approximately 40% fusion (embryonic myoblasts) or 75% fusion (satellite cells).
      PKC activity in cystosolic preparations of the cells and myotubes was
      undetectable. Cytosolic extracts (0.065 mg protein) of confluent and fused
      satellite cell cultures and confluent embryonic myoblasts had no effect on
      control PKC activity (control: 14.9 pmol/min, control + cytosols: 15.2, 13.9 and
      13.5 pmol/min, respectively). Cytosolic preparations (0.065 mg protein) of
      embryonic myoblast-derived myotubes inhibited control PKC activity (4.0
      pmol/min). In a time-course study, PKC-inhibitory activity was present in
      embryonic myoblasts at the earliest time point examined (30% fusion).
      Additionally, protein phosphatase activity correlated with PKC inhibitory
      activity. Thus, PKC-inhibitory activity appears as embryonic myoblasts begin to
      undergo fusion to form myotubes, but is not present in differentiating satellite
      cells.

PMID- 8529032
TI  - Comparison of trypsin and chymotrypsin from the viscera of anchovy, Engraulis
      japonica.
AB  - The molecular weights of trypsin and chymotrypsin purified from anchovy viscera
      were estimated to be 25.6 and 26.1 Kda, respectively, by SDS-PAGE. Both enzymes
      had their maximal activity at pH 9.0 and 45 degrees C for casein and at pH 8.0
      and 45 degrees C for synthetic substrates. Trypsin hydrolyzed at the position of
      Arg22 and Lys29, and chymotrypsin did at the position of Phe1, Tyr16, Phe24,
      Phe25, and Tyr26 of insulin beta-chain. The K'm and kcat of trypsin were 50
      microM and 1.84 microM-1 min-1 toward N-benzoyl-L-arginine-p-nitroanilide (BAPNA)
      and those of chymotrypsin were 89 microM and 10.0 microM-1min-1 toward N-succinyl
      (Ala)2-Pro-Phe-p-nitroanilide. The activation energy of trypsin and chymotrypsin
      were estimated to be 14 Kcal/mol toward N-benzoyl-L-arginine-p-nitroanilide and
      6.5 Kcal/mol toward benzoyl-L-tyrosine ethyl ester.

PMID- 8529034
TI  - Genetic determinants of dopaminergic activity: potential role in blood pressure
      regulation.
AB  - Dopamine (DA) availability for precursor function and peripheral biological
      action is dependent on synthesis and inactivation enzymes, most of them have been
      cloned and located. An aromatic acid decarboxylase (AADC) defect has been
      reported in male homozygotic twins. The syndrome of complete dopamine-beta
      hydroxylase deficiency with orthostatic hypotension and very high DA contributes
      to our understanding of the role of DA as a catecholamine with a peripheral
      biological action of its own. X-linked isolated monoamine oxidase A gene
      deficiency represents a marked disturbance of monoamine metabolism. The genes of
      the two major extraneuronal DA-metabolizing enzymes--catechol-O-methyl
      transferase and phenolsulfotransferase (PST)-have also been defined. Of
      particular interest is a bidirectional shuttle system between the PST and
      sulfatase which have been cloned and located. DA, highly sulfoconjugated via PST,
      yields DA sulfate which is reconvertible by sulfatase to Free DA. A defect of
      sulfatase catalyzing this process results in a predominance of DA as biologically
      inactive DA sulfate and so attenuates the DA action. Enzymatic defects of DA
      synthesis and metabolism are thus genetic modulators of DA action.

PMID- 8529033
TI  - Immunoglobulin A levels in southern elephant seal (Mirounga leonina) milk during
      the suckling period.
AB  - Immunoglobulin A (IgA) levels in milk samples from southern elephant seals at
      King George Island, Antarctica are reported. IgA levels were determined
      throughout the suckling period (approximately 23 days). The IgA concentration in
      southern elephant seal milk was lower than in other mammals and, unlike most
      mammalian milk, was not high during early lactation. There was not a definite
      pattern in IgA levels, which fluctuated within narrow limits throughout the
      suckling period (mean +/- SD, 30.81 +/- 6.38 mg IgA/100 g milk). If IgG was
      present, its level was too low to be detected by the method used. This is the
      first evidence in Southern elephant seal of the possibility of transmission of
      passive immunity after birth involving secretion of IgA in the milk.

PMID- 8529035
TI  - Proceedings of the 5th International Conference on Peripheral Dopamine. Kyoto,
      Japan, October 20-22, 1994.

PMID- 8529036
TI  - Physiological significance of plasma sulfoconjugated dopamine: experimental and
      clinical studies.
AB  - Sulfoconjugated catecholamines have been regarded simply as metabolites of free
      catecholamines. However, a conjugated form of the catecholamine, dopamine has
      recently attracted much attention because it is present at high levels in the
      plasma of humans and experimental animals. We carried out experimental and
      clinical studies to determine the physiological significance of this large amount
      of dopamine conjugate in the plasma. Clinical studies showed that the plasma
      level of dopamine sulfate decreased significantly during the acute phase of heart
      failure, whereas that of free dopamine increased. Moreover, the plasma level of
      conjugated dopamine in patients with essential hypertension was higher than that
      in control subjects, and being highest in patients with renal hypertension. In
      experimental studies, we examined the activity for deconjugating DA sulfate in
      homogenates of organs from dogs. The kidney and liver exhibited the highest
      activities, and in the heart, the activity was higher in the atrium than the
      ventricle. We also examined the effect of dopamine sulfate on isolated perfused
      rat heart. Dopamine sulfate was found to be converted to free dopamine, which was
      responsible for the positive inotropic action, in atrial tissue. Moreover,
      deconjugation of DA sulfate to the free form was accelerated by a high work lord
      on the heart. From these results, we conclude that the formation of dopamine
      sulfate plays a role in regulating the level of plasma free dopamine and that
      plasma dopamine sulfate may be a storage or reserve form of dopamine. Free (or
      active) dopamine may be formed through a deconjugation reaction when necessary.

PMID- 8529037
TI  - Dopaminergic modulation of physiological and pathological neurohumoral activation
      in man.
AB  - Close relations exist between the peripheral dopaminergic system, and the
      sympathetic nervous and renin-angiotensin-aldosterone system: D1 dopamine
      receptor stimulation-induced vasodilation may activate the sympathetic nervous
      and renin-angiotensin system in vivo, presynaptic D2 dopamine receptor
      stimulation is known to inhibit stimulated norepinephrine release from
      sympathetic nerve terminals, in experimental conditions both in vitro and in
      vivo. Endogenous dopamine has a tonic inhibitory effect on aldosterone release.
      Conversely, basal sympathetic activity has been found to be required for the
      natriuretic effect of dopamine in proximal renal tubules. Other relations include
      the conversion of dopamine to other catecholamines, and co-release. This review
      considers the reflection of some of these relations and their clinical
      significance in man in physiological and pathophysiological conditions,
      especially congestive heart failure. An inhibitory effect of the nonselective
      dopamine agonist ibopamine on plasma norepinephrine levels was found in normal
      man during exercise but not at rest, and in patients with several degrees of
      congestive heart failure, both at rest and during exercise. Infusions of dopamine
      1 microgram/kg/min, but not 3 micrograms/kg/min were found to lower plasma
      norepinephrine levels during sympathetic stimulation by exercise or by a cold
      pressor test in normal man. Dopamine antagonists enhance the rise in plasma
      norepinephrine levels during exercise, indicating that endogenous dopamine also
      inhibits norepinephrine release. Both phentolamine and prazosin abolish the
      natriuretic effects of dopamine in man, even when the renal hemodynamic effect of
      dopamine is unaffected. In conclusion, it is important to be aware of clinically
      significant interactions between the peripheral dopaminergic and sympathetic
      nervous system at different levels.

PMID- 8529038
TI  - Cloning of the dopamine-1A (D1A) receptor gene expressed in porcine renal
      epithelial cells.
AB  - We sought to determine the molecular identify of the dopamine-1 (D1) receptor
      expressed in the porcine renal epithelial cell line LLC-PK1. We first isolated a
      partial cDNA by the reverse transcription-polymerase chain reaction procedure and
      then used the partial cDNA to isolate positive overlapping clones from a porcine
      genomic DNA library. Sequence analysis of the gene revealed that the longest open
      reading frame encoded a 446 amino acid protein that was 95% identical to the
      human D1A receptor. Expression studies in mammalian cells were also consistent
      with the clones encoding a D1 receptor. Northern blot hybridizations with LLC-PK1
      poly (A+) RNA were strongly positive. The porcine D1A gene has two exons and a
      short intron in the 5' untranslated region. The 5' flanking region lacks a TATA
      and CAAT box but is high in GC content (68%) and contains multiple Sp1 binding
      sites. The 5' flanking region also contains numerous other cis-acting elements
      for transcription factors. These results indicate that the D1A receptor is the
      major D1 receptor expressed in LLC-PK1 cells and further suggest that LLC-PK1
      cells may be a useful model to study the regulation of renal D1A receptor gene
      transcription.

PMID- 8529039
TI  - Suppression of noradrenaline spillover by the dopamine prodrug gamma-L-glutamyl-L
      dopa: a central effect?
AB  - The DA prodrug gamma-L-glutamyl-L-dopa (gludopa) has a high degree of renal
      selectivity with 2-step conversion to DA in the kidney. The effects of gludopa,
      with and without DA-2 receptor blockade, on renal and total noradrenaline (NA)
      spillover, were studied in two groups of rabbits. Eight rabbits received gludopa
      infusion (25 and 100 micrograms/kg/min and 8 received an infusion of gludopa and
      DA-2 receptor antagonist, YM-09151 (50 micrograms/kg i.v.). Renal and total NA
      spillover rates were measured by 3H-NA tracer method before and after gludopa
      infusion. Brain NA, DA, gludopa and L-dopa content were measured after gludopa
      infusion in 5 rabbits; control values for tissue catecholamine and drug levels
      were obtained in 5 untreated rabbits. Gludopa infusion markedly increased kidney
      DA content (300-fold) and DA excretion (6000-fold) but had little effect on
      plasma DA. It produced a dose-related fall in mean (+/- SEM) renal NA spillover
      (21.6 +/- 3.7 to 10.6 +/- 2.7, 7.2 +/- 2.7 ng/min, p < 0.01). Even greater falls
      were observed in total NA spillover after gludopa (43.1 +/- 10.2 to 19.7 +/- 3.4,
      9.4 +/- 1.8 ng/min, p < 0.01). DA-2 receptor antagonism had no influence on the
      effects of gludopa on either renal or total NA spillover. Significant amounts of
      gludopa were detected in the brain after drug infusion (0.28 +/- 13 nmol/g brain
      tissue). Gludopa, a putative renal selective dopamine prodrug with effects
      mediated via DA-1 receptors also significantly inhibits both renal and extra
      renal NA spillover. This effect is not a DA-2 effect but may be mediated
      centrally.

PMID- 8529040
TI  - Effects of dopaminergic drugs on the sympathoadrenal system.
AB  - Several studies have suggested that dopamine (DA) plays a major role in
      cardiovascular functions. Dopaminergic receptors have been found on sympathetic
      nerve terminals (DA2), kidney (DA1, DA2), vascular smooth muscle (DA1) as well as
      on sympathetic ganglia (DA1, DA2) and adrenal gland (DA1, DA2). Previous studies
      have shown that DA2 receptor stimulation by a specific DA2 agonist, quinpirole
      (1) elicits a peripheral depressor action (decreased blood pressure) and a
      central pressor component involving an increase in both sympathetic tone and
      vasopressin release and (2) does not affect under in vivo conditions adrenal
      catecholamine release. The present study investigates the effects of fenoldopam,
      a specific DA1 receptor agonist on both cardiovascular responses and
      catecholamine release from the adrenal medulla. In conscious normal dogs,
      fenoldopam (10, 20 and 40 micrograms/kg i.v.) elicited a decrease in blood
      pressure and a marked increase in heart rate associated with a rise in plasma
      catecholamine levels. The increase in heart rate is only due to baroreflex
      mechanism since fenoldopam (conversely to DA2 receptor agonists like quinpirole)
      does not exert a central excitatory component (as shown by the absence of
      cardiovascular effects after intracisternal injection). Moreover, in sinoaortic
      denervated dogs (i.e. animals deprived from baroreflex pathways), the decrease in
      arterial blood pressure was more important than in normal dogs. Heart rate was
      unchanged. In these animals, DA1 stimulation induced a decrease in sympathetic
      tone, as shown by the significant fall in plasma noradrenaline levels. These "in
      vivo" data clearly demonstrate the inhibitory role of ganglionic DA1
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529041
TI  - Dopaminergic activity and endorenal dopamine synthesis in non-insulin dependent
      diabetes mellitus.
AB  - In the present study we tried to clarify the differences of the cardiovascular
      and renal responses to feeding in relation to the peripheral dopamine system. In
      control subjects (C), ingestion of protein (100 g) induced an increase in Ccr
      accompanied by an increase in tubular sodium excretion (FENa+). Patients with non
      insulin dependent diabetic (NIDDM), a protein-induced increase in Ccr was
      comparable to that in C, while FEN+ did not change following protein. Since an
      increase in urinary 3,4-dihydroxyphenylacetic acid was blunted in NIDDM, an
      impaired natriuretic response to high protein may be results from an insufficient
      synthesis of renal dopamine. Plasma dopamine and its metabolites in NIDDM
      following protein tended to be greater than in C. Protein induced a greater
      decrease in blood pressure (BP) in NIDDM, but no increase in pulse rate was
      observed. An ordinary diet containing 10 g of protein also induced a decrease in
      BP. A reflex tachycardia was observed in C and normotensive NIDDM but not in
      hypertensive one. In normotensive NIDDM, plasma dopamine and norepinephrine
      increased after the diet, while in hypertensive NIDDM there were no increases in
      catecholamines. From these results it is suggested that the relatively elevated
      peripheral dopaminergic activity and the blunted dopamine synthesis in the kidney
      may be responsible for the abnormal cardiovascular and renal responses to feeding
      in patients with NIDDM.

PMID- 8529042
TI  - Pathophysiological role of dopamine in the kidney: effects in diabetes mellitus
      and after contralateral nephrectomy.
AB  - Both insulin-dependent diabetes mellitus (IDDM) and unilateral nephrectomy (UNX)
      are associated with an increase in the glomerular filtration rate. Glomerular
      hyperfiltration has been linked to intraglomerular hypertension in both
      conditions, although it has only been linked to the development of nephropathy in
      diabetes. In this study, we examined the possibility of preventing diabetic
      nephropathy through early dopamine (DA) prodrugs treatment and we also
      investigated the participation of endogenous DA in the acute functional
      adaptation of the remaining kidney after UNX. In an animal model of IDDM
      (steptozotocin-treated Wistar rats), the early increase in the glomerular
      filtration rate was prevented by treatment with DA prodrugs (L-dopa or gludopa),
      an effect which was mimicked by fenoldopam (a D1 agonist) and suppressed by
      carbidopa and SCH 23390 (a D1 antagonist). An increase in endorenal DA synthesis
      and the subsequent stimulation of vascular D1 receptors appears to prevent early
      glomerular hyperfiltration in diabetic rats. However, in a long-term study
      lasting more than one year, streptozotocin-diabetic Wistar rats (unlike to
      diabetic Munich Wistar rats) failed to develop overt nephropathy characterized by
      albuminuria and systemic hypertension. During long-term treatment of diabetic
      rats with L-dopa, the renal availability of DA was diminished. The acute
      adaptation of the remaining kidney to UNX took the form of an early transient
      pressor effect with a moderate increase in the glomerular filtration rate and
      renal blood flow, and a marked decrease in tubular sodium reabsorption. SCH 23390
      suppressed the hemodynamic and tubular responses to UNX, suggesting that
      endogenous DA plays a key role.

PMID- 8529043
TI  - Different mechanisms of renal Na-K-ATPase regulation by dopamine in the proximal
      and distal nephron.
AB  - We reported a novel intracellular mechanism of renal Na-K-ATPase regulation by
      dopamine (DA) in the rat cortical collecting duct (CCD), which involves
      stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). In the present
      experiments we determined whether this mechanism also operates in other nephron
      segments. In the medullary thick ascending limbs (MTAL), DA and other cAMP
      agonists inhibited Na-K-ATPase activity, an effect that was abolished by PKA
      inhibitor IP20, but various protein kinase C (PKC) activators did not, analogous
      to our previous findings in CCD. In sharp contrast, DA inhibition on Na-K-ATPase
      in the proximal convoluted tubule (PCT) was reproduced by PKC agonists. These
      effects was blocked by PKC inhibitor staurosporine, but not by IP20. Mepacrine, a
      PLA2 inhibitor, reversed the pump effect of all agents, and arachidonic acid (AA)
      produced a dose-dependent pump inhibition, in all three nephron segments. We
      conclude that the intracellular mechanisms of Na-K-ATPase regulation by dopamine
      differ in the proximal and distal nephron, as they involve stimulation of PKA in
      MTAL and CCD, and of PKC in PCT. These two pathways probably share a common
      mechanism in stimulating PLA2 and AA release in both regions of the nephron.

PMID- 8529044
TI  - DA1 receptor-mediated renin release from isolated rat glomeruli.
AB  - The present study was performed in order to examine the effects of dopamine (DA)
      on renin release and to clarify which subtype of DA receptor, DA1 or DA2
      contributes to renin release. Male Wistar rats aged seven weeks were used.
      Glomeruli were isolated by the modified Beierwaltes' sieving method and were
      transferred to a sealed chamber and superfused with Krebs-Ringer solution. In the
      first experiment, the changes in renin release induced by DA and the effects of a
      non-selective DA antagonist, haloperidol and a beta antagonist, propranolol on DA
      induced renin release were examined. In the second experiment, the effect of a
      DA2 receptors antagonist, spiperone and of a DA1 receptor antagonist, SCH-23390
      on renin release were investigated. Basal levels of renin release were 2.46 +/-
      0.36 ng ATI/h/10(4) glomeruli (mean +/- SEM). DA caused a dose-dependent increase
      in renin release. The renin release induced by DA was inhibited by haloperidol
      but not by propranolol. The maximum level of renin release induced by 10(-5)M DA
      was 4.13 +/- 0.63 ng ATI/h/10(4) glomeruli. SCH-23390 at 10(-5)M caused
      significant suppression of DA-induced renin (p < 0.05). In contrast, 10(-5)M
      spiperone failed to suppress DA-induced renin release. These results suggest that
      DA induced renin release from isolated glomeruli through the DA1 receptors.

PMID- 8529045
TI  - Renal dopamine spillover rate using 3H-dopamine radiotracer technique as an index
      of renal dopaminergic nerve activity.
AB  - Renal and total dopamine (DA) spillover rates at rest were measured in 25
      conscious rabbits with chronically implanted renal vein catheters. Renal DA
      spillover rate was calculated from veno-arterial difference in plasma free DA
      concentrations across the kidney corrected by the fractional extraction of
      infused 3H-DA. Plasma free DA concentrations were 11.0 +/- 2.7 pg/ml in the
      artery and 14.3 +/- 3.6 in the renal vein. Renal and total DA spillover rates
      were 0.51 +/- 0.08, 2.61 +/- 0.30 ng/min, respectively, both of which were
      significantly (p < 0.001) lower than the respective norepinephrine (NE) spillover
      rates (renal: 16.3 +/- 1.4, total: 39.6 +/- 1.7). The fractional extraction of 3H
      DA across the kidney (55 +/- 3%) and the total DA clearance (285 +/- 31 ml/min)
      were both significantly (p < 0.05) higher than that of 3H-NE (45 +/- 3) and the
      total NE clearance (198 +/- 9), respectively. The ratio of renal to the total
      spillover rate of DA (0.23 +/- 0.05) was significantly (p < 0.05) lower than that
      of NE (0.41 +/- 0.04). These results demonstrate that DA is released into plasma
      within the kidney and suggest that the measurement of renal DA spillover rate
      using 3H-DA radiotracer technique is useful to detect resting renal dopaminergic
      nerve activity.

PMID- 8529046
TI  - Dopamine tonically modulates natriuresis in the saline-expanded dogs.
AB  - Dopamine (DA) has been shown to be an endogenous catecholamine that promotes
      natriuresis by activating tubular DA receptors, but its role on natriuresis
      appears to be equivocal, and the precise mechanisms and signaling pathway of
      multiple DA's receptor subtypes are not yet clarified. We used low dose of DA
      intravenously in saline (S) volume-expanded dogs to see the alterations in
      natriuresis. The results showed that there is a critical dose that induces no
      enhancement of natriuresis of volume expansion, and that the lower and higher
      doses of DA produced relatively larger natriuresis. Pretreatment of
      metoclopramide (MCP) in this settings caused even higher and significant
      increases of natriuresis. In conclusion, DA seems to determine tonically the
      level of natriuresis in saline-expanded dogs. DA may exert a dual effect on
      signal transduction pathways such that one leading to antinatriuresis with high
      affinity and the other to natriuresis with low affinity signaling cascades for
      DA. MCP may block the antinatriuretic limb of the signaling pathway.

PMID- 8529047
TI  - Comparison of dopamine contents in lung vasculature of several species.
AB  - Catecholamine contents of human, rabbit and rat pulmonary vasculature were
      surveyed. Human pulmonary vasculature was obtained from lobectomized specimens of
      lung tumors. Catecholamines were measured by high performance liquid
      chromatography after aluminum extraction. High dopamine (DA) content (1.4 nmol/g
      wet weight) and high DA/noradrenaline (NA) ratio (17.9%) were observed in rabbit
      pulmonary arterial trunks. In rabbit pulmonary arterial branches, DA content was
      0.26 nmol/g wet weight and DA/NA ratio was 4.2%. In rat, NA contents were less in
      intra- and extra-pulmonary arteries (1.5 and 4.0 nmol/g wet weight, respectively)
      compared with pulmonary vasculature of rabbit or with the other vasculatures of
      the same animals. DA contents were 1.9 and 1.8 nmol/g wet weight in intra- and
      extra-pulmonary arteries, respectively, and DA/NA ratios were markedly high (218
      and 48%, respectively). On the other hand, DA/NA ratios were around 1% in human
      intrapulmonary arteries and that for large-sized (more than 2 mm in diameter)
      intrapulmonary vein was 8.5%. Species difference and regional difference among
      pulmonary vascular beds are evident and at least in human pulmonary artery, DA/NA
      ratio is not as high as rabbit and rat pulmonary arteries.

PMID- 8529048
TI  - Localisation of dopamine D1-like and D2-like receptors in the pulmonary
      vasculature.
AB  - The pharmacological profile and the anatomical localisation of dopamine receptor
      subtypes were investigated in the rabbit pulmonary vascular bed using combined
      radioligand binding and light microscope autoradiography techniques. Dopamine D1
      like receptor sites, which probably belong to the dopamine D1 receptor subtype,
      were characterized in sections of lung using [3H]-SCH 23390 as a ligand. These
      sites were located within the tunica intima and the tunica media of large sized
      intrapulmonary artery branches and in the tunica media of medium sized
      intrapulmonary artery branches. Dopamine D2-like receptor sites, which probably
      belong to the dopamine D2 receptor subtype, were characterized using [3H]
      spiroperidol as a ligand. These sites were located within the tunica adventitia
      of both extra- and intrapulmonary artery branches. Dopamine D2-like receptor
      sites were also found in the tunica adventitia of the human pulmonary artery, but
      not of the rat pulmonary artery. The different anatomical localization of
      dopamine D1 and D2 receptor subtypes in the pulmonary vasculature suggests that
      these sites are involved in the modulation of pulmonary vascular tone by
      interacting with different receptors unevenly distributed throughout the
      pulmonary vascular bed.

PMID- 8529049
TI  - Does dopamine act on myocardial cells?
AB  - We examined the electrophysiological effects of dopamine on the single myocardial
      cells isolated from the rat and rabbit heart. Dopamine at a concentration of 1 or
      10 microM did not affect the L-type Ca2+ current (ICa) or the transient outward
      current (ITO) in rat ventricular, rabbit atrial, ventricular, and sinoatrial node
      cells. It did not induce any detectable change in the action potential
      configuration of the rabbit ventricular cells either. We conclude that dopamine
      does not directly act on myocardial cells at least in terms of the
      electrophysiological properties.

PMID- 8529050
TI  - Plasma free and sulfoconjugated dopamine before and after a half-marathon.
AB  - To elucidate whether increased plasma levels of free dopamine (F-DA) after
      exercise are due to deconjugation of sulfoconjugated (S-) DA in plasma, we
      compared the changes in plasma F- and S- DA, as well as changes in both the S-
      and F- forms of epinephrine (E) and norepinephrine (NE), after running a half
      marathon. Free catecholamines (F-CAs) were measured by automated high-performance
      liquid chromatography (HPLC). Total (F+S) CAs were determined using an efficient
      deconjugation method as follows; 1200 microliters plasma was incubated with 152
      mU arylsulfatase (AS) for 30 min at pH 7.6. The plasma levels of F-CA (pg/ml)
      (mean +/- SEM) all increased significantly (p < 0.01) after the half-marathon;
      i.e., F-DA increased from 13.3 +/- 5.7 to 176.3 +/- 32.2; F-E from 58.0 +/- 12.3
      to 764.3 +/- 136.4; F-NE from 246.6 +/- 15.2 to 3082.0 +/- 690.3. OF S-CAs, S-E
      (from 127.8 +/- 26.0 to 1218.2 +/- 190.8) and S-NE (from 717.1 +/- 61.6 to 5586.9
      +/- 761.9) also increased, but, in contrast, among the S-CAs, only the increase
      in S-DA (from 5324.9 +/- 1967.3 to 7359.6 +/- 1627.9) was not statistically
      significant. Sulfoconjugation may play an important role in inactivating F-DA as
      well as F-NE and -E, that are released into plasma in response to vigorous
      exercise. Thus, plasma F-DA is unlikely to be derived through deconjugation of
      plasma S-DA.

PMID- 8529051
TI  - Cardiotoxicity of catecholamines after application of L-DOPA in Wistar-Kyoto
      (WKY) and spontaneously hypertensive rats (SHR).
AB  - In order to estimate the role of the sympatho-adrenal system as a trigger in
      cardiovascular mortality risk after L-DOPA administration in patients with
      Parkinsons disease we performed the following experiments in normotensive Wistar
      Kyoto-rats (WKY) and spontaneously hypertensive rats (SHR). L-DOPA was given
      orally in increasing doses (30, 100, 300 mg/kg b.w.). Haemodynamic parameters
      (BP, HR) were measured by tail cuff plethysmography and catecholamine
      concentrations in tissues assayed by high pressure liquid chromatography.
      Stressful situations were induced by experimental myocardial infarction. After
      administration of L-DOPA a dose-dependent increase in blood pressure in both WKY
      and SHR was observed with a prolongation in SHR. Significantly increased
      concentrations of dopamine in the hearts were measured in both strains.
      Noradrenaline stores in the heart of WKY were more filled than in the heart of
      SHR. Only in SHR high adrenaline concentration in the adrenal medulla were
      measured after L-DOPA administration. Circulating adrenaline concentrations were
      significantly enhanced after myocardial infarction in WKY and could be further
      elevated by pretreatment with L-DOPA. From the results obtained it is concluded
      that L-DOPA administration in WKY and SHR leads to exaggerate synthesis and
      massive release of catecholamines and in consequence to an enhanced
      cardiovascular mortality risk due to cardiotoxicity of catecholamines. It can be
      extrapolated that increased cardiovascular mortality risk seen in Parkinson
      patients treated with L-DOPA and benzerazide is probably associated with
      increased synthesis and release of catecholamines during stressful situations.

PMID- 8529052
TI  - Pituitary adenylate cyclase-activating polypeptide stimulates the synthesis of
      dopamine in cultured bovine adrenal chromaffin cells.
AB  - The effect of pituitary adenylate cyclase-activating polypeptide1-38 (PACAP1-38)
      on the synthesis of dopamine in cultured bovine adrenal chromaffin cells was
      examined. PACAP1-38 stimulated [14C]dopamine synthesis from [14C]tyrosine, in a
      concentration-dependent manner, causing maximal stimulation at 10(-7)M. This
      stimulatory action of PACAP1-38 was not significantly inhibited by staurosporine
      (an inhibitor of protein kinase C) or in the cells in which protein kinase C was
      down-regulated by prolonged exposure to TPA (an activator of protein kinase C),
      whereas it was partially attenuated in Ca(2+)-free medium. PACAP1-38 increased
      the formation of [3H] inositol phosphates, [Ca2+]i, 45Ca2+ uptake and cAMP level.
      The peptide also stimulated the phosphorylation of tyrosine hydroxylase, the
      enzyme catalyzing the rate-limiting step in dopamine synthesis. Dopamine
      synthesis and tyrosine hydroxylase phosphorylation stimulated by the maximal
      effective concentration of dibutyryl cAMP or high K+, which activates Ca2+
      uptake, were further enhanced by PACAP1-38. These results indicated that PACAP1
      38 may stimulate the activities of cAMP- and calcium-dependent protein kinases in
      cultured bovine adrenal chromaffin cells, resulting in increase in the synthesis
      of dopamine probably by stimulation of phosphorylation of tyrosine hydroxylase.

PMID- 8529053
TI  - D-1 dopamine receptors mediate dopamine-induced pancreatic exocrine secretion in
      anesthetized dogs.
AB  - Characterization of dopamine (DA) receptor subtypes was examined on the canine
      exocrine pancreas using selective DA receptor agonists and antagonists in
      anesthetized dogs. Each drug was injected i.a. in a single bolus fashion. Graded
      doses of DA (0.01-3 mumol) produced dose-dependent increases in the secretory
      rate of pancreatic juice, with a maximum effect at approximately 1 mumol.
      SCH23390 (3-30 nmol), a selective D-1 DA receptor antagonist, caused a
      progressive parallel shift to the right in the dose-response curve for DA-induced
      pancreatic secretion without changes in the maximal response. However,
      domperidone (3 mumol), a selective D-2 DA receptor antagonist, did not antagonize
      the DA-induced pancreatic exocrine secretion. A Schild analysis of the data
      indicates that the inhibitory constant value for SCH23390 to inhibit DA
      stimulated secretion was 6.9 nmol. In addition, the stimulatory effects of
      SKF38393 (0.1-10 mumol) and YM435 (0.3-30 nmol), selective D-1 DA receptor
      agonists, and LY171555 (1-10 mumol), a selective D-2 DA receptor agonist, on
      pancreatic secretion were demonstrated. The rank order of agonist potency was
      YM435 > DA > SKF38393 >> LY171555. These results suggest that DA-induced
      pancreatic exocrine secretion is mediated by activation of D-1 DA receptors.

PMID- 8529054
TI  - Effects of acute levodopa administration on blood pressure and heart variability
      in never treated parkinsonians.
AB  - The effects of levodopa on autonomic nervous system (ANS) were investigated
      through the measurement of blood pressure (BP) and heart rate (HR) variability in
      15 de novo parkinsonian who never received dopaminergic drugs. BP and HR were
      obtained using digital photoplethysmography in supine and standing positions.
      Measurements were achieved 90 min after administration, in a double blind cross
      over way, of placebo or levodopa (200 mg)+benserazide (50 mg). Spectral analysis
      was performed using fast Fourier transformation (FFT) on 512 consecutive SBP and
      HR values. Spectral modulus was integrated for calculation of total spectra and
      of low frequency (LF: 66-129 mHz) or high frequency band (HF: respiratory
      frequency +/- 50 mHz). After placebo, orthostatism was followed by a significant
      increase in BP and HR whereas relative variabilities in LF and HF remained
      unchanged. After levodopa, BP was significantly lower in supine position without
      changes in HR and LF. During orthostatism, changes observed in BP and in FFT were
      similar to those observed during placebo period. These data indicate that
      levodopa reduces supine and standing BP but does not impair orthostatic
      adaptation. This effect is not due to modification of BP or HR variability and
      appears to independent of any direct effect on ANS.

PMID- 8529055
TI  - Gene expression of aromatic L-amino acid decarboxylase mRNA in the kidney of
      normotensive and hypertensive rats.
AB  - Peripheral dopamine (DA) synthesis and release increase during hypertensive stage
      of spontaneously hypertensive rats (SHR). DA is generated from 3,4
      dihydroxyphenylalanine by L-amino acid decarboxylase (AADC). We have studies
      urinary DA and DA metabolites and the gene expression of neuron and non-neuron
      specific AADC mRNA in the kidney of SHR. Compared to Wister-Kyoto rats (WKY),
      there was an increased urinary free DA and DOPAC excretions in 8 and 12 week-old
      SHR. At the age of 16 weeks, the difference in free DA excretion between SHR and
      WKY rats disappeared, although the urinary DOPAC excretion remained significantly
      higher in SHR, but urinary HVA excretion did not differ from WKY rats. The
      expression of the neuron specific AADC mRNA in the kidney of SHR and WKY rats was
      not detected, but the non-neuron specific AADC mRNA in the kidney of SHR and WKY
      rats was detected. The gene expression of the non-neuron specific AADC mRNA
      tended to decrease with age in SHR. The results suggest that a decrease in renal
      DA production with age may be caused by diminished expression of non-neuron
      specific AADC mRNA in kidney.

PMID- 8529056
TI  - Dopamine deficiency--its potential contribution to chronic renal failure
      complicating hypertension.
AB  - Baseline dihydroxyphenylalanine (DOPA) and dopamine (DA), their respective
      sulfates as well as oral DOPA administration-induced changes were compared in age
      and blood pressure-matched hypertensive patients without and with moderate
      chronic renal failure (CRF) and control subjects. The only common feature of both
      hypertensive groups was a defective DA generation from DOPA. Hypertensive
      patients with moderate CRF were distinct from those without, having increased
      basal concentrations of plasma DOPA and DA sulfates. After oral DOPA
      administration, plasma and urinary DOPA sulfate rose while renal DA sulfate
      clearance was decreased. Possible enzymatic defects contributing to CRF-induced
      increases of DOPA and DA sulfates and their potential role in perpetuating renal
      failure via glomerular hypertension are discussed.

PMID- 8529057
TI  - Involvement of renal dopaminergic system in experimental neurogenic arterial
      hypertension.
AB  - The effect of chronic salt loading (10 g of NaCl for a period of 7 days) on
      urinary dopamine release has been investigated in 3 groups of beagle dogs:
      normotensive dogs (group 1: n = 7), and 2 groups of dogs made hypertensive by
      chronic sinoaortic denervation [group 2: (n = 6) during the first 4 months after
      sinoaortic denervation i.e. a model of arterial hypertension with high levels of
      plasma catecholamines and group 3: (n = 6) one year after denervation i.e. a
      model of arterial hypertension with normal sympathetic tone]. In normal dogs
      (group 1), salt loading induced an increase in urinary dopamine excretion during
      the two first days after salt loading. The rise in urinary dopamine was blunted
      in group 2. It was not observed in group 3. Salt loading failed to change
      arterial pressure and heart rate in the three groups of animals. These data show
      an alteration of the renal dopaminergic system in hypertensive sinoaortic
      denervated dogs suggesting that a dopaminergic impairment can appear during the
      development of arterial neurogenic hypertension.

PMID- 8529058
TI  - Studying the dopaminergic system with transfected receptors.
AB  - Dopamine receptors are responsible for diverse effects within and outside the
      central nervous system. The five dopamine receptors that have been cloned (D1A,
      D1B also known as D5, D2, D3, and D4) belong to two major families; the D1 like
      and D2 like dopamine receptors. The D1 like receptors are linked to the
      stimulation while D1 like receptors are linked to the inhibition of adenylyl
      cyclase. The physiologic role of the dopamine receptors has been difficult to
      decipher because several of the subtypes co-exist in the same tissue. However,
      studies of receptors artificially expressed using transfected cDNA have revealed
      some of the biochemical mechanisms unique to each dopamine receptor subtype.

PMID- 8529059
TI  - Urinary excretion of free dopamine and digoxinlike substances correlates with
      endogenous secretion of insulin in normotensive adults, but not in hypertensive
      subjects.
AB  - We investigated whether urinary excretion of free dopamine is related with the
      humoral factors which affect Na+, K+ ATPase activity in the kidneys. Subjects
      were 51 adults admitted in a hospital without renal insufficiency: they were
      divided into normotensive (n = 36, 60 +/- 3 years old, 122 +/- 3/73 +/- 2 mmHg)
      and hypertensive groups (n = 15, 65 +/- 5 years old, 157 +/- 6/91 +/- 2 mmHg).
      Urinary excretion of free dopamine was significantly and positively correlated
      with urinary excretion of C-peptide immunoreactivity of insulin (CPR) (r = 0.451,
      p = 0.014) in normotensive subjects, but not in hypertensive subjects (r = 0.155,
      p = 0.668). Urinary excretion of endogenous digoxinlike substances (EDLS) was
      also significantly and positively correlated with urinary CPR (r = 0.500, p =
      0.006) in normotensive subjects, but not in hypertensive subjects (r = 0.275, p =
      0.363). In normotensive subjects, urinary excretion of free dopamine and EDLS may
      be regulated at least in part by insulin secreted endogenously. In hypertensive
      subjects, however, this regulatory mechanism of the diuretic factors, such as
      insulin, EDLS and dopamine, is thought to be deranged, which might result in
      decompensation of a diuretic and antidiuretic balance leading to blood pressure
      elevation.

PMID- 8529060
TI  - Renal dopaminergic activity in patients with primary aldosteronism.
AB  - To clarify the role of renal dopaminergic activity in patients with primary
      aldosteronism (PA), urinary excretion of free dopamine (DA) and the conversion
      ratio of DA from l-dopa in the kidney were investigated in 8 patients with PA and
      10 normotensive subjects (NT). All subjects were hospitalized and received a
      standard diet (Na 120 mEq, K 75 mEq/day) and 2 h renal clearance test was
      performed. Plasma l-dopa concentration (p-DOPA), creatinine clearance (Ccr),
      urinary excretion of sodium (UNaV) and DA (uDA) as well as fractional excretion
      of sodium (FENa) were measured. No significant difference was found in UNaV or
      FENa between NT and PA, or between before and after adrenalectomy (Adx) in PA.
      UDA was significantly higher in PA than NT, and decreased significantly after
      Adx. There was no difference in the product of Ccr X p-DOPA between NT and PA, or
      between before and after Adx in PA. The ratio of uDA/(Ccr X p-DOPA) was
      significantly higher in PA than NT. After Adx this ratio decreased significantly
      to the normal range. These results suggest that (1) renal dopaminergic activity
      is augmented and contributes to the escape phenomenon in PA, and (2) augmented
      renal DA production in PA might be caused by an increase of conversion to DA from
      l-dopa at the renal proximal tubules.

PMID- 8529062
TI  - Postprandial changes in noradrenergic and dopaminergic activity in patients with
      essential hypertension.
AB  - In order to elucidate the role of noradrenergic and dopaminergic activity in the
      pathogenesis of postprandial hypotension, the effect of feeding of ordinary diet
      on blood pressure, pulse rate, plasma catecholamine and other circulating
      vasoactive substances such as insulin were examined in mild essential
      hypertensive patients (EH) and their age-matched control subjects (N). Mean blood
      pressure significantly decreased in both N and EH after feeding, and the decrease
      tended to be greater in EH than in N. Feeding induced a marked increase in plasma
      norepinephrine in both N and EH. Plasma dopamine significantly increased
      following feeding was observed in N, while the increase in plasma dopamine
      following feeding was blunted in EH. The ratio of norepinephrine to dopamine
      following in EH was significantly greater than that in N. From these results, it
      is suggested that the feeding-induced stimulation of noradrenergic activity may
      be a result from the decrease in blood pressure, and that the blunted response of
      dopaminergic activity in EH may reflect the enhanced conversion of dopamine to
      norepinephrine probably due to the enhanced activity of dopamine beta-hydroxylase
      in the sympathetic nerves.

PMID- 8529061
TI  - Effect of dexamethasone on plasma free dopamine: dopaminergic modulation in
      hypertensive patients.
AB  - To investigate the peripheral dopaminergic modulation in the pathogenesis of
      human hypertension, we examined the responses of plasma free dopamine (DA) to
      dexamethasone (Dx) administration, which is suggested to activate dopaminergic
      activity. We administered Dx 2 mg intravenously to patients with primary
      aldosteronism (PA), essential hypertension (EH), and normotensive controls (NT).
      Plasma free DA was increased significantly in all groups and the responses were
      more remarkable in PA than in EH and NT. Plasma epinephrine (E) showed a gradual
      increase while plasma norepinephrine (NE) tended to decrease in all groups. The
      responses of both plasma DA and E were completely blocked by 250 mg of alpha
      methyl-p-tyrosine, a tyrosine hydroxylase (TH) inhibitor, suggesting that Dx may
      stimulate peripheral dopaminergic activity by increasing catecholamine
      synthesizing enzyme (probably TH) activities. These data suggest that DA itself
      plays an inherent role in the sympathoadrenal regulation rather than only as a
      precursor of NE and that dopaminergic hyperresponses may be involved in the
      pathophysiology of PA.

PMID- 8529063
TI  - Hormonal mechanisms in blood pressure reduction during hemodialysis in patients
      with chronic renal failure.
AB  - To elucidate the hormonal mechanisms of blood pressure (BP) reduction during
      hemodialysis in patients with chronic renal failure (CRF), we performed this
      study using 7 normotensive (NT) and 17 hypertensive (HT) patients who were
      strictly matched in age, body weight, body weight gain from the last HD, and
      duration of HD. Blood pressure, pulse rate, plasma norepinephrine (NE), and
      plasma dopamine levels were used as indices of sympathetic nerve activity,
      before, at 50% of hemodialysis (HD) and at 100% of HD (at the end of HD) on the
      third day after the last HD. As hemodialytic BP reduction was defined as BP
      decline of more than 10% in pre-HD mean BP, in normotensive patients with CRF,
      hemodialytic BP reduction was recognized in 0/7 (0%) at 50% of HD and 4/7 (57%)
      at 100% of HD, and in hypertensive patients it was recognized in 3/17 (18%) at
      50% of HD and 4/17 (24%) at 100% of HD. Percentile changes in plasma NE levels
      increased slightly following hemodialysis in normotensive patients with
      hemodialytic BP reduction and in hypertensives without BP reduction, while those
      in normotensives without BP reduction and in hypertensives with BP reduction did
      not change. However, percentage changes in plasma dopamine (DA) levels decreased
      significantly at the end of HD (NT; p < 0.05, HT; p < 0.01) following
      hemodialysis in both normotensive and hypertensive patients with hemodialytic BP
      reduction, while changes in patients without BP reduction, percentage changes in
      DA did not change (patients with BP reduction vs. patients without BP reduction).
      In conclusion, hemodialytic BP reduction may be predisposed by abnormal
      sympathetic nerve responsiveness.

PMID- 8529064
TI  - Free and total dopamine in human plasma: effects of posture, age and some
      pathophysiological conditions.
AB  - Although dopamine (DA) has an important role also outside the central nervous
      system, the physiological significance of DA in the peripheral plasma is not
      clearly known. In the present study, we assayed the levels of free and total
      (free plus conjugated) DA in the human plasma to examine the effect of posture,
      age and some pathophysiological conditions. Nine healthy volunteers were
      subjected for head up tilt study. For the examination of the effect of age and
      some pathophysiological conditions, venous blood samples were taken after
      overnight fast in 64 control subjects who have no obvious disease and patients
      who had essential hypertension or congestive heart failure (CHF). The plasma free
      adrenaline (AD), noradrenaline (NA) and DA were determined by a HPLC
      diphenylethylenediamine method and total DA was determined by the same HPLC
      method after acid hydrolysis. After tilting neither free nor total DA changed
      significantly despite the increased plasma AD and NA levels. Plasma free NA, DA
      and total DA levels were correlated positively with age in control subjects but
      not in the hypertensive nor CHF patients. Patients with CHF showed higher levels
      of plasma free AD, NA and DA and freeDA/totalDA ratio than did in control
      subjects. We suspect that plasma DA increased with age partially due to change in
      renal catecholamine handling and cardiac function.

PMID- 8529065
TI  - 3,4-dihydroxyphenylalanine (DOPA) decarboxylase deficiency and resultant high
      levels of plasma DOPA and dopamine in unfavorable neuroblastoma.
AB  - Neuroblastoma (NB) is a tumor which arises from neural crest cells. In the
      developing neural crest cells, the induction of 3,4-dihydroxyphenylalanine (DOPA)
      decarboxylase is more delayed than that of tyrosine hydroxylase and dopamine-beta
      hydroxylase. If NB cells are arrested in an early stage of neural crest
      development, the induction of DOPA decarboxylase is insufficient and the
      accumulation and secretion of DOPA can be caused. The biochemically immature
      phenotype is thought to represent the undifferentiated characteristics of the
      cells and might correlate with the grade of malignancy. To investigate whether
      the hypothesis is clinically applicable or not, we have measured plasma DOPA,
      dopamine and urinary catecholamine metabolites in NB patients. The levels of
      plasma DOPA, dopamine, urinary homovanillic acid (HVA) and vanillactic acid (VLA)
      were significantly higher in patients with unfavorable NBs and the higher plasma
      DOPA level was significantly associated with the patients' age (> 1 year old),
      tumor stage (III, IV) and DNA diploidy. Serial determination of plasma DOPA was a
      good monitor of the disease course. These results are compatible with the
      hypothesis on DOPA decarboxylase deficiency and DOPA secretion in
      undifferentiated, unfavorable NBs. In conclusion, the plasma DOPA can be used to
      predict patients' prognosis as well as to follow up patients with NB.

PMID- 8529066
TI  - Metabolism of dopamine prodrug, docarpamine.
AB  - Docarpamine is a dopamine prodrug which has been selected from a large number of
      dopamine derivatives in order to develop an orally effective dopamine. The
      pharmacokinetics and metabolism after oral administration of docarpamine were
      studied in rats and dogs. The maximum concentration of free dopamine in plasma
      after oral administration of docarpamine to rats and dogs was 13 and 4-6 times,
      respectively, higher than those of dopamine (DA). In the first pass metabolism
      study in dogs, the main metabolic pathways after oral administration of
      docarpamine were catechol ester hydrolysis in the small intestine, and amide
      hydrolysis and conjugation in the liver. Conversion rates from docarpamine to DA
      in various rat tissue homogenates were in the order of the liver > small
      intestine > blood. The concentrations of DA conjugate and 3,4
      dihydroxyphenylacetic acid in plasma after oral administration of DA to dogs were
      higher than those of docarpamine. This result indicates that protected groups of
      the docarpamine molecule suppress the first pass metabolism of orally
      administered dopamine. In conclusion, the findings of this study suggest that
      docarpamine can be used as an oral dopamine prodrug. The main first pass
      metabolism after oral administration of docarpamine are catechol ester hydrolysis
      in the small intestine, and amide hydrolysis and conjugation in the liver. Free
      dopamine, which is a pharmacologically active form, is mainly produced in the
      liver.

PMID- 8529067
TI  - The role of renal dopamine in the reduction of high blood pressure by beta 1
      selective beta-blocker with intrinsic sympathomimetic activity in spontaneously
      hypertensive rats.
AB  - The present experiments were undertaken to clarify the difference of renal
      dopamine production from beta 1-selective beta-blocker with and without intrinsic
      sympathomimetic activity (ISA). Either beta-blocker with ISA, celiprolol (100 or
      300 mg/kg/day; CEL-100 or CEL-300) or beta-blocker without ISA, atenolol (50
      mg/kg/day; ATE-50) was administered to the SHR from 19 to 26 weeks. Degrees of
      lowering blood pressure in CEL-300 SHR and in ATE-50 SHR were similar, but
      decrease in heart rate was significantly less in CEL-300 SHR than in ATE-50 SHR.
      Urine output, which was significantly less in control SHR than in control WKY,
      was significantly greater in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR.
      Urinary excretions of noradrenaline (u-NA) and dopamine (u-DA) were significantly
      higher in control SHR than in control WKY and a comparable u-DA/u-NA ratio was
      found in these two groups. U-DA and the ratio of u-DA/u-NA were significantly
      elevated in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. There was a
      significant positive correlation between u-DA/u-NA ratio and urine output and a
      significant negative correlation between the ratio of u-DA/u-NA and change of
      blood pressure in control SHR, CEL-100 SHR and CEL-300 SHR. These results suggest
      that an enhancement of renal dopamine production by ISA (beta 2 stimulation) of
      beta 1-selective beta-blocker may contribute, at least in part, to the
      antihypertensive effect of this drug.

PMID- 8529068
TI  - The effects of different doses of dopamine and domperidone on increases of plasma
      norepinephrine induced by cold pressor test in normal man.
AB  - The effect of dopamine 1 and 3 micrograms/kg/min i.v., of dopamine 1 and 3
      micrograms/kg/min i.v. combined with domperidone 30 mg per os and of placebo
      infusion on plasma norepinephrine concentration before and during sympathetic
      stimulation by a cold pressor test was investigated in 10 healthy volunteers (1
      female, 9 males, mean age 28, range 19-41). Dopamine 1 microgram/kg/min resulted
      in a blunting of the rise in plasma norepinephrine concentration during the cold
      pressor test, compared with placebo infusion. The addition of domperidone to
      dopamine 1 microgram/kg/min abolished this effect. Plasma norepinephrine levels
      during dopamine 3 micrograms/kg/min infusion, both with and without domperidone,
      were not different from placebo, but significantly higher compared to dopamine 1
      microgram/kg/min infusion. Dopamine 1 and 3 micrograms/kg/min infusion, both with
      and without domperidone resulted in a blunted increase in blood pressure compared
      to placebo infusion. Dopamine 1 microgram/kg/min infusion resulted in a lower
      systolic blood pressure during the cold pressor test compared to dopamine 3
      micrograms/kg/min infusion. No significant changes in heart rate occurred during
      the cold pressor test comparing the different circumstances. We conclude that in
      healthy volunteers only dopamine 1 microgram/kg/min, but not dopamine 3
      micrograms/kg/min, blunts the increase in plasma norepinephrine concentration
      during a cold pressor test; this effect is abolished by pretreatment with
      domperidone. We presume that for dopamine 1 microgram/kg/min the inhibitory
      effects of presynaptic DA-2 receptor or alpha-2 adrenoceptor stimulation on
      plasma norepinephrine concentration predominate. When dopamine 3
      micrograms/kg/min is infused, the inhibitory effects might be counteracted by
      uptake-1 inhibition or enhanced synthesis and release of norepinephrine, either
      directly or indirectly.

PMID- 8529069
TI  - Pharmacological characterisation and autoradiographic localisation of dopamine
      receptor subtypes in the cardiovascular system and in the kidney.
AB  - Combined radioligand binding and light microscope autoradiography techniques were
      used for investigating the pharmacological profile and the microanatomical
      localisation of dopamine receptor subtypes in the cardiovascular system and in
      the kidney. In superior mesenteric and renal arteries the predominant dopamine D1
      like receptor belongs to the D5 (or D1b) subtype. This site is located within
      smooth muscle of the tunica media. The same receptor subtype predominates in the
      kidney, where it has a vascular and tubular localisation. The dopamine D2-like
      receptor subtype expressed by systemic arteries belongs to the D2 receptor
      subtype. It has a prejunctional and endothelial localisation. In the kidney the
      predominating dopamine D2-like receptor belongs to the dopamine D3 subtype. Atria
      but not ventricles express dopamine D2-like receptors belonging to the D4
      receptor subtype. The above results suggest that in spite of the emerging
      complexity of the dopamine receptor profile demonstrated by molecular biology
      techniques, radioligand binding and autoradiographic techniques, if performed
      with appropriate radioligands and/or in the presence of compounds active on
      specific receptor subtypes, may represent a useful tool for better understanding
      the biological significance of peripheral dopamine receptors.

PMID- 8529070
TI  - Vascular dopamine-I receptors.
AB  - The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth
      muscle cells by phorbol ester, glucocorticoid and sodium chloride was studied.
      The extent of [3H]Sch-23390 binding to phorbol ester-treated cell was increased
      without any change in the dissociation constant (Kd). At a concentration of 10
      nmol/l, the synthetic glucocorticoid dexamethasone increased maximum receptor
      binding (Bmax) but had no effect on the Kd. 100 mmol/l sodium chloride did not
      change Bmax, but increased the Kd for DA1 receptor. The production of cAMP in
      response to DA1 receptor stimulation was enhanced without any change of the
      adenylate cyclase activity. The glucocorticoid effect on DA1 of arterial smooth
      muscle cells became apparent after hours of incubation in the presence of the
      steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) and
      by the glucocorticoid receptor antagonist RU-38486, indicating that the effect
      required protein synthesis through glucocorticoid receptors. Treatment of cells
      with 1 mumol/l dexamethasone for 24 h increased basal and DA1-stimulated
      adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium
      chloride in a dose-dependent manner. These results suggest differential control
      of DA1 receptors on vascular smooth muscle cells by protein kinase C,
      glucocorticoid or sodium chloride.

PMID- 8529071
TI  - Comparison of the effect of dopamine in primate arteries and veins.
AB  - Mechanical responses to dopamine of isolated human and monkey veins were
      isometrically measured and compared to those of the arteries. Human
      gastroepiploic and monkey mesenteric veins responded to dopamine with
      contractions, whereas the arteries in the same region responded with relaxations.
      Treatment with phentolamine converted the venous contraction to a relaxation,
      which was not influenced by propranolol but was abolished by droperidol. The
      relaxation was endothelium-independent and converted to a contraction by SCH23390
      but unaltered by domperidone. Dopamine increased the cyclic AMP content in the
      human veins. Monkey vena cava and portal vein did not respond to dopamine with
      relaxation even under alpha-adrenoceptor blockade. It is concluded that primate
      veins and arteries from the gastric and mesenteric regions respond quite
      differently to dopamine; the alpha-adrenoceptor-mediated contraction predominates
      over the relaxation mediated via D1-receptor in the veins, and vice versa in the
      arteries. In monkey large veins, dopamine receptor does not appear to play a
      functional role. The veno-constrictor action of dopamine, together with actions
      on myocardium and resistance vessels, would contribute to increasing of the
      cardiac output.

PMID- 8529072
TI  - Dopamine D1 receptor regulation of phospholipase C.
AB  - Dopamine is an endogenous catecholamine which exerts its actions by occupancy of
      specific receptors. Dopamine receptors are classified into two main groups: the
      two cloned D1-like receptors (D1A and D1B in rats; D1B is also known as D5 in
      humans) are linked to stimulation of adenylyl cyclase, while the three cloned D2
      like receptors (D2 or D2A, D3 or D2B, D4 or D2C) are linked to inhibition of
      adenylyl cyclase. All these dopamine receptors originally cloned from the brain
      are expressed in tissues outside the central nervous system including the kidney.
      Dopamine regulates many cellular activities, including transmembrane ion
      transport. Activation of D1-like receptor decreases sodium transport by cAMP
      dependent and cAMP independent mechanisms. Dopamine, via D1-like receptors, may
      inhibit Na+/H+ exchange activity in renal brush border membranes by a cAMP
      independent/Gs alpha-linked mechanism. Another cAMP independent pathway of sodium
      transport inhibition is mediated by phospholipase C, which has several isoforms
      (PLC beta, PLC gamma, and PLC delta with several members in each). Catecholamines
      stimulate expression and activity of phospholipase C isoforms in a concentration,
      time, and receptor-dependent as well as regional and subcellular compartmental
      specific manner. In renal cortical membranes, intrarenal administration of
      norepinephrine for 3-4 h increases PLC beta expression and activity but has no
      effect on PLC gamma activity. In contrast, intrarenal administration of a D1
      agonist for 3-4 h increases PLC beta 1 but decreases PLC gamma expression and
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529073
TI  - Dopaminergic modulation of Na,K-ATPase activity in the proximal tubules of
      normotensive and hypertensive rats.
AB  - Renal proximal tubular Na,K-ATPase plays an important role in the maintenance of
      sodium homeostasis and it is known that dopamine (DA) exerts an inhibitory effect
      on the activity of this enzyme. We have found that DA-induced inhibition of Na,K
      ATPase is abolished in the spontaneously hypertensive rats (SHR) in comparison
      with age-matched Wistar-Kyoto (WKY) rats. Dopamine inhibits Na,K-ATPase via
      phospholipase C coupled protein kinase C pathway. The enzyme protein kinase C
      subsequently causes inhibition of Na,K-ATPase. In the SHR, DA-induced activation
      of phospholipase C is diminished, which in turn is responsible for the abolished
      inhibition of Na,K-ATPase. We have now shown that DA-induced activation of
      protein kinase C, which results from activation of DA-1 receptors is also
      abolished in the SHR which would account for the failure of DA to inhibit Na,K
      ATPase in the hypertensive animals. Recently, we have examined the possibility
      that the failure of DA to inhibit Na,K-ATPase activity may be related to abnormal
      expression of DA receptors. In radioligand binding studies with [3H] SCH 23390 as
      a DA-1 receptor ligand and [3H] spiroperidol as a DA-2 receptor ligand we showed
      that both [3H] SCH 23390 and [3H] spiroperidol bindings are best fit to one site
      model in either WKY or SHR. Both Bmax and KD of either ligand binding to proximal
      tubule in the SHR were not statistically different from their WKY
      counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529074
TI  - Studies on the nature of the antagonistic actions of dopamine and 5
      hydroxytryptamine in renal tissues.
AB  - The present work examines the possibility of whether the reciprocal effects of
      dopamine (DA) and 5-hydroxytryptamine (5-HT) are only dependent on the
      antagonistic nature of the signal resulting from the activation of their specific
      receptors or may also result from a competitive type of inhibition at different
      levels of the synthetic and metabolic pathways shared by DA and 5-HT. Studies
      performed in isolated proximal convoluted tubules (PCT) have shown that L-5-HTP
      and L-DOPA use the same transporter in order to be taken up into the cell and
      both L-DOPA and L-5-HTP exert a competitive type of inhibition upon their
      cellular uptake. The decrease in the formation of 5-HT in isolated PCT induced by
      L-DOPA reflects most probably a reduction in the intracellular availability of L
      5-HTP. However, in experiments conducted in homogenates of PCT L-DOPA was found
      to be a better substrate for AAAD than L-5-HTP. Apart from sharing a common
      synthetic pathway, DA and 5-HT also share a common metabolic pathway; type A
      monoamine oxidase (MAO-A), the predominant form of MAO in rat renal tissues,
      converts DA into 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-HT into 5
      hydroxyindolacetic acid (5-HIAA). However, in contrast to 5-HT, DA can be
      metabolized by MAO-B and catechol-O-methyltransferase. Inhibition of MAO-A was
      found to produce a 2-fold increase in the urinary excretion of 5-HT; this
      increase in the urinary excretion of 5-HT was accompanied by an unexpected
      reduction in the urinary excretion of DA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529075
TI  - The role of renal natriuretic depressor systems on hypertensive mechanisms in
      reduced renal mass hypertensive rats.
AB  - The pathophysiological role of renal natriuretic depressor systems and endogenous
      digitalis like factor (EDLF) on blood pressure (BP) elevation was studied in
      reduced renal mass rats (RRM) with saline loading for a model of volume dependent
      hypertension. Fifty-four male Sprague-Dawley rats were operated on to remove
      varying proportions of their kidney mass (5/6 RRM, n = 13; 4/6 RRM, n = 16; 3/6
      RRM, n = 12) or sham operated (control, n = 13). They were given 1% saline to
      drink for 4 weeks. BP was elevated significantly at the 1st week in 5/6 RRM and
      continued to increase until the 4th week, but this was not seen in the other 3
      groups. Urine volume (UV) and urinary sodium excretion (UNaV) increased after
      saline loading in all groups. Urinary kallikrein excretion was significantly
      lower in order of the 5/6, 4/6 and 3/6 RRM at the basal state and after saline
      loading. A significant negative correlation was observed between urinary
      kallikrein and BP. Urinary PGE2 was increased in each RRM in order of the 5/6,
      4/6 and 3/6 RRM groups. A significant positive correlation was observed between
      urinary PGE2 and BP, UV or UNaV. The basal urinary DA excretion was significantly
      lower in 3 RRMs than in the control. After saline drinking, urinary DA increased
      in 3 RRMs, while differences disappeared in the control and RRMs. Urinary EDLF
      increased immediately after the initiation of saline loading in all groups,
      except the control group, and returned to the basal level 2 weeks later in 3/6
      and 4/6 RRM. Only in 5/6 RRM, the urinary EDLF remained higher than the basal
      level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529076
TI  - Dopaminergic regulation of aldosterone secretion: its pathophysiologic
      significance in subsets of primary aldosteronism.
AB  - Although aldosterone (Aldo.) secretion is regulated by various humoral factors,
      evidence has accumulated to support an involvement of dopaminergic system in its
      regulation. The pathophysiological significance of the dopaminergic system in
      primary aldosteronism (PA) however remains unknown. In the present study, we
      examined the effects of metoclopramide (MCP) on Aldo. secretion in normal
      subjects (n = 11) and patients with essential hypertension (EH, n = 8),
      aldosterone-producing adenoma (APA, n = 10), and idiopathic hyperaldosteronism
      (IHA, n = 6). Plasma Aldo., prolactin (PRL), renin, cortisol, serum sodium, and
      serum potassium levels were determined before and 30 min after i.v. bolus
      injection of 10 mg MCP at 9 a.m. Plasma Aldo. showed a significant increase after
      MCP in normal subjects, EH, and APA, but not in IHA. The incremental response of
      plasma Aldo. was largest in APA and smallest in IHA. The percentage increase in
      plasma Aldo. from the basal level was significantly attenuated in IHA, while no
      significant difference was seen among other groups. Although plasma PRL showed a
      significant increase in response to MCP, no difference of the change was seen
      among the groups. There was no significant change in plasma cortisol, renin,
      serum sodium, and serum potassium levels in response to MCP. In addition, the
      response of Aldo. to MCP was normalized in APA after unilateral adrenalectomy,
      while that of PRL did not change. These results indicate that the adrenal
      dopaminergic activity is enhanced in APA and attenuated in IHA and suggest an
      involvement of the dopaminergic system in the pathogenesis of IHA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8529077
TI  - Plasma free dopamine: physiological variability and pathophysiological
      significance.
AB  - Dopamine (DA) is the most abundant catecholamines in human plasma and exists
      mostly in the sulfo-conjugated form (DA sulfate), a biologically inactive
      metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its
      physiological significance. However, PDA, when measured with a highly sensitive
      radioenzymatic method, showed quite different features from norepinephrine and
      epinephrine in some types of clinical hypertension, lower in essential
      hypertension and higher in primary aldosteronism and pheochromocytoma. There was
      a weak but significant correlation between the values of PDA and DA sulfate
      measured in the same specimens, but DA sulfate was more susceptible to impaired
      renal function. Upright posture, high salt diets and an intravenous injection of
      metoclopramide (MCP, 10 mg), a DA receptor antagonist, induced a slight but
      significant increase in PDA in normal and hypertensive subjects. An intravenous
      dexamethasone (2 mg) caused a gradual increase in PDA over 150 min after
      medication, which was completely blocked by concomitant administration of alpha
      methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The responses of PDA to both
      high salt diets and MCP were blunted in salt-sensitive patients with
      uncomplicated essential hypertension. The results suggest that DA is not only a
      precursor of norepinephrine biosynthesis but also plays an inherent role as an
      active neurotransmitter in the peripheral sympathoadrenal system, and that PDA is
      a sensitive marker of peripheral dopaminergic activity, which may operate to
      modulate the cardiovascular and endocrine functions and participate in the
      pathogenesis of some types of hypertension.

PMID- 8529078
TI  - Activation of renal dopamine system by physical exercise.
AB  - Physical exercise is one of the life-style modifications used for lowering blood
      pressure. Except for diminished norepinephrine spill over, the mechanism by which
      physical exercise exerts its effects was not known. Based on our preliminary
      finding that the reduction of blood pressure was inversely correlated to the
      baseline plasma renin activity, we have consequently revealed that mild exercise
      reduces plasma volume and hence the cardiac index. In order to elucidate the
      mechanism, we have investigated all possible parameters relevant to plasma volume
      regulation. Among them, urinary free dopamine and urinary active kallikrein
      increased in the early stages (weeks 2-4) while atrio-natriuretic factor (week 4)
      and endogeneous ouabain-like substance (EOLS) consequently (weeks 7-10)
      decreased. Serum taurine increased and plasma norepinephrine decreased in the
      late stages. The conclusion reached is that mild exercise seems to first activate
      the renal dopamine and kallikrein systems and second trigger other mechanism,
      such as an increase in taurine and decreases in EOLS and norepinephrine.

PMID- 8529079
TI  - Role for endogenous dopamine in modulating sympathetic-adrenal activity in
      humans.
AB  - Dopamine (DA) is synthesized and secreted in central as well as peripheral
      nervous system and in the adrenal medulla. Neuronal DA receptors, which have been
      characterized as D2 receptors, mediate an inhibition of adenylate cyclase and are
      located prejunctionally on sympathetic nerve endings and on chromaffin cells.
      Their pharmacological activation causes an inhibition of in vitro and in vivo
      norepinephrine (NE) release from sympathetic nerve terminals and an inhibition of
      in vitro epinephrine (E) release from the adrenal medulla. Endogenous DA, co
      secreted with the other catecholamines (CA), modulates sympathetic-adrenal
      discharge only during high sympathetic stimulation through an autocrine
      mechanism, limiting excessive sympathetic adrenal discharge. Also
      pheochromocytoma cells synthesize and express D2 receptors. In patients with
      pheochromocytoma D2 antagonists cause hypertensive crises but the mechanism
      mediating this effect is still unknown as well as whether endogenous DA might
      modulate tumoral secretion.

PMID- 8529080
TI  - Diagnostic significance of dopamine estimation using plasma and urine in patients
      with adrenal and renal insufficiency, renal transplantation and hypertension.
AB  - Although free and conjugated dopamine (DA) constitute most of the plasma and
      urine catecholamine pool, the diagnostic significance of DA estimation for the
      evaluation of illness is not clear. We evaluated the clinical utility of DA
      estimation by measuring free and conjugated DA in patients with various illness.
      Patients with adrenal insufficiency did not show decreases in DA concentrations
      but did demonstrate reductions in free and conjugated plasma adrenaline (Ad).
      Patients with established stage of essential hypertension exhibited decreased
      plasma concentrations of free and conjugated DA, although they were
      hyperadrenergic. In patients with chronic renal insufficiency and failure, the
      free DA concentration in the urine decreased depending on the severity of renal
      impairment. Conversely, plasma concentrations of conjugated DA are higher in
      patients with chronic renal failure than in normal subjects. The high plasma
      concentrations of conjugated DA decreased dramatically following hemodialysis and
      renal transplantation. Urinary free DA excretion increased markedly following
      renal transplantation. In conclusion, the estimation of the free and conjugated
      DA in plasma and urine is clinically useful for the diagnosis of adrenal
      insufficiency, essential hypertension, and renal insufficiency and failure. It
      also can be used to monitor the effectiveness of hemodialysis and renal
      transplantation.

PMID- 8529081
TI  - Is there a third peripheral catecholaminergic system? Endogenous dopamine as an
      autocrine/paracrine substance derived from plasma DOPA and inactivated by
      conjugation.
AB  - In mammals, the sympathetic neurotransmitter is norepinephrine (NE), and the main
      adrenomedullary hormone is epinephrine (EPI). The sources and physiological roles
      of the third endogenous catecholamine, dopamine (DA), outside the brain have been
      obscure. Several lines of evidence suggest that in the periphery, rather than DA
      serving only as the precursor for the active compounds, released from sympathetic
      nerves and the adrenal medulla, DA may also act as an autocrine/paracrine
      regulator of local organ function. Thus, in the kidneys, most of DA formation
      appears to be from proximal tubular uptake of plasma DOPA, and binding of locally
      formed DA to dopaminergic receptors decreases Na/K ATPase activity and thereby
      accentuates natriuresis. In the gastric mucosa, DA may modulate sodium absorption
      and acid secretion. Recent clinical and laboratory animal evidence has indicated
      that the lungs and mesenteric organs contribute substantially to total body
      production and metabolism of DA. Generation of DA in non-noradrenergic, non
      adrenergic cells can explain why human urine contains higher concentrations of DA
      and its metabolites than of NE and its metabolites. The vast preponderance of
      plasma DA in humans is sulfoconjugated. Since patients with sympathoneural
      failure have normal plasma levels of DA sulfate, one may speculate that the
      sulfoconjugating mechanism is relatively independent of sympathetic nerves and
      acts to localize DA effects and inactivate DA entering the circulation. These
      considerations lead to the concept of a third peripheral catecholaminergic
      system, where DA derived from plasma DOPA acts as an autocrine/paracrine
      substance and is inactivated by conjugation.

PMID- 8529082
TI  - A healthy lifestyle is the treatment of choice for obesity in coronary patients.

PMID- 8529083
TI  - A review of heart rate and blood pressure responses in the cold in healthy
      subjects and coronary artery disease patients.
AB  - Despite methodological differences in the limited number of studies reviewed, it
      appears that cardiovascular responses at rest and during exercise in the cold
      differ between patients with CAD and healthy subjects (Figures 1 and 2). This
      difference remains, even when attempting to control for investigation time and
      conditions. Typical exercise time reported for patients with CAD exercising in
      the cold is 4 to 8 minutes, where HR and SBP are generally the same or higher.
      Data corresponding to a similar time frame (5-15 minutes) in healthy subjects
      show HR to be lower or no different, whereas SBP was similar in both studies.
      Logically, healthy subject's RPP values would be similar or lower in the cold,
      which may be a teleological development to conserve myocardial oxygen uptake in
      the face of elevated sympathetic stimulation during cold exposure. The lower HR
      would offset the cold-induced hypertension and also help to preserve cardiac
      output. In healthy subjects, cardiac output is similar in the cold despite a
      higher stroke volume (SV) due to the lower HR. However, the similar cardiac
      output reported by Epstein and colleagues in patients with CAD, both at rest and
      during exercise at 15 degrees C, was obtained by increases in SV and HR. A
      blunted peripheral vasoconstriction response in older subjects could lead to
      reduced central blood volume with a corresponding decrease in venous return and
      SV. An inability to maintain an appropriate SV in the cold by patients with CAD
      may be responsible for the elevated HR to maintain cardiac output. However, in
      healthy subjects, SV appears to have a triphasic response.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8529084
TI  - Breathing retraining in chronic obstructive pulmonary disease.

PMID- 8529085
TI  - Exercise intensity increased by addition of handheld weights to rebounding
      exercise.
AB  - PURPOSE: Researchers who studied the effects of rebound exercise on fitness have
      concluded that the intensity of rebound exercise elicited only minimal
      improvements in fitness. This study determined how the addition of arm pumping
      with handheld weights (HHW) would increase exercise intensity while rebounding.
      METHODS: Fifteen male subjects (20 to 43 years) ran in place on a mini-trampoline
      at a stride frequency of 120 foot strikes per minute, with the sole of the foot
      15 cm above the rebounder rim. Oxygen uptake (VO2) and heart rate (HR) were
      measured while rebounding alone, and also while pumping 0.45 kg, 0.91 kg, and
      1.36 kg HHW to heights of 61 and 91 cm. RESULTS: All combinations of weights and
      pumping levels resulted in significantly (P < .05) higher VO2 and HR than
      rebounding alone. The estimated mean increase in VO2 was 3.2 mL/kg/min when the
      weight was increased from 0.91 kg to 1.36 kg at the 91 cm pumping height. The
      corresponding HR increase was 10.1 bpm. Similarly, when 1.36 kg weights were
      pumped at 91 cm instead of 61 cm, the mean increase in VO2 and HR was 6.2
      mL/kg/min and 11.4 bpm, respectively. CONCLUSIONS: The addition of HHW exercise
      to rebounding substantially increases exercise intensity. Because rebounding
      without weights results in a relatively low intensity, the addition of HHW should
      be considered in the use of rebounding for cardiovascular training.

PMID- 8529086
TI  - A controlled trial of a behavioral and educational intervention following
      coronary artery bypass surgery.
AB  - PURPOSE: Patients who have undergone coronary artery bypass graft surgery (CABG)
      are obvious candidates for rehabilitation programs because of the potential for
      progression of disease. Such programs have been shown to foster risk-factor
      modification, improve quality of life, and prolong survival among post-myocardial
      infarction (MI) patients. However, the efficacy of these programs has not been
      established among patients who have undergone CABG. METHODS: A randomized
      controlled trial was employed to evaluate whether a behavioral and educational
      cardiac rehabilitation program was effective in modifying cardiovascular disease
      risk factors and improving quality of life in a cohort of 86 patients after CABG.
      Patients were recruited from the cardiac ward of a large teaching hospital and
      were block-randomized to either an intervention group or routine care. Subjects
      in the intervention group attended 6 weekly group sessions following hospital
      discharge, and booster sessions at 8 months and 1 year. They also received a
      personalized behavior modification program based on their baseline risk factors.
      Risk factor and quality of life measures were recorded at baseline (6 weeks after
      surgery), 4 months, 8 months, and 1 year. RESULTS: The results indicated few
      differences between the study groups. However, the intervention group's aerobic
      capacity (VO2max) improved over that of the routine care group. With regard to
      the quality of life variables, all patients tended to improve steadily over time.
      CONCLUSIONS: The relatively moderate success of this intervention program
      compared with various post-MI studies may be indicative of differences between
      the treatment needs of patients after acute myocardial infarction or CABG. Future
      post-CABG rehabilitation research should explore these patients' unique treatment
      needs, and investigate a variety of program strategies.

PMID- 8529087
TI  - Five years of physical exercise and low fat diet: effects on progression of
      coronary artery disease.
AB  - PURPOSE: This study was designed to assess the long-term effects of low-fat diet
      and intensive physical exercise. METHODS: Long-term efficacy of exercise and diet
      was assessed in 18 nonselected, fully employed patients with symptomatic coronary
      artery disease. Results were compared to 18 patients on usual care. RESULTS: In
      the intervention group at 1 year, serum lipoproteins were brought to ideal
      levels, exercise-induced myocardial ischemia was significantly reduced, and
      progression in coronary atherosclerosis was retarded. After more than 5 years,
      patients in the intervention group showed a significant reduction in lipoprotein
      levels (total cholesterol, 248 [179-299] vs 214 [173-272] mg/dL, P < .01; low
      density lipoprotein, 146 [83-216], vs 152 [121-197] mg/dL, P < .005 vs control;
      triglycerides; 151 [80-303] mg/dl, vs 98 [46-182] mg/dL; P < .005) and body mass
      index (26 +/- 2.9 vs 25.4 +/- 3.3 kg/m2; P < .05). Exercise induced myocardial
      ischemia, measured by 201thallium scintigraphy, decreased by 29% (41 degrees +/-
      36 degrees vs 29 degrees +/- 29 degrees, P = NS) and coronary atherosclerosis,
      assessed by angiography and digital image processing, progressed at a slower pace
      in light of a 21% increase in physical work capacity (169 +/- 40 vs 205 +/- 50, P
      < .01) and a 28% increase in maximal rate pressure product (25 +/- 6 vs 32 +/- 4,
      P < .004). In contrast, patients in the control group showed only poorly
      controlled coronary risk factors (total cholesterol, 243 [179-306] vs 26 [178
      304] mg/dL, P = NS; low density lipoprotein, 151 [79-229] vs 196 [107-238] mg/dL,
      P < .0005 vs intervention; body mass index 25.7 +/- 2.5 vs 27.5 +/- 3.5 kg/m2, P
      < .01), whereas their physical work capacity tended to deteriorate (165 +/- 45 vs
      142 +/- 62 Watts, P = not significant). CONCLUSIONS: These data demonstrate that
      current usual care is insufficient in controlling risk factors of coronary artery
      disease. However, intensive physical exercise and low-fat diet remain an
      effective form of treatment after more than 5 years.

PMID- 8529089
TI  - Universal access and insurance coverage: missing pieces.

PMID- 8529088
TI  - Health promotion in minority adolescents: a Healthy People 2000 pilot study.
AB  - PURPOSE: The purpose was to evaluate the effects of a health promotion curriculum
      on health knowledge, behavior, cardiovascular fitness, and cardiovascular risk
      factors. METHODS: A multi-ethnic, multi-cultural sample (n = 54) of 10th grade
      males and females participated in a study of cardiovascular health promotion and
      coronary risk factor reduction. The sample was comprised of Asian-Americans
      (39%), blacks (33%), Hispanics (11%), whites (2%), and others (15%). Intervention
      consisted of a 10-week health promotion curriculum of classroom education modules
      in physical activity, nutrition, smoking cessation, stress management and
      personal problem solving, and an exercise program of walking and running. A
      nonintervention control group served as a basis for comparison. Classroom and
      exercise sessions met on alternate days. RESULTS: Following intervention, a
      significant treatment effect (P = .007) was observed in lowered total
      cholesterol, and significant within group improvements (P < .01) were observed in
      diet habits, percent body fat, and cardiovascular health knowledge. Comparisons
      of knowledge and social effects revealed higher cardiovascular health knowledge
      (P < .05) in subjects of nonsmoking compared to smoking parents, higher self
      perception of health (P < .01) in more active vs less active subjects and better
      dietary habits (P < .07) in children whose parents were college educated compared
      to parents who did not attend college. CONCLUSIONS: Preliminary findings suggest
      that a health promotion curriculum consisting of health education, behavior
      modification, and regular aerobic exercise lowers cholesterol, improves health
      behavior and increases health knowledge.

PMID- 8529090
TI  - Angiogenesis inhibitors generated by tumors.

PMID- 8529091
TI  - The latest fashions in skin disease.
AB  - The complex nature of epidermal tissue homeostasis is borne out by the range of
      diseases affecting this tissue. Indeed, mutations in proteins involved in
      intracellular integrity and cell-cell or cell-matrix adhesion can cause disease
      in an appropriate epidermal compartment. The most important realization in
      epidermal disease in the last two years has been that point mutations in key
      structural genes can result in filaments collapsing, cell cytolysis, or cell
      adhesion defects; and that these defects can result in severe human skin disease.
      Now that these associations have been made, the important next step will be to
      alleviate the suffering of these patients. Animal models will be an important
      part of these investigations; many molecules including growth factors, oncogenes,
      and cell adhesion molecules have been targeted to the epidermis of transgenic
      mice to investigate their role in disease. Such animal models should also
      elucidate the causes of diseases like psoriasis, a very common skin disease, the
      molecular basis of which remains elusive. Gene therapy involving the replacement
      of defective genes or local delivery of therapeutic molecules will be one of the
      main goals in alleviating these known epidermal diseases. Such protocols in the
      epidermis are aided by the relative accessibility of the skin and the presence of
      the "stem cells" in relatively accessible compartments. Indeed, as the last few
      years have shed much light on the genetic causes of epidermal disease, it is
      hoped that the next several years will prove as illuminating in the alleviation
      of these diseases.

PMID- 8529092
TI  - Odorant receptors and desensitization proteins colocalize in mammalian sperm.
AB  - BACKGROUND: The identification of transcripts encoding putative olfactory
      receptors in mammalian germ cells (1) has generated the hypothesis that olfactory
      receptors may serve a chemosensory role in sperm chemotaxis during fertilization.
      We have sought to identify and localize these receptors and their regulatory
      machinery in rat sperm in order to gain further insight into mammalian sperm
      chemotaxis and odorant receptor physiology. MATERIALS AND METHODS: We conducted
      reverse transcription-polymerase chain reaction (RT-PCR) using degenerate primers
      directed against sequences conserved across members of the known odorant receptor
      family to identify transcripts from testis and round spermatids. Western analysis
      and immunohistochemistry were performed using antibodies raised against two
      peptide sequences conserved among odorant receptors and using fusion protein
      antibodies to G-protein receptor kinase 3 (GRK3/beta ARK2) and beta-arrestin2.
      RESULTS: We detected transcripts encoding putative odorant receptors in both
      testis and round spermatids of the adult rat. Restriction digests of the PCR
      products demonstrated the existence of multiple gene products. Two anti-odorant
      receptor antibodies specifically recognized a 64 kD band in rat sperm
      preparations by Western blot. The proteins GRK3 and beta-arrestin2, implicated in
      olfactory desensitization, were detected in sperm cytosolic extracts using
      Western analysis. Immunohistochemistry colocalized putative odorant receptors,
      GRK3 and beta-arrestin2 to elongating spermatids in the testis and to the
      midpiece of mature sperm. CONCLUSIONS: The specific localization of odorant
      receptors to the respiratory center of mature sperm is consistent with a role for
      these proteins in transducing chemotactic signals. Based on the colocalization,
      it is plausible that GRK3 and beta-arrestin2 function in sperm to regulate
      putative chemoreceptor responses.

PMID- 8529093
TI  - Regulation of transcription functions of the p53 tumor suppressor by the mdm-2
      oncogene.
AB  - BACKGROUND: Mdm-2, a zinc finger protein, negatively regulates the p53 tumor
      suppressor gene product by binding to it and preventing transcriptional
      activation (16). MATERIALS AND METHODS: Assays for p53 mediated transcription,
      repression and activation by mutant and wild-type p53 proteins were used to
      measure the ability of mdm-2 to block each activity. RESULTS: Mdm-2 was able to
      inhibit all three functions of the wild-type and mutant p53 activities;
      transcriptional activation by the wild-type protein, transcriptional activation
      by the mutant p53 protein, and repression by the wild-type protein. CONCLUSIONS:
      The mdm protein binds to the amino terminal portion of the p53 protein and, in so
      doing, blocks the ability of p53 to interact with the transcriptional machinery
      of the cell (23). The mdm-2 protein binds to both leucine-tryptophan residues at
      amino acids 22 and 23, from the amino terminal end of the protein, and in so
      doing, prevents all p53 functions. The ability of a mutant p53 protein to
      transactivate a multidrug resistance-1 gene promoter is blocked by mdm-2 and the
      ability of the wild-type p53 protein to repress transcription of some genes is
      also blocked by the mdm-2 protein. Thus, all three functions of the p53 protein
      transcriptional activation, repression and mutant protein activation-require the
      p53 amino terminal domain functions and are regulated by the mdm-2 protein in a
      cell. When mdm-2 is overproduced, resulting in a tumor or transformation of a
      cell, all of the p53 activities are inactivated.

PMID- 8529094
TI  - Differential expression of human tissue factor in normal mammary epithelial cells
      and in carcinomas.
AB  - BACKGROUND: Tissue factor (TF) is a glycoprotein which binds factor VIIa. The TF
      VIIa complex serves as a potent initiator of the coagulation pathways. TF, an
      immediate early gene, may also play a role in cell growth. Expression of TF was
      correlated with some types of cancers. MATERIALS AND METHODS: Normal,
      immortalized, and tumor human mammary epithelial cells were used in the
      experiments. The differential display (DD) technique was used to identify genes
      differentially expressed in the cells. TF expression patterns were examined by
      Northern blot analysis, immunofluorescence staining of cultured cells, and
      immunohistochemical staining in human cryostat sections. RESULTS: In a 5-way
      display, an amplified polymerase chain reaction (PCR) product was found in normal
      and immortalized human mammary epithelial cells but not in the breast cancer
      cells. The PCR fragment was cloned and sequenced. The result showed that the
      fragment was identical to human tissue factor. Northern blot analysis showed that
      expression level of tissue factor mRNA remained high in growing, quiescent, and
      senescent normal mammary epithelial cells. Immunofluorescence staining also
      confirmed tissue factor expression pattern in the cell lines tested.
      Immunohistochemical staining showed that tissue factor was expressed in the
      normal luminal and myoepithelial cells of some ducts but not others. No staining
      was observed in invasive carcinoma cells. However, myoepithelial cell staining
      was seen in some residual ductal structures in invasive tumors. CONCLUSIONS: This
      study shows the use of DD to reveal the loss of TF expression pattern in human
      breast cancer cell lines. Immunohistochemical staining results showed breast
      carcinoma cells expressed little TF, if any, suggesting that TF is not required
      for breast tumor cell invasion. The results also indicated that TF expression was
      independent of the proliferation status of the expressing cells. The expression
      pattern of TF may be a meaningful marker in the development of breast cancer.

PMID- 8529095
TI  - Association between HLA DQB1 * 03 and cervical intra-epithelial neoplasia.
AB  - BACKGROUND: Cervical intraepithelial neoplasia (CIN) and cervical cancer have
      been shown to be strongly associated with infection by human papillomavirus
      (HPV). However, other factors may be contributory in the progression from normal
      epithelium to CIN and cervical cancer, since not all women with HPV infection
      develop disease. Recently, it was demonstrated that there is a high risk for
      cervical cancer and CIN in women with HLA DQB1 * 03 (RR = 7.1, p < 0.0009) (1).
      Subsequent reports have been conflicting, due to sample size, genetic
      heterogeneity and differences in the techniques employed for the detection of HLA
      DQB1 * 03. MATERIALS AND METHODS: DNA from cervical smears of 178 women with CIN
      and 420 controls with normal cervical cytology was analyzed by polymerase chain
      reaction (PCR) with type-specific primers for HPV 16, 18, 31, and 33. The DNA
      from test and control samples were also analyzed by a novel PCR technique, which
      mutates the first base of codon 40 (DQ alleles) from T to G to create an
      artificial restriction site for an enzyme Mlu I that distinguish DQB1 * 03 from
      other alleles and are confirmed by digestion of amplified DNA with Mlu I. Further
      analysis of individual DQB1 * 03 alleles was performed using PCR and allele
      specific primers. RESULTS: One hundred forty-four (34%) out of 420 controls (all
      HPV 16, 18, 31, or 33 negative and normal cytology), 37/66 (56%) of CIN I and
      72/112 (64%) of CIN III were positive for DQB1 * 03 (trend test, p < 0.001, chi 2
      = 37.3). A significant association was observed between DQB1 * 03 and CIN (odds
      ratio 3.03; 95% CI 2.11-3.45). Of women with CIN, 131/178 (73.5%) had HPV (types
      16, 18, 31, or 33) infection. There was a significant association between DQB1 *
      03 and presence of HPV (odds ratio 3.43; 95% CI 2.25-5.10). Homozygosity for DQB1
      * 03 was more strongly associated with CIN than heterozygosity (odds ratios 4.0
      and 2.63, respectively); and for the presence of HPV (odds ratio 4.47; 95% CI
      2.58-7.77). HLA DQB1 * 0301 was the most strongly associated allele with CIN and
      HPV (odds ratios 2.53 and 2.63, respectively). CONCLUSIONS: HLA DQB1 * 03 is
      associated significantly with CIN and may be permissive for HPV infection.
      Further analysis of class II HLA typing in CIN is necessary to evaluate this
      association.

PMID- 8529096
TI  - Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene
      inhibits vascular smooth muscle cell proliferation and neointima formation
      following balloon angioplasty of the rat carotid artery.
AB  - BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation following arterial
      injury plays a critical role in a variety of vascular proliferative disorders,
      including atherosclerosis and restenosis after balloon angioplasty. In this
      study, we tested the hypothesis that localized arterial infection at the time of
      balloon angioplasty with an adenovirus (ADV-tk) encoding the herpes simplex virus
      thymidine kinase gene (HSV-tk), followed by systemic ganciclovir administration,
      can inhibit VSMC proliferation and neointima formation in a well-characterized
      model of arterial injury and restenosis. MATERIALS AND METHODS: The left carotid
      arteries of 31 male Sprague-Dawley rats were subjected to balloon angioplasty and
      immediately infected with 2 x 10(9) pfu of either ADV-tk or a control adenovirus
      that does not encode a recombinant protein (ADV-delta E1). Twenty-four hours
      after injury, animals from each experimental group were randomized to receive a
      course of systemic ganciclovir (ADV-tk/+GC, ADV delta E1/+GC) or saline (ADV-tk/
      GC, ADV-delta E1/-GC). VSMC DNA synthesis was measured by 5'-bromodeoxuridine
      (BrdU) incorporation 2-4 days after balloon injury. The extent of restenosis,
      expressed as the neointima to media (I/M) area ratio was determined by digital
      planimetry 20 days after balloon injury in each of the four treatment groups.
      Immunohistochemistry using a mAb to von Willebrand factor (vWF) was used to
      determine the effects of ADV-tk infection and ganciclovir treatment on re
      endothelialization of the carotid arteries 20 days following balloon angioplasty.
      RESULTS: Forty-one percent of the medial VSMCs in the ADV-tk/-GC arteries were
      labeled with BrdU 4 days after balloon injury. In contrast, ADV-tk infected
      animals that were treated with systemic ganciclovir (ADV-tk/+GC) displayed a 40%
      reduction in BrdU-staining medial VSMCs (p < 0.03). I/M area ratios of the three
      control groups were 1.17 +/- 0.18 (ADV-tk/-GC, n = 5), 1.15 +/- 0.10 (ADV-delta
      E1/+GC, n = 6), and 0.91 +/- 0.08 (ADV-delta E1/-GC, n = 6). These differences
      were not statistically significant (p > 0.05). In contrast, the ADV-tk/+GC
      animals (n = 6) displayed an I/M area ratio of 0.49 +/- 0.13 which was
      significantly lower than that seen in each of the three control groups (p <
      0.02). None of the treated animals showed evidence of significant organ toxicity
      at autopsy. A regenerated endothelium was observed in the ADV-tk/+GC animals 20
      days after balloon injury. CONCLUSIONS: Localized arterial infection with ADV-tk
      at the time of balloon angioplasty followed by systemic ganciclovir therapy
      reduces VSMC proliferation and neointimal expansion in the rat carotid artery
      injury model. Moreover, combined treatment with ADV-tk and systemic ganciclovir
      does not result in systemic toxicity and appears to selectively eliminate
      proliferating VSMCs, while preserving the capacity of the injured arterial
      segments to re-endothelialize within 3 weeks of injury. Taken together, these
      results support the feasibility of using this gene therapy approach for the
      treatment of human vascular proliferative disorders.

PMID- 8529097
TI  - Hypoxic induction of endothelial cell growth factors in retinal cells:
      identification and characterization of vascular endothelial growth factor (VEGF)
      as the mitogen.
AB  - BACKGROUND: New vessel growth is often associated with ischemia, and hypoxic
      tissue has been identified as a potential source of angiogenic factors. In
      particular, ischemia is associated with the development of neovascularization in
      a number of ocular pathologies. For this reason, we have studied the induction of
      endothelial cell mitogens by hypoxia in retinal cells. MATERIALS AND METHODS:
      Human retinal pigment epithelium (hRPE) were grown under normoxic and hypoxic
      conditions and examined for the production of endothelial mitogens. Northern
      analysis, biosynthetic labeling and immunoprecipitation, and ELISA were used to
      assess the levels of vascular endothelial growth factor/vascular permeability
      factor (VEGF) and basic fibroblast growth factor (bFGF), two endothelial cell
      mitogens and potent angiogenic factors. Soluble receptors for VEGF were employed
      as competitive inhibitors to determine the contribution of the growth factor to
      the hypoxia-stimulated mitogen production. RESULTS: Following 6-24 hr of hypoxia,
      confluent and growing cultures of hRPE increase their levels of VEGF mRNA and
      protein synthesis. Biosynthetic labeling studies and RT-PCR analysis indicate
      that the cells secrete VEGF121 and VEGF165, the soluble forms of the angiogenic
      factor. In contrast, hRPE cultured under hypoxic conditions show reduced steady
      state levels of basic fibroblast growth factor (bFGF) mRNA and decreased bFGF
      protein synthesis. Unlike VEGF, bFGF is not found in conditioned media of hRPE
      following 24 hr of hypoxia. Using a soluble high-affinity VEGF receptor as a
      competitive inhibitor of VEGF, we demonstrate that a VEGF-like activity is the
      sole hypoxia-inducible endothelial mitogen produced by cultured hRPE.
      CONCLUSIONS: From this comparison we conclude that hRPE do not respond to hypoxia
      with a general, nonspecific increase in the overall levels of growth factors, as
      is seen during cell wounding responses or serum stimulation. The physiological
      relevance of data from this in vitro model are affirmed by separate studies in an
      animal model of retinal ischemia-induced ocular neovascularization (1) in which
      retina-derived VEGF levels have been shown to correlate spatio-temporally with
      the onset of angiogenesis. Taken together, these data support the hypothesis that
      the induction of VEGF by hypoxia mediates the rapid, initial angiogenic response
      to retinal ischemia.

PMID- 8529098
TI  - Genomic organization and sequence of the human NRAMP gene: identification and
      mapping of a promoter region polymorphism.
AB  - BACKGROUND: Murine Nramp is a candidate for the macrophage resistance gene
      Ity/Lsh/Bcg. Sequence analysis of human NRAMP was undertaken to determine its
      role in man. MATERIALS AND METHODS: A yeast artificial chromosome carrying NRAMP
      was subcloned and positive clones sequenced. The transcriptional start site was
      mapped using 5' RACE PCR. Polymorphic variants were amplified by PCR. Linkage
      analysis was used to map NRAMP. RESULTS: NRAMP spans 12kb and has 15 exons
      encoding a 550 amino acid protein showing 85% identity (92% similarity) with
      Nramp. Two conserved PKC sites occur in exon 2 encoding the Pro/Ser rich SH3
      binding domain, and in exon 3. Striking sequence similarities (57 and 53%) were
      observed with yeast mitochondrial proteins, SMF1 and SMF2, especially within
      putative functional domains: exon 6 encoding the second transmembrane spanning
      domain, site of the murine susceptibility mutation; and exon 11 encoding a
      conserved transport motif. No mutations comparable to the murine susceptibility
      mutation were found. The transcriptional initiation site mapped 148 bp 5' of the
      translational initiation codon. 440bp of 5' flanking sequence contained putative
      promoter region elements: 6 interferon-gamma response elements, 3 W-elements, 3
      NF kappa B binding sites and 1 AP-1 site. Nine purine-rich GGAA core motifs for
      the myeloid-specific PU.1 transcription factor were identified, two combining
      with imperfect AP1-like sites to create PEA3 motifs. TATA, GC and CCAAT boxes
      were absent. A possible enhancer element containing the Z-DNA forming
      dinucleotide repeat t(gt),ac(gt),ac(gt),g was polymorphic (4 alleles; n =
      4,9,10,11), and was used to map NRAMP to 2q35. CONCLUSIONS: This analysis
      provides important resources to study the role of NRAMP in human disease.

PMID- 8529101
TI  - Molecular medicine database.

PMID- 8529099
TI  - Expression cloning of cDNAs that render cancer cells resistant to Pseudomonas and
      diphtheria toxin and immunotoxins.
AB  - BACKGROUND: Several immunotoxins in which antibodies are coupled to plant or
      bacterial toxins are now in clinical trials for the treatment of cancer. One of
      these is B3-LysPE38 in which MAb B3 which reacts with many human cancers, is
      coupled with a genetically modified form of Pseudomonas exotoxin (PE). MATERIALS
      AND METHODS: To investigate how cells can become resistant to PE-derived
      immunotoxins, we constructed an immunotoxin-sensitive MCF-7 breast cancer cell
      line that contains SV40 T antigen and allows episomal replication of SV40 origin
      containing plasmids. We transfected a pCDM8/HeLa cDNA expression library into
      these cells, thereby causing over-expression of the plasmid-encoded genes. The
      transfected cells were treated with immunotoxin to select for resistance
      mediating plasmids, which were reisolated from these cells and amplified in
      Escherichia coli. The resulting plasmid pool was transfected into cells for two
      further rounds of selection and plasmid reisolation. RESULTS: Several plasmids
      that caused immunotoxin resistance were enriched by this selection procedure.
      Four plasmids were stably transfected into MCF-7 cells and found to increase
      their resistance to PE-derived immunotoxins by 5- to 20-fold. These plasmids also
      confer resistance to native PE and to diphtheria toxin but not to ricin or
      cycloheximide. Thus, they appear to specifically interfere with the action of ADP
      ribosylating toxins. CONCLUSION: Cancer cells can become resistant to
      immunotoxins by deregulated expression of normal genes. The clinical significance
      of this type of resistance will be evaluated in clinical trials.

PMID- 8529100
TI  - Nuclear localization signal of HIV-1 as a novel target for therapeutic
      intervention.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is a lentivirus and
      shares with other members of this retroviral subfamily the ability to replicate
      in nondividing cells, in particular, cells of the monocyte/macrophage lineage.
      This feature relies on the presence of a specific nuclear localization signal
      (NLS) within the viral matrix protein (MA p17), which to some degree can be
      complemented by the activity of the viral vpr gene product. The MA p17 NLS
      ensures efficient transportation of the viral preintegration complex into the
      nucleus of an infected macrophage and confers persistence of HIV-1 in quiescent T
      cells, and therefore presents an attractive target for therapeutic intervention.
      MATERIALS AND METHODS: Nuclear localization signals (NLS) in general and the HIV
      1 MA p17 NLS in particular are characterized by a stretch of positively charged
      amino acids including one or more lysine residues. A series of compounds
      potentially capable of binding and reacting with lysine by forming Schiff base
      adducts was synthesized. Our special consideration was to make compounds that
      would preferentially bind to two closely contiguous amino functions, as opposed
      to isolated single lysine residues. We assumed that this approach might
      specifically target the compound to NLS while affecting other regions less, thus
      reducing nonspecific cytotoxicity. Antiviral activity was assessed in primary
      monocytes and in peripheral blood lymphocytes (PBL) infected with HIV-1ADA
      strain. Viral replication was monitored by reverse transcriptase (RT) activity in
      the supernatant. Efficiency of nuclear importation of the viral preintegration
      complex was estimated by the formation of 2-LTR circle forms of HIV-1 DNA and
      also by in situ PCR techniques. RESULTS: Arylene bis(methyl ketone) compounds
      with a nitrogenous third subsituent, especially a pyrimidinic side-chain,
      inhibited HIV-1 replication in human monocytes at an IC50 as low as 1 nM. These
      compounds did not block HIV-1 replication in peripheral blood lymphocyte
      cultures. The inhibitory effect observed in monocyte cultures appeared in the
      context of markedly reduced nuclear importation of viral DNA in the presence of
      the drug. No cytotoxic effects of the compounds was observed in vitro at
      concentrations as high as 10 microM. An amidinohydrazone derivative of the most
      active compound was about 100 times less active than the parent, indicating that
      carbonyl groups were instrumental in the antiviral effect. CONCLUSIONS: These
      early results suggest that retroviral replication in nondividing cells is
      susceptible to pharmaceutical intervention targeted against the NLS activity of
      HIV-1 proteins in the viral preintegration complex. The compounds described
      efficiently block translocation of viral DNA to the nuclei of infected primary
      monocytes, and inhibit viral replication. This inhibition is effective only in
      nondividing cells and is not seen in proliferating cultures, such as activated
      PBLs. Thus, drugs that target HIV-1 NLS may be useful to specifically block the
      macrophage arm of HIV infection and could thereby be of value in treating
      macrophage-specific manifestations of HIV disease, such as HIV-1 dementia. In
      combination with other drugs, potential therapeutics exploiting this target may
      also help to control the progression of HIV-1 infection and disease.

PMID- 8529102
TI  - A molecular medicine database.

PMID- 8529103
TI  - Autoantibodies to neuronal glutamate receptors in patients with paraneoplastic
      neurodegenerative syndrome enhance receptor activation.
AB  - BACKGROUND: Paraneoplastic syndromes are "remote" complications of cancer
      characterized clinically by neurological disease. The sera and cerebrospinal
      fluid (CSF) from patients with paraneoplastic neurological syndromes (PNS)
      frequently contain autoantibodies to ill-defined neuronal antigens. We report
      here that neuronal glutamate receptors are targets for autoantibodies found in
      the serum from some patients with well-characterized PNS. MATERIALS AND METHODS:
      We have analyzed the serum from seven patients with well-characterized PNS for
      the presence of autoreactive antibodies to non-NMDA glutamate receptor subunits.
      Autoantibodies were assessed using Western blot, immunohistochemistry, and
      immunocytochemistry. Whole-cell electrophysiological recordings were used to
      examine the effect of antibodies on glutamate receptors expressed by cortical
      neurons in culture. RESULTS: Six of seven patients' serum contained
      autoantibodies to the non-NMDA glutamate receptor (GluR) subunits GluR1, GluR4,
      and/or GluR5/6. No patient had autoantibodies to GluR2, and only one patient
      exhibited weak immunoreactivity to GluR3. Electrophysiological analysis
      demonstrated that the serum from four of the six GluR-antibody-positive patients
      enhanced glutamate-elicited currents on cultured cortical neurons but had no
      effect on receptor function alone. Enhancement of glutamate-elicited currents was
      also produced by affinity-purified antibody to GluR5. CONCLUSIONS: The occurrence
      of autoantibodies to specific neuronal neurotransmitter subunits in the sera of
      patients with PNS and the ability of these autoantibodies to modulate
      glutaminergic receptor function suggest that some paraneoplastic neurological
      injury could result from glutamate-mediated excitotoxicity.

PMID- 8529104
TI  - An inhibitor of macrophage arginine transport and nitric oxide production (CNI
      1493) prevents acute inflammation and endotoxin lethality.
AB  - BACKGROUND: Nitric oxide (NO), a small effector molecule produced enzymatically
      from L-arginine by nitric oxide synthase (NOS), is a mediator not only of
      important homeostatic mechanisms (e.g., blood vessel tone and tissue perfusion),
      but also of key aspects of local and systemic inflammatory responses. Previous
      efforts to develop inhibitors of NOS to protect against NO-mediated tissue damage
      in endotoxin shock have been unsuccessful, largely because such competitive NOS
      antagonists interfere with critical vasoregulatory NO production in blood vessels
      and decrease survival in endotoxemic animals. Accordingly, we sought to develop a
      pharmaceutical approach to selectively inhibit NO production in macrophages while
      sparing NO responses in blood vessels. MATERIALS AND METHODS: The process of
      cytokine-inducible L-arginine transport and NO production were studied in the
      murine macrophage-like cell line (RAW 264.7). A series of multivalent
      guanylhydrazones were synthesized to inhibit cytokine-inducible L-arginine
      transport. One such compound (CNI-1493) was studied further in animal models of
      endothelial-derived relaxing factor (EDRF) activity, carrageenan inflammation,
      and lethal lipopolysaccharide (LPS) challenge. RESULTS: Upon activation with
      cytokines, macrophages increase transport of L-arginine to support the production
      of NO by NOS. Since endothelial cells do not require this additional arginine
      transport to produce NO, we reasoned that a competitive inhibitor of cytokine
      inducible L-arginine transport would not inhibit EDRF activity in blood vessels,
      and thus might be effectively employed against endotoxic shock. CNI-1493, a
      tetravalent guanylhydrazone, proved to be a selective inhibitor of cytokine
      inducible arginine transport and NO production, but did not inhibit EDRF
      activity. In mice, CNI-1493 prevented the development of carrageenan-induced
      footpad inflammation, and conferred protection against lethal LPS challenge.
      CONCLUSIONS: A selective inhibitor of cytokine-inducible L-arginine transport
      that does not inhibit vascular EDRF responses is effective against endotoxin
      lethality and significantly reduces inflammatory responses.

PMID- 8529105
TI  - Nramp transfection transfers Ity/Lsh/Bcg-related pleiotropic effects on
      macrophage activation: influence on oxidative burst and nitric oxide pathways.
AB  - BACKGROUND: The Ity/Lsh/Bcg gene on mouse chromosome 1 regulates
      priming/activation of macrophages for antimicrobial and tumouricidal activity. A
      candidate gene expressed in macrophages has been identified by positional cloning
      and full-length sequence analysis, and encodes the Natural resistance-associated
      macrophage protein (Nramp). In this study, we have tested the hypothesis that the
      Nramp gene corresponds to Ity/Lsh/Bcg. MATERIALS AND METHODS: In vitro
      transfection was used to introduce the resistant allele into the macrophage cell
      line RAW 264.7 derived from the recessive susceptible BALB/c mouse strain.
      Expression of the transgene was monitored on the background of the endogenous
      susceptible allele by allele-specific oligonucleotide hybridization. RESULTS:
      Expression of the transgene correlated with three Lshr-associated
      lipopolysaccharide/interferon-gamma-regulated macrophage activation phenotypes:
      respiratory burst, nitrite release, and uptake of L-arginine. Endogenous and
      stimulated L-arginine fluxes were inhibitable with the radical scavengers
      nordihydroguaiaretic acid and butylated hydroxyanisole. The mitochondrial
      electron transport inhibitors, rotenone and thenoyltrifluoroacetone, inhibited
      respiratory burst, and rotenone suppressed L-arginine flux, implying that
      mitochondrial-derived oxygen radicals are important mediators in Nramp-regulated
      signal transduction pathways. CONCLUSIONS: These data provide the first direct
      evidence that Nramp is the product of the Ity/Lsh/Bcg gene, and are consistent
      with the hypothesis that the many pleiotropic effects of this gene on macrophage
      activation may all derive from the requirement for mitochondrial generation of
      oxygen radicals for intracellular signaling.

PMID- 8529106
TI  - Construction of a novel bifunctional biogenic amine receptor by two point
      mutations of the H2-histamine receptor.
AB  - BACKGROUND: H2-histamine receptors mediate a wide range of physiological
      functions extending from stimulation of gastric acid secretion to induction of
      human promyelocyte differentiation. We have previously cloned the H2-histamine
      receptor gene and noted that only three amino acids on the receptor were
      sufficient to define its specificity and selectivity. Despite only modest overall
      amino acid homology (34% amino acid identity and 57.5% similarity) between the H2
      histamine receptor and the receptor for another monoamine, the beta 2-adrenergic
      receptor, there is remarkable similarity at their critical ligand binding sites.
      We hypothesized that, if the specificity and selectivity of both receptors are
      invested in just three amino acids, it should be possible to convert one of the
      receptors into one that recognizes the ligand of the other by simple mutations at
      only one or two sites. MATERIAL AND METHODS: We explored the effect of two single
      mutations in the fifth transmembrane domain of the H2-histamine receptor, which
      encompasses the sites that determine H2 selectivity. The canine H2 receptor gene
      was mutated at Asp186 and Gly187 (Asp186 to Ala186 and Gly187 to Ser187) by
      oligonuceotide directed mutagenesis. The coding region of both the wild-type and
      mutated H2 receptors was subcloned into the eukaryotic expression vector, CMVneo,
      and stably transfected into Hepa cells and L cells. The biological activity of
      histamine and epinephrine on the expressed receptor was examined by measurement
      of cellular cAMP production and inositol trisphosphate formation. RESULTS: Hepa
      cells transfected with the Ala186-Ser187 mutant H2 receptor demonstrated a
      biphasic rise in cAMP in response to epinephrine with an early phase (ED50
      approximately 10(-11) M) that could be inhibited by both propranolol and
      cimetidine. Epinephrine also induced IP3 generation in the same cells, a
      biological response that is characteristic of activation of the wild-type H2 but
      not of the beta-adrenergic receptor. L cells transfected with the Ala186-Ser187
      mutant H2 receptor also responded to epinephrine in a cimetidine and propranolol
      inhibitable manner. CONCLUSIONS: We converted the H2-histamine receptor into a
      bifunctional one that has characteristics of both histamine and adrenergic
      receptors by two simple mutations. These results support the hypothesis that
      ligand specificity is determined by only a few key points on a receptor
      regardless of the structure of the remainder of the molecule. Our studies have
      important implications on the design of pharmacological agents targeted for
      action at physiological receptors.

PMID- 8529107
TI  - Restricted usage of T cell receptor V alpha/J alpha gene segments with different
      nucleotide but identical amino acid sequences in HLA-DR3+ sarcoidosis patients.
AB  - BACKGROUND: Sarcoidosis is a granulomatous disease characterized by the
      accumulation of activated T cells in the lungs. We previously showed that
      sarcoidosis patients expressing the HLA haplotype DR3(17),DQ2 had increased
      numbers of lung CD4+ T cells using the T cell receptor (TCR) variable region (V)
      alpha 2.3 gene segment product. In the present study, the composition of both the
      TCR alpha- and beta-chains of the expanded CD4+ lung T cells from four
      DR3(17),DQ2+ sarcoidosis patients was examined. MATERIALS AND METHODS: TCR alpha
      chains were analyzed by cDNA cloning and nucleotide sequencing. TCR beta-chains
      were analyzed for V beta usage by flow cytometry using TCR V-specific monoclonal
      antibodies or by the polymerase chain reaction (PCR) using V beta- and C beta
      specific primers. J beta usage was analyzed by Southern blotting of PCR products
      and subsequent hybridization with radiolabeled J beta-specific probes. RESULTS:
      Evidence of biased J alpha gene segment usage by the alpha-chains of V alpha 2.3+
      CD4+ lung T cells was found in four out of four patients. Both different alpha
      chain nucleotide sequences coding for identical amino acid sequences and a number
      of identically repeated alpha-chain sequences were identified. In contrast, the
      TCR beta-chains of FACS-sorted V alpha 2.3+ CD4+ lung T cells were found, with
      one exception, to have a nonrestricted TCR V beta usage. CONCLUSIONS: The finding
      of V alpha 2.3+ CD4+ lung T cells with identical TCR alpha-chain amino acid
      sequences but with different nucleotide sequences strongly suggests that
      different T cell clones have been selected to interact with a specific
      sarcoidosis associated antigen(s). The identification of T cells with restricted
      TCR usage, which may play an important role in the development of sarcoidosis,
      and the possibility of selectively manipulating these cells should have important
      implications for the treatment of the disease.

PMID- 8529108
TI  - Hemoglobin switching in humans is accompanied by changes in the ratio of the
      transcription factors, GATA-1 and SP1.
AB  - BACKGROUND: Understanding the mechanism of developmental regulation of hemoglobin
      switching has scientific as well as clinical relevance because of the influence
      of fetal hemoglobin (HbF) production in adulthood on the clinical manifestation
      of thalassemia and sickle cell anemia. We have previously found that the normal
      developmental patterns of globin gene expression are recapitulated in an
      experimental system of primary cultures that support differentiation of erythroid
      progenitors. We further found that high activities of the transcriptional
      activators, GATA-1 and SP1, are associated with normal adult erythroid
      differentiation. MATERIALS AND METHODS: In the present work, we have studied, the
      activities of GATA-1 and SP1 during differentiation of cultured erythroid
      progenitors derived from cord blood and from fetal livers, as well as from beta
      zero-thalassemia patients. RESULTS: The results showed high GATA-1 binding
      activity and very low SP1 activity in the fetal liver cultures. This pattern was
      in contrast to cultures derived from normal adult peripheral blood, in which both
      GATA-1 and SP1 activities were high. Cord blood cultures showed an additive
      combination of "adult" and "fetal" patterns. The progenitors derived from a beta
      zero-thalassemia patient with high HbF production showed "fetal" pattern. On the
      other hand, in cultures of 2 beta zero-thalassemia patients without high HbF,
      "adult" pattern was observed. CONCLUSIONS: In the present work, we show that
      human fetal and adult erythroid progenitors are distinct in their transcription
      factors, and that the commitment to fetal or adult program occurs at a very early
      differentiation stage. Our studies also demonstrate that under anemic stress,
      recruitment of fetal progenitors may occur in adulthood.

PMID- 8529109
TI  - Cell type-dependent modulation of the dominant negative action of human mutant
      thyroid hormone beta 1 receptors.
AB  - BACKGROUND: Mutations in the ligand-binding domain of the thyroid hormone
      receptor beta (TR beta) gene cause the syndrome of resistance to thyroid hormone
      (RTH). The clinical phenotype results from the antagonism of the normal TR alpha
      and the non-mutated TR beta alleles by the TR beta 1 mutants, via a dominant
      negative effect. There is, however, marked heterogeneity of organ resistance
      within and among kindreds with RTH. This study examines the potential role of
      cell type in modulating the dominant negative potency of human TR beta 1 (h-TR
      beta 1) mutants. MATERIALS AND METHODS: Transient transfections were performed in
      HeLa and NIH3T3 cells, using a wild type (WT) and three naturally occurring
      mutant h-TR beta 1 constructs, and three natural thyroid hormone response
      elements (TREs). Immunocytochemistry was performed to detect levels of TR beta 1
      expression in these two cell types. In order to determine how TR beta 1 interacts
      with other cellular partners, gel-shift analyses using HeLa and NIH3T3 nuclear
      extracts were performed. RESULTS: Transfection studies using WT h-TR beta 1 in
      HeLa and NIH3T3 cells, showed that the 3,3',5-triiodothyronine (T3)-induced
      transactivation of the different TREs varied between cell types. Unlike the non
      T3-binding h-TR beta 1 mutant, PV, mutants ED and OK displayed the expected T3
      induced dose responsiveness in these two cell types. For each TRE examined, the
      magnitude of the dominant negative effect varied between the cell types. The
      levels of receptor expression in HeLa and NIH3T3 cells were identical, as
      determined by immunocytochemistry. Gel-shift analyses showed differences in the
      formation of hetero- and homodimers depending on both the cell type and TRE
      motif. CONCLUSIONS: The cell type in which a mutant receptor operates affects the
      relative amounts of hetero- and homodimers. Together with the nature of the
      mutation and the TRE-motif, this could modulate the dominant negative action of
      mutant receptors in different tissues, which, in turn, could contribute to the
      variable phenotypic characteristics of RTH.

PMID- 8529110
TI  - Failure of alglucerase infused into Gaucher disease patients to localize in
      marrow macrophages.
AB  - BACKGROUND: Gaucher disease is a common glycolipid storage disease, caused by a
      deficiency of lysosomal beta-glucosidase (glucocerebrosidase). Alglucerase is a
      form of glucocerebrosidase enriched with terminal mannose moieties, so as to
      "target" the preparation to the high-affinity macrophage receptor in patients
      with Gaucher disease. Our earlier in vitro studies indicated that alglucerase was
      bound by cells other than macrophages by a widely distributed, low-affinity
      mannose receptor. MATERIALS AND METHODS: Bone was removed at surgery from six
      patients with Gaucher disease; in three cases, bone was obtainable both when the
      patient was untreated and after receiving an infusion of alglucerase. Four
      samples of bone were obtained from patients without Gaucher disease and served as
      controls. A bone marrow aspirate was obtained from another patient with Gaucher
      disease immediately after enzyme infusion. Marrow beta-glucosidase activity and
      chitotriosidase (a macrophage marker) was determined on all samples. RESULTS:
      Even with the large bolus doses used for the treatment of Gaucher disease by
      some, scarcely any beta-glucosidase activity was found in marrow samples; the
      amount of the enzyme was much less than would have been anticipated had the
      enzyme been evenly distributed to all body cells. CONCLUSIONS: Alglucerase is not
      targeted to marrow macrophages. Its unquestioned therapeutic effectiveness must
      be due either to its activity at some site other than marrow macrophages or to
      the fact that the doses administered are so enormous that even a small fraction
      is sufficient to achieve a therapeutic effect.

PMID- 8529111
TI  - Immunogenicity and in vivo efficacy of recombinant Plasmodium falciparum
      merozoite surface protein-1 in Aotus monkeys.
AB  - BACKGROUND: The carboxy-terminus of the merozoite surface protein-1 (MSP1) of
      Plasmodium falciparum has been implicated as a target of protective immunity.
      MATERIALS AND METHODS: Two recombinant proteins from the carboxy-terminus of
      MSP1, the 42 kD fused to GST (bMSP1(42)) and the 19 kD (yMSP1(19)), were
      expressed in Escherichia coli and secreted from Saccharomyces cerevisiae,
      respectively. To determine if vaccination with these recombinant proteins induces
      protective immunity, we conducted a randomized, blinded vaccine trial in two
      species of Aotus monkeys, A. nancymai and A. vociferans. After three injections
      using Freund's adjuvant, the monkeys were challenged with the virulent Vietnam
      Oak Knoll (FVO) strain of P. falciparum. RESULTS: All three control monkeys
      required treatment by Day 19. Two of three monkeys vaccinated with bMSP1(42)
      required treatment by Day 17, whereas the third monkey controlled parasitemia for
      28 days before requiring treatment. In contrast, both of the A. nancymai
      vaccinated with yMSP1(19) self-resolved an otherwise lethal infection. One of the
      two yMSP1(19)-vaccinated A. vociferans had a prolonged prepatent period of > 28
      days before requiring treatment. No evidence of mutations were evident in the
      parasites recovered after the prolonged prepatent period. Sera from the two A.
      nancymai that self-cured had no detectable effect on in vitro invasion.
      CONCLUSIONS: Vaccination of A. nancymai with yMSP1(19) induced protective immune
      responses. The course of recrudescing parasitemias in protected monkeys suggested
      that immunity is not mediated by antibodies that block invasion. Our data
      indicate that vaccine trials with the highly adapted FVO strain of P. falciparum
      can be tested in A. nancymai and that MSP1(19) is a promising anti-blood-stage
      vaccine for human trials.

PMID- 8529112
TI  - Molecular medicine database.

PMID- 8529113
TI  - Yale's Boyer Center for molecular medicine.

PMID- 8529114
TI  - HIV accessory proteins: emerging therapeutic targets.

PMID- 8529115
TI  - A role for T cells in the pathogenesis of treatment-resistant Lyme arthritis.

PMID- 8529116
TI  - Burkitt's lymphoma is a malignancy of mature B cells expressing somatically
      mutated V region genes.
AB  - BACKGROUND: The developmental stage from which stems the malignant B cell
      population in Burkitt's lymphoma (BL) is unclear. An approach to answering this
      question is provided by the sequence analysis of rear-ranged immunoglobulin (Ig)
      variable region (V) genes from BL for evidence of somatic mutations, together
      with a phenotypic characterization. As somatic hypermutation of Ig V region genes
      occurs in germinal center B cells, somatically mutated Ig genes are found in
      germinal center B cells and their descendents. MATERIALS AND METHODS: Rearranged
      V kappa region genes from 10 kappa-expressing sporadic and endemic BL-derived
      cell lines (9 IgM and 1 IgG positive) and three kappa-expressing endemic BL
      biopsy specimens were amplified by polymerase chain reaction and sequenced. In
      addition, VH region gene sequences from these cell lines were determined.
      RESULTS: All BL cell lines and the three biopsy specimens carried somatically
      mutated V region genes. The average mutation frequency of rearranged V kappa
      genes from eight BL cell lines established from sporadic BL was 1.8%. A higher
      frequency (6%) was found in five endemic cases (three biopsy specimens and two BL
      cell lines). CONCLUSIONS: The detection of somatic mutations in the rearranged V
      region genes suggests that both sporadic and endemic BL represent a B-cell
      malignancy originating from germinal center B cells or their descendants.
      Interestingly, the mutation frequency detected in sporadic BL is in a range
      similar to that characteristic for IgM-expressing B cells in the human peripheral
      blood and for mu chain-expressing germinal center B cells, whereas the mutation
      frequency found in endemic BL is significantly higher.

PMID- 8529117
TI  - Taxol-induced mitotic block triggers rapid onset of a p53-independent apoptotic
      pathway.
AB  - BACKGROUND: At therapeutic concentrations, the antineoplastic agent taxol
      selectively perturbs mitotic spindle microtubules. Taxol has recently been shown
      to induce apoptosis, similar to the mechanism of cell death induced by other
      antineoplastic agents. However, taxol has shown efficacy against drug-refractory
      cancers, raising the possibility that this pharmacological agent may trigger an
      alternative apoptotic pathway. MATERIALS AND METHODS: The kinetics and IC50 of
      mitotic (M) block, aberrant mitosis, and cytotoxicity following taxol treatment
      were analyzed in human cell lines as well as normal mouse embryo fibroblasts
      (MEFs) and MEFs derived from p53-null mice. Apoptosis was followed by DNA gel
      electrophoresis and by in situ DNA end-labeling (TUNEL). RESULTS: Taxol induced
      two forms of cell cycle arrest: either directly in early M at prophase or, for
      those cells progressing through aberrant mitosis, arrest in G1 as
      multimininucleated cells. TUNEL labeling revealed that DNA nicking occurred
      within 30 min of the arrest in prophase. In contrast, G1-arrested,
      multimininucleated cells became TUNEL positive only after several days. In the
      subset of cells that became blocked directly in prophase, both wt p53-expressing
      and p53-null MEFs responded similarly to taxol, showing rapid onset of DNA
      nicking and apoptosis. However, p53-null MEFs progressing through aberrant
      mitosis failed to arrest in the subsequent G1 phase or to become TUNEL positive,
      and remained viable. CONCLUSIONS: Taxol induces two forms of cell cycle arrest,
      which in turn induce two independent apoptotic pathways. Arrest in prophase
      induces rapid onset of a p53-independent pathway, whereas G1-block and the
      resulting slow (3-5 days) apoptotic pathway are p53 dependent.

PMID- 8529118
TI  - Nerve growth factor prevents both neuroretinal programmed cell death and
      capillary pathology in experimental diabetes.
AB  - BACKGROUND: Chronic diabetes causes structural changes in the retinal capillaries
      of nearly all patients with a disease duration of more than 15 years. Acellular
      occluded vessels cause hypoxia, which stimulates sight-threatening abnormal
      angiogenesis in 50% of all type I diabetic patients. The mechanism by which
      diabetes produces acellular retinal capillaries is unknown. MATERIALS AND
      METHODS: In this study, evidence of programmed cell death (PCD) was sought in the
      retinas of early diabetic rats, and the effect of nerve growth factor (NGF) on
      PCD and capillary morphology was evaluated. RESULTS: Diabetes induced PCD
      primarily in retinal ganglion cells (RGC) and Muller cells. This was associated
      with a transdifferentiation of Muller cells into an injury-associated glial
      fibrillary acidic protein (GFAP)-expressing phenotype, and an up-regulation of
      the low-affinity NGF receptor p75NGFR on both RGC and Muller cells. NGF treatment
      of diabetic rats prevented both early PCD in RGC and Muller cells, and the
      development of pericyte loss and acellular occluded capillaries. CONCLUSIONS:
      These data provide new insight into the mechanism of diabetic retinal vascular
      damage, and suggest that NGF or other neurotrophic factors may have potential as
      therapeutic agents for the prevention of human diabetic retinopathy.

PMID- 8529119
TI  - Inhibition of protein phosphatase 1 stimulates secretion of Alzheimer amyloid
      precursor protein.
AB  - BACKGROUND: Aberrant metabolism of the Alzheimer amyloid precursor protein (APP)
      or its amyloidogenic A beta fragment is thought to be centrally involved in
      Alzheimer's disease. Nonamyloidogenic processing of APP involves its cleavage
      within the A beta domain by a protease, termed alpha-secretase, and release of
      the large extracellular domain, termed APPS. Secretion of APPS can be stimulated
      by phorbol esters, activators of protein kinase C, with concurrent inhibition of
      A beta production. While the role of protein kinases of APP metabolism has been
      investigated, considerably less effort has been devoted to elucidating the role
      played by protein phosphatases. Okadaic acid, a protein phosphatase inhibitor,
      has been shown to stimulate secretion of APPS, but the identity of the
      phosphatase involved has not been investigated. MATERIALS AND METHODS: The
      secretion of APPS from COS-1 cells was measured in the absence or presence of
      various doses of serine/threonine-specific phosphatase inhibitors. Quantitation
      of the derived IC50 values was used to determine the identity of the phosphatase
      involved in the control of APP secretion. RESULTS: The availability of protein
      phosphatase inhibitors with different relative potencies against the different
      types of serine/threonine-specific protein phosphatase allowed us to examine
      which of the four known types of protein phosphatase might be involved in the
      regulation of APP secretion. Both okadaic acid and calyculin A stimulated the
      secretion of APP from COS-1 cells in a dose-dependent manner. The half-maximal
      dose for stimulation of APP secretion was approximately 100-fold higher with
      okadaic acid than with calyculin A. CONCLUSIONS: The nearly 100-fold difference
      in the observed IC50 values for okadaic acid and calyculin A implicates a type 1
      protein phosphatase in the control of APPS production. Protein phosphatase 1
      (PP1) is known to be highly expressed in adult mammalian brain, both in neurons
      and glia. The identification of a specific phosphatase type in the control of APP
      secretion opens new avenues to the development of rational therapeutic
      intervention strategies aimed at the prevention and/or treatment of Alzheimer's
      Disease.

PMID- 8529120
TI  - Amyloid formation in response to beta cell stress occurs in vitro, but not in
      vivo, in islets of transgenic mice expressing human islet amyloid polypeptide.
AB  - BACKGROUND: Human, but not mouse, islet amyloid polypeptide (IAPP) is
      amyloidogenic. Transgenic mice overexpressing human IAPP in the beta cells of the
      islets of Langerhans should be useful in identifying factors important for the
      deposition of IAPP as insoluble amyloid fibrils. MATERIALS AND METHODS:
      Transgenic mice expressing human IAPP were examined using several experimental
      models for the production of persistent hyperglycemia, as well as for the
      overstimulation and/or inhibition of beta cell secretion. Obesity was induced by
      aurothioglucose. Persistent hyperglycemia was produced by long-term
      administration of glucocorticosteroids or by partial pancreatectomy. Inhibition
      of normal beta cell exocytosis by diazoxide administration, with or without
      concurrent dexamethasone injections, was carried out to increase crinophagy of
      secretory granules. The human IAPP gene was also introduced into the ab and ob
      mouse models for diabetes. Finally, isolated islets cultivated in vitro at high
      glucose concentration were also examined. RESULTS: No amyloid deposits were found
      in the pancreata of any of the animals, either by light microscopy after Congo
      red staining or by electron microscopy after immunogold labeling with antibodies
      specific for human IAPP. Aurothioglucose treatment resulted in increased numbers
      of granules in the beta cell and the appearance of large lysosomal bodies without
      amyloid. However, islets from db and ob mice expressing human IAPP cultivated in
      vitro in the presence of glucocorticosteroid and/or growth hormone, were found to
      contain extracellular amyloid deposits reacting with antibodies to human IAPP.
      CONCLUSIONS: Oversecretion of human IAPP or increased crinophagy are not
      sufficient for amyloid formation. This indicates that other factors must
      influence amyloid deposition; one such factor may be the local clearance of IAPP.

PMID- 8529122
TI  - Variable response to a candidate cancer vaccine antigen: MHC control of the
      antibody response in the rat to avian erythroblastosis virus (AEV)-encoded
      epithelial growth factor receptor but not AEV-encoded thyroid hormones receptor.
AB  - BACKGROUND: A problem likely to be encountered in any cancer immunotherapy based
      on vaccination with a single protein or peptide is variation in the host
      response. A particularly informative example is provided by the two oncogenic
      proteins, one intracellular and the other extracellular, encoded by the avian
      erythroblastosis virus (AEV), homologs of the thyroid hormones receptor (THsR)
      and the epithelial growth factor receptor (EGFR), respectively. MATERIALS AND
      METHODS: Antibodies to these two proteins were assayed by radioimmune
      precipitation (RIP) in sera from MHC-congenic rats immunized by virally induced
      tumors. RESULTS: Among the four haplotypes tested, RT1(1) rats exhibited a
      significantly lower response to the EGFR homolog than the high responders RT1c
      and RT1u, while RT1a rat strains had an intermediate response. Analysis of the
      recombinant haplotype RT1ac indicated that the response is controlled, as
      expected, by the class II locus of the MHC. In contrast, these rat strains
      responded uniformly to the intracellular THsR homolog. CONCLUSIONS: These results
      support the hypothesis that MHC restriction of the response to self-related
      proteins reflects mainly a tolerance mechanism. They sound a note of warning for
      cancer vaccine development, and also one of positive advice. The likelihood of
      MHC restriction suggests that a widely applicable polyvalent vaccine should be
      the final aim in cancer immunotherapy. Yet, paradoxically, evidence of MHC
      restriction can help establish that a candidate vaccine is likely to prove
      effective.

PMID- 8529121
TI  - Gamma delta T cell receptor analysis supports a role for HSP 70 selection of
      lymphocytes in multiple sclerosis lesions.
AB  - BACKGROUND: Interactions between gamma delta T cells and heat shock proteins
      (HSP) have been proposed as contributing factors in a number of diseases of
      possible autoimmune etiology but definitive evidence to support this hypothesis
      has been lacking. In multiple sclerosis (MS), a chronic inflammatory neurologic
      disease, HSP and gamma delta T cells are known to colocalize in brain lesions.
      Analysis of T cell receptor (TCR) gene usage in these lesions has detected
      evidence of clonality within both the V delta 2-J delta 1 and V delta 2-J delta 3
      populations of gamma delta T cells. In our own studies, using direct sequence
      analysis, a dominant V delta 2-J delta 3 TCR sequence was found in 9 MS brain
      samples, suggesting a response to a common antigen. In this report, we have
      examined gamma delta T cell receptor gene usage in MS peripheral blood T cell
      lines selected for reactivity to HSP 70. MATERIALS AND METHODS: TCR rearrangement
      patterns for V delta 2-J delta 1 and V delta 2-J delta 3 were studied using the
      polymerase chain reaction (PCR) and a direct sequencing technique in populations
      of peripheral blood mononuclear cells (PBMC) cultured with Mycobacterium
      tuberculosis (M. tuberculosis) purified protein derivative (PPD) and then
      selected for reactivity to a 70-kD heat shock protein (HSP70). Cells were
      obtained from health donors, patients with MS, and patients with tuberculosis
      (TB). PCR products were subjected to direct sequence analysis to look for
      evidence for clonality within these T cell lines and to define the sequence of
      the V-D-J (CDR3) region of the TCR. RESULTS: In freshly isolated PBMC, both V
      delta 2-J delta 1 and V delta 2-J delta 3 gene rearrangement patterns were
      detected, whereas in HSP70+ T cell lines the predominant delta chain
      rearrangement pattern was V delta 2-J delta 3. Direct sequence analyses indicated
      that in cells reactive with HSP70 the V delta 2-J delta 3 sequences were usually
      oligoclonal and used D delta 3 exclusively. In four of four MS and two of three
      TB patients, the oligoclonal sequences in the HSP70+ T cell lines were identical
      to one another and to a dominant sequence previously detected in MS brain
      lesions. In two of three HSP70+ T cell lines from healthy controls, the
      oligoclonal sequences differed from those found in both groups of patients but
      were identical to one another except for a small region of heterogeneity in the
      second N region. In contrast, in freshly isolated PBMC or in PPD+HSP70- T cell
      lines, the V delta 2-J delta 3 gene rearrangement patterns were usually
      polyclonal and dominant sequences were rarely identified. CONCLUSIONS: These
      results support the conclusion that a subpopulation of gamma delta T cells in MS
      lesions are responding to HSP 70 and that non-CNS-specific antigens contribute to
      the pathogenesis of MS.

PMID- 8529123
TI  - Ciliary neurotrophic factor inhibits brain and peripheral tumor necrosis factor
      production and, when coadministered with its soluble receptor, protects mice from
      lipopolysaccharide toxicity.
AB  - BACKGROUND: The receptor of ciliary neurotrophic factor (CNTF) contains the
      signal transduction protein gp130, which is also a component of the receptors of
      cytokines such as interleukin (IL)-6, leukemia-inhibitory factor (LIF), IL-11,
      and oncostatin M. This suggests that these cytokines might share common signaling
      pathways. We previously reported that CNTF augments the levels of corticosterone
      (CS) and of IL-6 induced by IL-1 and induces the production of the acute-phase
      protein serum amyloid A (SAA). Since the elevation of serum CS is an important
      feedback mechanism to limit the synthesis of proinflammatory cytokines,
      particularly tumor necrosis factor (TNF), we have investigated the effect of CNTF
      on both TNF production and lipopolysaccharide (LPS) toxicity. MATERIALS AND
      METHODS: To induce serum TNF levels, LPS was administered to mice at 30 mg/kg
      i.p. and CNTF was administered as a single dose of 10 micrograms/mouse i.v.,
      either alone or in combination with its soluble receptor sCNTFR alpha at 20
      micrograms/mouse. Serum TNF levels were the measured by cytotoxicity on L929
      cells. In order to measure the effects of CNTF on LPS-induced TNF production in
      the brain, mice were injected intracerebroventricularly (i.c.v.) with 2.5
      micrograms/kg LPS. Mouse spleen cells cultured for 4 hr with 1 microgram LPS/ml,
      with or without 10 micrograms CNTF/ml, were also analyzed for TNF production.
      RESULTS: CNTF, administered either alone or in combination with its soluble
      receptor, inhibited the induction of serum TNF levels by LPS. This inhibition was
      also observed in the brain when CNTF and LPS were administered centrally. In
      vitro, CNTF only marginally affected TNF production by LPS-stimulated mouse
      splenocytes, but it acted synergistically with dexamethasone (DEX) in inhibiting
      TNF production. Most importantly, CNTF administered together with sCNTFR alpha
      protected mice against LPS-induced mortality. CONCLUSIONS: These data suggest
      that CNTF might act as a protective cytokine against TNF-mediated pathologies
      both in the brain and in the periphery.

PMID- 8529125
TI  - Molecular medicine database.

PMID- 8529124
TI  - Analysis of families at risk for insulin-dependent diabetes mellitus reveals that
      HLA antigens influence progression to clinical disease.
AB  - BACKGROUND: Individuals at risk for insulin-dependent diabetes mellitus (IDDM),
      with an affected first-degree relative, can be identified by the presence of
      islet cell antibodies (ICA). ICA-positive relatives progress at variable rates to
      IDDM and identification of those at highest risk is a prerequisite for possible
      preventative treatment. Those who develop IDDM may exhibit less genetic
      heterogeneity than their ICA-positive or ICA-negative relatives. Specific human
      leucocyte antigen (HLA) genes predispose to IDDM but could also influence the
      rate of progression of preclinical disease. Therefore, by comparing HLA antigen
      frequencies between first-degree relatives, we sought to identify HLA genes that
      influence progression to IDDM. MATERIALS AND METHODS: HLA antigen frequencies
      were compared in 68 IDDM, 53 ICA-positive, and 96 ICA-negative first-degree
      relatives from 40 Caucasoid families. Predictions were tested in a panel of 270
      unrelated IDDM subjects. HLA typing was performed serologically (HLA class I and
      II) and by sequence-specific oligotyping (11th International Histocompatibility
      Workshop protocol) (HLA class II). ICA tests were measured by an internationally
      standardized indirect immunofluorescence assay. RESULTS: In general, known
      susceptibility class II HLA antigens increased in frequency and known protective
      class II HLA antigens decreased in frequency, from ICA-negative to ICA-positive
      to IDDM relatives. Thus, DR4 and DQ8 increased whereas DR2 and DQ6 decreased; DR3
      and DQ2 increased from ICA-negative to ICA-positive relatives, but not further in
      IDDM relatives. The high-risk DR3, 4 phenotype increased across the three groups;
      DR4,X was unchanged, and DR3,X and DRX,X both decreased. The HLA class I antigen,
      A24, occurred more frequently in ICA-positive relatives who developed IDDM and,
      in 270 unrelated IDDM subjects, was associated with an earlier age at diagnosis
      of IDDM in those with the lower risk class II phenotypes DR4,4 and DR3,X.
      CONCLUSIONS: HLA-DR3 and DQ2 predispose to islet autoimmunity, but not
      development of clinical IDDM in the absence and DR4 and DQ8. DR4 and DQ8
      predispose to the development of clinical IDDM in ICA-positive relatives, in
      combination with DR3-DQ2 and other haplotypes but not when homozygous. HLA-A24 is
      significantly associated with rapid progression to IDDM in ICA-positive relatives
      and with an earlier age at clinical diagnosis. Analysis of IDDM families reveals
      that HLA genes not only predispose to islet autoimmunity but influence
      progression to clinical disease. The findings have implications for identifying
      high-risk relatives as candidates for possible preventative therapy.

PMID- 8529126
TI  - Louis Pasteur and molecular medicine: a centennial celebration.

PMID- 8529127
TI  - Complete penetrance of Creutzfeldt-Jakob disease in Libyan Jews carrying the
      E200K mutation in the prion protein gene.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a prion disease which is manifest
      as a sporadic, inherited, and transmissible neurodegenerative disorder. The mean
      age at onset of CJD is approximately 60 years, and as such, many people destined
      to succumb undoubtedly die of other illnesses first. The delayed onset of CJD has
      complicated the analysis of inherited forms of the illness and led to the
      suggestion that mutations in the prion protein (PrP) gene are necessary but not
      sufficient for prion disease despite genetic linkage; indeed, an environmental
      factor such as a ubiquitous virus has been proposed as a second necessary factor.
      MATERIALS AND METHODS: To examine what appeared to be incomplete penetrance, we
      applied a life-table analysis to clinical and pedigree data from a cluster
      population of Libyan Jews in which the E200K mutation is prevalent. The study
      population included 42 affected and 44 unaffected members of 13 Libyan Jewish
      families, all of whom possessed the E200K mutation. RESULTS: The calculated value
      using life table analysis is 0.77 at age 70 which increases to 0.89 if a mutation
      carrier survives to age 80 and 0.96 if age 80 is surpassed. CONCLUSIONS: These
      data argue that the E200K mutation alone is sufficient to cause prion disease and
      does so in an age-dependent manner.

PMID- 8529128
TI  - Oligoclonality in the human CD8+ T cell repertoire in normal subjects and
      monozygotic twins: implications for studies of infectious and autoimmune
      diseases.
AB  - BACKGROUND: We have previously demonstrated CD8+ T cell clonal dominance using a
      PCR assay for the CDR3 length of T cell receptors belonging to a limited number
      of TCRBV segments/families. In this study, we have modified this approach in
      order to analyze more comprehensively the frequency of oligoclonality in the CD8+
      T cell subset in 25 known TCRBV segments/families. In order to assess the
      relative roles of genes and environment in the shaping of a clonally restricted
      CD8+ T cell repertoire, we have analyzed clonal dominance in the CD8+ T cell
      population of monozygotic twins, related siblings, and adoptees. MATERIALS AND
      METHODS: Oligoclonality was assessed in the CD8+ T cell subsets using a multiplex
      PCR approach to assay for CDR3 length variation across 25 different TCRBV
      segments/families. Specific criteria for oligoclonality were established, and
      confirmed by direct sequence analysis of the PCR products. This assay was used to
      investigate the CD8+ T cell repertoire of 56 normal subjects, as well as six sets
      of monozygotic (MZ) twins. RESULTS: Seventy-two percent of normal subjects (n =
      56) had evidence of oligoclonality in the CD8+ T cell subset, using well-defined
      criteria. Although MZ twins frequently displayed CD8+ T cell clonal dominance,
      the overall pattern of oligoclonality was very diverse within each twin pair.
      However, we occasionally observed dominant CD8+ T cell clones that were highly
      similar in sequence in both members of some twin pairs. Not a single example of
      such similarity was observed in normal controls or siblings. CONCLUSIONS:
      Oligoclonality of circulating CD8+ T cells is a characteristic feature of the
      human immune system; both host genetic factors and environment shape the pattern
      of oligoclonality in this T cell subset. The high frequency of this phenomenon in
      normal subjects provides a background with which to evaluate CD8+ T cell
      oligoclonality in the setting of infection or autoimmune disease. Further
      phenotypic and functional characterization of these clonally expanded T cells
      should provide insight into normal immune homeostasis.

PMID- 8529129
TI  - Similar peptides from two beta cell autoantigens, proinsulin and glutamic acid
      decarboxylase, stimulate T cells of individuals at risk for insulin-dependent
      diabetes.
AB  - BACKGROUND: Insulin (1) and glutamic acid decarboxylase (GAD) (2) are both
      autoantigens in insulin-dependent diabetes mellitus (IDDM), but no molecular
      mechanism has been proposed for their association. We have identified a 13 amino
      acid peptide of proinsulin (amino acids 24-36) that bears marked similarity to a
      peptide of GAD65 (amino acids 506-518) (G. Rudy, unpublished). In order to test
      the hypothesis that this region of similarity is implicated in the pathogenesis
      of IDDM, we assayed T cell reactivity to these two peptides in subjects at risk
      for IDDM. MATERIALS AND METHODS: Subjects at risk for IDDM were islet cell
      antibody (ICA)-positive, first degree relatives of people with insulin-dependent
      diabetes. Peripheral blood mononuclear cells from 10 pairs of at-risk and HLA-DR
      matched control subjects were tested in an in vitro proliferation assay. RESULTS:
      Reactivity to both proinsulin and GAD peptides was significantly greater among at
      risk subjects than controls (proinsulin; p < 0.008; GAD; p < 0.018). In contrast
      to reactivity to the GAD peptide, reactivity to the proinsulin peptide was almost
      entirely confined to the at-risk subjects. CONCLUSIONS: This is the first
      demonstration of T cell reactivity to a proinsulin-specific peptide. In addition,
      it is the first example of reactivity to a minimal peptide region shared between
      two human autoimmune disease-associated self antigens. Mimicry between these
      similar peptides may provide a molecular basis for the conjoint autoantigenicity
      of proinsulin and GAD in IDDM.

PMID- 8529130
TI  - Identification of galectin-3 as a high-affinity binding protein for advanced
      glycation end products (AGE): a new member of the AGE-receptor complex.
AB  - BACKGROUND: Advanced glycation end products (AGE), the reactive derivatives of
      nonenzymatic glucose-protein condensation reactions, are implicated in the
      multiorgan complications of diabetes and aging. An AGE-specific cellular receptor
      complex (AGE-R) mediating AGE removal as well as multiple biological responses
      has been identified. By screening an expression library using antibody against a
      previously identified component of the AGE-R complex p90, a known partial cDNA
      clone was isolated with homology to galectin-3, a protein of diverse identity,
      and member of the galectin family. MATERIALS AND METHODS: To explore this
      unexpected finding, the nature of the interactions between galectin-3 and AGE was
      studied using intact macrophage-like RAW 264.7 cells, membrane-associated and
      recombinant galectin-1 through -4, and model AGE-ligands (AGE-BSA, FFI-BSA).
      RESULTS: Among the members of this family (galectin-1 through 4), recombinant rat
      galectin-3 was found to exhibit high-affinity 125I-AGE-BSA binding with saturable
      kinetics (kD 3.5 x 10(7) M-1) that was fully blocked by excess unlabeled
      naturally formed AGE-BSA or synthetic FFI-BSA, but only weakly inhibited by
      several known galectin-3 ligands, such as lactose. In addition to the p90,
      immunoprecipitation with anti-galectin-3, followed by 125I-AGE-BSA ligand blot
      analysis of RAW 264.7 cell extracts, revealed galectin-3 (28 and 32 kD), as well
      as galectin-3-associated proteins (40 and 50 kD) with AGE-binding activity.
      Interaction of galectin-3 with AGE-BSA or FFI-BSA resulted in formation of SDS-,
      and beta-mercaptoethanol-insoluble, but hydroxylamine-sensitive high-molecular
      weight complexes between AGE-ligand, galectin-3, and other membrane components.
      CONCLUSIONS: The findings point toward a mechanism by which galectin-3 may serve
      in the assembly of AGE-R components and in the efficient cell surface attachment
      and endocytosis by macrophages of a heterogenous pool of AGE moieties with
      diverse affinities, thus contributing to the elimination of these pathogenic
      substances.

PMID- 8529131
TI  - Prevention of tumor formation in a mouse model of Burkitt's lymphoma by 6 weeks
      of treatment with anti-c-myc DNA phosphorothioate.
AB  - BACKGROUND: Transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion
      transgene (Emu-myc) provide a useful model for Burkitt's lymphoma. MATERIALS AND
      METHODS: Groups of 12 Emu-myc mice were treated prophylactically for 6 weeks
      after weaning with anti-c-myc DNA phosphorothioate (20 mg/kg/day), scrambled
      control DNA, or saline, delivered by micro-osmotic pumps. RESULTS: Half of the
      mice treated with saline or scrambled control DNA displayed palpable tumors by 8
      9 weeks after birth, and 95% of them did so by 16 weeks, but 75% of the mice
      treated with antisense DNA were still free of tumors at the age of 26 weeks.
      Antisense therapy ablated MYC antigen in the spleens of tumor-bearing mice.
      Plasma physiological parameters indicated no acute toxicity. CONCLUSIONS: Long
      term tumor resistance after anti-c-myc DNA therapy implies induction of a host
      response. Prophylactic anti-c-myc DNA therapy might prevent lymphoma in
      asymptomatic individuals displaying c-myc translocations.

PMID- 8529132
TI  - Association of elevated protein kinase CK2 activity with aggressive behavior of
      squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger
      independent protein serine/threonine kinase ubiquitously distributed in
      eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and
      nuclear substrates which are intimately involved in regulation of DNA, RNA, and
      protein synthesis, and differentiation. We therefore addressed the hypothesis
      that malignant transformation of upper aerodigestive tract mucosa to squamous
      cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2
      activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of
      SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We
      then quantitated CK2 activity in cytosol and nuclei of these specimens using a
      CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu).
      RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p
      < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to
      normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic
      fraction of SCCHN tumors was associated with less differentiated histologic grade
      (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical
      outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly
      reduced survival in the high-CK2 activity patient group, with high statistical
      significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that
      malignant transformation of the upper aerodigestive tract mucosa is associated
      with altered CK2 activity. The results further suggest that dysregulation of this
      protein kinase may play a significant role in the pathobiology of SCCHN, and that
      CK2 activity may be a prognostic indicator in this malignancy.

PMID- 8529133
TI  - Interleukin 1 induces HIV-1 expression in chronically infected U1 cells: blockade
      by interleukin 1 receptor antagonist and tumor necrosis factor binding protein
      type 1.
AB  - BACKGROUND: Cytokines and cytokine antagonists modulate human immunodeficiency
      virus (HIV) replication in vitro and may be involved in HIV disease pathogenesis.
      An understanding of these cytokine networks may suggest novel treatment
      strategies for HIV-seropositive persons. MATERIALS AND METHODS: U1 cells, a
      chronically infected promonocytic cell line, were stimulated with interleukin 1
      alpha (IL-1 alpha), IL-1 beta or tumor necrosis factor (TNF) for 24 hr. The
      effects of these cytokines, and of anti-IL-1 receptor type 1 and type 2 (IL-1RI
      and II) antibody, IL-1 receptor antagonist (IL-1Ra), and recombinant human TNF
      binding protein type 1 (rhTBP-1, a form of TNF receptor p55), on HIV-1
      replication, as measured by ELISA for HIV-1 p24 antigen, were determined. The
      effects of IL-1 and IL-1Ra on nuclear factor-kappa B (NF-kappa B) DNA binding
      activity, as measured by electrophoretic mobility shift assays, were also
      determined. RESULTS: IL-1 alpha and IL-1 beta increased p24 antigen production in
      a concentration-dependent manner. IL-1Ra completely, and rhTBP-1 partially,
      suppressed IL-1-induced p24 antigen production. IL-1 increased NF-kappa B DNA
      binding activity and IL-1Ra blocked this effect. Since IL-1Ra blocks IL-1 from
      binding to both the IL-1RI and Il-1RII, monoclonal antibodies directed against
      each receptor were used to ascertain which IL-1R mediates IL-1-induced HIV-1
      expression. Antibody to the IL-1RI reduced IL-1-induced p24 antigen production.
      Although anti-IL-1RII antibody blocked the binding of 125IL-1-1 alpha to U1 cells
      by 99%, this antibody did not affect IL-1-induced p24 antigen production. IL-1
      beta enhanced TNF alpha-induced HIV expression when added before or
      simultaneously with TNF alpha. CONCLUSIONS: IL-1 induces HIV-1 expression (via
      the IL-1RI) and NF-kappa B activity in U1 cells. These effects are blocked by IL
      1Ra and partially mediated by TNF. IL-1 enhances TNF alpha-induced HIV
      replication in U1 cells.

PMID- 8529137
TI  - Molecular medicine database.

PMID- 8529135
TI  - Interleukin 12: a potential link between nerve cells and the immune response in
      inflammatory disorders.
AB  - BACKGROUND: The nervous system has been implicated in several inflammatory skin
      disorders based on evidence such as the role of stress in inducing lesions,
      symmetry of lesions, and sparing of denervated skin. Interleukin 12 (IL-12) is a
      cytokine recently shown to promote cellular immune responses characterized by
      delayed-type hypersensitivity and production of the TH1-lymphokine, interferon
      gamma. MATERIALS AND METHODS: Using immunohistochemistry, IL-12 immunoreactivity
      was identified in cryostat sections of normal and diseased human skin samples,
      and in the peripheral and central nervous system of rodents and human tissue
      samples. IL-12 p35 and p40 mRNAs were detected using reverse transcriptase
      polymerase chain reaction in tissue samples and cultured cells. IL-12 protein
      levels were also examined by ELISA and quantitative bioassay utilizing an IL-12
      dependent cell line. RESULTS: By immunostaining IL-12 was detected in free nerve
      ending in the epidermis of normal and diseased skin samples, and also in the
      dermal nerve fibers. Strong reactivity was detected in axonal processes and in
      various glial cell types. In addition, IL-12 protein and mRNA were contained
      within cutaneous peripheral nerves and spinal cord tissues, and functional levels
      of IL-12 were produced by cultured Schwann cells. CONCLUSIONS: It is likely that
      IL-12 is important in initiating or propagating selected inflammatory skin
      lesions and in determining the pattern of disease that will develop. The presence
      of IL-12 in neural tissue suggests a mechanism whereby the nervous system can
      modify or amplify cutaneous and perhaps other immune responses.

PMID- 8529134
TI  - Delta opioidmimetic antagonists: prototypes for designing a new generation of
      ultraselective opioid peptides.
AB  - BACKGROUND: Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr
      Tic-Ala were the first peptides with delta opioid antagonist activity lacking
      Phe, considered essential for opioid activity based on the N-terminal tripeptide
      sequence (Tyr-D-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to
      restrain the rotational flexibility of Tyr by the substitution of 2,6-dimethyl-L
      tyrosine (Dmt). MATERIALS AND METHODS: Tyr and Dmt peptides were synthesized by
      solid phase and solution methods using Fmoc technology or condensing Boc-Dmt-OH
      or Boc-Tyr(But)-OH with H-L-Tic-OBut or H-D-Tic-OBut, respectively. Peptides were
      purified (> 99%) by HPLC and characteristics determined by 1H-NMR, FAB-MS,
      melting point, TLC, and amino acid analyses. RESULTS: H-Dmt-Tic-OH had high
      affinity (Ki delta = 0.022 nM) and extraordinary selectivity (Ki mu/Ki delta =
      150,000); H-Dmt-Tic-Ala-OH had a Ki delta = 0.29 nM and delta selectivity =
      20,000. Affinity and selectivity increased 8700- and 1000-fold relative to H-Tyr
      Tic-OH, respectively. H-Dmt-Tic-OH and H-Dmt-Tic-NH2 fitted one-site receptor
      binding models (eta = 0.939-0.987), while H-Dmt-Tic-ol, H-Dmt-Tic-Ala-OH and H
      Dmt-Tic-Ala-NH2 best fitted two-site models (eta = 0.708-0.801, F 18.9-26.0, p <
      0.0001). Amidation increased mu affinity by 10- to 100-fold and acted
      synergistically with D-Tic2 to reverse selectivity (delta-->mu). Dmt-Tic di- and
      tripeptides exhibited delta antagonist bioactivity (Ke = 4-66 nM) with mouse vas
      deferens and lacked agonist mu activity (> 10 microM) in guinea-pig ileum
      preparations. Dmt-Tic analogs weakly interacted with kappa receptors in the 1 to
      > 20 microM range. CONCLUSIONS: Dmt-Tic opioidmimetic peptides represent a highly
      potent class of opioid peptide antagonists with greater potency than the
      nonopioid delta antagonist naltrindole and have potential application as clinical
      and therapeutic compounds.

PMID- 8529138
TI  - Computers in nursing interactive.

PMID- 8529136
TI  - A mutation unique in serine protease inhibitors (serpins) identified in a family
      with type II hereditary angioneurotic edema.
AB  - BACKGROUND: Hereditary angioneurotic edema (HANE) is an autosomal dominant
      disease due to genetic alterations at the C1 inhibitor gene. Mutations within the
      C1 inhibitor gene are responsible for the molecular defect in type II HANE. Most
      of the dysfunctional proteins result from mutations involving the Arg-444 (the P
      1 site of the reactive center) or amino acids NH2-terminal to the reactive
      center. MATERIALS AND METHODS: We have studied a Spanish family with type II HANE
      by using polymerase chain reaction (PCR) to amplify the exon eight of the C1
      inhibitor gene. The purified 338-bp PCR product was subcloned and transformed
      into competent cells. After overnight cultures, we extracted the cloning vector
      from the positive colonies and sequenced both strands of the PCR product from
      each patient and healthy members of the family. RESULTS: We show that affected
      individuals in this family have a missense mutation, changing an adenine to
      cytosine in the codon 445. This substitution changes threonine at the P-1' site
      of the reactive center to a proline. This mutation generates a new restriction
      site, recognized by Bsi YI. CONCLUSIONS: To our knowledge, this is the first
      molecular defect characterized in a Spanish family with type II HANE, and to
      date, this is the first reported mutation at the P-1' site of the reactive center
      in individuals with type II HANE. This new mutation located at the reactive
      center emphasizes once more time the enormous heterogeneity of this gene.

PMID- 8529140
TI  - Using the Internet for data collection. An innovative electronic strategy.
AB  - Computer hardware and software have revolutionized research data management. Data
      collection has, however, remained a time-consuming and expensive component of
      most research projects. This article presents a description of an innovative
      strategy for data collection using computer network forums on the Internet (the
      "information superhighway"). The success of the electronic data collection
      strategy is illustrated by a report of the results of a survey of the needs and
      coping mechanisms of cancer survivors.

PMID- 8529139
TI  - Preparing nursing faculty for information-age teaching and learning.

PMID- 8529141
TI  - Evaluation of the impact of a bedside terminal system in a rapidly changing
      community hospital.
AB  - The impact of a bedside terminal system implemented in a community hospital was
      evaluated using a one-group before-and-after design. Contrary to predictions, the
      amount of time registered nurses spent in direct care and the positiveness of
      registered nurses' attitudes toward bedside terminal technology decreased after
      the implementation. Registered nurse overtime decreased in accordance with the
      prediction and unit medication errors remained unchanged. The internal validity
      of these results was threatened by organizational changes that directly and
      indirectly affected the study unit. Recommendations are made for conducting
      evaluation research in a rapidly changing hospital environment.

PMID- 8529142
TI  - A comparison of two methods of teaching. Computer managed instruction and keypad
      questions versus traditional classroom lecture.
AB  - Computers increasingly are being integrated into nursing education. One method of
      integration is through computer managed instruction (CMI). Recently, technology
      has become available that allows the integration of keypad questions into CMI.
      This brings a new type of interactivity between students and teachers into the
      classroom. The purpose of this study was to evaluate differences in achievement
      between a control group taught by traditional classroom lecture (TCL) and an
      experimental group taught using CMI and keypad questions. Both control and
      experimental groups consisted of convenience samples of junior nursing students
      in a baccalaureate program taking a medical/surgical nursing course. Achievement
      was measured by three instructor-developed multiple choice examinations. Findings
      demonstrated that although the experimental group demonstrated increasingly
      higher test scores as the semester progressed, no statistical difference was
      found in achievement between the two groups. One reason for this may be
      phenomenon of vampire video. Initially, the method of presentation overshadowed
      the content. As students became desensitized to the method, they were able to
      focus and absorb more content. This study suggests that CMI and keypads are a
      viable teaching option for nursing education. It is equal to TCL in student
      achievement and provides a new level of interaction in the classroom setting.

PMID- 8529143
TI  - Computerized support for case management ISAACC.
AB  - As the discipline of nursing strives to remain the logical orchestrator of case
      management, the ideal tool to support this effort would be based on a practice
      oriented nursing theory. One such theory, Self-Care Deficit Nursing Theory, has
      formed a base for a computerized system that has the potential to support case
      management. This article briefly describes the Professional Care System and the
      component of the system that can support case management: Intelligent System
      Access to Automated Clinical Charting (ISAACC) and plans for further expansion of
      the system.

PMID- 8529144
TI  - The development of automated client responses for computerized clinical
      simulation testing.
AB  - Computerized Clinical simulation Testing (CST) is under research and development
      by the National Council of State Boards of Nursing for potential use as a
      component of the National Council Licensure Examination for Registered Nurses.
      This interactive software permits the realistic assessment and management of
      client needs through free-text entry of requests for nursing activities.
      Implementation of each nursing activity elicits a realistic client response. A
      major component of the system is a default client response database that
      incorporates responses for 38 different client condition categories as well as
      rules for their automation. This article describes and illustrates the
      characteristics and complexity of this database that is designed to assist in the
      portrayal of realistic client situations.

PMID- 8529145
TI  - Short stay surgery replacing old systems.

PMID- 8529146
TI  - Diagnostic TMJ arthroscopy.
AB  - Temporomandibular joint arthroscopy has gained wide interest in recent
      literature. This article reviews the literature and describes equipment and
      techniques for diagnostic arthroscopy. Indications for diagnostic arthroscopy
      together with the possible intra- and postoperative complications are presented
      based on the authors own results. The diagnostic accuracy of temporomandibular
      joint arthroscopy is discussed.

PMID- 8529147
TI  - Arthroscopy of the human temporomandibular joint.
AB  - This paper reviews the indications, technique and results of arthroscopy of the
      human TMJ. Our results in arthroscopic treatment of 36 patients (48 joints) are
      reported and the results are comparable with previously reported results. Mainly
      internal derangements with closed lock and preauricular pain have been treated
      and in all cases a single puncture technique followed by a blunt sweep procedure
      was used. All patients have before arthroscopy received a conservative treatment
      with insufficient result. It is concluded that arthroscopy is an excellent tool
      in diagnosis and treatment of TMJ disorders. However TMJ arthroscopy should be
      regarded as a supplement to conventional therapy and an alternative to open joint
      surgery.

PMID- 8529148
TI  - Zygomatic fractures and infraorbital nerve disturbances. Miniplate osteosynthesis
      vs. other treatment modalities.
AB  - The present paper reviews the results obtained with different modalities of
      treatment employed in isolated fractures of the zygomatic complex. Seventy-three
      patients were re-examined with respect to infraorbital nerve function. The
      results obtained suggest that the incidence of hypoaesthesia of the infraorbital
      nerve following fracture of the zygomatic complex can be reduced if rigid
      fixation is applied on the infraorbital rim. The zygomatic bone is a protruding
      part of the human skeleton and is therefore easily affected by trauma to the
      facial region. The etiology and clinical appearance of fractures of the zygomatic
      complex are well known and previously described in detail (Afzelius and Rosen
      1980, Ellis et al. 1985, Jungell and Lindqvist 1987). Fractures of the zygomatic
      complex are rarely fractures of the zygoma itself but of its connection to the
      skull and facial skeleton, e.g. the frontozygomatic suture, the zygomatico
      maxillary suture, the zygomatic arch and the infraorbital rim. A fracture of the
      infraorbital rim usually involves the infraorbital foramen or bone close to it.
      Such a fracture also extends into the orbital floor through or adjacent to the
      infraorbital canal. Dislocation of the fractured zygomatic complex may thus
      result in injury to or compression of the infraorbital nerve. Such an injury may
      cause numbness/hypoaesthesia/dysaesthesia in the distribution of the nerve.
      Accordingly, reduced infraorbital nerve function is a frequently reported sequela
      of fractures of the zygomatic complex. Thus impaired infraorbital nerve function
      prior to treatment has been reported to occur in approximately 80% of such cases
      (Table 1). With respect to persistent impaired function of the infraorbital
      nerve, the literature demonstrates varying results following different types of
      treatment, ranging from 22% to 50% persistent hypoaesthesia (Table 1).
      Interestingly, the return of infraorbital nerve function continues with an
      extended observation period between treatment and follow-up and it has been
      claimed that infraorbital nerve function may continue to improve even after one
      year following injury/surgery (Afzelius and Rosen 1980). Cases with persistent
      and disturbing impaired function of the infraorbital nerve may be considered for
      decompressive nerve surgery or microsurgical reconstruction of the infraorbital
      nerve (Mozsary and Middleton 1983). The present report is a retrospective study
      and aimed to evaluate the recovery of infraorbital nerve function obtained with
      different modalities of treatment of isolated fractures of the zygomatic complex.

PMID- 8529149
TI  - Clinical and microbiologic comparisons of two dental implant systems.
AB  - Clinical soft tissue examination and microbiologic findings were compared for two
      dental implant systems. Of 20 edentulous patients, ten had been reconstructed
      with a transosteal implant of gold alloy, TMI-system (Bosker), of and ten with
      endosseous implants of titanium (Branemark-system). Clinical parameters evaluated
      included plaque, gingivitis, sulcus depth and bleeding on probing. Plaque samples
      from 14 patients were cultured for selected periodontal pathogens. Although some
      differences in soft tissue clinical behavior were identified, the incidence and
      prevalence of selected periodontal pathogens appeared to be similar.

PMID- 8529150
TI  - Treatment of mandibular fractures with or without intermaxillary fixation--a
      comparative study.
AB  - The aim of the present study was to evaluate titanium miniplates for treatment of
      mandibular fractures compared to routine treatment of the department (control).
      The study included 74 dentate patients with fractures within the tooth bearing
      regions of the mandible. Two groups of patients were studied:(A), 42 patients
      with unilateral fractures of the angle or anterior to the mental foramen and (B),
      32 patients with bilateral fractures of the mandible. Patients with unilateral
      fractures were randomized for the control group (n = 20) or the experimental
      group (n = 22). Group B included two groups of patients, a control group of 16
      consecutive patients previously treated, and an experimental group of 16
      consecutive prospectively studied patients. All patients in the control groups
      received open reduction and IMF for 5 weeks. Fractures of the angle were
      stabilized with an 0.4 stainless-steel wire superior border osteosynthesis,
      whereas fractures anterior to the mental foramen were treated with a stainless
      steel plate osteosynthesis. Patients in the experimental groups were treated with
      IMF only during surgery, thereafter the IMF was released. In fractures of the
      angle, one titanium mini-plate was used, whereas two were employed in fractures
      anterior to the mental foramen. The results were comparable in both groups with
      respect to occlusion and complications. We conclude that the titanium mini-plates
      offer sufficient stabilization of mandibular fractures to allow treatment without
      post-reduction IMF. This technique is associated with a low complication rate and
      reduced morbidity as compared to conventional treatment.

PMID- 8529151
TI  - Complications secondary to nasal tracheal intubation in oral surgery: report of
      three cases.

PMID- 8529152
TI  - Evaluation of surgical gloves for perforations following oral and maxillofacial
      surgery.
AB  - A study was performed to evaluate two types of sterile surgical gloves for
      perforations following oral and maxillofacial surgery. Our findings indicate that
      perforation of surgical gloves, and thus possible contamination of the surgeon
      and patient, is not uncommon, and to create a completely barrier-free environment
      when using sharp instruments may be impossible.

PMID- 8529153
TI  - The treatment of internal derangement of the temporomandibular joint--an
      arthroscopic approach.

PMID- 8529154
TI  - Hydroxyapatite implants: a rational approach.

PMID- 8529155
TI  - Very early vs. early or late surgery for infantile esotropia.

PMID- 8529156
TI  - Very early vs. early or late surgery for infantile esotropia.

PMID- 8529157
TI  - Vicryl-mesh wrap for the implantation of hydroxyapatite orbital implants: an
      animal model.
AB  - OBJECTIVE: To evaluate host fibrovascularization of hydroxyapatite orbital
      implants wrapped in sclera or in Vicryl (polyglactin 910) mesh in a rabbit model.
      NUMBERS: Eight adult New Zealand white rabbits that received hydroxyapatite
      orbital implants wrapped in homologous donor sclera (four animals) or Vicryl mesh
      (four animals). INTERVENTIONS: The rabbits had one eye enucleated and then
      received a 12-mm hydroxyapatite implant wrapped in sclera or Vicryl mesh.
      Magnetic resonance imaging (MRI) and bone scintigraphy were done to assess host
      fibrovascularization of the implant 4, 8, 12 and 20 weeks after implantation. Two
      animals (one in each group) were killed at each of these times, and the implant
      was removed for histopathological examination. MAIN OUTCOME MEASURES: Enhancement
      on MRI, uptake on bone scintigraphy, fibrovascularization seen on
      histopathological examination. RESULTS: The degree of fibrovascularization was
      substantial in all the specimens but appeared greater in the Vicryl-mesh-wrapped
      implants in the first 12 weeks after implantation on both histopathological and
      MRI studies. At 20 weeks these findings were similar in the two groups. A
      granulomatous foreign-body giant-cell reaction to both the Vicryl mesh and the
      implant itself was present up to 8 weeks after implantation. Bone scans showed
      only grade 1+ activity in all the implants. CONCLUSIONS: Host
      fibrovascularization in the rabbit appears to occur to a greater degree in Vicryl
      mesh-wrapped hydroxyapatite implants than in those wrapped in donor sclera during
      the first 12 weeks after implantation. Vicryl mesh appears to be an acceptable
      alternative wrap for the hydroxyapatite implant, eliminating the need for donor
      sclera and its potential risks of transmissible diseases.

PMID- 8529158
TI  - The 20-prism-dioptre base-out test: an indicator of peripheral binocularity.
AB  - OBJECTIVE: To assess the ability of the 20-prism-dioptre base-out test to detect
      the presence of peripheral fusion in children too young to undergo formal sensory
      testing. DESIGN: Case series. SETTING: Pediatric ophthalmology service at the
      Children's Hospital of Western Ontario, London. PATIENTS: Eighty orthophoric
      patients (mean age at presentation 19 months [range 4 to 50 months]) with a
      family history of strabismus or with a diagnosis of pseudostrabismus, blocked
      tear duct or chalazion, followed for an average of 36 (range 6 to 129) months,
      and 41 patients with surgically corrected infantile esotropia (mean age at
      testing with the 20-PD base-out test 21 months [range 9 to 50 months]), followed
      for an average of 53 (range 14 to 117) months. INTERVENTIONS: Twenty-PD base-out
      test and red-green Worth four-dot test at near (0.3 m). OUTCOME MEASURE: Presence
      of peripheral fusion. RESULTS: The 20-PD base-out test had a positive predictive
      value of 100% in detecting peripheral fusion in the orthophoric patients and 93%
      (95% confidence interval [CI] 82% to 100%) in the patients with surgically
      corrected infantile esotropia. CONCLUSIONS: Although the 20-PD base-out test had
      a negative predictive value of 21% (95% CI 0% to 43%), a positive response
      remains a useful indicator of peripheral binocular single vision in children too
      young to undergo more formal sensory testing.

PMID- 8529159
TI  - Microbial etiology and predisposing factors among patients hospitalized for
      corneal ulceration.
AB  - OBJECTIVE: To report the spectrum of microorganisms causing corneal ulceration in
      patients treated on an inpatient basis and to characterize the predisposing
      factors. DESIGN: Case series. SETTING: Large university-affiliated hospital in
      Toronto. PATIENTS: All inpatients with corneal ulcers managed between February
      1991 and February 1993 (n = 95). RESULTS: Coagulase-negative staphylococci (30%
      of the 60 culture-positive cases), Staphylococcus aureus (23%), Streptococcus
      pneumoniae (12%), Pseudomonas aeruginosa (12%) and Moraxella (7%) were the
      predominant isolates. Previous eye surgery (cataract extraction in 30 cases
      [32%], penetrating keratoplasty in 12 [13%] and both procedures in 9 [9%]) was a
      common predisposing factor. Eleven cases (12%) were associated with the use of
      contact lenses, in all cases extended-wear soft contact lenses; six patients wore
      bandage lenses and five wore contact lenses for cosmetic reasons. Pseudomonas was
      the predominant isolate among contact lens wearers (four cases). Most of the 95
      cases involved older patients (average age 62.5 years) with concomitant eye or
      systemic disease. Sixteen patients (17%) ultimately required penetrating
      keratoplasty. CONCLUSIONS: Recognition of the risk factors for corneal ulceration
      and prompt, intensive therapy are important to decrease the morbidity associated
      with this potentially blinding disease.

PMID- 8529160
TI  - Efficacy of four antiviral agents in the treatment of uncomplicated herpetic
      keratitis.
AB  - OBJECTIVE: To evaluate the efficacy of four antiviral agents--1% idoxuridine
      ointment (group 1), 2% trifluorothymidine ointment (group 2), 3% acyclovir
      ointment (group 3) and 1% bromovinyldeoxyuridine (BVDU) ointment (group 4)--in
      herpes simplex keratitis. DESIGN: Randomized double-blinded clinical trial.
      SETTING: Tertiary care institution in New Delhi. PATIENTS: Eighty patients with
      uncomplicated herpes simplex keratitis of recent onset who had not previously
      received antiviral treatment. MAIN OUTCOME MEASURES: Cure rate, frequency and
      severity of side effects. RESULTS: Cure rates of 60%, 90%, 90% and 95% were
      obtained in groups 1, 2, 3 and 4 respectively. The average healing time was 13.4,
      8.9, 8.5 and 7.5 days respectively. Side effects (follicular conjunctivitis,
      epithelial keratopathy and stinging) were more frequent in group 1 than in the
      other groups. CONCLUSIONS: BVDU has a more pronounced therapeutic effect than
      idoxuridine, trifluorothymidine and acyclovir in uncomplicated epithelial
      herpetic disease of recent onset that has not previously been treated.

PMID- 8529161
TI  - Medial rectus muscle weakness imitating a slipped muscle following medial optic
      nerve sheath decompression.

PMID- 8529162
TI  - Retrobulbar anesthesia with 7.5 vs. 0.75 IU/mL of hyaluronidase.

PMID- 8529163
TI  - The efficacy of topical corneal anesthesia with 0.5% bupivacaine eyedrops.

PMID- 8529164
TI  - One vs. two doses of 1.0% apraclonidine for prophylaxis of intraocular pressure
      spike after argon laser trabeculoplasty.

PMID- 8529166
TI  - Post-phaco endophthalmitis: on the increase?

PMID- 8529165
TI  - Bacterial keratitis in trichothiodystrophy.

PMID- 8529167
TI  - The interpretation of automated visual fields.

PMID- 8529168
TI  - Protection of the brain after aneurysmal rupture.
AB  - The majority of patients survive the first dangerous hours after an aneurysmal
      rupture. However, many subsequently succumb as a result of a variety of lethal
      complications. The most important of these develop as sequelae of the initial
      ischemia, rebleeding and the delayed onset of vasospasm. Some of these
      deleterious cascades can be aborted. Since the delayed complications such as
      vasospastic infarction can be accurately predicted, this is one of rare "strokes"
      that can have pharmacological pre-treatment. The natural history of rebleeding
      and vasospasm are described as well as their effects on blood flow, oxygen
      delivery and metabolism. Strategies to ameliorate acute and delayed ischemia and
      hypoxia are discussed. Finally, potential pharmacotherapies are detailed.

PMID- 8529169
TI  - Ruptured and unruptured intracranial aneurysms--surgical outcome.
AB  - BACKGROUND: The treatment of unruptured, intracranial aneurysms has been the
      topic of debate. Although recent studies have advocated surgical intervention for
      unruptured aneurysms, the risk of such treatment in comparison to outcome from
      ruptured aneurysms has not been established. METHOD: This retrospective study
      examines the outcome of 134 patients with 179 ruptured and unruptured
      intracranial, saccular aneurysms treated by a single surgeon. RESULTS: Of the 98
      ruptured aneurysms where early surgical intervention was undertaken (less than 48
      hours post hemorrhage), 70 had an excellent outcome, 13 were good, four were
      moderate, two poor and nine patients died postoperatively. Outcome assessment in
      these cases was correlated to preoperative neurological status. Patients who
      presented with unruptured aneurysms fell into two categories: symptomatic and
      asymptomatic. Seven incidental, asymptomatic aneurysms were clipped concurrently
      to the surgical isolation of the culprit lesion following subarachnoid hemorrhage
      without influencing outcome, whilst, for varying reasons, eight unruptured
      aneurysms were not operated upon. Of the remaining 66 surgically treated,
      unruptured aneurysms, 64 had an excellent postoperative result, one was good
      (persisting right incomplete third nerve palsy) and one was moderate (left
      hemiparesis). Thirteen of these aneurysms were symptomatic, whilst 21 were
      asymptomatic, multiple aneurysms requiring secondary elective repair and 32 were
      true incidental aneurysms. CONCLUSION: Unruptured aneurysms less than 25 mm in
      size may be safely, surgically treated relative to the expected natural history
      and, certainly, with less risk than operative intervention upon ruptured cerebral
      aneurysms.

PMID- 8529170
TI  - Nerve microvessel changes in diabetes are prevented by aldose reductase
      inhibition.
AB  - BACKGROUND: Despite the potential importance of endoneurial microvessel
      abnormalities in diabetic neuropathy, the pathogenesis of these abnormalities is
      incompletely understood. We wished to evaluate the effect of experimental
      diabetes on endoneurial microvessels and determine if an aldose reductase
      inhibitor alters any of the changes induced by diabetes. METHODS: We compared
      streptozocin diabetic rats with and without aldose reductase inhibitor treatment
      to non-diabetic rats after 10 months of diabetes. Transverse microvessels from
      the mid-sciatic level were studied by electron microscopic morphometric
      evaluation. RESULTS: Microvessel endothelial, pericyte, basement membrane and
      total mural area were greater in untreated diabetic animals than non-diabetic
      animals. Aldose reductase inhibitor treated diabetic animals had greater
      endothelial area and possibly pericyte area but not basement membrane or total
      mural area. CONCLUSIONS: This study demonstrates that endoneurial microvessel
      abnormalities can be detected in experimental diabetic neuropathy. Microvessel
      basement membrane thickening will be prevented by an aldose reductase inhibitor.
      One mechanism by which abnormal polyol pathway activity may contribute to
      diabetic neuropathy could be through damage to microvessels.

PMID- 8529171
TI  - Sulindac in established experimental diabetes: a follow-up study.
AB  - BACKGROUND: In two previous studies we have demonstrated prevention of
      electrophysiological abnormalities of nerve in experimental STZ (streptozotocin)
      induced diabetes (ED) of rats using nonsteroidal anti-inflammatory agents:
      indomethacin and sulindac. Sulindac might benefit ED because it inhibits both
      cyclo-oxygenase and aldose reductase. METHODS: In this work, we examined whether
      1 month of sulindac treatment reversed or improved established biochemical and
      electrophysiological abnormalities in experimental diabetes of 3 months duration.
      Sulindac-treated diabetic rats (6.0 mg/kg 5/7 days weekly by gavage) were
      compared to untreated diabetics, nondiabetic controls and sulindac treated
      control rats. RESULTS: Diabetic rats developed slowing of conduction velocity in
      caudal sensory, sural sensory, caudal motor and sciatic tibial motor fibers.
      Sulindac improved caudal motor and, to a lesser extent sural sensory conduction
      but not caudal sensory or sciatic tibial motor conduction. Sulindac did not alter
      sciatic sugars or polyols. CONCLUSIONS: Sulindac provided modest improvement in
      some indices of experimental neuropathy in this reversal study, but there was
      less efficacy than in the preventative study. Reversal paradigms should be
      examined in all experimental therapies for diabetic neuropathy.

PMID- 8529172
TI  - Experimental delayed postischemic spinal cord hypoperfusion after aortic cross
      clamping.
AB  - BACKGROUND: As in the brain, recent evidence has suggested a defect in the
      microcirculation during the reperfusion period after spinal cord ischemia. This
      investigation was undertaken in order to delineate blood flow dynamics in the
      postischemic spinal cord of the rat. METHODS: Male Sprague-Dawley rats underwent
      cross-clamping of the aorta and subclavian arteries (XC) for 11 minutes. Spinal
      cord blood flow (SCBF) was measured by autoradiography in the gray and white
      matter of cervical (Ce), thoracic (Th) and lumbar (Lu) regions during XC, 1 h, 6
      h and 24 h (XC n = 8, 1 h n = 9, 6 h n = 9, and 24 h n = 11, groups) after XC.
      Control groups underwent surgical manipulations and SCBF measurement but no XC
      (Sham 1, n = 8), or clamping of the subclavian arteries only (Sham 2, n = 8).
      RESULTS: In Ce cord, there was no difference between SCBF of 1 h, 6 h, 24 h and
      Sham 1. In Th cord, SCBF was reduced during XC (P < 0.003 vs. Sham 2), 1 h, 6 h
      (P < 0.04 and P < 0.01 vs. Sham 1). In Lu cord, SCBF was not detectable in XC,
      and depressed in 1 h (P < 0.003) and 6 h (P < 0.003). There was no difference
      between 24 h and Sham 1 in Ce, Th, and Lu cords. CONCLUSIONS: The study
      demonstrated a period of delayed postischemic hypoperfusion in the white and gray
      matter of Th and Lu cord segments lasting 6 h after XC. The phenomenon may play
      an important role in the ultimate fate of neural elements with borderline
      viability after ischemic injury.

PMID- 8529173
TI  - Long-term intrathecal baclofen therapy in patients with intractable spasticity.
AB  - BACKGROUND: Severe spasticity unresponsive to oral drugs may respond
      satisfactorily to baclofen delivered intrathecally. METHODS: Intrathecal baclofen
      (IB) therapy delivered by means of implanted infusion pumps was used for nine
      patients with severe spasticity. Six patients had multiple sclerosis, two
      cervical spinal cord injury, and one head injury. All were non-ambulatory.
      RESULTS: Patients showed improvement in many areas, including ability to
      transfer, seating, pain control, personal care, and liability to skin breakdown.
      Before IB therapy, only three of the nine patients were able to live at home in
      the community and six were institutionalized. At the end of our follow-up period,
      only one patient remained institutionalized, three lived in group homes and five
      lived at home in the community. In the year preceding pump implantation, the nine
      patients spent a total of 755 days in acute care hospitals. In the year following
      onset of IB therapy, they spent only 259 days in hospital. CONCLUSIONS: IB
      therapy can improve patient quality of life and can be cost-effective in
      carefully selected patients with severe spasticity and disability. The drug
      delivery catheter is that part of the therapeutic system most vulnerable to
      failure. Because of the varied expertise required to manage these patients
      effectively, and the potential for a variety of complications, it is essential
      that an IB program is supported by a well-organized multi-disciplinary medical
      team.

PMID- 8529174
TI  - The excitability of human corticospinal neurons is depressed by thiopental.
AB  - BACKGROUND: We tested the effect of thiopental on the excitability of the
      corticospinal-motoneuron axis in normal human subjects. METHODS: Magnetic
      stimulation was used to excite the neurons in the motor cortex which give rise to
      the fast conducting corticospinal pathway. The characteristics of the composite
      excitatory post-synaptic potentials (EPSPs) produced in individual spinal
      motoneurons by cortical stimulation were derived from changes in the firing
      probability of voluntarily activated motor units of the first dorsal interosseous
      muscle. RESULTS: In 5 normal subjects, we found that thiopental, in incremental
      doses sufficient to sustain drowsiness (total dose 75 to 175 mg), significantly
      reduced the amplitude of these composite EPSPs. CONCLUSIONS: Thiopental reduced
      the facilitation of motoneurons from the cortex most likely by depressing
      cortical neurons.

PMID- 8529175
TI  - An open trial of pyridostigmine in post-poliomyelitis syndrome.
AB  - BACKGROUND: One of the major symptoms of postpoliomyelitis syndrome (PPS) is
      disabling generalized fatigue. Subjects with PPS also report muscle fatiguability
      and display electrophysiologic evidence of anticholinesterase-responsive
      neuromuscular junction transmission defects, suggesting that anticholinesterase
      therapy may be useful in the management of disabling fatigue. METHODS: We
      initiated an open trial of the oral anticholinesterase pyridostigmine, up to 180
      mg per day, in 27 PPS patients with generalized fatigue and muscle fatiguability.
      Response to pyridostigmine was assessed with the Hare fatigue scale, the modified
      Barthel index for activities of daily living, and a modified Klingman mobility
      index. RESULTS: Two patients could not tolerate the medication. After one month
      of therapy, 16 patients (64%) reported a reduction in fatigue on the Hare fatigue
      scale; three of 16 showed improvement on the modified Barthel index for
      activities of daily living, and two of 16 experienced improvement on a modified
      Klingman mobility index. Pyridostigmine responders were significantly more
      fatigued than non-responders on the pre-treatment Hare score, but were not
      significantly different with regard to age, sex, age at acute poliomyelitis, or
      severity of acute poliomyelitis. CONCLUSIONS: Pyridostigmine may be useful in the
      management of fatigue in selected patients with PPS. Response to pyridostigmine
      may be predicted by severity of pre-treatment fatigue.

PMID- 8529176
TI  - Screening for major depression in the early stages of multiple sclerosis.
AB  - BACKGROUND: Multiple Sclerosis (MS) is associated with a high risk of developing
      major depression, but depression in MS patients frequently goes undetected and
      untreated. The current study examined the clinical utility of the Beck Depression
      Inventory (BDI) as a screening measure for major depression in newly diagnosed MS
      patients. METHODS: Forty-six new referrals to an MS clinic completed the BDI and
      participated in a structured interview for major depression, within 2 months of
      the diagnosis of MS. RESULTS: According to DSM-III-R criteria, 40% of patients
      were diagnosed with major depression, 22% had adjustment disorder with depressed
      mood, and 37% showed no evidence of mood disorder. Sensitivity and specificity
      values, and positive and negative predictive values are reported for every BDI
      cut-off score between 9 and 21. CONCLUSIONS: A BDI cut-off score of 13
      (sensitivity = .71, specificity = .79) is recommended as optimal for use in
      screening for major depression in newly diagnosed MS patients. The use of the BDI
      as a screening measure for major depression must proceed with caution given that
      a cut-off score of 13 still yielded a false-negative rate of 30%.

PMID- 8529177
TI  - Environmental exposures in elderly Canadians with Parkinson's disease.
AB  - BACKGROUND: Etiologic hypotheses for Parkinson's disease have implicated
      environmental factors, genetic factors, or a combination of the two. METHODS:
      Data from a survey of elderly Canadians (n = 10,263) with regard to their history
      of Parkinson's disease and previous environmental exposures were analyzed.
      Exposure to various environmental factors was compared between 87 patients with
      Parkinson's disease and 2070 elderly controls without Parkinson's disease.
      RESULTS: Exposure to plastic resins (OR (odd ratio) = 8.79), epoxy resins (OR =
      6.94), glues (OR = 4.26), paints (OR = 3.84), and petroleum (OR = 2.30) products
      was significantly (p < 0.05) associated with Parkinson's disease. CONCLUSION:
      These substances deserve further exploration with respect to the possible
      development of parkinsonism.

PMID- 8529178
TI  - Stereotactic insertion of an ommaya reservoir: technical note.
AB  - BACKGROUND: Stereotactic insertion of catheters into deep-seated tumors or
      developmental cysts is easily accomplished, but connecting the catheter to an
      Ommaya reservoir while maintaining catheter position can be difficult. We
      describe a technique for easy placement of a catheter-Ommaya reservoir construct
      with one pass. METHODS: Standard stereotactic imaging is performed. The distance
      from the outer table of the skull to the target point is measured. A catheter
      Ommaya reservoir construct is assembled to this length and directed to the target
      position with a standard Cosman-Robert-Wells (CRW) stereotactic frame. RESULTS:
      Use of this technique placed catheters into tumor or developmental cysts
      accurately and with no surgical complications in 12 patients. CONCLUSIONS: This
      technique is simple, safe, reliable, and requires no special equipment. It avoids
      the risk of dislodging the catheter when it is being connected to the Ommaya
      reservoir, reducing the chances of cyst leakage and collapse.

PMID- 8529179
TI  - "Unexplained" delayed death from fungal meningitis after meningioma resection.
AB  - BACKGROUND: Progressive deterioration and ensuing death following a neurosurgical
      procedure often represents a diagnostic challenge to the team responsible for
      patient care. Many, but not all, causes are treatable if a diagnosis is made
      early. METHODS: A 69-year-old woman who died 6 weeks post-operatively following a
      meningioma resection is reported. An initial routine post-operative course became
      complicated by progressive neurological deterioration 3-4 weeks later. Despite
      extensive investigation she died 6 weeks post-operatively without a diagnosis.
      RESULTS: Autopsy demonstrated extensive Candida meningitis. A review of the
      literature demonstrates this to be a reported complication in high risk patients,
      difficult to diagnose, but treatable when identified. CONCLUSIONS: Fungal
      meningitis should be high in the differential diagnosis in the post-operative
      patient with delayed, unexplained neurological deterioration, especially when
      associated with negative CSF cultures.

PMID- 8529181
TI  - What's in a name?

PMID- 8529180
TI  - Paradoxical autonomic response to procyclidine in the neuroleptic malignant
      syndrome.
AB  - BACKGROUND: Neuroleptic Malignant Syndrome (NMS) is an adverse reaction to
      dopamine receptor antagonists, characterised by hyperpyrexia, extrapyramidal
      rigidity and impaired autonomic function. It might result from central dopamine
      receptor blockade that causes severe muscle contraction. METHOD: Case Study.
      RESULTS: High dose intravenous therapy with the anticholinergic drug,
      procyclidine hydrochloride, temporarily diminished the muscle rigidity and
      reversed most of the autonomic features in a patient with NMS occurring after a
      single intramuscular dose of the dopamine antagonist metoclopramide.
      Paradoxically, however, the heart rate decreased and bowel movements increased
      with this atropine-like drug. CONCLUSION: Since the degree of tachypnoea,
      tachycardia, and bowel hypotonia closely paralleled the severity of the muscle
      rigidity, it is suggested that these autonomic features of NMS result from
      sustained muscle contraction rather than a direct effect of neuroleptic drugs on
      the central nervous system.

PMID- 8529182
TI  - Fee limits for general practitioners in BC.

PMID- 8529183
TI  - Episiotomy results stand despite lack of compliance.

PMID- 8529184
TI  - Pathologists: supply and demand.

PMID- 8529185
TI  - Proceedings of the 1994 Canadian Clinical Practice Guidelines Network Workshop.

PMID- 8529186
TI  - Physician-assessment and physician-enhancement programs in Canada.
AB  - Since the mid-1980s, the licensing authorities in Quebec, Ontario and Manitoba
      have introduced programs to conduct in-depth assessments of the clinical skills
      and abilities of physicians with suspected deficiencies. These assessments are
      intended to supplement the provincial licensing authorities' existing peer review
      or patient-complaint mechanisms by confirming the physicians' overall level of
      competence and identifying specific clinical strengths and weaknesses. An
      "educational prescription," based on the results of the assessment, focuses on
      aspects of clinical practice in which the physicians need or wish to enhance
      their skills. In some situations, licensure decisions are based on the assessment
      information. This article describes the programs in Quebec, Ontario and Manitoba.
      Each program comprises a different process of personal assessment and
      individualized continuing medical education to help physicians improve their
      clinical competence, and each is built on sound principles of clinical-competence
      assessment and educational planning.

PMID- 8529188
TI  - Necromancing the stones.
AB  - Since its introduction 15 years ago extracorporeal shockwave lithotripsy (ESWL)
      has become a standard treatment for urinary stones. The author comments on the
      results of Adrian R. Levy and Maurice McGregor's study of the use of ESWL for
      urinary stones in Quebec (see pages 1729 to 1736 of this issue). The rapid
      increase in the use of ESWL that occurred in the first 2 years of the study
      points to the fact that the application of a new technology is often quickly
      expanded before thorough assessments of effectiveness and safety have been
      carried out. New technologies also lead to shifts in cost distribution that must
      be considered in cost analyses. The author argues that continuing research is
      needed to document the dissemination of new technologies and points to
      methodologic concerns that should be addressed to make such research as fruitful
      as possible.

PMID- 8529187
TI  - How has extracorporeal shock-wave lithotripsy changed the treatment of urinary
      stones in Quebec?
AB  - OBJECTIVES: To determine the number of people who underwent treatment of urinary
      stones in Quebec before and after the introduction of extracorporeal shock-wave
      lithotripsy (ESWL) and to determine how the introduction of ESWL influenced
      resource utilization. DESIGN: Before-after study; data were obtained from
      administrative databases and hospital-based cost estimates. SETTING: The 68 acute
      care hospitals in Quebec in which treatment of urinary stones is undertaken.
      PATIENTS: Quebec residents admitted to hospital for treatment of urinary stones
      between the fiscal years 1984 and 1992. OUTCOME MEASURES: Number of people
      treated for urinary stones per year, total number of procedures per year
      (including open surgery, percutaneous procedures, retrograde procedures and
      ESWL), and annual resources (including number of hospital bed-days and direct
      costs) for treatment of urinary stones used overall and in hospitals with and
      without ESWL services. RESULTS: Over the study period the number of people
      treated for urinary stones increased by 59%. As well, the combined frequency of
      ESWL and surgery (the two main treatment methods) increased by 107%. These
      increases were largely due to rates of treatment that grew by 52% among women and
      by 34% among men. The total number of hospital bed-days decreased by 28%, which
      reflected shorter hospital stays for ESWL. However, despite this decrease, the
      total direct annual costs were 7% higher in 1992 than in 1984 because of the
      increased numbers of people treated and procedures performed. In the three
      hospitals that offered ESWL the number of hospital bed-days and the direct costs
      of treating urinary stones increased by 49% and $2.5 million respectively. In the
      65 other hospitals these figures decreased by 41% and about $2.9 million
      respectively. CONCLUSIONS: Because of increased intervention rates the total cost
      of treating urinary stones has risen since the introduction of ESWL. The
      introduction of ESWL has also been associated with a shift in the use of
      resources for treating urinary stones to hospitals with a lithotriptor. The
      reasons for the increased intervention rates are unknown. However, given the
      possibility of negative health effects and the increased costs, studies to
      determine whether the increased rates improve health outcomes are warranted.

PMID- 8529189
TI  - Premature babies and pharmacology.
AB  - In his research on the action of various drugs in newborns, Dr. Jacob Aranda of
      the Centre for Perinatal and Developmental Pharmacology Research in Montreal
      draws upon his expertise in both neonatology and pharmacology. His work has led
      to the acceptance of caffeine as a standard treatment of apnea in premature
      infants, and his current studies of ibuprofen as a possible treatment of cerebral
      intraventricular hemorrhage, a serious problem in some premature babies, have
      yielded promising results. Other areas being tackled by Aranda and his colleagues
      include pain control for newborns and the elusive pathology of sudden infant
      death syndrome. By shedding more light on neonatal development and the principles
      of drug action in newborns, these research projects will help to improve the odds
      for many babies who suffer the setback of being born too soon.

PMID- 8529190
TI  - AIDS networking in Canada, US.

PMID- 8529191
TI  - Changes in Canada pension plan disability rules hold implications for physicians.
AB  - Recent legislative changes to the Canada Pension Plan (CPP) have significantly
      altered eligibility requirements for disability pensions. A CPP medical adviser
      explains how the changes affect physicians and examines the federal government's
      definition of "disability."

PMID- 8529192
TI  - Scientific presentations at Royal College meeting take look at medicine's bottom
      line.
AB  - Attempts to get good results from fewer health care dollars received considerable
      attention during the recent annual meeting of the Royal College of Physicians and
      Surgeons of Canada. Pam Harrison provides an overview of some research findings
      presented during the meeting, held in Montreal.

PMID- 8529193
TI  - Occupational injuries, illness affect 1 in 13 Canadians.
AB  - One in every 13 Canadian workers has experienced a work-related illness or
      injury, federal data indicate. Occupational-health clinics in Ontario report a
      growing number of cases of sick-building syndrome, repetitive-strain injury,
      asthma and chemical exposure, as well as injuries related to the use of
      construction equipment. In the past the medical profession assumed that men
      incurred most work-related injuries, but today, says an occupational-health
      specialist, "work-related illness and injuries are just as likely to happen to
      women or to white-collar professionals."

PMID- 8529194
TI  - US guidelines for treatment of schizophrenia expected next year.
AB  - The American Psychiatric Association (APA) is developing new guidelines for
      treating schizophrenia. The recommendations, which were previewed at the APA's
      annual meeting earlier this year, are expected to be released in 1996.

PMID- 8529195
TI  - Physicians should keep an open mind on complementary health care, Congress says.
AB  - Three hundred physicians from Canada and abroad attended the 3rd World Congress
      of Medical Acupuncture and Natural Medicine held in Edmonton last summer.
      Speakers emphasized that physicians should view complementary health care
      services with an open mind and consider therapeutic options that may be used in
      addition to conventional medical therapy.

PMID- 8529196
TI  - Changes in GTP-dependent fusion and ras-related proteins in membranes from rat
      hepatocellular carcinomas.
AB  - The fusion capacity of rough endoplasmic reticulum membranes isolated from
      dissected liver tumor nodules of aflatoxin-treated rats was determined by cell
      free assay to be greater than that of homologous membranes from control liver. In
      a first attempt to understand the reason for this difference we compared the
      content of ras-related proteins in rough microsomal fractions and other cell
      fractions of both dissected tumor nodules and control liver. Using [alpha-32P]GTP
      blot overlay and densitometric analysis, homogenate, Golgi and rough endoplasmic
      reticulum fractions from dissected tumor nodules were observed to contain
      increased amounts of [alpha-32P]GTP binding to ras-related proteins when compared
      to homologous control fractions. Western blot analysis indicated that ras content
      was also increased in the tumor fractions. [alpha-32P]GTP-blot overlay using
      double-dimensional SDS-polyacrylamide gel electrophoresis confirmed quantitative
      differences in the amount of [alpha-32P]GTP binding to ras-related proteins
      between fractions from tumor and control tissues and indicated a surprising
      number of such proteins in each fraction. The data suggest that the changes in
      ras-related proteins could, in part, account for the enhanced GTP-dependent
      fusion capacity observed for the tumor-derived membranes.

PMID- 8529197
TI  - Differential sensitivity of human prostatic cancer cell lines to the effects of
      protein kinase and phosphatase inhibitors.
AB  - We investigated the effect of protein kinase and phosphatase inhibitors on the
      growth of six human prostatic cancer cell lines: DU145, PC3, ND1, LNCaP, ALVA31
      and JCA1. We studied okadaic acid and sodium orthovanadate as serine/threonine
      and tyrosine protein phosphatase inhibitors, respectively, and staurosporin and
      genistein as a serine/threonine and tyrosine protein kinase inhibitors,
      respectively. All inhibitors examined exhibited a dose-dependent growth
      inhibitory effect on prostatic cancer cell lines. Our data indicate that
      prostatic cancer cell lines express unique biochemical properties since the
      degree of growth inhibition varied greatly and was dependent on the specific cell
      line and inhibitor studied. In addition, we found that surface expression of
      endoglin (CD105) changed by treatment with all inhibitors in most of the cell
      lines. These data also indicate that endoglin appears to be involved both in
      protein phosphatase and kinase mediated phosphoprotein turnover.

PMID- 8529198
TI  - H1 histone sub-type distribution and DNA topoisomerase activity in skeletal
      muscle of tumour-bearing rats.
AB  - In an investigation of possible causes of the transcriptional defect which has
      been observed in muscles atrophying in response to tumour growth, the amounts of
      histone H1 subtypes and the activities of DNA topoisomerase I and II, factors
      which can affect the structural organisation of chromatin, were studied in nuclei
      of skeletal muscle of rats bearing a Walker 256 carcinoma. The H1 histones were
      separated by SDS/PAGE into three fractions, H1.1, H1.2 and H1(0). The level of
      H1.2 but not that of H1.1 or H1(0) was increased in the tumour-bearing animal.
      Tumour growth did not affect the activity of either DNA topoisomerase I or II.

PMID- 8529199
TI  - Gain and loss of hypersensitivity to resistance modifiers in multidrug resistant
      Chinese hamster ovary cells.
AB  - Some, but not all, multidrug resistant cell lines exhibit collateral
      hypersensitivity to resistance modifiers. We have examined the relationship
      between levels of P-glycoprotein expression and resistance modifier
      hypersensitivity in Chinese hamster ovary cell lines. We have defined a model
      system for the gain and loss of such sensitivity which indicates that its
      presence is not simply proportional to P-glycoprotein levels, but is acquired
      only above a certain level of P-glycoprotein expression. We also show that
      previously reported differences in such sensitivity between lines is not
      attributable to differences in genetic background of the cell lines used for
      selection of drug resistance.

PMID- 8529200
TI  - HLA-A, B, C, DR and DQ expression and hepatocellular carcinoma: study of 205
      Italian subjects.
AB  - We have evaluated the frequency of HLA class I and II antigens in 205 Italian
      patients with hepatocellular carcinoma (HCC) and 749 blood donors (controls).
      Moreover, we have looked for correlations between HLA antigen frequencies and HBV
      and/or HCV infections in HCC patients. We found great differences in HLA antigen
      frequencies considering only two groups: HCC patients and controls. The
      polymorphism is smaller when we consider the different groups of HCC patients in
      regard to the previous viral infections (HBV and/or HCV). The most interesting
      finding is the higher frequency of Cw7, B8 and DR3 in almost all groups of HCC
      patients. It is well known, that the HLA A1, Cw7, B8, DR3 antigen haplotype is
      associated with a rapid decline of CD4 cells, and HLA B8, DR3 positive subjects
      may display some changes in immune parameters and are prone to develop several
      immunological diseases. Thus HCC might be the result of a lower sensitivity
      (genetically given) to mitogenic stimuli of HBV and HCV.

PMID- 8529201
TI  - The effects of calcium antagonists on anthrone skin tumor promotion and promoter
      related effects in SENCAR mice.
AB  - The present study investigated a possible role for Ca2+ in skin tumor promotion
      by anthrones. This was accomplished by testing the effects of two Ca2+
      antagonists, verapamil and 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl
      ester (TMB-8), on tumor promotion and promoter-related effects induced by the
      anthrone chrysarobin in SENCAR mice. Verapamil and TMB-8 both effectively
      inhibited epidermal ornithine decarboxylase (ODC) induction by a single
      application of chrysarobin. Both Ca2+ antagonists inhibited anthrone-induced skin
      edema and epidermal hyperplasia. Additionally, both verapamil and TMB-8 slightly
      inhibited (20-21% at the highest doses) tumor promotion with chrysarobin.
      Although the inhibition by both Ca2+ antagonists was not statistically
      significant (P > 0.05) in either case, the fact that both compounds produced a
      similar inhibition suggests that this effect may be biologically relevant.
      Collectively, the data suggest a possible role for Ca2+ in the process of skin
      tumor promotion by anthrones.

PMID- 8529202
TI  - Inhibitory effects of green tea infusion on in vitro invasion and in vivo
      metastasis of mouse lung carcinoma cells.
AB  - The peroral administration of green tea infusion reduced the number of lung
      colonies of mouse Lewis lung carcinoma cells in a spontaneous metastasis system.
      The experiments with artificially reconstituted basement membrane suggested that
      this reduction could be understood by the inhibitory effects of the green tea
      infusion and its constituent catechins on the penetration of the cells through
      the basement membrane.

PMID- 8529203
TI  - Non-homogeneous marking of distal colonic mucosa using Dolichos biflorus lectin.
AB  - A carbohydrate polymorphism that is restricted to the intestinal epithelium and
      vascular endothelium has been observed in a panel of inbred mouse lines,
      including the SWR/J (endothelium positive, epithelium negative) and DBA/2J
      (reverse pattern). This carbohydrate polymorphism is recognized by the conjugated
      lectin, Dolichos biflorus agglutinin (DBA), and has been used to examine the
      clonality of intestinal cells in mouse aggregation chimeras. The SWR/J (tumor
      susceptible) and DBA/2J (resistant) mouse lines are important models for the
      study of chemically induced colorectal cancer. To extend these earlier findings
      to several additional inbred mouse lines that exhibit widely different genetic
      susceptibilities to the carcinogenic properties of colon carcinogen, 1,2
      dimethylhydrazine (DMH), we undertook a study to examine DBA binding in the
      colonic epithelium of four inbred mouse lines (AKR/J, P/J, SWR/J and DBA/2J). DBA
      binding was examined in discrete regions of the colon (proximal, middle and
      distal). In SWR/J mice, DBA binding was not altered in colon tissue from a DMH
      treated mouse exhibiting early dysplastic changes, suggesting the usefulness of
      this marker for studying clonal descent of early neoplastic tissue in chimeras.
      Interestingly, DBA marking patterns became non-homogeneous in a proximal to
      distal orientation in the AKR/J and P/J mice. These findings with DBA are
      discussed in terms of the usefulness of this cellular marker as a method of
      establishing clonal descent in carcinogen treated mouse aggregation chimeras.

PMID- 8529204
TI  - Early initiating and promoting effects in 2-AAF-induced rat liver carcinogenesis:
      an immunohistochemical study.
AB  - 2-Acetylaminofluorene (2-AAF) is a complete carcinogen in rat liver. To
      investigate the specific properties, that distinguish 2-AAF from incomplete
      carcinogens, rats were fed 0.02% AAF in the diet for 6, 12, 16 weeks and some
      indicators of genotoxic and chronic toxic effects were studied
      immunohistochemically. GST-P, a marker for single initiated cells and
      preneoplastic foci, was induced in response to 2-AAF exposure. The effects were
      slight after 6 weeks of feeding, after 12 weeks GST-P-positive preneoplastic foci
      were present. The proto-oncogenes c-fos and c-jun are induced by several tumor
      promoters. In the present study c-FOS protein levels were increased in all 2-AAF
      treated animals at early stages not only in preneoplastic foci. However, all GST
      P-positive foci were also c-FOS-positive. Surprisingly c-JUN was not enhanced in
      GST-P positive foci. It was comparatively expressed in hepatocytes and bile duct
      cells in all animals. We did not observe any immunolabeling for p53, either in
      preneoplastic foci or in hepatocytes from treated animals. A significant increase
      of apoptoses was noted in the whole liver lobule but also gathered in groups in
      the periportal area. The results support our proposal that oxidative stress and
      energy impairment in the mitochondria of periportal hepatocytes trigger
      morphological alterations in the rat liver.

PMID- 8529205
TI  - Effect of site-specifically located aristolochic acid DNA adducts on in vitro DNA
      synthesis by human DNA polymerase alpha.
AB  - In order to examine the effect of purine adducts of the plant carcinogen
      aristolochic acid (AA) on DNA replication four 30-mer templates were prepared
      which contained single site-specific AA lesions. The oligonucleotides were
      isolated by HPLC and shown to contain the two known aristolochic acid I-DNA
      adducts (dA-AAI, dG-AAI) or the two known aristolochic acid II-DNA adducts (dA
      AAII, dG-AAII) at position 27 from the 3' end by 32P-postlabeling. These adducts
      templates were replicated in primer (23-mer) extension reactions catalysed by
      human DNA polymerase alpha. Both AAI-DNA adducts (dA-AAI, dG-AAI) blocked DNA
      synthesis predominantly (80-95%) at the nucleotide 3' to the adduct, although
      primer extension to the full length of the template was found with unmodified
      control templates. Increasing dNTP concentrations had only a small effect on the
      DNA synthesis and translesional synthesis was negligible. In contrast, both AAII
      DNA adducts showed marked differences in primer extension reactions. Blocking of
      DNA synthesis by the dA-AAII adduct was strongly dNTP dependent. With increasing
      dNTP concentrations 27 and 28 nucleotide products, indicating termination of DNA
      synthesis after incorporation of a nucleotide opposite this adduct and
      incorporation of an additional nucleotide accumulated. Only the dG-AAII adducted
      template allowed substantial translesional synthesis to the full length of the
      template (up to 25%). When a 26-mer primer was used to examine nucleotide
      incorporation directly across from the four purine adducts, we found no
      detectable incorporation of nucleotides for the dA-AAI adduct, whereas the dG-AAI
      adduct and both AAII-adducts (dA-AAII and dG-AAII) allowed preferential
      incorporation of the correct nucleotide. These results indicate that for human
      polymerase alpha three AA purine adducts (dA-AAI, dG-AAI and dA-AAII) provide
      severe blocks to DNA replication and that dG-AAII, which allows translesional
      synthesis, may not be a very efficient mutagenic lesion.

PMID- 8529206
TI  - Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone
      receptor mRNAs in various non-reproductive human tissues.
AB  - Recently, cloning of the gonadotropin-releasing hormone (GnRH) receptor from the
      human breast tumor cell line (MCF-7) and from an ovarian tumor, and its
      expression in various other human tumors, tumor cell lines and reproductive
      organs have been reported (Kakar et al., Mol. Cell. Endocrinol., 106 (1994) 145
      149). In the present studies, we investigated the expression of GnRH and GnRH
      receptor mRNAs in normal human non-reproductive tissues. Using reverse
      transcriptase-polymerase chain reaction (RT-PCR) techniques and specific
      oligonucleotide primers derived from the placental GnRH cDNA sequence, PCR
      products of the expected size were obtained from human liver, heart, skeletal
      muscle, kidney, placenta, and pituitary. The authenticity of the PCR products was
      confirmed by Southern blot analysis with an internal oligonucleotide primer as
      probe. Similarly, using specific oligonucleotide primers for the GnRH receptor
      selected from the human pituitary GnRH receptor cDNA sequence, PCR products of
      the expected size were amplified from human liver, heart, skeletal muscle,
      kidney, placenta, and pituitary, and these strongly hybridized with the human
      GnRH receptor cDNA on Southern blot. Cloning and nucleotide sequencing of the PCR
      products for the GnRH and GnRH receptor from heart revealed identical sequences
      when compared to the human placental GnRH and pituitary GnRH receptor cDNAs,
      respectively. These data demonstrate for the first time the existence of GnRH and
      GnRH receptor mRNAs in normal human non-reproductive tissues and suggest that
      GnRH and its receptor may play an important role in the regulation of cellular
      functions in an autocrine or paracrine manner, in addition to regulating the
      secretion of gonadotropins from the anterior pituitary.

PMID- 8529207
TI  - Induction of NAD(P)H:quinone reductase by vitamins A, E and C in Colo205 colon
      cancer cells.
AB  - High consumption of fruits and vegetables which are abundant in dietary
      antioxidants has been linked to a reduced incidence of colorectal cancer. A
      potential mechanism of dietary anticarcinogenesis involves the induction of
      detoxifying phase II enzymes, including NAD(P)H:quinone reductase (QR) and
      glutathione-S-transferase (GST). This study therefore examined the ability of the
      dietary antioxidant vitamins beta-carotene, alpha-tocopherol and ascorbic acid to
      induce cellular expression of QR and GST activities in human colon cancer cells.
      Colo205 cells were cultured in the presence or absence of various concentrations
      (10(-10) to 10(-5) M) of each antioxidative micronutrient, then assessed for
      cytosolic QR and GST activities and cell growth. beta-Carotene, alpha-tocopherol
      and ascorbic acid each resulted in dose-dependent increases in QR activity,
      without adverse effects upon cell proliferation. To investigate whether the
      ability of beta-carotene to induce QR may be attributable to its conversion to
      vitamin A and/or to its antioxidant capacity as a carotenoid, retinol, retinoic
      acid, and lycopene were similarly tested for their capacity for enzyme induction.
      Although retinol and retinoic acid were both noted to be antiproliferative at
      higher concentrations (10(-6) to 10(-5) M), both retinoids stimulated QR at
      physiological concentrations. Lycopene, a carotenoid which is not converted to
      vitamin A, was devoid of biologic activity. By contrast with the effects upon QR,
      GST activity was unaffected by treatment with any of the micronutrients tested in
      this in vitro model. The results support a hypothesis that a high dietary
      consumption of vitamins A, E and C may confer partial protection against
      colorectal cancer by the induction of specific detoxifying enzymes. The
      antioxidant capacity of beta-carotene appears to have less biologic impact vis-a
      vis QR induction than its function as a non-toxic reservoir of vitamin A.
      Measurements of QR activity within the colorectal mucosa may provide an index of
      cancer susceptibility, and may be an appropriate surrogate endpoint biomarker for
      colorectal cancer prevention studies involving diet modification or specific
      relevant micronutrients.

PMID- 8529208
TI  - Enhancement of GST-P positive liver cell foci development by a medium-term
      carcinogenicity bioassay using repeated administration of D-galactosamine.
AB  - This study was performed for developing a new medium-term carcinogenicity
      bioassay treated with D-galactosamine (DGA) as a non-surgical method without
      partial hepatectomy (PH). In male F344 rats initiated with diethylnitrosamine
      (DEN, 200 mg/kg i.p.), enhancing effects of DGA (300 mg/kg i.p.) given twice 3
      weeks apart during the promotion procedure with 2-acetylaminofluorene (2-AAF,
      0.01% in diet) were compared along with those of PH by analyzing preneoplastic
      glutathione S-transferase placental form positive (GST-P+) hepatocyte foci as
      endpoint marker lesions. The DGA treatment did not affect the body weight gain
      whereas the PH treatment caused a transient body weight loss. Although both
      bioassay protocols were effective to detect the potential hepatocarcinogenicity
      of 2-AAF, the number and area of GST-P positive foci per cm2 were larger in the
      bioassay using DGA than in that using PH, the number being statistically
      significant (P < 0.05). Our results thus suggest 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 carcinogens.

PMID- 8529209
TI  - Growth factor-independent expression of the gene encoding eukaryotic translation
      initiation factor 4E in transformed cell lines.
AB  - Activation of protein synthesis is necessary for the transition of cells from
      quiescence to proliferation, while withdrawal of growth factors leads to decrease
      in protein synthesis and transition of normal cells into the resting period. It
      is shown in this paper that serum growth factors are required for activation of
      expression of gene encoding translation initiation factor 4E (eIF-4E) in non
      transformed NIH 3T3 and Rat-1 fibroblasts but this requirement is lost in C6
      glioblastoma, A431 carcinoma and N-myc transformed Rat-1 cells. These data raise
      the possibility that neoplastic transformation leads to growth factor-independent
      expression of eIF-4E, thus facilitating continuous growth and replication of
      transformed cells.

PMID- 8529210
TI  - Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted
      fibrosarcoma growth in the rat.
AB  - In the presence of iron, dihydroartemisinin forms free radicals and causes cell
      death. Since most cancer cells have high rates of iron intake, dihydroartemisinin
      would have selective cytotoxic effect on cancer cells. The present experiment was
      designed to study the effect of dihydroartemisinin and ferrous sulfate on the
      growth of implanted fibrosarcoma in the rat. We found that the growth rate of the
      tumor was significantly retarded by daily oral administration of ferrous sulfate
      followed by dihydroartemisinin. No significant tumor growth retardation effect
      was observed in rats treated with either dihydroartemisinin or ferrous sulfate
      alone. The drug treatment did not significantly affect body weight compared with
      untreated tumor-implanted animals and no apparent toxic effect was observed after
      drug treatment. An artemisinin analog-ferrous salt combination may provide a
      novel approach for cancer therapy.

PMID- 8529211
TI  - Increased invasive activity of human hepatocellular carcinoma cells is associated
      with an overexpression of thyroid hormone beta 1 nuclear receptor and low
      expression of the anti-metastatic nm23 gene.
AB  - To understand the role of thyroid hormone in metastasis, we studied the
      expression of the anti-metastatic nm23 gene in eight human hepatocellular
      carcinoma (HCC) cell lines. These cells differentially expressed the anti
      metastatic nm23 gene. A low level of nm23 proteins was found to have a high in
      vitro invasive activity which correlated closely with an overexpression of the
      thyroid hormone beta 1 nuclear receptor (h-TR beta 1). Concurrent with the down
      regulation of h-TR beta 1, the invasive activity of HCC cells was suppressed by
      the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3). These results indicate that
      the invasive activity of HCC cells was regulated by T3, suggesting that T3 could
      be involved in modulating the functions of nm23.

PMID- 8529212
TI  - Adenoviral-mediated gene transfer into primary human and mouse mammary epithelial
      cells in vitro and in vivo.
AB  - Primary mammary epithelial cells from both the human and mouse mammary glands can
      be genetically altered under a variety of situations using the replication
      defective adenoviral vector containing a marker gene encoding the E. coli beta
      galactosidase. Primary human and mouse mammary epithelial cells in monolayer
      culture and in three-dimensional collagen gel culture systems were transduced by
      adenovector at high efficiency. Successful gene transfer was also accomplished in
      situ and in vivo. In the mouse mammary gland, anatomically restricted gene
      transfer and expression was demonstrated by micro-injection of adenoviral vector
      directly into the main duct of the mammary gland. Injection of adenoviral vector
      directly into the human mammary tissues from reduction mammoplasty specimens,
      into the mouse mammary gland-free fat pad containing the previously transplanted
      dissociated human mammary epithelial cells, and intratumorally into the human
      breast cancer xenografts in nude mice, all resulted in successful gene transfer
      to human mammary epithelial cells. High efficiency introduction of genetic
      material into primary mammary epithelial cells is important in the study of
      mammary carcinogenesis and potentially for gene therapy of human breast cancer.

PMID- 8529213
TI  - The in vivo anti-tumor activity of immunotoxins containing two versus one
      deglycosylated ricin A chains.
AB  - We have compared the in vitro and in vivo activities of three deglycosylated
      ricin A chain (dgA)-containing immunotoxins (ITs) with one versus two molecules
      of dgA per molecule of IgG. Two of the ITs (anti-CD19-dgA2 and anti-CD25-dgA2)
      had 3-0-fold improvements over their dgA1 counterparts in vitro. However, the in
      vivo anti-tumor activity of both constructs of each IT was the same. In contrast,
      anti-CD22-dgA2 was 7-fold more potent in vitro and significantly more potent in
      vivo than its dgA1 counterpart. These studies suggest that monoclonal antibodies
      must be individually tested to determine whether the addition of two versus one
      dgA will improve cytotoxic activity in vivo.

PMID- 8529215
TI  - Neuropaediatrics.

PMID- 8529216
TI  - Neuronal overmaturation in dysraphism: ontogenic expression of neuropeptides in
      the fetal brain and developmental anomalies in exencephaly.
AB  - Starting from knowledge obtained in our previous studies of experimental
      dysraphism in chick embryos, the entity of neuronal overgrowth observed in
      exencephaly was further investigated. The ontogenic expression of neuron-specific
      enolase (NSE), vasoactive intestinal polypeptide (VIP), and somatostatin was
      analyzed both in chick exencephaly of the natural product and in normal chick
      fetuses by carrying out immunohistochemical studies. In normal fetuses,
      immunostained elements positive for NSE first appeared in the spinal gray matter
      on postincubation day 16 and increased in intensity during the fetal period. By
      postnatal day 2, the cerebral peduncle, brain stem neurofibers, molecular layer
      of the cerebellum, corpus striatum, and piriform cortex became immunoreactive. No
      immunohistochemical reaction to VIP was observed during these stages.
      Somatostatin-positive elements were not identified during the fetal period,
      except in limited regions, such as the corpus striatum, which appeared to have
      weakly positive staining on day 21. The exencephalic fetuses, however,
      demonstrated extremely advanced neuronal maturation, with intense
      immunoreactivity already being manifest in various regions, including the corpus
      striatum, piriform cortex, spinal gray matter, and brain stem nuclei, on day 16
      of the fetal period. Somatostatin-positive elements also appeared at this stage
      in chick exencephaly, but such immunoreactivity was localized, particularly in
      the overgrown foci. The present study showed that the neuronal maturation process
      in some neurons of exencephalic brain and spinal cord was definitely further
      advanced than that in normal controls. A possible clinical application of NSE and
      somatostatin measurement as markers for dysraphic states in the fetus is
      suggested.

PMID- 8529217
TI  - Morphological modifications of the choroid plexus in a rodent model of acute
      ventriculitis induced by gram-negative liquoral sepsis. Possible implications in
      the pathophysiology of hypersecretory hydrocephalus.
AB  - Gram-negative bacterial infections of the central nervous system are generally
      associated with high morbidity and mortality rates. In patients with
      ventriculitis induced by gram-negative liquoral sepsis, a reduction in
      cerebrospinal fluid formation has been reported, suggesting that gram-negative
      ventriculitis is able per se to alter the normal functioning of the choroid
      plexus. The aim of the present study was to analyse, for the first time in the
      rat, the effects of acute ventriculitis on the ultrastructure of the choroid
      plexus. A simple and inexpensive experimental model of acute ventriculitis was
      developed: we injected into the cisterna magna of rats 10(3) CFU of live
      Escherichia coli, inducing septic ventriculitis without major neurological
      deficits. Histological examinations of rodent choroid plexus 24 h after the
      injection revealed patches of altered epithelium, with swollen and vacuolated
      ependymal cells associated with leukocyte infiltration. Electron microscopy
      demonstrated a reduced number of microvilli and flattening of the epithelial
      surface. These results (a) indicate that gram-negative septic ventriculitis is
      able to induce visible ultrastructural alterations of the choroid plexus which
      (b) are consistent with a picture of marked reduction of the functioning
      epithelial choroid plexus surface, and (c) highlight the potential usefulness of
      our rodent acute ventriculitis model for developing treatment modalities.

PMID- 8529218
TI  - Mutations and immunohistochemistry of p53 and proliferation markers in astrocytic
      tumors of childhood.
AB  - Thirty cases of hemispheric astrocytic tumors of childhood, consisting of 11
      pilocytic astrocytomas, 2 fibrillary astrocytomas, 9 anaplastic astrocytomas, and
      8 glioblastomas, were studied for the presence of p53 mutations and for
      immunohistochemical demonstrations of p53 and proliferation markers PCNA and Ki
      67 MIB-1. The study was performed using polymerase chain reaction (PCR)-assisted
      single-strand conformation polymorphism analysis of exons 5-8 and direct sequence
      analysis of PCR products. For immunohistochemistry, DO1 and PAb 1801 were used.
      No mutation and no positivity for p53 protein were found in pilocytic
      astrocytomas. Mutations (at codons 144, 202, and 245) were found in 2 out of 8
      glioblastomas and in 1 out of 9 anaplastic astrocytomas, whereas positive
      staining was found in 11 out of 17 malignant gliomas. Cases with mutations showed
      the highest p53 labeling index and also PCNA and MIB-1 labeling indices. The
      negative results in pilocytic astrocytomas are in line with the benign course of
      these tumors, whereas for malignant gliomas no difference seems to exist in
      comparison with adult cases.

PMID- 8529219
TI  - Current concept of hydrocephalus: evolution of new classifications.
AB  - Since hydrocephalus is a multifactorial disease with a diverse pathogenesis, no
      single, truly ideal classification of its exists. Hydrocephalus has been
      classified from various standpoints, each classification reflecting the current
      level of knowledge about hydrocephalus. Hydrocephalus needs to be classified
      according to the purpose of the study. There are two major categories of
      classification of hydrocephalus: academic and practical. Untreatable
      hydrocephalus still occurs. We propose a practical clinical classification based
      on the time of onset and the etiology for use in the clinico-epidemiologic study
      of intractable hydrocephalus and its future management.

PMID- 8529220
TI  - Horner's syndrome due to jugular venous ectasia.
AB  - Horner's syndrome may be caused by a lesion anywhere along the three-neuron
      pathway from the hypothalamus to the eye. This syndrome has been reported
      secondary to numerous causes to date. In this paper, we describe an extremely
      rare case of Horner's syndrome due to jugular venous extasia demonstrated by
      computed tomography and intravenous digital subtraction angiography.

PMID- 8529221
TI  - Intradural neurenteric cyst at the craniovertebral junction.
AB  - A case of an intraspinal neurenteric cyst at the craniovertebral junction in a 7
      year-old girl is reported. The intermittent progression of her neurological
      symptoms delayed the diagnosis. The location and cystic nature of the lesion were
      diagnosed with magnetic resonance imaging. Total surgical excision of the cyst
      was possible.

PMID- 8529222
TI  - Synthesis of pentasaccharide analogues of the N-glycan substrates of N
      acetylglucosaminyltransferases III, IV and V using tetrasaccharide precursors and
      recombinant beta-(1-->2)-N-acetylglucosaminyltransferase II.
AB  - Recombinant human UDP-GlcNAc: alpha-Man-(1-->6)R beta-(1-->2)-N
      acetylglucosaminyltransferase II (EC 2.4.1.143, GlcNAc-T II) was produced in the
      Sf9 insect cell/baculovirus expression system as a fusion protein with a (His)6
      tag and partially purified by affinity chromatography on a metal chelating
      column. The partially purified enzyme was used to catalyze the transfer of GlcNAc
      from UDP-GlcNAc to R-alpha-Man(1-->6)(beta-GlcNAc(1-->2)alpha-Man(1-->3))beta-Man
      O-octyl to form beta-GlcNAc(1-->2)R-alpha-Man(1-->6)(beta-GlcNAc(1-->2)alpha-
      Man(1-->3))beta-Man-O-octyl where there is either no modification of the alpha
      Man(1-->6) residue (7), or where R is 3-deoxy (8), 4-deoxy (9) or 6-deoxy (10).
      The yields ranged from 64-80%. Products were characterized by 1H and 13C nuclear
      magnetic resonance spectroscopy and fast atom bombardment mass spectrometry.
      Compounds 7-10 are pentasaccharide analogues of the biantennary N-glycan
      substrates of N-acetylglucosaminyltransferases III, IV and V.

PMID- 8529223
TI  - Synthetic mucin fragments: synthesis of O-sulfo and O-methyl derivatives of allyl
      O-(beta-D-galactopyranosyl)-(1-->3)-2-acetamido-2-deoxy-alpha-D-
      galactopyranoside as potential compounds for sulfotransferases.
AB  - Allyl 2-acetamido-4,6-O-(4-methoxybenzylidene)-2-deoxy-alpha-D-galact opy
      ranoside (1) was condensed with either 2,3,4,6-tetra-O-acetyl-alpha-D
      galactopyranosyl bromide (2) or 2,3,4-tri-O-benzoyl-6-O-bromoacetyl-alpha-D
      galactopyranosyl bromide (14) in the presence of mercuric cyanide. Selective
      substitution with methyl, sulfo or both at desired positions, followed by the
      removal of protecting groups, afforded allyl O-(beta-D-galactopyranosyl)-(1-->3)
      2-acetamido-2-deoxy-6-O-methyl-alpha -D- galactopyranoside (5), allyl O-(6-O
      sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy-6- O
      methyl-alpha-D-galactopyranoside (10), allyl O-(beta-D-galactopyranosyl)-(1-->3)
      2-acetamido-2-deoxy-6-O-sulfo-alpha- D- galactopyranoside sodium salt (13), allyl
      O-(6-O-sulfo-beta-D-galactopyranosyl sodium salt)-(1-->3)-2-acetamido-2-deoxy-
      alpha-D-galactopyranoside (17) and allyl O-(3-O-sulfo-beta-D-galactopyranosyl
      sodium salt)-(1-->3)-2-acetamido-2-deoxy- alpha-D-galactopyranoside (22). The
      structures of compounds 5, 10, 13, 17 and 22 were established by 13C NMR and FAB
      mass spectroscopy.

PMID- 8529224
TI  - Structural analysis of the O-antigen of the lipopolysaccharide of Rhizobium
      tropici CIAT899.
AB  - The structure of the O-antigen chain of the lipopolysaccharide isolated from
      Rhizobium tropici CIAT899, by the phenol-water procedure, and recovered from the
      phenol layer, has been investigated by hydrolysis, methylation analysis and 1D
      and 2D 1H and 13C NMR spectroscopy of the complete polysaccharide and of
      oligosaccharides obtained by partial hydrolysis. The O-antigen has the repeating
      unit [formula: see text]

PMID- 8529226
TI  - Structure of an exocellular polysaccharide of Lactobacillus helveticus TN-4, a
      spontaneous mutant strain of Lactobacillus helveticus TY1-2.
AB  - Lactobacillus helveticus strain TN-4, a spontaneous mutant strain of
      Lactobacillus helveticus TY1-2, produced an exocellular polysaccharide from
      reconstituted skim milk. On the basis of the results of methylation analysis,
      enzymatic digestion, mild Smith degradation, mild acid hydrolysis, acetolysis,
      and 1D and 2D 1H-NMR spectroscopy, it was concluded that the polysaccharide has a
      D-galactofuranose containing hexasaccharide repeating unit with the following
      structure: [formula see text]

PMID- 8529225
TI  - Characterization of a monoclonal antibody that recognizes an arabinosylated (1-
      >6)-beta-D-galactan epitope in plant complex carbohydrates.
AB  - Monoclonal antibody CCRC-M7 is representative of a group of antibodies with
      similar binding specificity that were generated using the plant cell-wall pectic
      polysaccharide, rhamnogalacturonan I, as immunogen. The epitope recognized by
      CCRC-M7 is present in several plant polysaccharides and membrane glycoproteins.
      Selective enzymatic or chemical removal of arabinosyl residues from
      rhamnogalacturonan I reduced, but did not abolish, the ability of CCRC-M7 to bind
      to the polysaccharide. In contrast, enzymatic removal of both arabinosyl and
      galactosyl residues from rhamnogalacturonan I completely abolished binding of
      CCRC-M7 to the resulting polysaccharide. Competitive ELISAs using chemically
      defined oligosaccharides to compete for the CCRC-M7 binding site showed that
      oligosaccharides containing (1-->6)-linked beta-D-galactosyl residues were the
      best competitors among those tested, with the tri-, penta-, and hexa-saccharides
      being equally effective. The combined results from indirect and competitive
      ELISAs suggest that the minimal epitope recognized by CCRC-M7 encompasses a (1-
      >6)-linked beta-galactan containing at least three galactosyl residues with at
      least one arabinosyl residue attached.

PMID- 8529227
TI  - Structural elucidation of the capsular polysaccharide of Bacteroides fragilis
      strain 23745M1.
AB  - The capsule of Bacteroides fragilis (ATCC23745) consists of two distinct
      polysaccharides, the separation of which could not be accomplished. The mouse
      passaged strain (23745M1), however, yielded a preponderant polysaccharide which
      was isolated and purified. Using mainly high resolution NMR spectroscopy, the
      structure of the polysaccharide was elucidated and it is composed of the
      following repeating unit: [formula see text]

PMID- 8529228
TI  - Different populations of pectic hairy regions occur in apple cell walls.
AB  - Alcohol insoluble solids from apple were extracted in sequence by buffer at 20
      degrees C and at 70 degrees C, EDTA/oxalate, and mild alkali, yielding four
      populations of pectins. These pectins and the insoluble residue were
      characterized by their sugar composition, degree of esterification (methyl ester
      and O-acetyl groups), molecular weight distribution, and degradability by the
      combination of endopolygalacturonase (PG) and pectin esterase (PE) and by
      rhamnogalacturonase (RGase) after chemical saponification. After PG/PE treatment,
      the remaining high molecular weight material representing the pectic hairy
      regions was isolated and characterized. Clear differences were found in the sugar
      composition of the fractions obtained, while only small variations were observed
      in the sugar linkage composition. The pectic hairy regions were further degraded
      by RGase and the digests separated into high molecular weight and oligomeric
      degradation products. These "RGase oligomers" consisted of between 4 and 9 sugar
      units with a backbone of alternating rhamnose and galacturonic acid residues,
      partly substituted with galactose linked to C-4 of the rhamnose moiety. Both the
      absolute amount of RGase oligosaccharides released as well as the degree of
      galactose-substitution of the oligomers increased when severer extraction
      conditions were used. Relatively more RGase oligomers were released from the low
      molecular weight hairy regions as compared to the high molecular weight fraction.
      Typical high molecular weight fragments isolated from the RGase digests of
      various hairy regions included residual segments of the rhamnogalacturonan
      backbone rich in arabinose and a polymer presumably enriched in xylogalacturonan
      segments.

PMID- 8529229
TI  - The structure of the acidic exopolysaccharide produced by Pseudomonas "gingeri"
      strain Pf9.
AB  - The structure of the acidic exopolysaccharide produced by the mushroom pathogen
      Pseudomonas "gingeri" strain Pf9, a bacterium which causes ginger blotch, was
      investigated by chemical analysis, mass spectrometry and 1D and 2D NMR
      spectroscopy. The polysaccharide consists of the linear trisaccharide repeating
      unit [formula: see text] where the cyclic pyruvic acetal groups at O-4 and O-6 of
      the mannopyranosyl residues have the S-configuration. Methylation analysis under
      neutral conditions and NMR data showed that the mannose residues are acetylated
      at O-2. This exopolysaccharide has the same structure as the E. coli K55 capsular
      polysaccharide and differs from the Klebsiella K5 capsular polysaccharide only in
      the position of acetylation (C-2 of the glucopyranose residue).

PMID- 8529230
TI  - Gradient-enhanced homonuclear 2D NMR techniques applied to oligosaccharides
      containing manno-hexoses provide improved correlations for protons coupled by
      small 3J.

PMID- 8529231
TI  - Conformational analysis of sucrose octasulfate by high resolution nuclear
      magnetic resonance spectroscopy.

PMID- 8529233
TI  - Synthesis and unusual glycosidic coupling reaction of substituted 2,7
      dioxabicyclo[4.1.0]heptanes: 1,2-anhydro-3,4-di-O-benzyl-alpha-D-fucopyranose.

PMID- 8529232
TI  - [Synthesis of modified tetrasaccharides as analog acceptor-inhibitors of N
      acetylglucosaminyltransferase II].

PMID- 8529234
TI  - [Inhibition of the neurohumoral axis after intravascular fluid depletion in
      congestive heart failure with water retention: mechanisms of the perpetuation of
      the syndrome].
AB  - Hypovolemia stimulates the sympathoadrenal and renin systems and water retention.
      In congestive heart failure (CHF) reduced cardiac output and blood pressure have
      been suggested to be perceived as a volume deficit, which, if persistent, would
      perpetuate humoral activation and fluid retention. In the aim of probing this
      hypothesis, we monitored in patients with CHF the neurohumoral response to
      reduction of the body fluid obtained by ultrafiltration. In 22 patients with
      advanced CHF and fluid retention, ultrafiltration was performed with a diafilter,
      which was part of an external venous circuit, whose flow was regulated to produce
      500 ml/hour of ultrafiltrate (average total amount 3,122 +/- 1,199 ml) until
      right atrial pressure was reduced to 50% of baseline. Hemodynamics, plasma renin
      activity, norepinephrine and aldosterone were measured before and in the 48 hours
      after ultrafiltration. Soon after the procedure, associated with a 20% reduction
      of plasma volume and a moderate decrease of cardiac output and blood pressure
      (consistent with a diminished degree of filling of the arterial compartment),
      there was an obvious fall of norepinephrine, plasma renin activity and
      aldosterone. In the next 48 hours we recorded an increasing neurohumoral axis
      depression, in spite of recovery of plasma volume, cardiac output and blood
      pressure and a striking enhancement in urinary output. Changes in norepinephrine,
      plasma renin activity or aldosterone were not related to the combination of
      changes in plasma volume, cardiac output and blood pressure (variations in the
      state of arterial filling) and significantly correlated with the increase in
      urinary output and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529236
TI  - [Clinical value of intracavitary electrograms stored by implantable automatic
      defibrillator in patients resuscitated after cardiac arrest].
AB  - A major limitation of implantable defibrillators in the past has been the
      inability to document the arrhythmia precipitating discharge of the device.
      Although symptoms can be of some help in identifying the arrhythmia, symptomatic
      supraventricular arrhythmias and asymptomatic ventricular tachycardia (VT) have
      been documented in some cases before device discharge. The aim of this study was
      to systematically assess the value of stored intracardiac electrograms by
      implantable cardioverter-defibrillator in survivors of cardiac arrest during an
      antiarrhythmic drug free-period, in order to better define the arrhythmic profile
      determining device activation. The stored intracardiac electrograms of a fourth
      generation cardioverter-defibrillator, implanted in 18 survivors of cardiac
      arrest were retrieved. The number of device activations, and the characteristics
      of any stored arrhythmic events were analyzed. A total number of 249 arrhythmic
      events were detected and stored over a mean follow-up of 378 +/- 107 days. These
      resulted in 78 delivered shocks, 84% of which were appropriate. Most of the
      detected events were episodes of unsustained VTs (33%), and atrial fibrillation
      or flutter (31%), which led to inappropriate shocks in 16% of the cases. The
      remaining recorded events were: sustained VT or fibrillation (66 episodes, 26%),
      sinus rhythm (11 events, 4%), not classified episode (6%). Of the 171 (69%)
      arrhythmic episodes not resulting in shocks, 73 events aborted before shock
      delivery by the device's reconfirmation algorithm, and the remaining 98 (39%)
      were detected but unsustained in duration, thus terminating before charging. In
      some cases, sustained and unsustained episodes of both supraventricular and
      ventricular arrhythmias gave symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529235
TI  - [Idiopathic atrial fibrillation: clinical-instrumental characterization and
      thromboembolic risk].
AB  - Ninety-two patients with diagnosis of lone atrial fibrillation (AF) were
      retrospectively identified by our in-hospital records. Among the 92 patients, 62
      were males and 30 females. Mean age was 50 +/- 15 years (range 13-81). In 30% of
      the patients mild to moderate systemic hypertension was present. None had thyroid
      dysfunction. At the time of our first clinical observation, AF showed the
      following characteristics: recurrent AF in 58% of the cases (53 patients),
      chronic AF in 16% of the cases (15 patients) and first episode of AF in 26% of
      the cases (24 patients). Patient's symptoms were: palpitation in 73% of the
      cases, dyspnea in 24%, asthenia in 22%, chest pain in 19%, dizziness in 19% and
      syncope in 9% of the cases. In 9% of the subjects AF was asymptomatic. Recurrent
      AF presented with more than one episode per day in 12% of the cases, one per week
      in 16% of the cases, one-two episodes in 1 month in 8% of the cases and between
      two and six episodes in 1 year in 33% of the cases. Cross-sectional
      echocardiography, evidenced a higher prevalence of left atrial enlargement in
      patients with chronic AF (7/15 cases = 47%) either compared to subjects with
      recurrent AF (5/53 cases = 9%, p < 0.005) or compared to subjects with a first
      episode of AF (3/24 cases = 11%, p < 0.05). Echocardiographic signs of left
      ventricular dysfunction (left ventricular enlargement or hypokinesia) were found
      in 27% of the patients with chronic AF and in 8% of the other two groups
      (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529237
TI  - [Role of low-frequency neuronal activity in the medulla in the regulation of the
      cardiovascular system].
AB  - We recorded discharge activity of 45 single neurons located in the rostral
      ventrolateral medulla (n = 21), lateral tegmental field (n = 10) and caudal raphe
      (n = 14) nuclei in baroreceptor-denervated decerebrate cats (n = 27).
      Autoregressive spectral analysis was performed on neuronal activity and systolic
      arterial pressure (SAP). The discharges of the recorded neurons were correlated
      to 2- to 6 Hz oscillations or 10 Hz rhythm present in sympathetic neural
      discharge. A low frequency (LF) oscillation (0.12 +/- 0.02 Hz) was observed in 25
      (55%) units. The same rhythmicity was found in SAP variability in 25 of 45 (55%)
      recordings. In 21 of these cases the LF in SAP variability was highly correlated
      to LF in neural activity. Moreover, 32 out of 45 (71%) neurons showed a higher
      rhythm (HF; 0.34 +/- 0.06 Hz) related to the ventilation rate. These data
      demonstrate the presence of an LF oscillation in the discharge of single
      medullary neurons, involved in the regulation of cardiovascular system. This LF
      component was similar to that detectable in the spectral analysis of SAP
      variability, thus supporting the hypothesis of a central origin of this rhythm,
      largely independent of baroreceptor input.

PMID- 8529239
TI  - [Electrocardiography: membrane potentials according to the chaos theory].

PMID- 8529238
TI  - [Reduced endothelium-dependent peripheral vasodilation in the aged].
AB  - Endothelial dysfunction may be present years before the clinical manifestations
      of atherosclerosis, which is particularly frequent in the late decades of life.
      Therefore, we have evaluated the presence of endothelial dysfunction in the
      elderly by measuring, by echo-Doppler technique, the vasodilatation of brachial
      artery in response to the hyperemia following forearm occlusion and
      decompression, a response that is dependent on endothelial function. We studied
      10 subjects > 65 years (mean 72 +/- 8) and 10 subjects < 65 years (mean 40 +/- 6)
      all without clinical signs and without risk factors for atherosclerosis. The
      increase in brachial arterial flow during reactive hyperemia was similar in the
      young and elderly subjects (152 +/- 74% vs 129 +/- 63%, NS). While in the young
      at peak hyperemia we found a significant increase in brachial artery diameter
      from 3.4 +/- 0.9 to 4.1 +/- 1.0 mm (p < 0.005), there was no significant change
      in the elderly (from 3.0 +/- 0.7 to 3.1 +/- 0.7 mm, NS). In both groups
      sublingual glyceryl trinitrate produced a significant increase in brachial artery
      diameter (from 3.0 +/- 0.7 to 3.5 +/- 0.8 mm in the elderly, p < 0.01, and from
      3.4 +/- 0.9 to 3.9 +/- 0.9 mm in the young subjects, p < 0.01, NS among groups),
      showing the absence in the elderly of structural vascular changes potentially
      responsible for absence of dilatation. In conclusion, elderly subjects without
      clinical signs or risk factors for atherosclerosis have a vascular endothelial
      dysfunction that may play an important role in pathologic processes of the
      cardiovascular system in the late decades of life.

PMID- 8529240
TI  - [Preconditioning of the ischemic myocardium].

PMID- 8529241
TI  - [New trends in the evaluation of myocardial viability by echocardiography].

PMID- 8529242
TI  - [Clinical and echocardiographic evaluation of thalassemic cardiomyopathy].
AB  - To evaluate the reliability of the echocardiographic examination in assessment of
      adult patient with thalassemia major, in comparison with clinical,
      electrocardiographic and/or chest x ray exams, 103 patients with thalassemia
      major, mean age 20 years (range 14 to 30 years), were studied and compared with
      30 age matched normal subjects. All patients were receiving transfusions
      regularly to maintain hemoglobin levels above 11 g/dl and subcutaneous infusions
      of desferrioxamine (about 40 mg/kg/day) to reduce hemosiderosis. The patients
      were divided into three groups according to their cardiac impairment, deduced by
      clinical history, electrocardiography (ECG) and/or chest x ray. Group I (36
      patients) showed no signs or symptoms of cardiac impairment. Group II (38
      patients) had only signs of cardiac impairment by ECG and/or chest x ray. Group
      III (29 patients) had both symptoms and signs of cardiac failure. In comparison
      to normal controls, Group I showed an increase in left ventricular (LV) dimension
      (EDD) and mass (p < 0.001), Group II and III showed a decrease in LV fractional
      shortening (FS; p < 0.001) too. In comparison to Group I, Group II showed a
      decrease in LV FS (p < 0.05), Group III showed an increase in LV EDD and mass (p
      < 0.001) too. In comparison to Group II, Group III showed an increase in LV EDD
      and mass (p < 0.001), and a decrease in LV FS (p < 0.001). In conclusion,
      echocardiographic examination appears a tool more reliable than clinical,
      electrocardiographic and/or chest x ray examination in assessment of adult
      patient with thalassemia major.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529243
TI  - [Ambulatory monitoring of blood pressure profiles in in hypertensive patients 26
      65 years of age].
AB  - We evaluated blood pressure profile in a population of 380 untreated
      hypertensives (210 males, 170 females, stage 1 and 2 JNC 1993) observed
      consecutively. A 24-hour ambulatory blood pressure monitoring was performed using
      and A&D TM 2420 model 6 device programmed to measure systolic and diastolic blood
      pressure every 15 min from 7 am to 10 pm (daytime) and every 30 min from 10 pm to
      7 am (night-time). Statistical analysis was carried out by dividing the patients
      into four groups on the basis of age: Group I, from 26 to 35 years (26 males, 14
      females); Group II, from 36 to 45 years (48 males, 39 females); Group III, from
      46 to 55 years (85 males, 72 females); Group IV, from 56 to 65 years (51 males,
      45 females). Systolic blood pressure was higher in older male hypertensives (56
      to 65 years) who also had a persistent systolic blood pressure elevation during
      night-time (non-dippers); diastolic blood pressure was significantly higher in
      male hypertensives aged 36 to 55 years.

PMID- 8529244
TI  - [Diagnostic accuracy of transesophageal echocardiography in the diagnosis of
      aortic dissection: comparison with computerized axial tomography].
AB  - This study was designed to assess the sensibility, specificity and diagnostic
      accuracy of transesophageal echocardiography (TEE) and X-ray contrast enhanced
      computed tomography (CT) in the diagnosis of aortic dissection and its
      complications. Fifty patients with clinically suspected aortic dissection were
      examined. Imaging results were validated in each case by intraoperative and/or
      autopsy findings and/or the results of cineangiography. The Stanford and DeBakey
      classifications were used to differentiate the dissection type; the patients were
      also subdivided by TEE according to a modified DeBakey classification. The
      sensibility of TEE to detect aortic dissection was 100%, significantly higher (p
      < 0.05) than that of CT for type A dissections (77.2%). The two imaging
      procedures did not statistically differ (NS) in the detection of type B
      dissection (CT sensibility 87.5%). The specificity of TEE for the detection of
      type A aortic dissection was 94%; it was not significantly higher (NS) than that
      of CT (CT specificity 86.6%). Both TEE and CT had no false negative findings in
      the diagnosis of type B aortic dissection (100%; TEE vs CT, NS). TEE was reliable
      in the correct identification of the primary entry site in the ascending aorta
      (80%), the arch (62.5%) and descending aorta (71.4%), and also in the involvement
      of coronary arteries (62.5%), and aortic arch branch vessels (71.4%); CT scanning
      was not effective in detecting any of these complications. Aortic regurgitation
      was accurately identified by TEE in each case. Both TEE and CT scanning correctly
      identified thrombosis of the false lumen and pericardial effusion. Intraoperative
      TEE documented in all patients postrepair persistence of the intimal flap in
      aortic segments that were not operated; flow in the false lumen was detected in
      46.6% of the patients; in 26.6% of them secondary tears, not seen before surgical
      treatment, were detected. In conclusion, TEE allows a bedside, safe and accurate
      diagnosis and classification of aortic dissection. It also provides the
      diagnostic information necessary for the therapeutical decision making.
      Intraoperative TEE allows improvement in preoperatory diagnosis and gives
      important information for the management of the patient immediately after
      cardiopulmonary bypass and in the follow-up.

PMID- 8529246
TI  - [Secondary prevention of ischemic cardiopathy].

PMID- 8529245
TI  - [Atrial ejection force. Findings in healthy subjects].
AB  - Atrial ejection force was measured by Doppler echocardiography from the A-wave of
      the transmitral inflow pattern. Atrial ejection force was measured in 72 normal
      subjects, 36 males and 36 females aged 20 to 80 years, 12 patients for each
      decade. Using bivariate correlation we analyzed the relationship between atrial
      ejection force and biological parameters: age, height, weight, body surface;
      clinical parameters: heart rate, systolic, diastolic and mean blood pressure;
      echocardiographic measures: left atrial dimensions. A significant correlation
      between atrial ejection force and age (r = 0.9, p < 0.001) was found. The atrial
      ejection force was also correlated with left atrial dimensions (p < 0.01). No
      relations between atrial ejection force and other clinical parameters were found.
      The atrial ejection force is a potentially useful parameter for assessing the
      atrial contribution to diastolic performance, the age-corrected normogram is
      essential when assessing atrial ejection force in individual patients.

PMID- 8529247
TI  - [Dispersion of ventricular recovery time as a new marker of arrhythmogenic risk].

PMID- 8529248
TI  - [Multiple spontaneous coronary dissection. Case report and review of the
      literature].
AB  - We refer a case of a 57-year-old woman with an acute myocardial infarction of the
      anterior wall, treated with rt-PA, aspirin and heparin. In the following days, in
      spite of the therapy, occurred a second acute myocardial infarction of the
      inferior wall complicated with ventricular fibrillation. Coronary angiography
      showed multiple coronary dissection involving the left anterior descending and
      the circumflex coronary arteries. The characteristic feature of this case
      consists of the multiple coronary dissection responsible for myocardial
      infarctions, an event seldom reported in the literature.

PMID- 8529249
TI  - [Provocation tests in echocardiography: stress--dipyridamole--dobutamine].

PMID- 8529250
TI  - [Aneurysmatic pathology of the thoracic aorta].

PMID- 8529251
TI  - Drug treatment of hypertension in the elderly.

PMID- 8529252
TI  - Exposure to moderate altitude and cardiorespiratory diseases.

PMID- 8529253
TI  - [The observation by echocardiographic monitoring of the behavior of the main
      morphofunctional parameters of the left ventricle after an acute myocardial
      infarct].
AB  - In acute myocardial infarction (AMI) echocardiography is a means for revealing
      anatomical and functional damage. Up to date utilization of this method to
      monitor cardiac function during the in-hospital phase of AMI is rarely adopted.
      We performed serial echocardiographic examinations during the in-hospital phase
      of AMI to study the behaviour of left ventricular function at day 1, day 4-6 and
      at pre-discharge (after 11 +/- 3 days from admission). End diastolic volume
      (EDV), end systolic volume (ESV), ejection fraction (EF), wall motion score index
      (WMSI) were assessed. The study involved 108 patients with first AMI and with
      adequate echocardiographic resolution, selected from a population of 194 subjects
      consecutively admitted to the coronary care unit for suspected AMI. The
      population features were: mean age 60 +/- 13 years, 89 males and 19 females, 61
      with anterior AMI and 47 with inferior AMI, 77 treated and 31 not treated by
      thrombolysis. Echocardiography was performed on day 1 (always after thrombolysis
      in treated patients), day 4-6, and at pre-discharge (11 +/- 3 days after
      admission) EDV, ESV and EF were calculated by single plane area-length method
      from the apical 4-chamber view; WMSI was calculated on a left ventricular 16
      segment model, using the following scale: 1: normal or hyperkinetic; 2:
      hypokinetic; 3: akinetic, 4: dyskinetic, 5: aneurysm, and dividing the sum by the
      number of visualized segments. A modification in EDV and ESV was considered if
      there was a +/- 10% change in comparison with the initial or previous
      examination; EF was also considered to be modified for changes +/- 10%; WMSI was
      considered to be improved or worsened either in case of score variations of
      previously altered segments or in case of detection of new abnormally contracting
      segments. In order to improve reproducibility and adequate comparison of serial
      measurements we used a cine-loop technology with dual or quad-screen imaging.
      EDV, ESV EF and WMSI presented heterogeneous variations from day 1 to pre
      discharge. For each observed parameter, we identified three main groups and six
      subgroups. Main groups identify stability (Group I), improvement (Group II) and
      worsening (Group III); subgroups, concerning only Group II and III and named a, b
      and c, identify the characteristics of improvement or worsening: a: continuous or
      persistent, b: late and c: discontinuous. No significant differences were found
      in each parameter between thrombolysed and non thrombolysed patients. As to the
      concomitance of belonging to the same main group, EF and WMSI presented the
      greatest agreement: 76% of patients; ESV, EF and WMSI agreed in 71% of patients;
      EDV, ESV, EF and WMSI agreed only in 59% of patients.

PMID- 8529254
TI  - [The SINTESI Project: software in cardiovascular prevention].
AB  - Coronary heart disease is the most important cause of mortality in adults. New
      approaches may reduce the cardiovascular risk in population. "SINTESI" is an
      original data base designed in collaboration with the Italian Group for the Study
      of Metabolism Disease and Atherosclerosis to improve the evaluation of the major
      risk factors in the population and to create a data bank for medical research. It
      runs in Windows. The software includes the following electronics archives:
      Demographics; History; Follow-up; ECG; Laboratory; Doppler-echocardiography;
      Stress test-ECT; Ambulatory blood pressure monitoring; Holter-ECG; Nuclear
      imaging; Vascular echo-Doppler; Hemodynamics; Radiology. We named the most
      important file "Main Working Area" (MWA). This displays all the most important
      information on the clinical status of the patients and represents the "console"
      for using the software. In fact, in MWA "buttons" are displayed to enter all the
      electronic archives. The software displays graphics and the flow-chart of
      clinical history. We implemented "routines" for automatic evaluation of several
      variables. We also simplify the statistical use of the data implementing
      functions for "query" that permit the management of data bank. The use of this
      software may facilitate the correct evaluation and stratification of the
      cardiovascular risk. In conclusion, "Progetto SINTESI" is an easy, synthetic
      organization of patient's clinical data and a complete data bank. It is our
      opinion that the use of this software may promote a standard way of collecting a
      large number of data to improve the stratification of cardiovascular risk.

PMID- 8529255
TI  - [Serum C3 as a screening factor in the primary prevention of myocardial infarct].
AB  - This study addresses the possible use of serum C3 (third component of the
      complement system) to select the subjects to be submitted to diet or drug therapy
      in the primary prevention of myocardial infarction. C3 is synthesized by
      macrophages, which are the main cells involved in atheroma formation, and an
      association between serum C3 and the risk of myocardial infarction has recently
      been found in the male sex. We have studied 332 men aged 45-75 years, who had no
      cardiovascular disease at any time before blood sampling. In their sera C3
      measurement was performed by nephelometry. The 4 year follow-up was known for all
      of these subjects: in particular, 11 had a myocardial infarction. The average LDL
      cholesterol (LDL-C) levels in the whole population were rather high (162.2 +/-
      45.8 (1 SD) mg/dl). As standard treatment criteria (A), those suggested for
      primary prevention by the National Cholesterol Education Program panel of experts
      were adopted: diet if LDL-C > or = 160 mg/dl, or LDL-C > or = 130 mg/dl + 2
      additional risk factors; drugs if, after diet, LDL-C > or = 190 mg/dl, or LDL-C >
      or = 160 mg/dl + 2 risk factors. This scheme was compared with two models of
      treatment which included the measurement of serum C3. According to the first of
      such models (B), diet should be prescribed when C3 levels are within the high
      third of distribution (> or = 135 mg/dl) with LDL-C > or = 100 mg/dl, and drugs
      should be given if, after diet, serum C3 is > or = 135 mg/dl with LDL-C > or =
      130 mg/dl. The second model based on C3 (C) is of combined type since, in
      addition to model B criteria, it also suggests to prescribe a diet if LDL-C > or
      = 190 mg/dl, while drugs should be given if, after diet, LDL-C levels persist >
      or = 190 mg/dl. The effect of diet has been simulated by assuming a 10% decrease
      in LDL-C levels. According to all of these criteria, the subjects to treat with
      diet with the models A, B and C would have been, respectively, 71, 27 (p < 0.0001
      vs mod A) and 45% (p < 0.0001 vs mod A) of the whole population, including among
      them, respectively, 82, 82 and 100% of the future myocardial infarctions. After
      diet, according to the three models A, B and C -29, 20 (p = 0.0117 vs mod A) and
      30% of the whole population should have been treated with drugs, including,
      respectively, 54, 64 and 82% of the future myocardial infarctions. In conclusion,
      the use of criteria based on serum C3, with respect to more traditional
      guidelines, might allow a more precise identification of the subjects to submit
      to diet and drug treatment in the primary prevention of myocardial infarction.

PMID- 8529256
TI  - [The finding of endocardial fibroelastosis in a 20-week-old fetus].
AB  - Endocardial fibroelastosis is a rare disease that only sporadically has been
      diagnosed prenatally. The cases reported so far were found after the second
      trimester of pregnancy. We report a case of endocardial fibroelastosis found in a
      20-week fetus, in whom the diagnosis was performed by echocardiography and, after
      voluntary interruption of pregnancy, was confirmed by necroscopy and histology.
      Early intrauterine detection of endocardial fibroelastosis allows to plan
      pregnancy, modality of delivery and a possible therapy.

PMID- 8529257
TI  - [Lung water].

PMID- 8529258
TI  - Abnormal calcium homeostasis in Duchenne muscular dystrophy myotubes contracting
      in vitro.
AB  - Resting intracellular calcium activity was recorded in three kinds of human
      muscle cells in culture: normal (control) and dystrophic (DMD and FSH), by means
      of a ratiometric fluorescence method using the calcium probe Indo-1 under laser
      illumination. DMD cells are characterized by a lack of dystrophin whereas FSH
      cells express normal dystrophin. The aim of this study was to determine whether,
      in dystrophin-deficient muscle cells (DMD), contraction destabilized internal
      calcium homeostasis. Muscle cells were cocultured with rat spinal cord explants
      to improve the maturation of human myotubes up to the stage where contraction
      appears. The resting intracellular calcium level was significantly higher in
      contracting DMD cells (107 +/- 8 nM; n = 44) compared to control cells (66 +/- 6
      nM; n = 43) or in FSH cells (56 +/- 6 nM; n = 35). DMD myotubes cocultured in the
      presence of TTX which inhibited contractile activity, did not develop an increase
      in free cytosolic Ca2+ concentration. The amplitudes of calcium transients
      elicited by exposure to acetylcholine (ACh) or high K+ medium (100K) were
      significantly higher in contracting DMD myotubes than in control ones. The extra
      responses were not observed in DMD myotubes cocultured with TTX. This study
      strongly suggest that: (i) contraction is a dominant factor contributing to Ca2+
      abnormalities in DMD cells; and (ii) contracting dystrophin-deficient cells have
      defective calcium handling mechanisms during electrical events which involve
      sarcolemma.

PMID- 8529259
TI  - Calbindin-D28K facilitates cytosolic calcium diffusion without interfering with
      calcium signaling.
AB  - The role of calbindin-D28K, in transcellular Ca2+ transport and Ca2+ signaling in
      rabbit cortical collecting system was investigated. Rabbit kidney connecting
      tubules and cortical collecting ducts, hereafter referred to as cortical
      collecting system, were isolated by immunodissection and cultured to confluence
      on permeable filters and glass coverslips. Calbindin-D28K was present in the
      cytosol of principal cells, but was absent from the intercalated cells.
      1,25(OH)2D3 (48 h, 10(-7) M) significantly increased cellular calbindin-D28K
      levels (194 +/- 15%) and stimulated transcellular Ca2+ transport (41 +/- 3%).
      This stimulatory effect could be fully mimicked by the endogenous Ca2+ chelator,
      BAPTA (30 microM BAPTA/AM), which suggests that the presence of Ca2+ chelators
      alone is sufficient to enhance transcellular Ca2+ transport. Stimulation of Ca2+
      transport was not accompanied by a rise in [Ca2+]i. Isosmotic replacement of
      extracellular Na+ ([Na+]o) for N-methylglucamine (NMG) generated oscillations in
      [Ca2+]i in individual cells of the monolayer. The functional parameters of these
      oscillations such as frequency of spiking, resting [Ca2+]i, increase in [Ca2+]i
      and percentage of responding cells, were not affected by the level of calbindin
      D28K. In contrast, loading the cells with BAPTA abruptly stopped these [Ca2+]i
      oscillations. This suggests that the kinetics of Ca2+ binding by calbindin-D28K
      are slow relative to the initiation of the [Ca2+]i rise, so that calbindin-D28K,
      unlike BAPTA, is unable to reduce [Ca2+]i rapidly enough to prevent the
      initiation of Ca(2+)-induced Ca2+ release.

PMID- 8529260
TI  - Phosphorylation with protein kinases modulates calcium loading of terminal
      cisternae of sarcoplasmic reticulum from skeletal muscle.
AB  - We previously found in single channel studies that ryanodine receptor (RyR)
      channel activity can be made insensitive to block by Mg2+ when terminal cisternae
      of sarcoplasmic reticulum, incorporated into planar bilayers, are treated with
      protein kinase A (PKA) or Ca2+/calmodulin dependent protein kinase type II (CamPK
      II), and then again made sensitive by treatment with protein phosphatases [Hain
      J. Nath S. Mayrleitner M. Fleischer S. Schindler H. (1994) Phosphorylation
      modulates the function of the calcium release channel of sarcoplasmic reticulum
      from skeletal muscle. Biophys. J., 67, 1823-1833]. In this study, modulation by
      protein kinases and phosphatases on net Ca2+ uptake by TC is presented.
      Phosphorylation of TC vesicles with PKA, CamPK II, or protein kinase C (PKC)
      reduced the calcium loading rate of TC vesicles 3-fold, 2.1-fold and 1.7-fold,
      respectively, measured in the presence of 1 mM MgCl2. There is no effect when AMP
      PNP is substituted for ATP. Phosphorylation of the RyR was also measured by
      incorporation of [gamma-32P]-phosphate from ATP. A phosphorylation stoichiometry
      of 1.94 +/- 0.1 (32P/RyR) for PKA, 0.89 +/- 0.08 for CamPK II and 0.95 +/- 0.16
      for PKC was obtained under these conditions. A study of the time dependence of
      phosphorylation with PKA and CamPK shows a direct correlation of reduction in
      calcium loading rate with increased phosphorylation of the ryanodine receptor.
      Treatment with protein phosphatase 1 enhanced the calcium loading rate again,
      after it was reduced by PKA phosphorylation. Investigation of the magnesium
      dependency shows that even at higher [Mg2+] (6 mM), PKA phosphorylated TC
      vesicles have a 2.3-fold reduced calcium loading rate indicating insensitivity to
      block by Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529261
TI  - Do nitric oxide and cGMP play a role in calcium cycling?
AB  - The biological molecule NO and its cyclic nucleotide effector molecule cGMP, are
      involved in a variety of biological systems. This article reviews evidence
      supporting a role for these molecules in signal transduction. Over the last 10
      years, it has become evident that these molecules are important in Ca2+
      regulation, particularly in excitable cells. In these cells, cGMP-dependent
      mechanisms appear to both directly and indirectly regulate Ca2+ transport. Until
      recently, reports of the actions of cGMP in non-excitable cells have been
      contradictory, presenting a confusing plethora of effects. In these cells, the
      cGMP-Ca2+ regulation pathway appears to be concentration-dependent, possibly
      representing a negative feedback mechanism. Ca2+ entry appears to be activated
      when low concentrations of cGMP are present, and inhibited at higher
      concentrations. The role of cGMP in Ca2+ regulation in non-excitable cells has
      been largely overlooked and further investigation of this issue may provide clues
      as to the nature of various unknown components that induce Ca2+ entry into these
      cells.

PMID- 8529262
TI  - Nickel: an agent for investigating the relation between hormone-induced Ca2+
      influx and bile flow in the perfused rat liver.
AB  - Influx of Ca2+ induced by the synergistic action of glucagon plus vasopressin in
      the perfused rat liver was progressively inhibited by infusing increasing
      concentrations of Ni2+ to the perfusion medium. The onset of Ca2+ influx
      following vasopressin administration was delayed and inhibition occurred of both
      the initial rate of Ca2+ influx as well as the total amount of Ca2+ taken up by
      the liver. Inhibition of the Ca2+ influx rate was almost maximal at approximately
      500 microM Ni2+; half-maximal inhibition occurred at less than 250 microM. Added
      Ni2+ also delayed the onset of the early transient bile flow peak. In addition,
      the duration of the transient peak in bile flow was prolonged by approximately 2
      min by all concentrations of Ni2+ between 25-500 microM, the greatest amount of
      bile being released in the presence of 250 microM Ni2+. Concentrations of Ni2+ at
      100 microM and above also inhibit the decrease in bile flow to below baseline
      levels. The data identify a multiple role for Ca2+ mobilisation in bile flow.

PMID- 8529263
TI  - Simultaneous measurements of exocytosis and intracellular calcium concentration
      with fluorescent indicators in single pituitary gonadotropes.
AB  - Previously, we established a method for the estimation of exocytosis in single
      gonadotropes using an impermeable fluorescent membrane probe, TMA-DPH. In this
      study, we have developed a method for the simultaneous measurement of exocytosis
      and intracellular free Ca2+ concentration ([Ca2+]i) by double-labeling with TMA
      DPH and the intracellular Ca2+ probe, Fura-2/AM, using a fluorescence microscope
      with a 3-wavelength excitation and 2-wavelength emission system. We, therefore,
      clarified the relationship between spontaneous [Ca2+]i oscillation or
      gonadotropin releasing hormone (GnRH)-induced intracellular Ca2+ mobilization and
      exocytosis in gonadotropes. Under resting conditions, some gonadotropes showed
      various types of spontaneous [Ca2+]i oscillations, while others did not, but all
      showed basal exocytosis. Each [Ca2+]i peak oscillation did not cause Ca(2+)
      regulated exocytosis, and even complete blockage of the [Ca2+]i increase by the
      intracellular Ca2+ chelator BAPTA/AM had no effect on basal exocytosis. Both GnRH
      induced intracellular Ca2+ mobilization and regulated exocytosis showed a similar
      pattern of peaks and plateaus. Blockage of the [Ca2+]i increase by BAPTA/AM
      almost completely inhibited the GnRH-stimulated exocytosis. These results show
      that spontaneous [Ca2+]i oscillations under resting conditions are not linked to
      regulated or basal exocytosis, and that intracellular Ca2+ mobilization is
      essential for GnRH-stimulated exocytosis.

PMID- 8529264
TI  - Both activators and inhibitors of protein kinase C promote the inhibition of
      phenylephrine-induced [Ca2+]i oscillations in single intact rat hepatocytes.
AB  - In single isolated rat hepatocytes Ca(2+)-mobilising hormones induce oscillations
      in cytosolic free Ca2+ ([Ca2+]i) in which the frequency of spiking depends on
      agonist dose, but the time course of individual spikes depends on the hormone
      species, rather than agonist concentration. We have previously presented data
      using sphingosine and staurosporine as evidence of a negative feedback role for
      protein kinase C (PKC) in the elongation of the falling phase of [Ca2+]i spikes.
      We show here that the principal effect of three specific PKC inhibitors, namely
      the bis-indolylmaleimide GF 109203X, the tetracyclic aromatic alkaloid
      chelerythrine, and a myristoylated PKC pseudosubstrate peptide, that act at
      different sites on the PKC molecule, is a reduction in, or a complete suppression
      of, the phenylephrine-induced [Ca2+]i oscillation frequency. These results
      resemble the effects of activators of PKC and modulators of diacylglycerol (DAG)
      metabolism. Furthermore, following phorbol ester-induced inhibition of the
      hepatocyte [Ca2+]i oscillator, the addition of all three of these PKC inhibitors
      further reduces the [Ca2+]i oscillation frequency, with high concentrations of
      chelerythrine being the only agent that overcomes this inhibition by phorbol
      ester. These paradoxical results point to the need for caution in interpreting
      the effects of protocols involving PKC activators and inhibitors in assessing the
      feedback control from PKC on cellular [Ca2+]i oscillations.

PMID- 8529265
TI  - The whoosh and trickle of calcium signalling.
AB  - The importance of phospholipase C catalysed hydrolysis of phosphatidylinositol
      (4,5)bisphosphate (PtdIns(4,5)P2) to inositol-(1,4,5)trisphosphate (Ins(1,4,5)P3)
      and sn-1,2-diacylglycerol in the signal transduction pathways of eukaryote cells,
      in response to extracellular stimuli, is now widely recognised. Although nearly
      60 naturally occurring inositol phosphates have been identified in mammalian
      cells, mobilisation of Ca2+ from the intracellular stores has been most commonly
      attributed to the generation of Ins(1,4,5)P3 [1]. However, there is increasing
      evidence for the presence of ryanodine receptors (RyR) in non-excitable cells and
      for cADP-ribose (cADPr) as the signalling molecule responsible for Ca2+ release
      via the RyR. But what is the purpose for the co-existence of these two
      intracellular Ca2+ channels in non-excitable cells and why are they so
      heterogeneous in their distribution? These questions were explored at the recent
      International Symposium Calcium Signalling in Inflammatory Cells. Depletion of
      the intracellular Ca2+ pools is followed by entry of Ca2+ into the cell across
      the plasma membrane, but the mechanism(s) underlying this 'capacitative Ca2+
      entry' is not well understood. Many potential signalling pathways which may
      account for capacitative Ca2+ entry have been proposed although none have been
      unanimously accepted. New developments in the elucidation of the mechanism
      responsible for capacitative Ca2+ entry and how Ca2+ entry is regulated, together
      with progress in the characterisation of plasma membrane Ca2+ entry channels were
      also discussed at this symposium.

PMID- 8529266
TI  - Mitochondrial transcription initiation: promoter structures and RNA polymerases.
AB  - A diversity of promoter structures. It is evident that tremendous diversity
      exists between the modes of mitochondrial transcription initiation in the
      different eukaryotic kingdoms, at least in terms of promoter structures. Within
      vertebrates, a single promoter for each strand exists, which may be
      unidirectional or bidirectional. In fungi and plants, multiple promoters are
      found, and in each case, both the extent and the primary sequences of promoters
      are distinct. Promoter multiplicity in fungi, plants and trypanosomes reflects
      the larger genome size and scattering of genes relative to animals. However, the
      dual roles of certain promoters in transcription and replication, at least in
      yeast, raises the interesting question of how the relative amounts of RNA versus
      DNA synthesis are regulated, possibly via cis-elements downstream from the
      promoters. Mitochondrial RNA polymerases. With respect to mitochondrial RNA
      polymerases, characterization of human, mouse, Xenopus and yeast enzymes suggests
      a marked degree of conservation in their behavior and protein composition. In
      general, these systems consist of a relatively non-selective core enzyme, which
      itself is unable to recognize promoters, and at least one dissociable specificity
      factor, which confers selectivity to the core subunit. In most of these systems,
      components of the RNA polymerase have been shown to induce a conformational
      change in their respective promoters and have also been assigned the role of a
      primase in the replication of mtDNA. While studies of the yeast RNA polymerase
      have suggested it has both eubacterial (mtTFB) and bacteriophage (RPO41) origins,
      it is not yet clear whether these characteristics will be conserved in the
      mitochondrial RNA polymerases of all eukaryotes. mtTFA-mtTFB; conserved but
      dissimilar functions. With respect to transcription factors, mtTFA has been found
      in both vertebrates and yeast, and may be a ubiquitous protein in mitochondria.
      However, the divergence in non-HMG portions of the proteins, combined with
      differences in promoter structure, has apparently relegated mtTFA to alternative,
      or at least non-identical, physiological roles in vertebrates and fungi. The
      relative ease with which mtTFA can be purified (Fisher et al. 1991) suggests
      that, where present, it should be facile to detect. mtTFB may represent a
      eubacterial sigma factor adapted for interaction with the mitochondrial RNA
      polymerase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8529267
TI  - The S. cerevisiae nuclear gene SUV3 encoding a putative RNA helicase is necessary
      for the stability of mitochondrial transcripts containing multiple introns.
AB  - The product of the nuclear gene SUV3 is implicated in a variety of post
      transcriptional processes in yeast mitochondria. We have analysed the effect of
      SUV3 gene-disruption on the expression of intron-containing alleles of the
      mitochondrial cytb and cox1 genes. We have constructed several strains with
      mitochondrial genomes containing different combinations of cytb and cox1 introns,
      and associated these genomes with the disruption of SUV3. The resulting strains
      were tested for their respiratory competence and spectral cytochrome content. All
      the strains containing only two or three introns showed normal expression of cytb
      and cox1, whereas the strains containing more introns were unable to express the
      appropriate gene. The analysis of mitochondrial RNAs by Northern hybridisation
      showed that the loss of respiratory competence in the strains containing more
      introns is due to the decrease of mRNA level with no over-accumulation of high
      molecular-weight precursors. However, the transcription of the genes was not
      affected. These results led us to the notion that SUV3 is required for the
      stability of intron-containing cytb and cox1 transcripts in a cumulative way, not
      dependent on any particular intron.

PMID- 8529268
TI  - Linear mitochondrial genome organization in vivo in the genus Pythium.
AB  - Pulsed-field gel electrophoresis (PFGE) of isolates of Pythium oligandrum with
      linear mitochondrial genomes revealed a distinct band in ethidium bromide-stained
      gels similar in size to values estimated by restriction mapping of mitochondrial
      DNA (mtDNA). Southern analysis confirmed that these bands were mtDNA and
      indicated that linear genomes were present in unit-length size as well as
      multimers. Isolates of this species with circular mtDNA restriction maps also had
      low levels of linear mono- and multimers visualized by Southern analysis of PFGE
      gels. Examination of 17 additional species revealed similar results; three
      species had distinct linear mtDNA bands in ethidium bromide-stained gels while
      the remainder had linear mono- and multi-mers in lower amounts detected only by
      Southern analysis. Sequence analysis of an isolate of P. oligandrum with a
      primarily circular mitochondrial genomic map and a low amount of linear molecules
      revealed that the small unique region of the circular map (which corresponded to
      the terminal region of linear genomes) was flanked by palindromic intrastrand
      complementary sequences separated by a unique 194-bp sequence. Sequences with
      similarity to ATPase9 coding regions from other organisms were located adjacent
      to this region. Sequences with similarity to mitochondrial origins of replication
      and autonomously replicating sequences were also located in this region: their
      potential involvement in the generation of linear molecules is discussed.

PMID- 8529269
TI  - Physical and gene organization of mitochondrial DNA from the fertile cytoplasm of
      sugarbeet (Beta vulgaris L.).
AB  - We have constructed a complete physical map of the mitochondrial genome from the
      male-fertile cytoplasm of sugarbeet. The entire sequence complexity can be
      represented on a single circular master chromosome of 358 kb. This master
      chromosome contains three copies of one recombinationally active repeat sequence,
      with two copies in direct orientation and the other in inverted orientation. The
      positions of the rRNA genes and of 23 polypeptide genes, determined by filter
      hybridization, are scattered throughout the genome, with triplicate rrn26 genes
      located partially or entirely within the recombination-repeat elements. Three
      ribosomal-protein genes (rps1A, rps14 and rps19) were found to be absent from
      sugarbeet mtDNA. Our results also reveal that at least six regions homologous
      with cDNA are dispersed in the mitochondrial genome.

PMID- 8529270
TI  - Mitochondrial DNA sequences reveal close relationships between social parasitic
      ants and their host species.
AB  - In the tribe Leptothoracini, the phylogenetic relationship of socially parasitic
      ants (Doronomyrmex kutteri, D. goesswaldi and Harpagoxenus sublaevis) and their
      host species Leptothorax acervorum has been controversial. Even more
      controversial is the relationship between the socially parasitic ant Chalepoxenus
      muellerianus and its host species Leptothorax unifasciatus, L. nigriceps, L.
      interruptus and L. recedens. On the basis of morphological, ecological and
      ethological criteria it has been argued that socially parasitic ants and their
      respective hosts always evolved from common ancestors, and hence it has been
      postulated that these species should be included in common taxonomical groups.
      This would require the division of the tribe Leptothoracini into two subgroups,
      one comprising the subgenus Leptothorax (s. str.) and the other the subgenus
      Myrafant, together with their respective parasitic genera. We have used the
      polymerase chain reaction (PCR) to compare a 360-bp sequence of the mitochondrial
      cytochrome b gene of 14 species belonging to the tribe Leptothoracini and an
      outgroup species Tetramorium impurum (Tetramoriini). The results generally agree
      with the morphological studies which suggest that a common ancestral species
      differentiated into host and parasite species. This relationship is very obvious
      within the Leptothorax (s. str.) group but less pronounced in the species
      belonging to the Myrafant group. Leptothorax (Temnothorax) recedens shows a
      greater sequence divergence than the outgroup species T. impurum.

PMID- 8529271
TI  - Characterization of peroxisome-deficient mutants of Hansenula polymorpha.
AB  - In the methylotrophic yeast Hansenula polymorpha, approximately 25% of all
      methanol-utilization-defective (Mut-) mutants are affected in genes required for
      peroxisome biogenesis (PER genes). Previously, we reported that one group of per
      mutants, termed Pim-, are characterized by the presence of a few small
      peroxisomes with the bulk of peroxisomal enzymes located in the cytosol. Here, we
      describe a second major group of per mutants that were observed to be devoid of
      any peroxisome-like structure (Per-). In each Per- mutant, the peroxisomal
      methanol-pathway enzymes alcohol oxidase, catalase and dihydroxyacetone synthase
      were present and active but located in the cytosol. Together, the Pim- and Per-
      mutant collections involved mutations in 14 different PER genes. Two of the
      genes, PER5 and PER7, were represented by both dominant-negative and recessive
      alleles. Diploids resulting from crosses of dominant per strains and wild-type H.
      polymorpha were Mut- and harbored peroxisomes with abnormal morphology. This is
      the first report of dominant-negative mutations affecting peroxisome biogenesis.

PMID- 8529272
TI  - MIG1-dependent and MIG1-independent glucose regulation of MAL gene expression in
      Saccharomyces cerevisiae.
AB  - Glucose repression is a global regulatory system in Saccharomyces cerevisiae
      controlling carbon-source utilization, mitochondrial biogenesis, gluconeogenesis
      and other metabolic pathways. Mig1p, a zinc-finger class of DNA-binding protein,
      is a transcriptional repressor regulating GAL and SUC gene expression in response
      to glucose. This report demonstrates that Mig1 protein represses transcription of
      the MAL61 and MAL62 structural genes and also the MAL63 gene, which encodes the
      Mal-activator. Mig1p DNA-binding sites were identified upstream of all three MAL
      genes. Both of the Mig1p-binding sites found in the bidirectional MAL61-MAL62
      promoter were shown to function in the Mig1p-dependent glucose repression.
      Studies using constitutive Mal-activator alleles suggest that glucose regulation
      of inducer availability is a second major contributing factor in glucose
      repression of MAL gene expression and is even stronger than the Mig1p-dependent
      component of repression. Moreover, our results also suggest the contribution of
      other minor mechanisms in glucose regulation of MAL gene expression.

PMID- 8529273
TI  - Carbon catabolite regulation of transcription of nuclear genes coding for
      mitochondrial proteins in the yeast Kluyveromyces lactis.
AB  - Promoter regions of the KlQCR7, KlQCR8 and KlCYC1 genes, coding for subunits of
      the bc1-complex and cytochrome c respectively, in the short-term Crabtree
      negative yeast Kluyveromyces lactis differ markedly in sequence from their
      Saccharomyces cerevisiae counterparts. They have, however, conserved very similar
      configurations of binding-site motifs for various transcription factors known to
      be involved in global and carbon-source regulation in S. cerevisiae. To
      investigate the carbon source-dependent expression of these genes in K. lactis,
      we have carried out medium-shift experiments and determined transcript levels
      during the shifts. In sharp contrast to the situation in S. cerevisiae, the level
      of expression in K. lactis is not affected when glucose is added to a non
      fermentable carbon-source medium. However, the genes are not constitutively
      expressed, but become significantly induced when the cells are shifted from
      glucose to a non-fermentable carbon source. Finally, induction of transcriptional
      activation does not occur in media containing both glucose and non-fermentable
      carbon sources.

PMID- 8529274
TI  - RAD58 (XRS4)--a new gene in the RAD52 epistasis group.
AB  - The RAD58 (XRS4) gene of Saccharomyces cerevisiae has been previously identified
      as a DNA repair gene. In this communication, we show that RAD58 also encodes an
      essential meiotic function. The spore inviability of rad58 strains is not rescued
      by a spo13 mutation. The rad50 mutation suppresses spore inviability of a spo13
      rad58 strain suggesting that RAD58 acts after RAD50 in meiotic recombination. The
      rad58-4 mutation does not prevent mitotic recombination events. Haploid rad58
      cells fail to carry out G2-repair of gamma-induced lesions, whereas rad58/rad58
      diploids are able to perform some diploid-specific repair of these lesions.

PMID- 8529275
TI  - Migration of the yeast linear DNA plasmid from the cytoplasm into the nucleus in
      Saccharomyces cerevisiae.
AB  - The Kluyveromyces linear plasmids, pGKL1 and pGKL2, carrying terminal protein
      (TP), are located in the cytoplasm and have a unique gene expression system with
      the plasmid-specific promoter element termed UCS, which functions only in the
      cytoplasm. In this study we have developed an in vivo assay system in
      Saccharomyces cerevisiae which enables the detection of a rare migration of the
      yeast cytoplasmic plasmid to the nucleus, using a pGKL1-derived cytoplasmic
      linear plasmid pCLU1. pCLU1 had both the UCS-fused LEU2 gene (a cytoplasmic
      marker) and the native URA3 gene (a nuclear marker) and therefore its cytoplasmic
      nucleo localized could be determined by the phenotypic analysis of the marker.
      The nuclearly migrated plasmids were often detected as linear plasmids having the
      telomere sequence of the host yeast at both ends, although circular plasmids were
      also found. The circular form was produced by the the terminal fusion of pCLU1.
      Insertion of a Ty element into a nuclearly migrated plasmid was observed,
      allowing the ROAM-regulated expression of the adjacent nuclearly silent UCS-fused
      LEU2 gene. The nuclearly located plasmids, whether linear or circular, were less
      sensitive to UV-mediated curing than pGKL and pCLU1.

PMID- 8529276
TI  - Molecular phylogeny of the fungi of the Iceman's grass clothing.
AB  - To investigate the origin of the fungal hyphae that cover the grass clothing
      (cloak, boots) found near the neolithic mummy known as the Tyrolean Iceman, two
      radiocarbon-dated samples of grass were submitted to DNA extraction. The DNA was
      then PCR amplified using, respectively, primers specific for the region
      containing the internal transcribed spacers and the 5.8s rDNA (ITS), and primers
      specific for an approximately 600-bp long fragment of the nuclear small-subunit
      ribosomal DNA (SSU rDNA) repeat units of eukaryotes. The amplification products
      were cloned and sequenced. Sequence analysis of 20 individual ITS clones and of
      ten SSU rDNA clones indicated that three types of fungal DNA can be extracted
      from the grass. Phylogenetic analyses, using 5.8s and SSU rDNA fungal reference
      sequences from EMBL and GenBank databases, suggest that the DNAs come,
      respectively, from a psychrophilic basidiomycetous yeast, phylogenetically close
      to Leucosporidium scottii, and from two ascomycetes, one of which is possibly
      related to the Eurotiales.

PMID- 8529277
TI  - Maternal anthropometry and pregnancy outcomes. A WHO Collaborative Study.
AB  - The nutritional status of a woman before and during pregnancy is critical to both
      her infant's and her own health and survival. It determines her well-being and
      that of the fetus and child, and in turn the health and reproductive capacity of
      the next generation's mothers. Anthropometric assessment of nutritional status
      during the reproductive cycle, particularly during pregnancy, is a widely used,
      low-technology procedure that has seldom been rigorously evaluated. The need to
      provide sound technical advice on the utility and feasibility of selected
      anthropometric indicators for routine application in primary health care,
      especially in circumstances where resources are limited, led to a meta-analysis
      of 25 data sets on maternal anthropometry and pregnancy outcomes from 20
      different countries, providing information on more than 111,000 births and
      quantifying to what degree anthropometric measurements are useful and efficient
      in predicting maternal and child outcomes of pregnancy in the community and at
      home in different country settings. The next stage will be the demonstration of
      the operational value of the findings of this study through their successful
      application in service settings on a large scale.

PMID- 8529278
TI  - Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion
      topotecan in children with central nervous system tumors.
AB  - The purpose of this study was to describe the cerebrospinal fluid (CSF)
      penetration of topotecan in humans, to generate a pharmacokinetic model to
      simultaneously describe topotecan lactone and total concentrations in the plasma
      and CSF, and to characterize the CSF and plasma pharmacokinetics of topotecan
      administered as a continuous infusion (CI). Plasma and CSF samples were collected
      from 17 patients receiving 5.5 or 7.5 mg/m2 per day as a 24-h CI (5 patients, 7
      courses), or 0.5 to 1.25 mg/m2 per day as a 72-h CI (12 patients, 12 courses).
      CSF samples were obtained from either a ventricular reservoir (VR) or a lumbar
      puncture (LP). Topotecan lactone and total (lactone plus hydroxy acid)
      concentrations were determined by HPLC and fluorescence detection. Using MAP
      Bayesian modelling, a three-compartment model was fitted simultaneously to
      topotecan lactone and total concentrations in the plasma and CSF. The penetration
      of topotecan into the CSF was determined from the ratio of the CSF to the plasma
      area under the concentration-time curve. The median CSF ventricular lactone
      concentrations, obtained prior to the end of infusion (EOI), were 0.86, 1.4,
      0.73, 5.3, and 4.6 ng/ml for patients receiving 0.5, 1.0, 1.25, 5.5, and 7.5
      mg/m2 per day, respectively. EOI CSF lumbar lactone concentrations measured in
      three patients were 0.44, 1.1, and 1.7 ng/ml for topotecan doses of 1.0, 5.5, and
      7.5 mg/m2 per day, respectively. In two patients receiving 1.25 mg/m2 per day,
      EOI CSF concentrations were obtained simultaneously from a VR and LP; the lumbar
      lactone concentrations were 30% and 49% lower than the ventricular
      concentrations. During a 24-h and a 72-h CI, the median CSF penetration of
      topotecan lactone was 0.29 (range 0.10 to 0.59) and 0.42 (range 0.11 to 0.86),
      respectively. A three-compartment model adequately described topotecan lactone
      and total concentrations in the plasma and CSF. Topotecan was therefore found to
      significantly penetrate into the CSF in humans. The pharmacokinetic model
      presented may be useful in the design of clinical studies of topotecan to treat
      CNS tumors.

PMID- 8529279
TI  - A microcomputer program for calculating cell population doubling time in vitro
      and in vivo.
AB  - Determination of the doubling time for a population of cells can involve tedious
      calculations. We have developed computer software for MS-DOS microcomputers to
      expedite the analysis of tumor cell growth in vitro and in vivo. This program,
      DOUBLE-TIME, assists in the collection of cell numbers into a database and
      calculates the doubling time for a population of cells from the plot of cell
      growth over time. For experiments where tumor mass is measured in vivo, the
      software collects measurements of tumor size, calculates tumor volume (mass),
      generates growth curves for tumor volume change over time, and determines the
      doubling time of the tumor and the mean for multiple tumors. DOUBLE-TIME plots
      both total and viable cell numbers over time, calculates standard error of the
      doubling time, and the doubling time for a selected portion of a growth curve.
      This software also automates the cell counting process with a software-generated
      cell counter that allows cell counts to be tallied directly into the computer via
      a mouse.

PMID- 8529280
TI  - Antitumor activity of treosulfan in human lung carcinomas.
AB  - Treosulfan (L-threitol 1,4-bismethanesulfonate, Ovastat) is an alkylating agent
      and a structural analogue of busulfan. It has been established in the clinical
      chemotherapy of human ovarian carcinomas for several years and has additionally
      been shown to be effective against xenografted human breast carcinomas. No other
      human carcinoma is yet known to be sensitive to treosulfan. The present study
      confirms the pronounced and significant antitumor activity of treosulfan against
      heterotransplanted human lung carcinomas of both the small-cell and the non-small
      cell type. Treosulfan reduced the growth of all four small-cell lung carcinomas
      that were investigated in a significant manner. It was even more active than
      equitoxic doses of the clinically approved cytostatics ifosfamide, cisplatin, and
      etoposide toward three of them and induced long-lasting growth reductions (60-98%
      of control tumor size) corresponding to partial and nearly complete remissions.
      In the case of the nine non-small-cell lung carcinomas investigated, treosulfan
      effected significant growth inhibition of more than 50%, again in all of them,
      and was more active than the comparative compounds ifosfamide, mitomycin C, and
      cisplatin at least in one of four epidermoid lung carcinomas, one large-cell
      carcinoma, and one of three lung adenocarcinomas. These results are remarkable
      and unexpected, and the present study should be followed rapidly by phase II
      clinical trials of treosulfan against human lung carcinomas of both the small
      cell and the non-small-cell type.

PMID- 8529281
TI  - Schedule-dependent synergism of taxol or taxotere with edatrexate against human
      breast cancer cells in vitro.
AB  - A new dihydrofolate reductase inhibitor, edatrexate (EDX), and the microtubule
      polymerization promotor, taxol (TXL) or taxotere (TXT), each have significant
      therapeutic activity against human breast cancer in clinical trials. Since they
      also have distinctly different mechanisms of actions and have mainly non
      overlapping toxicities, they may be effective in combination in the treatment of
      this disorder. Schedule-dependent interactions between these taxanes and EDX
      against human breast adenocarcinoma cells (SK-Br-3) were quantitatively assessed
      in vitro to determine whether these interactions are synergistic or antagonistic.
      SK-Br-3 cells were grown as a monolayer in 96-well microplates. The dose-effect
      relationships of the drugs, singly and in combination, in inhibiting the growth
      over a 7-day period were determined by the SRB protein staining assays. Cell
      cultures were exposed to drug as a 3-h pulse at either 0-3 h or 24-27 h.
      Synergism or antagonism at different concentrations and at different effect
      levels were assessed with the median effect principle and the combination index
      isobologram method using computer software. These methods were selected because
      they take into account both the potencies and the shape of the dose-effect
      curves. Exposure of cells to an equimolar combination of EDX + TXL (0-3 h)
      resulted in synergism at high effect levels. Pretreatment of cells with EDX (0-3
      h) followed by TXL (24-27 h) showed even greater synergism in inhibiting cell
      growth. Moderate antagonism was observed with the reverse schedule. EDX + TXT (0
      3 h) was additive, but pretreatment with EDX (0-3 hr) followed by TXT (24-27 h)
      showed synergism. However, the reverse order showed antagonism. Studies on
      another breast tumor cell line, ZR-57-1, also showed the schedule of EDX (0-3 h)
      + TXT or TXL (24-27 h) to be more synergistic than, the other two schedules
      examined. These results show potent schedule-dependent synergism of the
      combinations of TXL or TXT with EDX, and should form a rationale for designing
      clinical protocols utilizing these agents particularly for the treatment of
      breast cancer patients.

PMID- 8529282
TI  - Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6
      methylmercaptopurine ribonucleoside.
AB  - Inhibition of pyrimidine and purine synthesis has been demonstrated to potentiate
      5-fluorouracil (5-FU) activity in preclinical models. Low-dose phosphonacetyl-L
      aspartate (PALA) potentiates the incorporation of 5-FU into RNA, without
      detectably increasing its toxicity. 6-Methylmercaptopurine riboside (MMPR)
      results in inhibition of purine biosynthesis with elevation of phosphoribosyl
      pyrophosphate (PRPP), which in turn is believed to increase the phosphorylation
      and intracellular retention of 5-FU. We conducted a phase I clinical trial to
      determine the maximum tolerated dose of 5-FU in combination with low-dose PALA
      and a biochemically-optimized dose of MMPR. The regimen consisted of PALA 250
      mg/m2 given on day 1, followed 24 h later by MMPR 150 mg/m2, and escalating doses
      of 5-FU from 1625 to 2600 mg/m2 by 24 h continuous infusion. This regimen was
      repeated weekly. A group of 29 patients with a diagnosis of malignant solid tumor
      were entered; their median performance status was 1. The dose-limiting toxicity
      was mucositis, while other gastrointestinal toxicity was minimal. Two patients
      also experienced ischemic chest pain during the 5-FU infusion. The maximum
      tolerated dose of 5-FU in this combination was 2600 mg/m2. Several responses were
      observed including a complete remission in a previously treated breast cancer
      patient and two partial responses in breast and colon cancer. MMPR
      pharmacokinetics were obtained from urine analyses in 21 patients on this trial;
      there was no correlation between the pharmacokinetics of MMPR and the toxicity
      observed. This regimen was well tolerated and phase II trials are warranted using
      PALA 250 mg/m2, MMPR 150 mg/m2, and 5-FU 2300 mg/m2 by continuous infusion over
      24 h.

PMID- 8529283
TI  - Multi-chemothermoimmunotherapy for human colon adenocarcinoma in vitro.
AB  - Effective adjunctive therapies for colorectal carcinoma are clearly needed. We
      evaluated the cytotoxic responses in vitro of human colon carcinoma cell lines to
      combined modalities: 5-fluorouracil/leucovorin (5-FU/LV), carboplatin (CP), tumor
      necrosis factor (TNF) and hyperthermia (HTX). Cytotoxicity was evaluated in a
      cell proliferation assay using crystal violet staining. 5-FU/LV was administered
      2-3 days before TNF and CP, followed 1 h later by HTX. These cell lines were
      relatively resistant to HTX alone (42 degrees C for 2 h), but were heterogeneous
      in their responses to various doses of the other single agents. This
      heterogeneity was also evident for combined modalities: the HCT-15 cell line
      exhibited significant supra-additivity for selected doses of CP, TNF and 5-FU/LV,
      which was further enhanced by hyperthermia. In contrast, the HT-29 cell line did
      not demonstrate a strong pattern for supra-additivity, whereas the DLD-1 cell
      line had an intermediate response. Thus, our results suggest one approach to
      develop effective and dose-sparing multimodality therapeutic regimens for colon
      adenocarcinoma.

PMID- 8529284
TI  - Repair analysis of 4-hydroperoxycyclophosphamide-induced DNA interstrand
      crosslinking in the c-myc gene in 4-hydroperoxycyclophosphamide-sensitive and 
      resistant medulloblastoma cell lines.
AB  - Cyclophosphamide is one of the most active agents in the treatment of
      medulloblastoma. However, development of resistance to this alkylator frequently
      occurs and is the harbinger of tumor progression and death. In order to
      understand the biochemical basis of this resistance, we generated a panel of
      medulloblastoma cell lines in our laboratory that were resistant to 4
      hydroperoxycyclophosphamide (4-HC). Previously, we have shown that elevated
      levels of aldehyde dehydrogenase and glutathione mediate cellular resistance to 4
      HC. The present study was conducted to identify the third unknown mechanism
      mediating the resistance of cell line D283 Med (4-HCR) to 4-HC, testing the
      hypothesis that this resistance is mediated by an increased repair of DNA
      interstrand crosslinks (ICLs). The doses of 4-HC that produced a one- and two-log
      cell kill of D283 Med cells were 25 and 50 microM, respectively, compared with
      values of 125 and 165 microM in D283 Med (4-HCR), the resistant cell line. The
      formation and disappearance of 4-HC-induced DNA ICLs at the c-myc gene were
      subsequently studied by DNA denaturing/renaturing gel electrophoresis and
      Southern blot analysis. 4-HC-induced DNA ICLs in the c-myc gene exhibited a dose
      dependent relationship. The percentage of the c-myc gene that was crosslinked was
      approximately 1-3% at a dose of 100 microM. More than 50% of the DNA crosslinking
      in D283 Med (4-HCR) cells was removed by 6 h after drug treatment, whereas, in
      D283 Med cells, more than 90% of the DNA crosslinking was still present at 6 h.
      These findings suggest that the increased repair of DNA ICLs in D283 Med (4-HCR)
      may contribute significantly to its resistance to 4-HC.

PMID- 8529285
TI  - Busulfan disposition and hepatic veno-occlusive disease in children undergoing
      bone marrow transplantation.
AB  - Hepatic veno-occlusive disease (HVOD) is a frequent life-threatening toxicity in
      patients undergoing bone marrow transplantation (BMT) after the administration of
      a high-dose busulfan-containing regimen. Recent studies have shown that the
      morbidity and mortality of HVOD may be reduced in adults by pharmacologically
      guided dose adjustment of busulfan. We analyzed the pharmacodynamic relationship
      between busulfan disposition and HVOD in 61 children (median age, 5.9 years) with
      malignant disease. Busulfan, given at a dose ranging from 16 mg/kg to 600 mg/m2,
      was combined with one or two other alkylating agents (cyclophosphamide,
      melphalan, thiotepa). Only 3 patients received the standard
      busulfan/cyclophosphamide (BUCY) regimen. A total of 24 patients (40%) developed
      HVOD, which resolved in all cases. A pharmacokinetics study confirmed the
      previously reported wide interpatient variability in busulfan disposition but did
      not reveal any significant alteration in children with HVOD. The mean area under
      the concentration-time curve (AUC) after the first dose of busulfan was higher in
      patients with HVOD (6,811 +/- 2,943 ng h ml-1) than in patients without HVOD
      (5,760 +/- 1,891 ng h ml-1., P = 0.10). This difference reflects the higher dose
      of busulfan given to patients with HVOD. No toxic level could be defined and,
      moreover, none of the toxic levels identified in adults were relevant. The high
      incidence of HVOD in children given 600 mg/m2 busulfan may be linked to the use
      of more intensive than usual high-dose chemotherapy regimens and/or drug
      interactions. Before the prospective evaluation of busulfan dose adjustment in
      children, further studies are required to demonstrate firmly the existence of a
      pharmacodynamic relationship in terms of toxicity and allogeneic engraftment,
      especially when busulfan is combined with cyclophosphamide. The maximal tolerated
      and minimal effective AUCs in children undergoing BMT are likely to depend mainly
      upon the disease, the nature of the combined high-dose regimen, and the type of
      bone marrow transplant.

PMID- 8529286
TI  - Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic
      breast cancer.
AB  - Triciribine is a purine analogue which inhibits DNA and protein synthesis. We
      performed two studies to define its activity against metastatic breast cancer.
      The first study was a phase II study in 14 patients with metastatic breast cancer
      who had received two or fewer chemotherapy treatments. The treatment schedule was
      tricirbine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks
      as recommended by a previous open phase I trial. When neither response nor
      toxicity was seen in the phase II trial, we assumed the starting dose was too low
      for this group of patients with good performance status and repeated the phase I
      trial in patients with metastatic breast cancer with good performance status. The
      starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting
      doses were increased in subsequent cohorts of three patients in increments of 5
      mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had
      stable disease for 18 weeks (three courses), the remainder progressed. There were
      no significant toxic effects. In the subsequent phase I study, ten patients were
      treated until the study was closed. The maximum dose was 40 mg/m2. Two patients
      died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks
      after their last course, one without intervening disease progression. Both had
      severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At
      postmortem examination, one had congestive cardiomyopathy, and the other had
      severe pancreatitis and hypothyroidism. One patient had severe exacerbation of
      psoriasis which made her bedridden for more than 30 days. Four patients had
      hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably
      related to enterohepatic circulation. Postmortem pharmacology studies showed
      residual drug present as long as 12 weeks after the last dose. We conclude that
      triciribine is ineffective at all doses tested and at doses of > or = 35 mg/m2
      has unacceptable toxic effects.

PMID- 8529287
TI  - 5-Fluorouracil metabolism and cytotoxicity after pre-treatment with methotrexate
      or thymidine in human hypopharynx and colon carcinoma xenografts: a 19F-nuclear
      magnetic resonance spectroscopy study in vivo.
AB  - The metabolism of 5-fluorouracil (5-FU) was monitored non-invasively in two
      xenografts, a hypopharynx carcinoma and a colon carcinoma (CSM) by 19F-magnetic
      resonance spectroscopy following an i.v. bolus injection of 130 mg kg-1 5-FU.
      Both the level of fluoronucleotides (FNuc) and the tumor growth delay were
      significantly higher in the CSM colon carcinoma than in the hypopharynx carcinoma
      (both parameters, P < 0.001). Administration of 100 mg kg-1 methotrexate (MTX) at
      15 h before treatment with 5-FU caused a significantly increased conversion of 5
      FU to FNuc in both tumors (P < 0.05) as compared with the application of 5-FU
      alone. However, only in the CSM tumor was a significantly increased growth delay
      (P < 0.01) observed. Pre-treatment of both xenografts with 400 mg kg-1 thymidine
      enhanced the conversion of 5-FU to FNuc in both tumors. In the CSM tumour this
      treatment modality caused a significantly (P < 0.05) higher growth delay as
      compared with the results obtained with 5-FU alone, whereas in the hypopharynx
      carcinoma the additional application of thymidine caused no significant change in
      tumor growth. It is known that both thymidine and MTX can reduce the DNA-directed
      cytotoxicity of 5-FU, whereas the RNA-directed cytotoxicity is increased. It is
      concluded that the DNA-mediated toxicity may be more important in the hypopharynx
      carcinoma than in the CSM colon carcinoma. As a consequence, pre-treatment with
      MTX or thymidine enhances FNuc formation, although only in the CSM carcinoma is
      there an increased tumor growth delay. Thus, in the hypopharynx carcinoma the
      measurement of FNuc did not serve as a predictor for the treatment efficacy of
      the combined treatment modality. Pre-treatment with MTX did not influence the
      catabolism of 5-FU, whereas thymidine actually prolonged the half-life of 5-FU
      without alpha-fluoro-beta-alanine becoming detectable.

PMID- 8529288
TI  - Evaluation of formulas using the serum creatinine level to calculate the optimal
      dosage of carboplatin.
AB  - Carboplatin is a chemotherapeutic agent frequently used in the treatment of
      various malignancies. An individual dosing strategy has been recommended to yield
      the most optimal exposure, expressed as the area under the concentration-time
      curve (AUC). The formula developed by Calvert et al. (dose = target-AUC x [GFR +
      25]) can be used to achieve this. However, due to the inconvenient [51Cr]
      ethylenediamine-tetraacetic acid ([51Cr]-EDTA)-based measurement of the
      glomerular filtration rate (GFR), its application in the clinic has thus far been
      limited. Chatelut and co-workers have recently proposed a formula to estimate
      carboplatin clearance using the serum creatinine concentration. We
      retrospectively tested the Chatelut equation and the Calvert formula using either
      the creatinine clearance based on 24-h urine collection or the creatinine
      clearance based on the formula of Cockcroft and Gault. The latter equations were
      shown to predict the carboplatin clearance reasonably well, although systematic
      overprediction and underprediction occurred. However, the formula proposed by
      Chatelut and co-workers had no significant bias and was precise. It is proposed
      that this formula be used to calculate the optimal carboplatin dosage after
      prospective validation has been performed.

PMID- 8529289
TI  - Comparison of the antitumor activity of bryostatins 1, 5, and 8.
AB  - Bryostatin 1, a macrocyclic natural lactone isolated from a marine Bryozoan, has
      undergone phase I testing in humans. Side effects of treatment have included
      muscle pain and joint aches, a transient decrease in platelets, and the release
      of tumor necrosis factor alpha (TNF alpha) and IL-6 into the blood stream. In
      animals, anticancer activity has been demonstrated against murine leukemias,
      lymphomas, melanomas, and sarcomas. The mechanism of action of this compound
      depends in part on its ability to activate protein kinase C. To determine the
      biologic activity and toxicity of other members of the family of bryostatin
      compounds, we studied the ability of bryostatins 5 and 8 to inhibit the growth of
      murine melanoma K1735-M2. Bryostatins 1, 5, and 8 induced equivalent inhibition
      of melanoma growth, but bryostatins 5 and 8 induced less weight loss than
      bryostatin 1 (P < 0.001). Neither the injection of an antimurine TNF alpha
      antibody nor an adenovirus, which produces a mutated TNF receptor inhibiting TNF
      alpha activity, into mice had any effect on either bryostatin-induced weight loss
      or melanoma tumor growth inhibition. Using a novel competition assay, the levels
      of bryostatin in the plasma were measured. The approximate half-life (t1/2) of
      bryostatin was 8.62 min, the clearance (Cl) 3.53 ml/min and the AUC 322.20 nmol/l
      min. A similar result was obtained with each bryostatin analog. These results
      suggest that human testing of additional bryostatin analogs may yield compounds
      with similar antitumor activity but decreased side effects. A novel assay to
      measure the level of all bryostatins in the plasma of patients undergoing
      treatment is described.

PMID- 8529291
TI  - Effect of different mathematical methods on etoposide area under the curve
      estimations and pharmacodynamic response predictions.
AB  - Different methods to calculate interval area under the curve (AUC) data may
      produce substantial error. The purpose of this study was to compare methods of
      calculating etoposide AUC and determine the effect of these values on white blood
      cell (WBC) count nadir predictions calculated from a previously reported
      equation. Three AUC calculation methods were used: (1) the linear trapezoidal
      method, (2) a combination of the linear and logarithmic trapezoidal methods, and
      (3) the Lagrange method. Since none of the methods for determining the AUC could
      be considered the standard, the methods were evaluated by comparing differences
      between pairs of calculated AUC values by each method. The 95% CI for differences
      between all pairs of AUC values were greater than zero (no difference) indicating
      significance. Consistent with the smoother fitting function between data points,
      the Lagrange method tended to produce a larger AUC, lower clearance values, and
      lower WBC nadir count predictions than the other methods. The largest difference
      encountered was between the Lagrange and the linear-log AUC methods with a mean
      value of 16.9 micrograms h/ml (95% CI 9.4-24.3) This difference would account for
      approximately 11% of the total AUC. Using a previously published equation, where
      WBC nadir = -0.057 +0.048 x etoposide clearance, with clearance determined as
      dose/AUC, mean differences in calculated WBC nadir count values between the three
      AUC methods ranged from 80 to 220 cells/microliters, which would be expected to
      be of little clinical consequence. The precision of this equation, using data
      derived from linear trapezoidal AUC calculations, had a mean absolute error of
      0.93 x 10(3)/microliters (95% CI 0.53-1.32). Our findings suggest that any of the
      three mathematical methods studied would produce similar etoposide AUC values and
      pharmacodynamic predictions. Further, these findings also suggest that the major
      limitation in predicting etoposide leukopenia lies with the imprecision of the
      pharmacodynamic model more so than the ability to accurately determine the AUC.
      However, our findings may not be applicable if other factors intervene which
      dramatically alter the shape of the etoposide concentration-time curve.

PMID- 8529290
TI  - Comparison of the efficacy of tropisetron versus a metoclopramide cocktail based
      on the intensity of cisplatin-induced emesis.
AB  - Cisplatin-induced emesis is one of the most feared side effects in cancer
      treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute
      emesis. Investigations to test the efficacy of new antiemetics are mandatory. We
      compared the efficacy, toxicity, and patients' preference for tropisetron, a new
      5-hydroxytryptamine3 (HT3) receptor antagonist, with those of a combination of
      high-dose metoclopramide, dexamethasone, diphenhydramine, and lorazepam
      (metoclopramide cocktail) in a randomized crossover study for the control of
      nausea and vomiting during cisplatin-containing chemotherapy. A total of 62
      chemotherapy-naive women were included and followed over 3 consecutive courses.
      Detailed analysis comparing the incidence of acute emesis for each 4 h period
      following cisplatin infusion was also performed. Complete protection from acute
      emesis was obtained in 48% of patients receiving tropisetron and 29% of patients
      receiving the metoclopramide cocktail over the first two courses of chemotherapy
      (P = 0.029). When the frequency of acute emesis in all patients was compared on a
      daily basis, no significant difference was found. When emesis frequency was
      compared over each 4 h period following infusion of cisplatin, tropisetron was
      superior to the metoclopramide cocktail during the first, the second, and the
      first and second periods (P = 0.0001, P = 0.01 and P = 0.0006, respectively).
      This superiority reversed after 12 h but did not reach statistical significance
      (P = 0.112). Tropisetron was more effective in controlling acute nausea, but
      metoclopramide provided better control of delayed emesis. A drop in efficacy over
      successive courses was observed in patients receiving metoclopramide first but
      was not seen in tropisetron-first patients. A tendency for tropisetron preference
      was observed. Tropisetron is more effective than the metoclopramide cocktail in
      the control of chemotherapy-induced vomiting within 8 h of the implementation of
      cisplatin and in the control of nausea on the 1st day. To improve the control of
      chemotherapy-induced emesis, further investigations on the additional tropisetron
      dosing at 8 h after cisplatin infusion or the combination use of tropisetron and
      other antiemetics by a continuous 4 h period of observation and comparison are
      mandatory.

PMID- 8529292
TI  - Chronic childhood illnesses: what aspects of caregiving do parents value?
AB  - Parents of children with chronic illnesses are at significantly increased risk to
      experience mental health problems. Because such families are in frequent contact
      with the health care system, it is possible that aspects of the organization and
      content of health services might contribute to the development or prevention of
      these emotional burdens. The purpose of the present study was to examine the
      patterns of parental values about a variety of aspects of care and services,
      assessing both the absolute and relative importance of 22 defined components of
      care (COCs). Respondents were 80/111 parents (72%) of children with diabetes
      mellitus and 45/56 parents (80%) of children with cystic fibrosis, followed at a
      regional university-affiliated children's hospital. They completed a two-part
      mailed questionnaire, rating independently each COC, and then ranking all 22 COCs
      using a modified Q-sort technique. While the majority of COCs were judged as
      'somewhat' or 'very' important by over 75% of respondents, there was also
      significant agreement between the two groups on their rankings of the COCs
      (Spearman rank coefficient r = 0.92, P < 0.001). The COCs ranked most highly by
      both groups were diagnosis, treatment, education/information,
      continuity/consistency, accessible and available care, evaluation of chronic
      illness, and parental involvement. Furthermore, the concordance between this
      combined medical illness group and a previously-studied neurodevelopmental group
      was r = 0.72 (P < 0.001). These results are discussed in relation to the non
      categorical approach to longstanding childhood illness and disability.
      Implications for preventive mental health within the content and structure of
      health services are considered.

PMID- 8529293
TI  - Siblings of a child with autism, with mental retardation and with a normal
      development.
AB  - A total of 60 children between 8 and 15 years of age participated in this
      project, 20 of whom had a sibling with autism, 20 a sibling with mental
      retardation and 20 a non-disabled sibling. The children were questioned about
      their sibling relationship and their experiences of stress. The children with a
      sibling with autism also completed a questionnaire on their knowledge of the
      autistic syndrome. Analyses revealed that the three groups were basically similar
      in their ratings of the frequency of stressors involving their siblings. There
      was a trend for children with a disabled brother or sister to rate their
      relationship with the sibling more positively. Correlational analyses revealed an
      association between both stressor frequency and appraisal and the evaluation of
      the relationship with the brother or sister. Siblings of children with autism had
      a fair understanding of the autistic syndrome. In this group, there was also an
      association between the children's knowledge of the autistic disorder and the
      quality of the sibling relationship.

PMID- 8529294
TI  - Sibling empathy and behavioural adjustment of children with chronic illness.
AB  - This study investigated the relationship of healthy siblings' empathy to the
      psychosocial adjustment of children with a congenital heart disease (CHD) in 28
      sibling dyads aged 3.5-11 years, as well as the perceived quality of sibling
      interactions, reported by mothers and children with illness. As in previous
      studies, children with CHD were reported to have more behaviour problems in the
      clinical range than either siblings or normative populations. On the basis of a
      task unconnected with illness issues, siblings were assigned to a high or low
      empathy group. Children with illness, but not their mothers, saw the siblings
      with high empathy more positively than those with low empathy. However, the
      adjustment of the children with illness did not differ between high and low
      empathy groups. Findings suggest the need to seek children's points of view when
      studying psychosocial effects of paediatric conditions.

PMID- 8529295
TI  - The control of sexuality in young people with Down's syndrome.
AB  - Three studies were undertaken of two cohorts of young people with Down's
      syndrome. One cohort, of 52 people, was born in the 1960s and they were seen in
      their teens and again in their mid-20s. The other cohort, of 26 people, was born
      in the 1970s and they were seen in their teens. The studies show that while
      carers in both cohorts paid lip service to the rights of young people with
      learning disabilities to have sexual experiences and to marry, they did not
      necessarily feel that this applied to their own youngsters. Carers of the 1970s
      cohort at teenage were more permissive than carers of the 1960s cohort at
      adulthood. How carers controlled the sexuality of their young people is
      discussed. Carers in both cohorts were rarely in favour of parenthood for people
      with learning disabilities and over half the carers thought that sterilization
      might be appropriate, in some circumstances. At teenage, about two-thirds of
      carers in both cohorts thought that their youngsters needed sex education. By
      adulthood, in the 1960s cohort, only one-third of the same group of carers
      continued to hold the same view. According to carers, more young people knew
      about events that they were unlikely to experience themselves, namely pregnancy
      and birth, than knew about the most likely event, sexual intercourse. So, in
      spite of holding permissive views on sexual expression for people with learning
      disabilities, carers left their own young people ill-prepared for such
      experiences. Few young people were given the education or freedoms necessary to
      encourage sexual relationships. Reasons for this discrepancy are discussed.

PMID- 8529296
TI  - 'Sexuality, disability and abuse: advice for life ... not just for kids'!
AB  - This annotation addresses the debate about the availability, taboos, choices and
      risks concerning the sexuality and abuse of young disabled people. It highlights
      the vulnerability of some disabled young people and discusses the dilemmas of
      maintaining the disabled person's dignity, safeguarding his/her independence and
      recognizing the need for appropriate sex education while providing protection
      from abuse. It is suggested that statutory agencies as well as legislation should
      assume greater responsibility for protecting and safeguarding the interests of
      disabled youngsters, some of whom may risk physical, emotional and sexual abuse
      beyond childhood. The manner in which sexuality and abuse are dealt with often
      reflects the way disabled people are regarded by the society. This paper attempts
      to address some of the legal and conceptual issues surrounding this area.

PMID- 8529297
TI  - Further advances of chronic renal replacement therapy in eastern Germany, 1994
      versus 1989.
AB  - Unlike the other former Soviet-block countries, Eastern Germany/the "GDR", had
      the opportunity to the re-unification with a highly developed western country,
      the Federal Republic of (West) Germany in 1990. In order to record the following
      rapid improvements in renal replacement therapy, we performed our own survey in
      Eastern Germany--excluding Eastern Berlin--by questionnaire, comparing the years
      1989/December, and 1994/December. 112 of the 113 dialysis facilities for adult
      regular dialysis patients replied to our questionnaire (99%). From 1989 to 1994,
      the number of dialysis centers increased from 53 to 113 (-->213%), reaching 7.9
      centres p.m.p. Of these facilities, 29% were hospital centers, 48% were private
      dialysis units, and 23% were run by nonprofit dialysis organizations. The number
      of dialysis stations increased from 602 to 1,719 (-->286%), i.e. 120 stations
      p.m.p. The number of patients in regular dialysis treatment rose from 2,127 to
      5,335 (-->251%), that means a prevalence of 373 patients p.m.p. In 1989, 67 new
      patients (p.m.p.) had been accepted for maintenance treatment (incidence), in
      contrast to 130 new patients p.m.p. in 1994 (-->194%), now under the conditions
      of unlimited accessibility to dialysis treatment. Questions referring to this
      point--the incidence of new patients--were only asked in Thuringen (2.5 mio.
      inhabitants). Alternative treatment modalities became feasible under the new
      conditions in Eastern Germany. In contrast to 99% hemodialysis patients in
      December 1989, at the end of 1994 92.8% of the patients were treated by
      hemodialysis, 2.0% by hemofiltration, and 5.2% by peritoneal dialysis,
      predominantly CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529298
TI  - The Demers atrial catheter: experience with a single-lumen silicone catheter as
      short- and long-term access for hemodialysis.
AB  - The Demers catheter is a silicone atrial catheter with a dacron cuff used as
      short- and long-term access for hemodialysis. It was implanted in 316 patients
      between January 1, 1987 through May 31, 1991. Data on these implantations were
      retrospectively analyzed and are reported here. Follow-up and analysis was
      possible in 404 of 417 Demers catheter implantations. The mean age of patients in
      this study was 61 years. For short-term use (< 91 days) 153 catheters were
      implanted in 135 patients, for long-term use (> 90 days) 251 catheters in 181
      patients. The median life span of all 404 catheters was 87 days. The median life
      span for long-term use was 150 days (2-1302) per catheter and 220 days (92-1717)
      per patient. Catheter malfunction (arterial blood flow < 200 ml) was encountered
      every 876 days in the running time of the catheter. Twenty percent (n = 80) of
      the catheters were explanted because of complications. These included 42 cases of
      catheter malfunction and 22 cases of infection.

PMID- 8529299
TI  - Acute renal failure following massive mannitol infusion and enalapril treatment.
AB  - We report a patient with reversible acute oligoanuric renal failure. Intravenous
      mannitol 25% was infused to treat intracranial edema, during chronic
      administration of ACE inhibitors for arterial hypertension. Serum creatinine
      level rose to 5.6 mg/dl from a previous value of 1.2 mg/dl. Measured and
      calculated serum osmolalities were 310 and 280 mosm/kg respectively. We postulate
      that the association of afferent arteriolar constriction due to mannitol induced
      tubulo-glomerular imbalance and efferent dilatation due to ACE inhibitors
      provoked a sharp reduction in glomerular filtration rate. Alternatively, mannitol
      infusion may have caused tubular cell swelling with luminal obstruction.

PMID- 8529300
TI  - Hemodialyzability of sertraline.
AB  - Sertraline is an antidepressant which selectively inhibits the neuronal uptake of
      serotonin in the central nervous system. The pharmacokinetics of sertraline in
      end-stage renal disease (ESRD) and the effect of hemodialysis on sertraline
      clearance is unknown. A dose of 100 mg sertraline was administered to two anuric
      hemodialysis patients after hemodialysis. During the next hemodialysis session,
      simultaneous pre- and post dialyzer blood samples were obtained at the start of
      and hourly throughout dialysis until completion. All spent dialysate was
      collected hourly, quantified and an aliquot retained. Additional blood samples
      were obtained approximately 20 hours after dialysis and prior to the next
      treatment. Serum and dialysate were assayed for sertraline by gas chromatography
      mass spectroscopy. Initial sertraline serum concentrations were similar to those
      observed in subjects with normal renal function given the same sertraline dose,
      implying unaltered absorption and distribution. Sertraline was not detected in
      any dialysate sample. The elimination half-life was 42-92 h (normally 24-36 h),
      suggesting impaired clearance. Smaller doses of sertraline may be required in
      ESRD patients, yet post-hemodialysis supplementation is unnecessary.

PMID- 8529301
TI  - Adenocarcinoma at ureterosigmoidostomy junction in a renal transplant recipient
      15 years after conversion to ileal conduit.
AB  - In recent years, adenocarcinoma of the colon mucosa has become a recognized
      complication of ureterosigmoidostomy and in most cases the tumor arises at the
      site of ureterocolonic anastomosis. We report a case of a 29-year-old renal
      transplant recipient who developed two colonic carcinomas at the site of
      ureterosigmoidostomy 25 years after the urinary diversion and 15 years after
      conversion to an ileal conduit. This case emphasizes the need for a careful life
      long follow-up of all patients who undergo ureterosigmoidostomy.

PMID- 8529302
TI  - Hypouricemia with high urate clearance in hyponatremia: is it always a clue for
      increased effective volemia?

PMID- 8529303
TI  - Acute interstitial nephritis due to omeprazole.

PMID- 8529304
TI  - Renography in renovascular hypertension: four renal arteries.

PMID- 8529305
TI  - Availability of urinary mass screening in the detection of autosomal dominant
      polycystic kidney disease.

PMID- 8529306
TI  - IgA nephropathy associated with mild type-coagulation factor V deficiency in
      father and son.

PMID- 8529307
TI  - Contrast media induced irreversible acute renal failure in a patient treated with
      intraperitoneal cisplatin.

PMID- 8529308
TI  - Role of endothelin in malignant hypertension.

PMID- 8529309
TI  - Long-term follow-up of idiopathic membranous glomerulonephritis with its natural
      course.

PMID- 8529310
TI  - Focal and diffuse thin glomerular basement membrane in diabetes--morphologically
      distinct findings with different etiologies.

PMID- 8529311
TI  - Fine-needle aspiration-biopsy (FNAB) in immediate post-operative period of
      transplant. A valid support to discriminate acute rejection vs acute tubular
      necrosis.

PMID- 8529312
TI  - Anti-mesangial and anti-endothelial cell antibodies in IgA mesangial nephropathy.
AB  - In the present study we verified by solid phase ELISA the presence of antibodies
      against mesangial and endothelial cell constituents in patients with IgA-GN and
      Schoenlein-Henoch syndrome (SH). An antigen extract was prepared by sonication of
      human mesangial cell (MC) monolayers between third and fifth subculture and
      coated at 20 micrograms/ml on microtiter plates where sera were tested by
      incubation for 2 h at 37 degrees C and addition of peroxidase-conjugated anti
      human IgG or IgA. In comparison to 86 normal controls, increased levels of IgG
      anti-MC antibodies were found in 15/84 patients with IgA-GN and 4/11 with SH. IgA
      antibodies were always negative. Furthermore anti-endothelial cell antibodies
      (AECA) were sought in the same patients and controls by ELISA as previously
      described. Increased levels of IgG and IgA AECA were found in 25/62 and 24/46
      patients respectively. A cross-inhibition test showed that preadsorbment of
      positive sera for both IgG anti-MC and IgG AECA on endothelial cells in culture
      resulted in an inhibited binding of IgG to MC. HPLC-ELISA and Western blot
      analysis of the MC extract showed a significant binding of IgG from ELISA
      positive sera to a protein band of 25-50 kD. Similar results were obtained by
      Western blot analysis of an endothelial cell extract. These results suggest the
      identity of the antigens recognized by IgG antibodies on endothelial cells and MC
      in patients with IgA-GN.

PMID- 8529313
TI  - Polymorphism of the angiotensin converting enzyme gene and clinical aspects of
      IgA nephropathy.
AB  - To investigate the relationship between the insertion/deletion (I/D) polymorphism
      of the angiotensin converting enzyme (ACE) gene and the onset and progression of
      IgA nephropathy, we studied this polymorphism in 48 patients (21 males and 27
      females) with IgA nephropathy and 104 normal controls (51 males and 53 females)
      using the polymerase chain reaction method. There was no difference in either the
      genotype or allele frequency of the I/D polymorphism between the patients and
      normal controls (D allele frequency; 0.303 and 0.325, respectively). But, the
      mean slope of the reciprocal of the serum creatinine concentration was
      significantly steeper (p < 0.05) in the patients with the D allele (-0.0104 +/-
      0.007 dl.mg-1.month-1) than those without the D allele (-0.0055 +/- 0.008 dl.mg
      1.month-1). The mean percentage of the glomeruli with sclerosis or segmental
      lesions obtained from each renal biopsy specimen was significantly larger (p <
      0.02) in the patients with the D allele (49.5 +/- 17.8%) than in those without
      (33.3 +/- 22.9%). These results suggest that 1. the ACE gene polymorphism is not
      related to the onset of IgA nephropathy, but 2. the progression of IgA
      nephropathy may be influenced by the polymorphism which may be involved in
      glomerular hypertension.

PMID- 8529314
TI  - Serum immunoglobulin E in primary IgA nephropathy.
AB  - The biosynthesis of human immunoglobulin E (IgE) is regulated by a complex
      network involving T and B lymphocytes. Diseases associated with high serum IgE
      (sIgE) levels are usually characterized by T cell disorders. Total sIgE level has
      been found to be of clinical relevance in minimal change nephrotic syndrome.
      However, the clinical significance has rarely been studied in primary IgA
      nephropathy (IgA N). We retrospectively studied 99 cases of primary IgA N. There
      were 59 males and 40 females with a mean age of 30.0 +/- 12.1 years. The mean
      follow-up duration was 45.9 +/- 31.1 months. Pathological grading was done
      according to the criteria of Meadow et al. Median sIgE for the entire group was
      122.0 IU/ml (range: 2.8-5805 IU/ml) which was significantly higher than the
      healthy control group (median: 43,7 IU/ml, range: 5.0-1003 IU/ml, p < 0.001).
      However, when the IgA N cases were stratified into grades, only grade I (median:
      514 IU/ml, range: 72.1-5805.0 IU/ml) and grade II (median: 229 IU/ml, range: 5.0
      5464 IU/ml) patients had significantly higher sIgE than the control group (p <
      0.0005 and p < 0.001 respectively). Patients with nephrotic ranged proteinuria
      (32 cases) were further classified into "stable" and "progressive" groups. The
      "stable" group had a significantly higher sIgE level (median: 922.0 IU/ml, range:
      2.8-5805 IU/ml), compared to that of the "progressive" group (median: 55.3 IU/ml,
      range: 5.0-1600 IU/ml, p < 0.02). The effect of aggressive treatment (including
      corticosteroid and/or cyclophosphamide, cyclosporine) was also assessed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8529315
TI  - Significance of urinary fibrin/fibrinogen degradation products (FDP) D-dimer
      measured by a highly sensitive ELISA method with a new monoclonal antibody (D-D
      E72) in various renal diseases.
AB  - To diagnose the abnormalities of coagulation-fibrinolysis in various renal
      diseases, we developed a new monoclonal antibody (D-D E72) against
      fibrin/fibrinogen degradation products D-dimer (FDP D-dimer) and established a
      highly sensitive enzyme-linked immunosorbent assay (ELISA) for its measurement.
      FDP D-dimer was assessed in 102 patients with various renal diseases, and the
      following results were obtained: 1. The mean level of urinary FPD D-dimer in 32
      normal controls was 0.69 +/- 0.60 ng/ml (mean +/- SD). 2. The level of urinary
      FDP D-dimer was significantly higher in primary nephrotic syndrome group (NS),
      chronic renal failure group (CRF) and in the group of diabetic nephropathy (DM)
      than in the control group. However, no difference was observed in the level of
      urinary FDP D-dimer between non-nephrotic chronic glomerulonephritis group (CGN)
      and control group. 3. No significant correlation was revealed between D-dimer and
      urinary protein in CGN and NS groups. These results suggest that in addition to
      plasma filtration the urinary FDP D-dimer in NS, CRF and DM may be also related
      to abnormalities of secondary fibrinolysis in intra-glomerular fibrin deposits.

PMID- 8529316
TI  - Clinical features of 24 patients on regular hemodialysis treatment (RDT) for 16
      23 years in a single unit.
AB  - Careful investigation of the clinical conditions of patients on maintenance
      hemodialysis for about 20 years in a single dialysis unit was of great interest
      for evaluation of the pathological consequences in long-term survivors of
      insufficient correction of uremia and of the dialysis treatment "per se". We
      analyzed the outcomes for a cohort of 116 patients who started RDT before 1976
      and the clinical conditions of the 24 patients still on RDT in our unit at the
      end of 1991 (average duration of treatment = 222 +/- 23 months). Actuarial
      survival was 72% at 10 years and 43% at 20 years. Rehabilitation of the 24
      survivors was rather good: 13 were able to work, 8 were retired or unable to
      work, but able to care for most personal needs. Actual body weight,
      anthropometric parameters and biochemical parameters revealed a well-preserved
      nutritional status. Anemia improved from 23 +/- 7 at the start of RDT to 31 +/- 8
      in the 21 patients never treated with erythropoietin. Blood pressure was normal
      without therapy in 18 patients and elevated in 6. Mild-to-moderate left
      ventricular hypertrophy was present in all the 6 patients with arterial
      hypertension and in only 6 of the 18 normotensive patients. The ratio of early
      diastolic filling to filling during atrial contraction (E/A ratio) was < 1 in 16
      patients: it was 1.05 +/- 0.43 in 9 patients with stable intradialysis blood
      pressure and significantly lower (0.73 +/- 0.15) in 12 patients with recurrent
      intradialysis hypotension. Supraventricular arrhythmias were detected by Holter
      monitoring in 41% and ventricular arrhythmias in 35% of patients. Extensive
      vascular calcifications were present (in 100% of patients in the abdominal
      aorta), but only 4 patients showed clinical signs of peripheral vascular disease.
      Subperiosteal resorption was detected radiologically in the hands of 59% of
      patients. Bone histology, interpretable for only 20 patients, revealed no bone
      lesions in 1 case (5%), mild mixed osteodystrophy in 3 cases (15%), advanced
      mixed osteodystrophy in 5 cases (25%), osteodystrophy with predominant
      hyperparathyroidism in 2 cases (10%), osteodystrophy with predominant
      osteomalacia in 6 cases (30%), and aplastic bone disease in 3 cases (15%).
      Moderate aluminum staining was found in only 4 patients and was more marked in
      earlier biopsies taken before withdrawal of the aluminium-containing phosphate
      binding drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8529317
TI  - Variability in leukocyte subset measurements among five laboratories in
      Vancouver.
AB  - Cell counts and percentages of CD4 are widely used in the prognostic and clinical
      management of HIV-infected patients, and as surrogate outcomes in clinical trials
      involving HIV-infected individuals. Considerable variability in CD4 counts has
      been documented due to physiologic and methodologic factors. While studies of
      variability of CD4 counts among American and French laboratories have been
      reported in the literature, no published data are available for Canadian
      laboratories. This paper describes the results of a study to determine the
      variability of leukocyte subsets among 5 laboratories in Vancouver, British
      Columbia. Samples were collected in a prospective fashion from 52 HIV-negative
      patients from July 1991 to November 1993. Coefficients of variation (CV) were
      calculated for leukocyte subset percentages and absolute cell counts among
      laboratories. Our results demonstrate that the variability in leukocyte subsets
      among 5 Vancouver laboratories was lower than or comparable with published
      findings. The variability remained stable over the time period of the study,
      although 4 of the 5 laboratories participated in quality assurance programs. This
      suggests a plateau in the impact of this program. Since the variability among
      laboratories is less than the variability attributable to physiologic factors,
      further research efforts to reduce this variability should focus on physiologic
      sources.

PMID- 8529318
TI  - Small bowel permeability--a variable effect of NSAIDS.
AB  - The baseline permeability of small bowel in 57 healthy volunteers was assessed by
      measuring the mannitol and chromium-EDTA recovery in a 5-hour urine collection
      after ingestion of a drink containing a mixture of 1 g of mannitol and 3.7 MBq of
      51Cr-EDTA. Subjects were treated with medication for 1 week followed by
      permeability studies as described above. The regimens used were diclofenac sodium
      (Voltaren) 50 mg po tid (21 subjects), Voltaren SR 75 mg bid for 1 week (34
      subjects), indomethacin 50 mg tid (10 subjects), and tenoxicam (Mobiflex) 20 mg
      daily (13 subjects). There was no significant difference between the mannitol
      recoveries at baseline or after any of the drugs. The permeability was clearly
      increased by indomethacin and by Voltaren SR. Conventional-release Voltaren
      increased permeability, but the results were not significantly above baseline.
      Mobiflex had no influence on the measured permeability. Our results suggest that
      the SR preparation of diclofenac has a more pronounced effect than regular
      diclofenac sodium; thus different NSAIDs and different preparations of the same
      NSAID may have different effects on small bowel permeability.

PMID- 8529319
TI  - Novel low-dosage hormonal replacement therapy complements dietary treatment of
      moderately hypercholesterolemic postmenopausal women.
AB  - It is not known whether female hormonal replacement therapy (HRT) influences
      fasting plasma lipoprotein lipids in diet-treated hypercholesterolemic subjects.
      Thirteen moderately hypercholesterolemic postmenopausal women were studied during
      dietary treatment alone with a low fat, low cholesterol diet for the 3 months and
      during the subsequent 2 y of HRT with dl-norgestrel (0.075 mg daily) and
      estradiol-17 beta (1 mg, 25 of 28 days) with maintenance of the same diet.
      Hormonal replacement therapy decreased plasma total cholesterol by 11 +/- 3% (5.7
      vs. 6.4 mmol/L, p < 0.005), due to a 17 +/- 3% mean reduction (p < 0.001) in the
      concentration of plasma low density lipoprotein cholesterol (3.9 vs. 4.7 mmol/L,
      p < 0.001). The ratio of plasma total cholesterol to high density lipoprotein
      cholesterol fell significantly by 17 +/- 4% (4.1 vs. 4.9, p < 0.005). Mean
      fasting plasma concentrations of total triglycerides (1.1 vs. 1.6 mmol/L, p <
      0.005) fell by 31 +/- 6%, and very low density lipoprotein triglycerides (0.56
      vs. 0.83 mmol/L, p < 0.02) by 33 +/- 9%. Hormonal replacement therapy was well
      tolerated, improved mood levels, and increased the mineral content of the
      vertebral spine significantly, while effectively relieving vasomotor flushing.
      Hormonal replacement therapy complements the dietary treatment of
      hypercholesterolemia.

PMID- 8529320
TI  - Applied recording force and noninvasive arterial pulses.
AB  - Arterial pressure pulses are often measured noninvasively, but the influence of
      external recording forces has not been well documented. Accordingly, the main
      goal was to delineate pulse contour and amplitude distortion with progressively
      compressive forces applied to an external transducer. Ten young normal male
      subjects were studied while supine. Pulses were recorded at the end of a normal
      expiration over a range of forces (0.45-4.29, 0.42N increments) applied in a
      randomized order over first the brachial and then the radial artery. Pulse
      contours were Fourier analyzed and harmonic powers were normalized to the peak
      power at the fundamental frequency. Brachial artery pulse amplitudes
      progressively decreased (p = 0.013), whereas, those at the radial artery peaked
      at a recording force of 1.79 +/- 0.01N (p < 0.001) and subsequently decreased
      parallel to the brachial data with larger forces. No significant pulse contour
      distortions occurred at either the brachial or radial artery with applied forces
      of up to 2.18 +/- 0.02 and 2.59 +/- 0.02N, respectively, as indicated by the
      similarity of the relative power for harmonics 2-7. Radial artery pulses were
      distorted at and beyond a force of 2.99 +/- 0.01N as indicated by the increased
      relative power of harmonics 3-7 (p < 0.05). Therefore, despite significant
      alterations in pulse amplitude, the relative shape of pulses remains similar over
      a large range of lower recording forces.

PMID- 8529321
TI  - Role of a brush border membrane fatty acid binding protein in oleic acid uptake
      into rat and rabbit jejunal brush border membrane.
AB  - Oleic acid uptake was studied using adult rat and rabbit jejunal brush border
      membrane vesicles. The intestinal uptake of oleic acid is influenced by the
      activity of an amiloride-inhibitable brush border membrane Na+/H+ exchanger,
      NHE3: opposing Na+/H+ gradients (inward Na+ and outward H+ gradients) increased
      oleic acid uptake by about 40%, as compared with only an inward Na+ gradient,
      only an outward H+ gradient, or the absence of either Na+ or H+ gradients. This
      study was undertaken to test the hypothesis that a portion of oleic acid uptake
      is facilitated by a fatty acid binding protein in the brush border membrane
      (FABPPM) of adult rat jejunum. There was a reduction in the uptake of oleic acid
      when brush border membrane vesicles were incubated with a rat liver plasma
      membrane fatty acid binding protein antibody (anti-FABPPM-Ab) in the absence, but
      not in the presence, of opposing Na+/H+ gradients. Thus, oleic acid uptake occurs
      largely by partitioning of the lipid into the brush border membrane, as well as
      by a process which involves the activation of the brush border membrane Na+/H+
      exchanger, and a membrane fatty acid binding protein.

PMID- 8529322
TI  - A marked and sustained reduction in LDL sterols by diet and cholestyramine in
      beta-sitosterolemia.
AB  - This study examines the therapeutic outcome of a low plant sterol diet and
      adjunctive drug therapy (cholestyramine) in the long term treatment of beta
      sitosterolemia. A diet restricted in plant sterols, cholesterol and fat was
      implemented in a 48-year-old male beta-sitosterolemic patient. The plant sterols
      beta-sitosterol, campesterol and stigmasterol, and cholesterol content of the
      diet were quantitated by a gas chromatography method (GLC) during metabolic ward
      studies. Food table analysis of dietary sterols, while quantitatively similar to
      GLC, significantly underestimated the level of plant sterols and therefore
      overestimated dietary cholesterol intake. The duration of the study was 18
      months. The effect of the diet over a period of 6 months on the sterol levels of
      plasma and individual lipoprotein fractions (VLDL, LDL, HDL) was evaluated.
      Apolipoproteins A-1 and B-100 levels were measured. The same parameters were
      assessed over the next 12 months with the adjunctive use of cholestyramine and
      dietary restrictions. The diet was effective in lowering total, VLDL, and LDL
      plant sterols by 37%, 59%, and 32% respectively. The low plant sterol diet did
      not change total plasma, VLDL or LDL cholesterol. With the addition of
      cholestyramine, total plasma and LDL cholesterol declined by 64 and 76%,
      respectively, while HDL-cholesterol remained unchanged. LDL plant sterols
      declined by 77%, while VLDL plant sterol showed no further change. The decline
      showed no discrimination among the individual plant sterols. One week after
      cholestyramine therapy, apolipoprotein B fell from 1.03 to 0.11 g/L, while
      apolipoprotein A rose from 1.29 to 1.79 g/L. These levels subsequently stabilized
      at 70% below (0.29 g/L) and 42% above (1.81 g/L) that of diet therapy alone.
      Xanthomas, angina pectoris, and intermittent claudication resolved during the
      diet and cholestyramine therapy period. Dietary restriction of plant sterols
      combined with cholestyramine therapy is an effective means of treating beta
      sitosterolemia.

PMID- 8529324
TI  - Assisted suicide: opinions of Alberta physicians.
AB  - The legal status of assisted suicide and active euthanasia are receiving
      increasing attention among physicians, legislators, the judiciary, and public
      lobby groups. Many seem to assume that these forms of assisted dying reside
      naturally within the practice of medicine but, surprisingly, comprehensive data
      about the opinions of Canadian physicians are not available. We report the
      results of a survey of the opinions of Alberta physicians about assisted suicide,
      compare their opinions to those about active euthanasia, and determine their
      relationships with various demographic and bioethical matters. A stratified
      random sample (n = 2,002) was drawn from all Alberta physicians. The response
      rate was 69% (1,391) and was representative of the reference population for age,
      sex, and type of practice. Fifty-five percent believed assisted suicide should
      remain a criminal offence, whereas 18% did not, and 27% were uncertain. Strong
      relationships were found between opinions about assisted suicide, and age and
      religious activity. These data demonstrate no ground swell of support by Alberta
      physicians for the decriminalization of assisted suicide. Our data confirm the
      need for a national study of the opinions of Canadian physicians about physician
      assisted dying, and caution against precipitate changes in relevant legislation
      and health policy.

PMID- 8529323
TI  - Challenging consults: application of principles of physiology and biochemistry to
      the bedside. Osmotic diuresis: the importance of counting the number of osmoles
      excreted.
AB  - Polyuria is usually the result of a water diuresis or an osmotic diuresis.
      Traditionally, the assessment of the extracellular fluid (ECF) volume and the
      concentration of Na+ in plasma is sufficient to differentiate between the two. We
      present a case and our approach, which is based on calculations and quantitation
      of osmoles, to demonstrate the utility of this approach. A patient with diabetes
      mellitus, human T-cell lymphocyte virus, type 1 (HTLV-1) associated lymphoma, and
      hypercalcemia presented with marked ECF volume contraction and polyuria. A spot
      urine osmolality was 567 mOsm/kg H2O in the face of urine output of approximately
      6 L/d. The initial diagnosis was an osmotic diuresis. However, a quantitative
      analysis revealed the enormous number of osmoles could not be accounted for
      physiologically. Hence, we postulated a water diuresis to be the cause of the
      polyuria. To confirm this hypothesis, we found that at different times during his
      hospitalization, the urine specific gravity ranged from 1.005 to 1.022, and urine
      output varied markedly over 8-h periods. Despite a plasma sodium of 147 mmol/L,
      the patient did not complain of thirst. Taken together, this suggested the
      presence of a hypothalamic lesion which caused central diabetes insipidus with
      variable output of antidiuretic hormone together with a blunted thirst response.
      Illustration of the utility of a quantitative approach to polyuria is the focus
      of the discussion.

PMID- 8529325
TI  - Meta-analysis: a method for synthesizing research.

PMID- 8529326
TI  - Itraconazole and hydroxyitraconazole serum concentrations are reduced more than
      tenfold by phenytoin.
AB  - OBJECTIVE: To study the disposition of single doses of phenytoin and itraconazole
      when administered alone and after chronic treatment with the other drug. METHODS:
      Healthy male volunteers were randomized to two groups and studied in parallel. In
      group 1, a single 200 mg oral dose of itraconazole was administered on two
      occasions (alone and after 15 days of 300 mg oral phenytoin once daily). Subjects
      in group 2 were given a single 300 mg oral dose of phenytoin before and after 15
      days of itraconazole (200 mg once daily). Blood was collected for 96 hours after
      each single dose of phenytoin or itraconazole. Serum was assayed for itraconazole
      and hydroxyitraconazole concentration by HPLC and for phenytoin concentration by
      fluorescence polarization immunoassay. RESULTS: Phenytoin decreased the area
      under the concentration-time curve (AUC) of itraconazole by more than 90%, from
      3203 to 224 ng.hr/ml, accompanied by a decrease in half-life from 22.3 to 3.8
      hours. Similar changes were observed for hydroxyitraconazole AUC (decreased from
      6224 to 315 ng.hr/ml) and half-life (11.3 versus 2.9 hours). Itraconazole
      increased the AUC of phenytoin (10.3%; p < 0.05), with no change in any other
      pharmacokinetic parameter. CONCLUSIONS: The striking decrease in itraconazole
      concentrations with phenytoin is due to induction of metabolism combined with a
      reduction in the degree of saturable metabolism normally exhibited by
      itraconazole at this dose. The magnitude of interaction likely accounts for
      reports of therapeutic failures in patients with fungal infections who are
      receiving both itraconazole and phenytoin.

PMID- 8529327
TI  - Comparative effects of omeprazole on xenobiotic metabolizing enzymes in the rat
      and human.
AB  - Omeprazole induces CYP1A in the human liver and gut, which has led to concern
      about possible side effects. The purpose of this study was to compare the effects
      of omeprazole on phase 1 and phase 2 enzymes in the rat and human. Male rats were
      treated with intraperitoneal (40 or 80 mg/kg) or oral omeprazole (40 mg/kg) for 5
      or 14 days, respectively. The activities and amounts of CYP1A, uridine
      diphosphate-glucuronosyltransferase, and glutathione transferase were determined
      in liver and gut. Enzyme activities were also determined in duodenal biopsy
      specimens from six healthy human volunteers before and after treatment with
      omeprazole (20 mg/day) for 10 days. Treatment with intraperitoneal omeprazole (40
      mg/kg; 80 mg/kg) coinduced uridine diphosphate-glucuronosyltransferase (36%;
      66%), glutathione transferase (22%; 50%), and CYP1A (26%; 50%) in rat liver. In
      rat small intestine, comparable levels of induction were observed for uridine
      diphosphate-glucuronosyltransferase and glutathione transferase; CYP1A was
      unaffected. Oral omeprazole had similar effects. Immunoblotting showed
      corresponding changes in the amounts of these enzymes. Omeprazole increased the
      activities of CYP1A (19% to 167%; p = 0.014) and uridine diphosphate
      glucuronosyltransferase (11% to 68%; p = 0.04) in the duodenal biopsy specimens
      of all six human volunteers; glutathione transferase was unaffected. Thus,
      omeprazole coinduced multiple xenobiotic metabolizing enzymes in the rat and
      human. The pattern of induction differed in the rat and human, consistent with
      known differences in genetic regulatory elements in the two species.

PMID- 8529328
TI  - Tolrestat pharmacokinetic and pharmacodynamic effects on red blood cell sorbitol
      levels in normal volunteers and in patients with insulin-dependent diabetes.
AB  - OBJECTIVES: To examine the effect of diabetes mellitus on the pharmacokinetics of
      tolrestat and to investigate its effect on red blood cell sorbitol levels
      according to a new pharmacodynamic model for this class of drugs. METHODS: Single
      and multiple doses of tolrestat (200 mg/twice a day) were administered to 12
      patients with insulin-dependent (type I) diabetes and 12 healthy volunteers in an
      open parallel trial. RESULTS: Tolrestat disposition was characterized by first
      order absorption and biexponential disposition: In normal subjects the terminal
      disposition half-life (t1/2) was 13 +/- 3 hours (mean +/- SD) and the apparent
      oral clearance (CL/F) was 48 +/- 9 ml/hr/kg, similar to the values in patients
      with type I diabetes mellitus (t1/2 = 14 +/- 4 hours; CL/F = 55 +/- 10 ml/hr/kg).
      Red blood cell sorbitol concentrations, which declined because of tolrestat's
      inhibition of aldose reductase, were characterized by an indirect-response model
      including a 50% inhibition constant (IC50) for production of sorbitol by aldose
      reductase. The removal of sorbitol (kout) was slower in patients with diabetes.
      The plasma IC50 averaged 2.0 +/- 1.3 micrograms/ml in normal subjects and 2.5 +/-
      1.9 micrograms/ml in patients with diabetes. IC50 values expressed in free
      (unbound) concentrations (fu = 0.64%), which ranged from 12 to 16 ng/ml, were
      similar to the in vitro IC50 for inhibition of sorbitol accumulation in human red
      blood cells. CONCLUSIONS: Tolrestat pharmacokinetics were similar in normal
      subjects and in patients with diabetes; however, the patients with diabetes had
      higher baseline sorbitol levels (11 versus 5 nmol/ml for normal subjects) and
      slower sorbitol efflux rates. The proposed biochemically realistic, dynamic model
      characterized well the red blood cell sorbitol response patterns after
      administration of single and multiple doses of tolrestat.

PMID- 8529329
TI  - Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its
      active metabolite EXP3174 in humans.
AB  - The pharmacokinetics of the angiotensin II receptor antagonist losartan potassium
      and its active carboxylic acid metabolite EXP3174 were characterized in 18
      healthy male subjects after administration of intravenous losartan, intravenous
      EXP3174, and oral losartan. In these subjects, the average plasma clearance of
      losartan was 610 ml/min, and the volume of distribution was 34 L. Renal clearance
      (70 ml/min) accounted for 12% of plasma clearance. Terminal half-life was 2.1
      hours. In contrast, the average plasma clearance of EXP3174 was 47 ml/min, and
      its volume of distribution was 10 L. Renal clearance was 26 ml/min, which
      accounted for 55% of plasma clearance; terminal half-life was 6.3 hours. After
      oral administration of losartan, peak concentrations of losartan were reached in
      1 hour. Peak concentrations of EXP3174 were reached in 3 1/2 hours. The area
      under the plasma concentration-time curve of EXP3174 was about four times that of
      losartan. The oral bioavailability of losartan tablets was 33%. The low
      bioavailability was mainly attributable to first-pass metabolism. After
      intravenous or oral administration of losartan the conversion of losartan to the
      metabolite EXP3174 was 14%.

PMID- 8529330
TI  - Ceftazidime pharmacokinetics in preterm infants: effects of renal function and
      gestational age.
AB  - OBJECTIVE: The objectives of this study were (1) to determine the effects of
      gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to
      relate these effects to changes in glomerular filtration rate (GFR), and (3) to
      establish appropriate dosage recommendations for preterm infants on day 3 of
      life. METHODS: Multiple-dose pharmacokinetics of ceftazidime (administered twice
      daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136
      preterm infants on day 3 of life. Blood samples were collected from an arterial
      catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC
      method was used to determine ceftazidime concentrations in serum. The GFR was
      studied simultaneously by means of the 24-hour continuous inulin infusion
      technique. RESULTS: The total body clearance, volume of distribution, and
      elimination serum half-life of ceftazidime (mean +/- SD) were 55.7 +/- 34.4 ml/hr
      (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (350 +/- 96 ml/kg), and 6.95 +/- 2.32
      hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4
      and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L.
      Clearance and volume of distribution of ceftazidime and GFR increased
      significantly with increasing gestational age, whereas serum trough levels and
      serum half-life of ceftazidime decreased significantly with increasing
      gestational age. Ceftazidime clearance increased significantly with increasing
      GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values
      and ceftazidime clearances. CONCLUSIONS: Dosage recommendations for ceftazidime
      administration in preterm infants during the first week of life should be based
      on gestational age and GFR. Additional adjustments in dosage are indicated in
      preterm infants who are exposed prenatally to indomethacin.

PMID- 8529331
TI  - Fosinopril: pharmacokinetics and pharmacodynamics in congestive heart failure.
AB  - Fosinoprilat, the active product of fosinopril, is eliminated by a hepatic
      pathway, in addition to the renal pathway shared by other angiotensin converting
      enzyme inhibitors. Congestive heart failure (CHF) may elevate drug plasma
      concentrations caused by a reduction in steady-state volume of distribution (Vss)
      and/or an impairment of clearance. This study compared the pharmacokinetics and
      pharmacodynamics of fosinopril (intravenous and oral) in 10 patients with
      established CHF and 10 age-, sex-, and weight-matched normal control subjects.
      There were no statistically significant differences between the patients with CHF
      and the control patients with respect to maximum drug concentration (Cmax) or
      area under the plasma concentration-time curve from 0 to infinity. Absolute
      bioavailability was approximately 29%. Vss was similar, and protein binding was
      99% in both groups. The oral half-life of fosinoprilat was significantly longer
      than the intravenous half-life for both the patients with CHF and normal
      subjects, without statistically significant differences between the study groups.
      Median time to reach Cmax occurred at 4 hours in each group and corresponded to
      maximum angiotensin converting enzyme inhibition, which was essentially complete
      through 12 hours and markedly reduced through 24 hours. Thus these data indicate
      that patients with CHF can receive fosinopril without undue increases in
      fosinoprilat concentrations. This probably is due to the dual excretory pathways.

PMID- 8529332
TI  - Topographic electroencephalogram of propofol-induced conscious sedation.
AB  - OBJECTIVES: To determine the effects of increasing doses of propofol that induce
      conscious sedation on the topographic electroencephalogram (EEG) of human
      volunteers and to test the hypothesis that more frontal brain areas are affected
      by low doses of propofol. METHODS: The scalp EEG was recorded monopolarly from 16
      different sites based on the 10-20 International System. Microcomputer-based
      hardware and RHYTHM 7.1 software were used to obtain quantitative power frequency
      topographic EEG data. A total of 10 normal adult volunteers were given
      incremental doses of propofol targeted to plasma concentrations of 0 to 1200
      ng/ml. RESULTS: Sedative concentrations of propofol produced a dramatic increase
      in beta 1, an increase in alpha 2 and beta 2, and an increase in delta activity
      at the largest concentration, with almost no change in theta activity. The
      increase in beta 1 activity had a linear correlation with plasma propofol levels
      (r = 0.9). Topographic mapping indicated that beta 1 activation was primarily in
      the frontal and central regions, with focal changes more in the left hemisphere.
      CONCLUSIONS: Topographic brain EEG mapping techniques indicate that frontal brain
      beta 1 EEG activity may be useful as an objective brain index of propofol
      conscious sedation.

PMID- 8529333
TI  - Neuropeptide Y in human hand veins: pharmacologic characterization and
      interaction with cyclic guanosine monophosphate-dependent venodilators in vivo.
AB  - The dorsal hand vein compliance technique was used to study direct vascular
      effects of human neuropeptide Y in vivo. Human neuropeptide Y is an endogenous
      vasoconstrictor peptide that is costored with norepinephrine in sympathetic nerve
      endings and coreleased with the catecholamine under various physiologic and
      pathologic conditions. Compared with the alpha 1-adrenergic agonist phenylephrine
      (geometric mean dose-rate that produces the half-maximal response [ED50]: 1.05
      nmol/min; maximum venoconstriction [Emax] +/- SEM, expressed as a percentage of
      baseline compliance: 91% +/- 3%), human neuropeptide Y was nine times more potent
      (geometric mean ED50: 0.122 nmol/min; p < 0.001) but markedly less efficacious
      (Emax: 58% +/- 4%; n = 12; p < 0.001). Venoconstrictor effects of human
      neuropeptide Y lasted several hours and were unchanged by simultaneous
      administration of alpha-adrenergic antagonists but were readily reversed by
      nitroglycerin or bradykinin. The high responsiveness of subcutaneous veins to
      human neuropeptide Y indicates that human neuropeptide Y may regulate venous
      compliance and filling of the venous subcutaneous capacitance bed in vivo.

PMID- 8529334
TI  - Sympathomimetic effects of paraxanthine and caffeine in humans.
AB  - Caffeine is metabolized extensively (on average 80%) to paraxanthine. With
      regular caffeine consumption, average serum levels of paraxanthine are two thirds
      those of caffeine. Both caffeine and paraxanthine competitively and
      nonselectively inhibit adenosine receptors in vitro. To examine the contribution
      of paraxanthine to the pharmacologic activity of caffeine, we administered to 12
      subjects in a crossover design oral caffeine (2 or 4 mg/kg) versus placebo or
      oral paraxanthine (same dose as caffeine) versus placebo, each after 3 days of
      methylxanthine abstinence. Both caffeine and paraxanthine significantly increased
      diastolic blood pressure, plasma epinephrine levels, and free fatty acids.
      Caffeine and paraxanthine produced a similar magnitude of response at 4 mg/kg;
      however, caffeine appeared to produce greater responses than paraxanthine at 2
      mg/kg. Caffeine and paraxanthine have similar sympathomimetic actions. The
      activity of paraxanthine needs to be considered in understanding the clinical
      pharmacology of caffeine, particularly with chronic, repetitive caffeine
      consumption.

PMID- 8529335
TI  - Comparison of the Bayesian approach and a simple algorithm for assessment of
      adverse drug events.
AB  - The differential diagnosis of severe adverse drug events can be based on clinical
      judgment, algorithms, or the Bayesian approach. The Bayesian Adverse Reactions
      Diagnostic Instrument (BARDI) calculates the posterior probability (PsP) in favor
      of a specific drug cause based on background (e.g., epidemiologic) and case
      information (e.g., time of onset). Although BARDI discriminates between drug- and
      nondrug-induced adverse events, its apparent complexity may limit its use. BARDI
      results were compared with those from an algorithm for rating the probability
      that an adverse drug event is drug-induced (Adverse Drug Reaction Probability
      Scale, or APS) that is still commonly used. APS scores were obtained by two
      independent raters for 106 challenging cases that had been analyzed from 1 to 5
      years ago with BARDI (91 cases of hypersensitivity, 12 cases of hematologic
      toxicity, and three cases of pulmonary toxicity); 130 ratings were generated
      because of the use of multiple drugs. APS scores for the two raters were highly
      correlated (r = 0.79; p < 0.0001). Probabilities of drug causation with use of
      BARDI versus average APS scores were significantly correlated (rs = 0.45; p <
      0.0001). However, BARDI better distinguished cases that were highly probable (n =
      83; PsP > or = 0.75) or highly improbable (n = 30; PsP < or = 0.25), whereas the
      APS rated the majority of these cases in the midrange (n = 128; range of APS, 1
      to 8.9). These results suggest that APS and BARDI evaluations are concordant.
      Thus the APS may be an effective screening tool, although BARDI can better
      discriminate drug from nondrug-induced cases and may be more appropriate for
      serious cases of adverse drug reactions.

PMID- 8529336
TI  - Stability of Dental Anxiety Scale scores: a longitudinal study of older adults.

PMID- 8529337
TI  - Dental caries in Namibia--the first national survey.

PMID- 8529338
TI  - Dental caries among children from Solntsevsky--a district in Moscow, 1993.

PMID- 8529339
TI  - Restoration of approximal carious lesions--application of decision analysis.

PMID- 8529340
TI  - Social and behavioural indicators of caries experience in 5-year-old children.

PMID- 8529341
TI  - Retention and caries preventive effects of a GIC and a resin-based fissure
      sealant.

PMID- 8529342
TI  - Subjective and objective orthodontic treatment need among orthodontically treated
      and untreated Finnish adolescents.

PMID- 8529344
TI  - Loss to follow-up in a longitudinal oral health survey of older adults.

PMID- 8529343
TI  - Incidence of attachment loss over 3 years in older adults--new and progressing
      lesions.

PMID- 8529345
TI  - Jaw function status in an elderly community sample.

PMID- 8529346
TI  - Water fluoridation, bone density and hip fractures: a review of recent
      literature.

PMID- 8529347
TI  - Mutans streptococci and dental caries in schoolchildren in southern Thailand.

PMID- 8529348
TI  - Periodontal condition and comparison of toothcleaning using chewing sponge,
      chewing sticks and toothbrushes in 14-year-old schoolchildren in Ghana.

PMID- 8529349
TI  - Developing interactive computer-based simulations: an object-oriented development
      methodology enhances computer-assisted instruction.
AB  - The purpose of this research was to investigate the application of object
      oriented technology and AI techniques to enhance development of computer-based
      training simulations. Towards that end, a comprehensive computer-assisted
      instructional unit was developed to teach the skills and concepts of window-based
      applications, the OS/2 desktop, and the use of a patient care information system.
      By taking advantage of sophisticated computer graphics for the visual
      representation of objects and the behavioral modeling capabilities of the object
      oriented language, domain knowledge modeling and human-computer interactions were
      implemented without complex natural language processing techniques. The results
      of this research indicate that nurses and physicians are able to learn the basic
      skills and concepts of computer systems and how to query for patient information.
      The new methodology described for building these computer-assisted instructional
      simulations significantly eased the training and teaching of large numbers of
      nurses and physicians and simplified their transition to a complex, computer
      based hospital information system environment.

PMID- 8529350
TI  - Considering imperfections using 3D imaging system in angle obtaining, angle
      signal distance computing and multivariate distance graphing.
AB  - Fields such as medicine, biomechanics or ergonomics need to measure the positions
      and the rotational movements of body segments. The aim of this article is to
      underscore the problem of imperfection on angle measurement using a three
      dimensional television system. First, the error on a single angle value is
      assessed through the classical Taylor's formula and through a simulating
      approach. Then the error is considered for an entire signal through either an
      experimental design or a simulating approach. To take into account such an error
      when comparing two angle multidimensional signals, a specific coding technique is
      suggested. Finally, two graphical patterns are proposed to show globally the
      distance between the signals with regard to the error.

PMID- 8529351
TI  - A computer program for automatic measurement of respiratory mechanics in
      artificially ventilated patients.
AB  - A program for automatic and periodic determination of respiratory mechanics in
      artificially ventilated patients is described. Airway pressure and flow signals
      are obtained from the ventilator in the controlled ventilation mode with constant
      flow inflation and end-inspiratory pause. Periodically, the program records both
      signals for a given time and it delimits a ventilatory cycle and its components
      out of this record. Then, four mechanical parameters of the respiratory system
      are calculated: (1) Rinit, the resistance obtained with the end-inflation
      occlusion technique; (2) Ers, the elastance (inspiratory) calculated from the
      slope of the airway pressure profile during inflation; (3) tau, the expiratory
      time constant; (4) PEEP, the global positive end expiratory pressure. All
      parameter measurements have been evaluated in experimental conditions, and are in
      good agreement with reference values. The complete software includes the display
      of the signals and of the trends together with automatic disk file backups. An
      additional program allows one to display the trends again and to create table
      text files containing all the recorded data for further analysis. The system
      proved to work in ICU and anaesthesia patients with various ventilators.

PMID- 8529352
TI  - Interactive database management (IDM).
AB  - Interactive database management (IDM) is a data editing software that provides
      complete data editing at the time of initial data entry when information is
      'fresh at hand'. Under the new interactive system, initial data recording is
      subjected to instant data editing by the interactive computer software logic.
      Data are immediately entered in final form to the database and are available for
      analysis. IDM continuously checks all variables for acceptability, completeness,
      and consistency. IDM does not allow form duplication. Many functions including
      backups have been automated. The interactive system can export the database to
      other systems. The software has been implemented for two Department of Veterans
      Affairs Cooperative Studies (CCSHS #5 and CSP #385) which collect data for 1400
      and 1000 variables, respectively at 28 VA medical centers. IDM is extremely user
      friendly and simple to operate. Researchers with no computer background can be
      trained quickly and easily to use the system. IDM is deployed on notebook
      microcomputers making it portable for use anywhere in the hospital setting.

PMID- 8529353
TI  - An instrument for real-time spectral estimation of heart rate variability
      signals.
AB  - A Digital Signal Processor (DSP)-based instrument is proposed for estimating and
      displaying the Heart Rate Variability (HRV) spectrum in real-time. It consists of
      an intelligent module which is properly interfaced to an IBM PC and whose
      operations are independent from the computer's other tasks. In this way, the
      simultaneous recording of the ECG sequence, needed for the more complete off-line
      analysis, can be performed by the same host. The employed hybrid spectral
      estimator (in which a classical FFT analysis follows the autoregressive
      extrapolation of data) appears to be the most apt for the present fixed point
      arithmetics implementation. The reliability of the instrument and its accuracy
      are checked both with suitable test signals and by comparison with the results
      obtained through off-line analysis of the same ECG tracks. The instrument is
      presently used for cardiovascular investigations, in particular for quickly
      picking patients with cardiac autonomic neuropathy (CAN) out of a population of
      diabetic subjects.

PMID- 8529354
TI  - WENDEC: a deconvolution program for processing hormone time-series.
AB  - The estimation of the glandular secretory rate from time-series of hormone
      concentration in plasma can be formulated as a deconvolution problem. In
      particular, the paper addresses the analysis of frequently sampled data collected
      in order to study spontaneous pulsatile secretion. Standard deconvolution methods
      do not allow for the non-negativity constraint and the presence of high-frequency
      components in the secretory rate. In order to overcome the intrinsic ill
      conditioning of the problem, the maximum entropy method is used to obtain a
      probabilistic representation of the prior knowledge concerning the unknown
      secretory signal, thus leading to a White Exponential Noise (WEN) model. The
      deconvolution problem is then posed within a Bayesian framework and solved by
      means of Maximum-A-Posteriori estimation. The program that implements the
      algorithm handles non-negativity constraints, provides confidence intervals, and
      is computationally and memory efficient.

PMID- 8529355
TI  - A computer-based book on medical helminthology.
AB  - A computer assisted book on medical helminthology has been prepared using ZOOM, a
      teaching computer program, which uses hypermedia technology to link pictures and
      text. Information on various helminths, including their morphology, life cycle,
      clinical manifestations, diagnosis, treatment and epidemiology can be easily
      accessed using three types of link in a non-linear approach. The book consists of
      five chapters, each contains the latest information on various aspects of
      helminth parasites. New information can easily be added to each chapter by the
      user. References can be assessed and updated for each parasite. The book is
      designed for students of medical schools, health administrators and physicians in
      developing countries.

PMID- 8529356
TI  - Software tools for using a personal computer as a timer device to assess human
      kinematic performance: a case study.
AB  - Frequently, the assessment of the physical condition of a sportsman depends on
      the evaluation of different tests, based on biomechanical performance. The data
      acquisition in these tests is usually hand made, because its automatization is
      difficult. But when movements are constrained by means of their specific nature,
      simple tools can be used to achieve that data acquisition. In this paper, a
      simple and inexpensive system is described to make use of the timing capabilities
      of a personal computer (PC) to use it as a timer, with applications in
      biomechanics and sport training. The data acquisition method is based on a PC
      that, using a specific programming dealing with event timing, gets signals
      through the printer port, from a receptor device that detects cuts in an infrared
      cell beam. Low level procedures are provided that can be used in higher level
      algorithmic designs, problem dependent, to build specific systems. The case of
      the evaluation of the Wingate Anaerobic Test is discussed.

PMID- 8529357
TI  - An event recorder for infant feeding research.
AB  - An Event Recorder program was developed for the HP 48 calculator to record the
      durational events associated with breastfeeding behavior. The Event Recorder menu
      structure is flexible and allows for the recording of response variables such as
      menstrual history and fertility symptoms. A Windows program was written in Visual
      C++ to give a graphical representation of the time-series data and to extract
      useful measures of breastfeeding activity from the raw data for each 24-h day
      postpartum. These time varying covariates include the mean and median bout
      length, median interbout interval, breastfeeding frequency and total 24-h
      suckling duration. The HP 48 calculator has proven to be a robust instrument for
      the self-recording of breastfeeding data collected as part of a prospective study
      on the factors that maintain postpartum amenorrhea. We have found also that the
      behavioral data collected are easily transferred electronically each month when
      our field workers make home visits.

PMID- 8529358
TI  - Pathobiology of the endothelium in multiple organ dysfunction syndrome.

PMID- 8529359
TI  - Mediators in continuous extracorporeal treatment of multiple organ dysfunction
      syndrome.

PMID- 8529360
TI  - Continuous hemofiltration in phase of recovery from septic shock.

PMID- 8529361
TI  - Effects of continuous venovenous hemofiltration on pulmonary function and
      hemodynamics in postoperative septic multiorgan failure.

PMID- 8529362
TI  - Continuous monitoring of cardiac output during hemodialysis.

PMID- 8529363
TI  - Continuous extracorporeal treatment in patients with normal renal function?

PMID- 8529364
TI  - Nonrenal indications for continuous hemofiltration therapy in patients with
      normal renal function?

PMID- 8529365
TI  - Low-dose heparinization for anticoagulation in intensive care patients on
      continuous hemofiltration.

PMID- 8529366
TI  - Use of prostacyclin in patients with continuous hemofiltration after open heart
      surgery.

PMID- 8529367
TI  - Influencing hemostasis during continuous venovenous hemofiltration after acute
      renal failure: comparison with intermittent hemodialysis.

PMID- 8529368
TI  - Influence of coagulation parameters on filter running time during continuous
      venovenous hemofiltration.

PMID- 8529369
TI  - The mechanism of postoperative blood loss reduction by ultrafiltration in cardiac
      surgery is unlikely to be only mediated by hemoconcentration of coagulation
      factors.

PMID- 8529370
TI  - Antithrombin III deficiency during continuous venovenous hemodialysis.

PMID- 8529371
TI  - Thromboelastography and monitoring of coagulation in patients undergoing
      continuous venovenous hemofiltration.

PMID- 8529372
TI  - Prognostic importance of vital organ dysfunction in sepsis.

PMID- 8529373
TI  - Prognosis in pediatric patients with multiple organ system failure and continuous
      extracorporeal renal support.

PMID- 8529374
TI  - Early experience with a new hemodiafilter for small infants.

PMID- 8529375
TI  - Continuous venovenous hemofiltration in a seven-year-old child suffering from
      severe sepsis and multiple organ failure.

PMID- 8529376
TI  - Removal of complement fragments by ultrafiltration during pediatric
      cardiopulmonary bypass.

PMID- 8529377
TI  - Intensive care management of patients with acute hepatic and renal failure.

PMID- 8529378
TI  - Continuous renal replacement therapies: the need for a standard nomenclature.

PMID- 8529379
TI  - Comparison between continuous venovenous and intermittent hemodialysis in acute
      renal failure.

PMID- 8529380
TI  - Continuous venovenous hemofiltration in acute renal failure: is a bicarbonate- or
      lactate-buffered substitution better?

PMID- 8529381
TI  - Removal of methotrexate by continuous venovenous hemodiafiltration.

PMID- 8529382
TI  - Hemofiltration in a nephrotic syndrome of unknown origin.

PMID- 8529383
TI  - Influence of venovenous hemofiltration on posttraumatic inflammation and
      hemodynamics.

PMID- 8529384
TI  - Cytokine kinetics (TNF-alpha, IL-1 beta, IL-6) during continuous hemofiltration:
      a laboratory and clinical study.

PMID- 8529385
TI  - Hemofiltration in human sepsis: evidence for elimination of immunomodulatory
      substances.

PMID- 8529386
TI  - Complement fragments and cytokines: production and removal as consequences of
      hemofiltration.

PMID- 8529387
TI  - Ultrafiltration allows to reduce cytokine plasma concentrations during pediatric
      cardiopulmonary bypass.

PMID- 8529388
TI  - Effect of continuous hemodiafiltration on IL-6, TNF-alpha, C3a, and TCC in
      patients with SIRS/septic shock using two different membranes.

PMID- 8529389
TI  - The influence of continuous hemofiltration on cytokine elimination and the
      cardiovascular stability in the early phase of sepsis.

PMID- 8529390
TI  - Topographic concepts in computerized electrocardiology.
AB  - Modern approaches to automatized electrocardiological diagnostics are mostly
      based on topographic conception. Thus, initially measured data and the results of
      data processing are represented by parameters distributed over a surface instead
      of by the separate time-dependent curves of usual electrocardiograms. Examples of
      the topographic approach are found in measuring and analyzing body-surface
      (including precordial) potential distributions, epicardial and endocardial
      potential distributions, heart surface distributions of the intensity of an
      equivalent bioelectric generator, significant electrophysiological
      characteristics of the bioelectrical processes in myocardium, etc. The main
      advantage of using topographic methods is the ability to comprehensively collect
      and efficiently analyze all diagnostic information about the electrophysiological
      state of the heart. Rather useful additional information may be acquired by means
      of biomagnetic field measurements on the basis of similar topographic techniques.
      A critical review of recent biophysical, measuring, and computational problems,
      as well as theoretical and experimental results in the field of topographic
      electrocardiology is presented.

PMID- 8529391
TI  - Interpreting culture and psychopathology: primitivist themes in cross-cultural
      debate.
AB  - Interpreting the cross-cultural incidence of psychopathology is a focus of
      continuing debate. This paper explores the lineaments of that debate and its
      underlying premises concerning difference and distance. Primitivism--a body of
      ideas, images and vocabularies about cultural others--is characteristically
      employed to represent non-Western peoples. But it is more fundamentally concerned
      with the way the West understands itself in contradistinction to these others. It
      is shown to be a major source of the images used to think about mental illness,
      and of the intellectual traditions which have constituted cross-cultural
      psychiatry as a comparative discipline. Psychiatric primitivism employs two
      opposing perspectives, which we have labelled 'Barbaric' and 'Arcadian'
      respectively. They are the source of contradictory assertions concerning the
      relationship between culture and mental illness. They provide the framework which
      structures contemporary research into the cross-cultural incidence and course of
      schizophrenia, shaping its methodology, its rhetoric, the strategies by which
      data are interpreted, and the conclusions which it draws. We demonstrate a
      convergence of themes whereby images of society, person and mental illness come
      to signify each other. This is epitomized in three of cross-cultural psychiatry's
      principal subject areas: amok, shamanism, and the therapeutic quality of
      'traditional' society.

PMID- 8529392
TI  - The expression of emotional distress in old English prose and verse.
AB  - The Old English elegies and Alfred's translation of De Consolatione Philosophiae
      were examined for the presence of abstract nouns denoting adverse mood states.
      Large numbers of these nouns were discovered and grouped into five categories.
      This counters the arguments of those who believe the Anglo-Saxons expressed
      negative emotions chiefly in somatic terms.

PMID- 8529393
TI  - The effectiveness of words: religion and healing among the Lubavitch of Stamford
      Hill.
AB  - Testimonials of miraculous healing offered by Lubavitch Hasidim evoke images of
      exile and restitution which derive from Kabbalistic texts. Mediated practically
      through the person of the Rebbe, these testimonials articulate both immediate
      affliction and ultimate meaning, physical embodiment as well as symbolic
      representation, each constituting the other. Both Kabbalah and medical
      anthropology attempt to transcend not dissimilar epistemological dualisms: those
      characteristic of monotheism and contemporary science. Yet the 'lower root' of
      Kabbalah affirms a material reality known through immediate sensory experience
      which recalls the rationale of biomedicine.

PMID- 8529394
TI  - Naming and grouping illnesses in Feira (Brazil).
AB  - This paper examines the naming and grouping of illnesses in the popular medicine
      of Feira de Santana, a city in Northeastern Brazil, in a context of medical
      pluralism. It discusses the principles used to name illnesses in Feira and the
      semantic shifts evident in popular nomenclature; examines the grouping of
      illnesses in Feira; and shows the flexibility of these situationally negotiated
      categorizations. It also analyzes the place of symptoms in local nosological
      knowledge and examines three folk illnesses as an illustration of the discussion
      of illness classification.

PMID- 8529395
TI  - Anthropology's Hoodoo Museum.

PMID- 8529396
TI  - In vitro studies of human choroidal endothelial cells.
AB  - Vascular endothelial cells play an important role in progression or healing of
      various retinal or choroidal diseases and they have a broad organ specificity. We
      have grown and studied human choroidal endothelial cells (CECs) cultured in a
      collagen gel, where they form tube-like structures. CECs were differentially
      isolated from choroidal tissues and cultured to near homogeneity. The cells were
      embedded in a type I collagen gel in 24-well culture dishes and incubated with
      M199 medium containing 10% fetal calf serum. Gels were observed using phase
      contrast microscopy and were evaluated histologically by light and electron
      microscopy. The CECs were strongly positive for factor VIII-related antigen and
      actively ingested diI-acetylated LDL, indicating their endothelial nature.
      Ultrastructural analysis of the tube-like structures revealed a central lumen
      surrounded by cells joined apically by junctions and showing prominent
      pinocytotic activity, fenestrations and basement membrane formation; these
      features are typical of CECs in vivo. This preparation should be a useful tool to
      study the development of physiology and pathology of choroidal endothelium.

PMID- 8529397
TI  - Drug-dependent Ca2+ mobilization in organ-cultured rabbit ciliary processes.
AB  - This study was conducted to determine whether drug-dependent changes in cytosolic
      Ca2+ concentration take place in the ciliary nonpigment epithelial cells of
      rabbits under more physiological conditions. Iris-ciliary body from pigmented
      rabbits in organ-culture was loaded with a Ca(2+)-sensitive fluorescent dye, fura
      2, and a video-imaging system with an image analyzer was employed. Using this
      method fluorescence from nonpigmented epithelial cells can be analyzed without
      interference from fluorescence from pigmented ciliary epithelial cells. Among the
      drugs studied, norepinephrine and carbachol induced Ca2+ transients in the
      nonpigmented epithelial cells of organ-cultured ciliary processes. Epinephrine,
      isoproterenol, dopamine, neuropeptide Y, and substance P at the concentration of
      10(-6) to 10(-3) M failed to elicit a response. The cytosolic free Ca2+
      concentration of the cells in the resting state, as determined by an in vitro
      calibration curve, was 166 nM. The peak free cytosolic Ca2+ concentration induced
      by norepinephrine was about 263 nM, and that induced by carbachol was more than
      1,000 nM. The carbachol-induced response was larger in magnitude and longer in
      duration than that induced by norepinephrine. Not uncommonly, the carbachol
      induced response lasted more than 15 min. The response was diminished in both
      peak height and duration by chelation of extracellular Ca2+. Atropine abolished
      the response showing the response being mediated by a muscarinic receptor.

PMID- 8529398
TI  - Development of a chitin assay for the quantification of fungus.
AB  - Chitin, a unique structural polysaccharide found in fungi and arthropods, is not
      produced by vertebrates. Thus, the potential applications of a specific and
      sensitive assay for chitin are numerous, including the evaluation of the extent
      of fungal keratitis. Chitin is a homopolymer of beta (1, 4) linked D-N
      acetylglucosamine. We have developed a simple and reproducible assay for chitin
      and applied it to Candida albicans cultures. The assay involves homogenization of
      the culture and treatment with 21.1 M KOH to remove soluble materials, including
      proteins. This base treatment also deacetylates the chitin to the glucosamine
      polymer, chitosan. Chitosan is hydrolyzed by 0.5 M H2SO4 to glucosamine monomers
      which are then deaminated by the addition of NaNO2 to the acid solution. The
      resulting 2,5-anhydromannose is reduced by NaB[3H]4 to 1-[3H] 2,5
      anhydromannitol. This radiolabelled sugar is isolated by paper chromatography and
      quantified via liquid scintillation. The sensitivity of this assay is assessed by
      comparison of colony forming units (CFU's) with a glucosamine standard. A typical
      run of the assay detects 53.1 CFU/c.p.m., and 356,000 c.p.m. per nanomole of N
      acetylglucosamine. The specificity of the assay is very high because of the
      unique nature of chitin. This method of chitin determination may be a useful
      alternative method for future investigations involving the study of fungal
      infections in mammalian tissues.

PMID- 8529399
TI  - Prevention of oxidative damage to rat lens by pyruvate in vitro: possible
      attenuation in vivo.
AB  - Studies have been conducted to assess the possible preventive effect of pyruvate
      against lens protein oxidation and consequent denaturation and insolubilization.
      Rat lens organ culture system was used for these studies. The content of water
      insoluble proteins (urea soluble) increased if the lenses were cultured in medium
      containing hydrogen peroxide. Incorporation of pyruvate in the medium prevented
      such insolubilization. The insolubilization was associated primarily with loss of
      gamma crystallin fraction of the soluble proteins. PAGE analysis demonstrated
      that insolubilization is related to -S-S- bond formation which was preventable by
      pyruvate. Since pyruvate is a normal tissue metabolite the findings are
      considered pathophysiologically significant against cataract formation. This was
      apparent by the prevention of selenite cataract in vivo by intraperitoneal
      administration of pyruvate.

PMID- 8529400
TI  - The influence of thapsigargin on Na,K-ATPase activity in cultured nonpigmented
      ciliary epithelial cells.
AB  - Experiments were conducted to test the influence of thapsigargin on the NaK
      ATPase activity of cultured cells (ODM2) derived from human nonpigmented ciliary
      epithelium. The rate of ouabain-sensitive ATP hydrolysis (Na,K-ATPase activity)
      was diminished in cells that had been pretreated with thapsigargin then
      permeabilized. Following 20 min exposure of intact cells to thapsigargin, the
      cells were permeabilized with digitonin and the rate of ouabain-sensitive ATP
      hydrolysis (Na,K-ATPase activity) was measured immediately in a calcium-free
      buffer. In permeabilized cells that had been pretreated with 1 microM
      thapsigargin for 20 min, the rate of ouabain-sensitive ATP hydrolysis (Na,K
      ATPase activity) was reduced by 38%. Pretreatment with lesser concentrations of
      thapsigargin caused smaller changes of Na,K-ATPase activity. The decrease of Na,K
      ATPase activity was the same whether or not calmodulin antagonists W7 or
      trifluoperazine were present during the thapsigargin pretreatment period. This
      inhibitory effect upon the Na,K-ATPase may serve to limit the extent of sodium
      pump activation that takes place in intact cells when thapsigargin causes sodium
      pump stimulation by a mechanism that appears to involve changes in cytoplasmic
      ion levels when potassium channels open.

PMID- 8529401
TI  - A subconjunctival degradable implant for cyclosporine delivery in corneal
      transplant therapy.
AB  - The effect of local cyclosporine therapy upon corneal transplant survival was
      investigated. A high risk rabbit model with vascularized corneas was used to
      assess the efficacy of subconjunctivally implanted degradable devices for
      cyclosporine therapy. Animals were divided into four groups, receiving either no
      therapy, a placebo PLGA device, or drug containing devices implanted either at
      the time of transplantation or two weeks previous. The mean survival times of
      animals in the control and placebo groups were statistically equivalent (21 +/- 4
      days vs 18 +/- 4 days). Devices containing CsA improved the survival time of
      grafts. Predosing the animals with CsA improved the survival time to 28 +/- 7
      days, and CsA devices implanted at the time of transplantation increased the
      survival time to 35 +/- 7 days. The improvement in survival times was consistent
      with the in vitro drug release profiles. No systemic CsA was detected, suggesting
      that the effect may have been local. Histological assessment indicated that
      devices were well tolerated.

PMID- 8529402
TI  - Insulin-like growth factor-I promotes cell proliferation in the absence of
      modulation of collagen phenotypes and utilizes IRS-1, not PLC-gamma 1, in corneal
      endothelial cells.
AB  - Corneal endothelial cells are differentiated cells and are thus incapable of
      physiologic regeneration. In a search for a growth factor that would promote
      optimal proliferation of corneal endothelial cells in the absence of other
      modulating activities, the effect of insulin-like growth factor-I (IGF-I) on
      rabbit corneal endothelial cells was studied. In addition, cellular effector
      molecules responsible for the signal pathway for IGF-I were studied. IGF-I at 50
      ng/ml stimulated corneal endothelial cell proliferation after at least 8 h of
      treatment. IGF-I did not change cell shape of corneal endothelial cells: the
      cells treated with IGF-I at 50 ng/ml maintained polygonal morphology regardless
      of the duration of exposure. IGF-I did not alter collagen phenotypes either
      qualitatively or quantitatively: the treated cells continued to synthesize types
      IV and VIII collagen, as did the control cells. The steady-state levels of alpha
      2(I) collagen RNA and alpha 2(IV) RNA were not altered by IGF-I treatment.
      Immunohistochemical analysis showed that IGF-I is present in corneal endothelium
      in vivo, while the underlying Descemet's membrane demonstrated no staining.
      Corneal endothelial cells also produce IGF binding protein-2 (IGFBP-2), which
      appears to bind IGF-I that has been introduced exogenously in the medium. Further
      investigation as to how the signals of IGF-I were transmitted for the biological
      activities demonstrated that the expression of insulin receptor substrate-1 (IRS
      1) is up-regulated by IGF-I treatment, while PLC-gamma 1 expression is not
      altered by this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529403
TI  - An improved method of isolating fetal human retinal pigment epithelium.
AB  - The purpose of this study was to develop an improved method of isolating fetal
      human retinal pigment epithelium (RPE) for tissue culture or transplantation.
      Fetal human eyes ranging from 8 to 20 wks of gestation were collected and stored
      in Optisol solution. Under a dissecting microscope, an incision was made behind
      the ora serrata and extended circumferentially to remove the anterior segment.
      The vitreous was withdrawn, and the neural retina was carefully detached from the
      RPE. The sclera then was teased away from the choroid-RPE. The choroid-RPE was
      treated with 2% dispase in DMEM + 20 mM HEPES at 37 degrees C for 25 min. While
      still in dispase, the RPE was separated from the choroid using a pair of fine
      tipped jeweler's forceps under dark-field. An intact sheet of RPE could be
      separated from the choroid after treatment with dispase. No choroidal
      contamination was present as determined by light microscopy or cell culture. In
      vitro, the isolated RPE cells demonstrated classic cobblestone phenotype and
      expressed cytokeratin. This technique provides an easy and reliable method for
      isolating pure sheets of fetal human RPE. It also allows utilization of the
      neural retina of the same eye for other purposes, as the neural retina is not
      exposed to the enzymatic digestion. These features make this method especially
      useful for RPE and retinal transplantation; such an application is already
      underway.

PMID- 8529404
TI  - Effects of adenosine on chick retinal pigment epithelium: membrane potentials and
      light-evoked responses.
AB  - We examined the effects of adenosine, a putative mediator of neuroprotection
      during cerebral ischemia, on the electrophysiological characteristics of retina
      retinal pigment epithelium-choroid preparations obtained from 1-7 day-old chick
      and maintained in vitro. Our experiments produced the following results. First,
      superfusion of the retinal surface with adenosine (0.1 mM) increased the trans
      tissue potential. The trans-epithelial (but not the trans-retinal) potential was
      also increased to the same magnitude with a time-course similar to that of the
      trans-tissue potential. Second, adenosine produced a depolarization of the
      epithelial basal plasma membrane with a concomitant decrease in its basal
      membrane resistance. Third, the trans-epithelial (but not the trans-retinal) c
      wave in response to a light stimulus was augmented by adenosine. Adenosine
      reduced the hyperpolarization of the epithelial basal membrane, but had no effect
      on the extracellular concentration of K+ in the subretinal region. Fourth, the
      light-peak that was elicited with a 300 s light stimulus was also depressed by
      adenosine. Fifth, when 4,4'-diisothiocy anostilbene-2,2'-disulfonate (DIDS), a
      relatively selective inhibitor of Cl- channels, was perfused at 50 microM on the
      choroidal surface, adenosine-induced increases in the trans-tissue potential and
      the c-wave were both abolished. These results suggest that adenosine increased
      the Cl- conductance of the basal plasma membrane of the retinal pigment
      epithelium and thereby augmented the standing potential as well as the light
      elicited membrane potentials of the retinal pigment epithelium, which seems to be
      involved in the pathophysiology of retinal ischemia.

PMID- 8529405
TI  - Vitamin E in macular and peripheral tissues of the human eye.
AB  - This study was undertaken to investigate the distribution of vitamin E in the
      macular and peripheral regions of the human retina, retinal pigment epithelium
      (RPE) and choroid as a function of age. High-performance liquid chromatography
      (HPLC) was used to measure alpha- and gamma-tocopherol levels quantitatively
      using tocol as an internal standard. In 57 out of 70 donor eyes (ages 9-104) the
      macular region was isolated and the tocopherols analyzed. The conventional brush
      method and a new vortex method were used to isolate the retinal pigment
      epithelium cells. Similar trends for the vitamin E levels (increase to the 5th
      decade, decrease after 7th decade) were found for the macular and peripheral
      retina and for the macular RPE. In the peripheral RPE a slight continuous
      increase with age was found. The vitamin E levels are higher in the RPE than in
      the retina, for both macular and peripheral regions. The amounts of vitamin E/mg
      protein are lower in the macular retina than in the peripheral retina, whereas in
      the RPE there is no difference in vitamin E content between macular and
      peripheral regions. A simple method based on a gentle vortex step was found to
      offer several advantages over the more generally used isolation of RPE cells
      based on brushing, and there was no difference in recovery of vitamin E in RPE
      cells when they were isolated by either isolation technique. It was also found
      that denominators, used to express the values of vitamin E in tissues should, be
      used with care since age dependent trends in parameters/denominators could be
      caused by trends in the denominators only.

PMID- 8529406
TI  - Immunohistochemical studies on melanin associated antigen (MAA) induced
      experimental autoimmune anterior uveitis (EAAU).
AB  - Experimental autoimmune anterior uveitis (EAAU), a model of uveitis induced by
      sensitization to melanin associated antigen (MAA) derived from the iris and
      ciliary body, closely resembles human acute anterior uveitis. The
      immunopathogenesis of EAAU was studied by immunohistochemical detection of immune
      cells and the expression of Ia, ICAM-1 and LFA-1 antigens. Male Lewis rats were
      immunized with bovine MAA, mixed with CFA and pertussis toxin in the hind foot
      pad. Animals were examined daily by slit-lamp biomicroscopy and serially
      sacrificed up to 30 days. Immunohistology of the enucleated eyes was performed
      with monoclonal antibodies W3/25 (CD4), OX-8 (CD8), ED2 (macrophage), OX-33 (B
      cell), OX-6 (Ia), IA29 (ICAM-1) and WT.1 (LFA-1). During each stage of EAAU, CD4+
      T cells predominated over both CD8+ T cells and macrophages in the uvea. Very few
      B cells were detected during each stage of EAAU. EAAU could not be induced by the
      adoptive transfer of sera obtained from immunized animals. Low levels of
      constitutive ICAM-1 and Ia were observed. An increase in ICAM-1 expression was
      first noted on the epithelial cells of the uveal tract and RPE on day 9 post
      immunization and preceded LFA-1 and Ia upregulation by approximately 2 days. The
      immunopathogenesis of EAAU appears to be linked to the presence of the CD4+ T
      cells.

PMID- 8529407
TI  - Long-term non-invasive measurement of intraocular pressure in the rat eye.
AB  - To study the optic neuropathy associated with glaucoma, a system for accurate,
      reliable, and non-invasive monitoring of intraocular pressure (IOP) is required.
      Of particular interest is the effect of sampling frequency on IOP. To address
      this issue, ten adult male brown Norway rats (group 1) were acclimatized to a 12
      h/12-h light/dark cycle. On 20 days over a 30-day period, rats were anesthetized
      with short-acting isoflurane (Forane) inhalant anesthesia and IOP for each eye
      was determined by averaging 15 valid individual readings obtained with a TonoPen
      2 tonometer. The last 12 measurement sessions were performed on a daily basis. To
      determine the minimum tolerable interval between IOP measurement sessions, a
      second group of 10 animals (group 2) was acclimatized in the same manner as group
      1, and IOP was measured every 4 days over a period of 80 days. Next, IOP was
      measured every 4 days over a period of 28 days, and finally, every 2 days over a
      period of 19 days. For all group 1 measurements, there was no statistically
      significant difference between the right and left eye IOP, 14.75 +/- 1.08 (SEM)
      and 14.90 +/- 1.09 mm Hg, respectively. However, daily measurements produced a
      steady decrease in IOP and gradual weight loss. For group 2, overall mean right
      and left eye IOPs were 15.24 +/- 1.28 (SEM) and 15.12 +/- 1.26, respectively and
      were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529408
TI  - Anti-leukocyte function-1 antibody treatment prevents the rejection of
      intraocular regressor tumors and their metastases.
AB  - The role of the cell adhesion molecules, LFA-1 and ICAM-1, in intraocular tumor
      rejection was examined using four different syngeneic intraocular regressor
      tumors and four different inbred mouse strains. All four tumors undergo T cell
      dependent immune rejection in the syngeneic host. Two of the tumors, D5.1G4
      melanoma and P91 mastocytoma, undergo rejection by a cytotoxic T lymphocyte-like
      immune process. The other two tumors, UV5C25 fibrosarcoma and 124E2 melanoma, are
      rejected by a process that appears to be mediated by delayed-type
      hypersensitivity. Systemic administration of anti-LFA-1 prevented the rejection
      of all four categories of tumors. By contrast, similar in vivo treatment with
      anti-ICAM-1 antibody did not inhibit tumor rejection. The effect of anti-LFA-1
      and anti-ICAM-1 antibody treatment on the rejection of metastases arising from
      intraocular P91 tumors was also examined and found to be highly dependent upon
      normal LFA-1 function since antibody treatment with anti-LFA-1 prevented the
      rejection of metastases. Treatment with anti-ICAM-1 antibody alone had no
      appreciable effect on the rejection of metastases. The results from this study
      indicate that the expression and function of LFA-1 is crucial for the generation
      of immune responses to tumor antigens originating within the eye and the
      expression of tumor immunity within the eye and at distant sites.

PMID- 8529409
TI  - Localization and possible gene expression of proteoglycan decorin in the
      trabecular meshwork.
AB  - It is known that trabecular meshwork cells produce proteoglycans and that local
      production may be associated with aqueous outflow resistance. In an attempt to
      identify intraocular production of proteoglycan decorin in the anterior chamber
      angle of mammalian eyes, we conducted a Northern blot analysis and
      immunohistochemical studies. Northern blot analysis suggested gene expression of
      proteoglycan decorin in trabecular meshwork cells. Also, immunohistochemical
      studies using anti-decorin antibody demonstrated decorin-like immunoreactivity in
      the trabecular meshwork and around the Schlemm's canal. Our data demonstrate the
      presence of proteoglycan decorin in the outflow pathway, suggesting that decorin
      is a component of extracellular matrices in these regions and may be associated
      with outflow resistance.

PMID- 8529410
TI  - Calpain activity in the retinas of normal and RCS rats.
AB  - Calpains are calcium-activated proteinases which have been implicated in tissue
      differentiation and degeneration. The aims of the present study were: (1) to
      determine the relationship between postnatal age and calpain activity in the rat
      retina; (2) to test if calpain activity was aberrant in the RCS retina at
      different postnatal ages. Calpain activity was measured by a standard in vitro
      assay in fractions of retinas of rats, ranging in postnatal age of 2 to 42 days.
      Most retinal calpain activity was in the cytosolic fraction. Specific calpain
      activity declined with age. In the Long Evans rat, it was 8-fold higher on
      postnatal day 2 than on postnatal day 42. Comparison between RCS rats and their
      congenic controls showed that calpain activity was lower in the retinas of
      neonatal RCS rats. Specific calpain activity in RCS rat retinas was 46% lower on
      postnatal day 2 and 22% lower on postnatal day 3. It is concluded that during
      postnatal development of the retina, marked changes occurred in calpain activity.
      In addition, calpain activity is abnormal in the retina of the neonatal RCS rat-
      well before the onset of any morphological deterioration and preceding any other
      previously detected abnormality. Aberrant calpain activity appears to be a
      manifestation of very early events in processes that lead to retinal degeneration
      in the RCS rat.

PMID- 8529411
TI  - The effect of litter size on normal retinal vascular development in the neonatal
      rat.
AB  - Many animal models of retinal disease use the neonatal rat. Raising rat pups in
      large litters has been shown to result in postnatal growth retardation. We
      investigated the effect of litter size on the normal postnatal vascularization of
      the neonatal rat retina. Sixty-six newborn rat pups were divided among 5 nursing
      mothers into 3 small litters (n = 10) and 2 large litters (n = 18). On day 6 of
      life the rats were sacrificed and total retinal and vascularized retinal areas
      analyzed. The total retinal area was reduced in the rats raised in larger litters
      (28.6 mm2 vs. 25.9 mm2 p < 0.001) but there was a more pronounced reduction in
      vascularized retinal area (67% vascularized vs. 54% vascularized, p < 0.001).
      Postnatal vascularization of the normal rat retina may be influenced by litter
      size.

PMID- 8529412
TI  - Reversal of abnormal retinal hemodynamics in diabetic rats by acarbose, an alpha
      glucosidase inhibitor.
AB  - Acarbose is an inhibitor of intestinal alpha-glucosidase and has been reported to
      decrease blood glucose concentrations and glycosuria in diabetic patients and
      animals. In this study we investigated whether this drug could prevent the
      abnormalities detected in retinal circulation of diabetic rats. Longitudinal
      paired studies were performed and the changes in retinal circulation were
      analyzed using video based fluorescein angiography (VFA) methodology in the same
      animal. Baseline VFA recordings were obtained from 41 rats. These rats were
      separated into 4 different groups: In group A (n = 12), diabetes was induced by
      streptozotocin (STZ) injection and the rats were fed with acarbose (40 mg/100 g
      powdered chow) mixed into regular rat chow; In group B (n = 10), diabetes was
      induced by STZ injection and the rats were fed with normal chow; In group C (n =
      9), the non-diabetic rats were fed with acarbose; In group D (n = 10), the non
      diabetic rats were fed with normal chow. At the end of 2 weeks, all rats again
      underwent VFA recordings. Blood glucose levels and body weights of rats were
      monitored during the experiment. The mean blood glucose concentration of Group B
      was raised from 98.5 +/- 8.7 to 342 +/- 30 mg/dl after STZ injection while in
      Group A, this change in glucose level was partially ameliorated by acarbose (from
      102 +/- 15 to 247 +/- 48 mg/dl). In Group C and D, the blood glucose levels were
      not significantly changed during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529413
TI  - A comparison of ubiquitin-dependent proteolysis of rod outer segment proteins in
      reticulocyte lysate and a retinal pigment epithelial cell line.
AB  - We compared ATP- and ubiquitin-dependent proteolysis in supernatants of rabbit
      reticulocyte lysate and a human retinal pigment epithelial (RPE) cell line. At pH
      7.8, both preparations catalyzed the conjugation of [125I]ubiquitin to endogenous
      proteins, generating an equivalent amount of high mass (> 150 kDa)
      [125I]ubiquitin-protein adducts. Both preparations degraded exogenous histone 2A,
      oxRNase and beta-lactoglobulin in an ATP-dependent manner. Addition of ubiquitin
      (12 or 120 microM) to reticulocyte lysate stimulated (1.4-fold) ATP-dependent
      degradation only of histone 2A. Addition of 12 microM ubiquitin to RPE
      supernatant resulted in > or = 3-fold enhancement in degradation of all three
      substrates. Next, we compared the ability of the two proteolysis systems to
      degrade bovine rod outer segment (ROS) nonintegral membrane proteins. [125I]ROS
      protein degradation by reticulocyte lysate was almost exclusively ATP-dependent
      and was completely inhibited by hemin and vanadate, inhibitors of ATP- and
      ubiquitin-dependent proteolysis. RPE supernatant also degraded ROS proteins by an
      ATP-dependent mechanism, and, unlike results obtained in reticulocyte assays,
      this degradation increased (2-fold) upon ubiquitin supplementation. Both
      proteolysis systems degraded ROS proteins of molecular mass approximately 10, 30,
      37, 40 and 60 kDa, with coincident formation of high mass species. Reticulocyte
      lysate also degraded 100 and 150 kDa ROS proteins, whereas RPE supernatant did
      not. The 10, 37 and 40 kDa species were identified by western blot as the gamma-,
      beta- and alpha- subunits of rod transducin (Gt), respectively. RPE supernatant
      generated (some) ROS proteolysis products that remained acid-precipitable. As
      compared with patterns of proteolysis in reticulocytes, RPE supernatant (1)
      degraded 100% more Gt beta gamma, (2) generated > 10-fold the amount of high mass
      (putative ubiquitin-ROS protein) conjugates and (3) preferentially degraded Gt
      beta gamma relative to G t alpha. The ubiquitin-dependent enhancement of ATP
      dependent degradation of all proteins tested in RPE supernatant makes the RPE
      system a valuable experimental tool for the explicit demonstration of ubiquitin
      dependent proteolysis.

PMID- 8529414
TI  - Biodegradation and tissue reaction to intravitreous biodegradable poly(D,L-lactic
      co-glycolic)acid microspheres.
AB  - We studied the biodegradation of and the tissue reaction to microspheres of 50:50
      poly(D,L-lactic-co-glycolic)acid (PLGA) (viscosity-average MW: 3000 d), injected
      intravitreous in rabbits. These microspheres are under investigation as
      injectable devices for intravitreous sustained drug delivery. The rate of
      intravitreous degradation of PLGA microspheres has not been well documented in
      the literature. Twenty two pigmented rabbits underwent gas vitrectomy in one eye:
      19 eyes received 2.5 mg of PLGA microspheres in 1 ml of balanced salt solution
      (BSS) and 3 control eyes received 1 ml of BSS only. Slit lamp exam and indirect
      ophthalmoscopy were performed periodically from day 1 to 6 months after surgery.
      The eyes were enucleated and studied by light microscopy and immunohistochemistry
      at various time points. The electroretinogram (ERG) was recorded in a subgroup of
      rabbits before injection and after 1 and 6 months. The amount of microspheres in
      the vitreous cavity progressively decreased. At 6 months microspheres were found
      in 1/4 rabbits at indirect ophthalmoscopy and in 4/4 rabbits histopathologically.
      A mild localized, non progressive foreign body reaction was observed. The cell
      reaction was composed mostly of vimentin and glial fibrillary acidic protein
      positive cells which probably represent glial cells and fibroblasts. The choroid
      and retina were normal. The ERG showed no abnormalities. No clinical inflammatory
      signs were observed 4 days postoperatively and thereafter.

PMID- 8529415
TI  - Platelet-activating factor preferentially stimulates the phospholipase
      A2/cyclooxygenase cascade in the rabbit cornea.
AB  - Platelet-activating factor (PAF) is formed in the cornea after injury as well as
      by infiltrating inflammatory cells. We have studied the effects of PAF on the
      release and metabolism of arachidonic acid (AA) in the rabbit cornea. Corneal
      lipids were labeled in vivo by injecting [3H]AA and subsequently incubated in
      vitro with 100 nM PAF in the presence or absence of 10 microM BN50727, a PAF
      antagonist. The AA and eicosanoids released by incubated corneas were analyzed by
      high-performance liquid chromatography (HPLC). Tissue lipids were examined by
      mono- and bidimensional thin-layer chromatography (TLC). Within 5 min, PAF
      stimulated AA release to 76% above control levels. BN50727 inhibited the AA
      release elicited by PAF at all time points studied. The decreased content of
      [3H]AA in phosphatidylcholine (PC), phosphatidylethanolamine (PE) and
      phosphatidylinositol (PI) following PAF exposure and the lack of stimulation by
      PAF on the release of [3H] linoleic acid suggest that the cytosolic phospholipase
      A2 was activated. PAF also stimulated depletion of AA from the inositol lipids,
      phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-biphosphate
      (PIP2) and increased content of [3H]AA into diacylglycerol (DAG) and phosphatidic
      acid (PA). This reaction indicates that PAF could also mediate activation of
      other phospholipases in the cornea. In addition, PAF preferentially stimulated
      the cyclooxygenase pathway. The PAF antagonist BN50727 mainly suppressed the PAF
      stimulated release of PGE2. The antagonist did not inhibit lipoxygenase activity
      even after 30 min of PAF stimulation. These results suggest that PAF activate a
      phospholipase A2/cyclooxygenase pathway in the cornea via a PAF-receptor
      mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529416
TI  - Effect of daily topical ethacrynic acid on aqueous humor dynamics in monkeys.
AB  - We determined the effect of 1.5% ethacrynic acid (ECA) in ointment on intraocular
      pressure (IOP) and outflow facility following 5 days of topical treatment in
      ocular normotensive cynomolgus monkeys. Twelve monkeys received a 1 cm strip of
      ointment containing ECA in one eye but without ECA in the other once daily for 5
      days. On Day 1 and Day 5 IOP was measured immediately before and 1 and 3 h after
      treatment. Outflow facility (perfusion) was determined 3.5 h after treatment on
      Day 5. The ECA-vehicle IOP differences averaged -2.8 +/- 0.8 (S.E.M) (p < 0.01), 
      1.7 +/- 0.6 (p < 0.02) and -3.7 +/- 0.7 mm Hg (p < 0.001), equivalent to IOP
      reductions of 21 +/- 6% (p < 0.01), 13 +/- 5% (p < 0.02) and 26 +/- 5% (p <
      0.002) respectively, at 0, 1 and 3 h respectively after treatment on Day 5.
      Facility averaged 40 +/- 15% higher (p < 0.03) in the ECA-treated compared to the
      vehicle-treated eyes 4 h after treatment on Day 5.

PMID- 8529417
TI  - Localization of calcitonin gene-related peptide binding sites in the eye of
      different species.
AB  - The localization of calcitonin gene-related peptide (CGRP) binding sites in the
      eye of monkey, pig, cat and guinea pig was studied by autoradiography. Specific
      binding of CGRP was found in ciliary muscle, ciliary processes and limbal
      conjunctiva in all tested species. Furthermore, specific binding sites of CGRP
      was found in the choroidea of monkey, pig and guinea pig, in the iris of pig, cat
      and guinea pig, in the retina of pig and in the anterior chamber angle of cat.
      The number of specific binding sites varied depending on the tissue and species.
      The present study shows that there are specific binding sites of CGRP in the eye
      of monkey, pig, cat and guinea pig. CGRP binding sites found in vascular system
      of ciliary body, choroidea and iris further demonstrates the role of CGRP as a
      vasoregulatory peptide. Binding sites in the ciliary muscle, in the limbal
      conjunctiva and in the chamber angle area may indicate a role in the regulation
      of ciliary muscle tone, epithelial cell regeneration and aqueous humour outflow.

PMID- 8529419
TI  - Purification and oligomeric state of the major lens fiber cell membrane proteins.
AB  - Purification of the lens fiber cell membrane proteins MP20 and MP26, and the
      partial co-purification of the lens connexin-related proteins MP70 and connexin
      46 has been achieved using anion- and cation-exchange chromatography of lens
      fiber cell membrane proteins solubilized in n-octyl-beta-D-glucopyranoside (octyl
      glucoside). The apparent molecular weights of the solubilized protein-detergent
      complexes were significantly greater than that expected for the monomeric
      proteins. The purified proteins retained their ability to be phosphorylated by
      cAMP-dependent protein kinase, and to bind calmodulin in a calcium and magnesium
      dependent manner. The heterobifunctional covalent chemical crosslinking agent N-5
      azido-2-nitro-benzoyloxysuccinimide (ANB-NOS), and the thiol oxidant cupric
      phenanthroline were used to identify the oligomeric states of these proteins.
      Crosslinking of either the purified proteins or native lens membranes generated a
      ladder of crosslinked MP20 or MP26 homo-oligomers. The largest detectable
      crosslinked homo-oligomer of MP20 was at least a hexamer, while for MP26 the
      largest crosslinked homo-oligomer was at least a tetramer. The possible
      oligomeric states of MP70 and connexin 46 could not be determined with the
      crosslinking reagents used in this study. The procedure described here for the
      purification of detergent-solubilized major lens proteins should provide a
      valuable approach in future studies aimed at clarifying the roles of these
      different lens membrane proteins.

PMID- 8529418
TI  - Ophthalmic arachidonylethanolamide decreases intraocular pressure in normotensive
      rabbits.
AB  - Arachidonylethanolamide (AEA) was the first anandamide to be identified as an
      endogenous ligand for the cannabinoid receptor of porcine brain. Since
      cannabinoids have shown some value in the reduction of ocular hypertension, the
      title compound was evaluated in normotensive rabbits as a possible topically
      applied agent for reducing intraocular pressure. AEA was dissolved in an aqueous
      solution of 2-hydroxy-propyl-beta-cyclodextrin. Single eyedrops (25 microliters)
      containing 3.13, 6.25, 31.25, 62.5 or 125.0 micrograms of AEA were instilled
      unilaterally into eyes of normotensive albino and pigmented rabbits. The
      intraocular pressures (IOPs) of these rabbits were then measured at fixed time
      intervals. The effect of AEA on IOP in treated and untreated (contralateral) eyes
      was similar in both types of rabbits. Administration of 31.25 micrograms of AEA
      caused an immediate IOP reduction in the treated eyes. AEA doses of 62.5
      micrograms caused an initial increase and subsequent decrease of IOP in the
      treated eyes. In the untreated eyes, a marginal ocular hypotensive response of
      limited duration occurred immediately after administration of AEA at doses 31.25
      or 62.5 micrograms. A significant increase (without subsequent decrease below
      baseline) in IOP occurred in treated eyes after a dose of 125.0 micrograms. The
      lowest dose (3.13 micrograms) did not have an effect on IOP. This study
      constitutes the first published demonstration that topical, unilateral
      administration of AEA significantly decreases IOP in normotensive albino and
      pigmented rabbits. Although the mechanism of action by which this compound
      produces its hypotensive effect in the eye is not known, the results suggest that
      AEA may prove useful in the investigation of glaucoma therapy.

PMID- 8529421
TI  - Menadione-dependent alpha glycerophosphate and succinate dehydrogenases in the
      developing canine retina.
AB  - Reducing equivalents for the electron transport chain are generated within the
      mitochondria by the Krebs cycle and in cytoplasm by processes like lipid
      metabolism. Two mitochondrial enzymes, succinate dehydrogenase (SDH), a prominent
      enzyme in the Krebs cycle, and alpha-glycerophosphate dehydrogenase (alpha-GPDH),
      half of the glycerophosphate shuttle system for bringing reducing equivalents
      from cytoplasm to mitochondria, were examined enzyme histochemically to assess
      the contribution of each to metabolism of the developing canine retina. SDH
      activity, a common marker for oxidative metabolism, was insignificant at birth.
      By 4 days of age, activity was observed only in developing photoreceptor inner
      segments. By 21 days of age SDH activity was present throughout the retina,
      especially in photoreceptor inner segments and plexiform layers, and approached
      the level observed in the adult dog. Menadione-linked alpha-GPDH (M-alpha-GPDH)
      activity, however, was prominent in developing vasculature and outermost portion
      of the neuroblastic layer of the 1 day-old retina. Most notable was localization
      in vascular precursors, angioblasts, found distant from formed vessels in the
      peripheral nerve fiber layer. Retinal dependence on an oxidative metabolism in
      neuronal elements, as represented by SDH activity, occurs only when the
      vasculature is well established.

PMID- 8529420
TI  - Immunohistochemical analysis of unsutured and sutured corneal wound healing.
AB  - In the unsutured partial thickness penetrating wounds of the cornea, the
      epithelium migrates over the wounded stromal surface prior to the onset of
      stromal regeneration. To determine the possible affects of the epithelial
      ingrowth on the organization of the stromal scar tissues, the healing of
      unsutured and sutured wounds was compared immunohistochemically. Immunostaining
      patterns for fibronectin, types III, VI and VII collagen, keratan sulfate
      proteoglycan (KSPG), and intermediate filament-associated protein (IFAP 130) in
      fibroblasts, were analyzed in unsutured and adjacent sutured keratotomy wounds in
      monkeys, at 2-9 weeks after surgery. At 2-4 weeks, fibronectin, type III and type
      VI collagen showed a lamellar interweaving pattern across unsutured wounds that
      was absent in sutured wounds. Type VII collagen was detected along the entire
      depth of regenerated stroma in unsutured wounds, but not in sutured wounds
      indicating that the epithelium had formerly been present in the regenerated
      stroma in unsutured wounds. Fibroblasts in both types of wounds expressed IFAP
      130, but staining was more pronounced in sutured wounds. At 5-9 weeks, cellular
      re-activation, as judged from the expression for IFAP 130, was concomitant with a
      loss of lamellar interweaving with fibronectin, type III and type VI collagen
      across unsutured wounds, and proceeded in a posterior to anterior direction. In
      contrast, in sutured wounds, lamellar interweaving was established in anterior to
      posterior direction. At all postoperative times, unsutured and sutured wounds
      showed minimal staining for KSPG in the anterior scar.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8529422
TI  - Irritation of the anterior segment of the eye by ultraviolet radiation: influence
      of nerve blockade and calcium antagonists.
AB  - The aim of this investigation was to determine the influence on anterior segment
      inflammation elicited by UV radiation, of ocular denervation and pharmacological
      blockade of sensory nerve fibers with capsaicin, tetrodotoxin and calcium
      antagonists. Both eyes of pigmented rabbits were exposed for 5 min to UV
      radiation (254 nm); 24 h later, inflammatory signs were evaluated by
      biomicroscopy of the corneal epithelium, the stroma and the endothelium and
      scored from 0 to 4. Conjunctival vasodilation and miosis were also assessed. Two
      weeks before UV exposure, a group of rabbits received a retrobulbar injection of
      ethanol or of 1% capsaicin. Intact, capsaicin-treated and alcohol-denervated
      animals were treated topically, prior to UV exposure, with tetrodotoxin (0.78 mM)
      and the calcium antagonists diltiazem (1-28 mM) and nifedipine (10 mM). UV
      radiation produced at 24 h signs of corneal irritation, conjunctival hyperemia,
      miosis and elevated protein content of the aqueous humor. Retrobulbar injection
      of 99% alcohol or 1% capsaicin did not diminish significantly the inflammation of
      tissues directly exposed to UV radiation, although extension of inflammatory
      signs to unaffected areas was prevented. Pre-treatment of normal and denervated
      eyes with diltiazem attenuated UV-induced eye irritation signs at concentrations
      of 10 mM or over. The effect was less pronounced with tetrodotoxin and was not
      obtained with nifedipine. These findings suggest that the contribution of a
      neurogenic mechanism to anterior segment inflammation induced by UV exposure is
      modest. They also show that high concentrations of diltiazem, but not of
      nifedipine, effectively reduced inflammation of the anterior segment of the eye
      evoked by UV radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529423
TI  - Identification of the in vivo truncation sites at the C-terminal region of alpha
      A crystallin from aged bovine and human lens.
AB  - Total alpha-A crystallin was purified from young versus old lens, followed by
      digestion with cyanogen bromide. Laser desorption mass spectrometry of the C
      terminal fragment demonstrated age-dependent loss of one and five amino acids
      from the C-terminus of alpha-A crystallin from both bovine and human lens. These
      results demonstrate specific peptide bonds of alpha-A crystallin are cleaved
      during the aging process of the normal lens. The C-terminal region is cleaved in
      two places between the two hydroxyl-containing amino acids present in the
      sequence -P-S(T)-S-.

PMID- 8529424
TI  - Cyclic AMP-dependent up-regulation of the taurine transporter in a human retinal
      pigment epithelial cell line.
AB  - This investigation was undertaken to study the role of cAMP in the regulation of
      the taurine transporter expressed in a human retinal pigment epithelial (HRPE)
      cell line. Treatment of the HRPE cells with cholera toxin for 24 h was found to
      stimulate the taurine transporter activity, as measured by taurine transport into
      the cells in the presence of NaCl, to a significant extent. The stimulation was
      50-60% at 100 ng/ml cholera toxin. This stimulation was specific to the taurine
      transporter since the transport of two other amino acids (leucine and alanine),
      which are not substrates for the taurine transporter, was not affected by cholera
      toxin under similar conditions. Exposure of the cells to cholera toxin for a time
      period > 4 h was needed to elicit the stimulatory effect. The cholera toxin
      induced stimulation of the taurine transporter activity was associated with an
      increase in the maximal velocity of the transport system. The affinity of the
      transporter for taurine was not altered by the treatment. The stimulatory effect
      was markedly blunted when the treatment of the cells with cholera toxin was done
      in the presence of actinomycin D, an inhibitor of transcription, or
      cycloheximide, an inhibitor of translation. The increase in the taurine
      transporter activity induced by cholera toxin was associated with a 2.6-fold
      increase in the steady state levels of the transporter mRNA. Measurement of
      cyclic nucleotides in control and cholera toxin-treated cells revealed that the
      toxin caused a 20-fold increase in the cellular levels of cAMP, the levels of
      cGMP remaining unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529425
TI  - Membrane-associated inositol hexakisphosphate binding in bovine retina.
AB  - We investigated the InsP6 binding proteins in bovine retinal membranes and rod
      outer segments (ROS) by radioligand binding assay and western blotting. The
      relative affinity of InsP6 for the binding protein was determined by competitive
      binding of [3H]-InsP6 with increasing concentrations of the unlabeled InsP6 or
      other isomers. InsP6 specifically binds to both bovine retinal membranes and ROS;
      maximum binding was achieved after one-hour incubation at 4 degrees C and was
      unchanged up to 2 h. Tris-HCl or acetate buffer was equally suitable for the
      binding assay over a broad range of pH, although specific binding was slightly
      increased at acidic pH. The order of potencies of displacement was InsP6 >
      Ins(1,3,4,5,6)P5 > Ins(1,3,4,6)P4 = Ins(1,3,4,5)P4, whereas Ins(1,4,5)P3,
      Ins(1,4)P2, Ins(4,5)P2, and Ins(1)P were not effective displacers. Scatchard
      analyses of the binding data were consistent with an equilibrium dissociation
      constant (Kd) of 2.5 +/- 0.2 microM and maximal binding capacity (Bmax) of 123.7
      +/- 25.0 pmol/mg at pH 7.4. Western blotting was used to detect whether AP-2 (an
      InsP6 binding protein) is present in the retina. Immunoreactivity to AP-2 alpha
      and beta subunits was found in retinal membranes and ROS. Thus, bovine retinal
      membranes and ROS contain membrane-associated InsP6 binding protein(s) which is
      distinct from proteins that bind InsP5, InsP4, or InsP3.

PMID- 8529426
TI  - Immunotolerance and prevention of ocular autoimmune disease.
AB  - Immunotherapeutic approaches to autoimmune disease have a common goal of inducing
      antigen-specific, long-lasting tolerance to autoantigens, without otherwise
      compromising the immune response. Here we review some of the most interesting
      experimental advances in this area. We discuss the use of T cell targeting drugs
      that have been reported to induce long lasting tolerance to ocular antigens.
      Strategies involving the targeting of idiotypic and clonotypic determinants
      associated with ocular autoimmunity, such as idiotypic network manipulation and T
      cell vaccination, are reviewed. The use of cytokines to promote perturbation of
      the Th1/Th2 balance with its possible implications for treatment of uveitis, is
      analysed. Finally, we review tolerogenic strategies based on acquisition of
      tolerance following presentation of antigen through alternative routes, such as
      injection of antigen into the anterior chamber, intravenous infusion of antigen,
      and oral administration of retinal antigens. Special emphasis is placed on the
      last strategy, since there are ongoing clinical trials using oral tolerance as an
      immunotherapeutic approach to treat autoimmune diseases, among them uveitis.

PMID- 8529427
TI  - The distribution of fibronectin and P component in Descemet's membrane: an
      immunoelectron microscopic study.
AB  - Descemet's membrane consists of two zones, the 'anterior banded zone' which
      contains wide-spaced collagen and the amorphous 'posterior non-banded zone'. It
      is attached anteriorly to the corneal stroma by a narrow transitional zone termed
      the 'interfacial matrix'. The distribution of fibronectin and P component within
      the different layers of Descemet's membrane was investigated using an
      ultrastructural immunogold technique. Seven normal human corneas from an eye bank
      and one specimen from an orbital exenteration were examined. Fibronectin was
      predominantly present in the posterior part of the posterior non-banded zone and
      in the anterior banded zone. The anterior part of the posterior non-banded zone
      contained less fibronectin. P component was present throughout the anterior
      banded and posterior non-banded zones. There was a sharp demarcation at the
      interfacial matrix since neither substance was observed in the corneal stroma.
      The differences shown in the distribution of fibronectin and P component within
      Descemet's membrane may have resulted from their binding to other substances or
      alternatively from differences in the quantities laid down during the evolution
      of this basement membrane.

PMID- 8529428
TI  - Intravascular stents: current applications.

PMID- 8529429
TI  - Comprehensive management of infants with gastroesophageal reflux and failure to
      thrive.

PMID- 8529430
TI  - Cholesterol screening in children.

PMID- 8529431
TI  - Concentration of cephalosporins in tissues of the head and neck after parenteral
      infusion.
AB  - Cephalosporins are successfully used in the therapy of acute sinusitis, purulent
      parotitis, and lymphadenitis. Anti-infectious prophylaxis in major head and neck
      surgery may be performed with cephalosporins as first choice. For sufficient
      prophylaxis or therapy, an effective level of the antibiotic drug in the serum
      and tissue of the target organs is necessary. In a comparative investigation, we
      measured serum and tissue levels of three regions of the head and neck (parotid
      glands, paranasal sinuses, soft tissue of the neck) of the second-generation
      cephalosporins, cefuroxime and cefotiam, after a single parenteral infusion. Both
      antibiotics reach levels which are effective against bacteria typically causing
      spontaneous or postoperative infection of head and neck tissue. Effective levels
      of cefuroxime both at the investigated tissue sites and in serum are greater than
      those of cefotiam, and cefuroxime is eliminated from serum less rapidly. The
      pharmacologic data show that both drugs are suitable for therapy and
      perioperative prophylaxis of purulent head and neck infections, but various data
      indicate that there is an advantage in favor of cefuroxime.

PMID- 8529432
TI  - Antibacterial activity of cefprozil in vitro.
AB  - Cefprozil is a new orally active cephalosporin which is undergoing in vitro and
      in vivo evaluations. Using the standard agar dilution method we compared the in
      vitro activity of this drug with other oral cephalosporins and ciprofloxacin
      against 637 recent clinical isolates from the Kaohsiung Veterans General
      Hospital, Taiwan. Against Escherichia coli and Klebsiella pneumoniae, cefprozil
      showed good activity, inhibiting over 80% of these isolates at 8 mg/l. Like other
      oral drugs of its class, it had little activity against Pseudomonas aeruginosa
      and Acinetobacter spp. Against Haemophilus influenzae, irrespective of beta
      lactamase production, its activity was similar to comparable drugs. Against
      methicillin-susceptible Staphylococcus aureus, cefprozil showed high activity,
      inhibiting 90% of these isolates at 4 mg/l, whereas against methicillin-resistant
      S. aureus, its activity was higher than that of other oral cephalosporins tested
      and was similar to that of ciprofloxacin. Of enterococci tested, 57.7% were
      inhibited by 8 mg/l of cefprozil. Against beta-hemolytic streptococci, its
      activity was superior to all other drugs tested. The results of this in vitro
      study indicate that oral administration of cefprozil might be efficacious in the
      treatment of community-acquired cutaneous, respiratory and urinary tract
      infections.

PMID- 8529433
TI  - Postantibiotic effect of imipenem, alone and in combination with amikacin, on
      Pseudomonas aeruginosa.
AB  - Imipenem and amikacin, alone and in combination, were investigated for their
      postantibiotic effect (PAE) on Pseudomonas aeruginosa. Four clinical strains of
      P. aeruginosa in the logarithmic phase of growth were exposed for 1 h to
      antibiotics, alone and in combination. Recovery periods of test cultures were
      evaluated after dilution using viable counting. Imipenem produced a PAE ranging
      from 0.7 to 1.55 h. Similar PAEs were induced by amikacin (ranging from 0.65 to 2
      h). In combination, imipenem and amikacin produced as a final PAE (ranging from
      1.6 to 2.65 h), a rough mathematical sum of the individual effects. The finding
      of this study may have important implications for the timing of doses during
      therapy with antimicrobial combinations.

PMID- 8529434
TI  - Comparison of Wilkins-Chalgren medium supplemented with nicotinamide adenine
      dinucleotide and Haemophilus test medium for susceptibility testing of clinical
      Haemophilus isolates.
AB  - Haemophilus test medium (HTM) was compared with Wilkins-Chalgren agar (WCA;
      supplemented with 15 micrograms/ml nicotinamide adenine dinucleotide (NAD)) for
      antibiotic susceptibility testing of 74 clinical isolates of Haemophilus
      influenzae and Haemophilus parainfluenzae. The Bauer-Kirby agar disk diffusion
      method and the agar dilution procedure were the two tests employed. WCA + NAD and
      HTM yielded comparable results for the following antimicrobial drugs and drug
      combinations: ampicillin, amoxicillin plus clavulanic acid, ampicillin plus
      sulbactam, cefotaxime, cefuroxime, chloramphenicol, ciprofloxacin, and
      doxycycline. However, WCA + NAD slightly antagonized rifampin. Co-trimoxazole was
      significantly antagonized by WCA + NAD. WCA + NAD was much simpler with regard to
      in-house preparation, and WCA plates could be supplemented with NAD following
      pouring, solidification and storage of the plates simply by surface spreading the
      required amount of NAD with a glass spatula, thus adding considerably to
      laboratory flexibility. It is suggested that additional laboratories
      comparatively and critically examine WCA + NAD medium for antibiotic
      susceptibility testing of clinical Haemophilus isolates.

PMID- 8529435
TI  - Effect of desferrioxamine on cisplatin-induced nephrotoxicity in normal rats.
AB  - Biochemical and histological evaluations of the effects of the iron chelator
      desferrioxamine on the nephrotoxicity induced by cisplatin in normal rats were
      carried out. A single dose of cisplatin (7.5 mg/kg, intravenously) caused
      nephrotoxicity that manifested biochemically as an elevation of blood urea
      nitrogen, serum creatinine and an increase in the kidney weight as a percent of
      body weight. Moreover, severe decreases in serum calcium and albumin were
      observed. Histopathological examination of kidney tissue revealed tubular
      necrosis with sloughing of tubular epithelium. Desferrioxamine treatment (250
      mg/kg, intraperitoneally) 30 min before cisplatin administration does not protect
      the kidney from the damaging effects of cisplatin. A greater increase in blood
      urea nitrogen, serum creatinine and kidney weight was observed with significant
      tubular necrosis and a mild lymphocytic infiltrate. Desferrioxamine pretreatment
      decreased the lipid peroxidation induced by cisplatin but at the same time
      increased nonprotein sulfhydryl (-SH) concentrations in the kidney tissue. The
      findings of this study suggest that lipid peroxidation is not the main cause of
      cisplatin-induced nephrotoxicity and that desferrioxamine which was useful for
      prevention of cardiac and hematological damage induced by doxorubicin, aggrevated
      the cisplatin-induced nephrotoxicity. More investigations are needed to establish
      a definite assessment of its selectivity.

PMID- 8529436
TI  - In vitro and in vivo sensitivity of a non-mouse-adapted influenza A (Beijing)
      virus infection to amantadine and ribavirin.
AB  - A clinically isolated non-mouse-adapted influenza A/Beijing/32/92 virus was
      assayed for sensitivity to amantadine and ribavirin in vitro and in mice. When
      multiple concentrations of each drug were assayed for ability to inhibit the
      virus-induced cytopathic effect in MDCK cells, the 50% effective (virus
      inhibitory) concentration was 0.12 microgram/ml for amantadine and 1.9
      micrograms/ml for ribavirin. The 50% cytotoxic concentrations were 25 and 100
      micrograms/ml, respectively. It is known that intranasal challenge of mice with
      high concentrations of non-mouse-adapted influenza virus will induce a toxic
      pneumonitis in the absence of significant viral replication in the lung.
      Treatment of such virus-infected mice with approximately 1,250, approximately 625
      and approximately 313 mg/kg/day of amantadine in the drinking water resulted in
      significant inhibition of lung scores and weights and a lessened decline in
      arterial oxygen saturation (SaO2) in the mice, but virus was in low titer or not
      recoverable from drug- or placebo-treated animals. Intraperitoneal treatment with
      75, 37.5 and 18.8 mg/kg/day of ribavirin given twice daily for 5 days was
      effective only in preventing SaO2 decline, which contrasts with strong inhibition
      of infections induced by mouse-adapted viruses seen in other studies. These in
      vivo data indicate that when non-mouse-adapted influenza virus infections are
      used to evaluate potential antiviral drugs, false-negative results may be
      obtained.

PMID- 8529437
TI  - The administration regimen of isepamicin in patients with chronic respiratory
      tract infection.
AB  - A total of 34 patients with intractable chronic respiratory tract infections were
      treated with isepamicin and/or piperacillin in different dosage regimens. A
      comparison of the bacteriological effect using a cross over method showed a
      reduction in the count of Pseudomonas aeruginosa in sputum in the group receiving
      once-a-day isepamicin combined with piperacillin, compared with the twice-a-day
      combined administration. A comparison of the clinical and bacteriological
      efficacy between the different regimen groups revealed no noticeable difference.
      The clinical effect of this regimen is comparable to the conventional regimen,
      but has the advantages of a safer dosage and ease of administration.

PMID- 8529438
TI  - Tumor lysis syndrome following single-dose mitoxantrone.
AB  - We report here a 16-year-old boy with pre-B-type acute lymphoblastic leukemia who
      developed acute tumor lysis syndrome (TLS) following 12 h mitoxantrone infusion.
      TLS is a distinct clinical entity which has been recognized most frequently with
      aggressive combination chemotherapy of rapidly proliferating hematologic
      neoplasms. There have been a few reports of single-agent-induced tumor lysis, but
      to our knowledge, this is the first case reported with mitoxantrone alone.

PMID- 8529439
TI  - Amphotericin B lipid complex to treat invasive fungal infections in cancer
      patients: report of efficacy and safety in 20 patients.
AB  - 20 patients with proven or suspected fungal infections were treated with the
      amphotericin B lipid complex (ABLC) with a daily dose of 5 mg/kg for 1-25 days. 6
      patients died during the therapy due to fungal infection (3) or underlying
      disease (3). One patient was not evaluable. 13 patients were cured and improved.
      ABLC was administered in patients with renal disease avoiding the use of
      conventional amphotericin B (AmB) because of nephrotoxicity or after failure with
      AmB. Except for hypokalemia persisting after AmB in 5 patients, no systemic
      adverse reaction appeared. ABLC is a promising, well-tolerated and effective drug
      for the therapy of fungal infections after the failure of a previous antifungal
      therapy or after toxic reactions due to AmB.

PMID- 8529440
TI  - A multicenter comparative study of the in vitro activity of fleroxacin and other
      antimicrobial agents.
AB  - The in vitro activity of fleroxacin was determined by broth microdilution against
      2,079 recent bacterial isolates and compared to the activities of ciprofloxacin,
      ofloxacin, lomefloxacin, cefaclor, cefuroxime, cefixime, ceftriaxone,
      amoxicillin/clavulanate, trimethoprim/sulfamethoxazole (TMP-SMX), and, as
      appropriate, erythromycin and oxacillin. Most Enterobacteriaceae were inhibited
      by the quinolones at a concentration of < or = 1 microgram/ml; MIC90s of
      fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin were 0.25, 0.5, 1 and 1
      micrograms/ml, respectively. Fleroxacin was 2-fold more active than ciprofloxacin
      against Providencia stuartii and Serratia marcescens. Aside from the quinolones,
      ceftriaxone and TMP-SMX were the most active antibiotics against the
      Enterobacteriaceae, with MIC90s of 8 and 16 micrograms/ml, respectively.
      Ciprofloxacin was more active against Pseudomonas aeruginosa than the other
      quinolones, while fleroxacin was more active against Stenotrophomonas
      maltophilia: 17.7, 11.2, 20.0, and 22.4% of P. aeruginosa were resistant to
      fleroxacin, ciprofloxacin, ofloxacin, and lomefloxacin, respectively. Moraxella
      catarrhalis and Haemophilus influenzae were uniformally susceptible to all
      antibiotics tested, as were the majority of oxacillin-susceptible staphylococci.
      The MIC90s of the quinolones and of the beta-lactam antibiotics for oxacillin
      resistant staphylococci were 8- to 256-fold higher than for oxacillin-susceptible
      staphylococci. The beta-lactam antibiotics, TMP-SMX, and erythromycin were more
      active than the quinolones against streptococci; all antibiotics were poorly
      active against enterococci. Fleroxacin is active against a broad range of gram
      negative bacilli and against oxacillin-susceptible staphylococci and should prove
      useful for such infections. However, its use cannot be recommended for infections
      due to oxacillin-resistant staphylococci, streptococci, or enterococci.

PMID- 8529441
TI  - [1994 German Federal Health Insurance Ordinance prerequisites for implementation
      starting 1 January 1996].

PMID- 8529442
TI  - [Surgical therapy of soft tissue sarcomas II. Sarcomas of the extremities and
      their surgical resection].
AB  - In the past, the rate of amputation for soft tissue sarcomas of the extremities
      was 40-50%. In recent years this rate has declined to about 50%. The improved
      rate of limb salvage with improved rates of local control, compared to those of
      the past, has been due to the development of surgical techniques allowing often
      satisfactory resection with limb preservation and to the use of adjuvant
      radiation in the presence of inadequate surgical margins. Below, the surgical
      techniques of limb preservation, as well as those or the major amputations are
      described.

PMID- 8529443
TI  - [Atopic stomach polyp as the cause of invagination of Meckel's diverticulum].
AB  - We report a 16 year old boy with suspected appendicitis. Besides leucocytosis a
      roll was palpable in the right lower quadrant. The enema with water soluble
      contrast medium revealed an invagination. Intraoperatively, reduction was
      possible. The cause was an inverted Meckel's diverticulum. In this diverticulum
      we found a large perpendicular hyperplasiogenic gastric polyp as the cause of
      inversion and invagination.

PMID- 8529444
TI  - [Differentiated thyroid gland carcinomas in "autonomous adenomas" in childhood].
AB  - Thyroid surgery is seldomly indicated in childhood and adolescence mainly because
      of suspicious nodules or proven carcinoma. Indications for operation in Graves
      disease and focal autonomy are discussed controversially, however. In a
      retrospective case control study two of our 6 patients up to 18 years
      demonstrated differentiated thyroid cancer with focal autonomy in the autonomous
      nodule. Other studies show similar results. Thyroid surgery is therefore
      warranted in all children and adolescents with focal thyroid autonomy.

PMID- 8529445
TI  - [Sacral recurrence of rectal carcinoma].
AB  - The records and operation reports of 101 patients (52 male, 49 female) with
      locally recurrent rectal cancer treated between 1980 and 1994 were reviewed. 72%
      of these patients were symptomatic at the time of diagnosis. 51 patients were
      operated on with curative intent (16 with IORT), whereas 26 underwent palliative
      surgical resection. Multivisceral resection was performed in 62.3%. In 24
      patients with recurrent tumors (11 with exploratory celiotomy) no major surgical
      resection was considered indicated. The operative mortality rate was 1.1%. 48
      complications occurred in 32 patients with exploratory celiotomy resulting in a
      36.3% morbidity rate. In the curative group partial or complete pain relief was
      achieved in 81%, whereas 75% of those in the palliative group had pain control.
      The median survival was 24 months for the curative group and 17 months for the
      group with microscopic or gros residual disease (p < 0.05). Initial inoperability
      resulted in a median life expectancy of 7 months. The 5-year survival was 13.5%
      for the group with surgical resection and 21% for patients with curative
      resection (n = 51). Actuarial 5-year survival for patients who received IORT (n =
      16) was 27%, compared with 17% for those (n = 35) who did not (p > 0.05) and
      respective local tumor control were 50% and 34% (p > 0.05). We conclude that
      radical resection of tumor recurrence in the pelvis can be performed with
      acceptable mortality and morbidity, palliates local complaints and offers
      excellent local control and survival in patients who can undergo complete
      resections with negative margins.

PMID- 8529446
TI  - [Abdominal recurrence after interventions on the intestines].
AB  - Local recurrences (LR) of intestinal tumors have to be divided into intra- and
      extraluminal LR since operative reintervention is more frequently possible in
      intraluminal tumor recurrences. Esophageal cancer most frequently recurs in the
      posterior mediastine and in the neck. In our own patients we found 16% LR
      following curative esophagectomy. Curative reresection is normally not possible.
      Palliative treatment aims to maintain the passage of food. In gastric cancer LR
      is most frequently seen following resection of a diffuse type carcinoma. The
      incidence of 7,8% in our series is low. Curative reresection was possible in 19%
      of extraluminal LR and in 75% of intraluminal LR. Colon carcinoma usually recurs
      in the abdomen. 12% of left sided primary tumors recur in the pelvis. Quite
      frequently extended multivisceral resections are necessary to deal with the LR.
      In 69% reresection was possible and in 41.5% R0-resection was achieved. As in
      gastric cancer intraluminal LR tend to have a better prognosis. The decision for
      operative reintervention has to take individual risk factors into consideration.

PMID- 8529447
TI  - [Resections of recurrence in the liver of primary and secondary liver cancers].
AB  - 1) Only one third of primary hepatic carcinomas and in particular hepatocellular
      carcinomas are amenable to liver resection. Approximately half of these patients
      develop tumor recurrences within the first two years accounting for the poor
      prognosis of this condition. The liver is the site of first failure in about 80
      percent of patients. Secondary liver surgery for intrahepatic recurrence is
      technically possible in about one third of the patients at low operative
      mortality (< 5 percent). Long-term prognosis following potentially curative liver
      reresection for hepatosellular carwinoma compares favourably (5-year survival
      approximately 50 percent) with the prognosis after resection of the primary
      tumor. For potentially curative treatment liver transplantation is the only
      alternative to hepatic reresection, while alcohol injection and chemoembolization
      are merely palliative procedures. II) Liver resection represents the only
      potentially curative form of treatment for hepatic metastases from collorectal
      cancer. Operative mortality is generally less than 5 percent and 5-year survival
      of 20-40 percent can be expected. Secondary hepatic recurrences following hepatic
      resection of colorectal metastases are amenable to reresection in approximately
      10 percent of patients. Selection criteria for reresection are the same as for
      primary liver reresection. Median survival following secondary liver resection is
      32 months and this is identical to the median survival after the first liver
      resection for colorectal metastases.

PMID- 8529448
TI  - [Recurrent tumor after R0 resection of colorectal liver metastases. Incidence,
      resectability and prognosis].
AB  - In the period 1960 to 1992 a total of 366 patients underwent macroscopic and
      histologic complete resection (R0) of colorectal liver metastases. Excluding 16
      operative deaths and 4 patients with incomplete follow-up information, 346
      patients form the basis for this report. Of them, 240 (69.4%) developed recurrent
      disease involving the liver in 136 (39.3%) instances. 71 patients underwent a
      tumor related reoperation with a re-resection performed in 60 cases. This
      involved the liver in 22 patients. 47 of these procedures (19.6% of all
      recurrences), and 16 re-resections of the liver (11.8% of hepatic recurrences)
      were ultimately classified R0. Additional 9 patients who had the initial liver
      resection performed in other hospitals underwent hepatic re-resection which was
      classified R0 in 8. Out of 8 subsequent reoperations, 3 addressed the liver.
      Operative mortality in the 34 re-resections at the liver was 2.9% while nonlethal
      morbidity was 17.7%. After a minimum and median follow-up time of 18 and 49
      months, resp., 27 patients are alive without recurrent disease, including 11
      patients with hepatic re-resection. Another 4 patients are alive with disease,
      one of them after repeat liver resection. 5-year survival from re-resection is
      39.0% for the entire group of 55 R0-patients, and 45.6% for the 24 who underwent
      hepatic R0-re-resection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529449
TI  - [What is the role of the pubococcygeal and puborectal muscles in patients with
      obstructive defecation disorders? An electromyography study].
AB  - BACKGROUND: We believe that the M. levator ani plays little or no role in
      obstructed defaecation, and that the concept of "paradoxical" puborectalis muscle
      activity is misleading. The main aim of the study was to investigate the function
      of the pubococcygeal muscle during simulated defaecation and to compare this with
      the electromyographic activity of the puborectal muscle. METHODS AND RESULTS: In
      a prospective electromyographic study of 18 women (average age 53 years) with
      obstructive defecation disorder the activity of the pubococcygeal muscle and the
      puborectal muscle was investigated at rest, during contraction and straining. The
      control group consisted of 18 healthy women with an average age of 54 years. The
      function of the pubococcygeal muscle and the puborectal muscle was largely the
      same in both, study and control group. No statistically significant differences
      in the amplitude were found between the two groups at rest during contraction and
      maximum strain. CONCLUSION: We therefore conclude that the increase in activity
      of the voluntary muscle of the pelvic floor observed on electromyography during
      defaecation does not indicate automatically a pathologic condition but is a
      possible functional state at this moment.

PMID- 8529450
TI  - [Follow-up results of laparoscopic cholecystectomy].
AB  - Following a laparoscopic cholecystectomy 400 patients have been interviewed with
      a questionnaire on the late results of the surgery (15 to 40 months postop.). The
      cholecystectomies had been performed within the time from March 7, 1990 to April
      30, 1992 in Tubingen. After a mean of 16.8 days the patients returned to work,
      while they themselves felt reduced for an average of 10.6 days. 11.9% of the
      patients complained of slight wound healing problems and in 3.1% wound infections
      have been registered. Although 97% of the patients were satisfied with the
      results of surgery, 8.7% still complained of upper abdominal trouble. Slight
      persistent problems like light pain or flatulence have been reported by 19%.

PMID- 8529451
TI  - [Does the "Bergetrokar" decrease the rate of intraoperative complications in
      laparoscopic cholecystectomy?].
AB  - Several international surveys have proved the laparoscopic cholecystectomy as a
      safe surgical technique. In spite of the good results there still exist operation
      specific technical problems. The perforation of the gallbladder during dissection
      or while extracting it from the abdominal cavity can lead to severe
      complications. We analysed retrospectively 352 extractions of the gallbladder
      carried out with our 'Bergetrokar'. In 1.4% occurred perforation of the
      gallbladder and in 0.85% we had trouble with the healing. In 3.5% extraction
      could not be performed with the 'Bergetrokar'. Regarding these results our rates
      have been lower as compared in literature. In our opinion the extraction of the
      gallbladder through the lateral incision using the Bergetrokar represents a
      further step toward a safe extraction of the stonefilled gallbladder. Further the
      infection rate at the umbilical incision is reduced.

PMID- 8529452
TI  - [Thoracoscopic operation of secondary spontaneous pneumothorax].
AB  - Since January 1990 we have treated 49 patients with spontaneous pneumothorax (35
      primary and 14 secondary cases) by thoracoscopic operation. All patients entered
      a prospective trial. Those with secondary pneumothorax are discussed here. There
      have been no major complications. Conversion rate however has been high with 4/14
      (29%). Three more patients (21%) not suitable for thoracotomy suffered from
      persistent air leaks. The other 7 patients needed postoperative drainage for less
      than 6 days in average. VATS could nevertheless be an alternative to thoracotomy
      for avoiding prolonged suction treatment in patients with secondary pneumothorax
      as patients showed no complications or disadvantage after conversion to
      thoracotomy.

PMID- 8529453
TI  - [Desmoid tumors in patients with familial adenomatous polyposis (FAP). Clinical
      and therapeutic observations from the Heidelberg polyposis register].
AB  - The life-threatening event of early colorectal cancer in FAP patients may
      effectively be prevented by prophylactic colectomy. Desmoid tumors and
      periampullary carcinoma are now becoming the most frequent causes of death in FAP
      patients. Since the establishment of the Heidelberg polyposis registry in January
      1991 we evaluated the frequency of desmoid tumors in 171 prospectively reexamined
      FAP patients. 29 patients (17%) with desmoid tumors were identified. In our
      series R0-resection with a wide security margin was performed in 12 cases, 3 of
      which developed a desmoid recurrence, 8 are free of desmoids and one treated for
      an intraabdominal desmoid states being well but refuses a radiological
      reevaluation. Tumor debulking was performed in 6 patients and led to an
      aggressive desmoid progression in 4 patients despite additional postoperative
      administration of tamoxifen and sulindac. Nonsurgical treatment with tamoxifen
      and sulindac seemed beneficial in 5 of 7 patients, 4 showed a stagnation of tumor
      growth, a reduction of an abdominal wall desmoid was documented in one female
      with a further intraabdominal desmoid. In life-threatening cases chemotherapy and
      radiation therapy may be considered. In two females radiation therapy resulted in
      a remarkable tumor reduction. The operative trauma of previous colectomy is
      considered the most relevant predisposing external factor inducing desmoid growth
      in FAP patients. 50% (11/22) of the desmoid tumors in our series were diagnosed
      within the first two years postoperatively, and 72% (18/22) of the desmoids
      developed within the first four years after colectomy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8529454
TI  - A change in the phosphorylation pattern of the 30000-33000 Mr synaptonemal
      complex proteins of the rat between early and mid-pachytene.
AB  - The lateral elements (LEs) of synaptonemal complexes (SCs) of the rat contain
      major components with relative electrophoretic mobilities (Mr s) of 30000-33000,
      which are the products of a single gene. After one-dimensional separation of SC
      proteins on polyacrylamide-SDS gels, these components show up as two major bands,
      whereas upon two-dimensional electrophoresis they are resolved in at least 24
      spots, which focus at pH 6.5 to 9.5. In this paper we show that these spots
      represent phosphorylation variants. For the analysis of the phosphorylation of
      the 30000- to 33000-Mr SC components during progression through meiotic prophase,
      we developed a procedure for isolation of fractions of testicular cells of the
      rat that are enriched in separate stages of meiotic prophase. Analysis of the
      30000- to 33000-Mr SC components in these fractions by two-dimensional
      electrophoresis and immunoblotting showed that phosphorylated variants of the
      30000- to 33000-Mr SC proteins occur throughout meiotic prophase. However, the
      extent of phosphorylation changes between early and mid-pachytene, when one
      phosphate group is probably added to each of the variants.

PMID- 8529455
TI  - Genetic control of synapsis and recombination in Lolium amphidiploids.
AB  - Homologous bivalent formation in amphidiploids of Lolium is promoted during
      meiosis by diploidising genes carried by A-chromosomes, and by supernumerary B
      chromosomes. The site and mode of action of these diploidising factors were
      investigated by comparing the relative frequencies of pairing configurations at
      meiotic prophase and metaphase I in several different hybrid genotypes. The
      results indicate that diploidising genes act predominantly by increasing the
      stringency of synapsis at early stages of meiotic prophase. By contrast, B
      chromosomes appear to promote bivalent formation by ensuring that homoeologously
      paired chromosome segments within multivalents do not crossover. The results show
      that the additive effects of diploidising genes and B-chromosomes are to a
      certain extent separable in terms of their mode of action and timing during
      meiosis.

PMID- 8529456
TI  - Histones H1 and H4 of surface-spread meiotic chromosomes.
AB  - The chromatin conformation of somatic and meiotic chromosomes is, at least in
      part, a function of electrostatic nucleosome interactions that are mediated by
      transient acetylation of the histone H4 N-terminal domain and phosphorylation of
      histone H1. The distribution of those histones in the chromatin of meiotic
      chromosomes is reported here. Antibodies to testis-specific histone 1, H1t,
      detect H1t in the chromatin of mouse meiotic prophase chromosomes only after
      synapsis and synaptonemal complex (SC) assembly is completed and before core
      separation is initiated. The H1t protein is evenly distributed over euchromatin,
      heterochromatin and the SC. Antibodies to acetylated lysine residues 5, 12 or 16
      of histone H4, indicate that the euchromatin is more acetylated than the
      centromeric heterochromatin. The pattern is most pronounced for acetylated
      residue 5 and least for 16. Antibodies to phosphorylated H1 epitopes do not react
      with chromatin but, instead, recognize the chromosome cores and SCs. Possibly
      these are not phosphorylated histone H1 epitopes, but SC proteins with similar
      potentially phosphorylatable sequences such as KTPTK of the synaptic protein
      Syn1.

PMID- 8529457
TI  - Immunocytology of chiasmata and chromosomal disjunction at mouse meiosis.
AB  - Immunocytological and in situ hybridization evidence supports the hypothesis that
      at meiosis of chiasmate organisms, chromosomal disjunction and reductional
      segregation of sister centromeres are integrated with synaptonemal complex
      functions. The Mr 125,000 synaptic protein, Syn1, present between cores of paired
      homologous chromosomes during pachytene of meiotic prophase, is lost from
      synaptonemal complexes coordinately with homolog separation at diplotene.
      Separation is constrained by exchanges between non-sister chromatids, the
      chiasmata. We show that the Mr 30,000 chromosomal core protein, Cor1, associated
      with sister chromatid pairs, remains an axial component of post-pachytene
      chromosomes until metaphase I. We demonstrate that at this time the chromatin
      loops are still attached to their cores. A reciprocal exchange event between two
      homologous non-sister chromatids is therefore immobilized by anchorage of sister
      chromatids to their respective cores. Cores thus contribute to the sister
      chromatid cohesiveness required for maintenance of chiasmata and proper
      chromosomal disjunction. Cor1 protein accumulates in juxtaposition to pairs of
      sister centromeres during metaphase I. Presumably, independent movement of sister
      centromeres at anaphase I is restricted by Cor1 anchorage. That reductional
      separation of sister centromeres is mediated by Cor1, is supported by the
      dissociation of Cor1 from separating sister centromeres at anaphase II and by its
      absence from mitotic anaphases.

PMID- 8529458
TI  - Morphology of a human-derived YAC in yeast meiosis.
AB  - In meiosis of human males DNA is packaged along pachytene chromosomes about 20
      times more compactly than in meiosis of yeast. Nevertheless, a human-derived
      yeast artificial chromosome (YAC) shows the same degree of compaction of DNA as
      endogenous chromosomes in meiotic prophase nuclei of yeast. This suggests that in
      yeast meiosis, human and yeast DNA adopt a similar organization of chromatin
      along the pachytene chromosome cores. Therefore meiotic chromatin organization
      does not seem to be an inherent chromosomal property but is governed by the host
      specific cellular environment. We suggest that there is a correlation between the
      less dense DNA packaging and the increased rate of recombination that has been
      reported for human-derived YACs as compared with human DNA in its natural
      environment.

PMID- 8529459
TI  - Chromosome dynamics in rad12 mutants of Coprinus cinereus.
AB  - We have characterized the phenotypes of three rad12 mutants of the basidiomycete
      Coprinus cinereus, which were isolated on the basis of sensitivity to ionizing
      radiation. Electron microscopic studies of meiotic nuclear spreads showed that
      all three rad12 mutants are defective in chromosomal synapsis. For rad12-1 and
      rad12-4, very limited assembly of the synaptonemal complex occurs. The phenotype
      of rad12-15 is less severe and longer stretches of synapsed chromosomes are
      formed. However, for all three alleles mutant nuclei arrest in a diffuse state
      with little synaptonemal complex structure. Observations made of spreads of
      acridine orange-stained meiotic nuclei correlated with the electron microscopic
      data. In rad12 strains, chromosomes condense but do not pair, and they later
      arrest in a decondensed state; very few rad12 cells enter metaphase I. Homozygous
      dikaryons of rad12 mutants produce fruiting bodies with significantly fewer
      basidiospores than are found in wild-type dikaryons. The viability of these
      spores is greatly reduced: all spores produced by rad12-1 and rad12-4 mushrooms
      fail to germinate, while only 16% of rad12-15 spores are viable. Recombination
      within the tract of the ribosomal RNA gene repeats was not significantly
      different in the mutants when compared with a wild-type congenic control.
      Quantitative measurements of oidial survival indicate that all three rad12
      alleles are sensitive to gamma radiation but insensitive to UV radiation relative
      to wild-type strains.

PMID- 8529460
TI  - Microtubule-driven nuclear movements and linear elements as meiosis-specific
      characteristics of the fission yeasts Schizosaccharomyces versatilis and
      Schizosaccharomyces pombe.
AB  - Meiotic prophase in Schizosaccharomyces pombe is characterized by striking
      nuclear movements and the formation of linear elements along chromosomes instead
      of tripartite synaptonemal complexes. We analysed the organization of nuclei and
      microtubules in cells of fission yeasts undergoing sexual differentiation. S.
      japonicus var. versatilis and S. pombe cells were studied in parallel, taking
      advantage of the better cytology in S. versatilis. During conjugation,
      microtubules were directed towards the mating projection. These microtubules seem
      to lead the haploid nuclei together in the zygote by interaction with the spindle
      pole bodies at the nuclear periphery. After karyogamy, arrays of microtubules
      emanating from the spindle pole body of the diploid nucleus extended to both cell
      poles. The same differentiated microtubule configuration was elaborated upon
      induction of azygotic meiosis in S. pombe. The cyclic movements of the elongated
      nuclei between the cell poles is reflected by a dynamic and coordinated
      shortening and lengthening of the two microtubule arrays. When the nucleus was at
      a cell end, one array was short while the other bridged the whole cell length.
      Experiments with inhibitors showed that microtubules are required for karyogamy
      and for the elongated shape and movement of nuclei during meiotic prophase. In
      both fission yeasts the SPBs and nucleoli are at the leading ends of the moving
      nuclei. Astral and cytoplasmic microtubules were also prominent during meiotic
      divisions and sporulation. We further show that in S. versatilis the linear
      elements formed during meiotic prophase are similar to those in S. pombe.
      Tripartite synaptonemal complexes were never detected. Taken together, these
      findings suggest that S. pombe and S. versatilis share basic characteristics in
      the organization of microtubules and the structure and behaviour of nuclei during
      their meiotic cell cycle. The prominent differentiations of microtubules and
      nuclei may be involved in the pairing, recombination, and segregation of meiotic
      chromosomes.

PMID- 8529461
TI  - Identification of functional domains in the Sep1 protein (= Kem1, Xrn1), which is
      required for transition through meiotic prophase in Saccharomyces cerevisiae.
AB  - The Sep1 (also known as Kem1, Xrn1, Rar5, DST2/Stpbeta) protein of Saccharomyces
      cerevisiae is an Mr 175,000 multifunctional exonuclease with suspected roles in
      RNA turnover and in the microtubular cytoskeleton as well as in DNA recombination
      and DNA replication. The most striking phenotype of SEP1 null mutations is
      quantitative arrest during meiotic prophase at the pachytene stage. We have
      constructed a set of N- and C-terminal as well as internal deletions of the large
      SEP1 gene. Analysis of these deletion mutations on plasmids in a host carrying a
      null allele (sep1 ) revealed that at least 270 amino acids from the C-terminus of
      the wild-type protein were dispensable for complementing the slow growth and
      benomyl hypersensitivity of a null mutant. In contrast, any deletion at the N
      terminus abrogated complementing activity for these phenotypes. The sequences
      essential for function correspond remarkably well with the regions of Sep1 that
      are homologous to its Schizosaccharomyces pombe counterpart Exo2. In addition,
      these experiments showed that, despite the high intracellular levels of Sep1,
      over-expression of this protein above these levels is detrimental to the cell. We
      discuss the potential cellular roles of the Sep1 protein as a microtubule-nucleic
      acid interface protein linking its suspected function in the microtubular
      cytoskeleton with its role as a nucleic acid binding protein.

PMID- 8529462
TI  - Chiasma-based genetic map of the mouse X chromosome.
AB  - The X chromosome pair was identified in diakinesis/metaphase I stage mouse
      oocytes using a repeat sequence DNA probe and fluorescence in situ hybridisation.
      Chiasma positions along the X bivalent were measured in 57 oocytes from 4
      females. Overall, our observations showed that while there were no obvious
      "hotspots" for chiasma formation along the X chromosome, there was a tendency to
      favour the distal end. Minimum inter-chiasma distances were substantial
      indicating the occurrence of strong genetic interference. Estimates of both
      genetic distances and recombination fractions for any interval along the
      chromosome can be calculated from the chiasma data. The average chiasma frequency
      for the X bivalent was 1.37 giving an estimated total genetic map length of 68.5
      cM. In general, the pattern of chiasma distribution along the X chromosome
      resembled that anticipated from recombination distances in published consensus
      linkage maps. There were, however, some intriguing differences between the two
      approaches. The reason for these discrepancies are unknown but may be related to
      lack of precision in cytogenetic mapping of loci, inter-strain and/or
      interspecies differences in the genetic controls over the distribution of
      crossover events. One advantage of the chiasma analysis approach is its
      suitability for investigating these problems.

PMID- 8529463
TI  - Bivariate cytokeratin/DNA flow cytometric analysis of paraffin-embedded samples
      from colorectal carcinomas.
AB  - Admixture of normal and neoplastic cells is a serious problem in the evaluation
      of tumor cell kinetic parameters by flow cytometry, in particular for DNA diploid
      tumors. The admixture of non-neoplastic cells, such as stromal cells and
      inflammatory cells, can disturb the estimation of the proliferative tumor
      fraction. This problem has been addressed in fresh tumor samples by applying
      bivariate flow cytometric analyses for DNA and cytokeratin. We have adapted this
      approach for formalin-fixed and paraffin-embedded tissue samples of colorectal
      carcinomas. After preparation of a single cell suspension from paraffin blocks by
      means of an enzymatic digestion step, the cells of epithelial origin were
      selectively stained with a panel of subtype specific cytokeratin antibodies. DNA
      analysis could thus be performed on the cytokeratin-positive cells. The
      proliferative fractions of the paraffin-embedded samples could be compared with
      those of the fresh tissue samples and a very good correlation was seen between
      DNA indices from fresh and paraffin-embedded material. As expected, after gating
      on the cytokeratin-positive cells an enrichment of the S-phase fraction was seen
      compared with the ungated cell population. However, this enrichment was more
      pronounced in the cell suspensions derived from the paraffin-embedded part of the
      tumor compared with the fresh disaggregated, ethanol-fixed part of the tumor.

PMID- 8529464
TI  - Geographic distribution of co-dominant DNA stemlines in breast carcinoma.
AB  - Breast carcinomas often contain multiple DNA stemlines in flow cytometric DNA
      histograms. However, due to mixing during tissue disaggregation the
      microanatomical relationship between the cells which comprise distinct stemlines
      is unclear. We performed image cytophotometric DNA analysis (IA) on two separate
      areas of intact tissue sections of 19 breast carcinomas which were selected on
      the basis of flow cytometric (FCM) DNA content heterogeneity (i.e., multiple
      stemlines). For comparison, similar analyses were performed on seven tumors with
      unimodal FCM DNA histograms. Six of the 7 tumors (86%) with unimodal FCM
      histograms were also unimodal in both IA DNA histograms. Among tumors with
      heterogeneous FCM DNA histograms, the presence of multiple stemlines was
      confirmed in IA DNA histograms in 16/19. In nine of these 16 cases, multiple DNA
      stemlines having similar DNA indices were present in both areas of neoplasm
      examined with IA. The remaining seven cases displayed unimodal IA histograms in
      both areas, however DNA indices differed between the two histograms. These
      findings imply that cell populations corresponding to flow cytometrically
      detected DNA stemlines are often intimately admixed, even within geographically
      separated portions of breast tumors. This pattern suggests that productive
      interactions between genetically distinct tumor populations may lead to stable co
      dominance of ancestral clones during progression of some breast carcinomas.

PMID- 8529465
TI  - Assessing sequential oncogene amplification in human breast cancer.
AB  - Studies of amplification and/or overexpression of c-myc, HER-2/neu, and H-ras in
      breast cancer have shown that each is associated with a poor prognosis. The
      purpose of this study was to explore the possibility that there is a preferred
      sequence of amplification of these oncogenes in breast cancer. The frequencies of
      amplification and patterns of co-amplification of c-myc, HER-2/neu, and H-ras
      were studied in a group of 84 breast cancers. The data suggested a preferred
      sequence of amplification that consisted of c-myc amplification-HER-2/neu
      amplification-H-ras amplification. This model was supported by loglinear
      analysis. In addition, the levels of amplification of JC-A, a DNA fragment newly
      isolated from a patient with advanced breast cancer, were studied in 61 of these
      cases. The data suggested that JC-A amplification occurred early. Loglinear
      analysis supported a model in which JC-A amplification occurred either before or
      after c-myc amplification but was unrelated to Her-2/neu or ras amplification.

PMID- 8529466
TI  - Genetic and phenotypic heterogeneity of human malignancies: finding order in
      chaos.
AB  - The presence of cellular heterogeneity within human tumors has been recognized
      for many years. Current concepts regarding the clonal origin of human neoplasms,
      and recent advances in the study of successive genetic changes that occur during
      tumor evolution may now make it possible to understand in greater depth the
      biological and clinical implications of intra-tumor heterogeneity at both the
      phenotypic and genotypic levels. In order to explore these concepts further, and
      to better identify the potential contributions that flow and image cytometry can
      make to our understanding of tumor heterogeneity, a session of the 1994 ISAC
      Congress was dedicated to plenary presentations on human cancer cell
      heterogeneity. Here, we provide a brief overview of the genetic evolutionary
      progression of human cancers, some considerations of clinically important
      phenotypic and genotypic markers, and an outline that might serve as a basis for
      framing relevant issues that are ammenable to further study. All Nature is but
      Art, unknown to thee; All Chance, Direction, which thou canst not see; All
      Discord, Harmony not understood: All partial Evil, universal Good. (Alexander
      Pope, Essay on Man, end of Epistle 1).

PMID- 8529467
TI  - Analytical approaches relating genetic evolutionary pathways to prognostic
      factors.
AB  - Human solid tumors accumulate multiple genetic abnormalities as they progress to
      advanced stages. Multiparameter flow cytometry measurements of individual cells
      within each tumor may be useful in describing the genetic pathways taken by
      individual tumors during the course of their genetic evolution. In this paper, we
      analyzed correlated cell-by-cell measurements of cell DNA content, HER-2/neu
      protein content, and ras protein content obtained by multiparameter flow
      cytometry studies of primary breast cancers from 92 patients. These laboratory
      findings were correlated with established clinical prognostic factors for each
      patient at the time of diagnosis, using a stepwise multiple analysis of variance
      (MANOVA). The stepwise MANOVA successively splits a group of patients into two
      mutually exclusive dissimilar groups, selecting the clinical prognostic factor
      that is most effective in doing so. Using this criterion, formation of the first
      three groups that were judged most dissimilar on the cytometry parameters was
      based on the number of positive nodes at the time of diagnosis. We show that
      ploidy, HER-2/neu protein content, and ras protein content, as measured by
      multiple parameter flow cytometry, are correlated with nodal status and other
      known clinical prognostic factors. The cell-by-cell multiparameter data suggest
      that for some individual tumors there are multiple genetic evolutionary pathways.
      Multiple genetic evolutionary pathways are also suggested by the MANOVA analysis.
      Focusing on the identification and analysis of genetic evolutionary pathways
      within individual tumors and across patients appears to offer a promising
      approach for defining the prognosis of early cancers.

PMID- 8529468
TI  - DNA ploidy and proliferation heterogeneity in human prostate cancers.
AB  - DNA ploidy determinations have been shown to have clinical application in
      predicting disease progression, survival, or response to anti-androgen therapies
      in prostate carcinomas. Since intra-tumor heterogeneity may have a profound
      effect on DNA measurements, we determined the frequency of DNA ploidy and
      proliferation (here S-phase fraction) heterogeneity in early prostatic
      carcinomas, and estimated the potential impact of heterogeneity on predicting
      disease course, survival, or response to therapy. Using image and flow cytometric
      analysis of archival, paraffin-embedded prostate tumors, we measured DNA ploidy
      in individual foci of prostatic carcinoma in stage T1a, T1b and T1c disease.
      Image analysis studies included the use of Feulgen stained tissue sections, and a
      comparison of these results with flow cytometric DNA ploidy determinations on
      nuclei isolated from the same tumor foci. Flow cytometry was also used to measure
      DNA Index and tumor S-phase fraction, in some cases using multiparameter analysis
      of isolated nuclei to determine DNA content and the level of the proliferation
      associated antigen, p105. Our results indicate that DNA aneuploid foci of
      prostate carcinoma are infrequently seen in stage T1a disease (13% of the
      individuals studied), and that the presence of both DNA diploid and aneuploid
      foci in the same sample is seen in less than 10% of these individuals. Stage T1b
      and T1c tumors containing only DNA diploid nuclei are seen, though these are
      likely most common in low volume, low Gleason grade tumors. By using flow
      cytometry to compare these results with those using image analysis of the same
      tumor foci, we demonstrated that the majority (> 75%) of these aneuploid tumors
      are DNA tetraploid. Our data on prostate tumor S-phase fractions indicate that
      DNA diploid tumors generally have a lower S-phase than DNA aneuploid foci
      (including comparisons of DNA diploid and aneuploid foci in the same prostate
      tumor). These results support the model that early prostate tumors are DNA
      diploid and have a low S-phase, and that these tumors likely evolve to DNA
      tetraploid tumors with a similar low S-phase fraction.

PMID- 8529469
TI  - Heterogeneity of chromosome 17 and erbB-2 gene copy number in primary and
      metastatic bladder cancer.
AB  - To study the relationship of tumor genomic heterogeneity with bladder cancer
      phenotype and p53 gene alterations, 138 primary bladder tumors were examined by
      dual labeling fluorescence in situ hybridization (FISH) using probes for
      chromosome 17 centromere (p17H8) and p53 (17p13.1). The number of different
      aneusomic populations > 5% (and monosomic populations > 20%) of cells served as a
      marker for heterogeneity. Nuclear p53 overexpression and Ki67 labeling index
      (Ki67 LI) were determined by immunohistochemistry. The number of aneusomic
      populations was 0 in 53 tumors, 1 in 18, 2 in 47, 3 in 9, and > 3 in 11 tumors.
      Presence of aneusomy was associated with tumor grade and stage (P < 0.0001 each).
      Ki67 LI was low in disomic tumors (11.0 +/- 7.7), higher in tumors with 1-3
      aneusomic populations (17.4 +/- 11.3), and highest in tumors with > 3 aneusomic
      populations (25.8 +/- 10.9; P = 0.02 for > 3 vs. 1-3 populations). Aneusomy and
      heterogeneity were associated with p53 alterations. Aneusomy was seen in 35% of
      tumors with neither p53 expression nor p53 deletion but in 97% of tumors with
      both p53 deletion and expression. Nine of 11 tumors with > 3 aneusomic
      populations exhibited both p53 deletion and overexpression. To study genomic
      heterogeneity in tumor progression, two recurrences and three metastases of a
      tumor with known erbB-2 amplification were examined for centromere 17 and erbB-2
      copy number. A considerable heterogeneity in centromere 17 and erbB-2 gene copy
      number was found in both recurrences and metastases, indicating a marked genomic
      instability in these metastatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529470
TI  - Heterogeneity of the proliferative fraction and cyclin D1/CCND1 gene
      amplification in head and neck squamous cell carcinoma.
AB  - High proliferative fraction and cyclin D1/CCND1 gene amplification have been
      associated with certain aggressive features of head and neck squamous carcinoma
      in some studies, but not in others. The differences may be related to the
      intratumoral heterogeneity of these factors. Moreover, the interrelationship
      between these seemingly related factors has not been determined. In order to
      determine the correlation between tumor proliferative fractions and CCND1 gene
      amplification, 3 spatially different samples from each of 32 primary head and
      neck squamous cell carcinomas (HNSCC) were separately analyzed by flow cytometry.
      A mixture of these specimens was also minced and snap frozen for molecular
      studies. DNA was extracted from patient lymphocytes, normal appearing squamous
      epithelium, and tumors. A genomic DNA probe containing the first exon of CCND1
      was used for hybridization by Southern technique. A 5.6 kb genomic DNA probe of
      immunoglobulin heavy chain was used as an internal standard for quantification of
      CCND1 gene amplification. Our results showed that 30% of the tumor cases
      manifested intratumoral heterogeneity (> 50% differences) of their proliferative
      activity. The highest value was used for correlation with gene amplification.
      Eleven (34.4%) of the 32 tumors showed CCND1 amplification (2-10-fold). When the
      proliferative fraction was dichotomized into high and low groups based on the
      mean value (> or = 13%), a highly statistical correlation between CCND1
      amplification and tumor proliferation was obtained (P < 0.001). No significant
      correlation between gene amplification and other clinicopathologic parameters was
      noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529471
TI  - Heterogeneous cell kinetics in tumors analyzed with a simulation model for
      bromodeoxyuridine single and multiple labeling.
AB  - Bromodeoxyuridine (BrdUrd) labeling of DNA and flow cytometry measurement of
      bivariate BrdUrd-DNA content distributions yield proportions of cells in the
      cycle phases. After application of BrdUrd, with time, these proportions change
      according to the cell kinetic parameters of the investigated cell line or tumor.
      In a previous study of S-phase transit time using the relative movement method,
      we obtained better fits with S-duration distributions rather than constant values
      (Baisch and Otto: Cell Prolif 26:439-448, 1993). Now, we have developed a
      simulation model using asymmetric phase duration distributions in all phases of
      the cell cycle to fit the experimental data after single or multiple BrdUrd
      labeling. The model includes transit of cells from proliferating to quiescent
      compartments in all phases. The results yield the phase duration distributions,
      mean and median percentages of quiescent cells in all phases, growth fraction,
      and potential doubling time. The model was used to fit data of five renal cell
      carcinomas xenotransplanted into nude mice that were obtained after single and
      multiple labeling up to 93 hours. The estimated phase duration distributions
      varied from narrow to extremely asymmetric. In particular, TG2M duration and
      asymmetry were nearly as large as those of G1 phase in some tumors. The
      contribution of inter- and intratumoral heterogeneity cannot be separated by the
      simulation model, but evidence of intratumoral heterogeneity is provided by DNA
      content distributions at extended time spans after BrdUrd labeling.

PMID- 8529472
TI  - Preferred genetic evolutionary sequences in human breast cancer: a case study.
AB  - Multiparameter flow cytometry studies were performed on the cells of an
      aggressive human breast cancer at the time of diagnosis and at relapse. The
      aneuploid cells that overexpressed large amounts of both HER-2/neu and ras
      survived intensive chemotherapy and were responsible for tumor relapse. At
      relapse, these cells were shown to overexpress simultaneously at least five
      oncogenes: HER-2/neu, ras, EGF receptor, p53 and c-myc. A partial reconstruction
      of the genetic evolutionary sequence in this tumor indicated that HER-2/neu
      overexpression was an early step in the sequence. Subsequent HER-2/neu
      overexpression, EGF receptor overexpression and p53 protein overexpression were
      each associated with ras overexpression. The data suggest that ploidy and
      oncogene overexpression cannot be used as independent clinical prognostic
      factors. The ability to characterize tumors according to the degree of
      advancement in the genetic evolutionary might serve as a basis for genetic
      staging for adjuvant therapy.

PMID- 8529473
TI  - Heterogeneity of bromodeoxyuridine sensitivity of cultured cells from melanoma
      metastases.
AB  - Continuously growing cell cultures, testing positive for tyrosine activity, were
      derived from two brain and three lymph-node metastases of five patients with
      malignant melanoma. These cell cultures were analyzed regarding their
      proliferation rate with continuous bromodeoxyuridine (BrdUrd) labeling followed
      by bivariate Hoechst 33258/ethidium bromide flow cytometry. Melanoma cell
      cultures are more sensitive toward BrdUrd in comparison to human diploid
      fibroblast cultures: 50% growth inhibition at 360 +/- 130 microM BrdUrd (range:
      130-520; n = 11) vs. 650 +/- 50 microM BrdUrd (n = 3) for fibroblasts. Moreover,
      BrdUrd sensitivity in melanoma cells is oxygen dependent: 50% growth inhibition
      at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs. 360 +/- 130 microM
      BrdUrd for 5% oxygen. The cell cycle kinetic mechanisms of BrdUrd-induced growth
      inhibition is accumulation of cells in the G2 phase. Cultures from a single
      metastasis showed up to a 3-fold variation in BrdUrd sensitivity. In one of the
      brain metastases two populations of different ploidy level (pseudotriploid vs.
      pseudotetraploid) and BrdUrd sensitivity could be resolved. Thus, continuous
      BrdUrd labeling followed by bivariate Hoechst 33258/ethidium bromide flow
      cytometry is a powerful tool to detect heterogeneity in proliferative capacity
      and drug sensitivity of cell populations within one tumor biopsy.

PMID- 8529474
TI  - Flow cytometric determination of glutathione in clinical samples.
AB  - Glutathione-based processes are believed to be important determinants of
      resistance to cancer chemotherapy, and measurement of glutathione (GSH) in tumor
      tissue is therefore of clinical relevance. Flow cytometric methods have been
      developed for measuring cellular GSH content that appear to correlate well with
      biochemical determinations. These flow cytometric techniques are rapid, allow
      tumor cells to be distinguished from stromal elements, and show considerable
      intratumoral heterogeneity in human tumor cell GSH content. Although large
      prospective studies are required to determine the correlations between GSH
      content and treatment outcome in cancer patients, this approach is a powerful
      alternative to standard biochemical assays for GSH.

PMID- 8529475
TI  - Heterogeneity of anthracycline retention and response to efflux blockers in human
      tumors.
AB  - Rapid cellular efflux of certain natural products used in cancer chemotherapy
      leads to reduced cytotoxicity and resistance. Multiple Drug Resistance (MDR) gene
      related glycoproteins are believed to act as the drug efflux pump. Several non
      cancer therapy drugs (e.g., verapamil, phenothiazines) compete for the p
      glycoprotein pump and thus can block efflux of a chemotherapeutic agent and
      overcome cellular resistance. Anthracyclines, such as adriamycin, are
      intrinsically fluorescent and thus their cellular retention can be determined by
      laser flow cytometry. This method has been used to study heterogeneity in
      cellular retention of anthracyclines and response to efflux blockers in human
      tumor cells. These studies have led to generation of clinical protocols where
      laser flow cytometry is used to monitor and overcome heterogeneity in drug
      retention of tumor cells from patients treated with a combination of adriamycin
      and efflux blockers.

PMID- 8529477
TI  - Cytogenetic heterogeneity and histologic tumor growth patterns in prostatic
      cancer.
AB  - Twenty-five prostatic adenocarcinomas were studied for the presence of
      intratumoral cytogenetic heterogeneity by interphase in situ hybridization (ISH)
      to routinely processed tissue sections. ISH with a chromosome Y-specific
      repetitive DNA probe provided a model to investigate patterns of chromosomal
      heterogeneity within and between different pathological grades. The Gleason
      grading system was used, since it is based on a detailed classification of growth
      patterns. Heterogeneity with respect to ploidy of the tumor was examined by ISH
      with a repetitive DNA probe specific for chromosome 1. The ploidy status of these
      cancers was confirmed by DNA flow cytometry (P < 0.001). Cytogenetic
      heterogeneity at the (Y) chromosomal level was observed between Gleason areas,
      within one area, and even within single tumor glands. The different patterns of
      chromosomal heterogeneity were seen in all tumor grades and stages. Differences
      in ploidy status were also found following the aforementioned histological
      patterns, again, in all grades and stages. Intraglandular heterogeneity was most
      frequently seen. No correlation was found between cytogenetic heterogeneity and
      proliferative activity (Ki-67 immunostaining). In contrast to current views on
      clonality, suggesting regional separation of subclones with different DNA
      content, this study demonstrates that these subclones can be interspersed.

PMID- 8529476
TI  - Use of a multiparametric panel to target subpopulations in a heterogeneous solid
      tumor model for improved analytical accuracy.
AB  - The exclusion of non-tumor and dead cells from the analysis of live tumor cells
      can significantly improve the accuracy of prognostic indicators such as
      proliferative and DNA indexes. To target live breast tumor cells in a
      heterogeneous breast tumor model, we have designed a panel consisting of the DNA
      specific dye DAPI and epithelial tissue-specific (cytokeratin), tumor-associated
      (MC5), proliferation-associated (proliferating cell nuclear antigen), and
      viability-associated (tubulin) markers. The breast tumor model consisted of a
      mixture of equal numbers of live and dead MDA-MB-175-VII (breast tumor) cells,
      live CEM (leukemic) cells, and live peripheral blood mononuclear cells. Targeting
      the live MDA cells in the mixture by gating on tubulin, cytokeratin, and MC5
      resulted in a sevenfold increase in PCNA positivity (from 3% ungated to 22.3%), a
      60% decrease in the %S-phase fraction (from 37.2% ungated to 15%), and
      elimination of extraneous hypodiploid and diploid components, enriching the
      tetraploid MDAs. These results are consistent with those obtained from unmixed
      live MDA cells. The combined utilization of this panel and "cumulative"
      electronic gating of the targeted population increases the number of relevant
      parameters that can be analyzed per sample and the accuracy of the resultant
      data.

PMID- 8529478
TI  - Detection of chromosome aneuploidy in breast lesions with fluorescence in situ
      hybridization: comparison of whole nuclei to thin tissue sections and correlation
      with flow cytometric DNA analysis.
AB  - We compared flow-cytometric DNA histogram pattern to counts of 4 fluorescent
      labelled centromeric probes (chromosomes 1, 7, 8, and 17) in whole nuclei (WN)
      and in nuclei from the corresponding formalin-fixed deparaffinized thin tissue
      section (TS) in 25 breast lesions (9 invasive carcinomas, 1 duct carcinoma-in
      situ, 5 fibroadenomas, 10 fibrocystic change). In benign lesions, signal gains
      (i.e., trisomic nuclei) were never observed in greater than 10% of nuclei from
      either WN or TS preparations. Loss of signal in benign breast lesions, however,
      varied considerably (0-43%) between individual case and between chromosome
      probes. The mean incidence of signal loss in WN of benign lesions ranged from
      8.9% (chromosome 7) to 14.4% (chromosome 1) of nuclei. These signal loss
      frequencies exceeded those of benign lymphoid control cells. In three benign
      lesions, signal loss in WN (with one probe) was observed in at least 25% of
      nuclei. Signal losses in benign TS, on average, were 50-150% greater than in
      matched WN preparations (chromosome 1-21.7%, chromosome 7-21.5%). Malignant
      lesions generally, but not always, displayed fewer monosomic nuclei and more
      trisomic nuclei in WN compared to TS, compatible with a slicing (i.e., nuclear
      truncation) artifact. Signal counts in carcinomas correlated well with flow
      cytometric DNA index; however, they were also characterized by evidence of
      genetic instability, manifest as signal gains in a subset of nuclei (10-25%) with
      individual probes in diploid range cases, as well as intratumoral heterogeneity,
      reflected as discrepancies in probe counts between WN and TS samples. We conclude
      that signal losses with centromeric probes are largely, but not entirely,
      explained by nuclear slicing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529479
TI  - Validation and rapid extraction of nucleic acids from alcohol-preserved ticks.

PMID- 8529481
TI  - Metformin and intestinal glucose handling.

PMID- 8529480
TI  - Effect of metformin on liver insulin metabolism and regional blood flow.

PMID- 8529482
TI  - Metformin-insulin interactions: from organ to cell.

PMID- 8529483
TI  - Metformin and free fatty acid metabolism.

PMID- 8529484
TI  - The effects of metformin on cardiovascular risk factors.

PMID- 8529485
TI  - Mechanisms of metformin action in non-insulin-dependent diabetes mellitus.

PMID- 8529486
TI  - Worldwide experience of metformin as an effective glucose-lowering agent: a meta
      analysis.

PMID- 8529487
TI  - The insulin-sparing effect of metformin in insulin-treated diabetic patients.

PMID- 8529488
TI  - Effects of metformin in obese patients with impaired glucose tolerance.

PMID- 8529489
TI  - Clinical perspectives on type 2 diabetes in North America.

PMID- 8529490
TI  - Socioeconomic consequences of non-insulin-dependent diabetes mellitus.

PMID- 8529491
TI  - Effect of metformin on various aspects of glucose, insulin and lipid metabolism
      in patients with non-insulin-dependent diabetes mellitus with varying degrees of
      hyperglycemia.

PMID- 8529492
TI  - Quality assessment and improvement in diabetes health care--an issue now and for
      the future.

PMID- 8529493
TI  - Natural course of diabetic peripheral neuropathy in spontaneous-onset diabetic
      Chinese hamsters.
AB  - We investigated metabolic and pathological changes in the peripheral nerve of the
      spontaneous-onset diabetic Chinese hamster. Electrophysiological examination
      revealed that the motor nerve conduction velocity was significantly decreased at
      10 months and afterwards, however, the F-wave latency was significantly increased
      at 5 months and afterwards. Concerning sciatic nerve contents of sorbitol, myo-
      and scyllo-inositol, the content of sorbitol was not significantly increased at 5
      months, but, myo- and scyllo-inositol were significantly decreased at 5 months
      and thereafter. At 10 and 15 months, however, sciatic nerve content of sorbitol
      was significantly increased. On morphological examination, loss of large
      myelinated fiber and reciprocal increase in degenerative fiber were also seen in
      sciatic nerve, but not in tibial nerve, at 5 months. At 15 months, these
      morphological changes were also found in the tibial as well as the sciatic nerve.
      Thus, we may hypothesize that F-wave latency is useful in the detection of
      initial diabetic neuropathy, and that the initial pathological changes in
      diabetic neuropathy of diabetic Chinese hamsters are predominantly found in the
      proximal site of peripheral nerves.

PMID- 8529494
TI  - A novel function of islet-derived CD8+T cells in initiating and developing
      autoimmune insulin-dependent diabetes mellitus in non-obese diabetic (NOD) mice.
AB  - Accumulated studies revealed that CD4+T cells were initially required for
      diabetes in NOD mice, whereas interaction of CD4+T/CD8+T cells is not fully
      understood. To address this question, we established islet-derived CD4+T cells
      and CD8+T cells from NOD mice. One NOD neonate that received CD4+T cells
      developed diabetes and insulitis with CD8+T cells. Administration of
      cyclophosphamide to non-diabetic recipients accelerated the development of
      diabetes, while none of the mice with anti-CD8 antibody did so. Similarly, it was
      observed that neonates that received islet-derived CD8+T cells developed diabetes
      and obvious insulitis mainly with CD4+T cells. Administration of anti-CD4
      antibody with transfer of CD8+T cells inhibited insulitis. These results imply
      that CD8+T cells function as an initial element to recruit CD4+T cells to islets
      as well as a final effector.

PMID- 8529495
TI  - Safety, efficacy, acceptability of a pre-filled insulin pen in diabetic patients
      over 60 years old.
AB  - The aim of the study was to evaluate safety, efficacy and acceptability of a pre
      filled insulin pen device (NovoLet) in diabetic patients over 60 years old
      already treated with insulin administered with conventional syringes. After a run
      in period of 2 weeks, 60 patients participated in a randomized cross-over study
      with two 6-week treatment periods using the insulin pen or conventional syringes.
      Insulin regimens did not change during the study. Hypoglycaemic episodes did not
      differ significantly between both kinds of treatment and no severe hypoglycaemia
      was registered. HbAlc (%) was (mean +/- S.D.) 7.7 +/- 1.2 and 7.9 +/- 1.1 during
      pen and syringe treatment, respectively. Blood glucose profiles were similar
      during both treatment modalities except for pre-lunch blood glucose values
      (mmol/l) lower during pen treatment (8.7 +/- 2.9 vs. 9.2 +/- 2.7, P < 0.01). The
      insulin dose (U/day) was 31.9 +/- 8.9 (pen) and 32.3 +/- 9 (syringe). 54 patients
      found the functioning of the insulin pen easy to understand and preferred it for
      future treatment because the conditions of insulin administration are faster and
      easier than with conventional syringes. We concluded that the pre-filled insulin
      pen is safe, efficacious and is highly accepted in over 60 years old diabetic
      patients.

PMID- 8529496
TI  - Effects of chromium supplementation on fasting insulin levels and lipid
      parameters in healthy, non-obese young subjects.
AB  - Trivalent chromium is an essential trace element for normal carbohydrate
      metabolism and insulin sensitivity. Because of this biological activity, chromium
      supplementation has been studied as a potential therapy of insulin resistant
      states and dyslipidemias, and has been promoted as a health aid to the general
      population. To determine if there is a risk of subclinical chromium deficiency in
      young, otherwise healthy adults, we evaluated the effect of chromium
      supplementation, versus placebo, on insulin levels and serum lipids in a double
      blind, randomized trial in 26 young adults (mean age 36 years). Fasting levels of
      glucose, immunoreactive insulin (IRI), and lipids (total cholesterol, HDL
      cholesterol, LDL cholesterol, triglycerides) were measured before and after 90
      days of daily supplementation with a chromium (III)-nicotinate preparation,
      containing 220 micrograms elemental chromium, or placebo. There were no
      statistically significant differences in the percentage change of fasting
      glucose, IRI or lipids between the chromium (n = 15) and placebo (n = 11) groups
      after 90 days of supplementation. However, those individuals within the chromium
      group with initial fasting IRI levels greater than 35 pmol/l had a significant
      decrease in IRI level after supplementation (P < 0.03) despite no significant
      changes in serum lipids. These subjects may benefit from chromium supplementation
      by improving insulin sensitivity and cardiovascular risk over time.

PMID- 8529497
TI  - Glycemic control, growth and complications in children with insulin-dependent
      diabetes mellitus--a study of children enrolled in a Summer camp program for
      diabetics in Kinki district, Japan.
AB  - The influence of glycemic control on growth and on the development of
      complications in diabetic children was studied. The subjects of the study were
      107 children with insulin-dependent diabetes mellitus (IDDM), who were enrolled
      in a Summer camp program for diabetic children in Kinki District, Japan from 1972
      to 1990, and who had at least three determinations of HbA1 during the observation
      period. Many of the children had high mean levels of HbA1, regardless of age. The
      height and weight were below the standards for the respective ages in many
      children, indicating the retardation of growth. However, S.D. scores for height
      and weight and other physical indices were not related to the mean levels of
      HbA1. By contrast, the prevalence of diabetic retinopathy was related to an
      elevated mean level of HbA1, but that of albuminuria was not. Serum cholesterol
      levels were higher in children with higher mean levels of HbA1, but serum
      triglycerides appeared not to be related to glycemic control. The incidence of
      retinopathy during the observation period closely related to the degree of the
      mean levels of HbA1, but that of albuminuria did not.

PMID- 8529498
TI  - Antibodies to GAD in Japanese diabetic patients: a multicenter study.
AB  - We determined the prevalence of antibodies to glutamic acid decarboxylase (anti
      GAD) in Japanese diabetic patients. Anti-GAD were detected by RIP Anti-GAD
      Hoechst, which is a new sensitive radioimmunoassay (RIA) kit using purified pig
      brain GAD as the antigen. One thousand nine hundred Japanese patients were
      collected by the Study Group for Antibodies to GAD. The prevalence of anti-GAD in
      the subjects of this study was: 35.4% (326/921) in all patients with IDDM, 50.3%
      (96/191) in patients with IDDM less than 1-year duration, 4.3% (29/680) in NIDDM,
      37.9% (39/103) in slowly progressive IDDM, 10.5% (4/38) in gestational diabetes
      mellitus, 0% (0/27) in impaired glucose tolerance, 4.8% (6/124) in the school
      children with glycosuria, 2.1% (1/47) in the relatives of IDDM and 5.0% (1/20) in
      neurological diseases without diabetes. The prevalence in normal subjects was
      2.2% (7/323). Anti-GAD are frequently detected by the RIA kit in patients with
      IDDM of short duration and this assay may be useful for population screening for
      IDDM and for better understanding of its pathogenesis.

PMID- 8529499
TI  - The effects of calcium channel blockers, verapamil, nifedipine and diltiazem, on
      metabolic control in diabetic rats.
AB  - The effects of calcium channel blockers (CCB)-verapamil, nifedipine, diltiazem on
      metabolic control in streptozotocin-induced long-term diabetes in rats were
      investigated. Diabetes mellitus was induced by single intravenous injection of
      streptozotocin (65 mg/kg body wt.). The animals were divided into five groups: a
      healthy control group, a diabetic group and three diabetic groups treated with
      one of the calcium channel blockers (verapamil, 25 mg/kg/day, nifedipine, 20
      mg/kg/day, and diltiazem, 30 mg/kg/day, respectively). Body weight, glycemia,
      glycated hemoglobin and total serum protein levels of these animals were measured
      at the beginning and at the end (after 13 weeks) of the experiment. It was
      observed that diabetic animals who were not treated with CCB had lost weight at
      the end of the experiment (P < 0.01). The blood glucose and glycated hemoglobin
      levels were increased in the diabetic group in comparison to the healthy control
      group (P < 0.001). However, the calcium channel blockers seem to have beneficial
      effects on body weight, glycated hemoglobin and blood glucose levels.

PMID- 8529500
TI  - A patient with diabetes mellitus, cardiomyopathy, and a mitochondrial gene
      mutation: confirmation of a gene mutation in cardiac muscle.
AB  - A 44-year-old woman with diabetes mellitus, cardiomyopathy, and a mitochondrial
      gene mutation, was reported. She was diagnosed as having diabetes at 33 years of
      age and was treated with insulin. However, she stopped treatment 6 months later
      and had no medical care until she developed diabetic ketoacidosis at 41 years of
      age. She had diabetic foot, diabetic retinopathy, and nephropathy with low
      insulin secretory capacity, leading to insulin treatment. A point mutation of the
      mitochondrial tRNA(Leu(UUR)) gene was identified in peripheral leukocytes at 43
      years of age, and sensorineural hearing impairment was detected at the same time.
      Her mother also suffered from diabetes mellitus with deafness and her son, who
      was not diabetic at age 19, had the same mitochondrial DNA (mtDNA) mutation. At
      44 years of age, she developed congestive heart failure due to cardiomyopathy,
      and the same mtDNA mutation was identified in the cardiac muscle. Thus, it is
      very likely that in this patient, diabetes and cardiomyopathy was caused by the
      same abnormality, the point mutation of mitochondrial tRNA(Leu(UUR)) gene.

PMID- 8529501
TI  - New Oral Antidiabetic Agents: From Today and Tomorrow. Proceedings of the Hoechst
      Satellite Symposium to the 15th International Diabetes Federation Congress. Kobe,
      Japan, 4-5 November 1994.

PMID- 8529502
TI  - Extrapancreatic effects of sulfonylurea drugs.
AB  - Extrapancreatic action of sulfonylurea (SU) drugs were extensively summarized.
      Hypoglycemic SU drugs stimulate glycolytic pathway and inhibit gluconeogenic
      pathway in the liver through regulating key enzymes such as the bifunctional
      enzyme PFK2/F-2,6-P2ase and PEPCK. It is possible that SUs improve the primary
      defects in NIDDM through both pancreatic and extrapancreatic actions.

PMID- 8529503
TI  - Influence of oral sulfonylurea agents on hepatic glucose uptake.
AB  - Although the metabolic derangement in the subjects with well-established NIDDM is
      characterized by both insulin resistance and diminished insulin secretion, the
      impaired sensitivity to insulin in the target tissues is assumed to represent the
      primary defect in most NIDDM individuals. Therefore, the therapeutic modality
      that can augment insulin-mediated glucose metabolism in the target tissues seems
      rational in the treatment of NIDDM. Glimepiride (HOE490), a newly developed
      sulfonylurea, has been reported to have a more potent hypoglycemic action than
      glibenclamide while its ability to stimulate insulin secretion is much weaker.
      Thus, part of the potent hypoglycemic action of HOE490 has been speculated as
      being due to an extrapancreatic effect. First we examined the effect of strict
      glycemic control on insulin resistance seen in NIDDM using euglycemic
      hyperinsulinemic clamp combined with oral glucose loading (Clamp-OGL) to 9
      subjects with NIDDM. After 3 to 4 weeks of intensified insulin therapy, insulin
      mediated glucose uptake by the liver significantly increased while peripheral
      glucose disposal did not change. Secondly we applied Clamp-OGL to 5 subjects with
      IDDM to study the acute metabolic effect of HOE490 on glucose handlings by the
      target tissues. Intravenous administration of HOE490 at a rate of 6.0
      micrograms/min did not affect hepatic glucose uptake in these subjects. Thus we
      studied subacute metabolic effect of HOE490 on glucose handlings by the target
      tissues in 7 normal dogs using euglycemic clamp combined with hepatic venous
      catheterization technique.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529504
TI  - Extrapancreatic effects of sulfonylureas--a comparison between glimepiride and
      conventional sulfonylureas.
AB  - The contribution of extrapancreatic effects of sulfonylureas to the blood glucose
      decreasing activity was reevaluated in vivo and in vitro with several
      conventional sulfonylureas and with the new one glimepiride. In vivo, in dogs,
      after single approximately equipotent blood glucose-decreasing doses, the
      sulfonylureas were tested for a ranking in the ratios of mean plasma insulin
      increasing and blood glucose-decreasing activity. Studies were also performed in
      hyperglycemic hyperinsulinemic KK-Ay mice under once daily treatment for 8 weeks.
      In vitro, glimepiride and glibenclamide were tested for the ranking of their
      extrapancreatic activity with respect to the stimulation of glucose transport and
      glucose metabolizing processes in normal and insulin-resistant fat cells as well
      as in the isolated diaphragm. Furthermore, in vitro studies were performed,
      especially with glimepiride, in order to characterize the molecular mechanism for
      the extrapancreatic activity. The dog studies revealed a marked ranking in the
      ratios of plasma insulin-increasing and blood glucose-decreasing activity between
      the different sulfonylureas (glimepiride < glipizide < gliclazide <
      glibenclamide). In the hyperglycemic hyperinsulinemic KK-Ay mice, glimepiride
      reduced blood glucose by 40%, plasma insulin by 50% and HBA1c by 33%, whereas
      glibenclamide and gliclazide had no effect on these parameters. In vitro,
      glimepiride and glibenclamide had extrapancreatic effects within the lower microM
      range, with glimepiride exhibiting 2-3-fold lower ED50 values than glibenclamide.
      In the absence of insulin, both stimulated glucose transport--up to 60% of the
      maximum insulin response in the rat diaphragm and up to 35% in 3T3 adipocytes.
      Glycogenesis was stimulated in the rat diaphragm--up to 55% of the maximum
      insulin effect; lipogenesis in 3T3 adipocytes--up to 40%. The studies on the
      molecular mechanism of extrapancreatic activity with rat adipocytes and diaphragm
      suggest that these direct insulin-mimetic effects rely on the induction of GLUT4
      translocation from internal stores to the plasma membrane and on the activation
      of the key metabolic enzymes, glycogen synthase and glycerol-3-phosphate
      acyltransferase. These processes occur within the same drug concentration range
      and with the same ranking between glimepiride and glibenclamide as observed for
      glucose utilization and transport. The direct effects of sulfonylureas may
      ultimately be regulated by a glycosyl-phosphatidylinositol-specific phospholipase
      C, shown to be activated by glimepiride in rat adipocytes. Lipolytic cleavage
      products thereby generated from glycolipidic structures may in turn stimulate
      specific protein phosphatases which activate key regulatory proteins/enzymes of
      glucose and lipid metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8529505
TI  - Pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM).
AB  - In this review, the pathophysiologycal events leading to hyperglycemia in NIDDM
      patients are discussed, i.e. glucose effectiveness, insulin action (in muscle and
      liver) and insulin secretion. The natural history of the insulin resistance
      syndrome is demonstrated and a new staging system is proposed. We conclude that
      NIDDM is a life-long disease characterized by intraabdominal obesity and
      macrovascular events several years in advance of hyperglycemia, and that insulin
      resistance in skeletal muscle plays an important pathophysiological part and also
      may be used in prediction of the disease.

PMID- 8529506
TI  - Clinical profile of glimepiride.
AB  - In order to achieve appropriate blood glucose control, the treatment of non
      insulin dependent (NIDDM) Type II diabetes usually starts with diet and exercise.
      If this still results in insufficient metabolic control, oral hypoglycaemic drugs
      or insulin are added to the non-pharmacological measures. Sulphonylureas have
      been used successfully as oral hypoglycaemic agents since the 1950s but there are
      aspects where medication could be better adjusted to the patients' needs.
      Preclinical investigations on animals and in vitro studies with glimepiride
      (HOE490), a new sulphonylurea, suggested some benefit over sulphonylureas
      currently available, including lower dosage, rapid onset and long duration of
      action, lower insulin and C-peptide levels, possibly due to less stimulation of
      insulin secretion and more pronounced extrapancreatic effects. The clinical
      relevance of these findings were studied in clinical trials. 19 phase II and 4
      phase III clinical studies, in a total of about 3750 Type II diabetic patients,
      established efficacy and safety of glimepiride in comparison to placebo and
      glibenclamide and showed its therapeutic value. 1 mg per day induced a marked
      blood glucose reduction (FPG 2.4 mmol/l; HbA1c 1.2%) which could be enhanced by
      increasing the dose to the maximum effective 4 and 8 mg daily. In patients,
      glimepiride had a more rapid onset of action than glibenclamide, with a long
      duration of action. Glimepiride achieved metabolic control with the lowest dose
      (1-8 mg daily) of all the sulphonylureas. In addition, it maintained a more
      physiological regulation of insulin secretion than glibenclamide during physical
      exercise, suggesting that there may be less risk of hypoglycaemia with
      glimepiride.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529507
TI  - Clinical evaluation of glimepiride (HOE490) in NIDDM, including a double blind
      comparative study versus gliclazide.
AB  - In order to investigate the clinical usefulness of glimepiride in NIDDM, some
      clinical trials were conducted. In a double-blind comparative study versus
      gliclazide, glimepiride was as efficacious as gliclazide. However, a subgroup
      analysis suggested glimepiride may have been more effective in severe patients
      treated by large doses of glibenclamide.

PMID- 8529508
TI  - Lessons from UK prospective diabetes study.
AB  - Type II diabetes is a major cause of morbidity and mortality, both from an
      increased risk of developing cardiovascular disease and from specific diabetic
      complications. At present, patients are often treated to prevent marked
      hyperglycaemia, that induces symptoms such as thirst. Moderately raised glucose
      levels are then accepted. At present, it is uncertain whether Type II diabetes
      should be treated more intensively, with diet, tablet or insulin therapy to
      maintain near-normal glucose levels, in order to prevent the onset of
      complications. The Diabetes Control and Complications Trial (DCCT) in insulin
      dependent diabetic subjects with a mean age of 27 years has indicated that
      intensive therapy to achieve a haemoglobin A1c level of 7.1%, compared with 9.0%
      in a 'standard control group', will retard the progress of diabetic microvascular
      disease. It is not known whether this is similarly beneficial in Type II diabetic
      subjects, where the main complication is cardiac disease, or whether the even
      better control that can be obtained with pharmaceutical therapy in Type II
      diabetic patients would be worthwhile. It is similarly not known whether
      treatment with sulphonylurea, metformin or insulin is particularly beneficial or
      whether any of these therapies is potentially harmful. The UK Prospective
      Diabetes Study (UKPDS) has randomly allocated 4209 newly diagnosed Type II
      diabetic patients to different therapies and is determining: (a) whether improved
      glucose control will delay the onset of clinical complications; and (b) whether
      any specific therapy has advantages or disadvantages.

PMID- 8529509
TI  - What therapy do our NIDDM patients need? Insulin releasers.
AB  - NIDDM is the result of concomitant defects in both insulin secretion and insulin
      action. Although plasma insulin concentration in NIDDM patients may be normal or
      even increased as compared to normal individuals, insulin secretion is always
      impaired when related to ambient hyperglycemia. Moreover, the loss of first-phase
      insulin secretion is always present and it occurs at the very early stage of the
      disease. The defect in the early release of insulin may have quite an impact in
      post-prandial glucose homeostasis, due to inadequate suppression of hepatic
      glucose production. Therefore, insulin releasers should be able; 1. to increase
      total insulin secretory capacity, and 2. to restore physiologic profile of
      insulin secretion. However, this is rarely achieved with the current
      therapeutical tools. Sulfonylureas may exert some suppressive action on the liver
      and may maintain a portal-peripheral venous insulin gradient. Metformin may
      improve insulin sensitivity but has no effect on the beta-cell. Exogenous insulin
      exerts an inhibitory effect on hepatic glucose production but it does not
      maintain the physiologic gradient, neither can it mimic first-phase insulin
      secretion. Therefore, more appropriate tools must be sought. Prompt stimulation
      of insulin secretion can be elicited by alpha 2-adrenoreceptor antagonists, but
      their clinical use is still under evaluation. New sulfonylureas are under
      development, though some of them may exert a better peripheral action than more
      potent stimulation of the beta-cell. Special interest has been focused on
      incretin peptides. Infusion of glucagon-like peptide 1 (GLP-1) in NIDDM patients
      improves glucose tolerance through enhancement of acute release of insulin,
      suppression of glucagon secretion, and improvement of peripheral glucose
      utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529510
TI  - Acarbose for the treatment of type II diabetes: the results of a Canadian multi
      centre trial.
AB  - The treatment of Type II diabetes (NIDDM) includes an appropriate diet and
      prudent exercise program. If these measures are insufficient to control the blood
      sugar, oral agents (sulphonylureas or biguanides) or insulin are added to the
      therapeutic regimen. Although the diet prescription has undergone some changes
      and refinements, this approach has been the traditional treatment for NIDDM for
      nearly 40 years. Recently a new class of oral agents, the alpha-glucosidase
      inhibitors, has become available. These drugs are competitive inhibitors of the
      alpha-glucosidase enzymes in the brush border of the bowel wall. They act to slow
      and delay the rate of carbohydrate absorption, thereby decreasing postprandial
      hyperglycemia. A recent study was designed to evaluate the long-term efficacy of
      acarbose, an alpha-glucosidase inhibitor, in improving the glycemic control of
      patients with NIDDM who were sub-optimally controlled on either diet alone, or
      diet plus sulphonylurea, metformin or insulin. A total of 354 patients with NIDDM
      were studied, 77 on diet alone, 83 on metformin, 103 and sulphonylurea and 91 on
      insulin. Subjects in each treatment stratum were randomized, double-blind to
      either acarbose or placebo, for 1 year. At baseline and every 3 months
      thereafter, fasting and postprandial glucose and C-peptide, HbA1c and fasting
      lipids were measured. Compared to placebo, acarbose treatment resulted in a
      decrease in mean postprandial glucose in all four strata (19 +/- 0.8 to 15.3 +/-
      0.7 mmol/l: P < 0.001). This effect was even more pronounced and highly
      statistically significantly different when comparing the postprandial plasma
      glucose incremental area under the curve between placebo and acarbose
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529511
TI  - Pathogenesis of insulin resistance: modulation of the insulin signal at receptor
      level.
AB  - The insulin resistance of skeletal muscle plays an important role in the
      pathogenesis of the metabolic endocrine syndrome and diabetes mellitus Type II.
      Impairment of the signal transmission from the insulin receptor to glycogen
      synthase and the glucose transport system was shown in insulin resistant
      subjects. A reduced receptor activation contributes also to insulin resistance.
      We investigated the mechanisms of modulation of receptor function in isolated
      cell systems which are transfected with human insulin receptor. Action of TNF
      alpha and acute hyperglycaemic effects were studied in particular. Acute
      hyperglycaemia gives rise, in the isolated cell system, to inhibition of the
      tyrosine kinase activity of the insulin receptor within a few minutes. This
      inhibitory effect seems to be mediated by translocation and activation of various
      isoforms of protein kinase C. Activation of protein kinase C probably leads to
      phosphorylation of the beta-subunit of the insulin receptor at serine residues.
      The domains of the insulin receptor, which are responsible for the inhibitory
      effect of hyperglycaemia do not seem to be localized either in the C terminus or
      in the juxtamembranary region of the insulin receptor. The hyperglycaemic effect
      can be antagonized in the isolated cell system both by protein kinase C
      inhibitors and so-called insulin sensitizers such as thiazolidindiones. Similar
      inhibitory effects, as induced by hyperglycaemia, can also be mediated by
      administration of the cytokine TNF alpha. As TNF alpha is probably increasingly
      expressed in obesity, the modulation of receptor kinase activity by TNF alpha
      could be an important factor for insulin resistance in obesity.

PMID- 8529512
TI  - Insulin therapy in type II diabetes.
AB  - When diet therapy is no longer effective in keeping the fasting plasma glucose
      level < 6 mmol l-1, a basal insulin supplement from a long-acting insulin such as
      ultralente can be added instead of using a sulphonylurea or metformin. The dose
      of insulin required can be predicted from the level of the fasting plasma glucose
      and the degree of obesity, which provides an index of the accompanying insulin
      resistance. The risk of hypoglycaemia is minimal provided that the dose is
      adjusted according to the fasting plasma glucose concentration and the patient
      can continue a normal life-style without restrictions concerning exercise or the
      size of individual meals. If given in appropriate doses a basal insulin
      supplement does not induce marked weight gain and insulin therapy is equally
      appropriate in patients with insulin deficiency and insulin resistance.
      Maintaining near-normal glucose concentrations probably outweights a putative
      risk of hyperinsulinaemia. In more severely affected patients, such as those with
      sulphonylurea failure, soluble insulin to cover meals in addition to a basal
      insulin supplement is needed. At this stage it is usual to stop tablet therapy
      and treat patients with either a basal and prandial insulin regimen or with twice
      daily soluble and isophane mixtures. Nevertheless, in elderly patients in whom
      regular meals cannot be guaranteed, continuing with sulphonylurea therapy and
      adding a basal insulin supplement can be a safe and effective way of preventing
      hyperglycaemic symptoms.

PMID- 8529513
TI  - Insulin-like growth factor I (rhIGF-I) as a therapeutic agent for
      hyperinsulinemic insulin-resistant diabetes mellitus.
AB  - Insulin resistance is one of the major underlying abnormalities in NIDDM,
      however, its pathophysiologic mechanisms are not well understood. Many clues
      about the mechanisms of insulin action have come from patients with the most
      severe forms of insulin resistance, including those with genetic abnormalities in
      the insulin signal transduction cascade. We used rhIGF-I as a probe to
      differentiate insulin and IGF-I action and to study the therapeutic potential of
      IGF in states of insulin resistance. To date, we have studied six subjects with
      varying phenotypes of severe insulin resistance but without mutations in the
      insulin receptor itself. All subjects underwent baseline physiologic monitoring
      to quantitate carbohydrate tolerance, insulin secretion, and insulin action prior
      to receiving rhIGF-I at 100 micrograms/kg body wt s.c. bid for 1 month with
      interval testing of glycemic control and insulin sensitivity. None of the six
      subjects noted significant side effects from the rhIGF-I. Four of the six
      subjects had overt diabetes during control testing; three of these subjects
      demonstrated normalization of fasting and postprandial blood glucose
      concentrations during rhIGF-I administration on no other therapy. In the fourth
      patient, insulin requirements and fasting hypertriglyceridemia decreased without
      improvement in glycemic control. The two subjects with normal glucose tolerance
      (two sisters with congenital lipodystrophy) maintained normal glucose tolerance
      at dramatically lower insulin levels and had a dramatic reduction in triglyceride
      levels. The efficacy of IGF-I continued to increase over the duration of the
      study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529514
TI  - Rationale and hurdles of inhibitors of hepatic gluconeogenesis in treatment of
      diabetes mellitus.
AB  - A typical clinical feature of patients with fasting hyperglycemia in diabetes is
      well correlated with accelerated hepatic glucose production which is determined
      by elevated FFA-induced gluconeogenesis. Therefore, to treat fasting
      hyperglycemia, inhibition of both FFA release and fatty acid oxidation in the
      liver may be efficient modalities of treatment. (1) Inhibitor of FFA release: a
      novel selective adenosine A1 agonist, SDZ WAG 994 is a potent inhibitor of
      adenosine deaminase-induced lipolysis. Twenty-three-week old, male GK rats
      showing glucose intolerance were treated with WAG 994 (1000 micrograms/kg body
      weight) for 16 days. Plasma glucose level at 0 time in WAG group was
      significantly (P < 0.01) less than that of the control. Both plasma FFA and
      triglyceride concentrations also decreased by 54% and 74%, respectively (vs.
      control GK rats). (2) Inhibition of hepatic fatty acid oxidation: beta
      aminobetaine (emeriamine) is a water-soluble carnitine analog and inhibition of
      CPT-1 in isolated hepatocytes is 100 times more sensitive than that in isolated
      cardiocytes and it suppresses both gluconeogenesis and ketogenesis by 60-80%.
      However, it may be possible that this drug may induce fat deposition in the
      liver. An inhibitor of elevated fatty acid release from adipose tissue in
      concomitant with liver-specific and reversible inhibition of fatty acid oxidation
      may be an effective agent with hypoglycemic and hypolipidemic action for the
      treatment of diabetes mellitus.

PMID- 8529515
TI  - Alternative therapeutic principles in the prevention of microvascular and
      neuropathic complications.
AB  - Since the prevention of chronic diabetic complications by near normal metabolic
      control is not always achievable, alternative therapeutic principles have been
      developed. The specific intervention at metabolic abnormalities which seem to
      play a key role in the pathogenesis of complications has been shown to prevent
      the development of microangiopathy and neuropathy in experimental diabetes, e.g.
      inhibition of non-enzymatic glycation by aminoguanidine, inhibition of polyol
      pathway activity by aldose reductase inhibitors, prevention of hypoxia and
      oxidative stress by vasodilators and radical scavengers such as alpha-lipoic
      acid. Some of these drugs should soon be available for common clinical use.

PMID- 8529516
TI  - Insulin secretion in obese and non-obese NIDDM.
AB  - Both the insulin response to glucose and the sensitivity to insulin show large
      variation in the normal population. Many subjects have either a markedly low
      insulin response or low sensitivity to insulin, with nevertheless normal glucose
      tolerance. For such subjects to become diabetic, insulin secretion or insulin
      action must further deteriorate with time, or other factors are added which tip
      the balance towards diabetes. Most evidence to date indicates that reduced beta
      cell responsiveness and reduced insulin sensitivity co-exist in subjects prior to
      developing NIDDM. Both insulin secretion and insulin action are genetically
      controlled and influenced by intrauterine and neonatal factors. Insulin secretion
      and insulin action vary inversely in a closely linked manner; inability to fully
      compensate for changes in one variable may generate a functional deficit in
      glucose homeostasis. Subjects combining low functions would run a proportionately
      larger risk of decompensating the glucose tolerance and be more vulnerable, in
      terms of diabetes susceptibility, to factors that further reduce insulin output
      or insulin action. Careful analysis of existing data prompts us to ascribe a
      dominating role to the impairment of insulin secretion in the pathogenesis of IGT
      and NIDDM. Patients with NIDDM also exhibit increased proportions of proinsulin
      and proinsulin conversion intermediates. We used hyperinsulinaemic diabetic and
      non-diabetic Psammomys obesus to study the possible relationship between steady
      state pancreatic insulin stores and the proportion of proinsulin-related peptides
      in the plasma and the pancreas. A marked increase in these peptides was
      associated with 90% reduction in insulin stores of the pancreas. After food
      deprivation, the depletion of pancreatic insulin in the diabetic animals was
      partially corrected, and the proinsulin/insulin ratio normalized. In contrast,
      non-diabetic psammomys showed only 50% reduction in pancreatic insulin stores
      under non-fasting conditions, with no change in proinsulin/insulin ratio. These
      findings suggest that in the diabetic Psammomys obesus, pancreatic capacity for
      storage/production of insulin is limited; the metabolic consequences of this
      limitation are amplified by increased secretory demand secondary to insulin
      resistance, thus facilitating the establishment of hyperglycaemia, which may in
      itself further exacerbate the pancreatic dysfunction.

PMID- 8529517
TI  - NIDDM--the devastating disease.
AB  - Of the various types of diabetes mellitus, non-insulin-dependent diabetes (NIDDM)
      is by far the most common and is increasing rapidly in many populations around
      the world. It is a heterogeneous disorder, characterized by a genetic
      predisposition and interaction between insulin resistance and decreased
      pancreatic beta-cell function. There is a strong association between the presence
      of obesity and low levels of physical exercise and the development of NIDDM.
      However, NIDDM may also develop in lean individuals and the incidence increases
      significantly with increasing age. A diagnosis of impaired glucose tolerance or
      gestational diabetes is a strong predictor for future development of NIDDM and
      should signal appropriate interventions to prevent or delay the progression to
      NIDDM. NIDDM is frequently associated with other conditions such as hypertension,
      hypertriglyceridemia and decreased high-density lipoprotein which are additional
      risk factors for atherosclerosis and cardiovascular disease. The 'insulin
      resistance syndrome', which includes obesity, NIDDM, hypertension,
      hyperinsulinemia and dyslipidemia is a major and increasing cause of morbidity
      and mortality in many populations. In addition, people with NIDDM and poor
      glycemic control may develop severe microvascular complications of diabetes,
      including retinopathy, nephropathy and neuropathy. Appropriate diet, weight
      control and increased physical activity will increase insulin sensitivity in
      insulin resistant patients and are effective treatments for patients with NIDDM
      or may prevent the development of NIDDM in susceptible individuals. If these
      measures are unsuccessful, then oral hypoglycemic agents or insulin therapy may
      be required.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529518
TI  - Pancreatic pathology in non-insulin dependent diabetes (NIDDM).
AB  - NIDDM is a heterogeneous disease and subgroups of NIDDM include MODY (Maturity
      Onset Diabetes of the Young), Malnutrition-related diabetes (MRDM) and
      Fibrocalculus pancreatic diabetes (FCPD). Endocrine cell population is relatively
      unchanged in NIDDM: B-cells are reduced by up to 30% and A-cells increased by
      10%. Islet amyloid is found in 96% of subjects occupying up to 80% of the islet
      associated with a reduction in B-cells. Amyloid formation is unlikely to cause
      diabetes but progressive accumulation increases the severity of the disease.
      Islet amyloid is formed from the islet amyloid polypeptide (IAPP), a normal
      constituent of B-cells, co-secreted with insulin. The causal factors for IAPP
      fibrillogenesis are unknown but abnormal synthesis or overproduction could be
      involved: stimulation of B-cell secretion in NIDDM by obesity, hyperglycaemia or
      suphonylurea therapy may promote amyloidosis and further aggravate islet
      pathology. A mutation of the glucokinase gene in MODY leads to diminished B-cell
      secretion but not amyloid formation. Diabetes and mutations of mitochondrial DNA
      is associated with poorly developed islet structure. Exocrine pancreatic size is
      reduced and there is evidence of sub-clinical chronic pancreatitis in NIDDM. In
      MRDM and FCPD, chronic pancreatitis and exocrine necrosis is associated with
      reduced insulin secretion. Unlike cystic fibrosis where islet amyloid is present
      in diabetic individuals, amyloid is absent from subjects with FCPD. Pathological
      changes in the exocrine and endocrine pancreas in NIDDM results from and
      contributes to the pathophysiology of insulin secretion in NIDDM.

PMID- 8529519
TI  - Targets of therapy for NIDDM.
AB  - Non-insulin-dependent diabetes (NIDDM) is a common multimetabolic disorder with
      potential (and potentially severe) long-term complications affecting large and
      small blood vessels. Where microvascular complications (retinopathy, nephropathy
      and neuropathy) are concerned, the Diabetes Control and Complications Trial
      (DCCT), as well as much circumstantial evidence, suggests that hyperglycaemia is
      the main aetiological factor and this is likely to apply in NIDDM as well as
      IDDM. Unfortunately, achieving normoglycaemia in NIDDM is not easy and it is
      unclear whether insulin has advantages over oral hypoglycaemic agents or vice
      versa. Turning to macrovascular disease, it is unclear which of the many
      potentially atherogenic abnormalities-hypertension, hyperinsulinaemia,
      hyperlipidaemia, etc-are most important. A further problem is that macrovascular
      disease is already well developed in many patients when NIDDM is diagnosed and we
      do not know whether secondary prevention is effective. Nevertheless, it is
      sensible to try to reverse the atherogenic milieu and this should be done in the
      first instance by lifestyle modification rather than drugs. Even if we cannot
      manipulate the biochemistry to prevent small or large vessel complications, much
      can still be done; proactive foot care can prevent ulceration, timely laser
      treatment can prevent visual loss and thrombolytic therapy is relatively more
      effective in diabetic patients with myocardial infarction than in their non
      diabetic peers. Finally, patients with NIDDM need intensive education and each
      needs an individualised treatment plan and goals.

PMID- 8529520
TI  - The role of potassium channels in excitable cells.
AB  - Potassium (K) channels regulate cellular excitability. Their opening
      hyperpolarises the membrane potential and induces quiescence whereas their
      closure produces depolarisation and excitation. One K-channel superfamily
      includes the delayed rectifier (KV), the A-type (KA) and the large conductance,
      Ca-sensitive (BKCa) channels. These serve to terminate excitatory events and
      consist of a tetramer of alpha-subunits each comprising six transmembrane
      spanning segments including a voltage-sensor. Additional beta-subunits which
      modify inactivation and voltage sensitivity may also be present. Channels in the
      second superfamily include the inward rectifiers (KIR) and the ATP-sensitive K
      channel (KATP). Their tetrameric assembly of alpha-subunits contains only two
      transmembrane-spanning segments and lacks a voltage sensor. KATP is associated
      with a sulphonylurea binding site belonging to the ATP-binding cassette family.
      Although KIR conducts poorly at potentials positive to EK, both it and KATP do
      conduct over the physiological potential range. K-channel modulators are
      important in determining channel function. These include drugs like
      tetraethylammonium and 4-aminopyridine and more recently-discovered selective
      agents active at KATP and BKCa. These are typified by diazoxide, levcromakalim
      and glibenclamide and by NS1619, iberiotoxin and penitrem A, respectively.

PMID- 8529521
TI  - The molecular interaction of sulfonylureas with beta-cell ATP-sensitive K(+)
      channels.
AB  - The molecular interaction of glimepiride and glibenclamide with the beta-cell
      sulfonylurea receptor was investigated by kinetic and steady state binding as
      well as photoaffinity labeling. The novel sulfonylurea, glimepiride, exhibits a
      significantly higher exchange rate with the sulfonylurea receptor but a 2.5-3
      fold lower binding affinity compared to glibenclamide. [3H]Glimepiride was
      specifically incorporated into a 65-kDa polypeptide under conditions which led to
      predominant labeling of a 140-kDa protein by [3H]glibenclamide. Labeling of the
      140-kDa protein by [3H]glibenclamide was inhibited by unlabeled glimepiride and,
      vice versa, glibenclamide inhibited labeling of the 65-kDa protein by
      [3H]glimepiride. The 65-kDa protein was also specifically photolabeled by the
      sulfonylurea [125I]35623, whereas an 4-azidobenzoyl derivative of glibenclamide,
      N3-[3H]33055, exclusively labeled a 33-kDa protein. Solubilization of beta-cell
      tumor membranes led to a shift of specific [3H]glibenclamide-binding from the 140
      kDa to the 65-kDa protein, exclusively and to an increased labeling of the 65-kDa
      protein by [3H]glimepiride. The labeling of a unique protein is in agreement with
      similar Kd-values for binding to the sulfonylurea receptor measured for both
      sulfonylureas upon solubilization of beta-cell membranes. Photoaffinity labeling
      of intact cultured beta-cells led also to labeling of a 140-kDa protein by
      [3H]glibenclamide and of a 65-kDa protein by [3H]glimepiride. These studies
      suggest that the beta-cell sulfonylurea receptor consists of at least two protein
      subunits of M(r) 140,000 and 65,000 which bind sulfonylureas of different
      structure with different binding affinities and kinetic parameters. Furthermore,
      the exchange rate of a sulfonylurea determines the insulin releasing activity in
      vitro more closely than the binding affinity.

PMID- 8529522
TI  - The beta-cell response to oral hypoglycemic agents.
AB  - This review describes the role of sulfonylureas and ATP-sensitive K channels
      (KATP) in controlling glucose-induced membrane electrical activity in pancreatic
      beta-cells. The glucose-dependent pathway, the most important both
      physiologically and pathophysiologically, is contrasted with other pathways for
      non-nutrient beta-cell modulators. KATP channels, the links between beta-cell
      metabolism and membrane electrical activity, are regulated in complex ways by
      nucleotide phosphates and a number of clinically important pharmacological
      agents. Recent cloning of the islet sulfonylurea receptor and KATP channel should
      lead to answers to important questions raised by 25 years of beta-cell
      electrophysiology.

PMID- 8529523
TI  - Potassium channels in the cardiovascular system.
AB  - In vitro and in vivo studies suggest that opening of ATP-sensitive potassium
      channels following ischaemia enhances recovery of myocardial contraction, dilates
      blood vessels and has an antiarrhythmic effect. Different sulphonylurea compounds
      that block the ATP-sensitive potassium channels exert different effects on
      cardiac functions. Glibenclamide decrease, arrhythmogenesis during acute
      myocardial infarction in rats and reduces strophanthin cardiotoxicity in rabbits.
      Other sulphonylurea compounds, but not glibenclamide, increase arterial blood
      pressure and myocardial contractility. These effects may be partly secondary to
      blockade of ATP-sensitive potassium channels and partly due to independent
      cardiac and extracardiac actions. Glimepiride may have a more advantageous
      cardiovascular effect than glibenclamide. The studies suggest the hypothesis that
      deleterious cardiovascular effects of some hypoglycaemic sulphonylurea drugs may
      contribute to the high cardiovascular mortality rate in diabetes mellitus. An
      observational study suggested glibenclamide decreased the incidence of fatal
      myocardial infarction and development of ventricular fibrillation in patients
      suffering from acute myocardial infarction. Glibenclamide may also decrease the
      incidence of ventricular ectopic beats in digitalized patients compared with
      other sulphonylurea compounds. The studies suggested the survival of subjects
      treated with glibenclamide, insulin, or diet alone after the first attack of
      angina pectoris or after first acute myocardial infarction may be longer compared
      with those on other sulphonylurea therapies. Further large scale prospective,
      randomised studies are needed to determine whether the reported effects can be
      verified and are sufficiently large to affect clinical prescribing.

PMID- 8529524
TI  - CACN4, the major alpha 1 subunit isoform of voltage-dependent calcium channels in
      pancreatic beta-cells: a minireview of current progress.
AB  - Calcium influx through L-type voltage-dependent calcium channels (VDCCs) triggers
      insulin secretion. Until recently, the structure of VDCCs in pancreatic beta
      cells and their regulation in altered metabolic states were not known. Study of
      the VDCC protein in skeletal muscle has shown that the alpha 1 subunit is
      functionally the most important subunit among the five subunits (alpha 1, alpha
      2, beta, gamma and delta), acting as a voltage sensor and an ion-conducting pore.
      Molecular cloning of a novel alpha 1 subunit (beta-cell/neuroendocrine type,
      CACN4) of VDCCs from pancreatic islets and insulinoma have made it possible to
      study the electrophysiological and pharmacogical properties, regulation, and
      genetics of the VDCCs expressed in beta-cells. The CACN4 is structurally related
      to other members of the VDCC alpha 1 subunit family, including skeletal muscle,
      cardiac, and brain types. In situ hybridization experiments reveal that CACN4
      mRNAs are expressed in beta-cells in the islets. Heterologous expression studies
      show that CACN4 in the presence of the beta subunit elicits L-type VDCC currents,
      although expression of CACN4 alone is not sufficient for VDCC activity. Studies
      of animal models with chronic hyperglycemia and starvation have indicated that
      the reduced CACN4 mRNA levels in pancreatic islets are associated with impaired
      insulin responses to stimuli in both hyperglycemic and fasting states. These
      studies demonstrate that CACN4 is the major component of VDCCs in pancreatic beta
      cells and suggest that it plays a crucial role in the regulation of insulin
      secretion in normal and altered metabolic states.

PMID- 8529525
TI  - In vitro activity of E-4868, a new fluoroquinolone with a 7-azetidin ring,
      compared with ciprofloxacin, ofloxacin and fleroxacin.
AB  - E-4868, (-)-7[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4
      dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid, is a new fluoroquinolone with
      a 7-azetidin ring substituent. The in vitro activity against clinical isolates
      was compared with that of ciprofloxacin, ofloxacin and fleroxacin. In general,
      activity of E-4868 against aerobic and facultative anaerobic Gram-negative
      bacilli was equal to or slightly less active than ciprofloxacin with the
      exception of Morganella morganii and Proteus spp., E-4868 MIC90, 1 and 0.5
      microgram/ml, respectively. E-4868 activity was two- to eight-fold higher than
      ciprofloxacin against Gram-positive cocci. For anaerobic species, E-4868 activity
      was comparable to that of ciprofloxacin, although against the Bacteroides
      fragilis group E-4868 was four-fold more active than ciprofloxacin.

PMID- 8529526
TI  - Outer membrane alterations in Pseudomonas aeruginosa after five-day exposure to
      quinolones and carbapenems.
AB  - A Pseudomonas aeruginosa strain (P.aeruginosa), recently isolated in clinical
      practice, was tested to evaluate the changes induced in the minimal inhibitory
      concentration (MIC) values and in the outer membrane (OM) components by a five
      day exposure to sub-MIC concentrations of the quinolones ciprofloxacin and PD
      131.628 and the carbapenems imipenem and meropenem. The treated strain showed a
      thirty two-fold increase in MIC values for quinolones and a sixteen-fold increase
      for carbapenems. The electrophoretic profile of the OM proteins of the strain
      treated with quinolones showed that ciprofloxacin induces loss of the 47 Kd
      protein band, whereas PD-131.628 modifies the protein pattern of the strain only
      after five days of exposure. The carbapenems engendered disappearance of the same
      protein band. Qualitative lipopolysaccaride (LPS) analysis did not reveal any
      change after antibiotic treatment of the strain, whereas the 2-keto-3
      deoxyoctonic acid (KDO) assay showed considerable reduction in the strain treated
      with sub-MIC doses of meropenem. It can therefore be safely stated that the D2
      protein plays an important though not exclusive role in enhancing strain
      resistance against the two classes of antibiotics tested in our study.

PMID- 8529527
TI  - Antiarrhythmic effect related to the plasma concentration of pentisomide in vivo
      and the antiarrhythmic-concentration relationship in vitro.
AB  - Pentisomide, 2-(2-diisopropylaminoethyl)-4-methyl-2-(pyridyl)- pentanamide, is a
      novel antiarrhythmic agent structurally related to disopyramide. Using a glass
      bead arrhythmic model, the authors studied the antiarrhythmic effect of
      pentisomide in dogs by monitoring the plasma concentrations. When pentisomide was
      infused at 1 mg/kg/min for 20 min, the ventricular tachycardia was significantly
      reduced at 5 min after starting the infusion; the arrhythmias were reduced to
      less than 5% at the end of the 20 min infusion. The plasma-free concentration of
      pentisomide was about 3 micrograms/ml at 5 min; it increased to about 10
      micrograms/ml at the end of 20 min infusion. With 0.3 mg/kg/min infusion, the
      arrhythmias were reduced to about 60% but were not significant at 20 min of
      infusion. The plasma-free concentration of pentisomide did not reach 3
      micrograms/ml until 20 min of infusion. The 3 micrograms/ml plasma-free
      concentration for pentisomide seems to be a critical concentration in inducing a
      significant antiarrhythmic effect. Pentisomide dose-dependently inhibited
      ischaemia-reperfusion arrhythmia at doses of 30 microM and higher concentrations
      in vitro. In conclusion, pentisomide inhibits arrhythmias dependent with the
      plasma concentration or with the concentration of the external solution. The
      critical plasma-free concentration for inhibition of arrhythmias was 3
      micrograms/ml (not equal to 10 microM) and the in vitro effect also had a similar
      concentration. Therefore, the in vivo and in vitro antiarrhythmic concentrations
      were well correlated.

PMID- 8529528
TI  - The influence of antineoplaston A5 on particular subtypes of central dopaminergic
      receptors.
AB  - A new therapeutic strategy for the treatment of Parkinson's disease (PD) is based
      on providing trophic support for degenerating dopaminergic (DA) neurons. It can
      be accomplished by administration of neurotrophic factors, or inducing astrocytes
      to differentiate and produce such factors. Antineoplaston A5 (A5), which is a
      naturally-occurring cytodifferentiating agent, may induce astrocytes to undergo
      normal differetiation, produce neurotrophic factors and alleviate the symptoms of
      PD. This paper describes studies on the influence of A5 on subtypes of central DA
      receptors by measuring the potency of haloperidol catalepsy in rats. A5, D1
      agonist, and D1 D2 antagonists were given i.p. and D2 agonist s.c. for three
      consecutive days. Haloperidol catalepsy was measured by the method of Costall and
      Nylor. The degree of catalepsy was assessed every 30 min for 24 h and
      statistically evaluated using the Student's t-test. The results confirmed that A5
      significantly attenuated catalepsy and stimulates dopamine D2 receptors. It
      reverses catalepsy induced by haloperidol and D2 antagonists, but increases
      cataleptogenic activity if given in combination with the D2 agonist. This leads
      to the conclusion that A5 as a naturally-occurring agent neutralizes both hyper-
      and hypoactivity of central dopaminergic structures. Besides possible use as an
      antiparkinsonism agent, A5 may find application in the treatment of other
      disturbances of dopaminergic transmission.

PMID- 8529529
TI  - Carnitine supplementation in human idiopathic asthenospermia: clinical results.
AB  - On the basis of reported experimental and clinical studies we investigated the
      effectiveness of L-carnitine administration in a group of patients with
      idiopathic asthenospermia. A favourable effect of the compound on sperm motility
      and rapid linear progression has been shown in 37 out of 47 patients treated. In
      addition, the total number of sperms increased. L-carnitine was supplemented
      orally by a daily dosage of 3 g for three months.

PMID- 8529530
TI  - Effects of zolpidem on the architecture and cyclical structure of sleep in poor
      sleepers.
AB  - Effects of zolpidem, a short acting non benzodiazepine hypnotic, have been
      studied in eight female poor sleepers, aged 25 to 54 years, documented during two
      consecutive adaptation nights. Subjects were recorded according to a 22 day
      single blind study. Placebo was given orally at bedtime on nights 2-4, zolpidem
      on nights 5-20 and finally placebo on nights 21-22. Polygraphic recordings
      (conventional analysis) were performed on nights 1-6; 12, 13; 19-22. Parameters
      of sleep continuity, sleep architecture and cyclical structure of sleep were
      studied. Zolpidem 10 mg showed a hypnotic effect on poor sleepers. It reduced
      sleep latency, increased total sleep time and decreased the number of awakenings
      during all recorded nights. During the first post-drug night a rebound insomnia
      was observed in two subjects only. Zolpidem did not increase specifically stage 2
      to the detriment of stages 3 and 4 but it restored them during the first nights
      of administration. Study of the rapid eye movements-non rapid eye movements (REM
      NREM) sleep cycles structure showed that the increase of stages 3 and 4 occurred
      only during the first part of the night. Finally, zolpidem had no effect on REM
      sleep temporal distribution.

PMID- 8529531
TI  - DSM-III-R alcohol abuse and dependence and psychiatric comorbidity in Ontario:
      results from the Mental Health Supplement to the Ontario Health Survey.
AB  - The lifetime prevalence of DSM-III-R alcohol abuse and alcohol dependence and
      associated patterns of psychiatric comorbidity in the Ontario population aged 15
      64 years are estimated from a survey of a representative household sample using
      the University of Michigan Composite International Diagnostic Interview (UM
      CIDI). More than half (55%) of all individuals with an alcohol disorder have a
      lifetime comorbid disorder and comorbidity is more common in women than in men
      with an alcohol disorder. The odds of having other drug disorders and antisocial
      personality disorder are very high in individuals with an alcohol disorder
      compared to those without. Alcohol dependents, but not alcohol abusers, have
      significantly increased odds of mood and anxiety disorders compared to
      individuals without an alcohol disorder. Sociodemographic risk profiles, alcohol
      use patterns and course differ for alcohol abusers/dependents with and without a
      comorbid disorder. Primary anxiety and drug disorders are risk factors for
      subsequent alcohol disorders.

PMID- 8529532
TI  - Common genetic mechanisms in alcohol, drug, and mental disorder comorbidity.
AB  - Comorbid drug and mental disorders were assessed in 63 monozygotic (MZ) and 67
      dizygotic (DZ) twin pairs. DSM-III alcohol dependence was heritable in males when
      probands had a comorbid DSM-III drug or mental disorder but not when probands had
      only alcohol dependence. For males, significantly higher cross-MZ than cross-DZ
      correlations were found between alcohol dependence in probands and certain mental
      and drug disorders in cotwins. In contrast, females showed higher within-twin
      than cross-MZ correlations and similar cross-MZ and cross-DZ correlations between
      alcohol dependence and all mental and drug disorders. These results suggest
      comorbidity between alcohol and certain drug and mental disorders in males in
      epidemiological surveys may be due in part to genetic influences.

PMID- 8529533
TI  - DSM-III, DSM-IV and ICD-10 as severity scales for drug dependence.
AB  - The construct of illness severity serves many scientific and clinical functions.
      This study tested the performance as severity scales of three systems for
      diagnosing drug dependence--DSM-III, DSM-IV and ICD-10--in a multisite regional
      sample of 370 clinical subjects. Both lifetime and current severity of four drug
      problems--alcohol, cannabis, cocaine and opiate dependence--was studied in three
      stages: (a) item difficulty and internal consistency analysis; (b) probabilistic
      modeling of distribution behavior; and (c) concurrent validation against a set of
      independent measures. All three systems, for most drugs correlated with most test
      variables, had good to excellent concurrent validity. Unexpectedly, DSM-III
      showed in some instances better item behavior, composite score behavior and
      concurrent validity than the other systems, though DSM-IV and ICD-10 are based on
      slimmer generic algorithms, and may represent a good balance between simplicity
      and concurrent validity. Results suggest that the design of future diagnostic
      algorithms start at the item level and strive for moderate levels of both
      internal consistency and difficulty. Composite score distributions can then be
      modeled in field research, and necessary item corrections can be made before the
      algorithm is widely promulgated.

PMID- 8529534
TI  - Assessment of nalmefene glucuronide as a selective gut opioid antagonist.
AB  - Opioid use often causes troublesome constipation as a side-effect. Selective
      antagonism of the intestinal actions of opioids might be useful in the treatment
      of opioid-induced constipation. We tested the inactive metabolite of nalmefene,
      nalmefene glucuronide, which showed promise of gut selectivity in rodent models,
      by administering ascending doses in single-blind, placebo-controlled fashion to
      five methadone-maintained, opioid-dependent male volunteers. Assessment of
      whether systemic or gut-selective opioid antagonist effects occurred was measured
      by vital signs, pupillary diameter, opioid withdrawal symptom scales, and bowel
      function. Oral nalmefene glucuronide precipitated symptoms and signs consistent
      with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after
      dosing. We conclude that nalmefene glucuronide does not appear to exert
      sufficient gut selectivity to be useful in antagonizing constipation due to
      exogenous opioid administration without antagonizing systemic opioid effects.

PMID- 8529536
TI  - alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit
      methamphetamine synthesis: pharmacological evaluation and interaction with
      methamphetamine.
AB  - Methamphetamine is a popular drug of abuse, readily synthesized in clandestine
      laboratories. Illicitly obtained methamphetamine is frequently impure, containing
      various purposefully added diluents and adulterants, as well as impurities of
      manufacture and origin. Few impurities have been studied in vivo and limited
      information exists concerning their pharmacology/toxicology. One such impurity of
      manufacture is alpha-benzyl-N-methylphenethylamine (BNMPA). Acute toxicity and
      spontaneous activity (locomotor) studies were conducted with this compound alone
      and in combination with S(+)-methamphetamine (METH) in male, ICR mice. In the
      acute toxicity studies, BNMPA was evaluated for convulsant activity. While BNMPA
      also produced some behavioral disturbances similar to those seen with
      methamphetamine (e.g., stereotopy) at doses greater than 30 mg/kg, no tonic
      clonic convulsions were noted until pre-terminal convulsion at 50 mg/kg. METH
      alone produced tonic-clonic convulsions at terminal doses of 70 mg/kg. When BNMPA
      was given in combination with METH, there was no readily apparent change in the
      convulsion profile from that of METH given alone. In spontaneous activity
      studies, doses of BNMPA ranging from 1 mg/kg to 50mg/kg failed to alter locomotor
      activity significantly from controls though 5 mg/kg METH alone significantly
      increased spontaneous activity. In addition, increases in spontaneous activity
      elicited by 5 mg/kg METH were not affected when METH was given with 5 mg/kg
      BNMPA. While BNMPA appears to have toxic effects in the central nervous system
      (CNS), the failure to affect locomotor activity or alter either METH-induced
      increases in spontaneous activity or METH-induced convulsions suggests that the
      two agents are producing their effects through distinct mechanisms.

PMID- 8529535
TI  - Pathological gambling among methadone patients.
AB  - This paper examines the correlates of problem gambling among a population of 220
      methadone patients receiving treatment in the New York metropolitan area. Like
      most methadone patients, respondents were primarily adult males, ethnically
      mixed, of limited educational accomplishment and had long experiences with
      intravenous drug use. More than two-thirds of subjects had been convicted of one
      or more criminal offences. Analysis of the data showed seven percent of
      respondents to be probable pathological gamblers according to the South Oaks
      Gambling Screen (SOGS), indicating a high rate of gambling problems among this
      treatment population. Consistent with past studies, problem gamblers are more
      likely to be men, with histories of alcohol abuse, and with extensive criminal
      participation dating back to their teenage years. The data also suggested that
      problem gamblers who were also drug dependent were more likely to show greater
      evidence of social dysfunctionality compared to those who were exclusively
      substance abusers. More dually addicted respondents reported higher levels of
      recent heroin use, greater unemployment, and more reported hallucinations.
      Probable pathological gamblers who were substance abusers were also more likely
      to report being in conflict with their close friends. A multiple regression
      analysis suggested this to be the closest linked correlate to being a
      pathological gambler. Evidently, pathological gamblers create antipathy towards
      themselves as their compulsion to gamble is expressed; this in turn, may drive
      them toward further gambling, as they respond to this perceived opposition. These
      last preliminary findings will require further confirmation in future research.

PMID- 8529537
TI  - Validity of intravenous drug abusers' self-reported changes in HIV high-risk drug
      use behaviors.
AB  - The HIV-1 high-risk drug use behavior of intravenous drug abusers was assessed
      both retrospectively (for 6 months) and prospectively (for 6 months) via
      structured interview and urinalysis testing. Subjects were 281 intravenous drug
      abusers, 146 enrolled in outpatient methadone treatment (Treatment group) and 135
      not in treatment (Community group). The Treatment group reported fewer drug
      injections and less needle sharing and had fewer positive urinalyses for opiates
      and cocaine than did the Community group. Reported drug injection and needle
      sharing declined over time, and an increasing proportion of subjects reported
      abstinence from these behaviors. In contrast to the behavioral reports of
      subjects, positive urinalyses indicating opiate and/or cocaine use did not
      decline over time. Almost half (45.8%) of the reported increase in injection
      abstinence from intake to month six was disconfirmed by urinalysis. In contrast
      to this large discrepancy regarding reported behavior change, there was good
      agreement between reported injection abstinence and urinalysis results at single
      points in time. These data indicate that the validity of the reported HIV-1 risk
      behavior change of drug abusers may be less than that of reported risk behavior
      occurrence. The data raise important questions about the validity of reported
      reductions in high-risk drug use behaviors, and indicate the importance of using
      biological indicators of HIV-1 risk behavior (such as urinalysis) whenever
      possible.

PMID- 8529538
TI  - Construct validity of the abuse-dependence distinction as measured by DSM-IV
      criteria for different psychoactive substances.
AB  - This article used the diagnostic criteria of the Diagnostic and Statistical
      Manual-Fourth Edition (DSM-IV) to compare the validity of a qualitative and a
      quantitative model of the abuse-dependence distinction for different psychoactive
      substances in samples of drug users drawn from drug treatment inpatients, general
      psychiatric patients, and the community. The hypothesis that DSM-IV abuse
      criteria differ from dependence criteria in kind rather than degree (a
      qualitative model) was only occasionally supported by confirmatory factor
      analyses of DSM-IV diagnostic criteria, by patterns of correlations of the two
      kinds of criteria with Addiction Severity Score (ASI) composites and measures of
      frequency of substance abuse, and by concurrent/prognostic validity analyses.
      However, the findings were consistent with a quantitative model of the abuse
      dependence distinction that posits that abuse is a mild form of dependence.
      Whether abuse and dependence categories of users were established from separate
      DSM-IV criteria for abuse and dependence or from scores from a severity-of
      dependence scale based on the pooled DSM-IV dependence and abuse criteria,
      abusers generally used drugs less than users in the dependence category and
      reported less problems associated with substance abuse on the ASI.

PMID- 8529539
TI  - The management of hyperactive children.

PMID- 8529540
TI  - Alprostadil for erectile impotence.

PMID- 8529541
TI  - Benzamycin gel for acne.

PMID- 8529542
TI  - Myringitis.

PMID- 8529543
TI  - Cat allergy.

PMID- 8529544
TI  - The current status of expanded polytetrafluoroethylene (Gore-Tex) in facial
      plastic surgery.

PMID- 8529545
TI  - Laryngeal granulomas of the false vocal fold.

PMID- 8529546
TI  - Lateral lamella of the cribriform plate--an important high-risk area in
      endoscopic sinus surgery.

PMID- 8529547
TI  - Audiogram construction using frequency-specific auditory brainstem response (ABR)
      thresholds.
AB  - Brainstem evoked response audiometry (ABR) permits auditory pathway assessment
      without the need for voluntary response. Brainstem responses are unaffected by
      attention, drugs, and most other confounding conditions. Consequently, if ABR
      could be used to determine hearing threshold in the speech frequencies, it would
      have great value for patients who are unable or unwilling to respond accurately
      during behavioral audiometric testing. Utilizing broad band clicks, one can only
      estimate hearing sensitivity in the frequency range of 2,000 to 4,000 Hz. This is
      inadequate for medical or legal purposes in which hearing in the speech
      frequencies must be assessed. Consequently, we have developed a modified ABR
      technique that permits a more accurate determination of hearing threshold at 500,
      1,000, 2,000 and 3,000 Hz, as illustrated in tests on 27 normal ears. This
      technique has great potential value for neonatal and mentally handicapped
      populations, as well as for individuals involved in hearing loss litigation.

PMID- 8529548
TI  - Retropharyngeal abscess: clinical review.
AB  - Retropharyngeal abscess, once a relatively common entity in children, is uncommon
      today. From 1981 to 1991, we treated 20 cases. Abscesses secondary to upper
      respiratory infection in children were seen only in three (15%) cases. Trauma and
      foreign bodies were the most common etiologic factors in the adult subgroup.
      Streptococcus viridans and Klebsiella pneumoniae were the most common pathogens.
      The use of contrast-enhanced computed tomography has had a significant impact on
      the diagnostic work-up. The choice of initial antibiotic therapy is discussed.
      There were no deaths in this series.

PMID- 8529549
TI  - The use of addition reaction silicone materials in the fabrication of ear plugs.
AB  - Ear plugs are currently recommended for patients with tympanostomy tubes or for
      those requiring noise attenuation. Most techniques used today require a two-step
      process involving an impression of the ear followed by laboratory fabrication
      from a cast. This paper presents an alternative technique which is accomplished
      in one appointment and eliminates the laboratory phase by using addition reaction
      silicones. The indications for ear plugs and clinical results achieved with this
      new technique were also reviewed.

PMID- 8529550
TI  - Functional parathyroid cyst and hypocalciuric hypercalcemia.
AB  - Parathyroid cysts are uncommon. They can be divided into functional and
      nonfunctional cysts depending on whether or not they are associated with
      hypercalcemia. Functioning cysts are very rare, with fewer than twenty reported
      cases. We report a case of functioning parathyroid cyst associated with
      hypocalciuric hypercalcemia. We have been unable to find a similar case
      previously reported in the literature.

PMID- 8529551
TI  - Malignant oncocytoma of the lacrimal sac: ultrastructure and immunocytochemistry.
AB  - Malignant oncocytoma of the lacrimal sac is a rare tumor. A third example is
      presented here. In addition to oncocytes, tumor acini also harbored a few mucin
      cells and myoepithelial cells. The presence of immunoreactive lactoferrin and
      secretory piece suggested a resemblance to parotid acinic cell carcinomas. The
      difference was marked by a compact acinar structure and myoepithelial cell
      differentiation in the oncocytoma.

PMID- 8529552
TI  - Uvulectomy in the office setting.
AB  - Snoring is a common problem which affects 50% of male and 30% of female patients.
      In a small number of patients, partial uvulopalatoplasty in the office setting
      has been found to ameliorate loud snoring. In our study, 28 patients had
      uvulectomy for snoring, 17 of whom responded to our survey. The procedure was
      somewhat beneficial (rated 3.2 on a scale of 10, with 10 representing no snoring)
      and had little impact on quality of life (rated 2.7 on a scale of 10, with 10
      representing great improvement). After the procedure patients had considerable
      pain (rated 7.4 on a scale of 10, with 10 representing excruciating pain) which
      lasted > 10 days in 35% and led to a mean of 2.9 missed work days. There were no
      complications. Fourteen of 17 patients wanted additional treatment to reduce
      snoring.

PMID- 8529553
TI  - Spatio-temporal decomposition of the EEG: a general approach to the isolation and
      localization of sources.
AB  - The principal-component method of source localization for the background EEG is
      generalized to arbitrary spatio-temporal decompositions. It is shown that as long
      as the spatial patterns of the decomposition span the same signal space as the
      principal spatial components, the computational process of attempting to localize
      the sources is the same. Decompositions other than the principal components are
      shown to be superior for the EEG in that they appear to enable individual sources
      to be better isolated. An example is given using the common spatial pattern
      decomposition and using a raw varimax rotation of a subset of the common spatial
      patterns. The results show that the principal component decomposition is almost
      ineffective for isolating spike and sharp wave activity in an EEG from a patient
      with epilepsy, that the common spatial pattern decomposition is significantly
      better and that the varimax rotation is better yet. That the varimax rotation is
      best is demonstrated by attempting to locate dipole sources inside the brain
      which account for the spike and sharp wave activity on the scalp. The question
      which remains is whether there exists some oblique rotation of the basis vectors
      of the EEG signal space which is optimal for isolating individual sources.

PMID- 8529554
TI  - Neuromagnetic source imaging with FOCUSS: a recursive weighted minimum norm
      algorithm.
AB  - The paper describes a new algorithm for tomographic source reconstruction in
      neural electromagnetic inverse problems. Termed FOCUSS (FOCal Underdetermined
      System Solution), this algorithm combines the desired features of the two major
      approaches to electromagnetic inverse procedures. Like multiple current dipole
      modeling methods, FOCUSS produces high resolution solutions appropriate for the
      highly localized sources often encountered in electromagnetic imaging. Like
      linear estimation methods, FOCUSS allows current sources to assume arbitrary
      shapes and it preserves the generality and ease of application characteristic of
      this group of methods. It stands apart from standard signal processing techniques
      because, as an initialization-dependent algorithm, it accommodates the non-unique
      set of feasible solutions that arise from the neuroelectric source constraints.
      FOCUSS is based on recursive, weighted norm minimization. The consequence of the
      repeated weighting procedure is, in effect, to concentrate the solution in the
      minimal active regions that are essential for accurately reproducing the
      measurements. The FOCUSS algorithm is introduced and its properties are
      illustrated in the context of a number of simulations, first using exact
      measurements in 2- and 3-D problems, and then in the presence of noise and
      modeling errors. The results suggest that FOCUSS is a powerful algorithm with
      considerable utility for tomographic current estimation.

PMID- 8529555
TI  - The complementary relationship between waking and REM sleep in the oculomotor
      system: an increase of rightward saccades during waking causes a decrease of
      rightward eye movements during REM sleep.
AB  - Since an inverse relationship between waking and REM sleep eye movements (EMs)
      has been found with respect to frequency, amplitude and direction of EMs, we
      evaluated variations in the percentages of horizontal rapid eye movements (REMs)
      during REM sleep after having increased rightward saccades during waking by means
      of a unilateral tachistoscopic visual test administered prior to sleep. In
      another condition subjects were given the same 4 h testing condition prior to
      sleep, the only difference being that they were instructed not to move their
      gaze; therefore only "attentional movements" were possible. This condition served
      as a control for the role of oculomotor activity in the complementary
      relationship between waking and REM sleep eye movements. The actual increase of
      rightward saccades during waking resulted in a significant decrease of rightward
      REMs. This effect has been observed only in the condition in which rightward eye
      movements were increased and it is specific for REMs of amplitude similar to
      those which were increased during waking by the lateralized test.

PMID- 8529556
TI  - Electroclinical significance of rolandic spikes and dipoles in
      neurodevelopmentally normal children.
AB  - "Centrotemporal" (rolandic) spikes are elemental to the diagnosis of benign
      rolandic epilepsy (BRE) and may reveal a characteristic dipole distribution. Yet,
      not all children with rolandic spikes present with clinical seizures. Using
      additional scalp coverage according to the 10-10 electrode system, we attempted
      to correlate 2 specific spike features: (a) dipole fields, and (b) exact location
      of maximum negativity, with the presence or absence of clinical seizures in 42
      neurodevelopmentally normal children with rolandic (central) spikes. Thirty-three
      (79%) presented with seizures. Seventeen of 21 children revealing dipoles (81%)
      and 16 of 21 patients without dipoles (74%) had seizures. Children with high
      central (C3/C4) foci were just as likely to present with seizures (10 of 15, 67%)
      as were those with low central (C5/C6) foci (23 of 27, 85%) (P > 0.10). The
      majority of our study subjects (27 of 42, 64%) revealed maximum negativity in the
      low central region (C5/C6), and the dipole feature was as likely to be associated
      with high central foci (7 of 15, 47%) as with low central foci (14 of 27, 52%).
      Although rolandic spikes are a reliable indicator of potential epileptogenicity,
      neither their exact location nor dipolar distribution help to further define the
      population with clinical seizures.

PMID- 8529557
TI  - Incidence of photosensitive epilepsy: a prospective national study.
AB  - We undertook a prospective nationwide study to determine the incidence of
      photosensitive epilepsy (PE). Virtually all EEG departments in Great Britain
      (providing approximately 90% coverage of all EEGs performed on people with newly
      diagnosed seizures) screened cases referred to them over a 3 month period and
      identified all new cases of epilepsy (defined as one or more recognised seizures)
      whose first EEG showed a photoparoxysmal response (PPR) on intermittent photic
      stimulation (IPS). 191 cases were identified, 143 of whom had type 4 PPRs
      (generalised spike and wave on IPS) on their first EEG. The annual incidence of
      cases of epilepsy with type 4 PPRs on their first EEG was conservatively
      estimated to be 1.1 per 100,000, representing approximately 2% of all new cases
      of epilepsy. When restricted to the age range 7-19 years, the annual incidence
      rose to 5.7 per 100,000-approximately 10% of all new cases of epilepsy presenting
      in this age range. To ascertain if there was a significant seasonal variation in
      PE, 5 EEG departments (which together contributed 15% of cases in the first study
      period) were visited during a second 3 month study period to identify all new
      cases of epilepsy with type 4 PPRs on their first EEG. No significant seasonal
      variation in incidence between summer and winter was found.

PMID- 8529558
TI  - Intracerebral recordings of slow potentials in a contingent negative variation
      paradigm: an exploration in epileptic patients.
AB  - While exploring epileptic patients with intracerebral multilead electrodes, we
      applied a forewarned reaction time task with two successive sound stimuli, a
      paradigm that is known to elicit a contingent negative variation (CNV). The
      second, imperative sound stimulus was followed by a hand or a foot movement.
      Eleven patients suffering drug-resistant partial epilepsies were tested. The slow
      potentials developing during the time between the two stimuli were usually not
      typical CNVs (sometimes comprising multiple successive components with distinct
      polarities). Such "CNV-like" potentials were obtained from two main cortical
      zones: a central one including premotor, motor, supplementary motor, postcentral
      and cingulate areas; and a temporal zone, mainly including the auditory cortex
      and its vicinity, and in some cases the amygdala. This restricted localization
      contrasted with the broader extent of the CNVs on the scalp. Intracerebral CNV
      like events were obtained from both hemispheres, independent of the side of the
      performed movement. In some patients, readiness potentials (RPs) were also
      recorded for comparison and displayed a more restricted extent, being present
      only on the contralateral motor cortex and bilaterally in the supplementary motor
      areas. Our data suggest that the last part of the CNV cannot just be identified
      with the RP.

PMID- 8529559
TI  - ERP signs of early selective attention effects to check size.
AB  - In ERP literature on visual selective attention evidence has been provided that
      selectively directing attention to a spatial frequency affects the visual
      processing of the attended frequency, and of unattended frequencies within the
      same channel bandwidth, starting at a relatively late level of post-stimulus
      processing, i.e., after about 150 msec. Nevertheless, little knowledge is
      available about the topographic distribution of these attention effects. This
      study investigated attentional selection of stimulus relative size at occipital
      and latero-occipital sites, as well as at fronto-lateral sites. ERPs from
      posterior scalp electrode sites showed that attention to check sizes enhanced the
      early sensory components, thus indicating that feature-based attention may result
      in a modulation of sensory processing. Comparisons of the ERPs to relevant and
      irrelevant patterns showed an enhanced latero-occipital P90 positivity as well as
      an occipital N115 negativity to relevant patterns, thus also suggesting possible
      differential mechanisms of early attentional selectivity at these locations.
      Later effects of attention consisted of a selection negativity to relevant
      patterns at posterior electrodes, and a selection positivity at latero-frontal
      sites. A larger late positivity to irrelevant patterns at anterior sites also
      suggested an active suppression of attentional response to irrelevant
      information. Moreover, right-and left-sided asymmetries were found to be
      respectively consistent for the P90 and N115 with left hemispheric specialization
      for high, and right hemispheric specialization for low spatial frequencies. A
      stronger left-sided attentional selectivity has also been found.

PMID- 8529560
TI  - Olfactory event-related potentials in normal human subjects: effects of age and
      gender.
AB  - Behavioral and electrophysiological testing of olfactory function was performed
      in 33 normal human male and female subjects, 18-83 years of age. Acuity for odor
      identification and odor detection was verified by standard psychophysical tests.
      For evoked potential testing, a constant flow olfactometer provided odorant
      stimuli (amyl acetate) or air control stimuli that were presented to the right
      nostril by a nasal cannula at a flow rate of 5 l/min, duration of 40 msec and
      random interstimulus intervals of 6-30 sec. The behavioral tests revealed no
      significant difference between males and females, whereas increasing age was
      associated with a decline in performance on the odor identification test. No
      reproducible evoked potentials were recorded in response to the air control
      stimulus. Potentials to the odorant stimulus consisted of 4 components named P1,
      N1, P2 and N2. A significant correlation was found between P2 latency and odor
      identification test scores, suggesting a relationship between the generation of
      the P2 component and olfactory processing. P2 peak latency increased
      significantly with age at 2.5 msec/year. An age-related decline in N1-P2
      interpeak amplitude was seen in male subjects. Topographic differences were seen
      in the P2 peak amplitude and the N1-P2 and P2-N2 interpeak amplitudes such that
      their amplitudes were greatest at Cz and Pz. On average, N1-P2 interpeak
      amplitudes were larger in the female subjects than in the male subjects, possibly
      revealing a hormonal influence on the olfactory event-related potential.

PMID- 8529561
TI  - Interrater reliability of the multiple sleep latency test.
AB  - The purpose of this study was to evaluate interrater reliability in the
      interpretation of the multiple sleep latency test (MSLT). We prospectively
      analyzed MSLTs performed on 21 patients with excessive daytime sleepiness. MSLTs
      were recorded on Grass Model 78 polygraphs with EEG, electro-oculogram, and chin
      EMG. Each test was performed simultaneously at paper speeds of 10 and 30 mm/sec
      and was scored blindly by 3 readers using standard criteria. For the quantitative
      variable (sleep latency), a LISREL model was used. For the binary variable (REM
      present or not), a kappa coefficient was used. Interrater reliability of sleep
      latency was 0.850 at speed 10, and 0.884 at speed 30. There was no significant
      difference between speed 10 and 30. Interrater reliability for the presence or
      absence of REM was 0.515-0.563 at speed 10, and 0.447-0.525 at speed 30. On the
      MSLT, the estimation of sleep latency showed excellent consistency between
      different readers. The determination of the presence or absence of REM only
      showed fair to good agreement among observers. There was no significant
      difference between a paper speed of 10 vs. 30 mm/sec.

PMID- 8529562
TI  - [The serotonin syndrome: review of the literature and description of an original
      study].
AB  - In animals the occurrence of a behavioural syndrome consisting of hyperactivity,
      stereotyped movements and increase of temperature has been induced by MAOIs, 5-HT
      precursors (L-tryptophan) and 5-HT reuptake inhibitors. Most of these
      manifestations were specifically blocked by a pretreatment with an inhibitor of
      serotonin synthesis. In humans, the association of myoclonus, diarrhea,
      confusion, hypomania, agitation, hyperreflexia, shivering, incoordination, fever
      and diaphoresis, when patients are treated with serotoninergic agents, could
      constitute a "serotonin syndrome". Such cases of serotonin syndrome were reported
      after treatments with L-tryptophan, MAOIs, serotonin reuptake inhibitors and
      tricyclics alone or in association. The authors prospectively evaluated all the
      "serotonin-related" symptoms in 38 depressed inpatients fulfilling DSM III-R
      criteria of major depression. 16 (42%) out of 38 patients presented at least one
      symptom of serotonin syndrome. In 14 cases tremor and myoclonus occurred
      simultaneously and 10 patients presented at the same time tremor, myoclonus,
      diaphoresis and shivering. Except for two patients, symptoms were transient,
      lasted less than one week and disappeared with the pursuit of the treatment. Most
      often, serotonin syndrome thus corresponds to a reaction induced by a combination
      of serotoninergic agents at high dosages. In very rare cases, a toxic and
      potentially fatal interaction can occur between MAOIs, tricyclics and selective
      serotonin reuptake inhibitors at therapeutic dosages. Serotonin syndrome also
      provides an heuristic model of the putative mode of action of antidepressants.
      Serotonin-related symptoms are the physical and objective expression of the
      antidepressant-induced increase in serotonin. The specificity of serotonin
      related syndrome also needs to be discussed since most of the symptoms, such as
      tremor and diaphoresis, are not in all cases related to an increase in serotonin.

PMID- 8529563
TI  - [Comorbidity of bipolar and eating disorders. Epidemiologic and therapeutic
      aspects].
AB  - The frequent association of bulimia nervosa and affective disorders is well
      documented. Most studies on this topic have focused on the comorbidity of bulimia
      nervosa and unipolar depression. The literature on the comorbidity of eating
      disorders and bipolar disorder is more sparse. Nevertheless, an increased rate of
      bipolar disorder, especially bipolar II disorder, has been found by several
      epidemiological studies in patients with bulimia nervosa. This association might
      be more frequent in bulimic patients presenting with a severe chronic type of
      eating disorder. The relatives of bulimic patients also display an increased
      morbid risk for bipolar disorder. Although the comorbidity of bulimia and bipolar
      disorder does not appear coincidental, the nosological relationships between
      these two disorders are not perfectly clear. The possible relationships between
      seasonal affective disorders and bulimia nervosa have recently been suggested by
      some epidemiological studies, demonstrating that bulimia may display seasonal
      variations with winter worsening of bulimic symptoms. Eating symptoms are present
      in both winter depression and bulimia nervosa. The carbohydrate craving
      encountered in the former disorder could be compared to "binge eating" in bulimic
      patients. Epidemiological data suggest that winter depression is most frequently
      part of a bipolar II disorder. Few data are available concerning the therapeutic
      implications of the association of bulimia nervosa and bipolar disorder. Some
      case reports of concomitant remission of both disorders with anticonvulsivants or
      lithium salts have been published. However, there are no controlled studies.
      Anticonvulsivants or lithium salts might be indicated in some bulimic patients
      who do not present with a typical bipolar disorder, but who fulfill clinical
      criteria which are potentially predictive of a good response to such medications.

PMID- 8529564
TI  - Depressive symptoms and schizophrenia a psychopharmacological approach.
AB  - The frequency of depression was assessed in 43 chronic schizophrenic patients
      during an acute exacerbation phase of schizophrenia. The dexamethasone
      suppression test was administered to all patients. Depressive symptomatology
      showed a prevalence from 16.3% for moderate symptoms to 23.3% for mild ones.
      Depressive symptoms occurred concurrently with the psychotic picture and resolved
      as the psychosis remitted. Depressive symptoms were not relative to age, sex,
      duration of illness, DST cortisol levels, drug dosages and extrapyramidal side
      effects while basal cortisol levels were negatively correlated with basal
      Hamilton score.

PMID- 8529565
TI  - [Anhedonia in major depression. Comparison of 55 depressed patients with 54
      healthy probands].
AB  - A study on 55 subjects who meet Spitzer's research Diagnosis Criteria of primary
      major depressive disorder and 54 healthy subjects has been conducted to explore
      anhedonia. The two groups were matched concerning the socio-demographic variables
      (sex, age, education level). Anhedonia was rated using the Physical Anhedonia
      Scale (PAS) and a physical sub-scale (FCPCS-PP) extracted from the Fawcett Clark
      pleasure scale. The severity of depression was rated using the Bech HDRS
      (Hamilton Depression Rating Scale) subscale for global severity. The results have
      shown that the major depressives are significantly more anhedonic than controls.
      The PAS mean score of depressives (m = 24.45, sd = 9.22) was significantly higher
      than the meaning score of normals (m = 16.9, sd = 7.13) (t = 4.7, df = 107, p =
      0.0001). The FCPCS-PP mean score of depressives (m = 81, sd = 15) was
      significantly lower than the mean score of normals (m = 90.6, sd = 7.3) (t = 4.2,
      df = 107, p = 0.0001). The Pearson correlation coefficients between the anhedonia
      scales (PAS and FCPCS-PP) and the Bech HDRS were not statistically significant.
      Anhedonia in major depression seems to be independent of the depression
      intensity. The distribution of the PAS and the FCPCS-PP scores have been studied
      in the major depressive group using a test of normality (chi 2 analysis). The
      results have shown for each scale a normal distribution. Our results do not
      support the hypothesis of the existence of a severely anhedonic sub-group of
      major depressives.

PMID- 8529566
TI  - [Activity and motivational disorders in neurology: proposal for an evaluation
      scale].
AB  - Isolated disturbances of motivation and action have recently been reported
      following focal (anoxic, toxic or ischemic) lesions of the basal ganglia. Their
      postulated mechanism is thought to involve bilateral dysfunction in a cortico
      subcortical loop centered on the limbic part of the striato-pallidum. Such
      disturbances also occur as a consequence of more diffuse brain damage, such as in
      vascular or degenerative dementias. Clinically, patients show dramatic decrease
      in spontaneous acts, whereas the same acts are correctly performed on external
      demand (so-called "loss of auto activation"). Moreover, they also demonstrate a
      special "loss of interest, affect and elan vital" which is relevant to both
      diagnosis and physiopathologic issues. Finally, they very often report a unique
      feature of decrease or absence of spontaneous thoughts, which is reversible upon
      external stimulation as well. In this article, the various clinical features of
      this syndrome are reviewed, based on the relevant literature as well as the
      author's personal experience. A new rating scale is proposed in order to evaluate
      specifically disorders of motivation and action in brain-damaged patients.

PMID- 8529567
TI  - [Prevalence of obsessive-compulsive disorders in a large French patient
      population in psychiatric consultation].
AB  - Recent epidemiologic studies were conducted in general population, showing high
      rate prevalence of obsessive-compulsive disorder (OCD) (2-3%). Although more
      investigation of OCD prevalence in clinical population is still warranted. The
      prevalence of DSM III-R diagnosis of OCD and obsessive-compulsive syndromes (OCS)
      is reported in 4 364, 16-70 year old new consecutive patients, consulting in out
      patient psychiatry. Point prevalence rates of 9.2% were recorded for OCD and 17%
      for OCS. Significantly different from non obsessional patients, it was observed
      in OCD and OCS patients more male representation (41% vs 37%, p = 0.007), a
      younger current age (36 y vs 39 y, p < 10(-4)) and age of disorder onset, higher
      rate of celibat (31.5% vs 28.6%) and lesser of separated or widowed (9.4% vs
      16.2%, p = 0.003), more anxiety and depression comorbidity (50% vs 39%, p < 10(
      4), a higher suicidal risk (17% vs 14%, p = 0.04--especially in OCS patients:
      18.3%), more chronicity (mean current episode duration: 14.8 months vs 11.2 m., p
      < 10(-4)) and higher rate of global functioning impairment (score at GAF: 53.9 vs
      57.9, p < 10(-4)). The results of the french survey confirmed the high prevalence
      of OCD and OCS in patients seeking psychiatric treatment. OCS (or subclinical
      OCD) seem to form a valid group (high rates of comorbidity and suicidal attempts)
      which need to be recognized and to receive adequate treatment.

PMID- 8529568
TI  - [Glutamatergic hypothesis of schizophrenia: psychoses induced by phencyclidine
      and cortical-subcortical imbalance].
AB  - Glutamatergic hypothesis stemmed from the observation of phencyclidine-induced
      psychosis. Phencyclidine is able to induce in healthy subjects negative and
      positive schizophrenic-like symptoms, as well as thought disorganization.
      Phencyclidine acts as an antagonist of NMDA receptor, one of the glutamatergic
      receptors. Experimental studies in animals have demonstrated that compartmental
      effect of phencyclidine is due to its action at striatal level, allowing the
      disinhibition of down-stream structures. The organization of the two striato
      thalamocortical loops, which exert, respectively, a positive and negative retro
      control on cortical activity, may explain how a glutamatergic deficiency induces
      both positive and negative symptoms. Positive symptoms could also be due to a
      secondary hyperdopaminergia, since a part of striatum, the striosomes, connected
      with limbic system, control the activity of dopaminergic neurons. This model
      validates the hypothesis that a single anomaly can lead to the different
      symptomatic dimensions of schizophrenia and supports the implication of basal
      ganglia in the expression of mental disease.

PMID- 8529569
TI  - [Parallel visual processing characteristics in healthy alexithymic subjects.
      Administration of the Toronto Alexithymia Scale and the parallel visual
      information test].
AB  - Alexithymia is a concept created by Sifneos and characterized by an inability to
      find words to describe feelings or emotions. The phenomenon seems to be also
      related to a poverty of cognitive and symbolic processes (de Bonis, 1986).
      Alexithymia was first studied in psychosomatic disorders, then in several other
      somatic disorders as chronic bronchitis, chronic pain, obesity, abuse disorders.
      It also appears in non medically ill subjects. The french validation of the
      Toronto alexithymia Scale (TAS) in general population (n = 786) has shown 8.14%
      alexithymia frequency. The TAS is a 26-items self-report measure rated on a five
      point likert scale. In the study we use the TAS and we refer to a visual test:
      the Parallel Visual Information Processing Test (PVIPT), involving the
      connexionist theory in the neuropsychological approach of alexithymia. The
      neuropsychological model is based on cerebral hemispheric specialization:
      emotions are localized in the right hemisphere and verbal expression depends on
      the left hemisphere in right-handed persons. The model posits that alexithymia is
      related to a lack of connection between the two cerebral hemispheres. It explains
      the deficit to verbally articulate emotions. The aim of our study is to compare
      the quality of cognitive and symbolic process (PVIPT) in alexithymic and non
      alexithymic subjects in general population. 773 students are tested with the TAS.
      We find 47 alexithymic subjects (6.08%). 22 alexithymic subjects and the control
      group (35 non alexithymic subjects) are evaluated with the PVIPT. Results are
      coherent with our previous studies on alexithymia in somatic disorders on one
      hand and alexithymia in neurological disease on the other hand. Theorical model,
      clinical observation and experimental results tend to define congruent hypothesis
      relative to the anxious pathology, supporting the reflexion and the research in
      the domain of the emotional disorders.

PMID- 8529570
TI  - [Cognitive experimental approach to anxiety disorders].
AB  - Cognitive psychology is proposing a functional model to explain the mental
      organisation leading to emotional disorders. Among these disorders, anxiety
      spectrum represents a domain in which this model seems to be interesting for an
      efficient and comprehensive approach of the pathology. Number of behavioral or
      cognitive psychotherapeutic methods are relating to these cognitive references,
      but the theorical concepts of cognitive "shemata" or cognitive "processes" evoked
      to describe mental functioning in anxiety need an experimental approach for a
      better rational understanding. Cognitive function as perception, attention or
      memory can be explored in this domaine in an efficient way, allowing a more
      precise study of each stage of information processing. The cognitive model
      proposed in the psychopathology of anxiety suggests that anxious subjects are
      characterized by biases in processing of emotionally valenced information. This
      hypothesis suggests functional interference in information processing in these
      subjects, leading to an anxious response to the most of different stimuli.
      Experimental approach permit to explore this hypothesis, using many tasks for
      testing different cognitive dysfunction evoked in the anxious cognitive
      organisation. Impairments revealed in anxiety disorders seem to result from
      specific biases in threat-related information processing, involving several
      stages of cognitive processes. Semantic interference, attentional bias, implicit
      memory bias and priming effect are the most often disorders observed in anxious
      pathology, like simple phobia, generalised anxiety, panic disorder or post
      traumatic stress disorder. These results suggest a top-down organisation of
      information processing in anxious subjects, who tend to detect, perceive and
      label many situations as threatening experience. The processes of reasoning and
      elaboration are consequently impaired in their adaptative function to threat,
      leading to the anxious response observed in clinical condition. The cognitive,
      behavioral and emotional components of this anxious reaction maintain the
      stressful experience for the subject, in which the self cognitive competence
      remain pathologically decreased. Cognitive psychology proposes an interesting
      model for the understanding of anxiety, in a domain in which subjectivity could
      benefit from an experimental approach.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8529571
TI  - [Psychotropic effects of angiotensin-converting enzyme inhibitors: what are the
      arguments?].
AB  - The authors report a case of acute mania induced by perindopril (Coversyl) in a
      57 year old man with no prior history of mental illness. This Angiotensin
      Converting Enzyme Inhibitor (ACEI) had been introduced eight days prior to the
      first signs of excitation, in order to treat recently diagnosed arterial
      hypertension. Without proof of reintroduction, and on the basis of clinical
      observations, the attribution appears plausible. Similar observations have been
      made for other molecules in this class of medication, such as captopril (Lopril).
      A review of literature regroups recent data concerning psychotropic effects of
      ACEIs. Several reports claim that captopril clearly acts as an antidepressant.
      Studies on the mood or the quality of life of treated hypertensive patients show
      ACEIs to have an euphoric-type positive effect compared to other anti
      hypertensive treatments. Captopril and perindopril also act like potential
      antidepressants in experimental models of antidepression. Furthermore,
      pharmacologic data confirm that the most lipophilic ACEIs penetrate the central
      nervous system and argue in favor of the role of these molecules in activating
      central opioides. As these data provide evidence of mood swing in some patients,
      but also of an overall benefit in hypertensive populations, the clinical
      importance of the antidepressant effect of ACEIs needs further investigations.

PMID- 8529572
TI  - Growth factors in breast cancer.

PMID- 8529573
TI  - Dynamin and endocytosis.

PMID- 8529574
TI  - Actions of placental and fetal adrenal steroid hormones in primate pregnancy.
AB  - It is clear that steroid hormones of placental and fetal adrenal origin have
      critically important roles in regulating key physiological events essential to
      the maintenance of pregnancy and development of the fetus for extrauterine life.
      Thus, progesterone has suppressive actions on lymphocyte proliferation and
      activity and on the immune system to prevent rejection of the developing fetus
      and placenta (see Fig. 9). Progesterone also suppresses the calcium-calmodulin
      MLCK system and thus activity of uterine smooth muscle, thereby promoting
      myometrial quiescence to ensure the maintenance of pregnancy. Estrogen enhances
      uteroplacental blood flow and possibly placental neovascularization to provide
      optimal gas exchange and the nutrients required for the rapidly developing fetus
      and placenta. In turn, estrogen has specific stimulatory effects on the receptor
      mediated uptake of LDL by, and P-450scc activity within, syncytiotrophoblasts,
      thus promoting the biosynthesis of progesterone. Moreover, there is an estrogen
      dependent developmental regulation of expression of the LDL receptor and NAD
      dependent 11 beta-HSD in the placenta, processes reflecting
      functional/biochemical differentiation of the trophoblast cells with advancing
      gestation. The increase in 11 beta-HSD causes a change in transplacental
      corticosteroid metabolism, which results in activation of the HPAA in the fetus.
      As a result of this cascade of events, there is an increase in expression of
      pituitary POMC/ACTH and key enzymes, e.g. 3 beta-HSD and P-450 17 alpha
      hydroxylase, important for de novo cortisol formation by, and consequently
      maturation of, the fetal adrenal gland. In turn, cortisol has well defined
      actions on surfactant biosynthesis and consequently fetal lung maturation, as
      well as effects on placental CRH/POMC release, which may be important to the
      initiation of labor. At midgestation, estrogen also selectively feeds back on the
      fetal adrenal to suppress DHA and maintain physiologically normal levels of
      estrogen. Preparation of the breast for lactation and nourishment of the newborn
      appears to involve a multifactorial system of regulation that includes estrogen.
      It is apparent, therefore, that autocrine/paracrine, as well as endocrine,
      systems of regulation are operative within the fetoplacental unit during primate
      pregnancy. A major goal of this review has been to illustrate the critically
      close functional communication existing between the developing placenta and fetus
      in the biosynthesis and the actions of steroid hormones during primate pregnancy.
      The functional interaction of the human fetal adrenal and placenta with respect
      to the biosynthesis of estrogen was demonstrated many years ago. However, the
      recent studies presented in this review show that the endocrine interaction
      between the fetus and placenta is more extensive, involving complex physiological
      regulatory mechanisms. Thus, as illustrated in Fig. 9, estrogen, acting via its
      receptor within the placenta and other reproductive tissues, orchestrates the
      dynamic interchange between the placenta and fetus responsible for the
      developmental regulation of the biosynthesis of the various steroid and peptide
      hormones and their receptors necessary for the maintenance of pregnancy and
      development of a live newborn. It would appear, therefore, that the immediate and
      long range challenges in this area of reproductive endocrinology are to employ in
      vitro molecular and in vivo experimental approaches simultaneously to elucidate
      the nature of these complex interactions and define the cellular and molecular
      mechanisms underlying these important regulatory events.

PMID- 8529575
TI  - Diacylglycerol production, Ca2+ influx, and protein kinase C activation in
      sustained cellular responses.

PMID- 8529576
TI  - Chemical safety: a global challenge.

PMID- 8529577
TI  - Are environmental sentinels signaling?
AB  - There is an increasing perception that environmental contamination by chemicals
      no longer poses a significant health threat and that relaxation of environmental
      regulations is warranted. However, many wildlife populations are showing signs of
      developmental, behavioral, and reproductive dysfunction due to environmental
      contamination by endocrine-disrupting chemicals. Scientists, regulators, and
      legislators must mobilize to identify current health threats posed by
      environmental pollutants, develop testing protocols that will detect such
      properties of new chemicals, and strengthen legislation designed to protect
      environmental health.

PMID- 8529578
TI  - New mouse is a knockout.

PMID- 8529579
TI  - More muddy water.

PMID- 8529580
TI  - Reviving hemp.

PMID- 8529582
TI  - EHPnet.

PMID- 8529581
TI  - Mother's milk.

PMID- 8529583
TI  - Mining the radon studies.

PMID- 8529584
TI  - Environmental health science in the city by the Bay.

PMID- 8529585
TI  - Sustaining health in the southern hemisphere.

PMID- 8529586
TI  - Northern exposures: cleaning up Canada.

PMID- 8529587
TI  - Can you keep a secret?

PMID- 8529588
TI  - A breath of fresh technology.

PMID- 8529590
TI  - Health effects in a casual sample of immigrants to Israel from areas contaminated
      by the Chernobyl explosion.
AB  - We analyzed questionnaire and physician examination data for 1560 new immigrants
      from the former USSR divided into three groups by potential exposure to Chernobyl
      radiation. Two groups were chosen according to soil contamination by cesium-137
      at former residences, as confirmed by our findings in a 137Cs body burden study.
      The third group consisted of "liquidators," persons who worked at the Chernobyl
      site after the disaster. Liquidators had greater self-reported incidences of
      symptoms commonly accepted as acute effects of radiation exposure, increases in
      prevalence of hypertension, and more health complaints. Excesses of bronchial
      asthma and health complaints were reported in children from the more exposed
      communities. Asthma prevalence in children potentially exposed in utero appears
      to be increased eightfold. Older adults from more exposed areas had more
      hypertension as assessed by history and measurements. These findings suggest the
      possible association of radiation exposure with several nonmalignant effects.

PMID- 8529591
TI  - Identifying chemical carcinogens and assessing potential risk in short-term
      bioassays using transgenic mouse models.
AB  - Cancer is a worldwide public health concern. Identifying carcinogens and limiting
      their exposure is one approach to the problem of reducing risk. Currently,
      epidemiology and rodent bioassays are the means by which putative human
      carcinogens are identified. Both methods have intrinsic limitations: they are
      slow and expensive processes with many uncertainties. The development of methods
      to modify specific genes in the mammalian genome has provided promising new tools
      for identifying carcinogens and characterizing risk. Transgenic mice may provide
      advantages in shortening the time required for bioassays and improving the
      accuracy of carcinogen identification; transgenic mice might now be included in
      the testing armamentarium without abandoning the two-year bioassay, the current
      standard. We show that mutagenic carcinogens can be identified with increased
      sensitivity and specificity using hemizygous p53 mice in which one allele of the
      p53 gene has been inactivated. Furthermore, the TG.AC transgenic model, carrying
      a v-Ha-ras construct, has developed papillomas and malignant tumors in response
      to a number of mutagenic and nonmutagenic carcinogens and tumor promoters, but
      not to noncarcinogens. We present a decision-tree approach that permits, at
      modest extra cost, the testing of more chemicals with improved ability to
      extrapolate from rodents to humans.

PMID- 8529589
TI  - Biokinetics of nuclear fuel compounds and biological effects of nonuniform
      radiation.
AB  - Environmental releases of insoluble nuclear fuel compounds may occur at nuclear
      power plants during normal operation, after nuclear power plant accidents, and as
      a consequence of nuclear weapons testing. For example, the Chernobyl fallout
      contained extensive amounts of pulverized nuclear fuel composed of uranium and
      its nonvolatile fission products. The effects of these highly radioactive
      particles, also called hot particles, on humans are not well known due to lack of
      reliable data on the extent of the exposure. However, the biokinetics and
      biological effects of nuclear fuel compounds have been investigated in a number
      of experimental studies using various cellular systems and laboratory animals. In
      this article, we review the biokinetic properties and effects of insoluble
      nuclear fuel compounds, with special reference to UO2, PuO2, and nonvolatile,
      long-lived beta-emitters Zr, Nb, Ru, and Ce. First, the data on hot particles,
      including sources, dosimetry, and human exposure are discussed. Second, the
      biokinetics of insoluble nuclear fuel compounds in the gastrointestinal tract and
      respiratory tract are reviewed. Finally, short- and long-term biological effects
      of nonuniform alpha- and beta-irradiation on the gastrointestinal tract, lungs,
      and skin are discussed.

PMID- 8529593
TI  - Special issue dedicated to Professor Stellan Hjerten.

PMID- 8529592
TI  - A longitudinal study of chronic lead exposure and physical growth in Boston
      children.
AB  - We investigated the cross-sectional and longitudinal relationships between
      chronic exposure to lead and physical growth among a cohort of children
      reassessed 13 years after initial examination. We measured weight, height, and
      dentin lead levels of 270 children in 1975-78. In 1989-1990 we reexamined 79 of
      these children for measurement of weight, height, and bone lead levels by means
      of in vivo K X-ray fluorescence. To avoid potential confounding by race and
      chelation history, analysis was restricted to white subjects without a history of
      lead chelation therapy. A total of 236 subjects provided complete information for
      the study of cross-sectional relationship between dentin lead levels and changes
      in physical growth: 58 subjects for the study of longitudinal relationship
      between dentin lead levels and changes in physical growth and 54 subjects for the
      study of longitudinal relationship between bone lead levels and changes in
      physical growth. Dentin lead levels averaged 14.9 micrograms/g; tibia and patella
      lead levels averaged 1.2 and 5.0 micrograms/g, respectively. With control for
      potential confounders including age, sex, baseline body size, and mother's
      socioeconomic status, log10 dentin lead level was positively associated with body
      mass index as of 1975-1978 (beta = 1.02, p = 0.03) and increase in body mass
      index between 1975-78 and 1989-90 (beta = 2.65, p = 0.03). Bone lead levels were
      not significantly associated with physical growth. This is the first study
      relating chronic lead exposure to body mass index. The results suggest that
      chronic lead exposure in childhood may result in obesity that persists into
      adulthood.

PMID- 8529594
TI  - New types of large-pore polyacrylamide-agarose mixed-bed matrices for DNA
      electrophoresis: pore size estimation from Ferguson plots of DNA fragments.
AB  - The average pore size value of gels containing polyacrylamide, covalently linked
      to agarose, was found to be 30% higher than the value of a regular N,N'
      methylenebisacrylamide (Bis) cross-linked gel of the same %T. By increasing the
      agarose concentration (10% of the total amount of polyacrylamide), gels
      containing low amounts of acrylamide (1.5-2%) are reproducibly obtained; their
      pore sizes are 130% larger than the pore sizes of a 4%T, 3.3%C polyacrylamide
      gel. In general, mixed-bed matrices were found to be more elastic and
      mechanically stronger than classical polyacrylamide gels since an agarose-induced
      gelation process takes place during their polymerization.

PMID- 8529595
TI  - A comparison of resolution of DNA fragments between agarose gel and capillary
      zone electrophoresis in agarose solutions.
AB  - The resolving power of capillary zone electrophoresis (CZE) is compared to that
      of gel electrophoresis (GE) under similar conditions (agarose, similar length of
      DNA fragments, identical buffer) but with differences in temperature and field
      strength. The comparison is based on the time required to reach a desired degree
      of resolution by each of the two methods. A resolution parameter is developed
      which is equally applicable to CZE, with relatively diffuse initial conditions in
      the absence of stacking and measurements expressed in terms of time, and to GE,
      in which measurements are expressed in terms of spatial parameters. The
      resolution time in CZE using agarose solutions at 40 degrees C was found to be
      greater by at least one order of magnitude than that in GE using agarose gels.
      Thus, the increased migration velocity due to high field strength in CZE
      substantially outweighs the lower dispersion in GE.

PMID- 8529596
TI  - Some reminiscences of the history of electrophoresis.
AB  - Dole's and Longsworth's solution of the whole set of moving boundary equations by
      using the dimensionless transference numbers is reviewed. Longsworth's teachings
      on the nature of transference numbers and his pondering over transference numbers
      of proteins led the author to inquire why transference numbers of ampholytes were
      never measured. Logical reasoning on this subject led to the invention of
      isoelectric focusing.

PMID- 8529597
TI  - Electrophopretic mobility of soft particles.
AB  - A recent theory of electrophoresis of "soft" particles, i.e., polyelectrolyte
      coated colloidal particles (Ohshima, J. Colloid Interface Sci. 1994, 163, 474
      483), is reviewed. This theory unites two different electrophoresis theories for
      rigid colloidal spherical particles and for spherical polyelectrolytes. An
      example is given of the analysis of electrophoretic mobility data on hydrogel
      layer-coated latex particles.

PMID- 8529598
TI  - Manipulation of a single cell with microcapillary tubing based on its
      electrophoretic mobility.
AB  - Manipulation of a single cell of spherical shape, approximately 5-10 microns in
      diameter, was performed with capillary tubing and an electrostatic field. A
      single cell migrates with its electrophoretic mobility into capillary tubing
      against the flow of electroosmosis coming out of the capillary. After trapping
      the cell in the capillary, it is pulled out into the other microreservoir with
      the application of a reverse electric voltage. When we apply a negative voltage
      to the microreservoir itself, the cell in it can keep floating for a relatively
      long period due to electrostatic repulsion. The electrophoretic mobility of a
      single cell is also estimated.

PMID- 8529599
TI  - A computer model for time-based simulation of electrophoresis systems with freely
      defined initial and boundary conditions.
AB  - A PC-based program has been developed that allows the user to perform one
      dimensional computer simulations of electrophoresis systems with freely definable
      initial- and boundary conditions. The program can handle n constituents with n pK
      values and calculates constituent concentrations and derived parameters as a
      function of time. Results are displayed graphically on screen and are stored as
      data files for graphical hard-copy processing.

PMID- 8529600
TI  - Calculation of the isoelectric points of native proteins with spreading of pKa
      values.
AB  - The isoelectric points (pI) of native proteins are important in several
      separation techniques. For estimating pI values the net charge of several
      proteins was calculated versus pH by use of the Henderson-Hasselbalch equation.
      Amino acid composition, pKa values for amino acid side chains and for the N- and
      C-terminal groups, and the presence of other charged groups were taken into
      account. A set of pKa values was chosen for amino acid residues with ionizable
      side chains. Each particular type of ionizable group was assumed to have pKa
      values distributed around the chosen value, thereby simulating the situation in
      proteins and polypeptides. The calculated pI values showed reasonably good
      agreement with experimental ones for most of 16 native proteins over a wide pH
      range (3.4-11) when charge contributions of heme groups, sialic acid residues,
      etc., were taken into account. The calculated pI for the human red cell glucose
      transporter (Glut1) with one sialic acid residue was decreased from 8.8 to 8.5 by
      introducing pKa value spreading and became consistent with the experimental pI
      value of 8.4 +/- 0.05 at 15 degrees C determined in the presence of 6 M urea. The
      pI of the native Glut1 was lower, 8.0 +/- 0.1, at 22 degrees C. In general, the
      pI values for native proteins are affected by the three-dimensional structure of
      the proteins, which causes greater differences between calculated and
      experimental pI values than in the case of polypeptides for which pI values are
      determined in the presence of urea.

PMID- 8529601
TI  - Characterization of proteins by sequential isoelectric focusing on immobilized pH
      gradients and electrospray mass spectrometry.
AB  - The coupling of isoelectric focusing on immobilized pH gradients (IPG) with
      electrospray-mass spectrometry (ES-MS) was applied to the characterization of
      proteins according to two different and important properties, such as net surface
      charge and molecular mass. From a technical point of view, these methods are
      complementary, since ES-MS requires ion-free samples as usually supplied by
      isoelectric focusing on IPGs. This report describes the experiments carried out
      on model proteins to demonstrate the feasibility of the sequential application of
      these two techniques for the characterization of proteins. A minimum of 5
      micrograms protein was needed for good signal by mass spectrometry. The following
      proteins were studied: myoglobin, truncated interleukin-6-mutein, recombinant
      cytochrome c551 and insulin-like growth factor I. Extraction from the IPG matrix
      was carried out in 70% acetonitrile/30% water/0.05% trifluoroacetic acid either
      by passive diffusion or by centrifugation through a 0.22 micron Amicon membrane,
      with protein recoveries of 80-85%.

PMID- 8529602
TI  - From image processing to classification: III. Matching patterns by shifting and
      stretching.
AB  - A method for the classification of electrophoretic patterns is described and
      tested on a data set representing ten wheat varieties. The method attempts to
      match each electropherogram to each variety by a transformation involving
      displacement and stretching along the x-axis. This is done essentially by the
      method of least squares, which uses only the information contained in the
      electropherogram itself to adjust it to the variety in question. The method is
      completely automatic and works extremely well by classifying 98% of the spectra
      correctly, judged by cross validation.

PMID- 8529603
TI  - Sensitive quantification of proteins by electrophoresis in gels by use of
      chemiluminescence.
AB  - For protein quantitation in gels or blotting membranes, chemiluminescence (CL)
      offers the advantages of a substantial improvement of detection limits. Easy-to
      use CL-chemicals and specific probes such as antibodies conjugated to enzymes,
      e.g. alkaline phosphatase (AP) may be used in combination with a newly developed
      luminometer. CL was found to have low detection limits and a linear relation
      between relative light units (RLU) and the concentration of the antibody enzyme
      complex present over a wide concentration range. Measurements of the
      immunoglobulin IgE in dot blots and in blots after sodium dodecyl sulfate (SDS)
      electrophoresis under nonreducing conditions in agarose gels are described.

PMID- 8529604
TI  - Electrophoretic size separation of proteins treated with sodium dodecyl sulfate
      in 1% agarose gels.
AB  - Separation of proteins treated with sodium dodecyl sulfate (SDS) according to
      molecular size was achieved by discontinuous electrophoresis in vertical low
      concentration agarose gels. A linear relationship was found between the migration
      distance and the square root of the molecular weight. This holds for proteins in
      the range of 7-200 kDa separated in 1.25% w/v agarose gel slabs (7 x 7 x 0.15 cm)
      with 0.1% w/v SDS and sulfate as leading ion. The linear regression coefficient
      was 0.998. The molecular weight and charge of coions influenced the separation.
      Small ions with low pKa values were found suitable as coions. The migration
      distance of proteins treated with SDS varied linearly with the agarose
      concentration of the gel. The agarose type and quality affected the resolution of
      the SDS-protein bands. We conclude that agarose gels can substitute
      polyacrylamide gels for the separation of proteins treated with SDS. A
      homogeneous agarose gel at a concentration of about 1% is a nonsieving support
      for electrophoresis. Therefore, the separation described here cannot be explained
      by the pore size of the gel. The results suggest that the separation is mainly
      due to the relative migration velocities of the coion and the proteins treated
      with SDS.

PMID- 8529605
TI  - Electrophoretic and chromatographic differentiation of two forms of albumin in
      equilibrium at neutral pH: new screening techniques for determination of ligand
      binding to albumin.
AB  - Analysis of normal human serum by crossed hydrophobic interaction
      immunoelectrophoresis with Phenyl-Sepharose revealed a biphasic appearance of the
      albumin peak. The molecular mechanism behind this apparent albumin heterogeneity
      was investigated. Analysis of defatted purified albumin showed that a major
      fraction bound to the Phenyl-Sepharose and that addition of ligands (e.g. long
      chain fatty acids, bilirubin, sulfonamides and warfarin) before electrophoresis
      blocked this binding to different degrees. A quantitative relation between ligand
      binding and the amount of nonbinding albumin was found. Thus the technique might
      be suitable for screening of ligand binding to albumin. Analysis of serum samples
      from newborns with hyperbilirubinemia revealed a positive correlation between the
      fraction of the nonretarded albumin and the bilirubin concentration. By
      chromatography on Phenyl-Sepharose, defatted albumin was separated into a binding
      and a nonbinding form and this technique was subsequently used to determine the
      kinetics of the intramolecular conversion. After rechromatography, each of the
      fractions could again be separated into two fractions, indicating the presence of
      an equilibrium. By varying the passage time for albumin on the column or varying
      the period between the first and the second separation it was possible to
      calculate the conversion rates. The half-life for the conversion was found to be
      as long as 1 1/4 h. It is the first time that a conformational change for albumin
      with such a long conversion time has been described experimentally.

PMID- 8529606
TI  - Detection of biotinylated proteins in crossed immunoelectrophoresis gels: studies
      on platelet membrane receptors and microparticles.
AB  - Biotinylation can be used as an alternative for surface labeling of cell membrane
      proteins. The use of the water soluble N-hydroxysulfosuccinimide (NHSS)-biotin or
      the more lipophilic N-hydroxysuccinimide (NHS)-biotin reagent has been
      investigated in the present study labeling two central receptor complexes on the
      platelet surface, i.e. the glycoprotein (GP) Ib-IX and the GP IIb-IIIa complexes
      involved in platelet adhesion and aggregation. Lack of labeling of the
      intracellularly located albumin was used as a negative control. The labeling has
      been studied using crossed immunoelectrophoresis in the PhastSystem format after
      extraction of the labeled cells in Triton X-100, and it is shown that, using
      enzyme-conjugated avidin and chromogenic substrates, the biotinylated proteins
      can be visualized directly in the dried electrophoresis gel without the need for
      a transfer to a blotting membrane as is used after sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Suitable conditions for biotinylation and for
      visualization in the crossed immunoelectrophoresis gels are described. Further,
      surface-biotinylation of platelets was used to observe shedding of microparticles
      as a consequence of formation of the complement membrane attack complex. For this
      purpose the formation and composition of the biotinylated microparticles were
      observed by flow cytometry and crossed immunoelectrophoresis.

PMID- 8529607
TI  - Micropreparative one- and two-dimensional electrophoresis: improvement with new
      photopolymerization systems.
AB  - To improve the efficiency of one- and two-dimensional electrophoresis for
      micropreparative purposes, the use of gels polymerized with other initiators than
      the standard N,N,N',N'-tetramethylethylenediamine (TEMED)/persulfate systems for
      sodium dodecyl sulfate electrophoresis has been investigated. We show here that
      the recently described photoinitiator system, composed of methylene blue, toluene
      sulfinate and diphenyliodonium chloride, leads to a decreased resolution.
      Resolution can be restored if methylene blue is replaced by riboflavin. Two
      dimensional electrophoresis with mg loadings of proteins has also been evaluated
      with these systems. Independently of the polymerization system, resolution for
      the first dimension is low with rod gels, increases with gel strips and is
      further improved when immobilized pH gradients are used. Here too, only the
      riboflavin/sulfinate/iodonium system results in a resolution that matches the one
      obtained with the standard TEMED/persulfate system. Gels polymerized with the
      riboflavin/sulfinate/iodonium system yield better results upon N-terminal
      microsequencing after blotting than gels polymerized with the standard
      TEMED/persulfate system.

PMID- 8529608
TI  - DNA separation with field inversion capillary electrophoresis.
AB  - We have built an automated pulsed field capillary electrophoresis system on the
      basis of a commercially available device. Using entangled polymer solutions as
      separating matrix, we demonstrate a considerable improvement of separation of
      double-stranded DNA in the range of 1-50 kbp under pulsed field conditions. The
      influence of the main parameters, i.e. pulse frequency and electric field, is
      studied and the results are compared to existing electrophoresis theories.

PMID- 8529609
TI  - Single strand conformational polymorphism using capillary electrophoresis with
      two-dye laser-induced fluorescence detection.
AB  - Capillary electrophoresis (CE), using a replaceable polymer matrix and two-dye
      laser-induced fluorescence has been applied to single strand conformational
      polymorphism (SSCP). Two-dye laser-induced fluorescence has been used for
      improved strand identification over a single-dye approach. Conditions suitable in
      the capillary format for rapid separation and high resolution have been explored.
      The influence of separation parameters such as temperature and matrix composition
      on separation in SSCP was first determined. Short analysis times allowed for fast
      screening of optimal separation conditions of the sample. Based on these results,
      the two strands of a standard 255 bp fragment of the lacI gene were resolved
      within 25 min with replaceable linear polyacrylamide as a separation matrix. The
      method was then applied to the detection of different mutations, in the presence
      of wild type, of a 276 bp fragment of the insulin-like growth factor 1-binding
      protein 1 (IGF1-BP3) gene.

PMID- 8529610
TI  - Rapid typing of variable number of tandem repeat locus in the human
      apolipoprotein B gene for DNA diagnosis of heart disease by polymerase chain
      reaction and capillary electrophoresis.
AB  - The apolipoprotein B (apoB) variable number of tandem repeat (VNTR) alleles
      containing larger repeat units is a risk factor for coronary heart disease.
      Capillary electrophoresis (CE) in entangled polymer solution was applied to the
      analysis of polymerase chain reaction (PCR) amplified apoB VNTR locus for DNA
      diagnosis of heart disease. The CE separation gives an excellent resolution of
      two alleles differing by one or two 16 bp repeat units in the DNA size range up
      to 600 bp with high speed. The apoB alleles differing in length by 2 or 4 repeat
      units are readily distinguishable by CE in the DNA size range from 600 to 1000
      bp. The plate number achieved was 1 million plates per meter. CE combining with
      PCR provides an excellent technique for accurate determination of the number of
      repeat units of apoB VNTR alleles and differentiation of heterozygous from
      homozygous individuals. Using the CE technique, the apoB VNTR loci from some
      individuals in genotyping were examined towards precise DNA diagnosis for
      coronary heart disease.

PMID- 8529611
TI  - Influence of electrolyte composition on the effective electric field strength in
      capillary zone electrophoresis.
AB  - In capillary zone electrophoresis the electrophoretic velocity of an ion
      decreases as the concentration of the background electrolyte solution is
      increased. This is caused by changes in the electrophoretic mobility of the ion
      (muep) as well as by changes in the net force affecting it, namely the effective
      electric field strength (Eeff). The electrophoretic mobility of an ion is altered
      through changes in absolute viscosity of the electrolyte solution and changes in
      the solvated size of the ion. Eeff is altered mainly by changes in the magnitude
      of the charge asymmetry effect and the electrophoretic effect, both of which
      retard the motion of ions. In this study, the three-marker technique was used to
      study the effect of background electrolyte concentration (0.02-0.08M 3
      [cyclohexylamino]-1-propanesulfonic acid and counter ion (Li, Na, K, and Cs) on
      Eeff. It was found that the concentration of the background electrolyte markedly
      affects Eeff and that Eeff approaches E as the concentration of the background
      electrolyte approaches zero. The counter ion had a minor effect on Eeff: as the
      size of the hydrated radius of the counter ion increased, Eeff decreased. The
      three-marker technique proved to be efficient for such determinations.

PMID- 8529612
TI  - Probing the inner surface of a capillary with the atomic force microscope.
AB  - The inner surface of a fused silica capillary for zone electrophoresis was probed
      by the atomic force microscope (AFM) in the contact mode. Only uncoated surfaces
      were analyzed, after a simple washing cycle with detergent, NaOH and HCl, and
      final equilibration in distilled water. Three progressively larger surface areas
      were probed: 0.5 x 0.5 micron, 2 x 2 microns and 4 x 4 microns. In all cases, it
      was found that the surface is remarkably smooth, with a median height increasing
      from 1.3 to 5.6 nm; mean height, from 1.3 to 5.8 nm; root-mean-squared roughness,
      from 0.35 to 1.5 nm; and average roughness, from 0.28 to 0.67 nm (the lower
      values referring to the smaller area, the larger to the largest area probed). The
      lowest "peaks" detected are of the order of 1-2 nm; some scattered peaks as high
      as 16 nm are occasionally found. It is concluded that the inner surface of a
      capillary is not a serrate or notchy structure, but is indeed quite smooth. Since
      the average roughness is comprised within the thickness of the diffuse double
      layer (> 10 nm) existing on the silica wall as a result of silanol ionization
      (and, in fact, it is on the average considerably smaller), it is concluded that
      it cannot possibly influence peak shape and contribute to peak decay in an
      electrophoretic run.

PMID- 8529613
TI  - Chemical stability of polyacrylamide-coating on fused silica capillary.
AB  - The chemical stability of polyacrylamide coatings on a fused silica capillary for
      capillary electrophoresis was investigated with respect to temperature of
      capillary and pH as well as salt concentration of running buffer solution by
      evaluating their effects on electroosmotic mobility. The capillary covalently
      bonded to linear polyacrylamide through Si-C linkage was stable in buffer
      solutions of pH 2.3-8.0 at 30 degrees C for 30 days, whereas the capillary bonded
      through Si-O-Si-C linkage was damaged at pH above 4.6. The electroosmotic
      mobility observed in both capillaries increased with increasing temperature,
      though the degree of increase was smaller in the Si-C linked capillary than in
      the Si-O-Si-C linked capillary. The increase in the buffer concentration resulted
      in increased electroosmotic mobility in the Si-O-Si-C linked capillary, but no
      effect was observed for the Si-C linked capillary.

PMID- 8529614
TI  - Effect of organic modifier concentrations on electrokinetic migrations in
      micellar electrokinetic chromatography.
AB  - The effect of low concentrations of organic modifiers on the electroosmotic
      mobility, mueo, and electrophoretic mobility of the micelle, muep, mc, in
      micellar electrokinetic chromatography (MEKC) with sodium dodecyl sulfate (SDS)
      solutions was investigated. The results showed that mueo was mainly influenced by
      the viscosity of the running solution. A linear relationship between mueo and the
      concentration of the organic modifier was found in MEKC. A newly defined
      parameter, the mobility ratio, Rm, mc, which is the ratio of the electrophoretic
      mobility of the micelle to the electroosmotic mobility, and which characterizes
      the surface charge density of the micelle in MEKC system with organic modifiers,
      was introduced. A linear relationship between Rm, mc and the organic modifier
      concentration was observed. The parameter Rm, mc was found to be useful to
      investigate the changes in the micellar phase with the addition of organic
      modifier. The measured muep, mc values showed different and interesting
      characteristics among different organic modifiers.

PMID- 8529616
TI  - Sodium dodecyl sulfate-gel electrophoresis of proteins employing short
      capillaries.
AB  - The performance of capillary gel-sodium dodecyl sulfate (SDS) electrophoresis for
      molecular-mass-dependent separation of proteins has been examined employing cross
      linked polyacrylamide gels and untreated fused-silica capillaries of short
      length. An apparatus for capillary electrophoresis has been constructed,
      combining a UV detector equipped with a capillary holder, a power supply, and a
      micromanipulator for sample loading. The apparatus is capable of accommodating
      gel capillaries of different lengths and can be operated with two methods of
      sample loading: manual injection on top of the gel or electrokinetic injection.
      Standard proteins have been separated according to their molecular mass (ranging
      from 17000 to 116000) within 30 min, employing gel capillaries of effective
      lengths shorter than 10 cm and polyacrylamide gels ranging from 2.4 to 4.8%T
      (5%C). The results confirmed that gel capillaries of effective length less than
      10 cm can be used for protein size-separation by SDS electrophoresis, with much
      higher performance than is achieved in rod gel-SDS electrophoresis.

PMID- 8529615
TI  - A new mode of size-dependent separation of proteins by capillary electrophoresis
      in presence of sodium dodecyl sulfate and concentrated oligomeric dextran.
AB  - Capillary electrophoresis in presence of sodium dodecyl sulfate (SDS) and 10% w/v
      of oligomeric dextran with molecular weight of just above 1000 was found to be an
      efficient medium for size-dependent separation of proteins (Karim, M. R., Janson,
      J.-C., Takagi, T., Electrophoresis 1994, 15, 1531-1534). The separations were
      found to be highly reproducible, both with respect to the position and relative
      amounts of the peaks. No evidence for a network structure in the medium could be
      found on examination of the effect of dextran concentration and viscosity
      measurements. The separation mechanism appears to be different from sieving by a
      polymer network structure. In free solution, SDS-protein complexes with molecular
      weights > 10,000 migrate with almost the same mobilities, irrespective of their
      molecular weight (this behavior is called free draining). Such SDS-complexes of
      proteins or peptides with molecular weights < 10,000, however, tend to increase
      their negatively signed mobilities with decreasing molecular weight (Karim, M.
      R., Shinagawa, S., Takagi, T., Electrophoresis 1994, 15, 1141-1146). Our working
      hypothesis is that in presence of the oligomeric dextran, the range of deviation
      from the free-draining electrophoretic behavior extends to higher molecular
      weights, resulting in a novel separation made.

PMID- 8529617
TI  - Fluorescence imaging detection for capillary isoelectric focusing.
AB  - A simple laser-induced fluorescence (LIF) imaging detector and an ultrasensitive
      LIF imaging detector are described for capillary isoelectric focusing (CIEF). An
      argon ion laser beam of 496.5 nm is used as excitation source. In the simple LIF
      imaging detector, the excitation beam is directed into a capillary column by an
      optic fiber array. In the ultrasensitive LIF imaging detector, the laser beam is
      first expanded, then is focused into the 4.5 cm long capillary column by a
      cylindrical lens. Fluorescence emission is detected by a charge-coupled device
      (CCD) camera. The feasibility and performance of the LIF imaging detector system
      for CIEF are first verified with a naturally fluorescent protein, b
      phycoerythrin. Then, the ultrasensitive LIF imaging system is used as a detector
      for CIEF of proteins labeled with fluorescein isothiocyanate (FITC). Three FITC
      labeled proteins (i) alpha-D-galatosylated FITC-albumin, (ii) insulin-FITC, and
      (iii) casein-FITC, are used as model samples. Fluorescence images of the model
      samples are measured during the CIEF process. The focusing of the protein samples
      is complete in about 1.5 min. The ultrasensitive detector's detection limits for
      the FITC-labeled proteins are at the level of 10(-10) M, and the mass detection
      limits are about 4.5 x 10(-17) mole, even though only 10% of the fluorescence
      emission is collected. Therefore, the method is capable of separating and
      detecting 10(-11) M or amole (10(-18) mole) level protein samples with a band
      pass filter more specific to the fluorescence light.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8529618
TI  - Fluorescence-labeled peptides as isoelectric point (pI) markers in capillary
      isoelectric focusing with fluorescence detection.
AB  - Commercially available peptides, mostly angiotensin derivatives, were labeled at
      their N-terminal amino group with 5-carboxytetramethylrhodamine succinimidyl
      ester, to obtain fluorescent pI markers for capillary isoelectric focusing with
      fluorescence detection. The labeled peptides were purified by reversed-phase
      chromatography. They were well separated on isoelectric focusing in a
      polyacrylamide gel slab and their pIs were determined by comigration with protein
      pI markers. The fluorescent markers could be detected as sharp peaks in capillary
      isoelectric focusing with laser-induced fluorescence detection (He-Ne laser, 1
      mW, 543.5 nm). The detection limit was found to be around 3 x 10(-12) M (0.8
      amol). Tetramethylrhodamine-labeled pea lectin (3 pg) was subjected to capillary
      isoelectric focusing and the pIs of the fluorescent derivatives of the lectin
      were determined by using the fluorescence-labeled peptides as pI markers.

PMID- 8529619
TI  - Screening of umbilical cord blood hemoglobins by isoelectric focusing in
      capillaries.
AB  - Separation and quantitation of the three main hemoglobin components of umbilical
      cord blood (fetal, acetylated fetal and adult hemoglobins; Hb F, Fac, A) by
      capillary isoelectric focusing (IEF) in a pH 6-8 gradient is reported. Even in
      coated capillaries (with covalently bound chains of linear acrylamido
      derivatives, notably N-acryloylaminoethoxyethanol), no base line separation is
      obtained between Hb F and A, although this is routinely achieved in gel slab IEF.
      However, when the carrier ampholyte buffers were added to 3% short-chain liquid
      linear polyacrylamide, base line resolution and stabilization of peak transit
      times were obtained. This suggests that even in the best coating procedures,
      patches of the inner capillary surface could still be naked, so that the static
      coating is complemented by a dynamic coating on the unoccupied sites. An
      additional improvement in separation occurs if the above mixture, comprising 5%
      carrier ampholytes in the pH 6-8 range and 3% soluble polyacrylamide, is made to
      contain 50 mM beta-alanine, a "separator" known to flatten the pH gradient around
      pH 7. In the normal newborns analyzed (n = 30), the following average values were
      obtained: Hb F, 70.1% (range 65-75%); Hb A, 20.2% (range 15-25%); and HbFac, 9.5%
      (range 7-11%).

PMID- 8529620
TI  - The use of capillary electrophoresis for the determination of hemoglobin
      variants.
AB  - The application of capillary electrophoresis and related techniques for the
      detection of hemoglobin variants is described. Capillary zone electrophoresis
      (CZE) was applied for the analysis of intact tetrameric hemoglobin. CZE under
      denaturing conditions was used for the separation of globin chains. Both CZE and
      micellar electrokinetic capillary chromatography were applied for a fast and
      sensitive separation of tryptic digests and for the analysis of amino acid
      derivatives.

PMID- 8529621
TI  - Capillary electrophoresis of carboxylated carbohydrates. Part 2. Selective
      precolumn derivatization of sialooligosaccharides derived from gangliosides with
      7-aminonaphthalene-1,3-disulfonic acid fluorescing tag.
AB  - The most suitable conditions for selective precolumn derivatization of
      sialooligosaccharides, derived from gangliosides, with 7-aminonaphthalene-1,3
      disulfonic acid (ANDSA) and the subsequent separation of the derivatives by
      capillary electrophoresis are described. ANDSA-sialooligosaccharide derivatives,
      which fluoresce at 420 nm when excited at 315 nm, were readily detected in
      capillary electrophoresis using an on-column lamp-operated fluorescence detector.
      In addition, the precolumn derivatization described here, which exploited the
      reactivity of the carboxylic acid group of the sialic acid residue of the
      oligosaccharides, replaced each weak carboxylic acid group of the parent sugar by
      two strong sulfonic acid groups. This allowed for electrophoresis over a wide
      range of pH and improved the resolution of the derivatives when compared to those
      obtained with underivatized sialooligosaccharides under identical separation
      conditions. The separation of sialooligosaccharides was best achieved when 75 mM
      borate, pH 10.0, was used as the running electrolyte. The derivatization and
      separation conditions described herein are expected to be readily transposed to
      the capillary electrophoresis of other sialooligosaccharides such as those
      derived from glycoproteins.

PMID- 8529622
TI  - Further study on the use of uncharged beta-cyclodextrin polymer in capillary
      electrophoresis: enantiomeric separation of some alpha-hydroxy acids.
AB  - Uncharged beta-cyclodextrin polymer was used as chiral selector for the
      enantiomeric separation of some alpha-hydroxy acids by capillary electrophoresis.
      Complexation and enantiomeric resolution of mandelic acid, m-hydroxy and p
      hydroxymandelic acid, 3,4-dihydroxymandelic acid, as well as 2- and 3
      phenyllactic acid were studied, changing the concentration of the beta
      cyclodextrin polymer added to the background electrolyte at different pH in the
      range of 4.5-7. Furthermore, the effects of the concentration of the background
      electrolyte, column temperature, and applied voltage on chiral resolution were
      also examined. The best enantiomeric separations were obtained using a background
      electrolyte at pH 6 containing 100 mg/mL of beta-cyclodextrin polymer.

PMID- 8529623
TI  - Separation of tryptophan-derivative enantiomers with iron-free human serum
      transferrin by capillary zone electrophoresis.
AB  - Enantiomers can be separated by using human serum transferrin as a chiral phase.
      With the help of the native protein we were able to separate enantiomers with
      high efficiency, using a low ionic strength 2-(N-morpholino)ethanesulfonic acid
      (MES) buffer, pH 6, in capillary zone electrophoresis. Tryptophan methyl, ethyl
      and butyl ester enantiomers-moving towards the cathode at pH 6-were resolved by
      passing through an iron-free transferrin zone in coated capillaries. Since the
      isoelectric point of the iron-free transferrin is a little higher than 6, the
      protein zone is either not moving in the experiment or is slowly moving towards
      the anode. Under the simplest experimental conditions the highest resolution was
      obtained for the butyl ester enantiomers and the lowest for the methyl ester
      ones. By changing the experimental conditions, however, this order could be
      reversed. The results indicate that the lengths of the alkyl chains in the
      enantiomers have a significant effect on the resolution, i.e., on the interaction
      between the protein and the separands.

PMID- 8529624
TI  - Liposome capillary electrophoresis for analysis of interactions between lipid
      bilayers and solutes.
AB  - Liposomes, which mimic biomembranes, were used as a pseudostationary phase in
      capillary zone electrophoresis. The decrease in the mobility of an analyte owing
      to the presence of liposomes reflected interaction between the analyte and the
      liposomes. Equations were derived to calculate the specific capacity factor Ks
      (the capacity factor, k', normalized to the liposome concentration 1 M) from the
      migration times and to estimate the difference in free energy, delta(delta G0),
      of the weak analyte/liposome interactions. The order of Ks values for the drugs
      tested was aspirin < salicylic acid < warfarin << sulfasalazine. The peptide
      TyrGlySerThrProGlyCysCys interacted more strongly with the liposomes (Ks = 10.1 M
      1) than did TyrGlySerThrProGlySerSer (Ks = 9.1 M-1). These results were similar
      to those obtained earlier by immobilized liposome chromatography.

PMID- 8529625
TI  - Coelectrophoresis of cardiac tissue from human, dog, rat and mouse: towards the
      establishment of an integrated two-dimensional protein database.
AB  - We have investigated the feasibility of identifying homologous proteins in whole
      tissue protein extracts of dog, mouse and rat hearts by comparison with our human
      heart two-dimensional (2-D) database. Samples of ventricular myocardial tissue
      from each of these species were coelectrophoresed with a human tissue sample.
      Gels were silver stained and patterns were analysed using PDQUEST. The number of
      proteins comigrating with human proteins was 301, 201 and 356 for the dog, mouse
      and rat, respectively. In the dog pattern, 33 of these comigrating proteins were
      tentatively identified from the similarity between their migration properties and
      those of known human proteins. Twenty-nine such proteins were identified in the
      mouse pattern while 30 comigrating rat proteins were identified. While these
      tentative identifications require confirmation, we feel that this technique
      offers a useful shortcut in the characterisation of proteins present in similar
      tissue samples from different species and avoids the necessity for duplicating
      laborious procedures, such as protein microsequencing, otherwise used in the
      identification of these proteins in each species.

PMID- 8529626
TI  - Differential expression of nucleophosmin and stathmin in human T lymphoblastic
      cell lines, CCRF-CEM and JURKAT analyzed by two-dimensional gel electrophoresis.
AB  - Two-dimensional gel electrophoresis was used to study the expression of
      intracellular proteins in adherent cells of human T lymphoblastic cell line, CCRF
      CEM. The adherent cells grown in monolayer on a culture plate decreased the
      amount of proteins of M(r) 37,000 and pI 4.7-4.9, and of 17,000 and pI 5.7. The
      proteins were identified to be nucleophosmin for the 37,000 protein and stathmin
      for the 17,000 protein by microsequencing their CNBr fragments. The amount of
      proteins was increased in CCRF-CEM cells grown in floating mass to a comparable
      level of JURKAT cells which grew in floating mass throughout the culture. The
      adherent cells decreased their growth rate as compared with the cells in the
      floating mass. These results suggest that the adhesion of human T lymphoblastic
      cells modulates their morphology and proliferation via a concomitant decrease in
      the amount of nucleophosmin and stathmin.

PMID- 8529627
TI  - Identification of two sites in gelsolin with different sensitivities to adenine
      nucleotides.
AB  - The affinity of monomeric actin for several actin-binding proteins, including
      gelsolin, depends on adenine nucleotides. Gelsolin binds faster and with higher
      affinity to ADP-actin than to ATP-actin. Here, we show that the C-terminal actin
      binding domain of gelsolin, which is required for filament nucleating activity
      but not for filament severing activity, contains the site that distinguishes
      between ATP-actin and ADP-actin monomers. In contrast, actin binding to the N
      terminal half of gelsolin depends on solution ATP concentrations, but not on the
      nucleotide (ATP or ADP) tightly bound in the cleft of the actin monomer. Binding
      is stronger in the absence of free nucleotide or in the presence of 0.5 mM ADP
      than in solutions containing 0.5 mM ATP. Complexes formed using different
      nucleotide concentrations differ in their filament-severing activities as well as
      in their abilities to increase the fluorescence of 4-chloro-7-nitrobenzeno-2-oxa
      1,3-diazole-labeled actin monomers. These results suggest that, at physiologic
      concentrations of nucleotides, both free and actin-bound ATP may affect the
      binding of actin to its accessory proteins and that gelsolin, actin, or the
      gelsolin-actin complex, contains a low-affinity nucleotide-binding site.

PMID- 8529628
TI  - Different human interleukin-4 mutants preferentially activate human or murine
      common receptor gamma chain.
AB  - Interleukin-4 (IL-4) shows species-specific activity due to species-restricted
      interaction with the IL-4 receptor alpha (IL-4R alpha) chain. The second subunit
      of a functional IL-4 receptor, the common gamma chain (gamma c), is more
      promiscuous, since human IL-4 is able to activate IL-4 receptor complexes
      containing either human or murine common gamma receptor chain (gamma c). We have
      stably transfected factor-dependent mouse cells of myeloid and lymphoid origin
      with combinations of human IL-4R alpha and gamma c derivatives. In these cell
      lines, both human and murine gamma c receptors as well as IL-4R alpha chains from
      both species are simultaneously expressed. Both versions of gamma c readily form
      ternary complexes with either human IL-4 and human IL-4R alpha or murine IL-4 and
      murine IL-4R alpha. Due to distinct ligand-binding properties of human and murine
      gamma c, the two receptor complexes can be activated preferentially by different
      mutant variants of human IL-4. The contribution of murine common gamma chain to
      human IL-4-induced signal transduction is suppressed by an inhibitory antibody
      directed to the extracellular domain of the mouse gamma c. We present evidence
      that the two IL-4R complexes functionally interfere with each other and compete
      for response-limiting signalling components.

PMID- 8529629
TI  - Isoproterenol inhibits insulin-stimulated tyrosine phosphorylation of the insulin
      receptor without increasing its serine/threonine phosphorylation.
AB  - The effect of a beta-adrenergic agonist (isoproterenol) on the tyrosine kinase
      activity of the insulin receptor was studied in intact adipocytes. Isoproterenol
      treatment rapidly (5 min) inhibited the insulin-induced autophosphorylation of
      the insulin receptor on tyrosine residues in intact adipocytes. The effect of
      insulin on the phosphorylation of cellular proteins on tyrosine residues was also
      inhibited by isoproterenol. In order to understand the mechanism responsible for
      this inhibition, two-dimensional phosphopeptide mapping of the insulin receptor
      was performed. The pattern of phosphorylation of the insulin receptor in freshly
      isolated adipocytes showed marked differences from that previously observed in
      cultured cells overexpressing insulin receptors. These differences include a
      larger proportion of receptors being phosphorylated on the three tyrosines from
      the kinase domain and no apparent phosphorylation of the two tyrosines close to
      the C-terminus after insulin stimulation. Isoproterenol markedly inhibited the
      effect of insulin on the phosphorylation of the three tyrosines from the kinase
      domain. However, this inhibition was not associated with an increase in the
      phosphorylation of serine/threonine peptides. Thus, this direct analysis of
      insulin receptor phosphorylation sites in intact adipocytes does no support the
      idea that beta-adrenegic agents inhibit the tyrosine kinase activity of the
      receptor through a serine/threonine phosphorylation-dependent mechanism.

PMID- 8529630
TI  - Structure and expression analysis of the gdcsPA and gdcsPB genes encoding two P
      isoproteins of the glycine-cleavage system from Flaveria pringlei.
AB  - In Flaveria pringlei, a C3 plant, P protein of the glycine-cleavage system is
      encoded by a small gene family consisting of at least five transcriptionally
      active genes. We have cloned and sequenced two of these genes, gdcsPA and gdcsPB,
      and provide the first detailed report on the complete structure of eukaryotic
      gdcsP genes. Based on the lengths of exons and intervening sequences, the P
      protein genes can be subdivided into two parts. In both cases the N-terminal
      region consists of one very long exon followed by a long intron. In contrast, the
      C-terminal parts show a complex mosaic structure of relatively small exons and
      introns. A highly conserved leucine-zipper motif was identified, which is
      supposed to participate in the assembly of the glycine decarboxylase multienzyme
      complex. The transcript derived from the gdcsPA sequence corresponds perfectly to
      a leaf cDNA isolated earlier. Reverse-transcriptase PCR experiments show that
      both genes are preferentially active in leaves. Stems contain distinctly less P
      protein mRNA and the relative level in roots is very low but still clearly
      detectable. In all three organs, but most significantly in roots, the gdcsPA
      transcript level is distinctly higher than that of gdcsPB. Analysis of promoter
      beta-glucuronidase fusions in transgenic tobacco suggests that far-upstream
      elements enhance the transcriptional activity of both genes in leaves relative to
      stems. The analysis of distal gdcsPA promoter deletions reveals the presence of
      regulatory elements acting with a distinct organ preference and indicates their
      approximate location.

PMID- 8529631
TI  - Immunohistochemical and biochemical analyses of 20,000-25,000-year-old fossil
      cartilage.
AB  - A cracked, irregular pellicle adhering to fossilized bone excavated from the
      Enlene cave (Ariege) and estimated to date from 20,000-25,000 years BP was
      examined to verify its cartilaginous nature, suggested previously on the basis of
      optical and electron microscopic investigations. Immunolabeling of the organic
      component revealed the presence of type II and IX collagens, associated with
      residual glycosaminoglycans, in the external zone of the pellicle. The
      cartilaginous nature of the pellicle was also demonstrated by biochemical
      identification of type II collagen as the major protein in the demineralized
      sample: the amino acid compositions of insoluble and soluble fractions were
      similar to that of pure type II collagen; cyanogen-bromide-generated peptides,
      prepared after reduction of the sample, had an electrophoretic pattern similar to
      that of cyanogen bromide peptides derived from type II collagen. The amino acid
      sequences of four tryptic peptides were identical to the corresponding human type
      II sequences. It was impossible to isolate intact alpha chains. All of the
      solubilized fractions were composed of a wide range of low-molecular-mass
      peptides demonstrating significant degradation of the collagen molecules that was
      not reflected in the well-preserved fibrillar structure observed at the
      ultrastructural level. The mineral fraction, characterized by X-ray diffraction,
      consisted of apatite (as in sub-chondral bone) associated with contaminating
      poorly crystallized components originating from the cave sediment. Energy
      dispersive spectrometry showed that the cartilaginous zone contained three times
      less phosphorus and calcium than the underlying bone. These results confirm the
      cartilaginous nature of the sample and the preservation of tissue-specific
      components, and suggest that the process of fossilization is closely related to a
      mechanism of phosphatization.

PMID- 8529632
TI  - Properties of isolated domains of the elongation factor Tu from Thermus
      thermophilus HB8.
AB  - The relative contributions of the three domains of elongation factor Tu (EF-Tu)
      to the factor's function and thermal stability were established by dissecting the
      domains apart with recombination techniques. Domain I (EF-TuI), domains I/II (EF
      TuI/II) and domain III (EF-TuIII) of the EF-Tu from Thermus thermophilus HB8
      comprising the amino acids 1-211, 1-312 and 317-405, respectively, were
      overproduced in Escherichia coli and purified. A polypeptide consisting of domain
      II and III (EF-TuII/III) was prepared by limited proteolysis of native EF-Tu with
      V8 protease from Staphylococcus aureus [Peter, M. E., Reiser, C. O. A., Schirmer,
      N. K., Kiefhaber, T., Ott, G., Grillenbeck, N. W. & Sprinzl, M. (1990) Nucleic
      Acids Res. 18, 6889-6893]. As determined by circular dichroism spectrometry, the
      isolated domains have the secondary structure elements found in the native EF-Tu.
      GTP and GDP binding as well as GTPase activity are maintained by the EF-TuI and
      EF-TuI/II; however, the rate of GDP dissociation from EF-TuI . GDP and EF-TuI/II
      . GDP complex is increased as compared to native EF-Tu . GDP, reflecting a
      constraint imposed by domain III on the ability to release the nucleotide from
      its binding pocket located in domain I. A weak interaction of Tyr-tRNATyr with
      the EF-TuI . GTP suggests that domain I provides a part of the structure
      interacting with aminoacyl-tRNA. The domain III is capable of regulating the rate
      of GTPase in EF-Tu, since the polypeptide consisting only of domains I/II has a
      39-fold higher intrinsic GTPase compared to the native EF-Tu. No in vitro poly(U)
      dependent poly(Phe) synthesis was detectable with a mixture of equimolar amounts
      of domains I/II and domain III, demonstrating the necessity of covalent linkage
      between the domains of EF-Tu for polypeptide synthesis. In contrast to native EF
      Tu and EF-TuII/III, EF-TuI and, to a lesser extent the polypeptide consisting of
      domains I/II, are unstable at elevated temperatures. This indicates that domains
      II/III strongly contribute to the thermal stability of this T. thermophilus EF
      Tu. Deletion of amino acid residues 181-190 from domain I of T. thermophilus EF
      Tu decreases the thermostability to that of EF-Tu from E. coli, which does not
      have these residues. Interdomain interactions must be important for the
      stabilisation of the structure of domain I, since isolated T. thermophilus EF-TuI
      is thermolabile despite the presence of the 181-190 loop.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8529634
TI  - Sequential 1H and 15N nuclear magnetic resonance assignments and secondary
      structure of the lipoyl domain of the 2-oxoglutarate dehydrogenase complex from
      Azotobacter vinelandii. Evidence for high structural similarity with the lipoyl
      domain of the pyruvate dehydrogenase complex.
AB  - A 79-amino-acid polypeptide, corresponding to the lipoyl domain of the
      succinyltransferase component of the 2-oxoglutarate dehydrogenase multienzyme
      complex from Azotobacter vinelandii, has been sub-cloned and produced in
      Escherichia coli. Complete sequential 1H and 15N resonance assignments for the
      lipoyl domain have been obtained by using homo- and hetero-nuclear NMR
      spectroscopy. Two antiparallel beta-sheets of four strands each were identified
      from characteristic NOE connectivities and 3JHN alpha values. The lipoyl-lysine
      residue is found in a type-I turn connecting two beta-strands. The secondary
      structure of the lipoyl domain very much resembles the secondary solution
      structure of the N-terminal lipoyl domain of the A. vinelandii pyruvate
      dehydrogenase complex, despite the sequence identity of 25%. A detailed
      comparison of the NMR-derived parameters of both lipoyl domains, i.e. chemical
      shifts, NH-exchange rates, NOEs, and 3JHN alpha values suggests a high structural
      similarity in solution between the two lipoyl domains. Preliminary tertiary
      structure calculations confirm that these lipoyl domains have very similar
      overall folds. The observed specificity of the 2-oxo acid dehydrogenase
      components of both complexes for these lipoyl domains is discussed in this
      respect.

PMID- 8529633
TI  - Functional consequences of the Ser334-->Pro mutation in a human factor X variant
      (factor XMarseille).
AB  - A factor X molecular variant was identified in a 55-year-old woman at a routine
      preoperative coagulation screening. Plasma factor X antigen was normal, whereas
      factor X activity was decreased when factor X was activated by either the
      extrinsic pathway (21%), the intrinsic pathway (21%) or the factor X activator
      from Russell viper venom, RVV-X (26%). Factor XMarseille was isolated from plasma
      by immunoaffinity chromatography and compared with normal factor X purified by
      the same method. Activation of factor XMarseille by factor IXa or by RVV-X in a
      purified system showed that the rate of cleavage was decreased, whereas once
      produced, factor XaMarseille had a normal catalytic efficiency for either the
      peptide substrate S-2765 (D-Arg-Gly-Arg-NH-Np) or prothrombin. The rate of
      inhibition of factor XaMarseille by antithrombin III was also normal. Defective
      proteolysis of factor XMarseille by factor IXa or by RVV-X was the consequence of
      a threefold decrease in the kcat for the activation of factor XMarseille while
      the Km of RVV-X or factor IXa for factor X was normal. We have determined the
      molecular basis of the defect in the factor XMarseille gene by amplification of
      all eight exons, single-strand conformational polymorphism analysis of the
      amplified exons and subsequent sequence analysis. The patient was homozygous for
      a T-->C mutation in exon VIII, resulting in the substitution of Ser334 by
      proline. From comparison of three-dimensional models of various serine proteases,
      it appears that Ser334 is located within a surface-exposed variable region of
      factor X. This observation suggests that the Ser334-->Pro mutation either is
      responsible for a misalignment of the active sites of specific factor X
      activators in close proximity to the cleavage site, or that the Ser-->Pro
      mutation alters the spatial orientation of the cleavage site by nonlocal
      modifications of factor X structure.

PMID- 8529635
TI  - Impaired photosystem II in a mutant of Chlamydomonas reinhardtii defective in
      sulfoquinovosyl diacylglycerol.
AB  - The photosynthetic apparatus was characterized in a mutant of Chlamydomonas
      reinhardtii, hf-2, defective in the synthesis of a chloroplast-specific lipid,
      sulfoquinovosyl diacylglycerol (SQui-acyl2Gro). hf-2 showed reduced photosystem
      II (PSII) activity with little effect on photosystem I (PSI) activity, as
      compared with the parent. PAGE in the presence of dodecyl beta-D-maltoside
      (DodGlc2) of C. reinhardtii thylakoid membranes was used to isolate chlorophyll
      protein complexes without chlorophyll (Chl) release in order to examine lipid
      species bound to these complexes. The four complexes obtained were shown to be
      the PSI complex, the PSII core complex and the two groups of the light-harvesting
      complex of PSII by analyses of 77-K emission spectra of Chl fluorescence and of
      subunit compositions. Lipid analysis of Chl-protein complexes in the parent
      revealed the localization of SQui-acyl2Gro in the PSII core complex and the two
      groups of the light-harvesting complex of PSII, but not in the PSI complex. These
      results suggest that SQui-acyl2Gro is responsible for PSII activity by
      associating with the core and light-harvesting complexes of PSII.

PMID- 8529636
TI  - Reversible dissociation and unfolding of dimeric creatine kinase isoenzyme MM in
      guanidine hydrochloride and urea.
AB  - The unfolding of dimeric cytoplasmic creatine kinase (MM) by guanidine
      hydrochloride and by urea has been investigated using activity measurements, far
      ultraviolet circular dichroism, sedimentation velocity and fluorescence energy
      transfer experiments to monitor global structural changes. Intrinsic (cysteine
      and tryptophan residues) and extrinsic probes (1-anilinonaphthalene-8-sulfonate)
      were also used. The reversibility of the unfolding was checked by monitoring
      activity and tryptophan fluorescence. The unfolding of creatine kinase in
      guanidine hydrochloride is a reversible multistep process, as suggested by the
      non-coincidence of denaturation curves at equilibrium. Inactivation of the dimer
      precedes its dissociation into two monomers and an intermediate state was
      identified during the unfolding of the monomer. This intermediate state is
      characterized by a relatively high degree of secondary structure (as shown by far
      ultraviolet circular dichroism), of compactness (as shown by fluorescence energy
      transfer measurements and sedimentation experiments), a fluctuating tertiary
      structure (as shown by near-ultraviolet circular dichroism) and a strong affinity
      for anilinonaphthalene sulfonate (as demonstrated by fluorescence). These results
      clearly indicate that the intermediate state detected possesses some of the
      properties of a molten globule. In urea, the unfolding pathway is reversible but
      differs from that observed in guanidine hydrochloride. Indeed inactivation,
      dissociation and loss of tertiary structure are coincident but the ellipticity
      curve is slightly shifted to a higher urea concentration. The dimer is
      dissociated into two expanded monomers possessing some secondary structure which
      is progressively lost at a higher urea concentration (6.4M). These results show
      that guanidine hydrochloride is approximately six times more effective than urea
      for inactivation and dissociation, underlining the fact that electrostatic
      interactions are very important in the stabilization of the active site and of
      the dimeric state.

PMID- 8529637
TI  - Identification of a three-amino-acid region in G protein gamma 1 as a determinant
      of selective beta gamma heterodimerization.
AB  - Guanine-nucleotide-binding protein beta and gamma subunits belong to large
      protein families encompassing at least five and ten members, respectively, from
      mammalian cells. The formation of stable beta gamma heterodimers is a selective
      process determined by the primary sequences of both the beta and gamma subunit.
      For example, gamma 2 dimerizes with both beta 1 and beta 2, gamma 1 with beta 1,
      but not with beta 2. To identify the structural elements of gamma subunits
      relevant to the selectivity of beta gamma dimerization, we have used the
      baculovirus-insect cell-expression system to produce chimeric beta and gamma
      subunits and have studied their dimerization using an assay based on the ability
      of isoprenylation-resistant gamma subunit mutants to draw beta subunits into the
      cytosol and including sucrose density gradient analysis of soluble recombinant
      beta gamma dimers. The results show that replacement of three consecutive
      residues of gamma 1, Cys36-Cys37-Glu38, by the corresponding residues of gamma 2,
      Ala33-Ala34-Ala35, suffices to render the mutant gamma 1 subunit capable of
      forming heterodimers with beta 2. The ability of mutant gamma 1 subunits to
      dimerize with beta 2 does not correlate with the probability of the mutated
      region to participate in coiled-coil structures. The tripeptide region identified
      here as a critical determinant of the selectivity of beta gamma dimer formation
      is distinct from, but partially overlaps with, the region reported by Lee et al.
      [Lee, C., Murakami, T. & Simonds, W. F. (1995) J. Biol. Chem. 270, 8779-8784].
      The results of this study, therefore, not only extend the region of gamma 1
      selecting between beta 1 and beta 2 to the five-residue sequence between Cys36
      and Phe40, but also argue against the notion that the hydrophobic terminal
      residue of this motif represents the key determinant of selective beta gamma
      interaction.

PMID- 8529638
TI  - The affinity of human erythrocyte porphobilinogen synthase for Zn2+ and Pb2+.
AB  - Porphobilinogen synthase activity has been measured in human erythrocyte lysates
      supplemented with metal-ion buffers to control free Zn2+ and Pb2+ concentrations.
      The enzyme is activated by Zn2+ with a Km of 1.6 pM and inhibited by Pb2+ with a
      Ki of 0.07 pM. Pb2+ and Zn2+ appear to compete for a single metal-binding site.
      The half-time for loss of Zn2+ from the active site, or replacement of Pb2+ by
      Zn2+, were in the 10-20-min range at 37 degrees C. Zn2+ did not affect the
      affinity for the substrate 5-aminolevulinate, but Pb2+ reduced it non
      competitively. All the experiments were conducted with a blood sample of the
      common 1-1 phenotype [Astrin, K. H., Bishop, D. F., Wetmur, J. G., Kaul, B.,
      Davidow, B. & Desnick, R. J. (1987) Ann. NY Acad. Sci. 514, 23-29].

PMID- 8529639
TI  - Purification and characterization of protein PB of betaine reductase and its
      relationship to the corresponding proteins glycine reductase and sarcosine
      reductase from Eubacterium acidaminophilum.
AB  - Simple complementation assay systems were developed for the substrate-specific
      proteins PB of glycine reductase, sarcosine reductase, and betaine reductase, in
      which acetyl phosphate was detected as the product in all three cases. The
      betaine-specific subunits of protein B (PB betaine) responsible for betaine
      reductase activity were purified to homogeneity from cells of Eubacterium
      acidaminophilum. The molecular masses of the two different subunits were 45 kDa
      and 48 kDa according to SDS/PAGE. The molecular mass of the native protein was
      about 200 kDa, indicating and alpha 2 beta 2 structure. The glycine-specific
      protein B (PB glycine) was partially purified and subunits of 47 kDa and 27 kDa
      were N-terminally sequenced. The latter subunits cross-reacted with antibodies
      raised against PB betaine and showed high sequence similarity to the 45-kDa and
      48-kDa subunits of PB betaine, respectively. [2-14C]Glycine could be covalently
      coupled to the 47-kDa subunit by treatment with borohydride. By the same
      procedure, [2-14C]sarcosine labeled a protein of the same size. Like the
      sarcosine reductase activity, this protein was not present in glycine-grown
      cells, indicating its specific involvement in sarcosine metabolism. The labile
      viologen-dependent formate dehydrogenase purified with the respective PB proteins
      and could be tentatively assigned to a 95-kDa protein.

PMID- 8529640
TI  - Glycine reductase of Clostridium litorale. Cloning, sequencing, and molecular
      analysis of the grdAB operon that contains two in-frame TGA codons for selenium
      incorporation.
AB  - A 2.8-kb HindIII fragment, containing three open reading frames, has been cloned
      and sequenced from Clostridium litorale. The first gene grdA encoded the
      selenocysteine-containing protein PA of the glycine reductase complex, a protein
      of 159 amino acids with a deduced molecular mass of 16.7 kDa. The second gene
      (grdB) encoded the 47-kDa subunit of the substrate-specific selenoprotein PB
      glycine that is composed of 437 amino acids. The third gene contained the 5'
      region of the gene for thioredoxin reductase, trxB. All gene products shared high
      similarity with the corresponding proteins from Eubacterium acidaminophilum. In
      both genes grdA and grdB, the opal termination codon (TGA) was found inframe,
      indicating the presence of selenocysteine in both polypeptides. Northern-blot
      analysis showed that grdA and grdB are organized as one operon. Unlike
      Escherichia coli, no stable secondary structures of the corresponding mRNA were
      found immediately downstream of the UGA codons to direct an insertion of
      selenocysteine into the grdA and grdB transcripts of C. litorale. Instead, a
      secondary structure was identified in the 3'-untranslated region of grdB.

PMID- 8529641
TI  - A novel serine/threonine-specific protein phosphotransferase activity of
      Nm23/nucleoside-diphosphate kinase.
AB  - Two human nm23 genes have been identified, designated nm23-H1 and nm23-H2, which
      encode the 88% identical nucleoside-diphosphate kinase (NDPK) A and NDPK B
      polypeptides, respectively. The nm23-H1 gene product has been shown to play a
      functional role in the suppression of tumor metastasis. The Nm23 proteins/NDPK
      are highly conserved throughout evolution and are implicated in controlling
      cellular differentiation and development in various species, while the underlying
      mechanisms remain undefined. Neither the NDPK activity nor the DNA-binding
      activity, identified recently for NDPK B, can satisfactory explain the regulatory
      functions of Nm23. The present study provides evidence that purified Nm23
      proteins are capable of transferring a phosphate group to other proteins when non
      denaturing amounts of urea are present. This novel Nm23/NDPK activity was found
      to be specific for serine and threonine residues, and the transphosphorylation of
      substrate proteins occurred stoichiometrically. Because of the absence of a
      substrate turn-over, the novel function was termed protein phosphotransferase
      activity instead of protein kinase activity. It is demonstrated that urea
      stimulates the interaction of NDPK with other proteins. Identical phosphoprotein
      patterns were obtained using purified NDPK preparations from human, Drosophila,
      yeast and Dictyostelium in the presence of urea. Partially purified NDPK from
      human erythrocytes produced a similar phosphorylation pattern independent of urea
      addition and also acted stoichiometrically. In this preparation, a protein
      phosphotransferase activity of Nm23 species may possibly be generated and/or
      stabilized by the interaction with copurified proteins. Using different mutants
      of Dictyostelium NDPK it was shown that the protein phosphotransferase activity
      depends on the same active site as the NDPK activity. A phosphotransfer mechanism
      analogous to that of protein-histidine kinases is proposed, involving a high
      energy phosphohistidine intermediate. Furthermore, the novel Nm23 function is
      compared with an apparently similar protein phosphotransferase activity which was
      observed previously with partially purified NDPK from different plant species.

PMID- 8529642
TI  - Characterization of neutrophil NADPH oxidase activity reconstituted in a cell
      free assay using specific monoclonal antibodies raised against cytochrome b558.
AB  - The immunochemical characterization of NADPH oxidase activity of cytochrome b558
      purified from human neutrophils was determined after reconstitution in a cell
      free assay using the native hemoprotein and recombinant purified cytosolic
      activating factors. The oxidase activity showed a strict dependence on the heme
      content at each step of the hemoprotein purification process. The immunochemical
      properties of the reconstituted oxidase made use of monoclonal antibodies raised
      against membrane-bound and octyl-glucoside-extracted cytochrome b. From nine
      specific monoclonal antibodies reacting with gp91-phox cytochrome b558, two were
      selected, both of which were found to bind to the beta subunit of cytochrome b558
      and to inhibit superoxide formation in the oxidase reconstituted cell-free assay.
      The extent of inhibition was dependent on the phospholipid environment.
      Neutrophil membrane extracts from X-linked chronic granulomatous disease patients
      did not produce O2- in the reconstituted system and did not bind to the
      antibodies.

PMID- 8529643
TI  - Tissue distribution and intracellular localisation of the 75-kDa inositol
      polyphosphate 5-phosphatase.
AB  - The 75-kDa inositol polyphosphate 5-phosphatase (75-kDa 5-phosphatase) hydrolyses
      several important mediators of intracellular calcium homeostasis, including
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], inositol 1,3,4,5-tetrakisphosphate
      [Ins(1,3,4,5)P4] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2].
      Northern analysis of various human tissues revealed the 75-kDa 5-phosphatase has
      a ubiquitous expression, where differential splicing may occur in specific
      tissues. Prominent expression of a 4.4-kb transcript was noted in human lung,
      thymus, testes and placenta, and a 4.6-kb transcript was observed in heart,
      brain, kidney, ovary and colon. Determination of the intracellular location of
      the enzyme by indirect immunofluorescence, demonstrated that the 75-kDa 5
      phosphatase was associated with mitochondrial and cytosolic cellular
      compartments. Immunoprecipitation of the total cell homogenate of human lung
      carcinoma cells (A549) with anti-(recombinant 75-kDa 5-phosphatase) antibodies
      revealed that the 75-kDa 5-phosphatase is the major PtdIns(4,5)P2 5-phosphatase
      in this cell line. Analysis of PtdIns(4,5)P2 5-phosphatase activity in
      subcellular fractions of A549 cells revealed peak 75-kDa 5-phosphatase enzyme
      activity in the cytosolic and mitochondrial enriched fractions. Immunoblot
      analysis further confirmed the mitochondrial location of the enzyme. This study
      demonstrates the tissue distribution and intracellular location of the 75-kDa 5
      phosphatase and reveals a novel location for an enzyme involved in
      phosphatidylinositol turnover.

PMID- 8529645
TI  - Peroxynitrite formed by simultaneous nitric oxide and superoxide generation
      causes cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation.
AB  - Nitric oxide reacts rapidly with superoxide to form the potent oxidant
      peroxynitrite. Mitochondria in vivo produce superoxide and in pathological
      situations the amount of superoxide produced increases; therefore, in the
      presence of nitric oxide, mitochondria will be a major site of peroxynitrite
      formation. Oxidative stress induces cyclosporin-A-sensitive mitochondrial calcium
      efflux and depolarisation which may contribute to tissue damage in pathological
      situations. To determine whether peroxynitrite could induce calcium efflux and
      depolarisation we exposed mitochondria to both nitric oxide and superoxide
      simultaneously, thus subjecting the mitochondria to a continual flux of
      peroxynitrite similar to that found in pathological situations. Our results show
      that: (a) exposure of mitochondria to nitric oxide plus superoxide induces
      cyclosporin-A-sensitive mitochondrial calcium efflux and depolarisation; (b)
      neither nitric oxide nor superoxide on their own induce calcium efflux or
      depolarisation under these conditions; (c) calcium efflux and depolarisation
      occur when peroxynitrite production (from nitric oxide and superoxide) exceeds
      about 0.99 +/- 0.03 nmol peroxynitrite.min-1 mg mitochondrial protein-1. This
      rate of production of peroxynitrite is similar in magnitude to superoxide
      formation by mitochondria in pathological situations, suggesting that
      mitochondria can produce sufficient peroxynitrite in vivo to cause mitochondrial
      calcium efflux and depolarisation. Our experiments suggest a plausible model for
      tissue damage when mitochondrial superoxide production increases, for example in
      ischaemia-reperfusion injury or following exposure to neurotoxins. In the
      presence of nitric oxide the mitochondrial superoxide production will lead to
      peroxynitrite formation which induces cyclosporin-A-sensitive mitochondrial
      calcium efflux and depolarisation. This disruption to mitochondrial function may
      in turn contribute to cell damage and death.

PMID- 8529646
TI  - Cartography of ribosomal proteins of the 30S subunit from the halophilic
      Haloarcula marismortui and complete sequence analysis of protein HS26.
AB  - By two-dimensional polyacrylamide gel electrophoresis of 30S ribosomal subunit
      proteins (S proteins) from Haloarcula marismortui we identified 27 distinct spots
      and analyzed all of them by protein sequence analysis. We demonstrated that
      protein HmaS2 (HS2) is encoded by the open reading frame orfMSG and has sequence
      similarities to the S2 ribosomal protein family. The proteins HmaS5 and HmaS14
      were identified as spots HS7 and HS21/HS22, respectively. Protein HS4 was
      characterized by amino-terminal sequence analysis. The spot HS25 was recognized
      as an individual protein and also characterized by sequence analysis.
      Furthermore, the complete primary sequence of HS26 is reported, showing
      similarity only to eukaryotic ribosomal proteins. The sequence data of a further
      basic protein shows a high degree of similarity to ribosomal protein S12,
      therefore, it was designated HmaS12. Slightly different results compared to
      published sequence data were obtained for the protein HS12 and HmaS19. The
      putative 'ribosomal' protein HSH could not be localized in the two-dimensional
      pattern of the total 30S ribosomal subunit proteins of H. marismortui. Therefore,
      it seems to be unlikely that this protein is a real constituent of the H.
      marismortui ribosome.

PMID- 8529644
TI  - The purification and properties of phosphonoacetate hydrolase, a novel carbon
      phosphorus bond-cleavage enzyme from Pseudomonas fluorescens 23F.
AB  - A novel, inducible, carbon-phosphorus bond-cleavage enzyme, phosphonoacetate
      hydrolase, was purified from cells of Pseudomonas fluorescens 23F grown on
      phosphonoacetate. The native enzyme had a molecular mass of approximately 80 kDa
      and, upon SDS/PAGE, yielded a homogenous protein band with an apparent molecular
      mass of about 38 kDa. Activity of purified phosphonoacetate hydrolase was Zn2+
      dependent and showed pH and temperature optima of approximately 7.8 and 37
      degrees C, respectively. The purified enzyme had an apparent Km of 1.25 mM for
      its sole substrate phosphonoacetate, and was inhibited by the structural
      analogues 3-phosphonopropionate and phosphonoformate. The NH2-terminal sequence
      of the first 19 amino acids displayed no significant similarity to other databank
      sequences.

PMID- 8529647
TI  - Evidence for ADP-ribosylation-factor-mediated activation of phospholipase D by m3
      muscarinic acetylcholine receptor.
AB  - Activation of phospholipase D (PLD) is a cellular response to a wide variety of
      extracellular ligands. However, the exact mechanisms that link cell surface
      receptors to PLD remain unclear. In this study, we report the involvement of the
      small-molecular-mass guanine-nucleotide-binding protein, ADP-ribosylation factor
      (ARF), in the activation of PLD by the muscarinic acetylcholine receptor (mAChR)
      in human embryonic kidney cells stably expressing the human m3 subtype. PLD
      stimulation in permeabilized cells by guanosine 5'-O-[gamma-thio]triphosphate
      (GTP[S]) was dependent on a cytosolic factor and reconstituted by purified
      recombinant ARF 1. Brefeldin A, a known inhibitor of the ARF guanine-nucleotide
      exchange-factor activity in Golgi membranes, inhibited mAChR-stimulated PLD,
      whereas basal PLD activity and stimulation by GTP[S] were not affected. Upon cell
      permeabilization without the addition of stimulus, ARF proteins were released.
      However, the addition of GTP[S] during permeabilization and mAChR activation
      before permeabilization caused an almost complete and partial (about 60%)
      inhibition, respectively, of ARF release, indicating that ARF proteins are
      activated and thereby translocated to membranes. The results indicate that ARF
      proteins and their nucleotide-exchange factor are apparently involved in the
      signalling pathway leading from mAChR activation to PLD stimulation in human
      embryonic kidney cells.

PMID- 8529648
TI  - Monoclonal antibodies against two electron reduced riboflavin and a
      quantification of affinity constants for this oxygen-sensitive molecule.
AB  - In order to create a protein environment that binds preferentially to the two
      electron reduced form of flavin, monoclonal antibodies have been raised against a
      reduced flavin derivative. Due to the low fluorescence quantum yield and visible
      light absorption and to the instability of reduced flavin in an aerobic
      environment, it is not possible to determine the affinities of these antibodies
      for two-electron-reduced flavin using standard techniques. Because of its
      sensitivity, time-resolved fluorescence can be used to overcome this problem.
      This technique has been applied to study the binding of two antibodies, an IgG1
      and an IgM, to reduced riboflavin (1,5-dihydroriboflavin) and oxidized riboflavin
      (riboflavin). The affinity of the IgG1 is more than 80 times larger for 1,5
      dihydroriboflavin than for riboflavin. From analysis of the dynamical parameters
      of the system it is apparent that the internal motion of 1,5-dihydroriboflavin
      bound to IgG1 is much more restricted than that of riboflavin. In contrast, the
      affinity of the IgM is only slightly higher for 1,5-dihydroriboflavin than for
      riboflavin and the flexibility of binding of both flavin redox states in the
      antigen binding site is almost similar.

PMID- 8529649
TI  - Isolation of the endothelin B receptor from bovine lung. Structure, signal
      sequence, and binding site.
AB  - Bovine lung endothelin-B receptor has been isolated in good yield with a new
      procedure involving the use of endothelin-1 coupled to iminobiotin with a long
      spacer and avidin-agarose affinity chromatography. Contrary to previous reports,
      evidence has been obtained that the native form of this receptor corresponds to
      the full-length transcript expected on the basis of cDNA clones. The binding of
      endothelin to a variety of shortened fragments of the full receptor suggests that
      the long N-terminal sequence of this receptor has very little influence on the
      binding of endothelin and that the main determinants of the endothelin binding
      site might be constituted by residues in the sixth, and possibly the seventh,
      transmembrane helices.

PMID- 8529650
TI  - Purification and characterization of a galactose-1-phosphate: UDP-glucose
      uridyltransferase from the red alga Galdieria sulphuraria.
AB  - The galactose-1-phosphate uridyltransferase of the red alga Galdieria sulphuraria
      has been purified about 1800-fold to a final specific activity of approximately
      140 U/mg protein. The purification involved chromatography on DEAE-Fractogel,
      hydroxyapatite, decyl-agarose, and DEAE-Tentacle gel. After SDS/PAGE, the enzyme
      preparation showed only one protein band of 42 kDa. The enzyme is a homodimer
      with a molecular mass of 82 kDa as estimated from the sedimentation velocity or
      60 kDa as estimated by gel filtration. It has a broad pH optimum between pH 7 and
      pH 9. The apparent Km values for the forward and backward reactions are Km(Glc1P)
      = 105 microM, Km(UDP-galactose) = 30 microM, Km(Gal1P) = 400 microM, and Km(UDP
      Glc) = 20 microM. The activation energy of the reaction is 45 kJ mol-1. The
      enzyme is specific for the galactose 1-phosphate to UDP-galactose interconversion
      in the Leloir pathway while the alternate enzyme for the Isselbacher pathway, UDP
      galactose pyrophosphorylase, could not be detected in G. sulphuraria.

PMID- 8529651
TI  - Prostaglandin-E2 9-reductase from corpus luteum of pseudopregnant rabbit is a
      member of the aldo-keto reductase superfamily featuring 20 alpha-hydroxysteroid
      dehydrogenase activity.
AB  - The prostaglandin-E2 9-reductase (PGE2 9-reductase) activity in the corpus luteum
      of rabbits corresponds to a cytosolic, NADPH-dependent enzyme with a molecular
      mass of 36 kDa. This enzyme was purified from corpora lutea on day 12 of
      pseudopregnancy with a 266-fold enrichment. The main purification step was
      affinity chromatography using Red Sepharose CL-6B. The efficiency of this column
      was improved by elution with 1 mM NADH prior to elution of the active fractions
      with 1 mM NADPH. Amino acid sequence data demonstrate that the rabbit luteal PGE2
      9-reductase has to be classified as a member of the aldo-keto reductase
      superfamily. The enzyme revealed a wide substrate specificity comprising the
      reduction of aldehydes, ketones, and quinones. Apparent kinetic constants were
      determined using methylglyoxal, DL-glyceraldehyde, and 9,10-phenanthrenquinone as
      substrates. The fully purified enzyme showed two catalytic activities of
      particular interest: PGE2 9-reductase and 20 alpha-hydroxysteroid dehydrogenase
      (20 alpha-HSD) activities. The competitive inhibition of 20 alpha-HSD activity by
      PGE2 indicates that progesterone and PGE2 are substrates for the same enzyme.
      From these results, we conclude that prostaglandin and steroid metabolism are
      tightly linked to each other. For this reason the aldo-keto reductase could be a
      key enzyme in the cascade of events leading to the regression of the corpus
      luteum in the rabbit.

PMID- 8529652
TI  - Substrate specificity of flavin-dependent vanillyl-alcohol oxidase from
      Penicillium simplicissimum. Evidence for the production of 4-hydroxycinnamyl
      alcohols from 4-allylphenols.
AB  - The substrate specificity of the flavoprotein vanillyl-alcohol oxidase from
      Penicillium simplicissimum was investigated. Vanillyl-alcohol oxidase catalyzes
      besides the oxidation of 4-hydroxybenzyl alcohols, the oxidative deamination of 4
      hydroxybenzylamines and the oxidative demethylation of 4-(methoxymethyl)phenols.
      During the conversion of vanillylamine to vanillin, a transient intermediate,
      most probably vanillylimine, is observed. Vanillyl-alcohol oxidase weakly
      interacts with 4-hydroxyphenylglycols and a series of catecholamines. These
      compounds are converted to the corresponding ketones. Both enantiomers of
      (nor)epinephrine are substrates for vanillyl-alcohol oxidase, but the R isomer is
      preferred. Vanillyl-alcohol oxidase is most active with chavicol and eugenol.
      These 4-allylphenols are converted to coumaryl alcohol and coniferyl alcohol,
      respectively. Isotopic labeling experiments show that the oxygen atom inserted at
      the C gamma atom of the side chain is derived from water. The 4-hydroxycinnamyl
      alcohol products and the substrate analog isoeugenol are competitive inhibitors
      of vanillyl alcohol oxidation. The binding of isoeugenol to the oxidized enzyme
      perturbs the optical spectrum of protein-bound FAD. pH-dependent binding studies
      suggest that vanillyl-alcohol oxidase preferentially binds the phenolate form of
      isoeugenol (pKa < 6, 25 degrees C). From this and the high pH optimum for
      turnover, a hydride transfer mechanism involving a p-quinone methide intermediate
      is proposed for the vanillyl-alcohol-oxidase-catalyzed conversion of 4
      allylphenols.

PMID- 8529653
TI  - Kinetic and stereochemical studies of manno-oligosaccharide hydrolysis catalysed
      by beta-mannanases from Trichoderma reesei.
AB  - The two beta-mannanases from Trichoderma reesei with pI of 4.6 and 5.4,
      respectively, have been characterised by NMR spectroscopy. Following the kinetics
      of manno-oligosaccharide degradation with complete progress-curve analysis the
      stereospecificity and degradation pattern have been delineated. It was found that
      degradation of mannotriose and mannopentaose proceeds with retention of the
      anomeric configuration. Mannotriose degradation proceeds by almost random release
      of mannose. For mannopentaose there is initially no mannose formed showing that
      only the two middle mannosidic linkages are attacked. Progress-curve analysis
      shows that there is preference (70%) for cleavage of mannopentaose in such a way
      that mannobiose is released from the reducing end. The final product composition
      from the mannotriose degradation showed that transglycosylation has to be taken
      into account. Model calculation and progress-curve analysis showed that the
      transglycosylation rate is the fastest of all the rates in this system, 15 s-1
      compared with mannohexaose and mannotetraose hydrolysis rates of 2 s-1 and
      mannotriose hydrolysis rate of 0.03 s-1 at 50 degrees C.

PMID- 8529654
TI  - Characterization of a cDNA encoding a cytosolic peptidylprolyl cis-trans
      isomerase from Blattella germanica.
AB  - Cyclophilins are an abundant and ubiquitous class of proteins first identified by
      their high affinity for the immunosuppressive drug cyclosporin A. Cyclophilins
      have peptidylprolyl cis/trans-isomerase activity in vitro, and thus may be
      involved in protein folding and trafficking in vivo. In this study, we report the
      cloning and characterization of a Blattella germanica cyclophilin cDNA. Analysis
      of this 846-bp cDNA reveals an open reading frame coding for a polypeptide of 164
      amino acid residues with a molecular mass of 17934 Da. This B. germanica
      cyclophilin shares a central peptidylprolyl cis/trans-isomerase and a cyclosporin
      A-binding domain with other cyclophilin sequences. The B. germanica cyclophilin
      amino acid sequence shares 83% identity with the cytosolic cyclophilin isoform
      from Drosophila melanogaster (Cyp-1). This identity suggests that B. germanica
      cyclophilin is a member of the cytosolic cyclophilin A (CyPA) family. From the
      alignment of cyclophilin sequences, we have found that 62 residues (positional
      identity of 40%) have remained invariant in eukaryotes for more than 1 billion
      years of divergence. We calculated a unit evolutionary period of 30.9 million
      years for the cytosolic isoform. Northern-blot analyses show that B. germanica
      CyPA mRNA is abundant, and present in all insect organs tested. The highest
      values for B. germanica cyclophilin mRNA tissue content were found in 6-day-old
      ovary, followed by brain, testis, and gut (15-30% the content of ovary). The
      muscle, fat body, and colleterial gland contained the lowest cyclophilin mRNA
      level (1-5% the content of ovary). There is a developmental pattern of gene
      expression affecting the embryo stages. These results suggest that this
      ubiquitously expressed B. germanica cyclophilin is subject to a differential
      regulation in tissues and during development. Southern-blot analysis of B.
      germanica DNA shows that only one copy of the CyPA gene is present per genome,
      whereas at least 20 genes or pseudogenes were detected in the mammalian genome.

PMID- 8529655
TI  - Structurally and functionally distinct Ca2+ binding sites in the gamma
      carboxyglutamic acid-containing domain of factor VIIa.
AB  - The structural and functional effects of Ca2+ binding to vitamin-K-dependent
      coagulation factor VIIa were investigated. Conformational changes with a midpoint
      around 0.7 mM Ca2+ quenched the intrinsic protein fluorescence of a fragment of
      factor VIIa comprising only the light chain and this coincided with an increase
      in factor VIIa amidolytic activity in the absence of tissue factor. Ca2+ binding
      to sites in factor VIIa and in the fragment with an apparent dissociation
      constant of 1.3-1.4 mM induced binding to phospholipids. A similar Ca2+
      dependency was not observed with factor VIIa lacking the N-terminal 38 or 44
      residues of the light chain and the observed effects could thus be attributed to
      gamma-carboxyglutamic-acid-dependent Ca2+ binding. Mg2+ appeared to bind to the
      site(s) of relatively higher affinity since, although it was less efficient than
      Ca2+, it stimulated the amidolytic activity and induced quenching of the
      intrinsic fluorescence. In contrast, Mg2+ did not induce expression of the
      phospholipid-interactive structure. The binding properties of two monoclonal
      antibodies that recognized epitopes in the gamma-carboxy-glutamic-acid-rich
      domain of factor VIIa corroborated the occurrence of two Ca(2+)-induced,
      sequential structural changes and only one of the antibodies recognized the
      Mg(2+)-induced structure. Thus Ca2+ binding to the gamma-carboxyglutamic-acid
      containing domain appeared to result in at least two distinct structural
      transitions with different functional consequences. The two (sets of) sites
      responsible for the observed effects could be distinguished based upon
      differences in Ca2+ affinity and metal ion selectivity. The interaction between
      factor VIIa and tissue factor was monitored by means of a direct binding assay
      and an amidolytic assay. In both systems, half-maximal Ca2+ enhancement was
      observed at 0.25 mM. This coincided with a Ca(2+)-induced conformational change
      in factor VIIa associated with fluorescence quenching. The same effect on
      amidolytic activity was observed with the two N-terminally truncated forms of
      factor VIIa and it is presumably mediated by Ca2+ binding to a site located in
      the serine protease part.

PMID- 8529656
TI  - Involvement of phosphorylase kinase inhibition in the effect of resorcinol and
      proglycosyn on glycogen metabolism in the liver.
AB  - The purpose of this study was to identify the mechanism by which proglycosyn and
      resorcinol decrease the phosphorylase a content and the fructose 2,6-bisphosphate
      concentration in isolated hepatocytes. The intracellular concentrations of the
      glucuronide derivatives of proglycosyn and resorcinol have been measured by HPLC
      in hepatocytes incubated for 5 min or 30 min with different concentrations of
      these agents. At both times, there was a reciprocal relationship between the
      phosphorylase a content and the intracellular concentration of the glucuronidated
      metabolites, half-maximal inactivation being observed at about 2 mumol/g protein
      and 0.25 mumol/g protein for resorcinylglucuronide and proglycosyn-glucuronide,
      respectively. Glycogen synthase was not significantly activated by these agents
      after 5 min but was well activated after 30 min. Preincubation of hepatocytes
      with 1 mM resorcinol or with 100 microM proglycosyn resulted in a decrease in the
      rate at which phosphorylase was activated following the addition of glucagon,
      vasopressin, the protein phosphatase inhibitor calyculin A or the calcium
      ionophore A 23187, but did not reduce the rate of synthase inactivation.
      Proglycosynglucuronide and resorcinylglucuronide inhibited phosphorylase kinase
      in liver Sephadex filtrates, with Ki values of about 0.75 mM and 4 mM,
      respectively. Preincubation of the filtrates with ATP and cAMP decreased the
      sensitivity of phosphorylase kinase to resorcinylglucuronide by about fourfold.
      It is concluded that the effect of resorcinol and proglycosyn on the
      phosphorylase a content is due, at least partly, to an inhibition of
      phosphorylase kinase by their glucuronidated metabolites. Resorcinol and
      proglycosyn caused a parallel decrease in the concentration of fructose 2,6
      bisphosphate and of hexose 6-phosphates, without significantly changing the
      activity of 6-phosphofructo-2-kinase. The decrease in the fructose 2,6
      bisphosphate concentration appears therefore to be secondary to the decrease in
      the hexose 6-phosphate concentration.

PMID- 8529657
TI  - Transcriptional activation and repression, two properties of the lymphoid
      specific transcription factor Oct-2a.
AB  - The lymphoid-specific transcription factor Oct-2a contains two transcriptional
      activation domains which are located within the N-terminal and C-terminal
      regions. To study their differential activation properties, we linked the
      isolated effector domains to the GAL4 DNA-binding domain. We have shown that both
      activating regions of Oct-2a, isolated from their natural context, can activate
      transcription as promoter factors. In contrast to the C-terminus, activation by
      the N-terminal domain is dependent on a yet unidentified factor(s) binding to the
      simian virus 40 enhancer. The results obtained by duplication of activation
      domains or their mixed combination suggest that the domains are functionally
      independent. However, activation from a remote position could only be achieved
      with the C-terminus of Oct-2a in B cells. In lymphoid cells, higher activation
      levels were observed, suggesting that distinct B-cell-specific cofactors in
      concert with the effector domains of Oct-2a might be involved in mediating
      transcription from proximal and remote positions. Furthermore, we identified a
      repression domain at the N-terminus of Oct-2a. When transferred to a potent
      activator, transcriptional stimulation was inhibited efficiently. These results
      underscore the modular structure of Oct-2a with separable domains for activation
      and repression and suggest that Oct-2a might have complex regulatory functions in
      vivo.

PMID- 8529658
TI  - Different susceptibility of protein kinases to staurosporine inhibition. Kinetic
      studies and molecular bases for the resistance of protein kinase CK2.
AB  - A systematic analysis reveals that out of 20 protein kinases examined, specific
      for either Ser/Thr or Tyr, the majority are extremely sensitive to staurosporine,
      with IC50 values in the low nanomolar range. A few of them however, notably
      protein kinases CK1 and CK2, mitogen-activated protein (MAP) kinase and protein
      tyrosine kinase CSK, are relatively refractory to staurosporine inhibition,
      exhibiting IC50 values in the micromolar range. With all protein kinases tested,
      namely PKA, CK1, CK2, MAP kinase (ERK-1), c-Fgr, Lyn, CSK and TPK-IIB/p38Syk,
      staurosporine inhibition was competitive with respect to ATP, regardless of its
      inhibitory power. In contrast, either uncompetitive or noncompetitive kinetics of
      inhibition with respect to the phosphoacceptor substrate were exhibited by
      Ser/Thr and Tyr-specific protein kinases, respectively, consistent with a
      different mechanism of catalysis by these two sub-families of kinases. Computer
      modeling based on PKA crystal structure in conjunction with sequence analysis
      suggest that the low sensitivity to staurosporine of CK2 may be accounted for by
      the bulky nature of three residues, Val66, Phe113 and Ile174 which are homologous
      to PKA Ala70, Met120 and Thr183, respectively. In contrast these PKA residues are
      either conserved or replaced by smaller ones in protein kinases highly sensitive
      to staurosporine inhibition. On the other hand, His160 which is homologous to PKA
      Glu170, appears to be responsible for the unique behaviour of CK2 with respect to
      a staurosporine derivative (CGP44171A) bearing a negatively charged benzoyl
      substituent: while CGP44171A is 10- 100-fold less effective than staurosporine
      against PKA and most of the other protein kinases tested, it is actually more
      effective than staurosporine for CK2 inhibition, but it looses part of its
      efficacy if it is tested on a CK2 mutant (H160D) in which His160 has been
      replaced by Asp. It can be concluded from these data that the catalytic sites of
      protein kinases are divergent enough as to allow a competitive inhibitor like
      staurosporine to be fairly selective, a feature that can be enhanced by suitable
      modifications designed based on the structure of the catalytic site of the
      kinase.

PMID- 8529659
TI  - Activation of two isoforms of mitogen-activated protein kinase kinase in response
      to epidermal growth factor and nerve growth factor.
AB  - Mitogen-activated protein kinase kinase (MAPKK) is a dual-specificity protein
      kinase which phosphorylates and activates mitogen-activated protein kinase
      (MAPK). cDNAs encoding two isoforms of MAPKK, MAPKK1 and MAPKK2 (also known as
      MEK1 and MEK2), have been cloned in mammalian cells. To analyze the
      characteristics of MAPKK1 and MAPKK2 individually, we have produced specific anti
      MAPKK serum against each isoform. MAPKK1 and MAPKK2 have apparent molecular
      masses of 45 kDa and 47 kDa, respectively, on SDS/polyacrylamide gel
      electrophoresis. In mouse tissues, MAPKK1 was highly enriched in brain, while
      MAPKK2 was present relatively evenly. In rat fibroblastic 3Y1 cells, epidermal
      growth factor (EGF) treatment induced activation of both MAPKK1 and MAPKK2.
      Immunoprecipitation experiments have shown that the time courses of activation
      and deactivation of both isoforms of MAPKK were superimposed. In PC12 cells, both
      MAPKK1 and MAPKK2 were activated in response to nerve growth factor (NGF) as well
      as EGF, and the time courses of activation and deactivation of both isoforms were
      indistinguishable from each other in the NGF-stimulated cells and also in the EGF
      stimulated cells. Furthermore, localization of both MAPKK1 and MAPKK2 in the
      cytoplasm was unchanged in response to EGF and NGF. Thus, the same or quite
      similar mechanisms may operate in the regulation of the activation and
      deactivation of two isoforms of MAPKK, and both kinases might have redundant
      functions when expressed in the same cell.

PMID- 8529660
TI  - Expression of a recombinant human glycosyltransferase from a synthetic gene and
      its utilization for synthesis of the human blood group B trisaccharide.
AB  - A 1034-bp synthetic gene encoding the human blood group B glycosyltransferase,
      which catalyzes the transfer of galactose from UDP-Gal to Fuc alpha(1-2)Gal beta
      OR to give the blood group B determinant Gal alpha(1-3)[Fuc alpha(1-2)]Gal beta
      OR (where R is a glycoprotein or glycolipid), has been expressed in Escherichia
      coli by replacing its membrane-anchoring domain with an ompA bacterial secretory
      signal. The active enzyme was purified from the periplasm using UDP-hexanolamine
      affinity chromatography and used in the synthesis of preparative amounts of the
      human blood group B trisaccharide antigen. The substrate specificity and kinetics
      of the recombinant enzyme were comparable to the enzyme from human sera. Thus we
      have achieved the construction of a completely synthetic glycosyltransferase gene
      and its successful expression.

PMID- 8529661
TI  - Intrinsic tryptophan fluorescence of equinatoxin II, a pore-forming polypeptide
      from the sea anemone Actinia equina L, monitors its interaction with lipid
      membranes.
AB  - Equinatoxin II is a cytolytic polypeptide from the sea anemone Actinia equina L.
      which forms pores in natural and artificial membranes. The intrinsic fluorescence
      of its five tryptophanyl residues was used to monitor the conformational changes
      induced by denaturing agents, pH and lipids. In the presence of denaturants, the
      emitted fluorescence peak, normally occurring at 335 nm, was reduced in height by
      about 65% and red-shifted to 354 nm indicating unfolding. The toxin fluorescence
      intensity reversibly decreased by increasing the pH, whereas lipid vesicles, at
      every pH, caused an increase and a blue shift. The amount of toxin binding to the
      lipid vesicle was increased by the presence of sphingomyelin. With sphingomyelin
      containing vesicles half-saturation occurred at a lipid/toxin molar ratio of
      about 40, whereas with phosphatidylcholine no saturation appeared up to a ratio
      of 300. One hydrophilic neutral quencher (acrylamide) and two lipid-confined
      phosphatidyltype quenchers [bis(9,10-dibromostearoyl)-sn-glycero-3-phosphocholine
      and 1-palmitoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine] were used to
      assess the exposure of the emitting centres to the solvent and/or to the lipid.
      Most of the indolyl residues were found to be solvent-exposed in the water
      soluble form of the toxin, as inferred from acrylamide quenching. Upon
      association with lipid vesicles, the fraction accessible to acrylamide dropped
      considerably, meanwhile the toxin became sensitive to lipid-soluble quenchers.
      Taken together these results suggest that insertion of equinatoxin II into
      sphingomyelin-containing bilayers is facilitated by high pH and results in the
      transfer of one or more exposed tryptophanyl residues into the liquid phase.
      Calcein-loaded vesicles, with or without a lipid quencher, were used to monitor
      simultaneously the formation of pores and the transfer of the tryptophans to the
      lipid phase. We found that the rate constants for vesicles permeabilization and
      for changes of intrinsic tryptophanyl fluorescence had a different dependence on
      the lipid/toxin ratio suggesting they correspond to separate steps in the toxin
      lipid interaction.

PMID- 8529662
TI  - Molecular cloning of the human glucose-regulated protein ERp57/GRP58, a thiol
      dependent reductase. Identification of its secretory form and inducible
      expression by the oncogenic transformation.
AB  - Recently it was shown that putative phospholipase C-alpha cDNA does not code for
      an isotype of the phospholipase C superfamily but for one of the glucose
      regulated proteins (GRPs), ERp57/GRP58. We have isolated human ERp57/GRP58 cDNA
      from human placenta. Sequence analysis showed that ERp57/GRP58 has two Trp-Cys
      Gly-His-Cys-Lys motifs completely conserved among the mammals. Bacterially
      expressed recombinant ERp57/GRP58 protein contained a thiol-dependent reductase
      activity which was completely abolished when Ser residues were substituted for
      Cys residues in both of the two motifs. Furthermore, we have identified a soluble
      form of ERp57/GRP58 by Western blotting and biosynthetic labeling. In v-onc
      transformants of normal rat kidney cells, the expression level of ERp57/GRP58 was
      elevated at the protein level. In NIH3T3 cells transformed with v-src, activated
      c-src (Y527F) or c-src, the expression level of ERp57/GRP58 was upregulated in
      proportion to their transforming abilities. These results indicate that a soluble
      form of ERp57/GRP58 exists and that this protein may control both extracellular
      and intracellular redox activities through its thiol-dependent reductase
      activity. Moreover, it is likely that ERp57/GRP58 is involved in the oncogenic
      transformation.

PMID- 8529663
TI  - Glycogen metabolism in quail embryo muscle. The role of the glycogenin primer and
      the intermediate proglycogen.
AB  - Cultured quail embryo muscle has proven to be an excellent model system for
      studying the synthesis of macromolecular glycogen from, and its degradation to,
      glycogenin, the autocatalytic, self-glucosylating primer for glycogen synthesis.
      We recently demonstrated that proglycogen, a low-M(r) form of glycogen, is an
      intermediate in the synthesis. Here we show that proglycogen also functions as an
      intermediate in macroglycogen degradation and, in one set of circumstances,
      represents an arrest point in glycogen breakdown, which does not continue to
      glycogenin. We suggest that in the nutritionally dependent turnover of glycogen
      in tissues, the molecules cycle between proglycogen and macromolecular glycogen
      and are not normally degraded to glycogenin. Nevertheless, when this does happen,
      the released glycogenin is active, capable of re-initiating glycogen synthesis.
      Under culture conditions where the conversion of proglycogen into glycogenin does
      take place, the intermediates lying between form a discrete rather than a
      continuous series, suggestive of a cluster structure for proglycogen and
      indicating that breakdown is stepwise. Evidence of post-translational
      modification of glycogenin was obtained by the finding that, in glycogen from
      cultured muscle, glycogenin is phosphorylated.

PMID- 8529664
TI  - Functional properties of a recombinant chimeric protein with combined thrombin
      inhibitory and plasminogen-activating potential.
AB  - A chimeric protein (rscu-PA-40-kDa/Hir), consisting of the C-terminal amino acids
      53-65 of hirudin (Hir), fused via a 14-amino-acid linker sequence to the C
      terminal of a 40-kDa fragment (Ser47-Leu411) of recombinant (r) single-chain (sc)
      urokinase-type plasminogen activator (rscu-PA), was produced by expression of the
      corresponding chimeric cDNA in Escherichia coli cells. The thrombin inhibitory
      potential of purified rscu-PA-40-kDa/Hir was confirmed by complete inhibition of
      the coagulant activity of thrombin at 20-30-fold molar excess of the chimera, and
      by the resistance of rscu-PA-40-kDa/Hir to proteolytic cleavage by thrombin, rscu
      PA-40-kDa/Hir prolonged the thrombin time of normal human plasma in a dose
      dependent way (reduction of the apparent thrombin concentration to 50% with 95 nM
      chimeric protein as compared to 4.7 nM hirudin), and inhibited thrombin-mediated
      platelet aggregation (reduction of the apparent thrombin concentration to 50%
      with 40 nM chimeric protein). The chimera had a specific activity on fibrin films
      of 57,000 IU/mg as compared to 95,000 IU/mg for rscu-PA. The urokinase-like
      amidolytic activity of the single-chain protein was only 220 IU/mg but increased
      to 169,000 IU/mg after treatment with plasmin, which resulted in quantitative
      conversion to a two-chain (tc) derivative (rtcu-PA-40-kDa/Hir). Corresponding
      values for rscu-PA were 270 and 226,000 IU/mg. The catalytic efficiencies for
      plasmin-mediated conversion to two-chain molecules were comparable for rscu-PA-40
      kDa/Hir and rscu-PA (0.63 and 0.65 microM-1.s-1, respectively). The plasminogen
      activating potential of the single-chain chimera was comparable to that of rscu
      PA; the catalytic efficiencies for plasminogen activation by their two-chain
      counterparts were also similar (0.55 and 0.73 microM-1.s-1, respectively). In 2
      h, 50% lysis of 125I-fibrin-labeled clots prepared from platelet-poor human
      plasma and immersed in normal plasma was obtained with 1.3 micrograms/ml rscu-PA
      40-kDa/Hir and with 0.67 micrograms/ml rscu-PA, with corresponding residual
      fibrinogen levels of 74% and 87%, respectively. In the absence of fibrin, 50%
      fibrinogenolysis in 2 h in normal human plasma required 2.1 micrograms/ml rscu
      PA, but 7.9 micrograms/ml rscu-PA-40-kDa/Hir. Thus, the chimera rscu-PA-40
      kDa/Hir has maintained the specific fibrinolytic and plasminogen activating
      activity of rscu-PA as well as its fibrinolytic potency in plasma, whereas it
      displayed a similar or somewhat better fibrin specificity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8529666
TI  - Regulation of the expression of cathepsin B in Sarcophaga peregrina (flesh fly)
      at the translational level during metamorphosis.
AB  - Previously, we reported that cathepsin B of pupal hemocytes participates in
      dissociation of the fat body of Sarcophaga larvae at metamorphosis. In this
      study, we demonstrated that the amount of cathepsin B in hemocytes was controlled
      at the translational level, i.e. larval hemocytes stored a significant amount of
      untranslated cathepsin B mRNA. When the larvae pupated, translation of the mRNA
      commenced, resulting in accumulation of cathepsin B. Our results indicate that
      the 3'-untranslated region (3'-UTR) of this mRNA is necessary for the repression
      of its translation in a rabbit reticulocyte lysate. We detected the 3'-UTR
      binding protein in the lysate of larval hemocytes, but not in the pupal
      hemocytes. The role of this protein in the translation of cathepsin B mRNA is
      discussed.

PMID- 8529665
TI  - Identification of Trp300 as an important residue for Escherichia coli leader
      peptidase activity.
AB  - We previously reported that leader peptidase from Escherichia coli was
      extensively inactivated by reaction with N-bromosuccinimide with concomitant and
      selective modification of the Trp300 and Trp310 residues [Kim, Y.-T., Muramatsu,
      T. & Takahashi, K. (1995) J. Biochem. (Tokyo) 117, 535-544]. This indicated that
      one or both of these tryptophan residues are important for the activity of the
      enzyme. In order to define further the role of individual tryptophan residues in
      the activity of leader peptidase, site-directed mutagenesis studies were
      performed to replace each tryptophan residue with phenylalanine and/or alanine.
      The replacements of Trp20, Trp59, Trp261, Trp284, and Trp310 with phenylalanine
      hardly affected the enzyme activity toward a synthetic peptide substrate and the
      ability to complement the temperature sensitivity of the mutant leader peptidase
      in E. coli IT41. In contrast, the activity toward the synthetic substrate was
      significantly decreased by replacement of Trp300 with phenylalanine or alanine.
      The kcat values of the W300F and W300A mutant enzymes were reduced to 42% and
      22%, respectively, of that of the wild-type enzyme, whereas the Km values of
      these mutant enzymes were almost identical with that of the wild-type enzyme.
      Moreover, the complementing ability in E. coli IT41 was lost (almost) completely
      when Trp300 was replaced with phenylalanine or alanine. These results strongly
      indicate that Trp300 in leader peptidase is important for the catalytic mechanism
      and/or the construction of the active site structure of the enzyme.

PMID- 8529667
TI  - A specific template-assembled peptidic agonist for the angiotensin II receptor
      subtype 2 (AT2) and its effect on inferior olivary neurones.
AB  - We synthesized a molecule composed of two angiotensin II 4-8 pentapeptide
      fragments attached to a carrier molecule (TA), according to the template
      assembled synthetic proteins concept. This molecule was investigated for receptor
      binding on angiotensin type-1 and type-2 receptors (AT1 and AT2) and its
      biological activity was determined by iontophoretic experiments on neurones of
      the inferior olive (ION) that express only AT2 receptors. TA binds exclusively to
      the AT2 receptor and mediates an agonistic angiotensin-II effect on the ION. TA
      is the first agonist available to study the direct stimulation of AT2 receptors.

PMID- 8529668
TI  - Phosphorylation of calmodulin by plasma-membrane-associated protein kinase(s).
AB  - Plasma-membrane-associated protein kinase(s) from normal rat liver phosphorylates
      exogenous bovine brain calmodulin in the absence of Ca2+ and in the presence of
      histone or poly(L-lysine). Maximum levels of calmodulin phosphorylation are
      obtained at a poly(L-lysine)/calmodulin molar ratio of 0.4. Phosphoamino acid
      analysis revealed that calmodulin is phosphorylated on serine, threonine and
      tyrosine residues. Endogenous plasma-membrane-associated calmodulin was also
      phosphorylated by plasma-membrane-associated protein kinase(s) in the absence of
      added cationic protein or polypeptide. The identity of endogenous
      phosphocalmodulin was confirmed by immunoprecipitation with a specific anti
      calmodulin monoclonal antibody. Ehrlich ascites tumor cell plasma membranes do
      not contain endogenous calmodulin. However, membrane-associated protein kinase(s)
      from these tumor cells phosphorylates bovine brain calmodulin in the presence of
      poly(L-lysine). These data demonstrate that phosphocalmodulin is present in liver
      plasma membranes and suggest that this post-translational modification could have
      a physiological role in this location.

PMID- 8529669
TI  - Characterization of two genes coding for a similar four-cysteine motif of the
      amino-terminal propeptide of a sea urchin fibrillar collagen.
AB  - We report the characterization of the 5' region of the gene coding for the 2
      alpha fibrillar collagen chain of the sea urchin Paracentrotus lividus. This
      sequence analysis identified the intron/exon organization of the region of the
      gene coding for the signal peptide, the cysteine-rich domain and the 12 repeats
      of the four-cysteine module of the unusually long amino-propeptide. This still
      unknown four-cysteine motif is generally encoded by one exon, which confirms that
      the distinct amino-propeptide structures of the fibrillar collagens arise from
      the shuffling of several exon-encoding modules. Moreover, Southern-blot analysis
      of the sea urchin genome and sequencing of selected genomic clones allowed us to
      demonstrate that several sea urchin genes could potentially code for the four
      cysteine module. Curiously, one of these genes lacks the exons coding for four
      repeats of this motif while, in another gene, the same exons are submitted to an
      alternative splicing event.

PMID- 8529670
TI  - Purification and properties of human placental ATP diphosphohydrolase.
AB  - ATP diphosphohydrolase activity (ATP-DPH) has been previously identified in the
      particulate fraction of human term placenta [Papamarcaki, T. & Tsolas, O. (1990)
      Mol. Cell. Biochem. 97, 1-8]. In the present study we have purified to
      homogeneity and characterized this activity. A 260-fold purification has been
      obtained by solubilization of the particulate fraction and subsequent
      chromatography on DEAE Sepharose CL-6B and 5'-AMP Sepharose 4B. The preparation
      has been shown to be free of alkaline phosphatase even though the placental
      extract is rich in this activity. The purified enzyme is a glycoprotein and
      migrates as a single broad band of 82 kDa on SDS/PAGE. The same band is obtained
      after photoaffinity labeling of the enzyme with 8-azido-[alpha-32P]ATP. The
      enzyme has a broad substrate specificity, hydrolyzing triphosphonucleosides and
      diphosphonucleosides but not monophosphonucleosides or other phosphate esters.
      The activity is dependent on the addition of divalent cations Ca2+ or Mg2+. The
      Km values for ATP and ADP were determined to be 10 microM and 20 microM,
      respectively. Maximum activity was found at pH 7.0-7.5 with ATP as substrate, and
      pH 7.5-8.0 with ADP. The enzymic activity is inhibited by NaN3, NaF, adenosine 5'
      [beta,gamma-imido]triphosphate and adenosine 5'-[alpha,beta
      methylene]triphosphate. Protein sequence analysis showed ATP-DPH to be N
      terminally blocked. Partial internal amino acid sequence information was obtained
      after chymotryptic cleavage and identified a unique sequence with no significant
      similarity to known proteins. ATP-DPH activity has been reported to be implicated
      in the prevention of platelet aggregation, hydrolysing ADP to AMP and thus
      preventing blood clotting.

PMID- 8529671
TI  - The signal transduction pathway of erythropoietin involves three forms of mitogen
      activated protein (MAP) kinase in UT7 erythroleukemia cells.
AB  - The survival and proliferation of the UT-7 human leukemic cell line is strictly
      dependent on the presence of either interleukin 3, granulocyte-macrophage colony
      stimulating factor or erythropoietin. In these cells, erythropoietin stimulation
      led to the rapid phosphorylation of several proteins including the erythropoietin
      receptor and proteins with molecular masses around 45 kDa which could be mitogen
      activated protein (MAP) kinases. Separation of cytosol from resting or
      erythropoietin-stimulated UT-7 cells by anion-exchange chromatography revealed
      two peaks of myelin basic protein kinase activity. The kinase activity of the
      first peak was independent of erythropoietin treatment of the cells and
      corresponded to an unidentified 50-kDa kinase, whereas the second peak was only
      present in erythropoietin-stimulated cells and corresponded to three forms of MAP
      kinases with molecular masses of 45, 44 and 42 kDa. The three forms were
      separated by hydrophobic chromatography and were shown to be activated in
      erythropoietin-stimulated cells. The 44-kDa and 42-kDa forms corresponded to
      extracellular signal-regulated kinase (ERK)-1 and ERK-2, respectively. Evidence
      was obtained showing that the 45-kDa form is not a shifted form of ERK-1 but
      corresponded to a less well defined form of MAP kinase which may be the
      previously described ERK-4. MAP kinase activation was detected after 1 min
      erythropoietin stimulation and remained detectable after more than 1 hour. A role
      for MAP kinase activation in erythropoietin-stimulated cell proliferation was
      suggested by the simultaneous inhibition of erythropoietin-induced MAP kinase
      stimulation and cell proliferation. The potential activator of MAP kinase, RAF-1,
      was hyperphosphorylated in erythropoietin-stimulated cells and its
      autophosphorylation activity was strongly increased. The protein adaptor Shc was
      heavily phosphorylated in UT-7 erythropoietin-stimulated cells and associated
      strongly with a unidentified 145-kDa protein. However, Shc bound poorly to the
      activated erythropoietin receptor and most Shc proteins were cytosolic in both
      unstimulated and erythropoietin-stimulated cells. In contrast, Grb2 associated
      efficiently with the activated erythropoietin receptor and a significant part of
      Grb2 was associated to a particulate subcellular fraction upon erythropoietin
      stimulation.

PMID- 8529672
TI  - Isolation of a novel cDNA that encodes a protein localized to the pre-acrosome
      region of spermatids.
AB  - We have identified a novel cDNA clone, named AZ1, obtained from a cDNA library of
      mRNA prepared from C3H10T1/2 cells that had been transiently exposed to 5
      azacytidine, a potent demethylating reagent. The amount of transcript increased
      with 5-azacytidine treatment of C3H10T1/2 cells and the transcript was highly
      expressed in mouse testis. As the mutant mouse jsd/jsd, which has a defect in
      germ cell maturation, barely expressed the transcript, the message was expected
      to be expressed specifically in spermatocytes. The mRNA was detected at
      significant levels in the testes from mice aged 16 days after birth, suggesting
      that its expression started at the pachytene spermatocyte stage. The elucidated
      nucleotide sequence contained a 2841-nucleotide open reading frame, and the
      expected amino acid sequence had a molecular mass of 107,254 Da. Specific
      antibodies raised against the fusion protein including glutathione S-transferase
      revealed an approximately 130-kDa band of a translation product in testis and in
      cultured cells transfected with AZ1 cDNA in the expression vector on Western-blot
      analysis. The protein was localized to the pre-acrosome region of round and
      elongated spermatids. However, it was not detected at a more advanced stage of
      spermatids, i.e. just before their release from Sertoli cells. This protein may
      play an important role in spermatogenesis.

PMID- 8529673
TI  - Phosphotyrosine residues in the nerve-growth-factor receptor (Trk-A). Their role
      in the activation of inositolphospholipid metabolism and protein kinase cascades
      in phaeochromocytoma (PC12) cells.
AB  - PC12 cells, which lack platelet derived-growth-factor (PDGF) receptors, have been
      stably transfected with a chimaera consisting of the extracellular domain of the
      beta-PDGF receptor and the intracellular and transmembrane domains of the nerve
      growth-factor receptor Trk-A (termed PT-R). Mutation of the Trk-A residue Tyr490
      to phenylalanine prevents the association with Shc, while similar mutations at
      Tyr751 or Tyr785 are reported to prevent interaction of Trk-A with the p85
      subunit of inositol phospholipid 3-kinase and phospholipase C-gamma 1,
      respectively. The strong and sustained activation of p42 and p44 mitogen
      activated-protein kinases induced by PDGF-B/B in PC12/PT-R cells was unaffected
      by mutation of Tyr785 or Tyr751 to phenylalanine, but was smaller and transient
      after mutation of Tyr490, and almost abolished by the double mutation of Tyr490
      and Tyr785. Mutation of Tyr490 reduced by 70% the PDGF-induced increase in
      inositol phospholipid 3-kinase activity immunoprecipitated from cell extracts
      with antiphosphotyrosine monoclonal antibodies and greatly suppressed the PDGF
      induced increase in the intracellular products of inositol phospholipid 3-kinase,
      while mutation of Tyr751 or Tyr785 had no effect. Mutation of Tyr785 (but not
      mutation of Tyr490 or Tyr751) abolished PDGF-stimulated hydrolysis of
      phosphatidylinositol 4,5-bisphosphate. Mutation of Tyr490, alone or in
      combination with mutation of Tyr751 and Tyr785, had no effect on the PDGF-induced
      activation of p70 S6 kinase (p70S6K). However, the activation of p70S6K by PDGF
      (or nerve growth factor), but not the activation of mitogen-activated-protein
      kinase, was prevented by two structurally unrelated inhibitors of inositol
      phospholipid 3-kinase, wortmannin or LY294002. Our results demonstrate the
      following: (1) the phosphorylation of Tyr490 plays a major role in the activation
      of inositol phospholipid 3-kinase and formation of 3-phosphorylated inositol
      lipids and confirm that the phosphorylation of Tyr 785 triggers the activation of
      phospholipase C-gamma 1 in vivo. (2) Tyr490 phosphorylation (but not inositol
      phospholipid 3-kinase activation) is also required for strong and sustained
      activation of mitogen-activated-protein kinase and neuronal differentiation,
      while the smaller and more transient activation of mitogen-activated-protein
      kinase, produced by the activation of phospholipase C-gamma 1 is insufficient to
      trigger the neuronal differentiation of PT-R cells. (3) Inositol phospholipid 3
      kinase is required for the activation of p70S6K, but only a small increase in
      inositol phospholipid 3-kinase activity and the level of 3-phosphorylated
      inositol lipids is required for maximal p70S6K activation.

PMID- 8529674
TI  - Diphenylene iodonium inhibits the induction of erythropoietin and other mammalian
      genes by hypoxia. Implications for the mechanism of oxygen sensing.
AB  - Recent studies on the induction of erythropoietin gene expression by hypoxia have
      indicated that erythropoietin forms part of a widely operative system of gene
      regulation by oxygen. Similar responses to hypoxia, cobaltous ions and
      desferrioxamine have indicated that the action of these agents is closely
      connected with the mechanism of oxygen sensing. To consider further the
      mechanisms underlying these responses, the effect of iodonium compounds was
      tested on five genes which show oxygen-regulated expression; erythropoietin,
      vascular endothelial growth factor (VEGF), lactate dehydrogenase-A (LDH-A),
      glucose transporter-1 (GLUT-1) and placental growth factor (PLGF). In each case,
      the response to hypoxia was specifically inhibited by low doses of diphenylene
      iodonium (Ph1I+). This occurred irrespective of whether the hypoxic response was
      induction of gene expression (erythropoietin, vascular endothelial growth factor,
      lactate dehydrogenase-A, glucose transporter-1) or inhibition of gene expression
      (PLGF). In contrast, the induction of gene expression by cobaltous ions or
      desferrioxamine was not inhibited by Ph2I+. The differential action of Ph2I+ on
      the response to hypoxia versus the response to cobaltous ions or desferrioxamine
      must reflect a difference in the mechanism of action of these stimuli, which will
      require accommodation in any model of the oxygen-sensing mechanism. Based on the
      known properties of Ph2I+, the implication of these findings is that the
      mechanism of oxygen sensing most probably involves the operation of a
      flavoprotein oxidoreductase.

PMID- 8529676
TI  - Serial cardiorespiratory exercise testing in patients with congenital heart
      disease.
AB  - Aerobic capacity of patients with different forms of congenital heart disease was
      serially evaluated in 79 patients and the evolution was correlated with the
      lesion and the level of daily activity. The patients were divided into six
      groups: patients with a small ventricular septal defect (VSD) with mini shunt (n
      = 14), mild pulmonary valve stenosis with gradient < 40 mm Hg (PS) (n = 12), mild
      to moderate aortic valve stenosis (gradient 36 +/- 17 mmHg) (AS) (n = 12),
      patients 4.7 +/- 2.1 years after repair of tetralogy of Fallot (PO-TF) (n = 16),
      patients 2.2 +/- 2.9 years after closure of a high flow/high gradient VSD (PO
      VSD) (n = 13), and patients 2.6 +/- 1.7 years after Fontan repair (Fontan-PO) (n
      = 12). Aerobic capacity was assessed by determination of the ventilatory
      anaerobic threshold (VAT). VAT reflects the highest aerobic exercise level prior
      to a disproportionate increase of CO2 and ventilation relative to O2 uptake; it
      is independent of patient motivation. Data are expressed as percentage of normal
      O2 uptake at VAT, determined in 234 age/gender matched controls. The habitual
      level of physical activity was assessed by a standardised questionnaire. Aerobic
      capacity in all subgroups of patients, even with very mild defects, was at or
      below the lower limit of normal. Children left unrestricted from physical
      exercise (VSD, PS, PO-VSD) had no change over the study period. However, aerobic
      capacity of patients with medically imposed physical restrictions (AS) and
      significant residual haemodynamic lesions (PO-TF, Fontan) decreased with
      age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529675
TI  - Aniridia: recent achievements in paediatric practice.
AB  - Aniridia is a rare panocular disorder which primarily involves not only the iris,
      but also the retina, optic nerve, lens and cornea. Visual acuity deteriorates as
      a result of nystagmus, glaucoma, cataract, corneal opacities and retinal
      hypoplasia. Aniridia may appear as an isolated disorder, most often familial with
      autosomal dominance or sporadically in association with at least 12 syndromes.
      Both familial isolated and Wilms tumour, bilateral sporadic aniridia,
      genitourinary abnormalities and mental retardation syndrome-associated aniridia
      have been traced to a mutation of the PAX6 gene on band 11p13. Since genetic
      diagnosis of this disorder is already possible, counselling affected families
      should be preceded by karyotype studies and linkage analysis in familial cases of
      isolated aniridia. In sporadic cases of isolated aniridia or WAGR syndrome, we
      suggest that PAX6 mutation analysis be employed.

PMID- 8529677
TI  - Effect of oestrogen/gestagen replacement therapy on liver enzymes in patients
      with Ullrich-Turner syndrome.
AB  - The absence of breast development and the prevention of osteoporosis in Ullrich
      Turner syndrome (UTS) require oestrogen/gestagen substitution therapy. In 8 out
      of 35 (23%) patients with UTS treated with conjugated equine oestrogens and
      cyclically with norethisterone acetate, the serum liver enzymes increased to
      conspicuous levels (AST 35; 20-73 U/l, ALT 92; 37-141 U/l, GGT 77; 25-227 U/l,
      [median; min-max]). These findings were compared with those in 41 tall girls who
      received a six-fold larger dose of conjugated equine oestrogens for the reduction
      of final height. None of these 41 girls showed abnormal serum liver enzyme
      levels. The conspicuous rise in serum liver enzyme levels occurred in the
      majority of the UTS patients before norethistherone acetate was added to the
      oestrogen replacement therapy. No essential morphological equivalent was found in
      liver sonography and biopsy studies. During the follow up the elevated serum
      liver enzyme levels showed reversibility when medication was temporarily
      discontinued and either a slow decrease or a steady state after therapy was
      continued. CONCLUSION. Patients with UTS on oral oestrogen replacement therapy
      are more susceptible to develop increased serum liver enzyme levels as compared
      with eukaryotic females treated with the same oestrogen preparation for other
      disorders. As the underlying pathomechanism is unknown and adverse long-term
      effects cannot be ruled out, avoiding the portal vein and using the transdermal
      application of oestrogen may represent a viable solution to the problem.

PMID- 8529678
TI  - Transient incidental glucosuria in children.
AB  - A consecutive series of 78 children with transient asymptomatic glucosuria was
      studied and followed up for up to 7.3 years. The age at presentation was 0.9-17.6
      (median 4.6) years. One third of the patients had random blood glucose levels of
      > 10.0 mmol/l (180 mg/dl). Five patients (6.4%) developed insulin-dependent
      diabetes mellitus within 2.1 years after the first incident of glucosuria. These
      patients presented with higher levels of glycaemia than others, and three out of
      five were positive for islet cell antibodies with a first-phase insulin response
      < 46 mU/l in all four studied. Of the remaining 73 children, 3 were positive for
      islet cell antibodies and 12/55 had a first-phase insulin response under 46 mU/l.
      The insulin response deteriorated in 3 but reverted to normal in 7 patients.
      CONCLUSION. For a child with transient glucosuria and with presence of islet cell
      antibodies and a subnormal first-phase insulin response, therapeutic attempts to
      prevent overt insulin-dependent diabetes mellitus should be considered.

PMID- 8529679
TI  - Isolated cerebral thrombo-embolism and Crohn disease.
AB  - Arterial thrombo-embolism is an unusual complication in inflammatory bowel
      disease in adults and children. Cerebral arterial disease has been reported on
      only a few occasions. There are only two previous case reports of arterial
      disease occurring in a child with Crohn disease. However in both instances the
      arterial disease was part of a generalised Takayasu arteritis which resulted in
      multi-organ involvement. This report describes a 14-year-old boy who developed
      seizures before a histological diagnosis of Crohn disease was made. These
      seizures were the result of a vascular lesion which was confined to the right
      middle cerebral artery. CONCLUSION. Crohn disease as well as ulcerative colitis
      should be considered as a possible cause of cerebrovascular accidents in
      children.

PMID- 8529680
TI  - A fatal case of portal hypertension complicating systemic mastocytosis in an
      adolescent.
AB  - Portal hypertension was observed in a 17-year-old girl with urticaria pigmentosa
      since 2 months of age. Liver biopsies showed portal and sinusoidal infiltration
      with mast cells although spleen biopsies showed only fibrosis. CONCLUSION. Portal
      hypertension is a complication of systemic mastocytosis that can lead to death.
      Treatment with interferon alpha might be effective.

PMID- 8529681
TI  - Growth of children with Langerhans cell histiocytosis.
AB  - Diseases in childhood have an impact on growth. The influence of Langerhans cell
      histiocytosis (LCH) on growth has never been studied well. Recently a patient
      with LCH was treated with human growth hormone (GH) because of severe GH
      deficiency due to LCH involvement of both the hypothalamus and pituitary. This
      led us to review our charts from 1971 onward for evaluation of the growth
      patterns in patients with LCH. Here the long-term growth of 22 patients with LCH
      is reported, the median follow up being 7 years and 1 month. The height data were
      converted into standard deviation scores (SDS). At diagnosis the mean SDS of
      patients with isolated LCH at diagnosis was 0.04 and -0.37 in patients with
      disseminated LCH. Of the total group, 12 patients did not show any influence from
      the LCH or therapy on their growth. The remaining 10 patients reached, after a
      minimum of 3 years, a percentile clearly higher than that at diagnosis. However
      all the ten above mentioned patients, either isolated or disseminated LCH, had a
      lesion in the facial side of the skull. CONCLUSION. GH deficiency is not a common
      manifestation of LCH in childhood and GH provocation tests are only indicated
      when there is a poor or decelerating growth rate. In our patients the number of
      organs involved and/or the treatment modality did not influence the growth in all
      but one.

PMID- 8529682
TI  - Soluble CD23 antigen in Kawasaki disease and other acute febrile illnesses.
AB  - Kawasaki disease (KD) is an acute febrile illness of early childhood. Although
      the epidemiology of KD suggests an infectious agent, the cause still remains
      unknown. Intense immune activation during the acute disease has been well
      documented. Quantitative determination of soluble CD23 in serum can serve as an
      index of macrophage/monocyte or B-cell activation. To further characterize the
      immunological profile in KD, we investigated whether soluble CD23 levels in serum
      increase during the acute disease. In addition, we compared soluble CD23 levels
      in 33 patients with acute KD with levels in ten patients each with measles,
      rubella, infectious mononucleosis, and scarlet fever to determine if marked
      elevations in soluble CD23 were unique to acute KD. Patients with KD, rubella and
      infectious mononucleosis, but not patients with measles or scarlet fever, had
      increased soluble CD23 levels in serum during the acute stage, as compared to age
      matched control subjects (P < 0.01). These data suggest infection with Epstein
      Barr virus and rubella and acute KD are all characterized by B-cell and
      macrophage/monocyte activation.

PMID- 8529683
TI  - Atypical Kawasaki disease with peripheral gangrene and myocardial infarction:
      therapeutic implications.
AB  - We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by
      peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to
      gangrene is a rare but serious complication of KD in infants younger than 7
      months of age. Treatment has been targeted at reducing arterial inflammation,
      arteriospasm and thrombosis. We report the first patient with incomplete KD and
      peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating
      and antithrombotic agent appeared successful, restoring hand and foot perfusion
      without significant long-term sequelae. However, PGE1 could have supported
      development of myocardial infarction by shunting blood away from ischaemic areas
      distal to a giant coronary artery aneurysm with beginning thrombosis. CONCLUSION.
      Atypical KD with peripheral gangrene appears to react favourably to treatment
      with PGE1, but needs careful monitoring to detect early signs of cardiac
      ischaemia.

PMID- 8529684
TI  - Arthrogryposis, renal dysfunction and cholestasis syndrome: report of five
      patients from three Italian families.
AB  - We report on five patients from three families with neurogenic arthrogryposis,
      cholestasis and tubular renal dysfunction. Despite a similar clinical picture the
      liver histology showed a broad pathological spectrum, ranging from pigment
      storage to parenchymal giant cell transformation and ductopenia. The findings are
      compared with those of other cases from the literature in search of a correct
      nosology of the syndrome characterized by arthrogryposis, renal and liver
      disease. CONCLUSION. We propose to consider the picture of arthrogryposis, renal
      tubular dysfunction and cholestasis as a single syndrome.

PMID- 8529685
TI  - Variability of clinical and immunological phenotype in immunodeficiency
      centromeric instability-facial anomalies syndrome. Report of two new patients and
      review of the literature.
AB  - Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a
      condition characterized by variable combined immunodeficiency, developmental
      delay, facial anomalies and a variety of structural chromosomal rearrangements.
      Recently, aberrations at the molecular level have been described consisting of
      alterations in the methylation pattern of classical satellite DNA. To our
      knowledge 15 subjects have been described so far in the literature showing marked
      phenotypic variability. We report on two new patients with normal development and
      some peculiar clinical and immunological manifestations. All patients previously
      reported in the literature are reviewed. CONCLUSION. The identification of these
      two cases among our hypogammaglobulinaemic patients suggests that ICF syndrome is
      not a rare disorder and it should be always taken into account in immunodeficient
      patients with facial abnormalities.

PMID- 8529686
TI  - No reduction in birth weight in phenylketonuria.
AB  - Birth weight in a total of 1886 British infants with phenylketonuria (PKU) born
      between 1964 and 1992 was examined in relation to sex, social class, gestational
      age, disease severity and birth year. Comparisons were made with two national
      surveys (British births 1970 and Office of Population Censuses and Surveys 1981).
      In contrast to a recent Dutch study, birth weight in British infants with PKU
      (mean 3307 g, median 3337 g) showed a similar distribution to population norms.
      Birth weight showed no temporal trends and no trends with disease severity.
      CONCLUSION. Birth weight is not reduced in British infants with PKU.

PMID- 8529687
TI  - Use of human somatotrophin in the treatment of a patient with methylmalonic
      aciduria.
AB  - Growth hormone (GH) insufficiency was demonstrated in a patient with
      methylmalonic aciduria. GH administration at 14-21 U/m2 per week accelerated
      linear growth, stimulated lipolysis, and produced clinical improvement and
      reduced urinary methylmalonate excretion. The clinical and metabolic benefits
      were lost as the dose of GH was increased to 28 U/m2 per week. CONCLUSION. The
      use of GH in other patients with methylmalonic aciduria (and other disorders of
      intermediary metabolism demonstrating similar clinical and metabolic features)
      warrants further study.

PMID- 8529689
TI  - Impact of community educational programmes on foreign body aspiration in Israel.
AB  - The study objectives were to determine the impact of a nationwide educational
      campaign on the incidence of foreign body aspiration (FBA) in Israeli children.
      Impressed by the alarming number of FBAs, we conducted an educational campaign
      through the media during 1982-1983. The campaign included television and radio
      broadcasts, newspaper articles and interviews, and medical educational programmes
      in community paediatric care centres. Questionnaires were sent to all Departments
      of Paediatrics in Israel. Results showed a reduction in the incidence of FBA by
      35% in 1983 as compared to 1981. Re-evaluation studies conducted in 1992 showed
      no further reduction of FBA. CONCLUSION. Continuous and extensive educational
      programmes should be undertaken by the health authorities if FBA is to be
      prevented. Furthermore, it is important to legislate mandatory labelling of seed
      and nut containers with the warning that the intake of seeds is dangerous to
      children under 5 years of age.

PMID- 8529691
TI  - Passive HIV-hyperimmunoglobulin therapy in paediatric AIDS.

PMID- 8529690
TI  - Case of the month. Colonic duplication.

PMID- 8529688
TI  - Cardiopulmonary function in premature infants with bronchopulmonary dysplasia--a
      2-year follow up.
AB  - Twenty-three premature infants (GA 28.8 +/- 0.5 weeks) with bronchopulmonary
      dysplasia (BPD) and 14 premature infants (controls, GA 33.0 +/- 1.2 weeks) with
      moderate respiratory distress syndrome or with mild respiratory disturbances,
      were evaluated for impairment of cardiopulmonary function at 50 and 120 weeks
      corrected age. Respiratory system compliance was reduced in both groups, but
      improved with advancing age. Respiratory system resistance was initially
      increased, especially in the BPD group, but improved gradually. Maximum flow at
      functional residual capacity (VmaxFRC ml/s) indicated, nevertheless, severe
      peripheral obstruction (flow < 84 ml/s) in 16/20 of infants with BPD and in 7/12
      of control infants at 50 weeks corrected age. At 120 weeks corrected age none of
      the control patients had severe peripheral pulmonary obstruction (flow < 120
      ml/s), while this was still found in 5/13 infants with BPD. Doppler
      echocardiography indicated cardiac involvement (shortened pulmonary acceleration
      time) in patients with the most severe peripheral pulmonary obstruction.
      Pulmonary morbidity was also higher in the BPD group, and these infants were
      shorter and weighed less than the control infants. CONCLUSION. Measurements of
      maximum flow at functional residual capacity as well as cardiac evaluation are
      essential elements in follow up of infants with severe BPD.

PMID- 8529692
TI  - Normal serum levels of vitamin B12 and folic acid in children with
      phenylketonuria.

PMID- 8529693
TI  - Aseptic meningitis: a frequent side-effect of intravenous immunoglobulin?

PMID- 8529694
TI  - Effect of glycerol trioleate oil milk formula administration on very long chain
      fatty acid levels and clinical course in a patient with Zellweger syndrome.

PMID- 8529695
TI  - Kawasaki disease in dizygotic twins.

PMID- 8529696
TI  - Metabolic alkalosis with hypo-electrolytaemia or pseudo-Bartter syndrome as a
      presentation of cystic fibrosis in infancy. Discription of three cases.

PMID- 8529697
TI  - The effect of furosemide on a patient with hyperkalaemic hypertension and short
      stature.

PMID- 8529698
TI  - Can paediatrics be kept vivacious in future?

PMID- 8529699
TI  - Living pediatrics. Symposium in honour of the 80th birthday of Professor E.
      Rossi, Berne, Switzerland.

PMID- 8529700
TI  - Paediatric gastro-enterology: out of children's shoes?

PMID- 8529701
TI  - Assessment of lung function in infants and young children with lung disease.

PMID- 8529703
TI  - Current concepts of bacterial meningitis.

PMID- 8529702
TI  - From observation to experimentation: lessons from the past.

PMID- 8529704
TI  - Practical paediatrics in a general district hospital.

PMID- 8529705
TI  - Forty years of paediatric research in inborn errors of metabolism.

PMID- 8529708
TI  - The value of family investigations in newly detected Charcot-Marie-Tooth disease
      in children.
AB  - Charcot-Marie-Tooth disease (CMT) was diagnosed by nerve conduction velocity and
      histology of the sural nerve in two boys aged 3 and 6 years with clinical signs
      of a severe neuromuscular disease. DNA analysis revealed the typical duplication
      on chromosome 17p11.2 (2.7 kb allele) for CMT 1A. Although none of their family
      members reported symptoms of neuromuscular disease, the nerve conduction velocity
      was reduced in three members (father and two aunts). They were homozygous for the
      2.7 kb allele and were assumed to carry three copies of this allele. The very
      differing clinical picture from one generation to the next in patients with
      identical neurophysiological and genetic results is discussed.

PMID- 8529707
TI  - Molecular biology and its application in paediatric endocrinology.
AB  - Recent advances in molecular biology and genetics have paved the way to a greater
      understanding of molecular mechanisms of human disease and, in particular,
      endocrine disorders. For example, new information concerning the structure and
      function of different receptors and intracellular signalling has allowed precise
      definition of the molecular defects involved in various disorders such as McCune
      Albright syndrome, growth hormone insensitivity syndromes. Although these
      conditions might be rare, their susceptibility to analysis was due largely to
      availability and progress of the molecular biological methods. The aim of this
      review article is to introduce the language of molecular biology by means of a
      selected group of endocrine disorders.

PMID- 8529706
TI  - Preventive and therapeutic AIDS peptide vaccines.

PMID- 8529709
TI  - Factors predicting the risk of relapse after antiepileptic drug discontinuation
      in children with partial seizures.
AB  - The purpose of this study is to identify possible factors which could influence
      the seizure recurrence after anti-epileptic drug (AED) withdrawal in children
      with partial epilepsy. AED was discontinued in 82 children who had been free of
      partial epileptic seizures for 2.0-11.0 years (mean 4.7 years). Twenty-four
      patients (29.3%) had a relapse from a few days to 6.1 years (mean 1.2 years)
      after AED discontinuation. Significantly more common in children who relapsed
      were: younger age at beginning of AED withdrawal, occurrence of complicated
      febrile convulsions (5/24 vs 1/58, P < 0.01), abnormal neurological examination
      (8/24 vs 8/58, P < 0.05), delayed psychomotor development (7/24 vs 7/58, P <
      0.05), focal slowing (6/24 vs 3/58, P < 0.01) and focal epilepti-form discharges
      (7/24 vs 6/58, P < 0.05) in the last EEG before AED discontinuation. Between the
      two groups no statistical significant differences concerning the age at onset of
      seizures, the duration at AED therapy after the last seizure, the familial
      occurrence of epilepsy and background EEG abnormalities in the last EEG before
      AED discontinuation were found. On the basis of EEG, occurrence of febrile
      convulsions, and neurological and developmental examination it may be possible to
      predict which children have the best chance to remain free of recurrence after
      AED discontinuation.

PMID- 8529710
TI  - Development of motion perception in early infancy.
AB  - This article summarizes some research on the development of motion perception in
      early infancy. The sensitivity for slow and rapid motion was studied with 1-month
      old and 3-month-old babies. The findings suggest that there are different
      developmental courses for the detection of slow and rapid motion. The ability to
      detect very slow motion seems to improve gradually with age whereas the
      sensitivity for very rapid motion seems to be at a level comparable to adults
      soon after birth. Three-month-old babies do use kinetic visual information in
      order to perceive object boundaries and form. After having seen a form visible
      only when moving they are able to "identify" the same form when seeing it under
      static conditions. Infants and young children do use kinetic visual information
      for recognizing figures that are never completely in sight only if they have been
      familiarized with the fully visible form first. Even 4-year-olds have
      difficulties in perceiving the full form of a figure that moves behind a slit in
      an opaque occluding surface if there is no familiarity or "priming" with the
      global form first. In conclusion, infants are able to detect visual motion very
      early in life and do extract information which leads to the perception of form.
      However, this ability may be limited to events with uninterrupted, continuous
      movement of visible elements.

PMID- 8529711
TI  - The curriculum vitae of Professor Ettore Rossi (on the occasion of his 80th
      birthday).

PMID- 8529714
TI  - Histological features of glomerular immaturity in infants and small children with
      normal or altered tubular function.
AB  - In children with renal tubular disorders the existence of retarded histological
      features of glomerular maturation has been suggested by our group. However, no
      valuable information is available on the frequency of histopathologically
      immature glomeruli in the normal kidney. For this reason we established a simple,
      semiquantitative definition of postnatal glomerular development: immature
      glomeruli (with at least half of the circumference of capillary loops densely
      lined with cuboidal epithelial cells), intermediate glomeruli (circumference of
      capillary loops lined with at least five adjoining cuboidal cells), and mature
      glomeruli. This definition was applied in a set of 71 normal kidneys from ages
      birth to 5 years. The relative frequency of the mentioned stages of glomerular
      maturation was strongly age dependent. In comparing the patients data with the
      normal findings it was possible to separate patients with the finding of
      disproportionately high fractions of immature glomeruli, provided the right age
      at biopsy is chosen. It is therefore concluded that the previous suspicion of
      late glomerular maturation may be validated in at least in some bioptic
      specimens.

PMID- 8529712
TI  - Mechanisms of bilirubin toxicity.
AB  - Possible mechanisms of bilirubin toxicity on the brain and lung were studied in
      animal experiments and in vitro. The uptake of tyrosine as precursor of dopamine
      in rat synaptosomes was evaluated to study the role of different bilirubin
      concentrations on synaptic neurotransmission. The results of this study show a
      statistically significant correlation between bilirubin levels and tyrosine
      uptake, supporting the hypothesis that the effect of bilirubin on neuronal
      excitability is dose-dependent. Concerning bilirubin toxicity on the lung, we
      studied the effect of different bilirubin concentrations on surface activity of
      modified natural surfactant (Curosurf) and synthetic surfactant (Exosurf), both
      in current clinical use for treatment of neonatal respiratory distress syndrome.
      Surface activity of Curosurf and Exosurf was investigated with the captive bubble
      surfactometer. The results of this study show that bilirubin impairs, in vitro,
      the surface tension activity of natural surfactant in a dose dependent manner and
      has no effect on surface tension activity of artificial surfactant. These data
      suggest that bilirubin interferes with surfactant proteins SP-B and/or SP-C, thus
      impairing surfactant activity at the air-liquid interface. We conclude that
      bilirubin shows its toxic effect reacting with different biological systems in a
      dose-dependent fashion.

PMID- 8529715
TI  - The age at onset of chronic Pseudomonas aeruginosa colonization in cystic
      fibrosis--prognostic significance.
AB  - To evaluate the prognostic significance of the age at onset of chronic
      Pseudomonas aeruginosa colonization (OPCP) with respect to pulmonary disease
      progression in patients with cystic fibrosis (CF), a retrospective long-term
      analysis using annual chest radiographs was performed on 54 CF patients. Thirty
      seven patients (68%) were chronically colonized before the age of 12 years (group
      1), 17 patients (32%) thereafter (group 2). These two groups did not
      significantly differ in terms of mean duration of follow up (16.2 +/- 5.9 years),
      sex, CF genotypes, colonization with other respiratory pathogens, supportive
      medical treatment and death rate during the study period. Chest radiographs were
      evaluated according to the Chrispin-Norman score, increasing scores representing
      increasing severity of respiratory disease. In both groups, progression of score
      means was not accelerated of score means was not accelerated up to 6 years after
      OCPC (Scores at OCPC set 0; mean score +/- SEM 6 years prior to OCPC -5.6 +/-
      2.0; 10 years after OCPC +3.6 +/- 0.7 points). Patients chronically colonized
      prior to age 12 years (group 1) scored significantly higher between age 2 and 11
      years (maximum difference at age 8 years [mean +/- SEM]: 9.4 +/- 0.7 vs. 4.3 +/-
      1.3 points; P = 0.002) as compared to group 2. After age 11 years, mean scores
      were similar in both groups, since in group 2 scores increased rapidly after age
      8 years. We conclude that OCPC did not cause an immediate acceleration of CF lung
      disease judged by serial chest radiographs. Rapid progression in group 2 (OCPC
      after age 12 years) was independent of OCPC since it occurred earlier. These data
      indicate that OCPC may be a marker rather than the cause of respiratory disease
      progression.

PMID- 8529713
TI  - Immunthrombocytopenic purpura as a model for pathogenesis and treatment of
      autoimmunity.
AB  - In honour of Professor Rossi's 80th birthday we review the development of our
      understanding of the immune and auto-immune nature of the pathogenesis of immune
      thrombocytopenic purpura (ITP). The immune aspects have been documented by
      postviral alterations of the cellular and humoral immune system, by new methods
      of specific auto-antibody detection against platelet glycoproteins and by the
      therapeutic effect of administering immunoglobulin concentrate from healthy blood
      donors. The various possible mechanisms of action of immunoglobulin treatment
      have led to use of this treatment as an alternative for other immune-related
      disorders. The treatment of severe chronic ITP in children, however, remains
      unsatisfactory. With a new international clinical and laboratory study of
      children and adolescents with early chronic ITP we are continuing the
      investigation of the pathogenesis and treatment of ITP.

PMID- 8529716
TI  - Mycobacterium genavense invasive infection in two children with AIDS: long-term
      followup.
AB  - Mycobacterium genavense is a rare cause of opportunistic infection in
      immunocompromised hosts. Follow up of two cases of M. genavense invasive
      infection in children with haemophilia A and AIDS are presented. One patient died
      18 months after diagnosis of M. genavense infection of an indirectly related
      cause, probably of Pneumocystis carinii pneumonia. The second patient still
      attends our outpatient clinic and the infection is under control. Both presented
      with abdominal lymphomas and pain and a wasting syndrome. A combination of
      several drugs against atypical mycobacteria is used for treatment.

PMID- 8529718
TI  - Adults with congenital heart disease--the important role and obligation of the
      paediatric cardiologist and the general paediatrician.

PMID- 8529717
TI  - Compliance with therapy in children with respiratory diseases.
AB  - Compliance with medical treatment was evaluated in 89 children and adolescents
      with respiratory diseases using two methods of assessment: a double blinded
      covert recording of the use of an air compressor for nebulization of drugs and
      the determination of theophylline levels in serum. In the covert monitoring of
      inhalation the overall compliance with the prescribed medication was 47.6%. In
      the open randomized theophylline trial, 56%-71% of the patients (according to
      uncontrolled or controlled intake of the drug) received a dosage of theophylline
      which was too low to achieve a sufficient serum level in the range of 10-20 mg/l.
      This, however, was also due to the fact that in 72% of the cases physicians
      prescribed doses which were substantially below the recommended amount of drug
      according to age and weight. It is, therefore, concluded that compliance of
      medication is based on the patients adherence to the medication, to the efficacy
      of the drug itself and the attitude of the physician.

PMID- 8529719
TI  - Psychosocial aspects in the treatment of children with myelomeningocele: an
      assessment after a decade.
AB  - The aim of this study was to recognize the possible psychological advantages when
      children with a severe CNS disorder like myelomeningocele (MMC) are given very
      early rehabilitation treatment. One hundred and seven newborns with MMC seen
      between 1971-1992 were prospectively analysed with respect to two different
      therapeutic approaches. The children born during the period 1971-1980 did not
      receive very early therapeutic rehabilitation treatment, whereas those born
      during the period 1981-1992, received this treatment. In the latter group,
      special attention was paid to support an improvement in the difficult
      relationship between the parents and the child with MMC as well as between
      parents and caregivers. The following statistically significant differences
      between the two treatment programmes were found: (1) all children achieved
      independent locomotion at 5 years, in the very early intervention group, compared
      to only 35% (P < 0.001) in the group without this programme. Orthopaedic
      operations in the first-mentioned group were markedly reduced; (2) urological
      surgery decreased drastically in the group with very early urodynamic
      rehabilitation. Thus, there were 0.6 operations per patient in the older group,
      but only 0.06 operations per patient in the younger one (P < 0.001); (3) normal
      schooling was reached by 76% (22/29) and social continence by 80% (23/29) of the
      children with very early interventional therapy. In the older group only 54%
      reached normal schooling (P < 0.05) and 29% social continence (P < 0.001). The
      very early co-ordinated medical and physiotherapeutic rehabilitation treatment of
      children with MMC usually reduces the psychosocial stress and improves the
      quality of life of these children and of their families.

PMID- 8529720
TI  - Advances in cystic fibrosis: bringing the bench to the bedside.

PMID- 8529722
TI  - Cerebral ischemia: from pharmacology to modern techniques and clinical
      implications. Value of almitrine-raubasin (Duxil Duxaril). International
      symposium, Hangzhou, People's Republic of China, May 14, 1994.

PMID- 8529721
TI  - Screening for retinopathy of prematurity after surfactant treatment.
AB  - Surfactant administration in premature infants is supposed to induce rapid
      changes in tissue oxygenation. It might therefore modify the risk of developing
      retinopathy of prematurity (ROP). We have been using the so-called safety index
      [equation see text] to calculate the number of infants at low risk to develop ROP
      stage 3 or higher (SI > or = 1) after administration of two preparations of a
      surfactant. The study population consisted of 255 prematures of < or = 2000 g
      birth weight treated with surfactant for respiratory distress syndrome in
      Switzerland between 1991 and 1993. Of these infants, 29 received a natural
      surfactant (Curosurf), and 226 infants were treated with the synthetic surfactant
      Exosurf. Reduction of fraction inspired oxygen (FiO2) was significant within 3
      and 6 h and was more pronounced in infants having received natural surfactant. An
      SI > or = 1 was calculated in 106 of the 226 infants (47%) treated with Exosurf.
      Only one of these infants developed ROP stage 3 in one eye (no ROP in the fellow
      eye) whereas 12 infants with ROP stages 3 or 4 had an SI < 1. Seven of the 29
      infants treated with natural surfactant had an SI > or = 1; none of these infants
      developed ROP > stage 2. According to this survey, the risk of developing severe
      stages of ROP does not increase in low birth weight infants who have been treated
      with surfactant. Irrespective of a surfactant therapy, the calculation of the SI
      is useful for substantially reducing the number of prematures who need intensive
      ophthalmological follow up.

PMID- 8529723
TI  - Glial fibrillary acidic protein expression after transient brain ischemia:
      evidence for a pharmacological modulation by almitrine-raubasine.

PMID- 8529724
TI  - Assessment of cerebrovascular disease with positron emission tomography: attempt
      of an in vivo model for treatment evaluation of brain glucose metabolism.

PMID- 8529725
TI  - Vascular pathology in the elderly.

PMID- 8529726
TI  - Pathophysiology of postischemic hypoxia and cerebral protection: implications of
      the almitrine and raubasine combination.

PMID- 8529727
TI  - Pharmacological strategies in the treatment of cerebral ischemia.

PMID- 8529728
TI  - Quantitative electroencephalography in aging brain and cerebrovascular disease:
      the effects of almitrine-raubasine.

PMID- 8529729
TI  - Memory disorders in 8,037 elderly patients with age-associated memory impairment:
      multicenter trial with a 6-month follow-up under almitrine-raubasine.

PMID- 8529730
TI  - Epidemiology of cerebrovascular disease in the People's Republic of China.

PMID- 8529731
TI  - Five-year results of neoadjuvant cisplatin, methotrexate and vinblastine
      chemotherapy plus radical cystectomy in locally advanced bladder cancer.
AB  - Neoadjuvant systemic cisplatin, methotrexate and vinblastine chemotherapy has
      been used in the treatment of 69 patients with advanced bladder cancer (stages T2
      T4 N+/N0 M0). Sixty patients were evaluable for response at a median follow-up of
      48 months. Preoperative resection of the tumor was purposely avoided in order to
      keep a marker lesion. After planned radical cystectomy, pathological complete
      responses (pCRs) and partial responses (pPRs) were documented in 5 (8.3%) and 29
      cases (43.4%), respectively. These patients had a 5-year disease-free survival
      rate of 80%, which was statistically superior (p = 0.0013) to 35% for the
      remaining nonresponding patients. One patient (20%) with a pCR died of systemic
      disease after 14 months, while the remaining 4 patients (80%) are alive and free
      of disease after a median follow-up of 57 months. A higher percentage of pCRs and
      pPRs was observed in the group of patients with stage T3b-T4 tumor (pCR 11%, pPR
      63%) in contrast to the patients with stage T2-T3a disease (pCR 4.5%, pPR 45.5%),
      even if no significant difference in the 5-year survival rate was observed
      between the 2 groups. Patients with a G2 tumor before chemotherapy survived
      longer (5-year survival rate of 78%) than those with G3 disease (5-year survival
      rate of 61%), but no significant difference was achieved.

PMID- 8529733
TI  - Failures and complications of transurethral ureteroscopy in 297 cases:
      conventional rigid instruments vs. small caliber semirigid ureteroscopes.
AB  - To evaluate the safety and effectiveness of ureteroscopic stone manipulation, we
      retrospectively reviewed the failure and complication rates of two series of
      retrograde ureteroscopies (URS) according to the instrument used: the
      conventional rigid ureteroscopes and the new fiberoptic small size ureteroscopes.
      From July 1985 to December 1992, we performed 248 URS in 238 patients using a
      conventional rigid ureteroscope. From January 1992 to December 1992, we performed
      49 URS in 47 patients using a semirigid ureteroscope. The failure rate was 14.5%
      in the first group of patients. The early and late complications observed were:
      urinary tract infections (UTI) in 22.5%, small mucosal lesions (false route) in
      24.5%, full-thickness perforations in 11.2%, migration of the stone fragments
      into the retroperitoneum in 0.4% and the rupture of the tip of an alligator
      forceps into the ureteral lumen in 0.4%. Ureteral stenosis was observed in 1.6%
      of the cases. Often two or more complications occurred in the same patient. In
      the second group the failure rate was 10.2% and the complication rate 8.1%. We
      reported one case of ureteral perforation (2%), 3 mucosal lesions (6.1%) and UTI
      in 2 cases (4%). We conclude that URS using a small-caliber semirigid
      ureteroscope is a safer procedure than URS with conventional instruments. The
      majority of failures with semirigid scopes is related to the laser
      ineffectiveness in fragmenting the stone.

PMID- 8529732
TI  - Oral diclofenac in the prophylactic treatment of recurrent renal colic. A double
      blind comparison with placebo.
AB  - We have conducted a double-blind, randomized, placebo-controlled trial with oral
      diclofenac to study the prophylactic effect on renal colic recurrence and
      spontaneous stone expulsion rate. Forty-one patients were given 50 mg oral
      diclofenac 3 times a day for 7 days after being discharged for a colic episode
      from Oslo Emergency Hospital (< 24 h stay) and 39 patients were given matching
      placebo tablets. The number of new renal colic episodes per accumulated patient
      treatment days was 64/287 in the diclofenac group and 119/273 in the placebo
      group (p < 0.01). This difference was greatest during the first 4 treatment days.
      A similar trend was found for pain intensity (0-10 cm VAS) with the greatest
      difference on day 1 (4.3 vs. 2.8, p = 0.05). Side effects, mainly
      gastrointestinal, were reported for 14% of the treatment days in both treatment
      groups. Stone expulsion rate was almost identical (28 vs. 29 days), regardless of
      stone size. Readmission rate to Oslo Emergency Hospital/other hospitals were 10
      and 67% (p < 0.001). In conclusion, oral treatment with diclofenac was effective
      as short-term prophylaxis of new colic episodes, especially during the first 4
      days, and reduces the number of hospital readmissions significantly. The stone
      passage rate appears not to be affected.

PMID- 8529735
TI  - Successful treatment of postretroperitoneal lymph node dissection in massive
      chylous ascites.
AB  - A rare complication of retroperitoneal surgery is damage to lymphatic vessels,
      leak of chyle and the development of chylous ascites. This complication can be
      life threatening and has a relatively high mortality rate. We describe a 38-year
      old patient with a massive chylous ascites after extensive retroperitoneal lymph
      node dissection of metastatic nonseminomatous germ cell testicular tumor. The
      patient was treated surgically and with fat-free diet, medium chain triglycerides
      and diuretics resulting in complete resolution of the ascites.

PMID- 8529734
TI  - Bilateral simultaneous percutaneous nephrolithotomy. A prospective feasibility
      study.
AB  - A prospective study was undertaken to assess the feasibility and safety of
      bilateral simultaneous percutaneous nephrolithotomy (BPNL) under single
      anesthesia. BPNL was attempted in 16 consecutive patients with upper tract
      urolithiasis suitable for percutaneous treatment bilaterally. Bilateral
      simultaneous PNL could be accomplished in 14 of 16 cases; the opposite side was
      abandoned in 2 due to technical reasons. The operating sides could be switched
      within a short period (15 min) by rotating the patient table by 180 degrees. The
      average total operating time and irrigation time was 83 and 43 min, respectively.
      A total of 29 tracts and 18 sessions were required for endourologic treatment of
      28 units in 14 patients. There was no significant morbidity. Complete clearance
      was achieved in 11 of 14 patients; there was insignificant residue in 1, while 2
      with major residue required adjunct JJ stenting and extra-corporeal shockwave
      lithotripsy. The average hospital stay was 5.4 days. After initial proficiency
      with endourology, preparedness for BPNL is advisable in all such cases.

PMID- 8529736
TI  - Noncalculous obstruction due to involvement of the ureter in endometriosis.
AB  - A retrospective case series of 5 consecutive patients presenting with
      endometriosis of the ureter between 1978 and 1992 is reported. All patients were
      managed by a single Consultant Urologist in a district general hospital. The mean
      age of patients was 40.4 years (34-45). Only 1 patient had symptomatic ureteric
      obstruction. In 4 patients the diagnosis was incidental. Preservation or salvage
      of renal function will usually require surgical intervention. The diagnosis
      should be considered in women presenting with noncalculous ureteric obstruction,
      particularly premenopausal women of low parity or those who have had previously
      pelvic surgery. The pathology, presentation, investigation and management of the
      condition is discussed.

PMID- 8529737
TI  - Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation
      resistant to psychotherapy.
AB  - alpha 1-Blocking agents (alphuzosine and terazosine) have been tested to
      determine their effectiveness over a placebo in the treatment of premature
      ejaculation. A total of 91 patients, all of whom were resistant to psychological
      therapy, were submitted to a double-blind controlled cross-over trial. Side
      effects were recorded as well. Alphuzosine and terazosine proved effective in
      approximately 50% of the cases and were, thus, significantly more active than the
      placebo; moreover no significant difference was found between them in terms of
      side effects. It is concluded that alpha 1 blockers are reasonably safe active
      drugs, effective in the treatment of premature ejaculation which does not respond
      to the psychological approach.

PMID- 8529738
TI  - Ferritin: a tumor marker expressed by renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) has been shown to secrete several hormones and
      biologically active substances that influence the host metabolism or induce
      paraneoplastic syndromes. Observation of anemia in 20% of patients with RCC and
      the spontaneous recovery of anemia following nephrectomy drew attention to the
      body iron metabolism. Ferritin was previously proposed as a tumor marker for RCC.
      In order to determine whether RCC cells actually produce ferritin, we studied
      ferritin levels in serum from peripheral and renal veins as well as from the
      tumor tissue and the healthy parenchyma from radical nephrectomy specimens of 22
      patients with RCC. Ferritin levels both in sera and cytosols were measured by an
      enzyme immunoassay method. The mean serum ferritin level from the renal vein was
      419.9 +/- 72.4 ng/ml, and it was 157.3 +/- 18.3 ng/ml from the peripheral vein (p
      < 0.05). Renal vein ferritin correlated with stage and had a significant impact
      on prognosis (p < 0.05). The mean cytosolic ferritin level of the cancer tissue
      was 705.6 +/- 56.9 ng/mg cytosol protein, whereas in the normal parenchyma it was
      95.9 +/- 10.1 ng/mg cytosol protein. This was also highly significant (p = 1.15 x
      10(-13)), suggesting that RCC cells probably express ferritin. As currently there
      exists no reliable tumor marker for RCC, the value of ferritin as a marker should
      be investigated further before drawing any clinical conclusions.

PMID- 8529739
TI  - p53 and Rb immunostaining in locally advanced bladder cancer: relation to
      prognostic variables and predictive value for the local response to radical
      radiotherapy.
AB  - The association between known prognostic variables and altered immunostaining for
      the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous
      series of locally advanced bladder cancer. The predictive value of this
      immunostaining for the local response to intended radical radiotherapy was
      investigated. Among 262 patients treated with intended radical radiotherapy
      between 1967 and 1986, a total of 154 patients were evaluable with respect to
      local response to treatment. The paraffin-embedded specimen from the tumour prior
      to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb
      and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at
      650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the
      tumours, respectively. p53 overexpression was associated with higher tumour
      grade. However, the results of the p53 and Rb immunostaining procedures had no
      predictive value for tumor response to radiation treatment, local control or
      cancer-specific mortality.

PMID- 8529740
TI  - Is ipsilateral testis mandatory for the occurrence of contralateral
      intratesticular biochemical changes indicative of hypoxia after unilateral
      spermatic cord torsion?
AB  - Experimental unilateral spermatic cord torsion has been shown to induce both
      ipsilateral and contralateral intratesticular biochemical changes indicative of
      hypoxia. An experimental study was conducted to see whether the presence of the
      ipsilateral testicular tissue is necessary for the occurrence of the biochemical
      changes in the contralateral testis. Male, adult, albino rats were divided into
      four groups each containing 10 rats. One group served to determine basal values
      of biochemical parameters indicative of tissue hypoxia, another group was
      subjected to unilateral spermatic cord torsion in the presence of ipsilateral
      testis; a further group was subjected to unilateral spermatic cord torsion after
      ipsilateral subepididymal orchiectomy, and the last group underwent unilateral
      subepididymal orchiectomy alone as control. Lactic acid, hypoxanthine and lipid
      peroxidation product levels which are biochemical indicators of tissue hypoxia
      were determined in testicular tissues and kidneys. All three parameters increased
      significantly in contralateral testes but not in kidneys after unilateral
      spermatic cord torsion both when the ipsilateral testis was present and absent (p
      < 0.05). It is concluded that the ipsilateral testis does not play a role in
      transmitting these contralateral changes after unilateral spermatic cord torsion.
      Impulse-triggering contralateral changes may arise from spermatic vessels or
      nerves.

PMID- 8529741
TI  - Subsequent biological effects of chemical sympathectomy in rats undergoing
      unilateral testicular torsion.
AB  - The effects of chemical sympathectomy on contralateral testicular histology,
      fertility and fecundity following unilateral testicular torsion were evaluated in
      rats. Four groups, placebo plus sham operation, 6-OH-dopamine plus sham
      operation, placebo plus torsion, and 6-OH-dopamine plus torsion, were
      established. When the placebo plus sham operation and placebo plus torsion groups
      were compared, it was found that contralateral testicular damage following
      unilateral testicular torsion occurred with significantly decreased values for
      mean seminiferous tubular diameter (MSTD), mean testicular biopsy score (MTBS)
      and fertility. The relatively normal values for MSTD, MTBS and fertility in the 6
      OH-dopamine plus sham operation and 6-OH-dopamine plus torsion groups indicate
      the preventive role of chemical sympathectomy on contralateral testicular damage.
      Since chemical sympathectomy prevents contralateral histologic deterioration and
      preserves fertility in unilateral testicular torsion, the decreased blood flow in
      the reflex-activating sympathetic system may play a role in contralateral
      testicular damage.

PMID- 8529742
TI  - Flow cytometric DNA studies and AgNOR counts in patients with transitional cell
      carcinoma of the bladder.
AB  - Flow cytometry appears to be a promising diagnostic method which may influence
      the therapeutic approach to transitional cell carcinoma (TCC) of the bladder. The
      number of silver-stained nuclear organizer regions (AgNORs) seems to correlate
      with the growth fractions of the cells. In this study, we report the results of
      combined flow cytometric analysis and AgNOR in 37 patients with TCC of the
      bladder. A positive correlation was observed in the histological grade, stage and
      growth pattern in relation to the ploidy of tumors. There were statistically
      significant differences among the mean AgNOR counts of the different groups as
      defined by DNA content, histological grade, growth pattern and disease outcome.
      In different stage groups, the AgNOR counts were related both to recurrence and
      progression. It was concluded that AgNOR counts performed on routine formalin
      fixed paraffin sections furnish significant kinetic information. According to our
      preliminary results AgNOR counts and the DNA content of the tumors should also be
      measured to decide on more aggressive treatment in some cases.

PMID- 8529743
TI  - Pediatric urology and the daily medical practice: way apart?
AB  - This is a study about the current status of knowledge and level of insight in
      treatment possibilities of pediatric urological diseases in daily practice of
      Dutch general practitioners (GPs). A questionnaire was mailed to GPs with
      questions concerning the structure of their medical practice, the localization,
      the received education in pediatric urology and knowledge of this subspeciality.
      Also, questions were asked about their current knowledge and first choice of
      treatment for maldescensus testis, urinary tract infections, enuresis nocturna
      and congenital abnormalities. The 995 forms that were returned, representing
      1,457 GPs, are discussed. New developments in diagnostic procedures and treatment
      possibilities should be reflected in the exchange of information between GPs and
      (sub)specialists. However, before changes can be realized, the current knowledge
      and opinions should be known. This study investigates the current opinion of GPs
      of different pediatric urological diseases. Additionally, the incidence and
      current state of the art in diagnosis and treatment are discussed.

PMID- 8529744
TI  - Social and medical aspects of undescended testes in Turkey.
AB  - In this study, 6,381 primary school boys were examined in Turkey in the years
      1990 and 1991 and families and medical personnel were questioned about the
      information they had on undescended testes and their behavior regarding this
      matter was noted. Undescended testes were found in 91/6,381 pupils (1.43%) Forty
      six families (58.7%) were aware of the abnormality. In 36 of these 46 cases
      (78%), the mother was the first who noticed the problem. Only 3 cases were first
      diagnosed by medical staff (nurses or doctors). Eighteen cases were diagnosed
      under 2 years of age, but apparently they had not been managed correctly because
      of ignorance regarding possible complications. Of the 46 families, who were aware
      of the problem, only 29 (63%) had seen a physician. In other words, only 31%
      (29/91) of the boys with undescended testes received medical help. This study has
      shown that no genital organ examination of the newborn is performed after most
      deliveries and there is a considerable unawareness of undescended testes both by
      the families and by medical personnel.

PMID- 8529745
TI  - Patterns of integration and clinical value of voiding cystourethrography in the
      work-up of urinary tract infection in children.
AB  - OBJECTIVE: To evaluate the patterns of integration and the clinical value of
      voiding cystourethrography (VCUG) in the imaging work-up of children with urinary
      tract infection (UTI). METHODS: We reviewed the medical records of a consecutive
      sample of 80 children that underwent VCUG as part of routine investigation for
      UTI. We assessed the following: the appropriateness of integration of VCUG in the
      patient work-up as determined by the presence or absence of a valid indication
      for VCUG in the specific clinical situation encountered, the correct timing of
      the examination and interpretation of its result; the change in clinical
      management initiated by the result of the test, and the reassurance conferred to
      the clinician. RESULTS: Sixty-nine percent of the VCUG examinations were judged
      appropriately integrated, 14% of the examinations inappropriately integrated,
      while for the rest of the patients (17%) the appropriateness of integration of
      the test was rated as unclear. The change in patient management attributable to
      the VCUG result could be categorized as: no change (15%); decision to end the
      imaging investigation of the patient (39%); decision to end all investigations,
      and prophylactic or therapeutic interventions (17%); decision to discontinue
      chemoprophylaxis (1%); decision to end the imaging investigation and introduce
      chemoprophylaxis and follow-up for bacteriuria (5%); decision to continue the
      imaging investigation and introduce chemoprophylaxis and follow-up for
      bacteriuria (15%), and decision to operate or help in planning the surgical
      treatment required (8%). CONCLUSION: The findings show the need for an increased
      effort to minimize overuse of VCUG in pediatric UTI. Future interventions should
      focus on issues of clinical efficacy of the method that may have not been
      emphasized sufficiently.

PMID- 8529746
TI  - Transurethral laser surgery with a conventional modified resectoscope.
AB  - A new 1,800-microns side fiber made of pure silica with laser beam deviation of
      82 degrees and divergence of 18 degrees was inserted into a modified
      transurethral resectoscope and used to treat in vitro some prostates removed
      during radical prostatectomy. Sterilization of prostatic tissue with a depth of
      penetration of 12 mm was observed after treatment with 20 W for 2 min.
      Irradiation with 60 W for 1 min produced vaporization and explosion of the tissue
      and a depth of penetration of 15 mm. The laser resectoscope was then successfully
      employed for the treatment of 6 cases of benign prostatic hyperplasia (BPH) as
      well as in high risk patients with bulky bleeding bladder tumors (4 cases) and
      with transitional carcinoma of the prostate invading the parenchyma (2 cases). 3
      patients with small size BPH underwent only laser irradiation. All others were
      submitted to traditional transurethral resection followed by laser treatment with
      Nd: YAG using the same instrument. Our laser resectoscope lowers costs since the
      side fiber is reusable for 4-5 treatments and brings laser treatment nearer to
      traditional endoscopic treatment, thereby making its application more comfortable
      for the urologist.

PMID- 8529748
TI  - Current controversies in the management of localized prostate cancer.
AB  - As longevity has improved and mortality from cardiovascular and other diseases
      has declined, the risk of death from prostate cancer has increased steadily.
      Though slow growing, prostate cancer is not a benign disease. Nearly 10% of men
      in Western countries will be diagnosed with prostate cancer sometime during their
      life and 3% will die of the disease. The prospects for long-term control of
      prostate cancer diminish rapidly once the cancer has spread beyond the immediate
      periprostatic tissue. The 5-year survival rate for men with metastases is less
      than 30% and almost all will eventually die of their disease. A simple blood
      test, prostate-specific antigen (PSA), is available. This test, when used in
      conjunction with ultrasound-guided systematic needle biopsy of the prostate, will
      detect potentially lethal prostate cancers earlier than digital rectal
      examination (DRE). Definitive treatment, especially with radical prostatectomy,
      can eradicate the tumor in 90% of patients if the cancer is still confined to the
      prostate pathologically, regardless of the tumor grade. Randomized, prospective
      clinical trials are now underway to demonstrate conclusively whether screening or
      early definitive therapy will substantially reduce the mortality rate from this
      disease. Until the results of these trials are available, we recommend that
      healthy men over age 50, who have a life expectancy of 10 years or longer, have
      an annual PSA and DRE to detect prostate cancer while it is still curable.

PMID- 8529747
TI  - Ureteral endometriosis in a female patient presenting with single-kidney anuria.
AB  - Endometriosis affecting the urinary tract is very rare. We report on a female
      patient with a single kidney who presented with anuria due to ureteral
      endometriosis. Initially a limited ureterectomy with an end-to-end anastomosis
      was performed. After removing the stent, endometriosis recurred. On
      reexploration, the terminal ureter was removed and the sound end reimplanted into
      the urinary bladder. A salpingo-oophorectomy was performed, and danazol 400 mg
      twice daily was started, with very satisfactory results. Endometriosis on a
      single acquired ureter causing anuria has, to our knowledge, not been reported
      previously. The modality of treatment is local excision, oophorectomy, and
      danazol.

PMID- 8529749
TI  - Dentofacial growth in orthodontically treated and untreated children with
      juvenile chronic arthritis (JCA). A comparison with Angle Class II division 1
      subjects.
AB  - The changes in craniofacial growth and development of dental occlusion were
      studied in children with juvenile chronic arthritis (JCA), and treatment with
      functional orthodontic appliances (activators) was tested in both JCA and healthy
      children with distal occlusion. Fifteen JCA children with Angle Class I occlusion
      and 15 JCA children with Angle Class II malocclusion were followed longitudinally
      and compared with 23 healthy children with Angle Class II malocclusion. The
      facial growth of the JCA children without need of orthodontic treatment mainly
      followed the normal pattern while the JCA children with Angle Class II
      malocclusion had a deviating facial morphology, which became more abnormal during
      growth. During the orthodontic treatment period a slight improvement was seen in
      mandibular positions in the sagittal and vertical planes in both treated groups,
      but the changes were more marked in the healthy children. None of the treated
      groups attained completely normal facial morphology, but in most children the
      occlusion improved and could be classified as normal. The morphology achieved by
      treatment largely remained the same during the follow-up period and relapse was
      seen only in a few children. JCA children with minor skeletal discrepancies can
      be satisfactorily treated during growth with functional orthodontic appliances,
      possibly in combination with fixed appliances. Even if skeletal changes in
      response to orthodontic treatment are rather limited, these changes combined with
      the improvement in dental occlusion obtained through treatment may result in
      better dentofacial aesthetics. Furthermore, jaw functions are likely to improve
      which also might benefit the patient from a psychosocial point of view.

PMID- 8529750
TI  - A cephalometric investigation of the effects of the Elastic Bite-block in the
      treatment of Class II division 1 malocclusions.
AB  - The purpose of this study was to investigate cephalometrically, the effects of a
      functional appliance-headgear combination, the Elastic Bite-block (EBB). Of 50
      Class II division 1 subjects who participated in this study, 30 made up the
      treatment group and 20 the control group. All of the selected cases exhibited
      mandibular retrognathism, facial growth pattern either along the Y-axis or in the
      horizontal direction, and were all at the peak of the prepubertal growth spurt.
      Whilst the EBB was applied to the treatment group for 1 year, no treatment was
      performed on the control group. Measurements made on the lateral cephalograms,
      obtained at the beginning and end of the study were statistically evaluated. The
      following changes took place as a result of EBB treatment: sagittal growth of the
      maxilla was inhibited, the upper molars were distalized and intruded, sagittal
      growth of the mandible was stimulated and the lower molars erupted in a mesio
      occlusal direction. As a result of downward and backward rotation of the
      mandible, the vertical dimension showed incremental changes. The upper and the
      lower incisors were both uprighted and intruded, and overjet and overbite
      decreased.

PMID- 8529752
TI  - Properties of superelastic wires and their relevance to orthodontic treatment.
AB  - In this study tools were developed to test and compare levelling archwires that
      the manufacturers claim to have superelastic properties. As the classic spring
      model and Hook's law cannot be applied, new parameters had to be found. It could
      be shown that three parameters are necessary to describe a superelastic archwire
      adequately: the distinctiveness of the pseudo-elastic plateau, the deflection at
      the beginning of the plateau, and the force level of the plateau. The results
      showed that many materials either did not show any pseudoelastic properties at
      all or that the wire parameters were such that they did not give any advantage
      over conventional work hardened NiTi materials. In many archwires the beginning
      of the plateau and thereby the desired characteristics began only when the
      archwire was displaced 1 mm or more. For many archwires the force level of this
      plateau also proved to be rather high with values often above 500 g.

PMID- 8529751
TI  - Condylar condition and mandibular growth during early functional treatment of
      children with juvenile chronic arthritis.
AB  - TMJ involvement in children with Juvenile Chronic Arthritis (JCA) will frequently
      cause disturbance of the growth of the mandible. Orthodontic treatment of these
      patients often includes orthognathic surgery, and are complicated to handle with
      respect to the damaged joint and impaired function. The aim of this presentation
      is to suggest an early treatment with a functional splint appliance, a
      distraction splint, with the purpose of increasing function of the joint and
      ensuring continuous growth of the mandible.

PMID- 8529753
TI  - Relationship between cranial base and maxillofacial morphology.
AB  - The aims of this study were to investigate the relationships between the cranial
      base and maxillofacial morphology in Japanese crania, and to examine the
      differences between Class I and Class II samples. Data were obtained from 46 male
      Japanese crania from the collection of the Jikei University School of Medicine
      (Tokyo). The sample represents populations which would have lived during the last
      100 years. A principal component analysis of linear and angular measurements
      showed that the anterior and posterior cranial base, and the cranial base angle
      were associated in different ways with different aspects of maxillofacial
      morphology. Variation in the anterior cranial base was associated with
      differences in facial height, lower facial height, bicondylar breadth, ramal
      height, and ramal width, while posterior cranial base length was correlated with
      bizygomatic breadth. The cranial base angle was negatively correlated with SNA (r
      = -0.46) and SNB (r = -0.59), and positively correlated with the palatal and
      occlusal plane angles. There were significant differences between Class I and
      Class II specimens in palatal width, SNA, ANB, and the palatal plane angle, but
      no significant difference in cranial base length or angle. The evidence suggested
      that cranial base shape and size was related to facial length, inclination of the
      maxilla, and both maxillary and mandibular prognathism.

PMID- 8529754
TI  - Electromagnetic articulography as a method for detecting the influence of spikes
      on tongue movement.
AB  - In orthodontics dysfunctions of the tongue are discussed as a factor in the
      development of malocclusion. A new objective method for examining tongue movement
      is the electromagnetic articulography (EMA). This enables movements of the tongue
      to be followed using the principle of inductive distance measurements. A helmet
      made of acrylic material serves as a carrier for three transmitter coils. These
      are located in front of the forehead, in front of the chin, and at the back of
      the neck. Receiver coils are fixed to the tip of the tongue and at two points on
      the dorsum of the tongue. The distance between the receiver and the transmitter
      coils is calculated by means of a personal computer. The movement trajectories
      are displayed on a computer screen in x-y-coordinates. Tongue movements of one
      patient with an anterior open bite are shown during characteristic test sounds
      and during swallowing. The first examination took place without any orthodontic
      appliance. In a second series in the same session, tongue movement was recorded
      under the influence of an orthodontic appliance with spikes. While the patient
      shows vertical combined with sagittal components in the movement pattern of the
      tongue without an orthodontic appliance, the same patient, under the influence of
      an orthodontic appliance with spikes, shows a change of the rest and work
      position of the tongue and in the pattern of tongue movement with a more
      posterior position of the tongue, and with an increase in the vertical and a
      decrease in the sagittal components of the movement pattern.

PMID- 8529755
TI  - Notes on the use of invertebrates, especially ciliates, in studies on pollution
      and toxicity.
AB  - After treatment of the paramecia with 0.0005% cartap solution a high mortality of
      the paramecia in the postautogamic experimental group was observed. In the
      studied postautogamic experimental daily isolation line some defective paramecia
      were found. The abnormality was manifested by a defective separation of animals
      during binary fission resulting in the formation of chain forms.

PMID- 8529757
TI  - Regulation of hepatic glucose production in healthy subjects and patients with
      non-insulin-dependent diabetes mellitus.
AB  - The regulation of endogenous glucose production is central to the control of
      blood glucose concentrations. In non-insulin-dependent diabetes mellitus (NIDDM),
      increased endogenous glucose production contributes to fasting hyperglycaemia.
      Gluconeogenesis appears to be exaggerated in NIDDM, and it may be hypothesized
      that an enhanced release of gluconeogenic precursors is responsible for increased
      total glucose output. However, it would appear that substrate-induced stimulation
      of gluconeogenesis fails to increase total glucose production in healthy humans
      and NIDDM patients. This autoregulation of endogenous glucose production may be
      attained by inhibition of glycogenolysis and/or gluconeogenesis from endogenous
      substrate. It has also been observed that stimulation of intrahepatic disposal of
      neoformed glucose (mainly as glycogen synthesis) contributes to autoregulation.
      These observations support the concept that intrahepatic disposal of glucose-6
      phosphate plays a major role in the control of endogenous glucose production.

PMID- 8529756
TI  - Third genetic polymorphism of tear proteins Rtp-3 in the rat.
AB  - Two genetic markers, tear proteins RTP-1 and RTP-2, were studied in six inbred
      rat strains by the agarose gel electrophoretic method. An RTP-2A fast migrating
      band was found in M520/W, AUG/W, and BN/Han W strains whereas in WAG/W, L-E/W and
      SPRD/W rats no RTP-2 band was detectable (Rtp-2b). In the case of RTP-1 there
      always occurred only one band but with a different migration speed in gel
      according to the representing allele. The slow band RTP-1B was observed in rat
      strains WAG/W, AUG/W, SPRD/W, L-E/W, and M520/W, the fast band RTP-1A being
      observed only in BN/HanW rats. Moreover, a considerable sex difference in the
      expression of tear protein in all the tested strains was observed. The expression
      of a third independent rat tear protein locus whose product, controlled by
      androgens, was found to be present only in females and castrated males. It is
      proposed to designate it Rtp-3 with three alleles: Rtp-3a, Rtp-3b, and Rtp-3c.
      The discrepancy of these results with the observation by Kondo et al. concerning
      Rtp-1 alleles has been discussed.

PMID- 8529758
TI  - Doubly labelled water measurement of total energy expenditure.
AB  - The doubly labelled water method uses the principles of indirect calorimetry to
      measure total energy expenditure from the turnover rates of two stable isotopes:
      deuterium and oxygen 18. Labelling total body water also provides estimates of
      body composition and measurements of water outflow rates. Although the principle
      of the method was determined in the 1950s, it was only applied to humans in the
      1980s. Some 15 years later, it is time for an objective appraisal of the method.
      This review first describes the principle and practice of the doubly labelled
      water method. The original concept described by Lifson and MacClintock is then
      discussed, and proposals are made to adapt the method to physiological and
      pathophysiological situations.

PMID- 8529759
TI  - Influence of ozone on haemoglobin oxygen affinity in type-2 diabetic patients
      with peripheral vascular disease: in vitro studies.
AB  - The use of ozone in the treatment of peripheral vascular disease (PVD) is
      increasing. The purpose of this study was to evaluate the effect of ozone on
      haemoglobin oxygen affinity in Type-2 diabetic patients with PVD. Twenty diabetic
      patients presenting with PVD (Clinical stage II-IV according to Fontaine) and 20
      non-diabetic healthy matched subjects were studied. In both groups, aliquots of
      blood were ozonised with mixtures of oxygen-ozone (O2-O3) to reach end
      concentrations of 6.5, 13, 26 and 78 micrograms O3 per ml of substrate. At
      baseline, diabetic patients presented significantly lower haemoglobin oxygen
      affinity values but higher plasma levels of free haemoglobin and
      malonyldialdehyde (MDA) than controls. In both diabetic patients and controls,
      exposure of blood to ozone reduced haemoglobin oxygen affinity in an "all-or
      none" fashion, without changing 2-3, diphosphoglycerate concentrations in
      erythrocytes. Both free haemoglobin and MDA concentrations showed significant,
      dose-dependent increases after blood ozonisation. Thus, ozone caused a
      significant increase in oxygen unloading of haemoglobin in both normal subjects
      and Type-2 diabetic patients with PVD.

PMID- 8529760
TI  - Comparison between acarbose, metformin, and insulin treatment in type 2 diabetic
      patients with secondary failure to sulfonylurea treatment.
AB  - The purpose of this study was to determine the most suitable treatment for Type 2
      (non-insulin-dependent) diabetic patients with secondary failure to sulfonylureas
      (SFS). In a four-month comparative study, 36 Type 2 diabetic patients given SFS
      were allocated to three treatment groups: A (n = 12, M/F 6/6, HbAlc 9.1 +/- 1.6%)
      received 0.3 IU/Kg body weight (BW) of insulin-Zn between 10 and 11 p.m.; B (n =
      12, M/F 6/6, HbAlc 9.2 +/- 1.6%) SFS plus 850 mg/day of metformin; and C (n = 12,
      M/F 6/6, HbAlc 9.5 +/- 2.4%) SFS plus acarbose 3 x 100 mg daily. Modifications in
      HbAlc, BW, blood pressure (BP), lipoprotein profile and insulin sensitivity were
      evaluated. HbAlc decreased in the three groups (A: 17.9 +/- 13.5%; B: 18.2 +/-
      4.5%; C: 7.6 +/- 16.8%; all p < 0.05; A and B vs C = p < 0.05). BW increased in
      group A and decreased in the other groups. BP decreased statistically in group B.
      HDL-cholesterol increased (1.26 +/- 0.46 vs 1.49 +/- 0.36 mmol/L; p < 0.05) and
      triglyceride levels decreased (1.68 +/- 0.85 vs 1.16 +/- 0.43 mmol/L; p < 0.05)
      in group A. There were no significant changes in the other studied parameters. We
      conclude that, for Type 2 diabetic patients given SFS, both insulin and metformin
      plus SFS provided better glycaemic control than acarbose plus SFS. Metformin
      combined with SFS offered further advantages for the control of BW and BP.

PMID- 8529761
TI  - Dietary protection against diabetes in NOD mice: lack of a major change in the
      immune system.
AB  - Pregestimil, a hypoallergenic infant formula in which casein hydrolysate replaces
      protein, protects NOD mice against diabetes, a T-cell-mediated autoimmune
      disease. Female and cyclosphosphamide (Cy)-treated male NOD mice were used to
      assess whether a modification of cellular immune mechanisms occurred when animals
      were fed Pregestimil from weaning to 110 days of life. Insulitis, sialitis and
      thyroiditis were observed, and the splenic T-cell proliferative response was
      measured. The ability of splenic T-cells of NOD mice in the Pregestimil group to
      transfer diabetes adoptively to young irradiated male NOD mice was also assessed.
      Pregestimil protected female NOD mice against spontaneous diabetes and male NOD
      mice against acute Cy-induced diabetes. Addition of bovine serum albumin (10%) to
      the diet did not alter the preventive effect. The Pregestimil diet also lessened
      insulitis severity in Cy-treated males, though not in females. Sialitis and
      thyroiditis, observed mainly in females, were not modified by the diets. The TCR
      mediated proliferative response of splenocytes tended to increase specifically in
      Pregestimil-fed and Cy-treated males. Sensitivity to IL-2 was improved. In
      females, the TCR-mediated proliferative response and the ability of T cells to
      transfer diabetes adoptively were unchanged. It is concluded that the protective
      effect of Pregestimil against diabetes in NOD mice cannot be explained by major
      changes in peripheral immune response.

PMID- 8529762
TI  - Inhibitory effect of amylin (islet amyloid polypeptide) on insulin response to
      non-glucose stimuli. Study in perfused rat pancreas.
AB  - Amylin, also called islet amyloid polypeptide (IAPP), can inhibit the glucose
      induced insulin secretion in perfused rat pancreas at 75 pmol/l, a concentration
      comparable to that found in the effluent of this experimental model. To further
      explore the influence of amylin on insulin release, we investigated the effect of
      synthetic rat amylin (75 pmol/l) on insulin response to non-glucose
      secretagogues. These agents stimulate B-cell secretion via different mechanisms,
      such as a dihydropyridine derivative (BAY K 8644, 10 mmol/l) which activates
      Ca(2+)-channels, a sulfonylurea (tolbutamide, 0.2 mmol/l) which blocks ATP
      dependent K(+)-channels, KCL (11 mmol/l) which depolarizes B cells and the 26-33
      fragment of cholecystokinin (8-CCK, 1 nmol/l) which increases phospholipid
      turnover. The study was performed in perfused rat pancreas. Amylin significantly
      inhibited insulin response to BAY K 8644 (65%), KCI (60%) and 8-CCK (80%) as well
      as the early phase of tolbutamide-induced insulin output (70%). Thus, amylin can
      inhibit insulin release induced by secretagogues that interact at different
      levels of B-cell stimulus-secretion coupling. This inhibition may be due to a
      multifarious influence of amylin on the B-cell secretory mechanism and/or a
      disturbing effect on a distal, crucial step in the insulin-releasing mechanism,
      e.g. by affecting exocytosis of the secretory granule or by inhibiting an
      essential metabolic pathway within the B cell.

PMID- 8529763
TI  - Changes in insulin receptor tyrosine kinase activity associated with metformin
      treatment of type 2 diabetes.
AB  - This study was performed to define the effect of metformin on glycaemic control
      and erythrocyte insulin receptor tyrosine kinase activity in patients with non
      insulin-dependent (Type 2) diabetes mellitus. A case-control study of the effect
      of metformin treatment in hyperglycaemic patients with Type 2 diabetes was
      conducted in outpatients of the Diabetes Clinical Center. The study population
      consisted of 14 patients with Type 2 diabetes (5 males, 9 females) whose
      hyperglycaemia was uncontrolled by diet. Patients were treated with metformin 850
      mg twice daily for 2 1/2 months. Fasting plasma glucose concentrations decreased
      from 8.9 to 6.4 mmol/L after 10 weeks of metformin treatment (p < 0.001), in
      association with significantly lower (p < 0.001) plasma glucose and insulin
      concentrations in response to an oral glucose load. In addition, both fasting
      plasma triglyceride and cholesterol concentrations were significantly (p < 0.001)
      lower after metformin treatment. There was no change in erythrocyte insulin
      receptor binding associated with metformin treatment, but both basal and insulin
      stimulated insulin receptor tyrosine kinase activities of solubilized erythrocyte
      insulin receptors were significantly higher after 10 weeks of metformin
      treatment. It is concluded that the increase in insulin-stimulated tyrosine
      kinase activity contributed to the improvement in glucose insulin and lipoprotein
      metabolism associated with metformin treatment of Type 2 diabetes.

PMID- 8529764
TI  - Low-cost measurement of body composition with 18O-enriched water.
AB  - Total body water (TBW) and body composition are crucial for the estimation of
      nutritional status in many clinical circumstances. While the measurement of TBW
      with 18O-enriched water is technically easier than with 2H2O, the cost of 10% 18O
      enriched water can be regarded as prohibitive. The aim of this study was to prove
      that less enriched (i.e. 2%) and cheaper (about 25 ECU per dose per subject, i.e.
      $30) 18O water can be used to measure TBW. In the 41 subjects studied, isotopic
      equilibrium was achieved 4 hours after the isotope was administered. Plateau
      enrichments in urine, saliva, and plasma samples did not differ significantly
      between 5 and 8 hours after the dose. TBW measurements in 8 of these subjects
      showed no significant differences, regardless of whether 2% or 10% water was
      used. We conclude that accurate estimates of TBW and body composition can be
      obtained with low-cost, 2% 18O-enriched water.

PMID- 8529765
TI  - [Blood glucose self-monitoring in diabetes. Recommendations of ALFEDIAM (French
      Language Association for the Study of Diabetes and Metabolic Diseases)].

PMID- 8529766
TI  - [Use of insulin in non-insulin-dependent diabetes (diabetes type 2).
      Recommendations of ALFEDIAM (French Language Association for the Study of
      Diabetes and Metabolic Diseases)].

PMID- 8529767
TI  - [Microalbuminuria and non-insulin-dependent diabetes: practical interpretation
      and therapeutic consequences].

PMID- 8529768
TI  - Risk factors and their identification. Third Part: Examples.
AB  - This is the final of a series of three articles in Diabete & Metabolisme which
      reviews the identification of risk factors of a disease, here: diabetes or
      complications of diabetes. In the first of the series [1], we gave the definition
      of a risk factor, along with measures of its force-relative risk and odds ratio,
      followed by the epidemiological definitions of the diseases: diabetes, coronary
      heart disease and hypertension. Risk factors were further discussed and we
      completed the discussion by some observations on the bias which can arise from a
      study or from its analysis, which can lead the researcher to the wrong
      conclusion. The three types of epidemiological studies which are used to
      determine whether factors are associated with a disease: observational or cross
      sectional studies, cohort studies and case-cohort studies are described in the
      second of the series [2]. Examples were provided of each of these study types and
      their advantages and disadvantages were discussed. This final paper provides some
      examples of the study types and the identification of risk factors from the
      literature. The first examples involve diabetes and pancreatic cancer, the second
      birth weight and non-insulin dependent diabetes. Having found an association
      between a risk factor and a disease, we then discuss whether it can be considered
      to be a risk factor, and if so and whether it is likely to be a cause of the
      disease.

PMID- 8529769
TI  - The impact of bone loss in women with endometriosis.
AB  - Low peak adult bone mass in a premenopausal woman puts her at increased risk for
      osteoporosis postmenopausally. Episodes of hypo-estrogenism premenopausally are
      associated with loss of bone density. This is seen with gonadotropin-releasing
      hormone agonist therapy for endometriosis, and thus prolonged or repeated courses
      of such treatment may increase the future risk of osteoporosis. Danazol and
      related compounds do not result in any bone loss but may have certain metabolic
      disadvantages.

PMID- 8529770
TI  - Changes in bone mineral content following hormone treatment for endometriosis.
AB  - The effects of danazol and buserelin on the bone mineral content (BMC) of 19
      Japanese women with endometriosis were studied. Subjects received 24-week courses
      of oral danazol (400 mg/day) or intranasal buserelin (900 micrograms/day).
      Trabecular BMC of the 3rd lumbar vertebra (L3) was monitored by computerized
      tomography scans pretreatment, at the end of treatment and 6 months post
      treatment. In the buserelin group there was a significant decrease in BMC (10
      25.4%, P < 0.01) which was not fully reversed 6 months after therapy, and
      increased parameters of bone resorption. In the danazol group, there was a slight
      gain in BMC despite a decrease in serum estrogen. Danazol and buserelin have
      similar success in the treatment of endometriosis, but the decrease in BMC at L3
      suggests that cumulative bone loss may follow repeated buserelin therapy.

PMID- 8529771
TI  - Danazol and plasma lipoprotein metabolism.
AB  - The potential long-term impact of danazol on coronary risk hinges on its effect
      on lipoprotein metabolism rather than its influence on total plasma lipids.
      Danazol may exert a regulatory influence on three key processes in lipoprotein
      metabolism: hepatic lipase activity; low-density lipoprotein receptor function;
      and lecithin:cholesterol acyl-transferase activity. Danazol decreases plasma
      fibrinogen and lipoprotein (a) levels, promotes fibrinolysis and causes a rise in
      plasminogen. Such changes are beneficial as they inhibit the process of
      thrombosis. Androgenic properties of danazol produce effects of plasma lipids and
      lipoproteins which oppose estrogen-induced changes. The usual recipients of
      danazol therapy are premenopausal females, in whom the absolute risk of ischemic
      heart disease is low. If the drug were shown to increase ischemic heart disease
      risk, detrimental factors must be weighted against its considerable and proven
      clinical benefits.

PMID- 8529772
TI  - Pain recurrence: a quality of life issue in endometriosis.
AB  - Studies reveal endometriosis to be present in 38-51% of women undergoing
      laparoscopy for chronic pelvic pain. Symptoms attributable to endometriosis
      include dysmenorrhea, dyspareunia, generalized pelvic pain, dyschezia, and
      radiation of pain to the back or leg. Psychological factors may also contribute
      to a more intense pain experience. Medical therapy provides symptom relief in 72
      93% of patients, although recurrence is common following treatment
      discontinuation. Surgical therapy has had varying results for long-term pain
      relief; adequacy of the initial surgical treatment appears to be a critical
      factor. Important adjunctive measures include presacral neurectomy and excisional
      techniques to remove deep, fibrotic, retroperitoneal lesions. The quality of life
      of women with endometriosis will improve with greater focus on achieving the long
      term relief of pelvic pain. Limitation of pain recurrence would benefit the
      patient greatly, by providing symptom relief and preventing the cycle of its
      probably adverse effects on physical activity, work productivity, sexual
      fulfilment, and mood.

PMID- 8529773
TI  - Immunological aspects of endometriosis.
AB  - During the past decade, evidence has accumulated indicating an association
      between endometriosis and changes in humoral and cell-mediated immunity. However,
      it is not clear whether immune changes are the sequelae or play a role in the
      etiopathogenesis of the disease. The latter concept is supported by the
      observation that exposure of rhesus monkeys to radiation or immunotoxicants leads
      several years later to an increase in frequency and severity of endometriosis.
      Studies from our laboratories support the theory that endometrial cells misplaced
      during menses can implant in ectopic locations only in women with genetically or
      environmentally altered cell-mediated immune function. Development of
      endometriosis may then prompt a humoral response in some women, which results in
      the production of autoantibodies to endometrial cells or cell-derived antigens.
      These autoantibodies may cross-react with the uterine endometrium, interfere with
      implantation, and cause infertility or early spontaneous abortions. We recently
      observed that the presence of autoantibodies in endometriosis was associated with
      significantly lower in vitro fertilization/embryo transfer pregnancy rates.
      Interestingly, in about 30% of women with unexplained infertility, immune changes
      characteristic of endometriosis were also present, suggesting a subclinical form
      of this disease. We conclude that: (1) women with unexplained infertility should
      have studies of the immune function to rule out subclinical form of
      endometriosis; (2) evaluation of infertility in women with endometriosis should
      include an assessment of autoantibody status; and (3) treatment methods involving
      autoantibody suppression should be considered in women with endometriosis
      positive for autoantibodies.

PMID- 8529774
TI  - Lower respiratory tract infection therapy--the role of ciprofloxacin.
AB  - Lower respiratory tract infections account for a large proportion of prescribed
      antibiotics and, with emerging resistance to standard agents, the introduction of
      the fluoroquinolones, in particular ciprofloxacin, has provided a further
      component in the armamentarium. This review encompasses 37 published clinical
      trials which featured ciprofloxacin; 3274 patients with lower respiratory tract
      infections were treated with this agent; in 94.1% of patients treatment was
      clinically successful and 90.9% of cases showed eradication of the causative
      pathogen. When these data were supplemented with previously unpublished
      information from the clinical trial database, specific organism eradication rates
      of 86.1%, 96.2% and 94.6% for Streptococcus pneumoniae, Haemophilus influenzae
      and Moraxella catarrhalis, respectively, were observed. These findings suggest
      that the high respiratory tissue penetration of ciprofloxacin and the achievable
      minimum inhibitory concentrations lead to acceptable clinical outcomes in lower
      respiratory tract infections.

PMID- 8529775
TI  - Sensitivity of Staphylococcus aureus, isolated from skin infections in 1994, to
      19 antimicrobial agents.
AB  - The most common pathogen causing skin infections is Staphylococcus aureus and the
      incidence of multiply resistant strains of S. aureus has been increasing. The in
      vitro susceptibility of 130 isolates of S. aureus to 19 antimicrobial agents:
      ampicillin (ABPC), methicillin, cefaclor, cefpodoxime proxetil, gentamicin,
      erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, norfloxacin,
      ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin,
      nadifloxacin and grepafloxacin, was evaluated by agar dilution tests. The S.
      aureus isolates were isolated from 130 patients with skin infections in 1994. The
      proportion of methicillin-resistant S. aureus isolates among the strains isolated
      was 19.2%. The concentration needed to inhibit 50% of the isolates was 3.13 mg/ml
      or less for all of the drugs, but the concentration needed to inhibit 90% of
      isolates was over 12.5 micrograms/ml, except in the cases of minocycline,
      vancomycin, fusidic acid, tosufloxacin and nadifloxacin. Tosufloxacin and
      nadifloxacin had the lowest minimum inhibitory concentrations. None of the S.
      aureus strains was resistant to nadifloxacin.

PMID- 8529776
TI  - Loperamide oxide for the treatment of chronic diarrhoea in Crohn's disease.
AB  - Loperamide oxide was compared with placebo for the treatment of chronic diarrhoea
      in patients with Crohn's disease. After initially receiving 2 mg loperamide oxide
      or placebo, hospital out-patients with Crohn's disease were instructed to take
      one tablet of loperamide oxide (1 mg) or placebo after passage of each unformed
      stool in a 1-week double-blind investigation. Patients who responded to this
      treatment by passing less than three unformed stools per 24 h continued to
      receive the drug, twice daily, for a further week. At the end of the initial 1
      week treatment phase both the investigator's and the patients' global evaluations
      of efficacy were significantly in favour of the active treatment (P = 0.025 and P
      = 0.020, respectively). The investigator's assessment of the change in abdominal
      pain was significant for loperamide oxide (P = 0.020) but not for placebo.
      Improvements in patient-rated severity of diarrhoea were significantly greater
      for loperamide oxide than for placebo (P = 0.046). The mean daily dose of
      loperamide oxide was 2.7 mg. During the second week, both the investigator's and
      the patients' assessments of global efficacy and symptom improvement continued to
      favour loperamide oxide though the differences were not significant. Adverse
      events were rare. The results suggest that loperamide oxide (3 mg/per day)
      provides a safe and effective treatment for the chronic diarrhoea associated with
      Crohn's disease.

PMID- 8529777
TI  - Effects on health of dietary supplementation with 100 mg d-alpha-tocopheryl
      acetate, daily for 6 years.
AB  - To evaluate the clinical antioxidant effects of vitamin E, 161 healthy volunteers
      aged 39 to 56 years, were given 100 or 3 mg of d-alpha-tocopheryl acetate orally
      daily for 6 years using a randomized, double-blind design. Among the 147
      volunteers who qualified for the analysis, seven of the 73 volunteers receiving 3
      mg d-alpha-tocopheryl acetate daily and none of the 74 volunteers receiving 100
      mg had coronary disorders including myocardial damage (P < 0.02). ST or T wave
      abnormalities on electrocardiograms were considered to indicate coronary
      disorders (four volunteers). The mean serum total tocopherol (TOC) concentration
      in the 100-mg group was significantly higher than that in the 3-mg group 6 months
      after the start of the study, and this raised value was maintained throughout the
      study; the level in the 3-mg group did not change significantly from the baseline
      value. The low-density lipoprotein cholesterol/total TOC ratio, a parameter of
      the inhibition of peroxidation of low-density lipoprotein cholesterol, was the
      only serum lipid parameter that was significantly different, at baseline, in the
      volunteers with coronary disorders compared with the others. These findings
      indicate that long-term supplementation with 100 mg tocopheryl acetate daily may
      prevent the early stages of coronary atherosclerosis by decreasing peroxidation
      of low-density lipoprotein cholesterol.

PMID- 8529778
TI  - Comparative incidence of allergy in the presence or absence of cancer.
AB  - Depression of the immune system may be related to cancer development. Allergic
      manifestations are due to enhanced immunological activity. Several authors have
      found lower rates of malignancy in atopic individuals. To elucidate the
      relationship between cancer and allergy, the prevalence of allergic
      manifestations was surveyed in 400 healthy controls and 400 patients with cancer.
      The number of allergies was significantly higher (P < 0.001) in the control group
      than in patients with cancer. Women were more atopic than men in both groups (P <
      0.001) but skin colour did not affect the prevalence of allergies. The type of
      cancer was not related to any specific allergic manifestation. The results
      suggest that allergies occur less frequently in men than in women and less
      frequently in patients with cancer than in healthy controls but these
      relationships are complex and depend on other factors that need further
      investigation.

PMID- 8529779
TI  - Cardiosympathetic neuropathy is independent of cardioparasympathetic neuropathy
      in patients with non-insulin-dependent diabetes mellitus.
AB  - The relationship between cardiosympathetic neuropathy and cardioparasympathetic
      neuropathy was investigated in 103 patients with non-insulin-dependent diabetes
      mellitus. Cardioparasympathetic nerve function was assessed by comparing
      electrocardiographically the expiratory and inspiratory R-R interval ratios,
      during a period of deep breathing, and the coefficients of variation of the R-R
      intervals. Cardiosympathetic nerve function was assessed by determining the
      uptake of [123I]metaiodobenzyl guanidine into the myocardium. The results
      indicate that there is no significant correlation between cardioparasympathetic
      and cardiosympathetic nerve function.

PMID- 8529780
TI  - Open randomized study comparing doxycycline and co-amoxiclav in the treatment of
      acute suppurative tracheobronchitis in adults. The Collaborative Group of the
      Centre Universitaire de Medecine Generale de L'Universite Libre de Bruxelles
      (CUMG-ULB) Investigators.
AB  - Doxycycline and co-amoxiclav were compared in a randomized clinical trial
      involving adult patients with acute suppurative tracheobronchitis. Patients were
      treated for 5 to 10 days with either antibiotic following three schemes: co
      amoxiclav 500 mg three times daily, or doxycycline 200 mg on day 1 followed by
      100 mg daily, or 200 mg daily. Assessment after 5-9 days was based only on
      clinical parameters. Patients with inadequate response to the initial treatment
      were crossed over to the alternative antibiotic. Of the 210 patients enrolled,
      206 were available for evaluation of efficacy. Both antibiotic regimens proved
      equally efficacious, with rates of clinical response (cure or improvement) of 89%
      and 91% for doxycycline and coamoxiclav, respectively. Patients who were crossed
      over to the alternative antibiotic had a significantly lower cure rate after
      their second course of antibiotics (22% compared with 70%). Adverse effects, most
      often of gastro-intestinal origin, were more common in the co-amoxiclav group
      than in the doxycycline-treated group, but rarely caused cessation of treatment.

PMID- 8529781
TI  - How blood pressure in patients with non-insulin-dependent diabetes mellitus is
      influenced by stress.
AB  - The effects of reducing stress on blood pressure were investigated in 20 patients
      with non-insulin-dependent diabetes mellitus. An anxiolytic, fludiazepam, was
      administered to the patients for 12 weeks and their blood pressures and State
      Trait Anxiety Inventory scores at the beginning and end of treatment were
      compared. Systolic and diastolic blood pressures and trait and state anxiety
      scores were all significantly reduced during the treatment period. There was also
      a weak correlation between the extent of the improvement in the same anxiety
      score and the improvement in diastolic blood pressures.

PMID- 8529782
TI  - Age at diagnosis of non-insulin-dependent diabetes mellitus in southern Iran.
AB  - To obtain an estimate of the age at onset of non-insulin-dependent diabetes
      mellitus in southern Iran, the medical records of the confirmed diabetic patients
      who attended the diabetes and endocrine clinics in southern Iran from March 1984
      to February 1993 were reviewed. The case records of 2566 patients, in whom non
      insulin-dependent diabetes mellitus was considered most probable, and who were
      resident in southern Iran at the time of diagnosis, were studied; they included
      1176 (45.8%) men and 1390 (54.2%) women. The age at diagnosis of the disease in
      men ranged between 18 and 82 years with a mean of 45.6 +/- 11.4 (+/- SD) years,
      and in women, between 15 and 83 with a mean of 44.3 +/- 12.2 (+/- SD) years.
      There was no statistically significant sex-related difference in the mean age at
      diagnosis of non-insulin-dependent diabetes mellitus in these patients. Sex
      specific rates showed a female to male ratio of 1.25 to 1. Age-specific rates
      indicated that non-insulin-dependent diabetes mellitus was most often diagnosed
      before age 55 and most commonly in the forties.

PMID- 8529783
TI  - The treatment of non-gonococcal urethritis with single dose oral azithromycin.
AB  - In an uncontrolled study, the efficacy of azithromycin in the treatment of non
      gonococcal urethritis was assessed in 41 male patients aged between 20 and 40
      years with a mean age of 27 +/- 5 years. Clinical and microbiological diagnosis
      confirmed that 28 men were found positive for Chlamydia trachomatis, 10 for
      Ureaplasma urealyticum and three for both C. trachomatis and U. urealyticum. All
      patients received 1 g azithromycin orally (four 250 mg capsules). The length of
      time between the treatment and following visits were 7-10 days and 14-21 days for
      second and third visits, respectively. Complete eradication was achieved in 27
      out of 41 patients. Of the remaining 14, six were found positive for C.
      trachomatis and were excluded as they did not return for the follow-up visit, one
      patient did not achieve complete eradication, one patient infected with both C.
      trachomatis and U. urealyticum failed to achieve complete eradication, and six
      patients infected with U. urealyticum failed to be completely cured. No adverse
      effects were reported in any patient. Single dose administration of 1 g
      azithromycin appears to be an effective and well-tolerated treatment for
      chlamydial urethritis and an advantage in terms of patient compliance.

PMID- 8529784
TI  - Plasma cortisol and vocalization responses of postweaning age guinea pigs to
      maternal and sibling separation: evidence for filial attachment after weaning.
AB  - Postweaning guinea pigs housed with their mother and littermates since birth
      vocalized more and exhibited greater increases in plasma cortisol levels when
      placed for 1 hr into a novel test cage alone than they did when tested in the
      identical fashion with the mother present. These responses were apparent beyond
      50 days of age, but had waned by 90 days of age. When tested with a familiar
      sibling cagemate, postweaning guinea pigs emitted fewer vocalizations than when
      tested alone but exhibited no less of an elevation of plasma cortisol levels.
      These results were obtained regardless of whether the subjects had been housed
      with mother and littermates from birth until the time of testing or with mother
      and littermates until weaning and then just the single sibling cagemate until the
      time of testing. The present findings closely approximate those seen in
      preweaning guinea pigs during tests of maternal and sibling separation, and
      indicate that guinea pigs can continue to exhibit a specific attachment to the
      mother beyond the time of weaning.

PMID- 8529785
TI  - On the importance of evolution to developmental psychobiology.
AB  - The term developmental psychobiology implies an integration between psychology
      and biology. But what segment of biology does the discipline embrace? The present
      commentary asserts that developmental psychobiology devotes too much attention to
      structural biology, with its emphasis on proximate mechanisms, and fails to give
      enough prominence to evolutionary biology and ultimate perspectives. I have
      attempted to portray the significance of evolution to developmental psychobiology
      and to elaborate on how developmental psychobiology might contribute to
      refinements in evolutionary theory, especially recent modifications that advocate
      a greater role for developmental processes. Methodological suggestions are
      offered, which would broaden developmental psychobiology's perspective so that a
      more comprehensive analysis of behavioral development results.

PMID- 8529786
TI  - Effects of opioid receptor blockade on the social behavior of rhesus monkeys
      living in large family groups.
AB  - Rhesus monkeys of 9 weeks, 48 weeks, 100 weeks, 150 weeks of age (young
      subjects), or mature parous females that were not lactating were given acute
      single doses of the opioid antagonist naloxone (0.5 mg/kg) and vehicle on
      different days and observed in their familial social groups. Naloxone increased
      the occurrence of affiliative behaviours. Young subjects spent more time in
      contact with their mothers but showed no changes in social grooming. Maternal
      contact was actively sought through contact vocalizations, decreasing proximity,
      and, for the youngest infants, increased attempts to suckle. Mature females made
      more solicitations for grooming and received more grooming from their companions.
      These results are interpreted in terms of naloxone blocking the positive effect
      arising from social contact and thus causing subjects to seek further affiliative
      comfort.

PMID- 8529787
TI  - Methodological issues in coding sleep states in immature infants.
AB  - Thirty-five healthy, premature infants, ranging from 30-39 weeks postconceptional
      age, were observed continuously for 6 to 24 hr. Behavioral state and
      electroencephalographic patterns were coded for each minute. Using these data,
      three questions regarding coding of states of sleep were addressed: What is the
      concordance between behavioral codes and specific EEG patterns? Does the
      concordance between behavioral codes and EEG patterns change with
      postconceptional age? What range of error can be expected when observation
      periods shorter than 24-hr are used to estimate the daily distribution of quiet
      sleep (QS) and active sleep (AS)? With behavioral codes as the standard,
      concordances of EEG patterns for QS and AS were 72.5 and 92.1% respectively. With
      EEG patterns as the standard, behavioral codes for QS and AS agreed 83.0 and
      88.9%. Agreement between behavioral codes and EEG patterns for QS increased with
      age. Finally, variation in estimates of the daily distribution of QS and AS
      decreased dramatically as the length of observation increased from 3 to 24 hr.

PMID- 8529788
TI  - Significance of Autocrine and Paracrine Signaling for Energy Metabolism in
      Contracting Skeletal and Cardiac Muscle Tissues. Symposium proceedings.
      Buhlerhohe, Germany, September 3-4, 1994.

PMID- 8529789
TI  - The coupling of glucose metabolism and perfusion in human skeletal muscle. The
      potential role of endothelium-derived nitric oxide.
AB  - Insulin-mediated glucose metabolism in skeletal muscle is associated with a
      commensurate increase in muscle perfusion. The link between insulin action and
      vasodilation may be mediated by endothelium-derived nitric oxide (EDNO). The
      evidence suggests that insulin causes an increase in the production of EDNO in
      insulin-sensitive but not insulin-resistant subjects. This defect in insulin
      mediated vasodilation may contribute to 1) enhanced pressor sensitivity and 2)
      reduced rates of insulin-mediated glucose uptake. We propose that the endothelium
      is an insulin target tissue that exhibits an increase in the release of EDNO in
      response to insulin. We postulate that the insulin-resistant state of obesity is
      associated with insulin resistance at the level of the endothelium, reduced EDNO
      release, and impaired vasodilation. Thus EDNO may act as the mediator coupling
      glucose metabolism to vasodilation. The interaction between insulin and the
      endothelium to enhance EDNO release describes a novel insulin action that
      deserves further exploration.

PMID- 8529790
TI  - Potential role of bradykinin in forearm muscle metabolism in humans.
AB  - Using the euglycemic-hyperinsulinemic glucose clamp and the human forearm
      technique, we have demonstrated that the improved glucose disposal rate observed
      after the administration of an angiotensin-converting enzyme (ACE) inhibitor such
      as captopril may be primarily due to increased muscle glucose uptake (MGU). These
      results are not surprising because ACE, which is identical to the bradykinin (BK)
      degrading kininase II, is abundantly present in muscle tissue, and its inhibition
      has been observed to elicit the observed metabolic actions via elevated tissue
      concentrations of BK and through a BK B2 receptor site in muscle and/or
      endothelial tissue. These findings are supported by several previous studies.
      Exogenous BK applied into the brachial artery of the human forearm not only
      augmented muscle blood flow (MBF) but also enhanced the rate of MGU. In another
      investigation, during rhythmic voluntary contraction, both MBF and MGU increased
      in response to the higher energy expenditure, and the release of BK rose in the
      blood vessel, draining the working muscle tissue. Inhibition of the activity of
      the BK-generating protease in muscle tissue (kallikrein) with aprotinin
      significantly diminished these functional responses during contraction. Applying
      the same kallikrein inhibitor during the infusion of insulin into the brachial
      artery significantly reduced the effect of insulin on glucose uptake into forearm
      muscle. This is of interest, because in recent studies insulin has been suggested
      to elicit its actions on MBF and MGU via the accelerated release of endothelium
      derived nitric oxide, the generation of which is also stimulated by BK in a
      concentration-dependent manner. This new evidence obtained from in vitro and in
      vivo studies sheds new light on the discussion of whether BK may play a role in
      energy metabolism of skeletal muscle tissue.

PMID- 8529791
TI  - Modulation of insulin receptor signaling. Potential mechanisms of a cross talk
      between bradykinin and the insulin receptor.
AB  - Insulin resistance of the skeletal muscle plays a key role in the development of
      the metabolic endocrine syndrome and its further progression to type II diabetes.
      Impaired signaling from the insulin receptor to the glucose transport system and
      to glycogen synthase is thought to be the cause of skeletal muscle insulin
      resistance. An incomplete activation of the insulin receptor tyrosine kinase,
      which is found in type II diabetes, appears to contribute to the pathogenesis of
      the signaling defect. Available data suggest that the impaired tyrosine kinase
      function of the insulin receptor is not due to an inherited defect but rather is
      caused by a modulation of insulin receptor function. We used rat-1 fibroblasts
      and NIH-3T3 cells stably overexpressing human insulin receptor and 293 cells
      transiently overexpressing human insulin receptor to characterize conditions
      modulating the signaling function of the insulin receptor kinase. Using these
      cell models, we could demonstrate that activation of different protein kinase C
      (PKC) isoforms by high glucose levels or phorbol esters causes a rapid inhibition
      of the receptor tyrosine kinase activity. This effect is most likely mediated
      through serine phosphorylation of the receptor beta-subunit. It can be prevented
      by PKC inhibitors and the new oral antidiabetic agent thiazolidindione. The data
      suggest that PKC might be an important negative regulator of insulin receptor
      function. Because we have recently shown that bradykinin activates different
      isoforms of PKC in these cell types, an inhibitory cross talk between the
      bradykinin receptor and the insulin receptor through PKC activation seemed
      possible. However, we were unable to observe an insulin receptor tyrosine kinase
      inhibition through bradykinin, suggesting that different isoforms of PKC are
      activated by hyperglycemia and bradykinin. On the other hand, a modulation of
      bradykinin signals by insulin could be demonstrated in these cells. Bradykinin
      induced tyrosine phosphorylation of proteins of approximately 130 and 70 kDa was
      inhibited by insulin treatment of rat-1 fibroblasts. These data suggest that
      signals from the insulin receptor modify signaling from the bradykinin receptor
      to tyrosine phosphorylation of different cellular proteins.

PMID- 8529792
TI  - Effects of treatment of spontaneously hypertensive rats with the angiotensin
      converting enzyme inhibitor trandolapril and the calcium antagonist verapamil on
      the sensitivity of glucose metabolism to insulin in rat soleus muscle in vitro.
AB  - We measured the sensitivity of glucose metabolism to insulin in soleus muscle
      preparations isolated from spontaneously hypertensive (SH) rats and normotensive
      age-matched Wistar-Kyoto (WKY) rats. SH rats were treated with the angiotensin
      converting enzyme (ACE) inhibitor trandolapril (1 mg/kg) and/or a second
      antihypertensive drug, the calcium antagonist verapamil, alone (100 mg/kg) or as
      combination therapy (50 mg/kg). Treatment of SH rats with trandolapril or
      trandolapril in combination with verapamil for 6 weeks normalized the blood
      pressure. The estimated concentration of insulin required for half-maximal
      stimulation of glycogen synthesis (i.e., EC50 values) was approximately 500
      microU/ml for muscles from both WKY and SH rats. This value is five times higher
      than the value obtained from soleus muscle preparations isolated from insulin
      sensitive Wistar rats. This indicates that glycogen synthesis is insensitive to
      insulin in SH and WKY rat soleus muscle. Treatment of SH rats with trandolapril
      with or without verapamil improved the sensitivity of glycogen synthesis to
      insulin in soleus muscle. Further experiments investigated whether acute exposure
      (1 h) of insulin-sensitive skeletal muscle with either trandolaprilat (the active
      metabolite of trandolapril) or bradykinin (levels of which may be raised by ACE
      inhibition) could affect the insulin-stimulated rate of glucose metabolism. These
      results show that both trandolaprilat and bradykinin caused a small but
      significant increase in the rates of glucose metabolism. In conclusion, 1) SH and
      WKY rat skeletal muscle was insulin resistant, 2) chronic treatment of SH rats
      with trandolapril with or without verapamil normalized blood pressure and
      improved the response of glycogen metabolism to insulin, and 3) bradykinin and
      trandolaprilat acutely caused a small but significant increase in the rate of
      glycogen synthesis to a submaximal physiological concentration of insulin.

PMID- 8529793
TI  - Glucose transport activity in insulin-resistant rat muscle. Effects of
      angiotensin-converting enzyme inhibitors and bradykinin antagonism.
AB  - Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis
      of NIDDM and is associated with hypertension, obesity, and dyslipidemia.
      Angiotensin-converting enzyme (ACE) inhibitors are used primarily in
      antihypertensive therapy but also are known to improve whole-body insulin
      mediated glucose disposal. However, the exact site of action is not well
      characterized. We have used the isolated epitrochlearis muscle from a well
      established animal model of skeletal muscle insulin resistance, the obese Zucker
      rat, to test the effect of oral administration of ACE inhibitors on insulin
      sensitive muscle glucose transport activity. Both acute and chronic
      administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non
      sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in
      vitro insulin-mediated muscle glucose transport activity. In addition, the acute
      effect of oral captopril administration was completely abolished by pretreatment
      of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings
      indicate that ACE inhibitors may improve whole-body glucose metabolism by acting
      on the insulin-sensitive skeletal muscle glucose transport system. In addition,
      bradykinin or one of its metabolites may be involved in the action of the ACE
      inhibitor captopril on insulin-resistant muscle.

PMID- 8529794
TI  - Kallikreins and kinins. Molecular characteristics and cellular and tissue
      responses.
AB  - Kallikrein-kininogen-kinin systems are now topics of widespread interest. The
      long-standing appreciation of their diverse pharmacological properties and
      biochemical characteristics is being supplemented by modern definitions of their
      cellular receptors' signal-transduction mechanisms and physiological and
      pathological roles. The assignment of important homeostatic responsibilities for
      kinins, including those in autocrine and paracrine signaling for skeletal and
      cardiac muscle energy metabolism, is now subject to definitive experimental
      evaluation via the availability of better kallikrein inhibitors, specific kinin
      receptor antagonists, and techniques of genetic manipulation.

PMID- 8529795
TI  - Skeletal muscle kallikrein. Potential role in metabolic regulation.
AB  - Skeletal muscle glucose metabolism appears to be regulated by locally derived
      factors as well as by systemically circulating hormones. Local factors may be
      particularly important during exercise, when substrate demand can increase
      rapidly. Numerous studies in perfused limbs suggest that the kallikrein-kinin
      system may participate in the regulation of substrate delivery and utilization by
      skeletal muscle. Evidence also suggests that kinins mediate the increase in
      insulin sensitivity after administration of converting enzyme inhibitors. Tissue
      kallikrein has been isolated and purified from rat skeletal muscles, and its
      level is highest in muscle with high oxidative activity. In other tissues,
      kallikrein synthesis is under the influence of insulin. It has not been possible
      to demonstrate effects of kallikrein or kinins on glucose metabolism in isolated
      skeletal muscle or cardiocytes. Therefore modulation of glucose metabolism by
      kallikrein or kinins may only be observed in intact perfused tissues or organs.

PMID- 8529796
TI  - Immunolocalization of bradykinin B2 receptors on skeletal muscle cells.
AB  - The kallikrein-kinin system has been implicated in the inflammatory process,
      blood pressure regulation, renal homeostasis, and glucose utilization. The
      effects of kallikrein and kinin on glucose uptake by the skeletal muscle are well
      established; however, the occurrence and the cellular distribution of the kinin
      receptor(s) mediating these effects in the striated muscle are unknown. Using
      anti-peptide antibodies raised against the predicted intra- and extracellular
      domains of the B2 receptor and the peroxidase/antiperoxidase system, we have been
      able to detect the B2 receptor on the plasma membrane of striated skeletal muscle
      cells of the rat hindlimb. A strong immunostaining appeared as a rim of
      immunoreactive material located on the periphery of striated muscle cells. Cross
      sectioned and longitudinally sectioned cells revealed a similar staining pattern.
      Alternatively, the immunostaining with specific antibodies to tissue kallikrein
      and to T-kininogen did not yield a significant staining of the striated muscle
      cells. Localization of the B2 receptor on the surface of striated muscle cells
      provides a structural basis for the hypothesized physiological functions of the
      kinin system in the skeletal muscle.

PMID- 8529797
TI  - Bradykinin B2 receptors on skeletal muscle are coupled to inositol 1,4,5
      trisphosphate formation.
AB  - To determine the presence of bradykinin receptors in skeletal muscle, we examined
      in both displacement and saturation studies the binding of [125I-Tyr8]bradykinin
      or [3H]bradykinin in three types of skeletal muscle preparations: membrane
      fractions from guinea pig hindlimb quadriceps, dog semimembranosus and
      semitendinosus muscles, and L8 rat skeletal muscle myoblasts. Scatchard analysis
      of [125I-Tyr8]bradykinin x bradykinin competition binding demonstrated specific
      bradykinin binding of 4.9 and 3.2 fmol/mg protein in dog and guinea pig skeletal
      muscle preparations, respectively. Unlabeled bradykinin specifically displaced
      [125I-Tyr8]bradykinin with IC50 values of 36.5 +/- 6 and 118.0 +/- 16.0 pmol/l
      from dog and guinea pig muscle membranes, respectively. The B2 bradykinin
      receptor antagonist HOE 140 and the B1 bradykinin receptor antagonist des
      Arg9[Leu8]bradykinin displaced the binding of [3H]bradykinin from dog membranes
      with IC50 values of 0.38 and 217.3 nmol/l, respectively, suggesting that
      bradykinin binds to a B2-type receptor. In addition, unlabeled bradykinin
      competed with [3H]bradykinin for binding to dog skeletal muscle membrane
      preparations in a biphasic manner. To assess whether this represents multiple
      bradykinin receptor subtypes present in skeletal muscle homogenates or several
      affinity states of a single binding site, we examined bradykinin receptors on a
      pure skeletal muscle system, the L8 neonatal rat skeletal muscle myoblast cell
      line. These myoblasts also contain specific [3H]bradykinin-binding sites with a
      Bmax of 271 fmol/mg protein and a Kd of 0.83 nmol/l. Competitive agonist binding
      curves were biphasic (high-affinity IC50 = 3.9 pmol/l, low-affinity IC50 = 22.6
      nmol/l) in the absence of guanosine 5'-O-(3-thio-trisphosphate) (GTP gamma S);
      they shifted to a model of one affinity (8.1 nmol/l) in the presence of GTP gamma
      S. Because the enzyme neutral endopeptidase 24.11 is an important kininase in
      skeletal muscle, we examined the effect of the neutral endopeptidase inhibitor
      phosphoramidon on the binding of bradykinin to dog skeletal muscle membranes. We
      found that phosphoramidon decreased the apparent Bmax from 7.3 to 5.8 fmol/mg
      protein. In addition, in this cell line we investigated the action of bradykinin
      on phosphoinositide hydrolysis. Inositol 1,4,5-trisphosphate (IP3) was measured
      with a radioreceptor assay. Bradykinin (0.1 nmol/l to 1 mumol/l) induced IP3
      formation in a dose-dependent manner (EC50 = 1.42 nmol/l) from a basal level of
      72.8 +/- 16 pmol/mg protein to 433 +/- 35.5 at the highest (1 mumol/l)
      concentration. We conclude that bradykinin B2 receptors are expressed in skeletal
      muscle. Phosphoinositide hydrolysis upon stimulation of this receptor is an
      indicator of intracellular signal transduction. Part of the bradykinin binding in
      skeletal muscle is due to interaction with the enzyme neutral endopeptidase.

PMID- 8529798
TI  - Kininase II-type enzymes. Their putative role in muscle energy metabolism.
AB  - Because of the importance of bradykinin in improving heart function in some
      conditions or in enhancing glucose uptake by skeletal muscle, we investigated
      kininases in these tissues. In P3 fraction of the heart and skeletal muscles,
      angiotensin I-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) are
      the major kininases, as determined first with specific substrates and second with
      bradykinin. ACE activity was highest in guinea pig heart (2.7 +/- 0.07 mumol.h
      1.mg protein-1) but decreased in other species in this order: dog atrium, rat
      heart, dog ventricle, and human atrium. The specific activity of NEP was lower:
      0.45 mumol.h-1.mg protein-1 in cultured neonatal cardiac myocytes and varying
      between 0.12 and 0.05 mumol.h-1.mg protein-1 in human, dog, rat, and guinea pig
      heart. In the skeletal muscle P3, ACE was most active in guinea pig and rat (1.2
      and 1.1 mumol.h-1.mg protein-1, respectively) but less so in dog (0.09 mumol.h
      1.mg protein-1). NEP activity was higher in dog P3 (0.28 mumol.h-1.mg protein-1)
      but lower in rat and guinea pig (0.19 and 0.1 mumol.h-1.mg protein-1,
      respectively). Continuous density gradient centrifugation enriched NEP activity
      in dog and rat (from 0.3 to 1.0 and 0.49 mumol.h-1.mg protein-1, respectively).
      Immunoprecipitation with antiserum to purified NEP proved the specificity of the
      rat enzyme. Bradykinin (0.1 mmol/l) was inactivated in the presence and absence
      of inhibitors by rat skeletal muscle NEP, as measured by high-performance liquid
      chromatography. Here, 36% of the activity was caused by NEP and 19% by ACE. In
      radioimmunoassay (bradykinin 10 nmol/l), 46 and 55% of kininase in rat and dog
      skeletal muscle P3, respectively, was due to ACE; 36 and 28%, respectively, was
      due to NEP. Aside from these enzymes, an aminopeptidase in rat P3 also
      inactivates bradykinin. Thus, in conclusion, heart and skeletal muscle membranes
      contain kininase II-type enzymes, but their activity depends on the species.

PMID- 8529799
TI  - Hypotheses regarding the role of pericytes in regulating movement of fluid,
      nutrients, and hormones across the microcirculatory endothelial barrier.
AB  - A decade ago, we initiated studies to define relationship(s) between products of
      5-lipoxygenase-mediated arachidonic acid metabolism and altered microvascular
      permeability. Patients with permeability (nonhydrostatic) pulmonary edema (adult
      respiratory distress syndrome) and intact animal models of permeability edema,
      produced with agents that required neutrophils (phorbol myristate acetate) and
      those that did not (ethchlorvynol), invariably revealed the presence of
      leukotrienes; in contrast, leukotrienes were not detected in cases of hydrostatic
      pulmonary edema. In isolated perfused canine lung, we identified increases in
      microvascular permeability coefficients in response to the injurious agent.
      Permeability coefficients were not increased when injurious agents were given in
      the presence of 5-lipoxygenase inhibitors. To define further the relationships
      between leukotriene generation and edema formation, we postulated that
      leukotrienes effected contraction of capillary pericytes, thereby increasing pore
      size of endothelial intercellular junctions and enhancing movement across the
      microvascular barrier. We isolated pericytes from bovine retinas, identified them
      morphologically and by staining characteristics, and, in preliminary experiments,
      found that they do not possess the 5-lipoxygenase enzyme; however, when
      cocultured with neutrophils, which possess 5-lipoxygenase but cannot synthesize
      sulfidopeptide leukotrienes because of their lack of glutathione S-transferase,
      sulfidopeptide leukotriene synthesis ensued. In view of the anatomic position of
      pericytes, evidence that they participate in endothelial transport, their ability
      to contract, and evidence of cell-to-cell communication, we propose that
      pericytes control the movement of fluid, solutes, hormones, and small and large
      molecules across the microvascular endothelium.

PMID- 8529801
TI  - Role of kinins in the pathophysiology of myocardial ischemia. In vitro and in
      vivo studies.
AB  - In ischemia, the heart generates and releases kinins as mediators that seem to
      have cardioprotective actions. Kinin-generating pathways are present in the
      heart. Kininogen, kininogenases, kinins, and B2 kinin receptors can be measured
      in cardiac tissue. Kinins are released under conditions of ischemia. In
      anesthetized rats and dogs with coronary artery ligation and in human patients
      with myocardial infarction, kinin plasma levels are increased. In isolated rat
      hearts, the outflow of kinins is enhanced during ischemia but markedly attenuated
      after deendothelialization, pointing to the coronary vascular endothelium as the
      main possible source. Kinins administered locally exert beneficial cardiac
      effects. In isolated rat hearts with ischemia-reperfusion injuries, perfusion
      with bradykinin (BK) reduces the duration and incidence of ventricular
      fibrillation, improves cardiodynamics, reduces release of cytosolic enzymes, and
      preserves energy-rich phosphates and glycogen stores. In anesthetized animals,
      intracoronary BK is followed by comparable beneficial changes and limits infarct
      size. Inhibition of breakdown of BK and related peptides induces beneficial
      cardiac effects. Treatment with ACE inhibitors such as ramipril increases cardiac
      kinin levels and reduces post-ischemic reperfusion injuries in isolated rat
      hearts and infarct size in anesthetized animals. The importance of an intact
      endothelium that continuously generates kinins is supported by observations that
      basal and ramipril-induced release of kinins and PGI2 is markedly reduced after
      deendothelialization of isolated hearts. Blockade of B2 kinin receptors increases
      ischemia-induced effects. Endothelial formation of NO and PGI2 by ACE inhibition
      is prevented by the specific B2 kinin receptor antagonist icatibant. In isolated
      hearts, ischemia-reperfusion injuries deteriorate with icatibant, which also
      abolishes the cardioprotective effects of ACE inhibitors and of exogenous BK.
      Infarct size reduction by ACE inhibitors and by BK in anesthetized animals is
      reversed by icatibant. Kinins contribute to the cardioprotective effects
      associated with ischemic preconditioning because preconditioning or BK-induced
      antiarrhythmic and infarct size-limiting effects are attenuated by icatibant. In
      conclusion, kinins may act as mediators of endogenous cardioprotective
      mechanisms. Kinins are generated and released during ischemia, with subsequent
      formation of PGI2 and NO probably derived mainly from the coronary vascular
      endothelium. Their cardioprotective profile resembles that of ACE inhibitors.

PMID- 8529800
TI  - B2 bradykinin receptors in cultured neonatal rat cardiomyocytes mediate a
      negative chronotropic and negative inotropic response.
AB  - Receptors for bradykinin (BK) were characterized in primary cultures of beating
      neonatal rat cardiomyocytes using [3H]BK was radioligand. Degradation studies
      demonstrated that [3H]BK was stable for at least 2 h when incubated with
      cardiomyocytes at 2 and 37 degrees C in the presence of bacitracin in combination
      with captopril or ramiprilat. Without these inhibitors, > 80% of the [3H]BK was
      degraded within 2 h at 37 degrees C. This indicates that angiotensin-converting
      enzyme (ACE) is responsible for the main BK-degrading activity in cardiomyocytes.
      Scatchard plots were linear and gave a Kd of 1.5 +/- 0.8 nmol/l (mean +/- SD, n =
      4) and a maximum binding capacity of 55-125 fmol/mg protein. Association and
      dissociation studies showed that binding of [3H]BK was saturable and reversible.
      Binding of [3H]BK at 37 degrees C led to internalization of the ligand.
      Competition studies with B1 and B2 agonists and antagonists were consistent with
      a B2 subtype of receptor. Addition of BK to beating cardiomyocytes (> 1 nmol/l)
      at 37 degrees C gave a strong but transient negative chronotropic effect. This
      response was paralleled by changes in the pulsation amplitude, which indicated a
      simultaneous negative inotropic effect of BK. These results provide a basis for
      the hypothesis that ACE inhibition exerts its cardioprotective effect at the
      level of a population of cardiomyocytes by virtue of kinin receptor-mediated
      mechanisms.

PMID- 8529802
TI  - Substrate metabolism, hormone interaction, and angiotensin-converting enzyme
      inhibitors in left ventricular hypertrophy.
AB  - Left ventricular hypertrophy is considered to be an independent risk factor
      giving rise to ischemia, arrhythmias, and left ventricular dysfunction. Slow
      movement of intracellular calcium contributes to the impaired contraction and
      relaxation function of hypertrophied myocardium. Myofibril content may also be
      shifted to fetal-type isoforms with decreased contraction and relaxation
      properties in left ventricular hypertrophy. Myocyte hypertrophy and interstitial
      fibrosis are regulated independently by mechanical and neurohumoral mechanisms.
      In severely hypertrophied myocardium, capillary density is reduced, the diffusion
      distance for oxygen, nutrients, and metabolites is increased, and the ratio of
      energy-production sites to energy-consumption sites is decreased. The metabolic
      state of severely hypertrophied myocardium is anaerobic, as indicated by the
      shift of lactate dehydrogenase marker enzymes. Therefore, the hypertrophied
      myocardium is more vulnerable to ischemic events. As a compensatory response to
      severe cardiac hypertrophy and congestive heart failure, the ADP/ATP carrier is
      activated and atrial natriuretic peptide is released to increase high-energy
      phosphate production and reduce cardiac energy consumption by vasodilation and
      sodium and fluid elimination. However, in severely hypertrophied and failing
      myocardium, vasoconstrictor and sodium- and fluid-retaining factors, such as the
      renin-angiotensin system, aldosterone, and sympathetic nerve activity, play an
      overwhelming role. Angiotensin-converting enzyme inhibitors (ACEIs) are able to
      prevent cardiac hypertrophy and improve cardiac function and metabolism. Under
      experimental conditions, these beneficial effects can be ascribed mainly to
      bradykinin potentiation, although a contribution of the ACEI-induced angiotensin
      II reduction cannot be excluded.

PMID- 8529803
TI  - Insulin-induced glucose transporter (GLUT1 and GLUT4) translocation in cardiac
      muscle tissue is mimicked by bradykinin.
AB  - The effect of bradykinin on glucose transporter translocation in isolated rat
      heart was compared with the effect of insulin. Hearts from male obese (fa/fa)
      Zucker rats were perfused under normoxic conditions and constant pressure in a
      classic Langendorff preparation with 12 mmol/l glucose as substrate, and a set of
      functional parameters was measured simultaneously. Bradykinin was administered at
      a concentration (10(-11) mmol/l) that did not increase coronary flow. Insulin was
      used at a concentration (8 x 10(-8) mmol/l) known to maximally stimulate glucose
      transport in this model. After 15 min of perfusion with insulin or bradykinin,
      subcellular membrane fractions of the heart were prepared, and distribution of
      glucose transporter protein (GLUT1 and GLUT4) in fractions enriched with surface
      membranes (transverse tubules [TTs] and sarcolemmal membranes [PMs]) and with low
      density microsomal membranes (LDMs) were determined by immunoblotting with the
      respective antibodies. Both glucose transporter isoforms were translocated after
      stimulation with insulin (increased transporter protein content in the PM+TT
      enriched fraction with a concomitant decrease in the LDM-enriched fraction) and,
      to a smaller extent, also with bradykinin. These data suggest that in hearts of
      insulin-resistant obese (fa/fa) Zucker rats, bradykinin interacts with or
      facilitates the translocation process of both GLUT1 and GLUT4.

PMID- 8529804
TI  - Insulin-induced redistribution of GLUT4 glucose carriers in the muscle fiber. In
      search of GLUT4 trafficking pathways.
AB  - Insulin rapidly stimulates glucose transport in muscle fiber. This process
      controls the utilization of glucose in skeletal muscle, and it is deficient in
      various insulin-resistant states, such as non-insulin-dependent diabetes
      mellitus. The effect of insulin on muscle glucose transport is mainly due to the
      recruitment of GLUT4 glucose carriers to the cell surface of the muscle fiber.
      There is increasing evidence that the recruitment of GLUT4 carriers triggered by
      insulin affects selective domains of sarcolemma and transverse tubules. In
      contrast, GLUT1 is located mainly in sarcolemma and is absent in transverse
      tubules, and insulin does not alter its cellular distribution in muscle fiber.
      The differential distribution of GLUT1 and GLUT4 in the cell surface raises new
      questions regarding the precise endocytic and exocytic pathways that are
      functional in the muscle fiber. The current view of insulin-induced GLUT4
      translocation is based mainly on studies performed in adipocytes. These studies
      have proposed the existence of intracellular compartments of GLUT4 that respond
      to insulin in a highly homogeneous manner. However, studies performed in skeletal
      muscle have identified insulin-sensitive as well as insulin-insensitive
      intracellular GLUT4-containing membranes. These data open a new perspective on
      the dynamics of intracellular GLUT4 compartments in insulin-sensitive cells.

PMID- 8529805
TI  - Molecular responses of endothelial tissue to kinins.
AB  - The endothelial response to kinin stimulation is the result of a series of
      complex intracellular reactions involving changes in the intracellular
      concentration of free calcium ([Ca2+]i) and intracellular pH, enhanced
      phosphorylation of several proteins via the activation of at least four distinct
      families of protein kinases, and activation of membrane ion transport systems.
      Some of the more recent developments in this field suggest that endothelial
      tyrosine kinases and tyrosine phosphatases as well as serine/threonine
      phosphatases are also activated in response to bradykinin. In addition, the
      finding that the mitogen-activated protein kinase (MAP kinase) pathway was
      tyrosine phosphorylated, and presumably activated, in endothelial cells after an
      increase in [Ca2+]i has wideranging implications for these cells. Indeed, MAP
      kinase recognizes many different substrates in the cell, including growth factor
      receptors, microtubule-associated proteins, specific serine-threonine protein
      kinases, phospholipase A2, and transcription factors. Further recent studies of
      interest have underscored the role of endothelium-derived hyperpolarizing factor
      in addition to nitric oxide and prostacyclin in the coronary vasculature. Indeed,
      this mediator, which seems to be an endothelium-derived, cytochrome P450-derived
      metabolite of arachidonic acid, would now appear to represent a substantial
      constitutive component of the vasodilator response to bradykinin.

PMID- 8529806
TI  - Inhibition of angiotensin type 1 receptor prevents decline of glucose transporter
      (GLUT4) in diabetic rat heart.
AB  - There is some evidence that inhibition of angiotensin-converting enzyme (ACE)
      activity can improve the uptake and conversion of glucose by heart and skeletal
      muscle in diabetes. To study the underlying mechanisms, we treated streptozotocin
      induced diabetic rats with the angiotensin type 1 receptor (AT1) antagonist ICI
      D8731 and the ACE inhibitor fosinopril for 4 months and determined the expression
      of the myocardial glucose transporter proteins. In diabetic rats, the expression
      of the insulin-regulated glucose transporter (GLUT4) was strongly diminished as
      shown by Western and Northern blots. ICI D8731 prevented the decrease of GLUT4
      protein in diabetes but had no influence on the amount of mRNA encoding for GLUT1
      and GLUT4. GLUT1 protein was hardly detected in the rat heart and was affected
      neither by diabetes nor by treatment with the AT1 antagonist. Additionally, ICI
      D8731 influenced the translocation of GLUT4 from the intracellular pool to the
      plasma membrane, because treatment increased the amount of GLUT4 protein in the
      plasma membranes as well as in intracellular membrane fractions compared with
      membranes of untreated diabetic control rats. In contrast, inhibition of ACE by
      fosinopril influenced neither the expression nor the translocation of the glucose
      transporter proteins. These observations indicate that angiotensin II has a
      distinct influence on the post-transcriptional regulation of the GLUT4
      transporter protein, presumably indirectly as a consequence of hemodynamic
      effects and structural alterations of the vessel wall.

PMID- 8529807
TI  - Control of energy metabolism during muscle contraction.
AB  - Skeletal muscle energetics can be studied noninvasively at rest, during exercise,
      and in recovery using phosphorus nuclear magnetic resonance (31P-NMR). In resting
      muscle, inorganic phosphate (P(i)) and total cellular phosphate concentration are
      regulated by Na(+)-dependent P(i) transport. Insulin was shown to stimulate P(i)
      uptake in G-8 muscle cells, in isolated rat soleus muscle, and in human muscle in
      vivo under conditions of hyperinsulinemic-euglycemic clamp. The relationship
      between plasma P(i) and intracellular muscle P(i) was examined in a group of
      patients with elevated plasma P(i) resulting from renal failure. The total
      creatine content of muscle cells is controlled by an active creatine uptake in
      which beta 2-receptor stimulation and the activity of the Na(+)-K(+)-ATPase play
      a significant role. Recovery after exercise is entirely oxidative; the rate of
      ATP synthesis is largely controlled by ADP, the concentration of which is
      determined by the creatine kinase equilibrium that includes the concentration of
      H+. At the onset of aerobic dynamic exercise, ATP is maintained largely by
      glycolysis, producing lactic acid, and by phosphocreatine breakdown. After
      vasodilation, ATP synthesis becomes predominantly oxidative. The above processes
      can be quantitatively evaluated by 31P-NMR.

PMID- 8529808
TI  - Nuclear magnetic resonance studies of muscle and applications to exercise and
      diabetes.
AB  - Natural-abundance 13C nuclear magnetic resonance (NMR) spectroscopy is a
      noninvasive technique that enables in vivo assessments of muscle and/or liver
      glycogen concentrations. When directly compared with the traditional needle
      biopsy technique, NMR was found to be more precise. Over the last several years,
      we have developed and used 13C-NMR to obtain information about human glycogen
      metabolism both under conditions of altered blood glucose and/or insulin and with
      exercise. Because NMR is noninvasive, we have been able to obtain more data
      points over a specified time course, thereby dramatically improving the time
      resolution. This improved time resolution has enabled us to document subtleties
      of the resynthesis of muscle glycogen after severe exercise that have not been
      observed previously. An added advantage of NMR is that we are able to obtain
      information simultaneously about other nuclei, such as 31P. With interleaved 13C-
      and 31P-NMR techniques, we have been able to follow simultaneous changes in
      muscle glucose-6-phosphate and muscle glycogen. In this article, we review some
      of the work that has been reported by our laboratory and discuss the relevance of
      our findings for the management of diabetes.

PMID- 8529809
TI  - Significance of insulin for glucose metabolism in skeletal muscle during
      contractions.
AB  - Glucose uptake rate in active skeletal muscles is markedly increased during
      exercise. This increase reflects a multifactorial process involving both local
      and systemic mechanisms that cooperate to stimulate glucose extraction and
      glucose delivery to the muscle cells. Increased glucose extraction is effected
      primarily via mechanisms exerted within the muscle cell related to the
      contractile activity per se. Yet contractions become a more potent stimulus of
      muscle glucose uptake as the plasma insulin level is increased. In addition,
      enhanced glucose delivery to muscle, which during exercise is essentially
      effected via increased blood flow, significantly contributes to stimulate glucose
      uptake. Again, however, increased glucose delivery appears to be a more potent
      stimulus of muscle glucose uptake as the circulating insulin level is increased.
      Furthermore, contractions and elevated flow prove to be additive stimuli of
      muscle glucose uptake at any plasma insulin level. In conclusion, the extent to
      which muscle glucose uptake is stimulated during exercise depends on various
      factors, including 1) the intensity of the contractile activity, 2) the magnitude
      of the exercise-associated increase in muscle blood flow, and 3) the circulating
      insulin level.

PMID- 8529810
TI  - Assessment of the developmental toxicity of ethylene glycol applied cutaneously
      to CD-1 mice.
AB  - Ethylene glycol (EG; CAS No. 107-21-1) is teratogenic to mice by whole-body
      exposure to an aerosol at high concentrations, but results were confounded by
      possible exposure from ingestion after grooming and/or from percutaneous
      absorption. Therefore, CD-1 mice were exposed to EG on Gestational Days (GD) 6
      through 15, 6 hr/day by occluded cutaneous application at 0, 12.5, 50, or 100%
      (undiluted) EG (0.1 ml/animal, equivalent to approximately 0, 404, 1677, or 3549
      mg/kg/day [10 ml/kg, positive control gavage (PCGG)], 30 females/group. Dams were
      weighed and evaluated daily (including application site) for clinical signs and
      water consumption throughout gestation. On GD 18, maternal uterus, liver, and
      paired kidneys were weighed; kidneys of 0 and 100% and the PCGG were examined
      microscopically. Corpora lutea and implantation sites were recorded. Live fetuses
      were weighed, sexed, and examined for structural alterations. For cutaneously
      exposed dams, there was no treatment-related maternal, no differences in pre- or
      postimplantation loss in fetal body weights/litter, and no increased incidences
      of any fetal malformations. Two skeletal variations, increased at 100% may
      represent effects of restraint stress and/or findings due to chance. In the PCGG,
      8 females (26.7%) died, water consumption was increased, fetal body
      weights/litter were reduced, and fetal malformations and variations were
      increased. PCGG kidneys exhibited tubular nephrosis and tubular cell
      degeneration, with no oxalate crystals, documenting renal toxicity at this oral
      dose in mice. Minimal-grade renal tubular lesions observed in 3 mice (of 30) at
      100% EG may represent treatment-related or incidental findings. Therefore,
      exposure of pregnant CD-1 to 0, 12.5, 50 or 100% EG during organogenesis by
      occluded cutaneous application resulted in minimal or no observable maternal or
      developmental toxicity at 100% (approximately 3549 mg/kg/day), the NOEL.

PMID- 8529811
TI  - Acute cardiotoxicity of the Anti-HIV dideoxynucleoside, F-ddA, in the rat.
AB  - 2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA), an acid-stable, purine
      dideoxynucleoside with in vitro anti-HIV activity, has been selected by the NCI
      as a clinical trial candidate. A recent report that high, single doses of F-ddA
      produce cardiotoxicity in rats prompted the present investigation whose objective
      was to quantitate this effect and establish a relationship between this toxicity
      and F-ddA plasma concentrations. Microscopic examination of cardiac tissues for
      degenerative lesions established the effects of F-ddA and ddA on three iv
      schedules [daily x 1(2.5-250 mg/kg); daily x 5(125, 250 mg/kg), and BID x 1 (250
      mg/kg)] as well as one oral schedule [BID x 1 (500 mg/kg) using 8- to 12-week old
      female Sprague-Dawley rats. For both F-ddA and ddA, the group mean severity of
      the cardiac lesions was dose-dependent and proportional to the measured plasma
      concentrations of the undeaminated parent drugs. F-ddI and ddI, were essentially
      nontoxic in this study (iv, 250 mg/kg, daily x 1 and daily x 5), since plasma
      concentrations exceeding 2 mM produced only minimal cardiac lesions. The
      cardiomyopathy of F-ddA was minimal to mild for all iv doses except 250 mg/kg
      (daily x 1) and usually was greater than that of ddA at any given dose. This is a
      consequence of the fact that F-ddA is deaminated 20 times more slowly than ddA,
      resulting in higher plasma concentrations of F-ddA relative to ddA at any given
      time for any given dose. Neither F-ddA nor ddA was more cardiotoxic on a repeated
      iv schedule (daily x 5) than when administered only once, suggesting that rat
      cardiotoxicity is related Cmax rather than total exposure. In this most sensitive
      species, the formation of cardiac lesions above the background level is
      associated with i.v. F-ddA administration when the F-ddA plasma concentration
      approaches 300 microM, 30-50 times the anticipated therapeutic level in humans.

PMID- 8529813
TI  - Subchronic toxicity study in rats with 1-methyl-3-propylimidazole-2-thione (PTI):
      effects on the thyroid.
AB  - A 90-day gavage study was performed to evaluate the subchronic toxicity of 1
      methyl-3-propylimidazole-2-thione (PTI) when administered to Crl:CD BR rats. PTI
      is a chemical catalyst and is structurally similar to the thioureas, which are
      known to adversely affect the thyroid. Therefore, this study was designed to
      investigate the effects of PTI on the thyroid. Male and female rats were dosed
      with 0, 5, 10, 25, or 75 mgPTI/kg/day for 13 weeks. Clinical pathology
      examinations and pathology examination were performed and the following were
      measured periodically: serum T3, T4, and TSH, hepatic UDP-glucuronyltransferase
      activity, and cell proliferation of the thyroid and liver. Under the conditions
      of this study, the overall no-observed-adverse-effect level (NOAEL) for the
      subchronic effects of PTI in male and female rats was 10 mg PTI/kg/day. The NOAEL
      was based on the effects on the thyroid gland in male and female rats dosed with
      25 and 75 mg PTI/kg/day, as well as the hepatic centrilobular fatty change,
      increased severity of chronic progressive nephropathy, fatty change in the
      adrenal medulla, and the substantial reduction in body weight and body weight
      gain. The primary target organs were the thyroid and liver. Alterations in
      thyroid hormones (T3, T4, and TSH) occurred predominantly at 25 and 75 mg/kg/day.
      Toxicologically significant alterations in T3, T4, and TSH levels, cell
      proliferation, and UDP-glucuronyltransferase activity occurred in rats dosed with
      25 and 75 mg/kg/day, which correlated with organ weight and histopathological
      effects. Additionally, the effect of PTI on thyroid peroxidase activity, a key
      step in thyroid hormone synthesis, was evaluated in vitro using microswine
      thyroid microsomes. PTI was shown to inhibit thyroid peroxidase, with an IC50 of
      0.02 M. These data suggest that PTI enhances the excretion of T4 via induction of
      glucuronyltransferase and inhibits thyroid hormone synthesis via a direct affect
      on thyroid peroxidase. Both of these effects contribute to the disruption of the
      hypothalamic-pituitary-thyroid axis and result in sustained elevation of TSH and
      the corresponding thyroid hypertrophy and hyperplasia.

PMID- 8529812
TI  - Local versus systemic immunotoxicity of isobutyl nitrite following subchronic
      inhalation exposure of female B6C3F1 mice.
AB  - Female B6C3F1 mice were exposed to isobutyl nitrite (IBN) by inhalation at 0,
      37.5, 75, or 150 ppm for 6 hr per day, 5 days per week for 15 weeks. The
      potential of this compound to induce immunotoxicity was assessed during the 3rd,
      13th, 14th, and 15th week of exposure and after 2 weeks of recovery following the
      15 weeks of exposure. Both systemic and lung immune functions were examined,
      including body and lymphoid organs weights, pulmonary macrophage function and
      host defense, expression of splenic lymphocyte cell-surface markers, natural
      killer cell function, mixed lymphocyte reaction, and induction of specific
      antibody to a T-cell-dependent antigen. There was a dose-related suppression of T
      cell-dependent antibody-forming cell responses in the spleen following IBN
      exposure; however, other measures of T-cell and nonspecific immunity were not
      significantly affected. A dose-related increase of H202 production by alveolar
      macrophages was present after 12 but not after 68 exposures to IBN. In contrast,
      pulmonary host defense mechanisms against Klebsiella pneumoniae were unaffected.
      These results suggest that in the absence of changes in host resistance, IBN may
      have selective and partially reversible effects on the immune system.

PMID- 8529814
TI  - Diesel exhaust particulates induce nasal mucosal hyperresponsiveness to inhaled
      histamine aerosol.
AB  - The prevalence of allergic rhinitis is increasing in many countries. It has been
      reported that the prevalence rate of allergic rhinitis caused by pollens in air
      polluted areas are higher than than in nonpolluted areas. Therefore, it is
      important to determine whether air pollutants are related to the increase in the
      prevalence rate of allergic rhinitis. In this respect, it is necessary to
      elucidate whether exposure to air pollutants affects the nasal mucosa and causes
      nasal mucosal hyperresponsiveness to chemical mediators released by antigen
      antibody reactions. In the present study using guinea pigs, we investigated
      effects of diesel exhaust particulates on (1) nasal airway resistance, (2)
      increases in nasal airway resistance and secretion induced by histamine aerosol,
      and (3) vascular permeability and the increase in vascular permeability is an
      important factor involved in increased nasal airway resistance and secretion.
      Intranasal pressure and nasal secretion from the nostril were measured as markers
      of nasal airway resistance and exocrine activity of the nasal mucosa,
      respectively. A 30-min administration of a suspension of diesel exhaust
      particulates into the nasal cavities caused a significant increase in intranasal
      pressure. The administration also augmented an increase in intranasal pressure
      and nasal secretion induced by histamine aerosol. In dorsal skin, diesel exhaust
      particulates increased vascular permeability. Diesel exhaust particulates also
      augmented vascular permeability are potent by histamine. These properties of
      diesel exhaust particulates are likely derived in part from the augmentation
      vascular permeability by these particulates.

PMID- 8529815
TI  - Nonadditive developmental toxicity in mixtures of trichloroethylene, Di(2
      ethylhexyl) phthalate, and heptachlor in a 5 x 5 x 5 design.
AB  - In order to identify nonadditive effects on development, three compounds were
      combined using five dosages of each agent (a 5 x 5 x 5 full-bacterial design).
      Trichloroethylene (TCE), di(2-ethylhexyl) phthalate (DEHP), and heptachlor
      (HEPT), in corn oil, were administered by gavage to Fischer-344 rats on Gestation
      Days 6-15. Dose levels were 0, 10.1, 32, 101, and 320 mg/kg/day for TCE; 0, 24.7,
      78, 247, and 780 mg/kg/day for DEHP; and 0, 0.25, 0.8, 2.5, and 8 mg/kg/day for
      HEPT. The dams were allowed to deliver and their pups were weighed and examined
      postnatally. Maternal death showed no main effects but DEHP and HEPT were
      synergistic. For maternal weight gain on Gestational Days 6-8, main effects for
      all three agents were observed, as well as 6-8 main effects for all three agents
      were observed, as well as TCE-DEHP synergism, and DEHP-HEPT antagonism. Maternal
      weight gain on Gestational Days 6-20 adjusted for litter weight showed main
      effects for TCE and HEPT, but no interactions. Main effects for all three agents
      were evident for full-litter resorptions and prenatal loss. The HEPT main effects
      were unexpected and were interpreted as reflecting potentiation by HEPT of the
      other agents. For full-litter loss, the TCE-HEPT and DEHP-HEPT interactions were
      antagonistic, perhaps due to a "ceiling" effect. For prenatal loss, the TCE-DEHP
      interaction was synergistic. Postnatal loss showed DEHP and HEPT main effects but
      no interaction. Analysis of pup weights on Day 1 revealed TCE and DEHP main
      effects and DEHP-HEPT antagonism; on Day 6, DEHP and HEPT main effects, DEHP-HEPT
      antagonism, and TCE-DEHP synergism were evident. Microphthalmia and anophthalmia
      incidences revealed TCE and DEHP main effects but no interactions. This extensive
      examination of a full-factorial design elucidates the complexities of studying
      and interpreting mixture toxicity. The data are available for further analysis.

PMID- 8529816
TI  - Comparison of styrene hepatotoxicity in B6C3F1 and Swiss mice.
AB  - Inhalation exposure to styrene at concentrations that cause metabolic saturation
      results in significantly greater hepatotoxicity in B6C3F1 mice than in Swiss
      mice; females of both strains are more susceptible than males. These studies were
      conducted to investigate the mouse strain and gender differences in
      susceptibility to hepatotoxicity caused by repeated exposure to styrene at
      concentrations that do not cause metabolic saturation. Male and female B6C3F1 and
      Swiss mice (8 weeks old) were exposed to 0, 150, or 200 ppm styrene for 6 hr/day,
      5 days/week, for up to 2 weeks. Changes in body and liver weights, serum alanine
      aminotransferase (ALT) and sorbitol dehydrogenase (SDH) levels, liver
      histopathology, and total liver glutathione (GSH) were evaluated after 2, 3, 5,
      and 10 exposures (six mice/sex/strain/time point/concentration). Blood levels of
      styrene and styrene-7,8-oxide (SO) were measured in mice exposed to 200 ppm
      styrene for 2,3, or 5 days (six mice/sex/strain/time point/concentration). Serum
      ALT and SDH levels were significantly elevated only in female B6C3F1 mice after 3
      exposures to 200 ppm styrene; enzyme levels had returned to control levels when
      measured after 5 and 10 exposures. Degeneration and coagulative necrosis of
      centrilobular hepatocytes were observed in female B6C3F1 mice exposed 2, 3, and 5
      days to 150 or 200 ppm styrene; incidences of these lesions were greater in the
      200 ppm than in the 150 ppm dose group. After 10 days of exposure to 150 or 200
      ppm styrene, hepatocellular lesions had resolved, although a residual chronic
      inflammation was present in livers of most female B6C3F1 mice.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8529817
TI  - Triprolidine: 104-week feeding study in rats.
AB  - The antihistamine triprolidine hydrochloride, was fed at dietary concentrations
      of 0, 250, 1000, or 2000 ppm (as the free base) to groups of 60 Fischer 344
      (F344) rats of each sex for up to 2 years to evaluate its potential
      carcinogenicity. Up to 12 per sex from each group were killed at 65 weeks, and
      hematology, clinical chemistry, and histopathology were evaluated. A complete
      histopathological evaluation was performed on all other animals; survivors were
      killed at 2 years. Survival was significantly extended in triprolidine-treated
      males and females, particularly at the high dose. At the close of the study high
      dose males and females had gained significantly less body weight than controls.
      Among rats killed at 65 weeks females in the mid- and high-dose groups weighed
      significantly less than controls, but weights of control and dosed males were not
      significantly different. The incidences of numerous lesions tended to decrease
      with increasing triprolidine dose. In females, clitoral gland adenomas, thyroid c
      cell hyperplasia and neoplasia, mammary gland hyperplasia and fibroadenomas, and
      uterine stromal polyps, and in males, anterior pituitary gland adenomas,
      preputial gland neoplasia, thyroid c-cell pancreatic islet neoplasia, mononuclear
      cell leukemia, and the combination of lymphocytic, histiocytic, and
      undifferentiated cell malignant lymphomas and mononuclear leukemia, all exhibited
      negative dose trends. Cytoplasmic alterations of the parotid gland and numerous
      liver lesions tended to be more frequent in treated than in control animals.
      Liver lesions that exhibited positive dose trends include chronic inflammation
      and centrilobular fatty change in both sexes, mixed cell foci, and the
      combination of mixed cell foci and eosinophilic foci in females, and in males,
      basophilic foci and eosinophilic foci. Triprolidine was not carcinogenic in F344
      rats.

PMID- 8529818
TI  - Empirical modeling of particle deposition in the alveolar region of the lungs: a
      basis for interspecies extrapolation.
AB  - Different species exposed to the same particle atmosphere may not receive
      identical initial doses in comparable respiratory tract regions, and the
      selection of a certain species for toxicologic evaluation of inhaled particles
      may, thus, influence the estimated human lung, or systemic, dose, as well as its
      relationship to potential adverse health effects. Estimating regional particle
      deposition patterns is important for establishing the comparability of animal
      models, for understanding interspecies differences in the expression of chemical
      toxicities, and, ultimately, for the human risk assessment process. A method is
      described which offers a strategy for summarizing published data on regional
      deposition of particles of different diameters and calculating a deposited
      fraction for a particular particle size distribution. This involved the
      construction of nomograms to allow estimation of alveolar deposition fractions in
      three species, namely the human, monkey, and rat. A regression model was then
      developed to permit the calculation of more exact deposition fractions. Although
      this paper describes the procedure for one region of the lungs, the same
      technique can be applied to other regions of the respiratory tract or to the
      total system for which deposition data are available. While this technique may
      facilitate the interpretation of available experimental results and their
      application to human health risk assessment, appropriate caution should be
      exercised in applying the developed nomograms given limitations of the deposition
      database upon which it is based.

PMID- 8529819
TI  - Developmental toxicity of N-methylformamide administered by gavage to CD rats and
      New Zealand white rabbits.
AB  - N-Methylformamide (NMF) is a metabolite of dimethylformamide (DMF), a solvent
      with wide applications in the chemical industry. The potential developmental
      toxicity of NMF was evaluated in CD rats and New Zealand white rabbits. Pregnant
      rats and rabbits were dosed once daily by gavage on Gestation Days 6-15 and 6-18,
      respectively. Doses for rats were 0, 1, 5, 10, or 75 mg/kg; doses for rabbits
      were 0, 5, 10, or 50 mg/kg. Cesarean sections were performed on rats and rabbits
      on Gestation Days 20 and 29, respectively. No treatment-related maternal deaths
      or clinical signs occurred in either species. Body weight gain and food
      consumption were depressed in rats given 75 mg/kg and rabbits given 50 mg/kg.
      Fetal viability was reduced at 75 mg/kg in rats and at 50 mg/kg in rabbits. In
      rats, a significant increase in the incidence of malformations including
      cephalocele and sternoschisis was observed in fetuses from the 75 mg/kg group. In
      addition, a developmental delay was indicated by reduction of fetal weight and by
      a significant increase in the occurrence of incomplete ossification of various
      skeletal structures. In the rabbit, fetal body weight was reduced at 50 mg/kg.
      Malformations observed at 50 mg/kg included gastroschisis, cephalocele, domed
      head, flexed paw, and skull and sternum anomalies. The lowest-observed-adverse
      effect levels for maternal and developmental toxicity in the rat and rabbit were
      75 and 50 mg/kg, respectively. The no-observed-adverse-effect level for maternal
      and developmental toxicity in the rat and rabbit was 10 mg/kg.

PMID- 8529820
TI  - Developmental toxicity of amesergide administered by gavage to CD rats and New
      Zealand white rabbits.
AB  - Amesergide is a selective serotonin 5-HTIC/2 receptor antagonist being developed
      for the treatment of depression. The potential developmental toxicity of
      amesergide was evaluated in CD rats and New Zealand white rabbits. Pregnant rats
      and rabbits were dosed once daily by gavage on Gestation Days 6-17 and 6-18,
      respectively. Doses for rats were 0, 3, 10, and 30 mg/kg; doses for rabbits and
      0, 0.2, 2, and 15 mg/kg. Cesarean sections were performed on rats and rabbits on
      Gestation Days 20 and 28, respectively. In rats, maternal effects expressed as
      depression of body weight gain and food consumption were observed at the 30 mg/kg
      dose level. Fetal viability and morphology were not affected at any dose level.
      Fetal weight was depressed at the 30 mg/kg dose level. The no-observed-effect
      level (NOEL) in the rat was 10 mg/kg. In rabbits, maternal effects expressed as a
      decrease in food consumption occurred at the 2 and 15 mg/kg dose levels; weight
      gain was depressed at 15 mg/kg. Fetal viability, weight, and morphology were not
      affected at any dose level. The NOELs for maternal and developmental effects in
      the rabbit were 0.2 and 15 mg/kg, respectively.

PMID- 8529821
TI  - Chronic nephropathy and renal carcinogenicity of o-benzyl-p-chlorophenol in
      F344/N rats and B6C3F1 mice.
AB  - o-Benzyl-p-chlorophenol, an aryl halide biocide, was evaluated in male and female
      F344/N rats and B6C3F1 mice in a series of subchronic and 2-year toxicity and
      carcinogenicity studies. Kidney was the primary target of toxicity in the 13-week
      gavage studies in rats and mice, with increased nephropathy noted as low as 240
      mg/kg in male rats. Considering the nephropathy to be doselimiting, the chronic
      (2-year) study was conducted at lower doses (male rats: 30, 60, or 120 mg/kg;
      female rats: 60, 120, or 240 mg/kg; male and female mice: 120, 240, or 480 mg/kg;
      in corn oil; n = 50/group). Survival and body weights of dosed rats were similar
      to controls in the 2-year study. Survival of high-dose male and female mice, and
      body weights of all dosed male and mid- and high-dose female mice, were lower
      than controls. The incidence and severity of nephropathy increased with dose and
      length of treatment in both rats and mice. There was an increased incidence of
      renal tubule adenomas or carcinomas in both the mid- and high-dose male mice.
      Despite similar evidence of nephropathy, however, there were no increased
      incidences of neoplasms in female mice or in male or female rats. This study
      suggests therefore that while nephrotoxicity may have been a necessary component,
      factors other than the marked nephrotoxicity of o-benzyl-p-chlorophenol were
      critical to the development of renal carcinogenesis induced in only male mice.

PMID- 8529822
TI  - Induction of thymic lymphoma in mice administered the dideoxynucleoside ddC.
AB  - Groups of 10 male and 20 female B6C3F1 mice received 0, 500, or 1000 mg/kg/day
      2'3'-dideoxycytidine (ddC) by gavage for 13 weeks. At the end of the 13-week
      exposure period all males and 10 females per group were necropsied while the
      remaining females were held for 1 month without further treatment. Thymic atrophy
      was present at the 13-week necropsy in male and female mice administered 1000
      mg/kg/day and in females administered 500 mg/kg/day, but was not present in
      females following 1 month of recovery. Thymic lymphoma was present in 1 female
      that received 500 mg/kg/day and 1 female that received 1000 mg/kg/day. In a
      follow-up study groups of 70 female mice received 0, 500, or 1000 mg/kg/day for
      13 weeks. At the end of the 13-week exposure period 20 mice per group were
      necropsied and the remaining animals held for 3 months without further treatment.
      Thymic atrophy was observed in ddC-exposed groups at the 13-week necropsy but not
      in mice allowed to recover for 13 weeks. Thymic lymphoma occurred in 3/50 mice
      that received 500 mg/kg/day and in 17/50 mice that received 1000 mg/kg/day but
      did not occur in mice from the vehicle control group.

PMID- 8529823
TI  - Cataractogenesis in rats induced by in utero exposure to RG 12915, a 5-HT3
      antagonist.
AB  - RG 12915, a selective 5-HT3 antagonist developed for the treatment of emesis and
      nausea associated with cancer chemotherapy, was administered by gavage to four
      groups of pregnant rats from Gestation Day 6 to 17 at doses of 0, 1, 10, and 100
      mg/kg/day, as part of a Segment II (developmental toxicity) study. The 100
      mg/kg/day dose was maternally toxic as indicated by decreased body weight gain
      and food consumption during the treatment period. A portion of the rats were
      allowed to deliver and rear their litters and three pups from two litters in the
      100 mg/kg/day group were observed to have lens opacities (visible to the naked
      eye) at weaning. At a later examination, when the offspring were approximately 4
      months old, four additional animals from the same two litters had cataracts. A
      slight growth retardation was also observed postweaning in the offspring of the
      100 mg/kg/day group. To confirm the lens findings and more precisely define the
      no-effect dose, another study was conducted in which pregnant rats were
      administered daily RG 12915 doses of 0, 10, 30, 60, or 100 mg/kg/day from
      Gestation Day 6 to 17. There was a dose-related decrement in maternal body weight
      gain during the treatment period in the 30, 60, and 100 mg/kg/day groups (12, 28,
      and 47%, respectively) compared to the control group. A treatment-related
      incidence of nuclear cataract was observed in the offspring of the 60 and 100
      mg/kg/day groups (litter incidence 6 and 45%, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8529824
TI  - Peroxisome proliferation and microsomal enzyme induction by the hypolipidemic CI
      924 in rats and mice: relationship to tumorgenicity.
AB  - CI-924 (5'5'-[1,1'-biphenyl]-2,5-diylbis(oxy)]bis [2,2-dimethyl-pentanoic acid]),
      a lipid lowering agent, was previously shown to be hepatotumorigenic in male and
      female B6C3F1 mice but not in male and female albino Wistar rats. To determine if
      the difference between the species in tumorigenic response correlated with the
      extent of peroxisome proliferation or microsomal changes the effects of CI-924 on
      liver were characterized in rats and mice. CI-924 doses of 0, 25, 75, and 150
      mg/kg were administered in the diet for 4 weeks to B6C3F1 mice and albino Wistar
      rats. Peroxisomal beta-oxidation activity was significantly increased in all
      groups at doses of 25 mg/kg or higher and was induced up to 25 times in male
      rats. Peroxisomal carnitine acyltransferase and acyl-CoA oxidase activities were
      also increased, with the greatest induction observed in male rats. Catalase
      activity quadrupled in rats and doubled in mice. Serum liver enzyme activities
      were unchanged with the exception of 5'nucleotidase which was elevated in mice
      and decreased in male, but not female, rats. Glutathione S-transferase decreased
      in the males of both species and glutathione peroxidase increased in the mice.
      Cytochrome P450 4A1 increased in both species at doses of 25 mg/kg or greater and
      correlated with increased lauric acid hydroxylation. The high degree of
      peroxisome proliferation in male rats was unexpected in light of the lack of
      tumorgenicity demonstrated in a previous 2-year study and these results indicate
      that early peroxisome proliferation alone is not always a good predictor of
      hepatocarcinogenicity.

PMID- 8529825
TI  - Effects of estrogen, progesterone, and methoxychlor on surgically induced
      endometriosis in rats.
AB  - Endometriosis is a disease of women where endometrial tissue is found growing at
      ectopic sites. While evidence suggesting a role for the ovarian hormones in
      endometriosis exists, no complete studies of the roles of estrogen and
      progesterone have heretofore been performed. Also, if estrogen has a role in the
      growth and/or maintenance of endometriosis, it is likely that the proestrogenic
      pesticide, methoxychlor (MXC), might also have such an effect. Sixty rats
      underwent surgery on Day 0 to induce endometriosis. On Day 21, all rats were
      ovariectomized. During surgery, the diameters of all endometriotic implants
      (which were fully developed) were measured. Starting on Day 21, groups of rats
      were treated daily, for 3 weeks, with (a) vehicle (b) estrone, 1 micrograms/rat,
      E;(c) progesterone, 2 mg/rat, P; (d) E + P, 1 micrograms + 2 mg; (e) MXC, 250
      mg/kg; or (f) MXC + P, 250 mg/kg + 2 mg/rat. On Day 42, all rats were killed, and
      the diameters of all endometriotic sites were measured. While no differences in
      diameter were found across groups prior to ovariectomy, ovariectomy plus
      treatment altered the growth of endometriosis tissue. Progesterone and vehicle
      treatments produced results that were identical: regression of endometriotic
      sites. Both estrogen and MXC treatments maintained endometriotic site size at a
      level greater than that in the vehicle-treated group. The combination of
      progesterone with either estrone or MXC did not alter the effect of either
      chemical. We conclude that while estrogen promotes the growth of endometriosis,
      progesterone either produces regression or fails to maintain the sites. MXC, at a
      relatively high dose, supports the development of endometriosis. Concurrent
      progesterone treatment does not modulate the effects of estrone or MXC. These
      results suggest that exposure of women to high doses of MXC may exacerbate the
      development of endometriosis or contribute to its recurrence.

PMID- 8529826
TI  - Uptake, disposition, and persistence of acrylonitrile in rainbow trout.
AB  - The uptake and disposition of [2,3-14C]acrylonitrile-derived 14C were studied in
      rainbow trout by water exposure. Trout were exposed to [14C]ACN at 5.3
      micrograms/liter and sampled at various times during a 24-hr uptake phase. After
      transfer to fresh water, fish were sampled to 72 hr for the estimation of
      elimination rates and the half-life of 14C. Throughout these experiments several
      fish were also sacrificed for whole-body autoradiography. The uptake of 14C in
      carcass and viscera began to level off at 24 hr and the apparent elimination
      studies, the 14C appeared to persist in both muscle and octanol-water partition
      coefficient (log p = -0.92). The t1/2 of 14C in muscle in two such experiments
      was calculated to be 117 and 102 hr. The autoradiographs of whole-body sections
      of exposed trout also revealed a slow loss of 14C from muscle. Muscle extracts
      prepared from exposed fish were essentially nondialyzable. When dialyzed muscle
      extract was analyzed for protein and 14C after SDS-PAGE electrophoresis, most of
      the 14C was associated with a single protein band with a mobility comparable to
      standards in the 10,000 Dalton range. These studies indicate that the long
      halflife of 14C seen in trout muscle may be due to covalent binding of 14C to a
      protein with a molecular weight of approximately 10,000 Daltons.

PMID- 8529827
TI  - Toward public understanding of science.

PMID- 8529828
TI  - A need to "reinvent" the Clinton administration's approach to science and
      technology.

PMID- 8529829
TI  - The Internet biologist.

PMID- 8529830
TI  - Flavoprotein structure and mechanism. 8. Structure-function relations for old
      yellow enzyme.
AB  - The past 5 years have seen tremendous progress in our knowledge of old yellow
      enzyme (OYE) as a number of OYEs have been cloned and expressed, a high
      resolution crystal structure has been determined for one of these, and new
      substrates have been found that can be turned over by the enzyme. Together these
      studies do not yet define the physiological role of OYE, but they lead to
      significant new insights into the enzymatic properties and structure-function
      relations of OYE.

PMID- 8529831
TI  - Liver regeneration. 2. Role of growth factors and cytokines in hepatic
      regeneration.
AB  - During liver regeneration quiescent hepatocytes undergo one or two rounds of
      replication and then return to a nonproliferative state. Growth factors regulate
      this process by providing both stimulatory and inhibitory signals for cell
      proliferation. EGF, TGF alpha, and HGF stimulate DNA synthesis in hepatocytes in
      vivo and in culture but the sensitivity of cultured hepatocytes to the mitogenic
      effects of these factors is much higher than that of quiescent hepatocytes in
      intact livers. We have proposed that after partial hepatectomy, hepatocytes enter
      a state of replicative competence ("priming") before they can fully respond to
      growth factors. The priming step is an initiating event in liver regeneration
      that involves the activation and DNA binding of NF-kappa B and other
      transcription factors, which could be induced by TNF or other cytokines. EGF, TGF
      alpha, and HGF have major effects on liver growth. TGF alpha expression
      correlates with hepatocyte DNA synthesis during liver development and growth and
      the constitutive expression of the factor confers proliferative activity to adult
      hepatocytes in vivo and in culture. The data indicate that the activity of
      stimulatory and inhibitory growth factors such as TGF beta 1 and activin is low
      in normal livers but that the expression of both types of factors increase during
      liver regeneration.

PMID- 8529832
TI  - Protein motifs. 8. The triple-helix motif in proteins.
AB  - The triple helix is an important motif found in the family of collagens as well
      as a set of host-defense proteins. This conformation may be identified by its
      strict sequence constraints, including glycine as every third residue and a high
      content of imino acids. The first high-resolution structure available for a
      triple helix has confirmed the model of three supercoiled polyproline II-like
      helices and has defined a highly ordered water network whose regularity depends
      on the presence of 4-hydroxyproline. The role of the rod-like triple helix lies
      in its capacity to self-associate in a variety of forms as well as its ability to
      bind a wide range of ligands. The extensive hydrogen-bonded water network,
      together with the high content of sterically restricted imino acids, are the
      major contributors to the stabilization of triple helices, whereas electrostatic
      and hydrophobic interactions define intermolecular association and ligand
      binding. Mutations in the repeating Gly-X-Y sequences of triple helices have been
      shown to cause a variety of human diseases.

PMID- 8529833
TI  - Introduction: the colorful, fascinating world of the carotenoids: important
      physiologic modulators.

PMID- 8529834
TI  - Structure and properties of carotenoids in relation to function.
AB  - The basic principles of structure, stereochemistry, and nomenclature of
      carotenoids are described and the relationships between structure and the
      chemical and physical properties on which all the varied biological functions and
      actions of carotenoids depend are discussed. The conjugated polyene chromophore
      determines not only the light absorption properties, and hence color, but also
      the photochemical properties of the molecule and consequent light-harvesting and
      photoprotective action. The polyene chain is also the feature mainly responsible
      for the chemical reactivity of carotenoids toward oxidizing agents and free
      radicals, and hence for any antioxidant role. In vivo, carotenoids are found in
      precise locations and orientations in subcellular structures, and their chemical
      and physical properties are strongly influenced by other molecules in their
      vicinity, especially proteins and membrane lipids. In turn, the carotenoids
      influence the properties of these subcellular structures. Structural features
      such as size, shape, and polarity are essential determinants of the ability of a
      carotenoid to fit correctly into its molecular environment to allow it to
      function. A role for carotenoids in modifying structure, properties, and
      stability of cell membranes, and thus affecting molecular processes associated
      with these membranes, may be an important aspect of their possible beneficial
      effects on human health.--Britton, G. Structure and properties of carotenoids in
      relation to function.

PMID- 8529835
TI  - The role of molecular chaperones in protein folding.
AB  - Folding of newly synthesized polypeptides in the crowded cellular environment
      requires the assistance of so-called molecular chaperone proteins. Chaperones of
      the Hsp70 class and their partner proteins interact with nascent polypeptide
      chains on ribosomes and prevent their premature (mis)folding at least until a
      domain capable of forming a stable structure is synthesized. For many proteins,
      completion of folding requires the subsequent interaction with one of the large
      oligomeric ring-shaped proteins of the chaperonin family, which is composed of
      the GroEL-like proteins in eubacteria, mitochondria, and chloroplasts, and the
      TRiC family in eukaryotic cytosol and archaea. These proteins bind partially
      folded polypeptide in their central cavity and promote folding by ATP-dependent
      cycles of release and rebinding. In these reactions, molecular chaperones
      interact predominantly with the hydrophobic surfaces exposed by nonnative
      polypeptides, thereby preventing incorrect folding and aggregation.

PMID- 8529836
TI  - Phosphorylation of paired helical filament tau in Alzheimer's disease
      neurofibrillary lesions: focusing on phosphatases.
AB  - The major brain abnormalities in patients with Alzheimer's disease (AD) include
      extracellular deposits of beta-amyloid, intraneuronal neurofibrillary lesions,
      and the massive loss of specific subsets of telencephalic neurons.
      Neurofibrillary lesions contain paired helical filaments (PHFs) that accumulate
      in the perikarya (e.g., neurofibrillary tangles) and processes (e.g., dystrophic
      neurites, neuropil threads) of selectively vulnerable telencephalic neurons. The
      subunits of PHFs are derivatized forms of central nervous system (CNS) tau
      proteins (CNS tau) known collectively as PHFtau. Until very recently it was
      thought that the aberrant phosphorylation of PHFtau was the most salient
      difference between normal human CNS tau and PHFtau. However, this view required
      modification when it was shown that fetal and biopsy-derived human CNS tau
      proteins were phosphorylated at nearly all of the same sites found in PHFtau,
      albeit to a lesser extent. More significantly, these and other studies may be
      interpreted to suggest that the abnormal phosphorylation of PHFtau may result
      from the failure of protein phosphatases (i.e., PP2A and 2B) to dephosphorylate
      PHFtau. In this review, we summarize current understanding of the role of kinases
      and phosphatases in pathogenesis of PHFtau. We then consider how the formation
      PHFtau in neurons could disrupt the microtubule network, impair axonal transport,
      and compromise the viability of neurons, thereby contributing to the onset and
      progression of AD.

PMID- 8529837
TI  - TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial
      cell gene expression and function.
AB  - Cytokines are a group of secreted proteins that display diverse biological
      activity. They are especially important in the body's response to injury. They
      subserve a variety of both autocrine and paracrine functions by activating
      numerous intracellular second-messenger signaling pathways. Cytokines are known
      to mediate many inflammatory processes, and the inappropriate presence of
      cytokines in the central nervous system (CNS) has been implicated in a number of
      disease states. This article focuses on the biological role of two cytokines,
      namely: tumor necrosis factor alpha (TNF-alpha), and interferon-gamma (IFN
      gamma), in the progression of neurologic disorders such as multiple sclerosis
      (MS) and AIDS dementia complex (ADC), with an emphasis on cytokine effects on
      glial cells. We discuss the cellular source of each cytokine within the CNS,
      their receptors, and what signaling pathways are involved in mediating their
      actions. We also describe recent findings indicating that HIV viral proteins,
      i.e., gp120, can activate cells of the CNS in a comparable manner as cytokines,
      and discuss the second messengers that mediate gp120-induced responses. We
      conclude by identifying potentially important areas of cytokine research in the
      context of neurologic disease.

PMID- 8529838
TI  - Mechanisms of phosphoryl and acyl transfer.
AB  - Acyl and phosphoryl transfer are important biochemical reactions. We have been
      using isotope effects caused by O-18, N-15, C-13, and deuterium substitution to
      examine the mechanisms and transition-state structures for enzymatic and
      nonenzymatic transfers of phosphoryl and acyl groups. Phosphoryl transfers from
      phosphate monoesters are highly dissociative, although not truly stepwise in
      protic solvents or in enzymatic reactions. Phosphodiesters show ANDN (SN2)
      reactions, whereas triester hydrolyses involve more associative transition
      states. Except under acidic conditions, true phosphorane intermediates likely
      form only when geometry requires (i.e., when the leaving group cannot be axial
      until pseudorotation of the phosphorane). Enzymatic phosphoryl transfers appear
      similar to nonenzymatic ones. The reactions of oxygen or sulfur nucleophiles with
      p-nitrophenyl acetate are concerted with a tetrahedral transition state, which is
      more dissociative with sulfur than with oxygen. Enzymatic hydrolyses of p
      nitrophenyl acetate are also concerted reactions.

PMID- 8529839
TI  - Transcription factor families: muscling in on the myogenic program.
AB  - Embryonic skeletal muscle development has become a paradigm for understanding the
      molecular basis of how cell lineages are established and how cells differentiate
      into specialized structures. Most vertebrate muscles are derived from individual
      somites that produce two distinct muscle populations: the myotomal muscles that
      generate the axial and trunk musculature and a second migratory cell population
      that colonizes regions of the developing limbs. In both instances, muscle
      differentiation is accompanied by cell cycle arrest, fusion of individual
      myoblasts into multinucleate myotubes, and the transcriptional activation of
      muscle-specific genes. Recent experimental progress has led to greater
      understanding of the molecular mechanisms that control myogenesis in the embryo.
      Most of the advances have come from the identification and isolation of
      regulatory genes that are involved in controlling specific transcriptional
      events. In particular, the muscle regulatory factor (MRF) and myocyte enhancer
      factor 2 (MEF2) families have been implicated in establishing the myogenic
      lineage as well as controlling terminal differentiation. Two additional
      transcription factors, Pax-3 and MLP, also appear to play a role in the
      production of a mature muscle cell. This review focuses on these four vertebrate
      transcription factor families and discusses the experimental evidence that these
      factors play important, non-overlapping roles in regulating skeletal muscle
      development.

PMID- 8529840
TI  - Vitronectin overrides a negative effect of TNF-alpha on astrocyte migration.
AB  - Morphogenesis and tissue repair require appropriate cross-talk between the cells
      and their surrounding milieu, which includes extracellular components and soluble
      factors, e.g., cytokines and growth factors. The present work deals with this
      communication needed for recovery after axotomy in the central nervous system
      (CNS). The failure of CNS axons to regenerate after axonal injury has been
      attributed, in part, to astrocyte failure to repopulate the injury site. The goal
      of this work was to provide an in vitro model to mimic the in vivo response of
      astrocytes to nerve injury and to find ways to modulate this response and create
      a milieu that favors astrocyte migration and repopulation of the injury site. In
      an astrocyte scratch wound model, we blocked astrocyte migration by tumor
      necrosis factor alpha (TNF-alpha). This effect could not be reversed by astrocyte
      migration-inducing factors such as transforming growth factor beta 1 (TGF-beta 1)
      or by any of the tested extracellular matrix (ECM) components (laminin and
      fibronectin) except for vitronectin (Vn). Vn, added together with TNF-alpha,
      counteracted the TNF-alpha blockage and allowed a massive migration of astrocytes
      (not due to cell proliferation) beyond that allowed by Vn only. Heparan sulfate
      proteoglycans (HSPG) were shown to be involved in the migration. The results may
      be relevant to regeneration of CNS axons, and may also provide an example that an
      extracellular component (Vn) can overcome and neutralize a negative effect of a
      growth factor/cytokine (TNF-alpha) and can act in synergy with other features of
      this cytokine to promote a necessary function (e.g., cell migration) that is
      otherwise inhibited.

PMID- 8529841
TI  - Mechanical strain-induced NO production by bone cells: a possible role in
      adaptive bone (re)modeling?
AB  - The structural competence of the skeleton is maintained by an adaptive mechanism
      in which resident bone cells respond to load-induced strains. To investigate the
      possible role of the messenger molecule nitric oxide (NO) in this response, we
      studied NO production in well-characterized organ culture systems, rat long bone
      derived osteoblast-like (LOBs) cells, and embryonic chick osteocytes (LOCYs) in
      monolayer culture. In superfused cancellous bone cores, loading (for 15 min)
      produces increases in NO2- (stable NO metabolite) release during the loading
      period, which paralleled those in PGI2 and PGE2. Loading of rat vertebrae and
      ulnae produces increases in NO2- release, and in ulnae NO synthase inhibitors
      diminish these responses. Transient rapid increases in NO release are stimulated
      by strain in both LOBs and LOCYs. Polymerase chain reaction amplification of
      extracted mRNA shows that rat ulnae, LOBs, and LOCYs express both the inducible
      and neuronal (constitutive) isoforms of NO synthase. Adaptability to mechanical
      strain relies on assessment of the strain environment followed by modification of
      bone architecture. Immediate increases in NO production induced by loading
      suggest the involvement of NO in strain measurement and cellular communication to
      establish strain distribution, as well as potentially in adaptive changes in bone
      cell behavior.

PMID- 8529842
TI  - Transgenic rabbits with the integrated human 15-lipoxygenase gene driven by a
      lysozyme promoter: macrophage-specific expression and variable positional
      specificity of the transgenic enzyme.
AB  - 15-Lipoxygenase is expressed in foamy macrophages of atherosclerotic lesions and
      has been implicated in the oxidative modification of low density lipoprotein
      during early stages of atherogenesis. To establish an animal model of 15
      lipoxygenase overexpression, we created transgenic rabbits that express at high
      level the human 15-lipoxygenase in monocyte-derived macrophages but not in liver,
      heart, kidney, lung, or other tissues. The expression level of the enzyme in
      monocyte-derived macrophages is comparable to that of interleukin 4 (IL4)-treated
      human monocytes, but more than 20-fold higher than in macrophages of normal
      rabbits. The transgenic enzyme oxygenates linoleic acid to 13S-hydroperoxy-9, 11
      (Z,E)-octadecadienoic acid (13-HODE), and arachidonic acid to a mixture of 12S
      hydroperoxy-5, 8, 10, 14 (Z,Z,E,Z)-eicosatetraenoic acid (12S-HETE), and 15S
      hydroperoxy-5, 8, 11, 14 (Z,Z,Z,E)-eicosatetraenoic acid (15S-HETE). The 12
      HETE/15-HETE ratio varied between 0.3 and 5.4, indicating a remarkable
      variability in the positional specificity of the transgenic enzyme. Macrophages
      from normal rabbits consistently produced 12S-HETE as the major oxygenation
      product. 15-Lipoxygenase-overexpressing rabbits may be used for further
      mechanistic studies on the implication of lipoxygenase in atherogenesis; they are
      also an ideal model for testing the in vivo action of 15-lipoxygenase inhibitors.

PMID- 8529843
TI  - Transient expression of calcium-independent nitric oxide synthase in blood
      vessels during brain development.
AB  - The calcium-independent nitric oxide synthase, known as NOS-II or inducible NOS,
      is only present in adult brain during pathologies that involve inflammatory
      events. We sought to establish whether NOS-II was also expressed in the course of
      normal brain development. NOS-II mRNA, measured by quantitative polymerase chain
      reaction, appeared during the perinatal period in different brain areas. It was
      detected on embryonic day 14, the earliest time analyzed, and then levels decayed
      until the first postnatal week when a second, more robust phase of expression
      arose to peak around postnatal day 7. Expression then declined to negligible
      levels in adulthood. Immunohistology revealed translation of the NOS-II protein
      in both embryonic and postnatal animals, localized to parenchymal blood vessels,
      whereas no vessel staining was detected in adults. Furthermore, NOS-II mRNA and
      enzymatic activities were present in isolated brain microvessels from developing
      animals but not from adults, and P7 vessels contained a 125 kDa protein band
      detected with a monoclonal antibody raised against rat NOS-II protein. These
      results indicate that the calcium-independent NOS mRNA and functional protein are
      transiently expressed in vessels throughout the brain in the course of normal
      development.

PMID- 8529844
TI  - A point mutation in the mitochondrial DNA of diabetes-prone BHE/cdb rats.
AB  - Mitochondrial DNA was extracted from hepatic tissue of 50- and 300-day-old male
      BHE/cdb and Sprague-Dawley rats. The complete gene for the F0ATPase subunits 6
      and 8 was sequenced. Four nucleotide substitutions were found: three of the
      substitutions were silent; the other substitution at position 523 was not. Its
      codon dictates the substitution of asparagine for aspartic acid in a critical
      location (in the polar pocket) of the F0ATPase. It is possible that this point
      mutation may explain previously reported decreases in ATP synthesis efficiency in
      BHE/cdb rats compared to Sprague-Dawley rats.

PMID- 8529846
TI  - A prediction of chromium(III) accumulation in humans from chromium dietary
      supplements.
AB  - It has been proposed that 90% of American's diets are deficient in the trace
      essential mineral chromium. Several chromium(III) dietary supplements are
      currently available to alleviate this deficiency. We show here that the same
      pharmacokinetic models that have been used to quantitate absorption of
      chromium(III) in humans predict that ingested chromium(III) will accumulate and
      be retained in human tissues for extended periods. Calculations were carried out
      with the popular supplement chromium picolinate as an example, but may be applied
      to any chromium(III) complex. Results from these calculations were compared to
      clinical data obtained from chromium(III) absorption/retention studies in humans.
      The models predict that chromium(III) can accumulate in human tissues to reach
      the levels at which DNA damage has been observed in animals and in vitro. The use
      of chromium supplements for extended periods or in excess dosages should be
      reevaluated in terms of these established models because the possible long-term
      biological effects of chromium accumulation in humans are poorly understood.

PMID- 8529847
TI  - Discovery of the reverse transcriptase.

PMID- 8529845
TI  - Chromium(III) picolinate produces chromosome damage in Chinese hamster ovary
      cells.
AB  - Chromium(III) complexes currently being sold as dietary supplements were tested
      for their ability to cause chromosomal aberrations in Chinese hamster ovary
      cells. Complexes were tested in soluble and particulate forms. Chromium
      picolinate was found to produce chromosome damage 3-fold to 18-fold above control
      levels for soluble doses of 0.050, 0.10, 0.50, and 1.0 mM after 24 h treatment.
      Particulate chromium picolinate doses of 8.0 micrograms/cm2 (corresponding to a
      0.10 mM solublized dose) and 40 micrograms/cm2 (0.50 mM) produced aberrations 4
      fold and 16-fold above control levels, respectively. Toxicity was measured as a
      decrease in plating efficiency relative to controls. The above treatments
      produced > or = 86% survival for all doses except 1.0 mM chromium picolinate,
      which produced 69 +/- 10% survival. Chromium nicotinate, nicotinic acid, and
      chromium(III) chloride hexahydrate did not produce chromosome damage at
      equivalent nontoxic doses. Damage was inferred to be caused by the picolinate
      ligand because picolinic acid in the absence of chromium was clastogenic. Data
      are evaluated in terms of their relevance to human exposure based on
      pharmacokinetic modeling of tissue accumulation and are discussed in terms of
      literature reporting toxic effects of picolinic acid.

PMID- 8529848
TI  - [Dilated cardiomyopathy: a new natural history? The experience of the Italian
      Multicenter Cardiomyopathy Study (SPIC)].
AB  - BACKGROUND: The natural history of idiopathic dilated cardiomyopathy (IDC), once
      a disease with a dire prognosis, is thought to be changing. Aim of this study was
      to describe the clinical characteristics, long term course and prognostic factors
      of IDC patients followed up prospectively since the late eighties. METHODS:
      Patients with a diagnosis of IDC confirmed by normal coronary angiography, non
      specific endomyocardial biopsy findings and a left ventricular ejection fraction
      below 50% were consecutively enrolled in a multicenter registry and followed up
      at 6-months intervals. RESULTS: From January 1986 till January 1994, 441 IDC
      patients with a mean age of 43 +/- 13 years (range 8-68) entered the registry.
      Thirty per cent of patients were women and 8% had familial dilated
      cardiomyopathy. NYHA class was I-II in 77% and 35% of patients were asymptomatic
      at the time of diagnosis. Treatment included digitalis in 235 patients (53%),
      diuretics in 239 (54%), angiotensin converting enzyme inhibitors in 269 (61%),
      betablockers in 108 (24%). Chronic atrial fibrillation was detected in 10% of
      patients and left bundle branch block in 24%. Mean cardiothoracic ratio was 0.54
      +/- 0.06. Mean left ventricular end diastolic dimension was 38 +/- 6 mm/m2; 48%
      of patients had minimal or mild left ventricular dilatation. Mean left
      ventricular ejection fraction was 30 +/- 10%. At Holter monitoring 67% of cases
      had complex ventricular arrhythmias, 37% had ventricular tachycardia and 4% had
      advanced atrioventricular block. Mean exercise stress test duration was 9 +/- 4
      minutes. After a mean follow up of 31 +/- 24 months, 337 patients were alive
      without transplantation and 5 were lost to follow up; 60 patients (14%) had died
      of cardiac causes, namely heart failure (6%), sudden death (7%) and pulmonary
      embolism (< 1%) and 30 had been transplanted (7%), while 4 had died of unclear
      causes. Survival and transplant-free survival were 94% and 90% at 2 years and 82
      and 76% at 5 years, respectively. At multivariate analysis pulmonary capillary
      wedge pressure (p = 0.0001, odds ratio, for values > 15 mm Hg, 2.05) and
      betablocker treatment (p = 0.002, odds ratio 0.26) were independent predictors of
      survival. CONCLUSIONS: In this large, multicenter prospective study, prognosis of
      IDC in the eighties appears to be improved. Early diagnosis, together with
      improved medical treatment, probably bears a causal relation to these changes.

PMID- 8529849
TI  - [Rotational atherectomy and PTCA in complex coronary lesions (B2 and C): the
      immediate and long-term results].
AB  - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) in complex
      coronary lesions (type B2 and C of the modified AHA/ACC classification) presents
      a lower primary success rate and higher risk of dissection than type A and B1
      lesions. An alternative approach to this lesions is coronary rotational ablation
      (Rotablator, Heart Technology) with complementary PTCA using low inflation
      pressures ("facilitated angioplasty"). MATERIALS AND METHODS: Twenty-six type B2
      and C lesions in 24 patients (pts) (8 female, 16 male, age 37-80 years) were
      treated with coronary rotational ablation and complementary PTCA between January
      1993 and December 1994 (4.7% of all interventional coronary procedures performed
      in this period in our laboratory). Eleven pts had stable effort angina and 13 pts
      had unstable, class IB, IIB, and IIC, angina. The treated vessel was the LAD in
      15 cases, CX in 5, RCA in 5, and an intermediate branch in one case. Coronary
      rotational ablation was proposed because of the presence of two or more risk
      factors for uneffective or complicated PTCA: eccentricity, calcified lesions,
      bifurcation stenosis, lesion length > 10 mm, severe stenosis (90-99%), ostial
      location and bend location (45-60 degrees). No lesion showed coronary thrombus,
      considered as absolute contraindication to coronary rotational ablation. We used
      small burrs (burr/artery ratio < 0.75), and complementary PTCA was performed
      using low inflation pressure (< 8 atm) and long balloons for long lesions (> 10
      mm) in order to minimize the risk of dissection. RESULTS: Coronary rotational
      ablation was successfully performed in all but two cases (24/26; 92.3%), with a
      reduction of the stenosis from 88 +/- 9% to 45 +/- 10% (range 30-60%). In two pts
      (7.7%) the procedure was complicated by acute occlusion: both pts underwent
      effective salvage PTCA with 30% residual stenosis. Small type A and B dissections
      occurred in 4/26 cases (15.4%). All but one lesions complicated by acute
      occlusion or dissection following coronary rotational ablation were not or only
      slightly calcified. Complementary PTCA was performed in all but two pts who
      already presented 30% residual stenosis after rotational ablation. A further
      reduction of stenosis to 20 +/- 9% (range 5-30%) was achieved. After
      complementary PTCA four pts (15.4%) developed type A and B dissections; in one of
      these a Palmaz-Schatz stent was implanted, whereas the remaining three pts
      presented a residual stenosis below 30% and no further procedures were
      undertaken. Overall success rate of rotational atherectomy plus salvage or
      complementary PTCA or stenting was 100%, and no major complications (Q-wave
      myocardial infarction, emergency bypass surgery or death) occurred. Three pts
      showed delayed coronary run-off (slow reflow) after rotational ablation, and two
      of these released a small amount of cardiac specific enzymes (CK MB) without ECG
      changes and wall motion alteration on echocardiographic examination. Clinical
      restenosis, defined as recurrent angina and/or positive exercise stress test,
      developed in 45.8% (11 pts); in all these pts restenosis was angiographically
      evidenced (75-99%). CONCLUSIONS: Our experience suggests that coronary rotational
      ablation along with complementary PTCA using low inflation pressure and long
      balloons is safe and effective in type B2 and C lesions if calcifications are
      present; however, restenosis rate remains high.

PMID- 8529850
TI  - [Myocardial revascularization in the patient over 70: our experience].
AB  - Since September 1985 to June 1994, 252 patients (70 years and older) underwent
      coronary artery bypass grafting isolated or combined with other surgical
      procedures. Mean age was 73 +/- 4.3 years (range: 70-84). Associated non-cardiac
      diseases were present in 131 patients (52%). Concomitant surgical procedures were
      performed in 34 patients (13.5%). Myocardial revascularization was accomplished
      under emergency conditions in 18.1% of patients. Overall operative mortality was
      5.5% (n = 14). Isolated coronary artery bypass grafting operative mortality was
      3.9% (n = 10). In-hospital death rate was higher (11.7%; n = 4) for coronary
      artery bypass grafting associated with other procedures. During the same period,
      the overall mortality rate for patients younger than 70 years was 3.4% (p = NS).
      The 30-days in-hospital mortality was significantly higher for emergency
      procedures (8.7%) than for elective surgery (4.9%) (p = 0.01). Multivariate
      stepwise logistic regression analysis identified concomitant diseases as
      independently significant risk factor. Morbidity was 36.1% (n = 91). Mean
      intensive care unit stay was 2.8 +/- 2.2 days vs 2.1 +/- 1.2 days for patients <
      70 years (p = 0.01). Total charges per case for surgical treatment were 15%
      higher for elderly patients. Follow up ranged from 1 to 108 months, averaging 32
      months. Long-term survival was 92%, 78% and 58% at 1, 5 and 10 years from
      operation. With current techniques, cardiac surgery is performed in the elderly
      with acceptable mortality and morbidity and with slightly increased average
      costs.

PMID- 8529851
TI  - Association between white blood cell count and risk factors of coronary artery
      disease.
AB  - BACKGROUND: Epidemiologic studies have shown a correlation between white blood
      cell (WBC) count and risk of developing myocardial infarction. Aim of this study
      is to assess the association between WBC and the other risk factors of coronary
      heart disease in a southern Italian population. METHODS: Baseline data for the
      1091 subjects (522 males and 569 females) enrolled in the "Montecorvino Rovella
      Project" were used to study factors associated with leukocytes. RESULTS: WBC
      count was significantly higher in smokers (8711.1 +/- 1892 cells/dl) than in ex
      smokers (6720 +/- 1608 cells/dl) and in those who never smoked (6674 +/- 1608
      cells/dl). By multiple linear regression analysis, WBC count showed a positive
      association with triglycerides (p < 0.01), cholesterol (p < 0.05) fasting glucose
      levels (p < 0.01) and diastolic blood pressure (p < 0.05). CONCLUSIONS: In this
      southern Italian population, elevated WBC count has been associated with other
      risk factors of coronary artery disease, particularly smoking, and has identified
      a high risk atherogenic profile. Even if the independency of the role of WBC is
      still under investigation, WBC count should be taken into account in establishing
      the coronary risk of apparently healthy people.

PMID- 8529852
TI  - [Mitral valve prolapse: the clinical and echocardiographic characteristics in a
      hospital outpatient population].
AB  - BACKGROUND: Mitral valve prolapse (MVP) is generally regarded as a benign
      condition, but serious complications (including severe mitral insufficiency,
      cerebral ischemia, infective endocarditis, complex arrhythmias and sudden death)
      have been described in a minority of patients and have been correlated to
      demographic, clinical and echocardiographic characteristics. Both a lack of
      standardized definition of MVP in earlier studies and the different ways of
      recruitment of MVP patients may explain the variability in reported complication
      rates. METHODS: As an offspring of a larger prospective study this paper focuses
      on the profile of patients who were found to have MVP by M-Mode and two
      dimensional echocardiography in several outpatient hospital departments. A total
      of 8252 consecutive subjects, examined since March 1990 to February 1991 in the
      Echo laboratories of the Florence area are considered; according to the presence
      or absence of structural changes (anterior mitral leaflet thickness > 5 mm,
      leaflet redundancy and/or anulus dilatation) two groups of patients with MVP (A
      and B) were identified. RESULTS: A MVP was diagnosed in 288 subjects (3.5%), 170
      females (59%) and 118 males (41%), mean age 41 +/- 18 years (range 7-84). 110
      (38%) were in Group A, 178 (62%) in Group B. The following parameters differed
      significantly in the two groups: age (45 +/- 17 vs 39 +/- 17 years; p < 0.003);
      male gender (50% vs 35%; p < 0.01); auscultatory findings (midsystolic click: 31%
      vs 68%; p < 0.00001; holosystolic murmur: 22% vs 3%; p < 0.00001); left
      ventricular diameter (53 +/- 7 vs 48 +/- 5 mm; p < 0.00001) and left atrial
      diameter (38 +/- 8 vs 33 +/- 5 mm; p < 0.00001). Among patients with mitral
      regurgitation detected by Color Doppler Echocardiography 65% were in Group A (p <
      0.00001). CONCLUSIONS: These patients with MVP are obviously selected by the
      modality of recruitment; hence there is a higher prevalence of subjects with
      morphologic abnormalities and mitral regurgitation who are older and more likely
      to be male if compared to individuals with MVP who are found in the general
      population. A long-term follow-up of these patients is ongoing: owing to the data
      of the literature about prognostic predictors, a higher incidence of
      complications with a different prognosis between the two groups (with or without
      structural changes of the mitral valve) is expected.

PMID- 8529853
TI  - [The noninvasive identification of patients with angina and normal coronary
      arteries].
AB  - BACKGROUND: Although patients with syndrome X (angina and normal coronary
      arteries, in absence of coronary spasm, cardiomyopathy or valvulopathy) and those
      with stable angina as well as documented coronary artery disease share a similar
      clinical presentation (effort related symptoms, positive exercise stress testing
      and reversible perfusion defects), their prognosis is markedly different.
      Coronary atherosclerosis is usually progressive relative to morbidity and
      mortality. Conversely prognosis both in terms of persistence of pain and
      mortality appears to be benign in syndrome X. Most cardiologists favor proceeding
      with coronary angiography in all patients presenting with exercise induced ST
      depression and reversible perfusion defects. However, it should not be assumed
      that this strategy will remain the preferred one. The aim of this study was to
      assess whether non invasive testing could identify underlying coronary artery
      anatomy, thus prognosis in the above subset of patients. The approach was
      selected on a clearly stated objective of how isosorbide dinitrate and verapamil
      may influence coronary flow reserve, thus exercise stress testing in syndrome X.
      Nitrates have been shown to reduce coronary flow reserve during stress
      tachycardia. The opposite occurs with calcium blockers. METHODS: We studied 48
      patients with effort angina referred to our laboratory for diagnostic evaluation.
      All patients underwent two separate sessions at one-day interval. Each session
      consisted of exercise stress testing before and after isosorbide dinitrate (s.l.;
      5-10 mg) or verapamil (i.v.; 10 mg), given in a randomized crossover fashion.
      Angiography was performed within 3 months from testing. Efficacy of drugs in
      terms of exercise capacity was assessed by using the following criteria: 1)
      prevention of significant (> or = 0.1 mV) ST depression while reaching same
      workload levels attained during baseline testing; 2) improvement in the ischemic
      thresholds, that is an increase in: time to 0.1 mV ST depression > or = 120 sec.,
      with heart rate (> or = 10 bpm) and rate pressure product (> or = 2 U x 1000)
      greater than those attained during baseline testing; 3) increase in time to peak
      exercise (> or = 120 sec). RESULTS: In syndrome X, both drugs resulted
      ineffective in one patient, one patient showed a favourable response to
      isosorbide dinitrate whereas the remaining 13/15 patients improved exercise
      capacity following verapamil, but not isosorbide dinitrate. The opposite occurred
      in coronary artery disease patients: both isosorbide dinitrate and verapamil were
      effective in 21/33 patients, and ineffective in 8/33 patients. The remaining 4
      patients responded to isosorbide dinitrate but not to verapamil. CONCLUSIONS: 1)
      Verapamil, but not isosorbide dinitrate, improves exercise capacity in syndrome
      X; 2) this does not apply to patients with stable angina; 3) a favourable
      response to verapamil but not to isosorbide dinitrate is both a sensitive (86%)
      and specific (100%) method for identifying patients with angina and normal
      coronary arteries; 4) non invasive testing may select those effort angina
      patients who have to proceed directly to coronary angiography; 5) some patients
      with effort related angina may not require further investigation.

PMID- 8529854
TI  - Right bundle branch block, persistent ST-segment elevation in V1-V3 and sudden
      cardiac death: always a distinct syndrome?
AB  - Right bundle branch block, persistent ST segment elevation in right precordial
      leads and sudden cardiac death, unexplainable by currently known disease, define
      a new distinct clinical and electrocardiographic syndrome. This report describe a
      patient with these features, whose physical examination, echocardiography, chest
      computed tomography and right ventricular angiography were normal. However,
      despite the negativity of these examinations, cardiac nuclear magnetic resonance
      allowed the identification of right ventricular dysplasia. Thus, right
      ventricular dysplasia should be considered in the differential diagnosis of the
      syndrome characterized by right bundle branch block, persistent ST segment
      elevation and sudden cardiac death.

PMID- 8529855
TI  - [Left ventricular function in myocardial infarct. An analysis of the prognostic
      variables in the database of the GISSI-2 study. The Researchers of GISSI-2.
      Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico].

PMID- 8529856
TI  - [The new frontier of antithrombotic therapy: ASA + warfarin, the ideal
      solution?].
AB  - In the medical literature reports are accumulating a number of case reports
      suggesting the potential efficacy and safety of the combination of low-dose
      aspirin and warfarin to improve the efficacy of antithrombotic therapy in several
      clinical conditions, ranging from unstable angina to myocardial infarction. The
      advantages deriving from such a combination have to be considered together with
      its hemorrhagic risk. Thus the efficacy of such a treatment has to be proved by
      large clinical trials before the use of this potentially dangerous therapy can be
      transferred into common clinical practice.

PMID- 8529857
TI  - [The quantification of valvular regurgitation. What new does echocardiography
      offer?].

PMID- 8529858
TI  - [Fetal echocardiography: its present and outlook].

PMID- 8529859
TI  - [Knowing how to read a scientific article. 4. Knowing how to apply a diagnostic
      test].

PMID- 8529860
TI  - [The use of informed consensus forms. Some critical reflections].

PMID- 8529861
TI  - [The MAVI study: the study of left ventricular mass in the hypertensive subject.
      The study protocol. Studio della Massa Ventricolare Sinistra nel Soggetto
      Iperteso].

PMID- 8529862
TI  - [The column of good and less good drugs. The so-called false mediator alpha
      methyldopa].

PMID- 8529863
TI  - Effect of nucleotides on thermal stability of ferricytochrome C.
AB  - The effect of nucleotides on the structure and thermal stability of
      ferricytochrome c was studied by differential scanning calorimetry. The
      association of cytochrome c with ATP and ADP resulted in a decrease in the
      denaturation temperature of cytochrome c by 7 degrees C and 4 degrees C,
      respectively, at pH 7.0. AMP did not change the denaturation temperature of
      cytochrome c at pH 7.0. The ratio between van't Hoff and calorimetric enthalpy of
      denaturation accounts for the fact that cooperative denaturation of 3-4 molecules
      of cytochrome c occurred in the presence of ATP at the pH range from 5 to 9. ADP
      gave rise to the interaction of 2-3 molecules of ferricytochrome c at pH 6-7.5,
      and AMP did not affect the interaction of protein molecules. Cytochrome c alone
      also associated at pH 7.5-10. At physiological ionic strength, pH 7.0, only ATP
      induced an association of ferricytochrome c molecules. No intermolecular
      interaction of ferricytochrome c molecules was observed at concentrations of NaCl
      higher than 0.2 mol/l not even in the presence of ATP.

PMID- 8529864
TI  - Iron ascorbate-stimulated lipid peroxidation in vitro. Why is the method
      controversial?
AB  - In vitro generation of thiobarbituric acid reactive substances (TBARS) is
      frequently used to assess organ susceptibility to lipid peroxidation. The yield
      of TBARS is severalfold enhanced by an addition of iron ions with reductors or
      chelators such as ascorbate, NADPH, ADP or pyrophosphate. The process cannot be
      interpreted in a simple way, since it involves several enzymatic and nonenzymatic
      reactions. There are no clear interpretations of the ambiguous effects of
      denaturating factors and chelating agents on TBARS generation. Also controversy
      arises from the curvilinear relationship between the homogenate concentration and
      the yield of TBARS. This has been modelled in the present work by combining two
      functions describing the sequential reaction with two limiting steps. One of them
      is related to catalytic action of iron and ascorbate, while the other to an
      enzyme, possibly phospholipase A2, as has been suggested by some investigators.
      Two models should be considered since it is impossible to decide which kinetic
      equation should predominate in the model. Nevertheless, the model reflects
      kinetic properties of the process. The effects of catalyst concentration and some
      other modification upon the yield of TBARS were also investigated experimentally.
      The results of experiments and modelling showed that the analytical procedures
      used by investigators need standardisation as the results obtained under a
      variety of procedures may reflect quite different properties of the living
      systems.

PMID- 8529865
TI  - Peroxidase-activated carcinogenic azo dye Sudan I (Solvent Yellow 14) binds to
      guanosine in transfer ribonucleic acid.
AB  - Peroxidase in the presence of hydrogen peroxide catalyzes in vitro the activation
      of the carcinogenic azo dye Sudan I (1-phenylazo-2-hydroxynaphthalen) to tRNA-,
      homopolyribonucleotide- and 5'-monophosphate nucleoside-bound products. tRNA,
      poly G and guanosine 5'-monophosphate modified by activated Sudan I become
      colored and have an absorption maximum of approx. 480 nm. Cochromatographic
      analysis of adducts obtained by a reaction with tRNA and guanosine 5'
      monophosphate on a thin layer of cellulose showed that the major Sudan I-tRNA
      adduct was formed by a reaction of activated Sudan I with guanosine in tRNA. The
      radical mechanism of the binding of the Sudan I molecule, containing the whole
      azo aromatic system, to nucleic acids is discussed.

PMID- 8529866
TI  - Involvement of different Ca2+ sources in changes of responsiveness of guinea-pig
      trachea to repeated administration of histamine and acetylcholine.
AB  - The role of Ca(i) and Ca(o) in changes of responsiveness of guinea pig tracheal
      smooth muscle strips to repeated applications of histamine and acetylcholine was
      investigated. Homologous desensitization to histamine developed when the airways
      were exposed to concentrations higher than 10(-5) mol/l, while sensitization to
      acetylcholine was recorded even when its highest concentration did not exceed 10(
      5) mol/l. The maximum of the concentration response curves (CRC) was reduced upon
      repeated histamine, and enhanced upon repeated acetylcholine administration.
      There was, however, no significant difference in EC50 values for repeated CRCs of
      the stimulants. In Ca2+ free, EGTA (10(-4) mol/l) containing solution the second
      contraction elicited by single (10(-3) mol/l) or cumulative (10(-9)-10(-3) mol/l)
      histamine application was significantly smaller, while that elicited by
      acetylcholine did not differ significantly from the first one. In Ca(2+)-free,
      caffeine (10(-2) mol/l) and EGTA containing solution the contractile responses to
      repeated additions of Ca2+ (2.7 mmol/l) in histamine and acetylcholine (10(-3)
      mol/l) treated tracheae was decreased and unchanged, respectively. Addition of
      nifedipine (10(-6) mol/l) to this solution fully prevented Ca2+ in inducing
      contraction in histamine treated tracheae, while Ca2+ still induced contraction
      in acetylcholine treated tracheae. TMB-8 (10(-5) mol/l) was ineffective in
      blocking the remaining acetylcholine induced contractions. The present data
      suggest that contractions of the guinea pig trachea elicited by histamine and
      acetylcholine are due to release of intracellular Ca2+ from a caffeine sensitive
      store and to influx of Ca2+ from the extracellular space via voltage operated
      channels (VOC). Moreover, acetylcholine activated Ca2+ entry into guinea pig
      tracheal smooth muscle cells via the nifedipine insensitive mechanism, probably
      receptor operated channels (ROC). It is concluded that desensitization to
      histamine in the guinea pig trachea is most probably due to alterations in
      intracellular Ca2+ mobilization and Ca2+ influx via VOC. In contrast,
      sensitization to acetylcholine involved primarily enhanced Ca2+ influx via VOC
      and Ca2+ induced Ca2+ release.

PMID- 8529867
TI  - Local anesthetic [2-(decyloxy)phenyl]-2-(1-piperidinyl)ethyl ester of carbamic
      acid perturbs phosphatidylcholine bilayer.
AB  - Monohydrochloride of [2-(decyloxy)phenyl]-2-(1-piperidinyl)ethyl ester of
      carbamic acid (C10A) has a biphasic effect on the fluidity of egg yolk
      phosphatidylcholine (EYPC) model membranes as detected by the methyl ester of
      stearic acid spin probe, with the paramagnetic doxyl group bound to C-16. The
      fluidity increases up to a molar ratio of C10A:EYPC = 0.5 with a subsequent
      decrease. This decrease in fluidity may be due to interdigitation of hydrocarbon
      chains in the bilayer.

PMID- 8529868
TI  - A simple method of determination of partition coefficient for biologically active
      molecules.
AB  - A simple method is presented for the determination of partition coefficient of an
      effector between water environment and biological material, based on
      concentration-dependent effects. The method allows the determination of partition
      coefficients for biological objects such as algae, bacteria and other
      microorganisms.

PMID- 8529869
TI  - New tools for integrated genetic and physical analyses of the Escherichia coli
      chromosome.
AB  - Genetic and biophysical techniques have traditionally been applied to genome
      mapping independently of one another. We present a series of Escherichia coli
      mini-Tn10 insertions that contain the rare-cutting polylinker 1 (RCP1) of rare
      restriction sites [including BlnI/AvrII, SpeI, NheI, XbaI, NotI, PacI and SfiI;
      Mahillon and Kleckner, Gene 116 (1992) 69-74] which allows them to be used not
      just for genetic mapping, but also for rapid physical mapping and integrated
      physical and genetic mapping of the E. coli chromosome. Their isolation and their
      physical and genetic coordinates in K-12 strain MG1655 are presented. Also, their
      use in purifying insertion-delimited DNAs from E. coli K-12 and in
      macrorestriction mapping of a pathogenic strain's chromosome is demonstrated.
      These insertions allow integration of (i) different macrorestriction patterns of
      a single strain's chromosome, (ii) the physical map of a single strain's
      chromosome with the genetic map of the species, and (iii) the physical maps of
      different strains' chromosomes.

PMID- 8529870
TI  - Construction of a translational lacZ fusion system to study gene regulation in
      Neisseria gonorrhoeae.
AB  - A translational lacZ reporter system to study gene regulation in Neisseria
      gonorrhoeae (Ng) was developed. The pUC18-based vector pLES94 transforms Ng and
      recombines into the Ng chromosome at the site of the proAB genes. The vector
      contains a restriction site for cloning promoters that will result in a lacZ gene
      fusion. Initial cloning and characterization of promoters can be done in
      Escherichia coli. The vector contains both ApR and CmR genes, however the ApR
      gene is lost when the insert combines into the Ng chromosome. This system gives
      single copy expression of the fusion and does not result in the inactivation of
      the gene of interest.

PMID- 8529871
TI  - Identification of epidemiologic markers for Neisseria meningitidis using
      difference analysis.
AB  - The feasibility of identifying epidemiologic markers based solely on the
      identification of DNA fragments present in outbreak-associated isolates was
      investigated using Neisseria meningitidis (Nm) as a model system. The clonal
      structure of Nm has been well characterized using multilocus electrophoresis. In
      Canada, electrophoretic types ET1, ET5, ET9 and ET21 are being displaced from the
      natural population by type ET15, and the latter type is associated with an
      increased prevalence of serogroup C meningococcal disease. Difference analysis,
      which uses subtractive hybridization and polymerase chain reaction (PCR)
      amplification, was employed to identify amplifiable DNA fragments (amplicons)
      that differ between the ET15 and the ET1, ET5, ET9 and ET21 genomes. 14 amplicons
      were cloned which were further characterized by Southern blot analysis to
      identify six amplicons that represent fragments either unique to or highly
      polymorphic in the ET15 genome. Oligodeoxyribonucleotide primer pairs were
      designed for each of the six amplicons, and PCR amplification was used to
      determine their prevalence across a panel of 167 Nm isolates representative of
      other serogroups and ETs. Among group C isolates only two of the six amplicons,
      designated as A and G, were effective in discriminating ET15 from non-ET15
      isolates. Amplicon A detects a deletion in the dhps gene which effectively
      differentiates sulfonamide-sensitive and -resistant serogroup C isolates. The
      frequency of amplicon A and G detection in the other serogroups and ETs was too
      great to facilitate their direct use as diagnostic markers for the
      differentiation of virulent Nm isolates.

PMID- 8529872
TI  - A new gene, cbl, encoding a member of the LysR family of transcriptional
      regulators belongs to Escherichia coli cys regulon.
AB  - The cbl (cysB-like) gene has been identified in Escherichia coli. The analysis of
      the cloned cbl sequence revealed strict homology to an ORF of unknown function
      found initially in Klebsiella aerogenes [Schwacha and Bender, J. Bacteriol. 175
      (1993) 2107-2115]. The predicted Cbl protein has structural features of the LysR
      family of transcriptional activators. It is also strongly similar to the CysB
      protein, the activator of the cys regulon. The position of cbl on the Ec physical
      map has been established at a 2070-kb (43.5 min) region between asnU and asnV.
      The gene is expressed in vivo as a 1-kb monocistronic transcript starting from
      one major transcription start point. Unexpectedly, the in vivo expression of cbl
      has shown dependence on CysB, belonging to the same family of proteins. The
      promoter region of cbl binds purified CysB protein in a manner similar to other
      CysB-responsive promoters. A cbl disruption mutant was constructed by insertion
      of a KmR gene cartridge into the ORF on the chromosome. Phenotypes related to cbl
      expression suggest the involvement of the gene in an accessory regulatory circuit
      within the cys regulon engaging, in the last step, the function of the cysM gene
      encoding O-acetylserine (thiol)-lyase B.

PMID- 8529873
TI  - Repeated sequences isolated from Bordetella pertussis induce DNA rearrangements
      and deletions at high frequency.
AB  - Two repeated sequences (RS) from Bordetella pertussis were cloned in Escherichia
      coli and sequenced. The RS, called RSBP1 and RSBP3, are highly homologous to
      other B. pertussis RS. The recombinant plasmids containing RSBP1 and RSBP3 or
      transposon-like structures of these elements were not stable but segregated
      plasmids with deletions or rearranged DNA. RS of B. pertussis seem to be able to
      stimulate both intra- and inter-genomic RecA-independent recombination events. In
      at least one case, the observed deletion had occurred precisely between the RS
      terminus and a site with sequence homology to the terminus. The high frequency
      rearrangements associated with the RS imply that the RS are transposable
      elements.

PMID- 8529874
TI  - Cloning and sequence analysis of the Corynebacterium diphtheriae dtxR homologue
      from Streptomyces lividans and S. pilosus encoding a putative iron repressor
      protein.
AB  - The iron-regulated promoter involved in desferrioxamine B synthesis of
      Streptomyces pilosus contains a region homologous to the iron repressor (DtxR)
      binding site of the diphtheria toxin gene promoter in Corynebacterium diphtheriae
      [Gunter et al., J. Bacteriol. 175 (1993) 3295-3302]. Here, we report the cloning
      and sequencing of the putative Streptomyces iron repressor gene, homologous to
      dtxR of C. diphtheriae. The N-terminal 139 amino acids of the deduced protein are
      73% identical to DtxR.

PMID- 8529875
TI  - Identification of Streptomyces olivaceus Tu 2353 genes involved in the production
      of the polyketide elloramycin.
AB  - The genes for the production of elloramycin (ELM) from Streptomyces olivaceus
      (So) Tu2353 were cloned using a polyketide synthase gene probe from the
      tetracenomycin pathway. A cosmid clone (16F4) isolated from a gene library of So
      Tu2353 conferred tetracenomycin C and ELM resistance to S. lividans TK64 and
      complemented a mutation in So Tu2353R. Introduction of cosmid 16F4 into S.
      lividans TK64 resulted in the production of 8-demethyl-tetracenomycin C, an
      intermediate of ELM biosynthesis.

PMID- 8529876
TI  - Cloning, sequencing and expression of the ilvBNC gene cluster from Streptomyces
      avermitilis.
AB  - The metabolism of the branched-chain amino acids (BCAA) isoleucine, leucine and
      valine is correlated to the production of polyketide antibiotics in many
      streptomycetes. Despite its significance, this biosynthetic pathway is poorly
      understood in Streptomyces. In order to develop a better understanding of
      Streptomyces BCCA biosynthesis, two genes, ilvBN and ilvC, encoding acetohydroxy
      acid synthase (AHS) and acetohydroxy acid isomeroreductase (IR), respectively,
      were cloned from Streptomyces avermitilis, a strain producing avermectins, potent
      antiparasitic compounds. The genes were isolated by applying a combination of PCR
      and genomic library screening. The deduced amino-acid sequences revealed
      significant homology to the AHS and IR proteins from other bacterial species. The
      ilvBN gene, expressed in Escherichia coli (Ec) by using the expression vector
      pGEX-4T-1, complemented the ilv- mutation of Ec PS1283. Ec transformants produced
      high levels of AHS, whose activity was feedback inhibited by valine.

PMID- 8529877
TI  - Construction of thiostrepton-inducible, high-copy-number expression vectors for
      use in Streptomyces spp.
AB  - A high-copy-number plasmid expression vector (pIJ6021) was constructed that
      contains a thiostrepton-inducible promoter, PtipA, from Streptomyces lividans 66.
      The promoter and ribosome-binding site of tipA lie immediately upstream from a
      multiple cloning site (MCS) which begins with a NdeI site (5'-CATATG) that
      includes the tipA translational start codon (ATG), allowing the synthesis of
      native proteins. Transcriptional terminators occur just upstream from PtipA and
      immediately downstream from the MCS. To demonstrate the utility of pIJ6021, two
      streptomycete genes and a growth hormone-encoding gene from flounder
      (Paralichthys olivaceus) were cloned in the vector and expressed in S. lividans
      or S. coelicolor A3(2). A derivative of pIJ6021, pIJ4123, has a unique NdeI site
      positioned downstream from a nucleotide sequence that encodes a His6 sequence and
      thrombin cleavage site. pIJ4123 can be used to produce His-tagged fusion proteins
      that can be readily purified by Ni(2+)-affinity chromatography; if necessary, the
      His6 tag can be removed by digestion with thrombin. The vectors contain a
      kanamycin-resistance-encoding gene for the selection of transformants.

PMID- 8529878
TI  - An abnormally acidic TATA-binding protein from a hyperthermophilic archaeon.
AB  - The gene encoding the TATA-binding protein (PkTBP) from a hyperthermophilic
      archaeon, Pyrococcus sp. KOD1 (Pk), was cloned and sequenced. An open reading
      frame with homology to the conserved C-terminal core region of eukaryotic TBP was
      expressed in Escherichia coli. Specific DNA-binding activity of the recombinant
      PkTBP (190 amino acids, 21.36 kDa) was also demonstrated. Although it was
      composed of a structurally direct repeat sequence which is similar to eukaryotic
      TBP, the total net charge of archaeal TBP was amazingly negative (calculated
      isoelectric point (pI) was 4.66 and experimentally estimated pI was 4.8). A
      series of five Glu residues was found at the C terminus of archaeal TBP. These
      data strongly suggest that a positively charged protein is also involved in the
      transcription initiation event which might stabilize the structure of the genomic
      DNA under high-growth-temperature conditions.

PMID- 8529879
TI  - The relationship between mRNA half-life and gene function in the yeast
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae (Sc) mRNAs have been described as falling into two major
      classes with respect to mRNA half-life [Santiago et al., Nucleic Acids Res. 14
      (1986) 8347-8360]. We have used DNA sequence analysis to address the functional
      roles of eleven of the thirteen cDNAs upon which Santiago et al. based their
      conclusions. Eight had been described as copies of short half-life and five as
      copies of long-half-life mRNAs. We show here that five members of the short-half
      life class encode known Sc cytosolic ribosomal proteins (rp). One further short
      half-life cDNA appears to encode a new Sc rp related to higher eukaryotic rp S12.
      Among the long-half-life cDNAs, one encodes the glucose-inducible glycolytic
      enzyme enolase, while another is related to the mouse housekeeping gene MER5.

PMID- 8529880
TI  - ROK1, a high-copy-number plasmid suppressor of kem1, encodes a putative ATP
      dependent RNA helicase in Saccharomyces cerevisiae.
AB  - The KEM1 gene is involved in nuclear fusion during conjugation, and chromosome
      transmission and spindle pole body duplication/or separation during mitotic cell
      division in the yeast Saccharomyces cerevisiae. KEM1 was also independently
      identified as DST2, SEP1, XRN1 and RAR5 on the basis of DNA strand transferase or
      exoribonuclease activity in vitro or mutations affecting plasmid stability. To
      understand the various functions suggested for KEM1 and to identify other genes
      with functions similar or related to those of KEM1, we have characterized the
      ROK1 gene which was isolated as a high-copy-number plasmid suppressor of the kem1
      null mutation. Sequence analysis of the smallest subclone with the suppression
      activity revealed an open reading frame of 564 amino acids. The ROK1 aa sequence
      contains highly conserved domains found in the DEAD protein family of ATP
      dependent RNA helicases. ROK1 is essential for viability and is closely linked to
      KEM1 on chromosome VII.

PMID- 8529881
TI  - Identification of Schizosaccharomyces pombe gene psk1+, encoding a novel putative
      serine/threonine protein kinase, whose mutation conferred resistance to
      phenylarsine oxide.
AB  - We have identified a novel putative protein kinase-encoding gene from
      Schizosaccharomyces pombe (Sp), designated psk1+, by using a highly conserved
      amino acid (aa) sequence motif to design amplification of DNA fragments using
      PCR. The putative translation product of psk1+ contains 436 aa, with a molecular
      mass of 49,317 Da. A single psk1+ was identified by genomic Southern blot
      analysis, and the genomic mapping indicated that psk1+ was localized in Sp
      chromosome III. Growth of wild-type Sp cells was inhibited by 0.5 microM
      phenylarsine oxide, a protein tyrosine phosphatase inhibitor, but psk1- cells
      were relatively resistant to this drug.

PMID- 8529882
TI  - Cloning and characterisation of a gene encoding a cuticle-degrading protease from
      the insect pathogenic fungus Metarhizium anisopliae.
AB  - Metarhizium anisophilae (Ma) secretes a range of proteases when grown in vitro on
      insect cuticle. A trypsin-like serine protease, PR2, was purified from culture
      filtrates by anion exchange chromatography and the N-terminal sequence
      determined. Using oligodeoxyribonucleotide probes based on this sequence and that
      of the highly conserved trypsin active site, a gene was isolated from a lambda
      EMBL3 genomic library of Ma isolate ME1. Sequencing of the gene and RT-PCR
      revealed that the gene contains two introns which are 94 and 40 bp long. The
      deduced protein consists of 254 amino acids, has a putative signal sequence to
      allow transport into the endoplasmic reticulum and probably undergoes a second
      proteolytic processing step at its N terminus to yield the mature enzyme. The
      putative mature enzyme has extensive homology with other serine proteases of the
      trypsin subclass and, in particular, with the trypsin characterised from Fusarium
      oxysporum.

PMID- 8529883
TI  - Minisatellites corresponding to the human polycore probes 33.6 and 33.15 in the
      genome of the most 'primitive' known eukaryote Giardia lamblia.
AB  - DNA fingerprinting has been widely used for genetic characterization and
      individual recognition in a range of species, from man and other mammals down the
      evolutionary scale to some lower eukaryotic parasites. These techniques utilise
      repetitive elements first characterised in the human genome, known as
      minisatellites, which display extensive allelic variability. Few biological or
      biochemical characteristics have been found that distinguish isolates of Giardia
      lamblia (Gl), or their apparent variations in virulence. We have characterized 21
      Gl isolates in axenic culture using DNA fingerprinting with the human
      minisatellite probes, 33.6 and 33.15. Up to 12 variable bands per isolate were
      recognized in the size range of 2.5 to 15 kb by Southern blot hybridization of
      restriction endonuclease-digested Gl DNA. Most isolates demonstrated a distinct
      banding pattern or DNA fingerprint. The results suggest that this method may
      provide a basis for the detailed genotypic characterization of Gl which will be
      amenable to computer and statistical analysis for use in studies of virulence and
      epidemiology. Also, as Gl occupies a unique phylogenetic position as a member of
      the earliest known divergence from the eukaryotic line of descent, this study may
      provide a useful model for the study of other important eukaryotic pathogens, as
      it is rapidly becoming apparent that minisatellites are ubiquitous components of
      eukaryotic genomes.

PMID- 8529884
TI  - Multiple cloning sites carrying loxP and FRT recognition sites for the Cre and
      Flp site-specific recombinases.
AB  - Plasmids were constructed carrying the loxP and FRT recognition sites for the Cre
      and Flp site-specific recombinases, respectively, within multiple cloning sites.
      Vectors carrying single and tandemly repeated targets are available with various
      flanking restriction enzyme sites. In addition, a series of plasmids carrying
      both loxP and FRT sites is available. These vectors facilitate construction of
      target molecules for these site-specific recombinases which are becoming
      increasingly important tools for the in vivo manipulation of DNA.

PMID- 8529885
TI  - Four new derivatives of the broad-host-range cloning vector pBBR1MCS, carrying
      different antibiotic-resistance cassettes.
AB  - Four new antibiotic-resistant derivatives of the broad-host-range (bhr) cloning
      vector pBBR1MCS have been constructed. These new plasmids have several advantages
      over many of the currently available bhr vectors in that: (i) they are relatively
      small (< 5.3 kb), (ii) they possess an extended multiple cloning site (MCS),
      (iii) they allow direct selection of recombinant plasmid molecules in Escherichia
      coli via disruption of the LacZ alpha peptide, (iv) they are mobilizable when the
      RK2 transfer functions are provided in trans and (v) they are compatible with
      IncP, IncQ and IncW group plasmids, as well as with ColE1- and P15a-based
      replicons.

PMID- 8529886
TI  - Escherichia coli expression vectors containing a protein kinase recognition
      motif, His6-tag and hemagglutinin epitope.
AB  - Escherichia coli expression vectors, based on the pET system, were constructed to
      allow fusion of a protein kinase (PK) recognition motif, a hemagglutinin (HG)
      epitope-tag and a His6-tag at the N-terminal portion of a protein of interest.
      The fusion proteins, that result from expression using these vectors, can be
      phosphorylated in vitro using cAMP-dependent PK, immunoprecipitated using
      monoclonal antibody against the HG-epitope, and can be rapidly purified using a
      Ni2+ column.

PMID- 8529887
TI  - Cloning and sequence of the groESL heat-shock operon of Pasteurella multocida.
AB  - By using degenerate oligodeoxyribonucleotide primers for conserved regions of
      groEL, a 0.6-kb fragment of Pasteurella multocida genomic DNA was amplified using
      PCR. The amplified fragment was then used as a probe to isolate a genomic
      fragment containing the entire GroESL operon. The isolated genomic fragment was
      found to contain two open reading frames, the sequences of which were highly
      homologous to the prokaryotic groES and groEL families of genes.

PMID- 8529888
TI  - Color selection with a hygromycin-resistance-based Escherichia coli-mycobacterial
      shuttle vector.
AB  - Hygromycin-resistance (HyR)-based Escherichia coli-mycobacterial shuttle plasmids
      have high efficiencies of transformation and a broad mycobacterial host range. We
      have introduced a lacZ alpha (encoding the alpha-polypeptide fragment of beta
      galactosidase (beta Gal))-multiple cloning site cassette into a HyR-based shuttle
      vector to generate a plasmid with nine unique cloning sites and the added feature
      of beta Gal color selection in appropriate E. coli host strains.

PMID- 8529889
TI  - A novel transcribed repeat element from Entamoeba histolytica.
AB  - We have identified an unusual 0.55-kb DNA repeat element specific to Entamoeba
      histolytica (Eh) which we call interspersed element (IE). The IE is a common
      feature in independently isolated genomic and cDNA fragments. Hybridization of
      labeled IE sequences to trophozoite DNA, RNA and first-strand cDNA prepared from
      poly(A)-enriched mRNA indicate that the IE are reiterated about 500 times per Eh
      trophozoite and that one or more can be found as RNA transcripts. These features
      and the degree of conservation of IE suggest a possible role for these sequences.

PMID- 8529890
TI  - A putative pathway for biosynthesis of the O-antigen component, 3-deoxy-L-glycero
      tetronic acid, based on the sequence of the Vibrio cholerae O1 rfb region.
AB  - The nucleotide sequence of a region of the rfb genes, encoding biosynthesis of
      the Vibrio cholerae (Vc) O1 O-antigen, was determined. Analysis of the open
      reading frames (ORFs) within this region has revealed similarities with a number
      of different classes of biosynthetic proteins and enzymes. The ORFs have been
      designated RfbK, RfbL, RfbM, RfbN and RfbO. RfbK is a small, acidic protein which
      has similarity to the family of proteins known as acyl-carrier proteins (ACP).
      The RfbL protein has similarity to a super-family of enzymes which adenylate
      their substrates as a part of their reaction mechanism. Included in these are
      several acetyl-CoA ligases. Alignment of RfbL with these proteins reveals a
      highly conserved domain containing the motif GlyXaaXaaGlyXaaPro. This resembles
      the ATP-binding site motif and may represent a variant of the usual motif, except
      that Pro replaces Gly. The VcRfbM protein has similarity with a family of long
      chain, iron-containing alcohol dehydrogenases, of which the Escherichia coli K-12
      fucO and adhE gene products are also members. The RfbN protein has sequence
      homology with LuxE and LuxC of Vibrio harveyi (Vh) and other bioluminescent
      bacterial species. The latter are two components of the enzyme complex which
      synthesizes the long-chain aldehyde used in the V. harveyi bioluminescence
      system. Finally, the VcRfbO protein has sequence similarity with acetyl-CoA
      transferases. We were able to identify a number of the gene products using a T7
      expression system, confirming several of the allocated ORFs. A biosynthetic
      pathway for the Vc O-antigen component 3-deoxy-L-glycero-tetronic acid, based on
      the enzymatic functions predicted for the RfbK, RfbL, RfbM, RfbN and RfbO
      proteins, is presented.

PMID- 8529891
TI  - A putative pathway for perosamine biosynthesis is the first function encoded
      within the rfb region of Vibrio cholerae O1.
AB  - The first four genes (rfbA,B,D,E) of the rfb region of Vibrio cholerae O1 are
      predicted to encode the enzymes required for the biosynthesis of perosamine,
      which constitutes the backbone structure of the O-antigen of the
      lipopolysaccharide. Based on homology to known proteins/protein families, the
      following functions are predicted: RfbA, phosphomannose isomerase-guanosine
      diphosphomannose pyrophosphorylase; RfbB, phosphomanno-mutase; RfbD, oxido
      reductase and RfbE, perosamine synthetase (amino-transferase). Thus, perosamine
      is synthesized from fructose 6-phosphate via the intermediates mannose 6
      phosphate by RfbA, to mannose 1-phosphate by RfbB, to GDP-mannose by RfbA, to GDP
      4-keto-6-dideoxymannose by RfbD and to GDP-perosamine by RfbE. This final product
      would then serve as the substrate for the addition of the tetronate, which could
      then be polymerized into the O-antigen for transfer to the lipid A plus core
      oligosaccharide and export to the cell surface. The organization of these genes
      are such that one would expect them to be translationally coupled as part of the
      rfb operon. However, the absence of readily detectable promoter sequences
      suggests low levels of transcription, in line with other studies. The nucleotide
      sequence of these genes is absolutely conserved in the two isolates 569B
      (classical, Inaba) and O17 (El Tor, Ogawa) which were expected to show maximal
      sequence variation. This suggests very tight constraints on the micro-evolution
      within these sequences.

PMID- 8529892
TI  - Regulation of tcp genes in classical and El Tor strains of Vibrio cholerae O1.
AB  - Expression of genes encoding the toxin-co-regulated pilus (TCP) varies between
      the two biotypes of Vibrio cholerae O1. Sequence analysis of the tcp locus from
      the classical and El Tor strains has revealed differences in the intergenic
      regions between tcpI and tcpP, and tcpH and tcpA, which may be involved in
      regulation. To investigate this possibility, transcription of tcpA, and the
      predicted upstream promoters for tcpI and tcpP, has been analysed in the
      classical and El Tor strains using promoter-cat (chloramphenicol
      acetyltransferase) fusions. Together with primer extension analyses, these
      studies indicate that the tcpA and tcpP promoters are toxR-dependent and suggest
      that TcpP may be involved in activation of both the tcpI and tcpP promoters. We
      conclude that differences in the level of tcpA expression in a classical and an
      El Tor strain are likely to be due to the effect of sequence variation on the
      ability of control factors to act on these regulatory regions.

PMID- 8529893
TI  - Clavulanic acid biosynthesis in Streptomyces clavuligerus: gene cloning and
      characterization.
AB  - Seven classes of Streptomyces clavuligerus mutants defective in clavulanic acid
      (CLA) biosynthesis have been identified and used to clone the chromosomal DNA
      encoding eight CLA biosynthetic genes. The complete sequences of three and the
      partial sequences of two of these biosynthetic genes are reported, together with
      their known or predicted functions.

PMID- 8529894
TI  - Identification and sequences of the Treponema pallidum fliM', fliY, fliP, fliQ,
      fliR and flhB' genes.
AB  - Information regarding the biology and virulence attributes of Treponema pallidum
      (Tp) is limited due to the lack of genetic exchange mechanisms and the inability
      to continuously cultivate this spirochete. We have utilized TnphoA mutagenesis of
      a Tp genomic DNA library in Escherichia coli (Ec) to identify genes encoding
      exported proteins, a subset of which are likely to be important in treponemal
      pathogenesis. We report here the identification and nucleotide (nt) sequence of a
      5-kb treponemal DNA insert that contains seven open reading frames (ORFs). The
      proteins encoded by six of these ORFs have homology with members of a newly
      described protein family involved in the biogenesis/assembly of flagella and the
      control of flagellar rotation in Ec, Salmonella typhimurium (St) and Bacillus
      subtilis (Bs). Certain members of this family are also involved in the export of
      virulence factors in Yersinia (Yr) spp., St and Shigella flexneri (Sf). We have
      named these six ORFs fliM', fliY, fliP, fliQ, fliR and flhB'. The operon
      containing these ORFs has been designated as the fla operon. We hypothesize that
      the protein products of these genes are involved in the biogenesis/assembly of
      flagella and the control of flagellar rotation in Tp.

PMID- 8529895
TI  - Cloning, sequence analysis and expression in yeasts of a cDNA containing a
      Lipomyces kononenkoae alpha-amylase-encoding gene.
AB  - The yeast Lipomyces kononenkoae (Lk) secretes a highly active raw starch
      degrading alpha-amylase (alpha Amy) that liberates reducing groups from glucose
      polymers containing both alpha-1,4 and alpha-1,6 bonds. The LKA1 gene encoding
      this industrially important alpha Amy was cloned as a 2261-bp cDNA fragment from
      a glucose-derepressed mutant (IGC4052B) of Lk and characterized. The nucleotide
      (nt) sequence of the cDNA fragment was determined, revealing an open reading
      frame of 1872 bp, encoding a 596 amino-acid (aa) mature protein (LKA1) with a
      calculated M(r) of 65,706. The similarity between the aa sequence of LKA1 and
      those of other alpha Amy showed four common conserved regions characteristic of
      the alpha Amy protein family: (A) 264DIVVNH269, (B) 349GLRIDTVKH357, (B')
      376GEVFD380 and (C) 439FLENQD444. The deduced aa sequence revealed significant
      homology to the aa sequences of the Aspergillus oryzae, Schwanniomyces
      occidentalis and Saccharomycopsis fibuligera alpha Amy, various bacterial
      cyclomaltodextrin glucanotransferases, a beta-amylase and the 5'-region of a
      glucoamylase. LKA1 was expressed in Saccharomyces cerevisiae (Sc) under the
      control of the phosphoglycerate kinase (PGK1) promoter and Northern blot analysis
      showed the presence of a single 2.3-kb transcript. The 28-aa signal peptide of
      the LKA1 protein efficiently directed its secretion into the medium when
      expressed in Sc.

PMID- 8529896
TI  - Sequence of the Escherichia coli C homoprotocatechuic acid degradative operon
      completed with that of the 2,4-dihydroxyhept-2-ene-1,7-dioic acid aldolase
      encoding gene (hpcH).
AB  - The homoprotocatechuic acid (HPC) pathway is a typical catabolic sequence for
      converting peripheral metabolites into intermediates of central metabolism. How
      the pathway enzymes that catalyse such natural sequences have arisen is as yet
      uncertain, but the explanation is likely to be of interest in devising pathways
      to catabolise the man-made chemicals that are increasingly found in the
      environment. The nucleotide (nt) sequence of the Escherichia coli C 2,4
      dihydroxyhept-2-ene-1,7-dioic acid (HHED) aldolase-encoding gene (hpcH) reported
      here completes the sequencing of the HPC pathway genes, and so makes it possible
      to assess the relatedness of all the pathway enzymes. There were no striking
      amino acid (aa) sequence identities between any of the pathway enzymes,
      suggesting that they had not arisen by duplication of an ancestral gene, with
      subsequent divergence. The HHED aldolase showed no striking identity (16-22%)
      with the aldolases from five other bacteria catalysing the analogous reaction in
      the catechol meta-fission pathway. However, there was significant aa identity
      (47.8%) with an E. coli K-12 open reading frame (ORF) of as yet unknown function,
      suggesting that this ORF may encode an aldolase of some kind.

PMID- 8529897
TI  - Cloning and comparison of mercury- and organomercurial-resistance determinants
      from a Pseudomonas stutzeri plasmid.
AB  - Plasmid pPB confers broad-spectrum mercury resistance (HgR) to a Pseudomonas
      stutzeri strain. Two pPB regions, separated by 25-30 kb and sharing homology with
      Tn501 mer (Hg detoxification) genes, were cloned separately and each was shown to
      carry a cluster of functional and independently regulated mer genes. One of the
      two gene clusters conferred resistance only to inorganic mercury, and had a
      structure identical to the classical model of narrow-spectrum mer operons. In the
      other cluster a novel merB gene, not homologous to the other known merB, but with
      the same function, was mapped upstream from merA, interposed between an
      organomercurial-responsive regulatory element and transport genes. Evidence
      suggests that merB and the other structural mer genes might be transcribed from
      two distinct promoters. The presence of two inverted repeat-like elements,
      identical to those of Tn5053, upstream from merR suggests that the pPB broad
      spectrum-gene cluster could be part of a transposon-like element.

PMID- 8529898
TI  - An open reading frame in the approximately 28-kb tox-argk gene cluster encodes a
      polypeptide with homology to fatty acid desaturases.
AB  - Part of an apparent open reading frame in the tox-argK gene cluster of
      Pseudomonas syringae pathovar phaseolicola (Psp) potentially encodes a
      polypeptide with sequence similarity to fatty acid desaturases (DES). Escherichia
      coli B expressing this segment under T7 promoter control produced a 34-kDa
      polypeptide. The possible involvement of a DES in facilitating phaseolotoxin
      (Ptx) secretion at the low temperatures normally required for its synthesis and
      the evolutionary implications about the origin of the tox-argK gene cluster are
      discussed.

PMID- 8529899
TI  - Cloning and sequencing of the membrane-bound hydrogenase-encoding genes (hupS and
      hupL) from Pseudomonas hydrogenovora.
AB  - The membrane-bound hydrogenase (Hdg)-encoding structural genes were isolated from
      the hydrogen-utilizing bacterium Pseudomonas hydrogenovora (Ph). Nucleotide
      sequence analysis revealed two genes, hupS and hupL. The hupS gene encoded a 363
      amino-acid (aa) polypeptide (40.4 kDa). The deduced aa sequence contained a
      putative 43-aa leader peptide sequence. The hupL gene started at 55 bp downstream
      from the stop codon of hupS and encoded a 622-aa polypeptide (69.3 kDa). The
      disruption of Ph hupS resulted in the loss of Hdg activity.

PMID- 8529900
TI  - Isolation and characterization of pcp, a gene encoding a pyrrolidone carboxyl
      peptidase in Staphylococcus aureus.
AB  - The pcp gene, encoding a pyrrolidone carboxyl peptidase (PYRase), was cloned from
      a lambda GT11 genomic library prepared from Staphylococcus aureus FDA 574 and
      sequenced. The pcp gene is located 740 bp downstream from cna, a gene that
      encodes a collagen-binding adhesin in S. aureus. S. aureus pcp encodes a 212
      amino-acid (aa) polypeptide. The pcp gene was overexpressed in Escherichia coli
      and the PYRase purified to homogeneity. The recombinant enzyme exhibited
      biological activity, as determined using the chromogenic substrate L-pyroglutamyl
      beta-napthylamide. Biochemical analysis of the PYRase using thiol-blocking
      chemicals suggested that the enzyme belongs to the cysteine peptidase family.
      Moreover, multiple sequence alignment revealed a high degree of similarity to
      previously described bacterial PYRases. This family of peptidases has been used
      to selectively remove the N-terminal pyrrolidone carboxylic acid residue found on
      certain blocked proteins and peptides prior to aa sequencing. However, the exact
      biological role of PYRases has yet to be elucidated.

PMID- 8529901
TI  - Visual evoked potentials after photostress in newly diagnosed insulin-dependent
      diabetes patients.

PMID- 8529902
TI  - Amblyopia in unilateral congenital ptosis: early detection by sweep visual evoked
      potential.

PMID- 8529903
TI  - Comparison of visual field defects between normal-tension and primary open-angle
      glaucoma in the late stage of the disease.

PMID- 8529904
TI  - The retinal depression sign in diabetic retinopathy.

PMID- 8529905
TI  - Sectorization of central 10-deg visual field in open-angle glaucoma. An approach
      for its brief evaluation.

PMID- 8529906
TI  - Formulas for conversion between Octopus and Humphrey threshold values and
      indices.

PMID- 8529907
TI  - DNA-based HLA class II postmortem typing: evaluation of different techniques for
      prospective corneal allografting.

PMID- 8529908
TI  - Indocyanine green angiography in choriocapillary atrophy induced by sodium
      iodate.

PMID- 8529909
TI  - The proportion of trigeminal ganglionic neurons expressing herpes simplex virus
      type 1 latency-associated transcripts correlates to reactivation in the New
      Zealand rabbit ocular model.

PMID- 8529910
TI  - Intraocular irrigating solutions: a comparison of Hartmann's lactated Ringer's
      solution, BSS and BSS Plus.

PMID- 8529911
TI  - Pathway of albumin into the anterior chamber.

PMID- 8529912
TI  - Structure of transient radicals from cytostatic-active p-alkoxyphenols by
      continuous-flow EPR.
AB  - Para-alkoxyphenols are of medical significance as futural cytostatic drugs in
      antimelanoma chemotherapy. They take part in a radical redox-reaction in which
      the catalytically essential protein-linked tyrosyl radical in the functional
      subunit R2 of the growth-regulating enzyme ribonucleotide reductase (RR) is
      quenched. EPR spectroscopy has been employed in conjunction with a continuous
      flow system to study the structure of transient radicals from p-alkoxyphenols
      with different alkyl chain lengths. Radicals of p-alkoxyphenols were generated by
      oxidation in a Fenton system (Ti3+/H2O2,pH1) after rapid mixing in a novel
      continuous-flow EPR cavity designed especially for low consumption of substance.
      Hyperfine structures identified by spectral simulation show that the structure of
      transient radicals from oxidized para-alkoxyphenols (methyl-, ethyl-, allyl
      ,propyl-,iso-propyl-, butyl-, iso-butyl-) belong to the type of phenoxyl radicals
      formed after abstraction of the OH proton. Hyperfine coupling constants are
      similar and vary only slightly with alkyl substituents.

PMID- 8529913
TI  - Inhibition of human low-density lipoprotein oxidation by caffeic acid and other
      hydroxycinnamic acid derivatives.
AB  - The antioxidant activity of the major phenols derived from hydroxycinnamic acid
      (caffeic, ferulic, and p-coumaric acids) on in vitro LDL oxidation was screened,
      using Cu2+ as catalyst. The presence of the second phenolic hydroxy group
      enhanced the inhibitory effect of these compounds. In fact, at 5 microM
      concentration, only caffeic acid completely protected LDL from modification as
      measured as conjugated dienes formation and apo B-100 fragmentation, also
      preserving alpha-tocopherol. The effect of caffeic acid in inhibiting LDL
      oxidative modification induced by three different oxidant systems was tested.
      Using both Cu2+ and 2,2'-azobis (2-amidinopropane)-hydrochloride (AAPH), the
      inhibitory effect of caffeic acid was dose-dependent. Yet, the better protection
      was achieved in the metal-ion dependent system. Also the murine macrophages
      mediated LDL oxidation was efficiently inhibited by 5 microM caffeic acid. UV-VIS
      spectra of caffeic acid incubated with cupric ions show the formation of a
      caffeic acid:copper complex, responsible for a transient chelating activity. This
      mechanism, coupled with its free radical scavenging property, accounts for the
      higher inhibitory activity exhibited by caffeic in Cu(2+)-catalyzed reaction.

PMID- 8529914
TI  - NO2 reactive absorption substrates in rat pulmonary surface lining fluids.
AB  - Inhaled 'NO2 is absorbed by a free radical-dependent reaction mechanism that
      localizes the initial oxidative events to the extracellular space of the
      pulmonary surface lining layer (SLL). Because 'NO2 per se is eliminated upon
      absorption, most likely the SLL-derived reaction products are critical to the
      genesis of 'NO2-induced lung injury. We utilized analysis of the rate of 'NO2
      disappearance from the gas phase to determine the preferential absorption
      substrates within rat SLL. SLL was obtained via bronchoalveolar lavage and was
      used either as the cell-free composite or after constituent manipulation [(i)
      dialysis, treatment with (ii) N-ethylmaleimide, (iii) ascorbate oxidase, (iv)
      uricase, or (v) combined ii + iii]. Specific SLL constituents were studied in
      pure chemical systems. Exposures were conducted under conditions where 'NO2 is
      the limiting reagent and disappears with first-order kinetics ([NO2]0 < or = 10
      ppm). Reduced glutathione and ascorbate were the principle rat SLL absorption
      substrates. Nonsulfhydryl amino acids and dipalmitoyl phosphatidylcholine
      exhibited negligible absorption activity. Whereas uric acid and vitamins A and E
      displayed rapid absorption kinetics, their low SLL concentrations preclude
      appreciable direct interaction. Unsaturated fatty acids may account for < or =
      20% of absorption. The results suggest that water soluble, low molecular weight
      antioxidants are the preferential substrates driving 'NO2 absorption.
      Consequently, their free radicals, produced as a consequence of 'NO2 exposure,
      may participate in initiating the 'NO2-induced cascade, which results in
      epithelial injury.

PMID- 8529915
TI  - Cellular injury induced by oxidative stress is mediated through lysosomal damage.
AB  - Cultured primary hepatocytes pretreated (protected) with the iron chelator
      deferoxamine or the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD) were
      resistant to the toxicity of 5 microM naphthazarin (5,8-dihydroxy-1,4
      naphthoquinone) during a 180-min exposure. Hepatocytes exposed to naphthazarin
      without any protection were abruptly depleted of intracellular reduced
      glutathione, and the level of cytosolic Ca2+ was rapidly increased. This was
      followed by lipid peroxidation, measured as accumulation of malondialdehyde (MDA)
      and 4-hydroxyalkenals (4-HNA) intra- and extracellularly; decrease in ATP levels;
      destabilization of lysosomes; and finally cell death. The stability of the
      lysosomal membranes was evaluated by determining retention of the lysosomotropic
      weak base acridine orange (AO). Naphthazarin exposure caused leakage of protons
      from the acidic compartment, as indicated by relocalization of AO to the cytosol.
      Protection of the cell cultures with deferoxamine or DPPD prevented
      destabilization of lysosomes and cell killing. It also reduced the loss of ATP
      but did not prevent the depletion of glutathione or the increase in Ca2+. In
      cells subjected to naphthazarin exposure, DPPD protection also completely
      inhibited lipid peroxidation, whereas deferoxamine pretreatment only slightly
      reduced the intracellular accumulation of MDA and 4-HNA but completely prevented
      cell rupture and the leakage of these lipid peroxidation products to the medium
      that took place in large amounts from unprotected cells exposed to naphthazarin.
      Deferoxamine is taken up by endocytosis and is thus transported to the acidic
      vacuolar apparatus, whereas the lipophilic DPPD is rapidly distributed throughout
      the cells. Inhibiting endocytosis during deferoxamine pretreatment, by incubating
      at +4 degrees C or by preexposure to a mixture of the endocytosis-inhibitors
      cytochalasin B and monensin, abolished the protective effect of deferoxamine. The
      findings suggest that naphthazarin-induced cell killing is not caused directly by
      either thiol oxidation or an increase in cytosolic free Ca2+, but rather is
      preceded by lysosomal destabilization, which may be prevented either by
      inhibition of cellular peroxidation in general or by prevention of iron-catalyzed
      oxidative reactions, and involves peroxidation of cellular membranes, energy
      depletion, and leakage of lysosomal content. DPPD would protect against cell
      killing by preventing lipid peroxidation of cellular membranes in general,
      whereas deferoxamine seems to allow a limited general cellular peroxidation but
      specifically prevents peroxidation and fragmentation of lysosomal membranes by
      chelating intralysosomal iron and, consequently, leakage of destructive lysosomal
      contents with ensuing cell rupture and death. Thus, a certain degree of cellular
      peroxidation does not appear to be lethal as long as lysosomal membranes are
      protected, placing lysosomes into a category of cellular loci minora resistentia.

PMID- 8529916
TI  - Beta-carotene as an interceptor of free radicals.
AB  - Kinetics of nonenzymic and nonphotochemical oxidation of beta-carotene have been
      studied. The rate constants for the reactions of beta-carotene with initiator
      derived C-centered and peroxyl radicals in solution were measured as
      approximately 10(4) and 5 x 10(5) - 1 x 10(4) M-1s-1, respectively. beta-Carotene
      derived free radicals have been shown to be less reactive toward polyene than
      initiator-derived radicals. This suggests that beta-carotene might behave as an
      interceptor of free radical species regardless of the oxygen pressure in the
      environment. The mechanism for beta-carotene oxidation covering the main pathways
      for formation, transformation, and decay of free radicals has been formulated. In
      combination with experimental kinetic parameters and their temperature
      correlation, computer modeling has been used to solve the reaction kinetics
      numerically. The model proposed enables analysis of the kinetics of beta-carotene
      consumption and oxygen uptake under various conditions, as well as the influence
      of beta-carotene on oxidation of polyunsaturated fatty acids and their esters.

PMID- 8529917
TI  - Inhibition of adenine nucleotide translocator by lipid peroxidation products.
AB  - Our previous data showed that aldehydic lipid peroxidation products, interacting
      with mitochondrial membrane lipids, could alter the physicochemical status of the
      membrane. This study was initiated to examine the interaction of these aldehydes
      with a major mitochondrial protein, the adenine nucleotide translocator (ANT).
      Our findings showed that the transporting activity of ANT in intact mitochondria
      was inhibited by two unsaturated aldehydes, 4-hydroxynonenal (HNE) and 4
      hydroxyhexenal (HHE). To probe further into the underlying mechanism of this
      inhibition, a reconstituted ANT model was developed by incorporating isolated ANT
      into liposomes. Pretreatment of ANT with HNE prior to reconstitution resulted in
      decreased activity in the reconstituted ANT. Further investigation revealed that
      this decreased activity was probably due to loss of sulfhydryl groups, which are
      essential for ANT activity. Interestingly, pretreatment of the liposomes with HNE
      also caused a decrease in the reconstituted ANT activity by indirectly altering
      the physiochemical status of the lipid environment in which ANT was embedded.
      These results demonstrate that the reactive aldehydes derived from mitochondrial
      lipid peroxidation can impair the membrane function by interacting with both the
      protein and the lipid moieties in the membrane. Thus, the varied damaging effects
      associated with lipid peroxidation may be mediated by their secondary aldehydic
      byproducts.

PMID- 8529918
TI  - Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester,
      and succinate ester forms of vitamin E.
AB  - The bioavailability of RRR-alpha-tocopherol from the oral administration of RRR
      alpha-tocopherol itself and its acetate and succinate esters was determined in
      healthy human subjects. Venous blood samples were withdrawn periodically over a
      51-h period following oral administration of a gelatin capsule containing an
      equimolar mixture of RRR-alpha-tocopherol and RRR-alpha-tocopheryl acetate. In a
      second study, subjects received a capsule containing an equimolar mixture of RRR
      alpha-tocopheryl acetate and RRR-alpha-tocopheryl succinate. In Study 1, RRR
      alpha-tocopherol was absorbed at similar rates from both the free phenol, and the
      acetate ester and maximum plasma levels occurred at 12 h in most subjects. The
      extent of absorption of RRR-alpha-tocopherol varied considerably between subjects
      in absolute terms, but the relative absorption from the two forms was remarkably
      consistent, and a ratio of 1.0 was found for parameters of relative
      bioavailability in plasma. The concentration of RRR-alpha-tocopherol from each
      form was maximal at approximately 27 h in red blood cells and, as seen with the
      plasma data, there was a large interindividual variability. In Study 2, there was
      no significant difference in the extent of absorption of RRR-alpha-tocopherol
      from the acetate ester and the succinate ester, although there was an apparently
      higher initial rate of absorption from the acetate ester.

PMID- 8529919
TI  - Oxidizability and subsequent cytotoxicity of chylomicrons to monocytic U937 and
      endothelial cells are dependent on dietary fatty acid composition.
AB  - Oxidized chylomicrons may be a metabolic factor involved in the injury of the
      arterial wall and may constitute a potential link between postprandial lipemia
      and atherogenesis. It was of interest to study the influence of dietary fatty
      acid composition on the oxidizability and subsequent cytotoxicity of chylomicrons
      on cultured cells. Human chylomicrons were obtained from healthy volunteers 3 h
      after ingestion of a triglyceride-rich meal containing mainly either
      polyunsaturated fatty acids (soya oil) or monounsaturated fatty acids (olive oil)
      or saturated fatty acids (partly hydrogenated palm oil). Polyunsaturated fatty
      acid (PUFA)-rich chylomicrons exhibited a high oxidizability, whereas
      chylomicrons enriched with monounsaturated or saturated fatty acids were
      relatively resistant to oxidation. The cytotoxicity of various types of
      chylomicrons submitted to oxidation has been tested comparatively on cultured
      human monocytic U937 cells and endothelial cells. Chylomicrons enriched with
      saturated and monounsaturated fatty acids were not or only slightly cytotoxic to
      cultured cells, whereas PUFA-rich chylomicrons (highly susceptible to oxidation)
      were highly cytotoxic. The influence of cholesterol on the oxidizability and
      subsequent cytotoxicity of PUFA-rich chylomicrons has been investigated by using
      comparatively a soya diet supplemented or not with cholesterol. PUFA-rich
      cholesterol-rich chylomicrons were slightly more oxidizable and more cytotoxic
      than PUFA-rich (cholesterol-poor) chylomicrons, thus suggesting that the
      cytotoxicity of PUFA-rich chylomicrons may be due to oxidation derivatives of
      PUFA (for the major part) and to oxysterols (for a minor part). Furthermore, the
      cytotoxic effects of oxidized PUFA-rich chylomicrons and of mildly oxidized LDL
      were in similar range (even higher for PUFA-rich chylomicrons when expressed per
      lipoprotein particle), thus suggesting that oxidized PUFA-rich chylomicrons may
      play a nonnegligible role in cytotoxic events occurring during
      atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529920
TI  - Effect of lipid ozonation products on liposomal membranes detected by Laurdan
      fluorescence.
AB  - We report here the influence of the lipid ozonation products, 1-palmitoyl-2-(9
      oxononanoyl)-sn-glycero-3-phosphocholine (PC-aldehyde) and 1-palmitoyl-2[8-(5
      octyl-1, 2, 4,-trioxolan-3-yl)- octanoyl]-sn-glycero-3-phosphocholine (PC-Criegee
      ozonide), on the phase domains of small unilamellar vesicles. (See Scheme 1 for
      structures.) 6-Lauroyl-2-dimethylaminonaphtalene (Laurdan) fluorescence
      excitation and emission spectra and generalized polarization measurements allowed
      us to study how lipid ozonation products affect the phase components of
      phospholipid membranes. A shift of excitation and emission spectra and a decrease
      in generalized polarization reveal the presence of a more polar environment
      surrounding the probe. We find that when either PC-aldehyde or PC-Criegee ozonide
      are incorporated into a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      membrane, or when the POPC membrane is directly ozonated, a change in polarity of
      the phospholipid environment occurs that changes the properties of the bilayer.
      The introduction of more oxygenated and more polar phospholipids creates a more
      polar environment allowing the deeper penetration of water molecules into the
      membrane. Water penetration also is facilitated by the membrane disorder
      producing effect of the ozonation products. The presence of an increased number
      of water molecules in the membrane effects the bilayer, altering packing order
      and cooperatively among fatty acyl chains as well as enhancing membrane fluidity.

PMID- 8529921
TI  - Comparison of the effects of dietary vitamin E on in vivo and in vitro parameters
      of lipid peroxidation in the rabbit.
AB  - This study has investigated the effect of dietary vitamin E on markers of
      antioxidant status. Four groups of rabbits received diets containing 30 energy
      percent (en%) total fat (7.8 en% contributed by linoleic acid) for 12 weeks. D,1
      alpha tocopheryl acetate was added to the diets to obtain a range of vitamin E
      concentrations (49, 114, 179, or 775 tocopherol equivalents per kg diet).
      Increased vitamin E concentrations were demonstrated in plasma lipoproteins and
      erythrocyte membranes following supplementation, and dietary effects on lipid
      peroxidation were investigated by (i) monitoring a fluorescent parinaric acid
      probe incorporated into erythrocyte membranes in vivo, (ii) determination of
      malondialdehyde and oxysterols in plasma, and (iii) investigation of the
      susceptibility of low density lipoprotein (LDL) to copper-induced conjugated
      diene formation in vitro. No effects of vitamin E were observed on parinaric acid
      oxidation in vivo or on the accumulation of lipid peroxidation products in
      plasma, but the resistance of LDL to oxidation in vitro increased significantly
      as vitamin E was supplemented to the diets. Our results demonstrate that under
      these dietary conditions (7.8 en% linoleic acid) increasing the vitamin E content
      of plasma and erythrocytes approximately two-fold does not reduce the level of
      lipid peroxidation in vivo, indicating sufficient antioxidant capacity on the
      lowest vitamin E diet. In contrast, LDL became more resistant to an extreme
      oxidative stress applied in vitro. The relevance of these assays to currently
      proposed mechanisms of atherosclerosis is discussed.

PMID- 8529922
TI  - Effects of N-acetylcysteine in the rat heart reperfused after low-flow ischemia:
      evidence for a direct scavenging of hydroxyl radicals and a nitric oxide
      dependent increase in coronary flow.
AB  - The capacity of N-acetylcysteine to directly scavenge hydroxyl radical produced
      by rat hearts reperfused after 90 min of low-flow ischemia was assessed by the
      hydroxylation of 4-hydroxybenzoate into 3,4-dihydroxybenzoate using a gas
      chromatography-mass spectrometric assay. Reperfused hearts showed a massive
      release of 3,4-dihydroxybenzoate, lactate dehydrogenase, and total glutathione,
      contained less reduced and oxidized glutathione, but maintained spontaneous
      beating and coronary flow rates close to preischemic values. Compared to
      untreated hearts: reperfused hearts treated with N-acetylcysteine from the start
      of ischemia (i) released four times less 3,4-dihydroxybenzoate, but similar
      amounts of lactate dehydrogenase or glutathione, (ii) showed a nitric oxide
      dependent increase in coronary flow rate, and (iii) contained less oxidized
      glutathione, but similar amounts of reduced glutathione. Reperfused hearts
      receiving N-acetylcysteine since the last 5 min of ischemia had also a four-times
      lower 3,4-dihydroxybenzoate release, but their coronary flow rate response was
      similar to that of untreated hearts. These results indicate that N-acetylcysteine
      can directly scavenge hydroxyl radicals produced by reperfused ischemic hearts,
      although this effect is not associated with any protective effects as indicated
      by the lactate dehydrogenase and glutathione release and cannot explain the
      nitric oxide-dependent reperfusion hyperemia.

PMID- 8529923
TI  - DNA oxidation as a potential molecular mechanism mediating drug-induced birth
      defects: phenytoin and structurally related teratogens initiate the formation of
      8-hydroxy-2'-deoxyguanosine in vitro and in vivo in murine maternal hepatic and
      embryonic tissues.
AB  - A considerable number of teratogens, including the anticonvulsant drug phenytoin
      and structurally related drugs and environmental chemicals, may be bioactivated
      by peroxidases, such as prostaglandin H synthase (PHS) and lipoxygenases (LPOs),
      to a reactive free radical intermediate that initiates birth defects. However,
      the molecular targets of the reactive free radical intermediates mediating
      chemical teratogenesis, and hence the fundamental determinants of susceptibility,
      are poorly understood. In these studies, a teratogenic dose of phenytoin (65
      mg/kg), when injected into pregnant CD-1 mice during organogenesis on gestational
      day 12, initiated the oxidation of DNA in maternal hepatic and embryonic nuclei,
      forming 8-hydroxy-2'-deoxyguanosine. Significant maternal and embryonic DNA
      oxidation occurred at 6 and 3 h, respectively, suggesting relative embryonic
      deficiencies in free radical-related cytoprotective enzymes, although the rates
      appeared similar. Maximal DNA oxidation in both maternal and embryonic tissues
      occurred at 6 h, presumably reflecting the balance of DNA oxidation and repair,
      the latter of which appeared similar in both tissues. Inhibition of phenytoin
      initiated embryonic DNA oxidation by the free radical spin trapping agent alpha
      phenyl-N-t-butylnitrone (41.5 mg/kg), and by acetylsalicylic acid (10 mg/kg), an
      inhibitor of the cyclooxygenase component of PHS, was consistent with the
      previously reported reduction by these inhibitors of phenytoin-initiated murine
      birth defects. In vitro studies using a horseradish peroxidase (0.5 mg/ml)-H2O2
      (5.45 micrograms/ml) bioactivating system for drug-initiated oxidation of 2'
      deoxyguanosine (3.74 mM), indicated that the potency of xenobiotic-initiated
      formation of 8-hydroxy-2'-deoxyguanosine for the structurally related drugs and
      metabolites phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, trimethadione,
      dimethadione, l-mephenytoin, l-nirvanol, d-nirvanol (80 microM each), or
      thalidomide (64 microM), reflected their murine teratogenic potency. Given the
      relatively low activities of cytochromes P450, compared to PHS and LPOs, in human
      and rodent embryonic tissues, these data support the potential teratological
      importance of peroxidase-catalysed bioactivation of xenobiotics with structural
      similarities to phenytoin. These studies provide the first evidence that
      peroxidase-catalysed embryonic DNA oxidation may constitute a critical molecular
      mechanism mediating the teratogenicity of phenytoin and related drugs and
      environmental chemicals, and suggest the potential teratological importance of
      additional embryonic processes, such as DNA repair and tumor suppressor genes, as
      determinants of susceptibility.

PMID- 8529924
TI  - Oxidant stress and endothelial membrane transport.
AB  - The endothelium modulates vascular tone, vasoreactivity, and permeability in
      response to agonist-stimulation. Much of the pathophysiology of oxidant-induced
      vascular injury can be attributed to endothelial cell dysfunction. In the past
      several years, the effects of oxidant stress on agonist-stimulated Ca(2+)
      channels have been described. More recently, the effects of oxidant stress on
      several other endothelial membrane-transport systems have been elucidated. It now
      appears that inhibition of the agonist-stimulated Ca2+ channel is due at least in
      part to membrane depolarization via oxidant-activation of a Na(+)-permeable,
      nonselective cation channel. In this review, the effects of oxidant stress on ion
      transport through the agonist-stimulated Ca2+ influx channel, Na+ and K+
      channels, Na+/K(+)-ATPase, Ca(2+)-ATPase, and the Na+/K+/2Cl- cotransporter are
      discussed. The interrelated effects of oxidant stress on these endothelial
      membrane transport pathways are considered, and the net effect on Ca2+ signaling
      is described.

PMID- 8529925
TI  - Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice.
AB  - A single intravenous injection of doxorubicin (DOX, 30 mg/kg body weight) caused
      a significant rise in the content of lipid peroxidation products in hearts of
      mice. The concentration of conjugated dienes (CD) and malondialdehyde (MDA) found
      24 h after injection of DOX increased about 1.8- and 2.4-fold and reached values
      of 11.31 +/- 2.24 A233/g and 3.72 +/- 0.40 mumol/g, respectively. The same dose
      of 4'-epi-doxorubicin (EPI), a less cardiotoxic epimer of DOX, increased only the
      heart level of MDA. Both antracyclines were not able to induce increased
      formation of CD in murine liver and lungs. Ambroxol, an expectorant drug which
      possesses the ability to scavenge hydroxyl radicals, injected intravenously (70
      mg/kg) 30 min prior to DOX, completely abolished the rise in heart content of CD
      and MDA. The heart levels of CD and MDA in animals treated with ambroxol and DOX
      were 3 and 2.7 times lower than those observed in mice treated with water and
      DOX, respectively. Ambroxol had no effect on DOX- and EPI-induced formation of
      MDA in the lungs. Our results indicate that (1) DOX is a more powerful inductor
      lipid peroxidation in the heart than EPI; and (2) ambroxol may be useful in
      preventing lipid peroxidation in the heart caused by DOX.

PMID- 8529927
TI  - PHGPx and phospholipase A2/GPx: comparative importance on the reduction of
      hydroperoxides in rat liver mitochondria.
AB  - The comparative importance of phospholipid hydroperoxide glutathione peroxidase
      (PHGPx) and of "classic" glutathione peroxidase (GPx) in the reduction of
      phospholipid hydroperoxides is unclear. Although GPx activity is 500-fold higher
      than that of PHGPx in rat liver, the reduction of phospholipid hydroperoxides by
      glutathione (GSH) through GPx may be strongly limited by a low PLA2 activity. We
      address this issue using a moderately detailed kinetic model of mitochondrial
      lipid peroxidation in rat liver. The model was based on published data and was
      subjected to validation as reported in the references. It is analysed by computer
      simulation and sensitivity analysis. Results suggest that in rat liver
      mitochondria PHGPx is responsible for almost all phospholipid hydroperoxide
      reduction. Under physiological conditions, the estimated flux of phospholipid
      hydroperoxides reduction through PHGPx is about four orders of magnitude higher
      than the estimated hydrolysis flux through PLA2. On the other hand, virtually all
      hydrogen peroxide is reduced through GPx. Therefore, a functional complementarity
      between PHGPx and GPx is suggested. Because the results are qualitatively robust
      to changes of several orders of magnitude in PLA2 and PHGPx levels, the
      conclusions may not be limited to mitochondria.

PMID- 8529926
TI  - Phenytoin-induced glutathione depletion in rat peripheral nerve.
AB  - Administration of high doses (150-250 mg/kg body weight) of phenytoin (DPH)
      promote a 40% decrease in glutathione (GSH) content of rat sciatic nerve. This
      DPH-induced GSH depletion is accompanied with an electrophysiological impairment
      of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior
      to DPH), a protein kinase C inhibitor, was able to prevent the DPH-induced GSH
      depletion only at the lower DPH dose used. This same inhibitor completely
      prevented the electrophysiological impairment at the lower DPH dose, and only
      partially at the higher DPH dose used. These results confirm the hypothesis of a
      DPH-dependent activation of PKC (that might be triggered by, or be the
      consequence of, the reduction of the intracellular antioxidant GSH), as one of
      the pathophysiological mechanisms involved in DPH-induced neurotoxicity.

PMID- 8529928
TI  - Breath pentane and plasma lipid peroxides in ischemic heart disease.
AB  - This study examined the relationship between breath pentane and plasma lipid
      peroxide levels sampled simultaneously in patients with stable angina (n = 17),
      unstable angina (n = 23), and controls (n = 10). Plasma lipid peroxides were
      measured in venous blood as the adduct formed between thiobarbituric acid and
      malondialdehyde (MDA) using high performance liquid chromatography. Pentane was
      measured in end-expiratory air using gas chromatography. MDA concentrations in
      stable (1.81 +/- 0.84 mumol/l) and unstable (1.5 +/- 1.23 mumol/l) angina were
      not different. However, both groups had significantly (p < 0.005) elevated MDA
      levels compared to controls (0.41 +/- 0.26 mumol/l). Breath pentane was 0.20 +/-
      0.12 nmol/l in controls and not different from stable angina (0.26 +/- 0.20
      nmol/l) or unstable angina (0.15 +/- 0.07 nmol/l). When the data from all three
      groups were combined, there was no correlation between pentane and MDA (rho = 
      0.09, p = 0.54). In five of the unstable angina patients treated with balloon
      angioplasty, MDA in pulmonary arterial blood rose by 69 +/- 15% (p < 0.01), and
      breath pentane rose by 73 +/- 20% (p < 0.01) immediately after balloon deflation.
      One minute after balloon deflation MDA and pentane had returned to preinflation
      levels. The results suggest that basal levels of pentane are less useful than MDA
      as an index of lipid peroxidation in patients with coronary artery disease.
      However, breath pentane appears to be a sensitive index of reperfusion-induced
      lipid peroxidation.

PMID- 8529929
TI  - 4-hydroxynonenal is degraded to mercapturic acid conjugate in rat kidney.
AB  - The cytotoxic lipid peroxidation product 4-hydroxynonenal (HNE) was infused into
      rat kidney. During the first 2 min a rapid degradation of a 100 microM HNE
      solution was demonstrated. After 5 min the consumption rate of 4-HNE reached a
      steady state of about 75 nmoles/ml. The total HNE consumption rate was about 200
      nmoles/g w.w./min. The excretion rate into urine was about 0.1% of total HNE
      consumption. It could be demonstrated that the HNE-mercapturic acid formation
      takes place in the kidney. The formation of the HNE-mercapturic acid contributes
      up to 6% to total HNE consumption. Within 10 min of perfusion 2% of the HNE
      mercapturic acid were excreted into urine. The residual 98% flow back into the
      blood circulation.

PMID- 8529930
TI  - Lead amplifies glutamate-induced oxidative stress.
AB  - Lead markedly amplified L-glutamate-induced oxidative stress, that is, increased
      L-glutamate-induced production of reactive oxygen species, decreased cellular
      glutathione, and induced cytotoxicity in human neuroblastoma cells. It was
      notable that oxidative burst induced by L-glutamate alone was observed only when
      neuronal glutathione was depleted. A role of protein kinase C (PKC) in glutamate
      induced production of reactive oxygen species is likely because it was blocked by
      a PKC inhibitor. We suggest here that the mechanism whereby lead causes its
      neurotoxicity may be through the amplification of glutamate-induced oxidative
      stress, possibly through PKC activation.

PMID- 8529931
TI  - Nitration of tyrosyl-residues from extra- and intracellular proteins in human
      whole blood.
AB  - We measured the amounts of tyrosine and 3-nitrotyrosine (NO2-tyrosine) in
      proteins of plasma and polymorphonuclear leukocytes (PMN) from human whole blood
      before and after activation with phorbol ester (PMA) or calcium ionophore (A
      23187). In unstimulated blood, no significant nitration of tyrosine was detected
      into PMN proteins, but a NO2-tyrosine/tyrosine ratio of 0.7% was detected in
      plasma proteins. When blood was activated with PMA, the NO2-tyrosine/tyrosine
      ratio stayed at 0.7% in plasma proteins, but it increased to 1.4% in PMN
      proteins, indicating a peroxynitrite production within the cells. In blood
      activated with calcium ionophore, the NO2-tyrosine/tyrosine ratio was 1.2% in
      plasma proteins and 2.1% in PMN proteins. Incubation of blood with a NO-synthase
      inhibitor before stimulation inhibited such a protein tyrosine nitration. To
      ensure that NO2-tyrosine detected in intracellular proteins did not result from
      the enzymatic posttranslational tyrosylation of PMN proteins, the incorporation
      of 14C labeled tyrosine into PMN proteins after activation with PMA or A23187 was
      studied. The addition of a 10 fold excess of NO2-tyrosine did not modify the
      course of protein tyrosylation. Because tyrosine nitration is an irreversible
      reaction, NO2-tyrosine could be accumulated into proteins and could act as a
      cumulative index of peroxynitrite production.

PMID- 8529932
TI  - Inhibition of hydroxyl radical production by lactobionate, adenine, and tempol.
AB  - Superoxide and hydroxyl free radicals are strongly implicated in the deleterious
      effects of reperfusion of grafted organs. Iron ions are critical in the Fenton
      like reaction that generates oxygen-free radicals from H2O2. Using the
      ADP/Fe2+/H2O2 .OH-generating system, we demonstrated that components of an organ
      preservation solution (Henri Mondor solution): sodium lactobionate, adenine, and
      a nitroxide radical: 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL),
      showed unexpected inhibition properties on the production of hydroxyl radicals by
      complexation of Fe2+ for lactobionate and nitroxide or Fe3+ for adenine. This
      inhibition was 75.5% at 12 mM lactobionate. Moreover, a complete inhibition was
      observed at 50 mM. At 0.25 mM adenine, the reduction was 14.8% (maximum effect:
      34.1%). Henri Mondor solution, at an identical adenine and lactobionate
      concentration, inhibited the radical production by 91.5%, indicating an additive
      effect. Nitroxide totally inhibited .OH production by the ADP/Fe2+/H2O2 system
      (maximum effect: 95.6%) and partially the production by an O2.- generating system
      (maximum effect: 74.8%). Thus, the association of these three components in
      preservation solutions would be an original method to limit the reperfusion
      injury observed in isolated ischemic organs.

PMID- 8529933
TI  - [Natural cytotoxicity of CD16+ lymphocytes in women with selected states of
      pregnancy pathology].
AB  - The natural cytotoxic activity of lymphocytes CD16+ (NK) was studied in healthy
      nonpregnant and pregnant women and in patients with threatened spontaneous
      abortion, preterm delivery and preeclampsia. We have shown no differences in the
      proportion of NK cells between all studied patients and controls. The possibility
      of previous contact with embryonic antigens was excluded since no differences
      were noted between cytotoxic activity of NK cells obtained from multiparous women
      and those who never gave a birth. The natural cytotoxic activity of NK cells from
      patients with threatened abortion or preterm delivery was found to be
      significantly higher (p < 0.01) than from cells of healthy pregnant women.
      However in preeclamptic patients activity of NK cells was very low as comparing
      to pregnant women and more than three lower than in nonpregnant ones. This
      indicates that though the amount of NK cells does not different between normal
      and pathological pregnancies, there is marked difference in their biological
      activity.

PMID- 8529934
TI  - [Analysis of mean differences for acid-base balance parameters in blood from
      umbilical arteries and veins of newborns with perinatal hypoxemia].
AB  - Arterio-venous differences in acid-base parameters of umbilical vessels blood
      using Nickelsen and Weber method and SPSS/PC+ computer's program were calculated.
      The mean differences are dependent on fetal metabolism, umbilical blood flow and
      placental gas exchange. Arterio-venous differences--normal or increased for pH,
      PCO2, PO2 and SO2 are valuable diagnostic indicators of accurate gas exchange
      while decreased values of these differences should predict placental dysfunction.
      Small differences are signs of chronic fetus hypoxaemia originated by anaerobic
      metabolism and increased the fetal lactic acid production, respectively.

PMID- 8529935
TI  - [Association between magnesium, calcium, phosphorous, copper and zinc in plasma
      and erythrocytes of umbilical cord blood and biometric parameters of newborns].
AB  - The correlation between magnesium, calcium, phosphorous, copper, and zinc in
      umbilical cord plasma and erythrocytes and gestational age, birth height, weight
      and head circumference were calculated in 52 newborn infants (27 girls, and 25
      boys). No infant had a congenital malformation, all pregnancies were
      uncomplicated, mothers were healthy and had no history of serious diseases. There
      were no significant sex-related differences at birth among the variables studied.
      Gestational age was positively correlated with erythrocyte zinc. Birthweight
      positively correlated with erythrocyte magnesium and zinc. Height of neonate
      positively correlated with calcium in plasma. Plasma calcium was positively
      correlated with erythrocyte copper. The most significant regressors accounting
      for birthweight were erythrocyte zinc followed by plasma zinc. Reference values
      in umbilical cord plasma and erythrocytes for magnesium, calcium, phosphorous,
      copper and zinc was also determined.

PMID- 8529936
TI  - [Analysis of seven year prophylactic examinations of uterine cervix carcinoma in
      women living in the town of Kielce].
AB  - The authors are presenting an analysis of the prophylactic examinations carried
      out within the period of seven years among women under the care of the Municipal
      Health Care Center in Kielce. They are also trying to evaluate the influence such
      examinations have in forming up the detectability of preneoplastic states and
      cancer of the uterine cervix. The studies were carried out from 1982-1988. A rule
      was adopted to repeat the examinations every two years. Owing to organizing
      difficulties, the first stage of the examinations took three years. The basis of
      the prophylactic examinations was cytologic examination. The detectability of
      intraepithelial neoplasm of the uterine cervix (CIN) in the three stages was
      0.26%, 0.16%, and 0.07%. It was observed therefore, the gradual drop in the
      number of the detectable CIN among the population in the duration of the studies.
      A "shift" of detectable neoplasma changes in the uterine cervix in the direction
      of a higher percentage of preinvasive cancers and with an early invasion was
      observed. This shift, beside the stable decrement of the absolute number of
      detectable cancers is a favourable phenomenon and testifies the great usefulness
      and the effectiveness of the studies.

PMID- 8529937
TI  - [The quality of life in particular phases of disease in women treated for genital
      neoplasms].
AB  - The authors have performed psychological analysis in women with diagnosed
      neoplasma of the genital organs. All of them were treated with radiotherapy. The
      quality of life depended on the phase of the disease in which they had been.

PMID- 8529938
TI  - [Homogeneous dysgerminoma of the ovary. Analysis of 25 cases].
AB  - Between 1972 and 1985, 25 patients with ovarian pure dysgerminoma were treated in
      the Center of Oncology in Cracow. In twenty-two (88%) patients total abdominal
      hysterectomy with bilateral salpingo-oophorectomy and postoperative radiotherapy
      was undertaken. Unilateral salpingo-oophorectomy alone was undertaken in 3
      patients in stage IA. The five-year disease-free survival for all patients was
      84%, for patients in stage IA degrees -- 100% (11/11), I degree -- 94.4% (17/18),
      II degrees and III degrees -- 57.1% (4/7).

PMID- 8529939
TI  - [Excretion of free catecholamines in urine and water electrolyte balance in women
      with arterial hypertension during, before and after menopause].
AB  - This study was performed in 120 women, divided into two groups: premenopausal and
      early postmenopausal. The average age in the premenopausal group was 49.92 and in
      the postmenopausal group was 52.8 years. Each group was subdivided according to
      arterial pressure with normal pressure and arterial hypertension. Daily urinary
      excretion of catecholamines was determined to method of Euler and Lishajko. The
      concentration of sodium, potassium and calcium ions was determined using method
      of colorimetric by means of RA-1000 apparatus of Technicon make. The chloride
      concentration was determined using method of coulometric by means of CMT-10
      apparatus of Radiometer make. It was found that women with menopausal arterial
      hypertension have significantly greater urinary excretion of adrenaline and have
      noradrenaline (p < 0.001) in the premenopausal period, and adrenaline (p < 0.01)
      in the postmenopausal period. Also for women with the menopausal arterial
      hypertension the concentration of sodium and potassium ions was significantly
      greater in serum, and no changes in urinary.

PMID- 8529940
TI  - [Postcoital test evaluated in peritoneal fluid].
AB  - The role of the peritoneal fluid in the physiology of reproduction, as well as in
      the transportation and survival of gametes, is little recognized. Taking this
      into consideration, the authors have examined the occurrence of spermatozoa in
      the peritoneal fluid, collected from patients during diagnostic laparoscopies,
      following intrauterine insemination with husband's sperm, in, so-called,
      Templeton's Test. In the group of patients with cervical factor six (6) mobile
      spermatozoa (85%) were observed, in the group with male factor -- three (3) (42%)
      and in the group with idiopathic infertility -- 1 (25%). A high utility of this
      test has been indicated, especially in infertility caused by the male factor and
      in endometriosis.

PMID- 8529941
TI  - [Immunohistochemical localization of estrogen receptors in vesicovaginal fascia
      among female patients with stress incontinence--preliminary report].
AB  - Using monoclonal antibody assay technique 29 kD domain of estrogen receptor was
      found and partially quantitated by means of histological score in fibroblasts
      from vesico-vaginal fascia obtained during surgical procedure in incontinent
      women. This is an important proof that estrogen supplementation therapy is a
      reasonable approach in women affected by urinary stress incontinence.

PMID- 8529942
TI  - [Multicenter study of Klimonorm (R) by the Jenapharm firm for treating the
      climacteric syndrome].
AB  - In our work we evaluated according to Kupperman Index the effectiveness of
      treating menopausal signs and symptoms during the therapy with estrogen-
      progestagen preparation Klimonorm firm Jenapharm. During 6 months observation
      increase in blood pressure was not observed, neither an increase in body weight
      in a group of 116 women was not observed. Among these, mean Kupperman index was
      decreased from 28.38 to 11.6 after 3 months and up to 5.47 after 6 months therapy
      with Klimonorm. These patients estimated this agent as very good and good in
      93.21% tolerated as very good and good in 91.43% and 91.59% of these patients
      planned to continue treatment with Klimonorm.

PMID- 8529943
TI  - [Non-Hodgkin's lymphoma of the uterine cervix].

PMID- 8529944
TI  - [An enormous oviduct hematoma coexisting with a residual uterus horn in an
      adolescent].
AB  - The case of tremendous salpinx hematoma coexisting with a residual uterus horn
      has been described. A menstrual blood from the little cavity of residual horn
      filled progressively the salpinx, which had abdominal ostium closed. A congenital
      malformation, in consequence of Muller tubes defective development, has been a
      direct cause of the disease. The ethology of the malformation has not been found.
      Primary diagnosis suggested an ovarian cyst or a malignant tumour. Neither
      physical examination nor USG made the diagnosis easier. The case has showed, how
      difficult the recognition of pelvic tumours in young women is. Sonography may be
      very helpful in diagnosing of such malformations but in early stages only.

PMID- 8529945
TI  - Serum levels of androgens and estrogens and 'steroid-sensitive' liver proteins in
      early human pregnancy: influence on the gender of the offspring.
AB  - Serum androgens, estrogens, 'steroid-sensitive proteins', thyroid components, and
      albumin were measured twice within a 4-5 week interval in 44 cases of early
      normal pregnancy (gestational weeks 8-18). Positive correlations were found in
      the total material between dehydroepiandrosterone sulfate (DHAS) and testosterone
      (T), unconjugated and total estrone, albumin, tetraiodothyronine, and calculated
      free tetraiodothyronine concentrations and within 2-week intervals between DHAS
      and T, estradiol-17 beta, and unconjugated and total estrone, and between T and
      estradiol-17 beta and unconjugated estrone. Positive correlations were also found
      between the rates of change in DHAS of albumin. No significant association was
      found between 'steroid-sensitive proteins' and androgens or androgen/estrogen
      ratios. Women giving birth to girls had significantly higher serum levels of
      pregnancy-associated alpha 2-macroglobulin, thyroxine-binding globulin, and
      ceruloplasmin and lower ratios between T and sex hormone binding globulin than
      women giving birth to boys. The important role of placental aromatization in the
      metabolism of maternal androgens is well known. Albumin binding and thyroid
      status may also affect the metabolism of DHAS during pregnancy. The
      androgen/estrogen balance may be of little importance for the regulation of
      'steroid-sensitive' proteins during early pregnancy. The mechanism behind the
      higher serum levels of pregnancy-associated alpha 2-macroglobulin, thyroxine
      binding globulin, and ceruloplasmin in women giving birth to girls remains to be
      elucidated.

PMID- 8529946
TI  - Evaluation of a new embryo-grading system to predict pregnancy rates following in
      vitro fertilization.
AB  - This study examines two descriptive parameters of embryo morphology to determine
      if either parameter correlates with subsequent pregnancy rates (PRs). The two
      parameters were the evenness (similarity in size) of the blastomeres and the
      degree of cellular fragmentation. A total of 242 embryo transfers in which 4
      embryos were transferred were included. Sixty-nine (28.5%) clinical and 62
      (25.6%) viable pregnancies resulted. In all cases 4 embryos were transferred, but
      the number of embryos with even round blastomeres (grade 1) varied from 0 to 4.
      Statistically, there was no correlation between PR and number of grade 1 embryos
      transferred. When 4 grade 1 embryos were transferred, the PR was 33.3 versus
      28.1% when no grade 1 embryos were transferred. There was, however, a statistical
      difference in the implantation rate; a higher frequency of multiple gestations
      occurred when 3 or 4 of the embryos transferred were graded 1:12.7 as compared
      with 6.7% when < or = 2 embryos were grade 1. The significance of the degree of
      cellular fragmentation in the embryos was also assessed. There was no statistical
      difference in the PR according to the number (0-4) of embryos transferred that
      did not have fragments (grade A). When 4 grade A embryos were transferred, the PR
      was 18.2 versus 26.1% when there were no grade A embryos. Neither implantation
      nor multiple birth rates correlated with fragmentation.

PMID- 8529947
TI  - A longitudinal study of maternal serum human chorionic gonadotropin levels during
      pregnancy.
AB  - OBJECTIVE: To determine if pregnant women with normal singletons will continue to
      have elevated serum human chorionic gonadotropin (hCG), given that they had an
      elevated serum hCG in the second trimester. METHODS: Nineteen women with second
      trimester hCG levels > or = 2.0 multiples of the median, and 20 women with second
      trimester hCG levels < 2.0 multiples of the median were the subjects of this
      investigation. All study participants had serum hCG levels repeated during the
      third trimester of pregnancy. We used a chi-square test and Student's t test for
      comparing categorical variables, and the means of continuous variables,
      respectively. RESULTS: Using the criterion of > or = 2.0 multiples of the median
      of the comparison group to define hCG elevation, women with elevated second
      trimester hCG levels were women with normal second-trimester hCG levels (risk
      ratio = 3.9; 95% confidence interval 1.6-9.8; p < 0.001). Adjustment for
      potential confounders did not materially alter the association. CONCLUSION: Women
      with elevated hCG in the second trimester continued to have elevations in the
      third trimester. The persistence of elevated hCG levels in pregnancies
      uncomplicated by fetal anomalies should be evaluated as a clinical marker of
      adverse pregnancy outcomes.

PMID- 8529948
TI  - Measurement of urinary free beta-human chorionic gonadotropin by
      immunoradiometric assay.
AB  - An immunoradiometric assay for free beta-human chorionic gonadotropin (F beta
      hCG) is now available. Measurement of serum F beta hCG has been shown to be
      valuable for the diagnosis of trophoblastic disease and for screening Down's
      syndrome pregnancies. Urine specimens may be preferable to blood samples since
      collection of urine specimens usually are less inconvenient to patients than
      venipuncture. We have evaluated whether the immunoradiometric assay can be
      applicable to urine samples. The assay was sensitive and precise. When urine
      samples were diluted 4-fold or more, the diluted samples gave quantitative
      values, and recovery of beta hCG added to urine samples was satisfactory.
      Creatinine corrected urinary F beta hCG levels correlated with serum F beta hCG
      levels. Thus, the immunoradiometric assay was considered to be applicable to
      urine samples. Serum F beta hCG to hCG ratio has been reported to be important to
      distinguish among normal pregnancies, hydatidiform mole and choriocarcinoma.
      However, urinary F beta hCG to hCG ratio did not significantly correlate with
      serum F beta hCG to hCG ratio. And therefore, the clinical value of urinary F
      beta hCG to hCG ratio should be further investigated.

PMID- 8529949
TI  - Computer analysis of fetal heart rate during induction of labor with oxytocin.
AB  - We observed the influence of commonly used oxytocin infusion for inducing labor
      on the fetal heart rate (FHR). The FHR was analyzed on-line by Sonicaid Computer
      System 8000. There were no statistical changes in all analyzed parameters during
      infusion of oxytocin. Our study shows that the standard dosage of oxytocin used
      for induction of labor has no negative influence on the FHR.

PMID- 8529950
TI  - When is the optimal time for delivery?--Purely from the fetuses' perspective.
AB  - To determine when the extrauterine environment becomes safer than the
      intrauterine environment with respect to fetal (neonatal) life, we analyzed all
      4,896,505 livebirths, all 21,222 stillbirths, and all 7,513 early neonatal deaths
      after 26 weeks gestation that were recorded between 1989 and 1992 in Japan.
      Although the risk of early neonatal death ( < 1 week of age) and of neonatal
      death ( < 4 weeks of age) greatly exceed the risk of stillbirth at 26 weeks of
      gestation, those risks declined sharply by 39 weeks of gestation, then increased,
      while the risk of stillbirth within 1 and 4 weeks exceeded the risks of early
      neonatal death and of neonatal death at and beyond gestational weeks 40 and 38,
      respectively, for a singleton pregnancy. A similar reversal occurred at 37 and 35
      weeks of gestation for multiple pregnancy. Neonates born at 39 and 37 weeks of
      gestation for singleton and multiple pregnancies, respectively, had the best
      outcome. It is concluded that the chance of survival for fetuses reaching 40 and
      37 weeks of gestation for singleton and multiple pregnancies, respectively, were
      higher in the extrauterine than the intrauterine environment in Japan today.

PMID- 8529951
TI  - Endocervical pathogens in women with preterm and term labour.
AB  - The purpose of this study was to compare the endocervical microflora of women in
      preterm and term labour and to determine whether the presence of a specific
      microflora is significantly associated with preterm labor. A prospective study
      was performed in Lithuania among 212 women in preterm labour (latent phase, n =
      110; active phase, n = 102) and among 62 healthy women in term labour.
      Microbiological assessment included cultures for aerobic bacteria, yeasts, and
      Trichomonas vaginalis and direct immunofluorescence reaction for Chlamydia
      trachomatis, Escherichia coli (odds ratio 8.16; 95% confidence interval 1.27
      340.23) and Staphylococcus aureus (odds ratio 7.79; 95% confidence interval 1.21
      325.40) were significantly more often isolated from women in preterm than from
      women in term labour. The prevalence of C. trachomatis was the same in the
      preterm and in the term labour group. The pregnancy outcome during the latent or
      active phase of preterm labour with or without C. trachomatis infection did not
      differ. It is concluded that E. coli and S. aureus are significantly more
      prevalent in endocervical cultures from Lithuanian women in preterm than from
      those in term labour.

PMID- 8529952
TI  - Low birth weight and genital infections. An incident case-referent study.
AB  - In an attempt to elucidate the potential association between genital infections
      and low birth weight (LBW) births, 51 women with LBW neonates were identified and
      compared to 51 women with normal birthweight (NBW) neonates. Both groups were
      matched according to age and parity. All women were subjected to interviews
      regarding socioeconomic background and obstetric history. The were examined
      clinical and tested regarding serum haemoglobin, malaria parasitaemia, syphilis
      and HIV serology. Cultures were taken from the vagina, endocervix, amniotic fluid
      and from various sites of newborn, including the conjunctivae and the stomach and
      from the interior of the placenta. Whilst socioeconomic background factors did
      not differ among cases and referents, previous neonatal death did. Significant
      differences were also found in mid-upper-arm circumference (OR 3.08) and body
      mass index (OR 6.00). The prevalence of alleged risk factors according to the
      antenatal card was similar among cases and referents. Birthweight < 2,000 g was
      significantly more often associated with chorioamnionitis than birthweight
      between 2,000 and 2,499 g (OR 5.46). Bacteriological findings did not show
      significant differences in cases and referents. Haemoglobin values and prevalence
      of malaria parasitaemia were similar as was the neonatal mortality. It is
      concluded that LBW births is difficult to predict by use of alleged risk factors
      in existing antenatal cards.

PMID- 8529953
TI  - Effects of atrial natriuretic peptide and cyclic guanosine monophosphate on
      isolated human myometrial arteries preconstricted by endothelin-1.
AB  - In the present in vitro study we investigated the possible vasorelaxing effect of
      atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) on
      small intramyometrial arteries precontracted by endothelin-1 (ET-1). Myometrial
      biopsies from normotensive pregnant women were obtained during cesarean section
      and arteries of resistance vessel size were dissected and mounted in a tissue
      chamber for isometric registration of contractile tone. In arteries
      preconstricted with ET-1 (10(-8)M), ANP produced a concentration-dependent
      relaxation of 19 +/- 5% (mean +/- SEM) and 27 +/- 7% at concentrations of 10(-7)
      and 3 x 10(-7) M, respectively. cGMP induced a relaxation of 13 +/- 2, 18 +/- 3,
      25 +/- 4 and 30 +/- 7% at concentrations of 10(-5), 10(-4), 3 x 10(-4) and 10(-3)
      M, respectively. Pretreatment with ANP did not attenuate the contraction produced
      by ET-1. We suggest that ANP may have a vasodilating effect on preconstricted
      human uteroplacental vessels. It also provides evidence for the role of other
      endogenous or exogenous vasodilators acting via cGMP-dependent mechanisms in the
      counteraction of ET-1-induced contraction of the myometrial resistance vessels
      during pregnancy.

PMID- 8529954
TI  - Insulin response of women athletes in relation to body fat quantified by magnetic
      resonance imaging.
AB  - We report the glucose and insulin response to a 300-min glucose tolerance test
      among 17 women athletes as compared with 11 normal, nonatheletic controls. Also
      reported is the relationship of the insulin area under the curve as a function of
      percentages of total fat (TF), subcutaneous fat, and internal fat of total volume
      (TV) quantified by magnetic resonance imaging overall and at six regional sites.
      Athletes had a more sensitive insulin response to the glucose tolerance test as
      compared with controls. The insulin area under the curve of athletes and controls
      was significantly (p = 0.05) related to their overall TF/TV%; athletes had
      significantly less TF/TV% compared with the controls.

PMID- 8529955
TI  - Hormone testing in women with adult-onset amenorrhea.
AB  - To assess the clinical utility of routine endocrine testing in women with adult
      onset amenorrhea, charts were identified from 127 women diagnosed with adult
      onset amenorrhea who had a thyroid-stimulating hormone (TSH), follicle
      stimulating hormone (FSH), and prolactin (PRL) level performed. Women who were
      pregnant or previously diagnosed with thyroid disease were subsequently excluded
      and 120 subjects remained. Of the 120 women screened, 12 (0.100) had abnormal FSH
      levels, 9 (0.075) had abnormal PRL levels, and 5 (0.042) had abnormal TSH levels.
      The incidence of an abnormal FSH level (95% CI 0.053, 0.168; p < 0.001) and PRL
      level (95% CI 0.035, 0.138; P = 0.007) was significantly elevated as compared to
      the reference laboratory normal values. However, the incidence of an abnormal TSH
      level in the study population was not statistically different from that of the
      reference laboratory normal values (95% CI 0.014, 0.095, p = 0.88). The
      evaluation of 120 women with adult-onset amenorrhea demonstrated abnormal
      concentrations of FSH, PRL and TSH in 10, 7.5 and 4.2% of patients, respectively.
      A rank ordering of these endocrine tests may be useful when evaluating women with
      adult-onset amenorrhea.

PMID- 8529957
TI  - Prevalence and significance of HER-2/neu amplification in epithelial ovarian
      cancer.
AB  - Amplification of the HER-2/neu oncogene was assessed in 80 cases of epithelial
      ovarian tumors using differential polymerase chain reaction. HER-2/neu gene was
      amplified in 22 of 46 invasive cancers (48%) and in 5 of 34 borderline cancers
      (15%), but none of the 20 specimens of normal ovaries showed amplification. THis
      difference is statistically significant (p = 0.00004). The incidence of HER-2/neu
      amplification in late stage (III-IV, 77%) was significantly higher than that in
      early stage (I-II, 21%) in invasive epithelial carcinoma (p = 0.0004). There was
      no correlation between HER-2/neu amplification and cell type or grade of tumor.
      In cases of ovarian tumors of borderline malignant potential, the amplification
      of HER-2/neu was not correlated with clinicopathologic features. Follow-up with a
      mean of 22 months (6-50 months) was available for 39 cases of invasive ovarian
      cancers and all 34 borderline ovarian cancers. The incidence of HER-2/neu
      amplification in the invasive cancer and borderline cancer patients who were
      alive with disease was 50 and 50%, and is not statistically different from that
      in the patients who were alive with no evidence of disease (p = 0.662 and 0.345,
      respectively). The incidence of amplification in the invasive cancers of patients
      who died of the disease (86%) was higher than that in the patients who were still
      alive (44%), but the difference is not statistically significant (p = 0.175).
      This study supports the association of HER-2/neu amplification with progression
      of invasive ovarian cancer. It also suggests that HER-2/neu amplification may be
      an adjunctive prognostic factor of invasive epithelial ovarian cancer, shown to
      be associated with an unfavorable clinical course. In addition, HER-2/neu
      amplification occurs relatively infrequently in early invasive and borderline
      ovarian cancers, making it unlikely that such amplification is a general early
      event in ovarian carcinogenesis.

PMID- 8529956
TI  - Clonal determination of uterine leiomyomas by analyzing differential inactivation
      of the X-chromosome-linked phosphoglycerokinase gene.
AB  - To investigate the clonality of uterine leiomyomas, we developed a PCR-based
      method involving the differential inactivation of the X-chromosome-linked
      phosphoglycerokinase (PGK) gene. Small DNA samples of 22 leiomyomas from 9
      Japanese patients, showing heterozygosity at the BstXI site of the PGK gene, were
      digested with the methylation-sensitive restriction enzyme HpaII. Only the
      inactive (methylated) PGK gene allele was selectively amplified by PCR followed
      by digestion with BstXI and electrophoresis. All leiomyoma samples consisted of a
      single type of inactive allele, even though alleles were detected that were
      specific to each nodule. The results indicated that all leiomyoma nodules were
      unicellular in origin but independently generated in the uterus.

PMID- 8529958
TI  - A case of cervical pregnancy treated with methotrexate.
AB  - A case of cervical pregnancy was treated successfully with methotrexate and
      folinic acid. Serial beta-HCG and sonography were used to diagnose the pregnancy
      and to monitor the therapy. Treatment was successful and the patients
      reproductive capability was preserved.

PMID- 8529959
TI  - Ureteral obstruction caused by endometriosis.
AB  - The diagnosis of ureteral obstruction caused by endometriosis can be difficult.
      We present a 51-year-old multiparous Japanese women who had undergone right
      salpingo-oophorectomy at the age of 19 years. She underwent total hysterectomy,
      left salpingo-oophorectomy, and adhesiotomy of the right ureter after the
      diagnosis of myoma uteri and endometriosis was made. Microscopic examination of
      the surrounding resected tissue confirmed the typical endometriotic origin. In
      addition to intravenous and retrograde pyelography, computerized tomography was
      useful to establish the diagnosis of ureteral obstruction caused by an extrinsic
      mass of endometriotic tissue.

PMID- 8529960
TI  - [Inhibition of integrin function prevents restenosis following vascular injury].
AB  - Activation of platelets leads to thrombosis and secretion of PDGF and other
      stimulators of smooth muscle cell (SMC) migration/proliferation, resulting in
      neointima formation. RGD-containing peptides can prevent the binding of several
      integrins including alpha II b/beta 3 (GP II b/III a) in platelet aggregation and
      alpha v/beta 3 in smooth muscle cell migration, both of which are involved in
      neointima formation. Thrombus formation was measured by transillumination and
      image analysis at 30 min, 24 hr and 72 hr after vascular injury and neointima was
      quantified in the same carotid arteries in hamsters at 2 weeks. The proliferation
      index of SMC was determined at 1, 3, 5, 7, and 14 days after denudation following
      four injections of BrdU. After treatment with G4120 at a dose of 100
      micrograms/kg/hr, both thrombus size (89.2 +/- 5.5% inhibition vs control) and
      neointima formation (60.2 +/- 6.6% inhibition vs control) were significantly
      reduced. Pooling individual data for treated hamsters with those obtained for the
      untreated animals still resulted in a significant correlation (r = 0.64, n = 47,
      P < 0.001). Reduction of neointima by G4120 is linked to a lower percentage of
      proliferating cells in the media and neointima from 16.5 +/- 9.7% on day 1
      (media) and 20.2 +/- 7.3% on day 5 (intima) in the control animals to 9.9 +/-
      6.1% on day 1 (media) and 13.4 +/- 9.0 on day 5 (intima) in the G4120 treated
      animals. In conclusion, inhibition of integrin function results in reductions of
      thrombus and neointima formations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529961
TI  - [Hyperpolarization-relaxation coupling in vascular smooth muscle].
AB  - Studies performed to elucidate the inhibitory mechanisms of the hyperpolarization
      induced by K+ channel openers on the Ca2+ movements and force of contraction
      produced by either the stimulation of thromboxane A2 receptors or depolarization
      with high KCl have shown the following: When the plasma membrane is
      hyperpolarized by K+ channel openers, voltage-dependent L-type Ca2+ channels are
      deactivated and the influx of Ca2+ is decreased, as is the case with the KCl
      induced Ca2+ influx. The hyperpolarization of the plasma membrane also has other
      inhibitory effects on phospholipase C, a membrane-associated enzyme activity. The
      IP3 production and IP3-induced Ca2+ release from intracellular stores, which is
      related to the stimulation of the agonist receptors, are inhibited by the
      hyperpolarization of the plasma membrane by K+ channel openers. Recently, we
      showed that the Ca2+ sensitivity of the contractile elements was voltage
      dependent. Furthermore, membrane hyperpolarization induced by various K+ channel
      openers relaxed canine coronary arteries more profoundly than decreased [Ca2+]i.
      Thus, the membrane voltage may regulate intracellular enzyme activities,
      including contractile elements. Therefore, this new facet of signal transduction
      should be considered in the control of vascular tone. The evolutional
      relationships of various K+ channels are also discussed.

PMID- 8529962
TI  - [Gastrin/CCK-B receptor antagonists for a novel antiulcer agent].
AB  - Gastrin plays an important role in gastrointestinal functions such as gastric
      secretion and mucosal growth. The hypergastrinemia that results from long-term
      treatment with proton pump inhibitors and histamine H2-receptor antagonists
      induces hyperplasia of enterochromaffin-like (ECL) cells and increases the
      secretory response to pentagastrin (acid rebound). Recently, potent and selective
      gastrin/CCK-B-receptor antagonists, L-365,260, PD136450 and YM022, have been
      developed. These compounds inhibit basal and meal-stimulated acid secretion as
      well as pentagastrin-stimulated acid secretion in rats and dogs. Long-term
      treatment with gastrin/CCK-B-receptor antagonists does not cause hyperplasia of
      ECL cells and acid rebound at all. Moreover, they prevent hyperplasia and acid
      rebound induced by proton pump inhibitors and histamine H2-receptor antagonists.
      Therefore, gastrin/CCK-B-receptor antagonists are suggested to be novel antiulcer
      and antisecretory agents without potential for acid rebound, hyperplasia and
      carcinoid.

PMID- 8529963
TI  - [Prostacyclin mimetics with non-prostanoid structures].
AB  - In searching for new drugs, we have developed receptor binding assays for
      prostanoids. Among the various compounds that we have tested, we have found that
      hydronaphthalene derivatives can interact with some prostanoid receptors.
      Modification of such compounds produced several pure prostacyclin agonists (ONO
      AP-227 and ONO-AP-437) and a unique prostacyclin agonist with inhibitory activity
      against thromboxane synthase (ONO-AP-500-02). These compounds showed specific
      binding to the IP receptor with Ki values less than 0.2 microM, without binding
      to EP and TP receptors. These compounds also inhibited human platelet aggregation
      with IC50 values of 0.03-0.24 microM. These compounds inhibited ex vivo platelet
      aggregation in dogs or rats in the dose range of 1 to 30 mg/kg. Furthermore, ONO
      AP-500-02 inhibited ex vivo thromboxane formation at doses similar to those
      inhibiting platelet aggregation in rats. These results, taken together, suggest
      that chemical syntheses of compounds targeting prostanoid receptors can produce
      unique prostanoid agonists or antagonists, and rational syntheses might be
      possible for compounds with different pharmacological actions such as inhibition
      of thromboxane synthase.

PMID- 8529965
TI  - [Selective type III phosphodiesterase inhibitor as an antithrombotic agent].
AB  - In platelets, an increase in cAMP levels potently inhibits aggregation and
      release reactions. Cilostazol is an antiplatelet agent that increases
      intracellular cAMP levels by selective Type III phosphodiesterase (PDE)
      inhibition. The characteristics of cilostazol are presented in this review.
      Adenylate cyclase potentiator also shows strong inhibitory actions on platelet
      functions, but a number of reports suggest that the continuous use of an
      adenylate cyclase potentiator may lead to a reduction of drug efficacy. On the
      other hand, such an action has not been seen with cilostazol even after
      continuous administration of cilostazol (100 mg/kg) for two weeks in rats, which
      may be due to a feature of this drug, namely, inhibitory actions on PDE.
      Inhibitory actions of cilostazol on PDE are specific: strong inhibition (IC50 =
      0.19 microM) against Type III PDE that comprises most of the PDE activities in
      platelets and weak inhibition against Type IV PDE that comprises most of the PDE
      activities in endothelial cells (ECs). This fact (i.e., specificity of
      cilostazol) brought about important results when the drug reacted in the presence
      of both platelets and blood vessels. A non-specific PDE inhibitor such as IBMX
      increases cAMP and decreases PGI2 synthesis in ECs, but such a phenomenon was not
      seen with cilostazol. The inhibitory actions of cilostazol on platelet functions
      were potently enhanced in the presence of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8529964
TI  - [Discovery and pharmacological properties of selective neurokinin-receptor
      antagonists, FK224 and FK888].
AB  - In order to create a new drug for the treatment of respiratory diseases, such as
      asthma and chronic bronchitis, having a novel therapeutic mechanism, we have been
      trying to develop new compounds with neurokinin (NK)-receptor antagonistic
      effects. We used [3H]-substance P binding to guinea pig lung membrane for the
      first screening system and successfully discovered FK224 from a fermentation
      product and FK888 from chemical design studies using an octapeptide antagonist (D
      Pro4,D-Trp7,9,10) SP4-11 as the parent compound. FK224 and FK888 showed different
      selectivities against the NK-receptor subtypes (NK1, NK2, NK3); FK888 was a
      highly potent NK1-selective antagonist, and FK224 was a NK1 + NK2 dual receptor
      antagonist. Neither compound had any activity on the NK3 receptor. In the in vivo
      experiments, FK224 and FK888 significantly inhibited the constriction and plasma
      extravasation in the airway induced by agonist injection. These compounds also
      showed inhibitory effects on the airway response induced by capsaicin and
      antidromic stimulation of vagus nerves. Furthermore, FK224 and FK888 were
      effective on the mucus secretion in the airway and the cough reflex induced by
      citric acid challenge. There were some differences in the effects of FK224 and
      FK888 in the in vivo experiments, and it was suggested that the NK1 receptor and
      NK2 receptor were mainly involved in neurogenic inflammation and airway
      constriction, respectively. FK224 and FK888 are now undergoing clinical studies
      to test the effectiveness of a NK antagonist in human respiratory diseases.

PMID- 8529967
TI  - [Structure and pharmacological activity of pectic polysaccharides from the roots
      of Bupleurum falcatum L].
AB  - Several pharmacological activities have been observed in pectic polysaccharides
      which were isolated from Chinese herbs containing Kampo medicines. We found two
      different bioactive pectic polysaccharides, bupleuran 2IIb and 2IIc, from the
      roots of Bupleurum falcatum. These bioactive pectic polysaccharides were
      comprised of an alpha (1-->4) linked galacturonan region, a ramified region that
      consists of a rhamnogalacturonan core substituted neutral sugar chains as the
      side chains and a rhamnogalacturonan II (RG II)-like region containing unique
      sugars such as 3-deoxy-manno-2-octulosonic acid (KDO). In order to understand the
      pharmacological activity of pectic polysaccharides on the molecular level, we
      have elucidated the essential carbohydrate structure for the expression of each
      pharmacological activity and their mode of actions. The ramified region in
      bupleuran 2IIb induced Fc receptor up-regulation in macrophages by a mechanism
      dependent on an increase of intracellular Ca2+, followed by the enhancement of
      immune complex clearance, whereas bupleuran 2IIc, which mainly consists of a
      partially branched galacturonan region, showed potent anti-ulcer activity. The
      major mechanism of its mucosal protection was suggested to be due to anti
      secretory activity on acid and pepsin, its ability to provide a protective
      coating and radical scavenging effect. The future problems were also discussed in
      order to develop pectic polysaccharides as medicines.

PMID- 8529966
TI  - [Functional significance of diazepam binding inhibitor (DBI) in establishment of
      alcohol dependence].
AB  - This review summarizes the data showing the possible involvement of an endogenous
      ligand for benzodiazepine (BDZ) receptors, diazepam binding inhibitor (DBI), in
      the development of alcohol dependence. The expression of cerebral DBI mRNA
      significantly increased in EtOH-inhaled and EtOH-withdrawn mice in comparison
      with that in EtOH-untreated mice, whereas the DBI mRNA level was not altered
      after a single administration of EtOH. After EtOH-withdrawal, this increase in
      the DBI mRNA expression in the mouse cerebral cortex diminished over 14 days
      despite the disappearance of withdrawal signs within 2 days after the withdrawal
      of EtOH. Simultaneous administration of flunitrazepam, a BDZ receptor agonist,
      with EtOH completely abolished the EtOH-induced increase in DBI mRNA expression.
      These results lead to the assumption that the changes in the expression of
      cerebral DBI mRNA induced by continuous EtOH treatment may be involved in the
      establishment of alcohol dependence, and such changes may be also regulated by
      BDZ receptors.

PMID- 8529968
TI  - Comparative study of oestrogen excretion in female New World Monkeys: an overview
      of non-invasive ovarian monitoring and a new application in evolutionary biology.
AB  - Oestrogen was measured in urine samples collected from captive females
      representing 7 species of New World monkey to provide an overview of the
      applicability of such formation in the noninvasive monitoring of ovarian function
      and to assess the potential applicability of such information in phylogenetic
      studies. Species available for study were the pygmy marmoset, common marmoset,
      red-bellied tamarin, cotton-top tamarin, golden lion tamarin, Goeldi's monkey and
      the owl monkey. Oestrone conjugates were measured in serially collected urine
      samples to demonstrate ovarian cyclicity. Urine samples obtained during the
      luteal phase were subjected to HPLC to identify immunoreactive oestrogens;
      oestrone and oestradiol-17 beta accounted for almost all of the immunoreactive
      oestrogen detected while oestriol content was negligible. Urine samples obtained
      during the follicular phase and luteal phase were subjected to glucuronidase
      hydrolysis, sulphatase hydrolysis and acid solvolysis, which revealed that the
      major immunoreactive oestrogen metabolite was: (1) oestradiol sulphate in the
      pygmy marmoset and common marmoset, (2) residual oestradiol in the red-bellied
      tamarin, (3) residual oestradiol and oestrone glucuronide in the cotton-top
      tamarin, and (4) oestrone glucuronide in the golden lion tamarin, Goeldi's monkey
      and owl monkey. A phylogenetic tree based on the above shifts in oestrogen
      excretion suggested that clawed New World monkeys are specialized and that the
      lineages leading to the study species split off in the following order: Goeldi's
      monkey, golden lion tamarin, cotton-top tamarin, red-bellied tamarin, common
      marmoset and pygmy marmoset.

PMID- 8529969
TI  - Function of copulatory vocalizations in mate choice by females of Japanese
      macaques (Macaca fuscata).

PMID- 8529970
TI  - Differential excretion of urinary oestrogen by breeding females and daughters in
      the red-bellied tamarin (Saguinus labiatus).

PMID- 8529971
TI  - Sexual selection and ejaculatory frequencies in primates.

PMID- 8529972
TI  - Triadic male-female-infant relationships and bridging behaviour among Tibetan
      macaques (Macaca thibetana).

PMID- 8529973
TI  - Population status and conservation of red howling monkeys and white-fronted
      capuchin monkeys in Trinidad.

PMID- 8529974
TI  - Field observation of a group of Geoffroy's marmosets mobbing a Margay cat.

PMID- 8529975
TI  - [Combined plant extract preparations--questionable "purification"].

PMID- 8529976
TI  - [Benign colonic ulcer. Case report and differential diagnosis].
AB  - Benign ulcers of the colon are a rare source of colorectal bleeding. The present
      case report describes a woman who experienced several episodes of bleeding from
      an NSAID-induced ulcer of the caecum. The differential diagnosis of colonic
      ulcers is discussed.

PMID- 8529977
TI  - [Transient ischemic attacks as a warning signal. As stroke precursor it is often
      underestimated].

PMID- 8529978
TI  - [General practice and patient-oriented medical education. Practicum for
      "Introduction to clinical medicine (with patient examination)"].

PMID- 8529979
TI  - [Dermatomycoses. 12: Mycoses of the genital region--clinical picture and
      differential diagnosis].

PMID- 8529980
TI  - [Vaccines against AIDS finally in sight? Vaccination campaigns in China and
      Uganda in preliminary stages].

PMID- 8529982
TI  - [Molecular mechanisms in Alzheimer disease].
AB  - With the aim of investigating the transport and metabolism of amyloid precursor
      protein (APP) in neurons, APP was expressed in neurons from the hippocampus using
      the Semliki-Forest virus vector. It was found that APP in the cell migrates from
      the nucleus into the axons and from there into the dendrites. During this
      migration, human APP is split at the total of six places, resulting in particular
      in the formation of beta A4 amyloid peptide. A greater production of beta A4 was
      observed in persons with inherited forms of Alzheimer's disease. In rat APP, in
      contrast, the amount of beta A4 secreted is clearly reduced. These findings
      suggest that beta A4 plays a central role in the genesis of the disease. The
      experimental methods open up the possibility of developing and testing
      therapeutic approaches to Alzheimer's disease.

PMID- 8529981
TI  - [Vertebral replacement in palliative tumor therapy. Possible surgical procedures-
      significant improvement in quality of life].
AB  - Complications associated with spinal metastases encompass not only pain, but
      often neurological deficits and possibly even paralysis due to transverse
      lesions. The differential indication for dorsal, ventral and combined surgical
      procedures depends on the nature and extent of the tumor, and the life expectancy
      and general state of health of the patient. Surgery must be carried out in good
      time, before additional damage to the spinal cord occurs. In recent years, 20
      patients have been treated by GHG-vertebral body replacement. In 19 of these
      patients, pain was considerably improved. All patients were able to walk
      following surgery. Preoperative neurological deficits disappeared, in 9 of 13
      patients resulting in a major improvement in the patients' quality of life.

PMID- 8529983
TI  - [Rational thyroid screening--what is reliable? Basal TSH values and ultrasound
      morphologic criteria as screening parameters].

PMID- 8529984
TI  - [Dermatomycoses. 13: Mycoses of the genital region--therapy and follow-up].

PMID- 8529985
TI  - [DMSO in patients with active gonarthrosis. A double-blind placebo controlled
      phase III study].
AB  - BACKGROUND: For the patient, the most important aspect of gonarthrosis is pain
      and the associated impairment of movement.-- METHOD: In a randomized, placebo
      controlled, double-blind study involving 112 patients (56 in each of the two
      groups test substance and placebo) the efficacy and tolerability of DMSO gel 25%
      applied over a period of three weeks were investigated in comparison with
      placebo. In addition to an assessment by the doctor of pain under loading while
      going about daily activities, rest pain, pain on palpation and of loss of
      mobility, the patient also kept a pain diary.-- RESULTS: In comparison with the
      gel base used as placebo, percutaneous treatment with DMSO proved to have a
      clinically relevant analgesic effect on the intensity of loading pain during
      everyday activities (p = 0.019). A positive effect of DMSO was also seen for pain
      intensity at rest (p = 0.015) and pressure pain (p = 0.029). The pain diary also
      reflected these observations. No serious adverse events or changes in laboratory
      values were observed.

PMID- 8529986
TI  - [Granulomatous vasculitis of the CNS as a complication of herpes zoster
      ophthalmicus].
AB  - A 61-year old man with a history of arterial hypertension suffered a left HZO,
      and was treated with acyclovir. Three weeks later he suddenly developed moderate
      left hemiparesis particularly of the leg, severe paresis of the right leg,
      aphasia and somnolence. Treated with IV acyclovir and high-dose corticosteroids
      deterioration of the right hemiparesis was apparent. Serological and CSF-studies
      showed acute varicella-zoster virus infection with intrathecal antibody synthesis
      (antibody specificity index 2.7). On the third day CT scan revealed infarctions
      in the territory of both anterior cerebral arteries, at the fifth day
      additionally left striatocapsular infarction. Selective carotid arteriogram
      showed bilateral occlusions of anterior cerebral arteries in their proximal
      segment. With a mean delay of seven weeks granulomatous vasculitis is a rare
      complication of HZO, leading commonly to ischemic infarctions in the region of
      the middle cerebral artery. Trigeminovascular connections are the probable
      pathway of virus-transmission from the trigeminal nerve to ipsilateral branches
      of the circle of Willis. Because of the presumed pathogenesis immediate therapy
      with high-dose corticosteroids and acyclovir is justified.

PMID- 8529987
TI  - [Torticollis spasmodicus as a manifestation of tardive dystonia].
AB  - Tardive dystonia is a subtype of tardive dyskinesia which is rarely recognised
      and diagnosed. Tardive dystonia occurs clearly less frequently than oro-bucco
      lingual dyskinesia (approx. 1 vs. 20%). We present a case report and give a
      survey on the characteristics of tardive dystonia, its differential diagnosis and
      treatment as described in literature.

PMID- 8529988
TI  - [Schizophrenia and quality of life--sex-specific aspects].
AB  - Empirical studies show that schizophrenic women and men differ in psychological
      as well as social characteristics. In women the course of illness and objective
      life situation seem to be more favourable. In studies on the subjective quality
      of life in psychiatric patients, gender-specific aspects have hardly been
      considered so far. Some results indicate that women--contrary to women of the
      general population--are more content than male psychiatric patients. The
      systematic inclusion of gender-specific aspects in quality of life studies might
      clarify how quality of life is influenced in psychiatric patients. It might also
      contribute to designing psychiatric care in a way that specific sources of
      satisfaction are made use of.

PMID- 8529989
TI  - [Amnestic syndrome--research update].
AB  - Amnesia characterized by a severe impairment of the memory without a loss of
      consciousness is one of the 'classical' organic brain syndromes. According to the
      course, further symptoms and the circumstances of appearance, several subtypes
      can be differentiated: transient global amnesia, posttraumatic amnesia,
      Korsakow's psychosis, and psychogenic amnesia. Many disorders may cause amnesia.
      Guidelines for the differentiation of the underlying disorders and therapeutic
      strategies are discussed.

PMID- 8529990
TI  - [The dysthymia concept: current and historical aspects--an overview].
AB  - The article reviews the historical development of the understanding of dysthymia
      from C. F. Flemming (1844) to DSM-IV and to Akiskal's concepts. Recent results on
      epidemiology, comorbidity, neurobiology, familial patterns, clinical course,
      psychological characteristics, psycho- and pharmacotherapy of dysthymia are
      discussed. Although present concepts of dysthymia have led to results of high
      scientific and clinical relevance, the classification of chronic depression and
      their relation to both personality disorders and affective psychoses need further
      clarification. The development of dysthymia reflects the differences between
      Anglo-American operational psychiatric systems and the rich tradition of
      psychopathology in German-speaking psychiatry.

PMID- 8529991
TI  - [Physiopathology and treatment of diabetic retinopathy].

PMID- 8529992
TI  - [Primary biliary cirrhosis--antimitochondrial antibody and the reactive
      antigens].

PMID- 8529993
TI  - The contraction of small arteries in the perimetrium by presurgical medication
      with the luteinizing hormone-releasing hormone agonist to patients with
      leiomyomas: an electron and immunoelectron microscopy.
AB  - The remarkable contraction of small arteries occurred in the perimetrium of the
      uteri with leiomyomas by a presurgical medication P6th the luteinizing hormone
      releasing hormone (LHRH) agonist (buserelin). The contracted vessels showed a
      significant increase in number of the Weibel-Palade (WP) bodies which
      occasionally underwent the degranulation and the discharge in a manner of
      exocytosis. By immunoelectron microscopy, localizations of endothelin (ET)-1
      immunoreactive gold particles on the WP bodies as well as on cisterns of the
      rough endoplasmic reticulum (rER) and Golgi apparatus were pronounced in the
      buserelin-medicated group when compared to the non-medicated one. These findings
      indicate that the increase of the WP bodies storing ET-1, of which synthesis in
      the rER-Golgi system enhances, predominantly occurred in the small arteries in
      the perimetrium by the buserelin-medication prior to the hysterectomy. ET-1,
      released into the subendothelial layer, seems to play an important role in the
      contraction of the vascular media in a manner of paracrine.

PMID- 8529994
TI  - [Pallidotomy in patients with Parkinson disease].

PMID- 8529995
TI  - Paracentric inversions: a review.
AB  - This review of paracentric inversions in man includes what we know of the
      behaviour and reproductive consequences of paracentric inversions from other
      species. Observations of naturally occurring inversions in several species of
      plants and animals and results of experiments with mutagenically induced
      inversions in the mouse are discussed. From a review of 184 cases, it is
      concluded that most of the paracentric inversions in man are harmless and that
      the risk of heterozygotes having a child with an unbalanced karyotype is low.
      However, in some cases, it is difficult, if not impossible, to distinguish
      between a paracentric inversion and a paracentric insertion, the risk in the
      latter case being about 15%. Caution is also necessary in interpreting the
      results of prenatal diagnosis for heterozygotes of paracentric inversions,
      because of the possibility of a variety of unpredictable unbalanced chromosome
      products.

PMID- 8529996
TI  - Susceptibility of heterochromatin to aphidicolin-induced chromosomal breakage.
AB  - The distribution of aphidicolin-induced chromosomal lesions was analyzed to
      determine the relative breakage susceptibility of euchromatin and heterochromatin
      in the cactus mouse, Peromyscus eremicus. The observed breakage was tested
      against expected distributions corresponding to the karyotypic proportions of
      autosomal euchromatin, autosomal heterochromatin, X-chromosomal euchromatin, and
      X-chromosomal heterochromatin. The distribution of induced breakage was
      independent of sex but dependent on the individual. In all individuals, there was
      a highly significant (P < < 0.0001) deficiency in the number of breaks observed
      as compared to expected in autosomal heterochromatin. Sparse observations in the
      X chromosome and the absence of breaks in the Y chromosome precluded valid
      statistical tests of the sex-chromosomal distribution of induced breakage. These
      data indicate that the autosomal heterochromatin of Peromyscus is resistant to
      aphidicolin-induced chromosomal breakage and argue against a simple relationship
      between late replication and a general mechanism for chromosomal fragility.

PMID- 8529998
TI  - Interaction between ABO blood groups and ADA genetic polymorphism during
      intrauterine life. A comparative analysis of couples with habitual abortion and
      normal puerperae delivering a live-born infant.
AB  - A total of 203 couples with unexplained habitual abortions and 364 consecutive
      normal puerperae along with their live-born babies were studied. The analysis of
      wife-husband joint ABO blood group distribution in couples with habitual abortion
      showed an excess of A incompatible mating type and a defect of B incompatible
      type as compared with expected proportions assuming random mating. The joint wife
      husband ABO blood group distribution was further analysed in relation to the
      adenosine deaminase (ADA) genotype. A defect of O-A and A-O couples when the wife
      carries the ADA*1/*1 genotype and the husband carries the ADA*2 allele, and a
      defect of O-O and A-A when the wife carries the ADA*2 allele were observed. In
      the sample of normal puerperae, analysis of the joint mother-newborn ABO
      distribution in relation to the ADA genotype showed a pattern similar to that
      observed in couples with habitual abortion, i.e. there is a defect of O-A and A-O
      when the mother carries the ADA*1/*1 genotype and the newborn carries the ADA*2
      allele and a defect of O-O and A-A types when the mother carries the ADA*2
      allele. Altogether the data suggest an early loss of O-A and A-O zygotes when
      they carry the ADA*2 allele and an early loss of O-O and A-A zygotes when the
      mother carries the ADA*2 allele resulting in a deficit of these zygotic classes
      among both spontaneously aborted fetuses and live-born infants. The pattern of
      association observed in the mother-fetus type O-A (incompatible according to
      conventional terminology) appears similar to that observed for the reciprocal A-O
      type (compatible according to conventional terminology). Therefore strictly
      conventional immunological mechanisms cannot explain the whole pattern of
      associations. Cell to cell intereactions involving ABO antigens may have an
      important role at implantation: ADA, through the control of local adenosine
      concentration, could modulate these interactions influencing the probability of
      successful implantation.

PMID- 8529997
TI  - Evaluation of G-to-A substitution in the apolipoprotein A-I gene promoter as a
      determinant of high-density lipoprotein cholesterol level in subjects with and
      without cholesteryl ester transfer protein deficiency.
AB  - The effect of a polymorphism, guanine (G) to adenine (A) substitution in the
      promoter of apolipoprotein A-I gene at a position 78 bp upstream of the
      transcription initiation site, on the serum high-density lipoprotein (HDL)
      cholesterol level was studied in 168 Japanese subjects with HDL-cholesterol
      levels ranging from 26 to 171 mg/dl. Considering the significant effect of
      cholesteryl ester transfer protein (CETP) on the HDL-cholesterol level and the
      common occurrence of its deficiency, we performed statistical analyses separately
      for two groups: one without CETP deficiency (n = 126) and the other with CETP
      deficiency (n = 42). In the group without CETP deficiency, in which the numbers
      of G/G, G/A, and A/A genotypes were 92 (73.0%), 28 (22.2%), and 6 (4.8%),
      respectively, the frequency of the A allele in the subjects with HDL-cholesterol
      levels of > or = 70 mg/dl did not differ from subjects with HDL-cholesterol
      levels of < or = 69 mg/dl, irrespective of gender: 0.154 and 0.145 in males, and
      0.182 and 0.174 in females, respectively, for the > or = 70 mg/dl and < or = 69
      mg/dl groups. Additionally, the HDL-cholesterol levels for the subjects with the
      G/G genotype did not differ from those for the subjects with the A allele: 64 +/-
      22, 58 +/- 14, 77 +/- 14 and 62 +/- 16 mg/dl, respectively, for the G/G, G/A,
      A/A, and G/A + A/A in males, and 72 +/- 18, 74 +/- 24, 63 +/- 4, and 73 +/- 23
      mg/dl in females. For the group with CETP deficiency, in which the numbers of G/G
      and G/A + A/A genotypes were 25 (59.5%) and 17 (40.5%), the HDL-cholesterol
      levels also did not differ: 98 +/- 24 mg/dl and 99 +/- 30 mg/dl, respectively,
      for the G/G and G/A + A/A genotypes. Thus, there is no evidence that the
      polymorphism has any effect on serum HDL-cholesterol levels regardless of CETP
      status. We conclude that the G-to-A substitution in the promoter of
      apolipoprotein A-I gene does not significantly alter serum HDL-cholesterol level.

PMID- 8530000
TI  - Complement component C3: molecular basis of the C3*S025 variant and evidence for
      molecular heterogeneity of other variants.
AB  - Complement component 3 (C3) is the central molecule of the complement system. It
      displays a number of polymorphic variants with, as yet, unclear functional
      consequences. We have investigated a number of rare C3 variants by PCR-SSCP
      (polymerase chain reaction-single strand conformation polymorphism) analysis and
      could identify the molecular basis of a C3*S025 variant. The decreased
      electrophoretic mobility of this protein is caused by the exchange of a neutral
      serine residue to an arginine residue (positively charged). This exchange is
      unlikely to have functional consequences as it maps to the C-terminus of the
      alpha-chain. C3 variants appear to have originated from various independent
      mutations as we could not detect this mutation in different allotypes.

PMID- 8529999
TI  - A 100-kb physical and transcriptional map around the EDH17B2 gene: identification
      of three novel genes and a pseudogene of a human homologue of the rat PRL-1
      tyrosine phosphatase.
AB  - In this paper, we describe the physical map and transcriptional organisation of a
      100-kb region with the BRCA1 locus at 17q12-21. Using the cDNA of the EDH17B2
      gene as a probe, we screened a human genomic cosmid library. Positive cosmid
      clones were aligned and a contig around the EDH17B2 gene was established,
      expanding the previously reported map. In order to identify genes located in this
      region, we used the cosmid inserts to select cDNAs from a human ovarian cDNA
      library. Among the clones identified, cDNA OV-1 corresponds to a human homologue
      of a rat PRL-1 tyrosine phosphatase gene that shows enhanced expression during
      hepatic regeneration and in some tumour cell lines. Neither the OV-1 nor the PRL
      1 protein shares strong homology with any previously characterised
      phosphotyrosine phosphatase, suggesting that they probably belong to a new
      phosphatase family. In an attempt to characterise the OV-1 gene, we found that
      the genomic sequence present on chromosome 17 probably corresponds to a
      nonfunctional copy of the gene, as it contains several sequence changes that
      disrupt the potential coding information of the gene. Three other cDNAs,
      corresponding to unrelated genes, were also identified and characterised. They
      did not reveal striking homologies in database sequence comparison and therefore
      represent new genes localised on chromosome 17q, in a region that frequently
      shows loss of heterozigosity in sporadic breast and ovarian cancers.

PMID- 8530001
TI  - Neonatal screening for cystic fibrosis: result of a pilot study using both
      immunoreactive trypsinogen and cystic fibrosis gene mutation analyses.
AB  - We have evaluated a two-tier neonatal cystic fibrosis (CF) screening of
      immunoreactive trypsinogen (IRT) followed by CFTR gene mutation analysis using a
      systematic scanning of exons 7, 10, and 11, and, if necessary, by direct DNA
      sequencing. Over an 18-month period we screened 32,300 neonates born in the
      western part of Britanny. The first tier, involving IRT screening at 3 days of
      age, utilizes a low elevation of the trypsinogen level (600 ng/ml), which is
      highly sensitive. The second tier, which corresponds to the exhaustive screening
      for mutations in three exons of the gene, is highly specific for this population
      (Britanny). The false positive rate is very low, and no false negatives have been
      reported to date. This strategy has allowed the identification of five novel
      alleles (V322A, V317A, 1806 del A, R553G, G544S).

PMID- 8530002
TI  - A splicing mutation, a nonsense mutation (Y167X) and two missense mutations
      (I159T and A209V) in Spanish patients with ornithine transcarbamylase deficiency.
AB  - Four novel mutations are identified in the ornithine transcarbamylase (OTC) gene,
      in four patients with OTC deficiency (an X-linked disorder). The mutations
      represent three different categories: missense (Ile159Thr and Ala209Val),
      nonsense (Tyr167Stop), and causing inefficient splicing (G-->A in the first
      intronic base) with associated aberrant splicing. They are located in exons 5,
      and 6, and in intron 3. Two of the mutations arose de novo in the patients, and
      only one mutation occurs at a CpG site. The nonsense and the splicing mutation
      cause, respectively, lethal early onset and non-lethal, delayed early onset
      clinical presentations in males. Our results confirm for Spain the high genotypic
      heterogeneity of OTC deficiency.

PMID- 8530003
TI  - Influence of transcription and replication on the in situ resolution of
      immunoglobulin heavy-chain constant region genes: an interphase cytogenetics
      analysis.
AB  - An interphase cytogenetics analysis was performed to investigate whether
      replication and transcription could influence in situ resolution of
      immunoglobulin (Ig) heavy chain constant region genes. A plasmid probe
      recognizing five C gamma segments separated by known linear DNA distances was
      hybridized in situ and visualized by digital fluorescence microscopy. In
      interphase nuclei from phytohemagglutinin (PHA)-stimulated lymphocytes, the gamma
      genes were resolved as one to three signals per allele in the majority of nuclei,
      whereas in a minority, complex patterns of several signals per allele could be
      observed. The latter were restricted to nuclei in an early stage of the S phase,
      as assessed by hybridization experiments performed in cells grown in the presence
      of bromodeoxyuridine. To investigate whether the in situ resolution of the C
      gamma segments could vary as a function of the transcription activity of the
      locus, the C gamma probe was subsequently hybridized to nuclei from a mature B
      cell line (JVM-2), which produces gamma transcripts as shown by in situ RNA
      hybridization experiments. Primary human fibroblasts were further used as
      representative of a non-lymphoid cell type with transcriptionally inactive Ig
      genes. When Gl nuclei from the three cell types were compared in terms of the in
      situ resolution of the C gamma locus, JVM-2 cells were found to include the
      highest percentage of higher resolution patterns (three to five signals per
      allele in 28% of nuclei), fibroblasts the lowest (three signals per allele, 2%),
      while PHA-stimulated lymphocytes occupied an intermediate position between the
      other two cell types (three or four signals per allele, 15%). The data show that
      the in situ resolution of Ig C gamma genes varies throughout the cell cycle and
      is influenced by the transcriptional activity of the locus. The variability of
      the resolution patterns observed appears to reflect different levels of chromatin
      packaging, which in turn are likely to influence the probe accessibility to its
      target. These observations are relevant for the interpretation of data from
      interphase cytogenetics analysis of independent, but closely spaced, DNA
      segments.

PMID- 8530005
TI  - Asynchronous DNA replication between 15q11.2q12 homologs: cytogenetic evidence
      for maternal imprinting and delayed replication.
AB  - DNA replication kinetics of Prader-Willi/Angelman syndrome region of 15q11.2q12
      was studied without synchronization in five human amniotic cell and five skin
      fibroblast strains with a marker 15 chromosome, i.e., 15p+ or der(15), as
      cytological marker to distinguish between the two homologs. BrdU-33258 Hoechst
      Giemsa techniques were used to analyze and compare the late replication patterns
      in the 15q11.2q12 region between the homologs. Asynchronous replication between
      the homologs was observed in both amniocytes and fibroblasts. From cells of a
      marker 15 of known parental origin, the paternal 15q11.2q12 replicated earlier
      than that of the maternal 15 in 92%-95% of asynchronous metaphases. The remaining
      5%-8% of asynchronous metaphases displayed maternal early/paternal late
      replication. This mosaic pattern of replication in the 15q11.2q12 region may be
      due to methylation mosaicism of genomic imprinting or a relative lack of self
      control of replication. These results provide cytogenetic evidence of maternal
      imprinting and delayed replication in the 15q11.2q12 region.

PMID- 8530004
TI  - DNA, FISH and complementation studies in ICF syndrome: DNA hypomethylation of
      repetitive and single copy loci and evidence for a trans acting factor.
AB  - ICF syndrome (ICFS) is a rare immunodeficiency disorder characterized by
      instability of the pericentromeric heterochromatin predominantly of chromosomes 1
      and 16. DNA methylation studies in two unrelated ICFS patients provide further
      evidence for a marked hypomethylation of satellite 2 DNA. The ICFS-specific
      disturbances of chromatin structure take place within the satellite 2 DNA
      regions, as demonstrated by fluorescence in situ hybridization analysis.
      Moreover, methylation studies of genomic imprinted loci D15S63, D15S9, and H19
      have revealed hypomethylation to different degrees in both patients; this
      provides evidence for hypomethylation at autosomal single copy loci in ICFS. Cell
      fusion experiments have revealed a distinct reduction of chromosomal
      abnormalities in ICFS cells after fusion with normal cells, suggesting that the
      abnormalities are caused by the loss of function of an as yet unknown trans
      acting factor. Although it is now clear that wide-spread DNA hypomethylation is a
      characteristic feature of ICFS, neither the cause and mechanism of
      hypomethylation nor their relationship to the clinical symptoms is known. We
      speculate that a phenotypic effect might result from tissue-dependent abnormal
      gene expression and/or from a possible structural disturbance of DNA domains,
      which, with respect to the immunodeficiency, partially prevents the normal
      somatic recombinations in immunologically active cells.

PMID- 8530006
TI  - Direct molecular analysis of the fragile X syndrome in a sample of Egyptian and
      German patients using non-radioactive PCR and Southern blot followed by
      chemiluminescent detection.
AB  - Molecular genetic analysis of individuals from 6 Egyptian and 33 German families
      with fragile X syndrome and 240 further patients with mental retardation was
      performed applying a completely non-radioactive system. The aim of our study was
      the development of a non-radioactive detection method and its implementation in
      molecular diagnosis of the fragile X syndrome. Furthermore, we wanted to assess
      differences in the mutation sizes between Egyptian and German patients and
      between Egyptian and German carriers of a premutation. Using non-radioactive
      polymerase chain reaction (PCR), agarose gel electrophoresis and blotting of the
      PCR products, followed by hybridisation with a digoxigenin-labelled
      oligonucleotide probe (CGG)5 and chemiluminescent detection, we identified the
      fragile X full mutation (amplification of a CGG repeat in the FMR-1 gene ranging
      from several hundred to several thousand repeat units) in all patients. We
      observed no differences in the length of the CGG repeat between the Egyptian and
      German patients and carriers, respectively. However, in one prenatal diagnosis,
      we detected only one normal sized allele in a female fetus using the PCR-agarose
      assay, whereas Southern blot analysis with the digoxigenin labelled probe StB
      12.3 revealed presence of a full mutation. Our newly established nonradioactive
      genomic blotting method is based on the conventional radioactive Southern blot
      analysis. Labelling of the probe StB 12.3 with digoxigenin via PCR allowed the
      detection of normal, premutated and fully mutated alleles. For exact sizing of
      small premutated or large normal alleles, we separated digoxigenin labelled PCR
      products through denaturing polyacrylamide gelelectrophoresis (PAGE) and
      transfered them to a nylon membrane using a gel dryer. The blotted PCR-fragments
      can easily be detected with alkaline phosphate-labelled anti-digoxigenin
      antibody. The number of trinucleotide repeat units can be determined by scoring
      the detected bands against a digoxigenated M13 sequencing ladder. Our newly
      developed digoxigenin/chemiluminescence approach using PCR and Southern blot
      analysis provides reliable results for routine detection of full fragile X
      mutations and premutations.

PMID- 8530007
TI  - A de novo satellited short arm of the Y chromosome possibly resulting from an
      unstable translocation.
AB  - A satellited long arm of the Y chromosome (Yqs) is considered a normal variation,
      whereas the presence of a satellite on the short arm of the Y (Yps) has never
      been described in the literature. A Yps chromosome could be clinically
      significant if the translocation resulting in Yps has relocated the testis
      determining gene, SRY, to another chromosome. A carrier of such a translocation
      would therefore be at increased risk for having XX male and XY female offspring.
      Here we describe the first reported case of de novo Yps present in a
      phenotypically normal male. This Yps chromosome was positive for C-banding and
      nucleolus organizer region (NOR) staining and showed a hybridization signal for
      the beta-satellite sequence. Fluorescence in situ hybridization (FISH) analysis
      indicated that SRY was retained on the Yps and the translocation breakpoint on
      Yps was distal to the pseudoautosomal region. At prenatal diagnosis, a normal
      appearing Y chromosome was found in his son, and thus the satellite on Yps was
      lost during meiotic Xp-Yp pairing. This Yps chromosome was likely the product of
      an "unstable" translocation.

PMID- 8530008
TI  - A sublocus of the multicopy microsatellite marker CMS1 maps proximal to spinal
      muscular atrophy (SMA) as shown by recombinant analysis.
AB  - The critical region containing the spinal muscular atrophy (SMA) gene is flanked
      by the 5q11-q13 markers, D5S435 and D5S557, as determined by linkage analysis.
      Here we present the results of an analysis of a Dutch SMA family with the
      multicopy microsatellite marker CMS1. A crossover is revealed in the critical SMA
      region. We conclude that at least one of the CMS1 subloci maps proximal to the
      SMA gene. This reduces the minimal SMA region from approximately 1.4 Mb to 600
      700 kb.

PMID- 8530009
TI  - Refined mapping of the psoriasin gene S100A7 to chromosome 1cen-q21.
AB  - Psoriasin is a low molecular weight protein of the S100 family, which is highly
      upregulated in psoriatic epidermis, and whose function is related to skin
      inflammatory responses. We have applied a cDNA probe from the corresponding
      psoriasin gene S100A7 in a refined localisation analysis. S100A7 was mapped
      physically by human/rodent somatic cell hybrid analysis, and more precisely
      genetically by multilocus linkage analysis of 40 CEPH (Centre d'Etude du
      Polymorphisme Humain) families. The resulting 12-point linkage map was supported
      by odds of at least 1000:1, where S100A7 could be placed with a multipoint
      lodscore of 27.4 in an approximately 7-cM interval. The order of the 12 loci was
      as follows (with the best estimates of recombination frequencies given in
      between): AMY2B-0.091-D1S73(0.039)-D1S11(-0.053)-D1S189(-0 .017)-D1S1252 (-0.017)
      D1S13(-0.078)-D1Z5(-0.051)-S100A7(-0.022)- MUC1(-0.026)-SPTA1 (-0.066)-ATP1A2(
      0.014)-APOA2. Furthermore, from this map S100A7 could be assigned to the regional
      position of chromosome 1cen-q21. The linkage information presented should be of
      great value in association and linkage studies of diseases where psoriasin, or
      some of the several other very closely linked and functionally related genes, are
      seen as candidate genes, e.g. in psoriasis.

PMID- 8530010
TI  - Association of apolipoprotein E but not B with Alzheimer's disease.
AB  - In our studies apolipoprotein E4 (APOE4) is associated with both early- and late
      onset Alzheimer's disease. Alzheimer's patients from West Texas were screened for
      the APOE4 allele, which was found at frequencies of 0.43 and 0.59 in familial
      late- and early-onset cases. Sporadic cases had lower frequencies, but they still
      were 2-4 times higher than control spouses. To determine whether the APOE
      association may be a risk factor for coronary disease as well, we examined two
      APOB gene restriction sites that have previously been found to be associated with
      coronary artery disease, especially myocardial infarctions. The APOB alleles were
      found at similar frequencies in Alzheimer's patients and control spouses.

PMID- 8530011
TI  - A nonsense mutation in the cytochrome P450 CYP2D6 gene identified in a Caucasian
      with an enzyme deficiency.
AB  - A novel mutation that generates a stop codon in the third exon of the gene
      encoding the cytochrome P-450 CYP2D6 was identified in a Caucasian having a
      deficiency of the isozyme, by means of single strand conformation polymorphism
      analysis of DNA fragments amplified by the polymerase chain reaction, followed by
      selective sequencing.

PMID- 8530012
TI  - Familial hemiplegic migraine locus on 19p13 is involved in the common forms of
      migraine with and without aura.
AB  - Migraine is a common neurological disease of two main types: migraine with aura
      and migraine without aura. Familial clustering suggests that genetic factors are
      involved in the etiology of migraine. Recently, a gene for familial hemiplegic
      migraine, a rare autosomal dominant subtype of migraine with aura, was mapped to
      chromosome 19p13. We tested the involvement of this chromosomal region in 28
      unrelated families with the common forms of migraine with and without aura, by
      following the transmission of the highly informative marker D19S394. Sib-pair
      analysis showed that affected sibs shared the same marker allele more frequently
      than expected by chance. Our findings thus also suggest the involvement of a gene
      on 19p13 in the etiology of the common forms of migraine.

PMID- 8530013
TI  - Protein-tyrosine phosphatase SH-PTP2 (PTPN11) is localized to 12q24.1-24.3.
AB  - A 2.1-kb cDNA probe encoding the human SH2-domain containing protein-tyrosine
      phosphatase SH-PTP2 (PTPN11) was hybridized to human metaphase chromosomes in
      three independent experiments. In each instance, hybridization was maximal to
      chromosome 12q24.1-q24.3. The presence of SH-PTP2 cDNA crosshybridizing sequences
      located on a number of other chromosomes suggested that SH-PTP2-related genes or
      pseudogenes are present in the human genome.

PMID- 8530014
TI  - Human cDNA encoding the muscle isoform of the phosphorylase kinase gamma subunit
      (PHKG1).
AB  - Muscle glycogenosis caused by phosphorylase kinase (Phk) deficiency may lead to
      exercise intolerance, weakness and musculatur atrophy. The gene encoding the
      muscle isoform of the Phk gamma subunit (gamma M) is one of the candidate genes
      in which mutations responsible for this condition should be sought. Here, we
      report the cDNA sequence and the predicted primary structure of the human gamma M
      subunit.

PMID- 8530015
TI  - Single-cell PCR performed with neurofibroma Schwann cells reveals the presence of
      both alleles of the neurofibromatosis type 1 (NF1) gene.
AB  - It is commonly held that Schwann cells (SC) are the progenitor cells of benign
      neurofibromas. To test for loss of heterozygosity (LOH) at the neurofibromatosis
      1 (NF1) gene locus, three intragenic polymorphic markers were analyzed after
      polymerase chain reaction amplification, starting from 98 single SC isolated from
      primary cultures of neurofibromas, of five informative NF1 patients. The patterns
      obtained did not provide evidence for LOH at the NF1 gene. LOH by nondisjunction,
      large deletions, or somatic recombination in SC seems not to be the mechanism of
      generation of neurofibromas.

PMID- 8530016
TI  - Huntington's disease in a Sudanese family from Khartoum.
AB  - Typical Huntington's disease (HD) was studied in a 40-year-old Sudanese man from
      Khartoum. He had 51 CAG repeats in the Huntington's gene. It is suspected that
      his mother and his 16-year-old son (both deceased) were also affected. Up to now,
      there had only been anecdotal evidence of HD in the Sudanese.

PMID- 8530017
TI  - Lack of a BglII site at the 5' region of the PGK 1 locus: a new variant
      discovered in two Chibchan Amerindian groups from Costa Rica.
AB  - A new 3.8-kb allele at the 5' region of the PGK 1 locus detected by the probe
      pSPT/PGK is reported. This variant was discovered in the Cabecar and Guaymi, two
      Chibchan Amerindian groups of Costa Rica. So far, a polymorphism that consists of
      an EcoRI/BglI (1.3-kb) variable site within an EcoRI/BglII (1.7-kb) fragment when
      DNA is simultaneously digested with EcoRI, BglI and BglII is known to occur in
      black and Caucasian populations. These two alleles were also found in the
      Amerindians tested. The newly described band is due to the lack of the BglII site
      situated 1.7 kb downstream from the EcoRI site and to the cleavage of another
      BglII site 2.1 kb downstream from the lacking one. This variant might be
      restricted to some Amerindian groups and perhaps also to Asiatic populations.
      Thus, it could be a useful marker in evolutive studies and for forensic
      applications. Moreover, the presence of a third allele in populations with
      Amerindian ancestry can increase the heterozygosity of the region disclosed by
      the pSPT/PGK probe, thus improving its application in issues dealing with X
      chromosome activation ratios in females.

PMID- 8530018
TI  - Genomic organization of the human T-cell receptor variable alpha (TCRAV) gene
      cluster.
AB  - A long-range physical map of the human T-cell receptor variable alpha (TCRAV)
      locus was produced using 23 V alpha subgroup-specific probes. Linkage
      disequilibrium across the locus was also studied using polymorphic TCRAV markers.
      Pulsed-field gel electrophoresis was used to map V alpha gene segments onto one
      SfiI fragment of 500 kb and two of 200 kb using DNA from peripheral blood
      neutrophils. PCR and conventional Southern techniques on Jurkat, CEM, and H9 T
      cell lines were used to establish the 5' to 3' order of the gene segments and the
      relative positions of V alpha gene segments on the SfiI fragments. The linkage
      disequilibrium study used single-stranded conformation polymorphism analysis to
      genotype 100 normal caucasoid subjects for TCRAV5S1, V6S1, V8S1, V17S1, and V21S1
      polymorphisms. Strong linkage disequilibrium was detected between V5S1 and V8S1,
      in concordance with the physical map. This new information will be useful for
      future studies of genetic variation at the TCRAV locus, its role in the shaping
      of the TCR repertoire, and its possible contribution to autoimmune diseases.

PMID- 8530019
TI  - A 37-marker PCR-based genetic linkage map of human chromosome 9: observations on
      mutations and positive interference.
AB  - Refinement of an "index" marker genetic linkage map of human chromosome 9 using
      the CEPH reference pedigrees has been achieved through the addition of 11 markers
      to the previous map of 26 markers. Five of the 11 markers added to the map are
      new markers of the GATA repeat type, 1 is a complex repeat, and the remaining 5
      as well as the original 26 markers are all GT/CA repeats. Twelve definite and
      five probable mutations were detected in this analysis and were more common for
      the GATA repeats than the GT/CA repeats. Strong evidence for positive
      interference was seen over the length of the chromosome, but there were
      significantly more double recombination events in the pericentromeric region than
      elsewhere, suggesting that interference is less strong in that region.

PMID- 8530020
TI  - Construction of 110 cosmid markers and a 4.5-Mb YAC contig on human chromosome
      8p12-q11.
AB  - Microcell hybrids containing various regions of human chromosome 8 were formed by
      microcell-mediated transfer of neo-tagged chromosome 8 into the cells derived
      from severe combined immunodeficiency (SCID) mouse. Thus, 110 cosmid markers were
      isolated from SV40-transformed SCID fibroblast cell line (SCVA) containing a p12
      q11.1 region of human chromosome 8 and were assigned to eight regions in 8p12
      q11.1, using a microcell-hybrid panel. For positional cloning of a human gene
      that restores the DNA-repair defect in a mouse with SCID on 8p11.1-q11.1 (SCID
      region), we constructed a yeast artificial chromosome (YAC) contig of about 4.5
      Mb. Overlapping YACs were further aligned by restriction mapping, using rare
      cutting restriction endonucleases. The cosmids and YAC contig should facilitate
      isolation of the SCID gene and other genes, such as the Werner syndrome
      responsible gene in or near this region.

PMID- 8530021
TI  - Cloning and sequence analysis of the mouse smooth muscle gamma-enteric actin
      gene.
AB  - Actin represents one of the most highly conserved families of proteins in
      evolution. The work presented here describes the molecular characterization of
      the mouse smooth muscle (enteric) gamma-actin gene (SMGA). It represents the
      largest isoactin gene characterized to date, measuring over 23,000 bp from the
      transcription start site to the polyadenylation signal. The gene is divided into
      nine exons and encodes a mature actin protein of 374 amino acids. Putative
      regulatory elements are noted as well as regions of the gene that have the
      potential to form non-B DNA conformations that may influence gene expression.

PMID- 8530022
TI  - RNA expression and chromosomal location of the mouse long-chain acyl-CoA
      dehydrogenase gene.
AB  - The cDNA for mouse long-chain acyl-CoA dehydrogenase (Acadl, gene symbol; LCAD,
      enzyme) was cloned and characterized. The cDNA was obtained by library screening
      and reverse transcription-polymerase chain reaction (RT-PCR). The deduced amino
      acid sequence showed a high degree of homology to both the rat and the human LCAD
      sequence. Northern analysis of multiple tissues using the mouse Acadl cDNA as a
      probe showed two bands in all tissues examined. We found a total of three
      distinct mRNAs for Acadl. These three mRNAs were encoded by a single gene that we
      mapped to mouse chromosome 1. The three transcripts differed in the 3'
      untranslated region due to use of alternative polyadenylation sites. Quantitative
      evaluation of a multitissue Northern blot showed a varied ratio of the larger
      transcript as compared with the smaller transcripts.

PMID- 8530023
TI  - Sequences promoting the transcription of the human XA gene overlapping P450c21A
      correctly predict the presence of a novel, adrenal-specific, truncated form of
      tenascin-X.
AB  - A compact region in the human class III major histocompatibility locus contains
      the human genes for the fourth component of human complement (C4) and steroid 21
      hydroxylase (P450c21) in one transcriptional orientation, while the gene for the
      extracellular matrix protein tenascin-X (TN-X) overlaps the last exon of P450c21
      on the opposite strand of DNA in the opposite transcriptional orientation. This
      complex locus is duplicated into A and B loci, so that the organization is 5'-C4A
      21A-XA-C4B-21B-XB-3'. Although this duplication event truncated the 65-kb X(B)
      gene to a 4.5-kb XA gene, the XA gene is transcriptionally active in the adrenal
      cortex. To examine the basis of the tissue-specific expression of XA and C4B, we
      cloned the 1763-bp region that lies between the cap sites for XA and C4B and
      analyzed its promoter activity in both the XA and the C4 orientations. Powerful,
      liver-specific sequences lie within the first 75 to 138 bp from the C4B cap site,
      and weaker elements lie within 128 bp of the XA cap site that function in both
      liver and adrenal cells. Because these 128 bp upstream from the XA cap site are
      perfectly preserved in the XB gene encoding TN-X, we sought to determine whether
      a transcript similar to XA arises within the XB gene. RNase protection assays,
      cDNA cloning, and RT/PCR show that adrenal cells contain a novel transcript,
      termed short XB (XB-S), which has the same open reading frame as TN-X.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8530024
TI  - Murine chromosomal location of five bHLH-Zip transcription factor genes.
AB  - The genes for the bHLH-Zip transcription factors Tfap4, Mxi1, Tcfeb, Usf1, and
      Usf2 have been mapped in mouse by interspecific backcross analysis. Mxi1, Usf1,
      and Usf2 have been mapped previously by in situ hybridization, but their
      positions on the meiotic linkage map had not been determined. The other two genes
      have not previously been mapped in mouse. These transcription factors belong to a
      growing family of transcriptional regulators, some of which are known to form a
      complex network of interacting proteins that control cell proliferation and
      apoptosis. As expected, based on mapping studies of other bHLH-Zip genes, these
      loci were well distributed among mouse chromosomes. In addition, some of the
      probes used in this study detected multiple, independently segregating loci,
      suggesting the possible existence of additional family members or species
      specific pseudogenes.

PMID- 8530025
TI  - Characterization of human lymphoid cell lines GM9947 and GM9948 as intra- and
      interlaboratory reference standards for DNA typing.
AB  - The incorporation of reference DNA is crucial to the validation of any DNA typing
      protocol. Currently, reference DNA standards are restricted to molecular size DNA
      ladders and/or tumor cell line DNA. Either of these, however, presents some
      limitations. We have rigorously characterized two Epstein-Barr virus (EBV)
      immortalized human lymphoid cell lines--GM9947 (female) and GM9948 (male)--to
      determine their suitability as alternative in-line standards for three widely
      employed allele profiling strategies. Twenty-one highly polymorphic VNTR-based
      allelic systems (7 RFLPs, 2 AmpFLPs, and 12 STRs) distributed over 12 chromosomes
      were scrutinized along with 3 gender-based discriminatory systems. The genetic
      stability of each locus was confirmed over a period of 225 in vitro population
      doublings. Allele size estimates and degree of informativeness for each of the 21
      VNTR systems were compiled. The reproducibility of allele scoring by traditional
      RFLP analyses, using both cell lines as reference standards, was also verified by
      an interlaboratory validation study involving 13 analysts from two geographically
      distinct forensic laboratories. Taken together, our data indicate that GM9947 and
      GM9948 genomic DNAs could be adopted as reliable reference standards for DNA
      typing.

PMID- 8530026
TI  - Structure and mapping of the human thymopoietin (TMPO) gene and relationship of
      human TMPO beta to rat lamin-associated polypeptide 2.
AB  - Thymopoietins (TMPOs, previously abbreviated TPs) alpha (75 kDa), beta (51 kDa),
      and gamma (39 kDa) are related nuclear proteins expressed in many or all tissues.
      TMPO alpha is present diffusely throughout the nucleus, while TMPOs beta and
      gamma are localized to the nuclear membrane. Here we report the cloning and
      analysis of a single TMPO gene encoding TMPOs alpha, beta, and gamma, which are
      produced by alternative mRNA splicing, as previously inferred from cDNA
      sequences. The eight exons of the TMPO gene are spread over approximately 35 kb.
      Exon 4, which is spliced into TMPO alpha mRNA, contains sequences that encode a
      putative basic nuclear localization motif. Exon 8, which is spliced into TMPO
      beta and gamma mRNAs, encodes a hydrophobic putative membrane-spanning domain
      that is thought to target TMPOs beta and gamma to the nuclear membrane. TMPO beta
      appears to be the human homologue of the recently described rat protein LAP2
      (lamina-associated polypeptide 2), which is thought to play an important role in
      the regulation of nuclear architecture by binding lamin B1 and chromosomes in a
      manner regulated by phosphorylation during mitosis (K. Furukawa and L. Gerace, La
      Jolla, pers. comm., 22 Nov. 1994). The human TMPO gene maps to chromosome band
      12q22.

PMID- 8530027
TI  - Isolation, characterization, and precise physical localization of human CDX1, a
      caudal-type homeobox gene.
AB  - The human CDX1 gene has been isolated from a small intestine cDNA library using a
      murine Cdx1 cDNA probe. The nucleotide sequence of CDX1 is 81% identical to
      murine Cdx1 and predicts a 265-amino-acid protein with 85% identity to the mouse
      protein (98% identity, including conservative amino acid changes). The CDX1 locus
      has been mapped to a cosmid contig from chromosome 5q31-q33, placing CDX1
      approximately 100 kb distal to CSFIR. Expression of CDX1 in adults appears to be
      limited to the intestine and colon by Northern analysis, suggesting a possible
      role in the terminal differentiation of the intestine. Further analysis of CDX1
      should elucidate the function of caudal-type homeobox genes in human development.

PMID- 8530028
TI  - Retinal degeneration slow (rds) in mouse results from simple insertion of a t
      haplotype-specific element into protein-coding exon II.
AB  - Retinal degeneration slow (rds) is a semidominant mutation of mice that causes
      dysplasia and degeneration of rod and cone photoreceptors. Mutations in RDS, the
      human ortholog of the rds gene, are responsible for several inherited retinal
      dystrophies including a subset of retinitis pigmentosa. The normal rds locus
      encodes rds/peripherin, an integral membrane glycoprotein present in outer
      segment discs. Genomic libraries from wildtype and rds/rds mice were screened
      with an rds cDNA, and phage lambda clones that span the normal and mutant loci
      were mapped. We show that in mice, rds is caused by the insertion into exon II of
      a 9.2-kb repetitive genomic element that is very similar to the t haplotype
      specific element in the H-2 complex. The entire element is included in the RNA
      products of the mutant locus. We present evidence that rds in mice represents a
      null allele.

PMID- 8530029
TI  - Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and
      chromosomal localization.
AB  - We have previously identified a novel rat neuronal member of the pentraxin family
      (neuronal pentraxin) that may mediate the uptake of synaptic material and the
      presynaptic snake venom toxin, taipoxin. Here we report human cDNA and genomic
      sequences of a second neuronal pentraxin. This pentraxin, which we propose to
      name neuronal pentraxin II (NPII; gene symbol NPTX2), shows 54% amino acid
      identity to rat neuronal pentraxin (NPI) with 69% identity over the carboxyl
      terminal half of NPI and is 88% identical to a newly identified sperm acrosomal
      pentraxin p50/apexin. Northern blot analysis reveals that NPII message is present
      in brain, testis, pancreas, liver, heart, and skeletal muscle, so, unlike NPI,
      NPII is not exclusively localized to neurons. Like NPI, NPII has potential N
      linked glycosylation sites. The human NPII gene is 11 kb in length, contains four
      introns, and is localized to chromosome 7q21.3-q22.1. These data demonstrate the
      existence of a family of pentraxin proteins that are expressed in the brain and
      other tissues and that may play important roles in the uptake of extracellular
      material.

PMID- 8530030
TI  - Complex genetic organization of junB: multiple blocks of flanking evolutionarily
      conserved sequence at the murine and human junB loci.
AB  - A comparison of the murine and human junB loci reveals nine regions of distal 5'-
      and 3'-flanking DNA that exhibit greater than 72% sequence identity. A large
      fraction (over 50%) of the junB locus is contained in these flanking
      evolutionarily conserved sequences (FECS), which may be required for effecting
      the proper transcriptional regulation of this gene. Comparative sequence analyses
      involving kilobases of distal flanking DNAs have been performed for only a small
      number of vertebrate genes. The available data and the results presented here
      suggest that FECS may emerge as common yet important functional components of
      genes, a hypothesis with significant implications for characterizing genes
      involved in human disease.

PMID- 8530031
TI  - Characterization and chromosomal localization of ELANH2, the gene encoding human
      monocyte/neutrophil elastase inhibitor.
AB  - Human monocyte/neutrophil elastase inhibitor (HEI) is a protease inhibitor of the
      serpin superfamily that rapidly inactivates neutrophil elastase, proteinase-3,
      and possibly cathepsin-G in vitro and, by regulating these potent proteases, is
      thought to prevent tissue damage at inflammatory sites. The HEI gene (ELANH2) was
      characterized by amplifying intron regions using cDNA-specific primers. Intron
      positions of ELANH2 were found to be homologous to intron positions in the genes
      for the serpin molecules chicken ovalbumin and human plasminogen activator
      inhibitor-2 (PLANH2). Because serpin superfamily genes in general have widely
      different organizational patterns, the shared organization of these genes
      strengthens the evidence that they form a subgroup or family, the "ovalbumin
      related serpin" ("Ov-serpin") family. By amplifying DNA of a somatic cell hybrid
      panel, ELANH2 was unambiguously localized to chromosome 6. The use of a panel of
      radiation and somatic cell hybrids specific for chromosome 6 refined the
      localization of ELANH2 to the short arm telomeric of D6S89, F13A, and D6S202 at
      6p24-pter. Another Ov-serpin gene PI6 (placental thrombin inhibitor) was
      colocalized to the same region, thus defining an Ov-serpin locus on chromosome 6
      in addition to the previously defined PLANH2-containing Ov-serpin locus on
      chromosome 18.

PMID- 8530032
TI  - The human myelin oligodendrocyte glycoprotein (MOG) gene: complete nucleotide
      sequence and structural characterization.
AB  - Human myelin oligodendrocyte glycoprotein (MOG), a myelin component of the
      central nervous system, is a candidate target antigen for autoimmune-mediated
      demyelination. We have isolated and sequenced part of a cosmid clone that
      contains the entire human MOG gene. The primary nuclear transcript, extending
      from the putative start of transcription to the site of poly(A) addition, is
      15,561 nucleotides in length. The human MOG gene contains 8 exons, separated by 7
      introns; canonical intron/exon boundary sites are observed at each junction. The
      introns vary in size from 242 to 6484 bp and contain numerous repetitive DNA
      elements, including 14 Alu sequences within 3 introns. Another Alu element is
      located in the 3'-untranslated region of the gene. Alu sequences were classified
      with respect to subfamily assignment. Seven hundred sixty-three nucleotides 5' of
      the transcription start and 1214 nucleotides 3' of the poly(A) addition sites
      were also sequenced. The 5'-flanking region revealed the presence of several
      consensus sequences that could be relevant in the transcription of the MOG gene,
      in particular binding sites in common with other myelin gene promoters. Two
      polymorphic intragenic dinucleotide (CA)n and tetranucleotide (TAAA)n repeats
      were identified and may provide genetic marker tools for association and linkage
      studies.

PMID- 8530033
TI  - Linkage mapping in Papio baboons: conservation of a syntenic group of six markers
      on human chromosome 1.
AB  - We have established multipoint genetic linkage among six loci in baboons (Papio
      hamadryas). Published PCR primers designed to amplify five human microsatellite
      loci were used to amplify homologous loci in 229 pedigreed baboons. Southern
      blotting was used to type two RFLPs in a functional gene (anti-thrombin III) in a
      subset of those animals. All six loci are known to map to human chromosome 1q, a
      region of the genome predicted by karyotype studies to be conserved in baboons.
      Pairwise recombination frequencies and lod scores indicate that the six loci are
      also linked in baboons. Recombination distances among the loci are similar to
      those reported for humans. Like humans, the baboons exhibit higher rates of
      recombination in females than in males. This study demonstrates that (1)
      microsatellite loci first described and characterized in the human genome can be
      effectively used for genetic linkage mapping in non-human primates, (2) a group
      of genetic loci known to be linked on human chromosome 1q are also linked in the
      baboon genome, and (3) sex differences in recombination frequencies among loci on
      human chromosome 1q are also observed in the genome of this Old World monkey.
      This constitutes the first reported multipoint linkage map in any nonhuman
      primate.

PMID- 8530034
TI  - Cloning and mapping of a human gene (TBX2) sharing a highly conserved protein
      motif with the Drosophila omb gene.
AB  - We have identified and cloned a human gene (TBX2) that exhibits strong sequence
      homology within a putative DNA binding domain to the drosophila optomotor-blind
      (omb) gene and lesser homology to the DNA binding domain of the murine brachyury
      or T gene. Unlike omb, which is expressed in neural tissue, or T, which is not
      expressed in adult animals, TBX2 is expressed primarily in adult in kidney, lung,
      and placenta as multiple transcripts of between approximately 2 and 4 kb. At
      least part of this transcript heterogeneity appears to be due to alternative
      polyadenylation. This is the first reported human member of a new family of
      highly evolutionarily conserved DNA binding proteins, the Tbx or T-box proteins.
      The human gene has been mapped by somatic cell hybrid mapping and chromosomal in
      situ hybridization to chromosome 17q23, a region frequently altered in ovarian
      carcinomas.

PMID- 8530036
TI  - Chromosomal loci of 50 human keratinocyte cDNAs assigned by fluorescence in situ
      hybridization.
AB  - The chromosomal loci of expressed genes provide useful information for a
      candidate gene approach to the genes responsible for genetic diseases. A large
      set of randomly isolated cDNAs catalogued by partial sequencing can serve as a
      resource for accessing and isolating these disease genes. Using fluorescence in
      situ hybridization, we examined the chromosomal loci of 217 human keratinocyte
      derived cDNAs, with independent novel sequence tags at the 3' end region. Among
      them, we determined the loci of 50 cDNAs. Single-pass sequencing of these from
      the 5' ends indicated that 39 cDNAs still can be produced for new genes. These
      cDNAs with identified chromosomal loci are powerful tools that can be used to
      help elucidate the genes responsible for hereditary skin disorders.

PMID- 8530035
TI  - Structure and chromosomal localization of the human gene of the phosphotyrosyl
      phosphatase activator (PTPA) of protein phosphatase 2A.
AB  - The PTPA gene encodes a specific phosphotyrosyl phosphatase activator of the
      dimeric form of protein phosphatase 2A. PTPA, cloned from human genomic
      libraries, is encoded by one single-copy gene, composed of 10 exons and 9 introns
      with a total length of about 60 kb. The transcription start site was determined,
      and the 5' flanking sequence was analyzed for its potential as a promotor. This
      region lacks a TATA sequence in the appropriate position relative to the
      transcription start, is very GC-rich, and contains upstream of the transcription
      start four Sp1 sites, a feature common to many TATA-less promotors. Based on the
      homology with DNA binding consensus sequences of transcription factors, we
      identified in this promotor region several putative DNA binding sites for
      transcription factors, such as NF-kappa B, Myb, Ets-1, Myc, and ATF. Transfection
      experiments with a construct containing the PTPA promotor region inserted 5' of a
      luciferase reporter gene revealed that the 5' flanking sequence of the PTPA gene
      indeed displayed promotor activity that seems to be cell-line dependent. By
      fluorescence in situ hybridization and G-banding, the PTPA gene was localized to
      the 9q34 region. The PTPA gene is positioned centromeric of c-abl in a region
      embracing several genes implicated in oncogenesis.

PMID- 8530037
TI  - Mapping of the 75-kDa inositol polyphosphate-5-phosphatase (Inpp5b) to distal
      mouse chromosome 4 and its exclusion as a candidate gene for dysgenetic lens.
AB  - We have determined the chromosomal localization of the murine gene encoding a 75
      kDa inositol polyphosphate-5-phosphatase (Inpp5b). Using two independent
      approaches, fluorescence in situ hybridization and interspecific backcross
      analysis, we show that Inpp5b maps to distal mouse Chromosome 4. This map
      position is within the conserved linkage group corresponding to the short arm of
      human Chromosome 1, where the human homologue, INPP5B, has been shown to map
      previously. The position of Inpp5b on mouse Chromosome 4 is in the vicinity of
      the mouse developmental mutation dysgenetic lens (dyl). However, using a genetic
      approach, we show that Inpp5b maps distal to dyl on mouse Chromosome 4.

PMID- 8530038
TI  - Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the
      defect in CMT4A.
AB  - We have previously localized one form of the autosomal recessive Charcot-Marie
      Tooth disease type 4 (CMT4A) to a 5-cM region of chromosome 8q13-q21. We now
      report the formation of a 7-Mb YAC contig spanning the region. This contig was
      used to map nine additional microsatellites and six STSs to this region, and
      subsequent haplotype analysis has narrowed the CMT4A flanking interval to less
      than 1 cM. In addition, using SSCP and our physical map, we have demonstrated
      that the myelin protein PMP-2, mapped by FISH to this region, is not the defect
      in CMT4A.

PMID- 8530039
TI  - Identification and characterization of a new human gene (APOC4) in the
      apolipoprotein E, C-I, and C-II gene locus.
AB  - We have identified and characterized a previously unreported human gene that is
      found within the apolipoprotein (apo) E/C-I/C-II gene locus. On the basis of its
      location and its properties, this new gene has been designated APOC4. Nucleotide
      sequence analysis of genomic DNA and liver cDNA clones revealed a 3.3-kb gene
      consisting of three exons and two introns. Its 3' terminus lies 555 bp upstream
      of APOC2, giving both genes the same transcriptional orientation. The promoter of
      the APOC4 gene lacks a typical TATA box, consistent with an apparent
      heterogeneity in transcription start sites. RNase protection analysis indicated
      relatively low apoC-IV mRNA levels in human liver, compared to apoC-II mRNA
      levels. The predicted apoC-IV protein sequence, comprising 127 amino acid
      residues, contains a putative 25-residue signal peptide and two potential
      amphipathic alpha-helical domains. Amino acid sequence comparisons indicate a
      limited homology between apoC-IV and either apoC-I or apoC-II. Since its hepatic
      expression and predicted protein structure are characteristic of the other genes
      in this cluster, we propose that the APOC4 gene is a member of the apolipoprotein
      gene family.

PMID- 8530040
TI  - Identification of a novel conserved human gene, TEGT.
AB  - A novel gene, TEGT (testis enhanced gene transcript), has been identified in
      humans. It does not belong to any known gene family of vertebrates. The deduced
      amino acid sequence of the gene and a bacterial protein of unknown function show
      low but significant homology and very similar hydrophobicity profiles. Two
      different transcripts of TEGT occur, which are due to alternative usage of two
      polyadenylation sites. The presence of a nuclear targeting motif indicates that
      the gene product might localize to the nucleus. The TEGT gene maps to human
      chromosome 12q12-q13 and belongs to a syntenic group, which is conserved in
      human, mouse, and rat.

PMID- 8530041
TI  - High-resolution comparative mapping of the proximal region of the mouse X
      chromosome.
AB  - The murine homologues of the loci for McLeod syndrome (XK), Dent's disease
      (CICN5), and synaptophysin (SYP) have been mapped to the proximal region of the
      mouse X chromosome and positioned with respect to other conserved loci in this
      region using a total of 948 progeny from two separate Mus musculus x Mus spretus
      backcrosses. In the mouse, the order of loci and evolutionary breakpoints (EB)
      has been established as centromere-(DXWas70, DXHXF34h)-EB-Clcn5-(Syp, DXMit55,
      DXMit26)-Tfe3-Gata1-EB-Xk-Cybb-telomere. In the proximal region of the human X
      chromosome short arm, the position of evolutionary breakpoints with respect to
      key loci has been established as DMD-EB-XK-PFC-EB-GATA1-C1CN5-EB-DXS1272E-ALAS2-E
      B-DXF34-centromere. These data have enabled us to construct a high-resolution
      genetic map for the approximately 3-cM interval between DXWas70 and Cybb on the
      mouse X chromosome, which encompasses 10 loci. This detailed map demonstrates the
      power of high-resolution genetic mapping in the mouse as a means of determining
      locus order in a small chromosomal region and of providing an accurate framework
      for the construction of physical maps.

PMID- 8530042
TI  - A locus for cerebral cavernous malformations maps to chromosome 7q in two
      families.
AB  - Cavernous malformations (angiomas) affecting the central nervous system and
      retina can be inherited in autosomal dominant pattern (OMIM 116860). These
      vascular lesions may remain clinically silent or lead to a number of neurological
      symptoms including seizure, intracranial hemorrhage, focal neurological deficit,
      and migraine. We have mapped a gene for this disorder in two families, one of
      Italian-American origin and one of Mexican-American origin, to markers on
      proximal 7q, with a combined maximum lod score of 3.92 (theta of zero) with
      marker D7S479. Haplotype analysis of these families places the locus between
      markers D7S502 proximally and D7S515 distally, an interval of approximately 41
      cM. The location distinguishes this disorder from an autosomal dominant vascular
      malformation syndrome where lesions are primarily cutaneous and that maps to
      9p21.

PMID- 8530043
TI  - Rapid construction of integrated maps using inner product mapping: YAC coverage
      of human chromosome 11.
AB  - Inner product mapping (IPM) has been proposed as a hybridization-based method for
      achieving low-cost, high-throughput, high-resolution radiation hybrid (RH)
      mapping of clones. Using Alu-PCR products of chromosome 11-specific clones, we
      serially hybridized a set of RHs against gridded filters of YACs having an
      average size of 350 kb. We then combined these hybridization data with
      preexisting RH map data to build an inner product map. This binning of 865 YACs
      provides the first high-resolution large-scale (> twofold redundancy) clonal
      coverage of human chromosome 11 and is the first inner product map ever
      constructed. We verified the accuracy and precision of this chromosome 11 map by
      performing a novel likelihood analysis on independent YAC hybridization data.
      These results establish that IPM is a highly rapid, inexpensive, accurate, and
      precise large-scale long-range mapping method, particularly when preexisting RH
      maps are available, and that IPM can replace or complement more conventional
      short-range mapping methods. IPM may enable the rapid construction of sequence
      ready maps and the binning of expressed sequences.

PMID- 8530044
TI  - A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24.
AB  - The CYP2C gene cluster on chromosome 10q24 encodes the P450IIC enzymes, members
      of the cytochrome P450 monooxygenase superfamily. The P450-IIC enzymes are
      required for the metabolism of a number of foreign compounds, including the drugs
      mephenytoin and tolbutamide, and are also thought to be involved in the
      metabolism of endogenous steroid hormones. Several different CYP2C cDNA clones
      have been isolated; however, the exact number of genes and the genomic
      arrangement of the CYP2C cluster have remained unknown. Using a combination of
      STS and restriction mapping to characterize YAC clones, we have constructed a 2.4
      Mb physical map that incorporates the CYP2C gene cluster. The cluster spans
      approximately 500 kb on proximal 10q24 and comprises four genes arranged in the
      order CYP2C8-CYP2C9-CYP2C19-CYP2C18. The map also includes an adjacent gene, the
      serum retinol binding protein gene (RBP4). The incorporation of Genethon CA
      repeat genetic markers suggests the orientation of the loci to be Cen-RBP4
      CYP2C18-CYP2C19-CYP2C9-CYP2C8-Tel .

PMID- 8530045
TI  - Mouse chromosomal location of the CCAAT/enhancer binding proteins C/EBP beta
      (Cebpb), C/EBP delta (Cebpd), and CRP1 (Cebpe).
AB  - There are four known members of the C/EBP family of basic region-leucine zipper
      transcription factors: Cebpa, Cebpb, Cebpd, and Cebpe. Cebpa has previously been
      mapped to mouse chromosome 7. Here, we show that Cebpb maps to mouse chromosome
      2, Cebpd to chromosome 16, and Cebpe to chromosome 14. The assignment of Cebpd to
      chromosome 16 identifies a new region of homology between mouse chromosome 16 and
      human chromosome 8.

PMID- 8530046
TI  - Coding sequence and alternative splicing of the mouse alpha 1(XI) collagen gene
      (Col11a1).
AB  - Several overlapping cDNA clones corresponding to the entire coding sequence of
      the mouse alpha 1(XI) collagen gene (Col11 a1) were isolated. The conceptual
      amino acid translation indicated a high degree of sequence identity (93%) with
      the human alpha 1(XI) chain. The cloning experiments also revealed alternative
      splicing of the sequence coding for 85 residues located within the acidic region
      of the amino-globular domain of alpha 1(XI). Analysis of RNA samples from
      different embryonic tissues suggested that alternative splicing might be confined
      to tissue destined to become bone.

PMID- 8530047
TI  - Characterization of the cDNA and the gene encoding murine adenylosuccinate lyase.
AB  - Adenylosuccinate lyase catalyzes two similar reactions in the de novo purine
      biosynthetic pathway; the cleavage of succinylaminoimidazole carboxamide ribotide
      to aminoimidazole carboxamide ribotide and fumarate and the cleavage of
      adenylosuccinate to adenylate and fumarate. Adenylosuccinate lyase is also a
      participant in the purine nucleotide cycle which plays an important role in
      maintaining the AMP levels in muscle. In order to understand the
      structure/function and evolutionary relationships of the members of the fumarate
      gene family and to evaluate the possible existence of tissue specific isoforms of
      adenylosuccinate lyase, we have isolated and characterized the murine cDNA and
      gene encoding adenylosuccinate lyase. The cDNA has 94% and 87% identity to the
      human sequence at the amino acid and nucleotide levels respectively. The gene is
      about 27 kb and contains 13 exons. Comparison of the exon/intron structure of
      this gene with the argininosuccinate lyase gene did not suggest gene duplication
      or exon shuffling as a mechanism of evolution in the fumarate gene family.

PMID- 8530049
TI  - Molecular cloning and chromosomal localization of human genes encoding three
      closely related G protein-coupled receptors.
AB  - Cosmids containing human genes for three orphan G protein-coupled receptors,
      GPR12, GPR6, and GPR3, were isolated using their rat homologs as probes. Previous
      studies of the mouse and rat cDNAs have shown the receptors to be expressed
      primarily in brain but have failed to identify their ligands. The three receptor
      proteins of 334, 363, and 330 amino acids, respectively, are encoded by a single
      exon in each gene. Excluding the divergent sequences preceding the first
      transmembrane domain, they have approximately 60% amino acid identity with each
      other. Fluorescence in situ hybridization of GPR12, GPR6, and GPR3 localized
      these three genes to human chromosomal regions 13q12, 6q21, and 1p34.3-p36.1,
      respectively.

PMID- 8530048
TI  - Sialoadhesin (Sn) maps to mouse chromosome 2 and human chromosome 20 and is not
      linked to the other members of the sialoadhesin family, CD22, MAG, and CD33.
AB  - Sialoadhesin is a cell-cell interaction molecule expressed by subpopulations of
      tissue macrophages. It contains 17 immunoglobulin (Ig)-like domains and is
      structurally related to CD22, MAG, and CD33. These molecules establish a distinct
      family of sialic acid-dependent adhesion molecules, the sialoadhesin family. We
      have mapped the rodent sialoadhesin gene, Sn, to chromosome 2F-H1 by in situ
      hybridization (ISH) and shown linkage to Il1b and four other markers by backcross
      linkage analysis. We have also used ISH and a human-mouse somatic cell hybrid
      panel to localize the human sialoadhesin gene, SN, to the conserved syntenic
      region on human chromosome 20p13. This demonstrates that the sialoadhesin gene is
      not linked to the other members of the Sialoadhesin family, CD22, MAG, and CD33,
      which have been independently mapped to the distal region of mouse chromosome 7
      and to human chromosome 19q13.1-3.

PMID- 8530050
TI  - Assignment of the 49-kDa (PRIM1) and 58-kDa (PRIM2A and PRIM2B) subunit genes of
      the human DNA primase to chromosome bands 1q44 and 6p11.1-p12.
AB  - DNA primase is an essential replication protein that catalyzes the synthesis of
      oligoribonucleotide primers. DNA primase, consisting of two subunits (p49 and
      p58), plays a key role in both the initiation of DNA replication and the
      synthesis of Okazaki fragments for lagging strand synthesis. We mapped the
      locations of human chromosomes of the genes coding for both subunits [p49 (PRIM1)
      and p58 (PRIM2)] by PCR amplification using DNAs of a panel of somatic hybrids,
      to chromosomes 1 and 6, respectively. The PRIM1 gene was mapped to 1q44, and two
      PRIM2 loci (PRIM2A and PRIM2B) were detected at 6p11.1-p12 by fluorescence in
      situ hybridization using several genomic DNA probes.

PMID- 8530051
TI  - Assignment of the GLG1 gene for MGF-160, a fibroblast growth factor and E
      selectin binding membrane sialoglycoprotein of the Golgi apparatus, to chromosome
      16q22-q23 by fluorescence in situ hybridization.

PMID- 8530052
TI  - Assignment of human transforming growth factor-beta type I and type III receptor
      genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively.

PMID- 8530053
TI  - Assignment of the ets-related transcription factor E1A-F gene (ETV4) to human
      chromosome region 17q21.

PMID- 8530054
TI  - Assignment of the human membrane-type matrix metalloproteinase (MMP14) gene to
      14q11-q12 by in situ hybridization.

PMID- 8530055
TI  - Localization of the human estrogen-responsive finger protein (EEP) gene (ZNF147)
      within a YAC contig containing the myeloperoxidase (MPO) gene.

PMID- 8530056
TI  - Amphiphysin (Amph) maps to the proximal region of mouse chromosome 13.

PMID- 8530057
TI  - Localization of the synapsin II (SYN2) gene to human chromosome 3 and mouse
      chromosome 6.

PMID- 8530058
TI  - Sequence-based analysis of properdin deficiency: identification of point
      mutations in two phenotypic forms of an X-linked immunodeficiency.
AB  - Properdin deficiency is an inherited X-linked disorder causing increased
      susceptibility to meningococcal disease. Here, underlying genetic defects in the
      properdin gene were identified for the first time. Samples from individuals with
      type I deficiency, defined as complete absence of properdin in serum, and
      individuals with type II deficiency, characterized by low concentrations of
      properdin in serum, were analyzed by direct chromosome sequencing of overlapping
      PCR products. The complete gene, including 10 exons and 9 introns, covering 6460
      bases of the region Xp11, was investigated by direct solid-phase sequencing. In
      the related individuals with type I deficiency a C to T mutation in exon 5 was
      identified, which gives rise to a stop codon TGA and thus a truncated gene
      product. In addition, point mutations were found in 4 introns and a silent
      mutation in exon 10. In the properdin gene from related individuals with type II
      deficiency two point mutations were found, one in intron 3 and one in exon 4. The
      latter mutation yields a substitution of arginine to tryptophan, which may affect
      folding, secretion, and/or turnover of the protein. The genetic and biochemical
      implications of these mutations are discussed.

PMID- 8530059
TI  - Construction and characterization of a NotI linking library from human chromosome
      region 1q25-qter.
AB  - Chromosome 1q25-qter-specific NotI linking clones have been isolated from a NotI
      linking library that was constructed using DNA from MCH206.1 somatic cell hybrid
      cells. These cells contain chromosome 1q25-qter translocated to human chromosome
      Xp22 as the only human genetic material in mouse background. Sixty-eight NotI
      linking clones have been mapped by a combination of fluorescence in situ
      hybridization and R-banding to cytogenetic bands on the long arm of chromosome 1.
      The relative order of 11 NotI clones and their relation to known chromosome 1
      markers have also been determined in 1q32 and 1q41, where the genes of Van der
      Woude and Usher syndrome type IIa have been previously mapped: cen-chr1.14
      chr1.79-chr1.56-chr1.11-chr1.9 5- chr1.58 (chr1.74)-D1S70-chr1.15-chr1.82
      (chr1.143)-chr1.62-D1S81-tel. The 1q32- and 1q41-specific NotI linking clones
      were sequenced in the vicinity of the NotI site. They were analyzed in terms of
      nucleotide composition, G+C content, frequency of CpG dinucleotides, and protein
      coding potentials. Most of the 1q32-q41-specific NotI linking clones were derived
      from CpG islands. Sequences of three NotI linking clones proved to be identical
      with known genes. Six of the remaining eight had a high potential for coding
      regions and shared short homologous regions with sequences in the GenBank
      database. The NotI linking clones and the identified CpG islands will provide
      valuable resources for constructing a long-range restriction map of chromosome
      1q25-q44 and for the eventual isolation of disease genes of Van der Woude
      syndrome (1q32-q41) and Usher syndrome type IIa (1q41).

PMID- 8530060
TI  - Molecular cloning and characterization of the mouse carboxyl ester lipase gene
      and evidence for expression in the lactating mammary gland.
AB  - DNA hybridization was used to isolate a 2.04-kb cDNA encoding carboxyl ester
      lipase (CEL) from a mouse lactating mammary gland, lambda gt10 cDNA library. The
      cDNA sequence translated into a protein of 599 amino acids, including 20 amino
      acids of a putative signal peptide. Comparison of the deduced amino acid sequence
      of the mouse CEL with CEL from five other species revealed that there is a high
      degree of homology between the different species. The mouse CEL gene was also
      isolated and found to span approximately 7.2 kb and to include 11 exons. This
      organization is similar to those of the recently reported human and rat CEL
      genes. We have also analyzed expression of the CEL gene in the mammary glands
      from other species by performing a Northern blot analysis with RNA from goat and
      cow. The results show that the gene is expressed in both species.

PMID- 8530061
TI  - Molecular genetic analysis of distal mouse chromosome 6 defines gene order and
      positions of the deafwaddler and opisthotonos mutations.
AB  - Two neurological mutants deafwaddler (dfw) and opisthotonos (opt) and a cluster
      of three Shaker-like potassium (K) channel genes Kcna1, Kcna5, and Kcna6 were all
      independently mapped to distal mouse chromosome six (Chr 6). In this study,
      genetic and molecular techniques were employed to assess directly the linkage of
      the two mutants and to investigate the likelihood that a mutation in one of the
      three K channel genes may underlie dfw and/or opt. Genetic crosses testing for
      allelism showed that the dfw and opt mutations complement each other. Additional
      crosses demonstrated that the mutants are separated by a recombination distance
      of 3.1 +/- 1.8 cM. Microsatellite marker analysis of the crossover chromosomes
      recovered from the opt, dfw recombination study indicated that opt maps
      centromeric to dfw. The location of the K channel genes relative to the dfw
      mutation was determined by mapping these genes and 15 microsatellite markers in
      an intersubspecific backcross (IB) segregating for dfw [(CAST/Ei-+/+ x C3HeB/FeJ
      dfw/dfw) x C3HeB/FeJ-dfw/dfw]. Analysis of the backcross progeny positioned the
      dfw locus in the interval between the microsatellite markers D6Mit11 and D6Mit55,
      D6Mit63. The K channel cluster maps telomeric to dfw. This study establishes the
      gene order cen-opt-dfw-Rho (D6Mit44)-Kcna1, Kcna5, Kcna6 on distal mouse Chr 6
      and suggests that the neurological mutants opt and dfw affect two different
      genes, neither of which is caused by a mutation in any one of the three clustered
      K channels.

PMID- 8530062
TI  - The mouse mutation progressive motor neuronopathy (pmn) maps to chromosome 13.
AB  - Analysis of polymorphic markers segregating in both intra- and interspecific
      crosses has allowed us to map the autosomal recessive mutation progressive motor
      neuronopathy (pmn) to mouse Chr 13. Although this mutation, based on its
      histological description, was reported as a model for infantile spinal muscular
      atrophy of the Werdnig-Hoffmann type, its localization to a region that is not
      homologous with human 5q makes it unlikely to be a homologue to SMA. The presence
      of the Extra-toe (Xt) locus in proximity to pmn will help in the detection of
      affected progenies before the onset of the degenerative process.

PMID- 8530063
TI  - Alu repeats: a source for the genesis of primate microsatellites.
AB  - As a result of their abundance, relatively uniform distribution, and high degree
      of polymorphism, microsatellites and minisatellites have become valuable tools in
      genetic mapping, forensic identity testing, and population studies. In recent
      years, a number of microsatellite repeats have been found to be associated with
      Alu interspersed repeated DNA elements. The association of an Alu element with a
      microsatellite repeat could result from the integration of an Alu element within
      a preexisting microsatellite repeat. Alternatively, Alu elements could have a
      direct role in the origin of microsatellite repeats. Errors introduced during
      reverse transcription of the primary transcript derived from an Alu "master" gene
      or the accumulation of random mutations in the middle A-rich regions and
      oligo(dA)-rich tails of Alu elements after insertion and subsequent expansion and
      contraction of these sequences could result in the genesis of a microsatellite
      repeat. We have tested these hypotheses by a direct evolutionary comparison of
      the sequences of some recent Alu elements that are found only in humans and are
      absent from nonhuman primates, as well as some older Alu elements that are
      present at orthologous positions in a number of nonhuman primates. The origin of
      "young" Alu insertions, absence of sequences that resemble microsatellite repeats
      at the orthologous loci in chimpanzees, and the gradual expansion of
      microsatellite repeats in some old Alu repeats at orthologous positions within
      the genomes of a number of nonhuman primates suggest that Alu elements are a
      source for the genesis of primate microsatellite repeats.

PMID- 8530064
TI  - A novel cDNA with homology to an RNA polymerase II elongation factor maps to
      human chromosome 5q31 (TCEB1L) and to mouse chromosome 11 (Tceb1l).
AB  - Few of the auxiliary factors that assist RNA polymerase II in the process of mRNA
      chain elongation have been identified. We have isolated a novel cDNA, Tceb1l,
      from mouse and human sources that encodes a 163-amino-acid protein and shows a
      significant level of identity with a recently identified RNA polymerase II
      transcription elongation factor, p15. Tceb1l is highly conserved throughout
      vertebrates and maps to mouse chromosome 11 and to the syntenic region of human
      chromosome 5q31. Tceb1l shows a restricted pattern of expression in the early
      mouse embryo, where it is absent from the neurectoderm; later Tceb1l is expressed
      in the caudal region of the neural tube, followed by widespread expression in
      many tissues, including the brain and spinal cord. These observations are
      consistent with Tceb1l being an RNA polymerase II elongation factor and suggest
      that Tceb1l/p15-like peptides may be a new family of proteins that influence RNA
      elongation.

PMID- 8530065
TI  - Detection of steroid 21-hydroxylase alleles using gene-specific PCR and a
      multiplexed ligation detection reaction.
AB  - Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal
      hyperplasia, an inherited inability to synthesize cortisol that occurs in 1 in
      10,000-15,000 births. Affected females are born with ambiguous genitalia, a
      condition that can be ameliorated by administering dexamethasone to the mother
      for most of gestation. Prenatal diagnosis is required for accurate treatment of
      affected females as well as for genetic counseling purposes. Approximately 95% of
      mutations causing this disorder result from recombinations between the gene
      encoding the 21-hydroxylase enzyme (CYP21) and a linked, highly homologous
      pseudogene (CYP21P). Approximately 20% of these mutations are gene deletions, and
      the remainder are gene conversions that transfer any of nine deleterious
      mutations from the CYP21P pseudogene to CYP21. We describe a methodology for
      genetic diagnosis of 21-hydroxylase deficiency that utilizes gene-specific PCR
      amplification in conjunction with thermostable DNA ligase to discriminate single
      nucleotide variations in a multiplexed ligation detection assay. The assay has
      been designed to be used with either fluorescent or radioactive detection of
      ligation products by electrophoresis on denaturing acrylamide gels and is readily
      adaptable for use in other disease systems.

PMID- 8530066
TI  - Human estrogen sulfotransferase gene (STE): cloning, structure, and chromosomal
      localization.
AB  - Sulfation is an important pathway in the metabolism of estrogens. We recently
      cloned a human liver estrogen sulfotransferase (EST) cDNA. We have now determined
      the structure and chromosomal localization of the EST gene, STE, as a step toward
      molecular genetic studies of the regulation of EST in humans. STE spans
      approximately 20 kb and consists of 8 exons, ranging in length from 95 to 181 bp.
      The locations of most exon-intron splice junctions within STE are identical to
      those found in a human phenol ST (PST) gene, STM, and in a rat PST gene. In
      addition, the locations of five STE introns are also conserved in the human
      dehydroepiandrosterone (DHEA) ST gene, STD. The 5'-flanking region of STE
      contains one CCAAT and two TATA sequences. The location of one of the TATA box
      elements is in excellent agreement with the site of transcription initiation as
      determined by 5'-rapid amplification of cDNA ends. STE was mapped to human
      chromosome 4q13.1 by fluorescence in situ hybridization. Cloning and structural
      characterization of STE will now make it possible to study potential molecular
      genetic mechanisms involved in the regulation of EST in human tissues.

PMID- 8530067
TI  - A YAC contig and an EST map in the pericentromeric region of chromosome 13
      surrounding the loci for neurosensory nonsyndromic deafness (DFNB1 and DFNA3) and
      limb-girdle muscular dystrophy type 2C (LGMD2C).
AB  - Two forms of inherited childhood nonsyndromic deafness (DFNB1 and DFNA3) and a
      Duchenne-like form of progressive muscular dystrophy (LGMD2C) have been mapped to
      the pericentromeric region of chromosome 13. To clone the genes responsible for
      these diseases we constructed a yeast artificial chromosome (YAC) contig spanning
      an 8-cM region between the polymorphic markers D13S175 and D13S221. The contig
      comprises 24 sequence-tagged sites, among which 15 were newly obtained. This
      contig allowed us to order the polymorphic markers centromere-D13S175-D13S141
      D13S143-D13S115-AF M128yc1-D13S292-D13S283-AFM323vh5- D13S221-telomere. Eight
      expressed sequence tags, previously assigned to 13q11-q12 (D13S182E, D13S183E,
      D13S502E, D13S504E, D13S505E, D13S837E, TUBA2, ATP1AL1), were localized on the
      YAC contig. YAC screening of a cDNA library derived from mouse cochlea allowed us
      to identify an alpha-tubulin gene (TUBA2) that was subsequently precisely mapped
      within the candidate region.

PMID- 8530068
TI  - A radiation hybrid map with 60 loci covering the entire short arm of chromosome
      12.
AB  - We present a high-resolution radiation hybrid map of the short arm of human
      chromosome 12 containing 60 loci, including 44 STSs within or closely associated
      with expressed sequences, 11 highly polymorphic markers, 2 anonymous sequences, 2
      subtelomeric sequences, and 1 centromeric sequence. The 60 loci fell into 48
      unique retention patterns, providing a comprehensive map covering the entire
      short arm of chromosome 12 with an average resolution of approximately 800 kb.
      Twenty-two unique positions were ordered in a 1000:1 framework map with an
      average resolution of 1.8 Mb. The proposed order is in good agreement with
      recently published genetic maps, high-resolution FISH maps, and YAC contigs. The
      noted inconsistencies involved neighboring loci permutations. Our observations
      further suggest the existence of chromosomal "hot spots" for breakage during
      irradiation. In three regions an usually high number of breaks was noted between
      neighboring loci compared to the physical distance derived from existing YAC
      contigs. Some of these hot spots seem to coincide with known chromosomal
      aberrations, of which at least two have been involved in the etiology of cancer.

PMID- 8530069
TI  - Cloning of the cDNAs for the small subunits of bovine and human DNA polymerase
      delta and chromosomal location of the human gene (POLD2).
AB  - cDNAs encoding the small subunit of bovine and human DNA polymerase delta have
      been cloned and sequenced. The predicted polypeptides, 50,885 and 51,289 Daltons,
      respectively, are 94% identical, similar to the catalytic subunits. The high
      degree of conservation of the polypeptides suggests an essential function for the
      small subunit in the heterodimeric core enzyme. Although the catalytic subunit of
      DNA polymerase delta shares significant homology with those of the herpes virus
      family of DNA polymerases, the small subunit of mammalian DNA polymerase delta is
      not homologous to the small subunit of either herpes simplex virus type 1 DNA
      polymerase (UL42 protein) or the Epstein-Barr virus DNA polymerase (BMRF1
      protein). Searches of the protein databases failed to detect significant homology
      with any protein sequenced thus far. PCR analysis of DNA from a panel of human
      hamster hybrid cell lines localized the gene (POLD2) for the small subunit of DNA
      polymerase delta to human chromosome 7.

PMID- 8530070
TI  - Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome
      9q22.3 and evaluation in non-insulin-dependent diabetes mellitus.
AB  - PCR primers specific to the human liver fructose-1,6-bisphosphatase (FBP) gene
      were designed and used to isolate a cosmid clone. Physical mapping of the FBP
      cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC
      = 0.35), located the liver FBP gene to chromosome 9q22.3 with no recombination
      between FBP and the index markers D9S196 (Zmax = 13.2), D9S280 (Zmax = 11.7),
      D9S287 (Zmax = 15.6), and D9S176 (Zmax = 14.4). Amplification using FBP exon
      specific primers with a YAC contig from this region of chromosome 9 further
      refined the placement of FBP genomic sequences to an approximately 1.7-cM region
      flanked by D9S280 and D9S287, near the gene for Fanconi anemia group C. Precise
      localization of the FBP gene enabled evaluation of FBP as a candidate gene for
      maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes
      (NIDDM) in both Caucasian and African-American families, using the highly
      informative markers D9S287 and D9S176. Although FBP is a rate-limiting enzyme in
      gluconeogenesis, using both parametric and nonparametric analysis there was no
      evidence for linkage of FBP to diabetes in these families.

PMID- 8530071
TI  - Gene structure and chromosomal localization of the human HSD11K gene encoding the
      kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) converts glucocorticoids to
      inactive products and is thus thought to confer specificity for aldosterone on
      the type I mineralocorticoid receptor in the kidney. Recent studies indicate the
      presence of at least two isozymes of 11 beta HSD. In vitro, the NAD(+)-dependent
      kidney (type 2) isozyme catalyzes 11 beta-dehydrogenase but not reductase
      reactions, whereas the NADP(+)-dependent liver (type 1) isozyme catalyzes both
      reactions. We have now characterized the human gene encoding kidney 11 beta HSD
      (HSD11K). A bacteriophage P1 clone was isolated after screening a human genomic
      library by hybridization with sheep HSD11K cDNA. The gene consists of 5 exons
      spread over 6 kb. The nucleotide binding domain lies in the first and the second
      exon, and the catalytic domain in the fourth exon. The 5' flanking sequences and
      first exon are GC-rich (80%), suggesting that the gene may be transcriptionally
      regulated by factors that recognize GC-rich sequences. Fluorescence in situ
      hybridization of metaphase chromosomes with a positive P1 clone localized the
      gene to chromosome 16q22. In contrast, the HSD11L (liver isozyme) gene is located
      on chromosome 1 and contains 6 exons; the coding sequences of these genes are
      only 21% identical. HSD11K is expressed at high levels in the placenta and kidney
      of midgestation human fetuses and at lower levels in lung and testes. Different
      transcriptional start sites are utilized in kidney and placenta. These data
      should be applicable to genetic analysis of the syndrome of apparent
      mineralocorticoid excess, which may represent a deficiency of 11 beta HSD.

PMID- 8530072
TI  - The mouse angiogenin gene family: structures of an angiogenin-related protein
      gene and two pseudogenes.
AB  - Angiogenin, a homologue of pancreatic ribonuclease, is a potent inducer of blood
      vessel formation. As an initial step toward investigating the in vivo functional
      role of this protein via gene disruption, we undertook the isolation of the
      angiogenin gene (Ang) from the 129 strain mouse, which will be used for
      generating targeting constructs. Unexpectedly, screening of a genomic library
      with an Ang gene probe obtained previously from the BALB/c strain yielded two new
      genes closely similar to Ang rather than Ang itself. One of these encodes a
      protein with 78% sequence identity to angiogenin and is designated "Angrp" for
      "angiogenin-related protein." The ribonucleolytic active site of angiogenin,
      which is critical for angiogenic activity, is completely conserved in Angrp,
      whereas a second essential site, thought to bind cellular receptors, is
      considerably different. Thus, the Angrp product may have a function distinct from
      that of angiogenin. The second gene obtained by library screening is a
      pseudogene, designated "Ang-ps1," that contains a frameshift mutation in the
      early part of the coding region. Although the Ang gene was not isolated from this
      library, it was possible to amplify this gene from 129 mouse genomic DNA by the
      polymerase chain reaction (PCR). Sequence analysis showed that the 129 strain Ang
      gene is identical to the BALB/c gene throughout the coding region. PCR cloning
      also yielded a second Ang-like pseudogene, designated "Ang-ps2." Southern
      blotting of genomic DNA confirmed the presence of Ang, Angrp, and at least one of
      the pseudogenes in an individual mouse and suggested that the mouse Ang gene
      family may contain more than the four members identified here.

PMID- 8530073
TI  - Differential gene expression in the murine thymus assayed by quantitative
      hybridization of arrayed cDNA clones.
AB  - High-throughput measurement of hybridization signatures obtained using complex
      probes prepared from poly(A)+ RNA and high-density cDNA colony filters is
      described. The performance of the system, elimination of artifacts, and
      verification of the validity of the data are discussed. cDNAs corresponding to
      sequences present at levels of approximately 0.01% in the complex probe can be
      detected. Good correlation is observed between expression profiles determined by
      this method and by Northern blotting. The method is applied to a preliminary
      investigation of differential expression in three cell types present in the
      murine thymus.

PMID- 8530074
TI  - Decreased cytochrome-c oxidase activity and lack of age-related accumulation of
      mitochondrial DNA deletions in the brains of schizophrenics.
AB  - Defects in mitochondrial energy production have been implicated in several
      neurodegenerative disorders, such as Parkinson disease and amyotrophic lateral
      sclerosis. To study the contribution of mitochondrial defects to Alzheimer
      disease and schizophrenia, cytochrome-c oxidase (COX) activity and levels of the
      mtDNA4977 deletion in postmortem brain tissue specimens of patients were compared
      with those of asymptomatic age-matched controls. No difference in COX activity
      was observed between Alzheimer patients and controls in any of five brain regions
      investigated. In contrast, schizophrenic patients had a 63% reduction of the COX
      activity in the nucleus caudatus (P < 0.0001) and a 43% reduction in the cortex
      gyrus frontalis (P < 0.05) as compared to controls. The average levels of the
      mtDNA4977 deletion did not differ significantly between Alzheimer patients and
      controls, and the deletion followed similar modes of accumulation with age in the
      two groups. In contrast, no age-related accumulation of mtDNA deletions was found
      in schizophrenic patients. The reduction in COX activity in schizophrenic
      patients did not correlate with changes in the total amount of mtDNA or levels of
      the mtDNA4977 deletion. The lack of age-related accumulation of the mtDNA4977
      deletion and reduction in COX activity suggest that a mitochondrial dysfunction
      may be involved in the pathogenesis of schizophrenia.

PMID- 8530075
TI  - Distribution of the mammalian Stat gene family in mouse chromosomes.
AB  - Studies of transcriptional activation by interferons and a variety of cytokines
      have led to the identification of a family of proteins that serve as signal
      transducers and activators of transcription, Stats. Here, we report that the
      seven mouse Stat loci map in three clusters, with each cluster located on a
      different mouse autosome. The data suggest that the family has arisen via a
      tandem duplication of the ancestral locus, followed by dispersion of the linked
      loci to different mouse chromosomes.

PMID- 8530076
TI  - Cloning of a new "finger" protein gene (ZNF173) within the class I region of the
      human MHC.
AB  - The human major histocompatability complex contains genes of both immune and
      nonimmune importance. Recently, several genes encoding novel, non-HLA products
      have been described in this area. We have performed positional cloning of short
      fragment cDNA sequences from the class I region of the human MHC using a
      hybridization selection approach. This report describes isolation of full-length
      cDNA clones and partial genomic clones that encode a protein that contains two
      domains rich in cysteine and histidine similar to those characteristic of metal
      dependent DNA binding proteins (C3HC4). The predicted protein also contains a
      domain thought to form a coiled-coil that may promote dimerization. A third
      feature is a polyglutamic acid region near the carboxyl terminus of the
      conceptual protein. Because of these properties, we have named this gene product
      acid finger protein (AFP). Although the biological role of AFP is unknown at
      present, one potential function is binding of nucleic acids. The gene (ZNF173) is
      expressed in multiple tissues and is conserved among mammals. In particular, the
      mouse and human coding regions are highly conserved. In addition to AFP, other
      related sequences have been localized to the MHC, suggesting that multiple AFP
      like genes exist in this area.

PMID- 8530077
TI  - Chromosomal structure of the human TYRP1 and TYRP2 loci and comparison of the
      tyrosinase-related protein gene family.
AB  - The structures of the human tyrosinase-related protein genes TYRP1 and TYRP2 have
      been determined and compared with that of the tyrosinase gene (TYR). The TYRP1
      protein is encoded in 7 exons spread over 24 kb of genomic DNA. Characterization
      of a 55-kb contig encompassing the human TYRP2 locus reveals that the protein
      coding region is divided into 8 exons. All three members of the TYRP gene family
      share a common C-terminal membrane spanning exon. Examination of the position of
      other intron junctions suggests that TYRP1 was derived from a TYR duplication and
      then was itself duplicated to give rise to the TYRP2 gene. The evidence also
      suggests that at least some of the introns within the TYR, TYRP1, and TYRP2
      coding regions were gained after duplication and that intron slippage is unlikely
      to have occurred.

PMID- 8530078
TI  - Isolation, characterization, and chromosomal localization of mouse and human COUP
      TF I and II genes.
AB  - Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are orphan
      members of the steroid/thyroid hormone receptor superfamily. COUP-TF homologues
      have been cloned in many species, from Drosophila to human. The protein sequences
      of COUP-TFs are highly homologous across species, suggesting functional
      conservation. Two COUP-TF genes have been cloned from human, and their genomic
      organizations have been characterized. To determine whether the genomic
      organization is conserved between human and mouse, we isolated two mouse COUP-TF
      genes (I and II) and characterized their genomic structures. Both genes have
      relatively simple structures that are similar to those of their human
      counterparts. In addition, we mapped mouse COUP-TF I to the distal region of
      chromosome 13 and COUP-TF II to the central region of chromosome 7. Furthermore,
      we mapped human COUP-TF I to 5q14 of chromosome 5 and COUP-TF II to 15q26 of
      chromosome 15. The results demonstrate that COUP-TF genes are located in
      chromosomal regions that are syntenic between mouse and human.

PMID- 8530079
TI  - A high-resolution map of genes, microsatellite markers, and new dinucleotide
      repeats from UBE1 to the GATA locus in the region Xp11.23.
AB  - Several new genes and markers have recently been identified on the proximal short
      arm of the human X chromosome in the area of Xp11.23. We had previously generated
      a YAC contig in this region extending from UBE1 to the OATL1 locus. In this
      report two polymorphic dinucleotide repeats, DXS6949 and DXS6950, were isolated
      and characterized from the OATL1 locus. A panel of YAC deletion derivatives from
      the distal portion of the contig was used in conjunction with the rest of the YAC
      map to position the new microsatellites and order other markers localizing to
      this interval. The marker order was determined to be DXS1367-ZNF81-DXS6849-ZNF21
      DXS6616-DXS 6950-DXS6949. In the proximal region below OATL1, we have isolated a
      pair of YACs from the GATA locus, B1026 and C01160. Mapping within these YACs
      indicates the orientation of DXS1126 and DXS1240, while a cosmid near the OATL1
      region reveals the overlap between the YAC contigs from the two loci. This cosmid
      contains the gene responsible for Wiskott-Aldrich syndrome (WAS) and localizes
      the disease gene between OATL1 and GATA. These data enable the expansion of the
      present physical map of the X chromosome from UBE1 to the GATA locus, covering a
      large portion of the Xp11.23 region. Genetic cross-overs in Xp11.23 support the
      marker orientation and the position of WAS, contrary to previous reports. With
      the integration of both physical and genetic maps we have predicted the following
      marker order: Xpter-UBE1-SYN1/ARAF1/ TIMP1-DXS1367-ZNF81-DXS.6849-ZNF21
      DXSy6616++ +-(OATL1, DXS6950-DXS6949)- WAS-(GATA, DXS1126)-DXS1240-Xcen.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8530080
TI  - Structure of the gene encoding the murine protein kinase CK2 beta subunit.
AB  - The mouse protein kinase CK2 beta subunit gene (Csnk2b) is composed of seven
      exons contained within 7874 bp. The exon and intron lengths extend from 76 to 321
      and 111 to 1272 bp, respectively. The lengths of the murine coding exons
      correspond exactly to the lengths of the exons in the human CK2 beta gene. Both
      genes contain a first untranslated exon. Also, the promoter regions from the
      human and murine CK2 beta gene share some common features, e.g., they contain
      neither a TATA nor a CAAT box, exon 1 is flanked by a cluster of CpG
      dinucleotides and recognition sequences for the HpaII restriction endonuclease,
      and several blocks of sequence in the 5' flanking region are conserved between
      mouse and human. Despite all of these common features, one of the most striking
      differences found concerns the human CK2 alpha subunit binding domain at position
      -170 to -239 of the human gene. This domain has no counterpart in the murine
      gene. Hence, regulation of transcription of the CK2 beta gene by the catalytic
      CK2 alpha subunit as was described by Robitzki et al. (J. Biol. Chem. 268: 5694
      5703, 1993) for the human gene cannot be considered a general regulatory
      mechanism.

PMID- 8530081
TI  - Regional localization of 64 cosmid contigs, including 18 genes and 14 markers, to
      intervals on human chromosome 9q34.
AB  - A fluorescence in situ hybridization map of distal human chromosome 9q has been
      produced by mapping cosmid clones to metaphase chromosomes with balanced
      reciprocal translocations. This is a very accurate method of mapping, as clones
      are localized by their position with respect to the breakpoint in addition to
      cytogenetic banding. By using three lymphoblastoid cell lines with translocation
      breakpoints within 9q34, we have localized 18 genes and 14 DNA markers to one of
      four intervals on the chromosome. Cosmid contigs exist around 16 of these genes
      and 12 of these markers. A further 43 contigs have also been mapped, but they are
      as yet anonymous.

PMID- 8530082
TI  - Structure and organization of the human glucose phosphate isomerase gene (GPI).
AB  - Two overlapping yeast artificial chromosome clones containing the human glucose 6
      phosphate isomerase gene (GPI) have been isolated. PCR and direct sequencing were
      used to determine the exon/intron structure of the gene. The gene spans in excess
      of 40 kb and consists of 18 exons ranging in size from 44 to 153 bp. All splice
      sites conform to the GT/AG rule.

PMID- 8530083
TI  - Localization of the gene encoding the human heat shock cognate protein, HSP73, to
      chromosome 11.
AB  - The heat shock cognate protein HSP73 (or HSC70) is a member of the HSP70
      multigene family. This protein has several functions, including binding to
      nascent polypeptides to facilitate correct folding and the uncoating of clathrin
      coated vesicles. Analysis of somatic cell hybrids by two-dimensional protein gel
      electrophoresis revealed the presence of a 73-kDa protein in two hybrids
      containing human chromosomes 5, 6, 9, and 11 in common. Using Western blot
      analysis, we demonstrate that this protein is a member of the HSP70 family and,
      by Southern blot analysis, that the HSP73 gene is located on human chromosome 11.
      Fluorescence in situ hybridization further localized HSP73 to the region 11q23.3
      q25. This region is involved in a number of genetic rearrangements and is
      associated with several well-characterized tumours.

PMID- 8530084
TI  - Organization and chromosomal localization of the gene (TAF2H) encoding the human
      TBP-associated factor II 30 (TAFII30).
AB  - The basal RNA polymerase II transcription factor, TFIID, is composed of the TATA
      binding protein (TBP) and 8-13 TBP-associated factors (TAFs) ranging from 250 to
      17 kDa. The structure of the human gene encoding the 30-kDa subunit of TFIID,
      TAF2H, has been determined. The gene consists of five exons (ranging from 66 to
      248 bp) and four introns (ranging from 83 to 211 bp). The transcription start
      site of the mRNA was mapped, and it shares a weak homology to the consensus of
      known initiator elements. Using in situ hybridization on human metaphase
      chromosomes, the TAF2H gene has been localized in the 11p15.2-p15.5 region of the
      human genome.

PMID- 8530085
TI  - Sequence characterization and genetic mapping of the human VSNL1 gene, a
      homologue of the rat visinin-like peptide RNVP1.
AB  - In the course of isolation and sequence analysis of microsatellite repeat
      containing human cDNAs, we have isolated the human homologue of the rat visinin
      like peptide gene. The human gene shows a high degree of conservation at both the
      amino acid and the DNA sequence level. The (CA)n microsatellite repeat embedded
      in the 3' untranslated region of the gene is conserved between rat and human,
      along with the flanking DNA sequences. We have mapped the VSNL1 gene to the short
      arm of chromosome 2.

PMID- 8530086
TI  - Chromosomal assignment and tissue distribution of novel expressed sequence tags
      from a human pancreatic islet cDNA library.
AB  - One hundred novel cDNAs from a human pancreatic islet library have been mapped
      using PCR and DNA from a human-rodent somatic cell hybrid mapping panel and/or
      fluorescence in situ hybridization. In addition, the pattern of expression of 54
      of these cDNAs has been determined by RNA blotting.

PMID- 8530087
TI  - A homozygous nonsense mutation in the alpha 3 chain gene of laminin 5 (LAMA3) in
      Herlitz junctional epidermolysis bullosa: prenatal exclusion in a fetus at risk.
AB  - Mutations in the three genes (LAMA3, LAMB3, and LAMC2) that encode the three
      chains (alpha 3, beta 3, and gamma 2, respectively) of laminin 5, a protein
      involved in epidermal-dermal adhesion, have been established as the genetic basis
      for the inherited blistering skin disorder, Herlitz junctional epidermolysis
      bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA
      from a child with H-JEB and identified a nonsense mutation in the alpha 3 chain
      gene (LAMA3) consisting of a homozygous C-to-T transition resulting in a
      premature termination codon (CGA-->TGA) on both alleles. The parents were shown
      to be heterozygous carriers of the same mutation. Direct mutation analysis was
      used to perform DNA-based prenatal diagnosis from a chorionic villus biopsy at 10
      weeks' gestation in a subsequent pregnancy. The fetus was predicted to be
      genotypically normal with respect to the LAMA3 mutation.

PMID- 8530089
TI  - A 405-kb cosmid contig and HindIII restriction map of the progressive myoclonus
      epilepsy type 1 (EPM1) candidate region in 21q22.3.
AB  - As a step toward identifying the molecular defect in patients afflicted with
      progressive myoclonus epilepsy type 1 (EPM1), we have assembled a cosmid contig
      of the candidate EPM1 region in 21q22.3. The contig constitutes a collection of
      87 different cosmids spanning 405 kb based on a derived HindIII restriction map.
      Potential CpG-rich islands have been identified based on the restriction map
      generated from eight different rare-cutting enzymes. This contig contains the
      genetic material required for the isolation of expressed sequences and the
      identification of the gene defective in EPM1 and possibly other disorders mapping
      to this region.

PMID- 8530088
TI  - Cloning and characterization of a human cDNA (INPPL1) sharing homology with
      inositol polyphosphate phosphatases.
AB  - We have cloned a novel human cDNA, INPPL1 (GenBank Accession No. L36818), which
      maps to 11q23. The corresponding mRNA is 4657 nt in length and is widely
      expressed in both fetal and adult tissues. An open reading frame of 3441 nt
      encodes a putative polypeptide that shares several domains with inositol
      triphosphate phosphatases. Several polymorphisms have been mapped to the 3'
      untranslated region, yet the putative coding region showed no polymorphisms in
      nine independent cDNA samples.

PMID- 8530090
TI  - Identification of an alternative transcript from the human iduronate-2-sulfatase
      (IDS) gene.
AB  - Iduronate-2-sulfatase (IDS) is involved in the degradation of heparan sulfate and
      dermatan sulfate in the lysosomes, and a deficiency in this enzyme results in
      Hunter syndrome. A 2.3-kb cDNA clone that contains the entire coding sequence of
      IDS has previously been reported. Here we describe the identification of a 1.4-kb
      transcript that may encode an IDS-like enzyme. The predicted protein is identical
      to the previously described enzyme, except for the absence of the 207-amino-acid
      COOH-terminal domain, which is replaced by 7 amino-acids. Our data suggest that
      there might exist an additional form of the IDS enzyme in humans. The results
      from this study may have implications for the pathogenesis of the Hunter
      syndrome.

PMID- 8530091
TI  - Mapping of the mouse macrophage inflammatory protein-1 alpha receptor gene Scya3r
      and two related mouse beta chemokine receptor-like genes to chromosome 9.
AB  - Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and RANTES are members of
      the beta chemokine family of leukocyte chemoattractants. We have previously
      cloned three mouse genes by cross-hybridization with the human MIP-1 alpha/RANTES
      receptor gene CMKBR1. One of the mouse genes, Scya3r, encodes a functional MIP-1
      alpha receptor. The functions of the other two, Scya3r-rs1 and Scya3r-rs2, are
      not known. We have now mapped Scya3r, Scya3r-rs1, and Scya3r-rs2 to chromosome 9,
      in a region of conserved synteny with the location of CMKBR1. Thus, like
      chemokine genes and alpha chemokine receptor genes, this group of beta chemokine
      receptor genes arose by tandem duplication.

PMID- 8530092
TI  - Expression pattern and mapping of the murine versican gene (Cspg2) to chromosome
      13.
AB  - Versican is a modular proteoglycan harboring a hyaluronan-binding domain at its
      amino-terminal end and a selectin-like domain at its carboxyl-terminal end,
      separated by a large intervening region containing the attachment sites for the
      glycosaminoglycan side chains. By virtue of its modular nature, versican may play
      a role in cellular attachment, migration, and proliferation by interacting with
      cell surfaces and extracellular matrix molecules. To discern the function of
      versican through the analysis of spontaneous and targeted genetic mutations, we
      have isolated a mouse versican cDNA encoding part of the hyaluronan-binding
      region, analyzed its mRNA expression in various adult mouse tissues and embryos,
      and determined the chromosomal location of the gene. Murine versican was 89%
      identical to human versican at the amino acid level and was highly expressed in
      mouse embryos at Days 13, 14, and 18. Expression was also detected in adult mouse
      brain, heart, lung, spleen, skeletal muscle, skin, tail, kidney, and testis.
      Using interspecific backcross analysis, we assigned the versican gene (Cspg2) to
      mouse chromosome 13, in a region that is syntenic with the long arm of human
      chromosome 5 where the human CSPG2 gene is located.

PMID- 8530093
TI  - Localization of the human stress responsive MAP kinase-like CSAIDs binding
      protein (CSBP) gene to chromosome 6q21.3/21.2.

PMID- 8530094
TI  - Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24
      p25.

PMID- 8530095
TI  - Assignment of a human homolog of the mouse Htr3 receptor gene to chromosome
      11q23.1-q23.2.

PMID- 8530096
TI  - Assignment of DAP1 and DAPK--genes that positively mediate programmed cell death
      triggered by IFN-gamma--to chromosome regions 5p12.2 and 9q34.1, respectively.

PMID- 8530097
TI  - Mouse hepatitis virus-3 induced prothrombinase (Fgl2) maps to proximal chromosome
      5.

PMID- 8530098
TI  - Localization of the gene encoding the putative human HLA class II associated
      protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence in situ hybridization.

PMID- 8530099
TI  - Structure of the mouse tyrosinase-related protein-2/dopachrome tautomerase
      (Tyrp2/Dct) gene and sequence of two novel slaty alleles.
AB  - We have isolated the eight exons and 5' and 3' flanking regions of the mouse
      tyrosinase-related protein-2 (dopachrome tautomerase) gene (Tyrp2/Dct), which is
      mutated in slaty mice. The gene has a structure that is considerably different
      from those of other tyrosinase family members in both the number and the position
      of introns, consistent with the suggestion that the divergence of the family
      represents an ancient gene duplication. We also identify in the 5' flanking DNA
      an 11-bp element, the M-box, conserved in other tyrosinase family genes. We have
      characterized point mutations in two slaty alleles recently identified at the
      Jackson Laboratory: slaty-2J (slt2J) has a similar phenotype to the original
      slaty (slt) mutation, and slaty light (Sltlt), which has a more severe effect and
      is semidominant. We suggest that the slaty-light phenotype is a result of the
      failure of the enzyme to be correctly targeted to its normal location on the
      inner face of the melanosomal membrane.

PMID- 8530100
TI  - Isolation and regional assignment of human chromosome 12p cDNAs.
AB  - We have characterized 117 cDNAs isolated by direct cDNA selection using pools of
      human chromosome 12p cosmids. Sequencing revealed that 41 clones did overlap with
      other cDNAs. Of the remaining 76 cDNA sequences, 11 matched previously identified
      human chromosome 12p genes and 3 matched previously determined cDNA sequences,
      including the retinoblastoma binding protein 2 (RBBP2), the cyclin-dependent
      kinase inhibitor KIP1, and an expressed sequence tag. For each of the 76 cDNAs
      specific selection by a genomic cosmid clone was confirmed. STSs were developed
      for all cosmids, among them 3 polymorphic simple sequence repeats associated
      with, respectively, the TNFR related protein, CD27, and SCNN1. Regional
      assignment of the STSs by PCR analysis with somatic cell hybrids and fluorescence
      in situ hybridization showed that the majority of the loci map to chromosome
      12p13, similar to the distribution of the known 12p genes. Evidence was found for
      the duplication on 12p of a region containing a polymorphic simple sequence
      repeat and sequences of two different cDNAs.

PMID- 8530101
TI  - cDNA sequence and gene locus of the human retinal phosphoinositide-specific
      phospholipase-C beta 4 (PLCB4).
AB  - Defects in the Drosophila norpA (no receptor potential A) gene encoding a
      phosphoinositide-specific phospholipase C (PLC) block invertebrate
      phototransduction and lead to retinal degeneration. The mammalian homolog, PLCB4,
      is expressed in rat brain, bovine cerebellum, and the bovine retina in several
      splice variants. To determine a possible role of PLCB4 gene defects in human
      disease, we isolated several overlapping cDNA clones from a human retina library.
      The composite cDNA sequence predicts a human PLC beta 4 polypeptide of 1022 amino
      acid residues (MW 117,000). This PLC beta 4 variant lacks a 165-amino-acid N
      terminal domain characteristic for the rat brain isoforms, but has a distinct
      putative exon 1 unique for human and bovine retina isoforms. A PLC beta 4
      monospecific antibody detected a major (130 kDa) and a minor (160 kDa) isoform in
      retina homogenates. Somatic cell hybrids and deletion panels were used to
      localize the PCLB4 gene to the short arm of chromosome 20. The gene was further
      sublocalized to 20p12 by fluorescence in situ hybridization.

PMID- 8530102
TI  - Chromosomal localization and cDNA cloning of the genes (DDB1 and DDB2) for the
      p127 and p48 subunits of a human damage-specific DNA binding protein.
AB  - DDB is a damage-specific DNA binding protein whose binding activity is absent
      from a minority of cell strains from individuals with xeroderma pigmentosum Group
      E, a human hereditary disease characterized by defective nucleotide excision DNA
      repair and an increased incidence of skin cancer. The binding activity from HeLa
      cells is associated with polypeptides of M(r) 124,000 and 41,000 as determined by
      SDS-polyacrylamide gels. This report describes the isolation of full-length human
      cDNAs encoding each polypeptide of DDB. The predicted peptide molecular masses
      based on open reading frames are 127,000 and 48,000. When expressed in an in
      vitro rabbit reticulocyte system, the p48 subunit migrates with an M(r) of 41 kDa
      on SDS-polyacrylamide gels, similarly to the peptide purified from HeLa cells.
      There is no significant homology between the derived p48 peptide sequence and any
      proteins in current databases, and the derived peptide sequence of p127 has
      homology only with the monkey DDB p127 (98% nucleotide identity and only one
      conserved amino acid substitution). Using a fluorescence in situ hybridization
      technique, the DDB p127 locus (DDB1) was assigned to the chromosomal location
      11q12-q13, and the DDB p48 locus (DDB2) to 11p11-p12.

PMID- 8530103
TI  - Chromosomal localization of mouse and human genes encoding the splicing factors
      ASF/SF2 (SFRS1) and SC-35 (SFRS2).
AB  - The mammalian SR-type splicing factors ASF/SF2 and SC-35 play crucial roles in
      pre-mRNA splicing and have been shown to shift splice site choice in vitro. We
      have mapped the ASF/SF2 gene in mice and humans and the SC-35 gene in mice.
      Somatic cell hybrid mapping of the human ASF/SF2 gene (SFRS1 locus) reveals that
      it resides on chromosome 17, and fluorescence in situ hybridization refines this
      localization to 17q21.3-q22. Recombinant inbred mapping of the mouse ASF/SF2 gene
      (Sfrs1 locus) and the mouse SC-35 gene (Sfrs2 locus) demonstrates that both genes
      are located in a part of mouse chromosome 11 that is homologous to human
      chromosome 17. Mapping of Sfrs1 using F1 hybrid backcross mice between the
      strains C57BL/6 and DDK places Sfrs1 very near the marker D11Mit38 and indicates
      that the ASF/SF2 gene is closely linked to the Ovum mutant locus.

PMID- 8530104
TI  - Isolation and characterization of the human MRE11 homologue.
AB  - Mutation of the Saccharomyces cerevisiae RAD52 epistasis group gene, MRE11,
      blocks meiotic recombination, confers profound sensitivity to double-strand break
      damage, and has a hyperrecombinational phenotype in mitotic cells. We isolated a
      highly conserved human MRE11 homologue using a two-hybrid screen for DNA ligase I
      interacting proteins. Human MRE11 shares approximately 50% identity with its
      yeast counterpart over the N-terminal half of the protein. MRE11 is expressed at
      the highest levels in proliferating tissues, but is also observed in other
      tissues. The MRE11 locus maps to human chromosome 11q21 in a region frequently
      associated with cancer-related chromosomal abnormalities. A MRE11-related locus
      was found on chromosome 7q11.2-q11.3.

PMID- 8530105
TI  - A 4-megabase YAC contig that spans the Langer-Giedion syndrome region on human
      chromosome 8q24.1: use in refining the location of the trichorhinophalangeal
      syndrome and multiple exostoses genes (TRPS1 and EXT1).
AB  - We have constructed a physical map covering over 4 Mb of human chromosome 8q24.1
      and used this map to refine the locations of the genes responsible for Langer
      Giedion syndrome. The map is composed of overlapping YAC clones that were
      identified and ordered in relation to sequence tagged sites mapped to the Langer
      Giedion chromosomal region on somatic cell hybrids. The minimal region of overlap
      of Langer-Giedion syndrome deletions, previously identified by analysis of 15
      patients, was placed on the map by analysis of 2 patients whose deletions define
      the endpoints. The chromosome 8 breakpoint of a balanced t(8;9)(q24.11;q33.3)
      translocation from a patient with trichorhinophalangeal syndrome (TRPS I) was
      found to be located just within the proximal end of the minimal deletion region.
      A deletion of 8q24.11-q24.3 in a patient with multiple exostoses was found to
      overlap the distal end of the LGS deletion region, indicating that the EXT1 gene
      is distal to the TRPS1 gene and supporting the hypothesis that Langer-Giedion
      syndrome is due to loss of functional copies of both the TRPS1 and the EXT1
      genes.

PMID- 8530106
TI  - Structural organization and genetic localization of the human bone morphogenetic
      protein 1/mammalian tolloid gene.
AB  - Bone morphogenetic protein 1 (BMP1) is a putative protease purified from extracts
      capable of inducing ectopic bone formation. A single mammalian gene apparently
      encodes alternatively spliced transcripts for BMP1, for a longer protein with a
      domain structure identical to that of the Drosophila dorsal-ventral patterning
      gene product tolloid (Tld), and for a third species of low abundance. Here we
      describe the organization of the 46-kb, 22-exon human BMP1/mTld gene that encodes
      these forms. Exons corresponding to each of the alternatively spliced transcripts
      are identified, and comparison with the Drosophila Tld gene reveals alignment of
      introns at only three positions. The major BMP1/mTld transcription start site is
      found only 706 bp downstream of the polyadenylation site of the SFTP2 surfactant
      gene, and a previously reported highly polymorphic CA repeat is found within the
      BMP1/mTld first intron. These two findings place the BMP1/mTld gene between
      markers D8S298 and D8S5 on the genetic map.

PMID- 8530107
TI  - Molecular cloning and structural characterization of the human histidase gene
      (HAL).
AB  - Histidase (EC 4.3.1.3) is a cytosolic enzyme that catalyzes the nonoxidative
      deamination of histidine to urocanic acid. Histidinemia, resulting from reduced
      histidase activity as reported in Cambridge stock his/his mice and in humans, is
      the most frequent inborn metabolic error in Japan. The histidase chromosomal gene
      (HAL) was isolated from a lambda EMBL-3 human genomic library using the human
      histidase cDNA as a probe. Restriction mapping and Southern blot analysis of the
      isolated clones reveal a single-copy gene spanning approximately 25 kb and
      consisting of 21 exons. Exon 1 encodes only 5' untranslated sequence of liver
      histidase mRNA, with protein coding beginning in exon 2. A rarely observed 5' GC,
      similar to that reported in the human P-450 (SCC) gene, is present in intron 20.
      All other splicing junctions adhere to the canonical GT/AG rule. A TATA box
      sequence is located 25 bp upstream of the liver histidase transcription
      initiation site determined by S1 nuclease protection analysis. Several liver- and
      epidermis-specific transcription factor binding sites, including C/EBP, NFIL6,
      HNF5, AP2/KER1, MNF, and others, are also identified in the 5' flanking region.
      Consistent with the hepatic and epidermal expression of histidase, this finding
      suggests that histidase transcription may be regulated by these factors. We
      further identify a polymorphism (A to G transition) in the histidase coding
      region of exon 16. The human histidase genomic structure presented here should
      facilitate the molecular investigation of symptomatic and asymptomatic forms of
      histidinemia.

PMID- 8530108
TI  - Insights for improving patient care.

PMID- 8530109
TI  - There is a place for nurses in medical schools.

PMID- 8530110
TI  - Our own worst enemy?

PMID- 8530111
TI  - Margaret Newman and the rhetoric of nursing theory.

PMID- 8530112
TI  - The evolution of targeted populations in a school-based tuberculin testing
      program.
AB  - A review of tuberculosis surveillance data from a program of school-based
      tuberculin testing demonstrates the natural evolution of targeted populations. In
      the 7 years encompassed by this study, the prevalence of tuberculin reactivity
      ranged from 4.3% to 6.1% in the Amarillo public school populations which were
      tested. The initial screening was a sampling of all students in the school
      district. In subsequent years' screening, the targeted populations were
      increasingly refined to eliminate lower-risk populations. Children enrolled in
      "English as a Second Language" (ESL) classes were found to have an 8.5%
      tuberculosis infection rate. The purpose of this study was to alert nurses that
      culturally sensitive approaches are needed for successful future testing.

PMID- 8530113
TI  - Validation of nursing management diagnoses.
AB  - Nursing management diagnosis based on nursing and management science, merges
      "nursing diagnosis" and "organizational diagnosis". Nursing management diagnosis
      is a judgment about nursing organizational problems. The diagnoses provide a
      basis for nurse manager interventions to achieve outcomes for which a nurse
      manager is accountable. A nursing organizational problem is a discrepancy between
      what should be happening and what is actually happening that prevents the goals
      of nursing from being accomplished. The purpose of this study was to validate 73
      nursing management diagnoses identified previously in 1992: 71 of the 72
      diagnoses were considered valid by at least 70% of 136 participants. Diagnoses
      considered to have high priority for future research and development were
      identified by summing the mean scores for perceived frequency of occurrence and
      level of disruption. Further development of nursing management diagnoses and
      testing of their effectiveness in enhancing decision making is recommended.

PMID- 8530114
TI  - Use of physiologic variables in nursing research.
AB  - In this study, the use of physiologic variables is described in research reports
      published 1989-1993 in four broad-based research journals. The National Institute
      for Nursing Research (NINR) emphasizes the need for more physiologically based
      nursing research. This analysis documents the current number and proportion of
      such research reported in four journals during a 5-year period. Each report was
      evaluated for the population sampled, type of physiologic variable, type of
      study, definitions, and reporting of reliability and validity measures. Among the
      763 reports, 114 (15%) examined physiologic variables. The most frequently
      studied physiologic variables were blood pressure, heart rate, and body
      temperature. The majority of studies posed and answered a clinical nursing
      question, and the study populations sampled were adults. Theoretical and
      operational definitions were included in most reports. Evidence of reliability
      and validity analysis were in 36% and 60% of the reports respectively. Although
      most nursing research focuses primarily on psychosocial aspects of care, several
      conceptual and psychometric issues were also addressed in studies that examined
      physiologic variables.

PMID- 8530115
TI  - Delineating the concept of hope.
AB  - This description of the concept of hope was developed using interview data from
      four participant groups: patients undergoing heart transplant, spinal cord
      injured patients, breast cancer survivors, and breastfeeding mothers intending to
      continue nursing while employed. Advanced techniques of concept analysis (using
      qualitative methods) enabled the delineation of the seven abstract and universal
      components of hope: a realistic initial assessment of the predicament or threat,
      the envisioning of alternatives and the setting of goals, a bracing for negative
      outcomes, a realistic assessment of personal resources and of external conditions
      and resources, the solicitation of mutually supportive relationships, the
      continuous evaluation for signs that reinforce the selected goals, and a
      determination to endure. Comparison of the various manifestations of these
      components in the four participant groups revealed unique and distinct patterns
      of hope. These were labeled: hoping for a chance, incremental hope, hoping
      against hope, and provisional hope. The implications for nursing practice are
      discussed.

PMID- 8530116
TI  - The art of comfort care.
AB  - Nursing art is defined and a template is presented for practicing one type of
      nursing art called comfort care. Propositions for comfort care are derived from a
      theory of comfort. Benefits are listed for integrating comfort care into
      practice. Testimony from a student who learned and applied comfort care provides
      support for its effectiveness as a learning tool. Comfort care is a holistic,
      individualistic, creative, and efficient model.

PMID- 8530117
TI  - Music, noise, and the human voice in the nurse-patient environment.
AB  - Sound is an essential and constant component of the human environment. Nurses
      have a responsibility to therapeutically manipulate the environment, but some
      have not fully recognized the significance of noise, voice, or music in the nurse
      patient milieu. This literature review provides a starting point for new studies
      that acknowledge the perception of sound as well as the physiological and
      psychological effects of sound on patients' well-being.

PMID- 8530118
TI  - Life event timing synchrony.
AB  - This paper traces the evolution of "life event timing" with particular emphasis
      on the derived concept, "life event timing synchrony." Life event timing
      synchrony refers to the degree to which an experience is perceived as harmonious
      and congruent with an individual's temporal expectations. Pregnancy serves as an
      illustration for application. Suggestions for further theoretical and empirical
      development are provided.

PMID- 8530119
TI  - Medical futility and nursing.
AB  - Defining medical futility is central to the efforts of clinicians and ethicists
      who seek to identify the limits of patient autonomy. This article is a critique
      of current efforts to define and then use policies of medical futility to justify
      refusing requests for treatment and care that have no perceived medical benefit.
      After exploring the current definitions of medical futility in the bioethics and
      clinical literature, comparisons of the advantages and disadvantages of the
      following three options are provided: allowing patients to decide all but
      physiologic futility, allowing clinicians to decide futility, and pursuing
      negotiated compromise. The third option--negotiated compromise--is recommended. A
      role is developed for nurses in preventing and resolving conflict about futile
      treatment.

PMID- 8530120
TI  - Preliminary validation of a measure of life support preferences.
AB  - A rapid, easy to use instrument that provides illustrations of life support
      choices can enhance discussion of life support measures with patients. The goal
      of this preliminary study was to develop and validate an instrument, the Life
      Support Preferences Questionnaire (LSPQ). In a convenience sample of 116 healthy
      adults, the LSPQ showed a sturdy degree of internal consistency for a short
      measure. The 2-week stability evidence was supportive of respondents' consistent
      attitudes over time at both the item and scale level. Principal factor analyses
      give evidence there is one dominant theme underlying the items. Use of the LSPQ
      with hospitalized patients is being explored as a response to policy changes
      resulting from the 1991 Patient Self-Determination Act.

PMID- 8530121
TI  - Reversal theory's mastery and sympathy states in smoking cessation.
AB  - Relapse is the most frequent outcome of smoking cessation attempts. This study
      tests the usefulness of the mastery and sympathy concepts of Apter's reversal
      theory to explain whether subjects lapse or abstain during highly tempting
      situations. Descriptions of the highly tempting situations of 57 individuals who
      were attempting to quit smoking were assigned to mastery or sympathy categories.
      Situations were also coded for availability of cigarettes. Logit modeling
      revealed that both the mastery/sympathy variable and the availability of
      cigarettes were necessary to fit the data. Being in the mastery state and having
      to exert effort to get cigarettes were significantly related to resisting the
      urge to smoke. The smoking status of 36% of the subjects was correctly classified
      using both variables. The usefulness of mastery/sympathy states in explaining
      relapses in behavior change is discussed.

PMID- 8530122
TI  - Relationships between nurse-expressed empathy, patient-perceived empathy and
      patient distress.
AB  - It is increasingly important that nursing care be associated with measurable
      patient outcomes. A correlational study examined relationships between nurse
      expressed empathy and two patient outcomes: patient perceived empathy and patient
      distress. Subjects (N = 140) were randomly selected from RNs and patients on
      medical and surgical units in two urban, acute care hospitals. Nurse-subjects (N
      = 70) completed two measures of nurse-expressed empathy: the Behavioral Test of
      Interpersonal Skills and the Staff-Patient Interaction Response Scale. Patient
      subjects (N = 70) completed the Profile of Mood States, the Multiple Affect
      Adjective Checklist, and the Barrett-Lennard Relationship Inventory. Findings
      indicated a negative relationship (r = .71, p < .001) between a set of empathy
      variables and a set of patient distress variables and a positive relationship
      between nurse-expressed and patient perceived empathy (r = .37-.47, p < .05).
      This study is one of the first to link behavioral measures of nurse empathy to
      patient outcomes.

PMID- 8530123
TI  - The Pinwheel Model of Bereavement.
AB  - The Pinwheel Model of Bereavement is a process-orientated model of grief which
      recognizes loss as a unique lived experience. The model and relevant nursing
      response are described using Margaret Newman's nursing theory of health as
      expanding consciousness. The model is based on research by Carter (1989) and
      clinical experience. The contextual theme for the model is "personal history."
      Six core themes are: being stopped, hurting, missing, holding, seeking, and
      valuing. Three meta themes are change, expectations, and inexpressibility.
      Capacities for "being with" the bereaved are identified for the practice of
      nursing.

PMID- 8530124
TI  - [Reactive oxygen species].

PMID- 8530125
TI  - [Reactive oxygen species and arachidonic acid metabolites of polymorphonuclear
      leukocytes].
AB  - The activation of polymorphonuclear leukocytes by stimulants from host or
      parasites leads to various metabolic processes and to enhanced oxygen uptake.
      Oxygen is enzymatically processed to from reactive oxygen compounds and
      metabolites of arachidonic acid which are involved in killing of microbial
      pathogens and influence many processes in inflammation. Their activities are
      regulated intracellularly by antioxidants. A lack or exhaustion of these systems
      may lead to cell and organ damage in which DNA, proteins, lipids and sugars may
      be involved. Antioxidants and inhibitors of the arachidonic acid metabolism are
      applied to reduce these pathological changes. An essential aspect of microbial
      pathogenicity is the multifold modification of the formation of reactive oxygen
      compounds and arachidonic acid metabolites.

PMID- 8530126
TI  - [Effects of the oxidizing agents ozone and nitrogen dioxide on the lung: studies
      of a cell culture model].
AB  - In experimental exposure studies with ozone or nitrogen dioxide a change in lung
      function and unspecific airway sensitivity was observed. These effects were
      paralleled by an induction of cellular and biochemical changes. The exposure of
      isolated cells in vitro led to a decrease in vitality, an increase in
      permeability and the secretion of mediators very similar to the composition found
      in bronchoalveolar lavage after in vivo exposure. The cell culture model,
      therefore, allows the study of the mechanism of these oxidative air pollutants
      and allows further the understanding of the influence of different cell types on
      the observed effects in vivo.

PMID- 8530127
TI  - [Lung function and prevalence of irritation of eyes and respiratory airways on
      days with elevated ozone concentrations].
AB  - In order to evaluate potential health effects on days with elevated ozone
      concentrations, lung function parameters and subjective votes on irritations of
      eyes and airways were taken repeatedly from subjects belonging to four assumed
      ozone risk groups and one control group (at least 40 subjects each) - senior
      citizens, juvenile asthmatics, forestry workers, athletes and clerks - in
      comparison of days with elevated (at least 100 micrograms/m3) and low ozone
      concentrations (at most 80 micrograms/m3). The results show no relevant ozone
      effects for the groups, "senior citizens" and "athletes", only minor pulmonary
      effects for "juvenile asthmatics", but significantly higher airway resistances on
      "ozone days" for "forestry workers" (by 21%) and "clerks" (by 16%). On days with
      moderately elevated levels of ozone in the environment it is assumed that ozone
      itself has minor influence on pulmonary responses compared to that of other
      constituents of the air in certain location like forest or indoors.

PMID- 8530128
TI  - [Antioxidants in nutrition and their importance in the anti-/oxidative balance in
      the immune system].
AB  - Free radicals and reactive oxygen species can damage cells and tissues of
      biological organisms. Due to the fact that these compounds are generated
      continuously in living cells defense mechanisms must exist. This so-called
      antioxidative system ensures that the formation of free radicals during different
      physiological processes does not result in cellular damage. Free radicals
      (oxidants) are produced form the immune system. The purpose of this immune cell
      products is to destroy invading organisms and damaged tissue. Oxidants enhance IL
      1, IL-8 and TNF production in response to inflammatory stimuli. Sophisticated
      antioxidant defense systems like enzymes or vitamins protect directly and
      indirectly the host against the damaging influence of oxidants. While endogenous
      systems can hardly be influenced, exogenous antioxidants, delivered by the diet,
      can be upregulated in the body. By this way the pro-/antioxidative capacity can
      be balanced or even unbalanced.

PMID- 8530129
TI  - [Clinical significance of reactive oxygen species].
AB  - There is increasing evidence that reactive oxygen substances are involved in the
      pathogenesis and/or progression of differ diseases. A short introduction to the
      biochemistry of reactive oxygen substances will be given in this review.
      Subsequently, the role of reactive oxygen substances will be discussed
      exemplarily on pathophysiological aspects of neutrophil granulocytes and of
      neurodegenerative diseases.

PMID- 8530130
TI  - [Viruses and cancer: molecular pathologic mechanisms of viral carcinogenesis].
AB  - At least 15% of the human cancer incidence is caused by an infection with human
      tumor viruses. The recent progress of experimental cancer research led to
      important new concepts about the pathomechanisms of viral carcinogenesis. The
      functional inactivation of cellular tumor suppressor proteins by viral factors
      appears to be a key event in the process of virus-associated malignant cell
      transformation. This review summarizes the current concepts about the interaction
      between viral oncoproteins and cellular tumor suppressor proteins and evaluates
      their significance for individual tumor viruses and their associated cancers.

PMID- 8530131
TI  - [Nosocomial transmission of pneumococcus].
AB  - Increasing resistance of pneumococci against antimicrobial agents in several
      parts of the world is reported. We observed a probably nosocomial transmission of
      a pneumococcal strain with reduced susceptibility to penicillin (capsular type
      6A). Recommendations for diagnostic procedures in the laboratory and therapy are
      given.

PMID- 8530132
TI  - [Case report: treatment of anti-basement membrane glomerulonephritis with
      immunoadsorption].
AB  - Immunoadsorption (IMAD) is a particle extracorporeal therapy in treatment of
      various autoimmune diseases which differs from plasmapheresis. In the case
      presented here IMAD was helpful in the therapy of an acute renal failure due to
      an antiglomerular basement membrane disease. IMAD resulted in a quick recovery
      and stabilisation of the renal function. In addition to IMAD, the patient was
      treated with steroids, an immunosuppressive therapy was started immediately after
      IMAD. Considering the course of this patient's disease, we are convicted that
      IMAD was a major factor in the therapeutic success. IMAD was well tolerated by
      the patient, no side effects were seen.

PMID- 8530133
TI  - Special issue: Transcription Factors in Immunology. Proceedings of a conference.
      Munchen, Germany, October 27-28, 1994.

PMID- 8530134
TI  - Multi-step activation of NF-kappa B/Rel transcription factors.
AB  - Transcription factors belonging to the NF-kappa B/Rel family are specialized in
      the transduction of primarily pathogenic signals from the cytoplasm to the cell
      nucleus. To date, the family comprises five distinct DNA-binding subunits and
      five regulatory proteins with inhibitory function, called I kappa B proteins. The
      interaction of dimers of the DNA-binding subunits with the I kappa B proteins
      leads to the cytoplasmatic retention of the complex and inhibition of its DNA
      binding. Following stimulation of cells, the I kappa B proteins become
      phosphorylated and are subsequently degraded, presumably, by the proteasome. The
      released NF-kappa B/Rel transcription factors can then enter the nucleus, bind to
      decameric DNA cognate sequences and stimulate transcription of numerous
      immunologically important target genes. In this article, we discuss several
      distinct levels at which the NF-kappa B/Rel transcription factors can be
      regulated.

PMID- 8530135
TI  - Activation of NF-kappa B by the Tax protein of HTLV-1.
AB  - The Tax protein, encoded by the human T cell leukemia virus HTLV-1, is
      responsible for transcriptional activation of the viral genome through conserved
      21bp repeats located in its promoter. Tax also activates the transcription of
      cellular genes such as interleukin 2, interleukin 2 receptor (IL2R), GM-CSF,
      vimentin, c-fos, c-jun as well as the major histocompatibility complex class I
      genes. Tax does not bind DNA directly, but seems to activate transcription
      indirectly by enhancing the activity of the transcription factors that recognize
      responsive elements located in the promoters of the Tax-responsive genes, or by
      forming ternary complexes with these factors and DNA. One class of target sites
      for Tax are the kappa B sequences which are bound by members of the rel/NF-kappa
      B family. It has been previously shown that Tax is able to induce nuclear
      translocation of NF-kappa B. The activity of the NF-kappa B transcription factor
      is normally controlled through cytoplasmic retention by either of two types of
      molecules: the inhibitor I kappa B alpha/MAD3 or the p105 and p100 precursors of
      the p50 and p52 DNA-binding subunits. Treatment of cells with classical NF-kappa
      B inducers like TNF, IL-1, PMA or LPS results in MAD-3 degradation followed by
      nuclear translocation of NF-kappa B. On the other hand, the mechanisms involved
      in the dissociation of the cytoplasmic p105/p100-containing complexes are largely
      unknown. We demonstrate here that Tax can induce translocation of members of the
      NF-kappa B family retained in the cytoplasm through interaction with either p105
      or p100. On the other hand Tax induces no apparent degradation of MAD-3. These
      results suggest that Tax activates NF-kappa B essentially through the p105/p100
      retention pathway.

PMID- 8530136
TI  - Regulation of the c-fos promoter.

PMID- 8530137
TI  - Both ATF-2 and c-Jun are phosphorylated by stress-activated protein kinases in
      response to UV irradiation.

PMID- 8530138
TI  - The NF-jun transcription factor in the hematopoietic response to mitogenic
      signals.

PMID- 8530139
TI  - Positive regulation of the nuclear activator CREM by the mitogen-induced p70 S6
      kinase.

PMID- 8530140
TI  - Molecular principles of Oct2-mediated gene activation in B cells.
AB  - The octamer motif is a crucial regulatory element for immunoglobulin promoter and
      enhancer function. We have investigated the molecular mechanisms that underlie
      octamer-mediated gene activation in B cells. This B cell-specific transcriptional
      regulation is subject to a novel type of regulatory mechanism. We could
      demonstrate that octamer-dependent transcription is not only regulated by
      specific DNA-binding transcription factors, but in addition requires the activity
      of B cell-restricted cofactors. Both octamer-dependent promoter and enhancer
      activation depend on such a combination of transcription factor and cofactors.
      However, the exact requirements differ for these two situations. Promoter
      activity can be achieved with either one of two distinct transcription factors,
      Oct1 and/or Oct2, together with the cofactor OCA-B1. In contrast, only Oct2 in
      conjunction with an additional cofactor, OCA-B2, can confer enhancer activity.

PMID- 8530141
TI  - The C/EBP family of transcription factors.
AB  - The C/EBP proteins form a family of transcription factors with at least seven
      members. These proteins consist of three structural components which include a C
      terminal leucine-zipper, a basic DNA-binding region and a N-terminal
      transactivating region. Dimerization through the leucine-zipper leads to
      formation of homo- and heterodimers which then bind with their two basic regions
      to often non-symmetric DNA-sequences in the promoter/enhancer regions of a
      variety of genes. Expression of C/EBP is prominent in adipocytes, hepatocytes and
      monocytes/macrophages, and here these proteins are involved in tissue-specific
      gene expression. Target genes for C/EBP include those for acute phase response
      genes in liver cells and for cytokine genes in monocytes/macrophages. Therefore,
      intervention at the level of C/EBP transcription factors may prove effective in
      controlling immune response.

PMID- 8530142
TI  - Tumor necrosis factor alpha increases expression of adenovirus E3 proteins.
AB  - Human adenovirus can cause persistent infections in man. Implicated in this
      phenomenon is the early transcription unit 3 (E3) of the virus which encodes
      proteins that are primarily devoted to counteract the lytic attack by the host
      immune system: Several E3 proteins (14.7K, 10.4K and 14.5K) protect infected
      cells from the lytic activity of tumor necrosis factor alpha (TNF) while the most
      abundant E3 protein, E3/19K, inhibits lysis by cytotoxic T cells. E3/19K
      interacts with class I histocompatibility (MHC) antigens in the rough endoplasmic
      reticulum, thereby preventing transport of MHC molecules to the cell surface and,
      consequently, MHC-restricted T cell recognition. In addition, the 10.4K and 14.5K
      proteins downregulate cell surface expression of the epidermal growth factor
      receptor. Interestingly, adenovirus-mediated pneumonia in mice is accompanied by
      induction of TNF, a cytokine known to enhance MHC expression. We previously
      showed that TNF is unable to restore MHC class I expression in E3/19K transfected
      cells but rather leads to a further reduction of MHC antigens. This effect
      correlated with an increased production of E3/19K mRNA and protein. We now find
      in addition an upregulation of other E3 proteins in transfected as well as in
      infected cells. This coordinated upregulation of E3 proteins indicates that TNF
      stimulates the E3 promoter, probably by activating the transcription factor NF
      kappa B. Thus, a novel interaction between the immune system and adenovirus is
      described in which the virus takes advantage of an immune mediator to promote
      expression of several immunosubversive proteins supporting its escape from
      immunosurveillance.

PMID- 8530143
TI  - TNF-induced activation of NF-kappa B.
AB  - Tumor Necrosis Factor (TNF) is one of the most potent physiological inducers of
      the nuclear transcription factor NF-kappa B. In light of the pivotal role of NF
      kappa B in the development of immune responses and activation of HIV replication,
      the identification of TNF signal transduction pathways involved in NF-kappa B
      activation is of particular interest. Data from our laboratory demonstrate that
      the TNF signal transduction pathway-mediating NF-kappa B activation involves two
      phospholipases, a phosphatidylcholine-specific phospholipase C (PC-PLC) and an
      endosomal acidic sphingomyelinase (aSMase). The aSMase activation by TNF is
      secondary to the generation of 1,2-diacylglycerol (DAG) produced by a TNF
      responsive PC-PLC. SMase and its product ceramide induce degradation of the NF
      kappa B inhibitor I kappa B as well as NF-kappa B activation. Besides endosomal
      acidic SMase, TNF also rapidly activates a plasmamembrane-associated neural SMase
      (nSMase), that, however is not involved in TNF-induced NF-kappa B activation.
      NSMase and aSMase are activated by different cytoplasmic domains of the 55 kDa
      TNF-receptor and are coupled to select pathways of TNF signaling. Ceramide
      generated by nSMase directs the activation of proline-directed serin/threonine
      protein kinases and phospholipase A2 and ceramide produced by aSMase triggers the
      activation of NF-kappa B. No apparent crosstalk was detected between nSMase and
      aSMase pathways, indicating that ceramide action depends on the topology of its
      production.

PMID- 8530144
TI  - Influence of redox status of lymphocytes and monocytes on HIV transcription and
      replication.

PMID- 8530145
TI  - Transcriptional regulation of the tumor necrosis factor alpha gene.

PMID- 8530146
TI  - Tolerance to lipopolysaccharide in human blood monocytes.
AB  - When monocytes are stimulated with Lipopolysaccharide (LPS), they efficiently
      produce cytokines like tumor necrosis factor (TNF). Upon secondary stimulation,
      this response is only minimal, and there is little TNF mRNA transcription, mRNA
      accumulation, and protein production. Studies with the monocytic cell line Mono
      Mac 6 have shown that in such tolerant cells the CD14 LPS receptor is still
      present, and the transcription factor NF-kB is still efficiently mobilized. This
      NF-kB complex has, however, a different composition, that does not transactivate
      TNF promoter reportergene constructs. We now show that similar mechanisms apply
      to primary blood monocytes. After primary stimulation these cells also produce
      high levels of TNF and then develop tolerance in that upon secondary challenge
      little TNF is produced. CD14 cell surface expression is unchanged or even
      increased in tolerant cells and NF-kB mobilization does still occur. The complex
      mobilized in such tolerant monocytes is, however, composed mainly of high
      mobility binding proteins. This indicates that p50 homodimers predominate in NF
      kB complex of tolerant blood monocytes, similar to what has been reported for
      Mono Mac 6 cells. The data add to the notion that p50 binding to the cognate -kB
      DNA motif in the TNF promoter may be responsible for the unresponsiveness in LPS
      tolerance.

PMID- 8530147
TI  - Regulation of IL-1 beta expression by cyclic AMP in myeloid cells.

PMID- 8530148
TI  - Regulation of HLA class I loci by interferons.

PMID- 8530149
TI  - C-myc represses transiently transfected HLA class I promoter sequences not locus
      specifically.
AB  - Overexpression of the c-myc oncogene is frequently accompanied by downregulation
      of Major Histocompatibility Complex (MHC, HLA in humans) class I antigens. In
      human melanoma c-myc overexpression downmodulates HLA-B expression, whereas HLA-A
      is hardly affected. Repression of HLA-B is mediated through the core promoter,
      containing a CAAT-box and a non-conventional TATA-box. We show evidence that in
      transient transfection assays the HLA-A2 and HLA-B7 promoters are repressed by c
      myc to the same extent. Therefore, other sequences of the HLA-A and HLA-B genes,
      possibly intron/exon sequences, should contribute to the locus B-specificity of
      the downregulation. Furthermore, c-myc does not seem to alter binding of protein
      complexes to the CAAT- or TATA-box of HLA-B7 or HLA-A2 in gel retardation assays.
      Comparison of promoters repressed by c-myc reveals a weak consensus sequence of
      the initiator (Inr) element: TCA(+1)YYYNY. The presence of a TCA sequence in the
      initiator region of the MHC class I promoter makes downregulation by c-myc
      through the Inr likely. We speculate that the Inr contributes to MHC class I
      promoter activity by stimulating recruitment of TFIID to the weak, non
      conventional TATA-box, thereby making it susceptible to repression by c-myc
      through the Inr.

PMID- 8530150
TI  - Regulation of MHC class II gene expression.

PMID- 8530151
TI  - The interplay between lymphoid-specific and ubiquitous transcription factors
      controls the expression of interleukin 2 gene in T lymphocytes.

PMID- 8530152
TI  - The cis-acting elements controlling mouse IL-2R alpha transcription.

PMID- 8530153
TI  - NF-Y, IRF-2, and C/EBP proteins are involved in regulation of human IL-4 gene
      expression.

PMID- 8530154
TI  - The inducible transcription factor NF-AT plays an important role in the
      activation of the murine interleukin-4 promoter.

PMID- 8530155
TI  - The nuclear factor IL-4 (NF-IL4).

PMID- 8530156
TI  - Circumvention of tolerance for the nuclear T cell protein TCF-1 by immunization
      of TCF-1 knock-out mice.
AB  - Molecular events that underlie the well-defined phenotypic changes of the
      differentiating thymocyte are poorly understood. A candidate gene to control
      thymocyte differentiation, T cell factor-1 (TCF-1)* encodes a DNA-binding
      protein. Its mRNA expression pattern is complex during embryogenesis, yet
      restricted to lymphocytes postnatally. Expression studies on TCF-1 protein have
      been hampered by the difficulty to raise antibodies due to extreme evolutionary
      conservation. TCF-1 knock-out mice, generated recently in our laboratory, have
      strongly decreased numbers of thymocytes, but are otherwise normal. We have used
      these mice to generate anti-TCF-1 antibodies. By immunization with a recombinant
      fusion protein, we show that TCF-1 knock-out mice readily yield antiserum titers
      against human and mouse TCF-1 protein. Wild-type littermates remain unresponsive
      to TCF-1 while they mount a high-titer antibody response to the fusion protein,
      Maltose Binding Protein (MBP). Subsequently, TCF-1-specific hybridomas could be
      prepared from the spleens of immunized knock-out mice. This study illustrates the
      almost complete tolerance of mice for human TCF-1 and demonstrates that this
      tolerance is readily broken by gene knock-out. Furthermore, the usefulness of
      knock-out mice for the generation of monoclonal antibodies against the gene
      product of interest is underscored.

PMID- 8530157
TI  - Transcriptional regulation of the human T cell receptor delta gene.
AB  - T cell receptor delta gene expression is regulated by a T cell-specific
      transcriptional enhancer located within the J delta 3-C delta intron. An
      essential element of the enhancer was localized to a small 30 bp segment denoted
      delta E3. Two specific factors, CBF/PEBP2 and c-Myb, bind to adjacent sites
      within delta E3 and cooperate functionally to mediate transcriptional activation.
      These factors are likely to play essential roles in the developmental activation
      of the TCR delta gene in vivo.

PMID- 8530158
TI  - Transcriptional regulation of the human intercellular adhesion molecule-1 gene: a
      short overview.
AB  - Human intercellular adhesion molecule-1 (ICAM-1), a transmembrane glycoprotein
      that functions as a ligand for lymphocyte function-associated antigen-1, plays an
      important role in mediating cell-cell interactions in inflammatory reactions. It
      is induced by proinflammatory cytokines such as interleukin-1, tumor necrosis
      factor-alpha or interferon-gamma, as well as by phorbol esters, retinoic acid and
      lipopolysaccharide. Furthermore, ICAM-1 is upregulated by interleukin-6, which
      suggests that it belongs to the family of acute phase response genes.
      Investigation of the 5'-regulatory region of the human ICAM-1 gene revealed
      sequence motifs for a variety of transcription factors implicated in
      transcriptional regulation. This review summarizes the current knowledge of the
      transcriptional regulation of the human ICAM-1 gene.

PMID- 8530159
TI  - Intercellular adhesion molecule 1 (ICAM-1) is synergistically activated by TNF
      alpha and IFN-gamma responsive sites.
AB  - Human ICAM-1 expression can be upregulated by IFN-gamma or TNF-alpha and is
      synergistically increased by a combination of both cytokines. Transient
      transfections of ICAM-1/luciferase constructs identified two regulatory regions
      mediating the cytokine responses and both were found to be necessary for
      synergism. Using electrophoretic mobility shift assays and specific antibodies we
      observed that the NF-kappa B like sequence at -187 bound both p65/p50 and p65/c
      Rel in the presence of TNF-alpha, while the interferon responsive region at -75
      bound Stat1 alpha (p91). Treatment with IFN-gamma together with TNF-alpha did not
      lead to any additional or enhanced bands, suggesting that both transcription
      factor complexes function independently to increase the transcription initiation.

PMID- 8530160
TI  - Regulation of expression of the LFA-1 and p150,95 leukocyte integrins:
      involvement of the CD11a and CD11c gene promoters.
AB  - Human Lymphocyte Associated Antigen-1 (LFA-1, CD11a/CD18, alpha L/beta 2) and
      p150,95 (CD11c/CD18, alpha X/beta 2) are cell surface alpha/beta heterodimers
      that, together with Mac-1 (CD11b/CD18, alpha M/beta 2) comprise the leukocyte
      restricted beta 2 subfamily of integrins. LFA-1 is the only integrin expressed on
      all leukocyte lineages while p150,95 is exclusively expressed on cells of the
      myeloid lineage and on activated B lymphocytes and natural killer cells. The
      expression of the leukocyte integrins is regulated during cell activation and
      differentiation by transcriptional mechanisms. To dissect the molecular basis for
      the tissue-restricted and developmentally regulated expression of LFA-1 and
      p150,95, the promoter regions of their corresponding alpha subunits (CD11a and
      CD11c) were isolated and functionally characterized. Both promoters lack TATA and
      CAAT boxes, but exhibit initiator-like sequences at their major transcriptional
      start sites. Transient expression of CD11a- and CD11c-based reporter gene
      constructs have demonstrated the involvement of both promoters in the tissue
      specific expression of LFA-1 and p150,95. Furthermore, a combination of DNAse I
      protection experiments and mobility band shift assays have revealed the existence
      of numerous DNA-protein interactions at the proximal region of both promoters,
      some of which overlap with consensus binding sequences for known transcription
      factors and correlate with the pattern of expression of both integrins.

PMID- 8530161
TI  - Control of cytokeratin 17 expression by interferon gamma.

PMID- 8530162
TI  - Activity of Stat family transcription factors is developmentally controlled in
      cells of the macrophage lineage.
AB  - Stat family transcription factors are activated in response to a variety of
      cytokines to bind to a class of DNA elements termed gamma interferon activation
      site (GAS)-like elements. Here we investigate two GAS-binding transcription
      factors, the gamma-interferon activation factor (GAF) and the differentiation
      induced factor (DIF) that are activated by interferon-gamma (IFN-gamma) in U937
      cells. Treatment of U937 cells with phorbol ester (TPA) induces differentiation
      from a promonocyte into a monocyte stage of macrophage development. Monocytic
      differentiation led to an increased transcriptional response of GAS-containing
      genes to IFN-gamma. TPA treatment also caused a profound change in the IFN-gamma
      activation of GAF and DIF. GAF DNA-binding activity was activated much better in
      the monocyte stage and the GAF constituent Stat 1 showed increased
      phosphorylation. In contrast, DIF activation by IFN-gamma was found in
      promonocytes but was virtually absent in monocytes. Moreover, DIF activation was
      observed during TPA-induced monocytic differentiation and after treatment of
      macrophages with the macrophage differentiation factor CSF-1. Our data suggest
      DIF to be part of a developmental program leading to terminal macrophage
      differentiation and GAF to be a transcription factor bringing about the stronger
      activation response of mature macrophages to IFN-gamma.

PMID- 8530163
TI  - Promoter analysis of the human interleukin-8 receptor genes, IL-8RA and IL-8RB.
AB  - Two distinct receptors for the neutrophil chemoattractant IL-8 have been cloned,
      designated IL-8RA and -B. Both receptors are abundantly expressed on unstimulated
      mature neutrophils. To understand the tissue-specific expression and to identify
      gene-regulatory elements we have cloned, sequenced and characterized both human
      IL-8R genes, IL-8RA and -B. The open reading frames and 3'-untranslated regions
      were entirely encoded by a single exon. The promoters of both IL-8R-genes
      appeared to be very similar: A non-classical TATA-box and a GC-rich 5'-flanking
      region was identified immediately upstream of the transcription start site. These
      minimal promoters were sufficient to generate constitutive activity in CAT
      expression assays. A G-CSF responsive element was mapped within the first 118
      nucleotides upstream of the transcription start site of the IL-8RB gene.
      Expression analyses of additional upstream regions suggested that both IL-8R
      promoters are negatively controlled by silencer elements, which could be
      counteracted by stimulation with G-CSF.

PMID- 8530164
TI  - Differentially regulated expression of human IgG Fc receptor class III genes.
AB  - The expression of the human Fc receptor with low affinity for IgG (Fc gamma RIII,
      CD16) encoded by the Fc gamma RIII-A or Fc gamma RIII-B genes is restricted to
      natural killer (NK), a subset of T cells and macrophages or neutrophils (PMN).
      The genetic heterogeneity of Fc gamma RIII generates alternative membrane
      anchored proteins with distinct signaling capacities when cross-linked by immune
      complexes. Of great importance is the characterization of the regulatory gene
      elements directing the expression of a particular Fc gamma RIII isoform to a
      given specific cell type. Molecular characterization of the Fc gamma RIII-A and
      Fc gamma RIII-B genes has revealed that the promoter regions display distinct
      tissue-specific transcriptional activities. In addition, the differential Fc
      gamma RIII-A/B gene activation can be regulated by enhancer elements located in
      the more upstream and intron regions. Transcription initiation in NK cells occurs
      also outside the normal promoter region by a second independent Fc gamma RIII-A
      promoter. Analysis of the additional Fc gamma RIIIa2-4 transcripts suggests the
      expression of novel, as yet unknown Fc gamma RIII receptor isoforms on NK cells.

PMID- 8530165
TI  - Gene regulation by NF-M and Myb during differentiation and leukemic
      transformation.

PMID- 8530166
TI  - Joint Congress of the British and Netherlands Societies for Immunology. Brighton,
      United Kingdom, 6-8 December 1995. Abstracts.

PMID- 8530167
TI  - Biomaterials and medical implant science.

PMID- 8530168
TI  - Correlative microscopic investigation of the interface between titanium alloy and
      the osteoblast-osteoblast matrix using mineralizing cultures of primary fetal
      bovine mandibular osteoblasts.
AB  - In this study, the primary culture of bovine mandibular osteoblast cells in a
      microculture assay has been used to further investigate the interaction of
      mineralizing osteoblast cultures with implant surfaces by using correlative
      microscopic techniques. Rapid differentiation and mineralization of osteoblast
      cultures grown on titanium alloy surfaces was observed. The successful short-term
      culture of mineralizing mandibular osteoblasts on titanium alloy surfaces
      occurred without the formation of a tenacious adhesive interface between the
      alloplastic material and the multilayered cell culture.

PMID- 8530169
TI  - Osseointegration of titanium implants in bone regenerated in membrane-protected
      defects: a histologic study in the canine mandible.
AB  - In the present histologic study of the mandibles of five foxhounds, 15
      nonsubmerged titanium implants were placed in bone regenerated in extended
      membrane-protected defects during a 6-month healing period. The clinical and
      radiographic evaluation demonstrated that all 15 implants achieved functional
      ankylosis within 3 months following implant placement. Subsequently, eight
      implants were restored with fixed partial dentures and were functionally loaded
      for 6 months, and seven implants were left unrestored. At the completion of the
      study, the histologic analysis demonstrated osseointegration with direct bone-to
      implant contact for all 15 implants. Therefore, it can be concluded that bone
      regenerated in membrane-protected defects responds to implant placement like
      nonregenerated bone, and that this bone is capable of bearing and sustaining
      functional load. The histologic comparison of restored and unrestored sites
      demonstrated no apparent differences concerning bone remodeling activities.
      Furthermore, control sites without implant placement demonstrated bone atrophy
      underneath the membranes with a thin cortical layer and sparse bone trabeculae.
      Thus, it can also be concluded that the placement of an implant into regenerated
      bone stimulated bone maturation and bone remodeling, whereas implant loading did
      not influence bone remodeling in the present study model.

PMID- 8530170
TI  - A modified method of simultaneous bone grafting and placement of endosseous
      implants in the severely atrophic maxilla.
AB  - The purpose of this investigation was to clinically evaluate the modified method
      for surgical rehabilitation of severely atrophied maxillae with titanium
      implants. In 35 patients, sinus lift, Le Fort I osteotomy, and a downtilting of
      the maxilla were performed. Bone grafts from the iliac crest, placed between the
      sinus mucosa and the sinus floor, were secured with three to four Branemark
      titanium implants 10 to 20 mm in length on each side. The osteotomized maxilla
      was stabilized with miniplates. The observation period was between 1 and 4 years
      after abutment connection. The rate of successful osseointegration was 86.6%.

PMID- 8530171
TI  - Identification of axons in the peri-implant region by immunohistochemistry.
AB  - In the edentulous patient with a completely implant-supported prosthesis,
      periodontal ligament receptors are absent. However, the implant patient's
      mandibular function during mastication and clenching is significantly improved
      and can be similar to that of dentulous subjects. The underlying mechanisms that
      govern this proprioceptive control are not well understood. One possibility that
      has been explored only partially is that residual axonal elements in the peri
      implant region may have a proprioceptive function. To survey the peri-implant
      region for axonal elements, this study utilized immunohistochemistry with
      neurofilament as the marker. Histologic sections of the peri-implant area from 12
      implants placed in the mandibles of three dogs were examined for the presence of
      neurofilament. Two to three labeled sites per section in the peri-implant region
      were commonly found. However, the functional significance of these axons must be
      further evaluated before any conclusions regarding their role in proprioception
      can be made.

PMID- 8530172
TI  - Increased interleukin-1 beta in the crevicular fluid of diseased implants.
AB  - Diseased implants can be distinguished from healthy implants by the presence of
      inflammation in the surrounding tissue. Inflammation correlates with elevated
      levels of interleukin-1 beta in gingival crevicular fluid. An analysis of
      interleukin-1 beta levels in diseased implants compared to those in matching
      healthy implants in 12 patients indicates that the level of interleukin-1 beta
      was approximately three times that at healthy sites. Interleukin-1 beta levels
      may provide a means of monitoring the health status of dental implants.

PMID- 8530173
TI  - Single-tooth restorations supported by osseointegrated implants: results and
      experiences from a prospective study after 2 to 3 years.
AB  - Fifty-seven patients were followed for 2 years and 34 patients for 3 years in a
      study of the CeraOne system. One implant was lost, resulting in a cumulative
      success rate of 97.3% at the 3-year examination. All-ceramic crowns were seated
      for 95% of the subjects, and only four of the crowns were classified as failures.
      Two all-ceramic crowns fractured following trauma, but no crown was fractured
      when exposed to common bite forces. The bone loss around implants and adjacent
      teeth was small, and few problems were observed. It was proven that the system
      achieves good esthetic results and avoids the complications of screw loosening
      and fistula formation.

PMID- 8530174
TI  - Evaluation of the clinical predictability of hydroxyapatite-coated endosseous
      dental implants: a review of the literature.
AB  - Although the use of hydroxyapatite-coated (HA-coated) endosseous implants in the
      treatment of dental patients has been established, their clinical predictability
      remains controversial. This study is an analysis of the clinical predictability
      and indications for use of HA-coated endosseous implants. This study also
      discusses the biochemical composition of commercial HA coatings in relation to in
      vivo predictability, potential concerns, and potential advantages of HA coatings.
      Clinical studies suggest that HA-coated implants have short-term survival rates
      (ranging from 6 months to 6 years) that are comparable to short-term survival
      rates of titanium implants. In addition, clinical data suggest that HA-coated
      implants may be valuable treatment modalities when placing implants (1) in type
      IV bone, (2) in fresh extraction sites, (3) in grafted maxillary and/or nasal
      sinuses, or (4) when using shorter implants (less than or equal to 10 mm).
      However, long-term controlled studies are required to validate these
      observations.

PMID- 8530175
TI  - Fibronectin and laminin enhance gingival cell attachment to dental implant
      surfaces in vitro.
AB  - The objective of this study was to determine if the biologically active molecules
      laminin and fibronectin could influence gingival cell attachment to implant
      surfaces in vitro. Flat squares of the following implant materials were tested:
      smooth, plasma-sprayed, and hydroxyapatite-coated titanium. The surfaces were
      coated with equimolar quantities of either laminin, fibronectin, or bovine serum
      albumin. Fibronectin coating of implant surfaces resulted in two to three times
      the enhancement of gingival fibroblast binding on all implant surfaces tested (P
      < .01), with a lesser effect on epithelial cells. Laminin coating resulted in
      three to four times the enhancement of gingival epithelial cell binding on all
      implant surfaces tested (P < .01), with a lesser effect on fibroblasts. The two
      cell types exhibited distinct preferences for the different molecules tested with
      the surface roughness having some influence.

PMID- 8530176
TI  - Mechanical properties of bone-implant interface: an in vitro comparison of the
      parameters at placement and at 3 months.
AB  - Four biomechanical parameters--peak force, vertical displacement, interface
      stiffness, and strain energy--were defined to evaluate bone-implant interface
      properties. These parameters were measured at placement and after 3 months of
      healing during push-in tests on commercially pure titanium implants placed in the
      mandibles of dogs in a one-phase nonsubmerged procedure. Comparison of the
      results showed that peak force, interface stiffness, and strain energy increased
      after 3 months of healing, but vertical displacement decreased. These findings
      suggest that the interface stiffness, which is considered a major factor for
      implant success, increases during 3 months of healing in dogs, which corresponds
      to a 4- to 6-month healing period in human mandibles.

PMID- 8530177
TI  - Direct replacement of failed CP titanium implants with larger-diameter, HA-coated
      Ti-6Al-4V implants: report of five cases.
AB  - Failure to osseointegrate traditionally mandates immediate implant removal,
      followed by a 1-year healing period before placing a second implant into the same
      area. This report presents five cases in which failed screw-type, commercially
      pure titanium implants were immediately replaced by ledge-type, hydroxyapatite
      coated, Ti-6Al-4V implants in the same sockets. These cases suggest that the 1
      year healing period may not be necessary, provided that (1) the socket can be
      reprepared to eliminate thread grooves and invasive soft tissue, (2) the
      replacement implant is larger in diameter than the original implant, and (3)
      sufficient available bone remains for the procedures.

PMID- 8530178
TI  - Overdentures supported by ITI implants: a 6.5-year evaluation of patient
      satisfaction and prosthetic aftercare.
AB  - This study reviews the long-term outcome of overdenture treatment in 64
      completely edentulous patients who received 218 one-stage ITI implants during the
      period 1982 until 1988. The evaluation time averaged a period of 80 months,
      ranging from 66 to 119 months. The results indicate that no implants were lost
      during this period and that a minimum of surgical and prosthetic treatment was
      necessary to maintain the overdentures. Patient satisfaction was high and had not
      significantly changed in comparison with an earlier study on the same group of
      patients after a mean period of 18 months. The assumption that there would be
      significantly more complaints about retention of the maxillary denture is not
      affirmed by this study.

PMID- 8530179
TI  - Health human periodontal versus peri-implant gingival tissues: an
      immunohistochemical differentiation of the extracellular matrix.
AB  - Healthy human periodontal and peri-implant (ITI Bonefit) keratinized gingival
      tissues were studied immunohistochemically to evaluate the possible presence of
      structural differences in the extracellular matrix protein localization. Collagen
      types I, III, IV, and VII and fibronectin showed similar distribution in these
      tissues. Compared to the periodontal tissues, collagen type V was localized in
      higher amounts in the lamina propria of the peri-implant gingival tissues.
      Collagen type VI stained the periodontal tissues as a delicate microfibrillar
      network contrasting to the not well-stained peri-implant gingival tissues. The
      data show that structural differences between these tissues are present. The
      structural differences may be responsible for the defense of peri-implant
      keratinized gingival connective tissues to bacterial penetration, because of the
      high amount of the collagen type V component, which is responsible for the higher
      collagenase stability.

PMID- 8530180
TI  - Treatment of edentulous patients with temporomandibular disorders with implant
      supported overdentures.
AB  - Treatment of edentulous patients who have temporomandibular disorders is
      difficult because of the poor stability of their conventional complete dentures.
      With an implant-supported bar and a clip-to-bar overdenture, mandibular dentures
      can be stabilized. The results of a prospective clinical study of 10 edentulous
      patients with temporomandibular disorders and treatment with implant-supported
      overdentures in mandibles are presented. Before and after 3 years of wearing the
      implant-supported overdentures, patients were interviewed and a clinical
      functional analysis was taken. Patients with displacement of the articular disc
      or bone destruction of the joints had a decrease in pain, an enhanced mobility of
      the mandible, and a decrease in temporomandibular joint sounds. Patients with
      pain of muscular genesis as a result of bruxism suffered after 3 years from the
      same pain and did not show an improvement of muscle or joint sensitivity.

PMID- 8530181
TI  - High-resolution computerized tomography and nuclear bone scanning in the
      diagnosis of postoperative stress fractures of the mandible: a clinical report.
AB  - Root-form titanium dental implants are the treatment of choice for many partially
      and totally edentulous patients. The overall success rate is greater than 95%.
      Postoperative pain is usually the result of infection. This report presents two
      cases involving a sudden onset of jaw pain. Computerized tomographic scanning
      revealed that the pain was caused by stress fracture of the mandible.

PMID- 8530182
TI  - Human retinal microglia: expression of immune markers and relationship to the
      glia limitans.
AB  - The immunoreactivity, morphology and relationship to the glia limitans of
      microglia were investigated in flatmounts and sections of normal human retina,
      using immunogold histochemistry, electron microscopy (EM), and antibodies
      directed against CD45, major histocompatability complex class I (MHC-I), MHC-II,
      and human macrophage antigens. Immunoreactivity was evident for all antibodies
      tested, including MHC-I, which labeled both microglia and retinal vascular
      endothelium. Most consistent labeling was obtained using antibodies to CD45, MHC
      II, and anti-human macrophage (S22) antigen. Immunoreactive cells were seen in
      the perivascular space (perivascular cells), where they were closely adherent to
      the vessel profile, and in the retinal parenchyma (microglia). Some parenchymal
      microglia were also vessel associated and by EM were seen to be closely related
      to the glia limitans (paravascular microglia). Paravascular microglia were shown
      by optical densitometry, to express higher levels of MHC antigens than
      neighboring, non-vessel associated, parenchymal microglia. In addition,
      paravascular microglia were macrophage (S22) antigen positive, while other
      parenchymal microglia did not express macrophage antigens. Quantitative data
      indicate that similar populations of microglia are immunoreactive to CD45, MHC-I,
      and MHC-II, while relatively few microglia (approximately 10%) are immunoreactive
      for human macrophage (S22) antigens, supporting previous suggestions that
      microglia are a heterogeneous population.

PMID- 8530183
TI  - Resident microglia and hematogenous macrophages as phagocytes in adoptively
      transferred experimental autoimmune encephalomyelitis: an investigation using rat
      radiation bone marrow chimeras.
AB  - Hematogenous macrophages are known to be involved in the induction of tissue
      damage in the central nervous system (CNS) as well as of clinical symptoms in
      experimental autoimmune encephalomyelitis (EAE). Although resident microglia can
      become phagocytic under certain circumstances, little is known about the role of
      these cells in brain inflammation in vivo. We thus studied EAE in the model of
      radiation bone marrow chimeras that allows us to distinguish donor-derived
      hematogenous cells from resident effector cells. Inflammation in the CNS was
      qualitatively and quantitatively similar in chimeras compared to fully
      histocompatible Lewis rats. Although activated resident microglial cells were
      outnumbered four- to sevenfold in EAE lesions by hematogenous macrophages, the
      number of resident microglia with ingested myelin was equal to that of
      macrophages containing myelin debris. Phagocytic resident microglia, expressing
      the macrophage activation marker ED1, showed ramified as well as amoeboid
      morphology. From our studies the following conclusions can be drawn. First, a
      considerable proportion of resident microglia upregulated ED1. Second, resident
      microglia provide a small but substantial source of brain macrophages in EAE as
      compared to the large influx of macrophages. Third, our results suggest that
      microglia, due to their strategic position within the CNS, are more effective in
      removal of myelin debris compared to hematogenous macrophages.

PMID- 8530184
TI  - Interleukin 1-beta- and tumor necrosis factor-alpha-mediated regulation of ICAM-1
      gene expression in astrocytes requires protein kinase C activity.
AB  - Several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1)
      are expressed by astrocytes, the predominant glial cell of the central nervous
      system (CNS). Such molecules are important in the trafficking of leukocytes to
      sites of inflammation, and in lymphocyte activation. ICAM-1 is constitutively
      expressed by neonatal rat astrocytes, and expression is enhanced by the
      proinflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor
      alpha (TNF-alpha), and interferon-gamma (IFN-gamma), with IL-1 beta and TNF-alpha
      being the strongest inducers. In this study, we have examined the nature of the
      second messengers involved in ICAM-1 gene expression induced by the cytokines IL
      1 beta and TNF-alpha. Our results indicate that stimuli related to protein kinase
      C (PKC) such as the phorbol ester phorbol 12-myristate 13-acetate (PMA) and
      calcium ionophore A23187 increase ICAM-1 mRNA expression, whereas cyclic
      nucleotide analogs and PKA agonists have no effect. Pharmacologic inhibitors of
      PKC such as H7, H8, and calphostin C inhibit ICAM-1 gene expression inducible by
      IL-1 beta and TNF-alpha. Prolonged treatment of astrocytes with PMA results in a
      time-dependent downregulation of the PKC isoforms alpha, delta, and epsilon, and
      a concomitant diminution of ICAM-1 mRNA expression induced by IL-1 beta, TNF
      alpha, and PMA itself at specific time points post-PMA treatment. These data,
      collectively, demonstrate a role for various PKC isoforms in IL-1 beta and TNF
      alpha enhancement of ICAM-1 gene expression in rat astrocytes.

PMID- 8530185
TI  - Astrocytic gap junction removal, connexin43 redistribution, and epitope masking
      at excitatory amino acid lesion sites in rat brain.
AB  - We previously reported that kainic acid (KA) lesion sites in rat brain exhibit an
      absence of astrocytic gap junctions at 1 week post-lesion. Loss of
      immunocytochemical reactivity with a sequence-specific antibody against the
      astrocytic gap junctional protein connexin43 (Cx43) suggested epitope masking
      since persistence of Cx43 was observed on Western blots. Here, we determined the
      fate of Cx43 at various times after thalamic KA and striatal NMDA lesions. In
      normal tissue and at 6 hr post-KA lesion, Cx43 immunoreactivity predominated at
      typical astrocytic gap junctions. Immunolabelled junctions were still seen at 3
      days, with epitope masking already present, and were virtually absent by 6 days
      post-lesion. Gap junction remodeling was indicated by the appearance of
      intracellular immunostained annular profiles and uncharacteristically extensive
      gap junctions between symmetrically immunolabelled membranes and between labelled
      astrocytic and unlabelled oligodendrocytic membranes. Labelled multivesicular
      clusters emerged at 2 days, were numerous at 3 days and constituted the sole Cx43
      sequestration site by post-lesion day 6. Ultrastructural disruption and gap
      junction disassembly progressed more slowly in NMDA-injected tissue where
      immunoreactivity persisted, albeit at markedly decreasing levels until the final
      survival time examined (16 days). Intense Cx43 immunolabelling was seen in
      filopodia of putative reactive astrocytes at the lesion periphery at 6-8 days and
      was associated at 16 days with an increased number of gap junctions primarily
      between fine astrocytic processes. These results demonstrate that massive
      neuronal loss alone or in conjunction with direct actions of excitotoxins on
      astrocytes precipitates an astrocytic reaction accompanied initially by removal
      of their gap junctions followed by redistribution of Cx43, and suggest that the
      astrocytic syncytium may undergo reorganization in a manner leading to isolation
      of the lesion site.

PMID- 8530186
TI  - Molecular cloning of IL-2R alpha, IL-2R beta, and IL-2R gamma cDNAs from a human
      oligodendroglioma cell line: presence of IL-2R mRNAs in the human central nervous
      system.
AB  - In the present study, we analyzed human adult brain, fetal spinal cord, and an
      interleukin-2 (IL-2)-responsive human oligodendroglioma subclone, TC620.6A2, for
      the presence of mRNAs for the alpha, beta, and gamma chains of the interleukin-2
      receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma). IL-2R beta mRNA, but not IL
      2R alpha or IL-2R gamma was detectable by Northern blot analysis in adult human
      brain tissues. Northern blot analysis of TC620.6A2 and human fetal tissues
      revealed mRNAs of 1.5 kb and 1.3 kb that hybridized to the IL-2R alpha cDNA at
      low to medium stringency. Reverse transcriptase-polymerase chain reaction (RT
      PCR) experiments were done on the TC620.6A2 cell line utilizing primers to IL-2R
      alpha, IL-2R beta, and IL-2R gamma. Southern blot analysis of the TC620.6A2 RT
      PCR reactions detected products identical in size to the peripheral blood
      lymphocyte (PBL) positive controls at high stringency. Several of the TC620.6A2
      IL-2R alpha, IL-2R beta, and IL-2R gamma cDNAs were cloned and sequenced. The
      sequences were found to be identical to the known IL-2R sequences. To our
      knowledge, these experiments are the first to demonstrate the presence of
      authentic IL-2R mRNAs in a human oligodendrocyte-like cell line. Demonstration of
      mRNA for IL-2R beta in human adult brain, IL-2R alpha in fetal brain, and IL-2R
      alpha, IL-2R beta, and IL-2R gamma in a malignant neural cell line suggests the
      possibility of a role for IL-2/IL-2R interactions in development and disease.

PMID- 8530187
TI  - Expression of myelin transcription factor I (MyTI), a "zinc-finger" DNA-binding
      protein, in developing oligodendrocytes.
AB  - The production of myelin by oligodendrocytes requires the coordinated, massive
      synthesis of myelin components, a program that is dependent on transcriptional
      controls. Myelin transcription factor I (MyTI) was named for its ability to
      recognize the proteolipid protein (PLP) gene, the most abundantly transcribed
      central nervous system myelin gene (Kim and Hudson: Mol. Cell Biol. 12:5632,
      1992). MyTI is a zinc-dependent, DNA-binding protein of the Cys2-His-Cys class.
      The pattern of MyTI expression, documented in the present study, suggests that
      MyTI may be instrumental in early stages of oligodendrocytic development and
      myelin production. MyTI mRNA transcripts are more highly expressed in
      oligodendrocyte progenitors than in differentiated oligodendrocytes. In vitro and
      in vivo analyses show that MyTI immunoreactivity is stronger in oligodendrocytic
      progenitors than in mature oligodendrocytes which have already accumulated PLP.
      In oligodendrocyte progenitors, MyTI immunoreactivity appears as speckles within
      the nucleus, suggestive of an association of MyTI with a function that is
      spatially segregated into discrete nuclear domains. MyTI continues to be
      expressed in cells transcribing PLP. However, as oligodendrocytes accumulate PLP,
      MyTI immunoreactivity becomes restricted to the cytoplasm and progressively
      diminishes. Since MyTI has two widely separated sets of DNA-binding domains and
      initial MyTI expression markedly precedes PLP expression, we hypothesize the
      following model: MyTI may play a role in assembling transcriptionally active
      complexes of PLP, perhaps by bending the DNA of the promoter region to induce an
      appropriate conformation to enable subsequent binding of additional regulatory
      proteins.

PMID- 8530188
TI  - Three different thyroid hormone receptor isoforms are detected in a pure culture
      of ovine oligodendrocytes.
AB  - Thyroid hormones are important for the normal development of the central nervous
      system. In humans, the period around the end of the intrauterine life and the
      first few months of neonatal life is critically dependent on the presence of
      normal amounts of thyroid hormone. There are significant events occurring during
      this time; myelination is one. Myelin is synthesized by oligodendrocytes. A panel
      of site-specific polyclonal antibodies against alpha-1 thyroid hormone receptor
      (TR), alpha-2 variant TR, and beta-1 TR isoforms has been employed to investigate
      the presence of TR isoforms in a pure culture of ovine oligodendrocytes by the
      avidin-biotin peroxidase immunocytochemical method. Strong nuclear staining was
      obtained with all the anti-TR antibodies; no reaction products were detected in
      the cytoplasm or cellular processes. By contrast, an anti-myelin basic protein
      antibody gave strong cytoplasmic and process staining; no nuclear staining was
      seen. These latter results served to 1) confirm that the cells under study are
      oligodendrocytes; and 2) prove that the nuclear staining with anti-TR antibodies
      is specific. Preimmune sera were totally negative. Scatchard analysis of [125I]
      T3 binding by isolated oligodendrocyte nuclei demonstrated the existence of high
      affinity--low-capacity T3 binding sites with a Ka of approximately 6 x 10(-9) M
      and a maximal binding capacity of approximately 20 fmol/100 micrograms of DNA.
      Our results demonstrate that differentiated oligodendrocytes express alpha-1 and
      alpha-2 variant and beta-1 isoforms of TR at the protein level and support the
      notion of a direct impact of thyroid hormones on oligodendrocytes in their
      regulation of myelin synthesis.

PMID- 8530189
TI  - Remembrances of Amico Bignami.

PMID- 8530190
TI  - Age and skilled psychomotor performance: a comparison of younger and older
      golfers.
AB  - Younger golfers (mean age 33.6 years) and older golfers (mean age 62.3 years) who
      were equivalent at a molar level of performance (shots taken per round of golf)
      were compared through componential analysis in order to identify age differences
      in psychomotor skills. Consistent with an age-related decline in physical
      strength, older golfers drove the ball a shorter distance from the tee than
      younger golfers. They also adopted a more conservative approach to shotmaking
      when playing golf and reported experiencing fewer negative emotions and
      cognitions in relation to performance. Such differences suggest that age-related
      impairment in some component skills are, at least in the case of some
      individuals, compensated for by greater reliance on skills that either improve or
      remain stable with age. Directions for further study of compensatory adjustment
      are noted.

PMID- 8530191
TI  - Affective responses to acute exercise in elderly impaired males: the moderating
      effects of self-efficacy and age.
AB  - The purpose of the present study was to examine the relationships between
      perceptions of personal efficacy and affective responsibility to acute exercise
      in elderly male in-patients and outpatients at a Veterans Administration Medical
      Center. Participants completed self-efficacy measures prior to and following
      upper body ergometry exercise. Multidimensional affect was assessed prior to and
      following activity and in-task affect was assessed by retrospective recall. A
      significant change in feelings of fatigue was revealed over time but exercise
      effects on affect were shown to be moderated by perceptions of efficacy and age.
      Specifically, more efficacious individuals reported significantly more positive
      well-being and less psychological distress during and following exercise. Older
      individuals were less efficacious and experienced more negative responses to
      exercise. Finally, participants who experienced less psychological distress and
      more positive well-being during activity were more efficacious post-exercise. The
      results are discussed with respect to the role played by self-efficacy and age in
      the generation of affective responses to exercise.

PMID- 8530192
TI  - Dimensions and progression in the interaction between bilingual/monolingual
      caregivers and bilingual demented immigrants: analysis of video-recorded morning
      care sessions in institutions coded by means of the Erikson theory of "eight
      stages of man".
AB  - Seven demented Finnish immigrants were video-recorded during morning care
      together with bilingual and monolingual Swedish-speaking caregivers. A
      phenomenological-hermeneutic analysis of the video-recordings inspired by
      Ricoeur's philosophy was performed. The structural analysis was made by means of
      the Erikson theory of "eight stages of man." A statistical analysis was done in
      order to study dimensions and progression of interaction and compare the
      communication seen in relation to how caregivers supported the patients'
      integrity.

PMID- 8530193
TI  - The experience of being at home throughout the life span. Investigation of
      persons aged from 2 to 102.
AB  - One hundred and fifty persons aged two to 102 narrated their experiences related
      to the phenomenon "being at home." Several common interdependent and interrelated
      aspects of the experience of being at home were identified throughout the life
      span. These aspects are believed to entail cognitive, emotional, and conative
      dimensions of the experience: safety, rootedness, harmony, joy, privacy,
      togetherness, recognition, order, control, possession, nourishment, initiative,
      power, freedom. The sense of being related was found to be a common condition of
      the experience of being at home, i.e., related to significant others, significant
      things, significant places, significant activities, oneself, and transcendence.
      In the process of maintaining the experience of being at home throughout life the
      phenomena "being given a home," "creating a home," "sharing a home," and
      "offering a home" were integral parts. A progression in the experience of being
      at home throughout the life span was identified.

PMID- 8530194
TI  - Friends in passing: social interaction at an adult day care center.
AB  - This study explores the social interactions and friendships that exist among
      cognitively impaired adult day care participants. A five month participant
      observation of an adult day care center was conducted, involving fifty-three
      clients ranging in age from sixty-six to ninety-three. Findings indicate that the
      clients engage in a variety of social interactions and friendships, enabling them
      to maintain a sense of self as well as to adjust to the norms of the group.
      Specific areas to be discussed are: general socializing, enduring friendships,
      helping relationships and client integration. A descriptive approach such as this
      provides the opportunity to examine the complexity of social interactions,
      including the positive relationships available to the cognitively impaired
      elderly.

PMID- 8530195
TI  - Aging and encoding in memory: false alarms and decision criteria in a word-pair
      recognition task.
AB  - Employing a false alarm recognition procedure with learning of highly associated
      word pairs, an experiment was conducted to examine the hypothesis of an age
      related deficit in the distinctiveness of encoding. The evolution of the false
      alarm rate and of the C decision criteria was observed across three age groups,
      young adults, older adults, and older-older adults. The results show 1) no age
      differences on C decision criteria, indicating that the increase in FA with age
      is not related to a subject compensation strategy but is probably due to a
      failure in memory strength, and 2) that older respondents produced significantly
      more false alarms to distractors related to target items than the young
      respondents did but that they did not differ in their false alarm rate for
      unrelated distractors. This finding is interpreted as supporting the hypothesis
      of a failure with age to encode target items in a sufficiently elaborate or
      distinctive fashion. For the older-older respondents the data showed an increase
      in all false alarms indexes, suggesting that the encoding deficit gets worse in
      late adulthood.

PMID- 8530196
TI  - Insulin injectors: a practical approach to insulin therapy.

PMID- 8530197
TI  - Factors affecting nPCR in hemodialysed patients.
AB  - The determination of dialysis adequacy is difficult and definitions are in a
      state of flux (Lindsay). In fact, after fifteen years from the introduction of
      urea kinetics into clinical practice, nephrologists still do not agree on
      recognizing the real utility of it. Gotch and Sargent in their mechanistic
      analysis of the NCDS indicated that the dose of small molecules removal could be
      defined by Kt/V urea. The results of the NCDS were depicted in a three-variable
      plot in which six domains could be seen. Several reports have documented
      malnutrition as being frequently present in patients on maintenance hemodialysis.
      It is generally accepted that a suboptimal nutritional status is associated with
      an increased morbidity and may adversely affect rehabilitation and the quality of
      life. In 1989 Lindsay et al showed that low levels of Kt/V corresponded with low
      levels of nPCR and found a direct correlation between the two parameters. On this
      basis, they suggested the hypothesis of nPCR dependence on Kt/V. The Authors
      showed a good correlation (r = 0.73) between nPCR and Kt/V in 55 patients. This
      work aims to evaluate the correlation between Kt/V and nPCR, real age and
      dialytic age in a dialytic population in Southern Italy, during a long period of
      observation (six years, follow up 2,692 months). One hundred and thirty-four
      patients were studied in six years of observation. Follow up: 2,692 months.
      Twenty-six patients died during the observation period. The simple regression
      analysis of nPCR vs. Kt/V, real age and dialytic age was performed in 63 anuric
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8530198
TI  - Can the artificial heart make the circulation become fractal?
AB  - In order to analyze the hemodynamic parameters in prosthetic circulation as an
      entity and not as decomposed parts, non linear mathematical analyzing techniques,
      including the fractal dimension analyzing theory, were utilized. Two
      pneumatically actuated ventricular assist devices were implanted, as
      biventricular bypasses (BVB), in chronic animal experiments, using four healthy
      adult goats. For the comparison between the natural and prosthetic circulation in
      the same animals, the BVB type complete prosthetic circulation model with
      ventricular fibrillation, was adopted. All hemodynamic parameters with natural
      and prosthetic circulation were recorded under awake conditions, and calculated
      with a personal computer system. Using the non-linear mathematical technique, the
      arterial blood pressure waveform was embedded into the return map as the beat-to
      beat time series data and fractal dimension analysis were performed to analyze
      the reconstructed attractor. By the use of the Box counting method, fractal
      dimension analysis of the hemodynamics was performed. Return map of the
      hemodynamics during natural and artificial circulation showed fractal
      characteristics, and fractal dimension analysis of the arterial blood pressure
      revealed the fact that lower dimensional fractal dynamics were evident during
      prosthetic circulation. Fractal time series data is suggested to have robustness
      and error resistance, thus our results suggest that the circulatory regulatory
      system with an artificial heart may have these desired characteristics.

PMID- 8530199
TI  - Evaluation of cryopreserved arteries as alternative small vessel prostheses.
AB  - Biologic or synthetic grafts have had limited success in small vessel
      applications. Studies were initiated to assess the potential use of cryopreserved
      (CP) arteries as coronary artery bypass conduits. Sheep carotid arteries
      (internal diameter: 4 mm; length: 10 cm) were cryopreserved in a nutrient media
      containing 10% DMSO and were stored in a nitrogen vapor at -150 degrees C. After
      thawing, histological, enzyme-histochemical and functional studies showed slight
      histological alterations, preservation of enzymal activities and an abolition of
      the contractile response. In a sheep model, arterial substitution of a 10 cm
      segment of carotid artery was realised by implantation of fresh autografts ( n =
      4); fresh allografts (n = 9) and CP allografts (n = 9). After 3 months, all
      autografts were patent with slight histological alterations. Fresh and CP
      allografts showed similar modifications: patency rate was 7/9 in both groups.
      Intimal thickening with cell proliferation was seen in fresh (3/7) and CP (4/8)
      arteries; loss of smooth muscle medial cells was constant. Adventitia was always
      involved by a marked inflammatory reaction. One characteristic of CP allografts
      was the frequent presence of large dystrophic calcifications. In conclusion,
      morphologic and functional arterial changes occurred after freezing and thawing.
      In spite of vascular rejection, the patency rate of allografts after 3 months of
      implantation in arterial circulation remained high and does not seem influenced
      by cryopreservation.

PMID- 8530200
TI  - Elastomeric valves, a new design.
AB  - The convex bileaflet valve replaces the flat biflap inflow valve designed by Long
      Sheng Yu and the tricusp semilunair outflow valve. One reason is easier
      manufacturing. Convex bileaflet valves are developed for the 11, 20, 40, 70 and
      140cc ventricles. Testing included curves (Cardiac Output versus Venous Pressure,
      Cardiac Output versus Heart rate), flow visualization studies, paint and bloodbag
      studies. The curves and flow visualization were done by connecting ventricles to
      one of our standard mock circulations. Paint and bloodbag studies were done by
      connecting the hearts to a bloodbag, but the bag was filled with water for the
      paint studies. The curves show high cardiac output, even with pumping at high
      heart rates (150 BPM+). The flow visualization shows a good stream through the
      sinus Valsalvae. No stagnating flow is visible. The bloodbag studies which
      provoke thrombosis show it on the edges of the heart valves, and little in the
      groove between the valve and the sinus Valsalvae. Heparninzation prevents the
      thrombosis. Results of our tests were good. The convex bileaflet valve seems to
      have good future.

PMID- 8530201
TI  - Efficacy of lipid apheresis: definitions and influencing factors.
AB  - The comparison of efficiency of currently available lipid apheresis systems has
      been hampered by different definitions of efficacy and poorly controlled
      apheresis conditions. This paper suggests definitions of efficacy and
      standardization of its determinants. The acute efficacy of risk factor reduction
      reflects the relative decrease of pathogen by a single treatment session compared
      to preapheresis levels. Standardization of treated plasma volume in relation to
      the patients plasma volume and correction of changes in plasma volume during the
      procedure are mandatory. Its determination is most useful in the technical
      evaluation of new systems. The long-term efficacy of risk factor reduction as
      compared to baseline is determined by mean interapheresis levels of e.g. LDL-C in
      the pseudo-steady-state after about 3 months of regular treatment. It is the
      major criterion for potential regression of coronary artery disease and absolute
      average plasma levels of 120 < or = mg/dl LDL-C should be attained. It is
      influenced by the acute efficacy of the system, apheresis frequency and rebound
      kinetics. The clinical efficacy is defined by apheresis induced reduction of
      coronary morbidity and mortality. It is influenced by long-term risk factor
      reduction, the selectivity of the system as well as the control of non-lipid risk
      factors. Apheresis related effects on coronary artery disease comprise functional
      improvements of hemorheology and vasomotion as well as morphological benefits
      like regression of luminal narrowing and plaque stabilization.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8530202
TI  - Therapeutic use of albumin.
AB  - The clinical use of albumin solutions is a controversial issue, that involves
      albumin as a volume plasma expander, a supplement of total parenteral nutrition
      and a substance with pharmacological properties. The aim of this review is to
      show the present role of albumin in the clinical setting. We reviewed
      experimental and clinical data collected by the Medline System and the
      bibliographies of relevant articles. Experimental studies were selected on the
      basis of their historical value and applicability (hypothetical use, correct use)
      to the clinical setting. At present, it is possible to assert that: a) exogenous
      albumin is not an ideal colloid; b) the effects on plasma volume expansion are
      not entirely predictable, especially in pathologic states accompanied by leaky
      capillary membranes; c) albumin supplementation shows no benefit on many kinds of
      tissue edema; d) the supplementation of albumin has no influence on outcome. It
      is possible to demonstrate the role of albumin as a substance with unique
      properties that make it useful, but further experimental and clinical data will
      be necessary and represent new areas for future exploration. Given the protein's
      cost, the routine use of albumin does not appear to be justified, until new data
      indicate otherwise.

PMID- 8530203
TI  - Biological and synthetic conduits in peripheral nerve repair: a comparative
      experimental study.
AB  - Two different types of conduits, one biological, obtained with homologous
      glutaraldehyde preserved vein segments and the other synthetic bioabsorbable,
      made with Poly [L-lactide-co-6-caprolactone], were evaluated as guides for nerve
      repair in alternative to autologous grafts in an experimental animal model. Under
      general anesthetic, the ischiatic nerve of a number Wistar rats was transected to
      create a 1 cm gap, which was then repaired by means of the conduits or autologous
      grafts. Controls were performed at 1, 3 and 6 months; nerve regeneration was
      effective with both conduits, but the count of myelinated axons showed a
      significant difference between the synthetic and biological tubes (p < 0.001).
      The Poly [L-lactide-co-6-caprolactone] guide was still intact 30 days after
      implant; progressive signs of degradation were present at 90 and 180 days. These
      results show that the synthetic conduits are better than those obtained with
      preserved vein segments and might be considered in alternative to autologous
      grafts in peripheral nerve reconstruction.

PMID- 8530204
TI  - Our experience with acetate-free biofiltration.

PMID- 8530206
TI  - Environmental impact on crew of armoured vehicles: effects of 24 h combat
      exercise in a hot desert.
AB  - A field study was undertaken to investigate the effects of combined noise,
      vibration and heat stress on the physiological functions of the crew of armoured
      vehicles during prolonged combat exercise in a desert. The sound pressure level
      of noise was measured with a sound level meter and accelerations by vibration
      analyser. The thermal load on the crew was evaluated by calculating the wet bulb
      globe temperature index. The physiological responses of the subjects (n = 9),
      included significant increases in the heart rate, 24 h water intake and urinary
      catecholamine concentration. A significant decrease was recorded in body mass,
      peak expiratory flow rate and 24 h urinary output. The high heat load on the crew
      resulted in a hypohydration of 3% body mass and appeared to be the dominant
      factor in producing the physiological strain.

PMID- 8530205
TI  - Solar activity cycle and the incidence of foetal chromosome abnormalities
      detected at prenatal diagnosis.
AB  - We studied 2001 foetuses during the period of minimal solar activity of solar
      cycle 21 and 2265 foetuses during the period of maximal solar activity of solar
      cycle 22, in all women aged 37 years and over who underwent free prenatal
      diagnosis in four hospitals in the greater Tel Aviv area. There were no
      significant differences in the total incidence of chromosomal abnormalities or of
      trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%,
      respectively). However, the trend of excessive incidence of chromosomal
      abnormalities in the period of maximal solar activity suggests that a prospective
      study in a large population would be required to rule out any possible effect of
      extreme solar activity.

PMID- 8530207
TI  - Circadian and seasonal variation of the body temperature of sheep in a tropical
      environment.
AB  - Nychthemeral and annual rhythms of the rectal temperature were determined for
      Corriedale sheep in a tropical climate. The minimum rectal temperature averaged
      39.55 degrees C at 0500 hours in summer, and 38.87 degrees C at 0600 hours in
      winter. The maximum was 40.03 degrees C in summer (1700 hours) and 39.33 degrees
      C in winter (1830 hours). Annual cycle of the rectal temperature showed a minimum
      in July and maximum in December.

PMID- 8530208
TI  - A year-round study on functional relationships of airborne fungi with
      meteorological factors.
AB  - Air sampling was conducted in Waterloo, Canada throughout 1992. Functional
      relationships between aeromycota and meteorological factors were analysed. The
      meteorological factors were, in descending order of importance: mean temperature,
      minimum temperature, maximum temperature, mean wind speed, relative humidity
      (RH), rain, maximum wind speed and snow. The most important airborne fungal
      propagules in descending order were total fungal spores, unidentified
      Ascomycetes, Cladosporium, Coprinus, unidentified Basidiomycetes, Alternaria and
      unidentified fungi. Most airborne fungal taxa and highly significant relationship
      with temperature, but Aspergillus/Penicillium, hyphal fragments were positively
      associated with wind speed. In comparison with other airborne fungal taxa,
      Leptosphaeria and unidentified Ascomycetes were more closely correlated with rain
      and RH during the growing season.

PMID- 8530209
TI  - Climate change and the incidence of food poisoning in England and Wales.
AB  - In recent years there have been several spells of high temperatures providing
      analogues for the conditions that might become more common as a result of the
      enhanced greenhouse effect. Statistical models were developed of the relationship
      between the monthly incidence of food poisoning and temperatures and these were
      then used to provide estimates of the possible effects of future warmer summers.
      Routinely collected data on the number of reported cases of food poisoning were
      analysed for the years 1982-1991. Regression analysis was used to establish the
      relationship between the monthly of food poisoning and temperatures of the same
      and the previous month. Published scenarios for future temperatures were applied
      to these statistical models to provide estimates of the possible impacts of
      warmer conditions. The monthly incidence of food poisoning was found to be
      significantly associated with the temperature of the same and of the previous
      month with the latter having the stronger effect. Using published data on the
      relationship between reported and actual numbers of cases of food poisoning, it
      is estimated that annually there might be an additional 179 000 cases of food
      poisoning by the year 2050 as a result of climate change. The observed
      relationship with the same month's temperature underlies the need for
      improvements in storage, preparation and hygiene close to the point of
      consumption. However, there was a much stronger relationship with the temperature
      of the previous month, indicating the importance of conditions earlier in the
      food production process. Improvements in areas such as animal husbandry and
      slaughtering may also be necessary to avoid the adverse effects of a warmer
      climate.

PMID- 8530210
TI  - Predicting survival time for cold exposure.
AB  - The prediction of survival time (ST) for cold exposure is speculative as reliable
      controlled data of deep hypothermia are unavailable. At best, guidance can be
      obtained from case histories of accidental exposure. This study describes the
      development of a mathematical model for the prediction of ST under sedentary
      conditions in the cold. The model is based on steady-state heat conduction in a
      single cylinder comprised of a core and two concentric annular shells
      representing the fat plus skin and the clothing plus still boundary layer,
      respectively. The ambient condition can be either air or water; the distinction
      is made by assigning different values of insulation to the still boundary layer.
      Metabolic heat production (M) is comprised of resting and shivering components
      with the latter predicted by temperature signals from the core and skin. Where
      the cold expousure is too severe for M to balance heat loss, ST is largely
      determined by the rate of heat loss from the body. Where a balance occurs, ST is
      govedrned by the endurance time for shivering. End of survival is marked by the
      deep core temperature reacing a value of 30 degrees C. Th emodel was calibrated
      against survival data of cold water (0 to 20 degrees C) immersion and then
      applied to cold air exposure. A sampling of ST predictions for the nude exposure
      of an average healthy male in relatively calm air (1 km/h wind speed) are the
      following: 1.8, 2.5, 4.1, 9.0, and > 24 h for -30, -20, -10, 0 and 10 degrees C,
      respectively. With two layers of loose clothing (average thickness of 1 mm each)
      in a 5 km/h wind, STs are 4.0, 5.6, 8.6, 15.4, and > 24 h for -50, -40, -30, -20,
      and -10 degrees C. The predicted STS must be weighted against the extrapolative
      nature of the model. At present, it would be prudent to use the predictions in a
      relative sense, that is, to compare or rank-order predicted STs for various
      combinations of ambient conditions and clothing protection.

PMID- 8530211
TI  - Substance involvement among juvenile murderers: comparisons with older offenders
      based on interviews with prison inmates.
AB  - We evaluated substance involvement among incarcerated juvenile offenders
      convicted of murder of manslaughter. Patterns of substance involvement among
      juvenile offenders were compared with patterns found in older offenders.
      Irrespective of age group, close to one-third of all homicide perpetrators
      reported that they were affected by alcohol prior to the offense. In every age
      group, alcohol was the substance showing the highest rate of "regular" lifetime
      use and the highest rate of ingestion in the week preceding the homicide. In many
      respects, the reported substance use patterns in the 16-17-year-old age group
      were closer to the patterns demonstrated by the oldest (36+) age group than they
      were to the adjacent 18-20-year-old group. Juvenile offenders were generally less
      substance involved than all but the oldest group of offenders. Almost all of the
      juveniles who were substance involved prior to the homicide attributed the
      homicide to the effects of those substances. Narrative accounts suggest that
      substances (almost always alcohol) escalated impulsive, spontaneous violent
      outbursts. Implications for the interpretation of self-reports about substance
      use provided by murderers are also discussed.

PMID- 8530212
TI  - Drug progression model: a social control test.
AB  - A social control drug progression model was delineated and tested using a sample
      of 2,626 high school students from the southwestern United States. Along with the
      social control constructs of parental attachment, educational attachment,
      religious attachment, and conventional values, we incorporated alcohol,
      cigarette, and marijuana use into the model as intervening variables. The model
      explains 39% of the variation in the self-reported amphetamine use and 24% of the
      variation in "hard drug" use (cocaine, heroin, LSD, and PCP). The findings
      suggest that the integration of social control theory and drug progression
      improves the predictive power of the model of adolescent drug use.

PMID- 8530213
TI  - The influence of family, school, and peers on adolescent drug misuse.
AB  - The socializing impact of the family is compared to that of peers during
      adolescent progressive involvement with drugs. This longitudinal study replicates
      in the school population of Madrid the work of Kandel and associates in the state
      of New York in an attempt to verify the "stepping-stone" hypothesis. Although the
      Madrid study detected a sequence of drug use similar to that in the New York
      study, the Spanish study hypothesized tobacco use to be the first stage and
      alcohol use the second. Cultural traits explain the different findings of these
      studies, especially those concerning the preventive role of the mother-child bond
      among Spanish adolescents.

PMID- 8530214
TI  - Predictors of recidivism to a juvenile assessment center.
AB  - We report the results of a study of the predictors of recidivism to a Juvenile
      Assessment Center in Hillsborough County, Florida, involving over 2,000 youths
      processed at the center during its first 8 months of operation. Consistent with
      previous research, younger aged youths, youths with abuse or neglect histories,
      with previous arrests for property, violence, or drug offenses, with potential
      vocational, leisure-recreation, and family problems, or who were arrested on
      property felony charges were likely to recidivate. The program activity and
      policy implications of these results are discussed.

PMID- 8530215
TI  - Is there a relationship between "heavy drinking" and HIV high risk sexual
      behaviors among general population subjects?
AB  - The authors investigated the association between "heavy drinking" and sexual
      behaviors among 2,581 general population subjects from the St. Louis
      Epidemiologic Catchment Area survey conducted from 1981 to 1983. Lifetime sexual
      behaviors included promiscuity, infidelity, receiving money for sex, and same
      gender sex. It was found that sexual behaviors were associated with lifetime
      heavy drinking. Regardless of gender, race, or age, "heavy drinkers" were
      significantly more likely to report each of the high risk sexual behaviors,
      except same gender sex, compared to "nonheavy drinkers." With the multiple
      logistic regression analyses it was found that "heavy drinking" non-Black
      females, Black males regardless of drinking history, "heavy drinking" males, and
      younger subjects regardless of drinking history were at higher risk to report the
      high risk sexual behaviors. This study confirms that there is a strong
      association between "heavy drinking" and high risk sexual behaviors in a
      midwestern population. This is the first study to find an association between
      alcohol drinking patterns and high risk sexual behaviors in the general
      population. Implications of these findings for public health education efforts
      are discussed.

PMID- 8530216
TI  - Genetics and primary prevention of drug and alcohol abuse.

PMID- 8530217
TI  - Smoking patterns and cessation motivations during adolescence.
AB  - With increased knowledge of effective prevention of adolescent smoking, there is
      a concomitant lack of research on effective adolescent smoking cessation. This
      study surveyed 77 adolescents (mean age 15.8 years) at a youth detention center
      in Seattle, Washington, about smoking patterns, cessation attempts, and
      motivations as well as withdrawal symptoms from nicotine. The results revealed
      that the majority of smokers had previously attempted smoking cessation (72%).
      The most common reasons for wanting to quit were for health concerns. Only 30.8%
      abstained for more than 1 month, and 35.9% abstained for less than 3 days.
      Nicotine craving was the most severe and most commonly reported withdrawal
      symptom.

PMID- 8530218
TI  - Reasons for abstinence among Moslem, Druze, and Christian adolescents in Israel.
AB  - This article describes reasons for abstinence of 1,066 Israeli Arab (Moslem,
      Druze, and Christian) adolescents in the north of Israel in winter 1994. It
      analyzes the results by religious group, gender, and location. "Alcohol damages
      health" and "Do not like the taste/smell" are the most prevalent reasons for not
      drinking among Christians. "Alcohol damages health" and "Religion intolerant of
      alcohol use" are most important among Moslems and Druze. "Do not care for it" and
      "Have seen bad examples of what alcohol can do" are also prominent reasons among
      Arab respondents. Implications of results for prevention are included.

PMID- 8530219
TI  - Smoking cessation leads to reduced stress, but why?
AB  - Recent longitudinal studies have demonstrated that smoking cessation leads to
      reduced feelings of stress. This finding is not predicted by either of the two
      main models for smoking behavior. The nicotine resource model (Warburton) states
      that nicotine is used to cope with external stressors, and predicts that smokers
      will suffer from increased stress when they quit smoking. The deprivation
      reversal model (Schachter), suggests that smoking reverses the deleterious
      effects of deprivation; cessation will then lead to a period of increased stress,
      followed by a return to baseline. Although the stress/cessation data agree with
      neither model, they are consistent with a third explanation, namely that smoking
      causes stress. This model states that acute nicotine deprivation (i.e., between
      cigarettes) leads to increased stress. Smokers then use cigarettes to reverse
      these withdrawal effects and "normalize" their mood. This model explains some
      paradoxical aspects of the smoking/mood relationship. First, why smokers are
      calmed by smoking, yet report high average levels of stress. Second, why stress
      levels become reduced after smoking cessation; this is because the former smoker
      no longer suffers from the adverse mood effects of acute nicotine depletion.

PMID- 8530220
TI  - Laparoscopic cholecystectomy: the Dammam Central Hospital experience.
AB  - Over a one year period (June 1992-June 1993), 260 patients (208 females and 52
      males) with mean age of 37 years (range 13-80), underwent laparoscopic
      cholecystectomy (LC) for symptomatic gallstones. Thirty patients were admitted as
      emergency (20 acute cholecystitis, 10 acute pancreatitis). The procedure was
      performed successfully in 232 cases (89%). In 28 patients (18 electives, 10
      emergencies), the procedure was converted to open for a variety of reasons,
      difficult anatomy being the commonest. Our mean operative time was 99.9 minutes
      (range 30-290 minutes). There were 3 major complications (2 common bile duct
      injuries and one abdominal aortic injury) and 4 minor complications (2 wound
      infections, one prolonged ileus and one chest infection). There was one death due
      to sickle cell crisis on the fifth post-operative day. The mean hospital stay was
      2.3 days and 6.5 days for LC and converted cases, respectively. Our results
      suggest that laparoscopic cholecystectomy can be offered and conducted safely and
      effectively in the great majority of patients presenting acutely or electively
      with cholelithiasis, and that the results we achieved during the first year of
      our experience with LC is comparable to those reported from Europe and North
      America.

PMID- 8530221
TI  - Ultrasonic dissection in resection of hepatocellular carcinoma.
AB  - An ultrasonic dissector has been used in the resection of liver tumors and was
      found to be safe and efficient in noncirrhotic patients. Thirty-one (cirrhosis,
      61%) liver resections for hepatoma treated with ultrasonic dissector were
      compared to 39 (cirrhosis, 74%) resections treated with finger fracture. We found
      that patients treated with an ultrasonic dissector versus those treated by finger
      fracture, had less blood loss (especially in cirrhotic liver), 836 +/- 593 cc vs
      1348 +/- 1226 cc, more operative time, 337.6 +/- 100.5 min vs 197 +/- 92.8 min,
      more days of hospital stay 19.1 +/- 12.8 days vs 11.5 +/- 5.6 days and more days
      of removal of drains, 14.9 +/- 11.7 days vs 10.2 +/- 6.4 days. The morbidity,
      mortality, amount of blood transfusion and amount of drainage were quite similar
      between two groups.

PMID- 8530222
TI  - Tolerance of chronically-diseased liver to prolonged hemihepatic ischemia during
      hepatectomy.
AB  - Seventeen patients with chronic liver disease underwent prolonged warm ischemia
      of hemi-lobe during liver resection. Those included 15 cirrhotic patients and two
      with chronic hepatitis. The hemi-hepatic ischemia was carried out with a liver
      clamp. The normothermic liver ischemia time of 40 to 70 minutes (53.8 +/- 10.4
      minutes, mean +/- SD) were tolerated well with an acceptable postoperative course
      and no mortality. The liver with cirrhosis or chronic hepatitis can tolerate a
      hemi-hepatic ischemia of up to 70 minutes for patients with no high-risk factors.

PMID- 8530223
TI  - The role of percutaneous transhepatic cholecystostomy in the management of acute
      cholecystitis in high-risk patients.
AB  - A method recently developed that may be an appropriate solution for high-risk
      patients with acute cholecystitis is percutaneous sonography-guided
      cholecystostomy. We report our experience in 10 high-risk elderly patients with
      clinical and sonographic diagnosis of acute cholecystitis. Immediate regression
      and resolution of septic symptoms was achieved in all cases. One patient was
      operated on as soon as his clinical condition stabilized, with uneventful
      postoperative recovery. The other nine were considered inoperable; of these, two
      were readmitted within a few months with recurrence of symptoms who underwent
      surgery, with a long and complicated postoperative course. The only complication
      we observed was temporary septicemia in one patient immediately after completion
      of the procedure. In view of these findings, we consider percutaneous
      transhepatic cholecystostomy an effective and safe method of treatment for acute
      cholecystitis in critically ill patients. However, this procedure should be
      regarded as a preliminary measure only, to render the patient more suitable for a
      formal cholecystectomy. We report our results and discuss technical and principal
      matters concerning percutaneous transhepatic cholecystostomy in the light of the
      current literature.

PMID- 8530224
TI  - Expression of laminin in HCC treated with transcatheter arterial embolization.
      Usefulness of laminin staining as a post-surgical detection procedure at the
      tumor invasion boundary.
AB  - The distribution of laminin was studied in sixty surgically resected
      hepatocellular carcinomas (HCC) treated with transcatheter arterial embolization
      (TAE) using immunoperoxidase procedure. When increased, laminin patterns
      consisted of thick basement membranes, organized in a trabecular pattern, and
      were lined by sinusoid structures. A marked increase of laminin was seen in 63.4%
      of well differentiated HCC, and in only 9.1% of poorly differentiated HCC. No
      laminin positive cases were found among 8 cases of adenomatous hyperplasia (AH)
      containing HCC foci. Thus, laminin patterns in HCC may be related to the degree
      of tumor differentiation. At the tumor-non tumor boundary, differential
      expression of laminin has made it possible to discriminate overt cancerous
      regions from normal tissues. Thus, laminin status proved to be an effective
      marker for tumor invasion in well-differentiated, laminin positive tumors.
      Assessment of HCC by laminin staining, together with a thorough and precise
      pathological examination of viable tumor cells after TAE treatment, may be
      recommended as a detection procedure for tumor invasion and for the transition
      from AH to the premalignant condition which culminates in HCC.

PMID- 8530225
TI  - Recurrent common bile duct stones associated with periampullary duodenal
      diverticula and calcium bilirubinate stones.
AB  - We reviewed operative procedures, type of stones, and coexistence of
      periampullary duodenal diverticula in 115 patients with common bile duct stones
      who underwent first surgery at our department between 1982 and 1991. Among these
      patients, 109 underwent choledochotomy with T-tube drainage, 4 underwent side-to
      side choledocho-jejunostomy, and 2 had end-to-side choledochojejunostomy. Five
      patients developed recurrent common bile duct stones (RCS) after surgery. All
      these patients were older women who had calcium bilirubinate stones in the common
      duct and coexisting periampullary duodenal diverticula. No patients who underwent
      end-to-side choledochojejunostomy developed RCS after the initial surgery or
      reoperation. The results of the present study suggest that both calcium
      bilirubinate stones and periampullary duodenal diverticula are contributing
      factors in the development of RCS in patients with common bile duct stones, and
      that end-to-side choledocho-jejunostomy should be considered for patients with
      these two factors after the initial common duct exploration.

PMID- 8530226
TI  - Pancreaticoduodenectomy under epidural anesthesia without endotracheal intubation
      for the elderly.
AB  - To evaluate the efficacy of a single application of epidural anesthesia without
      endotracheal intubation for pancreaticoduodenectomy (PD), the data on 30 patients
      who underwent PD were analyzed for their operative morbidity and mortality. These
      patients were classified into two groups according to the type of anesthesia
      performed: 15 received epidural anesthesia alone (Group I) and 15, general
      anesthesia under endotracheal intubation (Group II). The clinical characteristics
      of the patients in both groups were comparable at the time of operation, except
      that Group I included a significantly larger proportion of elderly patients than
      Group II (p < 0.05). Postoperative pulmonary complications (PPCs) occurred in 5
      (33.3%) of the Group II patients, especially in elderly patients who underwent
      lengthy operations, whereas no such complications occurred in the Group I
      patients (p < 0.05), even in elderly patients with a long operating time. The
      curability of the malignant tumors and the incidences of other complications were
      not significantly different between the two groups. These findings suggest that a
      single application of epidural anesthesia is effective in preventing PPCs when
      performing a time-consuming PD, especially in elderly patients.

PMID- 8530227
TI  - Clinical study on hepatocellular carcinoma with extrahepatic malignancies.
AB  - In a consecutive series of 146 patients with hepatocellular carcinoma (HCC), 10
      patients (6.8%) were found to have one or two extrahepatic malignancies (EHM). Of
      these, eight had double cancers and two, triple cancers. The associated
      malignancies included eight cases of gastric cancer and four cases of colon
      cancer. Among the 12 lesions, eight were in the early stage. All the 10 patients
      were hepatitis B surface antigen negative. The incidence of coexisting liver
      cirrhosis and the retention rate of indocyanin green in 15 minutes among HCCs
      with EHM were significantly lower than those among HCC alone. These results
      suggest that the etiology of HCC with EHM is different from the etiology of HCC
      alone in Japan.

PMID- 8530228
TI  - Perioperative benzimidazole therapy in human hydatid liver disease.
AB  - Primary treatment of liver hydatidosis is surgical, but the recurrence rate is
      about 10%. To minimize the risk of recurrence, 67 consecutive patients with liver
      hydatidosis were prospectively treated by mebendazole or albendazole for 5 days
      before surgery. During the operation the viability of the protoscoleces was
      assessed. Seventeen patients who had viable protoscoleces at the time of the
      operation received the same benzimidazole one extra month postoperatively, while
      the remaining 50 patients who had dead protoscoleces didn't receive postoperative
      therapy. None of the patients developed recurrence of the disease after a follow
      up period of 15-67 months (average 41 months). These results suggest that a 5-day
      preoperative benzimidazole therapy either combined or not with a monthly
      postoperative course according to the viability of the protoscoleces at the time
      of operation, may erase the risk of recurrence after surgical treatment of the
      liver hydatidosis.

PMID- 8530229
TI  - Endoscopic adrenaline injection in treatment of bleeding peptic ulcers.
AB  - This study aimed to compare the results of bleeding peptic ulcer treated by
      endoscopic adrenaline injection with controls treated conventionally. Between
      January 1991 and December 1993, 69 patients with actively bleeding peptic ulcers
      with visible vessel received endoscopic adrenaline injection. This group of
      patients was compared with 31 endoscopically similar patients treated
      conventionally, using H2 blockers with or without surgery, from October 1987 to
      December 1990 prior to the introduction of endoscopic injection therapy in this
      hospital. Both groups of patients were comparable in terms of age, haemoglobin
      level on admission and site of ulcer (gastric or duodenal). Permanent haemostasis
      was attained with endoscopic adrenaline injection in 97% of our patients.
      Rebleeding occurred in 9% in the injected group vs 39% in the historical control
      group (p < 0.005). Three percent of patients in the injected group had emergency
      surgery compared with 48% in the control group (p < 0.005). The median hospital
      stay and transfusion requirements in the injected group were 6 days and 2 units
      respectively vs 8 days and 3 units in the control group but the difference was
      not statistically significant. We conclude that endoscopic adrenaline injection
      is effective in the treatment of bleeding peptic ulcer leading to a reduction in
      rebleeding rate and emergency surgery.

PMID- 8530230
TI  - Diagnostic approach and management of active lower gastrointestinal hemorrhage.
AB  - We evaluated 67 patients with acute bleeding of the lower gastrointestinal tract,
      for diagnostic accuracy of colonoscopy, and scintigraphy. Fifty-nine patients
      were stable after initial resuscitation and underwent colonoscopy. The source of
      hemorrhage was identified in 30 patients (50.8%). Tc-labeled red blood cells
      scintigram was undergone in 23 patients with a sensitivity of 43.4%. The
      identification of the bleeding source reached 75.4% when colonoscopy was used in
      combination with scintigraphy. Eleven patients with lower gastrointestinal
      bleeding requiring transfusion of 5 units of red blood cells or more had a
      diagnostic exploratory laparotomy, and the diagnosis was ascertained during
      operation in nine. The postoperative mortality rate was 18.1%. We conclude that
      in patients with active gastrointestinal bleeding, colonoscopy in combination
      with scintigraphy detect at a higher rate the cause and the site of bleeding and
      possibly improve the prognosis.

PMID- 8530231
TI  - Recurrent intraabdominal cancer with intestinal obstruction.
AB  - The objective of this study was to evaluate short and long term results of
      management of recurrent intraabdominal malignancy causing intestinal obstruction
      using surgery and intraperitoneal chemotherapy and determine the clinical
      features that suggest favorable outcome. Forty two consecutive patients who were
      treated by cytoreductive surgery with or without intraperitoneal chemotherapy
      were retrospectively analyzed. There were 20 patients with primary tumors of
      appendix, 13 with cancer of colon or rectum, and 9 patients with cancer of other
      origins. All 42 patients were explored and extensively evaluated
      intraoperatively. Surgery included bowel resections and peritonectomy procedures.
      In 30 patients early postoperative intraperitoneal chemotherapy was administered.
      The overall morbidity was 55% while mortality was 7.14%. The projected three year
      survival for this group of patients was 32.7%. Among the most significant
      clinical features that reflect favorable prognosis were low histologic grade of
      malignancy, recurrence 2 and more years after primary surgery, and cancer that
      could be completely surgically excised. As a result of treatment patients'
      performance status improved in 47.6% of cases. An aggressive reoperative approach
      may be considered for palliation of selected patients with recurrent cancer
      causing intestinal obstruction.

PMID- 8530232
TI  - Intra-abdominal tuberculosis in acquired immunodeficiency syndrome. Diagnosis and
      management.
AB  - Tuberculosis (TB) in human immunodeficiency virus (HIV) immunosuppressed patients
      is characterized by extra-pulmonary disease in as many of 70% of them. If
      intestinal or lymph node involvement occurs, the differential diagnosis between
      an acute abdomen and other non surgical conditions may be a challenging problem.
      The authors analyzed eight double infected patients (TB and acquired
      immunodeficiency syndrome AIDS), who were admitted to the University Hospital
      (HUCFF) of the Federal University of Rio de Janeiro. This association should be
      considered when abdominal pain, anemia, fever, weight loss and abdominal lymph
      node enlargement are present. Bacteriology of body fluids, abdominal ultrasound
      (US) and computed tomography scans (CT) combined with guided needle aspiration
      biopsies, barium examination, colonoscopy and laparoscopy, can not only elucidate
      the diagnosis but also be helpful in assessing an appropriate management. Thus a
      systematic evaluation often yields an etiology and a correct therapeutic
      indication reducing the high mortality rate.

PMID- 8530233
TI  - Effect of pentoxifylline on the ischemia-reperfusion injury of the intestine.
AB  - Intestinal ischemia is a common clinical event and reperfusion results in further
      tissue damage exceeding that of ischemia alone. The present study was designed to
      test this and to assess the role of pentoxifylline, (administered intravenously
      as a bolus dose of 25 mg/kg in 1 ml normal saline, followed by continuous
      infusion of 0.2 mg/kg/minute for 95 minutes), in ischemia-reperfusion injury of
      the rat intestine. Intestinal ischemia was produced by occlusion of the superior
      mesenteric artery (SMA) with interruption of the collateral flow for 30 minutes.
      Reperfusion was established by declamping the (SMA) for 1 hour and evaluation of
      the mucosal damage was determined using a grading scale from 0 to 5, with
      estimation of mean mucosal thickness, villous height and crypt depth. The grade
      of mucosal damage, mucosal thickness, villous height and crypt depth were 2.2,
      407 microns, 210 microns, and 196 microns respectively in the ischemia group, and
      3.6, 327 microns, 156 microns, and 171 microns respectively in the ischemia
      reperfusion group, while these values in ischemia reperfusion with administration
      of pentoxifylline group were 2.5, 505 microns, 294 microns, and 200 microns
      respectively. The severity of the tissue injury increased considerably after
      reperfusion of the ischemic intestine and pentoxifylline was effective in
      attenuating the reperfusion injury significantly.

PMID- 8530234
TI  - Modality of failure following resection of stage I and stage II non-small cell
      lung cancer.
AB  - The pattern and sites of recurrence were studied in 270 patients with resected
      Stage I (NO) or Stage II (Nl) non-small cell lung cancer (NSCLC). Survival,
      incidence, and type of intrathoracic locoregional recurrence versus distant extra
      thoracic recurrence after surgical excision were analyzed. Prognostic parameters,
      such as postsurgical stage, histologic type, degree of cellular differentiation,
      and surgical approach, were examined to discern their influence on tumor
      recurrence. The total incidence of recurrence in patients with stage I and II
      tumors was high, with a radical surgical approach often resulting ineffective,
      because of incomplete locoregional neoplastic extirpation due to micrometastases.
      Lymph node metastases worsened prognosis, with Nl tumors demonstrating a
      significantly higher recurrence rate at 5 years (63%) than NO neoplasms (48%) (p
      < 0.01). Stage I tumors showed an elevated incidence of local recurrence (45%),
      with tumor T-factor making a significant contribution in such cases. N1-factor
      combined with an elevated T-factor (Stage II Subclass pT2Nl neoplasms) promoted a
      higher incidence of distant rather than local recurrence. A shorter disease-free
      interval was observed in patients with N tumors as opposed to NO neoplasms.
      Histologic type did not play a statistically significant role (p = ns) in the
      total incidence of recurrence. A similar total incidence of recurrence was
      observed in Stage I and II tumors treated by lobectomy (51%) or pneumonectomy
      (56%), with locoregional recurrence appearing more frequently after lobectomy.

PMID- 8530235
TI  - Recurrence and mortality in patients with differentiated thyroid carcinoma.
AB  - We examined the factors associated with increased recurrence and/or mortality of
      195 patients with primary differentiated thyroid carcinoma. Of 171 patients who
      underwent at least, resection of the primary macroscopic tumor (curable), 26
      patients (15%) developed recurrence and 6 of these patients died from the
      disease. Sixteen (67%) of 24 patients with initial distant metastasis or grossly
      malignant tumor residua in the neck after the operation (non-curable patients)
      died from the disease. In the curable patients, age, sex and tumor size
      correlated significantly with recurrence and/or mortality. When the
      characteristics of patients who died after recurrence were compared to those who
      survived after recurrence, however, only the patient's age correlated
      significantly with mortality. In the non-curable patients, the histologic subtype
      correlated significantly with mortality. It may be concluded, therefore, that the
      risk factors which affect mortality in differentiated thyroid cancer differ
      between curable and non-curable patients.

PMID- 8530236
TI  - Laparoscopic hysterectomy: is dissecting the ureter necessary?
AB  - Laparoscopic hysterectomy has been first reported by Reich et al. in 1989, which
      confirmed the possibility of laparoscopic hysterectomy being employed as a
      replacement of the vast majority of traditional abdominal hysterectomies. There
      are three critical points in laparoscopic hysterectomy. The most important
      critical point is to identify uterine arteries from the ureter in the
      paracervical area. Several ureteral injuries at operative laparoscopy have been
      reported. We performed two hundred and thirty laparoscopic hysterectomies during
      the period from March 1991 to October 1993. Sixty patients were later included in
      this study. Thirty of these applied the technique of dissecting the ureter at the
      initiation of laparoscopic hysterectomy. Most of the patients were discharged on
      the second postoperative day. Although dissecting the ureter at the beginning of
      the operation did not produce a significant discrepancy in operation time, blood
      loss, hospitalization day and ureter injury when compared with the control group,
      the uterine arteries, however, may be confidently desiccated once the path of the
      ureter near the uterosacral ligament is identified.

PMID- 8530237
TI  - Emergency cerclage compared with bed rest for advanced cervical dilatation in
      pregnancy.
AB  - In a cohort of 43 women with viable, singleton pregnancies, cervical dilatation
      greater than 4 cm, and absent labor between 20 and 27 weeks gestation, 22 women
      who underwent emergency cerclage within six hours of admission, were compared
      prospectively with 15 women who elected conservative bed rest treatment. The two
      groups were demographically similar. Emergency cervical cerclage resulted in a
      longer mean gestational age at delivery compared to bed rest (p = 0.001). Women
      treated with cerclage required a significantly shorter period of antepartum
      hospitalization (p = 0.001), required less tocolysis (p = 0.005), and experienced
      fewer preterm membrane ruptures compared to women in the bed rest group (p =
      0.01), although the latency period, following preterm rupture of membranes was
      shorter in the cerclage group (p = 0.005). There was no statistical difference in
      the frequencies of chorioamnionitis, maternal morbidity and cesarean section
      between the two groups. Although the perinatal mortality in the two groups was
      not significantly different (p = 0.3), emergency cerclage resulted in a
      significantly higher mean birth weight compared to conservative bed rest
      treatment (p = 0.02). This study demonstrates the superiority of emergency
      cerclage to bed rest in women with advanced cervical dilatation and absent labor
      in late second-trimester of pregnancy.

PMID- 8530238
TI  - Primary hyperaldosteronism. Analysis of risk factors associated with persistent
      postoperative hypertension.
AB  - Between 1983 and 1992, 24 patients with primary hyperaldosteronism were operated
      at our division. Among these, 21 had adrenal adenoma and constituted the subjects
      of our study. The aim of this retrospective study was to determine risk factors
      that could potentially lead to persistent arterial hypertension (5 cases or
      23.9%). The variables of the univariate and the multivariate analyses were: sex,
      age, diameter of the neoplasm, preoperative duration of the hypertension, and
      familial hypertension. The analysis demonstrated no statistically significant
      difference between the resolution of hypertension and the variables. Though not
      statistically significant, the only variable that approached statistical
      significance (p < 0.11) was familial hypertension.

PMID- 8530239
TI  - Early results of operative closure of pressure sores in traumatic paraplegics.
AB  - The development of pressure sores in the course of management of a paraplegic
      represents a major setback which will not only delay rehabilitation but prolong
      hospital stay. Pressure sores may heal under conservative management provided the
      site is relieved of pressure. This mode of treatment is associated with prolonged
      immobilisation and is accompanied by a higher incidence of recurrence. Since in
      our unit pressure sores are mostly closed with flaps, we decided to review our
      early results. Between 1981 and 1986, 28 patients with 61 pressure sores were
      surgically closed at the National Orthopaedic Hospital, Enugu, Nigeria. The 29
      trochanteric sores were closed with tensor fascia lata (TFL) myocutaneous flap.
      Sacral sores were closed with bilateral gluteal flaps or a rhomboid flap. Most
      ischial sores were closed with gracilis myocutaneous flap. Overall 72.1% of our
      cases healed primarily with no complications. There were 3 major complications
      requiring reoperation and 14 minor complications which healed on conservative
      management with daily dressing. We conclude that operative closure of pressure
      sores in traumatic paraplegics is advocated as this affords the greatest benefit
      to the patients.

PMID- 8530240
TI  - The integration of diagnostic tests and the role of outpatient surgery in the
      management of breast disease.
AB  - The aim of the earliest possible diagnosis of breast carcinoma achieved through
      the integration of clinical, mammographic, sonographic and cytologic data has
      determined an increased detection of breast lesions and a greater accuracy in
      their description. Nevertheless, the nature of some of these lesions cannot be
      well-defined because of their biological characteristics and their physical,
      radiological or cytological aspects. The need to obtain a definitive diagnosis in
      any case has given rise to a paradoxical increase in histologic examinations: in
      specific conditions and for certain kinds of lesions, outpatient surgery under
      local anesthesia could very well represent a supplementary tool in the diagnostic
      and therapeutic strategy for the management of breast lesions. The data here
      reported concern 397 breast lesions for which it was thought appropriate to
      complete the diagnostic procedure with the surgical excision on an outpatient
      basis under local anesthesia. Excluding the 3 breast lymphomas and the 19 loco
      regional recurrences, for which the purpose of outpatient surgery was
      therapeutic, at the histologic examination 35% benign lesions, of which 91
      associated with an increased risk of breast cancer, were found, as well as 11 in
      situ and 10 invasive carcinomas (false negatives), with a therapeutic option
      error of 2.5%. Now that one of the principal aims of public management is to put
      a check on health expenditures, outpatient surgery would contribute to obtaining
      the correct balance between proper management of breast lesions and low
      cost/effective ratio.

PMID- 8530241
TI  - Thrombolysis of peripheral graft occlusion in patients with hypertension.
AB  - The objective of this study was to evaluate the effect of hypertension on the use
      of thrombolytic therapy in patients with occluded synthetic peripheral bypass
      grafts. Thrombolysis with urokinase was performed in 44 cases of occluded lower
      extremity bypass grafts. The cases were divided into two groups: Group I
      consisted of patients currently being treated for hypertension. Group II
      consisted of patients without a history of hypertension. A comparison of pre- or
      intra-lytic data revealed that there was no significant difference in each group.
      Complications occurred in 15 (32.6%) out of 46 cases. There was no significant
      increase in complication when the risk factors were compared. In Group I, the
      one, two, and three year patency rates were 42.7%, 23.0%, and 7.7% and the limb
      salvage rates were 93.3%, 73.9%, and 73.9% for one, two, and three years
      respectively. The Group II patency rates were 70.6%, 41.6%, and 41.6% and the
      limb salvage rates were 94.1%, 86.9%, and 86.9%. The patency rate was
      significantly reduced when Group I was compared to Group II (p < 0.05). There was
      no statistically significant difference in limb salvage rates between Groups I
      and II. In conclusion, hypertension is one of the important risk factors that
      reduce the patency rate after thrombolytic therapy in patients with peripheral
      arterial bypass graft.

PMID- 8530242
TI  - Splenic arteriovenous fistula.
AB  - Splenic arteriovenous fistulas are uncommonly encountered, yet they can invoke
      serious pathophysiological consequences. Four patients treated for splenic
      fistulas at our institution over the last decade were combined with all previous
      case reports to produce the most extensive review yet reported, totalling 91
      patients. Common etiologies included atherosclerotic aneurysm rupture (44%),
      congenital malformation (20%), and prior splenectomy (13%). The most frequent
      manifestation was gastrointestinal hemorrhage (48%), which was most prevalent
      with congenital fistulas (61% p < 0.05) or fistulas located proximally (54%, p <
      0.005). Chronic portal hypertension that was usually characterized by
      preservation of hepatic function developed in 65%. Management included
      splenectomy (70%), fistula excision (59%), and occasionally required distal
      pancreatectomy (10%). Persistent portal hypertension necessitated operative
      portosystemic shunting in select cases (9%), with an overall 30 day operative
      mortality of 9%. While percutaneous embolization provided an additional
      therapeutic option in 4%, optimal management continues to include operative
      intervention.

PMID- 8530243
TI  - Surgical treatment of adrenal metastasis following pulmonary resection for lung
      cancer: comparison of adrenalectomy with palliative therapy.

PMID- 8530244
TI  - Cholecystectomy: comparison of minilaparotomy and laparoscopy.
AB  - Laparoscopic cholecystectomy (LC) has become the most popular method of removing
      the gallbladder. Because it is an expensive operation requiring special training
      for the team, LC has been challenged by other methods of minimal-access surgery,
      e.g. by minilaparotomy (MC). This study was planned to be a single-surgeon
      prospective random study to compare minilaparotomy cholecystectomy (MC) and
      laparoscopic cholecystectomy (LC), but was never done over the pilot phase.
      Twenty-four cholecystectomies were included, eight MC and 16 LC, the patients
      being comparable between the groups. In the MC group three patients (37%) had
      complications versus no complications in the LC group (p = 0.028). Postoperative
      hospital stay was longer in the MC group (median three days) than in the LC group
      (median one day), even when the patients with complications were excluded. Due to
      these discouraging experiences the extended random study was never done, and MC
      was abandoned.

PMID- 8530245
TI  - PACs are a reality.

PMID- 8530246
TI  - The right to privacy vs the public's right to know.

PMID- 8530247
TI  - Another physician on the front line in WWII.

PMID- 8530248
TI  - Is Iowa complying with HCFA guidelines?

PMID- 8530249
TI  - Greg Ganske on Medicare reform.

PMID- 8530250
TI  - Apnea and vomiting in an infant due to cocaine exposure.

PMID- 8530251
TI  - Have I been a good parent?

PMID- 8530252
TI  - Complement system in coronary heart disease: a review.

PMID- 8530253
TI  - Reversal of multiple-site tumor cell-induced immunosuppression by specific
      cytokines and pharmacological agents.
AB  - The present study explores a model for tumor cell-induced immunosuppression and
      reversal of suppression by cytokines and other pharmacological agents. To
      simulate tumor-cell-induced suppression, a panel of suppressor agents which
      included CsA (cyclosporin A), SSP (staurosporine), BSO (L-buthionine-[S,R]
      sulfoximine) and PMA, and a panel of anti-suppressor agents which included IL-2,
      IL-4, GSH (glutathione) and amiloride, were tested. These suppressor/anti
      suppressor agents acted differently on four specific sites of the immune arm that
      affected the alpha CD3-induced T cell proliferative and cytotoxic responses. They
      included (1) IL-2 production, (2) PKC-regulated cytolytic granule production, (3)
      GSH-regulated maturation of functional granules, and (4) granule exocytosis. When
      a single suppressor agent was used, all the suppressor agents tested in this
      study inhibited the generation of alpha CD3-induced activated killer cells (CD3
      AK), whereas alpha CD3-induced proliferation was inhibited by CsA, BSO, and EL-4
      tumor cells. Except for EL-4, suppression induced by a single suppressor agent
      could be corrected by an appropriate single anti-suppressor agent. Multiple
      suppressor agents induced profound suppression of CD3-AK response. In most cases,
      multiple anti-suppressor agents were required to correct the immune defects
      induced by multiple suppressor agents. Finally, EL-4 tumor-cell-induced
      immunosuppression could not be corrected by any single anti-suppressor agent
      tested, but a combination of IL-4, GSH and amiloride fully restored the CD3-AK
      response. These results suggest that tumor cells may induce multiple immune
      defects that require multiple anti-suppressor agents for correcting the defects
      to restore the host immunocompetence.

PMID- 8530254
TI  - Established murine lupus nephritis does not respond to exogenous interleukin-1
      receptor antagonist; a role for the endogenous molecule?
AB  - Interleukin 1 beta (IL-1 beta) is a potent inflammatory cytokine and IL-1 beta
      gene expression is elevated in the kidneys of mice with lupus nephritis. This
      study was designed to examine whether pharmacological administration of the IL-1
      receptor antagonist (IL-1ra) would reduce the inflammation in MRL lpr/lpr mice
      with lupus nephritis. Human recombinant IL-1ra (RA) or saline (SA) was infused by
      intraperitoneal osmotic minipumps in 16 week old mice (n = 9, group RA or n = 12,
      group SA, respectively). Age matched MRL +/+ mice served as normal controls. At
      the end of 4 weeks of treatment glomerular filtration rates (5.4 +/- 0.4 vs 5.6
      +/- 0.4 ml/min/kg BW), proteinuria (6.0 +/- 1.0 vs 5.5 +/- 1.2 micrograms
      IgG/day) glomerular volumes (571 +/- 30 vs 509 +/- 25 microns3 x 10(3)),
      mesangial volumes (172 +/- 23 vs 158 +/- 17 microns3 x 10(3)), and
      cells/glomerulus (519 +/- 51 vs 506 +/- 47) were not significantly different
      between RA and SA groups respectively. There was also no significant differences
      in spleen sizes, plasma IgG and anti-dsDNA antibody levels despite achieving
      levels of IL-1ra of over 0.8 microgram/ml in RA mice. Circulating IL-1 was not
      detected by bioassay in the plasma of diseased or normal mice. In fact, diseased,
      saline treated mouse plasma inhibited the cell proliferation assay in the
      presence of IL-1, and dilution studies showed that the endogenous inhibitors were
      of high titre. Although IL-1 may play a role in the renal injury of lupus
      nephritis, pharmacological inhibition with IL-1ra in animals with established
      injury is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8530255
TI  - The inhibitory effect of preoperative immunochemotherapy on the lymph node
      metastasis of murine MM48 tumor.
AB  - A murine tumor model showing metastases to lymph nodes (LN) was established by
      intradermally implanting highly metastatic MM48 tumor cells (2 x 10(6)) in
      C3H/HeN mice. We were searching for the most effective immunochemotherapeutic
      modality to treat this metastatic tumor. The combination therapy with
      chemotherapeutics, granulocyte colony-stimulating factor (G-CSF) and OK-432 on
      Days 8-11 was found to be remarkably effective, making the solid tumor disappear
      in more than half of the treated mice, though all of them eventually died of LN
      metastasis, as all the control mice did. Then an attempt was made to cure the
      mice from such fatal metastatic tumors with combined immunochemotherapy prior to
      surgical resection on Day 14. The combination therapy with chemotherapeutics, G
      CSF and OK-432 more strongly inhibited the metastases then, and more than 85% of
      the mice survived. When the survivors were rechallenged with MM48 tumor cells,
      all of them rejected and survived without recurrences and metastases, indicating
      the acquirement of specific immunity. It is expected that this preoperative
      immunochemotherapy may be clinically useful for the treatment of malignant
      neoplasms.

PMID- 8530256
TI  - Nigella sativa: effect on human lymphocytes and polymorphonuclear leukocyte
      phagocytic activity.
AB  - The effects of Nigella sativa (N. sativa) seeds and their soluble fractions were
      studied in vitro on lymphocyte response to different mitogens and on
      polymorphonuclear leukocyte phagocytic activity. No stimulatory effect of N.
      sativa was detected on lymphocyte response to phytohemagglutinin, concanavalin-A
      or pokeweed mitogen. A stimulatory effect of N. sativa was noticed on the
      lymphocyte response to pooled allogeneic cells. This effect was more pronounced
      when the low molecular weight (< 10 kDa) fraction was used and varied from one
      normal individual to another (25% to 825%). N. sativa enhanced the production of
      interleukin-3 by human lymphocytes when cultured with pooled allogeneic cells or
      without any added stimulator. N. sativa did not, however, enhance or suppress
      interleukin-2 secretion by mitogen activated peripheral blood mononuclear cells.
      Interestingly, N. sativa increased interleukin-1 beta, suggesting therefore, that
      it has an effect on macrophages. It also suppressed the leukocyte
      chemiluminescence activity using phorbol myristate acetate and Zymosan as
      stimulants. No effect of N. sativa or its fractions was, however, noticed on
      bacterial phagocytosis or killing when Staphylococcus aureus was used, indicating
      that the decrease in chemiluminescence activity in the presence of N. sativa is
      not relevant to the bactericidal activity.

PMID- 8530257
TI  - Effect of soluble fungal (1-->3)-beta-D-glucan obtained from Sclerotinia
      sclerotiorum on alveolar macrophage activation.
AB  - In this study, we examined the effect of systemic administration of SSG, a
      soluble highly branched (1-->3)-beta-D-glucan obtained from a fungus Sclerotinia
      sclerotiorum IFO 9395, on pulmonary immune responses in mice. SSG (10 mg/kg)
      administered intravenously (i.v.) rapidly leaked into the alveolar space and
      enhanced several functions of alveolar macrophages (AMs), such as phagocytic
      activity, lysosomal enzyme activity, active oxygen secretion and cytokine
      production, on day 1 post-administration. However, kinetic changes of influx of
      SSG into alveoli and AM activation after SSG treatment were different. The
      enhanced AM functions decreased to control value on day 2 when SSG still existed
      at the alveolar space. Additionally, a high dose (500 micrograms/ml) of SSG was
      needed to activate AMs in vitro. These data imply that the stimulation by SSG
      alone is not effective on AM activation. SSG administered i.v. also augmented
      interferon gamma (IFN gamma) mRNA expression in the lung tissue, and the kinetic
      change of the expression was similar to that of AM activation. Additionally, a
      synergistic effect of SSG and IFN gamma was observed on AM activation in vitro.
      It may be possible that IFN gamma produced by pulmonary T cells is one of the
      important factors for AM activation in vivo by SSG injection. Furthermore, SSG
      administered i.v. enhanced candidacidal activity and cytolytic activity against
      pulmonary metastatic Lewis lung carcinoma (3LL) cells of AMs, and inhibited
      significantly the experimental pulmonary metastasis of 3LL cells. These
      observations are very useful for the clinical application of SSG as a biological
      response modifier (BRM).

PMID- 8530258
TI  - Suppression of human immunoglobulin E antibody production by a new naphthalene
      derivative.
AB  - A new naphthalene derivative, (E)-2-(7-(2-naphthyl)-6-heptenamide)benzoic acid
      (TEI-8364) was assessed for its effect on interleukin (IL)-4- and anti-CD40
      monoclonal antibody-induced immunoglobulin E (IgE) production by cultured human
      lymphocytes. TEI-8364 preferentially suppressed the production of IgE by
      peripheral blood mononuclear cells (PBMC) in a dose-dependent manner, without
      inhibiting PBMC proliferation. In addition, TEI-8364, at a concentration of 10
      microM, completely inhibited IL-4- and anti-CD40-induced IgE production by
      purified tonsillar B lymphocytes, suggesting that TEI-8364 affects B cells by
      interfering with signals provided by IL-4 or through CD40 and IL-4. TEI-8364 also
      had a profound inhibiting effect on the in vitro production of specific antibody
      to a T cell-dependent antigen by PBMC from an immunized volunteer, cultured in
      the presence of antigen. Furthermore, TEI-8364 at a dose of 1 mg/mouse/day
      selectively inhibited IgE production by severe combined immunodeficiency mice
      engrafted with human PBMC, if the drug was administered subcutaneously for five
      consecutive days. These findings suggest that TEI-8364 is a potent therapeutic
      agent that may be useful in the treatment of IgE-mediated allergic disorders.

PMID- 8530260
TI  - Medical technology assessment and ethics. Ambivalent relations.

PMID- 8530259
TI  - Dexamethasone inhibits nitric oxide-mediated cytotoxicity via effects on both
      macrophages and target cells.
AB  - In order to evaluate the mode of action of dexamethasone (DEX) on macrophage
      mediated cytotoxicity and to understand its association with nitric oxide (NO)
      production, the effect of DEX on macrophage- and spermine NONOate-mediated
      cytotoxicity was studied. DEX caused 100% inhibition of cytotoxicity by LPS- and
      IFN gamma-activated macrophages whereas it caused only partial inhibition of NO
      production. Inhibition of macrophage-mediated cytotoxicity by DEX was not
      reversed by supplementation of rTNF alpha. The partial inhibition of NO
      production by DEX was due to partial inhibition of iNOS mRNA expression.
      Incubation of macrophages with DEX for up to 24 h prior to activation did not
      cause further inhibition of NO production. DEX failed to inhibit NO production if
      added 6 h after addition of LPS and IFN gamma. Addition of P815 cells after the
      onset of NO production resulted in partial restoration of cytotoxicity in DEX
      treated macrophages. Incubation of P815 cells with spermine NONOate, a synthetic
      NO donor, resulted in P815 cell lysis, which was dose-dependent, had a lag phase
      of 3 h and was blocked by hemoglobin. DEX also inhibited spermine NONOate
      mediated tumor cell lysis, indicating that DEX may have a protective effect on
      tumor targets. These results indicate that DEX inhibits macrophage-mediated
      cytotoxicity by decreasing NO production and by inhibiting the cytotoxic effects
      of NO on the target cells.

PMID- 8530261
TI  - Abortion and the maternal-fetal medicine physician.

PMID- 8530262
TI  - Abortion and the maternal-fetal medicine physician.

PMID- 8530263
TI  - Abortion and the maternal-fetal medicine physician.

PMID- 8530264
TI  - Abortion and the maternal-fetal medicine physician.

PMID- 8530265
TI  - Visions, secular and sacred.

PMID- 8530266
TI  - My conscience, your money.

PMID- 8530267
TI  - Horton hatches the egg.

PMID- 8530268
TI  - Fetal privacy and confidentiality.

PMID- 8530269
TI  - Animal organs for human patients?

PMID- 8530270
TI  - Sex, money, and bioethics. Watching ER and Chicago Hope.

PMID- 8530271
TI  - Baboon marrow transplant given OK.

PMID- 8530272
TI  - The seductive sirens of medical progress. The case of xenotransplantation.

PMID- 8530273
TI  - Rethinking transplantation between siblings.

PMID- 8530274
TI  - Genetic influence in headaches: a Swedish twin study.
AB  - The heritability of liability to self-reported migraine and nonmigrainous
      headaches was examined in two large cohorts from the Swedish Twin Registry
      consisting of 6448 (the older cohort) and 12,884 (the younger cohort) like-sexed
      twin pairs. Higher concordance rates were consistently found for lifetime
      migraine among the monozygotic twins than in the dizygotic twins, as well as for
      migraine headaches of the recurrent disabling type. In addition, a higher
      concordance rate was found among the monozygotic twins than in dizygotic twins in
      a "mixed" group of possible tension-type or mild migraine headaches (or both).
      The results of structural equation model-fitting analyses showed that genetic
      effects for migraine headaches were stronger for the females (estimates ranging
      from 49% to 58%) than for the males (39% to 44%) in the two cohorts. Unique
      nonshared environmental effects were greatest for the "mixed" group in both sexes
      (estimates ranging from 60% to 69%). The results are discussed in view of similar
      large-scale twin studies examining the heritability of liability to migraine.

PMID- 8530275
TI  - Headache associated with aseptic meningitis.
AB  - A retrospective analysis of all patients admitted with the diagnostic codes of
      aseptic or viral meningitis was performed at two institutions over 3 years. Forty
      one patients with cerebrospinal fluid confirmation of aseptic meningitis
      (increased protein; increased white count; negative gram stain; and negative
      fungal, tuberculosis, and bacterial cultures) were analyzed. All the patients had
      headache, which was typically severe and bilateral in 39 of the 41 patients. The
      headache was of abrupt onset or the worst of the patient's life in 24 of the
      patients. The quality of the headache, when described, was usually throbbing (11
      of 14). Nineteen patients had prodromal symptoms, including malaise, myalgia,
      gastrointestinal symptoms, and urinary tract infections. All had associated
      symptoms, including nausea (25), vomiting (23), photophobia (18), stiff neck
      (25), and back pain (11). Thirty patients were febrile. Lumbar puncture was
      performed for headache and fever unexplained by systemic illness in 30 patients,
      meningeal signs in 15, headache of abrupt onset or the worst headache ever in 24,
      neurologic signs or symptoms in 12, and for other reasons in 2. Computerized
      tomography, when performed, was negative in all cases. Focal neurologic findings
      were present in 5 patients, a decreased level of consciousness in 6, and
      papilledema in 1. A severe headache that worsens, is abrupt in onset, or is the
      worst of the patient's life could be due to aseptic meningitis, bacterial
      meningitis, or a subarachnoid hemorrhage. Although not universally present,
      meningeal signs, fever, and neurologic signs or symptoms should alert one to a
      possible central nervous system infection.

PMID- 8530276
TI  - The relationship of locus of control and psychosocial-behavioral response in
      chronic headache.
AB  - It has been suggested that patients' perceptions of the impact chronic headache
      has on their lives as well as perceived control of their headaches may be
      associated with the intensity, duration, and exacerbation of pain they
      experience. The present study examined associations among International Headache
      Society (IHS) diagnostic category, pain characteristics such as severity and
      duration, perceived impact and control of headaches, and adaptive response. Two
      hundred twenty-five patients with migraine, tension-type, or combined migraine
      and tension-type headache served as subjects. General activity level was related
      to IHS diagnosis, with migraine headache patients reporting that they are more
      active than tension-type headache patients (F(2, 196) = 5.69, P < .01). Headache
      locus of control was not significantly related to IHS diagnosis, however external
      headache locus of control was significantly related to headache intensity (r =
      .32, P < .001, r = .25, P < .001), as well as to patients' perceptions of the
      extent to which pain interfered with various domains of their lives (r = .33, P <
      .001, r = .28, P < .001), and adaptive response (F(6, 402) = 4.68, P < .001). It
      appeared that perceived control over headaches and perceived impact of headaches
      were not related to IHS diagnostic category and were not strongly related to each
      other, but were related to headache severity.

PMID- 8530277
TI  - Headache disability inventory (HDI): short-term test-retest reliability and
      spouse perceptions.
AB  - We have reported previously that the 25-item Headache Disability Inventory has
      good internal consistency reliability, robust long-term (2 month) test-retest
      stability, and good construct validity. We conducted further investigations to
      evaluate the short-term (1 week) test-retest reliability and spouse perceptions
      of patients' self-perceived headache disability. The short-term test-retest
      reliability of the Headache Disability Inventory was excellent. Additionally, the
      spouse and patients' perceptions of the patient's headache disability generally
      were congruent, although we observed instances where the differences were marked.

PMID- 8530278
TI  - Valproic acid treatment of chronic daily headache.
AB  - The efficacy of valproic acid in the treatment of intractable chronic daily
      headache, unresponsive to traditional prophylactic medications, was examined
      prospectively in 16 patients. Dosage of the medication was adjusted to maintain
      serum valproic acid levels between 50 and 100 micrograms/mL, provided there were
      no significant side effects at that level. Valproic acid prophylaxis was of some
      benefit in only 2 of 16 patients. One of these two patients discontinued therapy
      due to side effects. Eight of the 16 patients reported side effects which
      included nausea, diarrhea, anorexia, lethargy, sleepiness, confusion, blurred
      vision, and decreased libido. In conclusion, valproic acid was not effective in
      controlling chronic daily headache in the majority of patients in whom
      conventional therapy had failed, and 50% of patients reported side effects. There
      is a significant disparity in the reported efficacy of this drug in treating
      chronic daily headache. This disparity is most likely due to the poorly-defined
      nature of this variety of headache. It is, therefore, recommended that more
      stringent definition of this disorder be developed before therapeutic regimens
      are evaluated.

PMID- 8530279
TI  - Headache associated with transient ischemic attacks.
AB  - Sixty (29%) of 205 consecutive patients with transient ischemic attacks
      registered in a hospital stroke data base had headache within 72 hours of onset.
      Headache was significantly more common in nonsmokers (odds ratio = 2.8; 95%
      confidence interval = 6.7 to 1.2). Headache was infrequent in patients with
      amaurosis fugax, and was not significantly associated with any other particular
      clinical presentation of transient ischemic attack. Headache was more common in
      vertebrobasilar (33%) than in carotid distribution (24%) episodes, and was not
      rare in transient ischemic attacks presenting as lacunar syndromes (29%).
      Headache was less frequent in patients whose computerized tomograms showed an
      infarct appropriate to the symptoms (odds ratio = 0.2; 95% confidence interval =
      0.02 to 1.4). A diffuse headache was more common in patients with lacunar events
      than in patients with cortical attacks (odds ratio = 3.0; 95% confidence interval
      = 13 to 0.07). No other association was found between headache location and the
      presumed involved vascular territory. Headache in patients with transient
      ischemic attacks is poorly related/explained by the clinical characteristics of
      the ischemic event.

PMID- 8530280
TI  - A piroxicam derivative partly effective in chronic paroxysmal hemicrania and
      hemicrania continua.
AB  - Piroxicam beta-cyclodextrin has recently been observed to be equal to, or even
      possibly to be superior to, indomethacin (mainly with regard to side effects) in
      a single case of hemicrania continue. Piroxicam beta-cyclodextrin, 20 to 40 mg
      per day, was, accordingly, tried in six patients with chronic paroxysmal
      hemicrania and six patients with hemicrania continua with a previously proven
      response to indomethacin. The study was conducted over a period of 3 weeks and in
      an open fashion. A placebo effect is considered to be negligible in these
      disorders. In such a comparison, piroxicam beta-cyclodextrin seemed inferior to
      indomethacin, in particular in chronic paroxysmal hemicrania.

PMID- 8530281
TI  - Clinical experience with headaches in preadolescent children.
AB  - We have reviewed the diagnoses of 654 children aged from 7 to 14 years who
      attended a neurologist for headache evaluation. Headaches beginning between the
      age of 7 and 14 represented a higher percentage (18.3%) than the proportion of
      preadolescent children in our health area (12.9%). Headaches were more common in
      girls; although cluster, posttraumatic, benign exertional headaches, and the only
      case of brainstem glioma were restricted to boys. Despite the female
      predominance, the proportion of males with migraine was significantly higher in
      the preadolescents than in the over 15 age group. Migraine accounted for the
      majority of diagnoses (609-93% of the total series), while tension-type headache
      (27-4%), and headache associated with sinus infection (7-1%) were the diagnoses
      which followed in frequency. There were only two headaches (0.3%) associated with
      intracranial masses. Even though, in terms of frequency, headache is a very
      common reason for neurology consultation, the present results show that the
      majority of preadolescents consulting because of headache suffer from benign
      conditions.

PMID- 8530282
TI  - EMG levels in children who suffer from severe headache.
AB  - Very little information exists about the physiology of pediatric headache and in
      particular, the role that skeletal musculature plays in the genesis of head pain.
      This study explored EMG levels in the neck and forehead in a group of 12 children
      who complained of severe headache. Comparisons were made with a matched group of
      12 children who were headache-free. Results suggested that children with headache
      suffer from very tense neck muscles which may reflect high levels of anxiety.

PMID- 8530283
TI  - Spontaneous intracranial hypotension: headache with a reversible Arnold-Chiari
      malformation.
AB  - Spontaneous intracranial hypotension is characterized by severe postural headache
      in the setting of low CSF pressure, usually attributed to a cryptic CSF leak. We
      report a patient whose prolonged refractory headache was characterized by the
      clinical symptoms of occipital neuralgia, but was also associated with the
      radiographic appearance of an Arnold-Chiari malformation, type I and low CSF
      pressure. After extensive diagnostic evaluation, CT cisternomyelography
      ultimately demonstrated a CSF leak at the C2 vertebral level. Symptomatic relief
      was sustained only with long-term theophylline administration. The apparent
      Arnold-Chiari malformation resolved with treatment of the low CSF pressure.

PMID- 8530284
TI  - Migraine with aura as the presentation of leukemia.
AB  - We present the case of a man with new onset of migraine with aura as the
      presenting sign of acute promyelocytic leukemia and disseminated intravascular
      coagulation. This previously unreported association may support theories of
      platelet serotonin involvement in the pathogenesis of migraine. It would be
      valuable in the future to evaluate other patients with disseminated intravascular
      coagulation or acute promyelocytic leukemia for the presence of migrainous auras
      or headaches, symptoms which may be underreported by patients, particularly in
      the setting of severe illness.

PMID- 8530285
TI  - Genesis of migraine without aura.

PMID- 8530286
TI  - Intranasal lidocaine.

PMID- 8530287
TI  - Cremation (Scotland) regulations 1935 (as amended) Form B--certificate of medical
      attendant Form C--confirmatory medical certificate.
AB  - It is important that doctors completing Forms B and C are fully aware of their
      statutory duties and responsibilities as laid down in the relevant cremation
      regulations. These forms should only be completed when the doctors concerned are
      confident that the information they are providing is true and accurate and that
      they have no reasonable cause to suspect that the decreased died either a violent
      or an unnatural death, or a sudden death of which the cause is unknown, or died
      in such a place or circumstances as to make further inquiry desirable before
      cremation. It should also be noted that medical referees have the statutory right
      to reject forms which are incomplete, or improperly completed.

PMID- 8530288
TI  - Post traumatic stress--RAF Hospital, Wegberg, Germany.

PMID- 8530289
TI  - Preliminary study into the opinions of patients about the presence of medical
      students in the general practice consultation.

PMID- 8530291
TI  - The role of the health service ombudsman.

PMID- 8530290
TI  - The Scottish Intercollegiate Guidelines Network Initiative: getting validated
      guidelines into local practice.

PMID- 8530292
TI  - Nuffield Centre for Community Care Studies.

PMID- 8530293
TI  - Community care in Scotland: progress from a community care implementation unit
      perspective.
AB  - Of necessity, this account of progress has been presented in summary form and has
      related to the particular focus of the CCIU's work. Significant progress has been
      achieved in many respects and many of the initial teething problems have been
      overcome. However, there is scope for improvement in the delivery of quality
      services for vulnerable people in our communities as we strive to offer real
      choice to them and their families in the provision of community care. Achieving
      this will be assisted greatly by agencies getting better at developing and
      implementing jointly their strategic thinking, working more closely on the
      'joins' in the system and recognising the strengths of other players.

PMID- 8530294
TI  - An assessment of antibiotic therapy of urinary tract infection in elderly,
      hospitalised patients.
AB  - The aim of the study was to compare the antibiotic treatment actually received by
      elderly, hospitalised patients with urinary tract infection (UTI) with 'optimal'
      therapy (as gauged by compliance with antibiotic policy, infecting organism,
      sensitivity data, patient renal function and cost). UTI was more common in
      females and in catheterised patients and E.Coli was the commonest pathogen.
      Trimethoprim and co-amoxiclav were the drugs used most frequently for either
      empirical or sensitivity data-based treatment. In 96% of infections a drug with
      appropriate action was administered. Often, however, treatment could have been
      optimised by substituting a cheaper suitable antibiotic, by standardising
      duration of therapy and ensuring that doses were adjusted for renal impairment.
      Savings from the use of 'optimal' therapy were estimated at 17%. There is clearly
      considerable scope for positive input from the clinical pharmacist in this area.

PMID- 8530295
TI  - A comparison study of day hospital and day centre attenders.
AB  - There has been much recent debate on the appropriateness and relative roles of
      the two main forms of day care available for dementia sufferers (day hospitals
      and day centres). The characteristics of day care attenders are an important
      aspect of this debate and have been examined in this study. The area surveyed
      (North Edinburgh) is unusual not only in respect of the relatively high number of
      day centre places but also in respect of the close working relationship between
      day centre and day hospital staff. Current data indicates that many of the
      attenders at day hospitals and day centres have similar characteristics
      suggesting that much of the work currently done in day hospitals could be done in
      day centres, and that even in North Edinburgh there is room for a further
      expansion in day centre places. Such expansion should not be wholly at the
      expense of day hospital services as not only are they providing, almost
      exclusively, a service for the most severely affected, but there is evidence that
      a small number of day centre attenders would benefit from a multi-disciplinary
      assessment such as the day hospital provides. For the two services to work
      effectively close liasion between workers, such as already exists in North
      Edinburgh, is a prerequisite.

PMID- 8530296
TI  - Trends in elderly patients (65 and over) waiting for long stay care in Edinburgh
      general hospitals 1988-1994.
AB  - Five surveys carried out in Edinburgh nonpsychiatric general hospitals between
      1988 and 1994 have shown a progressive drop in the number of elderly patients (65
      and over) waiting for long stay care. The overall point prevalence rate has
      fallen from 21.2% in 1988 to 9.2% in 1994. All three specialty categories
      (Geriatric Assessment, Geriatric Orthopaedic and General Medical) which have high
      prevalences have shown falls with the largest fall occurring in General Medical
      beds from 13.4% in 1988 to 3.8% in 1994. A substantial percentage (61.6%) of
      patients surveyed in 1994 were waiting to go into Private Nursing Homes which is
      in stark contrast to 8.5% in 1988, whereas the reverse has happened with those
      waiting for NHS Geriatric Long Stay care falling from 75% to 12.8%. It appears
      that the Community Care legislation has accelerated the shift toward Private
      Nursing Home care but has not, as feared, increased the number of old people
      waiting for long stay care in Edinburgh hospitals. The number of elderly patients
      awaiting long stay care in acute general medical beds in Edinburgh has now
      reached acceptable levels. If the same trend is occurring elsewhere in Scotland,
      we believe that attention should now turn to monitoring inappropriate early
      discharge of elderly patients.

PMID- 8530297
TI  - Post-mortem rates and junior doctors in Tayside--three years after the Joint
      Working Party report.
AB  - The total number of post-mortem examinations performed in Ninewells Hospital,
      Tayside's principal teaching hospital has fallen progressively over the last nine
      years despite publication in 1991 of the Joint Working Party report, 'The Autopsy
      and Audit'. There were 57% fewer autopsies carried out in 1994 than in 1986.
      Review of recent post-mortem rates in Ninewells Hospital, Dundee Royal Infirmary,
      Royal Victoria Hospital and Ashludie Hospital shows a wide variation and no ward,
      unit or hospital studied achieved rates adequate to satisfy the recommendations
      of the Joint Working Party report. A questionnaire sent to all Junior House
      Officers in Tayside in July 1994 showed that the Working Party report's clinical
      recommendations relating to junior medical staff concerning training to seek
      permission for autopsies, responsibility for obtaining permission for autopsies
      and attendance at the post-mortem room have not been implemented. Urgent
      implementation of the Joint Working Party reports clinical recommendations is
      called for to prevent clinical post-mortem examinations becoming obsolete.

PMID- 8530298
TI  - Motorcycle accidents in Strathclyde Region, Scotland during 1992: a study of the
      injuries sustained.
AB  - The purpose of this study was to describe the pattern and severity of injury,
      among motorcyclists involved in RTAs, in Strathclyde Region, Scotland, during
      1992. This information was required to provide insight into the nature of
      motorcycle accidents and their consequences, as well as to provide a basis for
      work on preventive measures. Ninety-six motorcyclist casualties were studied
      using police and medical information. Their injury information was coded
      according to AIS 90 and some descriptive statistics applied. Most of the
      casualties were young and most of them sustained more than one injury. Eight of
      the casualties died. The legs, arms, head and thorax were the body regions most
      commonly injured. Serious injury to one or both of the latter two regions,
      appeared to be implicated in the fatal outcomes. This study confirms that
      motorcycling is a 'high risk activity', and for those who wish to take that risk,
      protective measures of optimum standard should be regarded as priority.

PMID- 8530299
TI  - Accuracy of ICD-9 coding with regard to childhood accidents.
AB  - This paper documents deficiencies in ICD-9 coding which may influence the
      generation of statistics with regard to accident prevention. Problem areas are
      highlighted and remedial action suggested.

PMID- 8530300
TI  - No adverse effects on growth seen in Scottish school children consuming either
      low fat diets or diets relatively high in non-starch polysaccharide.
AB  - This paper reports whether diets relatively high in non-starch polysaccharide
      (NSP) or those which meet Dietary Reference Values for percentage energy from fat
      are associated with poor growth and anthropometric status. Children aged seven to
      eight years (n = 136) were recruited from five schools in and around Edinburgh,
      selected randomly by Lothian Region's Education Department. Dietary intakes were
      estimated by their parents, using the seven day weighed inventory method. Height
      and weight were measured twice, with an interval of approximately 12 months, and
      expressed as standard deviation scores of 1990 UK population standards. There
      were no significant differences in mean height, weight, body mass index and
      height velocity between those children whose diets were relatively high in NSP or
      low in percentage energy from fat compared to the remainder of the sample. In
      addition, using multiple regression analysis, no associations were seen between
      growth and low fat diets or between growth and higher fibre diets. These results
      suggest that the low fat, higher fibre message can be applied to young children.
      However, further research is required to ensure that the results found in this
      sample apply to other groups of children.

PMID- 8530301
TI  - The prevalence and pattern of disability in Scotland.

PMID- 8530302
TI  - The chief scientist reports ... Research notes.

PMID- 8530303
TI  - Early defibrillation and the role of automated external defibrillators.

PMID- 8530304
TI  - Header cracks related to reprocessing of single-use hemodialysis dialyzers.

PMID- 8530306
TI  - Potential for inadvertent pacing with Zoll PD 1200
      defibrillator/monitor/pacemakers.

PMID- 8530305
TI  - Design of Zoll defibrillators can result in failure to deliver defibrillation
      energy.

PMID- 8530307
TI  - ST-segment distortion in manual report mode of electrocardiographs.

PMID- 8530308
TI  - [Botulinus toxin therapy].

PMID- 8530309
TI  - [ENT anesthesia: the German Society of Anesthesia and Intensive Care Medicine on
      the use of succinylcholine].

PMID- 8530310
TI  - [Necrotizing sialometaplasia of the nasal cavity].

PMID- 8530311
TI  - [Therapy of Frey syndrome with botulinum toxin A. Experiences with a new method
      of treatment].
AB  - The effectiveness of botulinum toxin for the treatment of Frey's syndrome is
      demonstrated. Since December 1993, 14 patients with severe symptomatic gustatory
      sweating have been treated at the ENT Department, University of Gottingen.
      Botulinum toxin A (approximately 0.5 U/cm2) was injected intracutaneously into
      the affected skin area as determined by Minor's starch iodine test. Gustatory
      sweating in the treated skin area ceased completely within 2 days and did not
      reappear during the period of following (13 months maximum follow-up). There were
      no side effects. Findings show that local botulinum toxin injections are a highly
      effective, safe and minimally invasive treatment for Frey's syndrome. Moreover,
      this could be a new therapeutic tool for other forms of hyperhidrosis.

PMID- 8530313
TI  - [The technical safety of tissue expander domes].
AB  - Since leakage of an expander dome is a well-known complication that may lead to
      interruption of a tissue expansion procedure, the aim of this project was to
      study different expansion domes in relation to a medication port after
      perforation with various needles. MATERIAL AND METHODS: The combinations of five
      different expansion domes and one medication port were tested with three
      different needle types having two different diameters. The force-distance curves
      during puncturing, the puncture forces required and the leakage opening pressures
      were measured after single on repeated punctures with small and large forces. A
      total of more than 2000 experiments were performed. RESULTS: Only one of the
      expander domes and the medication port had sufficient pressure stability. The
      technical characteristics of these devices are presented. However, the different
      needle types and puncture techniques had only a minor influence on the pressure
      stability of the expander domes.

PMID- 8530312
TI  - [Do employees in the rubber industry have an increased risk of laryngeal
      cancer?].
AB  - Blue collar workers in the rubber industry are exposed to a number of toxic and
      potentially carcinogenic substances. In the last years an increased incidence of
      laryngeal cancer has been found in this group of workers. Besides naphthylamine,
      asbestos, vulcanization fumes and especially nitrosamines have been considered as
      possible causative agents. The present paper reviews the most relevant
      epidemiological studies on this topic published within the last 12 years and
      includes 17 cohort studies and 5 cases control studies. Only some of these papers
      indicate an increased risk for head and neck cancer due to employment in the
      rubber industry. Further in most studies the reported standard mortality ratios
      or relative risk ratios were not increased significantly. In nearly all of these
      studies an adjustment was not made for alcohol and tobacco consumption to
      compromise findings.

PMID- 8530314
TI  - [Significance of Staphylococcus aureus in nose operations. Risk of toxic shock
      syndrome?].
AB  - In a prospective clinical trial the pre- and postoperative presence of S. aureus
      was examined in 130 patients undergoing nasal septal surgery. The patients were
      randomized into three groups. The first group received no perioperative
      antibiotics, the second group was given oral amoxicillin plus clavulanic acid,
      while the third group was treated with oral sulfamethoxazol and trimethoprim. A
      significant decrease in the incidence of S. aureus was observed in post-operative
      cultures, but the difference was not attributable to the antibiotic use. Overall,
      18.9% of the S. aureus carriers harbored toxic shock syndrome toxin-1 positive
      strains. However, the decrease in the presence of S. aureus and the risk for
      toxic shock syndrome was not influenced by the antibiotics administered. These
      findings show that the routine use of oral prophylactic antibiotics for patients
      undergoing nasal surgery seems not indicated.

PMID- 8530315
TI  - [Pneumolabyrinth. Radiologic sign of perilymph fistula].
AB  - Post-traumatic cochleo-vestibular symptoms can be caused by peri-lymph fistulas,
      although these cannot be proven preoperatively in most cases by direct clinical
      examination. A rare case of a traumatic burst fracture of the promotory wall with
      a consequent perilymph fistula is presented. A preoperative computed tomographic
      finding of air in the basal turn of the cochlea and superior semicircular canal
      (pneumolabyrinth) is a reliable sign of perilymph fistula and justifies operative
      exploration for closure of the fistula. High-resolution computer tomographic
      imaging of the petrous bones in patients with post-traumatic cochleo-vestibular
      disturbances is mandatory.

PMID- 8530316
TI  - [Jugular vein thrombosis as incidental ultrasound finding in tumor patients].
AB  - At present thrombosis of the internal jugular vein is an uncommon event that is
      now more frequently associated with diagnostic or therapeutic catheterization. If
      an apparent spontaneous thrombosis occurs, malignancy should be considered in the
      differential diagnosis. Two cases of clinically asymptomatic thrombosis of the
      internal jugular vein are presented. A 69-year-old female patient with
      metastasizing renal cell carcinoma had bilateral thrombosis and a 73-year-old
      male with a small laryngeal carcinoma had a unilateral thrombosis. Increased
      blood coagulability as part of a paraneoplastic syndrome was considered to be the
      possible etiology. The role of sonography in the diagnosis is emphasized.

PMID- 8530317
TI  - [Heart arrest in children after intravenous injection of succinylcholine in the
      ENT operating room].
AB  - Acute rhabdomyolysis with hyperkalemia has been followed by ventricular
      dysrhythmia, cardiac arrest and death after the administration of succinylcholine
      to apparently healthy children who were subsequently found to have undiagnosed
      skeletal muscle myopathies. Boys have mostly been affected. Reports of anesthesia
      emergencies from the United States and Germany have indicated that serious side
      effects of succinylcholine are not as rare as previously thought. This disorder
      often presents as sudden cardiac arrest within minutes after the administration
      of the drug. The tragedy is that an apparently healthy child dies abruptly during
      what was considered to be a relatively uncomplicated surgical procedure (most
      often in ENT surgery). Due to the abrupt onset of rhabdomyolysis, routine
      resuscitative measures are likely to be unsuccessful. Extraordinary measures
      (including institution of extracorporeal circulation) and prolonged efforts have
      resulted in successful resuscitation of some cases. Since there are usually no
      signs or symptoms to alert the practitioner to patients at risk, the use of
      succinylcholine in children should be reserved for emergency intubations or
      instances in which immediate securing of the airway is necessary.

PMID- 8530318
TI  - [Diagnosis and therapy of salivary gland tumors. II].

PMID- 8530319
TI  - Fragmentation and narcissism. A revaluation.
AB  - The paper focuses on the articulation of two areas of theory: that of development
      of the self through fragmentation and differentiation and that of narcissism in
      early psychological development, and its pathology later in life. Jungian ideas
      concerning the self and individuation (including those developed by Fordham) are
      linked with psychoanalytic ideas, notably Kohut's, and related to the concepts of
      narcissism and ego-development. In this the focus is on a revaluation of the
      negative overtones of 'fragmentation' and 'narcissism' and an indication of their
      place in the process of individuation. It is pointed out that a varying emphasis
      in the analyst on what are called the biological and ethological aspects of these
      theories will have important implications for the treatment of patients. The
      theoretical position is illustrated by a lengthy clinical example involving a
      case of early injury to the self which suggests the pathology of narcissistic
      character disorder. But the case also illustrates the contribution to development
      of fragmentation and narcissism, which are revalued here as the 'part-for-the
      whole' and as one of the 'motors' of individuation. Working within a perspective
      that prioritizes the importance of the drive towards relationship, it is
      recommended that the analyst learns to respect and value phenomenologically the
      contribution of fragmentation and narcissism to normal development, if true
      healing is to occur.

PMID- 8530320
TI  - New collateral flow increasing early after coronary occlusion prevented
      myocardial necrosis in dogs.
AB  - Increases in regional myocardial blood flow (Qm) developing soon after myocardial
      infarction may minimize myocardial necrosis. To test this hypothesis, Qm in the
      area surrounding an acutely occluded coronary artery was determined successively
      over 4 weeks in 11 dogs. Non-radioactive colored microspheres were injected into
      the left atrium 5 s (Qm at this time is referred to as Q1), 3 h (Q2), 12 h (Q3),
      and 4 weeks (Q4) after occlusion of the coronary artery. After termination of the
      experiment, the heart was removed, and Qm and three indices of myocardial
      necrosis i.e., myocardial creatine kinase activity (CK), infarct size determined
      by triphenyl tetrazolium chloride stain (TTC), and myocardial fibrosis visualized
      by Azan-Mallory stain, were determined. Each Qm was expressed as a percentage of
      normal: Qm (% of normal) = [Q/Qc] ischemic area/[Q'/Qc']non-ischemic area x 100,
      where Qc indicates Qm determined before coronary occlusion. In the ischemic area
      of the left ventricle, Q1, Q2, Q3, and Q4 were 25 +/- 3%, 30 +/- 3%, 31 +/- 3%,
      and 42 +/- 3% of normal, respectively, in the inner layer, and 31 +/- 3%, 52 +/-
      4%, 52 +/- 4%, and 77 +/- 6% of normal, respectively, in the outer layers. During
      the 4-week period, the increase of Qm in the outer layer was greater than that in
      the inner layer. The inner layer showed a small increase of flow from Q3 to Q4 (9
      +/- 2%), but in the outer layer there were greater flow increases from Q1 to Q2
      (21 +/- 3%) and from Q3 to Q4 (24 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8530321
TI  - Vitamin E prevents endothelial injury associated with cisplatin injection into
      the superior mesenteric artery of rats.
AB  - To clarify the pathogenesis of the vascular injury caused by the administration
      of anti-neoplastic drugs, cisplatin with lipiodol was infused into the superior
      mesenteric artery of rats. Morphological and biochemical changes in the vascular
      wall and the prophylactic effects of vitamin E were examined 4 days after
      administration. In the cisplatin-treated group, but not in the other groups,
      severe endothelial injury, such as vacuolation, subendothelial edema, and
      destruction of the internal elastic membrane, was observed. Superoxide dismutase,
      a potent scavenger of the superoxide anion, was markedly lower in the cisplatin
      group, and Na/K-ATPase, a marker of the plasma membrane, was also low in this
      group. These morphological changes were minimal, and enzyme activity was higher
      in the vitamin E-treated group than in the cisplatin-treated group. These
      findings indicate that endothelial injury after cisplatin administration could be
      caused by free radical-induced lipid peroxidation of the membrane system, and
      that such injury may be prevented by the co-administration of vitamin E.

PMID- 8530322
TI  - Sotalol facilitates spontaneous ventricular defibrillation by enhancing
      intercellular coupling. An entirely new mechanism for its antiarrhythmic action.
AB  - We have previously shown that sotalol, a class III antiarrhythmic agent, helps
      spontaneous ventricular defibrillation in various mammalian species. Since we
      hypothesized that self ventricular defibrillation depends on a high degree of
      intercellular synchronization, and since the major electrophysiological action of
      sotalol causing prolongation of action potential duration (APD), cannot fully
      explain its defibrillating property, we carried out a series of studies to
      examine the effect of sotalol on intercellular myocardial coupling. Guinea pig
      right ventricular muscle preparations were superfused in a tissue bath and the
      spread of intracellularly injected fluorescent dye (Lucifer yellow CH) to the
      neighboring cells was studied under various conditions. When either the Ca2+
      concentration of Tyrode's solution was elevated to 6 mM or the solution was made
      hypoxic by not bubbling O2 (n = 3 each), no spread of the injected dye was
      observed. The addition of 1 microM sotalol to the high Ca2+ solution or 0.5
      microM to the hypoxic superfusate (n = 3 each) caused a wide spreading of the
      dye, thus strongly suggesting a marked improvement in the intercellular coupling.
      These results show an entirely new property of sotalol, i.e., enhancement of
      cellular synchronization, which may better explain its ability to cause
      spontaneous ventricular defibrillation than its class III action. Our previous
      demonstration of successful spontaneous ventricular defibrillation by several
      other agents that are known to enhance intercellular coupling but have
      contrasting actions on APD further substantiates our hypothesis.

PMID- 8530323
TI  - Mechanisms of coronary hyperconstriction in response to serotonin induced by X
      irradiation in miniature pigs: increased constrictive response of medial smooth
      muscle.
AB  - Experimental and clinical studies suggest that X-irradiation to the coronary
      artery may enhance vasoconstrictive response. This study aimed to clarify the
      effect of X-irradiation on the vasomotor response of porcine coronary artery. X
      ray (15 Gy) was selectively irradiated to the left anterior descending coronary
      artery (LAD) in 14 Gottingen miniature pigs. The coronary vasomotor responses to
      serotonin at the irradiated site (LAD) and the control site (the left circumflex
      artery; LCX) were assessed by quantitative arteriography before and 1 h and 1, 2,
      and 4 weeks after X-irradiation. At 2 weeks, endothelium-dependent vasodilation
      in response to substance P was also evaluated arteriographically in vivo. At 2
      weeks, isometric tension studies were performed to evaluate the constrictive
      responses of medial muscle strips and endothelium-dependent relaxation. Coronary
      vasoconstriction in response to serotonin was enhanced 1 week after, and further
      augmentation was noted 2 and 4 weeks after X-irradiation. Endothelium-dependent
      vasodilation in response to substance P in vivo was preserved 2 weeks after X
      irradiation. Coronary arteriography showed no organic stenosis at the irradiated
      site. In vitro studies demonstrated that medial muscle strips of the irradiated
      site showed hypercontraction in response to serotonin and that endothelium
      dependent relaxation in response to serotonin and substance P was preserved at
      the irradiated site. A histological study revealed no appreciable changes of the
      endothelial cells or intimal thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8530324
TI  - Pregnancy-induced alterations of relaxation in response to magnesium in the rat
      aorta may be due to plasma-borne agents.
AB  - The influence of plasma from pregnant and nonpregnant humans was examined, using
      magnesium-induced relaxation of precontracted rat aortic rings. The results
      showing magnesium-induced relaxation of aortic rings from pregnant and
      nonpregnant rats were compared. In rat aortic rings incubated in plasma from
      pregnant patients, magnesium was more potent in relaxing the precontractions
      induced by potassium chloride than in relaxing those induced by phenylephrine.
      The magnesium-induced relaxation of rings incubated in plasma from normal
      pregnant subjects was similar to that in unincubated rings from normal pregnant
      rats. Neither the removal of endothelium nor pretreatment with indomethacin
      affected the pattern of responses in the rings. The results suggest that the
      effects of pregnancy on magnesium-induced relaxation of the rat aorta may be
      mediated by plasma-borne agents, and the mechanisms by which the agents alter the
      relaxation do not involve either the vascular endothelium or prostaglandin
      synthesis.

PMID- 8530325
TI  - Detection and localization of early diastolic forces within the left ventricle
      from inflow jet dynamics. A comparison between normal subjects and patients with
      dilated cardiomyopathy.
AB  - We studied the properties of the jet of blood entering the left ventricle from
      the left atrium during early diastole in 32 patients with dilated cardiomyopathy,
      and 24 normal subjects of similar age. The diameter of the jet was measured from
      the cross-sectional color Doppler image and its cross-sectional area (JA) was
      derived. Pulsed Doppler records of flow velocity were made at 1-cm intervals into
      the ventricle from the mitral ring. Peak (Vp) and mean (Vm) E wave velocity and
      time velocity integral (TVI) were determined. At any level in the ventricle,
      therefore, the early diastolic volume of blood remaining in the jet, i.e., the
      flow time integral, is given by JA.TVI; the local flow rate, Q, by JA.Vm; and jet
      momentum along the long axis of the ventricle by Q.Vp. In normals, the jet cross
      sectional area fell from 5.9 (1.3) cm2 at the mitral ring to 4.9 (0.7) cm2 at 4
      cm (P < 0.05), but the flow time integral fell proportionately more, from 46.0
      (15.2) ml at the ring level to 15.9 (3.4) ml at 4 cm (P < 0.01). Axial momentum
      flux was 44 (13) x 10(2) cm4s-2 at the ring level, falling to 28 (10) x 10(2)
      cm4s-2 at 4 cm (P < 0.01). In dilated cardiomyopathy, the jet cross-sectional
      area was much smaller than normal, 1.9 (0.8) cm2 at the ring level, and it
      remained effectively constant, being 2.0 (0.9) cm2 at 6 cm (P < 0.01 vs
      normals).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8530326
TI  - Selective right ventricular angiography in apparently idiopathic ventricular
      fibrillation.
AB  - The definition of underlying heart disease in apparently idiopathic ventricular
      fibrillation seems to be important in regard to prognosis and choice of therapy.
      From October 1989, until August 1993, cardiac arrest due to the documented
      ventricular fibrillation occurred in eight consecutive patients with normal
      results on clinical examination, normal echocardiography, and normal or
      apparently nonspecific electrocardiogram (ECG) findings. Complete invasive
      investigations, including selective right ventricular angiography, were done;
      regional hypokinesia and segmental bulging of the right ventricle were found in
      seven patients (88%). Arrhythmogenic right ventricular dysplasia was suspected in
      these patients, although endomyocardial biopsy was not performed. After the
      finding of localized right precordial QRS prolongation of more than 110 ms in
      November 1993 in five patients, a retrospective, a more precise approach to QRS
      duration in standard ECG supported this diagnosis. Selective right ventricular
      angiography is of great help in identifying underlying heart disease in patients
      with apparently idiopathic ventricular fibrillation, and confirms ECG findings.

PMID- 8530327
TI  - Diagnosing infection of extracardiac conduit in children.
AB  - Between August 1985 and July 1992, at our center, 142 Japanese children had an
      extracardiac conduit operation to reconstruct the right ventricular outflow
      tract. The study group consisted of 22 of these 142 children who had a persistent
      fever and whose serum was positive for acute-phase reactants after the operation.
      We present the diagnostic findings for 10 children with infection of an
      extracardiac conduit that had been placed to restore the continuity of the right
      ventricle-pulmonary artery. They were part of the group of 22 children who were
      followed over the past 7 years with blood cultures, echocardiography, and 67Ga
      imaging. All 10 developed a persistent fever and were seropositive for acute
      phase reactants. Conduit infection was diagnosed in only 2 patients by the
      detection of vegetation on echocardiography and was diagnosed in 9 of the 10
      patients by an abnormal 67Ga uptake in the area of the artificial vessels used to
      reconstruct the pulmonary artery. The present study compared the use of blood
      cultures, echocardiography, and 67Ga imaging in diagnosing an infection of the
      extracardiac conduit. The sensitivity of blood cultures in diagnosing an
      extracardiac conduit infection was 70% (7/10), and the specificity was 92%
      (1/12). 67Ga imaging showed a higher sensitivity than echocardiography in
      diagnosing infection of an extracardiac conduit.

PMID- 8530329
TI  - Apical hypertrophy associated with rapid T wave inversion on the
      electrocardiogram.
AB  - A 53-year-old man who had no chest pain and no family history of heart disease
      demonstrated a rapid T wave change on an electrocardiogram, from a positive T
      wave to a giant negative T wave, within 1 year. Echocardiography showed no left
      ventricular hypertrophy before or after the T wave change. Cine-magnetic
      resonance imaging revealed focal apical hypertrophy after the appearance of the
      giant negative T wave. Although T wave inversions sometimes develop within a
      short period in patients with hypertrophic cardiomyopathy, they are rare in a
      patient without hypertension or chest pain.

PMID- 8530328
TI  - A rare case of large ventricular septal defect with minimal pulmonary vascular
      obstructive changes in a 41-year-old woman.
AB  - We describe a case of large ventricular septal defect (VSD) with minimal
      obstructive changes in the small pulmonary arteries of a 41-year-old woman.
      Before cardiac catheterization, some laboratory findings led us to consider that
      surgical closure of the defect would not be possible. However, because
      hemodynamic examinations showed only mildly elevated pulmonary vascular
      resistance, we patch-closed the VSD successfully. The histology of lung specimens
      showed only minimal obstructive changes in the small pulmonary arteries.
      Considering the size of the VSD and the age at which we hemodynamically evaluated
      the patient, the mildness of the pulmonary vascular obstructive changes appeared
      to be atypical in the natural course of a VSD of this size.

PMID- 8530330
TI  - The effects of substance use disorder on the clinical presentation of anxiety and
      depression in an outpatient psychiatric clinic.
AB  - BACKGROUND: The comorbidity of substance abuse or dependence and psychiatric
      illness can complicate the diagnosis, clinical course, and treatment of dually
      diagnosed patients. In this study, we examined the relationship between substance
      use disorder (SUD) and psychopathology in an outpatient psychiatric setting.
      METHOD: Among 391 patients evaluated at an anxiety and effective disorders
      clinic, 54 patients met DSM-III-R criteria for lifetime substance use disorder
      and current unipolar depression or anxiety disorder. We selected 54 sex- and age
      matched controls with psychiatric illness without SUD as a comparison group. All
      patients were given a structured diagnostic interview and symptom rating scales.
      In addition to comparing dual and single diagnosis groups, we compared those
      within the dual diagnosis group and those with primary psychiatric disorder with
      those with primary SUD; we also compared those with current versus past SUD.
      RESULTS: In contrast to findings in other settings, there were no significant
      differences in the severity of psychopathology between patients with and without
      substance abuse/dependence. Within dually diagnosed patients, those with primary
      mental disorder were more anxious and depressed than those with primary SUD.
      Patients with primary mental disorder had a significantly higher number of
      psychiatric diagnoses, an earlier onset of any psychiatric disorder, and were
      more likely to have received treatment. Conversely, patients with primary SUD had
      a higher number of substance use disorder diagnoses and an earlier onset of SUD.
      CONCLUSION: Dually diagnosed patients had the same degree of psychopathology as
      patients with only psychiatric disorders in this outpatient psychiatric
      population. The primary/secondary classification may be useful to distinguish
      between subgroups of dual diagnosis patients. Future studies are necessary to
      determine if this distinction can be useful to predict course and outcome in
      dually diagnosed patients.

PMID- 8530331
TI  - Risperidone versus clozapine in the treatment of psychosis in six patients with
      Parkinson's disease and other akinetic-rigid syndromes.
AB  - BACKGROUND: We report six cases of psychosis in patients with akinetic-rigid
      syndromes who were treated with risperidone. RESULTS: Five of the six patients
      experienced intolerable exacerbation of parkinsonism. Four subsequently did well
      on clozapine therapy. One patient required nursing home placement and a feeding
      gastrostomy as a result of the worsening parkinsonism during risperidone
      treatment, but was able to return home and have the gastrostomy removed after
      switching from risperidone to clozapine. Two of the five patients who worsened
      motorically also developed encephalopathy during risperidone treatment; the
      encephalopathy resolved when the patients were switched to clozapine treatment.
      Only one patient, the youngest, did well on risperidone therapy. CONCLUSION: We
      believe that risperidone is not a substitute for clozapine in treating psychosis
      in parkinsonian patients and should be used with caution.

PMID- 8530332
TI  - Personality traits in social phobia, I: Comparisons with healthy controls.
AB  - BACKGROUND: Patients with social phobia often describe a general interpersonal
      sensitivity and meet criteria for DSM-III-R avoidant personality disorder. This
      study addresses the question of whether patients with social phobia have
      characteristic abnormal personality traits. METHOD: A questionnaire with 140
      items for self-rating personality traits was constructed for the study. Ratings
      obtained from 63 patients with social phobia were compared with ratings from 58
      healthy controls. Structured interviews were also conducted with the patients to
      establish whether their disorders met the criteria for the DSM-III-R avoidant
      and/or dependent personality disorders. RESULTS: Ninety-one items on the
      questionnaire were rated significantly (p < .01) differently by the patients and
      the controls. These items were divided into two item-groups, one relating to
      avoidant social behavior (subdivided by factor analysis into six factors) and
      another relating to more general depressive-anxious traits (five factors). The
      total scores had a normal distribution among the patients. With the 95th
      percentile of the controls as the cutoff point, only 22% of the patients had a
      total score within normal limits on avoidant social behavior. Avoidant
      personality disorder was diagnosed in 60% of the patients. CONCLUSION: The
      results support the hypothesis that patients with social phobia generally have
      characteristic abnormal personality traits, but lend no support to a division of
      the symptoms and traits into two separate diagnoses.

PMID- 8530333
TI  - Personality traits in social phobia, II: Changes during drug treatment.
AB  - BACKGROUND: Patients with social phobia often describe personality traits
      characterized by avoidant social behavior and more general depressive-anxious
      features. There is only sparse knowledge about the effects of drug treatment on
      these traits. METHOD: Fifty-seven patients with social phobia completed a 12-week
      double-blind, placebo-controlled trial with the reversible and selective
      monoamine oxidase A inhibitor brofaromine 150 mg/day. The Clinical Global
      Impressions-Improvement scale, Liebowitz Social Anxiety Scale, a questionnaire
      with 140 items regarding personality traits, and ratings on the presence or
      absence of diagnostic criteria for the DSM-III-R avoidant and dependent
      personality disorders were used for assessments at baseline and endpoint.
      Comparisons were made with a group of 58 healthy controls. RESULTS: Before
      treatment, there were no significant differences between the brofaromine and
      placebo groups in their ratings on situationally bound social anxiety or on
      personality traits that differed significantly from those of the controls. At
      endpoint, a marked normalization was noted in the brofaromine group. The changes
      that had occurred differed significantly from those in the placebo group. The
      normalization of traits seemed more marked than the normalization of anxiety in
      more specific social phobic situations. The number of brofaromine patients who
      fulfilled the criteria for avoidant personality disorder had diminished from 15
      (60%) to 5 (20%). CONCLUSION: The results support the conclusion that the
      maladaptive personality traits characteristic of social phobia are at least as
      responsive to the monoamine oxidase inhibitor brofaromine as are the more
      circumscribed social anxiety responses.

PMID- 8530334
TI  - Cardiovascular safety in depressed patients: focus on venlafaxine.
AB  - BACKGROUND: Cardiovascular side effects from antidepressant drugs, including
      clinically significant blood pressure changes, conduction disturbances, and
      arrhythmias may complicate long-term therapy. Cardiovascular effects are most
      common with tricyclic antidepressants, but occur rarely with most
      antidepressants. Venlafaxine is a unique antidepressant with a broad spectrum of
      antidepressant activity and a safety profile that resembles serotonin selective
      reuptake inhibitors. METHOD: A MEDLINE search of the literature in the English
      language for the past 15 years was conducted, and the venlafaxine new drug
      application data base was reviewed. RESULTS: Clinically significant conduction
      abnormalities or arrhythmias have not been reported with venlafaxine; however,
      this drug has not been studied in patients with underlying cardiovascular
      disease. A dose-related increase in mean blood pressure has been observed. In
      placebo-controlled studies with venlafaxine, clinically significant increases in
      blood pressure (increase in diastolic blood pressure of > or = 15 mm Hg and to >
      or = 105 mm Hg from baseline) were observed in 5.5% of patients at doses above
      200 mg daily. The mean increase in diastolic blood pressure was 7 mm Hg after 6
      weeks of treatment with doses of 300 to 375 mg daily. In comparative trials, the
      overall incidence of clinically significant blood pressure increases with
      venlafaxine was similar to that of tricyclic antidepressants. CONCLUSION:
      Overall, venlafaxine has a low incidence of clinically significant increases in
      blood pressure at doses below 200 mg daily. As with other antidepressants that
      may affect blood pressure, the clinician should periodically monitor blood
      pressure in patients treated with venlafaxine.

PMID- 8530335
TI  - Self-injurious behavior: pathophysiology and implications for treatment.
AB  - BACKGROUND: Self-injurious behavior (SIB) is a common clinical problem that
      affects a diverse group of patients and populations. Little is known about the
      underlying pathophysiology and pharmacologic treatment of SIB. METHOD: The
      authors selectively reviewed the clinical literature on SIB and related
      aggressive/impulsive behaviors, with the aim of formulating provisional
      guidelines for pharmacotherapy. RESULTS: The serotonergic system is most directly
      implicated in the pathophysiology of SIB and related behaviors. While there is no
      well-established "drug of choice" for SIB, the identification of specific
      subgroups of SIB patients and associated symptoms such as psychosis permits the
      rational selection of medication. Serotonin selective reuptake inhibitors, other
      serotonergic agents, antipsychotics, beta-blockers, and opiate antagonists all
      play a role in the treatment of SIB. CONCLUSION: SIB is not a single entity and
      may have different pharmacologic treatments, depending on the associated symptoms
      and target population. Medications that act on the serotonergic system appear to
      be the most promising.

PMID- 8530336
TI  - Photosensitivity to clozapine.

PMID- 8530337
TI  - Severe myoclonus produced by fluvoxamine.

PMID- 8530338
TI  - Valproic acid for dysphoric mania in a mentally retarded adolescent.

PMID- 8530339
TI  - Provide fluoxetine information vital to clinicians.

PMID- 8530340
TI  - Sertraline for premature ejaculation.

PMID- 8530341
TI  - Development of drug resistance to HIV-1 protease inhibitors.

PMID- 8530342
TI  - The human gp39 promoter. Two distinct nuclear factors of activated T cell protein
      binding elements contribute independently to transcriptional activation.
AB  - gp39, a cytokine expressed on the surface of activated T cells, is essential for
      T cell-dependent antibody responses in vivo. We cloned and sequenced 1.2
      kilobases of the 5' flank region of the human gp39 gene promoter and determined
      its transcription start site. When used in reporter gene assays, this DNA segment
      conferred promoter activity in response to T cell activation. gp39 promoter
      function in transfectants was inhibited by cyclosporin A, as is expression of the
      endogenous gp39 gene in T-lineage cells. At least 0.5 kilobase of the 5' flank
      region was required for promoter activity. Two putative binding sites for the NF
      AT family of transcriptional activator proteins were identified at -259 to -265
      and -62 to -69 with respect to the transcription start site. Both sites
      contributed significantly and independently to promoter activity in response to T
      cell activation. Additionally, when incubated in vitro with nuclear protein
      purified from activated human CD4 T cells, both of these sites preferentially
      bound the NF-AT family member, NF-ATp. These results suggest that NF-ATp, via
      binding to at least two cis-elements, is essential for the induction of gp39 gene
      expression in response to T cell activation.

PMID- 8530343
TI  - Interaction of the transforming growth factor-beta type I receptor with farnesyl
      protein transferase-alpha.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is the prototype of a large family
      of molecules that regulate a variety of biological processes. The type I (T beta
      R-I) and type II (T beta R-II) receptors for TGF-beta 1 are transmembrane
      serine/threonine kinases, forming a heteromeric signaling complex. Recent studies
      have shown that T beta R-II is a constitutively active kinase and phosphorylates
      T beta R-I upon ligand binding, suggesting that T beta R-I is the effector
      subunit of the receptor complex, which transduces signals to intracellular
      targets. This model has been further confirmed by the identification of
      constitutively active T beta R-I that mediates TGF-beta 1-specific cellular
      responses in the absence of ligand and T beta R-II. To investigate signaling by
      TGF-beta 1, we have sought to isolate proteins that interact with the cytoplasmic
      region of T beta R-I. One of the proteins identified was the alpha subunit of
      farnesyl-protein transferase (FT alpha) that modifies a series of peptides
      including Ras. T beta R-I specifically interacts with FT alpha in the yeast two
      hybrid system. Glutathione S-transferase-T beta R-I fusion proteins bind FT alpha
      translated in vitro. T beta R-I also phosphorylates FT alpha. We further show
      that the constitutively active T beta R-I interacted with FT alpha very strongly
      whereas an inactive form of T beta R-I did not. These results suggest that FT
      alpha may be one of the substrates of the activated T beta R-I kinase.

PMID- 8530344
TI  - Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in
      the rapid degradation of CYP2E1.
AB  - In the present study, we demonstrate that ethanol induces CYP2E1 by protein
      stabilization in vivo. The control half-life of CYP2E1 was determined to be 6-7 h
      followed by a slower secondary phase. The half-life of ethanol-stabilized CYP2E1
      was calculated to be 38 h. The mechanism underlying the rapid degradation of
      CYP2E1 was also investigated and appears to involve the ubiquitin-proteasome
      proteolytic pathway. An in vitro assay using the cytosolic fraction was developed
      to further characterize CYP2E1 degradation. Using this assay, 40-50% loss of
      CYP2E1 was observed in 1 h, coincident with the formation of high M(r) ubiquitin
      CYP2E1 conjugates. At concentrations approximating those found in vivo, ethanol
      protects CYP2E1 from cytosolic degradation. No loss of CYP2B1/2 was observed
      under identical conditions, suggesting that this reaction is specific for certain
      P-450s which are rapidly turned over.

PMID- 8530345
TI  - Cooperative formation of higher order peroxisome proliferator-activated receptor
      and retinoid X receptor complexes on the peroxisome proliferator responsive
      element of the rat hydratase-dehydrogenase gene.
AB  - Peroxisome proliferator-activated receptor (PPAR) forms a heterodimer with
      retinoid X receptor (RXR) that binds to the peroxisome proliferator responsive
      element (PPRE) to regulate the expression of target genes. PPRE of the rat enoyl
      CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD) gene has previously been shown
      to consist of three imperfect TGACCT half-sites and form two distinct complexes
      (C1 and C2) with the nuclear extracts from H4IIEC3 cells. The present study
      identifies another imperfect TGACCT motif involved in the PPAR/RXR-mediated trans
      activation process and demonstrates that these four imperfect TGACCT motifs
      constitute an unique binding site consisting of two DR1 elements overlapping a
      DR2 element. PPAR and RXR cooperatively bind the two DR1 elements to form C1
      complex or bind DR2 element to form C2 complex with a 1:1 ratio. Saturation of
      the HD PPRE probes with receptor proteins cannot convert the heterodimeric C2
      complex to the higher order C1 complex, suggesting that they are formed
      independently. Transfection analyses indicate that mutation of any one of these
      TGACCT motifs or truncation of the entire HD PPRE into a separate DR1 and DR2
      element significantly reduced the transcriptional response of HD PPRE to
      peroxisome proliferators. The rat HD PPRE differentially binds with one or two
      PPAR/RXR heterodimers providing the peroxisome proliferator signaling pathway
      with two levels of response.

PMID- 8530346
TI  - Human ADP-ribosylation factor-activated phosphatidylcholine-specific
      phospholipase D defines a new and highly conserved gene family.
AB  - Activation of phosphatidylcholine-specific phospholipase D (PLD) has been
      implicated as a critical step in numerous cellular pathways, including signal
      transduction, membrane trafficking, and the regulation of mitosis. We report here
      the identification of the first human PLD cDNA, which defines a new and highly
      conserved gene family. Characterization of recombinant human PLD1 reveals that it
      is membrane-associated, selective for phosphatidylcholine, stimulated by
      phosphatidylinositol 4,5-bisphosphate, activated by the monomeric G-protein ADP
      ribosylation factor-1, and inhibited by oleate. PLD1 likely encodes the gene
      product responsible for the most widely studied endogenous PLD activity.

PMID- 8530347
TI  - Thimerosal interacts with the Ca2+ release channel ryanodine receptor from
      skeletal muscle sarcoplasmic reticulum.
AB  - The thiol-oxidizing reagent, thimerosal, has been shown to increase the
      intracellular Ca2+ concentration, to induce Ca2+ spikes in several cell types,
      and to increase the sensitivity of intracellular Ca2+ stores to inositol 1,4,5
      trisphosphate. Ryanodine-sensitive stores have also been implicated in the
      generation of Ca2+ oscillations induced by the addition of thimerosal. Here we
      report that micromolar concentrations of thimerosal stimulate Ca2+ release from
      skeletal muscle sarcoplasmic reticulum vesicles, inhibit high affinity
      [3H]ryanodine binding, and modify the channel activity of the reconstituted Ca2+
      release protein. Thimerosal inhibits ryanodine binding by decreasing the binding
      capacity (Bmax) but does not affect the binding affinity or the dissociation rate
      of bound ryanodine. Single channel reconstitution experiments show that
      thimerosal (100-200 microM) stimulates single channel activity without modifying
      channel conductance. The thimerosal-stimulated channel is not inhibited by
      heparin. Furthermore, a Ca(2+)-stimulated channel is first activated and then
      inhibited in a time-dependent fashion by high concentrations of thimerosal (1
      mM). Once inactivated, the channel cannot be reactivated by addition of either
      Ca2+ or ATP.

PMID- 8530348
TI  - Reconstitution of hairpin ribozyme activity following separation of functional
      domains.
AB  - The hairpin ribozyme is a 50-nucleotide RNA enzyme of unknown three-dimensional
      structure. Here, we, demonstrate that interdomain interactions are required for
      catalytic function by reconstitution of activity following separation of an
      essential, independently folding domain (loop B) from the substrate binding
      strand at a helical junction. The resulting construct relies on long range
      tertiary contacts for catalysis. For this work, we used an optimized ribozyme and
      substrate, which included sequence changes to minimize the formation of
      nonproductive conformational isomers. Kinetic analysis was carried out using both
      single and multiple turnover methods and shows that the catalytic efficiency
      (kcat/Km) of the reconstituted ribozyme is 10(4)-fold lower than that of the
      intact ribozyme. The decrease in kcat/Km results entirely from a 10(4)-fold
      increase in the apparent Km, whereas the kcat parameter is essentially unchanged.
      Therefore, cleavage chemistry appears to be unimpaired, but the reaction is
      limited by the productive assembly of the two domains. Our results strongly
      support a previously proposed model in which the catalytic topology of the
      ribozyme contains a bend at a helical junction.

PMID- 8530349
TI  - The inhibition mechanism of serpins. Evidence that the mobile reactive center
      loop is cleaved in the native protease-inhibitor complex.
AB  - Inhibitors that belong to the serine protease inhibitor or serpin family have
      reactive centers that constitute a mobile loop with P1-P1' residues acting as a
      bait for cognate protease. Current hypotheses are conflicting as to whether the
      native serpin-protease complex is a tetrahedral intermediate with an intact
      inhibitor or an acyl-enzyme complex with a cleaved inhibitor P1-P1' peptide bond.
      Here we show that the P1' residue of the plasminogen activator inhibitor type 1
      mutant (P1' Cys) became more accessible to radiolabeling in complex with
      urokinase-type plasminogen activator (uPA) compared with its complex with
      catalytically inactive anhydro-uPA, indicating that complex formation with
      cognate protease leads to a conformational change whereby the P1' residue becomes
      more accessible. Analysis of chemically blocked NH2 termini of serpin-protease
      complexes revealed that the P1-P1' peptide bonds of three different serpins are
      cleaved in the native complex with their cognate protease. Complex formation and
      reactive center cleavage were found to be rapid and coordinated events suggesting
      that cleavage of the reactive center loop and the subsequent loop insertion
      induce the conformational changes required to lock the serpin-protease complex.

PMID- 8530350
TI  - Release of gelatinase A (matrix metalloproteinase 2) induced by photolysis of
      caged phosphatidic acid in HT 1080 metastatic fibrosarcoma cells.
AB  - Phosphatidic acid (PA) is a putative novel messenger in signal transduction and
      membrane traffic. We have synthesized a photolyzable derivative of PA, termed
      caged PA (cPA), which may be utilized as a new tool in studies of PA-mediated
      cellular events. 1-(2-Nitrophenyl)diazoethane, synthesized from 2
      nitroacetophenone, was reacted with dipalmitoyl-PA to yield a 1-(2
      nitrophenyl)ethyl ester of PA. Photolysis of the compound by ultraviolet light
      resulted in the formation of phosphatidic acid. The structure of the compound and
      of its photolytic products was verified by NMR spectroscopy. The utility of cPA
      was examined in HT 1080 metastatic fibrosarcoma cells, in which the formation of
      PA by phospholipase D was implicated in laminin-induced release of gelatinase A
      (matrix metalloproteinase 2 (MMP-2)). The uptake of cPA by HT 1080 cells reached
      a plateau after 120 min of incubation. Ultraviolet illumination of cPA-loaded
      cells for 5 s resulted in photolysis of 1.8% of the cell-incorporated cPA. The
      photolysis of cPA caused a 2-fold elevation in the release of MMP-2 to the
      medium, whereas nonphotolyzed cPA caused no change in MMP-2 release. Moreover,
      the effect of cPA photolysis was significantly higher than that obtained with
      extracellularly introduced PA. Thus, the effect of laminin on MMP-2 secretion can
      be mimicked by photolysis of cPA, suggesting a pivotal role for phospholipase D
      in laminin-induced cancer cell invasiveness and metastasis. These results
      indicate that cPA could serve as a unique tool for studying the cellular roles of
      PA.

PMID- 8530351
TI  - Inhibition of ubiquitin-mediated proteolysis by the Arabidopsis 26 S protease
      subunit S5a.
AB  - A variety of protease inhibitors have been used to study ubiquitin-dependent
      proteolysis by the 26 S protease. However, these inhibitors lack complete
      specificity and thus affect ubiquitin-independent pathways as well. We recently
      identified an Arabidopsis protein, MBP1, that is homologous to subunit 5a (S5a)
      of the human 26 S protease complex. MBP1 and S5a bind multiubiquitin chains with
      high affinity and presumably facilitate the recognition of ubiquitin conjugates
      by the 26 S protease. We show here that free MBP1 can be a potent inhibitor of
      ubiquitin-dependent proteolysis in several cell-free systems. When added to
      reticulocyte lysates or to Xenopus egg extracts, the plant protein effectively
      blocked the degradation of multiubiquitinated lysozyme and cyclin B,
      respectively. MBP1 did not enhance the removal of ubiquitin from lysozyme or
      affect the ability of the 26 S complex to hydrolyze fluorogenic peptides. These
      data suggest that the plant protein specifically interferes with the recognition
      of ubiquitin conjugates by the 26 S protease. Thus MBP1, human S5a, and their
      homologs should prove to be valuable reagents for investigating cellular events
      mediated by ubiquitin-dependent proteolysis.

PMID- 8530352
TI  - A proteasome activator subunit binds calcium.
AB  - We recently cloned a cDNA encoding the 29-kDa subunit of human red blood cell
      regulator (REG), a potent activator of the multicatalytic protease (Realini, C.,
      Dubiel, W., Pratt, G., Ferrell, K., and Rechsteiner, M. (1994) J. Biol. Chem.
      269, 20727-20732). The sequence of this subunit contains 28 "alternating" lysine
      and glutamic acid residues (a KEKE motif). Similar regions are present in a
      number of Ca(2+)-binding proteins, and using standard filter assays, the
      recombinant protein is shown to bind 45Ca2+ and ruthenium red. 45Ca2+ is also
      bound to a ubiquitin extension protein containing the 28-residue KEKE region from
      the 29-kDa REG subunit. Thus, the 29-kDa REG subunit is a Ca(2+)-binding protein,
      and its KEKE region is able to bind divalent cations. Ca2+ reversibly inhibits
      the enhanced peptidase activity of complexes between the multicatalytic protease
      and recombinant REG. This raises the possibility that multicatalytic protease
      activity is regulated by calcium in vivo.

PMID- 8530353
TI  - Spectral tuning in bacteriorhodopsin in the absence of counterion and
      coplanarization effects.
AB  - The basis for wavelength regulation in bacteriorhodopsin (BR) and retinylidene
      proteins in general has been studied for decades but is still only partially
      understood. Here we report the preparation and spectroscopic characterization of
      BR analogs aimed at investigating the existence of spectral tuning mechanisms
      other than the two widely accepted mechanisms, weakened counterion interactions
      and ring/chain coplanarization. We synthesized two novel retinal analogs
      containing a saturated 13-14 bond, which interrupts the interaction of the
      protein counterions with the chromophore conjugation system. Furthermore, one of
      the analogs has a planar polyene system so that the contribution to the red shift
      of BR by retinal ring/chain coplanarization is also absent. We incorporated these
      analogs into bacterioopsin and discovered a sizable amount of red shift, which
      can be accounted for by interactions between the polar or polarizable groups of
      the protein and the retinal polyene chain. Our results suggest that the
      wavelength regulation in BR is achieved by synergistic chromophore/protein
      interactions including ring/chain coplanarization, excited state stabilization by
      polar or polarizable protein side chains located along the polyene chain, and
      weakened counterion interactions near the Schiff base positive charge.

PMID- 8530354
TI  - Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine
      receptors 1 and 2B.
AB  - The CC chemokine monocyte chemoattractant protein-3 (MCP-3) activates human
      monocytes, lymphocytes, basophils, and eosinophils. MCP-3 has been reported to
      induce [Ca2+]i changes in cells transfected with the monocyte-selective MCP-1
      receptor 2B (CC CKR2B) and competes for 125I-MCP-1 binding on CC CKR2B,
      suggesting that it may mediate monocyte responses to MCP-3. However, we now show
      that MCP-3 is a ligand and potent agonist for the macrophage inflammatory protein
      1 alpha (MIP-1 alpha)/regulated on activation, normal T expressed, and secreted
      protein (RANTES) receptor CC CKR1 (rank order for [Ca2+]i changes = MIP-1 alpha >
      MCP-3 > RANTES), which is expressed in monocytes > neutrophils > eosinophils.
      125I-MCP-3 bound directly to CC CKR1 and CC CKR2B (Ki = 8 and 7 nM,
      respectively). Binding to CC CKR1 was competed by all CC chemokines tested except
      MCP-1. In contrast, binding to CC CKR2B was competed only by MCP-3 and MCP-1.
      Both MCP-1 and MCP-3 were equipotent agonists (EC50 = 10 nM for [Ca2+]i changes).
      Thus, MCP-3 is a functional ligand for both CC CKR1 and CC CKR2B, which otherwise
      have distinct selectivities for CC chemokines. These data suggest that monocyte
      responses to MCP-3 could be mediated by both CC CKR2B and CC CKR1, whereas
      eosinophil responses to MCP-3 could be mediated by CC CKR1.

PMID- 8530355
TI  - Efficient plasmid DNA replication in Xenopus egg extracts does not depend on
      prior chromatin assembly.
AB  - Small plasmids replicate efficiently in unfertilized Xenopus eggs provided they
      are injected before rather than after activation of the cell cycle. Here we use
      Xenopus egg extracts to test the hypothesis that efficient replication results
      from chromatin assembly prior to activation giving preloaded plasmids a head
      start toward the formation of a replicating pseudonucleus (Sanchez, J.A., Marek,
      D., and Wangh, L.J. (1992) J. Cell Sci. 103, 907-918). As in ovum, plasmid DNA
      preincubated in unactivated egg cytoplasmcytostatic factor extracts) replicate
      more efficiently after extract activation than does the same DNA added to the
      same extract after activation. Unlike in ovum, however, plasmids that replicate
      efficiently in vitro do not assemble into chromatin during preincubation and
      become topologically knotted instead. But even DNA knotting does not explain
      subsequent efficient replication. Also, plasmids preassembled into chromatin in
      vitro do not replicate efficiently in activated egg cytoplasm unless first
      preincubated in a CSF extract. We conclude that unactivated eggs contain
      replication-enhancing activities that can act independently of plasmid chromatin
      assembly and DNA topology. These postulated "preloading" factor(s) may be related
      to licensing factor, an activity that controls initiation of DNA replication in
      eukaryotic cells. The experimental conditions described here will permit
      characterization of preloading/licensing factor(s) in the context of a small
      plasmid substrate.

PMID- 8530356
TI  - Importance of ribonucleotide availability to proliferating T-lymphocytes from
      healthy humans. Disproportionate expansion of pyrimidine pools and contrasting
      effects of de novo synthesis inhibitors.
AB  - Sensitive high performance liquid chromatography techniques, which differentiate
      between purine and pyrimidine ribonucleoside and deoxyribonucleoside
      triphosphates, were used to quantify pools in phytohemagglutinin-stimulated T
      lymphocytes (98% CD4+ and CD8+) from healthy volunteers. The importance of de
      novo synthesis and salvage was evaluated by incubating the cells with 14C
      radiolabeled precursors (40 microM), azaserine (20 microM; a glutamine
      antagonist), and ribavirin (50 microM; an IMP dehydrogenase inhibitor). We
      confirmed that resting T-lymphocytes meet their metabolic requirements by
      salvage. Noteworthy observations were as follows. First, nucleotide pool
      expansion over 72 h is disproportionate, with that for purines (ATP and GTP)
      being 2-fold compared with up to 8-fold for pyridine (NAD) or pyrimidine (UTP,
      UDP-Glc, and CTP) pools. This supports an additional role for the latter in
      membrane lipid biosynthesis, protein glycosylation, and strand break repair.
      Second, intact de novo pathways are essential for such expansion. Azaserine not
      only inhibited purine synthesis (confirmed by N-formylglycinamide polyphosphate
      accumulation), but also reduced expansion of pyrimidine and NAD pools by 70%.
      Ribavirin depleted GTP pools by 40% and reduced pyrimidine pool expansion by 40%
      at 72 h. These findings underline the importance of pyrimidine ribonucleotide
      availability as well as GTP synthesis de novo to proliferating T-lymphocytes.
      They also demonstrate an absence of coordinate regulation between de novo purine
      and pyrimidine biosynthesis.

PMID- 8530357
TI  - T-lymphocytes from AIDS patients are unable to synthesize ribonucleotides de novo
      in response to mitogenic stimulation. Impaired pyrimidine responses are already
      evident at early stages of HIV-1 infection.
AB  - Proliferative defects have been reported at the level of DNA synthesis, even in T
      lymphocytes from asymptomatic human immunodeficiency virus type-1+ (HIV-1+)
      patients. Since purine and pyrimidine ribonucleotide availability is crucial for
      proliferation, we compared the ability of HIV-1- and HIV-1+ T-lymphocytes (> 95%
      CD4+ and CD8+) to activate de novo biosynthetic and salvage pathways following
      phytohemagglutinin stimulation using 14C-labeled precursors. The striking
      abnormality already detectable in asymptomatic patients' cells was the impaired
      ability of CTP, UDP-Glc, and UTP pools to expand over 72 h (44-70% of control),
      although ATP and GTP pools and responses were normal. In symptomatic patients,
      resting T-cells showed markedly reduced pyrimidine pools (53-74% of control) with
      no change following activation. Relatively normal ATP, GTP, and NAD pools masked
      the same impaired response of de novo synthesis to activation, with ATP and GTP
      being reduced by 50% at 48 h. Purine salvage was more active than the control in
      unstimulated HIV-1+ cells. This impaired de novo synthesis in HIV-1+ T
      lymphocytes severely restricts the availability of ribonucleotides for vital
      growth-related activities such as membrane expansion and strand break repair as
      well as DNA and RNA synthesis. The data indicate that resting T-lymphocytes from
      symptomatic patients survive through enhanced salvage, but the stimulation
      induces metabolic cell death, and provide an explanation for the activation
      associated lymphocyte death seen in HIV-1+ T-lymphocytes.

PMID- 8530358
TI  - Ligand-directed immunoaffinity purification and properties of the one-carbon,
      reduced folate transporter. Interspecies immuno-cross-reactivity and expression
      of the native transporter in murine and human tumor cells and their transport
      altered variants.
AB  - Almost complete purification (> 95%) of the 46-kDa murine, one-carbon, reduced
      folate transporter (RFT) at a recovery of 20% was obtained by ligand-directed
      immunoaffinity fractionation from transporter overproducing L1210/R83 cells.
      These cells were labeled with the N-hydroxysuccinimide ester of [3H]aminopterin
      (AMT), the isolated plasma membrane alkaline washed to remove nonintegral
      membrane proteins, detergent-solubilized, and RFT-separated on an anti-AMT
      antibody-protein G-Sepharose column followed by preparative SDS-polyacrylamide
      gel electrophoresis. Anti-RFT antibody, subsequently derived, differentially
      blotted (L1210/R83 >> L1210/0) a 46-kDa protein during SDS-polyacrylamide gel
      electrophoresis of plasma membrane from L1210/R83 and L1210 cells and in
      L1210/R83 cells after trichloroacetic acid precipitation. In contrast to that
      reported for human tumor cells, glycosidase treatment of RFT revealed no common N
      or O-linked core oligosaccharides associated with this protein. The same 46-kDa
      protein at different relative levels was revealed in a Western blot of plasma
      membrane from other murine tumors. Blotting of plasma membrane from methotrexate
      resistant, transport defective L1210 cell variants exhibited wild-type levels of
      a less electrophoretically mobile RFT or greater levels of the same 46-kDa RFT
      which could not be affinity labeled with N-hydroxysuccinimide-[3H]AMT. The same
      antibody differentially blotted a 83-kDa plasma membrane protein from human HL-60
      and CCRF-CEM cells with different levels of reduced folate transport and affinity
      labeling of RFT, verifying the conserved nature of this protein consistent with
      earlier functional studies.

PMID- 8530359
TI  - The high activity of rat glutathione transferase 8-8 with alkene substrates is
      dependent on a glycine residue in the active site.
AB  - Rat glutathione transferase (GST) 8-8 displays high catalytic activity with
      alpha, beta-unsaturated carbonyl compounds, including lipid peroxidation products
      such as 4-hydroxyalkenals. The catalytic efficiency of the related class Alpha
      GST 1-1 is substantially lower with the same substrates. Chimeric enzymes were
      prepared by replacing N-terminal subunit 8 segments of different lengths (6, 25,
      or 100 residues) with corresponding sequences from subunit 1 using recombinant
      DNA techniques. The chimeric subunit r1(25)r8, containing 25 amino acid residues
      from subunit 1, had the same low activity with alkenal substrates as that
      displayed by subunit 1. Mutation of Ala-12 into Gly in r1(25)r8 gave rise to the
      high alkenal activity characteristic of subunit 8, showing the importance of
      amino acid residue 12 for the activity. However, other structural determinants
      are also essential, as demonstrated by the corresponding Ala-12-->Gly mutation in
      subunit 1, which did not afford high alkenal activity. The results show that a
      single point mutation in a GST subunit may give rise to a 100-fold increase in
      catalytic efficiency with certain substrates. Introduction of such mutations may
      have contributed to the biological evolution of GST isoenzymes with altered
      substrate specificities and may also find use in the engineering of GSTs for
      novel functions.

PMID- 8530360
TI  - Cellular stresses differentially activate c-Jun N-terminal protein kinases and
      extracellular signal-regulated protein kinases in cultured ventricular myocytes.
AB  - Anisomycin or osmotic stress induced by sorbitol activated c-Jun N-terminal
      protein kinases (JNKs) in ventricular myocytes cultured from neonatal rat hearts.
      After 15-30 min, JNK was activated by 10-20-fold. Activation by anisomycin was
      transient, but that by sorbitol was sustained for at least 4 h. In-gel JNK assays
      confirmed activation of two renaturable JNKs of 46 and 55 kDa (JNK-46 and JNK-55,
      respectively). An antibody against human JNK1 immunoprecipitated JNK-46 activity.
      Endothelin-1, an activator of extracellular signal-regulated protein kinases
      (ERKs), also transiently activated JNKs by 2-5-fold after 30 min. Phorbol 12
      myristate 13-acetate did not activate the JNKs although it activated ERK1 and
      ERK2, which phosphorylated the c-Jun transactivation domain in vitro. ATP
      depletion and repletion achieved by incubation in cyanide+deoxyglucose and its
      subsequent removal from the medium activated the ERKs but failed to activate the
      JNKs. Sorbitol (but not anisomycin) also stimulated the ERKs. Sorbitol-stimulated
      JNK activity could be resolved into three peaks by fast protein liquid
      chromatography on a Mono Q column. The two major peaks contained JNK-46 or JNK
      55. These results demonstrate that cellular stresses differentially activate the
      JNKs and ERKs and that there may be "cross-talk" between these MAPK pathways.

PMID- 8530361
TI  - Cloning and expression of murine high molecular mass heat shock proteins, HSP105.
AB  - We have shown that the 105-kDa heat shock protein (HSP105) and the 42 degrees C
      specific heat shock protein (42 degrees C-HSP) constitute high molecular mass
      heat shock proteins. To elucidate the structure of these heat shock proteins, we
      have screened a cDNA library constructed with poly(A)+ RNA derived from mouse
      FM3A cells preheated at 42 degrees C for 2 h using an antibody against murine
      HSP105. Two full-length cDNA clones were obtained: the pB105-1 insert encoded an
      858-amino acid protein, and the pB105-2 insert encoded an 814-amino acid protein
      and lacked 44 amino acids found in pB105-1. The two clones contained the amino
      acid sequence found in the 17-kDa polypeptide fragments from HSP105 and 42
      degrees C-HSP by lysylendopeptidase digestion. In vitro translation products of
      the RNA transcripts from pB105-1 and pB105-2 migrated to the same positions of
      HSP105 and 42 degrees C-HSP, respectively, on SDS-polyacrylamide gel
      electrophoresis. Northern blot analysis showed that the transcript was
      approximately 4 kilobases in murine FM3A cells and was strongly induced by heat
      shock and by treatment with arsenite or an amino acid analog. By reverse
      transcription-polymerase chain reaction analysis using primers by which deletion
      of 132 nucleotides in pB105-2 could be detected, the polymerase chain reaction
      product corresponding to pB105-2 was increased only after heat shock at 42
      degrees C, whereas the product corresponding to pB105-1 was induced by heat shock
      at either 42 or 45 degrees C and also by other stresses. Thus, the cDNA clones
      pB105-1 and pB105-2 encode HSP105 and 42 degrees C-HSP, respectively, and HSP105
      and 42 degrees C-HSP (a short form of HSP105) are suggested to be produced by
      alternative splicing. Here, HSP105 and 42 degrees C-HSP are renamed HSP105 alpha
      and HSP105 beta, respectively. A protein sequence homology search revealed that
      HSP105 shares 54, 34, and 25% amino acid identity with human HSP70RY, the sea
      urchin egg receptor for sperm, and murine inducible HSP70, respectively.
      Furthermore, by Northern blot analysis, HSP105 mRNA was revealed to be present in
      most murine tissues and to be highly expressed in the brain.

PMID- 8530362
TI  - A novel, phospholipase C-independent pathway of inositol 1,4,5-trisphosphate
      formation in Dictyostelium and rat liver.
AB  - In an earlier study a mutant Dictyostelium cell-line (plc-) was constructed in
      which all phospholipase C activity was disrupted and nonfunctional, yet these
      cells had nearly normal Ins(1,4,5)P3 levels (Drayer, A.L., Van Der Kaay, J.,
      Mayr, G.W, Van Haastert, P.J.M. (1990) EMBO J. 13, 1601-1609). We have now
      investigated if these cells have a phospholipase C-independent de novo pathway of
      Ins(1,4,5)P3 synthesis. We found that homogenates of plc- cells produce
      Ins(1,4,5)P3 from endogenous precursors. The enzyme activities that performed
      these reactions were located in the particulate cell fraction, whereas the
      endogenous substrate was soluble and could be degraded by phytase. We tested
      various potential inositol polyphosphate precursors and found that the most
      efficient were Ins(1,3,4,5,6)P5, Ins(1,3,4,5)P4, and Ins(1,4,5,6)P4. The
      utilization of Ins(1,3,4,5,6)P5, which can be formed independently of
      phospholipase C by direct phosphorylation of inositol (Stephens, L.R. and Irvine,
      R.F. (1990) Nature 346, 580-582), provides Dictyostelium with an alternative and
      novel pathway of de novo Ins(1,4,5)P3 synthesis. We further discovered that
      Ins(1,3,4,5,6)P5 was converted to Ins(1,4,5)P3 via both Ins(1,3,4,5)P4 and
      Ins(1,4,5,6)P4. In the absence of calcium no Ins(1,4,5)P3 formation could be
      observed; half-maximal activity was observed at low micromolar calcium
      concentrations. These reaction steps could also be performed by a single enzyme
      purified from rat liver, namely, the multiple inositol polyphosphate phosphatase.
      These data indicate that organisms as diverse as rat and Dictyostelium possess
      enzyme activities capable of synthesizing the second messengers Ins(1,4,5)P3 and
      Ins(1,3,4,5)P4 via a novel phospholipase C-independent pathway.

PMID- 8530363
TI  - Adenylylcyclase supersensitization in mu-opioid receptor-transfected Chinese
      hamster ovary cells following chronic opioid treatment.
AB  - Using CHO cells stably transfected with rat mu-opioid receptor cDNA, we show that
      the mu-agonists morphine and [D-Ala2,N-methyl-Phe4,Gly-ol5]enkephalin are
      negatively coupled to adenylylcyclase and inhibit forskolin-stimulated cAMP
      accumulation. Chronic exposure of cells to morphine leads to the rapid
      development of tolerance. Withdrawal of morphine or [D-Ala2,N-methyl-Phe4,Gly
      ol5]enkephalin following chronic treatment (by wash or addition of the antagonist
      naloxone) leads to an immediate increase in cyclase activity (supersensitization
      or overshoot), which is gradually reversed upon further incubation with naloxone.
      Phosphodiesterase inhibitors do not affect the overshoot, indicating that it
      results from cyclase stimulation rather than phosphodiesterase regulation.
      Morphine's potency to inhibit cAMP accumulation is the same before and after
      chronic treatment, suggesting that the apparent tolerance results from cyclase
      activation, rather than from receptor desensitization. The similar kinetics of
      induction of tolerance and overshoot support this idea. Both the overshoot and
      acute opioid-induced cyclase inhibition are blocked by naloxone and are pertussis
      toxin-sensitive, indicating that both phenomena are mediated by the mu-receptor
      and Gi/G(o) proteins. The supersensitization is cycloheximide-insensitive,
      indicating that it does not require newly synthesized proteins. This is supported
      by the rapid development of supersensitization. Taken together, these results
      show that mu-transfected cells can serve as a model for investigating molecular
      and cellular mechanisms underlying opiate drug addiction.

PMID- 8530364
TI  - A novel cytochrome P450 expressed primarily in brain.
AB  - hct-1 (hippocampal transcript) was detected in a differential screen of a rat
      hippocampal cDNA library. Expression of hct-1 was enriched in the formation but
      was also detected in rat liver and kidney, though at much lower levels;
      expression was barely detectable in testis, ovary, and adrenal. In liver, unlike
      brain, expression was sexually dimorphic; hepatic expression was greatly reduced
      in female rats. In mouse, brain expression was widespread, with the highest
      levels being detected in corpus callosum; only low levels were detected in liver.
      Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with
      cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that
      metabolize a range of substrates including steroids, fatty acids, and
      xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid
      sequence) to cholesterol 7 alpha-hydroxylase (CYP7) and contains a postulated
      steroidogenic domain present in other steroid-metabolizing CYPs but clearly
      represents a type of CYP not previously reported. Genomic Southern analysis
      suggests that a single gene corresponding to hct-1 is present in mouse, rat, and
      human. hct-1 is unusual in that, unlike all other CYPs described, the primary
      site of expression is in the brain. Similarity to CYP7 and other steroid
      metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism
      in brain, notable because of the documented ability of brain-derived steroids
      (neurosteroids) to modulate cognitive function in vivo.

PMID- 8530365
TI  - Protein conformational changes during the bacteriorhodopsin photocycle. A Fourier
      transform infrared/resonance Raman study of the alkaline form of the mutant Asp
      85-->Asn.
AB  - Bacteriorhodopsin is a light-driven proton pump, which undergoes a photocycle
      consisting of several distinct intermediates. Previous studies have established
      that the M-->N step of this photocycle involves a major conformational change of
      membrane embedded alpha-helices. In order to further investigate this
      conformational change, we have studied the photocycle of the high pH form of the
      mutant Asp-85-->Asn (D85Nalk). In contrast to wild type bacteriorhodopsin,
      D85Nalk has a deprotonated Schiff base and a blue-shifted absorption near 410 nm,
      yet it still transports protons in the same direction as wild type
      bacteriorhodopsin (Tittor, J., Schweiger, U., Oesterhelt, D. and Bamberg, E.
      (1994) Biophys. J., 67, 1682-1690). Resonance Raman spectroscopy of D85Nalk and
      D85Nalk regenerated with retinal labeled at the C-15 position with deuterium
      reveals the existence of an all-trans configuration of the chromophore. Fourier
      transform infrared difference spectroscopy shows that the photocycle of this
      light-adapted form involves similar events as the wild type bacteriorhodopsin
      photocycle including the M-->N protein conformational change. These results help
      to explain the ability of D85Nalk to transport protons and demonstrate that the M
      ->N conformational change can occur even in the photocycle of an unprotonated
      Schiff base form of bacteriorhodopsin.

PMID- 8530366
TI  - Selective interactions of UPIa and UPIb, two members of the transmembrane 4
      superfamily, with distinct single transmembrane-domained proteins in
      differentiated urothelial cells.
AB  - The transmembrane 4 (TM4) superfamily contains many important leukocyte
      differentiation-related surface proteins including CD9, CD37, CD53, and CD81;
      tumor-associated antigens including CD63/ME491, CO-029, and SAS; and a newly
      identified metastasis suppressor gene R2. Relatively little is known, however,
      about the structure and aggregation state of these four transmembrane-domained
      proteins. The asymmetrical unit membrane (AUM), believed to play a major role in
      stabilizing the apical surface of mammalian urothelium thus preventing it from
      rupturing during bladder distention, contains two TM4 members, the uroplakins
      (UPs) Ia and Ib. In association with two other (single transmembrane-domained)
      membrane proteins, UPII and UPIII, UPIa and UPIb form 16-nm particles that
      naturally form two-dimensional crystalline arrays, thus providing unique
      opportunities for studying membrane structure and function. To better understand
      how these proteins interact to form the 16-nm particles, we analyzed their
      nearest neighbor relationship by chemical cross-linking. We show here that UPIa
      and UPIb, which share 39% of their amino acid sequence, are cross-linked to UPII
      and UPIII, respectively. We also show that UPIa has a propensity to oligomerize,
      forming complexes that are stable in SDS, and that UPII can be readily cross
      linked to form homodimers. The formation of UPII homodimers is sensitive,
      however, to octyl glucoside that can solubilize the AUMs. These data suggest that
      there exist two types of 16-nm AUM particles that contain UPIa/UPII or
      UPIb/UPIII, and support a model in which the UPIa and UPII occupy the inner and
      outer domains, respectively, of the UPIa/UPII particle. This model can account
      for the apparent "redundancy" of the uroplakins, as the structurally related UPIa
      and UPIb, by interacting with different partners, may play different roles in AUM
      formation. The model also suggests that AUM plaques with different uroplakin
      compositions may differ in their assembly, and in their abilities to interact
      with an underlying cytoskeleton. Our data indicate that two closely related TM4
      proteins, UPIa and UPIb, can be present in the same cell, interacting with
      distinct partners. AUM thus provides an excellent model system for studying the
      targeting, processing, and assembly of TM4 proteins.

PMID- 8530367
TI  - Lysolecithin-induced alteration of subendothelial heparan sulfate proteoglycans
      increases monocyte binding to matrix.
AB  - The cause and consequence of altered proteoglycans in atherosclerosis are poorly
      understood. To determine whether proteoglycans affect monocyte binding, we
      studied the effects of heparin and proteoglycan degrading enzymes on THP-1
      monocyte adhesion to subendothelial matrix (SEM). Monocyte binding increased
      about 2-fold after SEM was treated with heparinase. In addition, heparin
      decreased monocyte binding to fibronectin, a known SEM protein, by 60%. These
      data suggest that SEM heparan sulfate inhibits monocyte binding to SEM proteins.
      We next examined whether lysolecithin, a constituent of modified lipoproteins,
      affects endothelial heparan sulfate proteoglycan (HSPG) production and monocyte
      binding. Lysolecithin (10-200 microM) decreased total 35SO4 in SEM (20-75%). 2
      fold more monocytes bound to SEM from lysolecithin treated cells than to control
      SEM. Heparinase treatment did not further increase monocyte binding to
      lysolecithin-treated SEM. HSPG degrading activity was found in medium from
      lysolecithin-treated but not control cells. 35SO4-labeled products obtained from
      labeled matrix treated with lysolecithin-conditioned medium were similar in size
      to those generated by heparinase. These data suggest that lysolecithin-treated
      endothelial cells secrete a heparanase-like activity. We hypothesize that
      decreased vessel wall HSPG, as occurs in atherogenic conditions, allows increased
      monocyte retention within the vessel and is due to the actions of an endothelial
      heparanase.

PMID- 8530368
TI  - A novel cytochrome b5-like domain is linked to the carboxyl terminus of the
      Saccharomyces cerevisiae delta-9 fatty acid desaturase.
AB  - Cytochrome b5 is an amphipathic mobile membrane protein that is predominantly
      located at the endoplasmic reticulum surface. It is an essential component of a
      number of membrane-bound redox systems. In animal and fungal cells cytochrome b5
      is thought to be an electron donor for sterol modifying enzymes and fatty acid
      desaturases. Disruption of the Saccharomyces cytochrome b5 gene, however, yielded
      cells that had no nutritional requirement for either sterols or unsaturated fatty
      acids. Expression of sterol and fatty acid-modifying genes was increased in the
      cytochrome b5-disrupted cells, however, suggesting that cytochrome b5 may play
      some nonessential role in these functions. Unsaturated fatty acids in yeast are
      formed by Ole1p, an oxygen-dependent delta-9 fatty acid desaturase that is an
      intrinsic endoplasmic reticulum membrane protein. Although the yeast delta-9
      fatty acid desaturase does not appear to require cytochrome b5, introduction of
      the rat liver stearoyl-CoA desaturase gene into an ole1-disrupted, cytochrome b5
      disrupted yeast strain revealed that this enzyme specifically requires cytochrome
      b5 to function. Comparison of the coding sequences of the yeast and rat
      desaturase genes showed that the yeast protein contains a 113-amino acid carboxyl
      terminal extension not found in the rat enzyme. That extension has regions of
      strong homology to cytochrome b5, particularly in the heme binding and electron
      transfer motifs. Truncation or disruption of the desaturase cytochrome b5-like
      domain in cells that contain the wild type diffusible b5 produced unsaturated
      fatty acid auxotrophy, suggesting that the cytochrome b5-like domain of Ole1p
      plays an essential role in the desaturase reaction.

PMID- 8530369
TI  - Autophosphorylation induces autoactivation and a decrease in the Src homology 2
      domain accessibility of the Lyn protein kinase.
AB  - Lyn is a member of the Src family of protein-tyrosine kinases that can readily
      undergo autophosphorylation in vitro. The site of autophosphorylation is Tyr397
      which corresponds to the consensus autophosphorylation site of other Src family
      tyrosine kinases. The rate of autophosphorylation is concentration-dependent,
      indicating that the reaction follows an intermolecular mechanism.
      Autophosphorylation results in a 17-fold increase in protein-tyrosine kinase
      activity. Kinetic analysis demonstrates that phosphorylation of a substrate
      peptide by Lyn following autophosphorylation occurs with a 63-fold decrease in Km
      but no significant change in Vmax, suggesting that autophosphorylation relieves
      the conformational constraint that prevents binding of the substrate peptide to
      the active site of the kinase. Using a phosphotyrosine-containing peptide (pYEEI)
      that has previously been shown to bind to the Src homology 2 (SH2) domain of Src
      family tyrosine kinases with high affinity, we found that autophosphorylation
      results in a significant decrease in accessibility of the Lyn SH2 domain,
      indicating that conformational changes in the protein kinase domain induced by
      autophosphorylation can be propagated to the SH2 domain. Our study suggests that
      autophosphorylation plays an important role in regulating Lyn by modulating both
      its kinase activity and its interaction with other phosphotyrosine-containing
      molecules.

PMID- 8530370
TI  - Functional association between the human myeloid immunoglobulin A Fc receptor
      (CD89) and FcR gamma chain. Molecular basis for CD89/FcR gamma chain association.
AB  - FcR gamma chain has previously been shown to interact with the TCR-CD3 complex,
      the IgE Fc receptor I (Fc epsilon RI), and the class I and IIIA IgG receptors (Fc
      gamma RI and Fc gamma RIIIa). Here, we demonstrate that the Fc receptor gamma
      chain associates with Fc alpha R in transfected IIA1.6 B lymphocytes. Fc alpha R
      could be expressed at the surface of IIA1.6 B cells by itself, but was devoid of
      signaling capacity. Upon co-expression of FcR gamma chain, a physical interaction
      with Fc alpha R could be demonstrated. This association proved crucial for the
      triggering of both proximal (intracellular calcium increase and tyrosine
      phosphorylation), as well as distal (IL-2 release), signal transduction
      responses. We next tested the hypothesis that a positively charged arginine
      residue (Arg209) within the transmembrane domain of Fc alpha R promotes
      association with FcR gamma chain. We therefore constructed Fc alpha R molecules
      where Arg209 was mutated to either a positively charged histidine, a negatively
      charged aspartic acid, or an uncharged leucine. A functional association between
      Fc alpha R and FcR gamma chain was observed only with a positively charged
      residue (Arg209 or His209) present within the Fc alpha R transmembrane domain.
      These data show that transmembrane signal transduction by the Fc alpha R is
      mediated via FcR gamma chain, and that Fc alpha R requires a positively charged
      residue within the transmembrane domain to promote functional association.

PMID- 8530371
TI  - Novel aromatic isothiouronium derivatives which act as high affinity competitive
      antagonists of alkali metal cations on Na/K-ATPase.
AB  - This paper describes properties of a novel family of aromatic isothiouronium
      derivatives, which act as Na(+)-like competitive antagonists on renal Na/K
      ATPase. The derivatives are reversible competitors of Rb+ and Na+ occlusion. Ki
      values of the most potent compounds, 1-bromo-2,4,6
      tris(methylisothiouronium)benzene (Br-TITU) and 1,3-dibromo-2,4,6
      tris(methylisothiouronium)benzene(Br2-TITU ), 0.65 and 0.32 microM, respectively,
      are 15-30-fold lower than Ki values of the bis-guanidinium derivatives described
      previously (David, P., Mayan, H., Cohen, H., Tal, D. M., and Karlish, S. J. D.
      (1992) J. Biol. Chem. 267, 1141-1149), and represent the lowest reported values
      for cation antagonists. Using fluorescein-labeled Na/K-ATPase, all derivatives
      have been shown to stabilize the E1 conformation when bound at high affinity
      sites (i.e. they are sodium-like). In addition, in one condition (10 mM Tris-HCl,
      pH 8.1), high concentrations of Br-TITU (KD approximately 10 microM) appear to
      stabilize an E2 conformation. We propose a model which allows for simultaneous
      binding of the antagonists to high affinity cytoplasmic sites and low affinity
      sites, which may be at the extracellular surface. Blockage of cation occlusion by
      the isothiouronium derivatives at the cytoplasmic surface probably occurs at the
      entrance to the occlusion sites, which is recognized both by Na+ antagonists and
      by Na+ or K+ ions. Unlike the alkali metal cations, the Na+ antagonists are not
      occluded or transported (see also Or, E., David, P., Shainskaya, A., Tal, D. M.,
      and Karlish, S. J. D. (1993) J. Biol. Chem. 268, 16929-16937). The isothiouronium
      derivatives appear to be promising candidates for further development as affinity
      labels of cation binding domains, for kinetic analysis of isoforms or mutated
      Na/K pumps, or as probes of other cation transport proteins.

PMID- 8530372
TI  - Organization of the gene encoding the human endothelin-converting enzyme (ECE-1).
AB  - The two human endothelin-converting enzyme (ECE-1) isoforms, which differ by
      their N-terminal region, are encoded by a single gene. The gene is composed of 19
      exons that span more than 68 kilobases and has been mapped to the 1p36 band of
      the human genome. The two isoform mRNAs display different tissue distributions.
      Their precursors are transcribed from two distinct start sites, upstream from
      exon 1 and exon 3, respectively. Sequence analysis of the two putative promoters
      revealed the presence of motifs characteristic for several transcription factors.
      Comparison of the ECE-1 gene structure with those of other zinc metalloproteases,
      as well as a phylogenetic study, confirm the existence of a metalloprotease
      subfamily composed of ECE-1, ECE-2, neutral endopeptidase, Kell blood group
      protein, and two bacterial enzymes.

PMID- 8530373
TI  - Purification and characterization of protease Ci, a cytoplasmic
      metalloendoprotease in Escherichia coli.
AB  - Protease Ci, a cytoplasmic metalloprotease in Escherichia coli, has been purified
      to apparent homogeneity by conventional chromatographic procedures using 125I
      labeled oxidized insulin B-chain as a substrate. The purified enzyme behaves as a
      54-kDa protein under both denaturing and nondenaturing conditions, suggesting
      that it consists of a single polypeptide chain. It is inhibited by metal
      chelating agents, including o-phenanthroline and NaCN, but not by inhibitors of
      serine proteases or thiol-blocking agents. Furthermore, protease Ci was found to
      contain 1.1 mol of zinc per mol of the enzyme upon analysis by HR ICP mass
      spectroscopy. Thus, protease Ci must be a zinc metalloprotease. Among the
      polypeptides tested as substrates, oxidized insulin B-chain and glucagon are most
      rapidly hydrolyzed. Intact insulin is a much poorer substrate than oxidized
      insulin B-chain, even though the affinity of the enzyme to intact insulin is
      approximately 100-fold greater than that to the B-chain. Since unlabeled oxidized
      insulin A-chain is capable of inhibiting the hydrolysis of 125I-labeled insulin B
      chain, it also appears to be a substrate. Protease Ci also degrades lysozyme and
      lactalbumin, although to a much lesser extent than oxidized insulin B-chain.
      However, it shows little or no activity against proteins larger than 15 kDa (e.g.
      ovalbumin and denatured bovine serum albumin). Hydrolysis of oxidized insulin B
      chain followed by amino acid composition analyses of the cleavage products
      reveals that as many as 10 of its 29 peptide bonds are hydrolyzed by protease Ci.
      This ability to hydrolyze relatively small polypeptides suggests that protease Ci
      may catalyze the later steps in the pathway for intracellular protein breakdown.

PMID- 8530374
TI  - Structural and functional characteristics of partially disulfide-reduced
      intermediates of ovotransferrin N lobe. Cystine localization by indirect end
      labeling approach and implications for the reduction pathway.
AB  - Ovotransferrin N lobe contains six intrachain disulfides (SS-I/Cys10-Cys45; SS
      II/Cys20-Cys36; SS-III/Cys115-Cys197; SS-IV/Cys160-Cys174; SS-V/Cys171-Cys182; SS
      VI/Cys228-Cys242) in a single polypeptide chain of 332 amino acid residues. Upon
      the protein disulfide reduction with dithiothreitol under nondenaturing
      conditions, the intermediate species with four, three, and two disulfides were
      generated. The partially disulfide-reduced intermediates were isolated, and the
      localization of intact disulfides in the intermediates was determined by an
      indirect end-labeling method. This method included the S-cyanocysteine-specific
      protein fragmentation, followed by gel electrophoresis and the immunochemical
      visualization of the C terminus-intact fragments using antiserum raised against a
      non-cysteine C-terminal fragment (Ser280-Arg332). Results clearly showed that
      first SS-IV and SS-V, second SS-III, and then SS-VI are cleaved. No reduction was
      observed for SS-I and SS-II under the employed reducing conditions. The
      conclusion was confirmed by peptide mapping analyses for the same disulfide
      intermediates using reverse phase high performance liquid chromatography.
      Transverse urea gradient gel electrophoresis and visible absorption spectra
      revealed that the four-disulfide intermediate, but not the three- or two
      disulfide intermediate, retains essentially the same iron-binding function as the
      native protein. By far-UV CD analyses, the residual native conformation of the
      partially disulfide-reduced intermediates was found to decrease with increased
      number of the reduced disulfides. Implications of the partially disulfide-reduced
      intermediates for the disulfide-reductive unfolding pathway in ovotransferrin N
      lobe are discussed.

PMID- 8530375
TI  - Chimeric molecules between keratinocyte growth factor and basic fibroblast growth
      factor define domains that confer receptor binding specificities.
AB  - Basic fibroblast growth factor (FGF) and keratinocyte growth factor (KGF) are
      structurally related fibroblast growth factors, yet they exhibit distinct
      receptor binding specificity. Basic FGF binds with high affinity to FGFR1, FGFR2,
      and FGFR4, whereas KGF does not interact with these receptors and can only bind
      an isoform of FGFR2 known as the KGFR. Basic GFG binds KGFR but with lower
      affinity than KGF. In order to identify domains that confer this specificity,
      four reciprocal chimeras were generated between the two growth factors and were
      analyzed for receptor recognition and biological activity. The chimeras are
      designated BK1 (bFGF1-54:KGF91-194), BK2 (bFGF1-74:KGF111-194), KB1 (KGF31
      90:bFGF55-155), and KB2 (KGF31-110:bFGF75-155). The two BK chimera similarly
      interacted with FGFR1 and FGFR4 but differed from each other with respect to KGFR
      recognition. BK1 displayed a slightly better affinity for KGFR than BK2 and
      induced a higher level of DNA synthesis in keratinocytes compared with bFGF and
      BK2. A neutralizing monoclonal antibody directed against bFGF specifically
      neutralized the biological activity of the BK chimeras. The reciprocal chimeras,
      KB1 and KB2, exhibited KGF-like receptor binding and activation properties.
      However, KB2 displayed higher affinity for KGFR and was significantly more potent
      mitogen that KB1. Altogether, our results suggest that the amino-terminal part of
      KGF and bFGF plays an important role in determining their receptor binding
      specificity. In addition, the results point to the contribution of a segment from
      the middle part of KGF (residues 91-110) for recognition and activation of the
      KGFR, as the two chimeras containing these residues (BK1 and KB2) displayed an
      enhanced interaction with the KGFR.

PMID- 8530377
TI  - Substrate specificities of the insulin and insulin-like growth factor 1 receptor
      tyrosine kinase catalytic domains.
AB  - To compare the substrate specificities of the insulin and insulin-like growth
      factor 1 (IGF-1) receptor tyrosine kinases, the catalytic domains of the enzymes
      have been expressed in Escherichia coli as fusion proteins. The purified proteins
      have kinase activity, demonstrating that the catalytic domain of IGF-1 receptor,
      like that of insulin receptor, is active independent of its ligand-binding and
      transmembrane domains. The specificities of the two enzymes for the divalent
      cations Mg2+ and Mn2+ are indistinguishable. A series of peptides has been
      prepared that reproduces the major phosphorylation sites of insulin receptor
      substrate-1, a common substrate for the two receptor tyrosine kinases in vivo.
      Insulin and IGF-1 receptors show distinct preferences for these peptides; whereas
      insulin receptor prefers peptides based on Tyr-987 or Tyr-727 of insulin receptor
      substrate-1, the IGF-1 receptor preferentially recognizes the Tyr-895 site. The
      latter site, when phosphorylated, is a binding site for the SH2 domain-containing
      adapter protein Grb2. The ability of the two receptor tyrosine kinases to be
      phosphorylated and activated by v-Src has also been examined. The catalytic
      activity of IGF-1 receptor is stimulated approximately 3.4-fold by treatment with
      purified v-Src, while insulin receptor shows very little effect of Src
      phosphorylation under these conditions. This observation is relevant to recent
      findings of IGF-1 receptor activation in Src-transformed cells, and may represent
      one method by which Src amplifies its mitogenic signal. Collectively the data
      suggest that the catalytic domains of the two receptor kinases possess inherently
      different substrate specificities and signaling potentials.

PMID- 8530376
TI  - Differential glycosylation and intracellular trafficking for the long and short
      isoforms of the D2 dopamine receptor.
AB  - The D2 dopamine receptor exists in two alternatively spliced isoforms, "long" and
      "short" (D2L and D2S), which differ by 29 amino acids in the third cytoplasmic
      domain. The functional differences between these two isoforms are still obscure.
      We have performed pulse-chase studies on the D2L and D2S receptors expressed in
      CHO cells in order to follow the post-translational processing of the two
      isoforms. Both isoforms are present in three post-translational states: a newly
      synthesized protein, a partially glycosylated product, and a fully glycosylated
      mature 70-kDa receptor. However, the processing to the mature receptor differs
      between the two isoforms. First, the D2S receptor is processed to the mature 70
      kDa species faster than the D2L receptor. Second, at 20 degrees C the D2S isoform
      is fully processed to the 70-kDa species, whereas the D2L isoform persists in its
      partially processed 45-kDa state. Finally, a significant portion of the D2L
      receptor remains in its partially processed form in an intracellular compartment
      and does not reach the plasma membrane. These results give rise to the suggestion
      that the difference observed between the two alternatively spliced isoforms of
      the D2 receptor may lie in their post-translational processing and intracellular
      trafficking.

PMID- 8530378
TI  - SecA-independent translocation of the periplasmic N-terminal tail of an
      Escherichia coli inner membrane protein. Position-specific effects on
      translocation of positively charged residues and construction of a protein with a
      C-terminal translocation signal.
AB  - We have shown previously that the 100-residue-long periplasmic N-terminal tail of
      the Escherichia coli inner membrane protein ProW can be translocated across the
      inner membrane in a sec-independent manner and that its translocation is blocked
      by the introduction of three positively charged residues near its C-terminal end
      (Whitley, P., Zander, T., Ehrmann, M., Haardt, M., Bremer, E., and von Heijne, G.
      (1994) EMBO J. 13, 4653-4661). We have now further analyzed the requirements for
      translocation of the N-terminal tail and found that the introduction of even a
      single arginine can block translocation. Position-specific differences in the
      effects on translocation of arginine insertions suggest that the C-terminal end
      of the N-terminal tail is more critical for translocation than the central and N
      terminal regions. We also show that the N-terminal tail is translocated in a
      truncation mutant where a stop codon is placed immediately after the first
      transmembrane segment, provided that the transmembrane segment is flanked on its
      C-terminal end by positively charged residues. Thus, sec-independent
      translocation of a relatively large domain can be induced by a translocation
      signal located at the extreme C terminus of a protein.

PMID- 8530379
TI  - Synthesis and intracellular transport of aminoglycerophospholipids in
      permeabilized cells of the yeast, Saccharomyces cerevisiae.
AB  - The sequence of biosynthetic steps from phosphatidylserine to
      phosphatidylethanolamine (via decarboxylation) and then phosphatidylcholine (via
      methylation) is linked to the intracellular transport of these
      aminoglycerophospholipids. Using a [3H]serine precursor and permeabilized yeast
      cells, it is possible to follow the synthesis of each of the
      aminoglycerophospholipids and examine the requirements for their interorganelle
      transport. This experimental approach reveals that in permeabilized cells newly
      synthesized phosphatidyl-serine is readily translocated to the locus of
      phosphatidylserine decarboxylase 1 in the mitochondria but not to the locus of
      phosphatidylserine decarboxylase 2 in the Golgi and vacuoles. Phosphatidylserine
      transport to the mitochondria is ATP independent and exhibits no requirements for
      cytosolic factors. The phosphatidylethanolamine formed in the mitochondria is
      exported to the locus of the methyltransferases (principally the endoplasmic
      reticulum) and converted to phosphatidylcholine. The export of
      phosphatidylethanolamine requires ATP but not any other cytosolic factors and is
      not obligately coupled to methyltransferase activity. The above described lipid
      transport reactions also occur in permeabilized cells that have been disrupted by
      homogenization, indicating that the processes are extremely efficient and may be
      dependent upon stable structural elements between organelles.

PMID- 8530380
TI  - Nuclear phospholipase D in Madin-Darby canine kidney cells. Guanosine 5'-O
      (thiotriphosphate)-stimulated activation is mediated by RhoA and is downstream of
      protein kinase C.
AB  - We have recently demonstrated the existence of an ATP-activated phospholipase D
      (PLD) in the nuclei of MDCK-D1 cells (Balboa, M. A., Balsinde, J., Dennis, E. A.,
      and Insel, P. A. (1995) J. Biol. Chem. 270, 11738-11740). We have now found that
      nuclear PLD is synergistically activated by guanosine 5'-O-(thiotriphosphate)
      (GTP gamma S) and ATP in a time- and concentration-dependent manner, but these
      compounds do not alter the sensitivity of the enzyme to activation by Ca2+. The
      synergistic stimulation of PLD activity could be blocked by addition of the
      protein kinase C inhibitors chelerythrine and calphostin C. Stimulation by GTP
      gamma S was abolished by guanosine 5'-O-(2-thiodiphosphate). Incubation of
      isolated nuclei with Clostridium botulinum C3 exoenzyme inhibited the
      potentiating effect of GTP gamma S on ATP-dependent nuclear PLD activity.
      Moreover, use of the Rho GDP dissociation inhibitor to extract Rho family G
      proteins from cell nuclei also inhibits PLD activity. Western blot analyses of
      isolated nuclei revealed the presence of the small G protein RhoA, but not of
      RhoB or the ADP-ribosylation factor. GTP gamma S-stimulated ATP-dependent PLD
      activity could be reconstituted in Rho GDP dissociation inhibitor-washed nuclei
      by addition of recombinant prenylated RhoA, but not by addition of non-prenylated
      RhoA. Taken together, these results indicate that nuclear PLD activity is
      modulated via a RhoA-dependent activation that occurs downstream of protein
      kinase C. Nuclear PLD, which appears to be a previously unrecognized effector
      regulated by protein kinase C and G proteins, may be involved in the regulation
      of nuclear function or structure.

PMID- 8530381
TI  - The mitochondrial protein import machinery. Role of ATP in dissociation of the
      Hsp70.Mim44 complex.
AB  - Interaction of preproteins with the heat shock protein Hsp70 in the mitochondrial
      matrix is required for driving protein transport across the mitochondrial inner
      membrane. Binding of mt-Hsp70 to the protein Mim44 of the inner membrane import
      site seems to be an essential part of an ATP-dependent reaction cycle. However,
      the available results on the role played by ATP are controversial. Here we
      demonstrate that the mt-Hsp70.Mim44 complex contains ADP and that a
      nonhydrolyzable analog of ATP dissociates the mt-Hsp70.Mim44 complex in the
      presence of potassium ions. The previously reported requirement of ATP hydrolysis
      for complex dissociation was due to the use of a nonphysiological concentration
      of sodium ions. In the presence of potassium ions, mt-Hsp70 undergoes a
      conformational change that is not observed with a mutant Hsp70 defective in
      binding to Mim44. The mutant Hsp70 is able to bind substrate proteins,
      differentiating binding to Mim44 from binding to substrate proteins. We conclude
      that binding of ATP, not hydrolysis, is required to dissociate the mt-Hsp70.Mim44
      complex and that the reaction cycle includes an ATP-induced conformational change
      of mt-Hsp70.

PMID- 8530382
TI  - Molecular cloning, expression, and partial characterization of two novel members
      of the ovalbumin family of serine proteinase inhibitors.
AB  - A human placental lambda gt11 cDNA library was screened for sequences encoding
      proteins related to human proteinase inhibitor 6 (PI6), and two plaques were
      identified that displayed weak hybridization at high stringency. Isolation and
      characterization of the DNA inserts revealed two novel sequences encoding
      proteins composed of 376 and 374 amino acids with predicted molecular masses of
      approximately 42 kDa. The novel proteins displayed all of the structural features
      unique to the ovalbumin family of intracellular serpins including the apparent
      absence of a cleavable N-terminal signal sequence. The degree of amino acid
      sequence identity between the novel serpins and PI6 (63-68%) significantly
      exceeds that of any other combination of known intracellular serpins. The two
      novel serpins encoded by the two novel cDNA sequences have been designated as
      proteinase inhibitor 8 (PI8) and proteinase inhibitor 9 (PI9). The putative
      reactive center P1-P1' residues for PI8 and PI9 were identified as Arg339-Cys340
      and Glu340-Cys341, respectively. PI9 appears to be unique in that it is the first
      human serpin identified with an acidic residue in the reactive center P1
      position. In addition, the reactive center loop of PI9 exhibits 54% identity with
      residues found in the reactive center loop of the cowpox virus CrmA serpin. Two
      PI8 transcripts of 1.4 kilobases (kb) and 3.8 kb were detected by Northern
      analysis in equal and greatest abundance in liver and lung, while the 1.4-kb mRNA
      was in excess over the 3.8-kb mRNA in skeletal muscle and heart. Two PI9
      transcripts of 3.4 and 4.4 kb were detected in equal and greatest abundance in
      lung and placenta and were weakly detected in all other tissues. PI8 and PI9 were
      expressed in baby hamster kidney and yeast cells, respectively. Immunoblot
      analyses using rabbit anti-PI6 IgG indicated the presence of PI8 in the cytosolic
      fraction of stably transfected cells that formed an SDS-stable 67-kDa complex
      with human thrombin. PI9 was purified to homogeneity from the yeast cell lysate
      by a combination of heparin-agarose chromatography and Mono Q fast protein liquid
      chromatography and migrated as a single band in SDS-polyacrylamide gel
      electrophoresis with an apparent molecular mass of 42 kDa. Purified recombinant
      PI9 failed to inhibit the amidolytic activities of trypsin, papain, thrombin, or
      Staphylococcus aureus endoproteinase Glu-C and did not form an SDS-stable complex
      when incubated with thrombin. The cognate intracellular proteinases that interact
      with PI8 and PI9 are unknown.

PMID- 8530383
TI  - Functional characterization of the human interleukin-15 receptor alpha chain and
      close linkage of IL15RA and IL2RA genes.
AB  - Interleukins-2 and -15 (IL-2 and IL-15) are cytokines with overlapping but
      distinct biological effects. Their receptors share two subunits (the IL-2R beta
      and -gamma chains) that are essential for signal transduction. The IL-2 receptor
      requires an additional IL-2-specific alpha subunit for high affinity IL-2
      binding. Recently, a murine IL-15-specific alpha subunit was identified, cloned,
      and shown to be structurally related to IL-2R alpha. However, the murine IL-15R
      alpha alone bound IL-15 with a 1000-fold higher affinity than that seen with IL
      2R alpha and IL-2. We now extend these studies into the human system with the
      isolation of three differentially spliced human IL-15R alpha variants that are
      all capable of high affinity binding of IL-15. The cytoplasmic domain of IL-15R
      alpha, like that of IL-2R alpha, is dispensable for mitogenic signaling,
      suggesting that the primary role of the alpha chains is to confer high affinity
      binding. At high concentrations, IL-15, like IL-2, is able to signal through a
      complex of IL-2R beta and -gamma in the absence of the alpha subunit.
      Furthermore, the IL15RA and IL2RA genes have a similar intron-exon organization
      and are closely linked in both human and murine genomes. However, the
      distribution of expression of the IL-15R alpha is much wider than that of the IL
      2R alpha, suggesting a broader range of cellular targets for IL-15.

PMID- 8530384
TI  - Functional characterization of the murine homolog of the B cell-specific
      coactivator BOB.1/OBF.1.
AB  - B cell-specific transcriptional promoter activity mediated by the octamer motif
      requires the Oct1 or Oct2 protein and additional B cell-restricted cofactors. One
      such cofactor, BOB.1/OBF.1, was recently isolated from human B cells. Here, we
      describe the isolation and detailed characterization of the murine homolog. Full
      length cDNAs and genomic clones were isolated, and the gene structure was
      determined. Comparison of the deduced amino acids shows 88% sequence identity
      between mouse and human BOB.1/OBF.1. The NH2-terminal 126 amino acids of
      BOB.1/OBF.1 are both essential and sufficient for interaction with the POU
      domains of either Oct1 or Oct2. This protein-protein interaction does not require
      the simultaneous binding of Oct proteins to DNA, and high resolution footprinting
      of the Oct-DNA interaction reveals that binding of BOB.1/OBF.1 to Oct1 or Oct2
      does not alter the interaction with DNA. BOB.1/OBF.1 can efficiently activate
      octamer-dependent promoters in fibroblasts; however, it fails to stimulate
      octamer-dependent enhancer activity. Fusion of subdomains of BOB.1/OBF.1 with the
      GAL4 DNA binding domain reveals that both NH2- and COOH-terminal domains of
      BOB.1/OBF.1 contribute to full transactivation function, the COOH-terminal domain
      is more efficient in this transactivation assay. Consistent with the failure of
      full-length BOB.1/OBF.1 to stimulate octamer-dependent enhancer elements in non B
      cells, the GAL4 fusions likewise only stimulate from a promoter-proximal
      position.

PMID- 8530385
TI  - N-glycans modulate in vivo and in vitro thyroid hormone synthesis. Study at the N
      terminal domain of thyroglobulin.
AB  - Thyroglobulin (Tg) is the substrate for thyroid hormone biosynthesis, which
      requires tyrosine iodination and iodotyrosine coupling and occurs at the apical
      membrane of the thyrocytes. Tg glycoconjugates have been shown to play a major
      role in Tg routing through cellular compartments and recycling after endocytosis.
      Here we show that glycoconjugates also play a direct role in hormonosynthesis.
      The N-terminal domain (NTD; Asn1-Met171) of human Tg, which bears the
      preferential hormonogenic site, brings two N-glycans (Asn57 and Asn91). NTD
      preparations were purified from Tg with low and mild iodine content in vivo and
      from poorly iodinated Tg after in vitro iodination and coupling. NTD separated
      from poorly iodinated Tg was also submitted to iodination and coupling after
      desialylation and deglycosylation. The various NTD isoforms were analyzed for
      their N-glycan structures and hormone contents. Our results show that 1) in vivo
      as well as in vitro unglycosylated isoforms did not synthesize hormones, whereas
      fully or partially (at Asn91) glycosylated isoforms did; 2) high mannose type
      structures enhanced the hormone content; and 3) desialylation did not affect in
      vitro hormone synthesis. Evidence of a direct involvement in hormonosynthesis
      adds to the role of N-glycans in Tg function and opens the way to new mechanisms
      for regulation (e.g. TSH modulation of N-glycan) or alteration (e.g. Asn91
      mutation) of thyroid hormone synthesis.

PMID- 8530386
TI  - A base substitution within the GTPase-associated domain of mammalian 28 S
      ribosomal RNA causes high thiostrepton accessibility.
AB  - A molecular basis for the insensitivity of eukaryotic ribosomes to the antibiotic
      thiostrepton was investigated using synthetic 100-nucleotide-long fragments
      covering the GTPase domain of 23/28 S rRNA. Filter binding assay showed no
      detectable binding of the rat RNA to thiostrepton, but the binding capacity was
      markedly increased by base substitution of G1878 to A at the position
      corresponding to 1067 of Escherichia coli 23 S rRNA. The association constant (K
      alpha) for the rat A 1878 mutant was 0.60 x 10(6) M-1, which was comparable with
      that of the E. coli RNA (K alpha = 1.1 x 10(6) M-1). This suggests that the
      eukaryotic G 1878 participates in the resistance for thiostrepton. On the other
      hand, the RNA fragments of the two species had a similar binding capacity for E.
      coli ribosomal protein L11 and its mammalian homologue L12. Gel electrophoresis
      under a high ionic condition, however, revealed a difference between the two
      proteins. E. coli L11 formed stable complexes with both the E. coli RNA and the
      rat A 1878 mutant RNA in the presence of thiostrepton, while rat L12 failed to
      exhibit such complex formation. This suggests that the eukaryotic L12 protein may
      also be an element giving the resistance for thiostrepton. These results are
      discussed in terms of preserved three-dimensional conformation of the RNA
      backbone between prokaryotes and higher eukaryotes.

PMID- 8530387
TI  - Stimulation of CTP:phosphocholine cytidylyltransferase by free cholesterol
      loading of macrophages involves signaling through protein dephosphorylation.
AB  - Free cholesterol-loaded macrophages in atheromata synthesize excess
      phosphatidylcholine (PC), which may be an important adaptive response to the
      excess free cholesterol (FC) load. We have recently shown that FC loading of
      macrophages leads to 2-4-fold increases in PC mass and biosynthesis and to the
      post-translational activation of the membrane-bound form of CTP:phosphocholine
      cytidylyltransferase (CT), a key enzyme in PC biosynthesis. Herein, we explore
      further the mechanism of CT activation in FC-loaded macrophages. First,
      enrichment of membranes from control macrophages with FC in vitro did not
      increase CT activity, and PC biosynthesis in vivo is up-regulated by FC loading
      even when CT and FC appear to be mostly in different intracellular sites. These
      data imply that FC activates membrane-bound CT by a signaling mechanism. That the
      proposed signaling mechanism involves structural changes in the CT protein was
      suggested by data showing that two different antibodies against synthetic CT
      peptides showed increased recognition of membrane-bound CT from FC-loaded cells
      despite no increase in CT protein. Since CT is phosphorylated, two-dimensional
      maps of peptides from 32P-labeled control and FC-loaded macrophages were
      compared: six peptide spots from membrane-bound CT, but none from soluble CT,
      were dephosphorylated in the FC-loaded cells. Furthermore, incubation of FC
      loaded macrophages with the phosphatase inhibitor, calyculin A, blocked increases
      in both PC biosynthesis and antipeptide-antibody recognition of CT. Last,
      treatment of membranes from control macrophages with lambda phage protein
      phosphatase in vitro increased both CT activity (2-fold) and antipeptide-antibody
      recognition of CT; soluble CT activity and antibody recognition were not
      substantially affected by phosphatase treatment. In summary, FC loading of
      macrophages leads to the partial dephosphorylation of membrane-bound CT, and
      possibly other cellular proteins, which appears to be important in CT activation.
      This novel regulatory action of FC may allow macrophages to adapt to FC loading
      in atheromata.

PMID- 8530388
TI  - Interaction of wheat germ protein synthesis initiation factor eIF-(iso)4F and its
      subunits p28 and p86 with m7GTP and mRNA analogues.
AB  - The binding of p28, p86, and native wheat germ eIF-(iso)4F with m7GTP and
      oligonucleotides was measured and compared. The purified subunits (p28, 28 kDa
      and p86, 86 kDa) of wheat germ protein synthesis initiation factor eIF-(iso)4F
      have been obtained from Escherichia coli expression of the cloned DNA (van
      Heerden, A., and Browning, K. S. (1994) J. Biol. Chem. 269, 17454-17457). The
      binding of the 5'-terminal cap analogue m7GTP to the small subunit (p28) of eIF
      (iso)4F as a function of pH, temperature, and ionic strength is described. The
      mode of binding of p28 to cap analogues is very similar to the intact protein.
      Assuming that all tryptophan residues contribute to p28 and eIF-(iso)4F
      fluorescence, iodide quenching shows that all 9 tryptophan residues in p28 are
      solvent-accessible, while only 6 out of 16 tryptophan residues are solvent
      accessible on the intact eIF-(iso)4F. The fluorescence stopped-flow studies of
      eIF-(iso)4F and p28 with cap show a concentration-independent conformational
      change. The rate of this conformational change was approximately 10-fold faster
      for the isolated p28 compared with the native eIF-(iso)4F. From these studies it
      appears that cap recognition resides in the p28 subunit. However, p86 enhances
      the interaction with capped oligonucleotides and probably is involved in protein
      protein interactions as well. Both subunits are required for helicase activity.

PMID- 8530389
TI  - Binding of molten globule-like conformations to lipid bilayers. Structure of
      native and partially folded alpha-lactalbumin bound to model membranes.
AB  - The effect of membrane binding on the structure and stability of several
      conformers of alpha-lactalbumin was studied by infrared spectroscopy, circular
      dichroism, and fluorescence spectroscopy. In solution, under experimental
      conditions where all conformers interact with negatively charged membranes, they
      show significant conformational differences. However, binding to negatively
      charged membranes, which causes considerable changes in the structure of these
      conformers, leads to a remarkably similar protein conformation. The membrane
      associated conformations are characterized by 1) a high helical content, greater
      than any of those found in solution, 2) a lack of stable tertiary structure, and
      3) the disappearance of their thermotropic transition. These observations
      indicate that association with negatively charged membranes induces a
      conformational change within alpha-lactalbumin to a flexible, molten globule-like
      state.

PMID- 8530390
TI  - Transcriptional regulation of the cholesteryl ester transfer protein gene by the
      orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1.
AB  - We have defined a 105-base pair tissue-restricted promoter for the cholesteryl
      ester transfer protein (CETP) gene that contains a nuclear hormone receptor
      response element essential for transcriptional activity. DNaseI protection and
      electrophoretic mobility shift assays showed specific binding of nuclear extracts
      from HepG2 (hepatic) and Caco-2 (intestinal) cells (expressing cell types) to 3
      sites (designated A (-26 to -57), B (-59 to -87), and C (-93 to -118)) within the
      105-base pair minimal promoter element between -138 and -33. Mutagenesis studies
      indicated that the function of the promoter was dependent upon synergistic
      interactions between transcription factors bound to these sites. Mutation of site
      C reduced transcription by 50 and 80%, respectively, in HepG2 and Caco-2 cells,
      and electrophoretic mobility shift assays showed that nuclear hormone receptors,
      including ARP-1 and its homologue Ear-3/COUP-TF, were occupants of site C in both
      of these cell types. Overexpression of ARP-1 or Ear-3/COUP-TF with CETP
      promoter/chloramphenicol acetyltransferase gene reporter plasmids repressed
      transcriptional activity of the CETP promoter containing sequences up to -300,
      but activated transcription in the context of larger constructs containing
      sequences up to -636. Thus ARP-1 may assume a dichotomous role as both a
      transcriptional repressor and a transcriptional activator dependent on the
      promoter context. In addition, the architecture of the CETP gene promoter
      suggests that its expression is under the control of multiple transcriptional
      signaling pathways mediated by inducible transcription factors as well as nuclear
      hormone receptors.

PMID- 8530391
TI  - Moricin, a novel type of antibacterial peptide isolated from the silkworm, Bombyx
      mori.
AB  - A novel antibacterial peptide that shows antibacterial activity against
      Staphylococcus aureus was isolated from the hemolymph of the silkworm, Bombyx
      mori. The novel peptide consisted of 42 amino acids and was highly basic. This
      peptide indicated no significant similarity with other antibacterial peptides.
      The peptide showed antibacterial activity against several Gram-negative and 
      positive bacteria and had a higher activity against Gram-positive bacteria than
      cecropin B1, a major antibacterial peptide of B. mori. The novel peptide was
      inducible by bacterial injection. These results suggest that the peptide is
      responsible for the antibacterial activity in B. mori against Gram-positive
      bacteria. The effects of the peptide on bacterial and liposomal membranes showed
      that a target of the peptide is the bacterial cytoplasmic membrane. The results
      also suggest that the N-terminal portion of the peptide, containing a predicted
      alpha-helix, is responsible for an increase in the membrane permeability. We
      propose the name "moricin" for this novel antibacterial peptide isolated from B.
      mori.

PMID- 8530392
TI  - Insulin stimulation of mitogen-activated protein kinase, p90rsk, and p70 S6
      kinase in skeletal muscle of normal and insulin-resistant mice. Implications for
      the regulation of glycogen synthase.
AB  - Skeletal muscles from mice stimulated with insulin in vivo were used to evaluate
      relationships between the insulin receptor tyrosine kinase, mitogen-activated
      protein (MAP) kinase, p90rsk, p70 S6 kinase (p70S6k), and glycogen synthase. Two
      models of insulin resistance were also evaluated: (a) transgenic mice with a
      severe insulin receptor defect and (b) gold thioglucose (GTG) mice (obesity with
      minimal insulin receptor dysfunction). In normal mice, insulin stimulated MAP
      kinase (6-fold), p90rsk (RSK2, 5-fold), p70S6k (10-fold), and glycogen synthase
      (30-50% increase in fractional velocity). In transgenic mice, stimulation of MAP
      kinase and RSK2 were not detectable, whereas activation of p70S6k and glycogen
      synthase were preserved. In GTG mice, activation of MAP kinase, RSK2, p70S6k, and
      glycogen synthase were impaired. Since p70S6k and glycogen synthase were
      correlated, rapamycin was used to block p70S6k, and glycogen synthase activation
      was unaffected in normal mice; however, it was partially impaired in transgenic
      mice. CONCLUSIONS: (a) stimulation of p70S6k and glycogen synthase are
      selectively preserved in muscles with a severe insulin receptor kinase defect,
      indicating signal amplification in pathways leading to these effects; (b) MAP
      kinase-RSK2 and p70S6k activation are impaired in obese mice, suggesting multiple
      loci for postreceptor insulin resistance; (c) glycogen synthase was dissociated
      from MAP kinase and RSK2, indicating that they are not required for this effect
      of insulin; and (d) p70S6k is not essential for glycogen synthase activation, but
      it may participate in redundant signaling pathways leading to this effect of
      insulin.

PMID- 8530393
TI  - Kinetic characterization of channel impaired mutants of tryptophan synthase.
AB  - Tryptophan synthase, an alpha 2 beta 2 tetrameric complex, is a classic example
      of an enzyme that is thought to "channel" a metabolic intermediate (indole) from
      the active site of the alpha subunit to the active site of the beta subunit. The
      solution of the three-dimensional structure of the enzyme from Salmonella
      typhimurium provided physical evidence for a 25-A hydrophobic tunnel which
      connects the alpha and beta active sites (Hyde, C. C., Ahmed, S. A., Padlan, E.
      A., Miles, E. W., and Davies, D. R. (1988) J. Biol. Chem. 263, 17857-17871).
      Using rapid reaction kinetics, we have previously established that indole is
      indeed channeled and have identified three essential kinetic features which
      govern efficient channeling. In the current study we have probed the necessity of
      these features by using site-directed mutagenesis to alter these requirements. We
      now report the kinetic characterization of two mutants which contain
      substitutions to block or restrict the tunnel (beta C170F and beta C170W).
      Preliminary kinetic and structural evidence of a restricted tunnel in the beta
      C170W has been provided (Schlichting, I., Yang, X. W., Miles, E. W., Kim, A. Y.,
      and Anderson, K. S. (1994) J. Biol. Chem. 269, 26591-26593). The rapid kinetic
      analysis of these mutant proteins shows that these mutations interfere with
      efficient channeling of the indole metabolite such that indole can be observed in
      single enzyme turnover of the physiologically relevant alpha beta reaction. In
      addition, the beta C170W mutant appears to be impaired in alpha beta intersubunit
      communication.

PMID- 8530394
TI  - Bending and torsional flexibility of G/C-rich sequences as determined by
      cyclization assays.
AB  - The structural polymorphism of DNA is a vital aspect of its biological function.
      However, it has become increasingly apparent in recent years that DNA
      polymorphism is a complicated, multidimensional phenomenon that includes not only
      static sequence-directed structures but dynamic effects as well, including
      influences of counterions and sequence context. In order to address some of these
      additional factors that govern DNA conformation, we have used T4 ligase-mediated
      cyclization to investigate bending in a series of DNA sequences containing the
      GGGCCC.GGGCCC motif in different sequence contexts including various helical
      phasings with (A)5-tracts. We present evidence for curvature in GGGCCC.GGGCCC and
      (A)5-tract motifs in the presence of physiological levels of Mg2+ and show that
      these motifs curve through similar but oppositely directed bending angles under
      these ionic strength conditions. Although these two sequence motifs appear to
      bend similarly, our results suggest significant differences in stiffness and
      stability of curvature between them. We also show that under the same
      experimental conditions, the CTAG-CTAG sequence element possesses unusual
      torsional flexibility and that this appears to be associated with the central
      TA.TA dinucleotide. The results underscore the need to include sequence context
      and specific ion effects as well as a dynamic basis in more complete predictive
      models for functionally related DNA polymorphism.

PMID- 8530395
TI  - Kinetics of acid-mediated disassembly of the B subunit pentamer of Escherichia
      coli heat-labile enterotoxin. Molecular basis of pH stability.
AB  - The B-subunit pentamer of Escherichia coli heat-labile enterotoxin (EtxB) is
      highly stable, maintaining its quaternary structure in a range of conditions that
      would normally be expected to cause protein denaturation. In this paper the
      structural stability of EtxB has been studied as a function of pH by
      electrophoretic, immunochemical, and spectroscopic techniques. Disassembly of the
      cyclic pentameric structure of human EtxB occurs only below pH 2. As determined
      by changes in intrinsic fluorescence this process follows first-order kinetics,
      with the rate constant for disassembly being proportional to the square of the H+
      ion concentration, and with an activation energy of 155 kJ mol-1. A C-terminal
      deletion mutant, hEtxB214, similarly shows first-order kinetics for disassembly
      but with a higher pH threshold, resulting in disassembly being seen at pH 3.4 and
      below. These findings are consistent with the rate-limiting step for disassembly
      of human EtxB being the simultaneous disruption of two interfaces by protonation
      of two C-terminal carboxylates. By comparison, disassembly of the B-subunit of
      cholera toxin (CtxB), a protein which shows 80% sequence identity with EtxB,
      exhibits a much lower stability to acid conditions; with disassembly of CtxB
      occurring below pH 3.9, with an activation energy of 81 kJ mol-1. Reasons for the
      observed differences in acid stability are discussed, and the implications of
      these findings to the development of oral vaccines using EtxB and CtxB are
      considered.

PMID- 8530396
TI  - The role of threonine 54 in adrenodoxin for the properties of its iron-sulfur
      cluster and its electron transfer function.
AB  - The amino acid in position 54 of adrenodoxin is strongly conserved among
      ferredoxins, consisting of a threonine or serine. Its role was studied by
      analyzing mutants T54S and T54A of bovine adrenodoxin. Absorption, circular
      dichroism, fluorescence, and electron paramagnetic resonance spectra of mutant
      T54S show that this substitution has no influence on the formation and stability
      of the ferredoxin. The redox potential of this mutant, however, was lowered by 55
      mV as compared with native adrenodoxin, indicating a role for this residue in
      redox potential modulation. Incorporation of the iron-sulfur cluster was not
      impaired in the T54A mutant, although structural features of the oxidized protein
      were considerably changed. The decreased stability of the T54A mutant as compared
      with the wild type and mutant T54S indicates that a hydrogen bond donor at this
      position stabilizes the protein. Both mutants have been shown to be functionally
      active. Replacement of threonine 54 by serine or alanine, however, leads to
      rearrangements at the recognition sites for its redox partners. This is reflected
      by decreased Km and Kd values of both mutants for the cytochromes P450, whereas
      only T54A displayed a decreased Km value in cytochrome c reduction. Substrate
      conversion was accelerated (2.2- and 2.4-fold for mutants T54A and T54S,
      respectively) in the CYP11B1-, but not in the CYP11A1-dependent reaction.

PMID- 8530397
TI  - Pharmacological induction of heat shock protein 68 synthesis in cultured rat
      astrocytes.
AB  - The induction of the highly inducible 70-kDa heat shock protein (HSP 70) is
      associated with thermotolerance and survival from many other types of stress.
      This investigation studied the pharmacological induction of HSP 68 (HSP 68 is the
      rat homolog of human HSP 70) by 1,10-phenanthroline in cultured rat astrocytes
      under conditions that activated heat shock transcription factor-1 without
      inducing HSP 68 synthesis. Two conditions that activate heat shock transcription
      factor-1 and promote its binding to the heat shock element without subsequent
      transcription of HSP 68 mRNA, intracellular acidosis and exposure to salicylate,
      showed synthesis of HSP 68 when 1,10-phenanthroline was added to culture medium
      after the activation of heat shock transcription factor-1. 1,10-phenanthroline
      mimicked heat shock by inducing HSP 68 mRNA and protein under both conditions.
      1,10-phenanthroline added alone to culture medium did not induce the synthesis of
      HSP 68 or activate heat shock transcription factor-1. These findings strongly
      suggest a multistep activation for HSP 68 synthesis and also demonstrate that the
      synthesis of HSP 68 can be pharmacologically regulated.

PMID- 8530398
TI  - Identification of a binding motif for ankyrin on the alpha-subunit of Na+,K(+)
      ATPase.
AB  - Cytoskeleton membrane associations are important for a variety of cellular
      functions. The anion exchanger of erythrocytes (AE1) and Na+,K(+)-ATPase of
      polarized epithelial cells provide well studied examples of how integral membrane
      proteins are anchored via the linker molecule ankyrin to the spectrin-based
      membrane cytoskeleton. In the present study we have generated several recombinant
      fragments of the large (third) cytoplasmic domain (CD3) of Na+,K(+)-ATPase to
      define binding sites of ankyrin on CD3 at a molecular level. We provide evidence
      that a cluster of four amino acids, ALLK, is essential for binding of ankyrin to
      both recombinant CD3 and to native Na+,K(+)-ATPase. Once bound, conformational
      changes might uncover further binding sites for ankyrin on Na+,K(+)-ATPase. A
      motif related to the ALLK cluster is also present in the cytoplasmic domain of
      AE1 where this sequence (ALLLK) turned out to be also important for ankyrin
      binding. These motifs are highly conserved during evolution of both Na+,K(+)
      ATPase and AE1, further underlining their potential role in cytoskeleton to
      membrane linkage.

PMID- 8530399
TI  - The transcriptional effect of WT1 is modulated by choice of expression vector.
AB  - The WT1 Wilms' tumor suppressor gene encodes a zinc finger transcription factor
      which plays a critical role in renal and genitourinary development. The WT1
      protein was reported to both activate and repress transcription. We found that
      the transcriptional effect of WT1 on the Egr1 promoter could be modulated by the
      use of expression vectors containing different promoters. WT1 activated the Egr1
      promoter when expression of WT1 was driven by the Rous sarcoma virus promoter. In
      contrast, a cytomegalovirus (CMV) promoter-containing WT1 expression vector
      repressed the Egr1 promoter. However, WT1 activated transcription of a simple
      test promoter, EGR3tkCAT, regardless of the expression vector used. Co
      transfection of the parental CMV-based vector strongly depressed the basal
      activity of the Egr1-CAT reporter, suggesting that the CMV promoter competes with
      the Egr1 promoter for transcription factors or co-factors which may be required
      for activation by WT1. In support of this hypothesis, WT1 was converted from an
      activator to a repressor by co-transfection of an excess of the parental CMV
      based vector. These results provide an important caveat to the interpretation of
      co-transfection studies and confirm the bi-functional nature of the WT1
      transcription factor.

PMID- 8530400
TI  - Evidence for an anti-parallel orientation of the ligand-activated human androgen
      receptor dimer.
AB  - Domain interactions of the human androgen receptor (AR) dimer were investigated
      using a protein-protein interaction assay in which the NH2- and carboxyl-terminal
      regions of human AR were fused to the Saccharomyces cerevisiae GAL4 DNA-binding
      domain and herpes simplex virus VP16 transactivation domain to produce chimeric
      proteins. Transcriptional activation of a GAL4 luciferase reporter vector up to
      100-fold was greater than Fos/Jun leucine zipper binding, indicating stable AR
      interaction between AR NH2-terminal residues 1-503 and steroid-binding domain
      residues 624-919 that was specific for and dependent on androgen binding to the
      steroid-binding domain and was inhibited by anti-androgen binding. Deletion
      mutagenesis within the NH2-terminal region indicated transactivation domain
      residues 142-337 were not required for dimerization, whereas deletions near the
      NH2 terminus (delta 14-150) or NH2-terminal to the DNA-binding domain (delta 339
      499) reduced or eliminated the AR interaction, respectively. An NH2-/NH2-terminal
      interaction was also observed, but no interaction was detected between ligand
      free or bound steroid-binding domains. The results indicate that high affinity
      androgen binding promotes interactions between the NH2-terminal and steroid
      binding domains of human AR, raising the possibility of an androgen-induced anti
      parallel AR dimer.

PMID- 8530401
TI  - A physiological role for Saccharomyces cerevisiae copper/zinc superoxide
      dismutase in copper buffering.
AB  - The copper toxicity of yeast lacking the CUP1 metallothionein is suppressed by
      overexpression of the CRS4 gene. We now demonstrate that CRS4 is equivalent to
      SOD1, encoding copper/zinc superoxide dismutase (SOD). While overexpression of
      SOD1 enhanced copper resistance, a deletion of SOD1, but not SOD2 (encoding
      manganese SOD), conferred an increased sensitivity toward copper. This role of
      SOD1 in copper buffering appears unrelated to its superoxide scavenging activity,
      since the enzyme protected against copper toxicity in anaerobic as well as
      aerobic conditions. The distinct roles of SOD1 in copper and oxygen radical
      homeostasis could also be separated genetically: the pmr1, bsd2, and ATX1 genes
      that suppress oxygen toxicity in sod1 mutants failed to suppress the copper
      sensitivity of these cells. The Saccharomyces cerevisiae SOD1 gene is
      transcriptionally induced by copper and the ACE1 transactivator, and we
      demonstrate here that this induction of SOD1 promotes protection against copper
      toxicity but is not needed for the SOD1-protection against oxygen free radicals.
      Collectively, these findings indicate that copper/zinc SOD functions in the
      homeostasis of copper via mechanisms distinct from superoxide scavenging.

PMID- 8530402
TI  - Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an
      acute phase response and bind interleukin-6 response elements.
AB  - Proteins binding at the interleukin-6 response element of the rat alpha 2
      macroglobulin gene were purified by a combination of chromatographic procedures
      including binding site-specific DNA-affinity chromatography as the principal
      step. Three polypeptides of 92, 91, and 86 kDa were enriched approximately 6,300
      fold from nuclei of rat livers excised 12 h after the induction of an
      experimental acute phase response. Amino acid sequence analysis identified the 86
      and 91-kDa species as two forms of the transcription factor Stat3 and the 92-kDa
      species as the factor Stat5b. This identification was confirmed by gel mobility
      shift-supershift experiments using specific antisera for Stat3 and Stat5.
      Unexpectedly, activated Stat5 was also detected in the nuclei of untreated
      control rats. cDNA clones representing Stat3 and two isoforms of Stat5b were
      isolated from a cDNA library prepared with mRNA from rat livers excised at the
      peak of an experimental acute phase response. Full-length Stat5b, predicted from
      cDNA, consisted of 786 amino acids, while the variant Stat5b delta 40C lacked 41
      amino acids at the COOH terminus. The amino acid sequence of rat Stat5b showed
      26.7% overall identity with rat Stat3, 87.3% with sheep Stat5a, 92.5% with murine
      Stat5a, and 98.7% with murine Stat5b.

PMID- 8530403
TI  - Role of the catalytic serine in the interactions of serine proteinases with
      protein inhibitors of the serpin family. Contribution of a covalent interaction
      to the binding energy of serpin-proteinase complexes.
AB  - The contribution of a covalent bond to the stability of complexes of serine
      proteinases with inhibitors of the serpin family was evaluated by comparing the
      affinities of beta-trypsin and the catalytic serine-modified derivative, beta
      anhydrotrypsin, for several serpin and non-serpin (Kunitz) inhibitors. Kinetic
      analyses showed that anhydrotrypsin had little or no ability to compete with
      trypsin for binding to alpha 1-proteinase inhibitor (alpha 1PI), plasminogen
      activator inhibitor 1 (PAI-1), antithrombin (AT), or AT-heparin complex when
      present at up to a 100-fold molar excess over trypsin. By contrast, equimolar
      levels of anhydrotrypsin blocked trypsin binding to non-serpin inhibitors.
      Equilibrium binding studies of inhibitor-enzyme interactions monitored by
      inhibitor displacement of the fluorescence probe, p-aminobenzamidine, from the
      enzyme active site, confirmed that the binding of serpins to anhydrotrypsin was
      undetectable in the case of alpha 1PI or AT (KI > 10(-5) M), of low affinity in
      the case of AT-heparin complex (KI 7-9 x 10(-6) M), and of moderate affinity in
      the case of PAI-1 (KI 2 x 10(-7) M). This contrasted with the stoichiometric high
      affinity binding of the serpins to trypsin as well as of the non-serpin
      inhibitors to both trypsin and anhydrotrypsin. Maximal KI values for serpin
      trypsin interactions of 1 to 8 x 10(-11) M, obtained from kinetic analyses of
      association and dissociation rate constants, indicated that the affinity of
      serpins for trypsin was minimally 4 to 6 orders of magnitude greater than that of
      anhydrotrypsin. Anhydrotrypsin, unlike trypsin, failed to induce the
      characteristic fluorescence changes in a P9 Ser-->Cys PAI-1 variant labeled with
      a nitrobenzofuran fluorescent probe (NBD) which were shown previously to report
      the serpin conformational change associated with active enzyme binding. These
      results demonstrate that a covalent interaction involving the proteinase
      catalytic serine contributes a major fraction of the binding energy to serpin
      trypsin interactions and is essential for inducing the serpin conformational
      change involved in the trapping of enzyme in stable complexes.

PMID- 8530404
TI  - Insulin-induced activation of phosphatidylinositol (PI) 3-kinase. Insulin-induced
      phosphorylation of insulin receptors and insulin receptor substrate-1 displaces
      phosphorylated platelet-derived growth factor receptors from binding sites on PI
      3-kinase.
AB  - Phosphatidylinositol (PI) 3-kinase is an enzyme that functions in the signaling
      pathways downstream from multiple cell surface receptors. The p85 regulatory
      subunit of PI 3-kinase binds to phosphotyrosine residues of various
      phosphoproteins including the platelet-derived growth factor (PDGF) receptor, the
      insulin receptor, and insulin receptor substrate-1 (IRS-1). Using NIH-3T3 cells
      overexpressing the human insulin receptor, we demonstrate that the p85 regulatory
      subunit of PI 3-kinase binds to phosphorylated PDGF receptor in cells incubated
      in the absence of insulin. When insulin is added, p85 is released from
      phosphorylated PDGF receptors and binds to phosphorylated insulin receptors and
      insulin receptor substrate-1. Moreover, insulin-induced dissociation of PDGF
      receptors from binding sites on PI 3-kinase requires a functional insulin
      receptor and is not prevented by vanadate treatment. In contrast, insulin
      activation does not displace PDGF receptors from binding sites on Ras GTPase
      activating protein. This competition for binding to PI 3-kinase provides a
      mechanism for cross-talk among signaling pathways initiated by distinct peptide
      hormones and growth factors such as insulin and PDGF.

PMID- 8530405
TI  - Identification of two amino acid residues on the extracellular domain of the
      lutropin/choriogonadotropin receptor important in signaling.
AB  - The lutropin/choriogonadotropin receptor (LH/CG-R) is a G protein-coupled
      receptor with a relatively large extracellular domain. The cDNAs of LH/CG-R wild
      type and 15 point and double mutants, which encoded residues of opposite charge
      to that of wild type, were transiently transfected into COS-7 cells. Human
      choriogonadotropin (hCG) binding was determined, as was hCG-mediated cAMP
      production. Most of the replacements resulted in no substantive effect on the
      binding affinity of hCG to LH/CG-R or on hCG-stimulated cAMP production, although
      the mutants expressed at a lower level than LH/CG-R wild type. The most
      interesting observation was noted with two point mutants of LH/CG-R, Glu332-->Lys
      and Asp333-->Lys, which bound hCG but failed to give increased cAMP production.
      Several of the mutant forms of LH/CG-R that expressed at low levels were further
      analyzed by soluble binding assays and Western blots. There was no evidence of
      any significant degree of intracellular trapping of hCG-binding mutant receptors.
      The expected major (93 kDa) and minor (78 kDa) forms were found for LH/CG-R wild
      type and several of the mutants. The Lys235-->Asp and Asp333-->Lys mutants
      exhibited primarily the lower M(r) form, indicating that receptor processing was
      impaired or that the mutant higher M(r) form was more rapidly degraded than LH/CG
      R wild type. These results demonstrate that Glu332 and Asp333, which are located
      near the first transmembrane helix, are important in receptor activation, while
      other conserved ionizable residues of LH/CG-R appear important in cell surface
      expression or stability but not in binding or signaling.

PMID- 8530406
TI  - The mouse fkh-2 gene. Implications for notochord, foregut, and midbrain
      regionalization.
AB  - The "winged helix" or "forkhead" transcription factors comprise a large gene
      family whose members are defined by a common 100-amino acid DNA binding domain.
      Here we describe the structure and expression of the mouse fkh-2 gene, which
      encodes a protein of 48 kDa with high similarity to other winged helix
      transcription factors within the DNA binding region, but unique potential
      transactivation domains. The gene is encoded by a single exon and is expressed in
      headfold stage embryos in the notochord, the anterior neuroectoderm, and a few
      cells of the definite endoderm. This expression becomes restricted to the
      anteriormost portions of the invaginating foregut and the developing midbrain.
      From day 11.5 of gestation onward, fkh-2 transcripts are restricted to the
      midbrain and become progressively localized to the red nuclei as the sole site of
      expression. The fkh-2 gene maps to chromosome 19B and is a candidate gene for the
      mouse mutation mdf (muscle-deficient) which is characterized by nervous tremors
      and degeneration of the hindlimb muscles. Although the expression patterns of the
      fkh-2 gene and another winged helix protein, HNF-3 beta, are overlapping in early
      stages of gestation and although the promoter of the fkh-2 gene contains a HNF-3
      binding site, we demonstrate that the activation of the fkh-2 gene is independent
      of HNF-3 beta.

PMID- 8530407
TI  - Roles of a membrane-localized beta subunit in the formation and targeting of
      functional L-type Ca2+ channels.
AB  - We report several unexpected findings that provide novel insights into the
      properties and interactions of the alpha 1 and beta subunits of dihydropyridine
      sensitive L-type channels. First, the beta 2a subunit was expressed as multiple
      species of 68-72 kDa; the 70-72-kDa species arose from post-translational
      modification. Second, cell fractionation and immunocytochemical studies indicated
      that the hydrophilic beta 2a subunit, when expressed alone, was membrane
      localized. Third, the beta 2a subunit increased the membrane localization of the
      alpha 1 subunit and the number of cells expressing L-type Ca2+ currents, without
      affecting the total amount of the expressed alpha 1C subunit. Expression of
      maximal currents in alpha 1C/beta 2a cotransfected cells paralleled the time
      course of expression of the beta subunit. Taken together, these results suggest
      that the beta subunit plays multiple roles in the formation, stabilization,
      targeting, and modulation of L-type channels.

PMID- 8530409
TI  - Analysis of three DnaK mutant proteins suggests that progression through the
      ATPase cycle requires conformational changes.
AB  - DnaK, the bacterial homolog of the eukaryotic hsp70 proteins, is an ATP-dependent
      chaperone whose basal ATPase is stimulated by synthetic peptides and its cohort
      heat shock proteins, DnaJ and GrpE. We have used three mutant DnaK proteins,
      E171K, D201N, and A174T (corresponding to Glu175, Asp206, and Ala179,
      respectively, in bovine heat stable cognate 70) to probe the ATPase cycle. All of
      the mutant proteins exhibit some alteration in basal ATP hydrolysis. However,
      they all exhibit more severe defects in the regulated activities. D201N and E171K
      are completely defective in all regulated activities of the protein and also in
      making the conformational change exhibited by the wt protein upon binding ATP. We
      suggest that the inability of D201N and E171K to achieve the ATP activated
      conformation prevents both stimulation by all effectors and the ATP-mediated
      release of GrpE. In contrast, the defect of A174T is much more specific. It
      exhibits normal binding and release of GrpE and normal stimulation of ATPase
      activity by DnaJ. However, it is defective in the synergistic activation of its
      ATPase by DnaJ and GrpE. We suggest that this mutant protein is specifically
      defective in a DnaJ/GrpE mediated conformational change in DnaK necessary for the
      synergistic action of DnaJ+GrpE.

PMID- 8530408
TI  - Regulatory role of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in
      insulin secretion by glucose in pancreatic beta cells. Enhanced insulin secretion
      in CD38-expressing transgenic mice.
AB  - Cyclic ADP-ribose (cADPR) serves as a second messenger for Ca2+ mobilization in
      insulin secretion, and CD38 has both ADP-ribosyl cyclase and cADPR hydrolase
      activities (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto,
      T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here,
      we produced transgenic mice overexpressing human CD38 in pancreatic beta cells.
      The enzymatic activity of CD38 in transgenic islets was greatly increased, and
      ATP efficiently inhibited the cADPR hydrolase activity. The Ca2+ mobilizing
      activity of cell extracts from transgenic islets incubated in high glucose was 3
      fold higher than that of the control, suggesting that ATP produced by glucose
      metabolism increased cADPR accumulation in transgenic islets. Glucose- and
      ketoisocaproate-induced but not tolbutamide- nor KCl-induced insulin secretions
      from transgenic islets were 1.7-2.3-fold higher than that of control. In glucose
      tolerance tests, the transgenic serum insulin level was higher than that of
      control. The present study provides the first evidence that CD38 has a regulatory
      role in insulin secretion by glucose in beta cells, suggesting that the Ca2+
      release from intracellular cADPR-sensitive Ca2+ stores as well as the Ca2+ influx
      from extracellular sources play important roles in insulin secretion.

PMID- 8530410
TI  - Isolation and characterization of a novel perchloric acid-soluble protein
      inhibiting cell-free protein synthesis.
AB  - We found a novel protein in the postmitochondria supernatant fraction of rat
      liver, which is soluble in 5% perchloric acid and strongly inhibits protein
      synthesis in a rabbit reticulocyte lysate system. The protein extracted from the
      supernatant fraction with 5% perchloric acid was purified by ammonium sulfate
      fractionation and CM-Sephadex chromatography. The protein was shown to consist of
      two identical subunits with a molecular mass of 14 kDa. By immunoscreening with
      the rabbit antisera against the protein, a cDNA encoding the protein was cloned
      and sequenced. The cDNA contained an open reading frame of 411 base pairs
      encoding a 136-amino acid protein with a molecular mass of 14,149 Da. The deduced
      amino acid sequence was completely identical with that constructed from all of
      the above peptides. Interestingly, the perchloric acid-soluble protein inhibited
      cell-free protein synthesis in the rabbit reticulocyte lysate system in a
      different manner from RNase A. The protein is likely to inhibit an initiation
      stage of cell-free protein synthesis. Among the rat tissues tested, the protein
      was located only in liver and kidney. These findings are the first report on a
      new inhibitor that may be involved in the regulation of protein synthesis in
      those tissues.

PMID- 8530411
TI  - The G protein beta gamma subunit transduces the muscarinic receptor signal for
      Ca2+ release in Xenopus oocytes.
AB  - At least 30 G protein-linked receptors stimulate phosphatidylinositol 4,5
      bisphosphate phosphodiesterase (phospholipase C beta, PLC beta) through G protein
      subunits to release intracellular calcium from the endoplasmic reticulum
      (Clapham, D. E. (1995) Cell 80, 259-268). Although both G alpha and G beta gamma
      G protein subunits have been shown to activate purified PLC beta in vitro, G
      alpha q has been presumed to mediate the pertussis toxin-insensitive response in
      vivo. In this study, we show that G beta gamma plays a dominant role in
      muscarinic-mediated activation of PLC beta by employing the Xenopus oocyte
      expression system. Antisense nucleotides and antibodies to G alpha q/11 blocked
      the m3-mediated signal transduction by inhibiting interaction of the muscarinic
      receptor with the G protein. Agents that specifically bound free G beta gamma
      subunits (G alpha-GDP and a beta-adrenergic receptor kinase fragment) inhibited
      acetylcholine-induced signal transduction to PLC beta, and injection of G beta
      gamma subunits into oocytes directly induced release of intracellular Ca2+. We
      conclude that receptor coupling specificity of the G alpha q/G beta gamma
      heterotrimer is determined by G alpha q; G beta gamma is the predominant
      signaling molecule activating oocyte PLC beta.

PMID- 8530412
TI  - Phosphorylation of the cytosolic domain of peptidylglycine alpha-amidating
      monooxygenase.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme that
      catalyzes the COOH-terminal alpha-amidation of neural and endocrine peptides
      through a two-step reaction carried out sequentially by its monooxygenase and
      lyase domains. PAM occurs in soluble and integral membrane forms. Metabolic
      labeling of stably transfected hEK-293 and AtT-20 cells showed that [32P]PO4(3-)
      was efficiently incorporated into Ser and Thr residues of membrane PAM but not
      into soluble PAM. Truncation of integral membrane PAM proteins (which terminate
      with Ser976) at Tyr936 eliminated their phosphorylation, suggesting that the COOH
      terminal region of the protein was the site of phosphorylation. Recombinant PAM
      COOH-terminal domain was phosphorylated on Ser932 and Ser937 by protein kinase C
      (PKC). PAM-1 protein recovered from different subcellular fractions of stably
      transfected AtT-20 cells was differentially susceptible to calcium-dependent,
      staurosporine-inhibitable phosphorylation catalyzed by endogenous cytosolic
      protein kinase(s). Although phorbol ester treatment of hEK-293 cells expressing
      PAM-1 stimulated the cleavage/release of a bifunctional 105-kDa PAM protein, the
      effect was an indirect one since it was also observed in hEK-293 cells expressing
      a truncated PAM-1 protein that was not phosphorylated. AtT-20 cells expressing
      PAM-1 lacking one of the PKC sites (PAM-1/Ser937-->Ala) exhibited an altered
      pattern of PAM.PAM antibody internalization, with the mutant protein targeted to
      lysosomes upon internalization. Thus, phosphorylation of Ser937 in the COOH
      terminal cytosolic domain of membrane PAM plays a role in a specific step in the
      targeting of this protein.

PMID- 8530413
TI  - Ischemia and reperfusion enhance ATF-2 and c-Jun binding to cAMP response
      elements and to an AP-1 binding site from the c-jun promoter.
AB  - The transcription factors controlling the complex genetic response to ischemia
      and their modes of regulation are poorly understood. We found that ATF-2 and c
      Jun DNA binding activity is markedly enhanced in post-ischemic kidney or in LLC
      PK1 renal tubular epithelial cells exposed to reversible ATP depletion. After 40
      min of renal ischemia followed by reperfusion for as little as 5 min, binding of
      ATF-2 and c-Jun, but not ATF-3 or CREB (cAMP response element binding protein),
      to oligonucleotides containing either an ATF/cAMP response element (ATF/CRE) or
      the jun2TRE from the c-jun promoter, was significantly increased. Binding to
      jun2TRE and ATF/CRE oligonucleotides occurred with an identical time course. In
      contrast, nuclear protein binding to an oligonucleotide containing a canonical AP
      1 element was not detected until 40 min of reperfusion, and although c-Jun was
      present in the complex, ATF-2 was not. Incubating nuclear extracts from
      reperfused kidney with protein phosphatase 2A markedly reduced binding to both
      the ATF/CRE and jun2TRE oligonucleotides, compatible with regulation by an ATF-2
      kinase. An ATF-2 kinase, which phosphorylated both the transactivation and DNA
      binding domains of ATF-2, was activated by reversible ATP depletion. This kinase
      coeluted on Mono Q column chromatography with a c-Jun amino-terminal kinase and
      with the peak of stress-activated protein kinase, but not p38, immunoreactivity.
      In conclusion, DNA binding activity of ATF-2 directed at both ATF/CRE and jun2TRE
      motifs is modulated in response to the extreme cellular stress of ischemia and
      reperfusion or reversible ATP depletion. Phosphorylation-dependent activation of
      the DNA binding activity of ATF-2, which appears to be regulated by the stress
      activated protein kinases, may play an important role in the earliest stages of
      the genetic response to ischemia/reperfusion by targeting ATF-2 and c-Jun to
      specific promoters, including the c-jun promoter and those containing ATF/CREs.

PMID- 8530414
TI  - Delayed mammary tumor progression in Muc-1 null mice.
AB  - The mucin gene, Muc-1, encodes a high molecular weight integral membrane
      glycoprotein that is present on the apical surface of most simple secretory
      epithelial cells. Muc-1 is highly expressed and aberrantly glycosylated by most
      carcinomas and metastatic lesions. Numerous functions have been proposed for this
      molecule, including protection of the epithelial cell surface, an involvement in
      epithelial organogenesis, and a role in tumor progression. Mice deficient in Muc
      1 were generated using homologous recombination in embryonic stem cells. These
      mice appeared to develop normally and were healthy and fertile. However, the
      growth rate of primary breast tumors induced by polyoma middle T antigen was
      found to be significantly slower in Muc-1 deficient mice. This suggests that Muc
      1 plays an important role in the progression of mammary carcinoma.

PMID- 8530416
TI  - Mutants in the putative nucleotide-binding region of the plasma membrane Ca(2+)
      pump. A reduction in activity due to slow dephosphorylation.
AB  - Mutants of individual residues of the plasma membrane Ca(2+)-pump were made in
      the highly conserved region that (in related P-type ATPases) has been associated
      with nucleotide binding. Alteration of the strictly conserved Asp672 to Glu
      nearly eliminated the ability of the pump to transport Ca2+, while alteration at
      Val674, Arg675, and Lys686 reduced the activity. High levels of ATP (25 mM) did
      not overcome the reduced activity, indicating that it could not be due to a
      reduction in the affinity for ATP. Effects not directly related to ATP binding
      seemed to result from mutations in this area. For instance, the amount of
      phosphorylated intermediate in the most severely inhibited mutant, Asp672-->Glu,
      was nearly as high as that in the wild type, a much larger amount of
      phosphorylated intermediate than was expected from its low activity. However, the
      rate of decomposition of this intermediate was much slower than that of the wild
      type, indicating that the inhibition of this mutant resulted from an inhibition
      of the E approximately P-->E step in the enzyme cycle.

PMID- 8530415
TI  - Identification of two isoforms of mouse neuropeptide Y-Y1 receptor generated by
      alternative splicing. Isolation, genomic structure, and functional expression of
      the receptors.
AB  - Two cDNA clones homologous with human neuropeptide (NP) Y-Y1 receptor have been
      isolated from a mouse bone marrow cDNA library. One was thought to be the cognate
      of the human NPY-Y1 receptor, termed Y1 alpha receptor, and the other form,
      termed Y1 beta receptor, differed from the Y1 alpha receptor in the seventh
      transmembrane domain and C-terminal tail. Analysis of the mouse genomic DNA
      showed that both receptors originated from a single gene. The different peptide
      sequences of the Y1 beta receptor were encoded by separate exons, hence, these
      receptors were generated by differential RNA splicing. High affinity binding of
      [125I]NPY to each receptor expressed in Chinese hamster ovary (CHO) cells and
      sequestration of [125I]NPY after binding to each receptor were observed. In the
      CHO cells expressing the Y1 alpha receptor, intracellular Ca2+ increase,
      inhibition of forskolin-induced cAMP accumulation, and mitogen-activated protein
      kinase (MAPK) activation were observed by stimulation of NPY, and these responses
      were abolished by pretreatment with pertussis toxin. Since wortmannin completely
      inhibited NPY-elicited MAPK activation, we speculate that wortmannin-sensitive
      signaling molecule(s) such as phosphoinositide 3-kinase may lie between pertussis
      toxin-sensitive G-protein and MAPK. In contrast, these intracellular signals were
      not detected in CHO cells expressing the Y1 beta receptor. Northern blots and
      reverse transcriptase-polymerase chain reaction analyses indicated that the Y1
      alpha receptor was highly expressed in the brain, heart, kidney, spleen, skeletal
      muscle, and lung, whereas the Y1 beta receptor mRNA was not detected in these
      tissues. However, the Y1 beta receptor was expressed in mouse embryonic
      developmental stage (7 and 11 days), bone marrow cells and several hematopoietic
      cell lines. These results suggest that the Y1 beta receptor is an embryonic and a
      bone marrow form of the NPY-Y1 receptor, which decreases in the expression during
      development and differentiation.

PMID- 8530417
TI  - Phorbol ester regulation of opioid peptide gene expression in myocardial cells.
      Role of nuclear protein kinase.
AB  - Opioid peptide gene expression was characterized in adult rat ventricular cardiac
      myocytes that had been cultured in the absence or the presence of phorbol 12
      myristate 13-acetate. The phorbol ester induced a concentration- and time
      dependent increase of prodynorphin mRNA, the maximal effect being reached after 4
      h of treatment. The increase in mRNA expression was suppressed by incubation of
      cardiomyocytes with staurosporine, a putative protein kinase C inhibitor, and was
      not observed when the cells were cultured in the presence of the inactive phorbol
      ester 4 alpha-phorbol 12,13-didecanoate. Incubation of cardiac myocytes with
      phorbol 12-myristate 13-acetate also elicited a specific and staurosporine
      sensitive increase in immunoreactive dynorphin B, a biologically active end
      product of the precursor, both in the myocardial cells and in the culture medium.
      In vitro run-off transcription assays indicated that transcription of the
      prodynorphin gene was increased both in nuclei isolated from phorbol ester
      treated myocytes and in nuclei isolated from control cells and then exposed to
      phorbol 12-myristate 13-acetate. No transcriptional effect was observed when
      cardiac myocytes or isolated nuclei where exposed to 4 alpha-phorbol 12,13
      didecanoate. The phorbol ester-induced increase in prodynorphin gene
      transcription was prevented by pretreatment of myocytes or isolated nuclei with
      staurosporine, suggesting that myocardial opioid gene expression may be regulated
      by nuclear protein kinase C. In this regard, cardiac myocytes expressed protein
      kinase C-alpha, -delta, -epsilon, and -zeta, as shown by immunoblotting. Only
      protein kinase C-delta and protein kinase C-epsilon were expressed in nuclei that
      have been isolated from control myocytes, suggesting that these two isotypes of
      the enzyme may be part of the signal transduction pathway involved in the effect
      elicited by the phorbol ester on opioid gene transcription in isolated nuclei.
      The incubation of myocardial nuclei isolated from control cells in the presence
      of a protein kinase C activator induced the phosphorylation of the myristoylated
      alanine-rich protein kinase C substrate peptide, a specific fluorescent substrate
      of the enzyme. The possibility that prodynorphin gene expression may control the
      heart function through autocrine or paracrine mechanisms is discussed.

PMID- 8530419
TI  - Suppression of gene expression on the simian virus 40 major late promoter by
      human TR4 orphan receptor. A member of the steroid receptor superfamily.
AB  - The key expression of the simian virus 40 (SV40) major late promoter could be
      repressed by the human TR4 orphan receptor via the +55 region of the SV40 major
      late promoter (nucleotide numbers 368-389, 5' -GTTA-AGGTTCGTAGGTCATGGA-3'). Using
      the coupled in vitro transcribed and translated TR4 orphan receptor with a
      molecular mass of 67.3 kilodaltons, electrophoretic mobility shift assay showed
      specific binding with a dissociation constant of 1.09 nM between the TR4 orphan
      receptor and the SV40 +55 oligonucleotides. In addition, chloramphenicol
      acetyltransferase assay demonstrated that this SV40 +55 region can function as a
      repressor via the TR4 orphan receptor, suppressing the transcriptional activities
      of both SV40 early and late promoters. Together, our data suggest that the TR4
      orphan receptor may play an important role for the suppression of the SV40 gene
      expression.

PMID- 8530418
TI  - Multiple functions of the TR2-11 orphan receptor in modulating activation of two
      key cis-acting elements involved in the retinoic acid signal transduction system.
AB  - The testicular receptor 2 (TR2) orphan receptor binds to hormone response
      elements (HREs) consisting of two AGGTCA half-site direct repeat consensus
      sequences (DR) with various spacing in the following order: DR1 > DR2 > DR5 DR4
      DR6 > DR3. When binding to natural HREs, TR2 orphan receptor remains flexible
      with higher binding affinities to (a) cellular retinol-binding protein II
      promoter region (CRBPIIp) (DR1), SV40 +55 region (DR2), and retinoic acid
      response element beta (RARE beta) (DR5) than to (b) NGFI-B response element
      (NBRE) and also to (c) the palindromic thyroid hormone response element (TREpal).
      This wide spectrum of HRE recognition sequences suggests possible versatility of
      the TR2 orphan receptor in cross-talking with other signal transduction systems.
      Chloramphenicol acetyltransferase (CAT) assay demonstrates that the TR2 orphan
      receptor competes with CRBPIIp- and RARE beta-CAT gene expression activated by
      retinoid X receptor alpha (RXR alpha) and retinoic acid receptor alpha (RAR
      alpha)/RXR alpha heterodimers, respectively. In addition, this suppression may
      not be mediated by the formation of heterodimers between TR2 orphan receptor and
      either RXR alpha or RAR alpha. Instead, a minimum of 100-fold higher affinity of
      the TR2 orphan receptor for CRBPIIp than RXR alpha may explain why the TR2 orphan
      receptor dominates RXR alpha in CRBPIIp-CAT activation. Together, our data
      suggest that the TR2 orphan receptor may be a master regulator in modulating the
      activation of two key HREs, RARE beta and CRBPIIp, involved in the retinoic acid
      signal transduction pathway.

PMID- 8530420
TI  - Overexpression of epsilon-protein kinase C enhances nerve growth factor-induced
      phosphorylation of mitogen-activated protein kinases and neurite outgrowth.
AB  - Protein kinase C (PKC) activation enhances neurite outgrowth in several cell
      lines and primary neurons. The PKC isozymes that mediate this response are
      unknown. One clue to their identity has come from studies using PC12 cells
      treated with ethanol. In these cells, ethanol increases levels of delta-PKC and
      epsilon-PKC and markedly enhances nerve growth factor (NGF)-induced neurite
      outgrowth and activation of mitogen-activated protein (MAP) kinases by a PKC
      dependent mechanism. Since these findings suggest that delta-PKC or epsilon-PKC
      can promote neural differentiation, we studied neurite outgrowth in stably
      transfected PC12 cell lines that overexpress these isozymes. Overexpression of
      epsilon-PKC markedly increased NGF-induced neurite outgrowth. This effect was
      blocked by down-regulating PKC or by treating cells with the PKC inhibitor GF
      109203X. In addition, overexpression of epsilon-PKC enhanced NGF-induced
      phosphorylation of MAP kinases. In contrast, overexpression of delta-PKC did not
      alter responses to NGF. These results demonstrate that epsilon-PKC promotes NGF
      induced neurite outgrowth by enhancing NGF signal transduction. These findings
      suggest a role for epsilon-PKC in neural differentiation and plasticity.

PMID- 8530421
TI  - The nuclear-encoded chlorophyll-binding photosystem II-S protein is stable in the
      absence of pigments.
AB  - The 22-kDa chlorophyll a/b-binding protein (CAB) (psbS gene product) is
      associated with photosystem II and related to the CAB gene family. Here we report
      that the PSII-S protein unlike other chlorophyll-binding proteins is stable in
      the absence of pigments. It is present in etiolated spinach plants and
      accumulates in the dark progressively with the cellular development of the
      seedlings. Furthermore, it is present in several pigment-deficient mutants.
      Analysis of the pigment composition of the PSII-S protein isolated from etiolated
      plants suggests that neither carotenoids nor chlorophyll precursors are involved
      in its stabilization in the dark. Exposure of etiolated spinach to light leads to
      further accumulation of the PSII-S protein, which appears more early than other
      chlorophyll-binding proteins. Accumulation of the PSII-S protein in green plants
      is developmentally regulated and restricted to photosynthetic tissues. It is
      suggested that the function of the PSII-S protein may not be light-harvesting but
      it could act as a ligand chaperone required for transient binding of pigments
      during biogenesis or turnover of chlorophyll-binding proteins. Such function
      would be essential for coordination between pigment biosynthesis and ligation as
      well as avoiding toxic effects of non-bound chlorophyll molecules.

PMID- 8530422
TI  - Multiple regions of yeast ribosomal protein L1 are important for its interaction
      with 5 S rRNA and assembly into ribosomes.
AB  - Yeast ribosomal protein L1 binds to 5 S rRNA and can be released from 60 S
      ribosomal subunits as an intact ribonucleoprotein particle. To identify residues
      important for binding of Saccharomyces cerevisiae rpL1 to 5 S rRNA and assembly
      into functional ribosomes, we have isolated mutant alleles of the yeast RPL1 gene
      by site-directed and random mutagenesis. The rpl1 mutants were assayed for
      association of rpL1 with 5 S rRNA in vivo and in vitro and assembly of rpL1 into
      functional 60 S ribosomal subunits. Consistent with previous data implicating the
      importance of the carboxyl-terminal 47 amino acids of rpL1 for binding to 5 S
      rRNA in vitro, we find that deletion of the carboxyl-terminal 8, 25, or 44 amino
      acids of rpL1 confers lethality in vivo. Missense mutations elsewhere in rpL1
      also affect its function, indicating that multiple regions of rpL1 are important
      for its association with 5 S rRNA and assembly into ribosomes.

PMID- 8530423
TI  - A second osmosensing signal transduction pathway in yeast. Hypotonic shock
      activates the PKC1 protein kinase-regulated cell integrity pathway.
AB  - Yeast cells respond to hypertonic shock by activation of a (MAP) mitogen
      activated protein kinase cascade called the (HOG) high osmolarity glycerol
      response pathway. How yeast respond to hypotonic shock is unknown. Results of
      this investigation show that a second MAP kinase cascade in yeast called the
      protein kinase C1 (PKC1) pathway is activated by hypotonic shock. Tyrosine
      phosphorylation of the PKC1 pathway MAP kinase increased rapidly in cells
      following a shift of the external medium to lower osmolarity. The intensity of
      the response was proportional to the magnitude of the decrease in extracellular
      osmolarity. This response to hypotonic shock required upstream protein kinases of
      the PKC1 pathway. Increasing external osmolarity inhibited tyrosine
      phosphorylation of the PKC1 pathway MAP kinase, a response that was blocked by
      BCK1-20, a constitutively active mutant in an upstream protein kinase. These
      results indicate that yeast contain two osmosensing signal transduction pathways,
      the HOG pathway and the PKC1 pathway, that respond to hypertonic and hypotonic
      shock, respectively.

PMID- 8530424
TI  - The TATA-less promoter of mouse ribonucleotide reductase R1 gene contains a TFII
      I binding initiator element essential for cell cycle-regulated transcription.
AB  - Mammalian ribonucleotide reductase shows S-phase specific expression and consists
      of two non-identical subunits, proteins R1 (large subunit) and R2 (small
      subunit). A comparison between the human and mouse TATA-less R1 gene promoters
      revealed four highly conserved DNA regions, while the remaining sequence showed a
      low degree of conservation. Two regions, alpha and beta, were earlier identified
      as protein binding regions in the mouse R1 promoter by using DNase footprinting
      technique. The two new regions are located to the transcription start and to a
      DNA sequence about 40 base pairs downstream from the start. Gel shift assays
      using TFII-I antibodies and competition with an oligonucleotide representing the
      terminal deoxynucleotidyl transferase inhibitor element identified the start
      region as a TFII-I binding initiator element. The conserved downstream region,
      called gamma, also formed specific DNA-protein complexes in gel shift assays.
      Functional studies, using synchronized cells stably transformed by R1 promoter
      luciferase reporter gene constructs, indicated that the initiator and the gamma
      elements together were necessary for cell cycle-regulated R1 promoter activity.
      Earlier published data, indicating Sp1 binding to the R1 alpha/beta regions,
      could not be confirmed, suggesting that the R1 initiator element may function
      independent of Sp1.

PMID- 8530425
TI  - Stimulation of the herpes simplex virus type I protease by antichaeotrophic
      salts.
AB  - The herpes simplex virus type 1 protease is expressed as an 80,000-dalton
      polypeptide, encoded within the 635-amino acid open reading frame of the UL26
      gene. The two known protein substrates for this enzyme are the protease itself
      and the capsid assembly protein ICP35 (Liu, F., and Roizman, B. (1991) J. Virol.
      65, 5149-5156). In this report we describe the use of a rapid and quantitative
      assay for characterizing the protease. The assay uses a glutathione S-transferase
      fusion protein containing the COOH-terminal cleavage site of ICP35 as the
      substrate (GST-56). The protease consists of N0, the NH2-terminal 247 amino acid
      catalytic domain of the UL26 gene product, also expressed as a GST fusion
      protein. Upon cleavage with N0, a single 25-mer peptide is released from GST-56,
      which is soluble in trichloroacetic acid. Using this assay, the protease
      displayed a pH optimum between 7 and 9 but most importantly had an absolute
      requirement for high concentrations of an antichaeotrophic agent. Strong salting
      out salts such as Na2SO4 and KPO4 (> or = 1 M) stimulated activity, whereas NaCl
      and KCl had no effect. The degree of stimulation by 1.25 M Na2SO4 and KPO4 were
      100-150- and 200-300-fold, respectively. Using the fluorescent probe 1-anilino-8
      naphthalene sulfonate, the protease was shown to bind the dye in the presence of
      1.25 M Na2SO4 or KPO4, but not at low ionic strength or in the presence of 1.25
      or 2.2 M NaCl. This binding was most likely at the protease active site because a
      high affinity cleavage site peptide, but not a control peptide, could displace
      the dye. In addition to cleaving GST-56, the herpes simplex virus type I protease
      also cleaved the purified 56-mer peptide. Circular dichroism and NMR spectroscopy
      showed the peptide to be primarily random coil under physiological conditions,
      suggesting that antichaeotrophic agents affect the conformation of the substrate
      as well as the protease.

PMID- 8530426
TI  - 7-O-acetyl-GD3 in human T-lymphocytes is detected by a specific T-cell-activating
      monoclonal antibody.
AB  - The monoclonal antibody U5, which is a potent inducer of proliferation in human T
      cells, was found to bind to an alkali-sensitive derivative of ganglioside GD3.
      Using immunochemical and spectroscopic methods, the structure of the U5 antigen
      was determined as 7-O-acetyl-GD3. The antibody U5 did not react with 9-O-acetyl
      GD3 and bound severalfold more stronger to 7-O-acetyl-GD3 than to GD3. U5 is the
      first antibody known to detect preferentially 7-O-acetyl-GD3. Flow cytometric
      analysis showed that each major class of human leukocytes contained a significant
      fraction of cells binding the U5 antibody.

PMID- 8530427
TI  - Role of the RCII-D1 protein in the reversible association of the oxygen-evolving
      complex proteins with the lumenal side of photosystem II.
AB  - The nuclear-encoded proteins of the oxygen-evolving complex (OEC) of photosystem
      II are bound on the lumenal side of the thylakoid membrane and stabilize the
      manganese ion cluster forming the photosystem II electron donor side. The OEC
      proteins are released from their binding site(s) following light-induced
      degradation of reaction center II (RCII)-D1 protein in Chlamydomonas reinhardtii.
      The kinetics of OEC proteins release correlates with that of RCII-D1 protein
      degradation. Only a limited amount of RCII-D2 protein is degraded during the
      process, and no loss of the core proteins CP43 and CP47 is detected. The release
      of the OEC proteins is prevented when the photoinactivated RCII-D1 protein
      degradation is retarded by addition of 3-(3,5-dichlorophenyl)-1,1-dimethylurea or
      by a high PQH2/PQ ratio prevailing in membranes of the plastocyanin-deficient
      mutant Ac208. The released proteins are not degraded but persist in the thylakoid
      lumen for up to 8 h and reassociate with photosystem II when new D1 protein is
      synthesized in cells exposed to low light, thus allowing recovery of photosystem
      II function. Reassociation also occurs following D1 protein synthesis in darkness
      when RCII activity is only partially recovered. These results indicate that (i)
      the D1 protein participates in the formation of the lumenal OEC proteins binding
      site(s) and (ii) the photoinactivation of RCII-D1 protein does not alter the
      conformation of the donor side of photosystem II required for the binding of the
      OEC proteins.

PMID- 8530429
TI  - Structure-specific nuclease activity in yeast nucleotide excision repair protein
      Rad2.
AB  - Saccharomyces cerevisiae Rad2 protein functions in the incision step of the
      nucleotide excision repair of DNA damaged by ultraviolet light. Rad2 was
      previously shown to act endonucleolytically on circular single-stranded M13 DNA
      and also to have a 5'-->3' exonuclease activity (Habraken, Y., Sung, P., Prakash,
      L., and Prakash, S. (1993) Nature 366, 365-368; Habraken, Y., Sung, P., Prakash,
      L., and Prakash, S. (1994) J. Biol. Chem. 269, 31342-31345). Using two different
      branched DNA structures, pseudo Y and flap, we have determined that Rad2
      specifically cleaves the 5'-overhanging single strand in these DNAs. Rad2
      nuclease is more active on the flap structure than on the pseudo Y structure.
      Rad2 also acts on a bubble structure that contains an unpaired region of 14
      nucleotides, but with a lower efficiency than on the pseudo Y or flap structure.
      The incision points occur at and around the single strand-duplex junction in the
      three classes of DNA structures.

PMID- 8530428
TI  - Cross-linking and fluorescence study of the COOH- and NH2-terminal domains of
      intact caldesmon bound to actin.
AB  - The NH2- and COOH-terminal domains of muscle caldesmon are separated by a long
      alpha-helical stretch. Cys-580, in the COOH-terminal domain, can be rapidly and
      efficiently disulfide-cross-linked to Cys-374 of actin by incubation with actin
      modified with 5,5'-dithiobis(2-nitrobenzoic acid) (Graceffa, P., and Jancso, A.
      (1991) J. Biol. Chem. 266, 20305-20310). Upon further incubation (+/-
      tropomyosin), a second cross-link was slowly formed between Cys-153 in the NH2
      terminal domain and Cys-374 of another actin monomer. The yield of the second
      cross-link was relatively insensitive to increasing ionic strength, whereas the
      caldesmon-actin binding strength decreased considerably, suggesting that the NH2
      terminal domain is largely dissociated from actin and becomes slowly cross-linked
      to it during collisions with the actin filament. In support of these conclusions,
      the yield of photocross-linking actin to caldesmon specifically labeled with
      benzophenonemaleimide at Cys-580 was high, but close to zero for caldesmon
      labeled at Cys-153, and the fluorescence intensity and polarization of
      tetramethylrhodamine iodoacetamide attached to Cys-580 showed large changes,
      while there were no changes for the probe at Cys-153 upon binding caldesmon to
      actin (+/- tropomyosin). These findings are consistent with the knowledge that
      COOH-terminal fragments of caldesmon bind to actin, whereas NH2-terminal
      fragments do not. Since the NH2-terminal domain of caldesmon binds to myosin, a
      dissociated NH2-terminal domain may account for caldesmon's ability to link
      myosin and actin filaments.

PMID- 8530430
TI  - The effects of brefeldin A on the glucose transport system in rat adipocytes.
      Implications regarding the intracellular locus of insulin-sensitive Glut4.
AB  - Insulin activates glucose transport by recruiting Glut4 glucose transporters from
      an intracellular pool to plasma membrane (PM). To localize intracellular
      translocating Glut4, we studied the effects of brefeldin A (BFA), which
      disassembles Golgi and prevents trans-Golgi vesicular budding, on the glucose
      transport system. Isolated rat adipocytes were treated with and without both BFA
      (10 micrograms/ml) and insulin. BFA did not affect maximal rates of either 2
      deoxyglucose or 3-O-methyl-glucose transport or the insulin:glucose transport
      dose-response curve but did increase basal transport by approximately 2-fold (p <
      0.05). We also measured Glut4 in PM, low (LDM) and high density microsome
      subfractions. In basal cells, BFA increased PM Glut4 by 58% concomitant with a
      18% decrease in LDM (p < 0.05). Insulin alone increased PM Glut4 by 3-fold
      concomitant with a 56% decrease in LDM. BFA did not affect insulin-induced
      changes in Glut4 levels in PM or LDM. Most intracellular Glut4 was localized to
      sub-PM vesicles by immunoelectron microscopy in basal cells, and BFA did not
      affect insulin-mediated recruitment of immunogold-labeled Glut4 to PM. In
      summary, 1) in basal cells, BFA led to a small increase in glucose transport
      activity and redistribution of a limited number of transporters from LDM to PM;
      2) BFA did not affect insulin's ability to stimulate glucose transport or recruit
      normal numbers of LDM Glut4 to PM; and 3) insulin action is predominantly
      mediated by a BFA-insensitive pool of intracellular Glut4, which localizes to sub
      PM vesicles. Thus, the major translocating pool of Glut4 in rat adipocytes does
      not involve trans-Golgi.

PMID- 8530431
TI  - Phosphorylation of tyrosine 537 on the human estrogen receptor is required for
      binding to an estrogen response element.
AB  - We report here that the phosphorylation of tyrosine 537 on the human estrogen
      receptor (hER) controls the receptor's dimerization and DNA binding ability. The
      DNA-binding form of both the hER from human MCF-7 mammary carcinoma cells and the
      hER overexpressed in Sf9 insect cells was isolated using estrogen response
      element (ERE) affinity chromatography. Western blot analyses demonstrated that
      the DNA-binding form of the hER from MCF-7 or Sf9 cells was (i) phosphorylated at
      tyrosine 537, (ii) localized in the nucleus of estradiol-treated MCF-7 cells with
      an apparent molecular mass of 67 kDa, and (iii) hyperphosphorylated at serine
      residue(s). The non-DNA-binding form of the hER was (i) devoid of phosphorylation
      at tyrosine 537, (ii) cytosolic with an apparent molecular mass of 66 kDa, and
      (iii) hypophosphorylated at serine residue(s). The dephosphorylation of the
      purified hER at phosphotyrosine 537 with a tyrosine phosphatase eliminated
      binding to an ERE in a gel mobility shift assay. The binding of the tyrosine
      dephosphorylated hER to an ERE was restored by the rephosphorylation of tyrosine
      537 with Src family tyrosine kinases, p60c-src or p56lck. Mutation of tyrosine
      537 to phenylalanine confirmed that the phosphorylation of tyrosine 537 is
      necessary for the hER to bind an ERE. An anti-hER antibody restored the binding
      of the tyrosine-dephosphorylated hER to an ERE, indicating that the bivalent anti
      hER antibody brought together the two inactive hER monomers. A far-Western blot
      confirmed that phosphotyrosine 537 is required for hER homodimerization. These
      experiments establish that dimerization of the hER and DNA binding are regulated
      by phosphorylation at tyrosine 537. This is the first demonstration of the
      regulation of dimerization of a steroid hormone receptor by phosphorylation.
      These results are significant since p60c-src is overexpressed in estrogen
      dependent breast cancers and may act to enhance the activity of the hER.

PMID- 8530432
TI  - Characterization of functional domains within the multifunctional transcription
      factor, YY1.
AB  - YY1 is a multifunctional transcription factor capable of either activation or
      repression of transcription. Using a series of mutant proteins, we have
      characterized domains responsible for activation or repression. We found that the
      YY1 transcriptional activation domain lies near the amino terminus and requires
      amino acids 16-29 and 80-100 for maximal activity. The region between residues 16
      and 29 has the potential to form an acidic amphipathic helix, whereas residues
      between 80 and 100 are rich in proline and glutamine. The YY1 repression domain
      lies near the carboxyl terminus and is embedded within the YY1 zinc finger region
      necessary for binding to DNA. Deletion of YY1 amino acids, which include zinc
      fingers 3 and 4, abolishes repression. However, site-directed mutagenesis,
      progressive deletion, and internal deletion mutant analyses indicate that the
      normal structures of zinc fingers 3 and 4 are not required for repression.

PMID- 8530433
TI  - Sulfated glycans stimulate endocytosis of the cellular isoform of the prion
      protein, PrPC, in cultured cells.
AB  - There is currently no effective therapy for human prion diseases. However,
      several polyanionic glycans, including pentosan sulfate and dextran sulfate,
      prolong the incubation time of scrapie in rodents, and inhibit the production of
      the scrapie isoform of the prion protein (PrPSc), the major component of
      infectious prions, in cultured neuroblastoma cells. We report here that pentosan
      sulfate and related compounds rapidly and dramatically reduce the amount of PrPC,
      the non-infectious precursor of PrPSc, present on the cell surface. This effect
      results primarily from the ability of these agents to stimulate endocytosis of
      PrPC, thereby causing a redistribution of the protein from the plasma membrane to
      the cell interior. Pentosan sulfate also causes a change in the ultrastructural
      localization of PrPC, such that a portion of the protein molecules are shifted
      into late endosomes and/or lysosomes. In addition, we demonstrate, using PrP
      containing bacterial fusion proteins, that cultured cells express saturable and
      specific surface binding sites for PrP, many of which are glycosaminoglycan
      molecules. Our results raise the possibility that sulfated glycans inhibit prion
      production by altering the cellular localization of PrPC precursor, and they
      indicate that endogenous proteoglycans are likely to play an important role in
      the cellular metabolism of both PrPC and PrPSc.

PMID- 8530435
TI  - Eosinophil cationic protein and eosinophil-derived neurotoxin. Evolution of novel
      function in a primate ribonuclease gene family.

PMID- 8530434
TI  - Photocross-links between single-stranded DNA and Escherichia coli RecA protein
      map to loops L1 (amino acid residues 157-164) and L2 (amino acid residues 195
      209).
AB  - To function as a repair and recombination protein, RecA has to be assembled as an
      active filament on single-stranded DNA in the presence of ATP or its analogs. We
      have identified amino acids in the primary DNA binding site of RecA that interact
      with single-stranded DNA by photocross-linking. A nucleoprotein complex
      consisting of RecA protein bound to a monosubstituted oligonucleotide bearing a 5
      iododeoxyuracil cross-linking moiety was irradiated with long wavelength
      ultraviolet radiation to effect cross-linking with RecA protein. Subsequent
      trypsin digestion, followed by purification and peptide sequencing, revealed the
      cross-linking of two independent peptides, amino acid residues 153-169 and 199
      216. Met164 from loop L1 and Phe203 from loop L2 were determined to be the exact
      points of cross-linking. Thus, our data confirm and extend predictions about the
      DNA binding domain of RecA protein based on the molecular structure of RecA
      (Story, R. M., Weber, I. T., and Steitz, T. A. (1992) Nature 355, 318-325).

PMID- 8530436
TI  - Mechanisms of intron mobility.

PMID- 8530437
TI  - Interactions between the protein-tyrosine kinase ZAP-70, the proto-oncoprotein
      Vav, and tubulin in Jurkat T cells.
AB  - Two molecules involved in signal transduction via the T cell antigen receptor,
      namely the protein-tyrosine kinase ZAP-70 and the proto-oncoprotein Vav, were
      found to be constitutively associated with tubulin in Jurkat T cells. Both were
      able to bind to tubulin independently of one another, as determined by transient
      transfection into COS-7 cells. The ZAP-70 associated with tubulin was
      preferentially tyrosine-phosphorylated after T cell antigen receptor stimulation
      of Jurkat T cells, suggesting that this interaction was functionally significant.
      Vav was also found to co-immunoprecipitate with ZAP-70 from cell extracts
      depleted of tubulin. This raised the possibility that Vav might be a substrate
      for ZAP-70 protein-tyrosine kinase activity. However, tyrosine phosphorylation of
      Vav preceded that of ZAP-70, indicating that Vav was unlikely to be a downstream
      target of ZAP-70. The association of ZAP-70 and Vav with tubulin implies that the
      microtubules may be involved in the signaling function of these two molecules,
      perhaps by targeting them to their appropriate intracellular location.

PMID- 8530438
TI  - Functional elimination of calmodulin within the nucleus by targeted expression of
      an inhibitor peptide.
AB  - Genetic manipulation has proven valuable in identifying the role of specific
      genes in cellular function. Genomic disruption of genes that are expressed during
      embryonic development or in multiple tissue types, however, complicates
      phenotypic analysis. We demonstrate that targeted expression of an inhibitor
      peptide derived from myosin light chain kinase can neutralize the function of
      calmodulin. We have shown that elimination of the nuclear function of Ca(2+)
      calmodulin causes disruption of the nuclear structure. Targeted expression of
      this calmodulin inhibitor gene in the lung epithelium of transgenic mice leads to
      cellular death and dysfunctional lung development. This approach is a strategy to
      modify the activity of a targeted protein within a specific organelle in order to
      evaluate its role in cellular and tissue function.

PMID- 8530439
TI  - A conserved downstream element defines a new class of RNA polymerase II
      promoters.
AB  - Although many TATA-less promoters transcribed by RNA polymerase II initiate
      transcription at multiple sites, the regulation of multiple start site
      utilization is not understood. Beginning with the prediction that multiple start
      site promoters may share regulatory features and using the P-glycoprotein
      promoter (which can utilize either a single or multiple transcription start
      site(s)) as a model, several promoters with analogous transcription windows were
      grouped and searched for the presence of a common DNA element. A downstream
      protein-binding sequence, MED-1 (Multiple start site Element Downstream), was
      found in the majority of promoters analyzed. Mutation of this element within the
      P-glycoprotein promoter reduced transcription by selectively decreasing
      utilization of downstream start sites. We propose that a new class of RNA
      polymerase II promoters, those that can utilize a distinctive window of multiple
      start sites, is defined by the presence of a downstream MED-1 element.

PMID- 8530440
TI  - Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes
      mellitus due to defective insulin secretion to glucose.
AB  - Mice carrying a null mutation in the glucokinase (GK) gene in pancreatic beta
      cells, but not in the liver, were generated by disrupting the beta-cell-specific
      exon. Heterozygous mutant mice showed early-onset mild diabetes due to impaired
      insulin-secretory response to glucose. Homozygotes showed severe diabetes shortly
      after birth and died within a week. GK-deficient islets isolated from homozygotes
      showed defective insulin secretion in response to glucose, while they responded
      to other secretagogues: almost normally to arginine and to some extent to
      sulfonylureas. These data provide the first direct proof that GK serves as a
      glucose sensor molecule for insulin secretion and plays a pivotal role in glucose
      homeostasis. GK-deficient mice serve as an animal model of the insulin-secretory
      defect in human non-insulin-dependent diabetes mellitus.

PMID- 8530441
TI  - Requirement of calmodulin-dependent protein kinase II in cyclic ADP-ribose
      mediated intracellular Ca2+ mobilization.
AB  - Cyclic ADP-ribose (cADPR) is generated in pancreatic islets by glucose
      stimulation, serving as a second messenger for Ca2+ mobilization from the
      endoplasmic reticulum for insulin secretion (Takasawa, S., Nata, K., Yonekura,
      H., and Okamoto, H. (1993) Science 259, 370-373). In the present study, we
      observed that the addition of calmodulin (CaM) to rat islet microsomes sensitized
      and activated the cADPR-mediated Ca2+ release. Inhibitors for CaM-dependent
      protein kinase II (CaM kinase II) completely abolished the glucose-induced
      insulin secretion as well as the cADPR-mediated and CaM-activated Ca2+
      mobilization. Western blot analysis revealed that the microsomes contain the
      alpha isoform of CaM kinase II but do not contain CaM. When the active 30-kDa
      chymotryptic fragment of CaM kinase II was added to the microsomes, fully
      activated cADPR-mediated Ca2+ release was observed in the absence of CaM. These
      results along with available evidence strongly suggest that CaM kinase II is
      required to phosphorylate and activate the ryanodine-like receptor, a Ca2+
      channel for cADPR as an endogenous activator, for the cADPR-mediated Ca2+
      release.

PMID- 8530442
TI  - Chimeric substitutions of the actin-binding loop activate dephosphorylated but
      not phosphorylated smooth muscle heavy meromyosin.
AB  - Regulatory light chain (RLC) phosphorylation is necessary to activate smooth
      muscle myosin, unlike constitutively active striated muscle myosins. Here we show
      that an actin-binding surface loop located at the 50/20-kDa junction contributes
      to this fundamental difference between myosins. Substitution of the native actin
      binding loop of smooth muscle heavy meromyosin (HMM) with that from either
      skeletal or beta-cardiac myosin caused the chimeric HMMs to become unregulated
      like the myosin from which the loop was derived. Dephosphorylated chimeric HMMs
      gained the ability to move actin in a motility assay and had 50-70% of the actin
      activated ATPase activity of phosphorylated wild-type HMM. Direct binding
      measurements showed that the affinity of HMM for actin in the presence of MgATP
      was unaffected by loop substitution; thus the rate of a step other than binding
      is increased. Phosphorylation of the chimeras did not lead to a higher Vmax than
      obtained for wild-type HMM. In the absence of actin, a foreign loop did not
      affect nucleotide trapping. Native regulated molecules have thus evolved a loop
      sequence which prevents rapid product release by actin when the RLC is
      dephosphorylated, thereby allowing activity to be controlled by RLC
      phosphorylation.

PMID- 8530443
TI  - Stat1 depends on transcriptional synergy with Sp1.
AB  - STAT (signal transducer and activator of transcription) proteins combine with
      cytokine receptors and receptor-associated kinases in distinct protein/protein
      interactions that are critical for STAT-dependent signal transduction events, but
      the nature of any subsequent STAT interactions with DNA-binding proteins in the
      nucleus is less certain. Based on assays of DNA/protein binding and activity of
      transfected reporter plasmids, we determined that occupation of contiguous DNA
      binding sites for Stat1 (the first member of the STAT family) and the
      transcriptional activator Sp1 are both required for full activation of the
      intercellular adhesion molecule-1 gene by interferon-gamma. Thus, Stat1 binding
      to DNA cannot by itself be equated with biologic actions of Stat1. In co
      immunoprecipitation experiments, we also obtained evidence of direct and
      selective Stat1/Sp1 interaction (in primary culture cells without
      overexpression), further indicating that Stat1/Sp1 synergy confers an element of
      specificity in the pathway leading to cytokine-activated transcription and
      cytokine-dependent immunity and inflammation.

PMID- 8530444
TI  - The C-terminal sequence of the chaperonin GroES is required for oligomerization.
AB  - The Escherichia coli protein GroES is a co-chaperonin that is able to assist
      GroEL in the refolding of proteins. GroES is a heptamer of seven identical
      subunits. Recent work has focused on the structural aspects of GroES. We have
      investigated the role of the C-terminal portion of GroES on its oligomerization.
      Limited proteolysis of GroES by carboxypeptidase Y gives a product in which the C
      terminal 7 amino acid residues have been removed. Sedimentation velocity analysis
      reveals that the truncated form of GroES is unable to reassemble. The results
      presented here implicate the C-terminal sequence in intermonomer actions within
      the GroES oligomer. In addition, this work provides experimental verification of
      predictions implied in the recent x-ray determination of the GroES structure
      (Hunt, J. F., Weaver, A. J., Landry, S. J., Gierasch, L. M., and Deisenhofer, J.
      Nature, in press).

PMID- 8530446
TI  - Cysteine-rich region of Raf-1 interacts with activator domain of post
      translationally modified Ha-Ras.
AB  - The interaction between "switch I/effector domain" of Ha-Ras and the Ras-binding
      domain (RBD, amino acid 51-131) of Raf-1 is essential for signal transduction.
      However, the importance of the "activator domain" (approximately corresponding to
      amino acids 26-28 and 40-49) of Ha-Ras and of the "cysteine-rich region" (CRR,
      amino acids 152-184) of Raf-1 have also been proposed. Here, we found that Raf-1
      CRR interacts directly with Ha-Ras independently of RBD and that participation of
      CRR is necessary for efficient Ras-Raf binding. Furthermore, Ha-Ras carrying
      mutations (N26G and V45E) in the activator domain failed to bind CRR, whereas
      they bound RBD normally. On the contrary, Ha-Ras carrying mutations in the switch
      I/effector domain exhibited severely reduced ability to bind RBD, whereas their
      ability to bind CRR was unaffected. Mutants that bound to either RBD or CRR alone
      failed to activate Raf-1. Ha-Ras without post-translational modifications, which
      lacks the ability to activate Raf-1, selectively lost the ability to bind CRR.
      These results suggest that the activator domain of Ha-Ras participates in
      activation of Raf-1 through interaction with CRR and that post-translational
      modifications of Ha-Ras are required for this interaction.

PMID- 8530445
TI  - Granulocyte-macrophage colony-stimulating factor induces the transcriptional
      activation of egr-1 through a protein kinase A-independent signaling pathway.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) rapidly and transiently
      induces the transcriptional activation of the early growth response gene-1 (egr
      1) in the human factor-dependent myeloid leukemic cell line, TF-1. We previously
      demonstrated that the cAMP response element (CRE) is required for GM-CSF-induced
      egr-1 expression and that phosphorylation of CREB on serine 133 plays a critical
      role during GM-CSF signal transduction. To determine whether GM-CSF activates
      signaling pathways through a protein kinase A-dependent or -independent pathway,
      we measured cAMP levels following GM-CSF or forskolin treatment of TF-1 cells.
      Forskolin but not GM-CSF stimulation resulted in an increase in cAMP levels.
      Transient transfection assays with TF-1 cells were also performed with a -116
      nucleotide egr-1 promoter construct and the protein kinase inhibitor, PKI.
      Although PKI inhibited forskolin induction of the -116-nucleotide construct, it
      did not affect GM-CSF stimulation of this construct. In the present study, we
      demonstrated that GM-CSF induces egr-1 expression through a protein kinase A
      independent pathway.

PMID- 8530447
TI  - c-Abl activation regulates induction of the SEK1/stress-activated protein kinase
      pathway in the cellular response to 1-beta-D-arabinofuranosylcytosine.
AB  - Previous work has shown that treatment of cells with the antimetabolite 1-beta-D
      arabinofuranosylcytosine (ara-C) is associated with induction of the c-jun gene.
      The present studies demonstrate that ara-C activates the c-Abl non-receptor
      tyrosine kinase. We also demonstrate that activity of the stress-activated
      protein kinase (SAP kinase/JNK) is increased in ara-C-treated cells. Using cells
      deficient in c-Abl (Abl-/-) and after introduction of the c-abl gene, we show
      that ara-C-induced c-Abl activity is necessary for the stimulation of SAP kinase.
      Other studies using cells transfected with a SEK1 dominant negative demonstrate
      that ara-C-induced SAP kinase activity is SEK1-dependent. Furthermore, we show
      that overexpression of truncated c-Abl results in activation of the SEK1/SAP
      kinase cascade.

PMID- 8530448
TI  - Urokinase-type plasminogen activator-induced monocyte adhesion requires a
      carboxyl-terminal lysine and cAMP-dependent signal transduction.
AB  - Urokinase-type plasminogen activator (u-PA) or its amino-terminal fragment (ATF)
      containing the u-PA receptor (u-PAR) binding domain, is known to promote monocyte
      adhesion. In the present study, U937 monocyte adhesion to a plastic surface was
      used to investigate the mechanism of its promotion by u-PA and ATF. Adhesion was
      found to be inhibited by cycloheximide or actinomycin D, implicating protein
      synthesis and gene expression in u-PA-induced monocyte adhesion. Adhesion was
      prevented by 2'-deoxyadenosine 3'-monophosphate, indicating that a cAMP-dependent
      pathway of signal transduction was involved. This concept was supported by the
      complementary finding that u-PA-induced adhesion was greatly promoted by
      forskolin, cholera toxin, or 8-bromo-cAMP, which by themselves induced little
      adhesion. Furthermore, similar to many other cAMP-dependent activities, cGMP
      diminished u-PA-induced adhesion. When u-PA or ATF was treated with immobilized
      carboxypeptidase B, its proadhesive effect was abolished, implicating the
      involvement of carboxyl-terminal lysine residues (Lys158 on u-PA and Lys135 on
      ATF). Moreover, when a carboxyl-terminal lysine analog was added, the proadhesive
      effect of carboxypeptidase B-treated u-PA or ATF was restored. In conclusion, the
      present study indicates that u-PA- or ATF-induced monocyte adhesion involves cAMP
      dependent signal transduction, which is triggered by u-PAR binding. It is also
      critically dependent on the presence of a carboxyl-terminal lysine.

PMID- 8530449
TI  - Glucose modulates gamma-aminobutyric acid release from the pancreatic beta TC6
      cell line.
AB  - To determine if endogenous gamma-aminobutyric acid (GABA) is secreted by a
      pancreatic beta-cell-derived cell line and to determine the effects of glucose on
      GABA release, beta TC6 cultures were incubated in the presence of 1 or 10 mmol/l
      glucose for 12 h and then subjected to a 2-h secretion test in Krebs-Ringer
      buffer containing 1 or 10 mmol/l glucose. beta TC6-conditioned medium was
      collected at 15, 30, 60, and 120 min after glucose stimulation for GABA analysis
      by high pressure liquid chromatography-electrochemical detection. After 30 min,
      medium GABA concentrations were significantly higher (p < 0.05) in cultures that
      were exposed to high glucose during both the 12-h incubation period and the 2-h
      secretion test than in the remaining three glucose combinations. To address
      possible roles of beta-cell-derived GABA, the effect of GABA on glucagon
      secretion from pancreatic alpha TC6 cells was tested at concentrations released
      from beta TC6 cells. Inhibition of glucagon secretion by alpha TC6 cells was
      observed in the presence of GABA at concentrations equivalent to concentrations
      secreted by beta TC6 cells. The inhibitory effects of GABA on glucagon secretion
      by alpha TC6 cells were blocked by the GABAA receptor antagonist bicuculline and
      were dissociated from the inhibitory effects of glucose. Together, these results
      provide the first documentation that endogenous GABA is released from a highly
      differentiated beta-cell line and that glucose and GABA independently attenuate
      glucagon secretion by a pancreatic alpha-cell line.

PMID- 8530450
TI  - Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric
      oxide production and vasodilation.
AB  - Initial confinement of opiate receptors to the nervous system has recently been
      broadened to several other cell types. Based on the well established hypotensive
      effect of morphine, we hypothesized that endothelial cells may represent a target
      for this opiate substance. Endothelial cells (human arterial and rat
      microvascular) contain a high affinity, saturable opiate binding site presumed to
      mediate the morphine effects that is stereoselectively and characteristically
      antagonized by naloxone. This opiate alkaloid-specific binding site is
      insensitive to opioid peptides. It is, therefore, considered to be the same
      subtype of opiate receptor (designated mu3) used in the mediation of morphine in
      other cell types exhibiting the same binding profile. Experiments with
      endothelial cultures and the aortic ring of rats cultured in vitro demonstrate
      that morphine exerts direct modulatory control over the activities of endothelial
      cells, which leads to vasodilation. It induces the production of nitric oxide, a
      process that is sensitive to naloxone antagonism and nitric oxide synthase
      inhibition. In contrast with that of opiates, the administration of opioid
      peptides does not induce nitric oxide production by endothelial cells. In
      conclusion, the data presented above reveal a novel site of morphine action,
      endothelial cells, where a mu3 receptor is coupled to nitric oxide release and
      vasodilation.

PMID- 8530451
TI  - LEC18, a dominant Chinese hamster ovary glycosylation mutant synthesizes N-linked
      carbohydrates with a novel core structure.
AB  - The dominant Chinese hamster ovary cell glycosylation mutant, LEC18, was selected
      for resistance to pea lectin (Pisum sativum agglutinin (PSA)). Lectin binding
      studies show that LEC18 cells express altered cell surface carbohydrates with
      markedly reduced binding to 125I-PSA and increased binding to 125I-labeled Datura
      stramonium agglutinin (DSA) compared with parental cells. Desialylated [3H]Glc
      labeled LEC18 cellular glycopeptides that did not bind to concanavalin A
      Sepharose exhibited an increased proportion of species that were bound to DSA
      agarose. Most of these glycopeptides bound to ricin-agarose and were unique to
      LEC18 cells. This fraction was purified from approximately 10(10) cells and shown
      by 1H NMR spectroscopy and methylation linkage analysis to contain novel N-linked
      structures. Digestion of these glycopeptides with mixtures of beta-D
      galactosidases and N-acetyl-beta-D-glucosaminidases gave core glycopeptides that,
      in contrast to cores from parental cells, were mainly not bound to concanavalin A
      Sepharose or to PSA-agarose. 1H NMR spectroscopy, matrix-assisted laser
      desorption ionization/time of flight mass spectrometry, electrospray mass
      spectrometry, and collision-activated dissociation mass spectrometry showed that
      the LEC18 core glycopeptides contained a new GlcNAc residue that substitutes the
      core GlcNAc residues. Methylation linkage analysis of the parent compound
      provided evidence that the GlcNAc is linked at O-6 to give the following novel, N
      linked core structure. [formula: see text]

PMID- 8530452
TI  - C-jun and Egr-1 participate in DNA synthesis and cell survival in response to
      ionizing radiation exposure.
AB  - Exposure of mammalian cells to ionizing radiation results in the induction of the
      immediate early genes, c-jun and Egr-1, which encode transcription factors
      implicated in cell growth as well as the cellular response to oxidative stress.
      We studied the role of these immediate early genes in cell cycle kinetics and
      cell survival following x-irradiation of clones containing inducible dominant
      negatives to c-jun and Egr-1. The dominant negative constructs to c-jun (delta 9)
      and Egr-1 (WT/Egr) prevented x-ray induction of transcription through the AP-1
      and Egr binding sites, respectively. Twenty percent of confluent, serum-deprived
      SQ20B human tumor cells, normal fibroblasts, and fibroblasts from patients with
      ataxia telangiectasia entered S phase within 5 h of irradiation. Clones
      containing inducible delta 9 and WT/Egr dominant negative constructs demonstrated
      attenuation of the percentage of cells exiting G1 phase and reduced survival
      following irradiation. These data indicate that the dominant negatives to the
      stress-inducible immediate early genes Egr-1 and c-jun prevent the onset of S
      phase and reduce the survival of human cells exposed to ionizing radiation.

PMID- 8530453
TI  - Exchanging the extracellular domain of amyloid precursor protein for horseradish
      peroxidase does not interfere with alpha-secretase cleavage of the beta-amyloid
      region, but randomizes secretion in Madin-Darby canine kidney cells.
AB  - Secretory processing and polarized sorting of horseradish peroxidase fused to the
      amyloid precursor protein transmembrane domain were compared with those of wild
      type amyloid precursor protein in COS and polarized Madin-Darby canine kidney
      (MDCK) cells. The cellular and secreted forms of the chimeric protein were
      enzymatically active in colorimetric and cytochemical assays after reconstitution
      with hemin and Ca2+. The peroxidase enzyme was secreted by a proteolytic process,
      similar to the parent amyloid precursor protein. In polarized MDCK cells, amyloid
      precursor protein was secreted exclusively in the basolateral compartment, while
      the peroxidase chimeric protein was secreted in both compartments. The
      basolateral sorting determinant for secretion must therefore be located in the
      extracellular domain of amyloid precursor protein. On the other hand, cell
      surface-associated peroxidase chimeric protein was similar to cell surface
      associated wild-type amyloid precursor protein, mainly expressed at the
      basolateral side. The basolateral cell-surface expression, in contrast to the
      basolateral secretion, is therefore controlled by determinants in the cytoplasmic
      domain. Methylamine inhibited and bafilomycin slightly increased the basolateral
      secretion of both proteins, but both drugs strongly increased apical secretion.
      The default secretory pathway of COS cells and the basolateral (but not the
      apical) secretory pathway of MDCK cells are therefore comparably sensitive to
      methylamine and not to bafilomycin.

PMID- 8530454
TI  - Molecular cloning and expression of serum calcium-decreasing factor (caldecrin).
AB  - We previously reported on the purification of a serum calcium-decreasing factor,
      referred to as caldecrin, from porcine pancreas, that is thought to be a serine
      protease (Tomomura, A., Fukushige, T., Noda, T., Noikura, T., and Saheki, T.
      (1992) FEBS Lett. 301, 277-281). In the present study, we purified caldecrin from
      rat pancreas and determined its primary structure by cDNA cloning. The predicted
      caldecrin protein is presumed to be synthesized as a preproenzyme of 268 amino
      acids with a signal peptide of 16 amino acids and an activation peptide of 13
      amino acids, and is, with the exception of a central region, almost identical to
      the reported rat pancreatic elastase IV sequence. The caldecrin gene is
      selectively expressed in the pancreas, as judged by Northern blot analysis. After
      expression in BMT-10 cells, immunoreactive caldecrin was found in the culture
      supernatant, and it inhibited the parathyroid hormone-stimulated 45Ca release
      from cultured fetal long bones. Catalytic site mutants were synthesized in a
      baculovirus system, and recombinant mutants also decreased the serum calcium
      level of mice. These data implicate caldecrin, a protease closely related to
      elastase IV, in the regulation of blood calcium levels.

PMID- 8530455
TI  - Analysis of elements in the substrate required for processing by mitochondrial
      processing peptidase.
AB  - We have recently demonstrated that synthetic peptides modeled on the extension
      peptide of malate dehydrogenase can be a good substrate of mitochondrial
      processing peptidase and that arginine residues present at positions -2 or -3 and
      distant from the cleavage point were important for recognition by the enzyme
      (Niidome, T., Kitada, S., Shimokata, K., Ogishima, T., and Ito, A. (1994) J.
      Biol. Chem. 269, 24719-24722). We further investigated the elements required for
      substrates of the protease. To analyze the reaction by a more rapid yet
      quantitative method, we have developed intramolecularly quenched fluorescent
      substrates. Using the fluorogenic substrates we demonstrated that at least one of
      the proline and glycine between the distal and proximal arginine residues was
      also important while other connecting sequences were dispensable. In addition,
      the protease showed considerable preference for aromatic and, to a lesser extent,
      hydrophobic amino acids in the P1'-position. These results together with the
      previous data suggest that the proximal and distal arginine residues, proline
      and/or glycine between them, and P1' amino acid could be critical determinants
      for the specific cleavage of the substrates by the protease.

PMID- 8530456
TI  - ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing
      metabolite from NADP.
AB  - ADP-ribosyl cyclase catalyzes the cyclization of NAD+ to produce cyclic ADP
      ribose (cADPR), which is emerging as an endogenous regulator of the Ca(2+)
      induced Ca2+ release mechanism in cells. CD38 is a lymphocyte differentiation
      antigen which has recently been shown to be a bifunctional enzyme that can
      synthesize cADPR from NAD+ as well as hydrolyze cADPR to ADP-ribose. In this
      study, we show that both the cyclase and CD38 can also catalyze the exchange of
      the nicotinamide group of NADP+ with nicotine acid (NA). The product is nicotinic
      acid adenine dinucleotide phosphate (NAADP+), a metabolite we have previously
      shown to be potent in Ca2+ mobilization (Lee, H. C., and Aarhus, R. (1995) J.
      Biol. Chem. 270, 2152-2157). The switch of the catalysis to the exchange reaction
      requires acidic pH and NA. The half-maximal effective concentration of NA is
      about 5 mM for both the cyclase and CD38. In the absence of NA or at neutral pH,
      the cyclase converts NADP+ to another metabolite, which is identified as cyclic
      ADP-ribose 2'-phosphate. Under the same conditions, CD38 converts NADP+ to ADP
      ribose 2'-phosphate instead, which is the hydrolysis product of cyclic ADP-ribose
      2'-phosphate. That two different products of ADP-ribosyl cyclase and CD38, cADPR
      and NAADP+, are both involved in Ca2+ mobilization suggests a crucial role of
      these enzymes in Ca2+ signaling.

PMID- 8530457
TI  - Activation of an H2O2-generating NADH oxidase in human lung fibroblasts by
      transforming growth factor beta 1.
AB  - The cellular source(s) and mechanisms of generation of reactive oxygen species
      (ROS) in nonphagocytic cells stimulated by cytokines are unclear. In this study,
      we demonstrate that transforming growth factor beta 1 (TGF-beta 1, 1 ng/ml)
      induces the release of H2O2 from human lung fibroblasts within 8 h following
      exposure to this cytokine. Elevation in H2O2 release peaked at 16 h
      (approximately 22 pmol/min/10(6) cells) and gradually declined to undetectable
      levels at 48 h after TGF-beta 1 treatment. NADH consumption by these cells was
      stimulated by TGF-beta 1 while that of NADPH remained unchanged. NADPH oxidase
      activity as measured by diphenyliodonium (DPI)-inhibitable NADH consumption in
      TGF-beta 1-treated cells followed a time course similar to that of H2O2 release.
      DPI, an inhibitor of the NADPH oxidase complex of neutrophils and other
      flavoproteins, also inhibited the TGF-beta 1-induced H2O2 production. Inhibitors
      of other enzymatic systems involving flavoproteins that may be responsible for
      the production of H2O2 in these cells, including xanthine oxidase, nitric oxide
      synthase, and both mitochondrial and microsomal electron transport systems,
      failed to inhibit TGF-beta 1-induced NADH oxidation and H2O2 production. The
      delay (> 4 h) following TGF-beta 1 exposure along with the inhibition of this
      process by cycloheximide and actinomycin D suggest the requirement of new protein
      synthesis for induction of NADH oxidase activity in TGF-beta 1-stimulated
      fibroblasts.

PMID- 8530458
TI  - Hormonal and nutritional control of the fatty acid synthase promoter in
      transgenic mice.
AB  - To study the molecular basis of tissue-specific and hormonally regulated
      expression of the fatty acid synthase (FAS) gene in vivo, we generated lines of
      transgenic mice carrying 2.1 kilobases of the 5'-flanking region (-2100 to +67)
      of the rat FAS gene fused to a chloramphenicol acetyltransferase (CAT) reporter
      gene. This reporter gene construct was strongly expressed in tissues that
      normally express high levels of FAS mRNA, which include liver and white adipose
      tissues. In contrast, CAT reporter activity was not detected in appreciable
      levels in lung, heart, kidney, and muscle tissues, which do not normally show
      significant levels of FAS activity. The relative levels of the CAT mRNA driven by
      the rat FAS promoter in various tissues of the transgenic animals approximated
      those of the endogenous mouse FAS mRNA. We also examined the hormonal and
      nutritional regulation of the FAS(2.1)-CAT reporter gene in transgenic mice. CAT
      activity was increased in both liver and white adipose tissue when fasted animals
      were refed a high carbohydrate, fat-free diet. These changes in CAT activity and
      CAT mRNA levels occurred in parallel to the changes in endogenous mouse FAS mRNA
      levels. On the other hand, fasting/refeeding did not change CAT activity
      appreciably in other tissues, such as muscle and brown adipose tissue.
      Administration of dibutyryl cAMP at the start of refeeding prevented an increase
      in CAT activity in liver. However, the cAMP effect was tissue-specific as cAMP
      treatment did not bring about change in CAT activity in adipose tissue. Next, to
      examine the effect of insulin, we made the transgenic mice insulin-deficient by
      streptozotocin treatment. Insulin treatment of the streptozotocin-diabetic mice
      increased both the CAT activity and CAT mRNA levels driven by the rat FAS
      promoter in liver and white adipose tissue. These changes in CAT expression by
      insulin paralleled those in endogenous FAS mRNA levels. Administration of
      glucocorticoids increased CAT activity in all tissues examined: liver, white and
      brown adipose tissues, lung, heart, and spleen. Overall, the first 2.1 kilobases
      of the 5'-flanking region of the rat FAS gene appear to contain sequence elements
      necessary to confer tissue-specific and hormonally regulated expression
      characteristic of the endogenous FAS gene.

PMID- 8530459
TI  - Cloning and expression of the mammalian cytosolic branched chain aminotransferase
      isoenzyme.
AB  - The cDNA for the rat cytosolic branched chain aminotransferase (BCATc) has been
      cloned. The BCATc cDNA encodes a polypeptide of 410 amino acids with a calculated
      molecular mass of 46.0 kDa. By Northern blot analysis, BCATc message of
      approximately 2.7 kilobases was readily detected in rat brain, but was absent
      from liver, a rat hepatoma cell line, kidney, and skeletal muscle. When expressed
      in COS-1 cells, the enzyme is immunologically indistinguishable from the native
      enzyme found in rat brain cytosol. Comparison of the rat BCATc sequence with
      available data bases identified the Escherichia coli (and Salmonella typhimurium)
      branched chain aminotransferase (BCAT) and revealed a Haemophilus influenzae
      BCAT, a yeast BCAT, which is hypothesized to be a mitochondrial form of the
      enzyme, and the murine BCATc (protein ECA39). Calculated molecular masses for the
      complete proteins are 33.9 kDa, 37.9 kDa, 42.9 kDa, and 43.6 kDa, respectively.
      The rat BCATc sequence was 84% identical with murine BCATc, 45% identical with
      yeast, 33% identical with H. influenzae, 27% identical with the E. coli and S.
      typhimurium BCAT, and 22% identical with the evolutionary related D-amino acid
      aminotransferase (D-AAT) (Tanizawa, K., Asano, S., Masu, Y., Kuramitsu, S.,
      Kagamiyama, H., Tanaka, H., and Soda, K. (1989) J. Biol. Chem. 264, 2450-2454).
      Amino acid sequence alignment of BCATc with D-AAT suggests that the folding
      pattern of the overlapping mammalian BCATc sequence is similar to that of D-AAT
      and indicates that orientation of the pyridoxal phosphate cofactor in the active
      site of the eukaryotic BCAT is the same as in D-AAT. Thus, BCAT are the only
      eukaryotic aminotransferases to abstract and replace the proton on the re face of
      the pyridoxal phosphate cofactor. Finally, requirements for recognition of
      substrate L-amino acid and alpha-carboxylate binding are discussed.

PMID- 8530460
TI  - Identification of metal-binding sites in rat brain calcium-binding protein.
AB  - Calbindin D28K binds 3 mol of terbium per mol of protein. To determine which of
      six EF-hand structures in the protein are responsible for terbium binding, we
      constructed three mutant forms of this protein, one lacking EF-hand 2 (RCaBP
      delta 2), the other lacking EF-hands 2 and 6 (RCaBP delta 2,6), and the third
      containing only EF-hands 3 and 4 (RCaBP delta 1,2,5,6), and examined their
      binding properties by fluorescence techniques. Full-length calbindin D28K and
      RCaBP delta 2 and RCaBP delta 2,6 bound 3 mol of terbium per mol of protein with
      high affinity. Thus, EF-hand domains 2 and 6 are not essential for calcium
      binding to the proteins, and an absence of EF-hands 2 and/or 6 does not alter the
      pattern of terbium binding to the protein. Using resonance energy transfer from
      tryptophan residues, one of the high affinity terbium-binding sites (site A) had
      a greater affinity than the other two sites (sites B and C) of each protein. Site
      A was filled before the other two sites. Calcium competition experiments showed
      that a greater amount of calcium was required to displace terbium from site A
      than from sites B or C. Energy transfer experiments from terbium to holmium
      showed that two of the terbium-binding sites are in close proximity while the
      third site is distant from the other two sites. To determine whether EF-hand 3 or
      4 was responsible for binding of terbium, we examined the terbium binding
      properties of a delta 1,2,5,6 RCaBP construct. The truncated protein RCaBP delta
      1,2,5,6 contained a single terbium-binding site. Analysis of the terbium binding
      to RCaBP delta 1,2,5,6 construct showed that site 4 bound terbium, whereas site 3
      did not. Analysis of the terbium binding characteristics of the proteins suggests
      that EF-hands 1, 4, and 5 of rat brain calbindin D28K are responsible for terbium
      binding.

PMID- 8530461
TI  - The role of tryptophans 371 and 395 in the binding of antibiotics and the
      transport of sugars by the D-galactose-H+ symport protein (GalP) from Escherichia
      coli.
AB  - The interactions between the D-galactose-H+ symporter (GalP) from Escherichia
      coli and the inhibitory antibiotics, cytochalasin B and forskolin, and the
      substrates, D-galactose and H+, have been investigated for the wild-type protein
      and the mutants Trp-371-->Phe and Trp-395-->Phe, so that the roles of these
      residues in the structure-activity relationship could be assessed. Neither
      mutation prevented photolabeling by either [4-3H]cytochalasin B or by 3
      [125I]iodo-4-azidophenethyl-amido-7-O-succinyldesacetylforskolin ([125I]APS
      forskolin). However, measurements of protein fluorescence show that both residues
      are in structural domains, the conformations of which are perturbed by the
      binding of cytochalasin B or forskolin. Moreover, both mutations cause a
      substantial decrease in the affinity of the inward-facing site of the GalP
      protein for cytochalasin B, 10- and 43-fold, respectively, but have little effect
      upon the affinity of this site for forskolin, 0.8- and 2.6-fold reductions,
      respectively. Both these mutations change the equilibrium between the putative
      outward- (T1) and inward-facing (T2) conformations, so that the inward-facing
      form is more favored. They also stabilize a different conformational state, "T3
      antibiotic," in which the initial interactions between the protein and
      antibiotics are tightened. Overall, this has the effect of compensating for the
      reduction in affinity for cytochalasin B, so that the respective overall Kd
      values are 0.74- and 3.5-fold that of the wild type, while causing a slight
      increase, 1.5- and 3.2-fold, respectively, in affinity of the mutants for
      forskolin. The Trp-371-->Phe mutation causes a 15-fold reduction in the affinity
      of the inward-facing site for D-galactose, suggesting that this residue forms
      part of the sugar binding site. In contrast, the Trp-395-->Phe mutation has no
      effect upon the affinity of the inward-facing site for D-galactose. These effects
      may be related to the reduction in galactose-H+ symport activity only in the Trp
      371-->Phe mutant, although it still effects active transport to the same extent
      as the Trp395-->Phe mutant. However, there is a 10-20-fold increase in the Km
      values for energized transport of D-galactose for both mutants.

PMID- 8530462
TI  - Inheritance of unequal numbers of the genes encoding the human neutrophil
      defensins HP-1 and HP-3.
AB  - It is unclear whether the six known human defensin peptides are all encoded by
      separate genes or whether some of them are allelic. Three of the peptides, HP-1,
      HP-2, and HP-3, differ by only one amino acid, and it is thought that HP-2 may
      represent a proteolytic product of HP-1 and/or HP-3. To help determine the
      relationship of these three proteins, we isolated a nearly full-length cDNA
      encoding HP-1 with a sequence very similar to, but different from, the previously
      isolated HP-1 and -3 cDNAs. Gene copy number experiments established that there
      were at least two but fewer than five defensin genes with a high level of
      similarity to the HP-1 cDNA (HP-1/3-like). Three genomic clones were isolated
      that contained two different configurations of the HP-1/3-like sequences.
      Sequencing established that one encoded the HP-1 peptide, whereas the other
      encoded HP-3. Analysis of DNAs obtained from 18 unrelated individuals by Southern
      blot analysis revealed the expected fragments as well as additional fragments
      that were not present in the genomic clones. This suggested the possibility of
      alleles; however, when DNAs from families were examined, these fragments did not
      segregate in an obvious Mendelian fashion. The HP-1/3-like defensin genes are on
      human chromosome 8. Surprisingly, somatic cell hybrid mapping showed that the
      number of HP-1/3-like genes on isolated copies of chromosome 8 was variable. We
      conclude that individuals can inherit versions of chromosome 8 harboring either
      two or three copies of the genes that encode the HP-1, HP-2, and/or HP-3
      peptides.

PMID- 8530463
TI  - Calf 5' to 3' exo/endonuclease must slide from a 5' end of the substrate to
      perform structure-specific cleavage.
AB  - Calf 5' to 3' exo/endonuclease, the counterpart of the human FEN-1 and yeast RTH
      1 nucleases, performs structure-specific cleavage of both RNA and DNA and is
      implicated in Okazaki fragment processing and DNA repair. The substrate for
      endonuclease activity is a primer annealed to a template but with a 5' unannealed
      tail. The results presented here demonstrate that the nuclease must enter the 5'
      end of the unannealed tail and then slide to the region of hybridization where
      the cleavage occurs. The presence of bound protein or a primer at any point on
      the single-stranded tail prevents cleavage. However, biotinylation of a
      nucleotide at the 5' end or internal to the tail does not prevent cleavage. The
      sliding process is bidirectional. If the nuclease slides onto the tail, later
      binding of a primer to the tail traps the nuclease between the primer binding
      site and the cleavage site, preventing the nuclease from departing from the 5'
      end. A model for 5' entry, sliding, and cleavage is presented. The possible role
      of this unusual mechanism in Okazaki fragment processing, DNA repair, and
      protection of the replication fork from inappropriate endonucleolytic cleavage is
      presented.

PMID- 8530464
TI  - The envA permeability/cell division gene of Escherichia coli encodes the second
      enzyme of lipid A biosynthesis. UDP-3-O-(R-3-hydroxymyristoyl)-N
      acetylglucosamine deacetylase.
AB  - The envA gene of Escherichia coli has been shown previously to be essential for
      cell viability (Beall, B. and Lutkenhaus, J. (1987) J. Bacteriol. 169, 5408
      5415), yet it encodes a protein of unknown function. Extracts of strains
      harboring the mutant envA1 allele display 3.5-18-fold reductions in UDP-3-O-acyl
      N-acetylglucosamine deacetylase specific activity. The deacetylase is the second
      enzymatic step of lipid A biosynthesis. The structural gene coding for the
      deacetylase has not been assigned. In order to determine if the envA gene encodes
      the deacetylase, envA was cloned into an isopropyl-1-thio-beta-D
      galactopyranoside-inducible T7-based expression system. Upon induction, a protein
      of the size of envA was highly overproduced, as judged by SDS-PAGE. Direct
      deacetylase assays of cell lysates revealed a concomitant approximately 5,000
      fold overproduction of activity. Assays of the purified, overproduced EnvA
      protein demonstrated a further approximately 5-fold increase in specific
      activity. N-terminal amino acid sequencing of the purified protein showed that
      the first 20 amino acids matched the predicted envA nucleotide sequence.
      Contaminating species were present at less than 1% of the level of the EnvA
      protein. Thus, envA is the structural gene for UDP-3-O-acyl-GlcNAc deacetylase.
      Based on its function in lipid A biosynthesis, we propose the new designation
      lpxC for this gene.

PMID- 8530465
TI  - The mechanism and substrate specificity of the NADPH:flavin oxidoreductase from
      Escherichia coli.
AB  - The NAD(P)H:flavin oxidoreductase from Escherichia coli, Fre, is a monomer of
      26.2 kDa that catalyzes the reduction of free flavins by NADPh or NADH.
      Overexpression in E. coli now allows the preparation of large amounts of pure
      protein. Structural requirements for recognition of flavins as substrates and not
      as cofactors were studied by steady-state kinetics with a variety of flavin
      analogs. The entire isoalloxazine ring was found to be the essential part of the
      flavin molecule for interaction with the polypeptide chain. Methyl groups at C-7
      and C-8 of the isoalloxazine ring and the N-3 of riboflavin also play an
      important role in that interaction, whereas the ribityl chain of the riboflavin
      is not required for binding to the protein. On the other hand, the presence of
      the 2'-OH of the ribityl chain stimulates the NADPH-dependent reaction
      significantly. Moreover, a study of competitive inhibitors for both substrates
      demonstrated that Fre follows a sequential ordered mechanism in which NADPH binds
      first followed by riboflavin. Lumichrome, a very good inhibitor of Fre, may be
      used to inhibit flavin reductase in E. coli growing cells. As a consequence, it
      can enhance the antiproliferative effect of hydroxyurea, a cell-specific
      ribonucleotide reductase inactivator.

PMID- 8530466
TI  - A mutation in the ATP binding domain of rho alters its RNA binding properties and
      uncouples ATP hydrolysis from helicase activity.
AB  - The Escherichia coli mutant rho201 was originally isolated in a genetic screen
      for defects in rho-dependent termination. Cloning and sequencing of this gene
      reveals a single phenylalanine to cysteine mutation at residue 232 in the ATP
      binding domain of the protein. This mutation significantly alters its RNA binding
      properties so that it binds trp t', RNA 100-fold weaker than the wild type
      protein, with a Kd of approximately 1.3 nM. Rho201 binds nonspecific RNA only 3-4
      fold less tightly than it binds trp t', while the wild type differential for
      these same RNAs is 10-20-fold. Curiously, rho201 displays increased secondary
      site RNA activation, with a Km for ribo(C)10 of 0.6 microM, compared to the wild
      type value of 3-4 microM. Although rho201 and the wild type protein hydrolyze ATP
      similarly with poly(C), or trp t' RNA, as cofactors, rho201 has a higher ATPase
      activity when activated by nonspecific RNA. Physically, rho201 displays an
      abnormal conformation detectable by mild trypsin digestion. Despite effective ATP
      hydrolysis, the rho201 mutant is a poor RNA:DNA helicase and terminates
      inefficiently on trp t'. The single F232C mutation thus appears to uncouple the
      protein's ATPase activity from its helicase function, so rho can no longer
      harness available energy for use in subsequent reactions.

PMID- 8530468
TI  - Lec32 is a new mutation in Chinese hamster ovary cells that essentially abrogates
      CMP-N-acetylneuraminic acid synthetase activity.
AB  - LEC29.Lec32 is a glycosylation mutant that was isolated from a selection of
      mutagenized Chinese hamster ovary (CHO) cells for lectin resistance. Compared
      with LEC29 CHO cells, the double mutant exhibited an unusually high sensitivity
      to the toxic lectin, ricin, indicating increased exposure of galactose residues
      on cell surface carbohydrates. Structural analysis of LEC29.Lec32 cellular
      glycoproteins showed a nearly complete lack of sialic acid residues. Genetic
      analysis demonstrated that the lec32 mutation is recessive and novel. Biochemical
      analysis showed that the mutant cells contained less than 5% of the cytidine 5'
      monophosphate N-acetylneuraminic acid (CMP-NeuAc) present in parental CHO cells
      (1.6 nmol/mg of cell protein). A sensitive radiochemical assay used to measure
      CMP-NeuAc synthetase activity showed that the properties of this enzyme in
      parental CHO cells were essentially identical to those of CMP-NeuAc synthetase in
      various mammalian tissues. However, no CMP-NeuAc synthetase activity was detected
      in LEC29.Lec32 extracts. Mixing experiments provided no evidence for an inhibitor
      in the mutant CHO cells, and two revertants, which expressed only the LEC29
      phenotype, had normal CMP-NeuAc synthetase levels. The combined evidence
      indicates that the lec32 mutation resides in either the structural gene encoding
      CMP-NeuAc synthetase or in a gene that regulates the production of active enzyme.

PMID- 8530467
TI  - Identification of a family of closely related human ubiquitin conjugating
      enzymes.
AB  - Two very closely related human E2 ubiquitin conjugating enzymes, UbfH5B and
      UbcH5C, have been identified. These enzymes are products of distinct genes and
      are 88-89% identical in amino acid sequence to the recently described human E2,
      UbcH5 (now designated UbcH5A), UbcH5A-C are homologous to a family of five
      ubiquitin conjugating enzymes from Arabidopsis thaliana, AtUBC8-12. They are also
      closely related to Saccharomyces cerevisiae ScUBC4 and ScUBC5, which are involved
      in the stress response, and play a central role in the targeting of short-lived
      regulatory proteins for degradation. mRNAs encoding UbcH5A-C were co-expressed in
      all cell lines and tissues evaluated, with UbcH5C transcripts generally expressed
      at the highest levels. Analysis of Southern blots suggests that there are likely
      to be other related members of this family. Both UbcH5B and UbcH5C form thiol
      ester adducts with ubiquitin, and have activities similar to UbcH5A and AtUBC8 in
      the conjugation of ubiquitin to target proteins in the presence of the human
      ubiquitin protein ligase E6-AP. These results establish the existence of a highly
      conserved, and widely expressed, family of human ubiquitin conjugating enzymes.

PMID- 8530469
TI  - Topological mimicry of cross-reacting enantiomeric peptide antigens.
AB  - Rabbit polyclonal antibodies against multimeric peptide antigens were found to
      cross-react to a significant extent with topologically related variants of the
      parent antigen, where the chirality of each amino acid residue (inverso
      derivatives), or the peptide sequence orientation (retro derivatives), was
      inverted or where both modifications were simultaneously introduced (retro
      inverso derivatives). All peptide variants displayed similar recognition
      properties for antibodies and similar dose-dependent inhibitory effects on the
      interaction between immobilized parent antigen and corresponding antibodies.
      Importance of peptide side chain topology on antigenicity was evaluated analyzing
      the recognition properties of two sequence-simplified parent peptide variants,
      one lacking of the side chains in the sequence odd position and the other in even
      position. These two variants, prepared introducing glycine residues alternatively
      in the parent peptide sequence, were found to cross-react to a significant extent
      with the original antibody raised against the parent peptide. Analysis of
      molecular models of peptide enantiomeric variants in the elongated all-trans
      configuration suggested that the topological equivalence of alternating side
      chains could lead to the formation of similar recognition surfaces, thus
      mimicking the parent peptide antigenic structure.

PMID- 8530470
TI  - Interference of PR-bound RNA polymerase with open complex formation at PRM is
      relieved by a 10-base pair deletion between the two promoters.
AB  - Bacteriophage lambda promoters PR and PRM direct RNA synthesis in divergent
      orientations from start sites 82 base pairs apart. We had previously determined
      that the presence on the same DNA fragment of a wild type PR promoter interfered
      with the utilization of the PRM promoter. The results reported here concern the
      effects of changing the distance between the start sites by insertion or deletion
      of 5 or 10 base pairs. Three different techniques (run-off transcription, gel
      mobility shift, and permanganate probing) were employed to monitor complex
      formation at PRM. Unexpectedly we find that deletion of 10 base pairs between the
      start sites abolishes the interference, whereas insertion of 10 base pairs does
      not. Deletion of 5 base pairs, however, essentially prevents joint complex
      formation at PR and PRM. These findings suggest several ways in which for the
      wild type separation of the two promoters the utilization of PRM could be
      affected by an RNA polymerase at PR. In addition to direct steric interference,
      these include the obstruction of access to DNA sites necessary for optimal
      contact with the RNA polymerase.

PMID- 8530471
TI  - Kinetics of oxidation of tyrosine and dityrosine by myeloperoxidase compounds I
      and II. Implications for lipoprotein peroxidation studies.
AB  - The oxidation of lipoproteins is considered to play a key role in atherogenesis,
      and tyrosyl radicals have been implicated in the oxidation reaction. Tyrosyl
      radicals are generated in a system containing myeloperoxidase, H2O2, and
      tyrosine, but details of this enzyme-catalyzed reaction have not been explored.
      We have performed transient spectral and kinetic measurements to study the
      oxidation of tyrosine by the myeloperoxidase intermediates, compounds I and II,
      using both sequential mixing and single-mixing stopped-flow techniques. The one
      electron reduction of compound I to compound II by tyrosine has a second order
      rate constant of (7.7 +/- 0.1) x 10(5) M-1 s-1. Compound II is then reduced by
      tyrosine to native enzyme with a second order rate constant of (1.57 +/- 0.06) x
      10(4) M-1 s-1. Our study further revealed that, compared with horseradish
      peroxidase, thyroid peroxidase, and lactoperoxidase, myeloperoxidase is the most
      efficient catalyst of tyrosine oxidation at physiological pH. The second order
      rate constant for the myeloperoxidase compound I reaction with tyrosine is
      comparable with that of its compound I reaction with chloride: (4.7 +/- 0.1) x
      10(6) M-1 s-1. Thus, although chloride is considered the major myeloperoxidase
      substrate, tyrosine is able to compete effectively for compound I. Steady state
      inhibition studies demonstrate that chloride binds very weakly to the tyrosine
      binding site of the enzyme. Coupling of tyrosyl radicals yields dityrosine, a
      highly fluorescent stable compound that had been identified as a possible marker
      for lipoprotein oxidation. We present spectral and kinetic data showing that
      dityrosine is further oxidized by both myeloperoxidase compounds I and II. The
      second order rate constants we determined for dityrosine oxidation are (1.12 +/-
      0.01) x 10(5) M-1 s-1 for compound I and (7.5 +/- 0.3) x 10(2) M-1 s-1 for
      compound II. Therefore, caution must be exercised when using dityrosine as a
      quantitative index of lipoprotein oxidation, particularly in the presence of
      myeloperoxidase and H2O2.

PMID- 8530472
TI  - Variation in the size of nascent RNA cleavage products as a function of
      transcript length and elongation competence.
AB  - RNA polymerase II arrested at specific template locations can be rescued by
      elongation factor SII via RNA cleavage. The size of the products removed from the
      3'-end of the RNA varies. The release of single nucleotides, dinucleotides, and
      larger oligonucleotides has been detected by different workers. Dinucleotides
      tend to originate from SII-independent complexes and 7-14 base products from SII
      dependent complexes (Izban, M. G., and Luse, D. S. (1993) J. Biol. Chem. 268,
      12874-12885). Different modes of cleavage have also been recognized for bacterial
      transcription complexes and are thought to represent important structural
      differences between functionally distinct transcription intermediates. Using an
      elongation complex "walking" technique, we have observed factor-independent
      complexes as they approach and become arrested at an arrest site. Dinucleotides
      or 7-9-base (large) oligonucleotides were released from SII-independent or
      dependent complexes, respectively. The abrupt shift between the release of
      dinucleotide versus larger products accompanied the change from factor-dependent
      to factor-independent elongation, as described by others. However, not all factor
      independent complexes showed cleavage in dinucleotide intervals since
      oligonucleotides 2-6 bases long were also liberated from elongation-competent
      complexes. These were all 5'-coterminal oligonucleotides indicating that a
      preferred phosphodiester bond is targeted for cleavage in a series of related
      complexes. This is consistent with recent models postulating a large product
      binding site that can hold RNA chains whose size increases as a function of chain
      polymerization. A specific transitional complex was identified that acquired the
      ability to cleave in a large increment one base insertion event prior to
      attaining the arrested configuration.

PMID- 8530473
TI  - RNA-binding proteins that specifically recognize the selenocysteine insertion
      sequence of human cellular glutathione peroxidase mRNA.
AB  - Translational incorporation of the unusual amino acid selenocysteine in
      eukaryotes requires a coding region UGA codon (which otherwise serves as a
      termination signal), a selenocysteine insertion sequence (SECIS) in the 3'
      untranslated region of the mRNA, and selenocysteyl-tRNA. The mechanisms involved
      in SECIS recognition by the eukaryotic translational machinery remain unknown. We
      report the detection of RNA-binding proteins that specifically recognize the
      SECIS from human cellular glutathione peroxidase (GPX1) transcripts. RNA gel
      shift assays showed three retarded bands after incubation with COS-1 whole cell
      lysate or S-100 cytosol fraction or with extracts from hepatoma cell lines HepG2
      and Hep3B. The specificity of the binding was demonstrated by competition by cold
      unlabeled SECIS RNA and by lack of competition by other RNA species with similar
      stem-loop secondary structures, such as the human immunodeficiency virus (HIV)
      transactivation-response region of HIV mRNA element, and mutated SECIS
      constructs. UV cross-linking and SDS-polyacrylamide gel electrophoresis revealed
      at least two proteins, with estimated molecular masses of 55,000 and 65,000 Da,
      that bind to the SECIS. Examination of a series of insertion and deletion SECIS
      mutants indicated recognition of the SECIS primarily through the basal stem
      region, although the upper stem, loop, and two of three short conserved sequences
      also appear to contribute to the affinity of the binding.

PMID- 8530474
TI  - Purification and characterization of a novel ADP-dependent glucokinase from the
      hyperthermophilic archaeon Pyrococcus furiosus.
AB  - Pyrococcus furiosus uses a modified Embden-Meyerhof pathway during growth on poly
      or disaccharides. Instead of the usual ATP-dependent glucokinase, this pathway
      involves a novel ADP-dependent (AMP-forming) glucokinase. The level of this
      enzyme and some other glycolytic enzymes appeared to be closely regulated by the
      substrate. Growth on cellobiose resulted in a high specific activity of 0.96
      units mg-1, whereas on pyruvate a 10-fold lower activity was found. The ADP
      dependent glucokinase was purified 1350-fold to homogeneity. The oxygen-stable
      enzyme had a molecular mass of 93 kDa and was composed of two identical subunits
      (47 kDa). The glucokinase was highly specific for ADP, which could not be
      replaced by ATP, phosphoenolpyruvate, GDP, PPi, or polyphosphate. D-Glucose could
      be replaced only by 2-deoxy-D-glucose, albeit with a low efficiency. The Km
      values for D-glucose and ADP were 0.73 and 0.033 mM, respectively. An optimum
      temperature of 105 degrees C and a half-life of 220 min at 100 degrees C are in
      agreement with the requirements of this hyperthermophilic organism. The
      properties of the glucokinase are compared to those of less thermoactive
      gluco/hexokinases.

PMID- 8530475
TI  - Identification of amino acid residues critical for catalysis and cosubstrate
      binding in the flavonol 3-sulfotransferase.
AB  - The comparison of the deduced amino acid sequences of plant and animal
      sulfotransferases (ST) has allowed the identification of four well conserved
      regions, and previous experimental evidence suggested that regions I and IV might
      be involved in the binding of the cosubstrate, 3'-phosphoadenosine 5'
      phosphosulfate (PAPS). Moreover, region IV is homologous to the glycine-rich
      phosphate binding loop (P-loop) motif known to be involved in nucleotide
      phosphate binding in several protein families. In this study, the function of
      amino acid residues within these two regions was investigated by site-directed
      mutagenesis of the plant flavonol 3-ST. In region I, our results identify Lys59
      as critical for catalysis, since replacement of this residue with alanine
      resulted in a 300-fold decrease in specific activity, while a 15-fold reduction
      was observed after the conservative replacement with arginine. Photoaffinity
      labeling of K59R and K59A with [35S]PAPS revealed that Lys59 is not required for
      cosubstrate binding. However, the K59A mutant had a reduced affinity for 3'
      phosphoadenosine 5'-phosphate (PAP)-agarose, suggesting that Lys59 may
      participate in the stabilization of an intermediate during the reaction. In
      region IV, all substitutions of Arg276 resulted in a marked decrease in specific
      activity. Conservative and unconservative replacements of Arg276 resulted in weak
      photoaffinity labeling with [35S]PAPS and the R276A/T73A and R276E enzymes
      displayed reduced affinities for PAP-agarose, suggesting that the Arg276 side
      chain is required to bind the cosubstrate. The analysis of the kinetic constants
      of mutant enzymes at residues Lys277, Gly281, and Lys284 allowed to confirm that
      region IV is involved in cosubstrate binding.

PMID- 8530476
TI  - Activation of Ca2+/calmodulin-dependent protein kinase (CaM-kinase) IV by CaM
      kinase kinase in Jurkat T lymphocytes.
AB  - Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV), a member of the CaM
      kinase family involved in transcriptional regulation, is stimulated by Ca2+/CaM
      but also requires phosphorylation by a CaM-kinase kinase for full activation. In
      this study we investigated the physiological role of a CaM-kinase cascade in
      Jurkat T human lymphocytes through antigen receptor (CD3) signaling. Total and
      Ca(2+)-independent CaM-kinase IV activities were increased 8-14-fold by anti-CD3
      antibody. This CD3-mediated activation involved phosphorylation since the
      immunoprecipitated CaM-kinase IV from stimulated Jurkat cells could be
      subsequently inactivated in vitro by protein phosphatase 2A. CaM-kinase IV
      immunoprecipitated from unstimulated Jurkat cells or CD3-negative mutant Jurkat
      cells could be activated in vitro 10-40-fold by CaM-kinase kinase purified from
      rat brain or thymus, whereas CaM-kinase IV from CD3-stimulated wild-type Jurkat
      cells was only activated to 2-3-fold by exogenous CaM-kinase kinase. CaM-kinase
      IV activation was triggered by Ca2+ acting through calmodulin since activation
      could also be elicited by ionomycin treatment, and CD3-mediated activation was
      blocked by the calmodulin antagonist calmidazolium. These data are consistent
      with a CaM-kinase cascade in which CaM-kinase IV is activated by a CaM-kinase
      kinase cascade triggered by elevated intracellular calcium in Jurkat cells.

PMID- 8530477
TI  - Purification, characterization, and molecular cloning of a novel rat liver
      Dopa/tyrosine sulfotransferase.
AB  - A novel sulfotransferase was purified from the rat liver cytosol to
      electrophoretic homogeneity via five column chromatography steps (hydroxylapatite
      I, DEAE Bio-Gel, ATP-agarose I, hydroxylapatite II, and ATP-agarose II). The
      minimum molecular weight of the purified enzyme was determined by sodium dodecyl
      sulfatepolyacrylamide gel electrophoresis to be approximately 33,000. Gel
      filtration chromatography revealed a native molecular weight of approximately
      34,000, indicating the enzyme being present in the monomeric form. The purified
      sulfotransferase displayed enzymatic activities, with a pH optimum of 9.25,
      toward various tyrosine and 3,4-dihydroxyphenylalanine (Dopa) isomers, except DL
      ortho-tyrosine. Thyroid hormones, as well as dopamine and p-nitrophenol, could
      also be used as substrates. The apparent Km value of the enzyme (designated the
      Dopa/tyrosine sulfotransferase) for L-Dopa, determined at a constant 14 microM of
      3'-phosphoadenosine 5'-phosphosulfate, was 0.76 mM. The intact enzyme was found
      to be N-blocked when subjected to N-terminal sequencing. Three internal partial
      amino acid sequences, obtained by analyzing its proteolytic fragments, were found
      to be distinct from the homologous sequences of other known rat liver
      sulfotransferases. The deduced amino acid sequence of a full-length cDNA isolated
      from a rat liver cDNA library confirmed the identity of the Dopa/tyrosine
      sulfotransferase as a new type of aryl sulfotransferase. Upon transfection of COS
      7 cells with an expression vector (pMSG-CMV) harboring the full-length cDNA, a 33
      kDa protein displaying enzymatic and immunological properties similar to those of
      the purified Dopa/tyrosine sulfotransferase was expressed.

PMID- 8530478
TI  - Intermolecular autolytic cleavage can contribute to the activation of
      progelatinase A by cell membranes.
AB  - Membrane-type matrix metalloproteinase (MT-MMP) messenger RNA and protein
      expression were shown to be elevated in human fibroblasts following treatment
      with concanavalin A, coincident with the induction of the ability to process
      progelatinase A. CHO cells transfected with the cDNA for MT-MMP were able to
      process both wild type progelatinase A and a catalytically inactive mutant, E375A
      progelatinase A. Both proenzymes were converted to a 68-kDa intermediate
      (reducing gels) form, but only the wild type enzyme was processed further to a 66
      kDa end product. In contrast, both forms of progelatinase were processed via the
      68-kDa intermediate to 66 kDa by concanavalin A-stimulated fibroblasts. Further
      study of the processing of E375A progelatinase A by plasma membrane preparations
      from concanavalin A-stimulated fibroblasts showed that addition of active
      gelatinase A enhanced processing to the mature form. It was concluded that cell
      membrane-mediated activation of progelatinase A could be via a cascade involving
      both MT-MMP and intermolecular autolytic cleavage.

PMID- 8530479
TI  - Protein loop grafting to construct a variant of tissue-type plasminogen activator
      that binds platelet integrin alpha IIb beta 3.
AB  - Protein-protein interactions can be guided by contacts between surface loops
      within proteins. We therefore investigated the hypothesis that novel protein
      protein interactions could be created using a strategy of "loop grafting" in
      which the amino acid sequence of a biologically active, flexible loop on one
      protein is used to replace a surface loop present on an unrelated protein. To
      test this hypothesis we replaced a surface loop within an epidermal growth factor
      module with the complementarity-determining region of a monoclonal antibody.
      Specifically, the HCDR3 from Fab-9, an antibody selected to bind the beta 3
      integrins with nanomolar affinity (Smith, J. W., Hu, D., Satterthwait, A., Pinz
      Sweeney, S., and Barbas, C. F., III (1994) J. Biol. Chem. 269, 32788-32795), was
      grafted into the epidermal growth factor-like module of human tissue-type
      plasminogen activator (t-PA). The resulting variant of t-PA bound to the platelet
      integrin alpha IIb beta 3 with nanomolar affinity, retained full enzymatic
      activity, and was stimulated normally by the physiological co-factor fibrin.
      Binding of the novel variant of t-PA to integrin alpha IIb beta 3 was dependent
      on the presence of divalent cations and was inhibited by an RGD-containing
      peptide, demonstrating that, like the donor antibody, the novel t-PA binds
      specifically to the ligand-binding site of the integrin. These findings suggest
      that surface loops within protein modules can, at least in some cases, be
      interchangeable and that phage display can be combined with loop grafting to
      direct proteins, at high affinity, to selected targets. In principle, these
      targets could include not only other proteins but also peptides, nucleic acids,
      carbohydrates, lipids, or even uncharacterized markers of specific cell types,
      tissues, or viruses.

PMID- 8530480
TI  - Processive post-translational modification. Vitamin K-dependent carboxylation of
      a peptide substrate.
AB  - Mass spectrometry has been used to demonstrate that vitamin K-dependent
      carboxylation is a processive post-translational modification (i.e. multiple
      carboxylations occur during a single association between enzyme and substrate).
      Purified vitamin K-dependent carboxylase can carboxylate as many as 12 glutamate
      residues in FIXQ/S, a peptide substrate based on amino acids -18 to 41 of the
      human blood clotting enzyme factor IX. Mass spectrometry was used to determine
      the number of gamma-carboxyl groups added to FIXQ/S by the carboxylase during an
      in vitro reaction. Despite the fact that most substrate molecules in a reaction
      were uncarboxylated, almost all carboxylated FIXQ/S molecules were carboxylated
      many times. This observation can only be explained by two types of mechanisms. In
      a processive mechanism, multiple carboxylations could occur during a single
      substrate binding event. Alternatively, a distributive mechanism could result in
      the observed behavior if the initial carboxylation event results in a substrate
      that is additionally carboxylated far more efficiently than the uncarboxylated
      FIXQ/S. Kinetic experiments and arguments were used to show that the vitamin K
      dependent carboxylase is not distributive but rather is one of the first well
      documented examples of an enzyme that catalyzes a processive post-translation
      modification.

PMID- 8530482
TI  - The C-terminal region of the UvrB protein of Escherichia coli contains an
      important determinant for UvrC binding to the preincision complex but not the
      catalytic site for 3'-incision.
AB  - The UvrABC endonuclease from Escherichia coli repairs damage in the DNA by dual
      incision of the damaged strand on both sides of the lesion. The incisions are in
      an ordered fashion, first on the 3'-side and next on the 5'-side of the damage,
      and they are the result of binding of UvrC to the UvrB-DNA preincision complex.
      In this paper, we show that at least the C-terminal 24 amino acids of UvrB are
      involved in interaction with UvrC and that this binding is important for the 3'
      incision. The C-terminal region of UvrB, which shows homology with a domain of
      the UvrC protein, is part of a region that is predicted to be able to form a
      coiled-coil. We therefore propose that UvrB and UvrC interact through the
      formation of such a structure. The C-terminal region of UvrB only interacts with
      UvrC when present in the preincision complex, indicating that the conformational
      change in UvrB accompanying the formation of this complex exposes the UvrC
      binding domain. Binding of UvrC to the C-terminal region of UvrB is not important
      for the 5'-incision, suggesting that for this incision a different interaction of
      UvrC with the UvrB-DNA complex is required. Truncated UvrB mutants that lack up
      to 99 amino acids from the C terminus still give rise to significant incision (1
      2%), indicating that this C-terminal region of UvrB does not participate in the
      formation of the active site for 3'-incision. This region, however, contains the
      residue (Glu-640) that was proposed to be involved in 3'-catalysis, since a
      mutation of the residue (E640A) fails to promote 3'-incision (Lin, J.J.,
      Phillips, A.M., Hearst, J.E., and Sancar, A. (1992) J. Biol. Chem. 267, 17693
      17700). We have isolated a mutant UvrB with the same E640A substitution, but this
      protein shows normal UvrC binding and incision in vitro and also results in
      normal survival after UV irradiation in vivo. As a consequence of these results,
      it is still an open question as to whether the catalytic site for 3'-incision is
      located in UvrB, in UvrC, or is formed by both proteins.

PMID- 8530481
TI  - The Y-box motif mediates redox-dependent transcriptional activation in mouse
      cells.
AB  - We show here that the OxyR response element (ORE) in the bacterial oxyR promoter
      can also function as a redox-dependent enhancer in mammalian cells. Fusion of ORE
      to an SV40 basal promoter driving chloramphenicol acetyltransferase (CAT)
      expression confers H2O2 inducibility to expression of the cat gene in mouse Hepa
      1 hepatoma cells. Nuclear extracts from these cells contain DNA-binding proteins
      that specifically interact with ORE DNA, cannot be completed by cognate
      oligonucleotides to AP-1 or NF kappa B, and are constitutively expressed, since
      treatment with H2O2 causes no detectable changes in binding activity or DNA
      protein interaction. Recombinant cDNA clones that express ORE-binding proteins
      were isolated from a mouse hepatoma expression library and found to be
      representatives of two different members of the murine Y-box family of
      transcription factors. Canonical Y-box and ORE oligonucleotides compete with each
      other for binding to Y-box proteins in gel shift assays and antibodies to FRGY2,
      a Xenopus Y-box protein, supershift both Y-box and ORE DNA-protein complexes. In
      addition, antisense oligonucleotides to mouse YB-1 mRNA abolish induction of ORE
      mediated cat expression by H2O2, and luciferase reporter constructs containing
      ORE, or the Y-box from the human MHC class II HLA-DQ gene, exhibit identical dose
      dependent H2O2 inducibilities, which can be abolished by addition of 2
      mercaptoethanol to the culture medium. These results suggest that the Y-box
      proteins may be an integral component of a eukaryotic redox signaling pathway.

PMID- 8530483
TI  - Solution structure of the sequence-specific HMG box of the lymphocyte
      transcriptional activator Sox-4.
AB  - Two groups of HMG box proteins are distinguished. Proteins in the first group
      contain multiple HMG boxes, are non-sequence-specific, and recognize structural
      features as found in cruciform DNA and cross-over DNA. The abundant chromosomal
      protein HMG-1 belongs to this subgroup. Proteins in the second group carry a
      single HMG box with affinity for the minor groove of the heptamer motif AACAAAG
      or variations thereof. A solution structure for the non-sequence-specific C
      terminal HMG box of HMG-1 has recently been proposed. Now, we report the solution
      structure of the sequence-specific HMG-box of the SRY-related protein Sox-4. NMR
      analysis demonstrated the presence of three alpha-helices (Val10-Gln22, Glu30
      Leu41 and Phe50-Tyr65) connected by loop regions (Ser23-Ala49 and Leu42-Pro49).
      Helices I and II are positioned in an antiparallel mode and form one arm of the
      HMG box. Helix III is less rigid, makes an average angle of about 90 degrees with
      helices I and II, and constitutes the other arm of the molecule. As in HMG1B, the
      overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster
      of conserved, mainly aromatic residues.

PMID- 8530485
TI  - Spectroscopic and kinetic properties of unphosphorylated rat hepatic
      phenylalanine hydroxylase expressed in Escherichia coli. Comparison of resting
      and activated states.
AB  - The non-heme iron-dependent metalloenzyme, rat hepatic phenylalanine hydroxylase
      (EC 1.14.16.1; phenylalanine 4-monooxygenase (PAH) was overexpressed in
      Escherichia coli and purified to homogeneity, allowing a detailed comparison of
      the kinetic, hydrodynamic, and spectroscopic properties of its allosteric states.
      The homotetrameric recombinant enzyme, which is highly active and contains 0.7
      0.8 iron atoms per subunit, is identical to the native enzyme in several
      properties: Km, 6-methyltetrahydropterin = 61 microM and L-Phe = 170 microM; Vmax
      = 9 s-1 (compared to 45 microM, 180 microM, and 13 s-1 for the rat hepatic
      enzyme). L-Phe and lysolecithin treatment induce the rPAHT-->rPAHR (where r is
      recombinant) allosteric transformation necessary for rPAH activity.
      Characteristic changes in the fluorescence spectra, increased hydrophobicity, a
      large activation energy barrier, and a 10% volume increase of the tetrameric
      structure are consistent with a significant reorganization of the protein
      following allosteric activation. However, optical and EPR spectroscopic data
      suggest that only minor changes occur in the primary coordination sphere
      (carboxylate/histidine/water) of the catalytic iron center. Detailed steady state
      kinetic investigations, using 6-methyltetrahydropterin as cofactor and
      lysolecithin as activator, indicate rPAH follows a sequential mechanism. A
      catalytic Arrhenius Eact of 14.6 +/- 0.3 kcal/mol subunit was determined from
      temperature-dependent stopped-flow kinetics data. rPAH inactivates during L-Phe
      hydroxylation with a half-life of 4.3 min at 25 degrees C, corresponding to an
      Arrhenius Eact of 10 +/- 1 kcal/mol subunit for the inactivation process.
      Catechol binding (2.4 x 10(6) M-1) is shown to occur only at catalytically
      competent iron sites. Ferrous rPAH binds NO, giving rise to an ST = 3/2 spin
      system.

PMID- 8530486
TI  - Site-directed mutagenic alteration of potential active-site residues of the A
      subunit of Escherichia coli heat-labile enterotoxin. Evidence for a catalytic
      role for glutamic acid 112.
AB  - Escherichia coli heat-labile enterotoxin (LT) and the related cholera toxin exert
      their effects on eukaryotic cells through the ADP-ribosylation of guanine
      nucleotide-binding proteins of the adenylate cyclase complex. The availability of
      the crystal structure for LT has permitted the tentative identification of
      residues that lie within or are vicinal to a presumptive NAD(+)-binding site and
      thus may play a role in substrate binding or catalysis. Using a plasmid clone
      encoding the A subunit of LT, we have introduced substitutions at such potential
      active-site residues and analyzed the enzymatic properties of the resultant
      mutant analogs. Enzymatic analyses, employing both transducin and agmatine as
      acceptor substrates, revealed that substitutions at serine 61, glutamic acid 110,
      and glutamic acid 112 resulted in reduction of enzyme activity to < 10% of wild
      type levels. Kinetic analyses indicated that alteration of these sites affected
      the catalytic rate of the enzyme and had little or no effect on the binding of
      either NAD+ or agmatine. Of the mutant analogs analyzed, only glutamic acid 112
      appeared to represent an essential catalytic residue as judged by the relative
      effects on kcat and kcat/Km. The results provide formal evidence that glutamic
      acid 112 of the A subunit of LT represents a functional homolog or analog of
      catalytic glutamic acid residues that have been identified in several other
      bacterial ADP-ribosylating toxins and that it may play an essential role in
      rendering NAD+ susceptible to nucleophilic attack by an incoming acceptor
      substrate.

PMID- 8530484
TI  - The tonoplast-associated citrate binding protein (CBP) of Hevea brasiliensis.
      Photoaffinity labeling, purification, and cloning of the corresponding gene.
AB  - A detailed comparison of citrate uptake into the vacuole-like lutoids of rubber
      tree (Hevea brasiliensis Muell. Arg.) and of malate and citrate transport into
      barley (Hordeum vulgare L.) vacuoles revealed very similar transport
      specificities. In order to identify proteins mediating the transport, two
      photoreactive analogues (N'-(2-hydroxy-5-azido)-diazo-N-3,5-benzenedicarboxylic
      acid and 5-azidoisophthalic acid) of malate/citrate were synthesized and found to
      efficiently inhibit citrate uptake into barley vacuoles (Ki = 18 microM) and
      Hevea lutoid vesicles (Ki = 27 microM). In vacuoles from both plant species,
      these photoaffinity probes specifically labeled a single protein with a molecular
      mass of 23.6 kDa. This citrate binding protein (CBP) was purified to homogeneity
      from Hevea lutoids, and amino acid sequences were determined for NH2-terminal and
      tryptic peptides. Using degenerate oligonucleotides of the NH2-terminal sequence,
      a cDNA coding for the CBP protein of Hevea was isolated. The cDNA codes for a
      precursor protein of 238 amino acids, containing an NH2-terminal 31-amino acid
      signal sequence for endoplasmic reticulum targeting, a prerequisite for vacuolar
      localization. The mature CBP does not show significant sequence similarities to
      any known primary protein structure and thus represents a member of a novel class
      of proteins.

PMID- 8530488
TI  - A novel GTPase-activating protein for R-Ras.
AB  - R-Ras, belonging to the Ras small GTP-binding protein superfamily, has been
      implicated in regulation of various cell functions such as gene expression, cell
      proliferation, and apoptotic cell death. In the present study, we purified an R
      Ras-interacting protein with molecular mass of about 98 kDa (p98) from bovine
      brain cytosol by glutathione S-transferase (GST)-R-Ras affinity column
      chromatography. This protein bound to GTP gamma S (guanosine 5'-(3-O
      thio)triphosphate, a nonhydrolyzable GTP analog).R-Ras but not to GDP.R-Ras, GTP
      gamma S.R-Ras with a mutation in the effector domain (R-RasA64), GTP gamma S.Ha
      Ras, or GTP gamma S.RalA. We obtained a cDNA encoding p98 on the basis of its
      partial amino acid sequences. The predicted protein consists of 834 amino acids
      whose calculated mass, 95,384 Da, is close to the apparent molecular mass of p98.
      The amino acid sequence shows a high degree of sequence similarity to the entire
      sequence of Gap1m, one of the GTPase-activating proteins (GAP) for Ha-Ras. A
      recombinant protein consisting of the GAP-related domain of p98 fused to maltose
      binding protein stimulated GTPase activity of R-Ras, and showed a weak effect on
      that of Ha-Ras but not that of Rap1 or Rho. These results clearly indicate that
      p98 is a novel GAP for R-Ras. Thus, we designated this protein as R-Ras GAP.

PMID- 8530487
TI  - Purification of a new clathrin assembly protein from bovine brain coated vesicles
      and its identification as myelin basic protein.
AB  - The multimeric clathrin assembly proteins AP-1 and AP-2 with molecular masses of
      approximately 270 kDa and the monomeric clathrin assembly proteins AP180 and
      auxilin with molecular masses of approximately 90 kDa catalyze the assembly of
      clathrin into artificial clathrin baskets under physiological conditions. We have
      now identified a much smaller approximately 20-kDa clathrin assembly protein in
      0.5 M Tris, pH 7.0, extracts of bovine-brain coated vesicles and purified it to
      near homogeneity. A polyclonal antibody against this protein did not cross-react
      with any of the other assembly proteins, and sequencing data suggest that this
      new protein is similar or identical to myelin basic protein (MBP). At a molar
      ratio of 3 molecules per clathrin triskelion, MBP catalyzes polymerization of
      clathrin into artificial baskets that appear structurally similar to the baskets
      assembled by the other assembly proteins. In addition, like the other baskets,
      the clathrin-MBP baskets are uncoated by hsp70. MBP represents a significant
      fraction of the total assembly protein activity present in 0.5 M Tris, pH 7.0,
      extracts of coated vesicles. It is not clear if it acts as an assembly protein in
      vivo, but because it is well characterized and easily available, MBP will be a
      useful protein to investigate the mechanism of clathrin assembly and disassembly
      in vitro.

PMID- 8530489
TI  - Differential modulation of mitogen-activated protein (MAP) kinase/extracellular
      signal-related kinase kinase and MAP kinase activities by a mutant epidermal
      growth factor receptor.
AB  - A paradigm has been established whereby mutant tyrosine kinase receptors such as
      the v-erbB and v-fms gene products function as oncoproteins in the absence of
      ligand. A spontaneously occurring deletional mutant of the human epidermal growth
      factor receptor (EGFR-vIII) has been isolated from astrocytic neoplasms and
      transforms NIH3T3 cells in the absence of ligand. The EGFRvIII is constitutively
      complexed with the majority of cellular GRB2, suggesting a link to the Ras
      Mitogen-activated protein (MAP) kinase pathway (D. Moscatello, R. B. Montgomery,
      P. Sundareshan, H. McDanel, M. Y. Wong, and A. J. Wong, submitted for
      publication). In this report, we document that expression of EGFRvIII in
      fibroblasts is associated with downstream activation of mitogen-activated protein
      (MAP) kinase/extracellular signal-regulated kinase (MEK) and modest activation of
      p42 and p44 MAP kinases. The presence of EGFRvIII suppresses activation of p42
      and p44 MAP kinases by phorbol 12-myristate 13-acetate (PMA) and serum; however,
      MEK activation by PMA is not suppressed by EGFRvIII. Basal and PMA-stimulated MAP
      kinase activity in EGFRvIII-transfected cells is augmented by the tyrosine
      phosphatase inhibitor sodium vanadate. EGFR-vIII is capable of transducing
      downstream signals through MAP kinase as evidenced by activation of cytoplasmic
      phospholipase A2 at levels similar to that induced by intact EGFR. Our results
      suggest that EGFR-vIII constitutively activates downstream signal transduction
      through MAP kinase, and this chronic stimulation of the MAP kinase pathway may
      represent one means by which mutant EGFR transduces an oncogenic signal.

PMID- 8530490
TI  - Uncoupled packaging of targeting and cargo molecules during transport vesicle
      budding from the endoplasmic reticulum.
AB  - Formation of vesicular intermediates in protein transport between the endoplasmic
      reticulum and the Golgi apparatus involves a mechanism that sorts and packages
      two classes of molecules into transport vesicles: targeting molecules, which are
      required for targeting and consumption of vesicular intermediates, and cargo
      proteins. In order to examine the importance of cargo in this packaging reaction,
      we developed an in vitro assay that quantifies vesicle formation based on
      segregation of targeting molecules. Here we document that endoplasmic reticulum
      devoid of cargo proteins is competent in the formation and release of targeting
      molecule-containing vesicles in a fashion indistinguishable from its normal
      counterpart. This observation implies that packaging of cargo proteins may be
      uncoupled from the recruitment of targeting molecules during vesicle budding from
      the endoplasmic reticulum. Using the same assay, we demonstrate that the
      packaging of targeting molecules into vesicles is not dependent on the lumenal
      chaperone, BiP (Kar2p).

PMID- 8530491
TI  - Mitochondrial receptor complex protein. The intermembrane space domain of yeast
      MAS17 is not essential for its targeting or function.
AB  - MAS17 (MAS22) is an essential component of the import receptor complex in the
      yeast mitochondrial outer membrane. MAS17 consists of three distinct domains: the
      N-terminal cytosolic domain, the internal membrane-spanning domain, and the C
      terminal intermembrane space domain. In the present study, we examined the roles
      of the C-terminal domain of MAS17, which is rich in acidic amino acids, in
      protein import into mitochondria both in vivo and in vitro. Cells expressing
      MAS17 delta 120-152, a mutant MAS17 lacking the C-terminal acidic domain, could
      grow as fast as those expressing wild-type MAS17, while cells expressing MAS17
      delta 97-152, a mutant MAS17 lacking both the intermembrane space and the
      membrane-spanning domains, stopped growing as soon as wild-type MAS17 was
      depleted. MAS17 delta 120-152 was correctly integrated into the mitochondrial
      outer membrane like wild-type MAS17. Mitochondria containing MAS17 delta 120-152
      instead of wild-type MAS17 could import both authentic and artificial
      mitochondrial precursor proteins nearly as efficiently as wild-type mitochondria
      in vitro. These results suggest that the C-terminal intermembrane space domain of
      MAS17 is not essential for targeting or functions of MAS17.

PMID- 8530492
TI  - pH-dependent conformational properties of saposins and their interactions with
      phospholipid membranes.
AB  - Saposins A, B, C, and D are small lysosomal glycoproteins released by proteolysis
      from a single precursor polypeptide, prosaposin. We have presently investigated
      the conformational states of saposins and their interaction with membranes at
      acidic pH values similar to those present in lysosomes. With the use of phase
      partitioning in Triton X-114, experimental evidence was provided that, upon
      acidification, saposins (Sap) A, C, and D acquire hydrophobic properties, while
      the hydrophilicity of Sap B is apparently unchanged. The pH-dependent exposure of
      hydrophobic domains of Sap C and D paralleled their pH-dependent binding to large
      unilamellar vesicles composed of phosphatidylcholine, phosphatidylserine, and
      cholesterol. In contrast, the binding of Sap A to the vesicles was very
      restricted, in spite of its increased hydrophobicity at low pH. A low affinity
      for the vesicles was also shown by Sap B, a finding consistent with its apparent
      hydrophilicity both at neutral and acidic pH. At the acidic pH values needed for
      binding, Sap C and D powerfully destabilized the phospholipid membranes, while
      Sap A and B minimally affected the bilayer integrity. In the absence of the
      acidic phospholipid phosphatidylserine, the induced destabilization markedly
      decreased. Of the four saposins, only Sap C was able to promote the binding of
      glucosylceramidase to phosphatidylserine-containing membranes. This result is
      consistent with the notion that Sap C is specifically required by
      glucosylceramidase to exert its activity. Our finding that an acidic environment
      induces an increased hydrophobicity in Sap A, C, and D, making the last two
      saposins able to interact and perturb phospholipid membranes, suggests that this
      mechanism might be relevant to the mode of action of saposins in lysosomes.

PMID- 8530493
TI  - Systematic deletion analysis of ricin A-chain function. Single amino acid
      deletions.
AB  - The A-chain of ricin is a cytotoxic RNA N-glycosidase that inactivates ribosomes
      by depurination of the adenosine at position 4324 in 28 S rRNA. Of the 267 amino
      acids in the protein, 222 could be deleted, in one or another of 74 mutants,
      without the loss of the capacity to catalyze hydrolysis of a single specific
      nucleotide in rRNA (Morris, K. N., and Wool, I. G. (1992) Proc. Natl. Acad. Sci.
      U.S.A. 89, 4869-4873). The 45 amino acids that could not be omitted when the
      deletions were in sets of 20, 5, or 2 residues have now been deleted one at a
      time; 9 of these deletion mutants retained activity. A RNP-like structural motif
      in ricin A-chain that may mediate binding to ribosomal RNA has been identified.

PMID- 8530494
TI  - Allosteric modulation by tertiary structure in mammalian hemoglobins.
      Introduction of the functional characteristics of bovine hemoglobin into human
      hemoglobin by five amino acid substitutions.
AB  - Bovine erythrocytes do not contain 2,3-diphosphoglycerate, the principal
      allosteric effector of human hemoglobin. Bovine hemoglobin has a lower oxygen
      affinity than human hemoglobin and is regulated by physiological concentrations
      of chloride (Fronticelli, C., Bucci, E., and Razynska, A. (1988) J. Mol. Biol.
      202, 343-348). It has been proposed that the chloride regulation in bovine
      hemoglobin is introduced by particular amino acid residues located in the amino
      terminal region of the A helix and in the E helix of the beta subunits
      (Fronticelli, C. (1990) Biophys. Chem. 37, 141-146). In accordance with this
      proposal we have constructed two mutant human hemoglobins,
      beta(V1M+H2deleted+T4I+P5A) and beta(V1M+H2deleted+T4I+P5A+A76K). These are the
      residues present at the proposed locations in bovine hemoglobin except for
      isoleucine at position 4. Oxygen binding studies demonstrate that these mutations
      have introduced into human hemoglobin the low oxygen affinity and chloride
      sensitivity of bovine hemoglobin and reveal the presence of a previously
      unrecognized allosteric mechanism of oxygen affinity regulation where all the
      interactions responsible for the lowered affinity and chloride binding appear to
      be confined to individual beta subunits.

PMID- 8530495
TI  - Molecular and physiological effects of overexpressing striated muscle beta
      tropomyosin in the adult murine heart.
AB  - Tropomyosins comprise a family of actin-binding proteins that are central to the
      control of calcium-regulated striated muscle contraction. To understand the
      functional role of tropomyosin isoform differences in cardiac muscle, we
      generated transgenic mice that overexpress striated muscle-specific beta
      tropomyosin in the adult heart. Nine transgenic lines show a 150-fold increase in
      beta-tropomyosin mRNA expression in the heart, along with a 34-fold increase in
      the associated protein. This increase in beta-tropomyosin message and protein
      causes a concomitant decrease in the level of alpha-tropomyosin transcripts and
      their associated protein. There is a preferential formation of the alpha beta
      heterodimer in the transgenic mouse myofibrils, and there are no detectable
      alterations in the expression of other contractile protein genes, including the
      endogenous beta-tropomyosin isoform. When expression from the beta-tropomyosin
      transgene is terminated, alpha-tropomyosin expression returns to normal levels.
      No structural changes were observed in these transgenic hearts nor in the
      associated sarcomeres. Interestingly, physiological analyses of these hearts
      using a work-performing model reveal a significant effect on diastolic function.
      As such, this study demonstrates that a coordinate regulatory mechanism exists
      between alpha- and beta-tropomyosin gene expression in the murine heart, which
      results in a functional correlation between alpha- and beta-tropomyosin isoform
      content and cardiac performance.

PMID- 8530496
TI  - Multiple neuron-specific enhancers in the gene coding for the human neurofilament
      light chain.
AB  - To define DNA regions involved in the neuron-specific expression of the
      neurofilament light (NF-L) gene, we generated transgenic mice bearing different
      NF-L constructs. A 4.9-kilobase human NF-L fragment including -292 base pairs of
      5'-flanking sequences contained sufficient elements for nervous system expression
      in transgenic mice. Deletion of introns 1 and 2 from this 4.9-kilobase DNA
      fragment resulted in reduced levels of transgene expression in the cortex, while
      deletion of intron 3 had little effect. Both introns 1 and 2 could act
      independently as enhancers to confer neuronal expression of the basal heat shock
      promoter (hsp68) fused to lacZ in transgenic mice. The hNF-L basal promoter (-292
      base pairs) was found to contain elements for directing neuronal expression of
      either the lacZ reporter gene or an intronless hNF-L construct. Sequence
      comparison revealed that intron 1, intron 2, and the basal human NF-L promoter
      all contain an ETS-like motif, CAGGA, present in a variety of genes expressed in
      the nervous system.

PMID- 8530497
TI  - Novel tricyclic inhibitors of farnesyl protein transferase. Biochemical
      characterization and inhibition of Ras modification in transfected Cos cells.
AB  - Ras protooncogenes encode 21-kDa membrane-associated guanine nucleotide-binding
      proteins, which play a critical role in control of cellular proliferation and
      differentiation. Oncogenic, activated forms of Ras proteins are associated with a
      broad range of human cancers. The elucidation of the post-translational
      modifications that occur at the carboxyl terminus of Ras and the demonstration
      that farnesylation of Ras by farnesyl protein transferase is essential for Ras
      induced cellular transformation has opened up a new and promising approach to the
      development of anti-Ras therapeutics. We report here a novel series of potent
      farnesyl protein transferase (FPT) inhibitors, represented by SCH 44342. This
      compound inhibits both rat brain and recombinant human FPT with an IC50 of
      approximately 250 nM, while it is only weakly active against rat brain
      geranylgeranyl protein transferase-1 (IC50 > 114 microM). FPT inhibition has been
      observed using both Ha-Ras protein and Ki-Ras-derived peptide substrates in two
      different assay formats. SCH 44342 and its analogs also inhibit farnesylation of
      Ras in Cos cells transiently expressing [Val12]Ha-Ras with IC50 values in the low
      micromolar range. At these concentrations they do not inhibit sterol biosynthesis
      or geranylgeranylation of protein. In addition, we observed that Cos cells
      undergo pronounced morphological changes upon overexpression of [Val12]activated
      forms of Ha-Ras containing COOH-terminal sequences allowing farnesylation (CVLS)
      or geranylgeranylation (CVLL) but not upon overexpression of activated Ras
      lacking the isoprenylated Cys (SVLS). Ras-induced morphological changes can be
      partially reverted with lovastatin. Importantly, SCH 44342 can block
      morphological changes induced by [Val12]Ha-Ras-CVLS but not [Val12]Ha-Ras-CVLL.
      Recently, a number of other FPT inhibitors have been reported. Most of the
      compounds reported to have cell-based activity are peptidomimetic analogs of the
      CAAX substrate. Our FPT inhibitors are novel in that although they compete with
      Ras protein in kinetic experiments they are entirely nonpeptidic in nature, they
      do not have oxidizable sulfhydryl functions, and they are active in cells at low
      micromolar concentrations.

PMID- 8530498
TI  - Constitutive and cytokine-induced expression of the melanoma growth stimulatory
      activity/GRO alpha gene requires both NF-kappa B and novel constitutive factors.
AB  - Melanoma growth stimulatory activity (MGSA)/growth regulated (GRO) and
      interleukin-8 (IL-8) are highly related chemokines that have a causal role in
      melanoma progression. Expression of these chemokines is similar in that both
      require the NF-kappa B element and additional regions such as the CAAT/enhancer
      binding protein (C/EBP) element of the IL-8 promoter. The constitutive and
      cytokine IL-1-induced promoter activity of the chemokine MGSA/GRO alpha in normal
      retinal pigment epithelial and the Hs294T melanoma cells is partially regulated
      through the NF-kappa B element, which binds both NF-kappa B p50 and RelA (NF
      kappa B p65) homodimers and heterodimers. Mutational analysis of the MGSA/GRO
      alpha promoter reveals that, in addition to the NF-kappa B element, the immediate
      upstream region (IUR) is necessary for basal expression in retinal pigment
      epithelial and Hs294T cells. Gel mobility shift and UV cross-linking analyses
      demonstrate that several constitutive DNA binding proteins interact with the IUR.
      Although this region has sequence similarity to the several transcription factor
      elements including C/EBP, the IUR includes sequences that have no similarity to
      previously identified enhancer regions. Furthermore, RelA transactivates through
      either the NF-kappa B element or the IUR, suggesting a putative interaction
      between NF-kappa B and this novel complex.

PMID- 8530499
TI  - Localization of the site on the complement component C1q required for the
      stimulation of neutrophil superoxide production.
AB  - C1q, the recognition subunit of the classical complement pathway, interacts with
      specific cell surface molecules via its collagen-like region (C1q-CLR). This
      binding of C1q to neutrophils triggers the generation of toxic oxygen species. To
      identify the site on C1q that interacts with the neutrophil C1q receptor, C1q was
      isolated, digested with pepsin to produce C1q-CLR, and further cleaved with
      either trypsin or endoproteinase Lys-C. The resulting fragments were separated by
      gel filtration chromatography and analyzed functionally (activation of the
      respiratory burst in neutrophils) and structurally. Cleavage of C1q-CLR with
      endoproteinase Lys-C did not alter its ability to trigger neutrophil superoxide
      production. However, when C1q-CLR was incubated with trypsin under conditions
      permitting optimal cleavage, the ability of C1q-CLR to stimulate superoxide
      production in neutrophils was completely abrogated. Fractionation of the digests
      obtained with the two enzymes and identification by amino acid sequencing
      permitted localization of the receptor interaction site to a specific region of
      the C1q-CLR. Circular dichroism analyses demonstrated that cleavage by trypsin
      does not denature the remaining uncleaved collagen-like structure, suggesting
      that after trypsin treatment, the loss of activity was not due to a loss of
      secondary structure of the molecule. However, irreversible heat denaturation of
      C1q-CLR also abrogated all activity. Thus, a specific conformation conferred by
      the collagen triple helix constitutes the functional receptor interaction site.
      These data should direct the design of future specific therapeutic reagents to
      selectively modulate this response.

PMID- 8530500
TI  - Interaction between G proteins and tyrosine kinases upon T cell receptor.CD3
      mediated signaling.
AB  - Engagement of the T cell receptor (TCR).CD3 complex results in the induction of
      multiple intracellular events, with protein tyrosine kinases playing a pivotal
      role in their initiation. Biochemical studies also exist suggesting the
      involvement of heterotrimeric GTP-binding proteins (G proteins); however, the
      functional consequence of this participation in TCR.CD3-mediated signaling is
      unresolved. Here, we report TCR.CD3-mediated guanine nucleotide exchange among
      the 42-kDa G protein alpha subunits of the G alpha q/11 family, their physical
      association with CD3 epsilon, and the G alpha 11-dependent activation of
      phospholipase C beta. Protein tyrosine kinase inhibitors, however, abrogate
      TCR.CD3-mediated G protein activation. Quite interesting is the observation that
      cells transfected with a function-deficient mutant of G alpha 11 display
      diminished tyrosine phosphorylation of TCR.CD3 zeta and epsilon chains, as well
      as ZAP-70, upon anti-CD3 antibody triggering. These data indicate the involvement
      of the G alpha q/11 family in TCR.CD3 signaling at a step proximal to the
      receptor and suggest a reciprocal regulation between tyrosine kinases and G
      proteins in T cells.

PMID- 8530501
TI  - Fibroblast growth factor receptors (FGFRs) localize in different cellular
      compartments. A splice variant of FGFR-3 localizes to the nucleus.
AB  - We have raised specific antibodies to the second immunoglobulin-like domain of
      fibroblast growth factor receptors (FGFRs) and used these to investigate the
      expression and subcellular localization of FGFR-1, -2, -3, and -4 in breast
      epithelial cells. All four receptors classes could be detected in breast cell
      lines; however, FGFR-4 and FGFR-2 appeared to be expressed at a higher level in
      breast cancer cell lines than in normal epithelial cells. Surprisingly, FGFR-3
      localized in the cell nucleus by immunofluorescence. A second antibody to a
      separate epitope confirmed this finding and showed that the form of FGFR-3
      present must contain an intact kinase domain as well as the growth factor binding
      domain. Western analysis of fractionated cells revealed the presence of two forms
      of FGFR-3 of 135 and 110 kDa. The 110-kDa form was predominantly found in the
      nucleus, whereas the 135 kDa form was sometimes found in the nucleus. RT-PCR
      analysis of FGFR-3 mRNA showed the presence of a splice variant in which exons 7
      and 8 are deleted. This results in the translation of FGFR-3 missing the
      transmembrane domain but with an intact kinase domain, which could be a soluble,
      intracellular receptor. Transfection experiments showed that FGFR-3 containing
      this deletion and no signal peptide gave an identical nuclear staining pattern to
      that seen in breast epithelial cells. We conclude that two forms of FGFR-3 are
      present in breast epithelial cells; a full-length 135-kDa receptor, which has a
      conventional membrane localization, and a novel soluble form of 110 kDa.

PMID- 8530502
TI  - Thyroid hormones stabilize acetylcholinesterase mRNA in neuro-2A cells that
      overexpress the beta 1 thyroid receptor.
AB  - We investigated the intracellular events involved in the 3,3',5-triiodo-L
      thyronine (T3)-induced accumulation in acetylcholinesterase (AChE) activity in
      neuroblastoma cells (neuro-2a) that overexpress the human thyroid receptor beta 1
      (hTR beta 1). Treatment of these cells with T3 increased AChE activity and its
      mRNAs after a lag period of 24-48 h, and these levels increased through
      stabilization of the transcripts by T3. T3 had no effect on the transcriptional
      rate or processing of AChE transcripts. The protein kinase inhibitor H7 inhibited
      T3-induced accumulation in AChE activity and its mRNAs, whereas okadaic acid (a
      potent inhibitor of phosphatases 1 and 2A) potentiated the effect of T3. Okadaic
      acid and H7 have no effect on the binding of hTR beta 1 to T3 or the
      transcriptional rate of the AChE gene. Finally, treatment of cells with T3
      stimulated cytosolic serine/threonine, but not tyrosine kinase, activities. The
      time course analysis reveals that the increase in serine/threonine activity
      precedes the effect of T3 on AChE mRNAs. These results suggest that activation of
      a serine/threonine protein kinase pathway might be a link between nuclear thyroid
      hormone receptor activation and stabilization of AChE mRNA.

PMID- 8530503
TI  - ARP is a plasma membrane-associated Ras-related GTPase with remote similarity to
      the family of ADP-ribosylation factors.
AB  - The human and rat homologues of a novel Ras-related GTPase with unique structural
      features were cloned by polymerase chain reaction amplification and cDNA library
      screening. Their deduced amino acid sequences are highly homologous (97%
      identical amino acids; 88.3% identical nucleotides within the coding region) and
      comprise all six of the conserved motifs presumably involved in GTP binding.
      Because the sequences exhibit some similarity with members of the ADP
      ribosylation factor (ARF) family (33% identity with ADP-ribosylation factor 1
      (ARF1), 39% identity with ARF-like 3), the protein was designated ARP (ARF
      related protein). In contrast to all other members of the ARF family, ARP lacks
      the myristoylation site at position 2 and comprises an insertion of 8 amino acids
      in the region between PM1 and PM2. mRNA was found in most rat tissues examined
      (skeletal muscle, fat, liver, kidney, spleen, testis, adrenals, ovary, thymus,
      intestine, and lung). Western blot analysis with antiserum against recombinant
      ARP showed a 25-kDa protein in membranes from rat liver, testis, and kidney.
      Thus, the protein appears to be post-translationally modified for membrane
      anchoring. Unlike ARF, the ARP immunoreactivity was detected in plasma membranes
      but not in cytosol of fractionated 3T3-L1 cells. Recombinant ARP exhibited
      specific and saturable GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) binding
      and, unlike ARF isotypes, GTPase activity in the absence of tissue extracts or
      phospholipids. Thus, the structural and functional characteristics of ARP
      indicate that it represents a novel subtype of GTPases, presumably exerting a
      unique function and possibly involved in plasma membrane-related signaling
      events.

PMID- 8530504
TI  - Targeted disruption of H2B-V encoding a particular H2B histone variant causes
      changes in protein patterns on two-dimensional polyacrylamide gel electrophoresis
      in the DT40 chicken B cell line.
AB  - The chicken H2B gene family comprises eight members (H2B-I to H2B-VIII), which
      are all located in two major histone gene clusters. All of them have been shown
      to encode four different protein variants (classes I to IV). In the DT40 chicken
      B cell line, the H2B-V gene, encoding the class III H2B variant, constituted
      about 10% of the total intracellular mRNA from all the H2B genes. To study the
      nature of this particular variant in vivo, we generated heterozygous (H2B-V, +/-)
      and homozygous (H2B-V, -/-) DT40 mutants by targeted integration. The remaining
      H2B genes were shown to be expressed more in these mutants than in the wild-type
      cell lines. The growth rate of DT40 cells was unchanged in the absence of the H2B
      V gene. Two-dimensional polyacrylamide gel electrophoresis showed that the
      protein patterns were, on the whole, similar between the wild-type and homozygous
      cell lines. However, within this constant background, some cellular proteins
      disappeared or decreased quantitatively in the homozygous mutants, and several
      other proteins increased or newly appeared. These results suggest that the class
      III H2B variant participates negatively or positively in regulation of the
      expression of particular genes that encode the proteins that vary in DT40 cells.
      This type of regulation is possibly mediated through alterations in nucleosome
      structure over the restricted regions involving the putative genes of the DT40
      genome.

PMID- 8530505
TI  - An essential aspartic acid at each of two allosteric cGMP-binding sites of a cGMP
      specific phosphodiesterase.
AB  - The amino acid sequences of all known cGMP-binding phosphodiesterases (PDEs)
      contain internally homologous repeats (a and b) that are 80-90 residues in length
      and are arranged in tandem within the putative cGMP-binding domains. In the
      bovine lung cGMP-binding, cGMP-specific PDE (cGB-PDE or PDE5A), these repeats
      span residues 228-311 (a) and 410-500 (b). An aspartic acid (residue 289 or 478)
      that is invariant in repeats a and b of all known cGMP-binding PDEs was changed
      to alanine by site-directed mutagenesis of cGB-PDE, and wild type (WT) and mutant
      cGB-PDEs were expressed in COS-7 cells. Purified bovine lung cGB-PDE (native) and
      WT cGB-PDE displayed identical cGMP-binding kinetics, with approximately 1.8
      microM cGMP required for half-maximal saturation. The D289A mutant showed
      decreased affinity for cGMP (Kd > 10 microM) and the D478A mutant showed
      increased affinity for cGMP (Kd approximately 0.5 microM) as compared to WT and
      native cGB-PDE. WT and native cGB-PDE displayed an identical curvilinear profile
      of cGMP dissociation which was consistent with the presence of distinct slowly
      dissociating (koff = 0.26 h-1) and rapidly dissociating (koff = 1.00 h-1) sites
      of cGMP binding. In contrast, the D289A mutant displayed a single koff = 1.24 h
      1, which was similar to the calculated koff for the fast site of WT and native
      cGB-PDE, and the D478A mutant displayed a single koff = 0.29 h-1, which was
      similar to that calculated for the slow site of WT and native cGB-PDE. These
      results were consistent with the loss of a slow cGMP-binding site in repeat a of
      the D289A mutant cGB-PDE, and the loss of a fast site in repeat b of the D478A
      mutant, suggesting that cGB-PDE possesses two distinct cGMP-binding sites located
      at repeats a and b, with the invariant aspartic acid being crucial for
      interaction with cGMP at each site.

PMID- 8530506
TI  - Translocation of cytosol of exogenous, CAAX-tagged acidic fibroblast growth
      factor.
AB  - Acidic fibroblast growth factor (aFGF) added externally to cells has been
      proposed to enter the nucleus and stimulate DNA synthesis, but it has remained
      controversial whether or not exogenous aFGF has the capability of crossing
      cellular membranes. To test this, a novel principle to study translocation of
      proteins to the cytosol was developed by fusing a C-terminal farnesylation
      signal, a CAAX tag (C = Cys, A = an aliphatic amino acid, and X = any amino
      acid), onto aFGF. Farnesylation is only known to occur in the cytosol and
      possibly in the nucleus. When incubated with NIH3T3 cells overnight, about one
      third of the cell-associated, CAAX-tagged growth factor was farnesylated,
      indicating that efficient translocation had taken place. Binding to specific FGF
      receptors was required for translocation to occur. Part of the farnesylated
      growth factor was found in the nuclear fraction. The data indicate that CAAX
      tagged aFGF added externally to cells is able to cross cellular membranes and
      enter the cytosol and the nucleus.

PMID- 8530507
TI  - Cell type-specific modulation of cell growth by transforming growth factor beta 1
      does not correlate with mitogen-activated protein kinase activation.
AB  - Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional cytokine that
      positively or negatively regulates the proliferation of various types of cells.
      In this study we have examined whether or not the activation of the mitogen
      activated protein (MAP) kinases is involved in the transduction of cell growth
      modulation signals of TGF-beta 1, as MAP kinase activity is known to be closely
      associated with cell cycle progression. Although TGF-beta 1 stimulated the growth
      of quiescent Balb 3T3 and Swiss 3T3 cells, it failed to detectably stimulate the
      tyrosine phosphorylation and activation of the 41- and 43-kDa MAP kinases at any
      time point up to the reinitiation of DNA replication. TGF-beta 1 also failed to
      stimulate the expression of the c-fos gene. Furthermore, TGF-beta 1
      synergistically enhanced the mitogenic action of epidermal growth factor (EGF)
      without affecting EGF-induced MAP kinase activation in these fibroblasts, and it
      inhibited the EGF-stimulated proliferation of mouse keratinocytes (PAM212)
      without inhibiting EGF-induced MAP kinase activation. Thus, the ability of TGF
      beta 1 to modulate cell proliferation is apparently not associated with the
      activation of MAP kinases. In this respect, TGF-beta 1 is clearly distinct from
      the majority, if not all, of peptide growth factors, such as platelet-derived
      growth factor and EGF, whose ability to modulate cell proliferation is closely
      associated with the activation of MAP kinases. These results also suggest that
      the activation of MAP kinases is not an absolute requirement for growth factor
      stimulated mitogenesis.

PMID- 8530508
TI  - Preferential stimulation of human progesterone receptor B expression by estrogen
      in T-47D human breast cancer cells.
AB  - Human progesterone receptor (PR) expression is controlled by two promoter regions
      giving rise to transcripts encoding PR A and B proteins. It is unknown whether
      estrogen and progesterone, the major physiological modulators of PR expression,
      exert their effects equally on the PR promoters. The aim of this study was to
      analyze estrogen and progestin effects on PR promoters, PR-encoding transcripts,
      and PR A and B proteins in T-47D human breast cancer cells. The progestin ORG
      2058 caused a prolonged decrease in transcription of the PR gene and also
      abrogated estrogen stimulation of PR transcription. Estradiol (E2) treatment
      increased the activity of the B but not the A promoter transfected into T-47D
      cells. ORG 2058 had no effect on the basal or E2-stimulated activity of either
      promoter. E2 caused a preferential increase in transcripts derived from promoter
      B, whereas progestins decreased the levels of all PR transcripts. E2
      preferentially increased the concentration of the PR B protein and caused a
      decrease in the PR A/B ratio. This demonstration that estrogen and progestin
      independently control the synthesis of transcripts arising from the PR promoters
      and that estrogen alters the cellular PR A/B ratio provides possible mechanisms
      underlying the cell and tissue specificity of PR regulation.

PMID- 8530509
TI  - Role of ceramide in cellular senescence.
AB  - Recently the sphingomyelin cycle, involving the hydrolysis of membrane
      sphingomyelin by an activated sphingomyelinase to generate ceramide, has emerged
      as a key pathway in cell differentiation and apoptosis in leukemic and other cell
      types. Here we investigate a role for this pathway in the senescence of WI-38
      human diploid fibroblasts (HDF). We found that endogenous levels of ceramide
      increased considerably (4-fold) and specifically (compared with other lipids) as
      cells entered the senescent phase. Investigation of the mechanism of increased
      ceramide led to the discovery that neutral sphingomyelinase activity is elevated
      8-10 fold in senescent cells. There were no changes in sphingomyelinase activity
      or ceramide levels as HDF entered quiescence following serum withdrawal or
      contact inhibition. Thus, the activation of the sphingomyelinase/ceramide pathway
      in HDF is due to senescence and supports the hypotheses that senescence
      represents a distinct program of cell development that can be differentiated from
      quiescence. Additional studies disclosed the ability of ceramide to induce a
      senescent phenotype. Thus, when exogenous ceramide (15 microM) was administered
      to young WI-38 HDF, it produced endogenous levels comparable to those observed in
      senescent cells (as determined by metabolic labeling studies). Ceramide
      concentrations of 10-15 microM inhibited the growth of young HDF and induced a
      senescent phenotype by its ability to inhibit DNA synthesis and mitogenesis.
      These concentrations of ceramide also induced retinoblastoma dephosphorylation
      and inhibited serum-induced AP-1 activation in young HDF, thus recapitulating
      basic biochemical and molecular changes of senescence. Sphingomyelinase and
      ceramide may thus be implicated as mediators of cellular senescence.

PMID- 8530510
TI  - Human endonucleolytic incision of DNA 3' and 5' to a site-directed psoralen
      monoadduct and interstrand cross-link.
AB  - Human chromatin-associated protein extracts were examined for endonucleolytic
      activity on a defined 132-base pair DNA substrate containing a single, site
      specific 4,5'-8-trimethylpsoralen plus long wavelength ultraviolet light-induced
      furan side or pyrone side monoadduct or interstrand cross-link. These extracts
      produced incisions on both the 3' and 5' sides of each of these lesions. The
      distance between the 3' and 5' incisions at sites of a furan side monoadduct or
      cross-link was 9 nucleotides, and at sites of a pyrone side monoadduct or cross
      link it was 17 nucleotides. Incisions on the 3' side of both types of furan side
      and pyrone side adducts were similar and were either at the fourth or fifth
      phosphodiester bond from the adducted thymine, depending upon the adduct.
      However, greater differences were observed between sites of 5' incision. This
      incision occurred at the fifth and sixth phosphodiester bonds from the adducted
      thymine at sites of furan side monoadducts and cross-links, respectively, and at
      the 13th and 14th phosphodiester bonds at sites of pyrone side monoadducts and
      cross-links, respectively. Thus, direct analysis of sites of endonucleolytic
      incision reveals that the location of sites of incision on TMP-adducted
      substrates depends upon the type of adduct present.

PMID- 8530511
TI  - Dominant-negative mutants of Grb2 induced reversal of the transformed phenotypes
      caused by the point mutation-activated rat HER-2/Neu.
AB  - To clarify the role of the Shc-Grb2-Sos trimer in the oncogenic signaling of the
      point mutation-activated HER-2/neu receptor tyrosine kinase (named p185), we
      interfered with the protein-protein interactions in the Shc.Grb2.Sos complex by
      introducing Grb2 mutants with deletions in either amino- (delta N-Grb2) or
      carboxyl-(delta C-Grb2) terminal SH3 domains into B104-1-1 cells derived from
      NIH3T3 cells expressing the point mutation-activated HER-2/neu. We found that the
      transformed phenotypes of the B104-1-1 cells were largely reversed by the delta N
      Grb2. The effect of the delta C-Grb2 was much weaker. Biochemical analysis showed
      that the delta N-Grb2 was able to associate Shc but not p185 or Sos, while the
      delta C-Grb2 bound to Shc, p185, and Sos. The p185-mediated Ras activation was
      severely inhibited by the delta N-Grb2 but not the delta C-Grb2. Taken together,
      these data demonstrate that interruption of the interaction between Shc and the
      endogenous Grb2 by the delta N-Grb2 impairs the oncogenic signaling of the
      activated p185, indicating that (i) the delta N-Grb2 functions as a strong
      dominant-negative mutant, and (ii) Shc/Grb2/Sos pathway plays a major role in
      mediating the oncogenic signal of the activated p185. Unlike the delta N-Grb2,
      delta C-Grb2 appears to be a relatively weak dominant-negative mutant, probably
      due to its ability to largely fulfill the biological functions of the wild-type
      Grb2.

PMID- 8530513
TI  - Internalization of vitronectin-thrombin-antithrombin complex by endothelial cells
      leads to deposition of the complex into the subendothelial matrix.
AB  - Internalization of the ternary vitronectin-thrombin-antithrombin (VN-TAT) complex
      by human umbilical vein endothelial cells was investigated. Radiolabeled VN-TAT
      was bound to the cell surface at 4 degrees C, and internalization was initiated
      by increasing the temperature to 37 degrees C. After 30 min about half of the VN
      TAT complex disappeared from the cell surface and accumulated in the
      subendothelial matrix. Translocation of VN-TAT complex from the luminal to the
      basolateral side was confirmed by electron microscopic evaluation of cross
      sections of endothelial cells incubated with gold-conjugated VN-TAT complex.
      Furthermore, cells cultured in VN-TAT deficient serum, incubated with purified VN
      TAT, and subsequently assayed for fluorescent staining using a monoclonal
      antibody directed against thrombin-modified antithrombin and a polyclonal
      antibody against vitronectin showed co-localization of both antibodies in
      punctates. Punctates were randomly distributed in both the xy and xz plane of
      endothelial cells as evidenced by confocal laser scanning microscopy.
      Trichloroacetic acid precipitation and SDS-polyacrylamide gel electrophoresis
      showed that VN-TAT was not degraded during translocation and inhibition of the
      microfilament system reduced release of VN-TAT to the matrix, indicating that
      transcytosis was responsible for translocation. These findings emphasize that VN
      TAT complex is taken up by endothelial cells, not only leading to the removal of
      inactivated thrombin from the circulation but also to deposition of VN into the
      subendothelial matrix.

PMID- 8530512
TI  - Genomic cloning, characterization, and functional analysis of the major surface
      adhesin WI-1 on Blastomyces dermatitidis yeasts.
AB  - WI-1 is a 120-kDa surface protein adhesin on Blastomyces dermatitidis yeasts that
      binds CD18 and CD14 receptors on human macrophages. We isolated and analyzed a
      clone of genomic WI-1 to characterize this key adherence mechanism of the yeast.
      The 9.3-kilobase insert contains an open reading frame of 3438 nucleotides and no
      introns. The amino acid sequence of native WI-1 matches the deduced sequence of
      genomic WI-1 at positions 757-769, 901-913, and 1119-1138, demonstrating the
      cloned gene is authentic WI-1. The complete coding sequence has 30 highly
      conserved repeats of 24 amino acids arrayed in tandem in two noncontiguous
      regions of the protein. The repeat sequence is homologous to the Yersiniae
      adhesin invasin, the C terminus displays an epidermal growth factor-like domain,
      and the N terminus has a short hydrophobic sequence that may be a membrane
      spanning domain. The tandem repeats are predicted to be at the exposed surface of
      the protein, thereby explaining the adhesive properties of WI-1. The WI-1
      promoter contains a CAAT box (nucleotide positions 2287-2290), TATA box (2380
      2385), and CT motif (2399-2508). Transcription is initiated within the CT motif
      at nucleotide 2431. A 5.5-kilobase subclone containing the full coding sequence
      of WI-1 was expressed as a histidine-tagged fusion protein in Escherichia coli.
      Recombinant WI-1 has the expected molecular mass of 120 kDa, is strongly
      recognized in Western blots by rabbit anti-WI-1 antiserum, and binds human
      macrophage receptors in the same manner as native WI-1. This work clarifies a key
      adherence mechanism of B. dermatitidis and will permit further analysis of WI-1
      mediated attachment to host cells, receptors, and extracellular matrix.

PMID- 8530514
TI  - Native and activated forms of alpha 2-macroglobulin increase expression of
      platelet-derived growth factor alpha-receptor in vascular smooth muscle cells.
      Evidence for autocrine transforming growth factor-beta activity.
AB  - Cellular response to platelet-derived growth factor AA (PDGF-AA) is mediated
      exclusively by the PDGF alpha-receptor. Vascular smooth muscle cells (VSMCs) in
      culture typically express very low levels of alpha-receptor. In this study, we
      demonstrate that the proteinase inhibitor and cytokine carrier alpha 2
      macroglobulin (alpha 2M) increases rat VSMC PDGF alpha-receptor expression. PDGF
      alpha-receptor mRNA levels increased 3-fold by 6 h and were sustained at that
      level through 24 h in VSMCs treated with 280 nM methylamine-modified alpha 2M
      (alpha 2M-MA), a form of activated alpha 2M. PDGF beta-receptor mRNA levels were
      unchanged in the same time period. In 125I-PDGF-AA binding experiments, treatment
      of VSMCs with alpha 2M-MA increased the maximum binding capacity (Bmax) from 1.9
      to 9.2 fmol/mg of cell protein without affecting binding affinity (KD
      approximately 80 pM). alpha 2M-MA also increased the VSMC response to PDGF-AA as
      determined by tyrosine phosphorylation of a 170-kDa band, corresponding in mass
      to the PDGF alpha-receptor. The native form of alpha 2M was comparable to alpha
      2M-MA in its ability to increase PDGF-AA binding to VSMCs and tyrosine
      phosphorylation of the 170-kDa band. Recombinant and proteolytic alpha 2M
      derivatives were used to demonstrate that alpha 2M increases PDGF alpha-receptor
      expression by binding VSMC-secreted cytokine(s) and interrupting an autocrine
      loop that ordinarily suppresses alpha-receptor expression in these cells.
      Transforming growth factor-beta-neutralizing antibody mimicked the activity of
      alpha 2M, increasing the binding capacity of VSMCs for PDGF-AA. This study
      demonstrates that VSMC PDGF alpha-receptor expression and responsiveness to PDGF
      AA are regulated by autocrine transforming growth factor-beta activity,
      potentially other autocrine growth factors, and alpha 2M.

PMID- 8530515
TI  - Calcium-mediated translocation of cytosolic phospholipase A2 to the nuclear
      envelope and endoplasmic reticulum.
AB  - Cytosolic phospholipase A2 (cPLA2) is activated by a wide variety of stimuli to
      release arachidonic acid, the precursor of the potent inflammatory mediators
      prostaglandin and leukotriene. Specifically, cPLA2 releases arachidonic acid in
      response to agents that increase intracellular Ca2+. In vitro data have suggested
      that these agents induce a translocation of cPLA2 from the cytosol to the cell
      membrane, where its substrate is localized. Here, we use immunofluorescence to
      visualize the translocation of cPLA2 to distinct cellular membranes. In Chinese
      hamster ovary cells that stably overexpress cPLA2, this enzyme translocates to
      the nuclear envelope upon stimulation with the calcium ionophore A23187. The
      pattern of staining observed in the cytoplasm suggests that cPLA2 also
      translocates to the endoplasmic reticulum. We find no evidence for cPLA2
      localization to the plasma membrane. Translocation of cPLA2 is dependent on the
      calcium-dependent phospholipid binding domain, as a calcium-dependent
      phospholipid binding deletion mutant of cPLA2 (delta CII) fails to translocate in
      response to Ca2+. In contrast, cPLA2 mutated at Ser-505, the site of mitogen
      activated protein kinase phosphorylation, translocates normally. This
      observation, combined with the observed phosphorylation of delta CII, establishes
      that translocation and phosphorylation function independently to regulate cPLA2.
      The effect of these mutations on cPLA2 translocation was confirmed by subcellular
      fractionation. Each of these mutations abolished the ability of cPLA2 to release
      arachidonic acid, establishing that cPLA2-mediated arachidonic acid release is
      strongly dependent on both phosphorylation and translocation. These data help to
      clarify the mechanisms by which cPLA2 is regulated in intact cells and establish
      the nuclear envelope and endoplasmic reticulum as primary sites for the
      liberation of arachidonic acid in the cell.

PMID- 8530516
TI  - A fraction enriched in a novel glucocorticoid receptor-interacting protein
      stimulates receptor-dependent transcription in vitro.
AB  - Glucocorticoids influence numerous cell functions by regulating gene activity.
      The glucocorticoid receptor (GR) is a ligand-activated transcription factor and,
      like any other transcription factor, does not modulate gene activity just by
      binding to DNA. Interaction with other proteins is probably required to enhance
      the establishment of a functional transcription initiation complex. To identify
      such proteins, we analyzed the in vitro interaction of the glucocorticoid
      receptor bound to a double glucocorticoid response element with nuclear proteins
      and describe here three interacting proteins with different molecular weights.
      One of them, which we named GRIP 170 (GR-interacting protein), was purified and
      microsequenced, and it turned out to be an unknown protein. When tested in a cell
      free transcription assay, the fraction highly enriched for GRIP 170 does not
      influence basal promoter activity but does enhance GR induction.

PMID- 8530517
TI  - LLC-PK1 cell growth is repressed by WT1 inhibition of G-protein alpha i-2
      protooncogene transcription.
AB  - The temporal expression of the early growth response gene (EGR-1) is one
      molecular mechanism for both maximal activation of the G alpha i-2 gene and
      accelerated growth in mitotically active predifferentiated LLC-PK1 renal cells.
      These events are dependent on an enhancer area in the 5'-flanking region of the G
      alpha i-2 gene that contains an EGR-1 motif (5'-CGCCCCCGC-3'). However,
      acquisition of the polarized phenotype in LLC-PK1 cells is accompanied by loss of
      EGR-1 expression and occupancy of the EGR-1 site by nuclear binding proteins
      other than EGR-1. We now demonstrate that one of these binding proteins is the
      Wilms' tumor suppressor (WT1). Furthermore, the temporal expression of WT1 in LLC
      PK1 cells acquiring the polarized phenotype represses both G alpha i-2 gene
      activation and growth in these cells. These findings suggest the existence of
      differentiation-induced pathways in LLC-PK1 cells that alternatively abrogates
      EGR-1 and promotes WT1 gene expression, thereby modulating a target protooncogene
      G alpha i-2 that is participatory for growth and differentiation in renal cells.
      These studies emphasize the usefulness of the LLC-PK1 renal cell as a model to
      elucidate normal programs of genetic differentiation in which WT1 participates.

PMID- 8530518
TI  - Enhancement of HL-60 differentiation by a new class of retinoids with selective
      activity on retinoid X receptor.
AB  - Cellular responsiveness to retinoic acid and its metabolites is conferred through
      two distinct families of receptors: the retinoic acid receptors (RARs) and the
      retinoid X receptors (RXRs). Herein, we report on the identification and
      characterization of several conformationally restricted retinoids, which
      selectively bind and activate RX receptors. Under the influence of retinoids, HL
      60 myelocytic leukemia cells differentiate into granulocytes. This effect is
      mediated by RAR alpha, as has been demonstrated through the use of a selective
      RAR alpha antagonist (Apfel, C., Bauer, F., Crettaz, M., Forni, L., Kamber, M.,
      Kaufmann, F., LeMotte, P., Pirson, W., and Klaus, M. (1992) Proc. Natl. Acad.
      Sci. U.S.A. 89, 7129-7133). Here, we show that conformationally restricted RXR
      specific retinoids, at doses that are per se inactive, are able to potentiate by
      up to one order of magnitude the pro-differentiating effects of all-trans
      retinoic acid and an RAR alpha-selective synthetic retinoid. We also present
      evidence that these RXR-selective ligands are able to bind to a DNA RXR.RAR
      heterodimer complex. This finding demonstrates that agonists for RARs and RXRs
      can synergistically promote HL-60 differentiation, which could be mediated
      through a heterodimer of these receptors.

PMID- 8530519
TI  - Phosphorylation of both serine residues in cardiac troponin I is required to
      decrease the Ca2+ affinity of cardiac troponin C.
AB  - The phosphorylation of cardiac muscle troponin I (CTnI) at two adjacent N
      terminal serine residues by cAMP-dependent protein kinase (PKA) has been
      implicated in the inotropic response of the heart to beta-agonists.
      Phosphorylation of these residues has been shown to reduce the Ca2+ affinity of
      the single Ca(2+)-specific regulatory site of cardiac troponin C (CTnC) and to
      increase the rate of Ca2+ dissociation from this site (Robertson, S. P., Johnson,
      J. D., Holroyde, M. J., Kranias, E. G., Potter, J. D., and Solaro, R. J. (1982)
      J. Biol. Chem. 257, 260-263). Recent studies (Zhang, R., Zhao, J., and Potter, J.
      D. (1995) Circ. Res. 76, 1028-1035) have correlated this increase in Ca2+
      dissociation with a reduced Ca2+ sensitivity of force development and a faster
      rate of cardiac muscle relaxation in a PKA phosphorylated skinned cardiac muscle
      preparation. To further determine the role of the two PKA phosphorylation sites
      in mouse CTnI (serine 22 and 23), serine 22 or 23, or both were mutated to
      alanine. The wild type and the mutated CTnIs were expressed in Escherichia coli
      and purified. Using these mutants, it was found that serine 23 was phosphorylated
      more rapidly than serine 22 and that both serines are required to be
      phosphorylated in order to observe the characteristic reduction in the Ca2+
      sensitivity of force development seen in a skinned cardiac muscle preparation.
      The latter result confirms that PKA phosphorylation of CTnI, and not other
      proteins, is responsible for this change in Ca2+ sensitivity. The results also
      suggest that one of the serines (23) may be constitutively phosphorylated and
      that serine 22 may be functionally more important.

PMID- 8530520
TI  - Succinate dehydrogenase b mRNA of Drosophila melanogaster has a functional iron
      responsive element in its 5'-untranslated region.
AB  - Iron-responsive elements (IREs) are cis-acting mRNA stem-loop structures that
      specifically bind cytoplasmic iron regulatory proteins (IRPs). IRP-IRE
      interactions mediate the coordinate post-transcriptional regulation of key
      proteins in iron metabolism, such as ferritin, transferrin receptor, and
      erythroid 5-aminolevulinic acid synthase. Depending on whether the IRE is located
      in the 5'- or 3'-untranslated region (UTR), binding of IRP will inhibit mRNA
      translation or degradation, respectively. Here we describe a new IRE in the 5'
      UTR of succinate dehydrogenase subunit b (SDHb) mRNA of Drosophila melanogaster.
      The SDHb IRE binds in vitro to vertebrate and insect IRPs with a high affinity
      equal to that of human ferritin H chain IRE. Under conditions of iron
      deprivation, SDHb mRNA of Drosophila SL-2 cells shifts to a non-polysome-bound
      pool. Moreover, translation of a human growth hormone mRNA with the SDHb IRE in
      its 5'-UTR is iron-dependent in stably transfected L cells. We conclude that the
      SDHb IRE mediates translational inhibition both in insect and vertebrate cells.
      This constitutes the first identification of a functional IRE in insects.
      Furthermore, Drosophila SDHb represents the second example, after porcine
      mitochondrial aconitase, of an enzyme of the citric acid cycle whose mRNA
      possesses all necessary features for translational regulation by cellular iron
      levels.

PMID- 8530521
TI  - Purification, primary structure, and immunological characterization of the 26-kDa
      calsequestrin binding protein (junctin) from cardiac junctional sarcoplasmic
      reticulum.
AB  - Previously we identified a protein of apparent M(r) = 26,000 as the major
      calsequestrin binding protein in junctional sarcoplasmic reticulum vesicles
      isolated from cardiac and skeletal muscle (Mitchell, R. D., Simmerman, H. K. B.,
      and Jones, L. R. (1988) J. Biol. Chem. 263, 1376-1381). Here we describe the
      purification and primary structure of the 26-kDa calsequestrin binding protein.
      The protein was purified 164-fold from cardiac microsomes and shown by
      immunoblotting to be highly enriched in junctional membrane subfractions. It ran
      as a closely spaced doublet on SDS-polyacrylamide gel electrophoresis and bound
      125I-calsequestrin intensely. Cloning of the cDNA predicted a protein of 210
      amino acids containing a single transmembrane domain. The protein has a short N
      terminal region located in the cytoplasm, and the bulk of the molecule, which is
      highly charged and basic, projects into the sarcoplasmic reticulum lumen.
      Significant homologies were found with triadin and aspartyl beta-hydroxylase,
      suggesting that all three proteins are members of a family of single membrane
      spanning endoplasmic reticulum proteins. Immunocytochemical labeling localized
      the 26-kDa protein to junctional sarcoplasmic reticulum in cardiac and skeletal
      muscle. The same gene product was expressed in these two tissues. The
      calsequestrin binding activity of the 26-kDa protein combined with its
      codistribution with calsequestrin and ryanodine receptors strongly suggests that
      the protein plays an important role in the organization and/or function of the
      Ca2+ release complex. Because the 26-kDa calsequestrin binding protein is an
      integral component of the junctional sarcoplasmic reticulum membrane in cardiac
      and skeletal muscle, we have named it Junctin.

PMID- 8530522
TI  - Pre- and post-translational regulation of lysyl oxidase by transforming growth
      factor-beta 1 in osteoblastic MC3T3-E1 cells.
AB  - The final enzymatic step required for collagen cross-linking is the extracellular
      oxidative deamination of peptidyl-lysine and -hydroxylysine residues by lysyl
      oxidase. A cross-linked collagenous extracellular matrix is required for bone
      formation. The goals of this study were to compare the transforming growth factor
      (TGF)-beta 1 regulation of lysyl oxidase enzyme activity and steady state mRNA
      levels to changes in COL1A1 mRNA levels in MC3T3-E1 osteoblastic cells. TGF-beta
      1 increased steady state lysyl oxidase and COL1A1 mRNA levels in a dose- and time
      dependent manner. The increase in lysyl oxidase mRNA levels was transient,
      peaking at 12 h and 8.8 times controls in cells treated with 400 pM TGF-beta 1.
      COL1A1 steady state mRNA levels increased maximally to 3.5-fold of controls.
      Development of increased lysyl oxidase enzyme activity was delayed and was of
      slightly lower magnitude than the increase in its mRNA levels. This suggested
      limiting post-translational processing of lysyl oxidase proenzyme. Pulse
      labeling/immunoprecipitation studies demonstrated slow proenzyme secretion and
      proteolytic processing. Development and application of an independent assay for
      lysyl oxidase proenzyme proteolytic processing activity verified its
      proportionately lower stimulation by 400 pM TGF-beta 1. Thus, lysyl oxidase
      regulation by TGF-beta 1 in osteoblastic cell cultures occurs at both pre- and
      post-translational levels. This regulation is consistent with increased
      production of a collagenous extracellular matrix.

PMID- 8530523
TI  - Dissociation of hexameric Escherichia coli inorganic pyrophosphatase into trimers
      on His-136-->Gln or His-140-->Gln substitution and its effect on enzyme catalytic
      properties.
AB  - Each of the five histidines in Escherichia coli inorganic pyrophosphatase (PPase)
      was replaced in turn by glutamine. Significant changes in protein structure and
      activity were observed in the H136Q and H140Q variants only. In contrast to wild
      type PPase, which is hexameric, these variants can be dissociated into trimers by
      dilution, as shown by analytical ultracentrifugation and cross-linking. Mg2+ and
      substrate stabilize the hexameric forms of both variants. The hexameric H136Q-
      and H140Q-PPases have the same binding affinities for magnesium ion as wild-type,
      but their hydrolytic activities under optimal conditions are, respectively, 225
      and 110% of wild-type PPase, and their synthetic activities, 340 and 140%. The
      increased activity of hexameric H136Q-PPase results from an increase in the rate
      constants governing most of the catalytic steps in both directions. Dissociation
      of the hexameric H136Q and H140Q variants into trimers does not affect the
      catalytic constants for PPi hydrolysis between pH 6 and 9 but drastically
      decreases their affinities for Mg2PPi and Mg2+. These results prove that His-136
      and His-140 are key residues in the dimer interface and show that hexamer
      formation improves the substrate binding characteristics of the active site.

PMID- 8530524
TI  - Comparative studies of human recombinant 74- and 54-kDa L-histidine
      decarboxylases.
AB  - We have expressed and characterized human recombinant 74-kDa (rHDC74) and 54-kDa
      (rHDC54) L-histidine decarboxylases (HDCs) in Sf9 cells. By immunoblot analysis,
      rHDC74 and rHDC54 were shown to be localized predominantly in the particulate and
      soluble fractions, respectively. rHDC74 exhibited histamine-synthesizing activity
      equivalent to that of rHDC54. The existence of 74- and 54-kDa HDCs was also
      confirmed in the particulate and supernatant fractions of the cell lysate,
      respectively, from the human basophilic leukemia cell line KU-812-F. The ratio of
      HDC activity to immunoreactivity was similar for the two forms of the enzyme. The
      specific activity of purified rHDC54 (1.12 mumol/mg/min) was comparable to those
      of HDCs from other mammalian tissues or cells. The purified rHDC54 was eluted as
      a monomer form from a Superdex-200 column; the molecular mass of the enzyme was
      approximately 54 kDa on SDS-polyacrylamide gel electrophoresis without 2
      mercaptoethanol. The HDC activity of rHDC54 significantly decreased on dialysis
      against buffer without pyridoxal 5'-phosphate; addition of pyridoxal 5'-phosphate
      to the dialysate readily increased in the enzyme activity to the original
      activity. Taken together, these results suggest that human HDC functions as both
      74- and 54-kDa forms having equivalent HDC activity, which are localized in the
      particulate and soluble fractions, respectively, and that the latter form
      exhibits its activity as a monomer form.

PMID- 8530525
TI  - The guanylyl cyclase-A receptor transduces an atrial natriuretic peptide/ATP
      activation signal in the absence of other proteins.
AB  - Attempts to activate partially purified preparations of the guanylyl cyclase-A
      (GC-A) receptor with atrial natriuretic peptide (ANP) have previously failed,
      leading to speculation that essential cofactors are lost during purification
      procedures. The receptor was modified to contain the FLAG epitope (DYKDDDDK),
      expressed in Sf9 cells, and purified to apparent homogeneity (4.3 mumol cyclic
      GMP formed/min/mg protein; 5.8 mmol 125I-ANP binding site/mg protein) by a
      combination of immunoaffinity, Q-Sepharose FF, and wheat germ agglutinin batch
      chromatography. High initial protein/detergent ratios, the presence of glycerol
      (40%), and the inclusion of protein phosphatase inhibitors in all buffers
      resulted in the purification of a receptor that continued to transduce the
      ANP/ATP activation signal. Both native and purified GC-A contained a single class
      of high affinity ANP binding sites (Kd = 60 pM) and an equivalent EC50 for ATP
      (0.3 mM). Positive cooperativity as a function of MnGTP was retained during
      purification. Thus, GC-A is capable of transducing a ligand binding signal in the
      absence of other proteins.

PMID- 8530526
TI  - Selective activation of c-Jun kinase mitogen-activated protein kinase by CD40 on
      human B cells.
AB  - The B cell surface antigen receptor, surface IgM (sIgM), is involved in B cell
      activation and proliferation. CD40 is involved in regulating IgE production and B
      cell survival. Cross-linking of B cell sIgM activates the Ras/Raf/p42erk2
      pathway. In contrast, ligation of CD40 by antibody or soluble gp39 (CD40 ligand)
      leads to activation of the c-Jun kinase (JNK)/stress-activated protein kinase
      pathway. JNK/stress-activated protein kinase activation correlated with the
      stimulation of MEK kinase activity. CD40 does not activate the p42erk2 pathway,
      and sIgM fails to regulate the JNK/stress-activated protein kinase pathway in B
      cells. Thus, two important cell surface receptors involved in controlling
      specific B cell response differentially regulate sequential protein kinase
      pathways involving different members of the mitogen-activated protein kinase
      family. Anti-CD40 also rescued B cell apoptosis induced by anti-IgM. CD40
      ligation did not affect the sIgM stimulation of p42erk2 activity. Conversely,
      sIgM ligation did not influence CD40 stimulation of JNK/stress-activated protein
      kinase. These results suggest that independent, parallel protein kinase response
      pathways are involved in the integration of sIgM and CD40 control of B cell
      phenotype and function.

PMID- 8530527
TI  - Receptors for interleukin (IL)-4 do not associate with the common gamma chain,
      and IL-4 induces the phosphorylation of JAK2 tyrosine kinase in human colon
      carcinoma cells.
AB  - We have previously reported on the expression of interleukin-4 receptors (IL-4R)
      on many human epithelial cancer cells; however, the binding characteristics,
      structure, function, and signal transduction through the IL-4R in cancer cells is
      not known. IL-4 binding characteristics were determined in human colon carcinoma
      cell lines by a 125I-IL-4 binding assay, which demonstrated that the HT-29 and
      WiDr colon cancer cell lines expressed high affinity IL-4R (Kd = 200 pM). Cross
      linking experiments revealed a major band of 140 kDa and a broad band at 70 kDa.
      While the common gamma chain of IL-2R is associated with IL-4R in immune cells
      and is similar in size to the 70-kDa protein, this chain was not expressed in
      these colon cancer cells. Interestingly, IL-13, which has many functions similar
      to IL-4, inhibited 125I-IL-4 binding to both the 140- and 70-kDa molecules. Next,
      we investigated the mechanism of IL-4-induced signal transduction in colon cancer
      cells. After stimulation with IL-4, a 170-kDa band was primarily phosphorylated
      within 1 min of exposure and was identified as insulin receptor substrate-1. In
      addition, by immunoprecipitation assay, three other phosphorylated bands were
      identified as JAK1, JAK2, and Tyk2 tyrosine kinases. The phosphorylation of JAK1
      and JAK2 was induced by IL-4 stimulation; however, Tyk2 was constitutively
      phosphorylated, and IL-4 treatment further augmented this phosphorylation. The
      kinetics and in vitro kinase assays demonstrated that JAK1, JAK2, and Tyk2 were
      phosphorylated within minutes and that JAK1 and JAK2 were activated after IL-4
      exposure. Contrary to observations in immune cells. JAK3 mRNA was neither
      detected in colon cancer cells nor did IL-4 treatment cause phosphorylation of
      JAK3. These data indicate that in colon carcinoma cells JAK1, JAK2, Tyk2, and
      insulin receptor substrate-1 are phosphorylated after IL-4 stimulation. In
      addition, as is the case in lymphoid cells, IL-4 activated and phosphorylated
      signal transducers and activators of transcription (IL-4-STAT or STAT-6) protein
      in both colon cancer cell lines. These results indicate that the IL-4R complex is
      composed of different subunits in different tissues and shares a component with
      the IL-13R complex. In addition, we demonstrate for the first time that like its
      family members (e.g. IL-3 and GM-CSF), IL-4 can phosphorylate and activate JAK-2
      kinase.

PMID- 8530528
TI  - Molecular mechanisms of bone resorption.
AB  - This review focuses on osteoclast ontogeny and function, emphasizing three
      aspects. We describe how a combination of laboratory models available to study
      the cell plus examination of the osteopetroses, a family of sclerotic diseases of
      the skeleton, have yielded major insights into osteoclast ontogeny and function.
      We proceed to describe the cell and molecular machinery enabling osteoclasts to
      resorb bone. The final, and most speculative, aspect of the review addresses
      possible mechanisms by which the osteoclast assumes its characteristic
      morphology, that of a polarized cell on bone. Since little direct information has
      been forthcoming as to how the osteoclast polarizes, we draw on other polarized
      cells. In particular, we examine the role of microtubules and members of the
      small GTPase family, the latter mediating polarized targeting of intracellular
      vesicles. In the case of the osteoclast, such vesicles probably represent the
      origin of the highly convoluted ruffled membrane, the cell's characteristic bone
      resorptive organ.

PMID- 8530529
TI  - Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with
      schizophrenic disorder.
AB  - As compared to normal people, the lymphocytes of patients with schizophrenia were
      found to have an impairment of ATP.Mg-dependent protein phosphatase activation.
      More importantly, the impaired protein phosphatase activation in the lymphocytes
      of schizophrenic patients could be consistently and completely restored to normal
      by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase
      FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase),
      indicating that the molecular mechanism for the impaired protein phosphatase
      activation in schizophrenic patients may be due to a functional loss of kinase
      FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase
      FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular
      activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of
      schizophrenic patients were greatly impared as compared to normal controls.
      Statistical analysis revealed that the lymphocytes isolated from 37 normal people
      contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4
      units/mg of cell protein, whereas the lymphocytes of 48 patients with
      schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels
      of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3
      alpha activity between schizophrenic patients and normal people are statistically
      significant. Taken together, the results provide initial evidence that patients
      with schizophrenic disorder may have a common impairment in the protein levels
      and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase
      and a multisubstrate protein phosphatase activator in their lymphocytes.

PMID- 8530530
TI  - Nuclear ultrastructures associated with the RNA synthesis and processing.
AB  - Relatively little is known about the spatial organization of RNA synthesis,
      processing, and transport in (mammalian) cell nuclei. This review summarizes
      results of electron microscopic mapping of RNA synthetic sites and macromolecules
      involved directly, or indirectly, in the metabolism of RNAs in somatic cell
      mammalian nuclei. Significance of these results will be discussed in the context
      of the molecular mechanisms underlying spatial arrangements of RNA metabolism.

PMID- 8530531
TI  - Metabolism of 3H-1 alpha,25-dihydroxyvitamin D3 in cultured human keratinocytes.
AB  - In the present investigation we studied the metabolism of 1 alpha,25-dihydroxy-[1
      beta-3H]vitamin D3 (3H-1,25(OH)2D3) in culture-grown human keratinocytes (CHK).
      Our results showed that the cellular uptake of 3H-1,25(OH)2D3, upon incubation
      with CHK, occurred very rapidly; and it paralleled a decrease in the
      concentration of 3H-1,25(OH)2D3 in the medium. The amount of 3H-calcitroic acid,
      on the other hand, increased slowly in the medium, while the concentration of 3H
      calcitroic acid in the cell remained undetectable during the whole period of
      incubation. When the cells were preincubated with 1,25(OH)2D3 (10(-8)M),
      conversion of 3H-1,25(OH)2D3 to 3H-calcitroic acid increased almost twofold,
      indicating that 1,25(OH)2D3 catalyzed its own catabolism.

PMID- 8530532
TI  - Changes associated with tyrosine phosphorylation during short-term hypoxia in
      retinal microvascular endothelial cells in vitro.
AB  - The occlusion of capillary vessels results in low oxygen tension in adjacent
      tissues which triggers a signaling cascade that culminates in neovascularization.
      Using bovine retinal capillary endothelial cells (BRCEC), we investigated the
      effects of short-term hypoxia on DNA synthesis, phosphotyrosine induction,
      changes in the expression of basic fibroblast growth factor receptor (bFGFR),
      protein kinase C (PKC alpha), heat shock protein 70 (HSP70), and SH2-containing
      protein (SHC). The effect of protein tyrosine kinase (PTK) and phosphatase
      inhibitors on hypoxia-induced phosphotyrosine was also studied. Capillary
      endothelial cells cultured in standard normoxic (pO2 = 20%) conditions were
      quiesced in low serum containing medium and then exposed to low oxygen tension or
      hypoxia (pO2 = 3%) in humidified, 5% CO2, 37 degrees C, tissue culture chambers,
      on a time-course of up to 24 h. DNA synthesis was potentiated by hypoxia in a
      time-dependent manner. This response positively correlated with the cumulative
      induction of phosphotyrosine and the downregulation of bFGFR (M(r) approximately
      85 kDa). Protein tyrosine kinase inhibitors, herbimycin-A, and methyl 2,5
      dihydroxycinnamate, unlike genistein, markedly blocked hypoxia-induced
      phosphotyrosine. Prolonged exposure of cells to phosphatase inhibitor, sodium
      orthovanadate, also blocked hypoxia-induced phosphotyrosine. The expression of
      HSP70, PKC alpha, and SHC were not markedly altered by hypoxia. Taken together,
      these data suggest that short-term hypoxia activates endothelial cell
      proliferation in part via tyrosine phosphorylation of cellular proteins and
      changes in the expression of the FGF receptor. Thus, endothelial cell mitogenesis
      and neovascularization associated with low oxygen tension may be controlled by
      abrogating signaling pathways mediated by protein tyrosine kinase and
      phosphatases.

PMID- 8530533
TI  - Possible role for protein kinase C in the pathogenesis of inborn errors of
      metabolism.
AB  - Protein kinase C (PKC) is a ubiquitous enzyme family implicated in the regulation
      of a large number of short- and long-term intracellular processes. It is
      hypothesized that modulation of PKC activity may represent, at least in part, a
      functional link between mutations (genotype) that lead to the pathological
      accumulation of naturally occurring compounds that affect PKC activity and
      perturbation of PKC-mediated substrate phosphorylation and cellular function in
      the corresponding diseases (phenotype). This model provides a unifying putative
      mechanism by which the phenotypic expression of some inborn errors of metabolism
      may be explained. Recent studies in a cell-free system of human skin fibroblasts
      support the hypothesis that alteration of PKC activity may represent the
      functional link between accumulation of sphingolipids and fatty acyl-CoA esters,
      and perturbation of cell function in sphingolipidoses and fatty acid oxidation
      defects, respectively. Further studies will elucidate the effects of these
      alterations on PKC-mediated short- and long-term cellular functions in these
      diseases, as well as the possible role of PKC in the pathogenesis of other
      diseases.

PMID- 8530534
TI  - Multiphasic modulation of signal transduction into T lymphocytes by
      monoiodoacetic acid as a sulfhydryl reagent.
AB  - Actions of monoiodoacetic acid (MIA) as a sulfhydryl reagent on the different
      stages of the T cell receptor (TCR)-mediated signal transduction were examined.
      MIA (1 mM) prevented anti-TCR (CD3) monoclonal antibody (mAb)-induced energy
      dependent receptor capping but at the same time promoted the anti-CD3 mAb/mitogen
      induced tyrosine phosphorylation of the T cell activation-linked cellular
      proteins of 120, 80, 70, 56, and 40 kDa. Relatively low concentration (0.01 mM)
      of MIA further promoted anti-CD3 mAb-induced transcription of c-fos, production
      of IL-2, and cell surface expression of IL-2 receptors. The MIA-promoted TCR
      mediated IL-2 production actually required signal transduction that could be
      inhibited by cyclosporin A, genistein, or H-7. In contrast, the same
      concentration of MIA as promoted the signal transduction for cell activation
      severely inhibited the anti-CD3 mAb-triggered signal delivery for cell
      proliferation, selectively at its early stage. We conclude from these results
      that MIA differentially affects various steps of signaling into T lymphocytes,
      suggesting that there exist multiple sites of MIA-sensitive or redox-linked
      control in the signal cascade.

PMID- 8530536
TI  - 1,25-dihydroxyvitamin D3: a novel agent for enhancing wound healing.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), has diverse effects in a variety of
      tissues and cell types, including skin. Since 1,25(OH)2D3 affects both fibroblast
      and keratinocytes, we evaluated the effect of 1,25(OH)2D3 on wound healing. We
      investigated the effect of the topically applied 1,25(OH)2D3 or vehicle on the
      healing of cutaneous wounds in rats in a blinded manner. Wound areas were
      measured by planimetry technique. Healing was expressed as the percentage of the
      original wound area that was healed. 1,25(OH)2D3 at concentrations between 5 and
      50 ng/day caused a dose-dependent acceleration of healing. Time course and
      specificity studies indicated that 1,25(OH)2D3 specifically promoted healing
      between 1-5 days after wounding as compared with vitamin D (0.5 microgram/day),
      which showed no significant improvement over control. Our results suggest that
      1,25(OH)2D3 and its analogues may be a new class of compounds that could be
      developed to enhance wound healing.

PMID- 8530535
TI  - Tyrosine protein kinase expression in long-term quiescent WI-38 cells following
      growth factor simulation.
AB  - We have used the WI-38 cell long-term quiescent model system to study the
      regulation of cell cycle progression at the molecular level. By modulating the
      length of time that WI-38 cells are density arrested, it is possible to
      proportionately alter the length of the prereplicative or G-1 phase which the
      cell traverses after growth factor stimulation in preparation for entry into DNA
      synthesis. Stimulation of long- and short-term density arrested WI-38 cells with
      different growth factors or higher concentrations of individual growth factors
      does not alter the time required by long-term cells to enter S after stimulation.
      However, the time during the prereplicative period for which these growth factors
      are needed is different. Long-term quiescent WI-38 cells require EGF to traverse
      the G-0/G-1 border but do not need and apparently cannot respond to IGF-1 during
      the first 10 h after EGF stimulation, the length of the prolongation of the
      prereplicative phase. This suggests that EGF stimulation of long-term quiescent
      WI-38 cells initiates a series of molecular events which make these cells
      "competent" to respond to the "progression" growth factor, IGF-1. In light of the
      well-established role of protein tyrosine kinases in signal transduction, we set
      out to identify, clone, and analyze the expression of receptor and non-receptor
      tyrosine kinases which potentially could play a role during the prolongation of
      the prereplicative phase in making the long-term quiescent WI-38 cells competent
      to respond to IGF-1. We obtained 49 clones representing 11 different receptor and
      non-receptor type protein tyrosine kinases. Analysis of expression of these
      clones revealed a variety of different patterns of expression. However, the most
      striking pattern was exhibited by IGF-1 receptor. Our results suggest that
      induction of IGF-1 receptor mRNA by EGF may be an important event in the
      establishment of competence by EGF in long-term density arrested WI-38 cells.

PMID- 8530537
TI  - Synthesis of stromal glycosaminoglycans in response to injury.
AB  - Our goal is to examine the synthesis and deposition of corneal glycosaminoglycans
      (GAGs) in response to a wound created by the insertion of porous discs into
      stromal interlamellar pockets. The disc and the surrounding stromal tissue were
      assayed and compared to contralateral control stroma and to sham operated corneas
      at 14, 42, and 84 days. The tissue and/or discs were removed and labeled with 35S
      sulfate for 18 h; GAGs were extracted with 4 M guanidine-HCl. Extracts were
      chromatographed on Q-Sepharose columns, bound proteoglycans were eluted with a
      linear salt gradient, and radioactive fractions were analyzed. Total GAG content
      was determined colorimetrically, using dimethylmethylene blue. Specific GAGs were
      determined using enzymatic digestion with selective polysaccharide lyases and
      protein cores were examined using SDS-PAGE. The nonbound fractions from the
      chromatography were assayed for TGF-beta using Western blot analysis and for
      hyaluronic acid using an 125I-radiometric assay. Specific GAGs were localized 42
      days after the disc had been implanted in the stroma. The placement of the discs
      into the stroma resulted in a decrease in the total amount of GAG. However, the
      ratio of dermatan-chondroitin sulfate and heparan sulfate to keratan sulfate
      increased in the surrounding tissue and disc. Hyaluronic acid was elevated at day
      14 in the surrounding tissue, and not until day 84 in the disc. Western blot
      analysis of surrounding tissue extracts revealed forms of TGF-beta that migrated
      with an apparent molecular mass of 63 and 43 kDa. The results indicate that the
      insertion of discs into interlamellar pockets causes changes in the sulfation and
      proportion of the glycosaminoglycans in the surrounding tissue and the disc.
      These changes are coincident with the appearance of TGF-beta. After 84 days, the
      population of glycosaminoglycans in the disc begins to resemble the surrounding
      stroma. This model will allow us to examine further the synthesis and deposition
      of proteins following an extensive wound in which cells must migrate to the wound
      site and then undergo extensive remodeling.

PMID- 8530538
TI  - Steroid-hormone regulation of myosin subunit expression in smooth and cardiac
      muscle.
AB  - We investigated the effects of ovarectomy and the steroid hormones estrogen and
      testosterone on the in vivo expression of heavy (MHC) and light (MLC) chains of
      myosin in the heart, uterus, and aorta of rats. In the heart, ovarectomy
      decreased alpha-MHC expression, while both steroid hormones normalized it.
      Differential steroid hormone effects could be observed on myosin subunit
      expression of smooth muscle. Testosterone but not estrogen normalized the
      ovarectomy-induced decreased expression of SM1 and strongly increased the
      expression of 5'-inserted MHC in the uterus. Estrogen but not testosterone
      normalized the ovarectomy-induced diminished MLC17a expression. In contrast to
      the uterus, no steroid hormone effects on myosin subunit expression could be
      observed in the aorta.

PMID- 8530539
TI  - Purification and stability characterization of a cell regulatory
      sialoglycopeptide inhibitor.
AB  - Previous attempts to physically separate the cell cycle inhibitory and protease
      activities in preparations of a purified cell regulatory sialoglycopeptide
      (CeReS) inhibitor were largely unsuccessful. Gradient elution of the inhibitor
      preparation from a DEAE HPLC column separated the cell growth inhibitor from the
      protease, and the two activities have been shown to be distinct and non
      overlapping. The additional purification increased the specific biological
      activity of the CeReS preparation by approximately two-fold. The major inhibitory
      fraction that eluted from the DEAE column was further analyzed by tricine-SDS
      PAGE and microbore reverse phase HPLC and shown to be homogeneous in nature. Two
      other fractions separated by DEAE HPLC, also devoid of protease activity, were
      shown to be inhibitory to cell proliferation and most likely represented modified
      relatives of the CeReS inhibitor. The highly purified CeReS was chemically
      characterized for amino acid and carbohydrate composition and the role of the
      carbohydrate in cell proliferation inhibition, stability, and protease resistance
      was assessed.

PMID- 8530540
TI  - Further characterization of the human cell multiprotein DNA replication complex.
AB  - Evidence for multiprotein complexes playing a role in DNA replication has been
      growing over the years. We have previously reported on a replication-competent
      multiprotein form of DNA polymerase isolated from human (HeLa) cell extracts. The
      proteins that were found at that time to co-purify with the human cell
      multiprotein form of DNA polymerase included: DNA polymerase alpha, DNA primase,
      topoisomerase I, RNase H, PCNA, and a DNA-dependent ATPase. The multiprotein form
      of the human cell DNA polymerase was further purified by Q-Sepharose
      chromatography followed by glycerol gradient sedimentation and was shown to be
      fully competent to support origin-specific and large T-antigen dependent simian
      virus 40 (SV40) DNA replication in vitro [Malkas et al. (1990b): Biochemistry
      29:6362-6374]. In this report we describe the further characterization of the
      human cell replication-competent multiprotein form of DNA polymerase designated
      MRC. Several additional DNA replication proteins that co-purify with the MRC have
      been identified. These proteins include: DNA polymerase delta, RF-C,
      topoisomerase II, DNA ligase I, DNA helicase, and RP-A. The replication
      requirements, replication initiation kinetics, and the ability of the MRC to
      utilize minichromosome structures for DNA synthesis have been determined. We also
      report on the results of experiments to determine whether nucleotide metabolism
      enzymes co-purify with the human cell MRC. We recently proposed a model to
      represent the MRC that was isolated from murine cells [Wu et al. (1994): J Cell
      Biochem 54:32-46]. We can now extend this model to include the human cell MRC
      based on the fractionation, chromatographic and sedimentation behavior of the
      human cell DNA replication proteins. A full description of the model is
      discussed. Our experimental results provide further evidence to suggest that DNA
      synthesis is mediated by a multiprotein complex in mammalian cells.

PMID- 8530541
TI  - Ischemia-induced neuronal damage: a role for calcium/calmodulin-dependent protein
      kinase II.
AB  - Calcium/calmodulin-dependent protein kinase II (CaM-kinase) is a central enzyme
      in regulating neuronal processes. Imbalances in the activity and distribution of
      this enzyme have been reported following in vivo ischemia, and sustained
      decreases in activity correlate with subsequent neuronal death. In this report,
      mice that had been rendered deficient in the alpha subunit of CaM-kinase using
      gene knock-out technology were utilized to determine whether this enzyme is
      causally related to ischemic damage. Using a focal model of cerebral ischemia, we
      showed that homozygous knock-out mice lacking the alpha subunit exhibited an
      infarct volume almost twice that of wild-type litter mates. Heterozygous mice
      exhibited slightly less damage following ischemia than did homozygous mice, but
      infarct volumes remained significantly larger than those of wild-type litter
      mates. We conclude that reduced amounts of the alpha subunit of CaM-kinase
      predisposes neurons to increased damage following ischemia and that any
      perturbation that decreases the amount or activity of the enzyme will produce
      enhanced susceptibility to neuronal damage.

PMID- 8530542
TI  - Brain temperature alters hydroxyl radical production during cerebral
      ischemia/reperfusion in rats.
AB  - Selective neuronal cell death in the CA1 pyramidal cells of the hippocampus and
      neurons of the dorsolateral striatum as a consequence of brain
      ischemia/reperfusion (IR) can be ameliorated with brain hypothermia. Since
      postischemic injury is mediated partially by chemical production of reactive
      oxygen species (ROS), decreased ROS production may be one of the mechanisms
      responsible for cerebral protection by hypothermia. To determine if ischemic
      brain temperature alters ROS production, reversible IR was produced in rats by
      occlusion of both carotid arteries with hemorrhagic hypotension. After 15 min of
      ischemia, circulation was restored for 60 min. Brain temperature was maintained
      during ischemia at either 30, 36, or 39 degrees C and kept at 36-37 degrees C
      after reperfusion. Using cerebral microdialysis, we measured nonenzymatic
      hydroxylation of salicylate by HPLC with electrochemical detection in the
      hippocampus. CBF was also compared among the groups during IR. The results were
      that normothermic animals during reperfusion had persistently increased levels of
      the salicylate hydroxylation product, 2,3-dihydroxybenzoic acid (2,3-DHBA),
      reaching 251% of control at 60 min. This increase in 2,3-DHBA production was
      potentiated after 60 min of reperfusion (406% of control) with ischemic
      hyperthermia. In hypothermic ischemia, 2,3-DHBA production at 60 min was
      attenuated to 160% of control. CBF decreased to approximately 5% of baseline
      value during ischemia, but increased three- to four-fold relative to control in
      all three groups. Therefore, the effects of ischemic brain temperature on 2,3
      DHBA production did not correlate with changes in CBF during IR. We conclude that
      brain-temperature-related changes in OH.production are readily detected in the
      rat and decreased ROS generation may contribute to cerebral protection afforded
      by hypothermia during brain ischemia.

PMID- 8530543
TI  - Short therapeutic window for MK-801 in transient focal cerebral ischemia in
      normotensive rats.
AB  - The present study investigates the role of N-methyl-D-aspartate (NMDA) receptors
      in a model of transient focal cerebral ischemia in normotensive rats. The left
      middle cerebral artery and both common carotid arteries were occluded for 60 min.
      Preliminary studies indicated that this gave reproducible infarctions of the
      cortex and striatum. These infarctions were the result of severe ischemia
      followed by complete reperfusion after clamp removal, as showed by striatal
      tissue Po2 monitoring. Microdialysis indicated that glutamate concentration
      increased immediately after occlusion and returned to the baseline value 40 min
      after clamp removal. MK-801 (1 mg kg-1 i.v.), an antagonist of the NMDA
      glutamatergic receptor, reduced the cortical infarct volume by 29% (p < 0.001)
      and the striatal infarct volume by 14% (p < 0.05) when given just prior to
      ischemia, but had no neuroprotective activity when given 30 min after the onset
      of ischemia. This short therapeutic window for MK-801 suggests that NMDA
      receptors play only a transient role in reversible focal ischemia in rats.

PMID- 8530544
TI  - Secondary elevation of extracellular neurotransmitter amino acids in the
      reperfusion phase following focal cerebral ischemia.
AB  - The purpose of this study was to evaluate amino acid neurotransmitter dynamics in
      the reperfusion phase after transient cerebral ischemia. In vivo microdialysis
      was used to measure extracellular amino acid levels in a rabbit model of focal
      ischemia. During 30 min of transient ischemia (n = 5), small but significant (p <
      0.05) increases in glutamate, aspartate, gamma-aminobutyric acid (GABA), and
      taurine were noted. These elevations rapidly returned to baseline levels upon
      recirculation and remained constant for up to 5.5 h of reperfusion. In rabbits
      subjected to 2 h of transient ischemia (n = 5), two phases of amino acid release
      were seen. During ischemia, large (5- to 50-fold) elevations in glutamate,
      aspartate, GABA, and taurine occurred, as expected. These elevations rapidly
      normalized upon unocclusion. However, significant (p < 0.05) secondary elevations
      in glutamate, aspartate, and GABA occurred after 2-4 h of reperfusion. Regression
      analysis demonstrated significant correlations between primary (ischemic) and
      secondary (reperfusion) efflux. In permanent ischemia (n = 5), amino acid levels
      remained elevated throughout the entire experiment. Secondary elevations in
      excitatory amino acids may further contribute to the excitotoxic cascade during
      reperfusion.

PMID- 8530545
TI  - Bioenergetic recovery following ischemia in brain slices studied by 31P-NMR
      spectroscopy: differential age effect of depolarization mediated by endogenous
      nitric oxide.
AB  - Proximate neurotoxic mechanisms during postischemic recovery may be influenced by
      stage of development and complicating factors such as cortical spreading
      depression or secondary brain insult. Using 31P nuclear magnetic resonance
      spectroscopy, we have monitored pH and cellular energy metabolites
      phosphocreatine (PCr) and ATP in the ex vivo rat cerebral cortex before, during,
      and after substrate and oxygen deprivation, which represents "in vitro ischemia."
      There were important developmental differences in resistance and response to an
      ischemic insult. Twenty-one-day-old (P21) rat cortical slices had no detectable
      beta-ATP or PCr at the end of a 20-min insult, while 7-day-old (P7) slices had 50
      +/- 13.7% (mean +/- SD, n = 12) and 17 +/- 14.8% relative to preischemia levels,
      respectively. Postischemic depolarization resulted in age-dependent effects on
      PCr (p < 0.05): In the older tissue, depolarization significantly worsened the
      recovery of PCr, whereas in young tissue it ameliorated recovery. This
      amelioration could be prevented by inhibiting nitric oxide production with
      methylene blue (depolarization-methylene blue interaction, p < 0.05) and enhanced
      by administration of the nitric oxide donor glyceryl trinitrate (GTN; p < 0.01).
      However, in P21 tissue, GTN further exacerbated injury (age-GTN interaction, p <
      0.01). Therefore, in this vascular-independent preparation, a neuronal or glial
      nitric oxide-dependent mechanism appears to confer improved postischemic
      bioenergetic recovery in the developing brain compared with the mature brain.

PMID- 8530546
TI  - Cerebral metabolism following neonatal or adult hemineodecortication in cats: I.
      Effects on glucose metabolism using [14C]2-deoxy-D-glucose autoradiography.
AB  - In the cat, cerebral hemispherectomy sustained neonatally results in a remarkable
      degree of recovery and/or sparing of function as compared with the effects of a
      similar lesion but sustained in adulthood. We have proposed that this effect is
      due to a combination of reduced neuronal loss within partially denervated
      structures and a lesion-induced reorganization of corticofugal projections
      arising from the remaining intact hemisphere in the neonatally lesioned animal.
      The current study was designed to assess the physiological consequences of these
      anatomical changes utilizing [14C]2-deoxy-D-glucose autoradiography. A total of
      17 adult cats were studied. Seven animals served as intact controls, five
      received a left cerebral hemineodecortication as neonates (NH; mean age 11.4
      days), and five sustained the same lesion in adulthood (AH). Histological
      analysis indicated that the lesion was very similar between the two age groups
      and essentially represented a unilateral hemineodecortication. Local CMRglc
      (LCMRglc; mumol 100 g-1 min-1) values were calculated for 50 structures
      bilaterally and indicated that in the remaining intact contralateral (right)
      cerebral cortex (including all areas measured), AH cats exhibited a significantly
      (p < 0.05) lower level of LCMRglc (ranging from 20 to 72 mumol 100 g-1 min-1)
      than NH (ranging from 49 to 81 mumol 100 g-1 min-1). In comparison, the rates of
      NH cats within the cerebral cortex were very similar to those seen in intact
      animals (ranging from 48 to 119 mumol 100 g-1 min-1). Ipsilateral to the lesion
      in AH cats, the structures spared by the resection, including the basal ganglia
      and thalamus, exhibited LCMRglc rates of between 23 and 69 mumol 100 g-1 min-1,
      which were significantly lower (p < 0.05) than in NH cats (range 47-72 mumol 100
      g-1 min-1). Considering all structures, both age-at-lesion groups exhibited a
      lower level of metabolism compared with similar measurements for intact control
      animals (LCMRglc range 45-75 mumol 100 g-1 min-1). However, this depression of
      glucose metabolism was more pronounced in the AH cats (p < 0.05). These results
      indicate that following neonatal hemineodecortication, LCMRglc is maintained at a
      higher level in many regions of the brain than in animals that sustain the same
      resection in adulthood. This higher level of glucose metabolism in NH animals
      suggests that the lesion-induced anatomical reorganization of structures not
      directly injured by the lesion plays a functional role that is probably
      responsible for the greater degree of recovery and/or sparing of function in
      these early lesioned cats.

PMID- 8530547
TI  - Absence seizures induce a decrease in cerebral blood flow: human and animal data.
AB  - Our previous studies on cerebral metabolic activity in genetic absence epilepsy
      rats from Strasbourg (GAERS) were in favor of decreased functional activity
      during absences and normal or increased interictal activity. To ascertain that
      hypothesis, in the present study we performed continuous measurements of CBF in
      both children with typical absence epilepsy and GAERS, using Doppler
      ultrasonography and laser-Doppler flowmetry, respectively. CBF fluctuations
      during absences were recorded in four children between 5 and 6 years of age and
      16 adult GAERS. In both children and animals, CBF measured in the middle cerebral
      artery and cortical capillaries, respectively, significantly decreased by a
      median value of 20-24% under basal levels during spontaneous absences. In GAERS,
      CBF levels were continuously decreased during haloperidol-induced absence status
      epilepticus, while they were not affected by ethosuximide. Conversely, convulsive
      seizures induced in rats either by kainate or picrotoxin led to a 175-664%
      increase in CBF levels. In conclusion, the present data show that during
      spontaneous absences, CBF decreases under basal levels in both cortical
      capillaries (GAERS) and the middle cerebral artery (children). Moreover, these
      fluctuations occur in vessels with normal vascular reactivity, are not mediated
      by changes in PO2, PCO2, or arterial blood pressure, and represent rather a
      response to reduced metabolic demand.

PMID- 8530548
TI  - Laser-Doppler evaluation of rat brain microcirculation: comparison with the [14C]
      iodoantipyrine method suggests discordance during cerebral blood flow increases.
AB  - Laser-Doppler flowmetry (LDF) is very popular for measurements of dynamic changes
      of cerebral blood flow (CBF). We studied whether changes of CBF measured by LDF
      correlate with CBF measured by the [14C]iodoantipyrine (IAP) technique in the
      range relevant for most physiological experiments (-30-(+)130%). LDF was recorded
      biparietally by two laser-Doppler probes in halothane-anesthetized rats. Absolute
      CBF was measured in tissue samples of both parietal cortices after
      [14C]iodoantipyrine was given i.v. CBF of one hemisphere was reduced by an
      episode of cortical spreading depression (CSD), which markedly reduces the
      responsiveness of the ipsilateral cortical CBF to vasoactive stimuli for up to 30
      min, while CBF regulation of the contralateral cortex remains intact. CBF was
      measured under normoventilated, hypercapnic, and hypoxic conditions. The relative
      changes of CBF measured by the LDF technique were independent of the preceding
      baseline LDF value. Absolute CBFIAP values correlated poorly to the
      simultaneously recorded arbitrary LDF values (r = 0.44). In contrast, the ratio
      of CBFIAP values correlated with the ratio of the relative LDF changes between
      the two hemispheres (p < 0.001). At reduced CBF, no significant difference was
      found between methods. At increased CBF, however, LDF was greater than CBFIAP, as
      indicated by a slope of correlation of 1.45 (p < 0.005).

PMID- 8530549
TI  - Hemodynamic simulation study of cerebral arteriovenous malformations. Part 2.
      Effects of impaired autoregulation and induced hypotension.
AB  - The hemodynamic changes occurring during obliteration procedures for
      arteriovenous malformations (AVM) have not been fully elucidated. Therefore, we
      undertook a simulation study using a compartmental flow model to investigate the
      role of altered autoregulatory conditions in the development of hyperperfusion
      during obliteration of large high-flow AVM. Induced hypotension was also
      simulated to evaluate its usefulness in reducing the incidence and severity of
      the event. As the AVM flow was decreased during the obliteration procedures,
      feeder pressure increased and drainer pressure decreased, with a concomitant
      increase in the perfusion pressure in the brain tissue surrounding the AVM.
      Cerebral blood flow (CBF) remained constant at 50 ml 100 g-1 min-1 in the
      presence of autoregulation and increased to 67 ml 100 g-1 min-1 in its absence.
      When the lower limit of the autoregulatory pressure range (LAR) was shifted from
      60 to 50 or 40 mm Hg, the flow volume increased markedly from 67 to 77 ml 100 g-1
      min-1 or to 92 ml 100 g-1 min-1 after complete obliteration. Decrease in LAR
      would be a cause of the hyperperfusion. Induced systemic hypotension was found to
      be effective in reducing the magnitude of these hemodynamic changes, when
      induction was appropriately performed in a stepwise fashion. A simulation study
      is useful in clarifying the various hemodynamic changes that develop during the
      treatment of AVM.

PMID- 8530550
TI  - Acute focal ischemia-induced alterations in MAP2 immunostaining: description of
      temporal changes and utilization as a marker for volumetric assessment of acute
      brain injury.
AB  - The utility of microtubule-associated protein 2 (MAP2) immunostaining as a marker
      of acute focal ischemic injury was investigated. Permanent middle cerebral artery
      occlusion (MCAO) elicited a rapid reduction in MAP2 immunostaining that was
      visible 1 h post-MCAO and that increased in intensity and area encompassed over
      time. The ischemic lesion borders were well defined by loss of MAP2
      immunostaining, but alterations in staining within the lesion were more
      heterogeneous. Lesion volume increased significantly from 1 to 4 h post-MCAO
      (from 63.8 +/- 10.8 to 111.3 +/- 19.0 mm3, mean +/- SD). Thus, MAP2
      immunostaining is a sensitive, quantifiable indicator of acute brain injury
      following focal ischemia.

PMID- 8530551
TI  - Oxygen radicals do not play a role in arteriolar dilation during cortical
      spreading depression.
AB  - This study examined the role of oxygen radicals in pial arteriolar changes during
      cortical spreading depression (CSD). CSD was induced by microinjection of 5% KCl
      in anesthetized adult rabbits. Pial diameter was measured with a closed cranial
      window and intravital microscopy. During control CSD (n = 12), the dilation
      amplitude and area were 55 +/- 14% and 693 +/- 69 mm2 (baseline = 76 +/- 14
      microns), respectively. Oxygen radical scavengers, superoxide dismutase (SOD; 105
      U/ml, topical application; n = 5) or oxypurinol (50 mg/kg i.v.; n = 7), did not
      alter the dilation amplitude and area or change onset latency during CSD.
      Further, SOD and oxypurinol did not prevent NG-nitro-L-arginine from attenuating
      arteriolar dilation during CSD (n = 12). We conclude that oxygen radicals do not
      play a role in the transient dilation of cerebral arterioles during CSD.

PMID- 8530552
TI  - Frequency-dependent changes of regional cerebral blood flow during finger
      movements.
AB  - To study the effect of the repetition rate of a simple movement on the
      distribution and magnitude of neuronal recruitment, we measured regional CBF
      (rCBF) in eight normal volunteers, using positron emission tomography and 15O
      labeled water. An auditory-cued, repetitive flexion movement of the right index
      finger against the thumb was performed at very slow (0.25 and 0.5 Hz), slow (0.75
      and 1 Hz), fast (2 and 2.5 Hz), and very fast (3 and 4 Hz) rates. The increase of
      rCBF during movement relative to the resting condition was calculated for each
      pair of movement conditions. Left primary sensorimotor cortex showed no
      significant activation at the very slow rates. There was a rapid rise of rCBF
      between the slow and the fast rates, but no further increase at the very fast
      rates. The right cerebellum showed similar changes. Changes in the left primary
      sensorimotor cortex and the cerebellum likely reflect the effect of the movement
      rate. The posterior supplementary motor area (SMA) showed its highest activation
      at the very slow rates but no significant activation at the very fast rates.
      Changes correlating with those in the SMA were found in the anterior cingulate
      gyrus, right prefrontal area, and right thalamus. The decreases in CBF may
      reflect a progressive change in performance from reactive to predictive.

PMID- 8530553
TI  - Cholinergic projection from the basal forebrain and cerebral glucose metabolism
      in rats: a dynamic PET study.
AB  - To investigate the influence of cholinergic projections from the basal forebrain
      on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of
      glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat
      basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic
      acid (BPA), and compared the results with those obtained after lesioning the
      basal forebrain with ibotenic acid, as well as with those from a sham-operated
      control group. CMRGlu was measured using positron emission tomography (PET) with
      [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3
      (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA
      injected side and in the ibotenic acid-treated group, whereas K1 (transport rate
      of FDG from the plasma to brain) showed no marked changes. At 3 weeks
      postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered
      to levels similar to those of the sham-operated group. The main difference
      between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on
      the side contralateral to the operation in the former, while such reduction was
      confined to the ipsilateral hemisphere in the latter. The present results
      indicate that the cholinergic system in the basal forebrain regulates cerebral
      cortex glucose metabolism through direct excitation of cortical neurons.

PMID- 8530555
TI  - Clinical outcome in ischemic stroke predicted by early diffusion-weighted and
      perfusion magnetic resonance imaging: a preliminary analysis.
AB  - Perfusion and diffusion-weighted magnetic resonance imaging (MRI) can
      demonstrate, respectively, cerebral ischemia and ischemic brain injury in the
      first several hours after onset of symptoms, when proton density and T2-weighted
      MRI may appear normal. It is hypothesized that these techniques could distinguish
      regions destined for infarction from those that will not progress to infarction.
      We provide preliminary evidence from an analysis of 19 patients with severely
      disabling clinical deficits attributable to ischemia in at least an entire
      division of the middle cerebral artery, that initial perfusion and diffusion MRI
      were more accurate than conventional MRI in predicting no, partial or complete
      improvement--17 of 19 cases (p < 0.0001) versus 10 of 19 cases, respectively. In
      the subset of patients studied within 6 h of onset, diffusion/perfusion MRI was
      an even better predictor than conventional MRI--11 of 12 versus four of 12,
      respectively. In this small sample of patients with severe clinical deficits,
      perfusion and diffusion MRI were highly accurate in distinguishing those who
      would improve from those who would not. These results need to be confirmed in a
      larger prospective study, which may support a future role in the initial
      screening, selection, and evaluation of patients with stroke for acute
      pharmacologic interventions.

PMID- 8530556
TI  - Temporal correlation analysis of penumbral dynamics in focal cerebral ischemia.
AB  - A novel temporal correlation technique was used to map the first-pass transit of
      iodinated contrast agents through the brain. Transit profiles after bolus
      injections were measured with dynamic computed tomography (CT) scanning (1
      image/s over 50 s). A rabbit model of focal cerebral ischemia (n = 6) was used,
      and dynamic CT scans were performed at 30, 60, 90, and 120 min postocclusion.
      Within the ischemic core, no bolus transit was detectable, demonstrating that
      complete ischemia was present after arterial occlusion. In the periphery of the
      ischemic distribution, transit dynamics showed smaller peaks, broadened profiles,
      and overall delay in bolus transit. A cross-correlation method was used to
      generate maps of delays in ischemic transit profiles compared with normal transit
      profiles from the contralateral hemisphere. These maps showed that penumbral
      regions surrounding the ischemic core had significantly delayed bolus transit
      profiles. Enlargement of the ischemic core over time (from 30 to 120 min
      postocclusion) was primarily accomplished by the progressive deterioration of the
      penumbral regions. These results suggest that (a) temporal correlation methods
      can define regions of abnormal perfusion in focal cerebral ischemia, (b)
      peripheral regions of focal cerebral ischemia are characterized by delays in
      bolus transit profiles, and (c) these regions of bolus transit delay deteriorate
      over time and thus represent a hemodynamic penumbra.

PMID- 8530554
TI  - Comparison of methods for analysis of clinical [11C]raclopride studies.
AB  - Five different methods for the estimation of the binding potential, a measure of
      Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a
      dose ranging study of the neuroleptic CP-88,059-01. Binding potential was
      estimated indirectly, from distribution volumes in striatum and cerebellum, using
      both single- and two-tissue compartment models with a metabolite-corrected plasma
      curve as input function. The two-tissue compartment model was also used for a
      direct estimate of the binding potential. In addition, a direct estimate was
      obtained from the reference tissue compartment model using the cerebellum as
      indirect input function. Finally, an estimate of binding potential was calculated
      from the ratio of striatum over cerebellum counts at late times after injection.
      The estimates of striatum binding potential from all methods, except the direct
      determination using a two-tissue compartment model with metabolite-corrected
      plasma input function, correlated with each other. Use of an average metabolite
      correction resulted in only a small reduction in accuracy in this series of
      normal subjects. The reference tissue model provided estimates of the binding
      potential with the same sensitivity for detecting changes as those methods that
      required a metabolite-corrected plasma input function. This indicates that for
      routine analysis of clinical [11C]raclopride studies, no arterial cannulation is
      required. The range of normal values was significantly less variable with the
      reference tissue method than when simple striatum-to-cerebellum ratios were used.

PMID- 8530557
TI  - Forebrain ischemia increases GLUT1 protein in brain microvessels and parenchyma.
AB  - Glucose transport into nonneuronal brain cells uses differently glycosylated
      forms of the glucose transport protein, GLUT1. Microvascular GLUT1 is readily
      seen on immunocytochemistry, although its parenchymal localization has been
      difficult. Following ischemia, GLUT1 mRNA increases, but whether GLUT1 protein
      also changes is uncertain. Therefore, we examined the immunocytochemical
      distribution of GLUT1 in normal rat brain and after transient global forebrain
      ischemia. A novel immunocytochemical finding was peptide-inhibitable GLUT1
      immunoreactive staining in parenchyma as well as in cerebral microvessels. In
      nonischemic rats, parenchymal GLUT1 staining co-localizes with glial fibrillary
      acidic protein (GFAP) in perivascular foot processes of astrocytes. By 24 h after
      ischemia, both microvascular and nonmicrovascular GLUT1 immunoreactivity
      increased widely, persisting at 4 days postischemia. Vascularity within sections
      of brain similarly increased after ischemia. Increased parenchymal GLUT1
      expression was paralleled by staining for GFAP, suggesting that nonvascular GLUT1
      overexpression may occur in reactive astrocytes. A final observation was a rapid
      expression of inducible heat shock protein (HSP)70 in hippocampus and cortex by
      24 h after ischemia. We conclude that GLUT1 is normally immunocytochemically
      detectable in cerebral microvessels and parenchyma and that parenchymal
      expression occurs in some astroglia. After global cerebral ischemia, GLUT1
      overexpression occurs rapidly and widely in microvessels and parenchyma; its
      overexpression may be related to an immediate early-gene form of response to
      cellular stress.

PMID- 8530558
TI  - Nonparametric analysis of statistic images from functional mapping experiments.
AB  - The analysis of functional mapping experiments in positron emission tomography
      involves the formation of images displaying the values of a suitable statistic,
      summarising the evidence in the data for a particular effect at each voxel. These
      statistic images must then be scrutinised to locate regions showing statistically
      significant effects. The methods most commonly used are parametric, assuming a
      particular form of probability distribution for the voxel values in the statistic
      image. Scientific hypotheses, formulated in terms of parameters describing these
      distributions, are then tested on the basis of the assumptions. Images of
      statistics are usually considered as lattice representations of continuous random
      fields. These are more amenable to statistical analysis. There are various
      shortcomings associated with these methods of analysis. The many assumptions and
      approximations involved may not be true. The low numbers of subjects and scans,
      in typical experiments, lead to noisy statistic images with low degrees of
      freedom, which are not well approximated by continuous random fields. Thus, the
      methods are only approximately valid at best and are most suspect in single
      subject studies. In contrast to the existing methods, we present a nonparametric
      approach to significance testing for statistic images from activation studies.
      Formal assumptions are replaced by a computationally expensive approach. In a
      simple rest-activation study, if there is really no activation effect, the
      labelling of the scans as "active" or "rest" is artificial, and a statistic image
      formed with some other labelling is as likely as the observed one. Thus,
      considering all possible relabellings, a p value can be computed for any suitable
      statistic describing the statistic image. Consideration of the maximal statistic
      leads to a simple nonparametric single-threshold test. This randomisation test
      relies only on minimal assumptions about the design of the experiment, is
      (almost) exact, with Type I error (almost) exactly that specified, and hence is
      always valid. The absence of distributional assumptions permits the consideration
      of a wide range of test statistics, for instance, "pseudo" t statistic images
      formed with smoothed variance images. The approach presented extends easily to
      other paradigms, permitting nonparametric analysis of most functional mapping
      experiments. When the assumptions of the parametric methods are true, these new
      nonparametric methods, at worst, provide for their validation. When the
      assumptions of the parametric methods are dubious, the nonparametric methods
      provide the only analysis that can be guaranteed valid and exact.

PMID- 8530559
TI  - Effects of hypoxia-ischemia on GLUT1 and GLUT3 glucose transporters in immature
      rat brain.
AB  - Cerebral hypoxia-ischemia produces major alterations in energy metabolism and
      glucose utilization in brain. The facilitative glucose transporter proteins
      mediate the transport of glucose across the blood-brain barrier (BBB) (55 kDa
      GLUT1) and into the neurons and glia (GLUT3 and 45 kDa GLUT1). Glucose uptake and
      utilization are low in the immature rat brain, as are the levels of the glucose
      transporter proteins. This study investigated the effect of cerebral hypoxia
      ischemia in a model of unilateral brain damage on the expression of GLUT1 and
      GLUT3 in the ipsilateral (damaged, hypoxic-ischemic) and contralateral
      (undamaged, hypoxic) hemispheres of perinatal rat brain. Early in the recovery
      period, both hemispheres exhibited increased expression of BBB GLUT1 and GLUT3,
      consistent with increased glucose transport and utilization. Further into
      recovery, BBB GLUT1 increased and neuronal GLUT3 decreased in the damaged
      hemisphere only, commensurate with neuronal loss.

PMID- 8530560
TI  - Heat-shock protein and C-fos expression in focal microvascular brain damage.
AB  - Cortical brain damage was produced in rats by a focal pulse from a Nd-YAG laser,
      and evolution of the lesion was evaluated at 30 min, and 2, 8, and 24 h with
      respect to microvascular perfusion, blood-brain barrier (BBB) permeability, and
      expression of both the heat-shock/stress protein, hsp72, and the c-fos proto
      oncogene transcription factor. A double-labeling fluorescence technique employing
      intravenously injected Evans blue albumin (EBA) and fluorescein-labeled dextran
      was used to map and measure BBB damage and microvascular perfusion in fresh
      frozen brain sections. Hsp72 and c-fos mRNAs were localized by in situ
      hybridization, and the respective proteins were identified by
      immunocytochemistry. Parallel sections were stained for glial fibrillary acidic
      protein and for routine histologic examination. Striking hsp72 mRNA expression
      was evident by 2 h in an approximately 300 microns wide rim surrounding an area
      of expanding BBB damage. Increased hsp72 mRNA was observed only in regions of
      preserved microcirculation, where the hsp72 protein was subsequently localized
      exclusively in the vasculature at 24 h after the insult. Hsp72-positive
      endothelial cells spanned the narrow margin between the lesion and histologically
      normal, glial fibrillary acidic protein (GFAP)-positive cortical tissue. There
      was no hsp72 expression in the area of subcortically migrating edema fluid.
      Inductions of c-fos mRNA and Fos protein were not strikingly evident around the
      focal brain lesion, but were observed transiently throughout the injured
      hemisphere at 30 min and 2.5 h, respectively, indicating that spreading
      depression was triggered by the focal injury. These results are in striking
      contrast to those previously obtained from studies of models of focal ischemic or
      traumatic brain injury, which are characterized by a complex pattern of glial and
      neuronal hsp72 expression in the periphery of an infarct, and which suggest that
      the tightly demarcated lesion produced by the Nd-YAG laser lacks these components
      of graded injury that are evident following other types of focal brain damage.

PMID- 8530561
TI  - Simultaneous measurement of salicylate hydroxylation and glutamate release in the
      penumbral cortex following transient middle cerebral artery occlusion in rats.
AB  - Using the microdialysis technique and laser-Doppler flowmetry, we performed
      simultaneous measurement of salicylate hydroxylation and glutamate release along
      with local CBF in the ischemic penumbral cortex of rat brain subjected to
      normothermic transient middle cerebral artery (MCA) occlusion. Cortical CBF fell
      to 24 +/- 11% (mean +/- SD) during ischemia and recovered to 84 +/- 16% during
      reperfusion. Extracellular glutamate levels increased by 6.5-fold above baseline
      10 min following MCA occlusion but subsequently returned to near baseline levels
      in spite of the persistent ischemia. Increase in 2,3- and 2,5-dihydroxybenzoic
      acid (DHBA) concentrations in the microdialysis perfusate was confirmed during
      both ischemia and reperfusion phase. Although the temporal profile and amount of
      salicylate hydroxylation were heterogeneous among individual animals, integrated
      2,3-DHBA concentrations during reperfusion were correlated positively with
      integrated glutamate concentrations during ischemia and negatively with mean
      postischemic CBF. These relationships suggest a possible association of the
      enhanced production of 2,3-DHBA during reperfusion with larger amounts of
      intraischemic glutamate release and lower levels of post-ischemic CBF.

PMID- 8530563
TI  - Detection of HIV-1 infection in vitro using NASBA: an isothermal RNA
      amplification technique.
AB  - Establishment of a sensitive infection assay for HIV-1 is essential for
      successful screening of antiviral agents and neutralizing antibodies. In this
      report, an infection assay is described which measures the expression of viral
      genomic RNA and spliced mRNA intermediates in infected cells by an amplification
      based technique called NASBA. The extreme sensitivity of this method permits the
      detection of viral RNA in peripheral blood mononuclear cells (PBMC) within 48 h
      of infection by a low dose of virus. Similarly, spliced HIV-1 mRNA could be
      detected within 24 h of infection of CEM cells by HIV-1IIIB. This NASBA-based
      infection assay was shown to titer the neutralization of the HIV-1IIIB isolate by
      serum from an infected human and by a monoclonal antibody to gp120. Furthermore,
      the inhibitory effects of azidothymidine (AZT) and soluble CD4 on HIV-1IIIB
      infection were quantitated by this assay. The early detection of virus by NASBA
      minimizes the contribution of secondary infection, thereby permitting more
      accurate evaluation of antiviral agents and neutralizing antibodies. This assay
      may be useful for the study of infection of phenotypically distinct HIV-1
      isolates, which differ in terms of their replication kinetics.

PMID- 8530562
TI  - Treatment of vacutainers for use in the analysis of volatile organic compounds in
      human blood at the low parts-per-trillion level.
AB  - Vacutainers that are routinely used for blood collection contain significant
      amounts of volatile organic compounds (VOCs). These VOCs interfere with the low
      parts-per-trillion analysis of VOCs in whole blood either by causing false
      positives or by masking the presence of VOCs because of high background levels.
      Benzene, bromoform, ethylbenzene, m/p-xylene, o-xylene, styrene, and various
      hydrocarbons are the most significant sources of VOC contamination present in the
      vacutainers. A method of removing VOCs from 10-mL gray-top vacutainers is
      presented. This method uses a combination of heat and vacuum to reduce the VOCs
      to levels compatible with low parts-per-trillion analysis of VOCs in whole blood.

PMID- 8530564
TI  - Simple concentration method for bacteriophages of Bacteroides fragilis in
      drinking water.
AB  - A membrane of inorganic material with a honeycomb pore structure was used to
      concentrate phages infecting Bacteroides fragilis from drinking water. Phages
      were removed from the membrane with 0.25 M glycine buffer pH 9.5. Phages were not
      inactivated by storage in this buffer neutralized to pH 7.0 for at least 9 days
      at 4 degrees C. The method allows recovery of around 50% in drinking water. When
      the turbidity of the water increased, the efficiency of the concentration
      decreased markedly. The efficiency of concentration was evaluated versus a
      presence/absence test in 317 water samples with turbidity level below the
      threshold of drinking water. Results obtained by concentration of 11 provided
      data which were significantly more informative than the presence/absence tests
      carried out on 100 ml. A number of additional tests carried out with both somatic
      and F-specific coliphages indicated that these conclusions can be extended to
      these groups of bacteriophages.

PMID- 8530565
TI  - Centrifugal enhancement of retroviral mediated gene transfer.
AB  - Centrifugation has been used for many years to enhance infection of cultured
      cells with a variety of different types of viruses, but it has only recently been
      demonstrated to be effective for retroviruses (Ho et al. (1993) J. Leukocyte
      Biol. 53, 208-212; Kotani et al. (1994) Hum. Gene Ther. 5, 19-28). Centrifugation
      was investigated as a means of increasing the transduction of a retroviral vector
      for gene transfer into cells with the potential for transplantation and
      engraftment in human patients suffering from genetic disease, i.e., gene therapy.
      It was found that centrifugation significantly increased the rate of transduction
      into adherent murine fibroblasts and into non-adherent human hematopoietic cells,
      including primary CD34+ enriched cells. The latter samples include cells capable
      of reconstitution of hematopoiesis in myeloablated patients. As a step toward
      optimization of this method, it was shown that effective transduction is: (1)
      achieved at room temperature; (2) directly related to time of centrifugation and
      to relative centrifugal force up to 10,000 g; (3) independent of volume of
      supernatant for volumes > or = 0.5 ml using non-adherent cell targets in test
      tubes, but dependent upon volume for coverage of adherent cell targets in flat
      bottom plates; and (4) inversely related to cell numbers per tube using non
      adherent cells. The results support the proposal that centrifugation increases
      the reversible binding of virus to the cells, and together with results reported
      by Hodgkin et al. (Hodgkin et al. (1988) J. Virol. Methods 22, 215-230), these
      data support a model in which the centrifugal field counteracts forces of
      diffusion which lead to dissociation during the reversible phase of binding.

PMID- 8530567
TI  - Comparative study of conventional and novel strategies for the detection of
      hepatitis C virus RNA in serum: amplicor, branched-DNA, NASBA and in-house PCR.
AB  - The aim of this study was to compare the sensitivity and specificity of
      conventional procedures (in-house one-stage polymerase chain reaction (PCR) and
      in-house nested PCR) and of new technologies (rTth DNA polymerase (Amplicor),
      branched-DNA, NASBA (nucleic acid amplification system)) for the qualitative
      detection of hepatitis C virus (HCV) RNA in serum of HCV-infected individuals.
      Serum samples from 37 anti-HCV-positive individuals (15 with a normal alanine
      aminotransferase (ALT) level, 22 with an elevated ALT level) and 10 anti-HCV
      negative individuals as negative controls were studied. A second panel, including
      9 diluted serum samples (from 1/10 to 1/100,000) was constituted to establish the
      differences of sensitivity of the 5 procedures with small quantities of HCV RNA
      in the serum. The anti-HCV-positive individuals with elevated ALT gave positive
      results with all 5 procedures. In patients with a normal ALT level, the assays
      with the highest sensitivity were Amplicor, NASBA and nested RT-PCR, followed by
      one-stage RT-PCR, then branched-DNA. One false-positive result was observed with
      Amplicor, and two with in-house nested PCR. On diluted samples, Amplicor, NASBA
      and nested PCR appeared more sensitive than one-stage PCR and branched-DNA. It is
      concluded that new procedures have satisfactory sensitivity and specificity and
      could advantageously replace the conventional PCR procedures for the routine
      qualitative detection of serum HCV RNA.

PMID- 8530566
TI  - Construction and insect larval expression of recombinant vesicular stomatitis
      nucleocapsid protein and its use in competitive ELISA.
AB  - The gene encoding the nucleocapsid (N) protein of Indiana 1 serotype vesicular
      stomatitis virus (VSV-IN1) was transferred into the genome of Autographa
      californica nuclear polyhedrosis virus (baculovirus) as a full-length non-fusion
      construct under the control of the polyhedrin gene promoter. Recombinant N
      protein was obtained from Trichoplusia ni insect larvae inoculated 72-96 h
      previously with the recombinant baculovirus. Polyclonal antibody (PAB) against
      VSV-IN1 was produced in mice using VSV-IN1 whole virus antigen concentrated from
      virus-infected cell culture fluids. The N protein and the PAB were used without
      further purification in a competitive enzyme-linked immunosorbent assay (C-ELISA)
      for detection of bovine, porcine, and equine origin serum antibodies against VSV
      IN1. A limited number of field origin, experimental, and reference VSV antisera
      were evaluated using the C-ELISA and with a standard serum neutralization (SN)
      procedure. Sensitivity of the C-ELISA was comparable to the serotypically
      homologous SN procedure. Subject to further validation, similar C-ELISA tests for
      the other VSV serotypes, used in conjunction with the test described here, may
      offer the best combination of rapidity, sensitivity, simplicity, economy, and
      laboratory biosafety of any of the methods yet developed for VSV serodiagnosis.

PMID- 8530568
TI  - Localization of foot and mouth disease virus RNA in tissue culture infected cells
      via in situ polymerase chain reaction.
AB  - Foot and mouth disease virus RNA was visualized in infected primary tissue
      culture cells by in situ PCR incorporating digoxigenin-labeled dUTP. The viral
      RNA polymerase gene was used as a target for amplification. Infected cells
      revealed cytoplasmic staining, predominantly perinuclear. The intensity of
      staining was in proportion to the degree of cytopathology observed and similar to
      the results obtained using immunoperoxidase staining. The in situ PCR technique
      for FMDV detection could be applied to formalin-fixed samples and be useful for
      the study of persistent infections.

PMID- 8530569
TI  - Detection of DNA and RNA plant viruses by PCR and RT-PCR using a rapid virus
      release protocol without tissue homogenization.
AB  - A simple, single-step plant tissue preparation protocol suitable for the
      detection of viruses by the polymerase chain reaction and reverse transcription
      polymerase chain reaction is described. The effect of buffer components and pH,
      and the incubation temperature for the release of virus from plant material was
      evaluated. A small amount of plant tissue was heated in a solution containing 100
      mM Tris-HCl, pH 7.4 or 8.4, 1 M KCl and 10 mM EDTA for 10 min at 95 degrees C and
      the supernatant used for enzymatic amplification. This protocol was suitable for
      the detection of both DNA and RNA viruses in a variety of plant species and
      tissues and reduced plant inhibitory factors which may interfere with PCR. The
      application of this method was demonstrated for the detection of banana bunchy
      top virus in banana leaves, root and corn, zucchini yellow mosaic potyvirus in
      squash leaves and lettuce necrotic yellows rhabdovirus in lettuce and Nicotiana
      glutinosa leaves.

PMID- 8530570
TI  - Detection of dengue viral RNA by microplate hybridization.
AB  - Dengue virus infection is a major public health problem throughout tropical
      countries. In endemic areas, dengue hemorrhagic fever (DHF) or dengue shock
      syndrome (DSS) are common complications resulting in death. However, serological
      confirmation of dengue-related illness is often complicated and time-consuming.
      Detection of dengue viruses in clinical or field samples usually depends on virus
      isolation in susceptible cell lines or in mosquitoes, followed by viral protein
      identification using polyclonal or monoclonal antibodies. The increasing
      incidence of dengue virus infections has prompted increased efforts to develop
      rapid and reliable diagnostic techniques. A simple microplate hybridization
      method was developed for identification of viral RNA. Microplate hybridization is
      simpler than enzyme-linked immunosorbent assay and has several advantages over
      the conventional dot-blot hybridization method: (1) radioisotopes are not
      necessary; (2) synthetic oligonucleotide for the probe is not needed; (3) the
      time required for washing of the solid phase is greatly reduced; and (4) baking
      is eliminated. The results show that this procedure is sensitive, rapid and easy
      to perform.

PMID- 8530571
TI  - Clinical review 75: Recent advances in pathogenesis, diagnosis, and management of
      acromegaly.

PMID- 8530572
TI  - Gonadotropin-releasing hormone (GnRH) agonists and estrogen/progestin replacement
      for the treatment of hirsutism: evaluating the results.

PMID- 8530573
TI  - Leuprolide and estrogen versus oral contraceptive pills for the treatment of
      hirsutism: a prospective randomized study.
AB  - The administration of long-acting GnRH analogs (GnRH-a) results in gonadotropin
      and androgen suppression in hyperandrogenic women. Nonetheless, no randomized
      studies are available comparing GnRH-a with currently used treatments for
      hirsutism. We have hypothesized that the greater degrees of androgen suppression
      achieved with GnRH-a therapy could result in a more rapid improvement in
      hirsutism compared to oral contraceptive (OCP) administration. To test this
      hypothesis, we studied 17 hirsute women before and during 6 months of randomized
      treatment with 1) leuprolide depot (3.75 mg/month) plus conjugated estrogen
      (0.625 mg/day) and medroxyprogesterone acetate (10 mg; days 1-12; n = 9;
      leuprolide+ERT), or 2) an OCP containing ethynodiol diacetate (1 mg) and ethinyl
      estradiol (35 micrograms; n = 8). LH, FSH, estradiol, dehydroepiandrosterone
      sulfate, androstenedione (A4), sex steroid-binding globulin, and total and free
      testosterone (T) were measured at weeks 0, 2, 4, 8, 12, and 28. At 0 and 28 weeks
      of treatment, hirsutism was evaluated subjectively by patient self-evaluation and
      by the Ferriman-Gallwey score, and objectively by determination of facial hair
      density, outer hair shaft diameter, and growth rate, determined both
      photographically and in plucked hairs. In the leuprolide+ERT, but not OCP,
      groups, there was a significant decrease in the circulating LH and FSH levels. In
      both groups, T and A4 decreased with treatment, although the decrease in A4
      levels did not reach significance in OCP-treated women. The circulating sex
      steroid-binding globulin level increased in both treatment groups, but the
      changes in the OCP-treated women was greater. Consequently, although the
      calculated percent free T decreased significantly in both treatment groups, the
      decrease was greater in the OCP-treated women. The dehydroepiandrosterone sulfate
      level did not change with either therapy. A significant percent decrease in the
      Ferriman-Gallwey score was noted in the leuprolide+ERT, but not OCP, patients,
      and by self-evaluation, seven (78%) and five (55%) of leuprolide+ERT patients,
      compared to two (25%) and two (25%) OCP-treated women, noted an improvement in
      hair growth and texture, respectively. No significant difference in mean facial
      hair density or outer hair diameter was noted with either therapy. Patients
      treated with leuprolide+ERT demonstrated a decrease in the actual hair growth
      rate, using the photographic method, or percent decrease in growth rate, using
      plucked hair. In conclusion, treatment with leuprolide plus cyclic
      estrogen/progestin appears to provide a more rapid, and possibly greater,
      improvement in hirsutism, compared to a standard OCP regimen.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8530574
TI  - Comparison of a gonadotropin-releasing hormone agonist and a low dose oral
      contraceptive given alone or together in the treatment of hirsutism.
AB  - Chronic GnRH agonist therapy lowers androgens and decreases androgen-dependent
      hair shaft diameter, but the resulting induction of hypoestrogenemia has limited
      its usefulness as a single agent. Estrogen- and progestin-containing oral
      contraceptives also reduce circulating androgen levels and are commonly used
      empirically for the treatment of hirsutism, but have not been evaluated in a
      blinded randomized controlled fashion. The present study is the first double
      masked trial to evaluate the combination use of a GnRH agonist and an estrogen
      containing oral contraceptive and tests our hypothesis that these could
      synergistically reduce androgen levels and suppress hormone-dependent hair growth
      while avoiding the symptoms and risks of agonist-induced hypoestrogenemia. We
      enrolled 64 women in a 24-week blinded randomized controlled trial to compare
      placebo, nafarelin (NAF; 400 micrograms, intranasal spray, twice daily),
      norethindrone (1 mg), and ethinyl estradiol (NOR 1/35; 0.035 mg, daily, for 3 of
      4 weeks), or combined use of NAF and NOR 1/35 for 24 weeks. At baseline and every
      8 weeks, we measured gonadotropins, estrogens, androgens, and hair growth. Bone
      density was assessed by dual energy x-ray adsorptiometry, and hot flashes were
      measured objectively. Baseline total testosterone (T), free T, percent free T,
      and sex hormone-binding globulin-binding capacity were similar among groups. With
      treatment, significant reductions (P = 0.01) in total T were seen with
      combination and NAF only therapy. Significant increases (P < 0.001) in the sex
      hormone-binding globulin-binding capacity were seen in women given NOR 1/35 alone
      or in combination with NAF. Free T levels decreased to approximately half of
      baseline levels with combination treatment (17.9 to 6.4 nmol/L; P < 0.001) and
      NOR 1/35 alone (20.8 to 10.2 nmol/L; P < 0.001). There was a significant decrease
      in hair shaft diameter after combination therapy (P < 0.05) that was not seen
      with either agent alone. Combination therapy also prevented the hot flashes and
      bone loss that occurred with agonist alone. In summary, our results demonstrate
      that combination GnRH agonist and low dose oral contraceptive therapy is more
      effective than either agent alone in the treatment of hirsutism and avoids the
      hypoestrogenic complications that occur with agonist only therapy.

PMID- 8530575
TI  - The immune response to papillary thyroid cancer.

PMID- 8530576
TI  - The correlation between papillary thyroid carcinoma and lymphocytic infiltration
      in the thyroid gland.
AB  - Ninety-five patients with papillary thyroid carcinoma (PTC) who received primary
      surgical treatment in 1983 at Kuma Hospital and were followed until 1992 were the
      subjects of this study. Initial therapy was tumor resection for 5 patients,
      lobectomy for 23 patients, total thyroidectomy with unilateral modified neck
      dissection for 60 patients, and total thyroidectomy with bilateral modified neck
      dissection for 7 patients. Clinical stage at diagnosis was as follows. Class I
      included 28 patients with intrathyroidal disease, class II included 60 patients
      with positive cervical lymph nodes, and class II included 7 patients with tumor
      invasion into tissue outside of the thyroid gland. Recurrence of the tumor was
      evaluated according to lymphocytic infiltration in the thyroid gland. Group A
      consisted of 36 patients with PTC associated with lymphocytic infiltration, 26
      with infiltration surrounding the tumor, 3 with infiltration inside of the tumor,
      and 7 with both. Group B consisted of the remaining 59 patients with PTC with no
      lymphocytic infiltration. There were no differences in age, sex, initial tumor
      size, or initial treatment between groups A and B. Antithyroglobulin antibody
      and/or antimicrosomal antibody were positive in 16 patients from group A and 4
      patients from group B (P < 0.001). Class I included 14 patients from each group,
      class II included 22 patients from group A and 38 patients from group B, and
      class III included 7 patients, all from group B. Recurrence of the tumor was
      found in only 1 group A patient (2.8%), but in 11 patients of group B (18.6%).
      The percentage of patients free from recurrence over the 10 yr of follow-up in
      group A was significantly higher than that in group B (by Cox-Mantel test, P <
      0.01). The time between initial treatment and recurrence was 2-10 yr. In
      comparing the clinical stage at the time of initial treatment, recurrence was
      found in 1 class II patient from group A (4.5%) and in 1 class I (7.1%), 6 class
      II (15.8%), and 4 class III (57.1%) patients from group B. No patients died
      during the 10 yr of follow-up. In conclusion, 1) lymphocytic infiltration
      surrounding the tumor or inside the tumor in PTC might be of use as a means for
      predicting a favorable prognosis; and 2) class II or class III patients with no
      lymphocytic infiltration had a high rate of recurrence.

PMID- 8530577
TI  - Gene amplification as a cause for inherited thyroxine-binding globulin excess?

PMID- 8530578
TI  - Extrathyroidal manifestations of Graves' disease.

PMID- 8530579
TI  - Immunoglobulin A class fibroblast antibodies in patients with Graves' disease and
      pretibial myxedema.
AB  - The involvement of autoantibodies in the extrathyroidal manifestations of Graves'
      disease has been the subject of extensive investigation, with fairly inconclusive
      results to date. We investigated the presence of immunoglobulin A (IgA) and IgG
      antibodies in patients with Graves' disease and pretibial myxedema (PTM; n = 21)
      as well as those with Graves' disease with thyroid-associated ophthalmopathy
      (TAO; n = 10), Graves' disease with no clinical evidence of extrathyroidal
      manifestations (n = 11), Hashimoto's thyroiditis (n = 9), type 1 diabetes
      mellitus (n = 10), systemic lupus erythematosus (n = 9) and normal individuals (n
      = 17). We looked for antibodies to both retroocular muscle and dermal fibroblasts
      as well as to thyroid peroxidase, thyroid microsomal antigen, thyroglobulin, and
      human eye muscle membranes. IgA class antibodies to microsomal antigen (30-50% of
      patients), thyroid peroxidase (5-20%), and human eye muscle membrane (0-26%)
      antigens were found in the various groups of patients with Graves' disease. With
      each of these antigens, serum from patients with PTM showed the greatest binding.
      Highly significant IgA binding was shown by PTM serum to both dermal (P < 0.001)
      and retroocular muscle (P < 0.001) fibroblasts from 12 different donors. Serum
      from Graves' patients with and without TAO and that from Hashimoto's thyroiditis
      patients reacted significantly with 4 of the 12 fibroblasts lines. In contrast,
      IgG binding was only found for 3 of the 12 fibroblast lines using patient serum.
      The IgA binding to fibroblasts shown by PTM patients was predominantly of the
      IgA2 subclass. The activity was absorbed out by both fibroblasts and thyroid
      cells. In immunoblotting studies, PTM patient serum reacted with a 54-kilodalton
      dermal fibroblast antigen and a 66-kilodalton retroocular fibroblast antigen. No
      binding to these antigens was seen with serum from normal controls or patients
      without PTM. Further elucidation of the nature of this fibroblast antigen will
      help to determine the role of IgA autoantibodies in the extrathyroidal
      manifestations of Graves' disease.

PMID- 8530580
TI  - Primary aldosteronism (Conn's syndrome).

PMID- 8530581
TI  - An unusual type of familial lipodystrophy.
AB  - A mother and her daughter with a novel type of familial partial lipodystrophy
      were studied. Both had atrophy of fat in the face, chest, and upper and lower
      limbs and abdominal obesity caused by intraabdominal fat accumulation. The mother
      had severe insulin resistance and impaired glucose tolerance, whereas the
      daughter had normal glucose tolerance and normal insulin sensitivity. Both had
      metabolic rates about 30% above normal levels, but normal thyroid function and
      plasma lipids.

PMID- 8530582
TI  - Insulin-like growth factor I receptor expression and function in fibroblasts from
      two patients with deletion of the distal long arm of chromosome 15.
AB  - Most patients with deletion of the distal long arm of chromosome 15 have
      intrauterine growth retardation and postnatal growth deficiency in addition to
      developmental abnormalities. It has been proposed that the absence of one copy of
      the insulin-like growth factor I (IGF-I) receptor gene may play a role in the
      growth deficiency seen in this syndrome. To address this question we examined IGF
      I receptor expression and function in fibroblasts from two patients with deletion
      of the distal long arm of chromosome 15 (15q26.1-->qter). Quantitative Southern
      blot analysis of the IGF-I receptor gene was performed on HindIII digests of
      fibroblast DNA. Radioactivity in the 1.7-kilobase receptor fragment in the two
      patients was 55% and 51% of the values in controls, consistent with the absence
      of one copy of the IGF-I receptor gene. IGF-I receptor messenger ribonucleic acid
      levels were quantitated by a solution hybridization/nuclease protection assay.
      Receptor messenger ribonucleic acid levels in the two patients were 45% and 52%
      of the values in controls. Northern blotting demonstrated normal size IGF-I
      receptor transcripts and affinity crosslinking of [125I]IGF-I to Triton X-100
      solubilized fibroblasts demonstrated a normal size receptor in the patients.
      Analysis of placental membranes prepared from one patient revealed no difference
      in [125I]IGF-I binding. In the patients' fibroblasts, however, binding of
      [125I]long [R3]-IGF-I to the IGF-I receptor was significantly reduced, as
      assessed by the amount of radioactivity competed by the monoclonal antibody alpha
      IR-3 or insulin and Scatchard analysis of binding data. To assess IGF-I receptor
      function, stimulation of [alpha-1-14C]-methylaminoisobutyric acid transport and
      stimulation of [methyl-3H]thymidine incorporation into DNA by a full range of IGF
      I concentrations was examined in patient and control fibroblasts. There was a
      significant decrease in the maximal response to IGF-I in both assays for one of
      the two patients when data were expressed as fold response over the basal value.
      However, there was no evidence for impairment of response to IGF-I in either
      patient's fibroblasts when data were expressed as net stimulation (maximal
      response minus basal). In conclusion, although IGF-I receptor expression was
      decreased in fibroblasts from two patients with deletion of the distal long arm
      of chromosome 15, we were unable to provide conclusive evidence for impairment of
      the biological response to IGF-I.

PMID- 8530583
TI  - Mechanism of renal calcium conservation with estrogen replacement therapy in
      women in early postmenopause--a clinical research center study.
AB  - To assess the mechanism by which estrogen replacement therapy (ERT) enhances
      renal calcium conservation in perimenopausal women, we studied 18 normal women in
      early postmenopause before and after 6 months of ERT (cyclic treatment with
      transdermal estradiol at 100 micrograms/day and medroxyprogesterone acetate at 10
      mg/day for the first 12 days of each cycle). The changes after ERT were: serum
      ionized calcium and ultrafiltrable calcium, no change; serum intact PTH, 38.2%
      increase (P < 0.0001); serum 1,25-dihydroxyvitamin D, 23.8% increase (P <
      0.0001); urinary calcium excretion, 33.3% decrease (P < 0.001); and
      deoxypyridinoline (a marker for bone resorption), 19.5% decrease (P < 0.0001).
      Also, ERT increased tubular reabsorption of calcium (TRCa; 97.6% +/- 0.2% to
      98.7% +/- 0.1%; P < 0.0001), and this increase correlated with that in serum PTH
      (r = 0.49; P < 0.05). After the infusion of human PTH-(1-34), the TRCa maximum
      was greater after ERT than at baseline (99.4% +/- 0.1% vs. 99.0% +/- 0.1%; P <
      0.0001), resulting in decreased calcium excretion (0.9 +/- 0.20 vs. 1.43 +/- 0.20
      mumol/dL glomerular filtrate; P < 0.001). Thus, in early postmenopause, the major
      mechanism of increased renal calcium conservation after ERT is an increase in
      TRCa due to an increase in serum PTH because of estrogen-induced inhibition of
      bone resorption. However, ERT also may directly increase the TRCa maximum in
      response to PTH.

PMID- 8530584
TI  - Skeletal metabolism in patients with osteoporosis after discontinuation of long
      term treatment with oral pamidronate.
AB  - Bisphosphonates are used with increasing frequency in the treatment of patients
      with osteoporosis. Continuous administration of low doses of nitrogen-containing
      bisphosphonates by mouth is the preferred mode of therapy. The skeletal half-life
      of bisphosphonates is long, however, and little is known about their long term
      effects on skeletal metabolism. We examined the changes in biochemical parameters
      of bone turnover [serum alkaline phosphatase and urinary hydroxyproline (OHP)],
      in bone mineral density, and in fracture frequency after discontinuation of long
      term (mean, 6.5 yr, range, 5-9 yr) therapy with oral pamidronate (150 mg/day) in
      30 patients with osteoporosis and vertebral fractures. Serum alkaline phosphatase
      and urinary OHP were significantly lower at the end of long term treatment (90%
      and 72% of basal values, respectively). Serum alkaline phosphatase had increased
      to basal values within 6 months of stopping treatment, whereas OHP increased
      significantly to a maximum average of 92% of pretreatment values. There was no
      change in the every 6-month bone mineral density measurements of the lumbar spine
      and the femoral neck during the 2 yr after stopping treatment. Spine fracture
      index, calculated by the method of Raymakers and co-workers, was 0.83 +/- 0.12
      before treatment, 0.85 +/- 0.12 at the end of treatment, and 0.85 +/- 0.13 2 yr
      after stopping treatment (nonsignificant). There was also no significant change
      in the rate of new vertebral fractures on or up to 2 yr after stopping treatment
      (48.5 of 1000 and 46.5 of 1000 patient yr, respectively). Our data demonstrate
      that the sustained suppression of bone turnover induced by long term treatment
      with pamidronate is readily reversible on stopping treatment. The beneficial
      effect of this treatment regimen on the skeleton, however, appears to be
      maintained for at least 2 yr after discontinuation of treatment.

PMID- 8530585
TI  - Body fat distribution and steroid hormone concentrations in obese adolescent
      girls before and after weight reduction.
AB  - The aim of this study was to investigate the role of body fat distribution on
      steroid hormone serum concentrations in obese adolescent girls before and after
      weight reduction. Ninety-two girls (age, 15.1 +/- 0.7 yr) with a mean body mass
      index of 31.2 +/- 4.6 kg/m2 participated in this 6-week intervention study.
      Initially, girls with abdominal obesity (waist to hip ratio, > 0.86; n = 30) had
      higher levels of total and free testosterone and lower levels of sex hormone
      binding globulin as well as lower morning levels of total and free cortisol than
      girls with gluteal-femoral obesity (waist to hip ratio, < 0.80; n = 31)
      independent of their body mass index. After a mean weight loss of 8.3 +/- 2.6 kg
      by a standardized weight loss program, significant reductions were observed in
      estradiol, total and free testosterone, dehydroepiandrosterone sulfate, and the
      ratio of LH to FSH, whereas sex hormone-binding globulin and free cortisol levels
      increased significantly. Decreases in total and free testosterone and increases
      in total and free cortisol were significantly greater in the girls with abdominal
      obesity than in the girls with gluteal-femoral obesity. Our results suggest that
      obese girls with an abdominal pattern of fat distribution exhibit more pronounced
      steroid hormone aberrations, in particular a high androgenic activity, than girls
      with a gluteal-femoral pattern of fat distribution. The reduction of excess body
      weight by a conventional treatment regimen is associated with a remarkable
      improvement of steroid hormone abnormalities in this particular subtype of obese
      adolescent girls.

PMID- 8530586
TI  - Proliferation of cultured human prostate cancer cells is inhibited by insulin
      like growth factor (IGF) binding protein-1: evidence for an IGF-II autocrine
      growth loop.
AB  - In this study, we examined the expression of insulin-like growth factor (IGF)
      ligands, receptors, (IGFR1, IGFR2), and binding proteins (IGFBPs) in the human
      prostate cancer cell line DU145, as well as its mitogenic response to the IGFs.
      Using RNase protection assays, we found expression of IGF-II, IGFR1, and IGFR2
      but failed to detect IGF-I messenger RNA. Distinct binding protein species as
      well as immunoreactive IGF-II were detected in conditioned media using
      radioligand and immunoblotting assays. Compared with controls, treatment with
      exogenous IGF-I and IGF-II resulted in stimulation of monolayer and anchorage
      independent growth. Recombinant human IGFBP-1, which binds IGF-II with high
      affinity, inhibited IGF-II-induced monolayer growth and both baseline and IGF-II
      induced anchorage-independent growth in this cell line. Our data suggest IGF-II
      is as an autocrine growth factor in DU145 cells, and that inhibition of IGF-II
      dependent growth of human prostate cancer cells may represent a new therapeutic
      strategy for this disease.

PMID- 8530587
TI  - Expression of functional growth hormone receptors in cultured human osteoblast
      like cells.
AB  - Recent clinical studies indicate that GH is important for bone remodeling.
      Patients with GH deficiency exhibit decreased bone density, and GH substitution
      increases bone density in these patients. The aim of the present study was to
      investigate the presence of GH receptors and the effects of GH on cultured human
      osteoblast-like cells. Primary cultures of human osteoblast-like cells were
      established from trabecular bone. Northern blot analysis, using a probe
      recognizing exon 10 of the human GH receptor, revealed a 4.7-kilobase transcript
      corresponding to the human GH receptor. Cultured osteoblast-like cells expressed,
      as determined by RNase protection assay, approximately one fourth of the GH
      receptor messenger RNA levels found in liver. Binding studies using 125I-labeled
      GH revealed a single class of receptors with approximately 2000 binding sites per
      cell and an association constant (Ka) of 2.6 x 10(9) M-1. GH stimulation of the
      cultured cells resulted in increased [3H]thymidine incorporation, suggesting that
      the GH receptors are functional. In summary, the present study shows that
      cultured human osteoblast-like cells express functional GH receptors.

PMID- 8530588
TI  - Accumulation of 5 alpha-reduced androgen glucosiduronates associated with
      impaired removal in young male hemodialysis patients.
AB  - Hypothalamic-pituitary gonadal function is commonly altered in dialysis patients.
      Even though an improvement in general status and well-being has been noted after
      recombinant human erythropoietin supplementation, no significant changes were
      observed in the sex hormone profile. Pituitary gonadal axis as well as 5 alpha
      reduced androgen glucosiduronates (i.e. 5 alpha-androstane,3 alpha,17 beta-diol
      and androsterone) profiles were studied in 23 young male stable dialyzed patients
      and compared to an age-matched group of healthy subjects. 5 alpha-Reduced
      androgen glucosiduronates are products of peripheral testosterone (T) metabolism
      and seem to be a useful tool in assessment of the male androgen status. Their
      polarity facilitates their urinary excretion, and their clearance is similar to
      the glomerular filtration rate in healthy men. We observed 1) a pituitary-Leydig
      cell dysfunction supported by normal serum estradiol and T levels, low free T,
      and increased LH levels; 2) an alteration of the dehydroepiandrosterone (DHEA)
      sulfate-DHEA interconversion, reflected by a dramatic decrease in DHEA while DHEA
      sulfate levels remained in the normal range; 3) an accumulation of 5 alpha
      reduced androgen glucosiduronates, whose removal was impaired as shown by their
      very low sieving coefficients (< 0.012). Taken together, the above observations
      are consistent with alteration of spermatogenesis with respect to dialysis
      duration in which earlier elevated baseline serum LH levels indicate a primary
      defect in Leydig cell function.

PMID- 8530589
TI  - Mutated human androgen receptor gene detected in a prostatic cancer patient is
      also activated by estradiol.
AB  - Androgens are necessary for the development of prostatic cancer. The mechanisms
      by which the originally androgen-dependent prostatic cancer cells are relieved of
      the requirement to use androgen for their growth are largely unknown. The human
      prostatic cancer cell line LNCaP has been shown to contain a point mutation in
      the human androgen receptor gene (hAR), suggesting that changes in the hAR may
      contribute to the abnormal hormone response of prostatic cells. To search for
      point mutations in the hAR, we used single strand conformation polymorphism
      analysis and a polymerase chain reaction direct sequencing method to screen 23
      prostatic cancer specimens from untreated patients, 6 prostatic cancer specimens
      from treated patients, and 11 benign prostatic hyperplasia specimens. One
      mutation was identified in DNA isolated from prostatic cancer tissue, and the
      mutation was also detected in the leukocyte DNA of the patient and his offspring.
      The mutation changed codon 726 in exon E from arginine to leucine and was a germ
      line mutation. The mutation we found in exon E of the hAR gene does not alter the
      ligand binding specificity of the AR, but the mutated receptor was activated by
      estradiol to a significantly greater extent than the wild-type receptor. The AR
      gene mutation described in this study might be one explanation for the altered
      biological activity of prostatic cancer.

PMID- 8530590
TI  - Evidence of a distinct derangement of opioid tone in hyperinsulinemic patients
      with polycystic ovarian syndrome: relationship with insulin and luteinizing
      hormone secretion.
AB  - Recent data indicate that an altered opioid tone could be involved in the LH
      hypersecretion and metabolic alterations seen in polycystic ovary syndrome
      (PCOS). The aim of the present study was to investigate the presence of a common
      mechanism of action of opioids on altered insulin and gonadotropin release in
      patients suffering from PCOS. Twenty-eight women affected by PCOS and 8 normal
      ovulatory women were studied; an oral glucose tolerance test (OGTT) and GnRH
      tests were performed during the follicular phase before and after 6 weeks of
      naltrexone treatment (50 mg/day, orally). Plasma levels of sex hormone-binding
      globulin and steroids were assayed in the basal samples, whereas FSH and LH were
      analyzed during the GnRH stimulus. Insulin and glucose were assayed by the OGTT.
      Based on the insulinemic response to OGTT, 17 women were classified as
      hyperinsulinemic and 11 as normoinsulinemic. No difference in glucose and hormone
      plasma concentrations was observed before and after naltrexone treatment in both
      groups. Only basal sex hormone-binding globulin values were higher in
      normoinsulinemic compared to hyperinsulinemic subjects. Administration of the
      opioid antagonist significantly reduced the insulin response to OGTT only in the
      hyperinsulinemic group. No difference were found in the LH increment after the
      GnRH stimulus in both group of patients before treatment; on the contrary,
      naltrexone administration reduced the LH response to GnRH in hyperinsulinemic
      women but failed to be effective in normoinsulinemic subjects. Only 5 patients
      showed no concordance of drug-induced changes in insulin and LH secretion. In
      control subjects, naltrexone failed to have any effect on insulin or LH
      secretion. These data support the involvement of endogenous opioids in the
      regulation of insulin and LH secretion in a specific group of PCOS patients
      exhibiting an exaggerated insulin response to OGTT.

PMID- 8530591
TI  - Dynamics of prolactin secretion in patients with hypopituitarism and pituitary
      macroadenomas.
AB  - Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in
      patients with pituitary macroadenomas that do not secrete PRL. We postulated that
      hypopituitarism in this setting, is primarily caused by compression of the portal
      vessels and/or pituitary stalk. If this were the case, the dynamics of PRL
      secretion in this instance would be similar to those in patients with stalk
      section, dopamine deficiency, or hypothalamic disease. Furthermore, as
      hypopituitarism in this setting is largely reversible, we postulate that PRL
      dynamics should also normalize after adenomectomy as a result of the resumption
      of hypothalamic regulation of pituitary hormone secretion. To test these
      hypotheses, we examined PRL responsiveness to TRH and the dopamine antagonist,
      perphenazine (PZ), in patients with pituitary macroadenomas who had
      hypopituitarism and others with intact pituitary function (controls). Dynamic
      studies were performed before and 2-3 months after total or subtotal
      adenomectomy, and the results were correlated with alterations in other pituitary
      function. In addition, plasma ACTH, cortisol, and PRL levels were measured hours
      to days after surgery to investigate immediate alterations in pituitary function
      following surgical decompression. Before surgery, hypopituitary patients had
      higher serum PRL level than controls (25.5 +/- 12 vs. 11 +/- 3 micrograms/L; P <
      0.001). Preoperative dynamic testing of PRL secretion in hypopituitary patients
      demonstrated an increase in PRL levels after TRH, but not after PZ,
      administration. In contrast, PRL levels increased appropriately when either
      stimulus was given to controls. Hours after adenomectomy, PRL levels decreased by
      50% in hypopituitary patients (P < 0.0001) and remained so until discharge. In
      contrast, controls had a transient increase in serum PRL levels after
      adenomectomy. After surgery, 25 of 43 previously hypopituitary patients recovered
      part or all pituitary function. Serum PRL levels in the latter subgroup became
      normal and increased appropriately after stimulation with either TRH or PZ. In
      contrast, patients who did not recover pituitary function had lower PRL levels
      that increased minimally after TRH or PZ. The mild increase in serum PRL levels
      in hypopituitary patients and the discordant responses to stimulation with TRH
      and PZ suggest dopamine deficiency as a cause of hyperprolactinemia. The drop in
      serum PRL levels immediately after surgery, at a time when other pituitary
      hormones (e.g. ACTH), were documented to rise suggests restoration of
      hypothalamic control over pituitary hormone secretion. The pattern of PRL
      responses to stimulation in patients recovering function postoperatively was
      similar to that in controls, although the incremental rise was
      subnormal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8530592
TI  - Thyroid epithelial cells produce large amounts of the Alzheimer beta-amyloid
      precursor protein (APP) and generate potentially amyloidogenic APP fragments.
AB  - The Alzheimer beta-amyloid precursor protein (APP) is a transmembrane
      glycoprotein from which the amyloid beta-protein is proteolytically derived. The
      latter is a hydrophobic peptide that can aggregate and forms the core of the
      senile plaques found in the brains of patients suffering from Alzheimer's disease
      (AD). In view of the known association between familial AD and thyroid autoimmune
      disease, the expression pattern and cellular processing of APP in human thyroid
      cells were investigated. Cultured thyroid epithelial cells and homogenized
      thyroid tissue from normal and pathological thyroid samples were analyzed by
      immunoblotting using specific N- and C-terminal APP antibodies as well as by
      reverse transcription-polymerase chain reaction in which two sets of
      oligonucleotide primers were used. The results of these studies demonstrated that
      APP isoforms 770 and 751 were expressed in fresh thyroid extracts as well as in
      cultured thyroid epithelial cells, with APP 770 being the predominant form.
      Compared to other types of cells, such as lymphocytes and fibroblasts, thyroid
      epithelial cells produced larger amounts of APP. Most of the mature protein was
      cleaved within the amyloid beta region, as a result of which a large N-terminal
      APP fragment was released into the culture medium, whereas a C-terminal
      nonamyloidogenic fragment of 14 kilodaltons (kDa) was retained within the cell.
      Interestingly, thyroid epithelial cells also contained larger C-terminal APP
      fragments of 21, 35, and 41 kDa. From the sizes of these fragments it could be
      deduced that they contained the entire amyloid beta sequence and were thus
      potentially amyloidogenic. The 41-kDa fragment was unique to thyroid cells. These
      fragments may be released into the circulation after thyroid cell damage.
      Increased/altered thyroid APP expression in familiar AD may induce alterations in
      thyroid epithelial cells and cell damage, and thus explain the frequent
      occurrence of thyroid autoimmunity in this disease.

PMID- 8530593
TI  - Hormonal regulation of circulating insulin-like growth factor-binding protein-1
      phosphorylation status.
AB  - Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) normally circulates
      as a single, highly phosphorylated species. However, IGFBP-1 phosphorylation
      status can be altered, such as in pregnancy where non- and lesser phosphorylated
      isoforms are also present. We have examined how hormonal regulators of
      circulating IGFBP-1 influence its phosphorylation status and, hence, its ability
      to modulate IGF activity. In response to insulin-induced hypoglycemia (0.2 U/kg,
      iv), an increase in the highly phosphorylated isoform was observed after 5 h [16
      (range, 11.5-35.5) to 77 (range, 63-250) microgram/L; 4.8-fold increase; P =
      0.009], but no non- or lesser phosphorylated variants could be detected. Glucagon
      (1 mg, sc), increased IGFBP-1 from 27 (range, 13-36.5) to 112 (range, 100.5-129)
      micrograms/L (4.1-fold increase; P = 0.009) after 90 min despite preceding
      insulin concentrations of more than 500 pmol/L, but again the IGFBP-1 remained in
      the highly phosphorylated form. Regulation of IGFBP-1 phosphorylation by sex
      steroids was studied by comparing women receiving a combined oral contraceptive
      with women on no medication. Although plasma IGFBP-1 levels were significantly
      elevated in the treatment group [120 (range, 97.5-237.5) vs. 52 (range, 38-70)
      micrograms/L; P < 0.004], there was no difference in the form of IGFBP-1 present.
      The acute effect of somatostatin (500 micrograms/h) on IGFBP-1 phosphorylation
      status was also studied. Somatostatin only increased the phosphoform
      characteristic of normal subjects; the appearance of non- or lesser
      phosphorylated variants was not induced. The effect of rhIGF-I (80 or 120
      micrograms, sc) on plasma IGFBP-1 was studied in three subjects with Laron's
      syndrome. A transient increase in the highly phosphorylated isoform of IGFBP-1
      was noted; there was no rise in the non- and lesser phosphorylated isoforms also
      found in the plasma of Laron's syndrome subjects. These data suggest that only
      the highly phosphorylated species of IGFBP-1 is under hormonal control;
      regulation of the non- and lesser phosphorylated variants remains to be
      determined.

PMID- 8530594
TI  - High maternal serum chorionic gonadotropin level in Downs' syndrome pregnancies
      is caused by elevation of both subunits messenger ribonucleic acid level in
      trophoblasts.
AB  - A unique product of human placenta is CG. Its concentration in maternal blood
      rises exponentially until 9-10 weeks' gestation, thereafter, it decreases to
      about 20% of the maximum, remaining constant from 16-17 until 40 weeks. High
      second-trimester maternal blood level indicates an increased risk for Downs'
      Syndrome (DS). This study's aim was to determine whether changes occur in the
      genetic expression of CG subunits in cultured trisomy-21 trophoblasts compared
      with various gestational age controls. Second-trimester trisomy-21 trophoblasts
      secrete 10 times more CG than gestational age-matched controls during the first
      day in culture: 878 (range, 235-2230) IU/g vs. 87 (range, 20-150) IU/g (P <
      0.05). This high secretion closely resembles quantities secreted by first
      trimester normal trophoblasts: 7500 (range, 3,850-10,000) IU/g. Both subunits'
      messenger RNA content are substantially increased, CG beta much more than CG
      alpha, although these genes are not located on chromosome 21. We conclude that at
      least one cause of high second-trimester maternal blood CG in DS pregnancies is a
      rise in alpha and beta CG messenger RNA levels in the trophoblast. We propose
      that at 12-14 weeks, when rapid decrease in maternal blood CG levels can be
      found, higher than normal values may indicate an increased risk for DS.

PMID- 8530595
TI  - Nested polymerase chain reaction study of 53 cases with Turner's syndrome: is
      cytogenetically undetected Y mosaicism common?
AB  - Turner's syndrome patients with Y mosaicism face a high risk of developing
      gonadoblastoma. Cytogenetic analysis can fail to detect rare cells bearing a
      normal or structurally abnormal Y chromosome (low level Y mosaicism). We screened
      53 individuals with Turner's syndrome for presence of sex-determining region Y
      (SRY), the testis-specific protein, Y encoded, gene, and the Y centromeric DYZ3
      repeat using nested polymerase chain reaction (PCR). Thirty girls (57%) had the
      45,X karyotype, determined through standard analysis of blood lymphocytes. The
      remaining 23 girls (43%) were mosaics and/or had structural abnormalities in 1 X
      chromosome. Genomic DNA from blood leukocytes was amplified using 2 rounds of
      PCR. This method was sensitive enough to detect 0.0001% male DNA on a female
      background. None of 53 Turner's syndrome cases was positive for Y-specific loci
      after the first round of PCR. After the second round, 2 of 53 Turner's syndrome
      cases were positive for SRY mapping to the distal short arm of chromosome Y. In 1
      SRY-positive subject, the karyotype was 45,X, and in the other, it was 46,Xi(Xq).
      None of 53 Turner's syndrome individuals, including the 2 SRY-positive subjects,
      were positive for the testis-specific protein, Y encoded, gene on the proximal
      short arm of chromosome Y or the centromeric DYZ3 repeat. These data exclude low
      level Y mosaicism in almost all Turner's syndrome cases tested.

PMID- 8530596
TI  - The endocrinology of the menopausal transition: a cross-sectional study of a
      population-based sample.
AB  - In a study of the endocrinology of the perimenopausal years, levels of serum FSH,
      estradiol (E2), immunoreactive inhibin (INH), testosterone, and sex hormone
      binding globulin were measured in a population-based sample of 380 women (mean
      age, 49.4 yr; range, 45.6-56.9 yr). Subjects were divided into women who reported
      continuing regular menstrual cycles (27%; group I), a change in menstrual flow
      without a change in frequency (23%; group II), a change in frequency but no
      change in flow (9%; group III), changes in both frequency and flow (28%; group
      IV), and at least 3 months since their last menstrual period (13%; group V).
      After adjusting for age and body mass index, the geometric mean FSH increased
      across menstrual groups and, compared with group I, was 53% higher in group IV (P
      < 0.0005) and 253% higher in group V (P < 0.0001). Age- and body mass index
      adjusted geometric means for E2 and INH in group V were 54% and 53% of those in
      group 1, respectively (P < 0.005, P < 0.0001). Women in group V who did not have
      a menstrual period in the next year had higher FSH and lower E2 and INH levels
      than those who subsequently went on to have at least one more menstrual period (P
      < 0.05). FSH was negatively correlated with E2 (r = -0.30) and INH (r = -0.39),
      whereas INH was positively correlated with E2 (r = 0.45). We conclude that an
      increase in serum FSH and decreases in E2 and INH are the major endocrine changes
      associated cross-sectionally with the menopausal transition.

PMID- 8530597
TI  - Effect of raising endogenous testosterone levels in impotent men with secondary
      hypogonadism: double blind placebo-controlled trial with clomiphene citrate.
AB  - Secondary hypogonadism is not an infrequent abnormality in older patients
      presenting with the primary complaint of erectile dysfunction. Because of the
      role of testosterone in mediating sexual desire and erectile function in men,
      these patients are usually treated with exogenous testosterone, which, while
      elevating the circulating androgens, suppresses gonadotropins from the
      hypothalamic-pituitary axis. The response of this form of therapy, although
      extolled in the lay literature, has usually not been effective in restoring or
      even improving sexual function. This failure of response could be the result of
      suppression of gonadotropins or the lack of a cause and effect relationship
      between sexual function and circulating androgens in this group of patients.
      Further, because exogenous testosterone can potentially increase the risk of
      prostate disease, it is important to be sure of the benefit sought, i.e. an
      increase in sexual function. In an attempt to answer this question, we measured
      the hormone levels and studied the sexual function in 17 patients with erectile
      dysfunction who were found to have secondary hypogonadism. This double blind,
      placebo-controlled, cross-over study consisted of treatment with clomiphene
      citrate and a placebo for 2 months each. Similar to our previous observations,
      LH, FSH, and total and free testosterone levels showed a significant elevation in
      response to clomiphene citrate over the response to placebo. However, sexual
      function, as monitored by questionnaires and nocturnal penile tumescence and
      rigidity testing, did not improve except for some limited parameters in younger
      and healthier men. The results confirmed that there can be a functional secondary
      hypogonadism in men on an out-patient basis, but correlation of the hormonal
      status does not universally reverse the associated erectile dysfunction to
      normal, thus requiring closer scrutiny of claims of cause and effect
      relationships between hypogonadism and erectile dysfunction.

PMID- 8530598
TI  - Prostaglandin E2 alters human orbital fibroblast shape through a mechanism
      involving the generation of cyclic adenosine monophosphate.
AB  - Orbital fibroblasts from patients with Graves' ophthalmopathy, when treated with
      prostaglandin E2 (PGE2), become stellate and develop prominent cellular
      processes. In this paper, we describe results of studies designed to characterize
      the action of PGE2 on orbital fibroblast shape changes in vitro. Orbital and
      dermal fibroblasts were incubated with PGE2, one of several prostanoid analogues,
      8-br-cAMP or forskolin and were then visualized by phase-contrast microscopy.
      Other studies involved seeding cells in special chambers equipped with electrodes
      for cell sensing using electric cell-substrate impedance sensing (ECIS) to detect
      changes in shape. PGE2 (10(-7) mol/L) elicited a rapid and dramatic alteration in
      the shape of orbital fibroblasts but not those derived from the skin. Cells
      became stellate and developed prominent cytoplasmic processes that extended out
      from the central area containing the cell nucleus. The effects were
      stereoselective in that a number of structurally related compounds, including
      Sulprostone, PGI2, PGF2 alpha, thromboxane A2, thromboxane B2, and 11 deoxy,16,16
      dimethyl PGE2 failed to elicit a similar shape change. Butaprost (10(-5) mol/L),
      a specific EP2 agonist, elicited a similar shape-change as that observed with
      PGE2. 16,16-dimethyl PGE2, a nonselective agonist, could mimic the action of
      PGE2. The effect of PGE2 was apparent at 10(-8) mol/L, maximal at a concentration
      of 10(-7) mol/L and took 4-8 hr to evolve completely. Cycloheximide (10
      micrograms/mL) and actinomycin D (1 micrograms/mL) failed to block the shape
      change. The morphologic change could be reproduced by addition of 8-br-cAMP (3
      mmol/L) and by forskolin (5 mumol/L). Moreover, PGE2 and Butaprost treatment
      elicited in orbital cultures a massive increase in endogenous cAMP production
      while analogues not affecting cell shape failed to influence cyclic nucleotide
      generation. Three strains of orbital fibroblasts from patients with Graves'
      ophthalmopathy and three from normal orbits were tested and all responded to PGE2
      (10(-7) mol/L). Four strains of dermal fibroblasts failed to respond to PGE2. The
      changes in orbital fibroblast morphology were accompanied by a marked decrease in
      monolayer impedance as assessed by electric cell-substrate impedance sensing. The
      earliest effects were apparent within 30 min using this sensitive technique. The
      widely recognized roles of PGE2 and related compounds in the mediation of the
      inflammatory response make our current findings in orbital fibroblasts of
      potential importance to the pathogenesis of Graves' ophthalmopathy.

PMID- 8530599
TI  - Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired
      child development?
AB  - Women with antibodies against the enzyme thyroid peroxidase [TPO-Ab; formerly
      microsomal antibodies (MsAb)] are at particular risk for developing postpartum
      thyroid dysfunction; the latter is significantly associated with postpartum
      depression. Although the negative effect of postpartum maternal depression on
      child development is well documented, the consequences of elevated titers of TPO
      Ab during pregnancy and subsequent postpartum thyroid dysfunction on child
      development are not known. In a prospective study of a cohort of 293 pregnant
      women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and
      depression was investigated. Five years after delivery, child development was
      assessed in 230 children of the original cohort using the Dutch translation of
      the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during
      late gestation (n = 19, with normal thyroid function) had significantly lower
      scores (by t test) on the McCarthy Scales of Children's Abilities than antibody
      negative women. The difference on the General Cognitive Scale, which reflects IQ
      scores, was substantial (10.5 points; t = 2.8; P = 0.005). After correction for
      possibly confounding variables, maternal TPO-Ab during gestation was found to be
      the most important factor related to the scores on the General Cognitive Scale
      (odds ratio = 10.5; 95% confidence interval = 3-34; P = 0.003). We conclude that
      children of pregnant women who had elevated titers of TPO-Ab but normal thyroid
      function are at risk for impaired development.

PMID- 8530600
TI  - Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin
      in hypogonadal men: comparison to testosterone enanthate--a clinical research
      center study.
AB  - We studied and compared the pharmacokinetics and bioefficacy of two doses of
      sublingual testosterone cyclodextrin (SLT; 2.5 and 5.0 mg, administered three
      times per day) with testosterone enanthate (TE; 200 mg) given once every 20 days
      by im injections over a 60-day study period in 63 hypogonadal men. After SLT
      administration, serum testosterone (T) levels peaked at 20 min and then fell,
      reaching baseline levels by 360 min. The calculated half-lives were 60.3 +/- 7.5
      and 68.8 +/- 5.0 min after a single dose of 2.5 and 5.0 mg SLT, respectively. The
      mean area under curve (AUC) of serum T was computed over 20-day periods for the 3
      treatment groups. The mean net AUC of serum T after TE administration was about 4
      and 2-fold higher than that in the 2.5 and 5 mg groups over the last 20 days.
      Serum estradiol and dihydrotestosterone followed the same pattern as serum T.
      Serum estradiol to T ratios decreased after T replacement in all 3 groups,
      whereas serum dihydrotestosterone to T ratios were not significantly changed by T
      treatment. Suppression of serum LH and FSH levels was more marked in the patients
      treated with TE than in those given SLT. Similarly, serum sex hormone-binding
      globulin levels showed significant decreases with androgen replacement only in
      the TE and SLT 5.0 mg range groups. There were no significant adverse effects
      based on comprehensive physical examinations, urea, electrolytes, and renal or
      liver function tests. Hematocrit levels increased in the TE-treated group, but
      remained slightly lower than baseline levels in the SLT groups. Serum high
      density lipoprotein cholesterol showed a small, but significant, decrease with
      time of treatment in all groups. Despite the differences in the AUC of serum T
      levels achieved by different androgen replacement therapies, all patients showed
      significant improvements in sexual motivation and performance, with no
      significant difference between the treatment groups. We conclude that SLT may be
      a useful addition to the currently available injectable and transdermal delivery
      systems for treatment of hypogonadal men. Because of the ease of administration,
      rapid reversibility of effects, and lower AUC of serum T levels achieved compared
      to those of TE injections, SLT may be especially suitable for treatment of boys
      with delayed puberty and older men with androgen deficiency.

PMID- 8530601
TI  - Urinary cyclic adenosine 3',5'-monophosphate response in McCune-Albright
      syndrome: clinical evidence for altered renal adenylate cyclase activity.
AB  - The recent finding of an activating mutation in the Gs alpha protein, the protein
      that couples receptors to stimulation of adenylate cyclase, from endocrine and
      nonendocrine tissues of patients with McCune-Albright syndrome (MAS) suggests
      that alterations in adenylate cyclase activity may account for the clinical
      abnormalities in these patients. Many patients with MAS have hypophosphatemia.
      This may result from the presence of the activating Gs alpha mutation in proximal
      renal tubules or the elaboration of a phosphaturic factor from fibrous dysplasia.
      We, therefore, sought to characterize renal cAMP generation and phosphate
      handling in MAS patients. Intravenous infusion of PTH is a classic clinical test
      used to evaluate hormonal responsiveness of renal proximal tubule adenylate
      cyclase and examine PTH-dependent phosphate clearance. We performed PTH infusion
      in 6 MAS patients, 10 normal subjects, and 6 patients with
      pseudohypoparathyroidism (PHP). The basal urinary cAMP (UcAMP) level in the MAS
      group [5.5 +/- 2.6 nmol/dL glomerular filtration (GF)] was elevated (P < 0.05)
      compared to those in both normal subjects (3.2 +/- 1.2 nmol/dL GF) and patients
      with PHP (1.9 +/- 0.6 nmol/dL GF). However, PTH-stimulated peak UcAMP (15.0 +/-
      7.0 nmol/dL GF) and the peak/basal UcAMP ratio (3.1 +/- 1.7) in MAS were
      significantly lower than the respective values in normal subjects (30.8 +/- 16.9
      nmol/dL GF and 9.3 +/- 2.9; P < 0.05 for both) and were statistically similar to
      the blunted levels in PHP (respectively, 3.1 +/- 1.5 nmol/dL GF and 2.0 +/- 1.7).
      By contrast, the PTH-induced phosphaturic response in MAS patients was similar to
      that in the normal subjects. Our study provides clinical evidence that MAS
      patients have altered renal adenylate cyclase activity, manifested by an elevated
      basal UcAMP, but a blunted UcAMP response to PTH stimulation. These observations
      are presumably due to a mutation in the Gs alpha protein in the renal tubules.
      Despite the blunted UcAMP excretion, the phosphaturic response to PTH in MAS
      patients is intact.

PMID- 8530602
TI  - Growth hormone-binding protein in human lymph.
AB  - The high affinity GH-binding protein (GHBP) is a soluble circulating ectodomain
      of the GH receptor (GHR). In humans, it is thought to be released from the plasma
      membrane-bound GHR by proteolysis at or near the transmembrane domain. GHBP
      modulates GH action by 1) intravascular complex formation, and 2) competing with
      the GHR for ligand in tissues (interstitial complex formation). Little is known
      about the tissue source(s) of GHBP, the local regulation of GHBP generation, or
      its concentration in the interstitium. To begin addressing these questions, we
      studied GHBP levels in peripheral lymph, whose composition approximates that of
      interstitial fluid. Lymph was collected in 13 healthy adult men from cannulated
      lymphatic vessels in the calf. Venous and arterial blood samples were collected
      from the femoral vein and radial artery contemporaneously with lymph collection.
      Potential GHBP production by endothelial or blood cells was assessed by examining
      conditioned medium from in vitro cell cultures. GHBP activity was measured by
      standardized GH binding/column chromatography assay. GHBP was consistently and
      significantly lower in lymph (mean +/- SD, 4.6 +/- 1.2% GH bound/200 microL) than
      in venous (14.1 +/- 3.0%) or arterial (14.9 +/- 3.6%) plasma. Conditioned medium
      from endothelial or blood cell cultures did not contain detectable GHBP. We
      conclude that the level of GHBP in peripheral lymph is substantially lower than
      that in the peripheral circulation, and that components of the vasculature are
      not important sources of GHBP. These findings suggests that 1) the main tissue
      sources of GHBP in man are the central organs (especially liver); and 2)
      transcapillary diffusion of GHBP into the interstitial space is restricted.

PMID- 8530603
TI  - Quality of life in adults with growth hormone (GH) deficiency: response to
      treatment with recombinant human GH in a placebo-controlled 21-month trial.
AB  - We examined the effect of GH supplementation on the psychological capacity and
      sense of well-being in 36 patients with adult-onset GH deficiency (GHD).
      Recombinant human GH was given in a 21-month cross-over, double blind trial, and
      quality of life was assessed by using three self-rating questionnaires: the
      Hopkins Symptom Check List (HSCL), the Nottingham Health Profile (NHP), and the
      Psychological General Well-Being index. In addition, at the final examination the
      spouses completed a short questionnaire concerning their partner. Before
      treatment, the patients had lowered quality of life as determined by the HSCL and
      NHP inventories, and a correlation between the duration of GHD and the reported
      symptoms was observed. Upon treatment, the HSCL score was lower (better) after
      placebo administration (mean +/- SD, 84 +/- 21.3) than at baseline (89 +/- 18.9;
      P = NS) and fell to 80.2 +/- 18.5 (P < 0.001) when active drug was given. The
      subscales regarding anxiety, fearfulness, and cognition were the most sensitive.
      It was apparent that the effect determined after GH therapy in part was due to a
      placebo effect. With NHP, the dimensions of energy and emotions responded most to
      treatment. Further, the spouses observed their partners to be improved in several
      aspects of mood and behavior (P < 0.05 to P < 0.0001) when active drug was given.
      The data thus demonstrate that GH, which is known to have multiple somatic
      effects, produces an improvement in the quality of life of adults with GHD.

PMID- 8530604
TI  - A recurring dominant negative mutation causes autosomal dominant growth hormone
      deficiency--a clinical research center study.
AB  - Familial isolated GH deficiency type II (IGHD-II) is an autosomal dominant
      disorder that has been previously shown in some patients to be caused by
      heterogeneous GH gene defects that affect GH messenger RNA (mRNA) splicing. We
      report here our finding of multiple G-->A transitions of the first base of the
      donor splice site of IVS 3 (+ 1G-->A) in IGHD II subjects from three nonrelated
      kindreds from Sweden, North America, and South Africa. This + 1G-->A substitution
      creates an NlaIII site that was used to demonstrate that all affected individuals
      in all three families were heterozygous for the mutation. To determine the effect
      of this mutation on GH mRNA processing, HeLa cells were transfected with
      expression plasmids containing normal or mutant + 1G-->A alleles, and
      complementary DNAs from the resulting GH mRNAs were sequenced. The mutation was
      found to destroy 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 from the mutant
      GH mRNA. Our finding of exon 3 skipping in transcripts of the + 1G-->A mutant
      allele is identical to our previous report of a different sixth base transition
      (+6T-->C) mutation of the IVS 3 donor splice site that also causes IGHD II.
      Microsatellite analysis of an affected subjects' DNA from each of the three
      nonrelated kindreds indicates that the + 1G-->A mutation arose independently in
      each family. Finding that neither grandparent has the mutation in the first
      family suggests that it arose de novo in that family. Our data indicate that 1) +
      1G-->A IVS 3 mutations perturb GH mRNA splicing and cause IGHD II; and 2) these
      mutations can present as de novo GHD cases.

PMID- 8530605
TI  - Adult height in short normal adolescent girls treated with gonadotropin-releasing
      hormone analog and growth hormone.
AB  - GnRH analog associated with GH therapy has potential importance for treatment of
      short stature in subjects without GH deficiency and with a normal onset of
      puberty. We treated 10 girls with familial short stature with the GnRH analog
      leuprolide (3.75 mg, im, every 25 days) and GH (0.1 IU/kg.day, sc, 6 days/week).
      The combined therapies were started simultaneously, and the patients were treated
      for 28.1 +/- 5.4 (range, 24-36) months. At the onset of treatment, chronological
      age was 11.6 +/- 1.4 yr, bone age was 10.6 +/- 0.9 yr, height was -2.7 +/- 0.7
      SD, predicted height (PH; Bayley-Pinneau score) was 143.2 +/- 3 cm. Target height
      was 147.6 +/- 5.6 cm. Tanner stage was II-III for breast and genitalia. During
      treatment, puberty was completely suppressed in all patients. Statistical
      analysis was performed using Student's t test for paired data. After 12 months of
      treatment, we observed a significant (P < 0.02) improvement of predicted height
      (146.2 +/- 3.4 cm). This improvement remained significant (147.6 +/- 3.5; P <
      0.001) when treatment was withdrawn. At that time, chronological age was 13.9 +/-
      1.2 yr, and bone age was 12.4 +/- 0.7 yr. At the present time (3 +/- 0.97 yr
      after discontinuation), all of the girls have reached a final height of 144.6 +/-
      3 cm (range, 140-149.3 cm). The final height is not significantly different
      compared with the PH at the beginning of treatment or with target height. These
      data show that in our patients, combined treatment with GnRH analog and GH,
      despite a significant improvement in PH during therapy and upon its withdrawal,
      does not result in a significant increase in adult stature. Larger and perhaps
      more prolonged studies in patients of both sexes are required to reach definitive
      conclusions. Nevertheless, the cost of this treatment in terms of both subject
      compliance and economic cost should be weighed against the small height gain, if
      any, that may be achieved.

PMID- 8530606
TI  - Sandostatin LAR in acromegalic patients: a dose-range study.
AB  - Sandostatin LAR is a sustained release formulation of octreotide that has been
      developed by microencapsulating the drug with biodegradable poly(lactide
      glycolide)-glucose. We have investigated the efficacy and tolerability of
      Sandostatin LAR given as a single dose im to patients with active acromegaly who
      showed good GH suppression during a 2- to 4-week pretreatment period with
      octreotide given sc. Two double blind studies were performed. Initially, 14
      patients were randomized and observed over 42 days after a single im injection of
      3, 6, 9, or 12 mg Sandostatin LAR. In the second study, 15 patients were
      randomized and observed over 60 days after a single im injection of either 20 or
      30 mg Sandostatin LAR. Assessments of 12-h GH and octreotide profiles and adverse
      events were made on day -14 (during treatment with Sandostatin, sc); day 0 (off
      treatment after wash-out period); days 1, 7, 14, 21, 28, 35, and 42; and, for
      study 2, also on days 49 and 60 after the im injection. Only injections of 20 or
      30 mg were followed by a suppression of basal GH and insulin-like growth factor I
      to levels comparable to those seen during sc treatment. The suppression of mean
      GH to less than 5 micrograms/L lasted for 4 weeks in the group receiving 20 mg
      and for at least 6 weeks in those given 30 mg Sandostatin LAR. The
      pharmacokinetic profile fitted a biphasic drug release model previously described
      for peptides in similar drug delivery systems. Serum concentrations correlated
      with the im administered dose. Suppression of GH and insulin-like growth factor I
      was achieved at serum octreotide concentrations exceeding approximately 600 ng/L.
      Tolerability was good. Sandostatin LAR holds promise as a valuable drug for the
      treatment of acromegaly. The results of ongoing long term studies will provide
      further necessary knowledge of the drug.

PMID- 8530607
TI  - Effect of glucocorticosteroid treatment on glucocorticoid receptor expression in
      human adipocytes.
AB  - The influence of glucocorticoid excess on expression of the glucocorticoid
      receptor (GR) and beta-adrenoceptor subtype was studied in isolated adipocytes
      obtained by sc fat biopsies from 17 healthy individuals. The biopsies were taken
      before and after 7 days of treatment with 25 mg prednisolone, given orally. GR
      and beta 1- and beta 2-adrenoceptor messenger ribonucleic acid (mRNA) levels were
      measured with a solution hybridization assay, and the number of beta 1- and beta
      2-adrenoceptor binding sites was determined in radioligand binding experiments.
      GR protein levels were determined by Western blot analysis using an anti-GR
      antibody. Both GR protein and GR mRNA levels decreased significantly (P < 0.05)
      by about 50% after treatment, whereas no significant changes were demonstrated in
      either beta 1- or beta 2-adrenoceptor mRNA levels. The number of beta 2
      adrenoceptor-binding sites, however, increased by 70% after treatment (P < 0.05),
      whereas the number of beta 1-adrenoceptor binding sites was not affected. The
      affinity of each receptor subtype was not significantly altered by steroid
      treatment. In conclusion, an in vivo glucocorticoid excess decreases GR mRNA as
      well as GR protein levels and selectively increases beta 2-adrenoceptor density
      in sc fat cells of healthy individuals. This indicates that glucocorticoids
      modulate human adipose metabolism by altering the expression of regulatory
      proteins at various mRNA and post-mRNA levels.

PMID- 8530608
TI  - Three novel mutations of thyroid hormone receptor beta gene in unrelated patients
      with resistance to thyroid hormone: two mutations of the same codon (H435L and
      H435Q) produce separate subtypes of resistance.
AB  - We report three novel mutations of the thyroid hormone receptor beta (TR beta)
      gene in three unrelated Japanese patients with resistance to thyroid hormone
      (RTH). Patients A and B exhibited generalized resistance phenotype, while patient
      C displayed more pituitary-selective unresponsiveness. Direct sequencing of TR
      beta gene exon 10 disclosed novel point mutations in all three patients. A Phe to
      Ile (TTC-->ATC) substitution at codon 451, a His to Leu (CAT-->CTT) substitution
      at codon 435, and a His to Gln (CAT-->CAA) substitution at codon 435 were
      identified in patients A, B, and C, respectively. Sequencing of TR beta gene
      exons 5-9 as well as TR alpha gene exons 4-9 failed to detect any additional
      mutations. All three patients were heterozygous for respective mutations. The
      unaffected parents of patients A and B, having normal thyroid function, possessed
      no mutations of TR beta gene exon 10, indicating that the F451I and H435L
      mutations occurred de novo. The F451I mutation is located near the most frequent
      mutation site in the ligand 2 subdomain. The identical codon mutations H435L and
      H435Q, which lie at the extreme carboxyl-terminus of the dimerization subdomain
      near the 9th heptad, were found in clinically different subtypes of RTH: patient
      B with generalized resistance and patient C with pituitary-selective resistance,
      respectively. The mutations broaden the growing catalogue of the TR beta gene
      mutations that could cause different phenotypes, despite the defects at the same
      codon.

PMID- 8530609
TI  - 11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining
      the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.
AB  - A characteristic feature of the ectopic ACTH syndrome is a state of
      mineralocorticoid excess, although the etiology remains obscure. Some forms of
      endocrine hypertension, such as licorice ingestion, have been explained by
      cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency
      of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible
      for the conversion of cortisol (F) to hormonally inactive cortisone, and its
      activity in vivo can be inferred from the ratio of the urinary excretion of
      tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone.
      Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic,
      and 2 adrenal adenomas) and 13 controls were studied. Compared to controls.
      Cushing's patients had a significant increase (P < 0.001) in the excretion of all
      principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol
      secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1
      (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha
      THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome
      regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81
      (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD
      activity. Furthermore, compared to patients with pituitary-dependent Cushing's,
      this ratio was significantly higher in patients with the ectopic ACTH syndrome
      (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium
      levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid
      excess state of the ectopic ACTH syndrome appears to be that cortisol gains
      inappropriate access to the mineralocorticoid receptor through failure of its
      normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD
      activity is unclear, but it may be secondary to substrate saturation, inhibition
      by other adrenal steroids, or product inhibition.

PMID- 8530610
TI  - Cell-specific expression of estrogen receptor in the human pituitary and its
      adenomas.
AB  - Estrogen affects the synthesis and release of several pituitary hormones. The
      estrogen receptor (ER), a member of the steroid hormone receptor family, is
      thought to mediate transcriptional effects in a cell-specific fashion. We
      investigated whether ER is expressed in specific hormone-producing cell types in
      the human pituitary and its adenomas. Pituitary adenomas (n = 34) were collected
      at the time of surgery, and normal glands were obtained from autopsy. Expression
      of ER messenger ribonucleic acid (mRNA) was determined by reverse transcription
      polymerase chain reaction (RT-PCR) and in situ hybridization. ER was also
      localized with immunohistochemistry and protein extraction. By RT-PCR, ER mRNA
      was found in the nontumorous pituitary and in pituitary adenomas expressing only
      PRL, in those producing GH and PRL, and in adenomas expressing the gonadotropic
      hormones. No ER mRNA was detected in adenomas expressing only GH without PRL or
      gonadotropins, nor in tumors producing ACTH without PRL or gonadotropins. In situ
      hybridization was not as sensitive or specific as RT-PCR. Biochemical analysis
      performed on seven tumors that were positive for ER mRNA by RT-PCR detected ER
      protein in only one PRL adenoma and one oncocytoma and yielded negative or
      equivocal results in one PRL adenoma, three GH-PRL adenomas, and one null cell
      adenoma. ER protein was localized by immunohistochemistry in scattered cells of
      the nontumorous adenohypophysis and in a few PRL and gonadotroph adenomas. We
      conclude that ER expression, as determined by RT-PCR, correlates with the
      expression of PRL or gonadotropins; in contrast, ER mRNA was not detected in
      adenomas that express only GH or ACTH. These findings implicate ER as a cell
      specific transcription factor that may regulate cytodifferentiation in the
      pituitary.

PMID- 8530611
TI  - Decreased bone formation and increased mineral dissolution during acute fasting
      in young women.
AB  - Severe chronic undernutrition is associated with decreased bone turnover and
      significant bone loss. However, little is known about the short-term effects of
      nutritional deprivation on bone turnover. To investigate the effects of short
      term fasting on bone metabolism and the contribution of acidosis to these
      changes, 14 healthy women ages 18-26 (mean, 21 +/- 2 (SD years) were randomized
      to potassium bicarbonate (KHCO3, 2 meq/kg/day in divided doses) to prevent
      acidosis or control (potassium chloride, 25 meq/day) during a complete 4-day
      fast. Bone turnover was assessed using specific markers of formation [osteocalcin
      (OC) and Type I procollagen carboxyl-terminal propeptide (PICP)] and resorption
      [pyridinoline (PYRX) and deoxypyridinoline (DPYRX)]. Serum bicarbonate levels
      fell significantly from 27.0 +/- 3.2 to 17.3 +/- 2.6 mmol/L (P < 0.01) in the
      control group and were decreased compared to patients receiving KHCO3 [17.3 +/-
      2.6 vs. 23.4 +/- 2.4 mmol/L, (P < 0.001)]. Serum total and ionized calcium
      increased significantly in the control group [9.1 +/- 0.1 to 9.4 +/- 0.2 mg/dL (P
      < 0.01) and 1.20 +/- 0.03 to 1.23 +/- 0.03 mmol/L (P < 0.05), respectively], but
      not in patients receiving KHCO3. In addition, serum parathyroid hormone (PTH)
      levels decreased from 32 +/- 17 to 16 +/- 10 pg/mL (P < 0.05) and urinary calcium
      excretion increased [86 +/- 51 to 182 +/- 103 mg/day (P = 0.01)] in the control
      group, but not in patients receiving KHCO3. Serum osteocalcin (OC) and
      procollagen carboxyl-terminal propeptide (PICP) levels decreased significantly
      after 4 days of fasting from 9.1 +/- 3.4 to 5.5 +/- 4.2 ng/mL (P < 0.01) and 121
      +/- 21 to 46 +/- 13 ng/mL (P = 0.0001) respectively in the patients receiving
      bicarbonate, and from 10.1 +/- 3.3 to 4.0 +/- 2.9 ng/mL (P < 0.01) and from 133
      +/- 22 to 47 +/- 19 ng/mL (P < 0.001) respectively in the control group. The
      decrease in osteocalcin and PICP during fasting was comparable in both treatment
      groups. By contrast, urinary excretion of PYRX and DPYRX did not change
      significantly in either group with 4 days of fasting. These data are the first to
      demonstrate that markers of bone formation decline significantly with short-term
      fasting, independent of changes in acid-base status. By contrast, these data
      demonstrate a direct effect of acidosis in stimulating calcium release from bone
      during short-term fasting and suggest that acidosis may increase mineral
      dissolution independent of osteoclast activation and PTH in this experimental
      model of acute starvation.

PMID- 8530612
TI  - Sequential changes in serum thyroid peroxidase following radioiodine therapy of
      patients with differentiated thyroid carcinoma.
AB  - To determine the detectability and the time course of serum thyroid peroxidase
      (TPO) levels before and 1, 2, 4, and 6 months after 131I administration, we
      evaluated TPO in 13 selected patients with differentiated thyroid carcinoma (DTC)
      whose sera did not contain antimicrosomal or antithyroglobulin (Tg) antibodies.
      All patients received 131I therapy 6 or 8 weeks after thyroid surgery for
      ablation of the postsurgical thyroid remnant. Serum samples were also collected
      from 10 normal subjects. Measurement of TPO was carried out by using a new
      commercially available immunoluminometric assay with a sensitivity of 30 pg/mL.
      Serum Tg was measured by RIA with a sensitivity of 2.6 micrograms/L before and 6
      months after 131I administration. In all patients, a standard total body scan was
      obtained before and 6 months after 131I administration. TPO was undetectable in
      all sera from normal subjects. However, serum TPO became detectable in all
      patients with DTC during the study, whereas rescans were either negative or
      positive and appeared not to be related to the radioiodine dose given, histology
      of the thyroid tumor, residual thyroid volume, TSH levels, or age of patients.
      However, a significant negative correlation was present between TPO levels before
      131I administration and the time from surgery (r = -0.82, P < 0.001). Six of 13
      patients had increased TPO levels 1 month after 131I administration. Serum TPO
      levels tended to decrease during follow-up in most patients (7 of 10) with a
      negative rescan. In 3 patients with positive rescans, TPO levels tended to
      increase during follow-up. Patients with negative rescans had values of serum TPO
      overlapping the range of values seen in patients with positive rescans, thus
      demonstrating the inability of TPO assay as a useful marker for following
      patients with DTC. We found no correlation between Tg and TPO levels measured
      before and 6 months after 131I administration, thereby excluding TPO levels as a
      marker for thyroid cancer. Our results suggest that TPO, unlike Tg, does not
      appear to be a useful marker for following patients with DTC.

PMID- 8530613
TI  - Hypoestrogenemia and rhabdomyelysis (myoglobinuria) in the female judoist: a new
      worrying phenomenon?
AB  - It is now well established that strenuous engagement in aerobic endurance sports
      may cause menstrual problems and hypoestrogenemia-related phenomena, such as
      osteoporosis. The present study was designed to assess whether the competitive
      practice of female judoists produces specific physiological changes in
      menstruation and bone and muscle metabolism. A test group of 17 white female
      judoists (mean VO2max, 50.9 +/- 2.8 mL/kg.min; mean percent body fat, 16.3 +/-
      3.3%), a reference group of oarswomen, and a group of sedentary women
      participated in this study. Specific metabolic parameters were determined before
      and after a heavy 5-week pre-Olympic training period. With regard to
      anthropometrical characteristics, after a period of intensive training, female
      judoists significantly differed (P < 0.05) from their pretraining values for
      percent body fat (-2.2%) and number of oligomenorrheic individuals (+28.4%). Mean
      baseline posttraining luteal phase plasma levels of estrone (78 +/- 26 pmol/L),
      estradiol (85 +/- 70 pmol/L), LH (7.6 +/- 2.8 IU/L), and progesterone (13.4 +/-
      3.1 nmol/L) were significantly lower than those in both reference groups,
      although pretraining values did not significantly differ from those in a group of
      oarswomen. Luteal phase posttraining urinary parameters of muscular catabolism (3
      methylhistidine, 367 +/- 30 mmol/day) and collagen turnover (hydroxyproline, 678
      +/- 14 mumol/L) were significantly higher than those in a group of oarswomen (3-
      methylhistidine, 183 +/- 18 mmol/day; hydroxyproline, 196 +/- 21 micrograms/mL).
      Total plasma spontaneous monocyte interleukin-1 activity, an experimental
      parameter for bone turnover and formation, was significantly higher (P < 0.05) in
      both female judoists (15.8 +/- 3.0% max) and oarswomen (7.1 +/- 1.8% max) than in
      sedentary women (5.2 +/- 2.2% max). These findings were accompanied by a
      subjective feeling of musculotendinous soreness and fatigue. Posttraining values
      for blood diagnostic enzymes, such as creatinine phosphokinase, glutamic
      oxalacetic transaminase, lactic dehydrogenase, and uric acid exceeded 2-5 times
      maximal normal laboratory reference values. We believe that these overtraining
      like findings should be further examined to study the eventual causal
      relationship between hypoestrogenemia and rhabdomyelysis (myoglobinuria) and to
      fully understand the extent of these results and their importance to the female
      athlete's health.

PMID- 8530614
TI  - Insulin-like growth factor-binding protein-2 and insulin: studies in children
      with type 1 diabetes mellitus and maturity-onset diabetes of the young.
AB  - The regulation of circulating insulin-like growth factor-binding protein-2 (IGFBP
      2) in humans is not well understood. In vitro and animal data have identified the
      role of insulin in the regulation of IGFBP-2, but such a relationship has not
      been established clearly in humans. In the present study, serum IGFBP-2
      concentrations were assessed by Western ligand blot and immunoblot analysis in
      children with newly diagnosed and untreated insulin-dependent diabetes mellitus
      (IDDM) and maturity-onset diabetes of the young before and at various times after
      insulin therapy. For comparison, IGFBP-2 levels were also determined in lean and
      obese age-matched controls. Children with IDDM were grouped according to their
      serum bicarbonate levels at the time of presentation (group A, > 20; group B, 13
      20; group C, < 13 milliequivalents/L). Densitometric analysis demonstrated that
      before insulin therapy, group A patients had serum IGFBP-2 levels comparable to
      those in lean controls, and no significant change in IGFBP-2 was observed during
      insulin therapy. However, group B patients had a 2-fold elevation in IGFBP-2
      levels before insulin therapy compared to lean controls. In these patients, IGFBP
      2 tended to decrease at 1 week, but was not significantly reduced until 1 month
      after the initiation of insulin therapy. Group C patients had a 2.5-fold
      elevation of IGFBP-2 before treatment, which normalized by 1 month after
      treatment. Children with maturity-onset diabetes of the young, who had insulin
      levels and body mass indexes greater than IDDM patients and lean controls, had
      significantly lower IGFBP-2 levels than both lean and obese controls. IGFBP-2
      levels tended to decrease further during insulin therapy. These results indicate
      that long standing alterations in serum insulin concentrations beyond the
      physiological range have significant influence on serum IGFBP-2 levels in
      children and confirm earlier findings that serum IGFBP-2 levels are not acutely
      regulated by insulin.

PMID- 8530615
TI  - Clinical characteristics of subacute thyroiditis classified according to human
      leukocyte antigen typing.
AB  - We investigated human leukocyte antigen (HLA) class I and class II antigens in 56
      Japanese patients with subacute thyroiditis (SAT) who visited our out-patient
      clinic between 1988 and 1990. We found SAT to be associated with not only HLA-B35
      (40 patients; P < 0.000001; relative risk, 18.02), but also with HLA-B67 antigens
      (9 patients; P < 0.00001; relative risk, 11.20). No heterozygotes of HLA-B35 or
      HLA-B67 were found in any of the 56 patients with SAT. Either HLA-B35 or HLA-B67
      antigen is found in 87% of patients with SAT. When season of onset and clinical
      course of SAT were compared in the 49 patients with HLA-B35-positive SAT (B35
      SAT) and HLA-B67-positive SAT (B67-SAT), we were able to identify certain
      characteristics: 1) B67-SAT often followed the course from transient
      thyrotoxicosis to a hypothyroid phase to a euthyroid phase [6 of 9 B67-SAT (67%)
      vs. 10 of 40 B35-SAT (25%); P < 0.05]; and 2) B67-SAT occurred mostly during the
      summer or autumn and at a higher rate than did B35-SAR [8 of 9 B67-SAT (89%) vs.
      17 of 40 B35-SAT (43%)], whereas B35-SAT occurred throughout the year. We
      conclude that there are at least two types of SAT that can be classified by
      association with either HLA-B35 or HLA-B67 antigens.

PMID- 8530616
TI  - Calcium absorption on high and low calcium intakes in relation to vitamin D
      receptor genotype.
AB  - The finding that the link between polymorphism at the vitamin D receptor (VDR)
      gene and rates of bone loss from the femoral neck in postmenopausal women is
      enhanced at low calcium intakes suggests that intestinal calcium absorption is a
      site of differential action of the VDR alleles. 1,25-Dihydroxyvitamin D [1,25
      (OH)2D] and its receptor mediate active calcium transport, the major mechanism of
      calcium absorption at low calcium intakes. We compared fractional calcium
      absorption in healthy late postmenopausal women with (bb) and without (BB) the
      BSM-1 restriction site. In 60 women (26 BB and 34 bb), we measured calcium
      absorption and plasma 1,25-(OH)2D after 2 weeks on a high (1500 mg/day) and 2
      weeks on a low (< 300 mg/day) calcium intake. The mean 45Ca absorption indexes
      were similar in the two groups on the high calcium intake [19.01 +/- 1.12% (+/-
      SEM)/L in BB and 20.45 +/- 0.97%/L in bb; P = 0.346] and differed significantly
      on the low calcium intake (20.57 +/- 1.10%/L vs. 23.66 +/- 0.95%/L; P = 0.044).
      Calcium restriction induced similar percent increases in plasma 1,25-(OH)2D, but
      the BB group had a smaller increase in the fractional 45Ca absorption index [7.8
      +/- 3.8% (+/- SEM) vs. 20.7 +/- 3.3% in bb; P = 0.016; increments adjusted for
      initial absorption value]. In conclusion, compared to women with the bb variants,
      women with BB allelic variants of the VDR have reduced calcium absorption
      efficiency on low calcium intake, consistent with a functional defect in the
      intestinal VDR. The impact of this heritable difference is reduced at higher
      calcium intakes.

PMID- 8530617
TI  - Insulin resistance associated with substitution of histidine for arginine 252 in
      the alpha-subunit of the human insulin receptor: trial of insulin-like growth
      factor I injection therapy to enhance insulin sensitivity.
AB  - Mutation of the insulin receptor gene can compromise the ability of the receptor
      to mediate insulin action. A homozygous point mutation that results in the
      substitution of histidine for arginine 252 in the insulin receptor alpha-subunit
      has now been identified by polymerase chain reaction and single stranded
      conformational polymorphism analysis in a 20-yr-old Japanese woman with type A
      syndrome and severe insulin resistance. The proband's consanguineous parents
      (diabetic mother and normal father) and her sister (impaired glucose tolerance),
      each of whom showed an exaggerated insulin response to an oral glucose load, were
      heterozygous for this mutation. Her brother showed a normal insulin response and
      lacked the mutation, as did 50 healthy Japanese control subjects. The chronic sc
      administration of insulin-like growth factor I (IGF-I) improved the patient's
      hyperglycemia and corrected certain metabolic abnormalities over a 9-month
      period, even though the binding of 125I-labeled IGF-I to her cultured fibroblasts
      was decreased by 40% relative to that to cells from healthy controls. Studies of
      the binding of 125I-labeled insulin to the proband's cultured fibroblasts, to COS
      I cells transfected with complementary DNA encoding the mutant insulin receptor,
      and to partially purified mutant receptors revealed that the Arg252-->His
      mutation decreased both cell surface expression and the affinity for insulin for
      the receptor. These observations suggest that the homozygous Arg252-->His
      mutation is responsible for the type A insulin resistance of the proband, whereas
      in the heterozygous state, the mutation results in mild insulin resistance
      indistinguishable from that observed in noninsulin-dependent diabetes mellitus.

PMID- 8530618
TI  - Characterization of a low molecular mass form of insulin-like growth factor
      binding protein-3 (17.7 kilodaltons) in urine and serum from healthy children and
      growth hormone (GH)-deficient patients: relationship with GH therapy.
AB  - The insulin-like growth factor binding proteins (IGFBPs) are the carriers for
      insulin-like growth factor (IGF0-I and IGF-II. IGFBP-3 is GH-dependent and
      circulates associated with IGFs and an acid-labile subunit to form a 150
      kilodalton (kDa) complex. In human serum, two immunoreactive molecular weight
      forms of IGFBP-3 have been identified. In human urine, radioimmunoassayable
      levels of IGFBP-3 have been detected. The objectives of this study were to
      characterize the molecular weight forms of IGFBP-3 in urine and serum of healthy
      children and adults and in children with GH deficiency (GHD), to quantify the
      urinary molecular weight forms of IGFBP-3, and to evaluate the relationship of
      these forms with GH therapy. Urine and serum were obtained from 12 prepubertal
      children with GHD, before and after 6 months of GH therapy, from 30 prepubertal
      healthy children, and from 8 healthy adults. Western immunoblotting (WIB) with
      IGFBP-3 antiserum (alpha IG-FBP-3g1) showed that in urine the most representative
      IGFBP-3 was a 17.7-kDa form. The 17.7-kDa IGFBP-3 was high in urine of healthy
      children compared with healthy adults and was low in children with GHD but
      increased after GH therapy. Urinary IGFBP-3 immunoreactive profile was determined
      by neutral-size exclusion chromatography, followed by IGFBP-3 RIA analysis of the
      fractions. Urine showed a major peak of IGFBP-3 immunoreactivity around 17 kDa.
      The 17-kDa urinary IGFBP-3 chromatographic peak averaged 8461 +/- 367 ng/12 h.m2
      of body surface in healthy children, 3415 +/- 739 in adults (P < 0.001), 2294 +/-
      354 in children with GHD before GH therapy (P < 0.001), and 7940 +/- 1874 in
      children with GHD after GH therapy. Urinary IGFBP-3 was also measured by RIA in
      unfractionated urine; healthy children showed levels significantly higher (14575
      +/- 460 ng/12 h.m2) than adults (7823 +/- 1083, P < 0.001) and higher than
      children with GHD before GH therapy (4710 +/- 703, P < 0.001). Again, however,
      immunoreactive IGFBP-3 increased after GH treatment (12294 +/- 3394). In the
      serum of the healthy children we characterized by specific IGFBP-3 WIB analysis,
      a 17.7-kDa immunoreactive form of IGFBP-3 that was absent in the serum of healthy
      adults and low in patients with GHD, increased during GH therapy. Serum samples
      were subjected to neutral-size exclusion chromatography and the fractions were
      analyzed by WIB.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8530619
TI  - Lack of association between vitamin D receptor genotypes and osteoporosis in
      Koreans.
AB  - To evaluate whether common allelic variants in the gene encoding the vitamin D
      receptor (VDR) were useful in predicting differences in bone mineral density
      (BMD) and bone turnover rate in Koreans, we analyzed the restriction pattern of
      the polymerase chain reaction product of the VDR gene with the Bsm1 enzyme and
      serum osteocalcin in patients with osteoporosis. The prevalence of the BB
      genotype in the controls was extremely low when compared with that in other
      reports: the BB, Bb, and bb genotypes accounted for 1.4%, 12.9%, and 85.7%,
      respectively. Only 2.8% of those patients with osteoporosis had the BB genotype.
      In contrast, 12.5% had the Bb genotype, and 84.7% had the bb genotype. The
      prevalence of the BB genotype in patients with severe osteoporosis was also
      extremely low: the BB, Bb, and bb genotypes accounted for 0%, 12.4%, and 87.6%,
      respectively. Compared with the mean serum osteocalcin level of the pre- and post
      menopausal controls, the level in patients with severe osteoporosis was higher,
      and this was statistically significant. As expected, a negative correlation was
      observed between the serum osteocalcin levels and the age-matched Z scores for
      spinal BMD. However, no correlation was found in the femoral neck BMD. These
      results suggest that restriction fragment length polymorphism analysis of the VDR
      gene with a Bsm1 restriction enzyme in Koreans is not helpful for early detection
      of patients at risk of developing osteoporosis. This is true even in patients
      with a high rate of bone turnover. Our data suggest extreme ethnic differences in
      the pattern of prevalence of the VDR allele.

PMID- 8530620
TI  - Defective regulation of glycoprotein free alpha-subunit in males with isolated
      gonadotropin-releasing hormone deficiency--a clinical research center study.
AB  - During long term replacement with a GnRH regimen that restores their gonadotropin
      and sex steroid levels to normal, men with idiopathic hypogonadotropic
      hypogonadism (IHH) exhibit excessive secretion of pituitary free alpha-subunit
      (FAS). To characterize further the dose and duration of exogenous GnRH required
      to elicit this response, FAS, LH, FSH, and testosterone were determined during
      the first 8 weeks of GnRH administration in 10 men with IHH. The GnRH dose was
      increased stepwise every 2 weeks from 5 to 100 ng/kg every 2 h. Hormonal
      responses were compared with normative data for both pubertal boys and adult men.
      Low baseline levels of LH (mean +/- SEM, 0.9 +/- 0.03 IU/L), FSH (2.5 +/- 0.4
      IU/L), FAS (148 +/- 21 ng/L), and testosterone (2.5 +/- 0.3 nmol/L) increased
      progressively after GnRH replacement. Mean FAS levels and pulse amplitudes
      significantly exceeded those in normal adult men by 4-6 weeks when their LH
      responses to GnRH administration remained below adult norms. By week 8 (50 ng
      GnRH/kg every 2 h), mean levels of LH, FSH, and FAS (13.7 +/- 2.1 IU/L, 15.4 +/-
      4.0 IU/L, 627 +/- 75 ng/L, respectively) significantly exceeded adult male
      concentrations (P < 0.03). However, mean LH and FSH concentrations were not
      significantly different from midpubertal controls, in whom FAS levels were
      comparable to those in normal adults, verifying the excessive nature of FAS
      secretion relative to intact gonadotropins in the IHH patients. As this imbalance
      between FAS and dimeric gonadotropin secretion was established early in the
      current study when low doses of GnRH presumably resulted in low levels of
      receptor occupancy in vivo, it does not appear to result from partial pituitary
      desensitization induced by pharmacological GnRH stimulation. Rather, it appears
      to represent an inherent property of the GnRH-deficient state that is unmasked
      when GnRH input to the pituitary is restored. Further work will be necessary to
      elucidate the mechanism of this apparent defect in FAS regulation in GnRH
      deficient men.

PMID- 8530621
TI  - Aromatase deficiency in male and female siblings caused by a novel mutation and
      the physiological role of estrogens.
AB  - The aromatase enzyme complex catalyzes the conversion of androgens to estrogens
      in a wide variety of tissues, including the ovary, testis, placenta, brain, and
      adipose tissue. Only a single human gene encoding aromatase P450 (CYP19) has been
      isolated; tissue-specific regulation is controlled in part by alternative
      promoters in a tissue-specific manner. We report a novel mutation in the CYP19
      gene in a sister and brother. The 28-yr-old XX proband, followed since infancy,
      exhibited the cardinal features of the aromatase deficiency syndrome as recently
      defined. She had nonadrenal female pseudohermaphrodism at birth and underwent
      repair of the external genitalia, including a clitorectomy. At the age of
      puberty, she developed progressive signs of virilization, pubertal failure with
      no signs of estrogen action, hypergonadotropic hypogonadism, polycystic ovaries
      on pelvic sonography, and tall stature. The basal concentrations of plasma
      testosterone, androstenedione, and 17-hydroxyprogesterone were elevated, whereas
      plasma estradiol was low. Cyst fluid from the polycystic ovaries had a strikingly
      abnormal ratio of androstenedione and testosterone to estradiol and estrone.
      Hormone replacement therapy led to breast development, menses, resolution of
      ovarian cysts, and suppression of the elevated FSH and LH values. Her adult
      height is 177.6 cm (+2.5 SD). Her only sibling, an XY male, was studied at 24 yr
      of age. During both pregnancies, the mother exhibited signs of progressive
      virilization that regressed postpartum. The height of the brother was 204 cm
      (+3.7 SD) with eunuchoid skeletal proportions, and the weight was 135.1 kg (+2.1
      SD). He was sexually fully mature and had macroorchidism. The plasma
      concentrations of testosterone (2015 ng/dL), 5 alpha-dihydrotestosterone (125
      ng/dL), and androstenedione (335 ng/dL) were elevated; estradiol and estrone
      levels were less than 7 pg/mL. Plasma FSH and LH concentrations were more than 3
      times the mean value. Plasma PRL was low; serum insulin-like growth factor I and
      GH-binding protein were normal. The bone age was 14 yr at a chronological age of
      24 3/12 yr. Striking osteopenia was noted at the wrist. Bone mineral
      densitometric indexes of the lumbar spine (cancellous bone) and distal radius
      (cortical bone) were consistent with osteoporosis; the distal radius was -4.7 SD
      below the mean value for age- and sex-matched normal men; indexes of bone
      turnover were increased. Hyperinsulinemia, increased serum total and low density
      lipoprotein cholesterol, and triglycerides and decreased high density lipoprotein
      cholesterol were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8530622
TI  - Elevated parathyroid hormone-related peptide levels after human gestation:
      relationship to changes in bone and mineral metabolism.
AB  - PTH-related peptide (PTHrP) can be found in high concentrations in human breast
      milk and has been implicated in material calcium regulation postpartum. We
      studied the relationship of plasma PTHrP levels of serum markers of bone turnover
      and selective cancellous bone density in 35 women (age, 25 +/- 3 yr) 2-3 days
      postpartum and after 3 and 6 months of lactation. The mean postpartum plasma
      PTHrP levels measured by immunoradiometric assay was 2.64 +/- 0.19 pmol/L (mean
      +/- SE) and were elevated compared to that in 35 age- and sex-matched controls
      (1.34 +/- 0.14; P < 0.0001). PTHrP remained significantly elevated, but decreased
      during the lactation period of 6 +/- 1 months. Immediately postpartum, serum
      protein levels were lowest, and serum ionized calcium levels highest. At that
      time, PTH was suppressed to 50% of control values (P < 0.001). Two or 3 days
      postpartum, serum ionized calcium was negatively correlated with total serum
      protein (r = -0.47; P < 0.0001) and positively correlated with plasma PTHrP (r = 
      0.32; P < 0.008). PTH was inversely correlated with ionized calcium (r = -0.24; P
      = 0.03) and PTHrP (r = -0.31; P < 0.01). Three and 6 months postpartum, serum
      protein and PTH levels had returned to normal, and ionized calcium concentrations
      decreased. There was no indication that PTHrP may have any significant systemic
      effect after 3 and 6 months of lactation. Long term lactation led to a
      significant decrease in radial cancellous bone density (-4.5%; P < 0.05) at 6
      months and to elevations in serum markers of bone resorption (2- to 3-fold for
      serum carboxy-terminal telopeptide of type I collagen) and formation (1- to 2
      fold for osteocalcin and serum carboxy-terminal propeptide of type I
      procollagen). Bone turnover balance was clearly negative after 3 months of
      lactation compared to the control value and indicated net bone loss at a time
      when estrogen levels were low. With ongoing lactation, estrogen levels increased,
      and bone turnover balance improved significantly and independently of PTHrP
      levels. We interpret these results as evidence that PTHrP is elevated during the
      postgestational period and has a weak and temporary effect on calcium metabolism
      when serum protein levels are reduced. PTHrP does not seem to participate
      significantly in the regulation of bone turnover during lactation. Normalization
      of bone turnover balance at 6 months of lactation suggests that further
      cancellous bone loss is most likely minimal when breast-feeding is extended
      beyond that time.

PMID- 8530623
TI  - The role of endothelin-1 in regulating human granulosa cell proliferation and
      steroidogenesis in vitro.
AB  - The effects of endothelin-1 (ET-1) on luteinized human granulosa cells (L-HGCs)
      have not been examined. It is well known that there are differences of actions of
      several autocrine/paracrine regulators between L-HGCs and GCs of other species,
      and therefore the present study was designed to examine the effects of ET-1 1) on
      intracellular Ca2+ concentrations ([Ca2+]i) using the Ca(2+)-responsive
      fluorescent indicator Fura-2, 2) on cell proliferation by the nonradioactive
      method using bromodeoxyuridine, and 3) on basal and gonadotropin-stimulated
      steroidogenesis, and to examine the expression of ET receptor messenger RNA
      (mRNA) using freshly isolated and cultured L-HGCs obtained from patients
      undergoing in vitro fertilization. ET-1 increased [Ca2+]i in L-HGCs in a dose
      dependent manner between 1 and 1000 nmol/L. High concentrations (100-1000 nmol/L)
      of ET-1 produced a more rapid and transient increase in [Ca2+]i than that
      observed with low concentrations (1-10 nmol/L) of ET-1. The increase in [Ca2+]i
      elicited by ET-3 (1000 nmol/L) and IRL-1620 (1000 nmol/L), a selective ETB
      receptor agonist, was 16% and 3% (vs. ET-1, 100%), respectively. BQ-123 (1000
      nmol/L), an ETA receptor antagonist, inhibited the increase in [Ca2+]i elicited
      by ET-1 (by 50% at 1000 nmol/L ET-1 and by > 90% at < 500 nmol/L ET-1). mRNAs for
      the two known receptor subtypes (ETA and ETB) were also present in L-HGCs;
      however, the expression of ETA receptor mRNA was much greater than that of ETB
      receptors. ET-1 stimulated cell proliferation in L-HGCs in a dose-dependent
      manner (1000 nmol/L, 210.5 +/- 13.1%; 100 nmol/L, 198 +/- 11%; 10 nmol/L, 146 +/-
      18%; and 1 nmol/L, 103 +/- 9%; vs. control, 100%). These stimulatory effects were
      completely blocked by BQ-123 (1000 nmol/L). ET-3 and IRL-1620 had no effects on
      cell proliferation in L-HGCs. Significant stimulatory effects on cell
      proliferation by the calcium ionophore, ionomycin (10-1000 nmol/L), were
      observed. ET-1, ET-3, and IRL-1620 attenuated basal progesterone secretion in L
      HGCs. These results suggest that ETA receptor predominantly exist in L-HGCs and
      that ET-1 may stimulate cell proliferation of L-HGCs by increasing [Ca2+]i via
      ETA receptors.

PMID- 8530624
TI  - Metabolic and clinical response to recombinant human insulin-like growth factor I
      in myotonic dystrophy--a clinical research center study.
AB  - Muscle weakness and wasting in myotonic dystrophy (MyD) are believed to be due to
      a decrease in muscle protein synthesis, secondary to insulin resistance. A 4
      month, randomized, double blind, placebo-controlled trial was undertaken to
      assess whether recombinant human insulin-like growth factor I (rhIGF-I) may
      overcome the insulin resistance. Patients received either 5 mg rhIGF-I (n = 7) or
      placebo (n = 9), sc, twice daily. Glucose metabolism was assessed by stable label
      iv glucose tolerance test, amino acid metabolism by L-[13C] leucine turnover,
      body composition by dual energy x-ray absorptiometry and N excretion, and muscle
      response by manual muscle strength and neuromuscular function. In the treated
      group, the insulin sensitivity index, insulin action, and glucose disposal all
      increased (P < 0.05). Leucine flux and leucine incorporation into protein
      increased (P < 0.05), and the rate of leucine oxidation to leucine turnover
      decreased (P < 0.05), findings indicative of increased protein synthesis. Body
      weight and lean body mass increased, whereas percent body fat decreased (P <
      0.05). An increase in manual muscle strength of 0.42 +/- 0.30 (P < 0.02) and in
      neuromuscular function of 17.5 +/- 11.7 (P < 0.02) occurred in the four patients
      who received a rhIGF-I dose greater than 70 micrograms/kg, whereas a more modest
      response occurred in the three patients who received a dose less than 70
      micrograms/kg. Two patients showed dramatic improvement. Long term rhIGF-I
      therapy appears to cause metabolic and muscle improvement in optimally treated
      MyD patients.

PMID- 8530625
TI  - Expression of intercellular adhesion molecule-1 on human thyroid cells from
      patients with autoimmune thyroid disease: study of thyroid xenografts in nude and
      severe combined immunodeficient mice and treatment with FK-506.
AB  - It has been suggested that intercellular adhesion molecule-1 (ICAM-1) may play an
      important role in the initiation, localization, and perpetuation of autoimmune
      thyroid diseases (AITD). In an effort to clarify its role, we have investigated
      the expression of ICAM-1 on thyroid epithelial cells (TEC) of patients with AITD,
      patients with nontoxic goiter (NTG), and normal subjects (PN) by flow cytometric
      analysis under basal conditions and after modulation with cytokines, before and
      after 8 weeks of thyroid tissue xenotransplantation in nude athymic mice (which
      lyses all passenger lymphocytes), and in severe combined immunodeficient (SCID)
      mice where these cells survive. Before xenografting, ICAM-1 was expressed on 56%
      of TEC from Hashimoto's thyroiditis (n = 5), 54% of Graves' disease (n = 6), 15%
      of NTG (n = 5), and 12% of PN TEC. After the xenografts had been 8 weeks in nude
      mice, ICAM-1 expression decreased markedly in AITD TEC [from 56% to 10% in
      Hashimoto's thyroiditis (P < 0.001) and from 54% to 8% in Graves' disease (P <
      0.01)], but did not change significantly in NTG or PN. After the xenografts had
      been 8 weeks in SCID mice, the expression of ICAM-1 was significantly higher on
      TEC of AITD compared with the same tissue in nude mice. When the SCID mice
      engrafted with AITD tissue were treated with the anti-CD4+ T (helper) cell agent
      FK-506, the expression of ICAM-1 was reduced significantly compared with that in
      the original tissue or that in nontreated mice engrafted with the same tissue.
      The proportion of TEC that were ICAM-1 positive was up-regulated in all cases by
      certain cytokines (e.g. interferon-gamma and tumor necrosis factor-alpha applied
      alone or in combination). We also detected the presence of ICAM-1 in AITD frozen
      tissues using an immunohistochemical technique. These data suggest a role for
      ICAM-1 in human AITD. However, the expression of ICAM-1 appears to be a secondary
      phenomenon in response to the immune assault, rather than a primary event. Our
      results support the idea that TEC may act as passive captives to immunological
      events in human AITD.

PMID- 8530626
TI  - Insulin-like growth factor I resistance in immortalized T cell lines from African
      Efe Pygmies.
AB  - Previous investigations suggested that resistance to GH was the cause of short
      stature of African Pygmies. Because many of the actions of GH are mediated by
      insulin-like growth factor I (IGF-I), we sought to determine whether Pygmy tissue
      was responsive to IGF-I. An initial effort to obtain HTLV-II-transformed T
      lymphoblast cell lines resulted in a single cell line that showed complete
      resistance to both IGF-I and GH in a clonal proliferation assay as well as
      decreased IGF-I binding. In the current study, we examined T cell lines from
      seven Efe Pygmy subjects, three neighboring Lese farmers, and six American
      controls and quantified clonal responses to IGF-I, GH, and insulin. The T cell
      lines from the Efe Pygmies were all completely resistant to the growth-promoting
      actions of IGF-I concentrations less than 250 micrograms/L and GH concentrations
      less than 500 micrograms/L. The Lese population, with whom there is admixture
      with the Efe population, showed heights and clonal responses to IGF-I and GH
      intermediate between those of Pygmies and American controls. The Pygmy T cell
      lines showed reduced clonal proliferation in response to high insulin
      concentrations known to act through the IGF-I receptor. These findings indicate
      that genetic IGF-I resistance is present in the T cell lines of Efe Pygmies and
      suggest that unresponsiveness to IGF-I may be responsible for their short
      stature.

PMID- 8530627
TI  - Age and family relationship accentuate the risk of insulin-dependent diabetes
      mellitus (IDDM) in relatives of patients with IDDM.
AB  - The international community of diabetologists is rapidly becoming involved in
      intervention trials aimed at preventing insulin-dependent diabetes in high risk
      relatives. Whereas age and relationship to a proband with insulin-dependent
      diabetes mellitus interacting with detected islet cell autoantibodies (ICA) are
      risk factors, their independent contribution to that risk remains unclear. In a
      prospective study of 6851 nondiabetic relatives of 2742 probands conducted
      between 1979-1993, we found age, but not relationship, to be a dramatic risk
      variable in ICA-positive persons as estimated by the Cox regression model. The 5
      yr risk of insulin-dependent diabetes mellitus was 66% for those found to have
      ICA detectable before age 10 yr, falling progressively to less than 16% for ICA
      positive relatives over age 40 yr. In ICA-negative relatives, age and
      relationship are independent prognostic variables.

PMID- 8530628
TI  - Thyroid function tests and characterization of thyroxine-binding globulin in the
      carbohydrate-deficient glycoprotein syndrome type I.
AB  - Carbohydrate-deficient glycoprotein (CDG) syndrome is a newly recognized
      hereditary disorder that presents with psychomotor retardation, cerebellar
      ataxia, peripheral sensorimotor neuropathy, and, variably, skeletal
      abnormalities, lipodystrophy, and retinitis pigmentosa. These abnormalities
      appear to be produced by a defect that causes reduced carbohydrate content in
      glycoproteins. We studied seven patients with CDG type I belonging to five
      unrelated families. The concentration of serum TBG, a glycoprotein of hepatic
      origin, was measured by RIA and T4 saturation and was found to be below the
      normal range in three of the seven patients and normal in four of them. More than
      half of the total serum TBG had reduced sialic acid content and localized on
      isoelectric focusing (IEF) as two prominent bands cathodal to the three major
      bands of normal TBG. The latter two bands are responsible for the characteristic
      IEF pattern or CDG syndrome. TBG in patients with CDG had immunoreactivity
      indistinguishable from that of normal TBG and had normal affinity for T4, T3, and
      rT3. Serum total T4, T3, and rT3 were below the normal range in seven, five, and
      seven patients, respectively. The free T4 index was also below normal in four
      patients, but the free T4 concentration, measured by equilibrium dialysis at low
      dilution, and serum TSH were in the midnormal range. The serum total T4 and rT3
      levels were disproportionately reduced relative to the serum TBG concentration
      and compared to the concentrations of these iodothyronines in matched subjects
      with inherited partial TBG deficiency. Chronic illness cannot explain these
      changes, because, contrary to patients with nonthyroidal illness, those with CDG
      had significantly higher serum total T3/T4 and lower rT3/T4 ratios. It is
      concluded that IEF of TBG is a rapid and simple method for the diagnosis of CDG
      type I and that the abnormal pattern can be detected as early as 5 days
      postpartum. Patients with CDG are chemically euthyroid, and it is postulated that
      the reduction in serum iodothyronine concentrations beyond that explained on the
      basis of low TBG levels may be due to the interference with binding to TBG by an
      unidentified substance.

PMID- 8530629
TI  - Combined amplification of the pulsatile and basal modes of adrenocorticotropin
      and cortisol secretion in patients with Cushing's disease: evidence for decreased
      responsiveness of the adrenal glands.
AB  - We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with
      Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min
      intervals, and data were analyzed with a multiparameter deconvolution technique.
      The patients had the same number of ACTH pulses per 24 h as the controls (34 vs.
      32/24 h) and similar plasma ACTH half-lives (17.4 +/- 0.7 vs. 19.3 +/- 0.5 min).
      The mass of ACTH secreted per pulse was increased, which was caused by an
      increased maximal secretion rate and prolonged secretion burst duration. The
      number of resolved cortisol pulses was less than that for ACTH, but higher in
      patients than in controls (24 vs. 17/24 h), with similar half-lives in both
      groups (57 +/- 2 vs. 59 +/- 4 min). The mass of cortisol secreted per pulse was
      higher in patients than in controls due to an increased maximal secretion rate
      attained within each burst. The mean total mass of 24-h cortisol production was
      12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients.
      Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7
      fold (cortisol) above control values in patients with Cushing's disease (P <
      0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per
      L distribution volume) was 23 +/- 1.9 in controls and 11 +/- 2.3 in patients (P <
      0.001). The secretory parameters for ACTH showed strong diurnal rhythms in
      control subjects, but were not significant in six patients. Diurnal rhythms for
      cortisol could be detected in only five patients. From these observations we
      conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile,
      with the preservation of diurnal properties in only some patients. Markedly
      amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7
      fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH
      and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the
      apparent response of the adrenal gland to increased ACTH levels is diminished,
      suggesting decreased responsiveness of the adrenal glands.

PMID- 8530630
TI  - Gene amplification as a cause of inherited thyroxine-binding globulin excess in
      two Japanese families.
AB  - T4-binding globulin (TBG) is the major thyroid hormone transport protein in man.
      Inherited abnormalities in the level of serum TBG have been classified as partial
      deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene,
      located on Xq21-22, has uncovered the molecular defects causing partial and
      complete deficiency. However, the mechanism leading to inherited TBG excess
      remains unknown. In this study, two Japanese families, F-A and F-T, with
      inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58
      and 44 micrograms/mL, 3- and 2-fold the normal value, respectively. The molecule
      had normal properties in terms of heat stability and isoelectric focussing
      pattern. The sequence of the coding region and the promoter activity of the TBG
      gene were also indistinguishable between hemizygotes and normal subjects. The
      gene dosage of TBG relative to that of beta-globin, which is located on
      chromosome 11, and Duchenne muscular dystrophy, which is located on Xp, was
      evaluated by coamplification of these target genes using polymerase chain
      reaction and subsequent quantitation by HPLC. The TBG/beta-globin ratios of the
      affected male and female of F-A were 3.13 and 4.13 times, respectively, that in
      the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09
      times the normal value, respectively. These results are compatible with three
      copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in
      gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem
      amplification of the TBG gene was shown by in situ hybridization of prometaphase
      and interphase chromosomes from the affected male with a biotinylated genomic TBG
      probe, confirming the gene dosage results. Gene amplification of TBG is the cause
      of inherited TBG excess in these two families.

PMID- 8530631
TI  - Aromatase expression in human germinomas with possible biological effects.
AB  - Gonadal aromatase expression has been demonstrated in human Leydig, granulosa,
      and thecal cells, but never in human germ cells. In an attempt to explain the
      unique occurrence of isosexual precocious puberty in a young girl with a hCG
      secreting suprasellar germinoma, we demonstrated the presence of aromatase
      expression in the germ cell component of this tumor. Immunohistochemical staining
      for P450-aromatase and hCG using a peroxidase-labeled streptaviden-biotin
      technique was performed on tumor specimens from the above patient and from four
      other subjects with central nervous system germinoma. Cytoplasmic aromatase
      staining was present in the germinoma cells of four of five cases of central
      nervous system germinoma studied. Staining was absent in the lymphocytic element
      within the tumor and in negative control tissues. The demonstration of aromatase
      activity in the malignant element of human germinomas indicates that aromatase
      expression can occur in human germ cells after malignant transformation. This
      parallels the finding that the transformation of Sertoli cells to sex cord tumor
      with annular tubules in Peutz Jeghers syndrome is associated with the induction
      of marked aromatase expression and systemic estrogen effect. We propose that
      tumor aromatase played a similar role in the unique occurrence of isosexual
      precocity in a girl with a suprasellar germinoma.

PMID- 8530632
TI  - Growth hormone pulsatility in active and cured acromegalic subjects.
AB  - GH secretion in normal subjects is periodic, with pulses prevailing during sleep.
      During the day (basal secretion), GH levels are, in general, undetectable. We
      studied GH secretion by cluster analysis, collecting samples every 20 min for 24
      h in 44 subjects: 11 patients with active acromegaly; 16 "cured" acromegalics,
      and 17 normal subjects. The purpose of this study was to compare GH secretion
      between patients with active acromegaly and "cured" patients and between "cured"
      acromegalic patients and normal controls. The number of pulses detected through
      the 24-h GH profile was not different between acromegalic patients regardless of
      disease activity (17.5 +/- 4.4 vs. 15.0 +/- 6.0, respectively), but was different
      when active acromegalic patients and normal controls were compared (8.1 +/- 1.0;
      P < 0.05) and when cured acromegalic patients and normal controls were compared
      (P < 0.05). The GH pulsatile secretion/total GH secretion ratio was higher in
      normal controls than in acromegalic patients regardless of disease activity. We
      concluded that 1) the increases in GH pulsatility in active and cured acromegalic
      patients are similar, but most of the 24-h GH secretion is nonpulsatile; 2) half
      of the GH secretion in normal subjects occurs during pulses; 3) cured acromegalic
      patients, even those with normal GH and insulin-like growth factor I levels, do
      not recover a normal GH secretory pattern.

PMID- 8530633
TI  - Absence of steroid biosynthetic defects in heterozygote individuals for classic
      11 beta-hydroxylase deficiency due to a R448H mutation in the CYP11B1 gene.
AB  - Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxy-cortisol to
      cortisol) is responsible for less than 5% of cases of classic congenital adrenal
      hyperplasia, but it is relatively frequent in Israel, among Jews of Moroccan
      origin. Affected individuals have a single base substitution in exon 8 of CYP11B1
      gene, codon 448, from CGC (arginine) to CAC (histidine) (R448H), a mutation that
      abolishes enzyme activity completely. We studied the hormonal response to ACTH
      stimulation in individuals genotyped to have the R448H mutation in one allele
      only (heterozygotes), and who were therefore assumed to have 50% of 11 beta
      hydroxylase activity. No demonstrable hormonal abnormalities were found in the 6
      adults (3 mothers and 3 fathers) and 2 sons studied, suggesting that a
      quantitatively reduced 11 beta-hydroxylase is still enough for normal adrenal
      biosynthesis.

PMID- 8530634
TI  - In obesity the somatotrope response to either growth hormone-releasing hormone or
      arginine is inhibited by somatostatin or pirenzepine but not by glucose.
AB  - It is known that spontaneous and stimulated GH secretion is reduced in obesity.
      On the other hand, it has been recently reported that, in obese subjects, plasma
      GH levels did not change during a hyperglycemic clamp. To further study the
      sensitivity of somatotrope cells to inhibitory influences in obesity, we studied
      the effect of somatostatin, pirenzepine, or glucose on the GH response to GHRH or
      arginine in 32 obese patients and 30 controls. Basal GH levels were lower in
      obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 micrograms/L, P <
      0.05), while insulin-like growth factor-I levels were similar in both groups
      (137.3 +/- 13.2 vs. 138.8 +/- 12.2 micrograms/L). In obese as well as in control
      subjects pirenzepine abolished the GH response to either GHRH (AUC0-120: 43.7 +/-
      9.6 vs. 258.3 +/- 59.9 micrograms/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/-
      255 micrograms/L.h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/
      55.9 micrograms/L.h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5
      micrograms/L.h, P < 0.01, respectively). Differently from pirenzepine, glucose
      blunted the GH response to either GHRH or arginine in control subjects (260.8 +/-
      38.3 vs. 479.5 +/- 83.9 micrograms/L.h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/-
      139.1 micrograms/L.h, P < 0.05, respectively), but failed to modify it in obese
      patients (193.7 +/- 39.4 vs. 172.4 +/- 33.6 micrograms/L.h and 121.1 +/- 43.4 vs.
      155.1 +/- 39.7 micrograms/L.h, respectively). On the other hand, somatostatin
      deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 vs.
      548.7 +/- 196.6 micrograms/L.h, P < 0.05) as well as in controls (181.4 +/- 44.4
      vs. 759.7 +/- 46.6 micrograms/L.h, P < 0.04). In conclusion, our results show
      that, in obesity, the stimulated GH release is refractory to the inhibitory
      effect of glucose but not of pirenzepine, in spite of their likely common
      mechanism of action, i.e. increase of hypothalamic somatostatin release.
      Exogenous somatostatin is able to abolish GH secretion both in normal and obese
      subjects. These data suggest the existence of a peculiar inhability of
      hyperglycemia to trigger somatostatinergic release in obesity.

PMID- 8530635
TI  - Constitution of a biphasic insulin response to glucose in human fetal pancreatic
      beta-cells with glucagon-like peptide 1.
AB  - Insulin release from fetal beta-cells responds only minimally to acute glucose
      stimulation. Glucagon-like peptide-1 (GLP-1) is able to correct glucose
      sensitivity in some models of glucose-resistant beta-cells. We have now tested
      whether GLP-1 can induce glucose-responsive insulin release in human fetal islet
      like cell clusters (ICCs). For this purpose we used perifusion and static
      incubation of ICCs and isolated adult human islets. In perifusion, the fetal ICCs
      responded with only minimal insulin release to 16.7 mmol/L glucose or 10 nmol/L
      GLP-1 combined with 1.67 mmol/L glucose. However, in the presence of GLP-1, the
      insulin response to glucose was markedly potentiated and appeared in a biphasic
      manner (10-fold first phase and 3-fold second phase). The first phase response
      was equal to that of adult human islets in similar experiments, whereas the
      second phase of the fetal cells was significantly lower. In static incubations,
      the relative insulin release responses to 16.7 mmol/L glucose plus 10 nmol/L GLP
      1 were equal in the fetal and adult cells. The cAMP content of the cells was
      increased by glucose only in the presence of GLP-1. Our studies indicate that the
      glucoincretin hormone GLP-1 is able to constitute biphasic insulin release in the
      immature beta-cell, possibly as the result of cAMP-mediated priming of the
      glucose sensor mechanism.

PMID- 8530636
TI  - Partial purification and amino acid sequence analysis of endometriosis protein-II
      (ENDO-II) reveals homology with tissue inhibitor of metalloproteinases-1 (TIMP
      1).
AB  - De novo synthesized endometriosis protein-II (ENDO-II; M(r) 28,000 to 32,000; pI
      7.0 to 9.0) was partially purified from rat endometriotic tissue culture media
      using affinity chromatography and two-dimensional SDS-PAGE. The protein was
      electrophoretically transferred to polyvinyl difluoride membranes which were
      stained with Coomassie blue R-250. The stained protein corresponding to ENDO-II
      (M(r) 28,000 to 32,000; pI 7.0 to 9.0) was cut from the membranes for amino acid
      sequencing. Partial amino acid sequence was determined by automated Edman
      degradation using a gas phase sequencer and phenylthiohydantoin analyzer.
      Sequence analysis of ENDO-II yielded 25 residues: C S C A P T H P Q T A F C N S D
      L V I R K F M G. Comparison to sequence databanks demonstrated significant
      homology with rat (100%) and human (84%) tissue inhibitor of metalloproteinases-1
      (TIMP-1). Western blot analysis using a TIMP-1 antibody confirmed amino acid
      sequence analysis. In conclusion, ENDO-II shares sequence homology with TIMP-1
      and cross-reactivity with TIMP-1 antibody and subsequently identifies production
      of TIMP-1 by endometriotic tissues. The synthesis and secretion of TIMP-1 by
      endometriosis may derange the normal proteolytic milieu of the peritoneal cavity
      and contribute to the etiology and underlying physiological sequelae associated
      with the disease endometriosis.

PMID- 8530637
TI  - Insulin action in human granulosa cells from normal and polycystic ovaries is
      mediated by the insulin receptor and not the type-I insulin-like growth factor
      receptor.
AB  - In order to account for the effects of insulin on the polycystic ovary (PCO),
      despite peripheral insulin resistance in women with polycystic ovary syndrome
      (PCOS), it has been suggested that insulin may act through the type-I insulin
      like growth factor (IGF) receptor and not the insulin receptor. We have tested
      this hypothesis by investigating the effect of anti-insulin receptor and anti
      type-I IGF receptor antibodies on insulin-stimulated steroidogenesis in human
      granulosa cells in vitro from normal (N) and PCO. Insulin-stimulated estradiol
      and progesterone production was inhibited by an anti-insulin receptor antibody.
      In contrast, anti-type-I IGF receptor antibodies had no effect on insulin
      stimulated steroidogenesis in granulosa cell cultures from N or PCO. Hence
      insulin acts via its own receptor in human granulosa cells from both N and PCO.

PMID- 8530638
TI  - Ovulation induction. Effects of ovulation induction with gonadotrophins on the
      ovary and uterus and their implications for assisted reproduction.

PMID- 8530639
TI  - Ovulation induction in 1995: a new policy.

PMID- 8530640
TI  - Follicular selection in the cyclic hamster: a 1960 model.

PMID- 8530641
TI  - Regulation of ovarian androgen production: a key parameter to success during
      ovarian stimulation?

PMID- 8530642
TI  - The effects of ovulation induction with gonadotrophins on the ovary and uterus
      and implications for assisted reproduction.

PMID- 8530643
TI  - The effects of natural and synthetic sex steroids on human decidual endothelial
      cell proliferation.
AB  - The effects of natural and synthetic sex steroids on the proliferation of human
      decidual capillary endothelial cells in culture were investigated. Oestradiol at
      5.0 ng/ml stimulated culture growth. Lower concentrations of oestradiol inhibited
      growth, while higher concentrations had no effect. Low concentrations of
      progesterone (5.0 and 10.0 ng/ml) had no effect on growth, while higher
      concentrations (20.0 and 40.0 ng/ml) inhibited growth. Combinations of oestradiol
      and progesterone usually reproduced the effects of progesterone alone. 3
      Ketodesogestrel and levonorgestrel both inhibited endothelial cell growth, while
      medroxyprogesterone acetate had no effect. These findings suggest that (i)
      oestradiol and progesterone have direct effects on endothelial cells and are
      probably involved in the cyclical growth and regression of endometrial blood
      vessels in vivo, and (ii) the actions of certain progestogen-only contraceptives
      may have direct effects on endometrial blood vessels.

PMID- 8530644
TI  - Induction of pre-ovulatory gonadotrophin surge with gonadotrophin-releasing
      hormone agonist compared to pre-ovulatory injection of human chorionic
      gonadotrophins for ovulation induction in intrauterine insemination treatment
      cycles.
AB  - The clinical outcome of intrauterine insemination (IUI) treatment cycles
      employing a gonadotrophin-releasing hormone agonist [GnRHa, triptorelin
      (Decapeptyl)] or human chorionic gonadotrophin (HCG) for ovulation induction was
      compared. A group of 48 patients presenting with amenorrhoea, oligomenorrhoea or
      unexplained infertility were all treated with human menopausal gonadotrophins
      (HMG) from day 5 of the cycle, on an individualized schedule. They were then
      randomly divided into two groups to receive either a single s.c. injection of 0.1
      mg triptorelin or a single i.m. injection of 10,000 IU HCG after follicular
      maturation. IUI was performed approximately 24 and 48 h following the injection.
      A transitory increase in serum luteinizing hormone and follicle stimulating
      hormone concentrations was achieved following injection of GnRHa. A total of 24
      patients received 72 treatment cycles with GnRHa, producing 11 conceptions
      (15.3%) and two abortions (18.2%), resulting in a term pregnancy rate of 13.6%.
      There were four cases of grade 3-4 ovarian hyperstimulation syndrome (OHSS), two
      of which were conception cycles. In all, 24 patients underwent 68 cycles treated
      with HCG, producing 18 conceptions (26.5%) and six abortions (33.3%), resulting
      in a term pregnancy rate of 19.0%. There were eight cycles of grade 3-4 OHSS, two
      of which were conception cycles. These results show that an s.c. injection of a
      relatively low dose of GnRHa can be as effective as HCG in producing pregnancy in
      IUI treatment cycles.

PMID- 8530645
TI  - Insulin-like growth factor binding proteins in a natural pre-ovulatory follicle
      from a woman with polycystic ovary syndrome.
AB  - Insulin-like growth factor binding protein (IGFBP) concentrations in the
      follicular fluid of ovarian follicles have been shown to correlate with dominance
      and atresia. IGFBP-2 and IGFBP-4 are increased in atresia, and IGFBP-3 is
      decreased in dominant follicles. The purpose of this study was to compare the
      IGFBP concentration in follicular fluid from a natural pre-ovulatory follicle of
      a woman with polycystic ovarian syndrome (PCOS) with other PCOS follicles and
      dominant follicles from normally cycling women. Follicular fluid was collected
      from 5-7 mm diameter follicles and a natural pre-ovulatory follicle from women
      with PCOS, and healthy and atretic follicles from normal women. The IGFBP
      profiles were analysed using Western ligand blotting. The IGFBP concentrations in
      the 5-7 mm diameter follicles from the polycystic ovaries containing a pre
      ovulatory follicle were similar to those in follicles from other women with PCOS,
      and comparable with androgenic cohort follicles from normal women. In particular,
      the IGFBP-2 and IGFBP-4 concentrations were elevated significantly compared with
      the oestrogenic cohort follicles. The concentrations of all IGFBP detected in the
      follicular fluid from the PCOS pre-ovulatory follicle were significantly less
      than those of the 5-7 mm diameter follicles from the same subject. The IGFBP
      concentrations were within the range of normal dominant follicles, and IGFBP-2
      and IGFBP-3 were at the lower end of the normal range. The results indicate that
      the PCOS pre-ovulatory follicle contained a normal pattern of IGFBP expression
      even though the other follicles exhibited a pattern typical of PCOS. These data
      support the hypothesis that decreased concentrations of IGFBP, in particular
      IGFBP-3, may be involved in selection of the dominant follicle, and that when a
      spontaneous pre-ovulatory follicle develops in PCOS, the underlying cause of the
      polycystic ovaries is not resolved but the rest of the ovary remains polycystic.

PMID- 8530646
TI  - Effect of opioid blockade on insulin metabolism in polycystic ovarian disease.
AB  - A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to
      evaluate the involvement of endogenous opioids in the pathophysiology of the
      hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist.
      An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the
      cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose,
      insulin and connecting peptide (c-peptide) concentrations were evaluated in all
      samples. Based on their insulinaemic response to OGTT, patients were classified
      as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P
      < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group
      without affecting the c-peptide incremental area; in the normoinsulinaemic group
      there was a slight, but not significant, increase in both c-peptide and insulin
      incremental areas. The two groups showed similar c-peptide incremental areas
      after naltrexone treatment. There was no significant difference in the c
      peptide:insulin incremental areas molar ratio between the two groups; after
      treatment, a significant increase in this ratio was observed in both groups. When
      we considered the data as an expression of the fractional hepatic extraction of
      insulin, we found a lower value for hyperinsulinaemic in comparison with
      normoinsulinaemic patients (not significant), and a significant (P < 0.01)
      improvement of this parameter in the hyperinsulinaemic group after naltrexone
      administration. In conclusion, we suggest that the contribution to
      hyperinsulinaemia in PCOD patients may be at least in part due to both increased
      pancreatic secretion and reduced hepatic removal of insulin. Chronic
      pharmacological inhibition of opioid tone could improve the insulin plasma
      concentration by acting chiefly on the liver metabolism of insulin in
      hyperinsulinaemic patients.

PMID- 8530647
TI  - Subjects with polycystic ovaries without hyperandrogenaemia exhibit similar
      disturbances in insulin and lipid profiles as those with polycystic ovary
      syndrome.
AB  - Polycystic ovaries (PCO) are detected using ultrasonography in a proportion of
      women who do not have clinical symptoms of the polycystic ovary syndrome (PCOS).
      The aim of this study was to compare the metabolic and endocrine differences
      between women with such ultrasound-detected PCO and women with PCOS, and to
      relate these changes to clinical presentation with particular reference to cycle
      irregularity. A group of 118 women showing PCO on vaginal ultrasound scan was
      divided into those who had no hyperandrogenaemia (n = 21) and those who had
      increased androgens and a clinical presentation normally associated with PCOS (n
      = 97). These were compared with a reference group of 26 normal subjects. Glucose
      tolerance, lipid concentrations and endocrine profiles were compared between
      groups. Apart from higher concentrations of androgens in the PCOS group, there
      were no significant differences between the PCO and PCOS groups in either fasting
      and stimulated insulin and glucose or in concentrations of sex hormone-binding
      globulin, gonadotrophins and blood lipids or in ovarian volume. Both PCO and PCOS
      subjects with cycle irregularity had significantly higher concentrations of serum
      fasting and stimulated insulin independent of androgens and body mass index than
      those with normal cycles. It was concluded that: (i) PCO and PCOS patients have
      equivalent disturbances in relation to insulin and glucose metabolism as well as
      lipid and lipoprotein disturbances compared to reference subjects; (ii) higher
      serum insulin values are associated with menstrual irregularity in both groups;
      (iii) ultrasound evidence for PCO predicts similar metabolic sequelae to PCOS and
      can therefore be used for studies of the genetics and long term risks for this
      condition.

PMID- 8530648
TI  - The empty follicle syndrome: a pharmaceutical industry syndrome.
AB  - The purpose of this study is to provide evidence that empty follicle syndrome
      (EFS) is a result of an abnormality in the in-vivo biological activity of some
      batches of commercially available human chorionic gonadotrophin (HCG). This is a
      comparative study between six consecutive in-vitro fertilization (IVF) cases with
      EFS (study group) and 10 IVF pregnancy cycles (control group). Both groups
      received the same ovarian stimulation protocol consisting of leuprolide acetate
      and human menopausal gonadotrophin (HMG). An i.m. injection of 10,000 IU of HCG
      was administered once follicles had reached 18-20 mm and oestradiol/follicle > or
      = 16 mm was at least 900 pmol/l. Transvaginal aspiration was performed 36 h
      later. Plasma HCG prior to and 12 h after i.m. injection as well as the
      follicular fluid (FF) concentrations of oestradiol, progesterone, luteinizing
      hormone (LH) and HCG were determined in the study group and controls. The in
      vitro biological activity of the batch of HCG used by the EFS cases and the
      control group was determined using a Leydig cell preparation from adult rats.
      Furthermore, the plasma clearance rate after i.v. injection of 5000 IU of HCG,
      from the same batches, was studied in three male volunteers. In the IVF cycles,
      no HCG was detected in plasma prior to the injection of commercial HCG. After 12
      h, no HCG was detected in the study group compared to a mean of 207.5 IU/l (110
      360) in controls. Mean FF concentration of LH, HCG, progesterone and oestradiol
      was 0.9 IU/l, 0 IU/l, 3.1 nmol/ml and 4.4 nmol/ml in EFS compared to 1.0, 98.3,
      32.0 and 3.7 in pregnancy cycles. The in-vitro biological activity in both HCG
      batches was not significantly different; however, immunoreactive HCG used in EFS
      cases was undetectable in plasma of male volunteers as soon as 10 min after i.v.
      injection of 5000 IU of HCG. The endocrine abnormalities found in follicular
      fluids of EFS are not a consequence of an ovarian problem but the result of a
      lack of exposure to biologically active HCG. The rapid clearance of the drug
      after i.v. injection and the high affinity of desialylated HCG to liver cells
      suggest this to be a possible explanation for this infrequent but unfortunate
      event.

PMID- 8530649
TI  - Pre-ovulatory oxytocin administration promotes the onset of the luteinizing
      hormone surge in human females.
AB  - Luteinizing hormone (LH) secretion during the ovulatory cycle is believed to be
      predominantly regulated by gonadotrophin-releasing hormone. Investigations in
      animals have strongly suggested that oxytocin also participates in LH control and
      the physiological events controlling LH surge initiation. In the human female,
      however, there has been no evidence supporting oxytocin's involvement in the
      processes leading to ovulation. In this study the effect of a preovulatory
      infusion of oxytocin on the onset of the LH surge was investigated in women aged
      20-35 years who had natural ovulatory menstrual cycles of lengths between 25-35
      days. Vaginal ultrasound scanning monitored follicular growth during the late
      follicular phase. When a follicle > 14 mm in diameter was observed each woman was
      randomized into one of two groups. One group (n = 8) received an oxytocin
      infusion of 256 mIU/min for 2 h, the other group (n = 8) received normal saline.
      The women who were administered oxytocin at this late follicular stage had an
      earlier onset of the LH surge than those who had received saline (P < 0.01). The
      results indicate that oxytocin promotes the onset of the LH surge in humans.

PMID- 8530650
TI  - Failure of oestrogen induced luteinizing hormone surge in women treated with
      mifepristone (RU 486) every day for 30 days.
AB  - It has been demonstrated previously that administration of the antiprogestin
      mifepristone (RU 486; 1-5 mg daily) inhibits or delays both the pre-ovulatory
      luteinizing hormone (LH) surge and ovulation. To investigate this mechanism,
      dynamic tests of pituitary ovarian function were performed in six healthy women
      before and during the administration of mifepristone (2 mg daily for 30 days). On
      day 9 of the control and treatment cycles, samples of blood were collected every
      15 min over 12 h for measurement of LH concentration. After 10 h, the
      responsiveness of the pituitary was tested by the i.v. injection of 10 micrograms
      of gonadotrophin-releasing hormone (GnRH). On day 10 of the control and treatment
      cycles, two patches releasing 200 micrograms/day of oestradiol were applied to
      skin on the abdomen for 3 days. Blood was collected at 24, 48, 59, 72, 81 and 96
      h after application of the oestrogen patches for the measurement of gonadotrophin
      and ovarian hormone concentrations. Follicular development continued in all women
      during their treatment with mifepristone, and ovulation was suppressed (four
      women) or delayed (two women). There was no significant difference in the basal
      concentration of LH between the control and treatment cycles (mean +/- SE; 5.5 +/
      0.4 versus 7.7 +/- 0.4 IU/l respectively), or in the frequency (interpulse
      interval, 101 +/- 12 versus 105 +/- 13 min respectively) and the amplitude (2.1
      +/- 0.4 versus 2.6 +/- 0.4 IU/l respectively) of LH pulses. The response to GnRH
      was similar. On day 10, the basal concentrations of LH, follicle-stimulating
      hormone (FSH), prolactin, oestradiol and progesterone and the diameter of the
      dominant follicle (15.7 +/- 1.8 versus 13.3 +/- 1.9 mm) were similar during
      control and treatment cycles. In control cycles, there were significant increases
      in the concentrations of LH and FSH within 72 h of application of the oestrogen
      patches. During treatment cycles, concentrations of FSH and LH remained low, and
      were significantly lower than the values observed during control cycles (P <
      0.006). We conclude that the antiprogestin mifepristone disrupts ovulation by
      inhibiting the positive feedback effect of oestrogens and, hence, prevents or
      delays the generation of a pre-ovulatory LH surge.

PMID- 8530651
TI  - Gonadotrophins and prolactin rise after bilateral oophorectomy for benign
      conditions.
AB  - The aim of this study was to analyse the changes in follicle stimulating hormone
      (FSH), luteinizing hormone (LH) and prolactin concentrations in the 3 months
      following oophorectomy in pre-menopausal women operated on for benign
      gynaecological conditions. Included in this analysis were 21 women (mean age 47
      years, range 46-52) who underwent bilateral oophorectomy plus hysterectomy for
      fibroids or ovarian cysts. Plasma concentrations of FSH, LH and prolactin were
      measured before and on days 2, 4, 6, 14 and 30 after surgery; in 10 cases
      measurements were made on day 60, and in five cases on day 90 after surgery.
      Hormone concentrations were measured in duplicate daily samples, and
      immunoenzymatic assay kits were used for all the immunoassays. The FSH and LH
      concentrations increased constantly after surgery. Mean prolactin concentrations
      also increased from 12.1 ng/ml before surgery to 31.5 ng/ml on day 14 after
      bilateral oophorectomy, but decreased thereafter to 18.2 ng/ml on day 30, 10.9
      ng/ml on day 60 and 6 ng/ml on day 90. In conclusion, transient (2-3 weeks)
      increased prolactin concentrations are observed after surgical castration.

PMID- 8530652
TI  - Outcome of pregnancy in women with recurrent spontaneous abortion following
      immunotherapy with allogeneic lymphocytes.
AB  - The efficacy of immunotherapy in the prevention of habitual abortion remains
      controversial. It has been suggested that the benefits are predominantly due to
      psychological factors. We have evaluated the success of pregnancy outcome
      following immunotherapy with allogeneic lymphocytes, in relation to the
      subsequent development of anti-paternal cytotoxic antibodies (APCA). It was
      observed that in women who developed an APCA titre of > or = 1:16, live births
      occurred in 16 out of 21 cases (76%), while only two out of seven (28%) women who
      failed to achieve an APCA titre of > or = 1:16 had successful pregnancies (P <
      0.05). In eight women who had an APCA titre of 1:16 on initial screening, and
      were, therefore, excluded from the trial, successful pregnancy outcome was noted
      in 62.5% of cases. Although these results are based on a small sample and on an
      open, non-randomized trial, they show that the efficacy of immunotherapy is
      related to immune response to allogeneic lymphocytes, and is not simply a placebo
      effect. Measurement of APCA titre could serve as a marker for immunopotentiation.

PMID- 8530653
TI  - Bone marrow-derived cell populations in uterine and ectopic endometrium.
AB  - Uterine endometrium contains numerous bone marrow-derived cells. The spectrum of
      cell types is different from that of any other tissue, and the differences in
      endometrium from women with endometriosis may reflect a different endometrial
      phenotype in these women. The cell types of bone marrow origin found in ectopic
      endometrium may indicate the degree of differentiation of the tissue. It was
      found that, in normal endometrium, the CD45+ cell population comprised T cells,
      macrophages, CD56+ large granular lymphocytes, some CD16+ cells and a few B
      cells. Changes in these cell populations during the menstrual cycle were similar
      in endometrium from both controls and patients with endometriosis, and resembled
      that reported previously by others. In ectopic endometrium, the frequency of
      CD45+ cells remained within the same range as that of uterine endometrium but
      without any obvious pattern of change during the menstrual cycle. CD56+ large
      granular lymphocytes, an immune cell type characteristic of uterine endometrium,
      were also found in ectopic endometrium. Our results indicate that ectopic
      endometrium, as well as comprising both glandular and stromal cells, contains
      bone marrow-derived cell populations similar to those of uterine endometrium.
      This suggests that the same processes of cell migration and/or differentiation
      occur in ectopic and uterine endometrium.

PMID- 8530654
TI  - Experimental model for neoangiogenesis in adhesion formation.
AB  - This study presents an animal model for the observation of adhesion formation,
      from a vascular viewpoint. In 60 Wistar rats, a 4 cm midline incision was made
      and a 0.5 cm square piece of silastic 0.2 mm thick was fixed on the right side of
      the peritoneum with two separate angular stitches of nylon 9/0. The rats were
      randomized in six groups of 10 animals and were operated on again on days 2, 4,
      6, 8, 10 and 12 respectively. Biopsies for scanning electron microscopy were
      obtained by resecting a 2 x 2 cm square of parietal peritoneum around and
      covering the silastic patch. Foreign body reaction induced by the silastic patch
      and ischaemia caused by stitching are the stimuli for adhesion formation. The
      results showed a gradual progression in the type and tenacity of adhesion
      formation. The maximal degree of peritoneal reactive angiogenesis was noted
      between days 8 and 12, together with a decrease and a redistribution in the
      extent of adhesions. In the early stages, vascularization is part of the
      organization of adhesions while their extent is limited. Two parallel mechanisms
      take part in trauma healing: while omento-parietal adhesions are vascularized,
      new peritoneal tissue with its vascular network develops and covers the silastic
      surface and the traumatized area. This theory is supported by the presence of
      fibroblasts differentiating into mesothelial cells on day 8. Theoretically, a
      valid treatment in preventing adhesion formation should increase the peritoneal
      neoangiogenesis and the repair of peritoneal lesions, but at the same time
      prevent the vascularization of adhesions. The present model offers the
      possibility of testing the effect of any treatment or device for preventing post
      operative adhesions in a relatively short time.

PMID- 8530656
TI  - The use of GDA-J/F3 monoclonal antibody for the detection of dead spermatozoa
      (necrosperm) during semen analysis.
AB  - The distinction between immotile necrosperm (dead spermatozoa) and those with
      immotility due to other causes is of the utmost clinical importance. The
      supravital dyes currently used for the identification of necrosperm are not
      highly reliable or accurate. In this study, GDA-J/F3 monoclonal antibody (MoAb)
      which reacts with the fibrous sheath (FS) was used as a specific probe for the
      detection of necrosperm using indirect immunofluorescence (IIF). Previously,
      several lines of evidence indicated the reaction of the antibody with necrosperm.
      This was confirmed in the current study where GDA-J/F3 MoAb failed to react with
      viable swim-up separated spermatozoa; such cells were only stained following
      sperm demembranation with 1% Triton X-100. Furthermore, by using immunogold
      electron microscopy of a normozoospermic sperm sample, all the spermatozoa which
      reacted with GDA-J/F3 MoAb showed damaged cytoplasmic membranes. Following these
      initial studies, sperm samples were obtained from 42 men attending infertility
      clinics and assessed by conventional semen analysis and GDA-J/F3 MoAb screening
      using IIF. The results showed a wide variation in sperm immotility and GDA-J/F3
      reactivity; the ranges were 19-99 and 0-50% respectively. This novel
      immunological approach provides a simple and specific method of necrosperm
      enumeration for the investigation of male infertility.

PMID- 8530655
TI  - Deleterious effects of khat addiction on semen parameters and sperm
      ultrastructure.
AB  - The semen parameters and sperm ultrastructural morphology have been described in
      semen samples from two groups of Yemeni subjects. The first 'exposed' group
      comprised 65 khat addicts, while the second control group included 50 non-khat
      addict subjects. The mean age was 39.94 +/- 13.85 and 35.72 +/- 11.35 years in
      the exposed and control groups respectively, without a significant difference.
      The mean duration of khat addiction among the addicts was 25.34 +/- 12.96 years
      (range 6.00-48.00). Statistically significant differences were detected between
      the semen parameters of the two groups. Such parameters, including semen volume,
      sperm count, sperm motility, motility index and percentage of normal spermatozoa,
      were lower among addicts. Significant negative correlation was also found between
      the duration of khat consumption and all semen parameters (r ranged from -0.30 to
      -0.74). At the transmission electron microscopy level, a counting system was
      incorporated to compare the numbers of normal spermatozoa with deformed and dead
      spermatozoa in ultrathin plastic sections. The total mean percentage of deformed
      spermatozoa was approximately 65%. Different patterns of sperm deformation were
      demonstrated, and included both the head and flagella in complete spermatozoa,
      aflagellate heads, headless flagella and multiple heads and flagella. Deformed
      heads showed aberrated nuclei with immature nuclear chromatin and polymorphic
      intranuclear inclusions; these were associated with acrosomal defects. The
      deformed flagella demonstrated numeric aberrations of the axonemal 9 + 2
      configuration and structural defects of their associated elements. Persistent
      cytoplasmic droplets were observed frequently. This study has shown for the first
      time the deleterious effects of khat addiction on semen parameters in general and
      sperm morphology in particular of all addicts, especially those who have consumed
      khat for longer periods of time.

PMID- 8530657
TI  - Pregnancy results from a vibrator application, electroejaculation, and a vas
      aspiration programme in spinal-cord injured men.
AB  - In an infertility treatment programme for spinal-cord injured men, vibrator
      application was primarily used in cases of upper motor neurone lesion and
      electroejaculation in men with lower lesions, or when vibrator application failed
      to induce ejaculation. Spermatozoa were obtained by these methods from 29 out of
      35 men who desired infertility treatment. No ejaculate was obtained from six men.
      Three of these men plus two others with very poor sperm quality with
      electroejaculation underwent micro-surgical sperm aspiration from the vas
      deferens for invitro fertilization (IVF), and spermatozoa were obtained from all
      of them. Thus it was possible to obtain spermatozoa from almost every spinal-cord
      injured man who had ongoing spermatogenesis using these three methods.
      Insemination was the primary infertility treatment used with all the couples
      where there was successful ejaculation. In all, 12 pregnancies resulted from home
      vaginal inseminations, eight from intrauterine inseminations, two from IVF with
      ejaculated spermatozoa, and two from IVF with spermatozoa aspirated from the vas.
      Three couples had children from donor inseminations (not counted in the results);
      12 are still in the programme. From 24 pregnancies, 22 children have now been
      born to 18 couples out of the original 35 (51%), and there were four abortions.
      Hence, overall, infertility treatment of spinal-cord injured men has given good
      results.

PMID- 8530658
TI  - Pentoxifylline-supplemented cryoprotectant improves human sperm motility after
      cryopreservation.
AB  - In this study, human spermatozoa obtained from donors (n = 15) with normal semen
      characteristics were cryopreserved in human sperm preservation medium,
      supplemented with the phosphodiesterase inhibitor pentoxifylline at
      concentrations of 0, 1, 3 and 10 mM. The effect of pentoxifylline on
      cryopreserved spermatozoa was determined by monitoring changes in sperm motility
      and acrosome morphology by labelling the spermatozoa with fluorescein-conjugated
      concanavalin A lectin. Cryoprotectant supplemented with 1 mM pentoxifylline was
      found to improve post-thaw progressive motility from 15.3 +/- 2.4 (control) to
      23.1 +/- 3.8% (P < 0.01), and total motility from 27.4 +/- 3.3 (control) to 38.2
      +/- 3.9% (P < 0.05) without reducing the percentage of spermatozoa with normal
      acrosomal regions, and so appears useful for cryopreservation purposes. The
      beneficial effects of 1 mM pentoxifylline on sperm motility were shown to be
      maintained post-thaw over a 6 h time course. Cryoprotectant supplemented with 3
      mM pentoxifylline was found to improve only post-thaw progressive motility, from
      15.3 +/- 2.4 (control) to 20.7 +/- 3.0% (P < 0.05). However, cryopreservation in
      the presence of 10 mM pentoxifylline was found to have a significantly (P < 0.01)
      detrimental effect on acrosome morphology post-thaw, reducing it from 29.0 +/-
      2.0 (control) to 21.0 +/- 2.4% without affecting sperm motility. This suggests
      that assessment of the acrosomal region may indicate subtle deleterious effects
      of cryoprotectant supplements that cannot be determined from post-thaw motility
      assessments alone. These findings differ from previous studies in that a lower
      concentration of pentoxifylline (1 mM) was found to be optimal for
      cryopreservation purposes.

PMID- 8530659
TI  - Prediction of ovarian cycle outcome by follicular characteristics, stage 1.
AB  - Both dominant and subdominant follicles have been identified and individually
      monitored over the follicular phases of 54 natural cycles in 36 women. Population
      dynamics of all antral follicles, visible by ultrasonography, in the ovary over
      the entire cycle have also been characterized for the first time. This has been
      accomplished by developing a new system of mapping and monitoring follicles,
      including a three-dimensional computer imaging model and correlation program. The
      different dominant follicle types were characterized by their ultrasonographic
      properties. Ovulatory follicles were rounded in shape and mid-range echogenic,
      with a smooth antral edge by late follicular phase. Luteinized unruptured
      follicles were round, had low echogenicity and a very smooth antral edge. Atretic
      follicles were irregular in shape and antral edge and had mid-range echogenicity.
      A further important finding was that follicle success appears to be related to
      timing of growth and to the subdominant follicle population present in the ovary.
      An analysis of follicle population dynamics in ovulatory cycles showed a drastic
      decrease in number at the end of the luteal phase, followed by a sharp increase
      at the beginning of the follicular phase. This study has demonstrated that
      characteristics of individual follicles and population dynamics of both dominant
      and subdominant follicles are strongly associated with cycle outcome. These
      findings will contribute towards a predictive model of dominant follicle status
      and cycle outcome. A new hypothesis of follicle competition has also been
      proposed.

PMID- 8530660
TI  - Interaction between oxytocin and prostaglandin F2 alpha in human corpus luteum?
AB  - The effect of a single injection of oxytocin into the corpus luteum, with or
      without pretreatment with a prostaglandin synthetase inhibitor, was studied in
      order to investigate possible local interactions between prostaglandin (PG)F2
      alpha and oxytocin in the regulation of the human corpus luteum. Oxytocin (4 IU)
      was injected through the abdominal wall into the corpus luteum in women
      undergoing laparoscopy for legal sterilization. In the control cases, saline was
      injected into the corpus luteum, or oxytocin was injected into the contralateral
      ovary. Oxytocin injected into the corpus luteum caused a fall in serum
      progesterone and shortened the luteal phase. These effects were not seen
      following injection of saline into the corpus luteum, or following injection of
      oxytocin into the contralateral ovary. After the injection of oxytocin into the
      corpus luteum a rise in 15-keto-dihydro-PGF2 alpha, a PGF2 alpha metabolite, was
      seen. The changes in serum progesterone caused by injection of oxytocin into the
      corpus luteum could be prevented if a PG synthetase inhibitor was given before
      the injection. These findings suggest that local interaction between oxytocin and
      PGF2 alpha plays a role in the regulation of the human corpus luteum.

PMID- 8530661
TI  - Folliculocentesis: a novel research technique to investigate the intrafollicular
      endocrine microenvironment.
AB  - During development of the dominant follicle, the avascular granulosa cells and
      oocyte are exposed to the follicular fluid endocrine microenvironment. An
      alteration in the endocrine characteristics of follicular fluid affects
      follicular steroidogenesis, oocyte maturation, ovulation and subsequent corpus
      luteum function. In-vitro studies on pooled follicular fluid from ovarian
      specimens lacked temporal precision between menstrual and follicular endocrine
      events. We have established a new technique, termed folliculocentesis (FC), to
      sample follicular fluid from the dominant ovarian follicle without compromising
      its growth or function during the mid- to late follicular phase. A total of 38
      subjects with regular ovulatory cycles each underwent two identical cycles of
      hormone and follicle growth monitoring: one cycle served as the control, and FC
      was performed during the second cycle. During all cycles, plasma luteinizing
      hormone (LH), oestradiol and ultrasound monitoring of follicle growth were
      commenced on day 7 and continued until after ovulation. During FC cycles, 200
      microliters of follicular fluid were aspirated from the dominant follicle using
      transvaginal ultrasound guidance when the follicle diameter reached > or = 10 mm.
      Six subjects were excluded from the study because of incomplete or invalid
      endocrine data. In all, 32 subjects completed both the FC and control cycles. The
      follicle growth pattern, maximum follicle diameter, plasma oestradiol, oestradiol
      peak, plasma LH, LH surge and follicular phase length were similar during FC and
      control cycles. A total of 50 valid follicular fluid samples were obtained when
      the dominant follicle was sampled once, twice or three times during the same
      cycle and from the same follicle in 15, 16 and one subjects respectively. The
      follicular fluid samples contained steroid concentrations consistent with those
      of the mid- to late follicular phase. We conclude that the FC procedure is safe,
      easy to perform and does not affect follicle growth or hormone dynamics. Analysis
      of the follicular fluid samples is expected to provide us with valuable in-vivo
      information about ovarian endocrinology.

PMID- 8530662
TI  - Follicular development in cryopreserved marmoset ovarian tissue after
      transplantation.
AB  - Pieces of marmoset ovary were frozen by slow cooling in 1.5 M dimethylsulphoxide.
      The follicles in fresh and frozen tissue were counted and examined for
      morphological appearance in stained serial sections. The proportion of normal
      follicles was similar in fresh tissue and frozen tissue examined immediately
      after thawing. Follicles at all stages of folliculogenesis up to the small antral
      stage survived freezing and thawing. Fresh and frozen tissue was transplanted
      underneath the kidney capsules of ovariectomized immunodeficient mice. The
      establishment of grafts was similar, and oestrogenic activity (cornification of
      the vaginal epithelium) was observed in the recipients 20 and 16 days after
      transplantation of fresh and frozen grafts respectively. The total number of
      follicles and the proportion of normal follicles were similar in fresh and frozen
      grafts. Grafts of frozen tissue recovered between 7 and 15 days after transfer
      contained follicles up to the small antral stage of development. Grafts recovered
      between 21 and 32 days contained follicles at all stages of folliculogenesis,
      including large antral follicles (1-2 mm diameter). Our results suggest that
      freezing and thawing do not substantially damage marmoset ovarian tissue, and the
      cryopreserved tissue retains its ability to support the development of large
      antral follicles.

PMID- 8530663
TI  - Morphometric characterization of normal and abnormal human zygotes.
AB  - Human zygotes (n = 278) from 96 in-vitro fertilization gonadotrophin-stimulated
      cycles were photographed in their pronuclear stage (16-18 h post-insemination).
      Normal morphological fertilization (two pronuclei) was observed in 215 zygotes,
      17 showed only one pronucleus, 40 showed three pronuclei and six showed four.
      Area, perimeter and maximum and minimum diameters of each zygote and pronucleus
      were measured using an IBAS 2000 (Kontron) image analyser. When the four groups
      were compared, whole zygotes did not show any morphometric difference. However,
      pronuclei from these groups showed that a high number of pronuclei was directly
      related to small pronuclei. Differences in pronuclear size and a linear increase
      in the nucleus/cytoplasm relationship were found which varied with the number of
      pronuclei.

PMID- 8530664
TI  - Recurrent failure in polar body formation and premature chromosome condensation
      in oocytes from a human patient: indicators of asynchrony in nuclear and
      cytoplasmic maturation.
AB  - All oocytes from a patient who had undergone four unsuccessful in-vitro
      fertilization attempts showed neither a polar body nor pronuclei when examined
      for fertilization. In 19 inseminated oocytes that were spread for karyotypic
      analysis, one haploid set of metaphase II chromosomes and a remarkable condensed
      structure were found. Hormonal and morphological criteria implied that the
      oocytes had been mature at the time of retrieval. Since non-inseminated oocytes
      contained only one set of metaphase II chromosomes, the condensed structure
      appeared to represent the sperm chromatin in the state of premature chromosome
      condensation due to a block in oocyte maturation. Since the first and second
      polar body, as well as their chromatin, were undetectable in all the patient's
      oocytes, a rapid maturation to metaphase II before retrieval and prolonged arrest
      in this state before fertilization, accompanied by degeneration of the first
      polar body, appear to be responsible for the condition. In accordance with this
      notion, degenerate spindles (typical of post-ovulatory aged oocytes) and
      separating chromosomes (probably representing presegregating chromatids) were
      observed by antitubulin immunofluorescence.

PMID- 8530665
TI  - Consequences of non-extrusion of the first polar body and control of the
      sequential segregation of homologues and chromatids in mammalian oocytes.
AB  - Absence of polar body formation, or premature chromatin condensation (PCC) in
      human oocytes can cause infertility. We studied in-vitro maturing mouse oocytes
      in order to identify risk factors for such conditions, and for the precocious
      segregation of homologues or chromatids. Treatment with the actin-binding drug
      cytochalasin D (10 micrograms/ml) arrested oocytes in metaphase I. Upon exposure
      to Ca(2+)-ionophores, anaphase I was triggered in the absence of cytokinesis.
      Chiasmata resolved and homologues separated instantaneously. In some oocytes
      predivision of all chromatids occurred. Homologues or chromatids never separated
      even after exposure to Ca(2+)-ionophores when microtubules were depolymerized,
      although bivalents could eventually decondense. Thus, in meiosis I checkpoints
      exist which ensure that homologue separation only takes place when a metaphase I
      spindle is present but cytokinesis and anaphase progression can be uncoupled.
      Cycloheximide induced a sequential separation of homologues in oocytes with
      intact metaphase I spindle, resulting in metaphase II chromosomes and bivalents
      in individual cells as also found in some human oocytes of aged females. In
      oocytes which progressed to metaphase II but failed to extrude a first polar
      body, the two sets of chromosomes eventually aligned on a common spindle
      ('diploid' metaphase II). PCC of one set was never observed. Ageing in vitro of
      cytochalasin D-blocked metaphase I oocytes had no pronounced effect on chromosome
      segregation.

PMID- 8530666
TI  - Ultrastructure of human cumulus oophorus: a transmission electron microscopic
      study on oviductal oocytes and fertilized eggs.
AB  - The aim of the present study was to assess the heterogeneity of cumulus cells
      that occurs in human cumuli associated with oviductal oocytes and fertilized
      eggs. Transmission electron microscopy was used to study the cumulus masses
      surrounding both unfertilized oocytes and fertilized eggs (a pronuclear and a 4
      cell stage) recovered at different intervals after ovulation. The specimens were
      obtained by flushing the oviducts of normal cycling women who underwent surgical
      sterilization. The cumuli were expanded due to large and irregular intercellular
      spaces; small linear gap junctions were seen at cell contacts, whereas annular
      gap junctions were found only in the cytoplasm of some cells. Both types of
      junction were less abundant in fertilized specimens. Cells surrounding fertilized
      eggs projected numerous long, thin microvilli into the intercellular spaces. As a
      rule, the inner layer of the cumulus mass (corona cells) was composed of cells
      whose surface was relatively smooth. Cumulus cells showed oval nuclei with one or
      more nucleoli. The cytoplasm of most cells possessed abundant organelles typical
      of steroidosynthesis: (i) mitochondria with tubular or villiform cristae; (ii) a
      well-developed smooth endoplasmic reticulum; and (iii) electron dense lipid
      droplets often surrounded by a few concentric membranes of smooth endoplasmic
      reticulum and/or in close contact with microtubules and microfilaments.
      Microperoxisome-like structures were also present. After fertilization, an
      enhancement of the steroidosynthetic characteristics occurred in the outer layers
      of the cumulus mass, but not in the corona cells, which still appeared capable of
      protidosynthesis. Together, these morphological features support the hypothesis
      that the cumulus of oviductal oocytes and particularly of fertilized eggs,
      luteinizes like parietal granulosa cells, generating a steroid hormonal micro
      environment in the oviduct which may affect fertilization and zygote
      segmentation. Cumulus cells showing spermiophagic activity, as well as activated
      macrophages, leukocytes and red blood cells, were also found in the cumulus mass.
      The macrophages may play a local role both by phagocytic activity and by
      modulating the steroid secretion of the neighbouring cumulus cells which occurs
      in the ovarian follicle and corpus luteum. In conclusion, the cumulus mass
      surrounding tubal oocytes and fertilized eggs appears to be a heterogeneous and
      dynamic system, in which the micro-environment for fertilization and early embryo
      development is provided by diverse cell populations in addition to the oviductal
      cells.

PMID- 8530667
TI  - Female age does not affect the capacity of human zona pellucida to bind
      spermatozoa.
AB  - The purpose of this study was to evaluate the effect of female age on the
      capacity of the zona pellucida to bind spermatozoa. A total of 1008 unfertilized
      oocytes obtained from 210 women (aged 21-43 years) participating in the in-vitro
      fertilization programme were tested using a hemizona assay. Spermatozoa taken
      from a cryopreserved pool of fertile donor specimens served as a control in the
      hemizona assay, and were used to assess the ability of the zona pellucida to bind
      spermatozoa. The mean +/- SD number of spermatozoa attached to the hemizona was
      107 +/- 42. The binding capacity of different oocytes from the same cohort varied
      substantially (coefficient of variation = 28%). Age was not found to be
      correlated with the number of spermatozoa bound to the zona pellucida (r = -0.02;
      P > 0.1). It was concluded that female age has no role in the ability of the
      human zona pellucida to bind spermatozoa.

PMID- 8530668
TI  - Use of videocinematography to assess morphological qualities of conventionally
      cultured and cocultured embryos.
AB  - Videocinematography and image analysis procedures were utilized to evaluate the
      effect of conventional and coculture methodologies on morphological parameters in
      human embryos derived from in-vitro fertilization (IVF). Following 24-30 h of in
      vitro development, cocultured embryos had more acceptable morphological features
      and less fragmentation present than embryos cultured in medium alone. Cocultured
      embryos were more advanced at the time of replacement when compared with
      conventionally cultured embryos. Zona pellucida variation (> or = 20%) also
      occurred more frequently in cocultured embryos. The morphological characteristic
      most enhanced after coculture was blastomere expansion. Patients who became
      pregnant across both culture treatments had a higher proportion of
      morphologically normal embryos replaced than patients who failed to achieve an
      ongoing pregnancy. Clinical pregnancy rate for patients following coculture was
      49%, which was greater (P < 0.05) than the 29% detected for patients with embryos
      in the conventional culture group.

PMID- 8530669
TI  - The effect of testosterone on the maturation and developmental capacity of murine
      oocytes in vitro.
AB  - A dose-dependent inhibition of meiotic maturation and embryonic development was
      observed in both cumulus-enclosed and cumulus-denuded murine oocytes following
      incubation in the presence of 10, 20, 40, 60 and 80 microM testosterone for 18 h
      in vitro. Maturation to metaphase II was enhanced in cumulus-enclosed oocytes
      following maturation in the presence of human pre-ovulatory mural granulosa
      cells. However, maturation of cumulus-denuded oocytes was enhanced only when
      oocytes were cultured on a monolayer of human polycystic ovarian granulosa cells.
      The presence of cumulus cells had a significantly positive effect on both oocyte
      maturation (P = 0.002) and embryonic development (P < 0.001). In addition, the
      presence of follicular cells during maturation improved the number of fertilized
      oocytes reaching the blastocyst stage. These data indicate that the exposure of
      immature murine oocytes to testosterone during maturation significantly reduces
      their ability to mature and undergo normal embryonic development.

PMID- 8530670
TI  - Effects of embryo density and co-culture of unfertilized oocytes on embryonic
      development of in-vitro fertilized mouse embryos.
AB  - We have evaluated the effects of embryo density and the co-culture of
      unfertilized (degenerating) oocytes on the development of in-vitro fertilized
      (IVF) mouse embryos. In experiment 1, groups of one, five, 10 or 20 zygotes were
      cultured in 20 microliter drops of modified human tubal fluid (HTF) medium for
      168 h at 38.7 degrees C in 5% CO2 and 95% air. As the embryo density increased,
      significantly (P < 0.05) higher rates of embryos reached hatched blastocyst
      stage. In addition, the time required for hatching after IVF was significantly (P
      < 0.05) shortened by the increase in embryo density. In experiment 2, 10 IVF
      zygotes were cultured with or without 10 unfertilized (degenerating) oocytes in
      20 microliter drops of HTF medium. The rates of IVF embryos that developed to
      morula, blastocyst, expanded blastocyst and hatched blastocyst stages were
      decreased significantly (P < 0.01) by culturing embryos with unfertilized oocytes
      compared with culturing embryos alone. In experiment 3, groups of one or 10 IVF
      zygotes or 10 IVF zygotes plus 10 unfertilized oocytes were cultured in 20
      microliter drops of HTF medium and the number of cells per blastocyst was
      examined at 120 h after IVF. Increasing embryo density resulted in a significant
      (P < 0.05) increase in the number of cells per blastocyst. In contrast, the cell
      number of IVF embryos that developed to blastocyst decreased significantly (P <
      0.05) when they were cultured with unfertilized oocytes. The results suggest that
      in-vitro development of IVF mouse embryos is enhanced by increasing embryo
      density and is impaired by co-culture with unfertilized (degenerating) oocytes.

PMID- 8530671
TI  - A simple technique to quantify human sperm-zona pellucida binding assays.
AB  - A simplified method for assessing the degree of sperm-zona pellucida binding was
      developed. The zonae pellucidae of salt-stored, failed-fertilized human oocytes
      were each inseminated with between 1 x 10(5) and 1 x 10(6) motile spermatozoa/ml,
      prepared by a direct swim-up method from 11 individuals with normal sperm counts,
      as defined by the World Health Organization. Following 4 h of incubation at 37
      degrees C in humidified air, the zonae pellucidae were 'washed' by vigorous
      pipetting to remove any loosely attached spermatozoa. The zonae were then placed
      individually in microwells and dissolved by exposure to acidified (pH < 2.0)
      medium to form a fluid monolayer. The slides were sealed and the number of
      spermatozoa in the monolayer counted by each of three observers within 24 h.
      There was good agreement in the counts between the different observers, with a
      mean coefficient of variation of only 7.4% and a range of 1.8-16.7%. It was
      notable that the highest coefficients of variation occurred at the extremes of
      sperm numbers and that the results were stable overnight. The method is also able
      to identify observer bias within this variation, indicating the potential for
      improvements in assay performance. The technique reported has the advantage over
      current sperm-zona pellucida binding assays of allowing the determination of the
      precise number of spermatozoa bound to a zona pellucida while producing a slide
      which remains stable overnight.

PMID- 8530672
TI  - The effect of local intrauterine levonorgestrel administration on endometrial
      thickness and uterine blood circulation.
AB  - To evaluate non-invasively the role of levonorgestrel releasing devices in direct
      contact with the endometrium on menstrual spotting and endometrium inactivation,
      we inserted levonorgestrel releasing devices (20 micrograms/24 h) either into the
      cervical canal or the uterine cavity of 30 fertile women. Both before insertion
      and over the following 3 months, we used transvaginal sonography to measure the
      endometrial thickness in 20 of the women and Doppler flow to measure the uterine
      blood flow in the remaining 10 women. The women were asked to keep records of
      menstrual bleeding and they gave blood samples for the measurement of serum
      oestradiol, progesterone and levonorgestrel. By 10 weeks after insertion there
      was a significant decrease in endometrial thickness in both groups. Intracervical
      levonorgestrel release allowed the endometrium to maintain cyclic changes,
      whereas direct intrauterine levonorgestrel release eliminated the cyclical
      changes. The total number of spotting days was significantly less (P = 0.0249) in
      the intracervical release group at 3 months; 1.2 +/- 0.6 versus 8.1 +/- 1.8 (mean
      +/- SE). There were no significant differences in hormone concentrations between
      the groups. The pulsatility index did not change significantly during the study.
      We concluded that the inactivation process of the endometrium can be monitored by
      transvaginal sonography and that locally administered levonorgestrel does not
      change circulatory conditions detectable by Doppler flow. Our results also
      suggest that the inactivation process of the endometrium is different between
      intracervical and intrauterine levonorgestrel administration and may explain the
      difference in the number of spotting days.

PMID- 8530673
TI  - Inhibition of human endometrial stromal cell proliferation by interleukin 6.
AB  - We investigated the ability of interleukin 6 (IL-6) to modulate human endometrial
      stromal cell growth in vitro. Stromal cell proliferation in response to treatment
      with varying concentrations of IL-6 was determined. Endometrial tissue was
      obtained from 10 normally cycling women during the secretory phase of their
      menstrual cycle. Treatment with IL-6 resulted in a dose- and cell-density
      dependent inhibition of endometrial stromal cell proliferation in vitro. The
      maximal inhibition was observed with 200 pg/ml of IL-6 and at a concentration of
      10(5) cells/well. During in-vitro culture, stromal cells produced low amounts of
      IL-6 and demonstrated the presence of IL-6 receptor. These data demonstrate that
      IL-6 acts as a growth-regulatory signal for human endometrial stromal cells. We
      postulate that IL-6 may contribute to the maintenance of homeostasis in normal
      endometrium and that perturbation of IL-6 mediated responses may play a role in
      disorders of the endometrium such as endometrial cancer and endometriosis.

PMID- 8530674
TI  - The three-dimensional organization of the smooth musculature in the ampulla of
      the human fallopian tube: a new morpho-functional model.
AB  - The three-dimensional organization of the smooth musculature around the human
      ampulla is revealed by means of scanning electron microscopy after NaOH
      maceration and ultrasonic microdissection of the interstitial connective tissue.
      The muscular wall of the ampulla appears as a continuous network of randomly
      anastomosed smooth muscle cell bundles that showed a multidirectional
      arrangement. The smooth muscle cell bundles modify their orientation along their
      course, intertwine repeatedly with each other and dichotomize, generating new
      bundles with a different orientation from that at the origin. These results
      demonstrate that the myosalpinx of the human ampulla is not organized into clear
      cut longitudinally, circularly or spirally arranged layers, as suggested in
      previous light microscopy studies. In contrast, the presence of a network of
      multidirectional smooth muscle cell bundles revealed in this study suggests that
      there is no morphological evidence for unidirectional peristalsis, and that the
      musculature is probably structurally designed to stir rather than push the tubal
      contents. These morphological findings better explain the random pattern of
      propagation of the contraction waves and the electrical impulses through the
      smooth musculature of the human ampulla, as postulated in early experimental
      physiological studies. Further, they suggest a specific function for the ampullar
      musculature which may not be only strictly related to tubal content transport.

PMID- 8530675
TI  - Comparison among different ovarian stimulation regimens for assisted procreation
      procedures in patients with endometriosis.
AB  - The objective of our study was to establish the most adequate ovarian stimulation
      regimen for assisted procreation in endometriotic patients. It consisted of a
      retrospective analysis comparing the use of the gonadotrophin-releasing hormone
      analogue (GnRHa) buserelin either for 3 months or for 3 weeks and continued with
      ovarian stimulation with human menopausal gonadotrophin (HMG), and the use of
      clomiphene citrate in association with HMG for in-vitro fertilization (IVF) and
      embryo transfer, gamete intra-Fallopian transfer (GIFT) and zygote intra
      Fallopian transfer (ZIFT). A total of 145 patients with endometriosis in 174
      cycles were divided into two groups according to the revised American Fertility
      Society staging of the disease (group A, stages 1 and 2; group B, stages 3 and
      4). The use of GnRHa significantly increased the number of oocytes retrieved.
      GnRH analogues for 3 months gave the highest fertilization rate for groups A and
      B. The cleavage, pregnancy and delivery rates, although higher in the groups
      treated with analogues, did not reach statistical significance. A higher number
      of patients had an embryo transfer in the groups treated with GnRHa (P < 0.05).
      Treatment with GnRHa for either 3 months or for 3 weeks proved to be more
      efficient than clomiphene citrate-HMG for assisted procreation procedures in
      patients with endometriosis.

PMID- 8530676
TI  - Conservative surgery for severe endometriosis: should laparotomy be abandoned
      definitively?
AB  - According to current opinion, surgery at laparotomy for conservative treatment of
      endometriosis is obsolete. The debate on the indications, modalities and results
      of surgical treatment for the most severe forms has recently been rekindled.
      Although some expert endoscopists propose advanced techniques to deal with the
      most problematic pelvic lesions, various authors wonder if such interventions
      have been demonstrated as efficacious and safe enough to justify abandoning the
      standard reference treatment. We have reviewed the data, comments and proposals
      recently published on the topic. The available scientific evidence appears
      insufficient to recommend laparoscopy instead of surgery at laparotomy, even for
      the most severe forms of endometriosis. Intestinal, vesical, periureteral,
      retroperitoneal, and vaginal lesions and large endometriomas associated with
      extensive dense adhesions may still benefit from classical surgery at laparotomy.
      However, the lack of comparative studies prevents a correct comparison of the
      methods in terms of pregnancy rate, resolution of pain and incidence of
      recurrences.

PMID- 8530677
TI  - Effect of peritoneal fluid from infertile women with endometriosis on ionophore
      stimulated acrosome loss.
AB  - The effect of peritoneal fluid (PF) from endometriosis patients was studied in
      spontaneous and stimulus-induced (Ca-ionophore; A23187) acrosome reactions. PF
      samples were obtained from 21 infertile women with endometriosis and five normal
      women (controls). Sperm acrosomes were examined by staining with Pisum sativum
      agglutinin labelled with fluorescein isothiocyanate. The incidence of spontaneous
      acrosome reaction after 1 and 6 h of incubation (6.7 +/- 1.6 and 6.9 +/- 1.4
      respectively) was significantly (P < 0.001) lower when the incubation was
      performed with PF from endometriosis patients in comparison with spermatozoa
      incubated in PF from the control group (12.8 +/- 1.1 and 12.8 +/- 0.8).
      Similarly, the incidence of A23187-induced acrosome reaction after 1 and 6 h of
      incubation (19.8 +/- 2.7 and 20.0 +/- 2.4) was significantly (P < 0.001) lower
      when spermatozoa were incubated with PF from endometriosis patients in comparison
      with spermatozoa incubated with PF from the control group (34.6 +/- 9.8 and 34.4
      +/- 1.1). The incidence of A23187-inducible acrosome reaction was also
      significantly (P < 0.001) lower when the incubation was performed with PF from
      endometriosis patients (13.1 +/- 2.8 and 13.1 +/- 2.4) when compared with that
      from the control group (21.8 +/- 2.6 and 21.6 +/- 1.5). No relationship was found
      between the stage of endometriosis and the incidence of acrosome loss. In
      conclusion, the PF from endometriosis patients decreased both spontaneous and
      stimulus-induced acrosome reaction. This may represent a mechanism for the
      detrimental effect of the PF from endometriosis patients on the spermatozoa
      oocyte interaction and partially explain the aetiology of infertility in patients
      with endometriosis.

PMID- 8530678
TI  - Electrocauterization in rats of experimentally induced endometriosis at a low
      temperature.
AB  - Endometriosis was induced in 40 mature female rats by means of transplantation of
      endometrium on the peritoneum near the ovary. Three weeks later, all the rats
      were laparotomized and they were randomized into four groups according to
      treatment; an untreated group and three groups with electrocauterization at
      different temperatures. Three weeks after these treatments, they were again
      subjected to laparotomy and the implants were examined for their size, histology
      and lactate dehydrogenase (LDH) activity. In the untreated group, the size of the
      implants was increased significantly. Electrocauterization at a high temperature
      (about 300 degrees C) was enough to destroy all the endometriosis and no LDH
      activity was observed. Electrocauterization at a low temperature (70 or 85
      degrees C) with newly developed bipolar forceps also revealed complete remission
      of endometriosis and there was no LDH activity in all the transplantation sites
      examined. These results indicate that the electrocauterization of endometriosis
      at a low temperature is safe and as effective as that at a high temperature.

PMID- 8530679
TI  - Embryo score to predict implantation after in-vitro fertilization: based on 957
      single embryo transfers.
AB  - The purpose of this study was to devise an embryo score to predict the likelihood
      of successful implantation after in-vitro fertilization (IVF). Unlike most
      studies dealing with the influence of embryo stage and morphology on pregnancy,
      our study was based on single rather than multiple embryo transfers. A total of
      957 single embryo transfers were carried out. No delivery was obtained after any
      of the 99 transfers using 1-cell embryos or embryos obtained after delayed
      fertilization. In the remaining 858 transfers, the embryos had cleaved. Higher
      pregnancy rates were obtained with embryos displaying no irregular cells (11.7
      versus 6.9%; P < 0.01) and embryos displaying no fragmentation (11.5 versus 8.1%;
      P < 0.05). The 4-cell embryos implanted 2-fold more often than embryos with more
      or less cells (15.6 versus 7.4%; P < 0.01). Based on these observations, we
      devised a 4-point embryo score in which embryos are assigned 1 point each if they
      (i) are cleaved, (ii) present no fragmentation, (iii) display no irregularities,
      and (iv) have four cells. Both pregnancy rate and take home baby rate were
      significantly correlated with embryo score. Each point of this score corresponds
      to a 4% increase in pregnancy rate. Interestingly, pregnancy rate was
      significantly lower in women aged > 38 years (8.2 versus 11.4%; P < 0.05), even
      though embryo quality was similar regardless of age. Single embryo transfer
      allowed us to define a simple and useful embryo score to choose the best embryo
      for transfer to optimize IVF and embryo transfer outcome. The use of this embryo
      score could decrease multiple pregnancies after multiple embryo transfers.

PMID- 8530680
TI  - Clinical evidence for a detrimental effect on uterine receptivity of high serum
      oestradiol concentrations in high and normal responder patients.
AB  - This study was undertaken to investigate an empirical observation that 'high
      responder patients have poorer in-vitro fertilization (IVF) outcome than normal
      responder patients'. The aim of our study was to analyse the effect of high serum
      oestradiol and progesterone concentrations at the day of human chorionic
      gonadotrophin (HCG) administration on endometrial receptivity and oocyte-embryo
      quality in high and normal responder patients. The IVF patients were divided into
      two groups: 59 high responder patients who voluntarily donated some of their
      oocytes, and a control group consisting of 105 normal responder patients. Both
      groups were compared in terms of the number and quality of oocytes retrieved,
      embryos transferred, fertilization, implantation and gestation rates, serum
      oestradiol and progesterone concentrations and the oestradiol:progesterone ratio
      on the day of HCG injection. To ascertain oocyte-embryo quality, a second control
      group of 96 women undergoing oocyte donation (receiving oocytes from high
      responder patients) was considered. To assess the impact of steroid
      concentrations on endometrial receptivity, high responder patients were divided
      into two subgroups according to oestradiol concentration, above or below the
      minimal oestradiol and progesterone concentrations (mean--SD) in this group. The
      normal responder patients were divided into two subgroups according to oestradiol
      concentration, above or below the maximal oestradiol and progesterone
      concentrations (mean+SD) in this group. To assess further the relevance of
      oestradiol concentration on endometrial receptivity, patients were divided into
      different subgroups according to increasing oestradiol concentration, regardless
      of whether they were high or normal responders. High responder patients had
      significantly decreased implantation and pregnancy rates per cycle compared with
      normal responder patients (33.3 versus 16.3 and 11.1 versus 5.4% respectively; P
      < 0.05). The results of 108 embryo transfers in 91 recipients who received
      oocytes from the high responder group showed normal embryo quality. Implantation
      rates and pregnancies per cycle were significantly lower in high responder
      patients with serum oestradiol concentrations > 1700 pg/ml compared with those
      having oestradiol concentrations < or = 1700 pg/ml, as well as in normal
      responder patients with serum oestradiol concentrations > 2200 pg/ml compared
      with those having oestradiol concentrations < or = 2200 pg/ml. Considering all
      the patients together, significant decreases in pregnancy and implantation rates
      were observed when oestradiol concentrations were > 2500 pg/ml compared with
      patients having lower oestradiol concentrations. Our clinical results demonstrate
      that high serum oestradiol concentrations on the day of HCG injection in high and
      normal responder patients, regardless of the number of oocytes retrieved and the
      serum progesterone concentration, are detrimental to uterine receptivity without
      affecting embryo quality.

PMID- 8530681
TI  - Abnormal amniotic fetal antigen 2 concentrations in trisomy 18 and trisomy 21.
AB  - Fetal antigen 2 (FA-2) is a human protein, first identified in amniotic fluid,
      and shown to be identical to the aminopropeptide of the alpha 1 chain of collagen
      type I. It exists in several different size and charge forms. In the present
      study, FA-2 was measured in amniotic fluid using two different assays: a rocket
      line immunoelectrophoretic assay which measured total FA-2, and a
      radioimmunoassay which was specific for the high molecular mass forms of FA-2.
      Both assays gave similar results. FA-2 concentrations were measured in amniotic
      fluid samples collected from normal pregnancies at 10-23 weeks gestation; they
      were shown to rise steeply from 10-14 weeks, peak at 17 weeks and then fall
      slightly by 23 weeks. Comparison between amniotic fluid from normal pregnancies
      and pregnancies affected by trisomy, showed significantly higher FA-2
      concentrations in trisomy 21 and significantly lower concentrations in trisomy
      18.

PMID- 8530682
TI  - Proliferative activity in ectopic trophoblastic tissue.
AB  - Clinical observations have shown that tubal pregnancies develop individually
      different biological activities such as different growth rates, levels of beta
      human chorionic gonadotrophin (beta-HCG), or rates of tubal wall destruction. In
      the present study, we evaluated the proliferative activity of ectopic
      cytotrophoblastic tissue using immunocytochemistry with antibodies to Ki-67
      (clone MIB-1). The rates of proliferation obtained were related to the maternal
      serum beta-HCG values. Reference data were obtained from placentas of intact
      intrauterine pregnancies (group I, n = 14). The proliferative activity of this
      tissue was compared to that of cytotrophoblastic tissue of tubal pregnancies
      (group II, n = 27). Ki-67-immunostained as well as non-stained cytotrophoblastic
      nuclei of the villi and the trophoblastic columns were counted separately, and
      results were expressed as percentage of positive cells. Serum beta-HCG values
      were determined twice, 48 h and immediately before operation. The
      cytotrophoblastic cells of intact intrauterine pregnancies (group I) showed
      uniform and high proliferative activities (80% on average in villi, 84% on
      average in columns). The average Ki-67 proliferation rate was significantly lower
      (P < 0.001) in trophoblastic tissue of tubal pregnancies (group II; 42% on
      average in villi, 61% on average in columns). Within the group of tubal
      pregnancies, higher intragroup differences were observed. The number of Ki-67
      labelled cells was independent of the absolute preoperative serum beta-HCG values
      in both groups, yet they were clearly related to the relative increase of beta
      HCG in maternal serum. At higher proliferation rates, there was a significant,
      growing increase of beta-HCG values (P < 0.01). We have found immunohistochemical
      evidence to support the previous clinical speculations that tubal pregnancies
      develop more heterogeneously and more slowly than intact intrauterine
      pregnancies. The development of the beta-HCG concentrations may be taken as an
      indirect parameter, reflecting proliferative activity of the trophoblast.

PMID- 8530683
TI  - Placental isoferritin patterns during normal first trimester and tubal
      gestations.
AB  - Placental isoferritin (PLF) has been shown to be involved in the down-regulation
      of the maternal immune system during pregnancy. In a prospective study, serum PLF
      concentrations were measured in 33 pregnant women with singleton, normal, ongoing
      first trimester gestations and compared with those of 22 women with tubal
      gestations. Diagnoses were based on endocrinological, sonographic, intra
      operative and histopathological criteria. Venous blood was obtained from both
      groups for PLF determination before evacuation of the pregnancy products. beta
      Human chorionic gonadotrophin (HCG), 17 beta-oestradiol and progesterone were
      determined at surgery for the tubal pregnancy patients. The mean +/- SD PLF
      concentrations were 18 +/- 14, 25.4 +/- 42.3 IU/ml among normal and tubal
      gestations respectively. Significant differences between normal and tubal
      pregnancies were found (P < 0.05). Based on PLF measurements, sensitivity (67%)
      and specificity (33%) values were found to be similar for the normal and ectopic
      pregnancies. No correlation was found between the other measured pregnancy
      hormones and PLF for the tubal pregnancy group. Low PLF concentrations among
      pathological gestations may reflect abnormal trophoblastic activity. The
      simultaneous assessment of PLF and beta-HCG concentrations which probably
      originate from different trophoblastic cells, is recommended for better diagnosis
      and monitoring of first trimester placental activity.

PMID- 8530684
TI  - Ultrasonographic features of uterine blood flow during the first 16 weeks of
      pregnancy.
AB  - Uterine blood flow volume has been thought to increase in a linear fashion
      throughout pregnancy, but previous studies in early pregnancy may have not been
      performed often enough or in sufficient numbers of patients. We measured uterine
      artery blood flow volume, average velocity, vessel cross-sectional area,
      resistance index, and spiral artery resistance index with Doppler ultrasound at 1
      3 week intervals from gestational (post-menstrual) weeks 5-6 to week 16 in 44
      normal, spontaneous, single pregnancies. Uterine artery blood flow volume and
      velocity increased gradually until the end of week 9, and then rapidly from weeks
      10-16. Uterine artery vessel size increased linearly. The uterine artery
      resistance index was the inverse of volume and velocity, in contrast to the
      spiral artery resistance index, which decreased linearly. These findings indicate
      that early pregnancy changes in uterine and spiral artery blood flow occur by
      different mechanisms, and that when investigating uterine blood flow in early
      pregnancy, studies need to begin by week 6 and need to be performed at least
      biweekly.

PMID- 8530685
TI  - Changes in the coelomic fluid composition following two different methods of
      cervical ripening.
AB  - We have evaluated the changes in maternal serum and coelomic fluid biochemical
      composition following two different methods of cervical ripening, i.e. mechanical
      and biochemical. Each study group included 20 women between 8 and 12 weeks of
      gestation who were requesting termination for psychosocial reasons. In the first
      group, a 3 mm hypan (synthetic hygroscopic dilator) was inserted into the cervix
      12 h preoperatively. In the second group, two 1 mg pessaries of gemeprost
      (prostaglandin analogue) were inserted into the posterior fornix 6 and 2 h
      preoperatively. Coelomic fluid and maternal serum were obtained at the time of
      the surgical procedure and assayed for urea, total protein, potassium, sodium,
      human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP). Significantly
      higher coelomic fluid sodium (t = 4.72; P = 0.029) and significantly higher
      maternal serum AFP (t = 13.21; P < 0.001) concentrations were observed after
      gemeprost than after hypan. There was no difference in the concentration of
      potassium, urea, total protein and HCG between the two groups. These findings
      indicate that prostaglandin analogues, when used for cervical ripening, provoke a
      breakdown of the placental barrier resulting in an increase in AFP molecules
      transferred from the fetal fluid compartments into the maternal circulation. The
      results also suggest that these drugs increase the placental permeability to
      sodium with a secondary accumulation of this ion in the coelomic fluid.

PMID- 8530686
TI  - Induction of artificial endometrial cycles with oestradiol implants and
      injectable progesterone: establishment of a viable pregnancy in a woman with 17
      alpha-hydroxylase deficiency.
AB  - Repeated attempts with oral oestrogens and injectable progesterone failed to
      induce secretory endometrium in a woman with 17-alpha-hydroxylase deficiency. The
      insertion of s.c. 17-beta-oestradiol implants dramatically improved the
      endometrial response and enabled the establishment of endometrial maturation. A
      viable pregnancy was achieved after the uterine transfer of in-vitro fertilized
      donated eggs.

PMID- 8530687
TI  - Partial hydatidiform mole and hypertension associated with a live fetus--variable
      presentation in two cases.
AB  - Partial hydatidiform mole associated with live births is a rare condition. There
      are not enough cases in the literature to allow the assessment of comprehensive
      risks to be made and upon which management policies can be based. Several
      clinical dilemmas arise following diagnosis of a viable pregnancy associated with
      molar tissue. We present two cases demonstrating the problems and suggest
      management based on outcome and a review of the literature.

PMID- 8530688
TI  - A case of severe diabetic retinopathy in pregnancy.
AB  - Proliferative retinopathy is a recognized long-term complication of diabetes and
      the commonest cause of blindness in young people. There is, however, some
      uncertainty regarding counselling given on the continuation of pregnancy when it
      is complicated by retinopathy. This case is used to highlight this difficulty and
      to discuss management based on literature review.

PMID- 8530689
TI  - Clomiphene citrate, gonadotrophin and sex ratio of offspring.

PMID- 8530690
TI  - Infant sex ratio after hormonal ovulation induction.

PMID- 8530691
TI  - Primers for mice sex determination.

PMID- 8530692
TI  - Composition of the human zona pellucida and modifications following
      fertilization.
AB  - The composition of individual human zonae pellucidae and modifications to this
      extracellular coat both before and after fertilization were analysed using a
      rapid, sensitive, non-radioactive biotinylation- or lectin-based detection
      system; these assays use commercially available reagents and can be performed on
      fragments of individual zonae pellucidae. The zona pellucida from unfertilized
      eggs is composed of three glycoprotein species designated as huZP1, huZP2 and
      huZP3. Under non-reducing conditions, the molecular weights of these proteins are
      approximately 150 kDa, approximately 100 kDa, and approximately 55-65 kDa
      respectively. Following fertilization, huZP1 was not detected under either non
      reducing or reducing conditions. In contrast, after fertilization huZP2 was
      detected under non-reducing conditions, but not under reducing conditions. The
      ability to detect pre- and post-fertilization changes in a single human zona
      pellucida is discussed in relation to its value in assessing deficiencies in
      clinical and laboratory protocols used for in-vitro fertilization.

PMID- 8530693
TI  - Immunohistochemical localization, identification and regulation of the
      interleukin-1 receptor antagonist in the human endometrium.
AB  - There is evidence suggesting the importance of the interleukin-1 receptor type I
      (IL-1Rtl) and interleukin-1 beta (IL-1 beta) as mediator in local intercellular
      interactions in endometrial tissue and embryonic implantation. To complete our
      understanding of the entire endometrial IL-1 system in humans, we have
      investigated the immunohistochemical distribution of IL-1 receptor antagonist (IL
      1ra) in the human endometrium throughout the menstrual cycle. We have also
      identified the forms of IL-1ra present in human endometrial cells. Immunoreactive
      IL-1ra was found in both cryostat and paraffin-embedded sections of human
      endometrium using the alkaline phosphatase-peroxidase (A-P) method with two
      different IL-1ra antibodies. IL-1ra was present throughout the entire menstrual
      cycle, located primarily in the endometrial epithelium. However, IL-1ra staining
      was significantly higher during follicular phase in comparison with early and mid
      late luteal phases. Reverse transcriptase polymerase chain reaction of cultured
      stromal and glandular cells showed that these cells express the intracellular
      form of IL-1ra mRNA (icIL-1ra). Our results demonstrate the regulated presence of
      the icIL-1ra in the human endometrium. This finding supports a possible autocrine
      paracrine role for the IL-1 system in the human endometrium and embryonic
      implantation.

PMID- 8530694
TI  - Urinary vascular endothelial growth factor concentrations in women undergoing
      gonadotrophin treatment.
AB  - A recently identified cytokine, vascular endothelial growth factor (VEGF,
      vascular permeability factor) has been implicated in ovarian hyperstimulation
      syndrome in women undergoing assisted reproduction. We postulate that circulating
      and urinary VEGF values increase following gonadotrophin stimulation, in parallel
      with the increased ovarian vascularity. A VEGF radioimmunoassay was developed
      using iodinated VEGF as tracer, a goat anti-VEGF serum as antiserum and
      recombinant human VEGF as standard. The specificity of the assay was confirmed by
      comparing the reverse phase high-performance liquid chromatography (HPLC) pattern
      of VEGF immunoactivity in urine and urine spiked with recombinant VEGF. Urine was
      concentrated 5-fold prior to measurement by the radioimmunoassay. VEGF:creatinine
      ratios in early morning urine samples were used to monitor daily urinary VEGF
      concentrations based on its high correlation (r = 0.77, P < 0.001) with VEGF
      concentrations in 24 h urine collections. No diurnal variation in VEGF:creatinine
      ratios was detected. VEGF:creatinine ratios were determined daily from nine women
      undergoing gonadotrophin-releasing hormone (GnRH) agonist/gonadotrophin
      treatment. In a further 16 women, early morning urine samples were collected in
      the peri-ovulatory period. A significant increase (P < 0.005, n = 25) was
      observed in VEGF:creatinine ratios following human chorionic gonadotrophin (HCG)
      administration. VEGF:creatinine ratios correlated poorly (r < 0.34) with plasma
      oestradiol, follicle number and size. It is concluded that urinary
      VEGF/creatinine ratios increase following HCG stimulation.

PMID- 8530695
TI  - In-vitro endometrial secretion of human interleukin for DA cells/leukaemia
      inhibitory factor by explant cultures from fertile and infertile women.
AB  - Human interleukin for DA cells/leukaemia inhibitory factor (HILDA/LIF) is a
      cytokine with pleiotropic effects involved in successful murine implantation. We
      evaluated human uterine HILDA/LIF production by monitoring its in-vitro secretion
      by endometrial explant cultures obtained from individuals in either normal or
      pathological conditions. The cytokine secretion was standardized using the day
      5:day 1 ratio of HILDA/LIF concentration in supernatants of such cultures, hereby
      termed HILDA/LIF production index (HLPI). Our results confirmed that HILDA/LIF is
      secreted by the human endometrium as assessed by secretion at every phase of the
      cycle in either normal fertile women, or women bearing intrauterine devices. This
      was also the case for samples obtained from infertile women presenting repeated
      failures of embryonic implantation or unexplained primary sterility. However, the
      HLPI were significantly lower in those latter two groups when compared to fertile
      women. These results suggest an abnormal regulation of HILDA/LIF secretion in
      such circumstances, and the clinical implication of those data is discussed.

PMID- 8530697
TI  - Association between mannan binding protein deficiency and recurrent miscarriage.
AB  - The distribution of mannan binding protein (MBP) in blood donor sera was
      determined by enzyme-linked immunosorbent assay to establish normal
      concentrations. Abnormally low MBP concentrations were found in 16% (21 out of
      135) of female partners and 14% (15 out of 108) of male partners of couples
      experiencing recurrent miscarriage, compared with < 5% of obstetrically normal
      controls (P < 0.005). This relationship was even stronger (9.5 versus 1.0%) and
      more significant (P < 0.002) when only subjects presumed to be homozygous for the
      mutant allele responsible for MBP deficiency were considered. By
      immunohistochemistry, MBP could be demonstrated in first trimester placenta. We
      suggest that low concentrations of MBP within the feto-placental unit increase
      susceptibility to fetal loss, possibly via an infection-induced placental
      cytokine imbalance.

PMID- 8530696
TI  - Human trophoblast adhesion to matrix proteins: inhibition and signal
      transduction.
AB  - At the time of implantation, the extracellular matrix proteins laminin and
      fibronectin are abundant in the decidua and are distributed pericellularly around
      each individual stromal cell. First trimester human trophoblast expresses both
      laminin and fibronectin receptors, specifically the alpha 1 beta 1, alpha 5 beta
      1, alpha 6 beta 1 and alpha 6 beta 4 integrin heterodimers. In this study we have
      demonstrated that in-vitro adhesion of first trimester human trophoblast to
      purified extracellular matrix proteins and to purified decidual stromal cell
      monolayers can be inhibited by monoclonal antibodies directed against appropriate
      integrin subunits and by synthetic peptides containing an arginine-glycine
      aspartic acid sequence. Monoclonal antibodies (mAbs) to the alpha 5 and beta 1
      integrin subunits and a synthetic peptide significantly inhibited adhesion to
      fibronectin. Binding of trophoblast to laminin was blocked with mAbs to the alpha
      6 and beta 1 but not alpha 1 and beta 4 integrin subunits. Similarly, integrin
      mediated adhesion to monolayers of decidual stromal cells could be blocked with
      mAbs to the alpha 5, alpha 6, beta 1 and beta 4 integrin subunits. Integrin
      mediated signal transduction in normal and malignant trophoblast was investigated
      by Western blotting. A 115 kDa protein was the major tyrosine phosphorylated
      protein detected in trophoblast after binding to laminin or fibronectin. The
      profile of tyrosine phosphorylated proteins differed for malignant trophoblast.

PMID- 8530698
TI  - Placental expression of alpha and beta subunits of human chorionic gonadotrophin
      in early pregnancies with Down's syndrome.
AB  - This study examines the expression of alpha and beta subunits of human chorionic
      gonadotrophin (HCG) in samples of placental and decidual tissue obtained at 11-15
      weeks of gestation from 30 control pregnancies and 11 pregnancies with trisomy
      21. In the placental tissue, the concentrations of beta-HCG mRNA and alpha-HCG
      mRNA were augmented in six and seven of the trisomy 21 cases respectively and in
      16 and 14 of the control pregnancies. The median values of beta-HCG mRNA and
      alpha-HCG mRNA in the two groups were not significantly different. Although the
      median serum free beta-HCG concentration was significantly (P = 0.03) higher in
      trisomy 21 pregnancies than the controls, there was no relationship between serum
      free beta-HCG and relative abundance of beta-HCG mRNA in either the trisomy 21
      pregnancies or the controls. Decidual expression of beta-HCG and alpha-HCG mRNA
      were below detection level in the Northern blot analysis in both the trisomy 21
      pregnancies and the controls. These findings suggest that the increase in
      maternal serum free beta-HCG concentration in trisomy 21 pregnancies occurs
      during the post-transcriptional phase of HCG protein biosynthesis.

PMID- 8530699
TI  - Nucleated erythrocytes in maternal blood: quantity and quality of fetal cells in
      enriched populations.
AB  - The discovery of nucleated erythrocytes in maternal circulation provides a
      potential source for non-invasive prenatal diagnosis. We have evaluated the use
      of a three-stage procedure to determine the number of cells that are of fetal
      rather than maternal origin. First, monoclonal antibodies specific for CD45 and
      CD14 were used in conjunction with a magnetic (MACS) column to deplete unwanted
      leukocytes from maternal blood. This was followed by a positive MACS enrichment
      for nucleated erythrocytes, using an anti-CD71 (transferrin receptor) monoclonal
      antibody. To discriminate between fetal nucleated erythrocytes and those of
      maternal origin, enriched fractions were simultaneously stained with an anti
      fetal haemoglobin (HbF) antibody and hybridized with probes specific for X and Y
      chromosomes. Samples were then subjected to blind analysis along with negative
      control samples from non-pregnant volunteers. Using this dual analysis, we were
      able to determine that less than one nucleated erythrocyte per ml of maternal
      blood was of fetal origin. Small numbers of these fetal cells were found in 87.5%
      of pregnancies, ranging from 6 to 35 weeks gestational age. Comparison of HbF and
      X/Y probe data also suggests that the fetal cells are less suitable for
      fluorescence in-situ hybridization (FISH) analysis than similar preparations from
      other sources.

PMID- 8530700
TI  - Virtual image guided navigation in tumor surgery--technical innovation.
AB  - We present a new visualization system for image-guided stereotactic navigation in
      tumor surgery. The combination of frameless stereotactic localization technology
      with real-time video processing permits the visualization of medical imaging data
      as a video overlay during the actual surgical procedure. Virtual computer
      generated anatomical structures are displayed intraoperatively in a semi
      immersive head-up display. This results in surgical navigation assistance without
      limiting the judgement of the physician based on the continuous observation of
      the operating field. The case presented documents the potential of augmented
      reality visualization concepts in tumor surgery of the head.

PMID- 8530701
TI  - Hemifacial hypoplasia and hypomelanosis of Ito.
AB  - We present three cases of hemifacial hypoplasia associated with hypomelanosis of
      Ito. The facial deformity is often severe with marked soft tissue shortage and
      underlying skeletal hypoplasia posing difficulty in reconstruction. The external
      ear is relatively uninvolved, although a degree of hypoplasia is usually present.
      The hallmark of hypomelanosis of Ito is linear depigmentation of skin often
      associated with asymmetric abnormalities. It is a heterogenous disorder due to
      chromosomal mosaicism, but cytogenetic confirmation of the diagnosis may be
      difficult. The relationship between mosaicism and anatomical asymmetry is
      discussed.

PMID- 8530702
TI  - A computerized non-invasive method for the assessment of human facial volume.
AB  - The three-dimensional coordinates of 22 standardized soft-tissue facial landmarks
      were used in the definition of a three-dimensional model of the adult human face.
      The model allows the estimation of the volume of the face in toto and of its
      parts (upper, middle and lower thirds, nose). Landmark coordinates were collected
      in 80 healthy young adults (40 men and 40 women selected according to criteria of
      dentofacial normality) by infrared photogrammetry by an automated instrument, and
      facial volumes calculated. Sample variability was larger in women than in men;
      the nose and the upper third of face had the largest variability regardless of
      gender. On average, all volumes computed in men were significantly larger than
      the corresponding values computed in women. Also the lower-to-middle third face
      ratio was significantly higher in men than in women. The sexual dimorphism in
      human facial volume did not involve the different parts of the face to the same
      extent: a large part of male facial volume preponderance was explained by the
      lower third of face. The proposed facial model could adequately represent the
      human face in all those research and clinical fields where noninvasive surface
      measurements could be employed alone or in support of conventional radiographic
      data.

PMID- 8530703
TI  - Stability of simultaneous modified LeFort III/LeFort I osteotomies.
AB  - The objective of this study was to examine maxillary skeletal stability after
      simultaneous modified LeFort III/LeFort I osteotomy in patients who presented for
      the simultaneous correction of midface and maxillary hypoplasia. Eleven patients
      underwent simultaneous modified LeFort III/LeFort I osteotomies using transoral
      and transconjunctival surgical approaches. The mean net surgical movement at A
      point (A pt) was 5.2 mm anteriorly and 2 mm inferiorly. Titanium mini-plates were
      used to stabilize both the midface component and the LeFort I segment; iliac
      crest or calvarial bone grafts as well as freeze-dried cancellous blocks were
      used at the zygoma and lateral orbital rim regions. All patients had lateral
      cephalometric radiographs taken immediately postoperatively, and at their sixth
      week, sixth month, and one year follow-up visits. Five maxillary landmarks (CI, A
      pt, ANS, PNS, and 2M) were used to examine the horizontal and vertical changes
      occurring at each time period. The central incisor relapsed vertically 2.8 mm at
      six months, A pt relapsed vertically 2.3 mm at six months, ANS relapsed
      posteriorly 1.6 mm at 6 weeks, PNS relapsed 1.5 mm anteriorly at one year. This
      study demonstrated that the maxilla moved anteriorly 1.5 mm and superiorly 2.8 mm
      in simultaneous modified LeFort III/LeFort I osteotomies performed with mini
      plate fixation and bone grafts. This movement should be considered when planning
      and performing simultaneous surgical movement of the maxilla and midface using
      modified LeFort II/LeFort I osteotomies. Appropriate occlusal overcorrection at
      the time of surgery is necessary.

PMID- 8530704
TI  - New findings concerning early bone grafting procedures in patients with cleft lip
      and palate.
AB  - The following paper reports on our investigations of long-term results of 177
      primary bone grafting procedures carried out in the period from 1959 to 1969. In
      an assessment of possible influential factors (multivariate statistical
      analysis), neither age at operation, dental hygiene, cleft form, aplasia or loss
      of teeth near cleft nor the surgeon was found to influence the success of the
      primary bone grafting procedure. The only significant correlation we found was
      that between cleft width and Bergland Index. In small clefts up to 4 mm wide,
      Bergland Index IV was not recognized. However, no cleft larger than 8 mm
      developed a Bergland Index I. Our results lead to the conclusion that primary
      bone grafting in wide clefts should not be performed as a single-stage procedure.
      We presume that, in wide clefts, a two-stage primary bone grafting procedure
      would likely have led to better long-term results.

PMID- 8530705
TI  - Cranial dislocation of the mandibular condyle. A case report with an unusual
      hearing loss.
AB  - The case of a 37-year-old woman who suffered a condylar dislocation into the
      middle cranial fossa is reported. The mechanisms of injury, the problems of
      clinical diagnosis and the management are discussed.

PMID- 8530707
TI  - Retained pieces of wood in the retromaxillary space: a case report.
AB  - Detection and operative removal of wood as a foreign body in the cranio-maxillary
      area has received frequent attention in the literature. However, as a rule, most
      of the cases described are related to the orbit or the orbito-neurocranial space.
      Almost no literature exists on the detection and treatment of wooden foreign
      bodies in the retromaxillary space. The authors present an unusual case of long
      term retained wood in this area in a child. The case inspires discussion of the
      general problem of detecting retained retromaxillary wood, even using modern
      diagnostic tools in this area and the question of the operative therapy,
      especially the most favourable surgical access.

PMID- 8530706
TI  - Experimental evaluation and clinical use in the head and neck of a 3M/Precise
      microvascular anastomotic device.
AB  - Microvascular reconstructions in the head and neck are usually long operating
      time procedures. Mechanical anastomotic devices help to reduce operating time and
      can reduce anastomotic failures avoiding foreign bodies in the lumen of the
      vessel. One of these systems is the 3M/Precise microvascular anastomotic device,
      it is a non-absorbable device, however, criticisms of this system have been
      directed to the fact that pulsation of the vessel wall against a rigid structure
      could lead to thinning of the vessel wall and aneurysm formation. No aneurysms
      have been found previously in other experimental models. Our experimental study
      on the aorta and vena cava of the rat comprises 25 arterial and 25 venous
      anastomoses. In the arteries, four proximal aneurysms were found, two of these
      were failures. In the venous anastomoses, no failures were found nor aneurysm
      formation. The system is very useful for performing clinical end to end venous
      anastomosis helping to reduce anastomotic failures. Aneurysms have been found in
      arteries although four different ring sizes were available. The device is less
      easy to use in them than in veins and sometimes can be difficult to apply, making
      manual suturing a better choice for clinical arterial anastomosis.

PMID- 8530708
TI  - Intra-operative scalp expansion for wound closure without tension in
      craniosynostosis operation--technical innovation.
AB  - Primary scalp wound closure using intra-operative scalp expansion in a
      craniosynostosis operation is described. Since this method enables easy scalp
      expansion, it is considered to be a useful adjunctive technique which should be
      taken into account when closing scalp wounds in craniosynostosis surgery, where
      the risk exists of cranial expansion-induced compression and deformity of the
      remodelled bone flaps after bone fixation.

PMID- 8530709
TI  - Stabilization of the short sagittal split osteotomy: in vitro testing of
      different plate and screw configurations.
AB  - Using a 3-dimensional in vitro model, the stability of different types of
      osteosynthesis for the short sagittal osteotomy was tested. The following four
      groups of plate and screw configurations were evaluated: Group I: Fixation with
      miniplates using monocortical screws only, Group II: Fixation with miniplates,
      but with two of the screws engaging both fragments, Group III: Same as group II
      with an additional position screw, Group IV: Fixation with 3 position screws. The
      stability obtained with miniplate fixation using monocortical screws only (group
      I) was by a factor of 2.9 less than position screw fixation (group IV), which is
      considered to be an approved standard. In order to increase the stability of
      miniplate fixation, the screws in the area of overlapping bone should engage both
      fragments.

PMID- 8530710
TI  - Recovery of infraorbital nerve function after zygomaticomaxillary cheek pedicled
      flap.
AB  - The zygomaticomaxillary cheek pedicled flap (ZMCF) involves the intentional
      section of the infraorbital nerve to reflect the flap laterally in order to give
      access to the rhinopharynx, clivus and upper cervical spine. The aim of this
      trial was to examine the recovery of sensation of the infraorbital nerve, both
      quantitatively (touch sensation, localisation test, two-point discrimination) and
      qualitatively (sharp/blunt test, temperature sensation, pain sensitivity, dental
      sensitivity) in 7 patients, at least 12 months after surgery. In each patient,
      four cutaneous areas (lower eyelid, nose ala, upper lip, cheek) and the upper
      vestibulum were tested. Results of each test in all the examined areas were
      evaluated and compared with the data obtained on the nonoperated side (control
      side). Results of neurosensory tests indicated good recovery of sensation with
      little difference in comparison with the control side, showing that the
      functional consequence of ZMCF should actually be considered only as a transitory
      event.

PMID- 8530711
TI  - Surgical techniques in orbital roof fractures: early treatment and results.

PMID- 8530712
TI  - Benefit/risk of estrogen therapy in cardiovascular disease: current knowledge and
      future challenges.
AB  - In the United States, cardiovascular disease represents the leading cause of
      death among women. A majority of the deaths are due to coronary disease. In
      addition, the incidence of heart attacks increases with age. Among those who are
      65 years of age or older, the estimated heart attack rate is 374,000 per year for
      women, compared with 440,000 per year for men. In the past three decades, a
      number of observational studies have suggested that estrogen therapy can reduce
      the risk of coronary disease in postmenopausal women. This protective effect
      appears to be much greater in women who have existing coronary disease. These
      observational data point to the potential usefulness of estrogen therapy in
      preventing cardiovascular death among women. Although large, well-controlled,
      clinical trials are needed to confirm the benefit of estrogen therapy, several
      important findings strongly support the cardioprotective effect of estrogen
      therapy. For example, in monkeys estrogen prevents the accumulation of low
      density lipoprotein (LDL) cholesterol (a known risk factor for heart disease) in
      coronary arteries, and estrogen has also been shown to increase high-density
      lipoprotein (HDL) cholesterol (a known cardioprotective factor). Estrogen also
      possesses a vasodilating property, which can improve cardiac performance in
      ischemic heart disease. In addition, recent studies have demonstrated that
      estrogens (especially equilin) exhibit a high antioxidant effect, which may also
      be related to cardioprotectivity. Although estrogen therapy has been observed to
      decrease the risk of coronary disease, long-term estrogen therapy has also been
      found to increase the risk of uterine carcinoma; the addition of progesterone to
      estrogen therapy may lessen this undesirable risk, however. On the other hand the
      addition of progesterone to estrogen therapy may decrease estrogen's beneficial
      effect on HDL cholesterol. What should be the present position on estrogen
      therapy in postmenopausal women? What is the best dosage regimen? Should it be
      used alone or in combination with a progesterone? These important issues are
      discussed, as are several current clinical trials addressing the issue of
      estrogen therapy in postmenopausal women.

PMID- 8530713
TI  - Pharmacokinetic and pharmacologic variation between different estrogen products.
AB  - Due to the complex nature of endogenous and exogenous hormone concentration,
      formation, and metabolism and assay complexity, the pharmacokinetics of estrogen
      are difficult to study. Oral estrogens have minimal systemic bioavailability (2%
      to 10%) due to gut and liver (first-pass) metabolism. High concentrations of
      estrone are achieved with oral administration, whereas higher concentrations of
      estradiol are generally achieved after percutaneous absorption. Although vaginal
      products (such as gel, rings, etc.) are administered locally, they achieve high
      serum concentrations. Estradiol and estrone concentrations and estradiol-to
      estrone ratios vary with different estrogen therapies. Approximately 95% to 98%
      of estradiol is bound loosely to albumin or tightly to sex hormone binding
      globulin, the major binding protein. The terminal half lives for the different
      estrogen compounds (after oral or intravenous administration) vary from 1-12
      hours. Some conversion rates have been calculated between estrogen and its
      metabolites. Smoking decreases achievable estrogen concentrations, and has a
      greater effect on oral products. Oral contraceptives have been found to decrease
      antipyrine clearance. In the one study evaluating conjugated estrogens,
      antipyrine clearance was not altered. Oral contraceptives have a variable effect
      on the elimination of medications. Acetaminophen clearance is increased, whereas
      clearance of some benzodiazepines, caffeine,and prednisolone is decreased.
      Phenytoin increases the metabolism of conjugated estrogens. The various estrogen
      products may produce different clinical effects based on composition. The
      metabolites (minor components) of conjugated estrogens have been found to have
      significant effects on lipid concentrations, uterine weight, liver generated
      compounds, and bone resorption. Because transdermal products bypass the first
      pass effect, delayed or decreased effects on lipid profiles and liver generated
      compounds have been observed.

PMID- 8530714
TI  - Estrogen therapy for postmenopausal symptoms and prevention of osteoporosis.
AB  - Menopausal symptoms are noted as estrogen deficiency affects target tissues
      during the climacteric and after menopause. With estrogen replacement therapy
      (ERT), clinical signs, such as vasomotor symptoms and genitourinary atrophy,
      abate. Estrogen replacement therapy protects against the development of
      osteoporosis and is used in its treatment. In addition, ERT has a positive effect
      on serum lipids and appears to be protective against coronary heart disease. More
      than 75% of all women experience troublesome vasomotor symptoms during the
      climacteric years, and osteoporosis is a major cause of morbidity and mortality
      in postmenopausal women. In the United States, the current annual cost of
      treating patients with osteoporosis is $10 billion dollars. With the aging of the
      baby boom generation, it is estimated that osteoporosis-associated costs may
      double in the next 30 years if interventions are not undertaken to reduce the
      incidence of osteoporosis. It is therefore important for pharmacists and other
      health care practitioners to educate women about ERT after menopause to reduce
      the risks of vasomotor symptoms, osteoporosis, and other problems. The incidence,
      etiology, symptoms, and therapeutic measures used to reduce vasomotor symptoms
      are discussed, and updates on pathophysiology, risk factors, prevention, and
      treatment of osteoporosis, with an emphasis on ERT, are reviewed.

PMID- 8530715
TI  - Future therapeutic developments of estrogen use.
AB  - The potential long-term benefits of estrogen replacement therapy (ERT) in the
      prevention of osteoporosis and heart disease have been reasonably well
      established. However, the favorable effects of ERT on cognitive function and
      prevention of senile dementia in old age now represents a revitalized area of
      clinical research. A growing body of experimental evidence has recently provided
      the neurobiologic basis to support the hypothesis that gonadal hormones such as
      estrogen have psychologic effects on human brain function and behavior. Studies
      in women who have undergone surgical menopause have demonstrated that the
      menopause is associated with subclinical cognitive and affective dysfunction,
      which is improved by ERT. In addition, a growing body of evidence suggests that
      estrogen may be an effective therapy for senile dementia in some elderly women.
      Recent epidemiologic studies have indicated that long-term postmenopausal ERT may
      prevent late-life cognitive dysfunction in older women. Several clinical trials
      employing oral estrogen therapy have also observed that some aged women with
      senile dementia have improved cognitive and affective function after estrogen
      therapy. Estrogen loss resulting in cognitive disorders, including menopausal
      cognitive dysfunction and senile dementia in late life, may act via several
      mechanisms. Estrogen may be an important growth factor for estrogen-responsive
      neurons. Estrogen therapy may also have substantial neurochemical effects, direct
      effects on the vasculature, and effects on the generation of free radicals, which
      may be toxic to neurons. At this time, several important clinical questions need
      to be answered regarding the role of ERT in the cognitive and affective
      dysfunctions associated with menopause and senile dementia. Should estrogen be
      used for menopausal women whose sole complaint is cognitive or affective
      dysfunction? Does long-term ERT prevent cognitive decline in late life if
      initiated at the time of menopause? Can ERT improve cognition and affective
      function in postmenopausal women with Alzheimer's disease, and does estrogen
      therapy prevent the progression of Alzheimer's disease in these patients?
      Finally, do the vascular effects of estrogen play a role in the treatment or
      prevention of both Alzheimer's disease and vascular dementia?

PMID- 8530716
TI  - Recognition and judgment of facial stimuli in schizotypal subjects.
AB  - Affect recognition abilities, an important component of successful social
      functioning, were examined in two groups of schizotypal subjects who were
      identified by the Perceptual Aberration/Magical Ideation and Physical Anhedonia
      Scales (PABS, MIS, PAS). Prior research has demonstrated social impairments in
      subjects identified by these scales and in schizophrenics. Although research has
      shown schizophrenic subjects to have facial affect recognition deficits, the
      present results did not support the hypothesis that such impairments would appear
      in subjects exhibiting similar symptoms, but to a less severe degree, when
      compared with controls. The results suggest that deficits in emotional decoding
      may appear at a relatively late stage in the developmental course of mental
      disorder, or may only be associated with more severe levels of schizophrenia
      spectrum symptomatology. The paper discusses theoretical and methodological
      implications for research on the components and development of social deficits in
      the schizophrenia-spectrum disorders.

PMID- 8530717
TI  - Voice onset time production in French-speaking aphasics.
AB  - VOT productions were compared for 5 Broca's aphasics and 5 Wernicke's aphasics to
      those for a group of 5 normal subjects of similar age. Phonetic errors were
      produced by both types of aphasic patients, but not by normal controls. Although
      previous studies have found significantly more phonetic errors in VOT production
      for Broca's aphasics, this study did not. Both Broca aphasics and Wernicke
      aphasics had somewhat less overall average difference in VOT between voiced and
      voiceless consonant pairs than normal speakers. Standard deviations associated
      with the VOT productions were also greater for both aphasic groups than for
      normal subjects. The results of this study are considered in light of the
      previous literature.

PMID- 8530718
TI  - Effect of single and combined altered auditory feedback on stuttering frequency
      at two speech rates.
AB  - The purpose of this study was to determine if combining delayed auditory feedback
      (DAF) and frequency altered feedback (FAF) would enhance fluency more than either
      DAF or FAF alone. Ten stutterers read at normal and fast speech rates under
      nonaltered auditory feedback (NAF), DAF (i.e., a 50 ms delay), FAF (i.e., a one
      half octave downward shift), and a combination of DAF and FAF [(COMBO), i.e., a
      50 ms delay plus a one half octave downward shift]. Results indicated that
      stuttering frequency was significantly reduced under all altered auditory
      conditions at high speech rates relative to the NAF condition. There were,
      however, no significant differences between the altered auditory feedback
      conditions (i.e., DAF, FAF, and COMBO). It is suggested that further studies be
      undertaken to explore the combination of altered auditory feedback conditions, as
      it may be the case that a floor effect was demonstrated with the singular
      presentations of DAF and FAF and further improvements in fluency enhancement
      could not be exhibited in the combined condition. Finally, these findings support
      the notion that a slowed rate of speech is not necessary for fluency enhancement
      under conditions of altered auditory feedback.

PMID- 8530719
TI  - An introduction to logistic regression with an application to the analysis of
      language recovery following a stroke.
AB  - The aim of a statistical model is to present a simplified representation of the
      underlying structure in a data set by separating systematic features from random
      variation. Sometimes the purpose of a statistical model is to provide a simple
      descriptive summary of the data and sometimes it is to use the data for
      comparative or inferential purposes. In practice, the specification of a
      statistical model requires a thorough understanding of the substantive area of
      application, an assessment of the validity of the assumptions of the model, and
      an evaluation of the fit of the model to the data. In this paper, as an
      illustration of these aspects of the statistical modeling of data, we consider
      the specification, application, and interpretation of a logistic regression model
      for the investigation of relationships between binary response data and a
      collection of explanatory variables. We illustrate applications of the
      methodology using data from a prospective study of spontaneous language recovery
      following a stroke (Holland, Greenhouse, Fromm, & Swindell, 1989).

PMID- 8530720
TI  - Inferential abilities of normal and right hemisphere damaged adults.
AB  - There were two aims of this study. The first was to compare indirect inferencing
      abilities by nine right hemisphere brain-damaged (RHD) adults with 18 matched
      normal controls. The second purpose was to determine the best condition in which
      to present information to the RHD individuals for the purpose of forming these
      inferences. Three conditions were evaluated: (1) Auditory-Only, (2) Orthographic
      Only, and (3) Combined Auditory/Orthographic. It was hypothesized that right
      hemisphere damaged persons would perform most successfully when the materials
      (narrative paragraphs) were presented using the combined condition. Both groups
      performed significantly better in the combined Auditory/Orthographic condition.
      There were no significant differences in the performances of the RHD group as
      compared to the normal controls. This suggested that the RHD group did not
      exhibit an inference impairment on this type of linguistic task.

PMID- 8530721
TI  - Disorders of nasality in subjects with upper motor neuron type dysarthria
      following cerebrovascular accident.
AB  - The nasality of 19 subjects with upper motor neuron (UMN) damage following
      cerebrovascular accident (CVA), and 19 control subjects matched for age and sex,
      was investigated using both perceptual judgements of nasality and a modified
      version of the nasal accelerometric procedure described by Horii (1980). Nasality
      indices were calculated for each subject during the production of a series of
      nasal and non-nasal sounds, words, and sentences. Statistical comparison of the
      two groups revealed that the CVA subjects had significantly higher nasality
      indices on the production of nonnasal speech tasks than the controls. No
      significant difference was noted between the two groups on nasal tasks.
      Individual case by case examination of the accelerometer data confirmed the
      presence of hypernasality in 7 of the 19 CVA subjects. In contrast to the
      instrumental findings, the results of the perceptual judgements of nasality
      identified the presence of hypernasality, hyponasality, and normal nasal
      resonance within the CVA group.

PMID- 8530722
TI  - Clinical and semiquantitative marginal analysis of four tooth-coloured inlay
      systems at 3 years.
AB  - OBJECTIVES: The marginal quality of four tooth-coloured inlay systems was
      clinically investigated and subjected to computer-aided semiquantitative marginal
      analysis under scanning electron microscopy (SEM) after 3 years of clinical
      service. METHODS: Three of the restoration types were made using the Cerec CAD
      CAM apparatus: one was milled from preformed glass ceramic blocks, and the two
      other inlay types were milled from preformed porcelain blocks. The fourth system
      was based on an experimental indirect resin composite inlay system. Each inlay
      type was luted with a different luting resin composite. The clinical evaluation
      was performed with a mirror and explorer by two clinicians separately, and the
      marginal analysis was conducted microscopically on replicas (SEM x 200). RESULTS:
      After 3 years in situ, all the restorations were clinically acceptable. No
      recurrent caries was observed. Marginal analysis under SEM detected a high
      percentage of submargination for all four systems, which suggests that their
      respective resin composite luting agents were all subject to wear. The percentage
      of marginal fractures on the enamel side as well as on the inlay side did not
      increase dramatically compared to the 6-month results. CONCLUSION: The first
      recall after 6 months of clinical service indicated how tooth-coloured inlays
      behave at their margins. The 3-year results confirmed the early findings,
      indicating that wear of resin composite lutes is important and present in all
      systems. The two ceramic materials showed a similar behaviour at the margins. The
      resin composite inlay performed better at the inlay site than at the enamel site.

PMID- 8530723
TI  - Seroepidemiology of herpes virus infections among dental personnel.
AB  - OBJECTIVES: To examine the possible occupational hazard of infection with human
      herpes viruses among dental personnel. METHODS: Sera from 81 preclinical dental
      students, 53 clinical dental students and 103 qualified dental surgeons were
      tested for antibodies to herpes simplex virus type 1 (HSV-1), cytomegalovirus
      (CMV), Epstein-Barr virus (EBV) and human herpes virus type 6 (HHV-6). The same
      number of control subjects, matched individually for age (+/- 1 year), sex and
      social class, was also examined. Antibodies were detected by ELISA for HSV-1,
      latex agglutination for CMV, indirect immunofluorescence with P3HR1 cells for EBV
      and indirect immunofluorescence with infected JJhan cells for HHV-6. Each
      participant also completed a questionnaire to permit correlation of demographic
      data and risk factors with serological results. RESULTS: No significant
      difference in seroprevalence was detected between any of the dental groups and
      their respective controls. There was a significantly higher prevalence of
      antibodies to EBV among clinical students (P = 0.02) and qualified dentists (P =
      0.0003) than among preclinical students. These significant increases were not
      mirrored in the three corresponding control groups. CONCLUSION: The results
      suggest a possible occupational risk of infection with EBV in dentists. There was
      no evidence for a significant risk of occupational infection with HSV-1, CMV or
      HHV-6.

PMID- 8530724
TI  - Initial study of periodontal status in non-insulin-dependent diabetics in
      Mauritius.
AB  - OBJECTIVES: Investigation of Mauritian non-insulin diabetic periodontal health.
      METHODS: In Port Louis, the capital of Mauritius, 24 patients with non-insulin
      dependent diabetes mellitus were matched by age with 24 controls. Because
      matching was incomplete for gender and race, the groups were treated as
      independent for data analysis. Operator-blind scores were recorded for the
      presence of plaque, bleeding on probing, probing depth, recession and probing
      attachment level. RESULTS: When variations in plaque and age were taken into
      account, there was a significant difference in probing attachment level between
      the groups (diabetic mean = 4.16 mm, control mean = 3.09 mm), and an effect of
      gender on gingival bleeding which may relate to tobacco smoking. CONCLUSION: In
      an isolated community with a 13% prevalence of NIDDM, this study confirms
      previous periodontal findings regarding the effect of the disease.

PMID- 8530725
TI  - Timing of first restorations in permanent teeth: a new system for oral health
      determination.
AB  - OBJECTIVES: A system of oral health determination in which times between eruption
      of teeth and first restorations because of caries is measured is applied in a
      retrospective analysis of oral health data relating to rural health centres in
      Finland. METHOD: The retrospective analysis was carried out using data relating
      to three health centres in different parts of Finland. The times between eruption
      and the placement of the first restorations in subjects up to 18 years of age
      were investigated. RESULTS: Between 10% and 25% of all permanent molar teeth were
      filled in the year of tooth emergence--the 'immediate posteruptive step'. A
      steadily increasing restoration placement rate--the 'ascending growth phase'--was
      observed after the 'posteruptive step'. The restoration rate was found to plateau
      5-8 years after eruption--the 'retardation phase'. CONCLUSIONS: Restoration
      increment curves with longitudinal measurements are believed to be a sensitive
      indication of oral health at both individual and population levels.

PMID- 8530726
TI  - Radiographic detection of overhangs formed by resin composite luting agents.
AB  - OBJECTIVES: An in vitro model was used to assess the ability of standard
      radiographic techniques to detect marginal overhangs of resin composite luting
      agents beside porcelain and resin composite inlays. METHODS: The radiodensity of
      five commercially available luting resins was determined using ISO 4049
      methodology. For four of the luting agents, artificial overhangs (0.5 x 0.5 x 2
      mm) were created at the cervical margin of standard resin composite and porcelain
      inlays. Radiographs were recorded, using wax as a tissue equivalent, and the
      overhangs reduced incrementally in depth by 0.5 mm with serial images at each
      depth. The images were assessed in random sequence by three observers. RESULTS:
      There were significant differences between the radiopacity of the luting resins.
      These correlated well with the ability of the observers to detect marginal
      overhangs adjacent to resin composite inlays. CONCLUSIONS: Even with the most
      radiopaque luting material, a substantial marginal ledge could not be detected in
      association with a radiopaque resin composite inlay. The threshold for detection
      of the overhang was lower when using a radiolucent porcelain inlay.

PMID- 8530727
TI  - A laboratory evaluation of Ektaspeed Plus dental X-ray film.
AB  - OBJECTIVES: The aim of this study was to make a laboratory evaluation of the
      image quality of a new dental X-ray film, Ektaspeed Plus, compared with Ektaspeed
      and Ultraspeed films. METHODS: Films of each emulsion type underwent a range of
      exposures at both 50 kVp and 70 kVp, and characteristic curves were constructed
      to give a comparison of fog, speed and contrast. Line pair and contrast detail
      test objects were used to assess the resolution of radiographs and the ability of
      the two film types to reproduce minor differences in subject contrast. The
      sensitivity of the emulsions to safelighting for a range of times was also
      tested. RESULTS: Ektaspeed Plus had the same speed, a slightly higher base plus
      fog density but a higher contrast (50 and 70 kVp) than Ektaspeed. The speed of
      Ektaspeed Plus was higher and the contrast similar to that of Ultraspeed film.
      Limiting resolutions of the three films were the same. There was a slightly
      better imaging of one contrast detail phantom with Ektaspeed Plus compared to
      Ektaspeed at 70 kVp only. All three emulsions were insensitive to recommended
      safelighting conditions. CONCLUSION: The improved image contrast of Ektaspeed
      Plus may be more acceptable to dentists than Ektaspeed and lead to a greater
      acceptance of E-speed film, contributing to dose reduction.

PMID- 8530728
TI  - Duration of cleaning and priming of dentine and contraction gap formation.
AB  - OBJECTIVES: The effects of the duration of cleaning and priming on the marginal
      adaptation of a light-activated resin composite in a cylindrical dentine cavity
      were examined by measuring the width of the wall-to-wall polymerization
      contraction gap. METHODS: The dentine cavity was cleaned with ethylene diamine
      tetra-acetic acid (EDTA) and primed 35 vol% hydroxyethyl methacrylate (HEMA) or
      glyceryl methacrylate (GM) solution for up to 60 s. The cavity was filled with a
      light-cured resin composite after the application of a dual-cured dentine bonding
      agent. RESULTS: The formation of a contraction gap by the composite appeared to
      be prevented completely, regardless of the duration of priming with GM solution,
      when the cavity was cleaned with EDTA for 60 s. When cleaning was limited to just
      30 s, GM priming had to be prolonged to 60 s to obtain complete marginal
      integrity. A significantly wide contraction gap was observed without EDTA
      cleaning, even when the cavity wall was primed with GM solution for 60 s.
      CONCLUSION: GM solution was a better dentine primer than HEMA solution, since
      HEMA priming did not prevent gap formation under any of the conditions tested.

PMID- 8530729
TI  - Influence of light irradiation of dentine primers on dentine-resin bond.
AB  - OBJECTIVE: The purpose of this study was to examine the influence of light
      irradiation of dentine primers that contain camphoroquinone (CQ) on the shear
      bond strength to dentine and their contact angle. METHOD: Three dentine bonding
      systems which contain CQ, Imperva Bond, OptiBond and XR-Bond; and Light Bond,
      which does not contain CQ, were employed. Labial surfaces of freshly extracted
      lower bovine incisors were ground with no. 600 grit SiC paper. Dentine primers
      were applied to the dentine surfaces in two groups, irradiated and non
      irradiated. A shear bond strength test was performed and the direct contact angle
      was measured. RESULTS: Statistical analysis (Newman-Keuls multiple comparison P <
      0.05) of the data indicated that light irradiation of the dentine primer for
      systems containing CQ resulted in increased bond strength and decreased contact
      angle. CONCLUSION: This study indicates that for these dentine bonding systems
      containing CQ in their primers, light irradiation of the dentine primer is
      effective in improving wettability and increasing the bond strength to dentine.

PMID- 8530731
TI  - Dental science: the importance of maintaining balanced research programs.

PMID- 8530730
TI  - The effectiveness of an indicator gel in the detection of exposed dentine.
AB  - OBJECTIVES: To investigate the effectiveness of an indicator gel in revealing
      exposed dentine. METHODS: Teeth prepared into dentine and then stained with the
      indicator gel were sectioned for histological examination. RESULTS: The indicator
      gel was found to stain dentine and thin layers of enamel. CONCLUSION: The gel is
      suggested to be an effective indicator as an aid to acid etching and in the
      preparation of teeth for resin-bonded restorations.

PMID- 8530732
TI  - Discovering Canada's oral tradition: dental research in the second half of the
      20th century.

PMID- 8530733
TI  - Statistical issues in periodontal research.
AB  - In the past 10 to 12 years, there have been several statistical issues identified
      in periodontal research which require and have generated non-standard or new
      statistical approaches. The purpose of this paper is to give an overview of these
      issues and approaches. Three general categories of issues are described: (i)
      statistical methods for detecting when disease progression occurs, and biological
      theories and corresponding statistical models which attempt to describe how the
      disease progresses; (ii) design issues in studies of therapeutic efficacy; and
      (iii) analytic issues arising from periodontal data analysis.

PMID- 8530734
TI  - Jaw pain prevalence among French-speaking Canadians in Quebec and related
      symptoms of temporomandibular disorders.
AB  - The purpose of this study was to assess the prevalence and pattern of self
      reported TMD jaw pain in a randomized stratified sample from the general
      population living in the Province of Quebec, Canada. Through a telephone survey,
      standardized questions were asked to 897 French-speaking respondents, aged 18
      years old and over, regarding frequency, severity, daily pattern of jaw pain,
      presence of difficulty in opening, joint clicking, and sleeping problems. All
      prevalence estimates were adjusted to the sociodemographic distribution of the
      non-institutionalized population. The results indicate that TMD jaw pain is self
      reported by 30% of the general population; however, the prevalence of cases
      reporting frequent episodes (quite often or very often) is estimated at 7%, with
      more than two-thirds (69%) of the respondents in this subgroup experiencing
      moderate to severe pain. The prevalence rates of frequent difficulty in opening
      and joint clicking were estimated at 9% and 4%, respectively. Approximately one
      in four subjects with frequent episodes of jaw pain also reported frequent joint
      clicking or difficulty in opening, and a strong association (Gamma coefficient >
      0.6) was found among all three TMD symptoms. Our data suggest that the prevalence
      of clinically significant TMD-related jaw pain (frequent jaw pain of moderate to
      severe intensity) is approximately 5% in the general population of the Province
      of Quebec. In the nine months preceding the survey, about 2% of the total
      population sought treatment for a TMD symptom.

PMID- 8530735
TI  - Tensile strength of thin resin composite layers as a function of layer thickness.
AB  - As a rule, cast restorations do not allow for free curing contraction of the
      resin composite luting cement. In a rigid situation, the resulting contraction
      stress is inversely proportional to the resin layer thickness. Adhesive
      technology has demonstrated, however, that thin joints may be considerably
      stronger than thicker ones. To investigate the effects of layer thickness and
      contraction stress on the tensile strength of resin composite joints, we cured
      cylindrical samples of a chemically initiated resin composite (Clearfil F2) in
      restrained conditions and subsequently loaded them in tension. The samples had a
      diameter of 5.35 mm and thicknesses of 50, 100, 200, 300, 400, 500, 600, and 700
      microns, 1.4 mm, or 2.7 mm. None of the samples fractured due to contraction
      stress prior to tensile loading. Tensile strength decreased gradually from 62 +/-
      2 MPa for the 50-microns layer to 31 +/- 4 MPa for the 2.7-mm layer. The failures
      were exclusively cohesive in resin for layers between 50 and 400 microns thick.
      Between 500 and 700 microns, the failures were cohesive or mixed
      adhesive/cohesive, while the 1.4- and 2.7-mm layers always failed in a mixed
      adhesive/cohesive mode. For the resin composite tested, the contraction stress
      did not endanger the cohesive strength. It was concluded that if adhesion to
      tooth structure were improved, thinner adhesive joints might enhance the clinical
      success of luted restorations.

PMID- 8530736
TI  - The influence of bur blade concentricity on high-speed tooth-cutting
      interactions: a video-rate confocal microscopic study.
AB  - This study aimed to determine the degree of eccentricity between different
      tungsten carbide bur manufacturing techniques and to study the effect of bur
      inaccuracy on dental enamel. Error in bur concentricity may arise from
      malalignment of the steel shaft and carbide head in a two-piece construction bur.
      Cutting blades rotate at multiple radii from the shaft axis, potentially
      producing vibrations and damage to the cut substrate. Techniques now allow for
      the manufacture of one-piece tungsten carbide burs with strength adequate to
      withstand lateral loading. A comparison of tungsten carbide dental cutting tools
      revealed the true extent of concentricity errors. Variation in alignment of the
      cutting head and shaft in the two-part constructions incurred between 20 and 50
      microns of additional axial error. High-speed cutting interactions with dental
      enamel between carbide burs were studied by means of a video-rate confocal
      microscope. A cutting stage fitted to a Tandem Scanning Microscope (TSM) allowed
      for real-time dynamic image acquisition. Images were captured and retrieved by
      means of a low-light-level camera recording directly to S-VHS videotape.
      Videotape showing the interactions of high-speed rotary cutting instruments (at
      120,000 rpm) were taken under simulated normal wet-cutting environments, and the
      consequent damage to the tooth tissue was observed as it occurred. Concentrically
      engineered bur types produced a superior quality cut surface at the entry, exit,
      and advancing front aspects of a cavity, as well as less subsurface cracking.
      Imaging of the coolant water film local to recent cutting operations showed
      regular spherical cutting debris of 6 to 18 microns diameter from the concentric
      tools, whereas the less-well-engineered burs produced ragged, irregular chips,
      with 25-40 microns diameter debris, indicating far more aggressive cutting
      actions. This study has shown that there is reduced substrate damage with high
      concentricity carbide burs.

PMID- 8530737
TI  - High-resolution and analytical electron microscopic studies of new crystals
      induced by a bioactive ceramic (diopside).
AB  - Diopside has been developed for use in dental root implants and for the filling
      of bone defects. In previous studies, diopside developed hydroxyapatite (HA) on
      its surface and achieved a direct bond with bone. The purpose of this study was
      to investigate the mechanism of crystal formation on the diopside surface. We
      ultrastructurally evaluated the interface between new diopside-induced crystals
      and diopside. Specimens were prepared in three experiments: (1) Granular diopside
      was immersed in simulated body fluid (SBF); (2) granular diopside was implanted
      into a cavity in rabbit bone; and (3) a diopside dental root implant was
      implanted into a Japanese monkey. The specimens were examined by contact
      microradiography, high-resolution transmission electron microscopy, and
      analytical electron microscopy. In the experiment with SBF, many platelet-like
      crystals formed in the diopside surface layer. The lattice of diopside and that
      of the new crystals were very close, but no clear continuation of the lattice was
      observed. In the experiments which used a rabbit and a monkey, contact
      microradiography showed close contact between bone and diopside. High-resolution
      transmission electron microscopy revealed crystal growth from the diopside
      surface layer, and continuity between the diopside lattice and that of the new
      crystals. The morphological characteristics of the new crystals and the results
      of these analyses suggest that these new crystals are HA. With regard to the
      mechanism by which crystals are formed on the diopside surface layer, it is
      possible that epitaxial crystal growth could originate as a nucleus on the
      surface. In this case, epitaxial crystal growth of primarily octacalcium
      phosphate (OCP) may have occurred, and this may have changed to HA by a phase
      transition. However, epitaxial growth of OCP on the diopside surface is still
      highly speculative, since there is no direct supporting evidence.

PMID- 8530738
TI  - Reversible structural changes of octacalcium phosphate and labile acid phosphate.
AB  - Acid phosphate is one of the major impurities incorporated into bioapatites, and
      its quantity and environment in forming mineral have been used as diagnostic
      probes to pursue acidic precursor(s). Currently, little is known about the
      structural feature of nonstoichiometric octacalcium phosphate (OCP), which has
      been advocated to be, most plausibly, mineral salt initially formed during
      amelogenesis. In the present report, we attempt to define the state of acid
      phosphate in OCP crystals which were Ca-deficient and contained 40% total
      phosphate as acid phosphate. We assessed fractions of acid phosphate in discrete
      environments by extracting the crystals in either deionized water, 10 mmol/L NaOH
      solution (initial pH 11), or 150 mmol/L Tris buffer at pH 7.4. Solid samples
      before and after the treatments were examined by chemical analyses and x-ray
      diffraction. The results indicated that successive extractions with use of the
      alkaline solution brought about a reversible change (not hydrolysis) in the
      interior structure of OCP, which accompanied a marked decrease in acid phosphate.
      A substantial part of the lost acid phosphate was restored during subsequent
      treatments at neutral pH, and, intriguingly, this restoration accompanied a re
      ordering of OCP structure. The data suggested that the acid phosphate in OCP is
      separated into three pools: (a) a stable pool corresponding to roughly 50 to 60%
      of the total acid phosphate, (b) a reversibly exchangeable pool corresponding to
      25 to 30% of the acid phosphate which may exist either in the water layer or on
      crystal surfaces, and (c) an unstable (or irreversibly lost) pool corresponding
      to 15 to 20% of the acid phosphate, a part of which might be explained by the
      presence of excess hydrogen in OCP. The present work supports the concept that
      protons and, to a lesser magnitude, phosphate species can diffuse into and out of
      the OCP lattice prior to initiation of its hydrolytic transition into apatite.

PMID- 8530739
TI  - Mineral element analysis of carious and sound rat dentin by electron probe
      microanalyzer combined with back-scattered electron image.
AB  - We recently demonstrated the advantages of back-scattered electron images (COMPO)
      in the visualization of dentinal caries, and the relationship of the change in
      the dentin fluorescence pattern in caries lesions. However, the exact nature of
      these changes is not known. In this paper, the nature of the changes in the areas
      with reduced mineral content in COMPO images was investigated. We examined the
      relation of changes in mineral elements and the appearance of soft carious and
      sound dentin in COMPO images using a scanning electron microscope (SEM) equipped
      with an electron probe microanalyzer (EPMA). Rat molars with small dentinal
      caries lesions just under the DEJ were chosen for the study. The Ca, P, Na, Mg,
      Zn, F, and total contents were determined by EPMA from five different dentin
      sites, and the Ca/P and Mg/Ca ratios were calculated. Generally, the lowest
      contents were found in caries lesions and highest in mantle dentin, with the
      exceptions of Mg and Zn. The Ca/P ratio was lowest in mantle dentin and highest
      in carious dentin. The results confirm that the change in fluorescence in the
      dentinal caries lesion is correlated with the very initial changes in mineral
      content, and that EPMA used in combination with COMPO images is a useful tool for
      determining small changes in mineral elements in the carious and adjacent areas
      of dentin.

PMID- 8530740
TI  - The distribution of fluoride in carious human enamel.
AB  - The proton probe has been used to map F concentration changes in the enamel of 15
      teeth showing clinical evidence of caries. Thin sections through the lesions were
      microradiographed and measurements made of the surface zone (radiodense) and body
      (radiolucent) areas. Each section was then scanned with a focused beam of 2.5 MeV
      protons, 2000 spot analyses being performed over areas up to 2 x 3 mm. F was
      determined by detecting gamma rays from a nuclear reaction and the data used to
      construct 3-D surface plots. The maximum F concentration in the lesion surface
      zone was extremely variable, ranging from 1750 to 21,700 ppm, and rarely occurred
      over the deepest part of the lesion. F levels were elevated in the lesion body
      but usually to a small extent only. A large increase in F throughout the lesion
      body was found in 3 lesions only, and was associated with a surface zone that was
      thin or of low x-ray density. Relatively small F increases in the lesion body
      were associated with either a thick, x-ray dense surface layer having a greatly
      increased F level (> 10,000 ppm) or, conversely, with a surface layer having a
      relatively small F increase. Since F uptake can be regarded as a "marker" of past
      remineralization events, this study shows that remineralization can and does
      occur in the body of natural enamel caries lesions, especially when the surface
      layer is thin or lost. Fluoride availability that encourages the formation of an
      extremely dense surface layer may result in under-achievement of this natural
      repair process in the lesion body.

PMID- 8530741
TI  - Collagen biosynthesis in human oral submucous fibrosis fibroblast cultures.
AB  - To investigate the mechanism of collagen accumulation in oral submucous fibrosis
      (OSF) tissues, we examined the biosynthesis of collagen in fibroblast cultures
      established from OSF lesions. Fibroblasts obtained from four of ten OSF specimens
      showed more than a 1.5-fold increase in the production of collagens compared with
      fibroblasts from age-, sex-, and passage-matched normal controls (p < 0.05). When
      the relative amounts of collagen synthesis were estimated by SDS polyacrylamide
      gel electrophoresis, it was found that both OSF and control cells produced about
      85% type I collagen and 15% type III collagen. The ratio of alpha 1(I) to alpha
      2(I) chains was about 3:1 in OSF cells instead of the 2:1 expected for type I
      collagen. The excess alpha 1(I) chains could mean that collagen type I trimer was
      synthesized by the fibroblasts. These findings suggest that collagen
      overproduction and a reduced degradation of the structure-stable collagen type I
      trimer synthesized by OSF fibroblasts might contribute to the accumulation of
      collagen in OSF lesions in vivo. The mechanism(s) of increased procollagen
      production were analyzed by Northern blot, slot blot, and Southern blot. The OSF
      fibroblast strains with elevated collagen production also contained higher-than
      normal levels of procollagen mRNA, and the ratios of alpha 1(I), alpha 2(I), and
      alpha 1(III) procollagen mRNAs were compatible with the results of corresponding
      procollagen alpha chains. The gene copy number of pro alpha 2(I) collagen gene in
      OSF fibroblasts was about 1.05. No gene amplification was found. These results
      indicate that expression of these procollagen genes in cultured fibroblasts is
      regulated at the transcriptional level.

PMID- 8530742
TI  - Salivary levels of suspected periodontal pathogens in relation to periodontal
      status and treatment.
AB  - The primary ecological niche for suspected periodontal pathogens seems to be the
      subgingival area, even though periodontal pathogens are also frequently recovered
      from saliva. The interrelationship of different periodontal conditions and the
      salivary levels of suspected periodontal pathogens is not known. In the present
      study, salivary levels of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis, Prevotella intermedia, Campylobacter rectus, and Peptostreptococcus
      micros were determined by bacterial culture and related to clinical periodontal
      status in 40 subjects with either advanced, moderate, or initial/no
      periodontitis. Culture-positive subjects harbored the 5 bacterial species in mean
      numbers ranging from 2 x 10(5) to 6 x 10(7) colony-forming units (CFU)/mL saliva.
      A. actinomycetemcomitans was found in none and P. gingivalis in one of the
      subjects with initial periodontitis, whereas both species were found in 33% and
      44%, respectively, of the subjects with moderate periodontitis and in 60% and
      40%, respectively, of the subjects with advanced periodontitis. The mean numbers
      of CFU/mL of P. intermedia, C. rectus and P. micros were significantly higher in
      subjects with advanced periodontitis than in subjects with initial/no
      periodontitis. Ten patients with advanced periodontitis were treated mechanically
      and with adjunctive systemic metronidazole, and were re-examined 1 and 6 months
      after treatment. Periodontal treatment eradicated or significantly reduced the
      levels of salivary periodontal pathogens for half a year, whereas in untreated
      subjects, the levels and the detection frequencies generally remained fairly
      stable. In conclusion, the results showed that the salivary levels of periodontal
      pathogens reflect the periodontal status of the patient.

PMID- 8530743
TI  - Simultaneous detection of Actinobacillus actinomycetemcomitans and Porphyromonas
      gingivalis by a rapid PCR method.
AB  - The identification of periodontal pathogens by conventional methods is time
      consuming and difficult. Therefore, a multiplex PCR method for simultaneous
      detection of Actinobacillus actinomycetemcomitans (A.a.) and Porphyromonas
      gingivalis (P.g.) was developed for rapid and easy determination of these risk
      indicator bacteria in human periodontal disease. The PCR primers were designed to
      hybridize to various regions of 16S rRNA genes, and a hot-start technique was
      used to obtain maximum sensitivity and specificity. This method can detect both
      of these bacteria in subgingival plaque samples at concentrations as low as 5 to
      50 cells per sample. The sensitivity, however, was even 10 times better when the
      bacteria were analyzed in a water suspension. Since the only step between sample
      collection and the actual analysis is a brief centrifugation of the patient
      sample, the detection can be readily carried out in four hours. The performance
      of the method was studied with 36 patient samples. The results showed that the
      PCR method detected A.a. (44% vs. 25%, respectively) and P.g. (56% vs. 42%,
      respectively) more often than the conventional culture in plaque samples. Thus,
      our multiplex PCR method is rapid and more effective than conventional protocols
      in detecting these periodontal pathogens.

PMID- 8530744
TI  - LPS responsiveness in periodontal ligament cells is regulated by tumor necrosis
      factor-alpha.
AB  - Gingival fibroblasts function as accessory immune cells and are capable of
      synthesizing cytokines in response to lipopolysaccharides (LPS) from Gram
      negative microbes. Recently, we have isolated, cloned, and characterized two cell
      lines which exhibit characteristics of periodontal ligament (PDL) cells. In this
      report, we demonstrate that PDL cells showing osteoblast-like phenotype are not
      LPS-responsive cells. However, treatment of PDL cells with tumor necrosis factor
      alpha (TNF-alpha) inhibits the expression of their osteoblast-like
      characteristics. As a consequence of this TNF-alpha-induced phenotypic change,
      PDL cells become LPS-responsive, i.e., synthesize several pro-inflammatory
      cytokines in response to LPS. These phenotypic changes occur at concentrations of
      TNF-alpha that are frequently observed in tissue exudates during periodontal
      inflammation, suggesting a physiological significance for these in vitro
      observations. It is of interest that TNF-alpha-induced phenotypic changes in PDL
      cells are transient, since removal of rhTNF-alpha from the supernatants of PDL
      cell cultures results in re-acquisition of the osteoblast-like characteristics
      and lack of LPS responsiveness of PDL cells. These results suggest that TNF
      alpha, by regulating the PDL cell functions, may allow these cells to participate
      in the disease process as accessory immune cells at the expense of their
      structural properties.

PMID- 8530745
TI  - Expression of transglutaminase C during the prenatal development of human
      submandibular glands.
AB  - The involvement of transglutaminase C (TGase C) in morphogenesis and
      cytodifferentiation during glandular tubule formation was addressed by
      immunolocalization of the protein at different stages of prenatal human
      submandibular gland development in 100 fetuses and 20 adult salivary glands.
      Immunocytochemical detection was carried out using a monospecific antibody to
      TGase C. The results showed TGase C reactivity in both acini and ducts early in
      development (from 10 to 14 weeks), followed by a marked increase in ductal
      activity and a decline in acinar activity up to 32 weeks. During the peak of
      reactivity at 25 to 32 weeks, staining was concentrated in the apical ends of the
      columnar cells. In the adult, staining was weakly and diffusely distributed in
      the striated and excretory ducts. Western blot analysis of the cellular extracts
      of pooled samples from various stages of salivary gland development showed a
      single strong band at 76 kDa early in development. This band became weaker after
      32 weeks of prenatal development and in the adult. These findings of transient
      high expression of TGase C, which coincide with the development of tubulo
      alveolar structure, suggest that TGase C may play a role in morphogenesis in
      human salivary gland development.

PMID- 8530746
TI  - A profile of patients in six dental school clinics and implications for the
      future.
AB  - Surveys were conducted of patients receiving care at six dental school clinics in
      the United States during a one-week period in the fall of 1993. Survey data were
      analyzed to determine who was using services provided by these dental schools,
      the types of services being provided, and why people chose to receive their care
      at these dental schools. Eighty-one percent of the patients indicated that low
      cost was an important reason for seeking care at a dental school; the patients
      receiving care at these dental schools tended to be low income. Seventy-six
      percent paid for some or all of their care out of pocket. As dental schools
      reevaluate their mission regarding patient care issues and assess the impact of
      their decisions, information about dental school clinics, particularly who seeks
      care there and why, should be an important consideration.

PMID- 8530747
TI  - Assessment of alcohol and tobacco use in dental schools' health history forms.
AB  - Health history forms are an integral component of students' clinical and didactic
      training in physical assessment and often serve as a model for students to use in
      their future practices. This study examined how alcohol and tobacco use are
      assessed in patient health history forms used in the dental schools of the United
      States and Canada (n = 63). Deans of schools were requested to send a copy of
      their health history and other supplemental forms used for patient care. The
      response rate was 98 percent. Almost 25 percent of the schools' forms did not
      address either alcohol or tobacco use; 37 percent failed to address one or both
      risk behaviors; 25 percent did not request tobacco information; and 36 percent
      did not address alcohol use. Major inconsistencies regarding the inclusion,
      content, and quantity of alcohol and tobacco questions were noted. Consensus
      among dental schools as to which questions to include in their health forms was
      not apparent.

PMID- 8530748
TI  - Contexts for diversity. Papers of the Symposium held at the 72nd Annual Session
      of the American Association of Dental Schools. San Antonio, Texas, March 13,
      1995.

PMID- 8530749
TI  - Effecting change: diversity affects personal and organizational development.

PMID- 8530750
TI  - Clinical contexts for diversity and intercultural competence.

PMID- 8530751
TI  - Creating multicultural dental schools and the responsibility of leadership.

PMID- 8530752
TI  - Policy for diversity: examples from gay men and lesbian inclusion.

PMID- 8530753
TI  - Diversity and multiculturalism: institutional leadership at the University of
      Michigan.

PMID- 8530754
TI  - Contexts for diversity. Reactions.

PMID- 8530755
TI  - Barriers to becoming faculty: word gets out.

PMID- 8530756
TI  - The decline of the golden age: revolutionary change in modern dental education.

PMID- 8530757
TI  - Developmental pathways to schizophrenia: behavioral subtypes.
AB  - This study examined childhood behavior problems in schizophrenic patients and
      their healthy siblings. Childhood Behavior Checklist (T. Achenbach, 1991) ratings
      were obtained from retrospective maternal reports, for 4 age periods: birth to 4
      years, 4 to 8 years, 8 to 12 years, and 12 to 16 years. The results indicated
      that the patients had a variety of childhood behavior problems when compared to
      their siblings and that the various types of problems differed in their
      developmental course. Cluster analysis was conducted on the childhood behavior
      ratings for the schizophrenic patients, and 2 subgroups emerged. Cluster I showed
      more pronounced behavioral problems than Cluster II, and some of these problems
      were apparent in early childhood and increased with age. Cluster I also
      demonstrated greater neuromotor abnormalities in childhood.

PMID- 8530758
TI  - Expectations about arousal and nocturnal panic.
AB  - Expectations about arousal were examined in relation to nocturnal panic (NP).
      Eighteen panic disorder patients suffering from NP attacks and 18 control
      individuals were assigned randomly to conditions in which they were informed that
      audio feedback signals reflected heightened arousal that was either (a) expected
      and harmless or (b) unexpected. Participants relaxed and slept for 45 to 60 min,
      followed by presentation of periodic audio feedback signals. Physiological
      recording was continuous while subjective measures were collected at completion
      of the signals phase. NP patients in the unexpected--no reassurance condition
      were significantly more anxious and symptomatic than their counterparts in the
      expected reassurance condition, whereas control individuals did not differ across
      the 2 conditions. Physiological and behavioral data were less consistent than
      subjective measures. The results are interpreted as supportive of a cognitive
      behavioral model of NP.

PMID- 8530759
TI  - Effects of cognitive load on semantic priming in patients with schizophrenia.
AB  - Schizophrenic and control participants received 2 blocks of trials in each
      experiment. In 1 block they were exposed to regular priming trials (doctor
      nurse), and in another block a nonlexical probe was presented at prime onset for
      40 ms. Regardless of stimulus onset asynchrony (SOA), the schizophrenic patients
      showed hyperpriming when no distrator was present. Paying attention to the
      distracting stimulus reduced priming in the patient group irrespective of SOA.
      Under certain situations, the reduction in priming appeared even when
      participants were asked to ignore the distracting stimulus. Thus, even a
      nonsemantic distractor may be detrimental to schizophrenic patients' language
      processing. That SOA did not modulate the reduction in priming effect is
      consistent with the suggestion that attentional resources are required even with
      short prime-target intervals.

PMID- 8530760
TI  - Autobiographical memory functioning in depression and reports of early abuse.
AB  - The authors investigated the memory functioning of depressed women patients with
      and without a reported history of child physical or sexual abuse using J. M. G.
      Williams and K. Broadbent's (1986) Autobiographical Memory Test. Whereas latency
      to recall autobiographical memories was not related to reports of abuse, patients
      who reported childhood sexual abuse produced more overgeneral memories to
      positive and negative cues. In addition, patients reporting high levels of
      avoidance of spontaneous memories of childhood physical or sexual abuse in the
      past week retrieved more overgeneral memories to positive and negative cues.

PMID- 8530761
TI  - Poor interpersonal problem solving as a mechanism of stress generation in
      depression among adolescent women.
AB  - The authors examined C. Hammen's (1991) model of stress generation in depression
      and the role of interpersonal problem-solving strategies (IPS) in the stress
      generation process in a longitudinal sample of 140 young women who entered the
      study at ages 17-18. Structural equation modeling was used to test a model in
      which IPS and subsequent interpersonal stress mediated the relationship between
      initial and later depressive symptoms. Results supported the main prediction of
      the stress generation model: Interpersonal stress mediated the relationship
      between initial and later depressive symptoms. In addition, IPS predicted
      interpersonal stress. However, no association was found between depressive
      symptoms and IPS. An alternative model in which IPS moderated the relationship
      between stress and depressive symptoms was tested; it was not supported.

PMID- 8530762
TI  - From categorization to classification: a comparison among individuals with
      autism, mental retardation, and normal development.
AB  - Free-sorting, matrix, and class-inclusion tasks were administered to 16
      participants with autism, 16 participants with mental retardation (MR), and 16
      normal children, matched for mental age. On perceptual matrices, participants
      with MR performed less well than those with autism, who performed less well than
      normal children. On functional matrices, participants with autism and those with
      MR performed less well than normal children. Participants with autism performed
      less well than participants with MR and normal children in free-sorting
      representational objects and in the class-inclusion tasks, which require higher
      operational thought. These results suggest that individuals with autism have
      difficulties with tasks that necessitate internal manipulation of information.
      This impairment is discussed in relation to the cognitive deficit characterizing
      autism.

PMID- 8530763
TI  - Sexual abuse histories of adolescent male sex offenders: differences on the basis
      of the age and gender of their victims.
AB  - Childhood sexual abuse has often been implicated in the etiology of adolescent
      sex offending behavior. Victimization rates in the literature vary according to
      whether data are collected prior (22%) or subsequent (52%) to treatment. Previous
      research suggests that the incidence of sexual abuse varies as a function of
      victim age and gender. Sexual abuse histories were collected from 87 adolescent
      male sex offenders following an average of 13 months of clinical interactions.
      Offenders were categorized according to the age and gender of their victims;
      groups were comparable in age and socioeconomic status. It was found that 75% of
      adolescent offenders who ever assaulted 1 male child reported sexual abuse in
      comparison to only 25% of those who assaulted female children, peers, or adults.
      Results suggest that sexual victimization may be an important explanatory
      variable for adolescent sexual assaults against male children.

PMID- 8530764
TI  - Cognitive and neuropsychological characteristics of physically aggressive boys.
AB  - Cognitive-neuropsychological tests were given to adolescent boys (N = 177) to
      investigate processes associated with physical aggression. Factor analysis
      yielded 4 factors representing verbal learning, incidental spatial learning,
      tactile-lateral ability, and executive functions. Physical aggression was
      assessed at ages 6, 10, 11, and 12, and 3 groups were created: stable aggressive,
      unstable aggressive, and nonaggressive. The authors found main effects for only
      the executive functions factor even when other factors were used as additional
      covariates in a step-down analysis; nonaggressive boys performed better than
      stable and unstable aggressive boys. The covariates family adversity and anxiety
      were both related only to the verbal learning factor. This study highlights the
      importance of deficits in executive function in the expression of physical
      aggression relative to other cognitive-neuropsychological functions.

PMID- 8530765
TI  - Autobiographical memory across personalities in dissociative identity disorder: a
      case report.
AB  - A core feature of dissociative identity disorder (DID) is the amnesia that exists
      between personalities. This study investigated autobiographical memory in a
      patient, HS, prior to and after her diagnosis with DID. This diagnosis was
      associated with increased recall of traumatic memories that were reported by a
      child personality. The child personality was able to recognize only half of the
      memories reported by the host personality. HS's responses were dissimilar to
      responses of control and nonexperiment participants. These findings suggest that
      DID is associated with alterations in autobiographical memory and that memories
      differ across personalities. Results are discussed in terms of memory and
      pseudomemory development in DID.

PMID- 8530766
TI  - Social information-processing patterns partially mediate the effect of early
      physical abuse on later conduct problems.
AB  - The authors tested the hypothesis that early physical abuse is associated with
      later externalizing behavior outcomes and that this relation is mediated by the
      intervening development of biased social information-processing patterns. They
      assessed 584 randomly selected boys and girls from European American and African
      American backgrounds for the lifetime experience of physical abuse through
      clinical interviews with mothers prior to the child's matriculation in
      kindergarten. Early abuse increased the risk of teacher-rated externalizing
      outcomes in Grades 3 and 4 by fourfold, and this effect could not be accounted
      for by confounded ecological or child factors. Abuse was associated with later
      processing patterns (encoding errors, hostile attributional biases, accessing of
      aggressive responses, and positive evaluations of aggression), which, in turn,
      predicted later externalizing outcomes.

PMID- 8530767
TI  - Facial expressions of emotion and psychopathology in adolescent boys.
AB  - On the basis of the widespread belief that emotions underpin psychological
      adjustment, the authors tested 3 predicted relations between externalizing
      problems and anger, internalizing problems and fear and sadness, and the absence
      of externalizing problems and social-moral emotion (embarrassment). Seventy
      adolescent boys were classified into 1 of 4 comparison groups on the basis of
      teacher reports using a behavior problem checklist: internalizers, externalizers,
      mixed (both internalizers and externalizers), and nondisordered boys. The authors
      coded the facial expressions of emotion shown by the boys during a structured
      social interaction. Results supported the 3 hypotheses: (a) Externalizing
      adolescents showed increased facial expressions of anger, (b) on 1 measure
      internalizing adolescents showed increased facial expressions of fear, and (c)
      the absence of externalizing problems (or nondisordered classification) was
      related to increased displays of embarrassment. Discussion focused on the
      relations of these findings to hypotheses concerning the role of impulse control
      in antisocial behavior.

PMID- 8530768
TI  - Health policies in Europe: welfare states in a market era.

PMID- 8530769
TI  - States facing interests: struggles over health care policy in advanced,
      industrial democracies.
AB  - Given alarming fiscal imperatives, states and interests in all advanced
      industrial democracies have struggled over health care policy. I explore the
      interface between state autonomy in health care policy and the political
      mobilization of provider interests, especially physicians. Evidence from Germany,
      Japan, Canada, and Great Britain suggests that, longitudinally, policy makers
      everywhere have tried to increase state autonomy in health care, and this has
      generally triumphed over even effectively mobilized providers. The countries that
      have most successfully restrained the growth of health care expenditures--while
      still providing ready access to relatively high-quality care--are those where
      states have most actively restrained both demand- and supply-side system
      interests in policy making. In each country, states have increasingly articulated
      their own greater capacities in health care policy, pushed to do so by the
      imperatives, especially fiscal, embedded in the policy domain.

PMID- 8530770
TI  - Health care reform in The Netherlands: balancing corporatism, etatism, and market
      mechanisms.
AB  - The transformation of the Dutch health care system and the impetus behind the
      market-oriented health care reforms implemented since 1989 are examined. During
      the postwar period, the gradual transformation of the Dutch health care system
      was interrupted twice by attempts to introduce radical reforms: the 1974
      comprehensive health plan and the 1987 pro-competitive national health insurance
      program. The market-oriented reform involves a fundamental change of the
      incentive structure for insurers and providers. The objective is to interest both
      parties in containing costs and improving efficiency while preserving universal
      access through central redistributive financing. In the Dutch political context,
      radical reform proposals can be introduced only by a prolonged series of
      incremental changes, which offer the corporatist organizations of providers and
      insurers ample opportunity to dismantle the original reform design. The 1974
      comprehensive health plan failed largely because of this corporatist trap. The
      1987 market-oriented reform program faced the same risks, although it appeared to
      offer an ingenious political compromise. Private health insurers were
      particularly successful in slowing the reform by frustrating the development of a
      prospective, risk-adjusted payment mechanism. The resistance of corporatist
      organizations to the 1974 and 1987 reforms provoked a largely unplanned process
      of creeping etatization. Paradoxically, the present market-oriented reforms
      coincide with far-reaching state interventions in determining provider fees. A
      new, more satisfactory balance between corporatism, etatism, and market
      mechanisms must still be found.

PMID- 8530771
TI  - The impact of German health insurance reforms on redistribution and the culture
      of solidarity.
AB  - The statutory health care scheme represents the most ambitious branch of the
      German social insurance system because it entails interpersonal redistribution on
      a large scale. The stability of this centerpiece of the German welfare state thus
      depends on a "culture of solidarity" to maintain the legitimacy of these
      redistributions. In this article, the present debate on restructuring the welfare
      state in general is analyzed. However, the focus is on the ongoing struggle to
      further reform the health care system. Influential political actors proposals to
      depart from universal access to a comprehensive range of health care benefits
      based solely on medical need and from the earnings-related mode of financing
      stand in stark contrast to empirical results on insured persons' willingness to
      support the existing system. Findings from qualitative interviews show that a
      culture of solidarity still prevails among insured persons. It is argued that
      lasting political attempts to shift the balance between solidarity and self
      reliance in favor of the latter could weaken this moral infrastructure of the
      welfare state and, as a consequence, the statutory health insurance system could
      lose its plausibility and attraction. Such a development would ease the
      reconstruction of the social security system by privatizing parts of currently
      public expenditures and reducing the scope of interpersonal redistribution.

PMID- 8530772
TI  - Health care reform in Sweden in the 1990s: local pluralism versus national
      coordination.
AB  - Because of the poor state of the Swedish economy, publicly provided health care
      services, like other welfare services, are increasingly vulnerable to possible
      cutbacks. A growing discontent among the public in the late 1980s paved the way
      for experiments with new economic incentives among health care providers.
      Although many parts of the welfare state are being questioned today, the
      principle of universalism in health care has not been seriously challenged, but
      support for the present health care system among Swedes depends on how well the
      system functions. The prospects for implementing major organizational changes in
      health care through a top-down procedure, however, are limited. The appointment
      of the Committee on Funding and Organization of Health Care in 1992 by the
      previous government can be regarded as merely a way to show activity rather than
      as an instrument to achieve meaningful change.

PMID- 8530773
TI  - Health care reform in Norway: the end of the "profession state"?
AB  - From the early nineteenth century until about 1980, a close relationship
      developed in Norway between the state and the medical profession. Medicine became
      integrated into the state at all levels of government, and the profession assumed
      important roles in initiating and formulating health policy. Another, and perhaps
      also causally related, development has been that health policy--and most
      strikingly during postwar expansion--tended to be formulated and implemented in
      its own policy sector, with few links to other parts of the welfare state.
      Important elements of the "profession state" in Norway have thus been
      professional integration with the state and institutional isolation from other
      policy sectors. Health reforms of the 1980s and 1990s brought changes in
      institutional relations: Other professions have replaced physicians as experts at
      central and local levels, and health policy making has become more politicized
      and integrated into welfare state policies. Thus there are clear indications that
      the profession state is waning.

PMID- 8530774
TI  - Prevention and government: health policy making in the United Kingdom and
      Germany.
AB  - The gap between rhetoric and reality in health policy making for disease
      prevention services is well recognized. I do not try once more to close the gap,
      but rather argue that the rhetoric of prevention is politically significant.
      Beginning with an account of prevailing explanations of prevention in policy
      making, I explore the idea that prevention has a pervasive legitimacy in health
      politics. This affords opportunities for instrumental policy making by
      government. To this end, I concentrate on the relationship between disease
      prevention and health care delivery, discussing in detail the association between
      prevention and health care reform. My arguments are based on case studies of
      policy making in Germany and the United Kingdom. I discuss implications for
      understanding the core interests of government, physicians, and users with
      respect to prevention in health policy making. The concluding section offers
      comparative commentary on the role of disease prevention in health sector
      restructuring.

PMID- 8530775
TI  - Three faces of the health care state.
AB  - That health care is a subsystem of the welfare state has dominated the study of
      states and health care policy. But this conception omits two other faces of the
      state--as a putatively democratic organization and as the manager of industrial
      economies in a capitalist world. Policy can be analyzed fruitfully in terms of
      the tensions between these three faces of the health care state.

PMID- 8530776
TI  - Health care reform: where do we go from here?

PMID- 8530777
TI  - A clinical decision rule in the evaluation of acute knee injuries.
AB  - We constructed a clinical decision rule to optimize the use of radiography in
      patients with acute knee injuries. A prospective observational study at a
      university hospital ED was conducted over 10 months. Patients 15 years of age and
      older with acute knee injuries who underwent radiography were included. Patients
      were excluded if they were intoxicated, had distracting injuries, previous knee
      surgery, or open wounds. A standardized closed question data collection
      instrument that recorded 12 historical and 26 physical examination criteria was
      used. Radiographs were interpreted by two radiologists blinded to each other's
      diagnosis. The main outcome parameter was the presence or absence of a fracture.
      We identified 18 fractures in 213 patients (8%). Patients with fractures were
      more likely to have severe joint line tenderness, severe localized swelling, an
      effusion, ecchymosis, flexion < 90 degrees, and an inability to bear weight. A
      clinical algorithm for the use of radiography that requires the presence of
      either an inability to bear weight, an effusion, or an ecchymosis was 100%
      sensitive for the detection of a fracture. All 76 patients without any of these
      criteria did not have a fracture. Limiting knee radiography to patients with
      these criteria would have reduced radiography by 39% without missing a fracture.
      In conclusion, a clinical decision rule for knee radiography that requires the
      presence of either an inability to bear weight, an effusion, or an ecchymosis was
      shown to reduce the need for radiography by 39% while still identifying all
      fractures. Prospective validation of this model is required.

PMID- 8530778
TI  - Measuring the accuracy of the infrared tympanic thermometer: correlation does not
      signify agreement.
AB  - This prospective study assessed the accuracy of the infrared tympanic thermometer
      (ITT) compared to the rectal thermometer (RT) using statistical measures of
      agreement. In a convenience sample of 100 adult emergency department patients,
      ear examinations to assess for cerumen or otitis were followed by temperature
      measurements using the First Temp 2000A thermometer in both ears and the IVAC
      2000 rectally. Left and right ITT temperatures showed high correlation and
      agreement; therefore, only right ITT results are reported. Both the ITT and RT
      recorded similar mean temperatures, standard deviations, and ranges. The
      correlation of the ITT and RT and agreement were below the 0.8 level, indicating
      excellent agreement. The mean temperature difference (RT-ITT) between the two
      devices was 0.1 +/- 0.7 degrees C; in 10% of patients, the temperature difference
      was > or = 1 degree C. Among 10 patients identified as febrile by RT (RT > or =
      38.5 degrees C), 6 were febrile by ITT. Significant differences occurred between
      the temperature measurements using the ITT and RT; these devices do not
      demonstrate excellent agreement.

PMID- 8530779
TI  - Actinobacillus ureae meningitis: case report and review of the literature.
AB  - Actinobacillus urea, formerly known as Pasteurella ureae, is an uncommon
      commensal of the upper respiratory tract in humans. It has been identified as the
      primary pathogen in 10 cases of meningitis and several cases of pneumonia,
      sepsis, and peritonitis. A case is presented that represents another documented
      case of meningitis due to this rare organism. Risk factors associated with
      serious infection due to Actinobacillus ureae and basic management approaches to
      posttraumatic meningitis in general are discussed.

PMID- 8530780
TI  - The perils of bungee jumping.
AB  - Bungee jumping is a relatively new recreational sport. Most emergency physicians
      and trauma surgeons have limited experience with its associated injuries. We
      report the case of a bungee cord attachment apparatus malfunctioning, resulting
      in a free fall of the jumper of approximately 240 feet. The presence of an air
      cushion on the ground prevented significant injury. Knowledge of the potential
      injuries of this new sport is crucial for effective management.

PMID- 8530781
TI  - Fatal pancreatitis as a complication of therapy for HIV infection.
AB  - Acute pancreatitis in HIV-infected patients with or without AIDS has been
      reported with increasing frequency over the past several years. Drugs used to
      treat HIV-infected patients are often the cause. We report a case of a 46-year
      old HIV-infected man who presented to the emergency department with abdominal
      pain and was diagnosed with acute pancreatitis. The patient had recently begun
      taking 2',3'-dideoxyinosine (ddI). He died shortly after admission to the
      hospital; CT scan and autopsy confirmed the cause of death as hemorrhagic
      pancreatitis. We briefly review the literature on the incidence and severity of
      pancreatitis in association with ddI and pentamidine therapy.

PMID- 8530782
TI  - Atheromatous embolism: an unusual case of acute lower extremity ischemia.
AB  - A case is presented of lower extremity ischemia related to atheromatous
      embolization that presumably occurred as a result of passage of an angiographic
      catheter through the aorta. The patient presented with signs and symptoms
      pathognomonic for this entity. Emergency physicians need to be aware of this
      unusual etiology for an ischemic lower extremity.

PMID- 8530783
TI  - Postpartum toxemia: hypertension, edema, proteinuria and unresponsiveness in an
      unknown female.
AB  - Eclampsia, or toxemia of pregnancy, is a disorder of pregnancy characterized by
      seizures associated with hypertension, edema, and proteinuria. Toxemia of
      pregnancy carries significant maternal and fetal morbidity and mortality.
      Eclampsia most commonly occurs in the antepartum period. A minority of cases,
      however, may initially manifest in the postpartum period. We present the case of
      a 28-year-old female with postpartum eclampsia presenting to the Emergency
      Department with altered mental status. A review of the literature concerning
      postpartum toxemia and a discussion of appropriate management strategies follows.

PMID- 8530784
TI  - Visine overdose: case report of an adult with hemodynamic compromise.
AB  - Imidazole decongestants are present in a variety of over-the-counter medications,
      including eye drops and nasal sprays. Their primary mechanism of action is
      vasoconstriction, accomplished by direct stimulation of alpha receptors on blood
      vessels. Accidental and intentional poisonings involving these substances are
      increasing, and can cause mental status and respiratory depression, as well as
      other effects related to alpha receptor stimulation. We present a case of
      tetrahydrozoline ingestion in an adult who presented with chest pain,
      bradycardia, mental status depression, miosis, and other signs and symptoms of
      imidazole compound poisoning. It is important for physicians to be familiar with
      the adverse effects of these ingestions and to be aware of the potential
      therapies for management.

PMID- 8530785
TI  - "Ping-pong" gaze in severe monoamine oxidase inhibitor toxicity.
AB  - Clinical features of monoamine oxidase inhibitor (MAOI) toxicity include
      hypertension, hyperthermia, tachycardia, and muscular agitation. We report two
      cases in which some of these signs of severe toxicity were seen in association
      with a unique periodic alternating gaze disturbance known as "ping-pong" gaze.

PMID- 8530786
TI  - Transient myocardial dysfunction in a child with salicylate toxicity.
AB  - Aspirin overdose may result in acid-base disturbances, electrolyte abnormalities,
      pulmonary edema, chemical hepatitis, seizures, and mental status alteration, but
      myocardial depression has not been reported following aspirin overdose in
      children. In addition to these more typical features, the 13-month-old boy
      reported here developed clinical, radiographic, and echocardiographic evidence of
      myocardial impairment with pulmonary edema and moderately severe global left
      ventricular dysfunction (estimated shortening fraction of 23%). Complete
      resolution of the myocardial dysfunction was demonstrated on follow-up
      echocardiography as the child recovered from the aspirin intoxication. This case
      suggests that myocardial dysfunction can occur as a result of toxic aspirin
      ingestion, and that it may contribute to salicylate-induced pulmonary edema.

PMID- 8530787
TI  - Public relations in disaster management and planning for emergency physicians.
AB  - The goal of this article is to serve as a primer of disaster public relations. It
      will explain the requirements of the media and how best to incorporate their
      ubiquitous presence to the advantage of the disaster team, including how to give
      an effective interview, how and where to establish a media center, and the
      importance of sensing what will make the strongest visual or textual impact. In
      any disaster response, the media will play a large role. Their presence is
      condoned by the law and expected by the public. In reality, a reporter will
      probably arrive at the scene of a disaster before the first health care
      professional. It is only through the knowledge of the media's needs, and an
      appreciation of the ways in which it can assist the disaster team, that planners
      can best forge a relationship with the media that will confer the greatest mutual
      benefit.

PMID- 8530788
TI  - Development of biventricular tachycardia in patient being medically treated for
      stable ventricular tachycardia.

PMID- 8530789
TI  - Moritz Kaposi: idiopathic pigmented sarcoma of the skin.
AB  - Moritz Kaposi first published a description of the entity that bears his name in
      1872, calling it "idiopathic multiple pigmented sarcoma of the skin." For many
      years thereafter, Kaposi's sarcoma was considered to be a relatively rare, slow
      growing malignancy, most commonly seen in middle-aged and elderly men. This
      changed in 1981, with Alvin Friedman-Kein's report of what eventually proved to
      be HIV-associated (epidemic) Kaposi's sarcoma. Kaposi's sarcoma is now one of the
      diagnostic markers of the acquired immunodeficiency syndrome, as well as the most
      common neoplastic complication of that disease. HIV-associated Kaposi's sarcoma
      tends to disseminate widely to mucous membranes and the viscera. Almost all of
      the cases reported in the United States have occurred in homosexual and bisexual
      men, and a number of hypotheses have been suggested to explain this association.
      Over the past several years, however, the incidence of HIV-associated Kaposi's
      sarcoma has declined, and the reasons for this are also uncertain.

PMID- 8530790
TI  - The potential impact of health care reform on emergency department utilization.
AB  - How will emergency department utilization and costs be affected by universal
      coverage provisions? Proponents of health care reform predict that the number of
      ED visits will decline when currently uninsured Americans become eligible for
      primary physicians' care. However, economic concepts indicate the contrary: that
      ED volume and costs will actually escalate upon implementation of health care
      reform initiatives. These basic concepts include: 1) the insulation of most
      consumers from the true cost of health care, fostering higher demands for that
      care; 2) the financial benefits afforded physicians and health maintenance
      organizations by ED's ability, and legal responsibility, to assess and treat any
      patient at any time; and 3) access to ED personnel and material by individuals
      with urgent and nonurgent conditions, which generates fixed costs, regardless of
      patient volume. These effects of health care reform on EDs must be anticipated by
      hospital administrators to avoid compromise of patient care quality and consumer
      satisfaction.

PMID- 8530791
TI  - Examine the head in patients with headaches.

PMID- 8530792
TI  - Air bag "tattoo," a lasting impression.

PMID- 8530793
TI  - The value of self-estimated scholastic standing in residency selection.
AB  - The objective of this study was to determine the degree of association of self
      estimated scholastic standing (self-rank) with an independent evaluation of the
      dean's letter (dean's letter score). Applicants to our emergency medicine
      residency program were asked to estimate their scholastic standing on the
      application form. A blinded independent review of the dean's letter for each
      applicant was performed, and the letter was scored. The final ranking of the
      applicant submitted to the National Resident Matching Program was also obtained.
      Analysis was carried out using the Spearman rank correlation procedure. One
      hundred forty-three medical students with self-rank, dean's letter, and final
      ranking from applications between 1991-1993 were analyzed. The association of
      self-rank with dean's letter score was highly significant. There was also an
      appreciable relationship between self-rank and final rank in the NRMP Match. Self
      rank of scholastic standing by applicants to an emergency medicine residency is
      strongly associated with dean's letter information. Self-rank may be useful
      during early screening of applications before dean's letters are available.

PMID- 8530794
TI  - Objectives to direct the training of emergency medicine residents on off-service
      rotations: surgery, Part 1.
AB  - This is the 34th article in a continuing series of objectives to direct emergency
      medicine resident experiences on off-service rotations. Abdominal and
      gastrointestinal complaints are common problems in the emergency department and
      often lead to consultation with a surgeon. Because an understanding of the
      principles of surgical diagnosis and treatment is an essential component of the
      practice of emergency medicine, residents rotating on surgical services require
      specific goals and objectives to emphasize early patient assessment,
      identification of the possible need for surgery, and a basic understanding of
      definitive management.

PMID- 8530795
TI  - Centralized off-premise transcription service: a model.
AB  - The use of typewritten records in emergency departments can provide better
      documentation and can impact reimbursement, continuous quality improvement, and
      medicolegal aspects of emergency care. An easily accessible system, which
      provides for a uniform, typewritten record within a short turnaround time, has
      been implemented by a private emergency medicine group. The system has had a
      positive impact on reimbursement and efficient patient care. It may also be used
      for teaching and research as well as personal business. A centralized off-premise
      transcription service allows for 24-h dictation for multiple hospitals in a cost
      efficient manner. System drawbacks are minor and start-up problems easily
      overcome.

PMID- 8530796
TI  - Rapid sequence intubation in the emergency department.
AB  - Rapid sequence intubation (RSI) has recently gained wide acceptance among
      emergency physicians (EP). The debate regarding the safety of neuromuscular
      blocking (NMB) agents in the hands of EPs nonetheless remains open, as objective
      studies are few, and all data available so far come from tertiary care centers.
      This retrospective study was done to review our experience with RSI and assess
      the related morbidity and mortality. Two hundred and nineteen intubations were
      done using an RSI protocol during the study period. Hypotension occurred in 24
      patients. Two patients had a short run of bigeminy and 3 had bradycardia. One
      patient went into cardiac arrest unrelated to the use of a NMB agent. Aspiration
      was documented in 3 patients. All patients were successfully intubated. No
      mortality was attributed to the use of muscle relaxants. Our results support the
      safety and effectiveness of RSI in the hands of emergency physicians.

PMID- 8530797
TI  - Use of the laryngeal mask prior to definitive intubation in a difficult airway: a
      case report.
AB  - The laryngeal mask, a relatively new airway adjunct, consists of a large tube
      with an inflatable shallow mask at its distal end which forms a seal around the
      glottic opening. We describe a case of a difficult intubation in the emergency
      department of an obese patient with microagnathia, a short bull neck, and a
      nasopharyngeal hemorrhage in which a laryngeal mask was used to temporarily
      manage the airway prior to definitive intubation. In difficult airway cases where
      it is impossible to ventilate the patient by face mask or intubate the trachea,
      ventilation with the laryngeal mask may be an alternative to transtracheal jet
      ventilation or cricothyrotomy. The laryngeal mask may be useful in managing the
      difficult airway provided that the risks of an inadequate seal, obstruction,
      coughing and laryngospasm, and lack of protection from aspiration are recognized.

PMID- 8530798
TI  - Nontapering versus tapering prednisone in acute exacerbations of asthma: a pilot
      trial.
AB  - Controversy exists as to whether or not the dose of prednisone should be tapered
      in patients discharged from the emergency department after initial treatment for
      an acute exacerbation of asthma. We assessed the rates of relapse and rebound in
      a group of 28 patients treated with a nontapering course of prednisone and
      compared their outcomes to an historical control group of 48 patients treated
      with a typical tapering course of prednisone. We found no significant difference
      in the rates of relapse or rebound between the nontapering dose patients and the
      tapering dose patients within either 21 days of discharge or within 10 days after
      stopping prednisone. Fifty-four percent of study patients reported adverse
      effects that could be attributed to prednisone. Our preliminary findings suggest
      that tapering of prednisone may not be needed in these patients.

PMID- 8530799
TI  - Quality assurance in Canadian emergency departments: a national survey.
AB  - This survey provides a description of quality assurance (QA) in emergency
      departments of Canadian hospitals, looking at QA structure, processes, outcome
      measurements, and applications. With survey questions addressing the existence of
      a written QA plan, chart audits, mortality review, data collection and reporting,
      the frequency of comprehensive QA programs was measured. All Canadian hospitals
      with 200 or more beds were surveyed by mail; 66% responded (134 of 204). Teaching
      and larger hospitals were more likely to respond. QA structure was reported by
      81% of respondents, with 59% of these having a written plan. The majority
      collected data (74%), issued reports (75%), and had QA committees (50%), but only
      34% were computerized. QA processes included chart audits (78%), review of
      laboratory, radiology, or ECG reports (73%, 46%, 54%, respectively), and
      mortality review (91%). Comprehensive QA existed in only 12% of responding
      hospitals.

PMID- 8530800
TI  - The effect of misoprostol on indomethacin-induced renal dysfunction in well
      compensated cirrhosis.
AB  - BACKGROUND/AIMS: Indomethacin has been shown to have adverse effects on renal
      function in patients with well-compensated alcoholic cirrhosis. The aim of this
      study was to determine whether an oral prostaglandin E1 analogue, misoprostol,
      could prevent this indomethacin-induced renal dysfunction. METHODS: Six patients
      with well-compensated alcoholic cirrhosis were studied. Renal hemodynamics and
      tubular function were assessed by clearance techniques before and after an oral
      dose of (i) 50 mg of indomethacin alone (I50), and (ii) a combination of I50 and
      200 micrograms of misoprostol. RESULTS: I50 produced a significant reduction in
      glomerular filtration rate, a fall in effective renal plasma flow and an increase
      in renal vascular resistance. Two hundred micrograms of misoprostol was able to
      abolish the deleterious renal effects of indomethacin totally, yielding an
      increase in glomerular filtration rate and effective renal plasma flow and a
      decrease in renal vascular resistance as well as an increase in urinary volume
      and urinary sodium excretion. These beneficial effects were maximal in the hour
      immediately following medication, but were only transient, and this may be a
      limiting factor in its clinical use. CONCLUSIONS: If the beneficial renal effects
      of misoprostol could be confirmed after chronic administration, then the
      vasodilatory, natriuretic and diuretic potential of 200 micrograms of misoprostol
      could be of potential therapeutic value in patients with well-compensated
      alcoholic cirrhosis who require non-steroidal anti-inflammatory drug therapy.

PMID- 8530801
TI  - Hepato-pulmonary syndrome: successful treatment by transjugular intrahepatic
      portosystemic stent-shunt (TIPS)

PMID- 8530802
TI  - Mycobacteria--related to the aetiopathogenesis of primary biliary cirrhosis?

PMID- 8530803
TI  - Are blotting tests (Riba, western-blot ...) still useful as markers of hepatitis
      C virus infection?

PMID- 8530804
TI  - Individuals with antibodies against hepatitis B core antigen as the only
      serological marker for hepatitis B infection: high percentage of carriers of
      hepatitis B and C virus.
AB  - BACKGROUND/AIMS: Several reports have unequivocally demonstrated that some
      individuals with antibodies against hepatitis B core antigen as the only
      serological marker for hepatitis B infection are chronic carriers of the
      hepatitis B virus. Nevertheless, conflicting data exist about the frequency of
      this phenomenon; its cause is unknown. METHODS: In a prospective study we tested
      individuals who were positive for anti-HBc alone for HBV-DNA as well as for
      coexisting infections with human immunodeficiency virus and hepatitis C virus.
      RESULTS: Using polymerase chain reaction with primer pairs from three different
      regions of the hepatitis B virus genome, we found 54 of 164 individuals (32.9%)
      with anti-HBc alone to be positive for hepatitis B virus, the majority of them
      showing very low hepatitis B virus concentrations. 14.3% were human
      immunodeficiency virus positive; half of them were also hepatitis B virus
      carriers. Surprisingly, 62 of 153 participants (40.5%) in this study showed
      antibodies against hepatitis C virus, and about two thirds of the latter were
      also positive for HCV-RNA. This finding could be confirmed by a retrospective
      analysis of all people tested for hepatitis B virus markers and anti-HCV in our
      institution during the 2 years before the prospective study was begun. Again, a
      high correlation was found between the presence of anti-HCV and anti-HBc alone:
      49.2% of individuals with anti-HBc only were anti-HCV positive also, compared to
      26.8% of HBsAg carriers and only 10% of individuals showing the serological
      pattern of past hepatitis B. CONCLUSIONS: Thus our study of individuals positive
      for anti-HBc alone revealed a high number of carriers of hepatitis B virus and
      hepatitis C virus among them; furthermore, we found some evidence that hepatitis
      C virus infection may favour this unusual hepatitis B virus marker pattern.

PMID- 8530805
TI  - Evaluation of efficacy and safety of thymus humoral factor-gamma 2 in the
      management of chronic hepatitis B.
AB  - BACKGROUND/AIMS: We investigated the antiviral and immunomodulatory effects of a
      combination treatment using thymus humoral factor-gamma 2 and alpha-interferon in
      patients with chronic hepatitis B in whom previous monotherapy with interferon
      had failed. METHODS: Nine HBeAg and HBV-DNA seropositive patients received thymus
      humoral factor-gamma 2 alone for 2 months, thymus humoral factor-gamma 2 plus
      alpha-interferon for 2 months and finally alpha-interferon alone for 2 months.
      RESULTS: Treatment with thymus humoral factor-gamma 2 alone was not associated
      with any side effects. The interferon-induced lymphopenia was significantly less
      marked during the combined therapy in comparison to the previous course with
      interferon alone (mean reduction of lymphocyte counts 33.5 +/- 11.6% versus 56.3
      +/- 16.7%, respectively, p < 0.05). The combination of thymus humoral factor
      gamma 2 plus interferon showed a significantly more profound inhibition of serum
      HBV-DNA (mean reduction from the pretreatment level 90.6 +/- 13.3%) compared to
      the earlier monotherapy with interferon in the same patients (mean reduction 55.5
      +/- 34.7%, p < 0.01). As a result of the combined thymus humoral factor-gamma 2
      plus alpha-interferon regimen three out of nine patients became HBV-DNA negative
      and seroconverted to anti-HBe. Thymus humoral factor-gamma 2 appears to exert
      mainly a functional effect on T lymphocytes, as interleukin-2 production was
      increased in the majority of treated patients, whilst the expression of
      lymphocyte activation markers remained unchanged. CONCLUSIONS: These data suggest
      that thymus humoral factor-gamma 2 may be useful in a combined therapeutic
      approach in chronic HBV carriers.

PMID- 8530806
TI  - Mode of hepatitis C infection not associated with blood transfusion among chronic
      hemodialysis patients.
AB  - In a retrospective study carried out on about 730 patients with chronic renal
      failure who underwent ambulatory hemodialysis from January 1991 to June 1994, 49
      patients were found to have developed acute hepatitis C, as confirmed by
      seroconversion for anti-HCV antibodies without blood transfusion in the preceding
      6-month period. Epidemiological survey disclosed that two patients undergoing
      dialysis at consoles separated by one console developed acute hepatitis C in
      October 1992, and another three patients at adjacent consoles also developed
      acute hepatitis C within 2 weeks in April/May, 1993. It was found that some
      negligent nurses could have withdrawn needles from these patients one after
      another without changing gloves at the termination of the dialysis procedure.
      After reeducation of the staff members and introduction of a new type of adhesive
      pad to be placed on the needle wounds at the time of needle withdrawal, no new
      case of acute hepatitis C occurred for more than 1 year, suggesting nosocomial
      spread of HCV infection among hemodialysis patients in a mode that is preventable
      with very strict aseptic precautions.

PMID- 8530807
TI  - Frequency and significance of antibodies to histones in autoimmune hepatitis.
AB  - As part of ongoing studies to define the nature of anti-nuclear antibodies in
      autoimmune hepatitis and assess their clinical significance, we tested sera from
      65 patients who had previously been screened for reactivities to recombinant
      ribonucleoproteins (U1RNP-A and U1RNP-70K), ribonucleoprotein complexes (52K
      SSA/Ro and 60K SSA/Ro) and centromere (Cenp-B) for antibodies to histones by
      enzyme immunoassay. Twenty-three specimens were reactive to histones (35%).
      Eleven of the 23 seropositive specimens were also reactive to other nuclear
      antigens (48%); 12 specimens (52%) were reactive only to histone. Histone
      reactive sera did not have a characteristic pattern by indirect
      immunofluorescence. Patients with antibodies to histones were indistinguishable
      from other by age, gender, clinical and laboratory findings. HLA phenotype, or
      responses to corticosteroid therapy. Eighteen sera (28%) that had demonstrated
      nuclear reactivity by indirect immunofluorescence lacked reactivity to the five
      recombinant nuclear antigens and histones. We conclude that antibodies to
      histones are common in autoimmune hepatitis and that they are an important
      species associated with antinuclear reactivity. In some patients, they may be the
      only findings. Seropositive patients lack distinctive features or different
      outcomes after therapy. Reactivities against other nuclear antigens probably
      exist and remain undefined.

PMID- 8530808
TI  - Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment
      of patients with cirrhosis and grade 1-2 hepatic encephalopathy.
AB  - In 40 patients with cirrhosis on a dietary protein regimen of 1 g/kg b.w., we
      determined the effect on chronic hepatic encephalopathy of long-term
      administration of Enterococcus faecium (SF68) versus lactulose. The patients
      received one of the two treatments for three periods of 4 weeks, each separated
      by drug-free 2-week intervals. The efficacy of treatment was assessed by arterial
      blood ammonia concentration, mental status, number connection (Reitan's part A)
      test and flash-evoked visual potentials. At the end of the third period the
      reduction in both blood ammonia concentrations and Reitan's test times was more
      enhanced in patients on SF68 than in patients on lactulose. Furthermore, while
      patients on lactulose tended to return to basal values during drug-free
      intervals, responders in the SF68 group maintained improvement throughout the
      study. In conclusion, SF68 is at least as useful as lactulose for the chronic
      treatment of chronic hepatic encephalopathy; it has no adverse effects, and
      treatment can be interrupted for 2 weeks without losing the beneficial effects.

PMID- 8530809
TI  - Structure and expression of the cyclin A gene in human primary liver cancer.
      Correlation with flow cytometric parameters.
AB  - BACKGROUND/AIMS: The cyclin A gene plays an important role in both the S and G2-M
      phases of the cell cycle, and has been identified at a site of hepatitis B virus
      DNA integration in a human liver cancer. We analyzed tumorous and non-tumorous
      samples from patients with primary liver cancer to determine whether a) the
      cyclin A gene is rearranged in liver tumors and b) the cyclin A transcript level
      correlates with the percentage of proliferating cells. METHODS: Samples from 43
      patients were analyzed by Southern blot. Cyclin A RNA accumulation was evaluated
      in 18 cases by slot blot and correlated with the percentage of cells in S plus G2
      M phases defined by flow cytometry. RESULTS: No rearrangement of the cyclin A
      gene was found in tumorous compared to non-tumorous tissue. A very strong
      positive correlation was found between the cyclin A RNA level and the cumulative
      percentage of cells in S plus G2-M phases (r = 0.99; p < 0.0001). CONCLUSIONS:
      This in vivo study shows that the expression of cyclin A RNA correlates with the
      percentage of proliferating cells in primary liver cancer. Thus, cyclin A is a
      new potential liver tumor cell proliferation index.

PMID- 8530810
TI  - Transactivating function and expression of the x gene of hepatitis B virus.
AB  - BACKGROUND/AIMS: The x gene of hepatitis B virus encodes a transactivating factor
      of 154 amino acids, termed HBx, which stimulates transcription of multiple viral
      and cellular genes. The transactivating function is probably associated with a
      tumorigenic potential of HBx, since x gene sequences, encoding functional HBx,
      have been repeatedly found integrated into the genome of liver carcinoma cells.
      METHODS: To identify the transactivating domain of HBx, we constructed x gene
      plasmids encoding full length HBx or HBx fragments. We determined their
      transactivating function after cotransfection of cells, along with a plasmid that
      contains a reporter gene driven by the SV40 early promoter/enhancer region.
      RESULTS: Our results demonstrate that a 95-amino acid fragment of HBx,
      encompassing amino acids 49 to 143, contains all the elements that are required
      for the transactivating function. Within this fragment a sequence element,
      encompassing amino acids 107 to 130, which contains a relatively high number of
      amino acids with charged side chains, appears to be crucial for the stimulation
      of gene expression. The influence of deletion mutations on x mRNA steady-state
      levels and HBx stability was examined. In essence, stable RNA and protein were
      produced if at least codons 1-82 or 70-154 were present in the deletion plasmids.
      CONCLUSION: This finding strongly suggests that the deletion of functional
      domains between codons 49 and 143, but not an instability of RNA and/or protein,
      was critical for the loss of transactivation.

PMID- 8530811
TI  - Purification and characterization of cytoplasmic dynein of rabbit liver.
AB  - Cytoplasmic dynein is a microtubule-dependent motor protein, which plays a role
      in intracellular transport. However, there have been few studies regarding the
      role of cytoplasmic dynein in the liver. Purification of cytoplasmic dynein from
      rabbit liver took advantage of the affinity of microtubule-dependent motor
      proteins for microtubules. Purified dynein contained heavy chain (450 kDa),
      intermediate chain (75 kDa), light chains (45-58 kDa) and dynactin (150 kDa). The
      subunit composition was consistent with previously reported data on brain
      cytoplasmic dynein. Microtubules prepared from bovine brain were driven by
      purified cytoplasmic dynein from rabbit liver, and movements of microtubules were
      visualized by video-enhanced differential interference contrast microscopy. The
      mean velocity of the motile microtubules was 1.09 +/- 0.13 microns/s. Our study
      provides evidence of rapid intracellular transport in hepatocytes controlled by
      cytoplasmic dynein.

PMID- 8530812
TI  - Experimental atrophy/hypertrophy complex (AHC) of the liver: portal vein, but not
      bile duct obstruction, is the main driving force for the development of AHC in
      the rat.
AB  - BACKGROUND/AIMS: Patients with lobar or segmental impairment of bile flow or of
      portal venous blood flow frequently develop considerable atrophy of the area
      involved, followed by compensatory hypertrophy/hyperplasia of the non-affected
      parts. This configuration is termed atrophy/hypertrophy complex of the liver.
      METHODS: In order to analyze the relative contributions of bile duct and portal
      vein obstruction in the pathogenesis of atrophy/hypertrophy complex, we developed
      a rat model with selective bile duct and/or portal vein ligation of the anterior
      liver lobes, representing about two thirds of the liver mass. Evolution of total
      body weights and weights of the different liver lobes were determined, and
      morphometry and functional scintigraphy (hepatoiodida scanning) were performed
      immediately after ligation and at 30 h, 4, 8 and 28 days postoperatively.
      RESULTS: The major findings were: 28 days after biliary and/or portal ligation
      there was no difference between the body weights of all animals, all ligated
      animals having compensated an initial body weight loss. Total liver weight
      remained constant during the whole observation period, while atrophy of the
      anterior and hypertrophy/hyperplasia of the posterior lobes occurred. A
      significant atrophy/hypertrophy complex developed only after selective portal
      ligation, but not after selective biliary ligation. Morphometrically analyzed
      histologic changes after selective biliary ligation were reversible, whereas in
      portally ligated liver lobes a progressive parenchymal destruction and involution
      with subsequent impairment of hepatic function of the concerned lobe were
      observed. CONCLUSIONS: The present findings indicate that impairment of portal
      venous flow is the major driving force for the development of lobar atrophy in
      the rat and that atrophy/hypertrophy complex can be produced in a rodent model.

PMID- 8530813
TI  - Characterization of mechanisms causing hypoalbuminemia in rats with long-term
      bile duct ligation.
AB  - Albumin kinetics and albumin synthesis were studied in rats with chronic bile
      duct ligation and compared with pair-fed control rats. The plasma albumin
      concentration was significantly reduced in bile duct ligated rats as compared to
      control rats, averaging 35 +/- 1 vs 40 +/- 2 g/l after 2 weeks and 28 +/- 3 vs 38
      +/- 5 g/l after 4 weeks of bile duct ligation. Two weeks after bile duct
      ligation, the transcapillary escape rate of albumin was increased by 60% in bile
      duct ligated rats, whereas the plasma volume was unchanged. Albumin synthesis
      expressed as a fraction of total liver protein synthesis, as assessed by the
      'flooding' dose method using [3H]phenylalanine, was decreased by 46% in bile duct
      ligated rats. However, absolute albumin synthesis expressed per 100 g body weight
      was not different from control rats. Four weeks after bile duct ligation, the
      transcapillary escape rate of albumin was no longer different, whereas the plasma
      volume was increased by 38% in bile duct ligated rats. At this time point,
      albumin synthesis as a fraction of total liver protein synthesis was decreased by
      60% in bile duct ligated rats, and absolute albumin synthesis expressed per 100 g
      body weight averaged 80 +/- 8 vs 53 +/- 12 mg/(day x 100 g) in control and bile
      duct ligated rats (p < 0.05). The hepatic steady-state levels of albumin mRNA
      determined by Northern blot analysis were decreased in bile duct ligated rats at
      both 2 and 4 weeks after surgery. The studies suggest that reduced plasma albumin
      concentrations in bile duct ligated rats are caused by increased capillary
      permeability and lack of compensatory increase in albumin synthesis 2 weeks, and
      by increased plasma volume and decreased albumin synthesis 4 weeks after surgery.

PMID- 8530814
TI  - Prospective study of plasma fibronectin in fulminant hepatitis: association with
      infection and mortality.
AB  - BACKGROUND/AIMS: Plasma fibronectin is an opsonic glycoprotein, normally
      synthesized by the liver, which decreases subsequent to severe liver damage and
      low levels of which may contribute to reticuloendothelial system dysfunction by
      compromising opsonic activity. This may result in an increased frequency of
      infection and death. The present study was conducted to evaluate the association
      of plasma fibronectin activity with infection and mortality in patients with
      fulminant hepatic failure. METHODS: Plasma fibronectin was estimated serially in
      69 consecutive patients with fulminant hepatic failure, nine patients with
      uncomplicated acute viral hepatitis and 32 normal volunteers. RESULTS: Plasma
      fibronectin levels in patients with fulminant hepatic failure (85.6 +/- 75.8
      micrograms/ml) were significantly lower than in patients with uncomplicated acute
      viral hepatitis (295.5 +/- 88.5 micrograms/ml) and healthy volunteers (362.6 +/-
      69.2 micrograms/ml). Forty-nine (72%) patients with fulminant hepatic failure
      died. The initial values of fibronectin in fulminant hepatic failure did not
      correlate with mortality. Patients with fulminant hepatic failure who survived
      showed a progressive rise in the fibronectin levels compared to the absence of an
      increase in fibronectin levels in the non-survivors. The mortality in patients
      with fulminant hepatic failure with infection (24/27) was significantly higher (p
      < 0.05) compared to those without infection (25/42). Initial fibronectin levels
      in patients with infection (70.3 +/- 54.2 micrograms/ml) were significantly lower
      (p < 0.05) than in those without infection (92.3 +/- 64.4 micrograms/ml). We
      conclude that plasma fibronectin levels in patients with fulminant hepatic
      failure are decreased compared to healthy subjects and the absence of an increase
      in levels indicates a poor prognosis. Low levels of fibronectin are associated
      with an increased incidence of infection, which increases the mortality in these
      patients.

PMID- 8530815
TI  - The immuno-stimulant OK-432 enhances liver regeneration after 70% hepatectomy.
AB  - The effect of reticuloendothelial system activation on hepatic regeneration after
      70% hepatectomy was investigated. OK-432, a killed streptococcal preparation
      which increases reticuloendothelial system function, was administered to rats
      prior to 70% hepatectomy. Hepatic incorporation of 3H-thymidine 24 h after 70%
      hepatectomy was enhanced by OK-432 pretreatment. DNA synthesis was greater in
      pretreated than in control rats and correlated highly with reticuloendothelial
      system phagocytic activity prior to surgery. Methyl palmitate, which decreases
      reticuloendothelial system function, was administered to rats prior to 70%
      hepatectemy. Hepatic incorporation of 3H-thymidine 24 h after 70% hepatoctomy was
      significantly depressed by methylpalmitate-pretreatment. These data suggest that
      reticuloendothelial system plays a role in liver regeneration and that hepatocyte
      proliferation might be enhanced by protection from surgical stress and endotoxins
      with reticuloendothelial system stimulation by OK-432.

PMID- 8530816
TI  - Tamoxifen-associated steatohepatitis--report of three cases.
AB  - The authors describe three cases of tamoxifen-associated steatohepatitis, which
      resulted from a daily dosage of 20 mg used as the adjuvant treatment of breast
      carcinoma. Liver tests became normal after discontinuation of tamoxifen.

PMID- 8530817
TI  - Transplantation of hepatitis B immune lymphocytes as means for adoptive transfer
      of immunity to hepatitis B virus.

PMID- 8530819
TI  - Medicaid program designed to improve access.

PMID- 8530820
TI  - Medicaid managed care gets mixed reviews.

PMID- 8530818
TI  - AMA officer: put patient in driver's seat. Interview by Bob Carlson.

PMID- 8530821
TI  - Maintaining confidentiality of computerized medical records.
AB  - One of the most basic medical values is the sanctity of the doctor/patient
      relationship and the confidentiality of the communication between the physician
      and the patient. Another important medical tradition is the production and
      maintenance of an accurate medical record. In today's health care market, the
      needs of the payers, the providers and the patients have driven the development
      of the computerized patient record. the primary advantage of a computerized
      medical record is the ability to store vast amounts of information and handle the
      data more efficiently. Such speedy access to data can benefit patient care, but
      it also threatens the patient's privacy and right to confidentiality. Security of
      the computerized record poses more of a challenge than protecting the traditional
      paper chart. There currently is no comprehensive federal legislation dealing with
      the privacy of a citizen's electronic medical record. It may be necessary to
      sacrifice some individual privacy in order to receive the benefits of a
      computerized record. Risks to this confidentiality are many, but can be
      generally, but not totally, controlled. Acceptable responses to these threats
      combine technological and practical measures. It is the provider's responsibility
      to inform his patients of the limitations of security measures and to warn them
      of the potential threats to maintaining confidentiality of the medical record.

PMID- 8530822
TI  - Treatment and outcome of minimal stage breast cancer in a local hospital setting.

PMID- 8530823
TI  - Teamwork improves breast cancer management in the community.
AB  - The weekly breast cancer conference has clearly improved this community's ability
      to care for breast cancer patients. The range of issues has been broad. Some of
      the discussions are related to various aspects of surgical care, pathology issues
      such as specimen marking and evaluation, the use of prognostic indicators,
      adjuvant treatment, hormone replacement, bone marrow transplantation, post
      lumpectomy mammography, etc. The list is endless and expands every week. This
      conference format is very feasible in a community setting and has ongoing in
      depth benefits. Each host hospital designates one person to regularly coordinate
      preparation of the host hospital's conference. This ensures timely retrieval of
      all related diagnostic information for review by the radiologist and pathologist.
      Additionally, the case history is typed and available only on the morning of the
      conference.

PMID- 8530824
TI  - Museum to open exhibit on history of radiology.

PMID- 8530825
TI  - Hyperlipidemia in acute pancreatitis. Cause or epiphenomenon?
AB  - Whether hyperlipidemia is a pre-existing metabolic disorder or a consequence of
      acute pancreatitis is still debated. Mild to moderate elevation of serum
      triglyceride levels are likely to be an epiphenomenon of the pancreatic disease.
      A marked hyperchylomicronemia and hypertrygliceridemia would be needed to trigger
      acute pancreatitis; a relevant defect in the lipid catabolism and clearance
      should therefore pre-exist. The aim of the present study was to investigate
      whether patients with acute pancreatitis and marked hyperlipidemia have an
      impaired clearance capacity of exogenous lipids, which would define the
      hyperlipidemia as a preexistent abnormality and therefore a potential cause of
      the pancreatic disease. With this aim, the kinetics of the removal of exogenous
      triglycerides from the circulation have been analyzed. Twenty patients with acute
      pancreatitis have been studied. Ten of them suffered from an episode of acute
      pancreatitis with marked hyperlipidemia (serum triglyceride levels > 20 mmol/L).
      Four to six months after recovery from the pancreatitis, a two-stage infusion of
      Intralipid 20% was carried out and the fractional removal rate (K2) and the
      maximal clearance capacity (K1) of exogenous triglycerides were calculated. At
      low infusion rates a first order kinetics for removal was observed, whereas at
      high infusion rates a zero order kinetics was operating. All patients with a
      previous attack of normolipidemic acute pancreatitis had normal K2 and K1 values.
      Five patients with previous hyperlipidemic acute pancreatitis had an abnormally
      low clearance capacity of exogenous triglycerides, whereas the remaining five had
      normal removal values. The present study provides new information in the
      association between hyperlipidemia and acute pancreatitis by showing that even a
      marked elevation of serum lipid levels should not be invariably considered as the
      etiological factor of the pancreatic disease, even if other potential causes are
      not evident.

PMID- 8530826
TI  - Effect of neurotensin on pancreatic growth and pancreatic polyamine metabolism in
      rats.
AB  - The neuropeptide neurotensin is known to play a role in the regulation of
      exocrine pancreatic secretion, but actually there are conflicting results as to
      whether or not neurotensin exerts a trophic response on the pancreas and there
      are no data concerning its effect on pancreatic polyamine metabolism. In the
      present study, acute and long-term effects of various intraperitoneal dosages of
      neurotensin that resulted in mildly supraphysiological and even unphysiological
      high plasma concentrations of neurotensin were studied. Furthermore, neurotensin
      was simultaneously administered with cholecystokinin (1 microgram CCK-8/kg body
      wt ip every 8 h) for five days. The administration of neurotensin resulted in an
      acute significant decrease of pancreatic amylase and trypsinogen concentrations
      (p < 0.001), which indirectly confirms the potent effect of neurotensin on
      pancreatic exocrine secretion. In contrast to that, neither during the short-term
      study (100 micrograms neurotensin/kg body wt ip every 8 h for 2, 4, 6, 8, 16, and
      24 h) nor during the long-term study (1 microgram, 100 micrograms, or 200
      micrograms neurotensin/kg body wt ip three or eight times daily for 10 d) did
      neurotensin administration result in any increase of the various parameters of
      pancreatic growth and polyamine metabolism. Simultaneous administration of
      neurotensin and CCK failed to alter or further increase the known stimulatory
      effect of CCK on pancreatic polyamine metabolism and pancreatic growth after 5 d
      of treatment. These data indicate that neither alone nor in combination with
      cholecystokinin did various dosages of neurotensin exert any significant
      stimulation on pancreatic growth or the parameters of pancreatic polyamine
      metabolism.

PMID- 8530827
TI  - Toward an animal model of chronic pancreatitis. Pancreatobiliary secretion in
      hamsters on long-term treatment with chemical inducers of cytochromes P450.
AB  - There is currently no reproducible model of the painful and lithogenic disease,
      chronic pancreatitis. Its biphasic evolution, from acinar cell hyperplasia and
      hyperactivity toward effacement of enzyme as well as bicarbonate secretory
      parenchyma, would be rationalized if it was linked to induction of cytochrome
      P450 mono-oxygenases (CYP): the increased oxidant load from long-term CYP
      induction eventually erodes micronutrient antioxidant defenses to injure cells.
      This philosophy would also rationalize the reported hepatobiliary aberrations
      associated with the human disease, including increases in free radical oxidation
      products in bile. Accordingly, pancreatic and biliary secretions were studied in
      Syrian golden hamsters that were reared for 6 mo on low or high (16% corn oil)
      fat diets that were supplemented with a prototype inducer of CYP2 (200 ppm
      phenobarbitone) or CYP1 (100 ppm beta naphthoflavone) enzyme families, with or
      without a putative enzyme inhibitor (400 ppm cimetidine). The drugs did not alter
      the reduction in flow rate or bicarbonate concentration of pancreatic juice
      caused by the high fat diet alone, but, in contrast, evoked pancreatic protein
      hypersecretion in a number of animals. beta naphthoflavone, but not
      phenobarbitone, augmented the output of biliary lipid peroxidation products
      irrespective of dietary fat content, and cimetidine cotreatment with either
      inducer did the same. We conclude: (1) that drug modifiers of CYP magnify the
      deleterious pancreatobiliary effects of corn oil-enriched diets and draw them
      closer to those found in human chronic pancreatitis; (2) that these functional
      derangements are accompanied by pancreatic lipoatrophy; and (3) that long-term
      CYP induction does not, of its own, cause fibrosis or the ductal abnormalities
      that generally accompany loss of pancreatic acinar cells in the human disease
      and, also in contrast, the changes that are caused appear to be painless.

PMID- 8530828
TI  - Plasma amino acid consumption and pancreatic secretion during and after cerulein
      induced pancreatitis in rats.
AB  - The decrease in pancreatic exocrine secretion during the course of acute
      pancreatitis is a well-documented process. However, the mechanisms underlying
      this reduced pancreatic function are not fully understood. To analyze pancreatic
      protein synthesis and secretion during and after cerulein-induced pancreatitis,
      we performed the plasma amino acid consumption test on conscious rats. After
      stimulation with 1 microgram cerulein/kg/h sc for 1 h, the control group with
      intact pancreas exhibited a decrease in plasma amino acid by about 15%, and this
      decrease could be abolished by the administration of the specific CCK-receptor
      antagonist, loxiglumide. Protein and amylase secretion were augmented by cerulein
      to about 400% of control values. Upon supramaximal stimulation of the pancreas
      with cerulein (20 micrograms/kg/h sc for 5 h), we observed a profound decrease of
      pancreatic secretion, which was accompanied by a more prolonged and more
      pronounced decrease of plasma amino acids (25%). Two hours after cessation of the
      supramaximal stimulation of pancreatic secretion (to induce pancreatitis), the
      administration of 1 microgram/kg/h of cerulein for 1 h resulted in a further
      decrease of amino plasma acid level, whereas no stimulation of exocrine
      pancreatic secretion was observed. Eighteen hours later, repeated administration
      of 1 microgram/kg/h of cerulein was still able to induce amino acid decrease by
      20%, but again, no stimulation of exocrine pancreatic secretion was detectable.
      We conclude that, in the time course of acute cerulein-induced hyperstimulation,
      there might be an imbalance between synthesis of pancreatic enzymes (reflected by
      amino acid consumption) and the release of exocrine pancreatic secretion into the
      duodenum, which may be explained by leakage of proteolytic enzymes from damaged
      acinar cells into the extracellular space of the pancreas.

PMID- 8530830
TI  - Survival and morphology of isolated pancreatic acinar cells from rats with
      induced acute pancreatitis are not improved with anti-inflammatory drugs.
AB  - The influence from anti-inflammatory drugs on cellular damage of pancreatic
      acinar cells after induction of an acute pancreatitis (AP) in a rat model was
      investigated. Necrotizing pancreatitis was induced by retrograde instillation of
      trypsin solution in the pancreatic duct (group I). The severity of inflammation
      was determined using morphological and histological parameters 6, 24, and 48 h
      after induction of the necrotizing pancreatitis. After isolation of acinar cells,
      the degree of damage was measured by trypan blue exclusion--a parameter of
      membrane permeability--as well as accumulation of rhodamine 6G--a parameter of
      the mitochondrial membrane potential. In groups II-V, rats were treated with the
      anti-inflammatory drugs indomethacine, hydrocortisone, cimetidine, and
      acetylsalicylic acid (ASS) before induction of AP. There was no significant
      benefit from therapy in either group regarding cell membrane damage, cellular
      energy metabolism, or histology.

PMID- 8530829
TI  - Chronic oral administration of synthetic trypsin inhibitor camostate reduces
      amylase release from isolated rat pancreatic acini.
AB  - In the present study, we examined stimulus-secretion coupling in pancreatic acini
      prepared from rats given synthetic protease inhibitor camostate at a dose of 200
      mg/kg body wt by an orogastric tube once a day for 10 d. Camostate treatment
      significantly increased pancreatic weight, protein, DNA, and enzyme contents. In
      acini prepared from the camostate-treated rats, responsiveness to both CCK-8 and
      carbamylcholine was greatly decreased with no shift in the dose-response curves
      compared to control acini prepared from saline-treated rats. There were no major
      changes in the affinity for both high- and low-affinity sites of CCK receptors,
      but there was a significant reduction in the capacity of low-affinity site based
      on acinar protein. Responsiveness to secretin in the camostate-treated rat acini
      was also significantly reduced compared with that in the controls. However,
      amylase release from the camostate-treated rat acini in response to an increase
      in intracellular calcium levels induced by the calcium ionophores A23187 or to an
      increase in intracellular cyclic 3',5'-monophosphate (cyclic AMP) levels caused
      by 8 bromo cyclic AMP was not significantly different from the control rat acini,
      suggesting that both Ca(2+)-dependent tyrosine kinase and nucleotide-activated
      kinases are not impaired. On the other hand, the responsiveness to phorbol ester
      TPA, which stimulates amylase secretion via a calcium-independent cascade by
      activating protein kinase C directly, was reduced in the camostate-treated rat
      acini compared with the controls. These results suggest the possibilities that
      the reduced amylase secretion in the camostate-treated rats is owing to
      alterations in both the transmembrane signal transduction and the phosphorylation
      of regulatory proteins by the Ca(2+)-independent, protein kinase C-dependent
      mechanisms.

PMID- 8530831
TI  - Protective effect of 4-hydroxy-TEMPO, a low molecular weight superoxide dismutase
      mimic, on free radical toxicity in experimental pancreatitis.
AB  - Rats develop acute pancreatitis when infused iv for 3 h with cerulein (10
      micrograms/kg/h). Autopsies of the pancreas seen by light microscope show
      interstitial edema, acinar cells vacuolization, and leukocyte margination in
      pancreatic capillaries; under electron microscope, severe damage concerning
      mitochondrial and zymogen granules structures are apparent. Particularly,
      swelling of the mitochondria and disruption of mitochondrial cristae was observed
      as well as formation of large vacuoles arising from zymogen granules and liposome
      fusion. A significant increase of lipid hydroperoxide level in the pancreatic
      tissue was observed. The purpose of this study was to evaluate the effect of 4
      hydroxy-TEMPO--a low-mol-wt superoxide dismutase mimic--in a rat cerulein model
      of acute pancreatitis, with the expectation that free radical mediated
      hydroperoxide formation and tissue damage may be reduced significantly. Twenty
      one male Wistar rats were divided into three groups: Group 1 (n = 5) served as a
      control and was infused iv for 3 h with physiologic saline; Group 2 (n = 8) was
      infused i.v. for 3 h with cerulein 10 micrograms/kg/h; and Group 3 (n = 8)
      infused i.v. both with cerulein and 4-hydroxy-TEMPO 22.6 mg/kg/h. Pancreatic
      tissue damage was quantified by measuring lipid hydroperoxide (LOOH) level, the
      weight of the organ, and by light and electron microscopic examination. 4-hydroxy
      TEMPO penetration across cellular membrane barriers was quantified by ESR
      spectrometric measurements of 4-hydroxy-TEMPO concentration in pancreatic tissue
      samples and pancreatic juice as well. Administering 4-hydroxy-TEMPO to rats
      resulted in preventing both lipid hydroperoxide formation and severe
      morphological damage. 4-hydroxy-TEMPO crossed cellular membrane barriers and was
      excreted to pancreatic juice. Infusion of 4-hydroxy-TEMPO appears to prevent
      pancreatic injury caused by free radicals in experimental cerulein pancreatitis.

PMID- 8530832
TI  - Solitary true cyst of the pancreas in adults. Report of three cases and review of
      the literature.
AB  - Solitary true cysts of the pancreas are extremely rare: to date, only eight cases
      have been reported in the English literature, four of which had clinical
      significance. An additional three cases of solitary true cysts of the pancreas
      are presented. One patient was incidentally found at operation, performed for
      other disease, to have a cystic lesion in the body of the pancreas; the other two
      patients experienced abdominal pain and nausea. Abdominal US, CT, and MR showed a
      unilocular cyst in the body and tail of the pancreas. In both cases, preoperative
      diagnosis of pancreatic cystic neoplasm was made. Two patients underwent excision
      of the mass and one distal pancreatectomy. Analysis of the cyst fluid revealed
      high CA 19-9 levels in two and CA 125 levels in one case. All cysts were lined by
      cuboidal epithelium, without morphological alterations. Preoperative differential
      diagnosis with the most common cystic pancreatic lesions (inflammatory or
      neoplastic) is difficult.

PMID- 8530833
TI  - Mixed pleomorphic-osteoclast-like tumor of the pancreas. Light microscopical,
      immunohistochemical, and molecular biological studies.
AB  - The morphological, immunohistochemical, and molecular biological features of a
      case of giant cell tumor of the pancreas are described. This neoplasm showed
      mononuclear and multinucleated tumor giant cells as well as numerous osteoclast
      like cells with multiple foci of osteoid-osseous metaplasia. The pleomorphic and
      osteoclastic giant cells displayed extensive homologies in their
      immunohistochemical profiles. Neither the pleomorphic nor osteoclast-like portion
      of the tumor showed neither c-Ki-ras nor p53 mutation and did not express the
      mutated p53 protein. The results suggest that the pleomorphic and osteoclast-like
      components are histogenetically related and that this rare neoplasm originates
      from a precursor cell capable of differentiating along divergent cell type.

PMID- 8530835
TI  - Immunohistochemical staining for type IV collagen and laminin in the stroma of
      human pancreatic cancer.
AB  - Fourteen human pancreatic cancer, six normal pancreatic, and four alcoholic
      chronic pancreatitis tissue samples were examined by immunohistochemistry with
      antitype IV collagen and antilaminin monoclonal antibodies (MAb). The basement
      membranes of acinar, ductal, and endothelial cells from all of the normal
      pancreatic and alcoholic chronic pancreatitis tissue samples were continuously
      immunostained, but the stroma was negatively immunostained by both antibodies. On
      the other hand, all 14 pancreatic cancer tissues showed irregular immunostaining
      on the basement membranes surrounding cancer cells, and positive fibrillar
      immunostaining for type IV collagen in the stroma of the carcinomatous
      parenchyma. Six of the 14 pancreatic cancer tissue samples also showed positive
      immunostaining for laminin in the stroma. The stromal type IV collagen with or
      without laminin in human pancreatic cancer tissues may have originated from
      basement membranes degraded through cancer invasion and proliferation.

PMID- 8530836
TI  - [Thoracoscopic debridement for acute empyema].
AB  - Thoracoscopic debridement for acute empyema was successfully performed in three
      patients who were refractory to closed drainage, irrigation and antibiotic
      therapy. In two patients anaerobic organisms were isolated from the pus. None of
      the patients had bronchopleural fistula. All patients were relieved of fever
      promptly after surgery. Operative invasion was minimal, and postoperative lung
      function was well maintained one month after the operation. If empyema is in the
      fibrinopurulent phase and does not respond to pleural drainage, thoracoscopic
      debridement may be indicated before more aggressive therapy.

PMID- 8530834
TI  - Development and regulation of porcine pancreatic function.
AB  - A surgical and experimental procedure was developed to enable the collection of
      pure and inactivated pancreatic juice during the growth of the pig. Studies have
      shown that, during the suckling period, both the basal and the secretory
      responses to suckling are low, if present at all. After weaning, basal levels of
      the total exocrine secretion, total protein, amylase, and trypsin, respectively,
      increase slightly, while the postprandial levels of total protein, amylase,
      trypsin, lipase, colipase, and carboxylester lipase, respectively, increase
      markedly. The pancreatic juice enzyme composition changes qualitatively and the
      antibacterial activity of the pancreatic juice also significantly increases.
      Piglet age appeared to be of minor importance, since weaning at either 4 or 6 wk
      of age gave the same results. Secretin and CCK administered together in
      supraphysiological doses only significantly affect exocrine function from 3-4 wk
      of age. However, CCK may also affect the exocrine pancreas indirectly via
      reflexes initiated intraduodenally. Milk consumption in the suckling pig leads to
      a postprandial increase in glucose levels but not insulin. Milk appears to be
      able to regulate the exocrine pancreas to produce only the amount and type of
      enzymes required for digestion. Thus, milk components or digestive products may
      affect pancreas function regulation. Studies show that enterostatin, the
      procolipase activation peptide, may inhibit pancreatic secretion mediated
      indirectly through the GI tract. Pancreastatin, an endocrine peptide, inhibits
      both insulin secretion and protein and trypsin secretion to pancreatic juice. In
      hypoinsulinemic (alloxan+streptozotocin diabetes) pigs (15-20 kg), no
      postprandial pancreatic juice response is seen, although CCK 33 + secretin can
      stimulate pancreatic secretion. Hypoinsulinemic pigs have a reduced capacity for
      glucose tissue utilization, suggesting that tissue metabolism and exocrine
      pancreas secretion are related.

PMID- 8530837
TI  - [Renal autotransplantation for dissecting aneurysm].
AB  - Out of twenty-five patients operated on for dissecting aneurysm in our
      institution since January 1991, four patients had autotransplantation of the
      kidney. The renal autotransplantation and the segmental replacement of the
      descending aorta with the prosthesis were done at the same time in three of them,
      and segmental replacement of the distal aortic arch was followed by
      autotransplantation because of the postoperative acute renal failure in the other
      one. Postoperative renal function of simultaneously operated patients was good
      whereas the patient who had been treated by two-staged operation needed
      hemodialysis for two weeks after the autotransplantation. Postoperative
      scintigraphy showed fully recovered function of the autotransplanted kidneys with
      enlargement. CT scan showed that the false lumen of the dissecting aorta was
      reduced in size with increased intraluminal clot formation. Renal
      autotransplantation with entry closure is easy and safe technique and assures
      successful operative results for the dissecting aneurysm, restoring impaired
      renal blood flow.

PMID- 8530838
TI  - [Clinical experience of the combined use of polyglycolide non-woven felt with
      fibrin glue to prevent postoperative pulmonary fistula].
AB  - Felt prepared from polyglycolide (PGA) polymer fibers was pasted with fibrin glue
      for prevention of postoperative pulmonary fistula, and its effects were
      evaluated. The subjects were 90 patients who underwent thoracotomy and were
      expected to develop air leakage between March 1990 and the end of 1993. The felt
      sheet was simply pasted in position in 67 patients, applied and fixed by suturing
      in 7, and sutured and pasted in 16. The duration of air leakage in the three
      groups were 4.6 +/- 4.1, 3.9 +/- 4.9, and 3.2 +/- 3.8 days, respectively.
      According to the surgical procedure employed, the duration of air leakage was 5.0
      +/- 4.0 days in 41 patients who underwent pulmonary lobectomy, 5.0 +/- 4.3 days
      in 5 patients who underwent segmentectomym, 2.6 +/- 3.1 days in 26 cases who
      underwent partial pneumonectomy, and 4.9 +/- 4.0 days in the 14 cases who
      underwent bulla resection. In terms of disease, the leakage time was 4.6 +/- 4.2
      days in patients with emphysema, 0.6 +/- 1.2 days in those with diffuse pulmonary
      fibrosis, 0.7 +/- 0.9 days in those with Infectious disease, 4.8 +/- 4.2 in those
      with lung cancer, 1.5 +/- 1.5 days in those with benign lung tumor, and 3.8 +/-
      2.7 days in those with metastatic lung tumors. The procedure had no side-effect
      on liver or kidney function. No infection was observed even after decortication
      for empyema. The use of felt prevented excessive shrinking of the lung due to
      over-suturing. Therefore, intraoperative application of a PGA felt sheet was
      considered to be an effective method for prevention of pulmonary fistula.

PMID- 8530839
TI  - [Cardiac operation of the cases associated with malignant tumor].
AB  - Twelve cases of malignant tumor (mean age 64 years) underwent the cardiac
      operation. The procedure of cardiac operations were 10 coronary artery bypass
      grafting and 2 mitral valve replacement. The detail of malignant tumors were 4
      gastric cancer, 3 colon cancer, 3 lung cancer, 1 esophageal cancer and 1 lip
      cancer. The cardiac operations followed the operations of malignant tumor in 4
      cases and the cardiac operations were followed by the operations of malignant
      tumor in 7 cases. The former cases did not recur the tumor from 10 to 30 months
      follow up period. The all latter cases survived except 1 case from 1 month to 21
      months. Our management for the cases associated with malignant tumor and cardiac
      diseases as next. We perform the cardiac operation for the case whose life
      expectancy is longer than 1 year. We perform the cardiac operation before the
      operation of malignant tumor. We perform the operation for malignant tumor as
      soon as the patient had recovered from the cardiac operation. We would not
      perform any adjuvant therapy before completion of the operation for the heart and
      tumor.

PMID- 8530840
TI  - [Comparison of long-term clinical results of the three models of the Bjork-Shiley
      valve prosthesis and the Omnicarbon valve prosthesis].
AB  - A multi-institutional cooperative study, that was a comparison of long-term
      results of the replacement of the four models of the oblique disc valve
      prosthesis which had been implanted on aortic and mitral position alone or double
      from December 1976 to September 1992 in the eight national hospitals in Japan was
      performed. Seven hundred and thirty-four patients and 765 prostheses that
      consisted of 582 patients and 610 prostheses of the Bjork-Shiley (BS) valve,
      including 326 patients of the Spherical disc (SP) valve (49 aortic, 259 mitral,
      and 18 double aortic-mitral), 103 patients of the Convexoconcave disc (CC) valve
      (45, 51, 7) and 153 patients of the Monostrut (MS) valve (101, 49, 3), and of 152
      patients (71, 78, 3) and 155 prostheses of the Omnicarbon (OC) valve were
      compared with their mortality and morbidity in every valve position respectively
      according to the approval by STS-guideline. The MS valve and the OC valve showed
      0% to 11.3% of operative mortality, 0.3%/py to 1.8%/py of valve related
      mortality, 85.5% +/- 5.6% to 98.4% +/- 1.6% of actuarial survival rate at 10
      years, and 58.5% +/- 6.4% to 82.7% +/- 5.7% of actuarial free rate of all
      mortality and morbidity at 10 years in every valve position. Structural
      deteriorations occurred in two patients of the CC valve in the mitral position
      only, and its rate of all valve positions showed 0.04%/py. Significant
      differences were seen in actuarial survival rate at 10 years after aortic valve
      replacement, and in operative mortality rate, improved degree of NYHA class,
      structural deterioration rate and actuarial free rate of all mortality and
      morbidity after mitral valve replacement between the group of the MS and OC valve
      and the group of the SP and CC valve. Therefore the MS valve or the OC valve
      should be selected to implant rather than the SP valve or the CC valve, and the
      patient who had been implanted with the CC valve should be treated considering
      valve position, valve position, valve size, age and activity of the patient and
      the manufactured date of the prosthesis.

PMID- 8530841
TI  - [Noninvasive detection of the limitation of simple cold storage of the heart by
      myocardial electrical impedance].
AB  - The purpose of this study was to determine if graft viability during simple cold
      storage can be monitored from alteration of myocardial electrical impedance.
      Twelve anesthetized dogs were underwent rapid cardiac extripation and were placed
      in simple cold storage. They were divided into two groups according to preserved
      solution. Group S was preserved in 12 hours in saline. Group U was preserved in
      24 hours in the University of Wisconsin (UW) solution. Myocardial electrical
      impedance was measured serially by use of a LCR meter and analyzed the changes of
      myocardial resistivity during preservation. Myocardial specimens were taken for
      myocardial ATP measurement with high-performance liquid chromatography and for
      water content in two groups. Moreover in order to predict the cardiac function
      after transplantation in two groups, heterotopic cardiac transplantation in the
      neck was performed in mongrel dogs and left ventricular (LV) Emax was measured.
      Myocardial resistivity increased significantly until 5.5 hours in group S, 13
      hours in group U. ATP remained above 50% at 5.5 hours in Group S, 13.7 hours in
      Group U. Resistivity increase rate was over 0.1 omega cm/min in the period ATP
      remained above 50%. Myocardial water content increased during preservation in
      group S, but did not in group U. There was no relationship between the increase
      of resistivity and myocardial water content. LVEmax at 120 min after reperfusion
      was over 90% of preischemic value in 4 hour preserved heart in saline and 12 hour
      preserved heart in UW. Measurement of myocardial resistivity during simple cold
      storage may be feasivle as a monitor of graft viability.

PMID- 8530842
TI  - [The effectiveness of perfluorotributylamine/pluronic F-68 stem-emulsion (FC43se)
      against xenograft rejection in the guinea pig-to-rat model].
AB  - The administration of perfluorotributylamine/pluronic F-68 stem-emulsion
      (FC43se), a fluorine compound emulsion, to a rodent discordant xeno
      transplantation (dXT) model led to the discovery of the inhibitory effect of this
      compound against hyperacute rejection (HAR). When a guinea pig heart was
      transplanted to a rat administered with FC43se (10 microliters/g body weight),
      rhythmic beating was maintained for 1110 +/- 111.1 min (mean +/- SD; n = 8)
      whereas the untreated heart continued to beat for 15.5 +/- 6.6 min (mean +/- SD;
      n = 8). After 720 min of re-beating; pathologic changes observed in the untreated
      group, such as multiple thrombosis in the coronary vessels, were not observed in
      the FC43se-administered group by light and electron microscopic examination, and
      endothelial cells were well preserved. On the other hand, scattered necroses of
      the myocardium were observed and lymphocytic infiltration was demonstrated in the
      interstitium. We concluded that FC43se possessed a HAR inhibitory effect by
      inhibiting thrombus formation in the xeno-graft heart. Using this model, we
      speculated that action in the vessels of the graft heart (intravascular HAR)
      caused thrombus formation in the vessels. On the other hand, extravascular HAR
      causes myocardial necrosis more slowly, not resulting in cardiac arrest in the
      short term.

PMID- 8530843
TI  - [Coronary revascularization with arterial graft alone by normothermic
      cardiopulmonary bypass and warm blood cardioplegia].
AB  - We studied the effects of Calafiore technique that is intermittent (every 15
      minutes) antegrade warm blood cardioplegia oxygenated and included high potassium
      solution with normothermic cardiopulmonary bypass. From September 1994 to
      February 1995, 20 patients having continuously elective coronary artery bypass
      grafting with arterial conduits alone were randomized to traditional intermittent
      cold crystalloid cardioplegia and slight hypothermic cardiopulmonary bypass (cold
      group) or warm heart surgery by Calafiore technique (warm group). Preoperative
      variables were similar to both groups, as were the intraoperative variables of
      number of coronary grafts, aortic cross-clamp time, and cardiopulmonary bypass
      time. Warm group had more rapidly spontaneous defibrillation at cross-clamp
      removal than cold group. CK on one postoperative day was lower than cold group.
      Warm group had good results as concern postoperative blood loss volume, intubated
      time, and change of base excess. Events of PMI (cold, 2 and warm, 0) and need of
      an intraaortic balloon pump (cold, 2 and warm, 0) were significantly lower in the
      warm group. We suspected the possibility of vasospasm was lower in the warm
      group. We concluded warm heart surgery (Calafiore technique) was a best technique
      for CABG with arterial conduits.

PMID- 8530844
TI  - [Double valve replacement with mechanical prostheses--an operative results].
AB  - From January 1980 to December 1993, sixty eight patients underwent double valve
      replacement with mechanical prostheses. There were forty males and twenty-eight
      females with a mean age of 49.6 years (ranging from 30 to 68 years). They were
      classified 10 of NYHA class IV, 28 of class III. Twelve patients had previous
      cardiac operation. TR was identified in 20 patients. DVR was performed in 53
      patients, DVR + TVR in one, DVR + TAP in 13. Twenty-two had St. Jude Medical
      (SJM) prostheses and 46 had Bjork-Shiley (BS) prostheses. Early death before 30
      postoperative days occurred in 6 patients (8.8%). MOF was the most frequent cause
      for early death. The risk factors for early death were the NYHA class IV,
      infective endocarditis, longer duration of cardiopulmonary bypass, necessity of
      postoperative IABP support. Other factors such as emergency operation, previous
      operation, tricuspid valve surgery, duration of aortic cross clamp time were not
      the predictors for early death. Cumulative follow-up was 284.0 patient years
      (PY). The rate of late survival was 74.1% (40 patients). Linearized rates of
      thromboembolism (TE), prosthetic valve endocarditis (PVE), hemolysis (H),
      reoperation (RO) were 2.8%/PY, 0.7%/PY, 0.4%/PY, 1.1/PY respectively. The free
      rates from TE, PVE, H, RO at nine years were 75.6%, 96.2%, 93.1%, and 89.8%,
      respectively. The cumulative survival rates at 14 years were 53.2% in over-all
      patients, and 64.3% in hospital survivors. We conclude that the early surgery is
      recommended for the patients with multiple valvular heart disease. The late
      outcomes of DVR with SJM or BS mechanical prosthesis is an acceptable one.

PMID- 8530845
TI  - [Clinical significance of selective cerebral perfusion with cold blood on the
      brain protection].
AB  - In 42 patients with thoracic aortic disease, a selective cerebral perfusion with
      16 degrees C cold blood was applied for the brain protection during the repair of
      the thoracic aorta. The surgical repair consisted of the replacement of the
      ascending aorta (9 cases), the ascending aorta and aortic arch (12 cases), the
      aortic arch (18 cases), and the aortic arch and descending aorta (3 cases).
      Twenty-two patients of them (52%) required emergency surgery and four patients
      died due to postoperative complications including visceral organ ischemia (2
      cases) and multiple organ failure (2 cases). The mortality rate of this group was
      18.2% (4/22 cases). In elective surgical classes, one patient died due to
      intraoperative coronary embolism. The mortality rate of this group was 5.0% (1/20
      cases). No postoperative obvious brain defect was observed except one old patient
      (85-year-old female) with ruptured aortic arch who already had the brain
      infarction preoperatively. She died due to multiple organ failure with
      unconsciousness. Other patients including the patients with long cerebral
      perfusion (> 180 min) recovered well and returned to normal daily life. The
      selective cerebral perfusion with cold blood was easy to prepare and demonstrated
      the superb efficacy of brain protection in the patient.

PMID- 8530846
TI  - [Surgical treatment of acute aortic dissections--a clinical study using a ringed
      intraluminal graft].
AB  - From 1984 to 1994, surgery was performed using a ringed intraluminal graft (RIG)
      in 75 patients with acute aortic dissection (DeBakey's type I in 37 cases, type
      II in 10 cases and type III in 28 cases). The operative death rate was 24% for
      type I, 30% for type II and 21% for type III. The average time from onset to
      surgery was short (47 +/- 67 hours for type I, 34 +/- 36 hours for type II and 47
      +/- 77 hours for type III). The outcome of these cases indicated that this
      technique was effective for saving the lives of patients in the acute early stage
      of aortic dissection. No characteristic complications developed after this
      surgery. The postoperative course of patients was followed by using CT scans,
      MRI, angiography. No patients developed aneurysmal formation in the ligated area
      or dislocation of the RIG. There were no deaths directly attributable to the RIG.
      Patients who were autopsied in the late postoperative period showed no aneurysm
      of the ligated area or necrosis of the aortic wall. In conclusion, RIG surgery
      effectively saved the life of patients with acute aortic dissection and the RIG
      could be used as prosthetic graft for long-term periods.

PMID- 8530847
TI  - [Mitral valve repair for mitral regurgitation--technical contrivance and its
      further application].
AB  - To evaluate the mitral reconstructive technique from the pathological and
      surgical points of view, 33 consecutive cases were analyzed. Eighteen patients
      (54.5%) were men, and the mean age was 40.9 +/- 19.8 (range 5 to 72 years). Ten
      patients (30.3%) had atrial fibrillation. The causes of mitral regurgitation were
      torn chordae tendinae in 17, elongated choradae tendinae in 14, annular
      dilatation in 8, papillary muscle dysfunction in 2, and congenital cleft in 4.
      The mitral regurgitation was due to prolapse of the anterior leaflet in 16,
      prolapse of the posterior leaflet in 10, and prolapse of both leaflets in 5.
      Resection and reconstruction of the leaflet was performed on anterior leaflet in
      15, and on posterior leaflet in 15. The anterior mitral cleft was sutured in 3.
      The newly contrived wrapping and shortening chordoplasty was performed on
      anterior leaflet in 6, on posterior leaflet in 3, and on both leaflets in 2. Two
      patients had replacement of artificial chordae tendinae with EPTFE suture.
      Commissuroplasty was performed at anterolateral commissure in 5, at posteromedian
      commissure in 15, and at both commissures in 5. Thirty patients with dilated
      annulus underwent ring annuloplasty by Carpentier ring. There was no hospital
      death. Two patients required mitral valve replacement for redeveloping mitral
      regurgitation 2 weeks and one year after initial operation. All patients were in
      NYHA functional class I after surgery. The Doppler echo cardiographic study
      revealed no mitral regurgitation in 27, mild or trivial in 3, and moderate in 3.
      LVEDVI and LVESVI significantly decreased, and left ventricular volume overload
      was markedly reduced.

PMID- 8530849
TI  - [Fontan procedure after pulmonary artery banding--surgical results and new
      anatomical repair for tricuspid atresia].
AB  - We examined our surgical experiences to determine the appropriate condition of
      pulmonary artery banding (PAB) for the Fontan procedure. From 1974 through 1992,
      thirteen patients underwent Fontan procedure following PAB at Tokyo Women's
      Medical College. Of these 6 had tricuspid atresia (TA), 5 had single ventricle,
      or 2 had other complex malformations. PAB was performed at the age of 1 to 14
      months (mean 2.5 months). With monitoring pulmonary artery (PA) pressure and
      systemic arterial oxygen tension (PaO2), PA mean pressure decreased 43.6 to 18.8
      mmHg and PA circumferences at the banding site decreased from 53.5 to 26.0 mm
      after PAB. This degree of PAB was tighter compared with the value estimated by
      Trusler's formula (27.9 mm) in most patients. After PAB, 5 patients required 8
      additional palliative surgery including 3 systemic to pulmonary shunt, 3
      rebanding, 1 palliative RVOTR to promote development of pulmonary vascular bed
      and 1 atrial septectomy to prevent pulmonary hypertension. Hemodynamic data
      before Fontan operation showed a tendency of higher PA pressure (17.5 vs 31.5
      mmHg), and pulmonary vascular resistance (2.4 vs 5.5 Wood Unit) in non-survivors
      than in survivors. For patients with tricuspid atresia and high pulmonary
      vascular resistance, a new operation "Anatomical Repair" utilizing hypoplastic
      right ventricle with the translocation of pulmonary or aortic valve in tricuspid
      position was developed and successfully applied in three patients. In conclusion,
      initial tight PAB during early infancy and often repeated palliative surgery for
      development of adequate pulmonary vascular bed is the most important for
      maximizing the chance of subsequent successful Fontan procedure.

PMID- 8530848
TI  - [Results of coronary artery bypass grafting in dialysis patients].
AB  - To determine the short- and medium-term results of coronary artery bypass
      grafting (CABG) in dialysis patients, we analyzed a group of 14 patients with
      chronic renal failure who underwent CABG between May 1990 and October 1994. Two
      patients had concomitant valve repair for mitral regurgitation. Hospital
      mortality was 14% (2 out of 14). These two patients died of ileus due to ischemic
      colitis and agranulocytosis respectively. There was one late death from stroke.
      The four significant postoperative complications (morbidity 29%) were composed of
      two sternal dehiscence, one cardiac tamponade because of bleeding, and one
      perioperative myocardial infarction. Graft patency rate was 97% (34 out of 35 in
      13 patients) within one month. Actuarial survival was 86% at one 1 to 3 years,
      and 43% at 3 and a half years. This rate is not significantly different from all
      dialysis patients, but night be better than dialysis patients with coronary
      artery disease who had not undergone CABG in the previous reports. Left
      ventricular size is larger in patients who died or who had significant
      complications in hospital than in patients with uneventful postoperative course.
      Cardiac arrest time, cardiopulmonary bypass time, chest tube output, and the
      amount of transfusion might be also related to mortality and morbidity though
      statistically not significant.

PMID- 8530851
TI  - [Experimental application of synchronized coronary sinus retroperfusion (SCSR)
      and left heart bypass (LHB) for severe cardiogenic shock].
AB  - In order to evaluate the efficacies of concomitant use of left heart bypass (LHB)
      and synchronized coronary sinus retroperfusion (SCSR) for ischemic cardiogenic
      shock refractory to conventional mechanical circulatory assist such as intra
      aortic balloon pumping (IABP), experimental comparison studies were made in
      swine. The acute myocardial infarction model was made by left anterior descending
      coronary artery (LAD) ligation method. LHB was performed by centrifugal pump
      (BioMedicus BP-80), supporting flows of half cardiac output. SCSR catheter was
      inserted into coronary sinus (CS) through external jugular vein. Then arterial
      blood was pumped from femoral artery to CS with flow of 60 to 70 ml/min which was
      synchronized to electrocardiogram (ECG). These animals were supported by only
      SCSR or LHB, and SCSR + LHB, comparing each cardiac performances, infarcted areas
      and coronary flow. Infarcted areas were evaluated by epicardial mapping ECG.
      Coronary blood flow and velocity were analyzed by electromagnetic flow meter and
      ultrasonic pulse doppler velocimeter respectively. In LHB group, coronary blood
      flow and velocity were increased because of elevation of mean aortic pressure. In
      addition, LVdp/dt, LVEDP were decreased, indicating left ventricular
      decompression. However, the infarcted area was slightly reduced. In contrast, it
      was remarkably reduced by SCSR, and cardiac function recovered gradually from
      cardiogenic shock. In SCSR + LHB group, the ischemic area was significantly
      reduced and their hearts completely recovered from cardiogenic shock,
      demonstrating the good supply and demand balance of myocardial oxygen. The
      systolic reverse LAD flow and velocity which was increased due to cardiogenic
      shock, was remarkably reduced. These results suggested this concomitant new
      application is suitable for recovering from cardiogenic shock due to AMI which is
      not able to apply antegrade coronary perfusion.

PMID- 8530850
TI  - [Experimental evaluation of a new gelatin-impregnated woven Dacron vascular
      prosthesis (CL301)].
AB  - We investigated the biological response and biodegradation of CL301, a presealed
      woven Dacron prosthesis (UBE woven) with glutaraldehyde stabilized gelatin. The
      sealant does not affect its handling characteristics because of the glycerin
      treatment. The total content of endotoxin in the CL301 was 5.3 +/- 0.5 pg/mg of
      sealant material (1.7 +/- 0.2 pg/cm2), which was 1/5 and 1/6 of that found in
      Hemashield and Gelseal, respectively. The pyrogen test was negative and the
      content was estimated below the minimum pyrogenic doses for thoracic aortic
      surgery. Five cm-long grafts with a diameter of 10 mm were implanted into the
      descending thoracic aorta of dogs weighing 10-16 kg. These grafts were retrieved
      2 hours, 7, 10 days, 5, 8 and 10 weeks after implantation. Thrombus-free surfaces
      were 28%, 77%, at 5 and 10 weeks and there was no excessive inflammatory response
      to the sealant. The total, and the effective sealant remaining were 80.6%, 56.5%
      at 5 weeks, 60.8%, 38.3% at 10 weeks, respectively. The sealant was removed more
      rapidly from the inner surface than from the outer. In half of the graft area,
      the sealant was removed or detached from the Dacron surface 5 weeks after
      implantation, indicating that delayed resorption of the sealant substantially did
      not affect the healing process. We conclude that because of the harmless amount
      of endotoxin and effective sealing for 5 weeks, followed by an acceptable healing
      process experimentally, CL301 is the presealed Dacron graft of choice for
      thoracic aortic surgery.

PMID- 8530852
TI  - [Reoperation for coarctation of the aorta and interrupted aortic arch].
AB  - This report presented four patients who underwent surgery for restenosis after
      repair of coarctation of the aorta (CoA) or interrupted aortic arch (IAA) at our
      institution between January 1980 and October 1994. Case #1 underwent primary
      repair for IAA, VSD, and PDA consisting of aortic arch reconstruction using a
      EPTFE (expanded polytetrafluoroethylene) graft of 10 mm in diameter at the age of
      four years. After 17 years, pressure gradient of 58 mmHg between the ascending
      aorta and the descending aorta prompted the reoperation. Case #2 underwent
      primary repair for CoA, VSD, and PDA consisting of a bypass between the ascending
      aorta and the descending aorta with an EPTFE graft of 11 mm in diameter at the
      age of three years. After 13 years, he had reoperation because of pressure
      gradient of 64 mmHg. Case #3 had pressure gradient of 20 mmHg between the upper
      and lower limb at the hospital discharge following patch angioplasty for CoA at
      five years of age. He underwent unsuccessful percutaneous transluminal balloon
      angioplasty at age 12 and had reoperation at age 15. Case #4 underwent subclavian
      flap angioplasty as the first stage operation for CoA, VSD, and PDA at 1 month
      after birth. About 9 months after the initial operation, the pressure gradient
      between the upper and lower limb had reached 40 to 50 mmHg, and the patient had
      reoperation at the age of 1 year. The reoperation method for cases #1, #2 and #3
      consisted of bypass grafting from the left subclavian artery to the descending
      aorta under a simple cross clamping of the thoracic aorta.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8530853
TI  - [Surgical results of aortitis syndrome (Takayasu disease) combined with
      annuloaortic ectasia].
AB  - From March 1973 to December 1994, 8 patients (2 males and 6 females) aged 34.4 +/
      7.8 years, underwent composite graft replacement (CGR) for aortitis syndrome
      combined with annuloaortic ectasia (AAE) in our institute. Five patients showed
      active aortitis syndrome and steroid therapy was administrated to 2 of them. The
      mean value of the C-reactive protein (CRP) was 1.6 +/- 1.8 before the operation.
      The maximum diameter of the ascending aorta was 67.1 +/- 10.3 mm (range 53 to 85
      mm). Stenosis and/or ectasia of the neck vessels were recognized in 5 cases, as
      well as the coronary artery in 2 cases. Isolated CGR was performed in 6 cases,
      and combined with single CABG to LAD in 1 case and with total arch replacement in
      1 case. The enlarged ascending aorta was replaced with main graft using the
      exclusion method and interposed grafts for coronary arteries were sutured with
      pledgetted mattress sutures all around the coronary ostia. In patients with
      stenosis of neck vessels, oxygen saturation of the jugular vein was monitored
      during extracorporeal circulation for surveillance of cerebral ischemia. There
      was 1 early death due to pulmonary failure. Seven cases survived without any
      complications during 4-132 months (mean 83.4 months) of the follow-up period.
      After the operation, 3 cases required steroid therapy during 4-50 months. We
      concluded that preoperative control of active inflammation, selection of
      operative procedures, timing for the operation, and the long-term precise
      management of the intractable disease were essential for successful treatment of
      aortitis syndrome with AAE.

PMID- 8530854
TI  - [The clinical value of MIBG myocardial spect before and after CABG--comparison
      with TI myocardial spect].
AB  - To evaluate the clinical usefulness of MIBG scintigraphy, 25 CABG patients
      underwent myocardial imaging using MIBG and TI. The result of this study
      indicated that the sensitivity of the MIBG was equivalent to that of the stress
      TI in detection of ischemic lesions. In spite of successful recanalization, only
      14 patients showed improvement of MIBG uptake, indicating that MIBG is not useful
      for detecting myocardial ischemia just after CABG. The decreased postoperative
      uptake of MIBG suggests that the CABG procedure may have caused denervation of
      the region.

PMID- 8530855
TI  - [Mediastinal schwannoma originating from the intrathoracic vagal nerve--a case
      report and review of the literature].
AB  - A 31-year-old woman was operated upon with the diagnosis of mediastinal tumor.
      The resected specimen revealed pathologically benign schwannoma originating from
      the right intrathoracic vagal nerve. The postoperative course was uneventful with
      no complication. Mediastinal schwannoma arising from the vagal nerve is rare. We
      discussed characteristics of this disease and reviewed the Japanese literature.

PMID- 8530856
TI  - [Hiatal hernia incarceration during cardiopulmonary bypass in patient with acute
      aortic dissection--a case report].
AB  - A 67-year-old woman was admitted to our hospital under diagnosis of Stanford type
      A acute aortic dissection. Chest CT showed aortic dissection from the ascending
      to descending aorta, and large hiatal hernia. Operation was undergone under
      cardiopulmonary bypass and circulatory arrest with retrograde cerebral perfusion.
      A graft replacement was carried out from the ascending to transverse arch aorta.
      After the release of the cross-clamping of aorta, the heart was gradually
      oppressed anteriorly by extrapericardial mass, so that the patient could not be
      weaned from the cardiopulmonary bypass. The mass was revealed incarcerated hiatal
      hernia by ultrasonography. After laparotomy, diaphragm and hiatus were incised,
      the incarceration was relieved and the diaphgragm was repaired with a Goretex
      sheet. Then the patient could be weaned from cardiopulmonary bypass. Her
      postoperative course was uneventful except for acute renal failure, and she was
      discharged 60 days after the operation. The incarceration of hiatal hernia was
      thought to be caused by tissue edema and small bleeding during cardiopulmonary
      bypass. This is the first reported case with the incarceration of hiatal hernia
      which occurred during cardiopulmonary bypass.

PMID- 8530858
TI  - [Direct implantation of the left coronary artery in BWG syndrome--sparing the
      shortage of distance with pulmonary arterial wall].
AB  - Anomalous origin of the left coronary artery (ALCA) arising from the pulmonary
      artery is a rare anomary, and causes myocardial infarction and death in children.
      Direct implantation of ALCA to the aorta was performed in the 6-year-old female
      patient. A large button of pulmonary arterial wall resected with ALCA could spare
      the shortage of the distance between the aorta and the ALCA. Postoperative
      catheterization displayed non-stenotic left coronary artery. Left ventricular
      function assessed by echocardiography showed improvement. Cold area in early
      stage postoperative myocardial imaging disappeared one year after the surgery,
      which suggested the hibernation of the preoperative myocardium.

PMID- 8530857
TI  - [Experiences of the approaches to heart for a patient with a tracheostoma].
AB  - The performance of open heart surgery in a patient with a tracheostoma can
      present difficult problems, including postoperative mediastinitis and inadequate
      operative exposure. Recently, we experienced two cases in which tracheostomy had
      been done preoperatively due to heart failure and reported the satisfactory
      results in this paper. Case 1; A 59-year-old woman who had mitral stenosis and
      massive regurgitation received mitral valve replacement and left atrial raphy.
      The approach to heart was performed in according to the following. A transverse
      submammary skin incision was made from right anterior axillar line to left
      mammary line and then a bilateral thoracotomy was made at the fourth intercostal
      space. Case 2; A 73-year-old man who had old myocardial infarction and
      postinfarction angina received coronary artery bypassgrafting to right coronary
      artery and left anterior descending branch, using saphenous vein grafts. A skin
      incision was placed at the second intercostal space in the fashion of "collar
      skin incision" and then made from the center of collar skin incision to the
      xiphoid process. The sternum was transected at the second intercostal space and
      divided longitudinally to the xiphoid process. These two approaches provided the
      adequate operative field. The cannulation of the ascending aorta, the superior
      vena cava and the inferior vena cava presented no difficulty and the operative
      procedure could be performed easily in a routine manner. We think that in a case
      of open heart surgery of a patient with a tracheostoma the approach in which the
      skin incision is distant from the area of a tracheostoma and no dissection near a
      tracheostoma is necessary have to be selected in order to decrease the risk of
      postoperative wound infection and mediastinitis.

PMID- 8530859
TI  - [Clinical experiences with the insertion of Dumon-type endotracheal stent tube
      for the patients with tracheal stenosis due to advanced esophageal carcinoma].
AB  - To relieve tracheal stenosis due to esophageal carcinoma, we have inserted Dumon
      type endotracheal stent tube to 2 patients with stenosis of the left main
      bronchus and a patient with tracheal stenosis. Severe dyspnea and stridor found
      in these patients was much improved in all three cases. After insertion of the
      stent tube to 2 patients with stenosis of the left main bronchus, radiation
      therapy with the dose of 65 Gy to main esophageal lesion was undergone, which
      resulted in the partial remission. These management allowed the patients to
      discharge. The last case with tracheal stenosis was due to recurrence of the
      esophageal carcinoma, which required additional insertion of the stent tube at
      the proximal site after initial insertion in a short period. We conclude that the
      quality of life and prognosis of patients with tracheal stenosis due to advanced
      esophageal carcinoma may be improved by the insertion of Dumon-type endotracheal
      stent tube.

PMID- 8530860
TI  - [Sex differentiation and Ad4BP].

PMID- 8530861
TI  - [Cytoskeletal SH3 proteins].

PMID- 8530862
TI  - [HN7-3/fork head (winged-helix) transcription factor family in dorso-ventral
      pattern formation of vertebrate embryos].

PMID- 8530863
TI  - [Metabolic zonation in rat hepatocytes].

PMID- 8530864
TI  - [Molecular mechanism of neurotransmitter release].

PMID- 8530865
TI  - [Induction of an additional limb by FGF and duplication of digits by Sonic
      hedgehog].

PMID- 8530866
TI  - [The structure and function of spherical viruses].

PMID- 8530867
TI  - [Enigma of rapamycin].

PMID- 8530868
TI  - [Regulation of neural differentiation by HES helix-loop-helix transcription
      factors].

PMID- 8530869
TI  - [Biological significance of nuclear matrix attachment regions (MAR) and tissue
      specific MAR-DNA binding proteins].

PMID- 8530870
TI  - [Regulation of phospholipase C-delta 1].

PMID- 8530871
TI  - [Calnexin is involved in the quality-control mechanism of the ER].

PMID- 8530872
TI  - [Molecular analysis of biological clocks].

PMID- 8530873
TI  - [Eukaryotic DNA replication: analysis of reconstitution of SV40 DNA replication].

PMID- 8530874
TI  - [Hemostasis and self-defense in insect].

PMID- 8530875
TI  - [14-3-3; a novel protein family which regulates intracellular signaling].

PMID- 8530876
TI  - The role of CD4+ tumor-infiltrating lymphocytes in human solid tumors.
AB  - Many, if not all, solid tumors are characterized by a T cell infiltrate, usually
      consisting of CD4+ and CD8+ T cells. Characterization of both subsets of tumor
      infiltrating lymphocytes (TIL) have shown that each population can be divided
      into tumor-specific and tumor-nonspecific T cells. A small proportion of tumor
      specific CD4+ TIL can directly lyse tumor cells in an HLA class I- or II
      restricted fashion. The majority of tumor-specific CD4+ TIL, however, recognize
      tumor antigens presented on HLA class II molecules by antigen-presenting cells
      (APC). At the same time, APC in the tumor environment express elevated levels of
      heat shock antigen (Hsp) 70 (and perhaps other antigens) that can be specifically
      recognized by tumor-nonspecific CD4+ TIL when presented by HLA class II.
      Functionally, CD4+ T cells can be distinguished into Th0 (production of IL-2, IL
      4, and IFN-gamma), Th1 (IL-2 and IFN-gamma), and Th2 (IL-4). In addition,
      stressed CD4+ TIL have the ability to produce the growth factors heparin binding
      epidermal growth factor and basic fibroblast growth factor that support tumor
      growth. Since the efficacy of an antitumor immune response is codetermined by the
      net effect of stimulatory and inhibitory cytokines, a detailed understanding of
      the developmental pathways of CD4+ TIL subsets and their interactions is critical
      for the design of clinical protocols.

PMID- 8530878
TI  - T helper cell dichotomy to Candida albicans: implications for pathology, therapy,
      and vaccine design.
AB  - Acquired immunity to Candida albicans is believed to prevent mucosal colonization
      of adult immunocompetent individuals from progressing to symptomatic infection.
      Resistance to disease appears to correlate with the detection of delayed-type
      hypersensitivity responses in vivo and a T helper type 1 (Th1) cytokine secretion
      profile in vitro. Cellular immunodeficiency, particularly HIV infection, greatly
      increases the risk of mucosal infection, confirming that CD(4+)-cell-directed
      immunity is effective locally in controlling infectivity of the yeast. While Th1
      type CD4+ cell activation resulting in phagocyte-dependent immunity clearly
      represents an important mechanism of anticandidal resistance, clinical
      observations suggest that Th2-type CD4+ cell reactivity may be triggered by
      Candida antigens in several disease states, including symptomatic infections and
      immunopathology. This may imply that a Th1-type pattern of reactivity
      characterizes the saprophytic yeast carriage and resistance to disease by healthy
      humans, whereas Th2-type responses would be mostly associated with pathology.
      Moreover, Candida-specific T helper responses, namely humoral and cell-mediated
      immunity, appear to be reciprocally regulated, as typically occurs in
      experimental models of parasitic and retroviral infection, where the Th1/Th2
      paradigm of acquired immunity has been best characterized. Recent studies,
      besides providing direct evidence for the occurrence of cross-regulatory Th1 and
      Th2 responses in mice with candidiasis, emphasize the potential of
      cytokine/anticytokine therapy for recruiting Candida-specific responses toward
      protective, Th1-type CD4+ cell reactivity. At the same time, these studies call
      attention to the possible consequences of C. albicans infection for
      immunopathology, allergy, and coinfection.

PMID- 8530877
TI  - Mechanisms of the pathogenic autoimmune response in lupus: prospects for specific
      immunotherapy.
AB  - A major step towards understanding the basic mechanism of systemic lupus
      erythematosus (SLE), the prototypic autoimmune disease that develops
      spontaneously, has been the identification of nucleosomes as a primary immunogen
      in this disease. The production of pathogenic autoantibodies in SLE results from
      an MHC class-II-restricted, cognate interaction between select populations of T
      helper cells and B cells that are specific for nucleosomal components. These
      observations pave the way for specific immunotherapy that blocks this pathogenic
      T and B cell interaction.

PMID- 8530879
TI  - Selective mechanisms utilized by persistent and oncogenic viruses to interfere
      with antigen processing and presentation.
AB  - Cell-mediated immunity is effective against cells harboring active virus
      replication, and is critical for the elimination of ongoing infections,
      regression of virus-associated tumors, and reducing or preventing the
      reactivation of persistent viruses. The capacity of persistent and oncogenic
      viruses to maintain a long-term relationship with their host presupposes viral
      mechanisms for circumventing antiviral defenses. By suppressing the expression of
      molecules associated with antigen processing and presentation, viruses abrogate
      the major immune mechanism that deals with the elimination of infected and tumor
      cells. This is accomplished either by transcriptional downregulation of genes
      encoding class I MHC antigens, peptide transporter molecules, and the proteasome
      associated LMP subunits, or by interfering with transport of class I molecules to
      the cell surface. In some cases viruses shut off the expression of most viral
      proteins during latency or express mainly nonimmunogenic or antagonistic peptide
      epitopes. This review describes selective mechanisms utilized by viruses for
      interference with antigen processing and presentation, and addresses their
      significance for in vivo viral persistence and tumor progression.

PMID- 8530881
TI  - [Cervical flexion myelopathy: clinical, morphological and biochemical studies on
      the soft tissues of the cervical spine in young-age operated cases].
AB  - To investigate the pathology of cervical flexion myelopathy among younger people,
      clinical, morphological and biochemical studies were performed in six cases (four
      males and two females) treated by posterior fusion. X-ray films showed, in all
      cases, scoliosis in the cervical spine as well as a reduction in the sagittal
      diameter and an anterior deviation in the spinal cord at the time of flexion.
      Spinal atrophy in the sagittal plane and crescent-shaped high contrast areas
      posterior to the dural tube were also observed on MRI images. Surgical findings,
      showed substantial expansion by the veins posterior to the dural tube in five
      cases with four showing accompanying organization. Morphological studies showed
      that in the musculus splenius capitis, the type 1 fibers were slightly more than
      in normal tissues. Moreover in one case, we observed neurogenic lesions such as
      the predominance and atrophy of type 2 fibers. Biochemical analyses of the
      collagen from muscles and skin showed immature collagen fibers, which was marked
      particularly in skin. The above results suggested that abnormalities in the
      collagen fibers in the soft tissues were related to the pathogenesis of cervical
      flexion myelopathy.

PMID- 8530882
TI  - [Idiopathic scoliosis by spinal fusion and brace treatment: evaluation by gait
      analysis].
AB  - We have investigated the differences in gait between 68 idiopathic scoliosis
      patients and 186 normal subjects, and differences in gait before and after
      treatment of the scoliosis by two different methods. The idiopathic scoliosis
      patients were divided into two groups according to which treatment they had
      received; one group of 17 cases had been treated by spinal fusion and the other
      group of 51 cases had been treated by bracing. Gait analysis was performed using
      a 1.2 m wide and 10.8 m long force plate walkway. Three components of each step
      (the lateral, horizontal and vertical components) were measured. Gait velocity,
      step length, step width and cadence were evaluated as temporal and distance
      factors, and symmetry, reappearance, smoothness, sway, rhythm and impact were
      evaluated as gait factors. RESULTS: Before treatment, there was no difference in
      any temporal or distance factor between the scoliosis patients and the normal
      subjects. However, the index of symmetry, and of sway, in the vertical component
      prior to treatment in the scoliosis patients was significantly inferior to that
      in the normal subjects. A positive correlation was found between the index of
      sway in the vertical component and the pretreatment Cobb angle. This correlation
      was found in the right-convex single curve group and in the double curve group,
      but not in the left-convex single curve group. After spinal fusion, the step
      width became wider and the index of sway significantly improved, but index of
      symmetry was unchanged. No gait factor became worse postoperatively. In contrast,
      in the bracing group, the step width became wider, but the index of symmetry, and
      of sway in the vertical component, did not improve with the brace. The gait of
      scoliosis patients could be objectively and quantitatively analyzed by the force
      plate. The gait analysis was useful for evaluating the effects of spinal fusion,
      and of brace treatment, in idiopathic scoliosis patients.

PMID- 8530883
TI  - [Electromyographic findings in muscles around the osteoarthritic knee: integrated
      electromyography and frequency analysis].
AB  - An evaluation of the muscular functions of the vastus medialis, vastus lateralis,
      rectus femoris, medial hamstring, and of the lateral hamstring was performed
      using electromyography in 33 knees of 26 female patients with osteoarthritis (OA
      group) and in 25 knees of 19 healthy female volunteers (control group). During
      standing on both feet, all muscles in the OA group showed higher IEMG (integrated
      electromyography) and higher LMR (IEMG of vastus lateralis/IEMG of vastus
      medialis ratio in the quadriceps; and lateral hamstring/medial hamstring ratio in
      the hamstrings) than the control group. These augmentary muscular activities
      ameliorated the varus deformity caused by the osteoarthritis. During maximum
      isometric voluntary contraction, the OA group showed lower extension and flexion
      torque of the knees and also lower IEMG than to the control group, while the IEMG
      of vastus lateralis was not lower. These findings indicated decreased muscular
      activities in the osteoarthritic knee, and that the activity of the quadriceps
      was maintained mainly by the vastus lateralis under such conditions. Frequency
      analysis of the myoelectric signal during maximum isometric voluntary contraction
      revealed a single peak of low frequency in the power spectrum density function of
      the quadriceps and double peaks of low and of high frequency in the hamstring. In
      the OA group, the peak height of the low frequency component was increased in the
      quadriceps and decreased in the hamstring. We concluded that the duration of the
      motor unit action potentials was affected in the osteoarthritic knee.

PMID- 8530880
TI  - Multisubunit receptors in the immune system and their association with the
      cytoskeleton: in search of functional significance.
AB  - Various multisubunit receptors of the immune system share similarities in
      structure and induce closely related signal transduction pathways upon ligand
      binding. Examples include the T cell antigen receptor (TCR), the B cell antigen
      receptor (BCR), and the high-affinity receptor for immunoglobulin E (Fc epsilon
      RI). Although these receptors are devoid of intrinsic kinase activity, they can
      associate with a similar array of intracellular kinases, phosphatases and other
      signaling molecules. Furthermore, these receptor complexes all form an
      association with the cytoskeletal matrix. In this review, we compare the
      structural and functional characteristics of the TCR, BCR and Fc epsilon RI. We
      examine the role of the cytoskeleton in regulating receptor-mediated signal
      transduction, as analyzed in other well-characterized receptors, including the
      epidermal growth factor receptor and integrin receptors. On the basis of this
      evidence, we review the current data depicting a cytoskeletal association for
      multisubunit immune system receptors and explore the potential bearing of this
      interaction on signaling function.

PMID- 8530884
TI  - [Experimental deformation in a bone fixation plate: measurement using holographic
      interferometry].
AB  - The minute mechanical properties of the tibia fixed by a metal plate and screws
      were investigated under various simulated loading conditions. The bracing
      technique and the design of the osteosynthetic plate are discussed based on the
      measurement results. The specimens were eight dried human tibias. Four different
      fixation method were employed using an AO plate system, and also using an Eggers
      plate system. The bending force, torsion force and axial force were applied to
      the tibia. Deformation in the tibia and/or metal plate was measured using double
      exposure holographic interferometry. The mechanical properties were estimated
      from the fringe pattern and from the deformation curve obtained from the
      reconstruction image of the holographic interferometry. The fixation capability
      of the plate systems differed according to the direction of the loading. The
      reconstruction image of the hologram showed that deformation increased mainly in
      the plate corresponding to the fracture line of the tibia. Screws nearer the
      fracture line were more important in increasing the fixation capability of the
      plate. Twisted deformations in the plate were observed under a simple bending
      force. The new measurement method of holographic interferometry clearly showed
      the two dimensional bending and the twisted deformation in detail.

PMID- 8530885
TI  - [Bone histomorphometric osteopenia induced by ovariectomy or diabetes mellitus in
      rat].
AB  - To discover the risk factors associated with the occurrence of osteoporosis, the
      development of osteopenia and bone remodeling through bone histomorphometry on
      the proximal tibia was observed in female Wistar rats subjected to either
      ovariectomy (OVX) and/or diabetes mellitus. Diabetic rats were obtained by the
      intra-abdominal administration of 30 mg/kg streptozotocin (STZ). Single-loaded
      groups were the OVX group and the STZ group, while the combined group was the
      OVX+STZ group. Each group was further divided into two subgroups according to the
      experimental periods of 3 months and of 6 months. Bone histomorphometry was
      performed on the tibial metaphysis. The results showed a significant bone volume
      decrease in both the single-loaded groups at 3 months. The decrease was greater
      in the STZ group than in the OVX group. In the single-loaded groups at 6 months,
      there were even greater decrease. The combined group showed a smaller bone volume
      decrease after 3 months than the STZ group and the OVX group. However, at 6
      months, the combined group showed a bone volume decrease significantly greater
      than the single-loaded OVX group. The bone-formation related parameters (osteoid
      surface, osteoid volume, mineralizing surface, mineral apposition rate, and bone
      formation rate parameters) of the STZ group and the OVX+STZ combined group at 3
      months showed a considerable decrease in bone volume; no double labeling surfaces
      were observed in the 6-month OVX+STZ group; there was also a decrease in the
      osteocalcin level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8530886
TI  - [Histological changes, muscle force and fatigability after electrical stimulation
      to experimentally paralyzed muscles].
AB  - In order to use functional electrical stimulation effectively in paralyzed muscle
      treatment, changes in the maximal muscle force, muscle fatigue, and histological
      changes were evaluated in electrically stimulated muscles. Study 1. Tissue damage
      by percutaneous intramuscular electrodes implanted into the quadriceps muscle was
      examined in rat. Stimulation was conducted at various output voltages, and for
      various durations of time, in order to assess the histological changes in the
      muscle around the electrodes. Study 2. Electrodes were implanted into the
      bilateral quadriceps and gastrocnemius muscles of adult cat, and the unilateral
      muscles were then stimulated from 3 weeks following the transection of the spinal
      cord at the T9 level. Stimulus parameters were divided into two groups; as "A"
      stimulation: at -8V for 15min twice/week, and as "B" stimulation: at -16V for 30
      min 4 times/week. The histological changes were examined using the myofibrillar
      ATPase method to determine the diameters and occupation ratios for each muscle
      fiber type. RESULTS. Study 1. Significant tissue damage began to occur when the
      voltage output created the maximum muscle contraction force. Until that critical
      voltage point was reached, tissue damage was not significant, regardless of the
      duration of the stimulation. Study 2. The maximum muscle force decreased until 4
      weeks after the transection, then increased regardless of the presence of
      electrical stimulation. The muscle fatigability of the non-stimulated muscle was
      greater than that of the stimulated muscle. High voltage, long duration, and
      frequent stimulation was effective in controlling fatigue. The ratio of type I
      fibers was higher in the stimulated muscle. There was no evidence, however, of
      suppressing muscle fiber atrophy after electrical stimulation. These results
      suggested that electrically stimulating paralyzed muscles was effective for
      suppressing muscle fatigue, and for reducing the ratio of type I fibers. In
      clinical use, the output voltage should be kept below the voltage that induces
      the maximum muscle contraction to prevent tissue damage.

PMID- 8530887
TI  - [Gamma ray-irradiation in fresh allo-joint transplantation].
AB  - In the first of a series of experiments in rat designed to assess the efficacy of
      gamma ray irradiation in fresh allo-joint transplantation, it was found that the
      optimal gamma ray dosage was 4 Gy. At this dosage level, the irradiation rays
      suppressed the viability of marrow cells which had the highest antigenicity, with
      no injury to the bone or articular cartilage. In a second experiment, a fresh
      homologous knee joint was irradiated at 4 Gy and then transplanted while
      administering the donor's splenic cell suspension (for specific
      immunosuppression) and the immunosuppressive agent cyclosporine (5 mg/kg) to the
      recipient rat. All the rats that received a pre-irradiated knee joint graft
      survived until sacrificed for evaluation without showing any sign of host
      rejection. In these rats, bone fusion had occurred between the host bone and the
      graft by the 8th postoperative week. Degeneration of the articular cartilage was
      similar between the rats that had received a pre-irradiated graft and those that
      had not. These findings indicated that 4 Gy gamma ray irradiation to a graft
      before transplantation provided an effective means of immunosuppression.

PMID- 8530888
TI  - [Effects of prostaglandin E2 and sodium hyaluronate on bradykinin induced knee
      joint pain in rat].
AB  - We studied effects of prostaglandin E2 and sodium hyaluronate on the reactive
      muscle activity induced by intra-articular injection of bradykinin into the knee
      joint of rat. An animal model was developed to evaluate knee joint pain. In
      unanesthetized and spinalized rat, bradykinin (BK) was injected into the knee
      joint and the duration of the reactive activity of the knee flexor was evaluated.
      The duration of the reaction was elongated dependent on the injected BK dosage
      (0.025-2.5 micrograms). When prostaglandin E2 (PG E2) was injected with BK, the
      duration of the reaction increased significantly (p < 0.01). In contrast, sodium
      hyaluronate (Na-HA: average MW 900 kD) injected into the joint 3-24 hours in
      advance significantly inhibited the BK induced reaction (p < 0.05-0.01). A
      histological study demonstrated the fluorescein-labeled Na-HA diffusely
      infiltrating into the surface of the soft tissue. From these results, the animal
      model used in the present study was valuable to evaluate quantitatively knee
      joint pain. Furthermore, the sensitizing effect of PG E2 and the inhibitory
      effect of Na-HA on joint pain was objectively demonstrated.

PMID- 8530889
TI  - [Retinoic acid-induced hyperostosis in the murine spine, particularly in the
      cervical spine].
AB  - In order to investigate the role of retinoic acid in inducing spinal
      hyperostosis, the murine spine was radiologically and histologically examined
      after a 24-week peroral administration of synthetic retinoic acid (etretinate).
      In the cervical spine, osteophytes on the ventral rims of the vertebral bodies
      were more developed after etretinate administration than in controls.
      Histologically, chondrocytes after etretinate administration proliferated in the
      anterior longitudinal ligaments at the junction of the ventro-caudal rim and the
      epiphyseal region of the C2 and C3 vertebral bodies. Endochondral ossification
      was a characteristic feature and immature chondrocytes and mesenchymal cells were
      found in the region. After etretinate administration, the incidence of
      proliferative changes was 67.6% at the C2 ventro-caudal rim, and 79.4% and 70.6%,
      respectively in the C2 and C3 ventral epiphyseal regions. These percentages were
      highly significant compared with controls, but they were not dosage-dependent.
      These findings suggested that retinoic acid was involved in the differentiation
      and proliferation of chondrocytes in ligaments.

PMID- 8530890
TI  - [An experimental study on recovery of lacerated skeletal muscle: correlation
      between separation gap and the potential for recovery].
AB  - Skeletal muscle has a potential for recovery with muscle tissue when the
      lacerated stumps are maintained in contact. However, when there is no contact,
      this potential for recovery is unknown. Here we report our studies on the
      correlation between the recovery and the separation distance between the stumps
      in partially lacerated muscles in Wistar rat. The gastrocnemius muscle was
      subjected to a partial wedge-shaped laceration which allowed the surrounding
      tissue to hold a constant separation distance between the stumps throughout the
      duration of the study. Groups each of 7 rats were examined at 1, 2, and at 4
      days, and at 1, 2, 2, and at 6 weeks after the laceration was performed. In each
      group, 5 rats underwent histological and immunohistological examinations, while
      the other 2 underwent electronmicroscopic examination. The muscle stumps
      initially degenerated, and then began to regenerate at 4 days after the
      laceration. During this period, local basement membranes remained intact allowing
      regeneration of muscle fibers. However, the absence of basement membrane between
      the stumps led to a random regeneration pattern of myotubes growing into the
      granulation tissue in the wedge-shaped gap. The electronmicroscopic findings
      showed that these growing myotubes had no basement membrane. The maximum growth
      of these myotubes was found to be 1.20 +/- 0.31 mm reached at 3 weeks after the
      laceration, suggesting that the maximum gap was approximately 1.0 mm across which
      there is a potential for recovery through regeneration.

PMID- 8530891
TI  - [Chondrogenic potential of a free autogenous periosteal graft for biological
      resurfacing over a half-thickness defect in a joint surface: an experimental
      study].
AB  - We report the results of chondrogenesis from a free autograft of periosteum taken
      from the medial tibial condyle transplanted over a partial-thickness defect
      created on the medial femoral articular surface in immature white rabbit. A total
      of 69 rabbits were randomly divided into four groups as follows, Group I received
      the free autograft and were allowed intermittent activity in a cage. Group II
      also received a free autograft but were allowed only continuous passive motion in
      a CPM apparatus for 8 hours a day for the first two weeks after the operation.
      Group III received a freeze-dried periosteal graft and were allowed intermittent
      activity in a cage. And Group IV as controls received no graft over the created
      defect and were allowed intermittent activity in a cage. In specimens from Group
      I and from Group II at 3 weeks postoperatively, hypertrophic cells were
      recognized. In both groups at 4 weeks postoperatively, the autograft had sealed
      the defect with interposition of fiber bundles. At 8 weeks postoperatively, the
      union of both matrices was clearly demonstrated. The chondrocyte arrangement and
      matrix bonding was observed to be better in Group II than in Group I. In
      specimens from Group III at 8 weeks postoperatively, the freeze-dried periosteum
      had deteriorated without sealing the defect. In Group IV at 8 weeks
      postoperatively, the surface of the shaved cartilage was irregular and similar to
      that in arthrosis. These findings indicated that a periosteal free autograft
      produced bonding between the matrix of the graft and the matrix of the host
      cartilage, and was therefore effective for chondrogenesis to seal over a joint
      defect.

PMID- 8530892
TI  - [Changes in the visco-elastic properties of the articular cartilage incubated in
      various kinds of liquid].
AB  - The purpose of our experiment was to investigate the way in which the visco
      elastic properties of the articular cartilage of a loading joint responded to
      various liquid environments. Using articular cartilage extracted from the femoral
      head of a cow, we examined the viscoelasticity of the articular cartilage under a
      fixed load while it was immersed in distilled water, isotonic salt water,
      hypertonic salt water, and in hyaluronic acid. A stainless steel rod with a
      diameter of 1.5 mm was applied directly to the articular cartilage (weighing 25,
      50 and 100 grams) and the resultant visco-elastic curves were measured. Results
      showed that the deformation change to the cartilage was greatest while it was
      immersed in hypertonic salt solution and smallest while immersed in distilled
      water. Secondly, when immersed in hyaluronic acid solution, the change in
      deformation proved to be greater when the solution was denser and the molecular
      weight heavier and the hyaluronic acid could not penetrate into the cartilage
      matrix and remained at the surface. These results demonstrated that the visco
      elastic property of the articular cartilage was affected not only by the varying
      osmotic pressures on the internal parts of the cartilage, but also on the density
      of the solution surrounding the cartilage and on the different water
      retainability of that cartilage.

PMID- 8530893
TI  - [Pain mechanisms in reflex sympathetic dystrophy].

PMID- 8530894
TI  - A Mexican perspective on learning disabilities.
AB  - Given the worldwide trend toward the integration of children with special needs
      into the general school system, and the Program for Educational Modernization
      (1989-1994) in Mexico, Mexican educators have had to reassess the politics of
      special education, focusing on different service delivery models. One model,
      Integrated Groups, which has been functioning since the 1970s and is primarily
      for children with learning and language disabilities, is described. New
      legislation recently enacted recognizes and encourages the collaboration of
      general education and special education to meet the needs of all children. During
      the school year 1994-1995, the Secretariat of Public Education (SEP; the Mexican
      centralized public school system) is piloting, in Mexico City, a proposal for the
      integration of children into the general classroom. This new model of service
      delivery is designed to provide greater site-based approaches to the education of
      individuals with learning disabilities.

PMID- 8530895
TI  - Linking the needs of students with learning disabilities to a whole language
      curriculum.
AB  - As a curricular approach to language arts instruction, whole language has gained
      prominence in the last decade. Many researchers and practitioners working in the
      field of learning disabilities have questioned the appropriateness of whole
      language for students considered to be learning disabled. In this article a
      rationale is presented for how the whole language approach provides the type of
      environment that is particularly suitable for these students. This is developed
      by analyzing the documented characteristics of these learners and the
      implications of those characteristics within a whole language curriculum.

PMID- 8530896
TI  - Educating children with learning disabilities in Foxfire classrooms.
AB  - Because every classroom in American schools contains heterogeneous groups of
      students, inclusion is more than an issue of concern just for special educators.
      This article provides examples of elementary classrooms that have adopted the
      Foxfire approach to instruction as a means of developing learning communities
      that serve all children. The teachers who are described turned to learner
      centered instruction not as a method to promote the inclusion of children with
      learning disabilities, but, rather, as a means of providing optimal learning
      experiences for all their students. The rationale for developing elementary
      classrooms that are learner-centered communities is explored, and specific
      examples of instructional approaches are provided.

PMID- 8530897
TI  - Exploring writing--from rebellion to participation.
AB  - This article describes the unfolding of one student's encounter with writing. It
      was not an encounter of miraculous proportions, but, rather, one that became
      apparent through a teacher's careful observations of the engagement of a
      nonwriting third grader with print. This encounter may have been one of the first
      times the student realized he could be literate.

PMID- 8530898
TI  - The assurance of things hoped for: coping behavior of children with language
      disorders in a process-writing environment.
AB  - This article describes the experience of first- and second-grade students as they
      put together the pieces of literacy knowledge necessary for each to discover a
      writing process that produces readable work. Woven into the description is the
      unfolding of the author's own understanding of how to help her students make
      sense of the literacy code.

PMID- 8530899
TI  - In knowing our students ourselves.
AB  - This article describes the relationship between a middle school student teacher
      and one of her students with learning handicaps. Through a series of interviews
      and observations for 1 school year, the teacher learned about the needs of this
      student and also developed insights into teaching, particularly related to
      students with learning disabilities. Jimmy was a sixth grader with a first-grade
      reading level. He revealed his tricks and methods for getting out of reading to
      the teacher, who was amazed that he made it so far without reading. The teacher's
      feelings changed from hopeless at first to hopeful and proud by the end of the
      year. During the interviews, Jimmy described how he would get very nervous when
      he was asked to read, and quickly start trouble to disrupt the class and be sent
      to the principal's office. He would often fake sickness and be sent to the nurse,
      just to get out of reading. This interview process not only enlightened the
      teacher about her student, but also created a vehicle for her to form a working
      relationship with her student. This relationship was essential to Jimmy's
      beginning to read.

PMID- 8530900
TI  - Macbeth in the resource room: students with learning disabilities study
      Shakespeare.
AB  - A teacher describes a secondary English unit on Shakespeare implemented in a
      manner designed to take advantage of the learning differences of resource room
      students. After developing and investigating questions relating to Macbeth,
      students then read and enjoyed the drama. As a result of acquiring an
      understanding of Shakespeare exceeding that of students in general classes, self
      esteem and academic motivation increased. Finally, connections to practice and
      behavioral, constructivist, feminist, and critical theories are discussed.
      Appendices describe specific schedules and routines.

PMID- 8530901
TI  - Valuing differences: the children we don't understand.
AB  - The author of this essay shares her personal experiences as a teacher of young
      children, and her professional approach to facilitating growth in unique
      children. The author suggests that as educators, our responsibility lies not in
      explaining differences in young children or labeling and diagnosing differences,
      but in responding to those unique differences in the classroom by supporting
      students and utilizing their strengths. The author suggests that responsive
      teaching requires educators to listen to children and reflect upon their
      practice.

PMID- 8530902
TI  - Operationalizing a definition of learning disabilities.
AB  - Past, present, and future concerns regarding the definition of learning
      disabilities (LD) are documented. Research on efforts to clarify the LD label is
      discussed, with a focus on the questionable utility of the discrepancy model.
      Finally, an approach to operationalizing the NJCLD definition of LD is presented
      and applied.

PMID- 8530903
TI  - The management of the perforated uterus in conjunction with 1st trimester
      abortions.

PMID- 8530904
TI  - The life and times of Dean Jim Pittman, M.D.

PMID- 8530905
TI  - A case of Kawasaki's disease appearing as staphylococcal scalded-skin syndrome.

PMID- 8530906
TI  - Talking with parents following sudden infant death syndrome.

PMID- 8530907
TI  - Actinomycosis in Alabama.

PMID- 8530908
TI  - The changing status of diphtheria immunity: serological survey of Alabamians in
      two counties.

PMID- 8530909
TI  - A new epidemic is killing our children ... and everyone can help immunize them!

PMID- 8530910
TI  - Process dissociation, single-process theories, and recognition memory.
AB  - According to the assumptions of L. L. Jacoby's (1991) process dissociation
      method, performance in recognition memory is determined by the combination of an
      unconscious familiarity process and a conscious intentional recollection process.
      The process dissociation method is used to produce estimates of the contributions
      of the 2 components to recognition performance. This article investigates whether
      the method provides the correct estimates of components if performance actually
      depends on only a single process or on 2 processes different from those assumed
      by the method. The SAM model (G. Gillund & R. M. Shiffrin, 1984) was used to
      produce simulated data based on a single process. Variants of SAM with 2
      processes and R. C. Atkinson and J. F. Juola's (1973) 2-process model were used
      to produce data based on 2 processes.

PMID- 8530911
TI  - The uncertain response in the bottlenosed dolphin (Tursiops truncatus).
AB  - Humans respond adaptively to uncertainty by escaping or seeking additional
      information. To foster a comparative study of uncertainty processes, we asked
      whether humans and a bottlenosed dolphin (Tursiops truncatus) would use similarly
      a psychophysical uncertain response. Human observers and the dolphin were given 2
      primary discrimination responses and a way to escape chosen trials into easier
      ones. Humans escaped sparingly from the most difficult trials near threshold that
      left them demonstrably uncertain of the stimulus. The dolphin performed nearly
      identically. The behavior of both species is considered from the perspectives of
      signal detection theory and optimality theory, and its appropriate interpretation
      is discussed. Human and dolphin uncertain responses seem to be interesting
      cognitive analogs and may depend on cognitive or controlled decisional
      mechanisms. The capacity to monitor ongoing cognition, and use uncertainty
      appropriately, would be a valuable adaptation for animal minds. This recommends
      uncertainty processes as an important but neglected area for future comparative
      research.

PMID- 8530912
TI  - Mechanism of tongue protraction during prey capture in the spadefoot toad Spea
      multiplicata (Anura: Pelobatidae).
AB  - Recent studies have used muscle denervation experiments to examine the function
      of muscles during feeding in frogs. By comparing the results of denervation
      experiments among taxa, it is possible to identify evolutionary changes in muscle
      function. The purpose of this study was to examine the function of jaw and tongue
      muscles during prey capture in Spea multiplicata, a representative of the
      superorder Mesobatrachia. All members of this group possess a disjunct hyoid
      apparatus. We predicted that Spea would possess a novel mechanism of tongue
      protraction on the basis of its hyoid morphology. High-speed video motion
      analysis and muscle denervation were used to study the feeding behavior and
      mechanism of tongue protraction in Spea. Although Spea possesses a relatively
      long tongue, its feeding behavior is similar to that of short-tongued frogs of
      similar body size. Denervation of the m. submentalis had no effect on feeding
      behavior. When the m. geniohyoideus was denervated, the tongue pad was raised and
      moved forward slightly, but did not leave the mouth. When the m. genioglossus was
      denervated, the tongue pad was raised slightly, but no forward movement of the
      tongue occurred. A similar result was obtained after the mm. genioglossus and
      geniohyoideus were denervated simultaneously. Thus, both the mm. genioglossus and
      geniohyoideus are necessary for normal tongue protraction in Spea. In contrast,
      only the m. genioglossus is necessary for normal tongue protraction in
      archaeobatrachians and neobatrachians. We hypothesize that the disjunct hyoid is
      responsible for the greater role of hyoid movement during feeding in
      mesobatrachians.

PMID- 8530913
TI  - Assembly of somatic histone H1 onto chromatin during bovine early embryogenesis.
AB  - We have examined the distribution of somatic histone H1 in bovine oocytes and
      preimplantation embryos, using an antibody that recognizes histone H1 subtypes
      present in somatic cells. Immunoreactive H1 was not detectable on the chromosomes
      of metaphase II of meiosis nor in the nuclei of early cleavage-stage embryos. In
      most embryos, immunoreactive H1 was assembled onto embryonic chromatin during the
      fourth to sixth cell cycle after fertilization. No immunoreactive somatic histone
      H1 was detected, however, when embryos were incubated in the presence of alpha
      amanitin beginning early during the fourth cell cycle. These results indicate
      that somatic subtypes of histone H1 are assembled onto embryonic chromatin in a
      developmentally regulated manner that requires embryonic transcription.
      Aphidicolin, an inhibitor of DNA replication, also inhibited the assembly of
      somatic histone H1 onto chromatin when present at early stages of the 4th cell
      cycle. It is suggested that, because the bulk of histone gene expression in
      proliferating cells occurs during DNA replication, expression of genes encoding
      immunoreactive H1 is inhibited in embryos blocked before or soon after entering
      the S-phase. These findings on the control of somatic histone H1 assembly onto
      chromatin in cattle show a remarkable similarity to those found in the mouse.
      Such evolutionary conservation suggests that the somatic histone H1 complement of
      chromatin may regulate critical aspects of chromatin activity during mammalian
      oogenesis or early embryogenesis.

PMID- 8530914
TI  - Acquisition of nerve dependence for the formation of a regeneration blastema in
      amputated hindlimbs of larval Xenopus laevis: the role of limb innervation and
      that of limb differentiation.
AB  - In larval and adult urodeles and late-stage larval anurans, blastema formation
      after limb amputation requires an adequate nerve supply. Experimental evidence
      obtained from aneurogenic limbs indicates that, in urodeles, the acquisition of
      nerve dependence during embryonic development is due to the "addiction" of limb
      tissues to factors released by the ingrowing nerves rather than to limb
      differentiation. The aim of this work was to establish whether, in the toad
      Xenopus laevis, nerve-dependence for blastema formation after hindlimb
      amputation, which is acquired gradually during larval development and becomes
      complete at stage 57 is due to limb innervation or to limb differentiation. Two
      series of experiments were carried out. In the first series, limb differentiation
      was inhibited by treating the larvae with an anti-thyroid drug, and innervation
      was maintained for an interval much longer than that normally required for
      development from nerve-independent stages to stage 57. In the second series, the
      limb was caused to differentiate in the absence of nerves by maintaining the
      limbs denervated. Limb differentiation was often accelerated by treating early
      stage larvae with thyroxine or by grafting early-stage limbs onto denervated
      limbs of late larvae, which, being near metamorphic climax, possessed high levels
      of circulating thyroid hormones. Results showed that in the first series of
      experiments the denervated limbs formed regeneration blastemas after amputation,
      but in the second series they did not. It was therefore concluded that the
      acquisition of nerve dependence for blastema formation in larval Xenopus laevis
      is not directly imposed by factors released by the nerve fibers, but is strongly
      related to differentiation of limb tissues.

PMID- 8530915
TI  - Extrusion of microtubule doublet outer dense fibers 5-6 associating with fibrous
      sheath sliding in mouse sperm flagella.
AB  - Our previous experiments (Si and Okuno [1993a] Exp. Cell Res., 208:170-174)
      provided evidence that the fibrous sheath (FS) slid headward to middle piece in
      the activated mouse sperm flagellum when doublet microtubules together with their
      outer dense fibers (ODFs) extruded from the axoneme. Of the extruded doublet
      ODFs, however, which one was responsible for the FS sliding remained unresolved.
      The present study demonstrated that the FS sliding and the order of doublet-ODFs
      extrusion in mouse sperm flagella were trypsin concentration dependent. Under the
      condition of mild trypsinization (0.1 micrograms/ml), only doublet-ODFs 4, 5-6
      (doublet-ODFs 5 and 6 were always paired), and 7 extruded from the axoneme.
      Furthermore, the extrusion of doublet-ODFs 5-6 was identified to precede doublet
      ODFs 4 and 7, and was considered the candidate responsible for FS sliding. In
      contrast, the high-concentration trypsinization (4 micrograms/ml) led to
      extrusion of doublet-ODFs 1, 2, and 9 following doublet-ODFs 4, 5-6, and 7. FS
      sliding, however, did not occur.

PMID- 8530916
TI  - The effects of category distinctiveness and stimulus relations on young
      children's use of retrieval clustering strategies.
AB  - The influence of category distinctiveness and the associative relatedness of
      within-category items on young children's use of an organizational clustering
      strategy at retrieval was examined. Children from preschool and Grades 1 and 3
      studied and recalled 9-item sets of pictured items representing either
      distinctive categories (e.g., numbers, letters, animals) or standard categories
      (e.g., furniture, clothing, animals). Half of the children at each grade level
      and in each category-type condition received category exemplars that were high
      associates. The results showed that each of the grade levels exhibited above
      chance clustering for the distinctive categories but not for the standard
      categories. However, preschool participants attained above-chance clustering only
      for high-associate items, suggesting that their retrieval may have been driven
      automatically by natural word associations inherent in the stimuli. For older
      participants, above-chance clustering obtained for the low-associate as well as
      for the high-associate items, suggesting that they may have engaged in strategic
      retrieval activity.

PMID- 8530917
TI  - Effects of axial ligand replacement on the redox potential of cytochrome c.
AB  - The formal potentials (E0') and electron transfer numbers (n) of imidazole (Im),
      1-methylimidazole (1-MeIm), and 1-ethylimidazole (1-EtIm) complexes of cytochrome
      c have been determined for the first time using optically transparent thin-layer
      spectroelectrochemistry. In comparing these results with the E0' value of the
      cytochrome c, their potentials at infinite dilution have been calculated, which
      indicate that axial replacement of methionine-80 by Im, 1-MeIm, and 1-EtIm gives
      rise to 426, 359, and 327 mV negative shifts relative to that of native
      cytochrome c, respectively. Thereby, the origins of the effects of axial
      substitution on redox potential are discussed.

PMID- 8530918
TI  - Down-regulation of NADPH-diaphorase (nitric oxide synthase) may account for the
      pharmacological activities of Cu(II)2 (3,5-diisopropylsalicylate)4.
AB  - Purposes of this work were to develop an enzyme system as an in vitro model of
      the NADPH-dependent component of nitric oxide synthase (NOS) and examine the
      plausible down-regulation of this system and brain NOS by copper (II)2(3,5
      diisopropylsalicylate)4[Cu(II)2(3,5-DIPS)4] as a mechanism accounting for its
      analgesic, anticonvulsant, and other pharmacological activities. Porcine heart
      diaphorase (PHD) was found to oxidize 114 microM NADPH with the corresponding
      reduction of an equivalent amount of 2,6-dichlorophenolindophenol (DCPIP).
      Addition of Cu(II)2(3,5-DIPS)4 to the reaction mixture decreased the reduction of
      DCPIP without substantially affecting the oxidation of NADPH. The IC50 for
      Cu(II)2(3,5-DIPS)4 in inhibiting the reduction of DCPIP was 1.5 microM.
      Mechanistically, this inhibition of DCPIP reduction was found to be due to the
      ability of Cu(II)2(3,5-DIPS)4 to serve as a catalytic electron acceptor for
      reduced PHD, which was enhanced by the presence of a large concentration of DCPIP
      and inhibited by a large concentration of NADPH. Oxidation of NADPH by PHD in the
      absence of DCPIP was linearly related to the concentration of Cu(II)2(3,5-DIPS)4
      through the concentration range of 5-25 microM Cu(II)2(3,5-DIPS)4 with 50%
      recovery of NADPH oxidation by PHD at a concentration of 16 microM Cu(II)2(3,5
      DIPS)4. Whole rat brain tissue sections incubated in medium containing an NADPH
      generating system and nitroblue tetrazolium chloride (NBT) were less intensely
      stained when Cu(II)2(3,5-DIPS)4 was added to the medium. It is concluded that
      Cu(II)2(3,5-DIPS)4 serves as an electron acceptor in down-regulating PHD
      reduction of DCPIP and in down-regulating NOS in brain tissue sections. A
      decrease in NO synthesis in animal models of seizure, pain, and other disease
      states with Cu(II)2(3,5-DIPS)4 may account for the anticonvulsant, analgesic, and
      other pharmacological activities of this complex.

PMID- 8530919
TI  - The ultrafiltration and ESR study of Cd2+ binding to human erythrocyte spectrin.
AB  - The Cd2+ binding to human erythrocyte spectrin tetramer (SPT) was studied by the
      ultrafiltration method. The results indicate that the Cd2+ binding depends on
      Cd2+ concentration in a biphasic feature. Thus, it is different from the Tb(3+)
      SPT reaction. The biphasic feature is in accordance with the results of
      fluorescence and circular dichroism (CD) studies on Cd(2+)-SPT complex. The data
      were analyzed by the Scatchard method. At the first stage (the mole ratio of
      Cd2+/SPD < 45), there are two types of Cd2+ binding sites, with the binding sites
      and corresponding binding constants determined as: n1 = 6, K1 = 3.3 x 10(5) M-1;
      n2 = 8, K2 = 9.1 x 10(4) M-1. At the second state (Cd2+/SPD > 45), the Cd2+
      binding manifests a positive cooperative effect. The interaction between Cd2+ and
      maleimide spin labeled (MSL) SPT was studied by the ESR method. The results were
      fitted with the multiple equilibrium model, and one Cd2+ high-affinitive binding
      site with association constant 9.61(7) x 10(5) M-1 was obtained. The conjugation
      of maleimide with thiol group results in the decrease of Cd2+ high-affinitive
      binding sites from 6 to 1. This demonstrated that the thiol groups of SPT were
      involved in the high binding sites. The increase of mobile fraction of MSL in low
      Cd2+ concentration revealed that Cd2+ binding to SPT induces a significant
      conformation change of MSL-SPT. The rotation correlation time of MSL attached to
      SPT varied from 4.4 x 10(-9) to 6.5 x 10(-9) sec.

PMID- 8530920
TI  - Synthesis, structure, and biological activity of organotin compounds with di-2
      pyridylketone and phenyl(2-pyridyl) ketone 2-aminobenzoylhydrazones.
AB  - The ligand behavior of di-2-pyridylketone 2-aminobenzoylhydrazone (Hdpa), and
      phenyl(2-pyridyl)ketone 2-aminobenzoylhydrazone (Hdba) towards organotin
      derivatives was investigated. The synthesis and the IR and 119Sn NMR
      spectroscopic characterization of the compounds is reported, together with the X
      ray crystal structures of Hdpa and Sn(C6H5)3Cl(OH2).Hdpa, which are discussed and
      compared. The in vitro evaluation of antimicrobial properties revealed the strong
      activity of Sn(C6H5)2(Hdpa)Cl2 and Sn(C6H5)3Cl(OH2).Hdpa complexes. None of the
      compounds showed genotoxicity in the Bacillus subtilis rec-assay and in the
      Salmonella-microsome test.

PMID- 8530921
TI  - Platinum(II) complexes of 4-methoxy- and 4-chlorobenzoic acid hydrazides.
      Synthesis, characterization, and cytotoxic effect.
AB  - The complexes [Pt(NH3)(pmbah)Cl2], [Pt(NH3)(pcbah)Cl2], [Pt(pmbah)2X2] and
      [Pt(pcbah)2X2] (pmbah = 4-methoxybenzoic acid hydrazide, pcbah = 4-chlorobenzoic
      acid hydrazide; X = Cl, Br, I) have been synthesized and characterized by
      elemental analysis, electric conductivity, 1H NMR, IR, and electronic spectra. A
      cis-square planar structure with hydrazide ligands coordinated via the NH2 groups
      has been proposed for these compounds. The complexes, but not the free ligands,
      have shown a strong growth inhibitory effect in Friend leukemia cells in vitro,
      most of which are more active than cisplatin.

PMID- 8530922
TI  - Monomeric ferric heme peptide derivatives: model systems for hemoproteins.
AB  - Electron paramagnetic resonance spectra of a number of ferric heme peptide
      derivatives, in aqueous-detergent and various aqueous-alcohol solvent mixtures,
      have been obtained using samples in the concentration range 0.1-1.0 mM. Some of
      these were clearly monomeric, homogeneous, mixed-ligand adducts, entirely
      suitable for use as model systems for hemoprotein spectroscopic studies. As
      anticipated, the measured EPR parameters were largely independent of solvent
      environment. Surprisingly, micellar preparations of ferric heme undecapeptide in
      mildly alkaline solution showed no evidence for the formation of a hydroxide
      adduct, contrary to a previous report [S. Mazumdar, O. K. Medhi and S. Mitra,
      Inorg. Chem. 30 700 (1991)].

PMID- 8530923
TI  - Chelating agent inhibition of Trypanosoma cruzi epimastigotes in vitro.
AB  - A number of chelating agents and some of their derivatives are as effective as,
      or superior to, benznidazole, the compound currently in clinical use, in the
      suppression of the reproduction of epimastigotes of Trypanosoma cruzi, the
      protozoa that causes Chagas' disease. All compounds were examined at a culture
      concentration of 5 micrograms/mL. The most effective compounds included N,N,N',N'
      tetrakis(2-pyridylmethyl)ethylenediamine, sodium diethylamine-N-carbodithioate,
      piperidine-N-carbodithioate and several of its analogs, a number of other
      carbodithioates with two nonpolar groups on the nitrogen, and tetraethylthiuram
      disulfide, a prodrug of sodium diethylamine-N-carbodithioate and widely used in
      the treatment of alcoholism. The introduction of additional ionic or nonionic
      polar groups on the chelating molecule generally results in a loss of
      tyrpanocidal activity. Common commercially available chelating agents which
      exhibited no activity included D-penicillamine, meso-2,3-dimercaptosuccinic acid,
      and triethylenetetramine tetrahydrochloride. Dose-response data on the culture
      indicated that some of these compounds exhibited inhibition of Trypanosoma cruzi
      epimastigotes at concentrations as low as 0.625 microgram/mL. It is proposed that
      the mechanism of action of these compounds is based on their ability to interfere
      with the essential metal metabolism at intracellular sites of the epimastigote
      involving iron, copper, or zinc. The results also indicate that a certain degree
      of hydrophobicity may be necessary for the groups attached to the literal metal
      bonding structure if the compounds are to successfully inhibit the epimastigotes
      of Trypanosoma cruzi. The development of antiprotozoal drugs which are chelating
      agents specifically designed to selectively disrupt the essential metal
      metabolism of Trypanosoma cruzi should furnish a new generation of drugs which
      can be used in the treatment of Chagas' disease.

PMID- 8530924
TI  - The brain in obsessive-compulsive disorder.

PMID- 8530926
TI  - Rosa canina (dog rose).

PMID- 8530927
TI  - Micrographia in Chinese characters.

PMID- 8530925
TI  - Diagnosis of inherited metabolic disorders affecting the nervous system.
AB  - Knowledge of the molecular causes for genetic diseases that affect the nervous
      system is rapidly expanding. Especially striking has been the finding in several
      autosomal dominant neurodegenerative disorders that unstable expansions of
      trinucleotide repeats are responsible for the genetic disorder and that the
      length of the repeat can be correlated with the age of onset and the severity of
      symptoms. Phenotypic heterogeneity in many disorders associated with enzyme
      deficiencies can often be linked to the amount of residual enzyme activity
      occurring with different gene mutations. Making a specific diagnosis of a
      neurological disorder associated with genetically determined metabolic defects
      requires access to a laboratory that can assist in arranging for appropriate
      testing to be carried out. In some disorders such as the aminoacidurias
      diagnostic metabolic studies can be performed in hospital clinical chemistry
      laboratories. In others, such as the lysosomal storage diseases, a laboratory
      that carries out special lipid analyses and white blood cell enzyme assays will
      be necessary. DNA mutational analyses are becoming commercially available for
      diagnosing many disorders such as mitochondrial diseases and those conditions
      associated with expanded trinucleotide repeats. It may be necessary to contact
      individual research laboratories when confronted with a disorder that has been
      newly discovered or that is very rare. A computerised directory of specialised
      laboratories that perform disease specific testing for genetic disorders should
      be useful in choosing the appropriate diagnostic or research laboratory.

PMID- 8530928
TI  - Visual vertigo syndrome: clinical and posturography findings.
AB  - Neuro-otological and posturography findings in 15 patients with visually induced
      vertiginous symptoms (visual vertigo) are reported. Thirteen patients were
      considered to have a peripheral vestibular disorder; seven had abnormal caloric
      or rotational test results. Two patients had CNS disorder--a cerebellar
      degeneration and a brainstem stroke. Posturography testing showed that five
      patients showed abnormally large body sway induced by full field visual motion
      stimulation. This group included the two patients with CNS disease and four with
      strabismic symptoms (diplopia, squint surgery, and ocular muscle weakness). It is
      concluded that visual vertigo is a heterogeneous syndrome with peripheral or
      central aetiologies and may occur if patients with balance disorders show high
      visual field dependence. In patients with visual vertigo, the presence of
      additional CNS or strabismic symptoms may cause inappropriate postural reactions
      in environments with conflicting or disorienting visual stimuli, probably by
      reducing the ability to resolve the sensory conflict.

PMID- 8530929
TI  - Withdrawal of antiepileptic drug treatment in childhood epilepsy: factors related
      to age.
AB  - The clinical and electroencephalographic changes with age were evaluated in 304
      patients with childhood epilepsies, whose antiepileptic treatment had been
      discontinued after a seizure free period of more than three years. The withdrawal
      rate differed significantly between epileptic syndromes, being higher in
      idiopathic epilepsy and lower in symptomatic epilepsy. The age at withdrawal was
      characteristic for each epileptic syndrome, and generally showed two peaks: at
      preadolescence and early school age. Forty one (13.5%) of the 304 patients
      experienced relapses. The relapse rate differed between epileptic syndromes.
      Relapses occurred at a unique age in each epileptic syndrome, and were frequent
      in preadolescence and early adulthood. Electroencephalography that still showed
      paroxysmal discharges at withdrawal did not necessarily predict the occurrence of
      a relapse, but the changes in background activity with age, which may indicate
      maturation of the CNS, were significantly different between the patients with and
      those without relapses. The results suggest that age related to each epileptic
      syndrome should be considered when deciding on withdrawal of antiepileptic drugs.

PMID- 8530930
TI  - Electrodiagnostic criteria for polyneuropathy and demyelination: application in
      135 patients with Guillain-Barre syndrome. Dutch Guillain-Barre Study Group.
AB  - Since the development of effective but expensive therapeutic strategies for the
      treatment of Guillain-Barre syndrome, early confirmation of the diagnosis has
      become very important. Electrodiagnostic criteria were developed for the
      discrimination of polyneuropathy and in particular for demyelination. The
      sensitivity and specificity of these criteria were determined in 135 patients
      with Guillain-Barre syndrome in an early stage of the disease, along with 45
      healthy volunteers. The algorithms used to develop our criteria consisted of sets
      of selected electrodiagnostic variables, each of them relevant to the detection
      of polyneuropathy. Each set was applied on all of three consecutive
      electrodiagnostic examinations within one month of disease onset. Application of
      the best set resulted in 85% of patients with Guillain-Barre syndrome fulfilling
      the criteria for polyneuropathy at the first examination (mean time interval six
      days of disease onset), whereas none of the healthy volunteers fulfilled the
      criteria (sensitivity 85%, specificity 100%). The set of criteria for the
      detection of demyelination was fulfilled by 60% during the first examination (by
      66% and 72% during the second and third examination). Application of criteria for
      demyelinating polyneuropathy as defined by others resulted in substantially
      lowered incidence (3%-46%). It is concluded that these criteria for the
      electrodiagnostic delineation of polyneuropathy are the most sensitive to date,
      with respect to the early confirmation of the diagnosis of Guillain-Barre
      syndrome.

PMID- 8530931
TI  - Migraine.

PMID- 8530932
TI  - Magnetisation transfer ratios and transverse magnetisation decay curves in optic
      neuritis: correlation with clinical findings and electrophysiology.
AB  - Conventional MRI sequences do not permit the distinction between the different
      pathological characteristics (oedema, demyelination, gliosis, axonal loss) of the
      multiple sclerosis plaque. Magnetisation transfer imaging and transverse
      magnetisation decay curve (tMDC) analysis may be more specific. These techniques
      have been applied to the optic nerves in 20 patients with optic neuritis and the
      results correlated with clinical and visual evoked potential (VEP) findings. tMDC
      analysis failed to identify separate intracellular and extracellular water
      compartments within the optic nerve but gave a measure of transverse relaxation
      time (T2) without the confounding effects of CSF in the nerve sheath. Both T2 and
      magnetisation transfer ratio (MTR) were abnormal after an episode of optic
      neuritis. T2 did not correlate with visual function or with VEP latency or
      amplitude. There was a significant correlation between MTR reduction and
      prolongation of VEP latency: this increased latency may reflect an effect of
      myelin loss on MTR. Longer lesions were associated with worse visual outcome,
      implying that the overall extent of pathological involvement is likely to
      influence the degree of functional deficit.

PMID- 8530933
TI  - Changes in the balance between motor cortical excitation and inhibition in focal,
      task specific dystonia.
AB  - Transcranial magnetic stimulation has been used in a double pulse paradigm to
      investigate the excitability of intrinsic motor cortical circuits in 15 patients
      with focal task specific dystonia of the right hand and a group of eight age
      matched controls. The left hemisphere was examined in five patients; in the
      remainder, both hemispheres were tested. There was no significant difference in
      stimulation threshold between patients and controls nor between the left and
      right hemispheres in the patients. There was a significant decrease in early
      corticocortical suppression when comparing stimulation of the left hemisphere in
      the patients and controls at interstimulus intervals of 1-15 ms (P < 0.01). There
      was no difference in the amount of suppression in the right and left hemispheres
      of the patients. It is concluded that in focal task specific dystonia there is
      shift in the balance between excitation and inhibition in local circuits of the
      motor cortex which leads to a net decrease in the amount of short latency
      suppression. These changes reflect disturbed basal ganglia input to the motor
      cortex. Reduced excitability of cortical inhibitory circuits may be one factor
      which contributes to the excessive and inappropriate muscle contraction which
      occurs during fine motor tasks in patients with focal dystonia.

PMID- 8530934
TI  - Abnormal refractoriness in patients with Parkinson's disease after brief
      withdrawal of levodopa treatment.
AB  - Two pairwise matched groups of patients with mild to moderate Parkinson's disease
      and a group of normal age matched controls were used to investigate the effects
      on simple and choice reaction time (RT) of brief withdrawal of levodopa therapy.
      Comparisons within and across these groups disclosed a selective effect of
      levodopa withdrawal. After about 12 hours of levodopa deprivation, patients
      exhibited an exaggeration of normal refractoriness, the well established tendency
      for RT to increase progressively as the delay between a response and the next
      imperative signal is reduced below 0.5 s. Increased refractoriness was at least
      as great for simple as choice RT. Choice RT on trials involving repetition (as
      opposed to alternation) of the previous response, however, showed no tendency
      towards greater impairment by brevity of the recovery period or by withdrawal of
      medication, eliminating an effector based account. With longer recovery periods,
      RT was unaffected by medication; indeed, unmedicated patients were as fast as
      normal subjects under these conditions. Even at the briefest delays, fully
      medicated patients did not differ from normal controls. The paper concludes with
      a critical review of chronometric studies of medication effects in Parkinson's
      disease.

PMID- 8530935
TI  - A community based study of the incidence of dementia in subjects aged 85 years
      and over.
AB  - The aim was to investigate the incidence rate of dementia for community residents
      aged 85 years and over. It was a two wave community study of 224 subjects
      (community residents including those residing in a nursing home) older than 85
      years, restudied 4.1 years after a community prevalence study. A two stage method
      was used, comprising the mini mental state examination followed in a stratified
      sample by the geriatric mental state schedule (A3)/AGECAT. Incidence rates were
      based on person-years at risk. The overall incidence of dementia was 6.9 (95%
      confidence interval (95% CI) 4.8-9.1) per 100 person-years at risk. The incidence
      was significantly higher for women than for men; respectively 8.9 (95% CI 5.9
      11.9) v 2.7 (95% CI 0.5-4.9) per 100 person-years at risk. In the fastest growing
      age group seven out of 100 persons develop dementia each year. Women, who
      constitute two thirds of the oldest old, seem to have a higher risk. Further
      research is needed into the risk factors for dementia in this age group.

PMID- 8530936
TI  - Spontaneous intracranial hypotension.
AB  - The clinical features and radiological appearances of spontaneous intracranial
      hypotension are described in three patients and the medical literature is
      reviewed. Awareness of this condition and its differentiation from more sinister
      meningitic processes is important to avoid unnecessary invasive investigations
      and to allow prompt diagnosis and effective treatment.

PMID- 8530937
TI  - Spontaneous intracranial hypotension from a CSF leak in a patient with Marfan's
      syndrome.
AB  - A patient with Marfan's syndrome had spontaneous intracranial hypotension
      secondary to a proved CSF leak. It is postulated that the leak was caused by
      minor, unrecognised trauma rupturing spinal arachnoid diverticula. The
      diverticula were probably pre-existing abnormalities complicating the Marfan's
      syndrome. It is concluded that patients with spinal meningeal defects may be at
      increased risk of developing CSF leaks, possibly secondary to unrecognised
      trauma.

PMID- 8530938
TI  - Early and severe sensory loss in three adult siblings with hexosaminidase A and B
      deficiency (Sandhoff disease).
AB  - Three siblings in their sixth and seventh decade with hexosaminidase A and B
      deficiency (adult form of GM2-gangliosidosis, variant O) developed early and
      severe sensory loss in addition to chronic motor neuron disease and cerebellar
      ataxia. Prominent mechanoallodynia was a manifesting symptom in two siblings. It
      is suggested that sensory deficits are due to a central-peripheral dying back
      axonopathy. The early and dominant sensory disturbances extend the clinical range
      of GM2-gangliosidosis.

PMID- 8530939
TI  - Serial MRI in listeria mesenrhombencephalitis: a case report.
AB  - Listeria mesenrhombencephalitis is a rare disorder, especially in the non
      immunocompromised host. The predilection for brain stem involvement is
      unexplained. The anatomical correlation of brain stem signs with serial MRI over
      three months is shown in a 64 year old white man. The pathological lesions seemed
      to be a combination of micro-abscesses and associated oedema.

PMID- 8530940
TI  - Is the frequency of multiple sclerosis increasing in Mexico?
AB  - Multiple sclerosis has steadily increased in Mexican mestizos from an apparently
      rare disorder in the 1970s to the second most frequent cause of admission to a
      neurology ward in the 1990s. Most patients belonged to high socioeconomic and
      educational groups. Familial incidence was low. Age at onset was younger than in
      other series and long term disability was milder than in patients from countries
      in which the disease is apparently more prevalent.

PMID- 8530941
TI  - Parietal kinetic ataxia without proprioceptive deficit.
AB  - A patient with acute onset "classic" cerebellar ataxia of the right arm without
      clinically detectable deep sensory loss is reported, in relation to an acute
      posterior parietal infarct. Wild back and forth swaying of the arm, giving away,
      or worsening by suppression of vision were not seen. The lesion involved area 5,
      parts of area 7, the angular gyrus, the middle and posterior parieto-occipital
      gyri, and posterior parts of the superior and middle temporal gyri. The
      paracentral lobule, commonly thought to be responsible for parietal ataxia, was
      spared. Thus posterior parietal lesions can mimick cerebellar ataxia, possibly by
      severing specific projections to the ventrolateral thalamic nuclei. On the basis
      of previous studies in primates, the superior parietal gyrus may play a major
      part in the ataxia presented by this patient.

PMID- 8530942
TI  - Extinction during time controlled direct retinal stimulation after recovery from
      right hemispheric stroke.
AB  - The temporal variables of extinction in two patients with right hemispheric
      stroke and two normal controls were studied using a scanning laser ophthalmoscope
      (SLO). This instrument enabled eye movements to be controlled for by projecting
      time controlled stimuli directly on to the retina. Both patients had recovered
      from their stroke (four months and five years) and seemed clinically normal. At
      50 ms, patient 1 extinguished one of two stimuli on seven of 40 double
      simultaneous stimulation (DSS) trials (five left, two right) and patient 2
      extinguished the left stimulus on every DSS trial. At 100 ms, patient 1 performed
      almost perfectly, whereas patient 2 extinguished on 30% of the DSS trials (10
      left, two right). At 200 ms, patient 2 performed perfectly. Neither of the
      controls showed extinction to DSS at any presentation time. Thus detecting DSS
      was time dependent in the patients but not the normal subjects. These data
      support the theory that recovery from neglect after right hemispheric damage may
      be mediated by the left hemisphere.

PMID- 8530943
TI  - Spiral computed tomography angiography in the assessment of middle cerebral
      artery occlusive disease.
AB  - There has been no report on the use of spiral computed tomography angiography
      (CTA) in the investigation of intracranial cerebral artery stenosis. A
      prospective pilot study was conducted to investigate the feasibility of CTA in
      the diagnosis of intracranial occlusive disease and its correlation with
      transcranial Doppler. With transcranial Doppler, 10 patients with acute ischaemic
      stroke with middle cerebral artery stenosis or occlusion were identified. There
      were seven middle cerebral artery stenoses and five middle cerebral artery
      occlusions. The CTA confirmed all diagnoses by transcranial Doppler except in one
      patient with middle cerebral artery occlusion in whom the embolus had probably
      propagated. The results showed that CTA is feasible and potentially useful in the
      diagnosis of middle cerebral artery occlusive disease. Further studies are
      required to assess its validity, sensitivity, and specificity in the diagnosis of
      middle cerebral artery occlusive disease.

PMID- 8530944
TI  - Comparison of triple dose versus standard dose gadolinium-DTPA for detection of
      MRI enhancing lesions in patients with primary progressive multiple sclerosis.
AB  - This study was performed to evaluate whether a triple dose of gadolinium-DTPA (Gd
      DTPA) increases the sensitivity of brain MRI for detecting enhancing lesions in
      patients with primary progressive multiple sclerosis (PPMS). T1 weighted brain
      MRI was obtained for 10 patients with PPMS in two sessions. In the first session,
      one scan was obtained five to seven minutes after the injection of 0.1 mmol/kg Gd
      DTPA (standard dose). In the second session, six to 24 hours later, one scan
      before and two scans five to seven minutes and one hour after the injection of
      0.3 mmol/kg Gd-DTPA (triple dose) were obtained. Four enhancing lesions were
      detected in two patients when the standard dose of Gd-DTPA was used. The numbers
      of enhancing lesions increased to 13 and the numbers of patients with such
      lesions to five when the triple dose of Gd-DTPA was used and to 14 and six in the
      one hour delayed scans. The mean contrast ratio for enhancing lesions detected
      with the triple dose of Gd-DTPA was higher than those for lesions present in both
      the standard dose (P < 0.0009) and the one hour delayed scans (P = 0.04). These
      data indicate that with a triple dose of Gd-DTPA many more enhancing lesions can
      be detected in patients with PPMS. This is important both for planning clinical
      trials and for detecting the presence of inflammation in vivo in the lesions of
      such patients.

PMID- 8530945
TI  - The role of imaging in the follow up of meningiomas.
AB  - A retrospective study of 60 patients with meningiomas was conducted to evaluate
      the role of imaging in postoperative follow up. Using case notes and imaging
      studies, requests were assessed with reference to the indications for imaging
      radiological findings and effect on patient management. Patients were divided
      into three groups: 34 who had undergone a macroscopically complete resection, 18
      with known residual tumour, and eight in whom surgery was not performed. These 60
      patients underwent a total of 165 CT and 11 MRI studies. In the complete
      resection group only two patients developed a recurrence, both having highly
      suggestive symptoms or signs. It is concluded that routine imaging is not
      indicated in asymptomatic patients after complete tumour clearance. Both CT and
      MRI contribute to patient management in those with residual disease, MRI probably
      being the imaging method of choice.

PMID- 8530946
TI  - Callosal disconnection syndrome and knowledge of the body: a case of left hand
      isolation from the body schema with names.
AB  - A patient is described who presented with a disturbance of body cognition
      confined to the left side of the body. She showed difficulties in naming the left
      fingers and in moving the named left fingers. She also showed great difficulty in
      pointing to named parts of the body with her left hand. Earlier in the course of
      the disease she showed a personification phenomenon of the left hand. Brain MRI
      showed involvement of the entire corpus callosum, probably due to occlusion of a
      branch of the anterior cerebral artery. It is speculated that this syndrome is
      caused by disconnection of the right hemisphere from the left hemispheric body
      schema.

PMID- 8530947
TI  - Sporadic lower limb hypertrophy and exercise induced myalgia in a woman with
      dystrophin gene deletion.
AB  - A 25 year old woman, without family history of muscular dystrophy, had had an
      isolated lower limb hypertrophy since infancy and later experienced exercise
      induced myalgia. Genomic DNA analysis showed a deletion of exons 45 to 52 of the
      dystrophin gene. Uncommon phenotypes of dystrophinopathies and consequences in
      genetic counselling in women are emphasised.

PMID- 8530948
TI  - A simple model to explain the motor fluctuations seen in Parkinson's disease.

PMID- 8530949
TI  - Severe intraventricular haemorrhage shown by computed tomography as an unusual
      manifestation of Wernicke's encephalopathy.

PMID- 8530950
TI  - Neuromyotonia in association with malignant hyperpyrexia.

PMID- 8530951
TI  - Arg296 to Cys296 polymorphism in exon 6 of cytochrome P-450-2D6 (CYP2D6) is not
      associated with multiple system atrophy.

PMID- 8530952
TI  - Ataxic hemiparesis with bilateral leg ataxia from pontine infarct.

PMID- 8530953
TI  - Autoimmune chronic active hepatitis and polymyositis in a patient with myasthenia
      gravis and thymoma.

PMID- 8530954
TI  - Transient monocular blindness.

PMID- 8530955
TI  - Acquired bilateral opercular lesions or Foix-Chavany-Marie syndrome and eating
      epilepsy.

PMID- 8530956
TI  - HTLV 1 associated myelopathy and adult T cell leukaemia-lymphoma in the same
      patient: report of a case.

PMID- 8530957
TI  - Magnetic resonance spectroscopic study of parkinsonism related to boxing.

PMID- 8530958
TI  - Treatment of chronic limb spasticity with botulinum toxin A.

PMID- 8530959
TI  - Vascular ataxic hemiparesis: a reevaluation.

PMID- 8530960
TI  - Do musical hallucinations have a neurological cause?

PMID- 8530961
TI  - Dissociation, fractionation and culture of chick embryo sympathetic ganglionic
      cells.

PMID- 8530962
TI  - Evidence for a correlation between myelin period and number of myelin lamellae in
      fibres of the feline spinal cord white matter.

PMID- 8530963
TI  - The effects of injection of potassium cyanide into the sciatic nerve of the adult
      mouse: in vivo and electron microscopic studies.

PMID- 8530964
TI  - Synaptic contacts from nodes of Ranvier in the granular layer of the frog
      cerebellum.

PMID- 8530965
TI  - Ultrastructural changes in isoniazid-induced brain oedema in the dog.

PMID- 8530966
TI  - Elongated profiles of synaptic vesicles in motor endplates. Morphological effects
      of fixative variations.

PMID- 8530967
TI  - The fate of synaptic membranes of degenerating optic nerve terminals, and their
      role in the mechanism of trans-synaptic changes.

PMID- 8530968
TI  - Organelle formation from pinocytotic elements in neurites of cultured sympathetic
      ganglia.

PMID- 8530969
TI  - Innervation of the intestinal muscular coat.

PMID- 8530970
TI  - Are the coats of coated vesicles artefacts?

PMID- 8530971
TI  - The surface coats of chick dorsal root ganglion cells in vitro.

PMID- 8530972
TI  - An electron microscopic investigation of glycogen and mitochondria in developing
      and adult rat spinal motor neuropil.

PMID- 8530973
TI  - Observations on oligodendrocyte degeneration, the resolution of status spongiosus
      and remyelination in cuprizone intoxication in mice.

PMID- 8530974
TI  - Alzheimer-type pathology in melanin-bleached sections of substantia nigra.
AB  - Bleaching of melanin prior to Gallyas staining enabled us to detect an
      unexpectedly large number of neurofibrillary tangles (NFTs; 62 and 50 NFTs in the
      upper and the lower substantia nigra, respectively, mostly in the neuronal
      cytoplasm of the medial zona compacta) in brains of patients who had had
      Alzheimer's disease. Amyloid-like deposits were quite scarce. In Alzheimer's
      disease it has been commonly observed that other subcortical nuclei projecting
      widely to the cerebral cortex also contain a large number of NFTs, although they
      have few amyloid deposits. In these subcortical nuclei retrograde degeneration
      may initially affect intraneuronal processes, leading to the preferential
      development of NFTs in the neuronal cytoplasm.

PMID- 8530975
TI  - Sequence analysis of mitochondrial DNA in a new maternally inherited
      encephalomyopathy.
AB  - A heteroplasmic insertion of a 9-bp tandem repeat element was detected in the
      mitochondrial DNA of the maternal members of a large family. The mutation was
      contained within the non-coding region between the genes specifying subunit II of
      cytochrome c oxidase and tR-NA(Lys). The proband and most of his maternal
      relatives were affected by a late-onset mitochondrial encephalomyopathy of
      variable severity, characterized by a unique combination of symptoms. Extensive
      screening of a large series of DNA samples, collected from unrelated normal
      individuals as well as patients affected by different neurological disorders,
      consistently failed to detect the 9-bp insertion, with two exceptions: a patient
      suffering from a syndrome virtually identical to that described in our original
      family and a child affected by bilateral striatal necrosis, a disorder which has
      been attributed to impairment of mitochondrial oxidative phosphorylation. These
      considerations suggest that the 9-bp insertion is pathogenic and that the region
      affected by the mutation may play a previously unsuspected functional role in
      mtDNA gene expression.

PMID- 8530977
TI  - Selective peripheral denervation for spasmodic torticollis: is the outcome
      predictable?
AB  - If botulinum toxin fails in the treatment of cervical dystonia, selective
      peripheral denervation is now accepted as the best surgical option. Despite the
      very promising results, however, there is still a substantial group of patients
      who do not benefit from this procedure. Positive response to prior botulinum
      toxin therapy seems to be a very good predictor of outcome after selective
      peripheral denervation (P < 0.01). The meaning of the histological findings of
      the resected nerves is uncertain. Patients with histologically proven
      pathological nerves do not seem to benefit more than patients with histological
      normal ones (P < 0.30).

PMID- 8530976
TI  - Acute myelopathy of unknown aetiology: a clinical, neurophysiological and MRI
      study of short- and long-term prognostic factors.
AB  - Brain and spinal cord magnetic resonance imaging (MRI), multimodal evoked
      potentials (EPs) and cerebrospinal fluid (CSF) analysis were performed in 27
      patients with acute myelopathy of unknown aetiology (AMUA), to detect the
      diagnostic and prognostic values of paraclinical tests at presentation. Spinal
      cord MRI was abnormal in 56% and brain MRI in 33% of the patients. Visual EPs
      were abnormal in 7%, median somatosensory EPs in 17%, tibial somatosensory EPs in
      56% and motor EPs in 35% of the cases examined. Brain-stem acoustic EPs were
      normal in all the patients. CSF oligoclonal bands (OBs) were detected in 30% of
      cases. The patients were divided into subgroups according to the short-term
      clinical outcome (complete, partial or absent recovery). There were no
      significant differences among the three groups as regards MRI findings. Patients
      with complete recovery showed a significantly lower frequency of tibial
      somatosensory EP and motor EP abnormalities. According to the paraclinical
      findings at onset and on the basis of a long-term clinical follow-up (mean
      duration 24 months), 6 patients were diagnosed as having clinically definite
      multiple sclerosis, while 21 did not develop further neurological disturbances.
      Only the presence of CSF OBs was significantly more frequent in patients with
      definite multiple sclerosis. Our study indicates that EPs exploring spinal cord
      function are more powerful than spinal MRI for predicting the short-term outcome
      of AMUA, while the combined use of brain MRI and CSF OBs has the highest negative
      predictive value for the subsequent development of clinically definite multiple
      sclerosis.

PMID- 8530978
TI  - A genetic study of idiopathic focal dystonias.
AB  - The inheritance of focal dystonias was investigated in 43 families containing 43
      index cases with torticollis (n = 21), blepharospasm (n = 18) and writer's cramp
      (n = 4). They generated a potential population of 235 first-degree relatives, and
      168 out of 179 living first-degree relatives were examined. Ten relatives with
      dystonia were identified in ten families. Another two parents from two of the
      same group of ten families were affected according to the family history. The
      majority of the secondary cases (six patients, five siblings, and one child) were
      not aware of any dystonia. The tendency for affected relatives to have the same
      type of dystonia as index patients was observed only for torticollis. Overall,
      23% of index patients had relatives with dystonia. Segregation analysis suggested
      the presence of an autosomal dominant gene or genes with reduced penetrance
      underlying focal dystonia.

PMID- 8530979
TI  - Dementia of frontal lobe type due to adult polyglucosan body disease.
AB  - We describe a patient with adult polyglucosan body disease (APBD) who presented
      with a dementia of frontal lobe type (FLD), with a neurogenic bladder but no
      symptoms of sensory motor peripheral neuropathy. Diagnosis was made from a
      cerebral biopsy specimen which showed an accumulation of intra-axonal
      polyglucosan bodies in the central nervous system. This case differs from the
      usual presentation, in which gait disturbance is the main symptom and diagnosis
      is possible by sural nerve biopsy. Little is known about the neuropsychological
      pattern of APBD dementia but FLD has not previously been described. APBD is a
      heterogeneous clinical entity of unknown cause. This diagnosis must be considered
      in elderly patients with dementia.

PMID- 8530980
TI  - Fixation instability and oculomotor abnormalities in Friedreich's ataxia.
AB  - Eye movements were studied in 13 patients with Friedreich's ataxia and correlated
      with MRI findings to investigate whether oculomotor abnormalities can be traced
      to cerebellar disturbances in this disease. One of the most prominent eye signs
      was fixation instability (square-wave jerks, SWJ.). Besides SWJ the patients
      showed various combinations of cerebellar, vestibular and brain-stem oculomotor
      signs. Our patients did not comprise a homogeneous group with regard to their
      oculomotor findings. There was no correlation between the severity of any of the
      so-called cerebellar oculomotor disturbances and the number of SWJ. We tried to
      correlate the extent of oculomotor disturbances with floccular atrophy and
      atrophy of the dorsal vermis on MRI in seven of the patients. None of the
      oculomotor features (including SWJ) correlated with flocculus or dorsal vermis
      size. Furthermore, floccular and vermal measurements on MRI were normal.
      Accordingly, we think it unlikely that the oculomotor disturbances, including
      SWJ, are attributable to cerebellar pathology per se.

PMID- 8530981
TI  - Proton magnetic resonance spectroscopy of systemic lupus erythematosus involving
      the central nervous system.
AB  - We examined 13 patients with neurological manifestations of systemic lupus
      erythematosus (SLE) based on previous and/or current neurological or psychotic
      episodes by magnetic resonance imaging (MRI) and proton magnetic resonance
      spectroscopy (MRS) together with psychiatric and cognitive assessment. MRI was
      abnormal in 7 patients, showing high signal lesions in the white matter and/or
      cerebral atrophy. Proton MRS centred on white matter lesions in 5 patients showed
      a reduction in the N-acetyl aspartate creatine ratio compared with normal
      appearing white matter in the SLE group and in 10 healthy controls. This pattern
      of abnormality does not allow differentiation of SLE lesions from the chronic
      plaques occurring in multiple sclerosis. There was a very high incidence of
      current psychiatric morbidity in the SLE group, namely in 12 of the 13 patients.
      There was no correlation between the presence of current psychiatric involvement
      and/or cognitive dysfunction and abnormalities detected with MRI or MRS.

PMID- 8530982
TI  - Botulinum toxin in cervical dystonia: low dosage with electromyographic guidance.
AB  - Sixty patients with idiopathic cervical dystonia were treated a total of 240
      times with botulinum toxin type A (BTA). Selected muscles were injected with BTA
      under electromyographic (EMG) guidance. The clinical effect was measured on the
      Tsui scale and a 10-point anchored visual analogue scale. A dosage of 150-300
      mouse units was used in 77% of the treatments (mean 204 mouse units). Based on
      the Tsui scale, 45% of 240 treatments were still effective at the moment of
      reinjection (median improvement 2 points). Based on the 10-point anchored visual
      analogue scale, 73% of treatments were successful (median improvement 3 points).
      Forty-eight patients (80%) responded favourably to the treatment. Side-effects
      were mild and transient. Dysphagia occurred in 9% of treatments. Antibody
      production was investigated in 41 patients and was negative in all. A striking
      difference from previous reports is the lower dosage used in this study. The
      clinical response, however, was similar to that of other studies. We conclude
      that a dosage of 200-400 mouse units BTA (Dysport) may also be effective in the
      treatment of cervical dystonia, but with fewer side effects. EMG guidance and
      application of BTA into deep cervical muscles may further improve the clinical
      effect.

PMID- 8530983
TI  - Progression of motor and cognitive impairment in Parkinson's disease.
AB  - We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor
      and mental deterioration in patients with Parkinson's disease. Of the original 91
      patients, only 61 could be re-examined 7 years later and 11 of these had become
      demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive
      performance than non-demented parkinsonian patients (PDs). A global cognitive
      decay index (DI) was calculated for each patient. Based on this, non-demented PDs
      were further split into 38 stable parkinsonian patients (S-PDs) with DI-30% to
      +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a
      DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor
      impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs
      and PD-Dems deteriorated especially in attention, visuospatial and executive
      ability tests. Ageing seems to be the main predictive factor for mental
      deterioration.

PMID- 8530984
TI  - Atypical motor neuron disease with severe ophthalmoloplegia: a report of two
      cases.

PMID- 8530985
TI  - Treatment of a sublingual hematoma with medicinal leeches: report of case.

PMID- 8530986
TI  - Osteomeatal complex obstruction and sinusitis following Le Fort I osteotomy.

PMID- 8530987
TI  - Mandible fracture in a child with Menkes' kinky hair syndrome.

PMID- 8530988
TI  - Odontogenic ghost cell carcinoma: report of a case and review of the literature.

PMID- 8530989
TI  - Squamous cell carcinoma in the maxilla probably originating from a nasopalatine
      duct cyst: report of case.

PMID- 8530990
TI  - Pathologic mandibular fracture associated with familial dysautonomia.

PMID- 8530991
TI  - Juvenile xanthogranuloma: report of case.

PMID- 8530992
TI  - Concerns about our association.

PMID- 8530993
TI  - Histologic and microradiologic comparison of block and particulate cancellous
      bone and marrow grafts in reconstructed mandibles being considered for dental
      implant placement.
AB  - PURPOSE: Patterns of healing were investigated in mandibles reconstructed with
      three different techniques to assess their readiness for implant placement.
      PATIENTS AND METHODS: The subjects were 10 patients who had undergone mandibular
      reconstruction with either nonvascularized iliac block bone grafts (group 1; 3
      patients), particulate cancellous bone and marrow (PCBM) grafts (group 2; 3
      patients) for mandibular discontinuity, or PCBM grafts for mandibular marginal
      defects (group 3; 4 patients). Six (groups 2 and 3) or 12 months (group 1) after
      mandibular reconstruction, bone biopsy specimens were obtained for histologic
      examination with a trephine bur. As controls, bone specimens were obtained from
      ungrafted mandibles of patients undergoing dental implant placement.
      Undecalcified specimens were embedded in polyester resin and examined by routine
      light microscopy and microradiography. RESULTS: The morphology of the specimens
      from group 1 was similar to that of group 2, but not to that of the control
      subjects. However, the morphology of specimens from group 3 was generally similar
      to that of control subjects. CONCLUSION: These results suggest that mandibular
      reconstruction with PCBM grafts allows the placement of dental implants sooner
      than reconstruction with block bone grafts.

PMID- 8530994
TI  - Preliminary study of low-level laser for treatment of long-standing sensory
      aberrations in the inferior alveolar nerve.
AB  - PURPOSE: The incidence of inferior alveolar nerve (IAN) damage during removal of
      third molar teeth has been reported to be as high as 5.5% and up to 100% during
      sagittal split osteotomy. Sensory aberrations in the IAN persisting for longer
      than 6 months leave some degree of permanent disability. The purpose of this
      double-blind, clinical trial was to examine the effects of low-level laser (LLL)
      treatment using a GaAIAs laser (820 nm, Ronvig, Denmark) on touch and temperature
      sensory perception after a long-standing postsurgical IAN injury. PATIENTS AND
      METHODS: Thirteen patients were divided into two groups, one of which received
      real LLL (4 x 6 J per treatment along the distribution of the IAN to a total of
      20 treatments) and the other placebo LLL. The degree of mechanoreceptor injury as
      assessed by Semmes Weinstein Monofilaments (North Coast Medical, San Jose, CA)
      were comparable in the two groups before treatment. The degree of thermal
      sensitivity disability as assessed using a Thermotester (Somedic AB, Stockholm,
      Sweden) to examine the indifferent temperature threshold was also comparable
      between the two groups before LLL. RESULTS: Subsequent to LLL, the real laser
      treated group showed a significant improvement in mechanoreceptor sensory testing
      (P = .01) compared with the placebo group, as manifested by a decrease in load
      threshold (g) necessary to elicit a response from the most damaged area. In
      addition, the real LLL group reported a subjective improvement in sensory
      function. There was no significant improvement in thermal sensitivity post-LLL
      for either the real or placebo laser-treated groups. CONCLUSION: It was concluded
      that LLL can improve mechanoreceptor perception in long-standing sensory
      aberrations in the IAN.

PMID- 8530995
TI  - Blood loss and transfusion requirements in orthognatic surgery.
AB  - PURPOSE: This study quantified the blood loss and transfusion requirements in
      orthognathic surgery. PATIENTS AND METHODS: Three hundred sixty consecutive
      healthy orthognathic surgery patients were included in this retrospective study.
      The female:male ratio was 1.8:1, and the age range was 8 to 49 years (mean, 24).
      Estimated blood volume (EBV), estimated blood loss (EBL), and transfused blood
      were calculated. RESULTS: EBL ranged from 50 to 5,000 mL (mean, 600) representing
      up to 73% of EBV (mean, 16%). In total, 24% (84 patients) were transfused, 8.7%
      (6 patients) after single-jaw surgery and iliac bone harvest and 26.7% (78
      patients) after bimaxillary osteotomies. Forty-seven patients received 1 unit of
      transfused blood, 25 patients had 2 units, and 12 patients had more than 2 units.
      Most transfused patients lost 11% to 40% of EBV. CONCLUSIONS: Transfusion is not
      necessary for single-jaw surgery unless a bicoronal flap or iliac bone harvest
      are required. Although only 27% of bimaxillary osteotomy patients required
      transfusion of 1 to 2 units, this group was not predictable based on the type of
      procedure involved, and a further subgroup (4% of the 291 patients) required a
      larger transfusion.

PMID- 8530996
TI  - Oral surgery in anticoagulated patients without reducing the dose of oral
      anticoagulant: a prospective randomized study.
AB  - PURPOSE: This study assessed the risk associated with several schedules of
      perioperative treatment with coumadin in anticoagulated patients who underwent
      oral surgery. PATIENTS AND METHODS: A prospective, randomized study compared
      bleeding complications with six perioperative schedules in 92 patients
      chronically treated with acenocoumarol. In three of the perioperative schedules,
      the dose was reduced before surgery and calcium heparin was added. In the other
      three, oral anticoagulation was not modified and heparin was not used. The groups
      also differed regarding the antifibrinolytic agents used and the postoperative
      measures applied. RESULTS: Those schedules in which the oral anticoagulation was
      not modified preoperatively and an antifibrinolytic agent was applied locally
      both during and after surgery were not associated with a significantly higher
      odds ratio of bleeding complications than those in whom oral anticoagulation was
      reduced and calcium heparin was added preoperatively. CONCLUSIONS: In orally
      anticoagulated patients who undergo oral surgery, schedules that maintain the
      oral anticoagulant regimen and use local tranexamic acid as an antifibrinolytic
      agent postoperatively for 2 days are safe, simple, and less troublesome.

PMID- 8530997
TI  - A study of orofacial tumors in Nigerian children.
AB  - PURPOSE: This study evaluated the type and distribution of tumors in the
      orofacial tissues of black African children. PATIENTS AND METHODS: The hospital
      records of all patients aged 15 years or younger, who presented at the Lagos
      University Teaching Hospital (a tertiary referral center) with a histologically
      confirmed orofacial tumor over a 13-year period were analyzed. RESULTS: One-fifth
      of all orofacial tumors during the study period occurred in the pediatric age
      group. The male-female ratio was 1.4 to 1 and 11- to 15-year-olds were most
      frequently affected. Benign tumors (59.8%) were more prevalent than malignant
      tumors (40.2%). Overall, 18.4% of the tumors were of odontogenic origin, 42.5%
      were benign nonodontogenic tumors, and 39.1% were malignant nonodontogenic
      tumors. The anterior part of the mandible was frequently involved by
      ameloblastoma, which was the most common odontogenic tumor (6.3%). Most of the
      benign nonodontogenic tumors were of mesenchymal origin (46%), and most were
      located in soft tissues (59.5%). Burkitt's lymphoma (22.4%) was the most common
      malignant nonodontogenic tumor. CONCLUSION: The observed differences in tumor
      type and distribution in this study compared with previous studies may be
      attributable to genetic and geographic differences in the populations studied.

PMID- 8530998
TI  - Analysis of facial and trigeminal nerve function after arthroscopic surgery of
      the temporomandibular joint.
AB  - PURPOSE: This study analyzes facial and trigeminal nerver function after
      arthroscopic surgery. PATIENTS AND METHODS: Eighty-one consecutive patients (81
      joints) who underwent unilateral temporomandibular joint (TMJ) arthroscopic
      surgery were assessed postoperatively for facial and trigeminal nerve function.
      RESULTS: Twenty-four of 81 patients (29.6%) had some degree of sensory or motor
      nerve dysfunction. Two patients (2.5%) showed signs of facial nerve dysfunction,
      which completely resolved in one patient in 11 weeks, but persisted mildly in the
      other at the 1-year follow-up examination. CONCLUSIONS: Auriculotemporal syndrome
      was not detected in any of the 40 patients tested. However, transient numbness
      over the distribution of the auriculotemporal nerve was present in 19 of 81
      patients (23.4%). This numbness persisted for 3 days to 3 months with a mean
      duration of 14 days. Three of the 81 patients (3.6%) showed signs of inferior
      alveolar and lingual nerve involvement, which returned to normal in 4 to 12 weeks
      in all 3 patients.

PMID- 8530999
TI  - Distraction osteogenesis in maxillofacial surgery using internal devices: review
      of five cases.
AB  - PURPOSE: The purpose of this report is to show the feasibility and potential
      advantages of using internal devices for distraction osteogenesis in the
      management of maxillofacial skeletal deficiencies. PATIENTS AND METHODS:
      Distraction osteogenesis was used to correct a variety of maxillofacial skeletal
      deformities in five patients. One patient underwent bilateral Le Fort III
      advancement aided by distraction, three patients underwent mandibular ramus
      lengthening, and one patient underwent segmental alveolar reconstruction by
      distraction. The devices were activated by either a transcutaneous or
      transmucosal pin. After achievement of the desired skeletal transport, the
      activating pins were disengaged and removed from the distraction device. This
      allowed the distraction device to remain submerged and to stabilize the site of
      the consolidating bone. RESULTS: All patients achieved lengthening of their jaws.
      However, premature consolidation was noted in two patients, and one patient had
      significant relapse. CONCLUSIONS: Development of internal distraction devices is
      important to address the limitations of currently available biphasic systems.
      Potential benefits of internal devices include 1) elimination of skin scarring
      caused by translation of transcutaneous fixation pins, 2) improved patient
      compliance during the fixation or consolidation phase because there is no
      external component, and 3) improved stability of the attachment of the device to
      the bone.

PMID- 8531000
TI  - Age-related changes of the retrodiscal tissues in the temporomandibular joint.
AB  - PURPOSE: This study compares the histologic features of the lateral capsule and
      lateral and central posterior disc attachment of temporomandibular joints (TMJs)
      in young and elderly persons. MATERIAL AND METHODS: Samples were removed from 36
      joints belonging to young persons (mean age, 30 years; age range, 16 to 39 years)
      and 29 joints belonging to elderly persons (mean age, 69 years; age range, 58 to
      78 years). Twelve joints from elderly persons had altered disc position, whereas
      none of the young joints had this condition. Six-micrometer-thick sections were
      stained with hematoxylin-eosin and the Frankel method (for elastic fibers).
      Logistic regression analysis using a likelihood-ratio test was applied for
      comparisons between groups and to avoid the confounding effect of differences in
      disc position and gender. RESULTS: A significantly lower density of fibroblasts
      was observed in elderly persons in all the three areas investigated. In addition,
      elderly persons demonstrated a significantly lower distribution of vascular
      tissue and a significantly higher presence of dense connective tissue in the
      central third of the posterior disc attachment. CONCLUSION: This study shows that
      retrodiscal tissues, which may eventually function as an articular disc during
      altered disc position, are susceptible to age-related connective tissue changes.

PMID- 8531001
TI  - Morphologic and immunohistochemical observation of explanted Proplast-Teflon
      temporomandibular joint interpositional implants.
AB  - PURPOSE: The objective of this study was to investigate the cellular tissue
      response to temporomandibular joint (TMJ) Proplast-Teflon disc material by
      morphologic and immunohistochemical means. PATIENTS AND METHODS: Twelve patients
      who had been subjected to TMJ discectomy combined with insertion of a Proplast
      Teflon interpositional implant (PTIPI) were recalled for removal of the
      alloplastic disc. The time elapsed between the Proplast-Teflon disc implantation
      and its removal varied between 13 and 71 months (mean, 54.6 +/- 5.8 [SEM]) The
      implants and periimplant tissues were examined by light microscopy and
      immunohistochemically using a panel of monoclonal antibodies reactive with
      different subclasses of leukocytes. The sections were immunostained using the
      alkaline phosphatase-antialkaline phosphatase (APAAP) technique. RESULTS:
      Fibrosis and a massive foreign body giant cell reaction were seen inside the
      heavily disrupted alloplastic implants and in the periimplant tissues. CD68
      positive monocyte-derived cells dominated the reactive infiltrate in the implants
      and surrounding tissue. The CD68-positive cells also were partly positive for
      lysozyme. The lymphocytic infiltration contained no B cells. CONCLUSIONS: This
      study of the PTIPI-induced tissue reaction gave no indication of a toxic or an
      immunologic pathogenesis. Mechanical stress seems important in the fragmentation
      of the implant and induction of the foreign body reaction. It is not yet known if
      this fragmentation is the major contributing factor.

PMID- 8531002
TI  - The relationship of the buccal branch of the facial nerve to the parotid duct.
AB  - PURPOSE: This cadaver dissection studied the relationship of the buccal branch of
      the facial nerve to the parotid duct and its relevance to surgical procedures in
      this area. MATERIALS AND METHODS: Ten cadaveric heads (twenty sides) were
      dissected. The superficial tissues were removed, and the buccal branch of the
      facial nerve and the parotid duct were identified. The vertical and horizontal
      relationships were recorded and analyzed. RESULTS: Eighty-five percent of the
      cadavers had a single buccal branch of the facial nerve, whereas 15% had two
      branches. In 75% of cases, the nerve was inferior to the duct as it emerged from
      the parotid gland, whereas in 25% of cases the nerve crossed the duct, usually
      from superior to inferior. CONCLUSION: The buccal branch of the facial nerve has
      a close relationship with the parotid gland for over 2.5 cm after it emerges from
      the parotid gland; it normally lies inferior to the duct. This relationship is of
      importance in performing parotid gland surgery, parotid duct surgery, and some
      facial cosmetic surgery.

PMID- 8531003
TI  - Alveolar cleft bone grafting (Part I): Primary bone grafting.

PMID- 8531004
TI  - Alveolar cleft bone grafting (Part II): Secondary bone grafting.

PMID- 8531005
TI  - Antimicrobial skin preparations for the maxillofacial region.

PMID- 8531006
TI  - Poly(L-lactide) implants for repair of human orbital floor defects: clinical and
      magnetic resonance imaging evaluation of long-term results.
AB  - PURPOSE: The purpose of this study was to evaluate the long-term outcome of
      repair of orbital floor defects in patients with resorbable as-polymerized poly(L
      lactide) (PLLA) implants and to determine whether these patients showed symptoms
      that could be indicative of the presence of a late tissue response. PATIENTS AND
      METHODS: Six patients (four women, two men; mean age, 39 years; range, 18 to 67
      years) treated with PLLA implants for orbital floor fractures were recalled for
      follow-up examination after a period ranging from 3 1/2 to 6 1/2 years. The
      examination consisted of an interview and a physical examination, including an
      ophthalmologic and orthoptic consultation. For evaluation of the orbital tissues,
      coronal spin echo T1- and T2-weighted magnetic resonance images (MRIs) were made
      through both orbits. RESULTS: None of the patients reported any problems in the
      years preceding the follow-up examination that might have indicated
      complications. Clinical examination of the operative sites revealed no
      abnormalities. At ophthalmologic and orthoptic consultation, normal eye function,
      without diplopia or restriction of motility, was found in all patients. The MRIs
      showed no indication of an abnormal or increased soft tissue reaction in the
      orbital region. CONCLUSIONS: Based on the results of this study, it can be
      concluded that PLLA orbital floor implants have the potential for successful use
      in repair of human orbital floor defects.

PMID- 8531007
TI  - Function, biochemistry, and metabolism of the normal synovial membrane of the
      temporomandibular joint: a review of the literature.

PMID- 8531008
TI  - Criteria for consistent and high sensitivity of DNA in situ hybridization on
      paraffin sections: optimal proteolytic enzyme digestion.
AB  - It is technically challenging for the detection of target DNA in low abundancy,
      such as viral DNA sequences in latently infected cells by nonisotopic in situ
      hybridization (ISH). Consistent result is even more difficult to achieve on
      routine paraffin sections. Proteolytic enzyme digestion is most critical for both
      consistency and sensitivity of the technique. We here have investigated the
      effect of enzyme digestion on cell morphology, protein and DNA reduction, and
      hybridization efficiency. The results demonstrated that enzyme digestion improves
      efficiency of ISH through a process involving partial DNA purification on
      sections. There is a clear relationship between proteolytic enzyme digestion,
      morphology changes, and hybridization efficiency. Although detection of DNA
      sequences in abundance can be achieved within a relatively wide range of
      digestion levels, maximum hybridization efficiency was always related to the
      cells, which showed morphology of nuclear swollen, weak homogeneous chromatin
      staining with hematoxylin and loss of visible nuclear membrane. Detection of
      viral DNA in low copy number critically depends on the creation of the
      morphologic changes by enzyme digestion. The morphological changes would
      therefore serve as important criteria for optimal digestion, result
      interpretation, and comparison.

PMID- 8531009
TI  - Comparison of ELISA and HPLC for the determination of desmosine or isodesmosine
      in aortic tissue elastin.
AB  - We developed a rapid and simple method for estimating tissue elastin content by
      measuring desmosine (D) in tissue hydrolysates by competitive ELISA. We compared
      the ELISA previously reported HPLC methods. When D or isodesmosine (ID) in
      hydrolysate of the same elastin preparation were measured by the two different
      methods, a good linear relationship was obtained (r = 0.854 for human aorta or r
      = 0.938 for rabbit aorta, respectively). The ELISA method can detect as little as
      6 pmol/ml and it may be useful in monitoring elastin metabolism in patients with
      various connective tissue diseases.

PMID- 8531010
TI  - Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by
      activated Ki-ras via AP-1 activation in SW1417 colon cancer cells.
AB  - The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix
      metalloproteinase gene family, which is believed to play an important role in
      tumor invasion and metastasis. We have previously found that matrilysin mRNA is
      specifically expressed in colorectal cancers and adenomas and that its message is
      localized in the tumor cells themselves. We examined the effects of activated Ki
      ras oncogene on the expression of matrilysin in colon cancer cells. We showed
      that both mRNA and the enzymatic activity of matrilysin were induced by the
      introduction of activated Ki-ras into SW1417 colon cancer cells. To understand
      the mechanisms regulating this induction, we analyzed alterations of AP-1
      activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase
      assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than
      that in control cells. The gel-shift assay also showed higher levels of AP-1
      binding protein in SW1417 cells expressing activated Ki-ras than those in control
      cells. Our results suggest that activated Ki-ras may play a role in inducing
      expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.

PMID- 8531011
TI  - Development and validation of an automated particle-enhanced nephelometric
      immunoassay method for the measurement of human plasma C1q.
AB  - We have developed a sensitive immunoassay based on latex particle agglutination
      for measuring C1q concentrations in human plasma. In this simple and fast
      particle-enhanced immunoassay, we used carboxylated latex particles (diameter 210
      nm) covalently coated with F(ab')2 fragments of anti-C1q antibodies. These
      particles are incubated with diluted sample (400-fold) for 6 min at room
      temperature, with the resulting agglutination quantified by measuring the change
      of light-scatter produced. The assay has been automated on the Behring
      nephelometer analyzer with a sampling rate of 150 samples/hr. This assay
      generates a standard curve in the range of 24-775 mg/L, showing intraassay and
      interassay precision of < 8% and < 10%, respectively. Dilution linearity was
      validated throughout the dynamic range of the assay. There were no interferences
      from bilirubin, Intralipid, haemoglobin, and rheumatoid factor. Results obtained
      in 45 clinical samples correlated well with those obtained by a commercial radial
      immunodiffusion method (r = 0.936), and with those obtained by the Behring
      immunoprecipitation nephelometric test (r = 0.950). The mean concentration in
      plasma from healthy subjects was 180 mg/L and the reference interval was from 128
      to 237 mg/L. This latex nephelometric procedure is a convenient method and an
      interesting alternative to other immunoassays for routine measurement of human
      C1q.

PMID- 8531013
TI  - Dot-ELISA for the rapid detection of gentamicin in milk.
AB  - A dipstick dot-ELISA for the detection of gentamicin in milk of dairy cattle is
      reported for the first time. The test is based on a sandwich ELISA using high
      affinity monoclonal antibodies to gentamicin. Antibodies were adsorbed to
      nitrocellulose filters, blocked, dried, and stored for several weeks before use.
      The dipstick ELISA detected gentamicin at a concentration of 0.1 microgram/ml and
      produced strongly positive results at 0.2 microgram-0.3 microgram/ml. This ELISA
      is highly specific and no false positives were detected when tested against
      various aminoglycoside analogs including streptomycin, kanamycin, bekanamycin,
      amikacin, neomycin, and tobramycin. Further, the elimination in cow milk of
      gentamicin residues following intramammary administration of the drug was studied
      in two dairy cattle using dot-ELISA. Milk gentamicin levels were detected at post
      injection hours up to 120 hr in each of the two dairy cattle. It therefore,
      appears that gentamicin residues can still be detected in milk after 5 days using
      dot-ELISA. Based on the simplicity of performance and the economical nature of
      the test system, dipstick is recommended as a suitable method for wide scale use
      in field studies and diagnostic laboratories.

PMID- 8531012
TI  - Myelin- and microbe-specific antibodies in Guillain-Barre syndrome.
AB  - We surveyed the frequency of reported infections and target autoantigens in 56
      Guillain Barre syndrome (GBS) patients by detecting antibodies to myelin and
      microbes. Sulfatide (43%), cardiolipin (48%), GD1a (15%), SGPG (11%), and GM3
      (11%) antibodies were the most frequently detected heterogenous autoantibodies. A
      wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps
      specific IgG (66%), adenovirus-specific IgG (52%), varicella-zoster virus
      specific IgG (46%), and S. pneumoniae serotype 7-specific IgG (45%) were the most
      prevalent. Our results indicate that polyclonal expansion of physiologic and
      pathologic antibodies and/or molecular mimicry likely occurs following infection
      and is related to other autoimmune factors in the etiology of GBS. Although no
      single definitive myelin-specific autoantibody was identified, our results
      suggest a unique pattern of reactivity against autoantigens.

PMID- 8531014
TI  - A combined indirect ELISA and immunoblotting for the detection of intrathecal
      herpes simplex virus IgG antibody synthesis in patients with herpes simplex virus
      encephalitis.
AB  - A combined indirect ELISA and immunoblotting assay was used for the detection of
      intrathecal synthesis of IgG antibodies to herpes simplex virus (HSV) in patients
      with HSV encephalitis (HSVE). By using these two assays as well as three markers
      for blood-brain barrier, leakage can be easily excluded. A total of 21 sera and
      24 cerebrospinal fluid (CSF) samples from 11 patients with HSVE were examined.
      For seven patients more than one pair of serum and CSF were available. For one
      patient IgG antibodies began to be detectable in CSF after the sixth day from the
      onset of the disease. In the other 10 patients the intrathecal synthesis of HSV
      IgG antibodies was detected later than the sixth day and reached high optical
      density (OD) values after the 10th day from the onset of disease, at the
      earliest. In contrast, intrathecal HSV antibody synthesis was not found in
      specimens taken from 20 patients with acute meningitis who composed our negative
      control group. The use of a combined indirect ELISA and of an immunoblotting
      assay on a single dilution of serum and CSF for HSV IgG synthesis in the central
      nervous system (CNS) allowed the diagnosis of HSVE after the first week of
      disease.

PMID- 8531015
TI  - (1-->3)-beta-D-glucan in culture fluid of fungi activates factor G, a limulus
      coagulation factor.
AB  - Two well-known polysaccharides, (1-->3)-beta-D-glucan and mannan, are major
      structural components of the fungus cell wall. The G test is a direct method to
      measure (1-->3)-beta-D-glucan using a (1-->3)-beta-D-glucan-sensitive component,
      factor G, fractionated from the limulus lysate. The concentration of (1-->3)-beta
      D-glucan in culture supernatants of Candida albicans increased to 1,390.0 pg/ml
      at 24 hours. The concentration of mannan also increased parallel with fungal
      growth. However, after digestion of supernatants with endo-(1-->3)-beta-D
      glucanase, the reactivity to factor G disappeared, although titers of antimannan
      monoclonal antibody-based latex agglutination were unchanged. Our study
      demonstrated that cell suspensions of both C. albicans and Cryptoccocus
      neoformans activated the limulus factor G, and that not only the conidia form but
      also the filamentous form of Aspergillus fumigatus reacted with factor G. Various
      Candida spp. (C. paraspilosis, C. glabrata, C. tropicalis, C. krusei),
      Saccharomyces cerevisiae, Rhodotorula rubra, Trichosporon beigelii, and A.
      fumigatus released soluble (1-->3)-beta-D-glucan into their culture supernatants,
      but C. neoformans and Cunninghamella bertholletiae showed only a small reaction
      to the G test during their culture. Our results indicate that the G test is a
      good method for serodiagnosis of deep mycosis and also as a screening tool for
      contamination of medical devices, drugs, and experimental materials with (1 -->
      3)-beta-D-glucan.

PMID- 8531016
TI  - Type 2 Gaucher disease without the "complex alleles".

PMID- 8531017
TI  - Detection of antibodies and delayed hypersensitivity with Rotofor preparative IEF
      fractions of Blastomyces dermatitidis yeast phase lysate antigen.
AB  - Blastomyces dermatitidis (dog isolate T-58) yeast phase lysate antigen was
      concentrated and separated by Rotofor preparative isoelectric focusing cell (Bio
      Rad). The pH values of the fractions were determined and equilibrated to pH 7.2
      and then analysed by enzyme-linked immunosorbent assay using horseradish
      peroxidase enzyme system against serum specimens from dogs with blastomycosis,
      histoplasmosis, aspergillosis, and coccidioidomycosis. The results showed a peak
      absorbance at pH 3.89-4.31 (fractions 4 and 5) with the blastomycosis serum
      specimens. This was a single sharp peak while the rest of the fractions were
      lower. In contrast the sera from dogs with histoplasmosis showed a peak
      absorbance at pH 5.54-5.97 (fractions 9 and 10), while the other mycoses showed
      patterns that did not resemble the blastomycosis or histoplasmosis specimens.
      Serum specimens from dogs with blastomycosis being treated with itraconazole were
      also assayed (pre-treatment and 1, 2, 3, and 12 months post-treatment sera). The
      characteristic peak for blastomycosis was observed and a decrease in the peak was
      seen as the treatment progressed. Fractions 3-12 were also used to detect delayed
      dermal hypersensitivity in hyperimmunized hairless guinea-pigs. Fraction 5 (pH
      4.31) elicited the optimal response in B. dermatitidis-immunized animals, while
      no cross-reactivity was observed in guinea-pigs sensitized with Histoplasma
      capsulatum killed cells.

PMID- 8531018
TI  - The 5S rRNA and the rRNA intergenic spacer of the two varieties of Cryptococcus
      neoformans.
AB  - The intergenic spacers (IGS) separating the 23S-like and 16S-like rDNAs of the
      two varieties of the human pathogenic fungus Cryptococcus neoformans were
      amplified, cloned and sequenced. The C. neoformans var. neoformans IGS was 2421
      nt with 5S rRNA at positions 1228-1345 3' of the 23S-like rRNA. The C. neoformans
      var. gattii IGS was 2480 nt with 5S rRNA at positions 1268-1385 3' of the 23S
      like rRNA. For both varieties the 5S rDNA genes were in the same orientation as
      the 16S-5.8-23S genes and encode a 118 nt molecule of identical sequence.
      Phylogenetic comparison of C. neoformans 5S rDNA with that of other fungi placed
      this fungus in close relationship with other basidiomycetes including Tremella
      mesenterica, Bullera alba, and Cryptococcus laurentii. A secondary structure
      model for the deduced 5S rRNA was constructed by comparative sequence analysis.
      Polymerase chain reaction-amplified IGS of 12 C. neoformans var. neoformans
      strains revealed extensive size variation ranging from 100 to 300 nt. Size
      variation between strains in the length of the IGS may be useful for
      distinguishing strains. Structurally, the IGS were characterized by the presence
      of occasional short direct GC-rich 19-nt repeats. Overall IGS sequence identity
      between the C. neoformans varieties was only 78.5%, in sharp contrast to the
      identical or nearly identical sequences for the rDNA genes, and suggests rapid
      evolution for IGS sequences.

PMID- 8531019
TI  - Expression and isoforms of gp43 in different strains of Paracoccidioides
      brasiliensis.
AB  - Individual exoantigens from 13 Paracoccidioides brasiliensis isolates were
      obtained and tested against a panel of 50 sera from patients with
      paracoccidioidomycosis by immunodiffusion test. The index of positivity varied
      from 20 to 100% according to the isolate. When these exoantigens were analysed by
      SDS-PAGE, eight presented high amounts of the glycoprotein gp43, two presented
      small amounts and in three there was no detectable gp43. The eight isolates
      presenting high amounts of gp43 were submitted to isoelectric focusing, blotted
      to nitrocellulose membranes, and revealed by monoclonal and polyclonal anti-gp43
      antibodies. Four gp43 isoform profiles were obtained: profile A presenting pIs of
      6.0, 6.2, 6.6 and 7.0, profile B presenting pIs of 6.4, 6.8 and 7.2, profile C
      presenting pI > 8.5 and profile D, presenting pIs of 5.8, 6.2 and 6.6. In each
      pattern observed, a major band with a distinct pI was detected. Despite this
      variation, our results strongly suggest an epitopic conservation among all
      isoforms analysed, since all of them were recognized by anti-gp43 monoclonal
      antibodies.

PMID- 8531020
TI  - Activity of terbinafine on Trichophyton mentagrophytes in a human living skin
      equivalent model.
AB  - Germination of arthroconidia of Trichophyton mentagrophytes in the presence of
      the allylamine antifungal terbinafine was assessed utilizing a human living skin
      equivalent model. Arthroconidia were inoculated onto the skin-equivalent
      previously exposed to low concentrations of terbinafine (0.01-1.0 mg l-1) and
      then incubated at 28 degrees C for 7 days. An assessment of fungal growth
      inhibition was made by light and scanning electron microscopy. In the absence of
      terbinafine, adherence, germination and hyphal extension were observed.
      Penetration of the model was seen, with hyphae present in the dermal component.
      In the presence of terbinafine, inhibition of fungal growth was apparent and the
      drug was seen to act as a barrier against fungal invasion of the dermis. The data
      indicate that the living skin equivalent model is a promising in vitro system for
      evaluating new antifungal agents.

PMID- 8531021
TI  - Sex hormone effects on Phialophora verrucosa in vitro and characterization of
      progesterone receptors.
AB  - To determine the effects of sex steroid hormones on the growth of an aetiologic
      agent of chromoblastomycosis, we studied the dematiaceous fungus Phialophora
      verrucosa. The in vitro growth of this species on culture media containing either
      progesterone, testosterone or oestradiol at various concentrations was assessed.
      Both progesterone and testosterone inhibited the growth of P. verrucosa, whereas
      oestradiol did not. In other experiments, fungal cytosolic fractions were
      obtained and steroid binding assays were performed. These studies showed that the
      presence of progesterone receptors possessed two binding sites as determined by
      Scatchard analysis, one of which has a high affinity to progesterone (Kd = 6.02 x
      10(-8) M) with total binding sites of 120 fmol micrograms-1 protein. These
      findings suggest that the growth of P. verrucosa is regulated by steroid hormones
      and that the effect of progesterone could be mediated through fungal
      intracellular progesterone receptors.

PMID- 8531022
TI  - Random amplified polymorphic DNA for strain delineation within Candida
      tropicalis.
AB  - Candida tropicalis DNA was used as a template in a polymerase chain reaction
      (PCR) utilizing a 10-mer primer to generate random amplified polymorphic DNA
      (RAPD). RAPD patterns associated with 25 primers were obtained for six
      epidemiologically-unrelated isolates, then a subset of six primers were selected
      to screen a panel of 18 isolates of C. tropicalis and six isolates of Candida
      paratropicalis, a species that resembles C. tropicalis but has a sucrose-negative
      phenotype. The panel, which included nine epidemiologically-related isolates from
      an outbreak of sternal wound infections, was typed without knowledge of each
      isolate's origin. The RAPD profiles of the epidemiologically-related isolates
      were identical to very similar; in contrast, the profiles of most unrelated
      isolates showed more dissimilarity. While RAPD profiles of C. albicans and
      Candida parapsilosis differed substantially from those of C. tropicalis, the
      profiles obtained for C. paratropicalis were consistent with it being a variant
      of C. tropicalis.

PMID- 8531023
TI  - Glycolipids from Paracoccidioides brasiliensis. Isolation of a galactofuranose
      containing glycolipid reactive with sera of patients with paracoccidioidomycosis.
AB  - In the present study, we describe the isolation of glycolipids from yeast and
      mycelium forms of Paracoccidioides brasiliensis. Both forms contains
      glucosylceramide as the only neutral glycosphingolipid and two acidic glycolipids
      termed band 1 and band 2. Band 1 was found to be reactive with 100% of sera of
      patients with paracoccidioidomycosis tested. Structural analysis of band 1
      revealed that it is composed of mannose and galactose in molar ratios of 2:1, and
      a trace amount of glucose. Furthermore, this paper presents evidence that the
      galactose unit of band 1 is in the furanose configuration. Finally, it was found
      that reactivity of paracoccidioidomycosis sera with band 1 glycolipid can be
      attributed mainly to antibodies directed to galactofuranosyl residue present in
      this glycoconjugate.

PMID- 8531024
TI  - Superoxide dismutase of Cryptococcus neoformans: purification and
      characterization.
AB  - We have purified to homogeneity a putative superoxide dismutase of 19.5 kDa from
      the pathogenic yeast Cryptococcus neoformans by homogenization, isoelectric
      focusing and gel filtration. The N-terminal amino acid sequence of this protein
      indicates a significant sequence homology with known manganese-containing
      superoxide dismutases (Mn-SODs) from various organisms. In addition, the presence
      of superoxide dismutase activity was confirmed using specific substrate gels
      which detect this enzyme when nitro-tetrazolium blue reduction is prevented by
      the photochemical source of superoxide, in the presence of riboflavin when
      exposed to light. Superoxide dismutase activity was also assayed using cytochrome
      c. The molecular weight of the native enzyme (on non-denaturing gels) is 80 kDa.
      The optimum pH for the enzyme is 7.5 and its pi = 6.6. The enzyme was inhibited
      by sodium dodecyl sulphate, sodium azide, o-phenanthroline, and EDTA, in
      descending order.

PMID- 8531025
TI  - The actin gene from Cryptococcus neoformans: structure and phylogenetic analysis.
AB  - Using heterologous probing of a genomic library, we have cloned and sequenced the
      actin gene from the pathogenic yeast Cryptococcus neoformans. The actin gene is
      1371 bp in length, and exists as a single copy, as is the case for all fungi
      studied to date. The locations of the introns in the C. neoformans actin gene are
      unique among all other known actin genes, and the deduced coding sequence results
      in a 375 amino acid chain with very high homology to other actins. A phylogenetic
      tree comprising 31 actin-coding sequences from a wide variety of organisms shows
      that the C. neoformans actin gene is grouped on a distinct branch together with
      all other known fungal actin sequences. The availability of the C. neoformans
      actin gene will aid future phylogenetic and molecular studies of this important
      human pathogen.

PMID- 8531026
TI  - Central venous catheter infection with Rhodotorula minuta in a patient with AIDS
      taking suppressive doses of fluconazole.
AB  - A case of Rhodotorula minuta central venous catheter infection with fungaemia is
      described in a patient with advanced acquired immunodeficiency syndrome (AIDS),
      HIV nephropathy, end-stage renal disease requiring haemodialysis, and a permanent
      Quinton catheter in place for 6 months. At the time of fungaemia, the patient was
      taking 100 mg fluconazole per os daily for a previous episode of Candida
      oesophagitis. R. minuta central venous catheter infection with fungaemia was
      successfully treated with 455 mg total dose amphotericin B (0.6 mg kg-1 day-1)
      over 25 days without removal of the catheter. In vitro antifungal susceptibility
      testing for R. minuta revealed a minimum inhibitory concentration to fluconazole
      of > 100 micrograms ml-1 and to amphotericin B of 1.2 microgram ml-1. Clinically
      evident fungaemia, even with an unusual organism such as R. minuta, may occur in
      patients with intravenous catheters, and while the immunosuppressed patient is
      receiving azole therapy.

PMID- 8531027
TI  - Efficiency of the flotation method in the isolation of Penicillium marneffei from
      seeded soil.
AB  - The efficiency of a modified flotation method for the isolation of Penicillium
      marneffei from soils has been evaluated. About 80% was recovered from sterilized
      soil freshly seeded with P. marneffei (100 conidia/1.5 g soil). When seeded non
      sterile soil was used (at least 100 seeded conidia/1.5 g soil), P. marneffei
      could be effectively recovered by employing a combination of the flotation method
      and the mouse inoculation method.

PMID- 8531028
TI  - pH-dependent denaturation of extracellular aspartic proteinases from Candida
      species.
AB  - The yeasts Candida albicans. Candida tropicalis, and Candida parapsilosis secrete
      aspartic proteinases which may enhance virulence. Profiles of pH-dependent
      irreversible denaturation of such enzymes were determined at 37 degrees C. C.
      albicans proteinases from both serotypes A and B maintained 50% of their activity
      near pH 7.25. Proteinases from C. parapsilosis and C. tropicalis lost 50% of
      their activity at pH 6.75 and pH 6.15, respectively. This suggests that in the
      infected host only proteinases of C. albicans maintain a native state for any
      length of time.

PMID- 8531029
TI  - Purification and characterization of an extracellular aspartic proteinase from
      Aspergillus fumigatus.

PMID- 8531030
TI  - Spasmus nutans: what to do?

PMID- 8531031
TI  - On infantile esotropia with nystagmus in abduction.
AB  - Infantile esotropia with nystagmus in abduction is characterized by early onset,
      jerk nystagmus in abduction, and dissociated vertical deviation, among other
      features. Electro-oculographic tracings present easily recognizable patterns both
      in saccadic and pursuit movements. Visual evoked responses are asymmetric in most
      cases and optokinetic nystagmus is invariably asymmetric. Visual cortex
      maldevelopment seems to play a major pathogenic role. Recent findings in
      myelomeningocele and in patients with posterior fossa tumors suggest that
      pathological alterations in this area may tend to induce similar anomalies in
      electro-oculographic and optokinetic nystagmus recordings. Posterior fossa damage
      or impairment is therefore suspected to be a possible causative factor in the
      development of infantile esotropia with nystagmus in abduction.

PMID- 8531032
TI  - Photoscreening for amblyogenic factors.
AB  - BACKGROUND: The Medical Technology Inc (MTI) Photoscreener is a new eccentric
      photoscreener that is being marketed as a device for the detection of amblyogenic
      factors in preverbal children. The purpose of this study was to evaluate the
      accuracy of the MTI Photoscreener in the target population of young, healthy
      children. METHODS: One thousand and three healthy children between the age of 6
      months and 59 months were photoscreened with the MTI Photoscreener. Nine hundred
      and forty nine children were included in the study and their results were
      compared with a complete ophthalmologic examination with cycloplegia. RESULTS:
      The sensitivity of the MTI Photoscreener was determined to be 81.8% with a
      specificity of 90.6%. The overall agreement rate was 88.8%. The positive and
      negative predictive values were 68.9% and 95.2%, respectively. All cases of
      strabismus and media opacities were detected. CONCLUSION: The MTI Photoscreener
      is an accurate and reliable device designed to detect amblyogenic factors in
      young children. The camera offers promise as a useful mass-screening tool.

PMID- 8531033
TI  - Prevalence of intracranial lesions in children initially diagnosed with
      disconjugate nystagmus (spasmus nutans)
AB  - A small number of children who develop disconjugate nystagmus, torticollis, and
      head titubation (spasmus nutans) have been found to have optic chiasm or third
      ventricle gliomas. However, the prevalence of glioma or other developmental
      abnormalities in this disorder is unknown because no large series of spasmus
      nutans cases has previously been reported. A reviewer of the records of 67
      consecutive children initially diagnosed with spasmus nutans and followed for an
      average of 3.3 years at the St Louis Children's Hospital revealed the following:
      61% had a history of prematurity, developmental delay, or other systemic
      abnormality; strabismus, most commonly infantile esotropia, developed in 55%; 43%
      had neuroimaging studies; and 0% had evidence of a glioma or showed signs of
      tumor on follow-up examinations. From this consecutive patient series, we
      estimate the prevalence of tumor in spasmus nutans to be less than 1.4%. Without
      other evidence of an intracranial mass lesion, neuroimaging of infants initially
      diagnosed with spasmus nutans may not be immediately warranted.

PMID- 8531034
TI  - Can non-ophthalmologists screen for retinopathy of prematurity?
AB  - BACKGROUND: Dilation and tortuosity of the posterior pole vessels ("plus
      disease") is a poor prognostic sign and may indicate the presence of threshold or
      pre-threshold retinopathy of prematurity (ROP). Because stage 3 ROP appears
      rarely in the absence of posterior pole vascular abnormalities, we prospectively
      evaluated the ability of non-ophthalmologists (4th-year medical students,
      pediatric residents, and nurse practitioners) to identify abnormalities in the
      retinal blood vessels of infants undergoing examinations for ROP. METHODS: Fifty
      infants weighting less than 1600 g at birth were examined between 32 and 40 weeks
      after conception. Prior to ophthalmological examination, non-ophthalmologist
      examiners graded posterior pole vessels as normal or abnormal based on
      ophthalmoscopic appearance. One hundred twenty-one ocular examinations were
      performed using the teaching mirror of the indirect ophthalmoscope, 179 using the
      direct ophthalmoscope. The indirect ophthalmoscopy was performed simultaneously
      by an ophthalmologist who evaluated the posterior pole vessels for abnormalities
      prior to conducting a peripheral fundus examination on either eye. RESULTS:
      Testing sensitivity for the non-ophthalmologist examiners using direct and
      indirect ophthalmoscopy was 96% and 92%, respectively. Combining the results from
      direct and indirect ophthalmoscopy, the Clopper-Pearson 95% sensitivity
      confidence interval for identifying abnormal arterioles and venules was 82% to
      99%, with a point estimate of 95%. CONCLUSION: These data suggest that non
      ophthalmologist examiners can detect posterior pole vascular abnormalities in
      premature infants. If properly trained, they could possibly play a role in
      screening or follow-up examinations for ROP.

PMID- 8531035
TI  - The treatment of congenital nystagmus with Botox.
AB  - Clostridium botulinum A exotoxin (Botox) is the most potent toxin known to man.
      It produces a reversible paralysis of cholinergically innervated muscle, an
      effect useful in the management of non-accommodative strabismus and various
      disabling focal dystonias. In the present study, botulinum toxin (Botox) was used
      to treat congenital nystagmus, injecting the toxin into multiple horizontal
      rectus muscles at the same treatment session. Three of four patients achieved a
      significant enough change in acuity to receive daytime-restricted driver's
      licenses. No treatment was complicated by retrobulbar hemorrhage, ocular
      perforation, or ptosis. Two patients are continuing the Botox treatments every 3
      to 4 months.

PMID- 8531036
TI  - Strabismus associated with meningomyelocele.
AB  - INTRODUCTION: Strabismus occurs frequently in patients with spina bifida or
      meningomyelocele. PATIENTS AND METHODS: I performed 1544 eye examinations in 298
      patients with spina bifida over a period of 15 years. The patient records were
      retrospectively reviewed for visual acuity, binocular function, and strabismus.
      Select patients with A-pattern strabismus were recalled for neuroimaging.
      RESULTS: Visual acuity was correctable to 20/40 in 85% of the patients. One
      hundred and eighty-three patients (61%) had strabismus at some time over the
      study period. Sixty-three percent had an esodeviation; 37% an exodeviation. A
      pattern strabismus was more common in patients with exotropia (39%) than in those
      with esotropia (27%). Defects on neuroimaging in the region of the vertical gaze
      pathways in the brain stem were correlated with A-pattern strabismus. CONCLUSION:
      With increased longevity of the patient with spina bifida, quality-of-life issues
      become increasingly important. Amblyopia, strabismus, and other acquired defects
      in the visual system related to hydrocephalus should be closely monitored and
      treated when indicated.

PMID- 8531037
TI  - Ultrastrucure of the superior oblique tendon.
AB  - Individual collagen fibers in the superior oblique tendon of patients with
      superior oblique palsy studied at 60,000x with transmission electron microscopy
      are fewer in number and larger in diameter when compared to normal fibers. The
      relationship of these changes to function and to gross morphologic changes are
      not clear.

PMID- 8531038
TI  - Treatment of retinoblastoma with indirect ophthalmoscope laser photocoagulation.
AB  - INTRODUCTION: The indirect ophthalmoscope laser photocoagulation delivery system
      is relatively new and is potentially applicable for treating selected small
      retinoblastomas. There has been very little reported on the results achieved with
      this laser delivery system in the treatment of retinoblastoma. METHODS: We
      reviewed all patients with retinoblastoma managed by indirect ophthalmoscope
      laser photocoagulation on the Ocular Oncology Service between July 1, 1991 and
      July 1, 1994. The individual tumor size, location, and proximity to the optic
      disc and foveola, as well as the laser power, duration, and number of sessions
      ,were recorded. We assessed the tumor response to treatment and the visual
      outcome of the patients. RESULTS: There were 30 retinoblastomas in 20 eyes of 18
      patients managed with indirect ophthalmoscope laser photocoagulation over the 3
      year period. The mean tumor base was 2.1 mm (range: 1 mm to 8 mm); the mean tumor
      thickness, 1.2 mm (range: 0 mm to 3 mm). The tumor margin was a mean of 6.5 mm
      (range: 0 mm to 19 mm) from the foveola, and 7.7 mm (range: 0 mm to 22 mm) to the
      optic disc. In general, it required a power of approximately 350 mW and a
      continuous duration lasting 1 to 4 seconds to obtain satisfactory obliteration of
      feeding blood vessels. The tumor responded in one to three sessions (mean: 1.9
      sessions per tumor). Complete regression occurred in 21 tumors (70%) and local
      recurrence in nine (30%). The recurrent tumors were successfully treated with
      plaque radiotherapy in seven cases and cryotherapy in two cases. The central
      vision was minimally distorted due to foveal traction from the laser treatment in
      three cases. CONCLUSION: Indirect ophthalmoscope laser photocoagulation is an
      effective conservative method to manage selected small retinoblastomas. Tumors
      treated by this technique should be followed closely due to the moderate risk for
      local recurrence.

PMID- 8531039
TI  - Neuroanatomic abnormalities of primary visual cortex in macaque monkeys with
      infantile esotropia: preliminary results.
AB  - To explore the structural basis for visuomotor deficits in infantile esotropia,
      we examined binocular connections and metabolic activity in the primary visual
      cortex of two strabismic macaque monkeys. The animals were documented to have
      onset of natural esotropia in early infancy. Behavioral testing showed that the
      animals had normal visual acuity in both eyes and the ocular motor deficits that
      characterize strabismus with onset in infancy. The neuronal tracer substance
      biotinylated-dextran-amine was injected into ocular dominance columns (ODC) in
      area V-1 (striate cortex), revealing a paucity of binocular connections between
      right-eye and left-eye ODCs. The metabolic label cytochrome-oxidase was used to
      stain neighboring right-eye and left-eye ODCs, revealing inequalities in
      metabolic activity compatible with interocular suppression. These results show
      that infantile esotropes have abnormalities of visual cortex structure that
      correlate with abnormalities in binocular behaviors.

PMID- 8531040
TI  - Blow-out fracture or subperiosteal hematoma?

PMID- 8531041
TI  - Corneal keloid from unusual penetrating trauma.

PMID- 8531042
TI  - Ophthalmic abnormalities in molybdenum cofactor deficiency and isolated sulfite
      oxidase deficiency.

PMID- 8531043
TI  - Red/green dichotic image separation.

PMID- 8531044
TI  - Self-evaluation processes: motives, information use, and self-esteem.
AB  - At least three motives guide self-evaluation: accuracy, self-enhancement, and
      self-improvement. To satisfy these motives, self-evaluation may utilize different
      information sources. Self-esteem may also moderate self-evaluation strategies.
      Participants evaluated the frequency and usefulness of eight types of information
      for meeting the three motives in two life domains: academics and social life.
      Personal standards information was reported to be used more frequently than
      objective or social comparison information and also perceived as most useful for
      meeting all three motives. Individuals low in self-esteem reported using more
      social comparison information than those high in self-esteem, especially upward
      social comparison information. Individuals with high self-esteem reported using
      personal standards information more often than they used social comparison
      information, while individuals with low self-esteem relied equally often on these
      two types of information. Discussion focuses on the role social comparison
      information may have for those with unstable self-concepts.

PMID- 8531045
TI  - Personality and parenting: exploring the mediating role of transient mood and
      daily hassles.
AB  - In order to explore the role that transient mood and daily hassles might play in
      mediating the impact of enduring personality on parenting, naturalistic home
      observations of mothering and fathering were conducted when firstborn sons were
      15 and 21 months of age. Observationally based, behavioral ratings of mothering
      and fathering were related to three self-report personality scales
      (Agreeableness, Neuroticism, Extraversion), administered to parents when their
      children were 10 months of age, and to self-reports of transient mood (positive
      and negative) and daily hassles obtained prior to each observation of family
      interaction. Results indicated that (a) mothering was more consistently predicted
      by personality and mood/hassles than fathering; (b) Extraversion played a larger
      role in predicting fathering than mothering, with the reverse being true of
      Agreeableness; (c) Neuroticism was the most consistent predictor of men's and
      women's parenting; and (d) there was little support for affect-specific linkages
      between personality, mood/hassles, and parenting. Finally, some evidence of
      mediation by transient mood and daily hassles emerged, more consistently for
      mothers than fathers, though more strongly for fathers than mothers. These
      results are discussed in terms of the primacy of the role of parenting for men
      and women.

PMID- 8531046
TI  - Wishes, motives, goals, and personal memories: relations of measures of human
      motivation.
AB  - The purpose of this study was to compare measures of explicit and implicit
      motives. One hundred and one participants completed six measures of motivation,
      including Thematic Apperceptive stories, autobiographical memories, three wishes,
      personal striving lists, the Personality Research Form, and self-ratings.
      Stories, memories, wishes, and strivings were content-analyzed using Winter's
      (1989) system. Although overall correlations did emerge among explicit measures
      within the same motive, there were numerous correlations among methodologically
      similar measures of different motives. In general, explicit measures did not
      correlate with thematic measures of the same motives. Although correlations among
      measures were similar for men and women, explicit measures of power converged
      with thematic measures of power only for men. Exploratory factor analysis
      identified three factors: explicit achievement, explicit affiliation, and power.
      Implicit achievement motivation loaded negatively on the affiliation factor.
      Implications for research on implicit and self-attributed motivation are
      discussed.

PMID- 8531047
TI  - The orphan receptor family RZR/ROR, melatonin and 5-lipoxygenase: an unexpected
      relationship.
AB  - The orphan receptors RZR alpha, RZR beta, ROR alpha 1, RZR alpha 2, ROR alpha 3,
      and ROR gamma form a subfamily within the superfamily of nuclear hormone
      receptors. Recently, experimental evidence that the pineal gland hormone
      melatonin is the natural ligand for these nuclear receptors has come to light.
      This discovery is rather surprising, given that most people in the field believed
      melatonin acts exclusively through membrane receptors. However, these new
      findings establish a nuclear signalling pathway for melatonin, i.e., direct
      ligand-induced control of target gene transcription, which most probably mediates
      part of the physiological functions of the hormone. Interestingly, the very
      recently identified first RZR/melatonin responding gene, 5-lipoxygenase, is not
      expressed in the brain and is not involved in circadian rhythmicity, but rather
      acts in the periphery, mainly in myeloid cells, as one of the key enzymes of
      allergic and inflammatory reactions. Thus, nuclear melatonin signalling opens up
      a new perspective in understanding the actions of the pineal gland hormone.

PMID- 8531048
TI  - Pineal gene expression: dawn in a dark matter.
AB  - The mammalian pineal gland serves as a neuroendocrine interface to convert
      environmental lighting conditions into a humoral message, the nocturnally
      elevated synthesis of melatonin. Regulation and fine tuning of the circadian
      melatonin production in response to external cues requires complex interactions
      of transsynaptic signalling. These requirements are fulfilled by a high degree of
      plasticity on all levels between receptor activation and cellular response. Many
      receptors on pinealocytic membranes and enzymes involved in melatonin synthesis
      are linked to the second messenger cAMP. Crosstalk between second and third
      messengers converges in the pineal gland--as in other tissues--eventually on a
      modulated activity of transcription factors. Of fundamental importance for genes
      involved in the transsynaptic signalling to create a circadian profile in
      melatonin synthesis is the cAMP-inducible promoter element, the CRE (cAMP
      responsive element). Indeed, the CRE is shared by many pineal genes that are of
      physiological importance. Recently, the deciphering of molecular determinants
      regulating expression of cAMP-inducible genes in the mammalian pineal gland, like
      NAT, c-jun, or the beta-adrenergic receptor suggests a modulation in their
      transcription by a dual regulatory mechanism: posttranslational activation of the
      early third messenger CREB (cAMP responsive element binding protein) stimulates,
      cis-acting cAMP-induced transcriptional upregulation of the late third messenger
      ICER (inducible cAMP early repressor) inhibits genes with a CRE.

PMID- 8531049
TI  - The long-term effect of pinealectomy on the crypts of the rat gastrointestinal
      tract.
AB  - Previously it has been found that rat small bowel crypt cell hyperplasia occurred
      several weeks after pinealectomy. To determine if this effect was longer-lasting
      (because of the possible role of the pineal in bowel malignancy) the crypt cell
      proliferation rate was determined in rat small bowel and colon 6 months after
      pinealectomy, using a stathmokinetic technique. Although the hyperproliferative
      effect of pinealectomy was well maintained in the small bowel crypts after 6
      months, the hyperproliferative effect in the colonic crypts was much less marked.
      There is no obvious explanation for these findings, although it is possible that
      regional differences in levels of gut neuropeptides or melatonin are involved.
      The mechanism of the effect of pinealectomy on the crypts remains unexplained--in
      particular, why the effect is so prolonged.

PMID- 8531050
TI  - Effects of the chemical denervation on the glial cells of the rat pineal gland:
      an immunocytochemical study during postnatal development.
AB  - We have studied the postnatal evolution of the glial cells in the rat pineal
      gland after its chemical pre- and perinatal denervation, by the assessment of the
      immunocytochemical expression of three antigens characteristic of glial cells
      i.e., vimentin (VIM), glial fibrillary acidic protein (GFAP), and S-100 protein.
      The neurotoxic agents we applied consisted of 6-hydroxydopamine (6-OHDA)
      administered during the first 5 postnatal days, and N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4) injected to pregnant rats in the 15th gestational day.
      VIM immunoreactivity was detected in pineal glial cells from the first postnatal
      day, both in denervated and control groups. However, in denervated glands, the
      maturation process of the glial cells is considerably accelerated, since they
      appear completely detached of the connective tissue septa at day 15. From day 30,
      the number of VIM-positive structures progressively increases until adulthood,
      when a large number of immunoreactive cell processes produces a reticular
      appearance to the denervated pineal gland. The first GFAP and S-100 protein
      immunoreactive cells were observed earlier in denervated animals (5th postnatal
      day for S-100 protein, and 10th postnatal day for GFAP) compared with controls.
      In the experimentally denervated groups, the population of positive cells, as
      well as their size and the number of their cell processes, is considerably higher
      and progressively increased. They were always characteristically located in the
      proximal half of the gland. From day 45, this region of the gland shows a notable
      amount of hypertrophic positive cells with thick processes, showing a gliotic
      aspect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531051
TI  - Distribution and characterization of the melatonin receptors in the hypothalamus
      and pituitary gland of three domestic ungulates.
AB  - With some exceptions, in most of the mammals the pituitary pars tuberalis and the
      hypothalamic suprachiasmatic nuclei are reportedly the main targets for the
      pineal hormone melatonin. However, it is not known if the conspicuous diversity
      in the distribution pattern of melatonin binding sites in these areas depicts
      differences in reproductive behavior observed in the seasonally breeding species
      in the temperate zones. We explored the distribution and the characteristics of
      melatonin binding sites in the hypothalamus and pituitary of three species
      (bovine, horse, and donkey) different in terms of seasonal reproductive
      competence. The topographical localization, investigated by in vitro
      autoradiography, revealed 2-[125I]iodomelatonin binding sites only in the
      pituitary gland in all three species, primarily in the pars tuberalis (PT), but
      also in the pars distalis (PD) and pars intermedia (PI). Kinetic, inhibition, and
      saturation studies, performed by means of in vitro binding, revealed presence of
      a single class high affinity binding sites. The Kd values, melatonin, and 2
      iodomelatonin Ki values were in the low picomolar range. Coincubation with GTP
      gamma S inhibited 2-[125I]iodomelatonin binding, demonstrating that these
      putative receptors are linked to a G protein in their signal-transduction
      pathway. The hypothalamus was devoid of specific binding. In conclusion, the
      results suggest that in these species, the hypophysis may be a principal target
      for the melatonin action on the reproductive system.

PMID- 8531052
TI  - N-acetyltransferase, hydroxyindole-O-methyltransferase and melatonin in the optic
      lobes of the giant tiger shrimp Penaeus monodon.
AB  - The activities of the enzymes N-acetyltransferase (NAT) and hydroxyindole-O
      methyltransferase (HIOMT) and the hormone melatonin were studied in the optic
      lobe of the subadult giant tiger shrimp Penaeus monodon. Compared with the level
      in other species, a relatively high level of NAT activity that was temperature-
      and pH-dependent were observed. The NAT enzyme had a relatively high maximum
      velocity (Vmax, 100 pmol/hr/micrograms protein) and low Michaelis constant (Km,
      22 microM), when tryptamine is used as substrate. In contrast to the high level
      of NAT activity, HIOMT activity and melatonin levels were low in the optic lobe
      of the giant tiger shrimp. Sex differences in the levels of NAT activity and
      melatonin, which are observed in a freshwater species Macrobrachium rosenbergii,
      were not noticeable in the saltwater species P. monodon, at least not when they
      were in their subadult stage.

PMID- 8531053
TI  - Melatonin protects neurons from singlet oxygen-induced apoptosis.
AB  - Singlet oxygen (O2[1 delta g]) is a very reactive molecule that can be produced
      by living cells and may contribute to cytotoxicity. The pineal hormone melatonin
      has been reported to possess potent antioxidant activity, and to be capable of
      scavenging O2(1 delta g). We investigated whether melatonin might reduce the
      neurotoxic action of O2(1 delta g). The cytotoxic effect of singlet oxygen was
      studied in primary cultures of cerebellar granule neurons pretreated with a
      photosensitive dye, rose bengal, and exposed to light--a procedure that generates
      O2(1 delta g). We found that this procedure triggers neuronal death, which is
      preceded by mitochondrial impairment (assayed by the rate of the reduction of
      MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, into
      formazan), and by DNA fragmentation--a marker of apoptosis. DNA fragmentation was
      determined in situ by terminal deoxynucleotidyl transferase assay; cell death was
      assayed with 0.4% trypan blue solution--viable cells with an intact membrane are
      not permeable to trypan blue; dead cells are, and thus, they are stained blue.
      Neuroprotection was obtained with the pineal hormone melatonin. In a cell-free
      system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the
      rose bengal-induced injury. The results suggest that melatonin might counteract
      the cytotoxic action of singlet oxygen. Further studies are needed to clarify the
      exact role singlet oxygen and melatonin might play in neurodegenerative diseases.

PMID- 8531054
TI  - Variability in automatic activation as an unobtrusive measure of racial
      attitudes: a bona fide pipeline?
AB  - The research examines an unobtrusive measure of racial attitudes based on the
      evaluations that are automatically activated from memory on the presentation of
      Black versus White faces. Study 1, which concerned the technique's validity,
      obtained different attitude estimates for Black and White participants and also
      revealed that the variability among White participants was predictive of other
      race-related judgments and behavior. Study 2 concerned the lack of correspondence
      between the unobtrusive estimates and Modern Racism Scale (MRS) scores. The
      reactivity of the MRS was demonstrated in Study 3. Study 4 observed an
      interaction between the unobtrusive estimates and an individual difference in
      motivation to control prejudiced reactions when predicting MRS scores. The
      theoretical implications of the findings for consideration of automatic and
      controlled components of racial prejudice are discussed, as is the status of the
      MRS.

PMID- 8531055
TI  - Sensitivity to varying gains and losses: the role of self-discrepancies and event
      framing.
AB  - Three studies psychophysically measured people's discrimination among different
      sizes of monetary net gains or net losses. Participants imagined either gains or
      nonlosses (i.e., net gains) or losses or nongains (i.e., net losses).
      Participants discriminated more when the identical event was framed as the
      presence (gains and losses) versus the absence (nonlosses and nongains) of an
      outcome, presumably because the latter is harder to represent. Discrimination was
      enhanced when the motivational features of the imagined event were either both
      the same as or both different from a person's self-discrepancy. Discrimination
      was reduced when only one of the motivational features was different. A model of
      excitations, inhibitions, and disinhibitions between mental representation is
      suggested to account for these findings.

PMID- 8531056
TI  - Female judgment of male attractiveness and desirability for relationships: role
      of waist-to-hip ratio and financial status.
AB  - Two studies were conducted to examine the role of male body shape (as defined by
      waist-to-hip ratio [WHR]) in female mate choice. In Study 1, college-age women
      judged normal-weight male figures with WHR in the typical male range as most
      attractive, healthy, and possessing many positive personal qualities. In Study 2,
      18-69-year-old women rated normal-weight male figures with differing WHRs and
      purported income for casual (having coffee) to most-committed (marriage)
      relationships. All women, regardless of their age, education level, or family
      income, rated figures with WHRs in the typical male range and higher financial
      status more favorably. These findings are explained within an evolutionary mate
      selection context.

PMID- 8531057
TI  - Enduringness and change in creative personality and the prediction of
      occupational creativity.
AB  - Participants in a longitudinal study of women's adult development were scored at
      midlife on the Occupational Creativity Scale (OCS), which draws on J. L.
      Holland's (1985) model of vocational environments in the assessment of
      participants' creative achievement. College measures of cognitive-affective style
      and career aspirations predicted OCS scores at age 52, and consistency of
      creative temperament (H. G. Gough, 1992), motivation, and overall attributes of
      creative personality were demonstrated with both self-report and observer data
      over several times of testing. However, there was change along with this
      enduringness: Large fluctuations in creative temperament over one period of life
      or another were common in individuals, and OCS scores were associated with an
      increase in level of effective functioning over 30 years.

PMID- 8531058
TI  - Enhancing target variance in personality impressions: highlighting the person in
      person perception.
AB  - D. A. Kenny (1994) estimated the components of personality rating variance to be
      15, 20, and 20% for target, rater, and relationship, respectively. To enhance
      trait variance and minimize rater variance, we designed a series of studies of
      personality perception in discussion groups (N = 79, 58, and 59). After
      completing a Big Five questionnaire, participants met 7 times in small groups.
      After Meetings 1 and 7, group members rated each other. By applying the Social
      Relations Model (D. A. Kenny and L. La Voie, 1984) to each Big Five dimension at
      each point in time, we were able to evaluate 6 rating effects as well as rating
      validity. Among the findings were that (a) target variance was the largest
      component (almost 30%), whereas rater variance was small (less than 11%); (b)
      rating validity improved significantly with acquaintance, although target
      variance did not; and (c) no reciprocity was found, but projection was
      significant for Agreeableness.

PMID- 8531059
TI  - [Discovery and development of tamsulosin hydrochloride, a new alpha 1
      adrenoceptor antagonist].
AB  - Benign prostatic hyperplasia (BPH) is an age-related disorder characterized by
      urinary outlet obstruction. This obstruction is due to both mechanical
      compression of the urethra by the hypertrophied prostate and to functional
      contraction of the prostate and urethra by sympathetic stimulation. We invented a
      novel compound tamsulosin hydrochloride, a sulphamoylphenethylamine derivative
      which possesses potent and selective alpha a-antagonism, and showed that this
      compound selectively reduced the intra-urethral pressure in the prostatic segment
      of the urethra in vivo. We also found that the alpha 1-adrenoceptor plays an
      important functional role in the prostate and urethra. For clinical use, a
      control release formulation was developed. This formulation did not induce
      orthostatic hypotension and could be administered at a fixed dose. A placebo
      controlled double-blind dose finding study resulted in 0.2 mg/d as the optimal
      dose. This formulation significantly improved urinary outlet obstruction without
      affecting blood pressure as compared with placebo in P-III study, and was
      approved in 1993 for use in the treatment of bladder outlet obstruction
      associated with BPH. Tamsulosin hydrochloride is the first alpha 1-antagonist
      which improves bladder outlet obstruction associated with BPH without affecting
      blood pressure, and the treatment can be initiated and maintained at a fixed
      dose. Recently, the alpha 1-adrenoceptor subtypes alpha 1A, alpha 1B and alpha 1C
      were identified. The alpha 1C subtype is predominant and plays an important role
      in the human prostate. Tamsulosin hydrochloride shows high selectivity for this
      subtype, further supporting the clinical findings that tamsulosin hydrochloride
      improves bladder outlet obstruction associated with BPH with no effect on the
      cardiovascular system.

PMID- 8531060
TI  - [Chlorination and ozonation of contaminants in water environment and role of free
      radicals].
AB  - Pollutants in water environment are briefly reviewed concerning the water quality
      standard, especially the new items listed in the standard. They are disinfection
      byproducts, organohalogen compounds, and agrochemicals. Effects of chlorination
      and ozonation in the water treatment process on these contaminants and the
      contribution of the free radical to their toxicity are also discussed.
      Chlorination and ozonation in the water treatment process are believed to produce
      various active oxygen species, which seem to participate in the reaction with
      fumic acid, pollutants and bacteria. Main active oxygen species generated during
      the water treatment was a hydroxy radical, because DMPO-OH adduct was detected by
      the spin-trapping electron spin resonance (ESR) technique using 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO) as a spin-trapping reagent. Besides DMPO-OH, several
      DMPO adducts detected in both treatments were also described.

PMID- 8531061
TI  - [Species difference on binding property of dilazep to erythrocytes and
      platelets].
AB  - The whole blood of human, rabbit and dog spiked with dilazep was fractionated by
      discontinuous density gradients of Ficoll-Paque, and the species difference of
      distribution to blood components was elucidated. In order to quantitatively
      evaluate its blood distribution, the binding property of dilazep to the isolated
      erythrocytes and platelets was also studied. Dilazep undergoes saturable binding
      to the erythrocytes. Therefore, the fitting of the data sets to binding models
      was carried out using the nonlinear least-square method, and binding parameters
      were calculated. This technique could be also applied to analyze directly the
      binding parameters for several whole blood components. In human and rabbit,
      dilazep was bound to the erythrocytes with a high affinity (human, KERY = 0.466
      nM; rabbit, KERY = 0.0417 nM), however, the affinity to the erythrocytes in dog
      was very low. On the other hand, the binding affinity to the platelets decreased
      in the order of rabbit > dog > human.

PMID- 8531062
TI  - [Production of medicinal plants by soilless culture system. I. Studies of
      morphological characteristics and saikosaponins content in Bupleurum falcatum
      cultivated by Ebb & Flood system].
AB  - We studied that the morphological and histological characteristics, and the
      content (%DW) of saikosaponins on the root of Bupleurum falcatum cultivated in an
      Ebb & Flood system (E & F), a kind of soilless culture system, by both the direct
      sowing and the transplanting methods, and that effects of pinching on the root
      growth and the content (%DW) of saikosaponins in each part of root. Yield of root
      and content (%DW) of saikosaponins in each part of root, 8-months-old, cultivated
      in E & F by both methods were at the same level as that cultivated for the same
      period in soil condition by generally standard procedures. Morphological
      characteristics of the root cultivated by the direct sowing method were the same
      appearance as that by soil condition, but by the transplanting method main root
      branched off in all direction and the lateral root were more developed than by
      the direct sowing method. By pinching lignification in xylem on the main root
      were inhibited, but the dried weight of total root part and content (%DW) of
      saikosaponins in each part of the root were not shown to be significantly
      changed.

PMID- 8531063
TI  - [Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on low density
      lipoprotein in rabbits].
AB  - The hypolipidemic effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E)
      on cholesterol diet-fed rabbits were studied. EPA-E (300 mg/kg, p.o. x 4 weeks)
      decreased total cholesterols in the lipoprotein fractions of very low-density
      lipoprotein and intermediate lipoprotein+low-density lipoprotein (LDL), but not
      in high-density lipoprotein. Furthermore, the properties of LDL were investigated
      in rabbits given EPA-E (300 mg/kg, p.o. x 2 weeks). EPA-E had no influence on the
      lipid composition in LDL, and the cholesterol accumulation into macrophages was
      not increased by the incubation with EPA-E-treated LDL. However, the omega 3
      polyunsaturated fatty acids contents of LDL were increased by the administration
      of EPA-E. EPA-E-treated LDL was also studied on the binding to the hepatic
      membranes. The binding of EPA-E-treated LDL to the hepatic membranes was higher
      than that of ordinary LDL. These results suggest that EPA-E causes a modification
      of LDL, such that EPA-E has an enhancing effect on the hepatic uptake of LDL.
      These effects may contribute to the hypolipidemic action of EPA-E.

PMID- 8531064
TI  - [Study on Alpiniae Fructus. I. Pharmacological evidence of efficacy of Alpiniae
      Fructus on ancient herbal literature].
AB  - Pharmacological effects on anti-diuresis, anti-ulceration, anti-dementia and
      learning function of 50% ethanolic extract (AO-ext) from Alpiniae Fructus (fruit
      of Alpinia oxyphylla) removed seed vessel were investigated in order to prove the
      evidence of the efficacy of Alpiniae Fructus on the ancient herbal literature. AO
      ext showed the effects of anti-diuresis, anti-ulceration, anti-dementia and on
      increase in the learning function in animals. And also, AO-ext exhibited the
      increasing effect on the serum 11-hydroxycorticosteroid (11-OHCS) level in the
      above-described experimental animals and in intact and hypophysectomized rats.

PMID- 8531065
TI  - [Alkylation of gem-dibromocyclopropanes with higher-order organocuprates].
AB  - The reaction of gem-dibromocyclopropanes (1) with a higher-order organ-ocuprate
      prepared from CuCN and commercially available MeLi, followed by the addition of
      MeI in situ, afforded dimethylcyclopropanes (2) in good yields. The differential
      substitution reaction of dibromide (1a) in one pot with the higher-order
      organocuprate and allyl bromide gave a compound (8) in the moderate selectivity
      as shown in Table 3. Its stereochemistry was deduced by the reaction mechanism.

PMID- 8531066
TI  - The caffeine- and ryanodine-sensitive Ca++ store in porcine myometrial cells: its
      heterogeneity of all-or-none Ca++ release.
AB  - The mechanisms for Ca++ release from caffeine-sensitive stores were investigated
      in freshly dispersed porcine myometrial cells utilizing the fura-2 method.
      Because the caffeine-sensitive Ca++ store has not been detected in myometrium of
      mammals, we first determined the existence of this type of store in porcine
      myometrial cells. The evidence includes: 1) caffeine (1-33 mM)-induced
      concentration-dependent increase in the intracellular Ca++ concentration
      ([Ca++]i) in both the presence and absence of extracellular Ca++ and 2) although
      ryanodine alone (< or = 10 microM) failed to change [Ca++]i, it inhibited the
      response to caffeine in a use-, concentration- and time-dependent manner. In the
      cell suspension study, the amount of Ca++ released by 10 mM caffeine was found to
      be inversely proportional to the amount released by preadministration of caffeine
      (1-33 mM). In the single cell study, about 30% of cells responded to only a
      certain concentration of caffeine and the others responded to caffeine gradually.
      Thapsigargin, an inhibitor of Ca(++)-adenosine triphosphatase in sarcoplasmic
      reticulum, failed to increase [Ca++]i. Pretreatment with thapsigargin inhibited
      the response to caffeine in a time- and concentration-dependent manner. These
      results suggest that in porcine myometrial cells: 1) the Ca++ released from the
      caffeine- and ryanodine-sensitive store is in an all-or-none manner through
      compartments of stores or the entire store of a cell and 2) the release process
      is regulated by luminal Ca++ content of the stores.

PMID- 8531067
TI  - Endothelin ETA and ETB receptors facilitating parasympathetic neurotransmission
      in the rabbit trachea.
AB  - In the isolated rabbit trachea, electrical field stimulation (EFS) induced
      contraction that was inhibited by atropine or tetrodotoxin. Nonselective
      endothelin (ETA/ETB) receptor agonist, ET-1, relatively selective ETB receptor
      agonist, ET-3, and selective ETB receptor agonists, IRL 1620 and sarafotoxin S6c
      (STXc), augmented the EFS-induced contraction by 2- to 3-fold with similar EC50
      (0.4-1 nM). These agonists also showed direct contractile effect in the trachea.
      However, the threshold concentration of ET-1 (3 fM) to augment the electrical
      field stimulation-induced contraction was 100,000 times lower than that needed to
      directly stimulate smooth muscle. In contrast, these agonists did not augment the
      contraction induced by stimulation of muscarinic receptor by carbachol. An ETA
      receptor antagonist, BQ-123, was almost ineffective in antagonizing the effects
      of ET-1, ET-3 and STXc although if weakly antagonized the effects of IRL 1620. An
      ETB receptor antagonist, RES-701-1, antagonized the effects of ET-3 and IRL 1620
      without changing the effect of STXc and antagonized the effects of only lower
      concentrations of ET-1. In the trachea in which the ETB receptor was desensitized
      by strong activation, IRL 1620 and STXc were ineffective and ET-3 showed only
      small effect at higher concentrations. In contrast, the ETB desensitization
      inhibited the effects of only lower concentrations of ET-1. The effect of ET-1 in
      the ETB-desensitized trachea was partially, but not fully, antagonized by BQ-123.
      A potent ETB antagonist, BQ-788, showed similar effects to the ETB
      desensitization. These results suggest that ET-1 enhances nervous acetylcholine
      release by simultaneously activating the ET-1-selective ETA receptor and the
      isopeptide-nonselective ETB receptor (ETB1 subtype that is sensitive to both RES
      701-1 and BQ-788 and the ETB2 subtype that is sensitive only to BQ-788).

PMID- 8531068
TI  - Effects of chronic haloperidol on reaction time and errors in a sustained
      attention task: partial reversal by anticholinergics and by amphetamine.
AB  - The attentional and motor-disruptive effects of low doses of haloperidol were
      studied in a sustained attention task performed by rats. Five separate groups (n
      = 7 or 8) of rats were trained to react to a 0.125-sec visual stimulus by
      executing a nose-poke response within 3 sec of stimulus presentation. Each group
      of rats received its own dose (0.0, 0.02, 0.04, 0.08 or 0.12 mg/kg) of
      haloperidol daily for 3 months, and from the 1st week onward dose-effects on
      reaction time were quite stable across time. Haloperidol treatment disrupted the
      sustained attention task performance by decreasing the number of behavior
      initiated stimulus presentations, decreasing the number of reinforcers earned,
      increasing the proportion of errors of omission and increasing reaction time to
      the target stimulus. Testing of challenge drugs began after 23 days of
      haloperidol treatment. Scopolamine (0.1 and 0.2 mg/kg), benztropine (1.0, 3.0 and
      6.0 mg/kg) and d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) ameliorated
      haloperidol-induced reaction time slowing, whereas only benztropine and
      amphetamine lessened haloperidol-induced errors of omission. The 2.0-mg/kg dose
      of amphetamine by itself produced a significant increase in errors of omission
      without affecting reaction time. Haloperidol effectively normalized this
      amphetamine-induced disruption in attention. The results are consistent with a
      dopaminergic involvement in the expression of both attention and motor processes.

PMID- 8531069
TI  - H3-receptor activation inhibits cholinergic stimulation of acid secretion in
      isolated rabbit fundic glands.
AB  - We previously reported evidence for H3-receptor inhibition of cholinergic
      stimulation of acid secretion by isolated rabbit gastric glands. Because this
      inhibition was unsensitive to H2 antagonists, we postulated that the parietal
      cell should bear a H3-receptor. In the present study, we investigated the effects
      of M1-M3 muscarinic receptors antagonists on carbachol- and thioperamide-induced
      acid secretion (14CAP uptake) by isolated rabbit gastric glands. Furthermore, we
      examined whether H3-receptor ligands could affect [3H]-N-methylscopolamine
      binding to the isolated rabbit parietal cells. Both carbachol and thioperamide
      concentration-dependently stimulated 14CAP uptake in the glands with maximal
      responses being achieved for 100 microM and 0.1 microM, respectively. These
      stimulations were concentration-dependently inhibited by the H3-receptor agonists
      R(alpha)-methylhistamine and imetit. Maximal inhibitions did not exceed 60% for 1
      microM. The muscarinic receptor antagonists, hexa-sila-difenidol p-fluoro analog
      (M3), pirenzepine (M1) and gallamine (M2) inhibited carbachol-induced 14CAP
      uptake with IC50 of 50 nM, 10 microM and >> 100 microM, respectively.
      Thioperamide-induced 14CAP uptake was also inhibited by hexa-sila-difenidol p
      fluoro analog and pirenzepine with IC50 of 90 nM and 12 microM, respectively;
      whereas gallamine had no effect. [3H]-N-methylscopolamine binding to isolated
      parietal cells was inhibited by atropine and pFHHSiD with IC50 of 15 nM and 132
      nM, respectively. Neither R(alpha)-MeHA nor thioperamide did affect this binding
      although a H3-receptor inhibitory effect was observed on carbachol-induced 14CAP
      uptake by the cells. These data support that H3-receptor activation inhibits M3
      mediated cholinergic stimulation of acid secretion through mechanisms operating
      downstream to the receptors sites.

PMID- 8531070
TI  - Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice:
      pharmacological profile of protective and nonprotective agents.
AB  - Neurotoxic doses of methamphetamine (METH) can cause hyperthermia in experimental
      animals. Damage sustained to dopaminergic nerve terminals by this stimulant can
      be reduced by environmental cooling or by pharmacological manipulation which
      attenuates the hyperthermia. Many pharmacological agents with very diverse
      actions protect against METH-induced neuropathology. Several of these compounds,
      as well as drugs which do not protect, were investigated to determine if there
      was a relationship between protection and METH-induced hyperthermia. Mice
      received METH with or without concurrent administration of other drugs and core
      (i.e., colonic) temperature was monitored during treatment. The animals were
      sacrificed > or = 5 days later and neostriatal tyrosine hydroxylase activity and
      dopamine were measured. Core temperature was significantly elevated (> or = 2
      degrees C) in mice treated with doses of METH which produced > or = 90% losses in
      striatal dopamine but not in mice less severally affected (only 50% loss of
      dopamine). Concurrent treatment of mice with METH and pharmacological agents
      which protected partially or completely from METH-induced toxicity also prevented
      the hyperthermic response (i.e., dopamine receptor antagonists, fenfluramine,
      dizocilpine, alpha-methyl-p-tyrosine, phenytoin, aminooxyacetic acid and
      propranol). These findings are consistent with the hypothesis that the
      hyperthermia produced by METH contributes to its neuropathology. However, studies
      with reserpine, a compound which dramatically lowers core temperature,
      demonstrated that hyperthermia per se is not a requirement for METH-induced
      neurotoxicity. Although core temperature was elevated in reserpinized mice
      treated with METH as compared with reserpinized control mice, their temperatures
      remained significantly lower than in nonreserpinized control mice. However, the
      hypothermic state produced in the reserpinized mice did not provide protection
      from METH-induced toxicity. These data demonstrate that hyperthermia per se
      contributes to but is not solely responsible for the METH-induced neuropathology.

PMID- 8531071
TI  - Diabetes and ATP-sensitive potassium channel openers and blockers in isolated
      ischemic/reperfused hearts.
AB  - The incidence of reperfusion ventricular fibrillation (VF) and tachycardia (VT),
      heart function and the maldistribution of cardiac cations were studied in
      isolated ischemic/reperfused hearts obtained from streptozotocin-induced diabetic
      rats. Effects of an ATP-sensitive potassium (KATP) channel opener, cromakalim,
      and a KATP channel blocker, glibenclamide, also were studied. After 2 and 8 weeks
      of diabetes, hearts were isolated and subjected to 30 min of ischemia followed by
      reperfusion. After 2 weeks of diabetes, the incidence of VF and VT was reduced
      from their nondiabetic control values of 100 and 100 to 42% (P < .05) and 50% (P
      < .05), respectively. The reduction in VF and VT was not observed with
      progressive diabetes and after 8 weeks cardiac failure developed. In the 8-week
      diabetics, the development of cardiac failure was reflected in the aggravation of
      heart function (26, 16 and 17% reductions in aortic flow, left ventricular
      developed pressure and first derivative of developed pressure, respectively), and
      ion shifts (56 and 71% accumulation in cellular Na+ and Ca++, respectively, and
      15% loss in cell K+) before the induction of ischemia. After
      ischemia/reperfusion, these changes were pronounced in diabetic groups.
      Cromakalim aggravated and glibenclamide attenuated the incidence of arrhythmias,
      contractile function and ion shifts induced by ischemia/reperfusion in diabetic
      hearts. The data show that the use of KATP channel openers as anti-ischemic
      agents may be of particular concern in the population of postinfarction diabetic
      patients who are known to be at high risk of sudden coronary death.

PMID- 8531072
TI  - Relative vulnerability of dopamine and GABA neurons in mesencephalic culture to
      inhibition of succinate dehydrogenase by malonate and 3-nitropropionic acid and
      protection by NMDA receptor blockade.
AB  - The effects of different severities of metabolic stress on dopamine (DA) and
      gamma-aminobutyric acid (GABA) cell loss were examined in rat mesencephalic
      culture. Partial metabolic inhibition was induced in 12-day-old cultures by a 24
      hr treatment with various concentrations of 3-nitropropionic acid(3-NPA, 0.1-0.5
      mM) or malonate (10-50 mM), irreversible and reversible inhibitors of the Krebs
      cycle enzyme, succinate dehydrogenase. Cell damage to the DA and GABA populations
      was assessed after a 48-hr recovery period by simultaneous measurement of high
      affinity uptake for 3H-DA and 14C-GABA. 3-NPA or malonate caused a dose-dependent
      loss of DA uptake (EC50 0.21 or 42 mM, respectively). 3-NPA treatment was equally
      detrimental to the GABA population, whereas malonate exposure did not cause any
      significant loss of GABA uptake. The presence of the NMDA antagonist, MK-801 (1
      microM), during 24 hr of 3-NPA or malonate treatment fully protected against DA
      and GABA loss with 50 mM malonate or 0.25 mM 3-NPA and partially protected versus
      0.5 mM 3-NPA. To determine the degree of metabolic stress imposed by 3-NPA and
      malonate, 12-day-old cultures were treated with 0.5 mM 3-NPA or 50 mM malonate
      for 3 hr and the rate of lactate formation was measured. lactate was increased
      nearly 2-fold at 3 hr of treatment with 3-NPA, but was not significantly elevated
      above basal with malonate treatment. SDH activity was decreased by 48 or 58%
      after 3 hr of treatment with 0.25 and 0.5 mM 3-NPA, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8531073
TI  - Effect of fluoxetine, norfluoxetine, sertraline and desmethyl sertraline on human
      CYP3A catalyzed 1'-hydroxy midazolam formation in vitro.
AB  - The ability of fluoxetine, norfluoxetine, sertraline and desmethyl sertraline to
      inhibit the CYP3A subfamily of cytochromes P450 was examined in vitro, using the
      formation of 1'-hydroxy midazolam as a probe for CYP3A catalytic activity. The
      inhibition observed with these four compounds was modeled using competitive,
      noncompetitive, uncompetitive and mixed competitive/noncompetitive relationships
      by nonlinear regression analysis. The best fit model of the inhibition of CYP3A
      mediated 1'-hydroxy midazolam formation by all four compounds examined was
      determined to be mixed inhibition. The calculated Ki values were 65.7 +/- 12.0
      microM for fluoxetine, 19.1 +/- 1.9 microM for norfluoxetine, 64.4 +/- 11.6
      microM for sertraline and 48.1 +/- 11.6 microM for desmethyl sertraline. Steady
      state plasma levels of fluoxetine and norfluoxetine can approach a concentration
      of 1 microM (approximately 350 ng/ml of plasma). Assuming an inhibitor
      concentration of 1 microM and a concentration of the substrate substantially
      below its Km (at least 10-fold lower), the results reported predict that
      fluoxetine and norfluoxetine together would inhibit CYP3A catalytic activity by
      less than 7% (less than 0.7% if the unbound plasma concentration of fluoxetine is
      considered). By using the same assumptions and concentrations for sertraline and
      desmethyl sertraline, these agents together would be predicted to inhibit the
      metabolic clearance of a coadministered CYP3A metabolized drug by less than 4%.
      The observations reported here suggest that fluoxetine and sertraline would have
      little effect on CYP3A-mediated clearance of coadministered drugs.

PMID- 8531074
TI  - Effect of a new aminopeptidase P inhibitor, apstatin, on bradykinin degradation
      in the rat lung.
AB  - Bradykinin (Bk), a potent vasoactive and cardioprotective peptide hormone, is
      almost completely inactivated during a single circulation through the rat lung.
      It has been hypothesized that membrane-bound aminopeptidase P, which can
      hydrolyze the Arg1-Pro2 bond of Bk, and angiotensin-converting enzyme (ACE) act
      in concert to degrade Bk in the pulmonary circulation. To test this hypothesis,
      an inhibitor of aminopeptidase P was designed and synthesized. N-[(2S,3R)-3-amino
      2-hydroxy-4-phenylbutanoyl]-L-prolyl-L-prolyl-L - alaninamide (apstatin)
      inhibited purified rat lung membrane-bound aminopeptidase P with a Ki value of
      2.6 microM (linear mixed-type inhibition, alpha = 5.1, beta = 0). Apstatin did
      not inhibit ACE or other known Bk-degrading enzymes. Apstatin and an ACE
      inhibitor, ramiprilat, were tested for their ability to inhibit Bk degradation in
      the isolated perfused rat lung. [2,3-Proly-3,4-3H(N)]-bradykinin ([3H]-Bk) was
      perfused through the isolated lung in the presence or absence of inhibitors. The
      perfusate was then subjected to HPLC to identify and quantitate radiolabeled
      fragments. In the absence of inhibitors, no intact [3H]-Bk was found in the
      perfusate. In the presence of ramiprilat (0.5 microM), only 22% +/- 6% of the
      radioactivity in the perfusate was intact [3H]-Bk, and the remaining
      radioactivity indicated cleavage of the Arg1-Pro2 bond. When apstatin (40 microM)
      was perfused along with ramiprilat, degradation of [3H]-Bk was almost completely
      blocked (92% +/- 4% intact [3H]-Bk in the perfusate). The results indicate that
      the Bk-degrading activity in the rat pulmonary vascular bed can be fully
      accounted for by aminopeptidase P (30%) and ACE (70%).

PMID- 8531075
TI  - Endothelin subtypes: effect on isolated rhesus monkey ciliary muscle.
AB  - The effects of endothelin (ET)-1, ET-2, ET-3 and sarafotoxin S6C on the
      contractile response in the longitudinal and coronal vectors of the isolated
      rhesus monkey ciliary muscle were studied. Fresh ciliary muscle strips from young
      and middleaged rhesus monkeys were mounted in an apparatus capable of monitoring
      contractile force simultaneously in the two vectors. The responses to the ET
      compounds were measured and compared to those produced with 1 microM carbachol.
      ET-1 produced contractions of up to 15% of the near-maximum response to carbachol
      in both vectors of 66% of ciliary muscle strips studied. In responsive strips,
      the maximal ET-1 induced contraction was approximately equal in both vectors, but
      the longitudinal vector was approximately 5-fold more sensitive than the
      circular. All ciliary muscle strips responded reproducibly to carbachol. None of
      the other ET compounds tested had any effect, suggesting that the ETA receptor
      may predominate in rhesus monkey ciliary muscle. Because ET-1 induces only weak
      and interindividually variable contraction in isolated rhesus monkey ciliary
      muscle strips, ET-1's enhancement of outflow facility with only minimal induction
      of accommodation in the living monkey may be due to effects directly on the
      trabecular meshwork. However, the 5-fold greater potency of ET-1 in the
      longitudinal compared to the circular contractile vector may indicate that
      selective contraction of the longitudinal portion of the ciliary muscle with
      consequent deformation of the trabecular meshwork but not the lens is also
      involved.

PMID- 8531076
TI  - Ischemic preconditioning, adenosine and bethanechol protect spontaneously
      hypertensive isolated rat hearts.
AB  - The frequency of chronic hypertension among cardiac surgery patients implies that
      experimental therapies that protect normotensive myocardium will be more
      clinically relevant if they also protect chronically hypertensive myocardium. We
      tested the effectiveness of three experimental therapies that protect
      normotensive myocardium from ischemic injury in both normotensive (NTR) and
      spontaneously hypertensive (SHR) isolated Sprague-Dawley rat hearts. Post
      ischemic recovery of ATP, left ventricular end diastolic pressure, developed
      pressure, negative and positive left ventricular dP/dt (-dP/dt and +dP/dt) and
      coronary flow (CF) were compared in ischemically preconditioned, adenosine
      pretreated, bethanechol-pretreated and untreated NTR and SHR isolated rat hearts.
      The effect of time on our preparation was evaluated by comparison to NTR and SHR
      hearts maintained in vitro for equal duration but not subjected to an ischemic
      insult (N = 7, all groups). Preconditioning, adenosine and bethanechol
      significantly improved recovery of ATP, left ventricular end diastolic pressure,
      developed pressure, -dP/dt, +dP/dt and coronary flow in both NTR and SHR hearts
      (P < 0.001 vs. untreated, all comparisons). Although recovery was not so
      pronounced in SHR hearts, these results suggest that experimental therapies that
      protect normotensive myocardium also protect chronically hypertensive myocardium.
      The effect of adenosine and that of ischemic preconditioning were nearly
      identical, and both treatments were significantly more cardioprotective than
      bethanechol in both NTR and SHR hearts (P < .05 and P < .001, respectively). This
      result suggests that adenosine buildup is more important than muscarinic receptor
      stimulation as a mechanism of the protection afforded by ischemic
      preconditioning.

PMID- 8531077
TI  - Intervessel (arteries and veins) and heart/vessel selectivities of
      therapeutically used calcium entry blockers: variable, vessel-dependent indexes.
AB  - The intervessel selectivity indexes of the calcium entry blockers amlodipine,
      felodipine, isradipine, nicardipine, nifedipine, nitrendipine, diltiazem and
      verapamil were assessed by determining the potency of these compounds
      [concentration decreasing tension developed by KCl in blood vessels by 50%
      (bvlC50)] to relax several KCl-precontracted blood vessels (femoral, jugular and
      saphenous veins and left anterior descending and left circumflex coronary and
      renal arteries) precontracted with KCl. The concentrations of KCl (25 mM for
      arteries and 50 mM for veins) used gave a similar response in these vessels.
      Intervessel selectivity indexes are the ratios of the bvlC50 determined in two
      different vessels. The negative inotropic potency (hlC50) was ascertained in
      paced (2 Hz), isoproterenol-(10 nM) supported atrial strips, and for three of the
      compounds, in papillary muscles. This allowed calculation of heart/vessel
      selectivity or vasoselectivity (ratio of hlC50 and bvlC50). All compounds
      overcame almost entirely (85-100%) the vessel contractile response to KCl and
      strongly reduced (65-90%) the tension developed by myocardial preparations. The
      rank order for vasorelaxant potency (bvlC50 from approximately 1 to approximately
      700 nM) was generally as follows: isradipine > or = nifedipine > or =
      nitrendipine > or = amlodipine > or = verapamil > or = felodipine > or =
      nicardipine > or = diltiazem. However, the rank order for negative inotropic
      potency (hlC50 spanning from approximately 200 to approximately 6000 nM) was
      isradipine > or = nifedipine > or = verapamil > or = diltiazem > or = amlodipine
      > or = nitrendipine > or = felodipine > or = nicardipine. All compounds were
      generally more potent in relaxing capacitance than conductance vessels.
      Furthermore, of the capacitance vessels, the jugular vein was the least
      susceptible to relaxation; among the conductance vessels, five of the eight
      compounds relaxed renal arteries with greater potency than coronary arteries.
      Consequently, the value of the heart/vessel selectivity index is intrinsically
      dependent on the vessel used to calculate it. Overall, nitrendipine was the most
      vasoselective calcium entry blocker studied, with selectivity indexes ranging
      from 28 to 523. In conclusion, 1,4-dihydropyridine calcium entry blockers
      generally have a much greater affinity for calcium channels present in micropig
      veins than in heart muscle myocytes. This is possibly due to tissue-specific
      features of L-type calcium channels. Finally, comparing the vasoselectivity index
      of various compounds has validity only if this index is calculated by using the
      same experimental procedure applied to the same vascular tissue and the same
      heart preparation taken from the same species.

PMID- 8531078
TI  - 1,3-Dipropyl-8-[2-(5,6-epoxy)norbornyl]xanthine, a potent, specific and selective
      A1 adenosine receptor antagonist in the guinea pig heart and brain and in DDT1MF
      2 cells.
AB  - The objective of this study was to characterize the adenosine receptor (AdoR)
      antagonistic properties of a newly synthesized alkylxanthine, 1,3-dipropyl-8[2
      (5,6-epoxy)norbornyl]xanthine (ENX), and compare them to those of 1,3-dipropyl-8
      (cyclo-pentyl)xanthine (CPX), 1,3-dipropyl-8-(3-noradamantyl)xanthine (NAX) and
      (+/-)-N6-endo-norbornan-2-yl-9-methyladenine (N-0861). The potencies and
      selectivities of ENX, CPX, NAX and N-0861 were determined by functional studies
      of guinea pig isolated perfused hearts, and by radioligand binding assays for A1
      and A2a AdoRs in the guinea pig forebrain and striatum. ENX competitively
      antagonized A1 AdoR-mediated prolongations of atrioventricular nodal conduction
      time caused by Ado or by 2-chloro-N6-cyclopentyladenosine, but not those caused
      by carbachol (0.14 microM) or MgCl2 (3 mM). Schild analysis of 2-chloro-N6
      cyclopentyladenosine-antagonist competition curves yielded pA2 values for ENX,
      CPX and NAX of 8.45 +/- 0.19, 8.55 +/- 0.28 and 8.79 +/- 0.15, respectively. ENX
      (30 microM) and N-0861 (30 microM) did not attenuate the A2 AdoR-mediated
      increase in coronary conductance caused by adenosine. CPX and NAX attenuated the
      coronary vasodilation caused by adenosine with IC50 values of 1.5 and 7.1 microM,
      respectively. Radioligand binding assays revealed that ENX, CPX and NAX and N
      0861 had a 400-, 209-, 110- and 10-fold greater affinity, respectively, for A1
      than for A2a AdoRs of guinea pig brain membranes. Thus, ENX was equipotent with
      CPX and NAX and more potent than N-0861 (pA2 = 6.2) as an antagonist at A1 AdoRs,
      but had lower affinity for A2 AdoRs in guinea pig hearts and brain striatum than
      did either CPX or NAX. In DDT1 MF-2 cells, all three alkylxanthines had similar
      affinities for A1 AdoRs, whereas the affinity of N-0861 for A1 AdoRs was
      significantly lower. ENX appears to be the most A1 AdoR subtype-selective of the
      alkylxanthine class of AdoR antagonists reported to date.

PMID- 8531079
TI  - Accumulation of protein-coated liposomes in an extravascular site: influence of
      increasing carrier circulation lifetimes.
AB  - The primary objective of this work was to test whether increased blood levels and
      circulation lifetimes result in increased passive targeting of protein-coated
      liposomal drug carriers. The system used to evaluate this was based on i.v.
      injection of 100 nm of distearoyl phosphatidylcholine/cholesterol liposomes with
      covalently bound streptavidin. The circulation lifetime of these liposomes was
      increased by procedures that involved blockade of liposome uptake by phagocytic
      cells in the liver and/or the incorporation of a poly(ethylene glycol)-modified
      phospholipid [poly(ethylene glycol)2000-modified distearoyl
      phosphatidylethanolamine]. Blockade of liver phagocytic cells with a low predose
      (2 mg/kg of drug) of liposomal doxorubicin increased the circulation half-life of
      the streptavidin liposomes from less than 1 hr to greater than 3 hr. A further 2
      fold increase in circulating half-life (to approximately 7.5 hr) was achieved by
      using liposomes with 2 mole % of poly(ethylene glycol)2000-modified
      phosphatidylethanolamine. In combination with RES blockade, the circulation
      lifetimes of poly(ethylene glycol)phosphatidylethanolamine containing
      streptavidin liposomes could be increased to greater than 12 hr. The ability of
      these liposomes to move from the plasma compartment to an extravascular
      compartment was measured by using the peritoneal cavity as a convenient,
      accessible, extravascular site. The tendency for liposomes to accumulate in this
      site was not, however, clearly dependent on circulating blood levels. Comparable
      levels of liposomes in the peritoneal cavity were achieved when using systems
      that exhibited significantly different circulation lifetimes.

PMID- 8531080
TI  - Pharmacodynamic model for acute tolerance development to the
      electroencephalographic effects of alfentanil in the rat.
AB  - This investigation was carried out to characterize the rate and extent of acute
      tolerance development to the pharmacodynamics of alfentanil in the rat with the
      electroencephalogram (EEG) as a measure of alfentanil's effects on the central
      nervous system. Alfentanil was administered by use of three different drug
      infusion strategies in order to develop a pharmacokinetic-pharmacodynamic model
      for acute tolerance: I) intravenous infusion of 0.5 mg/kg in 10 min, achieving
      peak alfentanil concentrations of 750 ng/ml; II) computer-controlled infusion to
      rapidly achieve and maintain a constant drug level of 750 ng/ml, followed by
      washout; III) computer-controlled infusion to step through multiple constant drug
      levels (up to 1500 ng/ml), followed by washout. Frequent arterial plasma samples
      were taken and assayed for alfentanil. EEG signals were continuously recorded
      until effects returned to base-line values. The amplitudes in the 0.5- to 3.5-Hz
      (delta) frequency band were calculated by aperiodic analysis and used as an EEG
      effect measure. The pharmacokinetic data were characterized by a three
      compartment model with nonlinear clearance. Nonlinear kinetics was apparent from
      the multiple steady-state protocol III. Clearance values ranged from (S.E.) 49.7
      (2.8) ml/min/kg at low alfentanil concentrations to a minimum value of 29.3 (0.8)
      ml/min/kg at high concentrations. The pharmacodynamic data showed profound acute
      tolerance development reflected as proteresis in the concentration-effect pairs
      after protocol I and a rapidly declining effect in the presence of stable
      alfentanil concentrations after protocols II and III. The effect stabilized
      within 15 min after a change in target concentration. A physiological tolerance
      model was developed to characterize the rate and extent of tolerance development
      to the effects of alfentanil. The models are generally applicable and consider
      the physiological homeostatic mechanisms responsible for the tolerance
      development to be an integral part of the pharmacodynamic system. Tolerance was
      modeled as a negative feedback control of the drug-induced effect with a first
      order transfer function. The model required only two tolerance parameters to
      quantify the rate and extent of tolerance development and allowed for a rebound
      effect. Maximum tolerance diminished alfentanil's effect by 46% and was achieved
      with a half-life of 7.0 min.

PMID- 8531081
TI  - Striatal dopamine receptors and adenylyl cyclase activity in a rat model of
      alcohol addiction: effects of ethanol and lisuride treatment.
AB  - In this report a novel animal model of spontaneous development of alcohol and
      drug addiction was used. Addiction to ethanol was induced in male Wistar rats
      (free choice between ethanol solutions and water for 11 mo). After 36 wk of
      alcohol deprivation these rats (series A) had ingested 3.4 +/- 0.4 g
      ethanol/kg/day. Age-matched, "controlled" alcohol consumers (series C: free
      choice for 8 wk) had ingested only 1.6 +/- 0.4 g/kg/day (P < .001). Two
      additional series of addicted (AL) and controlled alcohol-consuming rats (CL)
      received lisuride (90 micrograms/kg/day) for 8 wk concomitantly with the self
      administered ethanol and again during the last week before death. Ethanol intake
      was increased by lisuride treatment in both groups (AL: 4.1 +/- 0.3 g/kg/day; CL:
      2.7 +/- 0.4 g/kg/day; P < .05). Four months before death the alcohol was
      withdrawn. After this period of abstinence the in vitro dose-response curves for
      striatal dopamine D-1 receptor-stimulated adenylyl cyclase activity were
      determined (with eight concentrations of dopamine between 50 nM and 30 microM).
      Both lisuride-treated (AL) and untreated ethanol-addicted rats (A) displayed a
      significant (P < .01) increase in the effective concentration required to induce
      50% of the response (EC50) as compared with controlled drinkers (C: 720 +/- 150
      nM; A: 1820 +/- 390 nM; CL: 590 +/- 110 nM; AL: 1050 +/- 160 nM). Lisuride
      treatment increased forskolin- (10 microM) stimulated adenylyl cyclase activity
      and the Bmax of high-affinity [3H]DA binding to the D-1 site.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8531082
TI  - Suppression by mycophenolate mofetil of the neointimal thickening caused by
      vascular injury in a rat arterial stenosis model.
AB  - Injury of the rat carotid artery by gentle perfusion of air causes vascular
      thickening, similar to that seen in the clinic setting in humans after
      percutaneous angioplasty or bypass surgery to repair injured or diseased blood
      vessels. In the animal model as well as in patients, this stenosis appears to be
      the result of smooth muscle cell migration and proliferation. Various cell types
      in the lesion area may contribute by producing inflammatory cytokines, adhesion
      molecules and growth factors. In the present study, mycophenolate mofetil (MMF),
      an inosine monophosphate dehydrogenase inhibitor with antiproliferative and
      immunosuppressive properties, was tested for its ability to inhibit this process.
      With a daily oral dose of 30 mg MMF/kg started 6 days before injury to one
      carotid artery by air perfusion, MMF reduced cross-sectional areas of total
      vessel wall (intima-media) thickness by 17% to 25% and of neointimal thickness by
      48% to 60% at 14 days after injury in four tests (P < .001 when MMF- and vehicle
      treated groups were compared for these thickened areas, n = 29 or 30). In
      addition, intima/media ratios ranged from 0.26 +/- 0.03 to 0.46 +/- 0.04 for MMF
      treated vs. 0.55 +/- 0.05 to 0.93 +/- 0.08 for vehicle-treated animals in the
      four different tests (P < .001). Starting MMF treatment at either 14 or 0 days
      before arterial injury made no difference in the degree of reduction, suggesting
      that any biological process that might be altered by MMF is not one that requires
      much time to become established. Intima/media ratios were 0.31 +/- 0.04 or 0.34
      +/- 0.04 for MMF-treated vs. 0.55 +/- 0.05 or 0.65 +/- 0.07 for vehicle-treated
      animals (P < .001 for day 14 or 0, respectively, n = 30). Thus, MMF reduced the
      vascular thickening after carotid artery injury in rats, suggesting that this
      class of compound may be able to control the pathological processes that lead to
      restenosis.

PMID- 8531083
TI  - Pharmacology of 5-chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione: a
      novel systemically active ionotropic glutamate receptor antagonist.
AB  - 5-Chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1011) has
      analgesic properties in animal models of tonic pain. To investigate the
      mechanisms underlying this effect we used electrical recording techniques to
      characterize the in vitro pharmacology of ACEA-1011 at mammalian glutamate
      receptors. Two preparations were used: Xenopus oocytes expressing rat brain
      receptors and cultured rat cortical neurons. Results showed that ACEA-1011 is a
      competitive antagonist at NMDA receptor glycine sites. Apparent antagonist
      affinities (Kb values) were 0.4 to 0.8 microM in oocytes and approximately 0.6
      microM in neurons. IC50 values for ACEA-1011 against four binary subunit
      combinations of cloned rat NMDA receptors (NR1A/NR2A, 2B, 2C or 2D) ranged from
      0.4 to 8 microM (1 microM glycine). The 20-fold variation in sensitivity was due
      to a combination of subunit-dependent differences in glycine and antagonist
      affinities; EC50 values for glycine ranged between 0.08 to 0.8 microM and Kb
      values for ACEA-1011 between 0.2 to 0.8 microM. In addition, ACEA-1011 inhibited
      AMPA-preferring non-NMDA receptors by competitive antagonism at glutamate binding
      sites. Kb values were 4 to 9 microM in oocytes and 9 to 10 microM in neurons. The
      ED50 for ACEA-1011 in a mouse maximum electroshock-induced seizure model was
      approximately 12 mg/kg i.v.. Our results indicate that ACEA-1011 is a
      systemically active broad selectivity ionotropic glutamate receptor antagonist.

PMID- 8531084
TI  - Hypoxic relaxation in functionally intact cattle coronary artery segments
      involves K+ ATP channels.
AB  - Functionally intact coronary artery segments studied in vitro responded to 15 min
      of hypoxia with relaxations of preexisting contractions. The hypoxic relaxations
      were obtained in preparations routinely denuded of endothelium and were
      unaffected by tetrodotoxin, by indomethacin or by the blockers of calcium
      dependent potassium channels, apamin and charybdotoxin. Relaxations from
      contractions to the calcium channel opener Bay K 8644 and to spontaneous tone
      were attenuated most by hypoxia, and those to carbamylcholine and 5
      hydroxytryptamine were inhibited to an intermediate extent. Contractions to the
      thromboxane A2 analog U 46619, dependent largely on intracellular calcium, were
      the least reduced during 15 min of hypoxia. Pretreatment of contracted
      preparations with glibenclamide, the potent antagonist of ATP-dependent potassium
      channels, before exposure to 95% N2/5% CO2 significantly attenuated, but did not
      eliminate, hypoxic relaxations. Hypoxic relaxations from contractions to the
      calcium channel opener Bay K 8644 and to spontaneous tone were antagonized most
      by glibenclamide, and those to U 46619 were reduced the least. In the presence of
      the calcium channel antagonist nifedipine, tissues contracted with
      carbamylcholine or 5-hydroxytryptamine relaxed during hypoxia, but these
      relaxations were insensitive to glibenclamide. Contractions of cattle radial
      artery and rabbit aorta were variably reduced during hypoxia but were insensitive
      to glibenclamide. We conclude that K+ ATP channels participate in hypoxia-induced
      coronary artery smooth muscle relaxation and may do so particularly with
      contractions that utilize principally extracellular calcium.

PMID- 8531085
TI  - A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced
      endothelial cell injury, in vitro.
AB  - There is an increased interest in development of therapeutic agents to treat
      disease states that involve reactive oxygen species in their pathophysiology. The
      metalloporphyrins, MnTBAP and ZnTBAP, were found to be active in a superoxide
      dismutase (SOD) assay. The efficacy of these compounds were tested against a well
      established model of intracellular superoxide-mediated cell injury. Paraquat
      generates superoxide by redox cycling with intracellular diaphorases and
      molecular oxygen. SOD mimetics were employed in a cell culture model with calf
      pulmonary artery endothelial cells (CPA-47) grown to near confluence in 24-well
      plates. Cell injury was assessed by measuring the release of cytosolic lactate
      dehydrogenase into the cell medium and by the number of adherent cells remaining
      after treatment. Exposure to various concentrations of paraquat for 4 h produced
      a dose-dependent injury response that was attenuated by 50 microM SOD mimetic,
      MnTBAP. MnTBAP also protected endothelial cells in a dose-dependent manner (EC50
      approximately 40 microM) against paraquat (2 mM), whereas its less active analog
      (ZnTBAP) did not protect them. The protective effect of MnTBAP appears to be due
      to its intracellular superoxide-scavenging activity because neither the zinc form
      or exogenous CuZnSOD protected the cells against paraquat-induced injury. These
      studies suggest that metalloporphyrin-based SOD mimetics may be useful agents in
      preventing injury and disease states associated with the generation of
      intracellular reactive oxygen species.

PMID- 8531086
TI  - Pharmacological evaluation of selected, orally active, peptidyl inhibitors of
      human neutrophil elastase.
AB  - Human neutrophil elastase (HNE) is a serine proteinase capable of degrading a
      number of connective tissue macromolecules and has been implicated in the
      destructive processes associated with several chronic inflammatory diseases. A
      large series of peptidyl electrophilic ketones have been shown to be potent
      inhibitors of HNE in vitro and in vivo. We report the pharmacology and
      pharmacokinetics of selected inhibitors from this series. MDL 101, 146, MDL 102,
      111, MDL 102,823 and MDL 100,948A are -Val-Pro-Val-pentafluoroethylketones with
      various amino-terminal protecting groups. Although their Ki values varied
      considerably, (25-170 nM), these compounds demonstrated similar ED50 values after
      oral administration in the HNE-induced hemorrhage model in hamsters and rats. The
      duration of action of MDL 102,111 was shorter than that of the other analogs in
      the HNE-induced pulmonary hemorrhage model in both species. The duration of
      action of all of the compounds was longer in the rat than in the hamster.
      Isolated sections of rat jejunum were used to determine the in situ absorption of
      these compounds. MDL 102,111 showed the greatest extent of absorption, with MDL
      102,823, MDL 100,948A and MDL 101,146 following in descending rank order. The
      comparative metabolic stability of these analogs was measured over a 2-hr
      incubation period using rat liver homogenates. MDL 101,146 was the most stable,
      followed by MDL 102,823, MDL 102,111 and MDL 100,948A. MDL 101,146 was more
      stable in a liver homogenate from rats compared with a liver homogenate from
      hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531087
TI  - Nafadotride, a potent preferential dopamine D3 receptor antagonist, activates
      locomotion in rodents.
AB  - Nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyano naphtalene-2
      carboxamide) is a novel compound, which inhibits potently and stereoselectively
      [125I]iodosulpride binding at recombinant human dopamine D3 receptors. the
      levoisomer displays an apparent Ki value of 0.3 nM at the dopamine D3 receptor,
      but is 10 times less potent at the human recombinant dopamine D2 receptor. In
      comparison, the dextroisomer displays 20-fold less apparent affinity at the
      dopamine D3 receptor and reduced (2-fold) selectivity. l-Nafadotride displays
      iow, micromolar affinity at dopamine D1 and D4 receptors and negligible apparent
      affinity at various other receptors. In dopamine D3 receptor-transfected NG-108
      15 cells, in which dopamine agonists increase mitogenesis, l-nafadotride has no
      intrinsic activity, but competitively antagonizes the quinpirole-induced
      mitogenetic response, monitored by [3H]thymidine incorporation with a pA2 of 9.6.
      In dopamine D2 receptor-transfected Chinese Hamster Ovary cells, l-nafadotride
      also behaves as a competitive antagonist of quinpirole-induced mitogenesis with
      an 11-fold lower potency. These studies establish nafadotride as a pure,
      extremely potent, competitive and preferential dopamine D3 receptor antagonist in
      vitro. l-Nafadotride displaces in vivo N-[3H]propylnorapomorphine accumulation at
      lower dosage and for longer periods in limbic structures, containing both
      dopamine D2 and D3 receptors than in the stratum, containing dopamine D2 receptor
      only. At low dosage (0.1-1 mg/kg), nafadotride, unlike haloperidol, a dopamine D2
      receptor-preferring antagonist, increases spontaneous locomotion of habituated
      rats and climbing behavior of mice, at doses that do not modify striatal
      homovanillic acid levels. At high dosage (1-100 mg/kg), nafadotride, like
      haloperidol, produces catalepsy and antagonizes apomorphine-induced
      climbing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531088
TI  - Vasorelaxing effect of S-nitrosocaptopril on dog coronary arteries: no cross
      tolerance with nitroglycerin.
AB  - S-Nitrosocaptopril (S-NO-Cap) produced dose-dependent relaxation in isolated dog
      coronary arteries. This relaxation consisted of two parts: an initial phasic
      relaxation and a subsequent sustained relaxation. Relaxation was potentiated by
      superoxide dismutase but was suppressed by pyrogallol, methylene blue or
      oxyhemoglobin. The relaxant responses of coronary artery to vasoactive agents
      were reexamined after the development of nitrate tolerance induced by a 1-hr
      treatment with 4.4 x 10(-4) M nitroglycerin (NTG). NTG tolerance was verified by
      a 40-fold increase in the EC50 values. The relaxant response to nitroprusside was
      only marginally suppressed in NTG-tolerant arteries. NTG-tolerant arteries were
      not tolerant to nitric oxide (NO) or 8-bromo-cyclic guanosine monophosphate
      (cGMP) and did not show a significant change in the concentration-response
      curves. Similarly, the concentration-response curves for S-NO-Cap in NTG-tolerant
      coronary arteries were not significantly different from those in nontolerant
      coronary arteries. Captopril (5 x 10(-4) M) did not enhance the vasodilative
      effect of NTG or reverse NTG tolerance. The NTG-induced increase in cGMP was
      abolished after NTG tolerance was established. On the other hand, the S-NO-Cap
      induced increase in cGMP was unaffected by NTG tolerance. In conclusion, these
      findings indicate that (1) S-NO-Cap is an NO-like substance, (2) an impaired
      formation of NO or S-nitrosothiol is responsible for the formation of NTG
      tolerance and (3) S-NO-Cap, which does not show cross-tolerance with NTG, may
      serve as a therapeutic alternative to current nitrovasodilators.

PMID- 8531089
TI  - Growth inhibitory effects on human colon adenocarcinoma-derived Caco-2 cells and
      calcemic potential of 1 alpha,25-dihydroxyvitamin D3 analogs: structure-function
      relationships.
AB  - A panel of synthetic analogs of 1 alpha,25-dihydroxyvitamin D3 [1
      alpha,25(OH)2D3] bearing one or multiple structural modifications at functionally
      or metabolically sensitive positions of the molecule, i.e., C-1, 16, 23, 26 and
      27, were tested for their growth inhibitory and prodifferentiating potency in
      human colon adenocarcinoma-derived Caco-2 cells. With respect to the peak
      response elicited at 10(-8) M, 1 alpha,25-dihydroxy-16-ene-vitamin D3, 1 alpha,25
      dihydroxy-23-yne-vitamin D3 and 1 alpha,25-dihydroxy-16,23Z-diene-vitamin D3
      suppressed [3H]thymidine incorporation in confluent Caco-2 cells less than 1
      alpha,25(OH)2D3. 1 alpha,25-dihydroxy-16,23e-diene-vitamin D3 was at least
      equipotent to the parent compound, whereas 1 alpha,25-dihydroxy-16-ene-23-yne
      vitamin D3 and most conspicuously 1 alpha,25-dihydroxy-26,27-hexafluoro-16-ene-23
      yne- vitamin D3 reduced growth of Caco-2 cells to significantly (P < .05) lower
      levels than 1 alpha,25(OH)2D3. The same rank order was obtained for the ability
      of the vitamin D compounds to induce activity of the differentiation marker
      enzyme, alkaline phosphatase, in quiescent Caco-2 cells. Whereas the effect of
      the synthetic analogs on calcium uptake by cultured embryonic chick duodenum in
      general was less pronounced than that of 1 alpha,25(OH)2D3, the two most potent
      antimitogenic compounds, 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 and 1
      alpha,25-dihydroxy-26,27-hexafluoro-16-ene-23-yne-vitamin D3, elicited calcium
      mobilization from cultured neonatal mouse calvaria at a 10-fold lower
      concentration than the parent compound.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531090
TI  - Pharmacological evaluation of 1229U91, a novel high-affinity and selective
      neuropeptide Y-Y1 receptor antagonist.
AB  - The physiological role of neuropeptide Y (NPY), peptide YY (PYY) and their
      receptors (Y1 and Y2) has been difficult to elucidate mainly due to the lack of
      selective and high-affinity antagonists. Recently, Burroughs Wellcome disclosed a
      series of cyclic peptides, including the compound 1229U91, which were reported to
      be selective NPY receptor antagonists (PCT Publication No. WO 94/00486). The
      objective of this study was to evaluate the pharmacological properties of
      1229U91. In radioligand binding studies, 1229U91 displaced specifically bound
      [125I]PYY from SK-N-MC cells (Y1 receptors) and SK-N-BE(2) cells (Y2 receptors)
      yielding pKi +/- S.E.M. estimates of 10.9 +/- 0.2 and 7.9 +/- 0.2, respectively.
      In the isolated perfused kidney of rat (Y1 receptor assay), NPY (10-1000 ng,
      bolus injection) evoked concentration-dependent increases in perfusion pressure
      (EC50 = 54.5 ng). In this assay, 1229U91 (1, 10 and 100 nM) produced
      concentration-dependent dextral displacement of the concentration-effect curve to
      NPY. The antagonism was surmountable at 1 nM 1229U91 (apparent pA2 estimate +/-
      S.E.M. = 9.3 +/- 0.4). At concentrations of 10 and 100 nM, 1229U91 produced
      significant depression of the maximum response to NPY (36 and 67%, respectively).
      In the vas deferens of rat (Y2 receptor assay), 1229U91 (3 microM) had no effect
      on NPY-induced inhibition of electrically evoked twitch response. In pithed rats,
      1229U91 (0.3, 1 and 3 micrograms/kg/min i.v.) produced dose-dependent dextral
      displacement of the pressor dose-response curve to NPY yielding dose-ratio
      estimates of 2.4, 25.4 and 57.5, respectively. 1229U91 (3 micrograms/kg/min i.v.)
      had no effect on the pressor responses to norepinephrine or angiotensin
      II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531091
TI  - Discriminative stimulus effects of R-(+)-3-amino-1-hydroxypyrrolid-2-one, [(+)-HA
      966], a partial agonist of the strychnine-insensitive modulatory site of the N
      methyl-D-aspartate receptor.
AB  - The strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA)
      receptor complex is a target for development of a host of therapeutic agents
      including anxiolytics, antidepressants, antiepileptics, anti-ischemics and
      cognitive enhancers. In the present experiments, the discriminative stimulus
      effects of (+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2-one], a low-efficacy
      partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were
      trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T-maze under
      which behavior was controlled by food. Other glycine partial agonists, 1-amino-1
      cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the
      discriminative stimulus effects of (+)-HA-966 despite known differences in other
      pharmacological effects of these compounds. The glycine site antagonist, 7
      chlorkynurenic acid, did not substitute for (+)-HA-966. Likewise other functional
      NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not
      substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel
      blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1, 2
      cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil,
      substituted for (+)-HA-966. Although the full agonist, glycine, did not
      substitute, this compound fully blocked the discriminative stimulus effects of
      (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of
      dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizoclipine
      appropriate responses. These data suggest that the discriminative stimulus
      effects of (+)-HA-966 are based upon its partial agonist actions at the
      strychnine-insensitive glycine site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531092
TI  - Pharmacology of a constitutively active muscarinic receptor generated by random
      mutagenesis.
AB  - We have isolated a mutant m5 muscarinic receptor that mediates robust functional
      responses in the absence of agonists. This constitutively active receptor was
      isolated from a library of receptors containing randomly introduced mutations in
      the sixth transmembrane domain and contains the substitutions serine 465 for
      tyrosine and threonine 486 for proline. Although these individual residues are
      not conserved in other G-protein-coupled receptors, they are predicted to be at
      the junction between the sixth transmembrane domain and the last extracellular
      loop. The mutant receptor (CAm5) was subjected to detailed pharmacological
      analysis. All of the antagonists tested (atropine, quinuclidinyl benzilate, N
      methyl scopolamine, 4-diphenylacetoxy-N-methylpiperidine and pirenzepine) fully
      suppressed both the constitutive and agonist-induced activities of CAm5 revealing
      that these ligands are negative antagonists (inverse agonists). The potency of
      these ligands was similar at the mutant and wild-type receptors, suggesting that
      the antagonist binding site of this receptor is unchanged. The mutant had
      increased sensitivity to the agonists carbachol, arecoline, and McN-A-343 as
      measured both by functional response and by radioligand binding. These effects
      are explained and predicted by a model in which the primary effect of the
      mutations is to alter a spontaneous equilibrium existing between the active and
      inactive states of the receptor.

PMID- 8531093
TI  - Prostaglandins mediate the stimulatory effects of endothelin-1 on cAMP
      accumulation and inositol-1,4,5-trisphosphate production and contraction in cat
      iris sphincter.
AB  - We previously reported that in the iris sphincter smooth muscle, endothelin-1 (ET
      1) activates both adenylyl cyclase and the phosphoinositide cascade and that the
      changes in the levels of cAMP and inositol-1,4,5-trisphosphate (IP3) produced are
      species specific. In the present study, we examined the mechanism of the ET-1
      effects in cat iris sphincter. In general, we found that ET-1 (0.1 microM)
      increased prostaglandin E2 (PGE2) release by 156%, cAMP accumulation by 310%, IP3
      production by 88% and induced contraction; that PGE2 increased cAMP accumulation,
      IP3 production and contraction; and that the effects of ET-1 are inhibited by
      indomethacin (Indo), suggesting that arachidonic acid metabolites may mediate the
      responses to the peptide. Kinetic studies revealed the following: (1) The effect
      of ET-1 on cAMP accumulation is rapid (within 30 sec), dose dependent (EC50 = 5.8
      nM) and completely abolished by Indo (Ki = 0.16 microM), a cyclooxygenase
      inhibitor, but not by nordihydroguairetic acid, a lipoxygenase inhibitor,
      implying the involvement of PGs. (2) ET-1 dose-dependently evoked PGe2 release
      (EC50 = 1.8 nM), IP3 production (EC50 = 4.5 nM) and contraction (EC50 = 5 nM) and
      that all of these responses were inhibited by Indo. (3) PGE2 increased cAMP
      accumulation in a dose-dependent manner with an EC50 of 1.5 x 10(-7) M, and PGD2
      and PGF2 alpha had little effect on the cyclic nucleotide. (4) PGE2 (1 microM),
      increased IP3 production by 55% and induced muscle contraction in a dose
      dependent manner (EC50 = 40 nM). We conclude from these data that in cat iris
      sphincter PGs may mediate ET-1-induced cAMP accumulation, IP3 production and
      smooth muscle contraction.

PMID- 8531094
TI  - Stimulation of opioid mu-receptors potentiates beta adrenoceptor-mediated
      relaxation of canine airway smooth muscle.
AB  - To elucidate the effect of an opioid on airway smooth muscle relaxant responses
      and its mechanism of action, we studied canine bronchial segments under isometric
      conditions in vitro. Addition of the opioid mu-receptor-specific agonist DAMGO
      (10(-5) M) or Tyr-D-Arg-phe-Lys-NH2 (10(-5) M) did not alter the resting tension
      or the contractile responses to Ach but augmented the relaxation induced by
      isoproterenol: the concentrations of isoproterenol required to produce a half
      maximal effect were decreased from 1.9 +/- 0.6 x 10(-6) to 3.1 +/- 1.0 x 10(-7) M
      (P < .01) by DAMGO and from 2.1 +/- 0.4 x 10(-6) M to 4.3 +/- 0.7 x 10(-7) M (P <
      .01), by Tyr-D-Arg-phe-Lys-NH2. This effect of DAMGO was concentration-dependent
      and was abolished by naloxone or Cys2, Tyr3, Orn5, Pen7-amide, a mu-receptor
      antagonist. DAMGO likewise caused a leftward displacement of concentration
      response curves for forskolin but was without effect on those for 3-isobutyl-3
      methylxanthine and 8-bromo-cAMP. Also, DAMGO did not affect the relaxant
      responses to verapamil, nitroprusside or 8-bromo-cGMP. Incubation of bronchial
      smooth muscle with DAMGO (10(-5) M) potentiated the intracellular accumulation of
      cAMP induced by isoproterenol (10(-6) M) from 258 +/- 22 pmol/g tissue wt. to 420
      +/- 27 pmol/g tissue wt. (P < .01), an effect that was abolished by naloxone.
      These results suggest that stimulation of opioid mu-receptors specifically
      augments beta adrenoceptor-mediated bronchodilation probably by acting at the
      site proximal to adenylate cyclase in the cAMP-dependent pathway.

PMID- 8531095
TI  - Cholecystokinin octapeptide reverses mu-opioid-receptor-mediated inhibition of
      calcium current in rat dorsal root ganglion neurons.
AB  - Cholecystokinin octapeptide (CCK-8) is reported to antagonize the analgesic
      effect produced by mu- and kappa- but not delta-opioid agonist in spinal cord.
      However, the mechanisms of interaction remain obscure. In the present study,
      whole-cell patch-clamp recording was performed on acutely isolated rat dorsal
      root ganglion (DRG) neurons to evaluate the effects of the highly specific mu
      opioid agonist ohmefentanyl and the delta-opioid agonist DPDPE on voltage-gated
      calcium channels and the possible interaction between CCK-8 receptor and mu- or
      delta-opioid receptor. The results indicated that ohmefentanyl, but not DPDPE,
      can suppress the voltage-gated calcium currents elicited in DRG neurons, an
      effect readily reversed by naloxone or by the antiopioid peptide CCK-8. The
      effect of CCK-8 can in turn be abolished by the CCK-B receptor antagonist
      L365,260. CCK-8 used by itself has no enhancing effect, but rather a depressant
      effect, on calcium currents. However, used simultaneously with ohmefentanyl, CCK
      8 shows a clear-cut reversal of depression of the mu-opioid. We conclude that the
      depressant effect produced by mu-opioid on voltage-gated calcium current in DRG
      neurons can be antagonized by CCK-8 through CCK-B receptor located in the same
      neuron. The delta-opioid DPDPE has no direct effect on the voltage-gated calcium
      current in DRG neurons.

PMID- 8531096
TI  - Pharmacological role and degradation processes of neuromedin N in the
      gastrointestinal tract: an in vitro and in vivo study.
AB  - Neuromedin N (NN) induced a concentration-dependent contraction (ED50 = 2.3 +/-
      0.2 microM) of the isolated longitudinal smooth muscle from guinea pig ileum.
      This effect was drastically enhanced (ED50 = 0.06 microM) by the aminopeptidases
      M and B inhibitor bestatin (10 microM), which elicited a 40-fold increase in NN
      potency. HPLC analysis indicated that the main NN catabolite generated by
      membranes from guinea pig longitudinal smooth muscle homogenate corresponded to
      des-Lys1-NN, which results from removal of the N-terminal lysyl residue of NN.
      The fact that the formation of des-Lys1-NN was fully prevented by bestatin (10
      microM) further supports the involvement of aminopeptidases in NN degradation. We
      examined the catabolic fate of NN in vivo in the vascularly perfused dog ileum.
      Bolus administration or continuous infusion of the peptide led to rapid
      disappearance of NN. This was prevented by prior treatment of ileal segments with
      bestatin (10 microM) but not with arphamenine B (0.5 microM), which indicated
      that aminopeptidase M but not aminopeptidase B participated in NN proteolysis in
      vivo. We showed that 1 and 10 nmol NN trigger the release of 28 +/- 5 and 59 +/-
      1 pmol, respectively, of endogenous vasoactive intestinal polypeptide-like
      immunoreactivity after infusion in the vascularly perfused dog ileum. This
      release was virtually doubled by prior treatment with 10 microM bestatin but not
      with 0.5 microM arphamenine B. Altogether, our data indicate that aminopeptidase
      M is largely responsible for NN degradation in vitro and in vivo in the
      gastrointestinal tract and could be considered the physiological inactivator of
      NN in the gut.

PMID- 8531097
TI  - Methylmercury acts at multiple sites to block hippocampal synaptic transmission.
AB  - To explore the mechanisms by which methylmercury (MeHg) blocks central synaptic
      transmission, intracellular recordings of action potentials and resting membrane
      potentials were made in CA1 neurons of rat hippocampal slices. At 4 to 100
      microM, MeHg blocked action potentials in a concentration- and time-dependent
      manner. MeHg also depolarized Ca1 neuronal membranes. However, this effect
      occurred more slowly than block of action potentials because the resting membrane
      potentials remained unchanged when threshold stimulation-evoked action potentials
      were blocked. Thus, MeHg may initially alter the threshold level of neuronal
      membrane excitability and subsequently depolarize the membrane leading to block
      of synaptic transmission. To identify potential sites of action of MeHg, effects
      of MeHg on the responses of CA1 neurons to orthodromic stimulation of Schaffer
      collaterals, antidromic stimulation of the alveus, direct injection of current at
      cell soma and iontophoretic application of glutamate were compared. At 20 and 100
      microM, MeHg blocked action potentials evoked by stimulation of Schaffer
      collaterals and by current injection at the cell soma at similar times. In
      contrast, action potentials evoked by stimulation of the alveus were blocked more
      rapidly by 100 microM MeHg than were action potentials evoked by current
      injection at CA1 neuronal soma. MeHg also blocked the responses of CA1 neurons to
      iontophoresis of glutamate, but time to block of these responses was slower than
      block of the corresponding orthodromically-evoked responses by stimulation of
      Schaffer collaterals. Compared to excitatory postsynaptic potentials, inhibitory
      postsynaptic potentials appeared to be more sensitive to MeHg, because block of
      inhibitory postsynaptic potentials occurred before block of excitatory
      postsynaptic potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531098
TI  - L(+)- and D(-)-lactate modulate rat renal tubular accumulation of amantadine in
      the presence and absence of bicarbonate.
AB  - The effect of L(+)-, D(-)- and racemic (DL)-lactate on the energy-dependent renal
      uptake of the achiral organic cation amantadine was determined with purified
      proximal and distal cortical tubule fragments isolated from rat kidneys. Kinetic
      parameters for uptake of amantadine were measured, under constant pH, in
      bicarbonate buffer (Krebs-Henseleit [KHS]), and in lactate buffers (5 mM) with
      different proportions of the enantiomers. Km for amantadine uptake increased in
      all lactate buffers compared with KHS for both proximal and distal tubules. Km
      for uptake in DL-lactate was similar to that in D(-)-lactate for proximal tubules
      and to L(+)-lactate in distal tubules, but Km in L(+)-lactate was higher than in
      D(-)-lactate for both tubules. Maximal transport capacity (Vmax) in DL-lactate
      and mixtures of enantiomers were similar to KHS but higher than in pure L(+)- and
      D(-)-lactate. In KHS, lactate inhibited energy-dependent amantadine uptake in a
      biphasic manner. Graded competitive inhibition of amantadine uptake was observed
      between 1 and 15 mM lactate for both proximal and distal tubules. This first
      phase (1-15 mM) inhibited 60% of amantadine uptake. The second phase (15-20 mM
      lactate) showed a much steeper slope and inhibited the remaining amantadine
      uptake. There were no differences in inhibitory potencies of the lactate
      enantiomers for either proximal tubules or distal tubules amantadine tubule
      uptake. Our present studies suggest that L(+)- and D(-)-lactate modulate
      amantadine transport by interacting directly with the bicarbonate-dependent
      transport mechanism(s).

PMID- 8531099
TI  - Hemodynamic effects of acute and chronic treatment with aladotril, a mixed
      inhibitor of neutral endopeptidase and angiotensin I-converting enzyme, in
      conscious rats with myocardial infarction.
AB  - The aim of the present study was to determine, in rats with myocardial
      infarction, the systemic and cardiac hemodynamic effects of aladotrilat and of
      its prodrug, aladotril, both of which display inhibitory activity toward both
      neutral endopeptidase (NEP, EC. 3.4.24.11) and angiotensin I-converting enzyme
      (ACE). The effects of acute intravenous injection of aladotrilat (30 mg/kg bolus
      injection plus 30 mg/kg/hr infusion) were measured for 1 hr in conscious
      infarcted rats and compared with the effects of SQ 28,603, a selective NEP
      inhibitor (30 mg/kg bolus injection plus 30 mg/kg/hr infusion), and captopril, a
      selective ACE inhibitor (10 mg/kg bolus injection plus 10 mg/kg/hr infusion).
      Unlike SQ 28,603, aladotrilat and captopril produced a slight fall in mean
      arterial blood pressure. The three treatments had no significant effect on heart
      rate and rate of increase of left ventricular pressure (LV + dP/dt) but caused
      significant decreases in left ventricular end-diastolic pressure (LVEDP). The
      effect of aladotrilat on decreasing LVEDP was faster than those of captopril or
      SQ 28,603. In chronic experiments, groups of rats received orally, twice daily,
      captopril (10 mg/kg), aladotril (100 mg/kg) or vehicle. Treatments were started
      18 to 20 hr after coronary artery ligation and continued for 4 weeks. Hemodynamic
      parameters and cardiac hypertrophy were measured at the end of therapy. Unlike
      aladotril, captopril treatment resulted in significant decreases in mean arterial
      blood pressure and left ventricular systolic pressure (approximately 15 mm Hg)
      and produced renal vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531100
TI  - Characterization of 5-lipoxygenase inhibitors in biochemical and functional in
      vivo assays.
AB  - Several potent and selective inhibitors of 5-lipoxygenase (5-LO) have been
      recently developed with excellent activity in certain in vivo assays of
      leukotriene production. The efficacy of three such inhibitors that have been in
      clinical trials (zileuton, A-78773 and ZD2138) were evaluated in: 1) ex vivo
      whole blood assay, 2) dermal Arthus reaction, and 3) functional airway response.
      In addition, a model of eicosanoid production in rat lung was developed that
      provides a simple assay for evaluation of the biochemical efficacy of 5-LO
      inhibitors in the lung. Bronchoalveolar lavage of rat lung with calcium ionophore
      A23187 resulted in rapid and robust production of PGE2, 6-keto-PGF1 alpha,
      thromboxane (TxB2), and leukotriene B4 (LTB4). Supplementation of lavage fluid
      with archidonic acid markedly augmented production of all eicosanoids except
      LTB4. All three inhibitors were potent and selective blockers of LTB4 production
      in the ex vivo whole blood assay and in the dermal Arthus reaction. In contrast,
      higher doses of inhibitor were needed to block LTB4 production in the rat lung
      lavage model than were needed to block ex vivo whole blood LTB4 production when
      both end points were measured in the same animal. Similarly, zileuton and A-78733
      were less effective in suppressing the functional airway response to antigen in
      sensitized guinea pigs, whereas both inhibitors were effective in suppressing
      LTB4 production in the ex vivo whole blood assay. These results demonstrate that
      different 5-LO inhibitors have markedly distinct efficacy for inhibition of
      leukotriene production, depending on the animal model.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8531101
TI  - Regulation of morphine antiallodynic efficacy by cholecystokinin in a model of
      neuropathic pain in rats.
AB  - Neuropathic pains have often been classified as opioid-resistant. Here, spinal
      (intrathecal) actions of morphine and nonmorphine opioids have been studied in a
      nerve ligation model of neuropathic pain in rats. Mechanical allodynia was
      evaluated using von Frey filaments. Nerve-injured animals exhibited allodynia
      that was stable for up to 6 weeks after the surgery. Morphine did not alter
      allodynia at doses up to 300 nmol (100 micrograms). In contrast, [D-Ala2, NMPhe4,
      Gly-ol]enkephalin (DAMGO), a high-efficacy mu opioid agonist, produced a
      significant, dose-related antiallodynic action. [D-Ala2, Glu4]deltorphin (delta
      agonist) produced a significant antiallodynic effect only at 300 nmol, reaching
      approximately 70% of the maximum. Coadministration of morphine with a dose of [D
      Ala2, Glu4]deltorphin, which was inactive alone, produced a significant and long
      lasting antiallodynic action that was antagonized by NTI (delta receptor
      antagonist); NTI alone had no effect. Although blockade of cholecystokinin-B
      (CCKB) receptors with L365,260 did not produce effects alone, a significant
      antiallodynic action was observed when coadministered with morphine; this
      elevation of nociceptive threshold was abolished by NTI. The finding that DAMGO,
      but not very large doses of morphine, produced antiallodynic actions suggests
      that the ability of mu opioids to alleviate the allodynia is related, in part, to
      efficacy at postsynaptic mu receptors. At an inactive dose, a delta agonist or a
      CCKB antagonist enhanced morphine antiallodynic efficacy in an NTI-sensitive
      fashion. CCKB receptor blockade may enhance endogenous enkephalin actions,
      resulting in enhancement of morphine efficacy through a mu-delta receptor
      interaction.

PMID- 8531102
TI  - Antinociceptive effects of cocaine/opioid combinations in rhesus monkeys.
AB  - This study characterized the antinociceptive effects of cocaine alone and in
      combination with mu, delta, and kappa opioids in rhesus monkeys. The shaved tails
      of four rhesus monkeys were exposed to warm water (42, 46, 50, 54, and 58 degrees
      C), and tail withdrawal latencies (20 sec maximum) from each temperature were
      determined. The temperature that produced a tail withdrawal latency of 10 sec
      (T10) was interpolated, and drug-induced changes in the T10 value (delta T10)
      were calculated. Dose-dependent increases in delta T10 were produced by cocaine
      (0.032-1.8 mg/kg), the high efficacy mu agonist fentanyl (0.001-0.1 mg/kg), the
      intermediate efficacy mu agonist morphine (0.1-18 mg/kg), the low efficacy mu
      agonist nalbuphine (1-32 mg/kg), and the kappa agonist U69,593 (0.0032-0.1
      mg/kg). The delta agonist BW373U86 (0.56 mg/kg) produced no effect. Relative
      maximum effects, determined from the maximum delta T10 values produced by each
      drug, were fentanyl > or = (5,7,8 beta)-N-methyl-N[2-(1-pyrrolidinyl)1
      oxaspiro[4,5]dec-8- yl]benzeneacetamide > morphine > nalbuphine > or = cocaine >
      BW373U86. When individual doses of cocaine (0.1-1.8 mg/kg) and morphine (0.32
      10.0 mg/kg) were combined, cocaine produced a dose-dependent increase in the
      effects of each dose of morphine, and the antinociceptive effects of most
      cocaine/morphine combinations were significantly greater than the antinociceptive
      effects of either cocaine or morphine alone. Cocaine (1.8 mg/kg) was also
      combined with nalbuphine (1.0, 10 mg/kg), fentanyl (0.001, 0.032 mg/kg), BW373U86
      (0.56 mg/kg) and U69,593 (0.0032-0.056 mg/kg). Cocaine/nalbuphine combinations
      produced effects markedly greater than either drug alone.

PMID- 8531103
TI  - Neurochemical and functional characterization of the preferentially selective
      dopamine D3 agonist PD 128907.
AB  - The present study determined the biochemical and pharmacological effects of PD
      128907 [R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H- [1]benzopyrano[4,3-b]
      1,4-oxazin-9-ol], a dopamine (DA) receptor agonist that shows a preference for
      the human D3 receptor. In transfected Chinese hamster ovary cells (CHO K1), PD
      128907 displaced [3H]spiperone in a biphasic fashion which fit best to a two-site
      model, generating Ki values of 20 and 6964 nM for the high- and low-affinity
      sites for the D2L receptors and 1.43 and 413 nM for the corresponding sites for
      the D3 receptors. Addition of sodium and the GTP analog Gpp(NH)p to both the D2L
      and D3 caused a modest reduction in the affinity of the compound suggestive of an
      agonist type action. In agonist binding ([3H]N-0437), PD 128907 exhibited an 18
      fold selectivity for D3 versus D2L, a selectivity similar to that found with
      antagonist binding to the high-affinity sites. PD 128907 exhibited only weak
      affinity for D4.2 receptors (Ki = 169 nM). No significant affinity for a variety
      of other receptors was observed. PD 128907 stimulated cell division (measured by
      [3H]thymidine uptake) in CHO p-5 cells transfected with either D2L or D3
      receptors exhibiting about a 6.3-fold greater potency in activating D3 as
      compared to D2L receptors. In vivo the compound was active in reducing DA
      synthesis both in normal and gamma-butyrolactone (GBL) treated rats; in the GBL
      model, the decrease was greater in the higher D3-expressing mesolimbic region as
      compared with striatum which has a lower expression of D3 receptors. PD 128907
      decreased DA release (as measured by brain microdialysis) both in rat striatum,
      nucleus accumbens and medial frontal cortex, as well as in monkey putamen.
      Behaviorally PD 128907 decreased spontaneous locomotor activity (LMA) in rats at
      low doses, whereas at higher doses stimulatory effects were observed. PD 128907
      at high doses reversed the reserpine-induced decrease in LMA and induced
      stereotypy in combination with the D1 agonist SKF 38393 indicating postsynaptic
      DA agonist actions. It is unclear which of the subtypes of DA receptors might be
      mediating the pharmacological effects of PD 128907. However, the present findings
      indicating that PD 128907 shows a preference for DA D3 over D2L and D4.2
      receptors indicates that its action at low doses may be due to interaction with
      D3 receptors and at higher doses, with both D2 and D3 receptors.

PMID- 8531104
TI  - The reinforcing effects of dopamine D1 receptor agonists in rhesus monkeys.
AB  - Central dopaminergic systems have been implicated in the reinforcing effects of a
      number of stimuli, including drugs of abuse; however, the role of dopamine D1
      receptors remains controversial. The present study evaluated the reinforcing
      effects of six reportedly selective D1 agonists of differing intrinsic
      efficacies. Rhesus monkeys with chronic intravenous catheters lever pressed on a
      fixed-ratio 10 schedule maintained by a base-line cocaine dose of 0.03 mg/kg/inj
      in daily 1-hr sessions. Periodically, D1 agonists were substituted for the
      cocaine base-line. All monkeys (n = 4) self-administered the high-efficacy D1
      agonists SKF 81297, SKF 82958 and R(+) 6-Br-APB at rates above those maintained
      by vehicle; therefore, each of these compounds functioned as a positive
      reinforcer (maxima: SKF 81297: 55-172 inj/hr, 0.01 mg/kg/inj; R(+) 6-Br-APB:103
      165 inj/hr, 0.001 mg/kg/inj; SKF 82958: 110-149 inj/hr, 0.01 mg/kg/inj). In
      contrast, no monkeys self-administered the lower-efficacy D1 agonists SKF 38393
      (N = 4), SKF 77434 (N = 4) or the S(-) enantiomer of 6-Br-APB (N = 2).
      Additionally, two stimulant-naive monkeys acquired self-administration of SKF
      81297. The finding that selective D1 receptor agonists can function as positive
      reinforcers implicates D1 receptors in the reinforcing effects of psychomotor
      stimulants and of other drugs that stimulate D1 receptors.

PMID- 8531105
TI  - Short-term drug effects on the signal-averaged electrocardiogram in healthy men:
      assessment of intra- and interindividual variability of spectral temporal mapping
      and time-domain analysis.
AB  - The effect of cardiovascular drugs on the results of the signal-averaged
      electrocardiogram (SA-ECG) was studied in healthy young subjects. Cardiovascular
      drugs may confound the analysis of SA-ECG, but the effect of drugs on time-domain
      analysis and on spectral temporal mapping (STM) in healthy subjects has not been
      investigated under standardized conditions. Also, the reproducibility of the
      various spectral area measurements of STM has not been assessed simultaneously.
      Short-term drug effects on the SA-ECG were studied in 20 healthy young men (age
      23.5 +/- 2.5 years) in an observer-blinded, crossover design on separate days.
      Each subject was randomly assigned to four drugs. The SA-ECG was recorded at
      baseline and during i.v. administration of stepwise increased doses of adenosine,
      atropine, isoproterenol, lidocaine, norepinephrine, propranolol, verapamil and
      placebo. Low amplitude signal duration was significantly and dose-dependently
      shortened by isoproterenol, whereas no consistent effect on the filtered QRS
      duration or on the root mean square voltage in the terminal 40 ms of time-domain
      analysis was noted for any of the other drugs. Only lidocaine significantly and
      dose-dependently decreased the parameters of STM at QRS offset and +20 ms, even
      though short-term reproducibility and day-to-day reproducibility of spectral area
      measurements were low. Interpretation of "normal" results from SA-ECG is not
      relevantly influenced by the studied drugs at clinical doses. STM may prove a
      useful technique for detection of the actions of sodium channel-blocking drugs.
      Reproducibility of STM measurements is substantially lower than that of time
      domain parameters.

PMID- 8531106
TI  - BIII 277 CL is a potent and specific ion-channel blocker of the NMDA receptor
      channel complex.
AB  - We determined the ability of a new benzomorphan derivative [2R-[2 alpha, 3(R*),6
      alpha]]-1,2,3,4,5,6-hexahydro-3-(2-methoxypropyl)- 6,11,11-trimethyl-2,6-methano
      3-benzazocin-9-ol hydrochloride (BIII 277 CL) to inhibit the N-methyl-D-aspartic
      acid (NMDA) receptor-channel complex in vitro and in vivo. BIII 277 CL potently
      displaced [3H]MK-801 binding from the NMDA receptor-channel complex in
      synaptosomal membrane preparations from rat brain cortex (Ki = 4.49 nmol/l). It
      was much less effective at displacing [3H]dihydromorphine, [3H]naloxone and
      [3H]ditolyguanidine binding in similar membrane preparations: the Ki values were
      3323, 8031 and 1017 nmol/l, respectively. BIII 277 CL did not exhibit any marked
      affinities for a variety of other central neurotransmitter receptors. BIII 277 CL
      antagonized NMDA-induced [3H]noradrenaline release (EC50 = 1.7 mumol/l) and NMDA
      induced inhibition of protein synthesis in rat hippocampal slices (EC50 = 3.0
      mumol/l). In mice, BIII 277 CL prevented NMDA-induced lethality (ID50 = 0.54
      mg/kg s.c.) and, as expected, also caused disturbances in motor coordination in
      the same dose range (ED50 = 0.47 mg/kg s.c.). The duration of BIII 277 CL was
      much shorter than than of (+)MK-801 in both tests. Finally, BIII 277 CL (0.3
      mg/kg s.c. 5 times over 24 h) reduced the cortical infarct area in mice that had
      been subjected previously to focal cerebral ischemia by unilateral occlusion of
      the middle cerebral artery. In summary, these results indicate that BIII 277 CL
      is a potent and specific ion-channel blocker of the NMDA receptor-channel complex
      which could be used for the treatment of acute thromboembolic stroke in humans.

PMID- 8531107
TI  - U-89843A is a novel allosteric modulator of gamma-aminobutyric acidA receptors.
AB  - A group of pyrrolopyrimidine derivatives were examined for their interaction with
      rat recombinant gamma-aminobutyric acid (GABA)A receptors using the whole cell
      patch clamp and equilibrium binding techniques. In the alpha 1 beta 2 gamma 2
      subtype of GABAA receptors expressed in human embryonic kidney cells, a prototype
      pyrrolopyrimidine, U-89843A (7H-pyrrol[2,3-d]pyrimidine,6,7-methyl-2,4-di- 1
      pyrrolidinyl,hydrochloride), dose-dependently enhanced 5 microM GABA-induced Cl-
      currents with a maximal enhancement of 362 +/- 91%, a half-maximal concentration
      of 2 +/- 0.4 microM and a slope factor of 1.1 +/- 0.4. The drug also inhibited
      [35S]t-butylbicyclophosphorothionate binding in rat cerebrocortical membranes
      with a similar half-maximal inhibitory concentration. The enhancement of Cl-
      currents by U-89843A was insensitive to Ro 15-1788 (a benzodiazepine antagonist),
      was also observed in the alpha 3 beta 2 gamma 2 and alpha 6 beta 2 gamma 2
      subtypes (no selectivity to different alpha-isoforms unlike many
      benzodiazepines), but was absent in the receptor subtypes consisting of two
      subunits (alpha 1 beta 2, alpha 1 gamma 2 and beta 2 gamma 2). It has been known
      that neurosteroids and barbiturates are uniformly active in both the two subunit
      receptors, substituted pyrazinones are only active in the alpha 1 beta 2 subtype
      and loreclezole is active in the subtypes containing beta 2. We propose that U
      89843A interacts with an allosteric site on GABAA receptors distinct from the
      sites for benzodiazepines, barbiturates, neurosteroids, substituted pyrazinones
      or loreclezole.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531108
TI  - Stimulatory effect of leminoprazole on secretion and synthesis of mucus by rabbit
      gastric mucosal cells.
AB  - We examined whether leminoprazole (an acid pump inhibitor) enhances the secretion
      and synthesis of gastric mucus in vitro. Mucosal cells were prepared from male
      rabbit stomachs, and the amounts of secreted and synthesized mucus were
      determined by the [3H] glucosamine labeling method. Exposure of gastric mucosal
      cells to leminoprazole at 1 to 100 microM for 8 hr caused significant increases
      in the secretion and synthesis of mucus in a dose-related manner, but omeprazole
      was not effective. The stimulatory effects of leminoprazole on secretion and
      synthesis were observed 4 hr and 6 hr later, respectively. In contrast, both
      16,16-dimethyl prostaglandin E2 and nitroprusside, a nitric oxide (NO) generator,
      caused marked increases in mucus secretion and synthesis even after 2-hr
      incubation. The effects of leminoprazole on gastric mucus were strongly inhibited
      by NO synthase inhibitors such as NG-nitro-L-arginine methyl ester and NG
      monomethyl-L-arginine and by the NO scavenger oxyhemoglobin. However, neither
      indomethacin (an inhibitor of cyclooxygenase), aminoguanidine (an inhibitor of
      inducible nitric oxide synthase) nor cycloheximide (a protein synthesis
      inhibitor) could suppress its effects. These results suggest that leminoprazole
      stimulates the secretion and synthesis of gastric mucus after a lag period,
      probably through NO produced by constitutive NO synthase.

PMID- 8531109
TI  - Selective block of tetramethrin-modified sodium channels by (+/-)-alpha
      tocopherol (vitamin E).
AB  - Pyrethroids exert their hyperexcitatory effects by prolonging the open time of
      individual neuronal sodium channels. Occupational exposure to pyrethroids
      frequently leads to abnormal skin sensation or paresthesia. Vitamin E is known to
      reduce the cutaneous paresthesia. However, the mechanism of action has been
      totally unclear. Because the sodium channel is the major target site of
      pyrethroids, it is possible that vitamin E interferes with pyrethroid
      modification of the sodium channel. Patch clamp experiments were performed using
      rat dorsal root ganglion neurons and cerebellar Purkinje cells. (+/-)-alpha
      Tocopherol (vitamin E) selectively blocked the tetramethrin(type I pyrethroid)
      modified sodium channels in a dose-dependent, but voltage-independent manner
      without affecting normal sodium channels. The concentration-response curves for
      tetramethrin modification of the sodium channels were shifted in the direction of
      higher concentrations by (+/-)-alpha-tocopherol in a competitive manner. Elevated
      depolarizing after-potential or repetitive after-discharges caused by
      tetramethrin were effectively blocked by (+/-)-alpha-tocopherol. (+/-)-alpha
      Tocopherol did not reverse the tetramethrin-induced shift in the current-voltage
      curve for peak sodium current, but partially reversed the shift in the steady
      state sodium channel inactivation curve. Vitamin A and its metabolic derivative,
      retinoic acid, slightly reduced both normal and tetramethrin-modified sodium
      currents. The selective block of tetramethrin-modified sodium channels by (+/-)
      alpha-tocopherol is one of the important mechanisms underlying (+/-)-alpha
      tocopherol alleviation of paresthesia.

PMID- 8531110
TI  - Influence of the estrus cycle on the discrimination of apparent neuroactive
      steroid site subtypes on the gamma-aminobutyric acidA receptor complex in the
      rat.
AB  - Estrus cycle-related changes in gamma-aminobutyric acid (GABA)A receptor complex
      (GRC) sensitivity to modulation by reduced progesterone metabolites is suggestive
      of a possible mechanism for maintaining brain homeostasis in the presence of
      fluctuating levels of these neuroactive metabolites. In addition, certain
      endogenously occurring pregnanediols are selective for apparent neuroactive
      steroid site subtypes discriminated by the progesterone metabolite 3 alpha
      hydroxy-5 beta-pregnan-20-one (3 alpha,5 beta-P) on the GRC. Thus, it was of
      interest to evaluate the influence of gender and the estrus cycle on the ability
      of 3 alpha,5 beta-P and its 20-reduced analog 5 beta-pregnan-3 alpha,20 beta-diol
      to differentiate neuroactive steroid site subtypes. Neuroactive steroid
      modulation of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to the GRC
      in rats during estrus, diestrus and after ovariectomy (OVX) was measured in
      washed cortical P2 homogenates in the presence or absence of exogenous GABA.
      During diestrus, the inability of 5 beta-pregnan-3 alpha,20 beta-diol to
      allosterically modulate [35S]TBPS binding in the absence of GABA coincides with
      the inability of 3 alpha,5 beta-P to modulate [35S]TBPS binding with high
      potency. In contrast, the addition of GABA to the assay produced high potency
      inhibition of [35S]TBPS binding by each steroid. Remarkably, although findings in
      diestrus and OVX homogenates were no different from those observed in males, the
      proportions and IC50 values of the two sites discriminated by 3 alpha,5 beta-P in
      [35S]TBPS binding assays during the estrus phase were significantly different
      from male, OVX and diestrus rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531111
TI  - The "calcium antagonist" TMB-8 [3,4,5-trimethoxybenzoic acid 8
      (diethylamino)octyl ester] is a potent, non-competitive, functional antagonist at
      diverse nicotinic acetylcholine receptor subtypes.
AB  - [3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester] (TMB-8) has seen wide
      use as an "intracellular Ca2+ antagonist." However, this study shows that TMB-8
      acts as a noncompetitive, functional antagonist at diverse nicotinic
      acetylcholine receptor (nAChR) subtypes with potencies that exceed those for
      other reported effects of TMB-8, including inhibition of intracellular Ca2+
      mobilization. TMB-8 is a potent inhibitor (IC50 approximately 400 nM) of agonist
      stimulated ion flux mediated by functional human muscle nAChR or ganglionic alpha
      3 beta 4-nAChR subtypes expressed by TE671/RD or SH-SY5Y cells. TMB-8 is also a
      potent inhibitor (IC50 approximately 500 nM) of a functional, central nervous
      system nAChR subtype that mediates nicotinic agonist-stimulated [3H]dopamine
      release from rat brain synaptosomes. TMB-8 is much less potent (IC50
      approximately 30-200 microM) as an inhibitor of high-affinity 3H-labeled
      acetylcholine or 125I-labeled alpha-bungarotoxin binding to human muscle nAChR,
      ganglionic alpha 3 beta 4-nAChR, or ganglionic alpha 7-nAChR subtypes. Moreover,
      functional inhibition by TMB-8 of muscle-type nAChR is due to a reduction in
      agonist efficacy, but not potency, and is proportionately stronger with
      increasing agonist concentration, thereby suggesting that TMB-8 acts as a
      noncompetitive inhibitor. Similar effects are observed for local anesthetics such
      as tetracaine and procaine (functional IC50 values of approximately 5 and
      approximately 50 microM, respectively), although TMB-8 is the most potent of
      these agents. Studies with TMB-8 or BAPTA [1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid] analogues indicate that the amino group of TMB-8 is
      essential and that Ca2+ chelation is not required for inhibition of nAChR
      function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531112
TI  - Intestinal absorption of calcium in vivo is dependent on endogenous nitric oxide.
AB  - This study examines the role of nitric oxide (NO) in the regulation of calcium
      absorption in the small intestine. Calcium absorption was quantified by measuring
      45Ca++ transport from lumen to blood in an intestinal segment (duodenum and 20 cm
      of the proximal jejunum) perfused by both intraluminal and vascular routes in
      anesthetized rats. When administered i.v. as bolus injections, NG-nitro-L
      arginine methyl ester (L-NAME, 10 mg.kg-1), an inhibitor of NO biosynthesis,
      decreased calcium absorption with a concomitant increase in blood pressure and a
      decrease in mesenteric blood flow. Conversely, the nitrovasodilators 3
      morpholinosydnonimine (2 mg.kg-1) and S-nitroso-N-acetylpenicillamine (10
      micrograms.kg-1), which generate NO spontaneously, both increased calcium
      absorption with no change in mesenteric blood flow. When infused i.v., L-NAME (3
      mg.hr-1.kg-1 for 40 min) induced a decrease in calcium absorption that was
      reversed by the NO donor sodium nitroprusside (1.5 mg.hr-1.kg-1 when infused for
      the last 20 min of the 40-min L-NAME infusion). Sodium nitroprusside infusion
      (1.5 mg.hr-1.kg-1) caused an increase in calcium absorption that was not reversed
      by L-NAME (3 and 30 mg.hr-1.kg-1). The present findings suggest that NO is
      involved in basal calcium absorption in rat small intestine in vivo.

PMID- 8531113
TI  - Comparison between the effects of a novel Ca++ sensitizer and a phosphodiesterase
      inhibitor on stunned myocardium.
AB  - Inotropic agents are used widely for pharmacological bridging of the failing
      heart either until recovery after surgical intervention or until transplantation.
      EMD 57033 is a novel specific Ca++ sensitizing agent with purportedly minor
      phosphodiesterase (PDE) III-inhibiting properties. It acts as an inotropic agent
      without raising intracellular Ca++ levels. In turn, the PDE III-inhibitor
      enoximone has been used for several years to treat low cardiac output syndrome.
      However, little is known about its effects on postischemic reperfused (stunned)
      myocardium. We investigated the effects of EMD 57033 (EMD; 30 microM) and
      enoximone (E20 micrograms/ml) on stunned myocardium. The experiments were
      performed on 16 isolated rabbit hearts perfused with an erythrocyte suspension
      (hematocrit = 30%; [Ca++] = 2.5 mM). Hearts were reperfused after a 20 min no
      flow ischemia. Measurements were performed at control, 30 min after the onset of
      reperfusion, and after administration of one of the drugs. Both agents
      significantly improved the depressed systolic function [left ventricular pressure
      (LVP)max from 61 +/- 12 to 93 +/- 18 mmHg, and its derived pressure (dP/dt)max
      from 860 +/- 220 to 1340 +/- 300 mmHg/s and LVPmax from 78 +/- 9 to 83 +/- 15
      mmHg, and its derivative dP/dtmax from 1040 +/- 230 to 1385 +/- 300 mmHg/s,
      respectively] and early relaxation (dP/dtmin from 810 +/- 250 to 1260 +/- 345
      mmHg/s and from 1000 +/- 200 to 1135 +/- 295 mmHg/s, respectively) that occurred
      during postischemic reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531114
TI  - Effects of chronic pentobarbital treatment on the GABAA receptor complex in
      mammalian cortical neurons.
AB  - In this study we examined the binding characteristics of the gamma-aminobutyric
      acid (GABAA) receptor complex after chronic pentobarbital sodium treatment in
      cultured mammalian cortical neurons. Chronic pentobarbital sodium treatment (200
      microM, 5 days) did not alter the basal binding of ligands like
      [3H]flunitrazepam, [3H]ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5
      alpha][1,4]-BZ-3-carboxylate and [3H]ethyl-8-azido-5,6-dihydro- 5-methyl-6-oxo-4H
      imidazo [1,5 alpha][1,4]BZ-3-carboxylate that bind to the benzodiazepine (BZ)
      recognition site of the GABAA receptor complex. Similarly, chronic pentobarbital
      sodium treatment did not alter the basal binding of [3H]GABA and t
      butylbicyclophosphoro[35S]thionate. However, chronic pentobarbital sodium
      treatment produced uncoupling between GABA, barbiturate and neurosteroid sites
      with the BZ site. The efficacy (Emax) values of GABA, pentobarbital and
      neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one, on [3H]flunitrazepam binding
      were significantly decreased, whereas their potency (EC50) values were not
      altered after chronic pentobarbital sodium treatment. Taken together, these
      results suggest that chronic pentobarbital sodium treatment produces heterologous
      uncoupling of the GABA-BZ receptor ionophore complex.

PMID- 8531115
TI  - Tenidap, an anti-inflammatory agent, discharges intracellular Ca++ store and
      inhibits Ca++ influx in cultured human gingival fibroblasts.
AB  - The effect of tenidap, (+/-)-5-chloro-2,3-dihydro-3-(hydroxy-2- thienylmethylene)
      2-oxo-1H-indole-1-carboxamide, a new anti-inflammatory agent, was investigated on
      intracellular free Ca++ concentration ([Ca++]i) responses evoked by bradykinin
      and thapsigargin in gingival fibroblasts. Tenidap itself stimulated [Ca++]i
      response in a dose-dependent manner in the absence of extracellular Ca++. The
      pretreatment with tenidap inhibited [Ca++]i responses evoked by 5 nM bradykinin
      and 1 microM thapsigargin in a dose-dependent manner. This indicates that tenidap
      discharges intracellular Ca++ store, resulting in a depletion of intracellular
      Ca++ store. Tenidap partially depressed Ca++ influx across plasma membrane by 1
      to 2 min pretreatment and almost completely by more than 5 min pretreatment.
      Thus, tenidap appears to be a valuable agent that functions on inhibition of Ca++
      influx in nonexcitable cells, which is rare at the present time.

PMID- 8531116
TI  - Differential effects of 2,4-dithiobiuret on the synthesis and release of
      acetylcholine and dopamine from rat pheochromocytoma (PC12) cells.
AB  - Chronic administration of 2,4-dithiobiuret (DTB), causes delayed-onset
      neuromuscular weakness in rats. This effect results from inhibition of quantal
      release of acetylcholine (ACh) from motor nerve terminals. The effects of
      noncholinergic neurotransmission are unknown. The purpose of the present study
      was to examine the presynaptic mechanisms involved in DTB-induced inhibition of
      ACh release, particularly, the specificity of action of DTB for cholinergic
      secretion. Differentiated pheochromocytoma (PC12) cells were used to compare the
      effects of DTB on the content and release of ACh and dopamine (DA) using
      neurochemical techniques. At concentrations of 50 to 1000 microM, DTB had little
      or no effect on [3H]choline uptake or on the spontaneous release of endogenous or
      [3H]ACh, but caused a significant decrease in release of endogenous or [3H]ACh
      elicited by depolarization with elevated extracellular [K+]. DTB reduced evoked
      release of ACh without altering cellular levels of ACh or choline, suggesting
      that DTB acts directly on mechanisms involved in ACh release. These alterations
      occurred without prominent alterations in [Ca2+]i as measured by fluorescence
      microscopy of individual PC12 cells loaded with fura-2. Moreover, DTB did not
      affect the increase of [Ca2+]i of PC12 cells in response to KCl-induced
      depolarization. alpha-Latrotoxin-stimulated release of ACh was not inhibited by
      DTB. DTB-induced suppression of depolarization-evoked release of [3H]ACh was
      associated with an increased level of [3H]ACh in the vesicular pool although the
      cytosolic pool was unaffected. High concentrations of DTB also reduced
      depolarization-evoked release of DA and inhibited DA synthesis resulting in a
      decrease in the readily releasable pool of DA. These effects occurred at higher
      concentrations and after longer exposures to DTB than were necessary to alter ACh
      release. Inasmuch as DA synthesis in the PC12 cell has been shown to be modulated
      by ACh release, this effect on DA release may reflect a consequence of the
      diminished release of ACh. These results suggest that DTB alters the release of
      ACh by interrupting either the mobilization and/or release of the vesicular pool
      of ACh.

PMID- 8531117
TI  - The metabolic formation of reactive intermediates from clozapine, a drug
      associated with agranulocytosis in man.
AB  - Clozapine, a dibenzodiazepine antipsychotic, is associated with a 0.8% incidence
      of agranulocytosis. This clinically restrictive toxicity has been attributed to
      its chemically reactive metabolites. The generation of such metabolites--assessed
      via covalent binding and formation of thioether adducts--was investigated using
      human, rat and mouse liver microsomes and human neutrophils and bone marrow
      cells. In every instance, one major glutathione adduct of clozapine--C-6
      glutathionyl clozapine--was formed in the presence of added glutathione. Adduct
      formation by the neutrophils and myeloid cells was dependent on cell activation
      by phorbol myristate acetate. Small fractions of drug underwent covalent binding
      to microsomes (1-6.8%) and to protein coincubated with neutrophils (0.47%) and
      myeloid cells (0.21%). Clozapine did not deplete intracellular glutathione in
      activated neutrophils. Clozapine was also metabolized in vivo to glutathione
      conjugates in rats and mice, the conjugates eliminated in bile over a 3-hr period
      representing 38% and 33% of the dose, respectively. In addition to the principal
      clozapine adduct found in vitro, the C-8 glutathionyl derivative of
      deschloroclozapine was excreted by both species. It is concluded that clozapine
      undergoes bioactivation in several tissues and considerable bioactivation in
      vivo. The reactive metabolites generated by neutrophils and myeloid cells may
      play an important role in the metabolic causation of clozapine-induced
      agranuiocytosis.

PMID- 8531118
TI  - Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion
      that irreversibly binds to the cells.
AB  - Clozapine was oxidized to a reactive intermediate by HOCI, which is the major
      oxidant produced by activated neutrophils. A mass spectrum was obtained of this
      reactive intermediate by using a flow system in which the reactants were fed into
      a mixing chamber and the products flowed directly into a Sciex API III mass
      spectrometer. The intermediate was observed at m/z 325, which is 2 mass units
      less than the protonated molecular ion of the parent drug. This intermediate
      reacted with water to form several products with a m/z at 343. The same products
      were produced by the oxidation of clozapine by the combination of
      myeloperoxidase, hydrogen peroxide and chloride ion. The reactive intermediate
      was trapped by glutathione (GSH) and several conjugates were formed. Nuclear
      magnetic resonance spectra of the two major conjugates indicated GSH bound to the
      6 and 9 positions of the aromatic ring. These data provide further evidence for
      the formation of a formal nitrenium ion in which the positive charge is highly
      delocalized. Clozapine was also oxidized by activated neutrophils, and in the
      presence of GSH, the same GSH conjugates were formed. When therapeutic
      concentrations of radiolabeled clozapine were used, up to 7% of the drug became
      irreversibly bound to the neutrophils. Covalent binding was inhibited by about
      30% in the presence of 1 mM GSH but was almost abolished at 5 mM GSH. The
      putative nitrenium ion formed by activated leukocytes could be responsible for
      clozapine-induced agranulocytosis.

PMID- 8531119
TI  - Mouse strain differences in immunosuppression by opioids in vitro.
AB  - An in vitro assay was used to compare the effect of opioids on antibody
      production by splenocytes from C3HeB/FeJ, C57BL/6J, C57BL/6ByJ and B6C3F1/J mice
      immunized with sheep red blood cells (SRBC). Spleen cells were removed from mice
      that had been injected 2 wk prior with SRBC. These mice received no opioids in
      vivo. Dissociated spleen cells taken from each of the mouse strains were exposed
      to morphine with or without naloxone, or to U50,488H with or without
      norbinaltorphimine (nor-BNI), for 5 days in a Mishell-Dutton culture, with added
      SRBC as antigen. Immune responsiveness was assessed by the number of plaque
      forming cells (PFC) per culture. The results showed a profound difference in the
      effects of the opioids on the spleen cells of the four mouse strains. Spleen
      cells of C3HeB/FeJ mice were suppressed approximately 50% in the number of PFC
      both by morphine (10(-5) to 10(-8) M) and by U50,488H (10(-5) to 10(-11) M).
      Suppression was blocked by pretreatment with naloxone or norbinaltorphimine,
      respectively. In contrast, spleen cells taken from C57BL/6J mice were not
      suppressed by either opioid, at doses ranging from 10(-5) to 10(-11) M. Spleen
      cells of B6C3F1/J mice were suppressed by U50,488H, but not morphine. Cells of
      C57BL/6ByJ mice gave inconsistent results in experiments measuring suppression by
      morphine, and U50,488H. Overall, these studies confirm our previous work showing
      that opioids directly affect the function of cells of the immune system via
      classical opioid receptors. In addition, the results show that mouse strain is a
      major variable in evaluating the immunomodulatory effects of opioids.

PMID- 8531120
TI  - Potential risk of myopathy by HMG-CoA reductase inhibitors: a comparison of
      pravastatin and simvastatin effects on membrane electrical properties of rat
      skeletal muscle fibers.
AB  - To get insight into the potential risk of myopathy associated with therapy
      involving 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, we
      evaluated in vivo and in vitro the effects of a daily 2 to 3-month treatment with
      pravastatin (100 mg/kg) and with simvastatin (5, 10 and 50 mg/kg) on the
      electrical properties of rat skeletal muscle fibers. The electromyographic
      activity revealed no sign of myopathy during treatment with pravastatin and with
      simvastatin. At the end of the treatment, the passive and active membrane
      electrical parameters of the extensor digitorum longus muscles were measured in
      vitro by computerized two-intracellular-microelectrode technique. A dose
      dependent reduction of membrane chloride conductance was recorded in extensor
      digitorum longus fibers of simvastatin-treated groups, and at 50 mg/kg the
      reduction of chloride conductance was significant in 6 out of the 7 treated rats.
      By contrast, none of the pravastatin-treated rats showed significant alteration
      of chloride conductance. Consequently, the excitability parameters were modified
      by simvastatin but not by pravastatin treatment, whereas the resting membrane
      potential was not affected. An increase in potassium conductance, reduced by in
      vitro application of glybenclamide, was recorded in 30% of the simvastatin
      treated rats (50 mg/kg) and in only 15% of the pravastatin-treated rats. Our
      results suggest that the risk of myopathy is much higher with the lipophilic
      simvastatin than with the hydrophilic pravastatin and support the hypothesis that
      the muscle toxicity of HMG-CoA reductase inhibitors is due to an intracellular
      action mediated by the inhibition of muscle cholesterol synthesis.

PMID- 8531121
TI  - Thromboxane synthase inhibitors suppress more effectively the aggregation of
      thromboxane receptor-desensitized than that of normal platelets: role of
      adenylylcyclase up-regulation.
AB  - Exposure of human platelets to U46619, a thromboxane (Tx) A2 mimetic,
      desensitizes the TxA2/prostaglandin (PG) H2 receptor and sensitizes
      adenylylcyclase to stimuli, such as PGI2 or PGD2. This phenomenon may occur in
      vivo in conditions associated with platelet activation. Tx synthase inhibitors
      produce a rediversion of arachidonic acid metabolism toward the adenylylcyclase
      stimulators PGD2 and PGI2. We assessed whether the desensitization of the
      platelet TxA2 receptor affects the antiplatelet activity of drugs acting on the
      arachidonic acid metabolic cascade. A Tx synthase inhibitor (OKY046), a PGH2/TxA2
      receptor antagonist (BM13.505), their combination, two dual Tx synthase
      inhibitors/receptor antagonists (picotamide and ridogrel) or the cyclooxygenase
      inhibitor aspirin were studied. OKY046 alone or combined with BM13.505,
      picotamide and ridogrel, as well as PGD2, but not BM13.505 or aspirin, caused a
      stronger inhibition of platelet aggregation with desensitized platelets; this
      effect was potentiated by the phosphodiesterase inhibitor HL725 and was almost
      abolished by the adenylylcyclase inhibitor SQ22,536. A larger increase in cAMP
      synthesis was observed in desensitized as compared with control platelets with a
      Tx synthase inhibitor or with dual Tx synthase inhibition/receptor antagonism. No
      differences were observed in the degree of TxA2 suppression. Our observations
      showed that Tx synthase inhibitors exerted a stronger antiaggregatory effect in
      TxA2 receptor-desensitized platelets due to a stimulation of adenylylcyclase.
      This can be of relevance in the treatment of thrombotic disorders in which an in
      vivo desensitization of platelet TxA2 receptors takes place.

PMID- 8531122
TI  - Acetaminophen does not decrease hepatic 3'-phosphoadenosine 5'-phosphosulfate in
      mice.
AB  - Capacity-limited sulfation of chemicals is thought to be due to the limited
      availability of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the cosubstrate for
      sulfation, which in turn is limited by the availability of its precursor,
      inorganic sulfate. Because this concept evolved from experimental data obtained
      from rats, and species differences have also been reported on acetaminophen (AA)
      sulfation, this study examined the effects of AA on PAPS and sulfate
      concentrations in mice, another widely used experimental animal. AA lowered serum
      and liver sulfate concentrations approximately 50% in mice. However, contrary to
      observations in rats, AA (0-600 mg/kg i.p.) did not decrease hepatic PAPS
      concentrations in mice. In summary, these studies demonstrate that AA decreases
      serum and liver sulfate concentrations, but does not decrease hepatic PAPS
      concentrations in mice. These data indicate that 1) hepatic sulfation of high
      dosages of AA in mice is not limited by the availability of PAPS, and 2) there
      are significant species differences in the regulation of AA sulfation between
      rats and mice.

PMID- 8531123
TI  - Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol
      treated rats.
AB  - Reperfusion injury was studied in blood-free perfused livers from fat-loaded,
      ethanol-treated rats. Rats were pair-fed a modified Lieber-DeCarli liquid diet
      containing 36% calories as ethanol or isocaloric maltose-dextrin for 4 to 5
      weeks. Reperfusion injury to the liver, which occurs in previously hypoxic
      regions upon reintroduction of oxygen, was studied in a low-flow, reflow
      perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal
      levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol
      treatment elevated values to 37 IU/g/h. Pretreatment of rats with gadolinium
      chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized
      lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers from
      both groups. Rates of malondialdehyde production were 144 and 166 nmol/g/h during
      reperfusion in control and alcohol-treated rats, respectively, but values reached
      only 54 and 79 nmol/g/h after GdCl3 treatment. Interestingly, a typical
      PBN/carbon-centered free radical adduct signal was detected in bile of livers
      from ethanol-treated rats, but not in controls or ethanol-treated rats given
      GdCl3. Portal pressure increased during the reperfusion period in livers from
      alcohol-treated rats, although not in controls, and GdCl3 reduced it
      significantly. Taken together, these data indicate that reperfusion injury is
      greater in fatty livers from alcohol-treated rats in a blood-free model.
      Inactivation of Kupffer cells minimized reperfusion injury in both control and
      alcohol-treated rats, most likely by diminishing lipid peroxidation thereby
      improving hepatic microcirculation.

PMID- 8531124
TI  - Pharmacology of L-754,142, a highly potent, orally active, nonpeptidyl endothelin
      antagonist.
AB  - L-754,142, (-)-N-(4-iso-propylbenzenesulfonyl)-alpha-(4-carboxyl-2-n-propy
      lphenoxy)-3,4- methylenedioxyphenylacetamide, is a potent nonpeptidyl endothelin
      antagonist (e.g., Ki: cloned human ETA = 0.062 nM: cloned human ETB = 2.25 nM),
      with high specificity for endothelin receptors. In vitro, L-754,142 is a potent
      antagonist of ET-1-induced phosphatidyl inositol hydrolysis in Chinese hamster
      ovary cells expressing cloned human endothelin receptors (IC50: hETA = 0.35 nM;
      hETB = 26 nM) and of ET-1 induced contractions in rabbit iliac artery rings (pA2
      = 7.74) and rat aortic rings (pA2 = 8.7). In vivo, L-754,142 is a potent and
      specific antagonist of exogenously administered ET-1 or big ET-1, L-754,142 fully
      protects against ET-1-induced lethality in mice (AD50 = 0.26 mg/kg i.v.). The
      pressor response to big ET-1 in the anesthetized ferret is blocked by this
      compound with an ED50 value of 0.019 mg/kg i.v. L-754,142 also blocks the pressor
      response to big ET-1 in the conscious rat with ED50 values of 0.30 mg/kg i.v. and
      0.56 mg/kg p.o. The duration of action of L-754,142 in this rat model is more
      than 12 hr after an oral dose of 3 mg/kg. In summary, L-754,142 is a potent,
      orally active ET antagonist with a long duration of action in several in vivo
      models.

PMID- 8531125
TI  - Potent and selective inactivation of human liver microsomal cytochrome P-450
      isoforms by L-754,394, an investigational human immune deficiency virus protease
      inhibitor.
AB  - L-754,394, N-[2(R)-hydroxy-1(S)-indanyl]-5-[2(S)-(1,1-dimethylethylaminocarbonyl
      )-4- [(furo[2,3-b]pyridin-5-yl)methyl]piperazin-1-yl]-4(S)-hydroxy-2(R) -
      phenylmethylpentanamide, is a potent and specific inhibitor of the human immune
      deficiency virus (HIV) protease. The drug selectively inhibited human liver
      microsomal CYP 3A4-dependent testosterone 6 beta-hydroxylase and CYP 2D6
      dependent bufuralol 1'-hydroxylase activities in a time- and concentration
      dependent manner in the presence of an NADPH-generating system. L-754,394 was
      found to be a very potent inactivator of CYP 3A4. Thus, for testosterone 6 beta
      hydroxylase, the inactivation kinetic constants, Kl and kinact, were 7.5 microM
      and 1.62 min-1, respectively, and the partition ratio (moles product formed per
      moles enzyme inactivated) was approximately 1.35. To a lesser extent, L-754,394
      also was an inactivator of CYP 2D6, for which the corresponding values for Kl,
      kinact and partition ratio were 32 microM, 0.18 min-1 and 40, respectively. CYP
      3A4 inactivation was reduced markedly by ketoconazole, a selective CYP 3A4
      inhibitor. Similarly, CYP 2D6 inactivation also was prevented by quinidine, a
      specific competitive inhibitor of this isoform. However, exogenously added
      nucleophiles (GSH, semicarbazide and N-acetylcysteine) failed to protect against
      P-450 inactivation. These results suggest that the inactivation process likely is
      mediated by a reactive metabolite of L-754,394 that alkylates, and thereby
      destroys, the enzyme. Furthermore, this electrophilic intermediate may not be
      released into the medium before the inactivation event.

PMID- 8531126
TI  - Opioid antinociception in a rat model of visceral pain: systemic versus local
      drug administration.
AB  - Antinociceptive effects of systemically or locally administered opioid mu, kappa
      and delta agonists were evaluated in a rat model of visceral pain.
      Resiniferatoxin (RTX, 3 nmol), a capsaicin-like mutant, produced abdominally
      directed grooming behavior after direct administration into the urinary bladder
      (intravesical, Lves.) by indwelling cannula. Systemic (s.c. or i.p.) pretreatment
      with the mu agonists morphine or [D-Ala2, NMePhe4, Gly-ol]enkephalin (Damgo), the
      kappa agonists trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]
      benzeneacetamide (U50,488) or [5R-(5,7,8-beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1
      oxaspiro[4,5]dec - 8-yl]-4-benzofuranacetamide (CI-977), or the nonpeptidic delta
      agonist (+/-)-4-((alpha-R*)-alpha-((2S*,5R(*)-4-Allyl-2,5-dimethyl-1-
      piperazinyl)-3-hydroxybenzyl)-N, N-diethylbenzamide (BW373U86) dose-dependently
      decreased RTX-induced abdominal licking; such antinociception was selectively
      blocked by the appropriate receptor-selective antagonists beta-funaltrexamine
      (mu), nor-binaltorphimine (kappa) and naltrindole (delta). Local (i.ves.)
      BW373U86, [D-Ala2,Glu4]deltorphin (DELT II) and Cl-977 also significantly
      decreased RTX-induced licking. Intracerabroventricular quaternary naloxone
      partially blocked the effects of systemic morphine, but not that of CI-977 or
      BW373U86. Intraperitoneal quaternary naloxone blocked the effect of local and
      systemic BW373U86 but not that of local or systemic CI-977; systemic morphine was
      partially blocked. Thus, systemic mu, kappa and delta agonists all produced
      antinociception against a novel visceral chemical stimulus in the rat. Local CI
      977 also produced antinociception, but the only compound clearly acting at
      peripheral opioid receptors was BW373U86, a delta agonist. This study suggests
      that opioid delta receptors may be present on bladder nociceptive afferents and
      may be activated for production of peripheral analgesia.

PMID- 8531127
TI  - Angiotensin II tachyphylaxis in the guinea pig ileum and its prevention: a
      pharmacological and biochemical study.
AB  - Angiotensin II (AII) tachyphylaxis occurs in the guinea pig ileum, but is not
      induced by analogs lacking the N-terminal amino group or the Arg2 guanidino
      group. Both AII and Lys2AII increased cell inositol trisphoshate content in
      cultured intestinal smooth muscle cells. Protein kinase C inhibition by
      staurosporine or downregulation by prolonged incubation with phorbol reverted
      tachyphylaxis of the inositol trisphoshate response, but not that of the Na+
      uptake response, indicating that the uncoupling of the phosphoinositide signal
      system by protein kinase C did not involve all processes distal to receptor
      activation. Tachyphylaxis of the Na+ uptake response was prevented when receptor
      internalization was blocked by reduction of the temperature (4 degrees C) or by
      pretreatment of the cells with phenylarsine oxide. Acid washings, which prevented
      tachyphylaxis of the 24Na+ influx response, also prevented tachyphylaxis of the
      contractile response of the guinea pig ileum to AII. Although these findings
      suggest that sequestration or internalization of the AII receptor might be
      involved in AII tachyphylaxis, binding of [125I]AII and of [125I]Lys2AII to the
      cells was equally unaffected by repeated administrations of the peptides. The
      results suggest that conformational change of the AII-receptor complex within the
      plasma membrane, but not internalization, is the most important factor
      responsible for tachyphylaxis.

PMID- 8531128
TI  - Serotonergic modulation of the behavioral effects of cocaine in the squirrel
      monkey.
AB  - The behavioral effects of cocaine (0.03-3.0 mg/kg) and several selective
      serotonin (5HT) uptake inhibitors, direct agonists and antagonists were
      determined in squirrel monkeys trained to respond under a fixed-interval (FI)
      schedule of stimulus termination and a second-order schedule of i.v. drug self
      administration. Intermediate doses of cocaine increased fixed-interval response
      rate markedly, and higher doses decreased response rate below control (nondrug)
      values. The i.v. self-administration of cocaine (0.025-1.0 mg/injection)
      maintained schedule-appropriate responding over a range of doses, and response
      rate under the second-order schedule was a function of drug dose. In contrast,
      none of the 5HT uptake inhibitors (alaproclate, clomipramine and fluoxetine) or
      direct agonists ((+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, (+/-)-8
      hydroxy-2-(di-N-propylamino) tetralin and quipazine) increased fixed-interval
      response rate, nor did the 5HT uptake inhibitors maintain self-administration. In
      drug interaction studies, the 5HT uptake inhibitors and quipazine produced an
      insurmountable attenuation of the behavioral-stimulant effects of cocaine,
      whereas the 5HT antagonists (ketanserin, mianserin and ritanserin) with high
      affinity for 5HT2 binding sites enhanced the behavioral-stimulant effects of low
      or intermediate doses of cocaine. Additionally, administration of ritanserin
      increased response rate for i.v. for self-administration of cocaine over a range
      of cocaine doses. The pharmacological profile of effects of selective 5HT uptake
      inhibitors and direct agonists indicates that the behavioral-stimulant and
      reinforcing effects of cocaine do not depend on inhibition of 5HT uptake, whereas
      the drug interactions suggest that the serotonergic system can modulate specific
      behavioral effects of cocaine.

PMID- 8531129
TI  - Participation of delta opioid receptor subtypes in the stimulation of adenylyl
      cyclase activity in rat olfactory bulb.
AB  - A number of recent investigations have proposed the existence of two
      pharmacologically distinct delta opioid receptor subtypes, named delta 1 and
      delta 2. In the present study, we have investigated the involvement of the two
      delta receptors in the opioid stimulation of adenylyl cyclase activity in rat
      olfactory bulb. In addition, we have conducted a similar investigation in rat
      striatum, where delta agonists are known to inhibit cyclic AMP formation. Both (D
      Ala2, Glu4) deltorphin (DELT), a delta 2 agonist, and [D-Pen2, D-Pen5] enkephalin
      (DPDPE), a delta 1 agonist, stimulated adenylyl cyclase activity in rat olfactory
      bulb in a concentration-dependent manner, DELT being 25-fold more potent than
      DPDPE. The selective delta 2 antagonist naltriben counteracted the stimulatory
      effects of both agonists with a potency about 10-fold higher than that of the
      selective delta 1 antagonist 7-benzylidenenaltrexone. Moreover, pretreatment of
      olfactory bulb membranes with the nonequilibrium antagonist naltrindole 5'
      isothiocyanate, which irreversibly blocks the delta 2 subtype, reduced the
      stimulatory effects of both DELT and DPDPE, whereas pretreatment with [D-Ala2,
      Leu5, Cys6]enkephalin, which binds covalently to delta 1 receptors, failed to
      affect the response to the agonists. Similar results were obtained in rat
      striatum. These data indicate that delta opioid receptors coupled to either
      stimulation or inhibition of adenylyl cyclase in two different brain areas
      predominantly belong to the delta 2 subtype.

PMID- 8531130
TI  - Effects of propofol on nociceptive response and power spectra of
      electroencephalographic and systemic arterial pressure signals in the rat:
      correlation with plasma concentration.
AB  - We applied simultaneous spectral analysis of electroencephalographic (EEG) and
      systemic arterial pressure signals in Sprague-Dawley rats to monitor the status
      of consciousness and cardiovascular functions during intravenous anesthesia with
      propofol and to assess their correlations with plasma propofol concentration. Our
      results support the hypothesis that a 'threshold' plasma concentration (1.7-1.8
      micrograms/ml) exists for propofol anesthesia. This threshold level, we further
      showed, may be attained by both i.v. bolus injection and continuous infusion,
      although the pharmacokinetic profiles, as well as EEG and hemodynamic correlates,
      may be different. Continuous, on-line power spectral analysis of EEG signals
      revealed that the degree of reduction in the power density of the theta and delta
      bands and root mean square value paralleled the level of anesthesia. Significant
      suppression of both alpha and beta components occurred only concomitant with EEG
      burst suppression. At the subanesthetic dose, i.v. infusion of propofol increased
      preferentially the power density of the theta and delta bands, suggesting the
      validity of including sedation as a nonhypnotic therapeutic application of
      propofol. We also found that appreciable cardiovascular suppression took place
      only upon anesthetic doses of propofol. Power spectral analysis of systemic
      arterial pressure signals indicated that this was accompanied by a progressive
      depression of spectral parameters that signify peripheral vascular resistance and
      baroreceptor reflex response.

PMID- 8531131
TI  - Evidence for dissimilar mechanisms of enhancement of inorganic and organic
      hydroperoxide cytotoxicity by L-histidine.
AB  - L-Histidine markedly increases inorganic and organic hydroperoxide-induced
      cytotoxicity and DNA single-strand breaks (SSBs) in Chinese hamster ovary cells.
      These effects were prevented by the iron chelator o-phenanthroline and were
      insensitive to the antioxidant N,N'-diphenyl-1,4-phenylenediamine. An excess of L
      glutamine, a competitive inhibitor of L-histidine uptake, prevented the L
      histidine-mediated enhancement of cytotoxicity induced by both inorganic and
      organic peroxides. L-Glutamine did not affect the level of DNA SSBs produced by
      H2O2/L-histidine, although it abolished the enhancement of SSB formation
      triggered by L-histidine in cells exposed to the organic peroxides. DNA SSBs
      generated by the organic hydroperoxides either alone or associated with L
      histidine were removed with superimposable kinetics, whereas those produced by
      H2O2 in the presence of the amino acid were repaired more slowly than SSBs
      produced by the oxidant alone. DNA double-strand breaks, which are considered to
      be highly cytotoxic, were detected only in cells treated with H2O2 and L
      histidine. Finally, L-histidine was shown to markedly increase the extent of
      mitochondrial damage produced by organic but not by inorganic hydroperoxides.

PMID- 8531132
TI  - The specific contribution of the novel alpha-1D adrenoceptor to the contraction
      of vascular smooth muscle.
AB  - With a selective antagonist, the specific contribution of the alpha-1D
      adrenoceptor (AR) to vascular smooth muscle contraction has been assessed. BMY
      7378 bound to membranes expressing the cloned rat alpha-1D AR with a > 100-fold
      higher affinity (K1 = 2 nM) than binding to either the cloned rat alpha-1A AR (Ki
      = 800 nM) or the hamster alpha-1B AR (Ki = 600 nM). BMY 7378 exhibited
      differential potency in inhibiting vascular smooth muscle contraction. In the rat
      aorta and iliac artery, BMY 7378 was a high-affinity antagonist, producing
      parallel shifts in the phenylephrine concentration-response curve. The
      dissociation constants for this compound by Schild analysis were 0.95 and 4 nM
      for the aorta and iliac artery, respectively. The slopes of these Schild plots
      were not significantly different from unity. BMY 7378 was a weak antagonist in
      the rat caudal, mesenteric resistance and renal arteries, with Schild slopes
      significantly < 1. With ribonuclease protection assays, alpha-1D mRNA was found
      in all blood vessels examined. These data suggest that (1) BMY 7378 is a
      selective alpha-1D AR antagonist that can be used in functional systems to assess
      the contribution of this receptor in vascular smooth muscle contraction; (2) the
      alpha-1D AR appears to play a major role in the contraction of the aorta and
      iliac artery; (3) despite the fact that the mRNA for the alpha-1D AR can be
      detected in the caudal, mesenteric resistance (4) and renal arteries, it does not
      appear to play a role in mediating contraction of these blood vessels; and (4)
      expression of alpha-1D mRNA in a particular artery does not ensure that this
      receptor is involved in regulating the contraction of that artery.

PMID- 8531133
TI  - In vivo injection of antisense oligodeoxynucleotides to G alpha subunits and
      supraspinal analgesia evoked by mu and delta opioid agonists.
AB  - For 5 consecutive days repeated intracerebroventricular (i.c.v.) administration
      of antisense oligodeoxynucleotides (ODNs) to G alpha subunit mRNAs was used to
      impair the function of mouse Gi1, Gi2, Gi3 and Gx/z regulatory proteins.
      Decreases of 20 to 60% on the G alpha-like immunoreactivity could be observed in
      neural structures of mouse brain, an effect that was not produced by a random
      sequence ODN used as a control. The ODN to Gi1 alpha subunits lacked effect on
      opioid-evoked analgesia. In mice injected with the ODN to Gi2 alpha subunits the
      antinociceptive activity of all the opioids studied appeared greatly impaired.
      The ODN to Gi3 alpha subunits reduced the effects of the selective agonists of
      delta opioid receptors, [D-Pen2,5]-enkephalin and [D-Ala2]deltorphin II.
      Conversely, the analgesia evoked by opioids binding mu opioid receptors, [D-Ala2,
      N-MePhe4,Gly-ol5]enkephalin and morphine, appeared consistently and significantly
      attenuated in mice injected with the ODN to Gx/z alpha. The effect of the
      neuropeptide beta-endorphine-(1-31) agonist at mu and delta receptors was also
      reduced by ODNs to Gi3 alpha or Gx/z alpha subunits. l.c.v. injection of
      antibodies directed to these G alpha subunits antagonized opioid-induced
      analgesia with a pattern similar to that observed for the ODNs. Thus, the mu and
      delta opiod receptors regulate different classes of G transducer proteins to
      mediate the analgesic effect of agonists. The in vivo antisense strategy and the
      use of specific antibodies to G alpha subunits gave comparable results,
      indicating that in the neural tissue the mRNAs and the G alpha subunits can be
      accessed by the corresponding ODNs and IgGs.

PMID- 8531134
TI  - Development of delta-opioid receptor subtypes and the regulatory role of weaning:
      radioligand binding, autoradiography and in situ hybridization studies.
AB  - Evidence from behavioral studies suggests that the process of weaning activates
      the development of a delta-opioid receptor subtype. We now report the influence
      of weaning on the development of delta receptors in the central nervous system
      assessed by membrane homogenate binding and autoradiography with selective delta
      radioligands and by in situ hybridization using a cRNA probe for the delta
      receptor. Binding was carried out by using [3H][D-Ala2]deltorphin I (DELT I),
      [3H]IIe5,6-deltorphin II (IIe5,6-DELT II) and [3H]naltrindole (NTI). [3H]IIe5,6
      DELT II and [3H]NTI labeled an equivalent number of sites in brain and spinal
      cord from both weaned and nonweaned 25-day-old rats. The number of sites labeled
      by [3H]DELT I was similar in nonweaned rats but significantly higher in the brain
      and cord from weaned animals. Furthermore, the ontogenetic profile of these three
      ligands was distinct. Quantitative autoradiography showed identical levels of
      [3H]IIe5,6-DELT II binding in all brain regions in weaned and nonweaned rats. In
      contrast, levels of [3H]DELT I binding were significantly higher in weaned rats
      and this difference was localized to the deep layers of the frontal-parietal
      cortex and to the pontine nucleus. In situ hybridization experiments showed no
      differences in delta-opioid receptor mRNA density between weaned and nonweaned
      groups in the regions in which binding differences were observed. Weaning
      stimulates the development of a subpopulation of delta receptors recognized by
      [3H]DELT I but not by [3H]IIe5,6-DELT II or NTI. This effect is localized to
      specific brain regions and does not appear to reflect increased synthesis of mRNA
      coding for the delta receptor.

PMID- 8531135
TI  - Inhibition of the rat cytochrome P450 3A2 by an antisense phosphorothioate
      oligodeoxynucleotide in vivo.
AB  - CYP3A2 is one of the most abundantly expressed cytochrome P450s (CYPs) in the rat
      liver and metabolizes numerous clinically important drugs. Studies were designed
      to examine efficacy, potency and specificity of antisense inhibition of CYP3A2 in
      vivo. Three phosphorothioate ODNs were used: 3A2-ATG, antisense to the CYP3A2
      mRNA translational start site; 3A2-REV, 5' to 3' reverse sequence of 3A2-ATG; and
      C-MYC, antisense to the C-MYC mRNA translational start site. Midazolam (MZ) sleep
      times were used as CYP3A2-specific in vivo marker in male Sprague-Dawley rats.
      Administration of 1 mg/day 3A2-ATG for 2 days i.p. significantly increased MZ
      sleep times from 22.4 +/- 0.4 (saline) to 35.3 +/- 1.5 min. Administration of
      equivalent doses of noncomplementary 3A2-REV or C-MYC produced no significant
      changes in MZ sleep times (22.4 +/- 0.6 and 22.8 +/- 1.3, respectively). Liver
      microsomal erythromycin demethylase activity, a specific CYP3A2 assay, was
      significantly decreased from 124 +/- 13 mumol/mg per min in saline controls to
      63.8 +/- 8 in 3A2-ATG-treated rats. Enzyme activities for CYPs 2E1, 1A1/2 and
      2B1/2 were not significantly different between saline controls and 3A2-ATG
      treated animals. The control ODNs 3A2-REV and C-MYC had no significant changes in
      enzymatic activities compared to saline. Western blot analysis revealed decreases
      in CYP3A2 protein but not CYP2B1 protein in 3A2-ATG rat microsomes compared to
      controls. These studies demonstrate for the first time that antisense ODNs can
      effectively, potently, and specifically inhibit CYP3A2 in vivo.

PMID- 8531136
TI  - Inactivation and degradation of human cytochrome P4502E1 by CCl4 in a transfected
      HepG2 cell line.
AB  - Treatment with CCl4 in vivo labilizes cytochrome P4502E1, inactivating the enzyme
      and enhancing its degradation. To investigate the mechanism of CCl4-induced
      degradation of human CYP2E1, a recently-established MVh2E1-9 cell line, which
      constitutively expresses the human CYP2E1 in HepG2 cells was used. CCl4 inhibited
      oxidation of p-nitrophenol in isolated microsomes from MVh2E1-9 cells suggesting
      that CCl4 could be metabolized in vitro by the system; however, CCl4 did not
      promote lipid peroxidation under these conditions. Treatment of the MVh2E1-9
      cells in situ with 2 mM CCl4 for 24 hr caused a 30 to 50% loss of both enzyme
      activity and 2E1 protein. Treatment with cycloheximide at the same time to
      inhibit constitutive protein synthesis showed a more prominent loss of 2E1
      activity and protein. CCl4-induced degradation of CYP2E1 could be prevented by
      ligands and substrates of 2E1. N-acetylcysteine, N-t-butyl-alpha-phenylnitrone or
      propylgallate did not significantly prevent CCl4-induced inactivation or
      degradation of 2E1. After treatment with 14C-labeled CCl4, there was increased
      radioactive adduct formation in MVh2E1-9 cells compared to control cells lacking
      CYP2E1. This increase was completely prevented by 4-methylpyrazole and ethanol
      indicating its dependence on CYP2E1. These results suggest that the human CYP2E1
      expressed in the MVh2E1-9 cell line metabolizes CCl4, generating reactive species
      at the active site that directly inactivate the enzyme and also labilize P450 for
      degradation by proteases present in the HepG2 cells. Lipid peroxidation is not
      required for the CCl4-induced inactivation and degradation of CYP2E1 in these
      cells.

PMID- 8531137
TI  - Cloning and pharmacological characterization of the rabbit bradykinin B2
      receptor.
AB  - Degenerate primers, corresponding to consensus sequences of third and sixth
      transmembrane domains of G protein-coupled receptor superfamily, were used for
      the polymerase chain reaction amplification and consecutive characterization of G
      protein-coupled receptors present in cultured rabbit aortic smooth muscle cells.
      One of the isolated resulting fragments was highly homologous to the
      corresponding region of the bradykinin (BK) B2 receptor cloned in other species.
      The polymerase chain reaction fragment was used to screen a rabbit genomic
      library, which allowed the identification of an intronless 1101-nucleotide open
      reading frame which codes for a 367-amino acid receptor protein. The rabbit B2
      receptor sequence is more than 80% identical to the ones determined in three
      other species and retain putative glycosylation, palmitoylation and
      phosphorylation sites. In the rabbit genomic sequence, an acceptor splice
      sequence was found 8 base pairs upstream of the start codon. Northern blot
      analysis showed a high expression of a major transcript (4.2 kilobases) in the
      rabbit kidney and duodenum, and a less abundant expression in other tissues.
      Southern blot experiments suggest that a single copy of this gene exists in the
      rabbit genome. The cloned rabbit B2 receptor expressed in COS-1 cells binds
      [3H]BK in a saturable manner (KD 2.1 nM) and this ligand competes with a series
      of kinin agonists and antagonist with a rank order consistent with the B2
      receptor identity. The insurmountable character of the antagonism exerted by Hoe
      140 against BK on the rabbit B2 receptor, previously shown in pharmacological
      experiments, was confirmed in binding experiments with the cloned receptor
      expressed in a controlled manner. By contrast, Hoe 140 competed with [3H]BK in a
      surmountable manner for the human B2 receptor expressed in COS-1 cells. The
      cloning of the rabbit B2 receptor will be useful notably for the study of the
      structural basis of antagonist binding and for studies on receptor regulation in
      a relatively large animal.

PMID- 8531138
TI  - Cloning and characterization of a rat H+/peptide cotransporter mediating
      absorption of beta-lactam antibiotics in the intestine and kidney.
AB  - A complementary DNA (cDNA) encoding the rat H+/peptide cotransporter (PepT1) was
      isolated, and the transport characteristics of orally active beta-lactam
      antibiotics were assessed by measuring uptake into Xenopus oocytes expressing the
      rat PepT1. The rat PepT1 cDNA encoded a 710-amino acid protein with 77% identity
      to the rabbit PepT1. The message for rat PepT1 was approximately 2.9 kilobases
      and was found predominantly in the small intestine, whereas reverse transcription
      polymerase chain reaction amplification revealed that the message was expressed
      both in the small intestine and in the kidney cortex. The 75-kDa protein was
      identified by translation of in vitro synthesized transcript of rat PepT1 cDNA by
      use of rabbit reticulocyte lysates and by Western blot analysis with a specific
      antibody against the rat PepT1. When expressed in Xenopus oocytes, rat PepT1
      stimulated the uptake of ceftibuten (anion) and cephradine (zwitterion) in the
      presence of an inward H+ gradient, and the expressed uptake was inhibited by
      excess dipeptides. Kinetic analysis revealed that ceftibuten has 14-fold higher
      affinity for the rat PepT1 than cephradine. These findings suggest that the rat
      PepT1 mediates H(+)-coupled uphill transport of the oral beta-lactam antibiotics
      across the brush-border membranes of intestinal and renal proximal tubular cells.

PMID- 8531139
TI  - 5-Hydroxytryptamine2A (5-HT2A) receptor desensitization can occur without down
      regulation.
AB  - The connection between agonist-induced desensitization and down-regulation of 5
      hydroxytryptamine2A (5-HT2A) receptors was examined in a clonal cell line that
      stably expresses the 5-HT2A receptor. Brief (2-hr) and prolonged (24-hr) exposure
      to the agonist quipazine or the agonist 4-iodo-(2,5-dimethoxy)-
      phenylisopropylamine (DOI) diminished 5-HT2A receptor-mediated phosphoinositide
      hydrolysis; no change in 5-HT2A receptor number or affinity was measured after 24
      hr of exposure to DOI or quipazine. Immunohistochemical studies demonstrated that
      a 24-hr exposure to DOI did not alter surface 5-HT2A receptor immunoreactivity.
      Western blot analysis with G alpha q- and G alpha 11-selective antibodies
      indicate that a 24-hr agonist exposure did not alter the levels of phospholipase
      C-dependent G proteins. These results suggest that desensitization after
      prolonged DOI exposure can occur via a process independent of the levels of
      phospholipase C-coupled G proteins. Studies with a mutant 5-HT2A receptor (F340L)
      indicated that binding per se is not sufficient for desensitization. Down
      regulation of the protein kinase C isozymes alpha and epsilon by overnight
      exposure to phorbol-12,13-dibutyrate attenuated the intermediate phase (i.e.,
      after 2-6 hr of agonist exposure) of DOI- and quipazine-induced desensitization.
      These results indicate that the intermediate phase of DOI-induced desensitization
      is mediated by the alpha- and/or epsilon-protein kinase C isozymes but that
      neither is involved in the later phase (i.e., after 24 hr of agonist exposure) of
      desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531140
TI  - Distribution of 1,3-bis(2-chloroethyl)-1-nitrosourea and tracers in the rabbit
      brain after interstitial delivery by biodegradable polymer implants.
AB  - Intracranial tumors, such as glioblastoma multiforme and astrocytomas, are among
      the most aggressive and difficult to cure. In the present study, we evaluated the
      intracranial distribution of released agents during the first 3 days after
      implantation. Polymer implants containing [3H]-1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU), [3H]dextran (MW 70,000) or [14C]iodoantipyrene (IAP) were
      implanted into the brains of rabbits; autoradiography was used to measure the
      distribution of radiolabels within the brain at 6, 24 and 72 hr after
      implantation. For all of the agents studied, the majority of the radioactivity
      was found within the region 1 to 2 mm from the surface of the polymer. Dextran,
      however, penetrated farther into the brain than either IAP or BCNU. The
      distribution of radiolabel on an anteroposterior axis was determined by examining
      serial coronal images: after 72 hr, significant radioactivity (< 2 S.D. above
      background) extended > 17 mm in animals with [3H]dextran implants and
      approximately mm in animals receiving [3H]BCNU or [14C]IAP. Concentration
      profiles were also measured on coronal images obtained at the implant site:
      radioactivity dropped to a 10% maximum value 1.7 mm from the surface of the
      pellet in [3H]dextran-treated animals and < 1.2 mm in [3H]BCNU or [14C]IAP
      treated animals. Measured concentration profiles near the polymer were compared
      to mathematical models of drug diffusion and elimination. These results
      demonstrate that the majority of agents delivered into the brain by
      intracranially implanted polymers accumulates in the tissue within 1 to 2 mm of
      the implant, but that the size of the treated region depends on physicochemical
      properties of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531141
TI  - The expression of alpha 1 adrenoceptor subtypes changes with age in the rat
      aorta.
AB  - Previous studies showed that alpha 1 adrenoceptor-mediated contractile responses
      change with age in the rat aorta, becoming more sensitive to Ca++ channel
      blockers and less sensitive to chlorethylclonidine (CEC), suggesting a change in
      the alpha 1 adrenoceptor subtypes that are present. In this study, alpha 1
      adrenoceptor density and alpha 1 adrenoceptor subtypes were measured in the
      Fischer 344 rat aorta during aging. Aortic alpha 1 adrenoceptor densities,
      determined by saturation binding of 2-[beta-(4-hydroxy-3
      [125I]iodophenyl)ethylaminomethyl] tetralone ([125I]-HEAT), were 47, 41 and 45
      fmol/mg protein in 1-,6- and 24-month-old rats, respectively. The noncompetitive
      antagonist CEC completely blocked [125I]-HEAT binding in aortas from 1-month-old
      rats but inhibited binding only partially in aortas from older rats. Two binding
      sites were detected for norepinephrine and for WB4101 in all ages. The low
      affinity constants for WB4101 (31-51 nM) were consistent with those for the alpha
      1b adrenoceptor subtype, and this binding site decreased with age. The high
      affinity constant for WB4101 (1.4 nM) in 1-month-old aorta was consistent with
      that for alpha 1d adrenoceptor subtype, whereas the high-affinity constants (0.03
      nM) in 6- and 24-month-old aortas were consistent with those for the alpha 1a
      adrenoceptor subtype. At least three alpha 1 adrenoceptor subtypes appear to be
      colocalized in the rat aorta, so the binding affinities may reflect binding to
      more than one subtype. This makes it difficult to identify denfinitively the
      subtypes based on their radioligand binding characteristics.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8531142
TI  - Long-term stimulation of nicotinic receptors is required to increase
      proenkephalin A mRNA levels and the delayed secretion of [Met5]-enkephalin in
      bovine adrenal medullary chromaffin cells.
AB  - The effects of nicotine on the transcriptional activity of the proENK gene,
      proenkephalin A (proENK) mRNA levels, and the secretion of [Met5]-enkephalin (ME)
      were studied in bovine adrenal medullary chromaffin (BAMC) cells. Nicotine (10
      microM) caused an immediate secretion (within 1 hr) of ME followed by a delayed
      secretion (12-24 hr after treatment) into the medium. Posttreatment with the
      cholinergic antagonists, hexamethonium (1 mM) and atropine (1 microM), up to 6 hr
      after the nicotine treatment significantly inhibited the delayed secretion of ME
      induced by nicotine. However, nicotine-induced long-term secretion of ME was not
      affected when cholinergic antagonists were added 9 or 12 hr after the nicotine
      treatment. Long-term (24 hr) stimulation of BAMC cells with nicotine also
      increased proENK mRNA level. This nicotine-induced response was inhibited by
      posttreatment with cholinergic antagonists 0.5, 1, 3 and 6 hr after the nicotine
      treatment. As with the secretion experiments, these cholinergic antagonists did
      not affect the nicotine-induced responses when they were added at 9 and 12 hr.
      Posttreatment with nimodipine (1 microM), calmidazolium (1 microM) or KN-62 (5
      microM) up to 6 hr after the nicotine treatment significantly inhibited the
      increases of the long-term secretion of ME and proENK mRNA level induced by
      nicotine. However, these agents were ineffective in blocking the long-term
      secretion of ME and proENK mRNA level induced by nicotine when BAMC cells were
      posttreated after 9 and 12 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531143
TI  - Pharmacological studies of the regulation of chronic FOS-related antigen
      induction by cocaine in the striatum and nucleus accumbens.
AB  - Previous work has demonstrated that chronic administration of cocaine induces
      apparently novel Fos-like transcription factors, termed chronic Fras (Fos-related
      antigens), in the rat striatum and nucleus accumbens. Induction of these proteins
      is associated with prolonged increases in AP-1 DNA binding activity that parallel
      the long half-life of the chronic Fras in brain. The goal of the present study
      was to characterize pharmacologically the regulation of chronic Fra induction by
      cocaine. Chronic Fra induction was examined with respect to the cocaine dose,
      time course and administration intervals used. Cocaine was found to induce the
      chronic Fras over widely differing treatment regimens in the striatum and nucleus
      accumbens, although clear differences between the two brain regions were
      observed. In general, maximal induction occurred with moderate treatment
      conditions, with more or less intensive treatments resulting in lower levels of
      chronic Fras. The pharmacological mechanisms underlying cocaine induction of the
      chronic Fras were also investigated. Pretreatment with a D1 receptor antagonist,
      which did not affect chronic Fra levels by itself, attenuated cocaine induction
      of the chronic Fras in striatum and nucleus accumbens. In contrast, treatment
      with a D2 receptor antagonist alone greatly induced chronic Fra levels, with no
      further increase seen in response to combined treatment with cocaine. Combined
      treatment with D1 and D2 receptor agonists, or with amphetamine, led to a strong
      induction of chronic Fras. Similarly, repeated treatment with a specific dopamine
      transporter inhibitor increased chronic Fra levels, whereas treatment with a
      specific serotonin or norepinephrine transporter inhibitor failed to produce this
      effect. These results support an important role for dopaminergic
      neurotransmission in the induction of chronic Fras by cocaine. Taken together,
      the results of the present study provide a more complete understanding of the
      pharmacological properties underlying cocaine regulation of the chronic Fras,
      which will assist in identifying the functional role played by these proteins in
      cocaine action.

PMID- 8531144
TI  - Metallothionein expression and resistance to cisplatin in a human germ cell tumor
      cell line.
AB  - Expression of intracellular metallothionein (MT) has been linked to cis
      diamminedichloroplatinum (cDDP) resistance in human germ cell tumor cell lines.
      To determine whether exposure to cDDP would select for cells with increased MT
      expression, the MT content of the human teratocarcinoma cell line T7800 was
      measured after development of resistance to cDDP by exposure to progressively
      higher drug concentrations (6.25-25 microM). cDDP-resistant cells (T7800R) had
      significantly higher MT mRNA and MT protein, increased resistance to killing by
      cDDP and altered in vitro growth kinetics compared to parental T7800 cells. cDDP
      resistance in a variety of other human tumor cell lines correlated with MT
      content, with no significant difference in glutathione level. These data indicate
      that selection in vitro for cDDP resistance in human germ cell tumors coselects
      for cells with enhanced MT content. However, selected cells differed in
      characteristics other than MT content. They had a slower growth rate and,
      although the rank order of MT level in T7800, T7800R and other human tumor cell
      lines correlated very well with cDDP resistance, differences in the level of MT
      expression did not correspond with differences in the absolute level of cDDP
      resistance. These results suggest that increased MT expression is concomitant
      with increased cDDP resistance in a variety of human tumor cell lines. However,
      measured differences in MT levels may not accurately reflect the degree of cDDP
      resistance differences among those cells.

PMID- 8531145
TI  - [Basic study of calcium ion indicator for measurement of intracellular calcium
      ion].

PMID- 8531146
TI  - [Classification assisting program of single motor unit action potentials by
      BASIC].

PMID- 8531147
TI  - Complete dentures for a child with hypohidrotic ectodermal dysplasia: a clinical
      report.
AB  - Young children with anodontia caused by hypohidrotic ectodermal dysplasia not
      only have difficulties in eating and speaking but can also sense that their
      appearance is different than others. Enabling children with HED to look and act
      more like their peers through the use of well-fitting and functioning dentures
      with age-appropriate denture teeth will greatly assist in their transitioning
      into the school years. Although denture fabrication requires multiple patient
      appointments and good cooperation, it is shown that even young children can
      cooperate for the denture-making process. The desire to be like others who have
      teeth can be a motivator for cooperation in even the young child. Children should
      be given every opportunity to develop to their fullest potential. The dentist can
      make a significant contribution to the overall development and well being of a
      child with HED.

PMID- 8531148
TI  - Dimensional and formation analysis of a restorative ceramic and how it works.
AB  - In-Ceram ceramic appears to use conventional powder/liquid processing techniques
      to form the coping substructure; however, the process results in a near net-shape
      restoration with minimal sintering shrinkage. Scanning electron microscopy,
      Brunauer-Emmett-Teller analysis, particle size classification, and linear
      dimensional changes during sintering were used to analyze In-Ceram ceramic. In
      Ceram ceramic had a minimal linear shrinkage of 0.21% after the sintering of the
      alumina powder. This shrinkage can be readily compensated for by the expansion of
      conventional gypsum products and should result in acceptable clinical fits for In
      Ceram ceramic restorations. Theories and explanations were described to account
      for the near net-shape and high strength of In-Ceram. Continuous interpenetrating
      phase composite technologies were used to create a substantial increase in
      strength. Future applications of this technology are encouraging.

PMID- 8531149
TI  - A comparison of three wetting agents used to facilitate the pouring of dies.
AB  - This study compared the effect of a clinical surfactant and one of three
      laboratory surfactants used before pouring dies from elastomeric impression
      materials. A total of 154 impressions were recorded. Hydrosystem surfactant was
      used before the recording of 78 of these impressions. A total of 154 dies were
      poured with Wax-mate, Tensilab, or Hydrosystem surfactants and examined for
      surface voids by an examiner who was unaware which wetting agent was used. Six
      dies were grossly defective and discarded. When the Hydrosystem surfactant had
      not been used during impression recording there was no significant difference
      between Hydrosystem (mean 10.2 +/- 8.8 voids, n 25), Wax-mate (mean 13.1 +/- 14.4
      voids, n 25), and Tensilab (mean 14.9 +/- 11.6 voids, n 21) surfactants when the
      dies were poured. When Hydrosystem surfactant was used during impression
      recording, there was no significant difference between the number of voids on
      dies produced with Hydrosystem (mean 3.8 +/- 3.9 voids, n 26), Wax-mate (3.9 +/-
      3.3 voids, n 25), or Tensilab (3.7 +/- 4.9 voids, n 26) surfactants. However,
      each of the groups in which Hydrosystem surfactant was used before impression
      recording resulted in dies with significantly fewer voids than when it had not
      been used, independent of the surface wetting agent used in the pouring of dies
      (p < 0.05). To reduce the number of voids in laboratory dies, this in vitro study
      suggested that a topical surfactant should be used before an impression is
      recorded.

PMID- 8531150
TI  - A comparison of water temperatures for thermocycling of metal-bonded resin
      specimens.
AB  - The thermocycling test to evaluate the bonding durability of the adhesive
      interface against water penetration and thermal stress is one of the most
      important studies before clinical application of metal-bonded resin systems is
      performed. Researchers have adopted various water temperatures for thermocycling
      adhesion specimens, which makes a direct comparison with thermocycling data
      attained by other researchers difficult. In this study tensile and shear bond
      strengths of metal-bonded resin specimens were measured after 20,000 thermocycles
      with the temperatures of the hot bath at 50 degrees C, 60 degrees C, and 70
      degrees C. The results indicated that adhesive bonding strengths attained after
      thermocycling at 50 degrees C may be nearly comparable with those at 60 degrees
      C.

PMID- 8531151
TI  - Comparison of the torsional forces at failure for seven endodontic post systems.
AB  - Resistance to torsional forces is critical in restoration of endodontically
      treated teeth. Seven post designs (Flexi-Post, Flexi-Flange, Para-Post,
      AccessPost, World Post, Vlock, and Dentatus posts) were cemented in roots of
      natural teeth with zinc phosphate and Flexi-Flow cements, which resulted in 11
      different groupings that were subjected to torsional forces in a clockwise
      direction. In addition, clockwise and counterclockwise torque was applied to the
      Flexi-Post and Flexi-Flange systems cemented with zinc phosphate and Flexi-Flow
      cements. A total of 150 samples were prepared, and groups for this study were:
      group 1, Flexi-Post/zinc phosphate clockwise and counterclockwise; group 2, Flexi
      Post/Flexi-Flow clockwise and counterclockwise; group 3, Flexi-Flange/zinc
      phosphate clockwise and counterclockwise; group 4, Flexi-Flange/Flexi-Flow
      clockwise and counterclockwise; group 5, Para-Post/zinc phosphate clockwise;
      group 6, AccessPost/zinc phosphate clockwise; group 7, AccessPost/Flexi-Flow with
      grooved dentin clockwise; group 8, World Post/zinc phosphate clockwise; group 9,
      World Post/Flexi-Flow with grooved dentin clockwise; group 10, Vlock Post/zinc
      phosphate clockwise; and group 11, Dentatus post/zinc phosphate clockwise.
      Torsional forces for the groups ranged from 17 ounce-inches (Dentatus/zinc
      phosphate) to 81 ounce-inches (Flexi-Post/zinc phosphate). Flexi-Post and Flexi
      Flange threaded posts exhibited statistically greater resistance to torsional
      forces. Analyses were computed with one-way and three-way analysis of variance
      followed by Duncan's multiple range test. Duncan's multiple range test indicated
      that Flexi-Post/zinc phosphate/clockwise was similar to Flexi-Post/Flexi
      Flow/clockwise and that both had significantly higher torque levels than the
      other treatment conditions in the clockwise direction (p 0.0001). Dentatus/zinc
      phosphate/clockwise had significantly lower torque levels than the other
      treatment conditions (p 0.031).

PMID- 8531152
TI  - Nutritional adequacy of reported intake of edentulous subjects treated with new
      conventional or implant-supported mandibular dentures.
AB  - The nutrient content of the diet of edentulous patients who have various oral
      prostheses is of concern. This study compared baseline food records to those
      records kept semiannually for 3 years after treatment to ascertain whether
      nutrient intake of edentulous patients changed after they received new implant
      supported mandibular dentures (n = 41) or new conventional dentures (n = 30). No
      significant differences in intake of calories or of 27 nutrients were noted
      between the two groups (p > 0.01). A decline in the percent of calories from fat
      with a corresponding increase in carbohydrate calories within both groups (p <
      0.01) reflected a national trend; a slight decrease in calories was similarly
      observed (p < 0.02). More than 40% of patients in both groups were found to have
      inadequate intakes of dietary fiber, calcium, or both, and 25% to 50% had low
      intakes of vitamins A, E, D, B6 and/or magnesium. Intakes were similar to those
      reported for two age-matched populations.

PMID- 8531153
TI  - Organization, appointment planning, and surgery design in the treatment of the
      older patient.
AB  - As the proportion of the elderly in society increases and as more people retain
      teeth into old age, the type of dental treatment needed for this group will
      increase in both complexity and quantity. This article describes problems faced
      by the elderly such as mobility, fear, and medical conditions that may affect
      dental treatment either by increasing anxiety levels or by affecting duration or
      timing of appointments. The effects of visual impairment, hearing loss, and
      common medical conditions on elderly people are considered.

PMID- 8531154
TI  - Association between the interarch distance and food bolus size in the early phase
      of mastication.
AB  - The effects of food bolus size on interarch distance were examined in three
      dimensions with sphere-shaped gelatin (5 to 25 mm diameters). Interarch distance
      in the early phases of chewing indicated a significant linear relation (p <
      0.001) to food bolus size. The correlation coefficients were high particularly at
      the second and third opening sequences. At the first opening sequence during
      ingestion, interarch distance for small bolus of less than 15 mm was nearly
      constant and relatively wider than the bolus size. Practical information for
      determining the interincisal distance in prosthodontic treatment is provided.

PMID- 8531155
TI  - Geometric comparison of five interchangeable implant prosthetic retaining screws.
AB  - Eight geometric parameters of five interchangeable prosthetic retaining screws
      (#1-3i Implant Innovation-gold, #2-Impla-Med-gold, #3-Nobelpharma-gold, #4-3i
      Implant Innovation-titanium, and #5-Implant Support Systems-titanium) were
      recorded with an Amray 1000-B scanning electron microscope at x20 to x200
      magnification. Five screws of each type were measured and eight parameters were
      evaluated: (A) diameter of head, (B) screw length, (C) thread pitch, (D) major
      diameter, (E) neck diameter (F) length of neck, (G) crest width, and (H) root
      width. The Nobelpharma-gold prosthetic retaining screws served as controls. The
      results revealed significant differences between the control and test screws in
      all parameters except parameters C and G (ANOVA, p < 0.05) and Duncan's multiple
      range test (significance level 0.05). On the basis of these differences, it was
      concluded that interchanging prosthetic retaining screws can introduce unknown
      variables in treating patients.

PMID- 8531156
TI  - Factors to consider in selecting an occlusal concept for patients with implants
      in the edentulous mandible.
AB  - This article discusses the occlusal concepts when making implant-supported and
      implant-retained mandibular overdentures. The dentate or edentulous condition of
      the maxilla plays a significant role in this respect. If the maxilla is
      edentulous, balanced occlusion is indicated. In a maxillary Kennedy class I or II
      situation, either group function or balanced occlusion is advocated depending on
      the characteristics of the opposing dentition. When a complete dentition is
      present in the maxilla or in the case of a Kennedy class III or IV situation,
      mutually protected occlusion or group function is recommended depending on the
      length, position, and number of implants. It is stressed that detailed preimplant
      placement diagnosis and treatment planning are essential to obtain a high
      standard of treatment with overdentures supported and retained by implants.

PMID- 8531157
TI  - In vitro shear strength of bonded amalgam cores with and without pins.
AB  - This study compared the shear bond strength of resin-bonded amalgam with and
      without pins. The coronal third of 240 embedded posterior teeth was removed to
      expose a flat, nonretentive surface. Three Minikin pins were placed in the dentin
      in a triangular pattern 1 mm apart. Amalgam was condensed into a Delrin mold (4.2
      mm in diameter and 3 mm in height) positioned over each tooth. The adhesives
      Amalgam-bond, All-bond, Amalgambond with high-performance additive, Panavia EX,
      and Panavia with Photobond were the materials used to bond the amalgam to the
      dentin. Half of the samples were immersed in normal saline solution for 7 days
      and the others for 30 days. Shear bond strengths were recorded as the maximum
      load per cross-sectional area of the bonded surface with a testing machine with 1
      kN load cell and crosshead speed of 0.5 mm/min. A three-factor analysis of
      variance and Student-Newman-Keuls test (p = 0.05) identified Amalgambond with
      high-performance additive as the strongest adhesive in this study. The use of
      pins with or without adhesives increased the shear strength of amalgam samples
      significantly more than samples that used adhesives alone.

PMID- 8531158
TI  - Transverse bond strength of repaired acrylic resin strips and temperature rise of
      dentures relined with VLC reline resin.
AB  - This study measured the transverse strength of polymethyl methacrylate heat-cured
      resin samples repaired with Triad visible light-cured reline resin with and
      without bonding pretreatments and with autopolymerizing resin, and it measured
      the temperature rise of Triad resin during relining of complete dentures at
      various curing cycles. The results indicated that pretreatment with either
      monomer or Triad bonding agent improved the bond of the Triad visible light-cured
      reline resin to the heat-cured resin. However, the use of the monomer rather than
      bonding agent resulted in a stronger bond and obtained values similar to those of
      samples repaired with autopolymerizing resin. Polymerization of samples repaired
      with Triad resin in the curing unit for two cycles of 5 minutes with 1 minute
      between cycles resulted in bubble formation and severe distortion of the heat
      cured resin in the samples. Curing of the relined dentures for 10 minutes as
      recommended by the manufacturer raised the average peak temperature to 120
      degrees C. In addition, it was shown that interrupting the light curing cycle
      attenuated the temperature rise, but it also resulted in a relatively softer
      reline resin. A continuous light curing of at least 5 minutes with the adjunct
      temperature rise is required to reach 1-hour hardness of 21.8 Vickers hardness
      number of the Triad reline resin.

PMID- 8531159
TI  - A review of masticatory ability and efficiency.
AB  - Masticatory function can be assessed by chewing tests and questionnaires or
      personal interviews. Whereas the chewing tests allow the assessment of
      masticatory efficiency with some objectivity, questionnaires help evaluate a
      person's subjective responses about chewing ability. Epidemiologic studies
      indicate a subjective decrease in chewing ability with increasing degree of tooth
      loss, a trend that was confirmed in the literature. Of interest was that the
      subjective measures of masticatory ability are often overrated when compared with
      the functional tests. Masticatory function is a patient factor rather than a
      parameter that prosthetic treatment can qualify. It depends on a variety of
      personal and subjective factors that can hardly be influenced by the
      practitioner. This article describes and discusses scientific sociophysiologic
      and biomedical approaches to evaluating masticatory function.

PMID- 8531160
TI  - The effect of pH changes at the impression-stone cast interface during setting.
AB  - It is of great clinical significance to obtain a cast that reflects the optimal
      reproducibility of the irreversible hydrocolloid materials. This study
      investigated whether pH changes that occur during setting (as a single sequence
      of the chemical reactions that lead to gelation and the formation of the
      impression) are related to the reproducibility of irreversible hydrocolloids. The
      results indicated that as the pH range was increased for materials with alkaline
      pH values, the reproducibility improved. The opposite effect was noticed in
      materials with acidic pH values. It was also demonstrated that when the pH curve
      was in the acidic range, it was closer to the neutral pH values, and the
      reproducibility of the irreversible hydrocolloid was better.

PMID- 8531161
TI  - Study of the acceptability of lateral interocclusal records by a modular
      articulator.
AB  - Semiadjustable articulators are extensively used for routine restorative
      procedures. The instruments may be adjusted by lateral interocclusal records.
      However, it has been reported that semiadjustable articulators do not accept
      lateral interocclusal records from all patients. The Hanau modular system 194
      semiadjustable articulator was introduced to develop occlusion with minimal
      error. The manufacturer recommends that the instrument should be adjusted by
      means of lateral interocclusal records. This study investigated the acceptability
      of lateral interocclusal records. Sixty lateral interocclusal records were made
      for 30 edentulous subjects, and the acceptability of the records was evaluated by
      use of the split-cast mounting procedure. Out of 60 lateral interocclusal
      records, 52 (87%) records were accepted by the articulator. A Z test was used for
      two proportions and was statistically significant (p < 0.05).

PMID- 8531162
TI  - Deflection fatigue of cobalt-chromium, titanium, and gold alloy cast denture
      clasp.
AB  - The aim of this study was to determine the fatigue resistance of the cast clasps
      of removable partial dentures. The different commercial types of metals used
      included five cobalt-chromium alloys, pure titanium, one titanium alloy (Ti-6A1
      4V) and one gold alloy (type IV) that was either unhardened or age-hardened (n =
      5 per group). The test method used was a constant-deflection fatigue test in
      which the force required to deflect the clasp for 0.6 mm and the number of
      loading cycles required to fracture the clasp were determined. The fatigue
      fracture surface of the clasps was examined with a scanning electron microscope.
      The results revealed that a fatigue fracture occurred in the cobalt-chromium
      clasp after approximately 25,000 loading cycles, in the pure titanium clasps
      after 4500 loading cycles, in the titanium alloy clasp after 20,000 loading
      cycles, and in the gold alloy clasp after 21,000 loading cycles. The means
      differed significantly (p < 0.001). Activation of the clasp by bending it 0.5 mm
      increased the fatigue resistance of the cobalt-chromium alloy and gold alloy
      clasps but decreased the fatigue resistance of both pure titanium and titanium
      alloy clasps (p < 0.005). The results of this study suggest that significant
      differences exist in the fatigue resistance of removable denture clasps made from
      different commercial cast metals, which may cause loss of retention of the
      removable partial denture and clasp failures.

PMID- 8531163
TI  - The safety of dental mini-magnets in patients with permanent cardiac pacemakers.
AB  - To evaluate the safety of prosthetic mini-magnets, 12 patients treated with
      implanted cardiac pacemakers were examined. Small cylindric magnets were applied
      one, two, and three at a time to constant points on the pacemaker under
      electrocardiographic monitoring. No influence on the pacemaker was detected in
      nine of the patients, but limited changes were encountered in three patients.
      However, the changes disappeared when the magnets were moved 1 cm away. The
      conclusion was that the use of mini-magnets in dental care in patients with
      implanted pacemakers is safe and acceptable.

PMID- 8531164
TI  - Retentive characteristics of different dental magnetic systems.
AB  - It is necessary to recognize the retentive capabilities of magnetic systems to
      assess their clinical performance. This study determined the retentive
      characteristics of one open-field and two closed-field commercial dental magnetic
      systems. The effect of speed of separation and the space between the magnet and
      its keeper on the retention force were evaluated. The magnets and their
      respective keepers, embedded in acrylic resin blocks, were tested with fast and
      slow speeds of separation. The maximum retention values of the magnetic systems
      were tested with slow speed of separation. The fast speed of separation was
      designed to reflect mandibular movement. Various spaces were developed between
      the magnets and their respective keepers, and magnetic systems were tested only
      in slow speed of separation. The fast speed of separation dramatically lowered
      the retention force of each magnetic system. As the space increased between the
      magnet and keeper, the retention values diminished rapidly. While closed-field
      systems demonstrated higher retentive forces than the open-field system, the open
      field system was less affected by the various spaces.

PMID- 8531165
TI  - The modified swing-lock: a new approach.
AB  - The swing-lock removable partial denture (RPD) can address some specific
      partially edentulous situations better than conventional partial denture designs.
      The concept is recommended for maximizing stability and retention by access to
      more tooth surfaces and undercuts with the unique clasping mechanism offered by
      the incorporation of lock, hinge, and gate assemblies. Since its introduction,
      the swing-lock RPD has gained some degree of acceptance. However, it is
      infrequently used by clinicians because it is technique-sensitive, especially
      during hinge and lock fabrication, and the durability of the retentive element of
      the locking mechanism decreases with the progressive wear of the metal latch
      attachment. This article presents a new design for a swing-lock RPD by use of a
      vertical bar and plastic clip attachment as an alternative to the hinge and latch
      attachment. The suggested modification in the locking mechanism may overcome some
      of the problems associated with the conventional swing-lock RPD.

PMID- 8531166
TI  - Heat-cured silicone bimaxillary mouthguard.
AB  - A laboratory procedure for the construction of a heat-cured, silicone, custom
      made bimaxillary mouthguard for contact sports is described. Contours and
      vertical dimension are easier to control than with the conventional thermoformed
      product, and there is no danger of injury from contact between the maxillary and
      mandibular components.

PMID- 8531167
TI  - Direct impression coping for an implant system.

PMID- 8531168
TI  - Eye movements as a window into real-time spoken language comprehension in natural
      contexts.
AB  - When listeners follow spoken instructions to manipulate real objects, their eye
      movements to the objects are closely time locked to the referring words. We
      review five experiments showing that this time-locked characteristic of eye
      movements provides a detailed profile of the processes that underlie real-time
      spoken language comprehension. Together, the first four experiments showed that
      listeners immediately integrated lexical, sublexical, and prosodic information in
      the spoken input with information from the visual context to reduce the set of
      referents to the intended one. The fifth experiment demonstrated that a visual
      referential context affected the initial structuring of the linguistic input,
      eliminating even strong syntactic preferences that result in clear garden paths
      when the referential context is introduced linguistically. We argue that context
      affected the earliest moments of language processing because it was highly
      accessible and relevant to the behavioral goals of the listener.

PMID- 8531169
TI  - Constraint satisfaction as a theory of sentence processing.
AB  - Various problems with the constraint satisfaction model are discussed. It is
      argued that the empirical evidence presented in support of the model does not
      concern predictions of the model that diverge from those of depth-first (one
      analysis at a time) models. Several methodological problems are also noted. As a
      theory of sentence processing, the model is inadequate. It fails to account for
      the assignment of local structure, global structure, structure involving
      discontinuous dependencies, long-distance dependencies, and adjunct phrases. It
      makes incorrect predictions about the timing of syntactic analysis. Further,
      because syntactic structure is available only through activation of syntactic
      projections stored in the lexical entry of words, the model leaves entirely
      unexplained the myriad psycholinguistic findings demonstrating independence of
      lexical and syntactic structure (in Event Related Potential studies, code
      switching, pure syntactic priming, etc). Finally, the model is not restrictive or
      explanatory, providing an account that largely consists of post hoc correlations
      between frequency counts or subjects' ratings of sentences and processing time
      data for the same sentences.

PMID- 8531170
TI  - Effects of clausal structure on subject-verb agreement errors.
AB  - This paper explores the effect of manipulating the internal structure of a
      complex subject on the incidence of subject--verb agreement errors. Using the
      sentence completion task (Bock & Miller, 1991), this study followed up on
      Vigliocco and Nicol's (1995) finding that the syntactic distance between a head
      noun and a number-mismatching noun contained within a modifier has an impact on
      error incidence: the greater the distance, the lower the error rate. The study
      presented in this paper investigated whether this distance effect is purely
      syntactic; if so, then it would be expected that there would be fewer errors
      following The owner of the house which charmed the realtors... than following The
      owner of the house who charmed the realtors..., since in the latter, the mismatch
      is syntactically nearer the head noun. Results show no hint of a difference
      between the two, suggesting that the distance effect is more likely due to
      temporal distance rather than syntactic distance per se.

PMID- 8531171
TI  - On-line comprehension of VP-ellipsis: syntactic reconstruction and semantic
      influence.
AB  - We describe two experiments that explored the on-line processing of coordinated
      (e.g., The policemen defended himself and the fireman did [e] too, according to
      someone who was there) and subordinated VP-ellipsis (e.g., The policeman defended
      himself because the fireman did [e], according to someone who was there). Such
      constructions have two possible interpretations: The "sloppy" reading is that the
      fireman defended himself, where himself corefers with the fireman. The "strict"
      reading is that the fireman defended him, where him corefers with the policeman.
      In our experiments we examined the strict reading, and found different time
      courses of processing the coordinated and subordinated structures. In
      coordination we found immediate reaccess of the nonlocal subject at the gap. In
      subordinated structures we found the reaccess effect only downstream from the
      gap. We interpret these patterns as reflecting the automatic nature of gap
      filling in coordinated ellipsis, but in subordinated ellipsis a causal relation
      must be computed between the two clauses, " drawing out" reaccess of the filler.

PMID- 8531172
TI  - Participant roles and the processing of verbs during sentence comprehension.
AB  - This paper explores the nature of thematic information made available when a verb
      is accessed during sentence comprehension. Following Shapiro, Zurif, and Grimshaw
      (1987), a cross-modal lexical decision (interference) task was employed to
      examine whether either the number of argument structures or the number of
      participant (thematic) roles inherent in a verb cause an increase in processing
      load upon access of the verb. It was determined that there was no evidence for
      such an increased processing load covarying with the number of argument
      structures of the verb, at least for those verb types examined in this study.
      However, there was an increase in processing load as a direct function of the
      number of participant roles carried by the verb. It is concluded that the
      participant roles (thematic roles associated with the central meaning of the
      verb) are stored with the representation of a verb and are made immediately
      available upon access of the verb for further processing during comprehension.

PMID- 8531173
TI  - Equine melanocytic tumors: a retrospective study of 53 horses (1988 to 1991).
AB  - A study of 57 cutaneous melanocytic tumors from 53 horses revealed 4 distinct
      clinical syndromes: melanocytic nevus, dermal melanoma, dermal melanomatosis, and
      anaplastic malignant melanoma. Melanocytic nevus and anaplastic melanoma each had
      histopathologic features that distinguished them from dermal melanoma and dermal
      melanomatosis. Dermal melanoma and dermal melanomatosis were histologically
      similar but could be differentiated by their clinical features. Melanocytic nevi
      were diagnosed in 29 horses with an average age of 5 years; they were solitary,
      superficial masses that occurred in both grey and nongrey horses, and in which
      surgical excision was generally curative. Dermal melanomas were diagnosed in 20
      horses with an average age of 13 years; all horses of known coat color were grey.
      Eight horses with an average age of 7 years had 1 or 2 discrete dermal melanomas.
      Follow-up information was available for 6 horses; metastases occurred in 2
      horses, and surgical excision was apparently curative in 4 horses. Dermal
      melanomatosis was diagnosed in 12 grey horses with an average age of 17 years;
      all 6 of these horses evaluated had internal metastases. In 2 aged nongrey horses
      with anaplastic malignant melanoma, the tumors metastasized within 1 year of
      diagnosis. Two tumors with features of both melanocytic nevus and dermal melanoma
      remained unclassified.

PMID- 8531174
TI  - Hemostatic disorders in cats: a retrospective study and review of the literature.
AB  - Hemostasis profiles from 101 cats presented for medical or surgical evaluation to
      The Ohio State University Veterinary Teaching Hospital from 1986 through 1991
      were reviewed retrospectively; 69% were abnormal. Commonly identified
      abnormalities included a mixed hemostatic defect compatible with disseminated
      intravascular coagulation, thrombocytopenia, isolated prolongation of the
      activated partial thromboplastin time (APTT), and prolongation of both the APTT
      and one-stage prothrombin time. The most common disorders associated with
      abnormal hemostasis profiles in this study were liver disease, neoplasia, and
      feline infectious peritonitis.

PMID- 8531175
TI  - Diagnosis of inflammatory and infectious diseases of the central nervous system
      in dogs: a retrospective study.
AB  - The medical records of 220 dogs with inflammatory/infectious diseases of the
      central nervous system (CNS) were retrospectively examined. The aims of the study
      were to determine if clinical and clinicopathologic data (not including biopsy or
      necropsy examination) could distinguish inflammatory CNS diseases from diseases
      of other types, and to search for criteria allowing differentiation of specific
      inflammatory diseases. The signalment, historical findings, extraneural and
      neurological signs, and the lesion site contributed marginally to a specific
      diagnosis. Multifocal signs were only noticed in one third of the dogs with
      inflammatory/infectious diseases. Particular neurological abnormalities were more
      frequent in certain diseases than in others (eg, myoclonus was frequent in dogs
      with distemper, but it was also found in those with other
      meningoencephalomyelitides). Hematologic findings contributed to the diagnosis in
      certain conditions (eg, canine distemper encephalitis, protozoal
      encephalomyelitis, steroid-responsive meningitis-arteritis). Cerebrospinal fluid
      examinations, including immunoglobulin G index and cytology were useful to
      separate meningoencephalomyelitides from the other CNS diseases and to
      distinguish certain conditions from others. In most cases a specific diagnosis
      depended on a combination of clinical signs and ancillary diagnostic aids. Still,
      a specific diagnosis remained very difficult, if not impossible, in at least one
      third of the dogs.

PMID- 8531176
TI  - Myeloid and megakaryocytic hypoplasia in related standardbreds.
AB  - Myeloid and megakaryocytic bone marrow hypoplasia in association with moderate to
      profound neutropenia was observed in 8 young Standardbred horses sired by the
      same stallion; 7 horses were intermittently thrombocytopenic. Evaluation of
      serial neutrophil counts in 2 horses suggested that a cyclic variation in
      neutrophil numbers was present, that lymphocyte numbers increased when neutrophil
      counts decreased, and that platelet counts decreased when neutrophil counts
      decreased. Preliminary bone marrow cultures indicated that myeloid progenitor
      cells were present and that these cells were able to respond to exogenous growth
      factors by differentiating. A bone marrow microenvironment or growth factor
      defect is suspected. Seven of 8 horses died or were euthanized. One horse with
      moderate neutropenia and a normal platelet count has been racing for 3 years.
      Necropsies in 4 horses did not reveal a cause for the myeloid hypoplasia. A
      familial basis for the disease is suspected.

PMID- 8531177
TI  - Estimation of quantitative enzymuria in dogs with gentamicin-induced
      nephrotoxicosis using urine enzyme/creatinine ratios from spot urine samples.
AB  - The correlation between 24-hour urinary excretion of N-acetyl-beta-D
      glucosaminidase (NAG) and gamma-glutamyl transferase (GGT) with urine NAG and
      GGT/creatinine ratios was assessed in dogs with gentamicin-induced
      nephrotoxicosis. Eighteen 6-month-old male Beagles with normal renal function
      were randomly divided into 3 groups of 6. Each group was fed a different
      concentration of protein (high protein, 27.3%; medium protein, 13.7%; and low
      protein, 9.4%) for 21 days. After dietary conditioning, gentamicin was
      administered at a dose of 10 mg/kg IM tid for 8 days and each group was continued
      on its respective diet. Endogenous creatinine clearance and 24-hour urinary
      excretion of NAG and GGT were determined after dietary conditioning (day 0) and
      on days 2, 4, 6, and 8 of gentamicin administration. In addition, urine NAG and
      GGT/creatinine ratios (IU/L divided by mg/dL) were determined from catheterized
      spot urine samples obtained between 7 and 10 AM on the same days. The correlation
      between 24-hour urinary enzyme excretion and urine enzyme/creatinine ratio in the
      spot urine samples was evaluated by simple linear regression analysis. Spot
      sample urine enzyme/creatinine ratios were significantly correlated with 24-hour
      urinary enzyme excretion through day 4 for dogs on low dietary protein, through
      day 6 for those on medium protein, and through day 8 for those on high dietary
      protein. Mean +/- SD baseline values for urine NAG/creatinine ratio and 24-hour
      urinary NAG excretion were 0.06 +/- 0.04 and 0.19 +/- 0.14 IU/kg/24 hr,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531178
TI  - Activation of the renin-angiotensin system in dogs with asymptomatic and mildly
      symptomatic mitral valvular insufficiency.
AB  - The renin-angiotensin system has important pathophysiologic implications in the
      development of congestive heart failure. The activity of the renin-angiotensin
      system early in the course of heart disease and heart failure in dogs was
      evaluated by measuring the plasma renin activity (PRA) and plasma aldosterone
      concentration (PAC) in 18 Cavalier King Charles Spaniels with asymptomatic or
      mildly symptomatic mitral valvular insufficiency, and in 18 healthy Cavalier King
      Charles Spaniels. All dogs were unmedicated and had no other diseases. The PRA
      was high in the dogs with mitral valvular insufficiency (median 3.44 ng/mL/h,
      interquartile interval 2.59 to 8.66 ng/mL/h) compared with the controls (median
      2.51 ng/mL/h, interquartile interval 1.44 to 3.58 ng/mL/h). The PAC was also
      higher in the dogs with mitral insufficiency (median 53 pg/mL, interquartile
      interval 33 to 138 pg/mL) than in the control group (median 27 pg/mL,
      interquartile interval 11.5 to 54 pg/mL). However, there was considerable overlap
      between the 2 groups in both PRA and PAC. It was concluded from these data that
      there is early activation of the renin-angiotensin system in some Cavalier King
      Charles Spaniels with mitral valvular insufficiency. Further prospective studies
      are needed to determine if early intervention with angiotensin-converting enzyme
      inhibitors will be valuable in this group of patients.

PMID- 8531179
TI  - Endoscopically guided balloon dilatation of benign esophageal strictures in 6
      cats and 7 dogs.
AB  - Benign esophageal strictures in 6 cats and 7 dogs were treated with
      endoscopically guided balloon dilatation. Six of 13 had a history of anesthesia
      within 3 weeks prior to the onset of signs; 8 animals had a single stricture, and
      5 had multiple strictures, for a total of 19 strictures. Four of the 19
      strictures were in the upper esophagus, 11 were in the middle esophagus, and 4
      were in the lower esophagus. The luminal diameters ranged from 1 to 18 mm, with a
      mean of 5.1 mm. Twelve animals survived the immediate postprocedure period and
      had a total of 50 dilatation procedures performed; the mean number of procedures
      per animal was 4.2 (range, 2 to 8). Complications included mild bleeding and
      tearing (11 of 13), moderate bleeding (1 of 13), and esophageal perforation (1 of
      13). The cat with the perforation was subsequently euthanized. Follow-up
      information was available on the 12 remaining animals; 9 were known to be alive 6
      to 59 months (mean, 28.2 months) after dilatation. Two were euthanized, 1 for
      persistence of signs and the other for unrelated causes. One animal died of
      possible aspiration pneumonia. Three of 13 animals had complete and 9 had partial
      resolution of signs. Of the 9 animals with partial resolution, 7 were
      substantially better with dietary modification, 1 was moderately better, and 1
      had minimal improvement. Eleven of 13 animals (85%) had a successful outcome with
      moderate to complete resolution of signs. Thus, it is concluded that
      endoscopically guided balloon dilatation is an effective and relatively safe
      treatment for benign esophageal strictures in dogs and cats.

PMID- 8531180
TI  - An echocardiographic study of atrial fibrillation in horses: before and after
      conversion to sinus rhythm.
AB  - Two-dimensional and M-mode echocardiograms were recorded from 41 horses before
      they were successfully treated for atrial fibrillation. In addition, these
      examinations were performed in a subgroup of 20 horses after treatment, and the
      results were compared with pretreatment values. Atrial fibrillation in this group
      of horses was associated with a reduction of mean left ventricular fractional
      shortening (mean 31% +/- 5.24%), and 22 of the 41 horses were below the reference
      range. The remaining mean M-mode variables were within the normal reference
      range, although 12 horses had increased left ventricular lumen dimensions in
      systole, and 8 horses had decreased left ventricular ejection times. Abnormal
      motion of the mitral valve was present in all horses and was characterized by the
      absence of A peaks, which were replaced by small diastolic undulations in 55% of
      the horses. In horses 1 to 20, after conversion to sinus rhythm, the mean
      fractional shortening increased (35.34% +/- 5.4%, P = .004), but there were no
      significant differences in heart rate or left ventricular lumen diameters in
      systole or diastole. These results suggest that ventricular function may be
      compromised by the presence of atrial fibrillation. However, this improved after
      correction of the arrhythmia.

PMID- 8531181
TI  - Echocardiographic detection of flail left atrioventricular valve cusp from
      ruptured chordae tendineae in 4 dogs.
AB  - Echocardiography was used to identify a flail left atrioventricular valve cusp
      caused by ruptured chordae tendineae in each of 4 dogs; two-dimensional
      echocardiography was superior to M-mode echocardiography in identifying the flail
      cusps. The following findings on two-dimensional imaging were characteristic: the
      tip of the flail cusp extended beyond the line of left atrioventricular valve
      cusp closure and pointed toward the left atrium in systole; the tip was thrust
      into the left ventricle, and then toward the left ventricular outflow tract in
      diastole, forming a convex surface to the cusp, which faced toward the left
      ventricle. The flail motion of the left atrioventricular valve cusp was best
      observed in the right parasternal long axis or left apical four-chamber views, in
      a plane parallel to the long axis of the left ventricle and left atrium. Rupture
      of chordae tendineae leading to flail cusp was attributed to chronic valve
      degeneration (endocardiosis) in all 4 dogs. Echocardiographic or clinical
      diagnoses were confirmed by postmortem gross and microscopic studies in all dogs.

PMID- 8531182
TI  - Indwelling cecal catheters for fluid administration in ponies.
AB  - Two different fluid solutions were infused through percutaneous cecal catheters
      in 6 healthy ponies to determine the effects on body weight; CBC; packed cell
      volume (PCV); total plasma protein concentration; plasma fibrinogen
      concentration; abdominal fluid analysis; concentrations of blood urea nitrogen
      (BUN), serum creatinine, Ca, total CO2 (TCO2), Na, Cl, K, and P; and fractional
      clearance (FC) of Na, Cl, K, and P. During intracecal administration of solution
      1, FCNa and FCCl were significantly increased, whereas FCK and BUN were
      significantly decreased. During administration of solution 2, FCNa and serum P
      were significantly increased, while PCV was significantly decreased. All ponies
      developed peritonitis during the study. Complications included catheter-related
      problems, diarrhea, laminitis, and hypocalcemia. We concluded that hydration and
      electrolyte balance could be maintained by administration of crystalloid
      solutions intracecally, but that complications were associated with the
      procedure.

PMID- 8531183
TI  - A portable blood gas analyzer for equine venous blood.
AB  - Evaluation of a portable blood gas analyzer, (StatPal II, Unifet, Inc, La Jolla,
      CA) was performed using tonometered solutions and equine blood. Samples were
      analyzed by the StatPal II and either an Instrument Laboratory IL1306 (Lexington,
      MA) or a Radiometer ABL50 blood gas analyzer (Radiometer America Inc., Westlake,
      OH). Comparison of the StatPal II and the IL1306 was done by analysis of 3
      tonometered solutions (acidic, normal, and alkalotic) and 27 equine venous blood
      samples. Blood pH, PCO2, PO2, and [HCO3] values were altered by IV infusion of 5%
      sodium bicarbonate or exercising the horses on a treadmill. Comparison of the
      StatPal II and the Radiometer was performed by analysis of 78 blood samples
      collected from Standardbred horses before a race. Data were analyzed for the
      venous blood samples using a paired two-tailed Student's t test and Bland-Altman
      plots, with significance set at P < .05. The coefficients of variation for pH,
      Pco2, Po2, and [HCO3-] values of the tonometered solutions analyzed by the
      StatPal II ranged from 0.067% to 0.087%, 2% to 3.21%, 1.21% to 2.67%, and 0.267%
      to 0.828%, respectively. Comparison of the equine blood samples analyzed by the
      StatPal II and the IL1306 demonstrated statistically significant, but clinically
      irrelevant differences in pH, Pco2, and Po2, but not [HCO3-]. There were
      statistically significant, but clinically irrelevant differences between the
      StatPal II and the Radiometer for pH, Pco2, and [HCO3-], but not for Po2. It is
      concluded that the StatPal II provides reproducible and acceptable analysis of
      equine venous blood gas samples.

PMID- 8531184
TI  - Monoclonal gammopathy in a dog with chronic pyoderma.
AB  - A monoclonal gammopathy composed of immunoglobulin G, with concurrent light-chain
      proteinuria and generalized lymph node plasmacytosis, was associated with chronic
      pyoderma in a dog. A uniform population of plasma cells was observed
      cytologically and histologically in multiple lymph node specimens. A diagnosis of
      monoclonal gammopathy of unknown significance was eventually made by exclusion of
      other known causes of monoclonal gammopathy, resolution after antibiotic therapy,
      and no evidence of lymphoproliferative disease after 11 months of follow-up and
      subsequent necropsy. This report expands the diagnostic considerations for
      monoclonal gammopathies in the dog.

PMID- 8531185
TI  - Central diabetes insipidus in a dog with a pro-opiomelanocortin-producing
      pituitary tumor not causing hyperadrenocorticism.
AB  - Central diabetes insipidus was diagnosed by vasopressin measurements during
      hypertonic stimulation in a 9-year-old male giant Schnauzer with polyuria and
      polydipsia. The impaired release of vasopressin was believed to be caused by a
      large pituitary tumor, which was visualized by computed tomography. Studies of
      the function of the anterior lobe and the pars intermedia of the pituitary gland
      were conducted, and high concentrations of ACTH and alpha-melanotrophic hormone
      (alpha-MSH) were found without concomitant hyperadrenocorticism. Studies of the
      molecular size of the immunoreactive ACTH in plasma by gel filtration revealed
      that most of the circulating immunoreactivity was not ACTH but its precursor pro
      opiomelanocortin (POMC) and low-molecular-weight POMC-derived peptides. The
      pituitary tumor of this dog probably originated from melanotrophic cells of the
      pars intermedia. The sensitivity of the pituitary-adrenocortical system for the
      suppressive effect of dexamethasone was unaffected.

PMID- 8531186
TI  - Idiopathic neuromyopathy in a young American cocker spaniel.

PMID- 8531187
TI  - Society for the Study of Fertility and British Neuroendocrine Group joint winter
      meeting. Oxford, December 1995. Abstracts.

PMID- 8531188
TI  - Thymosin alpha-1 and FA-1 monoclonal antibody affect fertilizing capacity of
      human sperm by modulating protein phosphorylation pattern.
AB  - The present investigation was conducted to investigate the modulation of
      phosphorylation pattern of human sperm membrane proteins during capacitation by
      thymosin alpha-1 (T alpha 1) (which enhanced sperm penetration index) and anti-FA
      1 monoclonal antibody (anti-FA-1 mAb) (which completely blocked sperm
      penetration) using 32P metabolic labeling, in vitro kinase assay and Western
      immunoblot analysis. In 32P metabolic labeling experiments, T alpha 1 (0.25 and
      0.5 microgram/100 microliters) enhanced phosphorylation of 7 proteins in four
      molecular regions namely one protein (190 kDa) in 200-kDa, two proteins (112 and
      104 kDa) in 97-kDa, two proteins (48 and 42 kDa) in 43-kDa and two proteins (31
      and 25 kDa) in 29-kDa molecular regions, respectively. Anti-FA-1 mAb (10
      micrograms/100 microliters) resulted in a general decrease in the 32P labeling of
      these sperm proteins. In in vitro kinase assay using non-capacitated sperm
      extracts, T alpha 1 (0.5 microgram/100 microliters) enhanced autophosphorylation
      of 14 proteins in various molecular regions (122, 105, 95, 89, 73, 62, 48, 46,
      40, 33, 30, 28, 25 and 22 kDa, respectively). The same concentration of T alpha 1
      did not affect autophosphorylation of proteins in capacitated sperm extract. Anti
      FA-1 mAb (10 micrograms/100 microliters) inhibited autophosphorylation of a
      subset of 8 proteins (122, 104, 95, 89, 73, 62, 48 and 46 kDa, respectively) in
      non-capacitated sperm membrane extracts, and 12 proteins (112, 104, 95, 89, 73,
      62, 48, 46, 33, 30, 28 and 25 kDa, respectively) in capacitated sperm membrane
      extracts. In the Western immunoblot analysis, T alpha 1 resulted in a
      concentration-dependent increase in tyrosine phosphorylation of two proteins (95
      and 51 kDa) during capacitation of human sperm, whereas anti-FA-1 mAb inhibited
      tyrosine phosphorylation of both proteins. These results indicate that T alpha 1
      and anti-FA-1 mAb affect the fertilizing capacity of human sperm by modulating
      phosphorylation of proteins especially tyrosine phosphorylation of 95- and 51-kDa
      proteins during capacitation. These findings also suggest that there may be a
      signal transduction pathway(s) involved in phosphorylation of membrane proteins
      during capacitation and that an exogenous stimulus affecting a single membrane
      protein component can modulate phosphorylation of all the relevant proteins
      involved in capacitation/acrosome reaction of human sperm.

PMID- 8531189
TI  - Fertilization antigen (FA-1) completely blocks human sperm binding to human zona
      pellucida: FA-1 antigen may be a sperm receptor for zona pellucida in humans.
AB  - The effects of purified human sperm fertilization antigen-1 (FA-1), affinity
      purified monoclonal Fab' antibody to FA-1, and monoclonal Fab' antibody to
      phosphotyrosine residues on human sperm-zona interaction were investigated. The
      purified FA-1 antigen completely blocked sperm binding to zona pellucida (P <
      0.0001). Also, the monoclonal Fab' antibodies to FA-1 antigen and phosphotyrosine
      residues significantly (P < 0.05) reduced sperm-zona pellucidae and the
      antibodies were preincubated with sperm before insemination and not vice versa.
      These results suggest that the tyrosine phosphorylation especially of FA-1
      antigen has an important role in zona pellucida receptor recognition and binding.
      These findings also suggest that FA-1 antigen may be the sperm receptor involved
      in zona pellucida binding in humans.

PMID- 8531190
TI  - Potential contraceptive use of epididymal proteins: evidence for the
      participation of specific antibodies against rat epididymal protein DE in male
      and female fertility inhibition.
AB  - Previous studies in our laboratory indicated that immunization of male and female
      Wistar and Lewis rats with epididymal protein DE, resulted in the development of
      anti-DE antibodies in over 90% of the animals, with a significant and reversible
      reduction of fertility. In the present study, ELISA assays performed to analyze
      the evolution of the immune response indicated that antibody levels in the sera
      of immunized animals reached a maximum at 8 weeks after the initial injection and
      then gradually decreased, returning to control values by the end of the sixth
      month. Western blot experiments demonstrated that the immune sera specifically
      recognized DE in epididymal sperm extracts and epididymal cytosol, while no
      reaction was observed with different reproductive and essential organs. The
      immune sera were also capable of recognizing DE on the surface of both fresh and
      capacitated sperm as indicated by indirect immunofluorescence experiments.
      Finally, the exposure of sperm to immune sera prior to uterine insemination
      resulted in a significant (P < 0.05) reduction in the percentage of fertilized
      eggs compared to controls, with no effect on sperm motility and viability, nor on
      their ability to undergo capacitation. Together, these results support the
      participation of the raised antibodies as mediators of the antifertility effect
      and suggest a specific interference at the sperm-egg interaction level.

PMID- 8531191
TI  - Immunosuppressive activity of a porcine high-molecular weight uterine
      macromolecule is associated with transforming growth factor-beta.
AB  - A > or = 230 kDa lymphocyte suppressor component recovered from uterine luminal
      protein (ULP) secretions of Landrace and Yorkshire gilts on day 15 of pregnancy
      was further purified by anion-exchange (DEAE Sepharose CL-6B) and gel filtration
      (Sepharose CL-6B) chromatography. Macromolecules within each peak fraction were
      tested for suppression of thymidine (TdR) incorporation into phytohemagglutinin
      (PHA)-treated peripheral blood lymphocytes (PBL). A neutralizing antibody to
      transforming growth factor-beta (TGF-beta) was added to additional cultures in
      order to determine whether suppressor activity of high-molecular weight
      macromolecules was associated with TGF-beta. The > or = 230 kDa component
      suppressed (P < 0.0005) TdR incorporation into PHA-treated PBL and anti-TGF-beta
      reversed (P < 0.034) the suppressor response. Following anion-exchange
      chromatography of this component, suppressor activity was greatest (P < 0.05) for
      an acidic component (fraction III), which comprised 45.9% of eluted
      macromolecules. Sepharose CL-6B chromatography of fraction III resulted in a
      major (58.7% of eluted macromolecules) component (> or = 4 x 10(6) Da (> or = 4
      MDa), eluted at the void volume) which suppressed (P < 0.05) TdR incorporation
      into PHA-treated PBL. Anti-TGF-beta reduced the suppressor activity of this
      macromolecule by 34.2%. Suppressor responses were not associated with viabilities
      of PBL. These data demonstrate that ULP secretions from gilts on day 15 of
      pregnancy contain a > or = 4 MDa macromolecule which suppresses proliferative
      responses of PBL and likely serves as a carrier for TGF-beta.

PMID- 8531192
TI  - IgM class autoantibodies in human cord serum.
AB  - It has previously been shown that human neonatal B lymphocytes in vitro can
      synthesize autoantibodies which typically are of IgM class, polyreactive and of
      low affinity and thought to represent natural autoantibodies. We screened 1034
      cord serum specimens to find sera with elevated IgM levels; 98 such sera were
      further examined by an enzyme-linked immunosorbent assay (ELISA) to determine
      whether antibodies against a panel of autoantigens could be found. We detected
      low levels of IgM class antibodies against cardiolipin, pyruvate dehydrogenase,
      single-stranded DNA, thyroglobulin and Fc fragments of IgG as rheumatoid factors.
      The IgM concentration correlated with autoantibody levels. The specificity of the
      autoantibody assays was confirmed by inhibition tests. We conclude that several
      types of autoantibodies can be found in some sera of newborns and that increased
      IgM concentration of some neonates may reflect a polyclonal antibody response.

PMID- 8531193
TI  - Tumor necrosis factor-alpha affects in vitro hormone production by JEG-3
      choriocarcinoma cell cultures.
AB  - Steroid hormones, produced by the placenta, appear to be critically important in
      maintaining the pregnancy of experimental animals and possibly humans. Previous
      studies in our laboratory have shown that macrophage-conditioned media, which are
      known to contain several cytokines including tumor necrosis factor-alpha (TNF
      alpha), decreased the in vitro synthesis of progesterone (P) and increased the
      synthesis of estradiol (E2) by placental fragments. The present study was
      designed to further our understanding of the effect of cytokines on the synthesis
      of placental trophoblast hormones. The current study shows that TNF-alpha (1-20
      ng/ml) decreases the in vitro synthesis of P and increases the synthesis of both
      E2 and human chorionic gonadotropin (hCG) by JEG-3 choriocarcinoma cells (a model
      for trophoblast hormone synthesis). The effects of TNF-alpha are independent of
      changes in formation of adenosine 3':5' cyclic-monophosphate, guanosine 3':5'
      cyclic-monophosphate, prostaglandin E2, and prostaglandin F2 alpha. However, the
      effect of TNF-alpha on P formation is blocked by cycloheximide (1 microgram/ml).
      These observations suggest TNF-alpha could have effects on placental hormone
      synthesis which might be important in the pathogenesis of both normal and preterm
      labor. At least some of these effects appear mediated through new protein
      synthesis.

PMID- 8531194
TI  - Response to Leydig cell apoptosis in the absence of testicular macrophages.
AB  - Removal of apoptotic cells from the tissues appears to be a major function of
      resident tissue macrophages. In order to investigate further the role of
      testicular macrophages after massive Leydig cell death, adult rats were injected
      intra-testicularly with liposome-entrapped dichloromethylene diphosphonate
      (Cl2MDP-lp, right testis) to deplete testicular macrophages, and with NaCl (left
      testis) as control. Ten days later, the animals were injected intraperitoneally
      with ethylene dimethane sulphonate (EDS) to induce Leydig cell apoptosis. In
      macrophage-containing testes there was a 2-fold increase in the number of
      macrophages on days 1-3 after EDS treatment and Leydig cells were completely
      eliminated from the interstitium by the second day after treatment. The main
      differences in the response to Leydig cell death in macrophage-depleted testes
      were: (1) an early rise in the concentration of small mononuclear, lymphocyte
      like cells, (2) a greater influx of circulating monocytes, (3) the existence of
      variable inflammatory infiltrates on days 3-4, and (4) the disappearance of
      infiltrating monocytes by day 10. These results suggest that resident macrophages
      prevent the inflammatory reaction elicited by massive Leydig cell death.

PMID- 8531196
TI  - The sodium concentration of lateral intercellular spaces.

PMID- 8531195
TI  - Sodium current inhibition by internal calcium: a combination of open-channel
      block and surface charge screening?
AB  - Internal application of millimolar concentrations of calcium to batrachotoxin
      (BTX)-activated rat skeletal muscle sodium channels, bathed symmetrically in 200
      mM NaCl, causes a reduction in apparent single-channel amplitude without visibly
      increasing noise at a bandwidth of 50 Hz. A greater calcium-induced reduction
      occurred upon removal of external sodium ions. Internal calcium acted similarly
      in high ionic strength solutions (3M NaCl), where surface charges are effectively
      screened, suggesting that calcium acts, in part, by binding within the pore and
      occluding the conducting pathway. In low ionic strength solutions (20 mM NaCl),
      internal addition of N-Methyl-Glucamine (NMG) ions decreased the single channel
      amplitude consistent with screening of negative surface charges. An accurate
      description of the dose dependence of calcium inhibition, using either a simple
      blocking model, or rate theory calculations of ion permeation and block, also
      required surface charge screening. Hence, our data support the view that sodium
      current inhibition by internal calcium arises from a combination of both open
      channel block and surface charge effects.

PMID- 8531197
TI  - Quaternary ammonium ion blockade of IK in nerve axons revisited. Open channel
      block vs. state independent block.
AB  - The mechanism of blockade of the delayed rectifier potassium ion channel in squid
      giant axons by intracellular quaternary ammonium ions (QA) appears to be
      remarkably sensitive to the structure of the blocker. TEA, propyltriethyl
      ammonium (C3), and propyltetraethylammonium (TAA-C3) all fail to alter the
      deactivation, or "tail" current time course following membrane depolarization,
      even with relatively large concentrations of the blockers, whereas
      butyltriethylammonium (C4), butyltetraethylammonium (TAA-C4), and
      pentytriethyammonium (C5) clearly do have such an effect. The relative electrical
      distance of blockade for all of these ions is approximately 0.25-0.3 from the
      inner surface of the membrane. The observations concerning TEA, C3, and TAA-C3
      suggest that these ions can block the channel in either its open or its closed
      state. The results with C4, TAA-C4, and C5 are consistent with the open channel
      block model. Moreover, the sensitivity of block mechanism to the structure of the
      blocker suggests that the gate is located close to the QA ion binding site and
      that TEA, C3, and TAA-C3 do not interfere with channel gating, whereas C4, TAA
      C4, C5, and ions having a longer hydrophobic "tail" than C5 do have such an
      effect. The parameters of block obtained for all QA ions investigated were
      unaffected by changes in the extracellular potassium ion concentration.

PMID- 8531198
TI  - Amino acid current through anion channels in cultured human glial cells.
AB  - During volume regulation in hypotonic media, glial cells release a large portion
      of their amino acids. These amino acid losses appear to be mediated by a
      diffusion type of transport and a swelling-activated chloride channel seems to be
      involved. The objective of this project was to provide direct evidence that amino
      acids could diffuse through a Cl- channel. Using a human glial cell line, Cl-
      currents activated in hypotonic media were measured in whole-cell patch clamp. To
      measure the currents produced by amino acids, it was necessary to increase the pH
      of external solutions to basic values reaching 9.6 and 10.0 to raise the
      concentration of the anionic form of these amino acids. Introducing external
      hypotonic media containing high concentrations of amino acids, like glycine,
      taurine, glutamine and glutamate, it was possible to measure their respective
      current-voltage curves with NMDG-Cl-filled pipettes. From the reversal
      potentials, their permeability ratios with respect to chloride were determined.
      It was found that the low molecular weight amino acids, like glycine, were most
      permeant, while the larger ones, like glutamine, had a lower permeability with
      respect to chloride. The amino acids with two carboxyl groups, like glutamate,
      had a much lower permeability ratio. The reversal potentials for some
      metabolites, like lactate and malate were also measured for comparison. These
      results demonstrate that amino acids can diffuse through anion channels and that
      activation of these channels in pathological conditions could be at least partly
      responsible for the observed increase in external amino acids.

PMID- 8531199
TI  - Sodium channel functioning based on an octagonal structure model.
AB  - The complete amino acid sequence of a sodium channel from squid Loligo bleekeri
      has been deduced by cloning and sequence analysis of the complementary DNA. A
      unique feature of the squid sodium channel is the 1,522 residue sequence,
      approximately three-fourths of those of the rat sodium channels I, II and III. On
      the basis of the sequence, and in comparison with those of vertebrate sodium
      channels, we have proposed a tertiary structure model of the sodium channel where
      the transmembrane segments are octagonally aligned and the four linkers of S5-6
      between segments S5 and S6 play a crucial role in the activation gate, voltage
      sensor and ion selective pore, which can slide, depending on membrane potentials,
      along inner walls consisting of alternating segments S2 and S4. The proposed
      octagonal structure model is contrasted with that of Noda et al. (Nature 320; 188
      192, 1986). The octagonal structure model can explain the gating of activation
      and inactivation, and ion selectivity, as well as the action mechanism of both
      tetrodotoxin (TTX) and alpha-scorpion toxin (ScTX), and can be applied not only
      to the sodium channel, but also to the calcium channel, potassium channel and
      cGMP-gated channel.

PMID- 8531200
TI  - Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle.
AB  - Ca(2+)-dependent inhibition of native and isolated ryanodine receptor (RyR)
      calcium release channels from sheep heart and rabbit skeletal muscle was
      investigated using the lipid bilayer technique. We found that cytoplasmic Ca2+
      inhibited cardiac RyRs with an average Km = 15 mM, skeletal RyRs with Km = 0.7 mM
      and with Hill coefficients of 2 in both isoforms. This is consistent with
      measurements of Ca2+ release from the sarcoplasmic reticulum (SR) in skinned
      fibers and with [3H]-ryanodine binding to SR vesicles, but is contrary to
      previous bilayer studies which were unable to demonstrate Ca(2+)-inhibition in
      cardiac RyRs (Chu, Fill, Stefani & Entman (1993) J. Membrane Biol. 135, 49-59).
      Ryanodine prevented Ca2+ from inhibiting either cardiac or skeletal RyRs. Ca(2+)
      inhibition in cardiac RyRs appeared to be the most fragile characteristic of
      channel function, being irreversibly disrupted by 500 mM Cs+, but not by 500 mM
      K+, in the cis bath or by solublization with the detergent CHAPS. These
      treatments had no effect on channel regulation by AMP-PNP, caffeine, ryanodine,
      ruthenium red, or Ca(2+)-activation. Ca(2+)-inhibition in skeletal RyRs was
      retained in the presence of 500 mM Cs+. Our results provide an explanation for
      previous findings in which cardiac RyRs in bilayers with 250 mM Cs+ in the
      solutions fail to demonstrate Ca(2+)-inhibition, while Ca(2+)-inhibition of Ca2+
      release is observed in vesicle studies where K+ is the major cation. A comparison
      of open and closed probability distributions from individual RyRs suggested that
      the same gating mechanism mediates Ca(2+)-inhibition in skeletal RyRs and cardiac
      RyRs, with different Ca2+ affinities for inhibition. We conclude that differences
      in the Ca(2+)-inhibition in cardiac and skeletal channels depends on their Ca2+
      binding properties.

PMID- 8531201
TI  - Ca(2+)-activated K+ channels of human and rabbit erythrocytes display distinctive
      patterns of inhibition by venom peptide toxins.
AB  - Despite recent progress in the molecular characterization of high-conductance
      Ca(2+)-activated K+ (maxi-K) channels, the molecular identities of intermediate
      conductance Ca(2+)-activated K+ channels, including that of mature erythrocytes,
      remains unknown. We have used various peptide toxins to characterize the
      intermediate conductance Ca(2+)-activated K+ channels (Gardos pathway) of human
      and rabbit red cells. With studies on K+ transport and on binding of 125I
      charybdotoxin (ChTX) and 125I-kaliotoxin (KTX) binding in red cells, we provide
      evidence for the distinct nature of the red cell Gardos channel among described
      Ca(2+)-activated K+ channels based on (i) the characteristic inhibition and
      binding patterns produced by ChTX analogues, iberiotoxin (IbTX) and IbTX-like
      ChTX mutants, and KTX (1-37 and 1-38 variants); (ii) the presence of some
      properties heretofore attributed only to voltage-gated channels, including
      inhibition of K transport by margatoxin (MgTX) and by stichodactyla toxin (StK);
      (iii) and the ability of scyllatoxin (ScyTX) and apamin to displace bound 125I
      charybdotoxin, a novel property for K+ channels. These unusual pharmacological
      characteristics suggest a unique structure for the red cell Gardos channel.

PMID- 8531202
TI  - Extracellular ATP binding proteins as potential receptors in mucociliary
      epithelium: characterization using [32P]3'-O-(4-benzoyl)benzoyl ATP, a
      photoaffinity label.
AB  - 3'-O-(4-benzoyl)benzoyl ATP (BzATP) was used as a photoaffinity analog of ATP to
      label potential ATP receptors in ciliated cells. Like ATP, without
      photoactivation, BzATP stimulated the ciliary beat frequency in tissue culture up
      to threefold. Irradiation of intact cells in the presence of [alpha-32P]BzATP
      followed by SDS-PAGE and autoradiography revealed two labeled proteins with
      molecular masses of 46 and 96 kDa (p46 and p96). Photolabeling of both proteins
      was susceptible to digestion with trypsin, implying that the labeled proteins are
      at least partially exposed on the extracellular surface of the plasma membrane.
      The dependence of 32P incorporation in both proteins on [alpha-32P]BzATP
      concentration was similar. Labeling of p46 but not p96 required Ca2+ or Mg2+.
      Various nucleotides stimulated the ciliary frequency, and inhibited the
      photolabeling of p46 and p96. The rank order of apparent affinity for p46 is: ATP
      approximately equal to ADP > GTP gamma S > ADP beta S, UTP, 2MeSATP, AMP-PNP >
      AMP-PCP > AMP > adenosine; for p96 it is: ADP approximately equal to ADP beta S >
      or = ATP >> AMP-PCP, AMP-PNP > GTP gamma S > or = AMP > 2MeSATP, UTP, adenosine.
      The rank of stimulation of ciliary beat frequency is: ADP beta S, UTP > or =
      2MeSATP, GTP gamma S, AMP-PNP, ATP > or = ADP > AMP-PCP > adenosine > AMP. These
      results suggest the involvement of p46 in the stimulatory effect of extracellular
      ATP on the ciliary beat, as a P2 purinoceptor. On the other hand, p96 may
      represent a P2 purinoceptor or an ectonucleotidase.

PMID- 8531203
TI  - Inhibition of Ca(2+)-dependent Cl- channels from secretory epithelial cells by
      low internal pH.
AB  - The actions of intracellular pH (pHi) on Ca(2+)-dependent Cl- channels were
      studied in secretory epithelial cells derived from human colon carcinoma (T84)
      and in isolated rat parotid acinar cells. Channel currents were measured with the
      whole cell voltage clamp technique with pipette solutions of different pH. Ca(2+)
      dependent Cl- channels were activated by superfusing ionomycin to increase the
      intracellular calcium concentration ([Ca2+]i) or by using pipette solutions with
      buffered Ca2+ levels. Large currents were activated in T84 and parotid cells by
      both methods with pHi levels of 7.3 or 8.3. Little or no Cl- channel current was
      activated with pHi at 6.4. We used on-cell patch clamp methods to investigate the
      actions of low pHi on single Cl- channel current amplitude in T84 cells. Lowering
      the pHi had little or no effect on the current amplitude of a 8 pS Cl- channel,
      but did reduce channel activity. These results suggest that cytosolic
      acidification may be able to modulate stimulus-secretion coupling in fluid
      secreting epithelia by inhibiting the activation of Ca(2+)-activated Cl-
      channels.

PMID- 8531204
TI  - Histological examination of the effects of corticosterone in larvae of the
      western toad, Bufo boreas (Anura: Bufonidae), and the Oriental fire-bellied toad,
      Bombina orientalis (Anura: Discoglossidae).
AB  - The effects of corticosterone (CORT)-treatment on various tissues were examined
      in two species of anuran larvae, the discoglossid Bombina orientalis, and the
      bufonid Bufo boreas. Corticosterone was administered directly into aquarium water
      for 15 days. After treatment, histological analyses were conducted on skin, gut,
      spleen, thymus, and neural and muscle tissue. Corticosterone treatment prevented
      sloughing of the skin, which resulted in a build-up of stratum corneum, and
      inhibited the development of gland nests and the subsequent formation of dermal
      granular and mucous glands in both species. Corticosterone treatment also
      decreased epithelial folding in the gut and caused vesiculation of the gut
      epithelial cells. The thymus of CORT-treated animals was significantly reduced in
      size (P < .05) and cell density (P < .05), and the spleen of CORT-treated animals
      was completely involuted. The brain and pituitary of CORT-treated animals had a
      decreased cell density (P < .05) and many pyknotic cells. An examination of
      muscle revealed that muscle fibers of CORT-treated animals had a decreased cross
      sectional area (P < .05). The dose of CORT used (1.1 microM) was within the range
      used in other studies in the literature and resulted in tissue levels within the
      range experienced by larvae at metamorphic climax. Thus, this study is
      appropriate to address the histological effects of CORT in experimental
      manipulations and the role of increasing CORT at metamorphic climax. The data
      suggest that increasing endogenous CORT at metamorphosis may be involved in
      degeneration of larval tissue, prior to regeneration, which is stimulated by
      thyroid hormones.

PMID- 8531205
TI  - Osmotic compression of skinned cardiac and skeletal muscle bundles: effects on
      force generation, Ca2+ sensitivity and Ca2+ binding.
AB  - Length-dependence of myofilament Ca2+ sensitivity is now considered to be an
      important component of the steep relationship between active force and sarcomere
      length along the ascending limb of the cardiac force-length curve. Studies with
      skinned cardiac muscle preparations have demonstrated that Ca(2+)-troponin C
      affinity is significantly increased as sarcomere length is increased over the
      range 1.7-2.3 microns. Increase in sarcomere length is accompanied by a reduction
      in interfilament spacing. In skinned fiber preparations from both cardiac and
      skeletal muscle osmotic compression of the filament lattice enhances myofilament
      Ca2+ sensitivity. This study was undertaken to evaluate the hypothesis that a
      change in filament separation may contribute to the length-dependent activation
      seen in cardiac muscle. Moderate reduction in interfilament spacing caused by
      exposure to Dextran T-500 (5-10%) produced an increase in force generation in
      both maximally activated and partially activated preparations of skinned bovine
      ventricular muscle. With fiber bundles of mean sarcomere length 1.7 microns the
      addition of 5% Dextran T-500 produced an increase in Ca2+ sensitivity of about
      0.25 pCa units and a significant increase in Ca2+ binding in the pCa range (6.0
      5.0) in which the single regulatory site of cardiac troponin C is titrated. This
      concentration of Dextran T-500 produced a reduction in fiber width equivalent to
      that produced by stretching fibers from sarcomere length 1.7 microns to sarcomere
      length 2.3 microns Osmotic compression of skinned rabbit psoas muscle fibers also
      enhanced Ca2+ sensitivity but there was no significant change in Ca(2+)-troponin
      C affinity. These data suggest that 1) an important component of length-dependent
      Ca2+ sensitivity in both cardiac and skeletal muscle is the change in
      interfilament spacing, and 2) in cardiac muscle a reduction in spacing, like
      increase in length, leads to a specific increase in Ca(2+)-troponin C affinity.
      Thus both filament overlap and filament separation contribute to the length
      dependence of Ca2+ sensitivity and Ca2+ binding in cardiac muscle.

PMID- 8531206
TI  - Maternal consumption of a low vitamin D diet retards metabolic and contractile
      development in the neonatal rat heart.
AB  - During the fetal and suckling periods of mammalian development, the mother serves
      as the sole nutritional source for the offspring. As such, the quality of the
      maternal diet effects growth and development of the offspring during these
      periods. This study sought to determine if a maternal vitamin D deficiency
      altered the well characterized development of the neonatal heart. Weaned rat pups
      (21-day-old) were obtained from mothers who had consumed either a vitamin D
      supplemented diet (3000 IU of vitamin D/kg) or a low vitamin D diet (< 200 IU of
      vitamin D/kg) prior to becoming pregnant and throughout pregnancy and suckling.
      These pups were sacrificed, hearts excised, and the hearts biochemically analysed
      for metabolic and contractile protein properties. The pups of dams fed the low
      vitamin D diet were slightly hypocalcemic relative to those on the supplemented
      diet (2.28 v 2.41 mumol/l, P < 0.05), had significantly lower body weights (43 v
      55 g), heart weights (143 v 174 mg), citrate synthase activity (106 v 147 mumol g
      1 min-1), and 3-hydroxyacyl CoA dehydrogenase activity (59 v 91 mumol g-1 min-1).
      Hexokinase activity (1.98 v 2.02 mumol g-1 min-1), and the distribution of
      cardiac myosin among its three isoforms (> 85% V1), were unaffected by this
      dietary deficiency, however myofibrillar protein content was approximately 15%
      lower in the experimental hearts. These data demonstrate that maternal
      consumption of a low vitamin D diet results in a general but significant slowing
      of neonatal cardiac development.

PMID- 8531207
TI  - Tension-frequency relationships in normal and cardiomyopathic dog and hamster
      myocardium.
AB  - The objective of this study was to evaluate the tension-frequency relationship in
      normal and cardiomyopathic myocardium from one species with a negative or
      biphasic relationship, the hamster, and one with a positive relationship, the
      dog. Left ventricular papillary muscles from 100-day-old normal Syrian and
      cardiomyopathic (CHF-147) hamsters and right ventricular papillary muscles or
      trabeculae from normal mongrel dogs and dog with pacing-induced heart failure
      were used for the study. Stimulation frequency was varied from 1 to 90/min and
      isometric contractions recorded at each frequency prior to and after the addition
      of phenylephrine 10 microM. A tension-frequency relationship at varying
      extracellular calcium concentrations (1.25, 2.5 and 5.0 mM) was also constructed
      in normal hamster myocardium. Ryanodine 1.2 microM was added to a bath with
      normal hamster muscles and a force-frequency relationship constructed prior to
      and after adding phenylephrine 10 microM. A calcium dose-response curve in normal
      and cardiomyopathic dog myocardium was also constructed. Normal and
      cardiomyopathic hamster myocardium had a biphasic tension-frequency relationship
      with the increase in tension during the second phase being greater in normal v
      cardiomyopathic hamster myocardium (0.66 +/- 0.19 v 0.12 +/- 0.03 g/mm2, P <
      0.05). The initial decrease in tension in response to increasing stimulation
      frequency was markedly attenuated in normal hamster myocardium by increasing
      extracellular calcium concentration. Developed tension was eliminated at lower
      stimulation rates by ryanodine such that when developed tension did occur, it
      increased with increasing stimulation rates. The addition of phenylephrine to
      hamster myocardium modified the tension-frequency relationship of both normal and
      cardiomyopathic dog myocardium and their response to phenylephrine were similar.
      In each case, tension increased progressively with increasing stimulation rate.
      Although the absolute increase in tension caused by increasing extracellular
      calcium was less in cardiomyopathic dog myocardium, the percent increase in
      tension and shortening was greater. We conclude that the tension-frequency
      relationship of normal and cardiomyopathic hamster myocardium are biphasic, with
      the initial negative phase being the result of limitations of sarcoplasmic
      reticulum calcium handling. Phenylephrine modifies this relationship to a
      uniphasic positive one, likely by its effects on both the sarcolemma and the
      sarcoplasmic reticulum. Also, the tension-frequency relationship of normal and
      cardiomyopathic dog myocardium are similar and unmodified by phenylephrine.

PMID- 8531208
TI  - The effect of hypercholesterolemia on the sodium inward currents in cardiac
      myocyte.
AB  - To determine whether chronic hypercholesterolemia affects sodium inward currents
      in cardiac myocytes, whole-cell clamp recordings were made in single cardiac
      myocytes isolated from normo- and hypercholesterolemic rabbits. Modification of
      the serum cholesterol was accomplished by feeding ten 3-month-old male New
      Zealand white rabbits with control diet (group I) and ten with 0.5% cholesterol
      enriched diet (group II), for 3 months. The serum cholesterol levels of group II
      were much higher than those of group I (2042 +/- 231 v 82 +/- 9 mg/dl, P <
      0.001). The cholesterol-ester and free cholesterol component of cardiac
      sarcolemma of group II were also significantly higher than those of group I (26.6
      +/- 12.4 v 10.8 +/- 4.5 nmole/dl, P < 0.001, and 50.9 +/- 14.8 v 27.5 +/- 6.2
      nmole/dl, P < 0.001, respectively). The cell capacitance of hyperlipidemic
      myocytes seemed larger than that of normolipidemic ones (157.4 +/- 6.4 pF v 103.6
      +/- 3.0 pF, P < 0.05). However, the sodium current density on
      hypercholesterolemic ventricular sarcolemma was significantly lower than that of
      normolipidemic sarcolemma. This effect was associated with a leftward shift in
      the inactivation potential and a slowing of the time course of recovery. In
      conclusion, hypercholesterolemia has important effects on the sodium inward
      currents in ventricular myocytes, which may be due to a decrease in current
      density and an alteration in channel functional state.

PMID- 8531209
TI  - L-type Ca channel block by highly hydrophilic dihydropyridines in single
      ventricular cells of guinea-pig hearts.
AB  - Blocking of L-type Ca channels by highly hydrophilic dihydropyridines, NKY-722
      and KV-1360, was investigated in single ventricular cells of guinea-pig hearts
      using the whole-cell voltage clamp technique. At a holding potential of -30 mV,
      NKY-722 (1-100 nM) decreased the amplitude of the L-type Ca channel current (ICa)
      in a concentration-dependent manner. NKY-722 did not change the time constants of
      the decay of ICa. In the presence of NKY-722 (1 microM), the steady-state
      inactivation curve was shifted toward a more negative potential (by -33.0 +/- 2.0
      mV) without changing its slope factor. The use-dependent block was elicited at a
      pulse frequency of 3.3 Hz or more. Even after washing out the drug at -80 mV for
      20 min, ICa inhibited by NKY-722 (100 nM) at -30 mV was scarcely recovered when
      the membrane potential was clamped back to -30 mV. A permanently charged compound
      KV-1360 (0.1-1 microM), a quaternary amine derivative of NKY-722, hardly affected
      ICa by intracellular and extracellular application. These results suggest that,
      in spite of the high degree of ionization (91% in the charged form at pH 7.4),
      the mode of the L-type Ca channel block by NKY-722 is quite similar to that by
      lipophilic dihydropyridines. Consequently, the neutral form of NKY-722 is the
      active compound and this reaches the dihydropyridine receptor by "membranous
      approach".

PMID- 8531210
TI  - Regulation of collagen degradation in the rat myocardium after infarction.
AB  - Fibrillar collagens, essential for maintaining the structural integrity of the
      myocardium, are degraded by matrix metalloproteinase (MMP-1). In other tissues
      collagenolysis is an important component of wound healing. Here we examined
      collagen degradation in the myocardium after infarction. Collagenase activity,
      measured by zymography, and expression of matrix metalloproteinase (MMP-1) and
      tissue inhibitor of metalloproteinase (TIMP) mRNA, detected by Northern blotting
      and in situ hybridization, in the rat heart 6 h to 28 days after left coronary
      artery ligation were studied. Sham-operated rats served as controls. Infarcted
      left ventricle was compared to non-infarcted right ventricle and interventricular
      septum and to sham-operated tissues. We found a transient increase in collagenase
      activity in the infarcted left ventricle, which began at day 2 (4.5-fold increase
      compared to controls), peaked at day seven (6.5-fold increase) and declined
      thereafter, together with a concomitant increase and contribution in
      collagenolytic activity of gelatinases (MMP-2 and MMP-9). An increase in
      collagenase mRNA was not seen until day 7 and only in the infarcted ventricle,
      while changes in MMP-1 activity or mRNA expression were not observed at remote
      sites or in sham-operated controls. Transcription of TIMP mRNA was observed at 6
      h (two-fold increase) in the infarcted ventricle, peaked on day two after MI
      (eight-fold increase) and slowly decreased thereafter. No change in TIMP mRNA
      expression was observed at remote sites or in sham-operated controls. Cells
      responsible for transcription of MMP-1 and TIMP mRNA were fibroblast-like cells,
      not inflammatory or endothelial cells. At the site of infarction post
      translational activation of latent collagenase (MMP-1) plays a greater role in
      the wound healing response than transcription of collagenase mRNA. Collagenase
      mRNA is synthesized when the latent extracellular pool of MMP-1 is reduced
      through the activation of latent collagenases and gelatinases. TIMP mRNA
      synthesis is regulated by the activation of MMPs with the balance between
      collagenase activation and TIMP inhibition determining the amount of
      collagenolysis in infarcted tissue.

PMID- 8531211
TI  - Endothelial cell "swelling" in ischaemia and reperfusion.
AB  - The endothelial cells of cardiac capillaries have been reported to swell as a
      result of ischaemia and reperfusion although there has not previously been any
      attempt to quantify this observation. Whole capillary and luminal cross-sectional
      areas, abluminal and luminal membrane lengths were measured from electron
      micrographs of isolated rat hearts subjected to 30 or 60 min of global ischaemia
      both with and without subsequent reperfusion for 15 min. All the experimental
      protocols resulted in capillaries which appeared swollen by electron microscopy.
      Measurements, however, showed that, after 30 and 60 min ischaemia, this
      appearance was brought about by a decrease in both whole capillary and luminal
      area causing an increase in the distance between abluminal and luminal membranes
      without any change in the endothelial cell cross-sectional area. Reperfusion
      after 30 min caused an increase in capillary dimensions to larger than control
      levels. Only after 60 min ischaemia with reperfusion were the cells really
      swollen with an increase in cross-sectional area. We conclude that (1) we may be
      observing capillary constriction and (2) the word "swelling" in this context
      should be used with caution.

PMID- 8531212
TI  - Protection of isolated rat heart against the Ca2+ paradox. Are gap junction
      channels involved?
AB  - Enzyme release from isolated Langendorff-perfused rat hearts was studied under
      various protective conditions against the Ca2+ paradox. In addition sarcosolic
      free cation concentrations and the membrane potential were measured employing ion
      selective microelectrode techniques during Ca(2+)-free perfusion. Low temperature
      (18 degrees C), low pH (6.5 or 6.1), and polyethylene glycol (9%) during Ca(2+)
      free perfusion all protected isolated hearts against the Ca2+ paradox. Protection
      could only be afforded if the protective agent was continuously present from the
      beginning of the Ca(2+)-free perfusion period. A 10 min "normal" Ca(2+)-free pre
      perfusion was sufficient to abolish the protective potency of the subsequent
      perfusion phase in the presence of the protective agent. The gap junction channel
      blocker heptanol (2 mmol/l) markedly decreased enzyme release during re
      perfusion, but did not afford protection. Sarcosolic free cation concentrations
      were measured during Ca(2+)-free acidic perfusion. [Na+]i was markedly increased
      to about 44 mmol/l without predisposing to cell damage under these conditions. A
      marked reduction of cell damage was also afforded under conditions of hypoxia
      during Ca(2+)- and substrate-free perfusion. Acidosis (pHe = 6.5) under these
      conditions prevented a lethal increase of [Ca2+]i (2 mumol/l) and partially
      preserved a negative membrane potential. It is concluded that the predisposition
      to the Ca2+ paradox is produced by a permeabilisation of gap junction channels at
      low [Ca2+]e and that upon re-elevation of [Ca2+]e a serious Ca2+ influx proceeds
      through these leaks.

PMID- 8531213
TI  - Thin filament activation by phalloidin in skinned cardiac muscle.
AB  - Phalloidin binds very tightly and specifically to actin and brings about a marked
      stabilization of the F-actin filament. In this study the effects of phalloidin on
      force generation and Ca2+ sensitivity of skinned bovine ventricular muscle were
      investigated. At all free Ca2+ concentrations addition of phalloidin to activated
      fibers caused an enhancement of active force. At full Ca2+ activation the force
      increase was about 6% and the relative force enhancement became greater as the
      Ca2+ concentration was decreased. Force-pCa plots obtained with fibers pre
      treated with phalloidin showed that phalloidin produced an approximately 0.2 pCa
      unit increase in Ca2+ sensitivity without significant changes in cooperativity of
      activation. These results suggest that interactions between G-actin subunits may
      play an important role in cardiac force development.

PMID- 8531214
TI  - Urokinase plasminogen activator activity is increased in the myocardium during
      coronary artery occlusion.
AB  - We have previously demonstrated that collateral development takes place in a
      swine model of coronary artery occlusion. In this report we have examined the
      effect of coronary artery occlusion on urokinase and tissue plasminogen activator
      activity in the myocardium. Urokinase activity was increased four-fold in the
      ischemic heart compared to sham and unoperated controls. In contrast, the level
      of tissue plasminogen activator activity remained relatively constant. The
      increase in urokinase activity was associated with an upregulation of urokinase
      RNA levels and of the RNAs corresponding to the plasminogen activator inhibitors,
      PAI I and II. Urokinase has been shown to be an important angiogenic protease
      both in vivo and in cultured cells. Its increase during collateral development
      suggests that urokinase may play a role in angiogenesis in the ischemic heart.

PMID- 8531215
TI  - Superiority of acid extractable glycogen for detection of metabolic changes
      during myocardial ischaemia.
AB  - Various methods for extraction and isolation of myocardial glycogen show
      different yields and identify different glycogen subsets. The aim of the present
      study was to identify a glycogen fraction exposed to changes during myocardial
      ischaemia. Endomyocardial biopsies from 10 pigs were sampled before cardioplegia,
      after cardioplegic arrest, and after reperfusion. Glycogen yields were compared
      following five extraction procedures: (1) hot alkaline tissue digestion, (2)
      homogenization in perchloric acid and subsequent determination in homogenate, (3)
      homogenization in perchloric acid and subsequent determination in supernatant,
      (4) homogenization in perchloric acid and subsequent determination in the
      precipitate redissolved in hot alkaline and (5) homogenization in homogenisation
      buffer with lysating capacity. Glycogen was isolated on filter-paper and
      determined enzymatically. Hot alkaline tissue digestion yielded the highest
      glycogen amounts (63.5 +/- 18.3 nmol/mg wet weight). Glycogen yields in
      perchloric homogenate and supernatant were 51%, perchloric precipitate 47%, and
      buffer 30% of these obtained with hot alkaline. Glycogen yields in hot alkaline
      were comparable to the sum of those obtained in perchloric supernatant ("acid
      extractable glycogen") and redissolved precipitate ("heavily extracted glycogen")
      confirming that glycogen yields obtained with hot alkaline digestion represent
      "total glycogen". Acid extractable glycogen showed superior analytical
      characteristics compared with the other methods. Acid extractable glycogen
      demonstrated a consistent decrease during ischaemia whereas total glycogen and
      glycogen extracted in homogenization buffer tended to decrease. Glycogen in
      perchloric precipitate remained unchanged during ischaemia. These findings
      support a revival of the concept that tissue contains two forms of glycogen.
      Decreases in myocardial glycogen content during myocardial ischaemia are best
      observed with acid extractable glycogen.

PMID- 8531216
TI  - Myocyte electrophysiological properties following the development of
      supraventricular tachycardia-induced cardiomyopathy.
AB  - Chronic supraventricular tachycardia (SVT) causes left ventricular (LV)
      dilatation and dysfunction, diminished myocyte contractile function, and
      abnormalities in sarcolemmal receptor systems. We hypothesized that changes in
      myocyte action potential characteristics and L-type Ca2+ channel (Ca2+ channel)
      function, which are major determinants of myocyte contractile processes, would
      occur with SVT cardiomyopathy. LV function and isolated myocyte contractile
      function were examined in 11 pigs with SVT cardiomyopathy (pace 240 bpm; 3 weeks)
      and 11 control pigs. With chronic SVT, LV fractional shortening fell and myocyte
      shortening velocity was reduced compared to controls (11 +/- 2 v 37 +/- 2%, P <
      0.0001; and 32.5 +/- 1.2 v 55.7 +/- 1.6 microns/s, P < 0.0001, respectively).
      Isolated myocyte action potential upstroke velocity and amplitude were reduced
      with SVT cardiomyopathy compared to controls (92.8 +/- 4.8 v 129.5 +/- 3.1 V/s, P
      < 0.0001; and 98.2 +/- 2.2 v 110.3 +/- 1.3 mV, P < 0.0001, respectively). the
      duration of the myocyte action potential, defined as the time to 90%
      repolarization, was prolonged with SVT cardiomyopathy compared to controls (201.7
      +/- 5.9 v 169.1 +/- 6.8 ms, P = 0.002). These specific abnormalities in the
      indices of myocyte contractile function and action potential characteristics
      which occurred with SVT cardiomyopathy were not normalized following beta
      adrenergic receptor stimulation. In order to determine a potential mechanism for
      the changes in myocyte contractile function and action potential characteristics
      with SVT cardiomyopathy, Ca2+ channel function was examined in control and SVT
      myocytes. In SVT myocytes, peak L-type Ca2+ current (ICa) normalized to membrane
      capacitance and the Ca2+ channel inactivation time constant were reduced compared
      to controls (-2.30 +/- 0.24 v -3.79 +/- 0.28 pA/pF, P = 0.0001; and 104.0 +/-
      10.8 v 199.9 +/- 27.4 ms, P = 0.005, respectively). The abnormalities in Ca2+
      channel function with SVT cardiomyopathy persisted in myocytes with equivalent
      membrane capacitances and were not normalized with beta-adrenergic receptor
      stimulation. In conclusion, findings from the present study suggest that
      fundamental abnormalities in myocyte electrical events (action potential) and
      ionic flux (Ca2+ channel function) are contributory mechanisms for the depressed
      myocyte contractile function with SVT cardiomyopathy.

PMID- 8531217
TI  - Preconditioning in isolated superfused human muscle.
AB  - Studies in isolated superfused rabbit papillary muscles indicate that
      preconditioning (PC) is not confined to arterially perfused myocardium. In the
      present study PC of isolated human right atrial trabeculae was investigated
      avoiding the problems of invasive experimentation in patients. Atrial trabeculae
      were suspended in an organ bath, superfused with Tyrode's solution and field
      stimulated at 1 Hz. After stabilization, muscles were randomly allocated to five
      groups (n = 8 per group). Control (C) muscles had no additional treatment. PC was
      induced by 3 min rapid pacing at 3 Hz with hypoxic substrate-free buffer,
      followed by reoxygenation with substrate for 12 min. In two additional groups 8-p
      sulfophenyltheophylline (SPT) was added to the superfusate either during
      stabilization in controls (C+SPT) or during preconditioning (PC+SPT). In the
      final group, R-phenyl-isopropyl adenosine (R-PIA) was added to the superfusate
      for 5 min to see whether or not this could substitute for preconditioning. All
      muscles were then exposed to 90 min hypoxia with no substrate and pacing at 3 Hz,
      followed by 120 min reoxygenation at 1 Hz. Recovery of developed tension was
      significantly improved by PC 46.5 +/- 2.4% v 24.6 +/- 2.3% in controls) and this
      protective effect was blocked by the addition of SPT without adversely affecting
      controls (recovery in PC+SPT, 25.8 +/- 4.1% and C+SPT, 22.7 +/- 2.9%). R-PIA
      protected the muscles to a similar extent as PC (43.8 +/- 1.9%). These data
      provide evidence for the involvement of adenosine in preconditioning in human
      myocardium.

PMID- 8531218
TI  - Excitatory amino acid receptors in glia: different subtypes for distinct
      functions?
AB  - It is now well established that expression of voltage- and ligand-gated ionic
      channels, as well as G protein-coupled receptors, is not a property unique to
      neurons, but is also shared by macroglial cells (astrocytes and
      oligodendrocytes). These glial cells can receive a variety of signals from
      neurons at different stages of their development. Activation of membrane
      receptors may affect glial cell activity, proliferation, maturation, and survival
      through a complex cascade of intracellular events leading to long-term changes in
      glial cell phenotype and functional organization. Here we review the experimental
      evidence for glutamate receptor expression in glial cells in culture and in situ,
      and the molecular and functional properties of these receptors. We also describe
      some experimental models that identify possible functions of glutamate receptors
      in glia. Now that the existence of glutamate receptors in glia has been
      unambiguously demonstrated, future research will have to 1) determine which
      receptor subtypes are expressed in macroglial cells in vivo; 2) analyze, in
      adequate experimental models, the short- and long-term changes produced by
      glutamate receptor activation in glia; and 3) establish whether these receptors
      play a role in neuron-glia communication in the brain.

PMID- 8531219
TI  - Altered lipid metabolism in the presence and absence of extracellular Ca2+ during
      combined oxygen-glucose deprivation in primary astrocyte cultures.
AB  - The effect of combined oxygen-glucose deprivation (COGD) on lipid metabolism in
      primary rat cortical astrocyte cultures was studied in both the presence and
      absence of extracellular Ca2+. In this study, increases in intracellular Ca2+
      from internal Ca2+ stores were not inhibited nor were internal Ca2+ levels
      buffered. Combined oxygen-glucose deprivation resulted in a quantitative
      reduction in phospholipid levels and an increase in free fatty acid and
      lysophospholipid levels. Four hours after the onset of COGD, ethanolamine- and
      choline glycerophospholipid levels were decreased by 40 and 46% from control
      levels in the presence of Ca2+, respectively. A similar decrease was found 6 hr
      after onset of COGD in the absence of Ca2+. These changes were accompanied by
      elevated levels of the corresponding lysophospholipids. However, the increases in
      lysophospholipid content did not account for the entire loss of ethanolamine- or
      choline glycerophospholipid. Phosphatidylserine was reduced in both the presence
      and absence of extracellular Ca2+ but phosphatidylinositol was only decreased in
      the absence of Ca2+. Statistically significant increases in total fatty acid (FA)
      and polyunsaturated fatty acid (PUFA) levels occurred at 30 min and 3 hr after
      the onset of COGD in the absence and presence of Ca2+, respectively. Arachidonic
      acid levels were increased in both groups by 1 hr. These increases in FA, PUFA,
      and specifically arachidonic acid were time-dependent and increased over the 12
      hr of COGD. Collectively, these results indicate the activation of an
      acylhydrolase mechanism in the possible presence of an inhibited reacylation
      pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531220
TI  - GM1 ganglioside rescues substantia nigra pars compacta neurons and increases
      dopamine synthesis in residual nigrostriatal dopaminergic neurons in MPTP-treated
      mice.
AB  - GM1 ganglioside has been shown to stimulate recovery of the damaged dopamine
      system under a number of different circumstances. In addition to rescue of
      damaged dopamine neurons, the present study assessed the ability of GM1 to
      enhance the synthesis of dopamine in remaining nigrostriatal neurons following 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure. There was a
      significantly greater accumulation of L-dopa 30 min after aromatic amino acid
      decarboxylase inhibition with NSD-1015 (100 mg/kg) and an increase in the ratio
      of L-dopa to dopamine in MPTP+GM1-treated mice than in mice that received only
      MPTP. This effect of GM1 on dopamine synthesis was dependent upon the degree of
      initial damage to the nigrostriatal dopamine system. That is, the GM1 effect on
      dopamine synthesis could not be demonstrated in mice with greater than 95%
      striatal dopamine loss and 75% substantia nigra dopamine neuron loss. These
      results suggest that in addition to previously reported effects of GM1 on rescue
      and repair of dopaminergic neurons, GM1 may also have the ability to enhance
      dopamine synthesis in residual dopaminergic neurons. Direct effects on dopamine
      neurochemistry may contribute to functional improvement seen after GM1 treatment
      in various models of parkinsonism.

PMID- 8531221
TI  - AMPA receptors shape Ca2+ responses in cortical oligodendrocyte progenitors and
      CG-4 cells.
AB  - Intracellular calcium signals triggered by glutamate receptor activation were
      studied in primary cortical oligodendrocyte lineage cells and in the
      oligodendrocyte cell line CG-4. Glutamate, kainate, and AMPA (30-300 microM)
      increased [Ca2+]i in both types of cells at the stage of oligodendrocyte
      progenitors (O-2A; GD3+) or pro-oligodendroblasts (O4+). The peak amplitude of
      Ca2+ responses to glutamate receptor agonists was significantly larger in
      cortical cells. In CG-4 and in cortical cells, the majority (more than 90%) of
      bipolar GD3+ or multipolar O4+ cells responded to kainate. In all the cells
      analyzed, kainate was more efficacious than AMPA and glutamate. The percentage of
      bipolar or multipolar cells responding to glutamate was significantly lower in
      the CG-4 cell line than in primary cultures. Cellular responses typical of
      metabotropic glutamate receptor activation were observed in 20% of the cortical O
      2A progenitors, but in none of the CG-4 cells. The AMPA-selective antagonist GYKI
      52466 blocked kainate-induced Ca2+ responses in cortical O-2A cells. The
      selective AMPA receptor modulator cyclothiazide (30 microM) greatly potentiated
      the effects of AMPA (30-100 microM) on [Ca2+]i in cortical and CG-4 cells. Our
      findings indicate that Ca2+ responses in cells of the oligodendrocyte lineage are
      primarily shaped by functional AMPA receptors.

PMID- 8531222
TI  - Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine
      synthetase (GS) immunoreactions in retinal glia: evidence for coupling of GLAST
      and GS in transmitter clearance.
AB  - Our aim was to identify proteins that mediate the uptake and degradation of
      synaptically released glutamate, focusing on the rat retina with its well-defined
      glutamatergic pathways. Immunoreactivity against the L-glutamate/L-aspartate
      transporter (GLAST) is present in Muller cells. Ultrastructurally, even the
      finest glial processes, particularly those ensheathing identified structures of
      glutamatergic transmission (rod spherules), are immunoreactive for GLAST. Further
      light and electron microscopic observations revealed that also retinal astrocytes
      and pigment epithelial cells are immunoreactive for GLAST. No neuronal or
      microglial staining was observed. This is in line with uptake of exogenous
      [3H]glutamate previously localized specifically in Muller cells and pigment
      epithelium (Ehinger and Falck: Brain Res 33:157-172, 1971). Since endogenous
      glutamate can only be demonstrated in Muller cells if glutamine synthetase (GS)
      is inhibited (Pow and Robinson: Neuroscience 60:355-366, 1994), the
      immunocytochemical localization of GS was determined. GS immunoreactivity was
      found in all but only those cell types immunoreactive for GLAST. The light and
      electron microscopic patterns of immunoreactivity were very similar, particularly
      in the outer plexiform layer. The three cell types containing both GS and GLAST
      (Muller cells, astrocytes, and retinal pigment epithelium) are related
      developmentally. In the light of the two references quoted the present data
      indicate that the proteins mediating retinal uptake and degradation of
      synaptically released glutamate may be GLAST and GS, respectively, and that they
      may operate in concert to terminate the neurotransmitter action of glutamate.

PMID- 8531223
TI  - Expression of neurotrophins in skeletal muscle: quantitative comparison and
      significance for motoneuron survival and maintenance of function.
AB  - Neurotrophins play a crucial role in the regulation of survival and maintenance
      of specific functions of various populations of neurons. Brain-derived
      neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4)
      have been shown to support motoneuron survival during embryonic development and,
      after birth, to protect motoneurons from degeneration after nerve lesion. We have
      compared the levels of these neurotrophins in skeletal muscle by quantitative
      Northern blot analysis, both during embryonic development and postnatally. We
      localized the sites of expression of these neurotrophins by in situ hybridisation
      and analysed the expression of trkB in the spinal cord by in situ hybridisation
      and immunohistochemistry. NT-3 is most abundantly expressed both during embryonic
      development and in the postnatal phase, followed by NT-4. The levels of BDNF are
      very low, in particular after birth. After nerve lesion, NT-3 mRNA essentially
      remained unchanged, whereas NT-4 mRNA rapidly decreased. The slow increase in
      BDNF expression seems to be essentially due to the expression in Schwann cells
      rather than skeletal muscle, demonstrated by in situ hybridisation. Our data
      indicate that motoneurons can receive trophic support from several members of the
      neurotrophin gene family during the period of naturally occurring cell death.
      Postnatally, the predominant ligand acting via trkB on motoneurons is NT-4,
      whereas BDNF expression seems to play a role mainly after nerve lesion.

PMID- 8531224
TI  - Neurotoxicity of the human immunodeficiency virus type 1 tat transactivator to
      PC12 cells requires the Tat amino acid 49-58 basic domain.
AB  - The acquired immunodeficiency syndrome (AIDS) frequently involves the central
      nervous system (CNS) and manifests as dementia due to encephalitis or diffuse
      neurodegeneration. Human immunodeficiency virus type 1 (HIV-1) proteins,
      potentially transported into the CNS by mononuclear inflammatory cells, have been
      implicated in the etiology of this HIV-1 associated neurological dysfunction.
      Here we investigate the neurotoxicity of the essential HIV-1 regulator protein
      Tat in vivo after microinfusion into the rat brain and in vitro using PC12, NG108
      15, and GT17 neuronal cell lines. Infusion of either chemically synthesized Tat
      (Tat86) or recombinant Tat (rTat) into the striatal gray matter in Sprague-Dawley
      rats resulted in postural deviation ipsilateral to the infusion, a clinical
      presentation in rats associated with complete striatal dysfunction. Histologic
      examination 3 days after infusion revealed massive necrosis in the area of the
      distribution of the infusion. Infusion of heat denatured rTat, peptide Tat49-58,
      or peptide Tat57-86 did not result in clinically or histologically detectable
      brain damage. After 3 days incubation in vitro, the lethal dose for half (LD50)
      of PC12 cells due to rTat was 5 micrograms/ml. The LD50 for Tat86 under the same
      conditions was 10 micrograms/ml. Tat49-58 and Tat57-86 peptides were not toxic in
      vitro even at 10-fold higher doses. At 5 micrograms/ml, rTat was toxic to 100% of
      GT17 cells after 24 hr. At 5 micrograms/ml, Tat86 was toxic to 90% of the NG108
      15 cells after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531225
TI  - Localization and partial characterization of a 60 kDa citrulline-containing
      transport form of myelin basic protein from MO3-13 cells and human white matter.
AB  - The localization of myelin basic proteins (MBPs) in an immortalized human-human
      hybrid cell line (MO3-13) formed by fusion of rhabdomyosarcoma TE671-TG6 with
      primary human oligodendrocytes, cultured from surgical specimens, demonstrated an
      intracellular localization in vesicles and vacuoles with an intricate internal
      membranous network and to the external surface of the cell by immunogold electron
      microscopy. The availability of antibodies to one of the components of MBP, i.e.,
      the citrulline containing component ("C-8"), permitted us to localize this
      component of MBP to intracellular vacuoles and also on the external surface of
      the MO3-13 cells. Since the apposition of the external surfaces of the
      oligodendrocyte is responsible for the intraperiod line of the myelin sheath,
      localization of C-8 to the external surface of non-permeabilized cells by
      immunogold scanning electron microscopy is consistent with our observations that
      C-8 is localized to the intraperiod line of myelin (McLaurin et al.: J Neurosci
      Res 35:618-628, 1993). Western blots of isolated MBP from MO3-13 cells, probed
      with an antibody reactive with residues 130-137 of MBP, recognized a protein in
      the 60 kDa range. No immunoreactivity was found in the 18.5 kDa range. This 60
      kDa protein also reacted with a monoclonal antibody raised with residues 70-84 of
      MBP, 2 different polyclonals raised with whole bovine MBP, an antibody to human
      MBP raised in monkeys, and the anti-citrulline antibody. These data strongly
      suggested that the 60 kDa protein contained MBP sequences within its primary
      structure. A similar protein has been isolated from human myelin-containing
      fractions but not from compact myelin demonstrating that the 60 kDa protein from
      MO3-13 cells was not an artefact related to fusion. Sequence determination of
      peptides obtained from enzymic and chemical cleavages revealed that the 60 kDa
      protein contained MBP sequences and peptides with 55-60% homology with dynamin, a
      protein involved in intracellular transport. These data suggest that the
      externalization of MBP in this cell involves transport by fusion of MBP with
      another protein. By sequestering MBP in a larger protein, the possibility of
      inducing autoimmune disease by MBP released, due to cell death, is minimized.

PMID- 8531226
TI  - Increased cyclic AMP in in vitro regenerating frog sciatic nerves inhibits
      Schwann cell proliferation but has no effect on axonal outgrowth.
AB  - In the present study the role of cAMP for axonal outgrowth and Schwann cell
      proliferation was studied using the cultured frog sciatic nerve. An intrinsic
      rise in nerve and ganglionic cAMP could be measured as a response to nerve
      injury, both in vitro and in vivo. Treatment with 0.1-1.0 microM forskolin, an
      activator of the cAMP-generating enzyme adenylyl cyclase, increased the cAMP
      content up to 13-fold, but was yet without effect on axonal outgrowth during an 8
      day culturing period. HA-1004, an inhibitor of cAMP-dependent protein kinase,
      also lacked effect on the regeneration. In contrast, the proliferation of Schwann
      cells, measured as [3H]thymidine incorporation, was inhibited to about 70% of
      control by forskolin, whereas HA-1004 stimulated proliferation to approximately
      130% of control. The results suggest that cAMP is involved in the injury-induced
      proliferation of Schwann cells of an adult peripheral nerve but that it lacks a
      central role in the regeneration of sensory axons of such nerves.

PMID- 8531227
TI  - Distribution of transforming growth factor-beta isoforms in the mammalian retina.
AB  - The distribution of transforming growth factor-beta (TGF-beta) was examined in
      the posterior segment of the monkey, human, and feline eye using antisera to TGF
      beta 1, TGF-beta 2, or TGF-beta 3. A number of different antibodies, tissue
      processing methods, immunolocalization techniques, and microscopic imaging
      systems were used in an attempt to gain a more comprehensive picture of TGF-beta
      isoform distribution in the retina and retinal pigmented epithelium (RPE). The
      results are generally consistent in identifying one or more of the three TGF-beta
      isoforms in the cytoplasm of a small, overlapping subset of cells. RPE cells,
      photoreceptors, Mueller cells, ganglion cells, hyalocytes, and cells associated
      with choroidal and retinal vessels are all represented in this immunoreactive
      population. No evidence of extracellular labeling was noted. The intracellular
      distribution of the three isoforms is distinctly different in photoreceptors.
      Anti-TGF-beta 1 precursor and anti-TGF-beta 2 immunoreactivity is confined
      primarily to rod outer segments, whereas anti-TGF-beta 3 immunoreactivities are
      restricted to mitochondria within inner segments. In the RPE, clusters of anti
      TGF-beta 2 positive cytoplasmic granules are located near the cells' lateral
      borders, whereas anti-TGF-beta 3 labeling is concentrated apically. These results
      provide baseline information from which new hypotheses regarding the function(s)
      of TGF-beta isoforms in the retina can be formulated.

PMID- 8531228
TI  - Association of nerve growth factor mRNA levels with MK-801-induced explosive
      behaviors in mice.
AB  - MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor,
      stimulated an outbred strain of NIH Swiss mice to display discrete episodes of
      explosive jumping behavior, designated as "popping." The rapid onset of the MK
      801-induced "popping" seems to follow the rapid distribution of the drug to the
      frontal cortex, the area that contains high levels of NMDA receptors. We examined
      the effect of this drug on the levels of mRNA coding for nerve growth factor
      (NGF) in the frontal cortex in relation to the exhibited "popping" episodes. Mice
      treated with 1 mg/kg MK-801 could be split into two groups based on the total
      number of "popping" episodes in a 30 min post-injection period. These groups also
      differed in the steady-state levels of frontal cortex NGF mRNA. Animals that
      exhibited low numbers of "popping" had levels of NGF mRNA significantly higher
      than saline treated controls or mice that exhibited high numbers of "popping."
      Mice treated with 10 mg/kg MK-801 had a high frequency of "popping" that was
      impossible to separate into episodes. In addition, these mice had levels of
      frontal cortex NGF mRNA that were significantly lower than either group of mice
      treated with 1 mg/kg MK-801. These data indicated that there was an increased
      level of NGF mRNA under conditions where MK-801 induced a low level of "popping"
      behavior. However, when "popping" intensified, NGF mRNA levels were decreased,
      suggesting a possible behavioral antagonism of the NGF response.

PMID- 8531229
TI  - Inhibition of the ATP-sensitive potassium channel in the guinea pig substantia
      nigra by BMS 181100 is not mediated by a sigma-binding site.
AB  - Quantitative autoradiography of brain tissue has revealed a high density of
      binding sites for the K-ATP channel antagonists, the sulphonylureas, and for
      sigma-ligands in the substantia nigra (SN). In view of the high density of the
      two binding sites in the SN the possibility has been investigated that the K-ATP
      channel and the sigma-binding site are functionally linked. The K-ATP channel
      mediated membrane hyperpolarisation and decrease in input resistance produced by
      hypoxia and by the metabolic inhibitor, cyanide, in rostral substantia nigra pars
      compacta neurons are antagonised by the sigma-ligand BMS 181100. In addition, BMS
      181100 antagonises activation of the K-ATP channel by diazoxide; cromakalim is
      found to be without effect in these neurons. Antagonism of the cyanide-induced
      hyperpolarisation is dose dependent and is observed at concentrations of the drug
      which have no observable effect on the resting membrane properties of the
      neurons. By contrast, the nonselective sigma ligands 1,3-di-O-tolylguanidine (10
      microM) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (100 microM), and the
      selective sigma 1-ligand (+)-pentazocine (5-10 microM) have no effect on the
      cyanide-induced hyperpolarisation. 5-HT (50-100 microM) and the selective 5-HT1A
      receptor agonist 8-OH-DPAT (50 microM) also fail to antagonise the cyanide
      induced hyperpolarisation. The antagonism of the cyanide-induced
      hyperpolarisation by BMS 181100 persists in the presence of tetrodotoxin (1
      microM) and in the presence of high concentrations of (+)-3-(3-hydroxyphenyl)-N
      (1-propyl)piperidine, but not under conditions of reduced calcium (0.1-0.2 mM)
      and raised magnesium (6 mM) concentrations, which block synaptic transmission. It
      is concluded that in substantia nigra phasic neurons the sigma-binding site does
      not regulate activation of the ATP-sensitive channel. However, BMS 181100
      antagonises K-ATP channel activation in these neurons independently of sigma
      binding sites and 5-HT receptors. This action of BMS 181100 is TTX insensitive
      and Ca2+ dependent.

PMID- 8531230
TI  - Several extracellular domains of the neural cell adhesion molecule L1 are
      involved in homophilic interactions.
AB  - The neural cell adhesion molecule L1 is a multidomain protein that plays
      important roles in cell adhesion, migration, and neurite outgrowth. It can
      interact with itself by a self-binding, i.e., homophilic adhesion mechanism
      (Kadmon et al.: J Cell Biol 110: 193-208, 1990a). To determine the domains of L1
      involved in homophilic binding, we have generated protein fragments of L1 in a
      prokaryotic and a eukaryotic expression system and used these covalently coupled
      to fluorescent microspheres to quantify aggregation between them by
      cytofluorometric analysis. Protein fragments containing the first and second Ig
      like domains and the third fibronectin type III homologous repeat showed avid
      self-binding. Ig-like domains III and IV also showed some self-binding, whereas
      Ig-like domains V and VI and fibronectin type III homologous repeats 1 and 2 as
      well as 4 and 5 were less or not active. Binding between different domains was
      also observed: fibronectin type III homologous repeats 4 and 5 interacted with Ig
      like domains I and II, and fibronectin type III homologous repeats 3-5 interacted
      with all Ig-like domains. These results were confirmed by experiments testing the
      binding of fragment-conjugated microspheres to substrate-coated L1 or to cell
      surface-expressed L1 on cultured neurons. Binding of L1 to itself was interfered
      with by all protein fragments tested, suggesting that also less avidly binding
      domains of L1 contribute to homophilic binding. These observations indicate
      prominent functional roles of both Ig-like domains and fibronectin type III
      homologous repeats in homophilic binding of L1.

PMID- 8531231
TI  - GABA-induced motility of spinal neuroblasts develops along a ventrodorsal
      gradient and can be mimicked by agonists of GABAA and GABAB receptors.
AB  - During embryogenesis, neuroblasts proliferate within germinal zones, then migrate
      to their final positions. Although many neurons migrate along radial glial
      fibers, evidence suggests that environmental factors, as yet unidentified, also
      influence neuroblast movement. In vivo, nerve growth factor (NGF) and gamma
      aminobutyric acid (GABA) colocalize near target destinations of migratory
      neuroblasts. In vitro, embryonic spinal neurons migrate towards NGF and GABA
      (Behar et al.: J Neurosci 14:29-38, 1994), implying that the molecules may act as
      chemoattractants in vivo. Here, we have used an in vitro assay of migration to
      show that migratory responses to these attractants develop along a ventrodorsal
      gradient that parallels terminal mitosis during cord development, and that GABA
      stimulates chemokinesis (motility without a gradient) via heterogeneous receptors
      involving separate signalling pathways. Both GABAA (muscimol) and GABAB
      (baclofen) agonists mimicked the effects of GABA in stimulating chemokinesis.
      Muscimol-induced motility was only blocked by GABAA antagonists (bicuculline or
      picrotoxin), whereas migration to baclofen was blocked by antagonists of both
      GABAA and GABAB (2-hydroxysaclofen) receptors. Migration to baclofen, but not
      muscimol, was abolished in the presence of 8-bromo cAMP or pertussis toxin,
      indicating that the former, but not the latter, attractant may stimulate motility
      via Gi/Go GTP binding proteins, and that PKA may modulate migratory responses to
      baclofen. Migration to GABA was partially attenuated by each of the GABA receptor
      antagonists. These results lead us to conclude that the natural ligand stimulates
      neuroblast motility via heterogeneous receptors coupled to different signalling
      mechanisms.

PMID- 8531232
TI  - Effects of diphenyl dimethyl dicarboxylate on oral tolerance to ovalbumin in
      mice.
AB  - The effects of diphenyl dimethyl dicarboxylate (PMC) on oral tolerance to
      ovalbumin (OVA) were investigated in C3H/HeN and BALB/c mice. Mice orally
      received 20 mg OVA or 20% starch solution were immunized 7 days later with an
      i.p. injection of 0.1 mg OVA in complete Freund's adjuvant (CFA). The effects of
      oral OVA and PMC on antibody production were assessed by ELISA of immunoglobulin
      (Ig) subclass level in serum collected 7 days after immunization. Oral tolerance
      was obtained enough on day 7 after immunization and was more effective in C3H
      strain than in BALB strain, associated with decreases of anti-OVA IgG, IgG1,
      IgG2a and IgM levels. After oral OVA, oral administration of PMC for 6 days
      significantly elevated anti-OVA IgG, IgG1, IgG2a and IgM levels in mice
      hyposensitized by the oral OVA. These findings indicate that PMC is an useful
      modulator of oral tolerance to OVA in these two strains.

PMID- 8531233
TI  - Effects of all-trans-retinoic acid on limb development in the genetic polydactyly
      mouse.
AB  - Pdn/+ female mice, mated with Pdn/+ males, were treated with 40 mg/kg body weight
      of all-trans-retinoic acid (RA) intraperitoneally on day 10 or 11 of gestation,
      and effects on the limb development were investigated. RA treatment induced the
      shortening of stylopodium and zygopodium. In the present experiment, we focused
      on the differences between genotypes in the shortening of stylopodium and
      zygopodium induced by RA. The effects of RA were milder in Pdn/Pdn than +/-
      (Pdn/+ and/or +/+) fetuses. The differences between genotypes in the effects of
      RA were more significant in the group treated on day 11 than on day 10 of
      gestation. Cartilage of stylopodium and zygopodium was longer in day-13 Pdn/Pdn
      embryos exposed to RA on day 11 of gestation than those in similarly treated +/-
      embryos. Many apoptotic cells were observed in the mesenchyme of the forelimb
      plates at 12 hr after injection of RA on day 11 of gestation. These results
      suggest that the Pdn gene might influence the apoptosis induced by RA in the
      mesenchymal cells of the limb, causing milder effects in the shortening of
      stylopodium and zygopodium in Pdn/Pdn fetuses.

PMID- 8531234
TI  - Effect of repeated administrations of neomycin on the neuromuscular functions and
      the enhancement of d-tubocurarine action in mice.
AB  - Effects of repeated s.c. treatments with 50 mumol (approx. 31 mg)/kg/day of
      neomycin for 10 or 15 days were examined in mice. There were no significant
      differences between saline and neomycin treatment groups in the motor
      coordination assessed by rota-rod test and traction test. On tension recordings,
      an in vitro addition of d-tubocurarine inhibited the twitch tensions evoked by
      the nerve stimulations in both cases of saline or neomycin treatment. Neomycin
      treatments shifted the concentration-response curve between twitch tension and d
      tubocurarine to the left, dependently on its injection days. These results
      suggest that repeated treatments with neomycin enhance the inhibitory effect of d
      tubocurarine on the neuromuscular transmission in mice without eliciting motor
      incoordination and muscle relaxation.

PMID- 8531235
TI  - Effects of pentoxifylline on active oxygen-induced sister-chromatid exchange.
AB  - Active oxygens cause major tissue damages in a number of distress syndromes.
      Pentoxifyline (POF) and its metabolites, a methylxanthine derivative, are
      inhibitors of superoxide anion production in stimulated human leukocytes.
      Examination was made of the effects of POF on the genotoxic actions of active
      oxygens. The frequency of sister-chromatid exchanges (SCEs) induced by paraquat
      (PQ), a generator of superoxide anions was significantly reduced in cultured
      Chinese hamster lung cells (CHL/IU) pretreated with POF. POF metabolite samples
      were also effective. Superoxide anion scavenging effect of POF were found at 0.1
      mM, and it was more potent than that of POF metabolite samples. POF and its
      metabolite sample inhibited xanthine oxidase (XOD) at 1 mM but not at 0.1 mM. POF
      would thus appear to protect cells from the toxic effects of active oxygens on
      chromosomes and tissue damage by not only inhibition of active oxygen production
      in leukocytes but also by scavenging activity of active oxygens.

PMID- 8531236
TI  - Morphological evaluation of cyclophosphamide testicular toxicity in rats using
      quantitative morphometry of spermatogenic cycle stages.
AB  - The testicular toxicity of cyclophosphamide (Cp) in rats was evaluated by
      quantitative morphometry of spermatogenic cycle stages. Nine-week-old male
      Sprague-Dawley rats in Group 1 were given a single oral administration of 100
      mg/kg of Cp, and were sacrificed at 1, 7, 14 and 21 days thereafter. Rats in
      Group 2 were orally given 100 mg/kg/day of Cp for 2 days, followed by 50
      mg/kg/day for the next 3 days, and were sacrificed at 1 and 4 days after the last
      administration. The numbers of seminiferous epithelia were counted in the
      seminiferous tubules of stages II, V, VII and XII of the spermatogenic cycle. The
      data were expressed as numbers of spermatogenic cells per Sertoli cells per
      seminiferous tubule cross section. Animals in Group 1 showed decreased
      preleptotene spermatocytes at Day 7, decreased zygotene spermatocytes at Day 14,
      and decreased pachytene spermatocytes at Day 21. In group 2, testicular toxicity
      could also be clearly detected by this morphometric approach. The present
      morphometric study thus indicates that testicular toxicity can be detected from
      Day 7 even after a single administration of Cp.

PMID- 8531237
TI  - Effects of nifedipine on physical dependence on barbital or diazepam in rats.
AB  - The effects of nifedipine on the development of physical dependence on barbital
      and diazepam in rats were examined using the drug-admixed food method. Rats were
      chronically treated with either barbital- or barbital in combination with
      nifedipine-admixed food for 28 days, and with either diazepam- or diazepam in
      combination with nifedipine-admixed food for 26 days, on schedules of gradually
      increasing doses of barbital or diazepam. Withdrawal was conducted by
      substituting normal food for drug-admixed food on the last day of the treatment.
      Co-administration of nifedipine with barbital potentiated weight loss and
      withdrawal scores after the termination of barbital treatment. However, the
      withdrawal signs after the termination of diazepam treatment were not affected by
      co-administration of nifedipine with diazepam. These results suggest that
      nifedipine potentiates the development of physical dependence on barbital but not
      diazepam. It is known that co-administration of dihydropyridine derivative
      nitrendipine suppresses the development of physical dependence on ethanol. Basing
      on the differences in sensitivity of central depressants, barbiturates,
      benzodiazepines and ethanol, to three types of voltage-dependent Ca2+ channels,
      such as L-, N- and T-types studied so far, the development of physical dependence
      on central depressants may be modified differently by L-type Ca2+ channel
      blockers, corresponding to respective depressants.

PMID- 8531238
TI  - Development of alternative methods.
AB  - This presentation will raise specific issues and explore areas that need
      discussion and development of mechanistically based tests in toxicology. In
      addition, an approach to validation will be presented that is based on
      fundamental principles and modeled after actual practice in other areas of
      methodology acceptance. Further, it is recognized that the validation process is
      but only one aspect of incorporation of in vitro approaches into safety
      evaluation and risk assessment.

PMID- 8531239
TI  - Stress proteins are sensitive indicators of injury in the brain produced by
      ischemia and toxins.

PMID- 8531240
TI  - Design and evaluation of rodent carcinogenicity studies (bioassay).

PMID- 8531241
TI  - Analysis of carcinogenic risk based on mode of drug action.

PMID- 8531242
TI  - Dose selection for carcinogenicity studies of pharmaceuticals.

PMID- 8531243
TI  - Usefulness of in vivo short-term studies on carcinogenic risk assessment.

PMID- 8531244
TI  - The use of biotechnical recombinant-mice to test the safety of potential
      carcinogenic pharmaceuticals.

PMID- 8531245
TI  - Interaction between endocrine and immune system.

PMID- 8531246
TI  - FK506: mechanism of immunosuppression and adverse-effects.

PMID- 8531247
TI  - The mechanisms of action of cyclosporin A : implications for its side effects.

PMID- 8531248
TI  - Muromonab CD3 (Orthoclone OKT3).

PMID- 8531249
TI  - Cytotoxic therapy and side effect in childhood.

PMID- 8531250
TI  - Human dental plaque formation on plastic films. A quantitative SEM study.
AB  - The initial colonization of bacteria in previously clean teeth or artificial
      surfaces inserted in mouth has been reported to occur at various periods of time.
      Ronstrom et al., using light microscopy, saw that bacteria were present 10
      seconds after prophylaxis. Bacterial culture studies have shown that
      microorganisms associated with the surface coating on tooth surfaces appeared
      within minutes after prophylaxis. Furthermore, Ronstrom et al. noted that the
      number of bacteria increased over a period of four hours. In contrast,
      ultrastructural investigations of early plaque have demonstrated bacterial
      colonization only within the first two hours of plaque development in a few
      samples obtained on a smooth surface and in most samples on a rough surface.
      However, microorganisms have been found regularly after four hours of plaque
      accumulation in subjects with healthy gingiva. The aim of the present
      investigation was to determine the earliest occurrence of bacterial colonization
      in situ and to observe the pattern of the initial formation of human dental
      plaque.

PMID- 8531251
TI  - Lack of evidence for hypophosphatasia as a factor in the pathogenesis of early
      onset periodontitis.
AB  - Hypophosphatasia, an inheritable metabolic disorder affecting calcification, has
      been shown to have various oral manifestations. Recently, it was suggested that
      it may serve as a predisposing factor in the pathogenesis of early-onset
      periodontitis. The present study was designed to examine the frequency of
      hypophosphatasia among patients with juvenile periodontitis and rapidly
      progressive periodontitis. Eighteen patients, nine females and nine males (age 19
      37 years, mean 23.2 years), were included in this study. Venous blood and urinary
      samples were collected and assayed for alkaline phosphatase and urinary
      phosphoethanolamine. Mean alkaline phosphatase levels (109 +/- 35 IU/L) were
      within the normal limits for all patients except one who exhibited slightly lower
      than normal values. Urinary phosphoethanolamine, a typical marker of
      hypophosphatasia, was absent from all specimens, which rules out the possible
      diagnosis of such disorder in these patients. Until more information is
      available, the role of hypophosphatasia as a predisposing factor in early-onset
      periodontitis is yet to be established.

PMID- 8531252
TI  - Root coverage techniques: a review.
AB  - Gingival recession with the exposure of root surfaces is a significant treatment
      problem facing the clinician. Controversy relative to treatment continues and
      centers primarily around the need for gingival width augmentation. In 1972, Lang
      and Loe advanced the concept that a true minimal width of keratinized gingival
      tissue was necessary for health. They showed that all surfaces with less than 2
      mm of keratinized gingiva exhibited clinical inflammation and varying amounts of
      gingival exudate. In contrast, 80% of the surfaces with more than 2 mm of
      keratinized gingiva were clinically healthy, and 76% of these same surfaces
      failed to show gingival exudate. Since 1972, the majority of studies have found
      that minimizing inflammation is sufficient to maintain attachment levels, even in
      the absence of "adequate" widths of keratinized and attached gingiva. Certain
      situations may enhance recession, such as subgingival restorations and
      toothbrushing trauma, but if inflammation is controlled and the etiology
      eliminated, minimal amounts of keratinized gingiva can be maintained in a state
      of health without further recession. Such findings have led to the current
      concept that deemphasizes a need for gingival augmentation surgery when there is
      no accompanying need for root coverage. A requirement for root surface coverage
      arises when gingival recession has esthetic implications, where exposure has
      resulted in root sensitivity, or where recession complicates routine home care
      procedures. While agreement exists relative to the indications for root coverage,
      there are a variety of surgical techniques that can accomplish this end. The
      purpose of this paper is to review these techniques and to examine the
      indications for choosing one procedure over another.

PMID- 8531253
TI  - Mechanisms of stimulus transmission across dentin--a review.
AB  - Several investigators have demonstrated that intradental A-type (A beta and A
      delta) nerve fibers are responsible for the sensitivity of dentin and that the
      endings of the responding fibers are located in the pulp-dentin area of the
      tooth. The exact mode of transmission of stimuli (e.g., thermal, chemical,
      mechanical, etc.) across dentin, however, is still unclear, although several
      hypotheses have been proposed. These include direct nerve stimulation, dentinal
      receptor (transducer/modulation), hydrodynamic, and direct ionic diffusion
      hypotheses. Currently, the most accepted mechanism of intradental nerve
      activation associated with dentin sensitivity appears to be hydrodynamic in
      nature, although alternative mechanisms of transmission (e.g., direct ionic
      diffusion) cannot be ruled out. Recent investigations (in the cat), however,
      appear to provide evidence substantiating the hydrodynamic hypothesis.

PMID- 8531254
TI  - Hypothyroidism in the newborn.

PMID- 8531255
TI  - Genital infections in the aetiology of late fetal death: an incident case
      referent study.
AB  - Women with prelabour fetal death in the third trimester were recruited in order
      to study the association between intra-uterine death and maternal genital
      colonization of bacteria. Fifty-eight women with verified fetal death were
      compared with a group of 58 women matched for age, parity and gestational length
      (the first referent group) and with women delivering liveborn neonates (second
      referent group). Cultures from the vagina, the endocervix, the amniotic fluid,
      the placenta, the conjunctivae of the newborn and the secretion of gastric
      aspirate of the newborn were carried out. Blood was taken for haemoglobin, thick
      film (malaria) and syphilis and HIV serology. Cases were more affected by
      previous stillbirths than first referents (OR = 11.88). Preterm delivery was
      significantly more common in cases than in second referents (OR = 57.70). Cases
      had significantly more often < 3 ANC visits (OR = 2.81). Cases had a lower body
      mass index than first referents (OR = 2.38). Temperature > or = 37 degrees C was
      12 times more frequent in cases than in first referents (OR = 21.20) and four
      times more frequent than in second referents (OR = 6.60). Average birth weight
      among stillborns was 1954 g and in liveborns 3223 g (P = 0.001). The
      corresponding prevalence of LBW was 78% in cases and 0% among second referents (P
      < 0.001). Histological chorioamnionitis was significantly prevalent in cases than
      in second referents (OR = 4.97). Syphilis was significantly more common in cases
      than in first (OR = 7.71) and in second referents (OR = 5.30).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8531256
TI  - An incident case-referent study of threatening preterm birth and genital
      infection.
AB  - A total of 53 pregnant Mozambican women identified as having painful uterine
      contractions in the preterm period were studied and compared to referents,
      matched for age, parity, and gestational length, without such contractions. Both
      groups were studied regarding socio-economic and obstetric background factors,
      current clinical features, and microbiological findings in the lower genital
      tract. Cases tended to seek antenatal care earlier than referents. Salaried work
      outside the home was more common among cases (OR = 16.9). It was shown that
      affected cases had significantly more antenatal card risk factors (OR = 3.4) and
      that 10 times more cases than referents had elevated body temperature (OR =
      16.7). Anaemia was more common among cases than among referents (OR = 3.7) and
      malaria parasitaemia was over-represented among cases (OR = 12.4). Mid-upper-arm
      circumference was shorter among cases than among referents (OR = 2.4). Anaerobic
      bacteria tended to be isolated from endocervix more often among cases than among
      referents (OR = 2.4). Only one woman in the study was HIV-1-positive. It is
      concluded that febrile infection is strongly associated with preterm labour and
      that salaried work outside home, anaemia, and malaria are significant risk
      factors in the setting studied.

PMID- 8531257
TI  - Prevalence and age-specific incidence of burns in Ghanaian children.
AB  - The incidence of burns in developing countries is not precisely known due to
      unavailability or incompleteness of death registration and disease reporting. In
      this study, we determined prevalence and age-specific incidence of burns in
      children 0-5 years in the Ashanti region of Ghana using burn scars as proxy. We
      used a community-based, multi-site survey to identify children who had scars as
      evidence of previous burns. A scar prevalence of 6 per cent was found. No sex
      differences were found. However, significant differences were found among age
      groups, with children aged 18-23 months having the highest incidence (57.4 per
      1000 person-years). There was evidence of focal occurrence of childhood burns in
      certain districts, and a higher prevalence in rural areas. We conclude that
      childhood burns are a significant health problem in Ghana, especially among rural
      residents and the very young, and recommend that interventions be developed to
      control them.

PMID- 8531258
TI  - Predictors of diarrhoea in young Bangladeshi children.
AB  - This study investigated diarrhoea episodes in 196 children aged 6-23 months in
      relation to their diarrhoea experience in the first 6 months of life, domestic
      hygiene, and number of other children aged < 5 years in the household. Diarrhoea
      episodes were recorded weekly, while observations on domestic hygiene behaviour
      patterns were made once in 1982 and 1983. Correlation and regression analyses
      suggest that diarrhoea experience in the first 6 months of life was positively
      associated with diarrhoea episodes in ages 6-23 months. The strength of
      association improved a little, but significantly by controlling for mothers'
      handwashing, but did not improve by controlling for disposal of faeces and use of
      tube-well water for domestic use. The number of other children aged < 5 years in
      the household was an independent predictor of diarrhoea episodes in the age group
      6-23 months.

PMID- 8531259
TI  - Epidemic Shigella dysenteriae type 1 in Natal.
AB  - Since its first isolation in South Africa in 1994, Shigella dysenteriae type 1
      has now spread to cause an epidemic outbreak in Natal Kwazulu, resulting in a
      steep rise in admissions for dysentery and the haemolytic uraemic syndrome in
      children. We report on the epidemic as it has evolved so far. A large outbreak is
      to be expected in South Africa in view of large scale poverty, lack of housing,
      and adequate water and sanitation, unless urgent public health measures are
      taken.

PMID- 8531261
TI  - Assessment of vitamin A nutriture in preschool children--a multi-approach.
AB  - Previous studies suggest that impression cytology may be a reliable test to
      detect mild xerophthalmia in young children. The present study was conducted to
      assess Vitamin A nutriture in 150 preschool children through a multi-approach,
      wherein the correlation of impression cytology, with other indicators of Vitamin
      A status was examined. A close correlation between keratinization of buccal
      mucosal cells and vitamin A deficiency even in subclinical states has been noted.

PMID- 8531260
TI  - Circulating growth hormone (GH), insulin-like growth factor-I (IGF-I) and free
      thyroxine, GH response to clonidine provocation and CT scanning of the
      hypothalamic-pituitary area in children with sickle cell disease.
AB  - Serum growth hormone (GH), cortisol, free thyroxine (FT4), thyroid-stimulating
      hormone (TSH), and insulin like growth factor I (IGF-I) concentrations were
      measured in 15 children with sickle cell disease (SCD) together with their
      heights < 5th percentile for age and gender, and in 15 healthy age-matched
      children who had normal variant short stature (NVSS). GH response to an oral dose
      of clonidine (0.15 mg/m2) and cortisol response to ACTH stimulation were
      determined in the two groups. Children with SCD had significantly lower serum
      concentrations of IGF-I and decreased GH response to stimulation. Eight out of
      the 15 children with SCD did not mount an appropriate GH response to clonidine
      provocation (> 10 micrograms/l). CT scanning of the hypothalamic-pituitary area
      in those eight children with SCD revealed a partial or complete empty sella in
      all of them. It appears that defective GH release, and consequently low IGF-I
      production and slow growth velocity in children with SCD might be secondary to
      hypoxic-vascular insults to their hypothalamic-pituitary axis during one or more
      of the sickling episodes.

PMID- 8531262
TI  - Serum cortisol levels in children with dengue haemorrhagic fever.
AB  - Dengue Haemorrhagic Fever (DHF) is a serious and often fatal paediatric problem
      in Myanmar. Acute and convalescent serum cortisol levels were measured in 62
      children with dengue infection to study cortisol sufficiency in this disease.
      Twenty-six children with non-dengue acute viral infection were also included as
      controls. In acute stage, highest mean serum cortisol level (655.4 +/- 72.18
      nmol/l) was observed in DHF cases presenting with shock, followed by DHF non
      shock cases (640.56 +/- 74.58 nmol/l) and dengue fever cases (617.2 +/- 75.38
      nmol/l). Cases with DHF had significantly higher serum cortisol level (P < 0.05)
      than in controls (444.41 +/- 59.71 nmol/l). In cases of DHF, mean serum cortisol
      level during the acute stage was found to be significantly two-fold higher than
      the convalescent stage. We found no cortisol insufficiency in cases of dengue
      haemorrhagic fever during acute and convalescent stages of illness.

PMID- 8531263
TI  - Kala-azar: experience from a non-endemic area in India.
AB  - Resurgence of Kala-Azar in India has posed many problems. Apart from patients
      from endemic areas, cases are being reported from non-endemic areas also. In the
      present series, four out of 26 patients were from non-endemic areas. Other than
      diagnostic difficulties, resistance to stibogluconate and relapse are common
      problems which were seen in eight patients. The clinical profile of cases, their
      management, and how the problem of resistance was tackled are described.

PMID- 8531264
TI  - Viral diarrhoea in a rural coastal region of Karnataka India.
AB  - A total of 106 children below 5 years of age admitted to the Kasturba Medical
      College Hospital Manipal Karnataka (South India) were investigated over a period
      of 6 months to determine the aetiological role of viruses in acute diarrhoea.
      Viral aetiological agents isolated were Rotaviruses in 12 (11 per cent) cases,
      Adenoviruses in 3 (3 per cent) cases, coronavirus and astroviruses in two (2 per
      cent) cases each. Non-viral isolates were Cryptosporidium and Salmonella
      typhimurium in two cases each, and Entamoeba histolytica and Shigella flexneri in
      one case each.

PMID- 8531265
TI  - Shigellosis in children from north India: a clinicopathological study.
AB  - Stool samples of 1488 children suffering from acute diarrhoea were studied for
      bacterial culture and sensitivity. Shigella culture was positive in 143 (10 per
      cent) children and 53 hospitalized children could be studied in detail. Thirty
      six (68 per cent) children were under 2 years of age and peak prevalence was
      observed in summer months. Fever and diarrhoea were universal features; 96 per
      cent had blood and mucus in the stools, but 32 per cent started with watery
      diarrhoea lasting 1-3 days followed by dysentery. Two cases (4 per cent) had
      watery diarrhoea. Abdominal pain dehydration, and malnutrition were present in
      more than two-thirds of the cases. Central nervous systemic (CNS) manifestations,
      renal failure, respiratory manifestations, and subacute intestinal obstruction
      were seen in 45, 25, 17, and 5 per cent of cases, respectively. Shigella
      dysenteriae was the commonest organism grown in 57 per cent, followed by Shigella
      flexneri in 36 per cent, Shigella boydii in 4 per cent, and Shigella sonnei in 4
      per cent cases. In the majority, the organisms were sensitive to neomycin (83 per
      cent), furazolidine (86 per cent), and cephaloridine (87 per cent), whereas
      Shigella strains were resistant to tetracycline in 93 per cent, ampicillin in 83
      per cent, chloramphenicol in 91 per cent and cotrimoxazole in 66 per cent cases.
      Proctosigmoidoscopy was useful in defining the nature of mucosal lesion, to
      collect swabs for culture and biopsy specimen for histopathology. Four (8 per
      cent) cases had pseudomembrane and in two cases Clostridium difficile could be
      identified. Eight (15 per cent) cases died and two of them had
      shigellaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531266
TI  - Bacterial meningitis: still a cause of high mortality and severe neurological
      morbidity in childhood.
AB  - Among 121 cases of bacterial meningitis (age 2 months to 12 years; mean, 35
      months) treated over a 3-year period, Neisseria meningitidis was the most common
      pathogen (33 per cent), then Haemophilus influenzae (32 per cent) and
      Streptococcus pneumoniae (15 per cent). In the H. influenzae group, 95 per cent
      were aged below 2 years. Overall mortality was 12 per cent: higher in the S.
      pneumoniae (17 per cent) and less common organism (21 per cent) groups.
      Neurological sequelae in 21 (20 per cent) of the 106 survivors included hearing
      impairment in 17 and quadriparesis in eight. Meningitis caused by S. pneumoniae
      contained a significantly higher proportion of children with neurological
      morbidity (P = 0.0128). The addition of dexamethasone treatment during the third
      year produced an apparent but not significant trend towards less mortality (P =
      0.7568), fewer neurological sequelae (P = 0.3401) and less hearing impairment (P
      = 0.3903). Despite the availability of effective chemotherapy, bacterial
      meningitis will remain an important cause of high mortality and considerable
      morbidity.

PMID- 8531267
TI  - The value of neonatal autopsies.
AB  - Autopsy was performed on 221 of the 223 neonatal deaths that occurred over a
      period of 3 years (1989-1991). Clinically active problems at the time of death
      were identified in a combined clinicopathological approach. Prematurity
      associated conditions accounted for 51 per cent of deaths. Autopsy alone gave the
      diagnosis in 22 per cent of cases, confirmed the clinically suspected diagnosis
      in 68 per cent of cases and in 9 per cent of cases it was non-contributory; 69
      per cent of deaths were considered non-preventable in our centre.

PMID- 8531268
TI  - Second revision of mortality prevention potential of conservative neonatal care.

PMID- 8531269
TI  - Field test of the vitamin A dispenser.

PMID- 8531270
TI  - Methodological aspects of a household survey on diarrhoeal diseases in a peri
      urban community of South Africa--the problem of defining diarrhoea.

PMID- 8531271
TI  - National public health leader Caswell Evans talks of 'doing less with less'.
      Interview by Thomas Cole.

PMID- 8531272
TI  - Health pros want new rules for girl athletes.

PMID- 8531273
TI  - Military medicine has NATO role in Balkans.

PMID- 8531274
TI  - From the Centers for Disease Control and Prevention. Prevention and managed care:
      organizations, purchasers of health care, and public health agencies.

PMID- 8531275
TI  - From the Centers for Disease Control and Prevention. Update: respiratory
      syncytial virus activity--United States, 1995-96 season.

PMID- 8531276
TI  - Survival and conservative treatment for localized prostate cancer.

PMID- 8531277
TI  - Survival and conservative treatment for localized prostate cancer.

PMID- 8531278
TI  - Clinical crossroads: alcoholism and HIV infection.

PMID- 8531279
TI  - Systems analysis of adverse drug events.

PMID- 8531280
TI  - Systems analysis of adverse drug events.

PMID- 8531281
TI  - Identifying ways to reduce surgical errors.

PMID- 8531282
TI  - Depression and survival among HIV-infected persons.

PMID- 8531283
TI  - HIV-1 shedding and chlamydial urethritis.

PMID- 8531284
TI  - Efficacy of acellular pertussis vaccine in early childhood after household
      exposure.
AB  - OBJECTIVE: To evaluate the efficacy of a three-dose primary vaccination with a
      diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical"
      pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of
      Bordetella pertussis infection by culture or serology. DESIGN: Passive monitoring
      for suspected first household (index) cases of typical pertussis in six areas in
      Germany comprising 22,505 children vaccinated with study vaccine at 3, 4, and 5
      months of age. Blinded, prospective follow-up of household contacts of index
      cases for incidence and progression of pertussis. SETTING: Six areas in Germany
      with a high incidence of pertussis. SUBJECTS: Four hundred fifty-three households
      with index cases comprising 360 evaluable contacts eligible for analysis of
      vaccine efficacy. MAIN OUTCOME MEASURE: Vaccine efficacy from attack rates of
      pertussis in household contacts classified by vaccination status. RESULTS: Of the
      173 nonvaccinated household contacts, 96 developed typical pertussis, compared
      with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine
      efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6%
      to 94.6%). Protection did not wane until at least the time recommended for
      booster vaccination. None of the analyzed potential confounding factors--age,
      socioeconomic status, erythromycin treatment, household composition, center
      effect, and selection bias--influenced study results in favor of the vaccine.
      CONCLUSIONS: Under conditions of intense household exposure, primary vaccination
      with acellular vaccine protected against pertussis until at least the time
      recommended for booster vaccination. The vaccine can be expected to be equally or
      more effective in settings with lower infectious pressure.

PMID- 8531285
TI  - Characteristics of firearms involved in fatalities.
AB  - OBJECTIVES: To document the types of firearms associated with firearm fatalities,
      and to determine the availability of information on firearm characteristics in
      existing data sources. DESIGN: Review of police, medical examiner, and crime
      laboratory records for all firearm homicides and review of medical examiner
      records for all suicides and unintentional and undetermined firearm fatalities.
      SETTING: City of Milwaukee, Wis, from 1990 through 1994. POPULATION: A total of
      175 firearm suicides and 524 firearm homicides. MAIN OUTCOME MEASURES: Source of
      data; circumstances and means of death; host demographic characteristics; firearm
      make, model, caliber, barrel length, and serial number. RESULTS: Handguns
      accounted for 468 (89%) of 524 firearm homicides and 124 (71%) of 175 firearm
      suicides. Handguns of .25 caliber accounted for 14% (n = 63) of 438 firearm
      homicides and 12% (n = 15) of all firearm suicides in which caliber was known.
      The Raven MP-25 was the single most commonly identified firearm and accounted for
      10% (n = 15) of 153 handgun homicide cases and 7% (n = 7) of the 76 suicide cases
      in which the manufacturer of the firearm was identified. From all data sources
      combined, information on firearm type was available in 681 (97%) of 699 cases,
      caliber/gauge in 636 cases (91%), manufacturer/model in 309 cases (44%), and
      serial number in 276 cases (40%). CONCLUSIONS: Inexpensive, short-barreled .25
      caliber handguns were the most common weapon type associated with firearm
      homicides and suicides in Milwaukee during 1990 through 1994. Product-specific
      information is a crucial part of planning appropriate injury countermeasures for
      firearms. In combination, police, crime laboratory, and medical examiner data can
      supply this information with modest changes in data collection procedures.

PMID- 8531286
TI  - Long-term postmenopausal hormone use, obesity, and fat distribution in older
      women.
AB  - OBJECTIVE: To determine whether long-term postmenopausal hormone replacement is
      associated with measures of obesity and body composition in elderly women.
      DESIGN: A 15-year prospective and cross-sectional cohort study. SETTING: Rancho
      Bernardo, a geographically defined community in Southern California.
      PARTICIPANTS: A total of 671 women aged 65 to 94 years, who were initially
      enrolled in the Rancho Bernardo Study between 1972 and 1974 and participated in a
      1988 to 1991 follow-up clinic visit. These women had never used hormone
      replacement therapy (n = 194), used hormones intermittently (n = 331), or used
      hormones continuously (n = 146) for the 15 years between baseline and follow-up.
      MAIN OUTCOME MEASURES: Height and weight were obtained at both clinic visits;
      differences in body mass index (BMI) between baseline and follow-up were
      computed. At follow-up, waist and hip circumferences and bioelectric impedance
      were measured. RESULTS: Age-adjusted comparisons indicated intermittent and
      continuous hormone users had significantly lower mean BMIs at baseline than women
      who had never used hormone replacement therapy. After adjustment for potentially
      confounding covariates, there were no significant differences between estrogen
      users and nonusers in BMI at follow-up, change in weight or BMI between baseline
      and follow-up, or waist-hip ratio or fat mass at follow-up. CONCLUSION: Hormone
      replacement therapy, whether used intermittently or continuously for 15 or more
      years, is not associated with the weight gain and central obesity that is
      commonly observed in postmenopausal women.

PMID- 8531287
TI  - The role of chronic alcohol abuse in the development of acute respiratory
      distress syndrome in adults.
AB  - OBJECTIVE: To determine the effect of a history of chronic alcohol abuse on the
      incidence of acute respiratory distress syndrome (ARDS) and in-hospital
      mortality. DESIGN: Prospective cohort study. PATIENTS: A total of 351 medical and
      surgical intensive care unit patients with one of seven at-risk diagnoses for the
      development of ARDS. MAIN OUTCOME MEASURES: The development of ARDS and in
      hospital mortality. RESULTS: Of the 351 patients enrolled in the study, the
      incidence of ARDS in patients with a history of alcohol abuse was significantly
      higher than in patients without a history of alcohol abuse (43% vs 22%) (P <
      .001; relative risk [RR], 1.98; 95% confidence interval [Cl], 1.32 to 2.85). In
      patients with sepsis, ARDS developed in 52% of the patients with a prior history
      of alcohol abuse compared with only 20% in patients without a history of alcohol
      abuse (P < .001; RR, 2.59; 95% Cl, 1.29 to 5.12). Fifty-one percent (52/102) of
      the patients who developed ARDS died compared with only 14% (36/249) of patients
      who did not develop ARDS (P < .001). In the subset of patients who developed
      ARDS, the in-hospital mortality rate was 65% in patients with a prior history of
      alcohol abuse. This mortality rate was significantly higher (P = .003) than the
      mortality rate in patients without a history of alcohol abuse (36%). CONCLUSIONS:
      A prior history of chronic alcohol abuse significantly increases the risk of
      developing ARDS in critically ill patients with an identified at-risk diagnosis.
      Our results may be useful in the earlier and more accurate identification of
      patients at high risk for developing ARDS.

PMID- 8531288
TI  - Carcinogenicity of lipid-lowering drugs.
AB  - OBJECTIVE: To review the findings and implications of studies of rodent
      carcinogenicity of lipid-lowering drugs. DATA SOURCES: Summaries of
      carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference
      (PDR), additional information obtained from the US Food and Drug Administration,
      and published articles identified by computer searching, bibliographies, and
      consultation with experts. STUDY SAMPLE: We tabulated rodent carcinogenicity data
      from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we
      selected a stratified random sample of antihypertensive drugs. We also reviewed
      methods and interpretation of carcinogenicity studies in rodents and results of
      clinical trials in humans. DATA SYNTHESIS: All members of the two most popular
      classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in
      rodents, in some cases at levels of animal exposure close to those prescribed to
      humans. In contrast, few of the antihypertensive drugs have been found to be
      carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from
      clinical trials in humans is inconclusive because of inconsistent results and
      insufficient duration of follow-up. CONCLUSIONS: Extrapolation of this evidence
      of carcinogenesis from rodents to humans is an uncertain process. Longer-term
      clinical trials and careful postmarketing surveillance during the next several
      decades are needed to determine whether cholesterol-lowering drugs cause cancer
      in humans. In the meantime, the results of experiments in animals and humans
      suggest that lipid-lowering drug treatment, especially with the fibrates and
      statins, should be avoided except in patients at high short-term risk of coronary
      heart disease.

PMID- 8531289
TI  - A 47-year-old woman with ductal carcinoma in situ.

PMID- 8531290
TI  - Does lowering cholesterol cause cancer?

PMID- 8531292
TI  - Perspectives on international medical practice.

PMID- 8531291
TI  - The firearm injury reporting system revisited.

PMID- 8531293
TI  - The Kobe earthquake: a chance to serve.

PMID- 8531294
TI  - Medical education, physician workforce, and health care delivery in Bulgaria.

PMID- 8531295
TI  - Seeking reconnection: impressions of an American medical student in Peru.

PMID- 8531296
TI  - Patient-physician communication: respect for culture, religion, and autonomy.

PMID- 8531298
TI  - Patient-physician communication: respect for culture, religion and autonomy.

PMID- 8531297
TI  - Patient-physician communication: respect for culture, religion, and autonomy.

PMID- 8531299
TI  - Patient-physician communication: respect for culture, religion, and autonomy.

PMID- 8531300
TI  - Patient-physician communication: respect for culture, religion, and autonomy.

PMID- 8531301
TI  - Cholesterol and coronary heart disease mortality in elderly patients.

PMID- 8531302
TI  - Cost-effectiveness of mammography screening.

PMID- 8531303
TI  - Cost-effectiveness of mammography screening.

PMID- 8531304
TI  - Cost-effectiveness of mammography screening.

PMID- 8531305
TI  - Adolescents with negative pregnancy test results. An accessible at-risk group.
AB  - OBJECTIVE: To estimate nationally what percentage of young women receive negative
      pregnancy test results before becoming pregnant, to explore their fertility and
      test histories, and to estimate the potential for intervention at the time of a
      negative test result. DESIGN: A cross-sectional study in which young women
      presenting to clinics for pregnancy tests were asked to complete a self
      administered questionnaire before test results were known that explored prior
      pregnancy tests, pregnancies, sexual and contraceptive histories, and
      childbearing attitudes. SETTING: Fifty-two clinics including hospital, health
      department, Planned Parenthood, and independent facilities. PARTICIPANTS: A total
      of 2926 patients aged 17 years or younger requesting pregnancy tests at
      presentation. RESULTS: Among young women who had ever conceived, 34.2% had a
      prior negative pregnancy test result and 24.4% had a prior negative test result
      at a clinic. Almost three of five of the adolescent girls, including both those
      who had and those who had not conceived, received a negative test result at a
      clinic before they ever became pregnant. By the age of 14 years, the probability
      of a negative test result was substantially greater than the chance of a positive
      test. Many presented for tests even though they were quite certain that they were
      not pregnant. CONCLUSIONS: Adolescent girls with a negative pregnancy test result
      may be an appropriate target group for intervention. One fourth of adolescent
      girls who have a negative pregnancy test may be identified by the health care
      system on that occasion in time to prevent early childbearing.

PMID- 8531306
TI  - Comparative mortality among US military personnel in the Persian Gulf region and
      worldwide during Operations Desert Shield and Desert Storm.
AB  - OBJECTIVE: To determine cause-specific mortality rates among US troops stationed
      in the Persian Gulf region and compare them with those of US troops serving
      elsewhere during Operations Desert Shield and Desert Storm. DESIGN: Retrospective
      cohort. POPULATION: US men and women on active duty from August 1, 1990, through
      July 31, 1991. MAIN OUTCOME MEASURES: Deaths occurring among all active-duty US
      military persons during the 1-year study period. Age-adjusted mortality rates
      among US troops stationed in the Persian Gulf region were compared with rates
      projected from mortality rates among troops on active duty elsewhere. RESULTS: A
      total of 1769 active-duty persons died during the study period, 372 in the
      Persian Gulf region and 1397 elsewhere. Of the 372 deaths in the Persian Gulf
      region, 147 (39.5%) occurred as a direct result of combat during the war, 194
      (52.2%) resulted from injuries not incurred in battle, and 30 (8%) resulted from
      illness. Twenty-three of the deaths due to illness were considered unexpected or
      cardiovascular deaths. Based on age-adjusted mortality rates observed among US
      troops on active duty outside the Persian Gulf region, 165 deaths from
      unintentional injury and 32 deaths from illness (20 of which were unexpected or
      cardiovascular) would have been anticipated among Persian Gulf troops.
      CONCLUSION: Except for deaths from unintentional injury, US troops in the Persian
      Gulf region did not experience significantly higher mortality rates than US
      troops serving elsewhere. There were no clusters of unexplained deaths. The
      number and circumstances of nonbattle deaths among Persian Gulf troops were
      typical for the US military population.

PMID- 8531307
TI  - Risk factors for HIV-1 seroconversion among young men in northern Thailand.
AB  - OBJECTIVE: To identify behavioral and sociodemographic risk factors for incident
      human immunodeficiency virus-1 (HIV-1) infection among healthy young men in
      northern Thailand. DESIGN: Men inducted into military service in northern
      Thailand in May and November 1991 were followed at 6-month intervals until
      discharge 2 years later. Trained nonmilitary interviewers identified risk factors
      for HIV-1 infection through interviews with the men. SETTING: Thirteen military
      bases in northern Thailand. PARTICIPANTS: A total of 1932 seronegative men, aged
      19 to 23 years (average age, 21 years) at enrollment, conscripted into the Royal
      Thai Army and Air Force from six upper-northern Thai provinces. MAIN OUTCOME
      MEASURES: Human immunodeficiency virus-1 seroincidence as determined through
      enzyme-linked immunosorbent assay and verified by Western blot, and univariate
      and multivariate analyses of risk factors related to HIV-1 incidence. RESULTS: A
      total of 85 men seroconverted to HIV-1 over the period of observation, giving an
      incidence rate of 2.43 per 100 person-years. Factors strongly associated with HIV
      1 seroconversion were frequency of visits to female commercial sex workers
      (CSWs), sex with men, and incident sexually transmitted diseases (STDs). High
      frequency of condom use showed a significant (P < .001) protective effect for HIV
      1 incidence among men with a history of recent sex with female CSWs in univariate
      analysis, but a multivariate model demonstrated no difference in HIV-1
      seroconversion rates by consistency of condom use. Multivariate analysis
      incorporating condom use showed that having sex with men (adjusted relative risk
      [RR], 2.59; 95% confidence interval [CI], 1.08 to 6.25), having sex with CSWs
      (adjusted RR ranged from 2.54 [95% CI, 1.81 to 3.58] to 2.74 [95% CI, 1.56 to
      4.81]), and incident STDs (adjusted RR, 2.38 [95%, CI, 1.31 to 4.32]) to be
      predictors of incident HIV-1 infection. Substance use was not associated with HIV
      1 seroconversion rates in multivariate analysis. CONCLUSION: The HIV-1 incidence
      in this cohort of young men appears to be primarily attributable to having sex
      with female CSWs. Condom use provided some protection, although not in
      multivariate analysis; however, condom use has previously been shown likely to be
      useful in preventing HIV-1 transmission. Thus, programs to increase effective
      condom use in brothels are essential. Efforts to extend condom use to non-CSW
      partners are especially needed. More effective prevention and treatment of STDs
      may also be necessary to decrease HIV-1 infection in this population.

PMID- 8531308
TI  - Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in
      patients with hypertriglyceridemia.
AB  - OBJECTIVE: To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3
      methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum
      triglycerides and other lipoprotein fractions in patients with primary
      hypertriglyceridemia, determine if atorvastatin causes a redistribution of
      triglycerides in various lipoprotein fractions, and assess its safety by
      reporting adverse events and clinical laboratory measurements. DESIGN: Randomized
      double-blind, placebo-controlled, parallel-group, multicenter trial. SETTING:
      Community- and university-based research centers. PATIENTS: A total of 56
      patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80
      mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL
      C) level of 3.07 mmol/L (118.7 mg/dL). INTERVENTIONS: Cholesterol-lowering diet
      (National Institutes of Health National Cholesterol Education Program Step I
      Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo. MAIN OUTCOME
      MEASURES: Percent change from baseline in total triglycerides for three dose
      levels of atorvastatin compared with placebo. RESULTS: Mean reductions in total
      triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4
      weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean
      reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and
      very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%,
      and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (
      16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and 
      3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In
      addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%,
      and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen.
      CONCLUSIONS: In atorvastatin treatment groups, total serum triglyceride levels
      decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups
      were statistically significant (P < .05) compared with placebo. Atorvastatin did
      not cause a redistribution of triglycerides but consistently lowered
      triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.

PMID- 8531309
TI  - Prognosis and outcomes of patients with community-acquired pneumonia. A meta
      analysis.
AB  - OBJECTIVE: To systematically review the medical literature on the prognosis and
      outcomes of patients with community-acquired pneumonia (CAP). DATA SOURCES: A
      MEDLINE literature search of English-language articles involving human subjects
      and manual reviews of article bibliographies were used to identify studies of
      prognosis in CAP. STUDY SELECTION: Review of 4573 citations revealed 122 articles
      (127 unique study cohorts) that reported medical outcomes in adults with CAP.
      DATA EXTRACTION: Qualitative assessments of studies' patient populations,
      designs, and patient outcomes were performed. Summary univariate odds ratios
      (ORs) and rate differences (RDs) and their associated 95% confidence intervals
      (CIs) were computed to estimate a summary effect size for the association of
      prognostic factors and mortality. DATA SYNTHESIS: The overall mortality for the
      33,148 patients in all 127 study cohorts was 13.7%, ranging from 5.1% for the
      2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the
      788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia
      etiology, ranging from less than 2% to greater than 30%. Eleven prognostic
      factors were significantly associated with mortality using both summary ORs and
      RDs: male sex (OR = 1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR = 0.5; 95%
      CI, 0.3 to 0.8), hypothermia (OR = 5.0; 95% CI, 2.4 to 10.4), systolic
      hypotension (OR = 4.8; 95% CI, 2.8 to 8.3), tachypnea (OR = 2.9; 95% CI, 1.7 to
      4.9), diabetes mellitus (OR = 1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR =
      2.8; 95% CI, 2.4 to 3.1), neurologic disease (OR = 4.6; 95% CI, 2.3 to 8.9),
      bacteremia (OR = 2.8; 95% CI, 2.3 to 3.6), leukopenia (OR = 2.5, 95% CI, 1.6 to
      3.7), and multilobar radiographic pulmonary infiltrate (OR = 3.1; 95% CI, 1.9 to
      5.1). Assessments of other clinically relevant medical outcomes such as morbid
      complications (41 cohorts), symptoms resolution (seven cohorts), return to work
      or usual activities (five cohorts), or functional status (one cohort) were
      infrequently performed. CONCLUSIONS: Mortality for patients hospitalized with CAP
      was high and was associated with characteristics of the study cohort, pneumonia
      etiology, and a variety of prognostic factors. Generalization of these findings
      to all patients with CAP should be made with caution because of insufficient
      published information on medical outcomes other than mortality in ambulatory
      patients.

PMID- 8531310
TI  - Ocular manifestations of AIDS.

PMID- 8531311
TI  - Curbside consultations. A closer look at a common practice.

PMID- 8531312
TI  - The patient-physician relationship. JAMA focuses on the center of medicine.

PMID- 8531313
TI  - Therapy for cytomegalovirus retinitis: still no silver lining.

PMID- 8531314
TI  - Patient-centered medicine. A professional evolution.
AB  - American medicine is in the midst of a professional evolution driven by a
      refocusing of medicine's regard for the patient's viewpoint. Historically,
      medicine has been largely physician centered, but physicians have begun to
      incorporate patients' perspectives in ways that increasingly matter. Some call
      this shift "patient-centered" care. In support of the view that this refocusing
      reflects a broad professional shift, we describe the evolution to patient
      centered care in many areas of medicine: patient care, health-related law,
      medical education, research, and quality assessment.

PMID- 8531315
TI  - Several new drugs shift direction of treatment and research for HIV/AIDS.

PMID- 8531316
TI  - Childhood aggression needs definition, therapy.

PMID- 8531317
TI  - Technologies described at radiology meeting someday may be deployed in war
      against cancer.

PMID- 8531318
TI  - From the National Institutes of Health.

PMID- 8531319
TI  - Wound botulism--California, 1995. From the Center for Disease Control and
      Prevention.

PMID- 8531320
TI  - Unexplained severe illness possibly associated with consumption of Kombucha tea-
      Iowa, 1995. From the Centers for Disease Control and Prevention.

PMID- 8531321
TI  - Work-related injuries associated with falls during ice storms--National
      Institutes of Health, January 1994. From the Centers for Disease Control and
      Prevention.

PMID- 8531322
TI  - A piece of my mind. Haying.

PMID- 8531323
TI  - [Natural interferon alpha for chronic myelogenous leukemia in the chronic phase:
      hematologic, cytogenetic and molecular response].
AB  - Twenty one patients with Philadelphia chromosome positive CML were treated with
      natural interferon alpha. All patients were in the chronic phase, 5 were
      untreated and 16 had been previously treated with busulfan or hydroxyurea. Eight
      patients in complete remission (CR) were given IFN subcutaneously at a dose of 5
      x 10(6) unit per day as maintenance therapy, whereas 13 non-CR patients were
      given 2. 5 approximately 10 x 10(6) units for remission induction. Doses and
      intervals of IFN were adjusted to maintain the WBC count below 5 x 10(9)/l, but
      additional drugs were given when the WBC count could not be controlled with IFN
      alone. Six out of 10 evaluable non-CR patients attained CR with IFN only and 4
      others achieved with additional drug. Cytogenetic responses were evaluated in 15
      patients. CCR, PCR and MCR were attained in 5, 2 and 1 patients respectively.
      Southern blotting method showed that the BCR gene rearrangement disappeared in 5
      out of 13 patients. Cytogenetic response rate was not different between untreated
      and previously treated patients, however it differed between patients with or
      without additional drug. The time to first cytogenetic effect was within 12
      months in almost all effective cases. Fever and general fatigue were seen in
      almost all patients. IFN administration was discontinued only patients with
      severe skin eruption (3 patients) and bone marrow aplasia (1 patient).

PMID- 8531324
TI  - [Morphological observation of a process of bone marrow hypoplastic formation in a
      case of aplastic anemia].
AB  - Bone marrow morphological change was consecutively analyzed form the disease
      onset to the formation of bone marrow aplasia in a patient with post-hepatitic
      aplastic anemia. In this case, the mean bone marrow cellularity and absolute
      numbers of erythroids and megakaryocytes were continuously higher than those in
      normal subjects for 3 weeks after the appearance of peripheral pancytopenia.
      During this stage, administration of recombinant human granulocyte colony
      stimulating factor (G-CSF) improved marrow myeloid hypoplasia and peripheral
      neutropenia. During the period in which the marrow cellularity transformed from
      hyperplasia to hypoplasia, the bone marrow showed a mixture of hyper-, normo- and
      hypocellular portions, and the decrease in the megakaryocytes was the faster than
      myeloid and erythroid cells. These findings indicate that (1) ineffective
      hematopoiesis might be present in the early stage of the disease, (2) G-CSF
      responsive granulocytic precursors remained during the early stage of the
      disease, and (3) the marrow aplasia progressed in the manner of aplastic nest
      formation during the period in which the marrow cellularity declined to
      hypoplasia. We experienced another case of aplastic anemia showing the same
      progress of bone marrow findings and speculated that this might be one of the
      ways of the progression of bone marrow hypoplastic formation in aplastic anemia.

PMID- 8531326
TI  - [Clinical subsets and phospholipid-dependent anti-beta 2-glycoprotein I
      antibodies in antiphospholipid syndrome].
AB  - Clinical significance of IgG phospholipid-dependent anti-beta 2-glycoprotein I
      (beta 2-GPI) antibodies in patients with antiphospholipid syndrome (APS) was
      studied. The subjects consisted of 14 patients with primary APS (PAPS) and 32
      with secondary APS based on SLE. IgG phospholipid-dependent anti-beta 2-GPI
      antibodies were examined by ELISA. Incidences of malar rash, arthritis, renal
      disorder, leucopenia, immunological disorder, and hypocomplementemia were
      significantly less frequent in patients with PAPS than in those with secondary
      APS based on SLE. However, sustained positive reactions of IgG anticardiolipin
      antibodies were found in 86% of patients with PAPS. Frequency of IgG phospholipid
      dependent anti-beta 2-GPI antibodies was significantly higher in patients with
      PAPS (100%) than in those with secondary APS (34%). Moreover, titer of IgG
      phospholipid-dependent anti-beta 2-GPI antibodies was significantly higher in
      patients with PAPS than in those with secondary APS. These data indicated that
      IgG phospholipid-dependent anti-beta 2-GPI antibodies are useful for identifying
      a subset in patients with APS as well as for studying the mechanism of thrombotic
      events in these patients.

PMID- 8531325
TI  - [Therapy related leukemia].
AB  - Eleven therapy related leukemias (TRL) who were hospitalized in the Department of
      Hematology and Chemotherapy, Kanagawa Cancer Center between October 1983 and
      December 1993 were identified. Six of the patients were males and five were
      females. Their median age was 62 years (range from 14 to 75). Three patients had
      previously received treatment for breast cancer and two patients for malignant
      lymphoma. The other patients had received treatment for lung cancer, urinary
      bladder cancer, gastric cancer, brain tumor, maxillary sinus cancer and
      macroglobulinemia, respectively. Seven patients had been treated with
      chemotherapy and four patients had been treated with chemotherapy and irradiation
      for the primary tumor. The TRL cases consisted of 8 acute non-lymphoid leukemias,
      two acute lymphoid leukemias and one hypoplastic leukemia, respectively. The
      status of primary tumors at the development of TRL was complete remission in ten
      patients and partial remission in one patient. Three of the 10 patients who
      received anti-leukemic therapy entered complete remission and the median survival
      time was 36 days (from 7 days to 489 days). One patient expired of pneumonia
      before he received anti-leukemic therapy. TRL patients showed poor response to
      chemotherapy and had poor prognosis. These data suggest that the use of reduced
      doses of carcinogenic drugs for primary tumors might be required to prevent the
      development of TRL.

PMID- 8531327
TI  - [Acquired amylase production induced by radiotherapy in a myeloma patient].
AB  - A 55-year-old patient with multiple myeloma (IgG-lambda) diagnosed in November
      1988 was admitted because of bone pain throughout the body. After plasmapheresis
      and several courses of chemotherapy, a massive tumor of the left thoracic wall
      involving the rib appeared. Radiotherapy was performed to ameliorate the severe
      chest pain, after which myelomatous pleural effusion appeared on the left side.
      The serum, urine and pleural effusion revealed increased activity of amylase of
      the salivary type. Amylase activity was also detected in the supernatant of
      myeloma cells cultured from pleural effusion. We reviewed 12 cases of ectopic
      amylase-producing multiple myeloma. All the cases except one have been reported
      from Japan, and hyperamylasemia in these cases was detected at diagnosis or
      during course of the illness. Moreover, cytogenetic analysis of myeloma cells of
      previous reports revealed structural abnormalities including chromosome 1, near
      the amylase gene locus. This case also showed t (1; 10) (q 21?; q 26) by
      examination of 8 metaphase derived from bone marrow. These observations suggested
      that ectopic amylase production was induced by irradiation to the plasmacytoma of
      thoracic wall.

PMID- 8531328
TI  - [Molecular evidence for a single clonal origin in a patient with multiple myeloma
      and non-Hodgkin's lymphoma].
AB  - A 49-year old man was admitted in November 1989, because of anemia, abnormal
      shadowing on chest X ray and hyperproteinemia. Biclonal gammopathy (IgG kappa +
      IgA kappa) was shown in serum, and Bence Jones protein in urine. The bone marrow
      examination showed an increased number of abnormal plasma cells (15.7%) and no
      evidence of lymphoma, A diagnosis of multiple myeloma (MM) was made. In April
      1990, while the patient was treated with the modified M2 regiman, swelling of the
      right cervical lymph node was observed. Lymph node biopsy revealed that he had
      non-Hodgkin's Lymphoma (:NHL, diffuse, mixed, B cell type). He was retreated with
      the CHOP regimen for both disease, but died of respiratory failure in October.
      1991. To establish the clonal origin of this case of concominant MM and B-cell
      NHL, the immunoglobulin gene rearrangements in his lymph node and bone marrow
      were analyzed. Southern blot analysis with the JH probe and Ck probe showed one
      common band and one different band in the two samples. Our data suggest that two
      B-cell malignancies may have arisen from a single B-cell progenitor.

PMID- 8531329
TI  - [Aplastic anemia complicated with secondary hemochromatosis after allogenic bone
      marrow transplantation].
AB  - We report a case of aplastic anemia complicated with secondary hemochromatosis
      after allogenic bone marrow transplantation (BMT). A 29-year-old man was
      diagnosed as having aplastic anemia at the age of 8. At the age of 28, BMT was
      performed from his HLA-identical sister. Total volume of blood transfusion before
      BMT was about 28,000 ml, and in three months after BMT was 8,000 ml. The
      transplantation was successful, but one month after BMT, dry eyes, skin
      pigmentation and hepatomegaly appeared. Serum bile duct enzymes and ferritin also
      increased remarkably. Moreover after thirteen months, glucose tolerance impaired
      seriously. Abdominal computed tomography (CT) revealed atrophic pancreas and an
      increased CT density in the liver and the tail of the pancreas. A large amount of
      iron deposition were also found in liver and stomach biopsy specimens. We
      concluded that diabetes mellitus was due to secondary hemochtomatosis in the
      present case. There is a possibility that tissue damage due to iron deposits may
      have been accelerated through BMT in this patient with a history of many blood
      transfusions.

PMID- 8531330
TI  - [The successful use of recombinant human erythropoietin therapy to anemia of
      granular lymphocyte proliferative disorder].
AB  - A 54-year-old man was admitted with fatigue. The peripheral blood count showed
      leukocytosis (9, 600/microliters), including 76% granular lymphocytes (GLs),
      which expressed CD2, 3, 8, 16 and HLA-DR, and anemia (hemoglobin 8.1 g/dl). He
      was diagnosed as having T cell type-granular lymphocyte proliferative disorder
      with anemia. Bone marrow examination revealed the involvement of 4.6% of GL and
      erythroblastopenia. A clonogenic assay of bone marrow cells revealed the decrease
      in erythroid colony formation in both CFU-E and BFU-E, but the number of
      erythroid colonies increased when CD8-positive cells were depleted from bone
      marrow cells and the number of erythroid colonies decreased again when CD8
      positive GLs were added. The supernatant of cultured CD8-positive GLs had no
      inhibitory effect on CFU-E and BFU-E colony formation. These suggested that CD8
      positive GLs suppressed the erythroid colony formation in this case. Treatment
      with 6,000 U/body of recombinant human erythropoietin (rh-Epo) subcutaneously
      three times a week was started and increased dose of 12,000 U/body of rh-Epo led
      to an increase in the hemoglobin level to 10.5 g/dl two months later. He has been
      treated with rh-Epo only.

PMID- 8531331
TI  - [Hemophagocytic syndrome with syndrome of inappropriate secretion of antidiuretic
      hormone (SIADH)].
AB  - A 69-year-old female was admitted to the hospital because of fever, hyponatremia
      and anemia. Laboratory data showed hemoglobin 8.6 g/dl, indirect bilirubin 1.9
      mg/dl and Na 122 mEq/l. Urine osmolality was elevated and urinary excretion of
      sodium was increased. Furthermore, antidiuretic hormone (ADH) level was elevated.
      Renal function and hormonal data were within normal limit. Therefore, she was
      diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH). On the other hand, bone marrow aspiration showed hemophagocytosis and
      the diagnosis of hemophagocytic syndrome (HPS) was also made. High dose
      prednisolone and pulse therapy of cyclophosphamide were administered,
      nevertheless high grade fever persisted. Fever alleviation was acquired by
      Etoposide. But she died of pneumonia. An autopsy revealed hemophagocytosis in
      bone marrow, lymphnodes and spleen, but malignant tumor was not detected. And
      hypophysis was intact. The pathogenesis of SIADH in this case was not clarified.
      This report is seemed to be the first case of HPS associated with SIADH.

PMID- 8531332
TI  - [Early relapse after peripheral blood stem cell transplantation in acute
      myelogenous leukemia with t(8;21)].
AB  - We report a 3-year-old boy with acute myelogenous leukemia, who relapsed very
      early after peripheral blood stem cell transplantation (PBSCT). He was admitted
      with a tumor in maxillar sinus and hemorrhagic diathesis and was diagnosed as
      having acute myelogenous leukemia with t(8;21). He achieved complete remission
      with etoposide, cytosine arabinoside and mitoxantrone. After 8 courses of
      consolidation therapy and marrow ablative chemotherapy, he received PBSCT. G-CSF
      was given from day 0 because of severe infection. WBC and platelete counts
      rapidly increased, however, from day 20 platelet count spontaneously decreased.
      Concomitantly bone marrow examination revealed the presence of blastic cells. RT
      PCR showed that the presence of AML 1/MTG 8 chimera mRNA in the cryopreserved
      PBSC samples. In vitro analysis also revealed that leukemic cells had G-CSF
      receptors and increased 3H-thymidine uptake in the presence of G-CSF. These
      findings strongly suggest that the reinfusion of leukemic cells in PBSC and the
      administration of G-CSF after PBSCT might be relevant to early relapse in this
      patient.

PMID- 8531333
TI  - [Essential thrombocythemia in transformation to smouldering megakaryoblastic
      leukemia with myelofibrosis].
AB  - Leukemic transformation in essential thrombocythemia (ET) is rare. We describe a
      patient with ET which transformed to megakaryoblastic leukemia with myelofibrosis
      after treatment with melphalan for 8 years. His course after transformation
      smouldered for 20 months without antileukemic chemotherapy. A 61-year-old man was
      referred by a local doctor to Niigata University Hospital due to nasal bleeding
      in June 1984. Complete blood count (CBC) was as follows; hemoglobin 12.4 g/dl,
      platelets 268.8 x 10(4)/microliters, and white blood cells 11,900/microliters,
      with differentials of 39% PMN, 1% basophils, 2% eosinophils, 4% monocytes, and
      13% lymphocytes. Bone marrow examination revealed hyperplasia of megakaryocytes
      without increase of reticulin fibers. Neutrophil alkaline phosphatase activity
      and karyotype of marrow cells were normal. ET was diagnosed. He was followed up
      by local doctor. The platelet count was controlled at a level of approximately 40
      x 10(4)/microliters with melphalan for eight years. In January 1992 he developed
      pain in his lower extremities. He was admitted to our hospital on May 29, 1992.
      CBC was as follows; hemoglobin 8.9 g/dl, platelets 14.3 x 10(4)/microliters, and
      white blood cells 3,500/microliters, with differentials of 25% PMN, 5% monocytes,
      28% lymphocytes, and 24% blasts. Bone marrow aspiration was unsuccessful and bone
      marrow biopsy revealed increases in fibroblasts and collagen fibers. Circulating
      blasts were positive for CD4, CD7, CD25, CD13, CD33, CD34, and HLA-DR and partly
      positive for CD41 and CD36. In ultrastructural cytochemistry blasts were positive
      for platelet peroxidase but negative for myeloperoxidase. Cytogenetic study
      revealed 46, XY, +der (1) t(1:7) (p11;q11) in all of five metaphases. He was
      diagnosed with megakaryoblastic leukemia accompanied by myelofibrosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8531334
TI  - [Multiple candida liver abscesses successfully treated by continuous intrahepatic
      arterial infusion of amphotericin B using a reservoir in a case with acute
      myelocytic leukemia (M2)].
AB  - A 49-year-old male was admitted with a diagnosis of AML (M2). One course of BHAC
      DM regimen induced complete remission. During the consolidation therapy, he
      developed marked pyrexia resistent to antibiotics. Ultrasonography and CT scan
      revealed multiple small liver abscesses, which suggested mycotic etiology. After
      unsuccessful treatment with intravenous administration of fluconazole, a
      percutaneous transhepatic intraportal administration of Amphotericin B (AMPH-B)
      (20 mg/day) was started, followed by the consolidation chemotherapy. When the
      first positive blood culture was obtained for Candida, a reservoir was embedded
      in the subcutaneous layer of the right iliac region and the intrahepatic arterial
      administration of AMPH-B (5 to 20 mg/day) by the Infusor (Baxter Healthcare
      Corporation), a portable, disposable drug delivery system that provides a
      constant drug flow, was started. The liver abscesses has almost disappeared when
      the maintenance chemotherapy was completed. The side effects of AMPH-B were
      negligible. This case suggests the usefulness of the intrahepatic arterial
      infusion of AMPH-B using an inplantable drug delivery system in patients with
      hematological malignancies developing intractable multiple fungal liver
      abscesses.

PMID- 8531335
TI  - [Neutropenia in patient with X-linked hyper-IgM syndrome].
AB  - The X-linked form of hyper-IgM syndrome (HIGM1) is a rare disorder characterized
      by the inability of B cells to undergo isotype switch by a deficiency of CD40
      ligand (CD40L) on activated T lymphocytes. The patients suffer from recurrent
      infections not only due to a lack of B lymphocyte activation but also due to
      defect of T lymphocyte functions. In addition, neutropenia is frequently
      accompanied by these symptoms. A patient with HIGM1, we experienced, suffered
      from recurrent infections and neutropenia. But he had a normal number of
      hematopoietic stem cell by the in vitro colony forming assay. CD34+ myeloid stem
      cell has been known to express CD40. We speculated by these facts that myeloid
      cell numbers are regulated by CD40-CD40L interaction.

PMID- 8531336
TI  - [CD5-negative B-cell chronic lymphocytic leukemia (B-CLL) associated with massive
      splenomegaly and without lymphadenopathy].
AB  - A 39-year-old male was referred to our hospital in June, 1993, because of
      leukocytosis. Physical examinations showed massive splenomegaly without any
      lymphadenopathy. The white blood cell count was 13,800/microliters with 87%
      morphologically mature lymphocytes. Bone marrow aspirate revealed
      hypercellularity with 67% lymphocytes morphologically similar to peripheral
      lymphocytes. The lymphocytes displayed monoclonal rearrangements of
      immunoglobulin genes and the phenotype of CD5-CD19+CD20+ CD21+ and Smlg+.
      Splenectomy was effective against neutropenia and thromboytopenia. The clinical
      and laboratory findings of this case were unusual compared to those of typical B
      CLL in massive splenomegaly, no lymphadenopathy and CD5-phenotype, suggesting the
      heterogeneity of B-CLL.

PMID- 8531337
TI  - [Successful treatment of splenomegaly and anemia by VP therapy in idiopathic
      myelofibrosis complicated with acromegaly: a case report].
AB  - Here we report a 65-year-old male patient with idiopathic myelofibrosis (IMF)
      accompanied with acromegaly. He was admitted because of anemia and splenomegaly.
      No favorable effects were observed when hydroyurea was administered. However, his
      symptoms were successfully treated by administration of vincristine and
      prednisolone (VP therapy), which is usually applied for choronic myelogenous
      leukemia in the accelerated phase. Therefore, VP therapy might be one possible
      for IMF. Since there have been several reports suggesting the possible
      association of hematological malignancies with acromegaly, we speculate that
      acromegaly was implicated in the initiation or progression of IMF in this case.

PMID- 8531338
TI  - [A case of Evans's syndrome in which thrombocytopenia and hemolysis was improved
      by Sairei-to].
AB  - A 51-year-old male diagnosed as having Evans's syndrome in 1991 was treated with
      25 mg of prednisolone, but his anemia and thrombocytopenia progressed. Thus, in
      November 1993, treatment was begun with Sairei-to, a Chinese herbal medicine
      consisting of several water-soluble plant extracts. Following administration of
      9.0 g/day of Sairei-to granules along with prednisolone, the platelet count
      increased from 6.1 x 10(4)/microliters to 12.3 x 10(4)/microliters after one
      week, while hemoglobin levels rose from 9.5 g/dl to 12.0 g/dl after three weeks.
      The patient maintained a good physical condition after the prednisolone dose was
      reduced, although Coomb's test and PAIgG levels remained positive. Sairei-to
      seems to be a promising therapeutic agent for steroid-resistant ITP and AIHA, and
      seems to have no side effects.

PMID- 8531339
TI  - [Epidemiology and pathogenesis of Sjogren's syndrome].
AB  - A nationwide epidemiological survey of Japanese Sjogren's syndrome (SS) patients
      was conducted in 1994 by the Research Committee on Epidemiology of Intractable
      Diseases and the Research Committee of Autoimmune diseases, Ministry of Health
      and Welfare, Japan. The total number of patients treated for SS in 1993, in
      Japan, was estimated as 17,000 (95% confidence interval 15,000-20,000). The
      estimated crude prevalence rates were 1.9 and 25.6 per 100,000 population in
      males and females, respectively. The ratio of female to male patients was 13.7.
      The peak of age distribution was in their fifties. New research trends to explore
      the pathogenesis of SS are also discussed here.

PMID- 8531340
TI  - [Classification criteria for Sjogren's syndrome--sensitivity and specificity of
      criteria of the Japanese Ministry of Health and Welfare (1977) and criteria of
      European community (1993)].
AB  - In patients with primary Sjogren's syndrome sensitivity of Japanese criteria was
      82.0% and specificity was 82.7%: sensitivity of European criteria was 73.3%, and
      specificity was 88.9%. In patients with secondary Sjogren's syndrome sensitivity
      of Japanese criteria was 74.5% and specificity was 85.7%: sensitivity of European
      criteria was 70.2%, and specificity was 89.3%. False-negative patients with
      decreased sensitivity of both criteria mostly showed a positive labial salivary
      gland biopsy without ovart dry mouth and dry eye symptoms. False-positive
      patients with decreasing specificity of both criteria were those who had only
      keratoconcunctivitis sicca without a positive labial salivary gland biopsy.

PMID- 8531341
TI  - [Clinical aspects and types of Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is a systemic as well as an organ-specific autoimmune
      disease, characterized by destructive lymphocytic infiltration of the salivary
      and lacrimal glands. We divided SS patients into three stages: stage I is
      glandular SS, stage II is extraglandular SS, and stage III is extraglandular SS
      with lymphoid malignancy. The lymphoaggressive nature of the disease appears to
      lead SS patients from stage I to II and from stage II to III. However, stage III
      patients made up only 5% of SS patients. Many patients remain stable in stages I
      or II for as long as 10 or 20 years. Therefore, we can assume that there are
      factors which trigger patients in stages I or II to progress to stages II or III
      and that only those patients who have such factors progress from stages I or II
      to stages II or III, respectively. Accumulation in the salivary glands or in the
      peripheral blood of B cells which have rearrangement of the RF-related germline
      gene Vg or over-expression of the bcl-2 gene in the lymphoepithelial lesion might
      be included among these factors.

PMID- 8531342
TI  - [Investigations of various animal models for Sjogren's syndrome].
AB  - Several animal models for studying immune-mediated sialadenitis include
      autoimmune-prone mice which develop lesions spontaneously, and non-autoimmune
      prone mice in which the lesions can be induced by various experimental
      manipulations. Autoimmune disease-prone mice such as NZB, NZB/WF1, MRL/lpr,
      SL/Ni, and NOD (non-obese diabetic) have been used as animal models for the
      investigation of Sjogren's syndrome in humans. We have previously demonstrated
      murine experimental systems in which autoimmune sialadenitis was induced in
      several strains of thymectomized mice, and developed spontaneously in certain
      strains of aged mice with H-2 restriction. We have recently established an animal
      model for primary Sjogren's syndrome in NFS/sld mutant mice bearing an autosomal
      recessive gene with sublingual gland differentiation arrest. A significantly
      higher incidence of autoimmune lesions in the salivary and lacrimal gland was
      found in female mice, and the anti-salivary duct autoantibodies were detected in
      sera from mice with autoimmune lesions. A preferential use of TCRV beta gene was
      detected in autoimmune lesions from the onset of disease, suggesting that TCR
      based immunotherapy is possible.

PMID- 8531343
TI  - [Current status and problems in the treatment of patients with Sjogren's
      syndrome].
AB  - Current status of treatment of patients with Sjogren's syndrome in Japan was
      reviewed. Although the number of patients with the syndrome has been increasing
      due to the recent progress in diagnosing and understanding of the disease,
      treatment of patients still remains unsatisfactory. However a wide variety of
      methods have become available in the management of patients who have significant
      dryness of eye and mouth. This includes artificial tear, artificial saliva,
      moisture shields of glasses, and many other medical and nonmedical preparations.
      All patients with sicca complaints should receive therapy of tear replacement and
      intensive oral hygiene. New potential therapeutic approaches for treatment of
      Sjogren's Syndrome was also reviewed.

PMID- 8531344
TI  - [Molecular mechanism on Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic
      infiltration into lachrymal and salivary glands leading to symptomatic dye eyes
      and mouth. Immunohistological studies have clarified that the majority of
      infiltrating lymphocytes around the lachrymal glands and labial salivary glands
      are CD4 positive alpha beta T cells. To analyze the nature of T cells in
      lachrymal glands and labial salivary glands, we examined TCR V beta genes of
      infiltrating T cells into both glands from SS patients, using PCR-SSCP and
      sequencing methods. The results showed the following two findings. 1) Some of T
      cells infiltrating in both glands expand clonally, suggesting that these cells
      proliferate by antigen-driven stimulation. 2) The common T cells accumulated in
      lachrymal and labial salivary glands. In conclusion, autoreactive T cells in lips
      and eyes should recognize the same epitopes of autoantigen in individual patients
      with SS. Further analysis on autoantigen using T cell lines from labial salivary
      glands supports the notion that Ro/SS-A 52 kD is a possible autoantigen
      recognized by autoreactive T cells.

PMID- 8531345
TI  - [Analyses of T cell clonality in mice with autoimmune sialoadenitis].
AB  - T cells are believed to be deeply involved in the pathogenesis of organ-specific
      autoimmune diseases. However, it remains unknown whether antigen-specific immune
      responses occur at the inflammatory sites in vivo. As a model of human Sjogren's
      syndrome, we investigated the T cell clonality of mice with autoimmune
      sialoadenitis, i.e. IQI/Jcl-(Saegusa et al), thymus grafted (TG) nude-(Taguchi et
      al), and MRL/lpr-SCID (Hayashi et al) mice; using RT-PCR-SSCP method. As a
      result, accumulations of distinct T cell clones were demonstrated in the salivary
      and lacrimal glands in these mice, without V beta restriction. Moreover, a part
      of the accumulating clones were commonly detected among multiple glands,
      suggesting the existence of a common and specific immune response probably toward
      autoantigen(s) expressed on the affected glands.

PMID- 8531346
TI  - [Aberrant expression of HLA-DR antigens on acinar and ductal epithelial cells of
      salivary glands in Sjogren's syndrome].
AB  - The major histocompatibility complex (MHC) class II antigens have been reported
      to play an important role in antigen presentation to T cells and influence the
      susceptibility to several autoimmune diseases, including Sjogren's syndrome (SS).
      In this paper, an aberrant expression of MHC class II antigens, especially HLA-DR
      antigens, on salivary glands of SS is described. HLA-DR antigens were
      immunohistochemically detected on acinar and ductal epithelial cells of SS
      patients but not those of healthy controls. This expression was observed in
      proximity to the periphery of dense lymphocytic infiltrates but sometimes not
      associated with lymphocytic infiltrates. These results are consistent with recent
      findings of HLA-DR antigen expression on target organs of various autoimmune
      diseases. Finally, we discussed a pathogenic role of HLA-DR antigens, aberrantly
      expressed on target organs of SS.

PMID- 8531347
TI  - [Cytokine mRNA expression in the labial glands of patients with Sjogren's
      syndrome].
AB  - It has been found that the pattern of cytokine mRNA expression was closely
      associated with the initiation and the progression of the disease process. The
      cytokine mRNA expression in the labial glands of patients with Sjogren's syndrome
      was examined by a PCR-based method. Th1 cytokines, such as IL-2 and IFN-gamma,
      were consistently detected in all patients examined, while Th2 cytokines, such as
      IL-4 and IL-5, were detected in some cases with strong B cell accumulation in the
      labial glands. These results suggest that Th1 cytokines are essential in the
      induction and/or maintenance of the disease, while Th2 cytokines are involved in
      the progression of the disease process. Other studies were also reviewed and a
      role of cytokines, produced by T cells and the target organ, was discussed.

PMID- 8531348
TI  - [Production and role of B cell growth factor (BCGF) in Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is characterized by polyclonal B cell hyperactivity in
      exocrine glands and peripheral blood. The number of CD20+ B cells is
      significantly increased in peripheral blood of twenty patients with SS in our
      study. LMW-BCGF (12 KD) cloned by Sharma in 1987 was reported to associate with
      DNA synthesis and to give the progressive signal of B cell cycle which develop G1
      stage to S stage. In our bioassay using Ks-3, F. 10 cells which respond only to
      BCGF and proliferate, T cells from SS patients showed increased production of
      BCGF, whether or not T cells were stimulated with PHA. It was suggested that BCGF
      may play an important role in the polyclonal activation of B cells in SS.

PMID- 8531349
TI  - [Autoantibodies in patients with Sjogren's syndrome and their clinical
      significance].
AB  - A variety of antinuclear antibodies were examined in 136 patients with primary
      Sjogren's syndrome, 131 patients with secondary Sjogren's syndrome and 139
      patients with various connective tissue diseases without Sjogren's syndrome.
      Among these, anti SS-A/Ro antibodies were found most frequently in secondary
      Sjogren's syndrome, whereas the incidence of anti SS-B/La antibodies, associated
      with anti SS-A/Ro antibodies, was highest in primary Sjogren's syndrome. In
      addition, anti RNP or anti centromere antibodies were also found in some patients
      with primary Sjogren's syndrome. Clinical characteristics related to individual
      antinuclear antibodies are also described.

PMID- 8531350
TI  - [Isotypes and subtypes of anti-SS-A and/or SS-B antibodies in different subgroups
      of Sjogren's syndrome].
AB  - Profiles of anti-SS-A/SS-B antibodies, including their isotypes and subtypes, in
      patients with primary Sjogren's syndrome (SS) were similar to those in SS
      patients with systemic lupus erythematosus (SLE), except for anti-SS-A52-Kd/60-Kd
      antibody profiles. The incidence and titers of these antibodies in SS patients
      with rheumatoid arthritis, however, were lower than those in primary SS or SS
      patients with SLE. It is suggested that IgA anti-SS-A/SS-B antibodies are
      produced in the salivary gland. In addition, IgG1 anti-SS-A antibodies were
      dominant in all groups of SS patients examined. The results indicate a
      preferential activation of Th2 helper T cells in SS.

PMID- 8531351
TI  - [Epitopes of the target proteins of anti-SS-A/Ro and anti-SS-B/La
      autoantibodies].
AB  - Anti-SS-A/Ro and anti-SS-B/La autoantibodies are diagnostically important in
      Sjogren's syndrome and systemic lupus erythematosus. However, the relationship
      between generation of these autoantibodies and the pathogenesis of the diseases
      remains to be solved. Several lines of autoepitope mapping of the target
      molecules revealed that multiple epitopes on the molecules were recognized by
      sera from patients with the diseases. This indicates that these autoantigens
      themselves drive the autoimmunity, that is, the molecules specific autoreactive T
      cells are activated. Further studies to elucidate how the autoreactive T cells
      become activated would be of help in understanding the pathogenesis of the
      diseases.

PMID- 8531352
TI  - [Sjogren's syndrome as a lymphoaggressive disorder; bcl-2 expression in
      lymphocytes infiltrated in salivary glands].
AB  - Sjogren's syndrome (SS) is a unique disease which develops a high incidence of
      lymphoproliferative disorder such as monoclonal gammopathy or malignant lymphoma.
      In order to elucidate the mechanism of the progression from polyclonal to
      monoclonal lymphoproliferation in SS patient, we analyzed the monoclonal nature
      and the expression of bcl-2 protein in the salivary glands. Formalin-fixed,
      paraffin-embedded salivary gland (labial salivary glands, 45; parotid glands, 6;
      submaxillary glands, 1) tissues or lung tissues (interstitial pneumonia in 2
      patients with SS) were serially sectioned and evaluated using the standard avidin
      biotin-peroxidase (ABC) technique. Murine monoclonal primary antibodies obtained
      from Dakopatts to B-cells (L26; CD20) and T-cell markers (UCHL1; CD45RO) and bcl
      2 protein were employed. The bcl-2-positive areas were stained with T and B cell
      markers in serially sectioned specimens. Lymphocytes forming the LEL were mostly
      composed of CD20-positive B-cells and these cells expressed bcl-2 protein. In the
      lip biopsy specimens, 36 of 45 patients showed small areas of bcl-2 expression in
      periductal lymphocytes. The expression of bcl-2 protein in the cells plays a
      crucial role in the cells escaping apoptotic cell death, living long and
      resulting in autoantibody production, and obtaining the increased risk of
      monoclonal proliferation of the cells. These findings provide further evidence
      for understanding the mechanism of monoclonal transformation from polyclonal
      lymphoproliferation in autoimmune reaction.

PMID- 8531353
TI  - [Expression of ductal Fas antigen in sialoadenitis of Sjogren's syndrome].
AB  - The expression of Fas antigen on ductal epithelial cells of sialoadenitis was
      examined in patient with Sjogren's syndrome and normal subject. In two patients
      with severe sialoadenitis, Fas antigen was strongly expressed on the ductal
      epithelial cells. In contrast, Fas antigen was not seen in minor salivary gland
      of normal subjects and of mild sialoadenitis cases. This finding suggests that
      Fas antigen may play a role in the pathogenesis of sialoadenitis in Sjogren's
      syndrome by providing a specific target for cytotoxic T cells expressing Fas
      ligand.

PMID- 8531354
TI  - [Analysis of Fas and bcl-2 expression on peripheral blood lymphocytes from
      primary Sjogren's syndrome].
AB  - The Fas antigen is the major trigger for apoptosis. In MRL/lpr mice, defects in
      Fas expression lead to autoimmunity and lymphoid accumulation, same as in the
      Sjogren's syndrome (SS). Bcl-2 protein is able to repress a number of apoptotic
      death. Therefore, we examined both Fas antigen and bcl-2 expression in peripheral
      blood lymphocyte (PBL) from SS patients. The rate of Fas+CD4+ PBL was
      significantly elevated (p < 0.01) in SS patients (n = 11) compared to normal
      controls (n = 15). Both Fas+CD3+ and Fas+CD8+ cells from SS patients showed a
      tendency to increase, whereas Fas+B cell was not different between each group.
      The percentages of bcl-2+ lymphocytes in SS patients were no different compared
      to the normal control. This study suggests that the increased expression of Fas
      may result in enhanced susceptibility to apoptosis.

PMID- 8531355
TI  - [Detection of retrovirus in salivary glands of patients with Sjogren's syndrome].
AB  - As similar symptoms and glandular pathology are observed in certain persons
      infected with human immunodeficiency virus (HIV) and human T lymphotropic virus
      type I (HTLV-I), a search was initiated for a possible retroviral etiology in
      Sjogren's syndrome (SS). Sera from 33% of 15 SS patients reacted against p24
      (gag) of HIV. Salivary gland (SG) biopsy specimens from 47% of the 15 SS patients
      contained an epithelial cytoplasmic protein, reactive with a monoclonal antibody
      to p24 of HIV. We also detected Mn2+ dependent, Mg2+ independent reverse
      transcriptase activity in the SG 3 of 10 SS patients. Target genes for HIV and
      HTLV-I were not found in any of the SG or peripheral blood mononuclear cells from
      SS patients. These data suggest the presence of an unknown retrovirus, similar to
      HIV, in the SG, which could contribute to the chronic inflammation of SS.

PMID- 8531356
TI  - [Exocrinopathy resembling Sjogren's syndrome induced by a murine retrovirus].
AB  - Recently, retrovirus is suggested to participate in the pathogenesis of Sjogren's
      syndrome (SjS). During the course of our study on mice infected with LP-BM5
      murine leukemia virus, we found SjS-like systemic exocrinopathy in those mice.
      This virus is known to induce murine acquired immunodeficiency syndrome (MAIDS)
      in sensitive strains of mice. Most cells infiltrating into the glands were
      composed of CD3+ T cells (CD4-dominant), Mac-1+ cells and also B220+ cells. The
      virus genome was detected in the submandibular glands by immunohistochemistry or
      by PCR and the retroviral particles were also detected by electron microscopy.
      This mice might become an animal model for SjS and provide us with valuable
      informations for analysing the mechanism of how a retrovirus could induce SjS.

PMID- 8531357
TI  - [HTLV-I infection in primary Sjogren's syndrome--epidemiological, clinical and
      virological studies].
AB  - The HTLV-I seroprevalence rate among the patients with Sjogren's syndrome (SjS,
      23.0%) was significantly higher than that among blood donors (3.4%). The age
      adjusted summary odds ratio of HTLV-I infection among SjS patients as compared
      with blood donors was 3.1. The etiologic fraction, i.e., the proportion of SjS in
      the study population that are attributable to HTLV-I infection, was estimated to
      be 17.6%. Titers of serum antibodies to HTLV-I in the seropositive SjS patients
      were significantly higher than those among healthy carriers. IgM class antibodies
      were commonly detected in sera of SjS patients. Salivary IgA class antibodies
      were common among seropositive SjS patients, but not in HAM patients or in
      healthy subjects. The findings strongly suggest that HTLV-I is involved in the
      pathogenesis of the disease in a subset of patients with SjS in endemic areas.

PMID- 8531358
TI  - [Expression of sequences homologous to HTLV-I pXIV gene in the labial salivary
      glands of Japanese patients with Sjogren's syndrome and pathogenesis].
AB  - To address the question of whether the human T cell leukemia virus type I (HTLV
      I) gene is associated with the etiology of Sjogren's syndrome (SS), RNA
      expression of HTLV-I gag, pol, env, and tax genes in labial salivary glands
      (LSGs) from SS patients who were seronegative for antibodies to HTLV-I was
      examined using RT-PCR method. The HTLV-I tax gene, but not the HTLV-I gag, pol,
      or env genes, was detected in LSG samples from 4 of 14 patients (29%). The
      nucleotide sequences of the HTLV-I pXIV region in these 4 patients' LSGs showed
      100% homology to the HTLV-I pXIV gene from the MT-2 cell line. In conclusion,
      these findings suggest that products encoding sequences homologous to the HTLV-I
      pXIV gene in SS patients' LSGs might be candidates for self-antigen and/or lead
      to activation of autoreactive T lymphocytes through trans-acting transcriptional
      activation.

PMID- 8531359
TI  - [Possible involvement of Epstein-Barr virus in the pathogenesis of Sjogren's
      syndrome].
AB  - Research into the role of Epstein-Barr virus (EBV) in the pathogenesis of SS has
      been a focus of interest for the past decade. The use of EBV as a probe for
      cellular and humoral immune responses has contributed to our current
      understanding of SS. However, it is still difficult to assign a role to EBV in
      the pathogenesis of SS. We have already demonstrated a) increased excretion of
      EBV in the saliva of SS, increased levels of EBV DNA in salivary gland biopsies
      of SS patients and spontaneous and massive production of transforming EBV in B
      cell lines established from SS patients. These data suggest that the reactivation
      of EBV might be deeply involved in disease perpetuation, polyclonal B cell
      activation and B cell malignancy in SS, even if it is not the primary cause.
      Recently, we examined the nucleotide sequence of the U2 region in EBV obtained
      from SS patients. The U2 region contains genes encoding EBNA-2, which plays an
      important role in B cell transformation and activation. In addition, studies on
      the breakdown of self-tolerance, and intriguing evidence supporting a potential
      role for infectious agents such as EBV and retroviruses also offer novel views of
      inflammation of salivary gland. This review will discuss recent advances in these
      subjects.

PMID- 8531360
TI  - [Immunological study of tissue-infiltrating lymphocytes in Sjogren's syndrome:
      virus specific T cell response].
AB  - The possible role of Epstein-Barr virus (EBV) in the pathogenesis of Sjogren's
      syndrome (SS) has been suggested. However, the evidence has been circumstantial
      and it is not known at all whether cellular immune responses to EBV are linked to
      the mechanism of the disease. Although the oligoclonal expansion of T lymphocytes
      in salivary glands of SS was indicated by some analyses of the T cell receptors,
      the corresponding ligands are unknown. The key question may be of whether this
      disorder involves virus specific immune attacks on the salivary glands being a
      site for EBV latency. We introduce here our functional study of the salivary
      gland-infiltrating T lymphocytes in patients with SS for detecting EBV specific
      memory T cells. The potential association of the state of EBV-specific CTL in the
      lesion with the reactivation of EBV will be discussed.

PMID- 8531361
TI  - [EBER-1 expression in salivary glands of Sjogren's syndrome].
AB  - EB virus-encoded small nuclear RNAs (EBERs) which present in large numbers during
      persistent infection, are known to stably bind to SSB/La antigen, leading to
      speculation that EBV may be involved in the pathogenesis of primary Sjogren's
      syndrome (1 degree SjS). Although studied by many investigators serologically,
      immunohistochemically and molecular biologically, this remains controversial. In
      situ hybridization study for EBER-1 showed positive hybridization in ductal
      epithelial cells in nine of eighteen salivary glands (SGs). Hybridization was
      more intense in ducts surrounded by infiltrating mononuclear cells (MNCs).
      Positive hybridization was also seen in infiltrating MNCs in eight 1 degree SjS
      SGs. These results indicate that EBV plays some pathogenic roles in some cases of
      1 degree SjS through induction of SSB/La antibody and impairment of lymphocytes.

PMID- 8531362
TI  - [Renal involvement in Sjogren's syndrome--interstitial nephritis and
      glomerulonephritis].
AB  - Renal involvement is well recognized extraglandular manifestation of primary
      Sjogren's syndrome (SS). The most common histopathological lesion is an
      interstitial lymphocytic infiltrate with tubular atrophy and fibrosis. The
      clinical presentation may be hyposthenuria, overt or latent distal renal tubular
      acidosis and less commonly Fanconi's syndrome. These tubular dysfunctions
      correlate with the presence of interstitial lymphocytes. Immunoregulatory
      alterations consisting of impaired T-cell function and B-cell hyperactivity
      probably play a pathogenetic role in the development of interstitial nephritis in
      SS. Glomerulonephritis in SS has been described in a limited number of case
      reports. Variant modes of pathogenesis have been proposed in these cases where
      glomerulonephritis has been associated with immune complex deposition and
      cryoglobulinemia.

PMID- 8531363
TI  - [Immunohistochemical identification of infiltrating mononuclear cells in
      tubulointerstitial nephritis associated with Sjogren's syndrome].
AB  - Using monoclonal antibodies, Immunoperoxidase analysis was performed on renal
      biopsy samples obtained from patients with Sjogren's syndrome associated with
      tubulo-interstitial nephritis. In all cases the interstitial infiltrates were
      predominantly CD5-positive T cells (mean 66%), whereas both B cell (CD19
      positive) and monocyte (CD15-positive) populations participated to a lesser
      degree. CD16-positive NK/K cells were rarely encountered. The CD4/CD8 ratio was
      consistently higher than 1.0 (mean 2.08). The lymphocyte which invaded the
      tubular epithelial cells to present a feature of tubulitis were CD8 positive,
      suggesting that they were cytotoxic T cells. These results were in general accord
      with those obtained in the salivary glands of patients with Sjogren's syndrome.
      It was thus concluded that the same immunological process was probably operative
      in the renal tubulointerstitial tissue as in the salivary glands to induced the
      characteristic tissue changes of Sjogren's syndrome.

PMID- 8531364
TI  - [T cell receptor repertoire of infiltrating T cells in the interstitial nephritis
      of patients with Sjogren's syndrome].
AB  - We examined the T cell receptor (TCR) repertoire of infiltrating T cells in the
      kidney, labial salivary glands (LSGs) and peripheral blood lymphocytes (PBLs) in
      Sjogren's syndrome (SS) patients with interstitial nephritis. The TCR V beta gene
      repertoire in kidney was more restricted compared with that in LSGs and PBLs. The
      TCR V beta 2 gene was predominantly expressed in six of seven kidneys (86%).
      Junctional sequence of TCR V beta 2 gene shows that some of these cells expanded
      clonally. The identical TCR clones in the kidneys were not detected in LSGs and
      the amino acid (Arg96) in the CDR3 region of V beta 2 gene was conserved
      specifically in kidneys. These findings suggest that T cells infiltrating in the
      kidneys from SS patients with interstitial nephritis identify different
      autoantigens from LSGs rather than superantigen.

PMID- 8531365
TI  - [Pulmonary function abnormalities and respiratory manifestations in Sjogren's
      syndrome].
AB  - The respiratory system is the target organ of many autoimmune collagen diseases.
      In patients with Sjogren's syndrome (SS), the respiratory disorders are also
      common manifestations. Tracheal and pleural manifestations have been described
      (Strimlan 1976; Constantopoulos 1985). In the older literature (Shearn 1979),
      pneumonia and pleurisy were often reported but did not seem to constitute any
      serious problem. The symptoms are frequent and clinically important. They can
      present in different ways from dry cough secondary to desiccation of
      tracheobronchial mucosa (xerotrachea) to dyspnea from airway obstruction or
      hypersensitivity of trachea. The common respiratory manifestation of SS is small
      airway disease, and the detection of this involvement requires clinical,
      roentgenological and respiratory functional tests. In particular, the respiratory
      functional test is useful for the diagnosis of respiratory disorders in patients
      with SS.

PMID- 8531366
TI  - [Clinical feature and pathology of airway disease in Sjogren's syndrome].
AB  - Airway disease of Sjogren's syndrome (SjS) has been studied since years ago. Many
      researchers have thought xerotrachea induced dry cough. Recently it was revealed
      that there was no xerotrachea but atrophic change and proliferation and growth of
      blood vessel. Various airway diseases of SjS have been reported, including
      bronchitis, bronchiolitis and follicular bronchiolitis. Rarely patients may lose
      their life for them. Patients of SjS without respiratory manifestations often
      show pulmonary function abnormalities. We compared pulmonary function of SjS and
      collagen disease without SjS. To our surprise, both of them show obstructive
      pattern with almost same frequency. Probably it means that obstructive airway
      diseases are not characteristic for SjS. Recently bronchial hyperresponsiveness
      in SjS is drawing the attention. Treatment and prognosis of the airway diseases
      in SjS have been not clarified, so further studies have to be piled up from now
      on.

PMID- 8531367
TI  - [Chronic pancreatitis and pancreatic dysfunction associated with Sjogren's
      syndrome].
AB  - Some pancreatic involvement was observed in Sjogren's syndrome (SS). Episodes of
      abdominal pain occurred infrequently in the course of SS, but there were some
      abnormal findings of the pancreatic functions and/or morphologic examinations.
      The level of serum amylase was affected by the destruction of both the pancreas
      and the salivary gland. Hyposecretion of bicarbonate in secretin test seemed to
      be characteristic in SS. ERP showed mild or moderate changes of the pancreatic
      duct, but their severities did not correlate with those of the salivary gland.
      Imaging of the pancreas tended to reveal definite abnormalities only in cases
      with an attack of pancreatitis. The roles of autoimmune mechanisms have been
      reported in pancreatitis associated with SS.

PMID- 8531368
TI  - [Autoimmune liver disease complicating Sjogren's syndrome].
AB  - Sjogren's syndrome (SjS) has been well known to complicate autoimmune liver
      diseases such as autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC).
      In addition, it has been recently described that chronic viral hepatitis type C
      could be accompanied by a sialadenitis resembling SjS. Among 98 patients with SjS
      at our clinic, 7 AIH, 1 PBC, and at least 11 hepatitis C virus (HCV) infection
      were noted. However, occurrence of SjS was not always associated with the
      severity of chronic liver diseases. Our present study suggested that three
      mechanisms might contribute to the pathogenesis of HCV-related SjS: 1) direct
      infection and proliferation of HCV in salivary glands, 2) molecular mimicry
      between HCV and salivary glands, and 3) formation of immune complex containing
      HCV. Further investigation would be indispensable to elucidate immunological
      systems to regulate these phenomena.

PMID- 8531369
TI  - [Primary biliary cirrhosis in patients with Sjogren's syndrome].
AB  - Primary biliary cirrhosis (PBC) is one of the most frequent hepatic diseases
      associated with Sjogren's syndrome (SS), its reported incidence ranging from 3%
      to 9%. There is much association between SS and PBC in the pathogenesis. In both
      diseases, autoimmunity seems to be directed toward the ductal epithelial cells.
      Epstein Barr Virus may contribute to PBC, as well as SS. PBC associated with SS
      tends to be asymptomatic and to be in an early stage in histologically.
      Antimitochondrial antibody (AMA) is the most sensitive indicator of PBC in
      primary SS. When SS patients have an elevated alkaline phosphatase level, it is
      necessary to examine AMA and to perform liver biopsy.

PMID- 8531370
TI  - [Atrophic gastritis in Sjogren's syndrome].
AB  - In patients with Sjogren's syndrome (SJS), it has been found that chronic
      atrophic gastritis is often associated with low HCl secretion or achlorhydria.
      However, the role of autoimmune injuring mechanism in the pathogenesis of the
      atrophic gastritis in SJS is unclear. In recent studies, Helicobacter pylori (HP)
      infection is accepted as the major cause of chronic gastritis. In our studies, HP
      infection was present in the half of SJS patients with atrophic gastritis. We
      also determined HP specific IgG antibody levels by enzyme-linked immunosorbent
      assay (ELISA). In SJS patients with gastric inflammatory cell infiltration, the
      IgG levels were high. We determined gastric parietal cell antibody (PCA) levels
      by ELISA, using a recombinant fusion protein of the alpha subunit of gastric H+,
      K(+)-ATPase. Our observation suggests that atrophic gastritis in SJS is caused by
      HP infection associated with gastric mucosal injury due to PCA.

PMID- 8531371
TI  - [Clinical and pathological features of Sjogren's syndrome associated with
      autoimmune thyroid diseases].
AB  - Sjogren's syndrome (SS) is a chronic inflammatory disease of the exocrine glands
      accompanied by mononuclear cell infiltration. The histopathological features of
      the salivary and lacrimal glands of SS resemble those of the thyroid glands of
      autoimmune thyroiditis (chronic thyroiditis; CT). In addition, both SS and CT
      frequently recognized in the patients with other organ-specific or systemic
      autoimmune diseases (collagen-vascular diseases; CVD). We analyzed the incidences
      of CT among patients with SS or CVD, and compared clinical, immunological and
      endocrinological profiles between the SS patients with and those without CT. CT
      was the most frequent organ-specific auto-immune disease recognized in both
      primary and secondary SS patients. The thyroid disease similarly associated with
      CVD patients, regardless of the presence of SS. Several studies have also
      suggested that subclinical diseases are frequent in both CT and SS patients. The
      clinical and immunohematological features were almost identical between SS
      patients with and those without CT. Furthermore, the clinical, serological and
      endocrinological profiles of thyroid disease were very similar between SS
      patients with CT and CT patients without SS. These results indicate that CT and
      SS are independent autoimmune diseases, and the thyroid involvement observed in
      patients with primary or secondary SS is not an extraglandular manifestation of
      SS.

PMID- 8531372
TI  - [Cutaneous manifestations of primary Sjogren's syndrome].
AB  - Cutaneous manifestations including purpura, annular erythema and pernio-like
      erythema are one of the extraglandular findings of primary Sjogren's syndrome
      (SS). Histopathologically, inflammatory vascular lesions are frequently detected.
      Two types of annular erythema, edematous and atrophic types, can be seen.
      Histopathologically, atrophic annular erythema is hardly distinguished from SCLE.
      Skin lesions of primary SS, especially purpura and edematous annular erythema,
      are related with anti-SS-A/Ro and SS-B/La antibodies. Some of the cutaneous
      manifestations develop both in primary SS and lupus erythematosus and anti-SS
      A/Ro and SS-B/La antibodies may play an important role in the development of
      these cutaneous lesions.

PMID- 8531373
TI  - [Recurrent annular erythema--cutaneous manifestation of Sjogren syndrome with
      anti SS-A (Ro) and anti SS-B (La) antibodies].
AB  - Eight cases of Sjogren syndrome (SjS) with anti-SS-A and anti-SS-B antibodies are
      reported. They developed erythema annulare centrifugum-like annular erythema
      which mainly appeared on the face. Laboratory tests showed similar serologic
      changes. RA factor, speckled type antinuclear antibody, anti SS-A & SS-B
      antibodies (DID & ELISA) were observed but complements and anti-double stranded
      DNA antibodies were not detected. In spite of mild sicca symptoms, sialogram, lip
      biopsy, Shirmer test and Rose Bengal staining showed typical changes of SjS. It
      is considered that the recurrent annular erythema is a specific skin
      manifestation of SjS with anti SS-A/SS-B antibodies.

PMID- 8531374
TI  - [Neuro-psychiatric involvement in primary Sjogren's syndrome].
AB  - Neuro-psychiatric involvement in primary Sjogren's syndrome (PSJS) has been
      summarized according to the literature. Sjogren's syndrome is an autoimmune
      disorder with a predilection for multi-system involvement. Recently, disorders of
      the peripheral nervous system (PNS) and central nervous system (CNS) in PSJS, as
      well as, other organ involvement has been reported increasingly. However, CNS
      involvement, including the symptoms mimicking multiple sclerosis in PSJS is a
      controversial issue. There is discrepancy in the frequency of CNS involvement in
      PSJS among investigators. As for psychiatric manifestations in PSJS, descriptions
      have been made by many investigators. Depression and anxiety are the most common
      psychiatric manifestations in PSJS. About 10% of the patients with SJS have a
      neuropathy which tends to predilect for trigeminal nerve involvement. Further
      investigations elucidating the mechanisms of neuro-psychiatric involvement in
      PSJS is required.

PMID- 8531375
TI  - [Sensory ataxic neuropathy associated with Sjogren's syndrome].
AB  - One tenth of patients with Sjogren's syndrome (SS) is associated with peripheral
      neuropathy. Trigeminal neuropathy, mononeuropathy multiplex, sensory neuropathy,
      distal sensory neuropathy, ataxic sensory-autonomic neuropathy have been
      described as the neuropathy associated with SS. However, some of them secondary
      occur associated with the vasculopathy due to rheumatoid arthritis, systemic
      lupus erythematodes etc combined with SS. We demonstrated the clinico-patho
      physiological features and spinal MRI findings of patients with primary SS in
      whom the sensory ataxia and autonomic dysfunctions were the predominant symptoms.
      The underlying pathology was lymphocytic (T cells) infiltration to the dorsal
      root ganglia with sensory neuronal degeneration. These findings have identified
      as association between SS and sensory ataxic neuropathy.

PMID- 8531376
TI  - [Sjogren's syndrome associated with non-Hodgkin's lymphoma].
AB  - Sjogren's syndrome (SS) is characterized by an increased risk of development of a
      non-Hodgkin's lymphoma (NHL). In this paper, the clinical, histological and
      molecular biological topics, with a brief account of two cases of NHL, in SS are
      discussed. Low grade NHL, typically monocytoid B cell lymphoma related to mucosa
      associated lymphoid tissue (MALT) lymphoma, is the topic of NHL in SS. B cell
      clonal expansion has been detected by DNA analysis of immunoglobulin gene in non
      lymphoma patients, as well as, in NHL patients in SS. Molecular biological
      analysis, especially detection of fusion gene of IgH and bcl-2, t(14;18), using
      PCR method, can help to detect early onset of NHL in SS. A better understanding
      of NHL in SS is needed to develop a co-operative research of large mass study.

PMID- 8531377
TI  - [Lymphoproliferative disorders in patients with Sjogren's syndrome--Vg gene
      rearrangement and expression of bcl-2 protein].
AB  - Sjogren's syndrome (SS) is a unique disease which develops a high incidence of
      lymphoproliferative disorders (LPD) such as monoclonal gammopathy or malignant
      lymphoma. In order to elucidate the mechanism responsible for the emergence of
      monoclonal B cell proliferation at the site of a chronic autoimmune reaction, the
      rheumatoid factor (RF) related germline gene Vg and expression of the bcl-2 gene
      in the lymphoepithelial lesion (LEL) were studied. Predominant usage of the Vg or
      Vg-like genes was found in the peripheral blood leukocytes in SS patients and
      abundant expression of bcl-2 protein in the lymphocytes in and around the LEL
      were observed. These results suggest that RF clones were activated resulting into
      monoclonal proliferation and overexpression of bcl-2 protein play a role allowing
      the cell to escape a apoptotic cell death resulting into the increased risk of
      monoclonal proliferation in SS patients.

PMID- 8531378
TI  - [Conversion of zinc finger protein to artificial site-specific nuclease:
      application to chromosome mapping and sequencing].
AB  - Zinc finger motif is a novel DNA binding motif characterized by the unique role
      of zinc; the protein folding and the DNA binding ability are governed by the
      coordination of a zinc ion. In C2H2-type zinc finger, two cysteines and two
      histidines contribute to form a globular domain through zinc coordination. The
      zinc finger of C2H2-type gives promise of recognition for any DNA sequences
      because of its recognition mode. A C2H2-type zinc finger protein Sp1 has been
      converted into artificial site-specific nuclease with an attached Ni-based DNA
      cleavage unit (Gly-Gly-His). This protein cleaved DNA at a single site near the
      Sp1 recognition sequence. The zinc finger-based nuclease is applicable to
      chromosome mapping and sequencing.

PMID- 8531379
TI  - [The molecular mechanism of costimulatory signal for T cell activation].
AB  - The initiation of T cell responses against antigens requires two distinct
      signals. The first, the essential signal is the engagement of T cell receptor to
      antigen peptide in the context of MHC molecules on antigen presenting cells
      (APC). The presence of the second signal (costimulatory signal) determines
      whether responding T cells to be fully responsive or to be anergic (antigen
      specific nonresponsiveness). There are numbers of such costimulatory
      receptor/ligand pairs including B7/CD28: CTLA4, VCAM-1/VLA4, ICAM-1/LFA-1,
      HSA/unknown, and LFA-3/CD2. Among those ligand receptor pairs, B7/CD28 pathway is
      chosen and the molecular mechanism how T cell responses are regulated by B7/CD28
      is discussed.

PMID- 8531380
TI  - [Structure and function of P-glycoprotein in antitumor agent resistance;
      implication for clinical setting].
AB  - Resistance of tumors to a variety of chemotherapeutic agents presents a major
      problem in cancer treatment. The gene responsible for multidrug resistance,
      termed mdr1, encodes a membrane glycoprotein (P-glycoprotein) that acts as a pump
      to transport various cytotoxic agents. The P-glycoprotein has been shown to bind
      anticancer drugs and several resistance-reversing agents including calcium
      channel blockers, and to be an ATPase. The P-glycoprotein was found to function
      in blood-brain barrier. The implication of the P-glycoprotein in relation to
      therapy is discussed.

PMID- 8531381
TI  - [Hospital management and the role of clinical microbiology laboratory for
      preventing nosocomial infection].
AB  - Nosocomial infection is a serious issue in the hospital management.
      Countermeasures for this issue have been discussed from various points including
      clinical and laboratory medicine, nursing as well as hospital administration.
      This issue is of great importance to those of us medical practitioners, who
      engage in diagnosis and treatment of infectious diseases. The role of clinical
      microbiology laboratories for prevention of nosocomial infection includes
      performing epidemiological survey, giving information and education, and training
      and instruction to medical staff. In order to instruct and inspect the
      countermeasures against nosocomial infection, it is necessary to have a dedicated
      team in the hospital. We have organized an infection control team(ICT) to collect
      information and offer training and instruction regarding nosocomial infection.
      The ICT activities include 1) inspecting if the nosocomial infection control
      manual is followed correctly, 2) reporting the results of epidemiological survey
      regarding nosocomial infection, 3) offering the information regarding
      antimicrobial agents and disinfectants, 4) offering the information regarding the
      isolation of microorganisms in the hospital and their antimicrobial
      sensitivities, 5) cost calculation for nosocomial infection control.

PMID- 8531382
TI  - [Strategy for getting many experts in clinical pathology].
AB  - Laboratory tests are indispensable to rational medical care and will play more
      and more important roles in clinical and preventive medicine. However, progress
      in laboratory medicine is so rapid that many clinicians feel difficulty in using
      laboratory tests properly. To keep the quality of medical care high in terms of
      medical science, many well-trained clinical pathologists and medical
      technologists are needed to help clinicians use laboratory tests properly. To
      obtain enough experts in the area of clinical pathology, we should pave the way
      to clinical pathology for young ambitious people and make efforts to help both
      young clinical pathologists and clinical technologists feel themselves playing an
      important role in medical care.

PMID- 8531383
TI  - ["Quick Return Service" of the surgical pathology].
AB  - The "Quick Return Service" of laboratory information would be the service for
      patients and clinicians that supply the laboratory information the instance that
      the specimens and the requests of laboratory examinations are accepted by the
      laboratory on the basis of the hospital information system (HIS) and the high
      speed hospital transportation system of the specimens. Is the "Quick Return
      Service" of the pathological diagnosis possible and necessary? This question led
      the author to review the technical environments of the pathological diagnosis,
      especially of the frozen section diagnosis through our experience at the surgical
      pathology division of the Department of Laboratory Medicine of National Defense
      Medical College (NDMC) Hospital. Through the review, it appears that the
      supporting system for surgical pathologists to frozen section diagnosis ("Quick
      Return Service") is essential. Pathologists often need clinical and radiological
      information at the pathological diagnosis. For quick gaining of the information
      by surgical pathologists on the "Quick Return Service", the efficient HIS
      including hospital PACS (picture archiving and communication system) is
      necessary. Standardization and quality assurance of images of frozen section are
      also necessary. The technical environments of telepathology are developing. The
      interinstitution consultation through the telepathology will be the indispensable
      help for the "general" surgical pathologists confronting the problematic cases in
      the small hospitals that are deficient of pathologists. With the help of staff of
      the surgical pathology division of the NDMC hospital and the technologists of
      Mitsubishi Electronics, Co, the author has tried to develop the archiving system
      of frozen section pictures on the digital image management system.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8531384
TI  - [Rapid cytology].
AB  - The indications for and limitations of rapid cytology were discussed, and
      intraoperative cytology in combination with frozen section histology was
      reviewed. During the past 14 years, intraoperative cytology and frozen section
      histology were simultaneously performed in 1,987 cases of various diseases and
      organs. A discrepancy between the cytologic and the frozen section diagnoses was
      noted in 39 (2.0%) instances, and the combined use of cytology and histology was
      concluded to be useful for correct intraoperative diagnosis owing to their
      supplementary effect. A rapid preparation and staining technique for
      intraoperative cytology was described.

PMID- 8531385
TI  - [Genetic analysis for hereditary disorders].
AB  - Many genetic abnormalities responsible for hereditary disorders has been
      localized on chromosomes by positional cloning. Identification of RFLP and VNTR
      markers facilitated the process. Once mutations have been fully characterized,
      prenatal or presymptomatic diagnosis can be easily made by using polymerase chain
      reaction (PCR). Since no curable treatments are available for most of hereditary
      disorders, the following premises should be well understood when performing
      genetic analysis; 1) association of the mutation to look at and the hereditary
      disorder must be clearly demonstrated, 2) patients and their families must have
      opportunities to have counseling on the disease by experts in the field. 3)
      everybody must respect the will of patients and families to have or not to have
      genetic analyses, 4) every information should be securely kept and privacy of
      patients and families must be fully protected, and 5) genetic analysis procedures
      must be accurate and reliable. Recently, we characterized dysfibrinogenemia
      Matsumoto I. The proband was asymptomatic and only screening coagulation tests
      revealed mild prolongation of prothrombin time. Its functional level was as low
      as 5% of its immunologically determined level. Genetic analysis identified an
      amino acid substitution of gamma 364Asp-->His. Living-related liver
      transplantation performed to treat a patient with familial amyloid polyneuropathy
      is briefly described in this article.

PMID- 8531386
TI  - [Quick Return Service in endocrinological tests].
AB  - It is important to measure certain hormones to make a diagnosis as quickly as
      possible. We inquired the needs of quick return services (QRS) in the field of
      endocrinology. First, we sent questionnaires to 86 endocrinologists in Japan
      (recovery 83%). About 20.2% of the endocrinologists wanted to receive QRS for the
      diagnosis of thyroid disorders. However, less than 10% of the specialists wanted
      to receive QRS on pituitary hormones, sex hormones and many other hormones. These
      responses were as expected. It is clear from our experience reported previously
      that the appropriate choice of a commercially available kit is essential if
      serious errors are to be avoided. Accurate and precise results are much more
      important than receiving QRS.

PMID- 8531387
TI  - [The assessment of quick turnaround service in clinical laboratories].
AB  - The quick turnaround service of laboratory data has been a basic and fundamental
      service of clinical laboratories. To realize this service, there are three basic
      requirements in the hospital and laboratory information systems. The first is
      cooperation with the hospital information system providing bar-coded label
      sampling system and test requisition from the information system terminal. The
      second is real time quality assurance system fully supported from the laboratory
      information system. The third is random and sequential automated analyzer
      supported by the bar-code system. In 1994, we set up an automated system in our
      clinical laboratories. The effect of the quick turnaround service of reporting
      was analyzed and is discussed herein. Employing this system, the quick turnaround
      service system was established for 31 items of biochemistry, glucose, Thrombo
      test and complete cell counting of hematology. Furthermore, these items were
      available within 30 minutes before medical consultation. Effective sample
      conveying system, quick sample preparation without clotting and arrival
      information system of laboratory data as a mailing system are further
      requirements for this quick turnaround service system.

PMID- 8531388
TI  - [The Quick Return Service of electroencephalogram].
AB  - Because electroencephalography (EEG) examinations take time and numerous channels
      are used, they generate an enormous volume of data. Vast amounts of space would
      be required to store the data on shelves and in storage rooms, and a great deal
      of time and labor would be needed to retrieve the data and use it again. We
      developed an EEG optical disk filing system to solve such problems. With this
      system display terminals are set up in the various outpatient departments which
      often request EEG examinations, i.e., the neurology department, psychiatry
      department, and pediatric department, making it possible to search and display
      EEG waveforms, the content of EEG reports, etc., stored on the optical disks at
      any time. Using such functions patients can be examined without having to send
      for charts and EEG paper-output waveforms, which is troublesome and time
      consuming, and contributes to shortening examination time.

PMID- 8531389
TI  - [Rapid detection and identification of mycobacteria by the PCR assay based on the
      co-amplification of the gene IS6110 and groEL].
AB  - In definite diagnosis of mycobacterial infection, prompt and adequate
      differential diagnosis leads to an appropriate treatment. We developed and
      evaluated a PCR assay based on co-amplification of the insertion sequence IS6110
      and groEL gene that are species-specific for Mycobacterium tuberculosis complex
      and genus-specific, respectively. The detection limit of the assay system for
      cultured M. tuberculosis was 2 cells/ml, as compared with 200 cells/ml by culture
      onto Ogawa's medium. To assess the value of the assay in routine laboratory
      works, the results obtained by PCR were compared with those by standard
      microbiological methods for 758 specimens collected for the examinations of
      mycobacterial infection. The PCR system for detection of mycobacteria gave
      overall positive rate of 27.6% (209/758), as compared to 6.1% (46/758) by smear
      and 7.7% (58/758) by culture onto Ogawa's medium. Sensitivity and specificity
      were 97.8% and 97.3%, respectively, for the IS6110 and groEL gene for detection
      of M. tuberculosis complex; 91.7% and 80.3%, respectively, for only the groEL
      gene for detection of atypical mycobacteria. The PCR assay based on co
      amplification of the IS6110 and groEL gene would be useful for diagnosis of
      mycobacterial infections, allowing not only more sensitive detection of
      mycobacteria but also rapid discrimination between M. tuberculosis complex and
      atypical mycobacteria. This assay would help to eliminate time-consuming
      confirmation, and to avoid both unnecessary treatment and hospitalization of the
      patient.

PMID- 8531390
TI  - [Adenosine deaminase isoenzymes in patients with Graves' disease].
AB  - CD26, the T cell activation antigen, is identical to the ADA binding protein and
      is considered to interact with ADA to activate the T cells on the surface.
      Therefore, we examined the activity of serum ADA isoenzymes in patients with
      Graves' disease in whom CD26 presented T cells were increased. The activities of
      total ADA and ADA2 were significantly higher in Graves' disease than normals. We
      also observed that the levels of soluble interleukin-2 receptor (sIL-2R) and
      neopterin, markers of T cell activation, were significantly higher in Graves'
      disease. The correlation coefficients among ADA2, neopterin, and sIL-2R were
      significantly high (p < 0.001). Among these parameters, only sIL-2R was
      correlated with the thyroid hormones. ADA2 activity was considered to reflect the
      activated state of T cells and to be, independent of the thyroid hormone levels.

PMID- 8531391
TI  - [Methicillin-resistant Staphylococcus aureus forming the fried egg appearance
      colonies isolated from a patient with septicemia].
AB  - Slower growing and peculiar colonies, "fried egg" appearance, of different sizes
      were temporally grown on a sheep blood agar plate from a clinical blood sample
      obtained from a patient with mediastinitis due to infection by methicillin
      resistant Staphylococcus aureus (MRSA) following the graft replacement of
      thoracic aorta. The organisms revealed morphologically characteristic "fried egg"
      appearance, mainly Gram-positive cocci including some Gram-negative cells and
      cell-debris, catalase test positive and coagulase test positive as well as having
      the identical profiles for S. aureus on biochemical examination with VITEK
      Systems. The rough surfaced cell walls with unequal thickness of the organisms
      were observed in an electronmicroscope. According to these bacteriological
      studies, the organisms were identified as a mutant of S. aureus which had many
      similarities to staphylococcal L-form. Being resistant to oxacillin, instead of
      methicillin susceptibility test, and possessing a mecA gene, the organisms were
      confirmed to belong to MRSA. It is likely that this mutant of S. aureus was
      induced by a long term medication of sulfamethoxazole-trimetoprim, since the
      patient had been receiving the drug during 5 weeks when the colonies were first
      detected.

PMID- 8531392
TI  - [Identification of Capnocytophaga species by microplate hybridization method, and
      its restriction endonuclease digestion patterns].
AB  - Because differentiation of Capnocytophaga on a species level has been reportedly
      proved impossible, we used a microplate hybridization method to identify three
      Capnocytophaga species. Photobiotin labeled DNAs from clinical isolates were
      added to the wells of a microdilution plate in which reference DNA had been
      immobilized. After 2 h of hybridization at 40 degrees C, hybridized DNAs were
      quantitatively detected with peroxidase-conjugated streptavidin and the
      substrate, tetramethylbenzidine. Of the 22 strains of Capnocytophaga species, 6
      strains were identified as C. sputigena, 8 strains as C. gingivalis, and 8
      strains as C. ochracea. Genomic DNAs from 25 strains of Capnocytophaga were
      treated with restriction endonuclease of HindIII, HaeIII, and HinfI. Nine strains
      of C. gingivalis showed no bands by the conventional electrophoresis of digested
      DNA. However, twelve strains (6 strains of C. sputigena and 6 strains of C.
      ochracea) revealed bands by the electrophoresis of HinfI-digested DNA, and ten
      isolates had its own digestion patterns, indicating the presence of genetic
      variation. On the other hand, two strains of beta-lactamase-producing C.
      ochracea, one from blood and one from throat swabs obtained from a patient with
      acute leukemia, were classified as the same isolate by the identical digestion
      pattern and by the antimicrobial susceptibility test results, which strongly
      suggested that the oral lesion is the portal of entry into the blood.

PMID- 8531393
TI  - [The measurement of blood lactate concentration and its age change in days on
      healthy infant].
AB  - We measured the lactate concentration in whole blood of healthy infant with use
      of the recently developed assay system consisting of an enzyme-coated electrode
      and a small meter. The mean values of blood lactate concentration at each age in
      days were not showed the significant difference between male and female infants.
      The trace of lactate concentration change in days showed the peak at the age in 1
      days and then, gradually decreased to the almost constant level at the age in 6
      days after. At the age in 6-7 days, the concentration mean values of infants,
      born in 38-40 gestational weeks were lower than that of 37 and 41 weeks one. It
      was assumed by mathematically that these equilibrium constant level of the
      lactate concentration in early neonatal period was arrived at 6.20 days and the
      equilibrium level was estimated to 1.29 mmol/l. As the results, the normal ranges
      were calculated to the value of 0.49-3.95 mmol/l as initial (age in 0-3 days) and
      that of 0.29-2.92 mmol/l as final (age in 6-7 days) period, by the truncation
      method, respectively.

PMID- 8531394
TI  - [A case of acute myelogenous leukemia accompanied with myelofibrosis and
      megakaryocyte-like giant bizarre blasts].
AB  - A 45-year-old man was admitted with high fever and leukocytosis in August 1993.
      The diagnosis of acute myelogenous leukemia (AML; M2) was made on the basis of
      morphological, cytochemical and immunological characteristics of the blasts in
      the bone marrow. The induction therapy with BHAC, daunorubicin, 6-MP was
      unsuccessful in achieving remission; the bone marrow biopsy specimen revealed the
      proliferation of the remaining leukemic cells and massive fibrosis accompanied
      with unusual megakaryocyte-like giant bizarre cells. These megakaryocyte-like
      giant cells were positive for myeloperoxidase and CD34, but not GPIIIa and factor
      VIII, indicating that those were derived from myelogenous stem cells. Following
      the low-dose Ara-C therapy, improvement of fibrosis and disappearance of these
      giant cells were observed in the bone marrow. After the reinduction therapy with
      high-dose Ara-C and MIT against markedly increased blasts, the patient died of
      systemic fungal infection. The presence of myelofibrosis and giant atypical
      blasts might allow resistance to therapy and poor prognosis.

PMID- 8531395
TI  - [Structure and function of extracellular matrix with special references to
      proteoglycan].
AB  - To clarify the physiological significance of extracellular matrix components,
      biochemical and histochemical characterization of glycosaminoglycan and
      proteoglycan was performed. The glycosaminoglycan, chondroitin sulfate, was
      favorable to the growth of Ehrlich ascite tumor cells inoculated into the
      subcutaneous space of the mouse's back. The glycosaminoglycan content and its
      synthesis by gastric carcinoma tissue were compared with those of non-neoplastic
      mucosa, after incubation of tissue segments in medium containing 35SO4. The rate
      of glycosaminoglycan synthesis by medullary carcinoma tissue was much higher than
      that by the non-neoplastic mucosa, although no significant difference was found
      in the amount of glycosaminoglycan between them. Using human gastric carcinoma
      cell lines, the interaction of fibroblasts (cell line WI-38) with carcinoma cells
      was studied in vitro. In well-differentiated adenocarcinoma, the amount of
      glycosaminoglycan secreted into the interface between carcinoma cells and
      fibroblasts was much larger (about 20-fold) than that into the interface between
      the carcinoma cells and the bare culture dish. However, in poorly differentiated
      adenocarcinoma cells, glycosaminoglycan secretion was not affected by the
      presence of fibroblasts. The effects of the extracellular matrix produced by
      carcinoma cells on the attachment and growth of fibroblasts were also examined in
      vitro. The attachment-promoting and growth-promoting activities of the matrix
      substance produced by poorly differentiated carcinoma was about 10 times greater
      than that caused by the well-differentiated adenocarcinoma cell matrix substance.
      Proteoglycan and glycosaminoglycan were identified in malignant and benign non
      epithelial tumors. More proteoglycans containing mainly chondroitin sulfate could
      be detected in malignant tumors than in benign tumors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8531396
TI  - [Laboratory management].
AB  - Quality management in the clinical laboratory consists of quality assurance and
      good laboratory practice. A clinical laboratory as an organization is by no means
      exceptional, and good human relationship is mandatory for quality management.
      Quality management in the clinical laboratory includes 1) design control, 2) raw
      material control, 3) process control, 4) output control, 5) reliability control,
      6) verification control and 7) future strategy. Different factors influencing on
      each control step are discussed.

PMID- 8531397
TI  - [Laboratory systematization].
AB  - We have built a clinical laboratory system incorporating automatic analyzers
      (chemistry, immunology and hematology) and automatic sample dispensers. This
      laboratory system is linked with a main computer through communication lines.
      Patient's serum specimens are first treated with an automatic sample dispenser
      and then analyzed at random with automatic analyzers. Specimens which need to be
      analyzed in commercial laboratories can be dispensed with another automatic
      sample dispenser. Consequently, cost of reagents and overtime payment can be
      reduced. Security for avoiding infectious diseases is provided for laboratory
      technicians. Our clinical laboratory system can reduce the turnaround time for
      reporting diagnostic data to 30 to 40 minutes. Also, this system can reduce
      personnel expenses. However, the profits are still not satisfactory compared with
      those of commercial laboratories. Therefore, we will continue to make every
      effort to cut down the expenses for the future.

PMID- 8531398
TI  - [Cost performance and TQC in laboratory management from the aspect of a
      commercial laboratory].
AB  - Whereas per capita national income in 1992 remained in 0.3% increase, national
      fee for medical treatment showed a remarkable increase of 7.6% compared with that
      of the previous year. A recent technological innovation in laboratory medicine
      such as nonisotopic immunoassays, biosensors and DNA techniques is another factor
      to rise up the medical expense. Hospital administrator and laboratory manager
      must consider the most effective laboratory management according to complexity
      grading of tests. Nowadays, large numbers of test items are ordered from
      hospitals or clinics to reference laboratories because of cost-analysis for
      environmental security, heavy instrumentation, problem for bio-hazards and
      employee fee, etc. Since 1992, when commercial laboratories were allowed legally
      to be stationed in hospitals as called "branch laboratories", hospital
      administrators have been in consideration to introduce this system. Commercial
      laboratories, on the other hand, have come to be obliged to build a laboratory
      network from branch laboratory through regional laboratory to main reference
      laboratory with a strict responsibility of TQA including collecting specimens,
      transportation, receipt, testing and reporting results with on-line computer
      system. The most important task in the laboratory site is protection of privacy
      of patient informations, since recent systematization of laboratory tests has led
      any person working in medical record office and laboratories to easy access to
      work stations.

PMID- 8531399
TI  - [Age-related changes in amplitude ratio, duration ratio and area ratio in nerve
      conduction studies].
AB  - We investigated the effect of aging on nerve conduction parameters in 184
      subjects (aged 10-75 years) without any history or signs of peripheral
      neuropathy, in order to clarify the diagnostic parameters of demyelinating
      neuropathies in the aged. The CMAP amplitude ratio (proximal CMAP/distal CMAP),
      duration ratio and area ratio remained unchanged throughout the second to eighth
      decades. The lower limits of normal CMAP amplitude ratio (mean -3SD) were 0.79
      (median nerve), 0.74 (ulnar nerve), 0.59 (peroneal nerve), and 0.48 (tibial
      nerve). The upper limits of normal CMAP duration ratio (mean 11+ 3SD) were 1.22
      (median nerve), 1.19 (ulnar nerve), 1.35 (peroneal nerve), and 1.32 (tibial
      nerve). The lower limits of normal CMAP area ratio (mean -3SD) were 0.84 (median
      nerve), 0.78 (ulnar nerve), 0.61 (peroneal nerve), and 0.62 (tibial nerve). There
      were no age-related changes in amplitude ratio or duration ratio of SNAP,
      although the standard deviations increased with age. Since the amplitude ratio,
      duration ratio and area ratio are simple and age-independent, they can provide
      useful and reliable information for routine nerve conduction studies for aged
      patients with demyelinating neuropathies.

PMID- 8531400
TI  - [A clinicopathological study of ruptured infectious aneurysms].
AB  - We investigated 952 consecutive autopsy cases between January 1990 and May 1994
      to identify ruptured infectious aneurysms (IAs) of the aorta or iliac artery.
      Twenty patients (2.1%) died of artrial rupture, including 9 men and 11 women. The
      cause of rupture was IA in four cases (0.42%), atherosclerotic aneurysm (AA) in
      nine (0.95%), dissection (D) in six (0.63%), and aortoenteric fistula due to
      irradiation in one (0.11%). Infection of pre-existing aneurysms was considered to
      be AA rather than IA and the patient with aorto-enteric fistula was excluded from
      the study. Patients with IA were significantly older than other patients (IA:
      85.8 +/- 4.3, AA: 80.2 +/- 4.1, and D: 77.7 +/- 5.0 years old), and were less
      frequently accompanied by leukocytosis than patients with AA, although this
      difference was not significant (11,100 vs 13,000). The four patients with IA
      consisted of one man and three women, all of whom died suddenly. Two patients had
      perforation in the atherosclerotic descending aorta and the other two had
      perforation in the atherosclerotic common iliac artery. Histological examinations
      revealed marked neutrophilic infiltration in all four cases, and bacterial
      colonies in three cases. In conclusion, IAs were not rare. Since they often cause
      sudden death, special attention should be given to elderly patients who develop
      infection.

PMID- 8531401
TI  - [Clinical analysis of elderly patients with malignant lymphoma].
AB  - An epidemiological study on 173 consecutive elderly malignant lymphoma patients
      age 65 years or over was performed and the clinical outcome of chemotherapy is
      reported. Of there, 131 patients (75.7%) had non-Hodgkin's lymphoma (NHL) and 21
      patients had Hodgkin's disease (HD). As for clinical staging, 58.9% of patients
      were in stage 3 or 4. The initial sites were nodal in 61.8% of the patients the
      most common sites of involvement in superficial lymph nodes being cervical,
      inguinal and axillar. The most frequent site of extranodal involvement was the
      gastrointestinal tract. The cases were treated with CHOP/COPP, BACOP or COP-BLAM
      combination chemotherapy. The clinical efficacy of these modalities was similar,
      with complete remission rates being about 50%. However, the total response rate
      (CR+partial remission) by the COP-BLAM regimen were 88.1%. The median survival
      time of cases achieving CR, was longer than 47 months. The most frequent cause of
      death was infection, especially pneumonia and septicemia. Many elderly ML
      patients were found and diagnosed when the disease developed to an advanced
      stage. Therefore it is necessary to make efforts to find early ML patients by
      screening apparently healthy elderly people. Improvement of the complete
      remission rate should be obtained if vigorous and intensive chemotherapy is
      carried out with careful supportive therapy concerning the general condition and
      complications in patients.

PMID- 8531402
TI  - [Changes of the plasma levels of tissue plasminogen activator and plasminogen
      activator inhibitor-1 in cerebral infarction induced by the venous occlusion].
AB  - To examine the fibrinolytic system and platelet factors (PF4 and beta-TG), we
      conducted a venous occlusion test (V.O. test) on two groups of elderly patients
      suffering from cerebral infarction, one group being able to walk (A group), the
      other being bed-ridden for during a long period (B group). Their levels of t-PA,
      PAI-1 antigen and platelet factors were compared between A or B, A + B and
      healthy elderly groups. The t-PA antigen level of both group A and B after the
      V.O. test tended to increase. The t-PA values of A + B groups after the V.O. test
      were also similar to that of the healthy elderly. The PAI-1 antigen level of both
      group A and B before the V.O. test was higher than that of the healthy elderly.
      However, the PAI-1 antigen level of both group A and B tended to decrease after
      the V.O. test. No remarkable changes were noted in PF4 and beta-TG, which have
      been thought to reflect platelet function. The above findings suggest that the
      fibrinolytic activity in A or B groups can recover through stimulation by
      exercise training and some medical treatment.

PMID- 8531403
TI  - [Awareness and feelings of elderly patients and their families concerning disease
      during terminal hospitalization--malignancy versus non-malignancy].
AB  - We conducted a questionnaire survey on the awareness and feelings of elderly
      patients and their families concerning their diseases and prognosis during
      terminal hospitalization. Sixty-five families of 177 patients who died at our
      hospital in 1992 answered questions concerning estimation of the prognosis,
      understanding of the disease, satisfaction regarding explanation of the disease,
      wish to be informed of the diagnosis, feelings during hospitalization, and
      whether the family revealed the diagnosis to the patient. Patients with
      malignancy were not informed of the true diagnosis at this time. As to estimation
      of the prognosis, patients aged 70 or older who did not expect "cure" of their
      diseases at first were significantly fewer, and those anticipating "death" just
      before dying were significantly more frequent than those under age 70. In
      patients with malignancy, those aged 70 or older foresaw "incurability" at first
      significantly more frequently than those under age 70. Patients with malignancy
      knew the diagnosis in significantly fewer cases, believed the false diagnosis
      significantly more frequently, and showed dissatisfaction with the explanation of
      the disease significantly more frequently, than those with non-malignancy.
      Proportions of the family who told the diagnosis to the patient were 11.8% in
      malignancy and 38.8% in non-malignancy with statistical significance. These data
      indicate that medical care during terminal hospitalization should be modified
      principally based on informed consent, if that is the wish of the patient.

PMID- 8531404
TI  - [The effects of upper gastrointestinal endoscopy on the circulatory system of
      elderly patients as evaluated by measuring hANP and hBNP].
AB  - Endoscopic examinations of the elderly have been increasing annually due to
      increase in the size of the elderly population, and due to the development and
      increased use of upper gastrointestinal endoscopy. The reserve potential of the
      circulatory system is frequently diminished in the elderly. Thus, a minimal load
      on the circulatory system can induce a critical status. Therefore, the effects of
      endoscopic examination on the circulation, most notably on the heart itself, was
      examined in the elderly (over 60 years old) and in younger (under 30 years old)
      individuals. Atrial and ventricular load were evaluated by measuring the
      concentration of human atrial natriuretic peptide (hANP) and human brain
      natriuretic peptide (hBNP), both before and after endoscopic examination. These
      peptides are secreted by myocardial cells in reaction to sharp increases in
      cardiac load. No significant difference was observed between the blood pressure
      of the elderly group (21 cases) and that of the young group (10 cases), either
      before or after endoscopic examination. However, the pulse rate was raised
      significantly after the examination in both groups. Furthermore, the hANP
      concentration was significantly higher after the endoscopic examination in the
      elderly group, although no notable difference in hBNP concentration was observed
      after endoscopy. In the younger group, the hANP concentration did not change
      significantly, but the hBNP concentration was notably lower after the
      examination. Increased atrial load during endoscopic examination of the elderly
      was indicated by these observations. Therefore, overall patients status must be
      correctly evaluated, with particular recognition of potential circulatory system
      damage, when endoscopic examinations are performed on the elderly.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8531405
TI  - [Cardiac function in elderly patients with dementia].
AB  - Evaluation of cardiac function is very important in elderly patients because it
      is closely related to the prognosis. Appropriate evaluation is especially
      important to treat and prevent the progression of dementia since its pathology
      differs greatly depending on type. In the present study, we evaluated the cardiac
      function of patients with senile dementia using echocardiography. Included in the
      present study were 11 patients with Binswanger-type dementia (BD), 12 with
      cerebrovascular dementia (VD) of other types, 16 with senile dementia of
      Alzheimer-type (SDAT) and 15 controls. Left ventricular function was assessed by
      Mode M based on left ventricular end-diastolic dimension (LVDd), left ventricular
      end-systolic dimension (LVDs), left ventricular dimension shortening (FS), left
      ventricular ejection fraction (EF) and cardiac output (CO). LVDd was
      significantly larger in the BD group than in the control, and LVDs was also
      significantly larger in the BD group than in the three other groups. FS was
      significantly decreased in the BD group compared to the SDAT and controls. FS was
      also significantly decreased in the VD group compared to the control. EF was
      significantly decreased in the BD group compared to the three other groups, and
      it was also significantly decreased in the VD group compared to the controls.
      There was no significant inter-group difference in SV or CO. FS and EF were found
      to be decreased in patients with cerebrovascular dementia, especially BD,
      indicating the presence of latent left ventricular hypofunction in these
      patients. This finding is important in predicting the prognosis of patients and
      conducting treatment and prevention.

PMID- 8531406
TI  - [Malignant fibrous histiocytoma of the chest wall in a nonagenarian].
AB  - We report a case of malignant fibrous histiocytoma of the chest wall observed in
      a 94-year-old woman. She noticed appetite loss and general edema a week before
      admission. The patient was diagnosed as having congestive heart failure due to
      valvular heart disease on the basis of echocardiographic findings and became
      symptom-free by treatment with vasodilators and diuretics. However, chest
      roentgenogram disclosed a extrapleural mass in the left mid-lateral chest. About
      2 months after admission, she experienced left lateral chest pain for the first
      time. The chest CT scan revealed a 5 x 5 x 2 cm mass, adjacent to the lateral
      posterior chest wall and projecting into the thoracic cavity and rib osteolysis.
      Gallium-67 citrate scintigram showed abnormal isotope accumulation in the left
      middle chest. Biopsy was not done. The therapeutic approach was mainly pain
      relief, and no tumor resection, chemotherapy, or radiotherapy was performed. The
      mass increased in size, and increasingly extended into the thoracic cavity on
      follow-up CT scans. Furthermore, marked invasion of the tumor to subcutis and
      subscapula was found. She died of cachexia and respiratory failure 34 weeks after
      admission. Histologic examination revealed malignant fibrous histiocytoma.

PMID- 8531407
TI  - [Cerebrospinal fluid tau in senile dementia of Alzheimer type].

PMID- 8531408
TI  - Mark-release-recapture experiments to estimate the efficiency of the light trap
      in collecting Japanese encephalitis vector mosquitoes.
AB  - Efficiency of the light trap in collecting females of Culex tritaeniorhynchus,
      the principal vector mosquito of Japanese encephalitis, was evaluated by mark
      release-recapture experiments. Females collected with dry ice in the field were
      marked and released in a pigsty. The recapture rate of marked females by the
      light trap was so low as around 1% or lower. Owing to this low efficiency, it is
      not likely that the light trap can be a useful tool in the control of Japanese
      encephalitis.

PMID- 8531409
TI  - Patterns of lymphokine production by Semliki Forest virus-specific T-cell
      hybridomas stimulated with different antigen-presenting cells.
AB  - The development of infection seems to be influenced by the characteristics of
      antigen-presenting cells (APC) in the infection site. Thus, we compared the
      Semliki Forest virus (SFV)-antigen-presenting capacity of spleen cells, B-cell
      lymphomas, bone marrow-derived mast cells and nonparenchymal liver cells by
      measuring the production of lymphokines in SFV-specific T-cell hybridomas. Spleen
      cells were able to provide the signals needed to stimulate the production of IL
      2, IL-4, IL-6 and IFN-gamma, while B lymphomas the signals leading to only IL-2
      production. When bone marrow-derived mast cells were used as APC, SFV-specific T
      cell hybridomas produced IL-2, IL-4 and IL-6 in the presence of soluble anti-CD3
      antibody. However, no lymphokine production was detected when the SFV antigen was
      used instead of the antibody. Nonparenchymal liver cells containing liver
      endothelial cells and Kupffer cells have an APC function stimulating the
      production of IL-2 and IL-6. These findings confirmed that the T-cell hybridomas
      can be selectively stimulated by different APC to produce different lymphokines,
      and it would influence the development of the immune-mediated inflammatory
      response.

PMID- 8531410
TI  - Effect of administering cyclophosphamide and vitamin E on the levels of tumor
      marker enzymes in rats with experimentally induced fibrosarcoma.
AB  - Cyclophosphamide, and antineoplastic drug, and vitamin E, the common antioxidant
      present in the diet, were administered in separate dosages and in combination to
      animals (rats) with fibrosarcoma, metastatic tumor of the connective tissues,
      induced. The anticancer drug (20 mg/kg body weight) and the vitamin-E (400 mg/kg
      body weight) was administered for a period of 28 days from the day of tumor
      transplantation. The individual and the combined effects of these two substances
      were investigated by checking the growth of the tumor. Tumor markers like lactate
      dehydrogenase (LDH), serum glutamate pyruvate transminase (SGPT), serum glutamate
      oxaloacetate transaminase (SGOT), acid phosphatase, and alkaline phosphatase were
      analyzed for the changes in their concentration in serum, liver, and kidney to
      assess the success of the therapy. The increased level of the enzymes in the
      fibrosarcoma-suffering rats (GPII) was reduced by cyclophosphamide treatment (GP
      III) and vitamin E administration (GP IV). Among the treated groups, the
      combination therapy (GP V) showed greater efficacy in the treatment of
      fibrosarcoma than did individual administration, as there was more reduction in
      the levels of enzymes in Group V than those in to Groups III and IV. The enzyme
      levels were brought to near the normal level.

PMID- 8531411
TI  - Human alveolar echinococcosis seroprevalence assessed by western blotting in
      Hokkaido.
AB  - To investigate the recent prevalence of human alveolar echinococcosis in
      Hokkaido, we took advantage of Western blotting analysis capable of classifying
      persons infected with Echinococcus multilocularis into two groups: the complete
      and incomplete types. From the geographic distribution, the residents with the
      complete type appeared for the first time in 1992 in the Oshima district (western
      Hokkaido). The age distribution indicated that persons with the complete type
      increased, since 1990, in the age groups younger than 30 years old.

PMID- 8531412
TI  - Synaptic plasticity: stairway to memory.
AB  - Since the idea that memory is associated with alterations in synaptic strength
      was accepted, studies on the cellular and molecular mechanisms responsible for
      the plastic changes in neurons have attracted wide interest in the scientific
      community. Recent studies on memory processes have also pointed out some unifying
      themes emerging from a wide range of nervous systems, suggesting that regardless
      of the species or brain regions, a common denominator for memory may exist. Thus,
      the present review attempted to create a hypothetical and universal synaptic
      model valid for a variety of nervous systems, ranging from molluscs to mammals.
      The cellular and molecular events leading to short- and long-term modifications
      of memory have been described in a sequential order, from the triggering signals
      to the gene expression, synthesis of new proteins and neuronal growth. These
      events are thought to represent the late phases of memory consolidation leading
      to persistent modifications in synaptic plasticity, thereby facilitating the
      permanent storage of acquired information throughout the individual's life.

PMID- 8531413
TI  - Antihypertensive effects of KW-3902, an adenosine A1-receptor antagonist, in Dahl
      salt-sensitive rats.
AB  - We determined the effects of KW-3902 (8-(noradamantan-3-yl)-1,3-
      dipropylxanthine), a novel adenosine A1-receptor antagonist, on the development
      of hypertension in Dahl salt-sensitive (Dahl-S) rats. KW-3902 (0.00017% w/w
      0.017% w/w), fed with the diet, prevented the development of hypertension at 2-6
      weeks in response to the high (8% w/w) NaCl diet. KW-3902 increased urine volume
      and sodium excretion and attenuated cardiac hypertrophy. In another series of the
      experiments employing the clearance method, KW-3902 (0.1 mg/kg, i.v.) increased
      urine volume, sodium excretion and lithium clearance in anesthetized Dahl-S rats.
      These results suggest that the antihypertensive effect of KW-3902 in Dahl-S rats
      is mediated via its natriuretic effect, the site of action being, at least
      partly, the proximal tubule. The adenosine A1-receptor antagonist may be
      effective for the treatment of salt-sensitive hypertension.

PMID- 8531414
TI  - Antithrombotic effect of TA-993, a novel 1,5-benzothiazepine derivative, in
      conscious rats.
AB  - Since reported experimental models of thrombosis are not suitable for comparison
      of several drugs by oral administration, we developed a convenient model for this
      purpose by applying direct current through an intravascular electrode. In
      conscious rats, which were implanted with anodal electrodes in the abdominal
      aorta on the day before the experiment, application of 200 microA of direct
      current induced the formation of a platelet-rich thrombus around the
      intravascular electrode. Using this model, we studied the antithrombotic effect
      of the novel antiplatelet agent TA-993, (-)-cis-3-acetoxy-5-(2
      (dimethylamino)ethyl)-2,3-dihydro-8-methyl-2-(4- methylphenyl)-1,5-benzothiazepin
      4(5H)-one maleate, and compared its effect with other antiplatelet agents. TA-993
      at doses of 30 mg/kg, p.o. or more by single administration or at doses of 10
      mg/kg or more by repeated administration dose-dependently suppressed the thrombus
      formation. Aspirin (10 mg/kg, p.o. or more), cilostazol (100 mg/kg, p.o.) and
      ticlopidine (30 mg/kg, p.o. or more) also suppressed the thrombus formation by
      single administration. These results suggest that TA-993 has a comparable
      antithrombotic effect with other antiplatelet agents, and thus it is a possible
      remedy for thrombotic and embolic diseases.

PMID- 8531415
TI  - Nitric oxide-mediated neurogenic relaxation in monkey mesenteric veins.
AB  - The purpose of this investigation was to determine if neurally induced
      vasodilatation is mediated by nitric oxide (NO) in monkey mesenteric veins.
      Helical strips of the monkey mesenteric vein were exposed to the bathing media
      for isometric tension recording, and perivascular nerves were stimulated by
      nicotine. Nicotine produced a contraction, which was potentiated by treatment
      with NG-nitro-L-arginine, a NO synthase inhibitor, the effect being reversed by L
      arginine. The nicotine-induced contraction was reversed to a relaxation by
      prazosin. The relaxation was abolished by the NO synthase inhibitor, and it was
      restored by L-arginine. D-Enantiomers were without effect. The response was not
      influenced by timolol and indomethacin, but was abolished by hexamethonium and
      oxyhemoglobin. There were perivascular nerve fibers containing NO synthase
      immunoreactivity in the monkey vein. Neurally induced venous relaxations appear
      to be mediated by NO from perivascular nerves, as seen in dog and monkey
      mesenteric arteries. It is concluded that monkey mesenteric veins are innervated
      by nitroxidergic and adrenergic nerves, which may balance the vascular tone.

PMID- 8531416
TI  - Effects of intravenous anesthetics on function and metabolism in the reperfused
      working rat heart.
AB  - We investigated the comparative effects of ketamine, flunitrazepam, diazepam and
      midazolam on function and metabolism in reperfused rat hearts. Seventy-two hearts
      were rapidly excised and perfused with buffer as a Neely's working model. Whole
      heart ischemia was induced for 15 min followed by reperfusion for 20 min. Four
      intravenous anesthetics in 2 different concentrations (10 and 50 times of
      therapeutic concentrations) were administered during reperfusion. The data were
      compared to a control group in which intravenous anesthetics were not used. At
      the end of reperfusion, myocardial metabolites were measured by liquid
      chromatography. Cardiac outputs in the both groups given lower and higher doses
      of ketamine and flunitrazepam and in the groups given the higher dose of diazepam
      and midazolam were significantly lower than that in the control group [at the end
      of reperfusion: control: 60.4; ketamine: 48.8 (lower) and 14.6 (higher);
      flunitrazepam: 50.2 (lower) and 50.6 (higher); diazepam: 62.6 (lower) and 42.5
      (higher); midazolam: 59.5 (lower) and 51.2 (higher), ml/min]. The levels of ATP
      in all higher concentration anesthetic groups were significantly lower than those
      in the control group (control: 23.7, ketamine: 17.8, flunitrazepam: 17.8,
      diazepam: 17.7, midazolam: 17.7, mumol/g). These results suggest that ketamine
      and flunitrazepam moderately depress cardiac function more than diazepam and
      midazolam when they are given during reperfusion.

PMID- 8531417
TI  - Effects of GABAergic drugs on the recovery of reflex potentials after spinal cord
      ischemia in cats.
AB  - Effects of GABAergic drugs on the recovery of reflex potentials after spinal cord
      ischemia were examined in anesthethized spinal cats. Monosynaptic reflex (MSR)
      and polysynaptic reflex (PSR) potentials, elicited by electrical stimulation of
      the tibial nerve in spinal cats, were recorded from the lumbo-sacral ventral
      root. The spinal reflex potentials were immediately depressed by occlusion of the
      thoracic aorta and the bilateral mammary arteries for 10 min. The potentials
      recovered gradually to the control level within 90 min after reperfusion.
      Pretreatment with bicuculline (0.3 mg/kg, i.v.), a GABA antagonist, or
      semicarbazide (200 mg/kg, i.v.), an inhibitor of GABA synthesis, accelerated the
      recovery of PSR potentials after the removal of the arterial occlusion. In
      contrast, pretreatment with aminooxyacetic acid (10 mg/kg, i.v.), an inhibitor of
      GABA degradation, retarded the recovery of PSR potentials, and this effect was
      overcome by the addition of the opioid antagonist naloxone (10 mg/kg, i.v.).
      These results suggest that the GABAergic system retards the recovery of PSR
      potentials after a brief spinal cord ischemia, which can be antagonized by
      naloxone.

PMID- 8531419
TI  - CCKB-receptor activation augments the long-term potentiation in guinea pig
      hippocampal slices.
AB  - Effects of cholecystokinin octapeptide (CCK-8) on long-term potentiation (LTP) of
      CA1 synaptic transmission induced by tetanic stimulation of the input fibers were
      examined in guinea pig hippocampal slices. CCK-8 and a selective agonist for the
      CCKB receptor, non-sulfated CCK-8, dose-dependently augmented the magnitude of
      LTP. Concomitant application of a selective antagonist for the CCKB-receptor
      subtype, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-
      benzodiazepine-3-yl)-N'-(3-methylphenyl)urea), completely blocked the
      augmentation of LTP induced by CCK-8, whereas a selective CCKA-receptor
      antagonist, L-364,718 (3S(-)-N-(2,3-dihydro-1-methyl-2- oxo-5-phenyl-1H-1,4
      benzodiazepine)), had little effect. Thus, enhancement of LTP by CCK appears to
      be mediated by CCKB receptors. Furthermore, CCK-8 enhanced paired-pulse
      facilitation at a concentration of 10(-7) M without affecting the amplitude of
      the population spike induced by single stimulation. This effect was mimicked by a
      low dose of tetraethylammonium (TEA), a K+ channel blocker. Moreover, both CCK-8
      and TEA reduced the late component of evoked field potentials. This late evoked
      potential was diminished by increasing the extracellular K+ concentration. It is
      suggested that CCK-8 reduces the K+ conductance in CA1 pyramidal neurons. This
      reduction in the K+ conductance might be related to enhancement of the LTP.

PMID- 8531418
TI  - Changes of hepatic microsomal oxidative drug metabolizing enzymes in chronic
      renal failure (CRF) rats by partial nephrectomy.
AB  - Male SD rats, 7-weeks-old, were used to investigate the changes in the hepatic
      drug metabolizing system of chronic renal failure (CRF) model rats. Partial
      nephrectomy (5/6) was performed in a two-stage surgical procedure. After
      nephrectomy, the rats were housed under regular conditions at least 21 days.
      After confirming the CRF states, trimethadione (TMO, 100 mg/kg, i.p.) was
      administered for evaluation of the hepatic drug metabolizing capacity; the ratio
      of dimethadione (DMO: the only metabolite of TMO) to TMO (DMO/TMO) in the serum
      and the dialysate from the blood microdialysis method were ascertained. The
      hepatic drug metabolizing enzyme contents and activities were also determined. In
      the CRF rats, the DMO/TMO ratios decreased significantly; total cytochrome P450
      (CYP) contents, aminopyrine N-demethylase activity and delta-aminolevulinic acid
      synthetase activity also decreased significantly in the CRF rats. The extent of
      the alterations of these enzyme contents and activities correlated well with the
      severity of the CRF states evaluated by the serum blood urea nitrogen and
      creatinine concentrations. With Western blot analysis, the levels of CYP2C6,
      CYP2C11 and CYP3A2 decreased considerably in the CRF rats. These results suggest
      that CRF states induce not only a reduction of renal function but also an
      alteration of hepatic metabolism.

PMID- 8531420
TI  - Inhibitory effect of epinastine on superoxide generation by rat neutrophils.
AB  - We studied the effects of antiallergic drugs, epinastine, ketotifen, oxatomide,
      mequitazine and cromolyn sodium on superoxide anion (O2-) generation from rat
      neutrophils. Epinastine, ketotifen, oxatomide and mequitazine dose-dependently
      prevented the N-formyl-Met-Leu-Phe- and phorbol 12-myristate 13-acetate-induced
      O2- generation, but cromolyn sodium did not prevent it. When membrane and cytosol
      fractions were incubated with each drug, epinastine, ketotifen and mequitazine
      prevented O2- generation. On the other hand, when only the membrane fraction was
      incubated with each drug, ketotifen and mequitazine prevented O2- generation, but
      epinastine did not. Epinastine may inhibit the NADPH oxidase system through the
      obstruction of NADPH oxidase-associated cytosol components.

PMID- 8531421
TI  - [Initial clinical studies of the preparation Immucyst for immunotherapy in
      patients with carcinoma in situ (CIS) of the bladder].
AB  - Over a 12-month period, thirteen patients, 10 men and 3 women, with recurrent
      surface transitional cell carcinomas of the urinary bladder in conjunction with
      CIS, are picked out and subjected to treatment. Distribution of the patients:
      primary multiple carcinomas combined with CIS, Ta-T1/G1-G2-4 cases; recurrent
      multiple carcinomas, with CIS, Ta-T1/G2-two, recurrent multiple carcinomas,
      combined with CIS, Ta-T1/G2-five, and T1/G3-two cases. In all instances
      transurethral resection (TUR) of both visible carcinomas, and CIS areas, is
      performed. Induction Immucyst therapy is carried out according to protocol: 3
      vials BCG vaccine, dissolved in 50 ml serum, inserted intravesically once weekly
      over 6 weeks. The fluid is retained by the patients for up to 2 hours. Therapy is
      commenced within 7-14 days after TUR. Cystoscopy, cytology and biopsy of
      suspected areas ar done at 3, 6 and 12 days. Six of the patients reported on
      undergo 12-month follow-up study. The remainder (6 cases) are followed up for
      periods ranging from 3 to 6 months. At the actual stage of study, twelve patients
      are free of recurrences, and present negative cytological findings. One patient
      alone with carcinoma stage T1/G3 develops recurrence, treated with TUR and laser
      coagulation followed by immunotherapy. Two thirds of the patients sustain
      transitory pollakiuria and dysuria, and one third-subfebrile temperature
      persisting for 48 hours.

PMID- 8531423
TI  - [Pregnancy and labor under new urodynamic conditions].

PMID- 8531422
TI  - [An analysis of the surgical treatment of tumors of the upper urinary tract].
AB  - Over a ten-year period (1982-1993), forty-three patients with tumors of the upper
      urinary tract are operated in the urological clinic of the Medical University-
      Pleven. The types of operative interventions used include: radical
      nephroureterectomy with resection of the urinary bladder in 23 patients, with a
      postoperative incidence of recurrences amounting to 21.7 per cent;
      nephroureterectomy (7 cases) with 42.85 per cent recurrences; nephroureterectomy
      plus postoperative endoscopic electrocoagulation of the ureteral residue (9
      cases) with 11.85 per cent recurrences; resection of the distal portion of the
      ureter plus ureterocystoneoanastomosis (4 cases) with 25 per cent recurrences.
      Analysis of the incidence rate of recurrences after various types of operations
      shows that nonradical procedures carry greater risk. Patients where for various
      reasons radical operation is impracticable, postoperative endoscopic
      electrocoagulation of the ureteral residue and bladder mucosa surrounding its
      orifice, substantially decrease the incidence rate of recurrences.

PMID- 8531425
TI  - [Urethral strictures following transurethral resection of the prostate].
AB  - A series of 147 patients subjected to transurethral prostate resection (TUPR) are
      followed up for seven years with a special reference to urethral strictures
      development. The patients' age varies from 52 to 78 years, with an 18-month
      average postoperative observation term. The methods of diagnosis used comprise
      uroflowmetry, retrograde urethrography and urethrocystoscopy. Obstruction of the
      lower urinary ways and urethral strictures are documented in 16 cases (10 per
      cent). Usually, post-TUPR strictures occur within one to three months after the
      operation. A brief literature survey on the incidence rate of this complication,
      reported by other authors, along with a comparative assessment of the results, is
      done. The likely underlying causes involved, and the prophylactic measures
      against the complication are discussed.

PMID- 8531424
TI  - [Drainage (prosthesis) of the pyelocaliceal system].
AB  - Of 372 patients, treated in the Clinical Center of Urology-Sofia, and sixteen
      patients treated in the urological clinic at the Military Medical Academy-Sofia,
      in 241 cases various types of polyethylene drainage systems and prostheses are
      used, classified into two basic groups: intraoperative prosthetic replacement,
      and therapeutic prosthetic replacement. Intraoperative prosthetic replacement of
      the pyelocaliceal system reduces intrarenal pressure, promotes uneventful
      operative wound healing, precludes obstruction due to the so-called sterile edema
      at the site of operation, and serves as a drainage and splint; nephrostoma is
      indicated in selected cases against the background of additional complications,
      whereas prosthetic replacement during endourologic manipulations is mandatory.
      The complications associated with prosthetic replacement of the pyelocaliceal
      system are rare, and lend themselves readily to nonoperative treatment, but in
      isolated cases surgical intervention is necessitated.

PMID- 8531426
TI  - [The indications and choice for open surgical intervention in hydronephrotic
      transformation].
AB  - Out of the total of 372 patients treated for congenital and acquired
      hydronephrotic transformations over a three-year period (1990 through 1992),
      seventeen cases are subjected to treatment with antibiotics and antispasmodics
      followed by observation, and in 124 cases various types of open pyeloplastic
      procedures are performed. The indications for operative management of
      hydronephrotic transformation depends on the results of objective and laboratory
      studies, and subjective complaints. Accidentally discovered hydronephrotic
      transformations, I-II degree, may be subjected to conservative management
      followed by an observation period with good results. Of the 17 patients
      deterioration occurs in three cases, and in one of the latter nephrectomy is
      necessitated. In case of markedly expressed hydronephrotic transformation,
      associated with additional complications and renal function impairment, operation
      aimed at restoration of the patency of urinary tracts should be undertaken.
      Various types of pyeloplastic reconstructive interventions are performed, with
      the procedure suggested by Anderson-Hynnes, Foley and Davis being mainly used. In
      two patients secondary nephrectomy is done with a 96.8 per cent rate of
      successful outcomes.

PMID- 8531427
TI  - [Transurethral incision in primary bladder neck obstruction].
AB  - Sixty-one patients presenting primary obstruction of the neck of the urinary
      bladder are subjected to transurethral operative intervention and postoperative
      follow-up study in the period 1986 through 1990. The indications for performing
      transurethral incision of the bladder neck are established on the basis of
      subjective complaints against the background of data from uroflowmetry, miction
      cystourethrography and endoscopic study of the lower urinary ways. The obtained
      results point to an improvement of the subjective complaints in 74 per cent of
      the cases. In 78 per cent of the patients peak urinary flow exceeds 15 ml/sec.
      Repeated transurethral incision is necessitated in 8.1 per cent, and
      transurethral resection in the postoperative period is done in twelve patients
      (19.6 per cent). Postoperative strictures of the urethra are discovered in 8
      patients (13.1 per cent), and retrograde ejaculation is documented in three
      patients (8.5 per cent) over the maximum observation term of 64 months.
      Postoperative hospitalization is average 3.2 days (range 2.7 to 5.9 days).

PMID- 8531428
TI  - [The causes of urodynamic disorders of the urinary tract leading to
      hydronephrotic transformation].
AB  - Experience had with the treatment of 372 patients, admitted to the Clinical
      Center of Urology--Sofia, and 16 patients--to the Clinic of Urology of the
      Military Medical Academy, over the period 1990 through 1992, shows that the
      causes leading to hydronephrotic transformation comprise diseases of congenital
      and acquired nature involving upper and lower urinary tracts. Congenital
      disorders affect men and women at an equal male-to-female ratio--1:1, while
      acquired ones--at 1.8:1 male-to-female ratio; causes located in both upper and
      lower urinary tract are recorded at a 6.6:1 ratio. Proceeding from the analysis
      of the case material it is established that hydronephrosis is not a nosological
      entity of its own, but rather a symptom (complication) of a lesion (obstruction)
      located in the urinary tract. The compensatory mechanisms aimed at normalization
      of the elevated pressure affect in a varying degree the upper urinary ways, above
      the level of obstruction.

PMID- 8531429
TI  - [The morphological characteristics of the circulating blood after massive
      reinfusion in operative surgery].
AB  - Intraoperative autologous blood extravasation represents an adequate biogenic
      medium for prompt and complete blood volume compensation following acute
      hemorrhage. The efficiency of the procedure is closely related to the functional
      characteristics of the ATS applied and its potential adaptation to the operative
      field. Over a 5-year period, autologous blood reinfusion is done in 151 patients
      with acute intraoperative hemorrhage associated with various types of operative
      interventions. The hemogram is analyzed in 32 cases undergoing reconstructive
      surgery of arterial vessels, with massive intraoperative hemorrhage and
      reinfusion (exceeding 25 per cent of the circulating volume). The quantity of AB
      represents 92.7 per cent of the blood loss volume; reinfusion is effected using
      the patient's own ATS. The circulating erythron level (its binding portion)
      remains within reference limits throughout the full post-reinfusion period; a
      tendency towards complete correlative dependence between the values of Hb, Er, Ht
      and the volume of reinfusion done intraoperatively is outlined (r = 0.84-0.92; p
      < 0.05-0.001). Free hemoglobin concentration in the transfusion product is low
      (66.8 +/- 24.2 mg/100 ml blood), while in the post-reinfusion circulating blood
      it quickly returns to normal, at 2 hours--in 87.5 per cent of the samples, and at
      6 hours--in 100 per cent (r = 0.66-0.80; p > 0.001). The minimal morphologic
      changes in AB upon its deposition and reinfusion warrant the assumption that it
      is the most suitable transfusion medium, contributing to normalization of the
      hematologic indicators of acute hemorrhage during operative surgery.

PMID- 8531430
TI  - [The current principles of the conservative treatment of patients with benign
      prostatic hypertrophy].
AB  - The etiopathogenesis, risk factors, and natural history of benign prostate
      hyperplasia are issues still not well enough clarified. Hormonal factors,
      stroma/epithelial interactions and cell mechanisms are among the underlying
      causes implicated. So far, no sound criteria for the choice of a conservative
      therapeutic approach to the condition have been worked out. The diverse treatment
      alternatives include hyperthermia, balloon dilatation, and administration of 5
      alpha-reductase and aromatic inhibitors, as well as some phyto-preparations.
      Comparative assessment of the various methods point to the superiority of
      Finasterid administration. The latter, given at 5 mg daily dose leads to a
      reduction of clinical symptomatology, and decrease in prostate adenoma volume.
      The advantages of the method consist in preservation of the patient's libido and
      erectile capabilities, attributable to the normal plasma testosterone levels
      during prolonged drug taking. Specification of the indications for Finasterid
      treatment contribute to reduce operative activity in stage I of the disease.

PMID- 8531431
TI  - [A case of Fournier's gangrene with a fulminant course and fatal outcome].

PMID- 8531432
TI  - [The surgical correction of postoperative urinary incontinence].

PMID- 8531433
TI  - [A report of an intrathoracic case of hibernoma].
AB  - A successfully operated female patient, presenting hibernoma with intrathoracic
      location, is described. As shown by comprehensive survey of the pertinent
      literature, it is a matter of an exclusively rare condition--there are barely
      seven case reports worldwide on this particular type of tumor with such
      localization. The unusual clinical picture is revealed through retrospective
      analysis of the symptoms observed. Pitfalls and errors in the preoperative
      interpretation with a special reference to the massive process location are
      discussed. The results of diagnostic examinations, operative treatment and
      accurate histologic verification are documented by appropriate x-ray,
      scanographic and electron microscopic findings.

PMID- 8531434
TI  - [An orthotopic bladder from the ileum after total cystectomy].

PMID- 8531435
TI  - [The retroperitoneal transverse interureteral anastomosis--25 years later].

PMID- 8531436
TI  - [Differentiated thyroid cancer--a study of the pathomorphological variants in 216
      patients].
AB  - Two-hundred sixteen patients presenting differentiated carcinoma of the thyroid
      gland are subjected to operative treatment over the period 1980 through 1993. The
      distribution of cases by histological type is as follows: papillary carcinoma-
      127 cases, follicular--58, and mixed type (papillary-follicular)--thirty one. In
      the group presenting papillary lesions, infiltration of the capsula is noted in
      nine cases, multifocal location--in five, and microcarcinoma--in twenty three. In
      the follicular carcinoma group a markedly expressed vascular invasion is
      established in four cases, multifocal location--three, and microcarcinoma--five.
      Assessment of the morphological patterns of differentiated thyroid carcinoma
      reveals a marked predomination of noncomplicated histologic variants, enabling
      the wide use of minor conservative operative procedures, compared to
      thyroidectomy, with a positive outcome. Over he past few decades, the incidence
      of differentiated forms of thyroid gland carcinoma shows an increase, and
      nowadays it caries in the range 60 to 90 per cent. Papillary forms are
      prevailing, while follicular carcinomas are detected in 8 to 20 per cent of
      cases. An overall shift of morbidity towards younger ages and female gender is
      observed.

PMID- 8531437
TI  - [Hypophyseal-thyroid function following partial thyroid resections for euthyroid
      struma nodosa].
AB  - The serum levels of svT3, svT4, TTH, T3 and T4 are evaluated at two, six and
      twelve months after partial resection of the thyroid gland in patients with
      euthyroid struma nodosa. The patients are divided up in two groups: group one-
      given hormonal substitution therapy, and group two--untreated. The results are
      estimated with a special reference to the need of hormonal administration in view
      of precluding recurrences.

PMID- 8531438
TI  - [The incidence and morphological aspects of thyroid cancer].
AB  - A total of 10,736 biopsy specimens presenting diverse thyroid gland pathology are
      studied over the period 1974 to December 1993. The histopathological
      investigation shows that 5.45 per cent of them (n = 585) are with carcinoma.
      Comparative analysis of the incidence of thyroid carcinoma in the series
      reviewed, covering the two decades, points to a tendency of the incidence rate to
      augment from 4.03 per cent in the first decade to average 6.63 per cent in the
      second decade of study, with a frequency peak reached in the period 1986-1993.
      There is a clearcut tendency of the incidence of malignant conditions of the
      thyroid to rise among younger age groups. A markedly expressed tendency of the
      number of patients with papillary carcinoma of the thyroid, affecting mainly
      women and younger persons, to increase is also documented.

PMID- 8531440
TI  - [Early thymectomy in the treatment of myasthenia gravis].
AB  - Over a 10-year period, 1983 through 1992, in the clinic of endocrinologic surgery
      -Alexander Hospital, Sofia, 89 patients with myasthenia gravis (MG), 57 women and
      32 men, are subjected to operative treatment--thymectomy. The mean age in women
      is 32 years (range 19 to 68), and in men--45.6 years (range 25 to 70). Two age
      related distributions in the series are impressive--in female patients the peak
      is between 20 and 30 years, whereas in men--between 45 and 55 years. The
      operative intervention consists in total thymectomy. Preference is given to the
      trans-sternal median access to the thymus gland. In the complex therapeutic
      approach to MG are included also a number of drugs and other agents-
      corticosteroids, anticholinesterase agents, immunosuppressives and the like.
      Patients undergoing operative thymectomy are usually given preoperative treatment
      with anticholinesterase drugs for different periods of time. Operation is
      undertaken only in stable condition of the patients. Good postoperative results
      are recorded in 57 per cent of those operated by the first year, with a
      satisfactory improvement in 29.2 per cent of them. In the third group (13.4 per
      cent) the postoperative results are poor, and treatment is proceeded with
      anticholinesterase drugs or immunosuppressives. The average follow-up term is
      44.7 months. The delay in improvement is typical of patients with longer duration
      of the complaints, but it may be attained within 2, 3 or 5 years
      postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531439
TI  - [The routine immunohistochemical diagnosis and surgical treatment of medullary
      carcinoma of the thyroid].
AB  - Over the period 1977 through 1988, in the Research Institute of Surgery--Medical
      Academy a total of 372 patients undergo primary operative management for thyroid
      gland carcinoma. Medullary carcinoma is discovered in 18 patients of the series
      (4.8 per cent). The preoperative diagnosis is supplemented by thyroscintigraphy
      with 131iodine or technetium Tc 201. After 1981, calcitonin and carcinoembryonic
      antigen (CEA), specific medullary thyroid carcinoma (MTC) markers, measurements
      are routinely done, with substantially elevated levels in the patients under
      study being found, in those with metastases inclusive. Presumably, the
      preoperative diagnosis medullary thyroid carcinoma is very difficult, and only a
      combined approach, including thyroidectomy with ensuing iodine radiotherapy, may
      account for a good survivorship. Postoperatively, all patients with MTC diagnosis
      are regularly tested for serum calcitonin and CEA levels. The carefully taken
      family history and questioning of the patients allows to differentiate familial
      from cases from sporadic neoplasms.

PMID- 8531441
TI  - [The surgical treatment of myasthenia gravis--the authors' own experience].
AB  - Proceeding from personal experience accumulated hitherto, the indications for
      both operative treatment of MG, and choice of the most adequate preoperative
      preparation and timing of thymectomy, are precisely determined. Pathohistologic
      findings and postoperative results in 47 patients, thymectomized in the period
      1989 to 1994, are followed up and analyzed. The inference is reached that
      preliminary stabilization of the patient's condition with anticholinesterase
      drugs, and early and total thymectomy are essential for the successful outcome of
      treatment. It is preferable that thymectomy is done within six months of the
      occurrence of complaints or making the diagnosis.

PMID- 8531442
TI  - [The surgical treatment of creeping infections along the flexor tendons of the
      foot in diabetics].
AB  - Creeping infections along the flexor tendons of the foot are taken to be a common
      underlying cause of limb amputation in diabetics. Usually the process originates
      from the toes, and spreads along the course of the long flexors. The procedure of
      selective resection of the tendons involved suggested enables to complete the
      surgical treatment with economical operative intervention--amputation of a single
      toe, or amputation at transmetatarsal level.

PMID- 8531443
TI  - [Economic surgical interventions on the foot in diabetic gangrene].
AB  - Primary surgical toilet is the main stage of surgical management of diabetic
      gangrene, usually associated with amputation of isolated toes, or varying in type
      transmetatarsal amputations. Elimination of the basic tissue decomposition and
      wide exposure of all purulent cavities contribute greatly to restrict the
      purulent gangrenous process in course. Simultaneously, adequate insulin and
      antibiotic therapy is conducted. If necessary, at a second stage plastic
      reconstructive operations are performed with a view to improve the biomechanics
      of the foot.

PMID- 8531444
TI  - [The laparoscopic picture of endometriosis in women with sterility].
AB  - It is the purpose of this study to document the variegated appearance of
      endometriosis at laparoscopy, and select suitable cases indicated for
      microsurgery. Three-hundred and four patients undergo diagnostic laparoscopy
      between January 1991 and June 1992. Endometriosis diagnosed during laparoscopy is
      staged according to the classification of the American Fertility Society.
      Findings are established as follows: endometriosis--203 patients (66.77 per
      cent), adhesions without endometriosis--57 (18.75 per cent), Fitz-Hugh-Curtis
      syndrome--23 (7.56 per cent), leiomyomata--10 (3.28 per cent), ectopic pregnancy-
      3 (0.98 per cent). In eight women (2.63 per cent) there no peritoneal changes.
      Peritoneal endometriosis is characterized by the following morphological
      patterns: peritoneal pockets--38 patients (18.62 per cent), clear vesicles--26
      (12.74 per cent), scarred white lesions--24 (11.76 per cent), raised red lesions-
      21 (10.29 per cent), flat red lesions--21 (10.29 per cent), black-purple lesions-
      20 (9.3 per cent), polypoid red lesions--10 (4.9 per cent), scarred black lesions
      -6 (2.44 per cent), and yellow-brown patches--4 (1.96 per cent).

PMID- 8531445
TI  - [Thyroid cancer--its prevalence, carcinogenic factors, classifications of the
      cancer, types, variants amd prognostic factors].

PMID- 8531446
TI  - [Thyroid cancer, its diagnosis and surgical treatment].

PMID- 8531447
TI  - [Clear-cell sarcoma of the tendons and aponeuroses].

PMID- 8531448
TI  - [Struma nodosa and cancer of the thyroid].
AB  - The disputable issue of the pathogenetic relation between struma nodosa and
      thyroid gland carcinoma is discussed. A total of 234 patients with definitive
      diagnosis thyroid carcinoma, operated in the clinic of endocrine surgery--Higher
      Medical Institute, Sofia, are retrospectively analyzed. Clinical, past history
      and pathomorphologic data are considered--123 patients present papillary
      carcinoma, 67--follicular, and 42--mixed form. All patients undergo operative
      management over the period 1980 through 1991. Later, to the aforementioned group
      are added further 50 patients with carcinoma of the thyroid, treated from 1991 to
      late December 1992, and thus the total number amounts to 284 cases--153
      papillary, 79 follicular and 52 mixed forms, respectively. In 67.2 per cent of
      the cases the thyroid carcinoma presents clinical patterns of a solitary node, in
      27.8 per cent--node of multinodular struma, and in 4.9 per cent--formation
      associated with another thyroid disease. Multifocal location is established in
      five cases. As shown by the pathomorphological study in 18 per cent of the cases
      it is a matter of a combination--thyroid carcinoma and struma multinodosa, and in
      1.2 per cent of the cases only there is conclusive evidence of solitary adenoma
      malignization. The obtained results lead to the inference that thyroid carcinoma
      deriving from the nodose structures of the gland is an exception, rather than
      rule.

PMID- 8531449
TI  - [Recurrences and metastases in differentiated thyroid cancer].
AB  - A total of 201 patients presenting differentiated thyroid gland carcinoma (DTGC),
      all of them in T1-3Ha-bMo stage, are followed up over a 10-year period, 1980
      through 1989. Thyroidectomy with ensuing 131I radiotherapy is used in the
      treatment of 74 cases, and varying in extent resections--in the remainder. Women
      up to 50, and men up to 40 years of age (totalling 138 cases) are assigned to low
      risk age groups (LRG), and those exceeding the aforementioned age limit (63
      cases)--to high-risk age groups (HRG). Local recurrences and lymph node
      metastases are recorded in 17.5 per cent of the patients undergoing thyroidectomy
      followed by iodine radiotherapy. Among those subjected to radical resections the
      rate of recurrences of the lesion amounts to 2.4 per cent. In the HRG the rate of
      recurrences among thyroidectomized patients is 32 per cent, whereas in those
      assigned to LRG, treated with organ salvaging operations, the recurrences are
      10.1 and 1.1 per cent, respectively. It is established that insofar as
      recurrences of the lesion are concerned the fifth year remains a high-risk
      period; by the second year they are increased more than three times. Lymph-node
      metastases are observed in 80 per cent of the cases by the second year. Local
      recurrences are more common in HRG--83.3 per cent. As shown by the results of the
      series reviewed, thyroidectomy followed by 131I radiotherapy fails to improve the
      prognosis in HRG patients. In these cases better results are attained in those
      subjected to wide resection of the thyroid gland.

PMID- 8531450
TI  - [Fluorometric estimation of corneal endothelium functions in emmetropic and
      myopic eyes in pseudophakia].
AB  - The aim of the study was to calculate the corneal endothelial permeability (Pac)
      before, one week, and one month after planned extracapsular cataract extraction
      and intraocular posterior chamber lens implantation in two groups with axial
      myopes (8 eyes) and normal eyes (6 eyes): in patients aged 60-75 years. Patients
      with minimal endothelial disorders have been found to have abnormal endothelial
      permeabilities. Each operated eye was submitted to fluorophotometry of the
      anterior segment with measurement of corneal endothelial permeability (Fluorotron
      Master, Coherent), the day before surgery, 1 week and 1 month afterwards. The
      measuring of cornea thickness measurement and endothelial cell counting was done
      by specular microscopy with pachymeter. Corneal permeability clearly increased 1
      week after surgery in both groups; 1 months after surgery Pac was normalized in
      both groups, except for all pseudophakic myopic eyes (axial length: 25-27 mm)
      with longer surgical procedures (> 20 min), those associated with a greater
      increase in corneal endothelial permeability. No changes in corneal thickness and
      endothelial cell density were noted as a result of surgery. Myopic eye with
      longer surgical procedures was found as a risk factor for an increase in corneal
      endothelial permeability.

PMID- 8531451
TI  - [Corneal endothelium in patients with diabetes after extracapsular cataract
      extraction with intraocular lens implantation in the posterior chamber].
AB  - We have examined endothelial cell density before and 3, 6, 12 months after
      extracapsular cataract extraction with intraocular lens implantation (posterior
      chamber) in diabetic patients and in non-diabetics. We have not found
      statistically significant differences between the mean loss of endothelial cells
      due to surgery in diabetic and non-diabetic patients.

PMID- 8531452
TI  - [Implantation of bifocal intraocular lens from personal material].
AB  - Results of 25 bifocal IOLs implantations are presented. Follow-up time ranged
      from 3 to 6 months. Visual acuity for distant and near vision was estimated. The
      results were compared with a control group of 50 monofocal IOLs implantations. It
      was found that bifocal IOLs implantations enable good visual acuity for distant
      and near vision without additional correction, though visual acuity for distant
      vision was better in the monofocal group. Patients with bifocal IOLs have
      complained of glare and/or monocular diplopia more often than patients with
      monofocal IOLs.

PMID- 8531453
TI  - [Secondary intraocular lens implantation in aphakic eyes].
AB  - PURPOSE: Presentation of the results of secondary IOLs implantations in 35
      aphakic patients operated on from January 1989 to June 1994 (in the years 1989
      1994, first half). MATERIAL AND METHODS: Of 20 men and 15 women, in 17 patients
      cataract was removed by phacotomy, in 18-by intracapsular cryoextraction.
      Secondary anterior IOL implantation was performed 1 month--20 years after
      cataract surgery. The power of the lenses ranged from +17.0D to +23.5D and was
      calculated basing on the measurement of eyeball length and corneal refraction.
      RESULTS: Early complications found in 9 patients after surgery included: shallow
      anterior chamber in 2, anterior chamber haemorrhage in 1, iris "bombee" in 1,
      iritis in 1, united suteres in 2, corneal erosion in 1 and choroidal detachment
      in 1 eye. These symptoms declined one week after conservative treatment. In 2
      patients, additional corneal suteres were inserted. One month after surgery, in
      all patients, visual acuity was 5/10-5/5. In 5 eyes, slight decentralisation of
      the pupil was observed.

PMID- 8531454
TI  - [Condition of the posterior capsule in pseudophakia in children].
AB  - PURPOSE: Evaluation of the posterior capsule transparency in children after
      congenital cataract surgery with posterior intraocular lens implantation.
      MATERIAL AND METHODS: Examination comprised 41 eyes of 29 patients with posterior
      IOLS, aged 5-17 years (mean 10.3). In all cases, posterior capsule was unimpaired
      during surgery. RESULTS: During follow-up, (mean 27 months), 36.6% the eyes
      showed posterior capsule opacity of various degree. Neodymium YAG laser
      capsulotomy was performed in 13 cases and instrumental capsulotomy in 2. Opacity
      of the posterior capsule caused a decrease of visual acuity below 0.4. It
      improved after capsulotomy in all cases. No serious complications were observed.

PMID- 8531455
TI  - [Early and late results of laser trabeculoplasty in treatment of glaucoma in
      pseudoexfoliative syndrome].
AB  - PURPOSE: Evaluation of the effectiveness of laser trabeculoplasty in 23 eyes with
      pseudoexfoliative syndrome and glaucoma. METHODS: Visual acuity, intraocular
      pressure, outflow facility coefficient, visual field using static perimetry,
      gonioscopy and evaluation of the anterior and posterior segment of the eye.
      RESULTS: In the first day after treatment, a satisfactory result was found in 70%
      of eyes; after 6 months in 50%, and after 12 in 48% of cases. Laser
      trabeculoplasty is an effective method but the results are not long-lasting.

PMID- 8531456
TI  - [Persistent hyperplastic primary vitreous--diagnosis and differentiation].
AB  - PURPOSE: Presentation of the cases with a rare form of persistent hyperplastic
      primary vitreous. MATERIAL AND METHODS: 5 children, aged 3-14, were referred to
      the clinic with suspicion of neoplasm changes or congenital anomalies of the
      eyeball. Unilateral, pathological lesions, in the form of opaque membranes,
      partially or totally covered the optic disc, were found. In 2 cases persistent
      fragments of arteria hyaloidea were also observed. Diagnosis was mode basing on
      three mirror glass examination, ultrasonography and fluorescein angiography. In
      differential diagnosis, retinoblastoma and other entities determined in the
      literature as pseudo-retinoblastoma were taken into account. The children
      remained under clinical follow-up.

PMID- 8531457
TI  - [Contemporary methods for functional analysis of the optic nerve].
AB  - Complex methods of statistic analysis for parameters of automated perimetry and
      visual evoked potentials were presented. The examinations were performed in 14
      patients with compressive visual neuropathy, in 14 patients with optic neuritis,
      in 20 patients with demyelinative visual neuropathy and in 20 patients with optic
      nerve atrophy. Multidimensional analysis of variance (MANOVA) was performed. The
      methods proved useful for differential diagnosis of optic neuropathy.

PMID- 8531458
TI  - [The efficacy of "Ticlid" in treatment of diabetic retinopathy].
AB  - PURPOSE: The efficacy of "Ticlid" (ticlopidine) with insulin-dependent patients
      and early forms of diabetic retinopathy was evaluated. MATERIAL AND METHODS:
      Examinations were carried out with 52 patients (103 eyes), including 31 women and
      21 men, average age--39.9. With 33 patients (65 eyes), ticlopidine was applied
      twice a day in the dose of 250 mg, the rest, i.e. 19 patients (38 eyes), the
      control group, received a Rutinoscorbine tablet three times a day. Before the
      beginning of the treatment and then every three months the following parameters
      were examined: visual acuity for far and near distances, ophthalmoscopy,
      fluorescein angiography and colour photography of the fundus. With the group of
      patients who received ticlopidine, fibrinolytic activity of plasma (ECLT),
      threshold pro-aggregative concentration for ADP in rich platelet plasma and the
      factor of platelet aggregates (WAP) were determined. The follow-up time of the
      patients lasted from 16 to 36 months (average 21.5 months). RESULTS: More
      frequent although nonsignificant improvement and stabilization of far distance
      visual acuity was ascertained in the patients receiving ticlopidine. The same
      group manifested a significantly frequent (p < 0.02) improvement and
      stabilization of the changes in the fundus. A significant shortening of ECLT (p <
      0.01), a complete stopping of II phase aggregation, a significant (p < 0.01)
      increase in WAP could be observed as well. The above results indicate the
      favourable influence of ticlopidine on retina vessels in patients with the
      symptoms of diabetic retinopathy.

PMID- 8531459
TI  - [Use of 0.1% dipivefrine chloride for treatment of patients with open angle
      glaucoma].
AB  - PURPOSE: Evaluation of eye drops Dipivefrine chloride 0.1% produced by WZF
      "Polfa". MATERIAL AND METHODS: Drug influence on the level of intraocular
      pressure and outflow facility coefficient was examined, as well as general blood
      pressure and pulse in patients with open angle glaucoma. Effectiveness of the
      drug was compared with its analogue produced abroad. The drug was tested in 2
      groups of patients, 30 eyes in each. Statistic analysis of examined parametres we
      done after 2 weeks administration. RESULTS: Significant decrease of intraocular
      pressure was found after the administration of 0.1% Dipivefrine Chloride,
      especially in combined treatment with 0.5% Oftensin. No significant differences
      were found in outflow facility, and in comparison with the foreign analogue of
      the drug.

PMID- 8531460
TI  - [Bacterial flora in the conjunctival sac of patients before cataract surgery].
AB  - Retrospective analysis of 2365 cultures from conjunctival sac of patients was
      done. The most frequent bacteria included Staphylococcus epidermidis (48.7%),
      Staphylococcus aureus (11%) and Streptococcus (1%). The sensibility of the
      bacterial cultures for the most frequently applied chemotherapeutics was
      evaluated. Our results were compared with those in the literature.

PMID- 8531461
TI  - [Betadine for antisepsis of the conjunctival sac].
AB  - 12.5% solution of betadine is used for conjunctival sac antiseptics. To estimate
      effectiveness of betadine in 50 eyes, bacteriological examination was performed
      before and after local betadine application. Betadine is effective against
      Staphylococcus. Peptococcaceae were cultured after betadine application, in 3
      cases.

PMID- 8531462
TI  - [Use of soft contact lenses in the Riley-Day syndrome in a small child].
AB  - We present the observation of a boy treated in our Ophthalmological Department in
      Wroclaw from the age of 6 months up to 6 years for the serious keratitis with
      ulceration. We diagnosed Riley-Day syndrome with regard to many associated
      pathological features. The efficacy of the local treatment improved after
      application of soft contact lenses.

PMID- 8531463
TI  - [A triple procedure for corneal degeneration with cataract in primary idiopathic
      hypoparathyroidism].
AB  - A case of 21 year old woman with corneal degeneration similar to Salzmann's
      degeneration and binocular cataract is presented. A successful corneal
      transplantation combined with extracapsular cataract extraction followed by
      posterior chamber lens implantation was performed. Patient is undergoing a
      treatment in endocrinology ward. A rare idiopathic hypoparathyroidism with Fahr
      syndrome was ascertained.

PMID- 8531464
TI  - Formation of cocaisopropylene (isopropylcocaine) by human liver in vitro.
AB  - The formation of cocaisopropylene (CI), the isopropyl homologue of cocaine (COC),
      was demonstrated by the incubation of whole human liver homogenates with cocaine
      hydrochloride and isopropanol. Measurable concentrations of CI were noted within
      1 h of incubation. The reaction was completely inhibited by sodium fluoride. As a
      control on hepatic enzymatic activity, aliquots of the same homogenates were also
      incubated with COC and ethanol to yield cocaethylene (CE), which was previously
      demonstrated by this system. Peak concentrations of CI were approximately 0.1-0.2
      of those of CE.

PMID- 8531465
TI  - Female rhesus monkeys dosed with Aroclor 1254: analysis of polychlorinated
      biphenyl congeners in dam's milk and in the blood of dams and their offspring
      before, during, and after gestation.
AB  - Specific polychlorinated biphenyl (PCB) congeners were measured before, during,
      and after gestation in the blood of rhesus monkeys, as well as in their milk and
      in the blood of their infants during lactation, as part of a long-term feeding
      study to evaluate the toxicology of Aroclor 1254 on pre- and postnatal
      development of infant monkeys. During gestation a considerable shift from the
      higher to lower chlorinated biphenyls in the blood was observed in both dosed and
      nondosed animals. The contribution of penta- and hexachlorobiphenyls in the milk
      slightly increased with higher dosage. In addition, the percentages of 2,2'3,4,5'
      ,2,2',4,5,5'-, and 2,3,3',4',6-pentachlorobiphenyls were remarkably lower in the
      milk of dosed dams than in the originally ingested Aroclor 1254. PCB congener
      levels in infant blood increased during the lactation period but immediately
      decreased upon weaning. The lower chlorinated biphenyls virtually disappeared
      from infant blood after 16 weeks of nursing. Some correlations were observed
      between PCB congener levels in mother and infant and the congener ratios
      calculated.

PMID- 8531466
TI  - Potential interference of cyclobenzaprine and norcyclobenzaprine with HPLC
      measurement of amitriptyline and nortriptyline: resolution by GC-MS analysis.
AB  - Cyclobenzaprine and its major metabolite, norcyclobenzaprine, differ from
      amitriptyline and nortriptyline only by the presence of a double bond in the
      cycloheptane ring. Three patients developed sufficient levels of cyclobenzaprine
      and norcyclobenzaprine because of either rapid or long-term ingestion of
      cyclobenzaprine to cause positive interferences in both a Syva EMIT assay and a
      high-performance liquid chromatographic (HPLC) assay for identification and
      quantitation of tricyclic antidepressants in serum. Cyclobenzaprine coeluted with
      amitriptyline, and norcyclobenzaprine eluted slightly earlier than, but was
      poorly resolved from, nortriptyline in this HPLC assay. We found that
      cyclobenzaprine could be distinguished from amitriptyline and that
      norcyclobenzaprine could be distinguished from nortriptyline on the basis of gas
      chromatographic retention times upon gas chromatographic-mass spectrometric
      analyses after derivatization with trifluoroacetic anhydride. The compounds were
      also distinguishable by mass spectrometric criteria.

PMID- 8531467
TI  - Analysis of time-lapse changes of d- and l-enantiomers of racemic
      ethylamphetamine and stereoselective metabolism in rat urine by HPLC
      determination.
AB  - The analysis of time-lapse changes of d- and l-enantiomers after administration
      of racemic dl-ethylamphetamine (EAMP) to rats was performed by a high-performance
      liquid chromatograph equipped with a chiral activity column. After oral
      administration of dl-EAMP to five rats (dose, 15 mg/kg), the rat urine specimens
      were collected at four time intervals, 0-4, 4-12, 12-20, and 20-24 h. The two
      enantiomers of nonmetabolized EAMP and the two enantiomers of metabolized
      amphetamine (AMP) in urine were simultaneously detected within 20 min. The rate
      of urinary excretion during 24 h was 3.67% for d-EAMP, 1.03% for l-EAMP, 2.14%
      for d-AMP, and 1.92% for l-AMP. The total percent of the excreted doses of EAMP
      and AMP was approximately 8.8% of the administered dosage of dl-EAMP (5.81% for
      the d-enantiomers and 2.95% for the l-enantiomers). The l/d ratio was 0.51, which
      was significantly smaller than that (1.01) of the original dl-EAMP powder used (p
      < .01). The percentages of the doses of l-EAMP in each collection time were
      significantly less than those of d-EAMP (p < .01), and the l/d ratios of
      nonmetabolized EAMP decreased to 0.17 within 24 h. For the AMP metabolites, there
      was a somewhat greater percentage of l-AMP in urine collected up to 4 h than d
      AMP (p < .05). Thereafter, it decreased more slowly than d-AMP with time. The l/d
      ratios of AMP changed from 1.57 to 0.76 within 24 h. The greater decrease of l
      EAMP as compared with d-EAMP suggested the stereoselective metabolism of dl-EAMP
      in rats.

PMID- 8531468
TI  - A case of acute dapsone poisoning: toxicological data and review of the
      literature.
AB  - A case of nonfatal, acute poisoning following the ingestion of an undetermined
      amount of dapsone (DDS) in a 49-year-old woman is presented. The clinical
      features were dyspnea and deep cyanosis. Methemoglobinemia was 39.0% on
      admission. DDS was identified and quantitated in blood samples taken on the third
      day (sample A) and fifth day (sample B) in the hospital using a high-performance
      liquid chromatographic technique with diode-array detection. DDS concentrations
      were 26.99 and 8.40 micrograms/mL in samples A and B, respectively. Results are
      discussed in the light of an extensive review of the literature (1950-1993)
      available on DDS poisonings.

PMID- 8531469
TI  - Solvent optimization for the direct extraction of opiates from hair samples.
AB  - The hair samples of six opiate addicts, who died after heroin overdose, were
      investigated by gas chromatography-mass spectrometry after extraction with 10
      solvents differing in polarity and hydrophilicity in an ultrasonic bath.
      Morphine, 6-monoacetylmorphine (MAM), and codeine were detected in all cases, and
      heroin was detected in four cases. With toluene, which is hydrophobic, almost no
      extraction occurred, and with the nonprotic solvents dioxane, acetonitrile,
      acetone, and dimethyl sulfoxide, only a relatively low extraction rate was found.
      The yield increased in the series of alcohols from n-propanol to isopropanol to
      ethanol to methanol. Water proved to have almost the same extraction capability
      as methanol. Using equal conditions, the extraction rate of the opiates decreased
      in the following order: heroin > MAM > morphine approximately codeine. Addition
      of 1% acetic acid or 1% triethylamine to methanol led to a decrease in the heroin
      yield and an increase in the morphine yield. The results are discussed in terms
      of the binding between the hair matrix and the drug, the penetration of the
      solvent into the hair, and the solubility of the drug in the solvent.

PMID- 8531470
TI  - Ethanol in biological fluids: headspace GC measurement.
AB  - The present study evaluates the suitability of headspace gas chromatography (GC)
      with a capillary column as a method for determining the ethanol content in
      different biological fluids. This procedure allows the use of headspace GC not
      only as a reference method but also in routine diagnostics and monitoring work.
      The recent literature reviewed reports no standardized methodology that is at the
      same time suitable for ethanol determination in all routinely available
      biological fluids (blood, serum, plasma, urine, and saliva). The proposed
      procedure seems to be a good solution to the problem. The reproducibility study
      for the biological fluids tested resulted in coefficients of variation that
      ranged from 0.8 to 2.9% and recoveries that averaged 99%. Linearity was verified
      in the range of 0.01-20 g/L of ethanol in aqueous solutions. Sensitivity was
      determined to be 0.01 g/L. Ethanol measurement by this method is easy, simple,
      and highly reliable, and only a small sample volume (0.1 mL) is required. An
      internal standard and sample manipulation are not necessary. The obtained results
      suggest that the use of headspace GC could be extended from confirmatory analyses
      to routine application in many biomedical fields.

PMID- 8531471
TI  - Cocaethylene (ethylcocaine) detection during toxicological screening of a
      university medical center patient population.
AB  - Cocaethylene (ethylcocaine) (CE) was incorporated into this laboratory's urine
      toxicological screening protocol more than 1 year ago. During a 1-year period,
      451 urine specimens tested positive for benzoylecgonine (BE) and/or cocaine (COC)
      and/or CE using a combination of thin-layer chromatography with enzyme
      immunoassay confirmation. CE was detected in 57 urine specimens. Blood ethanol
      (EtOH) analysis was available for 37 of these cases, and the mean concentration
      (1320 mg/L) was significantly higher than that found in 117 blood EtOH assays
      performed for the CE-negative patients (630 mg/L) (p < .01). In two instances, CE
      was noted in urine in the absence of EtOH in the corresponding blood. Without
      exception, CE, when present in urine, was always detected with both BE and COC.
      Most of the time, no other drugs were found. In one instance, CE was present in
      the urine of a neonate but was not detected in that of its mother. Demographic
      and analytical findings are presented for both CE-positive and CE-negative cases.

PMID- 8531472
TI  - Toxicology of 2,4-dichlorophenoxyacetic acid (2,4-D) and its determination in
      serum and brain tissue using gas chromatography-electron-capture detection.
AB  - A gas-liquid chromatographic method with an electron-capture detector was applied
      for 2,4-dichlorophenoxyacetic acid (2,4-D) determination in the serum and brain
      tissue of rats acutely intoxicated with the dimethylamine salt of 2,4-D. After
      extraction with ethyl ether, 2,4-D derivatization was performed using 2
      chloroethanol and BCI3. The average recovery values found for serum and brain
      tissue were 98.5 +/- 4.8 and 93.3 +/- 7.5, respectively. The sensitivity limit of
      the method was 250 ng/mL for serum and 300 ng/g for brain tissue. The toxic
      effects of 2,4-D in rats were observed within one-half hour after its oral
      administration. Results suggest that the toxic mechanism of 2,4-D is related to
      an action on the central nervous system.

PMID- 8531473
TI  - Development of a biomonitoring assay for ortho-toluidine or its metabolites in
      human urine.
AB  - We describe a method for the measurement of a metabolite of ortho-toluidine in
      urine. The method uses capillary gas chromatographic separation with mass
      spectrometric detection to quantitate the metabolite, and it requires no
      derivatization or extraction of the urine sample prior to analysis. Quantitation
      is accomplished by comparison with a control spiked with a standard of the
      metabolite. The coefficient of variation for day-to-day reproducibility of the
      assay was 9.7%. The limit of quantitation was 10 micrograms/L (10 parts per
      billion).

PMID- 8531474
TI  - Application of high-performance liquid chromatography to a fatality involving
      azide.
AB  - We describe a fatality resulting from the ingestion of sodium azide. Initial
      routine toxicological screening of the blood showed a negative result, but
      pathological findings as well as findings at the scene itself led to the search
      for azide. The azide was quantitated in all available postmortem samples (blood,
      stomach contents, liver, kidney, and bile) and was present in all of these
      matrices in the following concentrations (micrograms per milliliter or micrograms
      per gram): 262, 754, 14, 205, and 1283, respectively. The method is based on
      precolumn derivatization with 3,5-dinitrobenzoyl chloride followed by isocratic
      high-performance liquid chromatography and photodiode array detection.
      Methemoglobin and cyanide content in the blood were also elevated.

PMID- 8531475
TI  - Two fatalities involving phenelzine.
AB  - Phenelzine is a drug commonly used in the treatment of depression. Fatalities due
      to phenelzine have been infrequently reported in the medical literature. The
      authors report two cases in which phenelzine levels in blood at autopsy were 10
      50 times greater than therapeutic levels. Although in both cases other drugs were
      present in elevated levels, the concentrations of phenelzine were so greatly
      elevated as to be considered as an independent cause of death.

PMID- 8531476
TI  - Cotinine content in control serums.

PMID- 8531477
TI  - Influenza vaccine may enhance theophylline toxicity. A case report and review of
      the literature.

PMID- 8531478
TI  - Pneumococcal pericarditis: a rare complication of pneumonia.

PMID- 8531479
TI  - Negligent delay or judgement call gone bad.

PMID- 8531480
TI  - Community-wide epidemic of hepatitis A--Shelby County, Tennessee.

PMID- 8531481
TI  - The pain of Christmas.

PMID- 8531482
TI  - Automation of the social interaction test by a video-tracking system: behavioural
      effects of repeated phencyclidine treatment.
AB  - The social interaction test is a valuable behavioural model for testing
      anxiolytic and neuroleptic drugs. The test quantifies the level of social
      behaviour between pairs of rats and it is usually based on manual analysis of
      behaviour. Advances in computer technology have made it possible to track the
      movements of pairs of rats in an arena, and the present paper describes the
      automation of the social interaction test by the commercial video-tracking
      programme, the EthoVision system. The ability of the automated system to
      correctly measure the social behaviour of rats is demonstrated by determining a
      dose-response relationship in the social interaction test for phencyclidine, a
      psychotomimetic drug that reduces social behaviour between pairs of rats. These
      data are subsequently analysed by the manual and automated data-acquisition
      methods and the results are compared. The study shows that the automated data
      acquisition method best describes the behavioural effects of phencyclidine in the
      social interaction test by the locomotor activity of the rats, how much time the
      rats spend in different sections of the testing arena, and the level of social
      behaviour. Correlation analysis of the results from the manual and automated data
      acquisition methods shows that the social behaviour measured by the automated
      system corresponds correctly to the social behaviour measured by the manual
      analysis. The present study has shown that the automated data-acquisition method
      can quantify locomotor activity, how rats use a testing arena and the level of
      social behaviour between rats in the social interaction test. The system cannot
      distinguish between social and aggressive behaviours, and therefore the rats
      should be tested in an unfamiliar arena to reduce territorial behaviour. Taking
      this limitation into consideration, the social interaction test can be automated
      by this computer-based video-tracking system and can be used as a routine test
      for quantifying the effects of drugs on the social behaviour of rats.

PMID- 8531483
TI  - Microdialysis as a tool for in vivo investigation of glutamate transport capacity
      in rat brain.
AB  - The role of glutamate as a possible mediator of neurodegeneration is well
      described, and the homeostasis of extracellular glutamate is considered of major
      importance when addressing the pathogenesis of excitatory neurodegeneration.
      Applying the 'indicator diffusion' method to the microdialysis technique, we
      present a method that is suitable for the in vivo investigation of the capacity
      of cellular uptake of glutamate. Using 14C-mannitol as reference, we measured the
      cellular extraction and the cell membrane permeability of the test substance 3H-D
      aspartate in the corpus striatum of the rat brain. The cellular extraction
      fraction of 3H-D-aspartate was 0.29, and the cell membrane permeability 2.24 x
      10(-4) cm/s. In the presence of the glutamate-uptake blocker DL-threo-beta
      hydroxyaspartate (THA) the extraction of 3H-D-aspartate was completely abolished,
      indicating that extraction of 3H-D-aspartate was due to cellular uptake by
      glutamate transporters. The cell membrane permeability towards 3H-D-aspartate was
      reduced by approximately 98% due to THA, indicating that the cell membranes per
      se are highly resistant to diffusion of 3H-D-aspartate. It is concluded that the
      present method can be used in studying the capacity of the glutamate transporters
      in vivo.

PMID- 8531484
TI  - Non-linear summation of responses in averages of rectified EMG.
AB  - Studies on the motor system commonly use averages of rectified electromyogram
      (EMG) to measure muscular response. The assumption is usually made that this is a
      linear measure of response magnitude. It is shown here using a theoretical and
      experimental model that averages of rectified EMG can lead to non-linearities,
      which are of particular importance when considering the summation of two
      independent responses. When responses had a highly stereotyped waveform from
      trial to trial, so that averages of unrectified EMG revealed a deflection from
      zero, in measurements from averages of rectified EMG the size of a response to
      two stimuli delivered together was greater than the linear sum of the responses
      to each stimulus delivered alone. This deviation from linearity was greatest when
      two responses which were small relative to the ongoing background EMG activity
      were combined. The total response was then as much as twice as large as the
      linear sum of the individual component responses. Conversely, under conditions
      where responses were highly variable from trial to trial, resulting in no
      consistent deflection being seen in an average of unrectified EMG, the summed
      responses in rectified and averaged EMG were smaller than expected if summation
      were linear. This effect was most pronounced when both component responses were
      relatively large; the combined response tended asymptotically to approximately
      70% of the linear sum of the component responses. A practical method is presented
      which allows prediction of the size of a response to two stimuli given together,
      when measured from averages of rectified EMG, on the assumption that they act
      independently.

PMID- 8531485
TI  - Imaging of L-type Ca2+ channels in olfactory bulb neurones using fluorescent
      dihydropyridine and a styryl dye.
AB  - We have imaged the fluorescence of dihydropyridine-Bodipy (fDHP) in cultured
      olfactory bulb neurones in order to investigate the subcellular distribution of L
      type calcium channels in these neurones. The neurones were stained with both fDHP
      and the voltage-sensitive styryl dye RH414. The fluorescence emission maxima of
      these dyes were in the green and red ranges of the spectrum, respectively, and
      were recorded by the 2 photomultiplier channels of a laser scanning microscope.
      The fDHP images were ratioed with the RH414 images taken simultaneously. The
      resulting ratio images revealed the spatial distribution of the surface density
      of L-type calcium channels. This density was highest on somata, in particular at
      the base of dendrites, and decreased with the distance from this maximum. Two
      classes of dendritic L-type channel distributions were observed: one with a
      homogeneously low density and another one with a characteristic gradient of the L
      type channel density along proximal dendrites. This subcellular localization of L
      type calcium channels is discussed in the light of specific functional roles.

PMID- 8531486
TI  - Conditions required for the measurement of nitric oxide synthase activity in a
      myenteric plexus/smooth muscle preparation from the rat ileum.
AB  - Nitric oxide synthase (NOS) activity was measured, by the conversion of arginine
      to citrulline, in a preparation from the rat ileum consisting of the myenteric
      plexus and smooth muscle layers. A variety of incubating media were used in order
      to establish the optimal conditions required for the assay. NOS activity was
      present in the soluble fraction and was Ca(2+)- and calmodulin-dependent,
      characteristic of neuronal NOS. Exogenous Ca2+ was required for activity to be
      detectable but NOS activity progressively decreased with Ca2+ concentrations
      above 1.25 mM. Activity varied with arginine concentration, reaching saturation
      at 6 microM, and required the addition of the co-substrate NADPH. Endogenous
      levels of co-factors in the crude soluble fraction were not sufficient to
      maintain NOS activity. Omission of flavin adenine dinucleotide and
      tetrahydrobiopterin from the incubation medium reduced activity by 90%, and both
      co-factors had to be present for maximal activity to occur. These results
      emphasize the need to control assay conditions when measuring NOS activity in
      crude preparations from peripheral tissue.

PMID- 8531487
TI  - Development and application of a modified monoclonal hybridoma technique for
      isolating monoclonal antibodies to human brain regions.
AB  - We developed a modified monoclonal hybridoma technique that combines two
      conventional methods: a conventional immunosuppression method with
      cyclophosphamide treatment and an in vitro immunization method. This technique is
      advantageous over conventional methodologies because it requires a shorter period
      for immunization of mice and a smaller quantity of antigen, and gives rise to
      antibody-secreting hybridomas with higher efficiency. One monoclonal hybridoma
      line, designated as BG5, was established by this technique after activation of
      lymphocytes with muramyl dipeptide and with the immunogen obtained from human
      entorhinal cortex. Western blot analysis showed a relatively high expression of
      BG5 antigen in human entorhinal cortex. Our results suggest that this modified
      hybridoma technique may rapidly facilitate the acquisition of brain region
      specific antibodies. We call this technique 'suppression immunization followed by
      in vitro stimulation procedure' (SOFISTIC).

PMID- 8531489
TI  - The effects of low-pass filtering on the primary cortical auditory potential of
      the rat.
AB  - The effects of low-pass filtering on the primary cortical auditory evoked
      potential (CAEP) were studied using the rat as subject. The CAEP is the potential
      which is generated by the arrival of the afferent volley in the primary auditory
      projection area. Recordings were made from animals which were totally awake and
      those which were anaesthetised with pentobarbital. A total of 9 recordings were
      obtained from each subject. The high-pass (low-frequency) filter remained fixed
      at 3.2 Hz while the low-pass (high-frequency) filter was set at 32, 80, 160, 320,
      800 Hz and 1.6, 3.2, 8 and 16 kHz. The CAEP recorded from the awake animal
      consisted of a primary positivity (P1) followed by a later secondary positivity
      (P2). In the anaesthetised subjects, only the P1 potential was present. As the
      bandpass was progressively opened, there was at first a quite steep decline in
      latency associated with a gradual increase in amplitude. After the low-pass
      filter setting had been raised to 320 Hz, the amplitude of components P1 and P2
      when awake and of P1 when anaesthetised had stabilized and thereafter there was
      no additional increase. Likewise, the latency of P2 for the awake subjects
      subsequently remained constant. In contrast, the latency of P1 recorded from both
      awake and anaesthetised subjects showed a continuing small decline as the
      bandpass was extended to 3.2-16 kHz. It is probable that this phenomenon did not
      represent a further genuine decrease in the latency of P1 but was more likely an
      artefact caused by the distorting effects of a cluster of late high-frequency
      components of the brainstem auditory evoked potential generated temporally
      contiguous to P1. It was concluded that a bandpass of 3.2-320 Hz is optimal for
      recording both early and late components of the CAEP and that low-pass filtering
      had an essentially uniform effect on the waveform irrespective of the subject's
      state of arousal.

PMID- 8531488
TI  - A reliable and sensitive method for non-radioactive northern blot analysis of
      nerve growth factor mRNA from brain tissues.
AB  - This report describes a sensitive, rapid and reproducible protocol for non
      isotopic Northern blotting analysis. Church buffer and probes labeled with
      digoxigenin (DIG) were used for studying the expression of nerve growth factor
      (NGF) in the rat brain. Using the described method, NGF cRNA probe was hybridized
      to blotted RNA and the results were compared to Northern blot obtained using the
      method recommended by the manufacturer (Boehringer Mannheim). Comparison revealed
      that the blot treated with Church buffer detected at least 10-fold more NGF mRNA
      as compared to blot hybridized with formamide buffer. In summary, we have
      developed an optimal hybridization protocol to perform non-radioactive Northern
      blot analysis using antisense RNA as a probe. This method allowed us to detect
      the specific low-abundant mRNA and analyze the expression of neurotrophic factors
      in the rat brain.

PMID- 8531490
TI  - A simple method for quantifying changes in neuronal populations in primary
      cultures of dissociated rat brain.
AB  - A simple method which allows easy quantification of neuronal and glial sub
      populations in primary neuronal tissue culture is described. The method takes
      advantage of the fact that the staining of neuronal and glia nuclei with Hoechst
      33258 is distinctive and characteristic of the cell type. Double-staining
      experiments show that only cells with nuclear staining characteristic of neurones
      are immunopositive for neuronal markers. There is no obvious difference between
      neurones from different regions of the brain nor any apparent differences in
      nuclear staining of neurones of different sizes. This method is particularly
      useful for the quantification of neurones in cultures where neurones are growing
      on glial beds or where the neurones are growing in clusters. Further, it
      eliminates the need to double-stain cultures with neuronal markers in order to
      calculate neuronal sub-populations. We have used this technique to examine the
      effect of time in vitro on the proportion of calbindin D28K-positive neurones in
      striatal cultures. We show that with increasing time in culture, there is a
      significant increase in the percentage of neurones which express calbindin D28K.
      This supports the suggestion that calbindin D28K may be important for promoting
      the survival of neurones in which it is expressed.

PMID- 8531491
TI  - Stimulation, data acquisition, spikes detection and time/rate analysis with a
      graphical programming system: an application to vision studies.
AB  - A Macintosh-based system performs stimulus control and data acquisition, and an
      off-line analysis, in experiments on visually driven neurons in frog. The
      stimulus is a target moved on a modified XY recorder. The computer is equipped
      with a multifunction input/output board to perform stimulus control and data
      acquisition. The graphical programming system LabVIEW 2 was used to develop the
      'Vision 93' package made of 4 main 'virtual instruments' (VIs). By means of DOCS
      Exp, the user controls the experiment via screen displays which look like front
      panels of electronic instruments. DOCS-Preproc performs a user-controlled spike
      detection and computes mean impulse rate values. DOCS-SAS displays the
      instantaneous frequency, mean impulse rate, spike counts or interspike time
      intervals as staircase histograms and/or spline smoothed curves. Finally, DOCS-x
      Functions computes and graphs quantitative stimulus/response relationships in
      terms of velocity, diameter, orientation and configuration of the target. The
      functionalities of these main VIs are presented and original software components
      are detailed. System operation is illustrated by using the successive VIs to
      process a sample signal record.

PMID- 8531492
TI  - The square-wave approach to impedance measurement of brain tissue water dynamics.
AB  - Electrical properties of living soft tissue have been used to analyze their
      structure and function. Presently, the 'admittance locus' method, with the sine
      wave signal of changing frequency, is the most informative continuous method for
      analyzing extra-and intracellular water content in brain tissue. Using the square
      wave signal in lieu of the sine-wave signal, we can avoid cumbersome and costly
      measurements and facilitate real-time data processing. An isolation-calibration
      device was developed for the present study in order to condition and stabilize
      electrical current through the brain cortex. This device was also used for
      impedance calibration before and after the experiments. We propose a simple
      algorithm for data analysis on the basis of equivalent circuit approach, which
      allows to develop a computer program for data processing. Preliminary experiments
      on rat brains were carried out with a 0.2-0.5 mm stainless-steel tetrapolar
      electrode system. These studies showed good linearity between stimulating
      currents (I = 5-30 microA) through the external electrodes in the brain cortex
      and a drop in voltage which was measured by 2 inner electrodes. The results of
      the device and the program accuracy tests allow us to choose the optimal range
      for the working current. We can recommend this method for usage in animal
      experiments.

PMID- 8531493
TI  - Comparative evaluation of acute cerebral vasospasm by the microsphere and the
      angiography techniques.
AB  - Experimental subarachnoid haemorrhage (SAH) induces an acute transient cerebral
      vasospasm. The goal of this study was to compare angiography with iterative
      measurements of regional cerebral blood flow (rCBF) by the microsphere technique
      for tracking acute cerebral vasospasm after SAH. Cerebral vasospasm was induced
      in anaesthetised rabbits by injecting 1 ml of fresh blood in the cisterna magna.
      In a first experiment, the diameter of the basilar artery was measured by
      repeated angiograms over 60 min. In a second experiment, rCBF was measured over
      60 min by the radioactive microspheres method without and with bilateral ligation
      of the carotid artery. Without carotid ligation, despite a profound transient
      vasospasm of the basilar artery, rCBF was unchanged in the cerebellum and
      cerebrum and was not statistically decreased in the brain stem. However, with
      bilateral carotid ligation, rCBF dramatically decreased at 5 and 15 min after
      haemorrhage. At 30 min, despite a persistent 50% decrease in the basilar cross
      sectional area, rCBF was no longer different from the control group. Thus in a
      model of acute vasospasm of the basilar artery, rCBF evaluation by the
      microsphere technique parallels the cerebral vasospasm evaluated by angiography
      only when both carotid arteries are ligated.

PMID- 8531494
TI  - A re-evaluation of the ultrastructural localization of 5'-nucleotidase activity
      in the developing rat cerebellum, with a cerium-based method.
AB  - The membrane ectoenzyme 5'-nucleotidase converts 5'-AMP into adenosine which, in
      the nervous tissue, plays an important role as intercellular messenger. Moreover,
      during histogenesis, 5'-nucleotidase seems to be related to cell proliferation
      and migration. Conflicting data are reported in the literature about the
      localization (neuronal or glial) of 5'-nucleotides in the rat cerebellum. In the
      present report we have analyzed the distribution of 5'-nucleotidase activity with
      electron microscopy, using a cerium-based method, at different postnatal
      histogenetic stages (postnatal days (PND) 11, 17, 28). On PND 11 and 17, rims of
      reaction product outlined the plasma membranes of some neuroblasts in the
      external granular layer and of parallel fibers and some migrating cells in the
      developing molecular layer. Positivity was frequently observed on membranes of
      adjacent neuronal cells and glial processes. Moderate activity was also present
      on the membranes of granule cells and of mossy fiber rosettes and granule cell
      dendrites constituting the cerebellar glomeruli within the internal granule cell
      layer. At PND 28, the reaction product was slightly reduced in some
      localizations. Cytochemical patterns prove that the cerium-based method is
      suitable for demonstration of 5'-nucleotidase-specific activity. In fact, a
      continuous and fine reaction product appears strictly linked to the cell
      membranes, and no unevenly scattered precipitates can be observed. Data suggest
      that, during cerebellar histogenesis, 5'-nucleotidase may be involved in the
      mechanisms of cell migration and proliferation. However, in adulthood, prominent
      localization of the reaction product on neuronal elements suggests a major role
      in neuromodulation processes for the enzyme.

PMID- 8531495
TI  - A novel quantitative receptor autoradiography and in situ hybridization
      histochemistry technique using storage phosphor screen imaging.
AB  - A new technique of image acquisition for quantitative receptor autoradiography
      and in situ hybridization histochemistry was developed using storage phosphor
      screen imaging. This method was at least 4-5 times faster than conventional film
      densitometry. Two of the advantages of the phosphor screen method are high
      sensitivity and wide linear range of response. Other aspects of this method were
      compared with those of conventional densitometry. Use of storage phosphor screen
      imaging will allow greatly increased speed of pharmacological screening
      procedures that utilize quantitative autoradiography.

PMID- 8531496
TI  - Sensitivity of valinomycin-based K(+)-selective micro-electrodes to inhibitors of
      K+ transport.
AB  - The sensitivies of double-barrelled K(+)-selective micro-electrodes (KSMs)
      employing the low-impedance membrane cocktail based on the neutral K(+)-selective
      ion carrier valinomycin (Fluka, Cocktail B 60398) to the following 3 different
      classes of inhibitors of K+ transport were measured: (1) general metabolic
      inhibitors (dinitrophenol, potassium cyanide, sodium azide, rotenone,
      dicyclohexylcarbodiimide, salicylhydroxamic acid); (2) P-type ATPase inhibitors
      (vanadate, ouabain, amiloride, SCH 28080); and (3) anion-dependent K+ transport
      inhibitors (bumetanide, 4-acetamide-4-isothiocyanostilbene-2,2-disulphonic acid).
      Of the 12 inhibitors tested, only dinitrophenol had any significant effect on the
      response of KSMs to K+ activity. Comparison of the calibrations in solutions with
      and without 0.1 mM dinitrophenol showed that this inhibitor behaved as a
      'classical' interferent whereby its contribution to the K+ activity signal was
      statistically significant at K+ activities of 36.0 mM and less. However, at
      higher K+ activities (97.0 mM), dinitrophenol interference was not significant.
      It was possible to correct for the DNP interference and to obtain measurements of
      intracellular K+ activity in insect muscles.

PMID- 8531497
TI  - Toluene diisocyanate induction of airway hyperresponsiveness at the threshold
      limit value (10 ppb) in rabbits.
AB  - Induction of acute lung injury and the development of airway hyperresponsiveness
      (AHR) by toluene diisocyanate (TDI) exposure was studied in a new rabbit model of
      occupational lung diseases. TDI in the range of the threshold limit value (TLV)
      of 10 ppb, as well as at 5 and 30 ppb, administered four times over a period of 1
      h to three groups of eight rabbits, did not significantly alter airway resistance
      (RI), dynamic elastance (Edyn), slope of inspiratory pressure generation (delta
      Pes/tI), arterial pressure (Pa) or arterial blood gas tensions (PaO2, PaCO2).
      Airway responsiveness (AR) to aerosols of 2% acetylcholine (ACH) was measured
      before and after each TDI exposure. After TDI inhalation of 10 ppb over 4 h, the
      amplitude of the ACH-induced airway constrictor response indicated by the changes
      in Edyn rose significantly to almost twice the control response value (p <
      0.005). Similar changes in the amplitude of RI and in the slope of delta Pes/tI
      were obtained. After inhalation of 5 ppb TDI, no changes in airway reactivity
      were observed. The responses of respiratory mechanical parameters to ACH rose to
      three to four times the control responses after exposure to 30 ppb TDI. In a
      control group of eight animals not undergoing TDI exposure, no significant
      changes of respiratory responses were obtained after inhalation of 0.2% ACH for 1
      min. In summary, TDI atmospheres in the range of TLV increased AR to ACH within 4
      h of exposure in this rabbit model. This augmented AR may indicate an increased
      risk for the development of isocyanate-induced obstructive lung diseases.

PMID- 8531499
TI  - Lung cyclic nucleotides in exercise-trained rats attenuate hypoxic pulmonary
      vasoconstriction.
AB  - We examined the effects of exercise training on pulmonary arterial blood pressure
      (Ppa) and on adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'
      cyclic monophosphate (GMP) concentrations in lung tissue at rest and during
      exercise under hypoxic conditions in catheter-implanted rats. Male Wistar rats
      were divided into an exercise-trained group (ET, n = 32) and nonexercised control
      group (control, n = 32). ET rats exercised 40 min/day 6 days/week for 6 weeks, at
      an altitude of 610 m on a treadmill. The mean Ppa levels of the ET were
      significantly lower than those of controls at rest and during exercise at 610-
      and 2500-m altitudes. The exercise-induced mean Ppa increase in the ET was less
      than that in controls at both 610- and 2500-m altitudes. Resting lung cAMP
      increased more in the ET than in controls at both 610- and 2500-m altitudes. In
      ET, cGMP was significantly greater at the 2500-m altitude than at the 610-m
      altitude at rest and just after exercise. Hypoxic exercise in ET was accompanied
      by a preferential increase in cGMP but not in cAMP. These results suggest that
      the intracellular augmentation of cAMP and cGMP in ET plays an important role in
      attenuating hypoxic pulmonary vasoconstriction (HPV) and exercise-induced
      increases in Ppa.

PMID- 8531498
TI  - Arachidonic acid metabolites and glucocorticoid regulatory mechanism in cultured
      porcine tracheal smooth muscle cells.
AB  - To elucidate the signal transduction system in the production of prostaglandin E2
      (PGE2) by porcine tracheal smooth muscle cells in culture (PTSMC), we examined
      the pattern of arachidonic acid metabolites released from PTSMC and the
      relationship between bradykinin-stimulated rises in intracellular calcium
      concentration ([Ca2+]i) and PGE2 production by PTSMC. We next examined the effect
      of dexamethasone on these parameters. Bradykinin induced a dose-dependent
      increase in both the rise in [Ca2+]i and PGE2 production by PTSMC. The increase
      in [Ca2+]i paralleled an increase in PGE2 production. High-performance liquid
      chromatography (HPLC) revealed that dexamethasone-treated PTSMC were suppressed
      to release arachidonic acid metabolites such as PGE2 and prostaglandin F2 alpha
      (PGF2 alpha). Incubation of PTSMC with 10(-6)M dexamethasone for 24 h
      significantly suppressed both the rise in [Ca2+]i and PGE2 production by PTSMC in
      response to bradykinin, and also significantly suppressed bradykinin-stimulated
      release of radioactivity from PTSMC prelabeled with 3H-labeled arachidonic acid
      (3H-AA). When PTSMC pretreated with dexamethasone were incubated with 170 nM
      prostaglandin H2 (PGH2) or 20 microM arachidonic acid; PTSMC synthesized less
      PGE2 than control PTSMC. Results suggest that bradykinin stimulates PTSMC to
      produce PGE2 via the signal transduction system including Ca2+, and dexamethasone
      appeared to suppress PGE2 production by reducing the activity of cytosolic
      phospholipase A2 (cPLA2) and PGE2 synthase. However, we failed to demonstrate the
      suppression of the activity of cyclooxygenase in PTSMC by dexamethasone. Since
      the elevation of [Ca2+]i is necessary for the contraction of airway smooth
      muscles, dexamethasone seems to reduce the contraction of airway smooth muscles
      by suppressing the rise in [Ca2+]i and the release of arachidonic acid
      metabolites. Reduced production of arachidonic acid metabolites may also
      contribute to improvement in the bronchial inflammation.

PMID- 8531500
TI  - Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth
      muscle.
AB  - Bradykinin (10(-8) - 10(-5) M) caused a concentration-dependent increase in
      cyclic GMP (cGMP) production in bovine tracheal smooth muscle in the absence of
      epithelium. The effect was calcium-dependent and was inhibited by pyrogallol (10
      microM) and methylene blue (10 microM). The inhibition of pyrogallol was reversed
      by superoxide dismutase (100 U/ml). Nitric oxide (NO) synthase inhibitors, NG
      methyl-L-arginine (10-100 microM) and NG-nitro-L-arginine (10-100 microM) reduced
      cGMP accumulation induced by bradykinin in a concentration-dependent fashion, and
      the inhibition was reversed by L-arginine. Immunohistochemistry with a specific
      antibody against neuronal NO synthase from rat cerebellum showed positive
      staining localized in some nerve fibers. Bradykinin-induced cGMP accumulation
      appears to be related to the release of NO, part of which is probably synthesized
      in nonadrenergic noncholinergic nerve in bovine trachea.

PMID- 8531501
TI  - Does an Epstein-Barr viral infection influence the pathogenesis of a primary
      pulmonary B-cell lymphoma?

PMID- 8531502
TI  - Mammalian bombesin receptors.

PMID- 8531503
TI  - Development of imaging agents for the dopamine transporter.

PMID- 8531504
TI  - Human leukocyte interferon alpha: structure, pharmacology, and therapeutic
      applications.

PMID- 8531505
TI  - In vitro digital cell image analysis of morphonuclear modifications induced by
      natural DNA-interacting anticancer drugs in three neoplastic cell lines.
AB  - The effects of seven natural anticancer drugs acting through interaction with DNA
      were characterized at three levels: cell proliferation, cell cycle kinetics and
      chromatin texture. These drug-induced effects were monitored in vitro by means of
      the digital cell image analysis which provides 15 morphonuclear parameters. In
      terms of cell proliferation, results show that the drug-induced effects ranged
      from 10(-11)M to 10(-6)M. With respect to the cell cycle kinetics, the results
      show that the drugs induced an accumulation of the cells in the G2 phase.
      Concerning the chromatin levels, the results show that it is possible to classify
      the drugs according to their mechanism of action on the basis of the multivariate
      analysis of the 15 parameters.

PMID- 8531506
TI  - Influence of free or liposomal amphotericin B on killing of Candida species by
      human peritoneal macrophages.
AB  - The influence of free and liposomal amphotericin B at subinhibitory and
      inhibitory concentrations on killing of Candida albicans (ATCC 10231), Candida
      tropicalis (ATCC 13803) and Cryptococcus neoformans (930) by human peritoneal
      macrophages was investigated in vitro. Peritoneal macrophages were harvested from
      overnight peritoneal dialysate of 10 patients undergoing regular continuous
      ambulatory peritoneal dialysis and incubated with Candida species (1:2), pooled
      human serum, fetal calf serum, Medium 199 and Sabouraud broth (with or without
      amphotericin B) for 6 hours. The killing of Candida species was determined using
      subculture technique. The combination of amphotericin B (free or liposomal) with
      peritoneal macrophages enhanced the killing of the Candida species. Candidacidal
      activity of free and liposomal amphotericin B resulted in comparable effects;
      however, the killing of the yeasts by liposomal amphotericin B was slower than by
      free amphotericin B.

PMID- 8531507
TI  - The effect of flumazenil on CNS oxygen toxicity in the rat.
AB  - The toxicity of hyperbaric oxygen in the central nervous system is expressed by
      generalized tonic-clonic seizures. In the search for drugs effective against
      these seizures, we tested flumazenil, a benzodiazepine antagonist known to have
      antiepileptic properties. Forty rats with chronic cortical electrodes were
      injected i.p. with one of three doses of flumazenil (0.2, 2, and 20 mg/kg) or
      their vehicle, before exposure to 0.5 MPa oxygen. EEG and the spectral analysis
      of background EEG activity were monitored. The duration of the latent period
      until the appearance of electrical discharges in the EEG was used as an index of
      oxygen toxicity. Significant prolongation of the latent period preceding oxygen
      seizures was noted in the group of rats treated with 0.2 mg/kg flumazenil (p <
      0.05 in Tukey test). However, when the dose of flumazenil was increased, the
      duration of the latent period returned to control values. These diverse effects
      of flumazenil on the benzodiazepine receptor may account for its complex effects
      on hyperoxic-induced seizures.

PMID- 8531508
TI  - Higher environmental temperature: effect of multiple exposures on long-term
      diazepam-induced changes in brain regional GABA.
AB  - The measurement of steady state level and accumulation rate of GABA and the
      activities of GAD and GABA-T in brain regions of adult male albino rats treated
      with diazepam (diazepam, 5 mg/kg/day, i.p.) and/or exposed (2 h/day) to higher
      environmental temperatures (higher environmental temperature, 40 degrees C) under
      long-term conditions (7-30 consecutive days) shows that long-term treatment with
      diazepam (5 mg/kg/day, i.p., for 15-30 consecutive days) reduced the GABAergic
      activity in the hypothalamus, corpus striatum (CS) and cerebellum (CM) without
      any alteration in the cerebrocortical region (CC). Multiple exposures to higher
      environmental temperatures for 7 consecutive days, on the other hand, enhanced
      GABAergic activity in hypothalamus, corpus striatum and cerebrocortical region of
      the rat. This higher environmental temperature-induced increase in GABAergic
      activity was further enhanced in the hypothalamus, but it was attenuated in the
      corpus striatum and became normalized in the cerebrocortical region upon the
      prolongation of exposure (15-30 consecutive days) to higher environmental
      temperature. The long-term diazepam-induced inhibition in GABAergic activity in
      hypothalamus and corpus striatum (but not in the cerebellum) disappeared and was
      finally activated following exposures (2 h/day) to higher environmental
      temperatures (40 degrees C) along with diazepam-treatment (5 mg/kg day, i.p.) for
      7, 15 and 30 consecutive days. In the cerebellum, multiple exposures to higher
      environmental temperature did not significantly alter the long-term diazepam
      induced inhibition of GABAergic activity or GABAergic activity in the normal
      rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531509
TI  - Relative bioavailability of DL-oxyfedrine HCl after single-dose oral
      administration of tablets as compared to equimolar solutions.
AB  - The pharmacokinetics and comparative bioavailability of oxyfedrine after single
      dose oral administration of oxyfedrine*HCl tablets in comparison to an equimolar
      aqueous solution of oxyfedrine*HCl were investigated in 12 healthy male subjects.
      Six of them received 96 mg DL-oxyfedrine*HCl as tablets and solution and the
      remaining 6 subjects received 16 mg DL-oxyfedrine*HCl as tablets and solution in
      a randomized cross-over design. For evaluation of the relative bioavailability of
      the tablet formulation, the main metabolite norephedrine (expressed as
      hydrochloride) was analyzed in plasma for all 12 subjects. Furthermore, for
      determination of the parent drug, samples of whole blood were analyzed for DL
      oxyfedrine*HCl. Relevant concentrations of the parent drug were found only in the
      high dosage group. There was no evidence of dose-linearity referring to AUC and
      Cmax of norephedrine between 16-mg and 96-mg doses of DL-oxyfedrine*HCl. The
      relative bioavailability of the tablet formulation after administration of 16 mg
      DL-oxyfedrine*HCl, based on the metabolite norephedrine*HCl was for AUC: 85.37%
      within a 90% confidence interval of 69.29-105.17% and for Cmax: 78.79% within a
      90% confidence interval of 59.19-104.90%. The figures for the 96 mg dose strength
      were: AUC: 107.85% (90.06-129.15%) and for Cmax: 74.74% (62.48-89.42%).

PMID- 8531510
TI  - Recent advances in neuropharmacology of the centrally acting antitussive drugs.

PMID- 8531511
TI  - Brain electrical activity in neurogerontology and psychogeriatric disorders.

PMID- 8531513
TI  - [Market-oriented steering systems were not effective in health care].

PMID- 8531514
TI  - [District physicians work overtime daily].

PMID- 8531515
TI  - [How do insurance companies handle medical certificates? Four physicians report
      their experience].

PMID- 8531516
TI  - [What will direct future drug utilization? Rational knowledge or police
      control?].

PMID- 8531518
TI  - [An inspiring course in ophthalmology in the USA is recommended].

PMID- 8531517
TI  - [Spreading of myths about mental hospitals. Where did the search for knowledge
      disappear?].

PMID- 8531519
TI  - [We do not want neighbourhood microbiological laboratories!].

PMID- 8531520
TI  - [Patients are pleased to be answer questions].

PMID- 8531521
TI  - [Deeper analysis of the selenium study].

PMID- 8531522
TI  - [Compare indoor air quality in Eastern Europe and here].

PMID- 8531523
TI  - [Inguinal hernia, one more time].

PMID- 8531524
TI  - [Nickel sensitization caused by a device used in treatment of hematoma under a
      nail?].

PMID- 8531525
TI  - [Overestablishing of expensive diagnostic services].

PMID- 8531526
TI  - [The need for care of patients with available health care services provided by
      counties or municipalities].

PMID- 8531527
TI  - [The importance of preventing smoking by women. Especially, smoking during
      pregnancy!].

PMID- 8531528
TI  - [Depression caused by beta blockaders. Unknown mechanisms behind well-known
      adverse effects].

PMID- 8531529
TI  - [Percutaneous internal drainage. A safe treatment of pancreatic pseudocysts].

PMID- 8531530
TI  - [A survey of drug administration via infusion pumps. Morphine is the most
      frequently used drug administered by infusion pump].

PMID- 8531531
TI  - [Early athetosis disclosed the function of the corpus striatum. Cecile Vogt
      described the syndrome].

PMID- 8531532
TI  - [Adhesion molecules--a hot research field. A possible target for therapy of
      different diseases].

PMID- 8531533
TI  - [The first national day of psychiatry. The aim is to abolish prejudice and to
      inform about help possibilities].

PMID- 8531534
TI  - [Ectopic pregnancy. The "epidemic" seems to be over].
AB  - Since decades the incidence of ectopic pregnancy has risen in most western
      countries including four to five folded increased rates, suggesting an
      "epidemic". Increasing incidences of ectopic pregnancy was reported in Sweden
      until 1988 and 1989 when a peak of 17.3 cases of ectopic pregnancy/10,000 women
      in fertile age was registered. Between 1990 and 1991 the incidence decreased from
      16.8 to 14.9 cases of ectopic pregnancy/10,000 women. The mortality in Sweden
      1985-1991 was 0.15/1000 (3 deaths in 20,486 cases of ectopic pregnancy), the
      lowest case-fatality rate ever reported.

PMID- 8531535
TI  - [Smoking during pregnancy is harmful for the child].

PMID- 8531536
TI  - [Improved cancer survival in Sweden?].

PMID- 8531537
TI  - [Statistics in medical research. Applications are often unprofessional].

PMID- 8531538
TI  - Reviews 1995.

PMID- 8531539
TI  - Pandora and the problem of evil.

PMID- 8531540
TI  - Prospective validation of artificial neural network trained to identify acute
      myocardial infarction.
AB  - BACKGROUND: Artificial neural networks apply non-linear statistics to pattern
      recognition problems. One such problem is acute myocardial infarction (AMI), a
      diagnosis which, in a patient presenting as an emergency, can be difficult to
      confirm. We report here a prospective comparison of the diagnostic accuracy of a
      network and that of physicians, on the same patients with suspected AMI. METHODS:
      Emergency department physicians who evaluated 1070 patients 18 years or older
      presenting to the emergency department of a teaching hospital in California, USA
      with anterior chest pain indicated whether they thought these patients had
      sustained a myocardial infarction. The network analysed the patient data
      collected by the physicians during their evaluations and also generated a
      diagnosis. FINDINGS: The physicians had a diagnostic sensitivity and specificity
      for myocardial infarction of 73.3% (95% confidence interval 63.3-83.3%) and 81.1%
      (78.7-83.5%), respectively, while the network had a diagnostic sensitivity and
      specificity of 96.0% (91.2-100%) and 96.0% (94.8-97.2%), respectively. Only 7% of
      patients had had an AMI, a low frequency but typical for anterior chest pain.
      INTERPRETATION: The application of non-linear neural computational analysis via
      an artificial neural network to the clinical diagnosis of myocardial infarction
      appears to have significant potential.

PMID- 8531541
TI  - Double-blind controlled trial of effect of housedust-mite allergen avoidance on
      atopic dermatitis.
AB  - BACKGROUND: The role of housedust-mite (HDM) allergen (Der p1) in the
      pathogenesis of atopic dermatitis is controversial. We tested the hypothesis that
      atopic dermatitis improves if amounts of HDM allergen in the home are reduced.
      METHODS: Active treatment comprised Goretex bedcovers (placebo, cotton covers),
      benzyltannate spray (placebo, water), and a high-filtration vacuum cleaner
      (placebo, a conventional domestic vacuum cleaner). Dust was sampled monthly from
      the mattress covers and bedroom and living-room carpets. 48 patients (24 adults
      [mean age 30] and 24 children [mean age 10]) completed the 6-month study. 28 were
      in the active treatment group and 20 in the placebo group. FINDINGS: The weight
      of dust collected from Goretex-covered mattresses had fallen by 98% at 1 month
      (from 386 to 9 mg/m2) with no change thereafter. Placebo covers caused a smaller
      reduction in dust load (361 to 269 mg/m2); the difference between active and
      placebo covers at 6 months was highly significant (p = 0.002). Both active and
      placebo treatments caused significant reductions in Der p1 concentrations in
      bedroom and living-room carpets and the differences between the treatments were
      not significant. The severity of eczema decreased in both groups, but the active
      group showed significantly greater improvements in severity score (difference
      between mean final scores 4.3 units, p = 0.006) and area affected (difference
      between mean final areas 10%, p = 0.006) in analysis of covariance with initial
      mattress dust weights and bedroom carpet Der p1 load as covariates. Reported
      analysis with final values for the covariates showed that most of the treatment
      effect was due to the reduction in mattress dust and carpet Der p1.
      INTERPRETATION: The activity of atopic dermatitis can be greatly reduced by
      effective HDM avoidance. Methods to identify individuals who will benefit most
      from such measures are needed.

PMID- 8531542
TI  - Effect of caffeine on recognition of and physiological responses to hypoglycaemia
      in insulin-dependent diabetes.
AB  - BACKGROUND: For the patient with diabetes, hypoglycaemia unawareness--ie, the
      warning signs of falling blood glucose are missing--is potentially dangerous. One
      study has suggested that, in healthy volunteers, caffeine might be a helpful
      treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the
      brain--namely, a decrease in cerebral blood flow and an increase in brain glucose
      use--to see if the recognition of and physiological responses to hypoglycaemia
      were altered in patients with insulin-dependent diabetes mellitus (IDDM).
      METHODS: 12 patients were studied twice. A hyperinsulinaemic glucose clamp was
      used to maintain plasma glucose at 5 mmol/L for 90 min, followed by 60 min at 3.8
      mmol/L, and then 2.8 mmol/L for a further hour. After 30 min at 5 mmol/L,
      patients consumed, in a double-blind, crossover design, 250 mg caffeine or
      matched placebo. We recorded middle cerebral artery velocity (VMCA),
      counterregulatory hormone levels, and cognitive function, and patients recorded
      hypoglycaemia symptoms on a visual analogue scale. RESULTS: Caffeine caused an
      immediate and sustained fall in VMCA of 10 cm/s, from 60 to 50 cm/s (95% CI -5 to
      -15 cm/s; p < 0.001). At a blood glucose of 3.8 mmol/L, plasma adrenaline levels
      were twice as high after caffeine than after placebo (difference 524 pmol/L).
      When glucose was lowered to 2.8 mmol/L, caffeine ingestion was associated with:
      greater awareness of hypoglycaemia in 9 patients, significantly more intense
      autonomic and neuroglycopenic symptoms, and higher levels of adrenaline,
      cortisol, and growth hormone. Cognitive function (latency of P300 evoked
      potentials) deteriorated to the same extent in both studies at this glucose
      level. INTERPRETATION: The sustained fall in VMCA and augmented sympathoadrenal
      and symptomatic responses during moderate hypoglycaemia suggest caffeine as a
      potentially useful treatment for diabetic patients who have difficulty
      recognising the onset of hypoglycaemia.

PMID- 8531543
TI  - Bed-sharing and sudden infant death.

PMID- 8531544
TI  - Pyronaridine: a promising drug for Africa?

PMID- 8531545
TI  - Randomised trial of pyronaridine versus chloroquine for acute uncomplicated
      falciparum malaria in Africa.
AB  - BACKGROUND: The spread of chloroquine resistance poses a serious problem in
      Africa, where falciparum malaria transmission is the highest in the world.
      Pyronaridine, an acridine derivative, has been used successfully to treat malaria
      in China for over 20 years. We compared the efficacy of pyronaridine and
      chloroquine in African adult patients with acute uncomplicated falciparum malaria
      in Yaounde, Cameroon, where chloroquine resistance is well established. METHODS:
      96 patients were randomly assigned treatment with chloroquine 25 mg/kg or
      pyronaridine 32 mg/kg, both orally and divided over 3 days. Patients were
      followed up for at least 14 days on an outpatient basis. Analysis was by on
      active-treatment. FINDINGS: After losses from follow-up (11) or because of self
      medication with quinine (four), 41 patients treated with chloroquine and 40
      treated with pyronaridine were analysed. Parasite clearance during the 14-day
      follow-up with chloroquine and pyronaridine was 44% and 100%, respectively. All
      patients treated with pyronaridine were afebrile by day 3, and parasitaemia
      cleared by day 4. No serious drug-related side-effects were noted in pyronaridine
      treated patients. INTERPRETATION: Pyronaridine was rapidly effective and well
      tolerated in African patients with acute, uncomplicated falciparum malaria and
      may represent an alternative drug against chloroquine-resistant malaria.

PMID- 8531546
TI  - Idiopathic dysautonomia treated with intravenous gammaglobulin.
AB  - BACKGROUND: A previously healthy 23-year-old man presented with a short history
      of abdominal pain and diarrhoea followed by blurred vision, severe postural
      hypotension, reduced sweating and unremitting fever. METHODS: Examination
      revealed fixed dilated pupils, impaired sweating and postural hypotension.
      Clinical and neurophysiological examination showed no motor or sensory deficit. A
      diagnosis of idiopathic autonomic neuropathy was made. He became gravely ill with
      profound life-threatening hypotension and a prolonged ileus. FINDINGS: Within 36
      h of receiving intravenous gammaglobulin (IVGG) his pupillary areflexia and
      severe hypotension resolved. 2 weeks later the autonomic failure recurred but
      again responded to treatment with IVGG. IVGG is a recognised treatment for
      Guillain-Barre syndrome. INTERPRETATION: This case report demonstrates that IVGG
      is also effective in the rare pure dysautonomic variant.

PMID- 8531547
TI  - Citizen health.

PMID- 8531548
TI  - A soldier in respiratory distress.

PMID- 8531549
TI  - Addiction: brain mechanisms and their treatment implications.

PMID- 8531550
TI  - Lessons from John Graunt.

PMID- 8531551
TI  - I believe therefore I practise.

PMID- 8531552
TI  - Unifying hypothesis for inflammatory bowel disease and associated colon cancer:
      sticking the pieces together with sugar.

PMID- 8531553
TI  - Things that go red in the urine; and others that don't.

PMID- 8531554
TI  - Maturity in medical students.

PMID- 8531555
TI  - Maturity in medical students.

PMID- 8531556
TI  - Maturity in medical students.

PMID- 8531557
TI  - Interleukin-1 in acute myocardial infarction.

PMID- 8531558
TI  - Maturity in medical students.

PMID- 8531559
TI  - Haemorrhagic fever with renal syndrome in north-east Bosnia.

PMID- 8531560
TI  - Hantavirus pulmonary syndrome-related virus from Bolivia.

PMID- 8531561
TI  - Response to IFN alpha in myelogenous leukaemia.

PMID- 8531562
TI  - Exit linoleic acid too?

PMID- 8531563
TI  - World distribution of factor V Leiden mutation.

PMID- 8531564
TI  - World distribution of factor V Leiden mutation.

PMID- 8531565
TI  - World distribution of factor V Leiden mutation.

PMID- 8531566
TI  - World distribution of factor V Leiden mutation.

PMID- 8531567
TI  - Cancer in patients on renal replacement therapy in Lombardy, Italy.

PMID- 8531568
TI  - A physician's life.

PMID- 8531569
TI  - Addiction.

PMID- 8531570
TI  - Secular improvement in self-care independence of old people living in community
      in Kahoku, Japan.

PMID- 8531571
TI  - Vero cytotoxin-producing E coli O157 infection associated with farms.

PMID- 8531572
TI  - Monozygotic twins concordant for response to clozapine.

PMID- 8531573
TI  - Dermatology today.

PMID- 8531574
TI  - Medical privacy.

PMID- 8531575
TI  - Right of overseas doctors to practise in the UK.

PMID- 8531576
TI  - Right of overseas doctors to practise in the UK.

PMID- 8531577
TI  - The ethical type II error.

PMID- 8531578
TI  - Electrical stimulation of sacral nerves for treatment of incontinence.

PMID- 8531579
TI  - High-dose UVA1 for urticaria pigmentosa.

PMID- 8531580
TI  - Creutzfeldt-Jakob disease.

PMID- 8531581
TI  - Creutzfeldt-Jakob disease.

PMID- 8531582
TI  - Creutzfeldt-Jakob disease.

PMID- 8531583
TI  - Creutzfeldt-Jakob disease.

PMID- 8531584
TI  - Barrett's oesophagus and colorectal carcinoma.

PMID- 8531585
TI  - Cyclosporin treatment of hyperimmunoglobulin E syndrome.

PMID- 8531586
TI  - A new Borrelia infecting Lone Star ticks.

PMID- 8531587
TI  - GB-C genomes in a high-risk group, in plasma pools, and in intravenous
      immunoglobulin.

PMID- 8531588
TI  - In praise of descriptive nomenclature.

PMID- 8531590
TI  - Autoimmune hepatitis versus viral hepatitis C.
AB  - Numerous viruses are capable of inducing the syndrome of chronic hepatitis. Among
      them are the hepatitis B, C and D viruses. Out of the most common agents of
      chronic hepatitis, the hepatitis C virus has been found to be strikingly
      associated with autoimmune diseases and serological markers of autoimmunity.
      Conversely, the syndrome of genuine autoimmune hepatitis lacks evidence of
      previous or ongoing virus infection and is diagnosed by additionally excluding
      metabolic, toxic, and genetic causes of chronic hepatitis, and by the response to
      immunosuppressive treatment. This review article summarizes the current knowledge
      of hepatotropic virus-induced autoimmunity. It focuses on the present molecular
      and immunological definitions, the clinical and molecular distinction between
      autoimmune hepatitis and chronic viral hepatitis and the implications for the
      safe and efficacious therapy of these disease entities.

PMID- 8531589
TI  - Infant room-sharing and prone sleep position in sudden infant death syndrome. New
      Zealand Cot Death Study Group.
AB  - BACKGROUND: There is evidence that the risk of sudden infant death syndrome is
      lower among ethnic groups in which parents generally share a room with the infant
      for sleeping. We investigated whether the presence of other family members in the
      infant's sleeping room affects the risk of the sudden infant death syndrome.
      METHODS: The case-control study covered a region with 78% of all births in New
      Zealand during 1987-90. Home interviews were completed with parents of 393 (81.0%
      of total) babies who died from the sudden infant death syndrome aged 28 days to 1
      year and 1592 (88.4% of total) controls, selected from all hospital births in the
      study region. FINDINGS: The relative risk of sudden infant death for sharing the
      room with one or more adults compared with not sharing was 0.19 (95% CI 0.08
      0.45) for sharing at night during the last 2 weeks and 0.27 (0.17-0.41) for
      sharing in the last sleep, after control for other confounders. Sharing the room
      with one or more children did not affect the relative risk (1.25 [0.86-1.82] for
      sharing during last 2 weeks; 1.29 [0.85-1.94] for sharing in last sleep). There
      was a significant interaction (p = 0.033) between not sharing the room with an
      adult and prone sleep position in the last sleep. Compared with infants sharing
      the room with an adult and not prone, the multivariate relative risk was 16.99
      (10.43-27.69) for infants not sharing with an adult and prone, 3.28 (2.06-5.23)
      for infants sharing the room and prone, and 2.60 (1.58-4.30) for infants not
      sharing the room and not prone. The interaction between adult room-sharing and
      prone sleep position suggests that both exposures may affect the risk of sudden
      infant death syndrome through a common mechanism. INTERPRETATION: We recommend
      that infants sleep in the same bedroom as their parents at night to reduce the
      risk of sudden infant death syndrome.

PMID- 8531591
TI  - Benign myxoid hepatocellular tumor: a variant of liver cell adenoma.
AB  - A case of myxoid hepatocellular adenoma in the non-cirrhotic liver of a 26-year
      old man is described. Grossly, the tumor was well circumscribed, rounded and
      measured 16 cm in diameter. Histologically, the tumor was characterized by nests
      and strands of polygonal cells embedded in a myxoid extracellular matrix.
      Electron microscopy confirmed the hepatocellular nature of the neoplastic cells.
      The patient is alive and well, without evidence of disease, 2 years after a local
      excision.

PMID- 8531592
TI  - Short-term cardiovascular effects of somatostatin in patients with cirrhosis.
AB  - Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and
      portal hypertension. Its systemic hemodynamic effects, however, are not yet well
      defined. Since cardiomyopathy or pulmonary artery hypertension may occur in
      patients with cirrhosis, definition of the systemic hemodynamic effects of
      somatostatin or its analogue octreotide is of clinical importance. The aim of
      this study was to evaluate the effects of somatostatin, at different doses and
      under different conditions of administration, on the systemic hemodynamics in 17
      patients with cirrhosis. Two sets of experiments were performed. In the first,
      eight patients received two different bolus doses (100 and 250 micrograms) of
      somatostatin. The second set of experiments was designed to study the hemodynamic
      effects of the combination of a bolus and an infusion of somatostatin. Nine other
      patients received one bolus of 250 micrograms of somatostatin, followed by a 250
      micrograms/h infusion for 65 min. A second bolus of 250 micrograms of
      somatostatin was injected in these patients after 35 min of infusion. Before and
      for 30 min after each bolus, systemic hemodynamics were measured. Following a
      bolus of somatostatin, a dose-dependent decrease in heart rate (from 77 +/- 3 to
      73 +/- 5 beats/min with 100 micrograms, and from 78 +/- 4 to 68 +/- 5 beats/min
      with 250 micrograms, p < 0.05) and increases in systemic and pulmonary artery
      pressures were observed. The combination of an infusion and a bolus of
      somatostatin significantly reduced the increases in systemic and pulmonary artery
      pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531593
TI  - The effect of extrahepatic cholestasis on liver regeneration after partial
      hepatectomy in the rat.
AB  - Liver regeneration after partial hepatectomy was studied in four groups of rats:
      control rats (n = 12), rats with 1 week of common bile duct obstruction (n = 11),
      rats with restoration of bile flow after 1 week of obstruction (n = 9) and a sham
      operated group (n = 7). Parameters of DNA synthesis--thymidine kinase activity
      and in vivo bromodeoxyuridine incorporation--were measured at partial hepatectomy
      (T = 0), and 24 and 48 h after partial hepatectomy. During common bile duct
      obstruction, DNA synthesis was already stimulated at T = 0, but partial
      hepatectomy in common bile duct obstruction rats induced a delayed DNA synthesis.
      After 1 week of restoration of bile flow, normal DNA synthesis had returned at T
      = 0, but DNA synthesis after partial hepatectomy was still delayed. The sham
      operated rats showed a normal regeneration response after partial hepatectomy
      assessed by bromodeoxyuridine incorporation but delayed as assessed by thymidine
      kinase activity, partly due to the impaired physical condition of the animals.
      The present data support the hypothesis that during cholestasis, regeneration
      promoting, and inhibitory factors accumulate in the liver, their balance
      determining whether regeneration after partial hepatectomy will occur in a
      normal, enhanced or delayed way.

PMID- 8531594
TI  - Contact solvents for common bile duct stones. Study in an in vitro system.
AB  - Cholesterol and brown pigment stones found in the common bile duct are often
      radiolucent and therefore indistinguishable. The purpose of this study was to
      define contact solvent systems able to dissolve both stone types. The influence
      of mucolytic agents on in vitro pigment stone dissolution was first determined.
      It was shown that dithioerythritol induced more rapid dissolution than N
      acetylcysteine. Alternating treatment with an aqueous alkaline solvent (pH =
      9.5), composed of sodium deoxycholate 50 mM, ethylenediaminetetraacetate 26 mM
      and dithioerythritol 50 mM, for 45 min, and an organic solvent methyl tert-butyl
      ether/dimethyl sulfoxide (90/10) for 15 min, was more effective for bilirubin,
      cholesterol, and fatty acid solubilization (p < 0.01) than using these solvents
      separately. The dissolution of brown stones was nearly completed within 9 h and
      that of mixed cholesterol stones was obtained within 3 h. We conclude that the
      alternating treatment described is very effective for the rapid in vitro
      dissolution of the two major stone types present in the bile ducts, and deserves
      further assessment in vivo.

PMID- 8531595
TI  - Functional differences between activated and normal rat liver macrophages: LPS
      uptake capacity by flow cytometric analysis in contrast with TNF-alpha release.
AB  - Activated liver macrophages are considered to play an important role in the
      development of liver injuries. Functional differences between activated and
      normal rat liver macrophages were investigated. In addition, from the therapeutic
      point of view, the effects of prostaglandin E1, prostaglandin I2 and E3330 ((2E)
      3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2-nonyl-2-propenoic acid) on the
      functions of liver macrophages were also determined. Rat liver macrophages were
      primed by Propionibacterium acnes and activated by a small dose of
      lipopolysaccharide. Lipopolysaccharide uptake capacity was evaluated
      quantitatively by flow cytometric analysis. Tumor necrosis factor-alpha
      activities were measured by bioassay. There were no significant differences in
      lipopolysaccharide uptake capacity between activated and normal liver
      macrophages, while activated liver macrophages had a significantly (P < 0.01)
      higher capacity in the release of tumor necrosis factor-alpha. Prostaglandin E1
      and E3330 inhibited tumor necrosis factor-alpha release without suppressing
      lipopolysaccharide uptake capacity. In this study we have clarified the
      functional differences between activated and normal liver macrophages. The
      beneficial effects of prostaglandin E1 and E3330 on the functions of liver
      macrophages were also demonstrated.

PMID- 8531596
TI  - Normotest and abnormal prothrombin in liver transplantation.
AB  - Postoperative changes in coagulation parameters, including the abnormal plasma
      prothrombin level, were studied in 95 patients who underwent liver
      transplantation, and the results were compared with the clinical outcome. The
      patients were classified into four groups: Group I had a satisfactory
      postoperative course, (n = 76), Group II suffered graft failure or death at 31
      days or more after transplantation (n = 9); Group III suffered graft failure or
      death from 8 to 30 days after transplantation (n = 4); and Group IV suffered
      graft failure or death within 7 days of transplantation (n = 6). The Normotest,
      which closely reflected liver graft function, showed an increase immediately
      after transplantation in Group I, II, and III, but showed a marked decrease in
      Group IV. In patients with severe acute cellular rejection, the plasma level of
      abnormal prothrombin (des-gamma-carboxy prothrombin) was compared with the
      histology of the liver biopsy specimen. When liver graft function was good after
      orthotopic transplantation, the Normotest value recovered to the normal range of
      70% or more. Subsequently, graft function remained good when the des-gamma
      carboxy prothrombin level stayed low, whereas acute cellular rejection was
      indicated by an elevation of des-gamma-carboxy prothrombin was not produced by
      graft with early failure, the des-gamma-carboxy prothrombin level also remained
      low. Thus, the Normotest value and the des-gamma-carboxy prothrombin level were
      both useful parameters for assessing hepatic function and rejection after
      transplantation.

PMID- 8531597
TI  - High interleukin-6 production within the peritoneal cavity in decompensated
      cirrhosis and malignancy-related ascites.
AB  - To assess the diagnostic and prognostic value of interleukin-6, interleukin 1
      beta, and tumor necrosis factor-alpha assays in plasma and ascites, we measured
      these cytokines in eight patients with malignancy-related ascites and 32 patients
      with decompensated cirrhosis. Five patients had an episode of bacterial
      peritonitis, during which one or more ascitic fluid samples were analyzed.
      Interleukin-6 and tumor necrosis factor-alpha were not significantly different
      between the cirrhotic and the malignant groups: ascitic interleukin-6 13,816 +/-
      15,314 vs 28,138 +/- 23,403 pg/ml, plasma interleukin-6 542 +/- 719 vs 559 +/-
      604 pg/ml; ascitic tumor necrosis factor-alpha 19 +/- 50 vs 12 +/- 31 pg/ml,
      plasma tumor necrosis factor-alpha 3.4 +/- 8.2 vs 6.1 +/- 13.8 pg/ml. During an
      episode of bacterial peritonitis there was a significant increase only in ascitic
      interleukin-6 (133,268 +/- 99,743 pg/ml), which declined after antibiotic
      treatment. None of the parameters was associated with 6-month survival (11 of the
      40 patients died within 6 months). There was a correlation (r = 0.675; p = 0.002)
      between plasma interleukin-6 levels and the Child-Pugh score in patients with
      cirrhosis, but not with the etiology of the liver disorder. Plasma interleukin-6
      levels correlated with IgA levels (r = 0.649; p = 0.004) but not with C reactive
      protein, sedimentation rate, fibrinogen, IgM or IgG. These results do suggest
      that interleukin-6 is produced within the peritoneal cavity in hepatic and
      malignant ascites. There is a sharp increase in the local production of
      interleukin-6 during an episode of bacterial peritonitis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8531598
TI  - 1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1
      naphthylisothiocyanate.
AB  - The importance of the bioactivation of 1-naphthylisothiocyanate was studied.
      Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was
      collected over a 2.5-h period; the liver was then excised and homogenized. 1
      naphthylisothiocyanate and its metabolites in bile and liver of rats were
      identified and quantified using coupled gas chromatography-mass spectrometry.
      Three main compounds were found in all 1-naphthylisothiocyanate-treated animals.
      They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent
      compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which
      attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1
      naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was
      significantly lower than in rats receiving only 1-naphthylisothiocyanate. The
      appearance of 1-naphthylamine was also inhibited by cycloheximide, although not
      to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital,
      which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl
      isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl
      isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1
      naphthylisothiocyanate might be involved in the hepatotoxic effect of 1
      naphthylisothiocyanate.

PMID- 8531599
TI  - Transient hepatic fibrin-ring granulomas in a patient with acute hepatitis A.
AB  - A case of acute hepatitis A associated with fibrin-ring granulomas in the liver
      is presented. Because a relationship between acute hepatitis A infection and
      granuloma formation had not previously been established, liver specimens were
      examined from both the hepatitic and recovery phases. Numerous fibrin-ring
      granulomas were observed in the parenchyma during the hepatitic phase. The
      cellular components of the granulomas were largely macrophages and CD4-positive T
      cells. Granulomas had disappeared completely by the recovery phase. These results
      suggest that fibrin-ring granulomas were caused by hepatitis A virus infection.
      This virus may activate macrophages and CD4-positive T-cells through an as-yet
      undetermined mechanism.

PMID- 8531600
TI  - Protection of patient confidentiality.

PMID- 8531601
TI  - Internet medical publications: publish (electronically) or perish?

PMID- 8531602
TI  - Synthesizing Shewhart and Shannon. Part 1. The diagram.

PMID- 8531603
TI  - Design and implementation of an automated operative note.

PMID- 8531604
TI  - Body composition by DXA: tried and true?
AB  - Dual-energy x-ray absorptiometry (DXA) is unquestionably the method of choice for
      the assessment of bone mass. Recent generations of DXA instruments also have the
      capability of assessing soft tissue mass, thereby providing a three-compartment
      model of body composition, i.e., bone mineral, fat, and bone-free lean masses.
      Although hydrodensitometry has long been considered the reference method of
      assessing body composition, assumptions regarding the constancy of the
      constituents of fat-free mass may compromise its validity in some populations.
      Because DXA appears to be less dependent on assumptions regarding biological
      consistency, it is possible that it has the potential to provide a more accurate
      assessment of body composition across populations than does hydrodensitometry,
      and that it should be considered the reference method. DXA has been shown to
      provide precise measures of body composition, but it remains questionable as to
      whether those measures are accurate. Contributing to the uncertainty regarding
      validity is the variability among manufacturers of DXA instruments in the methods
      of calibration, data acquisition, and data analysis. Although DXA holds great
      promise in becoming the criterion method of assessing body composition, and has
      been promoted as such by some investigators, available data indicate that this
      endorsement is premature.

PMID- 8531605
TI  - Variations in bone status of contralateral and regional sites in young athletic
      women.
AB  - To determine if volleyball (VB), basketball (BB), soccer (SO) and swimming (SW)
      programs were associated with site-specific differences in contralateral,
      regional, and total body bone mineral density (BMD), 62 eumenorrheic female
      athletes [BB (N = 7), VB (N = 11), SO (N = 9), and SW (N = 7)] and controls
      participated in the study. The controls were categorized as either moderately
      active control (MOD) (N = 17) or sedentary control (SED) (N = 11) based on
      fitness and activity assessments. Contralateral, total body, lumbar (L2-L4), and
      femur BMD were measured (Lunar DPX). The between sport contralateral comparisons
      indicated that VB and BB had significantly greater leg and arm measurements than
      all other groups, while the within contralateral comparisons revealed
      significantly greater right arm measurements for all groups, except SW. No
      significant differences were found for the within group contralateral leg
      comparisons, except VB. VB and BB had significantly higher (P < or = 0.05) total
      body and lumbar BMD values than SW, MOD, and SED. At the femur neck, trochanter,
      and Ward's triangle, BB showed significantly higher BMD than SW, MOD, and SED.
      Only BB had significantly higher Ward's triangle BMD than SW, MOD, and SED. Our
      findings show site-specific differences in BMD associated with selected sports'
      programs.

PMID- 8531606
TI  - Electrocardiographic and echocardiographic characteristics of female athletes.
AB  - This study examined electrocardiographic and echocardiographic characteristics of
      endurance- and resistance-trained female athletes. The subjects were 10 varsity
      caliber endurance-trained athletes, 10 resistance-trained athletes, and 10
      nonathletes. Data collection included anthropometric measurements, VO2max,
      standard 12-lead ECGs and left ventricular dimensions measured by M-mode and two
      dimensional echocardiography. For endurance-trained athletes, absolute left
      ventricular end-diastolic volume and values normalized for lean body mass were
      significantly greater than in nonathletes. An interstudy comparison of female vs
      male endurance-trained athletes from the same population also revealed
      significantly lower values for M-mode left ventricular mass expressed per
      kilogram of lean body mass in the former. Absolute and normalized wall
      thicknesses were not significantly greater in resistance-trained athletes
      compared to the other two groups. Wall thickness indexed for lean body mass was
      similar for the three groups. Sinus bradycardia was observed in all endurance
      athletes and in four resistance-trained athletes. ECG criteria were unreliable
      for the prediction of left ventricular enlargement. It appears that both female
      resistance- and endurance-trained athletes exhibit a lesser degree of enlargement
      of left ventricular wall thickness and mass than male athletes. A close
      relationship between skeletal and cardiac muscularity in resistance-trained
      athletes of both genders also was supported.

PMID- 8531607
TI  - Aerobic exercise and normotensive adults: a meta-analysis.
AB  - Using the meta-analytic approach, the purpose of this study was to examine the
      effects of aerobic exercise on resting systolic (SYS) and diastolic (DIA) blood
      pressure in normotensive adults: The results of 35 human clinical training
      studies published in English-language journals between 1963 and 1992 and
      representing 1,076 subjects (800 exercise, 276 control) met criteria for
      inclusion. Across all categories and designs, statistically significant post
      exercise reductions were found for both SYS and DIA blood pressure (mean +/- SD,
      SYS: -4.4 +/- 6.6 mm Hg, 95% CI, -6.2 to -2.6 mm Hg; DIA: -3.2 +/- 3.2 mm Hg, 95%
      CI, -4.0 to -2.2 mm Hg). When partitioned according to type of study: 1)
      (randomized controlled trials (RCT), 2) controlled trials (CT), and 3) no
      controls (NC), the following changes were noted: RCT, SYS: -4.5 +/- 7.2 mm Hg,
      95% CI, -7.1 to -1.2 mm Hg; DIA: -3.8 +/- 2.9 mm Hg, 95% CI, -5.0 to -2.6 mm Hg;
      CT, SYS: -2.8 +/- 6.9 mm Hg, 95% CI, -10.0 to 4.4 mm Hg; DIA: -5.0 +/- 3.7 mm Hg,
      95% CI, -8.9 to -1.1 mm Hg; NC, SYS: -4.7 +/- 6.1 mm Hg, 95% CI, -7.5 to 1.9 mm
      Hg; DIA: -1.7 +/- 3.0 mm Hg, 95% CI, -3.2 to -0.36 mm Hg. We concluded that
      aerobic exercise results in small reductions in resting SYS and DIA blood
      pressure among normotensive adults.

PMID- 8531608
TI  - Effect of intermittent eccentric contractions on symptoms of muscle microinjury.
AB  - The purpose was to determine whether varying the duration of rest between
      contractions affects selected symptoms of eccentric contraction-induced skeletal
      muscle microinjury. Thirty-three women were assigned to three groups (N = 11).
      Each performed one bout of exercise with each arm involving 10 eccentric
      contractions of the elbow flexor muscles, lowering a load equaling 60% of maximal
      static force. One arm exercised continuously; the other exercised with rest
      periods of 15 s, 5 min, or 10 min between contractions, depending on the group.
      Preexercise and 0, 24, and 48 h postexercise, symptoms of microinjury in the
      elbow flexor muscles were assessed: soreness and changes in strength, resting
      elbow angle ("musculotendinous stiffness"), and arm girth ("swelling"). For all
      groups combined, 10 continuous contractions caused changes (P < 0.05) in all
      variables at every measurement time. For example, soreness ratings (0-10 scale)
      were 4.3 +/- 2.0 (24 h) and 4.3 +/- 2.1 (48 h) and strength was reduced 18% 0 h
      postexercise. Responses were similar with 15 s of rest between contractions.
      Although they were moderated, symptoms occurred even with 5 and 10 min of rest.
      With 10 min between contractions, soreness occurred (e.g., 2.4 +/- 1.5 [24 h])
      and strength was 17% reduced 0 h postexercise. Results are most consistent with a
      mechanical cause of eccentric contraction-induced muscle microinjury, rather than
      a metabolic or other factor with a short recovery time, although involvement of
      the latter cannot be ruled out.

PMID- 8531609
TI  - Anabolic-androgenic steroid increases running endurance in rats.
AB  - The study was designed to determine whether treatment with an anabolic-androgenic
      steroid enhances running performance in rats by increasing their freely chosen
      training distance. Forty male Long-Evans rats were randomly divided into either a
      sedentary control group or an exercising group caged in specially designed
      running wheels in which the rats were able to run spontaneously. After 4 wk, both
      groups were further subdivided into two groups receiving either 0.5-mg Durabolin
      (nandrolone phenylpropionate) (im) or 0.5-mg saline, every second day. After 8
      wk, running distance was similar in both exercising groups. Rats receiving the
      anabolic-androgenic steroid ran 41% longer during the test of submaximal running
      endurance compared to the trained rats receiving saline (P < 0.05). Submaximal
      running endurance was not increased in sedentary rats receiving the anabolic
      androgenic steroid. After 4 wk of training, the maximal sprinting speed increased
      by 29% in trained rats. There was no further increase in maximal sprinting speed
      after an additional 4 wk of training and treatment with either anabolic
      androgenic steroid or saline treatment. Therefore, rats that train spontaneously
      while being treated with an anabolic-androgenic steroid had increased submaximal
      running endurance compared with trained rats treated with saline, despite the
      similar voluntary training distance and skeletal muscle oxidative capacity
      between the two groups. The mechanism by which treatment with an anabolic
      androgenic steroid, combined with training, enhances submaximal running
      performance could not be identified and needs to be addressed in future studies.

PMID- 8531610
TI  - Strenuous exercise with caloric restriction: effect on luteinizing hormone
      secretion.
AB  - To test whether strenuous exercise with and without caloric restriction alters LH
      secretion, and whether these changes are apparent in the immediate post-exercise
      period, LH pulse parameters were studied in four moderately trained eumenorrheic
      women over three successive menstrual cycles. Blood samples were obtained 5 h
      before and 5 h after 90 min of running at 74% VO2max. Each test was preceded by a
      7-d treatment of controlled diet and exercise (74% VO2max). During CONTROL,
      subjects were eucaloric on days 1-7, and performed no exercise on days 5-7.
      During STTI (short-term training increase), subjects were eucaloric and completed
      90 min runs on days 5-7. During DIET/STTI, subjects consumed 60% of the calories
      necessary to maintain weight on days 1-7, and exercised as in STTI. A significant
      decrease in overall (0700-1830 h) LH pulse frequency during DIET/STTI compared
      with CONTROL and STTI treatments was observed. No changes were found in mean
      serum LH levels or peak amplitude. These results suggest that high-volume
      training combined with caloric restriction may predispose one to exercise-induced
      changes in LH pulse frequency, while adequate caloric intake may prevent these
      changes.

PMID- 8531611
TI  - Enhanced cardiopulmonary reflex inhibition of heart rate during exercise.
AB  - We tested the hypothesis that the reflex inhibition of heart rate (HR) during
      mechanical (acute bolus injection of 0.5% and 2% of estimated blood volume) and
      chemical (phenylbiguanide, PBG, 2.5 and 5 micrograms.kg-1) stimulation of
      cardiopulmonary receptors would be enhanced during exercise. Rats were
      instrumented with arterial and venous catheters. The reflex response to
      mechanical (N = 7) and chemical (N = 8) stimulation of cardiopulmonary receptors
      was examined at rest and during exercise (6 m.min-1, 10% grade). A two-way
      analysis of covariance (ANCOVA) with repeated measures was used to test for
      differences in the reflex regulation of HR at rest vs exercise. HR was used as
      the covariate because exercise significantly increased baseline HR. There was no
      significant treatment effect (rest vs exercise) for the reflex inhibition of HR
      during mechanical stimulation. However, the two-way ANCOVA revealed a significant
      treatment effect (rest vs exercise) for the reflex inhibition of HR during
      chemical stimulation. The reflex decreases in HR were enhanced (-delta 23 +/- 8
      vs -delta 133 +/- 47 and -delta 208 +/- 40 vs -delta 374 +/- 10 bpm at 2.5 and 5
      micrograms.kg-1, respectively). These data suggest that factors associated with
      exercise enhanced the cardiopulmonary reflex inhibition of heart rate during
      chemical stimulation.

PMID- 8531613
TI  - Effect of sodium concentration in a carbohydrate-electrolyte solution on
      intestinal absorption.
AB  - Intestinal absorption during infusion (15 ml.min-1) of a 6% carbohydrate (2%
      glucose and 4% sucrose) solution containing either 0, 25 or 50 mEq.l-1 Na+ was
      measured by segmental perfusion with a triple lumen tube in males (age 24.3 +/-
      1.6) at rest in a neutral environment (22 degrees C). Infusion of the 25 and 50
      mEq.l-1 Na+ solutions was performed using a balanced design on the same day,
      separated by a 1-hr period of no infusion. Infusion of 0 mEq.l-1 Na+ solution was
      performed on a separate day. A 45-min equilibration period preceded a 90-min test
      session. Water and solute fluxes were determined from differences in
      concentration of polyethylene glycol and solute across a 40-cm intestinal segment
      of the duodenojejunum. A two-factor repeated measures ANOVA indicated no
      differences (P > 0.1) over time for water, Na+, or glucose flux for all
      solutions. Plasma volume increased (P < 0.01) approximately 5% over time for all
      solutions. We conclude that Na+ concentrations of 0, 25, or 50 mEq.l-1 in a 6%
      carbohydrate solution have similar effects on the absorption of water, Na+, and
      glucose from the duodenojejunum. Glucose in the infusion solution is the more
      important factor determining intestinal water absorption than Na+. This study
      suggests that adding Na+ to fluid replacement beverages may not be a factor in
      fluid absorption.

PMID- 8531612
TI  - Autonomic nervous system control of the heart: endurance exercise training.
AB  - The purpose of this study was to assess hemodynamic responses to lower body
      negative pressure (LBNP) to -45 torr with selective cardiac parasympathetic
      (using atropine sulphate), sympathetic efferent (using metoprolol tartrate), and
      combined (atropine+metoprolol) blockade prior to and following 8 months of
      endurance exercise training in eight young men. Training resulted in significant
      increases of maximal oxygen uptake (27%) and blood volume (16%) and a decrease of
      baseline heart rate (HR, from 66 +/- 4 to 57 +/- 4 bpm). This training related
      bradycardia was exclusively determined by an enhanced vagal tone as there was no
      significant difference in intrinsic HR pre- to post-training and only atropine
      (pre: 100 +/- 3 vs post: 101 +/- 3 bpm), not metoprolol (pre: 56 +/- 3 vs post:
      49 +/- 4 bpm), abolished the HR difference. The reflex tachycardia in the control
      experiment was significantly diminished following training. However, the increase
      in HR at LBNP -45 torr between pre- and post-training was similar after either
      atropine (+13 +/- 2 vs +14 +/- 1 bpm) or metoprolol (+8 +/- 1 vs +8 +/- 1 bpm).
      Reflex tachycardia was greater during atropine than metoprolol blockade and the
      sum of the HR increase during selective blockade (21 and 22 bpm) was greater when
      compared with the control (no blockade, 16 +/- 2 vs 11 +/- 2 bpm). There was no
      difference pre- to post-training in SV or Qc response to -45 torr LBNP during the
      control condition. However, selective beta 1-receptor blockade resulted in a
      greater decrease in SV to -45 torr LBNP post-training compared to pre-training (P
      < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531614
TI  - Changes in magnetic resonance transverse relaxation times of two muscles
      following standardized exercise.
AB  - Magnetic resonance (MR) imaging studies of exercising leg muscles were performed
      to compare the changes in MR transverse relaxation times (T2) that result from
      exercise of the anterior tibialis (AT) and extensor digitorum/hallicus longus (E)
      in the anterior compartment of the lower leg with those T2 changes in the medial
      and lateral gastrocnemius (G) in the posterior compartment. Spin-echo MR images
      were obtained at 1.5 Tesla before and during the first 14 min of recovery from
      dynamic exercise. In order to normalize the exercise, workloads for each subject
      were set at 25% of the measured maximum voluntary contraction (MVC) of the
      anterior and posterior compartments. In separate exercise sessions, a
      nonmagnetic, pneumatic exercise apparatus was employed for either dorsiflexion or
      plantarflexion against a fixed constant resistance for two different exercise
      durations (1 min 45 s or 5 min). Transaxial MR images (TR = 1000 ms, TE = 30, 60,
      90, 120 ms, 128 x 256 matrix, 1.5 cm slice) were used to calculate T2 values.
      Although subjects performed approximately 7-fold more work (P < or = 0.001,
      dorsiflexion vs plantarflexion) during plantarflexion than during dorsiflexion at
      both exercise duration's, the exercise induced T2, while being greater than those
      at rest (P < or = 0.001), were not significantly different in the different
      compartments. We conclude that, when exercised at the same workload (25% of MVC),
      these two muscles produce T2 changes that are not significantly different from
      each other.

PMID- 8531615
TI  - Estimation of critical power with nonlinear and linear models.
AB  - Sixteen young, healthy males each performed five to seven randomly assigned,
      exhaustive exercise bouts on a cycle ergometer, with each bout on a separate day
      and at a different power, to compare estimates of critical power (PC) and
      anaerobic work capacity (W') among five different models: t = W'/(Pmax-PC) (two
      parameter nonlinear); t = (W'/P-PC))-(W'/(Pmax-PC)) (three-parameter nonlinear);
      P.t = W' + (PC.t) (linear (P.t)); P = (W'/t) + PC (linear (P)); P = PC + (Pmax
      PC)exp(-t/tau) (exponential). The data fit each of the models well (mean R2 =
      0.96 through 1.00 for each model). However, significant differences among models
      were observed for both PC (mean +/- standard deviation (SD) for each model was
      195 +/- 29 W through 242 +/- 21 W) and W' (18 +/- 5 kJ through 58 +/- 19 kJ). PC
      estimates among models were significantly correlated (r = 0.78 through 0.99). For
      W', between-model correlations ranged from 0.25 to 0.95. For a group of six
      subjects, the ventilatory threshold for long-term exercise (LTE Tvent; 189 +/- 34
      W) was significantly lower than PC for all models except the three-parameter
      nonlinear (PC = 197 +/- 30 W); PC for each model was, however, positively
      correlated with LTE Tvent (r = 0.69 through 0.91).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8531616
TI  - Comparison of body composition between German and American adults with mental
      retardation.
AB  - Several studies have confirmed that there is a high incidence of obesity among
      adults with mental retardation (MR) living in the United States. However, there
      has never been a systematic comparison of the anthropometric characteristics
      between adults with MR from different countries. The purpose of this study was to
      compare the body composition levels of 210 adults with MR residing in two
      different residential settings in the United States and in Germany. Subjects'
      mean age was 31.7 yr. Skinfold measurements were used to estimate percent body
      fat (PBF), and height and weight were used to compute body mass index (BMI).
      Results indicated that PBF was significantly higher among females (P < 0.001);
      subjects in the institutional setting had significantly lower PBF and BMI levels
      than subjects in the family setting (P < 0.001); and PBF and BMI levels were
      significantly higher in subjects from the United States compared with the German
      subjects (P < 0.001). These findings indicate a need for further investigation
      into the caloric intake, energy expenditure, lifestyle, and metabolic
      characteristics of adults with MR living in the United States and Germany.

PMID- 8531617
TI  - Does strength training inhibit gains in range of motion from flexibility training
      in older adults?
AB  - Thirty-one untrained men between the ages of 50 and 74 (61 +/- 6 yr, mean +/- SD)
      were studied to compare the effects of strength and flexibility (SF) training,
      flexibility only (FO) training, and no training (inactive control group) on
      shoulder and hip range of motion. Fourteen of these subjects volunteered to
      participate in an SF training program three times per week for 10 wk. Ten others
      participated in an FO training program during this same time period, and the
      remaining seven subjects agreed to serve as an inactive control group by not
      participating in any regular exercise. The SF training consisted of a 3-min warm
      up on a stationary bike, approximately 30 min of heavy resistance strength
      training, and about 10 min of static stretches performed before and after each
      training session. Maximal oxygen uptake (VO2max), percentage of body fat, and
      muscular strength (three-repetition maximum and peak isokinetic torque) were
      assessed before and after training for the SF group. Shoulder abduction, shoulder
      flexion, and hip flexion were measured with a universal goniometer in all groups
      before and after the training period. The FO training consisted of the identical
      warm-up and stretching exercises used in the SF training but without strength
      training. The results indicate that the FO group increased its range of motion in
      shoulder abduction to a significantly greater extent than the SF group (P <
      0.001), and none of the changes in range of motion for the SF group was
      significantly different than the changes in the control group.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8531618
TI  - Predictive accuracy of bioimpedance equations in estimating fat-free mass of
      Hispanic women.
AB  - This study assessed the predictive accuracy of previously published bioelectrical
      impedance analysis equations for estimating fat-free mass of young (20-39 yr)
      Hispanic women (N = 29). The reference method was hydrostatic weighing at
      residual lung volume. Body density was converted to percent body fat using the
      Siri equation. Resistance and reactance were measured with a Valhalla
      bioimpedance analyzer. The bioelectrical impedance analysis equations of Lohman,
      Rising, Stolarczyk, Segal, Gray, and Van Loan were cross-validated. There were
      significant correlations between criterion and predicted fat-free mass (r = 0.86
      0.95) for all equations. The standard error of estimate for each equation was
      acceptable; however, the total error for the Stolarczyk (3.2 kg) and the Van Loan
      (4.6 kg) equations exceeded the recommended value (2.8 kg). For all equations,
      the difference between average criterion and predicted fat-free mass was
      significant (P < 0.05). However, the mean differences for the Lohman (0.8 kg),
      Segal (0.8 kg), and Gray (0.9 kg) equations were small. In conclusion, the Segal,
      Lohman, and Gray equations may have potential for assessing the body composition
      of healthy, acculturated, Hispanic women.

PMID- 8531619
TI  - Validation of a cycle ergometry equation for predicting steady-rate VO2 in obese
      women.
AB  - The purpose of this study was to determine the accuracy of equations developed by
      the American College of Sports Medicine and by Latin et al. (Med. Sci. Sports
      Exerc. 25:970-974, 1993) for estimating the oxygen cost of cycle ergometry in
      obese women. Fifty-six deconditioned subjects, aged 23-60 yr, performed a three
      stage (0, 50, and 100 W) submaximal cycle ergometry test while their oxygen
      uptake was measured. Results indicated that the ACSM equation significantly (P <
      0.05) underestimated oxygen consumption at all three workloads. The Latin
      equation, by contrast, correctly predicted oxygen consumption at the 50- and 100
      W workloads, although not at 0 load. The mean bias for all three workloads was
      287.6 ml.min-1 for the ACSM equation and 58.3 ml.min-1 for the Latin equation.
      These data suggest that the Latin equation is more accurate than the ACSM formula
      for estimating oxygen consumption of loaded cycling in obese women. However,
      caution must be used when attempting to predict the caloric cost of unloaded
      cycling.

PMID- 8531620
TI  - Post-swim orthostatic intolerance in a marathon swimmer.
AB  - Two swims (1993 and 1994) are described which led to post-swim orthostatic
      intolerance and one episode of syncope in a 50/51-yr-old well-trained and
      experienced marathon swimmer. The swims of 33 km and 38 km took 12 h 30 s and 17
      h 35 min, respectively. Water temperature in each swim was above 23 degrees C and
      rectal core-temperature stayed above 37.0 degrees C. Air temperatures differed,
      ranging from 23 degrees to 37 degrees C and 15 degrees to 21 degrees C,
      respectively. Regular fluid consumption totalled approximately 5.0 and 6.0 1,
      respectively. Fifteen minutes after completing the 1993 swim, the swimmer
      experienced orthostatic intolerance and fainted at the lakeside; hospital tests
      revealed an elevated creatine phosphokinase (CK) of 521 U.l-1. The 1994 swim was
      abandoned due to severe muscle cramps and CK was found to be markedly elevated at
      909 U.l-1. Orthostatic intolerance was recorded in both cases; however, no
      cardiac abnormalities were found. After overnight rest and intravenous saline
      infusions of 3.0 and 1.5 l, respectively, the orthostatic intolerance was
      relieved. Based on previous descriptions of exercise-associated collapse in
      marathon runners, the swimmer's orthostatic intolerance and syncope are
      attributed to blood pooling in his legs due to inactivation of the venous muscle
      pump on completion of the swim.

PMID- 8531621
TI  - Exercise-associated collapse in cyclists is unrelated to endotoxemia.
AB  - Endotoxemia occurs when intestinal ischemia allows bacterial lipopolysaccharide
      to translocate from colonic flora into the bloodstream, which triggers release of
      cytokines that can cause hypotension, rigors, fever, shock, and even death.
      Recently, blood endotoxin levels were shown to be higher in athletes needing
      medical attention (330 pg.ml-1) than in their competitors with similar
      performances (81 pg.ml-1). Though there were no data showing that these athletes
      had elevated core temperatures or severe illness, speculation followed that
      endotoxin may play a causal role in heat stroke. We examined the relationship
      between endotoxemia and mild post-exertional illness in 39 cyclists after a 100
      mile ride. Thirteen cyclists had at least one of the following: orthostatic
      hypotension, rigors, nausea, vomiting, diarrhea, or syncope. Only 2/26 case
      controls had any of these symptoms. Data were collected on vital signs,
      hemoglobin, sodium, creatine kinase, creatinine, and uric acid. Endotoxin titer
      was determined by chromogenic assay; tumor necrosis factor alpha (TNF-alpha)
      titer was determined by ELISA. One ill cyclist had an endotoxin level of 330
      pg.ml-1, one control had an endotoxin level of 150 pg.ml-1, but endotoxin level
      was < or = 64 pg.ml-1 in all others. Comparison of pre- and post-ride data showed
      that controls increased creatine kinase activity (154 +/- 34 vs 561 +/- 191
      IU.dl, P < 0.05), creatinine concentration (1.5 +/- 0.0 vs 1.6 +/- 0.0 mg.dl-1, P
      < 0.05), and uric acid concentration (5.4 +/- 0.3 vs 6.3 +/- 0.3 mg.dl-1, P <
      0.05). Ill cyclists had lower serum sodium than post-ride controls (138 +/- 2 vs
      142 +/- 0.6 mEq.l-1, P < 0.05), but there were no differences between groups in
      CK, creatinine, or uric acid. These findings suggest that endotoxemia may
      complicate, but does not cause mild post-exertional illness in cyclists.

PMID- 8531622
TI  - Fat-free mass is maintained in women following a moderate diet and exercise
      program.
AB  - Weight-loss programs usually result in fat-free mass (FFM) loss along with body
      fat (BF) loss. This study examined which combination of diet + exercise would
      maintain FFM. Forty-four overweight, inactive women completed 20 wk of a
      randomized intervention: control (C, N = 6), diet only (D, N = 10), diet +
      cycling (DC, N = 8), diet + resistance training (DR, N = 11), or diet +
      resistance training + cycling (DRC, N = 9) group. FFM and %BF were determined
      from hydrostatic weighting. Exercise sessions were attended 3 d.wk-1, with a mean
      duration of 30 min per session. Caloric intake was reduced 628 kcal.d-1 (+/- 59).
      Chi squares and ANOVA showed no baseline differences between groups for
      socioeconomic status, age, body composition, aerobic capacity, or strength. One
      way ANOVA of change with Student-Newman Keul multiple range post-hoc tests (P <
      0.05) were used to analyze pre to post differences for %BF, body mass (BM), FFM,
      VO2max, and strength. D, DC, DR, and DRC lost significant BM (-3.7 to -5.4 kg) in
      comparison with C (+ 1.5 kg). All groups maintained FFM but only DRC
      significantly lowered %BF (-4.7%) in comparison with C. DRC and DC significantly
      increased VO2max. Strength 1RM (triceps extension, arm curl, leg extension, chest
      press) increased significantly for both DR and DRC. Results suggest that moderate
      levels of caloric restriction, aerobic cycle exercise, and/or resistance training
      are equally effective in maintaining FFM while encouraging body mass loss.

PMID- 8531623
TI  - Cardiovascular effects of androgenic-anabolic steroids.
AB  - Evidence has accumulated over the pst several years which associates androgenic
      anabolic steroid (AAS) use with sudden cardiac death, myocardial infarction,
      altered serum lipoproteins, and cardiac hypertrophy in humans who habitually use
      these drugs. Even though some experimental data obtained from animals correlate
      well with the human findings, the adverse cardiovascular effects of AAS use are
      poorly understood. The evidence presented in this review suggests that there are
      at least four hypothetical models of AAS-induced adverse cardiovascular effects:
      1) an atherogenic model involving the effects of AAS on lipoprotein
      concentrations; 2) a thrombosis model involving the effects of AAS on clotting
      factors and platelets; 3) a vasospasm model involving the effects of AAS on the
      vascular nitric oxide system; and 4) a direct myocardial injury model involving
      the effects of AAS on individual myocardial cells. Future studies should be
      directed at determining the exact mechanisms responsible for AAS-induced adverse
      cardiovascular effects, at determining the relative contribution of each of these
      models, and at identifying other possible contributing factors such as metabolism
      of these steroids and the effects of potential metabolites on various target
      organs.

PMID- 8531624
TI  - Muscle damage following repeated bouts of high force eccentric exercise.
AB  - This study was designed to test the hypothesis that performing repeated bouts of
      eccentric exercise when muscles were not recovered from previous exercise would
      exacerbate muscle damage. Twelve nonweight-trained males (21.7 +/- 2.4 yr)
      performed three sets of 10 eccentric actions of the elbow flexors (ECC) using a
      dumbbell that was set at 80% of the preexercise maximal isometric force level.
      This same exercise was repeated 3 and 6 d after the first exercise. Maximal
      isometric force, relaxed and flexed elbow joint angle, muscle soreness, plasma
      creatine kinase, and glutamic-oxaloacetic transaminase activities were assessed.
      Ultrasound images were taken from the upper arm. These measures (except soreness)
      were assessed immediately before and after each eccentric exercise bout (ECC1,
      ECC2, and ECC3) and 3 d after ECC3. Soreness was assessed prior to ECC1 and once
      a day for 9 d thereafter. All criterion measures changed significantly (P < 0.01)
      after ECC1. ECC2 and ECC3 performed 3 and 6 d after ECC1 did not exacerbate
      damage and did not appear to slow the recovery rate. Increased echointensity in
      ultrasound images was demonstrated following ECC1, but no indication of increased
      damage was found after ECC2 and ECC3. Strenuous exercise performed with "damaged"
      muscles did not exacerbate damage or affect the repair process.

PMID- 8531625
TI  - Diabetic nephropathy in an aerobically trained rat model of diabetes.
AB  - The purpose of this study was to determine the effects of aerobic training on
      indices of glycemic control, blood pressure, serum lipids, and diabetic
      nephropathy (DN) in an animal model of insulin deficient diabetes mellitus.
      Thirty-four male Sprague-Dawley rats made diabetic with streptozocin were
      randomly assigned to a trained group or a sedentary group. Fifteen sedentary
      nondiabetic rats served as a control group. The animals were trained on a
      treadmill at 18 m.min-1, 8 degrees incline for 120 min.d-1, 5 d.wk-1. Blood and
      24 h urine collections were obtained at various intervals throughout the study.
      At 21 wk of age systolic blood pressure was measured and kidney tissue was
      obtained for light and electron microscopy. Analysis of variance was used to
      detect differences among the groups (P < or = 0.05). The diabetes produced in
      this investigation resulted in hyperglycemia, increased urine albumin and total
      protein excretion, elevated systolic blood pressure, increased fractional volume
      of the mesangium, and widening of the glomerular basement membrane in the
      sedentary-diabetic animals. Aerobic training significantly reduced the increase
      in fractional volume of the mesangium and fructosamine. Most importantly, aerobic
      training did not augment the renal damage seen in DN.

PMID- 8531626
TI  - No effect of glycogen level on glycogen metabolism during high intensity
      exercise.
AB  - This study examined the effect of glycogen supercompensation on glycogen
      breakdown, muscle and blood lactate accumulation, blood-pH, and performance
      during short-term high-intensity exercise. Young healthy volunteers performed two
      supramaximal (125% of VO2max) exercise tests on a bicycle ergometer, either for 1
      min 45 s (protocol 1; N = 18) or to exhaustion (protocol 2; N = 14). The exercise
      tests were preceded by either 5 d on a controlled normal (N) diet, or by 2 d of
      glycogen-depleting exercise accompanied by the normal diet followed by 3 d on a
      carbohydrate-rich (CHR) diet. In protocol 1, preexercise muscle glycogen
      concentrations were 364 +/- 23 and 568 +/- 35 mumol.g-1 d.w. in the N and CHR
      condition, respectively (P < 0.05). During the exertion, glycogen concentration
      in the M. quadriceps decreased to the same extent in both groups. Accordingly,
      the exercise-induced increases in muscle and blood-lactate, and the fall in blood
      pH were similar during N and CHR. In protocol 2, time to exhaustion was identical
      for N and CHR. It is concluded that during short-term intense exercise during
      which muscle glycogen availability exceeds glycogen demand, rate of glycogen
      breakdown, lactate accumulation, and performance are regulated irrespective of
      the preexercise muscle glycogen level.

PMID- 8531627
TI  - Gas exchange kinetics during functional electrical stimulation in subjects with
      spinal cord injury.
AB  - We examined the kinetics of VO2, VCO2, and VE following the onset of unloaded leg
      cycling, and in recovery, in six patients with spinal cord injury (SCI). Exercise
      was produced by functional electrical stimulation (FES) of the quadriceps,
      hamstrings, and gluteal muscles. End-exercise VO2 (1.03 +/- 0.16 l.min-1), VCO2
      (1.20 +/- 0.22 l.min-1) and VE (41 +/- 10 l.min-1) were elevated compared to
      values typically seen in healthy ambulatory subjects performing similar unloaded
      cycling. Mean response times for the on transients (MRTon) were both long and
      variable across subjects for VO2 (165 +/- 62 s), VCO2 (173 +/- 58 s), and VE (202
      +/- 61 s). Recovery kinetics showed much less intersubject variability, and for
      five of six subjects were faster than the equivalent exercise MRT for all three
      variables (MRToff for VO2 of 103 +/- 28 s, VCO2 136 +/- 20 s, and VE 144 +/- 34
      s), but P > 0.05 for all three. Size of the O2 deficit (1.96 +/- 0.90 l) and end
      exercise lactate (7.05 +/- 1.65 mmol.l-1) were similar to values reported for
      healthy sedentary subjects performing maximal voluntary exercise, but the end
      exercise heart rate (102 +/- 16 bpm) was lower than expected for this intensity
      of exercise. In conclusion, FES-induced unloaded cycling leads to exaggerated
      responses of pulmonary gas exchange and long time constants in patients with SCI.
      The delayed kinetics may be due in part to a blunted increase in heart rate in
      addition to severe deconditioning.

PMID- 8531628
TI  - Criteria for maximal oxygen uptake: review and commentary.
AB  - Historically, the achievement of maximal oxygen uptake (VO2max) has been based on
      objective criteria such as a leveling off of oxygen uptake with an increase in
      work rate, high levels of lactic acid in the blood in the minutes following the
      exercise test, elevated respiratory exchange ratio, and achievement of some
      percentage of an age-adjusted estimate of maximal heart rate. These criteria are
      reviewed relative to their history, the degree to which they have been achieved
      in published research, and how investigators and reviewers follow them in current
      practice. The majority of the criteria were based on discontinuous protocols,
      often carried out over several days. Questions are raised about the applicability
      of these criteria to modern continuous graded exercise test protocols, and our
      lack of consistency in the terminology we use relative to the measurement of
      maximal oxygen uptake.

PMID- 8531629
TI  - Physiological characteristics and performance of top U.S. biathletes.
AB  - Success in biathlon involves skiing fast and shooting accurately. The purpose of
      this study was to determine whether physiological laboratory test results relate
      to success in biathlon. Tests included treadmill run and double-pole lactate
      profile and VO2peak tests, and a double-pole peak power test (UBP). 1993 National
      Points Rank (NR), racing ski time (ST), and shooting percentage (SP) from 1993
      World Team Trials and laboratory test results (1993; N = 11 males, 10 females)
      were examined. Of athletes tested, six males and six females were top 10 U.S.
      ranked. Significance was identified between NR and ST (males, r = -0.88; females,
      r = -0.91). NR and SP were related for females (r = 0.75). Maximum run time
      during the VO2peak test was the only parameter related to NR (r = 0.72) or ST (r
      = -0.80) for males. Significance was identified for an uphill 1 km on snow double
      pole time trial to NR (r = -0.84) and SP (r = -0.79) (subgroup; N = 8 males). For
      females, NR was related to running VO2peak (r = 0.81) and UBP (r = 0.95). Double
      pole and running VO2peak were related to SP for women. This study suggests that
      SP is more important to NR for females than for males, and gender-specific tests
      might better predict success in elite biathlon skiers.

PMID- 8531630
TI  - Energy expenditure in adolescents during low intensity, leisure activities.
AB  - We sought to determine how a stationary activity such as playing a stringed
      instrument may affect energy expenditure (EE) in adolescents. Using automated
      indirect calorimetry, we measured EE in eight adolescents (1 male, 7 females,
      14.2 +/- 2.1 yr) while they each performed the following activities: watching
      television (TV) (60 min), playing a stringed instrument (60 min), and walking at
      40% of peak oxygen uptake (43 min). Measurements were made during three, 6- to 7
      min steady state periods of each activity. EE (mean +/- SD) was lower during TV
      (1.0 +/- 0.2 kcal.min-1) and instrument playing (1.4 +/- 0.2 kcal.min-1) than
      during walking (3.4 +/- 0.4 kcal.min-1) (P < 0.05). EE during instrument playing
      was 41% greater than during television viewing (P < 0.05). We conclude that
      relatively sedentary activities such as playing a stringed instrument can elevate
      EE. Conceivably, other stationary, leisure activities performed by adolescents
      may increase EE and have substantial, cumulative effects on long-term energy
      balance and fat accretion.

PMID- 8531631
TI  - Evaluation of the ACSM submaximal ergometer test for estimating VO2max.
AB  - The purpose of this investigation was to assess the reliability and validity of
      maximal oxygen uptake estimates (ESTmax) from the ACSM submaximal cycle ergometer
      test. Subjects included 15 men and 15 women aged 21-54 yr who performed two
      submaximal tests and one maximal cycle ergometer test to determine maximal oxygen
      uptake (VO2max). During the submaximal tests, heart rates (HR) were recorded from
      a radio telemetry monitor. ESTmax was predicted for both submaximal trials by
      extrapolating HR to an age-predicted maximal HR. Correlation coefficient and
      standard error of measure (SEmeas) for ESTmax between submaximal trials were r =
      0.863 and SEmeas = 0.40 l.min-1, while a t-test revealed no significant
      difference between trials. Although trial means were not significantly different,
      large variation in individual cases was evident by the high SEmeas (0.40 l.min-1)
      and by a large SEmeas expressed as a percentage of the mean (13%). The mean of
      the two ESTmax significantly overestimated measured VO2max with percent error,
      total error, and mean error equal to 25.7%, 0.89 l.min-1, and 0.63 l.min-1,
      respectively. The standard error of estimate expressed as a percentage of the
      mean was equal to 16% and 15% for both ESTmax. In summary, the ACSM protocol
      failed to be reliable as represented by the large differences found between
      submaximal trials. Furthermore, the protocol significantly overestimates VO2max
      and should not be used when an accurate assessment of VO2max is required.

PMID- 8531632
TI  - Validity of skinfold equations for estimating body density in youth wrestlers.
AB  - The present investigation examined the validity of 16 skinfold equations for
      predicting body density (BD) in youth wrestlers (mean age +/- SD = 11.0 +/- 1.3
      yr) by comparing the values to those obtained from underwater weighing. Forty
      eight members of youth wrestling clubs (mean BD +/- SD = 1.0634 +/- 0.0125 g.cm
      3) volunteered to serve as subjects. The statistical analyses included
      examination of the constant error (CE), standard error of estimate (SEE),
      correlation coefficient (r), and total error (TE). The results of this
      investigation indicated that all of the equations resulted in TE values that were
      > or = 0.0106 g.cm-3 (range = 0.0106-0.0229 g.cm-3) which corresponded to > or =
      4.9% body fat. The TE values were too large to provide accurate estimates of body
      composition in the present sample of youth wrestlers. Future studies should use
      the CE values from the present investigation to adjust the intercepts of the
      skinfold equations in the present study and cross-validate the modified equations
      on young male athletes.

PMID- 8531633
TI  - The stability of children's physical activity as measured by accelerometry and
      self-report.
AB  - The Computer Science Application (CSA) accelerometer uses integrated circuitry
      and memory to provide a continuous recording of minute-by-minute movement counts.
      It has been previously validated as an objective monitor of children's physical
      activity in field and laboratory settings. Our purpose was to derive
      accelerometry summary variables reflective of different physical activity
      intensity levels, evaluate the stability of these summary variables, and define
      the number of days needed to adequately measure usual physical activity. A
      secondary study purpose was to compare three self-report questionnaires to
      accelerometry. Thirty children (7-15 yr) wore accelerometers for 12 h.d-1 for 6
      d. Daily summary variables of average movement count (total physical activity)
      and daily frequency of sedentary through vigorous activity were constructed.
      Intraclass correlation coefficients (R) and 95% confidence intervals (CI) were
      used to analyze the data. Accelerometry stability using 1 monitored day to
      represent usual physical activity was R = 0.42-0.47. When 6 d were used,
      stability increased to R = 0.81-0.84. Acceptable intraclass correlations and CI
      were achieved with 4 d of monitoring (R = 0.75-0.78, CI = 0.60-0.88). The self
      report questionnaires were poorly to moderately correlated to accelerometry
      variables (r = -0.03-0.51). Data indicate that in field settings: 1)
      accelerometry can be used to assess the intensity of children's activity and 2) 4
      or more days of activity monitoring are needed to achieve satisfactory
      reliability.

PMID- 8531634
TI  - Evaluation of the Cosmed K2 telemetry system during exercise at moderate
      altitude.
AB  - The aim of this study was to test the linearity, precision, and accuracy of the
      measurements made by the K2 system at sea level (SL) and moderate altitude (MA)
      (barometric pressure = 591.5 +/- 0.5 mm Hg). To minimize the day-to-day
      biovariability, a testing protocol based on repeated-alternated measures was used
      at rest and during three levels of submaximal exercice lasting 12 min each, at
      25%, 50%, 75% of the peak workload. The measurements of the respiratory
      parameters were compared with those obtained with a metabolic measurement cart.
      The results reported in this study show that the K2 system was an accurate and
      consistent system for oxygen uptake (VO2) measurements at SL. The K2 system was
      consistent at MA; however, the K2 system significantly overestimated and
      underestimated the VO2 computations at rest and 25% of the peak workload,
      respectively. The calculation of VO2 using the K2 system which assumes that RER =
      1.00 had specific effects for the calculation of oxygen uptake. The measurements
      of FEO2 selectively differed from those obtained with the metabolic measurement
      cart at MA. Therefore, we concluded that the K2 system was an accurate system for
      VO2 measurements during submaximal exercices (50%-75% of the peak workload) under
      laboratory conditions at MA (up to 2,000 m).

PMID- 8531635
TI  - A chronically instrumented rat model to assess the altered baroreflex due to
      exercise.
AB  - We developed a conscious, chronically instrumented, exercise-trained rat model
      and examined the time course of the training-induced alteration of baroreflex
      function in response to hypertensive conditions. Exercise-trained (ET) animals
      ran at 18 m.min-1, 15% grade, for 60 min.d-1, 5 d.wk-1 for 5 wk. Baroreflex tests
      were conducted on day 6 each week. Regression line slopes relating the change in
      mean arterial pressure (delta MAP) to the change in heart rate (delta HR) were
      used to assess baroreflex sensitivity. Intravenous injections of phenylephrine
      were used to create hypertensive conditions. Compared with the C group, slopes of
      ET animals were reduced (from 2.1 to 1.2 bpm.mm Hg-1, P < 0.05) as early as week
      3 of training in response to increasing doses of PE, and reached 0.8 bpm.mm Hg-1
      by the end of training. The reflex bradycardiac response (delta HR) to PE was
      reduced (P < 0.05) depending on the dose of PE and the duration of training: in
      micrograms PE.kg-1 body weight, 5 (71% +/- 6% of control at week 2), 3 (70% +/-
      7% of control at week 3, and 1 (61% +/- 10% of control at week 4). The pressor
      (delta MAP) to PE remained constant throughout training. Thus, using a
      chronically instrumented rat model that maintains the ability to run, we observed
      that the ability of the arterial baroreflex to produce bradycardia during pressor
      events was substantially reduced following as few as 2 wk of training.

PMID- 8531636
TI  - Microsurgery in Russia: past and present.

PMID- 8531637
TI  - Resurfacing of the damaged hand by the prefabricated free flap including serratus
      fascia: a case report.

PMID- 8531638
TI  - Plea to save the great toe in total thumb reconstruction.
AB  - Thumb reconstruction remains a controversial field. In young, well-motivated
      patients, in the absence of avulsion injuries, toe to hand transfer is an
      accepted procedure. With refinement, it is possible to avoid sacrifice of the
      great toe and in many cases avoid resorting to a second toe which is functionally
      and cosmetically insufficient. Custom-made reconstruction allows us both to save
      the donor great toe and to improve function and cosmesis of the donor site. Three
      basic techniques are reviewed: the modified wrap-around, bipolar lengthening, and
      twisted two-toes techniques.

PMID- 8531639
TI  - Histomorphometric examinations of free revascularised iliac crest bone after
      transplantation for mandibular reconstruction.
AB  - At the present time the vascularised bone graft is the best procedure for
      reconstruction of mandibular defects in poor recipient tissues. We obtained 23
      drill biopsies from different regions of vascularised bone transplants during the
      removal of the osteosynthesis plates from 14 patients who had poor recipient
      tissues. For comparison, we took five biopsies from the native iliac crest and
      eight biopsies from six patients with avascular bone transfer into unimpaired
      surrounding tissues. Microradiographs of the bone preparations were used for a
      computerised semi-automatic morphometric analysis. We evaluated the volumetric
      density (VV, %) and the mean trabecular diameter (D-TRAB, micron). In the central
      regions, the revascularised transplants decreased in volumetric density and in
      mean trabecular diameter. Compared with the average values of iliac crest bone,
      the avascular grafts increased in both parameters. The revascularised grafts
      showed significantly lower volumetric density and significantly lower mean
      trabecular diameters in the central regions than in the regions near to the
      mandibular stump. The avascular grafts actually showed the reverse effect. The
      results are discussed with particular reference to the quality of the recipient
      tissues, to the maintenance of graft viability, to functional stress, and to the
      design of the transplant.

PMID- 8531640
TI  - The free vascularised fibular transfer as a definitive treatment in femoral
      septic non-unions.
AB  - Free vascularised bone transfer (fibula, iliac crest, or rib) is an accepted
      method of bone grafting in malignant and non-union bone surgery. The vascular
      microanastomoses have transformed the bone healing by creeping substitution seen
      after non-vascularised grafting (a long and often insufficient process) into
      normal healing of the fracture site. The presence of its own vascular support
      allows bone healing in such compromised circumstances as sclerosis and infection.
      We present the clinical history of five patients with septic femoral non-unions,
      in which only the final vascular fibular graft provided an acceptable outcome.
      Discussion about the indication and timing of this microsurgical salvage
      procedure is still controversial.

PMID- 8531641
TI  - Reinnervation and neovascularisation in prefabricated free muscle flaps.
AB  - In this study, immediate muscle reinnervation in flap prefabrication was
      investigated and compared with those flaps which were reinnervated after
      prefabrication. Using the flow-through wrap-around technique for
      neovascularisation, denervated external abdominal oblique random muscle flaps in
      Lewis rats were either immediately reinnervated by implantation of the epigastric
      nerve or reinnervated late after free transfer, following the prefabrication
      period of 15 days. Half of the flaps from each group were microsurgically
      transferred to isogeneic rats. Thirty days later, the flaps were harvested, and
      neovascularisation and reinnervation were studied with microangiography and
      immunohistochemistry using antibodies to protein gene peptide (PGP) 9.5,
      calcitonin gene-related peptide (CGRP), and von Willebrand factor (vWF).
      Microangiography and quantification of the vWF-stained vessels in the flaps
      confirmed increased neovascularisation over a longer time course. Reinnervation
      was found to have no influence over neovascularisation. Nerve sprouting was
      present 15 days after nerve implantation to the muscle and became widespread by
      30 days. CGRP immunoreactivity, which is thought to have some role in trophic and
      regulatory processes, was observed only after 30 days of reinnervation.
      Regardless of the timing and extent of reinnervation, a considerable amount of
      muscle atrophy was observed in the flaps.

PMID- 8531642
TI  - Free flap failures.
AB  - A retrospective analysis of 75 consecutive free flap patients, operated on during
      1989-1990, was performed to find out more about factors associated with free flap
      failure or immediate vascular complications. The overall failure rate was 9.3%
      (7/75) and the immediate vascular complication rate 22.7% (17/75). Sixteen
      patients required explorative surgery during the first postoperative day. The
      results were statistically analysed to find factors promoting either failure or
      vascular complications. Pre-operative infection of the recipient site or
      prolonged operation time correlated with flap failure. The use of a vein graft or
      long per-operative ischaemia correlated with immediate vascular complications. It
      is interesting that many factors often blamed for failure (age, body mass,
      history of cardiovascular disease, smoking, or previous irradiation of the
      recipient site) were not significant in this study.

PMID- 8531643
TI  - Vascular complications after free tissue transfer.
AB  - Between 1981 and 1992, 631 cases of free tissue transfer were operated on at our
      clinic. Of these cases, 489 were reviewed for vascular complications. The aim of
      the study was to evaluate retrospectively possible correlations between
      complications and operative faults. Vascular complications occurred in 16%. By
      immediate operative revision 50% of the cases with a vascular complication could
      be salvaged. In general, earlier diagnosis and treatment of vascular
      complications after free tissue transfer prompted a higher success rate of the
      surgical revision.

PMID- 8531644
TI  - Neo-endothelialisation of PTFE microvascular grafts: a five-year experience.
AB  - This paper presents the results of a 5-year experience of the implantation of 1
      mm diameter polytetrafluoroethylene (PTFE) prosthesis in rodents. By evaluating
      the implanted grafts at different intervals, the process of neo-endothelial
      healing can be divided into six phases: Platelet Aggregation Phase (Stage I);
      Fibrin Network Phase (Stage II); Bridging Phase (Stage III); Progression Phase
      (Stage IV-A); Transmural Migration Phase (Stage IV-B) (only in optimal grafts,
      with thin wall and long fibril length); Intimal Closure Phase (Stage V); and
      Endothelial Thromboresistance Phase (Stage VI). Grafts with 60 or 90 microns
      fibril length offer enough "anchoring space" for the ingrowth of neo-endothelium
      and they act as a framework for the neo-endothelial invasion. Furthermore, this
      type of material allows intramural migration and penetration of cellular
      elements. In particular, a network of capillaries traversing the graft wall and
      opening eventually on the luminal surface can provide multiple sources of neo
      endothelium, contributing to the development of the inner neo-endothelial lining.
      Scanning electron microscopy can favourably assist in the evaluation of different
      types of PTFE grafts, with regard to their fibril length, diameter, and wall
      thickness.

PMID- 8531645
TI  - Clinical use of microvascular PTFE grafts.
AB  - This paper reports on the first clinical case where a polytetrafluoroethylene
      (PTFE) graft of less than 3 mm in diameter was implanted in the arterial system
      of a patient to bridge a vascular defect. A 1.5 cm long, 1.5 mm diameter
      prosthesis was interposed in the superficial palmar arch of a man who sustained a
      laceration of the palm of his dominant hand. The graft was implanted by means of
      the 3M Precise Microvascular Anastomotic System on one end, and by conventional
      microsurgical technique on the other end. There were no postoperative
      complications. The patient resumed his pre-injury activities 9 weeks after
      trauma. Serial Doppler ultrasound examinations showed normal blood flow and
      complete patency of the graft. An angiogram performed 12 weeks postoperatively
      confirmed the patency of the prosthesis. Twelve months post-operatively the
      patient is free from complications. The use of small diameter PTFE prostheses may
      be considered when planning grafting procedures for microvascular defects.

PMID- 8531646
TI  - The combined meeting of the Group pour l'Avancement de Microchirurgie and the
      British Microsurgical Society. Lille, France and Ashford, United Kingdom.
      Abstracts.

PMID- 8531647
TI  - Proceedings of the IVth International Symposium on Schistosomiasis and the IV
      National Meeting on Schistosomiasis. Rio de Janeiro, Brazil, 29 November to 3
      December 1993.

PMID- 8531648
TI  - Ultrasonography in schistosomiasis in Africa.
AB  - Approximately 50 publications have become available in the international
      literature on ultrasonography in schistosomiasis in Africa. Geographically these
      cover Congo, Egypt, Kenya, Mali, Mauritius, Niger, Senegal, Sudan, Tanzania and
      East African Islands as well as Zimbabwe. Further studies are ongoing in many
      countries, such as Burundi, Ghana, Madagaskar and Uganda. It was shown that
      ultrasonography is useful in the detection of morbidity induced by
      schistosomiasis on an individual basis and on the community level. There is
      indication for varying morbidity patterns in different African foci. Post
      treatment monitoring has provided evidence for reversibility of pathological
      lesions induced by Schistosoma (S.) haematobium and S. mansoni, even though
      evidence for reversibility of periportal fibrosis in adults is not yet
      satisfactorily substantiated. A standardized set of criteria for
      ultrasonographical observations has been worked out and is presently in the
      process of being refined. It is thus hoped that standardization will contribute
      to render studies in different endemic settings comparable on a global basis.

PMID- 8531649
TI  - The use and limitations of ultrasonography in the diagnosis of liver morbidity
      attributable to Schistosoma mansoni infection in community-based surveys.
AB  - The objective of this population-based study was to estimate the liver morbidity
      attributable to Schistosoma mansoni infection by ultrasonography adopting the
      proposed standard protocols of the Cairo Meeting on Ultrasonography, 1991. We
      examined 2384 individuals representing 20% of the households of the rural
      population of the Ismailia Governorate, East of Delta, Egypt. Prevalence of S.
      mansoni and S. haematobium infections were 40.3% and 1.7% respectively. Portal
      tract thickening (PTT) grade 1, 2 and 3 considered diagnostic of schistosomal
      liver morbidity was detected in 35.1%, 1.3 and 0.2 individuals respectively.
      Generally, ultrasonographically-detected pathological changes increased with age,
      but correlated with intensity of infection only in age group 20-59 years.
      Comparing individuals with and without S. mansoni infections in an endemic and a
      non-endemic community indicated no significant difference between the former and
      the latter in either case. IN CONCLUSION: ultrasonography had a limited value in
      estimating schistosomal liver morbidity in our population-based study where early
      grades of liver morbidly were prevalent. The criteria of diagnosing grade I
      portal fibrosis need to be revised as well as the staging system proposed by the
      Cairo Meeting on ultrasonography in schistosomiasis.

PMID- 8531650
TI  - Determination and control of schistosomiasis.
AB  - The subject of this conference reflects the scientific community's interest in
      seeking to understand the complex causal web whose various social, economic, and
      biological components interact in the production and reproduction of
      schistosomiasis and its control in relation to community participation. From the
      onset, the author stresses the impossibility of dealing separately with community
      participation, as if social components were just one more "weapon" in the arsenal
      for schistosomiasis control. This study begins with a brief historical review of
      the 71 years of control activities with this endemic disease, stressing the
      enormous efforts and huge expenditures in this field vis-a-vis the limited
      results, despite the extraordinary technological development of specific,
      classical control inputs such as new treatment drugs and molluscicides. The
      article then discusses the various strategies used in control programs,
      emphasizing ideological consistencies and contradictions. Interactions at the
      macro and micro levels are discussed, as are the determinants and risk factors
      involved in producing the disease's endemicity. Unequal occupation of space
      leaves the segregated portion of the population exposed to extremely favorable
      conditions for transmission of the disease. This raises the issue of how to
      control an endemic disease which is so closely linked to the way of life imposed
      on the population. The study challenges the classical control model and suggests
      an alternative model now undergoing medium-term investigation in the States of
      Espirito Santo, and Pernambuco, Brazil. The author concludes that we do not need
      new strategies, but a new control model, contrary to the prevailing classical
      model in both concept and practice. From the conceptual point of view, the new
      model mentioned above is different from others in that schistosomiasis control is
      seen from a social perspective stressing the population's accumulated knowledge
      in addition to the building of shared knowledge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531651
TI  - Treatment of schistosomiasis: gathering stones together.

PMID- 8531652
TI  - Molluscicide control of snail vectors of schistosomiasis.
AB  - A review of the methodology recommended by the World Health Organization for the
      use of molluscicides for the control of snail vectors of schistosomiasis is
      presented. Discussion of the principle molluscicides used, their advantages and
      disadvantages, the techniques and equipment required for their application and
      evaluation of effect as well as the biological control of snails is included.

PMID- 8531653
TI  - Extramedullary hematopoiesis in murine schistosomiasis mansoni.
AB  - During Schistosoma mansoni infection, there is morphological evidence of
      involvement of various hematopoietic growth factors, which cause eosinophil,
      neutrophil, megakaryocytic and erythroid extramedullary foci in the liver, lymph
      nodes and omental and mesenteric milky spots. While the eosinophil metaplasia in
      the periphery of hepatic granulomas roughly reproduced the intensity of the
      medullary eosinopoiesis, the neutrophil metaplasia, on the contrary, was more
      intense during the period of neutrophil depression in the bone marrow. This fact
      suggests that extramedullary hematopoietic foci are locally regulated, and
      amplify and/or compensate the systemic hematopoietic response during the
      infection.

PMID- 8531654
TI  - Molecular aspects of Schistosoma mansoni female maturation.
AB  - Incubation of total protein extracts of Schistosoma mansoni with 3H 17-beta
      estradiol and 20-hydroxyecdysone, revealed steroid binding proteins in both, male
      and female worms. The interaction of nuclear proteins with restriction fragments
      of the gender and stage-specific gene F-10 was investigated using the "Band
      Shift" technique. Distinct male and female nuclear proteins bound to the
      fragments of this gene. Among the nuclear proteins, only those rich in cysteine
      residues bound to DNA. In vitro incubation of live worms with the estrogen
      antagonist Tamoxifen, altered the pattern of the DNA binding proteins, producing
      in females, a band profile similar to that obtained with male worm protein
      extracts. When Tamoxifen was injected into schistosome infected mice, the eggs
      produced by females presented an abnormal morphology, compatible with non-viable
      eggs. These results suggest that the regulation of transcription of the F-10 gene
      might involve steroid receptors.

PMID- 8531655
TI  - Schistosoma mansoni: control of female fertility by the male.
AB  - We have established an in vitro culture system for adult schistosomes that allows
      monitoring gene expression for up to more than ten days. Comparing female worms
      that are paired with those that have been separated, we find distinct
      differences, clearly documenting an influence of the male in female gene
      expression. In perfect coincidence with classical observations that were based on
      histological techniques, we find that the male particularly regulates gene
      expression in those tissues that are characterized by cell proliferation, e.g.
      the vitellaria. From these results, we hypothesize that the key target for the
      inductive signal that is transferred from the male to the female during pairing
      is the activation of a growth factor that stimulates mitotic proliferation.

PMID- 8531656
TI  - Effect of Niclosamide (Bayluscide WP 70), Anacardium occidentale hexane extract
      and Euphorbia splendens latex on behavior of Biomphalaria glabrata (Say, 1818),
      under laboratory conditions.
AB  - The repellent effect of the molluscicides Niclosamide (Bayluscide WP 70),
      Anacardium occidentale and the latex of Euphorbia splendens on Biomphalaria
      glabrata was observed through the investigation of the occurrence of escape
      behavior among molluscs that were exposed to dosages lower than the LD 50. The
      total number of individuals out of water among the surviving snails in the
      control group provided a "Natural Escape Index". The comparison between this
      total and the total number of surviving snails in each group exposed to the
      different dosages of the molluscicides after 24 hr provided the "Molluscicide
      Escape Index" and the detection of a "Repellency Range" to these snails. The
      escape indexes for Niclosamide, A. occidentale and E. splendens were 10%, 6.22%
      and 6.44% respectively. Repellency occurred at the following concentration
      ranges: 0.01, 0.02 and 0.03 ppm Bayluscide, 0.1, 0.2 and 0.3 ppm A. occidentale
      and 0.05, 0.10, 0.15 and 0.20 ppm E. splendens. The Natural Escape Index obtained
      in the control group was zero.

PMID- 8531657
TI  - The snail hosts of schistosomiasis: some evolutionary and ecological perspectives
      in relation to control.
AB  - Despite opportunities for radiation provided by spatio-temporal isolation, the
      basic morphological plan of pulmonate snails has remained conservative. In
      consequence of the resulting dearth of morphological characters and their
      plasticity, there is a case for using biochemical characters such as exogenous
      chemicals released by the snails (e.g. amino acids) and their chemoreception
      niche as taxonomic aids to classify snails of medical importance. As these same
      chemicals are used by snails to distinguish conspecifics they could also be used
      as "environmental antibodies" in controlled release formulations (CRF's) designed
      to remove target snails in a specific, cost-effective and ecologically acceptable
      manner. The snails, surface-living bacteria, algae and macrophytic plants are
      considered as co-evolved, interactive modular systems with strong mutualistic
      elements. Recently, anthropogenic perturbations such as deforestation, and
      damming of flowing waters, have benefited these modules whereas others such as
      river canalization, acid deposition, accumulation of pesticide residues and
      eutrophication have harmed them. Research is needed to elucidate the factors
      which limit the growth of snails in primitive habitats, uninfluenced by man, as
      well as in those subject to harmful anthropogenic factors. The understanding thus
      gained could be applied to develop cost-effective primary health care strategies
      to reduce or prevent transmission of schistosomiasis and other water related
      diseases.

PMID- 8531658
TI  - The geographic understanding of snail borne disease in endemic areas using
      satellite surveillance.

PMID- 8531659
TI  - DNA polymorphism of schistosomes and their snail hosts.
AB  - Analysis of the genomes of schistosomes and one of their intermediate hosts,
      Biomphalaria glabrata, using Random Amplified Polymorphic DNA (RAPD) demonstrated
      that intraspecific genetic polymorphism in the parasite is limited but in the
      snail is highly pronounced. This suggests an important role for the snail in the
      determination of the epidemiology of the disease. In addition to their
      intraspecific stability, schistosome derived RAPDs exhibit a high level of
      interspecific polymorphism and are thus ideal for the construction of
      phylogenetic trees. For the detection of intraspecific polymorphisms extensive
      variation in the mitochondrial DNA is being exploited for the development of a
      PCR based test for Schistosoma mansoni. Gene level polymorphisms are being
      analyzed by Low Stringency Single Specific Primer PCR.

PMID- 8531660
TI  - Sequencing and identification of expressed Schistosoma mansoni genes by random
      selection of cDNA clones from a directional library.
AB  - We have initiated a gene discovery program in Schistosoma mansoni based on the
      technique of Expressed Sequence Tags (ESTs), i.e. partial sequences of cDNAs
      obtained from single passes in automatic DNA sequences. ESTs can be used to
      identify genes on the basis of their homology with sequences from other species
      deposited in DNA or protein databases. Transcripts with sequences without matches
      in the databases may represent novel parasite-specific genes. This approach has
      shown to be very efficient and in less than two years a broad range of novel
      genes has already been ascertained, more than doubling the number of known S.
      mansoni genes.

PMID- 8531661
TI  - Opportunities and constraints in schistosomiasis vaccine development: infection
      characteristics and industry realities.
AB  - The notes provided in this article relate to two components of the development of
      vaccines against schistosomiasis: (1) The characteristics of schistosome
      infections (eg. features of the schistosome life cycle), and the parasite itself,
      that have implications for vaccination strategies; (2) The characteristics of the
      biopharmaceutical industry that have implications for product development. As
      will be seen, these two topic areas are not vastly disparate.

PMID- 8531662
TI  - Schistosomiasis vaccine development: approaches and prospects.
AB  - Mounting evidence for acquired immunity to schistosomiasis in humans supports the
      case for immunological intervention. On the other hand, rapid reinfection poses a
      threat to younger age groups due to the slow maturation of natural resistance.
      However, rational approaches, based on advances in immunology and molecular
      biology, have substantially increased the odds of producing an effective vaccine.
      Since the parasite cannot replicate in the human host and serious morbidity
      generally occurs only after a relatively long period of heavy worm burden,
      complete protection against infection is not essential. The chances of success
      would increase if more than one of the various host/parasite interphases were
      targeted, for example reducing morbidity through decreased worm loads as well as
      through suppression of egg production. Several promising schistosome antigens
      have now reached an advanced phase of development and are currently undergoing
      independent confirmatory testing according to a standardized protocol. A few
      molecules are being contemplated for scaled-up production but, so far, only one
      has reached the stage of industrial manufacture and safety testing. Since
      schistosomiasis cannot realistically be controlled by a single approach,
      vaccination is envisaged to be implemented in conjunction with other means of
      control, notably chemotherapy.

PMID- 8531663
TI  - Health education, public information, and communication in schistosomiasis
      control in Brazil: a brief retrospective and perspectives.
AB  - In recent years, the strategy for the control of schistosomiasis has placed
      increased emphasis on the role of health education, public information, and
      communication. This should, not only bring about specific changes in behavior
      aiming at disease prevention, but also stimulate participation of the community
      in health programs. Beyond this, it is desirable that both community members and
      researchers should seek better life conditions through a transformative social
      action. The present paper addresses these concerns; first, by critically
      reviewing some health education programs that were developed in Brazil, and,
      secondly, by analyzing and suggesting ways to improve this area.

PMID- 8531664
TI  - Development of a vaccine strategy against human and bovine schistosomiasis.
      Background and update.
AB  - Schistosomiasis is a chronic and debilitating parasitic disease that affects over
      200 million people throughout the world and causes about 500,000 deaths annually.
      Two specific characteristics of schistosome infection are of primordial
      importance to the development of a vaccine: schistosomes do not multiply within
      the tissues of their definitive hosts (unlike protozoan parasites) and a partial
      non-sterilizing immunity can have a marked effect on the incidence of pathology
      and on disease transmission. Since viable eggs are the cause of disease
      pathology, a reduction in worm fecundity whether or not accompanied by a
      reduction in parasite burden is a sufficient goal for vaccine induced immunity.
      We originally showed that IgE antibodies played in experimental models a pivotal
      role for the development of protective immunity. These laboratory findings have
      been now confirmed in human populations. Following the molecular cloning and
      expression of a protein 28 kDa protein of Schistosoma mansoni and its
      identification as a glutathion S-transferase, immunization experiments have been
      undertaken in several animal species (rats, mice, baboons). Together with a
      significant reduction in parasite burden, vaccination with Sm28 GST was recently
      shown to reduce significantly parasite fecundity and egg viability leading to a
      decrease in liver pathology. Whereas IgE antibodies were shown to be correlated
      with protection against infection, IgA antibodies have been identified as one of
      the factors affecting egg laying and viability. In human populations, a close
      association was found between IgA antibody production to Sm28 GST and the
      decrease of egg output.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531665
TI  - Current concepts of snail control.
AB  - Schistosomiasis control was impossible without effective tools. Synthetic
      molluscicides developed in the 1950s spearheaded community level control. Snail
      eradication proved impossible but repeated mollusciciding to manage natural snail
      populations could eliminate transmission. Escalating costs, logistical
      complexity, its labour-intensive nature and possible environmental effects caused
      some concern. The arrival of safe, effective, single-dose drugs in the 1970s
      offered an apparently better alternative but experience revealed the need for
      repeated treatments to minimise reinfection in programmes relying on drugs alone.
      Combining treatment with mollusciciding was more successful, but broke down if
      mollusciciding was withdrawn to save money. The provision of sanitation and safe
      water to prevent transmission is too expensive in poor rural areas where
      schistosomiasis is endemic; rendering ineffective public health education linked
      to primary health care. In the tropics, moreover, children (the key group in
      maintaining transmission) will always play in water. Large scale destruction of
      natural snail habitats remains impossibly expensive (although proper design could
      render many new man-made habitats unsuitable for snails). Neither biological
      control agents nor plant molluscicides have proved satisfactory alternatives to
      synthetic molluscicides. Biologists can develop effective strategies for using
      synthetic molluscicides in different epidemiological situations if only, like
      drugs, their price can be reduced.

PMID- 8531666
TI  - Comparison of purified 12 kDa and recombinant 15 kDa Fasciola hepatica antigens
      related to a Schistosoma mansoni fatty acid binding protein.
AB  - Vaccines in schistosomiasis using homologous antigens have been studied
      extensively in experimentally infected mammalian hosts. Vaccines using
      heterologous antigens have received comparatively less attention. This review
      summarizes recent work on a heterologous 12 kDa Fasciola hepatica antigenic
      polypeptide which cross reacts with Schistosoma mansoni. A cDNA has been cloned
      and sequenced, and the predicted amino acid sequence of the recombinant protein
      has been shown to have significant (44%) identity with a 14 kDa S. mansoni fatty
      acid binding protein. Thus in the parasitic trematodes fatty acid binding
      proteins may be potential vaccine candidates. The F. hepatica recombinant protein
      has been overexpressed and purified and denoted rFh15. Preliminary rFh15 migrates
      more slowly (i.e. may be slightly larger) than nFh12 on SDS-PAGE and has a
      predicted pI of 6.01 vs. observed pI of 5.45. Mice infected with F. hepatica
      develop antibodies to nFh12 by 2 weeks of infection vs. 6 weeks of infection to
      rFh15; on the other hand, mice with schistosomiasis mansoni develop antibodies to
      both nFh12 and rFh15 by 6 weeks of infection. Both the F. hepatica and S. mansoni
      cross-reactive antigens may be cross-protective antigens with the protection
      inducing capability against both species.

PMID- 8531667
TI  - Vaccination against schistosomiasis and fascioliasis with the new recombinant
      antigen Sm14: potential basis of a multi-valent anti-helminth vaccine?
AB  - Molecular cloning of components of protective antigenic preparations have
      suggested that related parasite fatty acid binding proteins could form the basis
      of the well documented protective, immune cross reactivity between the parasitic
      trematode worms Fasciola hepatica and Schistosoma mansoni. We have now confirmed
      the cross protective potential of parasite fatty acid binding proteins and
      suggest that it may be possible to produce a single vaccine that would be
      effective against at least two parasites, F. hepatica and S. mansoni of
      veterinary and human importance respectively.

PMID- 8531668
TI  - Control of schistosomiasis in Brazil: perspectives and proposals.
AB  - Attempts to control schistosomiasis have hitherto involved the use of one or more
      of the following methods, either in isolation or in combination: (1) control of
      the intermediate host using molluscicides or biological methods; (2) basic
      sanitation and clean water supply; (3) health education; (4) individual or mass
      treatment; (5) protection of individuals in such a way as to prevent cercariae
      from penetrating the skin; (6) vaccine-based strategies against schistosomiasis.
      None of these methods is capable, on its own, of bringing about effective control
      of schistosomiasis, except in populations of a very limited size or under very
      special conditions. Molluscicides, besides expensive and toxic, have only a
      temporary effect. As for biological control, there is no effective method yet.
      Basic sanitation and clean water supply combined with health education
      potentially constitute the most effective approach, but only in the mid-to-long
      term. Mass treatment reduces morbidity, but does not control transmission.
      Protection of individuals has proved to be impracticable on a large scale.
      Vaccine-based strategies against schistosomiasis are still in the experimental
      stage. Experiments carried out in Brazil in the last 20 years have shown that
      mass treatment with single doses of oxamniquine or praziquantel can rapidly
      reduce levels of Shistosoma mansoni infection and morbidity in endemic areas.
      They have also shown that subsequent transmission and reinfection frequently
      occur in defined foci or "clusters", due to human contact with water, and in
      inverse proportion to the number and frequency of treatments carried out. On the
      basis of these experiments, the author suggests a multidisciplinary strategy for
      schistosomiasis control.

PMID- 8531669
TI  - Current advances on the study of snail-snail interactions, with special emphasis
      on competition process.
AB  - Field work research on population dynamic of snails from the regions of Belo
      Horizonte and Lagoa Santa give much information about interactions among two or
      more species of mollusks: Pomacea haustrum, Biomphalaria glabrata, B.
      tenagophila, B. straminea and Melanoides tuberculata. Data ranging from two years
      to several decades ago suggest that the Pampulha reservoir is like a cemetery of
      B. glabrata and B. straminea, species that coexist for more than 14 years in a
      small part of a stream, whereas only B. glabrata lives in all the streams of the
      basin. In the last ten to twenty years B. tenagophila has coexisted with P.
      haustrum and M. tuberculata in the Serra Verde ponds and in the Pampulha dam.
      However these species have not settled in any of the brooks, except temporarily.
      The data suggest that the kind of biotope and the habitat conditions are decisive
      factors for the permanence of each species in its preferencial biotope. B.
      glabrata, natural from streams and riverheads, quickly disappears from the
      reservoirs and ponds where it coexists with other species for a short time,
      independently of the competitive process. Competition needs to be better studied,
      since in Central America and Caribean islands this kind of study has favored the
      biological control of planorbid species.

PMID- 8531671
TI  - Acute human schistosomiasis mansoni.
AB  - The acute schistosomiasis is the toxemic disease that follow the Schistosoma
      cercariae active penetration trough screen in the immunologicaly naive vertebrate
      host. The clinical picture starts two to eight weeks after the first contact with
      the contaminated water. Susceptible patients present a syndrome comprising fever,
      diarrhea, toxemia and hepatosplenomegaly. Diagnosis is based on epidemiological
      and clinical features, presence of Schistosoma eggs in the feces, enlargement of
      abdominal lymph nodes by ultrasonography and by detection of high antibodies
      levels against the antigen keyhole limpet haemocyanin. Different rates of cure
      have been observed with specific medication and for the most severe clinical
      presentations the use of steroids reduces the systemic and allergic
      manifestations.

PMID- 8531670
TI  - Immuno-epidemiology of Schistosoma mansoni infections in a recently exposed
      community in Senegal.
AB  - Schistosoma mansoni was introduced in the Senegal basin around 1988, due to man
      made ecological changes. Since 1991, we investigate a recent but very intense
      focus, Ndombo, a village near the city of Richard Toll where the outbreak was
      first described. Four cohorts, each a random sample (+/- 400 subjects each) from
      this community, were examined and followed up after treatment, starting at 8
      month intervals over a 2-year period. Each cohort is examined parasitologically
      (Kato-Katz), clinically, serologically (circulating antigen and antibody
      profiles); treated with praziquantel 40 mg/kg; followed up 6-10 weeks, one and
      two years after treatment; and monitored for water contact patterns and local
      snail densities. In the first cohort, the prevalence was 91%, with a mean egg
      count of 663 epg. Prevalences are near 100% in all age groups, but egg counts
      decline strongly in adults. Antigen detection in serum and urine confirmed that
      the egg counts genuinely reflect variations of worm burdens, not e.g. of worm
      fecundity. This is surprising, as in this focus acquired immunity in adults
      should not have yet developed according to current hypothesis. The antigen
      detection assays (CAA/CCA) showed high sensitivity and quantitative power, and
      promising perspectives as a research tool and possibly as a method for non
      invasive diagnosis and screening in urine. Epidemiological in subsequent cohorts
      were highly similar, although seasonal variations were observed possibly due to
      transmission fluctuations. Anti-AWA and anti-SEA IgE levels increased with age,
      while IgG4 peaked in the age-group 10 years and correlated well with egg
      counts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531672
TI  - A molecular genetic study of the variations in metabolic function during
      schistosome development.
AB  - During their complex life cycle schistosomes alternate between the use of stored
      glycogen and reliance on host glucose to provide for their energy needs. In
      addition, there is dramatic variation between the relative contribution of
      aerobic versus anaerobic glucose metabolism during development. We have cloned a
      set of representative cDNAs that encode proteins involved in glucose uptake,
      glycolysis, Kreb's cycle and oxidative phosphorylation. The different cDNAs were
      used as probes to examine the expression of glucose metabolism genes during the
      schistosome life cycle. Steady state mRNA levels from whole cercariae, isolated
      cercarial tails, schistosomula and adult worms were analysed on Northern blots
      and dot blots which were quantified using storage phosphor technology. These
      studies reveal: (1) Transcripts encoding glycogen metabolic enzymes are expressed
      to much higher levels in cercarial tails than whole cercariae or schistosomula
      while the opposite pattern is found for glucose transporters and hexokinase
      transcripts; (2) Schistosomula contain low levels of transcripts encoding
      respiratory enzymes but regain the capacity for aerobic glucose metabolism as
      they mature to adulthood; (3) Male and female adults contain similar levels of
      the different transcripts involved in glucose metabolism.

PMID- 8531673
TI  - Control of schistosomiasis transmission.
AB  - Despite the success of control programmes, schistosomiasis is still a serious
      public health problem in the world. More than 70 countries where 200 million
      individuals are evaluated to be infected of a total 600 million at risk. Though
      there have been important local success in the control of transmission, globally
      the infection has increased. Economic constrains in developing countries,
      environmental changes associated with migration and water resources development
      have been blocking the progress. The main objective of schistosomiasis control is
      to achieve reduction of disease due to schistosomiasis. We discussed the control
      measures like: health education, diagnosis and chemotherapy, safe water supplies,
      sanitation and snail control. We emphasized the need to give priority to school
      age children and the importance of integrating the measures of control into
      locally available systems of health care. The control of schistosomiasis is
      directly related to the capacity of the preventive health services of an endemic
      country. The strategy of control requires long-term commitment from the
      international to the local level.

PMID- 8531674
TI  - Novel mechanisms of immune evasion by Schistosoma mansoni.
AB  - The interaction of Schistosoma mansoni with its host's immune system is largely
      affected by multiple specific and non-specific evasion mechanisms employed by the
      parasite to reduce the host's immune reactivity. Only little is known about these
      mechanisms on the molecular level. The four molecules described below are
      intrinsic parasitic proteins recently identified and studied in our laboratory.
      1. m28--A 28kDa membrane serine protease. m28 cleaves iC3b and can thus restrict
      attack by effector cells utilizing complement receptors (especially CR3).
      Treatment with protease inhibitors potentiates killing of schistosomula by
      complement plus neutrophils. 2. Smpi56--A 56kDa serine protease inhibitor. Smpi56
      binds covalently to m28 and to neutrophil's elastase and blocks their proteolytic
      activity. 3. P70--A 70kDa C3b binding protein. The postulated activity of P70
      includes binding to C3b and blocking of complement activation of the C3 step. 4.
      SCIP-1--A 94kDa schistosome complement inhibitor. SCIP-1 shows antigenic and
      functional similarities to the human 18kDa complement inhibitor CD59. Like CD59,
      SCIP-1 binds to C8 and C9 and blocks formation of the complement membrane attack
      complex. Antibodies directed to human CD59 bind to schistosomula and potentiate
      their killing by complement. The structure and function of these four proteins as
      well as their capacity to induce protection from infection with S. mansoni are
      under investigation.

PMID- 8531675
TI  - Anti-embryonation immunity in murine schistosomiasis japonica (Philippines).
AB  - The hypothesis that granuloma modulation and disease abatement in chronic
      infection with Schistosoma japonicum could be ascribed to antibody-mediated
      effects on egg maturation and egg viability, arose from studies performed with
      mice in the Philippines. This novel hypothesis has not yet been integrated into
      the schistosomiasis literature despite being formulated more than a decade ago.
      One reason for this is that the phenomenon might be confined to S. japonicum,
      even S. japonicum (Philippines).

PMID- 8531676
TI  - Schistosomiasis control in China.
AB  - After three decades' efforts, schistosomiasis japonica were controlled in one
      third (4/12) of endemic provinces and 68.2% (259/380) of endemic counties
      throughout the country. The remaining 121 endemic counties are located primarily
      in the lake and mountainous regions. The epidemiological and ecological features
      of the lake and mountainous areas are different from the other endemic areas. The
      major schistosomiasis control efforts in China can be characterized as follows:
      (1) Application of centralized leadership and management, since schistosomiasis
      control is a task not only of the Ministry of Public Health, but also of all
      local governments in the endemic areas; (2) Integration of actions taken by
      various departments or bureaus, such as agriculture, water conservation and
      public health; (3) Promotion of mass participation; (4) Organization of strong
      professional teams; (5) Raising sufficient funds. Strategies on schistosomiasis
      control applied in different areas are divided into three levels: (1) In the
      areas where the schistosomiasis has been successfully controlled, surveillance
      must be maintained and immediate action should be taken where new infections
      occur and/or vector snails are found, so that control can be reestablished
      quickly; (2) In the areas where schistosomiasis has been partially controlled,
      any residents and/or live-stock infected should be examined and treated promptly
      with due care, and environment modifying and/or mollusciding must be used to
      eliminate the remaining snails; (3) In the areas where transmission has not been
      controlled, the main strategy is to control morbidity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8531677
TI  - Schistosomiasis control in a primary health care system.
AB  - The successful implementation of a Primary Health Care System (PHC) in any
      country depends primarily on the ability to adapt its concepts and principles to
      the country's culture and development stage. Thus, the PHC system should reflect
      a balanced interaction between available resources, such as health manpower
      capabilities, and the nature and magnitude of the health problems. In addition,
      PHC should be viewed as the inlet to a multi-level pyramidal health system which
      caters to both community and individual needs in a balanced way. The adage that
      Ministries of Health should "work with and for the people" in health development,
      is especially true in the area of PHC, and hence, the health policy should aim to
      integrate health services in community development and involve people in its
      planning, implementation and evaluation.

PMID- 8531678
TI  - [Schistosomiasis control in the State of Sao Paulo].
AB  - The program of schistosomiasis control for the State of Sao Paulo, where only low
      endemicity areas occur, is discussed in this paper. Inclusion of schistosomiasis
      among the diseases due to obligatory notification is considered as a measure of
      great importance. Accordingly the search for passive cases conducted by the
      public health system acquired major importance in the disease surveillance. As
      from 1981 to 1992 only 11% of the detected cases were considered as
      autochthonous. The main transmission areas are located at the Litoral and Paraiba
      Valley regions. In the period of time under analysis, the epidemiological
      surveillance data suggest a decrease in the morbidity and in the autochthony
      tendency in the State of Sao Paulo.

PMID- 8531679
TI  - Calomys callosus: an alternative model to study fibrosis in schistosomiasis
      mansoni. The pathology of the acute phase.
AB  - Twenty Calomys callosus, Rengger, 1830 (Rodentia-Cricetidae) were studied in the
      early stage of the acute schistosomal mansoni infection (42nd day). The same
      number of Swiss Webster mice were used as a comparative standard. Liver and
      intestinal sections, fixed in formalin-Millonig and embedded in paraffin, were
      stained with hematoxilin and eosin, PAS-Alcian Blue, pH = 1.0 and 2.5, Lennert's
      Giemsa, Picrosirius plus polarization microscopy, Periodic acid methanamine
      silver, Gomori's silver reticulin and resorcin-fuchsin. Immunohistological study
      (indirect immunofluorescence and peroxidase labeled extravidin-biotin methods)
      was done with antibodies specific to pro-collagen III, fibronectin, elastin,
      condroitin-sulfate, tenascin, alpha smooth muscle actin, vimentin and desmin. The
      hepatic granulomas were small, reaching only 27% of the volume of the hepatic
      Swiss Webster granuloma. They were composed mainly by large immature macrophages,
      often filled by schistosomal pigment, characterizing an exsudative-macrophage
      granuloma type. The granulomas were situated in the parenchyma and in the portal
      space. They were often intravascular, poor of extracellular matrix components,
      except fibronectin and presented, sometimes alpha smooth muscle actin and
      vimentin positive cells. The C. callosus intestinal granulomas were similar to
      Swiss Webster, showing predominance of macrophages. Therefore, the C. callosus
      acquire very well the Schistosoma mansoni infection, without developing strong
      hepatic acute granulomatous reaction, suggesting lack of histopathological signs
      of hypersensitivity.

PMID- 8531680
TI  - Cell synchronization.

PMID- 8531681
TI  - Analysis of cell cycle checkpoint status in mammalian cells.

PMID- 8531682
TI  - Microcell fusion.

PMID- 8531683
TI  - Tumor cell culture.

PMID- 8531684
TI  - Superfamilies of protooncogenes: homology cloning and characterization of related
      members.

PMID- 8531685
TI  - Polymerase chain reaction cloning of related genes.

PMID- 8531686
TI  - Isolation of oncogenes by expression cDNA cloning.

PMID- 8531687
TI  - Generation and culturing of precursor cells and neuroblasts from embryonic and
      adult central nervous system.

PMID- 8531688
TI  - Replication-competent and -defective retrovirus vectors for oncogenic studies.

PMID- 8531689
TI  - Identification of protein-protein interactions by lambda gt11 expression cloning.

PMID- 8531690
TI  - Analyzing protein-protein interactions using two-hybrid system.

PMID- 8531691
TI  - Retrovirus gene traps.

PMID- 8531692
TI  - Fingerprinting of DNA and RNA by arbitrarily primed polymerase chain reaction:
      applications in cancer research.
AB  - RNA fingerprinting by RAP-PCR is a powerful tool for the temporal and spatial
      analysis of differential gene expression. Many biological situations exist where
      differential gene expression results in distinguishable phenotypes, including,
      for example, tissue and cell types, responses to hormones, growth factors,
      stress, and the heterologous expression of certain genes. There are several
      methods for detecting differential gene expression and cloning differentially
      expressed genes that do not rely on a biological assay of phenotype. Most of
      these methods fall into two general categories: subtractive hybridization and
      differential screening. RAP-PCR offers numerous advantages over these methods,
      including its simplicity and its ability to compare the fluctuations in gene
      expression between multiple samples simultaneously using minute amounts of RNA.
      In addition, RAP-PCR can yield information on the overall patterns of gene
      expression between different cell types or between different physiological
      conditions of the same cell type. Comparison of the RAP-PCR fingerprints from
      these different experimental groups permits one to draw inferences regarding the
      overall cellular states of gene expression and the interrelation between gene
      transcripts belonging to the same or different regulatory pathways. Hypotheses
      regarding signal transduction pathways can be obtained using this information.
      RAP-PCR offers applications in cancer research in the detection of tumor-specific
      alterations in gene expression, providing a bountiful source of tumor markers.
      The pleiotropic impact of oncogene activation, tumor suppressor gene
      inactivation, and mutator mutations, in gene regulation, can be readily assessed
      by RAP-PCR in model systems both in vitro and in vivo.

PMID- 8531693
TI  - Representational difference analysis in detection of genetic lesions in cancer.

PMID- 8531694
TI  - Isolation and utilization of epidermal keratinocytes for oncogene research.

PMID- 8531695
TI  - Analysis of altered gene expression by differential display.

PMID- 8531696
TI  - Approaches to the identification and molecular cloning of chromosome breakpoints.

PMID- 8531697
TI  - Detection of chromosomal aberrations by means of molecular cytogenetics: painting
      of chromosomes and chromosomal subregions and comparative genomic hybridization.

PMID- 8531698
TI  - Antisense techniques.

PMID- 8531699
TI  - Transformation of primary rat embryo cells.

PMID- 8531700
TI  - Use of lac activator proteins for regulated expression of oncogenes.

PMID- 8531701
TI  - Lineage analysis using retrovirus vectors.

PMID- 8531702
TI  - Avian hematopoietic cell culture: in vitro model systems to study oncogenic
      transformation of hematopoietic cells.

PMID- 8531703
TI  - In situ hybridization.

PMID- 8531704
TI  - Monoclonal antibodies to oncoproteins.

PMID- 8531705
TI  - Microinjection of antibodies.

PMID- 8531706
TI  - Microinjection into Xenopus oocytes.

PMID- 8531707
TI  - Regulatable chimeric oncogenes.

PMID- 8531708
TI  - Use of tetracycline operator system to regulate oncogene expression in mammalian
      cells.

PMID- 8531709
TI  - Detection of protein-protein interactions by coimmunoprecipitation and
      dimerization.

PMID- 8531710
TI  - Epitope tagging.

PMID- 8531711
TI  - Biochemical analysis of SH2 domain-mediated protein interactions.

PMID- 8531712
TI  - SH2 domain specificity determination using oriented phosphopeptide library.

PMID- 8531713
TI  - Rapid high-resolution western blotting.

PMID- 8531715
TI  - Transdominant negative mutations.

PMID- 8531714
TI  - Phosphorylation of transcription factors.
AB  - Many transcription factors are regulated by post-translational phosphorylation
      mechanisms. This chapter described several approaches that have been utilized to
      examine the phosphorylation of the c-Jun transcription factor. A combination of
      the techniques described in this chapter can be used to determine whether a
      transcription factor is phosphorylated in vivo, to analyze the sites of
      phosphorylation in vitro, and to permit the identification of putative protein
      kinases that may mediate this phosphorylation in vivo. Proteins labeled with 32P
      by either in vivo or in vitro techniques can be further analyzed by tryptic
      phosphopeptide mapping or phosphoamino acid analysis. These procedures have been
      described in detail elsewhere.

PMID- 8531716
TI  - Mapping DNA-protein interactions in cells and nuclei: genomic sequencing by
      template purification.

PMID- 8531717
TI  - DNA affinity chromatography.

PMID- 8531718
TI  - Selection of protein binding sites from random nucleic acid sequences.

PMID- 8531719
TI  - Electrophoretic mobility shift assay.

PMID- 8531720
TI  - Ultraviolet cross-linking of DNA binding proteins.

PMID- 8531721
TI  - Avian neuroretina cells in oncogene studies.

PMID- 8531722
TI  - Myogenic and chondrogenic cells.

PMID- 8531723
TI  - Mosaic analysis.

PMID- 8531724
TI  - Genetic balancers.

PMID- 8531725
TI  - Genetic pharmacology: interactions between drugs and gene products in
      Caenorhabditis elegans.

PMID- 8531726
TI  - Methods of studying behavioral plasticity in Caenorhabditis elegans.

PMID- 8531727
TI  - Laser killing of cells in Caenorhabditis elegans.

PMID- 8531728
TI  - Electrophysiological methods.

PMID- 8531729
TI  - Cell biology of nematode sperm.

PMID- 8531730
TI  - Basic culture methods.

PMID- 8531731
TI  - Blastomere culture and analysis.

PMID- 8531732
TI  - Mutagenesis.
AB  - Choosing the right mutagen means selecting the right combination of mutagen
      efficiency and mutagen specificity. For mutagen efficiency, nothing beats EMS. It
      is extremely potent, it is easy to use, and its mutational specificity is well
      documented. If mutations other than G/C-->A/T transitions are desired, mutagens
      other than EMS must be used. Based on initial observations, ENU appears to be as
      efficient as EMS. Work with other organisms predicts that ENU will yield a wider
      variety of transitions and transversions than EMS. If this proves to be true, ENU
      will become an important mutagen for routine genetic analysis. For investigators
      wanting large multigene deletions, gamma irradiation, UV irradiation,
      formaldehyde, and DEO are the mutagens of choice. Gamma irradiation yields the
      highest frequency of events by far, but may also yield more complex
      rearrangements. Based on limited information, UV irradiation, formaldehyde, and
      DEO appear to be effective deletion mutagens. Of the three, UV appears to be the
      most efficient. For investigators wanting small intragenic deletions, TMP appears
      most effective. TMP is not very potent, but a large proportion of TMP-induced unc
      22 mutations are small deletions. Hopefully this will be true of all genes. For
      investigators wanting other types of genome rearrangements (e.g., translocations,
      crossover suppressors), gamma irradiation (or possibly X irradiation) is
      effective. For transposon insertions, mut-2 (especially strain TR679) provides
      the highest possible frequency of events. Because mut-2 activates several
      families of transposons, it yields insertions in genes that are poor targets for
      Tc1. Manipulating a strain with such high frequencies of spontaneous mutations,
      however, can be problematical (see above). For Tc1-specific events, mut-6 (strain
      RW7097) is the best choice. It provides frequencies comparable to those of
      Bergerac, but its Tc1 copy number is much lower. A reasonable strategy for
      spontaneous mutagenesis is to use TR679 only if mutants are not obtained in
      strains with lower levels of activity (e.g., MT3126 or RW7097).

PMID- 8531733
TI  - Whole-mount in situ hybridization for the detection of RNA in Caenorhabditis
      elegans embryos.

PMID- 8531734
TI  - Fluorescence in situ hybridization for the detection of DNA and RNA.

PMID- 8531735
TI  - Immunofluorescence microscopy.

PMID- 8531736
TI  - Electron microscopy and three-dimensional image reconstruction.

PMID- 8531737
TI  - Proteins and protein assemblies.

PMID- 8531738
TI  - DNA transformation.

PMID- 8531739
TI  - Transcription and translation.

PMID- 8531740
TI  - Techniques for analyzing transcription and translation.

PMID- 8531741
TI  - The physical map of the Caenorhabditis elegans genome.

PMID- 8531742
TI  - Genomic DNA sequencing methods.
AB  - Sequence analysis of cosmids from C. elegans and other organisms currently is
      best done using the random or "shotgun" strategy (Wilson et al., 1994). After
      shearing by sonication, DNA is used to prepare M13 subclone libraries which
      provide good coverage and high-quality sequence data. The subclones are assembled
      and the data edited using software tools developed especially for C. elegans
      genomic sequencing. These same tools facilitate much of the subsequent work to
      complete both strands of the sequence and resolve any remaining ambiguities.
      Analysis of the finished sequence is then accomplished using several additional
      computer tools including Genefinder and ACeDB. Taken together, these methods and
      tools provide a powerful means for genome analysis in the nematode.

PMID- 8531743
TI  - Large-scale complementary DNA sequencing methods.
AB  - Complementary DNA libraries are useful tools for uncovering genes of interest in
      C. elegans and finding specific homologies to genes in other organisms (Waterston
      et al., 1992; McCombie et al., 1992). When working with existing cDNA libraries,
      be sure to carefully choose which libraries would be most beneficial to the type
      of research being done. Some libraries may be specific for genes that are present
      in lower copy numbers, whereas others may be of a more general nature. It is
      important to fully understand the source and construction of the library you will
      be working with. Once an appropriate library has been chosen, work may begin to
      isolate a specific cDNA and sequence it completely or to survey many cDNAs by
      single-pass DNA sequencing. Whatever the project, it is important to develop a
      specific strategy for both the sequencing and the organization of the clones
      being characterized. The strategies and procedures we have outlined in this
      chapter have proven effective for rapid and comprehensive cDNA characterization.

PMID- 8531744
TI  - ACeDB and macace.

PMID- 8531745
TI  - Reverse genetics: from gene sequence to mutant worm.

PMID- 8531746
TI  - The Worm Community System, release 2.0 (WCSr2).

PMID- 8531747
TI  - Genetic mapping with polymorphic sequence-tagged sites.

PMID- 8531748
TI  - Genetic dissection of developmental pathways.

PMID- 8531749
TI  - Confocal epipolarization microscopy of gold probes in plant cells and
      protoplasts.

PMID- 8531750
TI  - Monoclonal antibodies to cell-specific cell surface carbohydrates in plant cell
      biology and development.

PMID- 8531751
TI  - Epitope tagging for the detection of fusion protein expression in transgenic
      plants.

PMID- 8531752
TI  - In situ enzyme histochemistry on plastic-embedded plant material.

PMID- 8531753
TI  - In situ hybridization.

PMID- 8531754
TI  - Localization of RNA by high resolution in situ hybridization.

PMID- 8531755
TI  - Recombinant aequorin methods for intracellular calcium measurement in plants.

PMID- 8531756
TI  - Ion localization and X-ray microanalysis.

PMID- 8531757
TI  - Confocal microscopy of the shoot apex.

PMID- 8531758
TI  - Measurements of wall stress relaxation in growing plant cells.

PMID- 8531759
TI  - High-resolution NMR methods for study of higher plants.

PMID- 8531760
TI  - Electrophysiology.

PMID- 8531761
TI  - Ion-selective microelectrodes for measurement of intracellular ion
      concentrations.

PMID- 8531762
TI  - Patch-clamping plant cells.

PMID- 8531763
TI  - Advances in high-pressure and plunge-freeze fixation.

PMID- 8531764
TI  - Methods for mesophyll and bundle sheath cell separation.

PMID- 8531765
TI  - Synchronization of cell cultures of higher plants.

PMID- 8531766
TI  - Freeze-fracture deep-etch methods.

PMID- 8531767
TI  - Genetic tagging of cells and cell layers for studies of plant development.

PMID- 8531768
TI  - Chemically induced mitotic synchrony in root apical meristems.

PMID- 8531769
TI  - Manipulation of pollen grains for gametophytic and sporophytic types of growth.

PMID- 8531770
TI  - Root border cells as tools in plant cell studies.

PMID- 8531771
TI  - In vivo footprinting of protein-DNA interactions.

PMID- 8531772
TI  - The interaction trap: in vivo analysis of protein-protein associations.

PMID- 8531773
TI  - Cloning plant genes by complementation of yeast mutants.

PMID- 8531774
TI  - Differential mRNA display.

PMID- 8531775
TI  - Molecular methods for isolation of signal transduction pathway mutants.

PMID- 8531776
TI  - Advances in immunoelectron microscopy.

PMID- 8531777
TI  - Induction of signal transduction pathways through promoter activation.

PMID- 8531778
TI  - In vitro analysis of G-protein functions.

PMID- 8531779
TI  - Production of recombinant plant calmodulin and its use to detect calmodulin
      binding proteins.

PMID- 8531780
TI  - Analysis of the light signaling pathway in stomatal guard cells.

PMID- 8531781
TI  - Immunocytochemical localization of receptor protein kinases in plants.

PMID- 8531782
TI  - Expression and assay of autophosphorylation of recombinant protein kinases.

PMID- 8531784
TI  - Freeze-substitution.

PMID- 8531783
TI  - Transmembrane signaling and phosphoinositides.

PMID- 8531785
TI  - Cell optical displacement assay (CODA)--measurements of cytoskeletal tension in
      living plant cells with a laser optical trap.

PMID- 8531786
TI  - Methods in plant immunolight microscopy.

PMID- 8531787
TI  - Isolation and characterization of plant nuclei.

PMID- 8531788
TI  - Isolation of nuclei suitable for in vitro transcriptional studies.

PMID- 8531789
TI  - Analysis of the H(+)-ATPase and other proteins of the Arabidopsis plasma
      membrane.

PMID- 8531790
TI  - Isolation and functional reconstruction of the vacuolar H(+)-ATPase.

PMID- 8531791
TI  - Functional effects of structural changes in photosystem II as measured by
      chlorophyll fluorescence kinetics.

PMID- 8531792
TI  - Isolation and fractionation of plant mitochondria and chloroplasts: specific
      examples.

PMID- 8531793
TI  - Isolating the plant mitotic apparatus: a procedure for isolating spindles from
      the diatom Cylindrotheca fusiformis.

PMID- 8531794
TI  - Chromoplasts.

PMID- 8531795
TI  - Methods for isolation and analysis of polyribosomes.

PMID- 8531796
TI  - Methods for isolation and analysis of the cytoskeleton.

PMID- 8531797
TI  - Isolation and characterization of plasmodesmata.

PMID- 8531798
TI  - Characterization and isolation of the chloroplast protein import machinery.

PMID- 8531799
TI  - Macromolecular movement into mitochondria.

PMID- 8531801
TI  - Import into the endoplasmic reticulum.

PMID- 8531800
TI  - Targeting of proteins to the nucleus.

PMID- 8531802
TI  - Flow cytometric analysis of transgene expression in higher plants: green
      fluorescent protein.

PMID- 8531803
TI  - Protein--protein interactions within the endoplasmic reticulum.

PMID- 8531804
TI  - Determination of protein isoprenylation in vitro and in vivo.

PMID- 8531805
TI  - Assaying proteins for molecular chaperone activity.

PMID- 8531806
TI  - The use of protoplasts to study protein synthesis and transport by the plant
      endomembrane system.

PMID- 8531807
TI  - Assessment of translational regulation by run-off translation of polysomes in
      vitro.

PMID- 8531808
TI  - Electroporation of plant protoplasts and tissues.

PMID- 8531809
TI  - Particle bombardment.

PMID- 8531810
TI  - Preparation and transformation of monocot protoplasts.

PMID- 8531811
TI  - Tobacco protoplast transformation and use for functional analysis of newly
      isolated genes and gene constructs.

PMID- 8531812
TI  - Extraction and assay of protein from single plant cells.

PMID- 8531813
TI  - Novel inducible/repressible gene expression systems.

PMID- 8531814
TI  - Reporter genes.

PMID- 8531815
TI  - Cell-specific ablation in plants.

PMID- 8531816
TI  - Ribozymes.

PMID- 8531817
TI  - Expression of plant proteins in baculoviral and bacterial systems.

PMID- 8531818
TI  - Expression and localization of plant membrane proteins in Saccharomyces.

PMID- 8531819
TI  - Synthesis of plant proteins in heterologous systems: Xenopus laevis oocytes.

PMID- 8531820
TI  - Photoaffinity labeling and strategies for plasma membrane protein purification.

PMID- 8531821
TI  - Heterologous expression of higher plant transport proteins and repression of
      endogenous ion currents in Xenopus oocytes.

PMID- 8531822
TI  - Cell cycle synchronization, chromosome isolation, and flow-sorting in plants.

PMID- 8531823
TI  - Principles and applications of recombinant antibody phage display technology to
      plant biology.

PMID- 8531824
TI  - The story behind the creation of the Michigan AIDS Fund.

PMID- 8531825
TI  - Physicians and grief: a paradigm shift.

PMID- 8531826
TI  - Empowering physicians for the future.

PMID- 8531827
TI  - Thriving in a managed care environment.

PMID- 8531828
TI  - Update on physician self-referral and medical malpractice arbitration.

PMID- 8531829
TI  - Insulin receptor alpha-subunit: a putative gene regulatory molecule.
AB  - Previous studies have demonstrated the presence of the insulin receptor in the
      cell nucleus. Recently, it was shown that the insulin receptor also exhibits
      nuclear tyrosine kinase activity. In the present investigation, I have searched
      for structural correlates to a nuclear localization of the insulin receptor as
      well as to other potential nuclear actions of this molecule. Interestingly, this
      analysis yielded that the insulin receptor (alpha-subunit) contains a bipartite
      nuclear localization signal (consistent with the preceding experimental data),
      several zinc finger-like motifs and an RGG box. These findings have intriguing
      implications with regard to a presumable role of the insulin receptor (alpha
      subunit) as a gene regulatory molecule.

PMID- 8531830
TI  - Detection of hepatitis B virus transcriptional activity: an hypothesis.
AB  - This paper outlines a method of demonstrating hepatitis B virus (HBV)-related
      transcriptional activity based on the random amplification of cDNA ends (RACE)
      protocol. Following RNA extraction from the appropriate tissue, cDNA is
      synthesized using a long oligo d(T) based primer containing unique 5'
      oligonucleotide sequences. Nested polymerase chain reaction (PCR) is then carried
      out using virus-specific oligonucleotides and standard PCR (approximately 20 base
      pairs) oligonucleotides homologous to 5' regions of the long oligo-d(T) primer
      used to initiate the cDNA reaction. This technique is particularly applicable to
      the study of HBV transcription in small samples of tissue, for example, from
      renal biopsies obtained from patients with HBV-related nephritis.

PMID- 8531831
TI  - The colonisation of Europe and our Western diseases.
AB  - Correspondence of fat intake with civilisatory diseases (coronary disease and
      cancer) is usually attributed to adverse effects of animal fat and cholesterol.
      The 'field studies' themselves, undertaken to support this theory, failed. As the
      last environmental changes in human history are agriculture and rise of
      carbohydrate intake (and concomitant reduction of fat and protein consumption),
      the author thinks that the carbohydrates rather than the animal fats cause our
      civilisatory diseases. It can be shown that the spread of agriculture from the
      Near East to the West and North of Europe with the accompanying differences in
      time for the adaptation to the new food (the carbohydrates) easily explains the
      geographic differences in the frequency of civilisatory diseases which is highest
      where (in Northern Ireland, Scotland and Finland) carbohydrates came last.
      Highest, too, in those areas is the 'polymorphism' of genes which are related to
      cardiovascular diseases (ACE, apolipoprotein-B etc.) This 'adaptation theory'
      explains also the hitherto unexplained up and down of cardiovascular disease in
      the USA by immigration from regions with higher adaptation to carbohydrates.

PMID- 8531832
TI  - Thyroid therapy in HIV-infected patients.
AB  - Ten HIV-positive patients were given thyroid hormone in pharmacological doses.
      Two patients that had CD4 counts of 200 or higher responded well with gain in
      weight, energy, endurance and well-being within 6 months. During the same period,
      their CD4 counts rose to within normal limits and remained there. One patient has
      been well for 3 years and the other for 1 year. Six other patients with counts
      below 200 have had variable clinical improvements during the first 6 months but
      no change in CD4 counts. Thyroid therapy in pharmacological doses helps most
      patients with symptoms of fatigue or depression. At the same time, it may retard
      or prevent the progression from HIV infection to AIDS.

PMID- 8531833
TI  - Carbamylation of proteins and atherogenesis in renal failure.
AB  - The incidence of atherosclerosis is greatly increased in patients with chronic
      renal failure, and this increased risk is only partly explained by conventional
      risk factors. Carbamylation of proteins occurs in renal failure as a result of
      reactions between urea-derived cyanate and protein amino groups. A mechanism is
      proposed whereby oxidation of LDL cholesterol within the arterial wall may be
      enhanced as a result of carbamylation. This may be accentuated as a result of
      inhibition of antioxidant enzymes by carbamylation. The combination of these
      processes may lead to increased atherogenesis.

PMID- 8531834
TI  - A strategy for the detection of de novo synthesis of nucleic acids: an
      hypothesis.
AB  - This paper outlines novel strategy for demonstrating de novo synthesis of nucleic
      acids applicable, at least, to the detection of viral replication within cell
      culture or other in vitro systems. The method uses an incorporation capture
      technique which is suitable for the detection of new and on-going synthesis of
      both RNA and DNA of any specific sequence. When combined with random RNA (or DNA)
      amplification by polymerase chain reaction (PCR), and subsequent application of
      well established cloning techniques, this strategy will allow the construction
      cDNA libraries of newly synthesized RNAs.

PMID- 8531835
TI  - Sequence-independent identification of infectious pathogens: an hypothesis.
AB  - This paper presents a theoretical polymerase chain reaction (PCR)-based strategy
      for identification of infectious pathogens independent of either the sequence or
      the nature of the genomic nucleic acid. Total nucleic acid purified from simple
      clinical fluids (such as serum or cerebrospinal fluid) from a patient is randomly
      amplified and cloned and then probed with labeled nucleic acid similarly
      amplified from a second patient. Positive clones are then characterized by
      standard sequencing techniques. Such methodology is applicable to the
      investigation of diseases in which chronic infection may play an etiologic role.

PMID- 8531836
TI  - The macrophage-T-lymphocyte theory of schizophrenia: additional evidence.
AB  - Chronically activated macrophages and T-lymphocytes, along with excessive
      interleukin-2 and other cytokine secretions, were previously proposed as the
      fundamental mediators of schizophrenia. This paper provides further support for
      the immune model of schizophrenia, including evidence on neurotransmitter
      abnormalities, the low amplitude of the auditory P300 event-related potential,
      the neurodevelopmental model of schizophrenia and the possible involvement of the
      locus ceruleus in schizophrenia.

PMID- 8531837
TI  - Isolation of candidate genes by subtractive and sequential (Boolean)
      hybridization: an hypothesis.
AB  - This paper describes a theoretical method of isolating candidate disease-specific
      genes by polymerase chain reaction (PCR)-based subtractive hybridization and
      subsequent (Boolean) hybridization of the subtracted library to arrays of
      chromosome-specific cosmid clones. A specific application of this technique to
      isolate genes potentially related to Wilson's disease is outlined.

PMID- 8531838
TI  - Neuropoiesis: proposal for a connectionistic neurobiology.
AB  - Given current assumptions about the biology of neural organization, some
      connectionists believe that it may not be possible to accurately model the
      brain's neural architecture. We have identified five restrictive neurobiological
      dogmas that we believe have limited the exploration of more fundamental
      correlations between computational and biological neural networks. We postulate
      that: 1) the dendritic tree serves as a synapse storage device rather than a
      simple summation device; 2) connection strength between neurons depends on the
      number and location of synapses of similar weight, not on synapses of variable
      weights; 3) axonal sprouting occurs regularly in adult organisms; 4) the
      postsynaptic genome directly controls the presynaptic cell via mRNA, rather than
      indirectly by the expression of NCAMs, reverse neurotransmitters, etc.; 5)
      dendritic spines serve a trophic function by controlling development of new
      sprouts via a process we term retroduction. We entertain an alternative
      formulation of a computational neural element that is fully consistent with
      modern neuroscience research. We then show how our model neuron can learn under
      Hebbian conditions, and extend the model to explain non-Hebbian, one-trial
      learning. This work is significant because by stretching the theoretical
      boundaries of modern neuroscience, we show how connectionists can potentially
      create new, more biologically-based neural elements which, when, interconnected
      into networks, exhibit not only properties of existing backpropagation networks,
      but other physiological properties as well.

PMID- 8531839
TI  - Leukocyte adhesion molecules as a cofactor in AIDS: basic science and pilot
      study.
AB  - It is well known that the AIDS pandemic is a consequence of pandemic HIV
      infection. However, Koch's postulates are not satisfied for two reasons: 1) AIDS
      cannot be experimentally produced in animals susceptible to HIV infection and 2)
      some people have AIDS (idiopathic CD4+ T lymphocytopenia) in the absence of HIV
      infection. It follows that there is a human immunologic cofactor (HIC) that
      causes AIDS when certain other conditions are satisfied, and the most common of
      these other conditions (but not the only one) is HIV infection. Results from
      microbiology make leukocyte adhesion molecules a good candidate for the HIC. We
      have tested this hypothesis with a pilot study in which a small number of
      patients with HIV disease were infused with a monoclonal mouse antibody (MmAb)
      directed against an LFA-1 adhesion epitope, and then with F(ab) and F(ab)2'
      fragments that bind to the same epitope but are nonimmunogenic. Both agents
      reduced peripheral viral burden significantly but fragments were more effective
      in this respect than the MmAb due to the mitogenic properties of the latter. For
      the same reason, only the MmAb were highly effective in raising circulating
      levels of single and double-marked CD4+ T lymphocytes, with a correlated
      resolution of cutaneous anergy.

PMID- 8531840
TI  - The estrogen connection: the etiological relationship between diabetes, cancer,
      rheumatoid arthritis and psychiatric disorders.
AB  - For some considerable time, there has been a growing awareness that defective
      essential fatty acid metabolism plays a causal role in the pathogenesis of both
      schizophrenia and non-insulin-dependent diabetes mellitus (NIDDM) but the
      influence of defective essential fatty acid metabolism in the pathogenesis of
      rheumatoid arthritis and cancer is less well appreciated. An EFA deficiency, or
      defective EFA metabolism, negatively influences prostaglandin synthesis and
      glucose regulation and transport. Moreover, defective EFA metabolism negatively
      influences estrogen availability which contributes to the observed gender bias
      some of these illnesses manifest. While fluctuations of estrogen are known to
      contribute to the pathogenesis of these conditions, so also do fluctuations of
      IGF-II and there is some suggestion that IGF-II and insulin may well be inversely
      regulated. In addition, insulin-dependent diabetes mellitus (IDDM), rheumatoid
      arthritis, and schizophrenia are thought to be autoimmune disorders, while cancer
      is associated with immune system failure. Consequently, this paper aims to
      examine the pathophysiological similarities and differences between mental
      illness, diabetes, rheumatoid arthritis and cancer in respect of which the causal
      relationship that obtains between essential fatty acids, estrogen, IGF-II,
      glucose regulation and autoimmunity will be addressed.

PMID- 8531841
TI  - The biology of deception: the reluctance to accept the cognitive animal.
AB  - Cognitive ability did not appear de novo in man. Despite our ability to recognize
      limited cognitive behavioral characteristics in animals, there has been no outcry
      to proclaim this phenomenon. Man's image of himself solely possessing cognition
      has taken advantage of the illusory potential in intersubjectivity and placed him
      outside of reality. This deception, however, has positive survival value since it
      is man's self-proclaimed responsibility to excel beyond other simple animal
      species. However, at this point in evolution, we must allow our cognitive ability
      to reform itself and, in so doing, evolve with the benefit of the knowledge that
      this ability is itself creating. By recognizing that animals may have limited
      cognitive ability, we only enhance our self-esteem, not diminish it.

PMID- 8531842
TI  - Central insulin may up-regulate thyroid activity by suppressing neuropeptide Y
      release in the paraventricular nucleus.
AB  - Down-regulation of thyroid activity during underfeeding or diabetes - and
      upregulation during overfeeding - have not been adequately explained.
      Experimental findings suggest that hypothalamic secretion of thyrotropin
      releasing hormone (TRH) is modulated by feeding status; neuropeptide Y may be a
      key mediator of this modulation. I propose that insulin, acting centrally as a
      signal of carbohydrate availability, promotes TRH secretion by inhibiting release
      of neuropeptide Y in the paraventricular nucleus. This mechanism may contribute
      to the weight loss reported during administration of certain insulin-sensitizing
      agents, and observed during low-fat diets.

PMID- 8531843
TI  - Trypsin inhibition: a potential cause of cobalamin deficiency common to the
      pathogenesis of Alzheimer-type dementia and AIDS dementia complex?
AB  - There is increasing evidence for an association between Alzheimer-type dementia
      (AD) and nutritionally independent cobalamin deficiency. Furthermore, low serum
      cobalamin values occur in a kindred with familial Alzheimer's disease (FAD) and
      histopathological confirmation of AD neuropathology. The Cobalamin deficiency
      could be either a consequence or cause of amyloidogenesis. Cobalamin deficiency
      is also associated with the acquired immunodeficiency syndrome (AIDS). A common
      pathogenic mechanism may exist for AIDS dementia complex (ADC) and AD, but there
      is no explanation at present for these associations. This paper presents the
      hypothesis that protease inhibition is a common factor in AD and ADC resulting in
      protein-bound cobalamin malabsorption and disrupted cobalamin metabolism.

PMID- 8531844
TI  - Endothelium, fibrinolysis, cardiac risk factors, and prostaglandins: a unified
      model of atherogenesis.
AB  - A model of atherogenesis is described in which it is proposed that a state of
      relative impairment of intravascular fibrinolytic function is the primary defect
      which makes possible both the initiation and the continued progression of
      arterial plaques. The key mechanism by which impaired fibrinolysis is atherogenic
      centers on the unique disruptive effect which fibrin has on the contiguous
      endothelium of the vascular intimal surface. From this perspective, in areas of
      spontaneous endothelial injury, impaired fibrinolysis maintains and promotes the
      gradual enlargement of the area of injury by causing persistently increased
      intimal permeability and by allowing enhanced fibrin and platelet deposition.
      This hypothesis thus represents a modification of the response-to-injury
      hypothesis in which the emphasis has been shifted from the initial endothelial
      injury to a state of interference with the normal process of healing endothelial
      injuries. Consistent with this viewpoint, it is noted that all positive risk
      factors for vascular disease are associated with impairment of fibrinolytic
      function and, conversely, negative cardiac risk factors enhance fibrinolysis. It
      is further proposed that one or more prostaglandins, or closely related
      metabolites, represent the mediators of primary physiologic importance with
      regard to in vivo regulation of fibrinolysis. By this hypothesis, adequate
      dietary intake of essential fatty acids, as well as maintenance of unimpaired
      eicosanoid metabolism, become centrally important in both preventing and
      reversing arteriosclerosis. This two-tiered model can be used to organize and
      potentially explain the interrelationship between diverse and apparently
      divergent sets of epidemiological data which previous models have been unable to
      accommodate.

PMID- 8531845
TI  - The 'infective' process in scrapie and human spongiform encephalopathy disease.
AB  - It is suggested that spongiform encephalopathy (SE) disease transmission does not
      occur by any classically defined 'infective' process. Rather, it is the case that
      conformationally altered prions in diseased animals are able, by targeting what
      may be an inherited, widely distributed, endogenous retroviral fragment,
      comprising the prion 'gene' system, to initiate the escalating synthesis of
      similar, but host-specified protein. Both initiation and the resulting
      progression are controlled and regulated by endogenous host genetic and other
      factors. While the prion system appears to be primarily involved, the intrinsic
      sequences of the invading prions also have a role in what appears to be a joint
      operation. A parallel may be drawn with EAE in that the disease is initiated by a
      small (myelin basic) protein, and in which, similarly, the ongoing process is
      host-specified, and regulated by genetic and other factors. The presence of
      polynucleotide in 'infective' inocula is probably unnecessary, if not irrelevant.

PMID- 8531846
TI  - Optic nerve head infiltration in acute leukemia in children: an indication for
      emergency optic nerve radiation therapy.
AB  - Two pediatric patients with acute leukemia who developed optic nerve head
      leukemic infiltration are presented. In one patient both eyes were involved at
      diagnosis as well as her central nervous system. Despite systemic and intrathecal
      chemotherapy she lost her vision within a few weeks. Cranial irradiation at that
      point could not reverse this outcome. In the second patient optic nerve head
      infiltration was found a few months after diagnosis, treated promptly with
      cranial irradiation and her vision was saved. Her central nervous system (CNS)
      was not involved at any time. It is stressed that ocular complaints including eye
      pain or blurred vision in the pediatric patient with leukemia should be
      investigated without delay by an ophthalmologist. In the young child these
      complaints may be absent and change in the visual behavior should then alert the
      pediatric oncologist for possible ocular problems. If optic nerve head leukemic
      infiltration is diagnosed and promptly treated with emergency radiation, vision
      can be salvaged.

PMID- 8531847
TI  - Successful desensitization to carboplatin in patients with systemic
      hypersensitivity reactions.
AB  - Carboplatin is the drug of choice for the treatment of nonresectable astrocytomas
      in children, but patients who are intolerant may require cranial irradiation
      which is associated with significant morbidity. Hypersensitivity reactions,
      including urticaria, bronchospasm, and hypotension, have been reported in 1% to
      30% of patients treated with carboplatin. Although a few patients have attempted
      to continue therapy following pretreatment with antihistamines and
      corticosteroids, most have had recurrent severe reactions and have discontinued
      therapy. Two children with a history of severe systemic reactions to carboplatin
      were pretreated with 1 to 2 mg/kg of oral prednisolone the night before and the
      morning of their infusion. The initial desensitization was carried out in the
      intensive care unit (ICU) using doses of 1, 2.5, 5, 10, 25, and 50 mg of
      carboplatin infused at 1 mg/min every 15 minutes. This was well-tolerated and the
      remainder of the dose was infused at the standard rate of 200 mg/hr. One patient
      continued to receive infusions in the clinic without any difficulty. The other
      patient tolerated a second infusion, but during his third he experienced a
      systemic reaction that required discontinuation of the infusion and treatment
      with diphenhydramine. Desensitization was repeated in the ICU with pretreatment
      with prednisolone, diphenhydramine, and ranitidine, starting with 0.1 mg of
      carboplatin, and increasing more slowly than in the first protocol. This was well
      tolerated, and subsequent infusions have been administered beginning with 1 mg
      doses without adverse effects. Both boys continued therapy with carboplatin;
      their astrocytomas are stable and they are clinically well. The use of the
      desensitization protocol enabled them to avoid cranial irradiation and improved
      their chances for normal neurologic development.

PMID- 8531848
TI  - Solitary focal demyelination in the brain as a paraneoplastic disorder.
AB  - Solitary focal demyelination (SFD) in the brain is an uncommon and poorly
      understood disorder of uncertain etiology that may represent an intermediate
      entity between multiple sclerosis and acute disseminated encephalomyelitis. In a
      few reported cases of SFD, the patient was briefly noted to have a
      nonneurological malignancy. We studied two patients who had solitary focal
      lesions in the brain. Utilizing magnetic resonance imaging and tissue biopsy, we
      found the characteristics of the brain lesions in these two patients to be those
      of SFD. In our combined experience over the past 10 years, we have encountered no
      similar brain lesions at our medical center. We found it remarkable that both of
      these patients also had malignancy outside of the nervous system. One had a
      seminoma, and the other a lymphoma. We conclude that some cases of SFD in the
      brain may occur as a paraneoplastic disorder associated with nonneurological
      malignancies.

PMID- 8531849
TI  - Multiple central nervous system haemangioblastomas.

PMID- 8531850
TI  - Bone marrow micrometastases in a patient with localized Wilms' tumor.
AB  - The case of a 7-year-old boy presenting at diagnosis with a localized (stage III)
      Wilms' tumor of favorable histology is presented. Immunocytologic analysis of
      bone marrow aspirates revealed cells positive for neural cell adhesion molecule
      (NCAM) and negative for class I major histocompatibility complex (MHC) antigens.
      These cells were interpreted as deriving from the tumor blastemal component.
      Postoperatively the child underwent radiotherapy and chemotherapy, and he remains
      free of disease 12 months after completion of therapy. In patients with
      nonmetastatic Wilms' tumor at onset, the evaluation of the actual frequency of
      occult marrow involvement and the assessment of its clinical significance may
      necessitate further investigation.

PMID- 8531851
TI  - Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central
      nervous system mass lesion 9 years after initial diagnosis.
AB  - Seven years after completion of chemotherapy for acute lymphoblastic leukemia,
      diagnosed at the age of 5 years, a black female presented with signs of increased
      intracranial pressure. Neuroimaging showed a large enhancing extra-axial
      occipital tumor mass. The resection specimen showed morphologic, cytogenetic, and
      immunophenotypic features consistent with relapse of the primary leukemia. Bone
      marrow examination was negative for malignancy. The long duration of complete
      remission followed by the formation of a mass in the central nervous system are
      highly unusual features of recurrent acute lymphoblastic leukemia.

PMID- 8531852
TI  - Massive gastrointestinal hemorrhage from AIDS-related Kaposi's sarcoma confined
      to the small bowel managed with radiation.
AB  - A > 50% incidence of Kaposi's sarcoma (KS) of the gastrointestinal tract has been
      seen in acquired immunodeficiency syndrome (AIDS) patients with cutaneous KS.
      Although gastrointestinal Kaposi's sarcoma (GIKS) is usually asymptomatic,
      hemorrhages from the oral cavity, esophagus, stomach, and large bowel have
      occurred in this disease. We describe a patient with acute, massive
      gastrointestinal hemorrhage from GIKS confined to the small bowel who was treated
      with chemotherapy, surgery, and radiation. To the best of our knowledge, this is
      the first reported case of AIDS-related GIKS limited to the small bowel. Although
      chemotherapy is generally used successfully to palliate diffuse GIKS, we report
      that radiation was an effective modality that rapidly resulted in resolution of
      considerable local bleeding and could be used in such cases as an alternative to
      surgery. Details of this case history, including radiographs, are presented.

PMID- 8531853
TI  - Mesenchymal chondrosarcoma of the foot, an unusual location: case report and
      review of the literature.
AB  - We present a case of primary mesenchymal chondrosarcoma of the proximal phalanx
      of the first toe. The bones of the foot represent an infrequent primary site for
      this neoplasm. The tumour consisted of layers of undifferentiated round cells
      with scanty cytoplasm and hyperchromatic nuclei. The presence of brain, lung, and
      left auricle metastasis was demonstrated, and the patient died due to brain edema
      18 days after admission. Mesenchymal chondrosarcoma is a rare tumor that more
      frequently involves the pelvic bones, the femur, and the humerus. To our
      knowledge, only nine cases of primary mesenchymal chondrosarcoma arising from the
      bones of the foot have been previously reported, with none involving the phalanx
      of the toe.

PMID- 8531854
TI  - Is the deletion of the short arm of chromosome 1 a prognostic factor in pediatric
      peripheral primitive neuroepithelioma (PNET)?

PMID- 8531855
TI  - The new SIOP (Stockholm) working classification of renal tumours of childhood.
      International Society of Paediatric Oncology.

PMID- 8531856
TI  - Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor
      Study Group.
AB  - This report defines the incidence and determines the etiology of renal failure
      (RF) in patients undergoing treatment for Wilms' tumor (WT). The database of the
      National Wilms' Tumor Study (NWTS) was searched to identify all children reported
      to have developed chronic renal failure. There were 55 patients found to have RF.
      Of these, 39 patients had bilateral tumors, 15 with unilateral disease and one
      with a WT in a solitary kidney. The median interval from diagnosis to the onset
      of renal failure was 21 months. The incidence of RF in bilateral WT was 16.4% for
      NWTS-1 & -2, 9.9% for NWTS-3, and 3.8% for NWTS-4. The incidence of RF in
      unilateral WT remained stable. The most common etiologies of RF were: bilateral
      nephrectomy for persistent or recurrent tumor (24 pts), Drash syndrome (12 pts),
      progressive tumor in the remaining kidney (5 pts), radiation nephritis (6 pts),
      and other causes (5 pts). The etiology of renal failure was not reported in three
      children. Children with unilateral WT and a normal contralateral kidney have a
      very low incidence of RF, and this review does not support a recommendation for
      parenchymal sparing procedures in these patients. Children with bilateral WT are
      at risk for the development of RF, and parenchymal sparing procedures are
      warranted.

PMID- 8531857
TI  - Alveolar soft part sarcoma in children and adolescents: clinical features and
      outcome of 11 patients.
AB  - The clinical features and response to therapy of pediatric alveolar soft part
      sarcoma, a rare soft tissue sarcoma of uncertain histogenesis, have not been
      previously described in detail in the literature. We retrospectively reviewed the
      clinical characteristics of all patients with alveolar soft part sarcoma who were
      seen at our institution over a 32-year period. We found 11 patients with the
      diagnosis of alveolar soft part sarcoma. Their ages ranged from 2.8-16 years
      (median 9.8). Staging was determined using the Intergroup Rhabdomyosarcoma Study
      clinical grouping system and the UICC TNM system. Accordingly, there were six
      patients with grossly resected tumors (clinical groups I and II) and five with
      unresected or metastatic disease (clinical groups III and IV). Children with
      resected disease were more likely to have smaller noninvasive tumors. The main
      feature predictive of survival was tumor resectability, since chemotherapy in
      various combinations failed to produce significant tumor responses. Nine patients
      are disease-free with a median follow-up of 11.9 years. Surgical resection
      remains the mainstay of therapy for pediatric alveolar soft part sarcoma. Since
      active chemotherapy agents have not been identified, patients with unresected or
      metastatic disease may benefit from experimental agents. The survival rate of
      this cohort is superior to that seen in adults.

PMID- 8531858
TI  - Hepatotoxicity of 6-mercaptopurine in childhood acute lymphocytic leukemia:
      pharmacokinetic characteristics.
AB  - Treatment with 6-mercaptopurine (6MP) is associated with adverse gastrointestinal
      (GI) and hepatic effects. Four patients, ages 6.9 +/- 2.6 (mean +/- S.D.) years,
      with acute lymphocytic leukemia (ALL) on maintenance chemotherapy including 6MP,
      developed nausea, vomiting, abdominal pain, elevated liver enzymes, and
      hyperbilirubinemia after 1.4 +/- 1.0 (range 0.5-2) years. Liver biopsy in 1
      patient was suggestive of drug-induced intrahepatic cholestatis. Symptoms
      resolved and liver function returned to normal after discontinuation of 6MP.
      Pharmacokinetic data of the symptomatic patients were compared with those of 25
      ALL patients on the same protocol but without GI symptoms or hepatotoxicity.
      Levels of 6-thioguanine nucleotides (6-TGN) and the methylated metabolites of 6MP
      in red blood cells of the patients with hepatotoxicity, were not significantly
      different when compared to patients without hepatotoxicity, suggesting similar
      absorption of 6MP in both groups. Time to achieve peak 6MP levels was
      significantly longer in the symptomatic patients compared to the asymptomatic
      patients (P = 0.005). Peak levels and standardized concentration versus time
      curve (AUC) per 1 mg of 6MP per m2 of body surface area were significantly lower
      in the patients with hepatotoxicity (P = 0.016; P = 0.037, respectively). A
      significant correlation between peak 6MP levels and standardized AUC (r = 0.729,
      P < 0.0001) was found. These results suggest accumulation of 6MP and its
      metabolites in the liver of the patients with GI symptoms, leading to
      hepatotoxicity.

PMID- 8531859
TI  - Childhood Hodgkin's disease in Campinas, Brazil.
AB  - PURPOSE: Little clinical information about Hodgkin's disease in children is
      available from poor countries. The object of this study is to evaluate our data
      in Campinas, Brazil and hope "to make one dot on the geographic map of this
      disease more clear." PATIENTS AND METHODS: Between 1978 and 1988, 46 patients
      under the age of 17 years with biopsy-proven Hodgkin's Disease (HD) were referred
      for evaluation at Centro Boldrini in Campinas, Sao Paulo state, in Brazil. Thirty
      seven of them were treated and followed-up only at this Center and are the
      subjects of this analysis. All the original histological slides were obtained,
      reviewed, and classified according to the Rye system. Staging procedures included
      exploratory laparotomy in 33 of 37 children, but none had lymphangiography.
      Treatment was individualized until January 1986 when the German protocol was
      adopted. RESULTS: Nineteen cases were classified as nodular sclerosis, 14 as
      mixed cellularity, and three as lymphocyte depleted. Mean age was 7 years;
      male/female ratio was 2:1. Fifty percent were advanced stages III and IV and 46%
      (17/37) had at least one of the systemic B symptoms. Mean follow-up was 81 months
      (range from 41 to 174 months). Five-year actuarial overall survival was 78%. Two
      children (5%) had acute myeloid leukemia at 25 and 49 months after diagnosis.
      CONCLUSIONS: Although distribution of histological subtypes of our cases is
      similar to other reports in developed countries, as well as percentage of
      advanced stages III/IV, our patients fared worse when compared to those reports.
      The reason for this continues to remain unclear but it does not seem to be
      related to histology subtypes.

PMID- 8531860
TI  - Hearing loss in children with brain tumors treated with cisplatin and carboplatin
      based high-dose chemotherapy with autologous bone marrow rescue.
AB  - Carboplatin is less ototoxic than cisplatin, but ototoxicity may occur with
      carboplatin at higher doses. We evaluated hearing in children with brain tumors
      treated with conventional dose cisplatin followed by high-dose carboplatin.
      Children under 6 years of age, newly diagnosed with brain tumors, were treated
      after surgery with cisplatin, Etoposide, cyclophosphamide, and vincristine,
      followed by consolidation with carboplatin, ThioTEPA, Etoposide, and autologous
      bone marrow rescue. Hearing was assessed before and after consolidation,
      utilizing standard audiometric techniques. Seven of the 11 evaluable patients
      developed high-frequency sensorineural hearing loss after induction therapy.
      Hearing deteriorated after consolidation in five patients, with pure tone
      threshold shifts of up to 65 dB between 2,000 and 8,000 Hz. Of these five
      patients, audiological abnormalities were documented in four prior to
      consolidation, one received cranial irradiation after consolidation, and all five
      received aminoglycoside antibiotics for at least 2 weeks, with toxic drug levels
      in four. Three patients have subsequently required hearing aids. Significant
      ototoxicity is common in these patients. Ototoxicity related to consolidation
      therapy is likely due to the high dose of carboplatin used, prior cisplatin
      therapy, aminoglycosides, and, in one patient, cranial irradiation. Audiological
      assessment is essential in children treated with dose-intensive chemotherapy
      regimens containing cisplatin and carboplatin for identification and
      rehabilitation of ototoxicity.

PMID- 8531861
TI  - The relaxation of supercoiled DNA molecules as a biophysical dosimeter for
      ionizing radiations: a feasibility study.
AB  - In this paper we explore the feasibility of using DNA molecules as a biophysical
      radiation dosimeter. Supercoiled phi X174 bacteriophage DNA molecules were
      irradiated with different gamma radiation doses. The strand breakage produced by
      ionizing radiation within supercoiled double-stranded DNA molecules (RFI) yields
      relaxed circular DNA molecules (RFII) and linear DNA molecules (RFIII) as a
      result of single-strand breaks and double-strand breaks, respectively. The
      irradiated samples were subjected to electrophoresis on agarose gels to separate
      the three forms. A proprietary fluorescent dye was used to detect DNA bands
      within the gel, which was photographed under UV transillumination. The negative
      was scanned with a computerized imaging densitometric system for DNA band
      quantitation. The relative fractions of the three molecular forms are dose
      dependent, and can be modeled mathematically with five parameters. The values of
      the parameters were determined by optimizing the fit of the model to the data,
      using a nonlinear regression procedure of a commercial statistical analysis
      package. Once the parameters of DNA breakage have been determined, absorbed dose
      can be measured by this technique, which we have termed supercoil relaxation
      dosimetry. The average accuracy of dose determination for our system over the
      range of 1-40 Gy was about 5%. Supercoil relaxation dosimetry may be well suited
      to certain difficult dosimetric problems.

PMID- 8531862
TI  - Influence of shape on the accuracy of grid-based volume computations.
AB  - The influence of the shape of a region of interest (ROI) on the uncertainty in
      the sampled volume of the ROI is investigated for computations with regular
      Cartesian grids. Both mathematically defined volumes and clinically relevant ROIs
      were studied. The sampling uncertainty is shown to depend on the compactness of
      the ROI and on effects of grid matching and translational symmetry. In clinical
      ROIs without translational symmetry the estimate of the sampling uncertainty is
      improved up to a factor of 2.3 by taking the compactness of the ROI into account.
      In a spherical ROI grid-matching effects were demonstrated by means of Fourier
      transforms. In this type of ROI, grid-matching effects decrease as well as
      increase the sampling uncertainty up to a factor of 1.6. Translational symmetry
      is shown to cause a decrease in the sampling uncertainty convergence power from
      2/3 for spherical ROIs, to 1/2 for stringlike or 1/3 for pancakelike cylinders.
      For clinical ROIs with translational symmetry, similar decreases were found. With
      the theory derived and these symmetry effects taken into account the experimental
      uncertainty of volume computation can be estimated for most clinical ROIs within
      a factor of 2.5. Special care should be taken in grid sampling of volumes inside
      isodose surfaces of rectangular field techniques. For the volume of a prostate an
      uncertainty level of 1% or 5% is obtained with less than 1050 or 80 grid points,
      respectively, while for such an isodose surface up to 16,000 or 500 grid points
      are required for the same uncertainty levels.

PMID- 8531864
TI  - Measurement of a photon penumbra-generating kernel for a convolution-adapted
      ratio-TAR algorithm for 3D treatment planning.
AB  - A method has been developed to measure a photon penumbra-generating kernel using
      dosimetry equipment available in most radiation therapy departments. The kernel
      is used in a convolution-adapted ratio-TAR algorithm in our three-dimensional
      treatment planning system. The kernel is assumed to be invariant with respect to
      off-axis position, axially symmetric, and is divided into short- and long-range
      components, with a different measurement technique for each. The data required to
      obtain the short-range component are measured by scanning across a split-field
      geometry incident on a water phantom. The derivative of the measured profile is
      proportional to one-dimensional projections across the kernel. Because the kernel
      is axially symmetric, only one profile measurement is required for each depth. A
      CT reconstruction technique is used to extract the radial dependence of the
      kernel from the strip integrals. Electronic noise in the acquisition system
      yields significant uncertainties in the kernel shape for distances beyond 3 cm.
      The long-range portion of the kernel is obtained by examining tissue-air ratios
      (TARs). The derivative of the TAR at the center of a circular field is
      proportional to the kernel value at the distance corresponding to the radius of
      the field. The kernel measurement method was tested by comparing measured and
      calculated square-field profiles at a variety of depths. Agreement was within 1%
      within the field boundary and 3% outside the field boundary for all depths.

PMID- 8531863
TI  - A Monte Carlo model of photon beams used in radiation therapy.
AB  - A generic Monte Carlo model of a photon therapy machine is described. The model,
      known as McRad, is based on EGS4 and has been in use since 1991. Its primary
      function has been the characterization of the incident photon fluence for use by
      dose calculation algorithms. The accuracy of McRad is examined by comparing the
      dose distributions in a water phantom generated using only the Monte Carlo data
      with measured dose distributions for two machines in our clinic; a 6 MV Varian
      Clinac 600C and the 15 MV beam from a Clinac 2100C. The Monte Carlo generated
      dose distributions are computed using a dose calculation algorithm based on the
      use of differential pencil beam kernels. It was found that the match to measured
      data could be improved if the model is tuned by adjusting the energy of the
      electron beam incident on the target. The beam profiles were found to be more
      sensitive indicators of the electron beam energy than the depth dose curves.
      Beyond the depths reached by contaminant electrons, the computed and measured
      depth dose curves agree to better than 1%. The comparison of beam profiles
      indicate that in regions up to within 1 cm of the field edge, the measured and
      computed doses generally agree to within 2%-3%.

PMID- 8531865
TI  - Noise reduction by frame averaging: a numerical simulation for portal imaging
      systems.
AB  - We have studied the usefulness of both pre- and post-ADC frame summing for the
      purpose of reducing the effect of quantum noise and digitization noise in portal
      imaging systems. The study is based on the fluorescent-screen video-camera type
      of system. The study predicts the not-surprising result that provided the noise
      level at the ADC input is sufficiently large, the overall SNR can be increased by
      a factor of square root of M1M2, where M1 and M2 are the number of frames summed
      before and after the ADC. The study also predicts, somewhat unexpectedly, that
      there is an operating region in which increasing M1 actually decreases the SNR in
      the final image. To avoid this region M1 must be less than approximately 6 x
      2(2B) (1 + -delta-1)1/2/(iaccf), where B is the number of ADC bits, -delta is the
      mean number of optical photons detected by the video camera per detected x-ray
      photon, iacc is the open-field number of detected x-ray photons per accelerator
      pulse per pixel, and f is the patient transmission factor. An equivalent
      statement is that the rms noise at the input to the ADC, sigma in, must exceed
      approximately 0.4q where q is the quantization interval of the ADC. It is
      possible that some systems operate in or close to this region. A second feature
      of this anomalous behavior is that the final image is not necessarily improved by
      increasing the number M2 of post-ADC-summed frames. For example, when sigma in/q
      = 0.2, there is no improvement in the overall rms error for M2 > 32.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8531866
TI  - Accounting for primary electron scatter in x-ray beam convolution calculations.
AB  - Fermi-Eyges electron-scattering theory has been incorporated into the primary
      dose calculation for external x-ray beam radiotherapy using the convolution
      method. Incorporating scattering theory into the convolution technique accounts
      for the density distribution between the interaction and deposition sites,
      whereas conventional convolution methods only consider the average density
      between these two points. As the lateral spread of electrons ejected from an
      interaction site depends on the density distribution, the energy deposition (and
      hence dose distribution) is predicted more accurately if scattering is accounted
      for. This new method gives depth dose curves which show better agreement with
      Monte Carlo calculations in a (slab inhomogeneity) lung phantom than a
      conventional convolution method, especially at high energies and small field
      sizes where lateral electronic disequilibrium exists at the central axis. For a 5
      x 5-cm2 18-MV beam incident on the lung phantom, a reduction in the maximum error
      between the convolution and Monte Carlo depth dose curves from 5% to 2.5% is
      obtained when scattering theory is used in the primary dose calculation.
      Incorporating scattering theory into the convolution calculation increases the
      computation time of the primary dose by a factor of 3.

PMID- 8531867
TI  - A model for electron-beam applicator scatter.
AB  - Applicators (or cones), used in conjunction with patient specific cutouts in
      electron-beam radiotherapy, may interact with the primary electron beam to
      produce a secondary beam component (applicator scatter). This component affects
      machine output as well as the shape of resulting dose distributions. A model has
      been developed to simulate this scatter component for applicators consisting of
      trimming plates of arbitrary shape. This model involves sampling established
      kernels of scatter from edge elements of appropriate materials, obtained through
      Monte Carlo simulations. The result of the model is a phase space (position,
      direction, energy, charge, weighting) of applicator scattered particles which can
      be incorporated into a further Monte Carlo simulation, or as input into another
      advanced treatment planning algorithm. This model is evaluated by comparison of
      measured profiles and applicator scatter component depth dose curves with Monte
      Carlo simulations using simulated phase-space data as input. Results are very
      consistent and reveal information on the angular and spatial variation
      characteristics of this beam component. The results obtained verify the developed
      model as an accurate predictor of the characteristics of applicator scattered
      particles.

PMID- 8531868
TI  - A Monte Carlo investigation of electron-beam applicator scatter.
AB  - An EGS4 Monte Carlo investigation into applicator scatter in clinical electron
      beams has been undertaken in order to establish the characteristics of electrons
      incident on the patient surface which have interacted with collimation systems.
      The applicator scattered component of an electron beam (including that from
      irregularly shaped cutouts) should be considered when modeling the electron phase
      space since it represents a component of the beam incident on the patient with
      widely varying characteristics to those of the primary beam. Scattering off an
      edge of applicator material is considered in terms of the types and
      characteristics of incident primary beam, the resulting interactions in the edge,
      and the fluence and energy characteristics of the emerging particles. Results
      indicate that the principal component to consider is scattered electrons due to
      the electron component of the primary beam, and that the fluence and energy
      characteristics of this component are dependent upon primary beam energy and the
      configuration of the applicator apertures.

PMID- 8531869
TI  - Geometric gradient--a new estimation of the surface normal for three-dimensional
      medical imaging.

PMID- 8531870
TI  - Comment on "Optimization of pencil beam widths for electron-beam dose
      calculations" [Med. Phys. 22, 411-419 (1995)].

PMID- 8531871
TI  - The nonlinear partial volume effect and computed tomography densitometry of foam
      and lung.
AB  - A quantitative study was performed to assess the magnitude of the nonlinear
      partial volume effect (NLPVE) in computed tomography (CT) densitometry of
      polyethene foam and lung. This effect arises in materials having density
      variations on the scale of the sampling area of an individual CT-detector
      element. It causes a systematic underestimation of the density determined with
      CT. Foam samples and a resected lung of a goat were imaged with high resolution
      (20 lp/mm) using a mammography system, and the observed optical density variation
      in the images was converted into a distribution of pathlengths that x rays
      penetrate within the solid component of the cellular material. The obtained
      pathlength distribution was used to calculate the transmission, as seen by a
      single detector in computed tomography. Comparison with the transmission through
      homogeneous material of the same thickness gave an estimate of the NLPVE. For the
      foams studied, the CT-determined density was found to be too low by approximately
      0.3%-0.5% due to this effect. Although these density errors are small, in
      calibrations of a CT scanner they may be of significance. For lung the
      underestimation of the density was less than 0.1%. These experimentally derived,
      NLPVE related CT-density errors are 32%-84% of those calculated from a simple
      model of a cellular solid.

PMID- 8531872
TI  - Calculation of dose in asymmetric photon fields.
AB  - A method is introduced to calculate monitor units to points off axis. Extensive
      data are presented comparing this method with measured values of dose per monitor
      unit on the central ray of asymmetric fields produced by a variety of linear
      accelerators. The technique demonstrates improvement over existing methods that
      use large-field profile data. The method is found to be both simple and accurate:
      Agreement within +/- 2% is obtained using parameters readily available within the
      clinic.

PMID- 8531873
TI  - Physical characteristics of a clinical d(48.5)+Be neutron therapy beam produced
      by a superconducting cyclotron.
AB  - The Harper Hospital and Wayne State University fast neutron therapy facility is
      the only one in the world to use a compact superconducting cyclotron and multirod
      collimator. Neutrons are produced by the interaction of the 48.5-MeV deuteron
      beam with a thick internal beryllium target and the compact accelerator is gantry
      mounted to allow full 360 degrees rotation of the neutron beam about the therapy
      couch. The deuteron beam strikes the beryllium target at a glancing angle. A
      flattening filter is used to flatten the asymmetric neutron beam which results
      from this geometry. Details of the flattening filter design and construction are
      discussed. The physical characteristics of the resulting neutron therapy beam
      were measured. The central axis depth-dose values are approximately equivalent to
      those of a 4-MV photon beam. The dose buildup curve reaches its maximum value at
      a depth of 9 mm in a water phantom and the surface dose is approximately 42%. The
      beam penumbra produced by the multirod collimator has been measured in terms of
      the distance between the 20% and 80% isodose lines. The penumbra width for a 10 x
      10-cm2 field at a depth of 10 cm in a water phantom is 1.65 +/- 0.1 cm, and is
      comparable to that achieved with other high-energy neutron beams. The long-term
      stability of the dose monitoring system has been measured and found to be
      satisfactory. The physical characteristics of the neutron beam are comparable
      with those of other modern fast neutron therapy facilities.

PMID- 8531874
TI  - A simple method of obtaining off-axis half-value layers for megavoltage photon
      beams.
AB  - We describe a simplified technique for the acquisition of off-axis beam-quality
      data (i.e., half-value layers in water) for medical linear accelerators. A
      measurement protocol is presented in which an ordinary beam-scanning water
      phantom is used to accurately position an ionization chamber at appropriate
      measuring positions. Attenuation coefficients are calculated by performing a
      regression on the measured data. The technique uses the smallest fields for which
      lateral electron equilibrium can be established.

PMID- 8531875
TI  - Considerations for superficial photon dosimetry.
AB  - Dose measurements at superficial energies required special considerations. First,
      care must be taken in selecting appropriate phantom materials. Materials that are
      adequate tissue substitutes at megavoltage energies might not be adequate at
      superficial energies. The suitability of a material can be judged by comparing
      its mass attenuation and mass energy absorption coefficients at superficial
      energies to those of the tissue of interest. Second, very low energy x-ray and
      electron contaminants must be removed from the superficial beam before they reach
      the detector. For detectors with a very thin window, this can be achieved by
      placing thin film on top of the detector. Failure to properly eliminate
      contaminants can result in a large increase in dose measured directly at the
      surface.

PMID- 8531876
TI  - Comment on "Intercomparison on normalized head-scatter factor measurement
      techniques" [Med. Phys. 22, 249-253 (1995)].

PMID- 8531877
TI  - Comments on "Intercomparison of normalized head-scatter factor measurement
      techniques" [Med. Phys. 22, 249-253 (1995)].

PMID- 8531878
TI  - The evaluation of optimized implants for idealized implant geometries.
AB  - The purpose of this paper is to investigate the utility of implant quality
      measures on single stepping-source brachytherapy treatment plans. Four dwell
      weight optimization algorithms were applied to four regular geometric implants:
      single plane, double plane, cuboid, and cylindrical. The dwell weight
      optimization schemes included equal weighing, two commercial optimization schemes
      (dose-point and geometric) and a variation of the Paterson-Parker distribution
      rules. The implant quality measures were investigated as a function of dose-per
      integrated reference air kerma (IRAK) to eliminate bias resulting from a
      prescription choice. A particular dose per IRAK refers to a dose surface that is
      a function only of the relative dwell weight distribution and is therefore well
      suited to investigate dwell weight optimization schemes. The implant quality
      measures included the dose-nonuniformity ratio (DNR) developed by Saw and a
      coverage index to assess the isodose coverage relative to the implanted volume.
      These were termed direct quantities due to their clear clinical significance.
      Additional measures include the ratio of the implant dose-volume histogram (DVH)
      to that of a point source exhibiting the same IRAK (Rp) and the ratio of the
      optimized DVH to the equally weighted DVH (EWR). The widths of the Rp curves and
      depths of the EWR curves were used to characterize these indirect implant quality
      measures. To evaluate the effectiveness of both the direct and indirect measures,
      they were correlated with the DNR for an isodose surface that covered the implant
      (D0). The efficiency of the dwell weight distribution was examined by noting the
      dose-per-IRAK surface D0.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8531879
TI  - Comparison of NIST and manufacturer calibrations of 90Sr+90Y ophthalmic
      applicators.
AB  - Since the resumption of the NIST calibration service for 90Sr+90Y beta-particle
      ophthalmic applicators, 65 sources have been calibrated using the revised
      technique [C. G. Soares, Med. Phys. 18, 787-793 (1991)]. For 59 of these sources,
      the manufacturer's calibration results were available for comparison to the NIST
      calibration results. The 59 sources represent eight different manufacturers, only
      one of which is still selling new sources. Manufacturer calibration dates range
      from the present back to 1954. The results of the comparisons are present, broken
      down by both manufacturer and calibration date; there are interesting and
      significant trends in both, with average differences of 20% not uncommon. The
      obsolete unit, "roentgen-equivalent-beta" (reb), in which some of the
      manufacturer calibrations are expressed, is discussed, and a factor (0.00982 Gy
      reb-1) for its conversion to absorbed dose is suggested.

PMID- 8531880
TI  - Verification of manufacturer-supplied 125I and 103Pd air-kerma strengths.

PMID- 8531881
TI  - A method to check treatment time calculations in Ir-192 high-dose-rate volume
      implants.

PMID- 8531882
TI  - Classification of mass and normal breast tissue on digital mammograms:
      multiresolution texture analysis.
AB  - We investigated the feasibility of using multiresolution texture analysis for
      differentiation of masses from normal breast tissue on mammograms. The wavelet
      transform was used to decompose regions of interest (ROIs) on digitized
      mammograms into several scales. Multiresolution texture features were calculated
      from the spatial gray level dependence matrices of (1) the original images at
      variable distances between the pixel pairs, (2) the wavelet coefficients at
      different scales, and (3) the wavelet coefficients up to certain scale and then
      at variable distances between the pixel pairs. In this study, 168 ROIs containing
      biopsy-proven masses and 504 ROIs containing normal parenchyma were used as the
      data set. The mass ROIs were randomly and equally divided into training and test
      groups along with corresponding normal ROIs from the same film. Stepwise linear
      discriminant analysis was used to select optimal features from the
      multiresolution texture feature space to maximize the separation of mass and
      normal tissue for all ROIs. We found that texture features at large pixel
      distances are important for the classification task. The wavelet transform can
      effectively condense the image information into its coefficients. With texture
      features based on the wavelet coefficients and variable distances, the area Az
      under the receiver operating characteristic curve reached 0.89 and 0.86 for the
      training and test groups, respectively. The results demonstrate that a linear
      discriminant classifier using the multiresolution texture features can
      effectively classify masses from normal tissue on mammograms.

PMID- 8531883
TI  - Computer-aided diagnosis for interstitial infiltrates in chest radiographs:
      optical-density dependence of texture measures.
AB  - We have been developing a computerized scheme for automated detection and
      characterization of interstitial infiltrates based on the Fourier transform of
      lung texture. To improve the performance of the scheme, which was developed using
      digitized screen-film radiographs, optical-density dependence of both the
      gradient of the film used and the system noise associated with the laser scanner
      were investigated. Two hundred chest radiographs, including 100 abnormal cases
      with interstitial infiltrates, were digitized using a laser scanner. The root
      mean-square (RMS) variations and the first moments of the power spectra, which
      correspond to the magnitude and coarseness of lung texture, were determined by
      Fourier transform of lung textures in numerous regions of interest (ROIs). The
      RMS variation was dependent upon the average optical density in the ROI, though
      no obvious trend existed for the first moment of the power spectrum. Dependence
      of the RMS variations on optical density was corrected for using the gradient
      curve of the film. Also, system noise associated with the laser scanner was
      corrected. Results indicated that the specificity was improved from 81% (without
      correction) to 89% (with corrections), without any loss of sensitivity (90%).
      Thus, the correspondence between the computer output and consensus interpretation
      of radiologists was improved with the new scheme compared to the previous one.
      This improved computerized scheme may be useful to radiologists in detecting
      interstitial infiltrates in chest radiographs.

PMID- 8531884
TI  - Role of nitric oxide in parasitic infections.
AB  - Nitric oxide is produced by a number of different cell types in response to
      cytokine stimulation and thus has been found to play a role in immunologically
      mediated protection against a growing list of protozoan and helminth parasites in
      vitro and in animal models. The biochemical basis of its effects on the parasite
      targets appears to involve primarily inactivation of enzymes crucial to energy
      metabolism and growth, although it has other biologic activities as well. NO is
      produced not only by macrophages and macrophage-like cells commonly associated
      with the effector arm of cell-mediated immune reactivity but also by cells
      commonly considered to lie outside the immunologic network, such as hepatocytes
      and endothelial cells, which are intimately involved in the life cycle of a
      number of parasites. NO production is stimulated by gamma interferon in
      combination with tumor necrosis factor alpha or other secondary activation
      signals and is regulated by a number of cytokines (especially interleukin-4,
      interleukin-10, and transforming growth factor beta) and other mediators, as well
      as through its own inherent inhibitory activity. The potential for design of
      prevention and/or intervention approaches against parasitic infection (e.g.,
      vaccination or combination chemo- and immunotherapy strategies) on the basis of
      induction of cell-mediated immunity and NO production appears to be great, but
      the possible pathogenic consequences of overproduction of NO must be taken into
      account. Moreover, more research on the role and regulation of NO in human
      parasitic infection is needed before its possible clinical relevance can be
      determined.

PMID- 8531886
TI  - Conjugative transposons: an unusual and diverse set of integrated gene transfer
      elements.
AB  - Conjugative transposons are integrated DNA elements that excise themselves to
      form a covalently closed circular intermediate. This circular intermediate can
      either reintegrate in the same cell (intracellular transposition) or transfer by
      conjugation to a recipient and integrate into the recipient's genome
      (intercellular transposition). Conjugative transposons were first found in gram
      positive cocci but are now known to be present in a variety of gram-positive and
      gram-negative bacteria also. Conjugative transposons have a surprisingly broad
      host range, and they probably contribute as much as plasmids to the spread of
      antibiotic resistance genes in some genera of disease-causing bacteria.
      Resistance genes need not be carried on the conjugative transposon to be
      transferred. Many conjugative transposons can mobilize coresident plasmids, and
      the Bacteroides conjugative transposons can even excise and mobilize unlinked
      integrated elements. The Bacteroides conjugative transposons are also unusual in
      that their transfer activities are regulated by tetracycline via a complex
      regulatory network.

PMID- 8531885
TI  - Genetic elements of plant viruses as tools for genetic engineering.
AB  - Viruses have developed successful strategies for propagation at the expense of
      their host cells. Efficient gene expression, genome multiplication, and invasion
      of the host are enabled by virus-encoded genetic elements, many of which are well
      characterized. Sequences derived from plant DNA and RNA viruses can be used to
      control expression of other genes in vivo. The main groups of plant virus genetic
      elements useful in genetic engineering are reviewed, including the signals for
      DNA-dependent and RNA-dependent RNA synthesis, sequences on the virus mRNAs that
      enable translational control, and sequences that control processing and
      intracellular sorting of virus proteins. Use of plant viruses as extrachromosomal
      expression vectors is also discussed, along with the issue of their stability.

PMID- 8531887
TI  - Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines.
AB  - Although pneumococcal conjugate vaccines are close to being licensed, a more
      profound knowledge of the virulence factors responsible for the morbidity and
      mortality caused by Streptococcus pneumoniae is necessary. This review deals with
      the major structures of pneumococci involved in the pathogenesis of pneumococcal
      disease and their interference with the defense mechanisms of the host. It is
      well known that protection against S. pneumoniae is the result of phagocytosis of
      invading pathogens. For this process, complement and anticapsular polysaccharide
      antibodies are required. Besides, relatively recent experimental data suggest
      that protection is also mediated by the removal of disintegrating pneumococci and
      their degradation products (cell wall, pneumolysin). These structures seem to be
      major contributors to illness and death caused by pneumococci. An effective
      conjugate vaccine should therefore preferably include the capsular polysaccharide
      and at least one of these inflammatory factors.

PMID- 8531888
TI  - Nitrogen control in bacteria.
AB  - Nitrogen metabolism in prokaryotes involves the coordinated expression of a large
      number of enzymes concerned with both utilization of extracellular nitrogen
      sources and intracellular biosynthesis of nitrogen-containing compounds. The
      control of this expression is determined by the availability of fixed nitrogen to
      the cell and is effected by complex regulatory networks involving regulation at
      both the transcriptional and posttranslational levels. While the most detailed
      studies to date have been carried out with enteric bacteria, there is a
      considerable body of evidence to show that the nitrogen regulation (ntr) systems
      described in the enterics extend to many other genera. Furthermore, as the range
      of bacteria in which the phenomenon of nitrogen control is examined is being
      extended, new regulatory mechanisms are also being discovered. In this review, we
      have attempted to summarize recent research in prokaryotic nitrogen control; to
      show the ubiquity of the ntr system, at least in gram-negative organisms; and to
      identify those areas and groups of organisms about which there is much still to
      learn.

PMID- 8531891
TI  - Natural plasmids of filamentous fungi.
AB  - Among eukaryotes, plasmids have been found in fungi and plants but not in
      animals. Most plasmids are mitochondrial. In filamentous fungi, plasmids are
      commonly encountered in isolates from natural populations. Individual populations
      may show a predominance of one type, but some plasmids have a global
      distribution, often crossing species boundaries. Surveys have shown that strains
      can contain more than one type of plasmid and that different types appear to be
      distributed independently. In crosses, plasmids are generally inherited
      maternally. Horizontal transmission is by cell contact. Circular plasmids are
      common only in Neurospora spp., but linear plasmids have been found in many
      fungi. Circular plasmids have one open reading frame (ORF) coding for a DNA
      polymerase or a reverse transcriptase. Linear plasmids generally have two ORFs,
      coding for presumptive DNA and RNA polymerases with amino acid motifs showing
      homology to viral polymerases. Plasmids often attain a high copy number, in
      excess of that of mitochondrial DNA. Linear plasmids have a protein attached to
      their 5' end, and this is presumed to act as a replication primer. Most plasmids
      are neutral passengers, but several linear plasmids integrate into mitochondrial
      DNA, causing death of the host culture. Inferred amino acid sequences of linear
      plasmid ORFs have been used to plot phylogenetic trees, which show a fair
      concordance with conventional trees. The circular Neurospora plasmids have
      replication systems that seem to be evolutionary intermediates between the RNA
      and the DNA worlds.

PMID- 8531893
TI  - [Clinical aspects of immunoneuroendocrine alterations in HIV infection].
AB  - A number of studies confirm that any human tissue can be targeted by HIV, and
      also the endocrine system is involved during HIV infection. No endocrine adenus
      is saved by the assault of the opportunistic pathogens that overrun the organism
      unprotected due to the severe and progressive immune deficits induced by the HIV.
      As a consequence clinical, but often subclinical alterations can be detected that
      underline the close relationship among the systems of body adaptation to the
      environment (immune, endocrine, and nervous). Indeed these alterations can be
      viewed as an immunoneuroendocrine pathology. AIDS is a paradigmatic syndrome for
      the variety of immune dysfunctions, and also presents endocrine and neurological
      dysfunctions, which allow to better understand the connections among these
      systems, and the interactions of HIV with the immunoneuroendocrine dynamics.

PMID- 8531889
TI  - Control of rRNA transcription in Escherichia coli.
AB  - The control of rRNA synthesis in response to both extra- and intracellular
      signals has been a subject of interest to microbial physiologists for nearly four
      decades, beginning with the observations that Salmonella typhimurium cells grown
      on rich medium are larger and contain more RNA than those grown on poor medium.
      This was followed shortly by the discovery of the stringent response in
      Escherichia coli, which has continued to be the organism of choice for the study
      of rRNA synthesis. In this review, we summarize four general areas of E. coli
      rRNA transcription control: stringent control, growth rate regulation, upstream
      activation, and anti-termination. We also cite similar mechanisms in other
      bacteria and eukaryotes. The separation of growth rate-dependent control of rRNA
      synthesis from stringent control continues to be a subject of controversy. One
      model holds that the nucleotide ppGpp is the key effector for both mechanisms,
      while another school holds that it is unlikely that ppGpp or any other single
      effector is solely responsible for growth rate-dependent control. Recent studies
      on activation of rRNA synthesis by cis-acting upstream sequences has led to the
      discovery of a new class of promoters that make contact with RNA polymerase at a
      third position, called the UP element, in addition to the well-known -10 and -35
      regions. Lastly, clues as to the role of antitermination in rRNA operons have
      begun to appear. Transcription complexes modified at the antiterminator site
      appear to elongate faster and are resistant to the inhibitory effects of ppGpp
      during the stringent response.

PMID- 8531892
TI  - Chromosome-length polymorphism in fungi.
AB  - The examination of fungal chromosomes by pulsed-field gel electrophoresis has
      revealed that length polymorphism is widespread in both sexual and asexual
      species. This review summarizes characteristics of fungal chromosome-length
      polymorphism and possible mitotic and meiotic mechanisms of chromosome length
      change. Most fungal chromosome-length polymorphisms are currently uncharacterized
      with respect to content and origin. However, it is clear that long tandem
      repeats, such as tracts of rRNA genes, are frequently variable in length and that
      other chromosomal rearrangements are suppressed during normal mitotic growth.
      Dispensable chromosomes and dispensable chromosome regions, which have been well
      documented for some fungi, also contribute to the variability of the fungal
      karyotype. For sexual species, meiotic recombination increases the overall
      karyotypic variability in a population while suppressing genetic translocations.
      The range of karyotypes observed in fungi indicates that many karyotypic changes
      may be genetically neutral, at least under some conditions. In addition, new
      linkage combinations of genes may also be advantageous in allowing adaptation of
      fungi to new environments.

PMID- 8531894
TI  - [Severe diabetic retinopathy and renal function in non-insulin-dependent (type-2)
      diabetes mellitus].
AB  - The existence of a linkage between retinal and renal microvascular complications
      in type 2 diabetes has been so far little investigated. For this purpose we
      evaluated the presence and degree of renal dysfunction in the most serious
      clinical conditions of diabetic retinopathy. On the basis of the alterations
      evidenced by fluorescein angiography 73 type 2 diabetic patients were recruited
      and divided into the following groups: 19 patients were affected by "clinically
      significant" Macular Edema (ME), 25 subjects had Preproliferative Retinopathy
      (PrePR) and 29 patients showed Proliferative Retinopathy (PR). Mean values (M +/-
      SD) of glycosylated hemoglobin, plasma basal C-peptide, lipid profile, blood
      pressure, glomerular filtration rate, body mass index, age and known duration of
      diabetes were similar between the groups. Urinary albumin excretion rate (UAE)
      was determined for each patient on three consecutive overnight collections
      (pg/min). Even though the distribution of normo (UAE < 20 micrograms/min), micro
      (UAE:20-200) and macroalbuminuric (UAE > 200) patients did not significantly
      differ between the groups, mean values of UAE increased significantly in PrePR
      (371.1 +/- 532.2) and PR (300.7 +/- 717.3) with respect to ME (35.4 +/- 73.1; p <
      0.05). The evaluation of all patients recruited for the study, independently of
      the kind of retinal alteration, showed that 56.8% of them had no sign of even
      incipient renal dysfunction, in spite of the advanced retinal damage. When
      considering those patients affected by both retinal and renal complications
      (43.2%) the prevalence of renal involvement resulted different in the three
      conditions investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8531895
TI  - [Effect of GH/IGF-I deficiency on bone and collagen turnover in children and
      adults with GH deficiency].
AB  - Serum bone Gla protein (BGP), marker of osteoblastic function, carboxyterminal
      cross-linked telopeptide of type I collagen (ICTP), index of bone resorption, and
      aminoterminal propeptide of type III procollagen, marker of collagen synthesis,
      were evaluated in children with GH deficiency (GHD), in adults with childhood
      onset GHD and in adults with acquired GHD in adultlife. In children with GHD,
      serum BGP (12.7 +/- 0.5 ng/ml), ICTP (8.5 +/- 0.9 ng/ml) and PIIINP (3.4 +/- 0.4
      ng/ml) were significantly lower (p < 0.0001, p < 0.0001 and p < 0.001,
      respectively) than those observed in a sex and age matched control group
      (BGP:18.9 +/- 0.9 ng/ml, ICTP: 14.4 +/- 0.6 ng/ml, PIIINP: 6.7 +/- 0.7 ng/ml). In
      adults with childhood onsed GHD, BGP levels (3.7 +/- 0.4 ng/ml) were
      significantly lower (p < 0.0001) than those recorded in a sex and age matched
      control group (5.4 +/- 0.1 ng/ml), while ICTP (4.7 +/- 0.7 ng/ml) and PIIINP (3.7
      +/- 0.5 ng/ml) levels were similar to those found in controls (ICTP: 4.1 +/- 0.3
      ng/ml; PIIINP: 3.3 +/- 0.2 ng/ml). In adults with acquired GHD, serum BGP (5.3 +/
      0.4 ng/ml), ICTP (3.8 +/- 0.4 ng/ml) and PIIINP (3.6 +/- 0.3 ng/ml) levels were
      not significantly different from those recorded in controls (BGP: 5.4 +/- 0.1
      ng/ml, ICTP: 4.1 +/- 0.3 ng/ml, PIIINP: 3.3 +/- 0.2 ng/ml).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8531890
TI  - Production and function of cytokines in natural and acquired immunity to Candida
      albicans infection.
AB  - Host resistance against infections caused by the yeast Candida albicans is
      mediated predominantly by polymorphonuclear leukocytes and macrophages. Antigens
      of Candida stimulate lymphocyte proliferation and cytokine synthesis, and in both
      humans and mice, these cytokines enhance the candidacidal functions of the
      phagocytic cells. In systemic candidiasis in mice, cytokine production has been
      found to be a function of the CD4+ T helper (Th) cells. The Th1 subset of these
      cells, characterized by the production of gamma interferon and interleukin-2, is
      associated with macrophage activation and enhanced resistance against
      reinfection, whereas the Th2 subset, which produces interleukins-4, -6, and -10,
      is linked to the development of chronic disease. However, other models have
      generated divergent data. Mucosal infection generally elicits Th1-type cytokine
      responses and protection from systemic challenge, and identification of cytokine
      mRNA present in infected tissues of mice that develop mild or severe lesions does
      not show pure Th1- or Th2-type responses. Furthermore, antigens of C. albicans,
      mannan in particular, can induce suppressor cells that modulate both specific and
      nonspecific cellular and humoral immune responses, and there is an emerging body
      of evidence that molecular mimicry may affect the efficiency of anti-Candida
      responses within defined genetic contexts.

PMID- 8531896
TI  - Sumatriptan does not stimulate PRL and GH secretion in acromegaly.
AB  - OBJECTIVE: Serotoninergic receptors are involved in the regulation of PRL and GH
      secretion. We studied the effects of sumatriptan, a new 5-HT1D receptor agonist,
      on PRL and GH secretion in active acromegaly. EXPERIMENTAL DESIGN: After their
      informed consent, all subjects were submitted to sumatriptan or placebo
      administration in single blind and in a random order. The time interval between
      the tests was of 7 days. ENVIRONMENT: We examined all patients in the morning,
      after 12 hours of fasting. All subjects were in recumbent position during the
      tests. Pulse rate and blood pressure were monitored during the test. SUBJECTS:
      Eight acromegalics (42-65 years) and 10 age-matched (33-63 years) normal
      subjects. PROTOCOL: Blood samples were taken after needle insertion kept patent
      by slow saline solution infusion. PRL and GH secretion were evaluated after
      sumatriptan (6 mg sc) and placebo. Blood samples were taken before (45, 15 and 0
      minutes) and every 15 minutes for 2 hours after sumatriptan or placebo
      administration. RESULTS: No significant changes in PRL secretion were observed
      after sumatriptan in both groups of subjects. A significant increase in GH levels
      after sumatriptan was observed in controls but not in acromegalics. An age
      related negative trend in GH response to sumatriptan was observed in controls.
      CONCLUSIONS: Our study indicated that 5-HT1D receptors are not involved in PRL
      and GH secretion in middle-aged acromegalics.

PMID- 8531897
TI  - 131I MIBG/111In octreotide mismatch in a patient with liver metastases secondary
      to a carcinoid of unknown origin.
AB  - Carcinoids, tumors arising from enterochromaffin cells, represent the most common
      type of gastrointestinal endocrine neoplasm; they are often multiple and may
      appear anywhere in the gut. Carcinoid tumors may also occur in bronchi and
      ovaries. Classic symptomatology includes secretory diarrhea, flushing, edema,
      bronchospasm and cutaneous teleangectasias; however, over 30% of patients with
      demonstrably elevated serotonin levels may not exhibit any symptoms at all. The
      diagnosis of carcinoid tumor is typically made by measurement of 24-hour urinary
      excretion of 5-hydroxyindoloacetic acid. Commonly, tumor localisation is
      established with CT, US, NMR and arteriography. MIBG scintigraphy is also used to
      visualize tumors deriving from neuroendocrine cells as carcinoid. These tumors
      may express somatostatin receptors located on the cell surface. Therefore 111In
      Octreotide (Octreoscan), a somatostatin analogue, can be employed for tumor
      localisation. A 32-years-old man with liver metastases secondary to a carcinoid
      tumor of unknown origin is presented. Classic carcinoid symptoms were absent.
      Diagnosis was supported by elevated values of urinary 5-hydroxyindolocetic acid
      and liver fine-needle aspiration. Abdominal US and CT scan detected only liver
      masses but not the primary tumor. Arteriography was not performed. 131I MIBG and
      111I octreotide scans both failed in locating the primary cancer too; only the
      second tracer showed marked uptake in liver metastases. Beside localization,
      these two tracers give also informations about the following therapy especially
      in malignant tumors where local resection isn't an adequate treatment.

PMID- 8531898
TI  - [Tolosa Hunt syndrome and autoimmune polyglandular syndrome. A rare case report].
AB  - The authors refer to a case report in which two rare clinical syndromes, the
      Tolosa Hunt Syndrome (THS) and the polyglandular auto-immune syndrome (PGA) co
      exist in the same patient and make a detailed analysis of the literature
      regarding this kind of diseases. The THS is a rare clinical condition
      characterized by a painful ophthalmoplegia due to an involvement of the cranial
      nerves and of the sympathetic nerve-fibres going through the cavernous sinus and
      the superior orbit cavity. Nowadays the diagnosis of TSH is made by high
      resolution computerized tomography aimed at the cavernous sinus and the upper
      orbital cavity. This method allows to notice if at the basis of this syndrome
      there are vascular, neoplastic or inflammatory diseases or if, as in e case here
      presented, by exclusion, we must think of an inflammatory process with unknown
      pathogenesis. In this case report the patient under observation process to be
      affected by THS and also by auto-immune polyglandular syndrome type III, as she
      was affected by diabetes type I, Basedow disease and alopecia. The authors
      believe that an auto-immune mechanism can be at basis of the THS, and this fact
      has already been pointed out in the literature in two previous works. An
      important feature of this case report has been the definitive improvement of the
      symptoms by an antithyroid effect and, also, by an immune suppressor activity.
      The Authors hope that there will be reported a greater number of cases pointing
      to the coexistence of the THS with autoimmune diseases.

PMID- 8531899
TI  - Attitude adjustment. A complacent public tunes out the AIDS epidemic.

PMID- 8531900
TI  - HIV: an endemic health problem in Minnesota.

PMID- 8531901
TI  - Management of HIV infection. A 1995-96 overview for the clinician.
AB  - Although the challenges of HIV/AIDS care may seem overwhelming, we are better
      able than ever to positively affect the course of HIV for each individual
      patient. Treatment goals involve three areas: 1) Antiretroviral drugs aimed at
      retarding the rate of HIV replication, thus reducing the rate of damage to the
      immune system; 2) drugs used to treat or prevent opportunistic infections seen in
      the context of HIV-related immune deficiency; and 3) drugs used to treat symptoms
      or syndromes commonly seen in these patients (including dementia and wasting
      syndrome). The multitude of clinical problems seen in advanced HIV disease leads
      to significant polypharmacy and costs resulting in a very complex and confusing
      situation. I recommend that physicians with little HIV experience link up with an
      HIV specialist when caring for HIV-infected patients to optimize access to the
      best therapies or research studies currently available. With no cure in sight,
      physicians need to focus on educating the public and patients about how to avoid
      HIV infection and to identify persons who are infected to minimize spread.

PMID- 8531902
TI  - Directions in HIV/AIDS research. A Minnesota perspective.
AB  - Clinical studies involving HIV therapeutics are becoming ever more challenging
      because of the changing epidemiology of HIV infection, the rapid evolution of
      standard clinical practice, and a more difficult economic environment for
      research. Recent studies relating to HIV pathogenesis have provided novel
      insights into the interactions between HIV, the immune system, and antiretroviral
      therapies. Current dogma now suggests that the interaction of HIV and the immune
      system is an incredibly dynamic process. HIV is an intimidating pathogen capable
      of replicating quickly and mutating very rapidly in response to antiretroviral
      therapy. An important question being studied by Minnesota-based investigators is
      how well plasma analysis reflects HIV-immune system interactions in the lymphoid
      tissue where most virus and CD4+ (T-helper) cells are located. Most of the HIV
      clinical studies in Minnesota are conducted under the auspices of the AIDS
      Clinical Trials Group (ACTG) or the AIDS Research Consortium of the Twin Cities
      (ARCTiC). Much expertise is available in Minnesota addressing a wide range of
      topics, from epidemiology, to basic virology, to prevention. To optimize patient
      access to clinical studies, we recommend that physicians discuss available
      clinical studies with an HIV investigator soon after first seeing a new HIV
      infected patient.

PMID- 8531903
TI  - HIV infection in women and children.
AB  - AIDS is increasing more rapidly among women than men and has become the fourth
      leading cause of death for women between the ages of 25 and 44 years in the
      United States. This changing epidemiological trend accounts for the increase in
      pediatric cases of HIV infection. This article summarizes features on women and
      children. We review epidemiology, clinical characteristics, vertical
      transmission, treatment, and prevention opportunities.

PMID- 8531904
TI  - Needlestick/sharps injuries and HIV exposure among health care workers. National
      estimates based on a survey of U.S. hospitals.
AB  - Exposure to HIV in the workplace is a major concern for health care workers. The
      greatest risk for bloodborne pathogen transmission is associated with
      percutaneous injuries involving hollow-bore needles contaminated with patient
      blood. Limited data are available about how many sharps injuries (SIs) and
      needlesticks (NSs) occur in the United States, with estimates ranging from
      100,000 to 1 million injuries per year. We conducted a survey of 100 infection
      control practitioners located at randomly selected U.S. hospitals to assess the
      number of SIs or NSs occurring during 1990; 65 (65%) responded. The mean number
      of NS/SIs reported was 45, with a mean of 1.1 known HIV-related NS/SIs. The
      underreporting rate was estimated to be 18.5%. Assuming that the hospitals
      provided exact numbers of injuries and were representative of the approximately
      5,100 U.S. hospitals, then about 252,000 NS/SIs were reported in U.S. hospitals
      in 1990 (95% CI = 193,000-312,000). If the under-reporting rate was 33% to 66%,
      then the point estimate for the total number of NS/SIs ranges from 378,000 to
      756,000. Similar extrapolation involving the reported number of NS/SIs
      contaminated with blood from an HIV-infected patient yields an estimate of 5,610
      exposures in 1990 (95% CI = 1,300-8,300). The number of U.S. hospital workers
      sustaining NS/SIs with potential exposure to HIV appears to be considerable.
      Efforts to reduce the risk of bloodborne pathogen transmission from NS/SIs are
      warranted.

PMID- 8531905
TI  - U.S. prisoners' access to experimental HIV therapies.
AB  - PURPOSE: To examine Department of Corrections (DOC) policies prohibiting prisoner
      participation in research studies and to assess the variables associated with
      state policies and practices relating to access by inmates in U.S. prisons to HIV
      related clinical studies and experimental therapies. METHODS: A telephone survey
      conducted in 1994-95 of DOC medical directors from 32 states throughout the
      United States to obtain information about state DOC policies and practices
      relating to HIV clinical studies. RESULTS: State policies governing prisoner
      participation in clinical trials and access to new therapies vary widely. States
      with high AIDS incidence rates, a large number of AIDS-related deaths in prison,
      and high concentrations of minorities in the correctional system were more likely
      to allow prisoners to enroll in clinical studies and to receive experimental
      medications. Overall, a relatively small number of prisoners in state prisons
      have enrolled in clinical studies. Participation of a prison representative on
      the board reviewing a clinical study was identified as an important factor in
      allowing prisoner participation in studies. CONCLUSIONS: Barriers to prisoner
      participation in clinical studies are numerous but not insurmountable. Results
      from this study have led to efforts in Minnesota to revise current policy in
      order to permit prisoner participation in studies if appropriate guidelines are
      followed.

PMID- 8531906
TI  - AIDS. Public perceptions obscure medical discourse.

PMID- 8531907
TI  - Changes in medical practice raise ethical questions.

PMID- 8531908
TI  - Two for the show: EDI and electronic commerce.

PMID- 8531909
TI  - More than medicine: caring for the AIDS patient.

PMID- 8531910
TI  - Case-control study of HIV seroconversion in health-care workers after
      percutaneous exposure to HIV-infected blood--France, United Kingdom, and United
      States, January 1988-August 1994.
AB  - Health-care workers (HCWs) are potentially at risk for human immunodeficiency
      virus (HIV) infection through occupational exposures to blood. Although
      prospective studies indicate that the estimated risk for HIV infection after a
      percutaneous exposure to HIV-infected blood is approximately 0.3% (1,2), factors
      that influence this risk have not been determined. To assess potential risk
      factors, CDC, in collaboration with French and British public health authorities,
      conducted a retrospective case-control study using data reported to national
      surveillance systems in the United States, France, and the United Kingdom. This
      report describes the study and summarizes results that suggest that risk factors
      for HIV transmission include certain characteristics of the exposure and the
      source patient; in addition, postexposure use of zidovudine (ZDV) by HCWs was
      associated with a lower risk for HIV transmission.

PMID- 8531911
TI  - Hypothermia-related deaths--New Mexico, October 1993-March 1994.
AB  - Hypothermia is an unintentional lowering of the body temperature to < or = 95 F
      (< or = 35 C) (1). From 1979 through 1992, 10,550 persons in the United States
      died from hypothermia, an average of 754 deaths per year (range: 557-1021). Most
      of these deaths occurred during winter months in three distinct climatic areas:
      northern states characterized by moderate to severe cold temperatures during
      winter (e.g., Illinois and New York); southern states where rapid changes in
      temperature occur because of the effects of weather systems (e.g., North
      Carolina, South Carolina, and Virginia); and western states in areas of high
      elevations and profound declines in temperatures at night (e.g., New Mexico and
      Arizona). From October 1993 through March 1994, a total of 23 deaths attributed
      to hypothermia were reported to the New Mexico Office of the Medical
      Investigator. This report summarizes the investigations of four of these deaths
      and the epidemiology for all 23 cases.

PMID- 8531912
TI  - Update: influenza activity--United States, 1995-96 season.
AB  - Influenza activity in the United States increased steadily from late October
      through mid-December 1995. This report summarizes influenza surveillance data
      from October 1 through December 16, 1995.

PMID- 8531913
TI  - Recommended childhood immunization schedule--United States, January-June 1996.
AB  - In January 1995, the recommended childhood immunization schedule was published in
      MMWR following issuance by the Advisory Committee on Immunization Practices
      (ACIP), the American Academy of Pediatrics, and the American Academy of Family
      Physicians (1). This schedule was the first unified schedule developed through a
      collaborative process among the recommending groups, the pharmaceutical
      manufacturing industry, and the Food and Drug Administration. This collaborative
      process should assist in maintaining a common childhood vaccination schedule and
      enabling further simplification of the schedule. This notice presents the
      recommended childhood immunization schedule for January-June 1996 (Figure 1) to
      incorporate licensure of varicella zoster virus vaccine (Var) and recommendations
      for adolescent hepatitis B vaccination.

PMID- 8531914
TI  - Carbon monoxide poisonings associated with snow-obstructed vehicle exhaust
      systems--Philadelphia and New York City, January 1996.
AB  - On January 9, 1996, CDC was notified about carbon monoxide (CO)-related morbidity
      and mortality associated with the blizzard in the northeastern United States.
      Most of these poisonings occurred among children and elderly persons and resulted
      from exposures in idling automobiles with exhaust pipes blocked by snow. This
      report summarizes three cases of CO poisoning reported to Philadelphia's Poison
      Control Center on January 8-9, and 22 cases reported in New York City on January
      8-9.

PMID- 8531915
TI  - Suicide among older persons--United States, 1980-1992.

PMID- 8531916
TI  - Outbreak of unexplained illness in a middle school--Washington, April 1994.
AB  - Mass sociogenic illness (MSI) is the occurrence of a group of nonspecific
      physical symptoms for which no organic cause can be determined and that is
      transmitted among members of a group by "line of sight." On April 22, 1994, the
      Snohomish (Washington) Health District (SHD) was notified of an outbreak of
      unexplained illness characterized by abrupt onset of nausea and headache among
      students at a middle school. This report summarizes the investigation of this
      outbreak by SHD, which determined that MSI was the most likely cause of the
      outbreak.

PMID- 8531918
TI  - Deaths associated with Hurricanes Marilyn and Opal--United States, September
      October 1995.
AB  - The 1995 hurricane season was one of the most severe in U.S. history and included
      11 hurricanes. During a 2-week period, the two most damaging storms--hurricanes
      Marilyn and Opal--made landfall in the United States. To characterize the deaths
      attributed to these storms, CDC contacted medical examiners/coroners (ME/Cs) in
      the affected areas. This report summarizes the findings of these investigations.

PMID- 8531917
TI  - Hepatitis A among persons with hemophilia who received clotting factor
      concentrate--United States, September-December 1995.
AB  - Hepatitis A outbreaks associated with receipt of clotting factor concentrate
      previously have been recognized in Europe but not in the United States (1-5).
      During September-November 1995, three cases of hepatitis A in recipients of
      Alphanate factor VIII concentrate (Alpha Therapeutic Corporation, Los Angeles,
      California) from lot number AP5014A were reported to CDC. On December 8, the
      manufacturer voluntarily withdrew Alphanate lot number AP5014A from the market.
      In addition, one case of hepatitis A in a recipient of AlphaNine S-D factor IX
      concentrate (Alpha Therapeutic Corporation) has been reported and is under
      investigation. On January 11, 1996, the manufacturer voluntarily withheld four
      lots of AlphaNine S-D from further distribution as a precautionary measure. This
      report describes these four cases, summarizes the status of the investigation of
      the cases, and provides guidelines for testing and reporting of patients who
      received these products.

PMID- 8531919
TI  - Surveillance of tuberculosis and AIDS co-morbidity--Florida, 1981-1993.
AB  - Because immunosuppression induced by human immunodeficiency virus (HIV) infection
      increases the likelihood that latent tuberculosis (TB) infection will become
      active in HIV-infected persons (1,2), in 1987, extrapulmonary or disseminated TB
      was added to the acquired immunodeficiency syndrome (AIDS) surveillance case
      definition (3), and in 1993, pulmonary TB in HIV-infected persons was added to
      the case definition (4). In Florida and other areas (5), AIDS surveillance
      activities include assessment of the completeness and validity of reported cases
      based on confidential record linkages with the TB registry and other disease
      registries. In December 1993, the Florida Department of Health and Rehabilitative
      Services (HRS) matched cases from the AIDS and TB registries to verify documented
      TB data, include more complete TB data on the AIDS registry, and identify cases
      from the AIDS registry with unreported TB. This report summarizes an analysis of
      this match, which underscored the need for collaboration and crosstraining of
      surveillance staff in AIDS and TB reporting.

PMID- 8531920
TI  - Expression of cDNA fragment encoding sperm membrane peptide in E. coli.
AB  - A secretory high-level expression cloning vector designated as pSBC-20 was
      constructed by inserting a DNA fragment encoding the signal peptide of ompA
      protein into pBV 220 vector. Any foreign DNA fragment can be inserted into the
      polylinker cloning sites located after the secretion signal sequence. The cloned
      foreign gene is under the control of the PR-PL promoter while the expression of
      the gene is regulated by the cI-gene product. The products are secreted into the
      periplasmic space of bacteria or into the medium. A recombinant plasmid (pRSD
      220) was constructed by inserting the 210 bp from RSD-2, a cDNA encoding a
      peptide fragment of human sperm protein, into the EcoRI site of pSBC-20. The E.
      coli cells transformed with pRSD-220 were propagated at 30 degrees C, then
      incubated at 42 degrees C for several hrs. The cloned gene product was secreted
      into the culture medium at a high rate. The yield was about 60 mg of gene product
      per liter of cultured medium.

PMID- 8531921
TI  - Analysis of transfer RNA during the early embryogenesis of the freshwater
      teleost, Heteropneustes fossilis.
AB  - Total RNA as well as transfer RNA were quantified from mature ova apart from four
      different embryonic stages namely mid-cleavage, early gastrula, mid-gastrula and
      organogenesis of the freshwater teleost Heteropneustes fossilis. Total RNA as
      well as transfer RNA quantity follow a similar variation pattern, being maximum
      during mid-gastrulation. When analysed by total amino acid acceptance capacity,
      transfer RNA shows its maximum activity during mid-gastrulation. This coincides
      with the higher ratio of tRNA to total RNA at this stage. The relative
      aminoacylation capacity for Ser, Gly, Asn and Thr are found to be higher (9-34%)
      compared to that for other amino acids. Total tRNA, resolved into three peaks
      upon HPLC fractionation, shows a high cumulative peak area during mid
      gastrulation and organogenesis. These results indicate a switch over of maternal
      to embryonic translation machinery during gastrulation.

PMID- 8531922
TI  - The two-hybrid: an in vivo protein-protein interaction assay.

PMID- 8531923
TI  - alpha-Crystallins, versatile stress-proteins.

PMID- 8531924
TI  - Assignment of Alu-repetitive sequences to large restriction fragments from human
      chromosomes 6 and 22.
AB  - We have employed a pulsed field gel electrophoresis and Alu hybridization
      approach for identification of large restriction fragments on chromosome 6 and
      22. This technique allows large portions of selected human chromosomes to be
      visualized as discrete hybridization signals. Somatic cell hybrid DNA which
      contains chromosome 6 or chromosome 22 was restricted with either Notl or Mlul.
      The restriction fragments were separated by pulsed field gel electrophoresis
      (PFGE) and hybridized against an Alu repetitive sequence (Blur 8). The
      hybridization signals result in a fingerprint-like pattern which is unique for
      each chromosome and each restriction enzyme. In addition, a continuous pattern of
      restriction fragments was demonstrated by gradually increasing puls times. This
      approach will also be suitable to analyze aberrant human chromosomes retained in
      somatic cell hybrids and can be used to analyze flow sorted human chromosomes. To
      this end, our method provides a valuable alternative to standard cytogenetic
      analysis.

PMID- 8531925
TI  - Nucleotide sequence of a highly repetitive element isolated from Opsariichthys
      uncirostris (Osteichthyes). O. uncirostris repetitive sequence.
AB  - A highly repetitive DNA element has been isolated from Opsariichthys uncirostris.
      It contains several oligo-dA tracts and potential regions for the secondary
      structures.

PMID- 8531926
TI  - The inhibitory domain in the Oct-2 transcription factor represses gene activity
      in a cell type-specific and promoter-independent manner.
AB  - The Oct-2 transcription factor contains an N-terminal inhibitory domain which can
      act to inhibit promoter activity when linked to either its corresponding DNA
      binding POU domain or the heterologous DNA binding domain of the yeast
      transcription factor GAL4. This inhibitory effect is independent of the number of
      DNA binding sites or their context in the target promoter. In contrast the effect
      is cell type-specific and can be relieved by over-expression of the isolated
      inhibitory domain in the absence of a DNA binding domain. These results suggest
      that the inhibitory domain acts by decreasing the activity of the basal
      transcriptional complex but that it operates indirectly by recruiting a second
      cell type-specific factor to the promoter which then interacts with the basal
      complex decreasing its activity.

PMID- 8531927
TI  - The size heterogeneity of human lysyl oxidase mRNA is due to alternate
      polyadenylation site and not alternate exon usage.
AB  - We have isolated the entire gene coding for human lysyl oxidase. Coding and
      untranslated domains of human lysyl oxidase mRNA were found in 7 exons,
      distributed throughout approximately 14 kb of human genomic DNA. The appearance
      of exon sequences in lysyl oxidase mRNA in several human tissues was determined
      using a reverse transcriptase - PCR assay. In contrast to a previous report, this
      analysis has unambiguously shown that the size heterogeneity of lysyl oxidase
      mRNA was not due to alternate usage of any of the exons of the lysyl oxidase
      gene. Moreover, DNA sequence analysis of the entire 3.8 kb 3'-untranslated region
      (UTR) within exon 7 revealed multiple poly-adenylation sites which were shown to
      be differentially expressed in human skin fibroblasts. This differential usage of
      polyadenylation sites within the 3'-UTR explains the appearance of multiple lysyl
      oxidase mRNAs of different sizes.

PMID- 8531928
TI  - Sensitivity and specificity of an isoelectric focusing fraction of Blastomyces
      dermatitidis yeast lysate antigen for the detection of canine blastomycosis.
AB  - Blastomyces dermatitidis yeast lysate antigen (T-58, dog isolate) fractions
      prepared using the Rotofor preparative isoelectric focusing (IEF) cell (Bio-Rad)
      were compared with B. dermatitidis yeast lysate and filtrate reagents with
      respect to the detection of antibodies in sera from dogs with blastomycosis,
      histoplasmosis, coccidioidomycosis, cryptococcosis and aspergillosis. A
      horseradish peroxidase enzyme immunoassay with Turbo TMB substrate was used in
      the study. One particular IEF fraction (pH 4.3) was optimal in the assay, and it
      exhibited greater sensitivity (100%) and specificity (93%) than the lysate or
      filtrate preparations. The highest degree of cross-reactivity was encountered
      with the histoplasmosis and coccidioidomycosis specimens and considerably less
      with the cryptococcosis and aspergillosis sera. Studies are in progress to purify
      further the optimal IEF fraction.

PMID- 8531929
TI  - Effects of three azole derivatives on the lipids of different strains of
      Cryptococcus neoformans.
AB  - The comparative effects of ketoconazole, itraconazole and fluconazole on the
      lipids of four Cryptococcus neoformans strains were investigated. Quantitative
      analysis of lipids and sterols was completed, as well as qualitative analysis of
      sterols by thin-layer chromatography and by the ultraviolet spectrum. Growth of
      the cryptococcal isolates in the presence of the azoles derivatives
      concentrations below the minimum inhibitory concentration resulted in significant
      alterations in the lipid and sterol contents as compared with the control values.
      Furthermore, lanosterol was detected in these azole-treated cells. These results
      were in complete agreement with the proposed mechanism of action of azoles, which
      act through the inhibition of ergosterol biosynthesis, with resultant
      accumulation of lanosterol. Ketoconazole was found to be the least effective
      drug, as determined from a comparison of the effect of the three azoles on the
      sterol content of the four strains. Itraconazole showed to be the most effective
      drug, probably because of its high lipophilicity, which allows the drug to
      penetrate into fungi cells more efficiently.

PMID- 8531930
TI  - Preliminary studies of the antifungal activities of some medicinal plants against
      Basidiobolus and some other pathogenic fungi.
AB  - The antifungal activities of extracts of 10 medicinal plants collected from south
      eastern parts of Nigeria were tested against seven pathogenic fungi using the
      broth dilution and agar plate methods. All the extracts at 1:10 dilution
      inhibited the growth of Basidiobolus haptosporus and B. ranarum but did not
      inhibit that of Aspergillus fumigatus, Geotrichum candidum and Candida albicans.
      While extracts from Piper guineense, Ocimum gratissimum, Moringa oleifera and
      Erythrophleum suaveolens inhibited the growth of Trichophyton rubrum and T.
      mentagrophytes, those from Fatropha curcas, Mitracarpus villosus, Azadirachta
      indica and Gongronema latifolium failed to do so at 1:10 dilution. Extract from
      Piper sp. was also able to inhibit the growth of B. haptosporus at a
      concentration as low as 1:80 dilution followed by those of Ocimum and Rauvolfia
      spp. at 1:40 dilution. These results indicate possible use of certain plant
      extracts in the treatment of subcutaneous phycomycosis in humans and animals.

PMID- 8531931
TI  - UV susceptibility and negative phototropism of dermatophytes.
AB  - High doses of ultraviolet radiation (UVR) have well-known inhibitory effects upon
      dermatophytes. In the present study, the effect of repetitive low doses of UVR on
      mycelial growth of dermatophytes was tested. Pellets of Trichophyton rubrum, T.
      mentagrophytes and Microsporum canis were placed between two thin layers of
      Sabouraud glucose agar. Obverse, reverse or both sides of these 'sandwich' agars
      were irradiated for 10 days twice daily with 0.13 or 0.17 J cm-2 UVB. To simulate
      microaerophilic conditions, one or both agar sides were covered by transparent
      airtight plastic lids. In addition, T. rubrum was also grown as usual on plates
      of Sabouraud glucose agar without any covering, and irradiated on its obverse
      side twice daily with UVA (13.5 J cm-2), UVB (0.17, 0.34 or 0.69 J cm-2) or
      infrared light, or once only with 3.8-15.1 J cm-2 UVB. As a result, thallus
      diameters of all strains were found to be reduced by repetitive UVB irradiation
      under both aerobic and microaerophilic growth conditions. T. rubrum was
      unaffected by infrared irradiation, responded with an increased pigmentation to
      UVA (13.5 J cm-2 twice daily) and was inhibited by a single dose of 15.1 J cm-2
      UVB. Negative phototropism of dermatophytes is a new observation. It may be
      biologically relevant as a mechanism to evade harmful doses of UVR.

PMID- 8531932
TI  - Comparative studies on keratinase production of Trichophyton mentagrophytes
      strains of animal origin.
AB  - Over a period of 28 days, 10 Trichophyton mentagrophytes strains were examined
      for their ability to secrete keratinolytic enzymes. Production of enzymes was
      stimulated by various keratins used as substrates. Duration and intensity of
      keratinase secretion were strongly influenced by the keratinous substrate.
      Duration and intensity of the enzyme production also differed among the 10
      dermatophyte strains. Five different enzymes were isolated with molecular weights
      ranging from 28 kDa to 65 kDa. The different enzymes might be produced by
      different varieties of the species Trichophyton mentagrophytes.

PMID- 8531933
TI  - Short therapy for tinea unguium with terbinafine: four different courses of
      treatment.
AB  - Terbinafine has partly solved the well-known problems in the treatment of
      dermatophyte nail infections. The aim of our study was to assess the
      effectiveness of very short treatment of dermatophyte nail infections with four
      different courses of terbinafine with or without chemical onycholysis. For this
      purpose, 60 patients, divided into four groups, were given different courses of
      treatment with oral terbinafine. Clinical, mycological and tolerability tests
      were performed before, during and after treatment. Clear microscopy and culture
      findings confirmed cure rates in the four groups of 95%, 95%, 70% and 100%
      without any side-effects. In conclusion, terbinafine has proved to be effective
      and well tolerated in the very short-term treatment of dermatophyte nail
      infections.

PMID- 8531934
TI  - Phialophora verrucosa infection in an AIDS patient.
AB  - Phialophora verrucosa is one of several pathogenic dematiaceous fungi associated
      with chromomycosis and occasionally phaeohyphomycosis. Infection appears to be
      increasing in frequency in both immunocompromised and presumably healthy
      patients. Medical therapy is often difficult, and a wide variety of antifungal
      agents have been tried with varying degrees of success. We report a patient with
      acquired immunodeficiency syndrome (AIDS) and extensive cutaneous fungal
      infection due to Phialophora verrucosa. The disease failed to respond to
      ketoconazole, but regression of the lesions was obtained with itraconazole.

PMID- 8531935
TI  - Rhinosporidiosis in Saudi Arabia: report of four cases.
AB  - Four cases of rhinosporidiosis occurring in Indian expatriate workers in Saudi
      Arabia are described. The prevalence of such cases in other countries of the
      Arabian Gulf is reviewed.

PMID- 8531936
TI  - Rhinosporidiosis in India: a case report and review of literature.
AB  - A 21-year-old male from Kerala, south India, who had been living in Chandigarh
      for the last 4 years presented with a nasal polyp in the left nasal cavity. On
      histopathological examination, it was found to be due to rhinosporidiosis. This
      disease is not uncommon in south India, but few case reports have been documented
      from north India. This paper presents a case report of rhinosporidiosis from the
      Government Medical College and Hospital, Chandigarh, and a review of literature
      of the disease.

PMID- 8531937
TI  - Pityriasis versicolor in a newborn.
AB  - Pityriasis versicolor is a superficial mycosis that rarely afflicts children. We
      present a case in a 2-month-old male baby in good health, with hyper- and
      hypopigmented macules located in the cervical region and on the scalp, face and
      chest. Moreover, we report our record of cases in infancy and the predisposing
      factors.

PMID- 8531938
TI  - Trichophyton soudanense in Italy.
AB  - Trichophyton soudanense is an anthropophilic dermatophyte originating in Africa.
      Over the last 30 years sporadic cases have been reported in countries that had
      colonial relations with the endemic areas. In recent times, as a result of
      growing racial mixing linked to migratory movements, this strain has become
      increasingly integrated with the species most commonly responsible for
      dermatophytoses. This phenomenon has occurred, although only recently, in Italy
      too, where there has been a heavy influx of foreign immigrants over the last few
      years.

PMID- 8531940
TI  - The aetiological agents of superficial cutaneous mycoses in Jos, Plateau State of
      Nigeria.
AB  - A survey of superficial skin mycoses was carried out among miners and office
      workers employed in different establishments in Jos, Nigeria. Mycotic infection
      was demonstrable by microscopy and culture in 45 (10.4%) subjects: 20 males and
      25 females. Malassezia furfur was the predominant aetiological agent, followed by
      Candida albicans and Trichophyton soudanense. Other aetiological agents
      frequently recovered were T. rubrum., T. mentagrophytes., Microsporum audouinii
      and Trichosporon beigelii.

PMID- 8531939
TI  - Tinea capitis due to Trichophyton rubrum in adult women.

PMID- 8531941
TI  - Dermatophytes from cases of skin disease in cats and dogs in Turin, Italy.
AB  - In urban environments, pet animals such as dogs and cats may be largely
      responsible for the progressive increase of zoophilic over anthropophilic
      dermatophytes in the aetiology of human dermatophytoses. Mapping, in each city,
      of the natural foci of zoophilic dermatophytes may thus be important for
      understanding the epidemiology of human dermatophytoses, and for planning
      preventive measures. We have surveyed dogs and cats suspected of carrying
      dermatophytic lesions in the Turin area. Hairs, skin scrapings and the contents
      of pustules or vesicles were inoculated on Dermasel agar supplemented with
      choramphenicol and cycloheximide. The mating type of the isolates was checked,
      testing their compatibility with the two mating types of Arthroderma simii
      Stockdale, Mackenzie and Austwick. We isolated dermatophytes from about 40% of
      the cases examined. Microsporum canis Bodin was the only dermatophyte found in
      the lesions. In the cats the lesions were more frequent, in the dogs more severe.
      Animals less than a year old and male dogs were most often affected. Some cases
      of transmission of the infection between animals and from animals to man are
      described. All the isolates of M. canis, tested for mating behaviour, were non
      reactive.

PMID- 8531942
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-1996. A 69-year-old woman with severe, persistent congestive
      heart failure after treatment for bacteremia.

PMID- 8531943
TI  - Prognostic implications of silent myocardial ischemia.

PMID- 8531944
TI  - Living with Parkinson's disease.

PMID- 8531945
TI  - The challenges posed by managed behavioral health care.

PMID- 8531946
TI  - Aspirin and the risk of colorectal cancer in women.

PMID- 8531947
TI  - Aspirin and the risk of colorectal cancer in women.

PMID- 8531948
TI  - Aspirin and the risk of colorectal cancer in women.

PMID- 8531949
TI  - Aspirin and the risk of colorectal cancer in women.

PMID- 8531950
TI  - Aspirin and the risk of colorectal cancer in women.

PMID- 8531951
TI  - Aspirin and the risk of colorectal cancer in women.

PMID- 8531952
TI  - Epstein-Barr virus and nasopharyngeal cancer.

PMID- 8531953
TI  - Epstein-Barr virus and nasopharyngeal cancer.

PMID- 8531954
TI  - Race, sex, drug use, and human immunodeficiency virus disease.

PMID- 8531955
TI  - Race, sex, drug use, and human immunodeficiency virus disease.

PMID- 8531956
TI  - Incentive spirometry in sickle cell crisis.

PMID- 8531957
TI  - Paddler's palsy.

PMID- 8531958
TI  - Single-day praziquantel therapy for neurocysticercosis.

PMID- 8531959
TI  - Managed care and mental health.

PMID- 8531960
TI  - Prognostic importance of myocardial ischemia detected by ambulatory monitoring
      early after acute myocardial infarction.
AB  - BACKGROUND: After an acute myocardial infarction, it is important to determine
      the risk of a subsequent coronary event. We studied the prognostic value of
      myocardial ischemia detected by ambulatory electrocardiographic (ECG) monitoring
      in patients who had recently had an acute myocardial infarction. METHODS: Five to
      seven days after acute myocardial infarction, 406 patients underwent 48-hour
      ambulatory ECG monitoring, with submaximal exercise testing before discharge and
      measurement of the left ventricular ejection fraction within 28 days after
      infarction. Death, nonfatal myocardial infarction, and admission to the hospital
      because of unstable angina were the principal end points recorded during the one
      year follow-up period. RESULTS: The overall incidence of myocardial ischemia
      detected by ambulatory ECG monitoring was 23.4 percent. The mortality rates at
      one year were 11.6 percent among the patients with ischemia and 3.9 percent among
      those without ischemia (P = 0.009); 3.9 percent among the patients with a
      positive exercise test, 3.0 percent among those with a negative exercise test,
      and 16.4 percent among those in whom an exercise test was not performed (P <
      0.001); and 3.6 percent among the patients with an ejection fraction greater than
      50 percent, 3.5 percent among those with an ejection fraction between 35 and 50
      percent, and 18.2 percent among those with an ejection fraction below 35 percent
      (P = 0.001). Using multiple logistic regression, we found that no diagnostic test
      performed after myocardial infarction provided additional prognostic information
      beyond that provided by the standard clinical variables used to predict the risk
      of death. When nonfatal myocardial infarction and admission to the hospital
      because of unstable angina were also included as outcome variables, ambulatory
      monitoring for ischemia was the only test that contributed significantly to the
      model. For the patients with ischemia detected by ambulatory monitoring, as
      compared with those who did not have evidence of ischemia, the odds ratio was 2.3
      (95 percent confidence interval, 1.2 to 4.5) for death or nonfatal myocardial
      infarction (P = 0.009) and 2.8 (95 percent confidence interval, 1.6 to 4.8) for
      death, nonfatal myocardial infarction, or admission to the hospital because of
      unstable angina (P < 0.001). CONCLUSIONS: Myocardial ischemia detected by
      ambulatory ECG monitoring is common early after acute myocardial infarction and
      provides prognostic information beyond that available from standard clinical
      information.

PMID- 8531961
TI  - Prevalence of parkinsonian signs and associated mortality in a community
      population of older people.
AB  - BACKGROUND: Older people frequently have signs of parkinsonism, but information
      about the prevalence of parkinsonism and mortality among those with the condition
      in the community is limited. METHODS: A stratified random sample of 467 residents
      of East Boston, Massachusetts, 65 years of age or older, were given structured
      neurologic examinations. Using uniform, specified combinations of parkinsonian
      signs, we estimated the prevalence of four categories of signs--bradykinesia,
      gait disturbance, rigidity, and tremor--and of parkinsonism, defined as the
      presence of two or more categories. We did not study Parkinson's disease because
      it could not be distinguished from other conditions that can cause parkinsonism.
      Proportional-hazards models were used to compare the risk of death among people
      with and those without parkinsonism. RESULTS: One hundred fifty-nine persons had
      parkinsonism, 301 did not, and 7 could not be classified. The overall prevalence
      estimates were 14.9 percent for people 65 to 74 years of age, 29.5 percent for
      those 75 to 84, and 52.4 percent for those 85 and older. With a mean follow-up
      period of 9.2 years, 124 persons with parkinsonism (78 percent) and 146 persons
      without (49 percent) died. Adjusted for age and sex, the overall risk of death
      among people with parkinsonism was 2.0 (95 percent confidence interval, 1.6 to
      2.6) times that among people without. Among people with parkinsonism, the
      presence of gait disturbance was associated with an increased risk of death.
      CONCLUSIONS: Parkinsonism is very common among people over the age of 65, and its
      prevalence increases markedly with age. Parkinsonism is associated with a twofold
      increase in the risk of death, which is strongly related to the presence of a
      gait disturbance.

PMID- 8531962
TI  - Mutations in the nonstructural protein 5A gene and response to interferon in
      patients with chronic hepatitis C virus 1b infection.
AB  - BACKGROUND: A region associated with sensitivity to interferon has been
      identified in the nonstructural protein 5A (NS5A) of hepatitis C virus (HCV)
      genotype 1b. The region spans amino acid residues 2209 to 2248 (NS5A2209-2248) of
      HCV-J, a strain of HCV-1b whose complete genomic sequence has been identified. We
      examined whether the NS5A2209-2248 sequence present before therapy could be used
      as a predictor of the response to interferon therapy in patients with chronic HCV
      1b infection. METHODS: We retrospectively analyzed 84 patients with chronic HCV
      1b infection who had received interferon alfa (total dose, 516 million to 880
      million units) for six months. Pretreatment serum samples were analyzed. The
      amino acid sequence of NS5A2209-2248 was determined by direct sequencing of the
      HCV genome amplified by the polymerase chain reaction (PCR) and was compared with
      the established sequence for HCV-J. RESULTS: A complete response, as evidenced by
      the absence of HCV RNA in serum on nested reverse-transcription PCR for six
      months after therapy, did not occur in any of the 30 patients whose NS5A2209-2248
      sequences were identical to that of HCV-J (wild type). Five of 38 patients (13
      percent) with 1 to 3 changes in NS5A2209-2248 (intermediate type) had complete
      responses, as did all 16 patients with 4 to 11 amino acid substitutions (mutant
      type), indicating that the mutant type was significantly associated with a
      complete response (P < 0.001). Although baseline serum HCV RNA levels, as
      measured by a branched-chain DNA assay, were lower in patients with the mutant
      type of NS5A2209-2248 than in those with the other types (P < 0.001),
      multivariate analyses revealed that the number of amino acid substitutions in
      NS5A2209-2248 was the only variable associated with an independent effect on the
      outcome of interferon therapy (odds ratio, 5.3; 95 percent confidence interval,
      1.6 to 18; P = 0.007). CONCLUSIONS: In patients with chronic HCV-1b infection,
      there is a substantial correlation between responses to interferon and mutations
      in the NS5A gene.

PMID- 8531963
TI  - Risk of colorectal cancer in the families of patients with adenomatous polyps.
      National Polyp Study Workgroup.
AB  - BACKGROUND: The adenoma-adenocarcinoma sequence in colorectal cancer suggests an
      increased risk of colorectal cancer in the families of patients with adenomatous
      polyps. METHODS: A random sample of participants in the National Polyp Study who
      had newly diagnosed adenomatous polyps were interviewed for information on the
      history of colorectal cancer in their parents and siblings. The risk of
      colorectal cancer in family members was analyzed according to the characteristics
      of the patients with adenomas and in comparison with a sample of patients'
      spouses, who served as controls. RESULTS: Among the patients with adenomas, 1199
      provided information on whether they had a family history of colorectal cancer.
      After the exclusion of families for which information was incomplete and of 48
      patients who had been referred for colonoscopy solely because they had a family
      history of colorectal cancer, there were 1031 patients with adenomas, 1865
      parents, 2381 siblings, and 1411 spouse controls. The relative risk of colorectal
      cancer, adjusted for the year of birth and sex, was 1.78 for the parents and
      siblings of the patients with adenomas as compared with the spouse controls (95
      percent confidence interval, 1.18 to 2.67). The relative risk for siblings of
      patients in whom adenomas were diagnosed before 60 years of age was 2.59 (95
      percent confidence interval, 1.46 to 4.58) as compared with the siblings of
      patients who were 60 or older at the time of diagnosis and after adjustment for
      the sibling's year of birth and sex and a parental history of colorectal cancer.
      The risk increased with decreasing age at the time of the diagnosis of adenoma (P
      for trend < 0.001). The relative risk for the siblings of patients who had a
      parent with colorectal cancer, as compared with those who had no parent with
      cancer, was 3.25 (95 percent confidence interval, 1.92 to 5.52), after adjustment
      for the sibling's year of birth and sex and the patient's age at diagnosis.
      CONCLUSIONS: Siblings and parents of patients with adenomatous polyps are at
      increased risk for colorectal cancer, particularly when the adenoma is diagnosed
      before the age of 60 or--in the case of siblings--when a parent has had
      colorectal cancer.

PMID- 8531964
TI  - Images in clinical medicine. Fracture of a retention wire in an atrial J
      pacemaker lead.

PMID- 8531965
TI  - Cardiac pacing.

PMID- 8531966
TI  - Obstructive sleep apnea.

PMID- 8531967
TI  - BRCA1 mutations in a population-based sample of young women with breast cancer.
AB  - BACKGROUND: Inherited mutations in the BRCA1 gene are associated with a high risk
      of breast and ovarian cancer in some families. However, little is known about the
      contribution of BRCA1 mutations to breast cancer in the general population. We
      analyzed DNA samples from women enrolled in a population-based study of early
      onset breast cancer to assess the spectrum and frequency of germ-line BRCA1
      mutations in young women with breast cancer. METHODS: We studied 80 women in whom
      breast cancer was diagnosed before the age of 35, and who were not selected on
      the basis of family history. Genomic DNA was studied for BRCA1 mutations by
      analysis involving single-strand conformation polymorphisms and with allele
      specific assays. Alterations were defined by DNA sequencing. RESULTS: Germ-line
      BRCA1 mutations were identified in 6 of the 80 women. Four additional rare
      sequence variants of unknown functional importance were also identified. Two of
      the mutations and three of the rare sequence variants were found among the 39
      women who reported no family history of breast or ovarian cancer. None of the
      mutations and only one of the rare variants was identified in a reference
      population of 73 unrelated subjects. CONCLUSIONS: Alterations in BRCA1 were
      identified in approximately 10 percent of this cohort of young women with breast
      cancer. The risk of harboring a mutation was not limited to women with family
      histories of breast or ovarian cancer. These results represent a minimal estimate
      of the frequency of BRCA1 mutations in this population. Comprehensive methods of
      identifying BRCA1 mutations and understanding their importance will be needed
      before testing of women in the general population can be undertaken.

PMID- 8531968
TI  - Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast
      cancer.
AB  - BACKGROUND: Mutations in a germ-line allele of the BRCA1 gene contribute to the
      familial breast cancer syndrome. However, the prevalence of these mutations is
      unknown in women with breast cancer who do not have the features of this familial
      syndrome. We sought BRCA1 mutations in women who were given a diagnosis of breast
      cancer at an early age, because early onset is characteristic of a genetic
      predisposition to cancer. METHODS: Clinical information and peripheral-blood
      mononuclear cells were obtained from 418 women from the Boston metropolitan area
      in whom breast cancer was diagnosed at or before the age of 40. A comprehensive
      BRCA1 mutational analysis, involving automated nucleotide sequencing and a
      protein-truncation assay, was undertaken in 30 of these women, who had breast
      cancer before the age of 30. In addition, the BRCA1 mutation 185delAG, which is
      prevalent in the Ashkenazi Jewish population, was sought with an allele-specific
      polymerase-chain-reaction assay in 39 Jewish women among the 418 women who had
      breast cancer at or before the age of 40. RESULTS: Among 30 women with breast
      cancer before the age of 30, 4 (13 percent) had definite, chain-terminating
      mutations and 1 had a missense mutation. Two of the four Jewish women in this
      cohort had the 185delAG mutation. Among the 39 Jewish women with breast cancer at
      or before the age of 40, 8 (21 percent) carried the 185delAG mutation (95 percent
      confidence interval, 9 to 36 percent). CONCLUSIONS: Germ-line BRCA1 mutations can
      be present in young women with breast cancer who do not belong to families with
      multiple affected members. The specific BRCA1 mutation known as 185delAG is
      strongly associated with the onset of breast cancer in Jewish women before the
      age of 40.

PMID- 8531969
TI  - Passive smoking and impaired endothelium-dependent arterial dilatation in healthy
      young adults.
AB  - BACKGROUND: Passive smoking has been linked to an increased risk of dying from
      atherosclerotic heart disease. Since endothelial dysfunction is an early feature
      of atherogenesis and occurs in young adults who actively smoke cigarettes, we
      hypothesized that passive smoking might also be associated with endothelial
      damage in healthy young-adult nonsmokers. METHODS: We studied 78 healthy subjects
      (39 men and 39 women) 15 to 30 years of age (mean +/- SD, 22 +/- 4): 26 control
      subjects who had never smoked or had regular exposure to environmental tobacco
      smoke, 26 who had never smoked but had been exposed to environmental tobacco
      smoke for at least one hour daily for three or more years, and 26 active smokers.
      Using ultrasonography, we measured the brachial-artery diameter under base-line
      conditions, during reactive hyperemia (with flow increase causing endothelium
      dependent dilatation), and after sublingual administration of nitroglycerin (an
      endothelium-independent dilator). RESULTS: Flow-mediated dilatation was observed
      in all control subjects (8.2 +/- 3.1 percent; range, 2.1 to 16.7) but was
      significantly impaired in the passive smokers (3.1 +/- 2.7 percent; range, 0 to
      9; P < 0.001 for the comparison with the controls) and in the active smokers (4.4
      +/- 3.1 percent; range, 0 to 10; P < 0.001 for the comparison with the controls;
      P = 0.48 for the comparison with the passive smokers). In the passive smokers,
      there was an inverse relation between the intensity of exposure to tobacco smoke
      and flow-mediated dilatation (r = -0.67, P < 0.001). In contrast, dilatation
      induced by nitroglycerin was similar in all groups. CONCLUSIONS: Passive smoking
      is associated with dose-related impairment of endothelium-dependent dilatation in
      healthy young adults, suggesting early arterial damage.

PMID- 8531971
TI  - Images in clinical medicine. Paget's disease of bone.

PMID- 8531970
TI  - A comparison of fecal occult-blood tests for colorectal-cancer screening.
AB  - BACKGROUND: Hemoccult II, a widely used guaiac test for fecal occult blood, has a
      low sensitivity for detecting colorectal neoplasms in asymptomatic patients at
      average risk. In such patients, the performance characteristics of screening
      tests developed to improve on Hemoccult II are not known. METHODS: A set of three
      fecal occult-blood tests--Hemoccult II; Hemoccult II Sensa, a more sensitive
      guaiac test; and HemeSelect, an immunochemical test for human hemoglobin--was
      mailed to all patients 50 years of age or older who were scheduled for personal
      health appraisals at the Kaiser Permanente Medical Center in Oakland, California.
      The performance of each test and of a combination test (HemeSelect to confirm
      positive Hemoccult II Sensa results) was evaluated by identifying screened
      patients who had colorectal neoplasma (carcinoma or a polyp > or = 1 cm in
      diameter) in the two years after screening. RESULTS: Of the 10,702 eligible
      patients, 8104 (75.7 percent) had at least one interpretable sample and were
      screened on the basis of at least one test; 96 percent of these patients had
      complete two-year follow-up. The sensitivity of the tests for detecting carcinoma
      was lowest with Hemoccult II (37.1 percent; 95 percent confidence interval, 19.7
      to 54.6 percent), intermediate with the combination test (65.6 percent; 95
      percent confidence interval, 47.6 to 83.6 percent) and with HemeSelect (68.8
      percent; 95 percent confidence interval, 51.1 to 86.4 percent), and highest with
      Hemoccult II Sensa (79.4 percent; 95 percent confidence interval, 64.3 to 94.5
      percent). The specificity for detecting carcinoma was 86.7 percent with Hemoccult
      II Sensa, 94.4 percent with HemeSelect, 97.3 percent with the combination test,
      and 97.7 percent with Hemoccult II. HemeSelect and the combination test detected
      more colorectal carcinomas and polyps than Hemoccult II, with only slight
      increases in the number of colonoscopies needed. CONCLUSIONS: HemeSelect and a
      combination test in which HemeSelect is used to confirm positive Hemoccult II
      Sensa results improve on Hemoccult II in screening patients for colorectal
      carcinoma.

PMID- 8531972
TI  - Images in clinical medicine. Paget's disease of bone.

PMID- 8531973
TI  - Compensation to a department of medicine and its faculty members for the teaching
      of medical students and house staff.
AB  - BACKGROUND: Changes in the organization and financing of health care threaten to
      alter the prevailing system of financing the teaching of medical students and
      residents. Little information is available from private medical schools and
      teaching hospitals about the extent of teaching by faculty members or the
      mechanisms and levels of reimbursement for teaching. METHODS: We surveyed faculty
      members in the Department of Medicine at Columbia-Presbyterian Medical Center to
      ascertain the extent of their teaching activities. A standard number of hours was
      assigned to each activity, and the total number of teaching hours was calculated
      for each faculty member. Teaching of fellows and in continuing medical education
      programs was excluded. We also determined how much money the Department of
      Medicine received in payment for faculty members' teaching activities, and the
      sources of this compensation. RESULTS: In the 1992-1993 academic year, the 188
      full-time faculty members spent a total of 46,086 hours teaching (mean [+/- SD],
      245 +/- 178 hours per faculty member); 10,780 hours (23.4 percent) were spent
      teaching medical students, and 35,306 hours (76.6 percent) teaching house staff.
      Eighty percent of faculty members taught for 137 or more hours each. In a
      multivariate analysis including faculty rank, subspecialty division, years since
      graduation from medical school, sex, and tenure or clinical track, senior faculty
      members (P = 0.02), members of certain subspecialty divisions (P < 0.001), and
      women (P = 0.05) contributed more than the average number of teaching hours. An
      additional 56 non-full-time faculty members contributed a total of 5684 hours.
      The net reimbursement to the department for teaching totaled $965,808, or about
      $16 per hour of teaching by full-time faculty members, after the cost of fringe
      benefits was excluded. CONCLUSIONS: Faculty members of the department of medicine
      at a major medical center contribute a large number of hours teaching medical
      students and house staff. This effort is poorly compensated. Cost-containment
      efforts have the potential to jeopardize fragile social contracts at academic
      health centers whereby the faculty participates in teaching by contributing
      unreimbursed or underreimbursed time.

PMID- 8531974
TI  - Antiepileptic drugs.

PMID- 8531975
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 2-1996. A 32-year-old woman with subcostal pain and a left
      hepatic mass.

PMID- 8531976
TI  - Tribulations and rewards of academic medicine--where does teaching fit?

PMID- 8531978
TI  - Improving the fecal occult-blood test.

PMID- 8531977
TI  - BRCA1--lots of mutations, lots of dilemmas.

PMID- 8531979
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531980
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531981
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531982
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531983
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531984
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531985
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531986
TI  - The attack on the National Center for Injury Prevention and Control.

PMID- 8531987
TI  - Regional variation across the United States in the management of acute myocardial
      infarction.

PMID- 8531988
TI  - Regional variation across the United States in the management of acute myocardial
      infarction.

PMID- 8531989
TI  - Bacterial pneumonia in HIV.

PMID- 8531990
TI  - Hepatitis G infection in drug abusers with chronic hepatitis C.

PMID- 8531991
TI  - Doctors and the criminal law.

PMID- 8531992
TI  - Case records of the Massachusetts General Hospital: a home-court advantage?

PMID- 8531993
TI  - Case records of the Massachusetts General Hospital: a home-court advantage?

PMID- 8531994
TI  - Case records of the Massachusetts General Hospital: a home-court advantage?

PMID- 8531995
TI  - Politics and public health.

PMID- 8531996
TI  - Direct cultivation of the causative agent of human granulocytic ehrlichiosis.
AB  - BACKGROUND: Human granulocytic ehrlichiosis is a potentially fatal tick-borne
      infection that has recently been described. This acute febrile illness is
      characterized by myalgias, headache, thrombocytopenia, and elevated serum
      aminotransferase levels. The disease is difficult to diagnose because the
      symptoms are non-specific, intraleukocytic inclusions (morulae) may not be seen,
      and the serologic results are often initially negative. Little is known about the
      causative agent because it has never been cultivated. METHODS: We studied three
      patients with symptoms and laboratory findings suggestive of human granulocytic
      ehrlichiosis, including unexplained fever after probable exposure to ticks,
      granulocytopenia, and thrombocytopenia. Peripheral blood was examined for
      ehrlichia microscopically and with use of the polymerase chain reaction (PCR).
      Blood was inoculated into cultures of HL60 cells (a line of human promyelocytic
      leukemia cells), and the cultures were monitored for infection by Giemsa staining
      and PCR. RESULTS: Blood from the three patients, only one of whom had inclusions
      suggestive of ehrlichia in neutrophils, was positive for human granulocytic
      ehrlichiosis on PCR. Blood from all three patients was inoculated into HL60 cell
      cultures and caused infection, with intracellular organisms visualized as early
      as 5 days after inoculation and cell lysis occurring within 12 to 14 days. The
      identity of the cultured organisms was confirmed by immunofluorescence
      microscopy, PCR analysis, and DNA sequencing. DNA from the infected cells was
      sequenced in regions of the 16S ribosomal gene reported to differ between the
      agent of human granulocytic ehrlichiosis and closely related species, including
      Ehrlichia equi and E. phagocytophila which cause infection in animals. The
      sequences from all three human isolates were identical and differed from the
      strain of E. equi studied in having guanine rather than adenine at nucleotide 84.
      CONCLUSIONS: We describe the cultivation of the agent of human granulocytic
      ehrlichiosis in cell culture. The ability to isolate this organism should lead to
      a better understanding of the biology, treatment, and epidemiology of this
      emerging infection.

PMID- 8531997
TI  - Coronary bypass surgery with internal-thoracic-artery grafts--effects on survival
      over a 15-year period.
AB  - BACKGROUND: Aortocoronary bypass surgery has been performed most often with the
      patient's saphenous vein as the conduit. The internal-thoracic-artery graft,
      which has superior patency rates, has been shown to have clinical advantages, but
      it is not known how long these advantages persist. METHODS: We identified all the
      patients in the registry of the Coronary Artery Surgery Study who had undergone
      first-time coronary-artery bypass grafting. Those with internal-thoracic-artery
      bypass grafts (749 patients) were compared with those with saphenous-vein bypass
      grafts only (4888 patients) with respect to survival over a 15-year follow-up
      period. RESULTS: In a multivariate analysis to account for differences between
      the two groups, the presence of an internal-thoracic-artery graft was an
      independent predictor of improved survival and was associated with a relative
      risk of dying of 0.73 (95 percent confidence interval, 0.64 to 0.83). This
      improved survival was also observed in subgroups including patients 65 years of
      age or older, both men and women, and patients with impaired ventricular
      function. The survival curves of the two groups showed further separation over
      the years of follow-up, with a more marked downsloping after eight years in the
      curve for the group with saphenous-vein grafts only than in that for the group
      with internal-thoracic-artery grafts. CONCLUSIONS: As compared with saphenous
      vein coronary bypass grafts, internal-thoracic-artery grafts conferred a survival
      advantage throughout a 15-year follow-up period. The survival advantage increased
      with time, suggesting that the initial selection of the conduit was a more
      important factor in survival than problems appearing long after surgery, such as
      the progression of coronary disease.

PMID- 8531998
TI  - Lack of effect of thyroxine in patients with Graves' hyperthyroidism who are
      treated with an antithyroid drug.
AB  - BACKGROUND: Antithyroid drugs are effective in patients with hyperthyroidism due
      to Graves' disease, but the rate of recurrence after treatment is high. In a
      recent Japanese study, adjunctive treatment with thyroxine (T4) was associated
      with a recurrence rate 20 times lower than that among patients who received only
      an antithyroid drug. If these results are confirmed, combined therapy with an
      antithyroid drug and T4 might become the treatment of choice for all patients
      with Graves' hyperthyroidism. METHODS: We treated 111 patients (89 women and 22
      men) who had Graves' hyperthyroidism. All patients initially received 40 mg of
      carbimazole daily for one month. Then one group received carbimazole alone for 17
      months (52 patients), and the other group received carbimazole plus T4 for 17
      months and T4 alone for 18 months (59 patients). In the carbimazole group, the
      dose was adjusted after one month to maintain a normal serum thyrotropin
      concentration. In the carbimazole-T4 group, the dose of carbimazole was not
      changed, but 100 micrograms of T4 per day was added to the regimen and the dose
      was adjusted to maintain an undetectable serum thyrotropin concentration (< 0.04
      microU per milliliter). RESULTS: At the time of our analysis, 53 of the 111
      patients had completed at least 3 months of follow-up (median, 12 months) after
      carbimazole was withdrawn. Hyperthyroidism recurred in eight patients in each
      group after a mean (+/- SD) of 6 +/- 4 months in the carbimazole group and 7 +/-
      4 months in the carbimazole-T4 group. There was no difference between the
      recurrence rates in the two groups, despite the fact that serum thyrotropin
      concentrations were undetectable in 73 percent of patients in the carbimazole-T4
      group on at least 75 percent of their visits. CONCLUSIONS: The administration of
      T4 to patients with Graves' disease during carbimazole treatment and after its
      withdrawal neither delays nor prevents the recurrence of hyperthyroidism.

PMID- 8531999
TI  - Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients
      with neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is a childhood tumor derived from cells of the neural
      crest, with a widely variable outcome. Differences in the behavior and prognosis
      of the tumor suggest that neuroblastoma can be divided into several biologic
      subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma
      to determine their prognostic value. METHODS: We used Southern blot analysis to
      study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of
      chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas.
      We also determined the nuclear DNA content of the tumor cells. RESULTS: Allelic
      loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q
      were significantly associated with unfavorable outcome. In a multivariate
      analysis, loss of chromosome 1p was the most powerful prognostic factor. It
      provided strong prognostic information when it was included in multivariate
      models containing the prognostic factors of age and stage or serum ferritin level
      and stage. Among the patients with stage I, II, or IVS disease, the mean (+/- SD)
      three-year event-free survival was 100 percent in those without allelic loss of
      chromosome 1p and 34 +/- 15 percent in those with such loss; the rates of three
      year event-free survival among the patients with stage III and stage IV disease
      were 53 +/- 10 percent and 0 percent, respectively. CONCLUSIONS: The loss of
      chromosome 1p is a strong prognostic factor in patients with neuroblastoma,
      independently of age and stage. It reliably identifies patients at high risk in
      stages I, II, and IVS, which are otherwise clinically favorable. More intensive
      therapy may be considered in these patients. Patients in stages III and IV with
      allelic loss of chromosome 1p have a very poor outlook, whereas those without
      such loss are at moderate risk.

PMID- 8532000
TI  - Expression of the gene for multidrug-resistance-associated protein and outcome in
      patients with neuroblastoma.
AB  - BACKGROUND: Overexpression of the gene for the multidrug-resistance-associated
      protein (MRP) has been linked with resistance to chemotherapeutic agents
      (multidrug resistance) in vitro. The expression of MRP by neuroblastoma cells
      correlates with N-myc oncogene amplification, a well-established prognostic
      indicator in patients with neuroblastoma. METHODS: To relate MRP gene expression
      to established prognostic markers and the clinical outcome of neuroblastoma, we
      analyzed MRP expression in specimens of primary tumors from 60 patients with
      neuroblastoma. RESULTS: Levels of MRP gene expression were significantly higher
      in tumors with N-myc amplification than in tumors without such amplification (P <
      0.001). High levels of MRP expression were strongly associated with reductions in
      both survival and event-free survival (P < 0.001) in the overall study population
      and in subgroups of patients without N-myc amplification and patients with
      localized disease. For the overall study population, the five-year cumulative
      survival rates in the groups with high and low levels of MRP expression were 57
      percent (95 percent confidence interval, 37 to 78 percent) and 94 percent (95
      percent confidence interval, 86 to 100 percent), respectively. In contrast,
      expression of the MDR1 multi-drug-resistance gene was not predictive of survival
      or event-free survival. After adjustment by multivariate analysis for the effects
      of N-myc amplification and other prognostic indicators, high levels of MRP
      expression retained significant prognostic value for poor survival (relative
      hazard, 14.9; P = 0.01) and poor event-free survival (relative hazard, 9.7; P =
      0.004), whereas N-myc amplification had no prognostic value. CONCLUSIONS: High
      levels of MRP gene expression in patients with neuroblastoma correlate strongly
      with poor outcome. The findings suggest that expression of this multidrug
      resistance gene accounts for the association between N-myc amplification and
      reduced survival.

PMID- 8532001
TI  - Images in clinical medicine. Nail in the aorta.

PMID- 8532002
TI  - Streptococcal infections of skin and soft tissues.

PMID- 8532003
TI  - Octreotide.

PMID- 8532004
TI  - Case records of the Massachusetts General Hospital. Case 3-1996. Severe abdominal
      pain during early pregnancy in a woman with previous infertility.

PMID- 8532005
TI  - Ehrlichiosis--in pursuit of an emerging infection.

PMID- 8532006
TI  - Internal-thoracic-artery grafts. Biologically better coronary arteries.

PMID- 8532007
TI  - Immunosuppression of Graves' hyperthyroidism--still an elusive goal.

PMID- 8532008
TI  - Multidrug-resistant tuberculosis.

PMID- 8532009
TI  - Multidrug-resistant tuberculosis.

PMID- 8532010
TI  - Multidrug-resistant tuberculosis.

PMID- 8532011
TI  - Efficacy of metformin in non-insulin-dependent diabetes mellitus.

PMID- 8532012
TI  - Efficacy of metformin in non-insulin-dependent diabetes mellitus.

PMID- 8532013
TI  - Mitochondrial DNA and disease.

PMID- 8532014
TI  - Mitochondrial DNA and disease.

PMID- 8532015
TI  - Hematopoietic reconstitution with autologous stem cells.

PMID- 8532017
TI  - Ehrlichia infection as a cause of severe respiratory distress.

PMID- 8532016
TI  - Body-cavity-based lymphoma in an HIV-seronegative patient without Kaposi's
      sarcoma-associated herpesvirus-like DNA sequences.

PMID- 8532018
TI  - Surveillance for rheumatic fever.

PMID- 8532019
TI  - Recovered memories.

PMID- 8532020
TI  - Recovered memories.

PMID- 8532021
TI  - Recovered memories.

PMID- 8532022
TI  - Mismatches of minor histocompatibility antigens between HLA-identical donors and
      recipients and the development of graft-versus-host disease after bone marrow
      transplantation.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) can be a major complication of
      allogeneic bone marrow transplantation even when the donor and recipient are
      siblings and share identical major histocompatibility antigens. The explanation
      may be a mismatch of minor histocompatibility antigens. We previously
      characterized five minor histocompatibility antigens, HA-1, 2, 3, 4, and 5, that
      are recognized by T cells in association with the major histocompatibility
      antigens HLA-A1 an A2. METHODS: We collected peripheral-blood leukocytes from 148
      bone marrow recipients and their sibling donors, who were genotypically HLA
      identical. Fifty pairs were positive for HLA-A1, 117 were positive for HLA-A2,
      and 19 were positive for both. The pairs were typed with cytotoxic-T-cell clones
      specific for minor histocompatibility antigens HA-1, 2, 3, 4, and 5. RESULTS:
      Mismatches of HA-3 were equally distributed among recipients in whom GVHD
      developed and those in whom it did not. By contrast, a mismatch of only HA-1 was
      significantly correlated with GVHD of grade II or higher (odds ratio, infinity; P
      = 0.02) in adults. One or more mismatches of HA-1, 2, 4, and 5 were also
      significantly associated with GVHD (odds ratio, infinity; P = 0.006) in adults.
      These associations were not observed in children. CONCLUSIONS: A mismatch of
      minor histocompatibility antigen HA-1 can cause GVHD in adult recipients of
      allogeneic bone marrow from HLA-identical donors. Prospective HA-1 typing may
      improve donor selection and identify recipients who are at high risk for GVHD.

PMID- 8532023
TI  - Polymorphism of adhesion molecule CD31 and its role in acute graft-versus-host
      disease.
AB  - BACKGROUND: Graft-versus-host disease (GVHD) caused by poorly defined minor
      (i.e., other than HLA) histocompatibility antigens remains a serious problem in
      recipients of bone marrow transplants. We sought to determine whether the CD31
      adhesion molecule is a minor alloantigen. METHODS: We directly sequenced samples
      of complementary DNA (cDNA) encoding CD31 molecules from 21 unrelated normal
      subjects. Sequence-specific primers were then designed to amplify alleles by the
      polymerase chain reaction, thereby permitting CD31 typing of genomic DNA from
      additional normal subjects. To assess the relevance of CD31 matching to bone
      marrow transplantation, we performed CD31 typing of 46 recipients of bone marrow
      (32 without GVHD and 14 with severe [grade III or IV] acute GVHD) and their HLA
      identical sibling donors. The immunoreactivity of CD31 phenotypes with anti-CD31
      monoclonal antibodies was compared by flow cytometry. RESULTS: Direct sequencing
      of cDNA for CD31 from the 21 normal subjects identified a single polymorphism,
      CTG-->GTG (Leu-->Val), at codon 125; we designated the resulting alleles CD31.L
      and CD31.V, respectively. The CD31 genotypes of these and 142 other unrelated
      subjects were of the expected frequencies. Among the transplant recipients, 71
      percent of those with acute GVHD had CD31 genotypes that were not identical to
      the donor's genotype, as compared with 22 percent of the recipients without GVHD
      (P = 0.004). The binding of anti-CD31 monoclonal antibodies as measured by
      fluorescence-activated cell sorting correlated with the CD31 types of homozygous
      cell lines. CONCLUSIONS: The adhesion molecule CD31 is polymorphic. When donor
      and recipient genotypes are not identical, the risk of GVHD increases.
      Prospective CD31 typing may reduce the risk of acute GVHD.

PMID- 8532024
TI  - Serum immunoreactive-leptin concentrations in normal-weight and obese humans.
AB  - BACKGROUND: Leptin, the product of the ob gene, is a hormone secreted by
      adipocytes. Animals with mutations in the ob gene are obese and lose weight when
      given leptin, but little is known about the physiologic actions of leptin in
      humans. METHODS: Using a newly developed radioimmunoassay, wer measured serum
      concentrations of leptin in 136 normal-weight subjects and 139 obese subjects
      (body-mass index, > or = 27.3 for men and > or = 27.8 for women; the body-mass
      index was defined as the weight in kilograms divided by the square of the height
      in meters). The measurements were repeated in seven obese subjects after weight
      loss and during maintenance of the lower weight. The ob messenger RNA (mRNA)
      content of adipocytes was determined in 27 normal-weight and 27 obese subjects.
      RESULTS: The mean (+/- SD) serum leptin concentrations were 31.3 +/- 24.1 ng per
      milliliter in the obese subjects and 7.5 +/- 9.3 ng per milliliter in the normal
      weight subjects (P < 0.001). There was a strong positive correlation between
      serum leptin concentrations and the percentage of body fat (r = 0.85, P < 0.001).
      The ob mRNA content of adipocytes was about twice as high in the obese subjects
      as in the normal-weight subjects (P < 0.001) and was correlated with the
      percentage of body fat (r = 0.68, P < 0.001) in the 54 subjects in whom it was
      measured. In the seven obese subjects studied after weight loss, both serum
      leptin concentrations and ob mRNA content of adipocytes declined, but these
      measures increased again during the maintenance of the lower weight. CONCLUSIONS:
      Serum leptin concentrations are correlated with the percentage of body fat,
      suggesting that most obese persons are insensitive to endogenous leptin
      production.

PMID- 8532026
TI  - Images in clinical medicine. Dilatation of the pulmonary arteries in primary
      pulmonary hypertension.

PMID- 8532025
TI  - A comparison of continuous intravenous epoprostenol (prostacyclin) with
      conventional therapy for primary pulmonary hypertension.
AB  - BACKGROUND: Primary pulmonary hypertension is a progressive disease for which no
      treatment has been shown in a prospective, randomized trial to improve survival.
      METHODS: We conducted a 12-week prospective, randomized, multicenter open trial
      comparing the effects of the continuous intravenous infusion of epoprostenol
      (formerly called prostacyclin) plus conventional therapy with those of
      conventional therapy alone in 81 patients with severe primary pulmonary
      hypertension (New York Heart Association functional class III or IV). RESULTS:
      Exercise capacity was improved in the 41 patients treated with epoprostenol
      (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base
      line), but it decreased in the 40 patients treated with conventional therapy
      alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of
      the treatment groups). Indexes of the quality of life were improved only in the
      epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the
      epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for
      the epoprostenol and control groups were -8 percent and +3 percent, respectively
      (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to 
      2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for
      the epoprostenol and control groups were -21 percent and +9 percent, respectively
      (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval,
      -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study,
      all of whom had been randomly assigned to conventional therapy (P = 0.003).
      Serious complications included four episodes of catheter-related sepsis and one
      thrombotic event. CONCLUSIONS: As compared with conventional therapy, the
      continuous intravenous infusion of epoprostenol produced symptomatic and
      hemodynamic improvement, as well as improved survival in patients with severe
      primary pulmonary hypertension.

PMID- 8532027
TI  - Attitudes of Michigan physicians and the public toward legalizing physician
      assisted suicide and voluntary euthanasia.
AB  - BACKGROUND: There has been a continuing public debate about assisted suicide and
      the proper role, if any, of physicians in this practice. Legislative bans and
      various forms of legalization have been proposed. METHODS: We mailed
      questionnaires to three stratified random samples of Michigan physicians in
      specialties likely to involve the care of terminally ill patients: 500 in the
      spring of 1994, 500 in the summer of 1994, and 600 in the spring of 1995. Similar
      questionnaires were mailed to stratified random samples of Michigan adults: 449
      in the spring of 1994 and 899 in the summer of 1994. Several different
      questionnaire forms were used, all of which included questions about whether
      physician-assisted suicide should be banned in Michigan or legalized under
      certain conditions. RESULTS: Usable questionnaires were returned by 1119 of 1518
      physicians eligible for the study (74 percent), and 998 of 1307 eligible adults
      in the sample of the general public (76 percent). Asked to choose between
      legalization of physician-assisted suicide and an explicit ban, 56 percent of
      physicians and 66 percent of the public support legalization, 37 percent of
      physicians and 26 percent of the public preferred a ban, and 8 percent of each
      group were uncertain. When the physicians were given a wider range of choices, 40
      percent preferred legalization, 37 percent preferred "no law" (i.e., no
      government regulation), 17 percent favored prohibition, and 5 percent were
      uncertain. If physician-assisted suicide were legal, 35 percent of physicians
      said they might participate if requested--22 percent would participate in either
      assisted suicide or voluntary euthanasia, and 13 percent would participate only
      in assisted suicide. Support for physician-assisted suicide was lowest among the
      strongly religious. CONCLUSIONS: Most Michigan physicians prefer either the
      legalization of physician-assisted suicide or no law at all; fewer than one fifth
      prefer a complete ban on the practice. Given a choice between legalization and a
      ban, two thirds of the Michigan public prefer legalization and one quarter prefer
      a ban.

PMID- 8532028
TI  - Legalizing assisted suicide--views of physicians in Oregon.
AB  - BACKGROUND: Since the Oregon Death with Dignity Act was passed in November 1994,
      physicians in Oregon have faced the prospect of legalized physician-assisted
      suicide. We studied the attitudes and current practices of Oregon physicians in
      relation to assisted suicide. METHODS: From March to June 1995, we conducted a
      cross-sectional mailed survey of all physicians who might be eligible to
      prescribe a lethal dose of medication if the Oregon law is upheld. Physicians
      were asked to complete and return a confidential 56-item questionnaire. RESULTS:
      Of the 3944 eligible physicians who received the questionnaire, 2761 (70 percent)
      responded. Sixty percent of the respondents thought physician-assisted suicide
      should be legal in some cases, and nearly half (46 percent) might be willing to
      prescribe a lethal dose of medication if it were legal to do so; 31 percent of
      the respondents would be unwilling to do so on moral grounds. Twenty-one percent
      of the respondents have previously received requests for assisted suicide, and 7
      percent have complied. Half the respondents were not sure what to prescribe for
      this purpose, and 83 percent cited financial pressure as a possible reason for
      such requests. The respondents also expressed concern about complications of
      suicide attempts and doubts about their ability to predict survival at six months
      accurately. CONCLUSIONS: Oregon physicians have a more favorable attitude toward
      legalized physician-assisted suicide, are more willing to participate, and are
      currently participating in greater numbers than other surveyed groups of
      physicians in the United States. A sizable minority of physicians in Oregon
      objects to legalization and participation on moral grounds. Regardless of their
      attitudes, physicians had a number of reservations about the practical
      applications of the act.

PMID- 8532029
TI  - Antisense-oligonucleotide therapy.

PMID- 8532030
TI  - Clinical problem-solving. A broken heart.

PMID- 8532031
TI  - Minor histocompatibility antigens and marrow transplantation.

PMID- 8532032
TI  - Obesity, leptin, and the brain.

PMID- 8532033
TI  - Euthanasia in Australia--the Northern Territory Rights of the Terminally Ill Act.

PMID- 8532034
TI  - Outcomes and costs of care for acute low back pain.

PMID- 8532035
TI  - Outcomes and costs of care for acute low back pain.

PMID- 8532036
TI  - Outcomes and costs of care for acute low back pain.

PMID- 8532037
TI  - Outcomes and costs of care for acute low back pain.

PMID- 8532038
TI  - Hereditary hemorrhagic telangiectasia.

PMID- 8532039
TI  - Hereditary hemorrhagic telangiectasia.

PMID- 8532040
TI  - Gene therapy.

PMID- 8532041
TI  - Gene therapy.

PMID- 8532042
TI  - Hydroxyurea in sickle cell disease.

PMID- 8532043
TI  - Hydroxyurea in sickle cell disease.

PMID- 8532044
TI  - Tuberculosis in a neighborhood bar.

PMID- 8532045
TI  - Healing by design.

PMID- 8532046
TI  - Healing by design.

PMID- 8532048
TI  - Storage fungi and seed health of rice: a study in the Philippines.
AB  - Fifty seed samples of different rice varieties stored in warehouses for varying
      periods (1-28 months) were collected and screened for their fungal flora, using
      standard blotter and agar plate methods, resulting in the isolation of 36 fungal
      forms. The samples were also studied for moisture content, germinability, and
      seedling abnormalities. Significant correlations were found among the numbers of
      fungi, storage period, and germinability. Fourteen samples, seven each of IR64
      and IR66 were studied with regard to moisture content, germination test, abnormal
      seedlings, speed of germination, conductance of leachates, total dehydrogenase
      activity, total free amino acids, total soluble sugar, fat acidity,
      gelatinization temperature, gel consistency, amylose content, translucency, and
      per cent whiteness. Significant relationships were found between the fungi and
      the parameters studied.

PMID- 8532047
TI  - Occurrence of Penicillium marneffei infections among wild bamboo rats in
      Thailand.
AB  - Penicilliosis marneffei has emerged as an endemic systemic mycosis in Southeast
      Asia among humans and wild bamboo rats. To gain an insight into the epidemiology
      of this life-threatening disease, a survey of bamboo rats for natural infections
      by Penicillium marneffei was carried out in the central plains of Thailand during
      June-September, 1987. Thirty-one lesser bamboo rats (Cannomys badius) and eight
      hoary bamboo rats (Rhizomys pruinosus) were trapped. Portions of their internal
      organs were cultured to determine if they had been infected by P. marneffei. Six
      each of C. badius (19.4%) and R. pruinosus (75%) yielded cultures of this unique,
      dimorphic Penicillium species. All of the isolates were readily converted to
      their unicellular form that multiplies by the process of schizogony by incubating
      them at 37 degrees C on plates of brain heart infusion agar. Their identity was
      further confirmed by a specific immunological test. Among the internal organs of
      the positive rats, the lungs had the highest positivity (83.3%), next in
      decreased order of frequency were the liver (33.3%) and the pancreas (33.3%). The
      use and value of domestic and wild animals in locating and demarcating endemic
      areas of geophilic fungal pathogens are discussed. Penicilliosis marneffei is
      considered to be a zooanthroponosis--a disease that occurs in lower animals, as
      well as, humans.

PMID- 8532049
TI  - Fertility of Fusarium moniliforme from maize and sorghum related to fumonisin
      production in Italy.
AB  - Forty-three strains of Fusarium moniliforme isolated from infected maize and
      sorghum plants in Italy were assayed for their ability to produce fertile crosses
      with "A" and "F" mating population tester strains, in relation to their ability
      to produce fumonisins on maize substrate. Most of the strains isolated from maize
      (ear and stalk rot and maize-based feed), producing fumonisin B1 (FB1) and B2
      (FB2) (up to 4,100 and 855 mg/kg, respectively), belonged to the "A" mating
      population. All of the strains isolated from sorghum belonged to the "F" mating
      population and produced little or no FB1 and FB2. This is the first report of the
      occurrence of mating population "F" in Europe. Our data on strains from Italy are
      consistent with previous studies from the United States that found significant
      differences in sexual fertility and fumonisin production between strains from
      maize and sorghum.

PMID- 8532050
TI  - Occurrence of mycotoxins in cereals and animal feedstuffs in Natal, South Africa
      1994.
AB  - During the year of 1994, 417 samples of agricultural commodities, comprising:
      maize, compound animal feeds, oil seeds, soya bean, fish meal and forage were
      examined for fungi and over 20 mycotoxins using a multi-screen augmented with
      individual assays. Trichothecenes had the highest incidence of over 19% in all
      samples received, followed by aflatoxin at 6% and then zearalenone at 3%.
      Selected samples (73) were analyzed for fumonisin B1 and of these, 69 (94%) were
      found to be positive. Because of this result and high incidence of Fusarium spp.
      (over 70%) in maize and maize containing feeds, which was higher than either
      Aspergillus spp. (19%) or Penicillium spp. (33%), attention is drawn to the
      actual and potential presence of fumonisin in the food chain.

PMID- 8532051
TI  - A case of cutaneous phaeohyphomycosis caused by Exserohilum rostratum, its in
      vitro sensitivity and review of literature.
AB  - A 40 year old woman presented with the infection of skin of 3 years duration on
      the upper anterior aspect of fore-arm. Histologic examination of the skin tissue
      revealed dematiaceous hyphae, aggregated structures or single celled elements. On
      detailed mycological examination the isolate was identified as Exserohilum
      rostratum. Among the antimycotic tested in vitro amorolfine was found to be most
      effective with MIC value of 3 mcg/ml. This is the first report of E. rostratum
      infection of man from India.

PMID- 8532052
TI  - Western blot analysis of cerebrospinal fluid for detection of Aspergillus
      antigens.
AB  - Western-blot immunoassay of cerebrospinal fluid (CSF) specimens of patients with
      central nervous system (CNS) aspergillosis (3), CNS candidosis (1) and bacterial
      meningitis (2) was carried out using pooled serum from histopathologically proven
      deep-seated aspergillosis cases to detect unique antigenic fractions for
      aspergillosis in CSF. No reactivity was observed in patients with non-fungal
      meningitis. Four cross-reactive bands (40, 90, 200 and > 200 KD) were detectable
      in CSF from patients with both aspergillosis and candidosis of the CNS. Four
      additional bands (90-200 KD) were consistently present only in patients with
      aspergillosis. One prominent band (110 KD) was found only in the patient with
      aspergillosis who had a fatal outcome and raised the possibility of being a poor
      prognostic marker.

PMID- 8532053
TI  - Intensive hemodialysis and hemoperfusion treatment of Amanita mushroom poisoning.
AB  - Over a period of fifteen years, 41 patients including 23 males and 18 females
      with Amanita mushroom poisoning were treated at the University Hospital of Lund,
      Sweden. The intensity of poisoning was graded according to serum transaminase
      elevations and prothrombin time reductions. Severity was mild in 16 patients
      (Group A), moderate in 14 (Group B) and severe in 11 (Group C). Members of Group
      C reported shorter latency periods before the onset of symptoms, (10 +/- 1 hours,
      P < 0.05) and longer delays in treatment, (34 +/- 4 hours), than did the other
      patients. Intensive treatment was begun before the results of urine amatoxin
      assay were reported. Treatment consisted of: fluid and electrolyte replacement,
      oral activated charcoal and lactulose, i.v. penicillin, combined hemodialysis and
      hemoperfusion in two 8 hour sessions, some received i.v. thioctic acid, other
      i.v. silibinin, all received a special diet. This combination of treatment
      modalities was used to accelerate the elimination of amatoxin from the patients'
      bodies. The longest period of hospitalization, 13 +/- 2 days, was required by the
      patients of Group C (p < 0.01). All patients improved and were discharged from
      the hospital asymptomatic. No sequelae were later reported for the majority of
      those moderately and severely poisoned. We have concluded that intensive combined
      treatment applied in these cases is effective in relieving patients with both
      moderate and severe amanitin poisoning.

PMID- 8532054
TI  - Expression of elastinolytic activity among isolates in Aspergillus section flavi.
AB  - A survey of the distribution of elastinolytic potential among 32 culture
      collection isolates of Aspergillus flavus. A. oryzae, A. parasiticus, A. sojae,
      A. nomius, and A. tamarii revealed this character to be highly conserved within
      Aspergillus Section Flavi. Furthermore, 144 isolates of A. flavus from
      environmental samples from six separate regions of the United States produced
      elastase on solid medium. Most previously described polymorphisms in
      elastinolytic potential were attributed to the toxicity of borate buffers.
      Replacement of borate with HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic
      acid) resulted in detection of elastase production on solid medium by all tested
      fungal isolates except two that had been in culture over 50 years. In liquid
      culture, only isolates of A. flavus, A. tamarii, and A. oryzae accumulated
      elastase activity. Although isoelectric focusing revealed only one isoform (pI
      9.0) of elastase in these culture filtrates, elastinolytic activity in filtrates
      was partially inhibited by both 1,10-phenanthrolene (2 mM) and
      phenylmethylsulfonylfluoride (2 mM), suggesting the presence of both metallo and
      serine elastinolytic proteinases.

PMID- 8532055
TI  - Ochratoxin A and aflatoxins in breast milk samples from Sierra Leone.
AB  - Breast milk from 113 mothers in two 'Under-Five Clinics' in the Southern Province
      of Sierra Leone, namely, Njala and Bo, were examined for their mycotoxin content.
      Only 10 were mycotoxin-free. Eighty-eight per cent of samples contained various
      aflatoxins and 35% contained ochratoxin A (OTA). Few samples (15%) had a single
      mycotoxin. Thirty-six (32%) had two mycotoxins and 50 (40%) had three or more.
      The occurrence of OTA in combination with various aflatoxins was recorded. It is
      concluded that infants in Sierra Leone are exposed to OTA and aflatoxins at
      levels which in some cases far exceed those permissible in animal feed in
      developed countries.

PMID- 8532056
TI  - Mitochondrial DNA analysis of Exophiala spinifera.
AB  - Restriction fragment length polymorphism (RFLP) of mitochondrial DNA (mtDNA) was
      examined in 36 isolates of Exophiala spinifera (8 isolates from Brazil, 9 from
      China, 15 from Columbia, 1 from the United States and 2 from Venezuela). E.
      spinifera isolates displayed a high degree of mtDNA diversity in RFLP patterns
      and were clustered into six genetically heterogeneous groups (Group 1 through
      Group 6). Isolates of Group 2 including the type strain seemed to have a
      worldwide distribution. RFLP patterns of E. spinifera were also distinct from
      those of other dematiaceous fungi, such as E. jeanselmei, E. moniliae, E.
      dermatitidis, Fonsecaea pedrosoi, Cladosporium carrionii and Phialophora
      verrucosa. These results indicate that E. spinifera may be a taxonomic complex
      and that RFLP patterns will be useful in the identification, typing and
      epidemiology of the E. spinifera variants.

PMID- 8532057
TI  - Association of hypersensitivity and carriage of dermatophytes in clinically
      normal sites in patients with Tinea cruris.
AB  - Forty nine patients with mycologically confirmed Tinea cruris were investigated
      for the association of hypersensitivity to trichophytin and the isolation of
      dermatophytes from clinically normal sites with chronicity and recurrence of
      infection. At the end of six months following specific therapy, 24 patients
      returned for follow up and they were similarly studied. Dermatophytes were
      isolated from clinically asymptomatic sites in 46% patients before treatment and
      in 21% of the patients on follow up. Immediate weal reaction and increased
      concentration of IgE antibodies were seen in 73% and 80% of the patients
      respectively. However, the delayed hypersensitivity reaction was more associated
      with patients having lesions for more than 6 months (48%) in comparison with
      patients with a short history (17%). On follow up after 6 months, the different
      hypersensitivity reactions and IgE antibody concentration maintained more or less
      the same association. Therefore in persistent or recurrent Tinea cruris
      infection, besides potential carriage in clinically normal sites,
      hypersensitivity to antigens of dermatophytes possibly plays an important role in
      pathogenicity.

PMID- 8532058
TI  - Biochemical, antigenic and allergenic characterization of crude extracts of
      Drechslera (Helminthosporium) monoceras.
AB  - In a previous study with airborne mould extracts we verified that Drechslera
      (Helminthosporium) monoceras presented stronger reactions than those presented by
      42 other moulds isolated in Sao Paulo city. In the present study, we evaluated
      the biochemical composition and the antigenicity of crude extracts obtained from
      vegetative and conidial stage of D. monoceras using Czapeck broth (CB) modified
      and tris-HCl for extraction. The maximum values of total proteins and lipids were
      verified in the crude extract obtained in the 28th day of growth, and maximum
      values of carbohydrates were observed in the extracts of the 16th, 22nd and 26th
      days. The fractionated proteins by SDS-PAGE presented bands with molecular
      weights between 14.4 to 67 Kd; the 28th day extract showed a larger number of
      bands. The carbohydrates and amino acids were characterized by thin-layer
      chromatography. The antigenicity of the crude extracts was verified by
      immunodiffusion reaction in agar against rabbit hyperimmune sera. Precipitation
      lines were observed in all studied extracts and common antigenic molecular
      populations. Based on the above results, the 28th day extract was selected to
      verify the induction of IgE antibody responses in immunizations of Balb/c and cAF
      1 mice, and titer by passive cutaneous anaphylaxis test using Wistar rats. The
      maximum titers obtained were 160 in cAF-1 mice and 1.280 in Balb/c mice. The
      results suggest that the 28th day extract contains allergenic fractions and
      should be chosen for future studies related to fractionation, characterization
      and standardization in diagnostic methods and immunotherapy.

PMID- 8532059
TI  - Acremonium kiliense peritonitis complicating continuous ambulatory peritoneal
      dialysis: report of two cases.
AB  - Two cases of peritonitis caused by Acremonium kiliense in patients receiving a
      continuous ambulatory peritoneal dialysis treatment are reported. Diagnosis was
      established by direct examination and cultures of dialysis effluent, secretion of
      catheter-exit-site and from the tip of the catheter. Management of fungal
      peritonitis includes catheter removal, since in this infection the result of
      systemic antifungal therapy is inconsistent.

PMID- 8532060
TI  - Cytologic findings in 43 cases of blastomycosis diagnosed ante-mortem in
      naturally-infected dogs.
AB  - A retrospective study of the cytology of blastomycosis was undertaken. Sixty-one
      samples from 43 naturally infected dogs diagnosed ante-mortem by means of
      cytology were reviewed. Skin and lymph nodes rendered the highest number of
      positive samples with 17 out of 18 and 14 out of 17 respectively. Transtracheal
      washes contained the tissue forms of Blastomyces dermatitidis in 3 out of 5
      samples. Pyogranulomatous inflammation was diagnosed in 38 of the 61 samples, and
      of these, 25 cases contained multinucleated giant cells. Epithelioid cells were
      found in all 38 cases. Purulent inflammation was seen in 15 out of 61 samples.
      Three cases had a minimal or virtual lack of inflammation. The cytologic findings
      are described and photographically illustrated.

PMID- 8532061
TI  - Influence of carbon and nitrogen sources on glutathione catabolic enzymes in
      Candida albicans during dimorphism.
AB  - The effect of carbon sources, glucose and sucrose, and nitrogen sources such as
      ammonia, glutamate and L-citrulline on the activities of glutathione metabolic
      enzymes has been studied. Yeast and mycelial cells were used to identify changes
      in activity levels of glutathione reductase (GSSGR), glutathione transferase
      (GST), glutathione peroxidase (GPX) and gamma-glutamyl transpeptidase (GGT).
      Enzyme activities from cells grown in sucrose media were lower than in glucose
      media regardless of the enzyme tested, morphological form, or the growth
      interval. In all enzymes except GST, activity was higher in yeast form than in
      mycelia, regardless of nitrogen source, with lower activity from 24 to 72 h than
      at 96 h. In citrulline media, yeast form showed the maximum GST, GGT, and GPX
      activity. In ammonia-amended media, mycelia showed maximum activity in GGT,
      whereas in glutamate media, mycelia showed the maximum activity in GST. Also, the
      type of nitrogen source had no effect on GPX activity in the mycelial form.
      Finally, changing the nitrogen source showed no significant effect on GSSGR
      activity, either in the yeast or mycelial form.

PMID- 8532062
TI  - Prevalence of Candida ciferrii in elderly patients with trophic disorders of the
      legs.
AB  - In order to define the prevalence of Candida ciferrii in onychomycosis, the
      fungal biota associated with toe nail onyxis was examined in 50 elderly patients
      with trophic disorders of the legs and in 220 patients without clinical evidence
      of trophic disorders. Candida ciferrii was more frequent in the first group of
      patients since it was recovered from 24% of these patients, whereas its
      prevalence was only 1.4% in the control group. Moreover, the positivity of the
      direct examination of toe nail scrapings, the absence of any other associated
      pathogens, and the repeated isolation of this yeast species for some of the
      patients confirmed its pathogenicity.

PMID- 8532064
TI  - Subtype specificity of gamma-aminobutyric acid type A receptor antagonism by
      clozapine.
AB  - Clozapine, an atypical neuroleptic, functionally antagonizes the gamma
      aminobutyric acid-induced chloride uptake via the main central inhibitory
      receptor, gamma-aminobutyric acid type A (GABAA) receptor, in brain vesicles.
      GABAA antagonism by micromolar concentrations of clozapine is more efficient in
      rat cerebrocortical and hippocampal membranes than in cerebellar membranes, as
      evidenced by clozapine reversal GABA-inhibition of [35S]t
      butylbicyclophosphorothionate ([35S]TBPS) binding. A typical neuroleptic,
      haloperidol, failed to antagonize GABA in any of these brain regions, while the
      specific GABAA antagonist 2'-(3'-carboxy-2',3'-propyl)-3-amino-6-p 
      methoxyphenylpyrazinium bromide (SR 95531) was efficient in all three brain
      regions. Clozapine action on [35S]TBPS binding was unaffected by the
      benzodiazepine receptor antagonist flumazenil. Clozapine inhibited the binding of
      [3H]muscimol and [3H]SR 95531 to the GABA recognition site, but this effect only
      partially correlated with the regional differences in and the potency of
      clozapine antagonism of GABA-inhibition of [35S]TBPS binding, suggesting that
      also other than GABA sites may mediate clozapine actions. Autoradiography of
      [35S]TBPS binding revealed GABA antagonism by clozapine in most brain regions.
      Main exceptions were cerebellar granule cell and molecular layers, olfactory bulb
      external plexiform and glomerular layers and primary olfactory cortex, where
      clozapine antagonized GABA inhibition less than average, and lateral hypothalamic
      and preoptic areas where its antagonism was greater than average. Recombinant
      alpha 6 beta 2 gamma 2 receptors, the predominant alpha 6 subunit-containing
      receptor subtype in cerebellar granule cells, failed to show GABA antagonism by
      clozapine up to 100 microM. In contrast, recombinant alpha 1 beta 2 gamma 2
      receptors, forming the predominant receptor subtype in the brain, were clozapine
      sensitive. Recombinant alpha 6 beta 2 gamma 2 and alpha 6 beta 3 gamma 2
      receptors resulted in clozapine-insensitive receptors, whereas alpha 6 beta 1
      gamma 2 receptors were clozapine sensitive. The efficacy of clozapine to
      antagonize GABA in alpha 1 beta x gamma 2 receptors decreased in the order of
      alpha 1 beta 1 gamma 2 > alpha 1 beta 2 gamma 2> alpha 1 beta 3 gamma 2. The
      results indicate that clozapine antagonizes the function of most GABAA receptor
      subtypes, and that the interaction is determined by the interaction of the alpha
      and beta subunit variants. GABA antagonism is a unique property of clozapine, not
      shared by haloperidol, which might be involved in the pharmacological mechanism
      for the increased seizure susceptibility associated with clozapine treatment.

PMID- 8532063
TI  - Nitric oxide synthase: expression and expressional control of the three isoforms.
AB  - Three isozymes of nitric oxide synthase (NOS) have been identified. Their cDNA-
      and protein structures as well as their genomic DNA structures have been
      described. NOS I (ncNOS, originally discovered in neurons) and NOS III (ecNOS,
      originally discovered in endothelial cells) are low output, Ca(2+)-activated
      enzymes whose physiological function is signal transduction. NOS II (iNOS,
      originally discovered in cytokine-induced macrophages) is a high output enzyme
      which produces toxic amounts of NO that represent an important component of the
      antimicrobial, antiparasitic and antineoplastic activity of these cells.
      Depending on the species, NOS II activity is largely (human) or completely (mouse
      and rat) Ca(2+)-independent. In the human species, the NOS isoforms I, II and III
      are encoded by three different genes located on chromosomes 12, 17 and 7,
      respectively. The amino acid sequences of the three human isozymes (deduced from
      the cloned cDNAs) show less than 59% identity. Across species, amino acid
      sequences are more than 90% conserved for NOS I and III, and greater 80%
      identical for NOS II. All NOS produce NO by oxidizing a guanidino nitrogen of L
      arginine utilizing molecular oxygen and NADPH as co-substrates. All isoforms
      contain FAD, FMN and heme iron as prosthetic groups and require the cofactor BH4.
      NOS I and III are constitutively expressed in various cells. Nevertheless,
      expression of these isoforms is subject to regulation. Expression is enhanced by
      e.g. estrogens (for NOS I and III), shear stress, TGF-beta 1, and (in certain
      endothelial cells) high glucose (for NOS III). TNF-alpha reduces the expression
      of NOS III by a post-transcriptional mechanism destabilizing the mRNA. The
      regulation of the NOS I expression seems to be very complex as reflected by at
      least 8 different promoters transcribing 8 different exon 1 sequences which are
      expressed differently in different cell types. Expression of NOS II is mainly
      regulated at the transcriptional level and can be induced in many cell types with
      suitable agents such as LPS, cytokines, and other compounds. Whether some cells
      can express NOS II constitutively is still under debate. Pathways resulting in
      the induction of the NOS II promoter may vary in different cells. Activation of
      transcription factor NF-kappa B seems to be an essential step for NOS II
      induction in most cells. The induction of NOS II can be inhibited by a wide
      variety of immunomodulatory compounds acting at the transcriptional levels and/or
      post-transcriptionally.

PMID- 8532066
TI  - Patch clamp study of histamine activated potassium currents on rabbit olfactory
      bulb neurons.
AB  - Effects of histamine, histamine agonists and antagonists on steady state current
      in principal neurons and interneurons were investigated in thin slices from the
      olfactory bulb of newborn rabbits with the nystatin perforated patch-clamp
      technique and local pipette application. No change in steady state current was
      observed in mitral cells. In most of the periglomerular, juxtaglomerular and
      granular cells, however, H1-receptor activation caused an outward current; a
      similar effect, but mostly not on the same neurons was elicited by 8-bromo-cyclic
      AMP. These currents were reversed at the potassium equilibrium potential,
      indicating block of a potassium current. Specific H3-receptor activation and
      cyclic GMP were ineffective. Histamine usually caused a combined effect beginning
      with an inward current. Histaminergic neurons fire with changes in behavioural
      state and can, by the described mechanisms, markedly influence signal processing
      in the olfactory bulb.

PMID- 8532065
TI  - Ritanserin potentiates the stimulatory effects of raclopride on neuronal activity
      and dopamine release selectivity in the mesolimbic dopaminergic system.
AB  - The atypical profile of clozapine and some other new antipsychotic drugs has been
      attributed to a relatively selective effect on the mesolimbic dopaminergic
      system, as well as to their potent serotonin 5-HT2 receptor antagonism and high
      ratio of 5-HT2 to dopamine D2 receptor affinities. It is unclear, however, how
      concurrent 5-HT2 and D2 receptor antagonism specifically affects the
      mesoaccumbens and the mesocortical dopaminergic systems. The present study
      examined the effect of pretreatment with the 5-HT2 receptor antagonist,
      ritanserin, on changes in midbrain dopamine neuronal activity as well as in
      forebrain, extracellular concentrations of dopamine, induced by relatively low
      doses of the D2 receptor antagonist raclopride, utilizing in vivo extracellular
      single cell recording techniques and voltammetry in anesthetized rats, as well as
      microdialysis in freely moving rats. Raclopride alone (10-2560 microgram/kg,
      i.v.) induced a dose-dependent increase in three parameters of neuronal activity,
      i.e. burst firing, firing rate and variation coefficient, of midbrain DA neurons.
      This effect of raclopride was more pronounced in cells of the ventral tegmental
      area than in cells of the substantia nigra-zona compacta. Ritanserin alone (1.0
      mg/kg, i.v.) also increased all three parameters of neuronal activity in dopamine
      cells of the ventral tegmental area, but only firing rate in the cells of the
      substantia nigra. Ritanserin pretreatment (30 min) significantly enhanced the
      stimulatory effects of low doses of raclopride (10-20 micrograms/kg, s.c.)
      increased extracellular concentrations of dopamine in the medial prefrontal
      cortex and the dorsolateral striatum by 75 and 110%, respectively, as measured by
      microdialysis. Ritanserin alone (1.5 mg/kg, s.c.) did not significantly affect
      cortical and striatal extracellular dopamine concentrations; however,
      pretreatment (40 min) with ritanserin elevated the raclopride-induced increase of
      dopamine concentrations in the medial prefrontal cortex of about 250%, but failed
      to affect the action of raclopride on striatal dopamine levels. Raclopride alone
      (10 and 320 micrograms/kg, i.v.) dose-dependently increased extracellular
      concentrations of dopamine in the nucleus accumbens and the dorsolateral striatum
      to about 500%, as determined by voltammetry. Ritanserin alone (1.0 mg/kg, i.v.)
      did not significantly affect the voltammetric dopamine signal in the nucleus
      accumbens or the dorsolateral striatum; however, ritanserin pretreatment (30 min)
      enhanced the raclopride-induced increase in accumbal but not striatal dopamine
      concentrations to about 1600%. The stimulatory effect of the combined ritanserin
      plus raclopride treatment on neuronal activity and DA release was more pronounced
      in the mesolimbic than the nigrostriatal dopaminergic system. The present data
      indicate that concurrent 5-HT2 and D2 receptor antagonism selectively affects the
      activity of the mesolimbic dopaminergic system. These findings provide an
      experimental basis for the notion that combined 5-HT2 and D2 receptor antagonism
      may underlie the limbic mode of action of at least some atypical antipsychotic
      drugs and consequently contribute to their unique therapeutic effects.

PMID- 8532067
TI  - Stimulation of serotonin release in the rat brain cortex by activation of
      ionotropic glutamate receptors and its modulation via alpha 2-heteroreceptors.
AB  - Rat brain cortex slices were used to study (1) the release of 5-hydroxytryptamine
      (5-HT) induced by activation of N-methyl-D-aspartate (NMDA) or non-NMDA receptors
      and (2) the alpha 2-adrenoceptor-mediated modulation of NMDA-evoked 5-HT release.
      Cortical slices were preincubated with [3H]5-HT in the presence of the selective
      noradrenaline uptake inhibitor, maprotiline (to avoid false labelling of
      noradrenergic axon terminals), and the superfused with solution containing the 5
      HT reuptake inhibitor, 6-nitroquipazine. In slices superfused with Mg(2+)-free
      medium, NMDA and L-glutamate, in a concentration-dependent manner, elicited an
      overflow of tritium. The NMDA-evoked tritium overflow was abolished by omission
      of Ca2+ ions, almost completely suppressed by 1.2 mM Mg2+ and only partly (by
      about 60%) inhibited by tetrodotoxin. Dizocilpine (formerly MK-801), an
      antagonist at the phencyclidine site within the NMDA-gated channel, also
      decreased the NMDA-evoked overflow. The competitive NMDA receptor antagonist DL
      (E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) caused a parallel
      shift of the NMDA concentration-response curve to the right. The NMDA-induced
      tritium overflow was not affected by addition of exogenous glycine but was
      inhibited by 5,7-dichlorokynurenic acid, an antagonist at the glycine site of the
      NMDA receptor. Spermidine slightly increased the NMDA-induced tritium overflow
      whereas arcaine, an antagonist at the polyamine site of the NMDA-receptor, caused
      a decrease. Ifenprodil and eliprodil, which exhibit different affinities for NMDA
      receptors composed of different subunits were highly potent (in the nanomolar
      range) in inhibiting the NMDA-evoked tritium overflow. Noradrenaline reduced,
      whereas the alpha 2-adrenoceptor antagonist idazoxan facilitated, the NMDA-evoked
      overflow. Idazoxan shifted the concentration-response curve of noradrenaline to
      the right. In slices superfused with solution containing 1.2 mM Mg2+, kainic acid
      or (RS)-alpha-amino-3-hydroxy-5-methyl-4 -isoxazole propionic acid (AMPA) also
      caused a concentration-dependent overflow of tritium, which again was not
      completely (by about 75 and 50%, respectively) inhibited by tetrodotoxin. The
      kainate-evoked tritium overflow was inhibited by the non-NMDA receptor antagonist
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not affected by CGP 37849 or
      arcaine. The AMPA-evoked tritium overflow was also decreased by CNQX. It is
      concluded that activation of NMDA or non-NMDA receptors elicits a release of 5-HT
      in the rat brain cortex. The receptors are at least partly located on the
      serotoninergic nerve terminals. The results with ifenprodil and eliprodil are
      compatible with the view that the NMDA receptor involved contains the NR2B
      subunit. The NMDA-evoked 5-HT release is modulated by presynaptic alpha 2
      adrenoceptors.

PMID- 8532068
TI  - Somatostatin receptors mediating inhibition of basal and stimulated electrogenic
      ion transport in rat isolated distal colonic mucosa.
AB  - The aim of this study was to examine the potencies of several recently identified
      selective somatostatin (SRIF)-receptor ligands as inhibitors of electrogenic ion
      transport in the rat distal colonic mucosa with the view to identifying the SRIF
      receptor type involved. Under basal conditions, cumulative administration of SRIF
      and SRIF28 decreased short circuit current (SCC), a measure of electrogenic ion
      transport, with EC50 values of 4 nM and 9 nM respectively. The peptidase
      inhibitors, phosphoramidon (1 microM) and amastatin (10 microM), has no effect on
      the potencies of either SRIF or SRIF28. The inhibitory action of SRIF on basal
      SCC was suppressed by piretanide and diphenylamine-2-carboxylate, compatible with
      the assumption that the Na+K+2Cl- co-transporter and Cl- channels, respectively,
      may be involved in this antisecretory action of SRIF. Tetrodotoxin (1 microM) had
      no effect on the antisecretory action of SRIF, suggesting that the process was
      not neuronally mediated. All of the SRIF analogues examined, with the exception
      of BIM-23056, maximally inhibited basal SCC to a similar extent as SRIF.
      Seglitide and octreotide were both more potent antisecretory agents than SRIF
      (respective EC50 values, 0.4 nM and 1.5 nM) suggesting that this effect was
      mediated by a receptor belonging to the SRIF1 receptor group. The most
      distinguishing feature of the rank order of agonist potencies was the high
      potency of the selective sst2 receptor ligand, BIM-23027 (EC50 value 0.32 nM),
      the weaker potency exhibited by the selective sst5 receptor ligand, L-362855
      (EC50 value 21 nM), and the lack of agonist activity displayed by the selective
      sst3 receptor ligand, BIM-23056 (EC50 value > 1000 nM). This profile is
      comparable with that observed in binding studies on the recombinant sst2
      receptor. Forskolin-stimulated secretion was suppressed by SRIF analogues with
      the rank order of agonist potencies BIM-23027 > SRIF > L-362855 >> BIM-23056
      which resembled that exhibited under basal conditions. However, the absolute
      potencies of these agonists were lower (respective EC50 values 2 nM, 14 nM< 38 nM
      and > 1000 nM) whilst the magnitude of inhibition was about three fold greater.
      BIM-23027 and SRIF (both 30 nM) also inhibited carbachol-stimulated increases in
      basal SCC by 60-70%, while a similar concentration of L-362855 inhibited these
      responses by 11%. BIM-23056 (1 microM) had no effect on carbachol-simulated
      secretion. Radioligand binding studies on rat colonic mucosal membranes using
      [125I]-Tyr11-SRIF suggested heterogeneity of SRIF binding sites. Thus, SRIF and
      SRIF28 competed for binding (IC50 values, 0.32 and 0.63 nM, respectively) with
      Hill slopes less than unity; while seglitide and BIM-23027 both maximally
      displaced only 30-40% of specific binding with apparent high affinity (respective
      pIC50 values, 10.1 nM and 10.0). In conclusion, SRIF decreases basal as well as
      both cAMP and Ca(2+)-dependent Cl- secretion in rat colonic mucosa. The rank
      order of agonist potencies suggests that receptors resembling the recombinant
      sst2 receptor mediate inhibition of basal and forskolin-stimulated secretion.
      Radioligand binding studies suggest that BIM-23027 interacts with a sub
      population of [125I]Tyr11-SRIF binding sites in rat colonic mucosal membranes
      which probably corresponds to the receptors mediating the antisecretory effects
      described here.

PMID- 8532069
TI  - Vasodilatation produced by adenosine in isolated rat perfused mesenteric artery:
      a role for endothelium.
AB  - Adenosine and adenosine triphosphate (ATP) induced vasodilatation was studied in
      isolated rat perfused mesenteric artery at constant flow. Decrease in perfusion
      pressure was measured after induction of tone by continuous infusion with
      phenylephrine (5-7 microM). Adenosine and ATP caused dose-dependent vasodilation.
      Following infusion with selective A2 adenosine receptor antagonist, 3,7-dimethyl
      1-propargylxanthine (DMPX) (10 microM), or non-selective adenosine receptor
      antagonist, theophylline (30 microM), vasodilation produced by adenosine were
      significantly reduced at lower doses. Responses to adenosine were not affected by
      pretreatment of tissues with either the P2-purinoceptor desensitizing agent,
      alpha, beta methylene ATP (30 microM), or the P2-purinoceptor antagonist, suramin
      (10 microM). In contrast, both alpha, beta methylene ATP and suramin
      significantly attenuate relaxation produced by ATP. Further, it was found that
      relaxation elicited by either adenosine or ATP was not significantly affected by
      the presence of glibenclamide (30 microM). Vasodilatation induced by adenosine
      and ATP was greatly reduced in denuded arteries but more so for ATP than
      adenosine. It is concluded that adenosine-mediated vasodilatation may hardly be
      due to the stimulation of A2 adenosine receptors and is strongly dependent on the
      presence of functional endothelium whereas ATP-mediated vasodilator responses
      were mediated via the activation of P2-purinoceptors and appeared to be entirely
      dependent upon the presence of functional endothelium. Further, vasodilator
      responses to neither adenosine nor ATP were sensitive to inhibition by the
      potassium channel blocker glibenclamide, in isolated mesenteric perfused bed.
      This would imply that ATP-sensitive potassium channels were not involved in
      adenosine and ATP mediated vasodilatation.

PMID- 8532070
TI  - Bombesin-induced contractions of guinea pig lung strips are modulated by
      endogenous nitric oxide.
AB  - We have investigated the effects of a nitric oxide (NO) biosynthesis inhibitor N
      omega-nitro-L-arginine methyl ester (L-NAME) on the bombesin-evoked contraction
      of guinea pig parenchymal lung strips. The bombesin-induced contractions of lung
      strips were significantly increased after L-NAME (300 micro)) pre-treatment. The
      maximal response was increased (P < 0.01) by 37% after L-NAME treatment when
      compared with the control group. The pD2 value was not influenced by L-NAME pre
      treatment. The enhancement of the bombesin-induced contraction caused by L-NAME
      was reversed by addition of an excess of the NO precursor L-arginine (600 microM)
      but not by the addition of its inactive enantiomer D-arginine (600 microM). Like
      L-NAME, methylene blue (1 microM), an agent that inhibits the soluble guanylyl
      cyclase activated by NO, significantly increased (P < 0.01) the maximal
      contraction induced by bombesin (183 +/- 16 mg) when compared with the control
      group (141 +/- 15 mg). When tested against other agonist-induced contractions, L
      NAME did not change the responsiveness of parenchymal lung strips to bradykinin
      or carbachol but significantly increased lung contraction induced by histamine.
      NO synthesis inhibition resulted in a pronounced increase in the bombesin-induced
      contraction of guinea-pig lung strips. Our results suggest that bombesin
      contributes to NO synthesis and release which then acts to reduce the contraction
      of the lungstrip in response to bombesin.

PMID- 8532071
TI  - Etofibrate suppresses neointima formation of the ballooned common carotid artery
      of rats.
AB  - The inhibition of neointima formation by drugs is a major goal to prevent
      restenosis following angioplasty. In the present study, the effect of etofibrate
      on blood lipids and vessels wall was investigated using a balloon injury rat
      model. Two weeks after ballooning the common carotid artery neointima formation
      was quantified by morphometric measurement of the neointimal area and cellularity
      in vessel cross sections, and by fluorometric evaluation of the DNA content.
      Etofibrate (160 mg/kg/day) had no effect on plasma triglyceride levels, but
      reduced serum cholesterol by about 25%. The injury-induced increase of both the
      neointimal area and the DNA-content was significantly inhibited by 47% (P <
      0.005) and 34% (P < 0.05), respectively, in the drug-treated animals in
      comparison to the untreated control rats. The ratio of neointima and media was
      significantly (P < 0.001) reduced from 152.9 +/- 11.6% (controls) to 82.84 +/-
      12.59% in the etofibrate-treated group. The cellularity (numerical profile and
      volume density of nuclei) in the neointima was similar in both groups. In
      conclusion, injury-induced neointima formation is reduced in etofibrate-treated
      animals, which could be due to an inhibition of smooth muscle cell proliferation.

PMID- 8532072
TI  - Dose-dependent separation of dopaminergic and adrenergic effects of epinine in
      healthy volunteers.
AB  - Epinine (N-methyl-dopamine, the active metabolite of ibopamine), is a full
      agonist at dopamine (DA)-receptors and alpha- and beta-adrenoceptors. To study
      whether in vivo DA-receptors mediated effects can be separated from alpha- and
      beta-adrenoceptor effects we compared in 10 male volunteers the effects of i.v.
      epinine (0.5; 1; 2; 4 micrograms/kg/min for 15 min each) on DA-receptor (changes
      in serum prolactin)- and alpha- and beta-adrenoceptor (changes in systolic
      [Psyst] and diastolic blood pressure [Pdiast] and heart rate)-mediated effects
      with those of dopamine before and after propranolol (5 mg i.v. 45 min pre
      infusion), bisoprolol (15 mg p.o. 2 h pre-infusion) and domperidone (10 mg p.o. 1
      h pre-infusion). At the 0.5 and 1 microgram doses of dopamine and epinine did not
      effect Psyst, Pdiast and heart rate but significantly decreased prolactin levels.
      At the higher dose both dopamine and epinine significantly increased Psyst and
      heart rate, while only epinine significantly increased Pdiast. In addition, both
      dopamine and epinine significantly increased diuresis and natriuresis; in
      contrast, only dopamine, but not epinine dose-dependently increased plasma
      noradrenaline levels. Domperidone did not affect dopamine- and epinine-evoked
      blood pressure- and heart rate-changes, but antagonized their prolactin-effects
      (at least at the lower doses). Bisoprolol and propranolol significantly reduced
      dopamine-induced Psyst- and heart rate-increases to about the same extent.
      Propranolol enhanced epinine-induced Psyst- and Pdiast-increases while bisoprolol
      reduced epinine-evoked Psyst-increase but not Pdiast-increase. Epinine-induced
      heart rate-increase was abolished by bisoprolol and was converted into heart rate
      decrease by propranolol. We concluded that in 0.5 and 1 microgram doses (plasma
      levels of 20-80 nmol/l)epinine acts only at DA-receptors. Thus, ibopamine in
      therapeutically recommended doses (3 x 100 mg/day with peak plasma epinine-levels
      of 50-80 nmol/l) very likely activates only DA-receptors. In higher doses,
      however, epinine-like dopamine-activates alpha- and beta-adrenoceptors whereby
      epinine has a stronger alpha-adrenoceptor agonistic activity than dopamine.
      Moreover, part of the dopamine-effects are indirect via release of endogenous
      noradrenaline whereas epinine-effects do not appear to include an indirect
      component.

PMID- 8532074
TI  - Hypersensitive response of malignant hyperthermia-susceptible skeletal muscle to
      inositol 1,4,5-triphosphate induced release of calcium.
AB  - Malignant hyperthermia (MH) is associated with abnormal regulation of
      intracellular calcium in skeletal muscle fibers. Besides a mutation in the
      ryanodine receptor gene, an increase in inositol, 1,4,5-triphosphate (InsP3)
      levels could be a possible candidate for the abnormal regulation of intracellular
      calcium. However, the effect of InsP3 on [Ca2+]i in MH is not known.
      Microinjection of InsP3 increased intracellular Ca2+ in intact skeletal muscle
      from malignant hyperthermia susceptible swines (MHS) with a higher potency and
      efficacy than in muscles from nonsusceptible (MHN) swines. Omission of
      extracellular Ca2+ or incubation of muscle fibers with Ca2+ channel blockers did
      not modify the response to InsP3. However, dantrolene (50 microM) a known blocker
      of intracellular Ca2+ release, decreased resting intracellular Ca2+ concentration
      and prevented the InsP3-induced increase in intracellular Ca2+. This suggests (i)
      that MHS skeletal muscles exhibit a higher responsiveness to InsP3-induced
      release of Ca2+, which could implicate InsP3 in the pathophysiology of MH, and
      (ii) that the beneficial effect of dantrolene in MHS could be related to its
      ability to prevent the InsP3-induced release of Ca2+.

PMID- 8532073
TI  - Theophylline kinetics in peripheral tissues in vivo in humans.
AB  - Several biochemical and cellular effects have been described for methylxanthines
      under in vitro conditions. However, it is unknown, whether threshold
      concentrations required to exert these effects are attained in target tissues in
      vivo. We therefore employed the microdialysis technique for measuring
      theophylline concentrations in peripheral tissues under in vivo conditions.
      Following in vitro and in vivo calibration, microdialysis probes were inserted
      into the medial vastus muscle and into the periumbilical subcutaneous adipose
      layer of healthy volunteers. Following single oral dose administration of 300 mg
      or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline
      concentrations were monitored in tissues and plasma. Major pharmacokinetic
      parameters (cmax, tmax, AUC) were calculated for plasma and tissue time courses.
      The mean AUCtissue/AUCplasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and
      0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue. We conclude that
      microdialysis provides important information on the distribution and the tissue
      pharmacokinetics of theophylline.

PMID- 8532075
TI  - Cultured chick sympathetic neurons: prostanoid EP1 receptor-mediated facilitation
      of noradrenaline release.
AB  - Prostanoid EP receptor-mediated modulation of noradrenaline release from cultured
      chick sympathetic neurons was investigated. Transmitter release from dissociated
      cell cultures of embryonic paravertebral ganglia, loaded with [3H]-noradrenaline,
      was elicited either by electrical field stimulation (36 pulses/3 Hz) or by
      elevating the extracellular concentration of K+ (to 30 mM; for 2 min).
      Prostaglandin E2 (PGE2; 0.01-3 microM) enhanced electrically evoked [3H]
      noradrenaline release in a concentration-dependent manner with a maximal increase
      by about 50% at 1 microM. Also iloprost (0.1-3 microM) increased transmitter
      release concentration- dependently, whereas misoprostol (0.1-3 microM) had no
      effect. Indometacin (10 microM) influenced neither evoked release per se nor the
      enhancement caused by PGE2- AH6809 (3 microM), a selective EP1 receptor
      antagonist, blocked the enhancement caused by both PGE2 and iloprost K(+)-evoked
      noradrenaline release, which was virtually insensitive to tetrodotoxin (0.3
      microM), was increased by PGE2 to an extent comparable to that observed after
      electrical stimulation. In summary, the present data indicate that PGE2
      facilitates noradrenaline release from cultured chick sympathetic neurons by a
      receptor which shows the pharmacological profile of the EP1 subtype and is
      probably located at the processes of the neuron.

PMID- 8532076
TI  - Subclassification of presynaptic 5-HT autoreceptors in the human cerebral cortex
      as 5-HT1D receptors.
AB  - Human cerebral cortical synaptosomes were used to determine the 5
      hydroxytryptamine (5-HT) receptor subtype to which the inhibitory presynaptic 5
      HT autoreceptor belongs. The synaptosomes preincubated with [3H]5-HT were
      superfused and tritium overflow was stimulated by high K+. The K(+)-evoked
      tritium overflow, which was Ca(2+)-dependent but tetrodotoxin-resistant, was
      concentration-dependently inhibited by the nonselective 5-HT 1D alpha/1D beta
      receptor agonist, 5-carboxamidotryptamine. Ketanserin at a concentration which
      should block the 5-HT 1D alpha but not the 5-HT 1D beta receptor failed to
      antagonize the inhibitory effect of 5-carboxamidotryptamine. In contrast, the
      nonselective 5-HT 1D alpha/1D beta receptor antagonist, methiothepin, at a
      concentration which should block both the 5-HT 1D alpha and the 5-HT 1D beta
      receptor abolished the effect of 5-carboxamidotryptamine. It is concluded that
      the presynaptic 5-HT autoreceptor, which has previously been classified as 5-HT
      1D, belongs to the 5-HT1D beta subtype.

PMID- 8532077
TI  - Binding properties of the naturally occurring human 5-HT1A receptor variant with
      the Ile28Val substitution in the extracellular domain.
AB  - The cDNA from a schizophrenic patient heterozygous for a mutation of the 5-HT1A
      receptor gene was used to clone the variant and wild-type DNA into a eukaryotic
      expression vector. The mutation was characterized by a base pair substitution (A 
      -> G) at the first position of codon 28, leading to an Ile --> Val amino acid
      exchange. COS-7 cells were transfected with the cDNA of either the wild type or
      the variant 5-HT1A receptor. The potencies of the 5-HT1A receptor agonists 8
      hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT), 5-HT and roxindole, and of
      the antagonists methiothepin and spiperone in inhibiting specific binding of
      [3H]8-OH-DPAT of the mutant and wild-type 5-HT1A receptor ligands concentration
      dependently inhibited specific [3H]8-OH-DPAT binding to both the wild-type and
      the variant 5-HT1A receptor. The rank order of potency of the ligands in
      inhibiting [3H]8-OH-DPAT binding was identical at both receptors and was
      roxindole > 8-OH-DPAT > 5-HT> methiothepin > spiperone. This rank order is
      characteristic for 5-HT1A receptors. The negative logarithms of the
      concentrations required for 50% inhibition (pIC50 values) of the ligands at the
      mutant 5-HT receptor correlated highly significantly with those at the wildtype
      receptor (r = 0.995). It is concluded that the pharmacological profile of the
      mutant 5-HT1A receptor does not differ from that of the wild-type 5-HT1A
      receptor.

PMID- 8532078
TI  - [Altitude illness].

PMID- 8532079
TI  - [Discipline-advice medicine 1994].

PMID- 8532080
TI  - [100 years of radiology in The Netherlands. VII. 200 years protection against
      roentgen irradiation?].

PMID- 8532081
TI  - [100 years of radiology in The Netherlands. VIII. Radiology in dentistry].

PMID- 8532082
TI  - [100 years of radiology in the Netherlands. IX. Clinical radiobiology].

PMID- 8532083
TI  - [100 years of radiology in The Netherlands. X. Clinical radiation physics].

PMID- 8532084
TI  - [100 years of radiology in The Netherlands. XI. Radiation hygiene in medicine].

PMID- 8532085
TI  - [Multiple pulmonary embolisms in nursing home patients recognizable by alertness
      to certain aspecific symptoms].
AB  - OBJECTIVE: To determine whether increased alertness regarding multiple pulmonary
      embolism in geriatric patients increases the number of cases diagnosed. DESIGN:
      Retrospective descriptive study. SETTING: Dutch nursing homes Marienhaven
      (psychogeriatric) in Warmond and De Wilbert (somatic and psychogeriatric) in
      Katwijk aan den Rijn, the Netherlands. METHOD: In the period 1989-1991, the
      diagnosis of multiple pulmonary embolism was suspected in 15 patients with an
      'unclear' or 'aspecific' complex of symptoms, who subsequently underwent
      ventilation perfusion scintigraphy. RESULTS: In 11/15 patients the diagnosis of
      multiple pulmonary embolism was confirmed. These patients were treated with
      anticoagulants resulting in complete recovery in 9 patients. Aspecific symptoms
      suggestive of pulmonary embolism include subfebrile temperature, respiratory and
      sensory disturbances and a clinical picture mimicking airway infection. If lung
      scintigraphy is only performed if a positive diagnosis will have the
      therapeutical consequences for the patients concerned, and assuming that
      refraining from treatment would lead to death, it was calculated that on a yearly
      basis mortality in subjects in nursing homes could be reduced by more than 2%
      when appropriate diagnosis is made and treatment given. Comparison of the data
      from SIG Health Information (Utrecht) with the present results suggests that the
      prevalence of (multiple) pulmonary embolism in the Dutch nursing homes is
      insufficiently recognized. CONCLUSION: More alertness regarding multiple
      pulmonary embolism in nursing home patients will establish the diagnosis more
      frequently and proper treatment of this condition will lead to a decrease in
      mortality.

PMID- 8532086
TI  - [Compliance with consensus 'Diagnosis pulmonary embolism' in clinical practice].
AB  - OBJECTIVE: Evaluation of clinical management in patients suspected of pulmonary
      embolism as compared with the Dutch consensus for diagnosing pulmonary embolism.
      DESIGN: Retrospective. SETTING: Medical Centre Alkmaar. METHOD: Retrospective
      analysis of clinical management in patients subjected to ventilation-perfusion
      scintigraphy on suspicion of pulmonary embolism. RESULTS: In 55 (24%) of the 225
      patients included a high-probability scan was found, in 68 (30%) a non-high
      probability scan and in 102 (45%) a normal scan. The clinical management in all
      patients with a normal or high-probability scan was according to the consensus.
      In the 68 patients with a non-high-probability scan the consensus was completely
      followed in 16%, partially in 18% and not at all in 66%. CONCLUSION: Clinical
      management of patients with a non-high-probability scan in the vast majority of
      cases was not according to the consensus. The consensus was followed in all
      patients with a normal or high-probability scan.

PMID- 8532087
TI  - [Favorable development of ability to function in patients during admission in a
      geriatric unit of a psychiatric hospital].
AB  - OBJECTIVE: To evaluate the course of the functional ability in daily living
      activities, mobility and faecal and urinary continence, and the interrelationship
      of these features of ability in patients admitted to the geriatric unit of a
      psychiatric hospital (GAPZ). DESIGN: Retrospective. SETTING: Geriatric unit,
      Vincent van Gogh Institute of Psychiatry, Venray, the Netherlands. METHOD:
      Analysis of data obtained from the National Register of Clinical Gerontology from
      SIG Care Information in Utrecht. For all patients discharged in 1992 the level of
      functional ability on admission and discharge was determined and compared, using
      9 variables. RESULTS: During the stay all but one of the functional status
      variables improved significantly: washing of upper and lower body, dressing,
      going to the toilet, eating, urinary (in)continence and mobility (as measured by
      radius of action and assistance needed). Faecal incontinence did not improve. On
      average women functioned more independently than men; however, the improvement in
      functional status was equal for both sexes. There was a hierarchical decline in
      the event of decreased functional ability. This hierarchical relationship was
      more prominent at the time of discharge than at the time of admission.
      CONCLUSION: On average the functional status of the patients evaluated improved
      during their stay in the geriatric unit of the psychiatric hospital. There
      appears to be a hierarchy of changes in aspects of functional condition
      irrespective of the underlying diseases in elderly people.

PMID- 8532089
TI  - [From the library of the Nederlands Tijdschrift voor Geneeskunde: Antoni van
      Leeuwenhoek's correspondence (1632-1723) and microscopy].

PMID- 8532088
TI  - [A patient with acute leukemia and meningitis caused by Staphylococcus
      epidermidis treated with fosfomycin].
AB  - In a 17-year-old male patient with acute lymphoblastic leukaemia, who was being
      treated with chemotherapy, a Staphylococcus epidermidis infection with several
      septicaemias developed during a period of protracted neutropenia. The patient was
      treated with vancomycin and fusidic acid, but blood cultures remained positive.
      The patient also developed staphylococcal meningitis. After the antibiotic
      regimen was supplemented by fosfomycin, the blood cultures became sterile.
      Combination treatment with vancomycin and fosfomycin was continued for two months
      without apparent toxicity. In individual cases of infection with multiresistant
      S. epidermidis fosfomycin may be included in the antibiotic regimen. This is the
      first report of parenteral use of fosfomycin in the Netherlands.

PMID- 8532090
TI  - [100 years of radiology in The Netherlands. XII. 100 years of legislation and
      regulation].

PMID- 8532091
TI  - [Diagnosis of bronchial asthma and chronic obstructive lung disease by the family
      physician].

PMID- 8532092
TI  - [Minor symptoms in family practice; chloasma or 'pregnancy mask'].

PMID- 8532093
TI  - [Expectant management concerning the breast in 5 patients with occult breast
      carcinoma].

PMID- 8532094
TI  - [Treatment and prevention of generalized mycoses].

PMID- 8532095
TI  - [Compliance with psychiatric legal ordinance section 63 STGB. Legal principles-
      current status--treatment concepts--perspectives].
AB  - According to German law, delinquents who are considered either not fully
      responsible or not responsible at all for their actions because of a mental
      disorder receive no punishment or a lesser degree of punishment in criminal
      trials. They may, however, be sentenced to psychiatric treatment either in a
      psychiatric hospital or in an addiction centre, if the risk of them committing
      such offenses in the future is considered to be high. This article reviews the
      current situation of mentally ill offenders in hospitals and explores possible
      developments in forensic psychiatry. It outlines the legal framework, and the
      current and developing treatment strategies, and finally raises the question of
      whether these developments will lead to further specialization of forensic
      psychiatry or to a reintegration of forensic knowledge into general psychiatry.

PMID- 8532096
TI  - [Social legislative and structural deficits of ambulatory management of chronic
      psychiatric and handicapped patients].
AB  - In the past 25 years, psychiatric care for the chronically mentally ill in
      Germany has improved steadily. However, has improved steadily. However, this
      patient group continues to be discriminated against, especially in the sphere of
      outpatient care. The mentally ill often do not meet the requirements that the
      respective social security agencies, i.e. in particular pension and health
      insurance, set out for the granting of benefits. Moreover, contrary to scientific
      knowledge, measures aimed at the treatment of social disabilities are defined not
      as psychiatric rehabilitation measures, but as measures of social integration.
      For these reasons welfare is highly overrepresented in the financing of
      rehabilitation for the mentally ill. In recent years, legislators have attempted
      to compensate certain cases of discrimination. Significant legislative changes
      and administrative developments are described and discussed in terms of their
      implications.

PMID- 8532097
TI  - [Diagnosis and management of neurotic occupational disorders (before pension
      application)].
AB  - This paper summarizes how neurotic disorders affect working capability, with an
      emphasis on neurotic working disorders. According to official statistics neurotic
      disorders account for 5.5% of all disability pensions, but they figure less often
      as diagnoses in medical certificates issued prior to invalidation. The true
      impact of neurotic disorders may only be guessed, since the diagnosis is easy to
      miss and only reluctantly proffered when suspected. In contrast to other neurotic
      disorder afflicting working behaviour, the neurotic working disorder is
      thematically centered within the sphere of work and profession itself. The
      disorder is often treated inadequately and belatedly. Typical somatic complaints
      clusters, characteristic neurotic conflicts and personality traits often
      encountered with neurotic working disorder are outlined. Diagnosis requires the
      taking of a psychobiographic history and some knowledge of psycho- and
      soziotherapy. There are many options for therapy, and there are a few studies
      evaluating their efficacy. In order to install treatment early, a routine checkup
      by a psychotherapist is suggested for all patients exceeding a certain number of
      days off work per year.

PMID- 8532098
TI  - [The Mannheim long-term study of schizophrenia. Initial results of follow-up of
      the illness over 14 years after initial inpatient treatment].
AB  - A 14-year follow-up was accomplished on 56 out of a total of 70 patients first
      admitted to hospital with Schneiderian first-rank symptoms. Data collected during
      5 years after index admission were also at our disposal. Three quarters of the
      probands are living alone, and barely one third are in regular employment. At the
      time of the 14-year follow-up about one third showed delusions or hallucinations.
      Almost the same number had psychological impairments and 64% were socially
      disabled. Comparison with the data collected at 1 year and 5 years reveals no
      difference in the rates of impairments and symptomatology, but a significant
      increase of social disability.

PMID- 8532099
TI  - [Psychoeducational-psychotherapeutic treatment of schizophrenic patients and
      their caregivers. Results of a 1-year catamnestic study].
AB  - In this study we look into the question of whether, in addition to neuroleptic
      treatment, relapse rates among schizophrenic patients can be reduced by means of
      a combined psychoeducational and psychotherapeutic intervention strategy for
      patients and their relatives. In a randomized controlled intervention study in an
      outpatient routine treatment setting, psychoeducational training for medication
      management, cognitive therapy and work with relatives' groups were compared with
      each other and with a control group. The patients continued their standard
      treatment, including neuroleptic relapse prevention. The study comprised 191
      chronic DSM-III-R schizophrenics. Data were collected before and after an 8-month
      intervention phase and at the 1-year follow-up. The group receiving all three
      treatments had the lowest relapse rates. Moreover, numerous gains recorded in
      subjective findings suggest that therapeutic work with schizophrenic patients and
      their relatives is of clinically significant benefit.

PMID- 8532100
TI  - [Psychopharmaceutical drugs in the mass media. Results of a systematic analysis
      of text contents and images].
AB  - Mental diseases and psychopharmacological drugs are frequently discussed in
      newspapers and popular magazines. The representations are supposed to have a
      great impact on people's opinions on the subject. From 1 August 1991 to 31 July
      1992 all articles about psychopharmacological drugs and cardiac drugs in 19
      German newspapers were collected. All statements, effects and side effects, the
      reason for prescription, individual details about the patient and, according to
      this procedure, subjects and implications of the illustrations, were registered
      and classified according to a code book. In contrast to the articles about
      cardiac drugs, half of the psychopharmacological drug reports primarily deal with
      the problems of side effects the drugs may produce. There was much more critical
      comment and emotional emphasis used to characterize the psychopharmacological
      drugs. Only in 9% was their therapeutic efficacy mentioned. Cardiac drugs are
      generally discussed objectively in a medical context and their efficacy is
      emphasized. Psychopharmacological drugs are often mentioned in stories about
      prominent persons having a life crisis, taking drugs, or turning to alcoholism,
      in the sense of social decline. In only 3% of these articles could a serious
      mental diseases be identified as the reason for the prescription. Corresponding
      to the more prominent emotional emphasis of these articles, compared to the
      articles about cardiac drugs, more pictures, mainly of prominent persons or
      patients are used. However, the illustration seldom adds to information provided.
      The reasons for and implications of these findings and the significant
      differences between the distinct groups of newspapers are discussed.

PMID- 8532101
TI  - [Assessment of curriculum by medical students: comparison of participants and non
      participants in voluntary anamnesis groups. An empirical study].
AB  - A representative sample of medical students (n = 121) was given a questionnaire
      to assess parts of their medical education (lectures, seminars, clerkships) and
      to design a subjectively ideal timetable, which was compared with the real
      faculty program. Overall traditional lectures received a low rating (n = 0.17)
      and individual studies with the textbooks a high rating (n = 0.53). The
      information given in programs in psychiatry and psychosomatics in significantly
      less motivating than information to be learned in other medical subjects. This is
      surprising because the ground work for training in the doctor-patient
      relationship should be in these fields. Students with former group experience
      (participation in peer groups on history taking (wish to have more practically
      oriented education compared with the students without group experience. It is not
      clear whether the important factor is participation in group experience before
      starting medical school. (64% of the participants had group experience in the
      first group as opposed to only 45% of the other group). This information should
      be taken into consideration when reforming medical school programs.

PMID- 8532102
TI  - [Psychiatrist--psychiatric critic--"Pazjent". The anti-psychiatry concept of
      Oskar Panizza (1853-1921)].
AB  - Most of the works of the physician and author Dr. med. Oskar Panizza were
      confiscated. Panizza himself was locked up and persecuted because of his works.
      Panizza was a well-educated psychiatrist working with Bernhard von Gudden and
      Emil Kraepelin at the "Oberbairische Kreisirrenanstalt Munchen". When his family
      was afflicted with cases of mental disorders Panizza himself felt threatened from
      insanity. He broke off and became critic of the contemporary psychiatry. He drew
      up a kind of a psychistic psychiatry that anticipated important contents of the
      Anti-psychiatry of the 1970s.

PMID- 8532103
TI  - [Borderline disorder and schizophrenia. Still a diagnostic problem].
AB  - Two case-reports highlight the problems of co-morbidity of schizophrenia and
      borderline disorder. On the other hand, borderline disorder in schizophrenia can
      represent a pre-existent, lasting personality disorder, on the other hand it can
      be temporary syndrome in the course of illness. The assumption that a borderline
      syndrome can be a recompensation stage in the course of schizophrenia seems
      evident by clinical and psychodynamic points of view (concerning a coping
      strategy). The present categories of DSM III-R and ICD-10, however, do not allow
      an adequate diagnostic classification of this syndrome.

PMID- 8532104
TI  - [Clinical evaluation of mentally incompetent patients. Mainz recommendation for
      correction of the drug treatment law].

PMID- 8532105
TI  - Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with
      aging.
AB  - Neonatal Long-Evans rats dosed with TET (5 mg/kg; IP) or saline on postnatal day
      (PND) 10 were examined across the life span for neural damage and performance on
      spatial learning tasks. A subset of rats were sacrificed to assess early damage
      with Nissl-staining, Timm's histochemistry, and glial fibrillary acidic protein
      (GFAP) immunohistochemistry 2, 7, or 14 days after dosing. Littermates were
      tested behaviorally in a T-maze spatial delayed alternation task on PND 23 or PND
      90, and in a Morris water maze place learning task at 3, 12, or 24 months
      postdosing and then sacrificed for histological analysis. In neonatal rats,
      histological analysis indicated gliosis in discrete cortical regions, loss of
      Nissl-stained neurons in the hippocampal formation, entorhinal cortex and
      piriform cortex, and loss of Timm's staining in the entorhinal cortex. The
      behavioral assessment at PND 23 indicated a significant impairment in the T-maze.
      However, no significant impairments were observed in the T-maze at 3 months or
      the water maze at 3 or 12 months postdosing. At 24 months, TET-treated rats
      showed significant deficits in acquisition and retention of the water maze task
      compared with age-matched controls. Both groups of 24 months old rats were
      significantly impaired compared with young controls. At 24 months, there was a
      general age-related decrease in the optical density of Timm's staining in
      cortical regions (9%), compounded by a further decrease in the entorhinal cortex
      and outer molecular layer of the dentate gyrus of the hippocampus in TET treated
      rats (30%). These data indicate that early developmental exposure to an
      organometal resulted in morphological damage that was apparent behaviorally only
      during early postnatal development and with advanced aging.

PMID- 8532106
TI  - Amyloid beta protein (A beta) removal by neuroglial cells in culture.
AB  - Because the mechanisms of A beta degradation in normal and Alzheimer's disease
      brain are poorly understood, we have examined whether various cortical cells are
      capable of processing this peptide. Rat microglia and astrocytes, as well as the
      human THP-1 monocyte cell line, degraded A beta 1-42 added to culture medium. In
      contrast, neither rat cortical neurons or meningeal fibroblasts effectively
      catabolized this peptide. When A beta fibrils were immobilized as plaque-like
      deposits on culture dishes, both microglia and THP-1 cells removed the peptide.
      Astrocytes were incapable of processing the A beta deposits, but these cells
      released glycosaminoglycase-sensitive molecules that inhibited the subsequent
      removal of A beta by microglia. This implied that astrocyte-derived proteoglycans
      associated with the amyloid peptide and slowed its degradation. The addition of
      purified proteoglycan to A beta that was in medium or focally deposited also
      resulted in significant inhibition of peptide removal by microglia. These data
      suggest that A beta can be catabolized by microglia and proteoglycans which co
      localize with senile plaques may slow the degradation of A beta within these
      pathologic bodies.

PMID- 8532107
TI  - Serum alpha 1-antichymotrypsin level as a marker for Alzheimer-type dementia.
AB  - Excessive alpha 1-antichymotrypsin (ACT) in brain has been postulated to play a
      role in the pathogenesis of Alzheimer's disease (AD). We measured serum ACT by
      radial immunodiffusion in 57 patients with presumed AD, 110 healthy controls (24
      children; 86 adults), 67 non-AD patients from a geriatric private practice and a
      VA nursing home, and 136 asthmatics (56 adults; 80 children) as an inflammatory
      disease control group. Serum ACT was significantly higher in AD (73.1 +/- 22
      mg/dl) than in healthy controls (47.9 +/- 8.1 mg/dl) or non-AD patients (61.8 +/-
      23.9 mg/dl). A level of 60 mg/dl best separated AD patients from controls or non
      AD patients. Serial measurements served to distinguish elevations of ACT level in
      AD from non-AD inflammatory conditions; the ACT level in the latter returned to
      normal with therapy or time, but the levels in AD remained elevated. A measure of
      serum ACT by radial immunodiffusion can be used to support a diagnosis of AD
      disease but not necessarily as a screening test due to the potentially large
      number of false positives (26% in the population studied) should malignancy or
      inflammatory disease be concurrent.

PMID- 8532108
TI  - Soluble multimeric Alzheimer beta(1-40) pre-amyloid complexes in dilute solution.
AB  - Aqueous solutions of beta(1-40) peptide spontaneously associate to form
      pentameric/hexameric complexes that can be demonstrated by SDS-PAGE following
      treatment with glutaraldehyde and borohydride reduction. Under amyloidogenic
      conditions of pH and high peptide concentration these aggregates can further
      associate to form pentameric/hexameric complexes that can be demonstrated by SDS
      PAGE following treatment with glutaraldehyde and borohydride reduction. Under
      amyloidogenic conditions of pH and high peptide concentration these aggregates
      can further associate to form sedimentable and filterable structures with beta
      sheet amyloid characteristics of Thioflavine T fluorescence. The presence of such
      preamyloid structures at low peptide concentration suggests a mechanism by which
      amyloid plaques can accrete additional material by a cooperative rather than
      monomeric growth. The existence of a monomer<==>multimer equilibrium may partly
      explain the divergence of biological consequences with respect to neurotoxicity.

PMID- 8532109
TI  - Circadian locomotor activity and core-body temperature rhythms in Alzheimer's
      disease.
AB  - Sleep-wake cycle disturbances suggest that circadian rhythms may be disrupted in
      patients with Alzheimer's disease (AD). In this study, we examined the circadian
      rhythms of core-body temperature and locomotor activity in 28 patients with
      probable AD and 10 healthy controls. AD patients had higher percent nocturnal
      activity than controls, corresponding to the clinical picture of fragmented
      sleep. The amplitude of the activity cycle in the AD patients was lower than that
      of controls and the acrophase of this cycle in AD patients was 4.5 h later. There
      was no difference in the amplitude of the core-body temperature circadian rhythm,
      but AD patients had delayed temperature acrophases. A subgroup of AD patients
      with large mean time differences between the acrophases of their activity and
      temperature cycles had lower temperature amplitudes and greater activity during
      the night. These findings suggest that a subgroup of AD patients with impaired
      endogenous pacemaker function may have a diminished capacity to synchronize the
      rhythm of core-body temperature with the circadian cycle of rest-activity. This
      circadian rhythm dysfunction may partly explain the fragmented nocturnal sleep
      exhibited by these patients.

PMID- 8532110
TI  - Rat tail artery norepinephrine release: age and effect of mitochondrial blockade.
AB  - An age-related increase in stimulation-evoked fractional norepinephrine release
      has been demonstrated in tail artery of Fischer-344 rats from 6 to 20 months of
      age. Previous studies have ruled out alterations in function of uptake
      mechanisms, metabolism, or feedback via prejunctional alpha-2 adrenoceptors,
      suggesting that an age-related decline in calcium homeostasis may be responsible.
      To test this possibility, stimulation-evoked fractional norepinephrine release
      from perivascular adrenergic nerves of rat tail arteries in the presence of a
      blocker of mitochondrial calcium uptake, dinitrophenol (100 microM), was measured
      using HPLC with electrochemical detection. When the mitochondrial proton gradient
      was dissipated by dinitrophenol, tail arteries from 20-month-old animals showed a
      marked increase in stimulation-evoked norepinephrine release whereas arteries
      from 6-month-old animals were not affected. One hypothesis is that the inhibition
      of mitochondrial calcium uptake in the adrenergic nerves from older animals
      resulted in an elevated intracellular calcium level. In agreement with this idea,
      when extracellular calcium was raised from 1.6 to 5 mM, stimulation-evoked
      norepinephrine release was increased in the 6-month tail arteries in the presence
      of dinitrophenol. These data suggest that there may be a decline in calcium
      regulation in older nerves leading to increased norepinephrine release with
      advancing age.

PMID- 8532111
TI  - Beta amyloid is neurotoxic in hippocampal slice cultures.
AB  - We examined the neurotoxicity of the 40 amino acid fragment of beta amyloid
      peptide (A beta 1-40) in cultured hippocampal slices. When injected into area
      CA3, A beta 1-40 produced widespread neuronal damage. Injection of the reverse
      sequence peptide, A beta 40-1, or vehicle alone produced little damage. The
      distribution A beta 1-40 was highly correlated with the area of neuronal damage.
      Thioflavine S and electron microscopic analysis confirmed that injected A beta 1
      40 formed 7-9 nm AD type amyloid fibrils in the cultures. A beta 1-40 also
      altered the number of GFAP immunoreactive astrocytes and ED-1 immunoreactive
      microglia/macrophages within and around the A beta 1-40 deposit. The observed
      neurotoxicity of A beta 1-40 in hippocampal slice cultures provides evidence that
      this peptide may be responsible for the neurodegeneration observed in AD.

PMID- 8532112
TI  - Nimodipine facilitates retention of the classically conditioned nictitating
      membrane response in aged rabbits over long retention intervals.
AB  - Aged rabbits initially underwent 18 days of acquisition of the classically
      conditioned nictitating membrane response (NMR) using a tone conditioned stimulus
      (CS) and an air puff unconditioned stimulus (UCS). They were then treated with a
      low or high dose of nimodipine or a vehicle for 90 days. During this time no
      further CS-UCS pairings were presented. They underwent testing for retention of
      the conditioned response (CR) at 30 and 90 days. Retention testing consisted of
      20 presentations of the CS alone. Rabbits in the control condition retained 46.4%
      of their predrug levels of conditioned responding and rabbits receiving the low
      dose of nimodipine retained 37.3% of their predrug levels after 30 days. After 90
      days, retention in these animals declined to 8.1% and 14.1%, respectively. In
      contrast, rabbits receiving the high dose of nimodipine retained 85% of their
      predrug learning at 30 days with little decline at 90 days (77.1%).
      Nonassociative factors such as sensitivity to the CS or UCS could not explain
      these effects.

PMID- 8532113
TI  - Role of microglia in senile plaque formation.
AB  - To assess the role of microglial cells in senile plaque (SP) formation, we
      examined the density and distribution of microglia in the temporal neocortex of
      three groups of nondemented individuals, chosen to represent sequential stages of
      SP formation (no SP, n = 14; diffuse plaques (DP) only, n = 12; both DP and
      neuritic plaques (NP), n = 14) and patients with Alzheimer's disease (AD, n =
      11). The mean density of microglia was significantly greater in the AD group. In
      nondemented individuals, the presence of NP but not DP was associated with an
      increased number of microglial cells. Most NP (91%) were focally associated with
      microglial cells. DP less commonly contained microglia, however, individuals with
      some NP had microglia within a greater proportion of their DP (47%) than did
      those with only DP (19%). These findings suggest that: (a) microglia are not
      involved in the formation of DP; (b) the presence of NP is associated with both
      an overall increase in microglia and the focal aggregation of cells around NP;
      (c) microglia may be locally involved in the conversion of DP into NP. This final
      point represents the most significant aspect of this study, providing the first
      quantitative evidence to support a specific role for microglia in the formation
      of NP from DP.

PMID- 8532114
TI  - beta-Amyloid precursor protein gene in squirrel monkeys with cerebral amyloid
      angiopathy.
AB  - Senescent nonhuman primates frequently develop cerebral beta-amyloidosis; for
      reasons that are not yet understood, the primary histological locus of beta
      amyloid deposition varies in different species. In aged rhesus monkeys (Macaca
      mulatta), fibrillar (congophilic) beta-amyloid (A beta) occurs most frequently in
      senile plaques, whereas in aged squirrel monkeys (Saimiri sciureus) the cerebral
      blood vessels are most affected. To determine if cerebral beta-amyloid angiopathy
      (CAA) in squirrel monkeys is related to a species-specific amino acid change in A
      beta, as was shown in two hereditary human forms of CAA, the beta-amyloid
      precursor protein (beta PP) cDNA was sequenced. The predicted amino acid sequence
      of A beta in squirrel monkeys is identical to that in normal humans. Overall,
      beta PP751 in the squirrel monkey differs from the human sequence only by four
      amino acids near the N-terminus and in the KPI domain. These findings suggest
      that other factors most likely predispose aged squirrel monkeys to cerebral
      amyloid angiopathy. We propose the squirrel monkey as a useful model for studying
      the factors contributing to human CAA, and for testing diagnostic and therapeutic
      approaches to this disorder.

PMID- 8532115
TI  - Altered cell calcium regulation in synaptosomes and brain cells of the 30-month
      old rat: prominent effects in hippocampus.
AB  - A deficient regulation of neuronal cytosolic calcium levels has been suggested to
      play a role in the pathogenesis of neurodegeneration. However, evidence for an
      alteration in cytosolic calcium regulation in old age is at present
      controversial. The present work was aimed at studying whether changes in
      synaptosomal calcium homeostasis in 30-month-old rats are uniform throughout the
      brain or affect specific brain regions. A second question addressed in this work
      is whether the effect of ageing on calcium homeostasis is restricted to the nerve
      terminal or a more general process affecting also cell bodies. To study these
      questions cytosolic calcium regulation was studied in parallel in synaptosomes
      and a preparation of acutely dissociated brain cells obtained from different
      regions of 3- and 30-month-old rats. 45Ca2+ accumulation and distribution in
      mitochondria (assessed as FCCP-releasable 45Ca2+) was also studied. Mean [Ca2+]i
      obtained at rest and after high K+ depolarization were unchanged in cerebral
      cortex synaptosomes but increased in hippocampal synaptosomes at 30 months.
      Resting [Ca2+]i also increased with age in hippocampal, but not cerebral cortex
      cells, whereas the increase in [Ca2+]i obtained by depolarization was larger in
      both brain regions. Calcium compartmentation in mitochondria from hippocampal
      neurons incubated under high K+ conditions was also decreased with ageing. An
      altered calcium regulation in cell bodies and synaptic terminals in the
      hippocampus may be involved in the development of functional impairments in the
      hippocampal formation.

PMID- 8532116
TI  - Differential correlation between neurochemical deficits, neuropathology, and
      cognitive status in Alzheimer's disease.
AB  - The relationships between neurofibrillary tangles (NFT), senile plaques (SP), and
      the deficits in somatostatin (SRIH) and choline acetyltransferase (ChAT) levels
      were determined in Brodmann area 9, 40, 22, and 17/18 in 12 women whose Blessed
      test score (BTS) ranged from 27 to 1. NFT density correlated with the cognitive
      decline in areas 9, 40, and 22 and with SP number in area 22 and 17/18. ChAT
      levels were linked to the BTS in area 9, 40, and 22 and SRIH levels in area 9
      only. ChAT, but not SRIH, did correlate with SP (area 22) and NFT (area 40 and
      22). Decreases in ChAT and SRIH were correlated in areas 9 and 22. These results
      indicate that the somatostatinergic deficit in Alzheimer's disease is more
      regionally restricted than the cholinergic one. The correlation between SRIH and
      ChAT as observed in area 9 and 22 may indicate that somatostatin- and
      acetylcholine-containing elements in the frontal and temporal lobes are
      particularly relevant to the cognitive decline as observed in Alzheimer's
      disease.

PMID- 8532117
TI  - PET studies of cerebral glucose metabolism in conscious rhesus macaques.
AB  - A growing body of evidence suggests that rhesus macaques may be a good model of
      human brain aging. We used positron emission tomography (PET) and 18F
      fluorodeoxyglucose (FDG) to measure regional cerebral metabolic rates for glucose
      (rCMRglc) in young and aged rhesus macaques to determine if age-related
      decreases, such as those reported in humans, also occur in macaques. Whereas the
      aged animals had lower metabolic rates in every brain region studied, the largest
      differences were in left temporal cortex. The largest differences were also
      observed in left temporal cortex when relative rCMRglc values were used. Both
      rCMRglc and relative rCMRglc were marked by substantial individual variation
      within the aged group. This variation may parallel the variation observed in
      behavioral studies. Future studies that include both PET and behavioral measures
      should help determine if there is a relationship between age-related changes in
      rCMRglc and behavior.

PMID- 8532118
TI  - Monoamine oxidase isoenzymes in rat brain: differential changes during postnatal
      development but not aging.
AB  - Differential development of monoamine oxidase (MAO) isoenzymes in rat whole brain
      is described in postnatally developing Sprague-Dawley rats. Total MAO and
      isoenzyme activity was measured using nonspecific and specific substrates. Total
      MAO activity measured using tyramine, increased postnatally up to 24 weeks of age
      and attained a plateau afterward. The increase in total MAO activity was
      significant at all age groups (18 days to 36 months) investigated as compared to
      new born rats. MAO-A and MAO-B activities were measured using octopamine and
      benzylamine respectively. We also observed a marginal increase of MAO-A activity
      and a significant increase of MAO-B activity upon development. Furthermore, at 12
      weeks of age, MAO-B activity increased by 10-fold as compared to new born and was
      consistent up to 36 months of age. The qualitative localization of the enzyme
      activity on non SDS-PAGE by nitroblue tetrazolium staining confirmed the increase
      of MAO-B during the development. It is suggested that the maturational increase
      of total MAO activity in brain is predominantly due to the increase of MAO-B
      isoenzyme.

PMID- 8532119
TI  - Neuroendocrine involvement in aging: evidence from studies of reproductive aging
      and caloric restriction.
AB  - Neuroendocrine changes contribute to female reproductive aging, but changes in
      other tissues also play a role. In C57BL/6J mice, neuroendocrine changes
      contribute to estrous cycle lengthening and reduced plasma estradiol levels, but
      the midlife loss of cyclicity is mainly due to ovarian failure. Hypothalamic
      estrogen receptor dynamics and estrogenic modulation of gene expression are
      altered in middle-aged cycling mice. Although insufficient to arrest cyclicity,
      these neuroendocrine changes may contribute to other reproductive aging
      phenomena, such as altered gonadotropin secretion and lengthened estrous cycles.
      In women, the loss of ovarian oocytes, the cause of menopause, accelerates in the
      decade before menopause. Accelerated oocyte loss may in turn be caused by a
      selective elevation of plasma follicle stimulating hormone, and neuroendocrine
      involvement may thus be implicated in menopausal oocyte loss. Chronic calorie
      restriction retards both neural and ovarian reproductive aging processes, as well
      as age-related change in many other physiological systems. The diverse effects of
      food restriction raises the possibility of an underlying coordinated regulatory
      response of the organism to reduced caloric intake, possibly effected through
      alterations of neural and/or endocrine signalling. We are therefore attempting to
      identify neuroendocrine changes that may coordinate the life prolonging response
      of animals to food restriction. Our initial focus is on the glucocorticoid
      system. Food restricted rats exhibit daily periods of hyperadrenocorticism,
      manifest as elevated free corticosterone during the diurnal peak. We hypothesize
      that this hyperadrenocortical state potentiates cellular and organismic
      homeostasis throughout life in a manner similar to that achieved during acute
      stress, thereby retarding aging processes and extending life span.

PMID- 8532120
TI  - Use of caloric restriction to investigate neuroendocrine involvement in aging.

PMID- 8532121
TI  - Do the salutary effects of food restriction occur because of or despite of the
      accompanying hyperadrenocorticism?

PMID- 8532122
TI  - Aging and caloric restriction: human effects and mode of action.

PMID- 8532123
TI  - Neuroendocrine involvement in the aging: evidence from studies of reproductive
      aging and caloric restriction.

PMID- 8532124
TI  - Nicotine enhances Morris water maze performance of young and aged rats.
AB  - We have recently demonstrated that nicotine administration improves the
      acquisition and/or memory retention of aged rats in 17-arm radial maze, Lashley
      III maze, and one-way active avoidance testing. The present study extends our
      evaluation of nicotine's cognition-enhancing potential by determining the effect
      of nicotine on acquisition and retention of the Morris water maze in young adult
      (2 to 3 months old) and aged (25 to 26 months old) Sprague-Dawley rats. For 3
      days prior to the onset of testing, and 15 min prior to daily testing, rats were
      treated IP with 0.2 mg/kg nicotine or saline vehicle. Compared to the performance
      of young adults, vehicle-treated aged rats were impaired in water maze
      acquisition. Nicotine substantially enhanced the acquisition of aged rats.
      Furthermore, nicotine significantly improved the memory retention of young adult
      rats. These cognitive improvements may involve a nicotine-receptor induced
      increase in generalized alertness and/or a facilitation of higher integrative
      function. The results suggest that nicotine and/or nicotinic agonists may be
      useful in treating age-associated memory impairment and/or Alzheimer's disease.

PMID- 8532125
TI  - Growth inhibition of human glioma cells by superinduced human interferon-beta.
AB  - Superinduction of human interferon-beta (HuIFN-beta) from human glioma cells has
      greater cytotoxicity than purified HuIFN-beta derived from fibroblasts. However,
      superinduction requires several reagents like polyI:polyC, cycloheximide, and
      actinomycin D, which may contaminate the conditioned medium and obscure the
      effect of superinduced HuIFN-beta. The present study used minimum doses of
      polyI:polyC and cycloheximide without actinomycin D to superinduce HuIFN-beta.
      The superinduced HuIFN-beta was purified by passing the medium through molecular
      sieve column chromatography. Fractionation of the eluate provided semipurified
      superinduced HuIFN-beta which demonstrated a growth inhibitory effect against
      both the U251-MG autologous human glioma cell line and the SK-MG-1 homologous
      glioma cell line. This effect was neutralized by addition of anti-HuIFN-beta
      monoclonal antibody (YSB-1). In a separate experiment, combinations of
      superinduction reagents were found not to have growth inhibitory effects because
      all inhibition in superinduced medium was completely neutralized by YSB-1.
      Superinduced HuIFN-beta has a pure growth inhibitory effect on both autologous
      and homologous glioma cells, so may affect autocrine secretion of cytokines.

PMID- 8532126
TI  - Antiproliferative effect of multiple autocrine loop blockade in human malignant
      glioma cell lines.
AB  - The effects of specific antibodies against growth factors and receptors on
      deoxyribonucleic acid (DNA) synthesis in two established human glioma cell lines,
      A172 and TM-1, were examined. Anti-platelet-derived growth factor (PDGF), anti
      basic fibroblast growth factor (bFGF), and anti-epidermal growth factor receptor
      (EGF-R) antibodies inhibited thymidine incorporation by both cell lines in serum
      free medium. Antibody specific to transforming growth factor-alpha only slightly
      suppressed DNA synthesis by both cell lines. Although the antiproliferative
      effects of anti-PDGF and anti-bFGF antibodies decreased in serum-supplemented
      medium, the effect of anti-EGF-R antibody was little changed. The combination of
      anti-PDGF, anti-bFGF, and anti-EGF-R antibodies significantly inhibited thymidine
      incorporation by the two cell lines even in serum-supplemented medium. This
      preliminary study suggests that simultaneous blockade of multiple autocrine loops
      may provide a new approach to the treatment of human malignant gliomas.

PMID- 8532127
TI  - Production of tissue inhibitor of metalloproteinases-1 (TIMP-1) by human
      astrocytic tumors.
AB  - Production of tissue inhibitor of metalloproteinases-1 (TIMP-1), a specific
      inhibitor of matrix metalloproteinases, was investigated in human astrocytic
      tumors (n = 15) and normal brain tissues (n = 3). Enzyme immunoassay indicated
      that TIMP-1 levels in the culture media of tumor explants were significantly
      higher in glioblastomas as compared with anaplastic astrocytomas, astrocytomas,
      and normal brain tissues. Immunohistochemistry using a monoclonal antibody
      against TIMP-1 demonstrated that TIMP-1 was detectable mainly in tumor cells,
      especially in glioblastoma. These results suggest that increased expression of
      TIMP-1 is associated with the malignant progression of astrocytic tumors.

PMID- 8532128
TI  - Combined cisternal drainage and intrathecal urokinase injection therapy for
      prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage.
AB  - The effect of cisternal drainage and intrathecal urokinase injection in
      preventing symptomatic vasospasm (SVS) after aneurysmal subarachnoid hemorrhage
      was studied in 60 patients with uniform background (Hunt & Kosnik grade III,
      younger than 70 yrs, undergoing surgery within 72 hrs after hemorrhage). The
      incidence of permanent neurological deficits caused by vasospasm was 5/16 without
      cisternal drainage, 5/34 with drainage alone, and 1/10 with drainage and
      urokinase injection. Analysis of patients without postoperative cisternal
      drainage showed the amount of subarachnoid clot on the initial computed
      tomographic scan was closely related to the occurrence of SVS (p < 0.05, unpaired
      t test). Analysis of patients with cisternal drainage showed the amount of bloody
      cerebrospinal fluid (CSF) drained during the 10 days after surgery and the
      duration of drainage placement were critical in preventing vasospasm (p < 0.05,
      unpaired t test). Greater CSF drainage significantly reduced the incidence of
      permanent neurological deficits caused by vasospasm (p < 0.01, chi 2), but
      significantly increased the incidence of hydrocephalus requiring shunt procedures
      (p < 0.01, chi 2). Urokinase injection via cisternal drainage achieved a further
      reduction in the occurrence of SVS. Intrathecal thrombolytic therapy after
      aneurysmal surgery is an effective method for SVS prophylaxis, and CSF drainage
      (> 1500 ml for 10 days) enhances the effect.

PMID- 8532129
TI  - Gamma knife radiosurgery for acoustic schwannoma: early effects and preservation
      of hearing.
AB  - The effects of relatively low dose gamma knife irradiation on acoustic schwannoma
      were evaluated. The signal intensity change and tumor shrinkage on magnetic
      resonance (MR) images, change in hearing, and complications in 28 patients (mean
      age 47.0 +/- 13.6 yrs) were studied. Three patients had bilateral tumors. Six
      were already deaf when treated. The maximum tumor diameter was 35 mm. The mean
      dose delivered to the tumor was 12.1 +/- 1.6 Gy at the periphery, and 25.2 +/-
      4.3 Gy at the center. The mean follow-up time was 16 months and the longest 24
      months. Lowering of the MR signal intensity in the tumor center appeared after 3
      months at earliest but generally after 6 months. Signs of tumor shrinkage
      appeared within 12 months on average. Cyst in the tumor enlarged rapidly after
      treatment in two patients. The percentage of hearing preservation was 85% (17/20)
      at 3 months, 80% (16/20) at 6 months, 72% (13/18) at 9 months, 75% (12/16) at 12
      months, 67% (8/12) at 15 months, 60% (6/10) at 18 months, and 50% (2/4) at 24
      months. Subtle changes in hearing were detected by speech tone audiometry.
      Temporary facial numbness and weakness was seen in one patient each. No patient
      had lower cranial nerve paresis. Relatively low dose gamma knife radiosurgery is
      effective in suppressing growth of acoustic schwannoma with preservation of
      hearing.

PMID- 8532130
TI  - Choroid plexus carcinoma in the lateral ventricle--case report.
AB  - A 68-year-old male presented with choroid plexus carcinoma in the left lateral
      ventricle manifesting as dysarthria and gait disturbance. Magnetic resonance
      imaging showed a homogeneously enhanced mass in the trigone of the left lateral
      ventricle. Selective left posterior cerebral arteriography showed the tumor was
      fed by the left medial posterior choroidal artery. Detailed examinations found no
      evidence of an extraneural primary focus. He underwent partial removal of the
      tumor followed by local Lineac irradiation (50 Gy). After irradiation, the serum
      level of carcinoembryonic antigen decreased and the size of the residual tumor
      was reduced.

PMID- 8532131
TI  - Endovascular treatment of an extracranial internal carotid artery aneurysm at the
      skull base with mechanically detachable coils--case report.
AB  - A 45-year-old male experienced a transient ischemic attack manifesting as left
      blurred vision and right hemiparesis. Angiography demonstrated an extracranial
      internal carotid artery aneurysm at the entrance of the carotid canal just above
      the C-1 vertebral arch. Intraluminal occlusion of the aneurysm was achieved with
      mechanically detachable coils under local anesthesia, and the carotid flow was
      preserved. There was no complication during or following the procedure. Treatment
      of aneurysms using detachable coils is an important alternative to surgical
      treatment when surgical access to the lesion is difficult.

PMID- 8532132
TI  - Epidural hematoma associated with cephalohematoma in a neonate--case report.
AB  - A female neonate presented with cephalohematoma over the temporoparietal region
      on the right side. Computed tomography (CT) revealed the presence of an
      underlying epidural hematoma (EDH) and associated skull fracture with
      communication between the hematomas. Aspiration of the cephalohematoma was
      followed by reduction in the size of the EDH. CT revealed cure without the need
      for an operative procedure. Aspiration is indicated for neonatal EDH with mild
      symptoms and liquefied cephalohematoma.

PMID- 8532133
TI  - Instrumentational posterior fusion for atlanto-axial subluxation in a young child
      with Down's syndrome--case report.
AB  - A 3-year-old girl with Down's syndrome and myelopathy caused by atlanto-axial
      subluxation (AAS) was treated by C-1 to C-2 posterior fusion with a one-piece
      cervical device (OPCD). Instrumentation was required because the posterior arch
      of C-1 was too tiny and fragile to tolerate wiring. Postoperative immobilization
      was another major problem in this mentally retarded young child, but a hard
      plastic cervical corset effectively restrained the neck. She had been confined to
      bed by severe quadriparesis, but became able to walk without assistance 8 months
      after surgery. We recommend OPCD instrumentation and postoperative immobilization
      using a hard plastic corset for the treatment of AAS associated with Down's
      syndrome in young children.

PMID- 8532134
TI  - Endovascular treatment with an ultra-thin 4-French guiding catheter via the
      transfemoral and transbrachial routes--technical note.
AB  - An ultra-thin-walled 4-French catheter was used for angiography and as a guiding
      catheter for the Tracker-18 microcatheter in patients with intracranial dural
      arteriovenous fistulas (AVFs), spinal dural AVFs, spinal epidural AVF,
      meningioma, and acute embolic occlusion of major cerebral vessels. The 4-French
      guiding catheter was introduced through the transfemoral or transbrachial route.
      The guiding catheter and the guidewire were advanced to the aortic arch and then
      turned over just above the aortic valves, and finally the catheter was introduced
      into the external carotid artery or vertebral artery when the transbrachial
      approach was selected. Images of the intracranial vessels and spinal dural
      branches obtained were excellent in all cases. The Tracker-18 could smoothly be
      advanced to the target artery through the 4-French catheter in all patients.
      Endovascular treatment with the Tracker-18 can be performed using an ultra-thin 4
      French guiding catheter, and safely via the transbrachial route.

PMID- 8532135
TI  - Adenosine receptors.

PMID- 8532136
TI  - Acetylcholine contractures of skeletal muscles: inhibition by chlorpromazine and
      diltiazem.
AB  - The maximum contractures evoked by 100 microM ACh of mouse soleus muscles
      denervated for 3-7 days are completely inhibited by a 10 min exposure to 100
      microM chlorpromazine (CP). Recovery on washout of CP takes more than 1 hr to
      complete. ACh evoked contractures are also inhibited by diltiazem (D); washout of
      D is immediately followed by recovery. Electrically evoked twitches and K evoked
      contractures are largely unaffected by CP, caffeine evoked contractures are
      decreased but not abolished. Fast mouse and (non-denervated) frog tonic muscles
      behave similarly. Depolarization by ACh and ACh-evoked whole cell currents show
      enhanced desensitization at low, and block at high [CP] and [D]; more than 50%
      recovery is achieved by less than 1 min washout of CP and D. Currents carried by
      Na+ and Mg2+ ions behave similarly. It is concluded that activation of ACh evoked
      contractures may be blocked by CP independent of ionic currents through nicotinic
      ACh receptors and that it depends on intracellular processes linked to these
      receptors.

PMID- 8532137
TI  - On the probabilistic nature of excitotoxic neuronal death in hippocampal neurons.
AB  - In an attempt to distinguish hypothesized rapid and slow components, we have
      systematically studied the time course of hippocampal neuronal death in an in
      vitro model of excitotoxicity. In all paradigms involving glutamate, NMDA or AMPA
      as toxins, the population of trypan-blue excluding (live) neurons progressively
      declined over 48 hr. The percent survival over time could be fit mathematically
      using single exponential decay curves, implying that the death of any individual
      neuron was a stochastic event. One or two hours after glutamate exposure,
      prevention of further glutamate-receptor interactions by addition of MK-801 or MK
      801 plus CNQX resulted in the survival of 60-80% of the original population at 24
      hr. Thus delayed, continuous blockade of secondary glutamate receptor stimulation
      was protective, apparently interrupting the cyclic nature of the toxicity
      cascade. Twelve hours of MK-801 immediately following glutamate removal protected
      the majority of cells during the period of active receptor blockade. As soon as
      MK-801 was removed, the progressive decay in population size resumed, indicating
      that short term receptor blockade was insufficient to prevent expression of the
      initial injury. A kinetic model is proposed to place these experimental results
      into a framework for discussion and formulation of future experimentation.

PMID- 8532138
TI  - Therapeutic brain concentration of the NMDA receptor antagonist amantadine.
AB  - Amantadine (1-amino-adamantane) is clinically used for the management of
      Parkinson's disease and drug-induced extrapyramidal symptoms. It has previously
      been shown that amantadine is a low-affinity uncompetitive N-methyl-D-aspartate
      (NMDA) receptor antagonist with rapid blocking and unblocking channel kinetics
      (Ki-value at the PCP binding site = 10 microM). The aim of the present studies
      was to estimate concentrations of amantadine in the central nervous system under
      therapeutic conditions. In homogenates of postmortem human brain tissue the
      amantadine concentration appeared to be homogeneously distributed over a wide
      range of brain areas. Amantadine concentration increased with duration of
      treatment and decreased wit drug-free time. When the duration of treatment was >
      or = 10 days and drug-free time < or = 3 days, mean amantadine concentrations in
      postmortem brain tissue ranged from 48.2 to 386 microM. In contrast to brain
      tissue, amantadine concentration in cerebrospinal fluid (CSF) and serum was in
      the low micromolar range ( < 17 microM). CSF and serum total values were highly
      correlated to each other and were always lower in CSF. The mean CSF/serum ratio
      for total amantadine was 0.76. To further estimate the extracellular
      concentration, amantadine was determined in microdialysates in the rat striatum.
      At behaviorally active doses, amantadine concentration in striatal
      microdialysates ranged between 6 and 21 microM. These results indicate that
      extracellular concentrations of amantadine (CSF and serum values in patients,
      striatal microdialysates in the rat) are in the range of its Ki-value at the PCP
      binding site. Amantadine concentrations in brain tissue are much higher, probably
      due to intralysosomal accumulation.

PMID- 8532139
TI  - Mechanism for nitric oxide's enhancement of NMDA-stimulated [3H]norepinephrine
      release from rat hippocampal slices.
AB  - Previous studies in our laboratory have shown that nitric oxide (NO) gas enhances
      NMDA-stimulated release of preloaded tritiated norepinephrine ([3H]NA) from rat
      brain slices in a dose-dependent, oxygen-sensitive, and cyclic GMP-independent
      manner. In this study we have attempted to determine the mechanism for the
      enhancement of neurotransmitter release seen with NO. No-enhanced transmitter
      release was not due to buffer acidification or generation of NO degradation
      products, since reducing buffer pH below 7.3 inhibited NMDA-stimulated [3H]NA
      release and nitrite or nitrate ions (3-100 microM) had no significant effect on
      release. Carbon monoxide (CO, 10-300 microM), another diatomic gas with
      properties similar to NO including heme binding and guanylate cyclase activation,
      had no significant effect on depolarization-induced [3H]NA release. The NO effect
      was probably not due to mono-ADP-ribosylation of cellular proteins, since the ADP
      ribosyltransferase (ADPRT) inhibitors nicotinamide (10 microM-10 microM) and
      luminol (1 microM-1mM) did not diminish the enhancement of transmitter release
      seen with NO. The NA reuptake inhibitor desmethylimipramine (DMI, 10 nM-10
      microM) neither mimicked nor blocked the effect of NO, suggesting that NO was not
      acting via inhibition or reversal of the NA transporter. Similar to NO, the
      metabolic inhibitors sodium azide (NaN3, 0.1-3 mM), potassium cyanide (KCN, 0.1-3
      mM), and 2,4-dinitrophenol (2,4-DNP, 10-300 microM) also dose-dependently
      enhanced NMDA-stimulated [3H]NA release. These results suggest that NO may
      enhance neurotransmitter release by inhibiting cellular respiration and perhaps
      ultimately via altering calcium homeostasis.

PMID- 8532140
TI  - Ca/calmodulin-dependent kinase II inhibitor KN62 attenuates glutamate release by
      inhibiting voltage-dependent Ca(2+)-channels.
AB  - The effect of KN62 (1-[N,O-bis(5-isoquinolinesulphonyl)-N -methyl-L-tyrosyl]-4
      phenylpiperazine), a putative inhibitor of Ca/calmodulin-dependent kinase II
      (Ca/CaM-K II), on glutamate release from isolated nerve-terminals (synaptosomes)
      was examined. The drug caused a potent inhibition of KCl- and 4-aminopyridine
      evoked glutamate release from isolated nerve-terminals (synaptosomes).
      Examination of the effect of the inhibitor on Ca(2+)-influx revealed that the
      diminution of glutamate release could be attributed to a decrease in cytosolic
      Ca. A direct effect of KN62 on synaptosomal Ca(2+)-channels was confirmed in
      experiments where Ba, which does not support CaM-dependent processes, was used in
      place of Ca. Additionally, whole-cell patch-clamping of cerebellar granule
      neurones directly demonstrated inhibition of Ca-currents by KN62. We therefore
      suggest that, in cellular systems, conclusions based on the use of KN62 as a
      Ca/CaM-K II blocker may be ambiguous and should be viewed with caution unless the
      effect of the drug on Ca-influx has also been quantified. The effect of KN62 on
      Ca(2+)-influx appears to be specific to slowly-or non-inactivating conductances,
      and therefore presents KN62 as a potentially useful tool in this context.

PMID- 8532141
TI  - Affinity purification of rat cortical and chicken forebrain synaptosomes using a
      biotinylated derivative of omega-CgTx GVIA.
AB  - We describe a magnetophoretic method for the affinity purification of
      synaptosomes expressing omega-CgTx GVIA-sensitive, N-type voltage-sensitive
      calcium channels (VSCCs). The method utilizes a biotinylated derivative of omega
      CgTx GVIA which retains its ability to displace [125I] omega-CgTx GVIA from its
      binding sites on rat synaptic membranes. When coupled to streptavidin coated
      magnetizable beads, the hexanoyl spacer between omega-CgTx GVIA and the
      biotin:streptavidin bead complex is sufficiently long to allow flexibility of the
      toxin to bind to its receptor on synaptosomes. We have used this ligand
      successfully to isolate deaggregated synaptosomes from the parent fractions of
      chicken forebrain and rat cortex. In the chicken synaptosome parent fraction,
      omega-CgTx GVIA (1 nM-1 microM) produced a concentration-dependent block of the
      KCl-induced intracellular free Ca2+, [Ca2+]i, elevation with an IC50 of 28 nM.
      After affinity magnetophoresis no increase in [Ca2+]i elevation was observed in
      either the bound or unbound fractions. In the rat synaptosome parent fraction,
      the KCl-induced increase in free intracellular Ca2+ ([Ca2+]i) elevation was
      partially blocked by omega-CgTx GVIA (17 +/- 2% / 1 microM) and to a greater
      extent by omega-Aga IVA (55 +/- / 1 microM): a combination of the two toxins was
      additive (72 +/- 4% / 1 microM). The block obtained by omega-CgTx GVIA (1 microM)
      in the unbound fraction was reduced to 3 +/- 2%, whereas that by omega-Aga IVA (1
      microM) increased to 82 +/- 3%. The block obtained by a combination of both
      toxins (83 +/- 2%) was the same as that with omega-Aga IVA alone (82 +/- 3%). No
      increase in free [Ca2+]i elevation was observed in the bound fraction although
      single synaptosome-like structures, displaying synaptophysin immunoreactivity,
      were detected on the beads. We conclude that omega-CgTx GVIA-sensitive N-type
      calcium channels are present on all chicken forebrain synaptosomes but only a
      subset of rat cortical synaptosomes.

PMID- 8532142
TI  - Characteristics of a human N-type calcium channel expressed in HEK293 cells.
AB  - The human alpha 1B-1 alpha 2b beta 1-2 Ca2+ channel was stably expressed in
      HEK293 cells producing a human brain N-type voltage-dependent calcium channel
      (VDCC). Whole cell voltage-clamp electrophysiology and fura-2 based
      microfluorimetry have been used to study its characteristics. Calcium currents
      (ICa) recorded in transfected HEK293 cells were activated at potentials more
      depolarized than -20 mV with peak currents occurring at approx + 10 mV in 5 mM
      extracellular CaCl2. ICa and associated rises in intracellular free calcium
      concentrations ([Ca2+]i) were sensitive to changes in both the [Ca2+]o and
      holding potential. Steady-state inactivation was half maximal at a holding
      potential of -60 mV. Ba2+ was a more effective charge carrier than Ca2+ through
      the alpha 1B-1 alpha 2b beta 1-2 Ca2+ channel and combinations of both Ba2+ and
      Ca2+ as charge carriers resulted in the anomalous mole fraction effect. Ca2+
      influx into transfected HEK293 cells was irreversibly inhibited by omega
      conotoxin-GVIA (omega-CgTx-GVIA; 10 nM-1 microM) and omega-conotoxin-MVIIA; 100
      nM-1 microM) whereas 1 microM) whereas no reductions were seen with agents which
      block P or L-type Ca2+ channels. The inorganic ions, gadolinium (Gd3+), cadmium
      (Cd2+) and nickel (Ni2+) reduced the ICa under voltage-clamp conditions in a
      concentration-dependent manner. The order of potency of the three ions was Gd3+ >
      Cd2+ > Ni2+. These experiments suggest that the cloned and expressed alpha 1B-1
      alpha 2b beta 1-2 Ca2+ channel subunits form channels in HEK293 cells that
      exhibit properties consistent with the activity of the native-N-type VDCC
      previously described in neurons.

PMID- 8532143
TI  - Identification and characterization of guanine nucleotide-sensitive melatonin
      receptors in chicken brain.
AB  - Specific melatonin receptors present in crude membrane preparations of chicken
      forebrain were identified by specific binding activity of 2-[125I]iodomelatonin
      and melatonin-dependent inhibition of forskolin-stimulated adenylate cyclase
      activity by a pertussis toxin-sensitive mechanism. The membrane-bound melatonin
      receptors were successfully solubilized with digitonin, and the ligand binding
      activity was shown to be preserved in solubilized membranes when compared with
      that of crude membranes. In both fractions, melatonin receptors consisted of two
      binding components with picomolar and nanomolar affinity. The ligand binding
      activity of solubilized receptors was decreased after treatment with guanine
      nucleotides, and guanosine 5'-(gamma-thio)triphosphate (GTP gamma S) induced a
      transformation of the high affinity receptors to low affinity state. Moreover,
      [35S]GTP gamma S was indicated to bind to solubilized membranes in a melatonin
      dependent fashion. These results demonstrate the existence of functional
      melatonin receptors--G proteins coupling in digitonin-solubilized membranes of
      chicken forebrain membranes.

PMID- 8532144
TI  - Dopamine-induced reduction in the density of guanine nucleotide-sensitive D1
      receptors in human postmortem brain in the absence of apparent D1: D2
      interactions.
AB  - The effects of dopamine and guanine nucleotides on the binding of the D1 dopamine
      receptor antagonist ligand [3H]SCH 23390 were examined in membranes prepared from
      putamen, caudate and nucleus accumbens of human postmortem brain. Dopamine
      induced a concentration-dependent decrease in the apparent maximum number of
      binding sites (Bmax) in each brain region studied, and displaced binding in a
      biphasic manner consistent with the presence of both high and low affinity states
      of the D1 receptor; the GTP analogue Gpp(NH)p transformed this biphasic
      displacement to a monophasic pattern consistent with a shift of high affinity
      sites to a low affinity state. However, the selective D2 antagonist eticlopride
      did not reverse the action of dopamine to decrease Bmax. These data suggest that
      dopamine decreases Bmax for D1 receptors through a high affinity, guanine
      nucleotide-sensitive agonist binding site, but fail to reveal D1:D2 interactions
      at this synaptic level.

PMID- 8532146
TI  - Central alpha 1-adrenoceptors mediate the pressor response to
      intracerebroventricular injection of noradrenaline in unanesthetized rats.
AB  - The intracerebroventricular (i.c.v.) administration of noradrenaline (NA) caused
      dose-dependent blood pressure increases in unanesthetized rats with an ED50 of 35
      nmol. Similar pressor responses were observed after the i.c.v. injection of the
      more selective alpha 1-agonists ST-91, methoxamine and phenylephrine with ED50 of
      60, 155 and 575 nmol, respectively. The maximal pressor response was 57 +/- 3
      mmHg. No tachyphylaxis was observed when injections of 37.5 nmol of NA was i.c.v.
      injected at an interval of 24 hr. No significant differences were observed in the
      plasma content of NA and adrenaline at the peak of the pressor response to i.c.v.
      injected NA when compared to i.c.v. injections of saline. The pressor effects of
      NA were blocked by the i.c.v. pretreatment with prazosin or yohimbine with ID50
      of 0.9 and 29 nmol, respectively. Prazosin was 32-fold more potent than yohimbine
      in blocking the effect of i.c.v. NA, suggesting the involvement of alpha 1
      adrenoceptors in the central mediation of the pressor response to NA. Intravenous
      injections of 13 nmol of prazosin or 90 nmol of yohimbine did not affect the
      pressor response to i.c.v. NA, further indicating the central nervous system
      nature of the response.

PMID- 8532145
TI  - Behavioural and neurochemical effects of OPC-14597, a novel antipsychotic drug,
      on dopaminergic mechanisms in rat brain.
AB  - OPC-14597 is a new antipsychotic drug with a unique pharmacological profile. In a
      behavioural study in rats OPC-14597 did not show cataleptogenic activity even at
      the highest dose (40 mg/kg, i.p.), whereas it antagonized apomorphine-induced
      stereotypy dose-dependently (0.5-40 mg/kg). In vivo microdialysis showed that
      extracellular dopamine (DA) in the striatum was decreased significantly after OPC
      14597 administration at higher doses of 10 and 40 mg/kg. Similar results were
      obtained in extracellular dopamine concentration in the frontal cortex, although
      the changes in DOPAC and HVA concentrations were smaller than those in the
      striatum. OPC-14597 also antagonized DA increase induced by the DA autoreceptor
      antagonist (+)-AJ76. These results that OPC-14597 acts either as an antagonist at
      postsynaptic dopamine receptors or as an agonist at presynaptic dopamine
      autoreceptors.

PMID- 8532147
TI  - Tissue distribution, metabolism and effects of bufotenine administered to rats.
AB  - Bufotenine (N, N-dimethyl-5-hydroxytryptamine) is a serotonin analog reported to
      be hallucinogenic. Bufotenine concentrations were measured by liquid
      chromatography with electrochemical detection after the s.c. injection of
      bufotenine (1, 30 or 100 mg/kg) into rats. At 1 hr, bufotenine was high in lung,
      heart and blood and lower in brain and liver. No N-monomethyl-5-hydroxytryptamine
      was detected, but 5-hydroxyindoleacetic acid (5HIAA) was increased due to
      bufotenine metabolism. Bufotenine disappeared nearly completely by 8 hr.
      Bufotenine concentrations were slightly higher in hypothalamus and brain stem
      than in striatum or cortex; serotonin was slightly decreased, and 5HIAA was
      increased in these brain regions. Pargyline reduced concentrations of 5HIAA in
      blood and tissues after bufotenine injection; LY51641 but not deprenyl mimicked
      pargyline, suggesting type A not type B monoamine oxidase metabolizes bufotenine.
      Bufotenine injection increased serum corticosterone concentration, an effect not
      blocked by metergoline at a dose that blocked a similar increase elicited by
      quipazine. Although only 2% of the serotonin was found in platelet-poor plasma,
      more than 99% of the bufotenine was found in platelet-poor plasma, indicating
      that bufotenine is not stored in platelets. These experiments indicate that
      bufotenine is rapidly eliminated, in part by type A monoamine oxidase, after its
      injection into rats and that bufotenine penetrates the blood-brain barrier
      poorly.

PMID- 8532148
TI  - Attenuation of CCK-induced aversion in rats on the elevated x-maze by the
      selective 5-HT1A receptor antagonists (+) WAY100135 and WAY100635.
AB  - The present study determined the effect of pretreatment with "silent" selective 5
      HT1A receptor antagonists on cholecystokinin (CCK)-mediated effects on rat
      behaviour in the elevated x-maze model of anxiety. In the absence of 5-HT1A
      receptor antagonists, non-sulphated cholecystokinin-octapeptide (CCK-8ns; 10 and
      50 micrograms/kg, i.p.; 30 min prior to testing) produced an anxiogenic profile
      of behaviour on the x-maze, reducing the number of open arm entries and the
      number of exploratory head dips, while increasing the level of risk-assessment as
      measured by the number of stretched-attend postures. CCK-8ns did not, however,
      alter ambulatory activity. Two 5-HT1A receptor antagonists were employed in these
      experiments: (+)WAY100135 (the active enantiomer of N-tert-butyl-3-(4-(2
      methoxyphenyl)piperzin-1-yl)- 2-phenylpropronamine) [sequence: see text] and
      WAY100635 (N-[2-[4(2-methoxyphenyl)-1-piperazinyl-1-piperazinyl]-N-2-
      pyridinyl)cyclohexanecarbonate [sequence: see text] trihydrochloride). When
      administered 10 min prior to CCK-8ns, (+) WAY100135 and 0.3 mg/kg s.c.)
      significantly attenuated profile of CCK-8ns. (+)WAY100135 was also demonstrated
      to significantly inhibit postsynaptic 5-HT1A receptor-mediated 8-OH-DPAT (8
      hydroxy-2-(di-N-propylamino)tetralin)-induced 5-HT syndrome at the same dose used
      in the x-maze experiment. Neither (+)WAY100135 nor WAY100635 had any affects on
      ambulatory activity. These results support a CCK/5-HT1A receptor interaction in
      the modulation of aversion in rats exposed to the elevated x-maze.

PMID- 8532149
TI  - On the mechanism of long-term potentiation induced by (1S,3R)-1-aminocyclopentane
      1,3-dicarboxylic acid (ACPD) in rat hippocampal slices.
AB  - We have reported previously that transient application of a specific metabotropic
      glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate
      (ACPD) can induce a slow-onset form of long-term potentiation (LTP) of synaptic
      transmission in the CA1 region of rat hippocampal slices [Bortolotto Z. A. and
      Collingridge G. L. (1993) Neuropharmacology 32, 1-9]. Here we have investigated
      further the mechanisms involved in the induction and expression of ACPD-induced
      LTP. Unless otherwise stated, field excitatory postsynaptic potentials (EPSPs)
      were recorded in stratum radiatum in response to low frequency (0.033 Hz
      stimulation) of the Schaffer collateral-commissural pathway and 10 microM ACPD
      was added for 20 min to the perfusate. ACPD-induced LTP was still observed
      following blockade of GABAA receptor-mediated synaptic inhibition using
      picrotoxin (50 microM) and was not the result of a change in the presynaptic
      fibre volley. Intracellular recording from area CA1 revealed an increase in the
      size of the EPSP but no associated change in membrane potential or input
      resistance. However, ACPD-induced potentiation was never seen when intracellular
      electrodes contained the Ca(2+)-chelating agent 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA; 0.5 M). In area CA3, ACPD elicited a slow
      onset LTP of the intracellularly recorded EPSP, evoked by stimulation of
      associational fibres. In contrast to area CA1, 10 microM ACPD depolarized CA3
      neurones. Unlike certain other forms of tetanus- and chemically-induced
      potentiation, ACPD-induced LTP was not affected by the L-type Ca2+ channel
      antagonist nimodipine (50 microM). It was, however, prevented by delivering low
      frequency stimulation (900 shocks at 1 Hz) immediately following termination of
      the application of ACPD; an effect which was inhibited by the specific N-methyl-D
      aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate (AP5; 50
      microM). ACPD failed to induce LTP of pharmacologically-isolated NMDA receptor
      mediated EPSPs. The induction of ACPD-induced LTP was blocked by the alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), in a reversible manner. In slices in which
      area CA3 had been removed ACPD failed to induce LTP when applied alone or
      together with AMPA. However, a slow-onset form of LTP was induced, in slices
      lacking area CA3, when a tetanus (100 Hz, 1 sec) was delivered in the presence of
      ACPD and 50 microM AP5 (the latter applied to prevent conventional tetanus
      induced LTP). ACPD-induced LTP was associated with a parallel increase in the
      sensitivity of CA1 neurones to AMPA. Considered together, these data suggest that
      ACPD-induced LTP is due to a direct increase in the AMPA receptor-mediated
      synaptic conductance and involves postsynaptic induction and expression
      mechanisms.

PMID- 8532150
TI  - Pharmacology of metabotropic glutamate receptor-mediated enhancement of responses
      to excitatory and inhibitory amino acids on rat spinal neurones in vivo.
AB  - Using the technique of microelectrophoresis on spinal neurones in pentobarbitone
      anaesthetized rats, (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylate (1S,3R-ACPD)
      reversibly and dose-dependently enhanced responses to alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionate (AMPA), kainate, N-methyl-D-aspartate (NMDA) and L
      glutamate to a similar extent. 1S,3R-ACPD also enhanced inhibitory responses to
      both glycine and gamma-aminobutyrate (GABA). Such results are consistent with a
      metabotropic glutamate receptor-mediated decrease in membrane conductance. 1S,3R
      ACPD was the most active metabotropic agonist tested for these effects; the rank
      order of activity was: 1S,3R-ACPD > or = (2S,3S,4S)alpha-(carboxycyclopropyl)
      glycine(L-CCG-l) > (R, S)-3,5-dihydroxy-phenylglycine (3,5-DHPG) > (S)
      homoquisqualate > quisqualate = 1S,3S-ACPD > L-2-amino-4-phosphonobutyrate (L
      AP4) > 1R,3S-ACPD. These effects of 1S,3R-ACPD were antagonized by (RS)-alpha
      methyl-4-carboxy-phenylglycine (M4CPG) and (S)-4-carboxy-3-hydroxy-phenylglycine
      (4C3HPG) but not by (S)-4-carboxy-phenylglycine (4CPG) or L-amino-3-phosphono
      propionate (L-AP3). The pharmacology of the actions of mGluR agonists and
      antagonists on rat spinal neurones in vivo does not obviously correlate with the
      published pharmacology of a single cloned metabotropic glutamate receptor subtype
      but rather suggests that both Group 1 and 2 receptors contribute to the above
      effects.

PMID- 8532151
TI  - Interactions between metabotropic and ionotropic glutamate receptor agonists in
      the rat spinal cord in vivo.
AB  - Microelectrophoretic application of the non-selective metabotropic glutamate
      receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid
      [(1S,3R)-ACPD] and the group I selective mGluR agonist (RS)-3,5
      dihydroxyphenylglycine [(RS)-3,5-DHPG] potentiated the responses of rat spinal
      neurones to the cyclically-ejected ionotropic excitatory amino acid (EAA)
      agonists NMDA, AMPA and kainate in vivo. Potentiation was not selective between
      the three ionotropic responses and was paralleled by an enhancement of background
      activity in spontaneously active cells. "Correcting" spike count data for this
      increase in background activity showed that the EAA responses were not
      potentiated beyond the apparent enhancement of cell excitability. Neither mGluR
      agonist produced potentiation when NMDA/AMPA cycling was superimposed on
      background discharge held constant with kainate. It is concluded that
      potentiation produced by both (1S,3R)-ACPD and (RS)-3,5-DHPG is secondary to an
      enhancement of cell excitability rather than being due to a specific interaction
      with ionotropic EAA receptors. The mechanism of excitability enhancement cannot
      be determined by extracellular recording, but group I mGluRs are most likely to
      be responsible.

PMID- 8532152
TI  - The involvement of metabotropic glutamate receptors and their intracellular
      signalling pathways in sustained nociceptive transmission in rat dorsal horn
      neurons.
AB  - The excitatory responses of individual dorsal horn neurons to cutaneous brush,
      repeated application of the C-fibre-selective chemical algogen, mustard oil, or
      to ionophoretic (1S,3R)-ACPD [a metabotropic glutamate receptor (mGluR) agonist]
      were monitored by extracellular recording. We have previously shown that the
      responses of dorsal horn neurons to mustard oil are inhibited by several
      selective antagonists of mGluRs. Effects of ionophoresis of the mGluR antagonists
      (R,S)-CHPG and L-AP3 and a range of selective inhibitors of intracellular
      signalling pathways were examined on evoked responses here. The results suggest
      that protein kinase C, phospholipase A2 and perhaps Ca2+/calmodulin kinase II
      play a role in mediating the sustained elevated activity of dorsal horn neurons
      that is incrementally elicited by repeated application of mustard oil, but
      probably make little contribution to sustained brush-evoked activity. Concurrence
      in the sensitivity of mustard oil- and (1S,3R)-ACPD-evoked activity to (R,S)
      CHPG, L-AP3 and to inhibitors of intracellular signalling pathways, suggests that
      mGluRs are an important origin of these intracellular signals required for
      sustained nociception.

PMID- 8532153
TI  - Modulation of sensory neurone excitatory and inhibitory responses in the
      ventrobasal thalamus by activation of metabotropic excitatory amino acid
      receptors.
AB  - Several different types of metabotropic excitatory amino acid receptors (mGluRs)
      are present in the thalamus. We have previously shown that the agonists L-AP4 and
      CCG-I can have apparently presynaptic effects on GABAergic inhibitory
      transmission in the thalamus. In this study we attempted to characterize the
      different receptor types which may mediate these effects and the known post
      synaptic excitatory actions of 1S,3R-ACPD in the ventrobasal thalamus, by using a
      number of agonists with different spectra of activity at the various mGluRs.
      Inhibitory responses in ventrobasal thalamic neurones of urethane-anaesthetized
      rats were evoked by air-jet stimuli to the vibrissae and extracellular recording
      methods were used to reveal inhibitory responses as an inhibition of excitatory
      responses in a condition-test paradigm. The Group II and Group III mGluR agonists
      L-AP4, CCG-I, DCG-IV, 1S,3R-ACPD and S-4C3HPG, applied in the vicinity of the
      recording site by iontophoresis, were found to reduce inhibitions revealed by the
      condition-test paradigm (by 67, 75, 50, 43 and 77% from control inhibitions,
      respectively). The endogenous mGluR agonist L-serine-O-phosphate (L-SOP) was
      found to have similar, although weaker, actions (31% reduction of inhibition),
      while the Group I agonist 3,5-DHPG had little effect in this test (9% reduction
      of inhibition). In contrast, both 3,5-DHPG and 1S,3R-ACPD had direct excitatory
      actions on VB neurones, and these could be antagonized by 4CPG. The effects of
      CCG-I in the condition-test paradigm could be antagonized by the antagonists
      MCCG, MCPG, but not MAP4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532154
TI  - The effects of L-AP4 and L-serine-O-phosphate on inhibition in primary
      somatosensory cortex of the adult rat in vivo.
AB  - The effects of two iontophoretically applied Group III mGluR agonists were
      studied on the inhibition in neocortex produced by natural stimulation of
      vibrissae. The agonists L-AP4 and L-serine-O-phosphate (L-SOP) were shown to
      produce qualitatively similar effects on the inhibition. Forty-four percent of
      neurones (total n = 57) displayed disinhibition during application of the
      agonists. The disinhibitory effects often outlasted the offset of the agonist
      application by at least 10 min. Concurrent application of the mGluR antagonist
      (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG) appeared to reverse the
      disinhibitory effects of L-AP4 and L-SOP in 3 out of 5 neurones tested. However
      (+)-MCPG itself was found to have disinhibitory effects in some neurones. Some
      neurones (n = 7) showed increases in inhibition during either L-AP4 or L-SOP
      application. These appeared most pronounced in those neurones where the initial
      (pre-drug) inhibition was minimal, perhaps suggesting that the agonists were
      disinhibiting a local disinhibition. The data obtained in the experiments suggest
      that the disinhibitory effects are mediated by a heteroreceptor on inhibitory
      terminals, action at which depresses the release of inhibitory transmitter. The
      possible role of the modulation of inhibition by presynaptic mGluRs is discussed.

PMID- 8532155
TI  - Induction or protection of limbic seizures in mice by mGluR subtype selective
      agonists.
AB  - The behavioral consequences of metabotropic glutamate receptor (mGluR) activation
      were investigated following intracerebral administration of the mGluR selective
      agonists (RS)3,5-dihydroxyphenyl-glycine (3,5-DHPG), (1S,3R)-1-aminocyclopentane
      1,3-dicarboxylate (1S,3R-ACPD), (1R,3S)-1-aminocyclopentane-1,3-dicarboxylate
      (1R,3S-ACPD), L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP)
      and (2S,3S,4S)alpha-(carboxycyclopropyl)glycine (L-CCGI) into the thalamus in
      mice. Injections of 3,5-DHPG, 1S,3R-ACPD and L-CCGI produced dose-dependent
      increases in limbic seizures with a potency order of 3,5-DHPG = 1S,3R-ACPD > L
      CCGI. This effect of 1S,3R-ACPD was stereoselective, since the inactive isomer
      (1R,3S-ACPD) did not elicit seizure activity. Limbic seizures induced by the
      phosphoinositide-coupled mGluR subtype selective agonist 3,5-DHPG were attenuated
      by the mGluR antagonist L-2-amino-3-phosphonopropanoic acid (L-AP3) and
      dantrolene, inhibitors of mGluR-mediated intracellular calcium mobilization.
      Interestingly, L-AP4, L-SOP and low doses of L-CCGI also protected against 3,5
      DHPG seizures. These data indicate that mGluR agonist-induced limbic seizures in
      mice are mediated by activation of phosphoinositide-coupled mGluRs. Furthermore,
      these seizures can be protected against by activation of mGluRs that are
      negatively-linked to cAMP formation.

PMID- 8532156
TI  - Blockade of the second messenger functions of the glutamate metabotropic receptor
      is associated with degenerative changes in the retina and brain of immature
      rodents.
AB  - Activation of metabotropic glutamate receptors (mGluR) by Glu or related mGluR
      agonists triggers phosphoinositide (PI) hydrolysis, intracellular Ca2+
      mobilization and protein kinase C activation. These mGluR agonist-stimulated
      events are inhibited strongly by 2-amino-3-phosphono-L-propionic acid (L-AP3) and
      L-aspartate-beta-hydroxamate (L-A beta H), and much more weakly by D-AP3 and L
      serine-O-phosphate (L-SOP). Daily s.c. administration of DL-AP3 subchronically to
      infant rodents causes the developing retina and optic nerves to degenerate. In
      the present study, we describe the evolution of the cytopathological reaction in
      the developing rodent retina following DL-AP3 treatment and show that DL-AP3 can
      induce similar cytopathological changes in several regions of the immature rodent
      brain. In addition, we show that the retinotoxic action of DL-AP3 is mimicked by
      L-A beta H but not by L-SOP, and that L-AP3 is a much stronger retinotoxin that D
      AP3. These observations suggest a possible mechanistic link between the PI
      hydrolysis blocking action and retinotoxic action. Our findings are consistent
      with the hypothesis that under normal physiological circumstances, the Glu
      metabotropic receptor through its PI-hydrolysis-linked second messenger functions
      provides vitally important support for developing neurons, and that disruption of
      this support can cause widespread neuronal degeneration.

PMID- 8532157
TI  - The inhibitory mGluR agonist, S-4-carboxy-3-hydroxy-phenylglycine selectively
      attenuates NMDA neurotoxicity and oxygen-glucose deprivation-induced neuronal
      death.
AB  - We examined the effect of two novel phenylglycine derivative drugs on
      excitotoxicity in murine cortical cell cultures: S-4-carboxy-3-hydroxy
      phenylglycine (4C3HPG), a selective agonist of mGluRs 2/3 and an antagonist at
      mGluRs 1/5, and S-3 hydroxy-phenylglycine (3HPG), an agonist of mGluRs 1/5.
      4C3HPG attenuated slowly-triggered NMDA-induced excitotoxic neuronal death, as
      well as the death induced by combined oxygen-glucose deprivation, but did not
      affect slowly-triggered excitotoxicity induced by AMPA or kainate. As expected,
      4C3HPG also reduced NMDA-induced increases in cAMP in near-pure neuronal
      cultures, and the protective effect of 4C3HPG on NMDA toxicity could be reversed
      by adding 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic-monophosphate (CPT cAMP)
      to the exposure medium. In contrast, 3HPG did not did not have any protective
      effects in these paradigms; in fact, slowly-triggered NMDA-induced excitotoxicity
      and the neuronal cell death induced by oxygen-glucose deprivation were
      potentiated. These results are consistent with the idea that the "inhibitory"
      mGluRs 2/3 exert a negative modulatory action on NMDA receptor-mediated
      excitotoxicity via reduction in neuronal cAMP levels.

PMID- 8532158
TI  - Activation of metabotropic glutamate receptors coupled to inositol phospholipid
      hydrolysis amplifies NMDA-induced neuronal degeneration in cultured cortical
      cells.
AB  - We have studied the influence of class I metabotropic glutamate receptors
      (mGluRs) on excitotoxic neuronal degeneration in cultured murine cortical neurons
      grown on a monolayer of astrocytes. These cultures expressed high levels of
      mGluR5 mRNA, which were comparable to those found in RNA extracts from cerebral
      cortex. Cortical neurons in mixed cultures were heavily stained with antibodies
      raised against mGluR5 and were also stained--albeit to a much lower extent--with
      mGluR1a but not with mGluR1b or c antibodies. Preferential agonists of class I
      mGluRs, such as quisqualate, 3,5-dihydroxyphenylglycine (DHPG), and trans
      azetidine-2,4-dicarboxylic acid (t-ADA), as well as the mixed mGluR agonist,
      1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) all stimulated PPI
      hydrolysis in cultured cortical cells. The potency of N-methyl-D-aspartate (NMDA)
      in inducing neuronal degeneration was substantially enhanced when the drug was
      coincubated with quisqualate, DHPG or t-ADA during a 10-min pulse (paradigm of
      "fast" toxicity). None of the mGluR agonists influenced neuronal viability by
      itself. The amplification of NMDA toxicity by quisqualate or DHPG was attenuated
      by a series of protein kinase C (PKC) inhibitors, suggesting that class I mGluRs
      operate, at least in part, through activation of PKC. Quisqualate and, in
      particular, DHPG enhanced excitoxic neuronal degeneration even when applied after
      the toxic pulse with NMDA. This action is likely to occur early in the maturation
      of excitotoxic damage, because the functional activity of class I mGluRs was
      substantially reduced at 2 or 3 hr after the NMDA pulse. These results suggest
      that activation of class I mGluRs enhances NMDA-receptor mediated neuronal
      toxicity and encourage the search for selective antagonists for the experimental
      therapy of acute or chronic neurodegenerative diseases.

PMID- 8532159
TI  - Pharmacological characterization of MCCG and MAP4 at the mGluR1b, mGluR2 and
      mGluR4a human metabotropic glutamate receptor subtypes.
AB  - The two reported metabotropic glutamate receptor (mGluR) antagonists, alpha
      methyl-cyclopropyl glycine (MCCG) and alpha-methyl-aminophosphonobutyrate (MAP4)
      were tested on the mGluR1b, mGluR2 and mGluR4a subtypes of human mGluRs. Neither
      MCCG (500 microM) nor MAP4 (500 microM) antagonized the activation of mGluR1b by
      10 microM quisqualate. MCCG was found to potently antagonize the action of 30
      microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] at mGluR2
      (IC50 = 87.5 microM; apparent Kd = 25 microM) but did not block the action of 1
      microM S-2-amino-4-phosphonobutyric acid at mGluR4a (IC50 >> 1 mM). MAP4 was
      found to be a weak antagonist or partial agonist at mGluR4a (IC50 > 500 microM)
      and, less potently, also antagonized the action of 30 microM (1S,3R)-ACPD) at
      mGluR2 (IC50 approximately 2 mM).

PMID- 8532160
TI  - 1S,3R-ACPD dose-dependently induces a slow-onset potentiation in the rat
      hippocampal CA1 region in vivo.
AB  - It has been reported that application of 1S,3R-1-aminocyclopentane 1,3
      dicarboxylic acid (ACPD) in vitro triggers a slow-onset potentiation in the
      hippocampal CA1 region. This study examined the effect of ACPD in the CA1 of
      freely moving rats. No effect on fEPSP baseline recordings occurred at 40 and 400
      microM/5 microliters, however at 4 mM/5 microliters ACPD induced a slow-onset
      potentiation. MCPG (200 mM/5 microliters) completely inhibited this ACPD effect.
      These results indicate that slow-onset potentiation in the CA1 region, also
      occurs in vivo.

PMID- 8532161
TI  - Metabotropic glutamate receptor agonist trans-azetidine-2,4-dicarboxylic acid
      facilitates maintenance of LTP in the dentate gyrus in vivo.
AB  - We examined the role of metabotropic glutamate receptors by studying the effect
      of intracerebroventricular infusion of the putative mGluR agonist trans-azetidine
      2,4-dicarboxylic acid (tADA) on long-term potentiation (LTP) in the dentate gyrus
      of freely moving rats. Weak tetanization caused a decremental potentiation which
      returned to baseline levels within 2 hr. Injections of tADA (20 mM/5 microliters)
      30 min prior to weak tetanization prolonged LTP of the field EPSP for at least 24
      hr.

PMID- 8532162
TI  - Pharmacological tools for the investigation of metabotropic glutamate receptors
      (mGluRs): phenylglycine derivatives and other selective antagonists--an update.
AB  - Glutamate is known to produce many of its pre- and post-synaptic effects through
      interaction with at least three groups of G-protein-coupled metabotropic
      receptors. While molecular biological approaches have revealed a great deal about
      the nature of these receptors and their neuroanatomical localization, elucidation
      of their role in both physiological and pathological processes has been hampered
      by the lack of appropriate pharmacological agents. However, the situation is
      rapidly changing with the discovery of antagonist phenylglycine derivatives, and
      other compounds. Not only is it now possible to discriminate between the
      individual metabotropic glutamate receptor groups but, in several cases, between
      individual group members. The future development of potent and subtype-specific
      antagonists will greatly facilitate the advancement of our understanding of these
      receptors as well as providing the potential for novel therapeutic approaches in
      a variety of neuropathological states.

PMID- 8532163
TI  - Novel agonists for metabotropic glutamate receptors: trans- and cis-2-(2-carboxy
      3-methoxymethylcyclopropyl)glycine (trans- and cis-MCG-I).
AB  - New derivatives of 2-(carboxycyclopropyl)glycine (CCG), (2S,1'S,2'R,3'S)- and
      (2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl) glycine (trans- and cis
      MCG-I), effectively inhibited forskolin-stimulated cyclic AMP formation in a
      concentration dependent manner in cultured spinal neurones of rats. They
      effectively depressed monosynaptic excitation in the spinal reflex of newborn
      rats with IC50 values of 0.3 and 3 microM, respectively, which was sensitive to
      (+)-MCPG. They did not cause any depolarization even when the concentration was
      increased up to 0.3 mM. However, after treatment with quisqualate, cis-MCG-I
      caused a depolarization of motoneurones in the newborn rat spinal cord in a
      concentration dependent manner with a threshold concentration of 1 microM
      (quisqualate effect). The depolarizing activity developed after quisqualate
      treatment gradually decreased but lasted for more than 2 hr. The depolarization
      induced by cis-MCG-I seemed pharmacologically similar to that of phosphonate
      containing analogues of glutamate such as L-AP4 or L-AP6 under the "quisqualate
      effect". These novel CCG derivatives would be expected to provide useful probes
      for elucidating the physiological function of mGluRs.

PMID- 8532164
TI  - Effects of quisqualic acid analogs on metabotropic glutamate receptors coupled to
      phosphoinositide hydrolysis in rat hippocampus.
AB  - L-Glutamic acid (L-Glu) and L-aspartic acid (L-Asp) activate several receptor
      subtypes, including metabotropic Glu receptors coupled to phosphoinositide (PI)
      hydrolysis. Quisqualic acid (Quis) is the most potent agonist of these receptors.
      There is evidence that activation of these receptors may cause a long lasting
      sensitization of neurons to depolarization, a phenomenon called the Quis effect.
      The purpose of the current studies was to use Quis analogs and the recently
      identified metabotropic receptor antagonist, (+)-alpha-methyl-4-carboxy
      phenylglycine((+)-MCPG), to define the structural properties required for
      interaction with the metabotropic receptors coupled to PI hydrolysis and to
      determine if the Quis effect is mediated by these receptors. The effects of Quis
      analogs on PI hydrolysis were studied in the absence or presence of the
      metabotropic receptor-specific agonist 1SR,3RS-1-amino-1,3
      cyclopentanedicarboxylic acid (1SR,3RS-ACPD) in neonatal rat hippocampus. Some of
      the compounds that induce the Quis effect also stimulate PI hydrolysis, including
      Quis itself and 9 (homoquisqualic acid). Not all of the Quis analogs that
      stimulate PI hydrolysis, however, induce the Quis effect, including 7A (EC50 =
      750 +/- 150 microM) and (RS)-4-bromohomoibotenic acid (BrHI) (EC50 = 130 +/- 40
      microM). Although (+)-MCPG blocked PI hydrolysis stimulated by Quis (IC50 = 370
      +/- 70 microM), it had no effect on the induction of the Quis effect. Other Quis
      analogs did not stimulate PI hydrolysis but rather blocked the effects of 1SR,3RS
      ACPD. The IC50 values were 240 +/- 70 microM for 2, 250 +/- 90 microM for 3, and
      640 +/- 200 microM for 4. Data for inhibition by 2 and 3 were consistent with non
      competitive mechanisms of action. These studies provide new information about the
      structural features of Quis required for interaction with metabotropic receptors
      coupled to PI hydrolysis and provide evidence that the Quis effect is not
      mediated by (+)-MCPG sensitive subtypes of these receptors.

PMID- 8532165
TI  - Selective inhibition of forskolin-stimulated cyclic AMP formation in rat
      hippocampus by a novel mGluR agonist, 2R,4R-4-aminopyrrolidine-2,4-
      dicarboxylate.
AB  - Metabotropic glutamate receptors (mGluRs) are a heterogeneous family of G-protein
      coupled receptors that are linked to multiple second messengers in the rat
      hippocampus. The compound 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R
      ACPD) has been widely used to activate this class of receptors and study their
      functions in situ. However, 1S,3R-ACPD acts on multiple mGluR subtypes to produce
      multiple alterations in second messengers. We report here that the aza
      substituted analog of 1S,3R-ACPD, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate
      (2R,4R-APDC), is a highly selective agonist for negatively-coupled cAMP-linked
      mGluRs in the rat hippocampus, with similar potency in mGluR2 expressing cells.
      1S,3R-ACPD decreases forskolin-stimulated cAMP formation, increases basal cAMP
      formation, and increases phosphoinositide hydrolysis in the rat hippocampus.
      However, 2R,4R-APDC inhibited forskolin-stimulated cAMP, but had none of the
      other activities of 1S,3R-ACPD. Furthermore, 2R,4R-APDC had no measurable
      ionotropic glutamate receptor affinity in rat hippocampus, as indicated by lack
      of effects on basal and glutamate agonist-evoked [3H]norepinephrine release.
      2R,4R-APDC also inhibited forskolin-stimulated cAMP formation in human mGluR2
      expressing cells with about three-fold greater potency than 1S,3R-ACPD, but
      unlike 1S,3R-ACPD, showed no appreciable activation of phosphoinostide hydrolysis
      in human mGluR1 alpha expressing cells. Thus, 2R,4R-APDC should be a useful
      pharmacological agent to explore the functions of mGluRs coupled to inhibition of
      adenylate cyclase.

PMID- 8532166
TI  - New phenylglycine derivatives with potent and selective antagonist activity at
      presynaptic glutamate receptors in neonatal rat spinal cord.
AB  - The depression of the monosynaptic excitation of neonatal rat motoneurones
      produced by the metabotropic glutamate receptor (mGluR) agonists (1S,3S)-1
      aminocyclopentane-1, 3-dicarboxylate (ACPD) or L-2-amino-4-phosphonobutyrate (L
      AP4) was antagonized by three novel phenylglycine analogues: (RS)-alpha-methyl-4
      sulphonophenylglycine (MSPG), (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG)
      and (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG). The potencies of all the
      new compounds were greater than that of the previously reported (RS)-alpha-methyl
      4-carboxyphenylglycine (MCPG). For L-AP4-sensitive presynaptic mGluRs, the order
      of antagonist potency found was MPPG > MSPG > MTPG > MCPG. In contrast, the order
      of antagonist potency found for (1S,3S)-ACPD-sensitive presynaptic mGluRs was
      MTPG > MPPG > MSPG > MCPG. To date, MPPG (KD 9.2 microM) is the most potent L-AP4
      sensitive receptor antagonist yet tested on the neonatal rat spinal cord. In
      addition, MTPG (KD 77 microM) is the most potent antagonist yet tested for
      (1S,3S)-ACPD-sensitive receptors in this preparation.

PMID- 8532167
TI  - The actions of a range of excitatory amino acids at (1S,3R)-1-aminocyclopentane
      1,3-dicarboxylic acid-depolarizing receptors on neonatal rat motoneurones.
AB  - Depolarizations induced by a range of amino acids including some sulphur
      containing excitatory transmitter candidates were evoked from motoneurones in the
      neonatal rat spinal cord under conditions that precluded activation of known
      ionotropic glutamate receptors. The responses could be partially and
      differentially depressed by continuous application of several metabotropic
      glutamate receptor (mGluR) antagonists or by receptor desensitization with the
      mGluR agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD].
      In most cases [the exceptions being (1S,3R)-ACPD and to a lesser extent,
      quisqualate], the major component of these depolarizations was resistant to
      antagonism by phenylglycine-derived mGluR antagonists or desensitization of
      (1S,3R)-ACPD-sensitive receptors. Of the excitatory responses observed with the
      tested agonists, those evoked by L-glutamate itself were generally the least
      affected by blockade of known glutamate receptors.

PMID- 8532168
TI  - Inactivation in vivo of metabotropic glutamate receptor 1 by specific chromosomal
      insertion of reporter gene lacZ.
AB  - Two main classes of glutamate receptors have been characterized, the ionotropic
      (iGluRs) and the metabotropic (mGluRs) glutamate receptors. In order to better
      understand the function of the latter, we have used the technique of gene
      targeting to generate mice in which the mGluR1 subtype has been inactivated. The
      disruption was carried out by homologous recombination in embryonic stem (ES)
      cells at the level of the seven-membrane domain, leaving the extracellular part
      of the receptor untouched. In addition, the reporter gene lacZ was inserted in
      frame with mGluR1 coding sequence within the second intracellular loop of the
      receptor. The transmission of the mutation to the germ line showed first that the
      fusion protein was functional and second that mGluR1 was inactivated. Therefore,
      the way homologous recombination was performed in ES cells demonstrated that gene
      replacement of mGluR1 by lacZ could be a powerful technique to disrupt a gene and
      at the same time study its endogenous expression.

PMID- 8532169
TI  - Molecular and functional characterization of recombinant human metabotropic
      glutamate receptor subtype 5.
AB  - We have isolated and characterized overlapping cDNAs that encode two isoforms of
      the human metabotropic glutamate receptor subtype 5 (hmGluR5). The deduced amino
      acid sequences of human and rat mGluR5a are 94.5% identical. However, a region in
      the putative cytoplasmic domain (SER926-ALA1121) displays significant sequence
      divergence. Genomic analysis of this region showed that the sequence divergence
      results from species-specific differences in the genomic sequences, not from
      alternative splicing. The distribution of mGluR5 mRNA in human brain was most
      strongly detected throughout the hippocampus, with moderate levels in the caudate
      putamen, cerebral cortex, thalamus, and deep cerebellar nuclei, and at low levels
      in the cerebellar cortex. Activation of both hmGluR5a and hmGluR5b transiently
      expressed in Xenopus oocytes and HEK293 cells was coupled to inositol phosphate
      (InsP) formation and elevation of the intracellular free calcium ([Ca2+]i). The
      agonist rank order of potency for activating recombinant hmGluR5a receptors in
      either system was quisqualate > L-glutamate > 1S,3R-ACPD. Both the quisqualate
      stimulated InsP and [Ca2+]i were inhibited by (+)-MCPG. Recombinant human mGluR5a
      was also stably expressed in mouse fibroblast Ltk- cells, in which the efficacy
      and potency of quisqualate were unchanged for more than 30 cell passages.

PMID- 8532170
TI  - Pharmacological analysis of 4-carboxyphenylglycine derivatives: comparison of
      effects on mGluR1 alpha and mGluR5a subtypes.
AB  - The antagonist effects of the 4-carboxyphenylglycines: (S)-4-carboxy
      3hydroxyphenylglycine (4C3HPG), (S)-4-carboxyphenylglycine (4CPG) and (+)-alpha
      methyl-4-carboxyphenylglycine (M4CPG) were compared on functional responses of
      human metabotropic glutamate receptor (mGluR) subtypes mGluR1 alpha and mGluR5a.
      These receptors both belong to group 1 type mGluRs which couple to the
      phosphoinositide (PI) hydrolysis/[Ca2+]i mobilization signal transduction pathway
      and are closely related in both structure and agonist pharmacology. In this
      study, the IC50 values obtained for quisqualate induced PI hydrolysis responses
      show that although all the phenylglycines are antagonists for both mGluR1 alpha
      and mGluR5a, the compounds exhibit differential potencies at these receptor
      subtypes. The 4C3HPG derivative was the most potent antagonist for both mGluR1
      alpha (IC50 range: 19-50 microM) and mGluR5a (IC50 range: 53-280 microM). 4CPG
      produced an IC50 range of 4r-72 microM for mGluR1 alpha and 150-156 microM for
      mGluR5a cells. The potency of the M4CPG could not be distinguished from that of
      4CPG with IC50 ranges of 29-100 microM and 115-210 microM for mGluR1 alpha and
      mGluR5a respectively. Further characterization of the dose-response effects of
      the compounds on quisqualate induced [Ca2+]i mobilization showed that although
      the magnitude of phenylglycine inhibition was reduced for both mGluR subtypes
      compared to those observed for stimulation of PI hydrolysis (except for 4C3HPG on
      mGluR1 alpha), similar differences in the relative potencies of the
      phenylglycines between mGluR1 alpha (IC50s: 40 +/- 10 microM for 4C3HPG: 300-1000
      microM for 4CPG and M4CPG) and mGluR5a (IC50s: > 1000 microM) were
      evident.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532171
TI  - Phenylglycine derivatives discriminate between mGluR1- and mGluR5-mediated
      responses.
AB  - The effects of the phenylglycine derivatives, alpha-methyl-4-carboxyphenylglycine
      (MCPG), 4-carboxyphenylglycine (4CPG), 4-carboxy-3-hydroxyphenylglycine (4C3HPG),
      3-hydroxyphenylglycine (3HPG) and 3,5-dihydrohyphenylglycine (DHPG) were tested
      on LLC-PK1 cells transiently expressing the rat mGluR1a or mGluR5a receptors. As
      previously reported by others, (S)-3HPG and (RS)-DHPG were found to be partial
      agonists at mGluR1a, whereas(+)-MCPG,(S)-4CPG and (S)-4C3HPG competitively
      antagonized the effect of Glu. Surprisingly, the 4-carboxy derivatives of
      phenylglycine antagonized the effect of 1S,3R-ACPD on mGluR1a with lower KB
      values. On mGluR5a, (S)-3HPG and (RS)-DHPG are also partial agonists. However, in
      contrast to their effects on mGluR1a,(S)-4CPG did not inhibit the effect of Glu
      or 1S,3R-ACPD, and (S)-4C3HPG acted as an agonist at high concentration. Whereas
      no significant antagonism of the Glu effect on mGluR5a was observed with 1 mM (+)
      MCPG, this compound was found to potently and competitively antagonize the effect
      of 1S,3R-ACPD. Finally, the effect of 4CPG was also examined on cultured cortical
      and cerebellar neurons that express mGluR5 and mGluR1 mRNA, respectively. 4CPG
      inhibited 1S,3R-ACPD-stimulated IP production in cerebellar neurons only. These
      results(1) demonstrate that phenylglycine derivatives can be used to discriminate
      between effects mediated by mGluR1 and mGluR5 and (2) suggest that the apparent
      potency of phenylglycine antagonists depends on the agonist used to activate
      these receptors.

PMID- 8532172
TI  - 1S,3R-ACPD-preferring inward current in rat dorsolateral septal neurons is
      mediated by a novel excitatory amino acid receptor.
AB  - Metabotropic glutamate receptors (mGluRs) form a receptor family that consists of
      diverse receptor subtypes; now, numbering 8--exclusive of splice variants.
      (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) has been suggested
      to be a selective agonist for the mGluRs. We have recently reported that, in rat
      dorsolateral septal nucleus (DLSN) neurones, a 1S,3R-ACPD-preferring inward
      current (ACPDi) persists in pertussis toxin-treated rats. We now report that this
      ACPDi-current: (1) persists in DLSN neurones dialyzed with a stable analog of
      GTP, namely, GTP gamma S; (2) exhibits a negative slope region with inward
      rectification in its I-V relationship; (3) persists in neurones superfused with
      tetrodotoxin or low calcium solutions; (4) is dependent upon both sodium and
      calcium ions; and (5) is independent of a reduction in temperature. Furthermore,
      pharmacological data suggest that this current may be activated by a unique type
      of excitatory amino acid (EAA) receptor, i.e. a receptor which prefers
      "metabotropic" EAA agonists and is insensitive to AP5 or CNQX. Activation by ACPD
      of inward currents associated with a conductance increase have also been reported
      at cultured mouse cerebellar Purkinje neurones; in slices of rat hippocampal CA1
      neurones and slice cultures of hippocampal CA3 neurones. We suggest that this
      ACPDi current may play an important role within the CNS in the induction of long
      term potentiation and other neurological processes; processes attributed
      previously to currents associated with NMDA receptor activation.

PMID- 8532173
TI  - Co-existence and interaction between facilitatory and inhibitory metabotropic
      glutamate receptors and the inhibitory adenosine A1 receptor in cerebrocortical
      nerve terminals.
AB  - We have investigated the interaction between facilitatory and inhibitory
      metabotropic glutamate receptors (mGluRs) and the inhibitory adenosine A1
      receptor in cerebrocortical nerve terminals from young (3 weeks postnatal) rats.
      The adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA) (1 microM) and the
      mGluR agonist L-2-amino-4-phosphonobutyrate (L-AP4) (100 microM) inhibited Ca(2+)
      dependent release of glutamate evoked by depolarization of synaptosomes with 30
      mM KCl to 33 +/- 6 and 30 +/- 4% of control values, respectively. The CHA and L
      AP4 inhibition of release was consistent with the reduction of a component of
      Ca2+ entry in nerve terminals which was also sensitive to omega-Aga-IVA. When the
      inhibitory agonists were co-applied at optimal concentrations, no additivity of
      the inhibitory effects on either glutamate release or [Ca2+]c was observed. The
      nerve terminals from young rats also exhibit the facilitatory pathway for
      glutamate release that is observed during 4-aminopyridine-evoked depolarization
      after stimulation of mGluRs with the agonist (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylate (ACPD) in the presence of arachidonic acid (AA). The addition of
      ACPD or AA alone did not alter the ability of CHA and L-AP4 to reduce the
      release, however the co-application of AA and ACPD abolished the inhibitory
      effect induced by CHA and L-AP4 whether alone or in combination. These results
      indicate the co-existence of the three modulatory pathways of glutamate release
      and the dominant role of the ACPD/AA activated facilitatory pathway in its
      interaction with the inhibitory pathways activated by L-AP4 and CHA.

PMID- 8532174
TI  - Modulation of calcium channels by metabotropic glutamate receptors in cerebellar
      granule cells.
AB  - We investigated the mechanisms by which metabotropic glutamate receptors (mGluRs)
      modulate specific Ca2+ channels in cerebellar granule cells. A large fraction of
      the current in granule cells is carried by L- and Q-type Ca2+ channels (about 26%
      each), whereas N- and P-type contribute proportionally less to the global current
      (9 and 15%, respectively). l-Aminocyclopentane-dicarboxylate (t-ACPD), (2S,3S,4S)
      alpha-(carboxycyclopropyl)-glycine (L-CCGI) and (S)-4-carboxy-3
      hydroxyphenylglycine [(S)-4C3HPG], but not L(+)-2-amino-4-phosphonobutyrate (L
      AP4) reduced the Ca2+ current amplitude. The t-ACPD-induced inhibition was fully
      antagonized by (+/-)-methyl-4-carboxyphenylglycine [(+/-)-MCPG] and blocked by
      pertussis toxin (PTX). These results are consistent with inhibitory response
      mediated by mGluR2/R3. The use of specific Ca2+ channel blockers provided
      evidence that mGluR2/R3 inhibited both L- and N-type Ca2+ currents. In PTX
      treated cells, Glu or t-ACPD, but not L-CCGI or L-AP4, increased the Ca2+
      current. Consistent with the activation of mGluR1, the antagonists (+)-MCPG and
      (S)-4C3HPG prevented the facilitation of Ca2+ current produced by t-ACPD. The
      mGluR1-activated facilitation was completely blocked by nimodipine, indicating
      that L-type Ca2+ currents were selectively potentiated.

PMID- 8532175
TI  - Metabotropic glutamate receptor modulation of synaptic transmission in
      corticostriatal co-cultures: role of calcium influx.
AB  - Modulation of excitatory glutamatergic transmission at corticostriatal synapses
      by a metabotropic glutamate receptor (mGluR) was examined using a newly developed
      cell culture preparation in which small explants of cortical tissue are grown in
      co-culture with isolated striatal neurons. Electrical stimulation of cortical
      tissue evoked excitatory postsynaptic currents (eEPSCs) observed during tight
      seal, whole-cell recordings from striatal neurons. Transmission was mediated by
      activation of AMPA/kainate-type glutamate receptors. The mGluR agonists, 1SR,3RS
      ACPD and DCG-IV, reduced eEPSC amplitude. The effect of 1SR,3RS-ACPD increased in
      a concentration-dependent manner. Application of phorbol diacetate (PDAc)
      potentiated eEPSC amplitude and reduced the inhibitory effect of mGluR
      activation. Pretreatment with pertussis toxin (PTX) also reduced inhibition by
      1SR,3RS-ACPD. Under conditions in which transmission was independent of the
      function of voltage-gated calcium channels, mGluR activation reduced the
      frequency of occurrence of miniature EPSCs (mEPSCs), but did not alter mEPSC
      amplitude. This effect of mGluR activation was reduced by PDAc treatment. mGluR
      activation modulates glutamatergic transmission via a presynaptic autoreceptor at
      corticostriatal synapses in this newly-developed corticostriatal co-culture
      preparation as in striatal slices. Modulation of transmission occurs whether or
      not transmission involves activation of voltage-gated calcium channels.
      Furthermore, many of the characteristics of mGluR modulation of eEPSCs are shared
      by mGluR modulation of mEPSCs. These findings indicate that mechanisms downstream
      from calcium entry may contribute to modulation of synaptic transmission by mGluR
      autoreceptors.

PMID- 8532176
TI  - Presynaptic metabotropic glutamate receptors modulate omega-conotoxin-GVIA
      insensitive calcium channels in the rat medulla.
AB  - We have previously demonstrated that the metabotropic glutamate receptor (mGluR)
      agonist (1S,3R)-1 aminocyclopentane-1,3-dicarboxylate (ACPD) presynaptically
      inhibits evoked glutamatergic EPSCs and GABAergic IPSCs in patch clamped rat
      nucleus tractus solitarius (NTS) neurons recorded in this slices. The present
      study investigated the pharmacology of the presynaptic mGluRs, the the voltage
      dependent Ca2+ channel (VDCC) subtypes supporting neurotransmitter release, and
      possible interactions between the two. Monosynaptic EPSCs or IPSCs were evoked by
      electrical stimulation in the region of the tractus solitarius (TS). The effects
      of the mGluR agonists ACPD, (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG
      I) and L-2-amino-4-phosphonobutyrate (AP4) were examined upon EPSCs. The effects
      of the above compounds and quisqualate (QUIS) were examined upon IPSCs. L-CCG-I
      proved the most potent inhibitor of EPSCs and IPSCs. The VDCC blockers omega-AGA
      IVA (AGA), omega-conotoxin GVIA (GVIA), omega-conotoxin MVIIC (MVIIC) and
      nimodipine (NIM) were assessed for their ability to inhibit monosynaptic EPSCs
      and IPSCs. EPSCs were inhibited by GVIA >> AGA > or = MVIIC. IPSCs were inhibited
      by AGA > or = MVIIC >> GVIA. NIM was without effect on the EPSC or IPSC. The
      potency of mGluR inhibition of evoked synaptic transmission was assessed in the
      absence and following treatment with VDCC blockers. mGluR agonists blocked a
      greater percentage of the EPSC or IPSC following treatment with GVIA, but not the
      other VDCC antagonists, than under control conditions. We have previously
      demonstrated that the postsynaptic inhibitory effects of mGluR activation upon
      GABAA mediated currents can be mimicked by cyclic guanosine monophosphate (cGMP)
      analogs. The cGMP-dependent protein kinase (PKG) inhibitors H8 and Rp-8-4
      chlorophenylthio-guanosine-3',5'-cyclic monophosphorothioate (Rp-cG) blocked
      mGluR inhibition of GABAA mediated currents without blocking the ability of mGluR
      agonists to inhibit the IPSC. The effect of L-CCGI was enhanced following
      treatment with GVIA in the presence of Rp-cG, confirming a presynaptic locus of
      mGluR mediated inhibition of the IPSC. In contrast, cGMP analogues potentiate
      postsynaptic responses to glutamate agonists but depress the EPSC. As with the
      mGluR agonists, the inhibition of the EPSC by cGMP was potentiated following
      treatment with GVIA. These results suggest that presynaptic mGluR reduce both
      glutamate release from afferent fibers and GABA release from inhibitory
      interneurons following electrical stimulation in the region of the TS. Although
      different VDCCs support the majority of glutamate and GABA release and mGluR
      effects on release appear to utilize differing intracellular pathways,
      presynaptic GVIA-insensitive VDCCs are favorably targeted for inhibition by mGluR
      agonists.

PMID- 8532177
TI  - Pharmacology of metabotropic glutamate receptors at the mossy fiber synapses of
      the guinea pig hippocampus.
AB  - We have tested the ability of several specific agonists of glutamate metabotropic
      receptors (mGluRs) to depress synaptic transmission at mossy fiber synapses in
      the CA3 region of the guinea pig hippocampus. 1S,3R-1-amino-cyclopentyl-1,3
      dicarboxylate (ACPD) reversibly inhibited monosynaptic mossy fiber field
      potentials, presumably by a presynaptic mechanism, with an EC50 of 2.0 +/- 0.4
      microM (n = 3), suggesting the presence of mGluRs on mossy fiber synaptic
      terminals of the group 1 or 2 category. L-2-amino-4-phosphono butanoate (L-AP4)
      also inhibited responses with an EC50 of 1.1 +/- 0.2 microM suggesting that
      mGluRs of the group 3 (mGluR4, 6, 7 and 8) category of receptors are also present
      on mossy fiber terminals. Both (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L
      CCG1) and (S)-4-carboxy-3-hydroxy phenylglycine (4C3HPG) were also efficacious at
      blocking mossy fiber transmission, with an EC50 of 1.1 +/- 0.1 microM (n = 4) and
      4.8 +/- 0.6 microM (n = 3) respectively. The latter finding indicates the
      involvement of mGluRs belonging to the group 2 (mGluR2, 3) category of receptors.
      The effects of L-AP4 and L-CCG1 were both antagonized by (+)-alpha-methyl-4
      carboxyphenylglycine [(+)MCPG]. MAP4, an antagonist of group 3 mGluRs in other
      systems, blocked the effect of L-AP4, but not the effect of L-CCG1, while MCCG,
      an antagonist of group 2 mGluRs in other systems, blocked the effect of L-CCG1,
      but not the effect of L-AP4. These pharmacological findings provide strong
      evidence for the coexistence of group 2 and 3 mGluRs on the terminals of mossy
      fibers in the guinea pig.

PMID- 8532178
TI  - Pharmacological evidence for an involvement of group II and group III mGluRs in
      the presynaptic regulation of excitatory synaptic responses in the CA1 region of
      rat hippocampal slices.
AB  - The actions of four mGluR antagonists, (+)-MCPG, MAP4, MCCG and (S)-4CPG, were
      evaluated against agonist-induced depressions of synaptic transmission at the
      Schaffer collateral-commissural pathway in rat hippocampal slices. (+)-MCPG (1
      mM) reversed very effectively depressions of field EPSPs induced by (1S,3R)-ACPD
      and (1S,3S)-ACPD but had weak and variable effects on depressions induced by L
      AP4. It had no effect on depressions induced by either (-)-baclofen or carbachol.
      In contrast, MAP4 (500 microM) reversed very effectively depressions induced by L
      AP4 without affecting depressions induced by (1S,3S)-ACPD. MCCG (1 mM) had the
      opposite activity; it antagonized depressions induced by (1S,3S)-ACPD but not
      those induced by L-AP4. Finally, (S)-4CPG (1 mM) reversed small depressions of
      field EPSPs induced by high concentrations (50-100 microM) of (1S,3R)- and
      (1S,3S)-ACPD, but not L-AP4, whilst having no effect on large depressions induced
      by 10 microM (1S,3S)-ACPD in voltage-clamped cells. These results confirm and
      extend the effectiveness and selectivity of (+)-MCPG as an mGluR antagonist. The
      divergent effects of the group I antagonist, (S)-4CPG, can be explained by an
      indirect action on postsynaptic receptors which is manifest when high agonist
      concentrations are used in non-voltage-clamp experiments. The action of MCCG and
      MAP4 indicates that two pharmacologically-distinct mGluRs, belonging to classes
      II and III, can regulate synaptic transmission in the CA1 region via presynaptic
      mechanisms.

PMID- 8532179
TI  - Metabotropic glutamate receptor-induced homosynaptic long-term depression and
      depotentiation in the dentate gyrus of the rat hippocampus in vitro.
AB  - We have investigated the role of metabotropic glutamate receptors (mGluR) in the
      induction of homosynaptic long-term depression (LTD) and depotentiation (DP) in
      the dentate gyrus of the adult rat. Perfusion of the mGluR agonist (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) for a prolonged period (20
      min) induced long-term depression (LTD) of field excitatory postsynaptic field
      potentials (epsps) from the baseline level and also depotentiation (DP) from the
      long-term potentiated level. Both the ACPD-and the low frequency stimulation
      (LFS)-induced LTD and DP were inhibited in the presence of the mGluR antagonist
      (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), demonstrating the necessity for
      the activation of metabotropic glutamate receptors in the induction of LTD/DP.
      The LFS and ACPD-induced LTD were independent of the activation of N-methyl-D
      aspartate (NMDA) receptors, as they were not blocked by the NMDA receptor
      antagonist D-2-amino-5-phophonopentanoate (AP5).

PMID- 8532180
TI  - Regional and developmental profile of modulation of hippocampal synaptic
      transmission and LTP by AP4-sensitive mGluRs in vivo.
AB  - L-AP4 is an agonist at the presynaptic metabotropic receptor subtypes mGluR4,
      mGluR6 and mGluR7. In vitro, L-AP4 has been shown to reduce glutamate release and
      thereby suppress hippocampal excitatory transmission. Little data is available
      with regard to the actions of this compound in vivo. This study examined the
      effects of L-AP4 injected i.c.v. in the hippocampus of freely-moving rats on
      synaptic transmission and long-term potentiation (LTP). Two age groups were
      employed: 8-week-old and 12-week-old. Administration of L-AP4, 80 mM/5
      microliters, reduced evoked baseline responses in the dentate gyrus (DG) and CA1
      of 8-week-old rats when compared with controls. This effect was blocked by MCPG.
      L-AP4, 40 mM/5 microliters, also reduced baseline in DG but not CA1. L-AP4 (20,
      40 or 80 mM/5 microliters) had no effect on baseline in either DG or CA1 of 12
      week-old animals. However, injection of L-AP4 (80 mM/5 microliters) significantly
      reduced the amplitude of LTP induced by tetanization in CA1 and DG. This effect
      was blocked by MCPG (200 mM/5 microliters). LTP reduction, tested in 12-week-old
      animals, also occurred with an L-AP4 concentration of 40 mM/5 microliters in CA1
      but not in DG. These data indicate that L-AP4 inhibits LTP in vivo with a
      variation in sensitivity to the drug occurring between regions. It is suggested
      that the response in CA1 is produced by mGluR7, and in DG by presynaptic mGluR4
      present on perforant path neurons. These results offer in vivo physiological
      evidence for a variation in functional response and in developmental regulation
      of these subtypes, dependent on the region of the hippocampus where they are
      located.

PMID- 8532181
TI  - Pharmacological modulators of the inositol 1,4,5-trisphosphate receptor.
AB  - Elevation of cytosolic calcium concentrations, induced by many neurotransmitters,
      plays a crucial role in neuronal function. Some neurotransmitters produce the
      second messenger InsP3 which activates an intracellular calcium channel (InsP3
      receptor) usually located in the endoplasmic reticulum. This article undertakes a
      comprehensive survey of most pharmacological modulators of the InsP3 receptor so
      far reported. This review discusses in detail competitive antagonists, non
      competitive antagonists and thiol reactive reagents, highlighting their modes of
      action and in some cases indicating drawbacks in their use.

PMID- 8532182
TI  - Plasmalemmal and intracellular Ca2+ pumps as main determinants of slow Ca2+
      buffering in rat hippocampal neurones.
AB  - Using the Ca(2+)-sensitive fluorescent indicator dye fura-2, the mechanisms by
      which cytoplasmic free Ca2+ concentration, [Ca]i, decays to resting levels were
      studied in neurones cultured from the rat hippocampus. The time-course of [Ca]i
      restoration after transient elevations due to CaCl2 injections or brief exposures
      to 50 mM K Cl were biexponential. Application of specific inhibitors of systems
      participating in Ca2+ removal from cytoplasm changed both basal [Ca]i and the
      slow phase of recovery, but the fast phase was unaltered by any treatment.
      Inhibition of the plasmalemmal Ca2+ pump by external alkalinization or
      intracellular acidification was reversible, whereas calmodulin inhibitors
      (calmidazolium and triftazine, W-13) acted irreversibly. The net effects of
      blockers of the intracellular Ca2+ pump, thapsigargin (Tg) and t-BuHQ, were
      similar. Suppression of mitochondrial Ca2+ uptake or Ca2+ extrusion due to
      Na+/Ca2+ exchange, reversibly increased [Ca]i but the time-course of [Ca]i
      clearance was marginally changed. After glutamate application [Ca]i restoration
      was prolonged which was mediated by concomitant intracellular acidification
      causing inhibition of plasmalemmal Ca2+ ATPase. It is concluded that Ca2+
      homeostasis in rat hippocampal neurones is mainly determined by Ca2+ pumps in
      both the surface membrane and internal stores, whereas Na+/Ca2+ exchange and
      mitochondria play a minor role.

PMID- 8532183
TI  - (+/-)-Kavain inhibits veratridine-activated voltage-dependent Na(+)-channels in
      synaptosomes prepared from rat cerebral cortex.
AB  - Kava pyrones are pharmacologically active compounds extracted from Piper
      methysticum Forst. Because kava pyrones were characterized by their
      anticonvulsive, analgesic and centrally muscle relaxing action, we investigated
      the influence of (+/-)-kavain, a synthetic kava pyrone, on veratridine-stimulated
      increase in intrasynaptosomal Na+ concentration ([Na+]i) of rat cerebrocortical
      synaptosomes. [Na+]i was measured spectrofluorometrically employing SBFI as Na+
      sensitive fluorescence dye. Veratridine (5 mumol/I) enhanced basal [Na+]i 6.6
      fold from 11.3 to 74.1 mmol/l Na+. Incubation of synaptosomes for 100 sec with
      (+/-)-kavain was sufficient to reduce dose dependently the stimulated increase of
      [Na+]i with an IC50 value of 86.0 mumol/l, and almost complete inhibition of
      Na(+)-channels was attained with 400 mumol/l) reduced veratridine-elevated [Na+]i
      to 30.4% and 7.9% of control whereas the centrally acting muscle relaxant
      mephenesin (400 mumol/l) was without any effect. Postapplication of 400 mumol/l
      (+/-)-kavain or 10 mumol/l TTX immediately diminished veratridine-elevated [Na+]i
      to nearly basal levels with a half life time of 69.7 and 41.8 sec, respectively.
      To study the influence of (+/-)-kavain on non stimulated synaptosomes, an
      increase in [Na+]i was induced by 200 mumol/l ouabain, which enhanced [Na+]i
      hyperbolically with an initial rate of 18.4 mmol Na+/l min. Preincubation of
      synaptosomes with 400 mumol/l (+/-)-kavain or 10 mumol/l TTX partly prevented
      Na(+)-influx for both compounds to the same extent of about 57% of control. The
      presented data indicate a fast and specific inhibition of voltage-dependent Na(+)
      channels by (+/-)-kavain.

PMID- 8532184
TI  - Effects of aconitine on neurotransmitter release in the rat neuromuscular
      junction.
AB  - Aconitine (ACO), A Na+ channel activator, induces depolarization in skeletal
      muscle and blocks neuromuscular transmission. We investigated the effects of ACO
      on neurotransmitter release in the rat isolated phrenic nerve-diaphragm
      preparation at 24 +/- 1 degrees C. ACO inhibited the twitch responses to nerve
      stimulation but did not affect direct muscle contractions. ACO, without causing
      excessive membrane depolarization, increased the frequency of miniature end-plate
      potential (MEPP)s, but did not alter their amplitude or time course. The increase
      in MEPP frequency started about 60, 30 and 15 min after the application of 6, 20
      and 60 microM ACO, respectively. MEPP frequency reached its maximum (250-400 sec
      1), within 10-15 min after it began to increase. ACO, without altering direct
      muscle action potentials decreased the amplitude and blocked end-plate potential
      (EPP)s and nerve action potential (NAP)s simultaneously, before the increase in
      MEPP frequency became evident. ACO did not increase MEPP frequency in Ca(2+)-free
      media. Prior application of tetrodotoxin (1 microM) inhibited the ACO-induced
      MEPP frequency increase. Carbamazepine (120 microM) and amiloride (100 microM)
      did not completely inhibit the MEPP frequency increase but prolonged the latency.
      ACO-induced alterations in the neuromuscular transmission exhibited minimal
      recovery upon washing for 2-3 hr. These results indicate that ACO-induced
      neuromuscular blockade is mainly due to presynaptic mechanisms and can be
      explained by excessive presynaptic depolarization which leads to the blockade of
      NAPs and EPPs. Depolarization in turn increases intraterminal Ca2+ concentration
      and results in an excessive increase in MEPP frequency.

PMID- 8532185
TI  - Characterization of the effects of polyamines on the modulation of the N-methyl-D
      aspartate receptor by glycine.
AB  - We have investigated the effects of polyamine agonists and antagonists on the
      modulation of the N-methyl-D- aspartate receptor by glycine using a
      [3H]dizocilpine ([3H]MK801) binding assay. We monitored the non-equilibrium
      binding of [3H]dizocilipine in the presence of 5,7-dichlorokynurenate to preclude
      occupation of the glycine site by endogenous glycine. Using this assay, spermine
      and spermidine increased both the affinity and the maximum effect of glycine.
      Similar effects are produced by other polyamine agonists including 1,5
      diethylaminopiperidine, neomycin and Ca2+. These actions are reversed by the
      polyamine glycine produced by polyamine agonists appears to be due to an increase
      in the equilibrium affinity of [3H]dizocilpine, and cannot therefore be
      attributed solely to modulation of glycine binding. Interestingly, 1,5
      diethylaminopiperidine increases the maximum effect of glycine to a greater
      extent than it alters glycine affinity, suggesting that the two effects may be
      mediated by different sites or mechanisms. These studies will help to define the
      role of the glycine site in the modulation of the N-methyl-D-aspartate receptor
      by polyamines.

PMID- 8532186
TI  - In vitro and in vivo antagonism of AMPA receptor activation by (3S, 4aR, 6R, 8aR)
      6-[2-(1(2)H-tetrazole-5-yl) ethyl] decahydroisoquinoline-3-carboxylic acid.
AB  - The in vitro and in vivo pharmacology of a structurally novel competitive
      antagonist for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) subtype of excitatory amino acid receptors is described. LY215490, (+/-)(6
      (2-(1-H-tetrazol-5-yl)ethyl) decahydroisoquinoline-3-carboxylic acid), was shown
      to displace selectively 3H-AMPA and 3H-6-cyano-7-nitro- quinoxaline-2,3-dione (3H
      CNQX) binding to rat brain membranes. LY215490 potently antagonized quisqualate
      and AMPA-induced depolarizations of rat cortical slices in a competitive manner,
      while requiring higher concentrations to antagonize the effects of N-methyl-D
      aspartate (NMDA) and kainate. In slices of rat hippocampus, LY215490 also
      selectively antagonized AMPA-evoked release of 3H-norepinephrine. These AMPA
      receptor activities were due to the (-) isomer of the compound. (3S,4aR,6R, 8aR)
      6-[2-(1(2)H-tetrazole-5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid
      (LY293558). LY215490 was centrally active following parenteral administration in
      mice as demonstrated by protection versus maximal electroshock seizures and
      decreases in spontaneous motor activity. LY215490 (its active isomer being
      LY293558) represents a novel pharmacological agent for in vitro and in vivo
      studies of AMPA receptor function in the CNS.

PMID- 8532187
TI  - Effect of neuroactive steroids on [3H]flumazenil binding to the GABAA receptor
      complex in vitro.
AB  - Modulation of benzodiazepine receptor ligand binding to the GABAA receptor
      complex by the neuroactive steroids 3 alpha-hydroxy-dihydroprogesterone (3 alpha
      OH-DHP) and 3 alpha-hydroxycorticosterone (3 alpha- THDOC) was assessed in an in
      vitro binding assay with the benzodiazepine antagonist [3H]flumazenil using rat
      cortical membranes. Neuroactive steroids, pentobarbital, GABA and bicuculline did
      not significantly affect flumazenil binding. However, the addition of neuroactive
      steroids significantly decreased the Ki of benzodiazepine agonists, including
      alprazolam, diazepam and clonazepam, indicating an increase in agonist affinity.
      Only the addition of 3 beta-OH-DHP, an inactive stereoisomer had no effect on the
      Ki of these agonists. The binding of the benzodiazepine inverse agonist FG 7142
      was not significantly affected by these steroids, but the addition of GABA
      significantly increased the Ki of FG 7142 indicating a decrease in inverse
      agonist affinity. High concentrations of GABA or bicuculline were able to occlude
      the 3 alpha-THDOC mediated decrease in alprasolam Ki, indicating a GABA dependent
      mechanism of binding enhancement. An advantage of using [3H]flumazenil is that
      neither the Ki nor the Bmax change in the presence of allosteric site modulators,
      permitting the simple and direct assessment of alterations in benzodiazepine
      ligand affinity for the GABAA receptor complex by neuroactive steroids.

PMID- 8532188
TI  - Autoradiographical study of types 1 and 2 of benzodiazepine receptors in rat
      brain after chronic ethanol treatment and its withdrawal.
AB  - The effect of chronic ethanol treatment, and its withdrawal on benzodiazepine
      binding sites in rat brain is described in this autoradiographical study using
      the benzodiazepine agonist [3H]flunitrazepam. Several areas of the rat cerebral
      cortex, hippocampus, mesencephalon, cerebellum and lateral geniculate nucleus
      were studied in animals, chronically treated with ethanol, and 24 or 48 hr after
      ethanol withdrawal. The [3H]flunitrazepam binding and the relative percentages of
      binding to BZ1 and BZ2 sites, using zolpidem as a BZ1 site inhibitor, are
      described. The cerebellum and red nucleus, which only express BZ1 binding sites,
      appear to be areas significantly modified by ethanol and its withdrawal. In no
      other structure did ethanol modify [3H]flunitrazepam binding nor change the
      relative percentage of BZ1 and BZ2 sites.

PMID- 8532189
TI  - Immediate early gene expression during morphine withdrawal.
AB  - The expression of immediate early genes (IEG)s c-fos, c-jun and zif/268 was
      studied during naloxone-precipitated morphine withdrawal in various organs of the
      rat. Dependence was induced over a period of 6 days by a graded regimen of 6
      hourly injections. Northern analysis revealed peak expression of all IEGs
      occurred in the forebrain plus cerebellum at 20 min and at 60 min in the brain
      stem following morphine withdrawal. Increased levels of c-fos and c-jun mRNA were
      observed in the spinal cord at 40 min of morphine withdrawal. An increase in c
      fos and c-jun but not zif/268 mRNAs was seen in the jejunum between 20 and 60
      min. Elevated levels of the IEG protein products in the cerebral cortex,
      hippocampus, thalamus, cerebellum, brain stem and spinal cord were observed at 60
      min following morphine withdrawal. These data emphasize the temporal and spatial
      variation in IEG expression in different tissues during opiate withdrawal.

PMID- 8532190
TI  - Release of acetylcholinesterase from guinea-pig substantia nigra: effects of
      tryptaminergic drugs and dorsal raphe nucleus stimulation.
AB  - The guinea-pig substantia nigra receives a 5-hydroxytryptaminergic (5-HT ergic)
      projection from the dorsal raphe nucleus. In this study we have attempted to
      identify the 5-HT receptor subtype mediating release of acetylcholinesterase
      (AChE) from nigral neurones, measured by assay of perfusate obtained via
      chronically implanted push-pull cannulae. The effects of direct nigral
      application of 5-HT, 2-methyl-5-HT and 5-methoxytryptamine. Application of
      submicromolar concentrations of 5-HT, 2,5,-dimethoxy-4- iodoamphetamine and alpha
      methyl-5-HT significantly enhanced release of AChE, whereas 5
      carboxamidotryptamine, sumatriptan, 2-methyl-5-HT and 5-methoxytryptamine were
      ineffective at a similar concentration range. Electrical stimulation (50 Hz, 20
      300 mu A) of the dorsal raphe nucleus evoked release of AChE from the substantia
      nigra, and induced a rotational behavioural effect for the duration of
      stimulation. Pretreatment with 5,7,-dihydroxytryptamine inhibited both DRN-evoked
      release of AChE and animal rotation. The 5-HT receptor antagonists ketanserin and
      ritanserin (10(-7)-10(-6)M, when applied to the substantia nigra, inhibited raphe
      stimulated AChE release. Drugs which inhibited raphe-stimulated release of AChE
      had no effect on concomitant animal rotation, indicating that the behavioural
      events are mediated via distinct processes, unrelated to those mediating nigral
      AChE release. The data suggest that evoked release of AChE from the substantia
      nigra by stimulation of the dorsal raphe nucleus may be mediated in part via a 5
      HT2 receptor type. The 5-HT1D agonists 5-carboxamidotryptamine (10(-6)M and
      sumatriptan (10(-5)M also inhibited raphe-evoked AChE release, suggesting a
      possible presynaptic autoinhibitory role for 5-HT1D receptors on raphe-nigral
      nerve terminals.

PMID- 8532191
TI  - Glucocorticoid receptor-mediated inhibition by corticosterone of 5-HT1A
      autoreceptor functioning in the rat dorsal raphe nucleus.
AB  - In the rat brain, the dorsal raphe nucleus contains a large proportion of
      serotoninergic neurons, which are mostly regulated by somato-dendritic 5-HT1A
      autoreceptors. This nucleus also possesses intracellular glucocorticoid receptors
      (GR), which may be involved in the well established modulation of serotonin (5
      hydroxytryptamine, 5-HT) metabolism by glucocorticoids. Control by
      corticosteroids of 5-HT1A receptor-mediated inhibitory control of the firing of
      serotoninergic neurons in the dorsal raphe nucleus was investigated using an in
      vitro electrophysiological approach. The spontaneous firing rate of
      serotoninergic neurons recorded in brain stem slices and its inhibition due to 5
      HT1A autoreceptor stimulation by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH
      DPAT) were similar in adrenalectomized rats and sham-operated animals. In vitro
      pretreatment with corticosterone (30-100 nM) significantly reduced 8-OH-DPAT
      induced inhibition of the 5-HT cell discharge in slices from adrenalectomized
      rats. This effect could be prevented by the GR antagonist, 11 beta-(4-dimethyl
      amino-phenyl)- 17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one (RU)
      38486, 30 nM), and mimicked by the GR agonist, 11 beta, 17 beta-dihydroxy-6
      methyl-17 alpha (prop-1-ynyl) androsta-1,4,6-trien-3-one (RU 28362, 500 nM). In
      contrast, the mineralocorticoid receptor (MR) agonist, aldosterone (10 nM), did
      not alter 8-OH-DPAT-induced inhibition in tissues from adrenalectomized animals.
      Complementary autoradiographic experiments showed that [3H]8-OH-DPAT specific
      binding to 5-HT1A sites in the dorsal raphe nucleus (and the hippocampus) was not
      significantly altered following adrenalectomy and exposure of brain stem slices
      to corticosterone. These data suggest that GR are involved in the suppressive
      effects of high levels of corticosterone on the 5-HT1A receptor-dependent
      regulation of 5-HT neuronal activity in the rat dorsal raphe nucleus.

PMID- 8532192
TI  - The role of hippocampal 5-hydroxytryptamine 1A (5-HT1A) receptors in the
      anticonflict activity of beta-adrenoceptor antagonists.
AB  - The nonselective beta-adrenoceptor antagonists pindolol and cyanopindolol, which
      bind to 5-HT1A and 5-HT1A receptors showed an anticonflict effect by increasing
      the number of punished licks in the Vogel conflict test in rats, when
      administered directly into the CA, region of the dorsal hippocampus (i.hp.). The
      maximum effect was observed after intrusion of 1 microgram of pindolol and 3
      microgram of cyanopindolol. However, the selective beta 1-and beta2-adrenoceptor
      antagonists betaxolol and ICI 118,551, respectively, which have a negligible
      affinity for 5-HT receptors, did not affect the punished responding, when
      administered i.hp. in doses up to 10 micrograms. The anticonflict effect of
      pindolol (1 microgram) was significantly reduced by (S)-WAY 100135, a selective 5
      HT1A-receptor antagonist, administered i.hp (0.1 microgram) or s.c. (10 mg/kg).
      Furthermore, (S)-WAY 100135 injected i.hp (0.3 micrograms) significantly
      antagonized the anticonflict effect of pindolol injected i.p. (8 mg/kg). (S)-WAY
      100135 given alone i.hp. (0.03-3 micrograms) or s.c. (5-10 mg/kg) did not affect
      the punished responding in rats. These results indicate that the anticonflict
      effect of the beta-blockers which were tested, or at least pindolol, depends on
      their agonist action on postsynaptic 5-HT1A receptors located in the hippocampus.

PMID- 8532193
TI  - [Laparoscopic treatment of acute cholecystitis. Personal experience and
      preliminary results].
AB  - At the beginning of their experience the authors limited laparoscopic treatment
      to simple cholelithiasis. They then extended this method to acute cholecystitis.
      They report here 11 cases with no mortality and morbidity and a conversion rate
      equal to 18.18% (2 cases of new acute phase of chronic cholecystitis after
      deferred emergency surgical treatment). The postoperative stay in hospital never
      exceeded 72 hours for the 9 cases of laparoscopic cholecystectomy, while the 2
      cases of laparotomic respectively on the VII and VIII days. In consideration of
      what is reported in the literature and of personal experience, even if limited,
      the authors acknowledge that laparoscopic cholecystectomy if it is practised by
      an expert surgeon in the presence of precise indications and with a low
      conversion rate.

PMID- 8532194
TI  - [Cholecystectomy with laparoscopy and laparotomy. Analysis of the complications].
AB  - Laparoscopic cholecystectomy (LC) has been adopted by many as the treatment of
      choice for uncomplicated biliary lithiasis; since an increasing number of
      surgeons use LC even in complicated cases, we examined our series in order to see
      if this is the correct procedure. We report on the results of our first 252 LC
      and compare them with our latest 66 open cholecystectomies, in order to evaluate
      number and importance of postoperative complications. Besides we compare
      complications in patients below and over 60 years of age to verify if age bears
      any significance. We found no difference in frequency of complications among
      patients younger or older than 60; highly significant is, on the contrary, the
      difference in complications between the two procedures, the incidence being much
      lower in the laparoscopic one. We state that LC is a safe and effective procedure
      and suggest it as the method of choice for the treatment of any symptomatic
      gallbladder stone disease.

PMID- 8532195
TI  - [Intraoperative cholangiography in laparoscopic cholecystectomy. Our experience].
AB  - Cholangiography during conventional cholecystectomy has always been useful for
      anatomo-topographic study and for research of the stones of biliary tree. After a
      natural period of training the authors included the easy technique of
      cholangiography in laparoscopic cholecystectomy. The study was performed in 13
      patients using Olsen's cannula with an internal a normal catheter for
      cholangiography. The catheterization of the cystic duct was performed in 85% of
      cases (11 patients), in the other 15% (2 patients) it was not possible to
      cannulate the cystic duct. Non complication. The mean duration of the study was
      14 minutes. The authors describe the technique and conclude, after a brief
      discussion of the reports in the literature and personal experience, that
      peroperative cholangiography is an easy and safe procedure without risk and
      prevents the injuries to the biliary tract whose incidence is about 1.3%.

PMID- 8532196
TI  - [Primary gastric lymphoma. 14 clinical cases].
AB  - Fourteen patients affected by primary gastric lymphoma were observed
      retrospectively to verify the results of surgical and adjuvant chemotherapy.
      After a 85% preoperative diagnostic specificity, 79% of patients were subjected
      to surgical therapy by subtotal gastrectomy (93%) and by total gastrectomy (7%),
      and 64% of patients were subjected to adjuvant chemotherapy in conformity with
      CHOP and CVP. Classified by the Working formulation, 57% of cases presented a
      high grade of malignancy, 29% a low grade and 14% an intermediate grade.
      Classified by Ann Arbor with Mushoff's modification, 43% of patients were
      assigned to stage IIE1, 36% to stage IE, 14% to stage IIE2 and 7% to stage IIIE.
      Operative mortality was null. The overall median survival have been of 21 months,
      while surgical and chemotherapeutical median survival reached 32 months. The 5
      year actuarial survival was: 10% (overall), 14% (treated patients), 50% (low
      grade), 33% (stage IE). With negative influence by istology and staging.

PMID- 8532197
TI  - [Bronchial carcinoid tumors. Retrospective analysis of 32 cases].
AB  - Thirty-two cases of bronchial carcinoids (rate m/f = 1, average age 50.33 years)
      had been treated from 1970 to 1993. 62.5% of patients were symptomatic, 6% with
      specific symptoms. 62.5% of tumors had a central growth. Thirty-one patients
      underwent surgical treatment, another one a laser Nd:YAG coagulation. The
      operative mortality and morbidity were respectively 3% and 0%. 84.4% of tumours
      were typical carcinoid, 11% of those had lymphonodal metastases. Atypical
      carcinoids were found in 15.6% of patients, 40% had lymphnodal metastases. The
      global actuarial survival to 1, 5, 10 years were respectively 96, 88 and 84%.
      Statistically the survival difference between the typical and atypical carcinoid
      is relevant. The authors underline the preoperative cytologic diagnosis to
      perform a minimal lung resection in typical bronchial carcinoids.

PMID- 8532198
TI  - [Quality of life after pulmonary resection for bronchogenic carcinoma. Evaluation
      of a group of patients surviving more than five years].
AB  - The method of guided-interview on selected questionnaires was employed for the
      assessment of quality of life in patients radically resected for lung cancer. A
      selection of thirty patients was done in a group of 151 long-term survivors non
      treated by adjuvant therapy. An assessment protocol and personal results were
      discussed.

PMID- 8532199
TI  - [A novel diagnostic method to study the residual pelvic cavity after Miles
      abdomino-pelvic resection].
AB  - Local pelvic perineal recurrence represents the most frequent site of failure
      following abdominoperineal resection (APR) for rectal cancer. Patients con be
      studied at this level by Computerized Tomography (CT) scan, Magnetic Resonance
      Imaging (MRI), suprapubic or, in women, endovaginal ultrasound (US). CT scan and
      MRI show sensitivity and specificity in excess, respectively, of 70 and 90%, but
      the high cost and the invasiveness of CT scan controindicate their frequent use.
      Suprapubic US has no value in terms of diagnostic accuracy, whereas endovaginal
      US shows a good specificity, but it is quite refused by the patients since the
      discomfort of the examination. 34 patients from the Rehabilitation Unit of
      Colostomy Patients at the University of Rome, "La Sapienza", have been blindly
      followed by transperineal US. The results have been compared with those obtained
      by CT scan or MRI. Specimens have been obtained of any suspicious mass by needle
      biopsy. The diagnostic accuracy of transperineal US has resulted comparable to CT
      scan and MRI. The authors also describe the morphology and US pattern of the
      pelvic hollow as demonstrated by transperineal US and the distinctive features of
      abnormality seen.

PMID- 8532200
TI  - [Current trends in the treatment of Graves' disease].
AB  - Between 1973 and 1992 153 patients with Graves' disease were observed at the
      Surgery and Oncology Institute-Cagliari University. 103 underwent subtotal (70)
      or total (33) thyroidectomy, while 50(after 1985) were submitted to radioactive
      iodine therapy. Surgical indications were failure of antithyroid drug therapy,
      signs of compression and large size goitre. Until 1988, all patients were
      submitted to subtotal thyroidectomy with thyroid remnant of about 8 g. From 1988
      the choice of total thyroidectomy came out from: similar complications (paralysis
      of recurrent nerve and hypoparathyroidism), lack of relapse and suppression of
      risk of occult carcinoma. After subtotal thyroidectomy definitive
      hypoparathyroidism in 1 patient (1.8%), transitory hypoparathyroidism in 5
      (9.4%), clinical hypothyroidism in 17 (31.5%), recidive hyperthyroidism in 3
      patients (5.5%) were observed. After total thyroidectomy 1 patient presented
      definitive paralysis of recurrent nerve (3%), 1 definitive hypoparathyroidism
      (3%), 8 transitory hypoparathyroidism (24%): small (44 patients) or large goitre
      (3 patients) or relapse (3 patients) were indications to radioactive-iodine
      therapy. At median follow-up of 16 months no relapses of hyperthyroidism were
      observed, while clinical signs of hypothyroidism were present in 33% of patients.
      Authors stress that, after a first attempt with antithyroid drugs therapy,
      radioiodine treatment is elective in Graves' disease. Surgery still remains the
      treatment of choice during pregnancy, in patients with large goitres, signs of
      compression or in presence of scintigraphic "cold" area.

PMID- 8532201
TI  - [Lateral cysts and fistulas of the neck. Diagnosis and treatment].
AB  - Lateral neck cysts and fistulae are considered to be a well-defined clinical
      entity which needs a precise knowledge of the development of the branchial system
      to have an appropriate and subsequent successful treatment. According to the
      recent classification cysts of I and II type and fistulae of I, II and III type
      can be recognized. In the former ultrasonography and Computerized Tomography
      represent the most appropriate diagnostic tools, while in the latter
      fistulography is preferred. An elective surgical excision seem to be resolutive
      in the majority of cases: on the contrary emergency surgery is related to a
      certain relapse of this pathology. 45 cases of branchial pathology are reported;
      diagnostic and therapeutic choices are then discussed.

PMID- 8532202
TI  - [The role of transplanted vein graft in arterial reconstruction].
AB  - The use of the non-reversed saphenous vein has not been properly evaluated yet,
      for what concerns the features of length and application. In the reported series
      this technique has been employed for the reconstruction of arterial segments in
      various anatomic sites. The mean follow-up was 10 months. Between November 1987
      and September 1993 at the Department of Vascular Surgery of Pietra Ligure and
      Imperia 39 arterial grafts with the use of non-reversed autologous saphenous vein
      were performed, for the treatment of arteriosclerotic, traumatic or aneurysmatic
      diseases. On the basis of the outcomes (70 to 100% patency of the grafts found at
      the follow-up), pro and cons of this technique is weighed up and some guidelines
      about the procedure of choice (among the non-reversed, in situ or reversed
      saphenous vein) are settled, keeping in mind the different variations who must
      influence and direct the surgeons' choice (venous diameter, features of the site
      to revascularize etc.).

PMID- 8532203
TI  - [Ambulatory phlebectomy with Muller procedure in the treatment of lower limb
      varices. Indications, technique and long-term results].
AB  - The authors report the results of more than five years experience of
      phlebectomies, according to Muller's method, performed both in general anesthesia
      during stripping operations and in local practice. The results confirmed the
      validity of this complementary surgical treatment for its radicality, execution
      simpleness and best respect for aesthetics.

PMID- 8532204
TI  - [Clinical value of spleen autograft].
AB  - A relaparotomy for cholecystectomy in a 21 year old patient, who received a
      spleen autograft after a traumatic injury four years before, allowed us to
      describe the long term morphological and functional follow-up of the
      autotransplanted spleen, with a histological evaluation of one of the grafts. We
      point out the technical aspects of the surgical procedure with a review of the
      experimental background. We underline the analogy of the functional features of
      the splenic autograft both in the experimental field and in the clinical setting.
      The histological study of the splenic fragment in our case showed the same
      structural pattern of the experimental studies. Thus we stress the hypothesis of
      an effective protection of the implanted splenic tissue against the overwhelming
      post-splenectomy sepsis in man.

PMID- 8532205
TI  - [A case of gastric hemangiopericytoma].
AB  - The authors report a case of gastric hemangiopericytoma. This tumor,
      histogenetically derived from pericytes, has been detected in any tissue or
      structure. According to the review of the literature, the hemangiopericytoma of
      the stomach occurred very uncommonly, being published only 29 cases. Diagnosis is
      based on histological and immunohistochemical techniques. Surgery is the main
      therapy but the impredictable biological behaviour require different strategies.

PMID- 8532206
TI  - [Gastric leiomyoblastoma. Two case reports].
AB  - Two cases of gastric leiomyoblastoma (one of which of exceptional size, measuring
      more than 40 cm) observed respectively in 1992 at the Surgery Division of USSL 45
      at Asola (MN) and in 1990 at the Second Surgery Division of USSL 47 in Mantova
      are reported. In the first case anaemia revealed the tumor whereas in the second
      case the patient suffering from a pain in the abdomen was admitted to hospital.
      These two tumors raise interest for their rarity and for their uncertain
      biological evolution. They generally develop very slowly and tend to remain
      intramural. The most frequently attacked seats are the antum-pyloric region and
      the stomach body. The main symptoms are epigastric pain, nausea, vomiting, weight
      loss, sideropenic anaemia, epigastric palpable mass. The diagnostic iter includes
      radiologic examination (digestive tube X-ray, echography, TAC, arteriography),
      gastroscopy and laparoscopy. In most cases surgical resection is not completely
      destroying, except for those cases in which the tumor measures more than 5 cm and
      total or subtotal gastrectomy is performed.

PMID- 8532207
TI  - [Angiodysplasia of the right colon].
AB  - Ascending colon angiodysplasia is a frequent cause of colorrhagia or chronic
      blood loss in old patients, but also possible under the age of 55. Angiodysplasia
      diagnosis is often underestimated. For a long time colorrhagia or lower
      intestinal bleeding were generally diagnosed like diverticular bleeding. This
      conclusion was the result of several conditions: the conservative management of
      distal gastrointestinal bleeding is in most cases successful; the double dye
      clysma was the first and the main diagnostic procedure for many years and the
      result was a not correct diagnosis of diverticular bleeding since large bowel
      diverticulosis is always present in the elderly. The authors report on three
      cases of low intestinal bleeding where the diagnosis of angiodysplasia in the
      first patient was performed by upper mesenteric artery arteriography, in the
      second by preoperative colonoscopy and after confirmed by the histology of the
      specimen and in the last one by colonoscopy performed in emergency and after
      intestinal irrigation. The first patients refused the operation; the second had
      right hemicolectomy and the third one had a spontaneous stop of bleeding.
      According to their clinical experience the authors suggest that colonoscopy
      performed in emergency or intraoperative is the first choice diagnostic
      procedure: it can detect the source of bleeding between right or left colon.
      Arteriography often shows vascular images characteristic for angiodysplasia or
      other vascular malformations but, in our experience, it may be absolutely not
      diagnostic. Colonoscopy performed in emergency during bleeding or per-operative
      is the best procedure in order to diagnose the source of bleeding. Emergency
      colonoscopy can distinguish if the blood is coming from the right or left colon
      and in our experience, colonoscopy during bleeding is always possible because
      blood has a cathartic effect. In case of emergency operation pre-operative
      colonoscopy can usually detect the source of bleeding. A double dye clysma,
      whether barium or hydrosoluble doesn't give a diagnostic support in low
      intestinal bleeding; on the contrary it can prevent a correct arteriographic and
      endoscopic evaluation. At last histopathological findings on the specimen are
      conclusive for the diagnosis.

PMID- 8532208
TI  - [Biliary ileus. Case report and therapeutic considerations].
AB  - The authors, after having described, a case of biliary ileus, analyse the
      principal pathogenetic aspects of the disease, and underline the diagnostic and
      therapeutic difficulties. They believe that the simple enterolithotomy
      represents, initially, the best therapy, in particular with patients in poor
      clinical conditions.

PMID- 8532209
TI  - [Localized dissection of the abdominal aorta. Diagnosis and surgical treatment].
AB  - Abdominal aortic dissection is a rare pathology. As far as we are concerned, only
      59 cases have been reported in the English literature. In the last two years, two
      cases were treated at our Institution. Both were males, over 70 years of age.
      They were evaluated with ultrasonography, angiography (1 case) and Magnetic
      Resonance Imaging which showed localised dissection of the abdominal aorta with
      aneurysmal dilatation. They underwent surgical treatment with good results. At 1
      and 2 years from operation both patients are alive and well. A postoperative
      ultrasonography didn't show any residual dissection.

PMID- 8532210
TI  - [Granular cell tumor of the male breast. Case report and review of the
      literature].
AB  - The authors report a case of granular cell tumor of the breast arising in a 38
      year old man. Preoperative diagnosis was of breast carcinoma. However, frozen
      sections showed the benign nature of the tumour. It is important to identify this
      lesion as, in spite of a clinical and mammographic similarity with carcinoma, its
      behaviour is quite benign, and a simple tumour excision is the recommended
      treatment.

PMID- 8532211
TI  - Molecular biology of the opioid receptors: structures, functions and
      distributions.
AB  - Opiates like morphine and endogenous opioid peptides exert their pharmacological
      and physiological effects through binding to their endogenous receptors, opioid
      receptors. The opioid receptors are classified into at least three types, mu-,
      delta- and kappa-types. Recently, cDNAs of the opioid receptors have been cloned
      and have greatly advanced our understanding of their structure, function and
      expression. This review focuses on the recent advances in the studies on opioid
      receptors using the cloned cDNAs. We describe the molecular cloning of the opioid
      receptor gene family and studies of the structure-function relationships, modes
      of coupling to second messenger systems, pharmacological effects of antisense
      oligonucleotide and anatomical distributions of opioid receptors.

PMID- 8532212
TI  - L-DOPA systems for blood pressure regulation in the lower brainstem.
AB  - We have explored probable neurotransmitter roles of L-3,4-dihydroxyphenylalanine
      (L-DOPA) in baroreceptor reflex and blood pressure regulation in depressor sites
      of the nucleus tractus solitarii (NTS) and the caudal ventrolateral medulla
      (CVLM), and in pressor sites of the rostral ventrolateral medulla (RVLM) in
      anesthetized rats. During microdialysis of these three areas, the basal L-DOPA
      release is in part tetrodotoxin (TTX)-sensitive and Ca2(+)-dependent, high K+
      Ca2(+)-dependently releases dL-DOPA. L-DOPA microinjected (10-300 ng) dose
      dependently produces postsynaptic depressor responses in the NTS and CVLM and
      pressor responses in the RVLM, and a recognition site for L-DOPA functions
      tonically to activate depressor neurons in the NTS and CVLM and pressor neurons
      in the RVLM. It is highly probable that L-DOPA is a neurotransmitter of the
      baroreceptor afferents terminating in the NTS, which is based on further findings
      such as (1) antagonism by a competitive L-DOPA antagonist against depressor
      responses to aortic nerve stimulation, (2) TTX-sensitive L-DOPA release by aortic
      nerve stimulation, (3) abolition of baroreceptor-stimulated L-DOPA release by
      bilateral sino-aortic denervation and (4) decreases in tyrosine hydroxylase (TH)-
      and L-DOPA-immunoreactivities without modifications of dopamine- and DBH
      immunoreactivities in the left NTS and ganglion nodosum 7 days after ipsilateral
      aortic nerve denervation peripheral to the ganglion. In the NTS, GABA tonically
      functions to inhibit via GABAA receptors L-DOPA release and depressor responses
      to L-DOPA, whereas L-DOPA induces GABA release. Impaired TTX-sensitive neuronal
      activity to release L-DOPA in the NTS and enhanced TTX-sensitive neuronal
      activity including a decrease in decarboxylation of L-DOPA to dopamine and an
      increase in sensitivity of the recognition site to L-DOPA in the RVLM are
      relevant to the maintenance of hypertension in spontaneously hypertensive rats.
      Decreases in the contents of L-DOPA in the right CVLM 10 days after electrical
      lesion of the ipsilateral NTS suggest a 'L-DOPAergic' and monosynaptic relay from
      the NTS to the CVLM. L-DOPA seems to play major roles as a neurotransmitter for
      baroreceptor reflex and blood pressure regulation in the lower brainstem of rats.

PMID- 8532213
TI  - Long-lasting facilitation and depression of periurethral skeletal muscle
      following acupuncture-like stimulation in anesthetized rats.
AB  - The effects of acupuncture-like stimulation on the tone of the partially filled
      bladder and on the periurethral electromyogram (EMG) were examined in urethane
      anesthetized rats. Acupuncture-like stimuli were usually applied to the skin and
      underlying muscles (or other structures), either separately or together, for a
      period of 1 min; the effects were studied in spinal cord intact and in spinalized
      animals. Maps have been constructed showing the effects of acupuncture-like
      stimulation at different sites on the body surface and of similar stimulation
      applied to individual muscles, the urethra and the testis. When acupuncture-like
      stimuli were applied to the skin and underlying structures, in the rostral half
      of the body and the hindpaw, testis or urethra, these stimuli usually induced
      excitation of periurethral EMG activity. Depression of EMG activity was seen
      predominantly during stimulation of structures close to the urethra, but not
      opposed to it. When acupuncture-like stimuli were applied only to structure
      beneath the skin, depression of EMG activity usually occurred. Acupuncture-like
      stimulation of the bulbocavernosus, which partly overlies the proximal urethra
      produced depression of EMG activity in 50% of trials, but the incidence of
      similar effects from the more distant pubococcygeus, or the dorsal or ventral
      sacrococcygeal muscles was about 90-100%. Acupuncture-like stimulation for 1 min
      could produce either excitation or depression of periurethral EMG activity
      lasting about 5 or 6 min, depending on the site of insertion and rotation of the
      acupuncture needles. Excitation of short duration (less than 3 min) was
      consistently observed from areas of the body distant to the bladder, i.e. the
      nose, forepaw, forelimb, chest, abdominal wall and hindpaw. Longer lasting
      excitation of EMG activity was often seen from the penile urethra, perineal area
      and hindlimb. Depression of EMG activity with a duration of more than 3 min was
      consistently seen from the muscles at the base of the tail (sacrococcygeus) and
      perineal area (pubococcygeus and bulbocavernosus). The bladder was partially
      filled in these experiments, so that micturition contractions were never seen;
      acupuncture-like stimulation of the perineal area induced some increase in
      bladder tone in 40% of trials. In spinalized animals, the pattern of activity
      induced by acupuncture-like stimulation was similar to that seen in spinal cord
      intact animals and the durations of the effects were not significantly different
      in these two groups. The distribution of sites from which acupuncture-like
      stimuli can influence the activity of the lower urinary tract is discussed.

PMID- 8532214
TI  - Activation of peripheral and/or central chemoreceptors changes retching
      activities of Botzinger complex neurons and induces expulsion in decerebrate
      dogs.
AB  - Fictive expulsion can be induced by electrical stimulation of the carotid sinus
      nerve during fictive retching or by discontinuing artificial ventilation in
      decerebrate paralyzed dogs. Both the phrenic and abdominal muscle nerves
      discharge during the early phase of fictive expulsion, but only the abdominal
      muscle nerve continues to discharge during the late phase. To determine whether
      Botzinger complex (BOT) neurons participate in expulsion, responses to sinus
      nerve stimulation were examined in 47 non-respiratory (N-RES), 15 inspiratory
      (INS) and 12 expiratory (EXP) BOT neurons during eupnea. About 80% of the neurons
      produced excitatory or inhibitory responses. FIring patterns were observed in 61
      N-RES, 39 INS and 56 EXP BOT neurons during expulsion induced by sinus nerve
      stimulation or by discontinuation of artificial ventilation. An activity pattern
      similar to that of the phrenic nerve was exhibited during fictive retching and
      expulsions by 13 N-RES< 3 INS and 8 EXP neurons, and a firing pattern like that
      of the abdominal muscle nerve was produced by 11 N-RES, 6 INS and 5 EXP neurons.
      Bursts were limited to the late phase of expulsion and to the period just after
      expulsion in 5 N-RES, 3 INS and 3 EXP neurons, and in 8 N-RES and 21 EXP neurons,
      respectively. Firings of the two latter groups of neurons decreased concomitantly
      with each retch or during retching. These results suggest that neurons of the two
      latter groups play crucial roles in the central patterning of neuronal expulsion
      activities.

PMID- 8532215
TI  - Vascular permeability to growth hormone in the rat central nervous system after
      focal spinal cord injury. Influence of a new anti-oxidant H 290/51 and age.
AB  - Vascular permeability to the growth hormone (GH) across the blood-brain barrier
      (BBB) is unknown. This investigation was undertaken to examine vascular
      permeability to 125I-labelled rat growth hormone (rGH) in the central nervous
      system (CNS) of normal animals. Since age and spinal cord injury influences the
      metabolism of GH, these factors were also included. No statistically significant
      difference was seen regarding rGH permeability between young (aged 19-21 weeks)
      and old (age 38-42 weeks) animals. A focal trauma to the cord, produced by an
      incision into the right dorsal horn of the T10-11 segments in young animals,
      increased rGH permeability in several spinal cord segments at 0.5-5.0 h after
      injury. This permeability increase progressed over time. Similar trauma to old
      rats resulted in a significantly less increase in rGH permeability in the spinal
      cord 5 h after the trauma. This indicates that trauma-induced increased
      permeability of rGH is age-dependent. Pretreatment of normal young animals with a
      new antioxidant (H 290/51) did not influence the rGH permeability. However the
      drug prevented the trauma-induced increase of rGH permeability at 5 h after
      injury. This indicates that inhibition of lipid peroxidation has some protective
      effect on trauma-induced increase in rGH permeability.

PMID- 8532216
TI  - The influence of afferent inputs from skin and viscera on the activity of the
      bladder and the skeletal muscle surrounding the urethra in the rat.
AB  - (1) Somato-visceral and viscero-visceral reflex interactions have been studied in
      the bladder branches of the pelvic nerve and in the electromyographic (EMG)
      activity of the periurethral skeletal muscles of the anesthetized rat, and by
      observations of changes in bladder motility. (2) Slow distensions of the bladder
      caused some elevation of intravesical pressure, and culminated in a micturition
      contraction. Periurethral EMG activity increased gradually during the bladder
      distension, and showed an oscillatory marked increase during the bladder
      contraction. There was a small increase in pelvic nerve efferent activity during
      slow distension, and there was a substantial increase before, or at the start, of
      a micturition contraction. (3) Oscillatory bursting activity occurred in
      recordings of the EMG activity from periurethral skeletal muscle during the
      rising phase of micturition contraction; this was particularly so during the most
      rapid rise in intravesical pressure, and periods of electrical silence lasting 80
      270 ms alternated with bursts of activity in the periurethral EMG. (4) In the
      present experiments, the switching mechanism activated by pelvic afferent signals
      related to intravesical pressure reversed the behavior of a number of reflex
      pathways. When the bladder pressure was low, nociceptive pinching of the perineal
      skin usually caused bladder contraction and a rise in pelvic nerve efferent
      activity and in periurethral EMG activity. When the bladder was full, micturition
      contractions were present and reduced in size and frequency by pinching of the
      perineal skin. The pelvic nerve efferent activity was correspondingly reduced,
      while the EMG activity increased during and following the nociceptive stimulus.
      Cooling the scrotal skin with ice also decreased the frequency of bladder
      contractions. (5) When the bladder pressure was low, distension of the anus and
      colon increased periurethral EMG activity, but did not affect bladder tone.
      However, when the bladder was full, these stimuli reduced the size and frequency
      of bladder contractions, associated with a reduction in the pelvic nerve efferent
      activity. There was usually a simultaneous reduction in the EMG activity in
      periurethral muscles. Similar results were obtained during distension of the
      seminal vesicles or vagina, or following injection of 20-60 microliters of saline
      into the lumen of the vas deferens. Reversal of the responses at extremes of
      intravesical pressure was observed in every case. (6) Following spinal
      transection at the upper cervical or thoracic level, micturition contractions
      were absent at high bladder volumes. However the effects described when the
      neuraxis was intact and the bladder pressure was low were still
      observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8532217
TI  - The role of the gamma-system for improving information transmission in
      populations of Ia afferents.
AB  - Ensemble coding of simple mechanical stimuli (small sinusoidal stretches) was
      studied in populations of simultaneously recorded primary muscle spindle
      afferents (MSAs). The experiments were made on 39 primary MSAs in chloralose
      anaesthetised cats. For the analyses we used a combination of principal component
      analysis and algorithms for quantification of stimulus discrimination. Ensembles
      of primary MSAs discriminated better between different muscle stretches than
      individuals, and showed a successive increase in discriminative ability with
      increasing ensemble size. The ensemble effect disappeared after cutting the
      ventral roots, indicating an important role for the fusimotor system in ensemble
      coding. Simultaneously recorded ensembles of MSAs showed significantly better
      discriminative ability than pooled sequentially recorded MSAs. This difference
      was abolished by the cutting of the ventral roots. It is hypothesised that, since
      the muscle spindles are connected to each other via secondary MSAs (projecting to
      gamma-motoneurones to other spindles), the fusimotor-muscle spindle system may
      constitute a neural network, in which each 'neuron' (i.e., each individual muscle
      spindle) is influenced by the activity in the whole network. In populations of
      pooled sequentially recorded MSAs, the connections would not exist. Thus, the
      population would lose its neural network quality, and the encoding ability of the
      population would decrease.

PMID- 8532218
TI  - Reaction of microglial cells and macrophages after cortical incision in rats:
      effect of a synthesized free radical scavenger, (+/-)-N,N'
      propylenedinicotinamide (AVS)
AB  - Reactive microglial cells and macrophages appear after trauma to the brain. To
      investigate the accumulation patterns of reactive microglial cells and
      macrophages after cortical incision, these cells were stained
      immunohistochemically with anti-ED1 antibody in the brain sections before and 1,
      3, 5, and 7 days after incision. And to ascertain the participation of oxygen
      free radicals in these cellular reactions, a synthesized free radical scavenger,
      (+/-)-N,N'-propylenedinicotinamide (AVS) was administered in this model. Rats
      were administered AVS (300 mg/kg, i.p.) 30 min before, 2.5 h and every 24 h after
      incision (AVS group), while only saline was administered in the same manner as a
      control (saline group). In the saline group, both reactive microglial cells and
      macrophages had already appeared on day 1 post-incision. The former continued to
      increase in number during the following days, whereas the latter increased in
      number up to day 3 and thereafter decreased. Both the numbers of reactive
      microglial cells and macrophages were significantly decreased (P < 0.05) in the
      AVS group on days 5 and 7. The results suggest the participation of oxygen free
      radicals in the reaction of microglial cells and macrophages in traumatic brain
      injury.

PMID- 8532219
TI  - On the caudal extension of the X zone in the cerebellar cortex of the rat.
AB  - Following a selective injection of biotinylated dextran amine in the nuclear
      target (the interstitial cell groups, icg) of the X zone of the rat cerebellum,
      retrogradely labelled Purkinje cells (PCs) were found within a longitudinal strip
      of cortex, 250 microns in width, 1000 microns lateral to midline. This labelling
      delineates two compartments in the X zone, one rostral through lobules II-VI, and
      one caudal through lobules VIII-X. The whole rostrocaudal extent of the icg
      appears to be the target of PCs from both compartments without any apparent
      topographical organization.

PMID- 8532220
TI  - Fatigue in COPD.

PMID- 8532221
TI  - Predicting diabetic retinopathy.

PMID- 8532222
TI  - The expanding role of nurses in helping the government combat health care fraud.

PMID- 8532224
TI  - Traveling healthy: a guide for counseling the international traveler.
AB  - Pretravel medical history and itinerary review coupled with education and
      counseling precedes a mutual plan between the provider and the traveler for
      appropriate immunizations, prophylaxis for malaria, and precautions against
      travelers' diarrhea. This article provides a useful tool for taking a travel
      history, an overview of the immunizations recommended, and behavioral practices
      for prevention of illness and injury. Traveler-friendly resources are available
      for pretravel advice, health care abroad, emergency medical transport, special
      needs travelers, and U.S. State Department advisories. Planning should begin as
      early as possible to allow time for vaccine series, separation of vaccines to
      avoid adverse interactions, as well as prophylactic antimalarials that need to be
      initiated in advance of travel. Travelers with special needs should prepare ahead
      for access to care, medications, and medical identification. Returning travelers
      need to be counselled to report their travel to their provider if seeking medical
      attention post travel.

PMID- 8532223
TI  - Fetal alcohol syndrome: diagnosis, management, and prevention.
AB  - Fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE) encompass a pattern
      of birth defects in persons whose mother ingested alcohol during pregnancy.
      Persons with FAE display fewer of the FAS traits. The hallmarks of FAS are pre-
      and postnatal growth retardation, central nervous system dysfunction, and
      characteristic facial dysmorphology. However, its effects can be multi-systemic-
      encompassing the cardiac, skeletal, and muscular systems, as well as presenting
      as lack of coordination, hyperactivity, diminished or distorted sense of danger,
      and lack of ability to function as an independent adult. The frequent incidence
      of this constellation of symptoms has a far-reaching impact (familial, medical,
      educational, and societal) because a myriad of professionals and large amounts of
      funding are used to help manage FAS/FAE children and adults. This article
      identifies, for a primary care provider, the essential characteristics of FAS/FAE
      and discusses available management options. Early diagnosis and continued
      education are advantageous at all levels, benefiting the individual and all of
      society.

PMID- 8532225
TI  - Diagnosis and treatment of allergic rhinitis.
AB  - Allergic rhinitis is frequently seen by primary care providers. Symptoms include
      rhinorrhea, itching of nose and eyes, nasal congestion, and sneezing. They occur
      when the patient is exposed to antigens stimulating mediator release. History is
      essential to assist differential diagnosis and provide education. This article
      reviews common findings of the physical exam, diagnostic testing, and
      differential diagnosis. The first line of treatment is avoidance, followed by
      medications such as antihistamines, decongestants, and nasal steroids. If these
      treatments are not effective, then referral to an allergist is necessary for
      further workup and possible treatment with immunotherapy.

PMID- 8532226
TI  - State regulatory board structure, regulations, and nurse practitioner
      availability.
AB  - State boards of nursing (BON) and medicine (BOM) promulgate regulations that
      affect nurse practitioners (NPs). Certain characteristics of board structure have
      an impact on two potential barriers to NP practice: the absence of direct third
      party reimbursement and authority to prescribe. The percentage of consumers on
      BONs and BOMs increases the likelihood of direct third-party reimbursement for
      NPs. The presence of an NP committee providing input to a board increases the
      likelihood of authority to prescribe for NPs. The availability of NPs is enhanced
      by the presence of NP educational programs in the state, the level of effort by
      the state related to NP recruitment and retention, and the presence of direct
      third-party reimbursement.

PMID- 8532227
TI  - "A tuberculosis control plan for ambulatory care centers".

PMID- 8532228
TI  - Adult counseling for sexually transmitted diseases and HIV infection. U.S. Public
      Health Service.

PMID- 8532229
TI  - "Justifying nurse practitioner existence: hard facts to hard figures".

PMID- 8532230
TI  - Prescriptive authority legislation in Arkansas.

PMID- 8532231
TI  - Advance directives: matters of life and death.

PMID- 8532232
TI  - Control of whooping cough in New Zealand; slow progress.

PMID- 8532233
TI  - Fletcher Challenge-University of Auckland Heart & Health Study: design and
      baseline findings.
AB  - AIMS: The aims of this prospective observational study are to determine the
      relationship of sociodemographic factors, psychological factors and several
      factors measured in blood, with the risk of coronary heart disease (CHD) in a New
      Zealand population. METHODS: Participants were recruited from two sources:
      employees of the Fletcher Challenge Group and individuals listed on the general
      electoral roll for the Auckland region. Baseline and follow up risk factor data
      were obtained from a questionnaire, blood samples and a simple physical
      examination. Outcome data on deaths and hospitalisations due to coronary heart
      disease will be obtained primarily through linkage of participant identifiers to
      data collected nationally by the New Zealand Health Information Service. RESULTS:
      A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge
      and 2518 from the electoral roll), representing a response rate of 74%. Within
      the study population, there was a broad distribution of sociodemographic
      characteristics including ethnicity-10% of participants were Maori and 5% were of
      Pacific Islands origin. There was also wide heterogeneity of coronary heart
      disease risk as judged from the distributions of established risk factors at
      baseline-5% of participants had evidence of existing coronary heart disease, a
      quarter were current smokers, a sixth were nondrinkers, almost a half were
      overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving
      antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L.
      CONCLUSIONS: This is the first, large scale prospective observational study of
      the determinants of coronary heart disease in a New Zealand population. The study
      participants represent a broad cross section of society, with wide variation in
      sociodemographic characteristics and coronary heart disease risk. Initial results
      concerning the relationships of primary interest should be available within 5
      years when sufficient coronary heart disease events have been documented to allow
      reliable analyses.

PMID- 8532234
TI  - The prevalence of fetal alcohol syndrome in New Zealand.
AB  - AIMS: To obtain an estimate of the prevalence of fetal alcohol syndrome in New
      Zealand and to report information on paediatrician surveillance for alcohol
      related birth defects. METHODS: New Zealand paediatricians were asked to complete
      a postal survey. Questions recorded the number of children with alcohol related
      birth defects under their care, and examined the respondents' surveillance for
      alcohol related birth defects. RESULTS: There were 63 children under 10 years of
      age with fetal alcohol syndrome under paediatric care in 1993. The majority of
      paediatricians considered the diagnosis only when risk features were identified:
      the most frequent being children of high risk mothers and children with
      dysmorphic features. CONCLUSIONS: Fetal alcohol syndrome exists in New Zealand.
      The prevalence of fetal alcohol syndrome as estimated in this study is lower than
      would be expected from international prevalence reports and is likely to be an
      underestimate. Current surveillance for alcohol related birth defects depends on
      an individual paediatrician considering the diagnosis only when faced with a
      perceived at risk infant or child, and there is likely under recognition. An
      increased awareness of the risks of alcohol consumption in pregnancy and the full
      spectrum of alcohol related birth defects is required.

PMID- 8532235
TI  - A community's attitudes towards the mentally ill.
AB  - AIM: To assess the general community's knowledge of mental illness and personal
      experience of people with mental illness. METHOD: Three hundred randomly selected
      Dunedin residents were surveyed by a postal questionnaire. The instruments used
      to measure attitudes were a shortened form of the Californian attitudes towards
      mental illness scale (CAMI scale) and a social distance scale. In addition,
      questions were asked about the respondent's age, gender, marital status, level of
      education, their main source of opinion, their experience with the mentally ill,
      and their beliefs about the causes and types of mental illness. RESULTS: Having
      known a person with mental illness facilitates more intimate relationships with
      people with a mental illness. Sociodemographic variables did not predict
      attitudes on the CAMI scale. Most respondents who had been in contact with the
      mentally ill held informed and enlightened views. CONCLUSION: The community needs
      and welcomes information on the subject of mental illness and has a positive
      outlook for the future planning of the rehabilitation of people with mental
      illness.

PMID- 8532236
TI  - A community survey of sun exposure, sunburn and sun protection.
AB  - AIM: To describe outdoor activities, sun protection behaviours and the experience
      of sunburn in a sample of New Zealanders during summer weekends of 1994. METHODS:
      1243 respondents to a telephone survey provided information regarding their
      outdoor activities for the 5 hour period around midday of the previous Saturday
      and Sunday. The sample was drawn from those aged 15 to 65 years in the five
      centres of Auckland, Hamilton, Wellington, Christchurch and Dunedin. Respondents
      provided information on sun exposure, sunburn, sun protection and beliefs about
      tanning, as well as background demographic information, skin type and previous
      experience of sunburn. RESULTS: 12% of the sample (or 17% of all those outdoors)
      reported being sunburned on the preceding weekend, and those sunburned tended to
      be men, and to be under age 35 years. The face, neck and limbs were the areas
      most frequently reported as burned. Sporting activities and beach or water
      activities were associated with the highest number of episodes of burning.
      Overall 38% of those outside reported wearing a hat and 32% reported the use of a
      sunscreen. Positive attitudes to tanning were quite common and probably present
      the main target for change in the community. CONCLUSION: On any sunny weekend in
      summer about three-quarters of adult New Zealanders will be out in the sun for
      relatively long periods of time, and many will get sunburned. The reduction of
      such harmful sun exposures remains an important public health goal.

PMID- 8532237
TI  - Does ethnicity influence obstetric intervention?
AB  - AIMS: To examine whether the high proportion of Polynesian women giving birth at
      Middlemore Hospital contributes to its low interventional delivery rate. METHODS:
      A study of a one-year cohort of women delivering at Middlemore Hospital. Delivery
      suite records were scrutinised to determine ethnicity and mode of delivery.
      Statistical comparisons were made. RESULTS: In Maori, Pacific Island and European
      women the caesarean section rates were 6.5%, 9.5% and 11.5% respectively. Maori
      women have a significantly lower rate of caesarean section than Pacific Island
      women and both groups have a significantly lower rate than European women. The
      spontaneous vaginal delivery rates in Maori, Pacific Island and European women
      were 89.0%, 87.4% and 74.8% respectively. CONCLUSION: The high proportion New
      Zealand Maori and Pacific Island women contributes to, but does not fully
      explain, the low interventional delivery rate at Middlemore Hospital.

PMID- 8532238
TI  - Variation in ANA titres in Auckland.
AB  - AIM: To determine the intralaboratory and interlaboratory variation in reported
      ANA titres in three Auckland laboratories, and to see if this has improved since
      a similar study was performed in 1981. METHODS: Serum samples on 26 subjects with
      rheumatological symptoms were sent to the three laboratories on two separate days
      in 1993, and the presence and titre of ANA determined. RESULTS: The number of
      titre dilutions by which duplicate samples differed within each laboratory has
      decreased since the previous study, and variation within each laboratory of
      greater than two dilutions was not observed. The correlation between the
      laboratories has improved since the previous study, particularly for Lab A vs.
      Lab B. CONCLUSION: The ANA test, as expressed in titres, is more reproducible in
      Auckland laboratories than has been the case in the past.

PMID- 8532239
TI  - Mefloquine and scuba diving.

PMID- 8532240
TI  - Vitamin K prophylaxis in the newborn.

PMID- 8532241
TI  - Leadership for women's health.

PMID- 8532242
TI  - Prevalence of cystic fibrosis mutations in pregnancies with fetal echogenic
      bowel.
AB  - OBJECTIVE: To determine the prevalence of the most common cystic fibrosis
      mutations in pregnancies complicated by fetal echogenic bowel by using DNA
      testing. METHODS: Forty-five pregnancies with fetal echogenic bowel were studied
      prospectively for cystic fibrosis mutations. Using polymerase chain reaction, DNA
      from fetal amniocytes (n = 21), fetal blood (n = 5), or parental blood (n = 19)
      was amplified and tested for delta F508, G551D, G542X, and 621 + 1G-->T cystic
      fibrosis mutations, which account for about 85% of the mutations in the British
      population. In selected cases, further mutations were tested according to the
      parental ethnic background. RESULTS: Only one of the 26 fetuses screened was
      heterozygous for cystic fibrosis mutations. Among 38 parental samples screened
      from the remaining 19 pregnancies, cystic fibrosis mutations were detected in two
      cases, only one of the parents being a carrier in each case. The prevalence of
      cystic fibrosis carrier status in fetal and parental samples (1:26 and 1:19,
      respectively) is within the expected prevalence in the British population (1:25).
      No fetuses were affected by cystic fibrosis in this series, but five were found
      to have growth restriction, two trisomy 21, two congenital infection, and two
      bowel obstruction. CONCLUSION: Our results suggest that ultrasonographic
      detection of fetal echogenic bowel is not associated with an increased prevalence
      of cystic fibrosis mutations in pregnancies at low risk for this disease.

PMID- 8532243
TI  - Abnormal umbilical artery Doppler waveforms and cord blood corticotropin
      releasing hormone.
AB  - OBJECTIVE: To determine whether placental secretion of corticotropin-releasing
      hormone into the fetal circulation is increased in pregnancies complicated by
      umbilical-placental vascular insufficiency. METHODS: Twenty women with abnormal
      Doppler umbilical artery flow velocity waveforms and six women with uncomplicated
      term pregnancies and normal umbilical artery flow velocity waveforms had cord
      blood concentrations of corticotropin-releasing hormone, ACTH, cortisol, and beta
      hCG estimated. RESULTS: The mean cord blood corticotropin-releasing hormone
      concentration was significantly higher in pregnancies with abnormal umbilical
      artery flow velocity waveforms than in normal pregnancies (108 +/- 27 versus 24
      +/- 8 pg/mL, P = .019). Elevated cord blood corticotropin-releasing hormone
      levels were seen in the abnormal group regardless of the presence or absence of
      preeclampsia or fetal growth restriction. There were no significant differences
      in cord blood cortisol, ACTH, or beta-hCG concentrations. CONCLUSION: The
      concentration of corticotropin-releasing hormone in the fetal circulation is
      significantly increased in pregnancies complicated by abnormal umbilical artery
      flow velocity waveforms. This may represent a stress-responsive compensatory
      mechanism in the human placenta.

PMID- 8532244
TI  - Perinatal diagnostic evaluation of velamentous umbilical cord insertion:
      clinical, Doppler, and ultrasonic findings.
AB  - OBJECTIVE: To evaluate the association between velamentous cord insertion and
      adverse pregnancy outcome in singleton pregnancies, and to assess the diagnostic
      usefulness of nonstress testing (NST) and Doppler ultrasound in this condition.
      METHODS: We retrospectively reviewed 12,750 consecutive singleton, chromosomally
      normal pregnancies from July 1989 through December 1993 at the University
      Hospital of Kuopio, Finland. Of these, 216 were complicated by velamentous
      umbilical cord insertion, whereas the remaining 12,534 were normal controls.
      Using multiple regression analysis, we evaluated the risks by noting adverse
      infant outcomes: low birth weight (LBW), small for gestational age (SGA), preterm
      delivery, fetal death, admission to a specific infant care unit, low Apgar
      scores, neonatal acidemia, and abnormal intrapartum fetal heart rate (FHR)
      patterns. At prenatal visits, NST and Doppler ultrasound examinations were
      carried out as a routine part of obstetric care. RESULTS: Even after we
      controlled for confounding factors, velamentous umbilical cord insertion was
      associated with higher risk of LBW (odds ratio [OR] 2.32), SGA (OR 1.54), preterm
      delivery (OR 2.12), low Apgar scores at 1 and 5 minutes (ORs 1.76 and 2.47,
      respectively), and abnormal intrapartum FHR pattern (OR 1.59). Only 5% of the
      patients with abnormal insertion showed pathologic NST results at prenatal
      visits. Ultrasonographic examination was carried out on 80 patients with
      velamentous umbilical cord insertion as a routine part of obstetric care, and in
      only one case was direct visualization of the abnormal insertion successful.
      After we excluded pregnancies with preeclampsia, abnormal umbilical artery
      Doppler velocimetry was found in none of the cases examined (n = 48). CONCLUSION:
      There were substantial differences in pregnancy outcome measures between the
      subjects with velamentous umbilical cord insertion and controls. Current
      antepartum methods of tracing uteroplacental problems are not effective in the
      prenatal detection of abnormal insertion. Therefore, in future studies, the use
      of other diagnostic tools, such as color Doppler imaging of cord insertion,
      should be evaluated in high-risk pregnancies followed-up because of fetal growth
      restriction.

PMID- 8532245
TI  - Fetal heart rate patterns in pregnancies with chromosomal disorders or subsequent
      fetal loss.
AB  - OBJECTIVE: To evaluate whether an abnormal fetal heart rate (FHR) is associated
      with chromosomal abnormalities in pregnant women undergoing an invasive procedure
      for prenatal diagnosis, and to investigate an abnormal FHR's potential value in
      predicting fetal loss in chromosomally normal pregnancies after the procedure.
      METHODS: This was a prospective study including 867 women, all consecutive
      singleton pregnancies at 10-18 weeks' gestation, who underwent chorionic villus
      sampling (n = 371) or genetic amniocentesis (n = 496) at our institution. Fetal
      heart rate, expressed as beats per minute, was measured before the invasive
      procedure. Structural malformations detected by ultrasound were excluded.
      RESULTS: Chromosomal abnormalities were diagnosed in 25 fetuses, including 11
      with trisomy 21. In ten of 25 fetuses with chromosomal abnormalities, the FHR was
      between the fifth and 95th percentiles established before the procedure for the
      chromosomally normal group with normal outcome. Using the fifth percentile as a
      cutoff for trisomy 21, the detection rate was 63.6%, with a specificity of 96.2%
      and a positive predictive value of 17.9% (one in 5.5) in our population.
      Moreover, in six of the ten chromosomally normal miscarriages occurring within 4
      weeks after the procedure, the FHR was above the 95th percentile. CONCLUSION:
      Although the value of a single measurement for screening purposes needs to be
      confirmed by further investigation, our preliminary data suggest that chromosomal
      anomalies, especially trisomy 21, may be suspected in fetuses with an abnormally
      low FHR in early pregnancy. In chromosomally normal fetuses, the detection of an
      abnormally high FHR in some degree may be predictive of fetal loss after the
      invasive procedure.

PMID- 8532246
TI  - Ureaplasma urealyticum infection of the placenta in pregnancies that ended
      prematurely.
AB  - OBJECTIVE: To investigate the relationship between Ureaplasma urealyticum
      infection of the placenta and premature onset of labor. METHODS: We studied 647
      pregnancies that resulted in the live birth of an infant weighing less than 1501
      g. The chorionic surface of the placenta was cultured for U urealyticum,
      Mycoplasma hominis, and group B streptococci. RESULTS: The rate of ureaplasma
      isolation increased with increasing interval between rupture of membranes and
      delivery. When analyses were limited to the 96 singleton pregnancies that ended
      within 1 hour of rupture of membranes and before the 29th week of gestation, U
      urealyticum was prominently associated with an increased risk of premature onset
      of labor (P = .008 unadjusted, and P = .05 when adjustment was made for all
      potential confounders). Ureaplasma infection rate was lowest in pregnancies
      terminated because of severe maternal preeclampsia or progressive fetal growth
      restriction. CONCLUSION: Ureaplasma urealyticum infection is associated with
      premature onset of labor and with increasing duration of time between rupture of
      membranes and delivery. Eradication of ureaplasmas from the urogenital tract of
      women and their partners, ideally before conception, should be considered.

PMID- 8532247
TI  - Accelerated fetal lung maturity profiles and maternal cocaine exposure.
AB  - OBJECTIVE: To determine the effect of maternal cocaine exposure on fetal lung
      maturity as measured by surfactant-albumin ratios determined by the TDx-FLM test.
      METHODS: A case-control study design was used to compare fetal lung maturity as
      assessed by a surfactant-albumin ratio assay (TDx-FLM) in amniotic fluid (AF)
      obtained from women who were known to use cocaine and those who were not known to
      use cocaine during the study pregnancy. Multiple logistic regression procedures
      were used to control for gestational age and possible confounders, such as
      obstetric and nonobstetric complications, other substance abuse, race, infant
      sex, and payer status. RESULTS: Maternal cocaine use during pregnancy was
      associated with an accelerated fetal lung maturity profile (adjusted odds ratio
      [OR] 2.04, 95% confidence interval [CI] 1.04-4.00) as determined by the TDx-FLM
      test. Other variables found to be statistically significant predictors of a
      mature fetal lung profile were cigarette smoking during the current pregnancy (OR
      1.61, 95% CI 1.02-2.56). Preterm labor, preterm rupture of membranes,
      nonobstetric illness during pregnancy, and exposure to other abused substances
      were not associated with accelerated fetal lung maturity. CONCLUSION: Maternal
      cocaine use during pregnancy is associated with a doubling of the probability of
      a mature fetal lung profile as determined by TDx-FLM analysis of AF. Tobacco use
      is also a predictor of accelerated fetal lung maturity profiles.

PMID- 8532249
TI  - Blood gas analysis of placental and uterine blood during cesarean delivery.
AB  - OBJECTIVE: To measure blood gases in uterine venous blood and maternal and fetal
      blood from the placenta, and to characterize gas exchange in the intervillous
      space. METHODS: Blood gas measurements were performed immediately after
      collecting placental and uterine blood from the subchorial and marginal lakes,
      from the chorionic vein and artery in the placenta in utero, and from the uterine
      vein during 12 cesarean deliveries. RESULTS: The mean oxygen pressure (PO2)
      values of the chorionic vein and subchorial lake were 28.7 +/- 6.0 and 29.9 +/-
      7.5 mmHg, respectively, with a difference of 1.2 mmHg. The individual data for
      PO2 of the chorionic vein exceeded those of the subchorial lake in five subjects
      and were almost equal in two of the 12 subjects. The mean values of carbon
      dioxide pressure (PCO2) and bicarbonate were greater in the chorionic vein than
      in the subchorial lake, but the mean pH values were the same in the two groups.
      The mean values of blood gas analysis were not different between subchorial and
      marginal lakes with similar blood composition. The mean PO2 of the uterine vein
      in ten subjects was 45.9 mmHg, significantly higher than that of the subchorial
      lake. CONCLUSIONS: The human placenta may be defined as a multivillous model with
      a high degree of oxygen transfer. Arteriovenous anastomoses are suspected in the
      pregnant uterus beyond 37 weeks' gestation. Subchorial and marginal lakes contain
      similar admixed blood, which circulates and performs gas exchange.

PMID- 8532248
TI  - The usefulness of a urinary LH kit for ovulation prediction during menstrual
      cycles of normal women.
AB  - OBJECTIVE: To assess the predictive value of monitoring urine LH at home using a
      rapid, colorimetric enzyme immunoassay test (Ovuquick) once every evening.
      METHODS: Twenty-six strictly defined normal women with no history of infertility
      were enrolled in studies involving urine LH tests. Each subject had transvaginal
      sonography and serum LH tests performed two times per day beginning in the middle
      of a normal menstrual cycle. All subjects performed urine LH testing at home
      every evening. The time of the peak serum LH measurement was considered the
      surge. Ovulation was determined using sonographic criteria with confirmation by
      normal luteal-phase progesterone levels (3 ng/mL or greater). Two clinically
      relevant intervals were determined: interval I, time from peak serum LH to
      positive urine LH, and interval II, time from positive urine LH to follicular
      collapse by ultrasonography. RESULTS: All 26 cycles examined were ovulatory,
      based on sonographic and progesterone level criteria. The mean time (+/- standard
      error of the mean [SEM]) for interval I was 2 +/- 2 hours (95% confidence
      interval [CI] -2 to 6). The mean time (+/- SEM) for interval II was 20 +/- 3
      hours (95% CI 14-26). Positive predictive values for follicular collapse within
      24 or 48 hours after positive urine LH testing were 73 and 92%, respectively.
      CONCLUSION: Urine LH testing every evening is a reliable method of predicting
      ovulation within the ensuing 48 hours.

PMID- 8532250
TI  - An anatomical approach to oophorectomy during vaginal hysterectomy.
AB  - Oophorectomy is not always performed at the time of vaginal hysterectomy because
      of technical difficulties encountered in visualizing the ovaries and clamping and
      ligating the infundibulopelvic ligament. After uterine removal, a method that
      simplifies the approach involves separating the round ligament along the
      avascular space from the fallopian tube and ovary, then ligating the
      infundibulopelvic ligament separately from the round ligament, rather than
      clamping and ligating the infundibulopelvic and round ligaments together.

PMID- 8532251
TI  - Learning from the community about barriers to health care.
AB  - One of the major challenges facing obstetrician-gynecologists, especially those
      serving populations that are diverse in culture and circumstances, is to identify
      and address the barriers that keep women from seeking timely preventive and
      prenatal health care. The Department of Obstetrics and Gynecology at Rochester
      General Hospital held a community focus groups to learn more about women's
      attitudes toward health care. In addition to economic issues, such as lack of
      insurance and an inability to pay, the organizers found that many of the factors
      that prevent or discourage women from seeking health care involve issues of
      communication and understanding. Many women wanted what they perceived to be
      additional services. In reality, many of the things desired involved changes in
      doctor-patient interactions rather than the addition of any new service, and
      could be addressed with relative ease and minimal cost. Providing staff members
      with training in cultural sensitivity and encouraging them to develop a real
      awareness of patient circumstances are first steps that can lead to better
      communication between provider and patient and to the development of mutual
      trust. Other factors, such as the fear of incarceration or of losing one's
      children if health care is sought, present more serious challenges. Providers of
      care to high-risk, impoverished populations need to develop strong links to
      mental health, substance abuse, and family preservation services that allow them
      to intervene with troubled women and their families with services that are
      alternatives to incarceration and punitive actions.

PMID- 8532252
TI  - Intrauterine contraceptive device-associated actinomycotic abscess and
      Actinomyces detection on cervical smear.
AB  - OBJECTIVE: To summarize clinical features and treatments in reported cases of
      actinomycotic pelvic abscess occurring in women using intrauterine contraceptive
      devices (IUD), and to review detection of Actinomyces by cervical smear. DATA
      SOURCES: The English-language medical literature accessed through MEDLINE.
      METHODS OF STUDY SELECTION: We identified 92 cases of actinomycotic abscesses
      associated with IUD use in 63 case reports. In addition, 31 studies of
      Actinomyces detection were found, 16 of which were studies of Papanicolaou smear
      based detection. DATA ABSTRACTION AND SYNTHESIS: Data regarding clinical
      presentation and treatment were culled from case reports, whereas detection rates
      of Papanicolaou smear and other methods were obtained from studies of Actinomyces
      detection. The average patient was 37 years old, had been using an IUD for 8
      years, and presented with abdominal pain, weight loss, vaginal discharge, and
      fever. Laboratory studies commonly revealed anemia, leukocytosis, and an elevated
      erythrocyte sedimentation rate. Most of these patients underwent operative
      procedures, usually hysterectomy and salpingoophorectomy. High-dose penicillin
      was found to be an effective antibiotic. Detection rates of organisms on
      Papanicolaou smear were somewhat variable; use of other detection methods,
      including endometrial biopsy, culture, and immunofluorescence, did not improve
      this variability. CONCLUSIONS: Pelvic actinomycosis associated with the use of
      IUDs can mimic pelvic malignancy; for that reason, it is often treated
      surgically. However, if the diagnosis of actinomycosis can be obtained
      preoperatively, antibiotic treatment may lead to complete resolution. The
      Papanicolaou smear may be useful in evaluating such patients.

PMID- 8532253
TI  - Pumps and warmers during amnioinfusion: is either necessary?
AB  - OBJECTIVE: To determine if there is evidence from published reports that the use
      of infusion pumps or solution warmers during amnioinfusion is beneficial. DATA
      SOURCES: We identified all English-language amnioinfusion reports published since
      1983 through Medline and references. METHODS OF STUDY SELECTION: Fourteen
      prospective papers with at least 40 subjects were identified. DATA EXTRACTION AND
      SYNTHESIS: For the amnioinfusion and control groups in each study, odds ratios
      (OR) were calculated for cesarean delivery, fetal distress, meconium below the
      cords, low 5-minute Apgar score, and endometritis. Cumulative ORs were calculated
      using the Mantel-Haenszel inverse variance method. This process was repeated
      after separation into pump-gravity and warmed-unwarmed groups. Multiple
      regression analyses were performed. Amnioinfusion improved the ability of the
      fetus to tolerate labor (fetal distress OR 0.40), decreased the incidence of
      meconium below the cords (OR 0.16), and decreased the rate of cesarean delivery
      (OR 0.56). There were no demonstrable benefits associated with the use of warmers
      or pumps. In multiple regression analysis, infusion pumps were associated with a
      significantly increased risk of fetal distress (P = .01). CONCLUSION: The use of
      amnioinfusion is associated with a decreased risk of fetal distress, meconium
      below the cords, and cesarean delivery. To date, there is no demonstrable benefit
      using infusion pumps or solution warmers during amnioinfusion.

PMID- 8532254
TI  - Clinical research in ancient Babylon: methodologic insights from the Book of
      Daniel.

PMID- 8532255
TI  - Comparison of the effects of meperidine and nalbuphine on intrapartum fetal heart
      rate tracings.

PMID- 8532256
TI  - Introducing evidence-based medicine into a department of obstetrics and
      gynecology.

PMID- 8532257
TI  - Vesicouterine fistula: a rare complication of vaginal birth after cesarean.

PMID- 8532258
TI  - Cost-effectiveness of in vitro fertilization.
AB  - OBJECTIVE: To estimate the cost per woman delivered of pregnancies from an in
      vitro fertilization (IVF) program, and to assess what factors contribute to the
      cost. METHODS: The cost during 2 years' experience of a single IVF program was
      analyzed retrospectively. Cost analysis included cost of the IVF procedure itself
      as well as costs incurred because of maternal and neonatal complications.
      RESULTS: The major contributor to the total cost of IVF was high-order multiple
      pregnancies. The cost per woman delivered of singleton or twin pregnancies was
      approximately $39,000, whereas the cost per woman delivered of triplet and
      quadruplet pregnancies was approximately $340,000. CONCLUSION: In vitro
      fertilization can be cost-effective if steps are taken to minimize high-order
      multiple (triplet or more) pregnancies.

PMID- 8532259
TI  - Electroejaculation and assisted reproductive techniques for anejaculatory
      infertility.
AB  - OBJECTIVE: To report our experience with electroejaculation combined with
      intrauterine inseminations (IUI) and other assisted reproductive technologies.
      METHODS: Anejaculatory men desirous of fertility were evaluated in our Assisted
      Reproductive Program. Between March 1991 and December 1994, 26 men (age 24-48)
      underwent a total of 84 electroejaculations. Causes of anejaculation included
      spinal cord injury (n = 23) and retroperitoneal lymph node dissection (n = 3).
      Female partners were super-ovulated to improve the pregnancy rate. The success in
      sperm retrieval and pregnancy rates were determined, and the quality of
      electroejaculates was evaluated. RESULTS: Seventy-seven of 84 (92%)
      electroejaculations were successful, defined by retrieval of more than 10 x 10(6)
      total and more than 10(6) motile spermatozoa. Mean sperm count was 65 million/mL
      (range 0-569), but mean motility was only 16% (range 0-66). Mean normal
      morphology was 27% (range 0-71). Ten couples attempted conception. Fifty cycles
      of IUIs were performed, resulting in four normal term infants and one spontaneous
      abortion (pregnancy rate 10% per IUI). One patient failed to conceive with eight
      cycles of IUIs but became pregnant with in vitro fertilization-embryo transfer
      with micromanipulation using electroejaculates; she delivered a set of healthy
      twins. Two couples elected donor sperm insemination after failing to conceive by
      IUI with electroejaculates; both became pregnant. CONCLUSION: Electroejaculation
      offers an encouraging pregnancy opportunity for anejaculatory men who otherwise
      are considered infertile. Marked asthenospermia is observed in electroejaculates,
      the etiology of which remains obscure. Further studies to elucidate the cause may
      improve pregnancy rates.

PMID- 8532260
TI  - Comparison of probe sheaths for endovaginal sonography.
AB  - OBJECTIVE: To compare the effectiveness of commercially available probe covers
      with less expensive condoms. METHODS: During a 10-month period, sonographers
      performed endovaginal ultrasound examinations on patients by randomly testing
      either commercially available probe covers or condoms on the vaginal probe. After
      use, the sheaths were tested for damage by filling them with water to observe for
      leakage and thereby determine the breakage rate. RESULTS: Perforations were noted
      in 15 of 180 probe covers and three of 180 condoms (8.3 versus 1.7%, P < .05;
      relative risk [RR] 5.4, 95% confidence interval [CI] 1.4-18.5). Potential
      contamination of the endovaginal probe occurred during nine of 174 examinations
      and one of 178 examinations in which probe covers and condoms, respectively, were
      used (P < .05; RR 9.7, 95% CI 1.2-67.7). CONCLUSION: Condoms are less expensive
      and superior to commercially available probe covers for covering the ultrasound
      probe during endovaginal examinations.

PMID- 8532261
TI  - Lactation after augmentation mammoplasty.
AB  - OBJECTIVE: To compare the lactation outcomes of breast-augmented women and
      nonaugmented women. METHODS: This study used a retrospective, comparative design.
      Demographic and descriptive data were obtained from client records maintained by
      a lactation support program at a large children's hospital in the southwest
      United States. The association between breast augmentation and lactation outcome
      in the two groups was investigated by obtaining data from these existing records.
      RESULTS: A significantly greater incidence of lactation insufficiency was found
      in augmented women compared with nonaugmented women (P < .001). Among 42
      augmented women, 27 (64%) had insufficient lactation, compared with only three
      (less than 7%) of the 42 nonaugmented women. Augmented women who experienced
      sufficient lactation were equivalent in age, ethnicity, type of delivery,
      smoking, previous breast-feeding experience, and lactation course compared to
      augmented women with lactation insufficiency. However, the type of breast
      incision was significantly associated with lactation outcome. More specifically,
      it was the periareolar approach that was most significantly associated with
      lactation insufficiency (P < .01). The incidence of lactation insufficiency with
      the submammary-axillary approach was only statistically significant when compared
      with nonaugmented women. CONCLUSION: A significantly greater incidence of
      insufficient lactation was found among augmented women compared with nonaugmented
      women. The periareolar approach was most significantly associated with lactation
      insufficiency.

PMID- 8532262
TI  - Transvaginal mobilization and removal of ovaries and fallopian tubes after
      vaginal hysterectomy.
AB  - OBJECTIVE: To describe a technique of transvaginal mobilization and removal of
      ovaries and tubes, and to assess its use in older women undergoing vaginal
      hysterectomy. METHODS: Charts of 151 women age 50 and older who underwent vaginal
      hysterectomy by one senior gynecologic surgeon during 1991-1993 were reviewed.
      RESULTS: Ninety of 138 women (65%) who chose ovarian removal had their ovaries
      successfully removed vaginally. In 48 women, one or both ovaries were examined
      and noted to be normal, and they were not removed or could not be removed
      vaginally. Operating time, estimated blood loss, length of hospital stay, and
      rates of intraoperative complications and postoperative morbidity did not differ
      significantly in the bilateral salpingo-oophorectomy and ovarian conservation
      groups. CONCLUSION: Transvaginal removal of ovaries and tubes can be achieved in
      about two-thirds of women undergoing vaginal hysterectomy with minimal or no
      increases in operating time and surgical morbidity.

PMID- 8532263
TI  - Peritoneal closure at vaginal hysterectomy: a reassessment.
AB  - OBJECTIVE: To evaluate the clinical outcome of patients who underwent vaginal
      hysterectomy with or without peritoneal closure. METHODS: This study was a
      randomized trial. Using computer-generated numbers, all patients undergoing
      vaginal hysterectomy without oophorectomy were randomized to either no peritoneal
      closure (n = 57) or routine peritoneal closure (n = 49). Patients were followed
      up for a minimum of 1 year for development of complications and postoperative
      dyspareunia. At 4-6 postoperative weeks, the distance between the ovaries and the
      vaginal cuff was measured by ultrasound. RESULTS: Postoperative complications
      were similar in both groups. The incidence of deep-thrust dyspareunia at 6 and 12
      months was also similar. No statistical differences between the two groups were
      noted in the ovary to vaginal cuff distances either overall or when patients with
      dyspareunia were considered separately. CONCLUSION: The data in this study do not
      support the use of reperitonealization on a routine basis. However, because of a
      lack of statistical power, larger studies will be required to confirm this
      theory.

PMID- 8532264
TI  - The surgical anatomy of needle bladder neck suspension.
AB  - OBJECTIVE: To define the surgical anatomy of needle bladder neck suspension in
      order to explain this operation's effect on urethral support and gain information
      useful in minimizing intraoperative complications. METHODS: Needle bladder neck
      suspension was carried out on two unembalmed, multiparous cadavers. After fixing
      the suspensory sutures in place, the pelvis of one cadaver was completely
      dissected. The second cadaver was serially sectioned at 1-cm intervals, and the
      sections were subjected to both anatomic and histologic examination. These
      findings were correlated with the findings noted during an autopsy dissection of
      a woman who previously had undergone needle bladder neck suspension at our
      institution and with our surgical experience with this operation. RESULTS: The
      plane of dissection used to enter the space of Retzius lay between the vaginal
      mucous membrane and the visceral endopelvic fascia. The point of entry into the
      retropubic space lay between the levator ani muscles and its superior fascia,
      lateral to the arcus tendineus fasciae pelvis, the paraurethral vascular plexus,
      and bladder neck. It was cephalad to the perineal membrane (urogenital
      diaphragm). The paraurethral supporting tissues incorporated in the suspensory
      suture included the portion of the endopelvic fascia that lies between the vagina
      and urethra and, usually, the arcus tendineus fasciae pelvis. Attaching the
      suspensory sutures in needle bladder neck suspension seems to stabilize the
      bladder neck by providing a new point of lateral fixation for its supporting
      endopelvic fascia. CONCLUSION: Needle bladder neck suspension stabilized the
      supportive fascia of the urethra, and vascular injury may be minimized by
      detailed knowledge of paraurethral anatomy.

PMID- 8532265
TI  - Postoperative catheterization, urinary retention, and permanent voiding
      dysfunction after polytetrafluroethylene suburethral sling placement.
AB  - OBJECTIVE: To determine the incidence of permanent voiding dysfunction after
      polytetrafluoroethylene suburethral sling placement, and to assess the effect of
      voiding mechanism and uroflowmetry on the duration of postoperative
      catheterization. METHODS: Between January 1986 and April 1991, 108 patients
      underwent suburethral sling procedures to treat genuine stress incontinence.
      Medical records were reviewed to collect urodynamic and catheterization data. One
      year or longer after surgery, 98 women completed a telephone interview evaluating
      incontinence, self-catheterization, and voiding symptoms. RESULTS: The mean
      duration of postoperative cathtrerization was 10.7 weeks. There was no
      significant relationship between preoperative uroflow indices and the duration of
      catheterization. The presence of a preoperative detrusor contraction was
      associated with a shorter mean duration of postoperative catheterization (6.1
      versus 14.8 weeks, P = .07) and a lower risk of sling removal for retention (7
      versus 33%, P = .04). Eight patients continued self-catheterization. Fourteen
      patients reported other micturition problems: three used the Crede maneuver or
      double voided to facilitate emptying and 11 were unable to urinate when seated
      upright. There was no correlation between the duration of catheterization and
      ongoing voiding dysfunction. Among nine women who underwent further surgery to
      treat postoperative urinary retention, three continue to catheterize, one
      performs Crede, and one urinates standing. CONCLUSIONS: Polytetrafluoroethylene
      suburethral sling placement commonly produces permanent voiding difficulty.
      Patients who void without a detrusor contraction are at increased risk for
      prolonged postoperative catheterization. Sling removal does not ensure resolution
      of urinary retention and may be no better than leaving the sling in place.

PMID- 8532266
TI  - The prevalence of dysmenorrhea, dyspareunia, pelvic pain, and irritable bowel
      syndrome in primary care practices.
AB  - OBJECTIVE: To determine the prevalence of dysmenorrhea, dyspareunia, pelvic pain,
      and irritable bowel syndrome in a clinical population of reproductive-age women.
      METHODS: A ten-page questionnaire was administered to a consecutive sample of
      women age 18-45 years who were approached in the waiting areas of two obstetrics
      and gynecology practices and three family medicine practices in central North
      Carolina. Of 701 women approached to fill out the questionnaire, 581 (83%)
      returned completed forms suitable for analysis. RESULTS: The reported prevalence
      of dysmenorrhea, dyspareunia, pelvic pain, and irritable bowel syndrome was 90,
      46, 39, and 12%, respectively. Low income was found to be a risk factor for
      dysmenorrhea and dyspareunia, and African-American race was found to be a risk
      factor for pelvic pain. Pelvic pain was also more common among women 26-30 years
      old. Otherwise, dysmenorrhea, dyspareunia, pelvic pain, and irritable bowel
      syndrome were not associated with age, parity, marital status, race, income, or
      education. CONCLUSION: Dysmenorrhea, dyspareunia, pelvic pain, and irritable
      bowel syndrome are common complaints among women of reproductive age and are not
      consistently associated with demographic risk factors. Therefore, inquiry about
      these pelvic pain complaints should be a routine part of health care for women.

PMID- 8532267
TI  - Heterogeneous etiology of squamous carcinoma of the vulva.
AB  - OBJECTIVE: To correlate various previously identified risk factors, different
      histologic types, and the presence of human papillomaviruses (HPV) in squamous
      vulvar carcinomas and intraepithelial precursor lesions. METHODS: Cases of
      squamous vulvar carcinomas and intraepithelial precursor lesions from a case
      control study were analyzed by histologic type, the presence of HPV, and HPV
      type. These findings were correlated with demographic and interview data.
      RESULTS: Significant differences (P < .001) in the prevalence of HPV DNA were
      noted between the following: 1) patients with high-grade vulvar intraepithelial
      neoplasia (VIN) (48 of 54 [88.9%]), 2) different types of squamous carcinomas,
      designated basaloid and warty carcinomas (18 of 21 [85.7%]), and 3) keratinizing
      squamous carcinoma (three of 48 [6.3%]). When the risk factor profiles for
      basaloid or warty carcinoma and keratinizing squamous carcinoma were compared, it
      was found that basaloid and warty carcinoma was significantly associated with the
      classical cervical cancer risk factors (lifetime number of sexual partners, age
      at first intercourse, abnormal Papanicolaou smears, venereal warts, low
      socioeconomic status, and cigarette smoking) whereas keratinizing squamous
      carcinoma was less strongly linked to these factors and in some cases not at all.
      The risk profile for VIN was similar to that of basaloid and warty carcinoma
      (with respect to sexual and reproductive history and smoking), although effects
      were weaker for some factors. CONCLUSION: The results of this study further
      support the view that vulvar carcinoma has two different etiologies, one related
      to HPV infection and one that is not.

PMID- 8532268
TI  - Reduced mortality associated with long-term postmenopausal estrogen therapy.
AB  - OBJECTIVE: To compare all-cause and specific-cause mortality rates in women who
      had or had not used long-term postmenopausal estrogen replacement therapy (ERT).
      METHODS: We identified women who used long-term postmenopausal ERT and compared
      them with a sample of age-matched postmenopausal nonusers. Through linking of
      these subjects' medical record numbers to various data bases, we examined
      survivorship and cause of death among estrogen users and nonusers. The risk of
      death in 232 postmenopausal women who began ERT within 3 years of menopause and
      used it for at least 5 years was compared with that of 222 age-matched
      postmenopausal nonusers. In the users, the mean length of estrogen use was 17.1
      years. RESULTS: Statistically significant reductions in all-cause mortality were
      found in users compared with nonusers. For death from any cause, the age-adjusted
      relative risk (RR) and associated 95% confidence interval (CI) in estrogen users
      was 0.54 (0.38-0.76). The reduction in all-cause mortality was largely due to
      reductions in coronary heart disease (RR 0.40, CI 0.16-1.02) and other
      cardiovascular disease (RR 0.27, CI 0.10-0.71). Overall cancer mortality was
      similar in the two groups (RR 0.85, CI 0.46-1.58), although estrogen users had a
      higher risk of death from breast cancer (RR 1.89, CI 0.43-8.36) and lower risk of
      death from lung cancer (RR 0.22, CI 0.04-1.15). CONCLUSION: Long-term ERT use is
      associated with lower all-cause mortality and confers this apparent protection
      primarily through reduction in cardiovascular disease.

PMID- 8532269
TI  - Repair of transversely incised abdominal wall fascia in a rabbit model.
AB  - OBJECTIVE: To compare several commonly used methods of closing transversely
      incised anterior abdominal wall in order to determine which technique results in
      the strongest incisional tensile strength. METHODS: Thirty-six rabbits were
      randomized to receive either interrupted or continuous closure with 0-Vicryl.
      Within these groups, each animal was randomized to one of three different bite
      and interval techniques: 1-cm bites/0.5-cm intervals, 1-cm bites/1-cm intervals,
      and 2-cm bites/1-cm intervals. Each rabbit received three to four transverse
      abdominal wall incisions of approximately 3-8 cm in length. The incisions were
      excised en bloc and stored at -70C at postoperative week 1, 2, or 4 in a random
      fashion. Representative 1-cm strips were harvested from each incision after
      thawing. The Instron tensiometer was used to determine the maximum intrinsic
      tensile strength required to disrupt each tissue strip at the incision.
      Statistical analysis was performed using analysis of variance, two-sample t test,
      Scheffe multiple comparison, and Kruskal-Wallis test. RESULTS: Two hundred thirty
      seven strips were analyzed. The mean maximum tensile strength of all of the
      interrupted and continuous suture repairs was 48 and 38 lb, respectively (P <
      .001). The maximum tensile strength for interrupted closures was achieved at week
      1 and was similar at week 4. The continuous closure was weakest at week 1 and
      increased to a maximum value during week 4. There was no difference in maximum
      tensile strength between the interrupted and continuous closure groups at week 4.
      There was no significant difference in the maximum tensile strength of the three
      repair techniques. The mean maximum tensile strength of all specimens was
      significantly less among those harvested during weeks 1 and 2 compared with week
      4 (P = .001). CONCLUSION: In this randomized study, the interrupted closure had a
      greater maximum tensile strength than the continuous closure in repair of
      transverse incisions during the first 2 postoperative weeks. Both repair methods
      were associated with a similar maximum tensile strength at 4 postoperative weeks.
      Repair techniques using different bite sizes and intervals resulted in similar
      maximum tensile strengths.

PMID- 8532270
TI  - Acyclovir suppression to prevent cesarean delivery after first-episode genital
      herpes.
AB  - OBJECTIVE: To determine if suppressive acyclovir therapy given to term gravidas
      experiencing a first episode of genital herpes simplex virus (HSV)-infection
      during pregnancy decreases the need for cesarean delivery for that indication.
      METHODS: Forty-six pregnant women with first episodes of genital herpes during
      pregnancy were randomly assigned to receive oral acyclovir 400 mg or placebo,
      three times per day, from 36 weeks' gestation until delivery as part of a
      prospective, double-blind trial. Herpes simplex virus cultures were obtained when
      patients presented for delivery. Vaginal delivery was permitted if no clinical
      recurrence was present; otherwise, a cesarean was performed. Neonatal HSV
      cultures were obtained and infants were followed-up clinically. RESULTS: None of
      the 21 patients treated with acyclovir and nine of 25 (36%) treated with placebo
      had clinical evidence of recurrent genital herpes at delivery (odds ratio [OR]
      0.04, 95% confidence interval [CI] 0.002-0.745; P = .002). No woman treated with
      acyclovir had a cesarean for herpes, compared with nine of 25 (36%) of those
      treated with placebo (OR 0.04, CI 0.002-0.745; P = .002). No patient in either
      treatment group experienced asymptomatic genital viral shedding at delivery. No
      neonate had evidence of herpes infection or adverse effects from acyclovir.
      CONCLUSION: Suppressive acyclovir therapy reduced the need for cesarean for
      recurrent herpes in women whose first clinical episode of genital HSV occurred
      during pregnancy. Suppressive acyclovir treatment did not increase asymptomatic
      viral shedding and was not harmful to the term fetus.

PMID- 8532271
TI  - A randomized controlled trial of aspirin in patients with abnormal uterine artery
      blood flow.
AB  - OBJECTIVE: To evaluate color Doppler imaging of the uterine arteries as a
      screening test in nulliparous women, and to examine the role of low-dose aspirin
      therapy in pregnancies with abnormal uteroplacental resistance. METHODS: At the
      routine 18-week fetal morphology ultrasound scan, 955 nulliparous women underwent
      color Doppler imaging of the uterine arteries. Abnormal uteroplacental vascular
      resistance was defined with respect to both the systolic-diastolic ratio of the
      flow velocity waveform and the presence of an ipsilateral early diastolic notch.
      Those with abnormal uterine artery waveforms were asked to participate in a
      randomized controlled trial of aspirin therapy. Pregnancy outcomes were compared
      in women with normal or abnormal flow velocity waveforms, as well as in the two
      arms of the intervention study. RESULTS: Of 186 women with abnormal
      uteroplacental resistance according to criteria defined previously, 102 agreed to
      randomization to either low-dose aspirin (100 mg/day) or placebo for the
      remainder of the pregnancy. Abnormal uterine artery flow velocity waveforms were
      associated with statistically significant increases in preeclampsia (11 versus
      4%), birth weight below the tenth percentile (28 versus 11%), and adverse
      pregnancy outcome (45 versus 28%). Prophylactic aspirin therapy did not result in
      a significant reduction in pregnancy complications. CONCLUSION: Abnormal
      uteroplacental resistance at 18 weeks' gestation was associated with a
      significant increase in adverse pregnancy outcome. Low-dose aspirin did not
      reduce pregnancy complications in women with uteroplacental insufficiency.

PMID- 8532272
TI  - Urinary calcium in asymptomatic primigravidas who later developed preeclampsia.
AB  - OBJECTIVE: To assess the efficacy of calciuria as a diagnostic test for the
      prediction of preeclampsia. METHODS: We asked young healthy primigravidas from
      the prenatal clinic in our hospital to collect a 24-hour urine sample at 17-20
      weeks' gestation. Urinary calcium was measured and expressed as calciuria per 24
      hours (mg/24 hours), urinary excretion of calcium per 24 hours on a basis of body
      weight (mg/kg/24 hours), and as the calciuria-creatinuria ratio (mg/mg). For each
      test, sensitivity, specificity, predictive values, and relative risk (RR) were
      calculated. The test with the best overall performance was determined by
      comparing receiver operating characteristic curves. Sixty-nine patients completed
      the study until the end of the puerperium, and 15 of them were diagnosed with
      preeclampsia. RESULTS: The most efficient test was the urinary excretion of
      calcium per 24 hours based on body weight. Using 3.4 mg/kg/24 hours as a cutoff
      point, we obtained a sensitivity of 80% (95% confidence interval [CI] 59.8-100),
      specificity 64.8% (95% CI 52.1-77.5), positive predictive value 38.7% (95% CI
      21.6-55.8), negative predictive value 92.1% (95% CI 83.5-100), and RR 4.9 (95% CI
      1.5-15.8). CONCLUSION: In young, apparently healthy primigravidas, a low urinary
      excretion of calcium per kilogram of body weight per 24 hours before the end of
      the first half of gestation is a risk factor for preeclampsia, with an acceptable
      sensitivity and high negative predictive value, but with a positive predictive
      value no better than chance.

PMID- 8532273
TI  - Adolescence and very low birth weight infants: a disproportionate association.
AB  - OBJECTIVE: To examine the incidence of very low birth weight (VLBW) neonates,
      defined as those weighing less than 1500 g, delivered by adolescents compared
      with the general obstetric population. METHODS: A retrospective observational
      study of 16,857 women delivering live-born infants from January 1, 1989, to June
      30, 1993, was conducted at the University of Arizona Health Sciences Center.
      Adolescents were defined as those having a maternal age of 18 years or less at
      the time of delivery. The rate of VLBW infants delivered to adolescent mothers
      was compared with the general obstetric population (women at least 19 years old)
      using chi 2 analysis, multiple analysis of variance, and multiple linear
      regression. RESULTS: During the study period, 204 VLBW infants were delivered,
      yielding an overall VLBW delivery rate of 1.2%. Adolescents had a VLBW delivery
      rate that was considerably higher than the general obstetrical population: 35 of
      1758 (2.0%) versus 169 of 15,099 (1.1%) (P = .002). Whereas adolescents accounted
      for 10.6% of the total deliveries during the study period, they delivered 17% of
      the VLBW neonates. The relative risk of an adolescent delivering a VLBW infant
      was 1.7 (95% confidence interval 1.2-2.2). CONCLUSION: Preterm birth is one of
      the major unresolved problems in modern obstetrics. Although the association
      between adolescence and preterm birth has been reported previously, specific
      attention has not been focused on the VLBW neonate. We conclude that adolescents
      deliver a disproportionate number of VLBW infants.

PMID- 8532274
TI  - Fetal hyperinsulinism at 14-20 weeks and subsequent gestational diabetes.
AB  - OBJECTIVE: To examine the predictive value of amniotic fluid (AF) insulin at 14
      20 weeks' gestation for subsequent gestational diabetes and macrosomia in
      unselected gravidas 35 years or older at time of genetic amniocentesis. METHODS:
      We identified 296 pregnancies through stored AF samples from genetic
      amniocenteses (collected March 1987 through August 1992) in women meeting the
      following criteria: age 35 years or older, amniocentesis at 14-20 weeks,
      performance of a 50-g glucose challenge test, and adequate delivery data.
      RESULTS: A modified double-antibody radioimmunoassay reliably measured AF insulin
      with a detection limit of 0.35 microU/mL. Pregnant women in whom gestational
      diabetes was later diagnosed had higher median AF insulin levels than women who
      did not (0.60 versus 0.42 microU/mL, respectively; P = .026). A stepwise logistic
      regression analysis of gestational age at amniocentesis, maternal second
      trimester weight, maternal age, and log AF insulin value on gestational diabetes
      showed only AF insulin to have a significant association with gestational
      diabetes (P = .004). Seven of 21 cases of gestational diabetes had AF insulin
      values exceeding the 95th percentile (1.33 microU/mL) compared with only 14 of
      275 women with normal glucose tolerance (P < .001). Amniotic fluid insulin did
      not predict macrosomia in either nondiabetic or gestational diabetic pregnancies.
      CONCLUSION: Gestational diabetes is associated with increased AF insulin at 14-20
      weeks, suggesting augmentation of fetal insulin production in the early fetal
      period in at least some cases of gestational diabetes.

PMID- 8532275
TI  - Elevations of amniotic fluid macrophage inflammatory protein-1 alpha
      concentrations in women during term and preterm labor.
AB  - OBJECTIVE: To determine whether elevated concentrations of macrophage
      inflammatory protein-1 alpha (MIP-1 alpha) in amniotic fluid (AF) are related to
      term and preterm labor. METHODS: Amniotic fluid was obtained from women from five
      different clinical situations: 1) term cesarean delivery, no labor (n = 29); 2)
      normal term labor, no infection (n = 36); 3) preterm labor, delivery more than 1
      week from sampling, no infection (n = 19); 4) preterm labor, delivery within 1
      week from sampling, no infection (n = 18); and 5) preterm chorioamnionitis (n =
      8). Amniotic fluid was collected aseptically at the time of amniocentesis,
      amniotomy, or hysterotomy. Concentrations of MIP-1 alpha were determined by
      enzyme-linked immunosorbent assay. Statistical analysis was by Wilcoxon rank-sum
      test, Kruskal-Wallis test, and unpaired t test. RESULTS: Women in normal term
      labor had significant elevations of AF MIP-1 alpha concentrations when compared
      with women at term undergoing repeat cesarean delivery (P < .001). In women with
      term gestation, AF MIP-1 alpha correlated well with cervical dilation (r2 =
      0.479, P < .001). In women with preterm labor who later delivered within 1 week
      of presentation, AF MIP-1 alpha concentrations were higher than those from women
      who did not deliver within 1 week. Women who presented with clinically evident
      chorioamnionitis had the highest concentrations of AF MIP-1 alpha (P = .001).
      CONCLUSION: Women in labor have significantly elevated AF concentrations of MIP-1
      alpha, particularly if labor is associated with intrauterine infection. We
      suggest that MIP-1 alpha is involved in the physiology of normal labor and in the
      pathogenesis of infection-associated preterm labor.

PMID- 8532276
TI  - The effect of manual removal of the placenta on post-cesarean endometritis.
AB  - OBJECTIVE: To determine if intraoperative glove change and placental delivery
      method affect the post-cesarean endometritis rate. METHODS: After informed
      consent, women who required cesarean were randomly assigned to one of four study
      groups: 1) no glove change plus manual placental extraction, 2) no glove change
      plus spontaneous placental delivery, 3) glove change plus manual extraction, and
      4) glove change plus spontaneous delivery. Bilateral glove change by both primary
      and assistant surgeons occurred immediately after delivery of the newborn and
      before delivery of the placenta. External uterine massage and traction on the
      umbilical cord were performed to assist spontaneous delivery of the placenta. A
      first-generation cephalosporin was routinely administered after umbilical cord
      clamping for prophylaxis of post-cesarean endometritis. RESULTS: Of 760 women
      entered into the study, we included 643 who did not have intrapartum
      chorioamnionitis or cesarean hysterectomy. The four groups were comparable with
      respect to selected maternal and intrapartum characteristics, including maternal
      and gestational age, parity, presence of labor, and the presence and duration of
      membrane rupture. The postoperative endometritis rate was significantly higher in
      women whose placentas were extracted manually (31 versus 22%, P = .01). Operator
      glove change did not alter the incidence of endometritis (relative risk 1.0, 95%
      confidence interval 0.79-1.3). CONCLUSION: Manual extraction of the placenta is
      associated with a significantly greater risk of post-cesarean endometritis than
      that observed with assisted spontaneous placental delivery. Intraoperative glove
      change does not decrease post-cesarean endometritis.

PMID- 8532277
TI  - Intracameral sodium hyaluronate before fistulization.

PMID- 8532278
TI  - Pigment dispersal syndrome.

PMID- 8532279
TI  - Chemosis following blepharoplasty.

PMID- 8532280
TI  - A practical guideline for management of endophthalmitis.

PMID- 8532281
TI  - Ptosis repair and blepharoplasty in the adult.
AB  - When contemplating upper lid ptosis and blepharoplasty surgery, preoperative
      evaluation is essential so that the patient and the surgeon have similar
      expectations as to the final result of the surgery. Blepharoplasty and ptosis
      repair can be performed as a combined procedure in the adult. The procedure
      involves excising excess skin and underlying orbicularis muscle, and in some
      cases, orbital fat. The levator aponeurosis is advanced onto the tarsus and the
      excess levator excised. An eyelid crease is formed during closure by passing a
      suture through the advanced aponeurosis.

PMID- 8532282
TI  - Astigmatic and refractive stabilization after cataract surgery.
AB  - We assessed the timing of astigmatic and refractive stabilization following six
      cataract surgery procedures with intraocular lens implantation in 229 eyes
      divided into six groups in the following incision sizes and methods of wound
      closure: 11-mm incision with running suture closure (26 eyes) 6.5-mm incision
      with running suture closure (29 eyes) 6.5-mm incision with single horizontal
      suture closure (25 eyes) 6.5-mm incision without suture closure (46 eyes) 5.5-mm
      incision without suture closure (51 eyes) 3.2-mm incision without suture closure
      (52 eyes) Analyzed up to 6 months postoperatively were: the mean and standard
      deviation of axis-based keratometric cylinders the absolute value of the induced
      cylinder vector the spherical equivalent of the refractive power. In the 11- and
      6.5-mm incision running suture groups, these parameters did not stabilize during
      the study period. In the 6.5-mm incision horizontal suture and sutureless groups,
      the values stabilized at 3 months postoperatively; in the 5.5-mm incision group,
      at 1 month; and in the 3.2-mm incision group, at 2 weeks. These results indicate
      that the appropriate point at which to prescribe postoperative correction
      spectacles differs significantly depending on the procedure, and that smaller
      incisions with wound-closure methods that do not exert vertical force are
      associated with fewer postoperative refractive changes.

PMID- 8532283
TI  - Long-term surgical results of combined trabeculotomy ab externo and cataract
      extraction.
AB  - Trabeculotomy ab externo has been demonstrated to be effective in controlling
      intraocular pressure (IOP) in adult patients with either primary open-angle
      glaucoma or pseudoexfoliation syndrome. We evaluated the surgical outcome of 60
      eyes with either primary open-angle glaucoma or pseudoexfoliation syndrome that
      underwent combined trabeculotomy ab externo and cataract extraction. All patients
      were at least 40 years old, and were followed for at least 1 year. At the final
      examination, IOP was well controlled (21 mm Hg or less) in 54 (90%) of the 60
      eyes, with or without medication. Also, "overall success" (ie, stabilization of
      IOP, visual field, and optic nerve status) was achieved in 49 (81.7%).
      Complications included fibrin exudation (22%), transient IOP elevation (17%),
      early perforation of the probe into the anterior chamber (10%), and detachment of
      Descemet's membrane (5%). We recommend combined trabeculotomy ab externo and
      cataract extraction in selected cases of glaucoma with coexisting cataract. For
      cases in which the target IOP level is in the low teens, or for patients who may
      not tolerate postoperative fluctuations in IOP, we do not recommend trabeculotomy
      ab externo. Also, in eyes that have normal-tension glaucoma, or that have already
      sustained severe damage to the optic nerve, visual dysfunction caused by
      glaucomatous changes may progress even after successful combined trabeculotomy ab
      externo and cataract extraction.

PMID- 8532284
TI  - Therapeutic penetrating keratoplasty in nonhealing corneal ulcer.
AB  - Results of penetrating keratoplasty in 443 eyes of 439 patients of active
      infective corneal ulcers, from a period of 10 years, were analyzed. All these
      eyes were proven refractory to maximal medical therapy for extended periods of
      time, in some cases more than 6 weeks. As the surgery was performed during the
      active stage, the outcome was not favorable functionally. Clinical cure was
      obtained, however, by therapeutic penetrating keratoplasty in all but 27 of these
      eyes. Of unsuccessful cases, 16 could be saved with additional medical therapy,
      two led to phthisis bulbi, and nine required repeat therapeutic penetrating
      keratoplasty. Complications encountered included disturbances in intraocular
      dynamics such as extrusion of the lens and vitreous during surgery, secondary
      rise of intraocular pressure leading to damage of the optic nerve, loss of the
      eye due to above factors, and reinfection. The anatomical success achieved was
      97% with graft clarity of 2+ or more in 39% of eyes. Useful vision, ie, better
      than or equal to 6/60, was possible in 33% of eyes. Thus, therapeutic
      keratoplasty in refractory corneal ulcer still has scope in a Third-World
      country.

PMID- 8532285
TI  - Direction and location of retinotomy for removal of subretinal neovascular
      membranes.
AB  - We describe two cases in which a new retinotomy technique is used to remove
      subretinal neovascular membranes. The direction and location of the retinotomy
      are of ultimate importance in prevention of damage to retinal nerve fibers and
      the corresponding visual field loss. The retinotomy is made with an angled 20
      gauge needle in nondiathermized retina. The direction of the retinotomy is
      parallel to the nerve fiber layer and located over the subretinal neovascular
      membrane. No laser retinopexy was necessary after removal of the subretinal
      neovascular membrane.

PMID- 8532286
TI  - Amblyopia in congenital ptosis.
AB  - This study evaluates the association between congenital ptosis and amblyopia.
      Amblyopia was detected in 7 of 36 (19%) patients with congenital ptosis. Two
      patients (6%) with amblyopia had no contributing factors other than the presence
      of congenital ptosis. A statistically significant correlation between severe
      nonocclusive ptosis (greater than or equal to 4 mm) and the development of
      amblyopia was identified. No new cases of amblyopia developed after surgical
      repair of the ptosis, suggesting early surgery for severe nonocclusive congenital
      ptosis may decrease the incidence of amblyopia.

PMID- 8532287
TI  - Posterior segment triple surgery after traumatic eye injuries.
AB  - Cataract extraction, posterior chamber intraocular lens (PC-IOL) implantation,
      and complete vitrectomy combined in a one-stage procedure were performed in 16
      eyes (16 patients) with traumatic eye injuries undergoing anterior lensectomy
      (seven eyes), extracapsular cataract extraction (six eyes), or pars plana
      lensectomy (three eyes). Membrane peeling and intraocular foreign-body removal
      (13 eyes, 6 with intraretinal foreign bodies) were performed as needed. Surgery
      was performed from 1 week to 10 years after injury. After an average follow up of
      8 months, 13 eyes (81%) had a visual acuity of at least 20/200; 50%, at least
      20/40.

PMID- 8532288
TI  - Dislocation of cataractous lens by enzymatic zonulolysis: a suggested solution to
      the problem of the 18 million individuals blind from cataracts in Third-World
      countries.
AB  - There are 18 million persons blind from cataracts in Third-World countries and
      the number is doubling every 20 to 25 years. It is impossible to cure this many
      blind with present sophisticated surgical techniques. Enzymatic dislocation of
      the cataractous lens could be performed by nonmedical personnel and the patients
      given inexpensive mass-produced spectacles, which could solve this tremendous
      problem.

PMID- 8532289
TI  - Combined phacoemulsification, endoscopic ciliary process photocoagulation, and
      intraocular lens implantation in glaucoma management.
AB  - The safety and efficacy of combined cataract extraction and intraocular lens
      (IOL) implantation with endoscopic ciliary process photocoagulation in glaucoma
      management was evaluated. Ten patients with uncontrolled open-angle glaucoma and
      cataract prospectively underwent concomitant phacoemulsification, endoscopic
      ciliary process photocoagulation, and posterior chamber IOL implantation. With a
      mean follow up of 19.2 months, the mean intraocular pressure (IOP) decreased from
      31.4 mm Hg preoperatively to 13.5 mm Hg postoperatively, an absolute decrease of
      57%. This represented a significant decrease for each of the patients. The visual
      acuity of each also improved. Transient vitreous hemorrhage developed in one
      patient, but no cystoid macular edema or any other significant complications
      occurred and all eyes were quiet. There were no lens implant dislocations. There
      was no progressive visual field loss at 1 month post surgery, but such loss was
      noted in one patient 1 year after treatment. Good IOP control on no medical
      therapy was attained in one half of the patients. It may be concluded that this
      combined procedure provided effective management of cataract and glaucoma with a
      minimum of postoperative care. The safety and efficacy of this approach as
      compared with cataract surgery combined with filtration remains to be determined.

PMID- 8532290
TI  - Holmium laser sclerostomy via corneal approach with transconjunctival mitomycin-C
      in rabbits.
AB  - We studied the use of the holmium laser for sclerostomy through a small lamellar
      corneal incision and the effects of transconjunctival mitomycin-C on the outcome
      of filtration surgery without conjunctival incision. The holmium laser, equipped
      with a straight-firing probe, was used to create sclerostomies in seven New
      Zealand white rabbits through a corneal lamellar incision. One eye in each rabbit
      was treated with transconjunctival mitomycin-C (0.4 micrograms/mL for 5 minutes),
      and the fellow eye underwent sclerostomy without pretreatment with mitomycin-C as
      a control. The reduction in intraocular pressure was greater and persisted
      significantly longer in the eyes pretreated with mitomycin-C than in the
      controls. All control eyes had flat blebs by day 7 to 12, while the treated eyes
      maintained a bleb throughout the study. Microscopic examination showed that
      sclerostomies created by the straight-firing probe induced significantly less
      thermal damage than those created by the stationary side-firing probe. These
      results demonstrate that successful transcorneal sclerostomy without conjunctival
      incision can be created using the straight-firing holmium laser probe, with
      enhancement of filtration by pretreatment with transconjunctival mitomycin-C.

PMID- 8532291
TI  - Keratoprosthesis as an aid to learning surgical techniques on cadaver eyes.
AB  - Practice on cadaver eyes can be an essential aid for residents and inexperienced
      surgeons in learning operative techniques. Cadaver eyes, however, have been of
      only limited utility for teaching highly complicated procedures because of the
      obscuring of intraocular structures caused by the rapid post mortem onset of
      corneal swelling. We have overcome this problem by the use of a silicone
      keratoprosthesis that provides an excellent view of all intraocular tissues. Our
      model allows the use of donor eyes unsuitable for transplantation and facilitates
      the learning of even complicated cataract surgery, and vitrectomy techniques on
      the human eye. It thus can reduce the rate of complications in operations on
      patients.

PMID- 8532292
TI  - The use of a silicone strip over the sclerotomy in vitreous surgery.
AB  - We have developed a technique to prevent enlargement and distortion of the
      sclerotomy wound during vitreoretinal surgery. The technique involves the use of
      a silicone strip temporarily attached to the sclera. The strip and the sclera are
      pierced with a lance-tipped blade and surgery is done by entering through the
      silicone strip and then through the resulting scleral opening. Such a procedure
      prevents undesirable enlargement of the sclerotomy induced by trauma to the wound
      caused by instruments that can occur in cases of previously damaged sclera or in
      thin sclera associated with high myopia. It also prevents leaks through the wound
      as instruments are withdrawn.

PMID- 8532293
TI  - A central dystonia causes spastic lower eyelid entropion: a hypothesis.
AB  - This article presents a novel hypothesis on what causes an involutional
      entropion. The theory herein proposes that the pathophysiology of entropion is
      that of an idiopathic dystonia with the locus of dysfunction posed in the rostral
      brain stem and with stimuli for its causation mediated through the seventh
      cranial nerve--the facial nerve--by a cord of fibers making its path to the
      upper, ie, temporooculo-zygomatic ramus of the nerve. In a word, involutional
      entropion is but a variant of essential blepharospasm and one of the clinical
      entities within the oculo-oro-facial-cervical family of dystonia disorders.

PMID- 8532294
TI  - Vertical tripod fixation (VTF) simplifies transscleral approaches.
AB  - Transscleral fixation of intraocular lenses (IOL) is an accepted procedure today.
      Following Malbran's initial approach, new techniques have been developed in
      various ophthalmic centers; many, however, are time-consuming and difficult, as
      reflected by complications, most commonly hyphema and IOL tilt. We present here a
      simple method of transscleral fixation, which was performed in 24 patients in our
      department. It involves fixating the IOL vertically, on a three-point
      configuration, using standard 10-0 prolene stitches. Performing it is easy and
      time-saving. VTF ensures a stable transscleral fixation of an IOL.

PMID- 8532295
TI  - Delayed tarsal eversion following periorbital trauma.
AB  - Delayed onset of upper lid edema with exuberant chemosis developed in a 3-year
      old girl following blunt periorbital trauma. Examination under anesthesia
      demonstrated a tightly everted upper tarsus that focally compressed the
      underlying conjunctiva at the superior tarsal border. Injection of
      subconjunctival hyaluronidase followed by local compression and temporary
      tarsorrhaphy resulted in rapid resolution of the chemosis and restoration of the
      normal lid position.

PMID- 8532296
TI  - Tissue plasminogen activator in the surgical excision of subfoveal choroidal
      neovascular membranes.
AB  - We investigated the use of tissue plasminogen activator (t-PA) as an adjunct to
      the surgical removal of subfoveal choroidal neovascular membranes. t-PA in a
      concentration of 6 micrograms/0.1 cc dissolved the fibrin rim surrounding recent
      subfoveal membranes but was less effective on more mature lesions. t-PA may be a
      useful intraoperative tool to limit the damage to surrounding structures during
      the surgical excision of recent subfoveal choroidal neovascular membranes with
      surrounding fibrin rims.

PMID- 8532297
TI  - Oncocytic adenocarcinoma of the lacrimal sac: report of a case with paranasal
      sinus and orbital extension.
AB  - A 92-year-old man has had multiple recurrent oncocytic tumors involving the right
      paranasal sinuses and orbit. A benign oncocytoma that arose from the right
      lacrimal sac was initially diagnosed at age 80 years. The tumor recurred at 3 and
      7 years after initial resection. There was greater histologic atypia in the first
      recurrent tumor, which extended into the right paranasal sinuses. The second
      recurrence had zones on oncocytic adenocarcinoma exhibiting prominent nuclear
      atypia and mitotic activity; this tumor massively invaded the right paranasal
      sinuses and orbit. We describe the clinical and pathologic features of this rare
      case.

PMID- 8532298
TI  - Dacryoadenitis presenting with eyelid retraction.

PMID- 8532299
TI  - Bilateral posterior lenticonus.

PMID- 8532300
TI  - Absorption of ammonia by high water content hydrogel lenses: an inexpensive
      method of analysis.
AB  - Few studies have been done on the absorption and release of chemical vapors by
      high water content hydrogel lenses. In this study we investigated the absorption
      of ammonia vapors by this type of contact lens (CL). Ten high water content
      hydrogel lenses were exposed to vapor generated in a cuvette by 1 drop of aqueous
      ammonia. The contact lens was transferred to a 0.9% saline solution containing a
      colorometric indicator for ammonia and the amount of ammonia released into the
      saline was measured. We found that significant quantities of ammonia were
      absorbed into the lenses and the relation between average concentration of
      ammonia vapor and amount absorbed per contact lens was nearly linear from 50
      parts per million (ppm) to 250 ppm ammonia vapor. For concentrations greater than
      250 ppm there appears to be a saturation effect. Our findings indicate that high
      water contact lenses will absorb ammonia and release it into a solution similar
      to tears.

PMID- 8532301
TI  - Impact resistance of Transitions Plus spectacle lenses.
AB  - Although it has been shown that photochromic glass industrial lenses do not
      provide adequate occupational impact protection, they are frequently requested by
      outdoor workers wanting sunglasses. The recent introduction of Transitions Plus
      (TP), a photochromic plastic lens, may meet the needs of these workers. The
      impact resistance of 60 TP lenses of dress thickness was studied using a
      ballistic test. Lenses were edged and mounted in metal industrial frames. The
      completed spectacles were placed on a headform for ballistic testing using a 6.5
      mm (1/4 in) steel ball propelled from an airgun. The lenses were divided into
      test groups that received: (1) a single impact at the geometrical center by a
      ball traveling at 18 m/s (59 ft/s) and (2) 50 consecutive impacts at 18 m/s, or
      (3) a single impact at 46.5 m/s (152 ft/s). All lenses passed the single impact
      test at 18 m/s. Four lenses broke under repeated impact. All lenses subjected to
      the high-speed impact test failed, either breaking or being dislodged from the
      frame. These findings show that dress thickness TP lenses provide impact
      protection from small blunt missiles traveling at moderate speed, and that they
      are durable under repeated low energy impact. However, thicker lenses must be
      used when the wearer has a high risk of ocular exposure to small high-speed
      missiles in the workplace. It can be concluded that TP lenses may be used in
      occupational eyewear for many outdoor workers who want photochromic sunglass
      lenses, provided that other needs for vision and occupational safety are also
      satisfied.

PMID- 8532302
TI  - Flash visual evoked potential (VEP) in amblyopia and optic nerve disease.
AB  - Amblyopia and optic atrophy are two very different causes of unilateral long
      standing visual impairment. Yet, in some patients the differential diagnosis is
      not always manifest and standard clinical tests may fail to provide accurate
      information. We tested the efficacy of a nonstandard clinical test [flash visual
      evoked potentials (VEP's)] and quantitative multivariate statistical techniques
      as aids in the assessment of this differential. Thirty-three patients were
      separated into four groups (normal, anisometropic amblyopia, strabismic
      amblyopia, and unilateral optic atrophy). Non-patterned flash VEP's were obtained
      using several different temporal frequency rates. Patients with optic atrophy had
      significantly reduced VEP's in the affected eye at all temporal frequencies.
      Strabismic amblyopes, but not anisometropic amblyopes, often showed supranormal
      responses in the affected eye at the higher temporal frequencies. Finally, by
      using discriminant analysis (DA) we were able to classify correctly almost 70% of
      the patients, well above chance level of 25%. This DA provided very good
      sensitivity and specificity. We have shown that the use of flash VEP's and of
      multivariate statistical techniques may provide an effective way to diagnose
      amblyopia differentially from optic atrophy.

PMID- 8532303
TI  - Hyperacuity test to evaluate vision through dense cataracts; research preliminary
      to a clinical study. I. Studies conducted at the University of California at
      Berkeley before travel to India.
AB  - BACKGROUND. Patients with dense ocular media disorders retain the ability to
      project or point to an intense source of light. Using this response capability
      and high luminance points of light as stimuli, Vernier judgments (a hyperacuity
      test) can be made by these patients, even without the presence of a "window"
      through a leucoma, cataract, or bleed. Without coaching, these individuals are
      able to locate the centers of the individual degraded point images if the
      individual light sources are adequately separated (i.e., if sufficient "gaps"
      exist between the individual stimuli), and they can spatially align the degraded
      images. Advanced cataracts are the main cause of blindness in the developing
      world, and this is a treatable condition. In these nations, only a modest
      proportion of affected patients receive surgery, and only 5% or less of these
      individuals obtain treatment in two eyes. There are incredibly large and rapidly
      growing backlogs of advanced cataract patients requiring care (many millions).
      Because of the 20 to 30% failure rates that occur after treatment (all causes) in
      many developing world settings, a test performed before surgery, which offers a
      meaningful estimate of postsurgical visual outcome, can be valuable. Using the
      principle defined above, we seek to determine before surgery those individuals
      who will derive most benefit from cataract removal, and which of two cataractous
      eyes has the better postsurgical visual prognosis. EXPERIMENTAL. In Berkeley, we
      performed a series of preliminary studies on a Vernier acuity test before
      initiating a clinical study in a developing world setting. These studies were
      conducted upon young adult normal subjects wearing their usual vision
      corrections, with and without induced refractive errors, and/or with or without
      simulated dense nuclear cataracts. We sought (1) to determine the number of
      repeat trials necessary for reliable outcomes; (2) to compare a two-point and a
      three-point Vernier acuity display; (3) to determine the shape of the measured
      response function at large gap separations between test points; (4) to define
      optimal test distance and stimulus size; (5) to assess the effect(s) of a broad
      range of uncorrected refractive errors upon outcomes; and (6) to consider means
      to minimize refraction-based errors by using a pinhole, a refractive correction,
      and/or selective spatial filtering. We compared responses obtained using the
      current CRT/VDT-based, computer-driven (Berkeley) instrument with a new precision
      optical/mechanical computer-driven (India) instrument. The India instrument is
      needed to determine design parameters for a next stage simpler, cheaper, more
      rugged field instrument(s).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8532304
TI  - Hyperacuity test to evaluate vision through dense cataracts; research preliminary
      to a clinical study. II. Initial trials of the India instrument and HASP protocol
      at Aravind Eye Hospital, Madurai, India.
AB  - BACKGROUND. Our purpose is to develop a clinical test capable of assessing vision
      through dense cataracts (and other advanced media opacities) before surgery.
      Because such anomalies are endemic in the developing world, it was desirable to
      conduct a clinical study of a prototype India instrument and HyperAcuity Study
      Protocol (HASP) in such a setting. This investigation, preliminary to a planned
      clinical study, was conducted at the Aravind (Free) Eye Hospital, Madurai, India.
      EXPERIMENTAL. The preliminary HASP protocol, developed in Berkeley, was adapted
      to existing clinical practices in Madurai. Included was a new test of visual
      acuity, the Gap "VA" test, developed as part of the revised protocol. The
      rational for this test, methods used, and sample data are presented. A Vernier
      alignment test (one of the hyperacuities) is used to assess vision through dense
      ocular media disorders. The task of the patient is to align vertically three high
      luminance, discrete visual stimuli. The revised HASP protocol and adapted India
      instrument were tested upon patients with advanced cataracts. The cataract
      grading system used in these studies (provided by Drs. N. V. Projna and G.
      Rohini) is defined. Patients were tested before and shortly after surgery. This
      investigation allowed us to refine the test protocol and instrument design
      preparatory for a clinical study of HASP. A much simpler/cheaper version of the
      India instrument will be used in the planned clinical study. Additional
      experiments are scheduled in order to address issues which require resolution
      before initiation of next-stage testing. In part, in these papers, we seek to
      help others understand some problems encountered when conducting research in a
      developing world environment, even a very good one!

PMID- 8532305
TI  - Ultrastructural visualization of lectin receptors in normal and injured
      epithelium of the rabbit cornea.
AB  - Lectin receptors of the rabbit corneal epithelium were investigated
      ultrastructurally using gold-conjugated lectins. Corneal epithelium with an
      intact mucous layer was readily labeled with wheat-germ agglutinin (WGA), whereas
      after mechanical or chemical removal of the mucus, labeling was minimal,
      suggesting that the lectin receptors were located mainly in the mucus. Corneal
      epithelium subjected to slight superficial injury was also labeled with WGA. In
      this case, however, the gold particles were in close contact with the cell
      membrane of injured and/or newly exposed cells. In the more injured cells, gold
      particles were seen in the cytoplasm as well. Labeling with WGA indicates the
      presence of sialyl residues, known to be attachment sites for Pseudomonas
      aeruginosa. The results suggest a protective role of mucus against infection. The
      association of WGA lectin receptors with the plasma membrane of compromised
      corneal epithelial cells may help to explain the mechanism of bacterial invasion
      of the cornea, e.g., in overnight wear of contact lenses with insufficient oxygen
      transmissibility.

PMID- 8532306
TI  - Influence of the luminance signal and red-green and yellow-blue opponent
      chromatic signals in figural-stimuli stereograms.
AB  - The influence of color signals on stereopsis has been studied using figural
      stimuli stereograms with variations introduced according to the opponent
      chromatic channels (red-green and yellow-blue), derived from Boynton's color
      vision model. We used wallpaper stereograms, which enable the rank-order
      disparity ranges of the chromatic and luminance signals to be compared with the
      rank-order disparity range of proximity, a particular spatial configuration of
      the stereogram in which there are no variations in chromaticity and/or luminance.
      The results indicate that both chromatic signals contribute to stereopsis as does
      the luminance signal, contradicting the model of Hubel and Livingstone. The
      results also show there are no clear dependencies upon the kind of signal
      processed, as luminance and chromatic variations are processed with the same
      efficiency.

PMID- 8532307
TI  - Small amounts of chromatic aberration influence dynamic accommodation.
AB  - The prevailing view of accommodation is that the eye changes focus to maximize
      luminance contrast by trial and error. Negative feedback is considered essential
      in this view because luminance contrast provides no directional information.
      Fincham proposed an alternate view in which longitudinal (axial) chromatic
      aberration (LCA) provides a directional stimulus for accommodation. For spatial
      frequencies above approximately 0.5 cpd contrast of the retinal image is
      different for long, middle, and short spectral waveband components of the image.
      We varied the amount of LCA in small steps (0.25 D) to determine how much LCA is
      needed to enhance or impair the response. An infrared optometer monitored
      accommodation continuously while subjects viewed a yellow/black square-wave
      grating (3.5 cpd) in a Badal stimulus system. The yellow/black grating was
      produced by superimposing red (600 nm) and green (520 nm) gratings, and LCA was
      increased, decreased, neutralized, and reversed by repositioning the red grating
      component along the axis of the optical system. Target vergence was modulated
      sinusoidally (0.2 Hz) over a 1 D range (1.5 to 2.5 D) and gain and phase-lag of
      the accommodation response were determined by Fourier analysis. Subjects
      accommodated well as long as a normal amount of LCA was present--0.5 D in the
      correct direction enhanced accommodative gain, and 0.25 D in the reverse
      direction markedly inhibited the response. We conclude that the contrast of the
      retinal image in different spectral wavebands specifies focus of the eye, and
      provides a powerful directional stimulus for reflex accommodation.

PMID- 8532308
TI  - Colorimetric analyses of various light sources for the D-15 color vision test.
AB  - Colorimetric analyses were performed in both normal trichromatic and dichromatic
      color spaces to determine whether several light sources were suitable illuminants
      for the Farnsworth-Munsell Panel D-15 (D-15) color vision test. Results for
      fluorescent lamps showed that lamps with a correlated color temperature (CCT) of
      7200 degrees K and a general color rendering index (GCRI) of at least 90 are
      acceptable substitutes for illuminant C. Predictions for filtered tungsten light
      indicated that lights with a color temperature near 5000 degrees K are unsuitable
      because of nonuniformities in the glass daylight filter transmittance.
      Conclusions based on these analyses are conservative because, with exception of
      the GCRI, color adaptation effects were not taken into account.

PMID- 8532309
TI  - Recording eye movements using coaxial cameras--applications for visual ergonomics
      and reading studies.
AB  - We developed a system of coaxial video cameras that records monocular eye
      position and scene, and superimposes these images using a digital video mixer. We
      mounted miniature video cameras above and below a cube beam-splitting prism in
      the spectacle plane. An infrared emitting diode was imaged in the cornea to
      locate eye position. The technique was accurate to about 0.5 degrees within 15
      degrees of primary gaze; however, we see its main advantages as being its low
      cost and simple design that, for some applications, does not require complex
      computer analysis and data manipulation. With improved camera optics, it has the
      potential for helmet mounting and use remote from a recording console. We used
      the instrument to monitor a reader's eye position when using low vision devices,
      and see applications of the technique in the field of visual ergonomics and
      sports vision.

PMID- 8532310
TI  - Menopausal hormone replacement therapy.

PMID- 8532311
TI  - Ocular health status of chemical industrial workers.

PMID- 8532312
TI  - [Pediatrics before the millennium].
AB  - The 70 year anniversary celebration of the Pediatric Department of University
      Medical School, Debrecen provided an opportunity for the author to survey the
      characteristic features of Pediatrics: the development of this discipline during
      the last decades, its diagnostic and therapeutic facilities and future
      perspectives. Pediatrics responsible for the healthy status, undisturbed
      development, and helping the 20-25% of the population to become healthy grown up
      has gone through a significant change during the past years. In diagnostics the
      new imaging methods, endoscopic procedures and the molecular genetic
      investigations have provided a considerable progress. In therapy application of
      immunoglobulins followed by cytokines, the organ transplantation and gene therapy
      are of basic importance concerning the present facilities and future
      perspectives. In order to become familiar with the developing possibilities, the
      latest scientific results physicians are required to carry out self-education. To
      suit the challenges properly physicians are in need not only of professional
      knowledge but also of empathy, sympathy to meet the demands on behalf of the
      patients to a larger extent.

PMID- 8532313
TI  - [Importance of cerebrovascular reactivity testing in diabetes mellitus].
AB  - Diabetes mellitus results in macro- and microangiopathies. Early diagnosis and
      preventive treatment of the cerebral vessel complications may influence the
      prognosis of the disease. The aim of the present work is to summarize the recent
      results of the cerebral hemodynamic studies in diabetics. A suitable, non
      invasive screening method for diagnosis of the altered cerebral arteriolar
      function is discussed.

PMID- 8532314
TI  - [Screening of patients waiting for kidney transplantation].
AB  - The authors summarise the indications and contraindications of kidney
      transplantation according to their our experiences. They report the changes of
      the number of kidney transplantation in Hungary, the distribution of the kidney
      diseases and they also report the risk factors, which can influence the results
      of the kidney transplantation.

PMID- 8532315
TI  - [Hand and arm vibration syndrome caused by mechanical screw driver].
AB  - Authors performed angiological, neurological and radiological examination of 17
      persons working with power screw-drivers. Vibration measurement of the tools was
      made too. 10 patients had symptoms and signs corresponding to the hand-arm
      vibration syndrome. The vibration of some tools exceeded the maximal allowable
      acceleration level according to ISO 5349. On the ground of the results authors
      conclude that some power screw-drivers can cause hand-arm vibration syndrome. The
      importance of choosing of the right tools and the significance of the periodical
      examinations are underlined in the prevention of the damages.

PMID- 8532316
TI  - [True malignant mixed tumor of the parotid gland (carcinosarcoma)].
AB  - True malignant mixed tumor (carcinosarcoma) is a rare salivary gland tumor. In
      contrast to malignant mixed tumor, which means carcinoma ex pleomorphic adenoma
      in true malignant mixed tumor both carcinomatous and sarcomatous features are
      present in the same tumor. This report presents the case of a 43 year old man
      with a carcinosarcoma of the right parotid gland. Carcinomatous component was
      high grade ductal carcinoma. Mesenchymal component showed the features of giant
      cell type malignant fibrous histiocytoma. The diagnosis was supported by positive
      staining for cytokeratin in the carcinomatous part and positive vimentin, alpha-1
      antitrypsin and CD 68 staining in the sarcomatous part of the tumor.
      Ultrastructural investigation confirmed the diagnosis. Multinucleated osteoclast
      type giant cells are probably of reactive origin.

PMID- 8532317
TI  - [Participation of Adolf Kussmaul in Semmelweis' lectures in Vienna].

PMID- 8532318
TI  - [Changes in hospital bed numbers in Hungary].

PMID- 8532319
TI  - [The role of vascular nitric oxide (NO) in the pathomechanism of pre-eclampsia].
AB  - The significance of nitric-oxide as a biological mediator is increasingly
      elucidated in various physiological processes. In addition to the endothelium
      dependent vasodilator effect it also plays an important role as a
      neurotransmitter. Possible synthesis of endothelial nitric-oxide is an essential
      factor in the regulation of blood pressure and utero-placental circulation.
      Recently the relationship of nitric-oxide and preeclampsia has extensively been
      studied. The results of human studies and animal experiments suggest that
      insufficient production of endothelial nitric-oxide probably has an important
      role in the pathomechanism of preeclampsia.

PMID- 8532320
TI  - [Treatment possibilities for extensive pulmonary embolism as an alternative to
      the Trendelenburg operation].
AB  - The authors describe the clinical course of successfully treated patients with
      extensive, subtotal pulmonary embolism. After the diagnosis was confirmed by
      isotopic scan or pulmonary angiography, mechanical thrombus destruction was
      applied followed by low dose loco-regional thrombolysis in 11 patients by
      streptokinase. Five patients were treated with ultrahigh dose of streptokinase
      through peripheral vein, one patient via pulmonary artery catheter and one
      patient was treated with high dose urokinase by pulmonary catheter in combination
      with mechanical thrombus destruction by guide wire. All the treatment procedures
      were proved to be successful. After detailed case reports, the authors review the
      life saving thrombolytic treatment of acute subtotal pulmonary embolism as an
      alternative of Trendelenburg operation.

PMID- 8532321
TI  - [Basic principles of current trends in the management of hypertension and kidney
      disease in pregnancy].
AB  - The approach to renal disease and hypertension in pregnancy has dramatically
      changed over the past two decades. As opposed to the past, now almost all the
      female patients with underlying renal disease can have successful pregnancy, and
      we are able to manage most of the renal complications occurring during the
      pregnancy. In this article the authors give an extensive review of the results of
      recent studies, concerning this subject. The options to prevent the predictable
      complications, the most recent therapeutic guidelines and the outcome of these
      patient's pregnancies are discussed, focused on the changes, compared to the
      recent past.

PMID- 8532322
TI  - [Recombinant human erythropoietin in the treatment of anemic patients undergoing
      chemotherapy for cancer].
AB  - Twenty-seven anemic patients with malignant tumour who received chemotherapy were
      treated with recombinant human erythropoietin (r-HuEPO). The objective of this
      study was to evaluate the effect of r-huEPO on hematologic and quality of life
      parameters as well as on transfusion requirement in patients with anemia
      secondary to cancer and cyclic chemotherapy. Patient population was allocated
      into two groups based on the chemotherapeutic regimens: 1. cisplatin containing
      and 2, non cisplatin containing regimen. Using 2 g/dl increase in haemoglobin
      levels as the criteria for response, twenty women responded to r-huEPO treatment.
      The response was more marked in the cisplatin group. R-huEPO treatment saved
      transfusion in both groups. Again, less patients required transfusion among those
      treated with cisplatin. There was a marked improvement in the quality of life
      which was more pronounced in patients who responded to r-huEPO treatment and in
      those receiving non cisplatin chemotherapy. No serious adverse experiences
      occurred. In conclusion, two third of patients with anemia secondary to cancer
      and cyclic chemotherapy can be effectively treated with r-huEPO. R-huEPO
      treatment invariably saves transfusion and is highly effective in improving
      quality of life. Adverse reaction is exceptional.

PMID- 8532323
TI  - [Chronic IgM mesangioproliferative glomerulonephritis].
AB  - In their ten years renal biopsy material authors found nine cases of chronic
      glomerulonephritides with predominantly IgM deposition in the mesangium which
      reach the diagnosis of IgM nephropathy. This paper on the basis of a typical case
      deal with the immunopathology, diagnosis, prognosis and therapy of the disease.

PMID- 8532324
TI  - [Experience with chronic hemodialysis in diabetic patients with kidney failure].
AB  - Between 1978 and 1992, 534 patients--including 35 (25 IDDM and 10 NIDDM)
      diabetics--were accepted to chronic hemodialysis (HD) at our Dialysis Center. The
      1-year cumulative survival rate (CSR) was significantly lower in diabetic vs. non
      diabetic group (66 +/- 8% vs. 78 +/- 2%), p < 0.05). At the onset of diabetes the
      mean age of IDDM patients vs. NIDDM patients was 18.2 +/- 2.7 years vs. 51.3 +/-
      3.1 years, respectively. At the beginning of HD treatment the mean age of IDDM
      patients vs. NIDDM patients was 38 +/- 2.4 years vs. 58.3 +/- 2.6 years. In IDDM
      group until the start of HD treatment the mean duration of diabetes was 20 +/-
      1.3 years and it did not depend on the quality of preuraemic metabolic control (p
      = 0.825); mean duration of diabetes until their death was 22.5 +/- 1.3 years.
      Mean age of IDDM and NIDDM patients at their death was 38.8 +/- 3 years and 60.5
      +/- 3.7 years. Average duration of HD treatment was 16 +/- 2.5 months in IDDM
      group and 21.5 +/- 5.8 months in NIDDM group. Major causes of death were
      cardiovascular complications of diabetes (39%) and infections (33%). We found no
      difference in CSR related to gender, age, type of diabetes, quality of metabolic
      control during the HD treatment, but CSR was significantly higher in patients
      with good metabolic control from the onset of diabetes (1-year CSR of adequately
      vs. poorly controlled diabetics: 80% vs. 62%, p < 0.05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8532325
TI  - [Treatment of Basedow-Graves disease in pregnancy].
AB  - Thyrostatic treatment of pregnant women with Graves' disease is a special
      problem. Observation of 46 pregnancies of 35 women suffering from Graves' disease
      has been summarized. The outcome was successful in 45 cases. Methimazole and
      propylthiouracil was administered to the patients without thyroxine. Therapy was
      needed for the two thirds of the mothers. At the end of the second trimester the
      thyrostatic agent could have been withdrawn in the 77% of the cases. Antithyroid
      treatment administered in low dose at the time of conception did not affect the
      outcome. Premature delivery rate and the number of neonates with low weight did
      not increased. Transient hyperthyrotropinaemia was observed in one case.
      Likewise, one infant suffered from neonatal thyrotoxicosis. 37% of the mothers
      had postpartal recurrence of hyperthyroidism. CONCLUSIONS: the free thyroxin
      level monitoring is essential during thyrostatic treatment. Thyrotropin receptor
      antibody investigation, having predictive value for neonatal thyrotoxicosis,
      should be done, too. Postpartal thyroid control is necessary for elucidate a
      hyperthyroid relapse, the rate of which was almost 40%.

PMID- 8532326
TI  - [Sero-epidemiologic study of Epstein-Barr virus markers in patients without
      mononucleosis at a department for infectious diseases].
AB  - The authors have screened sera samples of 1817 unselected patients of not having
      infectious mononucleosis, admitted to their department, for Epstein-Barr virus
      (EBV) viruscapsid (VCA) IgM and IgG type antibody to detect the actual situation
      of EBV infection. The results were evaluated in age groups and in serological
      patterns. Their results indicated, that 80% of children became seropositive by 5
      10 years of age and after 20 years, the rate of seropositivity was over 90%
      comparable to the reports from "developing" countries. IgM VCA antibodies were
      found in 103 samples (5.66%). The relatively high rate of only IgG VCA antibody
      containing samples (480 cases, 26.41%) might indicate a previous EBV infection or
      the weakness of the cellular immunity of the given subject. Further studies are
      necessary to elucidate the problem.

PMID- 8532327
TI  - [Vaginal cancer in a woman with a family history of ovarian cancer].
AB  - The proband was referred to familial ovarian cancer surveillance because two of
      her sisters died of carcinoma of the ovary. Her third sister succumbed of
      cervical cancer and her brother had acute myeloblastic leukaemia. Her second
      brother is alive and healthy. None of her parents and their sibs suffered of
      malignant disease. The offspring of the proband's sibs are young and appear to be
      normal. During surveillance she developed a stage I vaginal cancer. Following
      preoperative brachytherapy she underwent a radical hysterectomy and bilateral
      salpingoophorectomy with pelvic lymphadenectomy, and she is free of disease
      during 2 years of follow-up. The authors are not aware of any similar case.

PMID- 8532328
TI  - [HELLP syndrome, an unusual form of pregnancy toxicosis].
AB  - The high maternal and perinatal morbidity and mortality associated with severe
      preeclampsia--eclampsia still have a remarkable significance. An unique form of
      preeclampsia--eclampsia is called HELLP syndrome which means hemolysis (H),
      elevated liver enzymes (EL), and low platelet count (LP). Authors demonstrate a
      patient treated in the intensive care unit and recovered completely from HELLP
      syndrome, and give a summary of the clinical findings and management principles
      of this life threatening complication. Authors emphasize the importance of the
      knowledge of HELLP syndrome for all physicians dealing with pregnant patients,
      considering that the fast established diagnosis and proper management can be life
      saving.

PMID- 8532329
TI  - [Centenary of the death of Louis Pasteur, founder of microbiology].

PMID- 8532330
TI  - [The physician-poet. The 200-year anniversary of the birth of John Keats].

PMID- 8532331
TI  - [The patient's right to make decisions, where does it start and where does it
      end?].

PMID- 8532332
TI  - [Anatomy and pathology of the rotator cuff].
AB  - In this contribution we stress the fact that not all rotator cuff tendinopathies
      are degenerative in nature. Moreover, we insist on a clear distinction between
      intrinsic and extrinsic tendinopathies. In a final note we point out that the
      impingement syndrome is not always due to a developmental or acquired spur of the
      anterior part of the acromion.

PMID- 8532333
TI  - [Clinical examination of the shoulder].
AB  - If the treatment of shoulder problems is to be successful, an accurate diagnosis
      is required. To achieve this, it is necessary to pay attention to some
      peculiarities of the shoulder joint. Because of the great importance of the soft
      tissues in dynamic and static stabilization, bony lesions will occur late when
      massive dysfunction of the shoulder has maybe just occurred. Imaging techniques
      as CT or X-ray will not give a diagnosis in the early phases. Therefore, an exact
      clinical evaluation with a history and assessment of motion and special muscle
      testing will permit an early diagnosis.

PMID- 8532334
TI  - [Double-contrast tomographic arthrography and double-contrast CT arthrography in
      rotator cuff lesions].
AB  - Arthrotomography is a good method for the evaluation of incomplete or complete
      tears of the supraspinatus tendon, the assessment of the size of tears and the
      quality of the nonruptured part. CT arthrography is useful in the evaluation of
      the subscapularis tendon and the labral-capsular components. It depends on the
      clinical symptoms and the result of primary arthrography whether both methods are
      performed in one session or not. Based on the experience of 1200
      arthro(tomo)graphy and axial CT arthrography examinations, the procedure and
      results in our institution are reported.

PMID- 8532335
TI  - [Magnetic resonance tomography in disorders of the rotator cuff].
AB  - Magnetic resonance imaging (MRI) has become a powerful diagnostic tool for the
      evaluation of the painful shoulder in general and of the diseased rotator cuff in
      particular. MRI evaluates cuff disease in terms of tendon morphology and
      pathologic signal alterations within diseased cuff tendons. Additionally, MRI
      displays important pathoanatomic changes of the coracoacromial arch which are
      predisposing factors for the development of shoulder impingement syndrome and
      cuff disease. The accuracy of MRI in diagnosing small rotator cuff tears and in
      assessing the integrity of the labral-ligamentous complex is improved by the
      intraarticular injection of a suitable contrast agent. In the preoperative
      assessment of patients with cuff disease, MR arthrography enhances the staging of
      the disease and allows a more confident exclusion of concomitant lesions of the
      shoulder joint.

PMID- 8532336
TI  - [Ultrasonography of the shoulder in subacromial syndromes with disorders and
      injuries of the rotator cuff].
AB  - Shoulder sonography was performed prospectively in 4172 patients with 4588
      shoulders affected with pathology of the subacromial space, among them 1227
      operated cases with 425 rotator cuff tears (292 total tears and 133 partial
      tears). A two-criterion model with formal as well as echogenic and dynamic
      criteria was used for the diagnosis of cuff tears. The overall sensitivity in
      diagnosing rotator cuff tears was 95.3% (97.3% in total tears and 91.0% in
      partial tears). False-negative results were found overall in 1.6% of cases.
      Overall accuracy for all defects was 94.9%. Involvement of the supraspinatus
      tendon was found in 95.8%, of the infraspinatus in 39.3% and of the subscapularis
      in 10.1%. In 33.6% of cases, involvement of the long head of biceps was found. It
      was clearly correlated with the size of the tears: 25.9% in isolated
      supraspinatus tears and 68.8% in three-tendon tears of subscapularis,
      supraspinatus and infraspinatus. Differentiation between fresh, traumatic tears
      and degenerative tears is possible by means of measuring retraction, determining
      the length of the distal cuff stump and by formal criteria of the stump
      configuration as well as by bursal criteria. Differentiation of old tears of
      suspected traumatic origin from those with degenerative causes is impossible.

PMID- 8532337
TI  - [Clarification of the concept humeroscapular periarthritis].
AB  - Shoulder pain may be due to various reasons. It is primarily produced by changes
      in the periarticular structures of the shoulder joint. The term "periarthritis
      humeroscapularis" (PHS), often used at diagnosis, is unsuitable however because
      it prevents differentiation of the various clinical pictures related to the
      anatomical structures. Among the anatomical structures concerned, above all the
      rotator cuff and here especially the suprasinatus muscle must be mentioned. Also
      the long biceps tendon and the shoulder joint capsule are, according to Welfling,
      locations of painful processes, not to forget the subacromial bursa. The
      pathology responsible for the clinical symptoms and signs is primarily produced
      by degenerative changes. They lead to tendopathy, as well as to tendon rupture,
      and also seem to be of importance in connection with calcifying tendopathy.
      Capsule shrinkage in shoulder stiffness can also be influenced by neighboring
      degenerative processes. This also applies to isolated bursitis. Today thorough
      clinical and radiological clarification makes a differentiated diagnosis possible
      so that the vague term "periarthritis humeroscapularis" can be dropped.

PMID- 8532338
TI  - [Open surgical therapy of the rotator cuff].
AB  - Almost 100 years have passed since the first report of rotator cuff repair in
      1898 by W. Muller. Even now new operative techniques are being developed. Various
      solutions for difficult extended forms of rotator cuff lesions are available
      besides the closed and semi-closed arthroscopic techniques. Anatomical
      reconstructive procedures such as local or distant tendon transfer compete with
      extra-anatomical procedures such as simple debridement, equatorial partial
      reconstruction or replacement with a delta flap. Hemiarthroplasty of the shoulder
      has proven to be more and more the treatment of choice in cases of inoperable
      rotator cuff defects with painful arthropathy. The euphoria caused by complicated
      reconstructive methods for massive tears has subsided due to an awareness that
      loss of function is inevitable in chronic degenerative tears with muscle atrophy.
      Reconstruction should be coordinated step by step with the operative procedure as
      well as adapted to the biological situation. It should definitely not be forced
      at any price using an algorithm for a rotator cuff tear operation, the best
      operative method must be selected by clinical, radiological and intraoperative
      criteria. The situation is completely different for an acute traumatic rotator
      cuff tear. Every effort should be made to perform early anatomic reconstruction
      in a young patient, as the function of the rotator cuff is of great importance in
      the working world. In contrast to degenerative changes of the rotator cuff
      tendon, large ruptures can be treated successfully if early immediate repair is
      performed. The long head of the biceps tendon plays a special role in combination
      with a rotator cuff tear. The concomitant lesions of the long head of biceps
      should not to be over-looked when repairing the rotator cuff tear. Until now, a
      special form of rotator cuff pathology has not received much attention--the so
      called interval lesion. It is the forerunner of the rotator cuff tear. The
      interval lesion is a partial tear of the ligamentous structures between the
      supraspinatus and subscapularis tendon and leads to damage of the long head of
      the biceps. The interval lesion can only be diagnosed by arthroscopy or open
      exploration of the rotator interval.

PMID- 8532339
TI  - [Arthroscopic treatment possibilities of the rotator cuff].
AB  - Many open operative procedures of the rotator cuff can be done arthroscopically,
      especially impingement lesions, partial and complete ruptures of the rotator
      cuff, osteoarthritis of the acromioclavicular joint and calcific tendinitis.

PMID- 8532340
TI  - [Conservative therapy and rehabilitation following surgery of the rotator cuff].
AB  - To achieve the best results after shoulder surgery, an optimal rehabilitation
      program is absolutely necessary. The physiotherapist must pay attention to some
      basic features such as biomechanics, functional anatomy and the current findings.
      The schedule of rehabilitation depends on the operative technique, the
      possibility of reconstruction of the rotator cuff and on the load capacity of the
      soft tissue. The goal of shoulder rehabilitation is the recovery of painless and
      normal shoulder function.

PMID- 8532341
TI  - Screening for primary open-angle glaucoma: a review.

PMID- 8532342
TI  - Non-contact tonometry.

PMID- 8532343
TI  - Indirect fundus biomicroscopy.
AB  - Non-contact fundus biomicroscopy permits a stereoscopic, highly magnified
      examination of the ocular fundus and vitreous with a large field of view. It
      should be considered the standard clinical technique for stereoscopic examination
      of the posterior pole of the eye. Lens selection is dependent upon personal
      preference and magnification requirements, although the latter is also dependent
      upon the optics of the slit lamp. For many, the new SuperField NC is the lens of
      choice as it gives the largest field of view, has superior optical quality and
      gives reasonable magnification, equivalent to that of the 90 D lens.

PMID- 8532344
TI  - Acquired immunodeficiency syndrome (AIDS) and the eye.

PMID- 8532345
TI  - [Difficulties in the aspiration cytodiagnosis of the neck tumors].
AB  - Since 1971 FNA is used at the ENT Department Medical Academy in Warsaw in the
      diagnosis of the neck and head tumors. This method was effective in 87.4% of
      cases. Among 382 biopsies of the neck tumors performed in 1980-1990, in which FNA
      results were compared with histopathology, in 12.6% of cases the false diagnosis
      was found. There were malignant primary tumors, cervical lymph nodes metastases,
      nonmalignant neck neoplasms, neck cysts and inflammations. The retrospective
      investigations of the smears allowed us to find out whether the false diagnosis
      depends on inappropriate interpretation of the smears or the diagnosis is really
      impossible to establish. The retrospective studies are very helpful for the
      better understanding of the malignant criteria and for the improvement of the
      results of the cytodiagnosis in the head and neck tumors.

PMID- 8532346
TI  - [The assessment of basement membrane in cancer of the floor of the mouth and
      larynx].
AB  - An immunohistochemical method using a monoclonal antibody to collagen type IV was
      employed to assess the basement membrane (BM) deposition in 36 cases of cancer of
      the floor of the mouth and in 32 cases of cancer of the larynx. The BM deposition
      was scored as extensive or limited, and compared to degree of histologic
      differentiation of tumor and to 3-year survival rate for patient and regional
      metastasis. There were 42 cases with extensive and 26 with limited BM deposition
      between cancer of the floor of the mouth and cancer of the larynx were found.
      Statistical analysis did not show a relationship between BM deposition of either
      cancer and the survival of patients or with regional metastasis, however a little
      better results was obtained for patients with extensive BM deposition. Poorly
      differentiated carcinoma of the floor of the mouth had a tendency to limited BM
      deposition.

PMID- 8532347
TI  - [Spirometric examinations at laryngectomized patients and healthy subjects].
AB  - Spirometric studies were conducted at 40 patients, divided into on basic group
      (20 laryngectomized men, aged 48-77 years) and comparative group (20 healthy men,
      aged 20-57 years). The results obtained showed that the mean value of airways
      resistance was about 5-times higher than at healthy subjects. The large
      resistance of airways influence for considerable decreasing of the maximum
      ventilation volume. Tracheitis and bronchitis chronic in cause of increase
      resistance of airways at laryngectomized patients and it can influence for
      quality and understanding of vicarious voice.

PMID- 8532348
TI  - [Laser resection of the vocal cord growth of the arytenoid cartilage in the
      treatment of contact ulcer].
AB  - 4 cases of larynx contact ulcer cured with the use of laser resection of vocal
      process of arytenoid cartilage were presented. Advantages of using laser been in
      microsurgery of larynx were discussed.

PMID- 8532349
TI  - [Jet ventilation as method of the general anesthesia in microsurgery of the
      larynx].
AB  - Usefulness of jet ventilation in carbon dioxide laser surgery of the larynx is
      presented. The authors describe the advantages of that method of general
      anesthesia in surgery of the larynx.

PMID- 8532350
TI  - [Mastoid pneumatization in otosclerosis].
AB  - With the use of planimetry, and ears lateral projection X-ray pictures, the size
      of temporal bones pneumatization surfaces was measured 88 ears with otosclerosis
      and 88 healthy ears were examined. The degree of pneumatization in the two groups
      was compared. Statistically significantly highly pneumatization was found in the
      group of ears with otosclerosis.

PMID- 8532352
TI  - [Round window reflex: valuable indices of the successful transmission
      reconstruction].
AB  - The author presents the round window reflex in tympanoplastic procedures. It is
      the most valuably index, which guarantee the successful reconstructions of the
      transmission system.

PMID- 8532351
TI  - [Osteoclastoma of temporal and zygomatic bone].
AB  - A twelve year boy was admitted to the Otolaryngological Clinic of the Medical
      Academy in Cracow with a paralysis of the peripheral facial nerve and a tumor on
      the right zygomatic arc. A CT investigation revealed an expansive process in the
      central fossa of the skull, which continuously passed into the squama of the
      temporal bone and the are of the zygomatic bone on the right side, causing a
      paralysis of the nerve VII. A neurosurgical intervention was carried out as well
      as a subsequent treatment by radiotherapy. A remission of the tumor was achieved.
      Osteoclastoma was diagnosed histologically.

PMID- 8532353
TI  - [The examination of vestibular system in patients with degenerative changes of
      the cervical spine].
AB  - Degenerative changes of the cervical spine often cause the pains and vertigo as
      well as pathological results of otoneurological tests. The aim of the study was
      to estimate the frequency of the symptoms occurrence in the group of 146
      patients, 63 male and 83 female, with degenerative changes of the cervical spine.
      Permanent or periodical headaches of various intensity occurred in 60% of the
      patients. Balance disturbances was observed in 74% of the patients, specially in
      women. In the cervical spine X-ray there were observed most frequently marginal
      degenerations with osteophytosis (16%), intervertebral disk narrowing (10%), and
      shallowing of the physiological lordosis (11%). In ENG examination, positional
      nystagmus (42-38%), gaze nystagmus (14-23%) were mainly recorded, with the eyes
      opened and closed. The eye-tracking pattern test was pathological in 57%.
      Optokinetic test results showed pathological records in 32% of the patients,
      unilateral weakness was observed in 22% and bilateral weakness in 17% of the
      patients. Observations mentioned above confirm frequent pathology and the
      necessity of early diagnosis and treatment of patients with degenerative changes
      of the cervical spine.

PMID- 8532354
TI  - [The influence of experimental hemispherectomy and hemicerebellectomy on the
      acquisition and retention of habituation in pigeon].
AB  - The subject of investigation was the analysis of the acquisition and retention of
      the vestibular habituation in pigeons after hemispherectomy or
      hemicerebellectomy. The habituation training was performed using rotatory test.
      The frequency of head nystagmus and postural reflexes were examined before and
      after acquisition of habituation and some days later, for evaluation of
      retention. Our results suggests that hemispherectomy does not inhibit acquisition
      of habituation but retention of this phenomenon is shorter at that time. The
      hemicerebellectomy makes impossible the vestibular habituation.

PMID- 8532355
TI  - [Gigantic osteoma of the maxillary sinus coexisting with retained tooth].
AB  - The case of gigantic osteoma co-existent with retained tooth of the maxillary
      sinus was introduced. Rareness of the osteomas location and co-existence with
      retained tooth was emphasized. The operation indications in osteomas of paranasal
      sinuses were analyzed. It was pointed out that fragmentation of the large
      osteomas during operation is often necessary.

PMID- 8532356
TI  - [Osteomas of frontal sinus].
AB  - In the years 1982-1992, 12 patients with frontal sinus osteoma were treated in
      the Department of Otolaryngology, Medical University in Cracow. The osteomas has
      been surgically removed by the brow incision. In the case of seven patients the
      tumor was removed as a whole but in five cases in parts because of their large
      size. In all patients the cosmetic result was satisfactory.

PMID- 8532357
TI  - [A case of lightning resulting in ear burn].
AB  - The authors described a rare case of 13 years old girl burnt by lightning. The
      burns of the skin of neck, perforation and destruction of the handle of malleus
      were stated. No internal ear injury was observed.

PMID- 8532358
TI  - [Postoperative maxillary cyst].
AB  - We presented the case report of a postoperative maxillary cyst, which developed
      26 years after the radical Caldwel-Luc procedure in the maxillary sinus. This is
      a rare case in nonoriental population but it has been described well in Japanese
      literature. Considering the size and damage found in clinical and radiological
      examination, we suspected a malignance lesion.

PMID- 8532359
TI  - [Branchiogenic carcinoma: cystic metastases from oropharyngeal primary neoplasm].
AB  - This study deals with an inconsistency concerning the existence of branchiogenic
      carcinoma. The data from the literature dealing with lateral cervical (branchial)
      cyst and branchiogenic carcinoma are presented. There are growing evidence that
      branchiogenic carcinoma in in fact cystic metastases from oropharyngeal
      carcinoma, most commonly tonsillar primary. The case of the patient with
      tonsillar carcinoma and cystic metastases to the neck, supporting this thesis is
      presented.

PMID- 8532360
TI  - [Diaphanoscopy (transillumination) of maxillary sinuses: a method too early
      forgotten?].
AB  - This paper is the work on history of diaphanoscopy (transillumination) of
      maxillary sinuses and other otolaryngological and abdomen organs. The aim of this
      paper is to present the transillumination of maxillary sinuses--an important
      method before X--rays invention. The contributions of various Polish physicians:
      Teodor Heryng, Ludwik Guranowski, Jozef Talko, Ludwik Neugebauer, Walery
      Jaworski, in the popularisation of diaphanoscopy are depicted.

PMID- 8532361
TI  - Professor P.C.C. Garnham (1901-1994).

PMID- 8532362
TI  - Plasmodium vinckei vinckei and P. yoelii nigeriensis: pattern of gametocyte
      production and development.
AB  - The morphological evolution and the periodicity of the gametocytes of two rodent
      malaria species were studied in the white mouse. Experiments with Plasmodium
      vinckei vinckei, a highly synchronous species, showed that the production of the
      sexual stages was periodic and was set by the specific rhythm of the asexual
      stages, i.e. the time of inoculation and the duration of the cycle in the blood.
      The duration of gametocytogenesis from merozoite to stage 0 was approximately 30
      hours, and from stage 0 to stage III, 6 hours. Plasmodium yoelii nigeriensis
      which normally develops asynchronously in the blood was synchronized by a Percoll
      glucose gradient fractionation. Although the duration of the asexual cycle was 18
      hours, gametocytogenesis from merozoite to stage 0 lasted 24 hours and 12 hours
      from stage 0 to stage III. Some degree of sequestration was observed in the young
      gametocytes.

PMID- 8532363
TI  - Contribution to a revision of the genus Plagiorchis (Trematoda: Digenea:
      Plagiorchiidae).

PMID- 8532364
TI  - Amoebicidal compounds from medicinal plants.
AB  - A series of the natural constituents with amoebicidal activity isolated from
      several medicinal plants is shown. A list of the medicinal plants potentially
      active as amoebicide and/or against dysentery also is demonstrated. The present
      data grouping of the natural compounds and medicinal plants can be an important
      source of information for the selection of research plant material by the
      investigators interested in the discovery of new biologically active compounds as
      amoebicide.

PMID- 8532365
TI  - Effect of an intraperitoneal injection with activated Hymenolepis nana and H.
      diminuta cysticercoids on homologous challenge.
AB  - The intraperitoneal injection of excysted-activated cysticercoids of Hymenolepis
      nana and H. diminuta stimulates a protective immunity in mice and rats against an
      oral homologous challenge with different levels of effectiveness. The immunizing
      dose reduced only worm growth in the natural host (i.e. H. nana/mouse and H.
      diminuta/rat models), while in the unnatural host (i.e. H. diminuta/mouse model)
      expulsion of the worms from the intestine was accelerated. In mice infected with
      H. nana the effect appeared about 20 days after injection, but a greater effect
      was found in both models 40 days later even at low dose (1 cysticercoid). In rats
      the effect appeared 40 days after injection when a large inoculum (50 or 100
      cysticercoids) was used. The induced immunity was slow in developing and only
      partially effective: this was probably related to host difficulties in processing
      somatic worm antigens, or to the slow production of metabolites by the worms in
      the peritoneal cavity.

PMID- 8532366
TI  - The morphology of Laemobothrion (Laemobothrion) maximum (Phthiraptera:
      Laemobothriidae).
AB  - Adult specimens of Laemobothrion (L.) maximum (Scopoli, 1763), a buzzard louse
      species, were studied using scanning electron microscopy and paying special
      attention to sensitive structures, mainly those located on the head, mouthparts,
      abdomen and legs. Data on shape and size of palpl and antennal sensilla, as well
      as post-spiracular ones, were obtained. Some modifications of the mouthparts were
      observed.

PMID- 8532367
TI  - [Leishmania-macrophage interactions: role of cytokines and molecules co-involved
      in killing].
AB  - In this review we have summarized the main data concerning Leishmania-macrophage
      interactions, with particular emphasis on receptors involved in adhesion,
      activating or deactivating cytokines and toxic molecules responsible for parasite
      killing. At present it is also known that a different T helper (Th)1- or Th2-cell
      response may be critical for the outcome of Leishmania infection in human and in
      murine models. Therefore, we have mentioned the recent studies on cytokines, such
      as IL-2, which are able to cause the switch from a Th2, disease-promoting immune
      response, to a Th1, protective response. In fact, in the light of these findings,
      these molecules may be used in the future for immunotherapeutical or
      immunoprophylactic purposes.

PMID- 8532368
TI  - Onset of resistance to light Hymenolepis nana infection in mice of different
      strains.
AB  - Rapidity in onset of resistance against Hymenolepis nana egg infection after a
      light primary infection was studied in low and high responder mice challenged at
      different time intervals. A very rapid acquisition of protection was observed in
      C57 and a delayed response in C3H mice. In both cases the effect of resistance on
      weight or worm number was related to the time of challenge infection, suggesting
      a "race against time" involving host response and parasite development, the
      outcome varying according to host genetic background.

PMID- 8532369
TI  - Cyathocephalus truncatus (Cestoda: Spathebothridea) in its intermediate host
      Echinogammarus stammeri (Amphipoda) from the River Brenta, northern Italy.
AB  - A study was carried out on the occurrence of the tapeworm Cyathocephalus
      truncatus (Pallas, 1781) (Cestoda: Spathebothridea) in its intermediate host, the
      amphipod Echinogammarus stammeri, in the River Brenta. A total of 18,860 E.
      stammeri was examined from July 1990 to June 1994; only 25 of them (prevalence
      0.13%) were infected with tapeworm larvae (intensity of infection 1 larva/host).
      Co-occurrence of C. truncatus larvae with the larva of the acanthocephalan
      Pomphorhynchus laevis (Muller, 1776) was recorded in 15 amphipods. Tapeworms were
      localized in the anterior portion of each amphipod's hemocoel, in intimate
      contact with E. stammeri internal organs such as the alimentary canal, and
      frequently induced its displacement. No differences in integumental pigmentation
      were noticed between infected and non-infected amphipods, and some infected E.
      stammeri females were ovigerous.

PMID- 8532370
TI  - Recent acquisitions on tick and tick-borne disease resistance in N'dama (Bos
      taurus) and Gobra zebu (Bos indicus) cattle.
AB  - The use of disease resistant breeds is recognised as an economically realistic
      alternative to acaricide application and drug administration in tick and tick
      borne disease control schemes. Although resistance is mainly associated with zebu
      (Bos indicus) breeds, studies carried out in The Gambia show a higher resistance
      to ticks and tick-borne diseases in N'dama (Bos taurus) than in Gobra (B.
      indicus) cattle. Tick resistance in N'dama breed appears to be effective against
      those species with long hypostome, such as Amblyomma variegatum and Hyalomma spp.
      The possible mechanisms involved are discussed. Further investigations are
      identified to assess the economic value of tick and tick-borne disease resistance
      in the N'dama breed.

PMID- 8532371
TI  - [Bovine setariasis in Friuli Venezia Giulia].
AB  - Blood samples from 407 bovines of "Azienda Marianis", a farm in Friuli Venezia
      Giulia, Italy, were examined for microfilariae; 143 (35.1%) were positive. A
      survey in other 23 farms of dairy cattle from 6 Communes of the Province of Udine
      revealed a prevalence of 11.28%. The prevalence was significantly correlated with
      the age of animals; in cow was lower than in young animals. Blood microfilariae
      (210) and adult females (15) were identified as Setaria labiatopapillosa.

PMID- 8532372
TI  - [Human sub-conjunctival dirofilariasis: a probable case seen in France by Amatus
      Lusitanus in the 16th century].
AB  - In the book Curationum medicinalium Centuria septima (1566) of the Portuguese
      physician Amatus Lusitanus (1511-1568) a curious clinical case is reported
      concerning a 3 year-old girl from Limoux (Aude, Southern France) affected by
      ocular filariasis with the worm spontaneously emerging from the eye. On the basis
      of the description and localisation of the parasite, and of the locality where it
      was observed, the nematode might be identified as Dirofilaria repens, the
      causative agent of canine and human dirofilariasis in the Old World. The case was
      reported by Ulysse Aldrovandi (1522-1605) in his book De animalibus insectis
      (1602) with a commentary. According to the text of Lusitanus and to Aldrovandi's
      commentary, it would appear that both authors had observed additional similar
      cases, the former referring to ocular and the latter to mammal localisations. If
      this identification is correct, the zoonosis may have existed in Southern France
      and Italy for 400 years and the report by Lusitanus may represent the first human
      case of dirofilariasis published in the world.

PMID- 8532373
TI  - Forcipomyia (Pterobosca) paludis (Macfie, 1936) (Diptera, Ceratopogonidae) on
      adult dragonflies (Odonata) in Sardinia, Italy.
AB  - Ceratopogonid midges, referred to Forcipomyia paludis, were recorded from five
      dragonfly species in Sardinia, Italy. All ceratopogonids were females and almost
      all were in the last phase of the gonotrophic cycle (gravid females). Although a
      parasitic association cannot be excluded, no evidence was obtained of the midge
      biting activity, neither by direct observation nor indirectly, by detecting the
      expected lesions on the host cuticle. The attachment to dragonflies of F. paludis
      (perhaps an autogenous species) might fit well with the hypothesis of a phoretic
      association which would favour the long range dispersal of the gravid females.

PMID- 8532374
TI  - Lungworm infection in laboratory dogs reared in Italy.
AB  - Lungworms, Filaroides hirthi, were observed in histological lung sections in 4
      out of 96 beagle dogs (4.2%) reared for experimental studies in Italy. Infected
      animals were 2 males and 2 females, 8 months old, with no clinical signs, while
      in another case a granulomatous lesion, possibly transmitted by this lungworm,
      was found. Histopathological changes of lung induced by F. hirthi can mimic some
      drug-induced and neoplastic lesions, and therefore to cause misunderstanding
      during interpretation of results of toxicological studies. This is the first
      report of F. hirthi infection of laboratory dogs reared in Italy.

PMID- 8532375
TI  - [Inhibitors of protein-tyrosine kinases: pharmacological perspectives?].

PMID- 8532376
TI  - Effect of prolactin, rIFN-gamma or rTNF-alpha in murine toxoplasmosis.
AB  - Mice lethally infected with T. gondii and treated with prolactin (PRL),
      recombinant interferon gamma (rIFN-gamma) or recombinant tumour necrosis factor
      (rTNF-alpha) were protected against death, as compared to untreated controls. The
      protective effect of PRL (0.5-2 mg/kg/twice daily for 12 days) was dose dependent
      and statistically significant (P < 0.001). The survival was 50% or 40% in mice
      that received doses of 1 x 10(4) U of rIFN-gamma or 4 x 10(4) U of rTNF-alpha at 
      2, 0, +2 days before and after infection (P < 0.0001). An increase of time to
      death, up to 60 days after challenge, and of survival rate (50% up to 70%) were
      observed in animals treated with PRL in combination with either rTNF-alpha or
      rIFN-gamma, compared to those that received treatments with the same therapeutic
      agents alone; however the differences were not statistically significant. In
      addition, a slight synergistic effect on brain cyst formation, with lower number
      of Toxoplasma cysts, was observed in mice treated with PRL plus TNF-alpha (P <
      0.01), compared with animals that received rTNF-alpha alone (P < 0.05). These
      data suggest that PRL can regulate in vivo endogenous TNF-alpha production in the
      cytokine cascade. We conclude that prolactin may play an important role in
      modulating the host's immune defence against T. gondii opportunistic infection.

PMID- 8532377
TI  - [Use of the Bactec TB 460 method for the bacteriological diagnosis of
      tuberculosis. Results of a multicenter study].
AB  - Isolation of Mycobacteria on Loewenstein-Jensen medium lasts many weeks. The use
      of Radiometric method (Bactec TB 460) reduces the delays. Results of 79,064
      cultures are reported from a multicentric study associating 16 laboratories. The
      average was 4.8% of positivity and 2.51% of contamination. The comparison of the
      results with conventional method previously obtained shows that radiometric
      method is more sensitive and contaminations are less numerous. Concerning
      hemocultures the Bactec method is very usefull. Among 11,277 tests performed 907
      were positive (8.04%). Mycobacterium avium was identified in 89% of the cases.
      Identification test utilizes Biochemical and NAP tests, but also more and more
      Nucleic probes. The antibiotic sensitivity is performed in five days. The mean
      delay of analysis is about 25 days, lessening by half the conventional method
      delays. Nevertheless, Bactec method has the following inconveniences: syringe
      inoculation, use of radiolabelled products, expensive cost.

PMID- 8532378
TI  - [Evaluation of an ELISA technique for the serodiagnosis of legionnaires'
      disease].
AB  - The presence of anti-Legionella antibodies was studied comparatively in 81 sera
      with a commercially available ELISA kit (containing serogroups 1 to 6 as
      antigens) and the indirect immunofluorescence assay (IFA) with serogroup 1. The
      values obtained with the ELISA method were converted into immunofluorescence
      titers by using standard sera. Results of both methods were concordant in 83% of
      the sera when a cutoff value of 1/128 was used, and in 88% of the sera when the
      cutoff value was 1/128 for IFA and 1/256 for ELISA. In 6 other patients infected
      by serogroups other than 1, antibodies were detected in 5 cases with ELISA and in
      none with IFA.

PMID- 8532379
TI  - Use of digoxigenin-labeled RNA probe to test hepatitis A virus antiviral drugs.
AB  - A nucleic acid hybridization assay was used to evaluate inhibitory activity of
      antiviral compounds against hepatitis A virus (HAV) in cell culture and compared
      to radioimmunoassay by analysis of variance procedure. The 5' genomic end of the
      HM-175 strain was used as digoxigenin-labeled RNA probe. Dot-blot examination
      showed a reduction of detectable HAV RNA in infected cells when treated with
      amphotericin B. An antiviral dose-effect was shown by statistical analysis of
      densitometric measures of hybridization signals. Comparison between molecular
      hybridization assay and radioimmunoassay by analysis of variance procedure showed
      the equivalence of both methods. Data previously obtained on selected drugs by
      antigen and infectious titres determinations were confirmed by hybridization
      assay and make possible digoxigenin-labeled RNA probe use to measure an antiviral
      dose-effect for screening of hepatitis A antiviral compounds.

PMID- 8532380
TI  - [Cardiac involvement in fetal parvovirus B19 infection].
AB  - The review of 15 cases of cardiac involvement demonstrate the cardiac tropism of
      the human parvovirus B19. Ten of these cases were collected from fetuses during
      second trimester of maternal-fetal infections. In situ hybridisation detects
      viral DNA sequences in the nucleus of infected myoblasts. Myocarditis is the most
      frequent histological damage. Cardiac failure, secondary to myocarditis, may
      occur in the absence of fetal anaemia. When the fetus is deeply anaemic, like
      usually in cases of hydrops, damages of the cardiac tissues might hamper the
      reactional increase of cardiac output; therefore, they might account for the poor
      prognosis of parvovirus B19 fetal hydrops in the second trimester of pregnancy,
      despite transfusional therapy attempts in the third trimester.

PMID- 8532381
TI  - [Structure of chromatin. 2: levels of organization of DNA in the nucleus. Highly
      organized structures].
AB  - In the interphase nucleus, the 30 nm fiber, whose characteristics were discussed
      in the first part of this review, is condensed 10-15 fold to form loops or
      domains of chromatin with a DNA packing ratio of 600. In the metaphase
      chromosomes, the packing ratio is 12000. The existence of loops in the interphase
      nucleus has been suggested by experiments from electronic microscopy,
      sedimentation and nuclease digestion. These loops of 20-200Kb are attached at
      their bases to a non-histone protein network, that is the nuclear matrix or
      scaffold whose major component is the topoisomerase II. There is disagreement
      regarding the arrangement of the loops in metaphase chromosomes and several
      models have been proposed. Six of these models are presented. A number of data
      suggest that the sequences of attachment (SARs/MARs) define functional units
      containing related genes. Thus, the compartmentation of the genome in
      topographically independent domains might ensure the fidelity of epigenetic
      transmission of the chromatin structure, and it might help to control gene
      expression. In the interphase nucleus, the chromosomes coexist with other domains
      involved in major nuclear functions such as transcription, replication or post
      transcriptional modifications and whose compartmentation is not always evident.

PMID- 8532382
TI  - [Effect of benzquercin on the connective tissue of lathyritic mice. Optic and
      electron microscopic study].
AB  - Vascular pathology is characterized by important alterations of some vessel
      macromolecular constituents, such as fibrous proteins, collagens and elastin. The
      purpose of our study was to establish the activity of benzquercin treatment on
      such alterations of the vascular wall. As experimental model we used lathyrism
      induced in mice by chronic administration of beta-amino-propionitril (beta-APN).
      This compound prevents crosslink-formation in elastin and collagen and provokes a
      disorganization of the structure and an alteration of the physiological functions
      of the vascular wall. The connective tissue of the skin is also impaired
      simultaneously with that of the blood vessels. We compared by optical and
      transmission electron microscopy the morphological structure of the aorta and the
      skin of 3 groups of mice: a normal control group, an other which only received
      the beta-APN alone and a third one which received the beta-APN and the
      benzquercin treatment. The second group, injected with beta-APN without
      treatment, showed important alterations of the structure of the aorta as well as
      of the skin. Both fibrous proteins, collagen and elastin were concerned by these
      alterations, the consequence of which was an increase of the permeability of the
      aorta wall demonstrated with the horse-radish peroxydase as a tracer. The third
      group, injected with beta-APN and treated with the benzquercin, showed much less
      morphological disorders than the untreated group and the vascular permeability
      was also close to normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532383
TI  - [Role of glycosoaminoglycans in venous disease. Mode of action of some flavonoid
      drugs].
AB  - Varicose vein walls differ from normal venous walls by an important loss of their
      collagen content and an increase of their glycosaminoglycan content, essentially
      of hyaluronan. The decrease in fibrous protein content can be attributed to
      increased proteolytic (collagenolytic) activity as well as to free radicals.
      Glycosaminoglycan increase reflects a disregulation of the normal program of
      matrix biosynthesis by the cells of varicose vein wall, essentially smooth muscle
      cells. Some flavonoid drugs are capable of correcting these deviations by
      decreasing proteolytic attack on fibrous proteins and the accumulation of
      proteoglycans and hyaluronan. These effects, due to interactions between
      flavonoid drugs and the cells and fibrous proteins of the venous wall differ
      according to the nature of such drugs. A hypothesis is proposed to explain these
      differences in the intensity of action of flavonoid drugs with apparently closely
      related structures, based on the conformation of these drugs and their
      interaction with the triple helical structure of collagen fibers as well as with
      the cell membranes.

PMID- 8532384
TI  - [Critical analysis of tests for rapid detection of Staphylococcus aureus,
      Pastorex Staph plus, Slidex Staph-kit and Staph aureus in clinical isolates].
AB  - One hundred and seventy three clinical isolates of mannitol fermenter
      staphylococci, including 120 S. aureus (38% methicillin resistant) and 53
      coagulase negative staphylococci were assayed for direct detection of S. aureus
      on colonies. Three new rapid slide agglutination tests were compared: Pastorex
      Staph Plus, Slidex Staph Kit and Staph aureus. Each one detects fibrinogen
      receptor and protein A. According to the addition of monoclonal antibodies,
      Pastorex Staph plus is intended to detect capsular antigens 5 and 8, and Slidex
      Staph kit to detect a surface glycopolysaccharide. Sensitivities of these tests
      were equal, Pastorex Staph plus 95%, Slidex Staph kit 94.2%, Staph aureus 95.8%.
      Among meticillin-resistant S. aureus, sensitivities reached 91.3%, 87% and 91.3%
      respectively. Specificities over coagulase negative staphylococci which gave
      conclusive results were 92.5%, 90.2% and 90.4% respectively. The validity of
      these results was checked over 100 staphylococcal primary isolates of medical
      samples in April 1994. Over 62 S. aureus (29% methicillin-resistant) Pastorex
      Staph plus and Staph aureus sensitivities were 96.8% and 98.4% respectively and
      specificities were 94.6% and 91.9% over 37 coagulase negative staphylococci which
      gave conclusive results. Staph aureus test sensitivity is at least equivalent to
      second generation tests as well in primary cultures as in subcultures The best
      specifity is achieved with Pastorex Staph plus, which contains latex particles
      without red blood cells.

PMID- 8532385
TI  - A comparison of coronary arteries from Japanese and NZ subjects.
AB  - This paper describes a comparison of the anterior descending branch of the left
      coronary artery from 198 Japanese subjects of ages less than 60 yrs, with 301 New
      Zealand individuals of similar ages. The object of the study was to determine
      whether there were structural differences present which could be partially
      responsible for the low incidence of atherosclerosis in Japanese as well as the
      known low blood lipid levels. It was found that the internal elastic lamina of
      Japanese coronary arteries was less well formed at birth than that of NZ
      subjects. Intimal thickening was greater in Japanese coronary arteries from birth
      to the end of the first decade, but increased less rapidly with age, and was only
      about half as great as that of NZ vessels in the older age groups. The thickened
      intima of Japanese arteries was more uniform round the circumference of the
      vessel, the luminal surface was better formed with more stainable elastin present
      subjacent to the endothelial cells, and there was less evidence of mural
      thrombosis. NZ arteries showed pronounced eccentricity of the intima, more
      extensive lipid deposits, a poorly defined luminal surface, and frequent evidence
      of mural thrombosis.

PMID- 8532386
TI  - Differences between standard and high-sensitivity immunohistology in tissue
      sections--comparison of immunoperoxidase staining methods using computerized
      video image analysis techniques.
AB  - High-sensitivity immunoperoxidase labelling can be achieved using heavy metal
      enhancement of the di-amino (DAB) reaction product. For example nickel chloride
      combined with DAB improves the sensitivity of the method approximately 7-10 fold.
      This allows detection of approximately 100-200 molecules on cell surfaces. This
      has an obvious advantage over standard non-enhanced DAB methods which detect 1000
      2000 molecules under similar conditions. This study compares standard and nickel
      enhanced DAB immunoperoxidase staining of cells in tissue sections using video
      image analysis (VIA) measurement techniques. VIA is an objective method of
      evaluation of immunoperoxidase staining of separated cells and for immunostained
      cells in tissue sections. Nickel enhancement of the DAB reaction product reveals
      more positively stained cells, with higher contrast over background, giving
      superior qualities for VIA analysis providing continuous, reproducible, and
      objective data for statistical analysis.

PMID- 8532387
TI  - Aortitis with dissection complicating systemic lupus erythematosus.
AB  - A 31 yr old female under treatment for systemic lupus erythematosus complained of
      episodes of atypical chest pain radiating to the back. Subsequently she suddenly
      collapsed and died. Post mortem revealed a well-defined, localized area of non
      giant cell aortitis extending from the supra-aortic ridge of the aortic valve to
      the ligamentum arteriosum. Active arteritis with fibrinoid necrosis and
      obliterative endarteritis of vasa vasorum had resulted in multiple infarcts of
      differing ages with associated inflammation and disruption of the aortic wall,
      culminating in aortic dissection and cardiac tamponade.

PMID- 8532388
TI  - Immunohistochemical detection of oncogene proteins and neuroendocrine
      differentiation in different stages of prostate cancer.
AB  - The progression of prostatic adenocarcinoma from localized disease to metastatic
      carcinoma appears to be a multi-step sequence. The expression of common
      oncogenes/oncosuppressor genes and the mediating effect of neuroendocrine tumor
      cells may play a role in this progression. The expression of the more frequently
      investigated oncogenes/oncosuppressor genes (p53, c-myc, c-erbB-2, bcl-2) and the
      presence of neuroendocrine cells were assessed in prostatic cancer tissue from
      patients with localized and metastatic cancer. These oncogenes/oncosuppressor
      genes were evaluated according to tumor stage and grade and their relationship to
      one another. Grade was not related to any of the oncogene markers or to the
      presence of neuroendocrine cells. Advancing stage was associated with a
      significant increase in p53 expression, while other markers remained constant in
      all stages. Neuroendocrine cells, p53, c-myc, c-erbB-2 and bcl-2 were rarely co
      expressed at any stage of prostate cancer.

PMID- 8532389
TI  - Progression from Goodpasture's disease to membranous glomerulonephritis.
AB  - An unusual case of a patient with Goodpasture's disease presenting with
      hemoptysis, severe iron deficiency anemia and microscopic hematuria and
      proteinuria is described. Both circulating and tissue anti-glomerular basement
      membrane (GBM) antibodies were present, and renal function remained normal
      throughout. Immunosuppressive therapy was given for subclinical pulmonary
      hemorrhage with successful resolution of anemia and disappearance of the
      circulating anti-GBM antibody. Nine months after presentation he developed
      nephrotic range proteinuria and a repeat renal biopsy revealed membranous
      glomerulonephritis with no evidence of his original disease. Both the
      Goodpasture's associated HLA-DR2 and the membranous associated HLA-DR3 class II
      antigens were present. The association of antibody mediated and immune complex
      glomerulonephritis is discussed. The simultaneous presence of HLA-DR2 and HLA-DR3
      may predispose to this association.

PMID- 8532390
TI  - Renal glomerular lesions in unselected patients with cirrhosis undergoing
      orthotopic liver transplantation.
AB  - Renal biopsies were obtained from 23 patients at the time of orthotopic liver
      transplantation. Twelve biopsies showed minor glomerular abnormalities, 2
      exhibited IgA nephropathy and one showed mesangiocapillary glomerulonephritis
      type I. The remaining 8 patients had glomerular lesions diagnosed as hepatic
      glomerulosclerosis (HGS). Immunofluorescence, available in 6 of the 8 biopsies
      with HGS, revealed granular deposits of immunoglobulins and complement in
      glomerular capillary walls and/or the mesangium. IgA was seen in 5 biopsies with
      HGS, but the staining for this protein was no more intense than that for the
      other immunoglobulins in 4 of these. Electron microscopy in HGS revealed partial
      mesangial interposition, hypertophy of mesangial and endothelial cells, granular
      material in a widened subendothelial space, slender projections of endothelial
      cytoplasm extending into the subendothelial space, and clusters of vesicles in
      the mesangium and glomerular capillary walls. These ultrastructural abnormalities
      have not hitherto been reported as a group of associated pathological changes.
      The renal biopsies were obtained from patients with advanced hepatic disease not
      selected because of urinary abnormalities or renal dysfunction. The frequency of
      lesions in this group of patients therefore probably reflects the true incidence
      of glomerular lesions in cirrhosis and related conditions. Progressive decline in
      renal function was not observed in any patient during follow up which ranged from
      11 days to 55 mths.

PMID- 8532391
TI  - Tobacco smoke induced lung granulomas and tumors: association with pulmonary
      Langerhans cells.
AB  - The density of zinc-iodide-osmium (ZIO) positive pulmonary Langerhans dendritic
      cells (LC) was increased about 20-fold in mice after passive exposure to tobacco
      smoke. This was associated with pulmonary changes consistent with the cigarette
      smoking-related clinical syndrome in humans, pulmonary Langerhans cell
      granulomatosis. The major feature was an interstitial peribronchial granuloma.
      The cellular infiltrate of the granuloma (lymphocytes, plasma cells, eosinophils,
      clusters of large histiocyte-like cells and macrophages) extended into the
      adjacent alveolar septum forming a star-shaped lesion. The histiocyte-like cells
      were large with pale acidophilic cytoplasm and many ill-defined short dendrites
      extending from the cell membrane. Bronchial epithelial metaplasia also developed.
      The interstitial changes were followed by the development of proliferative
      alveolar and bronchial lesions in 2 mice. The zinc-iodide-osmium positive cells
      were consistent with la positive pulmonary dendritic cells and their
      ultrastructure was similar to that of pulmonary Langerhans cells. After ceasing
      exposure to tobacco smoke the density of pulmonary Langerhans cells returned to
      that of the control level; interstitial granulomatous lesions disappeared, but
      the bronchial epithelial metaplasia did not reverse. Tobacco smoke exposure of
      mice produces interstitial granulomatous inflammation similar to Langerhans cell
      granulomatosis in humans. The elevated level of pulmonary Langerhans cells
      implicate these cells in the pathogenesis of these lesions.

PMID- 8532392
TI  - Evans' syndrome, myelofibrosis and systemic lupus erythematosus: role of
      procollagens in myelofibrosis.
AB  - We describe an 18 yr old female with systemic lupus erythematosus presenting with
      Evans' syndrome (autoimmune hemolytic anemia and immune thrombocytopenia) and
      dense myelofibrosis. Her clinical course and response to treatment were monitored
      with regular blood counts, serial measurements of serum procollagen I and III and
      periodic bone marrow examinations. This report brings to 9 the number of well
      documented cases of systemic lupus erythematosis and myelofibrosis in the
      literature; we discuss the pathogenesis and management of patients with this
      apparently rare disorder, with particular reference to the role of serum
      procollagen measurements as markers of myelofibrosis.

PMID- 8532393
TI  - Selection and implementation of a laboratory computer system.
AB  - The process of selection of a pathology computer system has become increasingly
      complex as there are an increasing number of facilities that must be provided and
      stringent performance requirements under heavy computing loads from both human
      users and machine inputs. Furthermore, the continuing advances in software and
      hardware technology provide more options and innovative new ways of tackling
      problems. These factors taken together pose a difficult and complex set of
      decisions and choices for the system analyst and designer. The selection process
      followed by the Microbiology Department at Heidelberg Repatriation Hospital
      included examination of existing systems, development of a functional
      specification followed by a formal tender process. The successful tenderer was
      then selected using predefined evaluation criteria. The successful tenderer was a
      software development company that developed and supplied a system based on a
      distributed network using a SUN computer as the main processor. The software was
      written using Informix running on the UNIX operating system. This represents one
      of the first microbiology systems developed using a commercial relational
      database and fourth generation language. The advantages of this approach are
      discussed.

PMID- 8532394
TI  - Death by hanging in Western Australia.
AB  - We present a review of the circumstances and medical findings of 280 fatalities
      due to hanging in Western Australia (WA) during the 5 yr period 1988-1992. Two
      hundred and forty one (241) of the cases were examined prospectively; the
      completed Coroner's files of a further 39 cases, from rural WA, were examined
      retrospectively. Most of the 280 deaths were in males (88%), and most were in the
      age range of 15-35 yrs (56%). Seven cases occurred in children aged 15 or less.
      There was one homicide, 14 cases thought to be accidental, and 261 suicides; in 4
      cases the manner of death could not be determined. In one-third of the cases
      there was a medical history of a psychiatric condition. The majority occurred in
      or around the decedent's home (71%). The most commonly used ligature was a rope
      (59%). Alcohol was the most commonly detected drug following post mortem analysis
      (30%). In WA then, there is one hanging death every 6.5 days, the majority being
      suicides, in men of young adult age, typically occurring in or around the home.

PMID- 8532395
TI  - A report of accidental ethylene glycol ingestion in 2 siblings.
AB  - We describe a case of 2 siblings aged 2 1/2 and 3 1/2 yrs accidentally poisoned
      by ethylene glycol ingestion. We found estimating the level of ethylene glycol in
      plasma by calculation of osmolar gap too insensitive to be of value and advocate
      the availability of a specific method. In our study only one of the 2 children
      had a toxic level of ethylene glycol but assay by conventional assay and by
      proton magnetic resonance spectroscopy (1HMRS) of toxic metabolites viz
      glycolate, glyoxylate and oxalate showed both to be excreting grossly elevated
      levels. This indicates the desirability of assaying the toxic metabolites of the
      glycol as well as the parent compound in assessing ingestions.

PMID- 8532396
TI  - Alpha-fetoprotein-producing adenocarcinoma of the sigmoid colon with possible
      hepatoid differentiation.
AB  - A patient with adenocarcinoma of the sigmoid colon producing alpha-fetoprotein
      (AFP) is described. Hepatoid differentiation is suggested by the morphological
      appearance and production of hepatic-type AFP. The possible histogenesis of such
      a tumor is discussed.

PMID- 8532397
TI  - Ductal carcinoma of male breast with prominent lipid-rich component.
AB  - We report a case of mammary duct carcinoma with a prominent lipid-rich, sebaceous
      like component, occurring in a 55 yr old white male. The patient presented with a
      painless, subareolar left breast mass and the diagnosis of malignancy was made by
      fine needle aspiration. Subsequent modified radical mastectomy revealed an
      infiltrating and in situ ductal carcinoma with dermal invasion and numerous
      vacuolated sebaceous-like tumor cells, positive for neutral lipid by Oil Red O
      stain. We propose that this case represents an unusual variant of lipid-secreting
      breast carcinoma. To the best of our knowledge, this subtype of mammary carcinoma
      is unprecedented in male breast.

PMID- 8532398
TI  - Pancreatic pseudotumor arising in association with Sjogren's syndrome.
AB  - A case is presented of an elderly female who was found by imaging to have an
      enlarged pancreas with narrowed distal common bile duct, thought to be
      neoplastic. Resection revealed an inflammatory and fibrosing process of the
      pancreas, suggestive of autoimmune disease. Subsequently she developed dry mouth,
      enlarged salivary glands, and an enlarged lacrimal gland with typical histology
      of Sjogren's syndrome. Pathological review of the contralateral lacrimal gland
      excised 20 years earlier showed similar histology. This case is a rare, but not
      unique, example of pancreatic pseudotumor associated with Sjogren's syndrome. The
      increasing use of sophisticated abdominal imaging may result in an increased
      detection of such pseudotumors. Failure to recognize their real nature can lead
      to inappropriate surgery.

PMID- 8532399
TI  - Harlequin ichthyosis--a case report.
AB  - The Harlequin infant represents the most severe form of nonbullous ichthyosis.
      Although the clinical features of infants with Harlequin ichthyosis are generally
      similar, histological, ultrastructural, and biochemical analyses have not shown
      consistent findings. An unexpected case of Harlequin ichthyosis in a female
      infant born at 35 wks gestation is presented. Light microscopic and
      ultrastructural investigations of skin biopsies are detailed. The presence of
      extracellular lipid material in the stratum corneum has not been described in the
      previously reported cases of Harlequin ichthyosis.

PMID- 8532400
TI  - DNA flow cytometric analysis of abortions. A simple method for detection of
      triploidy and tetraploidy in the trophoblastic cells.
AB  - By flow cytometric analysis of nuclear DNA content it is possible to demonstrate
      the cellular clones that have a quantity of DNA higher or lower in comparison
      with that of diploid nuclei. The possibility of measuring DNA ploidy by flow
      cytometry provides a simple way to asses triploidy and tetraploidy in placental
      tissue. In this investigation, are reported the results of the DNA analysis in a
      series of 540 consecutive spontaneous abortions or suction curettage material
      obtained after intrauterine death, which was detected by ultrasound examination.
      At microscopy 351 (65.0%) cases showed feature of normal placentas, 147 (27.2%)
      of hydropic abortus, 27 (5.0%) of partial hydatidiform mole and 15 (2.8%) of
      complete hydatidiform mole. DNA flow cytometric analysis showed triploidy in 38
      cases (7.0%) and tetraploidy in 12 cases (2.2%). Comparing microscopic feature
      and ploidy, 12 normal placental specimens were triploid, 6 were tetraploid. Nine
      hydropic abortuses had a triploid DNA content, 5 a tetraploid DNA content. In the
      group of partial hydatidiform moles triploidy has been found in 14 cases, whereas
      tetraploidy in one case and diploidy in 12 cases. Twelve complete hydatidiform
      moles showed a diploid DNA content and 3 a triploid one. The incidence of
      poliploid pregnancies has been higher among young patients. In most cases the
      poliploid pregnancy was the first pregnancy of the patient. DNA flow cytometric
      analysis is a simple and useful mean to state etiology of many spontaneous
      abortion, even when histology is negative. This analysis must be associated with
      morphology in this field.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532401
TI  - [Proliferative activity of ependymomas. (Quantitative analysis of the expression
      of Ki67 and AgNOR)].
AB  - One of the problems connected to the anatomo-clinical evaluation of ependymomas
      consist in the difficulty of precisely grading these neoplasms and of making a
      prognosis. Traditional histopathologic procedures have proven themselves
      unsuitable to solve these biological problems of neoplastic growth: their
      solution requires the identification and responsiveness of molecules that are
      part of cellular kinetic processes such as antigen Ki67 and the granules of AgNOR
      as indexes of the rDNA transcriptional activity. With the aim of contributing to
      the knowledge of ependymomas' grading, the Authors performed qualitative and
      quantitative assays on 35 cases of benign ependymomas (by means of an image
      analyzer) using the nuclear antigen Ki67 and the AgNOR nucleolar areas. The
      results thus obtained allow to draw the following conclusions: 1) The biological
      validity of the labeling of antigen Ki67 and the quantification of argentophilic
      granules in the NOR areas has once more been confirmed. 2) The expressiveness and
      biological significance of antigen Ki67 is finer than what can be derived from
      the count of AgNOR granules. 3) The level of diagnostic reliability for the
      differentiation between and the corresponding malignant forms is optimal; such a
      level falls considerably when one wishes to grade levels of benignity of
      malignity. 4) Such drawbacks are likely to be due to the action of heterogeneous
      factors which are often unrelated to the neoplasm, such as poor oxygenation,
      blood stream alterations, necrosis, phlogosis, nutritional conditions of the cell
      populations etc.

PMID- 8532402
TI  - [Neuromalaria: neuropathological study of 3 cases and review of the literature].
AB  - Human Cerebral Malaria (HCM) is an encephalopathy which occurs in some patients
      infected with P. falciparum (PF). Besides people in the endemic tropical
      subtropical zones there is a numerically smaller group of non immune visitors or
      returning from which are at risk for disease. The histological classical
      hallmarks of HCM are sequestration of PF-infected erythrocytes in vessels,
      cerebral oedema, petechial hemorrhages "ring hemorrhages" and so-called Durk's
      granulomas. Even though the histological and clinical picture are described for
      more than a century, some aspects of the pathogenesis of this disease remain
      obscure. We report the neuropathological findings of three European cases of HCM
      consisting of a slight diffuse oedema both of cortex and white matter and
      numerous capillaries filled with parasitized erythrocytes (PRBC). The
      pathogenetic aspects especially as to concern the sequestration of cerebral
      vessels are reviewed particularly in regard to the recent immunohistochemical
      evidence of "intercellular adhesion molecules" (ICAM-1, E-selectin etc.) as
      ligands to endothelial cells for PRBC.

PMID- 8532403
TI  - [2 fatal cases of acute myeloid leukemia (M3, M4) during pregnancy].
AB  - Two cases of unexpected post-partum death of women with acute leukemia are
      described. In the first case (1st pregnancy) the diagnosis (acute promyelocytic
      leukemia: M3) was performed one week before delivery and death occurred 3 days
      later, because of hemorrhagic and renal DIC complication. Since one month before
      hospitalization, laboratory exams indicated a serious hematological pathology and
      no further exams were carried out by the physicians, elements of professional
      fault were recognized in them, considering that because of the diagnostic
      omission it was impossible to make an early diagnosis and thus perform to
      specific therapy, adopted only in the terminal phase. This specific therapy is
      able to determine remission from most cases of acute promyelocytic leukemia. In
      the second case (2nd pregnancy) the diagnosis (acute myelomonocytic leukemia: M4)
      was performed only postmortem because, during the whole pregnancy, no signs of
      disease were evident. After a few hours from the spontaneous delivery, death
      occurred as a result of an intractable + hemorrhagic syndrome caused by primary
      hyperfibrinolysis and repeated episodes of cardiac arrest, without possibility of
      recognizing it. The medical procedures for this case, both throughout pregnancy
      and terminal phases, appeared free of censure.

PMID- 8532404
TI  - Pre-operative interleukin-2 immunotherapy induces eosinophilic infiltration in
      colorectal neoplastic stroma.
AB  - Interleukin-2 (IL-2) may induce peripheral eosinophilia and this phenomenon is
      related with response to IL-2 immunotherapy in patients with metastatic renal
      cell carcinoma. In previous experiences is reported that preoperative course with
      IL-2 may reverse the surgery-induced immunosuppression. This study's objective is
      to evaluate the histological changes of inflammatory infiltration in tumour
      stroma, in patients pretreated with IL-2 immunotherapy. 7 patients admitted to
      our surgical department with resectable recurrent colorectal cancer were treated
      with pre-operative course of IL-2; the tissue samples were analyzed for
      eosinophilic and inflammatory infiltration and compared with the samples obtained
      in the primary operation, performed without immunotherapy. In all patients were
      observed an increase of eosinophilic infiltration in tumour tissue. The mean
      increase were 200%, with high statistical significance (p < 0.0001). IL-2 pre
      operative immunotherapy is able to change the interaction between host and
      tumour, by modifying the histological inflammatory infiltration in colorectal
      cancer tissue.

PMID- 8532405
TI  - [Human dirofilariasis in southern Italy. III. The Molise region].
AB  - A case of subcutaneous human dirofilariasis associated with Dirofilaria repens in
      the arm of a 9-year-old child resident in Campobasso is described. It is the
      first report of the nematode in the Molise region. Blood samples taken from dogs
      in the same region, confirmed the presence of D. repens microfilariae in the
      natural reservoir, few km from the clinical case.

PMID- 8532406
TI  - [Clear-cell sarcoma of the tendons and aponeuroses. Immunohistochemical study of
      2 cases].
AB  - Two cases of clear cell sarcoma of tendons and aponeuroses are reported. Clinical
      setting, protracted course, and light microscopic appearance were in a agreement
      with the original description. In the first case the tumor required differential
      diagnosis from metastatic malignant melanoma because of the lack of the overlying
      skin and of the epithelial histological pattern. In the second case diagnosis was
      not too difficult; the tumor consisted of nest or fascicles of uniform pale
      staining cells intermingled by inconspicuous multinucleated giant cells with
      peripherally placed nuclei. The histologic features and immunohistochemistry are
      also discussed.

PMID- 8532407
TI  - [Urinary cytology of transitional-cell carcinoma].
AB  - The authors report on their experience about urinary cytology in 1991. They
      studied 100 patients with cytology and histology, carried by cystoscopy and cold
      mapping biopsy, trying to have notice about cytological value and proficiency.

PMID- 8532408
TI  - [A rare mesenchymal tumor of the larynx . Case report and anatomo-clinical
      features].
AB  - Laryngeal chondrosarcoma is an uncommon mesenchymal tumor and in the world
      literature only 220 cases have been reported. We report in this retrospective
      examination three cases which age ranged from 54 to 65 years; one was a man and
      two were women. Two of the tumors arose in the thyroid cartilage, one in the
      cricoid cartilage. All the cases corresponded to low-grade, well-differentiated
      chondrosarcomas of the hyaline type (grade I) and two of the patients were alive
      and free from recurrence or metastasis after 6 and 12 years. One had a recurrence
      5 years later with a superior histologic grade (grade II) and died 6 months after
      laryngectomy from metastatic disease. The AA. discusses the importance of
      assessing location, size, state of the resection borders, histologic grade and
      recurrence for the correct evaluation of the neoplasia, for therapeutic and
      prognostic purposes.

PMID- 8532409
TI  - [Primary angiosarcoma of the thyroid. Presentation of a case (epithelioid type)
      and nosological problems].
AB  - There is a great deal of confusion in the literature as to whether or not true
      angiosarcomas of the thyroid exist or whether these are all anaplastic carcinomas
      of the thyroid which have an angiosarcomatoid appearance. Due to the fact that
      undifferentiated carcinomas of this organ can strikingly resemble various
      sarcomas it is recommended that great care should be taken prior to qualify as an
      angiosarcoma a malignant thyroid tumor. A lot of viewpoints have been expressed
      so far in literature concerning this theme, and they can be summarized as
      follows. On one side and not admitting the existence of angiosarcoma in this
      location there are opinions which think of it as a "variant" of undifferentiated
      carcinoma (a pure carcinoma with a pseudovascular pattern or a carcinoma with an
      intermingled non-neoplastic reactive vascular component), or as a neoplasm in
      transition from epithelial to endothelial differentiation ("mesenchymal
      neometaplasia"), or as a carcinoma with aberrant expression of endothelial
      markers, or as a carcinoma with a non-specific uptake of endothelial
      antigens(e.g. from serum in case of F-VIII R-Ag positivity). On the other side
      there are opinions in favor of the existence of such an entity, based upon light
      microscopy features coupled with immunocytochemical results (endothelial antigens
      expression without or with cytokeratins expression) and with the possible support
      of electron microscopy. Anyway ultrastructural findings of specific markers
      (Weibel-Palade bodies, pericellular basal lamina, tight junctions,
      subplasmalemmal pinocytotic vesicles) according to some authors are not a
      prerequisite: so poorly differentiated neoplasma can fail to show those
      histogenetic markers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532410
TI  - [Primary amyloid tumor of the breast. Case report and review of the literature].
AB  - Along with an introductory summary concerning practically with all types of
      amyloidoses the authors report on a case of a primary amyloid tumor in a female
      patient, which resulted the eight after a computer-assisted literature search.
      Amyloid deposits in the breast represent an extremely rare event, which has been
      described in three clinical settings, in patients with reactive or secondary
      amyloidosis, in patients with immunocytic amyloidosis (this term including both
      the so-called primary form and the myeloma-associated form), and finally even in
      patients who are well and otherwise asymptomatic. Amyloid deposits in the breast
      can occur in the course of a systemic involvement as well as in form of a
      localized or organ-limited disease ("amyloid tumor"). Further the latter form is
      qualified as a "secondary amyloid tumor" (in those patients affected by certain
      neoplastic diseases, plasmacellular or non plasmacellular, or by a chronic
      infectious-inflammatory-dysreactive process) or as a " primary amyloid tumor" in
      those who are found free of any disease and of any other amyloid deposits. The
      case the authors report on deals with a lady who was admitted due to a breast
      lump which mammographically was thought suspicious for malignancy by virtue of a
      cluster of variously sized microcalcifications. At histology the lesion was
      diagnosed as an amyloid deposit on special stains and disclosed of the AL type
      with Congo red stain on sections previously treated with KMn04, according to
      standard methods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532411
TI  - Metastatic renal cell carcinoma presenting as a parotid tumor: a case report.
AB  - Renal cell carcinoma rarely metastasize to the parotid gland; only 16 cases have
      been reported in the literature. We describe a 68-year-old man presenting with a
      1-year history of a painless swelling on the right parotid gland. A partial
      parotidectomy was performed. The histological examination revealed a clear cell
      neoplasm, and the tumour cells were periodic acid-Schiff positive and diastase
      labile. The differential diagnosis involved the primary clear cell tumors of the
      parotid gland and metastasis of malignant extrasalivary neoplasms. Histochemical
      end immunohistochemical studies for vimentin, keratins and CEA are consistent
      with a metastatic renal cell carcinoma.

PMID- 8532412
TI  - [Primary microcytoma of the larynx. Case report, ultrastructural study and review
      of the literature].
AB  - Oat cell carcinoma of the larynx is a rare tumor. A throughout search of the
      literature revealed only 80 cases; the first case in literature was reported by
      Olofsson in 1972. The tumor often presents in the sixth and seventh decades of
      life and appears to be highly aggressive and metastases develop early. We have
      had the opportunity to study ultrastructurally a small cell carcinoma of oat cell
      type arising in the larynx.

PMID- 8532413
TI  - [Granular cell tumor of the rectum: description of a case with unusual
      histological features].
AB  - The localization of granular cell tumor to the rectum is rare. We describe a case
      characterized by areas with spindle cell pattern, pleomorphic cells with
      acidophilic granular cytoplasm, nuclear variations and absence of mitoses.
      Diagnosis has been confirmed by immunohistochemical study. After 22-month follow
      up the patient does not show evidence of recurrence or metastases.

PMID- 8532414
TI  - [Multilocular cysts of the kidney in the adult].
AB  - Multilocular cyst of the adult kidney is a benign lesion of uncertain
      pathogenesis. We report a case studied by immunohistochemical techniques. A
      malformative histogenesis is suggested.

PMID- 8532415
TI  - Nodular renal blastoma in kidney with multicystic dysplasia. Report of a case.
AB  - The clinico-pathologic association of nodular renal blastema, multicystic kidney
      and obstructive uropathy has been recently identified. We report on a female
      patient diagnosed as having unilater multicystic dysplasia by prenatal
      ultrasonography. The patient was nephrectomized at the age of 6 1/2 months.
      Examination of the resected kidney revealed multiple unilocular cysts in the
      cortex and hypoplasia of the homolateral ureter; histological study confirmed the
      presence of multiple cysts limited to the renal cortex, and revealed, among them,
      multiple cortical metanephric blastema cells islands. Our case supports a
      relationship between nodular renal blastema, cortical cysts and obstructive
      uropathy; ureter hypoplasia could cause intraluminal back pressure, with
      consequent abnormal development of the ampullae, normally endowed in nephronic
      anlagens induction, cystic tubular ectasia and persistence of nodular renal
      blastema. The peripheral location of renal nodular blastema and cysts supports a
      late error in nephrogenesis, at the time of formation of the last generation of
      nephrons.

PMID- 8532416
TI  - [Pleomorphic storiform malignant fibrohistiocytoma of the larynx. Case report and
      anatomo-clinical considerations].
AB  - We have studied a rare case of malignant fibrous histiocytoma of the larynx, of
      the storiform-pleomorphic variety, diagnosed already as fibrosarcoma on two
      bioptical examinations performed to distance of a month the one from the other.
      The second biopsy showed an histological grade superior to the first and the
      patient came to death for lung metastasis two years later. The
      immunohistochemical study confirmed the mesenchimal origin of the tumor,
      excluding the presence of epithelial elements. Given the aggressive course, for
      the application of the different therapeutic protocols and for prognostic
      purposes it is underlined the need to make an attentive differential diagnosis
      also on histogenetic bases as regards the other mesenchimal and epithelial
      malignancies that they can simulate from near the histologic appearance. It
      proved very important, to such end, the immunohistochemical investigation, if
      correctly interpreted.

PMID- 8532417
TI  - [Spindle-cell carcinoma of the larynx].

PMID- 8532418
TI  - [Xanthelasma of the sigmo-rectal wall].
AB  - Xanthelasma is a benign localized collection of lipid-laden histiocytes, that is
      usually idiopathic and immunohistochemical studies confirmed the histiocytic
      nature of the proliferation. It is here reported a case in the sigma-rectum, with
      a review of the recent literature on the argument. Although it is a well
      recognized entity already described in various organs, its occurrence in the wall
      of the sigma-rectal channel is at all uncommon. It is suggested that the lesion
      could be referred to a local immunological disorder, with a cell mediated
      mechanism.

PMID- 8532419
TI  - [Rhombencephalic tissue in an ovarian teratoma with cerebellar foliation and
      maturation of the postnatal type].
AB  - In a women 32 years old, primipara with pregnancy to term hesitated caesarian
      birth, a cystic mature teratoma was found on both ovaries. While the content of
      the cyst of the left ovary appeared deprived of descriptive interest, in that of
      the right ovary, beyond to locks of hair, tegumental tissue, sebaceous matter and
      to a bone in miniature, they were structures relatively well diversified
      belonging to the nervous central system and particularly to the rhombencephalus
      (hindbrain). At the microscopic examination it was well recognizable a cerebellar
      structure with a microfolic configuration and with histological maturity of the
      postnatal type, identified for her neuronal depletion of the layer of the
      external granules and for the advanced myelination. It is advanced the hypothesis
      of a correlation between the maturation of the teratoma and the coexisting term
      pregnancy.

PMID- 8532420
TI  - Epidemiology and prevention of meningococcal disease.

PMID- 8532421
TI  - Repeatedly positive human immunodeficiency virus type 1 DNA polymerase chain
      reaction in human immunodeficiency virus-exposed seroreverting infants.
AB  - Three human immunodeficiency virus type 1 (HIV-1)-exposed children who had
      repeatedly positive DNA polymerase chain reaction (PCR) tests for HIV in > or = 5
      samples before seroreversion to HIV-negative status are reported. The children
      belong to a cohort of 210 infants who were born to HIV-infected mothers and were
      tested at intervals of 1 to 3 months by HIV viral culture, PCR, and p24 antigen;
      only the PCR was positive in > or = 5 samples in the children reported here.
      Their clinical features were indistinguishable from other seroreverters. All
      three children had a transient drop in CD4:CD8 ratio to < 1.0. The transiently
      positive DNA PCR in HIV-exposed infants may indicate either that HIV infection
      was eliminated by a strong host immune response or that infection was caused by
      an attenuated/defective strain of virus.

PMID- 8532422
TI  - Barriers to prevention of perinatal group B streptococcal disease.
AB  - During 1992 the American College of Obstetricians and Gynecologists (ACOG) and
      the American Academy of Pediatrics (AAP) issued statements on prevention of group
      B streptococcal (GBS) disease. To assess prevention practices and identify
      barriers to preventing GBS disease, we surveyed obstetricians, family
      practitioners and general practitioners in Georgia during 1993. A standard
      questionnaire was mailed to 1190 clinicians in August and to nonresponders again
      in September. Of 436 (38%) physicians who responded, 192 (44%) provided obstetric
      care. Among these 192 obstetric care providers, 121 (63%) screened patients for
      GBS carriage antenatally. The most frequently cited reasons for not screening
      were "no clear guidelines" and "not cost-effective" (52 and 39%, respectively).
      Clinicians who screened patients were significantly more likely to believe that
      screening was cost-effective (P = 0.05). Of obstetric care providers who
      screened, only 9% obtained specimens using culture sites recommended by ACOG or
      AAP. Although most clinicians were aware that antenatal antibiotic treatment of
      carriers does not prevent perinatal GBS disease, 64% of those who screened
      reported that they gave oral antibiotics when carriage was detected during
      pregnancy. Of clinicians who reported using obstetric risk factors to guide
      prophylaxis choices, < 15% reported using intrapartum antibiotics for the
      conditions identified in the ACOG and AAP statements as those that suggest the
      need for prophylaxis when screening is not performed. Many Georgia obstetric care
      providers do not use effective practices to prevent perinatal GBS disease.
      Education on appropriate culture methods, obstetric risk factors and the cost
      effectiveness of prevention strategies might lead to more effective preventive
      practices.

PMID- 8532423
TI  - Influence of malignancy on the pharmacokinetics of vancomycin in infants and
      children.
AB  - This prospective, controlled study evaluates the influence of malignancy on the
      pharmacokinetics and dosage requirements of vancomycin in 33 infants and children
      with cancer (age 5.72 +/- 4.11 years, mean +/- SD) compared with 31 patients
      without cancer (age 4.18 +/- 5.10 years) using a two-compartment Bayesian
      pharmacokinetic program. Patients in the malignancy group required a vancomycin
      dosage regimen of 71.5 +/- 13.9 mg/kg/day to attain a mean peak serum vancomycin
      concentration (SVC) of 22.38 +/- 4.54 mg/liter and a mean trough SVC of 6.84 +/-
      2.78 mg/liter. Patients without cancer in the control group required a mean
      vancomycin dosage regimen of 50.2 +/- 13.0 mg/kg/day to attain a mean peak SVC of
      21.70 +/- 6.70 mg/liter and a mean trough SVC of 8.05 +/- 3.01 mg/liter.
      Comparative analysis of pharmacokinetic data revealed an increase in vancomycin
      clearance (0.149 +/- 0.028 liter/hour/kg) in the malignancy group as compared
      with that (0.114 +/- 0.031 liter/hour/kg) in the control group. There were no
      significant differences with respect to the mean values of volume of distribution
      between two groups (0.638 +/- 0.079 liter/kg vs. 0.618 +/- 0.102 liter/kg).
      Analysis of the predictive performance of the Bayesian program indicated that
      final sets of peak and trough SVCs were predicted with minimal bias and accurate
      precision in both study groups. This study showed that the presence of malignancy
      in infants and children increased vancomycin clearance resulting in larger dosage
      requirements.

PMID- 8532424
TI  - Respiratory carriage of Kingella kingae among healthy children.
AB  - The role of Kingella kingae as an invasive pathogen of young children is being
      increasingly recognized, but the niche of the organism in the respiratory tract
      and its prevalence in the normal flora of children remain unknown. To investigate
      these two aspects throat and nasopharyngeal cultures were obtained every 2 weeks
      from two cohorts of children, ages 6 to 42 months on enrollment, attending a day
      care center in southern Israel. To determine the age-related prevalence of K.
      kingae, throat cultures were obtained from children ages 6 months to 14 years
      hospitalized for elective surgery who had not received antibiotics during the
      previous 30 days and from healthy infants younger than 6 months attending a well
      baby-care clinic for routine vaccinations. During an 11-month follow-up 109 of
      624 (27.5%) throat cultures but none of the nasopharyngeal cultures obtained from
      48 day-care center attendees grew K. kingae. The monthly prevalence of K. kingae
      ranged from 6.1 to 34.6% with December and April peaks. Overall 35 of 48 (72.9%)
      children had at least one positive culture for the organism. Among the 27
      children who had > or = 2 positive cultures, continuous and intermittent patterns
      of carriage were observed. None of the colonized children experienced an invasive
      K. kingae infection. The prevalence of pharyngeal carriage among surgical
      patients was 8.0%, and the organism was not isolated from any of the infants
      younger than 6 months attending the well-baby-care clinic.

PMID- 8532425
TI  - Childhood tuberculosis in Alabama: epidemiology of disease and indicators of
      program effectiveness, 1983 to 1993.
AB  - An 11-year review of childhood tuberculosis in Alabama was made in order to
      define indicators of program effectiveness in interrupting community
      transmission. Minority (nonwhite) children, 96% of whom were black, had the
      highest risk of disease (odds ratio, 5.5; 95% confidence interval, 3.9, 7.7). Of
      171 cases, 71% (n = 122) occurred in blacks and 2% (n = 3) occurred in Asian
      Pacific islanders. Age 0 to 4 years (107 of 171) compared with age 5 to 14 years
      (64 of 171) was an additional risk factor for the development of tuberculosis
      (odds ratio, 3.4; 95% confidence interval 2.5, 4.7)), whereas gender was not.
      Males accounted for 49% of cases (83 of 171). During the period 1983 to 1993
      there was no trend of increasing or decreasing numbers among child cases (trend
      test P = 0.94) despite significant changes by year. The purified protein
      derivative test had a 9% (8 of 89) false negative rate and was significantly more
      likely to be negative in children younger than 1 year (4 of 12 vs. 4 of 77; P =
      0.01). During the 2-year interval 1992 to 1993, 19% of cases were thought to be
      preventable. We believe that the PPD skin test is useful and an improved contact
      investigation is essential to preventing childhood tuberculosis. Miniepidemics of
      transmission of tuberculosis from adults to a large group of children partially
      explain the observed disease pattern.

PMID- 8532426
TI  - Weight, height and human immunodeficiency virus infection in young children of
      infected mothers. The European Collaborative Study.
AB  - In a longitudinal study of weight and height over the first 4 years of life, 123
      human immunodeficiency virus (HIV)-infected and 654 uninfected children of
      similar social background were compared. By 3 months of age there was a 400-g
      (8.0%) difference in weight and an 0.8-cm (1.3%) difference in height between
      infected and uninfected children. After age 1 year the differences stabilized and
      infected children were, on average, approximately 6% less heavy and 2% shorter
      than uninfected children. Most of the weight difference was explained by
      differences in height, particularly after age 1 year. Although statistically
      significant the difference between infected and uninfected children was small.
      Weight and height measurements were not useful indicators of infection. Before 6
      months of age differences in weight velocity could not be explained by HIV
      related morbidity and might have been related to a primary HIV infection. At
      older ages growth failure associated with HIV infection could be attributed to
      secondary HIV-related morbidity.

PMID- 8532427
TI  - Respiratory virus infections during anticancer treatment in children.
AB  - To evaluate the occurrence and clinical significance of respiratory virus
      infections in children during anticancer treatment, we studied 75 consecutive
      episodes of febrile infection in 32 children during 17 months. Viral antigen
      detection for 7 respiratory viruses, viral culture for rhinoviruses and enzyme
      immunoassay serology were used. Evidence for respiratory virus infection was
      found in 28 (37%) cases. Rhinovirus was the most common virus detected in 13
      (17%) episodes. The other etiologic agents were respiratory syncytial virus (6
      episodes), parainfluenza virus type 3 (5 episodes), adenovirus (4 episodes),
      influenza A virus (3 episodes), and influenza B virus (1 episode). Respiratory
      virus infections were diagnosed as often in leukopenic as in non-leukopenic
      patients (37% vs. 38%). In 4 cases bacteremic infection was diagnosed. We found
      no difference in serum C-reactive protein values when episodes positive for
      respiratory viruses were compared with virus-negative episodes. Our observations
      show that respiratory virus infections are common in febrile children receiving
      anticancer treatment. Diagnostic tests for respiratory viruses should be used
      more often in evaluation of fever in these patients.

PMID- 8532428
TI  - Prophylactic use of antibiotics and reduced case fatality in measles infection.

PMID- 8532429
TI  - Recurrent meningitis: the search for the dermoid or epidermoid tumor.

PMID- 8532430
TI  - Meningeal inflammation in neonatal gram-negative bacteremia.

PMID- 8532431
TI  - Balamuthia mandrillaris: a newly recognized agent for amebic meningoencephalitis.

PMID- 8532432
TI  - Detection of bacteremia in young infants: is 48 hours adequate?

PMID- 8532433
TI  - Long-term magnetic resonance survey of cartilage damage in leukemic children
      treated with fluoroquinolones.

PMID- 8532434
TI  - Polymerase chain reaction is more sensitive than standard cytologic stains in
      detecting Pneumocystis carinii in bronchoalveolar lavages from human
      immunodeficiency virus type 1-infected infants and children with pneumonia.

PMID- 8532435
TI  - Intradermal hepatitis B vaccination: five-year follow-up.

PMID- 8532436
TI  - Single dose and steady state pharmacokinetics of intravenous acyclovir in
      children undergoing bone marrow and liver transplant.

PMID- 8532437
TI  - Neonatal skin as a reservoir of Malassezia species.

PMID- 8532438
TI  - Brucellosis presenting with cough.

PMID- 8532439
TI  - Primary sternal osteomyelitis.

PMID- 8532440
TI  - Tuberculous inguinal lymphadenitis.

PMID- 8532441
TI  - Hydrocephalus in mumps meningoencephalitis: case report.

PMID- 8532442
TI  - Fever, abdominal pain and an intracranial mass.

PMID- 8532443
TI  - Sinusitis caused by Mycobacterium avium-intracellulare in a patient with human
      immunodeficiency virus.

PMID- 8532444
TI  - Influence of concurrent tasks on gait: a dual-task approach.
AB  - We studied the effect of concurrent tasks on motor control of gait with dual-task
      methodology. Ten healthy subjects were instructed to perform different cognitive
      and motor tasks during gait on a conductive walkway. Footswitch signals were
      recorded and stride time and double-support time were calculated. It was assumed
      that the former reflects gait-patterning mechanisms and the latter relates to
      balance control. Statistical analysis showed an increase in double-support time
      when a memory-retention task (digit-span) and a fine motor task (buttoning) were
      executed simultaneously during gait. During gait performance of the cognitive
      task declined compared to baseline conditions. Attentional demand of concurrent
      cognitive and motor tasks appeared to force subjects to modulate their gait
      strategy to ensure control of balance. Stride time was consistent across task
      conditions except when subjects performed fast finger-tapping during gait. Then
      all but one subject showed a decrease in stride time and an increase in stride
      frequency that was repeatable on retest. Since different rhythmic movements are
      likely to share common neurobiological networks, we assumed that the modulation
      of stride-frequency was due to structural interference.

PMID- 8532445
TI  - Sensory interaction and descriptions of fabric hand.
AB  - 82 subjects who viewed and felt fabrics (sensory interaction group) used
      different categories of terms to describe fabric hand than did 38 subjects who
      only felt the fabrics. Therefore, the methods used to measure fabric hand that
      isolate the senses may not accurately assess the way in which subjects describe
      fabric hand in nonlaboratory settings.

PMID- 8532446
TI  - Negative self-perception and components of stress in Canadian, British, and Hong
      Kong adolescents.
AB  - Responses to a 68-item Adolescent Stress Scale of 14- to 16-yr.-olds in Canada (n
      = 369), Britain (n = 217), and Hong Kong (n = 349) were compared. Four common
      subscales identified by principal component analysis emerged in the three
      samples. Scores on subscales (Relationship Problems, Abuse at Home, Scholastic
      and Career Problems, and Loneliness and Social Isolation) were significantly
      correlated for both sexes with negative self-esteem scores in the three national
      groups. Differences in stress between cultures were explicable in terms of known
      cultural differences.

PMID- 8532447
TI  - Influences of age at onset of blindness on Braille reading performances with left
      and right hands.
AB  - Several previous studies suggest that early sensory deprivation produces a
      changed organisation of the cerebral cortex. This study compared the effects of
      early and late total blindness on a Braille reading task. This task is intended
      to induce a superiority of the left hand rather than the right because of the
      particular role played by the right hemisphere in Braille decoding. 38 strongly
      right-handed adults, accustomed to daily bimanual Braille reading, were tested.
      21 subjects were born blind and 17 became blind during childhood before learning
      to read. Analysis indicated that previous visual experience can, under certain
      conditions, play a modulating role in manual superiority in Braille reading.

PMID- 8532448
TI  - Pain in infancy: individual differences.
AB  - Two patterns of reactions to painful medical procedures were found in infancy,
      i.e., continuous and interval patterns. Also, infants often in a good mood in
      everyday life (as reported by their mothers) showed pain more briefly after blood
      sampling, while infants often in a bad mood in everyday life showed pain longer.

PMID- 8532449
TI  - Variations in several mechanical parameters associated with elbow flexion during
      practice under different load criteria.
AB  - The purpose of this study was to analyze variations in the accuracy of the moment
      produced by the elbow flexors during feedback-assisted acquisition of a motor
      skill. The task consisted of minimizing the error around three criterional
      levels: 20%, 30%, or 50% of the maximal isokinetic concentric moment of these
      muscles measured at 90 degrees/sec. Healthy women, aged 22 to 30 years, were
      divided into three groups (nA = 6, nB = 6, nC = 4) corresponding to the above
      criteria. They were asked to perform 10 sets of 10 right-elbow flexions per day
      over a period of three consecutive days. The results indicated a significant
      difference among the groups mainly in terms of overshooting (Group A) or
      undershooting (Group C) the criterion. On the other hand, Group B subjects
      performed optimally as indicated both by a significant convergence to the
      criterion (30%) and a comparatively small number of repetitions required for
      achievements. These findings demonstrate the existence of an optimal performance
      point which is located at about 30% of the maximal isokinetic concentric moment.

PMID- 8532450
TI  - Type A-B behavior and nightmare types among college students.
AB  - To consider the relationships among Type A-B behavior, gender, and specific types
      of nightmares, 780 university undergraduates were tested with Glass' version of
      the Jenkins Activity Survey and the Spadafora and Hunt Dream Types Survey which
      included the critical nightmares (fantastic nightmares, posttraumatic nightmares,
      and night terrors). Relative to students classified as Type B, those classified
      as Type A were significantly more likely to report experiencing certain types of
      nightmares, i.e., fantastic and posttraumatic nightmares. We also observed that
      women reported significantly greater frequencies of all types of nightmares than
      men. Possible reasons for these differences were discussed.

PMID- 8532451
TI  - Differences in academic achievement as a function of scores on hemisphericity.
AB  - The subjects were 55 undergraduates enrolled in psychology classes and classified
      by their scores on the Human Information Processing Survey as having preferences
      of left hemisphericity (n = 17), right (n = 19), and integrated hemisphericity
      found between left- and right-hemisphericity groups with the left-hemisphericity
      group obtaining higher course grades.

PMID- 8532452
TI  - Relationship of body image and creative dance movement.
AB  - Findings supporting the proposition that dance movement improves a person's body
      image have been contradictory. Previous work focussed on styles such as ballet,
      jazz, and modern dance but it is arguable that creative dance movement, with its
      less structured approach and absence of predetermined performance standards, will
      have a positive influence on body image. This study examine scores on the
      Multidimensional Body-Self Relations Questionnaire of 112 women between 18 and 69
      years who had been actively participating in creative dance movement courses for
      periods ranging from two weeks to 16.5 years. Subjects experienced in creative
      dance movement were more satisfied with their appearance, fitness, and body parts
      than subjects with less than five years of experience. Differences in evaluation
      of health were not clearly established. Given this analysis and the potential for
      wide-spread clinical use of creative dance movement with people having body-image
      disturbances, empirical research on the relationship between creative dance
      movement and body image is warranted.

PMID- 8532453
TI  - Learning an imposed timing in a sequential arm movement.
AB  - The possibility of learning an imposed timing in a sequential arm movement was
      investigated as such observations could have important implications for learning
      in sport. The experimental task was performed by 26 women and 19 men on a
      vertical digitizer and required a movement made of four segments, different in
      both length and direction. To impose a timing very different from a spontaneous
      one, the spontaneous temporal organization on this task had first to be
      characterized. Then, during the learning, visual and auditory information about
      the imposed timing was given to subjects on each trial. Analysis showed that
      subjects accurately learned the imposed timing; moreover, the learning was a
      discontinuous process. Finally, it was obvious that the learned timing could be
      transferred to a reversed spatial pattern.

PMID- 8532454
TI  - Effects of vibrating movement on geometrical illusions and illusory contours.
AB  - Both geometrical illusions and illusory contours were facilitated by slight
      vibration. This suggests that they are produced by similar mechanisms.

PMID- 8532455
TI  - On the focal distance of the eye during sighting in pistol shooting.
AB  - We measured the focal distance and pupil diameter on the eyes of 11 marksmen
      sighting a pistol target at 23 m distance. Both upon the focal distance and pupil
      diameter of the subjects, we estimated the point at which they were looking
      during sighting. Calculation based on depth of field which can be divided from
      the pupil diameter of 4.5 mm suggested that the subjects were looking at the
      foresight of the pistol approximately 80 cm in front of the eye during sighting.

PMID- 8532456
TI  - The use of next-of-kin in assessing handedness.
AB  - The present study administered a 15-item handedness questionnaire to 129 college
      students and their next-of-kin. This questionnaire was similar to the Edinburgh
      Handedness Inventory, except that a 7-point scale was used instead of a 2-choice
      scale. Test-retest reliability was evaluated with a second administration of the
      handedness questionnaire to each subject. Analysis showed a high test-retest
      reliability for all items and a high correlation between subjects and next-of-kin
      responding for most items. However, some items on the Edinburgh Handedness
      Inventory showed much higher correlations than others when comparing subject and
      next-of-kin responding. The contribution of these data is that subjects'
      handedness can be accurately estimated from next-of-kin responses if a subset of
      these questionnaire items are used.

PMID- 8532457
TI  - Brain-emitted event-related potentials recorded during rapid decision-making may
      be useful in monitoring the neuropathogenesis of the human immunodeficiency virus
      (HIV).
AB  - Event-related potentials recorded from HIV-infected patients while they detected
      oddball targets during rapid delivery of dual sequences of tones showed the
      complete absence of the late, 300-msec., positive (P300) component, suggesting an
      alteration in the neuronal activity underlying cognitive processing.

PMID- 8532458
TI  - Stopwatch for measuring thumb-movement time.
AB  - The feasibility of using a stopwatch to measure thumb-movement time was examined.
      The measurements, which did not differ significantly between the nondominant and
      dominant hands, possessed high intrasession reliability. The measurements
      discriminated between 19 apparently healthy individuals and 19 older patients
      with a variety of diagnoses.

PMID- 8532459
TI  - Children's version of the Alternative Impairment Index: a pilot study.
AB  - The Alternative Impairment Index, a measure composed of scores derived from the
      Halstead-Reitan Neuropsychological Test Battery, was proposed as a new measure of
      neuropsychological impairment in adults. This pilot study investigated the
      feasibility of a Children's Version of the Alternative Impairment Index. Test
      records for 16 normal and brain-damaged children, between the ages of 9 and 14
      years, who had been administered the complete Halstead-Reitan Neuropsychological
      Test Battery for Older Children, were obtained and the Children's Version of the
      Alternative Impairment Index and the Children's Total Neuropsychological Deficit
      Score were compared for agreement on severity. Agreement, i.e., 56% or 9/16
      correct agreement, was weak.

PMID- 8532460
TI  - Brief behavioral treatment for attention-deficit hyperactivity disorder.
AB  - 7 latency-age children received brief behavioral therapy for Attention Deficit
      Hyperactivity Disorder. The intervention included reinforcing appropriate
      behaviors and punishing negative behaviors, skills training, and parental
      education. There were significant decreases in impulsivity at home and school
      after intervention. These results suggest that brief behavioral interventions
      might decrease impulsivity in ADHD children over the short term, but the sample
      was small and heterogeneous, so replication on a larger sample is required.

PMID- 8532461
TI  - Prevalence of head injury among four-year college students: a replication and
      combined results.
AB  - In a replication of an earlier study, college students were surveyed to assess
      the prevalence of diagnosed head injury or prolonged periods of unconsciousness.
      Results were consistent with previous research and indicated a significant number
      of college students reported a head injury or a prolonged period of
      unconsciousness. The major results of the two studies are reported as combined
      data.

PMID- 8532462
TI  - Body-size estimation in anorexia nervosa.
AB  - The aim was to explore the body-image perception of a group of 20 hospitalised
      anorexic patients, aged 18 to 21 years, undergoing a period of treatment. The
      instrument used was the Askevold nonverbal perception test as modified by
      Allamani and colleagues in 1978 to assess perception of the dimensions of
      different parts of the body by exploiting the capacity to project them into
      space. The four parts were the head, the thoracic area, the abdominal area, and
      the pelvic area. Analysis of responses indicated that anorexic patients
      overestimated the abdominal and pelvic areas much more than the 20 members of the
      control group (50% vs 30%). The areas of the head and thorax were perceived
      almost in their real dimensions by the anorexic patients but were underestimated
      by the control group.

PMID- 8532463
TI  - Measurement and appraisal: a comment on Brook and Brook (1995)

PMID- 8532464
TI  - Differential categorization of words by learning disabled, gifted, and
      nonexceptional students.
AB  - This research was done to answer whether learning disabled students attend to
      different word features than nonexceptional and gifted students and whether there
      is a difference by grade. Word sorts of meaningful and nonsense words were used
      to estimate differences between 145 first- and fifth-grade learning disabled,
      nonexceptional, and gifted groups. Analyses indicated that 54 learning disabled
      students were more likely to provide no response or to give simpler responses
      than 61 nonexceptional or 30 gifted peers. Older children (n = 78) attended to
      more and varied word features, were more likely to focus on recognizable meaning,
      and were more able to use syllables as a tool for sorting than were 67 younger
      children. Significant differences were noted between grade and exceptionality
      groups. Implications for practical application and further research are
      discussed.

PMID- 8532465
TI  - Effects of self-efficacy and dispositional optimism on adherence to step aerobic
      exercise classes.
AB  - This study investigated the effects of generalized and domain-specific
      expectancies on participation in 8 weeks of step aerobic-exercise classes. 154
      university students and staff who registered for step aerobic classes completed
      measures of aerobic self-efficacy and dispositional optimism prior to attending
      their first class. Attendance was taken at each session by the instructors. A
      split at the median on attendance classified participants as dropouts or
      adherers. Analysis indicated that adheres scored significantly higher on self
      efficacy that did dropouts. Adherers and dropouts did not differ on dispositional
      optimism.

PMID- 8532466
TI  - Dream recall and visual memory.
AB  - The present study estimated correlations for 50 subjects among frequency of dream
      recall, length of dream report, and visual memory. Whereas the results confirmed
      the previously found relationship between frequency of dream recall and visual
      memory, influence of visual memory on length of dream report was not found.

PMID- 8532467
TI  - Effects of presentation rate of stimuli on response inhibition in ADHD children
      with and without tics.

PMID- 8532468
TI  - Discriminant effectiveness of psychological state measures in predicting
      performance outcome in karate competition.
AB  - Male Shotokan karate players (karateka) (N = 208) completed the Competitive State
      Anxiety Inventory-2 and the Profile of Mood States about 40 minutes before a
      competition. Single-factor multivariate analysis of variance of preperformance
      mood and anxiety scores indicated significant differences between winning and
      losing competitors. Winners scored higher on Vigor, Anger, and Self-confidence,
      and lower on Tension, Depression, Fatigue, Confusion, Cognitive Anxiety, and
      Somatic Anxiety. Discriminant function analysis showed that 91.96% of
      participants could be correctly classified as winners or losers on the basis of
      preperformance mood scores. This figure rose to 93.47% when scores on the anxiety
      subscales were also included in the discriminant function analysis. Anxiety
      scores alone produced 78.89% discrimination. Mood profiles for winning karateka
      were in line with the "mental health" profile of Morgan except for above-average
      scores on Anger. This result supports the view of McGowan and Miller that anger
      may facilitate performance in karate competition. The capacity of measures of
      psychological state to discriminate performance exceeds previous reports,
      suggesting that karate performance may be exceptionally mood-dependent. These
      results suggest that interventions which increase scores on Vigor and Anger and
      reduce scores on Tension, Depression, Fatigue, and Confusion may be particularly
      efficacious for Shotokan karate performance.

PMID- 8532469
TI  - Effects of Intervention upon precompetition state anxiety in elite junior tennis
      players: the relevance of the matching hypothesis.
AB  - The matching hypothesis proposes that interventions for anxiety should be matched
      to the modality in which anxiety is experienced. This study investigated the
      relevance of the matching hypothesis for anxiety interventions in tennis. Elite
      junior tennis players (N = 100; Age: M = 13.9 yr., SD = 1.8 yr.) completed the
      Competitive State Anxiety Inventory-2 before and after one of four randomly
      assigned intervention strategies approximately one hour prior to competition at a
      National Junior Championship. A two-factor multivariate analysis of variance
      (group x time) with repeated measures on the time factor gave no significant main
      effect by group but indicated significant reductions in somatic anxiety and
      cognitive anxiety and a significant increase in self-confidence following
      intervention. A significant group by time interaction emerged for self
      confidence. The results question the need to match intervention strategy to the
      mode of anxiety experienced.

PMID- 8532470
TI  - Observation of response strategies in cycling time trials.
AB  - Athletes in sprint events use various mental and physical starting strategies
      prior to beginning a race. Included among these strategies are sensory-set and
      motor-set strategies. A sensory-set strategy is one in which the athlete
      concentrates on reacting as fast as possible to an auditory or visual stimulus. A
      motor-set strategy is one in which the athlete consciously attends to a component
      of a well-learned skill rather than to the stimulus which evokes the initiation
      of the skill. The purpose of this study was to observe differences in starting
      techniques of 20 championship cyclist responded significantly faster after the
      auditory stimulus and recorded faster 1/2-lap split times than 10 proficient
      cyclists. Strategy selection and use of elite cyclists should be investigated
      further to examine efficient starting strategies and procedures.

PMID- 8532471
TI  - Effects of abdominal and thoracic breathing upon multiple-site electromyography
      and peripheral skin temperature.
AB  - Peripheral finger temperature, frontalis and upper trapezius EMG, and self-report
      of arousal were assessed for four subjects during abdominal and thoracic
      breathing in a single-subject reversal design. Two subjects displayed significant
      differences between abdominal and thoracic breathing conditions; one for
      frontalis EMG, trapezius EMG, and self-report of arousal and one for trapezius
      EMG. Two subjects showed no significant effects. All subjects reached performance
      criteria during training sessions. Abdominal breathing performance during
      reversals was 100% and 92% of sampled breath cycles for the two subjects who
      showed significant change, and 65% and 42% for the two subjects who showed none.
      Methodological issues for measurement of breathing patterns and peripheral skin
      temperature are discussed.

PMID- 8532472
TI  - Relationships among language domains in preterm children.
AB  - Measures of performance in phonology, syntax, semantics, and pragmatics were
      obtained from the language samples of 29 preterm children at preschool age. A
      correlation of .43 was found between measures of phonology and syntax but other
      significant relationships were not found. Results are discussed relative to other
      research.

PMID- 8532473
TI  - Characteristics of elementary school principals and their support for the
      physical education program.
AB  - The purpose was to describe the characteristics of elementary school principals
      who support elementary physical education programs. A statewide random sample of
      500 elementary school principals and their respective elementary physical
      education teachers (n = 500) were mailed questionnaires. A total of 321
      principals responded (64%) to a 20-item questionnaire which assessed their
      physical fitness and their perceptions of elementary physical education. A total
      of 340 physical education teacher (68%) responded to a 23-item survey assessing
      their perceptions of their elementary principals' support for the physical
      education program. The majority of teachers perceived their principals to be
      supportive of them and the physical education program. A series of t tests showed
      no significant differences in principals' age, gender, years of experience as a
      principal, or how important they thought health and physical education was
      compared to other subjects taught in the elementary school and how supportive of
      physical education the principals were perceived to be. Finally, a stepwise
      backward multiple regression analysis indicated that seven variables, including
      fitness of the principal and body mass index, did not explain more than 13% of
      the variance in teachers' perceived support by principals.

PMID- 8532474
TI  - An untenable rationale for treating insomnia.
AB  - In 1995 Cholitz tested a breathing technique to treat insomniacs. The results
      were incomparably much better than typically reported. It is argued that Cholitz'
      explanation of his findings is untenable and that independent replications are
      needed.

PMID- 8532475
TI  - Visual inspection alone produces a decrement in the horizontal-vertical illusion.
AB  - Subjects inspected either inverted-T or L figures for 5 min. and then shortened
      the extended vertical lines of inverted-T figures in an attempt to make the
      vertical line equal in length to the horizontal line. Those who inspected
      inverted-T figures were more accurate on initial trials than controls (who did
      not inspect figures), those who inspected L figures, or those who inspected
      inverted-T figures and made adjustments on the inspected figures. The results
      indicate that visual inspection alone can produce a decrease in the Horizontal
      Vertical illusion and may account, in part, for changes in strategic factors
      which have been hypothesized to underlie illusion decrement.

PMID- 8532476
TI  - Symptoms during load carrying: effects of mass and load distribution during a 20
      km road march.
AB  - Soldiers must often carry heavy loads which can lead to symptoms of body
      soreness, aches, pains, and tiredness. This study assessed symptoms when soldiers
      carried loads in the standard U.S. Army ALICE pack (a single backpack) and in a
      prototype Double Pack (a two-pack system designed to alleviate symptoms by evenly
      distributing the load between a backpack and a frontpack). Each of 15 male
      soldiers completed a 20-km (12.4 mi) road march while carrying either 34, 48, or
      61 kg (75, 105, or 135 lb) and while wearing either the ALICE pack or the Double
      Pack. Symptoms included feeling alert, good, and wide awake. Postmarch symptoms
      included tiredness, muscle tightness, and soreness of the legs, feet, back, and
      shoulders. Analyses of eight symptom factors showed that (a) as load increased,
      fatigue and muscle discomfort intensified, and alertness and feelings of well
      being diminished and (b) distress and heat-illness indices were most intense at
      61 kg with the Double Pack.

PMID- 8532477
TI  - Alexithymia, affect recognition, and five factors of personality in substance
      abusers.
AB  - A total of 80 adults (40 normal volunteers, 40 substance abusers) participated in
      a study about alexithymia and five factors of personality, measured on the
      Toronto Alexithymia Scale and the NEO Five Factor Inventory, respectively, and
      their relationship to recognition of affect. The substance abusers scored the
      same as the age- and sex-matched normal volunteers on recognizing posed facial
      expressions, but higher on the alexithymia scale, while on Neuroticism and
      Extraversion they had lower scores on Agreeableness.

PMID- 8532478
TI  - Comment on: measurement and appraisal (Dewe, 1995)
AB  - Response to two issues raised by Dewe is provided. The tree diagram permits a
      different view of data and may be utilized with various models.

PMID- 8532479
TI  - Relationships between measures of phonological performance in preterm children.
AB  - Percent Consonants Correct (PCC) was computed for spontaneous connected speech
      samples and responses on a single-word articulation test from 29 preterm children
      in preschool. Maturity of speech motor control was also assessed. Moderate
      intercorrelations of all measures are mentioned with regard to clinical
      implications.

PMID- 8532480
TI  - A study of physiological response during emotional imaging.
AB  - We inspected Lang's bio-informational theory and furthered the research. 24
      subjects were divided into two groups, a stimulus group (S-group) and a response
      group (R-group) for scripts with Joy, Anger, and Neutral emotions. In the
      training session, the S-group was instructed to image the scripts as vividly as
      possible, while the R-group was instructed to concentrate on physiological and
      physical responses in addition to what was asked of the S-group. On the test day,
      subjects imaged two Neutral scripts, two standard emotional scripts, and two
      personally relevant emotional scripts. Indices were physiological response (blood
      pressure) and subjects' ratings for imaging. We confirmed that emotional scripts
      increased physiological responses more than nonemotional scripts did. The results
      suggested that the differences in the scripts' content affected blood pressure
      and subjects' ratings of imaging.

PMID- 8532481
TI  - Is the gender of a suicide note writer associated with judgments made about the
      suicide?

PMID- 8532482
TI  - Effects of induced social roles on the High School Personality Questionnaire.
AB  - A one-way multivariate analysis of variance design with a control group (regular
      directions) and three treatment groups using induced social roles (Faking Good,
      Teacher, and Ideal Teacher) as independent variables and the High School
      Personality Questionnaire primary scores as dependent variables was used.
      Subjects were 384 male high school students from Grades 9 through 12. Within each
      classroom, students were randomly assigned to the four groups noted above. A
      broad pattern of differences in scores on primary and secondary personality
      dimensions were obtained. Significant differences between the control (standard
      directions) and the Faking Good, Teacher, and Ideal Teacher roles were obtained
      on three secondary and most of the primary personality dimensions. In several
      cases the ideal social role and neutral social role showed distinct differences
      from the more pervasive favorable impression role.

PMID- 8532483
TI  - Harmonic relationship between preferred tempi and heart rate.
AB  - Since people tend to prefer musical tempi ranging from 70 to 100 beats per
      minute, cyclic physiological response like heart rate is considered on of the
      factors affected by tempo preference. The present study aimed to examine the
      relationship between preferred tempi and heart rate. Subjects were instructed to
      find their favorite tempi while their hart rates were being measured. The
      presented tone stimulus was 440 Hz, 60 dB pressure of pure tone, and the
      presented tempo varied from 10 to 300 cycles per minute. The relationship between
      heart rate and preferred tempo was examined to calculate the density function of
      ratios of preferred tempi to heart rate. This density function indicated that
      preferred tempi were distributed mostly one, one and a half, and two times as
      fast as heart rate. This finding indicated preferred tempi had a simple harmonic
      relationship to heart rate.

PMID- 8532484
TI  - Zero effect of crowding on arousal and performance: on 'proving' the null
      hypothesis.
AB  - This study examined the effect of crowded versus uncrowded conditions upon pulse
      and self-rated arousal, and upon verbal production performance in subjects' first
      and second languages. Participants were 52 francophone college students. Arousal
      estimates were identical for crowded and noncrowded conditions as was verbal
      performance, thereby contradicting the theories of Zajonc (1965) and Freedman and
      Perlick (1979) in which crowding is viewed as an activating and intensifying
      stimulus. Crowding itself appears to have no direct effect on arousal or
      behaviour as measured.

PMID- 8532485
TI  - Digit and shape memory function in soroban learners: are soroban learners
      superior in general?
AB  - The memory function of 15 soroban learners and 13 novices was examined on visual
      memory tasks. Analysis showed soroban learners were superior in performance of
      digit recall but not of shape recall. This result seems to reflect the tendency
      for soroban groups to be better in processing some kinds of spatial than
      categorical properties. Based upon these results, effects of soroban learning on
      brain function were discussed.

PMID- 8532486
TI  - Adolescent perceptions of body weight and weight satisfaction.

PMID- 8532487
TI  - Geophysical variables and behavior: LXXIX. Overt limbic seizures are associated
      with concurrent and premidscotophase geomagnetic activity: synchronization by
      prenocturnal feeding.
AB  - Approximately 35% of the variance (multiple r = 0.59) in the proportion of overt
      seizures (forelimb clonus) within a group of 35 chronically epileptic male rats
      during 65, daily 10-min. observation periods was significantly accommodated by
      the variations in the magnitude of the increased geomagnetic activity at the same
      time as the seizures and with activity during the previous midscotophase. The
      results supported the hypothesis that increased geomagnetic activity during
      specific subintervals of the circadian period suppresses the activity of the
      endogenous anticonvulsant melatonin and lowers the threshold for paroxysmal
      electrical seizures. The possibility of employing large populations of (limbic)
      epileptic patients as a network or a very large array of biomonitors for
      geomagnetic activity is considered.

PMID- 8532488
TI  - Is it rational to have reasons for not committing suicide?

PMID- 8532489
TI  - Temporal delays in incorporation of events into dreams.
AB  - 20 subjects viewed an emotionally arousing video and then recorded their dreams
      at home for seven nights. Dreams were subsequently rated for the likelihood that
      some aspect of the video had been incorporated. For subjects who showed strong
      evidence of incorporation, mean likelihood of incorporation ratings followed a U
      shaped pattern, with significantly higher scores on Nights 1, 6, and 7 than on
      Night 4. The similarity of this temporal pattern with REM sleep patterns observed
      in rats exposed to various learning experiences is noted, and the role of the
      hippocampus as a possible neural mechanism for delayed incorporations is
      discussed.

PMID- 8532490
TI  - Odor discrimination and recognition memory as a function of familiarization.
AB  - The role of olfactory familiarization in short-term recognition of odors was
      investigated. Subjects were asked to make qualitative similarity judgments
      regarding either identical or dissimilar odors delivered in pairs. Except for
      control groups, subjects got familiarized with either the first (target) or the
      second (distractor) or both odors from a pair. Groups also differed according to
      the number of familiarization sessions--one, two, or three--taking place prior to
      the discrimination judgments. There was no significant influence of
      familiarization on correct recognition scores for pairs of identical odors. The
      most salient finding was a marked decrease of false alarms as a function of the
      number of familiarization sessions, which evidenced a positive effect of
      familiarization on discrimination for pairs of dissimilar odors. These judgments
      were not dependent on an intensity criterion. False alarms did not vary according
      to whether subjects had been familiarized with the target or the distractor or
      both odors from a pair. A positive correlation found between discrimination
      performances and the number of odors correctly remembered as being presented
      during familiarization suggested that familiarization resulted in long-term
      storing of memory traces for familiarized odors. Since familiarization was
      effective despite conditions unfavorable to the use of semantic encoding, the
      results argue in favor of a predominantly perceptual encoding of odors in the
      investigated task.

PMID- 8532491
TI  - Brightness constancy in a Ganzfeld environment.
AB  - In this paper, experiments are described in which brightness constancy was
      studied in a Ganzfeld environment. Luminance variation by means of neutral
      density filters was applied to stimuli consisting of a Ganzfeld with superimposed
      disks. To this end, a special-purpose apparatus was constructed. Sequential
      dichoptical brightness matches with a reference stimulus were carried out for the
      disks as well as the homogeneous surround. The results of these measurements
      indicate that (1) besides a clear tendency toward brightness constancy, small but
      systematic effects of the average luminance level are present and (2) the
      brightness of the Ganzfeld is hardly affected by the presence of the disks.
      Finally, it is shown that the experimental results can be modeled adequately in
      terms of a concept that involves an accumulation of contrast information.

PMID- 8532492
TI  - Brightness indention: a novel compression mechanism in the luminance-brightness
      mapping.
AB  - In a previous study, Schouten and Blommaert (1995) explicitly showed that
      brightness constancy implies a substantial compression in the luminance
      brightness mapping. Here it is argued that additional compression mechanisms are
      required for scenes with large luminance ranges. To trace these, a series of
      experiments was conducted which involved expansion of the luminance range. We
      used a simple spatial configuration consisting of a disk on a contourless
      homogeneous surround (Ganzfeld). The contrast between the disk and Ganzfeld acted
      as the independent variable, while the size of the disk was parametrically
      varied. Sequential dichoptical brightness matches with a reference were carried
      out for both the disk and the surround. The results reveal a compression
      mechanism which we term brightness indention. This indention, which has not
      previously been reported in the literature, only occurs if the Ganzfeld is less
      luminous than the disk, and it takes the form of a brightness decrease of the
      immediate surroundings of the disk.

PMID- 8532493
TI  - Segregation by color and stereoscopic depth in three-dimensional visual space.
AB  - Two experiments were conducted to investigate how color and stereoscopic depth
      information are used to segregate objects for visual search in three-dimensional
      (3-D) visual space. Eight observers were asked to indicate the alphanumeric
      category (letter or digit) of the target which had its unique color and unique
      depth plane. In Experiment 1, distractors sharing a common depth plane or a
      common color appeared in spatial contiguity in the xy plane. The results suggest
      that visual search for the target involves examination of kernels formed by
      homogeneous items sharing the same color and depth. In Experiment 2, the xy
      contiguity of distractors sharing a common color or a common depth plane was
      varied. The results showed that when target-distractor distinction becomes more
      difficult on one dimension, the other dimension becomes more important in
      performing visual search, as indicated by a larger effect on search time. This
      suggests that observers can make optimal use of the information available.
      Finally, color had a larger effect on search time than did stereoscopic depth.
      Overall, the results support models of visual processing which maintain that
      perceptual segregation and selective attention are determined by similarity among
      objects in 3-D visual space on both spatial and nonspatial stimulus dimensions.

PMID- 8532494
TI  - Relationship between flanker identifiability and compatibility effect.
AB  - What is the relation between the identifiability of masked flankers and their
      ability to induce compatibility effects in a letter classification task? Using a
      within-subjects design (n = 8), we first determined identification performance
      for two flankers (H or N) around an irrelevant target letter as a function of the
      time (stimulus onset asynchrony, or SOA) after which the flankers were masked. In
      a second condition, subjects classified the central letter of the same stimulus
      patterns irrespectively of the identity of the flankers. The compatibility
      effects increased with increasing identification performance as a function of
      SOA, and we found a significant compatibility effect even at an SOA at which the
      identifiability of the flankers did not differ significantly from zero. We
      discuss the statistical power of our design and an interpretation of our results
      in terms of a dissociation between perceptual processes and processes directly
      activating the motor system (direct parameter specification; cf. Neumann, 1990).

PMID- 8532495
TI  - Repetition blindness under minimum memory load: effects of spatial and temporal
      proximity and the encoding effectiveness of the first item.
AB  - Repetition blindness (RB) refers to the reduced performance in reporting a
      repeated as opposed to a nonrepeated item in rapid serial visual presentation. In
      Experiment 1, we found RB for two-item stimuli in uncertain locations. The
      magnitude of RB decreased significantly with increases in interstimulus interval,
      but not with increases in spatial separation, indicating that RB is determined
      primarily by temporal factors. In Experiment 2, we found RB when subjects were
      required to report only the second of two successively presented items. The
      magnitude of RB increased with the duration of the first item, indicating that RB
      is determined by the encoding effectiveness of the first item. The results of
      this study collectively indicate that RB is not a memory or a sensory phenomenon,
      but rather a perceptual phenomenon occurring at the stage of identity encoding.
      The findings also undermine the arguments (Kanwisher, 1987) that have been
      offered in favor of the type-token binding failure hypothesis and indicate
      instead that type-node refractoriness may be the cause of RB.

PMID- 8532496
TI  - Pure feedback effects in absolute identification.
AB  - To reveal the pure effects of trial-by-trial feedback on judgmental accuracy and
      sequential dependencies independent of global anchoring effects and other
      influences, we presented subjects with sequences consisting alternately (within
      an experimental session) of short runs of trials with feedback (feedback
      sequences) and without feedback (no-feedback sequences). In Experiments 1 and 2
      (absolute identification of sound intensity and sound frequency, respectively),
      judgmental accuracy was the same in the feedback and the no-feedback sequences,
      contrary to previous results. Also, in the feedback sequences, the dependency of
      the current response on the immediately preceding stimulus was larger than that
      in the no-feedback sequences, while the dependency on the previous response was
      larger in the no-feedback sequences. In Experiment 3 (absolute identification of
      sound frequency), we attempted to separate the effects of the number of response
      categories on sequential dependencies from the effects of the number of stimuli.
      The results showed that the number of response categories had a larger effect
      than the number of stimuli on most aspects of performance, but that both affected
      sequential dependencies. These results are generally consistent with a theory of
      absolute identification in which feedback affects judgmental accuracy by
      improving long-term memory for judgmental anchors, while feedback affects
      sequential dependencies by altering response biases.

PMID- 8532497
TI  - Effects of event structure on retrospective duration judgments.
AB  - Two experiments examined whether varying degrees of event coherence influence the
      remembering of an event's actual duration. Relying on musical compositions
      (Experiment 1) or filmed narratives (Experiment 2) as experimental stimuli, the
      underlying hierarchy of information within events (i.e., melodic intervals or
      story elements) was either attentionally highlighted or obscured by placing a
      varying number of accents (i.e., prolonged notes or commercial breaks) at
      locations that either coincided or conflicted with grammatical phrase boundaries.
      When subjects were unexpectedly asked to judge the actual duration of events,
      through a reproduction (Experiment 1) or verbal estimation (Experiment 2) task,
      duration estimates became more accurate and less variable when the pattern of
      accentuation increasingly outlined the events' nested relationships. Conversely,
      when the events' organization was increasingly obscured through accentuation,
      time judgments not only became less accurate and more variable, but were
      consistently overestimated. These findings support a theoretical framework
      emphasizing the effects of event structure on attending and remembering
      activities.

PMID- 8532498
TI  - A corpus of 714 full-color images of depth-rotated objects.
AB  - A set of full-color images of objects is described for use in experiments
      investigating the effects of in-depth rotation on the identification of three
      dimensional objects. The corpus contains up to 11 perspective views of 70
      nameable objects. We also provide ratings of the "goodness" of each view, based
      on Thurstonian scaling of subjects' preferences in a paired-comparison
      experiment. An exploratory cluster analysis on the scaling solutions indicates
      that the amount of information available in a given view generally is the major
      determinant of the goodness of the view. For instance, objects with an elongated
      front-back axis tend to cluster together, and the front and back views of these
      objects, which do not reveal the object's major surfaces and features, are
      evaluated as the worst views.

PMID- 8532499
TI  - Perception of relative pitch with different references: some absolute-pitch
      listeners can't tell musical interval names.
AB  - Two experiments were conducted to examine the effect of absolute-pitch possession
      on relative-pitch processing. Listeners attempted to identify melodic intervals
      ranging from a semitone to an octave with different reference tones. Listeners
      with absolute pitch showed declined performance when the reference was out-of
      tune C, out-of-tune E, or F#, relative to when the reference was C. In contrast,
      listeners who had no absolute pitch maintained relatively high performance in all
      reference conditions. These results suggest that absolute-pitch listeners are
      weak in relative-pitch processing and show a tendency to rely on absolute pitch
      in relative-pitch tasks.

PMID- 8532500
TI  - Perception of partly occluded objects by young chicks.
AB  - Completion of partly occluded objects is a ubiquitous phenomenon in human visual
      perception. It is unclear, however, whether it occurs at all in other species:
      Studies on visual discrimination learning have revealed that animals usually
      attend to parts and features of the discriminative stimuli rather than to global
      object properties. We provide here the first demonstration of recognition of
      partly occluded objects in a bird species, the domestic chick Gallus gallus,
      using the naturalistic setting made available by filial imprinting, a process
      whereby young birds form attachments to their mothers or some artificial
      substitute. In Experiment 1, newborn chicks were reared singly with a red
      cardboard triangle, to which they rapidly imprinted and therefore treated as a
      social partner. On Day 3 of life, the chicks were presented with pairs of objects
      composed of either isolated fragments or occluded parts of the imprinting
      stimulus. Chicks consistently chose to associate with complete or with partly
      occluded versions of the imprinting object rather than with separate fragments of
      it. Similarly, in Experiment 2, chicks reared with a partly occluded triangle
      chose to associate with a complete triangle rather than with fragmented one,
      whereas chicks reared with a fragmented triangle chose to associate with a
      fragmented triangle and not with a complete one. Newborn chicks thus appear to
      behave as if they could experience amodal completion.

PMID- 8532501
TI  - Evaluation of a dynamical model of speech perception.
AB  - Previous work (Tuller, Case, Ding, & Kelso, 1994) has revealed signature
      properties of nonlinear dynamical systems in how people categorize speech sounds.
      The data were modeled by using a two-well potential function that deformed with
      stimulus properties and was sensitive to context. Here we evaluate one prediction
      of the model--namely, that the rate of change of the potential's slope should
      increase when the category is repeatedly perceived. Judged goodness of category
      membership was used as an index of the slope of the potential. Stimuli from a
      "say"-"stay" continuum were presented with gap duration changing sequentially
      throughout the range from 0 to 76 to 0 msec, or from 76 to 0 to 76 msec. Subjects
      identified each token as either "say" or "stay" and rated how good an exemplar it
      was of the identified category. As predicted, the same physical stimulus
      presented at the end of a sequence was judged a better exemplar of the category
      than was the identical stimulus presented at the beginning of the sequence. In
      contrast, stimuli presented twice near the middle of a sequence with few (or no)
      stimuli between them, as well as stimuli presented with an intervening random
      set, showed no such differences. These results confirm the hypothesis of a
      context-sensitive dynamical representation underlying speech.

PMID- 8532502
TI  - Effects of stimulus variability on perception and representation of spoken words
      in memory.
AB  - A series of experiments was conducted to investigate the effects of stimulus
      variability on the memory representations for spoken words. A serial recall task
      was used to study the effects of changes in speaking rate, talker variability,
      and overall amplitude on the initial encoding, rehearsal, and recall of lists of
      spoken words. Interstimulus interval (ISI) was manipulated to determine the time
      course and nature of processing. The results indicated that at short ISIs,
      variations in both talker and speaking rate imposed a processing cost that was
      reflected in poorer serial recall for the primary portion of word lists. At
      longer ISIs, however, variation in talker characteristics resulted in improved
      recall in initial list positions, whereas variation in speaking rate had no
      effect on recall performance. Amplitude variability had no effect on serial
      recall across all ISIs. Taken together, these results suggest that encoding of
      stimulus dimensions such as talker characteristics, speaking rate, and overall
      amplitude may be the result of distinct perceptual operations. The effects of
      these sources of stimulus variability in speech are discussed with regard to
      perceptual saliency, processing demands, and memory representation for spoken
      words.

PMID- 8532503
TI  - [Dissection-like artifact on one-second scanning time CT].
AB  - Dissection-like artifact (DLA) is noted only on one-second scanning time CT
      image. It is usually observed in the ascending aorta, and less commonly in the
      superior vena cava and right pulmonary artery. We evaluated 136 cases of thoracic
      CT (including 20 cases of heart failure), and examined how often and where the
      artifact is noted and why it is produced. DLA was noted in the ascending aorta in
      99 cases. Among the 99 cases, the same artifacts were also shown in the superior
      vena cava in 26 cases, and in the right pulmonary artery in 10 cases. DLA was
      never observed in other great vessels, such as the descending aorta and inferior
      vena cava. This artifact was not demonstrated in patients with heart failure. We
      presume that DLA is produced by pulsation of the ascending aorta and pulmonary
      artery. If the artifact is observed, the patient does not have severe cardiac
      impairment.

PMID- 8532504
TI  - [Experimental and clinical trial of degradable starch microspheres (DSM) in
      treatment of hepatic neoplasm: Part 2. Clinical study].
AB  - Hepatic chemotherapy with DSM was performed in 63 patients (45 patients with
      hepatocellular carcinoma and 18 patients with liver metastases). Two patients
      showed complete response and 12 patients showed partial response. The greater the
      blockade of arterial blood flow, the better the clinical response seemed.
      Analysis of changes in CT images after hepatic chemotherapy with DSM revealed
      that, in addition to enhancement of the effect of the anticancer drugs by
      blockade of blood flow, DSM also had an ischemic effect. In conclusion, DSM used
      together with anticancer drug may improve the therapeutic effects.

PMID- 8532505
TI  - [Histopathological analysis of A-P shunt in peripheral intrahepatic
      cholangiocarcinoma].
AB  - A-P shunts observed in peripheral intrahepatic cholangiocarcinoma were analyzed
      histopathologically. The study group consisted of 30 patients who underwent
      angiography at Saitama Medical School between February 1980 and July 1992.
      Histopathological analysis was done from biopsy, surgery and/or autopsy specimen.
      The male to female ratio was 7 to 8, and the mean age of the subjects was 61.3
      years. All cases were adenocarcinoma and the histological grade was poorly
      differentiated in 43.3%, moderate in 23.3% and well differentiated in 33.3%. A-P
      shunt was observed clearly in 2 patients (6.7%), one was poorly differentiated
      and the other was moderate. Histological study showed dominant tumor invasion
      into hepatic lobules, and hepatic arterial and portal vein branches, excessive
      fibrous tissue within and around the tumor and Glisson's sheath. Is there more?

PMID- 8532506
TI  - [Uterine cervical cancer: usefulness of MR imaging after the initial radiation
      therapy].
AB  - To evaluate the usefulness of magnetic resonance imaging (MRI) in diagnosing
      residual or recurrent tumors of cervical cancer after radiation therapy, we
      investigated the time difference between MRI and gynecologic findings in the
      diagnosis of residual or recurrent tumor in 12 patients with invasive cervical
      cancer. We defined a positive finding for residual or recurrent tumor as an
      uterine cervical mass isointense to muscle on T1-weighted images and hyperintense
      on T2-weighted images, and when a positive biopsy specimen was obtained. Two
      patients were diagnosed as having a residual or recurrent tumor by MRI.
      Positivity was demonstrated four and seven months later, respectively. MRI was
      more useful in the earlier diagnosis of residual or recurrent tumor of cervical
      cancer after radiation therapy than uterine biopsy. There was one patient whose
      differentiation from residual tumor or radiation-induced necrosis or inflammation
      on MRI was difficult. MRI and gynecologic check-up at a regular interval after
      radiation therapy was needed to distinguish them. One patient was diagnosed as
      having a recurrent tumor by gynecologic finding three month earlier than by MRI.
      Follow-up MRI examinations at a regular interval in addition to gynecologic
      examination is necessary for the early detection of recurrent cervical cancer
      after radiation therapy.

PMID- 8532507
TI  - [Whole abdominal irradiation for peritoneal dissemination of alimentary tract
      cancers].
AB  - Between January 1986 and August 1991, 19 patients with alimentary tract cancers
      complicated by peritoneal dissemination received whole abdominal irradiation
      combined with intraperitoneal chemotherapy postoperatively. Using a moving-strip
      technique of irradiation, 12.0 Gy was delivered in three fractions to the entire
      abdominal contents with partial liver and kidney shielding. The primary tumor
      sites were the stomach in 12 patients, the colorectum in five, and the gall
      bladder in two. Nine patients with gross residual disease also received a limited
      field boost of 30.6 Gy in 17 fractions after completion of treatment to the whole
      abdomen. None of the patients failed to complete the planned dose despite acute
      gastrointestinal toxicity (nausea and vomiting, 84%, diarrhea and cramping, 78%)
      and acute hematologic toxicity (leukocytopenia, 84%, thrombocytopenia, 68%). Our
      follow-up study revealed that the actuarial one-year survival rate was 28.4% and
      the median survival time was 9.0 months. Survival rates at one-year for patients
      with colorectal and gastric cancer were 75.0% and 16.7%, respectively. Patients
      with gastric cancer (n = 12) had a poorer outcome than those with colorectal
      cancer (n = 5) in the present study. One reason for this difference may have been
      the presence of cancerous pleuritis, which was frequently observed in patients
      with gastric cancer. Therefore, more intensive treatment to prevent cancerous
      pleuritis seems to be necessary to improve the efficacy of whole abdominal
      irradiation.

PMID- 8532508
TI  - [Unilateral effective renal plasma flow measurement using one-compartment
      analysis of 99mTc-MAG3 and gamma-camera renography].
AB  - The aim of this study was to establish a simple and accurate procedure to
      calculate the unilateral effective renal plasma flow (ERPF) using 99mTc-MAG3
      gamma-camera renographyl. Eleven patients with urological disorders were studied
      with 99mTc-MAG3 to calculate the renal uptake ratio (RUR), which was defined as
      the ratio of absorption-corrected renal counts within 1-2 min after intravenous
      injection to injection radioactivity measured with a gamma-camera. We assumed
      that 99mTc-MAG3 was distributed in the circulation, moved from the circulation to
      the kidneys, and was excreted solely from the kidneys. We thus adopted an one
      compartment model to calculate 99mTc-MAG3 clearance (CLMAG) using RUR. Sequential
      p-aminohippurate (PAH) clearance study was performed as a gold standard in all
      the patients to compare CLMAG and PAH clearance. Obtained CLMAG correlated well
      with PAH clearance, and this one-compartment model seemed appropriate for
      describing CLMAG. Unilateral ERPF was accurately measured within two minutes
      after the intravenous injection of 99mTc-MAG3 in conjunction with the renal
      imaging study. This procedure is simple and reliable, and requires no blood or
      urine sampling.

PMID- 8532509
TI  - [Estimation of effective dose from CT examination].
AB  - Tissue or organ doses related to radiological risk were determined for four
      different types of CT scanners with a spiral scan function. Dose measurements
      were performed using a Rando phantom and two types of thermoluminescent
      dosimeters. The effective doses recommended by the International Commission on
      Radiological Protection in 1990 were evaluated using the tissue or organ doses
      determined with the phantom measurement. The resultant effective dose per CT
      examination ranged from 4.6 to 10.8 mSv for chest examination and from 6.7 to
      13.3 mSv for upper abdominal examination. It should be noted that the effective
      dose from CT examination will be increased by increasing in the frequency of CT
      examinations and technical development of CT scanners.

PMID- 8532510
TI  - [Measurement of radical in irradiated experimental tumor: direct detection of
      ascorbate radical in mice using ESR].
AB  - We measured ascorbate radical (AR) produced by the reaction of ascorbic acid
      (Asc) with hydroxyl radical (.OH) or superoxide (O2-) after irradiation in normal
      muscle and SCC-VII tumor of C3H/He mice. AR can be measured using electron spin
      resonance (ESR) equipment and the dialysis method. The tube for collecting AR was
      inserted such that the dialysis membrane was in contact with the normal thigh or
      the center of the tumor lesion. The AR in the interstitial fluid around the
      membrane was collected through the dialysis membrane. After irradiation with 10
      Gy, AR increased in both the normal muscle and tumor tissue; the percent increase
      was 53.1% for normal muscle tissue and 33.8% for tumor tissue. The maximum
      percent increases in AR in the normal muscle and the tumor tissue were 11.7 and
      9.5% for 2.5 Gy, 28.5 and 18.5% for 5 Gy, 53.1 and 33.8% for 10 Gy, and 88.5 and
      44.8% for 15 Gy, respectively. The amount of AR increased to maximums of 144.3%
      and 160.1% after treatment with H2O2 and FeCl2, respectively, while it decreased
      to minimums of 65.3% and 81.3% after treatment with superoxide dismutase (SOD)
      and catalase, respectively. These results suggest that the amount of .OH and O2-
      is reflected in the amount of AR production. This method is useful for the
      following reasons. First, no special treatment, such as freezing of the samples,
      and no administration of noxious agents are necessary. Second, irradiation using
      a dose of only several Gy shows an increase in the production of AR. Third, this
      method is less invasive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532511
TI  - [MR venography using 3D-fast STIR sequence for lower extremities].
AB  - Venography of the lower extremities performed by injecting iodinated contrast
      material requires a complicated technique. Veins of lower-flow-speed such as
      varices are scarcely outlined by using the time-of-flight MR angiography
      technique. On the other hand, the 2D fast SE technique has proven itself
      unsuccessful when used with medium magnetic field MRI equipment in which a very
      long TR is unavailable. We obtained images of lower extremity veins by using the
      3D fast STIR technique and medium magnetic field MRI equipment of 0.5 Tesla. The
      results were crisp angiographic images of lower-flow-speed veins including
      varices.

PMID- 8532512
TI  - [Cystic duct anatomy on DIC-helical CT].
AB  - Laparoscopic cholecystectomy (LC) is becoming increasingly common. When
      performing LC, the surgeon may face the risk of ductal injury because of the
      narrow visual field. Thus, detailed anatomical information on the biliary tree is
      necessary. DIC-helical CT was carried out in 39 patients suspected of having
      biliary diseases. The cystic duct was visualized in all cases. Posterior (30.8%)
      and posterolateral (17.9%) cysticohepatic junction were more common than in
      previous reports. The cystic duct took the anterior course of the bile duct in a
      few cases (12.8%). DIC-helical CT is useful for the noninvasive detection of
      biliary anatomy.

PMID- 8532513
TI  - [Immunohistochemical study of radiation-induced apoptosis and oncogenes].
AB  - Relationships between radiation-induced apoptosis and oncogenes or suppressor
      genes (p53, MDM2, c-myc, p21ras and bcl-2) were immunohistochemically studied in
      7 human tumors transplanted to nude mice. The most radiosensitive
      ependymoblastoma was negative for p53 and c-myc, however, the other 6 tumors were
      positive for them. Following irradiation, the ependymoblastoma became p53
      positive, and showed the highest incidence of apoptosis among the 7 tumors. In
      addition, bcl-2 expression in this tumor was slightly different from that in the
      others.

PMID- 8532514
TI  - Evidence for the late origin of introns in chloroplast genes from an evolutionary
      analysis of the genus Euglena.
AB  - The origin of present day introns is a subject of spirited debate. Any intron
      evolution theory must account for not only nuclear spliceosomal introns but also
      their antecedents. The evolution of group II introns is fundamental to this
      debate, since group II introns are the proposed progenitors of nuclear
      spliceosomal introns and are found in ancient genes from modern organisms. We
      have studied the evolution of chloroplast introns and twintrons (introns within
      introns) in the genus Euglena. Our hypothesis is that Euglena chloroplast introns
      arose late in the evolution of this lineage and that twintrons were formed by the
      insertion of one or more introns into existing introns. In the present study we
      find that 22 out of 26 introns surveyed in six different photosynthesis-related
      genes from the plastid DNA of Euglena gracilis are not present in one or more
      basally branching Euglena spp. These results are supportive of a late origin for
      Euglena chloroplast group II introns. The psbT gene in Euglena viridis, a basally
      branching Euglena species, contains a single intron in the identical position to
      a psbT twintron from E.gracilis, a derived species. The E.viridis intron, when
      compared with 99 other Euglena group II introns, is most similar to the external
      intron of the E.gracilis psbT twintron. Based on these data, the addition of
      introns to the ancestral psbT intron in the common ancester of E.viridis and
      E.gracilis gave rise to the psbT twintron in E.gracilis.

PMID- 8532515
TI  - Cleavage properties of an oligonucleotide containing a bridged internucleotide 5'
      phosphorothioate RNA linkage.
AB  - An oligonucleotide has been synthesized that contains a single bridging 5'
      phosphorothioate at an RNA linkage (5'-ApCpGpGpTpCpTprCpsApCpGpApGpC-3'). This
      new phosphodiester linkage is found to be particularly susceptible to cleavage
      when compared with the corresponding oxo, deoxy and thiodeoxy derivatives.
      Divalent metal cations were observed to dramatically increase the cleavage rate.
      The products of the cleavage under a variety of conditions are a 5'-thiol
      containing fragment (6mer) and a 2',3'-cyclic phosphate-containing fragment
      (8mer). The pseudo-first order rate constant, kobs, for cleavage at pH 7.5 (50 mM
      Tris-HCI) in the presence of 5 mM EDTA is 1.5 x 10(-4)/min. In the presence of 5
      mM metal dichloride and 50 mM Tris-HCI, pH 7.5, the relative cleavage rate
      enhancements are 10, 24, 71, 98, 370 and 3400 for Mg2+, Ca2+, Mn2+, Co2+, Zn2+
      and Cd2+ respectively. The rate enhancements correlate well with Pearson's HSAB
      principle, suggesting that cleavage is mediated in part by coordination of the
      metal to the 5'-mercapto leaving group. RNA linkages containing bridging 5'
      phosphorothioates should prove valuable for studying the mechanistic details of a
      variety of RNA cleaving agents, such as ribozymes.

PMID- 8532516
TI  - Positive and negative roles for cdc10 in cell cycle gene expression.
AB  - In this paper we describe properties of the cdc10-C4 mutant of the fission yeast
      Schizosaccharomyces pombe. The cdc10+ gene encodes a component of the DSC1Sp/MBF
      transcription complex, which is required for cell-cycle regulated expression at
      G1-S of several genes via cis-acting MCB (MIuI cell cycle box) elements. At
      permissive temperatures cdc10-C4 causes expression of MCB-regulated genes through
      the whole cell cycle, which in asynchronously dividing cells is manifested in
      overall higher expression levels. This overexpression phenotype is cold
      sensitive: in cdc10-C4 cells, MCB genes are expressed offprogressively higher
      levels at lower temperatures. In heterozygous cdc10-C4/cdc10+ diploid strains,
      MCB-regulated genes are not overexpressed, suggesting that loss, rather than
      alteration, of function of the cdc10-C4 gene product is the reason for
      unregulated target gene expression. Consistent with this, the cdc10-C4 mutant
      allele is known to encode a truncated protein. We have also overexpressed the
      region of the cdc10 protein absent in cdc10-C4 under the control of an inducible
      promoter. This induces a G1 delay, and additionally causes a reduction of the
      overexpression of MCB genes in cdc10-C4 strains. These results suggest that
      DSC1Sp/MBF represses, as well as activates, MCB gene expression during the cell
      cycle.

PMID- 8532517
TI  - Structural probing and damage selection of citrulline- and arginine-specific RNA
      aptamers identify base positions required for binding.
AB  - In a recent study, an RNA aptamer for the specific recognition of the amino acid
      L-arginine was evolved from an in vitro selected L-citrulline binding parent
      sequence [M. Famulok (1994) J. Am. Chem. Soc. 116, 1698-1706]. We have now
      carried out a structural analysis of these aptamers by using chemical
      modification experiments. Footprinting experiments and a damage selection
      approach were performed to identify those positions protected from modification
      in the presence of the amino acids and modifications that interfere with the
      binding of the ligand. It is shown that of the two bulged regions present in both
      aptamers one can be modified without loss of binding activity whereas in the
      other bulge nearly every position is shown to be involved in the recognition of
      the ligands. This might be indicative for non-canonical base pairing to occur
      within the non-Watson-Crick paired regions which might be stabilized by the
      complexed amino acid. Binding to the cognate amino acid significantly enhances
      the conformational stability of the RNA. We also tested the sensitivity of both
      aptamers towards lead (II) ion induced cleavage and identified a hypersensitive
      cleavage site within the invariant bulged region. Lead cleavage is inhibited by
      the complexed amino acid, indicating a conformational change of the aptamer upon
      ligand binding. NMR titration data obtained with both aptamers and their cognate
      ligands confirm the proposed conformational changes and indicate the formation of
      a 1:1 complex of RNA:amino acid.

PMID- 8532518
TI  - Control of HPV 18 DNA replication by cellular and viral transcription factors.
AB  - Papillomavirus replication in vivo requires the interaction of the virally
      encoded proteins E1 and E2 with the origin of replication which is localised in
      the regulatory region (long control region or LCR) of the viral genome. In
      genital human papillomaviruses (HPVs), the origin overlaps promoter elements of
      early transcription. In this study, we analysed the replication of HPV18 DNA
      using the complete LCR containing mutations in transcription regulatory elements.
      We found that each of the three E2 binding sites proximal to the AT-rich sequence
      of the origin contributes to the replication rate of DNA, although not
      identically. In addition, two sequences important for early transcription, an Sp1
      binding site and the TATA box, were also found to play a role in replication. In
      contrast, two AP1 binding sites required for the enhancer-mediated activation of
      early transcription did not affect the replication, while other upstream
      sequences in the LCR did contribute to the replication efficiency. Our results
      indicate that besides a core origin of replication containing an AT-rich sequence
      and three E2 binding sites, auxiliary elements affect HPV18 DNA replication in
      the context of the full length LCR, some of which are important for
      transcription.

PMID- 8532519
TI  - Methylation of the mouse M-lysozyme downstream enhancer inhibits heterotetrameric
      GABP binding.
AB  - Expression of the mouse M-lysozyme gene is a specific marker for the
      differentiation of macrophage/granulocyte cell lineages. Analysis of the
      mechanisms regulating M-lysozyme gene expression revealed an enhancer element in
      the 3'-flanking region of the gene, termed the M-lysozyme downstream enhancer
      (MLDE). Here we demonstrate that the nuclear factors binding to MLDE are present
      in all tested myeloid and non-myeloid mouse cell lines. Sequence analysis of MLDE
      identified two different sequences, CAGGAAGT and CCGGAAGT, which match the
      consensus binding sequences for proteins of the ets gene superfamily. The two
      sites are oriented palindromicly and separated by 10 bp. DMS/DEPC interference
      assays revealed different patterns of DNA-protein contacts on the two sites.
      Mutation of each consensus sequence leads to an individual change in protein
      binding in vitro. Despite these differences, both sequences are bound by GABP,
      forming a heterotetrameric complex. Tissue specificity is correlated with
      demethylation of a single CpG dinucleotide located in one of the two Ets motifs.
      This site when methylated inhibits GABP binding to both sequences in non
      macrophage cell types.

PMID- 8532520
TI  - Transition state stabilization by the 'high' motif of class I aminoacyl-tRNA
      synthetases: the case of Escherichia coli methionyl-tRNA synthetase.
AB  - Methionyl-tRNA synthetase belongs to the class I aminoacyl-tRNA synthetase family
      characterized both by a catalytic center built around a Rossmann Fold and by the
      presence of the two peptidic marker sequences HIGH and KMSKS. In this study, the
      role of the 21HLGH24 motif of Escherichia coli methionyl-tRNA synthetase was
      studied in a systematic fashion by site-directed mutagenesis. It is shown that
      the two histidine residues play a crucial role in the catalysis of the methionyl
      adenylate formation by participating in the stabilisation of the ATP phosphate
      chain during the transition state. Moreover, the results suggest the involvement
      of the epsilon-imino group of histidine 21 and of the delta-imino group of
      histidine 24. Notably, the substitution of either the leucine or the glycine
      residue of the HLGH motif by alanine had no effect on the catalysis. From the
      data and from other studies with class I aminoacyl-tRNA synthetases, concomitant
      positive contributions of the HIGH and KMSKS sequences to reach the transition
      state of aminoacyl adenylate formation can be envisaged.

PMID- 8532521
TI  - Binding of heat shock factor to and transcriptional activation of heat shock
      genes in Drosophila.
AB  - Heat shock factor (HSF) binds to heat shock elements (HSEs) and the binding can
      be highly cooperative. Here we report an analysis of binding of Drosophila HSF to
      both native and synthetic heat shock regulatory regions. We find that cooperative
      binding of HSF requires close proximity, rather than helical alignment, of HSEs.
      Two or more trimeric HSEs organized as contiguous 5 bp units show much higher
      levels of cooperativity than multiple but separated HSEs. We discuss these in
      vitro observations in the context of the in vivo status of heat shock genes under
      mild and full heat shock conditions. Finally, we show that the DNA binding and
      trimerization domains alone may be sufficient for the full level of binding
      cooperativity between HSF trimers. This last result suggests that close proximity
      of HSEs for cooperative binding of HSF is a result of protein-protein
      interactions near the point of DNA contact.

PMID- 8532522
TI  - Characterization of the human immunoglobulin epsilon mRNAs and their
      polyadenylation sites.
AB  - Several IgE heavy (H) chain transcripts are produced by alternative splicing
      between constant region (CH3 and CH4) and membrane (M1 and M2) exons and by
      differential cleavage-polyadenylation at poly(A) sites downstream of the CH4 and
      M2 exons. We have now characterized the poly(A) signal of the epsilon transcripts
      that contain membrane exon sequences (epsilon CH4-M1'-M2, epsilon CH4-M1-M2,
      epsilon CH4-M2' and epsilon CH4-M2") and have determined the complete sequence of
      the M2 exon and 1.4 kb of downstream genomic DNA. The membrane locus poly(A) site
      was identified by RACE-PCR analysis of epsilon transcripts obtained from IgE
      producing myeloma cells and normal peripheral blood lymphocytes (PBL). All
      membrane exon transcripts were found to be polyadenylated following a CA
      dinucleotide located 1046 nt from the beginning of the M2 exon. An AGTAAA
      hexamer, located 13 nt upstream from the site of cleavage and polyadenylation,
      was the only poly(A) signal sequence present in the 1.4 kb of genomic DNA
      downstream of the M2 exon. A (G+T)-rich region, which is also conserved in most
      poly(A) signals, was present 50 nt downstream of the AGTAAA hexamer. Northern
      blot analysis confirmed that this poly(A) site is used by the membrane exon
      epsilon mRNAs expressed by the U266 myeloma. The four membrane exon transcripts
      were detected in different relative amounts in PBL and IgE-producing myeloma
      cells, which could reflect different epsilon mRNA splicing patterns during B-cell
      differentiation.

PMID- 8532523
TI  - The sequence and context of the 5' splice site govern the nuclear stability of
      polyoma virus late RNAs.
AB  - We have examined the influence of splicing signals on the stability of polyoma
      virus late RNAs in the nucleus. Late primary transcripts contain a single 5'
      splice site and three alternative 3' splice sites. In earlier work we showed that
      the presence of introns was not required for late RNA accumulation, however, the
      5' splice site was essential, as removal of only the 5' splice site was
      sufficient to destabilize late RNAs up to 100-fold when compared with early RNAs.
      A complementary clone which retained the 5' splice site but which carried small
      deletions of all late region 3' splice sites produced wild-type levels of
      unspliced late RNA. In order to extend this work we have constructed additional
      types of mutants. Point mutations in the 5' splice site confirmed its importance
      for RNA stability. Other mutants included constructs in which the spacing between
      the 5' splice site and the late promoter was altered and 5' splice site insertion
      mutants where a 58 bp fragment containing the 5' splice site sequence was
      inserted separately at various restriction sites in the late region. Both types
      of mutants lacked all of the late 3' splice sites and had only a single 5' splice
      site. RNase protection analyses of late and early RNAs from these constructs
      revealed that moving the 5' splice site away from the late promoter (or from its
      normal context) destabilized late RNAs > 10-fold relative to the wild-type. We
      conclude that both 5' splice site integrity and its proximity to the late
      promoter play important roles in the nuclear stability of polyoma virus late
      RNAs.

PMID- 8532524
TI  - Mutations affecting the biosynthesis of S-adenosylmethionine cause reduction of
      DNA methylation in Neurospora crassa.
AB  - A temperature-sensitive methionine auxotroph of Neurospora crassa was found in a
      collection of conditional mutants and shown to be deficient in DNA methylation
      when grown under semipermissive conditions. The defective gene was identified as
      met-3, which encodes cystathionine-gamma-synthase. We explored the possibility
      that the methylation defect results from deficiency of S-adenosylmethionine
      (SAM), the presumptive methyl group donor. Methionine starvation of mutants from
      each of nine complementation groups in the methionine (met) pathway (met-1, met
      2, met-3, met-5, met-6, met-8, met-9, met-10 and for) resulted in decreased DNA
      methylation while amino acid starvation, per se, did not. In most of the strains,
      including wild-type, intracellular SAM peaked during rapid growth (12-18 h after
      inoculation), whereas DNA methylation continued to increase. In met mutants
      starved for methionine, SAM levels were most reduced (3-11-fold) during rapid
      growth while the greatest reduction in DNA methylation levels occurred later.
      Addition of 3 mM methionine to cultures of met or cysteine-requiring (cys)
      mutants resulted in 5-28-fold increases in SAM, compared with wild-type, at a
      time when DNA methylation was reduced approximately 40%, suggesting that the
      decreased methylation during rapid growth in Neurospora is not due to limiting
      SAM. DNA methylation continued to increase in a cys-3 mutant that had stopped
      growing due to methionine starvation, suggesting that methylation is not
      obligatorily coupled to DNA replication in Neurospora.

PMID- 8532525
TI  - NMR studies of DNA duplexes singly cross-linked by different synthetic linkers.
AB  - Molecular modelling studies resulted in the design of a variety of non
      nucleotidic covalent linkers to bridge the 3'-end of the (+)-strand and the 5'
      end of the (-)-strand in DNA duplexes. Three of these linkers were synthesized
      and used to prepare singly cross-linked duplexes d(GTGGAATTC)-linker
      d(GAATTCCAC). Linker I is an assembly of a propylene-, a phosphate- and a second
      propylene-group and is thought to mimic the backbone of two nucleotides. Linkers
      II and III consist of five and six ethyleneglycol units, respectively. The
      melting temperatures of the cross-linked duplexes are 65 degrees C for I and 73
      degrees C for II and III, as compared with 36 degrees C for the corresponding non
      linked nonadeoxynucleotide duplex. The three cross-linked duplexes were
      structurally characterized by nuclear magnetic resonance spectroscopy. The 1H and
      31P resonance assignments in the DNA stem were obtained using standard methods.
      For the resonance assignment of the linker protons, two-dimensional 1H-31P
      heteronuclear COSY and two-quantum-experiments were used. Distance geometry
      calculations with NOE-derived distance constraints were performed and the
      resulting structures were energy-minimized. In duplex I, the nucleotides flanking
      the propylene-phosphate-propylene-linker do not form a Watson-Crick base pair,
      whereas in duplexes II and III the entire DNA stem is in a B-type double helix
      conformation.

PMID- 8532526
TI  - Characterization of the XRCC1-DNA ligase III complex in vitro and its absence
      from mutant hamster cells.
AB  - The human DNA repair protein XRCC1 was overexpressed as a histidine-tagged
      polypeptide (denoted XRCC1-His) in Escherichia coli and purified in milligram
      quantities by affinity chromatography. XRCC1-His complemented the mutant Chinese
      hamster ovary cell line EM9 when constitutively expressed from a plasmid or when
      introduced by electroporation. XRCC1-His directly interacted with human DNA
      ligase III in vitro to form a complex that was resistant to 2 M NaCl. XRCC1-His
      interacted equally well with DNA ligase III from Bloom syndrome, HeLa and MRC5
      cells, indicating that Bloom syndrome DNA ligase III is normal in this respect.
      Detection of DNA ligase III on far Western blots by radiolabelled XRCC1-His
      indicated that the level of the DNA ligase polypeptide was reduced approximately
      4-fold in the mutant EM9 and also in EM-C11, a second member of the XRCC1
      complementation group. Decreased levels of polypeptide thus account for most of
      the approximately 6-fold reduced DNA ligase III activity observed previously in
      EM9. Immunodetection of XRCC1 on Western blots revealed that the level of this
      polypeptide was also decreased in EM9 and EM-C11 (> 10-fold), indicating that the
      XRCC1-DNA ligase III complex is much reduced in the two CHO mutants.

PMID- 8532527
TI  - Intronic U14 snoRNAs of Xenopus laevis are located in two different parent genes
      and can be processed from their introns during early oogenesis.
AB  - U14 is a member of the rapidly growing family of intronic small nucleolar RNAs
      (snoRNAs) that are involved in pre-rRNA processing and ribosome biogenesis. These
      snoRNA species are encoded within introns of eukaryotic protein coding genes and
      are synthesized via an intron processing pathway. Characterization of Xenopus
      laevis U14 snoRNA genes has revealed that in addition to the anticipated location
      of U14 within introns of the amphibian hsc70 gene (introns 4, 5 and 7),
      additional intronic U14 snoRNAs are also found in the ribosomal protein S13 gene
      (introns 3 and 4). U14 is thus far a unique intronic snoRNA in that it is encoded
      within two different parent genes of a single organism. Northern blot analysis
      revealed that U14 snoRNAs accumulate during early oocyte development and are
      rapidly expressed after the mid-blastula transition of developing embryos.
      Microinjection of hsc70 pre-mRNAs into developing oocytes demonstrated that
      oocytes as early as stages II and III are capable of processing U14 snoRNA from
      the pre-mRNA precursor. The ability of immature oocytes to process intronic
      snoRNAs is consistent with the observed accumulation of U14 during oocyte
      maturation and the developmentally regulated synthesis of rRNA during oogenesis.

PMID- 8532528
TI  - A new vector for recombination-based cloning of large DNA fragments from yeast
      artificial chromosomes.
AB  - The functional analysis of genes frequently requires manipulation of large
      genomic regions embedded in yeast artificial chromosomes (YACs). We have designed
      a yeast-bacteria shuttle vector, pClasper, that can be used to clone specific
      regions of interest from YACs by homologous recombination. The important feature
      of pClasper is the presence of the mini-F factor replicon. This leads to a
      significant increase in the size of the plasmid inserts that can be maintained in
      bacteria after cloning by homologous recombination in yeast. The utility of this
      vector lies in its ability to maintain large fragments in bacteria and yeast,
      allowing for mutagenesis in yeast and simplified preparation of plasmid DNA in
      bacteria. Using PCR-generated recombinogenic fragments in pClasper we cloned a 27
      kb region from a YAC containing the Hoxc cluster and a 130 kb region containing
      the entire Hoxb cluster. No rearrangements were seen when the recombinants in the
      shuttle vector were transferred to bacteria. We outline the potential uses of
      pClasper for functional studies of large genomic regions by transgenic and other
      analyses.

PMID- 8532529
TI  - Deregulated messenger RNA expression during T cell apoptosis.
AB  - The IL-2 dependent murine cytotoxic T cell line CTLL-2 undergoes programmed cell
      death when deprived of its specific cytokine. We analyzed the expression of cell
      cycle related genes after IL-2 deprivation. Here we show that a generalized
      decrease and re elevation of the levels of mRNA takes place as part of the
      apoptotic program. The levels of several mRNAs encoding cell cycle functions,
      including cyclin D2, cyclin D3, cyclin B1, c-myc and max all declined at 1.5-3 h
      following IL-2 deprivation. Notably, the maxmRNA, which was shown to be expressed
      in proliferating, growth arrested and differentiated cells, is down regulated
      with the same kinetics as the other mRNAs. Surprisingly, the mRNAs whose levels
      declined at 1.5-3 h rose again at 10-14 h, a time which closely followed the time
      of the first detection of apoptotic DNA degradation, at 8 h, but which precedes
      actual loss of viability, at 14 h, as measured by trypan blue exclusion. Of all
      analyzed genes only the expression of the S-phase specific histone H4 gene
      resists the initial decrease and declines gradually over the course of cell
      death. Measurement of c-Myc protein synthesis at a late stage of the apoptotic
      program revealed that the accumulated reinduced mRNA is not translated into
      protein. Because transcriptional regulation has been shown to be dependent on the
      chromatin structure, the reinduction may be triggered by relaxation of the
      chromatin caused by alterations in the chromatin structure of apoptotic cells.

PMID- 8532530
TI  - Homodimerization of the human U1 snRNP-specific protein C.
AB  - The U1 snRNP-specific protein C contains an N-terminal zinc finger-like CH motif
      which is required for the binding of the U1C protein to the U1 snRNP particle.
      Recently a similar motif was reported to be essential for in vivo
      homodimerization of the yeast splicing factor PRP9. In the present study we
      demonstrate that the human U1C protein is able to form homodimers as well. U1C
      homodimers are found when (i) the human U1C protein is expressed in Escherichia
      coli, (ii) immunoprecipitations with anti-U1C antibodies are performed on in
      vitro translated U1C, and when (iii) the yeast two hybrid system is used.
      Analyses of mutant U1C proteins in an in vitro dimerization assay and the yeast
      two hybrid system revealed that amino acids within the CH motif, i.e. between
      positions 22 and 30, are required for homodimerization.

PMID- 8532531
TI  - A new 2'-hydroxyl protecting group for the automated synthesis of
      oligoribonucleotides.
AB  - We have developed a new type of 2'-hydroxyl protecting group for the automated
      machine synthesis of RNA oligomers: a 2-hydroxyisophthalate formaldehyde acetal
      (HIFA). The unique feature of this protecting group is that, as the bis ester, it
      is relatively stable to the acidic conditions that are used for repeated removal
      of dimethoxytrityl groups during chain elongation, but the final deprotection
      step in alkali, which cleaves the chain from the support and removes the base and
      phosphate protecting groups, converts it to the bis carboxylate and this can be
      removed relatively rapidly by treatment with mild acid. Conversion of the bis
      ester to the bis carboxylic acid increases the rate of acid-catalyzed hydrolysis
      of the acetal by 42-fold at pH 1, and, possibly, by 1320-fold at pH 3. The bis
      ester is 112 times more stable than the 1-(2-fluorophenyl)-4-methoxypiperidin-4
      yl group (Fpmp) towards hydrolysis at pH 1, while the bis acid is only 2.35 times
      more stable than Fpmp at pH 3. In synthesis of the dimers UpU and UpG, with a
      coupling time of 5 min, the dimethoxytrityl cation assay indicated coupling
      yields of > 98%.

PMID- 8532532
TI  - MatInd and MatInspector: new fast and versatile tools for detection of consensus
      matches in nucleotide sequence data.
AB  - The identification of potential regulatory motifs in new sequence data is
      increasingly important for experimental design. Those motifs are commonly located
      by matches to IUPAC strings derived from consensus sequences. Although this
      method is simple and widely used, a major drawback of IUPAC strings is that they
      necessarily remove much of the information originally present in the set of
      sequences. Nucleotide distribution matrices retain most of the information and
      are thus better suited to evaluate new potential sites. However, sufficiently
      large libraries of pre-compiled matrices are a prerequisite for practical
      application of any matrix-based approach and are just beginning to emerge. Here
      we present a set of tools for molecular biologists that allows generation of new
      matrices and detection of potential sequence matches by automatic searches with a
      library of pre-compiled matrices. We also supply a large library (> 200) of
      transcription factor binding site matrices that has been compiled on the basis of
      published matrices as well as entries from the TRANSFAC database, with emphasis
      on sequences with experimentally verified binding capacity. Our search method
      includes position weighting of the matrices based on the information content of
      individual positions and calculates a relative matrix similarity. We show several
      examples suggesting that this matrix similarity is useful in estimating the
      functional potential of matrix matches and thus provides a valuable basis for
      designing appropriate experiments.

PMID- 8532533
TI  - mRNA decay in spinach chloroplasts: psbA mRNA degradation is initiated by
      endonucleolytic cleavages within the coding region.
AB  - The expression of chloroplast genes during leaf development in higher plants is
      regulated on several levels as transcription, RNA processing and stability,
      protein stability and turnover. Differential mRNA stability is one major
      component which contributes to the developmentally controlled accumulation of
      higher plant chloroplast psbA mRNA, which encodes the D1 protein of photosystem
      II. To understand the molecular mechanisms of specific mRNA degradation an in
      vitro mRNA decay system based on lysed chloroplasts from spinach leaves was
      established. Employing this degradation extract the decay of psbA mRNA was
      analyzed. Half-life of the psbA mRNA in vitro is dependent on the degradation
      conditions as the presence of Mg2+, which was found to stabilize the mRNA.
      Addition of tRNA stabilizes the mRNA and allows the accumulation of distinct
      degradation intermediates. psbA mRNA derived fragments of the same size were
      detected in degradation experiments in vitro, in organello and in vivo. 5' ends
      of the degradation intermediates were identified by primer extension and found to
      be localized in the 5' part of the coding region. The data indicate a degradation
      mechanism involving initiation of psbA mRNA decay by specific endonucleolytic
      cleavage and subsequent exonucleolytic degradation of the fragments. Possible
      models for cleavage site recognition are discussed.

PMID- 8532534
TI  - Construction of trypanosome artificial mini-chromosomes.
AB  - We report the preparation of two linear constructs which, when transformed into
      the procyclic form of Trypanosoma brucei, become stably inherited artificial mini
      chromosomes. Both of the two constructs, one of 10 kb and the other of 13 kb,
      contain a T.brucei PARP promoter driving a chloramphenicol acetyltransferase
      (CAT) gene. In the 10 kb construct the CAT gene is followed by one hygromycin
      phosphotransferase (Hph) gene, and in the 13 kb construct the CAT gene is
      followed by three tandemly linked Hph genes. At each end of these linear
      molecules are telomere repeats and subtelomeric sequences. Electroporation of
      these linear DNA constructs into the procyclic form of T.brucei generated
      hygromycin-B resistant cell lines. In these cell lines, the input DNA remained
      linear and bounded by the telomere ends, but it increased in size. In the cell
      lines generated by the 10 kb construct, the input DNA increased in size to 20-50
      kb. In the cell lines generated by the 13 kb constructs, two sizes of linear DNAs
      containing the input plasmid were detected: one of 40-50 kb and the other of 150
      kb. The increase in size was not the result of in vivo tandem repetitions of the
      input plasmid, but represented the addition of new sequences. These Hph
      containing linear DNA molecules were maintained stably in cell lines for at least
      20 generations in the absence of drug selection and were subsequently referred to
      as trypanosome artificial mini-chromosomes, or TACs.

PMID- 8532535
TI  - DNA binding properties of the Saccharomyces cerevisiae DAT1 gene product.
AB  - The DAT1 gene of Saccharomyces cerevisiae encodes a DNA binding protein (Dat1p)
      that specifically recognizes the minor groove of non-alternating
      oligo(A).oligo(T) tracts. Sequence-specific recognition requires arginine
      residues found within three perfectly repeated pentads (G-R-K-P-G) of the Dat1p
      DNA binding domain [Reardon, B. J., Winters, R. S., Gordon, D., and Winter, E.
      (1993) Proc. Natl. Acad. Sci. USA 90, 11327-1131]. This report describes a rapid
      and simple method for purifying the Dat1p DNA binding domain and the biochemical
      characterization of its interaction with oligo(A).oligo(T) tracts.
      Oligonucleotide binding experiments and the characterization of yeast genomic
      Dat1p binding sites show that Dat1p specifically binds to any 11 base sequence in
      which 10 bases conform to an oligo(A).oligo(T) tract. Binding studies of
      different sized Dat1p derivatives show that the Dat1p DNA binding domain can
      function as a monomer. Competition DNA binding assays using poly(I).poly(C),
      demonstrate that the minor groove oligo(A).oligo(T) constituents are not
      sufficient for high specificity DNA binding. These data constrain the possible
      models for Dat1p/oligo(A).oligo(T) complexes, suggest that the DNA binding domain
      is in an extended structure when complexed to its cognate DNA, and show that
      Dat1p binding sites are more prevalent than previously thought.

PMID- 8532536
TI  - Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger
      protein in human osteoblasts.
AB  - The TGF-beta family of growth factors has been extensively studied and found to
      play major roles in bone physiology and disease. A novel, TGF-beta-inducible
      early gene (TIEG) in normal human fetal osteoblasts (hFOB) has been identified
      using differential-display PCR. Using this differentially expressed cDNA fragment
      of TIEG to screen a hOB cDNA library, a near full-length cDNA for this gene was
      isolated. Northern analyses indicated that the steady-state levels of the 3.5 kb
      TIEG mRNA increased within 30 min of TGF-beta treatment of human osteoblasts and
      reached a maximum of 10-fold above control levels at 120 min post-treatment. This
      regulation was independent of new protein synthesis. Computer sequence analyses
      indicates that TIEG mRNA encodes for a 480 amino-acid protein. The TIEG protein
      contains three zinc finger motifs, several proline-rich src homology-3 (SH3)
      binding domains at the C-terminal end, and is homologous in this region to the
      zinc finger-containing transcription factor family of genes. A growth
      factor/cytokine-specific induction of TIEG has been shown. TIEG expression in
      hFOB cells was highly induced by TGF-beta and bone morphogenetic protein-2 (BMP
      2), with a moderate induction by epidermal growth factor (EGF), but no induction
      by other growth factors/cytokines was observed. In addition to osteoblastic
      cells, high levels of TIEG expression were detected in skeletal muscle tissue,
      while low or no detectable levels were found in brain, lung, liver or kidney.
      Because TIEG is an early induced putative transcription factor gene, and shows a
      growth factor induction and tissue specificity, its protein product might play an
      important role as a signalling molecule in osteoblastic cells.

PMID- 8532537
TI  - Synthesis and NMR of RNA with selective isotopic enrichment in the bases.
AB  - Efficient syntheses of pyrimidine and purine nucleosides and nucleotides with
      selective 13C enrichment in the base moieties are described. Uridine and cytidine
      are labeled at position C6 and adenosine and guanosine are labeled at position
      C8. The selectively labeled nucleosides were converted to nucleoside
      triphosphates and used with in vitro transcription to synthesize labeled RNA.
      Isotope-edited 12C and 13C sub-spectra of a omega 1-1/2-X-filtered NOESY
      experiment are demonstrated to be useful for making resonance assignments and for
      deriving structural information in large (> 20 nt) RNA molecules. The labeled
      RNAs also allow heteronuclear J-couplings and relaxation parameters to be
      measured without complications from 13C-13C J-couplings.

PMID- 8532538
TI  - Cytosine specific DNA sequencing with hydrogen peroxide.

PMID- 8532539
TI  - A rapid and reliable DNA preparation method for screening a large number of yeast
      clones by polymerase chain reaction.

PMID- 8532540
TI  - Purification of DNA fragments from lyophilized agarose gels.

PMID- 8532541
TI  - A simple and rapid electrophoresis method to detect sequence variation in PCR
      amplified DNA fragments.

PMID- 8532542
TI  - Rapid purification of fluorescent dye-labeled products in a 96-well format for
      high-throughput automated DNA sequencing.

PMID- 8532543
TI  - Selective recovery of DNA fragments from silica particles: effect of A-T content
      and elution conditions.

PMID- 8532544
TI  - Generation of oligonucleotides containing site-specific cyclobutane pyrimidine
      dimers and pyrimidine(6-4)pyrimidinone photoproducts by immunoprecipitation.

PMID- 8532545
TI  - The impact of cancer pain education on family caregivers of elderly patients.
AB  - PURPOSE/OBJECTIVES: To examine the impact of pain education on family members
      providing home care to elderly patients with cancer. DESIGN: Quasiexperimental.
      SETTING: Homes of selected patients from two California medical centers. SAMPLE:
      Fifty family caregivers of patients experiencing cancer-related pain. METHODS:
      The pain education program included three components: pain assessment,
      pharmacologic interventions, and nonpharmacologic interventions. Patients and
      their family caregivers were evaluated prior to initiation of the program and at
      one and three weeks following the interventions. MAIN RESEARCH VARIABLES: Quality
      of life (QOL); knowledge and attitudes about pain; and caregiver burden.
      FINDINGS: Findings based on measures of QOL and caregiver burden demonstrated the
      physical and psychological impact of family caregiving and pain management.
      Comparison between elderly patients with cancer and family caregivers revealed
      the pain experience's significant impact on family members caring for a loved one
      in pain. CONCLUSIONS: The pain education program was effective in improving
      knowledge and attitudes regarding pain management. IMPLICATIONS FOR NURSING
      PRACTICE: Pain management is a priority for nurses, and use of interventions such
      as structured pain education improves QOL outcomes for elderly patients and their
      family caregivers.

PMID- 8532546
TI  - Critical pathway for administering high-dose chemotherapy followed by peripheral
      blood stem cell rescue in the outpatient setting.
AB  - PURPOSE/OBJECTIVES: To explain the rationale and process of outpatient critical
      pathway development for sequential high-dose chemotherapy followed by peripheral
      blood stem cell transplantation. DATA SOURCES: Published books and journal
      articles. DATA SYNTHESIS: Complex treatment for patients with metastatic breast
      cancer is shifting to the outpatient area. To make this therapy safe and cost
      effective, a process for monitoring this type of outpatient care needs to be
      developed. CONCLUSIONS: Collaboration with a multidisciplinary team is important
      in ensuring quality of care for complex outpatient treatment protocols. Critical
      pathway development can serve as a road map for delivering this care.
      IMPLICATIONS FOR NURSING PRACTICE: As team leaders, nurses should oversee the
      critical pathway development and implementation. Nurses also should maintain
      their role of patient advocacy through monitoring pathway compliance.

PMID- 8532547
TI  - Addressing sexual dysfunction following radiation therapy for a gynecologic
      malignancy.
AB  - PURPOSE/OBJECTIVES: To review the aspects of normal sexual response, current
      incidence of sexual dysfunction following radiation therapy for a gynecologic
      malignancy, nursing interventions for each symptom that may occur, and nursing
      research priorities. DATA SOURCES: Published articles, book chapters, American
      Cancer Society materials, healthcare professionals working in the field of
      radiation oncology, and patients. DATA SYNTHESIS: Radiation therapy frequently is
      the treatment of choice for a gynecologic malignancy. High-dose radiation to the
      pelvis causes varying degrees of sexual dysfunction because of its effects on the
      ovaries and vagina. CONCLUSIONS: Sexual dysfunction resulting from the effects of
      radiation therapy on the ovaries and vagina can be prevented, minimized, or
      managed when the nurse is aware of the needs, desires, and expectations of
      patients receiving this treatment. IMPLICATIONS FOR NURSING PRACTICE: Sexuality
      is an important aspect of quality of life that most healthcare professionals do
      not address. Nursing assessment and practical care strategies for sexual
      dysfunction can be implemented. Additional nursing research on this subject is
      warranted.

PMID- 8532548
TI  - Differences in pain knowledge and perception of the pain experience between
      outpatients with cancer and their family caregivers.
AB  - PURPOSE/OBJECTIVES: To determine if knowledge about pain and the perception of
      the pain experience differ when comparing outpatients experiencing cancer-related
      pain with their family caregivers. DESIGN: Quantitative, descriptive. SETTING:
      Sixteen oncology outpatient settings that are part of the Oncology Nursing
      Research Network. SAMPLE: Eighty-six outpatients with cancer-related pain and
      their family caregivers. METHODS: Patients and their family caregivers were
      recruited in the outpatient setting and asked to complete a demographic
      questionnaire and the Pain Experience Scale. The patients also were asked to
      complete the Karnofsky Performance Scale. MAIN RESEARCH VARIABLES: Patients' and
      their family caregivers' knowledge about pain and their perception of the pain
      experience. FINDINGS: No significant differences in knowledge scores were found
      between the patients and their family caregivers. A significant difference in the
      perception of the pain experience was found, with the family caregivers viewing
      the experience more negatively than the patients did. Family caregivers reported
      that (a) patients had significantly higher levels of pain compared to patient
      reports, (b) patients experienced significantly greater distress from their pain
      than the patients reported for themselves, and (c) family caregivers experienced
      significantly greater distress from the patients' pain than the patients reported
      for their caregiver. CONCLUSIONS: Outpatients with cancer and their family
      caregivers possess limited knowledge about pain and pain management and perceive
      the pain experience differently. IMPLICATIONS FOR NURSING PRACTICE: Outpatients
      and their family caregivers need to be better educated about how to manage cancer
      related pain. In addition, to reduce patient and caregiver distress, oncology
      nurses need to facilitate communication between patients and family caregivers
      about the pain experience.

PMID- 8532549
TI  - Nurses' perceptions of antiemetic effectiveness.
AB  - PURPOSES: To determine which antiemetics are being used with ondansetron (Zofran,
      Cerenex Pharmaceuticals, Research Triangle Park, NC) for patients receiving
      emetogenic chemotherapy, identify the more frequently administered antiemetic
      regimens, and ascertain nurses' perceptions of the effectiveness of these
      regimens. DESIGN: Descriptive survey. SETTING: Continental United States. SAMPLE:
      A random sample (N = 962) of Oncology Nursing Society members who designate
      themselves as practicing in the area of chemotherapy. METHODS: The Antiemetic
      Drug(s)/Drug Combination(s) Inventory, an open-ended questionnaire soliciting
      information on first- and second-line antiemetic regimens for emetogenic
      chemotherapy protocols, was mailed to 5,950 oncology nurses. Descriptive
      statistics and nondistributive analysis were used to analyze the data. FINDINGS:
      Ondansetron was used in 7 of 10 antiemetic regimens, which accounted for 50% of
      the most frequently used regimens. Nurses rated first-line antiemetic
      combinations as highly effective. Ondansetron alone was ranked as the seventh
      most effective first-line antiemetic for cisplatin protocols and fifth for
      noncisplatin protocols. Nurses noted limitations of ondansetron use, which
      included delayed nausea and vomiting and the drug's high cost. CONCLUSIONS: Study
      participants indicated that a variety of drugs were used in antiemetic regimens.
      Ondansetron use has improved the control of post-chemotherapy nausea, vomiting,
      and retching. IMPLICATIONS FOR NURSING PRACTICE: Antiemetics are administered
      regularly in the hospital and home to decrease chemotherapy-related nausea,
      vomiting, and retching. Managing these side-effects requires superior assessment
      skills and extensive knowledge of pharmacologic actions. Patient and family
      education on antiemetics is essential in light of increased administration of
      outpatient chemotherapy.

PMID- 8532550
TI  - Digital rectal examinations and prostate cancer screening: attitudes of African
      American men.
AB  - PURPOSE/OBJECTIVES: To explore the relationship between attitudes toward digital
      rectal examination (DRE) and participation in prostate cancer screening among
      African American men. DESIGN: Survey. SETTING: Prostate cancer screenings with a
      prostate-specific antigen (PSA) blood test held at churches with African American
      members in Detroit, MI. SAMPLE: 613 African American men between the ages of 40
      and 70. METHODS: Self-administered, structured questionnaires examining attitudes
      toward DRE, past experiences with DRE, and fear of cancer. MAIN OUTCOME MEASURES:
      Willingness to undergo DRE. FINDINGS: The majority of men who were screened had
      positive attitudes about DRE. Fear of cancer was associated with negative
      attitudes toward DRE. DREs were not a deterrent among men who attended the
      screenings. CONCLUSION: Negative attitudes toward DRE do not necessarily deter
      African American men from participating in prostate cancer screenings.
      IMPLICATIONS FOR NURSING PRACTICE: Prostate cancer screening programs should
      attempt to use both DRE and PSA. More reliable prostate cancer indicators are
      obtained by incorporating DRE with PSA tests.

PMID- 8532551
TI  - The impact of mailing fecal occult blood test kits on return rate in a community
      cancer screening center.
AB  - PURPOSE/OBJECTIVES: To describe how mailing fecal occult blood test (FOBT) kits
      prior to office appointments rather than distributing the kits at office visits
      affects the return rate of completed tests and to describe the demographic
      characteristics of those who returned the tests and those who did not. DESIGN:
      Retrospective chart review. SETTING: An urban, community hospital cancer
      screening program. SAMPLE: 631 people; 382 returned the FOBTs; 128 did not return
      the tests; 121 refused all colorectal screening including fecal occult blood
      testing. METHODS: Charts were reviewed and abstracted using a form; data were
      entered and analyzed using descriptive statistics. MAIN RESEARCH VARIABLES:
      Completion and return of the FOBT and FOBT results. FINDINGS: The return rate
      when the FOBT was mailed prior to appointments was 85% compared to 32% for
      patients who received test kits in the office. Of those who completed the test,
      80% also underwent digital rectal examinations and 26% underwent flexible
      sigmoidoscopies. Nine people demonstrated positive FOBT results, but no
      colorectal cancers were detected. CONCLUSIONS: In this retrospective chart
      review, mailing FOBT kits prior to office appointments appeared to be related to
      increased return rates. IMPLICATIONS FOR NURSING PRACTICE: Findings are
      preliminary in nature, but nurses must consider various methods of distributing
      FOBTs in order to increase return rates.

PMID- 8532552
TI  - Relationship of perceived barriers to breast self-examination in women of varying
      ages and levels of education.
AB  - PURPOSE/OBJECTIVES: To examine perceived barriers to performing breast self
      examination (BSE) in women of varying age groups and education levels and
      investigate the relationship of age and education to frequency of BSE. DESIGN:
      Descriptive, retrospective. SETTING: A university nursing center and clerical
      offices. SAMPLE: Convenience sample of 374 women. METHOD: Subjects were asked to
      complete Champion's Health Belief Model questionnaire. MAIN RESEARCH VARIABLE:
      Barriers to BSE practice. FINDINGS: Chi-squares analyses comparing age and
      education levels to BSE frequency showed no significant differences among groups.
      Cross tabulations suggested that differences in perception of individual barriers
      to practice may exist among women of different age groups and education levels.
      CONCLUSION: Women of varying age groups and education levels responded to
      individual barrier items differently. IMPLICATIONS FOR NURSING PRACTICE: Young
      women may need help developing confidence in their BSE technique as well as
      accurate information to reduce their fears about BSE. Middle-aged women also need
      this information to reduce their fears and may need help in developing a reminder
      method for practicing BSE. Older women may benefit from education about BSE's
      value to them. Less educated women may need information to reduce fear, while
      women at higher education levels may benefit from help in developing a reminder
      method.

PMID- 8532553
TI  - Assessing master's programs in oncology nursing.

PMID- 8532554
TI  - Relieving xerostomia from radiation therapy.

PMID- 8532555
TI  - Cryotherapy reduces fluorouracil-related side effects.

PMID- 8532556
TI  - Diarrhea in patients receiving enteral nutrition.

PMID- 8532557
TI  - New care model shifts accountability from manager to staff nurses.

PMID- 8532558
TI  - Support group thrives.

PMID- 8532559
TI  - Maintaining cultural awareness when caring for patients.

PMID- 8532560
TI  - Patient experiences adverse drug reaction to etoposide for adenocarcinoma of the
      lung.

PMID- 8532561
TI  - The chain of survival and EMS-C.

PMID- 8532562
TI  - Teaching emergency medicine to pediatric residents: a national survey and
      proposed model.
AB  - To assess how emergency medicine is taught to pediatric residents, a cross
      sectional survey was performed using a written questionnaire distributed to the
      chief residents of accredited pediatric residency programs throughout the
      continental United States. Information requested included the demographics of the
      training program, the structure of the emergency department (ED) rotation, and
      the chief residents' perceptions of the quality of precepting in the ED. Eighty
      three percent of 149 institutions responded. The mean number of pediatric
      patients/year is 21,241 (range 500-100,000), supplying approximately 500 to 700
      patients/resident/year. A freestanding pediatric ED serves as the main training
      site in 50% of programs, and 3% do not use an ED at all. Case-by-case, one-on-one
      precepting occurs in 91% of EDs. Precepting is performed mostly by pediatric
      attendings (74%) and general emergency medicine attendings (38%). Seventy-four
      percent of programs provide a formal orientation, and 88% provide end-rotation
      evaluations. Twenty-two percent of the chief residents consider their pediatric
      ED rotation as "average" when compared with the case-by-case precepting delivered
      in other hospital rotations; 39% consider the ED rotation as "above average," and
      33% as "below average." Programs with core lecture series, skills workshops, and
      formal orientation and evaluation procedures are more likely to be regarded as
      "above average." Pediatric emergency medicine rotations provide ample opportunity
      for case-by-case precepting. Programs with an established curriculum and
      pediatric attending presence are more likely to be successful in this regard. The
      full potential of the ED rotation can be realized through faculty training in
      precepting and evaluation methods.

PMID- 8532563
TI  - Urethral prolapse: an often misdiagnosed cause of urogenital bleeding in girls.
AB  - Urethral prolapse is an uncommon disorder in girls, usually presenting as
      "vaginal" bleeding. This retrospective chart review focuses on the high rate of
      misdiagnosis of urethral prolapse and describes treatment modalities based on 24
      patients seen at a major children's hospital during an 11-year span. Their mean
      age was 4.9 years. The initial diagnosis, made by the referring pediatrician or
      emergency physician, was correct in only five girls (21%). Twenty children
      presented with urogenital bleeding. Operative correction was employed as initial
      treatment in 16 girls, with one recurrence. The remaining eight children were
      treated nonoperatively. Of these, five showed no improvement and underwent
      surgical repair. Although most children eventually require resection of the
      prolapsed urethral mucosa, nonoperative treatment is appropriate for asymptomatic
      girls with a mild degree of urethral prolapse. Increased physician awareness of
      urethral prolapse is desirable to enhance early recognition and to avoid
      unnecessary examinations and parental concern.

PMID- 8532564
TI  - Soft tissue swelling with fractures: abuse versus nonintentional.
AB  - The objectives were to 1) define the amount of postfracture swelling at
      presentation in long bone fractures, and 2) to study the relationship between
      suspected abuse and/or neglect (A/N) and degree of postfracture swelling at
      presentation. This was a prospective study of 37 patients less than 11 years of
      age presenting with long bone fractures to the emergency department (ED) of the
      Children's Hospital of Michigan between August 1992 and December 1992. Data were
      recorded at the time of the ED visit and from medical records which were reviewed
      four to six months later. Of the patients enrolled in the study, eight were
      categorized as A/N and 29 as nonintentional. There was no difference in reported
      injury age between the two groups (15.5 +/- 24.5 hours vs 14.0 +/- 17.7, P =
      0.8). At presentation the mean increase in circumference from post-fracture
      swelling was 9.6 +/- 7.1%, using the uninjured extremity as the control. The
      abuse group had a lesser increase in circumference compared to the nonintentional
      group, even after adjusting for injury age (3.8 +/- 3.6% vs 11.2 +/- 7.0%, P <
      0.006). We concluded that patients with long bone fractures had a mean swelling
      of 9.6 +/- 7.1% at presentation. Injuries induced by A/N present with less
      swelling than similar injuries sustained nonintentionally, and we speculate that
      this difference indicates that the history and/or time of injury may not be
      reliable.

PMID- 8532565
TI  - Prehospital management of pediatric asthma requiring hospitalization.
AB  - Our objective was to evaluate the quality of prehospital assessment and
      management in pediatric asthma requiring hospitalization via a retrospective
      chart review. Charts were obtained from a pediatric emergency department (ED)
      with 24,000 annual visits. Included in the study were 27 patients less than 18
      years of age with asthma requiring hospitalization, transported to the Boston
      City Hospital Pediatric ED by Boston Emergency Medicine Services (EMS). We found
      that 12 patients admitted to the pediatric intensive care unit over an 18-month
      period, and 15 patients admitted to the ward over a six-month period, received
      prehospital care from Boston EMS. Only 63% of cases (17/27) had a physical
      examination marker of asthma severity noted on the EMS record. Twenty-six percent
      of cases (7/27) did not receive O2 in the field. Thirty percent of cases (8/27)
      were hypoxic at ED presentation. None of the hypoxic patients had received
      albuterol in the field, and one did not receive O2. We conclude that further
      study of the prehospital assessment and management of pediatric asthma is
      warranted.

PMID- 8532566
TI  - Security in pediatric emergency departments.
AB  - With increasing emergency department (ED) violence, security in pediatric EDs is
      an important concern. The objective of this study was to document current
      security measures taken in pediatric EDs in the United States. A telephone survey
      of the security director or designee in the 42 children's hospitals in the United
      States with over 150 beds was performed. A questionnaire focusing on ED security
      was administered. Two hospitals declined to participate. In 62.5% of EDs
      surveyed, a security officer is present in the ED 24 hours/day. Hospital security
      officers carry firearms in 32.5% of hospitals surveyed. Most (92.5%) EDs have an
      alarm system or "panic button" which alerts central security; but only 15% have a
      direct phone from the ED to security. Seven EDs (17.5%) use bullet-resistant
      glass, and 14 EDs (35%) have controlled access. No ED reported universal metal
      detector screening. Fourteen directors (35%) reported having had a firearm
      related incident in their ED in the past year. In spite of the relatively common
      nature of ED violence, security measures in pediatric EDs are varied, with most
      EDs not using all measures recommended by the American College of Emergency
      Physicians.

PMID- 8532567
TI  - The relationship between grandmothers' involvement in child care and emergency
      department utilization.
AB  - This study examines the relationship between involvement of grandmothers in child
      care and poor urban mothers' use of the emergency department (ED) for nonurgent
      care. Mothers with an index child between one and two years old were interviewed
      in the waiting room of a pediatric continuity clinic. They were asked about the
      proximity and involvement in child care of a grandmother, great-grandmother, or
      female family member. Frequency of ED use was abstracted from the index child's
      medical records. Results showed that mothers who frequently used the ED for
      nonemergent pediatric care were more likely to have the child's grandmother or
      great-grandmother living in close proximity or involved in care of the child than
      infrequent users (80 vs 45%, P < 0.05). This study suggests that proximity and
      involvement of the grandmother may influence health care decisions.

PMID- 8532568
TI  - Cerebrospinal fluid analysis in children with seizures.
AB  - Cerebrospinal fluid (CSF) examinations of 212 children aged two to 24 months with
      idiopathic nonfebrile seizures, complex febrile seizures, or status epilepticus,
      who had a lumbar puncture within 24 hours of the convulsion, were reviewed to
      determine whether an idiopathic convulsion can result in CSF abnormalities.
      Children with complex febrile seizures had a median CSF white blood cell count of
      1 cell/mm3 (range 0-19 cells/mm3) and a median CSF polymorphonuclear (PMN) cell
      count of 0 cells/mm3 (range 0-8 cells/mm3). The CSF white blood cell (WBC) count
      was elevated above the upper limit of normal of 5 cells/mm3 in 9.8% and the
      absolute number of polymorphonuclear cells was more than 0 cells/mm3 in 26.2% of
      the complex febrile seizure subjects. Values at the 95th percentile were
      calculated; a total of 8 WBC/mm,3 4 PMN/mm,3 protein of 73 mg/dl and glucose of
      119 mg/dl determined the 95th percentile CSF values for the patients with complex
      febrile seizures. Patients with nonfebrile seizures or with status epilepticus
      had similar findings. We conclude that complex febrile, idiopathic nonfebrile
      convulsions or status epilepticus may affect CSF findings in children: CSF with >
      20 WBC/mm3 or > 10 PMN/mm3 should not be attributed to seizures.

PMID- 8532569
TI  - Perforation of the colon in an adolescent girl.
AB  - We report a case of a 13-year-old girl who presented with acute abdominal pain
      secondary to a sigmoid colon perforation. History, physical examination, and
      laboratory and radiographic studies were all suggestive, though not diagnostic,
      of an abdominal catastrophe. Her father died at the age of 30 from complications
      of bowel perforations and a vascular aneurysm. The unusual operative findings in
      our patient, together with her father's medical history, lead to the underlying
      diagnosis of Ehlers-Danlos syndrome. Knowledge of this family history at the time
      of presentation could have aided in diagnosis. Clinical manifestations and
      etiology of Ehlers-Danlos syndrome are discussed.

PMID- 8532570
TI  - Hypothermia in shaken infant syndrome.

PMID- 8532571
TI  - Cyproheptadine-induced central anticholinergic syndrome in a child: a case
      report.
AB  - A 16-year-old female patient presented to our emergency department with
      anticholinergic psychosis after an ingestion of cyproheptadine. The central
      anticholinergic syndrome occurs frequently but often goes unrecognized because
      many patients do not fit into a well defined clinical pattern. The diagnosis
      depends on the suspicion and recognition of the psychiatric manifestations,
      including agitation, confusion, and hallucinations. A high index of suspicion is
      necessary in children in particular, since central effects seem to predominate in
      many anticholinergic overdoses.

PMID- 8532572
TI  - Ventricular fibrillation following adenosine therapy for supraventricular
      tachycardia in a neonate with concealed Wolff-Parkinson-White syndrome treated
      with digoxin.

PMID- 8532573
TI  - Children with asthma in the emergency department: spectrum of disease, variation
      with ethnicity, and approach to treatment.
AB  - The role of the pediatric emergency department (ED) in the management of acute
      asthma was assessed by examining patterns of referrals, admissions, clinical
      patient evaluation, laboratory tests ordered, and treatment instituted. The
      functioning of the attending physicians with different degrees of seniority was
      also evaluated. One thousand thirty-six children with acute asthma (5.3% of all
      visits) were admitted to the ED during 1990. The mean age was 5.5 years, and the
      male to female ratio was 2.6:1. Fifty percent of the patients reported atopic
      disease in their immediate family, and upper respiratory tract infection
      preceding the attack was reported in 27% of patients. Significant differences
      were observed between Arab and Jewish patients: more Arab patients presented
      after physician referral (90 vs 33%) in morning hours (43 vs 26%), and after a
      longer duration of symptoms. Experienced physicians ordered fewer laboratory
      tests and treated the patients less aggressively than junior physicians. Patients
      treated by senior physicians stayed less time in the ED, and a smaller proportion
      of patients was hospitalized (4 vs 19%). Patients admitted by senior physicians
      had a longer period of hospitalization (4.7 vs 1.2 days). This study shows that
      ethnicity influenced the pattern of utilization of the ED and that the approach
      to care differed among junior and senior physicians.

PMID- 8532574
TI  - Unwinding the COBRA: new perspectives on EMTALA.

PMID- 8532575
TI  - Recent onset seizures in infant.

PMID- 8532576
TI  - The needle-wire-dilator technique for the insertion of chest tubes in pediatric
      patients.
AB  - We evaluated the needle-wire-dilator (NWD) technique, using commercially
      available sets, for insertion of chest tubes in 24 pediatric patients who were
      admitted to our pediatric intensive care unit (PICU). Fourteen patients had
      pneumothoraces, three had hemothoraces, two had pneumonia with empyema, four had
      pleural transudate effusions, and one had chylothorax. The ages of the patients
      ranged from four months to 24 years, and the sizes of the inserted chest tubes
      ranged from 10F to 20F. All insertions were successful, and the time from
      invasion of the pleural space by the needle to completion of chest tube insertion
      and connection to the tubing drainage system ranged from four to seven minutes.
      In four patients the procedure had to be performed while a significant
      coagulopathy existed. However, none of the 24 patients developed hemorrhagic
      complications. The only complication observed was a kink in the chest tube in
      five patients, resulting in recurrence of pneumothorax in four and pleural
      effusion in one. These adverse occurrences were corrected by repositioning the
      chest tubes in three patients, and by replacing the chest tubes with the stiffer,
      trochar type, chest tubes in the other two. We conclude that the NWD technique
      for chest tube insertion is quick, safe, and easy to perform in all pediatric age
      groups. The commercially available chest tubes used in our study were somewhat
      softer than the trochar type chest tubes available, which explains the occurrence
      of kinks in some of them.

PMID- 8532577
TI  - Emergency versus casual pediatric emergency medicine.

PMID- 8532578
TI  - Pediatric emergency medicine: legal briefs.

PMID- 8532579
TI  - Polle's syndrome (Munchausen by proxy)

PMID- 8532580
TI  - The trefoil peptides spasmolytic polypeptide and intestinal trefoil factor are
      major secretory products of the rat gut.
AB  - Spasmolytic polypeptide (SP) and intestinal trefoil factor (ITF) are trefoil
      peptides expressed by gut mucus cells. Using specific antisera we have quantified
      and characterized the molecular forms and distribution of these peptides in the
      rat gut. SP predominates in the gastric antrum as a 12 kDa form. ITF (7 kDa) is
      highly expressed throughout the small intestine. Both peptides are distributed in
      the apical secretory compartment of antral mucus cells (SP) and goblet cells
      (ITF), and on the lumenal surface. This study quantifies SP and ITF for the first
      time, and confirms them as major secretory products of the rat gut.

PMID- 8532581
TI  - Structural and biosynthetic properties of peptides in cone snail venoms.
AB  - Venoms of the predatory cone snails Conus textile, Conus striatus, and Conus
      magus were subjected to comprehensive analysis of peptide content. With the fish
      eating cone snails C. magus and C. striatus, the most abundant venom peptides
      were of > 30-50 residues, whereas the predominant peptides in the venom of the
      mollusc-eating snail, C. textile, were of 20-35 residues. Amino acid sequencing
      revealed an identical but unusual amino acid in a conserved position in four
      novel omega-type peptides from the C. textile venom. Two conserved amino acid
      sequences were obtained from the venoms of both C. magus and C. striatus. The
      amino acid compositions of the isolated C. textile peptides and the expected
      processing products of the propeptides (42) were compared. Despite the recovery
      in abundance of the carboxyl-terminal omega-type peptides, none of the isolated
      peptides had compositions expected from the propeptide amino-terminal fragments.
      We conclude that there are likely mechanisms for excluding the amino-terminal
      propeptide fragments from this venom, resulting in a venom with greater potency.
      Amounts of the different omega-type peptides in the venom vary widely, suggesting
      a distinct mechanism that results in the selective synthesis of different
      bioactive carboxyl-terminal propeptide fragments at elevated levels.

PMID- 8532582
TI  - beta-Amyloid peptide, substance P, and SEC receptor ligand activate cytoplasmic
      Ca2+ in neutrophil-like HL-60 cells: effect of chemotactic peptide antagonist
      BocMLF.
AB  - It has been reported that a discrete peptide fragment of beta-amyloid protein,
      beta A(25-35), and neuropeptide substance P (SP) possessed sequence homology and
      could bind to the serine protease inhibitor (serpin) enzyme complex (SEC)
      receptor. Thus, it has been thought that these peptides and SEC receptor ligand
      might have similar biological activities. In the present study, we found that C
      terminal amidated beta A(25-35)-NH2, SP, and the SEC receptor ligand, Phe-Val-Phe
      Leu-Met(FVFLM), could induce an increase in the intracellular free Ca2+
      concentration ([Ca2+]i) in neutrophil-like human leukemic (HL-60) cells.
      Pretreatment with pertussis toxin (PTX) potently inhibited the increase in
      [Ca2+]i stimulated by these peptides, suggesting that these responses might be
      mediated by PTX-sensitive G-proteins. Furthermore, we examined the effect on
      these responses of t-butyloxycarbonyl-methionyl-leucyl-phenylalanine (BocMLF),
      which is a competitive antagonist of chemotactic peptide N-formyl-methionyl
      leucyl-phenylalanine (fMLF) at its receptor. BocMLF scarcely inhibited the
      [Ca2+]i increase stimulated by beta A(25-35)-NH2. However, the increase in FVFLM
      induced [Ca2+]i was potently inhibited by BocMLF. The results suggest that the
      [Ca2+]i activation of beta A(25-35)-NH2 may have a different mechanism from that
      of FVFLM in neutrophil-like HL-60 cells, which is not mediated by the SEC
      receptor.

PMID- 8532583
TI  - Characterization of cholecystokinin receptors in canine intestinal circular
      muscle.
AB  - We localized and characterized the binding of [3H](+/-)-L364,718 in canine small
      intestine circular muscle. The highest densities of [3H]L364,718 binding were
      located in the fraction enriched in deep muscular plexus synaptosomal membranes.
      In this fraction [3H]L364,718 binding was of high density (Bmax 136.78 +/- 53.66
      fmol/mg) and high affinity (Kd 1.67 +/- 0.74 nM). Kinetics studies revealed that
      binding was reversible and yielded a similar Kd value. L364,718, CCK-8-S, and
      L365,260 fully displaced [3H]L364,718 binding, but ligands at CCKB receptors,
      gastrin-17, and YM022 did not. Therefore, CCKA receptors in canine intestine
      circular muscle are located on nerve endings.

PMID- 8532584
TI  - Expression and characterization of a recombinant human parathyroid hormone
      partial agonist with antagonistic properties: Gly-hPTH(-1-->+84).
AB  - We have produced and characterized a hPTH analogue with an amino-terminal
      extension of glycine, Gly-hPTH(-1-->+84) (denoted Gly-hPTH). The hormone analogue
      was synthesized in E. coli strain BJ5183 transformed with the expression plasmid
      pKKPTH, extracted from the bacterial pellet and purified by reverse-phase high
      performance liquid chromatography. Its chemical nature, as determined by amino
      acid composition analysis, N-terminal amino acid analysis, and mass spectrometry,
      showed the 9480-Da Gly-hPTH as the predominant species. Because f-Met-Gly-hPTH
      was the expected form encoded by the plasmid construct, the results indicate that
      the f-Met residue was efficiently removed from the precurser form. The following
      functional characteristics of Gly-hPTH were demonstrated. 1) In cells transfected
      with the human PTH/PTHrP receptor, the receptor binding affinity was reduced
      threefold compared to the authentic hPTH(1-84) produced by Saccharomyces
      cerevisiae (apparent Kds: 8.4 and 2.7 nM, respectively). 2) Using the same cells,
      Gly-hPTH showed 27-fold reduced potency compared to hPTH(1-84) in stimulating
      intracellular cAMP production (EC50: 32 and 1.2 nM, respectively). 3) Gly-hPTH
      demonstrated antagonist activity by reducing hPTH-induced cAMP production by 33
      +/- 5% (mean +/- SD) when tested at a 1:1 molar ratio. In these studies the
      recombinant authentic hPTH(1-84) was used as standard for comparisons, and it
      showed an equal receptor binding affinity and cAMP production as the chemically
      synthesized peptide [Nle8,18,Tyr34]bovinePTH(1-34)-NH2.

PMID- 8532585
TI  - Effect of hypophysectomy on pituitary adenylate cyclase-activating polypeptide
      gene expression in the rat testis.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the
      secretin/glucagon/vasoactive intestinal peptide (VIP) family. Our
      immunohistochemical and in situ hybridization histochemical studies indicated
      that PACAP-like immunoreactivity (PACAP-LI) and its mRNA were present in the germ
      cells in the rat testis. Because the testicular function is regulated by the
      pituitary gonadotropins, effect of hypophysectomy on the PACAP gene expression
      was investigated in the rat testis as an attempt to reveal the regulation of the
      testicular PACAP by the pituitary. The levels of testicular PACAP mRNA, which
      were determined by RNase protection assay, increased 2 weeks after
      hypophysectomy. In contrast, the levels of radioimmunoassayable PACAP decreased 2
      weeks after the surgery. Immunohistochemistry showed that hypophysectomy did not
      change the distribution of PACAP-LI, although the number of immunopositive cells
      was markedly reduced after hypophysectomy. The replacement treatments of
      hypophysectomized animals with FSH or LH+FSH restored testicular PACAP mRNA to
      the levels in the control animals. On the other hand, all of these treatments
      (testosterone, LH, FSH, or LH+FSH) significantly increased radioimmunoassayable
      PACAP in the hypophysectomized rat testis. The results suggest that both
      testicular PACAP and its mRNA expression are regulated by the hypothalamic
      pituitary-gonadal activity, and that FSH may play a major role in this
      regulation.

PMID- 8532586
TI  - Immunohistochemical localization of pituitary adenylate cyclase-activating
      polypeptide (PACAP) in the adrenal medulla of the rat.
AB  - Localization of PACAP in rat adrenal glands was examined by light and electron
      microscopic immunohistochemistry using a specific antiserum to PACAP 38, R0831.
      In the light microscopic study, PACAP immunoreactivity was observed in some cell
      groups in the medulla, but not in the cortex. In comparison with adjacent
      sections stained with antisera to catecholamine synthesizing enzymes, PACAP
      positive cells were immunoreactive to tyrosine hydroxylase and dopamine beta
      hydroxylase, but not to phenylethanolamine-N-methyltransferase, suggesting that
      they were coincident with noradrenaline secreting cells. In the electron
      microscopic study using the ABC method, DAB reaction products were diffusely
      distributed in the cytoplasmic matrix of PACAP-positive cells, without intense
      accumulation on the secretory granules. The splanchnic nerve terminals were PACAP
      negative. In postembedding immunohistochemistry, gold particles were localized
      diffusely in the cytoplasma, but not aggregated on the secretory granules. It was
      suggested that PACAP would localize in the cytoplasmic matrix of noradrenaline
      cells and stimulate the catecholamine synthesis and release in the adrenal
      medulla.

PMID- 8532587
TI  - Effect of PACAP on gastric acid secretion in rats.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new VIP-like
      brain-gut peptide. Its effects on the motility and secretory functions of the
      gastrointestinal system have been shown in previous studies. In this study we
      investigated the effect of intravenous PACAP on gastric acid secretion in
      conscious pylorus-ligated rats and in gastric fistula rats. PACAP showed
      significant inhibitory effects on pentagastrin- and histamine-stimulated gastric
      acid secretion, but no effect on basal or carbachol-stimulated secretion in
      pylorus-ligated rats. It did show dose-related inhibitory effects both on basal
      gastric acid secretion and on secretion stimulated by pentagastrin, histamine, or
      carbachol in gastric fistula rats. PACAP did not alter serum gastrin levels.
      Inhibition of prostaglandin synthesis with indomethacin and immunoneutralization
      of somatostatin with anti-somatostatin serum did not prevent the inhibitory
      effect of PACAP on gastric acid secretion in pylorus-ligated rats. We conclude
      that PACAP most likely has a direct effect on parietal cells and that this effect
      may be mediated, at least partially, by inhibition of the action of histamine on
      parietal cells.

PMID- 8532588
TI  - Pituitary adenylate cyclase-activating peptide (PACAP), a VIP-like peptide, has
      prolonged airway smooth muscle relaxant activity.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP), a widely distributed
      peptide belonging to the vasoactive intestinal peptide (VIP) family of peptides,
      stimulates the accumulation of cyclic adenosine monophosphate (cAMP) in many
      tissues, with greater potency and efficacy than VIP. We report that PACAP-38 was
      one-third as potent and 70% as efficacious as VIP in producing relaxation of
      isolated perifused guinea pig strips, although it was approximately twice as
      effective in stimulating cAMP accumulation. The PACAP-38-induced relaxation,
      however, was five to eight times as prolonged as that of VIP, and its cAMP
      stimulation was also more sustained. The prolonged action of PACAP-38 is probably
      due to its greater resistance to enzymatic degradation. The data suggest that
      airway relaxation is not solely dependent on the total content of cAMP in
      airways. PACAP-38 exhibits properties that may be useful in the management of
      airway constriction.

PMID- 8532590
TI  - Impaired retention by angiotensin II mediated by the AT1 receptor.
AB  - We demonstrated previously that hippocampal dentate gyrus neurons were sensitive
      to angiotensin II (AII) and recently discovered that AII applied directly to the
      dentate gyrus inhibited granule cell long-term potentiation induction and that
      the inhibition is mediated by the AT1 receptor and can be blocked by losartan, a
      specific AT1 antagonist. The purpose of the present study was to examine the
      effects of AII administered directly to the dentate gyrus, 1, 5, 50, 150, and 300
      ng, on the retention of an inhibitory shock avoidance response and to determine
      if the resultant impairment of retention can be blocked by losartan. A total of
      12 groups of rats in three experiments were studied. Three independent
      repetitions of 5 ng AII administered bilaterally to the dentate gyrus demonstrate
      a clear impairment of retention under these experimental conditions and that the
      impairment can be effectively prevented by pretreatment with 20 mg/kg of losartan
      IP.

PMID- 8532589
TI  - Zinc modulation of insulin-like growth factor's effect in osteoblastic MC3T3-E1
      cells.
AB  - Whether the anabolic effect of insulin-like growth factor-I (IGF-I) in
      osteoblastic MC3T3-E1 cells is modulated by zinc, an activator of bone formation,
      was investigated in vitro. After subculture for 3 days, the cells were cultured
      for 72 h with IGF-I (10(-8) M). The peptide produced a significant increase of
      protein concentration, deoxyribonucleic acid (DNA) content, and cell number in
      the cells. These increases were markedly enhanced by the presence of zinc sulfate
      (10(-5) M), but not zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(
      5) M). Also, the cellular alkaline phosphatase activity was synergistically
      increased by the presence of both IGF-I and zinc sulfate. Thus, effect was not
      seen in the presence of both insulin (10(-8) M) and zinc sulfate (10(-5) M). The
      effect of zinc sulfate to enhance the IGF-I-increased alkaline phosphatase
      activity and protein concentration in the cells was clearly prevented by the
      presence of cycloheximide (10(-6) M), staurosporin (10(-8) M), or okadaic acid
      (10(-7) M) with an effective concentration. However, staurosporin had a partial
      inhibiting effect on the IGF-I or the IGF-I plus zinc-induced increases in
      cellular protein, although okadaic acid entirely blocked the IGF-I or the IGF-I
      plus zinc effect. The present study demonstrates that the anabolic effect of IGF
      I in osteoblastic cells is enhanced by zinc ion. The enhancement by zinc may be
      mediated through the signaling pathway of protein kinase C and protein
      phosphatase in the cells.

PMID- 8532591
TI  - Angiotensin and bradykinin metabolism by peptidases identified in skeletal
      muscle.
AB  - We have identified angiotensin-converting enzyme, neutral endopeptidase-24.11,
      and aminopeptidase M in a purified glycoprotein fraction of rabbit skeletal
      muscle membranes. The identification was based on substrate specificity and
      sensitivity to selective inhibitors. Angiotensin I metabolism was due to
      angiotensin-converting enzyme-mediated conversion to angiotensin II and neutral
      endopeptidase-24.11-mediated conversion to angiotensin(1-7). Bradykinin was
      degraded by angiotensin-converting enzyme and neutral endopeptidase-24.11;
      angiotensin II by neutral endopeptidase-24.11; and angiotensin III by neutral
      endopeptidase-24.11 and aminopeptidase M. Thus, the effects of angiotensins and
      kinins on skeletal muscle blood flow and metabolism may be regulated by local
      angiotensin-converting enzyme, neutral endopeptidase-24.11, and aminopeptidase M.

PMID- 8532592
TI  - Dose and time dependency of angiotensin II inhibition of hippocampal long-term
      potentiation.
AB  - We previously reported that injection of 1.0 microliter of 4.78 microM
      angiotensin II (AII) above the hippocampus in rats inhibits long-term
      potentiation (LTP) induction in medial perforant path-stimulated dentate granule
      cells. The present experiments were conducted in urethane-anesthetized Sprague
      Dawley rats. LTP was measured in terms of the relative change in slope of the
      population EPSP compared to baseline. Effects of 0.48, 0.956, 1.195, 2.39, and
      4.78 microM AII and time delays of 30, 60, 90, and 150 min with the 4.78 microM
      dose were determined. Results were significant and demonstrate that AII
      inhibition of LTP in dentate granule cells is both dose and time dependent. The
      threshold is approximately 1.0 pmol of peptide. Inhibition due to the 4.78 microM
      AII begins slowly after 1 h and is complete over the next 30 min, continues for
      another 30 min, and then fully recovers by the end of the next 30 min. This time
      dependency could be due to the internalization of the AII, interaction with a
      cytosolic receptor, and eventual degradation.

PMID- 8532593
TI  - Opioid peptide receptor studies. 3. Interaction of opioid peptides and other
      drugs with four subtypes of the kappa 2 receptor in guinea pig brain.
AB  - Using guinea pig, rat, and human brain membranes depleted of mu and delta
      receptors by pretreatment with the site-directed acylating agents BIT (mu
      selective) and FIT (delta selective), previous studies from our laboratory
      resolved two subtypes of the kappa 2 binding site, termed kappa 2a and kappa 2b.
      In more recent studies, we used 6 beta-[125Iodo]-3,14-dihydroxy-17
      cyclopropylmethyl-4,5 alpha-epoxymorphinan ([125I]IOXY) to characterize multiple
      kappa 2 binding sites in rat brain. The results indicated that [125I]IOXY, like
      [3H]bremazocine, selectively labels kappa 2 binding sites in rat brain membranes
      pretreated with BIT and FIT. In the rat brain, using 100 nM [D-Ala2-MePhe4,Gly
      ol5]enkephalin to block [125I]IOXY binding to the kappa 2b site, we resolved two
      subtypes of the kappa 2a binding site. In the present study we examined the
      binding of [125I]IOXY to the kappa 2 receptors of guinea pig brain. As observed
      in rat brain, [125I]IOXY, under appropriate assay conditions, selectively labels
      kappa 2 binding sites. Quantitative binding studies readily demonstrated the
      presence of kappa 2a and kappa 2b binding sites. The kappa 2a binding sites were
      selectively assayed using 5 microM [Leu5]enkephalin to block [125I]IOXY binding
      to the kappa 2b sites, and kappa 2b sites were selectively assayed using 5 microM
      (-)-(1S,2S)-U50,488 to block [125I]IOXY binding to the kappa 2a sites. Under
      these conditions, two subtypes of the kappa 2a site were resolved with high
      (kappa 2a-1) and low (kappa 2a-2) affinity for nor-BNI (Ki values = 0.88 and 476
      nM) and CI977 (Ki values = 17.5 and 95,098 nM). Similarly, two subtypes of the
      kappa 2b site were observed with high (kappa 2b-1) and low (kappa 2b-2) affinity
      for [D-Ala2-MePhe4,Gly-ol5]enkephalin (DAMGO) (Ki values = 97 and 12,321 nM) and
      alpha-neoendorphin (Ki values = 33 and 5308 nM). Two-site models were also
      resolved in the presence of 100 microM 5'-guanylyimidodiphosphate (GppNHp). We
      carried out detailed ligand selectivity analysis of the multiple kappa 2 binding
      sites. Most test agents were either nonselective or selective for the kappa 2a-1
      site. Nalbuphine was moderately selective for the kappa 2a-2 site. Similarly,
      although most test agents were either nonselective or selective for the kappa 2b
      1 site, butorphanol, and the delta antagonists naltrindole, naltriben, and 7
      benzylidene-7-dehydronaltrexone were moderately selective for the kappa 2b-2
      site.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8532594
TI  - Opioid and tachykinin neuropeptides in prolactin-secreting human pituitary
      adenomas.
AB  - Two opioid neuropeptides, methionine enkephalin (ME) and beta-endorphin (BE), and
      one tachykinin neuropeptide, substance P (SP), were quantified in 10 prolactin
      (PRL)-secreting human pituitary adenomas and in 10 control human pituitaries.
      Immunohistochemical techniques provided appropriate staining for PRL. Reversed
      phase high performance liquid chromatography (RP-HPLC) was used to purify these
      three neuropeptides before their analysis, radioimmunoassay (RIA) was used for
      the quantification of SP-like immunoreactivity (SP-LI), and liquid secondary-ion
      mass spectrometry (LSIMS) was used for the qualitative and quantitative analysis
      of ME and a tryptic peptide of BE. This study shows that, for 90% of the cases
      studied here (excluding one hypothyroidism case), the tachykinin A neuropeptide
      SP-LI level is decreased, the POMC peptide BE level is not altered, and the
      proenkephalin A neuropeptide ME level is increased in these PRL-secreting tumors.

PMID- 8532595
TI  - Inhibitory cyclic analogues and chlorambucil derivatives of bombesin-like
      peptides.
AB  - Analogues of the amphibian neuropeptide, bombesin, and of the mammalian
      homologue, gastrin-releasing peptide, have been synthesized and their biological
      activity studied in small cell lung carcinoma and rat pancreatic acinar cells.
      The compounds are truncated sequences of the active tetradecapeptide BN(1-14) or
      GRP(20-27). Peptides were cyclized between position 5 or 7 and the carboxyl end
      of the des-Met14 fragment with D and L Ala11 and Lys5 substitutions, as well as
      various N-terminal groups attached. The smallest cyclic peptide, BN(7-13), bound
      to SCLC membranes with microM potency and inhibited BN stimulation of
      intracellular Ca++ levels. The most potent inhibitor is N-chloroambucil-[His7,D
      Ala11]BN(7-13)ethyl ester, which antagonized BN function in SCLC and acinar cells
      with nM potency and also inhibited clonal growth of carcinoma cell lines.

PMID- 8532596
TI  - NPY mRNA and peptide immunoreactivity in the arcuate nucleus are increased by
      osmotic stimuli: correlation with dehydration anorexia.
AB  - The role of neuropeptide Y (NPY) in the central control of appetite and energy
      balance is now established, but its involvement in the control of drinking and
      fluid homeostasis is less well characterized. Central administration of NPY
      stimulates drinking in rats, an effect believed to be independent of its
      orexigenic effects. Recent studies have demonstrated increased preproneuropeptide
      Y (preproNPY) mRNA in the arcuate nucleus (ARC) of the rat following food
      deprivation (FD) or water deprivation (WD). Because WD also suppresses food
      intake, it was not clear whether the osmotic or the anorectic effects of this
      stimulus were responsible for increased ARC preproNPY mRNA. In an attempt to
      distinguish between these possibilities, the present study further examined the
      effects of hyperosmotic stimuli on preproNPY mRNA in the ARC. Salt loading (4 or
      7 days) and WD (4 days) both increased the abundance of preproNPY mRNA in the
      ARC. These increases were proportional to the severity and duration of treatment
      and were related to the degree of anorexia and weight loss. In a separate study
      WD, FD, or combined food and water deprivation (4 days) all produced similar
      decreases in body weight, but WD produced a smaller increase in ARC preproNPY
      mRNA. All of these treatments resulted in the appearance of NPY-like
      immunoreactivity in ARC neuronal perikarya. Together these findings suggest that
      NPY neuron activity in the ARC may be regulated by decreases in food intake
      rather than changes in body weight per se or increased osmolarity and support
      other data implicating NPY in the central regulation of energy homeostasis.

PMID- 8532597
TI  - Suppression of cerebral vasodilation with endothelin-1.
AB  - We investigated the effect of endothelin-1 on relaxation responses induced by
      vasodilator substances in canine middle cerebral arteries to better understand
      regulation of cerebrovascular tone and its potential impact on mechanism of
      cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in
      helical strips of canine cerebral arteries (EC50; 4.62 x 10(-9) M). Pretreatment
      with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation
      elicited by substance P and endothelium-independent relaxations by nitroglycerin,
      prostaglandin I2, and KCl. Although endothelin-1 in a lower concentration (10(
      10) M) did not affect these endothelium-independent relaxations, it did inhibit
      endothelium-dependent relaxation caused by substance P. A low concentration (10(
      10) M) of endothelin-1 also significantly reduced endothelium-dependent
      relaxation of canine mesenteric arteries induced by acetylcholine. Other
      vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit
      endothelium-dependent and -independent relaxations. These results indicate that
      endothelin-1 not only produces cerebral vasoconstriction but also interferes with
      vasodilator mechanisms and that endothelium-dependent vasodilation is more
      sensitive to the inhibitory effect of endothelin-1 than endothelium-independent
      vasodiltion.

PMID- 8532598
TI  - Neuromedin B stimulates arachidonic acid release, c-fos gene expression, and the
      growth of C6 glioma cells.
AB  - The effects of neuromedin B (NMB) on C6 glioma cells were investigated. NMB bound
      with high affinity (IC50 = 1 nM) to C6 cells whereas BN and GRP were less potent
      (IC50 = 40 and 100 nM). NMB (1 nM) elevated cytosolic Ca2+ in individual C6 cells
      and the increase in cytosolic Ca2+ was reversed by 1 microM [D-Arg1, D-Pro2,D
      Trp7.9,Leu11]substance P [APTTL]SP, a broad spectrum antagonist. NMB stimulated
      [3H]arachidonic acid release from C6 cells and the increase in [3H]arachidonic
      acid release was reversed [APTTL]SP. NMB increased transiently c-fos gene
      expression in C6 cells. NMB increased the number of C6 colonies in soft agar and
      the increase in growth caused by NMB was reversed by [APTTL]SP. These data
      suggest that NMB receptors may regulate the proliferation of C6 cells.

PMID- 8532599
TI  - Metabolism of vasopressin, oxytocin, and their analogues in the human
      gastrointestinal tract.
AB  - The bioavailability from the gastrointestinal tract of peptides as large as
      nonapeptides is very low, which may be attributed to extensive lumenal and
      mucosal degradation. The aim of the present study was to investigate the
      stability of the neurohypophyseal hormones arginine-vasopressin (AVP), oxytocin
      (OT), and their synthetic analogues in human intestinal contents, small
      intestinal brush-border membranes, and gastric, rectal, and colonic plasma
      membranes. Peptides were incubated in gastrointestinal contents from healthy
      volunteers and in human intestinal mucosa homogenates. The extent of degradation
      was determined by reversed-phase high performance liquid chromatography (HPLC).
      AVP was rapidly degraded in the ileum fractions of the intestinal contents
      whereas 50% of the analogue 1-deamino-8-D-arginine vasopressin (dDAVP) remained
      intact after 35 min. The degradation was pH dependent, and a concentration
      dependent inhibition was observed when aprotinin, a proteinase inhibitor, was
      preincubated with contents from the ileum. No degradation of AVP, dDAVP, or
      oxytocin analogues was observed in the mucosa homogenate from the stomach. The
      peptides were found to be rather slowly degraded by intestinal microvilli
      membranes and colonic and rectal plasma membranes. This degradation occurred
      essentially when reduced glutathione 10(-4) M was added to the incubations. In
      conclusion, the major enzymatic barrier to intestinal absorption of OT, VP, and
      their analogues is present in the intestinal juice and not in the mucosa, which,
      however, constitutes a major physical barrier to peptide transport.

PMID- 8532600
TI  - Characterization of GIP(1-30) and GIP(1-42) as stimulators of proinsulin gene
      transcription.
AB  - Originally characterized in terms of its gastric acid inhibitory properties, GIP
      (gastric inhibitory polypeptide) expressed in the upper small intestine, was
      subsequently shown to exert strong glucose-dependent insulin-releasing
      properties. This action is generally attributed to GIP(1-42) and, so far, no
      evidence for the contribution of other relevant GIP forms exists. In this study,
      we compared the effects of GIP(1-42) and C-terminally truncated GIP(1-30) on cAMP
      production and proinsulin gene transcription at clonal insulin-secreting cell
      lines (RIN 1046-38, beta TC-3). Both peptides were equally potent stimulators of
      cAMP generation in both cell lines. Insulin release from RIN 1046-38 cells
      stimulated by both GIP forms was identical. In both B-cell lines GIP(1-42) and
      GIP(1-30) stimulated proinsulin gene expression equipotently. GIP not only
      enhances insulin secretion but also insulin gene expression and, therefore, it is
      a true insulinotropic hormone.

PMID- 8532601
TI  - Delta sleep-inducing peptide in normal humans and in patients with sleep apnea
      and narcolepsy.
AB  - We measured morning plasma concentrations of delta sleep-inducing-peptide-like
      immunoreactivity (DSIP-LI) in 9 sleep apnea patients, 10 narcolepsy patients, and
      11 normal controls. Comparisons between the three groups showed no significant
      differences, although there was a trend toward association with low levels of
      DSIP-LI in the narcoleptic group, particularly in patients not using medications.
      No differences were found in the morning or evening plasma DSIP-LI levels in a
      second group of 11 normal controls and 8 sleep apneics. Our findings do not
      appear to support a biological marker role of disease activity for single
      measures of plasma DSIP in sleep apnea.

PMID- 8532602
TI  - Permeability of the blood-brain barrier to melanocortins.
AB  - Adrenocorticotropin (ACTH)-related compounds, termed melanocortins, produce a
      large number of effects on the central nervous system (CNS) after their
      peripheral administration. Some of the CNS effects of ACTH are mediated through
      the release of glucocorticoids from the adrenal gland, but there are fragments
      and analogues of ACTH that do not act on the adrenals. This raises the
      possibility that some blood-borne melanocortins may be acting directly on the
      brain, which would necessitate their crossing the blood-brain barrier (BBB). We
      review here the literature showing that melanocortins can affect the BBB in
      several ways, including an alteration of the permeability of the BBB to other
      substances.

PMID- 8532603
TI  - Glucagon receptor mRNA distribution in rat tissues.
AB  - In addition to glucagon's role in regulating glucose production from the liver, a
      number of extrahepatic effects of glucagon have been reported. We have therefore
      examined various rat tissues for glucagon receptor mRNA expression. In liver,
      kidney, heart, adipose tissue, spleen, pancreatic islets, ovary, and thymus,
      glucagon receptor mRNA expression was found to be relatively abundant whereas
      lower levels were detected in stomach, small intestine, adrenal gland, thyroid,
      and skeletal muscle. The presence of glucagon receptor mRNA in tissues known to
      be responsive to glucagon suggests that these effects are mediated by specific
      glucagon receptors. Furthermore, the finding of glucagon receptor mRNA in the
      spleen, thymus, thyroid, adrenal gland, ovary, and skeletal muscle, where
      glucagon is not generally considered to act, indicates that there may be novel
      actions of glucagon that have yet to be determined.

PMID- 8532604
TI  - A novel gut tetradecapeptide isolated from the earthworm, Eisenia foetida.
AB  - A novel bioactive tetradecapeptide, GFKDGAADRISHGFamide, was isolated from the
      gut of the oligochaete annelid, Eisenia foetida, using the isolated anterior gut
      (crop-gizzard) as a bioassay system. A highly homologous peptide,
      GFRDGSADRISHGFamide, was also purified from the whole body of another species of
      earthworm, Pheretima vittata. These peptides were termed Eisenia tetradecapeptide
      (ETP) and Pheretima tetradecapeptide (PTP), respectively. Both the peptides
      showed a potent excitatory action on spontaneous contractions of the anterior gut
      with a threshold as low as 10(-10)-10(-9) M. These peptides were significantly
      homologous to molluscan tetradecapeptides and, to a lesser extent, to arthropodan
      tridecapeptides that have been reported to date. All these peptides seem to be
      evolutionally related to each other.

PMID- 8532605
TI  - Interactions between endothelial mediators.
AB  - Prostacyclin, nitric oxide and tissue plasminogen activator constitute a
      prominent triad of endothelial mediators. Prostacyclin is responsible mainly for
      maintaining vascular thromboresistance against platelet clumps, inhibits
      proliferation of vascular smooth muscle and modulates cholesterol turnover,
      tissue plasminogen activator is a fibrinolytic agent and nitric oxide controls
      vascular tone and structure. Receptor agonists such as acetylcholine, kinins,
      endothelins or adenosine diphosphate evoke a coupled release of mediators from
      endothelial cells. Prostacyclin and nitric oxide synergize in their antiplatelet,
      fibrinolytic and cardioprotective, but not in their hypotensive actions.
      Prostacyclin, but not nitric oxide, prevents paradox thrombogenic effects of
      tissue plasminogen activator. Filogenetically, prostacyclin and tissue
      plasminogen activator are younger brothers of nitric oxide from which they take
      over and perfect regulatory properties in circulation. Further studies on
      interactions of endothelial mediators may lead to a better understanding of
      mechanisms of thrombosis, atherogenesis, diabetic angiopathies, endotoxic shock
      and arterial hypertension.

PMID- 8532606
TI  - Effects of nicardipine on lipid peroxidation in rabbits given 2% cholesterol
      diet.
AB  - Nicardipine has been shown to have an anti-atherogenic effect in rabbits given a
      2% cholesterol diet. Current evidence suggests that lipid peroxidation plays an
      important role in atherogenesis. This study examines the effect of nicardipine on
      lipid peroxidation in rabbits given a 2% cholesterol diet, 8 of these rabbits
      given nicardipine 0.5 mg/kg twice daily intramuscularly for ten weeks while the
      remaining untreated 6 were controls. After ten weeks, serum malondialdehyde in
      the control group was significantly higher compared to their baseline levels (P <
      0.05). However, there was no increase in serum malondialdehyde in the nicardipine
      group after 10 weeks. The area of Sudan IV positive intimal lesions
      (atherosclerotic plaques) were significantly decreased (P < 0.01) in the treated
      group compared to the control group. The aortic tissue content of cholesterol and
      diene conjugates were also decreased in the nicardipine group (P < 0.01). These
      findings suggest a possible link between nicardipine and lipid peroxidation in
      mediating its antiatherogenic effects.

PMID- 8532607
TI  - The effects of phenobarbital pretreatment on the metabolism and toxicity of
      paraoxon in the mouse.
AB  - The effects of induction of various forms of cytochromes P450 by chemicals like
      phenobarbital on the hepatic oxidative desulfuration and acute toxicity of the
      phosphorothioate insecticide parathion have been well-characterized. However, the
      effects of these chemicals on the metabolism and acute toxicity of the active
      metabolite paraoxon are less understood. In the present study, daily pretreatment
      of mice with phenobarbital (intraperitoneally 75 mg/kg) for up to eight days
      resulted in a transient increase in hepatic microsomal A-esterase activity, with
      a corresponding transient decrease in serum A-esterase activity (A-esterase was
      defined as hydrolysis of paraoxon which could be inhibited by EDTA). These
      alterations could be accounted for by a temporary decrease in the rate of
      secretion of A-esterase from liver. However, the same pretreatment resulted in a
      sustained protective effect against the acute toxicity of paraoxon. These data
      suggest that alterations in A-esterase activity as a result of phenobarbital
      pretreatment cannot account for the observed antagonism of the acute toxicity of
      paraoxon. Furthermore, these data demonstrate that the protective effect of
      phenobarbital pretreatment on phosphorothioate insecticides like parathion cannot
      be attributed exclusively to alterations in oxidative desulfuration of these
      compounds.

PMID- 8532608
TI  - Uptake and transport of manganese in primary and secondary olfactory neurones in
      pike.
AB  - gamma-spectrometry and autoradiography were used to examine the axoplasmic flow
      of manganese in the olfactory nerves and to study the uptake of the metal in the
      brain after application of 54Mn2+ in the olfactory chambers of pikes. The results
      show that the 54Mn2+ is taken up in the olfactory receptor cells and is
      transported at a constant rate along the primary olfactory neurones into the
      brain. The maximal velocity for the transported 54Mn2+ was 2.90 +/- 0.21 mm/hr
      (mean +/- S.E.) at 10 degrees, which was the temperature used in the experiments.
      The 54Mn2+ accumulated in the entire olfactory bulbs, although most marked in
      central and caudal parts. The metal was also seen to migrate into large areas of
      the telencephalon, apparently mainly via the secondary olfactory axons present in
      the medial olfactory tract. A transfer along fibres of the medial olfactory tract
      probably also explains the labelling which was seen in the diencephalon down to
      the hypothalamus. The results also showed that there is a pathway connecting the
      two olfactory bulbs of the pike and that this can carry the metal. Our data
      further showed a marked accumulation of 54Mn2+ in the meningeal epithelium and in
      the contents of the meningeal sacs surrounding the olfactory bulbs. It appears
      from our study that manganese has the ability to pass the synaptic junctions
      between the primary and the secondary olfactory neurones in the olfactory bulbs
      and to migrate along secondary olfactory pathways into the telencephalon and the
      diencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532609
TI  - Failure of calcium antagonistic agents to prevent hepatotoxicity induced by
      diclofenac.
AB  - Diclofenac (0.5-2 mM) dose- and time-dependently reduces the viability of
      isolated hepatocytes. This effect cannot be counteracted by the calcium channel
      blockers diltiazem (0.05-0.1 mM) and verapamil (0.05-0.5 mM), the calmodulin
      antagonist calmidazolium (0.01 mM) or Quin 2-AM (0.1 mM), an intracellular
      calcium chelating agent. On the contrary, verapamil even accentuates the toxic
      effects of diclofenac. It is concluded from these results, that diclofenac causes
      cell damage by other mechanisms than calcium overload.

PMID- 8532610
TI  - Xanthine oxidase mediates paraquat-induced toxicity on cultured endothelial cell.
AB  - The role of xanthine oxidase in paraquat toxicity was investigated using cultured
      bovine pulmonary artery endothelial cells. Exposure to paraquat 0.1 mM was done
      for 24 hr with or without tungsten pretreatment and in the presence or absence of
      xanthine oxidase inhibitors. Exposure to paraquat significantly increased O2-
      production and relative xanthine oxidase activity (xanthine oxidase activity
      divided by total xanthine dehydrogenase plus xanthine oxidase) while depressing
      cell growth. In contrast, tungsten and allopurinol inhibited the increase of
      xanthine oxidase activity and decreased O2- release. Cell injury was assessed by
      leakage of lactate dehydrogenase and by fluorescein diacetate staining; it was
      found that oxidase inhibitors (both allopurinol and tungsten) reduced paraquat
      cytotoxicity. Thus the toxicity of paraquat was at least partly due to
      intracellular O2- production mediated by xanthine oxidase and the subsequent
      formation of other free radicals.

PMID- 8532611
TI  - Effect of long-term sodium selenite supplementation on levels and distribution of
      mercury in blood, brain and kidneys of methyl mercury-exposed female mice.
AB  - Female Balb/c CA mice were supplemented for seven weeks with 0, 0.6 and 3 p.p.m.
      Se in tap water and were then exposed to a single oral dose of Me203Hg (2
      mumol/kg). Se supplementation continued for 56 days after MeHg dosage.
      Supplemented animals showed enhanced activity of glutathione peroxidase in the
      blood. Twenty-four hr after MeHg dosage, the level and distribution of Hg in
      blood, blood cells, and kidneys were not influenced by Se exposure. However, in
      the brain the Hg accumulation was increased and Hg distribution was altered by Se
      supplementation. Fifty-six days after MeHg dosage, 70% to 80% of the dose had
      been eliminated from the body, and the brain of the 3 p.p.m. group still had a
      higher Hg level than the control group. Otherwise, there was no consistent effect
      of Se supplementation on retention of Hg in the animals. It is indicated that Se
      influences tissue accumulation and intracellular distribution of Hg through
      tissue-specific mechanisms rather than through a more general effect on Hg
      sequestration and transport in the blood.

PMID- 8532612
TI  - Relation between cyclic GMP generation and cerebrovascular reactivity: modulation
      by NPY and alpha-trinositol.
AB  - It is considered that cyclic guanosine monophosphate (cGMP) plays a pivotal role
      in mediating the relaxation of vascular and nonvascular smooth muscles. cGMP
      steady state levels are regulated by guanylyl cyclase, cGMP phosphodiesterases
      and its flux from cells. The present study examines the possible relation between
      cerebrovascular vasodilator agents and generation of cGMP in guinea pig cerebral
      vessels. Acetylcholine, substance P, nitroglycerine and sodium nitroprusside
      significantly increased the generation of cGMP. The application of acetylcholine,
      substance P, nitroglycerine and sodium nitroprusside elicited concentration
      dependent relaxation of basilar artery segments. Neuropeptide Y increased the
      generation of cGMP by 2%-46% of control levels (at 10(-7)-10(-6)M of neuropeptide
      Y; *P < 0.05). In addition, neuropeptide Y (10(-6)M) induced a transient
      relaxation of the precontracted guinea pig basilar arteries with endothelium.
      This transient relaxation was blocked by nitro-L-arginine (10(-4)M). alpha
      Trinositol does not alter the formation of cGMP nor the neuropeptide Y-induced
      relaxation. In the presence of alpha-trinositol neuropeptide Y (10(-7)-10(-6)M)
      did not significantly elevate the production of cGMP as compared with controls.
      The rise in cGMP induced by acetylcholine, substance P and nitroglycerine was
      slightly increased by the addition of neuropeptide Y (3 x 10(-7) M).
      Acetylcholine and substance P induced an endothelium-dependent relaxation of the
      precontracted guinea pig basilar arteries, while sodium nitroprusside and
      nitroglycerine induced an endothelium-independent relaxation. Acetylcholine,
      substance P and nitroglycerine induced concentration-dependent relaxations of
      basilar artery, respectively. The relaxation elicited by acetylcholine or
      substance P, but not nitroglycerine, was markedly attenuated by neuropeptide Y (3
      x 10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532613
TI  - Effects of enzyme induction on the distribution of the food carcinogen 2-amino
      3,8-dimethyl-imidazo[4,5-ss]-quinoxaline (MeIQx) in Ah-receptor- responsive- and
      Ah-receptor-non-responsive mice.
AB  - The distribution of the food carcinogen 2-amino-3,8-dimethyl-imidazo[4,5
      ss]quinoxaline (MeIQx) was studied in Ah-responsive-(C57BL/6J) and Ah-non
      responsive mice (DBA/2N). The time dependent organ distribution of radioactivity
      after 14C-MeIQx (10 mg/kg) administration in C57BL/6J showed that at day 4 most
      of the radioactivity had been excreted and that the remaining radioactivity was
      found in liver, kidneys, lungs and spleen. C57BL/6J bound more radioactivity in
      the kidneys than the DBA/2N strain whereas approximately the same amount was left
      in the liver and lungs in both strains 4 days after MeIQx exposure. Liver
      microsomes of the two strains had approximately the same ability to activate
      MeIQx in the Ames Salmonella assay. beta-Naphthoflavone treatment of the animals
      greatly increased microsomal activating capacity, but only in the C57BL/6J
      strain. Isosafrole treatment of the animals only slightly increased the
      activating capacity, but particularly with microsomes from the DBA/2N strain,
      displacement of the putative inhibitory isosafrole metabolite greatly increased
      their activating capacity. In the whole animals pretreatment with beta
      naphthoflavone, which induces P450IA only in the C57BL/6J strain, did not
      significantly change the amount of retained radioactivity in any of the strains.
      Isosafrole induces only P450IA2, the major N2-hydroxylating enzyme of
      heterocyclic amines, in both strains. Such pretreatment reduced the amount
      retained in the kidney of both strains whereas it reduced the retained amount of
      radioactivity in the liver with about 60% only in the Ah-non-responsive strain
      (DBA/2N). The effect of isosafrole did not persist when MeIQx was given three
      days after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532614
TI  - Inhibition of ATP-sensitive potassium channels in cardiac myocytes by the novel
      class III antiarrhythmic agent MS-551.
AB  - The novel class III antiarrhythmic agent, MS-551, has recently been shown to
      attenuate the decrease in ventricular effective refractory period and to prevent
      the subsequent ventricular fibrillation induced by pinacidil and hypoxia in
      isolated perfused rabbit hearts (Friedrichs et al. 1994). We studied the effects
      of MS-551 on single ATP-sensitive potassium channels in isolated rabbit
      ventricular myocytes using standard patch-clamp methods. MS-551 in the range from
      1 microM to 100 microM produced a concentration-dependent reduction of the open
      probability of the ATP-sensitive potassium channel, with an apparent ED50 of 30
      microM. This reduced channel activity was due to a smaller number of channel
      openings per unit time, and the average duration of each opening of the channel
      was unaffected. This property of MS-551 is likely to be of most significance in
      ischaemic tissue, where the ATP-sensitive channels are thought to carry the
      predominant current that shortens the duration of the action potential.

PMID- 8532615
TI  - Serotonergic mechanisms involved in the exploratory behaviour of mice in a fully
      automated two-compartment black and white text box.
AB  - A fully automated version of the black and white two-compartment box for mice is
      presented. The anxiolytic-like effects of the benzodiazepines, diazepam and
      chlordiazepoxide, were confirmed, and the involvement of serotonergic mechanisms
      was studied in this animal model of anxiety. The partial 5-HT1A receptor
      agonists, buspirone and ipsapirone showed anxiolytic-like effects in a limited
      dose interval. The full agonist hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT)
      was inactive. The non-selective 5-HT1 receptor agonist, eltoprazine, induced
      marked increases of exploratory behaviour in the white compartment over a broad
      range of doses. Also pindolol a mixed 5-HT1A/1B and beta-adrenergic receptor
      antagonist showed anxiolytic-like effects, whereas another compound with a
      similar profile (-)-, penbutolol and the beta-adrenoceptor antagonist ICI
      118,551, was inactive. The 5-HT2A/2C receptor antagonist, ritanserin, showed
      anxiogenic-like, and the 5-HT3 receptor antagonists, zacopride and ondansetron,
      showed anixiolytic-like effects. An overall increase of serotonergic activity by
      means of 5-HT uptake inhibition (citalopram), 5-HT release (fenfluramine) or
      administration of a 5-HT precursor (1-5-HTP) facilitated exploratory activity in
      the white compartment. Reduction of serotonergic activity by treatment with the 5
      HT depletor p-chloro-phenylalanine methyl ester (PCPA) did not change the
      exploratory behaviour, but attenuated the response to fenfluramine significantly.

PMID- 8532616
TI  - Dose-related efficiency of mono-n-hexyl meso-2,3-dimercaptosuccinate in
      decreasing 203Hg retention in rats.

PMID- 8532617
TI  - In utero diagnosis and treatment of fetal goitrous hypothyroidism, caused by
      maternal use of propylthiouracil.
AB  - A fetal goitre is a potentially dangerous phenomenon because of mechanical
      obstruction and possible fetal thyroid function disorders. In this report we
      describe a patient with Graves' disease diagnosed in early pregnancy and treated
      with propylthiouracil, which resulted in a large fetal goitre and fetal
      hypothyroidism. The diagnostic problems are discussed and we focus on the need
      for fetal thyroid hormone serum evaluation. The only reliable way to obtain
      information about the fetal thyroid status is percutaneous fetal umbilical cord
      blood sampling, since amniotic fluid levels do not properly represent the fetal
      thyroid function. Fetal hypothyroidism can thus be diagnosed in utero and treated
      with intra-amniotic injections of thyroxine. The recommended dose and frequency
      of injections are only based on a few case reports and for that reason we
      performed a second fetal blood sampling 1 week later to evaluate our therapy.
      Weekly intra-amniotic injections of 250 micrograms of thyroxine seem to be
      sufficient to reduce a fetal goitre and give a normal thyroid hormone level.

PMID- 8532618
TI  - Maternal platelet size as a marker for fetal trisomies 18 and 13.
AB  - Maternal and fetal platelet size and glycoprotein expression were measured in 14
      pregnancies complicated by fetal aneuploidy between 20 and 24 weeks' gestation.
      Flow cytometry was used to determine platelet size and surface glycoprotein Ib
      (GPIb) and GPIIIa expression both before and after stimulation with adenosine
      diphosphate (ADP). The data were compared with results obtained from 35 normal
      paired maternal and fetal controls. In fetuses affected with trisomies 18 and 13,
      but not trisomy 21, the maternal and fetal platelet sizes were significantly
      higher than those of the normal controls. Furthermore, the increase in fetal
      platelet size was significantly associated with the increase in maternal platelet
      size. Increase in maternal platelet size may be of potential value as a marker
      for fetal trisomies 18 and 13.

PMID- 8532619
TI  - Prenatal diagnosis of trisomy 9. Six cases and a review of the literature.
AB  - Six prenatally diagnosed cases of trisomy 9 are reported and 22 previously
      reported cases are reviewed; the difficulty of genetic counselling for such cases
      and the variation in the percentage of trisomic cells in different tissues, thus
      making accurate diagnosis of trisomy 9 difficult, are emphasized. In addition to
      karyotyping results, ultrasound findings are important in achieving diagnoses.
      Finally, a course of action when prenatal trisomy 9 is detected is proposed.

PMID- 8532620
TI  - A 10-year survey, 1980-1990, of prenatally diagnosed small supernumerary marker
      chromosomes, identified by FISH analysis. Outcome and follow-up of 14 cases
      diagnosed in a series of 12,699 prenatal samples.
AB  - A cytogenetic survey and follow-up studies were made of 14 cases with
      supernumerary marker chromosomes, identified among 12,699 prenatal samples,
      investigated at our institution over a 10-year period from 1980 to 1990. FISH
      (fluorescence in situ hybridization) techniques were employed to identify the
      chromosomal origin of the marker chromosomes. Five cases were familial, all
      derived from acrocentric chromosomes, and all without apparent phenotypic effects
      in the children. Nine cases represented de novo aberrations. In two cases (one
      with a marker from chromosome 14 or 22, the other with a ring-like marker derived
      from chromosome 17), the pregnancies continued and apparently normal babies were
      delivered at term, but the child with a marker derived from chromosome 17 showed
      slight psychomotor retardation at 2 years of age. All other pregnancies with de
      novo markers were terminated. In three cases, significant abnormalities were
      found at autopsy. One of these had an isochromosome 12p and the phenotype was
      consistent with Pallister-Killian syndrome. In conclusion, marker chromosome
      identification, as well as clinical follow-up, is essential for the purpose of
      improving genetic counselling.

PMID- 8532621
TI  - Alpha-fetoprotein and acetylcholinesterase activity in first- and early second
      trimester amniotic fluid.
AB  - Normal ranges of amniotic fluid alpha-fetoprotein (AFP) and acetylcholinesterase
      activity (AChE) are described for gestational weeks 11-14 using rocket gel
      immunoelectrophoresis for AFP quantitation and a monoclonal antibody (4F19)
      enzyme antigen immunoassay for AChE activity measurement. The normal ranges were
      established by the examination of 281 amniotic fluid samples from 281 normal
      pregnancies. AFP was found to increase from a median level of 14.0 MIU/l at 11
      weeks to a maximum at 13 weeks (median = 18.0 MIU/l) (P < 0.05), thereafter
      falling (not significant). No AChE test result exceeded 4.8 nkat/l. In addition,
      AFP and AChE values for three cases of fetal malformation, identified by the
      biochemical analyses of amniotic fluid, are given. These cases included two
      fetuses with a neural tube defect and one fetus with an abdominal wall defect.
      Amniocentesis was performed at 10, 11, and 14 weeks, respectively. The AFP and
      AChE values were all high.

PMID- 8532622
TI  - The significance of early second-trimester sonographic detection of minor fetal
      renal anomalies.
AB  - A study of 6350 consecutive transvaginal ultrasound examinations was performed as
      part of a routine fetal evaluation. Twenty-one cases (0.33 per cent) of early
      second-trimester sonographic detection of minor renal abnormalities (unilateral
      renal agenesis, pelvic kidney, and double collecting system) are presented. The
      sonographic diagnosis was made at 14-18 weeks of pregnancy and confirmed, in all
      of the 21 fetuses, postnatally or by post-mortem. A high incidence of associated
      fetal anomalies (24 per cent) and parental renal abnormalities (14 per cent) was
      demonstrated. Transvaginal sonography was found to be a useful tool for
      diagnosing these renal anomalies as early as 14 weeks of pregnancy. The
      likelihood of various associated anomalies and long-term implications on renal
      function raise questions concerning the prenatal management of such patients.

PMID- 8532623
TI  - Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) using molecular
      genetic techniques.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is a frequent hereditary motor and
      sensory neuropathy of the peripheral nerves. In most cases, the disease is
      associated with a 1.5 Mb tandem duplication at 17p11.2. A 42-year-old pregnant
      women requested prenatal diagnosis because of her age and since both her husband
      and two children were severely affected with CMT1. The CMT1A duplication was
      demonstrated in the father's, the two children's, and the fetus's DNA using
      different molecular genetic methods. Although cytogenetical analysis showed a
      normal female karyotype in the fetus, the parents decided to terminate the
      pregnancy because of the genetic risk associated with the CMT1A duplication.

PMID- 8532624
TI  - The time of appearance and disappearance of fetal DNA from the maternal
      circulation.
AB  - A single copy Y-chromosome DNA sequence was amplified using the polymerase chain
      reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy
      through an in vitro fertilization (IVF) programme. The time of conception was
      known precisely and was confirmed by serial ultrasound scans. Conceptions were
      dated as the number of weeks after fertilization plus 2, to give a time
      equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y-chromosome
      specific DNA was detected in all pregnancies with a male fetus (18/30). The
      earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1
      day. Y-chromosome-specific sequences were no longer detected in any of the male
      pregnancies 8 weeks after delivery. No Y-chromosome sequences were detected in
      any of the pregnancies where only female babies were delivered. This demonstrates
      that fetal DNA appears in the maternal circulation early in the first trimester,
      that it can be identified in all pregnancies tested by 7 weeks, that it continues
      to be present throughout pregnancy, and that it has been cleared from the
      maternal circulation 2 months after parturition. Early non-invasive prenatal
      diagnosis for aneuploidies and inherited disorders will be possible in all
      pregnancies if fetal cells can be isolated free from maternal contamination (or
      identified accurately in the presence of maternal cells) without problems of
      contamination from previous pregnancies.

PMID- 8532625
TI  - Genetic basis of lethal junctional epidermolysis bullosa in an affected fetus:
      implications for prenatal diagnosis in one family.
AB  - Fetal skin biopsy at 20 weeks' gestation in a woman at risk for a child with the
      lethal skin-blistering disorder junctional epidermolysis bullosa (Herlitz)
      confirmed an affected fetus. Genomic DNA from the aborted fetus was examined for
      mutations in laminin 5, a macromolecule involved in adhesion at the dermal
      epidermal junction, and a candidate protein in this condition. Polymerase chain
      reaction (PCR) amplification of exon 10 and parts of the flanking introns of the
      gene encoding the beta 3 chain of laminin 5 (LAMB3) and subsequent analysis by
      agarose gel electrophoresis showed a more slowly migrating band in the affected
      fetus compared with the normal control. Nucleotide sequencing of the abnormal PCR
      product revealed a homozygous 77 bp duplication within the exon, resulting in a
      premature termination codon 250 bp downstream from the 3' end of the duplication.
      Maternal DNA was heterozygous for the mutant and wild-type alleles. These
      findings illustrate the genetic basis of the skin disease in this case and also
      offer the prospects of a simple, rapid, and reliable first-trimester DNA-based
      prenatal, or even preimplantation, diagnostic test for future pregnancies in this
      family.

PMID- 8532626
TI  - Prenatal ultrasound diagnosis of amelia.
AB  - Amelia is a very rare form of limb reduction defect. The incidence of isolated
      amelia with or without other limb reductions is 0.4 per 100,000 births. We report
      a cluster of three cases diagnosed prenatally. One was isolated tri-amelia and
      two were isolated tetra-amelia.

PMID- 8532627
TI  - Prenatal findings in generalized amyoplasia.
AB  - Amyoplasia is a rare, sporadic condition characterized by different degrees of
      maldevelopment of the skeletal muscles, which are replaced by fibrous and fatty
      tissue. In this report, we present a case of generalized amyoplasia presenting at
      19 weeks' gestation. The most striking finding was the absence of fetal
      movements, resulting in severe multiple congenital contractures, hydrops, and
      polyhydramnios. At autopsy, histological examination of the skeletal muscle
      showed small groups of poorly developed fibres within areas of fat. This report
      suggests that generalized amyoplasia could be a common cause of severe forms of
      multiple congenital contractures, but is probably underdiagnosed at post-mortem
      because of inadequate examination of muscles. Definitive diagnosis is important
      in determining the risks of recurrence in these cases.

PMID- 8532628
TI  - Short-rib polydactyly syndrome (SRPS) type III diagnosed during routine prenatal
      ultrasonographic screening. A case report.
AB  - The prenatal diagnosis of skeletal dysplasias is often initiated by the finding
      of a shortened extremity during a routine sonographic examination. Second
      trimester diagnosis of these anomalies allows the couple to consider the option
      of terminating a pregnancy when a lethal anomaly is detected. A 21-year-old
      Bedouin woman underwent routine ultrasonographic screening at 20 weeks'
      gestation. Severe micromelia, a narrow thorax with shortened ribs, and postaxial
      polydactyly were detected. The patient delivered a male dwarf at 20 weeks'
      gestation following prostaglandin induction of labour for a diagnosis of short
      rib polydactyly syndrome type III. The prenatal ultrasonographic diagnosis of
      short-rib polydactyly syndrome type III was made at 20 weeks' gestation, allowing
      termination of the pregnancy. A proper sonographic approach to skeletal
      dysplasias allows both early detection and differentiation between lethal and non
      lethal anomalies.

PMID- 8532629
TI  - Prenatal analysis of the insulin receptor gene in a family with leprechaunism.
AB  - We report on the prenatal diagnosis of a fetus at risk of leprechaunism. We had
      previously determined the nature of the causative mutation in the insulin
      receptor gene in this family. The mutation removes a restriction site for the
      enzyme Mbo II. Genomic DNA was extracted from a chorionic villus sample and the
      3' half of exon 2 was amplified by the polymerase chain reaction (PCR) followed
      by restriction digest. Using this method, we correctly predicted an unaffected
      child.

PMID- 8532630
TI  - Carrier detection of Duchenne muscular dystrophy through analysis of DNA from
      deciduous teeth of a dead affected child.
AB  - The sister of a child affected by Duchenne muscular dystrophy (DMD) was referred
      for genetic counselling to assess the risk of her being a carrier. Her brother
      had died 15 years previously at the age of 8. There were no other affected males
      in the family. There were no methods for DNA investigation at the time of the
      child's death and the family had never been studied for linkage with polymorphic
      probes on the chromosomal region Xp21. The only tissue from which an assessment
      of the risk could be made by DNA linkage analysis was two of the child's
      deciduous teeth that the parents had kept. DNA was extracted using a protocol
      described for the recovery of ancient DNA from museum specimens and
      archaeological finds. Multiplex amplification did not reveal deletions in 19
      exons spanning the hot-spot regions for deletions within the dystrophin gene in
      Xp21. Linkage analysis using three highly polymorphic microsatellites
      demonstrated that the sister had not received the X chromosome borne by her
      brother. These results show that DNA extracted from teeth is a reliable source
      for molecular diagnosis.

PMID- 8532631
TI  - DNA-based prenatal carrier detection for group A xeroderma pigmentosum in a
      chorionic villus sample.
AB  - DNA-based prenatal carrier detection of group A xeroderma pigmentosum (XP-A) is
      reported. Chorionic villus sampling was done at the tenth gestational week in a
      pregnant woman whose first child suffers from XP-A. Genomic DNAs from the villi,
      proband, and parents were PCR (polymerase chain reaction)-amplified using three
      sets of primers, because the PCR and a subsequent enzyme digestion with HphI,
      AlwNI, or MseI may detect the three most frequent mutations of the XP-A
      complementing gene (XPAC) in Japanese XP-A patients. The results showed that the
      proband is a homozygote and that the parents and fetus are heterozygotes for a
      base substitution at the 3' acceptor site of intron 3 of XPAC, indicating that
      the fetus is a healthy carrier of XP-A. This is the first case of prenatal
      carrier detection of the disorder.

PMID- 8532632
TI  - Down's syndrome screening using urine beta-core fragment test: choice of
      immunoassay.

PMID- 8532633
TI  - Two-analyte assay for Down syndrome screening.

PMID- 8532634
TI  - Twin-twin transfusion syndrome--possible roles for Doppler ultrasound and
      amniocentesis.

PMID- 8532635
TI  - Current awareness in prenatal diagnosis.

PMID- 8532636
TI  - Purification and characterization of rat parotid glycosylated, basic and acidic
      proline-rich proteins.
AB  - A unique family of proline-rich proteins (PRPs) is induced in rats following
      prolonged isoproterenol treatment. PRPs can be divided into glycosylated (GPRP),
      basic (BPRP) and acidic (APRP) proline-rich proteins based on their
      physicochemical characteristics. Inducible rat parotid PRPs were isolated from
      aqueous extracts of parotid glands of isoproterenol-treated animals by sequential
      chromatography on columns of DEAE-Sepharose CL-6B, Sephadex G-100 and FPLC on
      Suprose-12 column. The GPRP showed a single homogeneous band on sodium
      dodecylpolyacrylamide gel electrophoresis with an estimated molecular weight of
      approximately 220,000. Compositional analysis of GPRP revealed that this protein
      contained 19.7% glutamic acid/glutamine, 28.2% proline and 9.5% glycine, and 44%
      carbohydrate, consisting of fucose (2.81g/100g), mannose (9.78g/100g), galactose
      (9.29g/100g), N-acetylglucosamine (18.03g/100g) and N-acetylgalactosamine
      (3.90g/100g). Basic PRPs consisted of a family of proteins with estimated
      molecular masses ranging from 14-45 kDa. These proteins contained 42.6% proline,
      20.65% glutamic acid/glutamine and 21.33% glycine. Acidic PRPs also comprised of
      a family of metachromatically stained ladder of 40-60 kDa containing 29.1%
      proline, 21.5% glutamic acid/glutamine and 17.8% glycine. APRP were heavily
      glycosylated containing N-acetylglucosamine (6.34g/100g), N-acetylgalactosamine
      (19.04g/100g) and glucuronic acid (38.08g/100g).

PMID- 8532637
TI  - Comparative study of four proteases from spent culture media of Porphyromonas
      gingivalis (FAY-19M-1).
AB  - Four gelatin cleaving proteases were partially purified from culture media of
      Porphyromonas gingivalis (FAY-19M-1) by sequential chromatography on columns of
      DEAE-Sepharose, Sephadex G-100 and chromatofocusing on PBE-94. The molecular mass
      of each of these proteases, estimated by relative mobility on gelatin-containing
      SDS-PAGE, was 50 kDa (Pool D1b), 120 kDa (Pool E1a), approximately 160 kDa (Pool
      E1b) and > 300 kDa (Pool A1a), respectively. These proteases also differed with
      respect to charge characteristics, inhibition profile and cleavage specificity.
      Protease pools A1a and E1a were inhibited by thiol modifying reagents. Protease
      pool A1a was also inhibited by N-tosyl-L-lysine chloromethyl ketone, and E1a was
      inhibited by antipain. Protease pool D1b was inhibited by E-64, leupeptin and
      antipain, and protease E1b was not inhibited by either of these inhibitors. The
      detailed substrate specificity of these proteases was checked by using
      chromogenic substrates, synthetic peptides and native proteins. Protease E1b was
      very active in degrading collagen, fibrinogen, fibronectin, IgG, IgA, third
      component of complement (C3), serum albumin, transferrin and varies; is directly
      proportional to 1-acid glycoprotein as substrates. Fibrinogen, fibronectin and
      complement C3 component were also cleaved by A1a, D1b and E1a. Synthetic peptides
      insulin B chain, cecropin P-1 and magainin were cleaved by E1b. Based on FAB
      analysis E1b showed preferential cleavage at hydrophobic or neutral residues.
      Protease A1a was active towards chromogenic substrates with either lys or arg in
      P1 position. Protease D1b cleaved chromogenic substrates with arg in P1 position
      and cleaved synthetic peptides magainin and (KIAGKIA)3-NH2 at lys residues also.
      Protease E1a showed glycyl-prolyl peptidase activity.

PMID- 8532638
TI  - Benzoquinones of the beetles, Tribolium castaneum and Tribolium confusum.
AB  - Tribolium castaneum and T. confusum were washed in HPLC-grade methanol, and the
      methanolic washes were analyzed by UV spectroscopy, reversed phase HPLC, and
      GC/MS. The methanolic washes from both species contained methyl-1,4-benzoquinone
      (MBQ) and ethyl-1,4-benzoquinone (EBQ). The amounts of MBQ recovered from the two
      species were not significantly different, but the amounts of EBQ and total
      benzoquinones (MBQ+EBQ) recovered from T. castaneum were significantly greater
      than for those recovered from T. confusum. The methods described are superior to
      previous methods for isolating, identifying, and quantifying the benzoquinones in
      these beetles, since they are relatively simple, fast, do not require handling of
      the beetles, and are sensitive enough to quantify the benzoquinones of a single
      beetle.

PMID- 8532639
TI  - Interference of nucleases in cyanobacterium ferredoxin purification.
AB  - Isolation of cyanobacterial ferredoxin is normally carried out using nucleases in
      order to degrade the nucleic acids that accompany this protein during the
      purification procedure. However, this practice presents the inconvenience that
      these proteins remain in trace amounts in the purified ferredoxin preparations,
      although they are not visible by electrophoretical techniques. Evidence of that
      fact is shown in this report and an alternative procedure is described for the
      rapid preparation of ferredoxin from crude extracts of Anabaena PCC 7119. The
      method involves a treatment of the crude extract with streptomycin sulphate, a
      high molecular weight polication that precipitates the nucleic acids in the
      beginning of the purification.

PMID- 8532640
TI  - Electroporation-mediated delivery of nucleolar targeting sequences from Semliki
      Forest virus nucleocapsid protein.
AB  - Electroporation was used as a powerful and simple method to probe to the
      intracellular distribution and trafficking of signal sequences. By coupling
      synthetic peptides to carrier reporter groups, specific amino acid sequences
      responsible for nucleolar targeting of Semliki Forest virus (SFV) Core (C)
      protein were found out. In the N-terminal part of the C protein the sequences
      66KPKKKKTTKPKPKTQPKK83 and 92KKKDKQADKKKKP105 are able to situate BSA or KLH as
      reporter proteins in the nucleolus, suggesting that SFV C protein contains at
      least two independent nucleolar targeting sequences.

PMID- 8532641
TI  - [Interstitial lung involvement in collagen diseases with special reference to
      bronchoalveolar lavage and lung biopsy].

PMID- 8532642
TI  - [Simultaneous measurement of arterial and end-expiratory carbon dioxide before,
      during and after voluntary hyperventilation].
AB  - Hyperventilation syndrome is considered an established diagnosis if it is
      confirmed that the patient's complaints correlate with arterial hypocapnia. In
      the diagnostic criteria set up by a group in Nijmegen, paCO2 is determined
      indirectly by measuring the end tidal CO2. Values below 4 kPa measured at rest
      and 10 or more minutes after deliberate hyperventilation are classified positive
      diagnostic criteria for hyperventilation syndrome. However, it has not been
      proven that end tidal pCO2 agrees well with paCO2 during the entire manoeuvre. We
      performed simultaneous measurements of both parameters in 10 healthy non-smokers,
      before, during and after 3 minutes of deliberate hyperventilation. A comparison
      of the values employed for diagnosing a hyperventilation syndrome (during normal
      respiration before and 10 and more minutes after hyperventilation) yields a mean
      difference of 0.39 kPa according to the statistical computation described by
      Bland and Altman (limits of the range of agreement between 0.98 and -0.18). The
      end tidal CO2 values measured during the normal respiratory phase as well as 10
      and more minutes after hyperventilation, agree well with the arterial values (the
      arterial values being slightly higher). During and shortly after hyperventilation
      the values obtained by both methods differ from one another, so that the exact
      degree of hypocapnia during a hyperventilation period cannot be assessed by
      measuring the end tidal CO2.

PMID- 8532643
TI  - [Validation of the Sleep-Doc-Porti system for ambulatory sleep apnea diagnosis].
AB  - The aim of our study was to validate the Sleep-Doc-Porti-System (SDPS), a simple
      device to monitor patients suspected of suffering from obstructive sleep apnea
      syndrome (OSAS). This digital recording system measures nasal flow, oxygen
      saturation, heart rate, and body position. To assess the reliability of results
      obtained by the SDPS, cardiorespiratory polygraphy and SDPS were performed
      simultaneously on 48 patients with OSAS (apnea/hypopnea index (AHI) 26 +/- 25)
      and 10 habitual snorers (AHI = 0.6 +/- 0.7). There was a strong correlation
      between the apnea index (AI) recorded by the SDPS and the AI (r = 98; p < 0.001)
      and AHI (r = 97; p < 0.001) obtained by polygraphy. However, the SDPS
      significantly underestimated the respiratory disturbance index, because hypopneas
      were not detected by the recorder (AI by SDPS vs. AHI by polygraphy: 19.6 +/-
      24.4 vs. 26.7 +/- 25.3; p < 0.01). With the cardiorespiratory polygraphy as
      standard, the sensitivity of the SDPS in detecting OSAS ranged between 71 and
      72%, and the specificity between 91 and 100%, depending on the AHI values of 5,
      10, 15 and 20 chosen to define severity of the disease. Reproducibility was
      assessed in 23 patients who underwent in-home monitoring in two consecutive
      nights and yielded no evidence of a "first night effect" (AI: 30.9 +/- 24.3 vs.
      33.4 +/- 23.3; p = n.s.). In 18 OSAS patients in-home monitoring was able to
      demonstrate the worsening effect of alcohol on the disease by a significant
      increase in the AI comparing the night with and without alcohol (AI: 23.1 +/-
      11.9 vs. 35.2 +/- 14.8; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532644
TI  - [Detection of Mycobacterium tuberculosis complex with polymerase chain reaction
      (PCR)].
AB  - 248 respiratory specimens were examined using by Nested-PCR and by conventional
      methods (solid and liquid media). 54 specimens were culture-positive for M.
      tuberculosis, 51 of these were detected by PCR and conventional methods, whereas
      3 were missed by PCR and 15 were only positive by PCR. 12 of the 15 culture
      negative specimens derived from patients under treatment for tuberculosis. The 3
      specimens, which are PCR negative could also be detected after modification of
      the method. The very high sensitivity depends on the high positive rate (21.8%)
      of the investigated specimens, so it is necessary to look also for other than
      pulmonary specimens, but it seems that his Nested-PCR is a highly specific and
      sensitive method for detecting of M. tuberculosis.

PMID- 8532645
TI  - [Pleuro-mediastinitis in pulmonary actinomycosis as a rare differential bronchial
      carcinoma diagnosis].
AB  - A 48-year old patient complaining of immitigable coughing with purulent and
      sanguineous sputum and a loss of weight of 8 kg within the last three months was
      admitted to our hospital. Due to anamnesis and radiological findings (tumor of
      the right side upper lung field with infiltration of the chest wall and the
      mediastinum) we suspected a bronchogenic carcinoma. As bronchoscopy and
      histological examinations of biopsies revealed no hints to the underlying
      disease, we submitted the patient to a right side explorative thoracotomy. It
      showed a tumorous involvement of the right side upper lung field with
      infiltration and partial destruction of the chest wall and infiltration of the
      apical segment of the lower lobe of the lung and a phlegmonous infiltration of
      the paratracheal tissue. Histological examination confirmed chronical course of
      actinomycosis. Therapy consisted in resection of the affected tissue and long
      term administration of antibiotics. Response to therapy was excellent concerning
      both radiological findings and subjective complaints.

PMID- 8532646
TI  - [Spontaneous regression of a small cell bronchial carcinoma].
AB  - A circular focus of 1 cm diameter was discovered by chance on a thoracic x-ray of
      a female patient of 66 years of age suffering from chronic interstitial nephritis
      due to analgesics. Bronchoscopic suction revealed histologically a small-cell
      carcinoma of the lung but there was no indication of formation of metastases. The
      patient refused any tumor-specific treatment. In the further course of the
      disease the focus showed up radiologically for seven months and was then no
      longer visible throughout the following 14 months. The patient finally died
      subsequent to an extensive posterior myocardial infarction. Postmortem
      examination excluded the presence of a primary tumor of the lung or metastases.
      Our case suggests the rare occurrence of a spontaneous regression of a small-cell
      bronchial carcinoma. Although spontaneous regression of malignant diseases is
      ascribed to immunological factors, such regression can also occur if the
      immunological system is impaired, as had been the case in this particular patient
      with chronic renal insufficiency.

PMID- 8532647
TI  - Toward understanding pancreatic disease: from architecture to cell signaling.
AB  - Each year the American Pancreatic Association sponsors the Frank Brooks Memorial
      State of the Art Lecture. The following Frank Brooks Memorial Lecture was
      delivered at the combined meeting of the American Pancreatic Association and the
      International Association of Pancreatology, which was held in Chicago, Illinois,
      November 2-4, 1994. The presentation emphasizes the necessity for understanding
      the normal architecture of the pancreas, and the nature of the changes that
      occur, as important steps in understanding the origins and progression of
      pancreatic disease. A central theme is the plasticity of the cells that comprise
      the pancreas. Encouraging new insights are being derived from studies that
      determine the signaling molecules that regulate proliferation and
      differentiation, including those studies using transgenes.

PMID- 8532648
TI  - Modulation of the relationship between amylase and chymotrypsinogen secretion in
      atropine- and MK329-infused rats.
AB  - We demonstrated previously in ad libitum fed and fasted rats that
      chymotrypsinogen and amylase secretions were weakly or not at all correlated (1).
      However, the mechanisms controlling these correlations remain undetermined. We
      investigated the influences of cholinergic and cholecystokinin-related systems on
      the relationship between amylase and chymotrypsinogen in rats. Animals provided
      with pancreatic, biliary, duodenal, and jugular vein cannulas were kept in
      restraint cages under controlled temperature and humidity, with a regular 12-h
      light cycle, and divided into five groups. The first group of fed rats was
      constantly infused with 200 micrograms kg-1 h-1 atropine, the second with 0.5 mg
      kg-1 h-1 MK329, and the third with both. In the group in which both drugs were
      simultaneously infused, 500 micrograms kg-1 h-1 atropine was intraperitoneally
      administered, whereas MK329 was infused by intravenous cannula. Two groups
      consisted of fasted rats, of which one was also atropinized (100 micrograms kg-1
      h-1). Three-day experiments were performed separately with fed rats, and 2-day
      experiments with fasted rats; atropine and/or MK329 infusion was constant over 48
      h, in both fed and fasted rats. Atropine alone did not alter the correlation
      between enzymes even though the total protein and amylase outputs decreased,
      whereas the chymotrypsinogen output increased; MK329, slowly but significantly,
      increased the correlation between enzymes, whereas it decreased the outputs for
      all secretory parameters. When both antagonists were simultaneously infused in
      fed rats, correlation coefficients between amylase and chymotrypsinogen rapidly
      and markedly increased. In fasted rats, atropine infusion induced a tremendous
      decrease in total protein and amylase mean outputs but a significant increase in
      chymotrypsinogen output, without any significant change in the correlation
      between both enzymes. These results indicate that the nonparallel secretion of
      amylase and chymotrypsinogen is strongly modulated by a cholecystokinin-dependent
      mechanism and that this modulatory process is potentiated by the parasympathetic
      system.

PMID- 8532649
TI  - Distal pancreatectomy for cancer: results in U.S. Department of Veterans Affairs
      hospitals, 1987-1991.
AB  - Although cancers of the pancreatic body and tail are often advanced at the time
      of diagnosis, resection of localized tumors can result in long-term survival. A
      search of the computerized records of the U.S. Department of Veterans Affairs
      (DVA) revealed 29 distal pancreatectomies performed for pancreatic cancer from
      1987 to 1991. Operative complications and survival data were available on all
      patients, and pathologic and staging information were retrieved on 21 patients,
      seven of whom had cancers other than pancreatic adenocarcinoma. Although 30-day
      mortality was high after distal pancreatectomy (21%), mean survival exceeded 1
      year for patients with localized pancreatic adenocarcinoma and for those with
      histologies other than pancreatic cancer. Surgical resection should be offered to
      patients with lesions of the pancreatic body and tail when metastases are not
      demonstrated; survival will likely be prolonged when nodal or systemic metastases
      are absent. These recent DVA results from a wide variety of surgeons, hospital
      sizes, and university affiliations may more closely reflect the national
      experience with this operation in patients with cancer than do single
      institutional reports.

PMID- 8532650
TI  - Hematogenous metastases of pancreatic ductal carcinoma.
AB  - To investigate the heterogeneity of hematogenous metastases of pancreatic ductal
      carcinoma, we investigated carcinomatous spread in 130 autopsy cases. Hepatic
      metastases occurred most frequently, in 81 cases (62%), which may be explained by
      the fact that all veins draining the pancreas flow into the portal system. We
      closely examined the 49 cases without hepatic metastases. Sixteen patients had
      pulmonary metastases without hepatic metastases, whereas seven had peculiar
      hematogenous metastases without hepatic or pulmonary metastases. Fifteen of these
      23 patients had pancreatic body carcinomas. The unusual patterns of spread might
      be due to (a) hepatofugal portosystemic shunting induced by splenic vein
      obstruction, (b) retrograde lymphatic infiltration from metastatic
      tracheobronchial lymph nodes, or (c) aggressive characteristics of the tumors
      indicated by peculiar histologic features such as pleomorphic or mucoepidermoid
      carcinoma, etc. Sixteen patients showed only lymph node metastases and 10 had no
      distant metastases. Seventeen of these 26 cases had pancreatic head carcinoma.
      Histologically, two patients had mucinous cystadenocarcinomas, and six had
      adenocarcinomas producing rich mucin. The average age of the group with no
      distant metastases was higher.

PMID- 8532651
TI  - Pancreatic polypeptide immunoreactivity in sporadic gastrinoma: relationship to
      intraabdominal location.
AB  - Sporadic gastrinoma is a pancreatic endocrine tumor whose ontogeny is unknown.
      The anatomic area where the vast majority of sporadic gastrinomas is found
      (pancreatic head region) corresponds topographically to the area traversed
      embryologically by the ventral pancreatic bud. Pancreatic polypeptide (PP), a 36
      amino acid hormone, is secreted by pancreatic endocrine cells derived almost
      exclusively from the ventral pancreatic bud and is proposed as a marker for
      ventral bud derivation. Based on these observations we postulate that sporadic
      gastrinomas, found around the head of the pancreas, are derived from ventral bud
      tissue and should display a high incidence of PP immunoreactivity. Overall, we
      found PP immunoreactivity in 7 of 14 (50%) gastrinomas. Of those tumors located
      to the right of the superior mesenteric artery (SMA) (around the head of the
      pancreas), seven of nine (78%) contained PP, whereas no gastrinoma to the left of
      the SMA (n = 5) contained PP (p = 0.021; Fisher exact test). Only one other
      pancreatic endocrine or exocrine tumor, a glucagonoma located to the left of the
      SMA, stained positively for PP. We conclude that sporadic gastrinomas found
      around the head of the pancreas (to the right of the SMA) have a high incidence
      of PP immunoreactivity. These findings are consistent with our hypothesis that
      sporadic gastrinomas are derived from the ventral pancreatic bud.

PMID- 8532652
TI  - Quantitative analysis of collagen and collagen subtypes I, III, and V in human
      pancreatic cancer, tumor-associated chronic pancreatitis, and alcoholic chronic
      pancreatitis.
AB  - The collagen content in human pancreatic cancer tissue, tissue of tumor
      associated chronic pancreatitis (TACP), and normal pancreatic tissue was
      determined in 14 patients with pancreatic cancer by measuring the amount of 4
      hydroxyproline. Four patients with alcoholic chronic pancreatitis (AlCP) were
      also analyzed. The mean collagen content in both pancreatic cancer tissue and
      TACP tissue was approximately threefold higher than in normal pancreatic tissue.
      Cyanogen bromide peptides of type I, III, and V collagens from invasive ductal
      carcinomatous tissue of the pancreas and from TACP tissue of eight patients were
      analyzed sequentially using high-performance liquid chromatography with ion
      exchange and gel-permeation columns. No difference in the proportion of type I,
      III, and V collagens was detected between pancreatic cancer tissue and TACP
      tissue. The mean collagen content in AlCP tissue was significantly lower than
      that in TACP tissue, but no difference in the proportion of type I, III, and V
      collagens was detected between these two tissues. These results indicate a
      similar quantity and distribution pattern of fibrillar collagen in human
      pancreatic cancer and TACP.

PMID- 8532653
TI  - The influence of abdominal sepsis on acute pancreatitis in rats: a study on
      mortality, permeability, arterial pressure, and intestinal blood flow.
AB  - Bacterial infection increases mortality and morbidity in acute pancreatitis. The
      aim of the present study was to analyze possible mechanisms by which bacterial
      infectious complications may worsen the course of the disease. Systemic arterial
      pressure, mucosal microcirculation, and intestinal, peritoneal, and pulmonary
      permeability of 125I-labeled human serum albumin were measured 3, 6, 12, 24, 48,
      and 72 h after sham operation, induction of pancreatitis (AP), abdominal sepsis
      (AS), or AP+AS. The mortality rate at 48 and 72 h was 33% in AS and 58 and 75%,
      respectively, in AP+AS, whereas there were no deaths in the AP or sham-operated
      groups. The systemic arterial pressure and intestinal blood flow decreased early
      in all study groups, with the lowest values for AP+AS. Bacterial infection
      aggravated the increase in intestinal, peritoneal, and pulmonary permeability to
      labeled albumin in pancreatitis. This was true for both intestinal endothelial
      permeability (blood to tissue) and mucosal barrier permeability (blood to lumen).
      The findings demonstrate the occurrence of circulatory failure and changes of the
      capillary barrier in multiple organs in acute pancreatitis. Moreover, the changes
      were aggravated by an intraabdominal septic challenge. The observations imply
      that bacterial infection may play a role in the development of multiple organ
      failure in acute pancreatitis, tentatively by aggravating alterations in tissue
      barrier function.

PMID- 8532654
TI  - Does acute pancreatitis progress to chronic pancreatitis? A microvascular
      pancreatitis model in the rat.
AB  - Ischemia as a causative factor for acute pancreatitis has been discussed for
      decades but has only recently gained wider acceptance. Chronic pancreatitis,
      however, has rarely been attributed to ischemic injury. While experimental
      evidence is available for the ischemic pathogenesis of acute pancreatitis, no
      studies have been reported about pancreatic ischemia as a single cause of chronic
      pancreatitis. Also, the progression from acute to chronic pancreatitis has been a
      very controversial issue. To address both questions we have injected polystyrene
      microspheres of 20-microns diameter into the pancreatic branches of the splenic
      artery of 36 rats. Thirteen more rats were sham operated and injected with
      saline. The animals were killed at 1, 2, 3, and 9 weeks after operation and
      macroscopically and histologically examined, and serum alpha-amylase and weight
      gain were determined. For the pancreas the following parameters were assessed
      using a score from 0 (no change) to 4 (severe change): atrophy, hemorrhage,
      edema, fat necrosis, acinar necrosis, polymorphonuclear infiltration, mononuclear
      infiltration, interstitial fibrosis, and ductal changes. While no difference
      between control and experiment was observed for serum alpha-amylase, weight gain,
      edema, and hemorrhage, persistent differences were evident for the parameters
      characteristic of chronic pancreatitis, most significantly for interstitial
      fibrosis, ductal changes, mononuclear infiltration, acinar necrosis, and atrophy.
      No spontaneous deaths occurred. The severity of the lesions remained stationary
      after the first week. Our work shows for the first time that pancreatic ischemia
      by microvascular hypoperfusion can cause histopathologic changes characteristic
      of chronic pancreatitis and that these changes follow acute necrotizing
      pancreatitis.

PMID- 8532655
TI  - Oxygen radical generation and acute pancreatitis: effects of dibutyltin
      dichloride/ethanol and ethanol on rat pancreas.
AB  - Recent studies suggest that enhanced release of free oxygen radicals plays an
      important role in the pathogenesis of acute pancreatitis. Therefore, we studied
      the activity of the oxygen radical generating xanthine oxidase (XOD) in
      pancreatic tissue from rats treated with either dibutyltin dichloride/ethanol
      (DBTC/EtOH: 6 mg kg-1/13.7 mg kg-1, i.v.), ethanol alone (EtOH: 13.7 mmol kg-1,
      i.v.), or isotonic saline (NaCl) as control. We also investigated activities of
      the oxygen radical scavengers superoxide dismutase (SOD) and glutathione
      peroxidase (GPX). In addition, levels of the lipid peroxidation marker
      malondialdehyde (MDA) were determined. Enhanced activity of XOD was not detected.
      While SOD activity 1 and 6 h after treatment was significantly more reduced by
      DBTC/EtOH than by EtOH alone, no difference was found thereafter.
      Correspondingly, both regimens diminished GPX activity. Moreover, DBTC/EtOH and
      EtOH rapidly increased MDA levels within 1 h, indicating release of oxygen
      radicals early on after administration. After 16 h the MDA concentration was
      still elevated only in the DBTC/EtOH group. Although similar metabolic
      alterations were observed in both groups, only DBTC/EtOH induced acute
      interstitial pancreatitis within 24 h. We conclude that (a) a tissue imbalance
      between oxidants and antioxidants might be of importance in the pathogenesis of
      DBTC/EtOH-induced acute interstitial pancreatitis; (b) although EtOH increases
      oxygen radical levels, additional damage is required for development of acute
      pancreatitis; (c) XOD does not seem to be responsible for significant oxygen
      radical generation; and (d) the DBTC/EtOH model is a useful tool to study acute
      interstitial pancreatitis in rats.

PMID- 8532656
TI  - Scanning electron microscopic observation of pancreatic ducts in WBN/Kob rats.
AB  - To elucidate changes of pancreatic ducts in chronic pancreatitis, we observed
      pancreatic tissues with light microscopy and scanning electron microscopy, and
      corrosion casts of pancreatic ducts with scanning electron microscopy, in male
      WBN/Kob rats, considered a spontaneously occurring chronic pancreatitis model. At
      3 months of age, hemorrhage and increased fibrosis were found in part of the
      pancreatic tail. After 3 months of age, pancreatic ductal lumina exhibited a
      winding form and inner surfaces showed long cilia and crater-like depressions.
      Fibrous tissues gradually extended into exocrine tissues and islets after 6
      months of age. Most pancreatic ductal lumina developed a helical form with many
      deep depression at 14 months of age. It is suggested that increased pancreatic
      ductal pressure causes these findings.

PMID- 8532657
TI  - Quantitative immunohistochemical changes in the endocrine pancreas of nonobese
      diabetic (NOD) mice.
AB  - The nonobese diabetic (NOD) mouse is an animal model that shares a number of
      clinical, genetic, and immunologic characteristics with human insulin-dependent
      diabetes mellitus. Since little is known about the morphometric cell profiles in
      the endocrine pancreas of these NOD animals, it was of interest to assess their
      changes in morphometry within the pancreatic islet cell types during two stages
      of this syndrome. Prediabetic (6-week-old) and diabetic (16-week-old) NOD female
      mice, as well as normal C57BL/6 female mice (15 weeks old), were used. Light
      microscopic immunocytochemical and morphometric methods were employed to study
      the endocrine cell populations. The immunoperoxidase technique for the
      identification of insulin, glucagon, somatostatin, and pancreatic polypeptide, as
      well as the point-counting method, was used on serial sections of pancreas
      tissue. Compared to those of normal and prediabetic mice, pancreata from diabetic
      animals showed a decrease in both the number of islets and the volume density of
      the endocrine component. Analysis of islet tissue revealed a significant
      diminution of B-cell volume density, as well as an increased A-, D-, and PP-cell
      volume density. A parallel variation in the number of B and non-B cells was also
      found. In addition, when the total pancreatic tissue surface was taken as
      reference, the fractional area occupied by all the different types of islet cells
      was seen to be diminished in a variable fashion. We conclude that the diabetic
      syndrome of NOD mice not only severely affects the B-cell mass, but also causes
      marked changes in the non-B endocrine-cell populations.

PMID- 8532658
TI  - Effects of diet on cholecystokinin-stimulated amylase secretion by pancreatic
      Acini and amylase mRNA levels in rat pancreas.
AB  - To investigate the mechanisms by which dietary compositions regulate the exocrine
      pancreas, we examined the effects of no-fat diet (NFD) and high-fat diet (HFD) on
      cholecystokinin (CCK)-stimulated amylase secretion from rat pancreatic acini.
      Rats were maintained for 4 weeks on NFD or HFD, which contained 0 or 45% fat and
      58 or 29% carbohydrates, respectively. Pancreatic acini were isolated and
      stimulated by graded doses of CCK for 30 min. Maximal CCK-stimulated amylase
      secretion by pancreatic acini from rats on NFD (23.1 +/- 4.3 U/mg protein at 10(
      10) M) was significantly higher than that of HFD (5.5 +/- 1.6 U/mg protein at 10(
      10) M). In contrast, expressed as a percentage of the initial content, maximal
      CCK-stimulated amylase secretion by pancreatic acini from rats on NFD (15.0 +/-
      0.8%) tended to be lower than that from rats on HFD (28.1 +/- 3.5%). To study
      further the effects of the diets on amylase mRNA levels, another group of rats
      was maintained on the respective diets for 4 weeks, sacrificed, and total
      pancreatic RNA isolated. Amylase mRNA levels in rats on NFD were 2.5 times higher
      than in rats on HFD. The results suggest that alterations in CCK-stimulated
      amylase secretion by pancreatic acini, as well as modifications in pancreatic
      amylase expression, may be involved in the mechanisms by which the exocrine
      pancreas adapts to diet.

PMID- 8532659
TI  - Effects of pancreaticobiliary duct obstruction on the exocrine and endocrine rat
      pancreas.
AB  - Experimentally, biliary obstruction can produce morphological and functional
      changes in the pancreatic gland, whereas pancreatic obstruction may have short
      term (hyperamylasemia, pancreatic edema, and lysosomal hydrolase redistribution)
      or long-term (acinar cell atrophy and interstitial fibrosis) effects. We created
      a pancreaticobiliary duct obstruction in rats to evaluate (a) exocrine and
      endocrine anatomobiochemical pancreatic modifications; (b) structural and
      functional liver alterations; and (c) the relationship, if any, between the
      alterations found in the two organs. Forty-five male Sprague-Dawley rats were
      subdivided on the basis of period of obstruction (from 1 to 28 days). In each rat
      serum we evaluated amylase, cholestatic and cytolytic indices, and glucose. In
      frozen pancreatic samples we measured insulin, glucagon, and DNA; in the liver
      the DNA content was determined. Histologically, ductal dilation and proliferation
      were evaluated for the liver, zymogen granules, and Langerhans' islets, and
      atrophy for the pancreas. Fibrosis was evaluated for both the liver and the
      pancreas. Short-term common pancreaticobiliary duct ligation caused an increase
      in serum amylase levels and mild pancreatic edema. Longer-term obstruction had
      either similar or different effects on the two organs. In the pancreas it caused
      fibrosis and exocrine and endocrine atrophy, but not acute pancreatitis. In the
      liver the main phenomena observed were fibrosis, ductal dilation, and
      proliferation.

PMID- 8532660
TI  - Mineralogy and pathogenesis of pancreatic calculi.

PMID- 8532661
TI  - In search of the ideal protein sequence.
AB  - The inverse of a folding problem is to find the ideal sequence that folds into a
      particular protein structure. This problem has been addressed using the topology
      fingerprint-based threading algorithm, capable of calculating a score (energy) of
      an arbitrary sequence-structure pair. At first, the search is conducted by
      unconstrained minimization of the energy in sequence space. It is shown that
      using energy as the only design criterion leads to spurious solutions with
      incorrect amino acid composition. The problem lies in the general features of the
      protein energy surface as a function of both structure and sequence. The proposed
      solution is to design the sequence by maximizing the difference between its
      energy in the desired structure and in other known protein structures. Depending
      on the size of the database of structures 'to avoid', sequences bearing
      significant similarity to the native sequence of the target protein are obtained
      using this procedure.

PMID- 8532662
TI  - Independence divergence-generated binary trees of amino acids.
AB  - The discovery of the relationship between amino acids is important in terms of
      the replacement ability, as used in protein engineering homology studies, and
      gaining a better understanding of the roles which various properties of the
      residues play in the creation of a unique, stable, 3-D protein structure. Amino
      acid sequences of proteins edited by evolution are anything but random. The
      measure of nonrandomness, i.e. the level of editing, can be characterized by an
      independence divergence value. This parameter is used to generate binary tree
      relationships between amino acids. The relationships of residues presented in
      this paper are based on protein building features and not on the physico-chemical
      characteristics of amino acids. This approach is not biased by the tautology
      present in all sequence similarity-based relationship studies. The roles which
      various physico-chemical characteristics play in the determination of the
      relationships between amino acids are also discussed.

PMID- 8532663
TI  - Predicting protein structural classes from amino acid composition: application of
      fuzzy clustering.
AB  - Most globular proteins can be classified into one of four structural classes--all
      alpha, all-beta, alpha + beta and alpha/beta--depending upon the type, amount and
      arrangement of secondary structures present. In this work a new method, based
      upon fuzzy clustering, is proposed for predicting the structural class of a
      protein from its amino acid composition. Here, each of the structural classes is
      described by a fuzzy cluster and each protein is characterized by its membership
      degree, a number between zero and one in each of the four clusters, with the
      constraint that the sum of the membership degrees equals unity. A given protein
      is then classified as belonging to that structural class corresponding to the
      fuzzy cluster with maximum membership degree. Calculation of membership degrees
      is carried out using the fuzzy c-means algorithm on a training set of 64
      proteins. Results obtained for the training set show that the fuzzy clustering
      approach produces results comparable with or better than those obtained by other
      methods. A test set of 27 proteins also produced comparable results to those
      obtained with the training set. The success of the present preliminary work on
      protein structure class prediction suggests that further refinements of method
      may lead to improved predictions and this is currently being investigated.

PMID- 8532664
TI  - Hydrophobic potential by pairwise surface area sum.
AB  - An approximate but rapid method for estimating hydrophobic energy is proposed.
      Aside from a scale factor, it is given by the pairwise sum of the surface area
      buried by each neighbor atom, but excluding those atoms in the same residue or in
      its sequence neighbor residues. This sum is found to be linearly related to the
      true buried area as calculated by the algorithm of Lee and Richards [1971, J.
      Mol. Biol., 55, 379-400], and to the contact potential of Miyazawa and Jernigan
      [1985, Macromolecules, 18, 534-552]. It correlates with experimental transfer
      free energies to approximately the same degree as that calculated using the true
      buried area. Furthermore, in a simple test of helix packing with ROP protein
      monomer, the new hydrophobic energy clearly discriminated one structure, with the
      lowest r.m.s. deviation from the crystal structure, against an exhaustive set of
      others.

PMID- 8532665
TI  - Molecular dynamics simulation of fungal cellulose-binding domains: differences in
      molecular rigidity but a preserved cellulose binding surface.
AB  - A total of 23 fungal cellulose-binding domain (CBD) sequences were aligned.
      Structural models of the cellulose-binding domain of an exoglucanase (CBHII) and
      of three endoglucanases (EGI, EGII and EGV) from Trichoderma reesei cellulases
      were homology modelled based on the NMR structure of the fungal cellobiohydrolase
      CBHI, from the same organism. The completed models and the known structure of the
      CBHI cellulose-binding domain were refined by molecular dynamics simulations in
      water. All four models were found to be very similar to the structure of the CBHI
      cellulose-binding domain and sequence comparison indicated that in general the
      three-dimensional structures of fungal cellulose-binding domains are very
      similar. In all the CBDs studied, two disulphide bridges apparently stabilize the
      polypeptide fold. From the models, and additional disulphide bridge was predicted
      in EGI and CBHII, and in eight further CBDs from other organisms. Three highly
      conserved aromatic residues on the hydrophilic side of the wedge make this
      surface flat. This surface is expected to make contact with the substrate. Three
      invariant amino acids, Gln7, Asn29 and Gln34, on this flat face are in suitable
      positions for hydrogen bonding with the cellulose surface. Analysis of the
      differences in the protein surface properties indicated that the endoglucanases
      tend to be more hydrophilic than the exoglucanases. The largest structural
      variation was found around positions 12-16. The fungal CBD sequences are
      discussed in relation to variations in function and pH dependence. Comparison of
      the modelled structures with experimental binding data for the CBHI and EGI
      allowed the formulation of a qualitative relationship to cellulose
      affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532666
TI  - Biosynthetic incorporation of 7-azatryptophan into the phage lambda lysozyme:
      estimation of tryptophan accessibility, effect on enzymatic activity and protein
      stability.
AB  - The phage lambda lysozyme (lambda L) contains four tryptophans. These have been
      efficiently replaced by 7-azatryptophan (7aW) through biosynthetic incorporation
      into the overexpressed protein. Comparative analysis of the effect of temperature
      or pH on the fluorescence of the wild-type lambda L and 7aWs-containing protein
      (a lambda L) shows that the stability of the protein is only mildly reduced by
      7aW incorporation above pH 5 but that it is strongly decreased below pH 4 on
      protonation of inaccessible 7aWs. The a lambda L fluorescence depends on pH as a
      consequence of its effect on the denaturation equilibrium, on the state of
      protonation of accessible 7aWs in the native state and of all 7aWs in the
      denatured state. The pH dependence of the fluorescence is used to estimate the
      number of accessible tryptophans in the protein. The result agrees with that
      derived from tryptophan NH exchange measurements by 1H-NMR. The acid limb of the
      activity-pH profile is characterized by a sharp drop that might arise from a
      cooperative acid-induced denaturation. The difference in acid stability of a
      lambda L versus lambda L is used to rule out this acid denaturation hypothesis as
      tryptophan replacement does not affect the lytic activity on chloroform
      sensitized Escherichia coli cells or its pH profile.

PMID- 8532667
TI  - Engineering yeast alcohol dehydrogenase. Replacing Trp54 by Leu broadens
      substrate specificity.
AB  - Analysis of a crystal structure of alcohol dehydrogenase (Adh) from horse liver
      suggests that Trp54 in the homologous yeast alcohol dehydrogenase prevents the
      yeast enzyme from efficiently catalysing the oxidation of long-chain primary
      alcohols with branching at the 4 position (e.g. 4-methyl-1-pentanol, cinnamyl
      alcohol). This residue has been altered to Leu by site-directed mutagenesis. The
      alteration yields an enzyme that serves as an effective catalyst for both longer
      straight-chain primary alcohols and branched chain alcohols.

PMID- 8532668
TI  - Yeast expression and phagemid display of the human urokinase plasminogen
      activator epidermal growth factor-like domain.
AB  - The human urokinase plasminogen activator (uPA) epidermal growth factor-like
      domain (residues 1-48) and a variant with a C-terminal epitope tag have been
      secreted from recombinant yeast. Purified human uPA 1-48 and uPA 1-48glu complete
      for binding to the human uPA receptor with Kds of 180 and 400 pM respectively, in
      an in vitro assay using an immobilized recombinant uPA receptor. A synthetic gene
      encoding human uPA 1-48 with an N-terminal epitope tag was inserted into a
      phagemid expression vector as a fusion with residues 249-406 of the M13 pIII
      protein with an intervening amber codon (TAG). Phagemid production led to
      infectious particles which were selectively bound and eluted from both epitope
      tag antibody and urokinase receptor. Sequential binding to this antibody and
      receptor demonstrated a substantial enrichment, where up to 10% of the infectious
      particles were then retained on urokinase receptor-coated plates. A PCR strategy
      was used to convert previously described peptide bacteriophage ligands for the
      urokinase receptor to phagemid display. The yields of these peptide phagemids and
      the uPA 1-48 phagemid showed a correlation with peptide affinity, in contrast to
      when the peptides are multivalently displayed on a bacteriophage.

PMID- 8532669
TI  - Interaction between a Fab fragment against gp41 of human immunodeficiency virus 1
      and its peptide epitope: characterization using a peptide epitope library and
      molecular modeling.
AB  - The molecular interaction of the Fab fragment of the human monoclonal antibody
      3D6, directed against the transmembrane protein gp41 of human immunodeficiency
      virus (HIV) 1, with its peptide epitope is characterized by a panel of
      overlapping peptides, a peptide epitope library and molecular modeling
      techniques. The sequence CSGKLICTTAVPW, corresponding to amino acids 605-617 of
      gp41, was identified as the best binding peptide (KD = 1 x 10(-8) mol/l). This
      peptide served as a starting point to prepare a cellulose-bound peptide epitope
      library in which each residue of the epitope is substituted by all L- and D-amino
      acids, resulting in 494 epitope peptide variants which were subsequently analyzed
      for binding 3D6. The library was synthesized to identify residues critical for
      binding and to obtain information about the molecular environment of the epitope
      peptide bound to 3D6. Both cysteine residues, as well as isoleucine 6, threonine
      8 and proline 12, of the epitope were highly sensitive to substitution. Using the
      data obtained from the epitope characterization, as well as a low-resolution
      electron density map of a 3D6 Fab-peptide complex, a 3-D model of the Fab-peptide
      complex was generated by molecular modeling. The modeling experiments predict
      binding of the peptide, which is cyclized via the two cysteine residues, to a
      pocket formed dominantly by the hypervariable loops complementarity determining
      regions CDR3L, CDR2H and CDR3H.

PMID- 8532670
TI  - Expression and secretion of a recombinant ricin immunotoxin from murine myeloma
      cells.
AB  - Expression plasmids carrying a humanized N901 immunoglobulin heavy chain gene
      (hN901HC) fused to a gene encoding the native B chain of ricin toxin (RTB),
      hN901HC-RTB, or a sugar binding mutant of RTB, hN901HC-RTB delta gly, were
      constructed. In each case, the fused gene constructions were co-expressed in
      murine myeloma cells (Sp2/0) with the gene for humanized N901 immunoglobulin
      light chain to produce the secreted recombinant products hN901-RTB and hN901-RTB
      delta gly, respectively. When purified by affinity chromatography, both the hN901
      RTB and hN901-RTB delta gly products were found to have an apparent molecular
      mass of M(r) = 210,000 and to be composed of two hN901 antibody heavy chains each
      fused to a full-length copy of RTB and two hN901 antibody light chains. In each
      of the recombinant fusions the hN901 antibody moiety retained the full binding
      affinity and specificity for its cognate antigen, CD56. Moreover, when mixtures
      of hN901-RTB and native ricin A chain were incubated in the presence of the
      antigen-positive target cell line SW-2, antigen-specific potentiation of ricin A
      chain cytotoxicity was observed. It has been demonstrated previously that lectin
      activity of the B chain is essential for A chain cytotoxicity, and we conclude
      that the fused wild-type B chain was properly folded and maintained lectin
      activity. These data demonstrate that feasibility of using recombinant ricin B
      chain in an immunotoxin and of using mammalian cell culture for its expression.
      The use of recombinant hN901-RTB fusion protein to evaluate the contribution of
      the lectin activity of ricin B chain in the penetration of cell membranes by
      ricin A chain is proposed.

PMID- 8532671
TI  - Restoration of pore-forming activity in staphylococcal alpha-hemolysin by
      targeted covalent modification.
AB  - In previous studies, the replacement of His35 in the pore-forming protein alpha
      hemolysin (alpha HL) with Leu, Ile, Pro, Arg, Ser, Thr or Cys yielded inactive
      polypeptides. Here, we show that modification of the inactive single-cysteine
      mutant alpha HL-H35C with iodoacetamide, to form H35CamC, generates significant
      pore-forming activity. The closely related polypeptides H35N and H35Q have,
      respectively, essentially no activity and greatly reduced activity. The modified
      residue in H35CamC, S-carboxamidomethyl-cysteine, mimicks histidine in volume,
      polarity and hydrogen bonding potential, but is unable to ionize. Unmodified H35C
      is defective in the final step of pore formation: the conversion of an inactive
      heptameric membrane-bound assembly intermediate to a structure containing open
      channels. It is this step in assembly that is ameliorated in H35CamC.

PMID- 8532672
TI  - In vivo system for the detection of low level activity barnase mutants.
AB  - We report the design of a new tightly controlled barnase system which allows the
      existence of the barnase gene in host cells without a signal sequence. When
      expression of barnase is turned on by gene inversion in vivo, the lethal effect
      of barnase (or its mutants) is not compromised either by coexpression of its
      polypeptide inhibitor (barstar), or by extracellular secretion. This serves as a
      rapid, sensitive in vivo test for the detection of any very low residual activity
      of the barnase mutants. Active-site mutants His102Lys, Glu73Asp and Arg87Lys, and
      a mutant which greatly reduces the stability and yield of protein, Arg83Lys,
      produce enough activity to be detectable by this test. In contrast, when
      expressed on a secretion vector, these mutants do not yield detectable activity
      in a solution assay. Truly inactive mutants, such as those of His102 to Gly, Ala
      or Leu, were completely harmless when expressed in this system.

PMID- 8532673
TI  - Representative selection of proteins based on nuclear families.
AB  - The selection of unbiased representatives from a large database is complicated by
      the requirement for the chosen entries to be not only genuinely different from
      each other but also typical for the family of related entries. A method
      satisfying this 2-fold objective was developed by equipping complete linkage
      clustering with a novel noise elimination procedure to deal with overlapping
      cluster structure. A total of 200 nuclear families of truly related Brookhaven
      Protein Data Bank structures were generated, from which any entry can be chosen
      to represent its family.

PMID- 8532674
TI  - Accurate prediction of protein secondary structural class with fuzzy structural
      vectors.
AB  - The prerequisites for accurate prediction of protein secondary structural class
      (all-alpha, all-beta, alpha+beta, alpha/beta or multidomain) were studied, and a
      new similarity-based method is presented for the prediction of the secondary
      structural class of a protein from its sequence. The new method uses
      representatives of nuclear families as a learning set. For the sequence to be
      predicted, the method produces a vector of certainty factors called a fuzzy
      structural vector. Validation with independent test sets shows that the
      prediction accuracy of the proposed method has clear dependency on the
      representativity of the learning set. The representatives obtained from the
      nuclear families of the Brookhaven Protein Data Bank (PDB) were shown to give
      accurate predictions for PDB proteins, whilst the amino acid composition-based
      methods used previously achieve their maximum predictability with relatively
      limited learning sets, and they remain inaccurate even with highly representative
      learning sets. The usability of the new method is increased further by the fuzzy
      structural vectors, which substantially reduce the risk of misclassification and
      realistically describe vague secondary structural tendencies.

PMID- 8532675
TI  - Identification and analysis of domains in proteins.
AB  - An automatic algorithm based on inter-residue contacts is presented to identify
      domains in proteins. The results of the algorithm are compared to an assignment
      performed by inspection that was guided by the authors' description in the
      literature. The authors' and the algorithm's assignments for a chain were
      considered to agree if the same number of domains were identified and if the
      assignments were the same for at least 95% of the residues. With this criterion,
      the algorithm agreed with the authors' assignment for 78% of the 284 non
      redundant chains considered. When some of the authors' assignments were re
      evaluated based on the results of the algorithm, an agreement of 84% was
      obtained. The algorithm is therefore a useful tool for data validation in domain
      assignment. The authors assignments of domains were analysed for structural
      principles of domains. The number of chains forming one, two, three, four and
      five domains are 197, 67, 13, 6 and 1 respectively. Most domains in multidomain
      proteins are formed from continuous segments and adopt the same structural class.
      Distributions of the number of residues and the ellipticity of domains and chains
      are presented. The relationship between accessible surface area and molecular
      weight for domains and chains is examined.

PMID- 8532676
TI  - Prediction and analysis of SH2 domain-phosphopeptide interactions.
AB  - Src homology 2 (SH2) domains are small protein modules of approximately 100 amino
      acids that are found in many proteins involved in intracellular signal
      transduction. They mediate protein-protein interactions and modulate enzyme
      activity by their ability to bind to specific sequence patterns that contain a
      phosphorylated tyrosine. As the three-dimensional structures of the
      phosphatidylinositol (PI) 3-kinase, Lck, Src and Abl SH2 domains have been shown
      to be similar, we have modelled other SH2 domains that show distinct sequence
      specificity to allow comparative analysis of SH2-phosphopeptide interactions. The
      SH2 domains of PLC gamma-Nterm., Nck, Grb2, GAP and Abl have been model-built
      with high-affinity phosphopeptides fitted into the putative binding sites. For
      each SH2 domain a detailed analysis of the peptide-protein interaction was
      performed. It is apparent that specificity is mainly conferred by three to five
      residues downstream from the phosphotyrosine residue (Y*), especially, although
      not exclusively, peptide position Y* + 3. The SH2 pocket that binds the Y* + 3
      residue is mainly composed of three sections: part of strand beta E going into
      loop EF, part of alpha B and loop BG. The residues that constitute the Y* + 3
      binding pocket show variability that seems to determine which amino acid binds
      preferentially. Residue position beta E4 seems to play a vital role in the SH2
      specificity. This study shows that the development of modelling protocols for SH2
      domains whose structure has not been determined can prove very useful in
      predicting which residues are involved in conferring the affinity and binding
      specificity of these domains towards distinct phosphotyrosine-containing
      sequences.

PMID- 8532677
TI  - The predicted secondary structure of the G-type glutamine amidotransferase is
      compatible with TIM-barrel topology.
AB  - Glutamine amidotransferase (GAT) subunits or domains catalyze an important
      partial reaction in many complex biosynthetic reactions. The structure of one
      member of the F-type GATs is known, but the structure of the unrelated G-type is
      still unknown. Because many protein sequences are available for anthranilate
      synthase component II (product of the trpG gene), we have predicted its average
      secondary structure by a joint prediction method [Niermann and Kirschner (1991a)
      Protein Engng, 4, 359-370]. The predicted eight beta-strands and seven alpha
      helices follow an 8-fold cyclic repetition of a beta-strand-loop-alpha-helix-loop
      module with helix alpha 7 missing. This pattern of secondary structure suggests
      that the G-type GAT domain has an 8-fold beta alpha-barrel topology, as found
      first in triose phosphate isomerase (TIM-barrel). This model is supported by the
      location of known catalytically essential residues in loops between beta-strands
      and alpha-helices. Evidence from published sequencing and mutational studies on
      selected members of the GAT superfamily (carbamoyl phosphate, imidazoleglycerol
      phosphate, GMP and CTP synthases) support both the secondary structure prediction
      and the TIM-barrel topology.

PMID- 8532678
TI  - Electrostatic analysis of DNA binding properties in lysine to leucine mutants of
      TATA-box binding proteins.
AB  - The structures of the complexes between TATA-box binding proteins (TBPs) and DNA
      solved recently with X-ray crystallography identify both direct and indirect
      readout interactions. Examples of indirect readout mechanisms in these complexes
      are DNA bending and non-local electrostatic complementarity. An intriguing
      question arising from these structures is the role that a series of lysine
      residues may have in DNA binding. Thus, in the yeast complex, seven lysines are
      found to be close to the phosphate backbone, but they appear to form hydrogen
      bonds to the protein and not to be involved in any direct (or water-mediated)
      interactions with the DNA. The proposal based on the crystal structure, that
      these residues set up a delocalized electrostatic potential that stabilizes the
      complex with DNA, is evaluated here from calculations of the electrostatic
      potentials generated by the wild-type TBP and various lysine to leucine mutants.
      The results suggest a grouping of these mutants into three classes, based on
      their phenotypes and electrostatic profiles. As these groups are affected
      differently by specific measures taken to rescue DNA binding and transcription
      functions, the mechanistic inferences from the analysis can be probed
      experimentally in a manner that also reveals possible binding sites for
      transcription factors IIA and IIB to the TBP-DNA complex in the transcription
      preinitiation complex.

PMID- 8532679
TI  - Modelling the three-dimensional structure and the electrostatic potential field
      of two Cu,Zn superoxide dismutase variants from tomato leaves.
AB  - The three-dimensional structure of tomato P31 and T10 Cu,Zn superoxide dismutases
      (SODs) were computer modelled using the structure of the bovine enzyme as a
      template. The structure-essential residues retain in the models the position
      occupied in the other Cu,Zn SODs of known 3D structure and the overall packing of
      the beta-barrel is maintained. Formation of 'aromatic pairs' occurs between newly
      inserted aromatic residues. The number of total charges changes in the two
      variants and some charged residues located in the proximity of the active site in
      most Cu,Zn SODs disappear in tomato enzymes. Calculation of the electrostatic
      potential field, carried out by numerically solving the Poisson-Boltzmann
      equation, indicates that in both variants a negative potential field surrounds
      all the protein surface except the active site areas, characterized by positive
      potential values, as already observed in the bovine enzyme. This result confirms
      that coordinated mutations of charged residues have occurred in the evolution of
      this enzyme giving rise to a peculiar electrostatic potential distribution common
      to all members of this protein family.

PMID- 8532680
TI  - Computer simulations of signal transduction mechanism in alpha 1B-adrenergic and
      m3-muscarinic receptors.
AB  - Molecular dynamics simulations of the hamster alpha 1B-adrenergic and the rat m3
      muscarinic seven-helix bundle receptor models have been carried out. The free,
      agonist-bound and antagonist-bound forms have been considered. Moreover, three
      mutant forms of the m3-muscarinic receptor (N507-->A, N507-->D and N507-->S) have
      also been simulated; among these, the N507-->S mutant shows a constitutive
      activity. A comparative structural/dynamics analysis has been performed to
      elucidate (i) the perturbations induced by the functionally different ligands
      upon binding to their target receptor, (ii) the features of the three single
      point mutants with respect to the receptor wild type and (iii) the properties
      shared by the agonist-bound forms of the alpha 1B-adrenergic receptor and the m3
      muscarinic receptor and by the constitutively active mutant N507-->S. The
      consistency obtained between the structural rearrangement of the transmembrane
      seven-helix bundle models considered, and the experimental pharmacological
      efficacies of the ligands and of the mutants, constitute an important validation
      of the 3-D models obtained and allow the inference of the mechanism of ligand- or
      mutation-induced receptor activation at the molecular level.

PMID- 8532681
TI  - Identifying the mechanism of protein loop closure: a molecular dynamics
      simulation of the Bacillus stearothermophilus LDH loop in solution.
AB  - The 'loop' involving residues 98-110 in Bacillus stearothermophilus lactate
      dehydrogenase (BSLDH) is of great interest as substrate-induced 'loop' closure is
      thought to be rate-limiting and essential in catalyzing the reaction and in
      determining substrate specificity. Consequently, we have explored the mechanism
      underlying 'loop' opening in BSLDH through a molecular dynamics simulation at
      high temperature (1000 K) in the presence of explicit solvent, starting from the
      X-ray structure of BSLDH complexed with the co-enzyme NAD+ and oxamate at 2.5 A.
      During the simulation, a significant conformational change occurred, as evidenced
      by sharp dihedral angle transitions, hydrogen bond breaking and formation and
      large root mean square deviations from the starting structure; these changes
      define the criteria for 'loop' opening. The mechanical elements responsible for
      'loop' opening, i.e. 'loop' hinges and flap, are defined through a combination of
      order parameters, dihedral angle changes and their correlations and the dynamical
      cross-correlation map of atomic displacements for the 'loop' residues. The
      results indicate that the 'loop' consists of two flexible hinge regions on either
      side of a relatively rigid three-residue segment that undergoes a significant
      spatial displacement during 'loop' opening. 'Loop' opening is made possible
      through an array of correlated dihedral angle changes and intra-'loop'
      rearrangements of hydrogen-bond interactions. The present findings are compared
      to previous work related to 'loop' opening and site-directed mutagenesis
      experiments.

PMID- 8532682
TI  - Identification and elimination by site-directed mutagenesis of thermolabile
      aspartyl bonds in Aspergillus awamori glucoamylase.
AB  - Both native Aspergillus niger glucoamylase and wild-type Aspergillus awamori
      glucoamylase expressed in Saccharomyces cerevisiae, which have identical primary
      structures, undergo hydrolysis at aspartyl bonds at low pH values and elevated
      temperatures. In native A.niger enzyme the Asp126-Gly127 bond was preferentially
      cleaved at pH 3.5, while at pH 4.5 cleavage of the Asp257-Pro258 and Asp293
      Gly294 bonds was dominant. In wild-type A.awamori glucoamylase, cleavage of the
      latter was dominant at both pH 3.5 and 4.5. Site-directed mutations Asp126-->Glu
      and Gly127-->Ala in wild-type enzyme decreased specific activities by
      approximately 60 and 30%, respectively, and increased irreversible
      thermoinactivation rates 3- to 4-fold at pH 4.5. Replacement of Asp257 with Glu
      and Asp293 with Glu or Gln decreased specific activities by approximately 20%,
      but greatly reduced cleavage of the Asp257-Pro258 and Asp293-Gly294 bonds. The
      Asp257-->Glu mutant was produced very slowly and was more thermostable than wild
      type glucoamylase at pH 4.5 up to 70 degrees C. Replacement of Asp293 with either
      Glu or Gln significantly raised protein production and slightly increased
      thermostability at pH 3.5 and 4.5, but not at pH 5.5.

PMID- 8532683
TI  - Citrate synthase from the hyperthermophilic Archaeon, Pyrococcus furiosus.
AB  - The gene encoding the enzyme citrate synthase has been cloned and sequenced from
      the hyperthermophilic Archaeon Pyrococcus furiosus, and the derived amino acid
      sequence has been phylogenetically compared with citrate synthases from archaeal,
      bacterial and eukaryal organisms. The gene has been over-expressed in Escherichia
      coli to produce an active enzyme that has then been characterized with respect to
      its kinetic, oligomeric and hyperthermostable properties. A structurally-based
      sequence alignment was made to the citrate synthase from the thermophilic
      Archaeon Thermoplasma acidophilum, the crystal structure of which we have
      determined recently. From this alignment, a homology-modelled structure for the
      P.furiosus citrate synthase was generated and analysed.

PMID- 8532684
TI  - Bacterial expression of Scapharca dimeric hemoglobin: a simple model system for
      investigating protein cooperatively.
AB  - Recombinant Scapharca homodimeric hemoglobin has been expressed at high levels
      from a synthetic gene in Escherichia coli. Addition of the heme precursor delta
      aminolevulinic acid to the expression culture results in a considerable increase
      in the yield of soluble hemoglobin. The recombinant hemoglobin exhibits
      cooperative oxygen binding properties indistinguishable from native protein.
      Crystals of the recombinant protein, like those of native hemoglobin, diffract to
      high resolution which will allow functional studies of site-directed mutants to
      be correlated with detailed structural analyses.

PMID- 8532685
TI  - A combinatorial library of an alpha-helical bacterial receptor domain.
AB  - The construction and characterization of a combinatorial library of a solvent
      exposed surface of an alpha-helical domain derived from a bacterial receptor is
      described. Using a novel solid-phase approach, the library was assembled in a
      directed and successive manner utilizing single-stranded oligonucleotides
      containing multiple random substitutions for the variegated segments of the gene
      fragment. The simultaneous substitution of 13 residues to all 20 possible amino
      acids was carried out in a region spanning 81 nucleotides. The randomization was
      made in codons for amino acids that were modelled to be solvent accessible at a
      surface made up from two of the three alpha-helices of a monovalent Fc-binding
      domain of staphylococcal protein A. After cloning of the PCR-amplified library
      into a phagemid vector adapted for phage display of the mutants, DNA sequencing
      analysis suggested a random distribution of codons in the mutagenized positions.
      Four members of the library with multiple substitutions were produced in
      Escherichia coli as fusions to an albumin-binding affinity tag derived from
      streptococcal protein G. The fusion proteins were purified by human serum albumin
      affinity chromatography and subsequently characterized by SDS-electrophoresis, CD
      spectroscopy and biosensor analysis. The analyses showed that the mutant protein
      A derivatives could all be secreted as soluble full-length proteins. Furthermore,
      the CD analysis showed that all mutants, except one with a proline introduced
      into helix 2, have secondary structures in close agreement with the wild-type
      domain. These results proved that members of this alpha-helical receptor library
      with multiple substitutions in the solvent-exposed surface remain stable and
      soluble in E. coli.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532687
TI  - Ethics and publishing in medical journals.

PMID- 8532686
TI  - Bacterial expression, purification and preliminary kinetic description of the
      kinase domain of v-fps.
AB  - The gene coding for the tyrosine protein kinase domain of v-fps was subcloned
      into a plasmid vector expressing glutathione-S-transferase (GST). This new vector
      expresses a fusion protein in Escherichia coli composed of the kinase domain
      linked with GST at the N-terminus (GST-kin). A portion of the total expressed
      protein was soluble upon cell lysis and was purified by affinity chromatography
      using glutathione cross-linked agarose. GST-kin (M(r) 57,000) is a phosphoprotein
      as judged by 32P autoradiography, consistent with the known autophosphorylation
      site within the kinase core [Weinmaster et al. (1984) Cell, 37, 559-568].
      Cleavage of the fusion protein with thrombin and purification on phosphocellulose
      resin yielded the pure kinase domain (M(r) 33,000). The activity of the kinase
      domain is indistinguishable from that of GST-kin using the peptide substrate
      EEEIYEEIE, indicating that N-terminal fusion has no effect on the kinase domain.
      GST-kin phosphorylates a second peptide, EAEIYEAIE, with improved catalytic
      efficiency. Initial velocity data are consistent with a random bireactant
      mechanism with no substrate synergism observed in the ternary complex. Steady
      state kinetic analyses reveal that this peptide is phosphorylated, with a kcat of
      3.6 s-1, a Kpeptide of 500 microM and a KATP of 250 microM. The expression,
      purification and preliminary kinetic analysis of the kinase domain of v-fps
      provide the first step in the application of structure-function studies for this
      oncoprotein.

PMID- 8532688
TI  - Lewis X antigen immunostaining in the diagnosis of transitional cell carcinoma.
AB  - Immunodetection of the Lewis X antigen has been suggested as a useful adjunct in
      the diagnosis of transitional cell carcinoma. To determine the specificity of
      Lewis X antigen immunostaining in this setting, we studied routinely processed,
      formalin-fixed tissue from 38 transitional cell carcinomas and 42 nonneoplastic
      urothelial lesions using the P12 monoclonal antibody to Lewis X antigen and an
      avidin-biotin immunohistochemical technique. Because Lewis X immunostaining of
      occasional umbrella cells has previously been noted in normal urothelium,
      staining of umbrella cells was not considered sufficient for a positive reaction
      in our study. Immunoreactivity for Lewis X antigen was seen in 34 of 38 (89%)
      cases of transitional cell carcinoma, in three of three cases of urothelial
      dysplasia, and in 20 of 39 (51%) of the reactive urothelial lesions. We conclude
      that immunostaining for the Lewis X antigen is not specific in the diagnosis of
      transitional cell carcinoma.

PMID- 8532689
TI  - Morphologic and neuroendocrine features of adenocarcinoma arising in the
      transition zone and in the peripheral zone of the prostate.
AB  - We examined retrospectively 107 step-sectioned radical prostatectomy specimens.
      The index tumor in each specimen was designated a transition zone carcinoma
      (TZCa) or a peripheral zone carcinoma (PZCa) based on its location. All tumor
      sections were immunohistochemically stained with chromogranin A (ChrA). A
      semiquantitative ChrA score (0 to 3) was assessed. ChrA-positive neuroendocrine
      cells were found in 83% of the index tumors. The ChrA score was significantly
      related to the Gleason score, the volume of the tumor, and the pathologic stage.
      Twenty-two percent of the index tumors were designated TZCas; 75% of these
      demonstrated neuroendocrine differentiation versus 85% of the PZCas. A high ChrA
      score of > or = 2 was found in 46% of PZCas and in only 33% of TZCas. Capsular
      transgression, seminal vesicle involvement, positive surgical margins, and lymph
      node metastasis were seen in the TZCa group in 33%, 17%, 29%, and 4%,
      respectively versus 58%, 20%, 48%, and 6% in the PZCa group. These findings were
      associated with a higher mean tumor volume in the TZCa group compared with the
      PZCa group. The average Gleason score of 4.5 in the TZCa group was significantly
      (P < 0.0001) lower than the Gleason score 6.2 in the PZCa group. Multicentricity
      was found in 62% of TZCas and in 49% of PZCas. Eighty-seven percent of the second
      tumors in the prostates with a primary TZCa were located in the peripheral zone.
      We conclude that the frequently occurring neuroendocrine cells population
      enlarges with tumor progression, especially in PZCas.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8532690
TI  - Rectal endometriosis mimicking solitary rectal ulcer syndrome.
AB  - We report a unique case of rectal endometriosis mimicking solitary rectal ulcer
      syndrome. Several rectal biopsies were performed before the correct diagnosis of
      rectal endometriosis was made. The lesion had striking histologic features
      resembling colitis cystica profunda. The presence of two types of glands, i.e.,
      colonic glands with marked depletion of mucin and endometrial glands, were
      readily apparent on immunohistochemical stain using anticarcinoembryonic antigen
      showing positive cytoplasmic stain for colonic glands but negative for
      endometrial glands. However, the distinction between colonic and endometrial
      glands was very difficult on hematoxylin-and-eosin-stained slides. Endometrial
      stroma was identified only in the sixth biopsy specimen. Although rare, rectal
      endometriosis should be considered in the differential diagnosis of solitary
      rectal ulcer syndrome.

PMID- 8532691
TI  - Low-grade papillary adenomatous tumors of the temporal bone: report of two cases
      and review of the literature.
AB  - Two cases of tumors of the posterior portion of the petrous bone are presented.
      Both resulted in significant loss of hearing and caused extensive bone
      destruction. Microscopically, they corresponded to papillary adenomatous tumors
      with few histologically aggressive features. Immunohistochemical studies were
      done, and a positive reaction was obtained with the antibodies against the
      cytokeratins, Leu-7 and neuronal-specific enolase. A diagnosis of adenocarcinoma
      of the endolymphatic sac was made. These are rare tumors known for their long
      clinical prodrome and their local aggressiveness. Increased awareness will allow
      for earlier diagnosis and treatment.

PMID- 8532692
TI  - Postinfarct cardiac free wall rupture: the relationship of rupture site to
      papillary muscle insertion.
AB  - The objective of this study was to examine for any relationship between the sites
      of papillary muscle insertion in left ventricular free wall (LVFW) and the site
      of LVFW rupture postinfarct. Twenty-five consecutive patients with LVFW rupture
      (12 men and 13 women, mean age 72.3 yr, range = 48 to 93) at the University of
      Ottawa Heart Institute during the period of July 1, 1988 to 1992 were studied.
      Clinical charts were reviewed, and the Formalin-fixed hearts were re-examined
      grossly and microscopically. Each patient died of tamponade or after surgery for
      tamponade. Eight (32%) of the 25 infarcts were anteroseptal or anterior, 11 of 25
      (44%) were lateral, and 6 of 25 (24%) were inferior or inferoseptal. Four (16%)
      of the 25 infarcts were less than 2 days old, 9 of 25 (36%) were 2 to 5 days old,
      and 12 of 25 (48%) were 5 to 10 days old. A separate pre-existent and healed
      infarct was noted in 36% of patients; however, rupture adjacent to these areas of
      old infarct occurred in only 8% of cases. In 15 of 25 (60%) cases, free wall
      rupture occurred in the lateral wall between and at the level of the two
      papillary muscles. In a further 5 of 25 (20%) cases, the rupture was beside one
      of the papillary muscles but in anterior or posterior walls. In 20 of 25 (80%)
      cases, the endocardial tear associated with the LVFW rupture was within 1 cm of
      the base of one of the papillary muscles as they inserted in LVFW.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8532693
TI  - Malignant mesothelioma associated with low pulmonary tissue asbestos burdens: a
      light and scanning electron microscopic analysis of 18 cases.
AB  - Most malignant mesothelioma cases are associated with pulmonary asbestos body
      (AB) counts significantly greater than those of the general population. However,
      the question remains whether malignant mesothelioma cases associated with
      "normal" AB counts (i.e., indistinguishable from the general population)
      represent background incidence levels or are, actually, asbestos related. We
      performed AB counts (by light microscopy) and mineral fiber analysis (by scanning
      electron microscopy) in 18 mesothelioma cases with AB counts within our normal
      range (0 to 20 AB/G wet lung) and in 19 "control" cases. Our study demonstrated
      that approximately one-third (6 of 18) of the mesothelioma cases have asbestos
      fiber burdens greater than 95% of the control levels. These results suggest that
      these six mesothelioma cases may be asbestos related despite AB counts similar to
      those of the general population. An asbestos etiology was suggested in three
      additional cases, but too few amphibole fibers were identified in these cases to
      be certain of a value above background. The remaining nine cases showed no
      evidence of an asbestos etiology. Electron microscopic analysis of pulmonary
      mineral fibers may be required to differentiate asbestos-related mesotheliomas
      from non-asbestos-related cases when AB counts are within the range of background
      values.

PMID- 8532694
TI  - Seminomas positive for Epstein-Barr virus by the polymerase chain reaction: viral
      RNA transcripts (Epstein-Barr-encoded small RNAs) are present in intratumoral
      lymphocytes but absent from the neoplastic cells.
AB  - A possible role of Epstein-Barr virus (EBV) in the pathogenesis of testicular
      germ cell neoplasms has been suggested repeatedly, but direct evidence for an
      association of testicular cancer with EBV is lacking. We examined 26 cases of
      classical seminoma, two spermatocytic seminomas, and 12 cases of nonseminomatous
      or combined germ cell tumors for the presence and cellular location of EBV with a
      combined approach using the polymerase chain reaction and nonradioactive in situ
      hybridization for EBV-encoded small RNAs (EBER1/2). After exclusion of cases
      without amplifiable DNA, 4/21 (19%) seminomas, but none of the other tumors, were
      positive for EBV by polymerase chain reaction. In situ hybridization for EBER1/2
      showed rare positive lymphocytes, probably latently infected B-cells, in two of
      these four EBV-positive cases. No EBER-positive tumor cells were found in any of
      the analyzed tumors. The occurrence of EBV-positive lymphoid cells was not
      correlated to the frequency of intratumoral lymphocytes, including B-cells, which
      were present in seminomas in significant numbers. Our study demonstrates the
      absence of EBV from the neoplastic cells of testicular germ cell tumors and makes
      a direct role of EBV in the development of these malignancies improbable. Whether
      the presence of EBER-positive lymphocytes in some seminomas simply reflects the
      normal occurrence of latently infected cells in lymphoid tissue of seropositive
      individuals or is influenced by local factors remains to be determined.

PMID- 8532695
TI  - Chromogranin gene expressions in colorectal adenocarcinomas.
AB  - Presence of neuroendocrine (NE) cells identified by argyrophilia and presence of
      NE markers, such as the chromogranins) is a common event (15 to 51% of the cases)
      in colorectal adenocarcinomas. The nature and significance of these cells,
      scattered in variable number within the neoplastic population, is unclear. Twenty
      five cases of colorectal adenocarcinomas were investigated in parallel by
      immunocytochemical and hybridization (Northern blot) procedures to detect
      presence of three members of the chromogranin family, i.e., Chromogranin A,
      Chromogranin B, and Secretogranin II/secretoneurin and their synthetic machinery.
      The results indicate discrepancies between presence of immunoreactive cells and
      expression of the related specific mRNA molecules. Interestingly, such
      discrepancies were more remarkable for Chromogranin A than for Chromogranin B and
      Secretogranin II. Taking into account all three types of chromogranins, only a
      few cases provided the same results at the mRNA and protein levels investigated
      respectively by Northern blot and immunohistochemistry. The spectrum of observed
      events is therefore wider and more complex than hitherto believed. Our
      interpretation is that transient activation of NE differentiation genes can be a
      common and extensive event in neoplastic stem cells. In a few postmitotic cells,
      expression of NE genes would lead to cytoplasmic accumulation of NE markers and
      regulatory peptides, retained even after the switching off of the genes. This
      hypothesis might be valid for various mixed exocrine-endocrine patterns observed
      in carcinomas of different organs (gastrointestinal tract, pancreas, prostate,
      breast, lung).

PMID- 8532696
TI  - Coexistence of nipple duct adenoma and breast carcinoma: a clinicopathologic
      study of five cases and review of the literature.
AB  - The simultaneous occurrence of nipple duct adenoma (NDA) and carcinoma in the
      same breast is rare and generally considered an incidental finding. Five examples
      of such concurrent lesions are reported. The patients ranged in age from 48 to 70
      y, and they all presented with a palpable mass that was subareolar in three and
      in the lower inner quadrant in two women. The presence of distorted nipple with
      discharge in two patients and nipple erosion in another had raised the
      possibility of Paget's disease clinically. Microscopically, an infiltrating duct
      carcinoma was present in four women and an intraductal carcinoma in the fifth-
      all along with a NDA. Two of the invasive carcinomas were adjacent to the NDA and
      immediately beneath the surface epithelium of the nipple; the NDA in one of these
      had atypical intraductal hyperplasia. Three women had mastectomy and axillary
      node dissection, two had excisional biopsy only. Follow-up was available in four
      women and ranged from 1.5 to 8 y. One of these women developed metastasis and
      died 8 y postdiagnosis; the remaining three are alive and well. In at least three
      cases, the invasive carcinoma was not suspected clinically, and the initial
      procedure was done because of symptomatology secondary to the NDA.

PMID- 8532697
TI  - Correlations of morphology, proliferation indices, and oncogene activation in
      ductal breast carcinoma: nuclear grade, S-phase, proliferating cell nuclear
      antigen, p53, epidermal growth factor receptor, and c-erb-B-2.
AB  - The proliferative capacity of breast carcinomas has prognostic significance as
      measured by S-phase fraction (SPF), yet the molecular parameters that influence
      the proliferative capacity of breast carcinomas have not been fully elucidated.
      Ninety-three cases of invasive ductal breast carcinomas, not otherwise specified,
      were studied by immunohistochemistry and flow cytometry to determine what
      correlations exist between nuclear grade (NG), SPF, proliferating cell nuclear
      antigen and the overexpression of p53, epidermal growth factor receptor (EGFR),
      and c-erb-B-2 in formalin-fixed tissues by the immunoperoxidase method. NG
      predicted elevated SPF in 78% of cases and was associated with high proliferating
      cell nuclear antigen score. The presence of p53 was detectable in 13% of cases,
      and, in each case, the NG was high (Grade 3), with nine aneuploid tumors and
      three diploid tumors. The SPFs for all p53-positive cases were markedly elevated,
      with 77.8% of the cases with SPF > 15%. EGFR was present in 20.4% of all tumors,
      including 77.8% of tumors positive for p53 and 14% of tumors negative for p53 (P
      < .001). The mean SPF for p53-positive EGFR-positive tumors was 17.5% versus
      21.1% for p53-positive EGFR-negative tumors. The mean SPF for p53-negative tumors
      was significantly less, regardless of the presence of EGFR. The gene c-erb-B-2
      was found in 28% of tumors, all of which were p53 negative. These data clearly
      show a close relationship between high NG and elevated SPF. As determined by flow
      cytometry, SPF is more consistent and more reliably related to NG than
      proliferating cell nuclear antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532698
TI  - Immunohistochemical staining and Southern blot hybridization for glutathione S
      transferase pi in mammary infiltrating ductal carcinoma.
AB  - Glutathione S-transferase pi, a drug-detoxifying isoenzyme of potential
      prognostic value for subsets of patients with mammary cancer, was studied by
      immunohistochemistry and Southern blot analysis in 58 infiltrating ductal
      carcinomas. The results were compared with the findings of six important
      clinicopathologic parameters. Cytoplasmic immunoreactivity for glutathione S
      transferase pi was absent in 40%, 1+ in 26%, 2+ in 15%, and 3+ in 19% of the
      cases. There were no significant correlations between the level of immunostaining
      and patient age, tumor size, axillary lymph node status, nuclear pleomorphism, or
      tubule formation, but there was a trend with mitotic count (P = 0.06).
      Immunoreactivity was associated with histologic grade (P = 0.02) and inversely
      correlated with estrogen (P = 0.006) and progesterone (P = 0.02) receptor
      content. Ten percent of the cases showed modest levels of glutathione S
      transferase pi gene amplification, but no significant correlations were observed
      between glutathione S-transferase pi amplification and any of the
      clinicopathologic parameters or level of immunostaining. The results indicate
      that increased immunohistochemical staining for glutathione S-transferase pi
      occurs in high-grade, estrogen and progesterone receptor-negative neoplasms. As
      glutathione S-transferase pi gene amplification appears unassociated with
      immunopositivity, other mechanisms are responsible for the production of this
      isoenzyme in infiltrating ductal carcinomas.

PMID- 8532699
TI  - Epithelial proliferation and differentiation in flat duodenal mucosa of patients
      with familial adenomatous polyposis.
AB  - The colonic mucosa in patients with familial adenomatous polyposis (FAP) exhibits
      altered epithelial cell proliferation, differentiation, and mucin histochemical
      properties compared with unaffected controls. However, little is known regarding
      these parameters in FAP-associated duodenal mucosa, an area in which adenomas
      also develop at a high rate. The purpose of this study is to evaluate the
      morphologic, mucin histochemical, and proliferative characteristics of the
      epithelium in the flat duodenal mucosa from 32 patients with FAP (18 with and 14
      without adenomas), and compare the results with those observed in 18 non-FAP age
      matched controls. The proliferative properties of the epithelium were analyzed
      immunohistochemically with the MIB-1 antibody, which recognizes the Ki-67
      proliferation-associated nuclear antigen in formalin-fixed tissue. No significant
      differences were detected with regard to the mucin histochemical properties
      (sialomucins, sulfomucins, and o-acylated sialomucins) or the proliferative
      characteristics of the duodenal epithelium in FAP versus non-FAP controls.
      However, FAP-associated duodenal epithelium showed a significant increase in the
      number of Paneth cells (P = 0.04) and endocrine cells (P = 0.01) per crypt in
      comparison with controls. This specialized cell hyperplasia occurred in the flat
      mucosa of FAP patients regardless of the presence or absence of adenomas and may
      represent a primary defect in the regulation of stem cell differentiation in the
      duodenum in FAP.

PMID- 8532700
TI  - Expression of p53 antigen in inflamed and regenerated mucosa in ulcerative
      colitis and Crohn's disease.
AB  - Physiologic overexpression of p53 protein may occur in the G1 stage of the cell
      cycle to slow down the cell cycle and allow DNA repair in stressed or injured
      cells. We questioned whether there is increased expression of p53 protein in
      acutely inflamed mucosa (AI) and regenerated mucosa (RM) in ulcerative colitis
      (UC) and Crohn's disease (CD). Formalin-fixed paraffin-embedded sections of
      resected bowels from eight patients with UC and 20 with CD were reviewed, and
      blocks were selected having areas defined as follows: AI = two high-power fields
      (HPFs) at the edge of an ulcer, or one HPF with an inflamed crypt in the center;
      RM = branched or irregular glands with only mild chronic inflammation. Blocks
      with normal mucosa were available in 20 cases. One case of CD also had dysplasia,
      adenoma, and invasive carcinoma. p53 was identified with PAb1801 antibody using a
      labeled avidin-biotin immunoperoxidase technique. In each defined area, the
      positive nuclei were counted and expressed as the number of positive nuclei per
      10 HPFs. Data were analyzed statistically for comparisons within and between the
      diseases. In normal mucosa, only rare cells expressed p53 in two cases of CD. The
      mean frequency of positive nuclei was 2.24/10 HPFs in AI and 0.30/10 HPFs in RM
      in CD, and 7.63/10 HPFs in AI and 1.14/10 HPFs in RM in UC. Differences between
      the means for AI and RM were statistically significant in both UC and CD.
      Although not significant, the frequency of positive staining in both AI and RM
      was greater in UC as compared with CD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532701
TI  - Primary pulmonary rhabdomyosarcomas: a clinicopathologic and immunohistochemical
      study of three cases.
AB  - Three cases of primary pulmonary rhabdomyosarcoma in adults are presented. The
      patients were all men between the ages of 57 and 78 yr (mean 67.5). All patients
      presented with symptoms referable to their tumors, including cough, shortness of
      breath, pleuritic chest pain, and weight loss. In one patient, a history of
      tobacco and alcohol abuse was obtained. Anatomically, two tumors were located in
      the left upper lobe and one in the left lower lobe. Grossly, the tumors ranged in
      size from 6 to 11.5 cm and were tan-gray, firm masses with areas of necrosis and
      hemorrhage. Histologically, the tumors were characterized by a spindle cell
      proliferation admixed with areas showing a pleomorphic cell population with
      numerous rhabdomyoblasts and areas of hemorrhage and necrosis.
      Immunohistochemically, all three tumors showed strong positivity with desmin and
      myoglobin antibodies and negative staining with antibodies against keratin,
      epithelial membrane antigen, and S-100 protein. All patients had a fatal outcome.
      Two patients died a few days after admission with respiratory distress; the third
      one died 2 years after diagnosis with widely metastatic disease. Autopsy findings
      in all cases disclosed disseminated metastases to multiple abdominal and thoracic
      organs. Primary pulmonary rhabdomyosarcoma should be considered in the
      differential diagnosis of poorly differentiated pulmonary neoplasms in adults and
      should be distinguished from other primary and metastatic sarcomas.

PMID- 8532702
TI  - Leprosy in five human immunodeficiency virus-infected patients.
AB  - We present five cases of leprosy in five human immunodeficiency virus-positive
      individuals. The patients were five men between the ages of 18 and 45 years. The
      five patients presented with skin lesions; three patients with hypopigmented skin
      lesions, one with skin macules and a history of leprosy, and one with papular
      lesions. In one patient, there was bilateral "claw hands." Histologically, two
      cases were categorized as lepromatous leprosy, two as borderline tuberculoid, and
      one as borderline lepromatous. Follow-up information obtained in the five
      patients showed one patient had died, and the remaining four patients were alive
      and receiving antileprosy treatment.

PMID- 8532703
TI  - Biologic and clinical significance of basic fibroblast growth factor
      immunostaining in breast carcinoma.
AB  - Acetone-fixed cryostat sections of 79 breast carcinomas were immunostained with
      antibodies to basic fibroblast growth factor (bFGF) and urokinase-type
      plasminogen activator (uPA). Staining intensity was then compared with
      microvessel density assessed by manually counting vascular spaces highlighted by
      immunostaining vascular basal lamina (Type IV) collagen. Extensive (2+) bFGF
      immunoreactivity was present in neoplastic cells of 30 tumors (38%) and in host
      derived stromal cells of 29 cases (37%). Disease recurrence correlated with bFGF
      staining: 0 to 1+ stromal staining, 30% recurred versus 2+ stromal staining, 73%
      recurred (P = 0.001) (54-mo median follow-up). Neither stromal nor epithelial
      bFGF staining correlated significantly with microvessel count; however, there was
      a statistically significant association between stromal cell bFGF staining and
      uPA staining of peritumor host cells: absent bFGF--0% 2+ uPA versus weak bFGF--9%
      2+ uPA versus 2+ bFGF--29% uPA (P = 0.01). We conclude that elevated expression
      of bFGF in breast carcinomas is associated with aggressive clinical behavior. Its
      biologic significance, however, appears more closely related to extracellular
      matrix remodeling than to induction of prominent neovascularization per se.

PMID- 8532704
TI  - Extramedullary hematopoiesis in the allograft liver.
AB  - The clinicopathologic correlates of extramedullary hematopoiesis were studied in
      77 allograft biopsies from 27 patients who underwent liver transplantation for
      end-stage liver disease. The patient cohort consisted of 19 men and 8 women,
      ranging in age from 23 to 75 yr (median 41). The causes of end-stage liver
      disease included viral hepatitis (n = 20), ethanol abuse (n = 6), and congenital
      hepatic fibrosis (n = 1). Most patients (23 of 27) had significant septic
      complications in the postoperative period. The hematocrit was typically low (25
      to 31%), and a history of allograft hepatectomy with retransplantation was
      available in 10 of 27 (37%) patients. Extramedullary hematopoiesis was first
      diagnosed 5 to 461 days (median 275) post-transplant and persisted 7 days to 36
      mo (median 1 mo) thereafter. Pathologic findings concurrent with extramedullary
      hematopoiesis were acute cellular rejection/central venulitis (n = 7), ischemic
      preservation injury (n = 10), chronic rejection (n = 5), and chronic
      hepatitis/cirrhosis (n = 5). The pathogenesis of extramedullary hematopoiesis in
      these cases is not clear, but a low hematocrit may have been a stimulant for the
      observed hematopoiesis. In addition, the frequent coexistence of infectious,
      immunologic, or ischemic injury within the allograft suggests that reparative
      responses can stimulate intrahepatic stem cells to undergo hematopoietic
      differentiation. The cytokines likely involved in this process are discussed.

PMID- 8532705
TI  - Association of Epstein-Barr virus latent membrane protein and Hodgkin's disease
      in Mexico.
AB  - Epstein-Barr virus (EBV) has been demonstrated in association with Hodgkin's
      disease (HD) in approximately 40 to 50% of cases in series from North America,
      Europe, and Japan. However, few data are available concerning this association in
      developing countries. Recent studies, including mostly a pediatric population
      from Peru and a pediatric population from Honduras, showed a higher percentage of
      EBV positivity compared with those in developed countries. To determine the
      prevalence of EBV in Hodgkin's disease in a Mexican adult population, we analyzed
      50 formalin-fixed, paraffin-embedded cases of HD by a three-step technique using
      a monoclonal antibody to the latent membrane protein of EBV. All the cases were
      confirmed immunophenotypically as HD (CD15+ and/or CD30+, CD45-). Reed-Sternberg
      cells and variants were positive for LMP in 35 cases (70%). The staining was
      found both on the cell surface and/or within the cytoplasm with enhancement of
      the Golgi area. EBV latent membrane protein was found in 1/1 case (100%) of
      diffuse lymphocyte-predominant HD, 10/20 cases (50%) of nodular-sclerosis, 18/22
      cases of mixed-cellularity (81%), and 6/7 (86%) cases of lymphocyte-depleted HD.
      Our results show a high prevalence of EBV in HD in this Mexican adult population.
      All histologic subtypes of HD in the population analyzed appear to be strongly
      associated with EBV, in contrast to the strong association of mixed cellularity
      HD in developed countries. Patient age and gender were not predictive of the
      presence of EBV.

PMID- 8532706
TI  - The relationship of granulomas to blood vessels in intestinal Crohn's disease.
AB  - It has been suggested that granulomatous vasculitis is a primary mechanism in the
      production of pathologic changes seen in Crohn's disease. We set out to
      investigate the relationship of granulomas to blood vessels and to confirm or
      refute previous reports of granulomatous vasculitis in Crohn's disease. Thirty
      paraffin embedded tissues from 11 patients with Crohn's disease were selected
      after examination of H&E stained sections for the presence of granulomas. Using
      an immunohistochemical method, various monoclonal antibodies were applied to
      sequential sections from each tissue to demonstrate vascular structures and
      granulomas. In three patients none of the granulomas occurred in association with
      blood vessels, in five a small proportion of the granulomas affected blood
      vessels, and in three granulomatous vasculitis appeared occlusive and
      significant. A total of 232 granulomas were identified, 22% of which were closely
      associated with blood vessels, which included both arteries and veins; 16% were
      perivascular, while 6% were intravascular. Perivascular granulomas did not
      surround blood vessels or invade the medial layers. They were asymmetric,
      suggesting that they originated by encroachment of nearby lymphatic or connective
      tissue granulomas. These results indicate that the granulomas of Crohn's disease
      are usually not associated with blood vessels; however, there is a minority of
      patients in whom vascular granulomatous inflammation may be important, although
      probably as a secondary phenomenon.

PMID- 8532707
TI  - Multiparameter flow cytometric DNA analysis of effusions: a prospective study of
      36 cases compared with routine cytology and immunohistochemistry.
AB  - Single-parameter flow cytometry (SFCM) is limited in its ability to detect
      aneuploid and diploid malignant cells or accurately estimate S-phase fractions
      (SPF) in effusions because of the high degree of contamination by benign
      mesothelial cells and inflammatory cells. We examined 36 pleural and peritoneal
      fluids by conventional cytology and multiparameter FCM (MFCM) to analyze the DNA
      content of cells expressing epithelial markers cytokeratin, epithelial membrane
      antigen, carcinoembryonic antigen, BRST-1, or BRST-3 (B72.3) and compared the
      results to those found with SCFM. The cases were also studied by
      immunohistochemistry using the same antibody panel. By routine cytology, 14 of
      the 36 cases were classified as carcinomas, 11 as reactive, 1 as mesothelioma,
      and 10 as suspicious. MFCM allowed reclassification of 5 of the 10 suspicious
      cases as carcinomas and the remaining 5 as reactive cases based on ploidy and
      marker expression. Whereas SFCM detected only 13 nondiploid carcinomas, MFCM
      detected 4 diploid and 15 nondiploid carcinomas. All reactive cases were diploid
      by SFCM or MFCM. The mesothelioma case showed were distinct peaks by MFCM, a
      diploid peak with SPF of 13.4% and a tetraploid peak with SPF of 36.1%. The SPF
      of the nondiploid carcinomas ranged from 5.9 to 50.4% and diploid carcinomas,
      from 3.5 to 14.5% when gated on epithelial cells. The reactive cases had SPF
      ranging from 0.4 to 4.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532708
TI  - Skin carcinogenesis: characteristics, mechanisms, and prevention.
AB  - Skin carcinogenesis can be operationally and mechanistically divided into at
      least three major stages - initiation, promotion and progression. Variations
      among stocks and strains of mice to susceptibility to multistage skin
      carcinogenesis appear to be more related to alterations in tumor promotion than
      tumor initiation; however, the critical events have not been determined. In the
      mouse skin model the first stage is thought to involve the interaction of a tumor
      initiator with the genetic material of stem cells leading to an irreversible
      alteration in some aspect of growth control and/or differentiation, probably
      activating the Ha-ras oncogene. Some skin tumor promoters such as the phorbol
      esters, indole alkaloids, and polyacetates, appear to act through protein kinase
      C leading to specific phosphorylation of cellular proteins whereas others such as
      okadaic acid class of compounds appear to act through phosphatases also leading
      to an increase in phosphorylation. In addition, other types of tumor promoters
      such as peroxides, benzo(e)pyrene, and chrysarobin may act through a free radical
      mechanism. Regardless of the type, the major effect of the skin tumor promoters
      appears to be the specific expansion of the initiated stem cells in the skin.
      There is a very good correlation between the abilities of tumor promoters to
      induce a sustained hyperplasia and their tumor promoting activities. This appears
      to occur by both direct and indirect mechanisms involving the loss of
      glucocorticoid receptors, differentiation alterations, a direct growth
      stimulation of the initiated cells and/or selective cytotoxicity. A number of
      growth factors have recently been found to be increased during tumor promotion
      and may be responsible for the increase in cell proliferation. An inhibition of
      cell-cell communication and stimulation of differentiation of non-initiated cells
      appear to be important indirect mechanisms of further expanding the initiated
      cell population. The appearance of GGT and keratin 13 (K13) and the lack of
      expression of K1 and K10 were found to be good markers for skin tumor
      progression. These alterations occur at the time papillomas change from a diploid
      to aneuploid state which is mainly due to trisomies of chromosome 6 and 7. In
      order to evaluate a casual role for GGT in skin tumor progression, a functional
      GGT cDNA was transfected into two of our cell lines which normally produce
      papillomas when grafted into the skin of nude mice. The GGT positive cells and
      the vector transfected cells (controls) from one of the cell lines were cloned
      and injected into nude mice and placed into transplantation chambers.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8532709
TI  - Role of reactive intermediates in tumor promotion and progression.
AB  - Many tumor promoters, including the phorbol esters, do not require
      biotransformation to stimulate cell growth. By contrast, some promoters, notably
      organic peroxides and hydroperoxides, must be metabolized to reactive
      intermediates to trigger signal transduction pathways for mitogenesis. These
      intermediates can be both free radicals and electrophiles. For example, skin
      tumor promoters such as tert-butyl hydroperoxide, cumene hydroperoxide, dicumyl
      peroxide and benzoyl peroxide undergo metal-dependent activation in keratinocytes
      to form alkoxyl, alkyl and aryl radicals as determined by spin trapping and
      electron paramagnetic resonance spectroscopy. These radicals can participate in
      substitution, addition or hydrogen-abstraction reactions leading to protein
      oxidation or alkylation, lipid peroxidation and/or DNA damage. Scavenger studies
      indicate that these macromolecular interactions mediate the cytotoxic and
      mitogenic effects of these peroxides. In some instances radicals can undergo
      further oxidation to electrophiles. The promoting activity of butylated
      hydroxytoluene hydroperoxide is mediated by a quinone methide, an electrophile
      formed through a phenoxyl radical intermediate. In this instance, covalent
      interaction of the quinone methide with sulfhydryl groups or other nucleophiles
      in the target cell appears to transmit the molecular signal for cell division and
      replication. Like the phorbol esters, peroxides and hydroperoxides lead to a
      genetic reprogramming manifest by the induction of immediate early response genes
      such as c-jun and late response genes such as ornithine decarboxylase, suggesting
      convergence in the molecular signalling processes among different classes of
      promoters.

PMID- 8532710
TI  - The tumor promoter receptor protein kinase C: a novel target for chemoprevention
      and therapy of human colon cancer.
AB  - The high affinity receptor of phorbol-ester and related tumor promoters is the
      isozyme family protein kinase C (PKC). Activation of PKC by the phorbol esters is
      a pivotal event in phorbol ester-mediated tumor promotion. PKC activation is also
      implicated in tumor promotion of colonic epithelial cells by endogenous and
      dietary factors such as bile acids, free fatty acids, and diacylglycerols,
      suggesting that suppression of the inappropriate activation of colonic epithelial
      PKC by these factors could be an effective strategy of chemoprevention. Phorbol
      ester tumor promoters induce pleiotropic resistance against anti-cancer drugs in
      cultured human colon cancer cells. By characterizing PKC isozyme expression in
      the cells and the induction of resistance by isozyme-selective PKC activators, we
      have obtained evidence that the induction of resistance is triggered by phorbol
      ester activation of cPKC-alpha. We have also found that cPKC-alpha is expressed
      abundantly in surgical specimens of human colon cancer, indicating that cPKC
      alpha-mediated drug resistance may contribute to the intrinsic drug resistance of
      clinical colon cancer. The intrinsic resistance of human colon cancer to multiple
      anticancer drugs precludes effective therapy of disseminated disease with
      available chemotherapeutic regimens. The development of reversal agents of
      intrinsic drug resistance that function by selective inhibition of cPKC-alpha
      might allow successful management of the disease with standard cytotoxic
      chemotherapeutic regimens.

PMID- 8532711
TI  - Calcium, cell death, and tumor promotion.

PMID- 8532712
TI  - Transforming growth factor-beta s in mammary tumorigenesis: promoters or
      antipromoters?

PMID- 8532713
TI  - Liver tumor promotion: a process of natural selection.

PMID- 8532714
TI  - The pro-inflammatory and hyperplasiogenic action of interleukin-1 alpha in mouse
      skin.

PMID- 8532715
TI  - HGF in liver regeneration and tumor promotion.

PMID- 8532716
TI  - Hormonal and genetic interactions in murine hepatocarcinogenesis.

PMID- 8532717
TI  - Genetic factors controlling responsiveness to skin tumor promotion in mice.
AB  - Two genetic models that could explain all of the current data are depicted in
      Figure 4, although it should be stressed that proof of any model will require
      additional genetic analyses. The first model (Model A) indicates that one or more
      loci controlling responsiveness to TPA are also responsible for directly
      controlling responsiveness to other classes of skin tumor promoters such as BzPo
      and Chr. We have called this locus the Pms locus (for skin tumor promotion
      sensitivity). The differences between compounds in the magnitude of their
      promoting ability may reside in the inability to activate a full set or
      compliment of Pms loci. Genetic differences may reside in a critical Pms locus
      that is necessary for tumor promotion by all chemical promoters. Alternatively,
      the current data could be interpreted as showing that different genes responsible
      for high sensitivity to promotion by diverse promoting agents act on a pathway(s)
      common to promotion in mouse epidermis (Model B). In this case, the Pms locus
      would represent a common biochemical/molecular pathway where different responses
      mediated by different types of promoters ultimately converge and lead to the
      process of tumor promotion in mouse skin. Directly testing either of the above
      models will require analyses of progeny from appropriate segregating crosses
      among the various stocks and strains used in the present study. Model B could
      help explain several experimental observations. First, SSIn mice, while still
      retaining a fairly high sensitivity to skin tumor promotion with Chr relative to
      other inbred strains (i.e., DBA/2, C57BL/6), have lost their increased
      sensitivity to this anthrone derivative relative to SENCAR mice. SSIn were
      developed through a process of inbreeding starting with the current outbred
      SENCAR and employing a selection scheme using DMBA initiation and TPA promotion
      similar to that originally devised by Boutwell (1964). Second, C57BL/6 mice,
      although relatively resistant to TPA, chrysarobin and BzPo, are somewhat peculiar
      in their high resistance to standard promotion protocols using TPA (DiGiovanni et
      al., 1991). Indirectly, these observations suggest that different genes may
      regulate some responses to particular types of promoting agent. For example,
      perhaps the induction of a oxidant response by phorbol esters would represent a
      specific response to this class of tumor promoters. A testable prediction from
      these observations is that it may be possible to selectively breed for mouse
      lines more sensitive and/or resistant to specific classes of promoting agents.

PMID- 8532718
TI  - The instability of tumor promotion in relation to human cancer risk.

PMID- 8532719
TI  - Hepatocarcinogenesis in transgenic mice.
AB  - Transgenic mouse models of altered hepatic gene expression have provided a new
      set of tools with which to study the molecular genesis of normal and pathological
      liver growth. Previously identified carcinogenic genomic changes (such as
      oncogene activation) can be tested for their transforming potency in liver, and
      the contribution to liver growth of genetic changes of unknown significance (such
      as expression of a growth factor) can be directly measured in vivo. Highly novel
      approaches also have become possible because of the liver's unique regenerative
      capacity following injury: introduction of cells from another mouse's liver into
      young AL-uPA mice has resulted in reconstitution of up to 80% of recipient liver
      by donor cells (Rhim et al., 1994). Use of immunotolerant mice and human donor
      cells in this approach should allow creation of mice carrying human livers.
      Finally, by combining transgenic and embryonic stem cell technologies, the latter
      allowing selective mutation or inactivation of desired genes, we now have the
      means to begin to answer many of the critical questions regarding mechanisms of
      liver growth regulation in the intact animal.

PMID- 8532720
TI  - A transgenic mouse model (TG.AC) for skin carcinogenesis: inducible transgene
      expression as a second critical event.
AB  - The v-Ha-ras transgenic TG.AC mouse line behaves as a genetically initiated model
      for mouse skin tumorigenesis with enhanced susceptibility to skin carcinogens.
      TG.AC mice develop epidermal papillomas in fewer than 20 weeks in response to the
      topical application of a variety of chemicals such as complete carcinogens,
      phorbol ester-type tumor promoters, and nonphorbol ester-type tumor promoters as
      well as to full-thickness skin wounds or plucking of the dorsal hair. We have
      found that the pedunculated epidermal papillomas can arise as focal hyperplasias
      from the permanent portion of the follicular epithelium. Expression of the v-Ha
      ras transgene serves as a marker for tumor development since it is expressed at
      significant levels in the papilloma precursors, focal follicular hyperplasias,
      and the papillomas but not in the surrounding skin. Transgene expression
      colocalizes with increased cell proliferation in the papillomas as compared to
      non-tumor bearing surrounding skin. Malignant skin tumors, primarily squamous
      cell carcinomas and sarcomas, develop from sites of papilloma development in
      approximately 40% of papilloma bearing mice. As well as significant levels of
      transgenic v-Ha-ras expression, some of the malignancies also exhibit karyotypic
      changes which include trisomy of chromosome six or fifteen, but not chromosome
      seven. We believe that the TG.AC mouse line serves not only as a model for
      studying the mechanisms of skin tumorigenesis, but will also be a useful adjunct
      to the two year NTP toxicity/carcinogenicity studies by identifying carcinogens
      in fewer than 20 weeks.

PMID- 8532721
TI  - Saccharin-induced bladder cancer in rats.

PMID- 8532722
TI  - Benzoyl peroxide: review of experimental carcinogenesis and human safety data.

PMID- 8532723
TI  - Peroxisome proliferators: potential role of altered hepatocyte growth and
      differentiation in tumor development.
AB  - Continued, exposure-dependent proliferation of hepatocytes in basophilic
      proliferative lesions appears to be critical to the mechanism of peroxisome
      proliferator carcinogenesis in rodents. Identification of the growth regulatory
      pathway(s) involved in the exaggerated hepatocellular proliferation observed in
      these lesions is proceeding. So far, regulatory pathways involving cyclophilin
      and IGFII/M6P receptor have been implicated, while no evidence for involvement of
      HGF-R, TGF alpha, or PPAR is available. Clearly, this work is preliminary and
      additional information is needed. Exposure/dose response relationships for
      hepatocellular proliferation in the basophilic proliferative lesions, as well as
      species differences in regulation of hepatocellular proliferation, will be
      important information for development of realistic assessments of cancer risk in
      humans exposed to peroxisome proliferators. Given the traditional reliance on
      theoretical models of carcinogenesis that assume carcinogen-DNA interaction and
      mutation, utilization of newer information on hepatocellular growth and
      differentiation is expected to significantly change the estimated human risk of
      peroxisome proliferator-induced cancer.

PMID- 8532724
TI  - Considerations concerning the murine hepatocarcinogenicity of selected
      chlorinated hydrocarbons.
AB  - Of the chlorinated hydrocarbons discussed above, all six are associated with
      induction of hepatocellular neoplasia in mice. None of the six is considered to
      be potent mutagen and most are without any significant genotoxic activity as
      assessed by conventional in vitro testing schemes. Although some of the agents
      have biological effects in common (see Figure 4), there is no single biological
      response (mode of action) that they all share to provide a mechanistic basis for
      the observed murine hepatocarcinogenicity. Based upon the information currently
      available for each of the chlorinated hydrocarbons discussed above, it is
      probable that some modes of action may be more contributory to the rodent
      carcinogenic response than others; however, no mode of action, pathway, or
      mechanism should be considered to be mutually exclusive. The murine
      hepatocarcinogenic effect of TriCE is most probably contingent upon its species
      specific metabolism to trichloroacetic acid and DCA. There is fairly consistent
      evidence that cytotoxicity and reparative hyperplasia are associated with doses
      of TriCE that cause induction of liver neoplasms. The possibility that peroxisome
      proliferation is playing a role in the induction of mouse hepatocellular
      neoplasia remains a tempting explanation, since higher intracellular steady
      states of H2O2 production would be consistent with observed enhanced cellular
      proliferation as well as the possibility of in vivo DNA damage. The mouse
      hepatocarcinogenicity associated with TetCE most probably is associated with
      species-specific metabolic production of trichloroacetic acid. As with TriCE,
      cytotoxicity and reparative hyperplasia may represent a potential mode of action
      for the observed hepatocarcinogenicity. Once again, the potential for enhanced
      peroxisome proliferation is consistent with enhanced cell proliferation and
      oxygen radical damage would help explain the random point mutations in ras proto
      oncogenes documented in DNA from TetCE-induced mouse liver tumors. DCA-induced
      mouse hepatocellular neoplasia is probably influenced by cytotoxicity and
      reparative hyperplasia, but there is also recent evidence that DCA may directly
      damage DNA, implying an in vivo genotoxic mechanism may be operational. Likewise,
      altered expression of several genes suggests that subversion of signal
      transduction may play a role in the induction or progression of liver tumor
      development. As with TetCE and TriCE, a role for peroxisome proliferation is
      still a consideration, although the liver tumor response is obvious at doses too
      low to cause peroxisome proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8532725
TI  - Phenobarbital mouse liver tumors: implications of hepatic tumor promotion for
      cancer risk assessment.

PMID- 8532726
TI  - The species specificity of dieldrin- or phenobarbital- induced
      hepatocarcinogenesis: case studies with implications for human health risk
      assessment.

PMID- 8532727
TI  - The use of biological data in addition to the carcinogen bioassay in quantitative
      risk assessment.

PMID- 8532728
TI  - Risk assessment for carcinogenesis promoting agents: need for a weight of all the
      evidence approach.

PMID- 8532729
TI  - Mechanistic considerations in risk assessment for epigenetic tumor-promoting
      carcinogens.

PMID- 8532730
TI  - The potential role of oxidative stress in nongenotoxic carcinogenesis in the
      mouse liver.

PMID- 8532731
TI  - The role of growth factors in mouse skin tumor promotion and premalignant
      progression.

PMID- 8532732
TI  - Hepatic effects of dieldrin and phenobarbital in male B6C3F1 mice and Fisher 344
      rats: species selective induction of DNA synthesis.

PMID- 8532733
TI  - The effect of dieldrin and phenobarbital on preneoplastic hepatic lesion growth
      in male F344 rat and B6C3F1 mouse.

PMID- 8532734
TI  - Modulation of gap junctional intercellular communication by phosphorylation:
      effects of growth factors, kinase activators and phosphatase inhibitors.

PMID- 8532735
TI  - Induction of short-term biomarkers of tumor promotion in skin of CD-1 mice by
      petroleum middle distillates: preliminary observations.
AB  - The induction of sustained epidermal hyperplasia in mouse skin has been shown to
      be a reliable predictor of tumor promoting activity for chemicals as diverse as
      phorbol esters, anthralins, n-dodecane and organic peroxides (DiGiovanni, 1992).
      The results contained herein demonstrate that API 81-07 and API 81-10, petroleum
      middle distillates that exhibit tumor promoting activity in mouse skin, induce
      epidermal hyperplasia and ODC activity. Other petroleum middle distillates
      (odorless light petroleum hydrocarbons, a light vacuum distillate, and a mineral
      seal oil) were also shown to share these activities. It should be emphasized that
      the relevance of these observations to human skin remains unresolved; however,
      the availability of these short-term biomarkers offers the opportunity to address
      the issue by performing comparative investigations on the effects of petroleum
      middle distillates on human skin xenografted to athymic (nude) mice. Such studies
      are being initiated.

PMID- 8532736
TI  - Incorporating the concept of 'invaders' and 'defenders' in the dose-response
      modeling of carcinogens.

PMID- 8532737
TI  - A decision tree approach for carcinogen risk assessment.
AB  - When presented with the information that an environmental chemical produces
      cancer in animals, the default approach is to apply the linearized multistage
      risk model with no mechanistic information. The decision tree presented here
      outlines a straightforward strategy in the collection of information relevant to
      risk assessment. Three situations are noted where a different approach to risk
      assessment should be considered: (1) a tumor response that is not relevant to the
      human situation; (2) chemicals acting through a nongenotoxic/cytotoxic mode of
      action; and (3) chemicals acting through a nongenotoxic/mitogenic mode of action.
      Usually upon learning that a chemical produced a rodent tumor response, no
      additional research is done because of the high costs in money, time, and
      personnel to conduct such studies. Compounding this situation is a widely-held
      view that no amount of mechanistic information will be sufficient to convince
      regulators to depart from the default risk assessment. Hence, there are very few
      data sets to confirm and refine the above suggestions. There should be incentives
      to conduct the research required to obtain the type of information outlined in
      the decision tree approach presented here. All involved with these issues agree
      that the gathering and use of scientific information should be encouraged.
      Hopefully, these suggestions will provide a means of furthering that goal.

PMID- 8532738
TI  - Modulation of gap junctional intercellular communication in rodent, monkey and
      human hepatocyte by nongenotoxic compounds.

PMID- 8532739
TI  - Hypomethylation of DNA: a possible epigenetic mechanism involved in tumor
      promotion.
AB  - The overall objective of our research is to discern mechanisms that can
      facilitate the aberrant expression of oncogenes involved in carcinogenesis. We
      are testing the hypothesis that hypomethylation of DNA is a nongenotoxic
      mechanism underlying the aberrant expression of oncogenes involved in
      carcinogenesis. Hypomethylation may be a mechanism underlying the role of cell
      proliferation in carcinogenesis, and hypomethylation could possibly result from
      an enzymatic replacement of 5-methylcytosine (5MeC) with cytosine that is not
      linked to DNA replication. The testing of this hypothesis can serve as a focal
      point for a mechanism of action-oriented approach for considering key aspects of
      carcinogenesis: aberrant gene expression, heritable epigenetic events, species-to
      species extrapolation/unique species sensitivity, tumor promotion, and
      thresholds. DNA methylation plays a role in the regulation of gene activity.
      There is a persuasive body of evidence indicating that differential methylation
      of DNA (i.e., 5-methylcytosine v. cytosine) is a determinant of chromatin
      structure and that the methyl group provides a chemical signal which is
      recognized by trans-acting factors that regulate transcription. Hypomethylation
      of a gene is necessary but not sufficient for its expression and, therefore, a
      hypomethylated gene can be considered to possess an increased potential for
      expression as compared to a hypermethylated gene. Changes in the methylation
      status of a gene provide a mechanism by which its potential for expression can be
      altered in an epigenetic heritable manner, and it is expected that modifications
      in DNA methylation would result from threshold-exhibiting events. Our
      experimental model is liver tumorigenesis, we focus upon oncogenes (e.g., Ha-ras
      and raf) relevant to mouse liver tumorigenesis, employ the liver tumor prone
      B6C3F1 (C57BL/6 x C3H/He) mouse, and make relevant comparisons with the sensitive
      C3H/He paternal strain and the resistant C57BL/6 maternal strain. A unique aspect
      of this research is that it offers the potential to provide insight regarding
      molecular mechanisms that underlie promotion of carcinogenesis while at the same
      time the results can provide the type of information that is required in order to
      take a more rational approach towards carcinogen risk assessment. Specifically,
      the practical significance of our research is that it addresses the areas of dose
      response relationships, e.g., the existence of threshold-exhibiting mechanisms,
      and species-to-species extrapolation issues. This is discussed within the context
      of the requirement for a rational approach to risk assessment.

PMID- 8532740
TI  - A new optimal wavelength for treatment of port wine stains?
AB  - In this study we investigate light penetration into skin in order to define the
      optimal wavelength for the treatment of port wine stains. A two-layer model
      (epidermis and dermis) is applied with a cylindric tube representing the ectatic
      blood vessel. Light propagation is calculated by the Monte Carlo method. Values
      for the optical properties of the skin were not only taken from the literature,
      but also derived from measurements of the spatially resolved reflectance on the
      human forearm applying a multilayer model. Using the new values, the maximal
      depth of selective vascular injury better fits experimental and clinical
      observations, compared to the values in literature. In addition, the optimal
      wavelength for treatment of port wine stains is shifted to longer wavelengths.

PMID- 8532741
TI  - Elastic properties of human aortas in relation to age and atherosclerosis: a
      structural model.
AB  - A new structural model is described for the tension-radius relationship of blood
      vessels, taking into account their mechanically important constituents: collagen,
      elastin and smooth muscle. The model has four characteristic parameters: EC, the
      Young's modulus of the collagen fibres; ESE, the Young's modulus of the combined
      smooth-muscle/elastin network; epsilon mu, the amount of strain at which the high
      stiffness region on the tension-radius curve is reached, and eta an indicator for
      the degree of collagen fibre stretching. The structural stiffness of the wall
      constituents is reflected by EC and ESE whereas the global stiffness of the
      entire blood vessel is described by epsilon mu and eta. All these elasticity
      parameters are pressure independent, in contrast to generally quoted values for
      the incremental modulus or vascular compliance which are strongly pressure
      dependent. Hence, an objective comparison of the mechanical properties for
      various types of blood vessel, based on the present model parameters, has been
      made possible. The model was successfully fitted to tension-radius data of 65
      human aortas, age range 30-88 years, with moderate or severe atherosclerosis. The
      structural as well as the global stiffness changes with age, e.g. collagen
      stiffness shows a ninefold increase over 60 years. Global stiffness depends on
      atherosclerosis.

PMID- 8532742
TI  - Monte Carlo calculations of epithermal boron neutron capture therapy with heavy
      water.
AB  - Much work over the past decade has centred upon the development of epithermal
      neutron beams for boron neutron capture therapy (BNCT) in an effort to increase
      thermal-neutron flux penetration and dose homogeneity throughout the brain. While
      heavy water has been used extensively to improve neutron penetration associated
      with thermal neutron beams, the effects of heavy water with epithermal neutron
      beams remain largely unexplored. Applying the Monte Carlo code MCNP to a
      heterogenous ellipsoidal skull/brain model, the effects of heavy-water
      replacement are studied for the JRC/ECN Petten HFR epithermal neutron beam.
      Thermal neutron flux and induced gamma depth dose distributions are calculated
      for 20% D2O replacement in comparison to standard brain and skull materials.
      Results are presented for both unilateral and bilateral irradiation. With
      bilateral irradiation, thermal-neutron flux homogeneity is substantially
      increased with 20% D2O replacement, thus improving the potential to give lethal
      doses to boron-10-loaded, disseminated cancer cells whilst avoiding local 'hot
      spots' to healthy tissue. Additionally, the induced gamma dose is reduced by up
      to 30%, substantially lowering the background dose to healthy tissue. With
      bilateral irradiation, 20% D2O replacement increases the therapeutic ratio from
      2.25 to 2.75 for over 4 cm depth centred at the midline of the brain. These
      calculations use documented tumour and blood 10B concentrations for
      boronophenylalanine (BPA) in humans and recently documented neutron relative
      biological effectiveness (RBE) values.

PMID- 8532743
TI  - Effect of radiation rate on electret ionization chambers.
AB  - The dependence of radiation-induced conductivity (RIC) on radiation rate in 254
      microns thick Teflon polyfluoroethylene propylene (FEP) film used in a electret
      ionization chamber (EIC) is discussed and measured with regard to radiation
      dosimetry. Ideally, air-kerma, a quantity linearly related to dose, can be
      determined through measurement of the surface-charge density on the electret
      surface before and after irradiation and observing the difference. However, RIC
      permits trapped surface charge to migrate through the polymer and recombine at
      the collecting electrode which results in a reduced EIC charging efficiency and
      an overestimation of air-kerma in radiation dosimetry. The response of the EIC to
      a given air-kerma is recorded as a function of air-kerma rate. It is predicted
      and observed that surface-charge loss does depend on air-kerma rate. With proper
      adjustment of physical parameters however, a suitably wide range of air-kerma
      rates can be found over which response is flat.

PMID- 8532744
TI  - The effect of scattered radiation in dual-energy analysis.
AB  - Dual-energy techniques can be used to provide additional information during x-ray
      examinations. A recent development has been in the application of dual-energy
      analysis to fluoroscopic procedures. In this paper the effects of scattered
      radiation upon the results obtained with a small area, dual-energy probe used
      during fluoroscopy has been evaluated. The method employed has been the
      development and application of a Monte Carlo photon transport computer program.
      Experimental confirmation of the model has been performed and the model extended
      to study the effects of scattered radiation upon the chemical sensitivity of the
      dual-energy probe. These effects have been studied using a simplified phantom
      geometry to represent a homogeneous patient. The results indicate that for tissue
      analysis where the effective atomic number (Z) is less than 13 the effects of
      scattered radiation lead to errors in estimates of Z of +/- 0.25 when the
      acceptance angle of the detected radiation is below +/- 20 degrees.

PMID- 8532745
TI  - A model for ultrasonic scattering from tissues based on the K distribution.
AB  - A model for the backscattered ultrasound echo from tissues is presented. The
      model takes into account the fact that the range cell being insonified may
      contain only a few scatterers and the number may not be large enough to justify
      the use of a Gaussian model which results in Rayleight statistics for the echo.
      Furthermore, the model also considers the case where the echogenicity of the
      scatterers in the range cell may not be uniform, the lack of uniformity resulting
      from variations in scattering cross-sections produced by the chemical as well as
      biochemical changes brought on by the presence of disease, growth of benign or
      malignant tumours, etc. The model is developed from the fundamental principles of
      scattering using the results available in radar. This new model results in a two
      parameter distribution, namely the K distribution for the echo, thereby making it
      possible to gain information on the number as well as scattering cross-sections
      of the scatterers in the range cell. The model is extended to include the effects
      due to the presence of scatterers having some regular or periodic orientation in
      the range cell, resulting in the so-called generalized K distribution which
      approximates to Rayleight, Rician, or Gaussian under various limiting cases.
      Results of computer simulations and experiments on tissue-mimicking phantoms are
      also provided, which strongly suggest that this new model offers potential for
      tissue characterization.

PMID- 8532746
TI  - Analysis and correction of geometric distortions in 1.5 T magnetic resonance
      images for use in radiotherapy treatment planning.
AB  - The aim of this study is to investigate and correct for machine- and object
      related distortions in magnetic resonance images for use in radiotherapy
      treatment planning. Patients with brain tumours underwent magnetic resonance
      imaging (MRI) in the radiotherapy position with the head fixed by a plastic cast
      in a Perspex localization frame. The imaging experiments were performed on a 1.5
      T whole body MRI scanner with 3 mT m-1 maximum gradient capability. Image
      distortions, caused by static magnetic field inhomogeneity, were studied by
      varying the direction of the read-out gradient. For purposes of accuracy
      assessment, external and internal landmarks were indicated. Tubes attached to the
      cast and in the localization frame served as external landmarks. In the
      midsagittal plane the brain-sinus sphenoidalis interface, the pituitary gland
      sinus sphenoidalis interface, the sphenoid bone and the corpora of the cervical
      vertebra served as internal landmarks. Landmark displacements as observed in the
      reversed read-out gradient experiments were analysed with respect to the
      contributions of machine-related static magnetic field inhomogeneity and
      susceptibility and chemical shift artifacts. The machine-related static magnetic
      field inhomogeneity in the midsagittal plane was determined from measurements on
      a grid phantom. Distortions due to chemical shift effects were estimated for bone
      marrow containing structures such as the sphenoid bone and the corpora of the
      cervical vertebra using the values obtained from the literature. Susceptibility
      induced magnetic field perturbations are caused by the patient and the
      localization frame. Magnetic field perturbations were calculated for a typical
      patient dataset.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532747
TI  - Diffusion in Fe(II/III) radiation dosimetry gels measured by magnetic resonance
      imaging.
AB  - We analyse the diffusion problem in the traditional Fe(II/III) agarose gel system
      employed in MRI studies of radiation dosimetry. The diffusion coefficient is
      measured using an inversion recovery null-point imaging method in a model
      gel/water phantom. The diffusion coefficient of Fe(III) in 1% agarose gel at pH
      1.1 is D = 2.7 +/- 0.3 x 10(-6) cm2 s-1. The diffusion coefficient of Fe(II) is D
      = 3.3 +/- 0.5 x 10(-6) cm2 s-1. Measurement of the diffusion coefficients permits
      simulation of the MRI signal intensity from phantoms with model radiation dose
      distributions. We allow for diffusion of both Fe(II) and Fe(III) in our
      simulations as well as the effect of both relaxation agents on the local spin
      lattice relaxation time T1. We also analyse the effects of the physical penumbra
      on the diffusion problem.

PMID- 8532748
TI  - An analytical approach for compensation of non-uniform attenuation in cardiac
      SPECT imaging.
AB  - Photon attenuation can reduce the diagnostic accuracy of cardiac SPECT imaging.
      Bellini et al have previously derived a mathematically exact method to compensate
      for attenuation in a uniform attenuator. Since the human thorax contains
      structures with differing attenuation properties, non-uniform attenuation
      compensation is required in cardiac SPECT. Given an estimate of the patient
      attenuation map, we show that the Bellini attenuation compensation method can be
      used in cardiac SPECT to provide a quantitatively accurate reconstruction of a
      central region in the image which includes the heart and surrounding soft tissue.
      Simulations using a mathematical cardiac-torso phantom were conducted to evaluate
      the Bellini method and to compare its performance to the ML-EM iterative
      algorithm, and to 180 degrees and 360 degrees filtered backprojection (FBP) with
      no attenuation compensation. 'Bulls-eye' polar maps and circumferential profiles
      showed that both the Bellini method and the ML-EM algorithm provided
      quantitatively accurate reconstructions of the myocardium, with a substantial
      reduction in attenuation-induced artifacts that were observed in the FBP images.
      The computational load required to implement the Bellini method is approximately
      equivalent to that required for one iteration of the ML-EM algorithm, thus it is
      suitable for routine clinical use.

PMID- 8532749
TI  - Application of a surface matching image registration technique to the correlation
      of cardiac studies in positron emission tomography (PET) by transmission images.
AB  - The aim of this work is to assess the accuracy of a surface matching registration
      (SMR) technique for the correlation of cardiac studies in positron emission
      tomography (PET). Registration parameters were estimated by matching
      corresponding body surfaces, extracted from transmission studies, aligned to the
      PET emission images to be correlated. The accuracy of the SMR technique in this
      specific application was assessed by computer simulations, phantom experiments
      and on clinical PET data. Registration accuracy was evaluated in relation to the
      body surfaces (external, internal and the combination of the two) used by the SMR
      method. Better results were found when matching shaped and irregular surfaces
      such as internal lung contours. The robustness of the method was verified for
      different counting statistics recorded in transmission images. A clinical
      validation of the SMR method was performed on fluorine-18-deoxyglucose PET
      cardiac studies.

PMID- 8532750
TI  - Initial assessment of a simple system for frequency domain diffuse optical
      tomography.
AB  - Diffuse optical tomography is an imaging technique whereby spatial maps of
      absorption and scattering coefficients are derived from the characteristics of
      multiply scattered light transmitted through the object. The system described
      here used four intensity-modulated light sources and measurements of the
      intensity and phase (relative to each source) at 16 or 20 detectors on the
      surface of a 10 cm diameter cylinder. An iterative Newton-Raphson algorithm was
      used to estimate the absorption and scattering coefficients at each pixel in a 17
      x 17 array minimizing the difference between measured and calculated values of
      the intensity and phase at the measurement sites. Forward calculations of the
      intensity and phase were based on a multigrid finite-difference solution of the
      frequency domain diffusion equation. Numerical simulations were used to examine
      the resolution, contrast, and accuracy of the reconstructions as well as the
      effects of measurement noise, systematic uncertainties in source-detector
      location, and accuracy of the initial estimates for the optical properties.
      Experimental tests also confirmed that the system could identify and locate both
      scattering and absorbing inhomogeneities in a tissue-simulating phantom.

PMID- 8532751
TI  - Comments on the article 'Radiance and particle fluence'.

PMID- 8532752
TI  - Problems associated with the use of broad-band illumination sources for
      photodynamic therapy.

PMID- 8532753
TI  - Comments on the article 'A model for calculating tumour control probability in
      radiotherapy including the effects of inhomogeneous distributions of dose and
      clonogenic cell density'.

PMID- 8532754
TI  - The influence of membrane permeability for ions on cell behaviour in an electric
      alternating field.
AB  - The behaviour of a cell in an electric alternating field has been investigated,
      taking into account the field-induced diffusion flows of ions through the
      membrane. We computed the difference in ion concentration between the internal
      and external sides of the membrane and the transmembrane diffusion potential
      induced by the external field. We also studied the effects of these flows on
      dielectric properties of a tissue in the radio frequency range. The value of the
      electric permittivity at low frequencies decreases gradually with the increase of
      membrane permeability for ions, while the electric permittivity at high
      frequencies is unchanged. These effects are especially important for analysis of
      the dielectric spectrum of a tissue or cell suspension which has undergone the
      influence of various physical or chemical agents, e.g. ionizing radiation or
      detergents.

PMID- 8532755
TI  - Limitations of a pencil beam approach to photon dose calculations in lung tissue.
AB  - A common limitation in treatment planning systems for photon dose calculation is
      to ignore the impact on electron transport and photon scatter from patient
      heterogeneities. The heterogeneity correlation is often based on scaling
      operations along beam rays as for the method according to Batho or the more novel
      approach of 1D convolutions along beam paths applied in pencil-beam-based
      systems. The effects of the limitation have been studied in a mediastinum
      geometry for a wide range of beam qualities by comparing the results from a
      pencil-beam-based treatment planning system with the results from Monte Carlo
      calculations. As expected, the deviations within unit-density volumes are small
      while deviations in low-density volumes increase with increasing beam energy from
      approximately 3% for 4 MV to 14% for 18 MV x-rays as a result of increased
      electron disequilibrium.

PMID- 8532756
TI  - Radiotherapy treatment planning with dynamic wedges--an algorithm for generating
      wedge factors and beam data.
AB  - If the jaws of a linear accelerator are moved under computer control during
      irradiation, dose distributions similar to those with wedge filters can be
      produced. Varian linear accelerators utilize this effect to give a 'dynamic
      wedge', using segmented treatment tables (STTs). An algorithm is described to
      generate the dose per monitor unit at any point in a beam, using the STT values.
      Dynamically wedged beams are modelled as the superposition of static asymmetric
      beams, using an algorithm based on beam data measured for symmetric beams.
      Predictions of wedge factors, depth doses and profiles generated using the
      algorithm are compared with measurements. Good agreement is found between
      predictions and measurements. The calculation time is typically 5 ms/dose point
      on a PC with a 486DX processor.

PMID- 8532757
TI  - Intensity-modulated arc therapy with dynamic multileaf collimation: an
      alternative to tomotherapy.
AB  - The desire to improve local tumour control and cure more cancer patients, coupled
      with advances in computer technology and linear accelerator design, has spurred
      the developments of three-dimensional conformal radiotherapy techniques.
      Optimized treatment plans, aiming to deliver high dose to the target while
      minimizing dose to the surrounding tissues, can be delivered with multiple fields
      each with spatially modulated beam intensities or with multiple-slice treatments.
      This paper introduces a new method, intensity-modulated arc therapy (IMAT), for
      delivering optimized treatment plans to improve the therapeutic ratio. It
      utilizes continuous gantry motion as in conventional arc therapy. Unlike
      conventional arc therapy, the field shape, which is conformed with the multileaf
      collimator, changes during gantry rotation. Arbitrary two-dimensional beam
      intensify distributions at different beam angles are delivered with multiple
      superimposing arcs. A system capable of delivering the IMAT has been implemented.
      An example is given that illustrates the feasibility of this new method.
      Advantages of this new technique over tomotherapy and other slice-based delivery
      schemes are also discussed.

PMID- 8532758
TI  - A theoretical study of the thermal response of skin to cryogen spray cooling and
      pulsed laser irradiation: implications for treatment of port wine stain
      birthmarks.
AB  - The successful treatment of port wine stain (PWS) patients undergoing laser
      therapy is based on selective thermal coagulation of blood vessels without
      damaging the normal overlying epidermis. Cryogen spray cooling of skin may offer
      an effective method for minimizing epidermal thermal injury. Inasmuch as the
      density of melanosomes and depth of PWS blood vessels can vary considerably, an
      optimum cooling strategy is required on an individual patient basis. We present a
      theoretical study of the thermal response of various pigmented PWS lesions to
      spray cooling in conjunction with flashlamp-pumped pulsed dye laser irradiation
      (585 nm). Results of our model indicate that precooling of skin using
      tetrafluoroethane as the cryogen spray is sufficient to eliminate epidermal
      thermal injury when using incident fluences less than 10 J cm-2 and 8 J cm-2 on
      patients with intermediate and high epidermal melanin content, respectively.
      Cryogens that have lower boiling points than tetrafluoroethane may allow
      successful treatment when using fluences equal to or greater than those
      indicated.

PMID- 8532759
TI  - A method for calculating the dose due to capture gamma rays in accelerator mazes.
AB  - An empirical technique for calculation of the capture gamma ray dose in the maze
      of high-energy medical accelerators is described. The total photon dose was
      measured along the maze centre line and by use of a graphical technique the
      capture gamma dose and the low-energy photon dose component were determined.
      Tenth-value lengths for both photon dose components are reported for four medical
      accelerators operating with megavoltages in the range 16.8-22.0 MV. The capture
      gamma dose and the low-energy photon dose in the maze were related to the
      following parameters: the room surface area, the distance from the isocentre to
      the inner maze entrance, and the neutron head leakage at a fixed distance from
      the target.

PMID- 8532760
TI  - K x-ray fluorescence measurements of bone lead concentration: the analysis of low
      level data.
AB  - K line x-ray fluorescence (KXRF) measurements of bone lead have emerged as a
      promising new biological marker of internal lead dose in epidemiological studies.
      Some disagreements exist, however, over the analysis of data at low levels of
      bone lead concentration. In this study, we performed 30 serial measurements on
      each of three phantoms containing spiked amounts of lead. Chemical analysis of
      these phantoms using an inductively coupled plasma mass spectrometer (ICPMS)
      indicated that the lead concentrations were 0.30, 5.77, and 11.57 micrograms g-1.
      Analysis of the data was performed using several definitions of a minimum
      detectable limit (MDL) to recode data below the MDL, and using all of the
      continuous point estimates of lead concentration in the phantom (including
      negative estimates). The results demonstrate that the use of MDLs to recode low
      level observations reduces the efficiency of the analysis and the ability to
      distinguish between the phantoms. Retaining all point estimates of KXRF-measured
      bone lead concentration provides less bias and greater efficiency in comparing
      the mean or median levels of bone lead of different populations.

PMID- 8532761
TI  - Quantitative x-ray diffraction analysis of bone and marrow volumes in excised
      femoral head samples.
AB  - The aim of this paper is to apply the technique of quantitative x-ray diffraction
      analysis (QXDA) to trabecular bone tissue to demonstrate that quantitative data
      of the ratio of bone and marrow volumes within the trabecular region can be
      obtained. Apparatus has been constructed for measuring energy dispersive x-ray
      diffraction spectra of human femoral head samples in the diagnostic x-ray energy
      range. Individual diffraction peaks due to bone and marrow tissue were identified
      in the measured spectra. The relative intensities of the two peaks within the
      spectra quantify the relative proportions of the two components, and so the bone
      to marrow peak ratio is proposed as a parameter which is capable of providing
      information on the osteoporotic state of trabecular tissue. Preliminary results
      indicate a significant correlation between this method and the bone density
      measurement techniques of quantitative computed tomography and Compton scatter
      densitometry. Results have shown that the use of a synthetically prepared
      calibration curve can enable absolute measurement of bone or marrow volumes.

PMID- 8532762
TI  - A comparative study of three fast algorithms to estimate cerebral blood flow and
      distribution volume using N-isopropyl-p-[123I]iodoamphetamine and two SPECT
      scans.
AB  - To estimate regional cerebral blood flow (rCBF) and distribution volume (Vd)
      using N-isopropyl-p-[123]iodoamphetamine (IMP) and two SPECT data (early and
      delayed data) measured at two discrete time points, three fast algorithms are
      implemented, which are the table look-up method (TLU), the linear least-squares
      fitting method (LLSF), and the linear search method (LS). A two-compartment model
      was used as the IMP kinetic model. These algorithms were applied to the early and
      delayed data measured by the two scan protocols, t1 = 12 min, t2 = 54 min (scan
      A) and t1 = 12 min, t2 = 85 min (scan B). The estimated rCBF and Vd values using
      the present three algorithms were in good agreement with those using the
      nonlinear least-squares fitting technique and dynamic SPECT data. The
      quantitative value and signal to noise (S/N) ratio of rCBF images by TLU was not
      changed whether scan A or scan B was used. However, the S/N of the Vd image by
      TLU using scan B improved over that using scan A. The same tendency was observed
      in the results of LLSF and LS. The CPU times for the parametric imaging of CBF
      and Vd images for one slice (64 x 64 matrix) were 0.04, 0.09, and 0.14 s using
      TLU, LLSF, and LS, respectively. In conclusion, the present three algorithms gave
      reasonably accurate estimates of rCBF and Vd using two SPECT data, and are well
      suited for parametric imaging because of their good statistical properties and
      high computational efficiency.

PMID- 8532763
TI  - Filtered backprojection reconstruction of combined parallel beam and cone beam
      SPECT data.
AB  - The reconstruction problem for a combined parallel beam (PB) and cone beam (CB)
      imaging geometry has been addressed. The general algorithm (CB-FBP) of Defrise
      and Clack has been applied to this geometry and shown to provide accurate images
      as expected. A second algorithm specifically tailored to the PB-CB geometry was
      developed. It uses the general principles of the CB-FBP method to combine a shift
      variant filtering of the PB data with a standard reconstruction of the CB data
      using the algorithm of Feldkamp, Davis and Kress (FDK). This 'mixed' algorithm
      has the advantage of fewer interpolation steps, thereby reducing reconstruction
      time and providing more accurate reconstructions. The algorithms were applied to
      noiseless data from a computer-generated 3D Shepp phantom. Both the CB-FBP
      algorithm and the mixed algorithm successfully combine the CB and the PB data to
      correct the well known artefacts observed when reconstructing CB data acquired
      with a circular orbit. The mixed algorithm is about twice as fast as CB-FBP and
      results in better image quality, due to decreased discretization errors. However,
      the two algorithms yield comparable image quality when applied to a disc phantom
      measured with a two-headed SPECT system.

PMID- 8532764
TI  - Statistical basis for the determination of optical pathlength in tissue.
AB  - In this paper we show how to derive the mean and variance of the transilluminated
      signal obtained in models of light propagation in tissue, based both on a
      stochastic Monte Carlo method and on a deterministic diffusion approximation. The
      theoretical treatment of the Monte Carlo model applies only to integrated
      intensity measurements, whereas the diffusion approximation gives an estimator
      for the time-dependent case as well. We present results that show the accurate
      prediction of Monte Carlo statistics, and propose that the diffusion
      approximation is therefore a suitable mechanism for incorporating noise into
      modelling procedures.

PMID- 8532765
TI  - Identification of IGF-I in the calvarial suture of young rats: histochemical
      analysis of the cranial sagittal sutures in a hyperthyroid rat model.
AB  - Premature closure of cranial sutures has been known as one of the complications
      of juvenile or congenital hyperthyroidism. Thyroid hormone is an anabolic agent
      for bone formation in the early stages of childhood development. In children,
      excess thyroid hormone acts as an acceleration factor for the skeletal bone,
      whereas in adult hyperthyroidism, it causes bone mineral loss due to the high
      turnover rate of bone formation and consequently bone resorption. In addition,
      there are numerous literature descriptions concerning the interactions among bone
      metabolism, hormones, and growth factors, among which insulin-like growth factor
      I (IGF-I) is the most abundantly found growth factor in osteoblasts and in bone
      models in vivo. We therefore investigated whether or not the cranial sutures show
      accelerated closure and how the local growth factors or cytokines participate and
      function in local bone metabolism after administration of exogenous excess
      thyroid hormone in a rat model. A total of 60 female Wistar rats, aged 10 days,
      were divided into two groups, the triiodothyronine (T3)-treated group (n = 30, T3
      0.1 microgram/gm of body weight per day) and the control group (n = 30, saline
      vehicle only), and were maintained and subsequently sacrificed at 15, 30, and 60
      days. The parameters of cranial width derived from the morphologic measurements
      of the skull indicated that the lambda-asterion distance at 30 days and the
      pterion-bregma distance at 60 days in the T3-treated group were significantly
      decreased compared with those of the control group. Furthermore, the fluorescent
      histologic findings showed fluorescent labeling with no interruption along the
      suture edges, suggesting continuous bone formation, and displayed narrowing of
      the suture gap of the sagittal suture in the T3-treated group. Tartrate resistant
      acid phosphatase staining showed very little osteoclastic activity in the
      sagittal suture, especially in the T3-treated group. The intensity of
      immunohistochemical staining of IGF-I was markedly increased in the suture
      margins of the T3-treated group. There were no significant differences observed
      either in the skull base measurements or in the histologic and histochemical
      findings of the skull base or the coronal suture between the groups. More
      significantly, excess administration of thyroid hormone enhanced the cranial
      sagittal suture closure; therefore, it was proposed that local IGF-I plays an
      important role in sagittal sutural bone formation.

PMID- 8532766
TI  - Diagnosis of silicone gel breast implant rupture by ultrasonography.
AB  - To prospectively evaluate the efficacy of ultrasonography in the diagnosis of
      ruptured silicone gel breast implants, 98 patients (192 implants) underwent
      preoperative breast ultrasonography prior to silicone gel breast implant removal.
      The prevalence of implant rupture confirmed at surgery in this group of patients
      was 62 of the 192 implants (32 percent). Of the 60 implants diagnosed as ruptured
      by ultrasonography, 46 were confirmed as having visible defects at surgery (true
      positive) for a positive predictive value of 77 percent. Of the 132 implants
      diagnosed as intact by ultrasonography, 116 were confirmed as intact at surgery
      (true negative) for a negative predictive value of 88 percent. Overall, the
      sensitivity of ultrasonography for implant rupture was 74 percent, and the
      specificity was 89 percent. These findings demonstrate that ultrasonography is an
      effective imaging modality for the diagnosis of silicone gel breast implant
      rupture. Compared with mammography, ultrasonography appears to offer superior
      sensitivity and specificity without radiation exposure or discomfort. Although
      magnetic resonance imaging has shown considerable promise in the diagnosis of
      implant rupture, ultrasonography provides comparable sensitivity at a fraction of
      MRI's cost.

PMID- 8532767
TI  - Response of locoregional and systemic symptoms to breast implant replacement with
      autologous tissues: experience in 37 consecutive patients.
AB  - This paper addresses the effectiveness of implant removal as treatment for
      systemic symptoms perceived to be related to breast implants. We reviewed our
      experience with 37 consecutive patients who underwent autologous tissue
      replacement of reconstructive breast implants. All patients were motivated
      primarily by concern regarding systemic symptoms for which diagnoses could not be
      provided. The majority of treated patients also had locoregional complaints and
      physical findings suggestive of either implant failure or symptomatic contracture
      and/or inflammatory disease. Essentially all patients with locoregional symptoms
      experienced improvement or resolution of these throughout the period of follow-up
      (6 to 27 months). However, relief from systemic complaints proved short-lived,
      with a 90 percent early response rate falling to 32 percent by 6 months
      postoperatively. We continue to strongly counsel patients to pursue reoperation
      only when locoregional symptoms are persistent and associated with physical or
      radiographic findings of significant contracture or implant failure. We conclude
      that although explantation with or without autogenous reconstruction may be
      appropriate in certain circumstances, it should not be proposed as a treatment
      for systemic rheumatologic or neurologic complaints.

PMID- 8532768
TI  - Topical putrescine (Fibrostat) in treatment of hypertrophic scars: phase II
      study.
AB  - Previous studies indicated that tissue transglutaminase plays a role in the cross
      linking of type III procollagen in wound matrices and that this may be inhibited
      by 50 mM putrescine in vitro. For this reason, the clinical effect of 50 mM
      putrescine in a eutectic vehicle (Fibrostat) was studied in this phase II double
      blind crossover study in 43 patients. Twenty of the patients had had recent
      surgery and were studied for product safety rather than efficacy. No toxic
      effects were observed in this group of patients, and only 1 of the 23 unoperated
      patients had a rash during treatment. The observed effect of Fibrostat versus
      sham treatment of 1 month's duration in active hypertrophic scar was a
      significant improvement of hypertrophy in 23 patients during the Fibrostat
      treatment arm, regardless of the order in which treatment was received. It is
      suggested that Fibrostat is a safe therapeutic agent for treatment of
      hypertrophic scar. Clinical examples to illustrate its use are given.

PMID- 8532769
TI  - Surgical treatment of postburn boutonniere deformity.
AB  - A new method of surgical treatment of postburn boutonniere deformity was used in
      124 fingers of 66 patients. This method includes reconstruction of the lateral
      band's position of an extensor apparatus and anatomic continuity of a central
      band. Before tendon plasty, passive movements in a proximal interphalangeal joint
      are restored and contracture of others joints is released. If the soft tissue of
      the digital back is affected, tendon grafts are covered with a groin pedicled
      flap. With this method we could restore active movements in the proximal
      interphalangeal joint in 89.2 percent of the patients and avoid fusion or
      amputation. The failures were connected with serious intrajoint changes.

PMID- 8532770
TI  - The effects of temporalis muscle manipulation on skull growth: an experimental
      study.
AB  - Craniofacial reconstructive procedures are frequently associated with some
      dissection or transposition of the temporalis muscle. During active growth, such
      muscle manipulations may influence craniofacial development. The purpose of this
      study was to determine the effects of surgical manipulation of the temporalis
      muscle on craniofacial skeletal growth and morphology. Twenty-five New Zealand
      White rabbits underwent temporalis muscle surgery at 6 weeks of age. Group I (n =
      6) underwent a sham procedure and served as a control group. Group II (n = 6)
      underwent simple elevation of the left temporalis muscle and immediate
      reapproximation. Group III (n = 7) underwent complete transection of the left
      temporalis muscle. Group IV (n = 6) underwent elevation of the left temporalis
      muscle and transposition to the left zygoma. Growth alterations were evaluated by
      standardized cephalometric x-rays. Baseline anteroposterior skull x-rays were
      performed preoperatively and every 3 weeks for the duration of the study. The
      study was terminated at 24 weeks of age. At this point, dry skull preparations
      were analyzed quantitatively by direct cephalometric evaluation. Manipulations of
      the temporalis muscle produce changes in local skull morphology and affect
      craniofacial growth. Skull length increases when the action of the temporalis
      muscle is interrupted either transiently or permanently, while skull width
      decreases. Temporalis muscle transposition to the orbit resulted in altered
      orbital dimensions. Qualitative analysis of local skull morphology further
      revealed posterior displacement of the external auditory meatus, a depressed
      temporalis fossa, and multiple resorption cavities following elevation of the
      temporalis muscle.

PMID- 8532771
TI  - A new surgical technique for postaxial polydactyly of the foot.
AB  - A new technique for the treatment of the most common type of postaxial
      polysyndactyly of the foot is presented. The technique employs four local flaps
      and a skin graft from the pedal area. The outermost skeletal elements and nail
      tissue were excised, while the fourth interdigital commissure was deepened. This
      differs from historical techniques of desyndactylization in the hand that have
      been applied to surgery in the foot. The new technique is characterized by
      minimal waste of tissue from the outermost toe with preservation of the dominant
      fifth toe.

PMID- 8532772
TI  - Rejection of the component tissues of limb allografts in rats immunosuppressed
      with FK-506 and cyclosporine.
AB  - One-hundred and fourteen limb transplantations have been performed across a major
      histoincompatibility barrier between donor ACI (RT1a) and recipient Lewis (RT1l)
      rats immunosuppressed with various dosages of FK-506 and cyclosporine. Three
      hundred and thirty biopsy specimens from 64 animals have been evaluated
      histologically for signs of rejection. A new histologic grading system is
      introduced to classify the process of rejection in the component tissues (skin,
      muscle, bone, and articular cartilage) of a limb allograft. The results indicate
      that FK-506 is a more potent immunosuppressive agent than cyclosporine in
      preventing the rejection of the skin component of a limb transplant. With twice
      weekly intermittent immunosuppression with FK-506, the rejection of muscle, bone,
      and cartilage can be prevented for an indefinite time, although all long-term
      surviving animals died at around 300 days, probably of graft-versus-host disease.
      Based on the histologic stages of rejection in the different tissues at the same
      point in time, it is evident that each component tissue of a limb transplant
      rejects over a different time period. This probably reflects a hierarchy of
      antigenicity, with skin being most antigenic, muscle being intermediate in
      antigenicity, and bone and cartilage being least antigenic. Although this grading
      system is not the ultimate solution, it may allow a more objective comparison of
      experimental limb transplantation in the future.

PMID- 8532773
TI  - Reduction in peripheral nerve allograft antigenicity with warm and cold
      temperature preservation.
AB  - Lymphocyte migration into fresh and preserved peripheral nerve allografts was
      assessed to determine the effects of preservation time, preservation temperature,
      and graft harvest technique on the immunologic response to the peripheral nerve
      allograft. Peroneal nerve was harvested from either live or cadaveric (tissue)
      donors and stored as 1.5-cm segments at 5 degrees C or 37 degrees C for 1, 3, 5,
      or 7 days. Each of nine outbred ewes then received multiple segments of peroneal
      autograft, fresh allograft, and preserved nerve allograft implants. Lymphocyte
      migration was studied 7 days after implantation by intravenous injection of
      autologous 111In-labeled lymphocytes and quantified by gamma counter. Lymphocyte
      migration into fresh allografts (7212 +/- 1575) increased an average of 4.1 times
      over fresh autograft tissue (1758 +/- 421; p < 0.05). Short-term preservation (24
      hours) at both temperatures enhanced lymphocyte migration into pretreated
      allograft tissue (12684 +/- 2575 at 5 degrees C, 8751 +/- 1577 at 37 degrees C)
      as compared with fresh allograft (7212 +/- 1575). Conversely, 7 days of
      pretreatment at both 5 degrees C (3586 +/- 1421) and 37 degrees C (1570 +/- 414)
      resulted in migration values not significantly different from autograft. No
      statistically significant difference was seen between grafts harvested from live
      (5710 +/- 1651) versus cadaveric (tissue) donors (4013 +/- 832) after 5 days of
      cold preservation.

PMID- 8532774
TI  - Metaidoioplasty: an alternative phalloplasty technique in transsexuals.
AB  - The various techniques for phalloplasty in female-to-male transsexuals produce
      results that are more or less acceptable, both aesthetically and functionally.
      However, all these techniques will lead to extensive scarring of the donor area.
      Metaidoioplasty uses the clitoris, overdeveloped by hormonal treatment, to
      construct a microphallus in a way comparable to the correction of chordae and
      lengthening of urethra in male pseudohermaphrodites and in cases of severe
      hypospadias. It will not leave any scars outside the genital area. My experience
      in 32 female-to-male transsexuals is presented. At best, metaidoioplasty will
      provide a small phallus hardly, if at all, capable of sexual penetration. Still,
      I consider it to be a method of choice in cases where the clitoris seems large
      enough to provide a phallus that will satisfy the patient.

PMID- 8532775
TI  - De novo cartilage generation using calcium alginate-chondrocyte constructs.
AB  - These studies investigated the utility of calcium alginate as a biocompatible
      polymer matrix within which large numbers of chondrocytes could be held
      successfully in a three-dimensional structure and implanted. Further, the ability
      of chondrocyte-calcium alginate constructs to engraft and generate new cartilage
      was examined. Chondrocytes isolated from calf shoulders were mixed with a 1.5%
      sodium alginate solution to generate cell suspensions with densities of 0, 1.0,
      5.0, and 10.0 x 10(6) chondrocytes/ml. The cell suspensions were gelled to create
      disks that were placed in subcutaneous pockets on the dorsums of nude mice. The
      alginate concentration and CaCl2 concentration used to make the disks also were
      varied. A total of 20 mice were implanted with 67 bovine chondrocyte-calcium
      alginate constructs. Samples with an initial cellular density of at least 5.0 x
      10(6) chondrocytes/ml demonstrated gross cartilage formation 12 weeks after
      implantation. Cartilage formation was observed microscopically in specimens with
      a cellular density as low as 1.0 x 10(6) chondrocytes/ml. The histoarchitecture
      of the new cartilage closely resembled that of native cartilage. Cartilage
      formation was independent of CaCl2 concentration (15 to 100 mM) or alginate
      concentration (0.5% to 4.0%) used in gel polymerization.

PMID- 8532776
TI  - On being 50.

PMID- 8532777
TI  - Ethics in surgical practice.

PMID- 8532778
TI  - Free fibula flap mandible reconstruction for oral obstruction secondary to giant
      fibrous dysplasia.
AB  - Fibrous dysplasia is a disorder of bone that may be associated with
      endocrinopathies and skin pigmentation. The pathologic, proliferative expansion
      and distortion of the skeleton is of unknown etiology. Craniofacial involvement
      that includes the mandible can exhibit gigantic disproportions and dysfunction.
      Treatment has evolved to include more aggressive strategies of resection and
      sophisticated reconstructive techniques. The reported case is noteworthy for the
      unrelenting growth of craniofacial fibrous dysplasia in an adult female with
      endocrinopathies, progressing to oral obstruction that required urgent treatment
      utilizing immediate free bone-flap reconstruction. The free fibula flap was
      employed to restore mandibular continuity after palliative subtotal
      mandibulectomy. Bony healing to dysplastic tissue occurred in the remaining
      mandibular segment. This case illustrates that fibrous dysplasia has the capacity
      for virulent regrowth subsequent to conservative resection. Defects following
      radical surgery for giant fibrous dysplasia of the mandible can be reconstructed
      with a microsurgical bone-flap technique.

PMID- 8532779
TI  - Modifications of the paraspinous muscle flap: anatomy and clinical application.
AB  - Soft-tissue defects of the back, particularly involving the paravertebral
      tissues, are generally covered with myocutaneous, muscle, or fasciocutaneous
      flaps. The case of a 64-year-old man with a paravertebral malignant fibrous
      histiocytoma is reported. To ensure adequately radical margins, the ipsilateral
      trapezius and latissimus dorsi muscles as well as the costal periosteum and the
      spinous processes were resected between T9 and T12. The resulting defect was
      covered with a pedicled latissimus dorsi flap and an island flap of the
      paravertebral muscles. Prompted by this case, we studied the blood supply of the
      paravertebral muscles in 10 cadavers. The vasculature was visualized after
      flushing with colored latex and microsurgical dissection. Another 4 specimens
      were subjected to angiography and tomography. In the majority of cases (8 of 10),
      three perforators emerging from the intercostal arteries were identified. These
      were found to communicate in a longitudinal and vertical direction. Before
      piercing the fascia, they ramified in three layers matching the layers of the
      paravertebral muscles. Since the intercostal arteries were shown to communicate
      through anastomoses of adequate caliber, the paravertebral muscles appear to be
      useful candidates for proximally or distally pedicled transposition or island
      flaps.

PMID- 8532780
TI  - Minimally invasive harvesting of rectus abdominis myofascial flap in the cadaver
      and porcine models.
AB  - The rectus abdominis muscle has been used in reconstructive surgery as a
      superiorly and an inferiorly based pedicle flap as well as free flap. Since flap
      necrosis is unusual, the primary morbidity of the harvesting is donor-site
      complications, including infections, seromas, poor cosmesis, and hernias.
      Minimally invasive surgery has been used in abdominal, thoracic, and urologic
      surgeries with favorable results. To date, flap harvesting and other soft-tissue
      surgeries have been considered inaccessible to minimally invasive surgery based
      on existing techniques. We demonstrate in the (5) cadaver and (5) porcine models
      the technique of endoscopic harvesting of a superiorly based vertical myofascial
      pedicle flap. Without insufflation, we create a soft-tissue space to operate
      within using external skin traction. We demonstrate that this flap harvesting can
      be performed without the obligatory large skin incision. Donor-site complications
      may be decreased with less tissue disruption. In our cadaver models, we have
      tried using the rectus without the anterior fascia based on its superior pedicle
      for breast reconstruction. For this purpose, we use the endoscissors with cautery
      to create a tunnel up on the chest wall. The muscle based on its superior pedicle
      could be rotated up on the chest wall subcutaneously, allowing primary closure of
      the anterior sheath using the endostapler. If the anterior sheath is sacrificed
      or cannot be closed primarily, mesh can be used to create a reinforcing layer
      stapled to the edges of fascia and midline. Endoscopic surgery offers an
      excellent alternative for soft-tissue reconstruction without compromising the
      results.

PMID- 8532781
TI  - Concept of triangular, trapezoidal, and rectangular debulking of eyelid tissues:
      application in Asian blepharoplasty.
AB  - There has been continued refinement and understanding in the concepts of Asian
      blepharoplasty. Among Asians, aesthetic upper eyelid surgery to convert a
      creaseless upper eyelid (popularly referred to as "single eyelid") to one with a
      crease ("double eyelid") is the most frequently performed cosmetic surgery in
      Asia and among Asians living in the Western hemisphere. I have discussed my
      understanding of the concept of this surgery, utilizing a tarsal height-based
      external incision method plus assymmetrical debulking of the preaponeurotic
      tissues, including some fat, septum orbitale, pretarsal and preseptal orbicularis
      oculi muscles, and preseptal skin.

PMID- 8532782
TI  - Excision of neck redundancy with single Z-plasty closure.
AB  - In selected patients, particularly males, redundancy of skin of the neck can be
      treated effectively by direct excision and a single large Z-plasty closure so
      that the horizontal portion corresponds to the neck crease. Reduction of the
      thyroid cartilage can be performed simultaneously. The relative advantages and
      disadvantages between this approach and the more commonly performed facelift are
      discussed.

PMID- 8532783
TI  - Introduction of a modified Krukenberg operation.
AB  - A modified Krukenberg operation was used in 25 patients to reconstruct their limb
      function. We modified the operation as follows: (1) only pronator teres and
      supinator are preserved as motor muscles, (2) the flexor carpi ulnaris is
      included in the ulnar ray flap and the brachioradialis in the radial ray flap,
      and (3) the length of the forearm trunk is kept 12 to 15 cm. Having undergone
      strict postoperative training, 22 of 25 patients got excellent or good results.

PMID- 8532784
TI  - Umbilicoplasty: the construction of a new umbilicus and correction of umbilical
      stenosis without external scars.

PMID- 8532785
TI  - Surgically significant nutritional supplements.
AB  - This is not an exhaustive study of all nutritional supplements that patients may
      be taking. The most frequently used and those potentially most detrimental or
      most beneficial for surgical patients have been chosen for review of pertinent
      effects. It is essential to ask patients specifically about supplements or
      unusual dietary habits that may affect their surgical outcome prior to their
      invasive procedure and to keep in mind the supplements that may improve their
      outcome.

PMID- 8532786
TI  - Modification of Mustarde technique for correction of epicanthus in Asian
      patients.

PMID- 8532787
TI  - Hook of the hamate fracture without direct trauma.

PMID- 8532788
TI  - The tension nose.

PMID- 8532789
TI  - Isolated congenital unilateral alar defect: a rare anomaly.

PMID- 8532790
TI  - Routine use of loupe magnification for microvascular anastomoses: at what price?

PMID- 8532791
TI  - Silicone breakdown and capsular synovial metaplasia in textured-wall saline
      breast implants.

PMID- 8532792
TI  - History of the discovery of the reversal of blood flow through arteries and
      veins.

PMID- 8532793
TI  - Vascular anatomy of the galeal occipitalis flap: a cadaver study.
AB  - The vascular anatomy of the galeal occipitalis flap was studied in 10 fresh
      cadavers by an intraarterial dye injection technique. The scalp flap was based
      posteriorly, incorporating both the occipital and posterior auricular arteries. A
      good transmidline anastomosis was demonstrated between the two occipital arteries
      in the full-thickness scalp flap. However, in the isolated galeal flap, although
      the axial distribution of the occipital artery was maintained, fewer transmidline
      connections were seen between the two occipital arteries. The posterior auricular
      artery was consistently visualized in all dissections, and it showed good
      connections with the ipsilateral occipital artery. However, there were very few
      anastomoses between the two posterior auricular arteries across the midline. The
      rich anastomotic network between the occipital artery and the posterior auricular
      artery extended well beyond the vertex. This study showed that a large flap can
      be raised if both the occipital artery and the posterior auricular artery are
      included in its base. The occipital artery is a vessel of satisfactory size and
      is potentially a good vascular source for a thin galeal free flap. It is
      recommended that the flap be raised at the subperiosteal level for ease of
      dissection and protection of the vessels, which are initially in the subgaleal
      plane and then arborize in the galea.

PMID- 8532794
TI  - Gore-Tex nasal augmentation.

PMID- 8532795
TI  - Carpal tunnel release.

PMID- 8532796
TI  - A system for accessing our valuable human resources.

PMID- 8532798
TI  - Double cannula and tubing, single SAL machine at 1 atm of negative suction
      pressure.

PMID- 8532797
TI  - Errors in compounding acid chemical peel solutions.

PMID- 8532799
TI  - Hazard of inferior pedicle breast reduction concurrent with explanation of old
      subglandular implants.

PMID- 8532800
TI  - On breast reduction.

PMID- 8532801
TI  - Histologic study of the skin with gold thread implantation.

PMID- 8532802
TI  - Notes on the history of the adoption of liposuction.

PMID- 8532803
TI  - The external shaving technique in aesthetic rhinoplasty.
AB  - External shaving is an accepted technique in the treatment of rhinophyma. The
      application of external shaving to aesthetic rhinoplasty is also valuable in the
      treatment of a thick, sebaceous nasal tip that does not respond to standard
      reduction rhinoplasty. External shaving will reduce the thickness of the nasal
      tip skin and enhance tip definition. Fifty consecutive patients undergoing
      external shaving were followed over a 5-year period. The majority of the cases
      were secondary rhinoplasties. The results reveal a very high success rate, with
      one significant complication, a hypertrophic scar, and two minor complications.
      Proper diagnosis, patient selection, and surgical technique produce predictable
      and favorable aesthetic results.

PMID- 8532804
TI  - The back-and-forth septoplasty.
AB  - This paper describes a new technique of septoplasty especially devised to
      minimize and simplify surgery and to preserve at the same time the integrity of
      mucosa at the critical area of articulation between the caudal quadrangular
      cartilage and the vomeropremaxillary crest. Two special instruments specifically
      designed for this type of operation are illustrated. The technique finds a
      specific clinical application to cosmetic surgery of the nose when a functional
      problem exists.

PMID- 8532805
TI  - Classification of facial rejuvenation techniques based on the subperiosteal
      approach and ancillary procedures.
AB  - Subperiosteal face lift is a new way of doing facial rejuvenation. There are
      multiple variations of technique described by several authors. Each variable
      introduced to the technique may be relevant to the final outcome and potential
      safety or complications. The most important variables are extent of dissection,
      combination of the subperiosteal dissection with other planes of dissection,
      suspension methods, and use of ancillary techniques. A systematic classification
      of techniques in which a lesser or greater subperiosteal dissection is made has
      been devised. Each technique is individualized and differentiated from seemingly
      alike techniques. A list of ancillary techniques is included. This classification
      is useful for facial evaluation and preoperative planning. A surgical proposal is
      made individualizing each patient's facial aesthetics rather than giving one type
      of operation to every patient. This classification is also useful for comparison
      and analysis of surgical results obtained with different techniques. It has the
      versatility of adding new variations and any ancillary technique adapted to the
      surgeon's idiosyncrasy. It can be used as a model to develop a classification of
      traditional face lift techniques.

PMID- 8532806
TI  - The submental artery flap: an anatomic study.
AB  - Coverage of facial defects is frequently challenging. Despite the numerous flaps
      described, the search for additional flaps with good color match and minimal
      donor-site morbidity continues. We present a flap based on the submental vessels.
      The anatomy based on 24 fresh cadaver dissections injected with Microfil is
      outlined. The submental artery is a branch of the facial artery after it exits
      from the submandibular gland. It runs over the mylohyoid and below the mandible.
      It continues either superficial or deep to the anterior belly of the digastric
      muscle. It supplies the skin of almost the entire triangle of the neck and a
      variable area across the midline. The facial artery diameter is 2.0 to 2.8 mm,
      and that of the submental artery is 1.0 to 1.5 mm. The facial vein provides
      venous drainage. From the anatomic study, the submental artery flap appears to
      have a long vascular pedicle and should be useful in facial and intraoral
      reconstructions. The size of the pedicle also makes it attractive as a free
      tissue transfer. We feel that this flap has great clinical potential.

PMID- 8532807
TI  - The latissimus dorsi added fat flap for natural tissue breast reconstruction:
      report of 15 cases.
AB  - The latissimus dorsi added fat flap is an alternative method of natural tissue
      breast reconstruction. A significant volume of additional subcutaneous back fat
      is left attached to a traditional latissimus dorsi flap, avoiding the need for an
      additional implant. The surgical technique and results in 15 patients are
      discussed.

PMID- 8532808
TI  - The cephalic vein: an aid in free TRAM flap breast reconstruction. Report of 12
      cases.
AB  - The harvesting of the cephalic vein is a simple and effective technique for
      providing or augmenting venous drainage in free TRAM flap breast reconstruction.
      It may be divided distally and rotated about the infraclavicular fossa as a
      cephalic vein transfer or used as a source of free vein grafts. It is easily
      harvested with minimal morbidity. Its anatomy, surgical technique, indications,
      and results of use are discussed. In some circumstances, a cephalic vein transfer
      may allow greater areas of the free TRAM flap to be used more safely. This is
      discussed.

PMID- 8532809
TI  - Superiority of the microvascularly augmented flap: analysis of 50 transverse
      rectus abdominis myocutaneous flaps for breast reconstruction.
AB  - Our experience with 50 transverse rectus abdominis myocutaneous (TRAM) flap
      transfers was evaluated as to the types of TRAM flaps, indications for breast
      reconstruction with a TRAM flap, and complications. The TRAM flap was transferred
      as a free flap in 7 patients, a unipedicled flap in 14 patients, and a
      microvascularly augmented flap in 29 patients. Microvascular augmentation was
      performed through the contralateral inferior epigastric vascular system to the
      superiorly pedicled muscle in 10 patients who had undergone radical mastectomy
      and the ipsilateral inferior epigastric vascular system in 19 patients who had
      undergone modified radical mastectomy. In this series, the incidence of flap-site
      complications, including total flap loss, partial flap loss, and fat necrosis,
      was lowest in the microvascularly augmented flap group. Particularly, incidence
      of partial flap loss in the microvascularly augmented flap group was
      significantly lower than in the unipedicled flap group (p < 0.01). These outcomes
      demonstrated the superiority of the microvascularly augmented TRAM flap for
      breast reconstruction.

PMID- 8532810
TI  - The effect of cigarette smoking on the survival of free vascularized and pedicled
      epigastric flaps in the rat.
AB  - Microsurgeons suspect that cigarette smoking reduces the survival of free
      vascularized flaps and replantations, but this has never been proven. This
      experimental study investigates the effect of smoking on free-flap survival. A
      fasciocutaneous epigastric flap was used in 30 rats as a free flap and in 30 rats
      as a pedicled flap. Of each group, 10 rats were smoked 6 weeks before and 2 weeks
      after surgery, 10 rats were smoked only 6 weeks before surgery, and 10 rats
      underwent the sham smoking procedure. Also, a distally based dorsal skin flap was
      cut in all rats, representing a random vascularized flap. Vitality and size of
      both flaps and patency of the vascular anastomoses were assessed 14 days after
      surgery. The epigastric flaps were monitored by laser Doppler flowmetry and
      thermometry during the experiment. Survival of the free vascularized epigastric
      flaps was significantly lower in smoking rats. All pedicled flaps except one
      survived. The epigastric flaps only necrosed or survived completely, exactly
      correlating to the patency of the vascular anastomoses. The mean surviving area
      of the dorsal flaps was best for nonsmoking rats, worse for only preoperatively
      smoking rats, and worst for preoperatively and postoperatively smoking rats. The
      differences were statistically significant. Postoperative laser Doppler flow
      differed significantly between surviving and dying flaps, affirming the value of
      laser Doppler flow monitoring in microvascular surgery. In conclusion, this study
      proves that smoking of cigarettes is detrimental to the survival of free
      vascularized flaps.

PMID- 8532811
TI  - External oblique myocutaneous flap coverage of large chest-wall defects following
      resection of breast tumors.
AB  - Defects resulting from resection of advanced breast tumors can be quite large,
      posing a difficult reconstructive challenge. A significant number of such
      patients present with local recurrences after receiving external beam radiation
      and/or chemotherapy treatments. Pectoralis major, latissimus dorsi, rectus
      abdominis, and omental flaps with split-thickness skin grafts have been
      recommended for closure of chest-wall defects. What is often excluded from the
      list of reconstructive options is the external oblique myocutaneous flap. In our
      series of 20 consecutive patients treated at Memorial Sloan-Kettering Cancer
      Center, an external oblique myocutaneous flap was used to cover these large chest
      wall defects successfully. The median age of our patient population was 54.5
      years, and 68 percent of them presented with local recurrence. Fifty percent had
      external beam radiation, and fifty percent had received chemotherapy. Twenty-five
      percent of our study group had had both treatments. The mean chest-wall defect
      measured 326 cm2, corresponding to a 20 x 16 cm area. We believe that the
      external oblique myocutaneous flap should be considered a safe and reliable
      option when reconstruction of large chest-wall defects is contemplated.

PMID- 8532812
TI  - [Differential diagnosis and diagnostic markers of Alzheimer's disease].

PMID- 8532813
TI  - [Psychoneuroimmunology: brain-immunity related medicine].

PMID- 8532814
TI  - [Therapy of emotional disturbance by manipulation of the biological clocks].

PMID- 8532815
TI  - [Modern family and adolescence].

PMID- 8532816
TI  - [Fragile X syndrome and mental disorders].

PMID- 8532817
TI  - [Effects of desipramine and clomipramine on alpha 2-adrenergic receptor function
      in nucleus accumbens: studies with intracerebral dialysis in freely moving rats].
AB  - The effect of alpha 2-adrenoceptor agonist, clonidine (CLN) (100 micrograms/kg,
      i.p.), on the noradrenalin metabolite 3-methoxy-4-hydroxyphenylethyleneglycol
      (MHPG)-total in the rat nucleus accumbens after desipramine (DMI) (20 mg/kg,
      i.p.) and clomipramine (CMI) (20 mg/kg, i.p.) treatment was estimated in the
      freely moving rat by intracerebral dialysis. Locomotor activity was measured
      simultaneously by the Animex. Locomotor activity in the control decreased after
      CLN administration, in accordance with the decrease in MHPG. The difference of
      locomotor activity and MHPG between the single dose trial with DMI, CMI and the
      control did not reach statistical significance throughout the experiment. The
      results suggest that a single injection of DMI and CMI have not an inhibitory
      effect on presynaptic alpha 2-adrenergic receptor in the nucleus accumbens. Next,
      DMI (20 mg/kg, i.p.) and CMI (20 mg/kg, i.p.) were injected once daily for 14
      days and experiments, the same method as used on the single dose trial. A
      difference in locomotor activity and MHPG between the chronic DMI treatment and
      the control reached statistical significance. A significant reduction of
      locomotor activity was found during the 60 min period of the experiment. In
      addition, a significant reduction of MHPG was found during the 30-90 min period.
      A difference in locomotor activity and MHPG between the chronic CMI treatment and
      the control reached statistical significance. A significant reduction of
      locomotor activity was found during the 60 min period of the experiment. In
      addition, a significant reduction of MHPG was found during the 30-120 min period.
      The results suggest that the chronic DMI treatment and the chronic CMI treatment
      may diminish the CLN-induced reduction of MHPG via the subsensitivity of
      presynaptic alpha 2-adrenergic receptor in the nucleus accumbens.

PMID- 8532818
TI  - [A psychopathological study of hypochondriacal symptoms in manic-depressive
      psychosis].
AB  - Depressive patients often have some hypochondriacal symptoms, but their various
      patterns are prone to be overlooked. The author presents statistical
      characteristics of 24 depressive patients (based on DSM-III-R, major depression,
      melancholic type), who have some hypochondriacal symptoms. Taking into
      consideration these statistical characteristics and a detailed analysis of
      representative cases, the author proposes a psychopathological perspective and
      classification of patients, who have hypochondriacal symptoms during manic
      depressive psychosis. The author presents five characteristics, namely, (1) age
      during depression, (2) personality trait, (3) anxiety-agitation, (4) dependency,
      and (5) guilt feelings, as factors that raise the hypochondriacal symptoms in
      depressive patients. Based on such characteristics, depressive patients with
      hypochondriacal symptoms can be classified into 3 subgroups; the anxiety
      agitation group, the dependency group and the guilt feeling group. Among the
      anxiety-agitation group hypochondriacal depression is considered as a mixed state
      of manic-depressive psychosis with the grandiosity of hypochondriacal idea and
      agitation as manic expressions. In personal relations, patients in the anxiety
      agitation group are ego-centric ("eigenwelt-bezogen"). On the contrary, patients
      in the dependency group are often conscious of others, and their hypochondriacal
      symptoms mean an escape from reality and also the intention of a new personal
      relationship. In the guilt feeling group, hypochondriacal symptoms arise due to
      guilt obsessiveness. A difference in the 3 groups also appears in the discourse
      characteristics of the hypochondriacal symptoms. The discourse of patients in the
      anxiety-agitation group can be called a "Circle type" or "Go-round type", since
      their complaints are various, but have a common structure. Discourse in guilt
      feeling group can be characterized as a "Tied-up type" or "Standstill type",
      since they repeat only a fixed complaint in a depressive state. Discourse in
      dependency group does not have a regular linguistic structure, and the patients
      make a great deal of importance in complaining to others. In addition to such
      considerations, the author suggests an affinity between hypochondriacal symptoms
      and manic elements on the grounds that some patients have hypochondriacal
      symptoms in their manic state, and that depressive patients with hypochondriacal
      symptoms, especially in the anxiety-agitation group, as well as manic patients,
      are strongly concerned with the present. Treatment for hypochondriacal depression
      requires the therapist to recognize the individuality of the disease, to
      safeguard against suicide and other ramifications.

PMID- 8532819
TI  - Gender differences in behaviour: activating effects of cross-sex hormones.
AB  - The relative contribution of organizing and activating effects of sex hormones to
      the establishment of gender differences in behaviour is still unclear. In a group
      of 35 female-to-male transsexuals and a group of 15 male-to-female transsexuals a
      large battery of tests on aggression, sexual motivation and cognitive functioning
      was administered twice: shortly before and three months after the start of cross
      sex hormone treatment. The administration of androgens to females was clearly
      associated with an increase in aggression proneness, sexual arousability and
      spatial ability performance. In contrast, it had a deteriorating effect on verbal
      fluency tasks. The effects of cross-sex hormones were just as pronounced in the
      male-to-female group upon androgen deprivation: anger and aggression proneness,
      sexual arousability and spatial ability decreased, whereas verbal fluency
      improved. This study offers evidence that cross-sex hormones directly and quickly
      affect gender specific behaviours. If sex-specific organising effects of sex
      hormones do exist in the human, they do not prevent these effects of androgen
      administration to females and androgen deprivation of males to become manifest.

PMID- 8532821
TI  - Menstrual synchrony: agenda for future research.
AB  - While many studies have confirmed McClintock's (1971) finding of human menstrual
      synchrony, it is also clear that menstrual synchrony does not always occur. To
      better understand the mechanisms and functions of this phenomenon, this paper
      suggests directions for future research aimed at delineating the context and
      conditions under which menstrual synchrony occurs. It is proposed that the
      following research issues be explored: multiple sources of social influence;
      quality of social relationships; analyzing couple (or group) data; who
      synchronizes to whom?; group size; putative pheromones; age and age diversity;
      and contraceptive practices.

PMID- 8532820
TI  - Multihormonal responses to apomorphine in mental illness.
AB  - The neuroendocrine responses to subcutaneous (SC) administration of the dopamine
      (DA) agonist apomorphine (APO) hydrochloride (0.75 mg) were studied in a large
      group of subjects: 110 drug-free inpatients with either DSM-III-R schizophrenia
      (SCZ, n = 46), schizoaffective disorder (SAD, n = 14), or major depressive
      episode (MDE, n = 50), plus 18 hospitalized controls. Compared to a saline test,
      APO induced a significant increase of growth hormone (GH), adrenocorticotropin
      (ACTH), and cortisol (COR) release and a decrease in prolactin (PRL) secretion.
      No change in thyrotropin (TSH) levels was observed. In the total sample the
      extents of ACTH, COR and GH responses were correlated, but in the group of 88
      subjects who exhibit a normal GH stimulation this correlation disappeared. This
      discrepancy suggests that APO-induced ACTH and COR stimulation may be mediated by
      pathways different from those mediating GH stimulation. According to diagnostical
      categories, we found significant lower ACTH and COR stimulation in the
      schizophrenic group and in patients with SAD, compared with that among controls
      or depressed patients. We found also a significant difference between subgroups
      of schizophrenic patients. These results agree with the hypothesis that different
      aspects of psychosis might involve different subtypes of DA-receptors with
      different localizations and sensitivities.

PMID- 8532822
TI  - Anxiolytic-like effects of selective mineralocorticoid and glucocorticoid
      antagonists on fear-enhanced behavior in the elevated plus-maze.
AB  - The effects of intracerebroventricular (ICV) administration of the
      mineralocorticoid receptor (MR) antagonist, RU28318, and the glucocorticoid
      receptor (GR) antagonist, RU38486, were studied on behavior of rats exposed to a
      compartment previously associated with a stressor, and placed subsequently in an
      elevated plus-maze test. Fear-motivated immobility behavior was attenuated by the
      MR antagonist in a dose of 50 or 100 ng ICV, whereas the GR antagonist alone or
      simultaneous administration of both antagonists had no significant effect. In the
      elevated plus-maze, immediately after the exposure to the conditioned stressor,
      both the GR antagonist (50 ng) and MR antagonist (50 ng) increased the percentage
      of time the rats spent on open arms, and increased the amount of entries into
      these open arms. These data are interpretated in terms of the involvement of the
      GR and MR in fear and anxiety.

PMID- 8532823
TI  - Thyroid axis function during the menstrual cycle in women with premenstrual
      syndrome.
AB  - Fifteen women with premenstrual syndrome (PMS) and 15 control women were tested
      twice for thyroid axis measures, once during the follicular and once during the
      luteal phase of the menstrual cycle. While PMS and control women did not differ
      in mean hormone values during either phase of the menstrual cycle, PMS women
      showed significantly greater variability in hormone measures including TSH, T3
      uptake, T4, and FTI relative to controls. These findings are consistent with the
      conceptualization that, for a subset of women with PMS, thyroid axis
      abnormalities may contribute to their disorder. Additionally, when analyzed in
      the sample as a whole, the menstrual cycle exerted a significant effect on
      reverse T3 with greater levels observed in the luteal relative to the follicular
      phase of the cycle.

PMID- 8532824
TI  - Heterosexual activity: relationship with ovarian function.
AB  - Previous research demonstrated a relationship between the temporal pattern of
      heterosexual activity and an index of ovarian functioning. In the current study,
      this relationship was investigated in 147 menstruating heterosexual women (aged
      19-53). They kept prospective daily records of menses, basal body temperature,
      sexual activity, and other behaviors for three consecutive menstrual cycles. In
      contrast to previous findings, women with intermediate levels of sexual activity
      displayed more frequent optimal menstrual cycles. Pheromones, semen absorption,
      and orgasm-related changes were tested as mediators for a causal influence of
      sexual activity on ovarian functioning; none was supported. Exploratory analyses
      tested the hypothesis that anovulatory cycles (with presumably lower
      progesterone) would display more sexual activity than ovulatory cycles. This
      hypothesis was supported, and the difference in sexual activity was limited to
      the second half of the cycle, after ovulation would have occurred. Thus, the
      findings incorporate temporal precedence of ovulation to support the idea that
      physiological processes influence the level of sexual activity in heterosexual
      women.

PMID- 8532825
TI  - Behavioural activation produced by CRH but not alpha-helical CRH (CRH-receptor
      antagonist) when microinfused into the central nucleus of the amygdala under
      stress-free conditions.
AB  - The central nucleus of the amygdala (CeA) is known to be involved in the
      regulation of autonomic, neuroendocrine, and behavioural responses in stress
      situations. The CeA contains large numbers of corticotropin-releasing hormone
      (CRH)-containing cell bodies and terminals. In the present study we examined (by
      continuous behaviour observations) the effects of a high dose of CRH (150 ng) and
      two doses of the CRH-receptor antagonist (alpha-hCRH: 1.0 and 0.1 micrograms)
      after microinfusion into the CeA in freely moving male Wistar rats under stress
      free conditions. In comparison with control, alpha-hCRH infusion did not cause
      any behavioural activation. In contrast CRH-infusion revealed a long-lasting
      increase in grooming and exploration with a concomitant decrease in behaviours
      specified as resting. These results indicate that the CRH system in the CeA does
      not seem to be activated in stress-free conditions, but its activation is of
      importance for active behavioural responses.

PMID- 8532826
TI  - Hormonal responses to dl-fenfluramine challenge are not blunted in seasonal
      affective disorder.
AB  - Prolactin and cortisol responses to acute challenge with dl-fenfluramine (60 mg
      PO) were examined in 10 (6 women and 4 men) patients with seasonal affective
      disorder (SAD) and the same number of age, gender, menstrual status, and season
      matched healthy controls. Neither prolactin nor cortisol response was different
      in SAD patients in comparison to controls. The reasons for discrepancy in
      findings between studies are discussed.

PMID- 8532827
TI  - Effects of early prenatal dexamethasone on the cognitive and behavioral
      development of young children: results of a pilot study.
AB  - The effect of early prenatal dexamethasone (DEX) exposure on cognitive and
      behavioral development, behavior problems, and temperament were examined in 26
      consecutively identified children aged 6 mo to 5 1/2 years, whose mothers had
      been DEX-treated during pregnancy because their offspring was at risk for
      congenital adrenal hyperplasia (CAH), and compared with 14 children from
      untreated CAH-risk pregnancies. Three children in each group were CAH-affected.
      Assessments were performed by way of mother-completed standard questionnaires. No
      significant differences in cognitive abilities or behavior problems were
      identified. On temperament questionnaires, DEX-exposed children showed more
      Shyness (p < .004), greater Emotionality (p < .03), less Sociability (p < .04),
      and a trend for greater Avoiddance (p < .07) than unexposed children. DEX-exposed
      children also had significantly higher Internalizing (p < .002) and Total Problem
      scores (p < .05) on the behavior problem measure for 2-3 year olds. The results
      should be considered preliminary until they have been replicated by the study of
      a larger sample and direct examination of the children.

PMID- 8532828
TI  - Some material for a campaign in support of radiation sciences.

PMID- 8532829
TI  - Determination of the rate constant for the reaction of hydroxyl and oxide
      radicals with cysteine in aqueous solution.
AB  - The techniques of pulse radiolysis and absorption spectroscopy have been used to
      determine absolute rate constants for the reaction of hydroxyl and oxide radicals
      with cysteine (CysS) species in aqueous solution. Using measured equilibrium
      constants for radical disulfide anion formation, over the pH range 6.0-13.0,
      observed reaction rate constants were resolved into their constituent reactions
      .OH + CysSH-->H2O + CysS. and .O(-) + CysS-( + H2O)-->CysS. + 2OH- with
      calculated limiting rate constants of (5.35 +/- 0.82) x 10(9) and (3.28 +/- 0.49)
      x 10(8) dm3 mol-1 s-1, respectively. The rate constant for hydroxyl radical
      reaction with CysS- was found to be the same as that for CysSH.

PMID- 8532830
TI  - The stress response--a radiation study section workshop.

PMID- 8532831
TI  - The presence of DNA breaks and the formation of chromatid aberrations after
      incorporation of 125IdUrd may be necessary but are not sufficient to block cell
      cycle progression in G2 phase.
AB  - Cell progression into mitosis and chromatid aberration frequencies were compared
      in two Chinese hamster ovary (CHO) cell lines after incorporation of 125IdUrd.
      Asynchronous, exponentially growing populations of CHO K1 and the DNA repair
      deficient, radiation-sensitive CHO irs-20 cells were compared after a 10-min
      exposure to 14.8 kBq/ml 125IdUrd. Essentially no differences were seen for either
      end point between the cells of the two cell lines. As the cells in S phase at the
      time of labeling entered the mitotic cell selection window, the number of mitotic
      cells of each cell line declined to approximately 60% of the respective unlabeled
      control. Chromosome analysis of the mitotically selected cells indicated an 125I
      decay-dependent increase in the number of chromatid aberrations in cells of both
      cell lines. The appearance of aberrations together with the known rates of
      production and rejoining of DNA double-strand breaks show that cells are able to
      progress through G2 phase and into mitosis in the presence of such breaks. The
      data suggest that DNA damage may be necessary, but is not sufficient to cause a
      radiation-induced blockade of cell progression through G2 phase.

PMID- 8532832
TI  - Rejoining of gamma-radiation-induced single-strand breaks in plasmid DNA by human
      cell extracts: dependence on the concentration of the hydroxyl radical scavenger,
      Tris.
AB  - The rejoining of single-strand breaks induced by gamma irradiation in plasmid DNA
      under different scavenging conditions is described using human cell extracts. As
      the scavenging capacity of the irradiated solution increases from 1.5 x 10(7) to
      3 x 10(8) s-1 using Tris-HCl as a scavenger, the ratio of single- to double
      strand breaks is reduced from approximately 70:1 to 40:1. After irradiation, a
      proportion of DNA molecules have no initial strand breaks but contain damage that
      is converted to strand breaks when incubated either at 37 degrees C or in the
      presence of cellular extract. Repair of damage by the extracts is dependent upon
      the scavenging capacity of the irradiated solution. Optimal rejoining is observed
      when the scavenging capacity is < 1.5 x 10(7) s-1, and results in the repair of
      some initial strand breaks. As the scavenging capacity increases to 3 x 10(8) s-1
      the proportion of breaks repaired is significantly reduced. The relative increase
      in the yield of double-strand breaks and reduced repairability of single-strand
      breaks at a scavenging capacity of 3 x 10(8) s-1 is consistent with the concept
      that the severity of damage increases upon increasing the scavenger
      concentration.

PMID- 8532833
TI  - Chromosomal radiosensitivity in G2-phase lymphocytes as an indicator of cancer
      predisposition.
AB  - Sanford et al. (Int. J. Radiat. Biol. 55, 963-981, 1989) have reported that G2
      phase cells from many heritable cancer-prone conditions exhibit higher yields of
      X-ray-induced chromosome damage than those found in the majority of healthy
      controls. We have applied their protocol to lymphocytes of a group of control and
      cancer-prone individuals to see if we could confirm these observations. For
      control donors we observed higher aberration yields, different kinetics and more
      interexperiment variability than found by Sanford et al. These differences could
      not be attributed to unavoidable minor variations in procedures (e.g. serum
      batches, glassware washing methods), but the difference in X-ray qualities used
      in the two laboratories may have made a small contribution to the discrepancies.
      We attribute some of our experimental variability to the fact that, to varying
      extents in different experiments, centrifugation of cells prior to irradiation
      can slow down the progression of cells into metaphase and that cells can continue
      to repair during the harvesting procedure (centrifugation and hypotonic
      treatment). We have applied the assay to cases of ataxia telangiectasia (AT,
      homozygotes and heterozygotes), xeroderma pigmentosum (homozygotes and
      heterozygotes), familial adenomatous polyposis and the syndromes Li-Fraumeni,
      basal cell nevus, Down's and Fanconi's but have been unable to discriminate
      between these groups and controls except for AT homozygotes. By including a
      control sample in parallel with samples from cancer-prone groups we found a
      significant difference in mean aberration yields between controls and AT
      homozygotes and heterozygotes, but not for the other groups. Since technical
      features could explain the discrepancies between our laboratories, we have
      devised our own G2-phase assay which appears to be giving promising results.

PMID- 8532834
TI  - Characterization of multilocus lesions in human cells exposed to X radiation and
      radon.
AB  - Human TK6 lymphoblasts were exposed to X radiation or radon, and thymidine kinase
      negative (TK-/-) mutants were selected, isolated and harvested for analysis of
      structural changes in the TK gene. A large majority (82%) of the radon-induced
      mutants, 74% of the X-radiation-induced mutants and 45% of the spontaneous
      mutants lost the entire active TK allele. To analyze these mutants further we
      measured the loss of heterozygosity at several loci neighboring the TK locus on
      chromosome 17q. A greater proportion (61%) of the radon-induced mutants than X
      radiation-induced or spontaneous mutants harbored the smaller lesions involving
      the TK allele alone or extending from the TK locus to one or both of the closest
      neighboring sequences tested. Further, 21% of the X-radiation-induced mutants but
      only 5% of the radon-induced mutants lost heterozygosity at the col1A1 locus, 31
      Mb from the TK gene. These results are in agreement with a recent analysis of
      radon- and X-radiation-induced lesions inactivating the HPRT gene of TK6 cells,
      in which we reported that a lower percentage of radon- than X-radiation-induced
      mutants showed lesions extending to markers 800 kb or more from the HPRT gene on
      the X chromosome (Bao et al., Mutat. Res. 326, 1-13, 1995). In the present study,
      we observed that the percentage of slowly growing and very slowly growing TK-/-
      mutants was greater after treatment with radon than after treatment with X
      radiation, regardless of the type of lesion present. It is possible, therefore,
      that the radon-induced lesions are complex and/or less easily repaired, leading
      to slow growth in a large proportion of the surviving mutant cells.

PMID- 8532835
TI  - Induction and repair of chromosome aberrations in scid cells measured by
      premature chromosome condensation.
AB  - Severe combined immunodeficient (scid) murine cells, which are defective in both
      repair of DNA double-strand breaks and V(D)J recombination, are deficient in DNA
      dependent protein kinase (DNA-PK), a protein which forms an activated complex
      with the DNA end-binding Ku proteins (p80 and p70) upon association with damaged
      DNA. Xrs 5 cells are deficient in the Ku p80 protein and also fail to form an
      active DNA-PK repair complex. Since both scid and xrs cells are defective in the
      same protein complex, we compared the kinetics of chromosome repair in scid cells
      to results published previously for xrs 5 cells. C.B-17 cells, scid cells and
      scid cells complemented with a single human chromosome 8 were irradiated with 6
      Gy and allowed to repair from 0-24 h before fusion to HeLa cells for chromosome
      condensation. Breaks and dicentrics were visualized by fluorescence in situ
      hybridization. All cells had the same initial amount of chromosome damage, but
      scid cells had a slower rate of rejoining, more unrejoined breaks and more
      dicentrics than C.B-17 and scid cells with human chromosome 8. The scid cells
      appear to respond differently than xrs 5 cells, despite both cells lacking an
      essential component of the same DNA repair complex.

PMID- 8532836
TI  - Use of a three-color chromosome in situ suppression technique for the detection
      of past radiation exposure.
AB  - A three-color chromosome in situ suppression technique and classical cytogenetic
      analysis were compared for the detection of chromosomal aberrations in blood
      lymphocytes of 27 patients who had undergone radiation therapies from 1 month to
      9 years ago. Depending on the respective regimens of therapy, a high variability
      was found in the aberration data. Aberration rates depended on the interval
      between exposure and scoring rather than on the locally applied radiation doses,
      which were rather uniform among most patients. Chromosome in situ suppression was
      found to be superior to classical cytogenetics with respect not only to the
      spectrum of detectable aberrations but also to the uncovering of long-term
      effects of irradiation. Of particular interest were the relative stability of the
      frequency of radiation-induced reciprocal translocations and the utility of
      chromosome in situ suppression to uncover complex rearrangements.

PMID- 8532837
TI  - Biological dosimetry by interphase chromosome painting.
AB  - Both fluorescence in situ hybridization of metaphase spreads with whole
      chromosome probes and premature chromosome condensation in interphase nuclei have
      been used in the past to estimate the radiation dose to lymphocytes. We combined
      these techniques to evaluate the feasibility of using painted interphase
      chromosomes for biodosimetry. Human peripheral lymphocytes were exposed to gamma
      rays and fused to mitotic Chinese hamster cells either immediately after
      irradiation or after 8 h incubation at 37 degrees C. Interphase or metaphase
      human chromosomes were hybridized with a composite probe specific for human
      chromosomes 3 and 4. The dose-response curve for fragment induction immediately
      after irradiation was linear; these results reflected breakage frequency in the
      total genome in terms of DNA content per chromosome. At 8 h after irradiation,
      the dose-response curve for chromosome interchanges, the prevalent aberration in
      interphase chromosomes, was linear-quadratic and similar to that observed for
      metaphase chromosomes. These results suggest that painting prematurely condensed
      chromosomes can be useful for biological dosimetry when blood samples are
      available shortly after the exposure, or when interphase cells are to be scored
      instead of mitotic cells.

PMID- 8532839
TI  - Measurements of radiobiological effectiveness in the 85 MeV proton beam produced
      at the cyclotron CYCLONE of Louvain-la-Neuve, Belgium.
AB  - The RBE of the 85 MeV proton beam produced at the cyclotron of Louvain-la-Neuve
      using 60Co gamma rays as the reference radiation was determined for survival of
      Chinese hamster ovary cells in vitro and for intestinal crypt regeneration in
      mice in vivo. Cell survival curves determined at different depths yielded, for a
      surviving fraction (SF) of 0.01, RBE values of 1.11 +/- 0.05 at the initial
      plateau of the unmodulated beam, 1.10 +/- 0.03 at the middle of a 0.5-cm spread
      out Bragg peak (SOBP), 1.03 +/- 0.03 at the beginning of a 3-cm SOBP and 1.07 +/-
      0.03 at the end of a 3-cm SOBP. The highest RBE values were obtained at the
      middle of the 0.5-cm SOBP and at the end of the 3-cm SOBP (RBE = 1.22 and 1.16,
      respectively, at SF = 0.5), although the variations are not statistically
      significant. Irradiations with 3-Gy fractions separated by an interval of 3.5 h
      yielded RBEs of 1.11 +/- 0.30 and 0.90 +/- 0.32 at the initial plateau and at the
      middle of the 0.5-cm SOBP, respectively. Irradiations of mice at the middle of
      the 3-cm SOBP yielded an RBE of 1.08 +/- 0.03 for 20 regenerated crypts at a
      proton dose of 12.3 Gy.

PMID- 8532838
TI  - Lack of evidence for an association between the frequency of mutants or
      translocations in circulating lymphocytes and exposure to radon gas in the home.
AB  - Radon measurements in the living room and main bedroom of 41 houses in the town
      of Street, Somerset, England have been made. Exposure levels, weighted using the
      formula of the UK National Radiological Protection Board, of 19-484 Bq m-3 (about
      half > 100 Bq m-3) were found. Blood samples were obtained from a total of 66
      occupants in these homes, and the frequency of genetic alterations in lymphocytes
      was estimated using two different end points. Gene mutations at the hypoxanthine
      guanine phosphoribosyl transferase locus were determined in T lymphocytes for 65
      subjects using a clonal assay, and the frequency of the BCL-2 t(14;18)
      translocation, a chromosomal event associated with leukemia/lymphoma, was
      estimated in lymphocytes using a polymerase chain reaction-based technique for 64
      subjects. In neither case was a significant correlation with radon levels in the
      home found, in contrast to our earlier observation with a smaller series.

PMID- 8532840
TI  - Characterization of X-ray-induced immunostaining of proliferating cell nuclear
      antigen in human diploid fibroblasts.
AB  - The repair of X-ray-induced DNA damage related to the proliferating cell nuclear
      antigen (PCNA) was characterized in human diploid fibroblasts by an indirect
      immunofluorescence method. PCNA staining induced by X rays was lost after DNase I
      treatment but not after RNase treatment. The staining was not induced when ATP
      was depleted or the temperature was lowered to 0 degrees C during the X
      irradiation. When cells were incubated at 37 degrees C after X irradiation, PCNA
      staining diminished gradually and was almost entirely absent 12-15 h later. On
      the other hand, PCNA staining persisted during aphidicolin treatment even 20 h
      after X irradiation. Induction of PCNA staining was not affected by the
      aphidicolin treatment. Cycloheximide treatment did not affect induction of the
      staining either, but did inhibit the disappearance of the staining. There was no
      difference in the staining pattern and time course of PCNA staining after X
      irradiation between normal and xeroderma pigmentosum group A (XP-A) cells. These
      results imply that PCNA-dependent, aphidicolin-sensitive DNA polymerases may be
      involved in repair of X-ray-induced DNA damage in vivo, but the repair initiation
      step could be different from that of nucleotide excision repair initiated by XP
      proteins.

PMID- 8532841
TI  - Radiation-induced autophosphorylation of epidermal growth factor receptor in
      human malignant mammary and squamous epithelial cells.
AB  - In an effort to identify events initiating up-regulation of epidermal growth
      factor receptor after single and repeated radiation exposures, we investigated
      the role of epidermal growth factor receptor, a receptor protein tyrosine kinase,
      in radiation-induced signal transduction. Human malignant mammary, MCF-7, and
      squamous, A431, cells showed low baseline phospho-tyrosine levels of epidermal
      growth factor receptor, permitting reproducible dose-dependent stimulation of
      epidermal growth factor receptor autophosphorylation after exposure to epidermal
      growth factor. MCF-7 cells exhibited a mean 2.3-fold increase (95% confidence
      interval: 1.91, 2.65; P < 0.0001) in levels of epidermal growth factor
      phosphorylation in response to exposures of 2 Gy, which was substantially less
      than the epidermal growth factor receptor Y phosphorylation induced by epidermal
      growth factor. A quantitatively similar radiation response was seen in A431
      cells. In the dose range of 1 to 4 Gy, no clear dose response was seen. There was
      a rapid induction of radiation-induced epidermal growth factor receptor Y
      phosphorylation, starting within 2 min, with maximum values between 0.5 and 5 min
      after radiation exposure followed by a slower decline to baseline levels after 20
      min. The data presented identify the epidermal growth factor receptor protein
      tyrosine kinase associated with the plasma membrane as one target for ionizing
      radiation in the dose range used in radiotherapy.

PMID- 8532842
TI  - Thyroid cancer after diagnostic administration of iodine-131.
AB  - To provide quantitative data on the risk of thyroid cancer after exposure to
      131I, 34,104 patients administered 131I for diagnostic purposes were followed for
      up to 40 years. The mean thyroid dose was estimated as 1.1 Gy, and 67 thyroid
      cancers occurred in contrast to 49.7 expected (standardized incidence ratio =
      1.35; 95% confidence interval 1.05-1.71). Excess cancers were apparent only among
      patients referred because of a suspected thyroid tumor, and no increased risk was
      seen among those referred for other reasons. Further, risk was not related to
      radiation dose to the thyroid gland, time since exposure or age at exposure. The
      slight excess of thyroid cancer thus appeared to be due to the underlying thyroid
      condition and not radiation exposure. Among those under age 20 years when 131I
      was administered, a small excess risk (3 cancers compared to 1.8 expected) was
      about 2-10 times lower than that predicted from data for the A-bomb survivors.
      These data suggest that protraction of dose may result in a lower risk than an
      acute X-ray exposure of the same total dose.

PMID- 8532843
TI  - Radiation hepatology of the rat: association of the production of prostacyclin
      with radiation-induced hepatic fibrosis.
AB  - The hypothesis that hepatic fibrosis is preceded by inflammation and formation of
      prostanoids from arachidonic acid liberated from damaged cell membranes was
      investigated. Liver slices were prepared using a Krumdieck precision tissue
      slicer from sham-irradiated rats or from rats whose livers had been irradiated
      with 25 Gy 137Cs gamma rays in which injury was allowed to develop in vivo for 6
      to 55 days. Unused portions of the liver were analyzed for hydroxyproline content
      to determine hepatic fibrosis. A unique organ culture system was used to incubate
      liver slices for 2 h. Secretion into the incubation medium of aspartate
      aminotransferase and 6-keto prostaglandin F1 alpha were measured to quantify
      damage to the hepatocyte membrane and production of prostacyclin, respectively. A
      threefold increase in the concentration of 6-keto prostaglandin F1 alpha in the
      medium was evident by 13 days after irradiation. This elevated concentration of 6
      keto prostaglandin F1 alpha persisted for the remainder of the study and preceded
      fibrosis, as measured by liver hydroxyproline concentration, and hepatocyte
      membrane damage, as measured by release of aspartate aminotransferase into the
      incubation medium or plasma. We therefore suggest that, in the non-generating
      liver, damage and breakdown of nonparenchymal liver cell membrane is the
      principal source of 6-keto prostaglandin F1 alpha. These results are also
      compatible with the supposition that inflammation and release of arachidonic acid
      metabolites are one of the early biochemical events leading to hepatic fibrosis.
      How the release of arachidonic acid metabolites might initiate and sustain
      radiation-induced fibrosis is discussed. An explanation for the difference in
      liver fibrosis induced by chemicals and radiation is also presented.

PMID- 8532844
TI  - In vitro action of continuous-wave ultrasound combined with adriamycin, X rays or
      hyperthermia.
AB  - We compared the ability of continuous-wave ultrasound to enhance cytotoxicity
      from X irradiation, hyperthermia or exposure to adriamycin. The survival of CHO
      cells exposed in culture medium to these agents was determined with and without
      continuous-wave ultrasound (1.62 or 1.765 MHz). In water-filled transmission
      exposure vessels with 2-cm-diameter Mylar end windows, 10-min insonation not
      producing cytotoxicity could produce .OH radicals (measured by electron
      paramagnetic resonance) even at 0.4 W/cm2. Ultrasound at intensities ranging
      between 1 and 2.5 W/cm2 increased the clonogenic cytotoxicity of adriamycin (P =
      0.0023 by paired t test) but not of X rays (2-10 Gy) or hyperthermia (44 degrees
      C for 10-50 min). The only significant action of continuous-wave ultrasound under
      similar test conditions was the potentiation of adriamycin-induced clonogenic
      cytotoxicity, possibly mediated by cavitational activity.

PMID- 8532845
TI  - The origin of Gaussian distributions of synaptic potentials.
AB  - Spontaneous synaptic potentials were identified at the motor endplate 40 years
      ago. These were shown to possess amplitudes that could be described by a Gaussian
      distribution as could the amplitudes of evoked synaptic potentials under
      conditions of very low probability for secretion. As these Gaussians were
      identical, the idea of a unit or quantum of transmission was conceived. The
      failure to obtain similar Gaussian distributions for both spontaneous and low
      probability evoked potentials during development of endplates indicated that a
      unit of transmission was not operating. However both the spontaneous and very low
      probability evoked potentials could each be described by mixtures of Gaussians
      indicating a subunit of transmission might be operative. There are no ganglionic
      or central synapses at which comparisons have been made between spontaneous and
      low-probability evoked potentials that show each can be described by a Gaussian
      distribution, let alone that these are the same indicating a unit of transmission
      as originally conceived. There is some evidence that mixtures of Gaussians can be
      used to describe both spontaneous and very low-probability evoked synaptic
      potential amplitudes, opening up the possibility for a subunit of transmission at
      these synapses. The vesicle hypothesis, that the quantum of transmission at the
      endplate is due to the exocytosis of the contents of a synaptic vesicle, was also
      enunciated nearly 40 years ago. The existence of subunits of transmission has
      required reconsideration of this hypothesis. Three alternatives are considered:
      in one, the calcium-transient hypothesis, the subunit of secretion is due to the
      release of calcium from one of several calcium stores in the nerve terminal, so
      that several subunits are released when a number of these calcium stores are
      engaged in a regenerative response to the terminal action potential; a second
      alternative, the mediatophore hypothesis, is that a subunit of secretion occurs
      when a single transmitter transport protein channels transmitter across the
      terminal membrane, several such mediatophore proteins acting in concert then give
      multiple subunit release; finally, there is the vesicle fusion-pore hypothesis,
      in which individual transient openings of a fusion-pore channel joining a
      synaptic vesicle to the terminal membrane are responsible for secretion of a
      transmitter subunit, with multiple transients giving several subunits. Perhaps we
      will have distinguished between these possibilities before the quantal hypothesis
      is 50 years old.

PMID- 8532846
TI  - The frog taste disc: a prototype of the vertebrate gustatory organ.
AB  - The frog taste disc (TD) is apparently the largest gustatory organ found in
      vertebrates and seems to differentiate into a specialized variety of the
      prototypic scheme of the taste bud. An explanation for this unusual organization
      is lacking although it is possible to speculate the existence of environmental
      and nutritional requirements. Up to the present time, the most common model of
      the TD was based on two main cell types (sensory and sustentacular). This model
      may oversimplify the morphology of this structure since more numerous cell types
      have been described. We now propose a new model of the TD, based on comprehensive
      data on the ultrastructure of the organ obtained in the last 20 years. The main
      conclusions are the following: (1) the TD is a pluristratified epithelium with a
      general organization similar to that of the olfactory and vomeronasal epithelium;
      (2) it has skeleton composed of three different types of epithelial cells; (3)
      the chemoreceptorial surface is covered by different microenvironments; (4) three
      different types of neuro-epithelial systems are present; the type II is an 'open'
      sensory cell with axonal contacts devoid of vesicles; the type III is an 'open'
      sensory cell with synaptic-like junctions; the type i.v. is a 'closed' sensory
      cell with a 'Merkel-neurite complex'; (5) the nerve fibers in the basal plexus
      are mostly cholinergic while the peridiscal nerve fibers are mostly peptidergic.
      The presence of several cell types in the TD must be considered using these large
      receptors in electrophysiological studies or as a source of isolated cells, and
      their complexity must induce caution in the interpretation of the data. Text
      books of histology usually describe the peripheral structures associated with
      taste as very simple: an idea that probably must be revised. A taste organ is a
      highly complex structure composed of several sensory systems and a comparative
      approach can aid comprehension of its general organization. The study of the
      'large taste organs' present in some species of amphibians can provide useful
      data for knowledge of the gustatory system of vertebrates.

PMID- 8532847
TI  - Amygdala role in conditioned associative learning.
AB  - Amygdala role in emotion was reviewed in reference to recent amygdala lesion
      studies and neuronal responses in the rat amygdala to conditioned stimuli.
      Extensive lesion studies suggest that the amygdala is crucial in various kinds of
      motivated and emotional behavior, and related autonomic responses. These amygdala
      functions critically depend on learning and memory. Amygdala lesions, both before
      and after training of conditioned associative learning, impaired emotional
      expression without simple sensory-motor deficits. Pharmacological experiments
      indicated neurotransmission in the amygdala is mediated through NMDA and AMPA
      receptors. These results strongly suggest the amygdala involvement in acquiring
      and storing associative memory (i.e. stimulus-affect association), by which
      animals recognize and evaluate the biological significance of a stimulus. This
      information is then transferred to the brainstem executing system. In the
      neurophysiological experiments, there were topographic distributions of sensory
      responsive neurons within the amygdala, which were well correlated to anatomical
      data. The responses of rat amygdala neurons changed plastically during learning.
      Furthermore, more sensory-responsive neurons were encountered in the amygdala of
      rats trained to associate the sensory stimuli with a reinforcement than in the
      amygdala of rats that were not trained. In trained rats, multimodal neurons that
      responded to conditioned and unconditioned stimuli were frequently found in the
      basolateral and central nuclei of the amygdala. The results suggest that
      basolateral and central nuclei are foci where various sensory modalities
      converge, and which might perform critical functions in acquiring and storing
      long-term associative memory to link between sensory information and affective
      significance.

PMID- 8532848
TI  - A physiological role for GABAB receptors and the effects of baclofen in the
      mammalian central nervous system.
AB  - The inhibitory neurotransmitter GABA acts in the mammalian brain through two
      different receptor classes: GABAA and GABAB receptors. GABAB receptors differ
      fundamentally from GABAA receptors in that they require a G-protein. GABAB
      receptors are located pre- and/or post-synaptically, and are coupled to various
      K+ and Ca2+ channels presumably through both a membrane delimited pathway and a
      pathway involving second messengers. Baclofen, a selective GABAB receptor
      agonist, as well as GABA itself have pre- and post-synaptic effects. Pre-synaptic
      effects comprise the reduction of the release of excitatory and inhibitory
      transmitters. GABAergic receptors on GABAergic terminals may regulate GABA
      release, however, in most instances spontaneous inhibitory synaptic activity is
      not modulated by endogenous GABA. Post-synaptic GABAB receptor-mediated
      inhibition is likely to occur through a membrane delimited pathway activating K+
      channels, while baclofen, in some neurons, may activate K+ channels through a
      second messenger pathway involving arachidonic acid. Some, but not all GABAB
      receptor-gated K+ channels have the typical properties of those G-protein
      activated K+ channels which are also gated by other endogenous ligands of the
      brain. New, high affinity GABAB antagonists are now available, and some
      pharmacological evidence points to a receptor heterogeneity. The pharmacological
      distinction of receptor subtypes, however, has to await final support from a
      characterization of the molecular structure. The function importance of post
      synaptic GABAB receptors is highlighted by a segregation of GABAA and GABAB
      synapses in the mammalian brain.

PMID- 8532849
TI  - Use of voltage-sensitive dyes and optical recordings in the central nervous
      system.
AB  - Understanding the spatio-temporal features of the information processing
      occurring in any complex neural structure requires the monitoring and analysis of
      the activity in populations of neurons. Electrophysiological and other mapping
      techniques have provided important insights into the function of neural circuits
      and neural populations in many systems. However, there remain limitations with
      these approaches. Therefore, complementary techniques which permit the monitoring
      of the spatio-temporal activity in neuronal populations are of continued
      interest. One promising approach to monitor the electrical activity in
      populations of neurons or on multiple sites of a single neuron is with voltage
      sensitive dyes coupled with optical recording techniques. This review
      concentrates on the use of voltage-sensitive dyes and optical imaging as tools to
      study the activity in neuronal populations in the central nervous system.
      Focusing on 'fast' voltage-sensitive dyes first, several technical issues and
      developments in optical imaging will be reviewed. These will include more recent
      developments in voltage-sensitive dyes as well as newer developments in optical
      recording technology. Second, studies using voltage-sensitive dyes to investigate
      information processing questions in the central nervous system and in the
      invertebrate nervous system will be reviewed. Some emphasis will be placed on the
      cerebellum, but the major goal is to survey how voltage-sensitive dyes and
      optical recordings have been utilized in the central nervous system. The review
      will include optical studies on the visual, auditory, olfactory, somatosensory,
      auditory, hippocampal and brainstem systems, as well as single cell studies
      addressing information processing questions. Discussion of the intrinsic optical
      signals is also included. The review attempts to show how voltage-sensitive dyes
      and optical recordings can be used to obtain high spatial and temporal resolution
      monitoring of neuronal activity.

PMID- 8532850
TI  - Update on cellular transplantation into the CNS as a novel therapy for chronic
      pain.
AB  - The transplantation of cells that secrete neuroactive substances with analgesic
      properties into the CNS is a novel method that challenges current approaches in
      treating chronic pain. This review covers pre-clinical and clinical studies from
      both allogeneic and xenogeneic sources. One cell source that has been utilized
      successfully is the adrenal chromaffin cell, since such cells constitutively
      release catecholamines, opioid peptides, and neurotrophic factors; release can be
      augmented with nicotine. Other graft sources include AtT-20 and B-16 cell lines
      which release enkephalins and catecholamines, respectively. For grafting in
      rodents, adrenal medullary tissue pieces are transplanted to the subarachnoid
      space. Chromaffin cell transplants can decrease pain sensitivity in normal rats
      using standard acute pain tests (paw-pinch, hot-plate, and tail-flick). In
      addition, transplants can restore normal pain thresholds in rodent models of
      chronic pain (formalin, adjuvant-induced arthritis, and sciatic-nerve tie) which
      closely similate the pathologies of human chronic pain conditions. Xenografts
      have been studied due to concerns that future application for human pain may be
      limited by donor availability. Despite immune privileges of the CNS, xenografts
      require at least short-term immunosuppression to obtain a viable graft. Cell
      encapsulation is one method of sustaining a xenograft (in rat and human hosts)
      while circumventing the need for immunosuppression. Clinical studies have been
      initiated for terminal cancer patients with promising results as assessed by
      markedly reduced narcotic intake, visual analog scale ratings, and increased CSF
      levels of catecholamines and met-enkephalin.

PMID- 8532851
TI  - N-acetylaspartate in neuropsychiatric disorders.
AB  - N-Acetyl aspartate (NAA) is the second most abundant amino acid in the human
      brain. NAA is synthesized by L-aspartate N-acetyl transferase or by cleavage from
      N-acetyl aspartyl glutamate by N-acylated alpha-linked L-amino dipeptidase
      (NAALADase); and it is catabolized to acetate and aspartate by N-acetyl aspartate
      amino hydrolase (amino acylase II). NAA is localized primarily to neurons, where
      it is concentrated in the cytosol. Although NAA is devoid of neurophysiological
      effects, it serves as an acetyl donor, an initiator of protein synthesis or a
      carbon transfer source across the mitochondrial membrane. The concentration of
      NAA in human brain increases 3-fold between midgestation and adulthood. In
      Canavan's Disease, an autosomal recessive disorder due to a null mutation in
      amino acylase II, NAA levels in brain are markedly increased and disrupt
      myelination. NAA levels have been found to be reduced in neurodegenerative
      disorders, including Alzheimer's Disease and Huntington's Disease. Since
      endogenous NAA can be readily detected in human brain by magnetic resonance
      spectroscopy, it is increasingly being exploited as a marker for functional and
      structural integrity of neurons in an expanding number of disorders.

PMID- 8532852
TI  - Effects of myotoxins on skeletal muscle fibers.
AB  - This review highlights various aspects of a number of experimental myological
      alterations, induced by different chemical toxicants, including
      anticholinesterase, colchicine, vincristine, chloroquine, tetanus toxin,
      botulinum toxin, reserpine and emetine. Despite their chemical diversity and
      mechanism(s) of action, it is evident from the data discussed here that
      remarkably different toxic agents exert quite similar effects and induce toxic
      myopathies. The latter include preferential involvement of slow-twitch red
      muscle, mitochondrial derangement, denervation-like alterations, formation of
      membranous whorls, tubular aggregates, autophagic vacuoles and axonal sprouts.
      The non-invasive experimental models discussed here are valuable in studying
      various aspects of myopathology in the absence of any mechanical damage to the
      innervating elements from neurons to axonal terminals.

PMID- 8532853
TI  - [In vitro culture and transfer of mammalian early embryos].

PMID- 8532854
TI  - [On transgenic mouse systems].

PMID- 8532855
TI  - [Origin and Nature of the mammalian embryonic stem cell lines].

PMID- 8532856
TI  - [Homologous recombination for gene targeting].

PMID- 8532857
TI  - [Genetic screening for novel genes by insertional mutagenesis with gene trap
      method in ES cells].

PMID- 8532858
TI  - [Chick embryo culture and manipulation of early avian embryo].

PMID- 8532859
TI  - [Mouse model for familial adenomatous polyposis coli and APC gene].

PMID- 8532860
TI  - [A role of AP-1 in proliferation and differentiation of lymphocytes].

PMID- 8532861
TI  - [Abnormal T-cell differentiation and development of T-cell lymphomas in TL
      transgenic mice].

PMID- 8532862
TI  - [Bcl-2 with anti-apoptotic activity].

PMID- 8532863
TI  - [Chronic rheumatoid arthritis model mice transgenic for the HTLV-I tax gene].

PMID- 8532864
TI  - [Nonspecific host defense mechanism by macrophages--analysis by NF-IL6 deficient
      mice].

PMID- 8532865
TI  - [Regulation of T cell development by T cell receptor complex--analysis by TCR-CD3
      chains-deficient mice].

PMID- 8532866
TI  - [Analysis of regulatory mechanism for humoral immunity using transgenic mice of
      rearranged immunoglobulin genes].

PMID- 8532867
TI  - [Gamma delta T cells--gene to biology].

PMID- 8532868
TI  - [Targeted ablation of transcription factor genes].

PMID- 8532869
TI  - [Mice carrying null mutations of the homeotic genes Hoxa10 and Msx1].

PMID- 8532870
TI  - [Function of Hox genes in formation of skeletons].

PMID- 8532871
TI  - [The mouse embryogenesis of jumonji mutant obtained by gene-trap method].

PMID- 8532872
TI  - [The roles of Wnt genes during mouse development].

PMID- 8532873
TI  - [Molecular mechanism of learning and memory with genetics].

PMID- 8532874
TI  - [Excitation-contraction uncoupling and muscular degeneration lacking functional
      skeletal muscle ryanodine-receptor gene].

PMID- 8532875
TI  - [Morphological analysis of NCAM-180 deficient mouse brain--polysialic acid moiety
      and neuronal migration].

PMID- 8532876
TI  - [Animal models for muscle research and muscle diseases].

PMID- 8532877
TI  - [An attempt to generate a closer mouse model of familial amyloidotic
      polyneuropathy, an autosomal dominantly inherited disease].

PMID- 8532878
TI  - [Mice with targeted DNA repair genes].

PMID- 8532879
TI  - [Transgenic rat].

PMID- 8532880
TI  - [Transgenic rabbit].

PMID- 8532881
TI  - [Current status and challenges in the production of transgenic pigs].

PMID- 8532882
TI  - [Transgenesis and ES cell lines in Medaka].

PMID- 8532883
TI  - [Transgene expression and integration in the zebrafish, Danio rerio].

PMID- 8532884
TI  - [Transgenic bird].

PMID- 8532885
TI  - [About K+ channels].

PMID- 8532886
TI  - [Molecular structure and function of voltage-dependent K channels].

PMID- 8532887
TI  - [Primary structure and biophysical properties of inward rectifier K+ channels].

PMID- 8532888
TI  - [Molecular mechanism of the G protein regulation of inwardly rectifying potassium
      channels].

PMID- 8532889
TI  - [A pH-sensitive K+ channel].

PMID- 8532890
TI  - [Molecular evolution of voltage-gated ion channels].

PMID- 8532891
TI  - [Prion-like cytoplasmic genetic determinants of the budding yeast: conformations
      and biological functions of protein].

PMID- 8532892
TI  - [Anandamide: a marijuana-like compound produced in animal tissues].

PMID- 8532893
TI  - [Shed light on the molecular structure of the respiratory chain: X-ray crystal
      structure analysis of cytochrome c oxidase].

PMID- 8532894
TI  - [Fiber optic chemical gas sensors based on environmental chromism].

PMID- 8532895
TI  - [Simple detection of the contamination in animal cell cultures].

PMID- 8532896
TI  - ["New" authoritarianism and right extremism. A time-related diagnostic
      conjecture].
AB  - On the basis of two brief case studies the author elucidates the difference
      between "classical" authoritarianism as described by Adorno et al and the "new"
      authoritarianism which she posits as indicating what might be termed a negatively
      extended stage of sociation. Whereas the classical authoritarian takes an
      external object as the locus for the formation of moral judgments and activates
      aggressive impulses via projections onto "foreigners" or "aliens", the
      communicative dimension of social action, a dimension profoundly characterised by
      narcissism and centring no longer around the super-ego but the unconscious self
      with a specific aggression potential of its own. In Brede's view extreme right
      wing phraseology and violence may be a reaction to persons or groups whose common
      factor is the "new" authoritarianist syndrome.

PMID- 8532897
TI  - [Psychoanalytic theory and therapy of neurotic anxieties].
AB  - In the author's view anxiety is a psychosomatic phenomenon that develops into
      neurotic anxiety when unconscious psychic components come into play. He regards
      it as impossible to make a clear-cut distinction between neurotic anxiety and
      real anxiety given that anxiety neuroses also display an element of historical
      and continuing actuality and can thus be said to have "real" foundations. In his
      discussion of treatment techniques, Thoma introduces following Weiss and Sampson
      the concept of "mastering" to refer to the necessity of understanding the
      repetitions and transferences of the patient as an attempt to master traumatic
      situations with the assistance of the analyst. In his view it is not sufficient
      to make the patient aware of libidinous and aggressive drives but rather to
      broaden the scope of action available to the patient.

PMID- 8532898
TI  - [Psychoanalytic theories of hypochondria].
AB  - Although hypochondria is one of the earliest psychic conditions to be described,
      its nosological status is still uncertain and it has been largely neglected in
      theories of psychosomatics and neurosis. The authors undertake a detailed review
      of the literature and examine the psychodynamic concepts and theoretical
      approaches to the hypochondria phenomenon, from Freud, Ferenczi and Levy, through
      Klein and the ego psychologists, object-relation theories and the psychology of
      the self, all the way up to the present day. The authors trace the differences
      between hypochondria and other body-related disturbances and indicate the
      consequences for diagnosis and therapy.

PMID- 8532899
TI  - Stimulus spacing effects in temporal bisection by humans.
AB  - Two experiments studied the bisection of sets of stimulus durations (ranging from
      200 to 800 msec, or 100 to 900 msec) by normal adults. In Experiment 1, two
      bisection techniques were used: a "similarity" method, where subjects had to
      classify each duration in terms of its similarity to the shortest and longest
      members of the set (which were explicitly identified as Short and Long
      standards), or a "partition" method, where subjects simply classified each
      duration as Short or Long, without explicit standards. For different groups, the
      durations within each set were spaced either linearly or logarithmically between
      the longest and shortest members. The two bisection methods produced similar
      results, but psychometric functions (proportion of Long judgements versus
      stimulus length) were shifted to the left in the logarithmic conditions relative
      to the linear ones--that is, some shorter durations were classified as Long more
      frequently in logarithmic conditions. Experiment 2 used arithmetic, but unequal,
      stimulus spacings between the shortest and longest set members, and the partition
      method. Sets containing more shorter than longer durations had psychometric
      functions shifted to the left relative to sets with more longer than shorter
      durations. The data suggest that judgement of some time value, t, depends on the
      context in which t appears, not only on its value relative to the longest and
      shortest set members (as most current theories of bisection propose). A model
      assuming that judgements of t are based on the relation between t and the
      arithmetic mean of all the durations in the set fitted data reasonably well in
      most conditions. This model, furthermore, incorporated decision rules used to
      account for human performance on temporal generalization tasks, thus promoting
      theoretical integration of the two sorts of experiments.

PMID- 8532900
TI  - Extinction of within-event learning is contextually controlled and subject to
      renewal.
AB  - Five experiments examined within-event learning in rats by inducing an appetite
      for one of the elements (salt) of a compound stimulus and assessing preference
      for the other element (almond). Almond preference was conditional upon (1) the
      almond flavour having been presented in compound with the salt, and (2) the
      assessment being conducted when the rats were out of sodium balance (Experiment
      1). Presentations of the compound in one environment (A) and of the salt and
      almond elements in a second environment (B) resulted in greater almond preference
      when rats were tested in A than in B (Experiment 2). Almond preference was
      reduced when separate presentations of the compound and almond (Experiment 3) or
      of the compound and salt (Experiment 4) occurred in the same environments but not
      when these presentations occurred in different environments. Rats exposed to the
      compound in A and then extinguished to the elements in either A or B showed a
      reduced almond preference when tested in the extinction environment, but not when
      tested in the other environment (Experiment 5). Thus, extinction of within-event
      learning is context-specific and subject to renewal. The results were interpreted
      in terms of an associative model whereby separate presentations of the elements
      result in a symmetrical inhibitory link which is contextually gated (Bouton,
      1993).

PMID- 8532901
TI  - Radiotherapy results in early stage low grade nodal non-Hodgkin's lymphoma.
AB  - This is a retrospective review of stages I and II low grade nodal non-Hodgkin's
      lymphoma (NHL) seen at the Royal Marsden Hospital and treated with radiotherapy
      alone. From January 1970 to December 1989, 58 patients were treated. The Ann
      Arbor staging system was modified to subdivide stage II into localised and
      extensive disease, with localised disease representing no more than two
      contiguous regions. There were 40 stage I patients and 18 stage II patients
      (eight localised and 10 extensive). Volume of the radiotherapy was involved field
      only in 30 patients and extended fields in 28 patients. The median dose was 40 Gy
      in 20 fractions. The pattern of relapse was assessed as being systemic or within
      the standard volume. Survival and progression-free survival (PFS) were
      calculated. Prognostic variables of age, histology, stage and radiotherapy volume
      were analysed by multivariate analysis. The 5- and 10-year PFS for the total
      group were 59 and 43%, and corresponding OS figures were 93 and 79%. Age less
      than 60 years was a predictor of improved survival but not for PFS and we found
      no significance in histology, stage or extent of radiotherapy field for the other
      variables. All relapses occurred with disease outside the original volume, with
      three patients also relapsing in-field. Treatment of this disease produced an OS
      at 10 years of 79%. The plateau on the PFS plot suggested that some patients are
      cured. Young age was the only prognostic factor found for survival. Relapse is
      most frequently outside the treated volume. Our current treatment policy for
      stage I and II low grade NHL is involved field radiotherapy to a dose of 35 Gy in
      20 fraction over 4 weeks.

PMID- 8532902
TI  - Tangential breast irradiation with or without internal mammary chain irradiation:
      results of a randomized trial.
AB  - A prospective randomized study was made of 270 patients with unilateral stage I
      or II invasive breast cancer treated by segmental resection, axillary dissection
      and radiation at the University Hospital of Tampere, Finland, between 1989 and
      1991. The aim of the study was to determine whether there is any advantage or
      disadvantage if the internal mammary chains (IMC) are included in the radiation
      target volume. The medial and lateral two-field technique was used and the target
      volumes were determined randomly either to include the internal mammary chain
      (IMC-RT) or not (no-IMC-RT). The prevalence of radiation pneumonitis was 16% and
      there was no significant difference between the IMC- and no-IMC-groups (18 vs.
      14%). Skin reactions were equal in both groups. Lung fibrosis was more common in
      the IMC-RT group. IN CONCLUSION: radiation of internal mammary chain after
      conservative surgery does not lead to an increase in clinically important skin or
      pulmonary complications. Whether it prevents recurrences or new primaries of the
      opposite breast is too early to say because of the short follow-up time.

PMID- 8532903
TI  - Does tumor control decrease by prolonging overall treatment time or interrupting
      treatment in laryngeal cancer?
AB  - PURPOSE: To evaluate treatment results of radiotherapy in laryngeal cancer and to
      retrospectively investigate the influence of treatment interruptions on local
      control rates. A multivariate analysis was performed to investigate the role of
      overall treatment time on local control rates. MATERIAL AND METHODS: From 1962 to
      end 1986, 864 patients with cancer of the larynx were treated with primary
      radiotherapy, with a variation of doses and treatment times. In 352 patients a
      systematic interruption of 2 weeks was done after 50 Gy (split-course). Local
      control rates were calculated by the actuarial method. A multivariate analysis
      was subsequently performed in order to identify independent variables influencing
      local control rates. RESULTS: The univariate analysis showed that in patients
      treated with a split-course schedule, local control rates were significantly
      lower in glottic cancer (p < 0.001), with differences of 7% in T1 (p = 0.05) and
      11% in T2 (p = 0.11). In node-negative supraglottic cancer a difference of 10% (p
      = 0.16) was observed. The multivariate analysis showed the following factors to
      significantly influence local control: site, total dose, total treatment time, T
      and N stage. Split-course treatment was not an independently significant factor,
      probably caused by time being a stronger factor. In subgroup analysis, the effect
      of total treatment time remained statistically significant in T2 glottic cancer.
      CONCLUSION: A significant negative influence of treatment interruption was seen
      in glottic cancer, and a trend toward significance in node-negative supraglottic
      cancer in univariate analysis. A multivariate analysis showed a negative
      influence of prolonging treatment time in the total patient group. The effect
      remained significant in T2 glottic cancer in subsequent subgroup analysis,
      possibly due to the fact that there is little variation in tumour volume in this
      group. In larger tumours, where there is substantial variation in tumour volume
      and a higher probability of heterogeneity in radiosensitivity, the effect of dose
      time variations could be more difficult to discern.

PMID- 8532904
TI  - Radiotherapy for T2 and T3 carcinoma of the bladder: the influence of overall
      treatment time.
AB  - The influence of overall treatment time on local control rate was studied on a
      group of 147 patients with muscle invasive T2 or T3 transitional cell carcinoma
      of the urinary bladder. All patients received external radiotherapy at the
      Catharina Hospital, Eindhoven, The Netherlands between January 1974 and December
      1984. Patients treated with overall treatment times shorter than 75 days (n = 92)
      were irradiated during a continuous course; all but one patient, with overall
      treatment times of 75 days or more (n = 55), received split-course radiotherapy.
      Actuarial local relapse-free probability at 3 years (LRFP3) was computed from the
      onset of radiotherapy. LRFP3 proved to be dependent on overall treatment time.
      For T2 stage, LRFP3 was 80 +/- 18% (n = 5) and 54 +/- 13% (n = 13) for overall
      times between 15-44 and 45-74 days, respectively, 36 +/- 14% (n = 11) for overall
      times between 75 and 104 days and 64 +/- 15% (n = 11) for overall times longer
      than 105 days. For T3 stage, LRFP3 was 33 +/- 19% (n = 6) and 48 +/- 10% (n = 25)
      for overall times between 15-44 and 45-74 days, respectively, 25 +/- 14% (n = 12)
      for overall times between 75 and 104 days and 22 +/- 14% (n = 9) for overall
      times longer than 105 days. The figures between brackets are numbers of patients
      relapsing within 3 years or at risk of relapse during at least 3 years. Patients
      who died without local relapse before 3 years were censored. We have reasons to
      believe that patient selection bias leads to overestimation of LRFP3 for the
      split-course radiotherapy in retrospective studies where the 'intention to treat'
      cannot be recalled. This retrospective study suggests that prolonging overall
      time of radiotherapy has an effect on local control in T2 and T3 transitional
      cell carcinoma of the urinary bladder. Local control was the worst for patients
      treated by split-course radiotherapy with a gap of approximately one month. Local
      control was not further decreased (and seemed even improved) by longer gaps, but
      this observation is possibly biased as explained in the discussion section. For
      patients treated by continuous course radiotherapy we could not find a difference
      in local control rates between patients treated with overall times of 44 days or
      less and those treated with overall times of 45-74 days.

PMID- 8532905
TI  - Studies with bromodeoxyuridine in head and neck cancer and accelerated
      radiotherapy.
AB  - Using bromodeoxyuridine (BrdUrd), tumour cell proliferation was assessed, by flow
      cytometric (FCM) and immunohistochemical methods, in patients treated by the
      CHART regime of radiotherapy. Of 115 cases studied, data were complete in 90
      using both methods. No cell kinetic-related parameter predicted the outcome of
      patients treated by CHART, in keeping with the view that, with this regime,
      cellular proliferation had been minimised as a cause of failure. Histological
      evaluation of the labelling index (LI) revealed a trend for higher LI is in
      diploid tumours (16.2%) than in aneuploid (13.8%), contrasting to that found by
      FCM (5.0 and 9.3% respectively). When the Tpot was calculated using a combination
      of histology LI and FCM TS, diploid tumours showed more rapid proliferation (Tpot
      1.8 days) than aneuploid tumours (Tpot 3.2 days); this finding was significant (p
      < 0.02). A novel parameter, termed proliferation pattern, unique to these studies
      with BrdUrd in vivo, was assessed. Both proliferation pattern and histological
      grading had predictive power to discriminate the outcome in univariate analysis
      (p = < 0.031 and 0.037, respectively). In a Cox multivariate analysis,
      proliferation pattern was the more important predictor. The studies reported
      highlight the extra information that can be gained from combining
      immunohistochemistry with flow cytometry to study the cellular proliferation of
      human tumours.

PMID- 8532906
TI  - Single-dose radiotherapy (6 Gy): palliation in painful bone metastases.
AB  - Approximately 50% of patients with cancer develop bone metastases and these have
      an important influence on the quality of life. PURPOSE OF THE STUDY. To evaluate
      a lower dose than the one already proven to be effective (8 Gy) in the palliation
      of painful bone metastases. METHODS AND MATERIALS. In a prospective study we
      analyzed the pain relief, after a single dose of 6 Gy, in 170 patients with
      painful bone metastases. This was assessed by a questionnaire. RESULTS. A degree
      of pain relief, was achieved in 88% of the treatments and there was complete
      relief in 39%. When the treatment was given to the vertebrae, infield spinal cord
      compression developed in 9%, and when given to the pelvis or femur, infield
      fractures developed in 8%. CONCLUSION. We concluded that a single dose of 6 Gy
      was very effective in the palliation of painful bone metastases.

PMID- 8532907
TI  - Hyperfractionation in the reirradiation of head and neck cancers. Result of a
      pilot study.
AB  - Between November 1988 and May 1992, 19 patients were enrolled in a pilot study to
      evaluate feasibility and results of a hyperfractionated reirradiation in the
      treatment of head and neck recurrences or second primary tumors developed in
      previously irradiated volume. Patients were divided in two groups according to
      the initial treatment before reirradiation: group 1 included 14 patients treated
      with radical surgery and reirradiated because histological evidence of positive
      margins and/or extra capsular spread of tumor in lymph node metastases; group 2
      included five patients treated with three cycles of CDDP-5FU for unresectable
      tumors and reirradiated because they experienced a complete or good partial (> or
      = 80%) response after chemotherapy. The reirradiation planned dose was 60 Gy in 5
      weeks, with two daily fractions of 1.2 Gy spaced by 6-8 h intervals.
      Reirradiation was delivered exclusively with photon beams in 17 cases and with a
      combination of photon and electron beams in two cases. Follow-up ranged from 3 to
      45 months with a median of 17 months. Of the 19 patients, 13 received the
      reirradiation scheduled dose of 60 Gy. For the six remaining patients, the
      reirradiation doses ranged from 45.6 to 57.6 Gy. All patients experienced an
      acute mucositis which never led to interruption of treatment. Of the 14 patients
      of group 1, 10 died 3-41 months after reirradiation (mean: 14 months), three were
      disease-free 16-37 months after reirradiation and one patient was alive with
      local progressive disease 39 months after the reirradiation. The overall local
      control within reirradiated volume was 36% before and 43% after salvage surgery.
      For all group 1 patients, 12- and 24-month overall survival was 64 and 36%,
      respectively (mean: 21 months). All patients of group 2 presented a local failure
      within the reirradiated volume. Three of them died 12, 16 and 25 months after
      reirradiation, while two of them were alive with progressive disease 25 and 30
      months after reirradiation, respectively. The mean survival was 22 months.
      Overall, 15 late complications were noted: five grade 1, eight grade 2 and two
      grade 3. There was no lethal complication. Four patients alive in September 1993,
      and whose initial technical files were available, were enrolled in an additional
      study to assess the cumulative doses delivered by the two irradiations. Despite
      disappointing loco-regional control rates, a reirradiation of 60 Gy using a
      hyperfractionated schedule is feasible in terms of acute and late toxicity.

PMID- 8532908
TI  - Radiation-induced lung damage after thoracic irradiation for Hodgkin's disease:
      the role of fractionation.
AB  - PURPOSE: to estimate the alpha/beta ratio for damage to human lung after thoracic
      irradiation for Hodgkin's disease. PATIENTS AND METHODS: The criterion for lung
      injury was the presence of radiological changes in the vicinity of the
      mediastinum as assessed on regular follow-up chest X-ray examinations. Patients
      with supradiaphragmatic stage I-II Hodgkin's disease received mantle field
      irradiation as part of their treatment between 1964 and 1981 (E.O.R.T.C.
      protocols H1, H2, and H5). The total mediastinal doses fixed by the protocols
      were 35-40 Gy. The fractional doses were left to the decision of the physicians
      in charge: the most frequent regimens were 5 x 1.8, 5 x 2.0, 4 x 2.5 and 3 x 3.3
      Gy per week. The data were fit to the linear-quadratic (L.Q.) model using time-to
      injury as endpoint. RESULTS: 1048 (97%) of 1082 patients were evaluable. The mean
      follow-up duration was 8 years. One hundred and ninety-five cases of
      radiologically-visible lung damage were observed after a median interval of 6
      months (range: 0-101). The 3-year actuarial probability of lung damage was 19%
      (95% confidence limits: 17, 21). Multivariate analysis (Cox model, stratified by
      protocol) showed an increased risk of damage with dose per fraction (relative
      risk, R.R. = 2.22 per Gy (1.75, 2.82)), the presence of systemic symptoms (R.R. =
      1.53 (1.09, 2.15)), and total mediastinal dose (R.R. = 1.06 per Gy (1.01, 1.12)).
      Age, sex, histological type, number of involved nodal sites and radiotherapy
      duration did not significantly modify the risk of lung damage. The L.Q. model
      parameters were: alpha = 0.031 Gy-1 (0.003, 0.059), beta = 0.010 Gy-2 (0.007,
      0.013), alpha/beta = 3.07 Gy (-0.23, 8.46). CONCLUSION: this low alpha/beta ratio
      is consistent with late effects values from animals and humans, and illustrates
      the influence of large fraction sizes on the occurrence of late pulmonary
      complications.

PMID- 8532909
TI  - The prognostic significance of accumulation of p53 protein in stage III non-small
      cell lung cancer treated by radiotherapy.
AB  - In the present study the prognostic significance of accumulation of nuclear p53
      protein on survival and freedom from local progression was investigated. Formalin
      fixed, paraffin-embedded sections obtained by bronchoscopy or mediastinoscopy
      were used to examine the expression of nuclear p53 protein using
      immunohistochemistry. In 37 cases (57%), overexpression of the p53 protein was
      detected. No relation was found between p53 expression and other pretreatment
      variables. Response to radiotherapy was found in 11 p53-negative cases (65%)
      versus 10 p53-positive cases (42%). Freedom from local progression was
      significantly better in the p53-negative cases as compared with the p53-positive
      cases. The p53-negative cases who responded to radiotherapy showed an excellent
      freedom from local progression rate after 2 years of 100%, whereas all p53
      positive cases without response to radiotherapy showed local progression within
      24 months. Overall survival between p53-negative and -positive cases did not
      differ, however the disease-specific survival was found to be worse in the p53
      positive cases as compared to the negative cases (median survival 8.4 vs. 14.4
      months (P < 0.05)). No correlation was found between p53 expression and the
      frequency of distant metastases. In conclusion, the results of this study suggest
      that p53 protein expression may be of prognostic value on freedom from local
      progression in non-small cell lung carcinoma.

PMID- 8532910
TI  - Nicotinamide pharmacokinetics in patients.
AB  - Pharmacokinetic analyses were performed on blood samples of 12 patients
      undergoing treatment with nicotinamide, hyperthermia and radiation therapy for a
      variety of recurrent/metastatic cancers. Escalating oral doses of 3, 4, 5, 6 and
      10 g of nicotinamide showed a linear relationship between maximum recorded plasma
      concentrations and the dose in grams (correlation coefficient, r = 0.91). Maximum
      plasma levels were observed by 30 min in most patients ingesting up to 6 g of
      nicotinamide. In marked contrast, five out of six patients ingesting 10 g of
      nicotinamide demonstrated increasing plasma levels at least up to 3 h post
      ingestion. Doses up to 6 g were well tolerated and resulted in average maximum
      recorded plasma levels (mean +/- 1 SEM) of 156.4 +/- 33.6 micrograms/ml. Doses of
      10 g were generally not well tolerated, but a high plasma level was maintained on
      average for at least 4 h. Plasma concentrations of the above order have been
      previously associated with maximal enhancement of radiation damage in mouse tumor
      models. This suggests that radiosensitization can be expected to occur in human
      tumors following oral administration of a safe and well tolerated dose of 6 g.
      However, at higher doses (i.e., 10 g), the pharmacokinetics, and perhaps
      radiosensitization, may differ markedly.

PMID- 8532911
TI  - Quality assurance of the EORTC radiotherapy trial 22863 for prostatic cancer: the
      dummy run.
AB  - The results of a dummy run involving nine centers participating in a study
      comparing radiotherapy alone with radiotherapy plus hormone therapy in patients
      with high metastatic risk prostatic cancer (EORTC protocol 22863) show that, in
      all centers but one, patients are treated in the same way. However, they have
      also indicated that protocol compliance could be improved by a better assessment
      of the target volume, by taking into account of the use of protective shields and
      of variations in radiological density, by determining beam position on a large
      number of slices, and by the use of CT scan images for treatment planning.

PMID- 8532912
TI  - Quality assurance in the CHART clinical trial.
AB  - As part of the clinical trial of CHART (continuous hyperfractionated accelerated
      radiotherapy) a quality assurance programme was included. The technical part of
      this--which is reported in this paper--is a series of tests designed to check all
      aspects of treatment planning and delivery. The results of visits to the 13
      participating centres--and repeat visits to some of these centres--are discussed.
      The main areas tested were as follows. The linear accelerator: mechanical, and
      optical, scales and indicators; radiation field size; flatness and symmetry.
      DOSIMETRY: output; wedge factor; beam energy; phantom measurements against a plan
      calculated by the centre. SIMULATOR: mechanical, optical scales and indicators.
      The results show these centres work within the tolerances chosen for most
      parameters. Flatness, wedge factor and energy were areas of weakness in some
      centres. This must be partly the cause of the spread of phantom measurements
      which, after removal of variations in output, still range from -7 to +6% between
      calculated and measured values.

PMID- 8532913
TI  - Prediction of normal-tissue tolerance from in vitro cellular radiation
      sensitivity.

PMID- 8532914
TI  - Mental health in remote rural developing areas. Concepts and cases. Committee on
      Therapeutic Care. Group for the Advancement of Psychiatry.

PMID- 8532915
TI  - Adolescent depression: relationships of self-report to intellectual and adaptive
      functioning.
AB  - Self-report measures of depression, general psychopathology, and social skills
      were administered to adolescents ranging from moderate mental retardation to
      above normal intelligence. Adolescents with mental retardation reported more
      depression and general psychopathology symptoms. Variance and regression analyses
      demonstrated distinctions on the basis of mental retardation status for
      individual measures. Additional analyses identified differences between
      individuals with above normal intelligence and individuals with mild mental
      retardation on the basis of depression specifically. Adaptive behavior functioned
      as a moderator variable, mediating the relationship between depression and
      intellectual functioning.

PMID- 8532916
TI  - Enhancing the recognition and production of facial expressions of emotion by
      children with mental retardation.
AB  - The ability to recognize and respond appropriately to facial expressions of
      emotion is essential for interpersonal interaction. Individuals with mental
      retardation have problems not only in recognizing but also in accurately
      producing facial expressions of emotion. In Experiment 1, directed rehearsal was
      used to teach six boys with mild and moderate mental retardation to increase
      their ability to recognize facial expressions of emotion. In addition, their
      ability to produce the six basic facial expressions of emotion was periodically
      assessed throughout the study. The results showed that the boys' accuracy in
      recognizing facial expressions of emotion increased rapidly with instruction and
      that their increased accuracy was maintained at 8- and 12-week assessments
      following the termination of instruction. However, their increased levels of
      recognition did not generalize to the production of these emotions. In Experiment
      2, four boys who had participated in the first study were provided with directed
      rehearsal training in the production of the six basic facial expressions of
      emotion. Their ability to produce facial expressions of emotion increased with
      instruction and was maintained following the termination of instruction. In
      addition, independent raters judged that the boys' production of these emotions
      matched the emotions that they were required to produce, suggesting a socially
      valid behavior change. These studies showed that the ability of children with
      mental retardation to recognize and produce facial expressions of emotion can be
      enhanced through instruction.

PMID- 8532917
TI  - The relationships among facial emotion recognition, social skills, and quality of
      life.
AB  - Forty-six adults with mild or moderate mental retardation living in a large
      residential facility were administered the socialization domain of the Vineland
      Adaptive Behavior Scales, a subjective measure of quality of life, and a facial
      emotion recognition test. There were significant differences in accuracy of
      emotion recognition among specific emotions. However, the only significant
      correlate of facial emotion recognition was IQ. Possible relationships among
      facial emotion recognition and basic versus more subtle indices of socialization
      are explored.

PMID- 8532918
TI  - Facial emotion recognition by persons with mental retardation: a review of the
      experimental literature.

PMID- 8532919
TI  - Teaching key use to persons with severe disabilities in congregate living
      settings.
AB  - Key use remains overlooked for increasing independent material use by persons
      with severe mental retardation. In Experiment 1, a procedure to train key
      locating was evaluated in a multiple-probe withdrawal design across three groups
      of participants. Most participants located their keys when reinforced for doing
      so; however, key locating decreased when the reinforcement procedure was
      withdrawn. In Experiment 2, a multiple probe design across four participant
      groups was used to evaluate a training procedure to teach key use. Twenty of 25
      participants used a key to open and lock their personal lockers as a result of
      training. However, only 36% of the participants were able to use their keys
      without prompts from experimenters.

PMID- 8532920
TI  - [The importance of antibiotic prophylaxis in surgery].

PMID- 8532921
TI  - [The effect of surgical antibiotic prophylaxis and the timing of its
      administration on the risk of surgical wound infection].
AB  - BACKGROUND: Clinical trials have demonstrated the efficacy of surgical
      prophylaxis (SP). Nevertheless, how the timing of antibiotic administration
      influences the risk of infection in clinical praxis has scarcely been studied. In
      this study an assessment was made of whether the non administration of
      antibiotic, or its administration longer than 2 hours preoperatively, or only
      postoperatively, are associated with a higher rate of infection of the surgical
      wound (SWI) compared with antibiotic administration within the two hours prior to
      surgery in our setting. METHODS: Observational, longitudinal, pseudoretrospective
      study. It included 2,483 patients undergoing surgery in 1992, with clean
      contaminated, contaminated and clean with prophylaxis indication, and without
      previous infection surgeries. Information on variables potentially associated
      with SWI and incidence of infection was monitored. A multivariate analysis was
      made by means of the logistic regression method to evaluate the association of
      prophylaxis and time of administration, controlling for the remaining variables.
      RESULTS: 754 patients received appropriate prophylaxis (within 2 hours prior to
      surgery); 28 of these patients (3.7%) developed SWI. Twenty-four of the 107 who
      received prophylaxis longer than 2 hours prior to surgery developed infection
      (22.4%; p < 0.001 compared with the first group; OD: 7.5, 95% CI: 3.94-14.1); in
      the group of patients non receiving preintervention doses 94 patients developed
      infection (7.7%; p = 0.001; OR: 2.16, 95% IC: 1.38-3.41). Among patients who did
      not receive prophylaxis 24 infections were detected (6%; p = 0.10; OR: 1.66, 95%
      CI: 0.91-2.99). In the multivariate analysis the administration of prophylaxis
      longer than 2 hours prior to surgery or postoperatively was confirmed to be
      associated with a higher SWI rate, as in the non-administration situation,
      controlling for the remaining variables (OR for longer than 2 hours: 5.82; for
      postoperative administration: 3.23, and for non-administration: 2.68).
      CONCLUSIONS: The administration of SP is inappropriate in a high percentage of
      cases. The administration of SP within the 2 hours prior to surgery reduces the
      risk of SWI, compared with the administration 2 hours or longer prior to
      intervention or only postoperatively.

PMID- 8532922
TI  - [Serum hepatitis B markers: atypical patterns detected at the Hospital Insular de
      Gran Canaria].
AB  - Two atypical serological markers of hepatitis B virus (HBV) infection were
      detected in 19 patients during a 18-month period study. Pattern 1 (10 patients)
      was consistent with HBV-2 infection. Reactivity of HbsAG was confirmed by
      neutralization tests; the absence of other markers was also verified, included
      anti-HBcIgM. Three of the patients were classified in high risk groups and seven
      in the low risk groups for hepatitis B; in none of them was co-infection with
      hepatitis A virus (HAV) detected. Pattern 2 (9 patients) was characterized by the
      detection of HBsAg and HBeAg and the absence of other hepatitis B markers. Six of
      these patients were HIV-positive patients and had increased and persistent levels
      (for longer than 12 weeks) of these markers. In the three remaining patients
      (with no underlying immunological disorders) there was a loss of these markers
      within a variable time (2 days to 16 weeks). Nevertheless, DNA-VHB was detected
      in one of these serum samples once all markers of virus B had disappeared.

PMID- 8532924
TI  - [The Gorlin syndrome. A review of 11 cases].
AB  - Gorlin syndrome is an autosomal dominant disorder with variable penetrance and
      expressivity. It is characterized by early onset of multiple basal cell
      carcinomas, mandibular keratocytes, pits of the palms and soles, cerebral ectopic
      calcification and several skeletal anomalies. We report a series of eleven
      patients (eight females and three males) with Gorlin syndrome, belonging to nine
      different families, which have been diagnosed in our Dermatology department
      during the last ten years. The ages at the moment of diagnosis ranged from 8 to
      73 years. Ovarian fibromas were demonstrated in five cases and a frontal
      parasagittal meningioma in one case. Gorlin syndrome has been recently linked to
      a putative tumor suppressor gene which has been mapped to 9(q22.3-q31). Further
      research on the function of the protein encoded by this gene may provide
      additional insight on the mechanisms leading to oncogenesis in sporadic and
      hereditary basal cell carcinomas and other tumors.

PMID- 8532923
TI  - [Noninvasive ventilator support in patients with chronic obstructive pulmonary
      disease. A comparison of 2 methods].
AB  - The external high frequency oscillation around a negative baseline (EHFO-NB) is a
      new mode of non-invasive ventilatory support which could replace or complement
      nasal intermittent positive pressure ventilation (NIPPV) for treatment of
      patients with chronic obstructive pulmonary disease, both in the decompensation
      phases and as preventive measure in intercrisis periods. This was a prospective
      study in which tolerance and short term effects on acid-base balance and gas
      interchange of both NIPPV and EHFO-NB in twenty patients with severe chronic
      obstructive pulmonary disease were compared. With both methods similar decrease
      in PaCO2 and increases in pH were observed, with decrease and increase in
      respiratory frequency when using NIPPV and EHFO-NB, respectively; the latter in
      association with the high oscillation frequencies used. While an improvement of
      SaO2 and no changes in PaO2 and intrapulmonary shunt were observed on NIPPV, a
      decrease was observed in the SaO2 and an increase in the shunt on EHFO-NB.
      Comfort of patients, improvement of perceived sensation of dyspnea, and the
      absence of complications were similar with both methods. While on NIPPV, 75 per
      cent of patients required a short period of training and continuous supervision.

PMID- 8532925
TI  - [Multiple organ failure in Plasmodium falciparum malaria].
AB  - A 44-year-old Spanish woman travelled in Kenya without doing correct malarial
      prophylaxis. Upon her return to Spain, she suffered from Plasmodium falciparum
      malaria. She was initially treated with chloroquine for three days, but her state
      worsened and she was admitted to our intensive care unit. On admission,
      parasitaemia was 22%. She had hyperpyrexia, obtundation, hypotension,
      tachycardia, tachypnoea, jaundice, digestive haemorrhage, petechiae in her soles,
      oliguria with elevation of serum uraemia and creatinine, anaemia,
      thrombocytopaenia, hypoproteinaemia, hyponatraemia, hypocalcaemia, metabolic
      acidosis and parameters of disseminated intravascular coagulation. She was given
      quinine, sulfadoxine-pyrimethamine and clindamycin. An exchange transfusion was
      performed, during which an acute pulmonary oedema appeared, initially with high
      pulmonary artery wedge pressure. She required mechanical ventilation for 16 days
      and haemodialysis for 11 days. She remained in coma and had seizures which
      required diazepam, phenitoin and thiopentone. She received a total amount of 22
      units of packed erythrocytes, 55 of platelets and 15 of plasma. After the first
      week, she had nosocomial infection due to Escherichia coli, Staphylococcus and
      Pseudomonas aeruginosa and was treated with the corresponding antibiotics. She
      cured completely. This case report gives us the possibility of discussing on
      frequent problems in the prevention and treatment of malaria, and on the
      treatment of severe, life-threatening malaria in the setting of the intensive
      care unit.

PMID- 8532926
TI  - [The current outlook in the treatment of the acute respiratory distress
      syndrome].

PMID- 8532927
TI  - [Strategies for the prevention of human immunodeficiency virus infection].

PMID- 8532928
TI  - [The rapid and slow progression of HIV infection].

PMID- 8532929
TI  - [Sinking of the cranial vault and headache].

PMID- 8532930
TI  - [Recurrent subcutaneous tumors in a woman from Equatorial Guinea].

PMID- 8532931
TI  - [Dermatitis and neurological changes].

PMID- 8532932
TI  - [An acute confusional picture in a previously healthy 52-year-old woman].

PMID- 8532933
TI  - [Cutaneous lesions and lung infiltrates after a trip to Thailand].

PMID- 8532934
TI  - [Retroperitoneal cystic masses associated with an elevation of serum amylase].

PMID- 8532935
TI  - [A 27-year-old woman with abdominal pain, vomiting, dark urine and hyponatremia].

PMID- 8532936
TI  - [Insulin-dependent diabetes mellitus and a malignant pheochromocytoma with a long
      term evolution].

PMID- 8532937
TI  - [The prescription of domiciliary oxygen therapy in patients with neoplastic
      diseases].

PMID- 8532938
TI  - [Leukocytoclastic vasculitis in relation to amlodipine administration].

PMID- 8532939
TI  - [The lessons from clinical trials in congestive heart failure].
AB  - During the last years, our knowledge on the pathophysiology and therapy of
      congestive heart failure has experienced a great growth. The goals of the therapy
      for heart failure have changed since new drugs have demonstrated to increase
      survival as well as to improve symptoms and functional capacity in patients with
      this syndrome. It has also been shown that therapeutic intervention can prevent
      the development of heart failure and decrease long-term mortality in patients
      with asymptomatic left ventricular dysfunction. In this article, we have reviewed
      the results from the most important clinical trials carried out during the last
      years in patients with overt congestive heart failure and asymptomatic left
      ventricular dysfunction with several drugs (digitalis, diuretics, angiotension
      converting-enzyme inhibitors, other vasodilators, calcium-antagonists, non
      glycoside inotropics antiarrhythmics, etc.). Nevertheless, in spite of this
      impressive increase in the knowledge on heart failure, some important questions
      remain unanswered.

PMID- 8532940
TI  - [The current status of the prevention and treatment of sudden death].
AB  - Sudden cardiac death is a major medical problem. The techniques to identify high
      risk patients have a limited value. Only betablockers, and perhaps amiodarone,
      are useful for primary prevention of sudden cardiac death. Prospective studies
      being carried out today with implantable cardioverter-defibrillator, will show us
      if these are the best way of treatment (secondary prevention) of sudden cardiac
      death.

PMID- 8532941
TI  - [The automatic, beat-to-beat determination of the QT interval and analysis of its
      spontaneous variability under basal conditions].
AB  - OBJECTIVES: An analysis is made of the automatic beat-by-beat measurement of QT
      and other intervals related to ventricular repolarization. The variability
      pattern of these intervals is investigated in normal subjects at rest, along with
      their relation to RR cycle variability. MATERIAL AND METHODS: The
      electrocardiographic signals (LII) from 11 normal subjects (mean age 31 +/- 10
      years) were recorded over 5 min and processed by applying specific algorithms to
      determine beat-by-beat the RR, QT, RT, QTm and RTm intervals (Tm = peak of T
      wave). An analysis was made of the variability of these intervals in the time
      (standard deviation, variation coefficient, difference between maximum and
      minimum values) and frequency domains (spectral analysis applying the Fourier
      transform). RESULTS: The differences between the automatic measurements and those
      performed by two observers (n = 110) were respectively -1.3 +/- 6.4 and -3.7 +/-
      6.5 ms for QT, - 1.0 +/- 1.4 and -1.0 +/- 2.3 ms for QTm, -0.3 +/- 1.4 and -0.2
      +/- 1.8 ms for RTm, and 0.7 +/- 6.5 and -2.8 +/- 10.3 ms for RT. The QT and RT
      intervals exhibited greater variability (SD = 6 +/- 1 ms) than QTm and RTm (SD =
      3 +/- 1 ms, p < 0.0001). These differences persisted on comparing the
      corresponding variation coefficients. The differences between the maximum and
      minimum measurements were 45 +/- 24 ms for QT and RT, the values being
      significantly less in the case of QTm (21 +/- 26 ms, p < 0.05) and RTm (20 +/- 27
      ms, p < 0.05). In the frequency domain, the high- (HF) and low-frequency (LF)
      band energies were low in the series formed by the ventricular repolarization
      intervals, and the LF band normalized amplitude was significantly lower than in
      the RR series. There were no significant differences in the frequencies of the
      maximum values of the LF and HF bands of the RR series with respect to the QT
      series. The correlations between the RR intervals and the subsequent
      repolarization intervals obtained in each subject were not significant in 7 of
      the 11 subjects studied. CONCLUSIONS: The automatic beat-by-beat determination of
      the ventricular repolarization intervals is precise, particularly when
      considering the intervals defined by the T wave peak. Repolarization variability
      during the sinus rhythm at rest is small, and is not linearly related to
      modifications of the previous RR interval. Neurovegetative and humoral influences
      are postulated to explain QT variations. The neurovegetative and humoral
      influences that regulate cardiac cycle and ventricular repolarization variability
      at rest, are found to be quantitatively different.

PMID- 8532942
TI  - [A method for the predictive estimation of the surgical risk in adult cardiac
      pathology].
AB  - INTRODUCTION: In order to test the efficiency of statistical predictive models,
      we compare the results of a standard method (Parsonnet) with the model created
      through the data of our population. MATERIAL AND METHODS: We used the chi 2
      univariate model, lineal and logistic regression with the data of the whole
      population receiving cardiac surgical procedure from January 1, 1990 to December
      31, 1993 (total 1626 patients). The population was divided into a control group
      (1100 cases, 68%) and a study group (526 cases, 32%). The coefficients of the
      control group were used to estimate the results in the study group. RESULTS:
      Univariate model p value. Significant (p < 0.001) for emergency, age, pulmonary
      hypertension, left ventricular failure, preoperative use of intra-aortic balloon
      pump; p < 0.05 mitral valve disease, aortic aneurysm and reoperation. No
      significance (p < 0.01) was found for gender, aortic or tricuspid disease,
      percutaneous transluminal coronary angioplasty, unstable or postinfarction
      angina, transplant, left main or vessel disease number, and mitral, tricuspid or
      aortic procedure. MULTIVARIATE MODEL: Emergency, pulmonary hypertension, age,
      left ventricular dysfunction and aortic aneurysm. We estimated a 5.2%, 5.2% and
      11.4% mortality with linear, logistic and Parsonnet method respectively with a
      real group mortality of 6.5%. The average error of the observed and predicted
      mortality after risk stratification was 5.7%, 6% and 12%. CONCLUSION: A model for
      risk prediction based on the data of the own institution is more accurate for
      that population than a model created for comparison between institutions, because
      the former takes account of the center and population peculiarities.

PMID- 8532943
TI  - [The effect of gallopamil and propranolol in patients with ischemic cardiopathy
      and moderate depression of ventricular function].
AB  - BACKGROUND: Calcium channel blockers have been wide and successfully used in the
      treatment of coronary heart disease. Gallopamil, a metoxylic derivative of
      verapamil, has many of its properties and so, caution is recommended when given
      to patients with depressed left ventricular function. Clinical studies about this
      effect are scarce, and we have assessed it in patients with coronary heart
      disease and diminished left ventricular function. METHODS: We studied 20 patients
      in a cross-over, randomized, double-blind study during three weeks active periods
      with two intercalating washout placebo periods of one week. Patients had history
      of previous myocardial infarction, positive exercise stress test and ejection
      fraction ranging from 30% to 50% by echocardiography. RESULTS: There were no
      significant differences between each drug and corresponding placebo on either
      systolic or diastolic function. When we compared both drugs, patients showed a
      milder increase in area under E after propranolol than after gallopamil (p <
      0.008). Clinical episodes of cardiac failure were not reported, and ejection
      fraction did not change. CONCLUSIONS: Both gallopamil and propranolol can be used
      in patients with coronary heart disease and moderately depressed left ventricular
      ejection fraction.

PMID- 8532944
TI  - [A comparative study of the efficacy of lisinopril versus quinapril in
      controlling light to moderate arterial hypertension. A follow-up with ABPM].
AB  - OBJECTIVE: To compare the antihypertensive efficacy of lisinopril versus
      quinapril given 20 mg once daily for the treatment of mild to moderate arterial
      hypertension (I-II WHO grades) using ambulatory blood pressure monitoring. This
      study also investigated the tolerance, adverse effects and changes in
      haematological or biochemical parameters with both drugs. METHODS: Fifty patients
      (men and women) with a range of age between 18 to 75 years were included in this
      open, randomized study to assess the hypotensive efficacy of lisinopril versus
      quinapril after 2 months of treatment, using ambulatory blood pressure monitoring
      (ABPM). To study data obtained from ABPM Mc Call curves were used and statistical
      analysis was made using Epistat programme. Covariance and Chi-square test were
      used for the comparative analysis of different variables, considering as
      statistically significant the value p < 0.05. Graphics were made using Lotus 123,
      V 3.0 version. All patients gave their informed consent to participate in the
      study. The protocol was approved by the Ethical Committee of the Clinico
      Hospital. RESULTS: Systolic blood pressure decreased from 172.6 to 152.6 mmHg in
      the lisinopril group (p < 0.001) and from 171.6 to 147 mmHg in the quinapril
      group (p < 0.001). Diastolic blood pressure decreased from 105.6 to 86.8 mmHg in
      the lisinopril group (p < 0.001) and from 106.1 to 88.1 mmHg in the quinapril
      group (p < 0.05). Using ABPM mean systolic blood pressure decreased from 157.3 to
      126.5 mmHg with lisinopril (p < 0.001) and from 148 to 137.4 mmHg with quinapril
      (p < 0.05). Mean diastolic blood pressure decreased from 93.6 to 81.7 mmHg with
      lisinopril (p < 0.001) and from 89.4 to 85.9 with quinapril (p < 0.05). Decreases
      in basal glycemia were found from 0.996 to 0.878 in quinapril group (p < 0.05),
      total quinapril cholesterol in both groups (from 228.7 to 207.2 with lisinopril
      and from 247.4 to 225.7 with quinapril) (p < 0.05) and cholesterol-LDL in the
      quinapril group (180.1 to 152.1) (p < 0.05). CONCLUSIONS: Both drugs produce a
      fall of blood pressure in mild-to-moderate hypertension, although using ABPM this
      fall is more significant with Lisinopril. According to Mc Call index 73.4% of
      patients in the lisinopril group and 62.7% of quinapril group controlled their
      hypertension, and a difference found between BP values obtained in the clinic and
      those obtained using ABPM.

PMID- 8532945
TI  - [Myocardiopathies (III). The classification and morphological patterns of
      hypertrophic myocardiopathy].
AB  - Hypertrophic cardiomyopathy is characterized by a great variety of clinical
      manifestations and morphologic patterns. Hemodynamic classification in
      obstructive and nonobstructive forms may be clinically relevant since, although
      many patients have disabling symptoms in the absence of a pressure gradient, in
      the subset of patients who do have a gradient, symptom severity seems to relate
      its magnitude; this fact supports the use of some therapeutic approaches directed
      to reduce or eliminate obstruction. Nevertheless, the presence and severity of
      the gradient do not correlate with prognosis. On the other hand, from a
      morphological point of view, any classification will be limited by the great
      diversity of morphologic patterns, which include almost all forms of ventricular
      hypertrophy one could imagine, and by the possibility of significant changes in
      the severity and distribution of the hypertrophy during the life of the patient.
      In general, the degree and distribution of ventricular hypertrophy do not
      correlate with symptoms or prognosis. The identification of different molecular
      genetic abnormalities responsible for the development of hypertrophic
      cardiomyopathy, is expected to provide new insights in the etiology and
      pathogenesis of this disease, which should be considered in future
      classifications.

PMID- 8532947
TI  - [Recurrent pericarditis: our experience with colchicine].
AB  - To prove the efficacy of colchicine in the prevention of recurrences of acute
      pericarditis, 5 patients, age 24 to 64 years (mean 36), were treated during 18
      months with 1 milligram daily. Previous treatment with steroids and/or non
      steroid antiinflammatory agents did not prevent 2-3 recurrences per patient, and
      was discontinued after entry into the study. There where no further recurrences
      of acute pericardial episodes during the 24 months of follow-up, and no side
      effects related to the treatment with colchicine were reported. We conclude that
      colchicine is effective in preventing the recurrences of acute idiopathic
      pericarditis.

PMID- 8532946
TI  - [Ventricular tachycardia secondary to phenylpropanolamine poisoning: apropos a
      case].
AB  - We report a case of a 17-years-old patient with an accidental ingestion of high
      doses of phenylpropanolamine. Nine hours after the ingestion she presented
      ventricular bigeminy and an episode of non sustained ventricular tachycardia. No
      cardiovascular disease was demonstrated.

PMID- 8532948
TI  - [Apical hypertrophic myocardiopathy and multiple fistulae between the coronary
      vessels and the left ventricle].
AB  - A male patient presented with symptoms of angor under effort. Echocardiography
      and angiocardiography revealed apical hypertrophic myocardiopathy, associated
      with multiple fistulas connecting the anterior descending coronary artery and
      right coronary artery with the cavity of the left ventricle, as demonstrated by
      coronariography. We comment on the hypothesis that support a causal relationship
      between the two anomalies, microfistulas being the possible cause of the reactive
      hypertrophy through the induction of a coronary steal phenomenon with local
      ischemia; alternatively, the myocardiopathy itself might be the cause of
      microfistulas formation by inducing an anomaly in the Thebesius venous system. A
      pathogenic relationship is suggested between the syndrome of angor and these two
      rare pathological entities.

PMID- 8532949
TI  - HDL-cholesterol increase associated to triglycerides degradation in vitro.
AB  - The effect of muscle tissue from rats trained by swimming on the extracellular
      degradation of triglyceride (TG) rich particles has been studied in vitro. During
      incubation, there is a progressive decline of the TG concentration in the
      incubation medium. At the end of the incubation period (90 min), a significantly
      reduction in the TG levels (p < 0.05) is associated with a significant increase
      in the high-density lipoprotein (HDL) cholesterol level (p < 0.005). There are no
      significant changes in total cholesterol levels. The correlation of the TG
      decline with the HDL-cholesterol increase is significant (r = 0.695, p < 0.05, n
      = 25). The experimental model used here could be of great interest for the in
      vitro study of factors affecting lipid levels in plasma.

PMID- 8532951
TI  - Blood parameter and heart rate response to training in Andalusian horses.
AB  - A study was performed on Andalusian horses in order to assess the response of
      heart rate and various blood parameters to training. Two tests were performed, at
      two and four months of training respectively. Exercise schedules were of
      increasing intensity, over a distance of 1000 meters. Speed was progressively
      increased, from 4 m/s to 8.5 m/s, over four exercise stages. In both tests, a
      recovery period of 5 min followed each stage. Sample collection (by puncture of
      the external jugular vein) was performed with the animals at rest, within the
      first minute after each exercise stage, and at 10, 15, 20 and 30 min of final
      recovery. Samples for analysis contained plasma for measurement of lactate,
      glucose, ion and creatinine levels. Heart rate was measured using the Polar Sport
      tester. The most important parameters in both tests proved to be glucose level,
      heart rate and lactate concentration. Variations in electrolyte and creatinine
      levels were transitory, normal resting values being regained after 30 minutes'
      recovery. Response to daily training was most clearly reflected in altered
      lactate levels and heart rate; recovery improved with increased training which
      enhanced aerobic capacity and decreased metabolic acidosis.

PMID- 8532950
TI  - Circadian rhythms of the salivary proliferation markers CA130 and CA125 in
      clinical health.

PMID- 8532952
TI  - Changes in the fatty acid pattern of plasma fractions of rats fed coconut, olive
      or sunflower oil.
AB  - The fatty acid composition of plasma phospholipids, triacylglycerols and
      cholesteryl esters from rats fed diets supplemented (10% w/v) with coconut, olive
      or sunflower oil during six days has been studied. Rats fed the olive oil diet
      showed an increased amount of oleic acid whereas the animals fed the sunflower
      oil diet showed a higher content of linoleic acid than that of the other two
      groups. n-6 polyunsaturated fatty acids were mainly carried in phospholipid and
      cholesteryl-ester fractions. There were no differences in the amount of n-6 and n
      3 polyunsaturated fatty acids. The effect of diet supplementation was shown after
      only six days of treatment and the results were similar to those reported in
      longer treatments.

PMID- 8532953
TI  - Alterations in food intake and thyroid tissue content by corticotropin-releasing
      factor in Tinca tinca.
AB  - The present experiments test the effects of intracerebroventricular injections of
      ovine corticotropin-releasing factor (1 microgram) on food intake, plasma glucose
      levels and thyroid function at 8 h postinjection in tench. Food intake and
      thyroid triiodothyronine (T3) content were significantly decreased after CRF
      treatment. Thyroid thyroxine (T4) content and plasma glucose levels were not
      modified by this neuropeptide. The present results suggest that CRF plays a role
      on food intake regulation and thyroid gland activity in tench.

PMID- 8532954
TI  - Influence of growth factors on the time-dependent meiotic progression of the
      bovine oocytes during their in vitro maturation.
AB  - The present study examines the effects of epidermal growth factor (EGF), insulin
      like growth factor-I (IGF-I), and the presence of cumulus cells on the meiotic
      progression of the bovine oocyte maturation. Oocytes were aspirated from 2-8 mm
      ovarian follicles, and the cumulus-oocyte complexes (COC) obtained (n = 2,729)
      were divided into COC or denuded oocytes. They were then cultured in four defined
      treatments comprising TCM-199 and growth-factors: control (no growth factor), IGF
      I, EGF, and EGF+IGF-I. Each treatment group of oocytes was cultured during 6, 12,
      18, 24, and 30 h; the oocytes were fixed and stained at the end of each 6 hour
      interval from 0 to 30-h, and were assessed for their nuclear maturation stage.
      Germinal vesicle (GV) and metaphase II (MII) stages present were used as the
      final parameters for data analysis. The results indicate that treatments with
      growth factors enhanced the incidence of GV activation and MII stage in all the
      culture periods. Maximal stimulation for nuclear maturation occurred with EGF+IGF
      I. As regards the denuded oocytes, no positive effects on nuclear maturation
      rates were observed for any treatment. These results suggest that EGF and IGF-I,
      singly and combined, stimulate the meiotic progression significantly, and this
      effect can be induced by a positive signal which is transferred from cumulus
      cells to oocyte.

PMID- 8532956
TI  - HCO3(-)-ATPase and Ca2+ dependent ATPase activities in the gills of the rainbow
      trout after the transfer to brackishwater and seawater.
AB  - The effect of seawater and brackishwater exposure on gill HCO3(-)-ATPase and Ca2+
      dependent ATPase activity in rainbow trout (Oncorhynchus mykiss) was investigated
      at different periods of time. HCO3(-)-ATPase activity decreased after the
      transfer to either brackishwater or seawater. Ca2+ dependent ATPase activity
      decreased during the initial period (1 to 4 days) in both salinities and
      recovered freshwater values from the 7th day onwards. No effect from fish size
      was detected in both parameters after saltwater transfer. The results are
      discussed in terms of salinity and long-term saltwater adaptation.

PMID- 8532955
TI  - One day estrous cycle shortening induced by antiprogestagen RU486 administration
      in proestrus to 4-day cyclic rats.
AB  - Administration of 4 mg of the antiprogestagen RU486 to 4-day cyclic rats in
      proestrus, which blocks proestrous and diestrous progesterone actions, induced a
      one day shortening of the ovarian cycle and a reduction of the ovulation rate in
      the following cycle. These effects were not present when RU486 was administered
      in estrus or metestrus. RU486 injections either in proestrus or estrus increased
      the serum levels of LH and 17 beta-estradiol during metestrus. However, only rats
      injected with RU486 in proestrus presented a 24 hour advancement of the
      preovulatory surge of gonadotropins and a lack of the LH-inhibiting effect of
      exogenous estradiol. These results suggest that, in 4-day cyclic rats, the
      secretion of progesterone by the corpora lutea during diestrous phase retards the
      follicular development by lowering the serum concentrations of LH, whereas
      progesterone secretion by the preovulatory follicles in proestrus regulates the
      estrous cycle length by antagonizing the desensitization of the pituitary to the
      estrogen negative feedback on LH secretion.

PMID- 8532957
TI  - Type 1-like helper T cell lines responsive to autologous peripheral blood
      monocytes established from two patients with sarcoidosis.
AB  - In the present study, T cell lines, designated TU/BAL and KC/LN, were established
      from bronchoalveolar lavage (BAL) fluid and an affected lymph node, respectively,
      obtained from patients with active sarcoidosis by cultivating in the presence of
      IL-2. These cell lines produced IL-2 and proliferated by stimulation with the
      patient's own peripheral blood mononuclear cells treated with mitomycin C, while
      three other T cell lines established from ConA-stimulated BAL cells of patients
      with non-sarcoid lung diseases did not show any proliferative responses. The
      proliferation was mediated by IL-2, because anti-IL-2R alpha-chain monoclonal
      antibody (mAb) inhibited this response in a dose-dependent fashion. The adherent
      cell was a main stimulator of the proliferation. Both CD4 and HLA-DR appeared to
      be involved, because mAbs against these molecules inhibited this response. These
      results suggest that T cells obtained from sarcoid patients respond to a certain
      unknown antigen associated with HLA-DR or some self antigen expressed on the
      monocytes. Furthermore, both TU/BAL and KN/LN represented a profile of Th1-like
      cells: they secreted IL-2 and IFN-gamma, but not IL-4, IL-5 and IL-6, when
      stimulated with PHA in the presence or absence of 12-O-tetradecanoylphorbol-13
      acetate. Thus, Th1-like cells activated by some unknown antigen(s) might play
      roles in the pathogenesis of sarcoidosis.

PMID- 8532958
TI  - Endothelin-1 excretion in urine in active pulmonary sarcoidosis and in other
      interstitial lung diseases.
AB  - Endothelin-1 (ET-1) is a vasoactive, mitogenic peptide that is variably increased
      in Bronchoalveolar Lavage Fluid (BALF) and immunohistochemically found in lung
      tissue of patients with Interstitial Lung Disease (ILD). To assess if endogenous
      ET-1 production is increased in ILD we evaluated 24 hour (24h) urine excretion of
      ET-1 in 20 patients with ILD and 10 healthy age-matched controls (HC). Eight
      patients with active pulmonary sarcoidosis (S), 6 with idiopathic pulmonary
      fibrosis (IPF) and 6 with focal lung fibrosis due to inactive pulmonary
      tuberculosis (hTB) were studied. Plasma ET-1 levels (ET-1pl, pg/ml) and 24h ET-1
      levels in urine (ET-1ur, ng/24h) were measured by a specific radio-immunoassay.
      Determinations of ET-1p1 and ET-1ur were repeated in S and IPF patients after 30
      days of prednisone (0.75 mg/kg/day) treatment. ET-1p1 concentrations were not
      different between HC (5.34 +/- 0.48), S (5.95 +/- 0.96), IPF (4.75 +/- 1.37) and
      hTB (5.97 +/- 1.05) groups. ET-1ur was significantly higher in S (189.50 +/-
      60.57) than in HC (69.00 +/- 10.76), IPF (62.17 +/- 19.07) and hTB (82.00 +/-
      24.97). After prednisone, ET-1ur in the S group decreased significantly (189.50
      +/- 60.57 to 94.00 +/- 13.60), and the decrease paralleled the improved clinical
      status. In S patients, ET-1ur was not significantly correlated to the degree of
      respiratory impairment, but it was significantly correlated to the intensity of
      lymphocytic alveolitis (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532959
TI  - Antibodies to heat shock proteins in patients with pulmonary sarcoidosis.
AB  - Serum concentrations of IgG, IgA, and IgM antibodies to three heat shock proteins
      (HSPs)--ubiquitin, HSP70, and HSP90--were measured using ELISA in 37 patients
      with pulmonary sarcoidosis. When compared to healthy controls (n = 44), increased
      concentrations of IgA and IgG antibodies to ubiquitin were found in 13 (35.1%, p
      < 0.002) and 7 (18.9%, p < 0.05) patients, respectively. In 10 patients (27.0%)
      elevated concentrations of IgG antibodies to HSP70 were detected (p < 0.02),
      whereas IgA antibodies to this protein were found in 7 cases (18.9%, p < 0.05).
      IgM antibodies to ubiquitin and HSP70, and antibodies to HSP90 were not detected
      in patients' sera. The levels of antibodies to ubiquitin and HSP70 correlated
      well with each other within the given immunoglobulin class (r = 0.7391, p < 1E-5
      and r = 0.9854, p < 1E-5 for IgG and IgA class, respectively). There was also a
      weak correlation between the level of IgG antibodies to HSP70 and both serum
      activity of angiotensin converting enzyme (SACE; r = 0.4668, p < 0.005) and serum
      level of soluble receptor for interleukin 2 (sIL-2-R; r = 0.4142), p < 0.02). A
      similar tendency was seen with IgG antibodies to ubiquitin. Furthermore, there
      was an association between the increased concentration of C-reactive protein
      (CRP) and increased levels of IgG antibodies to ubiquitin and HSP70 (p < 0.005
      and p < 0.05, respectively). Our results suggest that antibodies to various HSPs
      are present in a subset of patients with sarcoidosis. The humoral immune response
      to HSPs relates probably to the immune activation and/or infection.

PMID- 8532960
TI  - Splenomegaly in sarcoidosis: a report of 16 cases.
AB  - The reported frequency of splenomegaly in sarcoidosis has ranged from 1% to 40%.
      Splenomegaly has been associated with clinical evidence of more extensive
      extrathoracic sarcoidosis. In a previous study, we reported that splenomegaly was
      associated with a poor outcome of the disease. The aim of the present study was
      to describe the characteristics of the sarcoidosis patients with splenomegaly
      seen at our institution. Of 284 sarcoidosis patients, followed up at our
      hospital, 16 (5.6%) had splenomegaly on physical examination. These patients
      showed other extrathoracic manifestations as well, and all but two showed
      intrathoracic involvement. Eleven patients received corticosteroid therapy.
      Splenectomy was done in three patients, but the natural history of their
      sarcoidosis remained unaltered two years after diagnosis. The results of this
      study disclosed that patients with splenomegaly had evidence of extensive
      pulmonary and extrathoracic sarcoidosis with a poor prognosis in spite of steroid
      therapy.

PMID- 8532961
TI  - Activation of bronchoalveolar lavage T lymphocytes and clinical, functional and
      radiological features in sarcoidosis.
AB  - Previous studies on the relationship between activated BAL T lymphocytes and
      clinical features in sarcoidosis revealed controversial results. We determined
      lavage lymphocytes, T lymphocytes, activated T lymphocytes, helper, suppressor
      and natural killer cells in 50 patients with pulmonary sarcoidosis and compared
      the results with clinical findings, serum angiotensin converting enzyme (ACE),
      the radiological pattern and lung function data (vital capacity [VC], total lung
      capacity [TLC], FEV1, transfer coefficient KCO and arterial-alveolar oxygen
      difference [AaDO2] during exercise). Patients with erythema nodosum (n = 7)
      showed a lower proportion of activated T lymphocytes (p < 0.05) and lymphocytes
      (p < 0.01) than the other patients. There was a significant correlation between
      activated T lymphocytes and AaDO2 during exercise (r = 0.49, p < 0.001), and an
      inverse correlation was seen between activated T lymphocytes and VC or TLC (r = 
      0.35 and r = -0.36, p < 0.01). We conclude that the percentage of activated BAL T
      cells may be related to the degree of parenchymal involvement as expressed by
      functional disturbance.

PMID- 8532962
TI  - Sarcoidosis following beta-interferon therapy for multiple myeloma.
AB  - Some reports correlate the administration of all forms of interferon with the
      development or exacerbation of autoimmune phenomena and diseases, including
      sarcoidosis, because of the strong and complex immune action of interferons. We
      report on a case of sarcoidosis following beta-interferon treatment for multiple
      myeloma. Differently from what had been observed in all the 8 previously reported
      cases of associated multiple myeloma and sarcoidosis, where the plasmacellular
      malignancy followed the onset of the respiratory disease, in the case of our
      patient, sarcoidosis arose after multiple myeloma was first diagnosed.

PMID- 8532963
TI  - Mucormycosis in a patient with sarcoidosis.
AB  - Mucormycosis is a rare complication of sarcoidosis. We report only the third
      instance of mucormycosis occurring in a patient with sarcoidosis. Corticosteroid
      therapy, even short courses of less than one month duration, appears to be a
      major risk factor for the development of mucormycosis. Mucormycosis should be
      suspected upon the development of signs and symptoms of chronic sinusitis,
      necrotic nasal discharge, proptosis or periorbital edema. Mucormycosis is
      confirmed on routine hematoxylin and eosin stains by the identification of tissue
      invasion by the broad, aseptate mucor fungi. Prompt identification of the
      infection is essential to reduce morbidity and prevent mortality.

PMID- 8532965
TI  - Japan Society of Sarcoidosis 14th annual meeting. Hiroshima, October 20-21, 1994.
      Abstracts.

PMID- 8532964
TI  - Increase of serum copper concentration in Lofgren syndrome.
AB  - Chest X ray showing bilateral hilar adenopathies of the mediastinum associated
      with erythema nodosum suggests the diagnosis of Lofgren syndrome rather than the
      presence of a lymphoproliferative disorder. However, the occasional finding of
      high serum levels of copper can induce diagnostic doubts since serum copper
      increase is an index of lymphoproliferative disorders, particularly of Hodgkin's
      disease. We observed four patients with Lofgren syndrome presenting with fever,
      arthralgies, bilateral hilar adenopathies of the mediastinum and erythema
      nodosum. All patients underwent whole staging for sarcoidosis and serum copper
      levels were measured. In all cases clinical and instrumental data allowed the
      diagnosis of sarcoidosis and in all the patients we found high levels of serum
      copper with an average of 34.8 mumol/L (30.7-39.4) at the onset of the disease.
      Three months later, the sarcoid process spontaneously remitted and the serum
      copper levels returned to normal range. Although the finding of an increase of
      serum copper in patients with mediastinal adenopathies is usually indicative of a
      lymphoproliferative disorder (Hodgkin's disease), our data suggest that its
      increase can be related also to non neoplastic adenopathies of the mediastinum,
      including sarcoidosis.

PMID- 8532966
TI  - Granuloma formation signifies a Th1 cell profile.

PMID- 8532967
TI  - Non-sarcoid granulomatous disease with involvement of the lungs.
AB  - Pulmonary granulomatous disease can severely damage the lungs and represents a
      rather uniform response of the lungs to a multitude of different stimuli.
      Histologically, granulomatas can be broadly classified as either hypersensitivity
      type or foreign-body-type. A wide variety of infectious and non-infectious
      etiologies discussed in this review have been identified as causes of
      granulomatous inflammation of the lungs. An infectious origin should always be
      excluded since specific etiologic therapy may be implemented. Culture techniques
      for microorganisms or fungi and standard or special stains of tissue samples are
      crucial to establish the specific etiologies. The mechanisms leading to granuloma
      formation are still poorly understood, but the role of parenchymal cells,
      fibroblasts, endothelial and epithelial cells, and cytokines, has been better
      appreciated; all of them are important in the initiation, maintenance, and
      resolution of the lesion. Whether these new insights will finally lead to new
      ways of treating lung granuloma remains to be determined.

PMID- 8532968
TI  - Principles of radiation therapy.
AB  - Radiation therapy can provide long-term control of local or locoregional cancer
      without removal of large volumes of tissue and with preservation of function of
      surrounding normal tissues. Radiation therapy is used for cancers that have
      extended near or around critical structures such as spinal cord, nerves, or large
      vessels. Normal tissue response limits the total radiation dose that can be used.
      The objective of radiation therapy is to provide the highest probability for
      local tumor control with a probability for serious complications such as bone or
      soft-tissue necrosis of less than 5%. Radiation therapy can be used in
      combination with surgery and/or chemotherapy; however, there should be a
      carefully coordinated treatment plan. The basic principle of cancer treatment
      with curative intent is to treat as early and as aggressively as possible. The
      first opportunity for tumor control is always the best opportunity. Radiation
      oncologists are using improved equipment and greater knowledge of radiation
      biology to maximize tumor control and to minimize normal tissue injury.
      Currently, most veterinary radiation oncology practices use an external beam
      source of radiation from either cobalt 60 teletherapy units or clinical
      accelerators. Many practices use daily treatments for 3 to 4 weeks. The
      relatively short overall treatment time prevents significant repopulation of
      tumor cells during the course of treatment. The total dose is divided into
      several smaller fractional doses that spares late responding normal tissues.

PMID- 8532969
TI  - Physics and treatment planning.
AB  - Small changes in delivered radiation dose may have a dramatic effect on the
      probability of treatment success or complications. Also, radiation therapy is
      stressful for animal patients, and the treatment procedure results in the
      consumption of many resources making it expensive for the pet owner. Thus, it is
      critical that individuals administering radiation therapy to pets with cancer
      have a sound understanding of the basic physical principles of matter and
      ionizing radiation, as well as an appreciation for the nuances of treatment
      planning. In this article, these topics are reviewed and illustrations are
      provided to aid in the understanding of important principles.

PMID- 8532970
TI  - Tumor physiology and cell kinetics.
AB  - The abnormal physiological state of tumors has traditionally been thought to be a
      source of treatment resistance and altered metastatic phenotype. However, the
      recent recognition that this altered physiological state is unique to solid
      cancers gives some hope that tumor selective therapeutic strategies could be
      developed that will specifically target these cells. Investigations into the
      development of drugs that specifically target acidotic and hypoxic cells could
      represent a significantly selective adjuvant therapy to be used in combination
      with more traditional forms of treatment. Newer forms of targeted therapy will
      rely on delivery of directed antibodies, growth factor receptor ligands, or gene
      therapy, delivered via immune cells or viruses. Unfortunately, physiological
      barriers exist in tumors that will impede the success of such strategies no
      matter how specific they are. Methods to ameliorate high interstitial pressures
      and defects in adhesion molecule function are needed to circumvent these
      barriers. Current methods of evaluating tumor cell kinetics provide data quickly,
      so this information could impact treatment decisions. Kinetic parameters are
      proving to be useful tools in selecting patient subpopulations that may respond
      better to altered treatment regimens. Studies in spontaneous rodent and
      xenografted human tumors have shown that the number of clonogens per tumor and
      their intrinsic sensitivity to radiation are major determinants of radiation
      tumor control dose.

PMID- 8532971
TI  - Tumor diagnosis, grading, and staging.
AB  - Optimal use of radiation therapy for the treatment of animal tumors necessitates
      accurate clinical evaluation, diagnostic imaging, and pathology. This requires a
      coordinated effort between the clinical and radiation oncologist, radiologist,
      and pathologist. The histological appearance of the tumor, tumor grade, and tumor
      stage are important diagnostic criteria that need to be established. Diagnostic
      imaging, including radiographic, computerized tomographic, magnetic resonance
      imaging, and ultrasound studies are helpful in establishing an accurate tumor
      location and diagnosis. Biopsy and histological examination of tumor tissue are
      necessary for final diagnosis of tumor type. Determination of tumor type is
      critical because different tumor types vary in regard to radiosensitivity, local
      behavior, and propensity for regional and systemic metastasis. The histological
      grade of many tumors is an important indicator of the potential for local
      invasion or systemic metastases, and may influence treatment response. Tumor
      staging as determined by clinical evaluation, imaging studies, and histological
      evaluation is necessary to establish the extent of the tumor, both locally,
      regionally, and systemically. The clinical oncologist should have an
      understanding of the procedures involved in tumor diagnosis, tumor grading, and
      tumor staging. This provides a better understanding of the neoplastic condition
      and recognition of the limitations of diagnostic procedures. Tumor type, grade,
      and stage all impact radiation treatment planning and the need for adjuvant
      regional or systemic therapy.

PMID- 8532972
TI  - Radiation therapy for head and neck cancers.
AB  - Radiation therapy may be indicated for larger invasive tumors of the head and
      neck that may be difficult to surgically excise or for which surgery would be
      significantly disfiguring. Previous studies of oral squamous cell carcinomas
      indicate that it should be possible to control approximately 80% of all but the
      most advanced local or locoregional tumors. Aggressive radiation therapy to total
      doses of 56 Gy or greater may be required. That can be done by using smaller
      doses per fraction and gradually reducing the size of the field so that the
      highest dose is given only to the tumor with a relatively tight margin. Malignant
      melanomas can be controlled locally apparently with a few large fractions.
      Metastatic disease limits survival; therefore, some type of systemic therapy
      seems to be needed to improve survival of those patients. Canine oral
      fibrosarcomas require a very high dose for a reasonable probability of control.
      It seems that a dose of 56 Gy given in 3.3 Gy fractions might provide local
      control of 50% of the tumors. It is likely that a combination of surgery and
      radiation would significantly improve the probability for control. Oral squamous
      cell carcinomas of cats must also be treated very aggressively to improve local
      control. Tumors of the nasal cavity are usually very large and invasive at the
      time of diagnosis. Radiation therapy has been shown to be effective in some
      instances. It is possible that with better definition of the tumor through
      computerized tomography imaging and improved treatment planning, control of these
      difficult to manage nasal tumors can be improved.

PMID- 8532973
TI  - Soft-tissue sarcomas.
AB  - Canine and feline soft-tissue sarcomas are difficult to control with surgery
      unless aggressive procedures such as compartmental resection or amputation are
      performed. Additionally, multiple noncurative surgeries result in recurrent
      tumors that are difficult to control with other modalities. Little is known about
      the radiation response of soft-tissue sarcomas in animals, but available data
      suggest they are radioresistant. Various methods of improving radiation response
      of soft-tissue sarcomas have been evaluated. These include the combination of
      radiation with radioprotective agents, hyperthermia, and surgery. Of all methods
      evaluated to date the judicious combination of surgery and radiation seems to
      hold the most promise for producing permanent local control of a significant
      percentage of canine and feline sarcomas.

PMID- 8532974
TI  - Central nervous system tumors.
AB  - Central nervous system (CNS) tumors are relatively common in veterinary medicine,
      with most diagnoses occurring in the canine and feline species. Numerous tumor
      types from various cells or origins have been identified with the most common
      tumors being meningiomas and glial cell tumors. Radiation therapy is often used
      as an aid to control the clinical signs associated with these neoplasms. In
      general, these tumors have a very low metastatic potential, such that local
      control offers substantial benefit. Experience in veterinary radiation oncology
      would indicate that many patients benefit from radiation treatment. Current
      practice indicates the need for computed tomography or magnetic resonance imaging
      studies. These highly beneficial studies are used for diagnosis, treatment
      planning, and to monitor treatment response. Improvements in treatment planning
      and radiation delivered to the tumor, while sparing the normal tissues, should
      improve local control and decrease potential radiation related problems to the
      CNS. When possible, multiple fractions of 3 Gy or less should be used. The
      tolerance dose to the normal tissue with this fractionation schedule is 50 to 55
      Gy. The most common and serious complications of radiation for CNS tumors is
      delayed radiation myelopathy and necrosis. Medical management of the patient
      during radiation therapy requires careful attention to anesthetic protocols, and
      medications to reduce intracranial pressure that is often elevated in these
      patients. Canine brain tumors have served as an experimental model to test
      numerous new treatments. Increased availability of advanced imaging modalities
      has spawned increased detection of these neoplasms. Early detection of these
      tumors with appropriate aggressive therapy should prove beneficial to many
      patients.

PMID- 8532975
TI  - Radiation therapy of thoracic and abdominal tumors.
AB  - Until recently, radiotherapy of thoracic and abdominal tumors in animals has been
      limited. However, the availability of computerized tomography and other imaging
      techniques to aid in determining the extent of tumor, an increase in knowledge of
      dose tolerance of regional organs, the availability of isocentrically mounted
      megavoltage machines, and the willingness of patients to pursue more aggressive
      treatment is making radiation therapy of tumors in these regions far more common.
      Tumor remission has been reported after radiation therapy of thymomas. Radiation
      therapy has been used to treat mediastinal lymphoma refractory to chemotherapy,
      and may be beneficial as part of the initial treatment regimen for this disease.
      Chemodectomas are responsive to radiation therapy in human patients, and
      favorable response has also been reported in dogs. Although primary lung tumors
      in dogs are rare, in some cases radiation therapy could be a useful primary or
      adjunctive therapy. Lung is the dose-limiting organ in the thorax. Bladder and
      urethral tumors in dogs have been treated using intraoperative and external-beam
      radiation therapy combined with chemotherapy. These tumors are difficult to
      control locally with surgery alone, although the optimal method of combining
      treatment modalities has not been established. Local control of malignant
      perianal tumors is also difficult to achieve with surgery alone, and radiation
      therapy should be used. Intraoperative radiation therapy combined with external
      beam radiation therapy has been used for the management of metastatic carcinoma
      to the sublumbar lymph nodes. Tolerance of retroperitoneal tissues may be
      decreased by disease or surgical manipulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8532976
TI  - Combining radiation therapy with other treatment modalities.
AB  - Combining treatment modalities is indicated when single modality treatment does
      not result in adequate tumor control, or if the cosmetic or functional outcome of
      single modality treatment is less than desirable. The combination of surgery and
      radiation has proven useful in the treatment of both human and veterinary
      patients. Surgery can be used to remove large, bulky tumors whereas radiation
      therapy eliminates the subclinical disease adjacent to the tumor mass that
      invades important normal tissue structures. If properly combined, the result
      should be better tumor control combined with a better functional and cosmetic
      outcome. Radiation therapy can be administered preoperatively, postoperatively,
      and intraoperatively, depending on a variety of factors. Radiation therapy
      combined with hyperthermia has a strong scientific rationale. Hyperthermia is
      particularly effective against some cells, such as those in late S-phase, that
      are resistant to radiation therapy. Nutrient-deprived cells and cells with low pH
      are also very sensitive to hyperthermia, and these may reflect areas in a tumor
      where hypoxia may be present. Therapeutic gain has been shown in randomized
      clinical trials combining radiation therapy and hyperthermia in tumor bearing
      dogs. However, the disadvantage of hyperthermia for both human and veterinary
      tumors remains the inability to adequately maintain uniform temperatures to the
      tumors. Chemotherapy is an important adjuvant to radiation therapy for the
      control of distant tumor spread. The scientific rationale for combining
      chemotherapy with radiation therapy for local control is less clear, and is
      complex because of a variety of factors.

PMID- 8532977
TI  - Palliative radiation therapy.
AB  - Animal owners may be reluctant to have pets with incurable cancer subjected to
      euthanasia. Palliative radiation therapy may provide significant relief of pain
      in such pets. Palliative irradiation is comprised of a few radiation treatments,
      frequently given over a short time and using larger than normal fractional doses.
      Animals tolerate palliative irradiation well, and recent reports attest to the
      usefulness of palliative radiation to relieve discomfort associated with both
      skeletal and extraskeletal tumors. Although there is more to learn regarding the
      response of canine and feline tumors to palliative irradiation, it is a proven
      modality for relief of pain in many incurable cancer patients.

PMID- 8532979
TI  - An analysis for menstrual data with time-varying covariates.
AB  - This paper concerns the analysis of menstrual data; in particular, methodology to
      identify variables that contribute to the variability of menstrual cycles both
      within and between women. The basis for the proposed methodology is a
      parameterization of the mean length of a menstrual cycle conditional upon the
      past cycles and covariates. This approach accommodates the length-bias and
      censoring commonly found in menstrual data. Data from a longitudinal study of
      menstrual patterns and other variables among Lese women of the Ituri Forest,
      Zaire, illustrate the methodology. A small simulation illustrates the bias caused
      by incorrectly deleting the censored cycles.

PMID- 8532978
TI  - Normal tissue tolerance and management of radiation injury.
AB  - The objective of effective cancer therapy includes preservation of normal tissue
      function and reducing injury as much as possible. Acutely responding tissues such
      as skin and mucous membranes generally show a reaction during the course of
      radiation therapy. Normally those reactions heal rapidly after radiation therapy
      is completed. The short-term injury is justified if a reasonable probability of
      local tumor control is expected with an increase in survival of several months.
      Late effects are more challenging to manage and, therefore, the probability of
      occurrence is reduced by the methods of irradiation. If the tumor is located such
      that eyes or salivary glands are included in the field, the late effects include
      keratoconjunctivitis sicca and, less frequently, xerostomia. Those responses
      require continual observation and care by the animal owner. A goal in radiation
      therapy is to keep the incidence of serious complications such as bone or soft
      tissue necrosis below 5%. The incidence of complications of radiation therapy
      that have serious impact on quality of life or quality as a companion animal is
      probably much less than 5%.

PMID- 8532980
TI  - Modelling frailty in area mortality.
AB  - This paper investigates the impact on area life tables of the specification of
      unobserved frailty. Frailty specification may affect both the regression effects
      of area and individual level covariates, and lead to changes in the value of
      summary mortality parameters, such as life expectancy. The paper also
      investigates how frailty affects life tables for specific causes of death,
      especially lung cancer and heart disease. Implications for choice between
      different model specifications, both in terms of age dependence and frailty, are
      discussed. The focus is on registered deaths recorded by age, birthplace and by
      small area within a borough of Greater London.

PMID- 8532981
TI  - Simple confidence intervals for standardized rates based on the approximate
      bootstrap method.
AB  - This paper presents simple expressions for the confidence intervals of indirect
      and direct standardized rates, based on the approximate bootstrap confidence
      (ABC) method of DiCiccio and Efron. For indirect rates, the ABC method compares
      favourably with the exact methods. An exact method is not available for direct
      standardized rates. I, therefore, compared the ABC to other simple procedures for
      confidence intervals, namely: the standard normal, log-normal, and a recent
      method proposed by Dobson et al. Simulation studies of the coverage properties of
      these methods for direct standardized rates show that the ABC method performs
      best, with balanced tail probabilities close to their expected values.

PMID- 8532982
TI  - Difference in clinical implications of CD4 counts among HIV-infected homosexual
      men and injection drug using men and women.
AB  - While the relationship between CD4 counts and clinical symptoms is well
      established among homosexual men, the same is not true for injection drug using
      men and women (IDUM and IDUW). In this paper we investigate whether CD4 counts
      have the same clinical implications for IDUM and IDUW as for homosexual men. We
      estimated the CD4 counts at which 50 per cent of the HIV-infected but AIDS-free
      population has AIDS related complex (ARC) based on three biannually measured CD4
      counts. The analyses involve interval, right and left censored threshold data. We
      took the parametric approach, assuming that the threshold values for ARC arise
      from a family of distributions that includes symmetric, left or right skewed
      distributions, in which the logistic and extreme value distributions are embedded
      as special cases. The resulting estimates of median thresholds of CD4 counts for
      ARC were 249, 424 and 755 for homosexual men, IDUM, and IDUW, respectively. The
      results were robust with respect to the assumptions on the underlying
      distribution.

PMID- 8532983
TI  - Combining 2 x 2 tables that contain structural zeros.
AB  - When one cell or more of a contingency table is necessarily zero, the table is
      said to contain structural zeros. These structural voids may be inherent to the
      problem at hand, or, in some applications, they may be introduced intentionally
      through the experimental design. With data classified by a third stratification
      variable, one needs a method for analysing a set of independent 2 x 2 tables. We
      propose Cochran-Mantel-Haenszel type analyses that combine observations across
      strata. We also propose tests of hypotheses pertaining to the marginal and
      conditional probabilities.

PMID- 8532984
TI  - A multiple imputation strategy for clinical trials with truncation of patient
      data.
AB  - Clinical trials of drug treatments for psychiatric disorders commonly employ the
      parallel groups, placebo-controlled, repeated measure randomized comparison. When
      patients stop adhering to their originally assigned treatment, investigators
      often abandon data collection. Thus, non-adherence produces a monotone pattern of
      unit-level missing data, disabling the analysis by intent-to-treat. We propose an
      approach based on multiple imputation of the missing responses, using the
      approximate Bayesian bootstrap to draw ignorable repeated imputations from the
      posterior predictive distribution of the missing data, stratifying by a balancing
      score for the observed responses prior to withdrawal. We apply the method and
      some variations to data from a large randomized trial of treatments for panic
      disorder, and compare the results to those obtained by the original analysis that
      used the standard (endpoint) method.

PMID- 8532985
TI  - Toward vital status sweeps: a case history in sequential monitoring.
AB  - We use data from the Cardiac Arrhythmia Suppression Trial (CAST) to demonstrate
      the sensitivity of sequential monitoring to the timeliness of survival data. In
      CAST vital status sweeps were not routinely performed prior to the times of
      sequential analysis. Examination of the delay between death and reporting of
      death shows that the change in the time of sequential analysis by even as few as
      several months can have dramatic impact on the results of the sequential
      analysis.

PMID- 8532986
TI  - On the use of a pilot sample for sample size determination.
AB  - To compute the sample size needed to achieve the planned power for a t-test, one
      needs an estimate of the population standard deviation sigma. If one uses the
      sample standard deviation from a small pilot study as an estimate of sigma, it is
      quite likely that the actual power for the planned study will be less than the
      planned power. Monte Carlo simulations indicate that using a 100(1-gamma) per
      cent upper one-sided confidence limit on sigma will provide a sample size
      sufficient to achieve the planned power in at least 100(1-gamma) per cent of such
      trials.

PMID- 8532987
TI  - Additivity test for composition of binomial effects in chromosome aberrations
      after radiation injury.
AB  - Additivity of clastogenic effects of two doses of radiation to human peripheral
      blood lymphocytes is considered. We compare the effects of combined tritium and
      gamma irradiation with the sum of the effects of either irradiation administered
      separately. Our solution is based on combination of de Moivre and Cramer-Slucky
      theorems. The results for 14 subjects where the deletion types of chromosome
      aberrations were counted indicate a Normal distribution of the sample additivity
      index, oscillating non-significantly around zero, with one outlier towards
      adaptivity and another towards synergism of the effect of the two doses absorbed
      by the cells.

PMID- 8532988
TI  - [Pharma clinics: how I treat... Inflammatory intestinal diseases and pregnancy].

PMID- 8532989
TI  - [Clinical case of the month. Major depression in a diabetic patient].

PMID- 8532990
TI  - [Methotrexate in rheumatology: a therapeutic revolution].

PMID- 8532991
TI  - [Role of the general practitioner in screening for and diagnosis of breast
      cancer].

PMID- 8532992
TI  - [Therapeutic approach to epithelial cancer of the ovary at CHU Sart Tilman.
      Conclusions of the interdisciplinary meeting of 22 March 1995. Consensus Group].

PMID- 8532993
TI  - [Neurovascular facial pain].

PMID- 8532994
TI  - [Dermatoses and winter sports].

PMID- 8532995
TI  - [Nitric oxide. Current findings on the synthesis and genetics of nitric oxide
      synthases, regulation of hypothalamic and vascular function].

PMID- 8532996
TI  - [How I examine... anemia (2)].

PMID- 8532997
TI  - [Pharma clinics. Drug of the month. Acipimox (Olbetam)].

PMID- 8532998
TI  - [2nd European study on secondary prevention of stroke (ESPS 2). Respective roles
      of acetylsalicylic acid, dipyridamole and their combination].

PMID- 8532999
TI  - [Secondary effects of fluoroquinolones: experience of French drug monitoring].

PMID- 8533000
TI  - [The eye and HIV].

PMID- 8533001
TI  - [Causes and consequences of an unbalanced vaginal ecosystem].
AB  - The vaginal microflora of a healthy asymptomatic woman is part of a dynamic
      ecosystem which is easily disturbed by known and unknown factors. The normal
      vaginal microflora consists of a broad spectrum of aerobic and anaerobic germs.
      The anaerobic microaerophilic Doederlin's bacillus (lactobacillus) plays a major
      role in the microflora, but is only one of the many factors controlling and
      tuning a well-balanced ecosystem. Although our understanding is still
      insufficient, basic knowledge of the ecosystem and new results lead to a
      successful therapeutic approach.

PMID- 8533002
TI  - [Pathology and pathogenesis of extranodal lymphomas in the gastrointestinal
      tract].
AB  - Primary extranodal lymphomas of the stomach represent a fascinating object of
      investigation for clinicians and basic scientists. Possibly multifocal clonal
      populations of lymphocytes develop, which progress to highly malignant lymphomas
      over many years, starting from a previous reactive disease, commonly an
      Helicobacter-pylori-associated chronic gastritis or an organ related autoimmune
      disease in case of other sites of MALT lymphomas. In early stages of clonally
      restrained NHL of low malignancy of the MALT type a complete tumor regression can
      be achieved by elimination of the triggering agent Helicobacter pylori. At least
      a long standing remission is expected. The site and the frequency of relapse
      cannot be predicted until now. Basic requirement for the treatment by eradication
      of Helicobacter is the doubtless and well documented diagnosis of a low malignant
      NHL, based on immunohistological++ and molecular biologic findings, to prove
      scientifically the efficacy of this treatment. This will establish the basis to
      assess the stage and the grade of a primary gastric lymphoma in the future.

PMID- 8533003
TI  - [Primary non-Hodgkin lymphoma of the stomach--surgical aspects].
AB  - In each histological subtype of a primary gastric non-Hodgkin lymphoma laparotomy
      is performed with the intention of an R0 resection. This concept appears to be
      rather aggressive if you take into account the possibilities of the other
      treatment modalities; however, because of the diagnostic uncertainty and of the
      changing histologic classifications there is an uncertainty about the character
      and the dissemination of the tumor. Consequently total gastrectomy with
      systematic lymphadenectomy provides enough basic informations to plan multimodal
      therapeutic concepts and their clinical evaluations.

PMID- 8533004
TI  - [Primary non-Hodgkin lymphoma of the stomach--internal medicine aspects].
AB  - Primary gastric malignant non Hodgkin lymphomas occupy a special position, which
      is documented in the new histologic classification according to the MALT-concept.
      Our knowledge about the pathogenesis of this entity, its clinical and biologic
      behaviour and its morphologic and molecular biologic characteristics is
      increasing. Endosonography might be of outstanding value for the differentiation
      between the stages EI1, EI2 and EII1. The adequate treatment of these lymphomas
      is still under debate. Prospective multicenter studies were not performed. Our
      multicenter study has a stage adapted treatment schedule. We hope to answer some
      of the open questions.

PMID- 8533005
TI  - [Initial results of the HOT-study in Switzerland (hypertension optimal
      treatment)].
AB  - The HOT study (hypertension-optimal treatment) is an international clinical study
      on primary prevention of cardiovascular events in 19,193 hypertensive patients
      worldwide. It aims at the recognition of the optimal diastolic blood pressure
      value (< 90, < 85 or < 80 mmHg?) in order to maximize the possible benefit of an
      antihypertensive therapy. In addition, the HOT study investigates whether low
      doses of aspirin (75 mg/day) are able to reduce the occurrence of severe
      cardiovascular events. In Switzerland a total of 797 patients have been enrolled
      in the study. Antihypertensive therapy was initiated with felodipine = Plendil (5
      mg/day). This vasoelective calcium antagonist could reduce diastolic blood
      pressure values to < 90 or < 80 mg/Hg, respectively, in one of two or one of
      three patients within the first three months. In nine or six patients,
      respectively out of ten a reduction of diastolic blood pressure values to < 90 or
      < 80 mmHg was reached within one year by combination of felodipine with other
      antihypertensive drugs (ACE inhibitors, beta blockers and diuretics).

PMID- 8533006
TI  - [A case from practice (337). Psoriasis vulgaris, Hallopeau's continuous
      suppurative acrodermatitis. Psoriatic arthropathy. Chronic alcoholism with
      personality changes, polyneuropathy, hepatopathy. Cardiomyopathy with chronic
      atrial fibrillation, thrombocytopathy, macrocytosis].

PMID- 8533007
TI  - Protein thiol modification and apoptotic cell death as cGMP-independent nitric
      oxide (NO) signaling pathways.
AB  - Nitric oxide signaling is achieved through both cGMP-dependent and cGMP
      independent mechanisms. The latter are exemplified by protein thiol modification
      followed by subsequent NAD(+)-dependent automodification of the glycolytic enzyme
      GAPDH, or by mechanisms inducing accumulation of the tumor suppressor gene p53
      and causing apoptotic cell death. Both cGMP-independent actions are initiated
      using NO-releasing compounds and an active LPS/cytokine-inducible NO synthase. NO
      synthase inhibitors block the release of NO and hinder downstream signaling
      mechanisms; they are therefore valuable pharmacological tools linking a defined
      cellular response to various NO actions. Signal transducing mechanisms elicited
      by NO can be studied using GAPDH as a representative example of NO-induced
      protein modification and are grouped as follows: --S-Nitrosylation reactions
      initiated by NO+ --NAD(+)-dependent, post-translational covalent automodification
      of GAPDH --Oxidative modification (thiol oxidation) and inhibition of GAPDH by NO
      related agents, probably ONOO- GAPDH and several other protein targets may serve
      as molecular sensors of elevated NO concentrations and may transmit this message
      through posttranslational modification and oxidation-induced conformational
      changes as cGMP-independent NO signaling pathways. Toxicity of NO seems to be
      linked to both apoptosis and necrosis, depending on the chemistry of NO it
      undergoes in a given biological milieu. Toxicity manifests as a relative excess
      of NOx, metal-NO interactions, and ONOO- formation in relation to cellular
      defense systems. Although accumulation of the tumor-suppressor gene product p53
      in response to NO opens a regulatory mechanism known to be involved in apoptotic
      cell death, cGMP-independent signaling pathways remain to be elucidated. As NO
      dependent modification of GAPDH would imply down-regulation of glycolysis and
      concomitant energy production followed by cell death, our data so far do not
      support this assumption. In recent years, NO has proved to be a beneficial
      messenger with a potentially toxic activity. It will be challenging to
      investigate NO biochemistry in closer detail and to elucidate how NO targets
      biological systems, especially in relation to its pathophysiological role.

PMID- 8533008
TI  - Cytochrome P450: structure, function, and generation of reactive oxygen species.

PMID- 8533009
TI  - DNA damage profiles induced by oxidizing agents.

PMID- 8533010
TI  - Depolarization-transcription coupling in excitable cells.

PMID- 8533011
TI  - Chemistry and pathophysiology of oxidation of LDL.

PMID- 8533012
TI  - p53: DNA damage, DNA repair, and apoptosis.

PMID- 8533013
TI  - Biosynthesis of nitric oxide: dependence on pteridine metabolism.

PMID- 8533014
TI  - Prevalence and risk factors of HIV-1 infection in three parishes in western
      Uganda.
AB  - A population-based serosurvey was conducted to determine the HIV-1 prevalence and
      to evaluate various risk factors in three parishes in western Uganda. Adults over
      14 years were examined in all 13 villages of Kigoyera parish far from Fort
      Portal, in two villages of Kyamukoka parish closer to Fort Portal and in the four
      fishing villages of Ntoroko parish at Lake Albert with a high population
      mobility. Personal interviews and HIV serology using ELISA and Western blot were
      performed. Sera showing at least two envelope bands in the Western blot were
      considered as positive. The coverage of the registered eligible population was
      74% in Kigoyera, 67% in Kyamukoka and 25% in Ntoroko. The prevalence of HIV was
      4% (97 of 2267 persons examined, 95% CI 3.4-5.1%) in Kigoyera, a typical rural
      area. Whereas it was 13% (53 of 393 persons examined, 95% CI 10.1-16.9%) in
      Kyamukoka near to the district capital and exceptionally high with 24% (96 of 399
      persons examined, 95% CI 19.9-28.3%) in the comparatively isolated fishing
      villages of Ntoroko. In a multivariate model the infection risk for HIV was in
      Kyamukoka two and in Ntoroko five times higher than in Kigoyera. Among the two
      main ethnic groups one had a significantly lower risk to acquire HIV infection
      than the other group. CONCLUSIONS: Because of their large proportion of migrating
      persons the fishing villages presented populations with high risks for HIV
      infection. The ethnic composition of the village population, representing group
      specific sexual behaviour, was a risk factor for HIV infection.

PMID- 8533015
TI  - Changes in malaria associated morbidity in children using insecticide treated
      mosquito nets in the Bagamoyo district of coastal Tanzania.
AB  - A community based malaria control intervention using insecticide treated mosquito
      nets (IMN) has been implemented and tested in 13 villages of the Yombo Division,
      Bagamoyo District in the Coastal Region, Tanzania, an area holoendemic for P.
      falciparum malaria. Following extensive sociological research into local
      perceptions of malaria, the programme was implemented. It wa decided by consensus
      that village mosquito net committees would be the appropriate local level
      implementors. These were formed and provided with IMN's which were sold to
      villagers at subsidised cost. The income was invested for use by the committees
      for sustaining the activity. Use patterns were determined and high coverages were
      obtained among the community, particularly after promotions e.g. plays, school
      meetings etc. Malaria morbidity was measured among children 6-40 months of age in
      7 index villages prior to the intervention in 1992 and in a comparison study
      between 3 villages using nets and 4 villages not using nets in 1993. Examination
      of the 7 cohorts of children was done from June to October each year covering the
      period of most severe transmission. The children using nets showed marked
      improvement in several malariometric indices. Following an initial clearance of
      parasitaemia with sulphadoxine/pyrimethamine, when compared with unprotected
      children, those with nets were slower to become re-infected (Relative Risk 0.45),
      had lower parasitaemias and showed marked improvement in anaemia (RR 0.47). Use
      of IMN's produced a 54% reduction in the prevalence of anaemia among young
      children. Attempts are being made to ensure that the programme is locally
      sustained.

PMID- 8533016
TI  - Evaluation of circumsporozoite antibody testing as a sero-epidemiological tool
      for the detection of Plasmodium falciparum infection in non-immune travelers.
AB  - The objective of this investigation was to collect data concerning CS-antibody
      levels and duration of the immunological response to exposure of non-immune
      persons to a single malaria infection. For this purpose 156 specimens from 98
      patients with confirmed falciparum malaria, 76 specimen derived from 64 patients
      with vivax malaria and sera from 32 patients who had not been previously to
      malarious areas were investigated by use of a commercially available ELISA
      testkit. All specimens from patients with falciparum malaria were also tested for
      merozoite-antibodies by an indirect fluorescence antibody test (IFAT). Positive
      levels of merozoite-antibodies were detectable in 89.1% of the specimen in this
      panel during the period between days 8 and 90 after onset of symptoms and
      decreased steadily thereafter. The test results were positive for CS-antibodies
      in 36.4% of the specimens from patients with falciparum malaria during the first
      7 days after onset of symptoms. This figure increased to 55.8% during days 8-90
      after onset and decreased to 38.9% in specimens which were tested later (91-1898
      days). 11 specimens reacted positively to CS-antibody testing but negative in the
      IFAT. Therefore, the percentage of specimen detected by either IFAT or CS-ELISA
      was at 51.9% during days 0 and 7 (p < 0.001), 95.3% during days 8 and 90 (p =
      0.039) and 44.4% for testing performed later (p < 0.001). CS-antibodies could
      also be detected in 5.3% of specimen from patients with vivax malaria while none
      of the sera from the malaria-negative control-group tested positive for CS
      antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533017
TI  - Human pharmacokinetics of chloroquine and proguanil delivered in a single capsule
      for malaria chemoprophylaxis.
AB  - Two antimalarial prophylactic regimens were compared in 17 healthy volunteers.
      Regimen A consisted of daily ingestion of a single capsule containing 100 mg base
      chloroquine (CQ) and 200 mg proguanil (PG). Regimen B consisted of daily
      ingestion of separate tablets of CQ (100 mg base) and PG (two 100 mg tablets).
      Both treatments lasted for 12 days. Effective chloroquine levels were reached
      after 72 hours with both regimens (49.9 ng/ml for treatment A and 36.7 ng/ml for
      treatment B). Proguanil and cycloguanil plasma levels were significantly lower on
      sampling obtained at H3 (three hours later) and H6 (six hours later) on day 1 in
      the regimen A (p < 0.002). Thereafter there were no significant difference
      between the two regimens. Both regimens were well tolerated, but regimen A using
      the capsule appeared better accepted and facilitates compliance.

PMID- 8533018
TI  - Stand-by treatment of suspected malaria in travellers.
AB  - Travellers to malarious areas are increasingly advised to carry an emergency
      medication for self-treatment of suspected malaria in absence of medical
      attention. However, no data are available so far how travellers cope with self
      diagnosis and stand by treatment (SBT). We therefore investigated the frequency,
      circumstances and outcome of emergency self-treatment for suspected malaria in
      German travellers. 3434 travellers were recruited for an open prospective study
      by 28 different travel clinics in Germany. 2867 travellers (90.1%) who returned
      questionnaires after their journey were analyzed. 40 travellers (1.4%) reported
      about SBT during their journey. Significant Plasmodium falciparum antibody levels
      could be demonstrated in only 4 of 37 SBT users (10.4%). In another 127
      travellers with febrile episodes but without SBT use, no malaria was indicated by
      follow-up and/or serology.

PMID- 8533019
TI  - Vectorial capacity and entomological inoculation rates of Anopheles gambiae in a
      high rainfall forested area of southern Sierra Leone.
AB  - We report the first study of gonotrophic cycle duration, survival rates, pre
      gravid rates, vectorial capacity and chromosomal polymorphism of Anopheles
      gambiae s.s. in Sierra Leone. In the village of Bayama in the Southern Province,
      An. gambiae was the only species found to be naturally infected with Plasmodium
      falciparum and it constituted 99.7% of 22,541 anopheline mosquitoes caught.
      Chromosomal studies revealed only An. gambiae s.s. out of 66 females examined for
      chromosomal polymorphism, 61 (92.4%) had the 2LA inversion in the standard
      arrangement. Other inversions observed in low frequencies included 2Rcu and 2Ru.
      We estimated a gonotrophic cycle length of three days and survival rate per
      gonotrophic cycle of 0.59 for this species. The mean daily survival rate of An.
      gambiae was 0.85 and the entomological inoculation rate was 1,235 infective
      bites/person/year. Blood-meal ELISA tests showed that the species was very
      anthropophagic and that there were an estimated 35.4 daily inoculations per
      infective case. The epidemiological significance of these entomological
      parameters is discussed in the light of parasitological results for nearby
      villages.

PMID- 8533020
TI  - Babesia canis: evidence for genetic diversity among isolates revealed by
      restriction fragment length polymorphism analysis.
AB  - The genetic diversity of B. canis was investigated by restriction fragment length
      polymorphism analysis. For this purpose, we identified a Babesia canis specific
      DNA probe named pS8. This 1.2 kbp probe can detect as low as 20 pg of B. canis
      DNA. Results suggest that the pS8 probe is distributed in multiple copies
      throughout the genome though is probably not itself internally repetitious, i.e.
      not structured into blocks of tandem units. This probe reveals discrete
      hybridizing fragments in B. canis enzyme-digested genomic DNA. RFLP patterns
      obtained with the pS8 probe revealed a large genetic diversity between various
      isolates and led us to distinguish several clones derived from a single isolate.
      Results suggest that for a single isolate, the fingerprints obtained reflect
      those of a few quantitatively dominant clones. This technique can now be
      routinely applied and provides a convenient tool for the characterization and the
      identification of B. canis isolates, strains and clones.

PMID- 8533021
TI  - Evaluation of three serological tests for the detection of antiamebic antibodies
      applied to sera of patients from an area endemic for amebiasis.
AB  - Two enzyme immuno assays based on a single recombinant Entamoeba histolytica
      antigen (P1-EIA) or soluble E. histolytica extract (SA-EIA) as well as a latex
      agglutination test using an E. histolytica membrane fraction (M-LA) were
      evaluated for its use to detect anti-amebic serum antibodies in patients from
      Durban, South Africa, an area endemic for amebiasis. In a previous study, all
      three test systems were found to be reliable in terms of sensitivity and
      specificity when applied to sera of European individuals. By analysing a total of
      167 serum samples of patients from the Durban area, suffering from invasive
      amebiasis (n = 76) or miscellaneous diseases unrelated to E. histolytica
      infection (n = 91), the present study revealed sensitivity for the detection of
      anti-amebic antibodies of 97.4% for SA-EIA, 86.8% for P1-EIA and 96.1% for M-LA,
      respectively. Specificity was high for P1-EIA (96.7%) and M-LA (92.3%) but
      substantially lower for SA-EIA (62.6%). In addition, antibody responses to the
      recombinant P1 antigen were analysed in 16 patients with amebic liver abscess
      before and after anti-amebic treatment. The results indicated that most of the
      patients lost their specific antibody response within 7 month of follow up.
      Therefore, P1-EIA seems to be a valuable test for distinguishing between present
      and past E. histolytica infections.

PMID- 8533022
TI  - Successful application of deltamethrin pour on to cattle in a campaign against
      tsetse flies (Glossina spp.) in the pastoral zone of Samorogouan, Burkina Faso.
AB  - 1,500-2,000 head of cattle were treated with deltamethrin 1% Spot On in an area
      of high tsetse densities, notably of Glossina morsitans submorsitans. After four
      treatments at monthly intervals, the time between two treatments was increased to
      two months. 11 months after the commencement of the campaign the fly population
      had decreased from initially 54.2 flies/trap/day to densities varying between
      0.06-2.0 flies/trap/day, mostly G. palpalis gambiensis. Blood-meal analysis
      showed that this species was surviving in limited areas, mainly feeding on
      monitor lizards; consequently it is unlikely that this species can be eradicated
      solely by the use of cattle treated with a pyrethroid. The resistance of
      Trypanosoma congolense to all commercially available trypanocides necessitated
      the epidemiological monitoring of calves which were born after the start of the
      campaign in order to reasses the real challenge. The risk of new infections was
      low, basically due to contracts between the cattle and tsetse outside the
      ranching area. A weight increase from 122.3 kg to 213.6 kg of calves aged 6-12
      months was recorded from October 1993 to October 1994. An average daily weight
      gain of more than 400 g was observed from the end of April 1994 to the beginning
      of August 1994.

PMID- 8533023
TI  - Innate lack of susceptibility of Ugandan Trypanosoma brucei rhodesiense to DL
      alpha-difluoromethylornithine (DFMO).
AB  - Trypanosoma brucei rhodesiense isolates from South East Uganda were characterized
      for susceptibility to the drugs suramin, nifurtimox, melarsoprol and DL-alpha
      difluoromethylornithine (DFMO). Two different assays were used to determine the
      drug susceptibility of the field isolates: the [3H]hypoxanthine incorporation
      assay (24 hours) and the long term viability assay (10 days). All trypanosome
      stocks were susceptible to suramin and nifurtimox. Differences in the
      susceptibility to melarsoprol were observed in the [3H]hypoxanthine incorporation
      assay, but could not be confirmed in the long term viability assay. All T. b.
      rhodesiense stocks were found in vitro to have innate tolerance to DFMO, under
      conditions where T. b. gambiense stocks from West Africa were susceptible to the
      drug. Ugandan T. b. rhodesiense stocks did respond to 25-100 micrograms/ml after
      10 days of drug exposure, but the DFMO level reached in cerebrospinal fluid
      during treatment is only 16.3 +/- 7.8 micrograms/ml. Therefore, DFMO is not an
      appropriate alternative or backup drug for treatment of Rhodesian sleeping
      sickness in Uganda.

PMID- 8533024
TI  - Characterization of Paraguayan Trypanosoma cruzi strains isolated from acute
      patients of Chagas disease.
AB  - Five Paraguayan Trypanosoma cruzi strains, isolated from acute chagasic patients,
      were studied by their behavior in BALB/c mice, metacyelogenesis, bio-metry of
      metacyclic forms and lectin agglutination. Early and intermediate parasitemic
      peaks were observed and the strains did not show high virulence. Metacyclogenesis
      capacity was not higher than 50% in all cases and there were no considerable
      differences in the biometry. They all belong to WGA-type strains according to the
      lectin agglutination assays except for one strain that agglutinated with WGA and
      PNA lectins. Although previous schizodeme analysis of these strains showed rather
      homogeneous profiles, biological features were quite heterogeneous.

PMID- 8533025
TI  - A simple field method for the purification of Onchocerca ochengi microfilariae
      from a mixed Onchocerca infection in cattle.
AB  - Onchocerca ochengi, a bovine parasite, is a suitable model for research on human
      River Blindness. However, the microfilariae are normally found concomitantly with
      at least one of the other three bovine Onchocerca species O. dukei, O. gutturosa
      and O. armillata causing difficulties for the work on the microfilariae. We
      describe a simple and field applicable method for the separation of living O.
      ochengi microfilariae from the other Onchocerca species using Sephadex G-25
      columns. Elution of mixed populations resulted in the passage of O. gutturosa
      and/or O. dukei in the initial 1 ml fraction with O. ochengi eluting as an almost
      100% pure species in the 4th and 5th fractions.

PMID- 8533026
TI  - Large scale collection of viable infective larvae of Loa loa.
AB  - A simple method to obtain large numbers of viable infective larvae (L3) of the
      human filarial parasite Loa loa in an endemic country is described: wild vector
      flies (Chrysops silacea and C. dimidiata) were caught in large numbers, sealed
      into pockets of mosquito netting, gently crushed on a glass plate and incubated
      in a funnel with medium ("Baermann technique"). 91-94% of the L3 actively left
      the crushed flies and accumulated in the funnel tip after 15 (80%) to 45 minutes
      (95%). During 111 catching days over a 12 month period, a single fly collector
      provided approximately 13,000 flies and 23,500 L3. The method is also considered
      useful for assessing loiasis-transmission, for example before and after mass
      treatment campaigns.

PMID- 8533027
TI  - [Proficiency testing for chemical analytical laboratories--general principles
      concerning organization and assessment of results].
AB  - In order to promote in Poland the effective response to the international food
      regulations and to enhance the ability of laboratories in proving their
      analytical quality assurance, some general guidelines for proficiency testing
      have been presented according to the internationally recognised protocol
      (IUPAC/ISO/AOAC The International Harmonized Protocol for Proficiency Testing).
      The objectives of proficiency testing and its importance for accreditation for
      analytical laboratories were also reviewed with the special emphasis given to
      those dealing with food analysis. The organization of interlaboratory trials and
      methods for statistical treatment of results were also described, as well as
      reporting of results and their statistical evaluation. The proficiency testing
      according to the above described rules are routinely performed by the Department
      of Environmental Toxicology of the National Institute of Hygiene for
      organochlorine pesticides and PCBs in food.

PMID- 8533028
TI  - [Residues of chlorinated hydrocarbons in milk].
AB  - In 1994 samples of bovine milk were taken in 98 sampling points (2 in each of 49
      districts of Poland). Levels of organochlorine pesticides and polychlorinated
      biphenyls (PCB) were determined by capillary gas chromatography. In almost all
      milk samples DDT and PCB residues were found. Mean concentration of sigma DDT in
      milk fat was 0.065 mg/kg (from 0.011 mg/kg to 0.382 mg/kg) and PCB 0.017 mg/kg
      (from 0.007 mg/kg). Other organochlorine pesticides (mainly HCH isomers and HCB)
      were found in low levels and only in some samples--HCB and gamma-HCB in about
      60%, alpha-HCH in 30% of all tested samples. Results of our 20-year study
      indicate that organochlorine pesticide levels in milk has decreased ten fold
      during that time.

PMID- 8533029
TI  - [Mercury in muscle tissue of flounder Platychthis flesus from two sites in the
      Gulf of Gdansk].
AB  - Total mercury concentration was determined in the muscle tissue of flounder
      collected under Stegna (ca. 1 mile east of the Vistula River outlet) and under
      Gdynia (ca. 12 miles northwest of the Vistula River Outlet) sampling sites in the
      Gulf of Gdansk in 1992 and 1993. The method of measurement was cold-vapour atomic
      absorption spectrometry (CV-AAS) after wet digestion of the samples with
      concentrated nitric acid. The arithmetic means of mercury concentration in muscle
      tissue of flounder collected under Stegna were 46 +/- 24 in 1992 and 57 +/- 47 in
      1993, while for those under Gdynia 20 +/- 19 and 26 +/- 18, micrograms/kg on a
      wet weight basis, respectively. Mercury concentrations in muscle tissue of
      flounder collected under Stegna were positively correlated with the body length
      and body weight of fish (0.05 < p < 0.001), while in the case of specimens
      collected under Gdynia no such relationships were found. These observations seem
      to imply that Vistula River is an important source and pathway of mercury
      entrance into the Gulf of Gdansk.

PMID- 8533030
TI  - [Determination of Alternaria mycotoxins in selected raw and processed fruit and
      vegetable products].
AB  - The purpose of the study was the assessment of Alternaria-mycotoxins
      contamination in some raw and processed plant products. The analytical method for
      detection of alternariol (AOH) and alternariol methyl ether (AME) is described.
      After extraction and purification of sample crude extracts by column
      chromatography on silica gel, the qualitative and quantitative analyses were
      carried out by two-dimensional TLC. There were 110 samples analyzed -44 (included
      32 moulded) raw plant samples and 56 processed plant products. Levels of
      alternaria-mycotoxins found in fruits and tomatoes visibly decayed ranged between
      3 to 420 micrograms/kg for AOH and 10 to 100 micrograms/kg for AME. Trace amounts
      of AOH were detected in 3 samples of processed products.

PMID- 8533031
TI  - [Effect of various thawing techniques on the quality of small fruit frozen
      products].
AB  - The investigation concerned the effect of three methods of thawing frozen
      products at 18-20 degrees C (room temperature), 2-4 degrees C (conditions of a
      domestic refrigerator), and in a microwave oven, on the quality of fruit of blue
      berry, raspberry, black- and red currant, and strawberry. Physico-chemical
      indices applied as the criteria of the estimate were the content of dry matter,
      volatile acids, vitamin C, and anthocyanins, the amount of cell sap exuded after
      thawing, and the results of organoleptic evaluation. After harvest fruits were
      kept in a cold store and processed within 24 h. Frozen products were stored at
      about -30 degrees C up to the time of degustation. From the practical point of
      view the applied techniques of thawing insignificantly affected the level of the
      physico-chemical indices. Only in the case of fruit affected by microwaves the
      content of vitamin C (black currant) and anthocyanins (blue berry, raspberry, and
      black currant) was smaller, though maximum differences did not exceed 10%. The
      amount of cell sap exuded in the course of thawing depended on the fruit species
      and method of thawing. Blackcurrant exuded trace amount of sap, greater ones were
      noted, in the increasing order, with bilberry, raspberry, and strawberry, and the
      greatest with redcurrant. Of the thawing techniques tested the smallest amount of
      sap exuded at 2-4 degrees C, at 18-20 degrees it was by 30% and in the microwave
      oven by 63% greater.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533032
TI  - [Determination of total amounts of mercury in unfrothing preparations].
AB  - Mercury and its organic (CH3 HgCl) and inorganic (HgCl2) compounds are very
      poisonous. The analytical control of trace amounts of metals in products that are
      used in the food industry is of great importance. In this work, the determination
      of mercury, present at trace levels in industrial unfrothing preparations.
      Mercury was determined by the cold-vapour atomic absorption spectrometry. The
      method allows for accurate determination of mercury and as little as 0.01 mg ph
      Hg per kilogram of product can be determined.

PMID- 8533033
TI  - [Dust particles and metals in outdoor and indoor air of Upper Silesia].
AB  - This work contains the results of the aerosol mass size distribution and
      preliminary studies on concentrations and size distribution of heavy metals (Pb,
      Zn, Cu, Mn, Fe and Cd) in indoor and outdoor environment in Upper Silesia (the
      highly industrialized region in the southern part of Poland). In studies, the
      measurements of aerosol concentration, mass size distribution, and evaluation of
      heavy metals concentration were made from December 1992 to April 1994 in some
      apartments in five towns in Upper Silesia and in one village in the Beskidy
      Mountains in both indoor and outdoor environments. The particles were
      fractionated in Andersen cascade impactor. The sampling time was 6-7 days and 4-5
      days for indoor and outdoor respectively. Aerosol particulates were collected on
      A-type glass fiber collection substrate used later for determination of heavy
      concentrations by atomic absorption spectrophotometry (AAS 3, Carl Zeiss Jena).
      The dust was mineralized by the means of the mixture of hydrofluoric and nitric
      acids. The results of mass size distribution as well as the measurements of TSP
      for indoor and outdoor aerosol show that the main source of particulate matter
      indoors, in this region, are heavy polluted outdoor air and cigarette smoking. It
      can be said that, except homes in Knurow and Sosnowiec with hard smokers, the
      indoor levels of particulate pollution were significant lower than the outdoors
      levels. Whenever in the indoor environment appear additional source of
      particulate emission situation can changed. When we compare mass size
      distribution for outdoor aerosol and indoor aerosol contaminated by tobacco
      smoke, we can observed considerable increase of indoor aerosol level in the 0.33
      0.54 microns size range. Besides, indoor aerosol status may be changed by coal
      stove emission (displacement of maximum peak to direction of coarse particles).
      The observed differences in concentration of particulate matter may also indicate
      the important differences in chemical and physical nature of particles caused by
      the air filtration and absorption during migration of ambient air into the indoor
      environment. On the base of comparison of the heavy metals concentrations of fine
      and coarse fraction and their indoor/outdoor ratio in five selected towns in
      Upper Silesia it can be said that the level of heavy metals in indoor aerosol is
      lower than in outdoor (except Pb and Cd) what suggest that migration of ambient
      air into the homes is a major process which give indoor air contamination of
      heavy metals.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8533034
TI  - [Draize test and alternative methods for evaluating irritation from chemical
      substances].
AB  - The eye irritancy test in rabbits (Draize test) is currently the method used to
      evaluate the hazard or safety of chemical substances. To reduce the need for
      animal testing some new procedures as alternative were elaborated. We present a
      review of method used as well as evaluation of sensitivity and repeatability of
      alternative tests applied in laboratories of European Economic Communities.

PMID- 8533035
TI  - [Evaluation of the combined effect of copper chloride and sodium nitrate on blood
      methemoglobin and tryptophan level in rats (subchronic exposure)].
AB  - The study was performed on 4 groups of male Wistar rats, receiving p.o. through 3
      months every day: 1) sodium nitrite in dose 30 mg/kg b.w. x day (0.2 LD50); 2)
      copper chloride in dose 4.67 mg/kg b.w. x day (0.03 LD50); 3) copper chloride and
      sodium nitrite in amounts as above, and 4 - control group - received distilled
      water. The methemoglobin and hemoglobin were determined in whole blood and
      tryptophan in plasma 24 hours after the last intoxication. There was showed, that
      every day intoxication of rats with sodium nitrite cause the increase of
      methemoglobin concentration and decrease the free tryptophan level in the blood.
      There was also observed, that copper chloride, administrated together with sodium
      nitrite, decreases significantly his methemoglobin creating action.

PMID- 8533036
TI  - [Effect of water contamination with surface active substances and plant
      protecting agents on aquatic organisms].
AB  - The purpose of the study was establishing in what degree the presence of surface
      active substances affects the influence of herbicides present in surface waters
      on aquatic organisms. The study was carried out under laboratory conditions using
      as herbicides promethrin (triazine group) and dichlorophenoxy-acetate sodium (2,4
      D), and detergents - sodium alkylsuphonate ABS and non-ionic detergent Rokafenol
      N8P7. The effect of these substances was studied on the test organisms from own
      cultures - Daphnia magna Straus, larvae of insects Chironomus plumosus L, and
      young fish Lebistes reticulatus. The study showed that promethrin was the
      herbicide with stronger action on the studied organisms than 2,4 D. The presence
      of single detergents and their mixtures increased promethrin effects by 10-13% on
      the testes invertebrates even in concentrations permitted in surface waters. The
      toxic effect of the herbicide 2,4 D was potentiated by detergents in much higher
      concentrations, exceeding the permitted values. Contamination of surface waters
      with detergents may endanger the trophic chain of aquatic biocenoses.

PMID- 8533037
TI  - [The breakdown of the fungicide carbendazim in an aqueous environment].
AB  - The study of the breakdown of the fungicide carbendazim widely used in Poland was
      carried out under model conditions simulating the environment of river water
      moderately polluted, distilled water, and dynamic aqueous ecosystem. The
      experiments were conducted using the fungicide in concentrations about 1 and 5
      mcg/l at two temperatures-about 20 degrees C and 5 degrees C, and after
      adaptation of microorganisms to the presence of the fungicide. Taking the results
      of the experiment with river water the rate of the breakdown was studied,
      determining also the kinetic parameters of the breakdown process: rate constants
      and half-times of breakdown. This process agreed, as a rule, with the kinetic
      equation of first order and depended on the type of water, initial concentration,
      temperature and microflora adaptation to the environment of the tested substance.
      The process of carbendazime breakdown after adaptation of the microorganisms of
      river water to the fungicide was occurring at a much higher rate at both test
      temperature and depended on the initial concentration. Temperature decrease to
      about 5 degrees C inhibited the process of carbendazime degradation, but only if
      the initial concentration was higher. The concentrations of carbendazime in
      aqueous environment under dynamic conditions during 14-day exposure decreased by
      14-19% and had no negative influence on the biocenosis of the experimental
      ecosystem Carbendazime was not taken up by water-thyme and Lebistes reticulata in
      the experimental ecosystem, was poorly concentrated by snails and accumulated
      slightly in the sediments of the ecosystem.

PMID- 8533038
TI  - [Disinfection of wood in mushroom growing cellars with Mycetox].
AB  - Since the use od phenolic disinfectants for impregnating and disinfecting of wood
      in mushroom--growing cellars was banned in Poland for ecologic and hygienic
      reasons, the new product, namely Mycetox, containing quaternary ammonium compound
      and boric acid has been registered for this purpose. Mycetox belongs to new
      generation products and is non toxic for man and the environment. It is first
      Polish product developed for the general disinfection as well as for impregnating
      purposes in mushroom farms. The efficacy of Mycetox in mushroom-growing cellars
      has been evaluated basing on its fungicidal properties in the different
      substrates used for the cultivation of mushrooms. Also its influence on mushroom
      spawn growth, crop yield, and the penetration of spawn into wooden cages
      impregnated with Mycetox as well as its influence on blanching of mushrooms has
      been investigated.

PMID- 8533039
TI  - Nervous system lupus: pathogenesis and rationale for therapy.
AB  - Several different pathogenic mechanisms appear to be involved in CNS lupus. These
      include: B-cell/autoantibody-mediated nervous system compromise; immune complex
      deposition and vasculitis; microthrombosis and vasculopathy; aberrant MHC Class
      II antigen expression with T-cell mediated disease (multiple-sclerosis model);
      and, cytokine-induced brain inflammation. These processes are not mutually
      exclusive: there exist in vitro and in vivo models for each of these. A number of
      autoantibodies, especially those with specificities for shared
      neuronal/lymphocyte antigens, are associated with certain forms of cognitive
      dysfunction or overt nervous system manifestations. In MRL/lpr mice, lymphoid
      infiltrates in the brain parenchyma are related to a neurobehavioural dysfunction
      which develops very early in the course of autoimmune disease. Recent results,
      both in animal models and in human studies on the therapeutic effects of
      corticosteroids, immunosuppressive drugs or anticoagulants on clinical and
      subclinical manifestations of CNS lupus are highlighted in an attempt to develop
      a rationale for intervention based upon presumed pathogenesis.

PMID- 8533040
TI  - William Musgrave's (1655-1721) system of arthritides. Did it include rheumatoid
      arthritis?
AB  - Three dissertations on arthritis in Latin by the Englishman William Musgrave have
      been reviewed to find possible descriptions of rheumatoid arthritis.
      Polyarticular long-lasting joint pain in women are the cases most probable to be
      rheumatoid arthritis. This was found in 18 of 150 case stories. In the general
      sections the description of an arthritis after rheumatism has many traits
      compatible with rheumatoid arthritis. This sort of arthritis is reported to be
      frequent. It seems reasonable to conclude that rheumatoid arthritis was not
      uncommon at the turn of the seventeenth and eighteenth centuries. The
      difficulties in diagnostic interpretation of old medical texts are demonstrated.

PMID- 8533041
TI  - The value of the ACR 1987 criteria in very early rheumatoid arthritis.
AB  - We assessed the sensitivity and specificity of the ACR 1987 revised criteria for
      rheumatoid arthritis (RA) in 121 patients with recent-onset (< or = 6 months) RA,
      68 with reactive arthritis (ReA), 19 with ankylosing spondylitis (AS), and 13
      with psoriatic arthritis (PsA). The sensitivity of each single criterion ranged
      8.3-90.9% and specificity 52.0-100%. The sensitivity of four fulfilled criteria
      was 83.5% and specificity 86.0%. In ReA 11.8%, AS 5.3%, and PsA 38.5% of patients
      fulfilled four criteria respectively. Thus at the beginning of RA, 83% of
      patients could be diagnosed correctly by using the ACR 1987 criteria, and the
      remaining 17% had seropositive and/or erosive arthritis at the onset. The
      suitability of the radiographic ACR criteria is discussed.

PMID- 8533042
TI  - Evaluation of a Swedish version of the arthritis self-efficacy scale in people
      with fibromyalgia.
AB  - The major purpose of this study was to determine the utility and construct
      validity of the Swedish version of the Arthritis Self-Efficacy Scale (ASES-S).
      Ninetynine women with fibromyalgia (FS) were included in a randomized, controlled
      trial of fibromyalgia efficacy-based self-management education and physical
      training. Several self-report instruments were used to evaluate the outcome of
      the intervention. Evidence of construct validity of the ASES-S was revealed in
      the factor analysis which produced a three factor solution similar to previous
      results. Significant correlations between ASES-S and pre and post health status
      measures were consistent with theoretically derived hypotheses, further
      testifying to construct validity. Multiple regression analyses confirmed that
      pretest ASES-S was the strongest predictor of posttest ASES-S. The results
      indicated that the intervention had produced a significant change in ASES-S and
      that this positive change in self-efficacy was associated with changes in health
      status. In conclusion, this study has shown the ASES-S to be a valid measure of
      treatment effects also for patients with FS.

PMID- 8533043
TI  - Detection of antibodies to HIV-1 gp41- and HLA class II antigen-derived peptides
      in SLE patients.
AB  - A role for viruses in the pathogenesis of human autoimmune diseases has long been
      suspected but has not yet been proven. Highly conserved homologous regions has
      been reported in the carboxy terminus of human immunodeficiency virus (HIV)-1
      gp41 (amino acids 838-844) and the amino-terminal of the beta chain of all human
      HLA class II antigens (amino acids 19-25). This molecular mimicry between HIV-1
      and HLA class II antigens may lead to the generation of autoantibodies and may
      contribute to the development of autoimmune phenomena in HIV infected patients.
      We detected antibodies for these homologous peptides from HLA class II and HIV-1
      gp41 in systemic lupus erythematosus (SLE) patients without HIV-1 infection.
      Thirty-seven percent of the SLE patients had IgM antibodies reacting with both
      HLA class II- and HIV-1 gp41-derived peptides. These results suggest the
      possibility that a retrovirus may be one of the causative agents of SLE.

PMID- 8533044
TI  - Phosphorylation profiles of 60 kD Ro antigen in synchronized HEp-2 cells.
AB  - The purpose of this study was to determine whether phosphorylation has an effect
      on the characteristics of the 60 kD Ro antigen throughout the cell cycle. Cell
      extracts of synchronized HEp-2 cells were phosphorylated in vitro with exogenous
      ATP, examined by SDS-PAGE and Western blot, and probed with specific anti-Ro
      sera. In addition, cellular ATP pools were radiolabelled in vivo with 32P. The
      presence of the Ro protein was detected with a molecular weight of 60 kD during
      all phases of the cell cycle, except at the M phase, where it was increased to 65
      kD. Phosphorylation of the in vitro and in vivo cell extracts increased the
      molecular mass to 65 kD. Moreover immunoprecipitation assays demonstrated that Ro
      is hyperphosphorylated in the M phase. Phosphorylation did not change the
      recognition pattern of the anti-Ro sera.

PMID- 8533045
TI  - Tracheo-bronchial mucociliary clearance in patients with primary and secondary
      Sjogren's syndrome.
AB  - We determined the tracheo-bronchial mucociliary clearance (MCC) in order to
      evaluate a possible impairment of this function in patients affected by Sjogren's
      syndrome (SS) with or without overt clinical symptoms of xerotrachea. The MCC was
      expressed as flow rate (mm/min) and studied in 22 non-smoking SS patients (10 pSS
      and 12 sSS) and in 8 control subjects by specifically adapted ventilation lung
      scintigraphy (VLS). The MCC in the control group was 5.9 +/- 1.1 mm/min. No
      values were produced for MCC in 16 SS patients (8 pSS and 8 sSS) in the time
      interval considered and were reduced in the remaining 6 SS patients (3.3 +/- 1.2
      mm/min). In all nine cases with clinical evidence of xerotrachea no values for
      MCC were obtained. A significant correlation was found between the MCC values and
      the rate of stimulated salivary excretion determined by dynamic
      scialoscintigraphy in the same patients (p < 0.001). These preliminary data show
      that the majority of SS patients studied presented with MCC impairment, always
      found when clinical symptoms of xerotrachea were present.

PMID- 8533046
TI  - The accuracy of MRI-determined synovial membrane and joint effusion volumes in
      arthritis. A comparison of pre- and post-aspiration volumes.
AB  - Magnetic resonance imaging (MRI) of 18 knees of patients with arthritis was
      performed before and immediately after arthrocentesis. Pre- and post-aspiration
      volumes were calculated by adding the outlined areas of synovium/effusion from a
      continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted MR
      images. The difference between MRI-determined and syringe-determined volumes of
      aspirated joint fluid was 0-7 ml, median 2 ml, corresponding to 0-18%, median 7%,
      of the pre-aspiration effusion volume. Synovial membrane volumes, determined
      before and after arthrocentesis varied 0-10 ml, median 3 ml (0-17%, median 7%).
      No significant systematic misinterpretation of the borderline between joint fluid
      and synovium was found. We conclude that effusion volumes and in all probability
      also synovial membrane volumes, can be determined by MRI with a maximal
      analytical error of approximately 20%. The acceptable accuracy of the method
      encourages further studies of the value of effusion and synovial membrane volumes
      as markers of the activity and/or severity of joint inflammation.

PMID- 8533047
TI  - Detection of plantar tenosynovitis of the forefoot by ultrasound in patients with
      early arthritis.
AB  - Clinical examination, dorsoplantar radiographs and transverse sonographic scans
      of the plantar region of the forefoot were performed on 35 healthy individuals as
      well as 25 patients with inflammatory joint disease and forefoot symptoms. The
      ultrasound revealed twenty plantar flexor tenosynovitides in 12 of the 25
      patients. In 14 out of the 20 tenosynovitides there was no metatarsophalangeal
      effusion in the same digit. Thus, also plantar tenosynovitis and not only
      metatarsophalangeal arthritis can promote symptoms of the forefoot. Only in eight
      of the 20 tenosynovitides the clinical examination was positive. Ultrasound is a
      more objective procedure than clinical examination in diagnosing plantar
      tenosynovitis. This finding has not only a diagnostic but also a therapeutic
      implication.

PMID- 8533048
TI  - Age and spinal mobility in ankylosing spondylitis.
AB  - Mobility measurements of spine, chest, hips, and shoulder in 73 adult males with
      ankylosing spondylitis (AS) were correlated with the duration of disease. Several
      mobility tests showed a significant correlation with the duration of AS, but
      after adjustment for age, only rotation of the thoracolumbar spine maintained a
      highly significant correlation. It is concluded that age has a strong effect on
      the mobility tests. Rotation of the thoracolumbar spine seems to be a valid
      measure for AS-specific changes.

PMID- 8533049
TI  - Sjogren's syndrome terminating with multiple myeloma.
AB  - We describe a patient (49 years old, female) with a more than 7-year history of
      both Sjogren's syndrome (SjS) and benign monoclonal gammopathy (BMG) of IgG
      lambda who later developed multiple myeloma (MM). SjS is frequently complicated
      with malignant lymphoproliferative disorders, especially malignant lymphoma or
      Waldenstrom's macroglobulinemia. Association of SjS with MM seems to be extremely
      rare, although BMG has been observed frequently in SjS, and there are many
      reports concerning the association between rheumatoid arthritis and MM.

PMID- 8533050
TI  - Familial Pelger-Huet anomaly accompanied by tuberculosis and complicated by acute
      polyarthritis.
AB  - A patient with familial Pelger-Huet (PH) anomaly, which accompanied tuberculosis,
      and acute polyarthritis is described. Investigations surrounding this case
      suggests that the immunological abnormalities may be associated with the PH
      anomaly and the tuberculosis, and that the complications may be related to the
      development of the acute polyarthritis.

PMID- 8533051
TI  - HLA-B27 negative ankylosing spondylitis in a father and a son.
AB  - Only 5% of AS patients are B27 negative. We describe two cases of HLA-B27
      negative AS in a father and a son who both developed clinical and radiological
      features characteristic of AS. Tissue typing for HLA-A,-B,-C was performed in all
      1.degree family members except for the father who died in 1990. All family
      members possessed B40. HLA-B40 may contribute to an increased susceptibility for
      AS not only in B27 positive individuals but also in B27 negative cases.

PMID- 8533052
TI  - Migratory polyarthritis associated with Plesiomonas shigelloides infection.
AB  - Migratory polyarthritis was observed in a child with Plesiomonas shigelloides
      infection of the gastrointestinal tract. All symptoms and signs of arthritis
      resolved following successful treatment of infection with the appropriate
      antibiotic. Plesiomonas shigelloides should be added to the list of microbial
      agents associated with polyarthritis.

PMID- 8533053
TI  - Perceptual unit formation in simple motion patterns.
AB  - The present study investigated the proximal constraints that determine perceptual
      unit formation under minimal stimulus conditions. Projections of three moving
      dots, which could form two possible two-dot configurations, were presented to
      naive observers. In a forced-choice situation, their task was to report which two
      dot configuration was perceived as a distinct perceptual unit. The results showed
      that common motions (arbitrary translations and rigid rotations in the
      frontoparallel plane) have stronger grouping as compared to different relative
      motions (expansion/contractions, or simultaneous expansions/contractions and
      deformations in the frontoparallel plane). It was found that proximal changes of
      distances between elements in two-dot structures reduce grouping power. Changes
      of proximal directions, however, did not affect unit formation in two-dot
      structures at all. The effect of vector algebraic combinations on grouping power
      in three-dot structures was also investigated. Evidently, visual vector analysis
      splits up motion combinations into their constituents, and in some cases this
      contributes to additive effects.

PMID- 8533054
TI  - Immune disorders and handedness in dyslexic boys and their relatives.
AB  - Thirty dyslexic and 30 control boys aged 7-11 years were compared for frequency
      of immune disorders and handedness as well as for family history of immune
      disorders and learning disabilities (dyslexia and stuttering). They were also
      compared for neurological status and for history of speech and language
      difficulties. There were no significant differences between the two groups in the
      frequency of immune disorders and in handedness. The results showed significantly
      more dyslexic boys with soft neurological signs and signs of speech and language
      disorders. The frequency of dyslexia was significantly higher in the relatives of
      the dyslexic boys. Also significantly more mothers of the dyslexic boys reported
      difficulties during pregnancy and complications at delivery. The results are
      discussed in terms of Geschwind's hypothesis and neuromaturational delay as
      possible determinants of developmental dyslexia.

PMID- 8533055
TI  - On stability of the structure of implicit personality theory over situations.
AB  - In the present study, the following (hitherto unaddressed) question was posed:
      "Is the structure of implicit personality theory stable over situations?". In
      order to answer this question, correlation coefficients were computed between
      different aspects of two trait-structures obtained under different situational
      conditions. The results seem to indicate that the structure of IPT is stable over
      situations. The results are discussed in the light of some methodological
      considerations.

PMID- 8533056
TI  - [The validity of oculomotor laws].
AB  - The three-dimensional search coil technique provides a tool to dynamically study
      the laws on ocular cyclotorsion, which have already been formulated for the
      static situation, i.e. visual fixations, around 1850. Precise eye movement
      recordings show that Donders' law and Listing's law can even be violated under
      physiological conditions, e.g. during saccades. Conversely, experimental lesions
      of the mesencephalic vertical-torsional pulse generator only lead to small
      disturbances of Listing's law. Case studies of patients with torsional eye
      movement disorders indicate that a number of different vestibular and ocular
      motor pathologies can lead to violations of Listing's law.

PMID- 8533057
TI  - [Hereditary motor and sensory neuropathies. Clinical and molecular genetic
      aspects].
AB  - Hereditary motor sensory neuropathies are a heterogeneous group of inherited
      diseases of the peripheral nerves. In this review the clinical and genetic
      differences between the sub-groups of this disease will be discussed. Since the
      discovery of a 1.5 mb duplication on chromosome 17 p11.2-12 in most patients with
      a hereditary motor sensory neuropathy and a variety of different mutations on
      chromosomes 1 and X in other patients with a similar disease profile, Dycks'
      clinical classification needs to be re-evaluated. In this review Dycks' taxonomy
      of heridihary neuropathies will be compared to a new genetic classification and a
      relevant diagnostic procedure proposed when a hereditary neuropathy is suspected.

PMID- 8533058
TI  - [Therapy of epilepsy: trends and effectiveness of new anticonvulsants].
AB  - New antiepileptic drugs such as vigabatrin, lamotrigine, gabapentin,
      oxcarbazepine and felbamate have been lately marketed. This article provides an
      overview, showing known modes of action, pharmacokinetics, efficacy,
      tolerability, interactions and indications. A table showing selected data of
      antiepileptic drugs is included.

PMID- 8533059
TI  - [Initial symptomatology of Parkinson disease].
AB  - The early diagnosis of Parkinson's disease (idiopathic parkinsonism) is important
      for two reasons. Some never drugs possibly have a neuroprotective effect, which
      can be utilized maximally only with early onset of treatment. Moreover,
      diagnostic mistakes may occur early in the course of the disease. Although the
      hallmark of Parkinson's disease is a syndrome of movement disorders, slight
      cognitive deficits, depression, or pain with or without paresthesias can be
      present at an early stage. Therefore, symptoms at the time of the first diagnosis
      and at the beginning of the first clinical manifestation of Parkinson's disease
      are often not identical. The diagnosis can be made only clinically, since no
      biological marker is available up to now. However, in unclear cases
      pharmacological tests constitute a valuable extension of the clinical
      examination.

PMID- 8533060
TI  - [Recurrent Miller Fisher syndrome. Significance of anti-GQ1B antibodies].
AB  - In the present report, an unusual case of recurrent Miller Fisher syndrome is
      described. The patient presented within ten years three similar episodes of
      ophthalmoplegia, ataxia and areflexia associated with oropharyngeal weakness and
      signs of mild distal sensory neuropathy. An elevated titer of anti-GQ1b
      ganglioside antibodies correlated well with the clinical symptoms and signs. The
      pathogenic role of these antibodies in Miller Fisher syndrome is discussed.

PMID- 8533062
TI  - Resisting resistance. Experts worldwide mobilize against drug-resistant germs.

PMID- 8533061
TI  - AIDS concerns.

PMID- 8533063
TI  - Colorectal cancer mortality among men.

PMID- 8533064
TI  - The world according to RNA. Experiments lend support to the leading theory of
      life's origin.

PMID- 8533065
TI  - Caloric restriction and aging.

PMID- 8533066
TI  - Neural networks for vertebrate locomotion.

PMID- 8533067
TI  - Bacterial genetic exchange in nature.
AB  - Most bacteria are haploid organisms containing only one copy of each gene per
      cell for most of the growth cycle. This means that the chance for correcting
      random mutations in bacterial genes would depend entirely on the complementarity
      inherent in DNA structures, unless homologous DNA sequences can be imported from
      outside the cell. Bacteria, like all living organisms have evolved at least one
      autonomous mechanism, conjugation, for exchanging portions of genetic materials
      between two related cells. The ecological benefits of conjugation include the
      expansion of metabolic versatility and resistance to hazardous environmental
      conditions. Natural bacterial genetic exchange also occurs through virus
      infections (transduction) and through the uptake of extracellular DNA
      (transformation). The origin and ecological benefits of transduction and
      transformation are difficult to assess because they are driven by factors
      external to the affected cell. Bacterial genetic exchange has implications for
      the evolution of phenotypes that are either beneficial to humans, such as
      biodegradation of toxic xenobiotic chemicals, or that are detrimental, such as
      the evolution of pathogenesis and the spread of antibiotic resistance.
      Understanding natural bacterial genetic exchange mechanisms is also relevant to
      the assessment of dispersal risks associated with genetically engineered bacteria
      and recombinant genes in the environment.

PMID- 8533068
TI  - Transmissibility of Creutzfeldt-Jakob disease and related disorders.
AB  - The spongiform encephalopathies occur in both animals and humans, with kuru,
      Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, and Fatal
      Familial Insomnia constituting the currently recognised spectrum of such
      disorders in man. All have proven to be transmissible, including familial cases.
      Important determinants of transmissibility include the route of inoculation
      (intracerebral is most effective) and the titre of the inoculated material (brain
      and spinal cord have greatest infectivity). However, in familial cases, the
      pathogenic mutations in the PrP gene additionally influence the efficacy of
      transmission. Recent progress in the molecular biological basis of these diseases
      suggests that most of the infectivity resides in an abnormal, relatively protease
      resistant, isoform of the constitutively expressed PrP. The abnormal isoform is
      postulated to serve as a template for auto-catalytic polymerisation and the
      consequent deposition of amyloid. Extensions of this hypothesis attempt to
      reconcile the paradox of how these disorders can be both infectious and also
      inherited in an autosomal dominant fashion.

PMID- 8533069
TI  - [Results of a study of quality control of diagnostic ultrasound equipment].
AB  - AIMS: In this paper results of a quality control programme for B-mode ultrasound
      equipment used in clinical routine are presented. Over a period of 18 months 5
      modern scanners with altogether 19 scanheads were periodically controlled.
      METHODS: The methods used for measuring the various performance parameters of an
      ultrasound equipment followed closely standard methods. All measurements were
      carried out with commercially available tissue-mimicking phantoms, and documented
      in a uniform protocol. RESULTS: Based on the results it was found that 11 of the
      scanheads did not operate correctly; 2 additional ones were severely defective.
      Only 6 scanheads were without loss of image quality or function. For the 13
      malfunctioning scanheads adjustments, repair or even an exchange was necessary.
      CONCLUSION: The study demonstrates that quality control performed periodically is
      necessary to ensure optimal image quality and safe operation of the equipment.

PMID- 8533070
TI  - [Ultrasound differential diagnostic aspects in cystadenoma of the pancreas].
AB  - AIM: Assessment of differential diagnostic criteria of cystic adenomas of the
      pancreas. METHOD: We rechecked on all diagnostic criteria of patients with
      pancreatic pseudocysts retrospectively who had been treated in our department
      between 1981 and 1993. RESULTS: 12 patients with cystic adenomas of the pancreas
      had been treated in our department i.a. 7.8% of all cystic pancreatic tumours.
      Histopathologically 1 microcystic and 4 macrocystic adenomas as well as 7 cystic
      adenocarcinomas were seen. CONCLUSION: Diagnostic ultrasound criteria are
      discussed. Ultrasound-guided fine--needle-biopsy (FNB) is necessary to diagnose
      the content as well as the status of the pancreatic cysts. The ultrasound and the
      fine-needle-biopsy findings are important for differentiating between cystic
      adenomas and pseudocysts of the pancreas.

PMID- 8533071
TI  - [Percutaneous ultrasound-guided fine needle puncture of parasitic liver cysts:
      risks and benefits].
AB  - AIM: Percutaneous drainage (PD) has been used successfully in the percutaneous
      drainage of hepatic hydatid cysts in spite of discouragement by some authors from
      potential complications such as anaphylactic shock or seeding due to spillage.
      The aim of this meta-analysis was to evaluate the safety and efficacy of this new
      form of treatment and to develop a rational approach to the management of liver
      hydatosis by ultrasound guided PD. METHOD: Relevant articles published in
      English, French and German from 1983 to 1993 were identified through a computer
      search of data on the clinical manifestations, complications, anthelmintic
      treatment in combination with PD and on recurrence rate. RESULTS: 104 hydatid
      cysts treated by US-guided PD were published in literature. In 25% of the cases
      diagnosis was unsuspected prior to PD. None of these patients developed serious
      complications. All symptomatic patients were relieved of symptoms. None of the
      patients needed surgery. The complication rate was 14.4% and mortality was zero.
      Anthelmintic drug treatment in combination with PD showed no reduction of side
      effects. No recurrences were reported during follow-up (3-31 months). CONCLUSION:
      With proper patient monitoring US-guided PD can be recommended as a routine
      diagnostic and therapeutic tool in liver hydatosis.

PMID- 8533072
TI  - [Endosonography in diagnosis of insulinoma].
AB  - AIM: In a prospective study endoscopic ultrasonic localisation of clinically
      suspected insulinomas was compared with the findings of abdominal ultrasound,
      computed tomography and magnetic resonance imaging. METHOD: From Dec. 1990 to
      Jan. 1995 11 patients (8f, 3m, median age 42 [27-79] years) were enrolled in the
      study. The preoperative endosonographic findings were compared to surgery (n = 7)
      or clinical follow-up (n = 4). RESULTS: Endoscopic ultrasound identified a
      solitary tumour (mean size 12.4 mm) in 7 of 11 patients, which was proven at
      surgery in 5 patients and by transhepatic portal venous sampling after negative
      partial pancreas resection in 1 patient. One patient is still awaiting surgery.
      Clinical follow-up (n = 2) and negative intraoperative and histological findings
      of partial pancreas resection (n = 1) confirmed a true negative examination in 3
      patients. One patient with negative endoscopic ultrasound is still under
      medication for recurrent hypoglyctemia. Abdominal ultrasound (n = 11), computed
      tomography (n = 11) and magnetic resonance imaging (n = 5) were negative in all
      investigated patients. CONCLUSION: Endoscopic ultrasound is highly accurate for
      localisation of insulinomas and should be performed early in the preoperative
      management of these patients.

PMID- 8533073
TI  - [Color-coded duplex ultrasound of the vertebral artery: normal findings and
      pathologic findings in obstruction of the vertebral artery and remaining cerebral
      arteries].
AB  - AIM: The aim of this study was to determine normal values of flow velocities in
      the extracranial vertebral artery (VA) with regard to diameter of the VA, blood
      pressure and age. Hemodynamic changes in the VA in occlusive disease of the brain
      supplying arteries were also to be investigated. Based on the findings the
      clinical value of CCDS for the investigation of the VA were to be assessed.
      METHOD: The evaluation was carried out by a CCDS-scanner with a 7.5 MHz
      transducer in 85 normal individuals and in 166 patients with occlusive disease of
      the cerebral arteries. RESULTS: The average maximal systolic flow velocity was 59
      +/- 17, time averaged maximal velocity 31 +/- 10 and enddiastolic velocity 19 +/-
      8 cm/sec. Significantly reduced flow velocities were found in severely stenosed
      and in occluded VA increased flow velocities in VA serving as collateral pathway
      in higher grade obstructions of contralateral VA, ICA, and SCA. CONCLUSION: CCDS
      of the VA is a valuable tool in diagnosis of severe obstructions of the VA, but
      also for demonstration of collateral flow. Furthermore, cervical collateral
      pathways in severe obstruction of the VA-origin can be detected. Diagnosis of
      moderate stenosis of the ostium of the VA remains difficult.

PMID- 8533074
TI  - [Changes in pulsatility of the middle cerebral artery during the hyperemic phase
      after carotid compression. Studies with simultaneous bilateral transcranial
      Doppler].
AB  - AIM: The aim of the present study was to investigate the hypothesis that the
      transient hyperaemic response (THR), i.e. the TCD measured increase in MCA blood
      flow velocity, indicate an intact cerebral autoregulation. METHOD: THR tests were
      performed repeatedly in 6 healthy volunteers during simultaneous bilateral TCD
      recording of the MCA Doppler spectrum. The changes in the pulsatility index (PI)
      and the pulsatility transmission index (PTI) during the THR were compared with
      their baseline values. RESULTS: THR was observed in all subjects on each side.
      PTI of the MCA decreased during the THR. PI did not change on the side of carotid
      compression, but increased in the contralateral MCA. CONCLUSION: The results
      suggest that the cerebrovascular resistance is decreased during the THR and that
      the THR indicates a functioning cerebral autoregulation. While PI is strongly
      influenced by upstream haemodynamic forces, PTI seems to be an indicator of
      cerebrovascular resistance downstream to the sample volume.

PMID- 8533075
TI  - [Ultrasound diagnosis of epignathus in the 17th week of pregnancy. Case report
      and review of the literature].
AB  - An epignathus was found by routine screening ultrasound examination in the 17th
      week of pregnancy. Epignathi are teratomas in the oral cavity and are rarely
      found. The detection of an epignathus in the first half of pregnancy was
      described only three times in literature. The teratoma may also invade the
      cerebrum and is associated with a polyhydramnios and elevated alphafetoprotein.
      If the diagnosis is made in the first half of pregnancy a induced abortion is to
      be discussed.

PMID- 8533076
TI  - Animal testing and EPA.

PMID- 8533077
TI  - Suit alleges misuse of peer review.

PMID- 8533078
TI  - Planning for the next flu pandemic.

PMID- 8533079
TI  - Institute of Medicine. Panel to Feds: hands off radioisotopes.

PMID- 8533080
TI  - A new guide to the human genome.

PMID- 8533081
TI  - Search for better crystals explores inner, outer space.

PMID- 8533082
TI  - Novel center seeks to add spark to origins of life.

PMID- 8533083
TI  - The myth of Eve: molecular biology and human origins.
AB  - It has been proposed that modern humans descended from a single woman, the
      "mitochondrial Eve" who lived in Africa 100,000 to 200,000 years ago. The human
      immune system DRB1 genes are extremely polymorphic, with gene lineages that
      coalesce into an ancestor who lived around 60 million years ago, a time before
      the divergence of the apes from the Old World monkeys. The theory of gene
      coalescence suggests that, throughout the last 60 million years, human ancestral
      populations had an effective size of 100,000 individuals or greater. Molecular
      evolution data favor the African origin of modern humans, but the weight of the
      evidence is against a population bottleneck before their emergence. The
      mitochondrial Eve hypothesis emanates from a confusion between gene genealogies
      and individual genealogies.

PMID- 8533084
TI  - Medfly transformed--official!

PMID- 8533085
TI  - Plasmodesmata: plant channels for molecules on the move.

PMID- 8533086
TI  - An STS-based map of the human genome.
AB  - A physical map has been constructed of the human genome containing 15,086
      sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The
      project involved assembly of a radiation hybrid map of the human genome
      containing 6193 loci and incorporated a genetic linkage map of the human genome
      containing 5264 loci. This information was combined with the results of STS
      content screening of 10,850 loci against a yeast artificial chromosome library to
      produce an integrated map, anchored by the radiation hybrid and genetic maps. The
      map provides radiation hybrid coverage of 99 percent and physical coverage of 94
      percent of the human genome. The map also represents an early step in an
      international project to generate a transcript map of the human genome, with more
      than 3235 expressed sequences localized. The STSs in the map provide a scaffold
      for initiating large-scale sequencing of the human genome.

PMID- 8533087
TI  - Direct perception of three-dimensional motion from patterns of visual motion.
AB  - Measurements of retinal motion along a set of predetermined orientations on the
      retina of a moving system give rise to global patterns. Because the form and
      location of these patterns depend purely on three-dimensional (3D) motion, the
      effects of 3D motion and scene structure on image motion can be globally
      separated. The patterns are founded on easily derivable image measurements that
      depend only on the sign of image motion and do not require information about
      optical flow. The computational theory presented here explains how the self
      motion of a system can be estimated by locating these patterns.

PMID- 8533088
TI  - Selective trafficking of KNOTTED1 homeodomain protein and its mRNA through
      plasmodesmata.
AB  - Plasmodesmata are intercellular organelles in plants that establish cytoplasmic
      continuity between neighboring cells. Microinjection studies showed that
      plasmodesmata facilitate the cell-to-cell transport of a plant-encoded
      transcription factor, KNOTTED1 (KN1). KN1 can also mediate the selective
      plasmodesmal trafficking of kn1 sense RNA. The emerging picture of plant
      development suggests that cell fate is determined at least in part by
      supracellular controls responding to cellular position as well as lineage. One of
      the mechanisms that enables the necessary intercellular communication appears to
      involve transfer of informational molecules (proteins and RNA) through
      plasmodesmata.

PMID- 8533089
TI  - Interaction of tobamovirus movement proteins with the plant cytoskeleton.
AB  - The movement protein of tobacco mosaic tobamovirus and related viruses is
      essential for the cell-to-cell spread of infection and, in part, determines the
      host range of the virus. Movement protein (MP) was fused with the jellyfish green
      fluorescent protein (GFP), and a modified virus that contained this MP:GFP fusion
      protein retained infectivity. In protoplasts and leaf tissues, the MP:GFP fusion
      protein was detected as long filaments shortly after infection. Double-labeling
      fluorescence microscopy suggests that the MP interacts and coaligns with
      microtubules. The distribution of the MP is disrupted by treatments that disrupt
      microtubules, but not by cytochalasin B, which disrupts filamentous F-actin.
      Microtubules may target the MP to plasmodesmata, the intercellular channels that
      connect adjacent cells.

PMID- 8533090
TI  - Tobacco MAP kinase: a possible mediator in wound signal transduction pathways.
AB  - A complementary DNA encoding a mitogen-activated protein (MAP) kinase homolog has
      been isolated from tobacco plants. Transcripts of the corresponding gene were not
      observed in healthy tobacco leaves but began to accumulate 1 minute after
      mechanical wounding. In tobacco plants transformed with the cloned complementary
      DNA, trans inactivation of the endogenous homologous gene occurred, and both
      production of wound-induced jasmonic acid and accumulation of wound-inducible
      gene transcripts were inhibited. In contrast, the levels of salicylic acid and
      transcripts for pathogen-inducible, acidic pathogenesis-related proteins were
      increased upon wounding. These results indicate that this MAP kinase is part of
      the initial response of higher plants to mechanical wounding.

PMID- 8533091
TI  - Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor
      learning.
AB  - The cerebellar cortex is implicated in the learning of complex motor skills. This
      learning may require synaptic remodeling of Purkinje cell inputs. An
      extracellular serine protease, tissue plasminogen activator (tPA), is involved in
      remodeling various nonneural tissues and is associated with developing and
      regenerating neurons. In situ hybridization showed that expression of tPA
      messenger RNA was increased in the Purkinje neurons of rats within an hour of
      their being trained for a complex motor task. Antibody to tPA also showed the
      induction of tPA protein associated with cerebellar Purkinje cells. Thus, the
      induction of tPA during motor learning may play a role in activity-dependent
      synaptic plasticity.

PMID- 8533092
TI  - A subclass of bHLH proteins required for cardiac morphogenesis.
AB  - Skeletal muscle development is controlled by a family of muscle-specific basic
      helix-loop-helix (bHLH) transcription factors. Two bHLH genes, dHAND and eHAND,
      have now been isolated that are expressed in the bilateral heart primordia and
      subsequently throughout the primitive tubular heart and its derivatives during
      chick and mouse embryogenesis. Incubation of stage 8 chick embryos with dHAND and
      eHAND antisense oligonucleotides revealed that either oligonucleotide alone had
      no effect on embryonic development, whereas together they arrested development at
      the looping heart tube stage. Thus, dHAND and eHAND may play redundant roles in
      the regulation of the morphogenetic events of vertebrate heart development.

PMID- 8533093
TI  - The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex
      localization.
AB  - Hydrolysis of guanosine triphosphate (GTP) by the small guanosine triphosphatase
      (GTPase) adenosine diphosphate ribosylation factor-1 (ARF1) depends on a GTPase
      activating protein (GAP). A complementary DNA encoding the ARF1 GAP was cloned
      from rat liver and predicts a protein with a zinc finger motif near the amino
      terminus. The GAP function required an intact zinc finger and additional amino
      terminal residues. The ARF1 GAP was localized to the Golgi complex and was
      redistributed into a cytosolic pattern when cells were treated with brefeldin A,
      a drug that prevents ARF1-dependent association of coat proteins with the Golgi.
      Thus, the GAP is likely to be recruited to the Golgi by an ARF1-dependent
      mechanism.

PMID- 8533094
TI  - Gene transfer into the medfly, Ceratitis capitata, with a Drosophila hydei
      transposable element.
AB  - Exogenous functional DNA was introduced into the germline chromosomes of the
      Mediterranean fruit fly (medfly) Ceratitis capitata with a germline
      transformation system based on the transposable element Minos from Drosophila
      hydei. Transformants were identified as phenotypic revertants of a white-eyed
      mutation carried by the recipient strain. Clusters of transformants were detected
      among the progeny of 390 individuals screened for germline transformation. Five
      independent and phenotypically active integration events were identified, in each
      of which a single copy of the transposon was inserted into a different site of
      the medfly genome. Molecular analysis indicates that they represent transposase
      mediated insertions of the transposon into medfly chromosomes.

PMID- 8533095
TI  - The white gene of Ceratitis capitata: a phenotypic marker for germline
      transformation.
AB  - Reliable germline transformation is required for molecular studies and ultimately
      for genetic control of economically important insects, such as the Mediterranean
      fruit fly (medfly) Ceratitis capitata. A prerequisite for the establishment and
      maintenance of transformant lines is selectable or phenotypically dominant
      markers. To this end, a complementary DNA clone derived from the medfly white
      gene was isolated, which showed substantial similarity to white genes in
      Drosophila melanogaster and other Diptera. It is correlated with a spontaneous
      mutation causing white eyes in the medfly and can be used to restore partial eye
      color in transgenic Drosophila carrying a null mutation in the endogenous white
      gene.

PMID- 8533096
TI  - Identification of a member of the MAPKKK family as a potential mediator of TGF
      beta signal transduction.
AB  - The mitogen-activated protein kinase (MAPK) pathway is a conserved eukaryotic
      signaling module that converts receptor signals into various outputs. MAPK is
      activated through phosphorylation by MAPK kinase (MAPKK), which is first
      activated by MAPKK kinase (MAPKKK). A genetic selection based on a MAPK pathway
      in yeast was used to identify a mouse protein kinase (TAK1) distinct from other
      members of the MAPKKK family. TAK1 was shown to participate in regulation of
      transcription by transforming growth factor-beta (TGF-beta). Furthermore, kinase
      activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic
      protein. These results suggest that TAK1 functions as a mediator in the signaling
      pathway of TGF-beta superfamily members.

PMID- 8533097
TI  - Age of bacteria from amber.

PMID- 8533098
TI  - Age of bacteria from amber.

PMID- 8533099
TI  - The effect of sodium salicylate and aspirin on NF-kappa B.

PMID- 8533100
TI  - Neurotrophins and excitotoxicity.

PMID- 8533101
TI  - Newer visual function tests in the evaluation of glaucoma.
AB  - Conventional visual field testing, with a uniform white-on-white stimulus, is
      used routinely to diagnose and follow patients with chronic open-angle glaucoma.
      Many investigators, however, believe that conventional perimetry may not detect
      the earliest visual dysfunction in patients with chronic open-angle glaucoma.
      Consequently, much research has been performed over the past decade to develop a
      visual function test which might diagnose chronic open-angle glaucoma earlier
      than conventional perimetry. This review discusses the mechanisms, clinical
      studies and the current usefulness of the most common new visual function
      techniques. These tests attempt to detect early glaucomatous visual loss,
      generally by placing the visual system under stress and by minimizing the
      influence of extensive functional redundancy in the retinal ganglion cell network
      due to widely overlapping receptive fields. Success of new visual function tests
      depends on the specificity and the sensitivity of the instrument, excellent
      patient acceptance, short test duration, standardization of techniques, and
      limited expense. In addition to searching for newer visual function tests to
      evaluate glaucoma, we should continue efforts to improve the diagnostic
      capability and shorten the test duration of conventional perimetry.

PMID- 8533102
TI  - Melanocytoma of the iris with rapidly developing secondary glaucoma.
AB  - A 28-year-old woman with an upper nasal iris mass developed secondary glaucoma
      within a few months of presentation. Although the elevated pressure responded to
      medical therapy, in the interests of a definitive diagnosis as well as prevention
      of damage to the trabecular meshwork, surgical management was decided upon. Tumor
      excision was performed through a double-layered sclerolimbal flap. Light and
      electron microscopic examinations of the tissue revealed a partially necrotic
      iris melanocytoma. Six months after surgery, the patient's best corrected visual
      acuity was 20/30 in the affected eye, and the intraocular pressure was 21 mmHg
      without therapy. The lens remained clear. The differential diagnosis and
      management of melanocytomas, particularly the role of biopsy, are discussed.

PMID- 8533103
TI  - Retinal artery occlusion.
AB  - A 54-year-old man presented with an acute painless loss of vision. He had a three
      month history of malaise, weight loss, and episodic sweating. Physical
      examination showed a thin, febrile man with a petechial rash over the lower legs.
      Cardiac auscultation revealed an apical thrill and pansystolic murmur. Dental
      hygiene was poor. The diagnosis, mechanisms and treatment of retinal artery
      occlusion associated with bacterial endocarditis are reviewed.

PMID- 8533104
TI  - Non-ophthalmologic findings of the Diabetes Control and Complications Trial.
AB  - The Diabetes Control and Complications Trial (DCCT) was a large and rigorously
      conducted trial which definitively established that longterm hyperglycemia causes
      longterm diabetic complications. In this review the author considers the non
      ophthalmologic results of the DCCT and the applications of these findings to
      current and future care of diabetic patients. It is concluded that people with
      diabetes do not need to anticipate a future of diabetic complications, and that
      improved glycemic control can be achieved through the education and cooperation
      of physicians, patients, and health care payers.

PMID- 8533105
TI  - A history of primary angle closure glaucoma.
AB  - The satisfactory control and cure of attacks of primary angle closure glaucoma
      spans one hundred years following von Graefe's iridectomy in 1856. Gonioscopy was
      required to validate the theories of shallow anterior chamber and pupillary
      obstruction, but the gonioscopists looked for the causes of angle closure in
      their own territory at the angle in the periphery of the anterior chamber and
      disregarded the center. General agreement of the importance of pupil block was
      thereby delayed for over ten years. Advances in pharmacology and the invention of
      laser surgery gave opthalmologists a comfortable control of a formerly
      distressing, blinding disease.

PMID- 8533106
TI  - Congenital optic disk anomalies.

PMID- 8533107
TI  - Excimer laser photorefractive keratectomy.
AB  - Excimer laser photorefractive keratectomy has been used for the correction of
      myopia, hyperopia and astigmatism. This laser removes tissue through a process
      termed photoablative decomposition, in which incident photon energy is sufficient
      to break molecular bonds. Selective removal of tissue across the anterior corneal
      surface results in a change in anterior corneal curvature. The surgical outcome
      may be influenced also by interindividual variability in wound healing and
      pharmacologic interventions. The nature of the excimer laser-tissue interaction,
      and clinical outcomes of predictability, stability and complications of surgery
      for myopia are discussed in detail.

PMID- 8533108
TI  - Ethylene glycol ethers.

PMID- 8533109
TI  - Descriptive epidemiology of alimentary tract atresia.
AB  - A study has been made on certain epidemiological characteristics of infants with
      alimentary tract atresia: esophageal atresia, small and large gut atresia, and
      anal atresia. Data were collected from three malformation registries and
      represent a material of more than 4.5 million births. A total of 3,550 infants
      with alimentary atresia were identified corresponding to a total rate of about 8
      per 10,000 births. In 167 infants (4.7%) more than one of the major atresia types
      were present simultaneously. Racial differences were found (based on data from
      California) for esophageal atresia where whites had a higher rate than other
      races. For gastrointestinal atresia, a high rate in blacks was found, while no
      differences between races were seen for anal atresia. Also, differences in
      registered rates between the three programs were found, at least partly
      explainable by different ascertainment. The different forms of atresia were
      compared from the point of view of sex ratio, twinning rate, maternal age and
      parity distribution, presence of chromosome anomalies, and types of associated
      malformations. The pathogenesis and etiology of the various types of atresia are
      discussed based on these observations. The conclusion is that although
      undoubtedly other pathogenetic mechanisms may exist for gastrointestinal atresia,
      a substantial proportion of all infants with alimentary atresia had their
      malformations as a result of early disturbances of intestinal morphogenesis.
      Within each subgroup, apparently different etiologies may exist, resulting in
      differences in epidemiological characteristics.

PMID- 8533110
TI  - Induction of apoptosis and cathepsin D in limbs exposed in vitro to an activated
      analog of cyclophosphamide.
AB  - Apoptosis, a form of active cell death, plays a role during normal limb
      development. The present study was done to test the hypothesis that the teratogen
      cyclophosphamide, an alkylating agent and commonly used anticancer drug, produces
      malformations by disturbing the regulation of apoptosis in the limb. The effects
      of a preactivated analog of cyclophosphamide, 4-hydroperoxycyclophosphamide, on
      limb development and on apoptosis in the limb were determined in vitro. Cathepsin
      D is a lysosomal protease which is induced in tissues undergoing destruction by
      apoptosis. To further examine the process of apoptosis in the limb, the effects
      of 4-hydroperoxycyclophosphamide exposure on cathepsin D protein concentration
      and on the immunolocalization of cathepsin D in limb buds were assessed. Limb
      buds from gestational day 12 mice were excised and cultured in roller bottles in
      a chemically defined medium for up to 6 days. The addition of 4
      hydroperoxycyclophosphamide (1 or 10 micrograms/ml) to the culture medium
      produced time- and concentration-dependent limb malformations. Electrophoresis of
      the DNA extracted from both control and treated limbs revealed a DNA
      fragmentation pattern characteristic of apoptosis. Limbs cultured in the control
      medium showed a "DNA ladder" only after 72 hours in vitro; however, those in the
      drug-treated groups showed fragmentation within 12 hours of drug exposure.
      Acridine orange staining and examination of cell ultrastructure with the electron
      microscope further confirmed that apoptotic cell death in the interdigital areas
      was accelerated in drug-exposed limbs. The relative abundance of cathepsin D in
      limbs exposed to 4-hydroperoxycyclophosphamide for 24 hours was increased
      compared to control limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533111
TI  - Role of formate in methanol-induced exencephaly in CD-1 mice.
AB  - Mouse embryos develop exencephaly when dams are exposed by inhalation to high
      concentrations (> or = 10,000 ppm) of methanol on gestational day 8 (GD8;
      copulation plug = GD0). The present study examined the role of formate, an
      oxidative metabolite of methanol, in the development of methanol-induced
      exencephaly in CD-1 mice and cultured mouse embryos. The pharmacokinetics and
      developmental toxicity of sodium formate (750 mg/kg by gavage), a 6-hr methanol
      inhalation (10,000 or 15,000 ppm), or methanol gavage (1.5 g/kg) in pregnant CD-1
      mice on GD8 were determined. Gross morphological evaluations for neural tube
      closure status in embryos or exencephaly in near-term fetuses were performed.
      Decidual swellings and maternal plasma were analyzed for methanol and formate.
      The mean (+/- S.E.M.) end-of-exposure plasma methanol concentration was 223 +/-
      23 mM following the 6-hr, 15,000 ppm methanol inhalation. There were no changes
      in blood or decidual swelling formate concentrations under any of the methanol
      exposure conditions. Peak formate levels in plasma (1.05 +/- 0.2 mM; control 0.5
      +/- 0.3 mM) and decidual swelling (2.0 +/- 0.2 mM; control 1.1 +/- 0.2 mM) from
      pregnant mice (GD8) given sodium formate (750 mg/kg, po) were similar to those
      observed following a 6-hr methanol inhalation of 15,000 ppm (plasma = 0.75 +/-
      0.1 mM; decidual swelling = 2.2 +/- 0.3 mM) but did not result in
      exencephaly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533112
TI  - Clusterin expression during programmed and teratogen-induced cell death in the
      postimplantation rat embryo.
AB  - Clusterin appears to play a role in multiple cellular processes including
      reproductive cell function, lipid transport, complement regulation, and endocrine
      secretion. In addition, clusterin has been shown to be associated with both
      developmental and induced cell death. We have used immunohistochemistry and in
      situ hybridization to study the relationship between clusterin expression, normal
      programmed cell death (PCD) in the developing rat limb bud, and abnormal cell
      death induced by hyperthermia in day 11 rat embryos. Immunohistochemical
      localization of clusterin in day 14-16 limb buds showed that the most intense
      immunostaining was associated with the condensing mesenchyme of the developing
      digit, a tissue exhibiting low levels of PCD. Moreover, areas of digital cell
      death, confined to future interphalangeal spaces, were devoid of clusterin
      immunostaining. Clusterin immunostaining was also observed in the interdigital
      mesenchyme and partially overlapped the cell death that occurs in this tissue
      during the early development of the digits. Although clusterin immunostaining
      overlaps areas of interdigital cell death, most apoptotic cells in the
      interdigital mesenchyme and underlying the surface ectoderm were not associated
      with clusterin immunostaining. We also examined the expression of clusterin in
      day 11 rat embryos exposed to 43 degrees C, an exposure that induces extensive
      cell death primarily in the developing neuroepithelium. In control embryos
      cultured at 37 degrees C, clusterin mRNA and protein were expressed at high
      levels in the heart, a tissue that is completely resistant to the cytotoxic
      effects of hyperthermia. Within 2.5 hr after an exposure of 43 degrees C,
      clusterin mRNA showed a dramatic induction in the prosencephalic mesenchyme and
      only a modest induction in the prosencephalic neuroepithelium.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8533113
TI  - Method and methodology in medical ethics: inaugurating another new section.
AB  - This essay announces the inauguration of a section of Theoretical Medicine and
      invites submissions on the topic "Method and Methodology in Medical Ethics." It
      offers some sketches of plausible meanings of "method" and "methodology" and
      their relationships as these might apply to work in biomedical ethics. It
      suggests a broad range of issues, dilemmas or conflicts that may be addressed for
      help via method and/or methodology.

PMID- 8533114
TI  - Philip Roth's Patrimony: narrative and ethics in a case study.
AB  - I assess the ethical content of Philip Roth's account of his father's final years
      with, and death from a tumor. I apply this to criticisms of the nature and
      content of case reports in medicine. I also draw some implications about
      modernism, postmodernism and narrative understandings.

PMID- 8533115
TI  - Moral integrity and values in medicine: inaugurating a new section.

PMID- 8533116
TI  - Moral growth in medical students.
AB  - Although students bring to medical school a fairly well established value system,
      the potential for moral growth through the medical school environment and
      experience is substantial. The educational environment poses a succession of
      developmental and adaptive tasks to be accomplished. Several of these tasks are
      discussed her, tasks that are value-laden and involve, directly or indirectly,
      the interplay of ethical theory and practice. During the past quarter century,
      the two influences that have had the greatest impact on the moral growth and
      moral reasoning capacity of medical students have been the incorporation into the
      medical school curriculum of courses in medical humanities and the admission to
      medical school of an increasing number of female students. The female students
      have brought to medical school a level or dimension of moral reasoning (morality
      as care or responsibility for others) to augment the male students' focus on
      rights and justice considerations.

PMID- 8533118
TI  - British Thoracic Society winter meeting. London, 11-13 December 1995. Abstracts.

PMID- 8533117
TI  - Empirical and normative aspects of medical technology assessment. The case of
      reduced-size liver transplantations with living donors.
AB  - Medical technology assessment deals with the evaluation of novel or existing
      health care procedures. This paper addresses the interdependence between factual
      and normative issues, using the controversies about acceptability and
      desirability of reduced-size liver transplantations with living donors as
      example.

PMID- 8533119
TI  - Can phenytoin lower plasma fibrinogen concentrations?
AB  - A strong, independent and positive association between plasma fibrinogen
      concentrations and cardiovascular disease has been established. To determine if
      phenytoin lowers fibrinogen levels we measured plasma fibrinogen levels in a
      subset of participants enrolled in a randomized, placebo-controlled, double-blind
      clinical trial. Participants received placebo or 100 mg, 200 mg, or 300 mg/day of
      phenytoin for 14 weeks. Fifty-six subjects had post-treatment and 20 had pre- and
      post-treatment fibrinogen measurements. The phenytoin-treated subjects with post
      treatment measurements had a 0.24 g/l (8%) reduction in mean fibrinogen levels
      compared to placebo (p = 0.3). Phenytoin may be capable of producing meaningful
      reductions in fibrinogen levels.

PMID- 8533120
TI  - Effect of fucoidan during activation of human plasminogen.
AB  - Fucoidan [sulfated poly (L-fucopyranose)] was compared with 6-aminohexanoic acid
      (6-AH) or CNBr-cleaved fibrinogen (CNBr-Fbg) alone or in combination in enhancing
      the activation of glutamic plasminogen (Glu-Plg) or lysine plasminogen (Lys-Plg)
      by two-chain tissue plasminogen activator (t-PA) or LMwt-urokinase or by
      streptokinase. Fucoidan enhanced the t-PA activation of Glu-Plg or Lys-Plg at Plg
      concentrations greater than 75nM, while stimulation by CNBr-Fbg of t-PA
      activation followed saturation kinetics of Michaelis-Menton. During t-PA
      activation of Glu-Plg, a high degree of synergism was observed between 6-AH and
      fucoidan while the enhancement by CNBr-Fbg was not influenced by fucoidan and was
      reversed by 6-AH. Fucoidan alone at higher concentrations was effective in
      enhancing the activation of Glu-Plg by urokinase while the combination of
      fucoidan and 6-AH showed additive effect in enhancing the activation of Lys-Plg.
      The activation of Glu-Plg by streptokinase was reversed by fucoidan in a manner
      similar to that reported for 6-AH. The results are interpreted to suggest that
      CNBr-Fbg and 6-AH compete with each other for the same lysine binding sites (LBS)
      on the Plg molecule while fucoidan acted synergistically with 6-AH in enhancing
      the t-PA activation of Glu-Plg by a different mechanism. The double reciprocal
      plot for the interaction of Glu-Plg and urokinase also showed a significantly
      higher affinity between the two in presence of fucoidan.

PMID- 8533121
TI  - Pharmacology of desmin (low molecular weight dermatan sulphate) in healthy
      volunteers following intravenous bolus administration of different dosages (200,
      400, 800 mg).
AB  - Eight healthy volunteers (6 males, 2 females, mean age 31.6 yrs), were
      administered--on three separate days--200, 400 and 800 mg of a new low molecular
      weight Dermatan sulphate (Desmin), given as a single i.v. bolus (2 min.)
      injection. Before each administration and 10, 20, 30 min., 1, 2, 4, 8, 12, 24
      hours after, blood samples were drawn and the following coagulative assays
      performed: aPTT (activated Partial Thromboplastin Time), TT (Thrombin Time), anti
      Xa (Xa Factor inhibition), Heptest, Stachrom D.S.. Furthermore, a kinetic
      analysis was performed on the activity curves calculated on the Heptest and
      Stachrom data. Plasma peak values and half lives of the parameters checked showed
      a clear dose-effect relationship. aPTT and TT showed very short-lasting
      variations and the inhibition of Factor Xa was moderate, but significant. The
      most evident and specific effects of Desmin were those on Heptest and Stachrom
      D.S.: both tests were influenced in a clear-cut and dose-dependent way, mainly as
      a consequence of the action of Desmin on HCII, with partially different kinetic
      patterns. A series of in vitro experiments proved an anti Xa effect of Desmin,
      mediated by antithrombin III, well above the possible interference of the small
      (< 1%) heparin contaminants in Desmin. An even more marked anti Xa activity was
      seen in the in vivo study, an observation so far unrecognized for this type of
      drug: some possible interpretations of this fact are discussed.

PMID- 8533122
TI  - Characterization of tumor-induced platelet aggregation: the role of immunorelated
      GPIb and GPIIb/IIIa expression by MCF-7 breast cancer cells.
AB  - Tumor cell induced platelet aggregation is thought to be an early step in the
      metastatic process. Here we show that platelet aggregation induced by MCF-7 cells
      is mediated, in part, through an ADP-dependent mechanism based on inhibition of
      aggregation by pretreatment of the tumor cells with apyrase and the
      identification of ADP in tumor cell-free supernatants by HPLC. By applying
      immunocytochemical and flow cytometric techniques, we demonstrate that platelet
      immunorelated glycoproteins, GPIb, GPIIb/IIIa, GPIb/IX, and the integrin alpha v
      subunit are expressed on the surface of MCF-7 cells. The expression of an
      immunorelated GPIb was further confirmed by immunoblot and autoradiography of
      125I-labelled MCF-7 cells. MCF-7 cell immunoblot preparations demonstrated one
      major protein reactive to an anti-GPIb alpha MoAb under nonreduced conditions
      with a molecular weight of 200 kD and two major proteins reactive with the anti
      GPIb alpha MoAb under reduced conditions with molecular weights of 92 kD and 38
      kD. Platelet aggregation is inhibited by preincubating the MCF-7 cells with
      antibodies to GPIb and GPIIb/IIIa. These findings document expression of adhesive
      glycoproteins by MCF-7 cancer cells and suggest that these receptors, together
      with ADP, play a role in tumor induced platelet aggregation.

PMID- 8533123
TI  - Performance characteristics and clinical evaluation of an in vitro bleeding time
      device--Thrombostat 4000.
AB  - The performance characteristics of an in vitro bleeding time device--Thrombostat
      4000 were evaluated and compared with the Simplate bleeding time in healthy
      individuals and patients with disorders of primary hemostasis. Reference ranges
      were established using 30 normal volunteers. Although there were variations
      between different filter batches, reproducibility was good within a single batch.
      There were no differences between the two channels of the instrument and between
      male and female subjects. Hematocrit correlated negatively with the initial flow
      (IF) and IF correlated positively with closure time (T) and bleeding volume (V).
      Aspirin could be detected only when the traditional addition of ADP was replaced
      with CaCl2. Both, closure time (T) or bleeding volume (V) were more sensitive
      than Simplate bleeding time and T was more sensitive than V in detecting patients
      with disorders of primary hemostasis. We conclude that the Thrombostat 4000 is a
      reproducible, reliable, sensitive and easy to use instrument. It is superior to
      the traditional in vivo bleeding times for investigations of disorders of primary
      hemostasis (screening, diagnosis, monitoring, etc.).

PMID- 8533124
TI  - The detection of lupus anticoagulant using the kaolin clotting time test: a
      comparative study of the different forms of analysis.
AB  - This work is a report of a comparative study between the different forms of
      analysis (curve, index, percentage and delta) of kaolin clotting time (KCT) for
      the detection of lupus anticoagulant. The reference values for all tests were
      defined from a study of 111 normal controls. 133 patients were studied, 106 with
      connective tissue disease and 27 with syphilis. LA was detected in 31 of the 133
      patients studied. For KCT, the percentage and the delta showed greater
      sensitivity (61% and 65%, respectively) as opposed to the curve and the index
      (48% and 26%, respectively). We found significant statistical differences between
      the frequency of positivity of the index and the delta (p < 0.001) and between
      the index and the percentage (p < 0.005). Our findings show that if it is
      necessary to use KCT as a complementary test for the detection of LA, then it is
      more convenient to carry it out by using the percentage or the delta forms of
      analysis.

PMID- 8533125
TI  - Effects of VLDL, chylomicrons, and chylomicron remnants on platelet
      aggregability.
AB  - Although influences of cholesterol-rich lipoproteins on platelet aggregation are
      well established, the knowledge of interactions between triglyceride-rich
      lipoproteins and platelets, in particular in the postprandial state, is limited
      and controversial. The in-vitro effects of these lipoproteins from
      hypertriglyceridemic subjects on the aggregation behavior of platelets from
      normolipemic donors were investigated with two whole-blood methods. VLDL and
      chylomicrons, but not chylomicron remnants, in concentrations comparable to
      concentrations occurring after a fatty meal, reduced platelet aggregation in a
      dose-dependent manner in particle counting. Impedance aggregometry failed to
      monitor these effects. We conclude, that triglyceride-rich lipoproteins inhibit
      platelet aggregation in vitro. They may, therefore, not be linked to the acute
      onset of myocardial infarction.

PMID- 8533126
TI  - Antiplatelet functions of a stable prostacyclin analog, SM-10906 are exerted by
      its inhibitory effect on inositol 1,4,5-trisphosphate production and cytosolic
      Ca++ increase in rat platelets stimulated by thrombin.
AB  - The mechanism of the antiplatelet functions of SM-10906, the active form of the 3
      oxa-methano-prostaglandin (PG) I1 analog SM-10902, was examined in rat platelets.
      SM-10906 activated adenylate cyclase in crude membrane fractions, and inhibited
      platelet aggregation and release of adenine nucleotides stimulated by thrombin.
      SM-10906 also inhibited malondialdehyde production induced by thrombin, but not
      that induced by arachidonic acid. This may account for its inhibitory effects on
      phospholipase A2. SM-10906 prevented thrombin-induced inositol 1,4,5
      trisphosphate production, Ca++ mobilization from intracellular Ca storage and
      45Ca++ influx into platelets, which were all reversed by pretreatment with the
      adenylate cyclase inhibitor 2',5'-dideoxyadenosine. PGI2 and PGE1 have the same
      antiplatelet profiles in the order of PGI2 > or = SM-10906 > PGE1. These results
      indicate that SM-10906 as well as PGI2 and PGE1 may exert antiplatelet activities
      by stimulating adenylate cyclase to prevent thrombin-induced phospholipase C and
      A2 activations and increase in cytosolic Ca++ level.

PMID- 8533127
TI  - Reduction of platelet surface GPIb expression induced by polymorphonuclear
      leukocytes.
AB  - It has been demonstrated that soluble factors released from PMNs such as
      proteases, free radicals and arachidonic acid metabolites are able to induce
      platelet activation (1). More recently, it has been demonstrated that PMNs can
      also inhibit platelet functional responses. It has been suggested that the
      inhibitory effect of PMNs could be related to the release of nitric oxide (NO) (2
      3). In contrast, we have previously observed that coincubation of platelets with
      unstimulated PMNs, results in the inhibition of platelet aggregation and ATP
      release by a yet non-identified mechanism that does not involves NO (4).
      Considering that an alteration in surface receptors could be one of the phenomena
      accounting for impaired platelet responses, in the present study we evaluated the
      ability of PMNs to modulate the expression of the glycoproteins (GP) involved in
      platelet adhesion and aggregation, GPIb-IX and GPIIb-IIIa.

PMID- 8533128
TI  - Effect of protamine on heparin releasable TFPI antigen levels in normal
      volunteers.

PMID- 8533129
TI  - von Willebrand factor antigen and fibronectin in essential hypertension.

PMID- 8533130
TI  - Renal blood flow, fibrinolysis, and platelet aggregation following tacrolimus (FK
      506) treatment in rats.

PMID- 8533131
TI  - [A horse with chronic eosinophilic enteritis].
AB  - A three-year-old pregnant Dutch Warmblood mare was referred to the Department of
      Large Animal Medicine and Nutrition, Faculty of Veterinary Medicine, because of
      weight loss for 1 month. The main clinical features were (beside weight loss)
      moderate ventral oedema, enlarged mesenteric lymph nodes, and uniform thickening
      of the wall of the jejunum. Haematological evaluation revealed leukocytosis (15.9
      G.l-1 with 18% lymphocytes and 1% eosinophils) and a decreased total serum
      protein and albumin concentration (35 g.l-1 and 36.3% albumin). At necropsy
      transmural eosinophilic enteritis was found in combination with macrophages.
      There was an abnormal (11% increase) absorption of glucose in the small
      intestine.

PMID- 8533132
TI  - [Salmonella dublin infections on a goat farm].
AB  - A Salmonella Dublin infection in young goats has been described. In a period of
      two weeks, 16 of 70 female-kids died within one day, because of septicaemia. Bad
      hygiene and management measures were discussed as the main reason for this
      outbreak.

PMID- 8533133
TI  - [The causative agent of PIA (porcine intestinal adenomatosis) can be demonstrated
      in swine manure via polymerase chain reaction (report of a demonstration].

PMID- 8533134
TI  - [Copper deficiency in newborn lambs].

PMID- 8533135
TI  - [Questions by practitioners in the field of ophthalmology].

PMID- 8533136
TI  - The sea anemone purine, caissarone: adenosine receptor antagonism.
AB  - Caissarone, a sea anemone iminopurine, produced an increase in the twitch
      response of the electrically stimulated guinea-pig ileum-myenteric plexus. In the
      same assay, caissarone reduced the inhibitory response to the endogenous
      neuromodulator, adenosine, the A1 adenosine receptor agonist, R
      phenylisopropyladenosine (R-PIA), and the A2 agonist, 5'-(N-cyclopropyl)
      carboxamidoadenosine (CPCA) in a dose-dependent manner. Schild plot analysis of
      antagonism by caissarone yielded slopes of near unity, indicating that caissarone
      acts as a simple competitive antagonist at the adenosine receptor. The
      dissociation constants (KB) for caissarone ranged from 0.53 mM to 0.78 mM. In
      functional nicotinic receptor assays in two human cell lines, caissarone failed
      either to potentiate or to reduce carbamylcholine-mediated 86Rb+ efflux. Thus,
      the enhancing activity of caissarone on the gut could not be attributed to
      activity at the ganglionic nicotinic receptor. Based on structure and
      pharmacological activity, caissarone appears to be the first marine product
      described as an adenosine receptor antagonist.

PMID- 8533137
TI  - Effects of stonustoxin (lethal factor from Synanceja horrida venom) on platelet
      aggregation.
AB  - Stonustoxin (SNTX) is a 148,000 mol. wt lethal factor isolated from Synanceja
      horrida venom. It induces species-restricted red cell haemolysis which correlates
      with its effects on platelet aggregation in whole blood. SNTX induced a
      concentration-dependent and irreversible platelet aggregation in rabbit or rat
      but not in human or mouse whole blood. The degree of haemolysis and platelet
      aggregation induced by SNTX in rabbit or rat whole blood were concentration
      dependent. At concentrations of SNTX where only slight or no haemolysis was
      observed, no platelet aggregation occurred. Although SNTX itself could not induce
      platelet aggregation in rabbit or rat platelet-rich plasma (PRP), it had biphasic
      effects on collagen- or ADP-induced platelet aggregation in PRP. It inhibited
      collagen- or ADP-induced platelet aggregation at high concentrations (0.08-0.8
      micrograms/ml) but the response was potentiated by lower stonustoxin
      concentrations (0.008-0.016 micrograms/ml). The inhibition of collagen- or ADP
      induced platelet aggregation might be due to the lytic activity of SNTX on the
      platelets.

PMID- 8533138
TI  - Structure-function studies of waglerin I, a lethal peptide from the venom of
      Wagler's pit viper, Trimeresurus wagleri.
AB  - Waglerins are 22-24 residue lethal peptides, found in the venom of Trimeresurus
      (Tropidolaemus) wagleri. The effects upon lethality and immunoreactivity
      resulting from structural modifications of these peptides were studied. A
      synthetic analogue with alanine residues in place of the two half-cystines of
      native peptide was nontoxic, suggesting that the single intramolecular disulfide
      bond in waglerins is critical for bioactivity. Substituting glutamic acid for
      aspartic acid at residue 5 slightly diminished lethality. Analogues containing
      asparagine instead of aspartic acid at residue 5 and/or a carboxamide- instead of
      a carboxy-terminus were lethal, demonstrating that neither a negative charge on
      residue 5 nor on the carboxy-terminus was required for bioactivity. A proteolytic
      fragment of waglerin I containing residues 6-22 was isolated and proved nontoxic.
      Therefore, one or more of the first five residues were necessary for bioactivity.
      Antiserum against waglerin I bound strongly to waglerins I, II, and SL-I, and to
      various analogues, proteolytic fragments, and chemically modified waglerin I.
      These findings suggest that the antibodies might be directed mainly against
      short, linear epitopes, implying an extended conformation for waglerin I.

PMID- 8533139
TI  - Bovine serum albumin does not completely block synaptosomal cholinergic
      activities of presynaptically acting snake venom phospholipase A2 enzymes.
AB  - Bovine serum albumin (BSA), which binds fatty acids, was used to test the
      contribution of free fatty acid to the presynaptic toxicity of phospholipase A2
      (PLA2) enzymes. The effects of BSA on inhibition of [14C]choline uptake and
      stimulation of [14C]acetylcholine (ACh) release in synaptosomes by PLA2 enzymes
      that do not have a predominant presynaptic action at the neuromuscular junction
      (PS-) were compared with those on the cholinergic actions of PLA2 enzymes that do
      have a predominant presynaptic action at the neuromuscular junction (PS+). The
      inhibition of choline uptake by the Naja naja atra PLA2, a PS- PLA2, was
      completely antagonized by BSA (0.5%); whereas that by beta-bungarotoxin, a PS+
      PLA2, was unaffected by BSA. The inhibition of choline uptake by two other PS+
      PLA2 toxins (scutoxin and pseudexin) was partially antagonized by BSA. The
      effects of the PLA2 enzymes were antagonized in the same manner by BSA whether on
      Na(+)-dependent or on Na(+)-independent choline uptake. Likewise, the stimulation
      of ACh release by two PS- PLA2 enzymes (from Naja naja atra and Naja naja
      kaouthia snake venoms) was completely blocked by BSA; whereas that by beta
      bungarotoxin was unaffected and that by scutoxin and pseudexin was only partially
      antagonized by BSA. The results suggest that the PS- PLA2 enzymes are completely
      dependent on fatty acid production for their cholinergic toxicity and that BSA
      can be used to investigate further the neurotoxic mechanisms of PS+ PLA2 enzymes
      in synaptosomes.

PMID- 8533140
TI  - Proteolytic specificity of two hemorrhagic factors, LHF-I and LHF-II, isolated
      from the venom of the bushmaster snake (Lachesis muta muta).
AB  - Two hemorrhagic metalloproteinases (LHF-I and LHF-II) were previously isolated
      from Lachesis muta muta (bushmaster snake) venom. The proteolytic activities of
      these hemorrhagic factors and of the crude venom were investigated using as
      substrate the oxidized B-chain of bovine insulin. LHF-II cleaves the Ala14-Leu15
      bond of insulin B-chain very rapidly and the Phe24-Phe25, His10-Leu11 and His5
      Leu6 more slowly, whereas LHF-I hydrolyzed only the Ala14-Leu15 bond. Both
      hemorrhagic factors cleaved the Leu-Leu bond in the fluorogenic peptide Abz-Pro
      Leu-Gly-Leu-Leu-Gly-Arg-EDDnp. When the insulin B-chain was incubated with crude
      venom previously treated with 2.5 mM PMSF, the Ala14-Leu15 bond was also rapidly
      cleaved. In addition, the hemorrhagic activity and the digestion of casein
      remained unaltered. Both hemorrhagic and proteolytic activities were inhibited
      when the crude venom was treated with EDTA, confirming that only
      metalloproteinases are responsible for these activities. The hydrolysis of
      insulin B-chain and the fluorogenic heptapeptide by these proteinases was found
      to be in inverse relationship to their hemorrhagic activities.

PMID- 8533141
TI  - The effects of a purified toxic extract of Prymnesium patelliferum on transport
      of ions through the plasma membrane of synaptosomes.
AB  - Extract of the ichthyotoxic marine alga Prymnesium patelliferum has been shown to
      have several different effects on the transport of neurotransmitters across nerve
      membranes. It inhibits the sodium dependent uptake of L-glutamate and GABA and
      enhances the calcium-dependent release of acetylcholine. We have therefore
      investigated the effects of a purified toxic extract of P. patelliferum on some
      membrane properties using rat brain synaptosomes. We found that under conditions
      where the algal extract inhibited the uptake of L-glutamate, it increased the
      intracellular concentrations of Na+ and Ca2+, stimulated efflux of K+ determined
      as 86Rb efflux, and depolarized the synaptosomal membrane. There was no effect on
      Na+/K(+)-ATPase or ouabain-insensitive ATPase activities. Further, there was no
      leakage of the cytosolic marker LDH, indicating that the various effects of the
      algal extract were not due to nonspecific leakage or lysis of the synaptosomes.
      The rise in the cytosolic concentration of free Ca2+ induced by the algal extract
      was dependent on extracellular Ca2+, and was inhibited by flunarizine (1-100
      microM) but not by the Ca2+ channel blockers omega-conotoxin GVIA (1 microM),
      diltiazem (100 microM), nifedipine (100 microM) or verapamil (100-500 microM).
      The increase in Na+ influx induced by the algal extract was insensitive to
      tetrodotoxin (3 microM) and procaine (100 microM), whereas both the Na+ influx
      and the membrane depolarization were inhibited by flunarizine (1-100 microM). The
      increase in K+ efflux was insensitive to flunarizine (5-100 microM). From these
      results it appears that the toxic extract of P. patelliferum increases the
      permeability of synaptosomes to Ca2+, Na+ and K+ and that these effects may be
      responsible for the plasma membrane depolarization and the disturbance of the
      neurotransmitter transport processes.

PMID- 8533142
TI  - Characterization of a thrombin-like enzyme, grambin, from the venom of
      Trimeresurus gramineus and its in vivo antithrombotic effect.
AB  - A thrombin-like enzyme, grambin, was purified to homogeneity by gel filtration,
      affinity and ion-exchange chromatography from the venom of Trimeresurus
      gramineus. Its mol. wt was estimated to be 45,400 by SDS-PAGE under reduced
      conditions. The mass of neutral sugars in grambin is estimated to be 20.7% of
      total mass. Grambin's NH2-terminal ten amino acid residues show a high homology
      to other venom thrombin-like enzymes. It clots human fibrinogen with a specific
      activity of 220-250 NIH thrombin-equivalent units/mg protein. It preferentially
      releases fibrinopeptide A accompanied by a slow release of trace amounts of
      fibrinopeptide B as monitored by HPLC following enzyme treatment of fibrinogen.
      EDTA, aprotinin, hirudin and heparin did not affect the fibrinogen-clotting
      activity of grambin in purified human fibrinogen solution. Diisopropyl
      fluorophosphate, phenylmethylsulfonyl fluoride and leupeptin inhibited the
      clotting activity of grambin whereas iodoacetamide did not affect its activity,
      indicating that grambin is a serine protease rather than a cysteine protease. In
      addition, it caused defibrinogenation and showed a marked antiplatelet effect
      when administered intravenously to mice. It also significantly prolonged the time
      lapse of platelet-rich thrombus formation in the irradiated mesenteric venules of
      fluorescein sodium-treated mice. Therefore, grambin may be used as a therapeutic
      agent not only in treatment of venous thrombosis but also in prevention of
      arterial thrombosis.

PMID- 8533143
TI  - Positive cooperativity among insecticidal scorpion neurotoxins.
AB  - The insecticidal activity of scorpion neurotoxic polypeptides increased 5-10-fold
      with no apparent increase in mammalian toxicity when a combination of two toxins
      was injected. Synergistic combinations could be predicted from binding studies
      and competitive displacement assays. Our results indicate that simultaneous
      expression in baculovirus or other transgenic organisms of the synergistic
      combinations of insecticidal toxins may result in more potent insect-selective
      biopesticides.

PMID- 8533144
TI  - Immunological studies on BaH1 and BaP1, two hemorrhagic metalloproteinases from
      the venom of the snake Bothrops asper.
AB  - No immunological cross-reactivity was observed between BaH1 and BaP1, two
      hemorrhagic metalloproteinases isolated from B. asper venom, by gel
      immunodiffusion, Western blotting and neutralization studies. Cross-reactivity
      was detected with antisera against these toxins in several crotaline and viperine
      snake venoms by ELISA, whereas no reactivity was observed with either antiserum
      against the venoms of Bothrops nummifer, Crotalus durissus terrificus, Vipera
      russelli and several elapid venoms. Antiserum against native BaH1 neutralized
      hemorrhagic activity of the venoms of B. asper, B. atrox, B. jararaca, Crotalus
      atrox, C. durissus durissus, Echis carinatus and Trimeresurus flavoviridis, being
      ineffective against the venoms of Agkistrodon bilineatus and Lachesis muta.

PMID- 8533145
TI  - Bibliography of toxinology.

PMID- 8533146
TI  - Out of the shadows and into the light: the emergence of DNA repair.

PMID- 8533147
TI  - Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3
      kinase.

PMID- 8533148
TI  - What's old is new: an alternative DNA excision repair pathway.

PMID- 8533149
TI  - Homologous recombination and the roles of double-strand breaks.
AB  - Double-strand breaks (DSBs) and single-strand gaps in damaged DNA are efficiently
      repaired by mechanisms associated with recombination. Recombination is a series
      of complex biochemical reactions, requiring at least 20 gene products, even in
      Escherichia coli. Genes homologous to bacterial and yeast recombination genes
      have been cloned in higher eukaryotes, suggesting there might be a common
      fundamental mechanism of recombination among a wide variety of species. In
      eukaryotes, protein-protein interactions play important roles in recombination:
      by interacting with a specific protein(s), the complex involved in repair of DSBs
      is modified to carry out specialized cellular functions, such as meiotic
      recombination and switching of mating types in yeast.

PMID- 8533150
TI  - The base excision repair pathway.
AB  - The base excision repair pathway has evolved to protect cells from the
      deleterious effects of endogenous DNA damage induced by hydrolysis, reactive
      oxygen species and other intracellular metabolites that modify DNA base
      structure. However, base excision repair is also important to resist lesions
      produced by ionizing radiation and strong alkylating agents, which are similar to
      those induced by endogenous factors.

PMID- 8533151
TI  - Mismatch repair: mechanisms and relationship to cancer susceptibility.
AB  - DNA mismatch-repair systems exist that repair mispaired bases formed during DNA
      replication, genetic recombination and as a result of damage to DNA. Some
      components of these systems are conserved in prokaryotes and eukaryotes. Genetic
      defects in mismatch-repair genes play an important role in common cancer
      susceptibility syndromes and sporadic cancers.

PMID- 8533152
TI  - Nucleotide excision repair and the link with transcription.
AB  - Nucleotide excision repair (NER) uses the products of about 30 genes to remove a
      damage-containing oligonucleotide from cellular DNA. The transcription factor
      TFIIH is an essential component of NER. In man, defects in NER can result in
      three distinct genetic disorders, whose features can be ascribed to abnormalities
      in DNA repair or transcription.

PMID- 8533153
TI  - Post-translational modification of poly(ADP-ribose) polymerase induced by DNA
      strand breaks.
AB  - There are one million molecules of poly(ADP-ribose) polymerase (PARP) in
      mammalian cell nuclei and the enzyme is found in most eukaryotes, with the
      notable exception of yeasts. In response to DNA damage caused by ionizing
      radiation or alkylating agents, PARP binds to strand interruptions in DNA and
      undergoes rapid automodification with synthesis of long branched polymers of
      highly negatively charged poly(ADP-ribose). DNA repair occurs after dissociation
      of modified PARP from DNA strand breaks. Biochemical data with enzyme-depleted
      extracts and studies of enzyme-deficient mice show that PARP does not participate
      directly in DNA repair. Possible roles for poly(ADP-ribose) synthesis are
      discussed.

PMID- 8533154
TI  - DNA double-strand break repair and V(D)J recombination: involvement of DNA-PK.
AB  - Two processes involving DNA double-strand breaks (DSBs) are the repair of DNA
      damage induced by ionizing radiation, and V(D)J recombination, the genomic
      rearrangement that creates antigen-receptor diversity in vertebrates. Recent
      evidence indicates that DNA-dependent protein kinase (DNA-PK), which is activated
      by DNA ends, is a central component of both the DNA DSB repair and V(D)J
      recombination machineries.

PMID- 8533155
TI  - SOS-regulated proteins in translesion DNA synthesis and mutagenesis.
AB  - Studies of Escherichia coli have revealed that most mutagenesis resulting from
      exposure to UV radiation and various chemicals (SOS mutagenesis) requires the
      operation of a specialized system involving the UmuD', UmuC, RecA and DNA
      polymerase III proteins, which allows translesion synthesis to occur on damaged
      DNA templates. The SOS mutagenesis system is induced by DNA damage and is subject
      to elaborate regulatory control involving both transcriptional derepression and
      post-translational activation and inhibition. The implications of the E. coli SOS
      mutagenesis system for mutagenesis in other organisms are discussed.

PMID- 8533156
TI  - DNA repair in three dimensions.

PMID- 8533157
TI  - Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles
      of p53 and ATM.
AB  - 'Checkpoint' controls arrest the cell cycle after DNA damage, allowing repair to
      take place before mutations can be perpetuated. In multicellular organisms, DNA
      damage can also induce apoptotic cell death, protecting the organism at the
      expense of the individual cell. How does a cell 'choose' between cycle arrest and
      death? Analysis of two human tumour suppressor proteins, p53 and the ATM (ataxia
      telangiectasia mutated) gene product, may provide some answers.

PMID- 8533158
TI  - The role of p53 in regulating genomic stability when DNA and RNA synthesis are
      inhibited.
AB  - In addition to its induction by DNA damage, p53 is induced by drugs that starve
      cells for DNA and RNA precursors, or by inhibitors of DNA or RNA polymerase. In
      normal cells, the induction of p53 by dNTP starvation serves a protective role,
      mediating rapid, reversible cell-cycle arrest without DNA damage. In most cell
      lines, this first line of defense is missing, so that starvation for dNTPs causes
      DNA to break, thus increasing the probability of genomic instability, chromosome
      deletions and gene amplification. The mechanism of how p53 is induced remains
      unclear.

PMID- 8533159
TI  - Cisplatin and DNA repair in cancer chemotherapy.
AB  - Cisplatin, a DNA-damaging agent, is one of the most widely used anticancer drugs.
      As with all members of this class of chemotherapeutic compounds, the clinical
      success of cisplatin is compromised if tumor cells become resistant by various
      mechanisms, including enhanced DNA repair. In addition to its role in resistance,
      DNA repair has been linked to the cytotoxic mechanism of cisplatin. DNA damaged
      by the drug has proved to be a valuable tool for exploring the details of the
      nucleotide excision repair pathway.

PMID- 8533160
TI  - A complex issue.

PMID- 8533161
TI  - The genetic basis of quantitative variation: numbers of sensory bristles of
      Drosophila melanogaster as a model system.
AB  - The numbers of sensory hairs of Drosophila melanogaster present an ideal model
      system to elucidate the genetic basis of morphological quantitative variation.
      Loci affecting bristle number can be identified and their properties studied by
      accumulating spontaneous mutations, by P element mutagenesis, by mapping factors
      causing divergence between selection lines and by the association of phenotype
      variation with molecular variation at candidate neurogenic loci. The consensus
      emerging from the application of all approaches is that much of the mutational
      and segregating variation affecting bristle number is attributable to alleles
      with large phenotype effects at a small number of candidate loci.

PMID- 8533162
TI  - Taking stock of complex trait genetics in mice.
AB  - The mapping of complex trait loci in mice has recently become very popular thanks
      to dense genetic maps, better approaches to linkage analysis and the continued
      value of the mouse as a key model organism for human disease. Nevertheless, the
      ultimate goal remains very difficult to identify genes that underlie complex
      traits and to understand their function at a molecular level. In assessing the
      prospects of current efforts, it helps to review the findings of earlier studies
      of complex traits and, despite all the technology, to be reminded of the inherent
      benefits and limitations at the source of genetic variation: the laboratory
      mouse. With the right perspective it should be possible for geneticists analysing
      complex traits to take full advantage of the resources that the genome project
      will provide.

PMID- 8533163
TI  - Mapping and manipulating quantitative traits in maize.
AB  - Maize has been used effectively as a model organism in the development and
      evaluation of molecular markers for the identification, mapping and manipulation
      of major genes affecting the expression of quantitative traits in plants.
      Although quantitative geneticists have recognized the possibility of major loci,
      the general dogma had emerged that quantitative traits were controlled by many
      loci, each with a small effect. This interpretation sent a quantitative traits
      because it would be essentially impossible to isolate a gene responsible for the
      trait. Recent results from numerous mapping studies have shown that quantitative
      traits are controlled by, at least some, factors with major effects, and have
      given credibility to the conclusion that major loci exist and that one might be
      able to study them. Positive results from marker-facilitated selection and
      introgression studies have further strengthened this conclusion.

PMID- 8533164
TI  - QTL mapping in rice.
AB  - In the past 10 years, interest in applying the tools of molecular genetics to the
      problem of increasing world rice production has resulted in the generation of two
      highly saturated, molecular linkage maps of rice, and the localization of
      numerous genes and quantitative trait loci (QTLs). Primary studies have
      identified QTLs associated with disease resistance, abiotic stress tolerance and
      yield potential of rice in a range of ecosystems. The ability to identify,
      manipulate and potentially clone individual genes involved in quantitatively
      inherited characters, combined with the demonstrated conservation of numerous
      linkage blocks among members of the grass family, emphasizes the contribution of
      map-based genetic analyses both to applied and to basic crop research.

PMID- 8533165
TI  - Livestock QTLs--bringing home the bacon?
AB  - Markers have been used for some time to study the genetic control of economically
      important traits in livestock. The early work was based on single loci and
      detected some significant effects, but results were often inconsistent across
      studies. Now that complete microsatellite-based maps of the major species are
      becoming available, more complete and rigorous scans of the genome are possible.
      The first of these have detected some surprisingly large effects, both within
      breeds and in breed crosses. As research workers digest these results and their
      implications for livestock breeding programmes and ponder further research,
      commercial breeding companies have already started applying the first fruits of
      marker research to breed a better animal.

PMID- 8533166
TI  - The HLA system and the analysis of multifactorial genetic disease.
AB  - The human leukocyte antigen (HLA) system comprises closely linked genes
      controlling highly polymorphic proteins involved in the presentation of peptides
      to the T-cell receptor. Specific alleles at HLA loci are associated with
      diseases, often those suspected to be of autoimmune aetiology. Many of these
      associations result from linkage disequilibrium between the HLA gene studied and
      other HLA genes or non-HLA genes close by. Owing to its high level of
      polymorphism and its candidate role in many diseases, HLA was the first system
      used in many techniques of genetic mapping, such as affected-sib-pair analysis
      and association (linkage disequilibrium) studies. Much remains unknown about the
      reasons why diseases are associated with HLA. Experience gained from HLA has,
      however, shown how other loci involved in complex traits can be identified by
      studying families with multiple affected cases or sib pairs, followed by linkage
      disequilibrium mapping and then analysis of candidate genes.

PMID- 8533167
TI  - Multifactorial inheritance in type 1 diabetes.
AB  - To date, twelve separate chromosome regions have been implicated in the
      development of human type 1 (insulin-dependent) diabetes mellitus. The major
      disease locus, IDDM1 in the major histocompatibility complex(MHC) on chromosome
      6p21, accounts for about 35% of the observed familial clustering and its
      contribution to disease susceptibility is likely to involve polymorphic residues
      of class II molecules in T-cell-mediated autoimmunity. IDDM2 is encoded by a
      minisatellite locus embedded in the 5' regulatory region of the insulin gene.
      Familial clustering of disease can be explained by the sharing of alleles of at
      least 10 loci. IDDM1 and IDDM2 interact epistatically. For a multifactorial
      disease, such as type 1 diabetes, important information concerning the pathways
      and mechanisms involved can be gained from examining such interactions between
      loci, using methods that simultaneously take account of the joint effects of the
      various underlying genetic components.

PMID- 8533168
TI  - Genetic susceptibility to Alzheimer disease.
AB  - Alzheimer disease (AD) is the leading cause of dementia in the elderly. Less than
      a decade ago, it was questioned as to whether or not genes were even involved in
      anything but rare early onset AD. Since that time, using a variety of genetic
      epidemiological and molecular biological techniques, four loci have been
      identified that play a role in the genetic susceptibility of AD. AD presents as a
      prototype of the power of genetic techniques in defining the etiology of a
      complex disease.

PMID- 8533169
TI  - Xenogenetics in multifactorial disease susceptibility.
AB  - Susceptibility to multifactorial disease includes both genetic and environmental
      components. These two aspects of susceptibility are interlinked through genetic
      control of an individual's response to the environment. As a first step in
      identifying disease susceptibility genes that influence the response of an
      individual to foreign compounds (xenobiotics), it is necessary to study disorders
      in which there is an identified environmental trigger. Establishing a DNA
      resource from individuals with known environmental exposure ('a xenogenetic
      register') for diseases with an established environmental aetiology is an
      essential step in beginning to understand how environmental factors contribute to
      the susceptibility to polygenic diseases. A complementary approach to
      identification of environmental factors is suggested using a comparison of
      genetically homogeneous subdivisions of individuals with polygenic diseases where
      there is no clue to the environmental trigger.

PMID- 8533170
TI  - Polygenic disease: methods for mapping complex disease traits.
AB  - Improved genotyping technology has made it feasible to use a genetic approach to
      map genes involved in the etiology of common human diseases. We discuss here
      recent developments in several different statistical approaches to linkage
      analysis of these traits, including affected-sib-pair methods, the affected
      pedigree-member method, regressive models and linkage-disequilibrium-based
      approaches. We discuss advantages and disadvantages of the various approaches, as
      well as factors influencing study design and the ability to detect loci.
      Statistical methodology in this area is advancing rapidly and will help enable
      the mapping and cloning of loci involved in susceptibility to common
      multifactorial diseases.

PMID- 8533172
TI  - XIII National Meeting of Experimental and Clinical Oncology. Verona, 15-18
      October 1995. Abstracts.

PMID- 8533171
TI  - Ethical concerns in the research and treatment of complex disease.
AB  - Research on and treatment of complex diseases raise familiar ethical issues
      concerning informed consent, privacy, confidentially, insurability, employability
      and social stigma. Consideration of the family as the unit of study, or point of
      medical intervention, presents some additional twists to these common ethical
      concerns. In addition, complex diseases present particular ethical challenges
      because different social and political incentives accompany placing emphasis on
      either the genetic or the environmental components of the diseases (e.g. in
      allocating research funds or ascribing responsibility for illness).

PMID- 8533173
TI  - Under buffer SFM observation of immunospecies adsorbed on a cyano grafted silicon
      substrate.
AB  - Scanning force microscopy (SFM) in contact mode and in liquid medium has been
      employed to study immunospecies layers adsorbed on a silicon wafer. The silicon
      wafer has been grafted with a cyanosilane monolayer in order to create a surface
      with strong adhesive properties which prevent proteins being swept by the scan of
      the SFM tip. The force curves reveal that the adhesive force has been increased
      by a factor six without roughness modification (< 1 nm). After the incubation of
      the surface in a monoclonal antibody (mouse anti-human alpha-fetoprotein IgG)
      solution, SFM surface images suggest an homogeneous layer composed by ellipsoidal
      objects (40-60 nm in diameter, 6-13 nm in height). The substrate was moreover
      incubated in an antigenic solution (human alpha-fetoprotein): SFM images reveal
      that proteins have been added onto the antibody layer.

PMID- 8533174
TI  - Reversed metal replicas of freeze-dried proteins to be visualized with the
      scanning tunneling microscope.
AB  - Scanning tunneling microscopy of metal-coated specimens has become a reliable
      technique that permits direct three-dimensional visualization of structural
      details at a level at which individual subunits in protein complexes or even
      single domains of proteins can be resolved. We describe in this paper a variation
      of the freeze-drying metal coating procedure that allows us to image with the STM
      the inner side of the metal replica, previously in contact with the protein
      molecules. We have tested this new approach with two different well characterized
      protein systems: freeze-dried two-dimensional crystals of bacteriophage phi 29
      connector and the vesicle form of two-dimensional crystals of cytochrome oxidase
      from beef heart mitochondria. The images obtained have very good contrast and
      provide direct topographic information of the crystal surface, complementing
      structural information obtained previously with transmission electron microscopy.
      The resolution limit is imposed by the size (2-3 nm diameter) and corrugation of
      the metal grains used to prepare the replica and by the randomness of the metal
      shadowing.

PMID- 8533175
TI  - The effect of minimal exercise on fitness in elderly women after hip surgery.
AB  - To determine the effect of minimal exercise on functional fitness following total
      hip replacement in elderly women, 20 women (13 exercisers, 7 controls) who had
      undergone unilateral or bilateral hip replacement surgery for primary
      osteoarthritis were studied. An exercise treadmill test with respiratory gas and
      blood lactate analyses, and a field test of walking speed on a measured course,
      were administered before and after a twice weekly exercise programme of three
      months' duration. Markers of cardiorespiratory fitness, including peak achieved
      oxygen uptake (VO2) and ventilatory and lactate thresholds were measured. Maximum
      self-selected walking speed was also measured over a flat course. Peak VO2
      increased in the exercise group when compared to baseline (P < 0.05) but did not
      differ from the control group. The exercise group significantly improved their
      walking speed by 10.1% compared with non-exercising controls (1.41 vs 1.20 m/sec,
      P < 0.05), and increased VO2 at lactate threshold. The improvements occurred
      despite the twice weekly exercise sessions being below the recommended frequency
      of exercise for improving cardiorespiratory fitness. Minimal exercise in elderly
      women after hip surgery can substantially improve submaximal exercise capacity,
      as well as walking speed.

PMID- 8533176
TI  - Laser lithotripsy for ureteric calculi: results in 250 patients.
AB  - Two hundred and fifty patients with 290 stones presenting to the Department of
      Urology were treated with the Candela MDL 2000 Laser Lithotripter. Overall stone
      clearance rate was 95%. The more proximal the calculus the lower the success
      rate. Ninety eight percent of stones in the lower ureter, 95% of mid ureteric and
      91% of upper ureteric stones were cleared. The major complication was perforation
      which occurred in 6% of cases. This procedure is a safe and effective treatment
      for ureteric calculi and is associated with a low complication rate and a high
      clearance rate. Laser lithotripsy is the optimum ureteroscopic method of treating
      ureteric calculi and is complimentary to extra corporeal shock wave lithotripsy.

PMID- 8533177
TI  - Diagnostic regimes for urinary tract infection--are research results applied to
      practice?
AB  - A clinical audit of ward practice for diagnosing and treating urinary tract
      infection was carried out to assess the impact on clinical practice four years
      after publication of a working protocol. Data were collected from all medical,
      surgical, gynaecology and geriatric wards in 25 hospitals in Northern Ireland.
      All wards made use of urinary dipsticks for ward testing, as recommended by the
      protocol. However many negative samples were still forwarded for laboratory
      analysis. The potential financial savings which would result from effective ward
      screening were not being realised and the publication appeared to have minimal
      impact on clinical practice. Advice on an improved diagnostic protocol for
      urinary tract infection may not have been disseminated to the nursing staff whose
      role was pivotal in the screening process.

PMID- 8533178
TI  - Comparison of nursing home residents admitted from home or hospital.
AB  - A growing elderly population coupled with a reduction in hospital long term care
      has led to an increase in the independent nursing home sector. This is an
      expensive resource. Proper placement is therefore essential to ensure its
      efficient use. Prior to the introduction of care management there was no standard
      assessment procedure for admission to nursing home care from different sources. A
      nursing home population (n = 624) in North and West Belfast was studied and
      mental scores, levels of disability, and the source of admission to the nursing
      home recorded. Residents admitted from geriatric medical units (n = 132) were
      compared with those from general medical and surgical wards (n = 168) and those
      from home (n = 243). Residents who were admitted from a geriatric unit were the
      most disabled, those admitted from home were the least and those from general
      wards had intermediate levels of disability (p < 0.005). This is likely to be the
      result of different assessment procedures for prospective nursing home residents.
      With the introduction of care management, it is hoped that standardised
      assessment will follow. The roles of different medical specialists in this
      process is not yet clear. Further study is needed to assess the appropriateness
      of placement in nursing homes under care management.

PMID- 8533179
TI  - The epidemiology of major trauma in Northern Ireland.
AB  - In a one year population based study of major trauma (Injury Severity Score
      greater than 15) reaching hospitals in Northern Ireland in 1990/91 the incidence
      was 23.2 per 100,000 of the population or 20.5 per 100,000 excluding terrorist
      activities. The expected number of patients with major trauma for the province,
      (population 1.54 million) is 359 patients per annum. Road accidents and falls
      accounted for 71% of all trauma. Ninetynine patients per annum are expected to
      require immediate surgery, a laparotomy in 59 instances and neurosurgical
      procedures in 26. These data facilitate resource allocation and help predict the
      effects of future changes in the trauma system.

PMID- 8533180
TI  - A critical evaluation of the use of the Schiller test in selecting blocks from
      the uterine cervix in suspected intraepithelial neoplasia.
AB  - The value of dipping cervical cone biopsy specimens in iodine (the Schiller test)
      as a method of deciding which areas should be selected for histological
      examination was assessed. Schiller positive and negative areas were recorded in
      macroscopic specimen images from fifty specimens of cervix. The results were
      compared with the histological presence or absence of cervical intraepithelial
      neoplasia (CIN) or invasive malignancy. In 84% of cases the test was a reliable
      means of predicting the presence or absence of squamous CIN; in two cases it was
      positive in association with endocervical adenocarcinoma in situ. A false
      positive and false negative Schiller's test was present in three cases (6%) each.
      Had this method been adopted as the sole means of selecting blocks for
      histological examination the areas of CIN would have been missed in 6% of cases.
      Therefore it is not a sound alternative to the submission of all tissue for
      histological examination.

PMID- 8533181
TI  - An audit of therapeutic drug monitoring of anticonvulsants.
AB  - An audit of therapeutic drug monitoring (TDM) of anticonvulsants was performed to
      assess both its use and misuse in the management of patients with epilepsy. Over
      a four week period all samples received for phenytoin, carbamazepine, sodium
      valproate and phenobarbitone assays were included in the audit. The aims were to
      establish the source of the specimens, the reasons for the requests and to
      ascertain what action, if any, would be taken when the result of the assay was
      provided. A total of 163 separate assays were performed over the four week period
      (43 phenytoin, 74 carbamazepine, 41 valproate, 5 phenobarbitone). Only 18.7% of
      all requests originated from the adult neurology department. The vast majority of
      tests had been ordered by junior medical staff (only 10% by consultants) and
      approximately 50% were 'routine' with no satisfactory clinical reason for the
      request offered. There was a tendency to manipulate prescribed doses on the basis
      of drug levels alone without taking the clinical picture into consideration.
      These results demonstrate a general ignorance, especially amongst junior medical
      staff, of the value of TDM of anticonvulsants, and reinforce the need for both an
      educative and interpretive service to be provided by the Chemical Pathology
      Department.

PMID- 8533183
TI  - The visual arts in Northern Ireland hospitals.
AB  - Since 1989 there has been a burgeoning of the visual arts in Northern Ireland
      hospitals. This paper compares the three organisational models for hospital arts
      currently operating within the Province and in an overview discusses ways to
      coordinate working practice for future development of the visual arts in local
      hospitals.

PMID- 8533182
TI  - Alcohol intake in patients admitted acutely to a general medical unit.
AB  - The role of alcohol in causing acute medical admissions is recognised but not
      well quantified. Using a questionnaire we have studied prospectively alcohol
      intake in patients aged 18-60 years admitted to a medical unit and have analysed
      the contribution of alcohol to their admission. One hundred and six patients (61
      male: 45 female) who fulfilled our preset age criteria were studied. Alcohol
      intake (mean +/- SEM) was 9 +/- 1 and 12 +/- 1 units on average and heavy
      drinking days respectively, and 38 +/- 6 units during their last drinking week.
      Gamma glutamyl transferase (GGT) was > 60 U/l (upper limit of normal) in 29 (n =
      92). Eighteen (30%) men had drunk > 50 units and seven (16%) women had taken > 35
      units in their last drinking week. In 25 (41%) men and 11 (24%) women alcohol
      intake was felt to contribute to their admission. In this subgroup, intake was 15
      +/- 2 and 20 +/- 1 units on average and heavy drinking days respectively, and 87
      +/- 13 units in the last drinking week. GGT was available in 29 and was abnormal
      in 18. Admission diagnoses were drug overdose (n = 16), alcohol withdrawal
      symptoms (n = 7), liver disease (n = 6), haematemesis (n = 14) and others (n =
      3). Fifteen (42%) felt they had a definite alcohol problem. The use and abuse of
      alcohol contributes significantly to the general medical workload in the age
      group studied.

PMID- 8533184
TI  - Intensive care management of the HELLP syndrome.

PMID- 8533185
TI  - Iatrogenic acute angle closure glaucoma masked by general anaesthesia and
      intensive care.

PMID- 8533186
TI  - Metastatic biphasic pulmonary adenocarcinoma mimicking malignant gastrointestinal
      stromal tumour.

PMID- 8533187
TI  - Hepatic abscess formation following embolisation of a carcinoid metastasis.

PMID- 8533188
TI  - Primary systemic amyloidosis and the gastrointestinal tract.

PMID- 8533189
TI  - Dietary deficiency of iron--an extreme example.

PMID- 8533190
TI  - Sequential changes in the prostatic fluid level of latamoxef in patients with
      acute bacterial prostatitis.
AB  - The sequential expressed prostatic secretion (EPS) levels of latamoxef (LMOX)
      were measured in 14 patients with acute bacterial prostatitis to evaluate the
      diffusion of this antibiotic from the plasma into the prostatic fluid. All
      patients received 2 g of LMOX on the 1st, 4th, and 7th days of hospitalization.
      The mean LMOX level in EPS and the EPS/serum ratio were 16.4 micrograms/ml and
      0.24 on the 1st day, 5.5 micrograms/ml and 0.08 on the 4th day, and 3.5
      micrograms/ml and 0.04 on the 7th day, respectively. The mean value of prostatic
      fluid was 7.7, 7.8, and 7.8, respectively. Thus, both the EPS level of LMOX and
      the EPS/serum ratio decreased along with the recovery from acute bacterial
      prostatitis and did not correlate with the pH gradient between prostatic fluid
      and plasma.

PMID- 8533191
TI  - Polyarteritis nodosa presenting as perirenal hemorrhage.
AB  - Though renal involvement with microaneurysm formation is common in polyarteritis
      nodosa (PAN), spontaneous perirenal hematoma (SPH) is rare. We report a patient
      in whom SPH was the presenting manifestation of PAN. SPH is a potential life
      threatening complication of PAN and its early recognition is emphasized.

PMID- 8533192
TI  - Renal pelvis rupture after blunt abdominal trauma.
AB  - A 45-year-old male patient presented with rupture of the left renal pelvis after
      blunt abdominal trauma. The patient had preexisting bilateral megaureters with
      secondary obstruction of the pyeloureteral junction. The underlying disease was a
      persisting type III posterior urethral valve. Diagnosis of renal pelvis rupture
      and the underlying malformation was achieved sonographically and by abdominal CT
      scan. The left kidney was exposed at the time of admission and a pyeloplasty
      according to Anderson-Hynes was carried out. Secondarily the urethral valve was
      resected.

PMID- 8533193
TI  - Retroperitoneal fibrosis: evaluation by ultrasonography and color Doppler
      imaging.
AB  - Delay in diagnosis is common in retroperitoneal fibrosis because of the non
      specific clinical presentation. Ultrasonography combined with color Doppler
      imaging is a rapid and practical method in the early diagnosis and during follow
      up. We describe 3 cases with retroperitoneal fibrosis, emphasizing the
      ultrasonographic and color Doppler features of the disease.

PMID- 8533194
TI  - Is heterotopic bone formation, occurring near a cut ureter, a sign of
      osteoinductive potency of human urothelium?
AB  - A bone formation in the ileo-lumbalis muscle following urine leakage from the
      injured ureter is reported. The role of osteoinductive potential of urothelium is
      discussed and negated.

PMID- 8533195
TI  - Squamous cell carcinoma of perineal urethrostomy.
AB  - Urethral malignancies are rare while only few cases of urethral carcinoma
      following urethroplasty have been reported in the literature. We present a case
      of squamous cell carcinoma at perineal urethrostomy.

PMID- 8533196
TI  - Down's syndrome associated with intracranial germinoma and testicular embryonal
      carcinoma.
AB  - In patients with Down's syndrome, the frequency of leukemia is significantly
      greater than normally would be expected. However, cancers other than leukemia
      have been reported to occur rarely. We present a case of Down's syndrome
      associated with intracranial germinoma and testicular embryonal carcinoma.
      Currently, no case of double primary carcinomas in Down's syndrome has been
      reported to the authors' knowledge.

PMID- 8533197
TI  - Infrequent involvement of mutations on neurofibromatosis type 1, H-ras, K-ras and
      N-ras in urothelial tumors.
AB  - The neurofibromatosis type 1 (NF1) gene is considered a tumor-suppressor gene
      whose product acts upstream of ras. The ras gene is an oncogene very commonly
      detected in human cancers and consists of three families, H-ras, K-ras and N-ras.
      These genes are converted to active oncogenes by point mutations in codon 12, 13,
      or 61. Examination was made of the mutations of these genes in 39 urothelial
      malignant tumors (31 bladder cancer, 6 renal pelvic tumor, and 2 ureter tumors)
      using polymerase chain reaction single-stranded conformation polymorphism and
      direct sequencing methods. Three of 39 (7.7%) cases showed mobility shifts in the
      ras family gene but no point mutations in NF1 and N-ras genes could be detected.
      Mutations were found in 1 case in H-ras at codon 13 (GGT-GTT/GGT) and K-ras at
      codon 12 in 2 cases (GGT-GCT/GGT, GGT-GTT/GGT). All 3 cases had progressed far
      beyond grade 2 and stage pT2. It follows from the above that NF1 and ras gene
      mutations are infrequent in the pathogenesis of urothelial tumors.

PMID- 8533198
TI  - Dual-parameter immunoflow cytometry--a new technique in the noninvasive diagnosis
      of bladder cancer.
AB  - The introduction of monoclonal antibodies into the diagnosis of transitional cell
      carcinoma (TCC) has been a further step toward the use of biological parameters
      to support conventional cytological diagnosis of this tumor entity. Several
      investigators have demonstrated the high sensitivity and good specificity of
      immunocytology. Nevertheless this technique is hampered by the inconvenient and
      time-consuming microscopic analysis. The purpose of this study was to combine the
      advantages of immunocytology with the capabilities of an automated flow
      cytometric system. Since all monoclonal antibodies (mAbs) currently used for
      immunocytology cross-react with granulocytes a preselection of urothelial cells
      becomes necessary for immuno-flow cytometry (immuno-FCM). Based on earlier
      analyses mAb Due AUT 2, reactive against urothelium and not against granulocytes,
      was chosen to preselect for urothelial cells. mAb Due ABC 3 was used to
      discriminate between normal and malignant urothelial cells. Initial experiments
      including 10 barbotage specimens from patients with histologically proven TCC and
      concomitant urinary tract infection yielded a high sensitivity (90%) of immuno
      FCM. In 10 control patients with malignancies other than bladder TCC and benign
      diseases ABC 3 expression was not increased. Flow-cytometric examination of
      irrigation specimens from 10 patients with a history of bladder cancer but
      without cystoscopic and cytologic evidence of tumor recurrence showed abnormal
      results in 6 patients. Rebiopsy and/or cystectomy confirmed tumor recurrence in 5
      of these patients and in 1 patient with negative immuno-FCM. Ongoing prospective
      trials will further define the clinical impact of this approach in the diagnosis
      and follow-up of patients with bladder cancer.

PMID- 8533199
TI  - Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper
      urinary tract.
AB  - Cisplatin-based multiple-drug chemotherapy is currently considered the most
      effective treatment for advanced and metastatic urothelial cancers. We treated 15
      patients with locally advanced urothelial cancers of the upper urinary tract
      using the cisplatin-based multiple-drug regimen in a neoadjuvant setting. The
      regimens administered were: M-VAC (methotrexate, vinblastine, doxorubicin and
      cisplatin); MEC (methotrexate, etoposide and cisplatin), or M-VEC (methotrexate,
      vinblastine, epirubicin and cisplatin). Total nephroureterectomy was performed in
      all patients and response was evaluated pathologically Of 15 patients 2 (13%)
      achieved a pathological complete response, 6 (40%) a pathological partial
      response, for an overall response rate of 53% (95% confidence limits 29-77%). The
      median durations of response were 54 months for patients with a pathological
      complete response and 15.5 months for patients with a pathological partial
      response. One of six patients with a pathological partial response and 4 of 7
      with no remission died of cancer. While a positive relationship between the
      pathological response and prognosis was observed, adequate follow-up is needed to
      assess the ability of neoadjuvant chemotherapy to improve the prognosis of
      patients with locally advanced urothelial cancer of the upper urinary tract.

PMID- 8533200
TI  - Laparoscopic pelvic lymphadenectomy in prostatic cancer: an analysis of seventy
      consecutive cases.
AB  - From July 1992 to April 1994, 70 patients with prostatic cancer underwent
      laparoscopic pelvic lymph-node dissection (LPLD) before retropubic radical
      prostatectomy or afterloading therapy in our clinic. After an initial learning
      phase, the accuracy of LPLD was excellent, with only 3.0% residual nodes and no
      false-negative results due to LPLD. The rate of severe complications was 5.7%
      (4/70). No transfusions were required due to LPLD. If patients with positive
      nodes (D1) were excluded from local therapy, the benefits of LPLD were estimated
      as 12 patients with positive nodes avoiding open surgery (17.1%); 15 patients
      undergoing afterloading therapy and avoiding open surgery (21.4%); 1 patient with
      high preoperative prostate-specific antigen having a chance of surgical cure
      (1.4%) - a total of 28 of 70 patients (40.0%). We conclude that, depending on the
      therapeutic concept applied, LPLD is beneficial for patients with prostatic
      cancer, it opens the door for other curative procedures like after-loading
      therapy, and reappraisal of perineal prostatectomy.

PMID- 8533201
TI  - Serial renal transplant surgery: technical reflections concerning third
      transplants.
AB  - From 1972 to 1993, we carried out 803 consecutive renal transplants including 8
      third transplants. Exclusively cadaveric, these third renal transplants were
      implanted by intraperitoneal approach in right iliac position, without previous
      homolateral transplantectomy in 5 cases. The arterial anastomoses were common (7)
      or external iliac and hypogastric (1), and the venous anastomoses external (1)
      and common iliac (3), or inferior vena cava (4). Restoration of urinary
      continuity was by ureteronecystostomy (Politano-Leadbetter = 4, Gregoir-Lich = 3)
      or ureteroureteric anastomosis (1). The level of HLA compatibility varied from 2
      to 5 identities (mean 3.1) and 4 of the 7 patients explored were hyperimmunized
      with lymphocytotoxic antibody levels > or = 80%. With the exception of the first
      of these third transplants, the immunosuppressive protocol associated
      azathioprine, prednisolone, antilymphocytic serum and cyclosporin. Postoperative
      sequels were marked by 3 vascular rejections and 1 death from hyperkalemia.
      Moreover, 1 urinary fistula on ureteroureteric anastomosis settled after
      percutaneous nephrostomy and placing of an uteric stent endoprosthesis. With a
      postoperative follow-up of 8-32 months (mean 24), 5 of the transplanted patients
      (62.5%) have a functional renal transplant with a serum creatinine from 120 to
      180 microM/l (mean 140). This brief series, whose failures are exclusively
      immunological, reveals the remarkable technical reliability for these third renal
      transplants in right iliac implantation, by median transabdominal approach and
      above a former transplant site.

PMID- 8533202
TI  - Idiopathic calcium oxalate urinary lithiasis: usefulness of Parks' and Tiselius'
      indices in the evaluation of the risk of stone formation.
AB  - Different indices of the risk of urinary calcium oxalate crystallization were
      compared to determine their usefulness in detecting the stone-formers
      particularly prone to recurrence. Urine volume and calcium, oxalate, citrate,
      magnesium or creatinine were determined in 55 patients presenting with an
      idiopathic calcium oxalate urolithiasis, as well as in 50 control subjects. On 24
      hour urine samples, these elements allowed for the calculation and comparison of
      different indices of lithogenous risk as proposed by Parks and Tiselius. Both
      Parks' indices and the urinary citrate-calcium ratio varied significantly between
      the two groups, but conversely Tiselius' indices were statistically comparable.
      The three Tiselius' indices taking the 24-hour urine volume into account were
      also strongly correlated. Parks' index and the urinary citrate-calcium ratio are
      highly discriminating and potentially relevant to select the stone-formers with a
      high risk of relapse. Tiselius' indices basically reflect urinary calcium oxalate
      saturation, and can only be used clinically to control the treatment interfering
      with this. In this respect, the formula based simply on urine volume, calcium and
      oxalate over 24 h (Ca0.71.Ox.V-1.2) appears to be sufficient.

PMID- 8533203
TI  - Determination of urinary calcium oxalate crystallization mechanisms and kinetics
      using flow cytometry.
AB  - This paper describes the application of flow cytometry to the determination of
      calcium oxalate crystallization kinetics and mechanisms in real urine. The
      technique has the unique advantage of simultaneously providing quantitative
      particle number-size distributions and qualitative data concerning particle
      structure and morphology. Twenty-four-hour urines from 10 healthy male subjects
      were treated with sodium oxalate and the ensuing crystallization of calcium
      oxalate was monitored by flow cytometry. In 7 specimens crystallization was
      accompanied by increasing size and by a fundamental change in particle
      morphology. This suggests that nucleation and aggregation occurred in these
      specimens. In the remaining 3 samples, increasing particle numbers occurred
      without any changes in size or morphology, indicating that nucleation was the
      sole mechanism in these specimens. These results demonstrate that flow cytometry
      is able to differentiate between nucleation, growth and aggregation mechanisms
      thereby making it an extremely useful analytical tool for stone researchers.

PMID- 8533204
TI  - Effect of tumor necrosis factor-alpha and interferon-gamma on the growth of human
      prostate cancer cell lines.
AB  - Human recombinant tumor necrosis factor-alpha (rTNF-alpha, 10(-12)-10(-8) M)
      inhibited the proliferation of androgen-dependent LNCaP cells by 32-56%. In
      contrast, proliferation of androgen-independent PC-3 and JCA-1 cells was only
      slightly inhibited, or not inhibited at all, respectively. Human recombinant
      interferon-gamma (rIFN-gamma, 500 U/ml) decreased proliferation of PC-3 and JCA-1
      cells by 35% and 53%, respectively, but had no effect on LNCaP cells.
      Interestingly, the combination of rIFN-gamma and TNF-alpha had greater
      antiproliferative effects on JCA-1 cells than treatment with either cytokine
      alone. However, the antiproliferative effects of this combination were similar to
      those observed for PC-3 or LNCaP cells treated with rIFN-gamma or TNF-alpha
      alone, respectively. These data suggest that some forms of androgen-independent
      prostate cancer may benefit from a combination therapy of IFN-gamma and TNF
      alpha, while the use of IFN-gamma alone may be more efficacious in others.

PMID- 8533205
TI  - Prognostic factors in patients with pathological stage I non-seminomatous
      testicular germ cell tumors and tumor recurrence during follow-up.
AB  - Clinical staging in patients with stage I non-seminomatous germ cell tumors
      (NSGCTs) of the testis fails in 30% to correctly assess pathological stage since
      microscopic and small-volume retroperitoneal disease is not detectable on
      computed tomography of the abdomen. Patients staged by retroperitoneal lymph node
      dissection as pathological stage I incur a distant (chest or serological) tumor
      relapse rate of 7-15% during follow-up. Recently, we reported on new risk factors
      as predictors of pathological stage by flow cytometric DNA analysis in clinical
      stage I patients. These same methods were applied to a group of 14 pathological
      stage I patients who subsequently had either chest or serological recurrence. The
      findings in this group of patients were compared with those in a group of 47
      pathological stage I patients who did not experience recurrence. In pathological
      stage I NSGCT patients with distant (chest or serological) tumor relapse, we
      found by histological evaluation and DNA analysis of the original orchiectomy
      specimen proliferative tumor activity to be significantly predictive of relapse.
      Much as proliferative activity of the primary tumor is predictive of
      retroperitoneal metastasis, it may be a predictor of recurrence in pathological
      stage I patients.

PMID- 8533206
TI  - Measurement of diurnal variations in urinary cystine saturation.
AB  - In an attempt to improve the diagnostic value of urine analysis in patients with
      homozygous cystinuria, we studied the diurnal variation in urine composition. A
      simplified estimate of the ion-activity product of cystine was used to increase
      the probability of identifying patients with a particular risk of stone
      formation. Eight 6-h urine samples were collected during two 24-h periods. The
      highest urinary excretion of cystine was recorded between 1200 and 1800 hours and
      the lowest between 0000 and 0600 hours, whereas the urinary cystine concentration
      was highest between 0000 and 0006 hours and lowest between 1200 and 1800 hours.
      The approximate ion-activity product of cystine had a maximal level between 0000
      and 0600 hours but a minimal level between 0600 and 1200 hours. The differences
      between different periods were numerically more pronounced in terms of the ion
      activity product of cystine than in terms of concentration. The peak
      concentrations of cystine in 6-h samples were about 90% higher than the
      corresponding concentrations in 24-h urine samples. It is concluded that the
      analysis of cystine in 6-h urine samples reveals transient episodes of cystine
      supersaturation that otherwise will remain undetected. Further studies are,
      however, needed to establish its usefulness in clinical practice.

PMID- 8533207
TI  - Scanning electron microscopy of the tunica albuginea of the corpora cavernosa in
      normal and impotent subjects.
AB  - The tunica albuginea (TA) of the penis is thought to play a major role in the
      erection mechanism. It functions by compressing the subalbugineae venulae, which
      promotes the slower venous flow during erection, and provides a fibrous frame to
      give an inextensible support for the vessels and nerves. It acts as the
      inextensible enclosing structure which contains the erectile tissue and gives the
      erect penis its shape. The functions of the TA result from its structure,
      consisting for the most part of collagenic and elastic fibers. This study
      investigated, with the aid of scanning electron microscopy (SEM), the
      microarchitecture of the TA and the spatial relation of its fibers in ten
      impotent patients and in six control subjects with normal erectile function. The
      arrangement of elastic fibers in the TA seems to account for their function,
      which is to prevent the overstretching of collagenic fibers during maximum
      intracavernous pressure. In impotent patients, a reduction in the elastic fibers
      in the TA appears to produce disorders in the arrangement of the collagenic
      fibers. These alterations in the architecture of the TA in impotent patients can
      give rise top erection disorders.

PMID- 8533208
TI  - Detection of aberrations in androgen receptor gene by analysis of single-stranded
      conformation polymorphisms in polymerase chain reaction products.
AB  - Analysis of single-stranded conformation polymorphisms in polymerase chain
      reaction (PCR) products (PCR-SSCP) is a sensitive method for detecting point
      mutations in genomic DNA. To investigate its utility in examining the androgen
      receptor gene, we analyzed data on a patient with the testicular feminization
      syndrome (TFS) with a known point mutation in exon C. We detected mobility shifts
      of fragments of the corresponding region. Since examination of the subject's
      brother (legally sister), who also has TFS, revealed an identical shift pattern,
      we sequenced the exon C of the sibling and detected a mutation identical to that
      in the former. We conclude that PCR-SSCP is available for screening mutations of
      the androgen receptor gene.

PMID- 8533209
TI  - Simultaneous measurements of calcium oxalate crystal nucleation and aggregation:
      impact of various modifiers.
AB  - Rates of nucleation and aggregation of calcium oxalate crystals were derived from
      20-min time course measurements of OD620 after mixing solutions containing CaCl2
      and K2C2O4 at 37 degrees C, pH 5.7, ionic strength (IS) 0.21, with constant
      stirring (500 rpm); final assay concentrations were 4.25 mM calcium and 0.5 mM
      oxalate, respectively. The maximum increase of OD620 with time, termed SN, mainly
      reflects maximum rate of formation of new particles and thus crystal nucleation.
      After equilibrium has been reached, OD620 progressively decreases despite ionized
      calcium staying constant and no new particles being formed, due to crystal
      aggregation. Rate of aggregation, SA, is derived from the maximum decrease in
      OD620 with time. SN and SA are not independent, as indicated by a positive
      correlation (r = 0.844, P = 0.0001). Among the modifiers studied, citrate at 0.5
      2.5 mM lowered both SN and SA in a concentration-dependent manner (P < 0.01 for
      all comparisons vs control). Chondroitin-6-sulfate at 6.25-25 mg/l moderately
      lowered SN, whereas it strongly inhibited aggregation (P < 0.01 vs control). At
      6.8-20.4 mg/l, albumin did not affect nucleation, whereas it inhibited
      aggregation in a concentration-dependent manner (P < 0.005 vs control for all
      comparisons).

PMID- 8533211
TI  - 1st World Congress on Urological Research. Rotterdam, The Netherlands, September
      1-3, 1995. Abstracts.

PMID- 8533210
TI  - Evaluation of four animal models of intrarenal calcium deposition and assessment
      of the influence of dietary supplementation with essential fatty acids on
      calcification.
AB  - Firstly, to determine a satisfactory animal model for induction of intrarenal
      calcification, a study of four previously described animal models of intrarenal
      calcification was carried out which showed that intraperitoneal injection of 10%
      calcium gluconate into female Sprague-Dawley rats was most effective. We then
      investigated the hypothesis that dietary supplementation with essential fatty
      acids could reduce the intrarenal calcification developing as a result of
      intraperitoneal calcium injection. Using a combination of fish oil and evening
      primrose oil, we demonstrated a significant difference in renal parenchymal
      calcification, which was 940 +/- 240 micrograms Ca/g dry weight renal parenchyma
      in unsupplemented animals and 320-370 +/- 55-65 micrograms Ca/g dry weight renal
      parenchyma in supplemented animals (means +/- SEM, P < 0.005). It was also
      demonstrated that there was synergism between eicosapentaenoic acid (EPA) and
      gamma-linolenic acid (GLA): dietary supplementation with a combined oil
      preparation containing 27 mg/ml EPA and 67 mg/ml GLA mixed as 2% with food was as
      effective as oils containing either 400 mg/ml EPA or 80 mg/ml GLA mixed as 4% of
      food.

PMID- 8533212
TI  - EC bans use of dimetridazole in food animals.

PMID- 8533213
TI  - CIWF calls for ban on genetic engineering of farm animals.

PMID- 8533214
TI  - Virulence and genotype of a bovine herpesvirus 1 isolate from semen of a
      subclinically infected bull.
AB  - A bovine herpesvirus 1 (BHV-1) isolate from the semen of a subclinically infected
      bull was administered to cattle by various routes to assess its virulence. Cattle
      that were artificially inseminated or inoculated intrapreputially did not develop
      clinical signs, but did transmit the virus to contact cattle. However, the
      isolate induced severe signs of rhinotracheitis and vulvovaginitis in cattle that
      were inoculated by the intravaginal, intranasal or intravenous routes, but did
      not infect the fetus. The isolate was therefore not of low virulence. Analysis
      with DNA restriction enzymes could not assign the isolate to either the BHV-1.1
      or BHV-1.2 genotype.

PMID- 8533215
TI  - Porcine membranoproliferative glomerulonephritis type II: an autosomal recessive
      deficiency of factor H.
AB  - Hypocomplementaemic hereditary membranoproliferative glomerulonephritis (MPGN)
      type II is a common cause of the early loss of piglets in the Norwegian Yorkshire
      breed. The disease is associated with extensive complement activation due to a
      deficiency of factor H, a plasma protein which regulates complement. To
      investigate its mode of inheritance, 33 litters were bred from healthy animals
      associated with the disease, and a total of 385 recorded offspring were produced.
      The examination of renal tissue from the hypocomplementaemic piglets consistently
      revealed diagnostic signs of MPGN type II, including thickening of the glomerular
      capillary wall and proliferation of mesangial cells, dense intramembranous
      deposits, and massive glomerular deposits of complement component C3 and the
      terminal complement complex. No such glomerular lesions were detected in 20
      normocomplementaemic littermates. The 88 affected piglets were present in 27
      litters containing a total of 317 piglets, and there were approximately equal
      numbers of each sex. Retrospective immunoblot analysis and enzyme immunoassay of
      plasma samples from the MPGN-affected piglets and their healthy littermates
      revealed that the affected piglets were deficient in factor H, whereas the
      healthy piglets were not. It is concluded that porcine factor H deficiency is
      inherited as a simple autosomal recessive trait with complete penetrance, and
      consistently results in hypocomplementaemia and lethal membranoproliferative
      glomerulonephritis type II.

PMID- 8533216
TI  - Angular limb deformity in a calf treated by periosteotomy and wedge osteotomy.
AB  - A carpus valgus deformity was diagnosed in a five-week-old Brown Swiss calf. The
      45 degrees deformity was caused by the malaligned healing of a fracture of the
      left metacarpus after birth trauma. The deviation improved to 25 degrees after
      being treated with a semicircular lateral periosteotomy above the distal physis
      of the radius. A complete correction was made by means of a wedge osteotomy five
      months after the first treatment. A 20 degrees wedge of bone was removed. The
      metacarpus was stabilised with a seven-hole dynamic compression plate which was
      removed 12 weeks later. Thirty months later the calf was sold as a pregnant
      heifer at an auction of breeding cattle.

PMID- 8533217
TI  - Metastatic pilomatrixoma associated with neurological signs in a dog.

PMID- 8533219
TI  - Percutaneous absorption of metal ions.

PMID- 8533218
TI  - Veterinary manpower: a new approach to practice.

PMID- 8533220
TI  - Treatment of canine visceral leishmaniasis with allopurinol.

PMID- 8533221
TI  - Evaluation of doramectin in a programme for season-long control of parasitic
      gastroenteritis in calves.
AB  - Doramectin was used in a strategic programme for the prevention of parasitic
      gastroenteritis in first season grazing calves. Three groups of nine calves were
      used: group 1 was left untreated, group 2 was treated with doramectin at 0.2
      mg/kg at turnout and again eight weeks later, and group 3 was treated with 0.2
      mg/kg ivermectin at three, eight and 13 weeks after turnout. Both treatment
      programmes prevented the gastroenteritis which occurred in the controls. The
      growth rates of the treated calves were superior, and their faecal egg output,
      and serum pepsinogen and gastrin concentrations were all substantially lower than
      those of the control calves. The numbers of Ostertagia species larvae on the
      pastures grazed by the treated calves were also lower than on the pastures grazed
      by the control calves.

PMID- 8533222
TI  - Ultrasonographic findings in 11 cows with a hepatic abscess.
AB  - The livers of 11 cows with a hepatic abscess were examined ultrasonographically.
      An abscess was observed in only one intercostal space in three cows, in two
      spaces in five, in three spaces in two, and in four adjacent intercostal spaces
      in one cow. In three cows the abscess was imaged in the caudodorsal aspect of the
      liver in the 11th and 12th intercostal space, in five cows the abscess was
      visible in the central part of the liver in the ninth and 10th intercostal space
      and in the three other cows the abscess was observed in the cranioventral region
      of the liver in the sixth, seventh and eighth intercostal spaces. The abscess had
      a distinct and well developed capsule in nine cows. The content of the abscess
      was echogenic in six cows, anechoic in two, and echogenic with hyperechoic foci
      in three. In four cows, the content of the abscess was partitioned by echogenic
      septa. In one cow, the echogenic content of the abscess was surrounded by a
      narrow anechoic rim of fluid. The diameter of the abscess was 5 to 10 cm in four
      cows, 11 to 15 cm in four, and more than 15 cm in three. In every case the
      diagnosis was confirmed by centesis and aspiration of the abscess which yielded
      pus. Ten of the cows were slaughtered after being examined and the
      ultrasonographic findings were confirmed. In addition, 10 of the cows had other
      lesions which included traumatic reticuloperitonitis, abscessation of the
      reticulum, thrombosis of the caudal vena cava, bronchopneumonia with
      abscessation, reticulo-omasal stenosis, ascites and suppurative omental bursitis.

PMID- 8533223
TI  - Effect of hammer mill screen size and addition of fibre or S-methylmethionine
      sulphonium chloride to the diet on the occurrence of oesophagogastric lesions in
      fattening pigs.
AB  - Four groups of about 86 pigs from a common source were fed a grower diet from 25
      kg to 45 kg liveweight, and then from 45 to 107 kg liveweight they were offered
      one of four diets ad libitum: A) normal commercial feed, ground through a 3 mm
      screen (the control diet), B) the same diet ground through a 6 mm screen, C) the
      control diet to which lucerne meal was added before the diet was ground to
      increase its crude fibre content, and D) the control diet to which was added 400
      ppm S-methylmethionine-sulphonium chloride (MMSC). All the diets were pelleted.
      Approximately 21 per cent of the animals fed the control diet had severe
      oesophagogastric erosions and/or ulcers after slaughter. The addition of 400 ppm
      MMSC decreased (P = 0.066) the proportion of severe oesophagogastric erosions
      and/or ulcers by about 50 per cent compared with the control diet. The diet with
      the higher crude fibre content (but finely ground) did not have a significant
      effect on the proportion of severe oesophagogastric erosions and/or ulcers. There
      was a tendency for the pigs fed the diet ground through a 6 mm screen instead of
      a 3 mm screen, to have fewer severe oesophagogastric erosions and/or ulcers.
      However, there were only small differences between the particle size distribution
      obtained from the wet sieve analysis of the two diets. As a result, the observed
      tendency for a decrease in the proportion of severe oesophagogastric erosions
      and/or ulcers in pigs fed the diet milled through the larger screen size was of
      questionable significance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533224
TI  - Syringomyelia in a stallion.

PMID- 8533225
TI  - Black hair follicular dysplasia in UK bred salukis.

PMID- 8533226
TI  - Production of suilysin, the thiol-activated haemolysin of Streptococcus suis, by
      field isolates from diseased pigs.

PMID- 8533227
TI  - 24-hour service.

PMID- 8533229
TI  - Ritual slaughter.

PMID- 8533228
TI  - 24-hour service.

PMID- 8533230
TI  - 'Stupid calves'.

PMID- 8533231
TI  - Ascites syndrome in a turkey reared above 2000 metres.

PMID- 8533233
TI  - Serological characterisation and antimicrobial susceptibility of Actinobacillus
      pleuropneumoniae strains isolated from pigs in Spain.
AB  - Seventy-one isolates of Actinobacillus pleuropneumoniae isolated from the lungs
      of pigs in outbreaks of pleuropneumonia in Spain were serotyped by indirect
      haemagglutination. Serotype 4 (42.2 per cent), serotype 7 (22.5 per cent) and
      serotype 2 (12.8 per cent) were predominant, whereas serotypes 1, 3, 6, 8, 9, 12
      and untypable isolates were present only in small numbers. Serotypes 1, 2, 4 and
      7 originated mainly from cases of acute pleuropneumonia, whereas serotypes 3, 6,
      8, 9 and 12 were associated with chronically infected herds. The susceptibility
      of the isolates to 20 antimicrobial agents was determined by agar disc diffusion.
      Most were susceptible to cefuroxime, cefaclor, cefazolin, kanamycin, tobramycin,
      gentamicin, oxolinic acid, ciprofloxacin, enoxacin, thiamphenicol, colistin and
      trimethoprim/sulphamethoxazole. Marked resistance was found with amoxicillin,
      ticarcillin, oxytetracycline, doxycycline and metronidazole. Rifampicin,
      fosfomycin and tiamulin were the agents most effective against the isolates
      tested.

PMID- 8533232
TI  - Protection of the bovine fetus from bovine viral diarrhoea virus by means of a
      new inactivated vaccine.
AB  - A model is described for the validation of vaccines designed to protect the
      bovine fetus from bovine viral diarrhoea virus (BVDV). The fetopathic nature of
      the challenge strain of virus was confirmed and the method used to test a
      commercial vaccine (Bovidec) developed from a Compton prototype. Heifers were
      vaccinated two or three times about the time of impregnation and challenged when
      they were between 25 and 80 days of gestation. There was no evidence of a
      viraemia in the heifers after the challenge, or of infection with BVDV of 13
      liveborn calves or two aborted fetuses.

PMID- 8533234
TI  - Ultrasonography of pancreatic neoplasia in the dog: a retrospective review of 16
      cases.
AB  - The history, clinical signs and radiographic and ultrasonographic findings in 16
      dogs with pancreatic neoplasia were reviewed retrospectively. Thirteen of the
      dogs had islet cell carcinoma compatible with insulinoma, one had a pancreatic
      adenocarcinoma and two had secondary invasion of the pancreas, one by a gastric
      carcinoma and one by an intestinal lymphoma. The clinical signs in the 13 dogs
      with insulinoma included collapse in 10 dogs, ataxia in seven, weakness in five,
      and seizures in two. Two of the 16 dogs had jaundice due to biliary obstruction
      by the primary tumour or metastases. The sensitivities for pancreatic neoplasia
      were three of 16 (19 per cent) for radiography and 12 of 16 (75 per cent) for
      ultrasonography; the sensitivities for metastasis were two of 11 (18 per cent)
      for radiography and six of 11 (55 per cent) for ultrasonography. Biliary
      obstruction was detected by ultrasonography in both affected dogs.

PMID- 8533235
TI  - Cutaneous amyloidosis in a horse with lymphoma.
AB  - A horse with malignant lymphoma (histiolymphocytic) and cutaneous amyloidosis is
      described. The lymphoma involved the dura mater of the spinal cord and some of
      the peripheral lymph nodes. Multifocal amyloid deposits were present in the skin
      and subcutis of the ventral abdomen but not within the lymphoma cell infiltrates
      or in the viscera.

PMID- 8533237
TI  - Isolation of an iridovirus-like agent from common frogs (Rana temporaria).

PMID- 8533236
TI  - Latent bovine herpesvirus 1 infection in calves protected by colostral immunity.

PMID- 8533238
TI  - Comparative medicine.

PMID- 8533239
TI  - Maladministration of anthelmintic boluses.

PMID- 8533240
TI  - Transport of animals.

PMID- 8533241
TI  - Suspected venereal spread of Corynebacterium renale.

PMID- 8533242
TI  - Docking and other practices.

PMID- 8533243
TI  - Socialising puppies.

PMID- 8533244
TI  - Socialising puppies.

PMID- 8533245
TI  - A possible mechanism in the pathogenesis of cutaneous lesions in canine
      leishmaniasis.

PMID- 8533246
TI  - Myopathic disorder in a cat.

PMID- 8533247
TI  - A field study of the effect of lameness on mechanical nociceptive thresholds in
      sheep.
AB  - Threshold responses to a mechanical pressure test were measured in two groups of
      adult female sheep taken from 27 flocks in north Devon. The first group consisted
      of 470 healthy sheep and the second of 139 sheep suffering from obvious lameness,
      clinically diagnosed as foot rot. The lame sheep were assessed for the severity
      of the lesion and the level of lameness and assigned a score. In flocks with
      sheep with a severe degree of lameness, the sheep had a significantly lower
      threshold to a mechanical nociceptive stimulus than their matched sound controls
      and their thresholds remained low when tested three months later, after the
      apparent resolution of the foot rot lesion. In flocks where the lame sheep were
      less severely affected there was no difference in the threshold responses to a
      mechanical stimulus between the sound and lame sheep.

PMID- 8533248
TI  - An evaluation of the accuracy of ageing horses by their dentition: a matter of
      experience?
AB  - There is a widely held belief that a horse can be accurately aged by an
      examination of its teeth but this belief has recently been questioned. In this
      study photographs were taken of the dentition of 434 thoroughbreds of known age.
      Four experienced equine clinicians provided estimates of the ages of the horses
      from the photographs. A comparison of the estimated and true ages showed large
      discrepancies in many cases and the discrepancies increased as the horse's true
      age increased. The results show that the ageing of horses from their dentition is
      an imprecise science. It is suggested that written records of the dental features
      are made on each occasion when a dental examination is made and that veterinary
      surgeons advise clients that estimating a horse's age from dental criteria can
      provide no more than an 'informed guess'.

PMID- 8533249
TI  - Spread of lumpy skin disease in Israeli dairy herds.
AB  - Fourteen of the 17 dairy herds in Peduyim, an Israeli village, became infected
      with lumpy skin disease during a period of 37 days in August and September 1989.
      One cow in one neighbouring village and four cows in another neighbouring village
      also became infected, probably through being treated by a veterinarian who
      treated cows in Peduyim. Circumstantial evidence suggests that the original
      infection was brought to Peduyim and spread by stable flies (Stomoxys calcitrans)
      carried by the wind from foci of the disease at El Arish in northern Sinai, or at
      Ismailiya and the Nile delta in Egypt. All the cattle and the small flocks of
      sheep and goats in the village were slaughtered.

PMID- 8533250
TI  - Removal of chip fractures of the femoral trochlear ridges of three horses by
      arthroscopy.
AB  - Clinical and radiographic examinations of three horses with histories of trauma
      and/or wounds to the stifle revealed chip fractures from the medial trochlear
      ridge of the femur of one of them and from the lateral ridges of the femurs of
      the others. The joints were evaluated and the fragments of bone were removed by
      arthroscopy. The results were good in all three horses.

PMID- 8533251
TI  - Chyloabdomen in a neonatal foal.
AB  - A 12-hour-old female standardbred foal developed signs of abdominal pain,
      tachycardia, tachypnoea and fever associated with chylous ascites. Small
      intestinal obstruction was due to segmental, mid-jejunal lymphangiectasia. Post
      mortem examination revealed a lack of communication between afferent and efferent
      lymphatic vessels in the mesenteric lymphocentre, a defect which was suspected to
      be congenital.

PMID- 8533252
TI  - Ingestion of metal objects by ostriches (Struthio camelus).

PMID- 8533253
TI  - Control of BSE: MAFF tightens up on feed production.

PMID- 8533254
TI  - A clinical and ultrasonographic study of the testes and related structures of
      goats and rams after unilateral vasectomy.
AB  - The semen quality, plasma testosterone concentrations and ultrasonographic
      changes were studied for up to 20 weeks after the unilateral vasectomy of two
      adult goats and two rams, and the gross and histological changes were examined
      post mortem. An intact ram and an intact goat served as controls. There was a
      marked decrease in the sperm concentration and the total numbers of sperm per
      ejaculate in both species. However, there seemed to be no effect on ejaculatory
      volume, mass motility and individual motile sperm, percentages of dead and
      abnormal sperm and plasma concentrations of testosterone. Ultrasonographically,
      the epididymal tail lost its characteristic heterogeneous texture and appeared
      enlarged. Anechoic masses, representing sperm granulomata, were visible within
      the epididymal tail of both the rams, and the epididymal head of one of the goats
      and at the cut end of the vas deferens in the other. They were observed as early
      as four to six weeks after surgery and their nature was confirmed post mortem.
      The sequential ultrasonographic changes in the testis and the epididymis are
      described.

PMID- 8533255
TI  - An evaluation of the accuracy of ageing horses by their dentition: changes of
      dental morphology with age.
AB  - Dental features are commonly expected to provide an accurate estimate of a
      horse's age. In this study the dentition of 434 thoroughbreds was photographed
      and the individual dental features documented, the true age of all the horses was
      known. For each dental feature the correlation with true age was determined. The
      eruption of the incisor teeth was the most consistent feature but it was not
      totally reliable. The presence of a hook on the upper corner incisor and
      Galvayne's groove proved to be of no value when estimating age and, of the
      attritional features studied, the dental star showed the highest correlation with
      age. The results show that specific ages cannot be assigned to these dental
      criteria owing to the wide variation between horses, and that as a result the
      estimation of age from dentition can never be precise.

PMID- 8533256
TI  - Incidence of multiple ovulation and multiple pregnancy in mares.

PMID- 8533257
TI  - Estimating the liveweight of sheep from chest girth measurements.

PMID- 8533258
TI  - Anthelmintic resistance in goats in southern Thailand.

PMID- 8533259
TI  - Detection of FeLV antigen.

PMID- 8533261
TI  - Evaluation of homoeopathic treatment.

PMID- 8533260
TI  - Detection of FeLV antigen.

PMID- 8533262
TI  - NVQs and investors in people.

PMID- 8533263
TI  - S zooepidemicus infection and bovine mastitis.

PMID- 8533264
TI  - Transport of animals.

PMID- 8533265
TI  - Veterinary nursing examinations.

PMID- 8533266
TI  - Enhanced karyotype resolution of Cryptosporidium parvum by contour-clamped
      homogeneous electric fields.
AB  - Previous karyotype analysis with contour-clamped homogeneous electric fields
      (CHEF) indicated that the Cryptosporidium parvum karyotype comprises a minimum of
      five chromosomes all less than 1.6 Mb in size. In this study we were able to
      improve the resolution of the karyotype using a modified CHEF gel electrophoretic
      procedure that allows for the routine identification of seven C. parvum
      chromosomes ranging in size from about 0.945 to 2.2 Mb. Our data also suggest
      that an eighth chromosome is present and comigrates with another chromosome at
      about 1.3 Mb.

PMID- 8533267
TI  - Attempts to protect severe combined immunodeficient (scid) mice with antibody
      enriched for reactivity to Cryptosporidium parvum surface antigen-1.
AB  - Cryptosporidium parvum is a protozoal pathogen which infects the gastrointestinal
      epithelium of mammals causing diarrhoea, the duration and severity of which is
      determined by the immunocompetency of the host. Currently, there is no effective
      treatment or prevention. We evaluated the ability of surface antigen-1 (SA-1),
      defined as those antigens recognized by neutralizing mAb 17.41, to elicit a
      protective antibody response when used as an immunogen. A SA-1 enriched fraction
      was obtained by immunoaffinity chromatography and was used to immunize a naive
      Holstein calf. SA-1 immune serum from this calf detected C. parvum epitopes to a
      1:10,000 dilution in a dot blot assay, and sporozoite surface epitopes at a
      1:10,000 dilution in a live immunofluorescence assay. Western blot analysis
      showed that SA-1 immune bovine serum recognized a similar pattern of C. parvum
      antigens as the defining mAb 17.41. Oral passive transfer of SA-1 immune bovine
      serum did not protect severe combined immunodeficient (scid) mice or suckling
      BALB/c mice from initial infection with C. parvum, or terminate a persistent
      infection in scid mice.

PMID- 8533268
TI  - Reactivity of anti-erythrocyte antibody induced by Babesia gibsoni infection
      against aged erythrocytes.
AB  - Effects of ageing treatment of erythrocytes to binding activity of the anti
      erythrocyte antibody(s) in the serum of dogs infected artificially with Babesia
      gibsoni were examined by enzyme-linked immunosorbent assay (ELISA) using fixed
      cell antigen. When erythrocytes made senescent by two artificial ageing
      treatments, one of which was storing erythrocytes at 37 degrees C in medium for
      some days and the other was oxidation of erythrocytes with phenylhydrazine,
      reactivity of anti-erythrocyte antibody(s) in the infected serum to both types of
      treated erythrocytes was increased. These results suggest that such antibody(s)
      could play a role as one of the causes of anemia in canine babesiosis.

PMID- 8533269
TI  - Vaccination of sheep against Schistosoma japonicum with either glutathione S
      transferase, keyhole limpet haemocyanin or the freeze/thaw schistosomula/BCG
      vaccine.
AB  - The protective potential of glutathione S-transferase (GST), keyhole limpet
      haemocyanin (KLH) and the freeze/thaw (F/T) schistosomula/BCG vaccine was
      evaluated against Schistosoma japonicum in the natural sheep host. Groups of ten
      sheep each were vaccinated as follows: Group I: 2 x F/T 30,000 schistosomula+BCG
      3 x 10(8) organisms, with a 2 week interval between vaccinations (F/T 'Low').
      Group II: 3 x F/T 20,000 schistosomula+BCG 3 x 10(8), with 4 week interval (F/T
      'High'). Group III: 2 x GST 0.24 mg+FCA (Freund's complete adjuvant) with 2 week
      interval (GST 'Low'). Group IV: 3 x GST 0.24 mg+FCA, with 4 week interval (GST
      'High'). Group V: 2 x KLH 1.0 mg in phosphate-buffered saline (PBS), with 2 week
      interval (KLH 'Low'). Group VI: 3 x KLH 1.0 mg in PBS, with 4 week interval (KLH
      'High'). Group VII: control (not vaccinated). Specific antibody, detected by GST
      enzyme-linked immunosorbent assay (ELISA) and KLH-ELISA on the day after the last
      vaccination and 1, 2 and 3 weeks post-challenge, was found in all GST- or KLH
      vaccinated groups. The same was found in F/T schistosomula-vaccinated groups
      against crude adult worm antigen (AWA). In Western blotting all GST-vaccinated
      sera recognized 26 kDa and 28 kDa bands on the challenge day and at 3 and 11
      weeks post-challenge. Mean faecal egg counts between Weeks 6 and 10 post
      challenge were reduced in a statistically significant way at five time points in
      the four groups, i.e. 83.38% (P < 0.005) in Group II, 49.29% (P < 0.025) in Group
      III, 47.9% (P < 0.05) and 71.15% (P < 0.01) in Group IV, 52.0% (P < 0.025) and
      66.38% (P < 0.025) in Group VI. On autopsy and perfusion 1 week after the last
      faecal count, adult worm reductions were obtained of 40.36% (P < 0.05) in Group
      I, 37.26% (P < 0.025) in Group II, 24.73% (not significant) in Group III, 35.93%
      (P < 0.025) in Group IV, 27.46% (P < 0.05) in Group V and 33.81% (P < 0.01) in
      Group VI. Mean tissue egg densities were also reduced significantly in Groups
      III, IV and VI, especially in Group IV vaccinated animals. Mean liver egg
      granuloma diameters of the vaccinated groups were found to be less than those of
      the controls but there was no statistical significance.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8533270
TI  - Metacercarial production of Lymnaea viridis experimentally infected with Fasciola
      hepatica.
AB  - Three groups of Lymnaea viridis snails were infected with one, three or five
      Fasciola hepatica miracidia, and their metacercarial production was observed. In
      all groups cercarial shedding commenced in some snails as early as day 27 post
      infection. The duration and pattern of cercarial shedding varied from snail to
      snail in each group. Snails infected with three or five miracidia produced more
      metacercariae than those infected with a single miracidium. The overall
      metacercarial production was influenced by the temperature at which the snails
      were kept during infection.

PMID- 8533271
TI  - Detection of circulating Trichinella spiralis muscle larva antigens in serum
      samples of experimentally and naturally infected swine.
AB  - A follow up study was carried out to determine the kinetics of appearance of
      surface/stichosomal (S/S) components, recently included in the TSL-1 group of
      Trichinella spiralis muscle larva (ML), in serum samples from 13 experimentally
      infected pigs. Detection of circulating antigens in these animals was done by a
      sandwich enzyme-linked immunosorbent assay (ELISA) using T. spiralis specific
      rabbit polyclonal immunoglobulins to capture free antigens and monoclonal
      antibody NIM-M1 to recognize S/S antigens. The assay developed was able to detect
      as little as 35 ng ml-1 of S/S components added to normal pig serum. Antigenemia
      was observed in 54% of the experimentally infected swine with two peaks of
      appearance, one early at 1-4 weeks post-infection (pi) and one late at 10-14
      weeks pi. Specific antibodies against S/S components were demonstrated in serum
      samples from all experimentally infected pigs starting at 3-4 weeks pi. Free
      antigen was also detected in serum samples from naturally infected backyard pigs
      with a sensitivity of 56% compared with 94% when antibody production was
      determined using purified S/S components in an ELISA.

PMID- 8533272
TI  - Efficacy of injectable doramectin in the protection of castrated cattle against
      field infestations of Cochliomyia hominivorax.
AB  - Three studies were conducted in Latin America--one in Venezuela, one in Argentina
      and one in Brazil--using a common protocol to investigate the efficacy of a
      single subcutaneous injection of doramectin in the prevention and control of
      Cochliomyia hominivorax infestations in castrated cattle. In each study, two
      groups of 20-28 animals each were allocated to a treated (T1) or to a control
      (T2) group on the basis of body weights. Animals of T1 received doramectin at 200
      micrograms kg-1 (1 ml per 50 kg) and animals of T2 received saline solution at 1
      ml per 50 kg of live weight. After treatment all cattle were castrated
      surgically. Animals were examined on treatment day and at 2, 4, 6 and 12 days
      post-treatment. At each observation day, the presence of C. hominivorax
      infestations was recorded. Doramectin was 100% effective in the prevention and
      control of screwworm strikes in castrated cattle exposed to continuous field
      infestations of C. hominivorax in tropical and subtropical areas of Latin
      America. Over the 12 day duration of the studies, 85%, 60% and 65% of animals in
      the control groups had infested wounds in Venezuela, Argentina and Brazil,
      respectively. Affected animals required repeated therapeutic treatment, whereas
      none of the doramectin-treated cattle were infested (P < 0.0001). A high
      proportion of the castration wounds in doramectin-treated cattle had the presence
      of characteristic C. hominivorax eggs but none developed into larvae. There were
      no clinical signs of adverse reactions to treatment in any of the three studies.

PMID- 8533273
TI  - The relationship between tick (Amblyomma hebraeum) infestation and immunity to
      heartwater (Cowdria ruminantium infection) in calves in Zimbabwe.
AB  - The occurrence of endemic stability for heartwater (Cowdria ruminantium
      infection) is a controversial issue, because the means by which young cattle and
      other neonatal ruminants become infected and acquire immunity to the disease have
      never been adequately explained. We conducted a study in a heartwater-endemic
      area in southeastern Zimbabwe to investigate the relationships between calf
      immunity to C. ruminatium, infestations of the tick vector Amblyomma hebraeum and
      dam, colostral and calf antibody titres to C. ruminantium. Two groups of cows
      (tick-infested and acaricide-treated) were artificially inseminated and then
      monitored through pregnancy and lactation by means of tick counts and serum
      antibody titres. The calves born to the cows in each treatment group were
      similarly monitored from birth until after weaning, when they were challenged
      with a heartwater stabilate (Ball-3 vaccine). Colostrum was collected from the
      cows on the days that the calves were born. Serum and colostrum samples were
      screened for Cowdria-specific antibodies using an indirect fluorescent antibody
      test. The cows and calves in the acaricide-treated group remained essentially
      tick-free for the duration of the study. The cows in the tick-infested group were
      continuously infested with A. hebraeum, but their calves only became infested
      between 12 and 31 weeks after birth. Cowdria-specific antibodies were detected in
      the sera of the cows and calves and in the colostrum of both treatment groups,
      but the titres were consistently higher in the tick-infested group than in the
      acaricide-treated group. Antibodies, probably of maternal origin since the
      precolostral serum titres were negative, were present in the calves of both
      groups for at least 8 weeks after birth. Between Weeks 24 and 52 postpartum, the
      antibody titres of the tick-infested group of calves were significantly
      correlated with the numbers of A. hebraeum present on the animals. The antibody
      titres of the calves in the acaricide-treated group increased considerably
      following challenge with heartwater stabilate, 60 weeks after birth. No clinical
      heartwater was detected in either group of calves following inoculation of
      stabilate, and it was concluded that the calves in both groups were immune to the
      disease. In the acaricide-treated group, immunity did not correlate with exposure
      to tick-transmitted infections. Hence, we concluded that the calves in both
      groups had probably been infected by vertical transmission around the time of
      birth. Such early infections are likely to have been controlled by maternal
      antibodies or by an unidentified immune mechanism.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8533274
TI  - Isolation of tissue cysts of Toxoplasma, Isospora, Hammondia and Sarcocystis from
      camel (Camelus dromedarius) meat in Saudi Arabia.
AB  - Meat samples were collected from the oesophagus and tongue of 38 camels
      slaughtered at the main abattoir of Al-Ahsa city, Saudi Arabia. Five cats and
      three dogs, conventionally reared and coccidia-free, were caged individually in
      steel cages. Camel meat was pooled, minced and fed to four cats and two dogs. One
      cat and one dog were not fed meat and were kept as noninfected controls. Faecal
      samples from infected and control animals were examined daily for a period of 2
      months after feeding the meat. Three cats fed camel meat passed in their faeces
      oocysts of Toxoplasma gondii, Isospora felis and Isospora rivolta. The fourth cat
      passed only T. gondii and I. felis oocysts. One of the dogs fed camel meat passed
      oocysts of Isospora canis, Hammondia heydorni and Sarcocystis cameli sporocysts.
      The second dog excreted only S. cameli sporocysts.

PMID- 8533275
TI  - Enzyme-linked immunoelectrotransfer blot analysis of excretory-secretory proteins
      of Fascioloides magna and Fasciola hepatica.
AB  - Fasciola hepatica is a parasite of cattle (Bos taurus), but not of white-tailed
      deer (Odocoileus virginianus), while Fascioloides magna is a parasite of white
      tailed deer which also infects cattle as dead-end host. Adult parasites were
      collected from naturally infected white-tailed deer or cattle. Excretory
      secretory proteins (ESP) were obtained from each parasite. Protein banding
      patterns were analysed on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and probed using sera from experimentally infected
      deer of cattle using enzyme-linked immunoelectrotransfer blot (EITB, also known
      as Western blot) analysis. Protein banding patterns of the two species were
      different. EITB analysis of Fascioloides magna ESP using sera from Fascioloides
      magna infected deer or cattle identified three bands of approximately 17, 22 and
      27 kDa of which the 27 kDa antigen cross-reacted with sera from Fasciola hepatica
      infected cattle. EITB analysis of Fasciola hepatica ESP probed with sera from
      Fasciola hepatica infected cattle identified three bands of approximately 15, 26
      and 46 kDa. The 46 and 26 kDa ESP cross-reacted with sera from Fascioloides magna
      infected cattle, but not with sera from Fascioloides magna infected deer. The
      band at 15 kDa which reacted specifically for Fasciola hepatica infected cattle
      sera consisted of two protein bands close to each other as seen on the SDS-PAGE
      gel. The EITB reaction at approximately 17 kDa and 22 kDa of Fascioloides magna
      ESP, and at approximately 15 kDa of Fasciola hepatica ESP can be used for species
      specific diagnosis.

PMID- 8533276
TI  - Factors influencing the transmission and incidence of tropical theileriosis
      (Theileria annulata infection of cattle) in Morocco.
AB  - A longitudinal epidemiological investigation of tropical theileriosis was carried
      out in an endemic region of Morocco during the 1991 disease season. This involved
      approximately 220 cross-bred cattle on 15 farms. Data were collected on the
      frequency of existing infections, the size of the vector tick population and the
      incidences of new infections and clinical disease, and these were then analysed
      using statistical models. The prevalence of subclinically infected carriers of
      Theileria annulata, the number of adult Hyalomma detritum, the vector, and the
      probability of becoming newly infected with T. annulata increased significantly
      with the age of cattle, although the age effect on new infections may be a result
      of increased tick numbers on older animals. The probability of clinical disease
      in newly infected cattle was not significantly influenced by age or by the number
      of adult ticks, but was significantly positively associated with the cattle
      population on the farm. The number of H. detritum nymphs counted on cattle in the
      autumn was related significantly to the previous adult tick count on the same
      animal.

PMID- 8533277
TI  - Exoantigens of an attenuated strain of Babesia bovis used as a vaccine against
      bovine babesiosis.
AB  - Bovine babesiosis caused by Babesia bovis remains a significant constraint to
      beef and milk cattle production throughout the world. Exoantigens released by the
      parasites in culture supernatants are a potential source of antigen to induce
      protective immunity. An attenuated strain of B. bovis from Brazil, catalogued as
      BbUFV1, was maintained in vitro by the MASP method, and exoantigen-containing
      supernatant fluids were collected daily to form a pool representing a 72-h
      culture cycle for preparation of the vaccine. Exoantigen concentration was
      estimated using a two-site EIA. Three groups of susceptible non-splenectomised
      male Bos taurus cattle, 14 months old, were used. Group A (vaccinated) received
      two subcutaneous immunizations with a 21-day interval of B. bovis supernatant,
      content 6500 EIA units of exoantigens plus 1.5 mg saponin, and Group B (adjuvant
      control) received two injections of adjuvant alone. Four weeks after the second
      immunization, Groups A, B and C (control) were challenged intravenously with
      10(8) virulent parasites of a heterologous B. bovis strain. The results showed
      that exoantigens present in in vitro cultures can induce a high degree of
      protection against virulent heterologous challenge exposure. In Group A only one
      animal showed discrete parasitaemia; all developed a fever and slight decreases
      in PCV, with a rapid return to normal values. One animal of Group B died; the
      survivors showed fever, anaemia and parasitaemia. All animals of Group C died
      between 7 and 13 days after challenge. Vaccination elicited both humoral and cell
      mediated immune responses. In Group A, after the challenge, the maximum antibody
      titer was 12,800. When vaccinated, cattle were tested at the moment of challenge
      for B. bovis-specific cell-mediated immunity by the monocytemigration inhibition
      test. A mean inhibition index of 60 +/- 0.33 was observed. Preliminary Western
      blot analysis of the immunogen revealed at least four proteins of molecular
      weight ranging between 30 and 160 kDa.

PMID- 8533278
TI  - Detection of Cryptosporidium oocysts in extra-intestinal tissues of sheep and
      pigs.
AB  - Extra-intestinal infections by Cryptosporidium parvum have been detected in pigs
      and sheep. Detection was carried out by imprints of the mucosa of different
      organs and viscera in 55 sheep and 57 pigs slaughtered at three abattoirs in
      Zaragoza (northeast Spain). Imprints were stained by using a modified Ziehl
      Neelsen technique. In addition to intestinal infections, cryptosporidial oocysts
      were found in the gall-bladders of two pigs which were 2 months old, and in some
      organs of sheep aged 5 days or more, including the gall-bladder (5), mesenteric
      lymph nodes (2), trachea (7), lung (3) and the uterus of one lamb.

PMID- 8533279
TI  - The influence of energy intake on the pathophysiology of Trypanosoma congolense
      infection in Scottish blackface sheep.
AB  - The intensity of parasitaemia, degree of anaemia, live body weight gains and
      blood biochemical changes were measured in two groups of Scottish Blackface sheep
      infected experimentally with Trypanosoma congolense and allowed either a high
      (9.9 MJ metabolisable energy (ME) day-1) or a low (6.1 MJ ME day-1) energy
      intake. It was observed that infected animals on the low energy intake had a
      longer mean prepatent period, but following patency they developed more severe
      anaemia and greater growth retardation than those on the high energy intake. Both
      infected groups exhibited significant reductions in serum total lipids,
      phospholipids, plasma cholesterol and albumin. However, these changes were more
      severe in the animals on the low energy intake than in those on the high energy
      intake. It was concluded that adequate energy nutrition enhances the ability of
      infected animals to withstand the adverse effects of infection, by promoting body
      weight gains and moderating the severity of the pathophysiological changes
      associated with ovine trypanosomosis.

PMID- 8533280
TI  - Low molecular weight Cooperia oncophora antigens: characterization and humoral
      immune responses in calves mono-infected with 100,000 infective larvae.
AB  - Characteristics of the humoral immune response of Cooperia oncophora-infected
      calves to low molecular weight antigens of C. oncophora were studied.
      Immunoblotting with sera obtained from calves 6 weeks after a single oral
      infection with 100,000 third-stage (L3) C. oncophora larvae revealed several
      corresponding antigenic fragments between adult worms and the fourth-stage (L4)
      larvae. No reactivity in the immune sera was found against the L3 stage. A
      previously defined complex of low molecular weight proteins (12-15 kDa) was found
      on both L4 and adult Cooperia stages, but not on the L3 stage. C. oncophora
      adults differed from the L4 larvae at the 31/32 and 37 kDa level. Several adult
      and L4 proteins were bound by biotinylated Concanavalin A, as was also true for
      L3 proteins. A 31/32 kDa glycoprotein of adult worms was recognised by a
      monoclonal antibody with specificity for phosphorylcholine. Using monoclonal
      antibodies in ELISA and Western blotting, the serum antibody response of C.
      oncophora-infected calves to adult worm antigen was almost entirely IgG1. Binding
      of the IgG1 antibodies was restricted to a complex of reduced 12-15 kDa
      protein(s) and a 27 kDa fragment of adult worms. The data suggest that the
      systemic humoral immune response of calves during a primary infection with C.
      oncophora consists mainly of an IgG1 response, and is directed to a non
      glycosylated Cooperia protein (molecular weight estimated at 12-15 kDa under
      reducing conditions and 18 kDa under nonreducing conditions). This protein is
      probably present in both L4 larvae and adults. Since it was not bound by immune
      sera from calves mono-infected with several other nematodes, the 12-15 kDa
      protein complex may represent a Cooperia-specific component that can be used for
      serodiagnosis.

PMID- 8533281
TI  - Systemic antibody responses of calves to low molecular weight Cooperia oncophora
      antigens.
AB  - The systemic antibody responses to adult Cooperia oncophora antigen were studied
      using sera obtained from calves during a 6-week period following a single oral
      infection with either 20,000 or 100,000 third-stage C. oncophora larvae. Dose
      dependent increasing titres of IgG binding complete adult Cooperia antigen were
      found in the sera of Cooperia-infected calves. SDS-gel electrophoresis under
      reducing conditions, followed by Western blotting, revealed that the increase of
      IgG binding Cooperia antigens could be attributed mainly to specific binding of
      IgG to a complex of 12-15 kDa protein fragments of Cooperia adult antigen. This
      protein may represent a Cooperia oncophora-specific component that can be used
      for serodiagnosis.

PMID- 8533282
TI  - Dose titration of moxidectin oral gel against gastrointestinal parasites of
      ponies.
AB  - Moxidectin was tested as an oral gel formulation during a controlled test
      performed to evaluate dosages against equine gastrointestinal parasites. Four
      groups of ten ponies were used. Ponies ranged from 1 to 20 years of age and were
      naturally infected in southern Louisiana or Mississippi. Fecal exams and fecal
      cultures were performed on all ponies to determine the strongyle egg counts and
      the percent distributions of large and small strongyles. Following these
      determinations, ponies were allocated to replicates of four ponies to provide an
      even distribution of strongyle infection, age, weight and gender. Members of each
      replicate were then randomly assigned to one of four treatment groups. The doses
      tested were 300, 400 and 500 micrograms kg-1 body weight. The oral gel vehicle
      alone served as control. Treatments were administered behind the tongue and the
      ponies were observed continuously for 4 h for any adverse reactions; thereafter,
      ponies were observed at least twice daily. Necropsy examinations were performed
      14 days post-treatment for the recovery and identification of any parasites
      present. Moxidectin, at all doses tested, was 100% efficacious against adults of
      Strongylus vulgaris, Strongylus edentatus, Triodontophorus spp. and 22 species of
      small strongyles. Moxidectin was also 100% efficacious against larvae of
      Strongylus edentatus and Oxyuris equi, greater than 94% efficacious against
      Strongylus vulgaris larvae and Oxyuris equi adults at 14 days post-treatment.
      Moxidectin proved highly efficacious against luminal small strongyle larvae (>
      99.9% against L4 and > 92% against L3) and moxidectin demonstrated some efficacy
      against encysted small strongyle larvae as well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533283
TI  - A method for in vitro determination of the acaricidal effect of ivermectin using
      Sarcoptes scabiei var. suis as test organism.
AB  - An in vitro assay for the acaricidal effect of ivermectin is described. The test
      is based on the migration ability and survival of Sarcoptes scabiei var. suis
      mites on the surface of agar gels containing the acaricide. The effect of a given
      concentration of ivermectin is expressed as an activity index (AI) for the mites,
      calculated from observed migration and mite survival after 24 h of incubation. In
      order to allow a concentration-effect curve to be based on true values of the
      acaricide, a method for the determination of ivermectin in agar gels was
      developed. Employing this method, ivermectin was demonstrated to be stable in the
      gels at room temperature for a month, thus allowing storage of gels for later
      use. The test was found to be accurate, sensitive, easy to carry out and
      applicable for routine determinations. The lower threshold for acaricidal effect
      was found to be 50-100 ng ml-1 with the AI showing a reverse linear dependence on
      the log concentrations above this value.

PMID- 8533284
TI  - The efficacy of Diflubenzuron against the body louse (Damalinia limbata) of
      Angora goats.
AB  - The efficacy of an insect growth regulator, Diflubenzuron, to control biting lice
      (Damalinia limbata) on Angora goats was investigated. Lice on goats which were
      dipped in a concentration of 625 g Diflubenzuron to 1,000 1 water and then kept
      in quarantine was eradicated after a single treatment. Nymphs remained present on
      these goats up to 4 weeks and adult lice up to 8 weeks post-treatment. A single
      treatment provided greater than 90% reduction in nymphal stages from Week 6 to
      Week 16 post-treatment in treated goats continuously exposed to reinfestation.
      The treatment reduced adult louse infestations on these goats by 78-94% through
      Weeks 6-16 post-treatment. At the end of the trial (24 weeks post-treatment),
      these goats had 88% fewer nymphs and 84% fewer adult lice compared with untreated
      control goats.

PMID- 8533285
TI  - The effects of continuous and intermittent delivery of antigens of Boophilus
      microplus on the development of murine antibodies.
AB  - Protective antigens solubilised from the membranes of the midgut (LI-GM) of the
      adult cattle tick Boophilus microplus were delivered to mice either continuously
      for up to 4 weeks from osmotic pumps implanted subcutaneously or intermittently
      in a pulsatile fashion by injections or by a combination of both modes of
      delivery. The effects of delivery profile on antigen specific antibody levels and
      avidity were compared. LI-GM delivered either by three injections (weeks 0, 2 and
      4), or continuously from osmotic pumps (over 4 weeks) induced similar levels of
      antibodies in mice. The mode of delivery of LI-GM when in the presence of the
      adjuvant Quil A did not generally affect either the level or the avidity of the
      antibody response; indeed a single injection of LI-GM in the presence of Quil A
      stimulated an immune response similar to that induced by several combinations of
      pulsatile and of continuous delivery where mice were exposed to antigen and
      adjuvant for up to 4 weeks. LI-GM incubated at 37 degrees C in vitro and in vivo
      for periods from 4 h to 14 days was partly degraded into low molecular weight
      (less than 29 kDa) components. The immunogenicity of LI-GM incubated in vitro for
      4 h was significantly decreased, although its antigenicity was not affected after
      incubation for up to 14 days. In conclusion, delivery of LI-GM continuously from
      osmotic pumps demonstrated that single-step immunisation of mice with tick
      antigens was feasible. However, it was also demonstrated that the continuous
      delivery of antigen was only advantageous (i.e. potential for a decrease in the
      number of times an animal must be handled) compared with delivery by injections
      when no adjuvant was used. Further work is necessary to establish the effect
      antigen degradation has in limiting the immune response resulting from continuous
      delivery of antigen from osmotic pumps.

PMID- 8533286
TI  - Monoclonal equine IgM and IgG immunoglobulins.
AB  - In order to define equine immunoglobulins (Igs) and to produce monoclonal
      reference Igs we fused equine peripheral blood mononuclear cells with X63-Ag8.653
      non Ig producing murine myeloma cells. A total of 29 equine Ig producing equi
      murine heterohybridomas were obtained, of which ten expressed equine Ig for more
      than 3 months. One of these heterohybridoma lines produced monoclonal IgM, an
      equine isotype which has not been available in monoclonal form before. Four lines
      secreted equine IgG of two distinct Ig heavy chain types as assessed by the
      molecular weight (MW), while the remaining five lines expressed only equine Ig
      light chains. A sixth Ig light chain expressing variant was obtained by cloning
      of one of the IgG producing heterohybridoma lines. These monoclonal IgGs were
      compared with previously described equine IgG monoclonal antibodies (mabs) by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). According
      to their MW we identified five groups of gamma-chains and four groups of Ig light
      chains.

PMID- 8533287
TI  - Serum antibody responses of cattle to iron-regulated outer membrane proteins of
      Pasteurella haemolytica A1.
AB  - Serum antibody responses to the 70, 77, and 100 kDa iron-regulated outer membrane
      proteins (IROMPs) of Pasteurella haemolytica A1 were studied in cattle vaccinated
      with outer membrane protein (OMP) enriched outer membrane fraction, IROMP
      enriched outer membrane fraction or live P. haemolytica. Vaccination with an
      IROMP-enriched outer membrane fraction stimulated antibodies to the 70 kDa IROMP,
      whereas vaccination with live P. haemolytica stimulated antibodies to the 70 and
      77 kDa IROMPs. In a second experiment, sera were used from cattle vaccinated with
      live or killed P. haemolytica and subsequently challenged. Significant antibody
      responses to OMP- and IROMP-enriched outer membrane fractions were detected by an
      enzyme-linked immunosorbent assay (ELISA) for cattle vaccinated with bacterins or
      live P. haemolytica. Regression analysis indicated significant correlations
      between high antibody responses to the OMP- or IROMP-enriched fraction and
      resistance to challenge. Antibody responses to the 70 and 77 kDa IROMPs were
      significantly greater for the live P. haemolytica vaccinates than for PBS control
      vaccinates. There was no significant correlation between antibody responses to
      individual IROMPs and resistance or susceptibility to challenge. These data
      suggest that antibodies to IROMPs alone are probably not responsible for
      protective immunity against pneumonic pasteurellosis. Antibodies to IROMPs,
      however, in conjunction with antibodies to other surface antigens probably
      enhance immunity to P. haemolytica challenge.

PMID- 8533288
TI  - Effects of in vitro supplementation of bovine mammary gland macrophages and
      peripheral blood lymphocytes with alpha-tocopherol and sodium selenite:
      implications for udder defences.
AB  - vitamin E and selenium have been observed to enhance the functions of bovine
      mammary gland macrophages and peripheral blood lymphocytes. In vitro
      supplementation with these compounds enhanced the production of neutrophil
      chemotaxins by macrophages stimulated with opsonised Staphylococcus aureus.
      Supplementation also enhanced the proliferation of peripheral blood lymphocytes
      in response to stimulation with concanavalin A but not to phytohaemagglutinin or
      pokeweed mitogen. There was no evidence of additive or synergistic effects of
      vitamin E and selenium. Results suggest that supplementation of cattle may
      optimise resistance to mastitis by enhancing the functions of resident macrophage
      and lymphocyte populations.

PMID- 8533289
TI  - The immunopathology of unilateral vasectomy in the ram.
AB  - This study investigated the relationship between the local (spermatic granuloma)
      and systemic events after unilateral vasectomy in six rams. Spermatic
      microgranulomas were first observed at 4 weeks post vasectomy (PV), at which time
      lymphocytes, chiefly CD4+ (helper/inducer) cells, were incorporated into the
      periphery of the phagocytic wall. Although plasma cells accumulated around blood
      vessels near these early granulomas, they were not incorporated into them. All
      sectioned vas deferens contained additional microscopic spermatic granulomas away
      from the point of sectioning, as did one-third of cauda epididymides on the
      vasectomised side. There were significant (P < 0.001) increases in T-lymphocytes,
      especially CD4 cells and plasma cells (chiefly IgG-containing) within the
      granulomas at each successive PV interval. Concurrent enzyme-linked immunosorbent
      assay indicated initial presence of IgG and IgM antisperm antibody in serum
      between 2 and 4 weeks PV. There were significant increases of IgG (P < 0.01) and
      IgM (P < 0.001) throughout the experiment but IgA antisperm antibody was
      negligible.

PMID- 8533290
TI  - Immunohistochemical detection of canine leucocyte antigens by specific monoclonal
      antibodies in canine normal tissues.
AB  - This report describes the immunocytochemical detection and distribution of
      different canine leucocytes antigens (Thy-1, CD5, CD4, CD8, MHC-II and B-cell
      antigen) by means of monoclonal antibodies (mAbs) in frozen tissue sections of
      lymphoid organs of the dog. CD5 is expressed exclusively by T lymphocytes. Thy-1
      is expressed by T-lymphocytes and in a variety of non-lymphoid tissues. The mAb
      against canine MHC-II could detect B and T lymphocytes, macrophages, fibroblasts
      and antigen presenting cells. The CD4 antigen is expressed on many lymphocytes of
      the T-dependent areas of lymph organs and is also expressed by certain antigen
      presenting cells. CD8 is expressed in a minor proportion of T cells. The mAb
      against B cells detected lymphocytes in lymphoid follicles and epithelial cells
      of the thymic medulla.

PMID- 8533291
TI  - The effect of storage on immunophenotyping of sheep peripheral blood lymphocytes
      by flow cytometry.
AB  - We have shown that when a whole blood method of cell staining is used for flow
      cytometric analysis of sheep lymphocytes (i.e. red cell lysis after addition of
      antibody), staining may be delayed for up to 48 h after blood collection without
      significant effect on expression of CD4, CD5, CD8 or B cell markers. If cells
      were stained immediately after blood collection, using the same whole blood
      method, and then fixed with paraformaldehyde, cell samples could be stored for 24
      h without change in marker expression. However, by 7 days there was a significant
      decrease in the percentage of cells expressing CD8, T19 and B cell markers.
      Cryopreservation prior to staining was found to markedly affect the expression of
      all cell surface markers investigated. These results indicate that storage of
      sheep blood prior to flow cytometric analysis is feasible but may affect the
      results obtained. Thus is it important to standardise the handling of samples,
      especially when comparative studies are being undertaken.

PMID- 8533292
TI  - Influence of flumequine on in vivo mitogen responses of European eel (Anguilla
      anguilla L., 1758) lymphoid cells.
AB  - The influence of flumequine on mitogen induced lymphoid cell proliferation in
      European eels (Anguilla anguilla L., 1758) was studied. For this purpose an in
      vivo test, using peroral drug administration followed by successive
      intraperitoneal injections with concanavalin A (ConA) or bacterial
      lipopolysaccharides (LPS) and 5-bromo-2'-deoxyuridine, was applied. Direct
      counting of proliferated cells in blood smears revealed that flumequine possesses
      mitogenic properties. A synergistic and an antagonistic effect of the drug was
      observed after LPS and ConA stimulation, respectively. Flow cytometric analysis
      of peripheral blood lymphoid cells showed a significant reduction of the mean
      proportion surface immunoglobulin positive cells in the flumequine-treated
      animals. It is concluded that flumequine enhances proliferation of lymphoid cells
      (probably surface immunoglobulin negative cells) in eel under the present
      experimental conditions.

PMID- 8533293
TI  - Genetic variation in susceptibility to Trypanoplasma borreli infection in common
      carp (Cyprinus carpio L.).
AB  - Gynogenetic reproduction of homozygous females, or crossbreeding two homozygous
      animals, results in fish lines without genetic variation. Hybrid crosses are
      expected to express a more stable development than homozygous lines, the latter
      may have an important value for gaining insight into genetic components of host
      resistance to parasite infection. We examined the antibody response of carp
      (Cyprinus carpio L.) to infection with Trypanoplasma borreli. Outbred carp
      responded with a production of specific antibodies, but highly susceptible
      isogenic hybrid carp did not. This suggests an apparent relationship between
      susceptibility and the lack of specific antibody production. This relation was
      partially confirmed by the passive transfer of immunity with immune plasma. In
      addition, two isogenic homozygous carp lines were highly susceptible to the
      trypanoplasm (100% mortality), in contrast with outbred carp, the majority of
      which survived infection. None of the carp in either homozygous carp line
      produced an antibody response to parasite-unrelated antigen (DNP-KLH). This
      suggests that the low antibody response was not entirely due to a poor state of
      health, but that these carp have a genetically predetermined low antibody
      response.

PMID- 8533294
TI  - Histopathology of the thymus in Saprolegnia-infected wild brown trout, Salmo
      trutta L.
AB  - A comparative analysis was made of the thymic cytoarchitecture of healthy and
      Saprolegnia-infected wild brown trout. In Saprolegnia-infected fish, even when
      the thymus was not invaded by fungal hyphae, the thymic architecture was lost
      without signs of regionalization. Intercellular oedema, some thymocytes,
      hypertrophic and degenerated epithelial cells and increased phagocytic activity
      were also observed. In thymi invaded by the fungus, hyphae occurred isolated or
      in close apposition to epithelial cells, and the thymic disorganization was more
      noticeable. Most thymocytes were pyknotic and both epithelial cells and
      macrophages contained engulfed dead cells. However, no inflammatory response to
      the fungal invasion was observed. These results confirm the immunodepressed
      condition of Saprolegnia-infected wild brown trout previously observed in
      peripheral lymphoid organs. We discuss the secretion of fungal products and/or
      the high levels of corticosteroids observed in these fish as possible origins of
      the condition.

PMID- 8533295
TI  - A new fluorochromasia method using a fluorescence microplate reader for assay of
      cytotoxic activity of carp leucocytes.
AB  - A new fluorochromasia method using a fluorescence microplate reader has been
      established to assay spontaneous cytotoxic activity of carp leucocytes. This
      method is characterized by using propidium iodide (PI) for staining dead target
      cells and a fluorescence microplate reader for measurement of the fluorescence of
      PI. K562 as target cells were prepared in 96-well flat-bottom microplates, and
      carp leucocytes were added as effector cells. After 2.5 h incubation, PI was
      added to each well. After an additional 1.5 h incubation, fluorescence of each
      well was measured. Correlation between this method and 51Cr-release assay was
      obtained. The results demonstrated that this new fluorochromasia method can be
      used to assay cytotoxic activity of carp leucocytes.

PMID- 8533296
TI  - A possible linkage between gonadal hormones, serum and uterine levels of IgG of
      dairy cows.
AB  - We have investigated the possible linkage between serum and uterine fluid
      immunoglobulin G (IgG) levels and the hormonal status of the cow. In cycling cows
      there was a significant (P < 0.01) drop in average (of 4 consecutive days) serum
      IgG levels, from 36.4 +/- 6.7 mg ml-1 during the luteal phase of the estrous
      cycle to 28.3 +/- 5.3 mg ml-1 during and around estrus. In prepartum cows, there
      was a significant drop (P < 0.01) from an average of 37.6 +/- 3.7 mg ml-1 from 5
      consecutive days, i.e. 11-7 before parturition, to 28.0 +/- 5.5 mg ml-1 on the
      day of parturition. Total IgG in the uterine fluid ranged from 30 to 115 mg in
      one horn and from 24 mg ml-1 to 70 mg ml-1 in the other horn during the luteal
      phase, but was essentially undetectable at estrus. The drop in serum and uterine
      IgG occurred concomitantly with the drop in peripheral serum progesterone, from 2
      3 ng ml-1 at the luteal phase, and 11-7 days before calving to less than 0.5 ng
      ml-1 around estrus and calving. Data suggest a possible linkage between steroid
      hormone and IgG levels.

PMID- 8533297
TI  - Purification of canine alpha-fetoprotein and alpha- fetoprotein values in dogs.
AB  - Canine alpha-fetoprotein (AFP) was purified by a two step method. Anti-dog AFP
      antiserum was produced by immunizing rabbits with canine fetal serum proteins
      that failed to bind to an anti-dog whole adult serum affinity column. Canine AFP
      was then purified from amniotic fluid using affinity chromatography with anti-dog
      AFP antiserum. The bound protein was then eluted and further purified by passage
      through an anti-dog whole adult serum column. The non-binding protein's purity
      and specificity was confirmed by immunoelectrophoresis, double-diffusion, sodium
      dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and cross
      reactivity with anti-human AFP. The molecular weight of canine AFP was
      approximately 66,000 by SDS-PAGE. Normal adult dogs had serum AFP levels of 7-63
      ng ml-1. Levels of AFP were not altered by pregnancy but did show a small peak 2
      days following parturition. Newborn puppies had serum AFP levels of 14.08 +/-
      5.94 mg ml-1 at birth. By 1 week of age, serum AFP had fallen to 0.766 +/- 0.758
      mg ml-1. AFP values in newborn puppies are thus considerably higher than those
      previously reported in humans, pigs and cattle.

PMID- 8533298
TI  - Effect of bursal anti-steroidogenic peptide (BASP) on cortisol biosynthesis in
      ACTH-stimulated canine adrenocortical carcinoma cells in vitro.
AB  - Previous studies from our laboratory have demonstrated that bursal anti
      steroidogenic peptide (BASP) inhibits progesterone biosynthesis from ovine
      luteinizing hormone-stimulated chicken ovarian granulosa cells. In the present
      investigation, we evaluated the efficacy of BASP for reducing cortisol secretion
      from normal canine adrenocortical cells and neoplastic adrenocortical cells from
      a dog with Cushing's syndrome. Treatment of adrenocortical cells derived from
      either normal healthy dogs or a cushingoid dog with adrenocorticotropic hormone
      (ACTH; 0-10 nM) caused an approximately two-fold increase in cortisol production
      from both normal or tumor derived adrenocortical cells. Small but significant
      decreases (up to 34%) in cortisol production were observed from normal and tumor
      derived canine adrenocortical cells when exposed to increasing concentrations of
      BASP (0.0-0.15 bursal equivalents; BEQ). Incubation of adrenocortical carcinoma
      cells or normal adrenocortical cells with ACTH (0-10 nM) and BASP (0.0-0.15 BEQ)
      increased cyclic AMP formation up to 2.5-fold. Interestingly, BASP suppressed
      basal cortisol production from tumor derived adrenocortical cells to normal
      levels when compared to the basal cortisol levels from normal derived
      adrenocortisol cells. Data from the present studies indicate that BASP is capable
      of suppressing basal and ACTH-stimulated cortisol production from normal or tumor
      derived adrenocortical cells in vitro. The possible clinical efficacy of
      homologous canine BASP on canine adrenal function or chicken BASP in other
      species of animals remains to be evaluated.

PMID- 8533299
TI  - Effect of surface antigen-1 (SA-1) immune lymphocyte subsets and naive cell
      subsets in protecting scid mice from initial and persistent infection with
      Cryptosporidium parvum.
AB  - We tested the hypothesis that adoptive transfer of immune spleen cell subsets
      from Cryptosporidium parvum antigen immunized, immunocompetent BALB/c mice would
      prevent initial infection or terminate persistent infection in severe combined
      immunodeficient (scid) mice. Cell donor mice were immunized with either
      solubilized C. parvum oocysts and sporozoites (positive control) or a surface
      antigen-1 (SA-1) enriched C. parvum antigen fraction. Both groups of BALB/c cell
      donor mice immunized with C. parvum antigens had increased antibody titers and
      lymphoproliferative responses when compared with negative control mice injected
      with phosphate buffered saline and adjuvant. Intravenous adoptive transfer of 5 x
      10(6) cells of each cell subset (spleen cells, CD4 T and B lymphocytes, CD4 T
      lymphocytes or B lymphocytes) derived from immunized adult BALB/c donor mice did
      not protect scid mice against initial infection of the gastrointestinal
      epithelium with C. parvum, despite flow cytometric evidence of CD4 T lymphocyte
      engraftment in the spleen and detectable levels of C. parvum-specific serum
      antibody. In contrast, intravenous injection of either naive or immune CD4 T and
      B lymphocytes combined, or CD4 T lymphocytes alone, terminated persistent C.
      parvum infection in scid mice. Intestinal infectivity scores were significantly
      reduced by 9 days post-engraftment in all groups and continued to decline
      throughout the remainder of the experiment. Flow cytometric analysis demonstrated
      significantly increased CD4 T lymphocytes in the spleens of recipient scid mice
      when compared with infected scid mice receiving no cells. Cryptosporidium parvum
      specific antibody was detected on day 12 post engraftment in mice receiving SA-1
      immune CD4 T and B lymphocytes but was not detectable in mice receiving naive
      cell subsets.

PMID- 8533300
TI  - IgM, IgA, IgG1 and IgG2 specific responses in blood and gut secretion of calves
      fed soyabean products.
AB  - Calves fed soya proteins may develop severe gastrointestinal disorders. Whether
      these are predominantly associated with particular Ig subclasses and (or) dietary
      proteins remains unclear. Therefore, antibody responses to soyabean protein were
      analysed by dot- and blot-immunobinding in plasma and intestinal mucous
      secretions. One-month-old calves were fed for 2.5 months liquid diets based on
      skim milk powder (SMP) or a mixture (2:3, protein basis) of whey and soyabean
      products including a low antigenic hydrolysed soya protein isolate (HSPI) and a
      highly antigenic heated soya flour (HSF). Specific antibodies (Abs) of the main
      isotypes (IgM, IgA, IgG1, IgG2) were characterised by immunostaining of samples
      which had been previously incubated with nitrocellulose sheets coated with SMP,
      HSPI or HSF extracts. Plasma collected before feeding experimental diets showed
      very little specific Abs. By contrast, 2.5 months later, a three-fold increase (P
      < 0.05) in IgG1 and IgA titres against HSF antigens was observed in calves fed
      HSF compared with those fed the control or HSPI diet. IgG1 immunoblotting
      revealed many protein bands from soya in the molecular range of 22-32 and 38-42
      kDa. Immunorecognition of specific proteins from SMP and HSPI remained low and
      similar among animal groups. Specific IgM, IgA and IgG1 titres against HSF, and
      to a lesser extent HSPI, were significantly higher (P < 0.05) in jejunal mucous
      secretion of calves fed HSF compared with other groups. Secretions from calves
      fed HSF bound to many soyabean proteins in the range of 17-23 and 26-38 kDa, with
      similar patterns for IgA and IgG1. By contrast, only weak bands were found for
      IgM and IgG2 in all groups of calves. Thus, calves fed antigenic HSF do present
      specific Abs including IgG1 and IgA isotypes, both systemically and locally.
      Therefore, IgG1 and (or) IgA rather than IgM and IgG2 Abs may be preferred for
      assessing the immunogenicity of soyabean products in calves. Interestingly,
      soyabean immunogenicity was drastically reduced by adequate proteolysis.

PMID- 8533301
TI  - B and T lymphocytes are enhanced in the gut of piglets fed heat-treated soyabean
      proteins.
AB  - Gut immune responses have been suspected in food hypersensitivity reactions such
      as those to soyabean proteins in early-weaned piglets. The present study examines
      the lymphoid cell subset distribution in piglets fed heat-treated (HTSP) or
      ethanol-treated soyabean proteins (ETSP). Duodenal cryosections of 4-week-old
      HTSP piglets (n = 10) and ETSP piglets (n = 8) were analysed for IgA, IgM, IgG1
      and IgG2 positive cells, CD2, CD4, CD8, WC1 T cell positive antigens using
      immunohistochemical peroxidase reactions. Densities of IgM+ and IgA+ cells were
      three times and, IgG1+ and IgG2+ six times higher in the lamina propria of HTSP
      piglets compared with ETSP (P < 0.05). Increased CD2+ T cells were accounted for
      by a rise in both CD4+ and CD8+ T cell subsets in the lamina propria (P < 0.01)
      as well as in the epithelium of the duodenal mucosa of piglets fed HTSP. The
      density of the WC1+ T cell subset in the epithelium was significantly higher in
      HTSP than in ETSP piglets (P < 0.01). Immune reactions in the duodenal mucosa,
      involving both B and T lymphocytes may be related to atrophy of the duodenal
      villi in HTSP piglets.

PMID- 8533302
TI  - Isotype-specific antibody responses to bovine herpesvirus 1 in sera and mucosal
      secretions of calves after experimental reinfection and after reactivation.
AB  - Isotype-specific antibody responses to bovine herpesvirus 1 (BHV1) were measured
      in sera, nasal, ocular and genital secretions of calves that were reinfected with
      BHV1 and 6 weeks later treated with corticosteroids to reactivate putative latent
      virus. After reinfection and after reactivation, no BHV1-specific IgM antibody
      response was detected. The serum IgA response was only transiently detectable
      after reinfection and again appeared rapidly after reactivation in most calves.
      Most calves showed an increase in nasal and ocular IgA titres after reinfection
      and reactivation; some calves also had IgA antibodies in genital secretions. A
      salient finding was that after reinfection and reactivation more calves showed a
      serum IgA response than virus shedding or an increase in serum IgG1 or IgG2
      titres. This suggests that the serum IgA response would be the most sensitive
      indicator to detect BHV1 reinfection and reactivation. No correlation was found
      between nasal IgA titre at the time of reinfection or corticosteroid treatment
      and the period of virus shedding, suggesting that nasal IgA does not play a major
      role in protection against reinfection with BHV1.

PMID- 8533303
TI  - Comparative performance of the enzyme-linked immunosorbent assay (ELISA) and
      conventional assays in the diagnosis of bovine brucellosis in Argentina.
AB  - The FAO/IAEA enzyme-linked immunosorbent assay (ELISA) kit for the diagnosis of
      bovine brucellosis was compared in Argentina with two screening tests, the Rose
      Bengal (RB) and the buffered plate antigen (BPA) agglutination tests and with two
      confirmatory tests, the 2-mercaptoethanol (2-ME) agglutination and the complement
      fixation (CF) tests. In the testing of Brucella abortus Strain 19 (S19)
      vaccinated cattle from Brucella-free dairy herds, the diagnostic specificity
      estimate of the ELISA (99.7%) was shown to be comparable to the RB (99.7%), 2-ME
      (99.8%) and CF (99.9%) and greater than the BPA (90.6%). In the testing of S19
      vaccinated cattle from infected herds, the sensitivity estimates of the BPA
      (99.5%, 99.6% and 98.6% respectively) relative to CF,2-ME and ELISA positive
      reactors were comparable and high. The relative sensitivity estimates of the RB
      (86.3%, 81.4% and 79.1%) in the same comparison were disparate and lower. The
      ELISA demonstrated the highest relative sensitivity estimates (97.1% and 95.2%
      respectively) in a three-way comparison between ELISA, CF and 2-ME positive
      reactors from these herds. Relative to BPA positive reactors from the same
      infected herds, the sensitivity estimate of the ELISA (57.0%) was comparable to
      the 2-ME (56.2%) and higher than the CF (51.8%). These results would suggest that
      the overall diagnostic specificity and sensitivity of the ELISA test is
      comparable, if not superior, to the tests used to confirm BPA positive reactor
      status.

PMID- 8533304
TI  - Immunophenotyping of canine bronchoalveolar and peripheral blood lymphocytes.
AB  - The immunophenotype of canine lymphocytes obtained by bronchoalveolar lavage
      (BAL) was investigated and compared with that of peripheral blood leukocytes
      (PBL). Indirect immunofluorescence, generated by monoclonal antibodies (mAb)
      specific for canine CD5, CD4, CD8, CD45pan, CD45RA, MHCII and THY-1, was detected
      by flow cytometry. In comparison with PBL, in BAL there are fewer lymphocytes
      positive for CD45RA (75.4 +/- 12.6% vs. 42.3 +/- 9.4%; P < 0.05) and MHCI I (97.0
      +/- 2.9% vs. 74.0 +/- 7.6%; P < 0.01), while there are more cells positive for
      CD8 (19.0 +/- 3.6% vs. 29.5 +/- 12.0%; P < 0.05). Thus there is a lower CD4/CD8
      ratio in the cell compartment accessible by BAL (2.2 +/- 0.3 vs. 1.3 +/- 0.6; P <
      0.005). The immunophenotype may be stable over time, as indicated by
      reexamination of cells obtained from one dog at four times over 1 year.
      Investigating the phenotype of lymphocytes from three different locations of the
      right lung, the cranial lobe lymphocytes show a lower CD4/CD8 ratio in comparison
      with PBL (1.81 +/- 0.35 vs. 1.12 +/- 0.31, n = 5; P < 0.02). In general, less
      MHCII positive lymphocytes (P < 0.001) and greater immunophenotype variability of
      results were found in these separate samples compared with pooled samples from
      these locations.

PMID- 8533305
TI  - Expression of gamma delta T cell receptor on caprine globule leukocytes.
AB  - Histochemical characteristics and immunological surface phenotypes of globule
      leukocytes (GLs) of normal goats were investigated in the intestine. In the small
      intestine, GLs were concentrated in the base of the villus and around the crypt,
      whereas in the cecum and colon they were randomly distributed. Their cytoplasmic
      granules exclusively stained with phosphotungstic acid hematoxylin, and were
      negative for peroxidase and histamine in contrast to those of subepithelial mast
      cells. The existence of chondroitin sulfate in some granules of GLs and heparin
      in most granules of mast cells were revealed by alcian blue staining and
      digestion with chondroitinase ABC. Isolated intestinal GLs were positive for T
      cell receptor (TcR) 1-N24 (gamma delta) and CD8 alpha, and negative for WC1-N3
      and WC1-N4. Cryostat sections of ileum revealed preferential intraepithelial
      distribution of both TcR1-N24+ cells and CD8+ cells. WC1-N3+ and WC1-N4+ cells
      were rarely seen in the epithelium and lamina propria. These results indicate
      that caprine GLs are a gamma delta T cell subset, which is a different cell
      population from WC1 positive gamma delta T cells.

PMID- 8533306
TI  - Analysis of feline dual lymphocyte populations observed by flow cytometry.
AB  - Two discrete lymphocyte populations were observed commonly on flow cytometric
      analysis (FCM) of feline lymphocyte subsets. The identity of these populations as
      small and large lymphocytes was established by correlating data from FCM with
      that from peripheral blood films. Dual lymphocyte populations were more likely to
      be seen in feline immunodeficiency virus-positive (FIV(-)+ ve) cats but their
      occurrence was not affected by health status, age, gender or breed. FIV(-)+ ve
      cats had a significantly higher proportion of large lymphocytes than FIV-negative
      (FIV(-)- ve) cats. However, FIV(-)+ ve cats had significantly fewer small
      lymphocytes than FIV(-)- ve cats but similar numbers of large lymphocytes.
      Lymphocyte subset analysis revealed that small lymphocytes had a greater
      proportion of CD4+ cells than large lymphocytes, regardless of the FIV or health
      status of the cat. In FIV(-)- ve cats, small lymphocytes had a greater proportion
      of Pan T + lymphocytes than large lymphocytes, but the converse was seen in FIV(
      )+ ve cats. The proportion of CD8 + cells was higher in small lymphocytes than
      large lymphocytes in well FIV(-)- ve cats but this distinction was not seen in
      sick FIV(-)- ve cats or FIV(-)+ ve cats of any health status. Regardless of
      health status, FIV(-)+ ve cats had a lower absolute count of small lymphocytes
      which were T cells (due to lower numbers of both CD4 + and CD8 + cells) than FIV(
      )- ve cats. The numbers of small B cells were similar for both FIV(-)+ ve and
      FIV(-)- ve cats. However, there were no differences between FIV(-)+ ve and FIV(-)
      ve cats in the absolute values of any subset of the large lymphocytes, which
      suggested that FIV may affect only small lymphocytes. Statistically, the
      inclusion or exclusion of the large lymphocyte population for routine lymphocyte
      subset analysis did not affect the overall results. However, because there were
      significant differences in subset distribution between small and large
      lymphocytes, analysis of both groups should be included in studies examining the
      role of lymphocytes in disease.

PMID- 8533307
TI  - Comparison of Freund's adjuvant and TiterMax in inducing anti-idiotype to
      idiotypic antibodies against pseudorabies virus antigens.
AB  - Freund's adjuvant (FA) and TiterMax (TM) were compared for their effectiveness in
      the induction of the anti-idiotypic antibodies (anti-Id or Ab2) in pigs, goats
      and mice against swine polyclonal anti-pseudorabies virus (PRV) antibodies (Ab1)
      by sequential immunization procedures. Both adjuvants had similar effects on
      inducing anti-swine immunoglobulin antibodies in the animals. However, high
      levels of the anti-Id were only generated in animals that received FA.
      Serological characterization of the anti-Id antisera indicated that internal
      image anti-Id (Ab2 beta) was generated that recognized shared idiotype (IdX) on
      the antibodies to PRV. The internal image Ab2 was capable of blocking the anti
      PRV antibodies from binding to the PRV antigens, and their interaction with anti
      PRV antibodies could be inhibited by PRV antigens.

PMID- 8533308
TI  - Comparison of adjuvants for immune potentiating properties and side effects in
      mice.
AB  - Four types of adjuvants were evaluated as alternatives to the use of Freund's
      complete adjuvant in mice. The adjuvants evaluated included a water-in-oil
      emulsion (Specol), a microorganism (Lactobacillus), performed immune-stimulating
      complexes (ISCOM) containing rabies virus glycoprotein and a saponin, Quil A. The
      adjuvants and saline were combined with three weak immunogens (a synthetic
      peptide, a self antigen and a particulate antigen) and given by three different
      routes (intraperitoneal, subcutaneous and dorsal in the foot). The evaluation was
      based on clinical observations, behavioural studies, pathological lesions and
      capacity to support immunological responses to weak immunogens. Lesions were most
      severe after injection of antigen combined with Freund's adjuvant or Quil A, mild
      to moderate with Specol and minimal with Lactobacillus, iscom conjugates or
      saline. Despite pathological changes, no signs of prolonged pain or distress
      could be demonstrated based on clinical observations and behavioural studies.
      Minimal immunological responses were found after injection of antigen in
      combination with saline or Lactobacillus. T-cell activation and high antibody
      responses were found after injection of antigen-iscom conjugates or antigen in
      Freund's adjuvant emulsions. After Specol/antigen immunisations T-cell activation
      was demonstrated and high antibody titres were found except for Specol/self
      antigen immunisations. Presented data suggest that Specol is a possible
      alternative to Freund's complete adjuvant for the induction of an immune response
      against weak immunogens except possibly self antigens, for which performed iscoms
      seem very suitable.

PMID- 8533309
TI  - An assessment of mucosal immunisation in protection against Streptococcus equi
      ('Strangles') infections in horses.
AB  - The ability of mucosally administered antigen to provide protection against
      Streptococcus equi ('Strangles') infections in horses was examined. First, an
      enzyme linked immunosorbent assay (ELISA) was developed to detect the immune
      status of horses to S. equi. This assay was used to select Strangles-naive horses
      for the study and also to monitor their response to immunisation. Potential
      vaccine candidates were: (a) orally administered paraformaldehyde killed S. equi;
      (b) intraperitoneally (IP) administered paraformaldehyde killed S. equi in a non
      inflammatory adjuvant; (c) orally administered live avirulent S. equi; (d) orally
      administered microencapsulated streptococcal M protein. The latter three
      preparations were first assessed in a rat model, using rate of lung bacterial
      clearance following intratracheal inoculation of live virulent bacteria as an
      indication of efficacy. Candidates (a) and (b) were then assessed in an equine
      model. IP immunisation of horses was shown to effectively induce production of
      specific antibody in mucosal and systemic sites. Four weeks after initial
      immunisation, horses were challenged intranasally with live virulent S. equi.
      Both groups of immunised horses demonstrated partial protection following
      vaccination. Of the IP immunised horses, only two out of four developed clinical
      signs of Strangles following live challenge. The orally immunised horses all
      developed submandibular abscesses containing S. equi. However, none of the
      immunised horses became as ill as the control horses in terms of fever, anorexia,
      loss of condition and general malaise.

PMID- 8533310
TI  - Differences in distribution of lymphocyte antigens in chicken lines divergently
      selected for antibody responses to sheep red blood cells.
AB  - The proportion of cells showing differentiation antigens specific for T cells, B
      cells and leukocytes was studied at various ages in peripheral blood, and at 14
      weeks of age in the bursa of Fabricius, spleen and thymus of two lines of chicken
      that had been selected over 13 generations for either high (H) or low (L)
      antibody responses to sheep red blood cells (SRBC), and also in a randombred
      control (C) line. Flow cytometry showed no consistently significant differences
      between the three lines in numbers of circulating lymphocytes and other
      leukocytes after hatching. However, higher percentages of CD4+ cells and B cells
      were present in the spleen and thymus from the H line compared with the L line.
      However, the L line was characterized by a higher proportion of splenic CD8+
      cells and spleen cells expressing gamma-delta T-cell receptors. Immunization with
      sheep red blood cells had no effect on the distribution of CD4+ or CD8+ cells in
      the various tissues at 2 and 7 days after immunization. These results suggest
      that previously reported differences in in vivo immune responses between these
      chicken lines may be related to the differences in resident T-lymphocyte
      subpopulations in the lymphoid tissues. The involvement of T-cell subsets and non
      antigen-specific mechanisms in divergent selection on humoral immune responses in
      chickens is discussed.

PMID- 8533311
TI  - Studies on the haemolytic complement of the dromedary camel (Camelus
      dromedarius). II. Alternate complement pathway haemolytic activity in serum.
AB  - Fresh camel serum caused lysis of unsensitised red blood cells (RBC) of chicken,
      rabbit and guinea pig. Homologous RBC were resistant to lysis. There was only
      minimal lysis of goat, sheep, rat and cattle RBC. Lysis of heterologous RBC was
      attributed to the presence of alternate complement activity (ACP) in the serum as
      adsorption with respective RBC and addition of 10 mM ethylene glycol
      bistetraacetate (EGTA) in the SVBS diluent did not abrogate the haemolytic
      activity. Guinea pig RBC were the most sensitive to lysis, giving a mean ACP
      activity of 41.5 +/- 1.8 CH50 units ml-1. Clotting, followed by storing of blood
      between 0 and 37 degrees C for 1 h did not significantly affect ACP activity.
      However, considerable activity was lost when blood was clotted and stored at 44
      degrees C for 1 h, or when serum was kept at 4 degrees C for 24 h. Treatment with
      zymosan, or incubation at 56 degrees C for 30 min inhibited ACP activity. Maximum
      ACP activity occurred in the presence of 8 mM Mg2+ in the SVBS-EGTA diluent, at
      pH 7.3 and incubation time of 2 h at 37 degrees C. Levels of ACP activity were
      determined in 79 healthy camels of different age groups, ranging from 3 months to
      15 years. Calves between 3 months and 1 year of age had higher ACP activity than
      camels in the age group of 5 years and above. Highest mean ACP activity of 89 +/-
      7.9 CH50 units ml-1 were recorded in 1-5 year old camels (P < 0.0001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8533312
TI  - Demonstration of serum antiplatelet antibodies in experimental acute canine
      ehrlichiosis.
AB  - This report presents evidence for the presence of antiplatelet antibodies in sera
      of dogs experimentally infected with Ehrlichia canis, during the acute phase of
      the disease. Six healthy adult male beagle dogs were inoculated intravenously
      with blood from a longstanding infected dog with the Israel strain 611 of E.
      canis. Thrombocytopenia and concurrent increase in mean platelet volume were the
      most consistent haematological signs of the disease. The dogs developed an
      antibody titre to E. canis from Day 15 postinoculation. All dogs were
      antiplatelet antibody negative before inoculation. Twenty-four days
      postinoculation with E. canis, when the platelet count was at its lowest,
      antibodies to platelets were demonstrated, in the sera of five of the six dogs.

PMID- 8533313
TI  - Responses of bovine T cells to fractionated lysate and culture filtrate proteins
      of Mycobacterium bovis BCG.
AB  - Bacterial cell lysates and culture filtrate proteins of Mycobacterium bovis BCG
      were each separated in a two-dimensional system that yields soluble protein
      fractions immediately available for probing with T cells. The fractions were used
      in lymphocyte proliferation assays using blood lymphocytes from cattle immunized
      with either viable or gamma-irradiated BCG. Cattle immunized with either form of
      BCG responded similarly to fractionated lysate proteins. Cattle immunized with
      viable BCG responded to culture filtrate proteins that were not recognized by
      cattle immunized with dead BCG. Marked heterogeneity of the responses to the
      culture filtrate proteins was seen.

PMID- 8533314
TI  - Bioactivity of recombinant feline interleukin-2 on human and feline leukocytes.
AB  - Interleukin (IL)-2 is a 16,000 Da protein product of T lymphocytes which is the
      principle cytokine responsible for clonal expansion of T lymphocytes as a
      response to antigen exposure. Deficiency of functional IL-2 plays a pivotal role
      in the pathogenesis of human immunodeficiency syndrome and may be important in
      the pathogenesis of feline immunodeficiency syndrome as well. Additionally, IL-2
      may enhance secretion of interleukin-5 from the TH2 subset of CD4+ T cells,
      promote peripheral and systemic eosinophilia, and contribute to the eosinophilia
      which characterizes the inflamed airways of human beings and cats with asthma. We
      recently reported the sequence of feline IL-2 and the synthesis of recombinant
      feline IL-2. The purpose of the present study was to evaluate the bioactivity of
      recombinant feline IL-2 on human and feline leukocytes. We established dose
      response relationships between recombinant feline IL-2 and radiolabeled
      proliferating human and feline leukocytes using thymidine incorporation as a
      marker of bioactivity. We found that recombinant human IL-2 promotes
      proliferation of both human and feline leukocytes. However, recombinant feline IL
      2 promotes proliferation of feline cells, but not human cells.

PMID- 8533315
TI  - Cellular immune responses of pigs after primary inoculation with porcine
      respiratory coronavirus or transmissible gastroenteritis virus and challenge with
      transmissible gastroenteritis virus.
AB  - The contribution of cell-mediated immunity to protective immunity against
      virulent transmissible gastroenteritis virus (TGEV) infection conferred by
      primary porcine respiratory coronavirus (PRCV) or TGEV exposure was assessed in
      pigs that were challenged with TGEV 24 days after a primary oronasal inoculation
      with PRCV or TGEV when 11 days old. PRCV exposure induced partial protection
      against TGEV challenge in suckling pigs based upon a decreased number of diarrhea
      cases (42% vs. 90% in age-matched control pigs), limited virus shedding in feces,
      and increases in virus-neutralizing serum antibody titers; in contrast, all 11
      day-old pigs inoculated with TGEV were completely protected after challenge.
      Weaned pigs were also studied to eliminate any possibility that lactogenic
      immunity from contact PRCV-exposed sows contributed to protection against TGEV.
      Once weaned, none of the PRCV-exposed or age-matched control pigs had diarrhea
      after TGEV challenge; moreover, both groups exhibited less rectal virus shedding
      than suckling pigs. Vigorous lymphocyte proliferative responses (> 96,000 counts
      per minute (cpm)) were detected in mononuclear cells prepared from mesenteric
      (MLN) and bronchial (BLN) lymph nodes of TGEV-primed pigs. Analyses of these
      responses indicate that virus-specific cell-mediated immune responses correlated
      with protection against rectal and nasal virus shedding after TGEV challenge.
      Primary inoculation of 11-day-old pigs with PRCV induced moderate, transient
      virus-specific lymphocyte proliferation (> 47,000 cpm) in MLN from both suckling
      and weaned pigs after TGEV challenge. Substantial BLN proliferative responses (>
      80,000 cpm) correlated with failure to detect TGEV in nasal secretions from these
      pigs. Virus-specific lymphocyte proliferation in spleens was delayed in onset and
      of lower magnitude than that observed in MLN and BLN. Virulent TGEV exposure
      resulted in increased percentages of T cell subsets, especially in the lamina
      propria and MLN, mucosa-associated lymphoid tissues in proximity to the primary
      replication site of TGEV in the small intestine. Our results confirm that PRCV
      infection primes anti-viral immune responses and, thus, contributes to partial
      immunity against virulent TGEV challenge.

PMID- 8533316
TI  - Allograft rejection in cattle with bovine leukocyte adhesion deficiency.
AB  - In the present investigation cell-mediated immunity in animals with bovine
      leukocyte adhesion deficiency (BLAD) was studied by means of skin transplantation
      experiments. Autograft and allograft behaviour in animals with BLAD was compared
      with the behaviour of simultaneously transplanted autografts and allografts in
      healthy controls. Allograft survival time was prolonged in three BLAD cattle (28,
      30, and 72 days) compared to six healthy controls (12-14 days). When
      transplantations were repeated on one animal with BLAD using skin grafts from the
      same donor, accelerated rejection was observed (allograft survival time decreased
      from 72 days at primary to 35 days at secondary and to 21 days at tertiary
      transplantation), suggesting the development of immunological memory. Graft
      infiltrating lymphocytes that were obtained from allograft biopsies during the
      period of rejection, were shown to be from recipient origin (beta 2-integrin
      negative). Our findings demonstrate that, although prolonged allograft survival
      is observed in cattle with BLAD, skin allografts are ultimately rejected.

PMID- 8533317
TI  - Up-regulation of IL-2 receptor alpha and MHC class II expression on lymphocyte
      subpopulations from bovine leukemia virus infected lymphocytotic cows.
AB  - Infection with bovine leukemia virus (BLV) leads to a persistent lymphocytosis
      (PL) characterized by a marked increase in circulating B lymphocytes that express
      the orthologue of CD5. To gain insight into the factors accounting for
      lymphocytosis, experiments were conducted to determine the functional activation
      status of lymphocytes from BLV seronegative and BLV infected aleukemic cows with
      PL. Stimulation with the B lymphocyte mitogen Staphylococcus aureus Cowan strain
      I (SAC), recombinant human interleukin-2 (rIL-2), or pokeweed mitogen (PWM), a T
      lymphocyte-dependent B lymphocyte mitogen, revealed differences in the pattern of
      expression of IL-2 receptor alpha (IL-2R alpha) and major histocompatibility
      (MHC) class II molecules on B and T lymphocytes from uninfected and BLV infected
      PL cows. rIL-2 induced expression of IL-R alpha on B lymphocytes from PL cows but
      not B lymphocytes from BLV seronegative cows. SAC alone, or in combination with
      rIL-2, had no effect on B lymphocytes from BLV seronegative cows. However, rIL-2
      alone or in combination with SAC induced expression of IL-2R alpha on B
      lymphocytes from PL cows. PWM stimulated expression of IL-2R alpha on bovine B
      lymphocytes regardless of BLV status, and induced a significantly higher level of
      expression on B lymphocytes from PL cows. Mitogens and rIL-2 had a similar
      stimulatory effect on induction of IL-2R alpha expression on CD4 T lymphocytes
      regardless of BLV status. Only PWM induced expression of IL-2R alpha on bovine
      CD8 T lymphocytes and induced a significantly higher level of expression on this
      T lymphocyte subset from PL cows. Examination of freshly isolated B lymphocytes
      from PL cows revealed increased spontaneous expression of the MHC class II
      molecule compared to B lymphocytes from control cows. None of the culture
      conditions examined induced MHC-II expression on CD4 and CD8 T lymphocytes from
      BLV seronegative cows. In contrast, SAC+IL-2 and PWM induced MHC-II expression on
      CD4 and CD8 T lymphocytes from BLV infected PL cows, resulting in a significantly
      greater proportions of these lymphocyte subsets expressing this molecule compared
      to CD4 and CD8 T lymphocytes from control cows. The data indicate that infection
      with BLV affects the response of B and T lymphocytes to signals of activation, up
      regulating the expression of surface molecules involved in both direct contact
      and cytokine-mediated T lymphocyte-dependent B lymphocyte activation.

PMID- 8533318
TI  - Effect of bovine leukemia virus infection on bovine peripheral blood monocyte
      responsiveness to lipopolysaccharide stimulation in vitro.
AB  - The effects of bovine leukemia virus (BLV) infection on cytokine activity of
      bovine monocytes stimulated with Escherichia coli lipopolysaccharide (LPS) were
      examined. Compared to supernatants of LPS-stimulated monocytes from BLV-negative
      cows, supernatants from BLV-positive cows contained about four times more
      interleukin-1 beta (IL-1 beta) (as measured by an enzyme-linked immunosorbent
      assay (ELISA) for bovine IL-1 beta). Despite their higher IL-1 beta
      concentration, supernatants from BLV-positive cows stimulated proliferation of
      murine thymocytes in the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-biphenyl
      tetrazolium bromide) assay similar to supernatants from BLV-negative cows, but
      showed about 30% less IL-1 activity than supernatants from BLV-negative cows on
      the IL-1-dependent cell line LBRM-33 1 A-5, and about five times more tumor
      necrosis factor (TNF) activity on the TNF-sensitive murine fibroblast cell line L
      929. These results demonstrate that BLV infection changes the cytokine response
      of bovine monocytes to LPS stimulation in vitro. The results are consistent with
      the assumption that BLV infection leads to the production and secretion of a
      soluble IL-1 inhibitor by LPS-stimulated peripheral blood monocytes.

PMID- 8533319
TI  - The heterogeneity of bovine IgG2. VII. The phenotypic distribution of the A1 and
      A2 allotypes of IgG2a among beef cows with known clinical history.
AB  - A1 and A2 are allotypes of bovine IgG2a which differ significantly in their
      primary structure, allotope expression and the products of pepsin digestion. An
      analysis of 754 beef cows from 14 different breeds at the Meat Animal Research
      Center (MARC), Clay Center, NE, demonstrated a significant difference in the
      distribution of A1 and A2 among breeds but failed to find any correlation between
      the clinical disease history of the animals tested and their A-allotype. The
      proportion of all animals with either a history of infectious or respiratory
      disease (43.3 +/- 3.5 and 17 +/- 0, respectively) was the same among A1/A1, A1/A2
      and A2/A2 animals. Similarly, there was no preferential association between
      allotype and clinical disease within any one breed. A very high incidence of A1
      homozygotes was found among Angus (84%), Brown Swiss (100%), Limousin (87%), MARC
      I (87%) and Pinzgauers (88%). In contrast, Herefords had a high incidence of
      A2/A2 homozygotes (41%) as did Brahmans (46%) and Gelbveih (34%). The
      distribution of A1/A1, A1/A2 and A2/A2 animals within any breed was totally
      consistent with the concept that A1 and A2 represent Mendelian co-dominant
      alleles. These data suggest that, among vaccinated female beef cattle in a normal
      environment, A-allotypy plays no role in the propensity for clinical disease as
      defined in this study. It does not rule out such an association in non
      vaccinated, severely stressed animals and in calves exposed to severe outbreaks
      of an infectious agent.

PMID- 8533320
TI  - Immune responsiveness of Romney sheep selected for resistance or susceptibility
      to gastrointestinal nematodes: field studies.
AB  - Long-term selection of sheep for resistance to parasite infections may be
      jeopardized if animals do not retain their normal ability to respond to non
      parasite antigens. Therefore the antibody responses to ovalbumin (OVA) and human
      red blood cells (HRBC), and kinetics of peripheral blood lymphocyte phenotypes
      were examined in mature grazing sheep, genetically resistant or susceptible to
      gastrointestinal nematodes. In both lines the HRBC antibody response peaked 2
      weeks after the primary injection, 1 week after the second injection and 3 weeks
      after the second OVA injection. The antibody titres of the resistant line sheep
      decreased sooner after both primary and secondary injections. The resistant line
      sheep had higher percentages of CD5+ and CD4+ cells than the susceptible sheep.
      Two injections of OVA and HRBC did not result in significant alterations in
      percentages of CD5+, CD4+, CD8+ and CD45R+ lymphocytes in either line. In both
      lines, the control groups showed a steady increase of 0.29% per week in
      percentages of T19+ (gamma delta) T cells which was significantly higher than in
      the antigen injected sheep.

PMID- 8533321
TI  - Phototransduction in human cones measured using the alpha-wave of the ERG.
AB  - To study human cone phototransduction, the alpha-wave of the ERG was recorded
      from color normals, dichromats, and patients with retinitis pigmentosa. A model
      of the activation phase of phototransduction, previously fitted to responses from
      single rods and the rod alpha-wave, was modified and fitted to the human cone
      alpha-wave. The modified model fits the cone alpha-wave well and allows questions
      about human cone phototransduction to be addressed. In particular, we conclude
      that: (1) the amplification of the activation phase of human cone transduction is
      comparable to that of the human rods. (2) Steady lights have relatively little
      effect on the amplification of cone transduction. (3) The normal alpha-wave
      elicited by red flashes is dominated by the L cones, consistent with a ratio of
      L:M cones of > 1. (4) Retinitis pigmentosa caused by mutations of the rhodopsin
      gene can affect cone phototransduction. Finally, a simpler computational
      expression is shown to approximate the modified model's responses.

PMID- 8533322
TI  - Combining speed information across space.
AB  - We used speed discrimination tasks to measure the ability of observers to combine
      speed information from multiple stimuli distributed across space. We compared
      speed discrimination thresholds in a classical discrimination paradigm to those
      in an uncertainty/search paradigm. Thresholds were measured using a temporal two
      interval forced-choice design. In the discrimination paradigm, the n gratings in
      each interval all moved at the same speed and observers were asked to choose the
      interval with the faster gratings. Discrimination thresholds for this paradigm
      decreased as the number of gratings increased. This decrease was not due to
      increasing the effective stimulus area as a control experiment that increased the
      area of a single grating did not show a similar improvement in thresholds. Adding
      independent speed noise to each of the n gratings caused thresholds to decrease
      at a rate similar to the original no-noise case, consistent with observers
      combining an independent sample of speed from each grating in both the added- and
      no-noise cases. In the search paradigm, observers were asked to choose the
      interval in which one of the n gratings moved faster. Thresholds in this case
      increased with the number of gratings, behavior traditionally attributed to an
      input bottleneck. However, results from the discrimination paradigm showed that
      the increase was not due to observers' inability to process these gratings. We
      have also shown that the opposite trends of the data in the two paradigms can be
      predicted by a decision theory model that combines independent samples of speed
      information across space. This demonstrates that models typically used in
      classical detection and discrimination paradigms are also applicable to search
      paradigms. As our model does not distinguish between samples in space and time,
      it predicts that discrimination performance should be the same regardless of
      whether the gratings are presented in two spatial intervals or two temporal
      intervals. Our last experiment largely confirmed this prediction.

PMID- 8533323
TI  - Investigating simple and complex mechanisms in texture segregation using the
      speed-accuracy tradeoff method.
AB  - Several recent models of texture segregation have proposed two mechanisms:
      simple, linear channels (first-order, Fourier mechanisms) and complex channels
      (second-order, non-Fourier mechanisms). We used the speed-accuracy tradeoff (SAT)
      method to examine the time course of texture segregation processing in simple and
      complex channels. The stimuli were texture patterns designed to segregate
      primarily as a result of activity in one set of channels or the other. We
      presented subjects with textures that were checked or striped arrangements of
      either Gaussian-blob or Gabor-patch elements. Subjects were required to identify
      the orientation of a rectangular texture region embedded in a background field of
      a different texture. A range of contrasts and a control task were used to equate
      visibility of the Gabor and Gaussian textures. SAT functions were obtained by
      requiring subjects to respond within 200 msec after an auditory cue. We found
      that when segregation depended primarily on simple channels, performance was
      faster than when it depended primarily on complex channels: the 75% correct level
      was reached 100-200 msec sooner and this extra speed was reflected both in
      smaller delay and higher rate parameters.

PMID- 8533324
TI  - Depth release of illusory contour shape in the Ehrenstein grid.
AB  - In the Ehrenstein grid, bright illusory patches delineated by illusory contours
      are seen. In order to assess whether the illusory patches possess shape
      constancy, the Ehrenstein grid was viewed straight on and at various angles of
      slant with respect to the observer. Observers matched the apparent shape of the
      illusory patches with a circle or an ellipse defined by real lines in a reference
      stimulus. Results show that, when viewed at a slanted angle, the shape of the
      bright patches was deformed and became oval. Such deformation was much less when
      the illusory contours were replaced by real contours. We label this dissociation
      of shape perception from depth cues depth release to contrast it with the
      previously described phenomenon of depth capture in which depth cues displace the
      illusory patches in depth. As a common explanation for both effects, it is
      proposed that the illusory contours induced by line ends or line ends themselves
      provide only weak or ineffective depth signals.

PMID- 8533325
TI  - Propagation of local motion correspondence.
AB  - We examined how the direction of apparent motion in one part of a scene can
      propagate and constrain motion direction in another part. The stimulus scene
      consisted of an array of dots all moving in the same physical direction at the
      same time. According to the proximity rule, the dots in the interior of the array
      should appear to move rightward and the dots at the edges should appear to
      oscillate horizontally. However, we found that: (1) with long frame durations,
      the interior dots also appeared to oscillate; (2) with shorter frame durations,
      the likelihood that the subjects perceived rightward motion at the center of the
      array increased; (3) oscillation was observed at the edges regardless of frame
      duration; (4) when opaque objects were placed on both the left and right sides of
      the array as occluders, only rightward motion was observed both in the center and
      at the edges of the occluders independent of frame duration; (5) in all cases,
      similar results were obtained with both foveal and peripheral viewing of either
      the center or the edge; and (6) with longer frame durations, the interior area
      within which oscillations were observed became larger. These findings suggest
      that signals for motion correspondence (oscillation) can gradually propagate to
      distant units (roughly 30 deg/sec). This can be explained by a locally-connected
      iterative network model.

PMID- 8533326
TI  - Discrimination of orientation-defined texture edges.
AB  - Preattentive texture segregation was examined using textures composed of randomly
      placed, oriented line segments. A difference in texture element orientation
      produced an illusory, or orientation-defined, texture edge. Subjects
      discriminated between two textures, one with a straight texture edge and one with
      a "wavy" texture edge. Across conditions the orientation of the texture elements
      and the orientation of the texture edge varied. Although the orientation
      difference across the texture edge (the "texture gradient") is an important
      determinant of texture segregation performance, it is not the only one. Evidence
      from several experiments suggests that configural effects are also important.
      That is, orientation-defined texture edges are strongest when the texture
      elements (on one side of the edge) are parallel to the edge. This result is not
      consistent with a number of texture segregation models including feature- and
      filter-based models. One possible explanation is that the second-order channel
      used to detect a texture edge of a particular orientation gives greater weight to
      first-order input channels of that same orientation.

PMID- 8533327
TI  - Speed gradients and the perception of surface slant: analysis is two-dimensional
      not one-dimensional.
AB  - Motion parallax provides cues to the three-dimensional layout of a viewed scene
      and, in particular, to surface tilt and slant. For example, as a textured
      surface, inclined around a horizontal axis, translates horizontally relative to
      an observer's view point, then, in the absence of head and eye movements, the
      observer's retinal flow will contain a one-dimensional (1D) vertical speed
      gradient. The direction of this gradient indicates the direction of surface tilt,
      and its magnitude and sign can be used in calculating the magnitude and sign of
      the surface slant. Alternatively, the same retinal flow contains a 1D translating
      component, plus a two-dimensional (2D) component of rotation (curl), and a 2D
      component of deformation (def). On this view, the direction of surface tilt is
      related to the orientation of def and the magnitude and sign of the surface slant
      is related to the magnitude and sign of def. We used computer generated random
      dot patterns as stimuli to determine whether the human visual system employs a 1D
      analysis (i.e. 1D speed gradients) or a 2D analysis (i.e. deformation) of surface
      slant from motion parallax. Using a matching technique we found compelling
      impressions of slant when we vector summed a translation field with (i) vertical
      shear, horizontal shear or deformation (made from vertical and horizontal shear),
      but not rotation; and (ii) vertical compression, horizontal compression or
      deformation (made from vertical and horizontal compression), but much less so for
      expansion. In both cases, the first three conditions contain def, but the fourth
      does not, and the last three conditions contain 1D speed gradients orthogonal to
      the perceived axis of inclination, but the first one does not. Therefore, the
      results from the first and fourth conditions distinguish between the two
      processing strategies. They support the idea that surface slant is coded by
      combining both horizontal and vertical speed gradients in a way similar to the 2D
      differential invariant def and oppose the view that surface slant is encoded by a
      1D analysis of motion in a direction orthogonal to the perceived axis of
      inclination. In a further experiment, we found essentially no effect of reducing
      the field size from 18 to 9 deg.

PMID- 8533329
TI  - Perceptual consequences of ocular lens overshoot during saccadic eye movements.
AB  - In a previous paper we compared eye globe records of saccadic eye movements
      (recorded with a scleral eye coil) with lens reflection records of the same eye
      movements (recorded with a dual-Purkinje-image eyetracker); we found evidence for
      considerable dynamic deviations between the two during and immediately after
      saccades. We ascribed these deviations to the movements of the eye's lens
      relative to the optical axis of the eye. This paper quantifies a predicted
      psychophysical effect of lens displacements during and after saccades. Two small
      targets, one above the other, were flashed for 2 msec in total darkness, the
      bottom one exactly at the end of the saccade, the top one 30 msec later. The
      first target appears deviated horizontally relative to the other, in a direction
      opposite to the saccade. Magnitude of the relative mislocalization can be up to
      0.03 deg for each degree of saccadic eye movement. The result shows that the
      position of the visual image on the retina is affected both by position of the
      globe and by deviations of the lens from its normal location.

PMID- 8533328
TI  - Disambiguating velocity estimates across image space.
AB  - A translating homogeneous edge viewed through an aperture is an ambiguous
      stimulus, while a translating edge discontinuity is unambiguous. Under what
      conditions does the visual system use unambiguous velocity estimates to interpret
      ambiguous velocity estimates? We considered a translating rectangle visible
      through a set of stationary apertures. One aperture displayed a rectangle edge
      while the other apertures displayed corners. Observers reported the direction in
      which the edge appeared to translate. The results suggest that collinearity and
      terminator proximity determine whether the unambiguous corner velocity was used
      to interpret the ambiguous edge velocity. These results suggest some of the ways
      in which the visual system controls the integration of velocity estimates across
      image space.

PMID- 8533330
TI  - Optokinetic nystagmus (OKN) suppression by fixation of a stabilized target: the
      effect of OKN-stimulus predictability.
AB  - In previous work, subjects looked at a target stabilized at the fovea,
      superimposed on a sinusiodally moving OKN stimulus. The stabilized target (no
      retinal-slip) suppressed OKN leaving residual eye movements that were often in
      counterphase with the OKN stimulus motion. In the present study we explored how
      this type of suppression of OKN is influenced by OKN stimulus predictability: OKN
      stimulus motion was either sinusoidal or a random walk of half-sinusoids. During
      fixation of a stabilized target with sinusoidal stimulus motion, OKN was
      suppressed leaving residual eye movement whose amplitude was typically less than
      OKN and with a phase lag of about 180 deg (roughly in counterphase with stimulus
      motion). With random-walk stimulus motion, the residual movement amplitude was
      even smaller, and at higher frequencies the phase lag decreased to become the
      same as for OKN. For both stimulus motions, OKN was suppressed when the target
      was present, but counterphase residual movements appear to depend on stimulus
      predictability.

PMID- 8533331
TI  - Saccadic reaction times in gap/overlap paradigms: a model based on integration of
      intentional and visual information on neural, dynamic fields.
AB  - The systematic variations of regular saccadic reaction times induced in
      gap/overlap paradigms are addressed by a quantitative model. Intentional and
      visual information are integrated on a retinotopic representation of visual
      space, on which activity dynamics is related to movement initiation. Using a
      specific conception of "motor preparation", known effects of general warnings and
      fixation point on- and offsets are reproduced. Results of new experiments are
      predicted and the extent to which fixation point offsets are specific to ocular
      responses is analyzed in the light of the exposed model architecture. Relations
      of the theoretical framework to neurophysiological findings are discussed.

PMID- 8533332
TI  - Two-dimensional constraints on three-dimensional structure from motion tasks.
AB  - Can humans recover metric structure from motion sequences or, as has been claimed
      by Todd and Bressan [(1990) Perception & Psychophysics, 48, 419-430], are they
      limited to recovering only relief structure? Two experiments were carried out to
      investigate this question. In a metric-structure task, the angular thresholds for
      discriminating two rotating bi-planar structures were approximately 91 deg. By
      contrast, in a relief-structure task, the angular thresholds for discriminating a
      planar from a non-planar structure, both undergoing simple rotational motion,
      were only approximately 11 deg. A computational model is proposed to examine the
      image motion sensitivity required to perform discriminations of both three
      dimensional metric and relief structure from motion. When the experimental data
      were re-plotted in terms of this two-dimensional sensitivity, the thresholds were
      found to be the same for both tasks. This finding is related to the model's
      revelation that recovering metric structure from motion is inherently more noise
      sensitive than is recovering relief structure from motion. The conclusion is that
      the differences in angular thresholds reflect the differing nature of the two
      tasks. There is no evidence that the visual processes themselves are
      preferentially sensitive to non-metric over metric structure from motion.

PMID- 8533333
TI  - Effects of flicker adaptation and temporal gain control on the flicker ERG.
AB  - The flicker electroretinogram (ERG) to stimuli varying in temporal frequency and
      modulation depth was recorded to investigate retinal gain control. With
      increasing modulation of a sinusoidal flickering stimulus, the flicker ERG shows
      an amplitude compression and a phase retardation (of the fundamental component)
      at 16 Hz, an amplitude expansion and a phase advance around 40-48 Hz, and an
      approximately linear response at 72 Hz. With sum-of-two-sinusoids stimuli, the
      second stimulus enhances the fundamental response to a 40 or 48 Hz test stimulus
      at low modulations, and reduces the variation in phase with modulation. This
      interaction depends primarily on the amplitude of the response to the second
      stimulus, but not its frequency. With temporally alternating stimuli, a similar
      but smaller interaction effect is measured. The results suggest that there is an
      active nonlinear gain control mechanism in the outer retina and this gain control
      works by adjusting the phase delay of the retinal response. The phase control
      mechanism is set by the amplitude of the outer retinal response integrated over
      time.

PMID- 8533334
TI  - Human efficiency for recognizing and detecting low-pass filtered objects.
AB  - Recently, Tjan, Braje, Legge and Kersten [(1995) Vision Research, 35, 3053-3069]
      found that human efficiency for object recognition was less than 10%, indicating
      that humans fail to use much of the information available to an ideal observer.
      We examine two explanations for these low efficiencies: (1) humans are
      inefficient in using high spatial-frequency information; and (2) humans are
      inefficient in detecting image samples. We tested the first possibility by
      measuring human efficiency for recognizing low-pass filtered objects, rendered as
      line drawings and silhouettes, in luminance noise. Efficiency did not improve
      when high frequencies were removed, and the first explanation was rejected. We
      tested the second explanation by comparing efficiencies for object detection and
      recognition. Recognition efficiency was higher than detection efficiency for
      silhouettes but not line drawings, showing that detection efficiency does not
      place a ceiling on recognition efficiency. The results indicate that human vision
      is designed to extract image features, such as contours, that enhance
      recognition. A computer simulation suggests that this can occur if the observer
      views the world through a band-pass spatial-frequency channel.

PMID- 8533335
TI  - The prediction of hue and saturation for non-spectral lights.
AB  - The Jameson and Hurvich opponent-colors model of hue and saturation was tested
      for spectral and non-spectral lights. Four observers described the color of
      lights by scaling hue and saturation. The lights ranged from 440 to 640 nm and
      consisted of five purities: 1.0, 0.80, 0.60, 0.40 and 0.20. Admixtures of
      monochromatic and a xenon-white light yielded the different colorimetric
      purities. For each subject, chromatic response functions were measured by the
      method of hue cancellation at each purity, and an achromatic response function
      was measured by the method of heterochromatic flicker photometry for spectral
      lights. Chromatic response functions measured for a particular purity and the
      achromatic response function were used to predict hue and saturation for that
      purity. The model successfully predicted hue at each level of purity, but failed
      to predict precisely the Abney effect. The model made relatively poor predictions
      of saturation, tending to overestimate short-wave lights and underestimate long
      wave lights. An additional experiment found that stimulus parameters that favor
      rod contribution weaken the model's predictions of saturation, while stimulus
      parameters that do not favor rod contribution improve the model's predictions of
      saturation.

PMID- 8533336
TI  - Shape from shaded random surfaces.
AB  - The perception of surface relief from random shading patterns is measured by
      having observers adjust three-dimensional local probes, the projections of which
      are superimposed on the image. Three observers perform four settings of 91 probes
      on each of 14 images. These images are generated by calculating the Lambertian
      reflectance of a random superposition of elliptical Gaussian hills and valleys
      illuminated by a single distant light source as well as by ambient light. Neither
      the surface reflectance equation nor the light source direction is conveyed to
      our observers in any way. Mathematically, this "pure" shape-from-shading problem
      has highly non-unique solutions. Perception of a well-defined, stable shape
      therefore implies that the ambiguity is resolved, i.e. a gauge is fixed. We
      analyse the surface ambiguity or gauge freedom which is left unconstrained by
      pure shading information and we investigate possible ways of restricting it.
      Statistical analysis of the curl component of the field of probe settings reveals
      that the settings are significantly consistent with an underlying perceived
      surface. In spite of the large theoretical ambiguity in the stimuli, the settings
      are reproducible and show considerable inter-observer agreement. Even the
      correlation of the settings with the real surfaces is surprisingly large. If the
      settings are compared to the real surface normals, one finds a series of biases,
      the strongest of which is that the global surface slant is systematically
      underestimated, even in those cases where ending occluding contours or high
      contrast luminance ridges, indicative of "almost" contours, are present in the
      image. Another bias then is that the corresponding rims on the surface are seen
      as roughly parallel to the picture plane.

PMID- 8533337
TI  - Fast perceptual learning in hyperacuity.
AB  - We investigated fast improvement of visual performance in several hyperacuity
      tasks such as vernier acuity and stereoscopic depth perception in almost 100
      observers. Results indicate that the fast phase of perceptual learning, occurring
      within less than 1 hr of training, is specific for the visual field position and
      for the particular hyperacuity task, but is only partly specific for the eye
      trained and for the offset tested. Learning occurs without feedback. We
      conjecture that the site of learning may be quite early in the visual pathway.

PMID- 8533338
TI  - The spatiotemporal range of inhibitory interaction in flicker detection.
AB  - The flicker thresholds of luminous bars were measured as a function of the
      spatial and/or temporal separation of two flickering stimuli. Each of the bars
      had an intensity profile of one-half cycle of a sinusoidal wave subtending 2.26 x
      0.45 arc deg and each bar was presented twice at two positions with a duration of
      10 msec. The spatial separation was defined as the distance between the adjacent
      flanks of two flickering stimuli, while the temporal separation was determined as
      the time-lag between the offset of the first flickering stimulus and the onset of
      the second. We found that the thresholds increased asymptotically with the
      spatial separation in such a way as to suggest that the spatial extent over which
      inhibitory interaction could be effective was as large as about 2 arc deg. We
      also found that the threshold gradually decreased with greater temporal
      separation; this indicated that the temporal proximity of successive stimuli
      effects less suppression on the temporal response. These two effects were
      seemingly additive. These findings suggest that the visual system involves not
      only local spatial interaction, but also a global mechanism capable of spreading
      inhibition over several local units after a delay of several msec.

PMID- 8533339
TI  - Visual mislocalization produced by a rapid image displacement on the retina:
      examination by means of dichoptic presentation of a target and its background
      scene.
AB  - The time course of visual mislocalization produced by a rapid retinal image
      displacement was examined in moving-background and saccadic eye movement
      experiments. In both experiments, the target for localization task and its
      background scene were dichoptically presented: they were presented separately to
      the different eyes. The error curves of mislocalization shown in the dichoptic
      viewing condition were the same as those in monocular viewing (in the moving
      background experiment) and binocular viewing conditions (in the saccadic eye
      movement experiment), indicating that in both experiments the neural interaction
      responsible for generating mislocalization took place at a site after the lateral
      geniculate nucleus in the visual system, not at the retinal level. Two possible
      explanations for mislocalization, one neurophysiological and the other cognitive,
      were proposed. Furthermore, it was established that the error curves of
      mislocalization are substantially different between the moving-background and the
      saccadic eye movement experiments: in the saccadic eye movement experiment, the
      error curves changed with the actual target position, but not in the moving
      background experiment. This was interpreted as showing that the basic mechanism
      for mislocalization is not the same between the two experimental situations.

PMID- 8533340
TI  - Tracking of illusory target motion: differences between gaze and head responses.
AB  - We compared ocular and eye-head tracking responses to an illusion of diagonal
      motion produced when vertical movement of a small visual target was synchronized
      to horizontal movement of a background display. In response to sinusoidal
      movement, smooth ocular pursuit followed vertical target motion, with only a
      small horizontal component. In response to regular stepping movement, all
      anticipatory saccades were in the direction of the illusion; these erroneous
      oblique movements were followed by corrective horizontal saccades. When the head
      was free to move, it usually showed a diagonal trajectory that, for both
      sinusoidal and stepping target motion, was always in the direction of the
      illusion; no corrective movements were present. Thus, for our illusory stimuli,
      eye and head tracking showed qualitative differences that imply that ocular
      tracking was ultimately controlled by actual target motion but head tracking was
      controlled by illusory target motion.

PMID- 8533341
TI  - Testing a computational model of light-adaptation dynamics.
AB  - Experiments from the periodic and aperiodic traditions were used to guide the
      development of a quantitatively valid model of light adaptation dynamics.
      Temporal contrast sensitivity data were collected over a range of 3 log units of
      mean luminance for sinusoids of 2 to 50 Hz. Probe thresholds on flashed
      backgrounds were collected over a range of stimulus-onset asynchronies and
      background intensities from 0.1 to 1000 td. All experiments were performed
      foveally in the photopic range and used a consistent stimulus paradigm and
      psychophysical method. The resulting model represents a merging of elements from
      both traditions, and consists of a frequency-dependent front-end followed by a
      subtractive process and static nonlinearity.

PMID- 8533342
TI  - Human efficiency for recognizing 3-D objects in luminance noise.
AB  - The purpose of this study was to establish how efficiently humans use visual
      information to recognize simple 3-D objects. The stimuli were computer-rendered
      images of four simple 3-D objects--wedge, cone, cylinder, and pyramid--each
      rendered from 8 randomly chosen viewing positions as shaded objects, line
      drawings, or silhouettes. The objects were presented in static, 2-D Gaussian
      luminance noise. The observer's task was to indicate which of the four objects
      had been presented. We obtained human contrast thresholds for recognition, and
      compared these to an ideal observer's thresholds to obtain efficiencies. In two
      auxiliary experiments, we measured efficiencies for object detection and letter
      recognition. Our results showed that human object-recognition efficiency is low
      (3-8%) when compared to efficiencies reported for some other visual-information
      processing tasks. The low efficiency means that human recognition performance is
      limited primarily by factors intrinsic to the observer rather than the
      information content of the stimuli. We found three factors that play a large role
      in accounting for low object-recognition efficiency: stimulus size, spatial
      uncertainty, and detection efficiency. Four other factors play a smaller role in
      limiting object-recognition efficiency: observers' internal noise, stimulus
      rendering condition, stimulus familiarity, and categorization across views.

PMID- 8533343
TI  - Effect of retinal image motion on visual acuity and contour interaction in
      congenital nystagmus.
AB  - This study determined how contour interaction (the degradation of visual acuity
      by the presence of nearby contours) is affected by the incessant retinal image
      motion that occurs in observers with congenital nystagmus (CN). Visual acuity was
      measured for single, high-contrast, black Landolt Cs, presented without and with
      flanking bars (contour-to-C separation = 1, 2, 5, or 10 multiples of the gap
      width of the C). Stimuli were presented against either a white or a black
      surround. For comparison, acuity was also determined in normal observers, with
      and without motion of the stimulus to simulate the retinal image motion in jerk
      CN. The results show that the peak magnitude of contour interaction (the maximal
      degradation in acuity attributable to contour interaction) is significantly
      larger in the observers with CN than in normals. When acuity targets are
      presented against a black surround, contour interaction also occurs over a wider
      spatial extent in the observers with CN. Imposed image motion increases the
      extent of contour interaction in normal observers, but not sufficiently to
      account fully for the results of the observers with CN. We suggest that the
      additional contour interaction found in observers with CN may be attributable to
      the presence of amblyopia. For a small contour-to-C separation, contour
      interaction is significantly greater when stimuli are presented against a black
      rather than a white surround. Consequently, single-letter acuity may be
      appreciably underestimated clinically when an adjustable window is used to
      isolate letters on a projected acuity chart.

PMID- 8533344
TI  - Photoreceptor spectral sensitivities: common shape in the long-wavelength region.
AB  - Previous measurements of mammalian photoreceptor spectral sensitivity have been
      analysed, with particular attention to the long-wavelength region. The
      measurements selected for study come from rod and cone systems, and from human,
      monkey, bovine and squirrel sources. For the spectra from photoreceptor
      electrophysiology and from psychophysical sensitivity, the frequency scaling
      applied by Mansfield (1985, The visual system, pp. 89-106. New York: Alan Liss)
      provides a common shape over a range of at least 7 log10 units of sensitivity,
      from low frequencies (long wavelengths) to frequencies beyond the peak. The same
      curve is applicable to the absorbance spectrum of bovine rhodopsin, although the
      absorbance can only be measured down to about 2 log10 units below the peak. At
      the longest wavelengths the results exhibit a common limiting slope of 70 loge
      units (or 30.4 log10 units) per unit of normalized frequency. A simple equation
      is presented as a generic description for the alpha-band of mammalian
      photoreceptor spectral sensitivity curves, and it seem likely that the equation
      may be equally applicable to retinal1-based pigments in other species. Despite
      the lack of a theoretical basis, the equation has the correct asymptotic
      behaviour at long wavelengths, and it provides an accurate description of the
      peak. It also accounts accurately for the experimentally observed "yellowing" of
      long-wavelength lights that occurs beyond 700 nm.

PMID- 8533345
TI  - An illusion of relative motion dependent upon spatial frequency and orientation.
AB  - Observers scanned a stationary pattern comprising a tilted sine-wave grating
      completely surrounding another grating of similar spatial frequency but tilted in
      the opposite direction (Fig. 2). They reported an illusory "sliding" motion of
      the inset grating with respect to the surround grating and the effect was clearly
      strongest for angles between the gratings of less than 60 degrees and for spatial
      frequencies between 6-11 cpd. In a second experiment, a similar pattern was moved
      (2.0 deg/sec) either up or down for a presentation time of 167 msec.
      Simultaneously, the inset grating was drifted at different speeds in each of its
      two directions. Using the method of constant stimuli, it was shown that the
      relative motion illusion could be cancelled by physically drifting the grating in
      the opposite direction to the illusory movement. The illusion arises because
      there is a failure to integrate two motion signals into the single motion vector
      which characterises rigid motion.

PMID- 8533346
TI  - Human cones appear to adapt at low light levels: measurements on the red-green
      detection mechanism.
AB  - Recent physiological evidence suggests that cones do not light adapt at low light
      levels. To assess whether adaptation is cone-selective at low light levels, the
      red-green detection mechanism was isolated. Thresholds were measured with a large
      test flash, which stimulated the L and M cones in different fixed amplitude
      ratios, on different colored adapting fields. Thresholds were plotted in L and M
      cone contrast coordinates. The red-green mechanism responded to an equally
      weighted difference of L and M cone contrast on each colored field, demonstrating
      equivalent, Weberian adaptation of the L and M cone signals. The L and M cone
      signals independently adapted for illuminance levels as low as 60 effective
      trolands (e.g. M-cone trolands). Since this adaptation is entirely selective to
      cone type, it suggests that the cones themselves light-adapt. The red-green
      detection contour on reddish fields was displaced further out from the origin of
      the cone contrast coordinates, revealing an additional sensitivity loss at a
      subsequent, spectrally-opponent site. This second-site effect may arise from a
      net "red" or "green" signal that represents the degree to which the L and M cones
      are differently hyperpolarized by the steady, colored adapting field. Such
      differential hyperpolarization is compatible with equivalent, Weberian adaptation
      of the L and M cones.

PMID- 8533347
TI  - The influence of two spatially distinct primers and attribute priming on motion
      induction.
AB  - In a series of experiments, we demonstrate the effects of two spatially distinct
      primers on motion induction (MI) and the influence of attribute characteristics
      on the resulting collision site. MI means that a primer such as a spot produces a
      motion sensation in a subsequently presented geometrical pattern such as a line
      or a rectangle. This pattern will appear to grow out of the spot. In the present
      paper we report that when two different locations of the visual field are
      activated simultaneously by presenting two spots prior to a bar between these
      spots, there is a motion sensation of two bars growing away from the spots and
      colliding in the centre (split priming effect). Attribute characteristics can
      have profound effects on this illusion. When two differently coloured isoluminant
      spots are presented and the subsequent bar is composed of either one of these
      colours, the induced motion is away from the spot of identical colour. We call
      this effect attribute priming. Manipulating the delay between the spot
      presentations (SOA) showed that timing had a strong effect on split priming, but
      very little on attribute priming. For split priming experiments with dichoptic
      presentations, we show that at shorter SOAs there is a dominant effect of the
      primer which is presented to the same eye as the bar, as opposed to the usual
      dominance of the later primer. For longer SOAs, however, the temporal sequence of
      the primers also plays a role in motion induction. Further, we report that
      geometrical arrangements can strongly influence the direction of perceived motion
      when more than a single primer is used. Generally, in motion induction with two
      primers, unlike what is found with a single primer, there appears to be a
      dominance of low-level effects such as geometry, attributes, and eye of
      presentation. For dichoptic presentations, however, this can be overcome for
      longer SOAs. The differences between the single and split priming paradigms are
      discussed in terms of the differential contribution of bottom-up and top-down
      processes.

PMID- 8533348
TI  - Discrimination of speed distributions: sensitivity to statistical properties.
AB  - Two experiments examining the ability of human observers to detect differences in
      the statistical properties underlying velocity distributions were conducted. A
      four-alternative forced-choice methodology, using four simultaneous velocity
      distributions, was used in both experiments. In the first experiment the value of
      one statistical moment (mean, variance, skewness, or kurtosis) was manipulated
      while the others were held constant. The subjects task was to determine which of
      four velocity distributions contained the dissimilar value. In the second
      experiment only the latter three moments were examined. A similar procedure was
      used, however feedback was given after each trial to maximize observer
      performance. The results from both experiments indicate that human observers can
      reliably detect differences in both mean and variance information underlying
      velocity distributions. The results of this research has important implications
      for image segmentation and the detection of heading from optic flow.

PMID- 8533349
TI  - Infant luminance and chromatic contrast sensitivity: optokinetic nystagmus data
      on 3-month-olds.
AB  - Infant color vision is poor, and most psychophysical experiments agree that
      infant color vision emerges between ages 3 weeks and 3 months. Presumably, the
      color vision of infants is poor during the months immediately after it has
      emerged. We have tested two alternative explanations for the poor color vision of
      infants: (1) there is a special critical immaturity within the color pathways of
      infants; (2) infants have poor infant color vision because they are insensitive
      to contrast. Luminance and chromatic contrast thresholds were measured on 3-month
      olds using optokinetic nystagmus (OKN), and adult luminance and chromatic
      contrast thresholds were measured using OKN and two forced-choice methods:
      direction-of-motion discrimination and grating detection. The infant chromatic-to
      luminance contrast threshold ratio shows that infants are as sensitive or even
      more sensitive than adults to color, depending on the testing method used on
      adults. This result suggests that the general contrast insensitivity hypothesis
      is correct. Conservative "worst-case" quantitative analysis strongly suggests
      that this result is not the consequence of a luminance artifact.

PMID- 8533350
TI  - Colour induced stereopsis in images with achromatic information and only one
      other colour.
AB  - Based on a model of transverse chromatic aberration (TCA) of the eye and
      perceptual effects previously discussed by the same author, it was predicted that
      colour induced binocular depth perception (chromostereopsis) is possible from
      images containing red or blue along with achromatic information (grey and black);
      that the direction of the perceived depth from certain colours should differ for
      the same TCA conditions; and that a greater depth perception should be possible
      in a blue/achromatic image than a red/achromatic image. Results of TCA
      manipulations support all three predictions and demonstrate that colour induced
      depth effects can be perceived in images having only achromatic information and a
      single non-achromatic colour. It is argued that optical factors, image
      characteristics and perceptual factors all play an important role in colour depth
      effects under natural viewing conditions. Further, the possibility is raised that
      colour and texture patterns which produce colour depth effects have evolved
      within certain species for camouflage or other behavioural purposes.

PMID- 8533351
TI  - Control of vertical eye alignment in three-dimensional space.
AB  - A target that is nearer to one eye than the other subtends a larger visual angle
      in the closer eye. Consequently, when making saccades between vertically
      separated targets that are closer to one eye, there is a vertical retinal
      disparity that must be overcome by a change in the relative alignment of the
      eyes. We recorded eye movements in three normal subjects and showed that in such
      viewing circumstances subjects made unequal vertical saccades that led to a rapid
      change (peak velocity up to 30 deg/sec) in vertical eye alignment. On average,
      81% of the required change in alignment occurred within the saccade for downward
      movements and 47% for upward movements. Such unequal vertical saccades occurred
      independently of immediate disparity cues; saccades remained unequal when
      refixing to the remembered locations of the vertically-oriented targets, or even
      when the natural vertical disparity was nullified by a prism. On the other hand,
      when subjects wore the nullifying prism in front of the inferior visual field of
      the left eye for 8-20 hr, they showed a decrease in saccade disconjugacy (to 12
      35% of the preadaptation value) to targets closer to the left eye in the inferior
      but not in the superior visual field. We suggest that the brain develops a three
      dimensional map (horizontal, vertical, depth) for vertical saccade yoking, which
      is under adaptive control, and which is used to preprogram automatically the
      relative excursions of the eyes during vertical saccades as a function of the
      current and the desired point of regard.

PMID- 8533352
TI  - Temporal coherence theory for the detection and measurement of visual motion.
AB  - A recent challenge to the completeness of some influential models of local-motion
      detection has come from experiments in which subjects had to detect a single dot
      moving along a trajectory amidst noise dots undergoing Brownian motion. We
      propose and test a new theory of the detection and measurement of visual motion,
      which can account for these signal-in-Brownian-noise experiments. The theory
      postulates that the signals from local-motion detectors are made coherent in
      space and time by a special purpose network, and that this coherence boosts
      signals of features moving along non-random trajectories over time. Two
      experiments were performed to estimate parameters and test the theory. These
      experiments showed that detection is impaired with increasing eccentricity, an
      effect that varies inversely with step size. They also showed that detection
      improves over durations extending to at least 600 msec. An implementation of the
      theory accounts for these psychophysical detection measurements.

PMID- 8533353
TI  - [The outlook for integrative work in the treatment and diagnosis departments of
      the A. A. Vishnevskii Central Military Clinical Hospital].

PMID- 8533354
TI  - [Improvement in integrative processes is the basis for raising the quality of
      radiodiagnosis in a general hospital].
AB  - The article is based on the retrospective analysis of a 5-year experience of work
      of the Vishnevskii Central Military Hospital roentgenological center which is
      composed of two roentgenological sections, as well as sections of angiography,
      ultrasonic, radiological diagnosis, etc. The trends for optimum functioning of
      this center were determined to enhance its capacities in the conditions of
      multipurpose hospital. It was marked that roentgenological center as a functional
      unit was an important part of medical diagnostical process. The main task of this
      center is to coordinate the work of sections of radiodiagnosis in order to make
      the more rational use of diagnostical methods.

PMID- 8533355
TI  - [The choice of the surgical assistance in perforated duodenal ulcers in
      servicemen on active duty].

PMID- 8533356
TI  - [The diagnosis and treatment of chronic critical ischemia of the extremities].
AB  - The article summarizes the experience of the vascular surgery unit of the
      Vishnevskii Central Military Hospital on treatment of 128 patients with chronic
      ischemia, namely atherosclerotic affection of aortofemorotibial segment. The
      authors show the important significance of the use of modern methods in studying
      the blood magistral and microcirculation. It is recommended to combine surgical
      and conservative treatment in order to preserve the affected limb. The article
      also contains determination and classification of chronic critical ischemia.

PMID- 8533358
TI  - [The current approach and basis for anesthesiological support in the surgical
      treatment of wounded patients at medical evacuation stages].

PMID- 8533357
TI  - [The detection and treatment of cancer of the large intestine].

PMID- 8533359
TI  - [The diagnosis, treatment and prevention of thromboembolism of the pulmonary
      artery in a general hospital].

PMID- 8533360
TI  - [The combined treatment of ischemic heart disease].

PMID- 8533361
TI  - [The medical service officers on the front lines in World War II].

PMID- 8533362
TI  - [The respiratory recovery therapy of respiratory failure in the sanatorium
      rehabilitation of pulmonary patients].

PMID- 8533363
TI  - [ECG changes during selective coronary angiography in patients with ischemic
      heart disease].

PMID- 8533364
TI  - [Experience in eliminating hospital salmonellosis in a large general treatment
      institution].
AB  - The author made a report on the results of epidemic examination of salmonellosis
      infection in a large medical institution. Peculiarities of the Salmonella
      typhimurium agent are described, as well as mechanism of transmission and most
      inflicted groups of patients. The factors which provided for proliferation of
      salmonellosis are depicted, taking into account the characteristic features of
      infectious process inside medical establishment.

PMID- 8533365
TI  - [The epidemiological significance of human lice in relation to the
      characteristics of their parasitism].
AB  - Epidemiological significance of clothes and head louse is determined first of all
      by the type of "parasite-host" connection. Clothes louse has an immediate contact
      with man only during bloodsucking, it dwells in clothes, consumes big portions of
      blood and has great productivity. Temperature factor is very important for
      Pediculus corporis. If the man's temperature is growing the louse will abandon
      him. The comparison of various literature data and proper author's information
      has shown that Pediculus capitis didn't play a significant role in epidemic
      typhoid malady taking into account the modern level of the affection of
      population with head lice. The author describes the peculiarities of morphology,
      biology, population dynamics, parasitology and epidemiology of P. capitis and P.
      corporis.

PMID- 8533366
TI  - [The epidemiological health surveillance of the working conditions for servicemen
      in weapons and military equipment parks].

PMID- 8533367
TI  - [The ecological hygienic assessment of radio engineering equipment as sources of
      electromagnetic radiations].

PMID- 8533368
TI  - [Medical support for the fleet forces of the Navy today].

PMID- 8533369
TI  - [The first dissertations by women physicians defended at the Military Medical
      Academy].

PMID- 8533370
TI  - [The status and developmental outlook of medical rehabilitation in pathology of
      the internal organs].

PMID- 8533371
TI  - [Wave processes in living tissues and their role in the damaging effect of modern
      small arms].

PMID- 8533372
TI  - [Angioneurosurgical care for patients with cerebrovascular pathology in a general
      hospital].

PMID- 8533373
TI  - [The successful treatment of a massive pulmonary artery embolism].

PMID- 8533374
TI  - [The treatment of inveterate combined injuries to the tendons of the deep flexors
      of the fingers and to the nerves of the hand].

PMID- 8533375
TI  - [An atypical course of chlamydial infection].
AB  - In Burdenko Main Military Clinical Hospital 113 patients with acute lung
      inflammations were examined. According to the data of serological tests with
      application of indirect immunofluorescent reaction an antibody titer (Chlamydia
      Pneumoniae) was disclosed in 9 patients (11% from the whole number of 82
      patients). By the authors' opinion bizarre and severe course of Chlamydia
      Pneumoniae could take place, thus, it is necessary to conduct serological
      examinations not only during epidemic outbreaks of acute respiratory diseases or
      pneumonias, but also during single cases of steady and long-term febrile diseases
      or protracted pulmonary inflammations.

PMID- 8533376
TI  - [Methods for DNA diagnosis in military medicine].
AB  - The article makes a review of achievements in the sphere of biotechnology and
      genetic engineering as far as military medicine is concerned. A special attention
      is drawn on diagnostic capacities of molecular genetic methods which analyse DNA
      and RNA objects. Principles of modern diagnostical methods are described which
      are based on molecular hybridization of nucleic acids with a use of specific DNA
      probes or polymerize chain reaction (PCR). The advantages of the latter are shown
      in the comparison with immunochemical methods. Peculiarities of new quantitative
      PCR modifications are studied. The article contains data concerning the use of
      DNA probes and PCR for estimation of radiation injuries and during formation of
      maximal tolerance level of physical and chemical influence.

PMID- 8533377
TI  - [Improvement in the system of checking and assessing the physical fitness of
      military physicians].
AB  - Problematic questions of physical training and physical fitness of military
      physicians are described in this article. The results of studies and estimation
      of the existing system of physical training of military physicians are depicted.
      Optimal fitness norms are recommended for MOS "Military physician".

PMID- 8533378
TI  - [The current status of the problem of parasitic diseases and their prevention].

PMID- 8533379
TI  - [The functional status of the body and work capacity of convalescent patients
      after typhoid fever].
AB  - Convalescents (168 patients) who went through typhoid and 48 sound men (control
      group) were examined in order to study their clinical and physiological indices,
      mental and performance capabilities. At the end of inpatient treatment the
      complete normalization of functional state was marked only in group 1
      (convalescents after abortive typhoid). In 96% of patients who went through
      slight form of disease (group 2) and middle-severe form (group 3) different
      disorders of functional state of organism were marked. One week after medical
      rehabilitation the number of convalescents who needed the continuation of
      rehabilitation treatment has decreased 50% in the 2nd group, after 2 weeks--up to
      35%, after 3 weeks there were no changes. In the 3rd group at the end of the 1st
      week functional disorders were marked in 85% of patients, after 2 weeks--in 35%,
      after 3 weeks--in 13.8%, after 4 weeks--in 2.5%.

PMID- 8533380
TI  - [A method for the dosage of drug ointments in tubes].

PMID- 8533381
TI  - [A field thermal air chamber for burn patients].

PMID- 8533382
TI  - [A device for managing attacks of bronchial asthma].

PMID- 8533383
TI  - [Generalizing from the experience of military epidemiologists during World War
      II].

PMID- 8533384
TI  - [The organization of medical care for women in the active army in 1941-1945].

PMID- 8533385
TI  - [The efficiency of using diagnostic methods in the polyclinic].
AB  - Due to the formation of consulting and diagnostic polyclinics (CDP) in the
      Russian Armed Forces the significance of multipurpose diagnostical process in
      military garrison has met a considerable upgrade. The authors take into account
      the experience of CDP work and recommend to make a rational centralization of
      diagnostical process and determine the outlook for the development of
      diagnostical technologies adapted for different polyclinics, making a rational
      use of modern diagnostical equipment and enhancing the qualification of personnel
      occupied with diagnostical work.

PMID- 8533386
TI  - [Selenium status of the inhabitants in the Kaluga region].
AB  - The human Se status of 8 areas of Kaluga region was studied. The mean serum Se
      levels 94 mg/l was significantly lower in the south compared to the northern area
      126 mg/l. Areas with radioactive pollution possessed higher percentage of persons
      with low serum Se concentration than in regions without the pollution. Negative
      influence of radiation on serum Se level was confirmed also by epidemiological
      data for workers of Chernobil NNP (65 mg/l-workers attending to the reactor and
      69 mg/l-for other employees). The same phenomenon was observed for males of Tula
      region who had taken part in the liquidation of an accident on the Chernobil NNP
      compared to other inhabitants of Tula region (78 mg/l and 89 mg/l
      correspondingly). The lowest antioxidant status (serum vitamin E, C and Se
      concentrations) in towns of Kaluga region with radioactive pollution possessed
      males of less than 60 years old.

PMID- 8533387
TI  - [Effects of multivitamin preparations enriched with Fe, Zn and Se on the selenium
      status of pregnant women].
AB  - Se status of Moscow pregnant women was studied. The 13% decrease of Se up to the
      30 week and the stability of GSHPx activity during all period of pregnancy were
      shown to be typical. No influence was found of the polyvitamine preparation
      action on Se status of women. The consumption of 30 mkg/day of Se during the
      pregnancy increased 2 times the GSPHx activity and conserved the serum selenium
      level.

PMID- 8533388
TI  - [Role of soybean proteins in human nutrition (review)].
AB  - Review. The analysis of a protein nutrition of Russia's population during last
      five years and ways of its rationalization are presented. The scientific
      background for prosperity of using of soy bean proteins, products of their
      processing and existing of products and half-finished products received from soy
      is given. Experimental data on biological value and bioavailability of soy bean
      proteins and results of clinical evaluation of curative and preventive effects of
      these various soy products are discussed.

PMID- 8533389
TI  - [Health survey of nitrate load in preschool institutions].
AB  - Consumption of nitrates with plant food, milk and water was studied in pre
      schoolchildren aged 4-6 years going to pre-school institutions. Contents of
      nitrates were higher than maximum permissible level in 25.3% of food samples. It
      was shown that most significant consumption of nitrates was at the expense of
      cabbage (1.9-2.4 mg/kg of body mass) and beetroot (1.5-2.0 mg/kg). Taking into
      account the nitrate levels in water and milk a daily consumption of nitrates in
      preschool children was higher than daily permissible level.

PMID- 8533390
TI  - [Providing adults and children with vitamin A and carotenoids in different
      regions of the CIS].
AB  - Population based studies of vitamin nutritional status in Russia, Ukranian,
      Belarus and Baltic States in 1983-1991 give evidence about satisfied vitamin A
      nutritional status and insufficient carotenoids nutrition of population. The
      retinol level below 30 MK2/dl (lower reference level) was revealed in 6% of the
      adults, 19% of the children and 6% of the pregnant women. The level of carotene
      below 80 MK2/dl took place in 39% of the adults, 28% of the children and 18% of
      the pregnant women. Worst vitamin A and carotene nutritional status was detected
      in adults and children living in Mogilevskaya and Gomelskaya regions suffering
      from accident on Chernobyl station as well as inhabitants of large industrial
      centres (Ekaterinburg, Orenburg, Kemerovo, Norilsk, Zaporoz'e) with bad
      ecological situation It was pointed on probable connection between insufficient
      consumption of carotene and increased risk of cancer and cardiovascular diseases.
      It is recommended the realization of large-scale actions upon cardinal
      improvement of vitamin A and carotene supplying of population.

PMID- 8533391
TI  - [New extrusion products in diet therapy of diseases of internal organs].
AB  - Therapeutic effectiveness of 3 new extrusion foods was studied in control
      conditions of clinic of Institute of nutrition RAMS. The foods were produced by
      Institute of meat industry RAS on basis of meat resources and wheat brans. The
      samples of extrusion foods were differed by contents of protein (17-23 g%) and
      dietary fibers (up to 10%) and used in therapeutic diet for patients with insulin
      dependent diabetes mellitus. It was shown that of all three extrusion foods
      caused decreasing of dyspeptic symptoms during first week of intake and
      normalisation of intestinal functions without using of laxatives unlike of
      control group of patients eating standard diabetic diet. It was shown also a
      decreasing of cholesterol in blood serum of patients received of extrusion foods
      No 1 and No 3. These samples are recommended for diet therapy and preventive
      nutrition of patients with metabolic disorders and hypomotoricity of intestinal
      tract as resources of dietary fibers and protein.

PMID- 8533392
TI  - [Bile-secreting function of the liver in patients with chronic alcoholism and
      ways of correcting it].
AB  - The examinations showed the differences in bile secretion and biochemical
      composition of bile in patients with chronic alcoholism II and III stages
      (respectively 1 and 2 groups of patients). The patients of group 1 have hypotonic
      gall-bladder with normal or in some cases increased speed of bile secretion with
      low contents of cholic acid, cholesterol and bilirubin. A type of bile secretion
      in patients group 2 is hypotonic-hypokinetic with patterns of bile stagnation.
      Treatment of patients of group 1 by cholenzyme and patients of group 2 by
      enterosorbent cholysorb promoted normalisation of intestinal circulation of bile
      components. Cholenzyme is remedy of compensation therapy and cholisorb allows to
      remove the bile stagnation.

PMID- 8533394
TI  - [Child nutrition in market economics].

PMID- 8533393
TI  - [New specialized milk product for nutrition of lactating women].

PMID- 8533395
TI  - [Problems in the development of infant foods technology].

PMID- 8533396
TI  - [Several problems of nutrition and health of children in the Russian North].
AB  - The article includes the developed analysis of the references and the results of
      private researches about the problems of nourishment and health of the boarding
      school's children from the Russian North. It is pointed out, that in the Northern
      district the children's nourishment must have a protein-lipid level. It is so
      that a ration carbo-hydrate level is not able for the child organism to adopt in
      the strong climatic conditions and has a negative effect for their physical state
      and health too. The retrospective analysis of nourishment is worked out according
      to boarding-school's children of Tajmir for the last 20 years.

PMID- 8533397
TI  - Two cases of malignant lymphoma complicating autoimmune (Hashimoto's)
      thyroiditis.
AB  - The occurrence of lymphoma of the thyroid in a setting of autoimmune thyroid
      disease is being recognized with increasing frequency. The usual presentation is
      a rapidly enlarging goiter. This article describes two cases of this condition
      and emphasizes how prompt diagnosis and treatment can yield satisfactory results.

PMID- 8533398
TI  - Radiofrequency catheter ablation in pediatric patients with supraventricular
      arrhythmias.
AB  - Radiofrequency (RF) ablation of foci leading to abnormal cardiac rhythms is
      rapidly becoming the procedure of choice in the management of arrhythmias in
      adults. This report reviews our initial experience with RF ablation in the
      pediatric population.

PMID- 8533399
TI  - At mother's mercy: the nightmare of Munchausen syndrome by proxy.
AB  - Munchausen syndrome by proxy is a form of child abuse in which a parent simulates
      or produces illness in a child for the purpose of engaging in a supportive
      relationship with a physician or other health care provider. The child suffers
      from the parent's actions and is subjected to significant morbidity due to
      extensive medical diagnostic procedures ordered by the unsuspecting physician.
      The purpose of this paper is to provide a better understanding of this disorder
      with respect to presentation, pathogenesis, and recognition.

PMID- 8533400
TI  - Three cases of hemorrhagic colitis in West Virginia due to Escherichia coli
      O157:H7.
AB  - Escherichia coli O157:H7 is an emerging cause of food-borne illness. This
      bacterial pathogen, most commonly transmitted by undercooked ground beef, causes
      hemorrhagic colitis. It has been associated with the hemolytic uremic syndrome
      and death, mostly in children and the elderly. This article describes three
      patients treated for sporadic cases of Escherichia coli O157:H7-associated
      hemorrhagic colitis at Charleston Area Medical Center over a three-week period.

PMID- 8533401
TI  - Response to treatment with progesterone in a patient with pulmonary
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is defined as an abnormal proliferation of smooth
      muscles around lymphatics, venules, and brochioles. This article describes our
      experiences treating a 21-year-old, white female who experienced recurrent
      shortness of breath during air travel last year. Her episode was severe and the
      patient was transported to the hospital as soon as the airplane landed. Physical
      exam in the emergency room was significant for absent breath sounds on the right
      side and the chest X-ray revealed a pneumothorax. She required two chest tubes
      for complete lung re-expansion. Further evaluation showed an obstructive pattern
      and air trapping on pulmonary function tests. This patient was treated with
      Medroxyprogesterone acetate (MPA) for six months and subsequent pulmonary
      function tests revealed improvement in her condition.

PMID- 8533402
TI  - Cortical blindness following cerebral angiography.
AB  - The use of radiological contrast agents is a common and necessary part of
      clinical medicine. Side effects of these agents are usually categorized as either
      allergic reaction including anaphylaxis, or specific organ system insult (i.e.
      renal impairment). A rare, but reported effect of vascular radiological contrast
      is transient cortical blindness.

PMID- 8533403
TI  - Time to stand up.

PMID- 8533404
TI  - Unintentional deaths from carbon monoxide poisoning in New Mexico, 1980 to 1988.
      A comparison of medical examiner and national mortality data.
AB  - Carbon monoxide was the number 1 cause of poisoning deaths in the United States
      from 1980 through 1988, with the highest rates reported in the western states. We
      studied unintentional deaths from carbon monoxide poisoning in New Mexico during
      this period using the multiple-cause mortality files from the National Center for
      Health Statistics (NCHS) and data from the New Mexico Office of the Medical
      Investigator (OMI). We compared the nationally available NCHS data with the more
      detailed OMI data to determine the sensitivity of NCHS data for the surveillance
      of this preventable cause of death. The NCHS data were 88% sensitive in
      identifying deaths from unintentional carbon monoxide poisoning and had a
      positive predictive value of 81% when compared with OMI data. Half of the
      unintentional carbon monoxide-related deaths were attributable to a home heating
      mechanism of some sort, 46% involved motor vehicle exhaust, and at least 42% were
      associated with alcohol use. We conclude that available NCHS data are a sensitive
      source of surveillance information about unintentional deaths from carbon
      monoxide poisoning. Additional details about specific deaths can be obtained from
      medical examiner files when needed.

PMID- 8533406
TI  - Drug-resistant Mycobacterium tuberculosis in California, 1991 to 1992.
AB  - To determine the proportion and distribution of drug-resistant Mycobacterium
      tuberculosis in California, we surveyed all California counties for drug
      susceptibility test results for initial isolates from tuberculosis cases counted
      during the first quarters of 1991 and 1992. Overall, drug-susceptibility test
      results were not available for 17% of isolates. Among isolates with available
      test results, the proportion with resistance to isoniazid averaged 8.7%, and the
      proportion with resistance to at least 2 drugs, multidrug resistance, averaged
      5.9% during these two quarters. The proportion of isolates with drug resistance
      did not change substantially during these time periods. The proportion with
      combined isoniazid and rifampin resistance remained stable at about 1.1%. Among
      persons whose isolates were tested for drug resistance, those with a known
      previous diagnosis of tuberculosis (relative risk [RR] = 2.6; 95% confidence
      interval [CI], 1.6 to 4.3; P < .01) and persons who were foreign born (RR = 1.7;
      95% CI, 1.1 to 2.7; P = .014) were more likely to have isoniazid-resistant
      organisms. These statewide data suggest that the initial tuberculosis treatment
      regimen in California should include 4 antituberculosis drugs, as recommended by
      the American Thoracic Society and the Centers for Disease Control and Prevention
      for areas with a prevalence of isoniazid resistance of 4% or greater. The lack of
      test results for 1 in 6 patients with tuberculosis suggests the need for improved
      physician and laboratorian education to implement the recommendations that drug
      susceptibility be tested on all initial isolates.

PMID- 8533405
TI  - Drugs, poverty, pregnancy, and foster care in Los Angeles, California, 1989 to
      1991.
AB  - To determine the characteristics and childbearing histories of women whose
      infants entered foster care in Los Angeles County, we examined the cases of 1,155
      drug-using women whose infants were removed from them at birth and 236 non-drug
      using women whose infants were also removed at birth by court order (July 1989
      through March 1991). All of the women were indigent, and less than half had
      graduated from high school. The drug-using women frequently had criminal records,
      and more than a quarter were homeless. Many comparison women had mental health
      problems, and some (16.7%) were teenagers under court custody. Overall, 80% of
      all the children born to both groups of women were under court jurisdiction. Data
      obtained after study infants' births on 926 drug-using women observed for 18
      months revealed that 22% had borne another infant who was placed in foster care;
      half of these infants had a positive drug immunoassay. Of the 185 non-drug-using
      women with 18-month follow-ups, 7.6% had borne another child who was in foster
      care. The magnitude of the repeated childbearing recorded among both groups of
      women in this study shows that preventive programs including family planning,
      mental health services, and drug prevention or rehabilitation programs have not
      reached this population.

PMID- 8533407
TI  - Varicella during pregnancy. Maternal and fetal effects.
AB  - To determine the characteristics of maternal varicella at our institution, we
      reviewed all cases of primary varicella in pregnancy. Using a perinatal database
      that summarizes all obstetric admissions, we reviewed the medical records of
      women with varicella infections during pregnancy. Over a 5 1/2-year period, 31
      pregnancies were affected by varicella infection among 11,753 deliveries. The
      mean age of those patients was 19.6 years, significantly different from our
      overall population of 25.3 years (P < .05). The racial composition of 35%
      Hispanic, 35% white, and 29% African American was different from that of our
      general population of 55% white, 38% African American, and 6% Hispanic (P =
      .023). The mean gestational age of the eruption of vesicles was 25 weeks. Of the
      31 women, 7 had preterm labor within a week of their varicella, 3 delivered
      prematurely, and 3 infants had a birth weight of less than 2,700 grams.
      Respiratory symptoms developed in 6 women, and pneumonia developed in 4, 2 of
      whom required ventilatory support, 1 for 5 days, the other for 49 days. Eight
      women received acyclovir during gestation, and none suffered sequelae. In all, 6
      infants had lesions and anomalies noted at birth, 5 possibly associated with
      varicella. Varicella infection is associated with a greater-than-expected level
      of both maternal and fetal morbidity. The fetal disease may occur due to maternal
      infection at any gestation and is most likely a spectrum of complications. The
      maternal disease appears to be worse in the latter half of pregnancy. Programs of
      prevention through vaccination must account for a possibly decreased level of
      immunity in different populations.

PMID- 8533408
TI  - Colorado pediatricians' involvement in community activities.
AB  - To determine Colorado American Academy of Pediatrics (AAP) pediatricians'
      involvement in community-based activities and awareness of and interest in the
      AAP Community Access to Child Health (CATCH) program, a 22-item survey was mailed
      to all general pediatrician AAP fellows and candidate fellows practicing in
      Colorado (n = 434). The return rate was 65%. Of the respondents, 73% provide
      direct patient care as their primary professional activity, 58% reported either
      current or past involvement in community-based programs outside of their
      practices, 91% of this community-based work was voluntary, and 80% of the
      respondents described this work as moderate to very rewarding. Half of the
      respondents (51%) were aware of the AAP CATCH program, and 68% were interested in
      attending a statewide CATCH meeting. We conclude that Colorado AAP pediatrician
      survey respondents participate heavily in community programs outside of their
      clinical practices and that among this group there is substantial interest in the
      AAP CATCH program.

PMID- 8533410
TI  - Unproven (questionable) cancer therapies.
AB  - More than half of all cancer patients use some form of alternative treatment
      during the course of their illness. Alternative therapies are often started early
      in patients' illness, and their use is frequently not acknowledged to health care
      professionals. Some alternative therapies are harmful, and their promoters may be
      fraudulent. Persons who try alternative cancer therapies may not be poorly
      educated but may ultimately abandon conventional treatment. Recent attention has
      focused on aspects of questionable therapies that make these treatments
      attractive to patients and that may be perceived as being deficient in the
      practice of conventional health care professionals. Physicians with patients with
      cancer should always make sure that unproven therapies are discussed early in the
      therapeutic relationship. They should also attempt to be aware of alternative
      therapies that are in vogue in their particular geographic area.

PMID- 8533409
TI  - Neuroendocrine disorders of the gut.
AB  - The regulation of gastrointestinal function is known to involve elements of the
      enteric nervous system. Processes such as secretion, motility, blood flow, and
      immune function are all influenced by a complex network of neurons whose cell
      bodies lie in the gut. These neurons use a wide spectrum of substances as
      neurotransmitters, although the majority use peptides once thought to function
      only as gut hormones. It has been increasingly recognized that abnormalities of
      this neuroendocrine regulatory system underlie many gastrointestinal disorders.
      The most obvious are states of peptide excess found in patients with gut
      endocrine tumors such as carcinoid, gastrinoma, and somatostatinoma. Conversely,
      other disorders appear to be related to deficiency states. Examples include both
      achalasia and Hirschsprung's disease (congenital megacolon), where the loss of
      inhibitory neural action leads to abnormalities of peristalsis and sphincter
      function. Evidence for abnormal neuroendocrine regulation leading to disease
      states is increasing for many other gastrointestinal disorders.

PMID- 8533411
TI  - Neurology of human immunodeficiency virus infection--past, present, and future.

PMID- 8533412
TI  - Emerging therapies for acute stroke.

PMID- 8533413
TI  - Development of botulinum toxin therapy.

PMID- 8533414
TI  - Multiple sclerosis.

PMID- 8533415
TI  - Dementia--an update.

PMID- 8533416
TI  - Headache.

PMID- 8533417
TI  - New antiepileptic medications.

PMID- 8533418
TI  - Glutaraldehyde proctitis.

PMID- 8533419
TI  - Adult obstructive sleep apnea with secondary enuresis.

PMID- 8533420
TI  - Toxic 'sock' syndrome bezoar formation and pancreatitis associated with iron
      deficiency and pica.

PMID- 8533421
TI  - A picture is worth a thousand words.

PMID- 8533422
TI  - Chemical messengers of the gut.

PMID- 8533423
TI  - Patients from Japan and physician-patient communication.

PMID- 8533424
TI  - Salty milk--when to worry.

PMID- 8533425
TI  - Congenital heart disease in adults.
AB  - Patients reaching adulthood with unoperated and operated congenital heart disease
      require attention to issues of exercise, antibiotic prophylaxis, contraception,
      and pregnancy. A careful clinical history is important to establish the degree of
      a person's disability, if any, and the symptoms responsible for the disability,
      whether due to heart failure, cyanosis, or both. The findings of a physical
      examination and a noninvasive evaluation, including electrocardiogram, chest x
      ray film, and echocardiography, are often sufficient to establish a diagnosis and
      to assess the adequacy of a previous operation. Transesophageal echocardiography
      and magnetic resonance imaging are adjunctive procedures that are indicated when
      routine transthoracic echocardiography is limited. Cardiac catheterization may be
      necessary when the noninvasive data are ambiguous and to assess coronary artery
      disease (congenital and acquired) in patients considered for surgical therapy.
      Cardiac catheterization is increasingly therapeutic (such as percutaneous
      pulmonary balloon valvuloplasty) as well as diagnostic. Primary surgical repair
      or additional surgical palliative procedures should be considered in symptomatic
      adults. A patient with Eisenmenger's syndrome--severe pulmonary hypertension--is
      a special case that may be amenable only to transplantation.

PMID- 8533426
TI  - Biochemical aspects of iron metabolism, transport and regulation.
AB  - Iron metabolism in man is controlled by homeostatic mechanisms mainly based on
      intracellular regulation of iron uptake, utilisation and storage. Despite
      impressive accumulation of knowledge in recent years, the question how iron
      actually passes cellular membranes and how this transport process is regulated
      remains largely unanswered. Various models and hypotheses are discussed in
      context with other well established features of iron homeostasis.

PMID- 8533427
TI  - Nucleobase and nucleoside transport in mammalian cells.
AB  - Membrane transport of nucleobases and nucleosides has been an actively pursued
      research field for the past 25 years. Not only are these substances of
      physiological interest; derivatives are in clinical use or under investigation
      for their pharmacological activity against viral and neoplastic disease. An
      understanding of the molecular pharmacology of these substances includes a
      detailed knowledge of how they reach their intracellular targets. Membrane
      transport systems which have so far been found in all cells examined play an
      important role in this process. Since the transporters are minor membrane
      components, little is known about them on a molecular basis. This review
      discusses methodological approaches used to measure initial rates of membrane
      transport and summarizes current knowledge of the various transport systems which
      have been characterized with these kinetic methods.

PMID- 8533428
TI  - Structure-activity-relationship studies on modulators of the multidrug
      transporter P-glycoprotein--an overview.
AB  - Resistance of tumor cells to a wide variety of cytotoxic agents represents a
      major problem in cancer therapy. In most cases, the cross resistance profile has
      been shown to be accompanied by a decrease in drug accumulation in the resistant
      cells. At present it seems to be widely accepted that this decrease in
      intracellular drug levels is due to active efflux of these drugs caused by P
      glycoprotein (PGP). Within the past decade, several substances have been
      identified as being capable of inhibiting the active drug efflux caused by P
      glycoprotein. Although many excellent reviews on the phenomenon of multidrug
      resistance (MDR) have been published, little is known about SAR (Structure
      Activity-Relationship)- or QSAR (Quantitative-Structure-Activity-Relationship)
      studies of modulators of MDR. The aim of this article is to review first results
      in this field.

PMID- 8533429
TI  - Modulation of biological tyrosine reactions by tyrosine phosphorylation.
AB  - This review focuses on the influence of tyrosine phosphorylation on the
      biological reactions of tyrosine. Reactions that are modulated by this amino acid
      modification include dityrosine formation, thyroid hormone synthesis, and DOPA
      formation. In addition, we show that the reactivity of tyrosine in the common
      Lowry method of determination of protein concentrations is lost upon
      phosphorylation of the amino acid.

PMID- 8533430
TI  - [Peroxisomal diseases--oxygen and free radicals].
AB  - Peroxisomes were the latest subcellular organelles to be discovered. For a long
      time, due to limited knowledge of their function, peroxisomes were considered to
      play only a supporting role for other organelles in cellular metabolism. The
      discovery of specific metabolic pathways carried out exclusively in peroxisomes
      and, in particular, the description of genetically determined peroxisomal
      disorders such as the Zellweger syndrome and X-linked adrenoleukodystrophy,
      established the importance of these organelles in playing an essential role in
      cellular metabolism. Recently, their participation in the metabolism of reactive
      oxygen species and free radicals was found to be one of the important functions
      of peroxisomes. The fact that peroxisomal disorders are well defined
      biochemically and that peroxisomes consume a significant amount of the total
      cellular oxygen uptake, make cells from patients suffering from these disorders a
      suitable cell model for studying peroxisomal participation in the detoxification
      of reactive oxygen species.

PMID- 8533431
TI  - [The ribonucleotide reductase enzyme as a target for enzyme-directed chemotherapy
      effects of trimidox (3,4,5-trihydroxybenzohydroxamidoxim), a new inhibitor of
      ribonucleotide reductases].
AB  - Inhibition of the enzyme ribonucleotide reductase by polyhydroxy-substituted
      benzohydroxamide derivates is an example for the effects of antimetabolites. We
      present an overview of the effects of antimetabolites, in particular regarding
      their action on leukemia cells. Trimidox is one of the most effective inhibitors
      of ribonucleotide reductase. It inhibits the enzyme in cell extracts as well as
      in the in situ assay and causes decreased dGTP and dCTP pools in HL-60 cells. We
      describe combinations with other antimetabolites, as well as biochemical,
      morphological and cytotoxic effects of trimidox. This manuscript gives an
      overview of our results with trimidox and describes selection criteria, effects
      and combinations used in enzyme-targeted chemotherapy.

PMID- 8533432
TI  - [Mucopolysaccharidoses--current aspects of diagnosis and therapy].
AB  - The mucopolysaccharidoses, first described at the beginning of this century, are
      still subject of research. The accumulation of pathological metabolites and the
      underlying enzyme defects are now correlated to specific gene mutations. A
      comparison of genotype and phenotype of the individual forms of the
      mucopolysaccharidoses is the subject of ongoing studies. In many cases,
      symptomatic treatment was not able to increase the quality of life of patients
      suffering from mucopolysaccharidosis to a satisfactory degree. International
      working groups are, thus, currently trying to improve and standardize symptomatic
      therapies. A causal therapeutic approach was attempted by implanting different
      cells and tissues that are able to produce the missing enzymes. Bone-marrow
      transplantations were also performed, but both treatment approaches were not very
      effective and in some cases even proved fatal for the patients. An intensive
      international research effort focuses on enzyme-replacement therapy and gene
      therapy. Mucopolysaccharidoses are rare diseases, affecting only about one
      hundred patients in Austria. Nevertheless, Austria plays an active role in
      researching these metabolic disorders.

PMID- 8533433
TI  - [Methodologic decisions in evaluation of psychotherapy].
AB  - Psychotherapy research makes demands on evaluation studies in regard to content
      and methodology. These demands, however, are difficult to realize. The expense of
      a study results in a multidimensional matrix consisting of: the different sources
      of data, number and extent of the measures on theoretically derived assessment
      levels, the number of times measures are repeated, and the sample size. Decisions
      for research methods should be deduced explicitly from the goal of the evaluation
      study as well as from the goals of the evaluated therapy. Alternatives for the
      choice of operationalization, test designs, data evaluation and presentation will
      be reviewed and discussed.

PMID- 8533434
TI  - [The Parent Questionnaire in Family-Oriented Rehabilitation/Oncology--an
      instrument for inpatient quality assurance].
AB  - Improved long-term survival rates in childhood cancer have resulted in an
      increased demand for family-centered care programs. The EFR-O was developed as a
      screening-instrument tapping parental stressors and resources. The instrument was
      designed in order to assist family health care providers in allocating parents to
      need-centered rehabilitation services.

PMID- 8533435
TI  - [Emotion-focused couples therapy--treatment approach--evaluating effectiveness
      and process research].
AB  - Emotionally-Focused Couple/Marital Therapy will be examined and discussed in
      terms of methods of treatment, its effectiveness and underlying therapy
      processes. Four different evaluation studies have demonstrated the effectiveness
      of Emotionally-Focused Couple/Marital Therapy when used to resolve difficulties
      between couples with slight to moderately severe problems relatively in regard to
      pertinent treatment alternatives and absolutely in comparision to nontreatment.
      In addition, its clinical relevance has been demonstrated. Moreover, five studies
      on the investigation of procedures have reached conclusions which concur with the
      theory of treatment postulated.

PMID- 8533436
TI  - [With problem of applying modern systems theories in clinical practice].
AB  - In this paper the tension between "practice" and "theory" is reflected concerning
      modern system theories and psychosocial practice. Focusing the limits of
      predictability and manageability these theories contrast with practitioners need
      for easy-to-use advices for acting. Reframing the well-known dilemma of the
      discrepancy between theory and practice the usefulness of the difference between
      theory and practice is accentuated. Others reflected these topic in more
      fundamental or philosophical way (cf. Krohn & Kuppers 1990; Schiepek 1991;
      Schiepek, Fricke & Kaimer 1992; Willke 1989). In a more "pragmatic turn"
      attention is drawn to some methods of orientation and intervention in complex
      systems. System game and system competence are new ways in training and
      evaluating the management of complex systems.

PMID- 8533437
TI  - [Perspectives and time as relevant phenomena in the psychopathology of obsessive
      compulsive neuroses].
AB  - Perspectivity and time are central terms of the process of cognition in the
      phanomenological philosophy and anthropology. In this context, "perspective"'
      means the terms of freedom, act, orientation and sense. The "world of obessional
      neurotic" however is characterized by the lack of intersubjective relations, by
      loss of orientation and senselessness. The time, which the obessional neurotic
      experienced not as continual protention, but by compulsive rituals and
      compulsions of control, did deprive him of each liberal relation to future. From
      this context implications for a psychotherapeutic relation can be derived.

PMID- 8533438
TI  - [How can acceptance by psychiatric patients of group psychotherapy be improved?
      An empirical study of the effect of combined individual and group psychotherapy
      on attitude to group psychotherapy].
AB  - This study investigates whether the sceptic attitude of many psychiatric patients
      to group therapy can be improved by a combined individual and group therapy
      program. The investigation was made on 50 patients, most of them with neurotic
      disorders, partly with secondary alcohol or substance abuse as well as some
      schizophrenic patients. Before admittance to the psychotherapy program enquiries
      were made by means of a questionnaire, about what subject they would like to
      speak in the individual or group therapy sessions. The results differ
      significantly dependent on sociodemographic and illness related factors. A second
      examination after discharge reveals an ameliorated attitude concerning group
      therapy in nearly all central themes. Thus, one of the important goals of in
      patient psychotherapy has been achieved to improve patients ability to receive
      out-patient group therapy.

PMID- 8533440
TI  - Classification of vasculitides. A survey.
AB  - Many proposals for the classification of vasculitides have been presented but
      none have been universally recognized. This survey deals critically with the
      recently proposed nomenclatures and shows up their advantages and disadvantages.
      Finally a new trial is presented which includes also phlebitic and lymphangitic
      disease entities and tries to consider all known vasculitic disease entities.

PMID- 8533439
TI  - Classification and grading of chronic venous disease in the lower limbs--a
      consensus statement. Organized by Straub Foundation with the cooperation of the
      American Venous Forum at the 6th annual meeting, February 22-25, 1994, Maui,
      Hawaii.

PMID- 8533441
TI  - [Ultrastructural characteristics of cellular reaction to experimental catheter
      induced lesions of arterial blood vessels].
AB  - After angioplasty, restenosis remains the major drawback of the procedure with an
      incidence of between 20-40%. It is a matter of concern whether the cellular
      alterations start immediately after directional atherectomy (DA) and if they are
      dependent on the depth of the lesion. METHOD: Cellular alterations immediately
      after DA were investigated using peripheral atherectomy in normal vessels of 30
      pigs (A. femoralis, A. carotis communis). DA was used to remove material. The
      arteries were assigned to two groups according to the depth of vessel injury.
      (Group 1: lesions to the intima; Group 2: lesions to the media.) 68 arteries with
      41 intimal and 27 media lacerations were excised 4 to 24 hours later and
      processed for transmission electron microscopy, histology and
      immunohistochemistry. RESULTS: Immediately after DA, thrombus formation at the
      site of the altered segment was found. A transient infiltration of
      polymorphonuclear leukocytes (PMN) occurred, especially if the media was
      lacerated, followed by the transformation of contractile smooth muscle cells
      (SMC) into the synthetic subtype. A marked myoproliferative response was found in
      Group 2 whereas only moderate tissue hyperplasia was seen in Group 1. CONCLUSION:
      The present data provides evidence that cellular alteration of the atherectomized
      vessel begins immediately after atherectomy. Subsequent to the initial temporary
      PMN infiltration, an activation of local SMC occurs at a very early stage. These
      effects and, in particular, a myoproliferative response were found lesions
      injured the internal elastic membrane, while only minor effects were seen when
      the lesion affected the intimal layer.

PMID- 8533442
TI  - PGE0 inhibits collagen and glycosaminoglycan-synthesis in the rabbit arterial
      wall.
AB  - The influence of 13,14-dihydro-PGE1 (PGE0), a biologically active metabolite of
      PGE1, on collagen and glycosaminoglycan synthesis by the rabbit arterial wall was
      assessed and compared with the effect of PGE1. Collagen (COL) and
      glycosaminoglycan (GAG) synthesis was measured using 14C proline- and 35S
      incorporation respectively and both were subsequently quantified by
      autoradiography. PGE1 decreased GAG-synthesis by 40%, while PGE0 caused a 25%
      decrease. COL-synthesis after PGE1 treatment was diminished by 35%, while the
      biologically active metabolite caused a drop of 30%. Five and 15 micrograms/kg
      doses of both compounds were almost equally effective, 1 microgram was without
      effect. These findings indicate that PGE0 shares the inhibitory effect of PGE1 on
      COL and GAG biosynthesis. This metabolite has about 60 to 70% of the biological
      activity of its parent compound PGE1. These results suggest that part of the
      effects of PGE1 in inhibiting extracellular matrix production could be due to its
      metabolite PGE0.

PMID- 8533443
TI  - [Noise-induced changed in basilar circulation].
AB  - In 55 volunteers with good hearing, sound-evoked changes in the blood flow of the
      basilar artery were studied using colour coded Doppler sonography. After a rest
      of twenty minutes 2 groups of subjects listened to sound of varying volume using
      a head phone. In one group (n = 25) the sound volume was 25 dB and in the second
      group (n = 30) the volume was 65 dB. In both groups significant sound evoked
      changes of vascular resistance were found, quantified by the RI. In the case of
      applying soft sound (25 dB) the RI decreased, indicating an increase of volume
      flow while with louder sound (65 dB) the RI increased, indicating a reduction of
      flow.

PMID- 8533444
TI  - Influence of diabetic neuropathy on skin microcirculation assessed by
      transcutaneous oxymetry.
AB  - Skin microcirculation was investigated in 45 patients with long term diabetes and
      with severe, moderate or no neuropathy, and in 15 controls. Transcutaneous oxygen
      pressure (tcPO2) measurements on the forefoot were performed at 37 degrees C to
      assess local capillary flow at rest, during leg dependency and reactive
      hyperaemia, and also at 44 degrees C, including the response to oxygen
      inhalation. TcPO2 (37 degrees C) at rest was significantly elevated with an
      increasing degree of neuropathy (Controls: 4.8 +/- 3.7; patients without
      neuropathy: 4.2 +/- 2.9; with moderate neuropathy: 6.0 +/- 2.9 (p < 0.01); with
      severe neuropathy: 7.2 +/- 4.2 mmHg (p < 0.001)). Leg dependency resulted in a
      decrease of tcPO2 in the controls, while an increase was observed in 18.6% of the
      measurements in patients, reflecting a disturbed vasoconstrictor response.
      Regardless of neuropathy, absolute tcPO2 values during reactive hyperaemia were
      reduced in all patient groups as well as tcPO2 (44 degrees C) and its increase
      during oxygen breathing. Diabetic neuropathy is likely to increase local
      capillary flow, while the other differences to healthy controls may be
      contributed to a microcirculation disorder independent of neuropathy.

PMID- 8533445
TI  - [Thrombomodulin is a marker of microvascular, but not for macrovascular
      endothelial cell damage].
AB  - Plasma levels of thrombomodulin are increased in diseases associated with
      microangiopathia. The target of this study was to examine whether plasma
      thrombomodulin is also influenced by macroangiopathia. There was no variation of
      plasma thrombomodulin in a sample of 183 diabetic patients with or without
      peripheral arterio-occlusive disease of the lower limbs. In a second sample of 33
      patients with peripheral arteriosclerosis of the lower limbs, without any
      indication of diabetes, plasma levels of thrombomodulin were not significantly
      increased compared to a control group. Since thrombomodulin is also found in
      thrombocytes, we analysed whether plasma thrombomodulin levels were influenced by
      platelet activation. Neither platelet activation after hyperthermal limb
      perfusion not the PGE1-treatment showed any effect on plasma thrombomodulin
      level. CONCLUSION: Thrombomodulin is a marker for microvascular but not for
      macrovascular endothelial cell damage.

PMID- 8533446
TI  - [Aortocolic fistula as a rare complication of aorto-iliac aneurysms].
AB  - Primary aortocolic fistula is a rare complication of infrarenal abdominal aortic
      aneurysm. Many case reports have been published along with small series but the
      incidence of primary aortocolic fistulae remains unknown. In contrast, the
      incidence of secondary aortocolic fistulae increases approximately up to 1.5-4.0%
      as a result of rapid evolution of aorto-iliac vascular reconstruction with
      prosthetic grafts. The prognosis of aortocolic fistulae mainly depends on the
      time interval between first clinical manifestations and operative treatment. Loss
      of time by detailed preoperative investigations worsens the critical situation of
      the patient. The high mortality is mainly due to the sequelae of hemorrhagic
      shock, and in a lesser degree to graft infection. Therefore the principal
      operative treatment is to stop bleeding in order to reduce the sequelae of
      hemorrhagic shock. The method of choice for vascular reconstruction is the extra
      anatomic axillobifemoral bypass as a time-saving and uncomplicated operation to
      avoid fatal graft infection and to ensure sufficient arterial blood supply to the
      lower limbs. Any enteral bleeding of patients with aorto-iliac aneurysm or with a
      history of aorto-iliac prosthetic substitution has to be considered as an
      aortointestinal or an aortocolic fistula until the opposite is proven. This
      consideration is decisive for the prognosis of aortocolic fistulae. The operation
      treatment of all diagnosed aorto-iliac aneurysms, as well as the ultrasound
      control of all aorto-iliac prosthetic reconstructions, are possible preventive
      measures.

PMID- 8533447
TI  - Prediction of early cardiac morbidity and mortality following aorto-iliac
      reconstruction: comparison between clinical scoring systems, echocardiography and
      dipyridamole-thallium scanning.
AB  - Preoperative cardiac assessment may be difficult in patients with aorto-iliac
      and/or peripheral vascular disease because of severe physical limitation due to
      the disease itself, advanced age, locomotor problems or because of beta-blocker
      usage. 216 patients with aorto-iliac occlusive disease were studied; several
      cardiac risk scoring systems were determined for each patient. Preoperative
      echocardiography was performed in 182 patients and thallium-scanning in 63
      patients. The results from the preoperative risk factor evaluations,
      echocardiographies and thallium examinations were correlated individually with
      the postoperative observed cardiac complications. Overall mortality was 2.8% (4
      patients died from myocardial infarction). A total of 13 major postoperative
      cardiac events (10 myocardial infarctions and 3 life-threatening arrhythmias)
      were registered. No statistical correlation could be identified between the
      patient's clinical examination nor the scoring system and the occurrence of
      postoperative cardiac complications. 12 events occurred out of 13 patients who
      were shown to have a reversible defect on the preoperative thallium scan. These
      patients also presented hypokinesia or akinesia on the preoperative
      echocardiography. Thallium imaging and echocardiography represent a valid
      preoperative test to evaluate the risk of cardiac morbidity and mortality in
      vascular patients. Coronary angiography is recommended in patients suffering from
      progressive and/or unstable angina.

PMID- 8533448
TI  - [Transgenicular amputation with special reference to partial secondary femoral
      condyle resection].
AB  - During the last five years 54 patients (mean age 69 years) have undergone a
      unilateral, transgenicular (through-knee) amputation, instead of an impending
      amputation through the thigh. The indication for surgery was a chronic, or an
      acute critical ischemia of the leg. In 32 and 22 cases respectively, amputations
      have been preceded by a multitude of reconstructive measures. Uncomplicated stump
      healing was observed in 25 of 51 survivors (49%). Disturbances in the wound
      healing process necessitated further amputation in 26 cases (51%). In 13 of these
      cases the advantage of the transgenicular amputation could be retained by a
      partial femoral condylectomy, whereas in the other 13 cases a thigh amputation
      was inavoidable. Thus, in three out of four of the survivors, a long, strong
      stump with a good terminal load-carrying capacity could be retained which, when
      supplied by a prosthesis, led to the recovery of the original walking ability in
      90% of these cases.

PMID- 8533449
TI  - [Isolated, true aneurysm of the tibiofibular trunk--a rarity among peripheral
      aneurysms].
AB  - A 63-year-old patient presented with an arteriosclerotic aneurysm of the
      tibiofibular trunk. The clinical symptoms included microembolism into the distal
      lower leg (pedal arteries). The surgical treatment consisted of a venous
      interponate between the tibiofibular trunk and the posterior tibial artery. Due
      to the high complication rate by microemboli, surgical treatment of peripheral
      aneurysms by a venous bypass is indicated.

PMID- 8533450
TI  - [Chylous ascites, a rare complication of aortic surgery].
AB  - Less than 1% of all complications following vascular surgery of the abdominal
      aorta involve the lymphatic system. We report on a case of Chylous ascites
      following the operation of a ruptured infrarenal aortic aneurysm. The primary
      therapy, administered over a period of five weeks, consistent of diuretics and
      substitution by human albumin. However, the chylous flow did not decrease. A
      surgical intervention by a retroperitoneal ligation to try to stop the lymph flow
      also failed. Finally a total parental nutrition was followed by decrease and
      arrest of the lymph flow. Conservative treatment of this complication is
      considered as therapy of choice.

PMID- 8533451
TI  - Haemorrhage due to laceration of an aberrant inferior epigastric artery during
      femoropopliteal PTA in an obese patient; a rare complication of a high antegrade
      femoral puncture.
AB  - Haemorrhage due to laceration of the proximal inferior epigastric artery during
      femoro-popliteal PTA in an obese 79-year-old woman is reported as a rare
      complication of a high antegrade femoral puncture. The post procedural
      haemorrhage was caused by a high antegrade puncture lacerating a low overriding
      inferior epigastric artery.

PMID- 8533452
TI  - [Recurrent thromboses in a 32-year-old pregnant patient with permanent vena cava
      filter].
AB  - Vena cava-filters are implanted where there is a risk of pulmonary embolisation
      as cases of thrombosis. Permanent vena cava-filters can induce various
      complications during the remainder of the patient's life. A case of a 32-year-old
      woman who became pregnant seven years after the implantation of a Kimray
      Greenfield-Filter and gave birth to a healthy child is presented. During
      pregnancy and after the birth of a healthy child she suffered from two new
      thrombotic events. After the delivery, a complete thrombosis of the vena cava
      inferior, both venae iliacae communes and the right vena renalis were shown by
      computer-tomography and phlebography. Inspite of these longterm complications,
      pregnancy is not contraindicated after implantation of a permanent vena cava
      filter.

PMID- 8533453
TI  - [Transfemoral fenestration and stent implantation in aorto-iliac dissection].
AB  - Subacute left lower limb ischemia developed in a patient with aortic dissection.
      Angiography revealed a dissection of the aorta abdominalis and a severe stenosis
      of the left common iliac artery. The patient underwent successful percutaneous
      fenestration and intravascular stent placement. The patient is currently (4 month
      post-intervention) ambulating without any signs of the leg ischemia. Percutaneous
      balloon fenestration and, if necessary, stent placement should be considered as a
      treatment option and a alternative to surgery in selected cases.

PMID- 8533455
TI  - [Pseudological psychologism--a current manifestation].

PMID- 8533454
TI  - Radiation-induced vascular damage.
AB  - A 55-year-old male underwent detailed angiological and biochemical investigation
      because his daughter suffered from myocardial infarction in the 29th gestational
      week. An inborn familial plasma factor defect and increased Lp(a) were detected.
      Localized vascular changes were found in the right femoral artery while the
      resting vascular system was normal. Anamnestic data revealed a testicular cancer
      and therapeutic irradiation in that area (5000 rad) 12 years ago.

PMID- 8533456
TI  - Characterization of retrovirus-induced SC-1 cell fusion.
AB  - Virus-mediated cell-cell fusion with Moloney MLV and SC-1 cells was
      characterized. The level of fusion was highly dependent on the cell line used for
      propagation of the virus. Efficient fusion appeared to be very sensitive to
      negative charges on the cell surface and surroundings. Addition of polycations,
      removal of serum, and treatment with neuraminidase or hyaluronidase all
      stimulated fusion. Conversely, fusion was inhibited by fibronectin. Kinetic
      results and the time of action of inhibitors indicated that virus particles (or
      virus material) on the cell surface lead directly to fusion. The fusion then
      proceeded rapidly and required actin movement as shown by cytochalasin
      inhibition.

PMID- 8533457
TI  - Evaluation of rubella virus E2 and C proteins in protection against rubella virus
      in a mouse model.
AB  - An animal model is described that can provide further information for evaluating
      novel vaccines against rubella virus (RV). A group of mice was immunized with the
      lysate of insect cells infected by a recombinant baculovirus expressing E2 and C
      proteins of RV. Another group of mice was immunized with the RA27/3 rubella
      vaccine. After 2 weeks, both groups of mice were challenged intramuscularly with
      live RV and the blood was drawn after 8, 24, 48 and 72 h. The presence of rubella
      challenge virus in an unnatural host, such as the mouse, was monitored by RT-PCR.
      The mice immunized with the RA27/3 rubella vaccine were the only ones able to
      inhibit the challenge virus replication, E2 and C proteins, which alone are not
      sufficient to protect animals against RV, served as a negative control for a
      protective vaccine against RV that expresses E1 protein of RV.

PMID- 8533458
TI  - Transcriptional regulation of cellular and viral promoters by the hepatitis C
      virus core protein.
AB  - The genomic region encoding the hepatitis C virus (HCV) core protein was cloned
      into a mammalian expression vector to study its role on the transcriptional
      regulation of cellular proto-oncogene and viral promoters. Using a transient
      transfection assay in human hepatocellular carcinoma (HepG2) cells, we
      demonstrate that the HCV core protein activates the human c-myc, Rous sarcoma
      virus long terminal repeat (LTR), and simian virus 40 (SV40) early promoters; and
      suppresses the c-fos promoter and human immunodeficiency virus type 1 (HIV-1) LTR
      activity. The transcriptional regulation of cellular proto-oncogenes by the HCV
      core protein suggests possible involvement of the core protein in the
      deregulation of normal hepatocyte growth and hepatocarcinogenesis.

PMID- 8533460
TI  - Molecular relationships in infectious pancreatic necrosis virus.
AB  - Infectious pancreatic necrosis virus (IPNV), a Birnaviridae with a double
      stranded RNA genome of two segments, is an important aquatic pathogen. Previous
      characterizations of the RNA and polypeptide patterns of different IPNV isolates
      have uncovered a wide variety of electropherotypes. We used RNA fingerprinting
      analysis to study the quasispecies, heterogeneity, and rapid mutation
      characteristics of IPN viruses. Via cluster analysis of the RNA fingerprints,
      IPNV standard serotypes as well as T42G-, T24K- and T34G-related isolates were
      classified into 3 clusters corresponding to the AB, SP, and VR-299 serological
      types. The IPNV SP cluster represents a different evolutionary route from those
      of the AB and VR-299 clusters. The VR-299 clusters were separated into two
      groups, the T34G group were divided into two subgroups. The molecular
      relationships between these isolates can be correlated with the biological
      characteristics of these IPN viruses, for example, selective growth in EPC cells
      and adaptive replication at high temperatures.

PMID- 8533459
TI  - Antigenicity of the rabbit hemorrhagic disease virus studied by its reactivity
      with monoclonal antibodies.
AB  - A panel of anti-rabbit hemorrhagic disease virus (anti-RHDV) monoclonal
      antibodies was produced and characterized. The ability of the MAbs to recognize
      epitopes present on RHDV capsids, European brown hare syndrome virus capsids and
      RHDV subunits was determined. Preliminary results on the neutralizing capacity of
      the MAbs were obtained by in vivo protection experiments. The antigenic map of
      RHDV obtained by this study is consistent with the current models of the
      calicivirus structure.

PMID- 8533461
TI  - Labeling of surface proteins of herpes simplex virus type 1 using a modified
      biotin-streptavidin system.
AB  - Methods of labeling surface proteins on herpes simplex virus (HSV) which have
      minimal effect on the biological activity of the virus are useful for the study
      of both the localization and function(s) of surface proteins. The present work
      describes a procedure using a water-soluble biotin compound, sulfo-NHS-biotin,
      which is unable to penetrate biological membranes and reacts with primary amines
      in proteins. Labeled proteins were detected by binding of [125I]streptavidin.
      Specific reaction with surface proteins was shown in Western blots using
      antibodies against selected proteins in the envelope or in the tegument. Proteins
      susceptible to iodination were also biotinylated, but the efficiency of labeling
      varied from one protein to another. As a result of freezing and thawing of the
      virus, as well as the manipulations involved in Ficoll gradient purification,
      internal proteins were labeled. The infectivity of the virus was reduced by
      approximately 40% after biotinylation. Labeled viruses were visualized by
      fluorescein isothiocyanate-conjugated streptavidin, and seen as distinct spots on
      the surface of the cells.

PMID- 8533462
TI  - Capsid diversity in small round-structured viruses: molecular characterization of
      an antigenically distinct human enteric calicivirus.
AB  - Studies of antigenic variation between small round-structured viruses (SRSVs)
      using immune electron microscopy have revealed 3 antigenic types currently
      circulating in the UK represented by the strains SRSV/Bri/93/UK, SRSV/Sot/91/UK
      and SRSV/Mel/89/UK. Mel/89/UK RNA was isolated from a 1989 school outbreak of
      gastroenteritis. The 3'-terminal 3435 nucleotides (excluding the poly(A) tail)
      were determined by RT-PCR and cDNA sequencing, completing our molecular
      characterization of antigenically diverse SRSVs. Coding regions for the
      calicivirus RNA polymerase and capsid protein were found together with a 3' open
      reading frame of unknown function. The polymerase region was most highly
      conserved between Mel/89/UK and the other two SRSVs while the 3' open reading
      frame exhibited extreme variation. Phylogenetic analysis of SRSV capsids showed
      that Mel/89/UK differed significantly from Bri/93/UK and Sot/91/UK (62 and 39%
      identity, respectively) and was distinct from 6 other non-UK SRSVs that had been
      previously characterized. This was consistent with the designation of Mel/89/UK
      as a novel antigenic variant. Comparison of the capsid amino acid sequences of
      the 3 UK strains together with the antigenically distinct SRSV/Nor/68/US revealed
      a hypervariable region that could be surface-exposed and contain the SRSV
      antigenic determinants.

PMID- 8533463
TI  - Induction of apoptotic DNA fragmentation by the infection of vesicular stomatitis
      virus.
AB  - Vesicular stomatitis virus (VSV) induced apoptosis of infected HeLa cells.
      Fragmentation of chromosomal DNA into nucleosomal oligomers as well as a
      characteristic nuclear fragmentation were observed in the infected cells. The
      kinetics of the apoptotic response was determined in relation to viral
      multiplication and cytopathic effect. Comparison of these kinetics revealed that
      the production of progeny virus occurs at almost similar kinetics to that of the
      DNA fragmentation, so that viral multiplication is not interrupted by the
      apoptotic cell damage.

PMID- 8533464
TI  - Role of the pyrimidine-rich tract on the translation of 'chimeric' polio
      hepatitis A mRNAs with engineered 5'-terminal untranslated regions.
AB  - The 5'-terminal untranslated region (5'-UTR) of picornavirus RNA contains a
      series of cis-acting elements required for the internal initiation of
      translation, including a pyrimidine-rich tract (PRT), which in entero- and
      rhinoviruses is located about 20 nts upstream from a silent AUG triplet in the
      vicinity of the translation initiation site. In hepatitis A virus (HAV) RNA, the
      PRT is only 12 nts upstream from the legitimate AUG initiation codon, and a
      second, longer PRT in a region far removed from the translation initiation site.
      This 5'-distal PRT includes a 'core' sequence 80% homologous to the PRT of
      poliovirus RNA. A 'chimeric' polio-hepatitis A mRNA was constructed in which the
      sequences extending between nucleotides 45 and 156 of HAV RNA replaced the
      corresponding ones in poliovirus 5'-UTR. The construction was extended with
      poliovirus sequences up to position 1809. The recombinant mRNA so generated
      carried two copies of the PRT. In vitro translation in lysates of truncated
      poliovirus mRNAs generated a single peptide of Mr = 39 kDa, while the chimeric
      mRNA generated a series of short peptides as a result of fortuitous (or aberrant)
      initiation events. A more extensive substitution in the chimeric 5'-UTR which
      removed the 3'-most PRT brought by the poliovirus sequences, restored the
      translation at the authentic initiation site. Point mutations were engineered in
      the 5'-most PRT of the chimeras, and bi-cistronic plasmids were constructed in
      which either the parental poliovirus 5'-UTR or the chimeric ones were introduced
      in the intergenic region. Upon transfection of COS-1 cells, the chimeric polio
      hepatitis A 5'-UTR containing two PRTs did not express the reporter gene. Removal
      of the 3'-distal PRT or point mutations engineered into the 5'-most PRT partially
      restored the transient expression of the reporter gene, consistent with the
      notion that a single (and only a single) functionally active PRT in a proper
      context is required to secure the internal initiation of translation of bi
      cistronic mRNAs in vivo.

PMID- 8533465
TI  - Epitope mapping of cross-reactive monoclonal antibodies specific for the
      influenza A virus PA and PB2 polypeptides.
AB  - Characterization of the epitopes recognized by 21 monoclonal antibodies (MAbs)
      specific for the influenza A virus PA (13 MAbs) and PB2 (8 MAbs) polypeptides
      (Barcena et al. (1994) J. Virol. 68, 6900-6909) raised against denatured
      polypeptides produced in E. coli is described. MAbs were characterized by: (1)
      competitive binding ELISAs; (2) mapping of the protein regions that specify their
      binding sites; and (3) analyses of their ability to recognize the corresponding
      viral protein in a number of viral isolates. Five and three non-overlapping
      antigenic areas were defined by the anti-PA and anti-PB2 MAbs, respectively. Five
      of the anti-PA MAbs recognized antigenic determinants located within the amino
      terminal 157 amino acids of the PA protein, and 6 others reacted strongly with a
      PA fragment comprising the first 236 amino acids. All 8 anti-PB2 antibodies
      reacted strongly with a polypeptide fragment containing amino acids 1-113 of the
      PB2 protein. Analyses of the reactivities of 4 anti-P antibodies with 23
      influenza A virus reference strains isolated over a period of 61 years and
      recovered from humans, pigs, birds and horses, showed that the epitopes were
      conserved among all viral isolates. The application of these antibodies as
      research and diagnostic tools is discussed.

PMID- 8533466
TI  - Transcriptional studies on yeast SEC genes provide no evidence for regulation at
      the transcriptional level.
AB  - A number of proteins have been identified as components of the secretory pathway
      of Saccharomyces cerevisiae (SEC gene products). However, very little is known
      about the expression of these components and their regulation at the
      transcriptional level. In this study yeast cells were exposed to conditions that
      changed the secretory activity of the cells. The conditions analysed include the
      different stages of the cell cycle, overexpression of secretory proteins, and
      block of secretion and endocytosis. The effect of these conditions on the
      transcriptional expression levels of a number of SEC genes (SAR1, SEC1, SEC14,
      SEC17, SEC18, SEC23, SEC62, YPT1) was analysed. In summary, no major changes in
      transcriptional expression levels could be detected. From these results we
      conclude that the components of the secretory pathway are expressed
      constitutively and that no general regulation of transcription exists, that could
      adjust the expression level of the SEC genes to the secretory activity of the
      cells.

PMID- 8533467
TI  - Targeting of heterologous membrane proteins into proliferated internal membranes
      in Saccharomyces cerevisiae.
AB  - Overproduction of chimeric proteins containing the HMG2/1 peptide, which
      comprises the seven transmembrane domains of Saccharomyces cerevisiae 3-hydroxy-3
      methylglutaryl-CoA reductase isozymes 1 and 2, has previously been observed to
      induce the proliferation of internal endoplasmic reticulum-like membranes. In
      order to exploit this amplified membrane surface area for the accommodation of
      heterologous microsomal proteins, we fused sequences coding for human cytochrome
      P4501A1 (CYP1A1) to sequences encoding the HMG2/1 peptide and expressed the
      hybrid genes in yeast. The heterologous hybrid proteins were targeted into
      strongly proliferated membranes, as shown by electron microscopic and
      immunofluorescent analysis. Fusion proteins comprising the whole CYP1A1
      polypeptide (HMG2/1-CYP1A1) exhibited 7-ethoxyresorufin-O-deethylase activity,
      whereas fusion proteins lacking the N-terminal 56 amino acids of CYP1A1 (HMG2/1
      delta CYP1A1) were inactive and appeared to be unable to incorporate protoheme.
      Similar amounts of heterologous protein were detected in cells expressing HMG2/1
      CYP1A1, HMG2/1-delta CYP1A1 and CYP1A1, respectively. Replacement of the N
      terminal membrane anchor domain of human NADPH-cytochrome P450 oxidoreductase by
      the HMG2/1 peptide also resulted in a functional fusion enzyme, which was able to
      interact with HMG2/1-CYP1A1 and the yeast endogenous P450 enzyme lanosterol-14
      alpha-demethylase.

PMID- 8533468
TI  - Scp160p, a new yeast protein associated with the nuclear membrane and the
      endoplasmic reticulum, is necessary for maintenance of exact ploidy.
AB  - We have cloned a new gene, SCP160, from Saccharomyces cerevisiae, the deduced
      amino acid sequence of which does not exhibit overall similarity to any known
      yeast protein. A weak resemblance between the C-terminal part of the Scp160
      protein and regulatory subunits of cAMP-dependent protein kinases from eukaryotes
      as well as the pstB protein of Escherichia coli was observed. The SCP160 gene
      resides on the left arm of chromosome X and codes for a polypeptide of molecular
      weight around 160 kDa. By immunofluorescence microscopy the Scp160 protein
      appears to be localized to the nuclear envelope and to the endoplasmic reticulum
      (ER). However, no signal sequence or membrane-spanning region exists, suggesting
      that the Scp160 protein is attached to the cytoplasmic surface of the ER-nuclear
      envelope membranes. Disruption of the SCP160 gene is not lethal but results in
      cells of decreased viability, abnormal morphology and increased DNA content. This
      phenotype is not reversible by transformation with a plasmid carrying the wild
      type gene. Crosses of SCP160 deletion mutant strains among each other or with
      unrelated strains lead to irregular segregation of genetic markers. Taken
      together the data suggest that the Scp160 protein is required during cell
      division for faithful partitioning of the ER-nuclear envelope membranes which in
      S. cerevisiae enclose the duplicated chromosomes.

PMID- 8533469
TI  - Molecular cloning of the GTP-cyclohydrolase structural gene RIB1 of Pichia
      guilliermondii involved in riboflavin biosynthesis.
AB  - The structural gene of GTP-cyclohydrolase, involved in riboflavin biosynthesis,
      was cloned from a Pichia guilliermondii genomic library. A 1855 bp genomic DNA
      fragment complementing the riboflavin auxotrophies of an Escherichia coli ribA
      mutant, defective in GTP-cyclohydrolase II, and a P. guilliermondii rib1 mutant
      was isolated and sequenced. An open reading frame with the potential to encode a
      protein of 344 amino acids with a predicted molecular mass of 38,711 Da was
      detected. The P. guilliermondii enzyme shows a high degree of homology to GTP
      cyclohydrolases type II from E. coli and Baccillus subtilis and to GTP
      cyclohydrolase from Saccharomyces cerevisiae. Functional GTP-cyclohydrolase from
      P. guilliermondii may consist of four identical subunits.

PMID- 8533470
TI  - The effect of ethanol and specific growth rate on the lipid content and
      composition of Saccharomyces cerevisiae grown anaerobically in a chemostat.
AB  - The effects of produced ethanol and specific growth rate on the lipid content and
      composition of Saccharomyces cerevisiae CBS 2806 were studied using anaerobic
      chemostat cultures. The cells adapted to increased concentrations of produced
      ethanol by increasing the proportion of ergosterol at the expense of lanosterol,
      by increasing the proportion of phosphatidylinositol at the expense of
      phosphatidylcholine, and by increasing the amount of C18:0 fatty acids in total
      phospholipids at the expense of C16:0 fatty acids. The produced ethanol had no
      effect on the phospholipid content nor on the proportion of unsaturated fatty
      acids in the phospholipids. The specific growth rate had no effect on the
      phospholipid content, the sterol composition, the phospholipid composition, the
      fatty acid composition of total phospholipids, or on the proportion of
      unsaturated fatty acids in the phospholipids of S. cerevisiae. It was not
      possible to separate the effects of produced ethanol and growth rate on the
      ergosterol content of the chemostat-grown S. cerevisiae cells.

PMID- 8533471
TI  - New open reading frames, one of which is similar to the nifV gene of Azotobacter
      vinelandii, found on a 12.5 kbp fragment of chromosome IV of Saccharomyces
      cerevisiae.
AB  - The nucleotide sequence of a 12.5 kbp segment of the left arm of chromosome IV is
      described. Five open reading frames (ORFs) longer than 100 amino acids were
      detected, all of which are completely confined to the 12.5 kbp region. Two ORFs
      (D1271 and D1286) correspond to previously sequenced genes (PPH22 and VMA1 or
      TFP1, respectively). ORF D1298 shows the characteristics of alpha-isopropylmalate
      and homocitrate synthase genes and is similar to the nifV gene of Azotobacter
      vinelandii. Two more ORFs have no apparent homologue in the data libraries.
      Conversely, two smaller ORFs of 25 and 85 amino acids encoding the ribosomal
      protein YL41A and an ATPase inhibitor, respectively, were detected. Although a
      substantial part of the 12.5 kbp fragment apparently lacks protein-coding
      characteristics, no other elements, such as tRNA genes or transposons, were
      found.

PMID- 8533472
TI  - The sequence of a 44 420 bp fragment located on the left arm of chromosome XIV
      from Saccharomyces cerevisiae.
AB  - We have determined the complete nucleotide sequence of a 44 420 bp DNA fragment
      from chromosome XIV of Saccharomyces cerevisiae. The sequence data revealed 23
      open reading frames (ORFs) larger than 300 bp, covering 73.5% of the sequence.
      The ORFs N2418, N2428, N2441, N2474 and N2480 correspond to previously sequenced
      S. cerevisiae genes coding respectively for the mitochondrial import protein
      Mas5, the nucleolar protein Nop2, the outer mitochondrial membrane porin Por1,
      the cytochrome c oxidase polypeptide VA precursor CoxA and the yeast protein
      tyrosine phosphatase Msg5. Translation products of three other ORFs N2406, N2411
      and N2430 exhibit similarity to previously known S. cerevisiae proteins: the
      ribosomal protein YL9A, the protein Nca3 involved in the mitochondrial expression
      of subunits 6 and 8 of the ATP synthase and actin; in addition N2505 presents
      strong similarity to an ORF of chromosome IX. The predicted protein products of
      ORFs N2417 and N2403 present similarities with domains from proteins of other
      organisms: the Candida maltosa cycloheximide-resistance protein, the human
      interleukin enhancer-binding factor (ILF-2). The 12 remaining ORFs show no
      significant similarity to known proteins. In addition, we have detected a DNA
      region very similar to the yeast transposon Ty 1-15 of which insertion has
      disrupted a tRNA(Asp) gene.

PMID- 8533473
TI  - A 29.425 kb segment on the left arm of yeast chromosome XV contains more than
      twice as many unknown as known open reading frames.
AB  - The nucleotide sequence of a 29.425 kb fragment localized on the left arm of
      chromosome XV from Saccharomyces cerevisiae has been determined. The sequence
      contains 13 open reading frames (ORFs) of which four encode the known genes ADH1,
      COQ3, MSH2 and RCF4. Predictions are made concerning the functions of the unknown
      ORFs. Some of the ORFs contain sequences similar to expressed sequence tags (EST)
      found in the database made available by TIGR. In particular, the highly expressed
      ADH1 gene is represented in this database by no less than 20 EST sequences. Two
      ARS sequences and a putative functional GCN4 motif have also been detected. One
      ORF (O0953) containing nine putative transmembrane segments is similar to a
      hypothetical membrane protein of Arabidopsis thaliana. Characteristic features of
      the other ORFs include ATP/GTP binding sites, a fungal Zn(2)-Cys(6) binuclear
      centre, an endoplasmic reticulum targeting sequence, a beta-transducin repeat
      signature and in two instances, good similarity to the prokaryotic lipoprotein
      signal peptide motif.

PMID- 8533475
TI  - Current awareness on yeast.

PMID- 8533474
TI  - An 8.2 kb DNA segment from chromosome XIV carries the RPD3 and PAS8 genes as well
      as the Saccharomyces cerevisiae homologue of the thiamine-repressed nmt1 gene and
      a chromosome III-duplicated gene for a putative aryl-alcohol dehydrogenase.
AB  - A 8.2 kb DNA segment from the left arm of Saccharomyces cerevisiae chromosome XIV
      (GenBank/EMBL accession number: X83226) encompasses four open reading frames
      (ORFs) longer than 100 residues. The ORF N0295 is highly similar to the
      Aspergillus parasiticus and Schizosaccharomyces pombe nmt1 gene products, which
      are involved in thiamine biosynthesis and are strongly repressed by thiamine.
      N0300 is 76% identical to YCR107w, a hypothetical protein of yeast chromosome
      III, and 55% identical to a ligninolytic aryl-alcohol dehydrogenase from the
      white-rot fungus Phanerochaete chrysosporium. In addition, this fragment encodes
      Rpd3, a pleiotropic transcription factor (Vidal and Gaber, 1991), and part of
      Pas8, a protein essential for the biogenesis of peroxisomes (Voorn-Brouwer et
      al., 1993).

PMID- 8533476
TI  - [Fractures of the coxal femur end].

PMID- 8533477
TI  - [Classification, therapy and complications of pediatric femoral neck fractures].
AB  - Femoral neck fractures in children are rare injuries (less than 1 percent). The
      fracture pattern consists of transepiphyseal, transcervical, cervicotrochanteric
      and intertrochanteric fractures. Main problems with this type of injury are
      avascular necrosis, varus deformity, nonunion and premature epiphyseal closure.
      Varus and nonunion are affected by the treatment, vascular compromise with
      necrosis or growth problems are not related to therapy and hardly to control.
      Primary dislocated fractures are emergencies and need immediate operative
      management. Stabilization is achieved with K-wires or cancellous screws dependent
      on the child's age. In children below 3 years a pelvis cast is necessary post
      operatively. Partial weight bearing is started 6 weeks post trauma and is rapidly
      increased to full weight bearing. One year post-operation the metal is removed, K
      wires directly after bony healing.

PMID- 8533478
TI  - [Medial femoral neck fracture--femur head preserving therapeutic concepts].
AB  - Intracapsular femoral neck fractures of patients younger than 65 should be
      treated by open or closed reduction and internal fixation with two to four lag
      screws. Garden I fractures should also be treated by percutaneous screw fixation
      to prevent a delayed dislocation. If the fracture is dislocated (Garden II-IV)
      immediate reduction and internal fixation is mandatory to improve the blood flow
      by "unkinking" of the supporting vessels. The rate of femoral head necrosis is
      about ten to fifty percent, according to the grade of posttraumatic dislocation.
      Early stages of total or partial femoral head necrosis can be successfully
      treated by vascularized cortical bone grafts. In our institute a graft
      vascularized by the quadratus femoris muscle is preferred. Valgisation osteotomy,
      alloarthroplasties and arthrodeses in very young people are performed in cases of
      irreversible total femoral head necrosis.

PMID- 8533479
TI  - [Femoral neck fracture in the elderly--differential procedure].
AB  - Recent investigations and new devices allow specific regimens in the management
      of dislocated femoral neck fractures. Very old, immobile patients with a bad
      prognosis should be treated with a femoral head prosthesis. Patients with either
      arthritis, osteopenia, dysplasia or rheumatoid arthritis should receive a total
      hip prosthesis. The remaining population (age > 65 years) with dislocated femoral
      neck fractures and intact acetabulum should be managed with a bipolar
      hemialloarthroplasty. The protrusion rate is not significant.

PMID- 8533480
TI  - [Management of ipsilateral fractures of the femur shaft and proximal femur-
      therapy overview and current management].
AB  - Fractures of the femoral shaft are combined in 2-5% of all cases with an
      ipsilateral fracture of the proximal femur. These double fractures are mostly
      caused by high energy trauma. An analysis of 9 selected papers points to the
      problem. In more than 10% the proximal fracture is not diagnosed initially. In
      the literature nearly 30 different operative treatments are described and
      underline the demands on proper operative techniques and implants for ipsilateral
      femoral shaft and hip fractures. In this publication the new unreamed femoral
      nail system (UFN) with a special proximal interlocking option for double
      fractures will be presented. This system provides a good possibility to stabilize
      femoral double fractures in an easy and safe manner.

PMID- 8533481
TI  - [Pertrochanteric fractures].
AB  - Pertrochanteric fractures ordinary appear to women 10 to 15 years later than to
      men. Only 49 per cent of the women and 63 per cent of the men have a good bone
      structure at that time according to the Singh-index. The classification of
      pertrochanteric fractures follows the proposal of the AO-ASIF Group. The force
      which works at the hip joint depends on the function of the limb and is mainly
      caused by the musculature. This force exceeds up to 4.5 times the body weight.
      The first 6-24 hours after trauma are the optimal moment for operation.
      Anaesthesia methods near by the spinal cord should be preferred. The mainly used
      implant in Germany is the Dynamic Hip Screw (DHS) in more than 60 per cent of
      cases. Intramedullary implants only reach 15.5 per cent. A fracture table is
      dispensable for the implantation of a DHS, but the additional fixation of the
      greater trochanter and in some cases also the lesser trochanter is important. The
      Gamma Nail is prone to complications caused by the operation. A total hip
      arthroplasty is performed in about 10 per cent of all pertrochanteric fractures.
      The AO-document-center can show, that arthroplasty gives very good long-term
      results. The 130 degrees blade-plate and the Ender-Nail are only used in
      individual cases. 20 per cent of the patients must have an intensive care follow
      up treatment during a medium hospital stay of 29 days, 21 per cent have general
      non-surgical complications and 8 per cent of the patients die. Nevertheless 78
      per cent of all patients can be discharged under partial or full weight-bearing.
      Scores which allow a comparison of the pre- and postoperative functional status
      must be applied in order to compare different methods of hip fracture treatment.
      In a follow-up study 2.7 years after the accident 54 of our own patients had a
      medium reduction in their functional status of 10 to 15 per cent compared pre-
      and postoperatively.

PMID- 8533482
TI  - [Pathological fractures of the proximal femur end].
AB  - Bone metastases are located most frequently in cancellous bone according to the
      higher blood perfusion rate. In contrast, pathological fractures are most
      frequently found in the biomechanically highest loaded parts of the skeleton and
      are therefore most frequent in the proximal femur end. For definition of
      impending pathological fracture the Mirels Score should be used today. Because of
      the short life expectancy of the patients with pathological fractures caused by
      bone metastases immediate pain relief, function and weight bearing capacity must
      be achieved. In the proximal femur stabilisation can be performed with a hip
      tumor prosthesis or, as joint preserving device, a double plate compound
      osteosynthesis (DPCO). The results of 30 patients treated with hip tumor
      prosthesis and 30 patients treated with a DPCO of the proximal femur between 1985
      1989 were compared. The local complication rate of the tumor prosthesis was
      significantly higher (16.6% vs 46.6%) due to 11 hip luxations seen in 7 of the 30
      patients. The time of hospitalisation as well as the costs of the device are
      higher for the tumor prosthesis. The functional and subjective results were
      similar. Only in patients with very advanced carcinoma and a life expectancy
      under 3 months osteosynthesis without resection of the metastasis should be
      performed. For this indication only locked nail systems should be used today. We
      found the best functional results among 134 patients treated between 1982-1989 in
      our hospital in patients with impending pathological fractures. The functional
      results as well as the survival time were up to 3 times superior to those of
      patients with occurred pathological fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533483
TI  - [Various possibilities for managing subtrochanteric fractures].
AB  - Subtrochanteric fractures are highly unstable. For treatment, open reduction and
      internal fixation are the method of choice. The 95 degrees condylar plate is
      widely used for stabilization of these fractures. Alternative devices are the
      gamma nail and the recently developed intramedullar nail with a twisted plate
      which allows immediate postoperative weight bearing. The reported complications
      of the gamma nail restrict its general application, whereas preliminary reports
      of the intramedullar nail with the twisted plate are encouraging. Further
      clinical data are necessary before its general application can be recommended.

PMID- 8533484
TI  - [Diagnosis and therapy of local infections after surgical management of proximal
      femoral fractures].
AB  - Postoperative infections after trochanteric and intracapsular hip fractures are
      rare. Critical clinical observation of the wound during the early postoperative
      period and the evaluation by sonography as well as the determination of the C
      reactive protein are important factors in the diagnosis of early haematoma and
      wound infections. If revision surgery of suspected infections is immediately
      performed, good long-term results are to be expected. Infected
      hemialloarthroplasties and loosened total hip arthroplasties (THR) should be
      retrieved. If a mild infection is present, one stage revision arthroplasty is
      indicated. In case of gram-negative infections, however, alloarthroplasties
      should be removed and the total hip replacement should be delayed for 3 to 6
      months.

PMID- 8533485
TI  - [Surgical management of complications of open pelvic injuries].
AB  - Open pelvic fractures are rare fractures usually resulting from a severe trauma.
      Only 4 of 121 patients treated operatively in 1994 for a pelvic trauma showed an
      open injury. The high lethality is caused by two complications: in the early
      phase the patient is threatened by bleeding to death and in the following course
      sepsis determines the lethal outcome. Only an aggressive surgical management
      prevents or treats such complications. The presented concept comprises in the end
      the hemipelvectomy and an intensive care management for prophylaxis of septic
      complications. So the lethality was diminished.

PMID- 8533486
TI  - [Long-term outcome after conservative treatment of pelvic ring injuries and
      conclusions for current management].
AB  - Until the early eighties conservative treatment was common even for unstable
      pelvic fractures. The long-term results of 114 non-operatively treated patients
      who had suffered a pelvic fracture (68 type A, 20 type B, 26 type C according to
      the classification of the ASIF) have been examined after an average time of 7.1
      years after injury. 60% of cases with a stable injury of the pelvis (type A) did
      not suffer of any complaint. The remaining patients stated moderate pain. After
      conservative treatment of type B pelvic injuries 55% complained of pain or showed
      an impaired functional result. Former vertical-shear fractures (type C) showed
      worse results than type B pelvic injuries: only 15% did not suffer of any pain
      and 10% had no functional deficit. Patients with unstable pelvic fracture
      localized pain mainly in the lumbo- or iliosacral region. Radiological and CT
      findings suggest arthrosis, partial ancylosis and incomplete reduction of the
      fracture as possible reasons for unsatisfactory clinical results. As consequence
      of these results we nowadays proceed extended radiological examinations (a.-p.-,
      inlet-, outlet-views, CT) and operative reduction and internal stabilization
      (ORIF) of all unstable pelvic fractures.

PMID- 8533487
TI  - [Threatened fibula fracture by transosseous migration of a leaded glass
      fragment].
AB  - A case of a 24-year-old man is reported: At the age of ten he was injured by a
      pane of glass in the region of the medial ankle joint. 14 years later a piece of
      broken glass which was overlooked during wound toilet, had penetrated to the
      lateral ankle. The foreign body was impacted in the distal fibula which was
      sensitive to pressure. Our case shows the importance of a careful inspection of
      every wound. An unrecognized foreign body may cause severe complications later
      on.

PMID- 8533488
TI  - [From the history of surgical instruments: 3. The dressing forceps (16th
      century)].
AB  - The dressing forceps ("Kornzange") is one of the very few surgical instruments
      that have extensively preserved its form, its function and even its name
      throughout the centuries. In the Germany of the 16th century, the dressing
      forceps was mentioned as a widely used instrument among the barber-surgeons
      (Stromayr 1559, Ryff 1559). At that time, it mostly found use as a foreign body
      removing forceps. The dressing forceps can be traced back until today in German
      or English surgery instrument-books in nearly unchanged shape.

PMID- 8533489
TI  - Advances in oral hormonal contraception.

PMID- 8533490
TI  - [Interferon-alpha controls HPV infection in cervix epithelium].
AB  - Decreased immune response is necessary for a prolonged HPV-infection and allows
      HPV to be virulent as an oncogene. This study shows that HPV-infection in
      cervical epithelium is determined by the immune system and IFN-alpha can be shown
      to be a prognostic parameter for the HPV-infection. The cytokines (IFN-alpha, IFN
      gamma, and TNF-alpha) from stimulated peripheral blood mononuclear cells (PBMC)
      were measured using monoclonal IFN-antibodies and ELISA test. To detect HPV-16,
      PCR (e6 and e7 areas) was used, followed by southern-blot of the PCR-products. In
      all of our patients (n = 139) no cytological change was observed in the cervical
      epithelium over a period of 3 years. Comparison was made between 3 groups: 1:
      controls (n = 89, HPV-pos. n = 6) 2: registered prostitutes without drug abuse (n
      = 30, HPV-pos. n = 6) and 3: HIV-infected, previous drug users (CDC II, n = 20,
      HPV-pos. n = 2). RESULTS: The stimulated IFN-alpha values are highest in the
      control collective (169 +/- 35 U/ml) and are significantly lower in the
      prostitutes (98 +/- 26 U/ml, p < 0.05) and in the HIV-infected group (49 +/- 15
      U/ml, p < 0.01). The difference between the latter groups being significant as
      well (p < 0.05). Dividing the controls into HPV-16 positive and HPV-16 negative
      subgroups, the IFN-alpha values are significantly higher in HPV-16 negative group
      (193 +/- 48 U/ml) compared to HPV-16 positive group (38 +/- 3 U/ml, p < 0.05).
      Also in the collective of prostitutes and HIV infected patients there is a
      similar significant difference between the HPV-16 positive and HPV-16 negative
      patients (Prostitutes: HPV-16 negative = 94 +/- 21 U/ml, HPV-16 positive = 36 +/-
      7 U/ml, p < 0.05; HIV-infected: HPV-16 negative = 35 +/- 13 U/ml, HPV-16 positive
      = 13 +/- 3 U/ml).

PMID- 8533491
TI  - [Diagnosis and therapy of toxoplasmosis infections in pregnancy at the Rostock
      University Gynecologic Clinic 1986-1994].
AB  - Over a period of eight years, 61 patients with toxoplasmosis infection in
      pregnancy were examined retrospectively at women's hospital. Diagnosis of
      maternal infection was based on seroconversion, positive IgM, raising IgG--titers
      above twofold, and very high primary titers in SFT. In 20 patients (32.8%)
      diagnosis was found with seroconversion. In 15 patients (24.6%) the first
      examination revealed very high titers (SFT > or = 1:2000, KBR > or + 1:40)> Using
      a score, time of infection was grouped into: periconceptional (24.59%), 1st
      Trimester (34.43%) 2nd Trimester (31.14%), 3rd Trimester (4.92%), not specified
      (4.92%). The latency phase between first suspect titer and treatment did vary
      markedly. Duration of latency phase was longer than 6 weeks only in 10% and 20%
      of cases identified via seroconversion or very high titers respectively. Of all
      cases with different diagnostic attempts 73.9% were treated later than 6 weeks
      after the first suspect titer. Therapy was performed with either a combination of
      pyrimethamine-sulfadiacine or spiramycin monotherapy. In 18/53 newborns (33.9%)
      fetal infections were proven with IgM-detection post partum. Clinical evaluation
      was normal in 48 children (77.5%). 6 newborns (9.7%) had dilated cerebral
      ventricles; 3 (4.8%) had irregularly dense intracerebral structures, one newborn
      (1.6%) had intracerebral calcifications. Primary neurological check-up of the
      newborn was normal in 91.9%. 2 children (3.2%) had facial paralysis or reduced
      muscle tonus. In 2 newborns (3.2%) opthalmological examination of the fundus
      revealed signs of retino-chorioditis.

PMID- 8533492
TI  - [Laparoscopy-assisted vaginal hysterectomy (LAVH)--a comparison between vaginal
      and abdominal hysterectomy with reference to intra- and postoperative quality
      parameters].
AB  - First experiences after the introduction of LAVH with regard to intra- and
      postoperative parameters of quality in comparison with the classical abdominal
      and vaginal hysterectomies are shown. The main indications for LAVH were large
      myomas, previous pelvic surgery and adnexal mass. Intra- and postoperative
      complications, time of operation, uterine weight, estimated blood loss, the
      period of use of analgetics and discharge wishes of 40 patients after abdominal
      and 25 after vaginal hysterectomies were compared with the results of 30 patients
      after LAVH. Patients after abdominal hysterectomy need more and longer
      analgetics. The lowest perioperative morbidity we found in the LAVH group. In
      cases with enlarged uteri the high blood loss during the vaginal hysterectomy can
      be significantly reduced with LAVH. LAVH offers a new technique to convert a lot
      of abdominal hysterectomies with benign indications (large myomas, adhesions,
      adnexal mass) into vaginal hysterectomies.

PMID- 8533493
TI  - [Atrial natriuretic peptide in normotensive pregnancy: concentrations in physical
      stress, pre- and postpartal and in the umbilical cord].
AB  - The concentrations of the atrial natriuretic peptide (ANP) during the 3rd
      trimester of pregnancy (n = 54), the 1st, 2nd, and 3rd day post partum and in 10
      non pregnant females were measured and compared. Moreover ANP was determined in
      the umbilical cord (artery n = 10, vein n = 48) and the influence of exercise on
      the concentration of ANP in pregnant (n = 10) and non pregnant women (n = 10) was
      analyzed. There was no significant difference of the ANP-values measured in non
      pregnant patients and during the third trimester (100 +/- 57 vs. 97 +/- 27
      pg/ml). On the 3rd day post partum a significant rise of ANP was noted (1st day
      post partum 78 +/- 43, 3rd day post partum 102 +/- 46, 5th day post partum 84 +/-
      40 pg/ml). During physical exercise the concentration of ANP increases
      significantly in pregnant (103 +/- 45 vs. 120 +/- 57 pg/ml, p < 0.05) as well as
      in non pregnant females (97 +/- 27 vs. 111 +/- 39 pg/ml, p < 0.05). In arterial
      blood samples from the umbilical cord the concentration of ANP was higher than in
      venous cord blood (62 +/- 34 vs. 51 +/- 28 pg/ml, p > 0.05).

PMID- 8533494
TI  - [General perioperative prevention of thromboembolism in gynecology with low
      molecular weight heparin: clinical experiences with enoxaparin over 7 years].
AB  - We report on clinical experiences with a low molecular weight heparin
      (Enoxaparin). Altogether 2339 patients undergoing gynecologic surgery received 20
      or 40 mg Enoxaparin once a day beginning 2 hours before surgery. The dose was
      chosen depending on an assessment of the individual risk factors for each
      patient. No deep venous thrombosis and no pulmonary embolism were observed. Major
      intra- or postoperative bleeding was rare (0.3%). We considered these results as
      favorable. However, early physical therapy and mobilisation of the patients may
      present an important factor. Most importantly, dose adjustment according to
      individual risk assessment appears to be a very effective concept with respect to
      clinical management in gynecologic surgery.

PMID- 8533495
TI  - [Megalourethra caused by coitus].
AB  - Megalourethra due to urethral coitus is a very rare phenomenon in women. Anatomy,
      pathology and clinic are discussed.

PMID- 8533496
TI  - [Spontaneous abortion of one twin and later spontaneous delivery of the surviving
      twin].
AB  - The authors report a case of a diamnial-dictorial pregnancy with spontaneous
      abortion of the first foetus and late spontaneous delivery of the second twin.
      The intra-uterine death of the first foetus was diagnosed by sonography in the
      16th week of pregnancy. The intra-uterine development of the second twin was
      normal and the spontaneous delivery was in the 32. week of gestation. As
      conclusion the authors recommend diagnosis of twin pregnancy with distinction
      between monochorial and dictorial placenta should be made by sonography as early
      as possible.

PMID- 8533497
TI  - [Modified endocervical vaginal smear for diagnosis of endocervical microinvasive
      cervix carcinoma].
AB  - We report about a case of a highly intracervical located microcarcinoma of the
      cervix uteri, which could solely be diagnosed by a sufficient sampling technique
      using cyto-brush. The same case could not be diagnosed without the presence of
      endocervical cells in the endocervical smear either.

PMID- 8533498
TI  - [The problem of the frequent hospitalizations of the mentally ill].

PMID- 8533499
TI  - [Peripheral autonomic nervous system function in patients with hypothalamic
      insufficiency].
AB  - Peripheral vegetative nervous system state was estimated in 61 patients with
      constitutional acquired hypothalamic insufficiency by using non-invasive methods.
      Control group consisted of 10 healthy individuals. Cardiovascular tests
      application led to the evaluation of subclinical parasympathetic vegetative
      insufficiency. In was more prominent in patients with early neuroendocrine
      disorders debut as well as in those with more protracted disease durations. The
      authors suggest that these findings testify the constitutional acquired character
      of disturbances. Besides it was also found the conductivity velocity fall in
      sudomotor preganglionic fibers in arms and legs and the prevalence of such
      disorders in patients with expressed dysraphic status. The last observation may
      testify the defect in laying of these peripheral vegetative fibers. The study
      carried out permits to suppose that subclinical peripheral insufficiency occur to
      be one of the factors evoking rise either of permanent (tachycardia, arterial
      pressure elevation, hyperhidrosis) or of paroxysmal vegetative disturbances
      (panic attacks, migraine) in patients with hypothalamic insufficiency.

PMID- 8533500
TI  - [The clinical picture, diagnosis and therapy of headaches in patients with a
      hypothalamic syndrome].
AB  - 190 patients with hypothalamic insufficiency were investigated. The character,
      frequency of various forms of headache as well as its correlation with
      neuroendocrine emotional motivation and vegetative disorders were analysed. It
      was found that headache occurred more frequently in patients with hypothalamic
      insufficiency (66%) than in the whole population (5-20%). This confirms the role
      of diencephalic disfunction in its genesis. Psychovegetative disturbances were
      expressed most of all in tension-type headache (TTH). Very likely that some
      psychoendocrine mechanisms (particularly depression and idiopathic edema) play
      important role in pathogenesis of TTH. Clinical effect of Lerivon confirms the
      pathogenetic role of depression in these cases.

PMID- 8533501
TI  - [Psychoautonomic and neurovascular disorders in patients with autonomic vascular
      dystonia and the hyperventilation syndrome and methods for their correction].
AB  - 35 patients with vegetocirculatory dystonia and hyperventilation syndrome, but
      without the signs of organic lesion of nervous system were treated. The complex
      treatment included the breathing exercises with feedback mechanisms, the
      correction of psychovegetative and neurovascular disturbances, the massage of
      neck region and a head, psychotherapy, angioprotective, vegeto- and psychotropic
      drug therapy. The disappearance of acute vascular attacks and paroxysms of
      migrainous headache, the normalization of all breathing parameters and the
      improvement of vegetative status were observed in all patients.

PMID- 8533502
TI  - [The characteristics of the autonomic regulation of the heart rhythm in patients
      with the obstructive sleep apnea syndrome].
AB  - 15 patients with polysomnographically verified syndrome of obstructive apnoea in
      sleep (apnoea index value was equal to 35.6) were examined. The peculiarities of
      cardiac rhythm vegetative regulation were investigated with the help of
      cardiorhythmintervalography technique. The decrease of amplitude of the middle
      frequency peak (the slow waves of the first order, SW1) as well as the
      predominance of the low-frequency peak (slow waves of the second order, SW2) were
      observed in cardiac rhythm spectrum. These findings reflected the insufficiency
      in sympathetic-adrenal mechanisms of regulation. Besides, unlike the healthy
      individuals SW2 peak in patients exceeded significantly respiratory waves peak.
      The last observation combined with the weak influence of respiratory waves on the
      total rhythm dispersion was estimated as the initial parasympathetic regulation
      insufficiency manifestation.

PMID- 8533503
TI  - [The autonomic regulation of the cardiovascular system in subjects with the
      autonomic dystonia syndrome subjected to ionizing radiation exposure as a result
      of the accident at the Chernobyl Atomic Electric Power Station].
AB  - 180 males in the age of 21-50, all the participants of Chernobyl accident
      consequences liquidation were examined. In all individuals vegetative dystonia
      (VD) syndrome was diagnosed (total radiation doses 0.1-1.0 Grey according to D.
      Erwin method). It was established that VD syndrome differed in these persons by
      pronounced stages of disorders manifestation as well as by polymorphism of
      vegetative disturbances. These findings testify central and peripheral vegetative
      nervous system parts involvement. In 40.2% of cases in individuals which were
      examined in rest and in 56.2% after dosed physical loading the functional
      disorders of vegetative cardiovascular system regulation of vagal type mainly
      (76.5%) were revealed. Clear correlation was not observed between vegetative
      disorders and radiation dose value. The estimation of contribution of each of the
      possible pathogenic factors (exactly stressogenic, radioactive and others) in
      vegetative disturbances development is not possible now.

PMID- 8533504
TI  - [The dependence of the parasympathetic reaction of the mesencephalic section of
      the brain stem to age-, sex- and pigment-reagent-related factors].
AB  - Photoelectron pupillograph measurements of pupillary responses to light were made
      in 198 healthy individuals. Photoreaction of the pupils was declining with age
      contrary to the reciprocity rate which was stable (3.01-3.56). It indicates on
      the relative stability of parasympathetic-sympathetic relations. Young males with
      hyperpigmented irises had hyperactive parasympathetic reaction which sharply
      decreased to normal values at the age of 26-30 years. Estimated standard values
      of time, strength and speed of pupillomotor reaction can be used for comparative
      evaluation of autonomic neuromotor and brain structures involvement in various
      neurological diseases. These values may serve as initial point for devising
      medical algorithms and computer programs.

PMID- 8533505
TI  - [Panic attacks in wakening and during sleep].
AB  - The aim of this investigation was to determine the role of functional brain state
      in mechanisms of symptom formation of panic attacks (PA). The clinical and
      electrophysiological peculiarities of PA connected with their arising in
      different phases of awakening-sleep cycle were examined in 24 patients.
      Examination analysis resulted in revelation of some peculiarities in patients
      with PA of sleep, PA of awakening and PA of sleep and awakening. So the increase
      of cerebral as well as vegetative activation in patients with PA of sleep and PA
      of sleep and awakening in relaxed awakening state was observed while in patients
      with PA of awakening these changes were found during loading probes. The sleep
      alterations also presented such as diminution of sleep duration, increase of
      latent periods and decrease of total delta-sleep duration in patients with PA of
      sleep and with PA of sleep and awakening.

PMID- 8533506
TI  - [The clinico-electromyographic characteristics of spastic torticollis].
AB  - The aim of the study was the investigation of central and peripheral pathogenetic
      mechanisms of torticollis spasmodic. It was examined 68 patients-37 with left
      pathology and 31-with right one. Electromyograms (EMG) were registered in m.
      sternocleidomastoideus at rest and under postural loadings (at sitting and lying
      position of patients). Statistically significant differences were found in the
      pattern of EMG in connection of the side of torticollis. In the case of the left
      side of pathology EMG changes were presumably in "participating" muscle, in the
      right disorders-in "participating" muscle as well as in "nonparticipating" one
      (this change can be compensatory reaction which direct to the correction of a
      torsion).

PMID- 8533507
TI  - [The course of disseminated sclerosis in men and women].
AB  - It is known that a prevalence of multiple sclerosis in women is greater than in
      men (gender ration 2:1). The aim of the study was the analysis of sex differences
      in the course of disease. On the basis of clinical and paraclinical data,
      including data concerning mental state of patients emotional disturbances,
      intellectual functioning the authors determined that the development of multiple
      sclerosis in men is atypical as compare as women. In men the disease begins
      earlier and its course is more malignant, without remissions and efficacy of
      hormonotherapy. The data were interpreted as indicating the importance of the
      gender factor in the pathogenesis of disease.

PMID- 8533508
TI  - [The effect of aspirin on the contingent negative wave in healthy subjects].
AB  - Alterations in parameters of slow brain potentials (contingent negative
      variation, CNV) were examined in healthy individuals under influence of aspirin
      according to double blind method. The early and late waves of CNV were analysed.
      The significant decrease of early wave of CNV was obtained after aspirin
      administration. Late wave of CNV increased after aspirin and placebo intake. The
      alterations described were explained in terms of central mechanisms of aspirin
      action including noradrenergic and dopaminergic systems involvement.

PMID- 8533509
TI  - [The psychopathology of endogenous apathetic depressions].
AB  - The author examined 60 patients with manic-depressive psychosis and
      schizophrenia. In all cases the apathetic depression was observed in the
      psychopathological structure of these psychoses. On the basis of clinical
      analysis 3 types of apathetic depression were differentiated: simple apathetic
      (24 patients), apatho-melancholic (17 patients) and apatho-adynamic (19 patients)
      depression. The clinical picture of each of these types of apathetic depression
      was highly heterogeneous according to affective disturbances, different symptoms
      combinations and severity of disorder.

PMID- 8533510
TI  - [Melatonin excretion in patients with depression under the action of light of
      increased intensity].
AB  - The effects of 1 and 10 bright light exposures (2600-8000 lux) on melatonin
      excretion in patients with melancholic and anxious depressions were examined.
      Before treatment the increased basic levels of melatonin excretion were observed
      in patients with anxious depression. Melatonin excretion had been gradually
      normalized after 1 and 10 sessions of light therapy. The basic melatonin
      excretion in melancholic depressed patients was low and hadn't been changed after
      light therapy. Long term effects of light therapy depend upon the initial levels
      of melatonin excretion: low pretreatment levels increased and high pretreatment
      levels decreased after the therapy. The authors proposed that bright light
      exposures stimulated the restoration of adaptive function of pineal gland in
      depressed patients.

PMID- 8533511
TI  - [The thrombocytic serotoninergic markers of the efficacy of electroconvulsive
      therapy in endogenous depressions].
AB  - The changes of main platelet serotonergic parameters (maximal velocity of 3H
      serotonin uptake, Vmax; and density of (3)3H-imipramine binding sites, Bmax) were
      followed up in 25 endogenously depressed patients before and after
      electroconvulsive therapy (ECT). It was found a marked decrease in the velocity
      of 3H-serotonin uptake into platelets (Vmax) from patients before ECT (especially
      in non-responder group) and the significant increase of Vmax- and Bmax-values
      after the course of ECT in responders but not in resistant patients (non
      responders). The increase of Vmax- and Bmax-values in responders was evidence of
      the rise of the functional activity serotonin system after treatment. The results
      evidence about the significance of serotonergic-mechanisms in the therapeutic
      efficacy of ECT.

PMID- 8533512
TI  - [The fatty acid composition of the phospholipids of the erythrocyte membranes,
      thrombocytes and alpha-lipoproteins in schizophrenia patients].
AB  - 19 patients with different forms of schizophrenia as well as 10 healthy
      individuals and 6 alcoholic patients as a controls were examined. In was found
      that the fatty acid composition of phospholipids from schizophrenic patients
      erythrocytes membranes and platelets was not differed from control groups except
      the continuous sluggish schizophrenic patients. The decrease of polyunsaturated
      fatty acids C 20:3 (w = 9) and the increase C 20:5 (w = 6) were observed in the
      last case. The decrease of linoleic acid and C 20:5 (w = 3) acids levels in
      phospholipids of alpha-lipoprotein fraction was observed in all patients
      independently of their nosological form. The author suggests that last finding is
      the possible cause of the fatty acids deficiency chronization in brain
      structures.

PMID- 8533513
TI  - [The clinico-pathogenetic correlations in schizophrenia in adolescents and young
      people with a course of psychopathic-like disorders].
AB  - The influence of heredity and of premorbid personal peculiarities on the
      psychopathic-like disorders development in schizophrenic patients of adolescent
      juvenile age was analysed. Psychopathic-like disturbances were divided into 2
      groups exactly with either positive (type I) or negative or type II symptoms
      predominance in a whole clinical pattern. Symptoms mentioned above were observed
      in 47 and 53 patients respectively. As well as probands 216 relatives in the
      range of 1-3 degree of relation were examined too. It was revealed that in
      patients with type I of disorders schizophrenia debuted in adolescent-juvenile
      age meanwhile in type II it started in childhood. More severe hereditary loading
      in the form of various psychic pathologies took place in the case type I patients
      as compared with type II. Schizotype and hyperthymic personality characteristics
      prevailed in the first case, just as dissociated and passive features presented
      in type II.

PMID- 8533514
TI  - [The social psychological adaptation of patients with borderline mental
      disorders].
AB  - Social Interview Scale (SIS) elaborated by A. Clare and V. Cairns was applied.
      The principal information concerning adaptation and reliability of the method was
      presented. Two groups of patients with borderline disorders and control group
      (120 cases at all) were examined. The patient's groups were distinguished by the
      severity of the illness: the 1-st group included 30 continuous sluggish
      schizophrenic patients with pseudoneurotic symptoms (ICD-10: F 21) registered in
      mental health dispensary, the 2-nd group consisted of 50 neurotic patients who
      attended a psychiatrist in a district out-patient clinic (ICD-10: F 4). Social
      adaptation was estimated in terms of the basic areas of the man's life:
      housekeeping, professional occupation, material conditions, entertainments and
      leisure, microsocial relationships, matrimonial and family relations. It was
      found that schizophrenic patients were characterized first of all by severe
      complications in the interpersonal relations exactly with close relatives and in
      matrimonial sphere. Meanwhile neurotic patients were preoccupied mainly by social
      functioning problems as well as by job or housewife role dissatisfaction.

PMID- 8533515
TI  - [The medicosocial status of the victims of burns as a consequence of a suicide
      attempt (cases of self-immolation)].
AB  - 75 occasions of suicide attempts carried out by self-burning were analysed. It
      was revealed that the individuals in the age of 40-49 (unemployed and disabled)
      as well as physically working people predominated in most cases. Suicides were
      usually performed out of working sphere. In more than 70% of occasions either
      alcohol intoxication or some psychic diseases (which did not combine in one
      person) accompanied this kind of injury. No sex prevalence was observed in this
      group of patients.

PMID- 8533516
TI  - [The use of the Drionic apparatus for treating essential hyperhidrosis].
AB  - 40 patients with essential hyperhidrosis of palms, feet and axillary spaces were
      examined. All patients were divided into 2 groups: with permanent or remittent
      manifestations of hyperhidrosis. The prolongation of latent periods as well as
      the decrease of evoked skin sympathetic potentials amplitudes was observed in
      group with permanent type of hyperhidrosis as compared with remittent type
      patients or with control individuals. All patients were treated with "Drionic"
      apparatus (General Medical Co, USA) which therapeutic effect was based on water
      ionophoresis action. The decrease of sweating was demonstrated in 82.5% of cases.
      The treatment of palms and feet hyperhidrosis was more effective than of axillary
      spaces. The therapeutic effect in permanent group was better than in remittent
      group of patients. The investigation of evoked skin sympathetic potentials before
      the treatment resulted in the conclusion about high prognostic significance of
      potentials in curative effects of "Drionic" device.

PMID- 8533517
TI  - [The use of a decoction of the rhizome of Leuzea carthamoides for the treatment
      of alcoholics with depressive states].
AB  - Decoction of Leuzea carthamoides rhizome was prescribed inside (half glass, 4-5
      times a day during 2 months). The group of 37 patients was treated in ambulant
      clinic. From 28 patients who completed the treatment the remission which
      protracted up to 2 years was observed in 9 individuals, up to 1 year--in 11 and
      up to 6 months--in 8 persons. Decoction promoted correction not only depressive
      manifestations but also gastrointestinal diseases in some somatic patients. For
      alcoholic patients author recommends to use Leuzea carthamoides in combination
      with the another methods of therapy of alcoholism. Patients beard decoction
      administration well and hadn't suffered from any complications.

PMID- 8533518
TI  - [Idiopathic orthostatic hypotension (the Bradbury-Eggleston syndrome)].
AB  - The case of idiopathic orthostatic hypotension (Bradbury-Eggleston syndrome)
      which gradually arose in 70-years-old women was described. The clinical pattern
      of syndrome included pronounced orthostatic hypotension, fixed constant rare
      pulse (46-56 per minutes), independent of the changes in body position together
      with hypohidrosis and constipation. Autonomic nervous system investigation
      carried out with the help of the cardiovascular tests, spectral analysis of heart
      rhythm as well as sympathetic skin potential revealed expressed disturbances in
      autonomic functions of cardiovascular and sudomotor systems. Peculiarity of the
      case was the development of disease on the background of drug-compensated
      hypothyreosis which was not however the cause of progressive autonomic disorders
      in patient.

PMID- 8533519
TI  - [The Tel Hashomer camptodactyly syndrome].
AB  - Tel Hashomer camptodactyly syndrome in 2 siblings was described for the first
      time in Russian literature. Together with camptodactyly flexion folds between
      phalanges were absent in patients and characteristic face alterations were
      presented such as asymmetry, hypertelorism, antimongolian ophthalmic eyes cut,
      high ridge of the nose. There were also observed diffuse skeletal musculature
      hypoplasia together with humeroradial muscle aplasia as well as two-sides
      talipes. Inheritance type of syndrome in this family was estimated as autosomal
      recessive.

PMID- 8533520
TI  - [The treatment of migraine].

PMID- 8533521
TI  - [The efficacy of alprazolam in the therapy of panic disorders].
AB  - 22 patients with panic disorder (diagnosis according to ICD-10) were treated with
      alprazolam (monotherapy) in a dose of 1-2,5 mg/daily during 6 weeks.
      Disappearance of panic attacks was observed in 59% of cases while in 27% of
      patients they arose more rarely. The drug's antipanic action was revealed during
      second week of treatment. The side-effects were typical for benzodiazepine
      preparations. No one patient refused of drug administration in connection with
      side-effects development. Prognostically unfavourable signs were found: the high
      frequency of panic attacks, the presence of atypical marked permanent symptoms in
      attack structure, as well as the steady vegetative disturbances presence.

PMID- 8533522
TI  - [The tension headache].

PMID- 8533523
TI  - [The use of the contingent negative wave in neurology and psychiatry].

PMID- 8533524
TI  - Molecular diagnostics in the clinical laboratory: a plea for prudence!

PMID- 8533525
TI  - Epidemiology of interstitial lung disease (ILD) in flanders: registration by
      pneumologists in 1992-1994. Working group on ILD, VRGT. Vereniging voor
      Respiratoire Gezondheidszorg en Tuberculosebestrijding.
AB  - Worldwide almost no epidemiologic data are available on the prevalence or
      incidence of interstitial lung diseases (ILD) in the general population.
      Therefore, a registration programme of ILD-prevalence was organised by the VRGT
      (Vereniging voor Respiratoire Gezondheidszorg en Tuberculosebestrijding), among
      about 100 Flemish pneumologists since 1990. Most categories of the classification
      by Crystal et al. (1) were included and the diagnostic criteria (histology,
      laboratory tests, clinic, radiology) were registered. The present paper presents
      the results of 1992-1994: twenty pneumologists had forwarded the summary files of
      237 patients to the central office in 1992 (n = 68), 1993 (n = 90) and 1994 (n =
      79). The diagnoses that were most frequently made were: sarcoidosis in 27%,
      idiopathic pulmonary fibrosis in 20%, hypersensitivity pneumonitis in 14% (of
      which 68% by birds) and collagen-vascular disease in 10% (of which 54% in
      rheumatoid arthritis). Less frequent causes were eosinophilic pneumonia (4%),
      inhalation of inorganic material (4%, anthracosilicosis being excluded),
      histiocytosis X (3%), drugs (3%), angiitis and granulomatosis (2%), pulmonary
      hemosiderosis (1%), lymphocytic infiltrative lung disease (1%) and
      lymphangioleiomyomatosis (1%). The order of relative frequencies of the different
      categories of diseases was the same in the 3 registration years. In 9% of the
      patients the diagnosis was confined to "undefined fibrosis". The diagnosis was
      confirmed by histology in 63% of the cases. The overall male-female ratio was
      nearly one, with, however, a male preponderance in hypersensitivity pneumonitis
      (22/12), UIP(8/3) and "undefined fibrosis" (14/7).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8533526
TI  - Infectious gastroenteritis: are they all the same?
AB  - Campylobacter jejuni and Salmonella spp are the most frequently cultured micro
      organisms in infectious gastroenteritis among patients hospitalized at the
      departments of gastroenterology and geriatrics. As a whole, the hospitalized
      patient population with Campylobacter gastroenteritis is a younger one, compared
      to the Salmonella-infected group. Both pathogens can be associated with a
      biochemical pancreatitis, which is usually without clinical importance. However,
      serious complications can occur, with a predominance of visceritis for C. jejuni,
      and renal function impairment for Salmonella spp. Finally, an asymptomatic
      carrier state is well known in the Salmonella infection spectrum, whereas C.
      jejuni might cause a recurrent disease in some patients.

PMID- 8533527
TI  - In vitro activity of piperacillin/tazobactam against recent clinical isolates
      from hospitalized patients in ten Belgian hospitals.
AB  - The in vitro activity of the combination piperacillin/tazobactam has been
      compared to that of piperacillin, ticarcillin/clavulanate, cefotaxine,
      ceftazidime, imipenem and ciprofloxacin against 678 Enterobacteriaceae, 173
      nonfermenters, 185 staphylococci, 96 E. faecalis, 217 S. pneumoniae, 202 H.
      influenzae and 178 M. catarrhalis isolated from hospitalized patients.
      Piperacillin/tazobactam was similar in activity to third generation
      cephalosporins, imipenem and ciprofloxacin, and more active than piperacillin
      alone and ticarcillin/clavulanate.

PMID- 8533528
TI  - Progressive mediastinal widening after therapy for Hodgkin's disease.
AB  - A residual mass after treatment of Hodgkin's disease points to the diagnosis of
      fibrotic residue or of persistent disease. Radiological and radionuclide imaging,
      although helpful, cannot differentiate between both conditions with absolute
      certainty. Thus, residual masses are followed up: stable or regressive masses
      strengthen the hypothesis of fibrotic residue, while enlarging masses evoke
      relapsing disease. We report on a patient with an enlarging residual mass after
      completion of therapy, which proved to be a benign thymic hyperplasia after
      histological analysis. Previously reported similar observations are reviewed.

PMID- 8533529
TI  - Cyclospora sp.: a coccidian that causes diarrhoea in travellers.
AB  - Cyclospora sp. is a coccidian (protozoan) that has been incriminated in cases of
      diarrhoea in particular among travellers. We report two cases of intestinal
      Cyclospora infection in immunocompetent Belgians, who travelled to Indonesia.
      Although the diarrhoea persisted for several days recovery seemed to occur
      spontaneously.

PMID- 8533530
TI  - [Wegener's granulomatosis: clinical, radiological and diagnostic characteristics.
      Apropos of a case].
AB  - The authors report an observation of Wegener's granulomatosis with pulmonary,
      bronchial, renal, cutaneous and sinusal involvement. Five years ago, the patient
      was referred to us because of bilateral diffuse pulmonary infiltrates of unknown
      origin. A corticotherapy was introduced at that time and a complete clearance of
      the pulmonary infiltrates was noted. Nineteen months after the treatment's
      withdrawal, the disease recurs with the reappearance of pulmonary infiltrates.
      Beyond these unusual clinical aspects, histological examination of the bronchial
      biopsies were of diagnostic value.

PMID- 8533531
TI  - Digital necrosis associated with chronic myeloid leukemia: a rare paraneoplastic
      phenomenon.
AB  - We describe the case of a 72-year-old man who developed unilateral digital
      necrosis, four years after diagnosis of chronic myeloid leukemia (CML). The
      etiology of this paraneoplastic phenomenon appears multiple. The digital necrosis
      responded well to an aggressive varied treatment. The unusual association of CML
      with digital necrosis and the etiology of this rare paraneoplastic complication
      are discussed.

PMID- 8533532
TI  - [Major prolongation of the QT interval observed in the course of massive
      pulmonary embolism].
AB  - The authors report the case of a 68-year-old woman who suffered from an acute
      massive pulmonary embolism. The common electrocardiographic findings were not
      observed, but rather an extreme QT prolongation. The patient has been
      successfully treated by thrombolysis. After a few days, the electrocardiogram
      normalized. These electrocardiographic changes have not yet been described in the
      medical literature.

PMID- 8533533
TI  - Tuberculous pleural effusion following coronary artery bypass graft.
AB  - We present two patients with moderate left ventricular dysfunction, who developed
      a pleural effusion after coronary artery bypass grafting (CABG). The effusion was
      proven to be an exsudate of tuberculous origin. This illustrates that not all
      pleural exsudates developing after CABG are due to a post-pericardiotomy
      syndrome. Therefore microbiological examination of pleural fluid and if necessary
      pleural biopsy should be performed in all patients with an unresolving pleural
      effusion following CABG.

PMID- 8533534
TI  - Combined Conn's and Cushing's syndrome: an unusual presentation of adrenal
      adenoma.
AB  - In most aldosterone-producing adenomas (APA) dedifferentiation occurs with
      formation of transitional cells, bearing characteristics of both glomerulosa and
      fasciculata cells. These cells are able to produce cortisol, and their
      aldosterone production follows the circadian rhythm of ACTH. Usually, no clinical
      signs of cortisol excess develop, since the cortisol production remains under
      ACTH feedback control. Only a few cases have been described with autonomous
      cortisol secretion, not suppressible by low dose dexamethasone. We present a
      patient with an APA, synthesizing enough cortisol to cause the typical clinical
      expression of Cushing's syndrome. Possible etiopathological mechanisms are
      discussed.

PMID- 8533535
TI  - Catheter-related intracardiac thrombosis: a rare complication of Candida glabrata
      sepsis.
AB  - A 58-year-old patient suffered from persistent Candida glabrata fungaemia.
      Transoesophageal echocardiography detected a central venous catheter-related
      intracardiac thrombosis. Cardiotomy permitted the removal of the catheter and its
      adherent clot. Candida glabrata was cultured from the thrombus.

PMID- 8533536
TI  - Benzylisoquinolinium Muscle Relaxants: Innovations asn Issues. Proceedings from a
      meeting. Geneva, Switzerland, January 14-16, 1994.

PMID- 8533537
TI  - Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle
      relaxants.
AB  - The benzylisoquinolinium class of drugs comprises atracurium, 51W89, doxacurium,
      and mivacurium. Atracurium can be used as a pharmacokinetic benchmark; it has at
      least two distinct metabolic pathways, of which Hofmann elimination and ester
      hydrolysis are the most significant. The relative importance of each of these two
      routes is still a matter of speculation, and this, coupled with the fact that
      atracurium is a mixture of 10 isomers, has led to the development of many
      innovative pharmacokinetic modelling concepts. 51W89 is a cis-cis-isomer of
      atracurium and probably has a pharmacokinetic profile very similar to that of
      atracurium. Doxacurium, a long-acting benzylisoquinolinium, has a small apparent
      volume of distribution and an elimination half-time similar to that of
      pancuronium, and is excreted by the kidneys. Mivacurium is a short-acting
      benzylisoquinolinium that is rapidly hydrolysed by plasma cholinesterases. Two
      isomers of mivacurium are very similar, whereas the third isomer differs greatly
      in both pharmacological activity and elimination half-time, so that analysis
      requires complex pharmacokinetic methods.

PMID- 8533539
TI  - Fifty years of muscle relaxants.
AB  - The introduction of curare improved surgical relaxation and encouraged
      anaesthetists to enlarge their vision. They became interested in the
      pharmacologic properties of their drugs and the physiologic changes associated
      with paralysis, and this led naturally to their involvement in intensive care and
      respiratory physiology. Since 1942, more than 50 muscle relaxants have been
      introduced: the current emphasis is on the short- to intermediate-duration agents
      that allow rapid recovery and avoid the problems associated with residual
      curarization, but we still await a nondepolarizing replacement for suxamethonium.

PMID- 8533538
TI  - The clinical and basic pharmacology of mivacurium: a short-acting nondepolarizing
      benzylisoquinolinium diester neuromuscular blocking drug.
AB  - Mivacurium is a benzylisoquinolinium diester. The drug is a nondepolarizing
      relaxant which is hydrolysed by plasma cholinesterase at 70-88% of the rate of
      suxamethonium. Enzymatic hydrolysis gives the drug its short duration of action.
      The length of paralysis is about 2-2.5 times that of suxamethonium and one-half
      to one-third that of the intermediate-acting nondepolarizers. The development of
      mivacurium represents a collaboration between industrial pharmacologists and
      chemists at Burroughs Wellcome Co. (USA) and investigators at the Massachusetts
      General Hospital, Boston, MA, USA.

PMID- 8533540
TI  - Mivacurium chloride--a comparative profile.
AB  - Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline
      type. Its short duration of action is due to rapid breakdown by plasma
      cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch
      response (ED95) is between 60 and 80 micrograms/kg. Thus, mivacurium is 0.8 times
      and four times as potent as vecuronium and atracurium, respectively. With 2-3 x
      ED95, tracheal intubation can be accomplished within 2.5 min of intravenous
      injection. The ensuing DUR25% (time from injection to 25% recovery of control
      twitch tension) is twice as long as with suxamethonium and about half as long as
      with equipotent doses of atracurium or vecuronium. For muscle relaxation during
      long surgical procedures, mivacurium has been used as a continuous infusion. The
      average 6-min recovery index after infusion of mivacurium is particularly
      favourable for flexible control of muscle paralysis, whereas the recovery indices
      after infusion of atracurium or vecuronium are 15-30 min. In conclusion,
      mivacurium will close the pharmacodynamic gap between suxamethonium and the
      nondepolarizing muscle relaxants of intermediate duration of action. It will
      probably also be a suitable alternative to suxamethonium in elective cases.

PMID- 8533541
TI  - Intubating conditions and neuromuscular effects of mivacurium during propofol
      alfentanil anaesthesia.
AB  - In three groups of 20 patients, anaesthetized with propofol and alfentanil,
      tracheal intubation conditions and the onset of neuromuscular blockade after
      administration of three different doses of mivacurium chloride (0.11, 0.15, and
      0.19 mg/kg = 1.5 x ED95, 2 x ED95, and 2.5 x ED95) were assessed. Intubation
      conditions were found to be clinically acceptable (good or excellent) in 83% of
      patients. Eighty-two per cent of patients were successfully intubated on the
      first attempt after 60-90 s. No difference in intubation scores or number of
      intubation attempts among the three dosage groups were found. We conclude that
      mivacurium chloride allows smooth intubation in most patients within 60-90 s,
      even with the lowest dose (0.11 mg/kg), after a propofol-alfentanil induction of
      anaesthesia. However, because there were a few patients in whom intubating
      conditions were inadequate at 60-90 s, we are reluctant to advocate the
      preference of mivacurium chloride over suxamethonium for rapid sequence induction
      in emergency situations.

PMID- 8533542
TI  - Mivacurium in short to intermediate surgical procedures.
AB  - Mivacurium, a new benzylisoquinoline muscle relaxant, appears to be close to the
      ideal for short to intermediate surgical procedures. Ideal properties of such an
      agent are discussed, in addition to indications for muscle relaxation in such
      procedures. Two studies are presented, showing the onset and offset times of
      mivacurium and its cardiovascular stability in both young and elderly patients.
      It is concluded that it is a well-tolerated and appropriate agent for use in
      short to intermediate surgical procedures in those patients with normal plasma
      cholinesterase function, despite a slight prolongation of action in the elderly.

PMID- 8533543
TI  - Comparison of the neuromuscular effects of mivacurium and suxamethonium in
      infants and children.
AB  - We compared both the time course of neuromuscular blockade and the cardiovascular
      side-effects of suxamethonium and mivacurium during halothane and nitrous oxide
      anaesthesia in infants 2-12 months and children 1-12 years of age. Equipotent
      doses of mivacurium and suxamethonium were studied; 2.2 x ED95 was used in four
      groups of infants and children, while 3.4 x ED95 was used in two groups of
      children. Onset of neuromuscular block in infants was not significantly faster
      with suxamethonium than with mivacurium (P = 0.2). In all infants given
      suxamethonium, intubating conditions were excellent, while, in 6/10 infants given
      mivacurium, intubating conditions were excellent. Onset of complete neuromuscular
      block in children was significantly faster with suxamethonium, 0.9 min compared
      with mivacurium, 1.4 min (P < or = 0.05). Increasing the dose of suxamethonium or
      mivacurium in children to 3.4 x ED95 did not change the onset of neuromuscular
      block. Recovery of neuromuscular transmission to 25% of initial twitch height
      (T25) in infants and children was significantly faster after suxamethonium than
      after mivacurium, at 2.5 and 6 min, respectively (P < or = 0.05). In children
      given 3.4 x ED95 of suxamethonium or mivacurium, recovery from neuromuscular
      block was almost identical with the dose of 2.2 x ED95, with spontaneous recovery
      to T25 prolonged by only 0.5 min. No infant or child had hypotension after the
      mivacurium bolus dose.

PMID- 8533544
TI  - Mivacurium chloride in infants and children.
AB  - Mivacurium has been little studied in infants and children without a volatile
      anaesthetic agent. We analysed onset time and maximal neuromuscular response
      after mivacurium 0.1 mg/kg, and the infusion requirement of mivacurium to
      maintain a 50, 90, or 95% neuromuscular block in 76 infants and children under
      N2O-O2-alfentanil anaesthesia. Furthermore, we assessed the time course of
      potentiation of 1 MAC end-tidal halothane or isoflurane on the infusion
      requirement of mivacurium. Neuromuscular response was recorded by adductor
      pollicis electromyogram. The onset time of mivacurium was shorter in infants than
      in children (2.1 +/- 0.6 and 3.2 +/- 0.9 min (mean +/- SD); P = 0.0001). The dose
      potency of mivacurium did not depend on the age of a paediatric patient. The
      estimated ED95 of mivacurium was 136 +/- 46 micrograms/kg. The mivacurium
      requirement to maintain a 50, 90, or 95% neuromuscular block averaged 340, 730,
      and 900 micrograms/kg/h, respectively. Halothane and isoflurane decreased this
      hourly requirement by 35 and 70%, respectively. The decrease in the mivacurium
      infusion requirment was fastest in the youngest children. In conclusion,
      mivacurium is easy to administer as bolus doses or continuous infusion in
      paediatric patients because its potency is similar in all patients from 1 month
      to 15 years of age. Halothane and isoflurane produce their maximal potentiation
      of neuromuscular block only after 30-60 min of administration. This potentiation
      is similar in magnitude in all patients, but takes place fastest in the youngest
      children.

PMID- 8533545
TI  - The influence of ageing on the pharmacodynamics of mivacurium chloride.

PMID- 8533546
TI  - Mivacurium in special patient groups.
AB  - In special patient groups, drug response may be different from that in the
      healthy adult patient. Mivacurium dose requirements vary with age, and children
      require larger doses to obtain any given degree of block, but the elderly often
      require smaller doses. However, the dose requirements of the neonate do not
      necessarily differ greatly from those of the adult. There is a relationship
      between the duration of action of a bolus dose as well as infusion requirements
      to maintain block and the plasma cholinesterase activity. Patients with renal
      disease may have a decreased cholinesterase activity and may require smaller
      doses of mivacurium. Patients with severe liver disease may have a marked
      decrease in cholinesterase activity, and in these patients a substantially
      smaller dose of the drug may be needed to obtain and maintain any given degree of
      block. If the variation in dose requirements is kept in mind and the degree of
      block appropriately monitored, mivacurium may be used with safety in special
      patient groups, such as children, the elderly, or those with renal or hepatic
      impairment.

PMID- 8533547
TI  - Mivacurium chloride administration by infusion.
AB  - As a consequence of its rapid hydrolysis by plasma cholinesterase, mivacurium has
      a short duration of action, and recovery from neuromuscular blockade is rapid (5
      95% twitch recovery = 13-15 min). Mivacurium is easy to titrate to individual
      patient requirements; the average infusion rate to maintain neuromuscular
      blockade at 89-99% twitch suppression during N2O/opioid anaesthesia is 6-7
      micrograms/kg per min in adults and approximately 14 micrograms/kg per min in
      children. There is no evidence of a cumulative effect of mivacurium; recovery is
      unaffected by dose administered or duration of infusion. These characteristics
      make mivacurium a very suitable agent for use by infusion.

PMID- 8533548
TI  - The role of muscle relaxants in total intravenous anaesthesia.
AB  - For total intravenous anaesthesia (TIVA), all drugs that are required as part of
      the anaesthetic method are administered intravenously. This is usually taken to
      imply the use of intravenous infusions. It is normal practice to administer
      muscle relaxants intravenously, although other routes have been used. A muscle
      relaxant is required firstly to secure paralysis and secondly to maintain
      paralysis. The rate of onset of all the nondepolarizing neuromuscular blocking
      agents which are routinely available at present is similar; it takes about 3-6
      min for a normal clinical dose to reach maximum effect. Maintenance of an
      adequate level of block is necessary, and it is usually helpful to the surgeon
      for the level of block to be relatively constant. The choice of drug is
      important. It should cause negligible side-effects. For administration by
      infusion, an agent with an intermediate (e.g., atracurium) or short (e.g.,
      mivacurium) duration of action is essential to ensure a rapid recovery of effect
      on termination of the infusion. The routine use of neuromuscular monitoring is
      recommended when a continuous infusion of a relaxant is used.

PMID- 8533549
TI  - Spontaneous recovery or evoked reversal of neuromuscular block.
AB  - Recovery from the effects of muscle relaxants can occur either spontaneously by
      their metabolism in the body or by elimination via the normal excretion pathways,
      or by the administration of pharmacologic antagonists. The decision as to whether
      spontaneous recovery should be allowed to take place or pharmacologic reversal
      should be induced depends upon several factors, principal among them being the
      duration of action of the muscle relaxant used, its dose, and the time that is
      available. The recovery times of most relaxants, including atracurium and
      vecuronium, are such as to require antagonism if adequate recovery is to be
      attained quickly. An agent such as mivacurium may, however, allow complete
      spontaneous recovery to take place without the use of antagonists.

PMID- 8533550
TI  - Effect of neostigmine at different levels of mivacurium-induced neuromuscular
      blockade.
AB  - The effectiveness of neostigmine 40 micrograms/kg for antagonism of two different
      levels of neuromuscular blockade, induced by a bolus dose of mivacurium 0.15
      mg/kg, was studied in 45 patients. The patients were anaesthetized with
      thiopentone, fentanyl, nitrous oxide in oxygen, and enflurane. Neostigmine was
      administered at either 10% recovery of the twitch height (TH10) at the adductor
      pollicis muscle (n = 14) or upon reappearance of the first response at the
      orbicularis oculi muscle (OO1) after train-of-four (TOF) stimulation (n = 16),
      the latter representing a deeper degree of neuromuscular blockade. Fifteen of the
      45 patients did not receive neostigmine (control group). Neostigmine
      administration at OO1 rather than at TH10 at the adductor pollicis muscle caused
      reversal of neuromuscular blockade to occur 8 min earlier and shortened the time
      to reach 25% recovery of the twitch height (TH25) at the adductor pollicis muscle
      by about 5 min, compared with the control group. However, the time needed to
      reach a T4/T1 ratio > or = 0.8 was similar in both the early and late neostigmine
      administration groups, being 9 min faster than in the control group. It can be
      concluded that there is no advantage in administering neostigmine at profound
      neuromuscular blockade to achieve clinically adequate recovery (T4/T1 ratio > or
      = 0.8). However, the time between injection of mivacurium and TH25 may be
      shortened by using neostigmine at profound neuromuscular blockade, a procedure
      which may be useful in case of unpredictably difficult intubation, since
      diaphragmatic movements usually reappear at TH25.

PMID- 8533551
TI  - Muscle relaxants and histamine release.
AB  - Many anaesthetic drugs and adjuvants can cause the release of histamine by
      chemical (anaphylactoid) or immunologic (anaphylactic) mechanisms. While both
      types of reactions can be clinically indistinguishable, they are mechanistically
      different. In anaphylactoid reactions, only preformed mediators are released, of
      which histamine may be the most clinically important. In true immunologic
      reactions, mast cell degranulation occurs, and many vasoactive substances
      (including histamine) are released. Clinical signs and symptoms of both classes
      of reactions include hypotension (most common), tachycardia, bronchospasm, or
      cutaneous manifestations. Anaphylactoid reactions may occur commonly under
      anaesthesia in response to many drugs, including induction agents, some opiates,
      plasma expanders, and curariform relaxants. Anaphylactic reactions are far less
      common than anaphylactoid reactions, but they nevertheless represent more than
      half of the life-threatening reactions that occur in anaesthetic practice. Muscle
      relaxants are the most frequently implicated class of drugs; suxamethonium is the
      most common agent implicated in anaphylactic reactions during anaesthesia, but
      even drugs without apparent chemical histamine release (i.e., vecuronium) are
      frequently implicated in anaphylactic reactions.

PMID- 8533552
TI  - The use of neuromuscular blocking drugs in intensive care practice.
AB  - Critically ill patients represent a very different population from that of the
      operating theatre, but much of our knowledge of many of the neuromuscular
      blocking drugs is derived from intraoperative use. The diversity of clinical
      practice and case-mix differences in intensive care are probably responsible for
      the absence of a formal consensus about the use of neuromuscular blocking drugs
      in the intensive care unit (ICU). Various surveys suggest that these drugs are
      used comparatively infrequently, but we do not know whether current usage is
      either safe or appropriate. In addition to the adverse effects which inevitably
      accompany prolonged paralysis and immobility, the steroidal relaxants,
      pancuronium and vecuronium, have also been associated with myopathy. This seems
      to be aggravated by concurrent use of pharmacologic doses of corticosteroids or
      the aminoglycoside antibiotics. Neither the mechanism nor the validity of the
      association with steroidal relaxants is known at present. Muscle dysfunction is a
      common feature of critical illness, and it is possible that neuromuscular
      blocking drugs interfere with muscle repair and regrowth. Patients with multiple
      organ failure present a particular challenge both because of the extent of tissue
      injury and because drug clearance via the liver or kidneys is generally impaired.

PMID- 8533553
TI  - Isomerism and anaesthetic drugs.
AB  - Isomers are two or more different substances with the same molecular formula
      (i.e., the same number of different types of atoms). There are two main types of
      isomerism: 1) structural isomerism, and 2) steroisomerism. Structural isomers
      (e.g., enflurane and isoflurane) have different molecular structures, and usually
      behave like different drugs. Occasionally, structural isomers are
      interconvertible (i.e., they are tautomers or dynamic isomers); this occurs with
      the barbiturates and midazolam. Steroisomers have identical structures, but a
      different configuration or spatial arrangement. Stereiosomerism in drugs is often
      due to chirality or "handedness"; i.e., the presence of right-handed (R)- and
      left-handed (S)- forms of drugs which are nonsuperimposable mirror images
      ("enantiomers"). Approximately 60% of anaesthetic agents are chiral drugs; some
      of these are administered as single enantiomers. However, many synthetic chiral
      drugs are equal mixtures of (R)- and (S)-isomers, and there are often important
      differences in their activity and pharmacokinetics. Halothane, enflurane, and
      isoflurane are chiral drugs with different anaesthetic potencies. Similar
      differences occur with intravenous anaesthetics; thus, (S) (+)-ketamine causes
      fewer psychotic emergence reactions, less agitated behaviour, and better
      intraoperative amnesia and analgesia than its enantiomer. Some local anaesthetics
      are administered as chiral mixtures; the (S)-isomers have a longer action because
      of enhanced vasoconstriction. (S)-prilocaine is more slowly metabolized than its
      enantiomer, while (S)-bupivacaine may produce less cardiotoxicity than (R)
      bupivacaine. These differences suggest that some anaesthetic drugs (particularly
      ketamine and chiral local anaesthetics) should be administered as single
      enantiomers. In recent years, their synthesis has been greatly simplified, and
      almost all new drugs may soon be introduced in this form.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8533554
TI  - The future of the benzylisoquinolinium relaxants.
AB  - The benzylisoquinolinium relaxants currently include the intermediate-acting
      agent, atracurium, and the short-acting agent, mivacurium. This class of
      relaxants has always retained the distinct advantages of rapid degradation,
      enzymatic metabolism, or both in the plasma, resulting in short half-lives and
      fast, complete recovery, unrelated to dose or duration of administration. Any
      improvements in this class of relaxants must focus on retaining this property at
      the same time as decreasing or eliminating histamine release, which has always
      been the major disadvantage of the benzylisoquinoliniums. The introduction of
      51W89, an isomer of atracurium, may represent an advance in the development of
      this class of relaxants.

PMID- 8533555
TI  - Pharmacokinetics of 51W89: preliminary data.
AB  - The pharmacokinetics of the 1R cis-1'R cis-isomer of atracurium (51W89) and its
      metabolite, laudanosine, were studied in 11 healthy patients with normal renal
      function and in 12 patients with chronic renal failure undergoing regular
      dialysis. A bolus dose of 51W89 (0.1 mg/kg) was given, and the plasma
      concentration was measured at regular intervals for 480 min. The elimination half
      life of 51W89 was significantly longer in renal failure patients than in healthy
      controls (38.9 min vs 30.6 min; P < 0.05). The plasma laudanosine levels were
      lower than those reported after an equipotent dose of atracurium besylate. 51W89
      may have a prolonged effect in renal failure patients.

PMID- 8533556
TI  - Administration of 51W89 by infusion--a comparison with atracurium--preliminary
      communication.

PMID- 8533557
TI  - The female corpus spongiosum revisited.
AB  - BACKGROUND: The extension of the female corpus spongiosum is subject to
      controversy. The anterior continuation of the vestibular bulbs, or pars
      intermedia, is not commonly recognized as part of the corpus spongiosum. Some
      authors deny this part of the corpus spongiosum exists in females. MATERIAL AND
      METHODS: To investigate this controversy, anatomic and histologic studies were
      performed of the female corpus spongiosum. The specimens were taken from female
      to-male transsexual surgical patients and from fresh female cadavers. They were
      compared to surgically amputated penises to establish the similarity in male and
      female anatomy. RESULTS--CONCLUSIONS. The female corpus spongiosum is proven to
      extend anteriorly from the bilateral vestibular bulbs to terminate as the
      enlarged glans clitoridis. This latter structure also consists of spongious
      tissue. The spongiosum is hypertrophied in hormonally treated female-to-male
      transsexuals. The cleft vulvar anatomy is homologue to its non-cleft male
      counterpart.

PMID- 8533558
TI  - Death rates from ischemic heart disease in women with a history of hypertension
      in pregnancy.
AB  - BACKGROUND: Evidence about the influence of hypertension in pregnancy on later
      health and in particular the risk of cardiovascular disorders is conflicting,
      although a link has been suggested. In a population-based study with a long
      follow-up time the potential association between hypertension in pregnancy,
      preeclampsia and eclampsia with increased death rates from ischemic heart disease
      (IHD) was investigated. METHODS: All 7543 case records at the main maternity
      hospital in Iceland during 1931-1947 were reviewed to identify women with
      hypertension in pregnancy, subdivided by parity and severity of disease into
      those with eclampsia, preeclampsia and hypertension alone. Information on those
      who had died was obtained from death certificates, supplemented by autopsy
      reports and hospital records. Death rates from IHD were compared to population
      data from public health and census reports during corresponding periods and
      between study groups. RESULTS: Of 374 hypertensive women 177 had died. The death
      rate was slightly higher among women with any hypertension in pregnancy than in
      the reference population (RR = 1.20; 95% CI 1.01-1.42). About half of the
      increase was attributed to excess mortality from IHD with a relative risk of
      dying of 1.47 (95% CI 1.05-2.02). The relative risk of dying from IHD was
      significantly higher among eclamptic women (RR = 2.61; 95% CI 1.11-6.12) and
      those with preeclampsia (RR = 1.90; 95% CI 1.02-3.52) than those with
      hypertension alone. Parous women at the index pregnancy had a twofold higher risk
      of dying from IHD than primigravid women (RR = 2.05; 95% CI 1.19-3.55; p = 0.01).
      CONCLUSION: There is an indication of increased death rates among women with a
      history of hypertension in pregnancy, where ischemic heart disease may be more
      common than in the general population.

PMID- 8533559
TI  - Alloimmunization during pregnancy treated with high dose intravenous
      immunoglobulin. Effects on fetal hemoglobin concentration and anti-D
      concentrations in the mother and fetus.
AB  - BACKGROUND: High dose intravenous immunoglobulin has been reported to be
      advantageous in the treatment of alloimmunization during pregnancy. The mode of
      action is unknown. METHOD: High dose intravenous immunoglobulin was used as the
      sole prenatal treatment in six severely rhesus(D) sensitized pregnant women.
      Maternal and fetal anti-D concentrations as well as fetal hemoglobin
      concentrations were studied. Seven pregnancies in rhesus(D) sensitized women
      served as controls. They received no treatment because they had milder forms of
      erythroblastosis fetalis or, in one case, a rhesus(D) negative fetus. RESULT: No
      obvious inhibitory effect of the treatment on maternal anti-D production and
      transplacental anti-D passage to the fetus was found. The fetal hemoglobin
      concentrations remained stable at about 80 g/L (hematocrit 27%) in five of six
      treated patients while there was a significant decrease in the control group.
      CONCLUSION: High dose intravenous immunoglobulin treatment seems to act mainly on
      fetal red cell destruction rate, possibly by blocking Fc receptor mediated
      macrophage phagocytosis. We claim that the treatment can successfully be used to
      prevent further deterioration of fetal anemia in rhesus(D) immunizations if
      started before severe fetal anemia (hemoglobin concentration < 70 g/L, hematocrit
      < 23%) and imminent hydrops fetalis arises.

PMID- 8533560
TI  - Chronological changes in subjective symptoms during pregnancy in nulliparous and
      multiparous women.
AB  - BACKGROUND: To investigate chronological changes of subjective symptoms during a
      normal pregnancy in nulliparous and multiparous women. METHODS: Prospective data
      were collected using a 20-item questionnaire (general fatigue, headache,
      palpitation, nausea/vomiting, fever, insomnia, edema, abnormal abdominal size,
      urinary frequency, lumbago, fetal descent, genital bleeding, watery discharge,
      high frequency of uterine contraction, increase in frequency of uterine
      contraction, strong intensity of uterine contraction, increase in intensity of
      uterine contraction, no change of uterine contraction at rest, high frequency of
      fetal movements, strong intensity of fetal movements) at Tsushima Izuhara
      Hospital in Nagasaki Prefecture, Japan. Seven hundred and twenty-nine nulliparous
      and 588 multiparous normal pregnant women were questioned from 1988 to 1992. A
      simple (chi-square test) analysis of appearance percentages in each item for
      every term of pregnancy was made. RESULTS: Each symptom showed different
      chronological patterns. In the simple analysis, there were significant
      differences (p < 0.05) in 10 symptoms (headache, palpitation, fever, insomnia,
      lumbago, fetal descent, watery discharge, increase in frequency of uterine
      contraction, strong intensity of uterine contraction, strong intensity of fetal
      movements) between nulliparous and multiparous subjects. In the multiparous
      group, there was a higher severity in eight of the ten symptoms, except for fever
      and watery discharge. CONCLUSIONS: The multiparous group had more complaints than
      did the nulliparous subjects. These normal patterns are of practical clinical use
      concerning subjective symptoms of pregnancy.

PMID- 8533561
TI  - Hypertensive disorders of pregnancy and stillbirth in North Carolina, 1988 to
      1991.
AB  - BACKGROUND: The objectives of this study were (i) to assess the effect of
      hypertensive disorders of pregnancy on the risk of stillbirth, and (ii) to
      characterize the relationship between hypertension and stillbirth separately by
      gravidity, race, 'explained' versus 'unexplained' causes of stillbirth, and
      antepartum versus intrapartum stillbirths. METHODS: The study was based on a
      retrospective cohort of approximately 400,000 pregnancies identified through the
      birth and fetal death certificates in North Carolina, USA, between 1988 and 1991.
      Multivariable polytomous logistic regression was used to generate odds ratios
      comparing stillbirth risk in hypertensive compared to non-hypertensive mothers,
      adjusted for potential confounders. RESULTS: The risk of chronic hypertension was
      7.6 per 1000 pregnancies, while pregnancy-induced hypertension (PIH) and
      eclampsia were reported in 36.6 and 6.0 per 1000 pregnancies, respectively.
      Pregnancies among chronic hypertensives were more likely to result in losses
      after 28 weeks gestation (RR = 3.29, 95% CI: 2.43-4.43), while the risk ratio was
      2.16 (95% CI: 1.45-3.22) for losses prior to 28 weeks' gestation. Pregnancies to
      patients with PIH were at 1.42 (95% CI: 1.15-1.79) times greater risk of
      terminating in late stillbirth, while the risk ratio for eclampsia was 2.23 (95%
      CI: 1.51-3.30). The risk ratio for 'explained' antepartum stillbirth was higher
      than intrapartum stillbirth for all of the hypertensive diseases. CONCLUSIONS:
      Hypertensive disorders were found to have a strong adverse impact on stillbirth
      suggesting that early diagnosis of hypertension during pregnancy and adequate
      medical intervention may help reduce the risk of stillbirth.

PMID- 8533562
TI  - Sexually transmitted diseases in Swedish women with experience of casual sex with
      men of foreign nationalities within Sweden.
AB  - BACKGROUND: This study was performed in women who had attended the clinic for
      contraceptive advice to determine whether a history of casual sex with a foreign
      male, previously unknown to them (SFM) in their home country (Sweden),
      constituted an increased risk for acquiring sexually transmitted diseases (STD)
      as compared to women without such an experience (COMP). METHODS: Of 996 women
      enrolled, and who were subjected to a structured deep-interview performed by
      midwives, 595 (59.7%) stated that they had experienced casual sex within Sweden
      with for them a previously unknown Swedish male (SSM). RESULTS: A history of SFM
      was reported by 120 (12.0%) women. A history of chlamydial infection (26.0%) and
      gonorrhea (13.0%) were more common in the SFM women than in either the COMP
      (16.0% and 3.0%) or the SSM (19.0% and 4.0%) groups. Genital warts (8.0%) and
      bacterial vaginosis (23.0%) were found more often in the SFM group as compared to
      both the COMP (3.0% and 12.0%) and the SSM (4.0% and 13.0%) group. Women in the
      SFM group more often had a current genital chlamydial infection (13.0%) than
      those in the COMP group (8.0%). When adjustment was made for markers of sexual
      risk taking, only genital warts remained significantly (p = 0.05) associated with
      SFM as compared to both SSM and COMP. CONCLUSIONS: To conclude, the study shows
      that women with experience of SFM had, more often, a history of one or more STDs
      and were more often carriers of STD agents than those lacking experience of SFM
      and/or SSM. However, there was no such difference when comparing the SFM and SSM
      women when making adjustments for sexual risk behavior. Thus a sexual risky
      lifestyle is more important than the origin of the sex partner for acquiring STDs
      with possible exception of HIV/AIDS in the society studied.

PMID- 8533563
TI  - Conjunctiva is an estrogen-sensitive epithelium.
AB  - BACKGROUND: To investigate whether the conjunctival epithelium shows cyclical
      maturation changes during the ovarian cycle and to study the cytological
      appearance of the conjunctiva in postmenopausal and pregnant women. PATIENTS:
      Fifteen menstruating women with ovulatory cycles, ten postmenopausal women, and
      twelve pregnant women in the second or the third trimester of their pregnancy.
      INTERVENTIONS: Conjunctival and vaginal smears were taken on a near-daily basis.
      MAIN OUTCOME MEASURES: The percentage of the parabasal, the intermediate and the
      superficial cells (Maturation Index) in each specimen was determined. RESULTS: In
      the conjunctival smears of the menstruating women cyclical maturation changes
      were noted. These changes were parallel to those of the vaginal smears, but to a
      minor degree. No cyclical changes were found in either the postmenopausal women
      or in the pregnant women, showing an extreme shift to the left in the Maturation
      Index. CONCLUSION: Conjunctiva appears to be a relatively estrogen-sensitive
      epithelium.

PMID- 8533564
TI  - Treatment of premenstrual syndrome by spironolactone: a double-blind, placebo
      controlled study.
AB  - BACKGROUND: To reevaluate whether spironolactone, a steroid receptor antagonist,
      is effective in improving premenstrual syndrome (PMS) in a double-blind, placebo
      controlled cross over study. METHODS: Thirty-five women with PMS were given one
      tablet of 100 mg spironolactone or placebo daily from day 14 of the menstrual
      cycle until the first day of the following menstruation. Two pretreatment cycles
      were observed for diagnosis in each woman, followed by 6 treatment cycles with
      spironolactone and placebo applied in either the first or second 3 months. The
      assessment of symptoms and diagnosis of PMS were based on prospective daily self
      ratings made by the women using a validated visual analogue scale. RESULTS: The
      treatment with spironolactone was associated with an improvement in PMS symptoms
      compared to placebo as judged by significant decrease in negative mood symptom
      scores (p < 0.001) and somatic symptom scores (p < 0.001). Of the individual
      symptoms, spironolactone significantly improved irritability, depression, feeling
      of swelling, breast tenderness and food craving in comparison to placebo. A
      lasting effect of spironolactone was observed in women started with
      spironolactone after cross over to placebo. CONCLUSIONS: Spironolactone appears
      to be an effective therapy for the negative mood changes and somatic symptoms in
      PMS.

PMID- 8533565
TI  - Is misoprostol the drug of choice for induced cervical ripening in early
      pregnancy termination?
AB  - BACKGROUND: To study the effectiveness of three different cervical ripening
      agents in terms of dilatation ability and patient discomfort in connection with
      legal first trimester abortion. METHODS: Three randomized trials among unselected
      nulliparous women were performed 1: hygroscopic tent versus gemeprost, 2:
      misoprostol versus gemeprost and 3: misoprostol administered orally 17 versus 10
      hours before vacuum curettage was performed. MAIN OUTCOMES: Dilatation ability,
      frequent gastrointestinal side effects, severe pain (patients' perception).
      RESULTS: In Trial 1, there was a tendency of a greater dilatation ability using
      the hygroscopic tent, while the experience of pain was a greater problem with
      gemeprost. In Trials 2 and 3, there were no significant differences in the
      dilatation abilities or gastrointestinal patient discomfort. There was a tendency
      towards a higher demand for narcotic analgesics in patients treated with
      gemeprost compared with all other groups. CONCLUSIONS: Gemeprost and misoprostol
      showed almost identical ability to dilate and caused patient-experienced
      discomfort to the same degree. The use of misoprostol may be preferred as it has
      the advantage of being both less expensive and easier to administer.

PMID- 8533566
TI  - Ambivalence among women applying for abortion.
AB  - BACKGROUND: Our purpose was to characterize women expressing ambivalence when
      applying for abortion. MATERIAL AND METHODS: Data were collected, by self
      administered questionnaires, from 339 women. Thirty percent were in doubt about
      the decision when the abortion was due. Socio-economic factors more often
      influenced the choice among ambivalent women than among those not in any doubt.
      RESULTS: Ambivalent women more often felt exposed to social pressure and some
      felt that the abortion was not their own choice. Their decision-making was marked
      by doubt during the entire process. CONCLUSIONS: There is a need for professional
      support during this decision-making process. Many of the ambivalent women stated
      that their decision might not have been the same under different personal
      circumstances.

PMID- 8533568
TI  - Carbon dioxide laser miniconization for treatment of human papillomavirus
      infection associated with cervical intraepithelial neoplasia.
AB  - BACKGROUND: The effect of the carbon dioxide laser miniconization for treatment
      of cervical intraepithelial neoplasia with concomitant human papillomavirus
      infection was evaluated. MATERIAL AND METHODS: One hundred and eighteen women
      with cytologically proven cervical intraepithelial neoplasia stage 1 and/or 2
      were investigated with repeat vaginal smear, colposcopy and human papillomavirus
      DNA sampling. Seventy-five out of 118 women were subjected to laser
      miniconization or punch biopsy and cervical curettage. RESULTS: Out of 118
      patients 37 proved to have positive human papillomavirus DNA with one or more
      oncogenic types (31.4%). Of these, 32 women were miniconized and five subjected
      to punch biopsy or cervical curettage. On the first follow-up after
      miniconization all 32 patients were HPV negative. With follow-up up to five years
      no recurrences of HPV or dysplasia were seen. CONCLUSION: A miniconization
      procedure with carbon dioxide laser for treatment of cervical intraepithelial
      neoplasia proved useful also for simultaneous therapy of concomitant human
      papillomavirus infection of the uterine cervix.

PMID- 8533567
TI  - Reasons for pregnancy termination: negligence or failure of contraception?
AB  - BACKGROUND: The aim of the study was to analyze the reasons for the failure of
      contraception and the reasons for not using any contraception among women seeking
      a legal abortion on social grounds. The women were also asked about their
      knowledge of contraception methods, including postcoital contraception. METHODS:
      We interviewed 200 women applying for a legal abortion within the first trimester
      of pregnancy about contraception, the contraceptive methods used, and the
      possible reasons for failure of contraception. RESULTS: Of all the women
      interviewed, 93% claimed to have adequate knowledge of contraception. At the time
      of conception 11.5% used safe methods (OCs 8%, IUDs 3.5%), 63% used less safe
      methods, and 26% were without contraception. Only 25% of the pill users had no
      explanation for the failure. 76.7% of the condom users reported that the condom
      was broken, had slipped off or its use had been irregular. The concern about side
      effects was the most common reason for not using safe contraceptives (25%).
      CONCLUSIONS: The women claimed to have enough information about contraceptives,
      and postcoital contraception was also familiar, but the knowledge on how to use
      them in practice was inadequate. Irregular use and breaks in contraception were
      common. Despite the data based on Pearl indices, pills failed twice as often as
      IUDs. Counseling about the proper use of contraceptives is important, although
      the concern about the side effects appeared to be a big, unsolved problem.

PMID- 8533569
TI  - Magnetic resonance imaging (MRI) in endometrial carcinoma; preoperative
      estimation of depth of myometrial invasion.
AB  - BACKGROUND: The incidence of pelvic and aortic lymph node involvement in
      endometrial carcinoma depends on both tumor differentiation grade and myometrial
      invasion depth. It was evaluated whether magnetic resonance imaging (MRI)
      provides a preoperative technique to assess the depth of myometrial invasion.
      METHODS: The study includes 34 patients with an endometrial carcinoma. MRI (T5
      Gyroscan, Philips) was made a few days before operation. Myometrial invasion was
      divided in four categories. Cervical invasion was classified as absent,
      superficial or deep. For comparison an in vitro MRI of the uterus was made
      directly after the operation. Histo-pathological examination of the uterus was
      used as a golden standard of the depth of myometrial invasion. RESULTS: The
      estimation by MRI of the myometrial invasion depth was correct in 25 out of 31
      patients. In three patients estimation was not possible, because of bad image
      quality. In four patients the MRI underestimated the cervical invasion.
      CONCLUSIONS: Preoperative MRI in patients with an endometrial carcinoma can be
      used to estimate myometrial and cervical invasion. Therefore, in combination with
      the histological grading of the tumor, a preoperative MRI can be used to select
      patients at high risk of nodal involvement.

PMID- 8533570
TI  - Prenatal diagnosis of omphalocele associated with umbilical cord cyst.
AB  - BACKGROUND: To study the cytogenetics, ultrasound findings, biochemical
      screening, perinatal outcome, and associated abnormalities in cases of
      omphaloceles associated with umbilical cord cysts. METHODS: From 1988 to 1994,
      three cases of omphaloceles with umbilical cord cysts were identified at Mackay
      Memorial Hospital. We compared the clinical data of our three cases with six
      other cases in the published literature. RESULTS: Two cases of omphaloceles with
      umbilical cord cysts were affected with trisomy 18. One had bilateral choroid
      plexus cyst, intrauterine growth retardation, low levels of maternal serum alpha
      fetoprotein and free beta-human chorionic gonadotropin, and the other had cleft
      lip and palate, single umbilical artery and intrauterine growth retardation. An
      elevated level of maternal serum alpha-fetoprotein was found in the case with
      normal karyotype. Elevated levels of amniotic fluid alpha-fetoprotein were found
      in two cases. Rupture of the umbilical cord cyst and disruption of the umbilical
      cord occurred in one case at delivery. Based on the gross and microscopic
      examinations, the cord cysts we observed are likely to be pseudocysts.
      CONCLUSION: The umbilical cord cysts most commonly associated with omphaloceles
      are pseudocysts and allantoic cysts. Among our three cases and the six other
      cases published in the literature, four out of these nine cases were trisomy 18.
      Prenatal diagnosis of omphaloceles or umbilical cord cysts by ultrasound warrants
      cytogenetic analysis and detailed sonogram to rule out the possible combination
      of both abnormalities and trisomy 18. If an omphalocele is associated with a
      large umbilical cord cyst and a normal karyotype, cesarean section is recommended
      to prevent the dilemma of intrauterine vascular compromise of umbilical blood
      flow during labor.

PMID- 8533571
TI  - A case of pregnancy associated with cyclic neutropenia.

PMID- 8533572
TI  - Successful conservative management of placenta percreta with rectal involvement
      in a primigravida.

PMID- 8533573
TI  - Persistent postoperative urinary retention treated with transurethral
      intravesical electrostimulation.

PMID- 8533574
TI  - Carcinoma of the colon associated with high extragenital production of beta-hCG-
      a case report.

PMID- 8533575
TI  - An isolated case of Q-fever during pregnancy.

PMID- 8533577
TI  - Definition and treatment of severe preeclampsia.

PMID- 8533576
TI  - A rare case of extra lobar abdominal bronchopulmonary malformation.

PMID- 8533578
TI  - Consideration of Helicobacter pylori infection in childhood: immune response,
      endoscopic and morphological findings.
AB  - Seventy-five children (aged 9-14 years) infected with Helicobacter pylori were
      studied endoscopically and morphologically for the signs of infection and immune
      response by ELISA technique (total IgE and specific IgG against H. pylori); a
      control group of 36 children (not infected with H. pylori) were studied
      simultaneously. Helicobacter pylori positive children examined endoscopically
      revealed a number of mucous membrane changes including erythema, erosions,
      lymphoid nodular hyperplasia and ulcers. Gastritis was confirmed by histology in
      58 children; 6% were termed 'active', others were 'non-active'. When studying the
      concentrations of anti-H. pylori IgG in children from the control group they were
      considered to be seronegative but in children infected with H. pylori a
      considerable increase was noted. An evaluation of the interaction between anti-H.
      pylori IgG titers and age, endoscopic signs and histology was carried out.
      Suppositions were made about the presence of links between these characteristics.
      Children with H. pylori infection showed a considerable increase of total IgE
      titers in comparison with the control group. The role of IgG and IgE in the
      development of chronic gastroduodenal diseases associated with H. pylori is
      discussed.

PMID- 8533579
TI  - Patterns of 24 h intragastric acidity in duodenal ulcers in children: the
      importance of monitoring and inhibiting nocturnal acidity.
AB  - The objective of this study was to compare the gastric acidity patterns of
      patients with duodenal ulcers and normal children. Eight patients with duodenal
      ulcer had their intragastric pH monitored for two consecutive 24 h periods using
      intragastric glass electrodes. The first 24 h period elucidated pH patterns in
      the absence of treatment and the second period evaluated the acid suppressive
      effect of 15 mg/kg of cimetidine when given in three divided doses. Results
      showed that the ulcer patients were hyperacidic, particularly at midnight. This
      finding was in marked contrast to the results obtained in the study of normal
      controls. The mean pH of normal children was above 3 around midnight. This
      phenomenon is known as intragastric pH inversion. The mean pH 3 time (the
      cumulative duration of the time for which gastric pH is maintained at > or = pH
      3) was significantly shorter in patients with ulcers. However, pH 3 time of these
      patients significantly increased throughout the 24 h recording period during the
      daytime and at night after the introduction of cimetidine. This resulted in an
      induction of apparent nocturnal intragastric pH inversion for the ulcer patients.
      This study demonstrates the usefulness of 24 h continuous intragastric pH
      monitoring in children. The data showed that there was a pattern of gastric
      hyperacidity in pediatric ulcer patients which is clearly distinct from that of
      normal children, particularly in the patterns occurring at midnight. Cimetidine
      at 15 mg/kg per day in three divided doses was effective in suppressing secretion
      even at night.

PMID- 8533580
TI  - Immunogenicity and reactogenicity of the component acellular pertussis vaccine
      produced by a combination of column purified pertussis toxin and filamentous
      haemagglutinin.
AB  - This is the report on a prospective, single blind, comparative study of a
      component acellular pertussis vaccine produced by a combination of detoxified,
      column purified pertussis toxin (PT) and filamentous hemagglutinin (FHA) combined
      with diphtheria and tetanus toxoids (DTcaP) and the traditional acellular
      pertussis vaccine produced with essentially the same method as described by Sato
      with DT (DTaP) of the same manufacturer. A total of 616 infants and children
      received DTcaP and a total of 289 received DTaP. In all age groups for both
      vaccines values of serum antibodies to PT and FHA after two doses of the vaccines
      were comparable to those of convalescent sera. Incidences of systemic and local
      reactions were, in general, not greatly different between DTcaP and DTaP
      recipients. In Japan the use of traditional acellular vaccines replaced whole
      cell vaccines in 1981. Protective antigens of Bordetella pertussis have now been
      specified and thus component vaccines have become theoretically possible. This is
      the first component vaccine which has been developed in Japan. Several other
      component vaccines are now under investigation in the world.

PMID- 8533581
TI  - Detection of immunodeficiencies and persistent infections by urinary neopterin
      measurement.
AB  - We evaluated the clinical significance of measurement of urinary neopterin levels
      in primary immunodeficiencies and persistent infections exclusively at afebrile
      or asymptomatic periods. Despite the examinations at afebrile or asymptomatic
      periods, urinary neopterin levels were elevated in some patients with primary
      immunodeficiencies and in patients with persistent infections of human
      immunodeficiency virus (HIV) or Epstein-Barr virus (EBV). Therefore, urinary
      neopterin measurement at afebrile periods will be useful as one of the screening
      tests in the detection of such disorders among children with occasional episodes
      of infections.

PMID- 8533582
TI  - Application of a new perchloric acid treatment method to measure endotoxin by an
      endotoxin-specific chromogenic Limulus test in neonatal septicemia.
AB  - The endotoxin in blood was measured to establish both the cut-off value and to
      detect Gram-negative septicemia. We employed a new perchloric acid treatment
      method using an endotoxin-specific chromogenic Limulus test (Endospecy test). The
      cut-off value of endotoxin in blood was 11.2 pg/mL. All cases of septicemia (n =
      7) showed high values of endotoxin. Three cases were Group B streptococci, and
      two cases were Escherichia coli. The others were showed to be negative in blood
      cultures. The paired values of endotoxin titers during a 48 h interval were
      useful to evaluate the effectiveness of antibiotics.

PMID- 8533583
TI  - Lipoprotein (a) and apolipoprotein A-1 and B in schoolchildren whose grandparents
      had coronary and cerebrovascular events: a preliminary study of 12-13 year old
      Japanese children.
AB  - The aim of this study was to evaluate the relationship between the serum levels
      of lipoprotein (a) [Lp (a)] and apolipoproteins (apo A-1 and apo B) in
      schoolchildren with a history of coronary and cerebrovascular events in their
      grandparents. We measured serum concentrations of Lp (a) and apoliproteins
      immunochemically in 289 schoolchildren aged 12-13 years and questioned parents
      about coronary and cerebrovascular events in the children's grandparents. In boys
      and girls, mean +/- s.d. levels of apo A-1, apo B and Lp (a) were 134 +/- 20.3
      and 136 +/- 17.4 mg/dL, 61 +/- 16 and 66 +/- 15 mg/dL and 12.5 +/- 15.3 and 12.5
      +/- 15.1 mg/dL, respectively. There were no significant sex differences in the
      levels of apo A-1, apo B, and Lp (a). The Lp (a) levels (mean +/- s.d., 12.5 +/-
      15.2 mg/dL; median 7.5 mg/dL, n = 289) were not affected by other variables. The
      Lp (a) distribution was strongly positively skewed and 75% of schoolchildren had
      very low levels. In the total 289 schoolchildren, thirty-two grandparents who had
      had coronary vascular events (21 myocardial infarction, 11 angina pectoris) and
      twenty-three grandparents who had had cerebrovascular events were recorded. By
      the boxplot statistical analysis, no difference was found in Lp (a) levels in
      children whose grandparents had myocardial infarction compared with those whose
      grandparents had no such history, or compared with those whose grandparents had
      suffered cerebrovascular events.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533584
TI  - Multivariate autoregressive analysis of carotid artery blood flow waveform in an
      infant of a diabetic mother with cardiomyopathy.
AB  - We analyzed the carotid artery blood flow waveform (CABFW) of an infant of a non
      insulin dependent diabetic mother with hypertrophic cardiomyopathy (IDM
      cardiomyopathy) through multivariate autoregressive analysis and compared the
      developmental change of his CABFW with that of normal newborns. The total power
      was lower than normal newborns on the second and third day of life when his heart
      dysfunction was severe, and elevated on the fifth day of life when normal-heart
      function was recovered. The power of component 3 (C3), of which the damping
      frequency was 7-11 Hz, was slightly high on the second and third day of life and
      it decreased to the normal range on the fifth day of life by component analysis.
      In contrast, the power of C3 increased with decreasing resistance index of
      anterior cerebral artery (RI of ACA) which shows the cerebral vascular resistance
      of normal newborns. These results suggest that the carotid artery blood flow
      volume decreased by low cardiac output and the cerebral vascular resistance
      decreased to maintain the cerebral circulation, when the heart dysfunction was
      severe.

PMID- 8533585
TI  - Early detection of cutaneous microcirculatory change during hemorrhage using a
      laser Doppler flowmetry.
AB  - The purpose of the present study was to evaluate the usefulness of cutaneous
      microcirculatory monitoring during hemorrhage. We observed changes in cutaneous
      blood volume, velocity and flow of five adult rabbits during hemorrhage by using
      a laser Doppler flowmetry. Mean arterial blood pressure, heart rate and blood gas
      values were measured. Cutaneous blood volume, velocity and flow decreased
      significantly after drawing 10 mL/kg of blood, while heart rate, mean arterial
      blood pressure and blood gas did not change. The decrease of cutaneous blood
      velocity preceded that of blood volume and was associated more deeply with the
      reduction of blood flow. In conclusion, cutaneous microcirculatory monitoring
      using laser Doppler flowmetry is a sensitive technique for detecting early
      changes of circulatory failure caused by hemorrhage.

PMID- 8533586
TI  - Evaluation of rate-pressure product in obese children.
AB  - The purpose of this study was to evaluate the relationship between rate-pressure
      product (RPP) and degree of obesity in 511 obese 7 and 12 year old Chinese
      children. Obesity was assessed by anthropometry and skinfold thickness. The
      children were defined obese by relative weight (RW) > 120%. Bodyweight (W) and
      height (H) were used to derive body mass index (W/H2). Brachial systolic and
      diastolic pressures in these children were measured by cuff sphygmomanometry. RPP
      was calculated by the formula: heart rate x mean arterial pressure. More obese
      children (RW > or = 150%) had greater mean RPP (7 year old: 6389 vs 5976
      beats/min x mmHg, P < 0.05; 12 year old: 7024 vs 6686 beats/min x mmHg) than
      those with RW < 150%. Children in the upper 25 percentiles of RPP had
      significantly larger BMI (7 and 12 year olds) and RW (12 year olds), thicker
      biceps, triceps and subscapular skinfolds (12 year olds) (P < 0.01-< 0.05). The
      results indicate that RPP is, to some extent, related to the degree of obesity in
      obese children. The differences in RPP may imply varying degrees of hemodynamic
      stress to the heart. Whether such differences may contribute to the long-term
      development of cardiovascular morbidity in more obese individuals is uncertain.

PMID- 8533587
TI  - Analysis of the circumstances of death of 56 children suffering from cancer:
      proposal for the development of terminal medicine in Japan.
AB  - In Japan terminal medicine for children dying from cancer has not yet been
      developed nor has a support system for home terminal care and bereaved families
      been established. We have analyzed our own experiences in these areas and
      researched the possibilities of establishing support systems. In the 16 years
      from 1978 to 1993, 56 children with cancer have been treated and have died at
      Hamamatsu University Hospital. We analyzed the circumstances of their deaths. We
      interviewed 25 sets of parents about their acceptance of their child's death.
      Three children (5%) died unexpectedly during treatment, 27 children (48%) died
      from the side-effects of intensive treatment, and 26 children (47%) died during
      terminal care. More children with leukemia and lymphoma died from side-effects
      than children with solid tumors (P < 0.05). Six out of the 25 families had not
      yet accepted the loss of their child due to regrets associated with the missed
      opportunity for terminal care. From our experiences with the five children who
      received terminal care at home, we recognize the need for a support system run by
      the hospital and conclude the time is ripe for initiating home-based terminal
      care in Japan.

PMID- 8533589
TI  - Length polymorphism of heterochromatic segment of the Y chromosome in boys with
      acute leukemia.
AB  - The extent of length polymorphisms of the heterochromatic and euchromatic segment
      of the human Y chromosome were investigated in 15 boys with acute leukemia and
      were compared with 15 normal controls. A greater value of the Yh/F index in
      relation to controls was established (P < 0.05). The length of the euchromatic
      segment was also shorter in the patients than the controls (P < 0.05).

PMID- 8533588
TI  - Effect of cyclosporin A on human bone marrow granulocyte-macrophage progenitors
      with anti-cancer agents.
AB  - Cyclosporin A (CyA) overcomes P-glycoprotein (P-gp) associated multidrug
      resistance (MDR). P-gp expression is frequently observed among, not only various
      cancer cells, but also several normal tissues including bone marrow progenitor
      cells. These findings lead us to examine whether CyA enhances the myelotoxicity
      of anti-cancer agents. Bone marrow mononuclear cells were incubated with anti
      cancer agents (vincristine, VCR; doxorubicin, ADM; etoposide, VP-16; cytarabine,
      Ara-C; methotrexate, MTX) and a concentration of CyA (0.5, 5.0 micrograms/mL).
      The methylcellulose assay for granulocyte-macrophage progenitors (CFU-GM) was
      conducted using the post-treated cells. There was no significant toxicity for
      marrow CFU-GM formation after 72 h incubation with CyA (84-108% of control). The
      inhibitory concentration that reduced colonies by 50% (IC50) was 12 nmol/L for
      VCR, 6 nmol/L for ADM, 220 nmol/L for VP-16, 15 nmol/L for Ara-C and 35 nmol/L
      for MTX, respectively. For VCR, ADM and VP-16, the number of CFU-GM was unchanged
      with the addition of CyA at 0.5 microgram/mL concentration. In contrast at 5
      micrograms/mL CyA, the number of CFU-GM (% of control) was reduced significantly
      (P < 0.05 or P < 0.01). With MTX and Ara-C, the number of CFU-GM was unchanged
      after addition of CyA, even at 5 micrograms/mL concentration. We conclude CyA may
      therefore enhance cytotoxic drug sensitivity in MDR tumor cells at a clinically
      achievable concentration (0.5 microgram/mL) without marrow toxicity.

PMID- 8533590
TI  - Intra-abdominal fat in obese children.
AB  - We investigated the distribution of abdominal fat accumulation in obese children
      to know whether a clustering of coronary risk factors was demonstrated in
      visceral fat obesity as reported in adults. The relative indicator of intra
      abdominal fat accumulation was obtained from computed tomography scans at the
      umbilicus level in 36 obese subjects (24 males, 12 females). There was no
      visceral fat obesity in this study by reported criteria. All metabolic variables
      except triglyceride did not correlate significantly with intra-abdominal fat
      accumulation. We conclude that visceral fat obesity is a rare status and has no
      close relationship to coronary risk factors in childhood.

PMID- 8533591
TI  - The relationship between serum transaminase activities and fatty liver in
      children with simple obesity.
AB  - To determine hepatic diseases in obese children, biochemically and
      histologically, 11 obese patients with abnormal serum transaminase activities
      were subjected to this study. Fat accumulation in the liver was
      semiquantitatively graded, and histologically the 11 patients were classified
      into four groups; fatty liver, fatty hepatitis, fatty fibrosis and fatty
      cirrhosis. All patients had fat deposition in liver specimens, the grade of which
      did not significantly correlate with the degree of obesity. The grade of fat
      deposition in the liver specimens also did not significantly correlate with
      either serum transaminase activities or GOT/GPT ratio. Five patients were grouped
      into the fatty liver group, three into the fatty hepatitis group, and the
      remaining three patients into the fatty fibrosis group. However, no significant
      differences were found among the three histologically classified groups in terms
      of serum transaminase activities or GOT/GPT ratio. The usefulness of serum
      transaminase activities and GOT/GPT ratio was limited in predicting the severity
      of fat deposition or histological abnormality in pediatric obese patients.

PMID- 8533592
TI  - Pulse methylprednisolone therapy in children with membranoproliferative
      glomerulonephritis.
AB  - The effects of pulse methylprednisolone (PM) therapy were studied in 15 patients
      (aged 3-14 years) with biopsy proven membranoproliferative glomerulonephritis
      (MPGN). Patients were treated with intravenous PM 30 mg/kg (max 1 g) given over
      30 min every other day for a mean of 9.8 days (3-15 days). Oral prednisolone
      therapy was continued at a dose of 1 mg/kg/24 h for 1 month and subsequently
      tapered off the following month. Eight patients had hematuria and six had
      medically controlled hypertension. Serum C3 levels were low in 11 patients and
      all of the patients had proteinuria. Following PM therapy proteinuria was
      significantly reduced from 2602.9 +/- 1852.5 mg/24 h to 1871.2 +/- 2090.8 mg/24 h
      (P < 0.05) and at final evaluation, proteinuria was 774.33 +/- 1225.67 mg/24 h
      which was significantly lower than pre- and post-PM therapy values (P < 0.05).
      Serum creatinine levels were high in five patients before PM therapy and remained
      high in one of the patients who progressed to end-stage renal failure. After PM
      therapy, high serum creatinine levels normalized in three patients and was
      reduced, but still above normal, in one. One patient, with initially normal serum
      creatinine, had elevated levels afterwards. Nine of the patients were considered
      responsive and six non-responsive according to our tentatively defined criteria.
      Mean follow-up period was 27.4 +/- 24.1 months (6-84 months). Three patients were
      lost for follow-up, and 12 were re-evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533593
TI  - Pancreatic ascites in children.
AB  - We report on three children with pancreatic ascites confirmed by endoscopic
      retrograde cholangiopancreaticography (ERCP) and treated with surgery. The
      children presented with ascites, malnutrition and severe weight loss. Pancreatic
      ascites was diagnosed by elevated ascitic fluid and serum amylase levels. ERCP
      demonstrated a pseudocyst and the site of disruption of the pancreatic duct, but
      not the etiology of the pancreatitis. Following a period of nutritional support,
      surgery was carried out. Two of the children underwent a stented transgastric
      drainage of the pseudocyst; a recurrent pseudocyst in one of the children
      required a revision cystojejunostomy. The third child was treated with a Roux-en
      Y cystojejunostomy. All the children are pain-free and without ascites and are
      doing well on long-term follow-up. We conclude that pancreatic ascites must be
      considered in the differential diagnosis of intractable ascites in children. An
      ERCP is essential in planning management and cystoenterostomy is the definitive
      treatment.

PMID- 8533594
TI  - Congenital hypothyroidism with delayed rise in serum TSH missed on newborn
      screening.
AB  - We report on a female patient with congenital hypothyroidism (CH) missed on a
      newborn screening test. She is now 10 years old with retarded development. The
      patient was born premature at 34 weeks of gestation with birth-weight of 1515 g,
      and was judged to be normal in the screening programme of Niigata Prefecture.
      However, she gradually suffered from poor weight gain and retarded development
      with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were
      rechecked and showed high values with normal T3 and T4 levels. She was referred
      to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic
      thyroid) with a delayed rise in blood TSH concentration, probably due to the
      prematurity of the hypothalamic-pituitary-thyroid axis. L-thyroxine therapy
      brought a decline in TSH levels with partial improvement of her symptoms.
      Regardless of the result of newborn screening, infants with elevated serum TSH
      levels should be carefully examined for possible CH, even when T3, T4 and free T4
      values are in the normal range.

PMID- 8533595
TI  - Atypical hemolytic uremic syndrome.
AB  - The pathogenesis of atypical uremic syndrome (HUS), which is rarely encountered
      in childhood, is poorly understood and its mortality and morbidity rates are
      high. A wide variety of therapeutic approaches has been attempted and the
      literature contains numerous conflicting reports about the results of these
      approaches. In a case diagnosed as recurrent atypical HUS, pulse methyl
      prednisolone, fresh frozen plasma infusions and plasma exchange transfusion were
      used at different stages of the disease with satisfactory response.

PMID- 8533596
TI  - Acute renal failure after exercise in a child with renal hypouricemia.
AB  - We describe a 15 year old boy with renal hypouricemia who developed acute renal
      failure after a school athletics meeting, accompanied by appendicitis. During
      acute renal failure, the highest level of uric acid was 5.0 mg/dL, creatinine 7.9
      mg/dL and urea nitrogen 58.6 mg/dL. After recovery, the serum uric acid fell to
      0.9 mg/dL and the fractional excretion of uric acid (FEuA) exceeded the normal
      range. The probenecid and pyrazinamide tests showed that the patient had a total
      defect of uric acid reabsorption. This case suggested that strenuous exercise
      could be responsible for acute renal failure in patients with renal hypouricemia.

PMID- 8533597
TI  - Cardiac hydatid cyst in a child: diagnostic value of echocardiography and
      magnetic resonance imaging.
AB  - Cardiac hydatid cyst is extremely rare in children. We report a case of a cardiac
      echinococcal cyst in an 11 year old boy, diagnosed by two-dimensional
      echocardiography and magnetic resonance imaging (MRI). The cyst was located in
      the posterior wall of the left ventricle and was excised surgically.
      Echocardiographic and MRI findings are discussed.

PMID- 8533598
TI  - Herpes zoster in a normal child after varicella vaccination.
AB  - A healthy 5 year old girl developed herpes zoster in the dermatome supplied by
      the ophthalmic branch of the fifth cranial nerve 40 months after varicella
      vaccination. She was admitted to our hospital because of high fever and painful
      vesicular lesions over the left side of her forehead. She was treated
      successfully with systemic and topical acyclovir without developing herpetic
      keratoconjunctivitis. Our acute and convalescent phase evaluations showed that
      non-specific cellular and humoral immunity was normal. This is the fourth case of
      herpes zoster developing in an immunocompetent child following vaccination.
      Unlike the previously reported cases, our patient required hospitalization mainly
      to prevent ocular involvement. The issue concerning whether the universal
      introduction of varicella vaccination of normal children will reduce the
      incidence of the subsequent occurrence of herpes zoster must await further
      studies involving longer follow-up periods.

PMID- 8533599
TI  - Long-term sequential changes of antibody to p40tax in HTLV-I carrier mothers and
      children.
AB  - Antibody to p40tax (anti-p40tax) in serum specimens obtained sequentially from a
      human T cell lymphotropic virus type I carrier population of mothers and children
      were assayed. The prevalences of anti-p40tax at the initial sampling were 88%
      (7/8) in children and 55% (16/29) in mothers. Two of the seven positive children
      lost their anti-p40tax during the investigation period, resulting in a final
      prevalence of 63% (5/8) in children. However, anti-p40tax status was constant in
      all the 22 mothers with multiple serum samples (15 remained positive and seven
      remained negative). A decline in the absorbance value of EIA for anti-p40tax was
      observed in seven of the 15 anti-p40tax positive mothers. This decline may result
      in the disappearance of anti-p40tax in some of them.

PMID- 8533600
TI  - Chemiluminescent immunoassay (CLIA) for the detection of brucellosis and
      tularaemia antigens.
AB  - The detection of brucellosis and tularaemia infection agents is of particular
      interest for medical practice. The possibility of using enhanced
      chemiluminescence reactions for the determination of these agents is studied in
      this work. Light intensity depends on both the conjugate concentration used and
      the conditions at which the adsorption was performed. Optimal conditions for
      these test-systems were: approximately 20 micrograms/mL of Ig and 200
      micrograms/mL (titre 1:20) of conjugate. As is seen from the chemiluminescent and
      spectrophotometric results the lowest determined concentrations are 10 and 30
      ng/mL (for brucellosis) and 1 and 5 ng/mL (for tularaemia), respectively.
      Calibration curves in the antigen concentrations ranging from 10 to 2500 ng/mL
      (for brucellosis) and from 1 to 500 ng/mL (for tularaemia) are observed. Optical
      density depends linearly on the logarithm of the antigen concentration from 30 to
      5000 ng/mL (for brucellosis) and from 5 to 250 ng/mL (for tularaemia). The
      results obtained permit the conclusion that the chemiluminescence method can be
      used in enzyme immunoanalysis for brucellosis and tularaemia antigens.

PMID- 8533601
TI  - A blue chemiluminescence in the reaction of umbelliferone with hypochlorite.
AB  - A strongly fluorescing 7-hydroxycoumarin (umbelliferone, U) oxidized in dilute
      (10 mumol/L-O, 1 mol/L) aqueous solution with CIO- or CIO- + H2O2 (but not with
      H2O2 alone) produces a strong chemiluminescence (CL). Light emission kinetics
      depends on the pH of solution (4.0-10.5) and the reaction has a low activation
      energy Ea = 31 +/- 2 kJ/mol (285-310 K). The spectrum covers the fluorescence of
      umbelliferone (400-550 nm, lambda max 460 nm). No red emission typical of 1 delta
      g, 1 sigma g, 1 sigma+g (O2)2 is observed either in the umbelliferone+CIO- or the
      umbelliferone +CIO- + H2O2 solution. The possible mechanism of CL and concomitant
      degradative oxidation of umbelliferone is discussed.

PMID- 8533602
TI  - A novel bioluminogenic assay for alpha-chymotrypsin.
AB  - The use of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin as a novel substrate for
      alpha-chymotrypsin has been demonstrated. The kinetic parameters determined are
      KM = 0.38 mmol/L, kcat = 6.5 s-1 and kcat/kM = 17,100 (L/mol s). The test
      principle of the coupled assay is the release of aminoluciferin by enzymatic
      cleavage of 6-(N-acetyl-L-phenylalanyl)-aminoluciferin. Aminoluciferin is
      oxidized, with light emission, by firefly luciferase (Photinus pyralis) and can
      be quantified in a luminometric assay. The detection limit for chymotrypsin was
      found to be 0.3 ng per assay. 6-(N-acetyl-L-phenylalanyl)-aminoluciferin has been
      synthesized as an example for a new class of highly sensitive substrates. By
      modification of the peptide residue these new substrates may be suitable for
      ultrasensitive detection of different proteinases.

PMID- 8533603
TI  - The development of Luminomaster, a fully automated chemiluminescent enzyme
      immunoassay system.
AB  - We have developed a fully automated discrete chemiluminescent heterogeneous
      enzyme immunoassay system called Luminomaster. The characteristics of this
      analyser are: 120 test/h throughput, 14 test menu, wide dynamic range, automated
      sample dilution, automatic retest, communication with a host central processing
      unit (CPU) and connection with sample transfer system.

PMID- 8533604
TI  - Fast and sensitive chemiluminescence determination of H2O2 concentration in
      stimulated human neutrophils.
AB  - A fast and sensitive chemiluminescence assay for the determination of H2O2 in
      stimulated neutrophils without the use of enzymes was developed. The method is
      based on the oxidation of luminol by hypochlorous acid. The chemiluminescence of
      this reaction is highly dependent on the concentration of hydrogen peroxide.
      Changes in H2O2 concentration in PMA-stimulated neutrophils were followed by
      injection of NaOCI to cell suspension at different times after cell stimulation.
      The short integration time of 2 s permits calculation of actual concentrations of
      H2O2 without influence of H2O2 decomposition by cellular enzymes or newly
      produced H2O2 due to dismutation of superoxide anion radicals. Concentrations of
      H2O2 were diminished by catalase and enhanced by sodium azide owing to inhibition
      of cellular catalase and myeloperoxidase. Changes in H2O2 concentration upon
      stimulation could be observed at 3000 cells/mL.

PMID- 8533605
TI  - A comparative study of PCR product detection and quantitation by electro
      chemiluminescence and fluorescence.
AB  - Amplification and detection of target DNA sequences are made possible in a
      polymerase chain reaction (PCR) by using a mixture of biotinylated and
      ruthenium(II) trisbipyridal (Ru(bpy)3(2+))-end-labelled primers. In this way,
      biotin for capture and Ru(bpy)3(2+) for detection are directly incorporated into
      the PCR product obviating subsequent probe hybridization. PCR of a bacterial DNA
      template from Alteromonas species strain JD6.5 using a cocktail of biotin- and
      Ru(bpy)3(2+)-labelled primers amplified a 1 kilobase region. Serial dilution of
      PCR product followed by magnetic separation with Streptavidin (SA)-coated
      magnetic beads and an electrochemiluminescence (ECL) assay using the semi
      automated QPCR System 5000 demonstrated sensitive (pg range) DNA detection. ECL
      assay of probe hybridization to a human immunodeficiency virus (HIV) sequence
      also produced pg level sensitivity. Quantitative DNA determination by ECL assay
      correlated well with visual detection of DNA in electrophoretic gels. However,
      DNA detection by ECL assay was 10 to 100 times more sensitive than conventional
      ethidium bromide staining. The combination of DNA-based magnetic separation with
      ECL assay provides a very sensitive and rapid method of quantitating DNA which,
      owing to its rapid and facile nature, may have many applications in the research,
      environmental monitoring, industrial and clinical fields.

PMID- 8533606
TI  - Comparison of seven bio- and chemiluminescent reagents for in situ detection of
      antigens and nucleic acids.
AB  - Bio- and chemiluminescence have proved sensitive enough to compete with
      chromogenic and radioisotopic tracers for in situ detection. However, they must
      also provide a discriminant morphological analysis of the specific signal. We
      have tested seven bio- or chemiluminescent reagents for tissue antigen and
      nucleic acid detection by immunocytochemistry (ICC) or in situ hybridization
      (ISH). They were based on luminescent detection of peroxidase, alkaline
      phosphatase, beta-galactosidase or xanthine oxidase. We also explored whether
      high molecular weight polymers could increase the spatial definition of the
      photon emission. An ICCD camera was used to collect the light signal provided by
      immunolabelling of endothelial cells and by ISH of human papilloma virus on cell
      smears. Among the enzyme-luminescent substrate combinations tested, the enhanced
      luminol chemiluminescence (ECL) gave the best resolution of the specific signal.
      The other systems were mainly hampered by a high diffusion of the reaction
      product over the tissue section. Unfortunately, in this case, the high molecular
      weight polymers tested were inefficient. However, the addition of
      polyvinylalcohol (PVA) or polyvinylpyrrolidone (PVP) significantly improved
      respectively the definition and intensity of ECL photon emission. We demonstrate
      that chemiluminescence gives a morphological resolution allowing histological
      examination. The extension of this new application, now depends on
      physicochemical adaptation of chemiluminescent reagents to the constraints of
      tissue detection.

PMID- 8533607
TI  - Action of phenolic antioxidants on various active oxygen species.
AB  - The action of phenolic antioxidants, such as probucol, on various active oxygen
      species was investigated using luminol chemiluminescence and spin trapping with
      5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The various active oxygen species,
      including hydroxyl radicals (Fenton reaction), superoxide anions, singlet oxygen
      and hypochlorite ions were examined with phenolic antioxidants under aqueous and
      nonaqueous conditions. Probucol showed a quenching effect on both superoxide
      anions and hypochlorite ions in nonaqueous solution. However, it had no effect on
      hydroxyl radicals. alpha-Tocopherol, a natural phenolic antioxidant, showed a
      stronger quenching effect on superoxide anions and hypochlorite ions than
      probucol, and quenched hydroxyl radicals in nonaqueous solution. Furthermore,
      Trolox showed a quenching effect on all active oxygen species in both aqueous and
      nonaqueous solution. The antioxidants were studied under comparable conditions in
      a series of test systems and the reactivity profiles depicted as 'radar charts'
      which are helpful for characterizing antioxidant action.

PMID- 8533608
TI  - Monitoring of spatial expression of firefly luciferase in transformed zebrafish.
AB  - The firefly luciferase gene attached to the cytomegalovirus promoter was
      transferred into zebrafish (Brachydanio rerio) by microinjection of fertilized
      eggs. Light emission could be monitored in vivo in eggs and throughout the early
      development of the fish by low-light video-image analysis. Gene expression was
      transient in most of the cases lasting for about 2 weeks. This gene cassette
      proved to be a very convenient and non-destructive transformation marker and the
      firefly luciferase gene appears to be a powerful tool for real-time imaging of
      tissue-specific gene expression in transgenic fish.

PMID- 8533609
TI  - Light from Maillard reaction: photon counting, emission spectrum, photography and
      visual perception.
AB  - Several authors have reported on high-sensitivity measurement of oxygen-dependent
      low-level chemiluminescence (CL) from Maillard reactions (MR), i.e. nonenzymatic
      amino-carbonyl reactions between reducing sugars and amino acids (also referred
      to as nonenzymatic browning). Here we report for the first time, that light from
      Maillard reactions can be seen by the human eye and also can be photographed. In
      parallel with visual perception and photography CL was monitored by means of a CL
      detection programme of a liquid scintillation counter (LSC, single photon rate
      counting). CL emission spectrum was recorded by a monochromator-microchannel
      plate photomultiplier arrangement. CL intensity from reaction of 6-aminocaproic
      acid with D-ribose (200 mg each) in 5 mL H2O at pH 11 at 95 degrees C was high
      enough for visual perception after adaptation to absolute darkness. Reaction in
      dimethylsulphoxide (DMSO) exhibited strongly enhanced CL (10 mg each in 5 mL were
      sufficient for visual detection) and could be photographed (15 minutes' exposure,
      ASA 6400); all characteristics of Maillard specific CL (O2-dependence, no CL from
      nonreducing sugars, inhibition by sulphur compounds) remained. Visual detection
      of CL and measurement by LSC were in full concordance. The CL emission spectrum
      showed two broad peaks at around 500 nm and 695 nm. Fluorescence emission of the
      brown reaction mixture matched the blue-green part of the CL emission spectrum.
      Emission of visible light during Maillard reactions may partly originate from
      oxygen-dependent generation of excited states and energy transfer to
      simultaneously formed fluorescent products of the browning reaction.

PMID- 8533610
TI  - Assay of cholinesterase using a pro-enhancer of the luminol-H2O2-horseradish
      peroxidase reaction.
AB  - 2-Naphthyl acetate acts as a pro-enhancer of the luminol-H2O2-horseradish
      peroxidase reaction. Cholinesterase hydrolyses the bound acetyl group and
      produces 2-naphthol, and this compound is an enhancer of the chemiluminescent
      reaction. We studied the kinetics of chemiluminescent emission and the influence
      of 2-naphthyl acetate and cholinesterase enzyme concentrations. The
      cholinesterase concentration versus chemiluminescence intensity maximum was
      linear for cholinesterase between 0 and 181 microU/mL, with a detection limit of
      8 microU/mL and a relative standard deviation of 9.5% (n = 3), for a sample
      containing 90.67 microU/mL of cholinesterase.

PMID- 8533612
TI  - Bioluminescence and chemiluminescence literature. The 1994 Literature: Part 3.

PMID- 8533613
TI  - [Job satisfaction in physicians with a career in general clinical medicine].
AB  - An inquiry was sent to Portuguese G.P.s all over the country, in order to
      characterize their professional satisfaction. Through 41 questions, divided into
      11 different areas, several factors of satisfaction concerning their work in
      Health Centers were analyzed, such as working conditions and the professional
      team work relationship, as well as salaries. According to the results, we may
      conclude that there is a general deep dissatisfaction among these G.P.s, and a
      great percentage of them declared they would even change their career if
      circumstances allowed them.

PMID- 8533611
TI  - Enumeration of phagocytosed Staphylococcus aureus inside cells of the mouse
      macrophage cell line J774 by bioluminescence, fluorescence and viable counting
      techniques.
AB  - In order to quantify intracellular Staphylococcus aureus within a macrophage-like
      cell line by a bioluminescence technique, the mouse cell line J774 and opsonized
      Staphylococcus aureus were incubated together to allow phagocytosis to occur.
      Experiments using UV microscopy and fluorescent stained S. aureus were performed
      to determine an estimate of the mean intracellular bacterial numbers. For
      enumeration of intracellular bacteria by a bioluminescence technique,
      extracellular bacteria were removed by washing, the macrophages lysed
      mechanically and osmotically and treated with apyrase to remove somatic ATP.
      Bacterial cells were washed and the intracellular ATP measured by firefly
      luciferase bioluminescence in a luminometer. This new method of enumerating
      intracellular bacteria was compared to the conventional method of viable counts
      and found to correlate (r = 0.78). The bioluminescence assay developed was found
      to be a relatively rapid alternative method to the techniques currently used to
      enumerate intracellular bacteria and could prove advantageous in studies of
      intracellular killing and effects of antimicrobial agents on intracellular
      pathogens.

PMID- 8533614
TI  - [Tubo-ovarian abscess. An analysis of 20 cases].
AB  - The authors make a 3-year retrospective analysis of the tubo-ovarian abscess
      cases admitted to the Gynecology Ward of Dr Alfredo da Costa Maternity Hospital.
      In the period studied (1991 through 1993) there were 20 such cases. The incidence
      in nulliparous patients was 25%. A significant percentage (30%) of the patients
      had recently undergone uterine instrumentation. A prior history of pelvic
      inflammatory disease was obtained in only 15% of the cases. In the IUD users the
      incidence of unilateral and bilateral abscesses was identical. Most patients
      (85%) became apyretic within 48 hours of instituting intravenous antibiotics. In
      most cases (90%) the patients underwent surgical therapy. The mean time elapsed
      between instituting antibiotics and the surgical procedure was 3 days. There was
      one case of intra-abdominal rupture of the abscess. Intraoperatively, an
      appendiceal abscess was found in 3 (15%) patients. In 30% of the cases a total
      hysterectomy with unilateral or bilateral adnexectomy was performed. One of the 2
      (10%) patients treated solely with medical therapy presented abscess recurrence
      one month after hospital discharge. Although the management of tubo-ovarian
      abscesses has become more conservative it still includes, in most cases, surgical
      drainage or extirpation after appropriate antibiotic therapy.

PMID- 8533615
TI  - [The use of serological tests for detecting HIV infection in general clinical
      consultations and hospital consultations].
AB  - AIMS: To determine the number and type of HIV tests requested in general practice
      (GP) and in hospital outpatient clinics, to identify principle risk behaviors, to
      determine the percentage of HIV positive tests and to identify possible factors
      associated with the request of HIV tests. METHODS: Cross-sectional, analytical
      and observational study, involving 80 GPs and 45 hospital specialists in the
      region of Lisbon. All requests for HIV tests were analysed during a 12 month
      period. RESULTS: 936 HIV tests were requested, with a mean of 12.47 in GP and
      0.69 in the hospital. Risk behaviors observed were mainly heterosexual contacts
      and intravenous drug abuse (IVDA). The motives of the requests mainly were
      pregnancy, risk behaviors in GP and the presence of symptoms suggesting HIV
      infection in the hospital. The initiative of the request came from doctors in 70%
      of the cases. The percentage of HIV positive tests (ELISA + Western blot) was
      4.2% in GP and 32% in the hospital. According to risk behaviors, the percentage
      of seropositivity was 33% in homo/bisexuals, 13% in IVDA, 7% in heterosexuals
      with risk behaviors and 0.2% in individuals with unidentified risk behaviors.
      CONCLUSIONS: The patterns of request of HIV tests differ in hospital and in GP.
      In a significant percentage of cases, no informed consent was obtained prior to
      HIV testing, both in hospital and GP. This study may serve as an indicator of the
      need for information and education programs concerning HIV testing directed to
      health professionals and the general population.

PMID- 8533616
TI  - [The course of care for cancer patients hospitalized in a central hospital].
AB  - Prevention and early diagnosis are considered the main tools to reduce the
      incidence and mortality from cancer. The authors studied prospectively 150
      oncologic patients admitted to Santa Maria Hospital-Lisbon from April/92 to
      April/93, by personal interview, to analyze their assistance pathways from the
      appearance of first symptoms. We tried to define the role of the different
      medical assistance structures and the most important factors conditioning delay
      in diagnosis and therapeutics. The results show that primary care physicians were
      the first medical assistance in 56% of patients; 22% of the patients went to the
      Emergency Service of the Hospital for the first time. Duration of symptoms was
      less then 3 months in 74% of the population studied. Primary care physicians
      diagnosed neoplasia in 32% of the cases and prescribed symptomatic treatment in
      another 41%. The Emergency Service was the most efficient in diagnosis, providing
      rapid orientation in 91% of patients. In this population, 43% had their residence
      more than 30 km from Lisbon. Median age was less than 60 years. These results
      emphasize the fundamental role of Primary Care Physicians in the initial
      management of cancer patients and their responsibility in early diagnosis. They
      also suggest the need for the promotion of graduate education and courses
      designed for primary care physicians and the population.

PMID- 8533617
TI  - [Tuberculosis in Portugal].
AB  - There is a general downward trend of most epidemiological indices for TB, except
      for mortality. Incidence and prevalence rates were, for the first time ever,
      situated below 50 cases/100,000 inhabitants and smear-positive cases below
      25/100,000. TB occurs mostly in the large, coastal cities, Lisboa and Oporto
      having 50% of the cases. There is a decreasing trend in 14 districts. Males are
      most affected. Young adults, 19 to 44 years old are the most prevalent group,
      children under 15 having very few cases and hardly any cases of miliary or
      meningitis. TB occurring together with AIDS had a greater increase than AIDS
      alone. Substance abusers had a greater increase of both situations, as well as
      deaths, than the other risk groups. BCG vaccination, as part of EPI, attained 91%
      coverage of newborns.

PMID- 8533618
TI  - [The neurochemical aspects of Alzheimer's disease].
AB  - Alzheimer's disease is one of the most severe and most common progressive
      neurodegenerative diseases of ageing. It accounts for a significant number of
      cases of senile dementia. It is a major health problem, considering the current
      increase in the geriatric population all over the world. The purpose of this
      article is to review the neurochemical and histopathological aspects of
      Alzheimer's disease as well as the most recent therapeutical advances in this
      area.

PMID- 8533619
TI  - [Growing old at the end of the 20th century. The challenge to gerontology and
      geriatrics].
AB  - This article concerns teaching and training in medical geriatrics and
      gerontology. A synoptic overview of this subject in developed countries is
      presented. The author discusses the best curriculum for Portugal, in her opinion,
      concerning the pre- and postgraduate teaching and training in gerontology and
      medical geriatrics.

PMID- 8533620
TI  - [Pleural effusion of non-neoplastic etiology in a patient with a rare form of
      myeloma].
AB  - Pleural effusions can be a manifestation of several nosological entities.
      Etiologic diagnosis involves a good clinical history, followed by thoracocentesis
      with pleural biopsy and eventually bronchoscopy or thoracoscopy. The
      differentiation between transudates and exudates, by the biochemical
      characteristics of the pleural effusions, can orientate the underlying disorder.
      It is known that there are more than 35 different etiological entities of
      exudative pleural effusions. However, pneumonia, malignancies, pulmonary
      embolism, abdominal disease and tuberculosis are the major causes (around 90%).
      Transudative effusions are more frequently due to congestive heart failure, renal
      or hepatic failure. The AA present a clinical situation of pleural effusion, the
      etiology of which was initially attributed to congestive heart failure, with a
      good response, clinical and radiological response to the treatment established.
      However the laboratory alteration persisted (anaemia, renal failure, acute
      inflammation). The subsequent study showed the existence of a rare syndrome, a
      Myeloma Ig M lambda that can lead to differential diagnosis with Waldenstrom's
      Macroglobulinemia, about which the authors make some theoretical considerations
      showing the difficulty in etiologic diagnosis of some pleural effusions.

PMID- 8533621
TI  - [Primary malignant neoplasms of the female genitalia].
AB  - A patient with synchronous multiple malignant neoplasms of the female genital
      tract, involving the ovary, the cervix and the endometrium is described. A 49
      year-old patient, presenting pelvic pain and menometrorrhagia over the last six
      months. An abdominal and speculum examination revealed an abnormal mass occupying
      the entire left lower quadrant and a vegetating tumor of the cervix,
      respectively. Microscopic examination of the uterus and ovary revealed a
      cystadenocarcinoma of the ovary and an adenosquamous carcinoma of the cervix and
      an endometrioid carcinoma of the endometrium. The data suggests this is a
      multiple mullerian tumor. Due to treatment and prognostic implications, in the
      presence of a patient with a tumor involving different organs, we must not
      overlook differential diagnosis between primary and metastatic tumor.

PMID- 8533622
TI  - [A false incisional hernia during coumarin anticoagulation].
AB  - This short clinical report presents a case of giant pelvic hematoma with
      infiltration of the abdominal wall, initially misdiagnosed as incisional hernia
      by means of the old McBurney laparotomy. The patient, a 56-year-old female, was
      under chronic coumarin anticoagulation to prevent systemic embolism recurrence
      (rheumatic polyvalvular disease, atrial fibrillation, and previous brain
      embolism). On admission, the I.N.R. was 6.6. The risks versus benefits dilemma of
      chronic oral anticoagulation is briefly commented.

PMID- 8533623
TI  - A review of safety, efficacy, pros and cons, and issues of puerperal tubal
      sterilization--an update.
AB  - This review focuses on the safety, efficacy, pros and cons of tubal sterilization
      procedures performed during the puerperium period while the woman is still in
      hospital. Findings from four previous reviews are synthesized, and the results
      published in more recent literature are evaluated. The review finds that tubal
      sterilization performed while the woman is still on the delivery table, or during
      a woman's early puerperium while she remains hospitalized, is operationally easy
      and medically safe, and does not adversely affect lactation. However, reported
      pregnancy rates are generally higher in puerperal tubal sterilization than in
      interval sterilization, especially when the mechanical tubal occlusion technique
      is used. The Pomeroy method, and its modifications via minilaparotomy, is highly
      recommendable. On the other hand, electrocoagulation via laparoscopy is
      associated with high efficacy, but a potentially increased risk of complications
      and difficulties in tubal reversal. Tubal sterilizations can be easily and safely
      performed at cesarean delivery in selected cases. Tubal sterilization performed
      during puerperium has a number of advantages over short-acting contraceptive
      methods, which require strict compliance, for postpartum use. However, candidates
      for puerperal tubal sterilization need to be carefully screened and counseled,
      since post-sterilization regret is more likely to occur. Unsettled issues for
      puerperal tubal sterilization and a number of practical problems that need to be
      addressed before initiation of a puerperal tubal sterilization program in a
      maternity clinic/hospital are discussed.

PMID- 8533624
TI  - A single-dose and 3-month clinical-pharmacokinetic study with a new combination
      oral contraceptive.
AB  - The study was performed in 14 young women. The combination oral contraceptive
      contained 75 microgram gestodene (GSD) and 20 microgram ethinyl estradiol (EE2)
      per dosage unit. The volunteers received a single dose on day 21 of a treatment
      free precycle (PCd21) and, after a washout period of 7 days, used the preparation
      in a 21 d/7 d schedule for three months. Daily drug serum level profiles were
      taken on PCd21 and on days 1 and 21 of treatment cycles 1 and 3. In addition,
      trough drug serum levels were followed every other day during treatment cycles 1
      and 3. Serum levels of GSD, EE2, CBG, SHBG and testosterone (T) were determined
      by means of specifically developed or commercially available RIAs.
      Pharmacokinetic evaluation was carried out with TOPFIT and parameters were
      evaluated for differences with the t-test. Main target variables were Cmax, tmax
      and AUC for EE2, GSD and unbound GSD on day 21, cycle 3 vs. PCd21. EE2
      pharmacokinetics were in agreement with a dose of 20 microgram/unit. Single-dose
      Cmax of 65 pg/ml and AUC of 612 pg h ml(-1) increased by 40-60% during treatment
      cycles as a result of accumulation EE2 induced basal SHBG (102nmol/L) and CBG (42
      microgram/ml) serum levels to about 220 nmol/L and 87 microgram/ml, respectively,
      at the end of treatment cycles 1 and 3. Serum T levels dropped to 50% of baseline
      levels during treatment cycles and free T concentrations were reduced by 60-70%.
      GSD pharmacokinetics at the end of treatment cycles 1 and 3 were different from
      single-dose pharmacokinetics. Single-dose Cmax of 3.5 ng/ml and AUC 0-24 h of 22
      ng h ml(-1) increased to steady-state levels of 8-8.7 ng/ml and 90-106 ng h ml(
      1), respectively. The increase in GSD levels under treatment is the result of two
      parallel processes, i.e. accumulation and enlargement of the specific binding
      compartment. This was shown by protein-binding experiments, demonstrating an
      increase in specific (SHBG) binding from 69% to 80% and a reduction in the free
      fraction of GSD by 40% during treatment. The results of GSD and EE2
      pharmacokinetics obtained in the present study confirm previous results with
      Femodene, when the reduction in the EE2 dose by 10 microgram/d is taken into
      account.

PMID- 8533625
TI  - The effects of two phasic oral contraceptives on hemostasis and platelet
      function.
AB  - OBJECTIVE: To compare the effects on hemostatic parameters of a combiphasic oral
      contraceptive containing desogestrel and ethinyl estradiol (DSG/EE) and a
      triphasic oral contraceptive containing levonorgestrel and ethinyl estradiol
      (LNG/EE). METHODS: In an open-label, randomized, group-comparative study in 10
      healthy volunteers per treatment group, the effects on parameters of coagulation,
      anticoagulation, fibrinolysis, antifibrinolysis and platelet function were
      determined at baseline, after three treatment cycles, and after a post-treatment
      cycle. Changes from baseline were analyzed using a paired t-test, whereas between
      group differences were analyzed by means of an analysis of co-variance. RESULTS:
      Both OC preparations induced modest changes of some coagulation, anticoagulation,
      fibrinolysis and antifibrinolysis parameters, although all mean values remained
      within the normal range. No significant effects were observed with either OC with
      respect to platelet function. Statistically significant differences between the
      two preparations could occasionally e observed: the concentrations of
      antithrombin II (AT-III) and Factor VII were higher with the DSG/EE preparation
      than with LNG/EE preparation at the end of treatment and AT-III activity, AT-III
      concentration, Factor X concentration, and plasminogen activity were higher with
      DSG/EE than with LNG/EE in the post-treatment cycle. CONCLUSIONS: Combiphasic
      DSG/EE and triphasic LNG/EE, both OCs with a comparable amount of EE per cycle,
      had no clinically significant effect on the overall hemostatic balance.

PMID- 8533626
TI  - A potential single insertion protocol for quinacrine pellet non-surgical female
      sterilization.
AB  - Two preliminary single-insertion clinical trials of the quinacrine pellet method
      of non-surgical female sterilization were compared. Both trials used
      transcervical application of quinacrine, 252 mg, and diclofenac, 75 mg, as
      pellets. In the first trial (21 April 1992 to 17 February 1993), 58 women
      received oral contraceptives for three months. In the second trial (19 February
      1993 to 25 May 1994), 229 women received medroxyprogesterone acetate, 150 mg IM,
      at the time of quinacrine insertion. At 18 months, the life-table pregnancy
      failure rate per 100 women of the first trial was 8.6 (SE 3.7), whereas the
      failure rate for the medroxyprogesterone acetate group was 0.5 (SE 0.5), p<0.05.
      There were no serious complications or side-effects in either group. Larger
      confirming trials with random allocation and long-term systematic follow-up are
      needed to determine whether a single injection of medroxyprogesterone improves
      the efficacy of quinacrine.

PMID- 8533627
TI  - Quality of care among Jamaican private physicians offering family planning
      services.
AB  - The National Family Planning Board is the agency of Government empowered to
      prepare, carry out and promote family planning programs in Jamaica. The Board has
      prioritized the expansion and sustainability of family planning services in large
      part through encouraging the participation of the private sector. To enhance the
      availability, acceptability and effectiveness of private physician family
      planning services, information was collected on the service practices of 90% of
      physicians, through face to face interviews. Bruce's framework was used to
      evaluate the findings of the study. The study indicated that: A wide variety of
      contraceptives are available - Basic equipment and adequate supplies are in place
      for the provision of services - Provider bias, inappropriate contraindicators and
      process and scheduling hurdles exist. The major recommendations relate to the:
      Revision of norms and guidelines for all contraceptives - Continuation of
      contraceptive technology updates for private physicians - Revision of
      legal/regulatory barriers which restrict access to some contraceptives for
      certain target groups.

PMID- 8533628
TI  - Materials, methods and results of the Norplant training program.
AB  - Norplant subdermal implants for contraception were introduced into UK clinical
      practice in October 1993. Use of Norplant requires providers to learn additional
      skills. A training program designed to give providers to opportunity to obtain
      these skills was designed and implemented through the co-operation of Hoechst
      Roussel, JHPIEGO and members of the UK medical profession. Uptake of training for
      Norplant provision has been widespread and Norplant has been established as a
      realistic contraceptive choice for women in the UK. Introduction of Norplant in
      the UK has raised many issues that go beyond clinical considerations.

PMID- 8533629
TI  - Contraceptive choice in Vigevano, Italy, 1983-1993.
AB  - The authors, after general consideration of family planning programs, present a
      study of 22714 women, who, in the decade 1983-1993, required contraceptive
      protection from the Family Planning Centers in the region of Vigevano (Italy).
      The authors underline the importance of a protocol used before beginning
      treatment to help prevent women receiving methods carrying too great a health
      risk. The results show a very high prevalence of oral contraception, increasing
      in recent years with the introduction of triphasic pills, while use of
      intrauterine contraception seems to be declining. Other conventional methods,
      such as barrier (diaphragm and condom) and 'natural' methods, had a low incidence
      in the sample studied. The reasons for these behaviors are analyzed and the
      relative trends discussed.

PMID- 8533631
TI  - [A morphological study of lymphocyte homing in conjunctiva-associated lymphoid
      tissue].
AB  - High endothelial venule (HEV) is an important component of the mucosa-associated
      lymphoid tissue and plays a role in the homing phenomenon of lymphocytes. We
      investigated the presence of HEVs in conjunctiva-associated lymphoid tissue
      (CALT) using guinea pigs sensitized with ovalbumin. Electron microscopy showed
      characteristic findings for HEVs in the parafollicular area of the CALT.
      Lymphocytes in the vessels are trapped not only by microprocesses extending from
      the vascular endothelium but also by the endothelial cells. Some endothelial
      cells also appear to release lymphocytes. We conclude that HEVs are present also
      in the CALT.

PMID- 8533630
TI  - [Cytokines in ophthalmology].

PMID- 8533632
TI  - [Anatomical evaluation of the anterior capsular zonular free zone in the human
      crystalline lens (age range, 50 approximately 100 years)].
AB  - It is important to determine the anterior capsular zonular free zone (ZFZ) in
      order to minimize the risk of zonular disinsertion. From this point of view the
      size of the ZFZ of normal suspended lenses was directly measured in 199 human
      eyes obtained postmortem. The cornea was completely excised and the iris removed
      to allow clear visualization of the anterior surface of the lens to the equator.
      After measuring lens diameter with a caliper, a 4 mm continuous curvilinear
      capsulorhexis was performed, and lens substrate was completely removed by
      phacoemulsification. Care was taken to minimize trauma to the zonules during
      surgery. The anterior insertion of the zonules was identified at high power
      magnification; the size of the ZFZ was measured with a caliper. The mean age was
      75.5 +/- 10.3 (+/-SD) years (age range, 50 approximately 100 years). The mean
      diameter of the lenses was 9.72 +/- 0.31 mm. The mean diameter of the ZFZ was
      6.83 +/- 0.35 mm. Statistical analysis revealed no significant correlation
      between the size of the ZFZ and age, or between the size of the ZFZ and lens
      diameter. The present study indicates that the size of the ZFZ was constant
      regardless of age or lens diameter.

PMID- 8533633
TI  - [The effects of dopa and oxygen on RNA concentrations in cultured chick embryonal
      retinal pigment epithelial cells].
AB  - We measured RNA and DNA concentrations in cultured chick embryonal retinal
      pigment epithelial cells to investigate the effects of dopa and oxygen on DNA and
      RNA synthesis. RNA/DNA ratios were decreased by addition of 250 microM dopa.
      Decrease of RNA/DNA ratios was suppressed when the oxygen concentrations were
      reduced from 20% to 10%. Incubation with medium containing 100 microM dopa
      increased RNA/DNA ratios in 10% oxygen. Exposure of retinal pigment epithelial
      cells to 250 microM dopa caused the decrease of RNA concentrations in the retinal
      pigment epithelial cells, which was ameliorated by lowering oxygen
      concentrations. However, the addition of 100 microM dopa in 10% oxygen stimulated
      retinal pigment epithelial cells and seemed to increase RNA concentrations.

PMID- 8533634
TI  - [Cell kinetics of rat lens epithelium by cytofluorometric nuclear DNA
      determination].
AB  - The cell kinetics of rat lens epithelium was assessed by measuring the changes in
      the nuclear DNA contents during sugar cataract formation. Six-and-12-week-old
      Sprague-Dawley male rats were used and divided into the following groups: fed on
      normal chow, fed on 25% galactose diet, and fed on normal chow after 5 days on
      the 25% galactose diet. Every second day following the beginning of each chow
      feeding, lenses were extracted, and lens capsules with epithelial cells were
      obtained. After a few day's fixation in 4% paraformaldehyde dissolved in 0.1M
      phosphate buffer (pH 7.4), DAPI (4'6-diamidino-2-phenylindole)-stained lens
      epithelial cells were measured by fluorescence cytophotometry. The epithelia in
      the normal chow-fed rats contained many 2C and a few 4C nuclei. In the 25%
      galactose-fed rats, 4C nuclei increased gradually in number until the fifth day,
      and then decreases slowly day by day. Abnormal polyploid nuclei (8C) were
      observed in the 25% galactose-fed rats. 4C nuclei decreased rapidly after the
      diet reversal. These results indicate that galactose feeding caused higher DNA
      synthesis of rat lens epithelial cells and a higher possibility of abnormal cell
      division.

PMID- 8533635
TI  - [The effect of subconjunctival injection of endothelin-1 on intraocular pressure
      in the rabbit].
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced in part by
      vascular endothelial cells. In order to investigate its effects on the episcleral
      vascular system and intraocular pressure (IOP), we injected ET-1 (3, 10, 30, 100,
      300, 1,000 pmol) into the subconjunctival space of rabbits and measured IOP with
      a manometer. Injection of a dose higher than 10 pmol caused a transient increase
      of IOP. Mean maximum elevation rate of IOP for each dose of ET-1 was 14.9 +/-
      0.9%, (mean +/- standard error) 43.5% +/- 9.5%, 40.8 +/- 7.5%, 46.9 +/- 9.8%, and
      84.1 +/- 22.6. Next, we injected 1,000 pmol into the subconjunctival space, and
      continuously measured IOP and ocular pulse pressure with a manometer. IOP
      increased rapidly after ET-1 injection. Maximal increase of IOP was observed at
      22.7 +/- 9.2 min after ET-1 injection, and IOP decreased after the peak. The
      ocular pulse pressure increased with IOP elevation and decreased with the IOP
      reduction. We speculated that the transient elevation of IOP was caused by
      increase of aqueous outflow resistance, and the decrease of IOP was caused by
      decrease of aqueous outflow resistance and decrease of blood flow in the ciliary
      body and the choroid. This strongly suggests that subconjunctival injection of ET
      1 could have a large effect on the episcleral vascular system, aqueous outflow,
      and blood flow in the ciliary body and the choroid.

PMID- 8533636
TI  - [Cytolysosomes in red blood cells of patients with Behcet's disease at the
      exacerbation stage].
AB  - Peripheral erythrocytes of 5 patients with Behet's disease, not receiving
      systemic treatment, at the exacerbation stage, and those of 3 healthy controls
      were investigated with a transmission electron microscope. More than 100 cells
      were examined per subject. Cytolysosomes (autophagic vacuoles) were frequently
      observed in cells of the patients. The average frequency of appearance of
      cytolysosomes was 5.4 +/- 1.5% (mean +/- deviation) in erythrocytes of the 5
      patients, and 0.5 +/- 0.4% in those of the 3 control subjects. The difference was
      statistically significant (p < 0.026). These results suggest that cytolysosomes
      of erythrocytes may reflect abnormal production or removal involved in the
      pathophysiology of Behcet's disease.

PMID- 8533637
TI  - [Dextromethorphan maintains the function of the detached retina].
AB  - In order to evaluate the effect of dextromethorphan (DEX), an antagonist of N
      methyl-D-aspartate receptors, on ischemic damage in the detached retina,
      transretinal electrical responses (trans-retinal electroretinogram: TR-ERG) to
      photic stimulation were recorded from the detached retina of rabbit eyes in
      vitro. In experiment 1, 0.1 ml of 0.1% DEX was injected into the subretinal space
      to produce retinal detachment (RD) of 8 mm diameter (DEX group). For the control,
      the same volume of Hanks' solution was injected instead of DEX (control group).
      In experiment 2, 0.1 ml of 0.1% DEX was dropped onto retina, and RD was produced
      by injecting 0.1 ml of Hanks' solution into the subretinal space (DEX group). For
      the control, the same volume of saline was dropped onto the retina instead of DEX
      (control group). In experiment 1, the averaged b-wave amplitude of the TR-ERG
      decreased significantly (p < 0.01) at 3 hrs after RD in the control group, but it
      was almost stable and did not show significant decrease in the DEX group. In
      experiment 2, the averaged b-wave amplitude of the ERG decreased significantly (p
      < 0.05) at 2 hrs after the RD in the control, but showed no significant decrease
      even at 3 hrs after RD in the DEX group. These results indicate that DEX injected
      into the subretinal space and dropped onto the retina before producing RD may
      reduce ischemic damage in the detached retina.

PMID- 8533638
TI  - [A study on the rhodopsin gene in Japanese retinitis pigmentosa--screening of
      mutation by restriction endonucreases and frequencies of DNA polymorphisms].
AB  - We analyzed 11 sites of the rhodopsin gene using polymerase chain reaction (PCR)
      amplification and restriction endonucleases in 30 unrelated Japanese patients
      with autosomal dominant retinitis pigmentosa (ADRP). No point mutation was found
      in any patient. The frequencies of the single nucleotide (nt) substitution at nt
      269, nt 5145 and nt 5321 were examined in three groups, 38 unrelated patients
      with ADRP, 23 patients with autosomal recessive retinitis pigmentosa (ARRP), and
      67 normal controls. There was no significant difference in the frequencies of
      substitution among these three groups. The frequencies of A269G, G5145A, and
      C5321A were 52%, 36%, and 5%, respectively. These values were different from
      those of the American population. The polymorphisms, A269G and G5145A, are useful
      as DNA makers for linkage analysis.

PMID- 8533639
TI  - [Relationship between the nerve fiber layer defect and parafoveal visual field
      defects in glaucomatous eyes].
AB  - We evaluated the nerve fiber layer defect (NFLD) in glaucomatous eyes imaged by a
      scanning laser ophthalmoscope (SLO, Rodenstock Gm BH, Munich, Germany) and its
      relationship to parafoveal visual field defects. Twenty-three eyes of 20 patients
      with open angle glaucoma were studied. Only those eyes were used in which NFLD
      reaching the temporal raphe of the nerve fiber layer was observed by the SLO in
      either the superior or the inferior hemisphere. We defined three topographic
      parameters of the NFLD: 1. the angle (0, degree) generated by a line A passing
      through the foveal pit and the disc center, and a line through the disc center to
      the point of the NFLD at the disc edge and closest to line A, 2. the horizontal
      distance (D1, mm) along the temporal raphe between the foveal pit and the point
      of the NFLD nearest to the foveal pit, and 3. the vertical distance (D2, mm)
      between the foveal pit and the point of NFLD nearest to the foveal pit. We also
      defined the nearest defect location (in degrees from the fovea) as the stimulus
      point with sensitivity loss greater than 6 dB in the Humphrey visual field
      (program central 10-2). A highly significant correlation was observed between
      each of the three NFLD parameters and the nearest defect location (p < 0.001).
      The NFLD parameters we have newly defined here may be helpful for evaluating
      parafoveal visual functional damages in open angle glaucoma.

PMID- 8533640
TI  - [Rapid diagnosis of adenoviral conjunctivitis by enzyme-linked immunosorbent
      assay (Adenoclone)].
AB  - We evaluated an enzyme-linked immunosorbent assay test (Adenoclone) for the rapid
      diagnosis of adenovirus infection in 589 cases of acute follicular
      conjunctivitis. Of 255 cases of adenoviral conjunctivitis proven by positive
      virus isolation. Adenoclone was positive in 51.0% by visual determination and
      40.4% by spectrophotometry. Twenty-seven of 130 cases giving visually positive
      results were interpreted to be negative by spectrophotometry. In 334 adenovirus
      negative cases, Adenoclone was negative in 99.1% and 99.4 by visual and
      spectrophotometric determination, respectively. Adenoclone was less sensitive in
      cases of adenovirus 3, 4 or 37, infections than in those of adenovirus 8, and
      also showed lower sensitivity in cases presenting mild conjunctivitis. Adenoclone
      is a rapid and easy test with high specificity but low sensitivity, and thus the
      test seems to be helpful in diagnosing adenoviral conjunctivitis.

PMID- 8533641
TI  - [A comparison between scleral buckling procedure and vitrectomy for the
      management of uncomplicated retinal detachment caused by posterior retinal
      break].
AB  - We reviewed conventional scleral buckling and vitrectomy for uncomplicated
      rhegmatogenous retinal detachment due to posterior retina break. A comparison was
      made for a consecutive series of 21 cases undergoing scleral buckling procedure
      and 15 cases receiving vitrectomy as the initial surgery. As regards surgical
      complications, in the scleral buckling procedure there was inadvertent severance
      or compression of the vortex veins in 16 (77%) of the 21 cases and postoperative
      choroidal detachment in 9 (43%). In vitrectomy, there were no remarkable
      intraoperative complications, but it led to progressive nuclear cataract in 10
      (67%) of the 15 cases during the postoperative period. Both procedures produced
      successful retinal attachment with comparable visual recovery. The results
      indicate that vitrectomy is a useful procedure for cases of uncomplicated retinal
      detachment caused by deeply located retinal break.

PMID- 8533642
TI  - [Motion discrimination as as test for visual motion perception].
AB  - Recent neurophysiological studies have indicated that there are two parallel
      pathways in vision processing independently shape and motion. There are many
      methods for examining perception of color and shape, but none for examining
      visual motion perception. In this study, we devised a "motion discrimination task
      (MDT)" for evaluating motion perception, which was displayed on a computer
      monitor, and recorded normal responses to the MDT in 90 normal subjects.
      Responses to MDT were not affected by visual acuity, but were affected by dot
      speed of the MDT. There was little trial-to-trial or subject variability in the
      MDT. These findings indicate that our MDT is a good clinical test for evaluating
      motion perception in human subjects.

PMID- 8533643
TI  - [HLA and uveitis in leprosy].
AB  - In order to investigate the role of immunogenetic factors in the pathogenesis of
      uveitis in leprosy, human leukocyte antigens (HLA) were analyzed among leprotics
      with and without uveitis. The subjects were 85 Japanese leprosy patients, 44 with
      uveitis and 41 without uveitis. Controls were 138 healthy subjects. A modified
      two-stage complement dependent microcytotoxicity test was used for typing HLA-A, 
      B, -C, -DR and -DQ antigens. The occurrence of HLA-DR2 antigen was significantly
      increased in patients as a whole (69.4%), and in the patients with uveitis
      (79.5%) as compared with the control subjects (35.5%). The association with DR2
      was even stronger in the patients with uveitis (odds ratio = 7.1, Pc < 0.000005)
      than in the patients as a whole (odds ratio = 4.1, Pc < 0.0001). On the other
      hand, HLA-DR53 antigen was significantly decreased in the patients as a whole
      (43.5%) and in the patients with uveitis (36.4%) as compared with the control
      subjects (69.6%). No significant difference in the distribution of HLA antigens
      was observed in the patients without uveitis. Our results suggest that HLA-DR2
      contributes to the susceptibility to uveitis in Japanese leprosy patients.

PMID- 8533644
TI  - [Intraocular lens power calculation for short eye].
AB  - The accuracy of intraocular lens power calculation formulas for short eyes was
      examined. We examined 217 eyes with an axial length of shorter than 22.5 mm, with
      postoperative visual acuity of 0. 5 or more, and postoperative astigmatism of
      less than +/- 2D. Five formulas were tested for accuracy in prediction for
      postoperative refraction, the S-SRK, the SRK, the SRK II, the SRK/T, and the
      Binkhorst formulas. The best results were produced by the S-SRK formula which
      predicted 74% of the cases within +/- 1D error, if the axial length was shorter
      than 22 mm. The A-constant was also examined to study the effect of postoperative
      refraction. The A-constant takes into consideration the depth of the anterior
      chamber lens, so that the differences in depth would be influenced for short eyes
      rather than regular eyes in prediction. However, there was no significant
      difference among the different A-constant groups.

PMID- 8533645
TI  - [A case of encapsulated filtering bleb after trabeculectomy].
AB  - A case of encapsulated filtering bleb after trabeculectomy is reported. A 57-year
      old man with primary open angle glaucoma underwent a trabeculectomy one year ago.
      Six months after the operation the filtering bleb began to shrink and intraocular
      pressure (IOP) began to rise. It was suspected that the trabeculectomy site was
      obstructed by scarring, and so sclerostomy ab interno was performed in the site
      with a Nd: YAG laser. The IOP was higher elevated, however, and the bleb remained
      unchanged with severe conjunctival injection and aqueous inflammation. The next
      day trabeculectomy was performed in a new site and two weeks later a dome-shaped,
      prominent bleb was observed with an increase in the IOP. This was diagnosed as an
      encapsulated filtering bleb (Tenon's capsule cyst). Cystectomy of the bleb failed
      and it recurred, therefore, another trabeculectomy was added and the IOP was kept
      at a reasonable value. We believe that it is important to pay attention to an
      encapsulated filtering bleb as a complication of filtering surgery after laser
      therapy to the anterior chamber angle.

PMID- 8533646
TI  - [Medical treatment in corneal diseases].

PMID- 8533647
TI  - [Electron microscopic studies of retinal pigment epithelial cells incubated with
      L-dopa in 10% and 20% oxygen].
AB  - In order to make clear how the ultrastructure of the bovine second-passage
      retinal pigment epithelium (RPE) was affected by exposure to L-dopa and oxygen,
      we compared the toxic effects of melanotic and amelanotic RPE. The oxygen levels
      in the incubators and the L-dopa concentrations in the media were adjusted to 10%
      or 20% oxygen by adding nitrogen gas and 100 microM or 250 microM L-dopa,
      respectively. After 24 hours, melanotic and amelanotic RPE were fixed and
      embedded in epon. Ultrathin sections were examined by transmission electron
      microscopy. Rough endoplasmic reticula were found to be dilated and ribosomes
      were extinguished in both melanotic and amelanotic RPE. The damage by L-dopa in
      melanotic RPE was less than that in amelanotic RPE and less in 10% oxygen than in
      20% oxygen.

PMID- 8533648
TI  - [The effect of epidermal growth factor on keratocytes during healing of corneal
      penetrating incision].
AB  - We investigated the effect of epidermal growth factor (EGF) on keratocytes during
      corneal wound healing focusing on cell proliferation. A penetrating linear
      incision was made in the center of rabbit corneas. The corneas were then treated
      with eye drops of recombinant human EGF (10 micrograms/ml) or physiological
      saline (control) four times a day. After 1, 2, 3, and 7 days, the corneas were
      excised, labeled with 3H-thymidine (10 microCi/ml) at 37 degrees C for 4 hours
      and subjected to autoradiography. The results demonstrated increased number of
      keratocytes incorporating 3H-thymidine on the 1st, 2nd, 3rd and 7th days of
      healing and accelerated stromal wound healing in corneas treated with EGF
      compared with the controls. Thus, EGF stimulates of proliferation keratocyte and
      promotes corneal stromal wound healing.

PMID- 8533649
TI  - [Possible role of the AMPA/KA receptors in cultured Muller cells].
AB  - AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)/KA (kainate)
      receptors have been demonstrated in cultured Muller cells in a study on cytosolic
      free calcium ions ([Ca2+]i). The action of these receptors may be expressed under
      pathological rather than physiological conditions. 1. Critical concentration in
      response to AMPA was determined in retinal neurons and Muller cells. At 0.05mM
      AMPA, in all neurons and in only a limited number of Muller cells (20%) cytosolic
      calcium transients occurred. 2. The level of lactate dehydrogenase (LDH) and the
      change in [Ca2+]i following AMPA administration were measured before and after
      exposure to 0.5mM KA. Neither morphological change nor leakage of LDH could be
      detected after 24 hours. When AMPA was administered, the responsive cell number
      was higher for KA-exposed cells than for control cells. Muller cells may be
      concluded to resist neurotoxic agents and may possibly be involved in the
      survival mechanism of retinal neurons.

PMID- 8533650
TI  - [Ultrastructural changes in the lamina cribrosa in experimental monkey glaucoma].
AB  - We examined the ultrastructural changes in the lamina cribrosa in monkeys with
      experimental chronic glaucoma. In normal monkey eyes, the extracellular matrix
      consists of tightly packed collagen fibers, elastic fibers and less ground
      substance in the beams, and basement membranes associated with vascular cells and
      astrocytes in the lamina cribrosa. In the experimental glaucomatous eyes there
      was a marked destruction of collagenous bundles. The empty spaces were expanded
      and filled with fine fibrillar materials. There were normal by appearing parts
      and clearly destroyed parts mixed in the same region. Elastic fibers looked
      isolated from the collagenous bundles around them. Basement membranes were
      generally thick, multi-laminated, and bent. In addition, basement membrane-like
      materials, separated from the cells, were often seen in the laminar beams. The
      lamina cribrosa in experimental chronic glaucoma showed evidence of both
      destruction and healing or remodeling. These changes might have a influence to
      the worse for the tissue characterization of the lamina cribrosa, such as
      resistence to intraocular pressure changes. In conclusion, this may be a factor
      related with the progression of glaucomatous optic nerve damage.

PMID- 8533651
TI  - [Study on conservative treatment of retinoblastoma--effect of intravitreal
      injection of melphalan on the rabbit retina].
AB  - Effects of an intravitreal injection of melphalan on the electroretinogram and on
      the retinal structure were studied in albino rabbits to establish the non-toxic
      dose for its intravitreal use. The a-wave, the b-wave, the c-wave, the
      oscillatory potential and the retinal structure remained unchanged after 10
      micrograms injection, but moderately changed after 20-micrograms injection and
      greatly deteriorated after 90-micrograms injection. A 10-micrograms injection is
      equal to an intravitreal concentration of about 5.9 micrograms/ml, if evenly
      diffused in the rabbit vitreous. Considering that colony formation of in vitro
      retinoblastoma cells is completely suppressed by melphalan at 4 micrograms/ml
      concentration, an intravitreal application of melphalan could be used as a non
      surgical treatment for retinoblastoma.

PMID- 8533652
TI  - [Ultrastructural study of lens fiber cells by quick-freezing and deep-etching].
AB  - The ultrastructure of lens fiber cytoskeleton was studied by quick-freezing and
      deep-etching. Lenses of 5 Wistar male rats were divided into lens cortex and lens
      nucleus. Filamentous structures were clearly observed in the cortical fiber
      cells, which had diameters in 10 approximately 15 nm or about 5 nm. They showed a
      meshwork structure. On the other hand, the filamentous structures showed a
      linear, dense, and laminar pattern in the nuclear fiber cells. These
      ultrastructural changes of cytoskeletons may be related to the elongation and
      differentiation of lens fiber cells and may be important for maintaining
      transparency of the lens.

PMID- 8533653
TI  - [Effects of blowing or aspiration on ablation rate by excimer laser].
AB  - Accurate calibration of ablation rate by excimer laser prerequisite for precise
      photorefractive keratectomy (PRK). When a polymethylmethacrylate (PMMA) plate is
      ablated by excimer laser, debris is generated, which may affect homogeneity of
      the laser beam and energy density, and change the ablation rate. In order to
      clarify the effects of the debris on the ablation rate, we studied the changes in
      the ablation rate when the debris was removed by blowing or aspirating over the
      ablation area during PRK.PMMA plates were ablated using a scanning excimer laser
      system (EC-5000, NIDEK, Japan) in PRK mode under the following conditions: (1)
      with air blowing over the ablation area, (2) with aspiration of the debris, and
      (3) without treatment. The ablation rates were determined by measuring the
      refractive power of PMMA plates with a lens meter. The ablated surface was
      observed by scanning electron microscope (SEM). The ablation rate with blowing
      was the highest among the three conditions, that with aspiration was the second,
      and that without treatment was the lowest. The ablation rates with blowing showed
      no significant change when the ablation rates were changed. However, the ablation
      rates with aspiration or without treatment decreased as the pulse rate increased.
      The surface ablated during blowing was the smoothest in SEM photographs. We
      concluded that calibration of the ablation rate using PMMA plates must be done
      with appropriate air blowing.

PMID- 8533654
TI  - [Usefulness of the DNA-HLA class II typing in corneal transplantation].
AB  - DNA-HLA (human leukocyte antigen) typing was performed for ocular tissues in
      order to determine the usefulness of the method in corneal transplantation. Each
      type of ocular tissue was dissected from eye bank eyes (n = 3). DNA was
      extracted, and HLA-DRB1, DQB1, and DPB1 genes were amplified using PCR
      (polymerase chain reaction) method. DNA can be extracted and amplified from each
      ocular tissue except for the crystalline lens, but DNA from iris and choroid can
      be amplified only after diluting the samples 10 to 100 times. HLA class II
      antigens were successfully determined in these ocular tissues by the RFLP
      (restriction fragment length polymorphism) method. The method was applied to the
      corneal tissues of donor and recipient used for the corneal transplantation (n =
      7). HLA class II antigens can be determined in both the donor and recipient
      corneal samples, and the results of recipients' HLA typing were the same as those
      determined using the blood samples. These results indicate that the DNA-HLA
      typing can be used for ocular tissues. Since DNA-HLA typing is more accurate than
      the conventional serological typing, the method is promising for the study of HLA
      class II typing in corneal transplantation.

PMID- 8533655
TI  - [Ultrasound biomicroscopic imaging diagnosis of the anterior segment of the eye
      with high-frequency ultrasonic diagnostic equipment].
AB  - Micro-imaging displays of the anterior segment of the eye, such as of the
      anterior chamber angle, iris, ciliary body, ciliary zonule of Zinn, and anterior
      surface of the crystalline lens, were obtained in human eyes in vivo by means of
      a recently developed, high-frequency, high-resolution ultrasonic diagnostic unit
      (30 MHz). Much clearer displays than conventional ultrasonic imaging displays (5
      15 MHz) were obtained, showing improved resolution, and greater morphologic
      diagnostic information was provided. Displays considered useful for making
      measurements were also provided. The subjects were 20 normal volunteers (35
      eyes), 36 patients with glaucoma (58 eyes), 6 patients with uveal diseases (6
      eyes), and 28 patients with pseudophakia (32 eyes). The equipment used was a
      model UX-02 ultrasonic diagnostic unit (RION), and the transducer was the three
      element annular array type. The frequency was 30 MHz, the resolution was below 50
      microns, and tissue penetration was 6 mm. This method enabled close ultrasound
      biomicroscopic imaging observations of details of the anterior and posterior
      chambers of the eyes in vivo and was also useful for clinical diagnosis and
      elucidation of the cause of glaucoma of various types. It also for the first time
      enabled evaluation of the position of fixation of an intraocular lens loop in the
      pseudophakic eyes containing an intraocular lens.

PMID- 8533656
TI  - [Corneal sensitivity after cataract operation by corneal incision or scleral
      incision].
AB  - We studied postoperative corneal sensitivity after cataract operation by scleral
      incision (30 eyes) or corneal incision (29 eyes). Corneal sensitivity was
      evaluated at 5 points of the cornea with a Cochet & Bonnet esthesiometer at 3 and
      6 months after operation. Total value of corneal sensitivity decreased by 60 +/-
      5.0 mg/S (mean +/- deviation) 3 months after corneal incision and by 46 +/- 4.1
      mg/S after scleral incision. At 6 months after operation, the total value of
      corneal sensitivity was deceased by 14.0 +/- 2. 5 mg/S in corneal incision cases
      and by 7.9 +/- 2.0 mg/S in scleral incision cases. Corneal sensitivity after
      operation was decreased more by corneal incision than by scleral incision.

PMID- 8533657
TI  - [Dark rim around choroidal neovascularization in indocyanine green angiography].
AB  - Experimentally produced choroidal neovascularization (ChNV) surrounded by a dark
      rim in indocyanine green (ICG) angiography was studied histopathologically. Dark
      rims were seen in 28% of ChNVs which were detected with ICG angiography 2 weeks
      after photocoagulation. During the developing stage of ChNV, the dark rim around
      it was seen in the early phase of ICG angiography, but in the late phase, the
      dark rim became unclear because of extravascular dye leakage. During the
      regressive stage, the dark rim was seen in all phases of angiography. It was
      especially clear in the late phase. Histopathologically, at the site of the dark
      rim the retinal pigment epithelial cells proliferated to surround the ChNV in the
      subretinal space during both stages. These results show that proliferated retinal
      pigment epithelium surrounding ChNV blocks the fluorescence of the choroid, and
      causes the dark rim. The dark rim is helpful for diagnosis of ChNV.

PMID- 8533658
TI  - [Surgical effects of trabeculotomy after long-term topical antiglaucoma
      medications].
AB  - We retrospectively analyzed the effects of long-term topical antiglaucoma therapy
      on the results of trabeculotomy. We studied 83 eyes with 76 primary open angle
      glaucoma and 7 eyes with capsular glaucoma, each of which had undergone
      trabeculotomy alone and none of which had a history of laser trabeculoplasty or
      glaucoma surgery. The outcome of trabeculotomy was assessed after a minimum
      follow-up of 12 months. Using a life-table method, there was no significant
      difference in the outcome of trabeculotomy between groups divided by duration and
      type of preoperative topical therapy. There was not statistically significant
      difference in the intraocular pressure reduction between the groups of long or
      short duration of topical therapy. We concluded that the duration and type of
      topical antiglaucoma medications had no significant effect on the outcome of
      trabeculotomy.

PMID- 8533659
TI  - [Analysis of infiltrating lymphocytes in choroidal melanoma].
AB  - We performed immunohistochemistry on tumor infiltrating lymphocytes (TILs) in a
      78-year-old man with choroidal malignant melanoma. Cell suspensions of TILs from
      fresh specimens and peripheral blood lymphocytes (PBLs) were stained with anti
      CD3, anti-CD4, anti-CD8, anti-CD29, anti-CD45RA, and anti-human leukocyte antigen
      (HLA)-DR monoclonal antibodies and analyzed using three-color flow cytometry. In
      light microscopy, the number of infiltrating lymphocytes around the tumor was
      very small. Immunohistochemically, T lymphocytes were more numerous than B
      lymphocytes. Flow cytometric analysis showed that CD8+ cells were more numerous
      than CD4+ cells in CD3+ cells in TILs, and most of these cells also expressed HLA
      DR antigen. CD29+ (memory) cells were increased and CD45RA+ (naive) cells were
      decreased in CD4+ cells in TILs as compared with PBLs. We concluded that the
      increase in the percentage of activated memory T lymphocytes and the decrease of
      naive T lymphocytes may reflect a localized antigen-specific immunological
      response in choroidal malignant melanoma.

PMID- 8533660
TI  - [Primary trabeculectomy for open-angle glaucoma with mitomycin C].
AB  - We examined the results of postoperative intraocular pressure (IOP) control and
      complications of trabeculectomy with mitomycin C in open angle glaucoma patients
      who had not undergone any other ocular surgery. The subjects were 80 eyes of 70
      patients who underwent surgery with 0.04% mitomycin C as an adjunct for 3 minutes
      and were followed for 7-24 months (mean +/- standard deviation: 13 +/- 3.4). The
      preoperative IOP was 21-32 mmHg (mean +/- standard deviation: 24.6 +/- 4.3) in
      maximum tolerable medications. IOP control ratio, which was analysed with the
      Kaplan-Meier method at 24 months after surgery was 81.6% without any antiglaucoma
      medications, vs 92.0% with medications. These values were significantly higher (p
      < 0.05) than the results of trabeculectomy with 5-fluorouracil or without
      antimetabolic agents previously performed in our clinic. Shallow chamber in 18
      eyes (23%), choroidal detachment in 14 eyes (18%), hypotonus maculopathy in 7
      eyes (9%), and cataract progression in 5 eyes (7%) were recognised as
      complications. Although there are some complications to be conquered,
      trabeculectomy with mitomycin C seems to be effective in treating primary open
      angle glaucoma patients.

PMID- 8533661
TI  - Infantile hookworm disease in China. A review.
AB  - Hundreds of cases of infantile hookworm disease which shows bloody stools,
      melena, anorexia, listlessness and oedema, have been reported in China since the
      1960s. Hookworm eggs were detected in due course in the faeces of the reported
      cases. With the exception of a single worm identified as Necator americanus, all
      the adult worms expelled following chemotherapy or examined at autopsy were
      Ancylostoma duodenale. Many children showed clinical manifestations and eggs in
      their faeces on day 1-26 after birth, and more cases occurred within 3 months of
      birth. Evidently, these infections were mostly transmitted from the mothers by
      transplacental and/or transmammary routes.

PMID- 8533662
TI  - Seroprevalences of Toxoplasma, malaria, rubella, cytomegalovirus, HIV and
      treponemal infections among pregnant women in Cotonou, Republic of Benin.
AB  - Seroprevalences for toxoplasmosis, malaria, rubella, cytomegalovirus, HIV and
      treponemal infections were evaluated among 211 pregnant women residing in the
      Cotonou area, Republic of Benin. One hundred and thirteen women (53.6%) had
      toxoplasma antibodies, 185 (87.7%) malaria antibodies and 181 (85.8%) rubella
      antibodies. Among the 205 (97.2%) women with cytomegalovirus antibodies, 6
      presented recent or current infection. No HIV seropositivity was detected. Five
      (2.4%) of these women had a positive treponematosis serology corresponding to
      previous infection or reinfection. These results were compared with previous
      studies conducted in Africa. Routine serological screening should be recommended
      in young age and in pregnancy for rubella, only in pregnant women for HIV and
      toxoplasma infections, in order to control their possible consequences on women
      and newborns.

PMID- 8533663
TI  - Leishmania major MON-26 isolated from naturally infected Phlebotomus papatasi
      (Diptera: Psychodidae) in Isfahan Province, Iran.
AB  - In a survey of leishmania infections in phlebotomine sandflies in one of the most
      important focus of zoonotic cutaneous leishmaniasis (ZCL) at Borkhar, a rural
      district north of the city of Isfahan, central Iran, Phlebotomus (phlebotomus)
      papatasi Scopoli from gerbil and jird burrows were naturally infected with
      Leishmania major zymodeme MON-26. This is the first isolation and
      characterization of L. major from P. papatasi in Iran, from an area where human
      and rodent infections with L. major have been present for a very long time.

PMID- 8533664
TI  - The effect of Trypanosoma brucei brucei infection on rabbit plasma iron and zinc
      concentrations.
AB  - Changes in plasma iron and zinc concentration were studied in rabbits following a
      needle challenge with Trypanosoma brucei brucei clone ILTat 2.1. The infection
      resulted in a decrease of the concentration of both trace elements. Plasma iron
      concentrations decreased gradually and were decreased maximally to 52.3% of pre
      infection levels on day 18 post-inoculation. Plasma zinc concentrations, on the
      other hand, decreased more rapidly and were decreased maximally to 27.4% of pre
      infection levels on day 3 post-inoculation. The onset of these decreases
      coincided with the appearance of parasites in the peripheral blood. Furthermore,
      the magnitude of their decrease correlated closely with the level and duration of
      the parasitaemia. Other abnormal findings, namely, anaemia and periods of
      leucocytosis and leukopenia, were also observed. This study therefore
      demonstrates that depression in plasma iron and zinc concentrations is part of
      the acute phase response in rabbits infected with this clone of T. b. brucei.

PMID- 8533665
TI  - Putative Leishmania hybrids in the Eastern Andean valley of Huanuco, Peru.
AB  - During an outbreak of tegumentary leishmaniasis that developed in the 1990s in
      the Eastern Andean valley of Huanuco, Peru, the coexistence of Andean (uta) and
      sylvatic leishmaniases was suspected for ecological and geographical reasons, and
      sympatric sampling was carried out. Seven human isolates of Leishmania were
      characterized by multilocus enzyme electrophoresis, random amplification of
      polymorphic DNA and molecular karyotyping. The three methods identified 3
      isolates as L. braziliensis, and 4 isolates as putative hybrids with characters
      of L. braziliensis and L. peruviana. Data from Huanuco are compared to previous
      results from other areas endemic for uta. Biological and epidemiological
      implications are discussed.

PMID- 8533666
TI  - Cuticular hydrocarbon variation and progeny phenotypic similarity between
      laboratory breeds of allopatric populations of Argas (persicargas) persicus
      (oken) (acari: argasidae).
AB  - Cuticular hydrocarbons of laboratory breeds of four Argas (Persicargas) persicus
      (Oken) population samples were studied by gas chromatography. Cuticular
      hydrocarbon patterns were used to determine Nei's genetic distances among
      populations, and their average heterozygosity. Sixteen n-alkanes, 37
      monomethylalkanes and 26 dimethylalkanes were identified. Mostly quantitative
      differences were recorded between populations, rarely among males and females of
      the same population. A low genetic distance (0.0278-0.0781) together with a
      prominent degree of average heterozygosity (60.37-66.98%) were recorded in the
      population samples studied. When crossbreeds with adult specimens from the same
      or different geographical origins are performed, all larval progenies closely
      correlated within themselves and with their parents in hydrocarbon pattern. A
      slight matrocliny occurred in larvae coming from crosses of the same geographical
      source. From cross data it is postulated that hydrocarbons in A. persicus are
      inherited under a two dominant alleles hypothesis.

PMID- 8533667
TI  - Susceptibility of various mosquitoes of California to subperiodic Brugia malayi.
AB  - Laboratory experiments were conducted to determine the susceptibility of six
      species of mosquitoes, representing three genera, to subperiodic Brugia malayi.
      The black-eye, Liverpool strain of Aedes aegypti was the susceptible control.
      Mosquitoes were fed on microfilaremic jirds (Meriones unguiculatus). All
      mosquitoes, except wild caught Culex erythrothorax, were laboratory-reared and
      allowed to feed when 8 to 10 days old. Anopheles freeborni, Anopheles hermsi, and
      Culiseta inornata proved refractory. Both Anopheles species allowed invasion of
      flight muscle and development to the late first stage, after which larval growth
      ceased and melanization occurred. Culiseta inornata prevented any larval
      development. Culex tarsalis and Cx. erythrothorax proved highly susceptible to B.
      malayi infection. In all, 95.6% and 88.7% of the Cx. tarsalis harbored third
      stage larvae after infective feedings of 15.7 and 81.8 mf/microliters of blood,
      respectively, while only 11.5% were found susceptible when microfilaremia was low
      (1.1 mf/microliters). Culex erythrothorax demonstrated a susceptibility rate of
      82.3% with 17.0 mf/microliters. Both Culex species appear to be excellent
      experimental hosts for subperiodic B. malayi. This is the first conclusive
      evidence that mosquitoes of the genus Culex can naturally support the complete
      development of a stain of subperiodic B. malayi.

PMID- 8533668
TI  - Olfactory responses of host-seeking Anopheles gambiae s.s. Giles (Diptera:
      Culicidae).

PMID- 8533669
TI  - [Clinical and pathological studies of renal cell carcinoma with vein
      involvement].
AB  - To clarify the meaning of vein involvement, the clinical and pathological
      findings of the patients with renal cell carcinoma were examined. Out of 288
      patients treated for renal cell carcinoma-from 1961 to 1993 at Niigata Cancer
      Center Hospital, 238 patients were examined for vein involvement. Tumor stages
      were evaluated according to the general rules for clinical and pathological
      studies on renal cell carcinoma (2nd edition). In 154 patients, the stage was
      pV0, in 41 pV1a, in 23 pV1b and in 20 pV2. The 5-year survival rate was 72.2% in
      pV0, 60.1% in pV1a, 51.9% in pV1b and 30.0% in pV2. Histological findings as
      grade, tumor size, regional lymph node metastasis and distant metastasis were
      proportional to vein involvement. The difference in the survival rate and
      histological findings of primary tumor between pV1a and pV1b group was small but
      the difference between pV0 and pV1a was significant. Therefore, the histological
      and clinical studies of the cases with pV1a must be done carefully. The 5-year
      survival rate of the patients with pV2 and without distant metastasis was 50.0%.
      However, the prognosis of the patients with pV2 and with distant metastasis was
      poor. Therefore aggressive treatment was not recommended for these patients.

PMID- 8533670
TI  - [Long-term results of surgical treatment for renal pelvic and ureteral tumors].
AB  - Fifty eight cases of primary tumors in the renal pelvis and ureter were treated
      at Toranomon Hospital between 1983 and 1992. They consisted of 32 renal pelvic
      tumors, 21 ureteral tumors and 5 tumors at both sites. The age of the patients
      ranged from 30 to 84 years (mean 63.1). Surgery was performed in 56 cases.
      Radical nephroureterectomy with concomitant ipsilateral retroperitoneal lymph
      node dissection was performed in 38 cases. The other surgeries were radical
      nephroureterectomy without lymph node dissection in 9, nephrectomy in 4,
      resection of ureter and reanastomosis in 3, radical nephroureterectomy and
      cystectomy in 1 and partial nephrectomy in 1. Pathologically, 53 were
      transitional cell carcinoma (TCC), 2 were TCC plus squamous cell carcinoma and 1
      was TCC plus adenocarcinoma. Over-all survival rates (Kaplan-Meier) of 56
      surgical cases at 1, 3, 5 years were 92.2, 83.7 and 72.8%, respectively.
      Combination chemotherapy (M-VAC or CAP) was performed in 9 cases of metastatic
      disease and 1 case of bilateral disease. Of these 10 cases, one achieved complete
      remission, 2 no change and 7 had progressive disease. Adjuvant chemotherapy was
      performed in 21 cases after surgery. These 21 patients were of high risk in
      recurrence either Grade 3 or pT3. However, the 5-year survival rate was 77.3% in
      these patients. Thus we conclude that the adjuvant chemotherapy in high risk
      patients was effective in our cases.

PMID- 8533671
TI  - [Change in serum prostate specific antigen values in men who had no evidence of
      prostate cancer on initial biopsy].
AB  - To determine the need for repeat prostatic biopsy, we retrospectively evaluated
      19 men for longitudinal prostate specific antigen (PSA) for more than 20 weeks
      from initial biopsy. Their initial biopsy results revealed no evidence of
      prostatic cancer. They had no surgical therapy or hormone therapy after it. If
      they had a 50% increase in the PSA level from initial biopsy, we performed the
      second biopsy. Of the 5 men who had the second biopsy, 3 men had prostatic
      cancer.

PMID- 8533672
TI  - [Seminal plasma cytokines in nonbacterial prostatitis: changes following
      sparfloxacin treatment].
AB  - The detection of various cytokines; interleukin-1 beta (IL-1 beta), interleukin-6
      (IL-6) and tumor necrosis factor-alpha (TNF-alpha), was studied in patients with
      nonbacterial prostatitis (NBP), and the clinical efficacy of sparfloxacin was
      also reported. The seminal plasma of 11 normal men and 10 patients with NBP were
      examined for the cytokines. There was no IL-1 beta or IL-6 in the seminal plasma
      of normal men. TNF-alpha was detected in only one normal man. In the seminal
      plasma of the patients, IL-1 beta was detected in 2 out of 10, and IL-6 was also
      detected in 6. TNF-alpha was detected in 6 out of 10 patients with NBP. The rate
      of detection of IL-6 and TNF-alpha was significantly higher in the patients with
      NBP than in normal men. The average levels (range) of IL-1 beta, IL-6 and TNF
      alpha were 28 pg/ml (27-29), 110 pg/ml (25-476) and 25 pg/ml (6-113),
      respectively. After treatment with sparfloxacin at a dose of 100 mg to 200 mg per
      day, their symptoms disappeared. The number of leukocytes in the seminal plasma
      decreased to the normal level and these cytokines were not detected. The
      favorable clinical effect was achieved in 13 of the 17 patients (76%). These
      findings suggested that the cytokines have an important role in the pathogenesis
      of prostatitis and that the level of the cytokines are useful indicators in
      patients with prostatitis, particularly with NBP.

PMID- 8533673
TI  - Carboplatin-based combination chemotherapy for testicular cancer: relationship
      among administration dose of carboplatin, renal function and myelosuppression.
AB  - Carboplatin (CBDCA), a derivative of cis-diamminedichloroplatinum, has low renal
      and neural toxicity. The dose-limiting factor of this agent is myelosuppression.
      We experienced various degrees of myelosuppression, when the dose of CBDCA was
      determined by the body surface area (BSA) in CBDCA-based combination chemotherapy
      for testicular cancer. Calvert demonstrated that the dose of CBDCA administered
      should be adjusted by renal function, because CBDCA was excreted through the
      glomerulus. We report the relationship among 3 factors; the administration dose
      of CBDCA, renal function and the degree of myelosuppression. We treated 6
      patients with testicular cancer. A total of 22 courses of CBDCA-based combination
      chemotherapy was performed. The area under the curve (AUC) was calculated by the
      following formula, which was demonstrated in Calvert's study. CBDCA dose = AUC x
      (GFR + 25), GFR; glomerular filtration rate. The degree of myelosuppression was
      examined. All chemotherapy courses were divided into 2 and 3 groups according to
      BSA and AUC, respectively. WBC and Plt reduction rates and nadir counts were
      significantly correlated with AUC, and showed no significant relationship to the
      dose determined by BSA. This study revealed that the degree of myelosuppression
      was closely related with AUC, which reflects the renal function.

PMID- 8533674
TI  - Strain and sex differences in kidney carcinogenesis in rats treated with N-ethyl
      N-hydroxyethylnitrosamine and uracil.
AB  - We earlier demonstrated that simultaneous administration of EHEN and uracil for 3
      weeks resulted in enhancement of renal carcinogenesis in F344 female rats.
      Therefore, to establish a model of renal carcinogenesis in rats that can induce
      advanced renal carcinoma at a high incidence, differences in the susceptibility
      to N-ethyl-N-hydroxyethylnitrosamine (EHEN) and uracil of the kidneys in male and
      female rats of two strains were examined. Group 1 (male Wistar rats), group 2
      (female Wistar rats), group 3 (male F344 rats), and group 4 (female F344 rats)
      received a 3-week simultaneous administration of 0.05% EHEN in the drinking water
      and 3% uracil in the diet after one week's acclimation. In all the above four
      groups, the rats were thereafter given a basal diet and water without chemical
      addition for a 29-week period. Group 5 (male Wistar rats), group 6 (female Wistar
      rats), group 7 (male F344 rats) and group 8 (female F344 rats) received no
      chemicals for the entire 33 weeks. At the end of the experiment, renal
      adenocarcinomas were found in 85, 68, 14 and 0% of the rats in groups 1, 2, 3 and
      4, respectively. The incidence of adenomas and adenocarcinomas in Wistar rats
      were significantly greater than in F344 rats (p < 0.0001). These findings
      indicate strain and possibly sex differences in kidney carcinogenesis in rats
      treated with EHEN and uracil, and simultaneous administration of the two agents
      to male Wistar rats might have an advantage for models to induce advanced renal
      carcinoma at a high incidence.

PMID- 8533675
TI  - [Retroperitoneal myxoid leiomyoma: report of a case].
AB  - We report a case of retroperitoneal myxoid leiomyoma in a 36-year-old woman
      complaining of urinary retention. An ultrasonogram revealed a mass in the pelvic
      space, while CT and MRI demonstrated a retroperitoneal tumor. Open resection of
      the tumor was performed. The resected tumor weighed 600 g and measured 16 x 11 x
      9 cm. Histological examination disclosed a tumor mainly composed of smooth muscle
      with myxomatous change and only rare mitoses. The pathologic diagnosis was
      retroperitoneal myxoid leiomyoma. Twenty-seven cases of this type of lesion
      previously reported in the Japanese literature were reviewed.

PMID- 8533676
TI  - [Asymptomatic unilateral adrenal medullary hyperplasia with a cyst: case report].
AB  - A 45-year-old man was admitted with asymptomatic adrenal tumor. He had normal
      plasma and urinary catecholamine levels. The swelling of right gland was detected
      by CT scan and MRI. Selective venous samplings were performed and the level of
      catecholamine into the right adrenal vein were much higher than that into the
      left one. On July 15th, 1993, a right adrenalectomy was carried out and the right
      adrenal gland with a large cyst could be found. The ratio of cortical area to
      medullary area was about 4:1. Therefore, it was pathologically diagnosed as
      adrenal medullary hyperplasia with a cyst. There are relatively few reports of
      adrenal medullary hyperplasia. Before the operation, the patients were mostly
      diagnosed as pheochromocytoma by the results of laboratory studies and their
      symptoms. The condition of this disease is usually bilateral and often associated
      with type II multiple endocrine neoplasia (MEN II). We describe a case of
      asymptomatic unilateral adrenal medullary hyperplasia.

PMID- 8533677
TI  - [A case of spontaneous rupture of renal cell carcinoma].
AB  - There have been a few reports on the spontaneous rupture of renal cell carcinoma.
      A 67-year-old female patient complaining of vomiting and severe abdominal pain
      was referred to our hospital. Plain computerized tomography demonstrated large
      heterogenous mass in the right retroperitoneum. We suspected the hemorrhagic
      shock because of the rupture of the right kidney and therefore emergent
      laparotomy was performed. Simple nephrectomy for the right kidney was performed.
      A pathological report revealed renal cell carcinoma, granular cell subtype, grade
      1, pT3a. The patient has been followed for one year and five months after the
      operation, there has been no evidence of local recurrence or distant metastasis
      of cancer. Thirteen cases of spontaneous rupture of renal cell carcinoma in the
      Japanese literature are reviewed.

PMID- 8533678
TI  - [Benign hemorrhagic renal cyst diagnosed by endoscopic biopsy: a case report].
AB  - A case of benign renal hemorrhagic cyst in a 73-year-old man is reported.
      Ultrasonography, computed tomography and magnetic resonance imaging revealed a
      solid mass in the left renal cyst. Percutaneous puncture of left renal cyst was
      carried out followed by endoscopic biopsy of the intracystic masses. Specimens
      showed no malignancy. As we could not rule out malignancy, left partial
      nephrectomy was performed. The surgical specimen was free from malignancy by
      pathological examination. Thus endoscopic biopsy of intracystic tumor indicated
      the correct diagnosis.

PMID- 8533679
TI  - [Prostatic adenocarcinoma showing features of endometrioid and mucinous
      carcinomas: a case report].
AB  - A 77-year-old male was admitted for the examination of post renal acute renal
      failure. Blood examination revealed renal dysfunction and elevation of
      carcinoembryonic antigen (CEA). Computed tomography and retrograde pyelography
      showed bilateral hydronephrosis due to ureteral stenosis. He died of renal
      failure and autopsy was done. Histologic findings showed moderately
      differentiated adenocarcinoma of the prostate associated with endometrioid and
      mucinous carcinoma, and metastases of retroperitoneal lymph nodes and multiple
      bones. Immunohistochemically, endometrioid carcinoma was positive for prostatic
      acid phosphate (PAP) and prostatic specific antigen (PSA), and negative for CEA.
      Mucinous carcinoma was negative for PAP and PSA, and positive for CEA. Including
      our case, 29 cases of endometrioid and 32 of mucinous carcinoma of the prostate
      reported in the Japanese literature are reviewed.

PMID- 8533680
TI  - [Testicular cancer in father and son].
AB  - The first report of the familial testicular cancers in a father and his son in
      Japan was presented. The father had right testicular seminoma at 41 years of age
      and his son had right testicular embryonal cell carcinoma associated with
      teratoma elements at 17 years of age. To date only 30 pairs of testicular cancers
      occurring in father and son have been reported worldwide. Survey of the
      literature suggested that hereditary factors might be involved in the familial
      occurrence of testicular cancers although there was no definitive evidence.

PMID- 8533681
TI  - [A case of adult pure yolk sac tumor of the testis achieving pathological
      complete response by chemotherapy].
AB  - We report a case of pure yolk sac tumor of the left testis in a 22-year-old male.
      He consulted a physician with left back pain and induration of his left scrotal
      content in December, 1992. Intravenous pyelography (IVP) revealed left
      hydronephrosis. Computerized tomography (CT) revealed para-aortic lymph node
      swelling and lung metastases. Left high inguinal orchiectomy was performed.
      Histopathological diagnosis was pure yolk sac tumor. After two courses of "COMPE"
      chemotherapy consisting of cisplatin, vincristine, methotrexate, peplomycin and
      etoposide, two courses of "high dose "COMPE" chemotherapy and three courses of
      "high dose COME" chemotherapy without peplomycin, he achieved a partial response
      (the regression rate of the pulmonary metastases and the retroperitoneal lymph
      node metastasis were 100% and 96.0% on CT, respectively) and the residual masses
      in the retroperitoneum were removed. Necrosis and xanthogranulomatous fibrosis
      were found in the resected material. The patient showed no evidence of disease
      two years after chemotherapy.

PMID- 8533682
TI  - [A case of chronic scrotal hematocele].
AB  - A 60-year-old man visited our hospital because of a painless swelling of the left
      scrotal content which enlarged gradually for these five years. He had no history
      of trauma at the perineum. Tumor markers such as HCG, AFP and CEA were within
      normal limits. Left high orchiectomy was carried out after the admission under
      the diagnosis of suspicious testicular cancer. The resected mass, 16.5 x 12.5 x
      9.5 cm in diameter and 900 g in weight, was encapsulated within the tunica
      vaginalis by a fibrous membrane and contained about 300 ml of reddish black
      liquid. The normally-appearing left testis was located separately from the mass.
      Microscopic examination revealed depositions of cholesterine crista in the wall,
      which are characteristic for a chronic hematocele.

PMID- 8533683
TI  - [A case of abdominal desmoid causing urinary tract obstruction].
AB  - A 62-year-old male patient presented with a complaint of the lower abdominal
      distention. Ultrasonography demonstrated bilateral hydronephroses and a huge
      heterogeneous mass in the pelvic cavity. Excretory urogram showed left-non
      visualized kidney and right-hydronephrosis. CT showed a heterogenous mass,
      situating 25 cm in diameter, adjacent to the left side of the bladder. Tumor
      resection was carried out on May 17th of 1994. Histopathological diagnosis of the
      surgical specimen was abdominal desmoid with HE stain.

PMID- 8533684
TI  - [Clinical statistics of 67 cadaveric renal transplantation at the Department of
      Urology, Kinki University School of Medicine].
AB  - A statistic survey was made on the patients undergoing cadaveric renal
      transplantation between June, 1980 and December, 1993. The total number of
      patients was sixty-seven. The number of patients per year increased annually. The
      graft survival rate was 73.8% at 1 year and 63.1% at 5 years. Some transition was
      seen in immunosuppressive regimens using cyclosporin.

PMID- 8533685
TI  - [The evaluation of surgical management for metastatic lesions of renal cell
      carcinoma].
AB  - The clinical experience with 29 renal cell carcinoma patients who underwent
      resection of their metastatic lesions was reviewed. Fourteen patients had no
      metastatic lesions when nephrectomy was performed initially (initial M0 group)
      and 15 patients already had detected metastases at diagnosis of their renal
      tumors (initial M1 group). The final point of follow-up was May 31, 1994.
      Eighteen patients (M0 9, M1 9) were curatively resected and 11 (M0 5, M1 6)
      underwent non-curative resection. In the curatively resected group, 7 patients (3
      lung, 2 adrenal gland, 1 brain, 1 bone metastasis) were alive with no recurrence
      followed from 50 to 174 months. Eight died from tumor recurrences, 1 was alive
      with tumor recurrence and 2 died from other diseases. The 3-year and 5-year
      survival rates in the curatively resected group (16 patients, excluding 2 who
      died from other diseases) were 87.5% and 61.9%, respectively, according to the
      Kaplan-Meier method. On the other hand, the 3-year and 5-year survival rate in
      the non-curatively resected group were 36.4% and 27.3%, respectively. Between the
      curatively resected group and non-curatively resected group, a significant
      difference was shown concerning the survival rate (3 year: P = 0.0018, 5 year: P
      = 0.003, generalized Wilcoxon method). We concluded that curative resection was
      the most important prognostic factor in the treatment of metastatic lesions.

PMID- 8533686
TI  - [Clinical analysis of 62 patients with blunt renal trauma].
AB  - Sixty two patients with blunt renal trauma were treated and followed in our
      clinic between 1976 and 1993. Immediate operation was performed in one with major
      laceration, 3 with ruptures and one with pedicle injury, that is, nephrectomy in
      4 and partial nephrectomy in one. Expectant management with the purpose of
      preserving the injured kidney was performed in 33 contusions, 20 minor
      lacerations and 5 major lacerations, resulting in no complications. We confirm
      that expectant management of blunt renal trauma may be reliable if the condition
      of the patient is stable even in the case of rupture, and the treatment of
      associated injury is preferential.

PMID- 8533687
TI  - [Laparoscopic unroofing of a renal cyst].
AB  - Laparoscopic unroofing of a renal cyst was performed in 13 cases of simple cysts
      of 48 ml. to 678 ml. (mean: 217 ml.) preoperatively measured by ultrasonography
      from April, 1994 through April, 1995 at our Department of Urology. Under general
      anesthesia, the renal cyst wall was resected as close as possible to the renal
      parenchyma by the laparoscopic technique. The postoperative outcome was evaluated
      in 12 of 13 cases, except for the one case converted to laparotomy because of
      uncontrollable bleeding from the resected site of the renal parenchyma. Three
      months after the operation, complete disappearance of the renal cyst was noted by
      CT scanning in 10 of the 12 cases. In the remaining 2 cases, the renal cyst was
      still in existence despite the apparent reduction of the cyst volume. In one case
      in which a somewhat large cyst remained, sclerotherapy using minocycline was
      carried out. No serious complications during the operation were observed, but in
      one case with uncontrollable bleeding as mentioned above, the postoperative
      course was uneventful. These findings indicate that, the laparoscopic unroofing
      of a renal cyst is a safe and useful procedure for a relatively large renal
      simple cyst, therefore this approach seems to be acceptable, and before long it
      will be an ordinary urological operation.

PMID- 8533688
TI  - [Clinical outcome of radical prostatectomy and pelvic lymph node dissection].
AB  - Between September, 1987 and September, 1993, a total of 44 consecutive patients
      had undergone radical retropubic prostatectomy and pelvic lymphadenectomy for the
      treatment of prostate cancer. The patients were between 56 and 77 years (mean, 68
      years). Eleven patients had clinical state A2 disease, 21 had stage B disease,
      and 12 had stage C disease. Fourteen of the 44 patients (32%) had positive lymph
      node metastases. The 5-year survival rate for patients with pT1, pT2 and pT3 was
      100%, 71% and 87%, respectively. It was 77% in patients with positive node
      disease and 90% in patients with negative node disease. The 5-year disease-free
      survival rate for patients with pT1, pT2 and pT3 was 82%, and 78%, respectively.
      It was 54% in patients with positive node disease and 88% in patients with
      negative node disease. In 14 positive node patients, metastases were located in
      obturater nodes in 8 patients (57%), hypogastric nodes, in 6 patients (43%),
      external iliac nodes in 6 patients (43%), common iliac nodes in 4 patients (29%)
      and presacral nodes in 2 patients (14%). We confirmed that radical retropubic
      prostatectomy is effective treatment for locally confined prostate cancer and
      removal of obturater, hypogastric lymph nodes and the internal chain of external
      iliac lymph nodes is important in detecting metastases.

PMID- 8533689
TI  - [A case of renal capsular liposarcoma].
AB  - A 53-year-old woman was admitted to the Department of Internal Medicine at our
      hospital with the primary complaint of pyrexia. Abdominal echography and computed
      tomography (CT) detected a right renal tumor, and the patient was transferred to
      our department. Angiography revealed a hypovascular tumor. The main nutrient
      vessels supplying the tumor were the superior and inferior capsular arteries,
      which arose from the renal artery. A right renal capsular tumor was suspected
      from these findings, and radical nephrectomy was performed. Histopathological
      examination revealed a pleomorphic liposarcoma. Therefore, the patient was given
      50 Gy of radiation postoperatively. This is the 14th case of a primary
      liposarcoma of the renal capsule reported in Japan.

PMID- 8533690
TI  - [Two cases of squamous cell carcinoma of the ureter].
AB  - Herein, we report two cases of squamous cell carcinoma of the ureter. The first
      case was in a 56-year-old-male. Total cystectomy and ileal conduit were performed
      because of bladder tumor suspected to be accompanied by carcinoma in situ and
      atrophic urinary bladder induced by chronic cystitis in December, 1993.
      Pathological examination revealed transitional cell carcinoma (TCC) > squamous
      cell carcinoma (SCC), G2 > G1, INF beta, pT1, 1y1, v1. He complained of back pain
      under medical observation in December, 1994. Left hydronephrosis was found and
      antegrade pyelography showed leakage from the left pelvic ureteral junction.
      Urinary cytology revealed class V and suggested TCC. He received left
      nephroureterectomy, and pathohistological examination of resected specimen
      revealed SCC, INF gamma, pT3, pRo, pLx, pVx, pNo, pMo. CABO chemotherapy
      (cisplatin, methotrexate, bleomycin, vincristine) was performed postoperatively.
      The second case was in a 61-year-old female. She complained of macrohematuria in
      the course of observation of pyelonephritis. Drip infusion pyelography showed
      right hydronephrosis and retrograde ureterogram revealed stenosis of the right
      lower ureter. Urinary cytology revealed class V. Nephroureterectomy and bladder
      cuff were performed. The tumor was histologically diagnosed as SCC > TCC, INF
      beta, pT3, pRo, pLo, pVo, pNo, pMo. Postoperatively, CABO chemotherapy was
      performed. So far, no recurrence has been observed. Fifty five cases of squamous
      cell carcinoma of ureter were collected from the Japanese literatures including
      our cases.

PMID- 8533691
TI  - [A case of leiomyosarcoma of the diverticulum of urinary bladder].
AB  - A 77-year-old man was admitted to our hospital complaining of gross hematuria.
      Cystoscopy showed an approximately 4-cm non-papillary tumor in and out of the
      diverticulum of the left posterior wall. Total cystectomy was performed.
      Histopathological diagnosis was pleomorphic leiomyosarcoma. According to TNM
      classification of bladder cancer, the stage of this tumor was pT3bpN0M0. The
      patient had local recurrence two months after the operation, and died a month
      later. This is the second case of leiomyosarcoma of the diverticulum of urinary
      bladder reported in Japan.

PMID- 8533692
TI  - [A case of urethral diverticulum in a male paraplegic patient].
AB  - A case of acquired diverticulum of the male anterior urethra is reported. A 67
      year-old man with Pott paralysis caused by tuberculous spondylitis, visited our
      clinic due to recurrent urinary tract infection. He had used a condom penile
      sheath to collect urine. Voiding and retrograde cystourethrograms revealed
      anterior urethral diverticulum. Magnetic resonance imaging (MRI) clearly
      demonstrated diverticulum and corpus cavernosum penis, but corpus spongiosum
      penis was not defined. Urethroscopy showed diverticulum in the shape of partially
      dilated urethra with normal urethral mucosa. After diverticulectomy, self
      catheterization was endorsed. Histological study of removed diverticulum revealed
      squamous epithelium and fibrous connective tissue in the wall. The urethral
      diverticulum of this patient might have arisen from the elevated urethral
      pressure caused by the condom penile sheath.

PMID- 8533693
TI  - [A case report of prostate cancer with Paneth cell-like change].
AB  - We report one case of Paneth cell-like change of prostate cancer. An 81-year-old
      male reported to our hospital with the chief complaint of urinary retention. The
      serum concentration of prostate specific antigen, 168 ng/ml, was high, and
      digital examination was performed. Because we suspected prostate cancer, needle
      biopsy of the prostate was performed. Histological examination revealed
      moderately-poorly differentiated adenocarcinoma. Computed tomography revealed no
      invasion to the prostatic wall and no metastasis to the lymph node. 99mTc-HMDP
      revealed no bone metastasis. We chose intravenous hormonotherapy (fosfestrol 500
      mg/day, 20 days), but urinary retention did not improve. Therefore, we performed
      transurethral prostatectomy to improve the symptoms. Histological examination of
      the removed specimen revealed moderately differentiated adenocarcinoma with
      Paneth cell-like change. Immunochemical and histochemical stains were positive
      for Grimelius, serotonin and prostatic acid phosphatase and negative for periodic
      acid-Schiff reaction, lysozyme, neuron specific enolase, prostate specific
      antigen, alpha-1-antitrypsin and IgA.

PMID- 8533694
TI  - [Malacoplakia of the prostate: report of a case].
AB  - We report a case of prostatic malacoplakia clinically diagnosed as prostatic
      cancer. A 65-year-old man was seen with increased urinary frequency, and
      urinalysis disclosed moderate pyuria. After the administration of antibiotics for
      several days, the urine was sterile and the symptoms disappeared, but findings of
      digital examination of the prostate were compatible with prostatic cancer.
      Transperineal needle biopsy of the prostate was reported as poorly differentiated
      adenocarcinoma on the piece from the left lobe. Following further evaluation, the
      patient underwent radical prostatectomy under the preoperative diagnosis of stage
      B1 prostatic cancer. However, histological diagnosis of the surgical specimen was
      malacoplakia of the prostate.

PMID- 8533695
TI  - [Current practice and controversies in urinary diversion--the selection of the
      operation method of urinary diversion and postoperative care].
AB  - Since Kock et al. reported a low pressure continent reservoir using detubularized
      ileal segment as urinary diversion following cystectomy, continent urinary
      diversion including neobladder has been focused upon. On the other hand,
      ureterocutaneostomy, or ileal conduit as an incontinent urinary diversion is
      still commonly used, and especially the latter form is usually performed in many
      hospitals. These facts suggest that it is difficult to conclude that continent
      urinary diversion regarded as an excellent operation with good quality of life
      (QOL) is a generally acceptable method and that there are still some problems to
      decide the indication for urinary diversion. We discuss the problems about the
      postoperative complications and care of urinary diversion after cystectomy and
      our opinion about the selection of these operations.

PMID- 8533696
TI  - [Experience with incontinent urinary diversion--review of 31
      ureterocutaneostomies, 101 ileal conduits and 107 colonic conduits].
AB  - During the past 20 years, 31 ureterocutaneostomies (UC), 101 ileal conduits (IC)
      and 107 colonic conduits (CC) were performed. In the UC group, most of the
      patients were aged or had unresectable invasive pelvic malignancies. The
      operative mortality was 6.5% and acute pyelonephritis was noted frequently
      (48.3%). Stomal stenosis also developed significantly (63.5%). The operative
      mortalities in the IC group and CC group were 6.9% and 9.3%, respectively.
      Although the incidences of bowel obstruction, bowel fistula and renal calculi
      were higher in the IC group (18.8% vs 7.5% and 6.9% vs 0%, respectively). The
      serum creatinine level was lowest in the CC group (0.90 +/- 0.46 mg/dl) and
      highest in the UC group (1.36 +/- 0.75 mg/dl). Conduit ureteral reflux was
      frequent in the UC group (66.7%) but rare in the CC group (1.3%). We conclude
      that UC should be indicated in the selected patients with high risk, and IC and
      CC are indicated in patients who may have good prognosis but not indicated for
      continent reservoir or neobladder. We prefer CC in the younger group.

PMID- 8533697
TI  - [Current concept and problems of urinary diversion. 2. Selection of operation:
      reservoir].
AB  - The Kock continent urinary reservoir was constructed in 12 patients from 1988 to
      1990 followed by the Indiana continent urinary reservoir in 14 patients
      thereafter. There were no perioperative death in either group. The period of
      postoperative follow-up was 11 approximately 70 months, with a mean of 58.9
      months. Several modifications of the operative technique were made to the
      original Kock pouch, but stone formation was observed in 5 patients (42%),
      resulting from foreign materials permanently in contact with urine. In the
      Indiana pouch group with a mean postoperative follow-up period of 26.8 months
      (range 11 approximately 43 months), wound infection occurred in the initial 4
      patients and difficulty of catheterization in the other 4 patients. The serum
      electrolyte values were found to be within the normal limits during the follow-up
      period in both groups, but, mild acidosis occurred in 2 patients. Patients with
      urinary diversion demonstrated mild azotemia (P = 0.02) despite similar serum
      creatinine levels and an increase in urine pH (P = 0.006) postoperatively.
      Asymptomatic bacteriuria was demonstrated in 22 of the 26 (83%) patients with the
      reservoir, but only 5 patients had significant pyuria. Our clinical experience
      suggests that the Indiana pouch is a more reliable method than the Kock pouch to
      construct a continent urinary reservoir.

PMID- 8533698
TI  - [Indication of neobladder replacement in patients undergoing radical cystectomy
      for bladder cancer].
AB  - Neobladder replacement has become an important procedure in the patient
      undergoing radical cystectomy for invasive bladder cancer. It yields
      postoperatively excellent quality of life in these patients. The indications of
      the patients selection have not been established, since long-term clinical
      results have not been presented and some issues such as urethral recurrence of
      the original disease, growth of the cancer from the neobladder made of the
      gastrointestinal tract and influences arising from orthotopic micturition are
      still unclear. We reviewed the reports describing neobladder replacement in the
      patients undergoing cystectomy for the bladder cancer. At present the criteria of
      patients selection described by most authors can be summarized as follows, (1)
      male patients, (2) patients having an available gastrointestinal tract for
      reconstructing the neobladder, (3) patients having a good renal function and
      liver function and could tolerate for the surgery and (4) patients with no
      evidence of disease in their urethra and prostate (direct invasion of the
      disease). As to carcinoma in situ within the bladder, some authors included their
      indication and the others contraindication.

PMID- 8533699
TI  - [Problems of postoperative care in urinary diversion: ureterocutaneostomy].
AB  - One hundred and nine patients underwent tubeless ureterocutaneostomy as a method
      of urinary diversion at the Department of Urology, Wakayama Medical College
      during the 22 years from 1972 to 1994. The follow-up period ranged from 4 days to
      15 years, with a mean of 27.3 months. The primary disease was bladder cancer in
      68 patients, uterine cancer in 23 patients, other pelvic malignancies in 11
      patients and benign disease in 7 patients. We used 4 types of
      ureterocutaneostomy; transureteroureterocutaneostomy was done in 13 patients,
      bilateral ureterocutaneostomy through a single stoma in 30 patients, bilateral
      ureterocutaneostomy with two stomas in 4 and unilateral ureterocutaneostomy for
      one available kidney in 62 patients. The construction of stoma was done according
      to inverted U of Z-shaped skin flap method (30 cases), everted nipple stoma (37
      cases) and Toyoda's method (42 cases). We evaluated the stomal condition in 72
      patients who were followed more than 6 months postoperatively. Stomal stricture
      developed and necessitated periodic dilatation or intubation in 25 cases (34%). A
      better outcome was obtained in patients with dilatated ureter and everted nipple
      type stoma but no correlation could be found between the history of irradiation
      and stomal stricture. Long-term outcome of ureterocutaneostomy in 70 patients
      (129 renal units) was, compared to that of ileal conduit urinary diversion in 124
      patients (248 renal units). Postoperative urographic findings showed progressive
      hydronephrosis in 14 renal units (23%) in the ureterostomy group, while 22 renal
      units (9%) in the ileal conduit group. However, there was no case of
      deterioration of renal function which was evaluated by BUN and creatinine in
      spite of progression of hydronephrosis. The incidence of urinary complications
      such as pyelonephritis and renal calculus in the successful ureterocutaneostomy
      group was less than that in the ileal conduit group.

PMID- 8533700
TI  - [Complications and quality of life in patients with ileal conduit diversion].
AB  - A series of 180 patients treated with ileal conduit urinary diversion at Nara
      Medical University and its affiliated hospitals were reviewed. The patients ages
      at the time of operation ranged from 21 to 79 years old with an average of 60.9
      years old and the average postoperative follow-up period was 44.2 months. Early
      complications occurred in 60 patients (33.3%) and 9 (5.0%) of them resulted in
      post-operative deaths. Late complications were noticed in 54 (31.6%) of the 171
      patients. Frequent late complications included peristomal dermatitis (37.3%),
      ureteroileal stenosis (17.9%) and urolithiasis (11.9%), for the latter two of
      which endourological treatments seemed to be effective. To be emphasized is that
      more attentive care should be paid to the condition of the peristomal skin during
      follow-up.

PMID- 8533701
TI  - [Postoperative care of continent urinary reservoirs].
AB  - Continent urinary reservoirs like the Kock pouch, Indiana pouch or Mainz pouch
      are constructed from the detubularized intestine. These types of urinary
      diversion are good in regard to the quality of life, but meticulous postoperative
      care is required to avoid complications. Continent urinary reservoirs have common
      problems of mucous secretion and absorption of urinary constituents. Irrigation
      of the reservoir to remove the mucous debris is important to prevent stone
      formation and infections. The patient should be educated to perform the self
      catheterization properly and the danger of over-distention of the reservoir
      should be stressed. Periodic endoscopy of the reservoir is important to confirm
      whether a stone or a tumor is present or not. Measurement of electrolytes and
      vitamin B12 should be performed to correct abnormalities if present.

PMID- 8533702
TI  - [Postoperative care of neobladder using a detubularized intestinal segment].
AB  - Neobladder using a detubularized intestinal segment was constructed in 74
      cystectomized patients between October 1986 and July 1994. There were 65 males
      (87.8%) and 9 females (12.2%) with an average age of 63 years (range 36 to 77
      years). The mean follow-up period was 35 months (range 7 to 85). Problems of
      postoperative care assessed were continence, renal function, metabolic
      consequences, neoplasms and other complications. Moreover, the impact of these
      problems on the quality of life was evaluated by a self-administered
      questionnaire. Continence in the daytime was achieved in 70/74 (94.6%) patients.
      Nocturnal incontinence was noted in 15/74 (20.3%) patients. Serum BUN and
      creatinine levels were maintained within normal limits. Metabolic acidosis (base
      excess < -5.0 occurred in 7/74 (9.5%) patients, 4 patients of whom needed
      alkalizing agents. Colon adenomas in neobladder were found and resected in 3
      patients. The other postoperative complications were stone formation in
      neobladder in 4 (5.4%), urethral stricture in 7 (9.5%) and ureteral stenosis in 3
      (4.1%) patients respectively, which were satisfactorily corrected by
      endourological procedures. As to quality of life assessment, the majority was
      satisfied, whereas 11% of the patients reported emotional distress and
      limitations in the usual physical activities by nocturnal incontinence. Our
      finding suggest that nocturnal incontinence is the most important problem and we
      need longer follow-up to evaluate the problems of metabolic consequences and
      neoplasms of the urinary tract.

PMID- 8533703
TI  - [Postoperative complications of self-catheterizable continent urinary diversions
      (Kock, Indiana, and appendiceal Mainz pouch) and patient care].
AB  - A self-catheterizable continent urinary reservoir has become one of the major
      options for urinary diversion in patients with invasive bladder cancer or other
      pelvic malignancies. We performed the Kock pouch, the Indiana pouch and the
      appendiceal Mainz pouch in 124, 51 and 4 patients with the mean followup periods
      of 50, 33, and 10 months, respectively. In the Kock pouch, the efferent and
      afferent nipple valve malfunction was seen in 16.7 and 21.3 percent each,
      requiring repair surgery, such as fixation of the efferent nipple to the pouch
      wall, reconstruction of an isoperistaltic nipple valve in the former, and removal
      of the Dacron fabric collar or re-anastomosis of the ureter to the pouch using
      LeDuc technique in the latter. In the Indiana pouch, stomal stenosis, an
      hourglass-like pouch deformity, difficult catheterization occurred in 3, 2 and 2
      patients, respectively. Among the 4 patients with the appendiceal Mainz pouch,
      there were no major late postoperative complications except for mild stenosis of
      the conduit, handled with bougienage. As a whole, surgical revisions, related to
      urinary diversion, was done in 20.3, 10.6, 0 percent in the Kock, Indiana, Mainz
      pouch patients, respectively. Stone formation, mostly multiple and recurrent,
      occurred in 27.8, 6.4, 0 percent in the Kock, Indiana, Mainz pouch, respectively.
      Most of the stones were removed endoscopically via a stoma or by percutaneous
      approach. Acidosis was seen in 3 patients in both the Kock and Indiana pouch, and
      3 patients with the Kock pouch suffered from symptomatic choleithiasis. At the
      time of the latest observation, continence was achieved in 90.2, 93.0, and 100
      percent, whereas excretory urograms showed normal collecting systems in 64.5,
      90.4, and 100 percent in the Kock, Indiana, and Mainz pouch, respectively. In
      conclusion, the Kock pouch, performed by an original method using unabsorbable
      polyester fabric collars and metallic staples, has an intolerably high rate of
      late complications, and either the modified Indiana pouch with ileal patch or the
      appendiceal Mainz pouch using the umbilicus as a stoma is recommended for a self
      catheterization continent urinary diversion.

PMID- 8533704
TI  - [Clinical statistics on outpatients during a ten-year period (1983, 10-1993, 12)
      at Department of Urology, Fukui Medical School].
AB  - A clinical statistic survey was carried out on the patients and disease
      experienced at the outpatient clinic of our Department of Urology, between 1983
      and 1993. Although the number of newly diagnosed patients was rather constant,
      the total number of outpatients gradually increased every year, and the average
      and median age of newly diagnosed patients became higher. The major disease
      categories were infectious and neoplastic disorders.

PMID- 8533705
TI  - Update on state prescribing authority.

PMID- 8533707
TI  - Alaskan adventures in pharmacy.

PMID- 8533706
TI  - Prescribing authority: an examination of Ohio pharmacists' opinions.
AB  - This study was conducted to determine the opinions of Ohio pharmacists about
      possible implementation of prescribing authority for pharmacists in the state.
      Questionnaires designed to determine pharmacists' opinions were mailed to a
      random sample of Ohio Pharmacists Association members. The overall net response
      rate was 44%. A majority of respondents preferred dependent prescribing authority
      under physician supervision. Respondents favored charging a fee for prescribing,
      although they did not expect the fee to be large enough to increase income
      substantially. A majority agreed that pharmacists should pass a qualifying exam
      and receive formal training to prescribe medications. A large number of
      respondents agreed that prescribing authority will lead to greater use of generic
      drugs and lower health care costs. For prescribing authority to succeed, it is
      suggested that appropriate protocols be developed in consideration of state
      requirements.

PMID- 8533708
TI  - Treatment of pregnancy-related illnesses.

PMID- 8533709
TI  - Pharmacists are heroes, too.

PMID- 8533710
TI  - Secundum artem, or the sensory side of pharmacy.

PMID- 8533711
TI  - An introduction to patient care outcomes: linking science with practice.

PMID- 8533712
TI  - The need to disseminate outcomes research.

PMID- 8533713
TI  - Demystifying outcomes for the pharmacist.

PMID- 8533714
TI  - Advanced counseling techniques: integrating assessment and intervention.

PMID- 8533715
TI  - Total quality management in hospital pharmacy.

PMID- 8533716
TI  - Attention-deficit hyperactivity disorder: the pharmacist's role.
AB  - Included in the variety of options for treating ADHD are several classes of
      pharmacologic agents with various side effects and monitoring parameters. The
      pharmacist must understand the issues involved with the use of the agents in each
      class. The pharmacist is often the most accessible health care professional and
      can take advantage of this fact to counsel and support both patients and family
      members. Table 5 offers counseling tips and additional information for the
      pharmacist. Of the medications discussed here, the stimulants are recognized as
      the most effective for treating ADHD, with the amphetamines and methylphenidate
      providing equal benefit. In some instances, pemoline has also been shown to be as
      effective as the other stimulants. Second-line agents are the TCAs, of which
      imipramine is the most commonly prescribed. However, the other TCAs are probably
      just as effective; some may have a less burdensome profile of side effects and
      may result in better compliance. Next in line is bupropion or clonidine, both of
      which show promise for ADHD treatment. Nevertheless, these agents need to be
      tested in more rigorous trials. Agents of last resort include the MAOIs, of which
      tranylcypromine has been the most studied. The ideal agent for treating ADHD
      would have an immediate onset, provide benefit throughout the day, have few or no
      side effects, lack the potential for abuse, be effective for most patients, and
      be relatively inexpensive. This ideal agent has yet to be discovered. Clinicians
      and researchers are still looking for a medication to come as close to the ideal
      therapy as possible. Therefore, it is not uncommon for a pharmacist to see a
      patient with ADHD try several different medications. In addition, children in
      whom ADHD is refractory to currently available options or who cannot tolerate
      these options may also be given other psychotropic medications not mentioned in
      this review.

PMID- 8533717
TI  - The role of the pharmacist in improving asthma care. National Asthma Education
      and Prevention Program.
AB  - Our current understanding of the pathophysiology of asthma and the availability
      of potent, effective therapies mean that asthma can be well controlled. However,
      to achieve this goal, optimal therapy must be prescribed and the patient must be
      taught how and when to use it. Pharmacists, as part of the health care team, help
      improve the pharmacologic management of asthma by teaching patients about their
      medications, how to use them, and the importance of using them as prescribed.
      Alerting physicians to suspected problems, such as underusing anti-inflammatory
      therapy or overusing inhaled bronchodilators, will provide an opportunity for the
      physician to consider changes in a patient's management plan when appropriate.
      Acting in these educational and information-sharing roles, pharmacists contribute
      to improving the control of asthma and enabling patients to live full, active,
      and productive lives.

PMID- 8533718
TI  - Asthma management can save lives.

PMID- 8533719
TI  - APhA sample protocol for chronic management of asthma. American Pharmaceutical
      Association Respiratory Disease Panelists and Reviewers.

PMID- 8533720
TI  - Pharmaceutical (who) care(s)?

PMID- 8533722
TI  - FDA considers OTC drug labeling reform.

PMID- 8533721
TI  - Understanding infertility treatment plans.

PMID- 8533723
TI  - Consultant pharmacy as a career or practice-building option.

PMID- 8533724
TI  - Update on biotech information sources.

PMID- 8533725
TI  - 1994 biotechnology drug approvals.

PMID- 8533726
TI  - New drugs of 1994.

PMID- 8533727
TI  - Helping pharmacists provide disease-based pharmaceutical care.

PMID- 8533728
TI  - Spotlighting working conditions, payment systems.

PMID- 8533729
TI  - Cyclosporine dosing for RA.

PMID- 8533730
TI  - Treating thyroid disorders.

PMID- 8533731
TI  - Drug-NSAID interactions.

PMID- 8533732
TI  - Compensation for cognitive services in the community pharmacy.

PMID- 8533733
TI  - Monitoring of Dinitrotoluene and its metabolites in urine by spectrophotometry of
      their coupled aryldiazonium salts.
AB  - A rapid, accurate method was developed for monitoring employee absorption of
      dinitrotoluene (DNT). The method reduces DNT and its metabolites in urine to
      primary arylamines, diazotizes them with nitrous acid, then couples the diazo
      compounds with N-(1-Naphthyl)ethylenediamine, producing a colored complex.
      Spectrophotometric analysis of the colored complexes at 550 nm provides a measure
      of DNT absorption. The chemistry prevents interferences from all but primary
      arylamines and compounds reduced to primary arylamines. A six-month monitoring
      program of employees at a DNT manufacturing facility was conducted. Control
      samples from individuals not exposed to DNT were used to define an exposure
      indication level. The exposure indication level was used to correlate DNT
      exposure with job description or individual activity and was defined as apparent
      DNT and metabolite concentrations greater than 38 micrograms/ml. Group exposure
      also was indicated and associated with plant activity. Job description were
      ranked according to a rational evaluation of exposure potential and correlated
      well with monitoring data.

PMID- 8533734
TI  - Evaluation of proposed methods to update human testing of self-contained
      breathing apparatus.
AB  - The current Man Test protocols used by the National Institute for Occupational
      Safety and Health for the certification testing of self-contained breathing
      apparatus (SCBA) do not provide continuous real-time information on the
      performance of these devices during actual use. In addition, current protocols do
      not test human subjects at the same absolute work rates but at rates that vary
      according to the subjects' body weights. This study was conducted to evaluate
      revised "Use Test" protocols proposed by the U.S. Bureau of Mines, which are
      normalized to subjects' body weights. No differences in duration were observed
      among the three body weight categories for the multiple work rate. Use Test 2. It
      was concluded that the proposed Use Test protocols could form the basis for
      eventual recommendations to revise the current Man Tests for SCBA performance
      evaluation.

PMID- 8533735
TI  - Stage hypnosis and public lecture effects on attitudes and beliefs regarding
      hypnosis.
AB  - Stage hypnosis shows, designed to entertain and amaze, and public lectures,
      designed to explain and educate, provide dramatically different introductions to
      hypnosis. This study examined how audience members' attitudes and beliefs
      regarding hypnosis are affected by these two different experiences. Two hundred
      and five college students completed pretest measures before either watching a
      stage hypnosis show, or attending a lecture on hypnosis, or participating in a
      control group. Subjects completed posttest measures between one to three weeks
      later. Both the stage hypnosis show and the lecture increased attendees'
      motivation to use hypnosis in treatment and decreased their belief that
      hypnotizability reflects lower intelligence. Moreover, the lecture also increased
      beliefs that hypnotizability reflects creativity and inner strength. Finally,
      while the lecture reduced the belief that a hypnotized person is robotlike and
      automatically acts on all suggestions, the stage hypnosis show increased this
      attitude among its audience members.

PMID- 8533736
TI  - Hypnosis in the treatment of functional infertility.
AB  - The literature was reviewed and found to contain sparse information regarding the
      applicability of clinical hypnosis in the treatment of functional infertility.
      Two cases were then described in which hypnosis based on imagery and a relaxation
      strategy was successful in facilitating pregnancy in both instances. The
      treatment was considered to have resulted in beneficial modification of attitude,
      optimism, and mind-body interaction.

PMID- 8533737
TI  - Hypnosis with signing deaf and hearing subjects.
AB  - Historically hypnosis with deaf people has been an underutilized intervention as
      the deaf were assumed not to be responsive to hypnotic suggestion. Recent
      research has begun to challenge these assumptions. Matthews and Isenberg (in
      press) compared the hypnotic responsiveness of deaf and hearing subjects on the
      Stanford Hypnotic Susceptibility Scale, form C (SHSS:C) all of whom received the
      hypnotic suggestions via sign language. Those results supported the notion that
      deaf subjects are capable of responding to hypnotic suggestion and may be as
      hypnotically responsive as hearing subjects. The purpose of the present article
      is to examine the similarities and differences of responses between deaf and
      hearing subjects to the individual items of the SHSS:C and compare those
      responses to the SHSS:C norms.

PMID- 8533738
TI  - Expectations and sequelae to hypnosis: initial findings.
AB  - As part of the introduction to an experiment using the Harvard Group Scale,
      subjects were given one of three brief instructions before being hypnotized: (1)
      no mention of negative or positive aftereffects, (2) vague warning of negative
      aftereffects, i.e., "some mildly unpleasant experiences", plus, "most persons
      report their experiences to be pleasurable and interesting", (3) specific warning
      of negative aftereffects, i.e., "approximately one half subjects have reported
      mild, short-term aftereffects such as headache", etc. (no positive information).
      The "specifically warned" Ss showed more negative aftereffects than both of the
      other groups, and the "no mention" Ss showed more than the "vaguely warned" Ss.
      The positive suggestions in the "vaguely warned" Ss instructions may have
      confounded the expectation for negative effects. A follow up study used
      instructions varying only in the degree of expectations for negative aftereffects
      (no mention of positive aftereffects). The results did not show group differences
      in negative aftereffects as predicted, however, correlational results suggested
      some interesting interactions among subject variables and the type of prehypnotic
      instructions administered.

PMID- 8533739
TI  - The use of a future time frame in psychotherapy with and without hypnosis.
AB  - Developments from various theorists and practitioners suggest an increasing
      interest in the use of future time frames in hypnosis and psychotherapy. We will
      present the development of a position focusing on the use of the future time
      frame without the necessary use of formal hypnosis. This position supposes an
      active, as opposed to a passive client role in the clinical interaction, and the
      techniques are applicable to a broader range of client population than other
      future oriented techniques. Thereafter, the use of this future time frame
      position is illustrated with case material, and potential interpretations of the
      case material are suggested.

PMID- 8533740
TI  - Hispanic origin and neural tube defects in Houston/Harris County, Texas. I.
      Descriptive epidemiology.
AB  - High prevalences of anencephaly and neural tube defects (NTDs) have recently been
      recorded for several Texas counties bordering Mexico. In addition, a few
      investigators have reported Hispanics to be at elevated risk for NTDs
      (anencephaly and spina bifida). Factors contributing to this risk have not been
      established. The authors conducted a study of NTDs in Harris County, Texas, to
      determine the prevalence of each defect. Prevalence was established by
      identifying cases among resident live births and fetal deaths (stillbirths at >
      or = 20 weeks) occurring from April 1, 1989, through December 31, 1991. Using
      multiple case ascertainment methods, 59 cases of anencephaly and 32 cases of
      spina bifida were detected, resulting in prevalences of 3.8 (95% confidence
      interval 2.9-4.9) and 2.0 (95% confidence interval 1.4-2.8) per 10,000 live
      births, respectively. The ratio of anencephaly prevalence to spina bifida
      prevalence was 2:1 in 1989, 1:1 in 1990, and 3:1 in 1991, with a significant
      difference in 1991. The female:male prevalence ratio was 1.0 for spina bifida and
      2.2 for anencephaly, and was higher still for anencephaly among non-Hispanics
      (prevalence ratio = 5.6). For each defect, Hispanics experienced a prevalence
      approximately three times that of non-Hispanics. This ethnic difference was
      greater for males with anencephaly and for females with spina bifida. For
      anencephaly, the Hispanic:white/Anglo prevalence ratio (4.2) and the African
      American:white/Anglo prevalence ratio (1.9) were greatly elevated and the
      Hispanic:African-American prevalence ratio (2.2) was similar, relative to
      comparable studies from the past two decades. The prevalence of anencephaly
      recorded for public hospitals (7.0 per 10,000) was three times greater than that
      for private hospitals (2.4 per 10,000). Spina bifida figures were similar for
      public (prevalence = 2.2 per 10,000) and private (prevalence = 2.0 per 10,000)
      hospitals. A significantly higher prevalence of both defects was documented among
      Hispanics in Harris County. The higher anencephaly rates among Hispanics, African
      Americans, and those using public hospitals in an era of NTD screening, prenatal
      diagnosis, and elective pregnancy termination suggest that socioeconomic and
      perhaps cultural/religious factors might influence the recorded birth prevalence
      of this defect in particular groups.

PMID- 8533741
TI  - Re: "Diet and nuclear lens opacities".

PMID- 8533742
TI  - Re: "The spectrum of medical conditions and symptoms before acquired
      immunodeficiency syndrome in homosexual and bisexual men infected with the human
      immunodeficiency virus".

PMID- 8533743
TI  - Hispanic origin and neural tube defects in Houston/Harris County, Texas. II. Risk
      factors.
AB  - Several investigators have reported Hispanics to be at elevated risk for neural
      tube defects (anencephaly and spina bifida). Factors contributing to this risk
      have not been established. The authors conducted a case-control study of neural
      tube defects (NTDs) among births occurring in Harris County, Texas, from April 1,
      1989, through December 31, 1991. Through the use of multiple ascertainment
      methods, 59 cases of anencephaly and 32 cases of spina bifida were detected.
      Controls (n = 451) were sampled for the same time period from Harris County vital
      records. Regardless of how Hispanic ethnicity was classified, having a Hispanic
      parent was a risk factor for both anencepahly and spina bifida. The primary
      etiologic question was whether increased NTD risk in Hispanics is explained by
      maternal diabetes or by other factors (e.g., maternal birthplace, prenatal care,
      reproductive history, age, socioeconomic status). Mexico-born Hispanics were no
      more likely than Texas-born Hispanics to deliver a fetus or infant with an NTD.
      Having a Hispanic mother was a risk factor for anencephaly among infants born to
      women with early prenatal care (odds ratio (OR) = 4.54, 95% confidence interval
      (CI) 2.21-9.40) but not for those born to latecomers. Earlier prenatal care
      seemed "protective" for non-Hispanics (OR = 0.18, 95% CI 0.06-0.65) but not for
      Hispanics. After simultaneous adjustment for eight variables in multivariate
      analysis, having a Hispanic (versus non-Hispanic) mother remained a strong risk
      factor for both anencephaly (OR = 2.58, 95% CI 1.19-5.61) and spina bifida (OR =
      3.71, 95% CI 1.48-9.31). Any previous pregnancy termination/fetal loss was also
      associated with anencephaly in a final logistic regression model (OR = 2.48, 95%
      CI 1.20-5.10), and having a teenage mother (aged < 20 years) approached
      significance (OR = 2.21, 95% CI 0.92-5.31). "Hispanic mother" was the only study
      variable significantly associated with spina bifida in multivariate analysis.
      Results for diabetes suggested no association with anencephaly (OR = 1.24, 95% CI
      0.25-6.17). An increased risk of NTDs among Hispanics remained after controlling
      for other factors. For anencephaly, this risk might be partially explained by
      economic and cultural differences between Hispanics and non-Hispanics, and the
      effect of these factors on rates of prenatal diagnosis and elective pregnancy
      termination.

PMID- 8533744
TI  - Case-control study of oral contraceptive use and risk of breast cancer.
AB  - The relation of oral contraceptive use to the risk of breast cancer in white
      women aged 25-59 years was assessed with data collected during 1977-1992 in a
      case-control surveillance system in hospitals in Boston, New York, and
      Philadelphia. A total of 3,540 cases with breast cancer were compared with 4,488
      controls with nonmalignant nongynecologic conditions unrelated to oral
      contraceptive use. Relative risk estimates were obtained by unconditional
      logistic regression with control for major risk factors. For at least 1 year of
      use relative to less than 1 year, the multivariate relative risk estimate was 1.7
      (95% confidence interval (CI) 1.3-2.3) in women aged 25-34 years, 0.9 (95% CI 0.7
      1.0) in women aged 35-44 years, and 1.2 (95% CI 1.0-1.4) in women aged 45-59
      years (p < 0.01 for the difference across age). Among women aged 25-34 years, the
      relative risk estimates were greatest for use of long duration, but the trend was
      not statistically significant (p = 0.17); in addition, the duration of use was
      correlated with the recency of use, and it was not possible to distinguish their
      effects. Among women aged 35-44 years, the relative risk estimate decreased with
      increasing duration of use (p = 0.01). Among women aged 45-59 years, some
      relative risk estimates were increased, but there was no consistent pattern. The
      results add to the evidence of an association between oral contraceptive use and
      an increased risk of breast cancer at young ages.

PMID- 8533745
TI  - Association of bone mineral density and sex hormone levels with osteoarthritis of
      the hand and knee in premenopausal women.
AB  - Mechanical stress on the cartilage and metabolic and/or hormonal influences have
      been suggested as possible etiologic factors for osteoarthritis. This paper
      reports findings from data collected in 1992 that were used to examine
      associations between osteoarthritis and risk factors in 573 Caucasian women aged
      24-45 years from the Michigan Bone Health Study. Radiographs of the dominant hand
      and both knees were evaluated using the Kellgren and Lawrence grading scale. The
      prevalence of osteoarthritis (grade 2 or higher) in this population was 2.8% for
      hands and 3.6% for knees. Using polytomous multiple logistic regression, the
      authors found older age, increasing bone mineral density, and decreasing
      testosterone levels to be significantly associated with increasing hand scores.
      Older age and hand injury were significantly associated with grades of 2 or
      higher. Increasing osteoarthritis knee scores were associated with older age,
      increasing bone density, increasing body mass index, and current use of hormone
      replacement therapy. A knee grade of 2 or higher was associated with increasing
      estradiol levels, knee injury, and higher blood pressure. This study indicates
      that age, bone density, and injury are risk factors common to the development of
      hand and knee osteoarthritis in this non-elderly female population.

PMID- 8533746
TI  - Spouse correlations in cardiovascular risk factors and the effect of marriage
      duration.
AB  - Spouse correlations in cardiovascular risk factors were investigated using data
      on 2,836 spouse pairs collected in the Busselton Population Health Surveys over
      the period 1966-1981. The risk factors considered were systolic blood pressure,
      diastolic blood pressure, body mass index, triceps fatfold, cholesterol, and
      forced expiratory volume (1 second). Statistically significant positive
      correlations (p < 0.01) were found for all (age-adjusted) variables. There was a
      statistically significant decreasing trend in the correlations for systolic blood
      pressure with marriage duration (trend p < 0.01). Although no other variables
      showed statistically significant trends, the correlations for diastolic blood
      pressure (p = 0.29), body mass index (p = 0.14), and forced expiratory volume (p
      = 0.16) also decreased with marriage duration, and correlations for cholesterol
      (p = 0.61) and triceps fatfold (p = 0.99) increased with marriage duration. These
      results suggest that there is spousal concordance in cardiovascular risk factors.
      The lack of consistent increasing trends in the correlations with marriage
      duration suggests that assortative mating may be a more likely explanation than
      the sharing of a common environment.

PMID- 8533747
TI  - Physical activity levels and changes in relation to longevity. A prospective
      study of Swedish women.
AB  - In 1968-1969, a population-based sample of Swedish women aged 38-60 years was
      recruited for a health survey, and 20-year survival was later ascertained from
      national registries. Occupational and leisure-time physical activity data from
      the baseline and 6-year follow-up examinations were evaluated in relation to all
      cause mortality among 1,405 women who were initially free of major diseases. In
      comparison with being inactive, the mortality relative risk associated with being
      somewhat active was 0.28 (95% confidence interval 0.17-0.46) for occupational
      activity and 0.56 (95% confidence interval 0.39-0.82) for leisure-time activity.
      Being in the most active occupational or leisure activity category further
      decreased mortality risk to a minor extent. A within-subject decrease in leisure
      activity over 6 years was also a significant risk factor for all-cause mortality
      (relative risk = 2.07, relative to no change), although there was no evidence of
      a benefit from increasing physical activity levels. Since exclusion of early
      endpoints did not affect the associations in any significant way, underlying
      illness is unlikely to have played a major role in these analyses. It is
      concluded that decreases in physical activity as well as low initial levels are
      strong risk factors for mortality in women, and that their predictive value
      persists for many years.

PMID- 8533748
TI  - Type A behavior pattern and change in blood pressure from childhood to
      adolescence. The Minneapolis Children's Blood Pressure Study.
AB  - The association of the Type A behavior pattern with change in blood pressure was
      examined in a multiethnic sample of schoolchildren. Blood pressure was assessed
      in 1978 (mean age = 8 years) and approximately biannually thereafter through 1987
      1990, when a post-high school screening was completed. The Matthews Youth Test
      for Health (MYTH) was completed by the teachers of a sample of participants in
      1982 (n = 502). The Jenkins Activity Survey (JAS) was completed by all
      adolescents who participated in the post-high school screening (n = 816). Males
      were more likely to be classified as Type A than were females by the JAS and the
      MYTH. Type A status was not associated cross-sectionally with elevated blood
      pressure. JAS-assessed Type B males had significantly higher mean post-high
      school fourth- and fifth-phase diastolic blood pressures than did Type A males
      (70.2 mmHg vs. 68.2 mmHg, p < 0.05; 68.1 mmHg vs. 65.2 mmHg, p < 0.01). JAS
      assessed Type A/B status was not associated with 10-year change in blood
      pressure. MYTH-determined Type B females tended to have higher diastolic blood
      pressures than MYTH-determined Type A females throughout the 10-year study
      period. Results from this study did not confirm the hypothesis that Type A
      participants would have significantly higher blood pressures than Type B
      participants at the time of Type A assessment; nor did they confirm the
      hypothesis that Type A participants would exhibit greater increases in blood
      pressure than Type B participants over a 10-year period.

PMID- 8533749
TI  - Risk factors for constant, severe trachoma among preschool children in Kongwa,
      Tanzania.
AB  - Trachoma, an ocular infection caused by Chlamydia trachomatis, is the second
      leading cause of blindness worldwide. The blinding sequelae, which occur in
      middle age, are felt to be the result of numerous or lengthy episodes of severe
      inflammatory trachoma in childhood. Risk factors for constant, severe trachoma
      were identified in a group of children enrolled in a longitudinal study in
      Kongwa, Tanzania, where villages were randomized in a clinical trial of mass
      treatment and a behavior modification campaign. In 1989, each of 1,417 randomly
      selected children had photographs taken of an upper eyelid for determination of
      their trachoma status. The photographs were graded by a reader who was masked as
      to the village and date of each photograph. Risk factor data on the family's
      socioeconomic status, distance to water, and hygiene practices were obtained at
      baseline. Follow-up examinations occurred 2, 6, and 12 months from baseline. Data
      from all four time points were available for 82% of the children enrolled.
      Overall, 10% of the children had constant, severe trachoma, defined as severe
      trachoma at three or four examinations. The odds ratio for severe trachoma was
      1.9 for female children (95% confidence interval 1.3-2.7). Familial cattle
      ownership and having one or more siblings with trachoma at baseline were also
      significantly related to the odds of having severe trachoma. Children with a
      sustainably clean face had lower odds (odds ratio = 0.4, 95% confidence interval
      0.3-0.7). A subgroup of 10% of children in these hyperendemic communities always
      seemed to have severe trachoma, despite enrollment in a mass treatment campaign.
      Improved face-washing plus antibiotic treatment may decrease the likelihood that
      these children will be at risk for blinding complications in adulthood.

PMID- 8533750
TI  - T-lymphocyte subsets and prolonged diarrhea in young children from Guinea-Bissau.
AB  - In a community-based prospective study of 380 children conducted between 1987 and
      1990, the rate of diarrhea was significantly associated with percentage of CD8 T
      lymphocytes and the CD4:CD8 ratio. After adjustment for age and previous
      diarrhea, the relative incidence of diarrhea with a duration of > or = 7 days was
      2.10 (95% confidence interval (CI) 1.15-3.85) in children with 20-29.9% CD8 T
      cells and 3.41 (95% CI 1.29-9.01) in children with > or = 30% CD8 T-cells (in
      comparison with children who had less than 20% CD8 cells) (p for trend = 0.004).
      There was a nonsignificant tendency for rates of diarrhea of > or = 7 days to
      decrease according to increasing proportions of CD4 cells (p = 0.194). The
      authors found no significant association between T-cell subsets and diarrhea
      which resolved within 6 days. The association between the incidence of prolonged
      diarrhea and T-cell subset proportions could not be explained as a confounding
      effect of low weight, breastfeeding, or previous infection with measles or
      Cryptosporidium. However, other prior infections or micronutrient deficiencies
      may explain the findings, and these host factors may be significant targets in
      intervention against diarrheal diseases.

PMID- 8533751
TI  - Evaluation of birth cohort patterns in population disease rates.
AB  - Interpretation of trends in disease rates using conventional age-period-cohort
      analyses is made difficult by the lack of a unique set of parameters specifying
      any given model. Because of difficulties inherent in age-period-cohort models,
      neither the magnitude nor the direction of a linear trend in birth cohort effects
      or calendar period effects can be determined unambiguously. This leads to
      considerable uncertainty in making inferences regarding disease etiology based on
      birth cohort or calendar period trends. In this paper, the authors demonstrate
      that changes in the direction or magnitude of long term trends can be identified
      unequivocally in age-period-cohort analyses, and they provide parametric methods
      for evaluating such changes in trend within the usual Poisson regression
      framework. Such changes can have important implications for disease etiology.
      This is demonstrated in applications of the proposed methods to the investigation
      of birth cohort trends in female breast cancer mortality rates obtained from the
      National Center for Health Statistics for the United States (1970-1989) and from
      the World Health Organization for Japan (1955-1979).

PMID- 8533752
TI  - Optimal sampling strategies for two-stage studies.
AB  - The optimal allocation of available resources is the concern of every
      investigator in choosing a study design. The recent development of statistical
      methods for the analysis of two-stage data makes these study designs attractive
      for their economy and efficiency. However, little work has been done on deriving
      two-stage designs that are optimal under the kinds of constraints encountered in
      practice. The methods presented in this paper provide a means of deriving designs
      that will maximize precision for a fixed total budget or minimize the study cost
      necessary to achieve a desired precision. These optimal designs depend on the
      relative information content and the relative cost of gathering the first- and
      second-stage data. In place of the usual sample size calculations, the
      investigator can use pilot data to estimate the study size and second-stage
      sampling fractions. The gains in efficiency that can result from such carefully
      designed studies are illustrated here by deriving and implementing optimal
      designs using data from the Coronary Artery Surgery Study.

PMID- 8533753
TI  - Ancient DNA: how do you know when you have it and what can you do with it?

PMID- 8533754
TI  - New approaches to evaluating the genetic effects of the atomic bombs.

PMID- 8533755
TI  - Human beta-globin gene polymorphisms characterized in DNA extracted from ancient
      bones 12,000 years old.
AB  - Analyzing the nuclear DNA from ancient human bones is an essential step to the
      understanding of genetic diversity in current populations, provided that such
      systematic studies are experimentally feasible. This article reports the
      successful extraction and amplification of nuclear DNA from the beta-globin
      region from 5 of 10 bone specimens up to 12,000 years old. These have been typed
      for beta-globin frameworks by sequencing through two variable positions and for a
      polymorphic (AT) chi (T) gamma microsatellite 500 bp upstream of the beta-globin
      gene. These specimens of human remains are somewhat older than those analyzed in
      previous nuclear gene sequencing reports and considerably older than those used
      to study high-copy-number human mtDNA. These results show that the systematic
      study of nuclear DNA polymorphisms of ancient populations is feasible.

PMID- 8533756
TI  - Lack of effects of atomic bomb radiation on genetic instability of tandem
      repetitive elements in human germ cells.
AB  - In a pilot study to detect the potential effects of atomic bomb radiation on germ
      line instability, we screened 64 children from 50 exposed families and 60 from 50
      control families for mutations at six minisatellite loci by using Southern blot
      analysis with Pc-1, lambda TM-18, ChdTC-15, p lambda 3, lambda MS-1, and CEB-1
      probes. In the exposed families, one or both parents received a radiation dose >
      0.01 Sv. Among the 64 children, only one child had parents who were both exposed.
      Thus, of a total of 128 gametes that produced the 64 children, 65 gametes were
      derived from exposed parents and 63 were from unexposed parents, the latter being
      included in a group of 183 unexposed gametes used for calculating mutation rates.
      The average parental gonadal dose for the 65 gametes was 1.9 Sv. We detected a
      total of 28 mutations at the p lambda g3, lambda MS-1, and CEB-1 loci, but no
      mutations at the Pc-1, lambda TM-18, and ChdTC-15 loci. We detected 6 mutations
      in 390 alleles of the 65 exposed gametes and 22 mutations in 1098 alleles of the
      183 gametes from the unexposed parents. The mean mutation rate per locus per
      gamete in these six minisatellite loci was 1.5% in the exposed parents and 2.0%
      in the unexposed parents. We observed no significant difference in mutation rates
      in the children of the exposed and the unexposed parents (P = .37, Fisher's exact
      probability test).

PMID- 8533757
TI  - Novel inherited mutations and variable expressivity of BRCA1 alleles, including
      the founder mutation 185delAG in Ashkenazi Jewish families.
AB  - Thirty-seven families with four or more cases of breast cancer or breast and
      ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line
      mutations, four novel and eight previously observed, were detected in 16
      families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation
      and shared the same haplotype at eight polymorphic markers spanning approximately
      850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early
      onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred
      independently in two families. In one family, penetrance was complete, with
      females developing early-onset breast cancer or ovarian cancer and the male
      carrier developing prostatic cancer, whereas, in the other family, penetrance was
      incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two
      novel nonsense mutations led to the loss of mutant BRCA1 transcript in families
      with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt
      segment of the BRCA1 3'-UTR and 1.3 kb of genomic sequence including the putative
      promoter region were invariant by single-strand conformation analysis in 13
      families without coding-sequence mutations. Overall in our series, BRCA1
      mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7
      with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not
      tested for linkage. Three other families have positive lod scores for linkage to
      BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores
      for both BRCA1 and BRCA2.

PMID- 8533759
TI  - Phenylketonuria mutation analysis in Northern Ireland: a rapid stepwise approach.
AB  - We present a multistep approach for the rapid analysis of phenylketonuria (PKU)
      mutations. In the first step, three common mutations and a polymorphic short
      tandem repeat (STR) system are rapidly analyzed with a fluorescent multiplex
      assay. In the second step, minihaplotypes combining STR and VNTR data are used to
      determine rare mutations likely to be present in an investigated patient, which
      are then confirmed by restriction enzyme analysis. The remaining mutations are
      analyzed with denaturant gradient-gel electrophoresis and sequencing. The first
      two steps together identify both mutations in 90%-95% of PKU patients, and
      results can be obtained within 2 d. We have investigated 121 Northern Irish
      families with hyperphenylalaninemia, including virtually all patients born since
      1972, and have found 34 different mutations on 241 of the 242 mutant alleles.
      Three mutations (R408W, I65T, and F39L) account for 57.5% of mutations, while 14
      mutations occur with a frequency of 1%-6%. The present analysis system is
      efficient and inexpensive and is particularly well suited to routine mutation
      analysis in a diagnostic setting.

PMID- 8533758
TI  - Mutations of the microsomal triglyceride-transfer-protein gene in
      abetalipoproteinemia.
AB  - Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins
      constitute a major risk factor for the development of coronary heart disease. In
      the rare recessively inherited disorder abetalipoproteinemia (ABL) the production
      of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB
      gene. In the current study we have characterized the gene encoding a microsomal
      triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have
      identified a mutation of the MTP gene in both alleles of all individuals in a
      cohort of eight patients with classical ABL. Each mutant allele is predicted to
      encode a truncated form of MTP with a variable number of aberrant amino acids at
      its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1
      cells indicates that the C-terminal portion of MTP is necessary for triglyceride
      transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the
      894-amino-acid protein and a missense mutation of cysteine 878 to serine both
      abolished activity. These results establish that defects of the MTP gene are the
      predominant, if not sole, cause of hereditary ABL and that an intact carboxyl
      terminus is necessary for activity.

PMID- 8533760
TI  - Molecular pathology and haplotype analysis of Wilson disease in Mediterranean
      populations.
AB  - We analyzed mutations and defined the chromosomal haplotype in 127 patients and
      Mediterranean descent who were affected by Wilson disease (WD), 39 Sardinians, 49
      Italians, 33 Turks, and 6 Albanians. Haplotypes were derived by use of the
      microsatellite markers D13S301, D13S296, D13S297, and D13S298, which are linked
      to the WD locus. There were five common haplotypes in Sardinians, three in
      Italians, and two in Turks, which accounted for 85%, 32%, and 30% of the WD
      chromosomes, respectively. We identified 16 novel mutations: 8 frameshifts, 7
      missense mutations, and 1 splicing defect. In addition, we detected the
      previously described mutations: 2302insC, 3404delC, Arg1320ter, Gly944-Ser, and
      His1070Gin. Of the new mutations detected. two, the 1515insT on haplotype I and
      2464delC on haplotype XVI, accounted for 6% and 13%, respectively, of the
      mutations in WD chromosomes in the Sardinian population. Mutations H1070Q,
      2302insC, and 2533delA represented 13%, 8%, and 8%, respectively, of the
      mutations in WD chromosomes in other Mediterranean populations. The remaining
      mutations were rare and limited to one or two patients from different
      populations. Thus, WD results from some frequent mutations and many rare defects.

PMID- 8533761
TI  - Spectrum of mutations in the major human skeletal muscle chloride channel gene
      (CLCN1) leading to myotonia.
AB  - Autosomal dominant myotonia congenita and autosomal recessive generalized
      myotonia (GM) are genetic disorders characterized by the symptom of myotonia,
      which is based on an electrical instability of the muscle fiber membrane.
      Recently, these two phenotypes have been associated with mutations in the major
      muscle chloride channel gene CLCN1 on human chromosome 7q35. We have
      systematically screened the open reading frame of the CLCN1 gene for mutations by
      SSC analysis (SSCA) in a panel of 24 families and 17 single unrelated patients
      with human myotonia. By direct sequencing of aberrant SSCA conformers were
      revealed 15 different mutations in a total of 18 unrelated families and 13 single
      patients. Of these, 10 were novel (7 missense mutations, 2 mutations leading to
      frameshift, and 1 mutation predicted to affect normal splicing). In our overall
      sample of 94 GM chromosomes we were able to detect 48 (51%) mutant GM alleles.
      Three mutations (F413C), R894X, and a 14-bp deletion in exon 13) account for 32%
      of the GM chromosomes in the German population. Our finding that A437T is
      probably a polymorphism is in contrast to a recent report that the recessive
      phenotype GM is associated with this amino acid change. We also demonstrate that
      the R894X mutation may act as a recessive or a dominant mutation in the CLCN1
      gene, probably depending on the genetic background. Functional expression of the
      R894X mutant in Xenopus oocytes revealed a large reduction, but not complete
      abolition, of chloride currents. Further, it had a weak dominant negative effect
      on wild-type currents in coexpression studies. Reduction of currents predicted
      for heterozygous carriers are close to the borderline value, which is sufficient
      to elicit myotonia.

PMID- 8533762
TI  - A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44 Ala-->Gly), is
      the major polymorphic variant in tribal populations in India.
AB  - Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is usually found at high
      frequencies in areas of the world where malaria has been endemic. The frequency
      and genetic basis of G6PD deficiency have been studied in Africa, around the
      Mediterranean, and in the Far East, but little such information is available
      about the situation in India. To determine the extent of heterogeneity of G6PD,
      we have studied several different Indian populations by screening for G6PD
      deficiency, followed by molecular analysis of deficient alleles. The frequency of
      G6PD deficiency varies between 3% and 15% in different tribal and urban groups.
      Remarkably, a previously unreported deficient variant, G6PD Orissa (44 Ala-
      >Gly), is responsible for most of the G6PD deficiency in tribal Indian
      populations but is not found in urban populations, where most of the G6PD
      deficiency is due to the G6PD Mediterranean (188 Ser-->Phe) variant. The KmNADP
      of G6PD Orissa is fivefold higher than that of the normal enzyme. This may be due
      to the fact that the alanine residue that is replaced by glycine is part of a
      putative coenzyme-binding site.

PMID- 8533763
TI  - Haploinsufficiency of cytosolic serine hydroxymethyltransferase in the Smith
      Magenis syndrome.
AB  - Folate-dependent one-carbon metabolism is critical for the synthesis of numerous
      cellular constituents required for cell growth, and serine
      hydroxymethyltransferase (SHMT) is central to this process. Our studies reveal
      that the gene for cytosolic SHMT (cSHMT) maps to the critical interval for Smith
      Magenis syndrome (SMS) on chromosome 17p11.2. The basic organization of the cSHMT
      locus on chromosome 17 was determined and was found to be deleted in all 26 SMS
      patients examined by PCR, FISH, and/or Southern analysis. Furthermore, with
      respect to haploinsufficiency, cSHMT enzyme activity in patient lymphoblasts was
      determined to be approximately 50% that of unaffected parent lymphoblasts.
      Serine, glycine, and folate levels were also assessed in three SMS patients and
      were found to be within normal ranges. The possible effects of cSHMT hemizygosity
      on the SMS phenotype are discussed.

PMID- 8533765
TI  - Familial Klippel-Feil syndrome and paracentric inversion inv(8)(q22.2q23.3).
AB  - Klippel-Feil Syndrome (KFS) is characterized by congenital vertebral fusion
      believed to result from faulty segmentation along the embryo's developing axis.
      KFS appears to be a heterogeneous disease often associated with craniofacial
      malformation. Here we provide the first evidence of a familial KFS gene locus on
      8q, where an inv(8)(q22.2q23.3) has been found segregating with congenital
      vertebral fusion. The four-generation KF2-01 family present with dominant form of
      the KFS where the sequence of vertebral fusion was confined to the cervical spine
      (always including the C2-3 fusion and reduced expression of the C4-5 and C6-7
      fusions) in association with malformation of laryngeal cartilages and mild-to
      severe vocal impairment.

PMID- 8533764
TI  - A YAC contig encompassing the recessive Stargardt disease gene (STGD) on
      chromosome 1p.
AB  - Stargardt disease (STGD) and fundus flavimaculatus are infrequent autosomal
      recessive conditions characterized by a juvenile macular dystrophy and variable
      degrees of peripheral retinal changes. Linkage analysis performed in 47
      STGD/fundus flavimaculatus families demonstrated significant linkage to 13
      polymorphic DNA markers on chromosome 1p. The maximum combined two-point lod
      score was 32.7 (maximum recombination fraction [phi max] = .006) with the
      polymorphic marker D1S188. Our data demonstrate that STGD and fundus
      flavimaculatus are the same disorder clinically and genetically and provide
      further evidence for genetic homogeneity of this phenotype. Analysis of
      recombination events on disease chromosomes placed the STGD gene within a 4-cM
      interval between markers D1S435 and D1S236. A physical map was constructed of a
      YAC contig flanking STGD, from markers D1S500 to D1S495, and includes the
      critical interval delineated by historical recombinants. This contig spans
      approximately 31 cM, with one gap (3-5 cM) that is outside the 4-cM critical
      region. Localization of STGD to a single YAC contig will facilitate its
      positional cloning.

PMID- 8533766
TI  - Evidence for locus heterogeneity in autosomal dominant limb-girdle muscular
      dystrophy.
AB  - Limb-girdle muscular dystrophy (LGMD) is a diagnostic classification encompassing
      a broad group of proximal myopathies. A gene for the dominant form of LGMD
      (LGMD1A) has recently been localized to a 7-cM region of chromosome 5q between
      D5S178 and IL9. We studied three additional dominant LGMD families for linkage to
      these two markers and excluded all from localization to this region, providing
      evidence for locus heterogeneity within the dominant form of LGMD. Although
      patterns of muscle weakness were similar in all families studied, the majority of
      affected family members in the chromosome 5-linked pedigree have a dysarthric
      speech pattern, which is not present in any of the five unlinked families. The
      demonstration of heterogeneity within autosomal dominant LGMD is the first step
      in attempting to subclassify these families with similar clinical phenotypes on a
      molecular level.

PMID- 8533767
TI  - Fine mapping and haplotype analysis of the locus for congenital nephrotic
      syndrome on chromosome 19q13.1.
AB  - We have recently localized the gene for congenital nephrotic syndrome of the
      Finnish type (CNF) to chromosome 19q12-13.1. On the basis of observed
      recombination events, the gene was localized between markers
      D19S416/D19S425/D19S213/D19S208/D19S191 and D19S224. Here we have extended the
      mapping efforts, on the basis of a detailed physical map of the region. By means
      of three new polymorphic markers--D19S608, D19S609, and D19S610--developed in
      this study, the critical candidate region could be further restricted.
      Significant linkage disequilibrium was observed with markers D19S610, D19S608,
      D19S224, and D19S220, the strongest allelic association being 84% with marker
      D19S610 at 19q13.1. This suggests that the CNF gene locus lies in close proximity
      to marker D19S610. Combination of the informative markers revealed four main
      haplotype categories. Different geographic distribution was observed between
      these haplotype groups when they were placed on the map of finland according to
      the birthplaces of grandparents.

PMID- 8533768
TI  - Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin
      effect.
AB  - A susceptibility gene on chromosome 18 and a parent-of-origin effect have been
      suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear
      families selected for apparent unilineal transmission of the BPAD phenotype, by
      using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was
      tested with affected-sib-pair and LOD score methods under two definitions of the
      affected phenotype. The affected-sibpair analyses indicated excess allele sharing
      for markers on 18p within the region reported previously. The greatest sharing
      was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006).
      In addition, excess sharing of the paternally, but not maternally, transmitted
      alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib
      pairs were concordant for paternally transmitted alleles, and 21 pairs were
      discordant (P = 0004). The evidence for linkage to loci on both 18p and 18q was
      strongest in the 11 paternal pedigrees, i.e., those in which the father or one of
      the father's sibs is affected. In these pedigrees, the greatest allele sharing
      (81%; P = .00002) and the highest LOD score (3.51; phi = 0.0) were observed at
      D18S41. Our results provide further support for linkage of BPAD to chromosome 18
      and the first molecular evidence for a parent-of-origin effect operating in this
      disorder. The number of loci involved, and their precise location, require
      further study..

PMID- 8533769
TI  - The relationship between paternal age, sex ratios, and aneuploidy frequencies in
      human sperm, as assessed by multicolor FISH.
AB  - We studied the frequencies of X- and Y-chromosome-bearing sperm, diploidy and
      disomy for chromosomes 1, 12, X, and Y in sperm from 10 normal men aged 21-52
      years, to determine whether there was any relationship between donor age and any
      of these variables. Multicolor FISH was used to control for lack of probe
      hybridization and to distinguish diploid sperm from disomic sperm. A minimum of
      10,000 sperm per donor was evaluated for each chromosome, for a total of 225,846
      sperm studied. Sperm were considered disomic if two fluorescent signals were
      separated by a minimal distance of one signal domain. The mean frequencies of X-
      and Y-bearing sperm were 50.1% and 49.0%, respectively; not significantly
      different from 50%. There was no correlation between paternal age and "sex ratio"
      in sperm. Similarly, there was no association between the frequency of diploid
      sperm (mean, .16%; range, .06-.42%) and donor age. For disomy frequencies, there
      was no relationship between donor age and disomy 12 (mean, .16%; range, .10%
      .25%), XX (mean, .07%; range, .03%-.17%), and XY sperm (mean, .16%; range, .08%
      .24%). There was a significant increase in the frequency of YY sperm (P = .04;
      mean, .18%; range, .10%-.43%) and disomy 1 sperm (P = .01; mean, .11%; range,
      .05%-.18%) with donor age. In summary, our results do not support a correlation
      between paternal age and sex ratio or diploidy.

PMID- 8533770
TI  - Gonadoblastoma: molecular definition of the susceptibility region on the Y
      chromosome.
AB  - Using sequence-tagged sites we have performed deletion mapping of the Y
      chromosome in sex-reversed female patients with a Y chromosome and
      gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was
      sublocalized to a small region near the centromere of the Y chromosome. We
      estimate the size of the GBY critical region to be approximately 1-2 Mb. Our
      analysis also indicates that copies of two dispersed Y-linked gene families, TSPY
      (testis-specific protein, Y-encoded) and YRRM (Y-chromosome RNA recognition
      motif) are present in all patients and that copies of TSPY but not YRRM fall
      within the GBY critical region as formally defined by deletion mapping. Two tumor
      samples showed expression of both genes and in one patient this expression was
      limited to a unilateral gonadoblastoma but absent in the contralateral streak
      gonad. Although our results do not directly implicate TSPY or YRRM in the
      etiology of the tumor, they raise the issue of whether there is one GBY gene in
      the critical region or possibly multiple GBY loci dispersed on the Y chromosome.

PMID- 8533771
TI  - Expansion of the CGG repeat in fragile X in the FMR1 gene depends on the sex of
      the offspring.
AB  - Analysis of 139 mother-to-offspring transmissions of fragile X CGG triplet
      repeats revealed that the repeat expansion is enhanced in mother-to-son
      transmissions compared with mother-to-daughter transmissions. Evidence has been
      based on analysis of mother-offspring differences in the size of repeat (in kb),
      as well as on comparisons between proportions of male and female offspring with
      premutations, and full mutations, inherited from mothers carrying a premutation.
      Mean difference in the repeat size from mother-son transmissions was 1.45 kb,
      compared with mother-daughter transmissions of 0.76 kb. The difference is due
      primarily to a greater proportion of male than female offspring with full
      mutation from the premutation mothers and also to a higher frequency of reduction
      in repeat size from mothers to daughters than from mothers to sons. Our findings
      suggest the possibility of an interaction of the normal X homologue in a female
      zygote with the FMR1 sequence on the fragile X during replication to account for
      the lower level of expansion in mother-to-daughter transmissions relative to
      mother-to-son transmissions.

PMID- 8533772
TI  - Population dynamics of a meiotic/mitotic expansion model for the fragile X
      syndrome.
AB  - A model to explain the mutational process and population dynamics of the fragile
      X syndrome is presented. The mutational mechanism was assumed to be a
      multipathway, multistep process. Expansion of CGG repeats was based on an
      underlying biological process and was assumed to occur at two time points:
      meiosis and early embryonic development (mitosis). Meiotic expansion was assumed
      to occur equally in oogenesis and spermatogenesis, while mitotic expansion was
      restricted to somatic, or constitutional, alleles of maternal origin. Testable
      hypotheses were predicted by this meiotic/mitotic model. First, parental origin
      of mutation is predicted to be associated with the risk of a woman to have a full
      mutation child. Second, "contractions" seen in premutation male transmissions are
      predicted not to be true contractions in repeat size, but a consequence of the
      lack of mitotic expansion in paternally derived alleles. Third, a portion of full
      mutation males should have full-mutation alleles in their sperm, due to the lack
      of complete selection against the full-mutation female. Fourth, a specific
      premutation-allele frequency distribution is predicted and differs from that
      based on models assuming only meiotic expansion. Last, it is predicted that
      approximately 65 generations are required to achieve equilibrium, but this
      depends greatly on the expansion probabilities.

PMID- 8533773
TI  - Segregation and linkage analysis of serum angiotensin I-converting enzyme levels:
      evidence for two quantitative-trait loci.
AB  - Human serum angiotensin I-converting enzyme (ACE) levels vary substantially
      between individuals and are highly heritable. Segregation analysis in European
      families has shown that more than half of the total variability in ACE levels is
      influenced by quantitative-trait loci (QTL). One of these QTLs is located within
      or close to the ACE locus itself. Combined segregation/linkage analysis in a
      series of African Caribbean families from Jamaica shows that the ACE insertion
      deletion polymorphism is in moderate linkage disequilibrium with an ACE-linked
      QTL. Linkage analysis with a highly informative polymorphism at the neighboring
      growth-hormone gene (GH) shows surprisingly little support for linkage (LOD score
      [Z] = 0.12). An extended analysis with a two-QTL model, where an ACE-linked QTL
      interacts additively with an unlinked QTL, significantly improves both the fit of
      the model (P = .002) and the support for linkage between the ACe-linked QTL
      interacts additively with an unlinked QTL, significantly improves both the fit of
      the model (P = .002) and the support for linkage between the ACe-linked QTL and
      GH polymorphism (Z = 5.0). We conclude that two QTLs jointly influence serum ACE
      levels in this population. One QTL is located within or close to the ACE locus
      and explains 27% of the total variability; the second QTL is unlinked to the ACE
      locus and explains 52% of the variability. The identification of the molecular
      mechanisms underlying both QTLs is necessary in order to interpret the role of
      ACE in cardiovascular disease.

PMID- 8533774
TI  - Discordant patterns of linkage disequilibrium of the peptide-transporter loci
      within the HLA class II region.
AB  - Disequilibrium between genetic markers is expected to decline monotonically with
      recombinational map distance. We present evidence from the HLA class II region
      that seems to violate this principle. Pairwise disequilibrium values were
      calculated from six loci ranging in physical separation from 15 kb to 550 kb. The
      histocompatibility loci DRB1, DQA1, and DQB1, located on the distal end of the
      class II region, behave as a single evolutionary unit within which extremely high
      linkage disequilibrium exists. Lower but still significant levels of
      disequilibrium are present between these loci and DPB1, located at the proximal
      edge of the HLA complex. The peptide-transporter loci TAP1 and TAP2, located in
      the intervening region, reveal no disequilibrium with each other and low or
      negligible disequilibrium with the flanking loci. The action of two genetic
      process is required to account for this phenomenon: a recombinational hotspot
      operating between TAP1 and TAP2, to eliminate disequilibrium between these loci,
      and at the same time selection operating on particular combinations of alleles
      across the DR-DP region, to create disequilibrium in the favored haplotypes. The
      forces producing the patterns of disequilibrium observed here have implications
      for the mapping of train loci and disease genes: markers of TAP1, for example,
      would give a false impression as to the influence of DPB1 on a trait known to be
      associated with DQB1.

PMID- 8533775
TI  - Evolution of haplotypes at the DRD2 locus.
AB  - We present here the first evolutionary perspective on haplotypes at DRD2, the
      locus for the dopamine D2 receptor. The dopamine D2 receptor plays a critical
      role in the functioning of many neural circuits in the human brain. If
      functionally relevant variation at the DRD2 locus exists, understanding the
      evolution of haplotypes on the basis of polymorphic sites encompassing the gene
      should provide a powerful framework for identifying that variation. Three DRD2
      polymorphisms (TaqI "A" and "B" RFLPs and the (CA)n short tandem repeat
      polymorphic in all the populations studied, and they display strong and
      significant linkage disequilibria with each other. The common haplotypes for the
      two TaqI RFLPs are separately derived from the ancestral haplotype but predate
      the spread of modern humans around the world. The knowledge of how the various
      haplotypes have evolved, the allele frequencies of the haplotypes in human
      populations, and the physical relationships of the polymorphisms to each other
      and to the functional parts of the gene should now allow proper design and
      interpretation of association studies.

PMID- 8533776
TI  - Estimates of the gene frequency of BRCA1 and its contribution to breast and
      ovarian cancer incidence.
AB  - The majority of multiple-case families that segregate both breast and ovarian
      cancer in a dominant fashion are due to mutations in the BRCA1 gene on chromosome
      17q. In this paper, we have combined penetrance estimates for BRCA1 with the
      results of two population-based genetic epidemiological studies to estimate the
      gene frequency of BRCA1. On the assumption that the excess risk of ovarian cancer
      in first degree relatives of breast cancer patients and the breast cancer excess
      in relatives of ovarian cancer patients are both entirely accounted for by BRCA1,
      we estimate that the BRCA1 gene frequency is 0.0006 (95% confidence interval
      [O.002-0.002]) and that the proportion of breast cancer cases in the general
      population due to BRCA1 is 5.3% below age 40 years, 2.2% between ages 40 and 49
      years, and 1.1% between ages 50 and 70 years. The corresponding estimates for
      ovarian cancer are 5.7%, 4.6%, and 2.1%, respectively. Our results suggest that
      the majority of breast cancer families with less than four cases and no ovarian
      cancer are not due to rare highly penetrant genes such as BRCA1 but are more
      likely to be due either to chance or to more common genes of lower penetrance.

PMID- 8533777
TI  - The origins of the Polynesians: an interpretation from mitochondrial lineage
      analysis.
AB  - Using mitochondrial lineage analysis of 1,178 individuals from Polynesia, the
      western Pacific, and Taiwan, we show that the major prehistoric settlement of
      Polynesia was from the west and involved two or possibly three genetically
      distinct populations. The predominant lineage group, accounting for 94% of
      Polynesian mtDNA, shares a 9-bp COII/tRNA(Lys) intergenic deletion and
      characteristic control region transition variants, compared to the Cambridge
      reference sequence. In Polynesia, the diversity of this group is extremely
      restricted, while related lineages in Indonesia, the Philippines, and Taiwan are
      increasingly diverse. This suggests a relatively recent major eastward expansion
      into Polynesia, perhaps originating from Taiwan, in agreement with archeological
      and linguistic evidence, but which experienced one or more severe population
      bottlenecks. The second mitochondrial lineage group, accounting for 3.5% of
      Polynesian mtDNA haplotypes, does not have the 9-bp deletion and its
      characterized by an A-C transversional variant at nt position 16265. Specific
      oligonucleotides for this variant were used to select individuals from the
      population sample who, with other sequences, show that the Polynesian lineages
      were part of a diverse group in Vanuatu and Papua New Guinea. The very low
      overall diversity of both lineage groups in Polynesia suggests there was severe
      population restriction during the colonization of remote Oceania. A third group,
      represented by only four individuals (0.6%) in Polynesia but also present in the
      Philippines, shares variants at nt positions 16172 and 16304. Two Polynesians had
      unrelated haplotypes matching published sequences from native South Americans,
      which may be the first genetic evidence of prehistoric human contact between
      Polynesia and South America.

PMID- 8533778
TI  - The relative efficiency of the Hardy-Weinberg equilibrium-likelihood and the
      conditional on parental genotype-likelihood methods for candidate-gene
      association studies.
AB  - Selecting a control group that is perfectly matched for ethnic ancestry with a
      group of affected individuals is a major problem in studying the association of a
      candidate gene with a disease. This problem can be avoided by a design that uses
      parental data in place of nonrelated controls. Schaid and Sommer presented two
      new methods for the statistical analysis using this approach: (1) a likelihood
      method (Hardy-Weinberg equilibrium [HWE] method), which rests on the assumption
      that HWE holds, and (2) a conditional likelihood method (conditional on parental
      genotype [CPG] method) appropriate when HWE is absent. Schaid and Sommer claimed
      that the CPG method can be more efficient than the HWE method, even when
      equilibrium holds. It can be shown, however that in the equilibrium situation the
      HWE method is always more efficient than the CPG method. For a dominant disease,
      the differences are slim. But for a recessive disease, the CPG method requires a
      much larger sample size to achieve a prescribed power than the HWE method.
      Additionally, we show how the relative risks for the various candidate-gene
      genotypes can be estimated without relying on iterative methods. For the CPG
      method, we represent an asymptotic power approximation that is sufficiently
      precise for planning the sample size of an association study.

PMID- 8533779
TI  - Are moment bounds on the recombination fraction between a marker and a disease
      locus too good to be true? Allelic association mapping revisited for simple
      genetic diseases in the Finnish population.
AB  - In the past several years, allelic association has helped map a number of rare
      genetic diseases in the human genome. A commonly used upper bound on the
      recombination fraction between the disease gene and an associated marker is known
      to be biased downward, so there is the possibility that an investigator could be
      misled. This upper bound is based on a moment equation that can be derived within
      the context of a Poisson branching process, so its performance can be compared
      with a recently proposed likelihood bound. We show that the confidence level of
      the moment upper bound is much lower than expected, while the confidence level of
      the likelihood bound is in line with expectation. The effects of mutation at
      either the marker or disease locus on the upper bounds are also investigated.
      Results indicate that mutation is not an important force for typical mutation
      rates, unless the recombination fraction between the marker and disease locus is
      very small or the disease allele is very rare in the general population. Finally,
      the impact of sample size on the likelihood bound is investigated. The results
      are illustrated with data on 10 simple genetic diseased in the Finnish
      population.

PMID- 8533780
TI  - ACMG statement. Statement on storage and use of genetic materials. American
      College of Medical Genetics Storage of Genetics Materials Committee.

PMID- 8533781
TI  - The 14484 ND6 mtDNA mutation in Leber hereditary optic neuropathy does not affect
      fibroblast complex I activity.

PMID- 8533782
TI  - Molecular basis of spinal muscular atrophy in Chinese.

PMID- 8533783
TI  - Urinary pyridinoline cross-links in Ehlers-Danlos syndrome type VI.

PMID- 8533784
TI  - Pyridinium cross-links in heritable disorders of collagen.

PMID- 8533785
TI  - No difference in the parental origin of susceptibility HLA class II haplotypes
      among Norwegian patients with insulin-dependent diabetes mellitus.

PMID- 8533786
TI  - Medical school core curriculum in genetics.

PMID- 8533787
TI  - Budget cuts are grave to NIOSH.

PMID- 8533788
TI  - Respiratory cancer and other chronic disease mortality among silicotics in
      California.
AB  - Silicotics have increased mortality from tuberculosis (TB) and from nonmalignant
      respiratory diseases (NMRD), including silicosis and silicotuberculosis. Since
      the publication of the International Agency for Research on Cancer monograph in
      1987 indicating that silica was a probable human carcinogen, there has been an
      extensive debate about the cancer risks among silicotics. The authors identified
      590 claims for silicosis among a registry of lung diseases compiled from
      California Workers' Compensation cases from 1945 to 1975. Using state vital
      records, we determined the mortality risks from 1946 to 1991. Our findings
      confirmed that these claimants had a significantly elevated risk for all causes
      of death with a standardized mortality ratio (SMR) of 1.30 (95% confidence
      interval [CI] = 1.18, 1.43); TB had a SMR of 56.35 (95% CI = 41.10, 75.40) and
      NMRD a SMR of 3.80 (95% CI = 3.11, 4.60). Cancers of the trachea, bronchus, and
      lung had a SMR of 1.90 (95% CI = 1.35, 2.60). For malignancies of the large
      intestine, there was a previously unreported SMR of 2.08 (95% CI = 1.14, 3.50).
      Mortality from all diseases of the heart was significantly less than expected
      with a SMR of 0.68 (95% CI = 0.55, 0.83); cancers of the prostate and lymphatic
      system were also significantly low with SMRs of 0.26 (95% CI = 0.03, 0.94) and
      0.17 (95% CI = 0.04, 0.97), respectively. Workers with silicosis should be warned
      about these chronic disease risks, and prevention efforts to control occupational
      silica dust exposure should become a higher priority.

PMID- 8533789
TI  - Cross-sectional follow-up of a flu-like respiratory illness among fiberglass
      manufacturing employees: endotoxin exposure associated with two distinct
      sequelae.
AB  - Over a period of 10 years, employees in a manufacturing plant experienced
      sporadic flu-like episodes after work in a basement containing a recirculated
      washwater mist. We report a cross-sectional study to define the flu-like illness
      and bioaerosol exposures. High concentrations of gram-negative bacteria (GNB) (>
      10(7) cfu/ml) and endotoxin (range 34-46 micrograms/ml) were found in the water.
      Mist contained > 10(3) cfu/m3 of GNB, and endotoxin up to 13,900 to 27,800 ng/m3.
      Few fungi and thermotolerant Bacillus species and no Actinomycetes, Legionella
      species, or amoeba were found in washwater. Airborne levels of fungi were of the
      same species and magnitudes as outdoor samples. Subjects volunteered (n = 28)
      because of a history of flu-like symptoms or were randomly selected (n = 102)
      from workers with and without current exposure to the basement. No acute cases
      were examined. Cases did not fulfill criteria for hypersensitivity pneumonitis
      (HP) and high levels of IgG antibodies to water-borne antigens were not observed.
      However, among 20 subjects indicating a history of severe flu-like episodes
      (severe basement flu, SBF), diffusion capacity (DLCO) was significantly lower (p
      = 0.015) than among other workers. The prevalence of SBF was independent of
      smoking. Cases occurred in clusters, and SBF was more common among workers with
      intermittent exposure to the basement (19 cases) than with daily exposure (1
      case). These findings suggest that SBF and associated chronically depressed DLCO
      resulted from toxic injury following high-level endotoxin exposure. Asthma was
      prevalent in the study population, particularly among employees with daily,
      rather than intermittent, exposure to endotoxin-containing mist (odds ratio 6.7,
      p = 0.02). Thus, endotoxin exposure in this study was associated with two
      distinct sequelae depending on the temporal pattern of exposure.

PMID- 8533790
TI  - Asbestos bodies in lung tissue following exposure to crocidolite.
AB  - A series of 206 necropsies in Western Australia (WA) have had routine counts made
      of asbestos bodies in samples of lung tissue using conventional light microscopy.
      Thirty-two cases had worked in the asbestos industry at Wittenoom, WA and (log)
      counts of asbestos bodies in their lung tissue correlated well with estimates of
      their (log) cumulative airborne exposure to crocidolite fibers (r = 0.60). There
      was no association between the number of asbestos bodies and time since exposure
      to asbestos ceased. In subjects without known exposure to asbestos, there was a
      weak but nonsignificant increase in number of asbestos bodies with increasing
      age, with 26% of cases having no asbestos bodies present. It is concluded that
      the relatively simple technique of light microscopy for counting of asbestos
      bodies in lung tissue provides a reliable indication of the level of past
      occupational exposure to crocidolite in subjects whose exposure has been only to
      crocidolite. This could be extremely useful in follow-up studies of cohorts that
      lack reliable measures of airborne exposure to crocidolite asbestos.

PMID- 8533791
TI  - Altered partition of T cell subsets in the peripheral blood of healthy workers
      exposed to flour dust.
AB  - Occupational exposure to organic compounds can induce obvious immunological
      disorders or more subtle modifications. We investigated peripheral blood
      lymphocyte subsets in 34 bakers and 82 millers exposed to wheat flour dust, and
      51 salt factory workers. Significantly decreased levels of CD4+, CD8+, CD57+ and
      CD8+/57+ cells were noted in mill workers, and of CD57+ cells in bakers. CD29+
      and CD4+/CD29+ cells were significantly lower in millers, CD4+/CD45RA+ cells
      higher in all exposed workers. The lower numbers of positive cells noted in
      millers appeared associated to significantly higher (p < 0.001) levels of CD29
      and CD45RA expression as measured by fluorescence intensity. These data are
      opposite to those previously reported in asthmatic workers exposed to flour dust.
      Since the individuals tested here were clinically healthy, the alterations of T
      cell subsets observed could be interpreted as a successful attempt at
      immunoregulation maintaining homeostasis.

PMID- 8533792
TI  - Development of a questionnaire in Spanish on neurotoxic symptoms.
AB  - A questionnaire in Spanish (with yes/no answers) was developed in order to study
      effects of neurotoxic agents in groups of workers in Nicaragua. Since many
      workers in Latin America are illiterate, the questions were read to the subjects.
      The questionnaire initially contained 34 questions, which were reduced to 16
      after studying whether the questions were interpreted in the intended way by the
      subjects, whether the answers were reasonably reproducible over a 3-week period,
      and whether the questions discriminated between groups exposed to different
      neurotoxic agents (mercury, lead, organic solvents, and organophosphate
      insecticides) and nonexposed groups. In total, 851 male workers in Nicaragua and
      Venezuela participated in the evaluation. The questionnaire is submitted for use
      in the monitoring of groups exposed to neurotoxic agents, particularly in Latin
      America. The authors welcome further evaluation.

PMID- 8533793
TI  - Musculoskeletal problems among Ontario dental hygienists.
AB  - Two U.S. surveys suggested that dental hygienists (DHs) may suffer from carpal
      tunnel syndrome (CTS), but these studies did not use validated questionnaires,
      adjust for confounders, or include external controls. We conducted a
      questionnaire survey of all 2,142 DHs belonging to the Ontario Dental Hygienists'
      Association, and a referent group of 305 dental assistants (DAs), who do not
      scale teeth. The Standardized Nordic Questionnaire was used as the basis for
      asking about musculoskeletal symptoms. The response rates in the two groups were
      identical. Of the DHs, 7.0% had been told by a physician since starting work that
      they had CTS, but only 1 of 65 had received workers' compensation. Compared to
      the DAs, after adjusting for age the DHs were 5.2 times (95% confidence interval
      [CI] 0.9-32) more likely to have been told they had CTS and 3.7 times (95% CI 1.1
      11.9) more likely to meet a CTS case definition. The DHs were also 2.5 (95% CI
      1.6-3.9), 2.8 (95% CI 1.8-4.4), and 1.8 (95% CI 1.2-2.7) times more likely to
      report hand/wrist, shoulder, and neck problems in the past 12 months,
      respectively, but were less likely to report low back trouble. In internal
      analyses among DHs using logistic regression models, the number of heavy calculus
      patients per day, "clock" position around the dental chair, and years in practice
      were significant predictors of CTS. Days worked per week (but not heavy calculus
      patients), time with the trunk rotated, and years of practice were significant
      predictors of reported shoulder trouble in the past 12 months. Given that there
      are more than 9,000 DHs in Canada and about 100,000 in the United States, these
      findings suggest an important public health problem. They highlight the need to
      inform DHs during training and continuing education about musculoskeletal
      problems in general and CTS in particular. Attention should be directed to areas
      such as work station design, posture, treating patients with heavy calculus, and
      scheduling rest periods.

PMID- 8533794
TI  - Inflammatory markers in nasal lavage fluid from Industrial Arts teachers.
AB  - Exposure to wood dust can cause allergic and nonallergic rhinitis. Inflammatory
      markers [cells, albumin, tryptase, and eosinophil cationic protein (ECP)] were
      examined in nasal lavage fluid (NAL) sampled from 24 Industrial Arts (IA)
      teachers exposed to wood dust and other irritants and from 24 control subjects.
      The IA teachers had more nasal complaints but they did not differ significantly
      from the controls regarding ECP concentration (median 4.1 and 4.7 micrograms/L,
      respectively), albumin concentration (median 30.7 and 20.7 g/L), and percentage
      of neutrophils (median 56 and 34) in NAL. Tryptase was not detected. No marked
      inflammation was thus found, but the albumin concentration was higher in subjects
      reporting nasal stuffiness. In the IA teachers, a relationship between the
      percentage of neutrophils and the number of classes during the working week was
      found (Spearman's rank correlation coefficient 0.53, p < 0.01) indicating a
      possibility of wood-dust-related inflammatory effects on the nasal mucosa.

PMID- 8533795
TI  - Incidence of farm-work-related acute injury in a defined population.
AB  - To determine occurrence and sources of farm-work-related injury, we conducted a
      population-based, prospective study in a large clinic and hospital serving a
      defined rural area. The population at risk was identified through a unique
      demographic and medical records linkage system and a special agricultural census.
      Cases were 510 individuals who sought inpatient or outpatient care from May 1990
      through April 1992 from a physician or chiropractor for harm resulting from acute
      exposure to energy. One per 31 farm residents was treated annually for a farm
      work-related injury. Eight percent of these cases were hospitalized. Animals were
      the most frequent source of injury. Severity did not differ between cases
      associated with animals, machinery, falls, or chemicals. Thirty-eight percent of
      farm-work-related injury cases occurred in nonfarm residents. Injury risk was 2.5
      times greater among dairy farm residents than among nondairy farm residents,
      352.0 vs. 141.0 cases per 10,000 person-years, respectively. Adult male farm
      residents had 556.9 injuries per 10,000 person-years and 21.3 injuries per
      million hours of farm work.

PMID- 8533796
TI  - Farm-work hazard prevention efforts by school-based agricultural education
      instructors.
AB  - OBJECTIVE: To assess current prevention efforts, we examined agricultural work
      related safety and health activities by school-based agricultural education
      instructors in Wisconsin. METHODS: Questionnaires were administered to 284 high
      school agricultural education instructors. RESULTS: Instructors taught
      agricultural safety and health to 61.5 students during 20.4 hours during the
      previous year. Extension agents were used most often as resources during
      preparation and presentation of coursework. Only a minority of instructors
      (13.6%) agreed that modifying the work to eliminate hazards should be emphasized
      over training people to work safely around hazards. After issues of time
      pressures and lack of student interest, the most important problems the
      instructors felt they faced were the needs for materials and other resources.
      CONCLUSION: Safety education alone is unlikely to reduce injuries unless unsafe
      conditions are modified. Instructors need to emphasize teaching of skills in
      hazard recognition, identification, and control. Instructors felt they could be
      more effective with better materials and more time for injury and disease
      prevention.

PMID- 8533797
TI  - Monozygotic twins discordant for the Russell-Silver syndrome.
AB  - Russell-Silver syndrome (RSS) is a pattern of malformation characterized by
      intrauterine and postnatal growth retardation, limb asymmetry, triangular face,
      and hypospadias. We report on a patient, from a triplet pregnancy, who was one of
      identical male twins discordant for RSS. R.B. was a 710-g male born at 33 weeks
      of gestation, with hypospadias, chordee, and undescended testes. He had a normal
      46,XY karyotype and no renal abnormalities. Female triplet A weighed 1,843 g, and
      male triplet B weighed 1,920 g. Both had normal physical findings and neonatal
      period. R.B. was first seen by us at age 6 7/12 years with short stature,
      triangular and asymmetric face, lower limb length discrepancy, and surgically
      repaired genital anomalies. Growth hormone testing results were normal. At age 8
      7/12 years the brothers appeared physically identical except for size, with a
      height differential of 114.25 vs. 121.5 cm. Testing to establish biological
      zygosity was performed using VNTR (variable number tandem repeat) DNA probes
      YNH24 (D2S44), CMM101 (D14S13), EFD52 (D17S26), TBQ7 (D10S28), and 3'HVR
      (D16S85), PCR loci MCT118 (D1S80), and HLA-DQ alpha. These data indicate a >
      99.99% probability of triplets B and C being monozygotic twins. While most
      occurrences of RSS are sporadic, familial cases suggesting autosomal dominance
      have been reported. Three other cases of probable monozygotic twins with RSS have
      been described. The significance of this confirmation of discordance in
      determining the cause of RSS is discussed.

PMID- 8533798
TI  - Congenital healed cleft lip.
AB  - Congenital "healed" cleft lip (CHCL) is an unusual anomaly including a paramedian
      "scar" of the upper lip, which appears as if a typical cleft lip has been
      corrected in utero. The CHCL is frequently associated with an ipsilateral notch
      in the vermilion, and "collapsed" nostril. Twenty-five CHCL cases are presented,
      eighteen of which were an isolated malformation found among the 3,950,715 births
      examined in two similar birth defect registries: ECEMC in Spain and ECLAMC in
      Latin America. Like open cleft lip, of which it seems to be a variant, CHCL is
      most frequently seen among males (14/18 isolated cases), it preferentially
      affects the left side (10/18 cases), and it segregated together with cleft lip in
      one family. The five CHCL cases with other congenital anomalies included: two
      cases with hydrocephalus, two VACTERL associations, and one atypical oblique
      facial cleft infant with single umbilical artery. CHCL may result from a
      defective fusion of the frontonasal and maxillary processes (before week 7 of
      embryonic life), or from a spontaneously repaired open cleft lip, later on. In
      either way, these cases heal with a visible scar, and the pre-occurrence of CHCL
      in two families suggests a familial predisposition to this phenomenon.

PMID- 8533799
TI  - Apparently new "anophthalmia-plus" syndrome in sibs.
AB  - The index patient of this report is a 17-week-gestation female fetus with
      bilateral anophthalmia, bilateral cleft lip/cleft palate, macrotia with bilateral
      lateral facial cleft, large open sacral neural tube defect, and uterus unicornis.
      Parents were normal and nonconsanguineous with an unremarkable family history.
      Their first child, a 4-year-old boy, is normal. The second child, a 2 1/2-year
      old boy, has bilateral anophthalmia and an abnormal left ear with absent lobule
      as the sole additional anomaly. These 2 sibs seem to be the first examples of a
      new "anophthalmia-plus" syndrome apparently inherited as autosomal-recessive.

PMID- 8533800
TI  - Mutations in PAX3 that cause Waardenburg syndrome type I: ten new mutations and
      review of the literature.
AB  - Waardenburg syndrome (WS) is an autosomal-dominant disorder characterized by
      sensorineural hearing loss, dystopia canthorum, and pigmentary disturbances, and
      it represents the most common form of inherited deafness in infants. WS type I is
      characterized by the presence of dystopia canthorum, while individuals with WS
      type II have normally-located canthi. WS type III is similar to WS type I but is
      also characterized by musculoskeletal abnormalities. Defects in the PAX3 gene, a
      transcription factor expressed during embryonic development, have been shown to
      cause WS types I and III in several families. In contrast, mutations in PAX3 do
      not cause WS type II, and linkage of the disease to other chromosomal regions has
      been demonstrated. We describe 10 additional mutations in the PAX3 gene in
      families with WS type I. Eight of these mutations are in the region of PAX3,
      where only one mutation has been previously described. These mutations, together
      with those previously reported, cover essentially the entire PAX3 gene and
      represent a wide spectrum of mutations that can cause WS type I. Thus far, all
      but one of the mutations are private; only one mutation has been reported in two
      apparently unrelated families. Our analysis thus far demonstrates little
      correlation between genotype and phenotype; deletions of the entire PAX3 gene
      result in phenotypes indistinguishable from those associated with single-base
      substitutions in the paired domain or homeodomain of PAX3. Moreover, two similar
      mutations in close proximity can result in significantly different phenotypes, WS
      type I in one family and WS type III in another.

PMID- 8533802
TI  - Distal arthrogryposis type IIB: further clinical delineation and 54-year follow
      up of an index case.
AB  - Distal arthrogryposis IIB is characterized by contractures of the distal joints
      (especially of the fingers and toes) and ptosis. We recently encountered a father
      and son with these manifestations. The father was reported 54 years ago as a case
      of amyoplasia congenita (arthrogryposis multiplex congenita). Both father and son
      have distal joint contractures, most severe in the hands and feet, as well as
      ptosis and ophthalmoplegia. In addition, these patients have an unusual
      distribution of hair loss, and conical teeth. Whether these latter findings are
      related to the type of distal arthrogryposis present in this family is not known.
      In spite of their physical limitations both father and son have maintained an
      active life-style.

PMID- 8533801
TI  - Alopecia/mental retardation syndrome.
AB  - We report on an African-American patient with alopecia universalis, microcephaly,
      hypogonadism, and mental and growth retardation, and compare his phenotype to
      others with recessive alopecia/mental retardation syndromes in the literature.
      Our patient represents the first case reported from nonconsanguineous African
      American parents.

PMID- 8533803
TI  - Linkage of preaxial polydactyly type 2 to 7q36.
AB  - We have characterized a 6-generation North American Caucasian kindred segregating
      one form of preaxial polydactyly type 2 (PPD-2). We demonstrate linkage to the
      7q36 region and describe a submicroscopic telomeric chromosomal deletion in phase
      with the PPD-2 phenotype. Recently, several kindreds segregating triphalangeal
      thumb (TPT) with and without associated hand anomalies (syndactyly and/or
      postaxial polydactyly) have also been linked to the subtelomeric region of
      chromosome 7q [Heutink et al., 1994: Nat Genet 6:287-291; Tsukurov et al., 1994:
      Nat Genet 6:282-286]. We demonstrate by haplotype analysis that our North
      American pedigree represents a PPD allele that is independent of the founder PPD
      allele present in the previously described kindreds.

PMID- 8533804
TI  - Microdontia with severe microcephaly and short stature in two brothers:
      osteodysplastic primordial dwarfism with dental findings.
AB  - Two brothers from a black family had microcephaly, short stature, and generalized
      microdontia. Endocrine and chromosome studies were normal, and mild skeletal
      manifestations were present. The patients may represent a distinct dental
      skeletal dysplasia, possibly osteodysplastic primordial dwarfism type II.
      Attention to dental manifestations in similar cases may be useful for
      classification.

PMID- 8533805
TI  - Uniparental disomy in congenital disorders: a prospective study.
AB  - Whole chromosome uniparental disomy (UPD) for several different chromosomes has
      been described in individuals with phenotypes that encompass a broad range of
      abnormalities. We prospectively searched for UPD in 25 cytogenetically normal
      individuals who had one or more of the following features: nonsyndromic multiple
      congenital anomalies, short stature, mental retardation, or dysmorphic findings.
      Using highly polymorphic microsatellite repeats, biparental inheritance of at
      least one locus on every chromosome was found in every individual and uniparental
      inheritance was not detected at any locus. If UPD does exist in this clinical
      setting, its frequency is less than 13.7% (95% confidence interval). Our data
      indicate that additional studies will be required to determine the true incidence
      of UPD in this population.

PMID- 8533806
TI  - Maternal uniparental disomy of chromosome 2 in a baby with trisomy 2 mosaicism in
      amniotic fluid culture.
AB  - We describe the first case of a baby with maternal uniparental disomy of
      chromosome 2. Growth failure, hypothyroidism, and hyaline membrane disease were
      present at birth, and the first year of life was complicated by bronchopulmonary
      dysplasia. At age 14 months, motor and intellectual development were normal, but
      growth remained below the 10th centile. The baby was investigated for uniparental
      disomy because trisomy 2 mosaicism had been detected in a second trimester
      amniocentesis. This is the first reported case in which amniotic fluid chromosome
      mosaicism has been associated with uniparental disomy. Implications for prenatal
      diagnosis are considered.

PMID- 8533807
TI  - Intestinal lymphangiectasia in a patient with Zellweger cerebrohepatorenal
      syndrome.
AB  - Zellweger cerebrohepatorenal syndrome (ZWCHRS) is an autosomal-recessive disease,
      characterized by the absence or profound deficiency of peroxisomes. We report a
      case of ZWCHRS with intestinal lymphangiectasia, observed as an autopsy finding.
      This combination is previously unreported.

PMID- 8533808
TI  - Acute intermittent porphyria: a single-base deletion and a nonsense mutation in
      the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme
      polypeptide.
AB  - Acute intermittent porphyria (AIP) is an autosomal-dominant inborn error of
      metabolism that results from the half-normal activity of the third enzyme in the
      heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an
      ecogenetic condition, since the life-threatening acute attacks are precipitated
      by various factors, including drugs, alcohol, fasting, and certain hormones.
      Biochemical diagnosis is problematic, and the identification of mutations in the
      HMB-synthase gene provides accurate detection of presymptomatic heterozygotes,
      permitting avoidance of the acute precipitating factors. By direct solid-phase
      sequencing, two mutations causing AIP were identified, an adenine deletion at
      position 629 in exon 11(629delA), which alters the reading frame and predicts
      premature truncation of the enzyme protein after amino acid 255, and a nonsense
      mutation in exon 12 (R225X). These mutations were confirmed by either restriction
      enzyme analysis or family studies of symptomatic patients, permitting accurate
      presymptomatic diagnosis of affected relatives.

PMID- 8533809
TI  - Radio-ulnar synostosis, short stature, microcephaly, scoliosis, and mental
      retardation.
AB  - We report on a 9-year-old boy with radio-ulnar synostosis, short stature,
      microcephaly, scoliosis, and mental retardation. We propose that he has a new
      syndrome.

PMID- 8533810
TI  - Incidence and mortality rates of cystic fibrosis in Japan, 1969-1992.
AB  - The incidence rate and the death rate of cystic fibrosis (CF) in Japan were
      analyzed using Japanese Vital Statistics data for the period 1969-1992. The
      incidence rate was 3.1 per million live births during the period 1969-1980, where
      the rate was 1.5 times higher in rural than urban areas. The proportion of deaths
      from CF under 5 years old was 82% and under 20 years old was 94%. Overall death
      rates of CF per million population under 20 years of age were 0.15 for males and
      0.10 for females, the difference being significant; the death rate was also
      significantly higher in males (2.2 per million) than females (1.3) in the first
      year of life. The death rate decreased from the period 1969-1973 to the period
      1989-1992 for males. There were geographical variations in the incidence and the
      death rates among nine districts. These rates of CF were observed with the
      highest being in Hokkaido and the lowest in Okinawa. The death rate from CF was
      negatively correlated with the average temperature. The death rate was higher in
      rural than in urban areas during the period 1969-1985. The mean age at death from
      CF was 3 years for both sexes during the period 1969-1985, the value has been
      increased since 1979.

PMID- 8533811
TI  - Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders.
AB  - Marfan syndrome (MFS), a multisystem autosomal-dominant disorder, is
      characterized by mutations of the fibrillin-1 (FBN1) gene and by abnormal
      patterns of synthesis, secretion, and matrix deposition of the fibrillin protein.
      To determine the sensitivity and specificity of fibrillin protein abnormalities
      in the diagnosis of MFS, we studied dermal fibroblasts from 57 patients with
      classical MFS, 15 with equivocal MFS, 8 with single-organ manifestations, and 16
      with other connective tissue disorders including homocystinuria and Ehlers-Danlos
      syndrome. Abnormal fibrillin metabolism was identified in 70 samples that were
      classified into four different groups based on quantitation of fibrillin
      synthesis and matrix deposition. Significant correlations were found for
      phenotypic features including arachnodactyly, striae distensae, cardiovascular
      manifestations, and fibrillin groups II and IV, which included 70% of the MFS
      patients. In addition, these two groups were associated with shortened "event
      free" survival and more severe cardiovascular complications than groups I and
      III. The latter included most of the equivocal MFS/single manifestation patients
      with fibrillin abnormalities. Our results indicate that fibrillin defects at the
      protein level per se are not specific for MFS, but that the drastically reduced
      fibrillin deposition, caused by a dominant-negative effect of abnormal fibrillin
      molecules in individuals defined as groups II and IV, is of prognostic and
      possibly diagnostic significance.

PMID- 8533812
TI  - Characterization of genetic deletions in Becker muscular dystrophy using
      monoclonal antibodies against a deletion-prone region of dystrophin.
AB  - We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region
      of the dystrophin protein corresponding to a deletion-prone region of the
      Duchenne muscular dystrophy gene (exons 45-50). We show that immuno
      histochemistry or Western blotting with these "exon-specific" mAbs can provide a
      valuable addition to Southern blotting or PCR methods for the accurate
      identification of genetic deletions in Becker muscular dystrophy patients. The
      antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6),
      exon 47 (1), exons 47/48 (4), exons 48-50 (6), and exon 50 (1). PCR amplification
      of single exons or groups of exons was used both to produce specific dystrophin
      immunogens and to map the mAbs obtained. PCR-mediated mutagenesis was also used
      to identify regions of dystrophin important for mAb binding. Because the mAbs can
      be used to characterize the dystrophin produced by individual muscle fibres, they
      will also be useful for studying "revertant" fibres in Duchenne muscle and for
      monitoring the results of myoblast therapy trials in MD patients with deletions
      in this region of the dystrophin gene.

PMID- 8533813
TI  - Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980-1990.
      EUROCAT Working Group.
AB  - A total of 732 cases of omphalocele and 274 cases of gastroschisis was registered
      in 21 regional registers in Europe (EUROCAT registers) during the period 1980
      1990. The total prevalence rates were 2.52 per 10,000 for omphalocele and 0.94
      per 10,000 for gastroschisis. There was significant heterogeneity in total
      prevalence rates among regions for omphalocele. Consistently higher than average
      total prevalence rates of omphalocele were found in the five centers of the
      British Isles. This was in large part linked to the association between
      omphalocele and neural tube defects. A significant female excess among the cases
      of omphalocele associated with neural tube defects, in comparison with an
      insignificant male excess for other cases of omphalocele, was observed.
      Geographical differences in the total prevalence of gastroschisis are partly
      explained by differences in maternal age distributions in the populations
      surveyed. Omphalocele was an isolated malformation in 46% of cases; gastroschisis
      was isolated in 79% of cases. The average birthweight and gestational age of both
      isolated and multiply malformed cases of both omphalocele and gastroschisis were
      low, especially for multiply malformed cases, and to a greater extent for
      isolated gastroschisis than for isolated omphalocele. Prenatal diagnosis leading
      to termination of pregnancy was reported in 33.2% of omphalocele and in 26.5% of
      gastroschisis cases, demonstrating the considerable impact of current prenatal
      screening programs. On the basis of clinical manifestations, epidemiologic
      characteristics, and the presence and type of additional malformations,
      omphalocele and gastroschisis can be considered heterogeneous conditions.

PMID- 8533814
TI  - Clinical variability in neonatal progeroid syndrome.

PMID- 8533815
TI  - Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A.

PMID- 8533816
TI  - Melorheostosis and somatic mosaicism.

PMID- 8533817
TI  - Genetic mapping of the cleidocranial dysplasia (CCD) locus on chromosome band
      6p21 to include a microdeletion.
AB  - Cleidocranial dysplasia (CCD) is a generalized skeletal dysplasia with autosomal
      dominant inheritance. Recently, the CCD disease locus was localized to 23
      [Mundlos et al., 1995] and 17 cM regions [Feldman et al., 1995], of chromosome
      band 6p21 by linkage studies of seven affected families. Of note, the 23 cM
      region contained a microdeletion detected in one family at D6S459, an interval
      that was excluded in the 17 cM overlapping region. Here, linkage of CCD to 6p21
      was independently confirmed with a maximal two-point LOD score of Z = 5.12 with
      marker D6S452 at theta = 0.00. Recombinant events in two affected individuals
      defined a CCD region of 7 cM from D6S465 to D6S282, which overlapped with the CCD
      region containing the microdeletion but did not overlap with the 17 cM critical
      region from D6S282 to D6S291. These results suggest the refined localization of
      the CCD region to 6 cM spanning markers D6S438 to D6S282, thereby reviving the
      possibility that the CCD gene lies within the microdeletion at D6S459.

PMID- 8533818
TI  - Duchenne muscular dystrophy and idiopathic hyperCKemia segregating in a family.
AB  - A 7-month-old boy with gross motor delay and failure to thrive presented with
      rhabdomyolysis following an acute asthmatic episode. During hospitalization an
      electrocardiographic conversion to a Wolff-Parkinson-White type 1 (WPW) pattern
      took place. Duchenne muscular dystrophy (DMD) was suspected based on elevated
      creatine kinase (CK) serum levels, muscle biopsy, and family history. The
      diagnosis was confirmed by molecular analysis, which documented a deletion
      corresponding to cDNA probe 1-2a in the dystrophin gene, in the propositus and in
      an affected male cousin of his mother. "Idiopathic" hyperCKemia was found in the
      propositus, his father, and 5 of his relatives. We suggest that the unusually
      early and severe manifestations of DMD in this patient may be related to the
      coincidental inheritance of the maternal DMD gene and of a paternal gene, causing
      hyperCKemia.

PMID- 8533819
TI  - Syndrome of arachnodactyly, disturbance of cranial ossification, protruding eyes,
      feeding difficulties, and mental retardation.
AB  - We have evaluated an infant with a striking combination of craniofacial
      anomalies, arachnodactyly, and severe developmental failure. She died at the age
      of 5 months during a recurrent apneic episode. She also had protruding eyes,
      downward slant of palpebral fissures, short upturned nose, midface hypoplasia,
      micrognathia, extreme under-development of the epiglottis, and severe feeding
      difficulties. The patient closely resembled four other previously reported
      patients. It is suggested that these five patients represent the same
      malformation syndrome, a well-recognizable separate entity. Our patient also had
      a pericentric inversion of chromosome 10; a possible association of this with the
      phenotype cannot be excluded.

PMID- 8533820
TI  - Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does
      not detect recurrence.
AB  - Geleophysic dysplasia is characterized by short stature with short limbs and
      brachydactyly, a "happy" facial appearance, and joint contractures. Infiltration
      of heart valves and liver with a mucopolysaccharide-like substance has been
      demonstrated in some patients. A metabolic pathogenesis is suspected, but has not
      yet been identified. We report on 3 boys with the condition, 2 of whom are
      brothers. Serial ultrasound scans were performed on 2 of the cases during
      pregnancy, but short limbs did not become obvious until after 28 weeks of
      gestation, making it an uninformative procedure for prenatal diagnosis.

PMID- 8533821
TI  - Multi-site neural tube closure in humans and maternal folate supplementation.
AB  - A group of 13 individuals with neural tube defects (NTD) despite maternal
      periconceptional folate supplementation was examined to determine precisely which
      closure sites along the neural tube had failed during embryogenesis. All the
      common forms of NTD, and thus all the usual closure sites, were represented. This
      suggests that folate deficiency does not act specifically on one region of the
      neural tube; rather, it may be more generally involved in the cause of human NTD.

PMID- 8533822
TI  - Hereditary spherocytic anemia with deletion of the short arm of chromosome 8.
AB  - We describe a 30-month-old boy with multiple anomalies and mental retardation
      with hereditary spherocytic anemia. His karyotype was 46,XY,del(8)(p11.23p21.1).
      Genes for ankyrin and glutathione reductase (GSR) were localized to chromosome
      areas 8p11.2 and 8p21.1, respectively. Six patients with spherocytic anemia and
      interstitial deletion of 8p- have been reported. In these patients, severe mental
      retardation and multiple anomalies are common findings. This is a new contiguous
      gene syndrome. Lux et al. [1990: Nature 345:736-739] established that ankyrin
      deficiency and associated deficiencies of spectrin and protein 4.2 were
      responsible for spherocytosis in this syndrome. We reviewed the manifestations of
      this syndrome. Patients with spherocytic anemia and multiple congenital anomalies
      should be investigated by high-resolution chromosomal means to differentiate this
      syndrome.

PMID- 8533823
TI  - Clinical and cytogenetic findings in seven cases of inverted duplication of 8p
      with evidence of a telomeric deletion using fluorescence in situ hybridization.
AB  - We report on the clinical and cytogenetic findings in 7 cases of inverted
      duplication of region 8p11.2p23. The phenotype of inv dup (8p) compiled from this
      series and the literature (N = 29) consists of severe mental retardation (100%),
      minor facial alterations (97%), agenesis of the corpus callosum (80%), hypotonia
      (66%), orthopedic abnormalities (58%), scoliosis/kyphosis (40%), and congenital
      heart defect (26%). A telomeric deletion of region 8p23.3-pter was confirmed in 3
      of our cases studied using fluorescent in situ hybridization with a telomeric
      probe for 8p. Thus, these karyotypes are inv dup del(8) (qter-->p23.1::p23.1-
      >p11.2:). Our findings suggest that most cases of inv dup(8p) probably have a
      telomeric deletion.

PMID- 8533824
TI  - Duplication/deletion of chromosome 8p.

PMID- 8533825
TI  - Prenatal exposure to phenytoin, facial development, and a possible role for
      vitamin K.
AB  - Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were
      prenatally exposed to phenytoin (usually in combination with other
      anticonvulsants), were identified retrospectively. In addition to their facial
      anomalies, 6 of the patients were radiographed neonatally and showed punctate
      calcification, characteristic of chondrodysplasia punctata. Evidence is presented
      that the facial abnormalities seen in these children are due to anticonvulsant
      induced vitamin K deficiency, causing abnormal development of the cartilaginous
      nasal septum. We propose that early vitamin K supplementation of at-risk
      pregnancies may prevent the development of maxillonasal hypoplasia, which in some
      patients is severely disfiguring and causes great emotional distress. Correction
      of this facial defect requires surgical and dental treatment over a long period
      of time.

PMID- 8533826
TI  - Galloway-Mowat syndrome in Taiwan.
AB  - We report on two Chinese female infants with multiple congenital anomalies:
      microcephaly, apparent porencephaly or encephalomalacia, developmental delay,
      minor facial anomalies, and contractural arachnodactyly. In the first patient,
      focal glomerulosclerosis was diagnosed histologically by percutaneous renal
      biopsy due to proteinuria with hematuria. Congenital hypothyroidism presenting
      with markedly low T3 and T4 was also noted. She died at age 5 months. The second
      patient had a very similar condition but less severe brain and kidney
      malformations. A variant of Galloway-Mowat syndrome is suspected.

PMID- 8533827
TI  - Growth in stature in fragile X families: a mixed longitudinal study.
AB  - The effect of fragile X on growth in stature was estimated in individuals aged 5
      20 years from 50 fragile X families. The multivariate normal model for pedigree
      analysis was applied to the mixed longitudinal data, which varied with regard to
      intervals between the measurements and their number in individual subjects,
      totalling 349 measurement data points from fragile X families, and 292 data
      points from unrelated normal subjects. The results of genetic and regression
      analysis showed that, in fragile X boys and girls, total pubertal height gain is
      impaired, whereas the rate of growth during the preadolescent period is
      increased, compared with the growth rate of nonfragile X subjects. Moreover, the
      growth parameters in fragile X males were found to be correlated with the size of
      CGG trinucleotide expansion. The hypothesis of premature activation of the
      hypothalamo-pituitary gonadal axis is postulated as the cause of growth
      impairment in fragile X boys and girls, which should be verified by data on the
      timing of pubertal stages, hormone levels, and bone maturation.

PMID- 8533828
TI  - GAPO syndrome: report on the first case in Japan.
AB  - We studied a 3.5-year-old Japanese boy with growth retardation, alopecia,
      pseudoanodontia, and bilateral papilledema. He was born of nonconsanguineous
      parents, but his paternal grandparents were related. From his characteristic
      physical manifestations, we diagnosed him as the first known case of GAPO
      syndrome in Japan and perhaps in the Mongoloid race. Our case had prominent
      dilatation of scalp veins and an audible intracranial bruit. Cranial angiography
      documented a narrowing of the sigmoid sinuses, with no flow to either jugular
      vein. We discuss here the relationships between optic atrophy and intracranial
      vascular changes in this syndrome.

PMID- 8533829
TI  - Recurrent lambdoid synostosis within two families.
AB  - We report on 2 families with multiple members who have proven or suspected
      lambdoid craniosynostosis. In one family the lambdoid suture was unilaterally
      involved in one sib, and bilaterally in the other. In the second family the
      propositus had unilateral lambdoid synostosis and his twin sisters each had
      bilateral lambdoid synostosis. Both families had another distant relative, a
      maternal grandmother in the first and paternal uncle in the second, who were also
      reported to have posterior plagiocephaly. We report these families as evidence
      for genetic transmission of a craniosynostotic trait which has only been rarely
      reported previously.

PMID- 8533830
TI  - Missense mutation of the beta-cardiac myosin heavy-chain gene in hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or
      as a sporadic disease without familial involvement. We describe a missense
      mutation of the beta-cardiac myosin heavy chain (MHC) gene, a G to T transversion
      (741 Gly-->Trp) identified by direct sequencing of exon 20 in four individuals
      affected with familial hypertrophic cardiomyopathy. Three individuals with
      sporadic hypertrophic cardiomyopathy, whose parents are clinically and
      genetically unaffected, had sequence variations of exon 34 of the alpha-cardiac
      MHC gene (a C to T transversion, 1658 Asp-->Asp, resulting in FokI site
      polymorphism), of intron 33 of the alpha-cardiac MHC gene (a G to A and an A to T
      transversion), and also of intron 14 of the beta-cardiac MHC gene (a C to T
      transversion in a patient with Noonan syndrome). Including our case, 30 missense
      mutations of the beta-cardiac MHC gene in 49 families have been reported thus far
      worldwide. Almost all are located in the region of the gene coding for the
      globular head of the molecule, and only one mutation was found in both Caucasian
      and Japanese families. Missense mutations of the beta-cardiac MHC gene in
      hypertrophic cardiomyopathy may therefore differ according to race.

PMID- 8533831
TI  - Absence of lambda immunoglobulin sequences on the supernumerary chromosome of the
      "cat eye" syndrome.
AB  - The supernumerary bisatellited chromosome causing the "cat eye" syndrome (CES) is
      of chromosome 22 origin and consists of an inverted duplication of the 22pter-
      >22q11.2 region. To determine the extent of involvement of band q11.2 on the
      bisatellited chromosome, copy number assessment of sequences homologous to cloned
      lambda immunoglobulin (lambda Ig) gene region probes was carried out on DNA from
      individuals with CES using densitometric analysis of Southern blots. None of the
      10 lambda Ig sequences studied was found in increased copy number in DNA from any
      of the 10 CES individuals tested, indicating that these sequences are not present
      on the supernumerary chromosome. The breakpoints involved in the generation of
      the bisatellited supernumerary chromosome associated with CES are therefore
      proximal to the lambda Ig gene region.

PMID- 8533832
TI  - Skeletal abnormalities in Rett syndrome: increasing evidence for dysmorphogenetic
      defects.
AB  - The presence of metatarsal and metacarpal abnormalities in some individuals has
      raised the possibility that Rett syndrome is, in fact, a multiple congenital
      abnormalities/mental retardation (MCA/MR) syndrome. We have conducted
      radiological examination of 17 cases of Rett syndrome in Western Australia. Short
      fourth and/or fifth metatarsals were identified in 65% of cases and short fourth
      and/or fifth metacarpals in 57%. Metatarsal (P = 0.045) and metacarpal (P =
      0.006) shortness were significantly more common in girls 14 years or older.
      Negative ulnar variance (found in 79% of cases) appeared to be independent of
      age. Reduced bone density in the hands was found in 86% of cases. A nationwide
      study using the Australian Rett Syndrome Database is planned to follow up these
      findings and compare them with findings from a control group. The confirmation of
      these abnormalities in a high proportion of cases may provide morphologic markers
      to assist in the diagnosis of Rett syndrome and perhaps provide a further avenue
      of research into the pathogenesis of this disorder.

PMID- 8533833
TI  - Smith-Magenis syndrome deletion: a case with equivocal cytogenetic findings
      resolved by fluorescence in situ hybridization.
AB  - The availability of markers for the 17p11.2 region has enabled the diagnosis of
      Smith-Magenis syndrome (SMS) by fluorescence in situ hybridization (FISH). SMS is
      typically associated with a discernible deletion of band 17p11.2 upon cytogenetic
      analysis at a resolution of 400-550 bands. We present a case that illustrates the
      importance of using FISH to confirm a cytogenetic diagnosis of del(17)(p11.2).
      Four independent cytogenetic analyses were performed with different conclusions.
      Results of low resolution analyses of amniocytes and peripheral blood lymphocytes
      were apparently normal, while high resolution analyses of peripheral blood
      samples in two laboratories indicated mosaicism for del(17)(p11.2). FISH clearly
      demonstrated a 17p deletion on one chromosome of all peripheral blood cells
      analyzed and ruled out mosaicism unambiguously. The deletion was undetectable by
      flow cytometric quantitation of chromosomal DNA content, suggesting that it is
      less than 2 Mb. We conclude that FISH should be used to detect the SMS deletion
      when routine chromosome analysis fails to detect it and to verify mosaicism.

PMID- 8533834
TI  - Elevated MSAFP levels and congenital heart defects: are there associations?

PMID- 8533835
TI  - Are the faciothoracoskeletal syndrome and the Guadalajara camptodactyly syndrome
      type I distinct entities?

PMID- 8533836
TI  - Syndrome of proximal interstitial deletion 4p15.

PMID- 8533837
TI  - Four new cases of inverted terminal duplication: a modified hypothesis of
      mechanism of origin.
AB  - We present 4 recently diagnosed cases of inverted tandem duplication with
      involvement of the respective terminal band. Based on these 4 cases and review of
      the literature, the term "inverted terminal duplication" is proposed to designate
      specifically the type of inverted tandem duplication which involves the terminal
      band. A modification of the previous hypothesis of mechanism of origin is
      advanced. It is speculated further that a telomeric deletion of a meiotic
      chromosome followed by a U-type reunion of the chromatids, considered to be the
      first steps of the proposed mechanism of origin, may not be a rare gonadal event.

PMID- 8533838
TI  - Absence of correlation between utrophin localization and quantity and the
      clinical severity in Duchenne/Becker dystrophies.
AB  - While present in the surface membrane of embryonic muscle fibers, in adult normal
      muscle fibers, utrophin is restricted to the motor endplate and cells of blood
      vessel walls. However, the observation that utrophin is maintained in the
      extrajunctional plasma membrane in Duchenne (DMD) and in mdx muscle fibers has
      led to the suggestion that excess utrophin might compensate for dystrophin
      deficiency in the Xp21 muscular dystrophies. In order to detect an inverse
      correlation of utrophin presence and clinical severity, we have assessed utrophin
      distribution and quantity in DMD and Becker (BMD) patients of different ages and
      stages of clinical severity. All patients showed a positive discontinuous
      immunolabeling of utrophin on the sarcolemma, staining equally small and large
      muscle fibers, indicating that immature characteristics are maintained in such
      fibers. On Western blot, utrophin bands with concentrations 2- to 10-fold greater
      than in normal controls were detected in all DMD/BMD patients. However, no
      negative correlation was found between the amount of utrophin and the severity of
      clinical course, implying that the detectable utrophin levels in these patients
      did not compensate for dystrophin deficiency. In a DMD patient with growth
      hormone (GH) deficiency and a BMD-like clinical course, utrophin levels were
      comparable to the other typical DMD cases, which reinforces the hypothesis that
      the observed increase in utrophin is apparently not responsible for a milder
      clinical course in some patients with Xp21 muscular dystrophies.

PMID- 8533839
TI  - Transient leukemia with trisomy 21: description of a case and review of the
      literature.
AB  - Transient myeloproliferative disease (TMD) is often associated with a trisomy 21
      cell line, but it is not always associated with clinical signs of Down syndrome.
      We report on a phenotypically normal newborn boy who presented with a high white
      blood cell count, undifferentiated blasts, and cutaneous leukemic infiltrates and
      compare this patient with the literature on TMD and trisomy 21. Chromosome
      analysis of bone marrow, and subsequently of skin fibroblasts, documented
      constitutional mosaicism for trisomy 21. A decrease in the frequency of blast
      cells paralleled a decrease in cells demonstrating trisomy 21 in hematopoietic
      tissues, and a complete clinical recovery was seen without the use of
      chemotherapy. Recognition of this transient form of congenital leukemia is
      important to prevent the unnecessary use of toxic chemotherapeutic agents in such
      patients.

PMID- 8533840
TI  - Impact of apolipoprotein E genotype variation on means, variances, and
      correlations of plasma lipid, lipoprotein, and apolipoprotein traits in
      octogenarians.
AB  - The impact of apolipoprotein (apo) E genotype variation on means, variances and
      correlations between plasma lipid traits was studied in male and female
      octogenarians. Females had significantly higher mean levels of all 10 of the
      measured plasma lipid traits than males. The subset of concomitants (i.e., age,
      height, weight, body mass index, glucose and uric acid) that made a statistically
      significant contribution to interindividual variability was different in males
      and females for every trait considered. Gender-specific associations between
      variation in apo E genotype and variation in particular measures of lipid
      metabolism, adjusted for concomitant variation, were observed: in females there
      were no statistically significant associations while in males the means of the
      three common apo E genotypes were significantly different for adjusted measures
      of total cholesterol, low density lipoprotein cholesterol and low density
      lipoprotein-apo B. The common apo E genotypes were heterogeneous with respect to
      intragenotypic variance for adjusted log-transformed triglyceride levels in
      females only. Finally, the three common apo E genotypes were heterogeneous with
      respect to the correlation between traits, adjusted for concomitant variation,
      and gender influenced the manner in which the genotypes differed for specific
      correlations. This study documents that variation in the apo E gene has a
      significant impact on means, variances and correlations of plasma lipid traits in
      octogenarians, but the effects are context-, that is gender- and age-, dependent.

PMID- 8533841
TI  - Sex, neural tube defects, and multisite closure of the human neural tube.
AB  - While neural tube defects (NTD) overall have a female sex bias, this does not
      apply to all sites along the neuraxis. The findings regarding sex and NTD in a
      series of midtrimester fetuses are reviewed, and then analysed in terms of the
      recent hypothesis that during embryogenesis of the human neural tube there are
      multiple closure sites, rather than a single zipping up process. Females more
      often than males tend to have craniorachischisis, spina bifida involving the
      thorax, the holoacrania form of anencephaly, anencephaly and cervical spina
      bifida and encephalocoeles, while males more often than females have spina bifida
      affecting the lower spine. Meroacrania occurs equally in both sexes. Other
      sources indicate that there is a male bias in frontoethmoidal encephalocoeles.
      Since sex seems to be a factor that is differentially associated with lack of
      closure of specific areas of the neural tube, it would seem to support the notion
      that there are multiple closure sites in the human neural tube. However, no
      association was found between a particular sex and either the type of NTD which
      have an isolated abnormality or those NTD associated with developmental
      abnormalities of other body systems.

PMID- 8533842
TI  - Use of decision analysis to evaluate patients' choices of diagnostic prenatal
      test.
AB  - Women with a family history of a chromosomal or genetic abnormality must weigh
      several factors in choosing between amniocentesis and chorionic villus sampling.
      We compared the prenatal test choices of three such women with those of decision
      analytic models that incorporated their preferences. Patient preferences were
      assessed using visual linear rating scales. Threshold analysis was used to
      determine preference ranges, and stochastic sensitivity analysis to provide
      confidence levels, for each choice of test. The test choices of patients and
      decision analytic models agreed in one case, and disagreed in two cases. In one
      of the latter two cases, stochastic and threshold analyses showed the
      disagreement to be slight; for small shifts in preference differences for first-
      vs. second-trimester diagnosis, or first- vs. second-trimester therapeutic
      abortion, patient and decision model would have agreed. In the other, stochastic
      analysis showed their differences to be large; there were no thresholds for early
      diagnosis, or for early therapeutic abortion, that would have led to agreement
      between patient and model. In the two cases in which patient and decision model
      agreed or slightly disagreed, the patients had made their own choice of prenatal
      test. In the case in which patient and decision model strongly disagreed, the
      patient's physician had shared in the choice of test. Decision analysis can be
      useful in analyzing prenatal test choices based on individual preferences for
      pregnancy outcomes. When choices of patients and decision models do not agree,
      examination of the locus of decision making (patient vs. physician) may help
      resolve apparent differences.

PMID- 8533843
TI  - "New" ectodermal dysplasia with mental retardation and syndactyly.
AB  - We describe a girl with an unusual form of ectodermal dysplasia. She was mildly
      mentally retarded, had normal height, weight, and head circumference, a large
      scalp defect, a peculiar face with large palpebral fissures, a broad nasal bridge
      and constantly open mouth, abnormally-modeled ears, syndactyly of fingers/toes,
      mild hypohidrosis, and severe onychogryposis. Her hair was short, abundant, and
      stiff, her eyebrows were sparse, and her skin was dry. Analysis of the literature
      showed that this type of association of ectodermal dysplasia and other defects
      has not been previously described.

PMID- 8533844
TI  - Craniomicromelic syndrome: a newly recognized lethal condition with
      craniosynostosis, distinct facial anomalies, short limbs, and intrauterine growth
      retardation.
AB  - We report on two sisters with an unusual form of craniosynostosis, protruding
      nasal spine, micrognathia, short limbs, lung hypoplasia, absent or hypoplastic
      gallbladder, short intestine with ileal distention, hypoplastic uterus, and
      intrauterine growth retardation. This combination of defects appears to be a
      newly recognized and probably autosomal recessive disorder.

PMID- 8533845
TI  - Juberg-Marsidi syndrome: report of an additional case.
AB  - We report on a 2-year-old boy with Juberg-Marsidi syndrome. He has mental
      retardation, short stature, micropenis, cryptorchidism, and minor facial
      abnormalities. His Leydig cells responded to the administration of human
      chorionic gonadotropin and there were positive responses of LH and FSH to the
      administration of LH-RH. He showed normal weight gain and head circumference
      which have not been described previously. The association of Juberg-Marsidi
      syndrome with HbH disease was ruled out in the propositus.

PMID- 8533846
TI  - Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic
      fibrosis mutation 3849 + 10kbC > T: significance for geneticists.
AB  - We describe patients inheriting cystic fibrosis (CF) mutation 3849 + 10kb > T as
      homozygotes or compound heterozygotes. Three unrelated homozygotes for this
      mutation were all pancreatic-sufficient and sweat test-negative or inconclusive.
      Among the compound heterozygotes, both pancreatic sufficiency and insufficiency,
      as well as positive and negative/inconclusive sweat test results are reported,
      expanding the range of clinical expression associated with inheritance of this
      mutation. 3849 + 10kbC > T is one of several CF mutations that can result in
      atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has
      implications for recurrence risk and prognosis counseling of the families of
      affected individuals, and possibly for CF carrier screening in the general
      population.

PMID- 8533847
TI  - Maternal origin of extra haploid set of chromosomes in third trimester triploid
      fetuses.
AB  - Twenty-six highly polymorphic markers were used to determine the origin of the
      extra haploid chromosome set in 6 triploid fetuses of type II phenotype. All had
      reached the third trimester of pregnancy. The extra set was maternal in origin in
      all cases, supporting previous research indicating longer in utero survival of
      maternally-derived triploid fetuses. These findings provide evidence for an
      instance of genomic imprinting in humans.

PMID- 8533848
TI  - Phenotypic manifestations of branchio-oto-renal syndrome.
AB  - Branchiootorenal (BOR) syndrome is a variable, autosomal-dominant disorder of the
      first and second embryonic branchial arches, kidneys, and urinary tract. We
      describe the phenotype in 45 individuals, highlighting differences and
      similarities reported in other studies. Characteristic temporal bone findings
      include cochlear hypoplasia (4/5 of normal size with only 2 turns), dilation of
      the vestibular aqueduct, bulbous internal auditory canals, deep posterior fossae,
      and acutely-angled promontories.

PMID- 8533849
TI  - Enamel hypoplasia, bilateral cataracts, and aqueductal stenosis: a new syndrome?
AB  - We report on a 12-year-old girl who presented with generalized enamel hypoplasia,
      cataracts, and enlargement of the cerebral ventricles secondary to aqueductal
      stenosis. Previously described syndromes of enamel defects with or without
      cataracts were excluded on the basis of clinical criteria and appearance of the
      dentition. Metabolic conditions which could have caused cataracts were excluded
      clinically and by biochemical tests. The combination of signs in this patient may
      represent a new syndrome.

PMID- 8533850
TI  - Increased first trimester nuchal translucency as a prenatal manifestation of
      Smith-Lemli-Opitz syndrome.
AB  - Routine ultrasound examination at 11 weeks of gestation in a woman with no family
      history of genetic disease demonstrated increased accumulation of fluid in the
      fetal nuchal region. In view of the association of this defect with chromosomal
      abnormalities, fetal karyotyping was performed by chorion villus sampling and
      this demonstrated a normal 46,XY karyotype. Subsequent scans showed resolution of
      the nuchal fluid, and at the 20-week scan the fetal genitalia appeared to be
      female. Fetal blood sampling confirmed a normal male karyotype and fetoscopy
      confirmed the presence of female external genitalia. The parents elected to
      terminate the pregnancy, and postmortem findings were indicative of Smith-Lemli
      Opitz syndrome. This was confirmed by the finding of increased levels of 7
      dehydrocholesterol in cultured skin fibroblasts.

PMID- 8533851
TI  - Nosology of omodysplasia.

PMID- 8533852
TI  - Views of euthanasia for sufferers of genetic disease: comments on the Felon case.

PMID- 8533853
TI  - Murder of son with a genital malformation.

PMID- 8533854
TI  - Mutation analysis of Australasian Gaucher disease patients.

PMID- 8533855
TI  - Neurovascular anomaly in a patient with VATER association: coincident or
      syndromal?

PMID- 8533856
TI  - Annular pancreas in two sisters.

PMID- 8533857
TI  - Differences between the Hoyeraal-Hreidarsson syndrome and an autosomal recessive
      congenital intrauterine infection-like syndrome.

PMID- 8533858
TI  - Case of paracentric inversion 19p.

PMID- 8533859
TI  - Detection of a subtle rearrangement of chromosome 22 using molecular techniques.
AB  - Conventional cytogenetics is a useful clinical tool that has a lower limit of
      sensitivity of 2-5 Mb for detection of duplications or deletions. Because the
      threshold of clinically significant aneusomy is below this range, there is a need
      for approaches to improve the sensitivity of the detection of aneusomy. We have
      implemented a system of screening for subtle unbalanced translocations in
      children with multiple congenital anomalies of unknown cause. Our approach uses
      subtelomeric microsatellite markers to detect small areas of segmental aneusomy
      due to unbalanced translocations. Herein we report a patient with severe multiple
      congenital anomalies and a normal karyotype who was diagnosed by this approach.
      Microsatellite markers from 41 telomeres were analyzed and were normal with the
      exception of those on distal chromosome 22. Further analysis with additional
      microsatellites and fluorescent in situ hybridization confirmed duplication of
      22q13.2-qter. We conclude that microsatellite screening can detect subtle
      unbalanced translocations in children with severe anomalies.

PMID- 8533860
TI  - The ambiguity of transference.
AB  - This paper has attempted to find relationships between different psychoanalytic
      schools, as well as between seemingly disparate views in theoretical and
      technical debates, along the essentially ambiguous concept of transference.
      Seeing transference as a condensation as well as a displacement, as recommended
      by Jordan (1992), has greatly facilitated this task by revealing an ongoing
      dialectical counterpoint of psychoanalytic dialogue. A sitting duck, the analyst
      conjures up a demand for recognition by the patient that is made more transparent
      in its contradiction by the analyst's quality of a decoy. As the scarecrow comes
      to life, the patient finds out that his demand cannot be fulfilled because
      ultimately it does not fit as it does not truly come from him. As it becomes
      clear that it does not come from the analyst either, the analyst as proxy gives
      all the clues as to the true source of desire. The many issues raised by Freud's
      monumental discovery are far from solved, and they surely will continue to
      inspire a continuing scientific dialogue. The issue of recognition in the
      Hegelian sense is suggested as a potentially fruitful common denominator of the
      transferential quest, to be further explored.

PMID- 8533861
TI  - Analytic asymmetries and their discontents.

PMID- 8533862
TI  - Postmodernism--feminism and the deconstruction of the feminine: Kristeva and
      Irigaray.

PMID- 8533863
TI  - Adolescent character formation and psychoanalytic theory.
AB  - The foremost implication of the Freudian theories of adolescence has been that
      the analyst enters into an alliance with the patient's developmental process.
      During sessions, stock is routinely taken of the adolescent patient's defenses
      and drive fixations. The interpersonal and object relations theories of
      adolescents' character formation varied with each other and also with the
      assumptions of classical Freudian metapsychology. Yet, Sullivan, Fairbairn, and
      Winnicott all stressed relatedness in character formation. They each urged that
      the attitudes of the actual person in significant relationships, as well as the
      internal representations of the self and the object, shaped the character
      tendencies of the child or adolescent. Sullivan was very outspoken about his
      belief that there could be no uniformly valid theory of character, because people
      are unique. However, for Sullivan, the needs for the validation of self-worth,
      and for freedom from anxiety, were universal stimuli for the increasing
      organization of character trends. In both interpersonal theory and object
      relations theories, dissociative processes were of paramount importance as
      defensive operations. Dissociation by the adolescent resulted in further
      instances of ego splitting (for Fairbairn), of the bad me (for Sullivan), and of
      the false self (for Winnicott). Fairbairn, and to some extent Winnicott, used the
      language of classical Freudian theory in order to shape an object relations
      theory of adolescent development. In spite of their theoretical differences,
      Sullivan, Fairbairn, and Winnicott spoke with a singular voice in dismissing the
      exclusive significance of libidinal fixations in character consolidation. I now
      wish to review Freud's case of Dora as an addendum to this short critical
      appraisal. The analysis of Dora readily lends itself to a discussion of the
      confluence of the psychoanalytical models' clinical theories. Dora's unfortunate
      experience in treatment offered a compelling example of the precariousness of
      adolescents' adjustment in the midst of developmental and family turmoil.

PMID- 8533864
TI  - Peter Shaffer's Amadeus as a further expression of twinship conflict.
AB  - In Peter Shaffer's Amadeus, which has much of a thematic and symbolic nature in
      common with its forerunners, Equus and The Royal Hunt of the Sun, stemming
      genetically from the unique sibling rivalry of twinship, there is more pronounced
      emphasis on the influence of envy and vengeance on human behavior than in the
      other two plays. It is postulated that the success of Equus and its implications
      pertinent to the competitive aspect of the relationship with his twin brother
      stirred appreciable intrapsychic turmoil in Shaffer and was a decisive motivating
      factor in his writing of Amadeus.

PMID- 8533865
TI  - Conflict and deficit: toward an integrative vision of the self.

PMID- 8533866
TI  - More on "Jacob Freud and Talmudic teachings".

PMID- 8533867
TI  - [Analysis of heart rate variability. Background, method, and possible use in
      anesthesia].
AB  - BACKGROUND AND METHODS. Small, periodic fluctuations in heart rate are well known
      to physicians, the respiratory sinus arrhythmia (RSA) being the most easily
      detectable form of this heart rate variability (HRV). Since it is caused by
      changing activity of the autonomic nervous system (ANS) controlling heart rate,
      HRV is investigated to gain information on the functional states of the ANS.
      Recent developments have led to computer-aided processing of EKG signals based on
      time and frequency domain methods--the latter using power spectral analysis by
      fast Fourier or autoregressive algorithms--to exactly describe and quantify HRV.
      Three major regions in the frequency spectrum between 0.03 and 0.5 Hz (the
      suitable range for shortterm recordings) have been established: (1) a region
      around the respiratory rate, usually between 0.2 and 0.35 Hz, called high
      frequency (HF), (2) a region around 0.1 Hz attributed to vasomotor activity
      feedback, called low (or mid-) frequency (LF), (3) a peak around 0.04-0.05 Hz
      correlated to thermoregulation, called very low (or low)frequency (VLF). Power
      spectral density of HRV is now commonly accepted as a measure of autonomic
      cardiovascular control activity. By studies on vagal or sympathetic blockade, the
      HF (or RSA) region has been attributed solely to vagal activity, while both parts
      of the ANS may contribute to the other two, with, however, the vagal part
      predominating the resting, healthy individuals. CLINICAL
      APPLICATIONS/ANAESTHESIA. Thus, spectral analysis of HRV provides a measure for
      quantifying sympatho-vagal balance in its physiological range. Additionally,
      reduction of HRV along with cardiovascular disease, including hypertension,
      myocardial infarction, heart failure and sudden cardiac death, as well as with
      autonomic dysregulation, has been reported. Since is also a striking reduction
      produced by most anaesthetic agents, RSA and HRV are investigated as measures of
      anaesthetic depth. There are contradictory data on the influence of ventilation,
      medication, and co-existing disease on the spectrum, and thus validation of the
      method is still to be achieved. It has, however, been proven useful in some
      studies as a parameter for risk assessment of perioperative or post-infarction
      cardiovascular complications.

PMID- 8533868
TI  - [Qualitative comparison of modified neurolept-, balanced and intravenous
      anesthesia. 2. Results of a clinical study, 1992].
AB  - The safety and tolerance of neuroleptanaesthesia (NLA), balanced anaesthesia
      (BAL), and intravenous anaesthesia with propofol (IVA) were analysed for the
      first time in a prospective, randomised clinical trial. METHODS. In all, 1318
      surgical patients received either NLA, BAL, or IVA. Patients who had regional
      anaesthesia, were aged under 18 years, or were non-cooperative or vitally
      threatened (ASA class i.v. to V) did not participate in the study. Premedication
      and anaesthetic course were set up at a standard of 30% oxygen and 70% nitrous
      oxide. Incidents, events, and complications due to anaesthesia were obtained (IEC
      key of the German Society of Anaesthesia and Critical Care Medicine, DGAI).
      Furthermore, postanaesthetic alertness based on specific recovery tests and the
      quality of anaesthesia from the patient's viewpoint, rated by patient
      questionnaires from the DGAI were evaluated. All parameters were calculated and
      checked for statistical significance using the chi-square test. RESULTS AND
      DISCUSSION. The groups were broadly comparable with respect to age (P = 0.91),
      ASA class (P = 0.42), preoperative blood pressure (P = 0.36), and length of
      anaesthesia (P = 0.82). The anaesthesia, which averaged 103 min, comprised the
      following regimens: (1) NLA: 7.1 mg droperidol and 0.008 mg/kg body weight
      fentanyl, (2) IVA: 493.4 mg propofol and 0.004 mg/kg body weight fentanyl, and
      (3) BAL: 2.6 mg droperidol and 0.004 mg/kg body weight fentanyl with 0.4 vol.%
      isoflurane. With respect to anaesthetic risk, the following reactions were
      observed: the use of NLA led to a high incidence of tachycardia (P = 0.001),
      arrhythmias (P = 0.05), and hypertensive reactions (P = 0.001), whereas in the
      IVA group only hypotension (P = 0.0001) occurred. However, after the use of BAL
      none of the aforementioned complications were detectable to any considerable
      degree. Similarly, patients who had cardiac disease showed greater IEC changes
      after the use of NLA than after BAL or IVA (P = 0.02) (Tables 1 and 2). The heart
      rates and blood pressures during BAL and IVA were extremely stable, and
      therefore, vasoactive therapy was required considerably less in comparison to NLA
      (P = 0.001) (Table 4). Recovery after the use of IVA was strikingly rapid: the
      patient's responsiveness, orientation, and ability to concentrate was
      significantly better than after the other anaesthetic regimen (P = 0.01) (Table
      5). With regard to the typical discomforts after anaesthesia, IVA was highly
      superior to BAL and NLA: nausea (P = 0.0003) and retching (P = 0.03) hardly ever
      occurred (Table 6). Due to the tolerable manner of waking up and rapid return of
      orientation and the ability to concentrate, IVA was highly favoured by the
      patients (P = < 0.01) (Table 7). CONCLUSION. The present results show clear
      clinical advantages of BAL and IVA in contrast to neuroleptanaesthesia. Due to
      the very low incidence of side effects such as nausea and vomiting IVA was highly
      recommended by the patients, at least in part because of the rapid recovery time.

PMID- 8533869
TI  - [Does controlled hypotension with nitroprusside affect platelet function?].
AB  - Induced hypotension is an accepted technique to reduce intraoperative blood loss
      and thereby ensures satisfactory operating conditions, especially in microscopic
      interventions. Sodium nitroprusside (NP), which is often used for induced
      hypotension, was reported to inhibit platelet aggregation in vitro. Impairment of
      platelet function implies a higher bleeding risk, which would make the use of NP
      for induced hypotension questionable. METHODS. With the approval of the local
      ethics committee, 30 patients scheduled for nasal septum operations were included
      in this randomised study. For induction of anaesthesia 2 mg vecuronium, 0.1 mg
      fentanyl, 0.2 mg/kg etomidate, and 1 mg/kg succinylcholine were used. After
      tracheal intubation the patients inhaled 1.0-1.5 vol.% isoflurane in a gas
      mixture containing 66% nitrous oxide in oxygen. Fifteen patients received an i.v.
      infusion of NP for 60 min. The concentrations chosen produced a decrease of mean
      arterial blood pressure to 50 mm Hg. Blood samples were taken before induction of
      anaesthesia; after induction of anaesthesia but before beginning of the
      operation; and 60 min after the beginning of the operation. This time-point
      coincided with the end of NP administration in the study group. The last blood
      sample was drawn the morning after the operation. Platelet function was
      determined in platelet-rich plasma by a turbidometric method after adding 22
      mumol/l epinephrine to induce aggregation. The spontaneous aggregation was
      measured in whole blood using impedance aggregometry. Data within one group were
      analysed using analysis of variance. Student's t-test for unpaired values served
      to compare data between the two groups. RESULTS. Biometric data in the two groups
      were comparable. The blood loss in the control group [265 (190-410) ml]
      significantly exceeded (P < 0.05) that in the hypotensive group [125 (75-210)
      ml]. No significant changes in platelet function were found throughout the study
      period in the patients treated with NP. In the control patients the epinephrine
      induced aggregation increased significantly from 53.1 +/- 5.3% before anaesthesia
      to 72.1 +/- 3.3% the morning after the intervention. The spontaneous aggregation
      showed a significant increase from 0.718 +/- 0.338 Ohm/h before anaesthesia to
      2.164 +/- 0.442 Ohm/h 60 min after the beginning of the operation. The value on
      the 1st postoperative day (2.266 +/- 0.448 Ohm/h) was also significantly higher
      than the basal value. CONCLUSIONS. In contradiction to in vitro studies using
      high concentrations of NP, we could not find a decrease in platelet aggregation
      due to hypotensive anaesthesia with this drug in vivo. In the control group a
      significant increase in platelet aggregation was observed, which was probably
      counteracted in the hypotensive patients by the interaction of NP with cyclic
      guanosine monophosphate (c-GMP). NP augments the intracellular concentration of c
      GMP, which is known to decrease platelet aggregation.

PMID- 8533870
TI  - [The determination of total protein is not a suitable diagnosis for the treatment
      of hypoalbuminemia in intensive care patients].
AB  - In clinical practice, the administration of supplementary albumin often depends
      on the measured plasma concentration of total protein (TPC). A TPC of less than 5
      g/dl is generally accepted as an indication for albumin therapy, assuming an
      albumin concentration of less than 2.5 g/dl. However, a physiological relation
      between TPC and albumin cannot be expected in critically ill patients, and thus,
      measurement of TPC may be misleading as an indicator for the use of albumin.
      Therefore, we investigated the sensitivity and specificity of TPC testing for
      diagnosing hypoalbuminaemia requiring treatment. METHODS. In this prospective
      study, 210 consecutive patients were included. Protein electrophoresis was
      performed three times a week; the second electrophoresis was selected for
      evaluation. Applied statistical analysis revealed the number of positive total
      protein tests indicating hypoalbuminaemia requiring treatment (sensitivity) and
      the number of negative with tolerable reduced albumin concentrations
      (specificity). RESULTS. Of the investigated patients, 27.6% had normal TPCs
      between 6.2 and 8.0 g/dl. In 81.9% of cases an albumin concentration below 3.5
      g/dl was found, while 43 patients had a concentration below 2.5 g/dl. The
      sensitivity and specificity of TPC measurement for the diagnosis of clinically
      relevant hypoalbuminaemia (albumin concentration < 2.5 g/dl) was calculated at
      different cutoff points for total protein. With a TPC of 6.0 g/dl, the
      sensitivity was 0.96 and the specificity 0.44. With a cutoff point of 5.0 g/dl,
      the sensitivity was reduced to 0.65 and specificity increased to 0.86. Finally,
      with a TPC of 4.0 g/dl sensitivity was 0.25 and specificity almost 1.
      CONCLUSIONS. Depending on the cutoff point for TPC, a relevant albumin
      requirement would frequently not be detected. In other cases, a need for albumin
      would be assumed from a reduced TPC even though the albumin concentration still
      exceeded 2.5 g/dl. Therefore, determination of TPC is not a suitable indicator of
      the need for albumin replacement. As a result, we suggest routine determination
      of albumin concentrations instead of TPC.

PMID- 8533871
TI  - [Cerebral monitoring with trancranial doppler-sonography and cerebrovenous
      oximetry during resuscitation].
AB  - This case report describes cerebral monitoring of intracranial haemodynamics
      using transcranial Doppler sonography (TCD) and jugular bulb oxygen saturation
      (SjO2) by fiberoptic jugular bulb oximetry during cardiac arrest following
      cardiac surgery involving cardiopulmonary bypass (CPB). CPB for aortic valve
      replacement and coronary artery bypass grafting was performed in a 63-year-old
      patient previously operated upon for heart disease. Mean blood flow velocity was
      measured in the middle cerebral artery using a bidirectional 2 MHz TCD system.
      SjO2 was measured using a fiberoptic thermodilution catheter placed in the right
      jugular bulb via the right internal jugular vein under radiographic control. At
      the end of the operation, low cardiac output syndrome and cardiac arrest
      occurred, which required reopening of the thorax and cardiopulmonary
      resuscitation (CPR) until CPB could be resumed. Following extrathoracic cardiac
      resuscitation, systolic "spikes", loss of the diastolic flow profile, and no
      increase in SjO2 were recorded by the monitors, indicating cerebral circulatory
      arrest. However, a normal flow profile with increasing diastolic portions and an
      increase in SjO2 to 52% were seen following optimisation of the open thorax
      cardiac resuscitation. This monitoring may be able to give information to
      optimise therapy during CPR to avoid ischaemic cerebral injury.

PMID- 8533872
TI  - [Intraoperative thrombosis of the inferior vena cava].
AB  - A pre-term infant weighing 900 g, gestational age 25 weeks, developed an acute
      abdomen. Intravenous lines had been inserted previously in the left (silastic
      catheter) and right (24 G cannula) saphenous veins in the neonatal intensive care
      unit. During surgical exploration, a perforation of the terminal ileum was found.
      The operation consisted in partial resection of the perforated ileum with an end
      to-end anastomosis and a double-lumen colostomy. Major blood loss during the
      procedure caused serious haemodynamic problems. Despite transfusion of
      erythrocyte (100 ml), thrombocytes (75 ml), and albumin (50 ml), the patient
      developed bradycardia and hypotension. Administration of atropine, adrenaline,
      and calcium i.v. had no effect. The operation could be finished only with
      extrathoracic resuscitation. When the drapes were removed, livid, swollen lower
      limbs raised the suspicion of an acute thrombosis of the inferior vena cava.
      After insertion of a 24 G i.v. cannula into a vein of the right upper arm, the
      circulation stabilised after rapid transfusion of 40 ml blood and 25 ml
      thrombocytes and resuscitation was successful. Paediatricians and
      anaesthesiologists must consider the risk of thrombosis of the vena cava. If
      venous lines in the lower limbs are not visible to the anaesthesiologist during
      the operation, venipuncture of veins of an upper limb is recommended before
      starting the surgical procedure. Due to the high incidence of vena cava
      thrombosis caused by central venous lines and the difficulty of peripheral
      venipuncture in pre-termintanty, a safe venous line should be inserted if
      necessary by pre-operative venesection.

PMID- 8533873
TI  - [The laryngeal mask airway in the difficult intubation. The results of a
      prospective study].
AB  - OBJECTIVE: The laryngeal mask airway (LMA) was prospectively used in patients who
      were difficult to intubate to evaluate whether it improves ventilation compared
      to a face mask, facilitates fibreoptic intubation, and how often blind intubation
      would be possible. METHODS: In a university hospital, 30 patients who were
      difficult to intubate (35 operative procedures) and 50 normal subjects were
      investigated; 23 patients had had radical resection of a facial tumor with
      irradiation at a previous time and 7 could not be intubated conventionally (grade
      3 and 4 visibility of the larynx according to Cormack [14]). Blind intubation was
      attempted with a bent bougie, a 6.0-mm uncuffed tube, or a straight bougie.
      RESULTS: Insertion of the LMA was possible in all except 1 patient with a mouth
      opening of 1 cm. Ventilation via the LMA was always excellent and, for tumor
      patients, superior to a face mask. In tumor patients, leak pressure was higher
      than in patients with normal cervical anatomy either with or without difficult
      intubation conditions (25.2 +/- 7.9, P < 0.05, vs. 20.8 +/- 4.4 vs. 20.6 +/- 4.9
      cmH2O; n.s.; Fig. 2). Fibreoptic intubation through the LMA was successful in all
      cases and easier than via a nasal or oral route. Blind intubation was successful
      in 22% of difficult to intubate patients and 19% of normals, mainly using a 6.0
      mm uncuffed endotracheal tube. Substitution of an uncuffed oral tube inserted via
      the LMA by a nasal endotrachel tube using a reinforced stomach tube is described
      (Fig. 4). CONCLUSION: The LMA improves ventilation, facilitates fibreoptic
      intubation, and offers the possibility for blind endotracheal intubation in
      difficult to intubate patients. Blind intubation though the LMA has to be
      practised extensively to have a high success rate. The LMA represents an
      additional aid for the anaesthetic management of patients who are difficult to
      intubate.

PMID- 8533874
TI  - [Principles of chronic pain therapy with opioids. Results of a Serturner workshop
      "Chronic Opioid Therapy"].

PMID- 8533875
TI  - [Occupational medicine and safety technology concerns for the permanent
      anesthetist].

PMID- 8533876
TI  - [Therapy with blood and blood products].

PMID- 8533877
TI  - Nonideal size-exclusion chromatography with zwitterions causes a pI-dependent
      elution of proteins from glycerol propylsilane-modified silica.
AB  - A potato homogenate containing proteins of similar molecular weights but varying
      pI values was separated by nonideal size-exclusion chromatography after attempts
      to resolve the proteins with common size-exclusion chromatography methods failed.
      The method used a zwitterion buffer to amplify electrostatic interactions between
      the proteins and the silica matrix. The proteins were sorted on the basis of pI
      in preference to molecular weight. Subsequent tests with marker proteins of known
      weight and pI verified the validity of the original findings. The method can be
      used for separation of isozymes and similarly sized proteins as an alternative to
      chromatofocusing or isoelectrofocusing.

PMID- 8533878
TI  - Poly(methacrylic acid)-induced liposome aggregation for measuring drug
      entrapment.
AB  - This report characterizes a procedure for rapidly and accurately determining the
      entrapment of vincristine or other water-soluble drugs in polyethylene glycol
      derivatized liposomes. Rapid liposome aggregation with poly(methacrylic acid) and
      pelleting by mild centrifugation separates liposome-associated vincristine from
      unentrapped drug. After collecting the supernatant fraction, the pellet is
      resuspended and solubilized in isopropyl alcohol. Quantitative uv
      spectrophotometry determines vincristine mass in both fractions. The mean
      accuracy (recovery) is 100.6% over an entrapped drug range from 70 to 99%. Within
      and between day precision of the method has a relative standard deviation of
      0.76% for a single measurement.

PMID- 8533879
TI  - A general method to recondition and reuse BIAcore sensor chips fouled with
      covalently immobilized protein/peptide.
AB  - Of significance in the routine use of BIAcore is the cost of the sensor chips.
      This is particularly evident during the phase of method development of an assay
      where it is not unusual to expend several chips in a day in attempts to optimize
      immobilization conditions for a novel peptide or protein. In addition, it is
      accepted practice to discard a chip once its ligand binding capacity has
      diminished to an unacceptable level. While the high cost of sensor chips has been
      addressed to some degree through the recent introduction of research-grade sensor
      chips, we were interested in assessing the possibility of regenerating or
      reconditioning sensor chips in order to allow them to be reused. In particular,
      we concerned ourselves with regenerating sensor chips onto which peptide or
      protein had been immobilized. Our aim was to develop a general procedure that
      would allow reuse of such chips but would not decrease ligand immobilization
      capacity or increase nonspecific ligand adsorption properties. We present a
      method which employs a combination of enzymatic (Pronase E) and chemical
      (bromoacetic acid) treatments of used sensor chips. Regeneration requires an
      overnight incubation of the sensor chip ex situ so that one can continue to
      perform BIAcore experiments. The data demonstrate that this simple two-step
      procedure substantially removes immobilized proteins such as IgG, Protein G, an
      HIV-1 envelope glycoprotein (gp 120) and a neoglycoprotein based on bovine serum
      albumin, as determined by reflectance measurements and X-ray photoelectron
      spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533880
TI  - Detection and quantitation of hexa-histidine-tagged recombinant proteins on
      western blots and by a surface plasmon resonance biosensor technique.
AB  - The use of short peptide affinity tag sequences has become commonplace for the
      expression and purification of recombinant proteins. Many of these tags are
      antibody epitopes and detection of tagged proteins via Western blots is
      straightforward. However, the most common affinity tag used at present for the
      expression of recombinant proteins is a hexa-histidine, or like sequence, which
      exhibits strong affinity for Ni(II). The one drawback of histidine-containing
      affinity tags is the inability to specifically detect such recombinant proteins
      on Western blots. Here we describe the synthesis and use of biotinyl
      nitrilotriacetic acid which, in combination with streptavidin-horseradish
      peroxidase, allows for the detection of hexa-histidine-tagged recombinant
      proteins on Western blots. In addition, we describe a surface plasmon resonance
      technique, employing a solid-phase Ni(II)-nitrilotriacetic acid complex, for the
      detection and quantitation of hexa-histidine-tagged recombinant proteins in
      solution. The surface plasmon resonance technique also allows for the oriented
      immobilization of the recombinant proteins for subsequent ligand interaction
      studies.

PMID- 8533881
TI  - Production of a nested set of glycosylphosphatidylinositol structures from a
      glycosylphosphatidylinositol-anchored protein.
AB  - Glycosylphosphatidylinositol (GPI) membrane anchors are synthesized in the
      endoplasmic reticulum of eukaryotic cells. Synthesis of the core GPI structure is
      achieved by the sequential transfer of monosaccharides and phosphoethanolamine to
      phosphatidylinositol. The assembly process can be reproduced in vitro using
      membrane preparations supplemented with sugar nucleotides. With one exception,
      however, none of the biosynthetic enzymes involved have been isolated. One
      impediment to progress in the isolation of these enzymes is the nonavailability
      of adequate amounts of partially assembled GPI structures for use as assay
      substrates. In this paper we present procedures to prepare these structures from
      a GPI-anchored protein. The methods described include selective dephosphorylation
      of the GPI-anchored variant surface glycoprotein from Trypanosoma brucei variant
      118 to generate Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6-myo
      inositol-P-dimyristoylglycerol (Man3GlcN-PI), followed by exoglycosidase
      treatments and N-acetylation to produce Man2GlcN-PI, Man1GlcN-PI, GlcN-PI, and
      GlcNAc-PI. Procedures are also described for the stabilization and purification
      of these structures. It is anticipated that the convenient preparation of this
      range of partially assembled GPIs will be useful not only in developing assays
      for the eventual purification of the GPI biosynthetic enzymes but will also
      contribute to evaluating the specificity of the phospholipases that hydrolyze GPI
      anchors.

PMID- 8533882
TI  - A chemiluminescence-flow injection analysis of serum 3-hydroxybutyrate using a
      bioreactor consisting of 3-hydroxybutyrate dehydrogenase and NADH oxidase.
AB  - We describe a simple method for the highly sensitive chemiluminescence--flow
      injection analysis of 3-hydroxybutyrate in serum using a bioreactor column
      consisting of the two immobilized enzymes, 3-hydroxybutyrate dehydrogenase and
      NADH oxidase. The method was based on measuring the level of chemiluminescence
      formed by the reaction of a luminol-hexacyanoferrate mixture with hydrogen
      peroxide. The hydrogen peroxide was produced by the NADH oxidase reaction from
      NADH which was formed in the conversion of 3-hydroxybutyrate to acetoacetate by
      the 3-hydroxybutyrate dehydrogenase reaction. Among three immobilized enzyme
      columns, a coimmobilized, small 3-hydroxybutyrate dehydrogenase/NADH oxidase
      bioreactor alone (2 x 20 mm i.d.) readily hydrolyzed all of the injected 3
      hydroxybutyrate into acetoacetate, although 3-hydroxybutyrate dehydrogenase
      catalyzed the reversible reaction. The present method generated linearity of the
      data up to 1.5 mM 3-hydroxybutyrate with satisfactory precision, reproducibility,
      and accurate reaction recoveries. The results from 3-hydroxybutyrate correlated
      satisfactorily with those obtained by other well-established methods. The
      coimmobilized 3-hydroxybutyrate dehydrogenase/NADH oxidase reactor unit showed
      good operational stability over a 5-week period, during which it was repeatedly
      used for 1500 analyses.

PMID- 8533883
TI  - Acetate: a contaminant in Hepes buffer.

PMID- 8533884
TI  - Rapid immunodetection on polyvinylidene fluoride membrane blots without blocking.
AB  - The data presented here (Fig. 2, Table 2) clearly demonstrate that wetting of
      Immobilon-P is not required for immunodetection of transferrin. It can be
      inferred that the immobilized transferrin undergoes sufficient rehydration at the
      molecular level to permit epitope recognition by the antibodies, even when the
      surrounding areas of PVDF remain hydrophobic. The hydrophobic blot procedure was
      compatible with blots prepared by both tank and semidry transfer and with the
      substrates BCIP/NBT and 4CN. Additionally, the binding specificity of
      antitransferrin antiserum was not altered in the hydrophobic blot protocol. Given
      the diversity of blocking agents, antibodies, and visualization systems
      available, optimization for specific reagent combinations may be necessary. The
      most important parameters will be the concentration of blocking agents and
      detergents used since either, depending on chemical properties and concentration,
      may cause the membrane to wet out during incubation. This procedure is not
      applicable to nitrocellulose membranes since surfactants are used in their
      manufacture specifically to cause wetting in aqueous buffers.

PMID- 8533885
TI  - Protease assay based on magnetic beads.

PMID- 8533886
TI  - Ultrathin horizontal sodium dodecyl sulfate zymography.

PMID- 8533887
TI  - Digitonin permeabilization of Saccharomyces cerevisiae cells for in situ enzyme
      assay.

PMID- 8533888
TI  - Microscale galacturonic acid assay.

PMID- 8533889
TI  - Measurement of bile salt aggregation equilibria using kinetic dialysis and
      spreadsheet modeling.
AB  - Bile salts initially self-associate into small aggregates such as dimers and
      trimers before forming micelles at higher concentrations. The very size of these
      small aggregates hampers quantitation of their formation. We have devised a
      method using kinetic dialysis measurements to quantitatively examine aggregation
      of bile salt at concentrations below 10 mM. Data for rate of dialysis versus
      concentration were fitted to hypothetical models of aggregation using a personal
      computer spreadsheet. For sodium taurocholate these data best fit a model of
      initial dimer and trimer formation with stepwise association constants of 100 and
      160, respectively. Addition of larger aggregates to the model did not improve the
      fit. For sodium taurodeoxycholate the data best fit a model which included not
      only dimers and trimers, but also tetramers or larger aggregates up to 10-mers
      with stepwise association constants of 40, 400, and 1700 for dimers, trimers, and
      tetramers, respectively. These data agree reasonably well with existing
      literature and suggest that kinetic dialysis with spreadsheet modeling is a
      useful technique for the study of bile salt aggregation at relatively low
      concentrations.

PMID- 8533890
TI  - Kinetic monitoring of enzymatic reactions in real time by quantitative high
      performance liquid chromatography-mass spectrometry.
AB  - The study of enzyme kinetics under steady-state conditions represents a common
      and very useful method for investigating the mechanisms of enzymatic reactions.
      We report the use of mass spectrometry (MS) coupled with HPLC for the kinetic
      analysis of enzymatic reactions in real time. The hydrolysis of dinucleotides
      with bovine pancreatic ribonuclease A (RNase A) and the substrate-specific
      hydrolysis of lactose with beta-galactosidase can be monitored using ion-spray
      (pneumatically assisted electrospray) mass spectrometry as a sensitive and
      specific detector for the native substrates. The resulting data can be used to
      calculate both KM and Vmax for each system. Kinetic parameters obtained for RNase
      A and beta-galactosidase paralleled those obtained by conventional techniques.
      These findings suggest the possibility of developing alternative techniques,
      based on mass spectrometric detection, for performing kinetic analyses of
      enzymatic processes where no simple spectrophotometric assay is feasible. In
      addition to enabling the determination of kinetic parameters for authentic
      substrates, and not chromogenic analogs, such assays would also be useful in
      situations where very high sensitivity and specificity are desired.

PMID- 8533891
TI  - Simultaneous determinations of histamine and N tau-methylhistamine by high
      performance liquid chromatography-chemiluminescence coupled with immobilized
      diamine oxidase.
AB  - A method for the simultaneous determinations of histamine and its metabolite N
      tau-methylhistamine by HPLC-chemiluminescence coupled with immobilized diamine
      oxidase was developed. The method was based on the determination of
      chemiluminescence formed by the reaction of a luminol-ferricyanide mixture in
      alkaline medium with hydrogen peroxide which is one of the metabolic products of
      histamine and N tau-methylhistamine formed by diamine oxidase. HPLC with
      postcolumn derivatization resulted in good separation of the two amines and gave
      linear relationships between the concentrations of both and their
      chemiluminescence intensities. The lower limits of chemiluminescent detection of
      histamine and N tau-methylhistamine were 5 and 10 pmol, respectively. The
      immobilized column showed good operational stability for more than 1 month,
      during which period 200 samples were analyzed. With this system, the histamine
      contents of the cerebral cortex, forestomach, glandular stomach, and kidney of
      Wistar rats were found to be 0.30, 58, 396, and 2.4 nmol/g wet wt, respectively.
      These values are very similar to those determined by HPLC-fluorometry. The N tau
      methylhistamine contents of these tissues were 0.36, 0.40, 0.72, and 3.8 nmol/g
      wet wt, respectively. This method will be useful for studying the roles of
      histamine in both brain and peripheral tissues.

PMID- 8533892
TI  - Enzyme-linked hyaluronectin: a unique reagent for hyaluronan assay and tissue
      location and for hyaluronidase activity detection.
AB  - Several techniques for assaying and localizing hyaluronan (HA), all based on the
      affinity to hyaluronan of proteins isolated from cartilage, chondrosarcoma, or
      brain, have been proposed. We show here that a unique reagent, alkaline
      phosphatase-linked hyaluronectin, can be used to assay hyaluronan in biological
      fluids or tissue extracts (enzyme-linked sorbent assay method) and to
      characterize it in cells or tissue sections in two steps: reagent incubation and
      staining. Results of assays in biological fluids or tissue extracts showed a good
      correlation with results of the previously described technique using antibodies
      to detect hyaluronectin bound to a plastic microtest plate (B. Delpech et al.,
      1985, Anal. Biochem. 149, 555-565) for both low concentrations (< 1 mg/liter, r =
      0.973, P < 0.001) and high concentrations (> 1 mg/liter, r = 0.953, P < 0.001).
      The interassay variations were 8.5% when the assay was performed at 4 degrees C
      and 18.5% at 37 degrees C. The intraassay variations under those conditions were,
      respectively, 14.4 and 6.5%. Tissue HA could be detected easily with the reagent,
      as shown in fetal tissues and in tumors. Specificity of the reaction was
      controlled either by blocking the reagent with an excess of hyaluronan (which was
      not possible with other glycosaminoglycans) or by destroying tissue hyaluronan
      with streptomyces hyaluronidase. Alkaline phosphatase-linked hyaluronectin was
      also used to assay hyaluronidase activity in several biological fluids. One-hour
      incubation of hyaluronidase preparations on HA-coated plates made it possible to
      detect as low as 1 mU bovine testis hyaluronidase and 0.1 mTRU streptomyces
      hyaluronidase. Four-hour incubation made it possible to detect activity in a
      1/12,500 dilution of human serum.

PMID- 8533893
TI  - A tandem-column chromatographic method for studying the interaction between
      ligands and their targets: lipopolysaccharide as a model.
AB  - The identification of a lead ligand from a library of compounds for a specific
      target requires both a selection process and a method to assess relative
      affinities. Using a tandem-column chromatographic technique, we have developed a
      novel and rapid method for determination of relative affinities for ligands
      binding to a specific target molecule. We demonstrate, using known ligands for
      the lipid A region of lipopolysaccharide, that the relative affinities of these
      ligands can be determined and may be used to characterize the competitive
      interaction between ligands for the same target. The method can be adapted toward
      screening of soluble libraries of peptides and small molecules and those ligands
      exhibiting a desired affinity can be rapidly selected for further
      characterization/development.

PMID- 8533894
TI  - Automation of a high-performance liquid chromatography-based enzyme assay:
      evaluation of inhibition constants for human immunodeficiency virus-1 protease
      inhibitors.
AB  - Enzyme-based assays are commonly employed in clinical and pharmaceutical
      laboratories to aid in quantitation of organic substances. Many enzyme assays are
      tedious, requiring the addition of reagents at multiple time intervals. The HPLC
      based analysis of reaction products requires an additional step of vialing the
      samples and placing them in the autosampler. Such time-consuming, repetitive
      procedures are ideally suited for automation. We automated an HIV protease assay
      for the purposes of screening compounds as inhibitors of HIV protease and
      determining inhibition constants. Automation was accomplished by interfacing a
      robotic sample processor from a Gilson Model 232/401 biocompatible automatic
      sample processor and injector, with a Hewlett Packard HPLC. We used this
      configuration to automate the following steps: (a) preparation of serial
      dilutions of inhibitor, (b) enzyme assay setup, and (c) quantitation of products
      of enzyme assays. The resulting automated method produced inhibition constants
      that were of comparable accuracy and precision to those determined by manual
      methods.

PMID- 8533895
TI  - Use of alpha-N,N-bis[carboxymethyl]lysine-modified peroxidase in immunoassays.
AB  - Horseradish peroxidase was activated by periodate oxidation of the carbohydrate
      moiety and then modified by the covalent attachment of alpha-N,N
      bis[carboxyethyl]lysine (CM-Lys) by reductive alkylation using sodium
      cyanoborohydride. The resultant CM-Lys peroxidase was charged with nickel ions
      and then used as a specific labeling reagent for histidine-tagged recombinant
      proteins. This labeling method was effective for proteins that are soluble or
      insoluble in the absence of chaotropic agents. The labeled proteins were very
      effective in direct sandwich enzyme-linked immunosorbent assay for detecting
      antibodies against the protein in sera as demonstrated by assays for antibodies
      to such diverse viral proteins as hepatitis B surface and core proteins,
      hepatitis C core and helicase protein (NS3), and retroviral core proteins.

PMID- 8533896
TI  - Synthesis of a radioiodinated photoreactive MAGE-1 peptide derivative and
      photoaffinity labeling of cell-associated human leukocyte antigen-A1 molecules.
AB  - The synthesis of a photoreactive derivative of the human leukocyte antigen-A1
      (HLA-A1)-restricted MAGE-1 peptide 161-169 (EADPTGHSY) is described. Using
      conventional automated solid-phase peptide synthesis, a photoreactive derivative
      of this peptide was synthesized by replacing histidine-167 with photo-reactive N
      beta-4-azidosalicyloyl-L-2,3-diaminopropionic acid. The C-terminal tyrosine was
      incorporated as phosphotyrosine. This peptide derivative was radioiodinated in
      the presence of chloramine T. This iodination took place selectively at the
      photoreactive group, because the phosphate ester prevented tyrosine iodination.
      Following dephosphorylation with alkaline phosphatase and chromatographic
      purification, the radiolabeled peptide derivative was incubated with cells
      expressing HLA-A1 or other HLA molecules. Photoactivation resulted in efficient
      photoaffinity labeling of HLA-A1. Other HLA molecules or other cellular
      components were not detectably labeled. This labeling was inhibited by HLA-A1 but
      not by HLA-A2-binding peptides. This synthesis is generally applicable and can
      also be adapted to the synthesis of well-defined radiolabeled nonphotoreactive
      peptide derivatives.

PMID- 8533897
TI  - Development of a biologically active fluorescent-labeled calcitriol and its use
      to study hormone binding to the vitamin D receptor.
AB  - To gain better insight into the mechanism of steroid receptor activation and
      calcitriol action, we have developed the first pharmacologically relevant
      fluorescent-labeled ligand for the vitamin D receptor (VDR). Purity and structure
      of three BODIPY-labeled calcitriol derivatives were characterized by TLC, HPLC,
      and 1H-NMR spectroscopy. 3 beta-BODIPY-calcitriol was the most potent derivative
      to induce 25-hydroxyvitamin D3 24-hydroxylase activity and to inhibit cell
      proliferation. It was taken up rapidly and specifically and was not cleaved by
      endogenous esterases. 3 beta-BODIPY-calcitriol also retained high-affinity
      binding to the VDR. Hormone binding to the receptor was measured by
      spectrofluorometry in high-salt extracts from cultured cells with wild-type VDR,
      from cells virally over-expressing the human VDR, and in intact cells with and
      without VDR. Results from fluorescent binding studies agreed with results from
      radioligand assays. The most useful feature of this reagent is that its
      fluorescence emission increases severalfold upon binding to VDR. This allows
      direct monitoring by microscopy of ligand receptor interactions in living cells.
      Fluorescent-labeled calcitriol can be a valuable diagnostic tool for cancer
      research and is essential for exploring the subcellular localization of VDRs.

PMID- 8533898
TI  - PhosphorImager enhancement of sedimentation equilibrium-quantitative
      polyacrylamide gel electrophoresis: a highly sensitive technique for quantitation
      of equilibrium gradients of individual components in mixtures.
AB  - The technique called sedimentation equilibrium-quantitative polyacrylamide gel
      electrophoresis (Darawshe et al. (1993) Anal. Biochem. 215, 236-242) has been
      extended to permit the quantitation and analysis of gradients of individual
      radiolabeled components in a mixture of radiolabeled solutes centrifuged to
      sedimentation equilibrium. Immediately following centrifugation, the contents of
      a sample tube are fractionated into aliquots corresponding to laminae of solution
      at different radial positions in the centrifuge. Following treatment with sodium
      dodecyl sulfate-containing buffer, a portion of each fraction is subjected to
      electrophoresis on a polyacrylamide gel. The gel is then incubated with a strong
      phosphor plate and subsequently scanned with a Molecular Dynamics PhosphorImage.
      The concentration of an individual radiolabeled component at a particular radial
      distance is proportional to the integrated intensity of the image of the
      radiolabeled band of that component in the fraction corresponding to that radial
      distance. Concentration gradients reconstructed in this fashion are interpreted
      in the context of conventional sedimentation equilibrium theory. The results of
      control experiments carried out with purified proteins of known molar mass and
      the measurement of the molar mass of a new, partially purified protein are
      reported.

PMID- 8533899
TI  - A colorimetric assay for xyloglucan-endotransglycosylase from germinating seeds.
AB  - One of the key enzymes involved in the breakdown of reserve xyloglucan in seeds
      of some dicotyledonous plants during germination is the specific endo-beta-(1,4)
      glucanase. The enzyme operates predominantly by a transglycosylic mechanism,
      i.e., by random splitting the beta-(1,4)-linked polyglucose backbone of
      xyloglucan molecules and rejoining the newly created reducing ends by beta-(1,4)
      glycosidic bonds to nonreducing ends of other xyloglucan molecules or xyloglucan
      subunit oligosaccharides. For this reason, the enzyme is regarded primarily as
      xyloglucan-endotransglycosylase (XET). Since almost no net formation of reducing
      ends occurs in the course of transglycosylation, the conventional reductometric
      methods used for the assessment of glycanase activities are not applicable for
      detection and determination of XET activity. The described colorimetric assay is
      based on the property of xyloglucan-derived subunit oligosaccharides (DP 5-10) to
      stimulate selectively the breakdown of xyloglucan by endotransglycosylation while
      serving as additional glycosyl acceptors. The depolymerization of xyloglucan in
      the course of reaction is followed colorimetrically by measuring the
      disappearance of the blue--green-colored iodine:xyloglucan complex. The
      transglycosylase activity is calculated as the difference of activities measured
      in the presence of stimulating xyloglucan-derived oligosaccharides and in their
      absence. The advantages of the described colorimetric method include its low
      cost, simplicity, speed, and the possibility to analyze multiple samples
      simultaneously.

PMID- 8533900
TI  - A microfluorometric method for measuring ethoxycoumarin-O-deethylase activity on
      individual Drosophila melanogaster abdomens: interest for screening resistance in
      insect populations.
AB  - We developed a method for measuring ethoxycoumarin deethylase (ECOD) activity
      using a single Drosophila abdomen. The activities obtained were well correlated
      with the classic method from microsomes (r = 0.902). This new method, performed
      in microtitration plates, was at least six times more sensitive compared to the
      conventional cuvet fluorometric one. Moreover, it was possible among a large
      number of insects to differentiate those with low or high ECOD activities. This
      improved procedure has been checked upon crosses between resistant strain (with
      high ECOD activity) and susceptible strain (with low ECOD activity). The results
      demonstrate the possible separation of resistant phenotypes and emphasize the
      importance of this approach in assessing the spreading of insecticide resistance
      in natural populations of insects.

PMID- 8533901
TI  - Production of membrane vesicles by extrusion: size distribution, enzyme activity,
      and orientation of plasma membrane and chloroplast inner-envelope membrane
      vesicles.
AB  - A comparison of plasma membrane vesicles prepared by a freeze/thaw method was
      made with vesicles prepared by extrusion through a 100-nm polycarbonate filter.
      Based on ATPase measurements in the presence or absence of detergent, plasma
      membrane vesicles were approximately 30% right-side-out in freeze/thaw vesicles,
      whereas vesicles produced by extrusion were approximately 80% right-side-out.
      Chloroplast inner-envelope membrane vesicles were loaded with a membrane
      impermeant, pH-sensitive fluorophore, pyranine, by either freeze/thaw or
      extrusion techniques. ATP-linked proton transport activity was considerably lower
      in vesicles prepared by extrusion compared to vesicles prepared by freeze/thaw.
      However, total ATPase activity measured as ADP release from ATP was equivalent in
      both preparations of vesicles. These results suggest that the inner-envelope
      vesicles produced by extrusion were predominantly oriented right-side-out. Inner
      envelope vesicles were loaded internally with phosphate to study proton-linked
      transport of 3-phosphoglycerate. Vesicle acidification by 3-phosphoglycerate
      addition was similar in both freeze/thaw and extruded vesicle preparations,
      indicating that metabolite transport by the phosphate translocator is both
      functional and bidirectional. These results indicate that extrusion can be used
      as a method to produce proteoliposomes which are competent for transport studies.

PMID- 8533902
TI  - Selection of high-affinity binding sites for sequence-specific, DNA binding
      proteins from random sequence oligonucleotides.
AB  - We describe a rapid and sensitive method to isolate sets of high-affinity binding
      sites for sequence-specific DNA binding proteins. The DNA binding domain of the
      protein is expressed in Escherichia coli as a fusion with glutathione S
      transferase (GST). Binding reactions are set up with total soluble extract from
      induced bacteria and a double-stranded oligonucleotide for which the central 32
      bp have been randomized. To ensure stringent conditions, binding is done in the
      presence of high levels of poly(dI:C). The GST fusion protein is recovered by the
      addition of glutathione-Sepharose. Following extensive washing of the Sepharose
      beads, the bound oligonucleotides are rescued by polymerase chain reaction
      amplification. The amplified material is used in the next cycle of selection and
      amplification. Approximately five cycles are needed to obtain a pure population
      of high-affinity sites, which are then cloned and sequenced. This procedure
      should be applicable to any sequence-specific DNA binding protein for which the
      cDNA is available and which can be expressed in bacteria in a functional form.

PMID- 8533903
TI  - Meaningful cost reduction. Penny wise, pound foolish.

PMID- 8533904
TI  - Where are the costs in perioperative care? Analysis of hospital costs and charges
      for inpatient surgical care.
AB  - BACKGROUND: Many health-care institutions are emphasizing cost reduction programs
      as a primary tool for managing profitability. The goal of this study was to
      elucidate the proportion of anesthesia costs relative to perioperative costs as
      determined by charges and actual costs. METHODS: Costs and charges for 715
      inpatients undergoing either discectomy (n = 234), prostatectomy (n = 152),
      appendectomy (n = 122) or laparoscopic cholecystectomy (n = 207) were
      retrospectively analyzed at Stanford University Medical Center from September
      1993 to September 1994. Total hospital costs were separated into 11 hospital
      departments. Cost-to-charge ratios were calculated for each surgical procedure
      and hospital department. Hospitalization costs were also divided into variable
      and fixed costs (costs that do and do not change with patient volume). Costs were
      further partitioned into direct and indirect costs (costs that can and cannot be
      linked directly to a patient). RESULTS: Forty-nine (49%) percent of total
      hospital costs were variable costs. Fifty-seven (57%) percent were direct costs.
      The largest hospital cost category was the operating room (33%) followed by the
      patient ward (31%). Intraoperative anesthesia costs were 5.6% of the total
      hospital cost. The overall cost-to-charge ratio (0.42) was constant between
      operations. Cost-to-charge ratios varied threefold among hospital departments.
      Patient charges overestimated resource consumption in some hospital departments
      (anesthesia) and underestimated resource consumption in others (ward).
      CONCLUSIONS: Anesthesia comprises 5.6% of perioperative costs. The influence of
      anesthesia practice patterns on "downstream" events that influence costs of
      hospitalization requires further study.

PMID- 8533905
TI  - Nitroprusside inhibition of platelet function is transient and reversible by
      catecholamine priming.
AB  - BACKGROUND: The time course and reversibility of sodium nitroprusside's in vivo
      inhibition of platelet function are unclear. METHODS: Platelet aggregation and P
      selectin expression as measures of platelet dense and alpha-granule release,
      respectively, were examined before and after administration of sodium
      nitroprusside (18 mg) to human volunteers and in in vitro studies. Hypotension
      occurring with sodium nitroprusside administration was treated with intravenous
      crystalloid and/or phenylephrine. RESULTS: Compared with preinfusion studies,
      platelet aggregation to epinephrine was significantly inhibited immediately and 4
      min after discontinuation of the sodium nitroprusside infusion but returned to
      baseline at 8 and 12 min after discontinuing sodium nitroprusside. However, both
      dense and alpha-granule release to adenosine diphosphate after in vivo sodium
      nitroprusside were never significantly inhibited even at the time when sodium
      nitroprusside infusion was maximal. In contrast to our in vivo findings, in vitro
      incubation of platelet-rich plasma with sodium nitroprusside resulted in
      significant inhibition of dense and alpha-granule release to adenosine
      diphosphate. These in vitro inhibitory effects of sodium nitroprusside were
      reversed by pretreatment with epinephrine but not phenylephrine. CONCLUSIONS: In
      normal volunteers, sodium nitroprusside inhibits platelet aggregation to
      epinephrine but not adenosine diphosphate; inhibition was reversed within 8-12
      min after discontinuing sodium nitroprusside. Sodium nitroprusside in vitro
      inhibition of platelet function to adenosine diphosphate was reversed by
      epinephrine pretreatment. Because of the rapid reversibility of its antiplatelet
      effect, sodium nitroprusside may be clinically useful even when there is the
      potential for impaired coagulation.

PMID- 8533906
TI  - Inhaled nitric oxide reduces pulmonary transvascular albumin flux in patients
      with acute lung injury.
AB  - BACKGROUND: In acute lung injury, when pulmonary microvascular permeability is
      enhanced, transvascular fluid filtration mainly depends on pulmonary capillary
      pressure. Inhaled nitric oxide has been shown to decrease pulmonary capillary
      pressure. Therefore, the effect of inhaled nitric oxide at a concentration of 40
      ppm on pulmonary transvascular albumin flux was studied in nine patients with
      acute lung injury. METHODS: Transvascular albumin flux was measured by a double
      radioisotope method using 99mTc-labeled albumin and 51Cr-labeled autologous red
      blood cells. Radioactivity of both isotopes was externally measured over the
      right lung by a gamma scanner and simultaneously in arterial blood. The
      normalized ratio of 99mTc/51Cr lung to 99mTc/51Cr blood (normalized index) was
      calculated. The normalized slope index which is the slope of the regression line
      of the normalized index versus time represents the accumulation rate of albumin
      in the interstitial space of the lungs. Normalized slope index and pulmonary
      capillary pressure were determined before, during, and after inhalation of 40 ppm
      nitric oxide. Pulmonary capillary pressure was estimated using the visual
      analysis of the pressure decay curve after pulmonary artery occlusion. RESULTS:
      Normalized slope index decreased from 0.0077 +/- 0.0054 min-1 (SD) off nitric
      oxide to -0.0055 +/- 0.0049 min-1 (P < 0.01) during nitric oxide and increased to
      0.0041 +/- 0.0135 min-1 after nitric oxide. Pulmonary capillary pressure declined
      from 24 +/- 4 mmHg off nitric oxide to 21 +/- 4 mmHg during nitric oxide (P <
      0.01), whereas pulmonary artery wedge pressure and cardiac output did not change.
      CONCLUSIONS: It is concluded that 40 ppm inhaled nitric oxide decreases pulmonary
      transvascular albumin flux in patients with acute lung injury. This effect may be
      the result of the decrease in pulmonary capillary pressure.

PMID- 8533907
TI  - Shivering threshold during spinal anesthesia is reduced in elderly patients.
AB  - BACKGROUND: Both accidental and perioperative hypothermia are common in the
      elderly. The elderly are at risk because their responses to hypothermia may be
      delayed or less efficient than in those of younger subjects. For example, the
      vasoconstriction threshold during isoflurane anesthesia is approximately 1 degree
      C less in elderly than younger patients. However, the extent to which other cold
      defenses are impaired in the elderly remains unclear, especially in those older
      than 80 yr. Operations suitable for spinal anesthesia provided an opportunity to
      quantify shivering thresholds in patients of varying ages. Accordingly, the
      hypothesis that the shivering threshold is reduced as a function of age during
      spinal anesthesia was tested. METHODS: Twenty-eight ASA Physical Status 1-3
      patients undergoing lower extremity orthopedic procedures were studied. Spinal
      anesthesia was induced without preanesthetic medication, using bupivacaine
      sufficient to produce a dermatomal level near T9. Electrocardiogram signals were
      recorded at 10-min intervals. Subsequently, an observer masked to patient age and
      core temperature identified the onset of sustained electromyographic artifact
      consistent with shivering. The tympanic membrane temperature triggering shivering
      identified the threshold. RESULTS: Three patients did not shiver at minimum core
      temperatures exceeding 36.2 degrees C. Fifteen patients aged < 80 yr (58 +/- 10
      yr) shivered at 36.1 +/- 0.6 degrees C; in contrast, ten patients aged > or = 80
      yr (89 +/- 7 yr) shivered at a significantly lower mean temperature, 35.2 +/- 0.7
      degrees C (P = 0.002). The shivering thresholds in seven of the ten patients
      older than 80 yr was less than 35.5 degrees C, whereas the threshold equaled or
      exceeded this value in all younger patients (P = 0.0002). CONCLUSIONS: Age
      dependent inhibition of autonomic thermoregulatory control in the elderly might
      be expected to result in hypothermia. That it usually does not suggests that
      behavioral regulation (e.g., increasing ambient temperature, dressing warmly)
      compensates for impaired autonomic control. Elderly patients undergoing spinal
      anesthesia, however, may be especially at risk of hypothermia because low core
      temperatures may not trigger protective autonomic responses. Furthermore,
      hypothermia in the elderly given regional anesthesia may not be perceived by the
      patient (who typically feels less cold after induction of the block), or by the
      anesthesiologist (who does not observe shivering). Consequently, temperature
      monitoring and management usually is indicated in these patients.

PMID- 8533908
TI  - Effects of storage time on quantitative and qualitative platelet function after
      transfusion.
AB  - BACKGROUND: Platelet transfusions are being used increasingly in patients with
      thrombocytopenia to improve hemostatic function before surgery and invasive
      procedures. However, there are limited data on the immediate quantitative and
      qualitative platelet response after transfusion. Some authors have suggested that
      transfused platelets require time in vivo to regain maximal function, which is
      dependent on the duration of platelet storage. Therefore, the timing of surgery
      and invasive procedures with optimal platelet function may not be occurring.
      METHODS: Twenty-five patients with thrombocytopenia from ablation chemotherapy
      and total body irradiation (before bone marrow transplantation), were randomized
      to receive either 1-day (fresh) or 4-day stored platelets. No patient had
      infection, organ system dysfunction, or previous platelet transfusion. Single
      donor platelets were transfused (1 unit/10 kg body weight) over 60 min. Whole
      blood from an indwelling central venous catheter was obtained before, immediately
      after, and 1, 2, and 24 h after transfusion. Platelet number was measured on a
      Coulter counter and platelet reactivity was measured on a Coulter counter and
      platelet reactivity was measured using agonist-induced whole blood impedance
      aggregometry (ohms) and dense granule release (adenosine triphosphate [ATP]).
      RESULTS: Platelet number increased similarly (21,000 +/- 2,000/mm3 to 76,000 +/-
      7,000/MM3 AND 20,000 +/- 1,000/MM3 TO 65,000 +/- 4,000/MM3) after transfusion in
      the 1- and 4-day stored platelets, respectively. These levels were maintained for
      2 h after transfusion in both groups and then decreased similarly (26% and 27%)
      at 24 h. Agonist-induced platelet aggregation increased immediately after
      transfusion to 5 micrograms/ml collagen (0.7 +/- 0.4 to 11.4 +/- 1.0 ohms and 0.1
      +/- 0.1 to 5.2 +/- 1.0 ohms), 10 micrograms/ml collagen, (1.5 +/- 0.7 to 18.0 +/-
      1.9 ohms and 0.6 +/- 0.4 to 10.0 +/- 1.6 ohms) and ristocetin (0.7 +/- 0.4 to
      10.1 +/- 1.7 and 0.1 +/- 0.7 to 6.2 +/- 1.0 ohms), in 1- and 4-day, stored
      platelets, respectively and persisted unchanged in both groups for 2 h. Fresh
      platelets were hyperaggregable compared to 4-day stored platelets for collagen
      induced (5 micrograms/ml and 10 micrograms/ml) aggregation. Agonist-induced
      platelet dense granule release (ATP) increased immediately after transfusion to 5
      micrograms/ml collagen (42 +/- 18 to 410 +/- 49 picomoles ATP and 20 +/- 7 to 186
      +/- 22 picomoles ATP), 10 micrograms/ml collagen (60 +/- 22 to 449 +/- 53
      picomoles ATP and 44 +/- 13 to 219 +/- 25 picomoles ATP in 1- and 4-day
      platelets, respectively. Ristocetin-induced ATP release increased immediately
      after transfusion of fresh platelets only (0 +/- 0 to 69 +/- 17) and remained
      unchanged for 2 h. Fresh platelets also demonstrated greater dense granule
      release to collagen (5 micrograms and 10 micrograms/ml) and ristocetin than 4-day
      stored platelets. CONCLUSIONS: In patients with chemotherapy-induced
      thrombocytopenia, platelet transfusion causes an immediate increase in number and
      function, which is independent of storage time. This quantitative and qualitative
      increase persists unchanged for 2 h after transfusion, suggesting that there is
      no acute "warm-up-time" necessary for transfused platelets to regain maximal
      function. Fresh platelets demonstrate increased aggregation and dense granule
      release compared to 4-day stored platelets and may impart improved hemostatic
      function in vivo.

PMID- 8533909
TI  - Cardiovascular stimulation induced by rapid increases in desflurane concentration
      in humans results from activation of tracheopulmonary and systemic receptors.
AB  - BACKGROUND: It was hypothesized that stimulation of rapidly adapting airway
      receptors produces the transient (2-4 min) circulatory responses to rapid
      increases in desflurane concentrations greater than 6%. Accordingly, it was
      reasoned that increasing the concentration of desflurane in one lung, without
      altering the concentration of desflurane in systemic blood, should cause
      cardiovascular stimulation, whereas once the airway receptors had adapted to the
      stimulation, an initial increase in the systemic concentration of desflurane
      should have little effect. METHODS: After placement of a double-lumen
      endotracheal tube in four volunteers and establishment of a steady-state level of
      4% desflurane in both lungs, the desflurane concentration was rapidly increased
      from 4% to 8% in one lung while decreasing it in the other, thereby obviating any
      increase in the systemic desflurane blood concentration (confirmed by analysis).
      After returning the desflurane end-tidal concentration to 4% in both lungs, this
      process was repeated for the contralateral lung thereby having exposed both lungs
      to 8% desflurane without increasing the systemic desflurane concentration. After
      returning desflurane concentration to 4%, it was increased in both lungs
      simultaneously to 8% and consequently in blood to 8% of an atm. RESULTS: Rapid
      increases in desflurane concentrations in either lung, but not blood,
      significantly increased heart rate (17 +/- 5 beats/min, mean +/- SE, P < 0.05)
      and mean arterial blood pressure (15 +/- 5 mmHg, P < 0.05), but a greater
      increase in heart rate (43 +/- 5 beats/min, P < 0.05) and mean arterial blood
      pressure (46 +/- 11 mmHg, P < 0.05) occurred when both lungs were exposed
      simultaneously to rapidly increased desflurane concentration for the second time
      within 90 min. This result did not differ from the increase occurring on another
      day when both lungs and blood were exposed for the first time that day to 8%
      desflurane (heart rate 40 +/- 7 beats/min, P = 0.8; mean arterial blood pressure
      40 +/- 3 mmHg, P = 0.5). CONCLUSIONS: It was concluded that at least two sites
      respond to a rapid increase in desflurane concentrations greater than 6%: one
      site in the airways and/or lungs, and at least one other in a highly perfused
      tissue(s). The systemic site contributes more importantly.

PMID- 8533910
TI  - Premedication with famotidine augments core hypothermia during general
      anesthesia.
AB  - BACKGROUND: Animal studies have provided considerable evidence to support a role
      of histamine in the central nervous system in thermoregulation, and premedication
      with a histamine H2 receptor antagonist before general anesthesia is used to
      reduce the risk of acid aspiration. The authors investigated whether
      premedication with famotidine had an effect on thermoregulation during general
      anesthesia. METHODS: In a randomized, placebo-controlled study, 30 ASA physical
      status 1 or 2 patients, scheduled for open abdominal surgery, were given either
      placebo or 40 mg oral famotidine 3 h before induction of anesthesia. Epidural
      buprenorphine (4 micrograms/kg) was injected, and anesthesia was maintained with
      0.4-0.6% isoflurane and 66% nitrous oxide in oxygen. The tympanic membrane
      temperature was measured to assess core temperature, and forearm-fingertip and
      calf-toe skin-surface temperature gradients were used to assess peripheral
      vasoconstriction. Tympanic membrane temperature triggering initial
      vasoconstriction (a skin temperature gradient of 0 degree C) identified the
      vasoconstriction threshold. RESULTS: Tympanic membrane temperature during surgery
      in the patients premedicated with famotidine was significantly less than those in
      the patients without famotidine. Famotidine significantly reduced the
      thermoregulatory threshold for vasoconstriction in the leg (35.0 +/- 0.5 degree
      C, P < 0.05), compared to that in the placebo group (36.4 +/- 0.6 degree C) Once
      triggered, thermoregulatory vasoconstriction produced a core-temperature plateau
      and no further hypothermia was observed for the duration of the study. Neither
      mean arterial pressure nor heart rate were significantly different between the
      two groups. CONCLUSIONS: Premedication with famotidine augments intraoperative
      hypothermia. The mechanism appears to be inhibition of centrally mediated
      thermoregulatory control.

PMID- 8533911
TI  - Visual display format affects the ability of anesthesiologists to detect acute
      physiologic changes. A laboratory study employing a clinical display simulator.
AB  - BACKGROUND: Anesthesiologists use data presented on visual displays to monitor
      patients' physiologic status. Although studies in nonmedical fields have
      suggested differential effects on performance among display formats, few studies
      have examined the effect of display format on anesthesiologist monitoring
      performance. METHODS: A computer-based clinical display simulator was developed
      to evaluate the efficacy of three currently used display formats (numeric,
      histogram, or polygon displays) in a partial-task laboratory simulation. The
      subjects' task consisted solely of detecting any changes in the values of the
      physiologic variables depicted on a simulated clinical display. Response latency
      and accuracy were used as measures of performance. RESULTS: Thirteen anesthesia
      residents and five nonmedical volunteers, were enrolled as subjects. Use of
      either the histogram or polygon displays significantly improved response
      latencies and allowed greater accuracy compared with the numeric display in the
      anesthesia residents. Neither response latency nor accuracy improved with
      additional exposure to these displays. In contrast, display format did not
      significantly affect response latency or accuracy in the nonmedical volunteers.
      CONCLUSIONS: The results of this study suggest that graphic displays may enhance
      the detection of acute changes in patient physiologic status during anesthesia
      administration. This research also demonstrates the importance of assessing
      performance on clinical devices by studying actual users rather than random
      subjects. Further research is required to elucidate the display elements and
      characteristics that best support different aspects of the anesthesiologist's
      monitoring tasks.

PMID- 8533912
TI  - Linearity of pharmacokinetics and model estimation of sufentanil.
AB  - BACKGROUND: The pharmacokinetic profiles of sufentanil available in the
      literature are conflicting because of methodologic differences. Length of
      sampling and assay sensitivity are key factors involved in accurately estimating
      the volumes of distribution, clearances, and elimination phase. The unit
      disposition function of increasing doses of sufentanil were investigated and the
      influence of dose administered on the linearity of pharmacokinetics was assessed.
      METHODS: The pharmacokinetics of sufentanil were investigated in 23 patients,
      aged 14-68 yr, scheduled for surgery with postoperative ventilation. After
      induction of anesthesia, sufentanil was administered as a short infusion (10-20
      min) in doses ranging from 250 micrograms to 1,500 micrograms. Frequent arterial
      blood samples were gathered during and at the end of infusion, then at specific
      intervals up to 48 h after infusion. Plasma concentrations of sufentanil were
      measured by radioimmunoassay (limit of sensitivity 0.02 ng.ml-1). The data were
      analyzed with the standard two-stage, naive pooled-data and the mixed effect
      pharmacokinetic approaches. RESULTS: The pharmacokinetics of sufentanil were
      adequately described by a linear three-compartmental mamillary model with the
      following parameters, expressed as log mean values with 95% confidence intervals:
      the central volume of distribution = 14.3 l (13.1-15.41), the rapidly
      equilibrating volume = 63.1 l (61.9-64.3 l), the slowly equilibrating volume =
      261.6 l (260.2-262.9 l), the steady-state distribution volume = 339 l (335-343
      l), metabolic clearance = 0.92 l.min-1 (0.84-1.05 l.min-1), rapid distribution
      clearance = 1.55 l.min-1 (1.34-2.14 l.min-1), slow distribution clearance = 0.33
      l.min-1 (0.27-0.49 l.min-1), and elimination half-life = 769 min (690-1011 min).
      No relation to age, weight, or lean body mass was found for any of the
      parameters. CONCLUSIONS: Sufentanil pharmacokinetics were linear within the dose
      range studied. Drug detection up to 24 h after dosing was necessary to define the
      terminal elimination phase. The metabolic clearance approached liver blood flow
      and a large volume of distribution was identified, consistent with the long
      terminal elimination half-life. Simulations predicted that plasma sufentanil
      steady-state concentrations would rapidly decline after termination of an
      infusion despite the long half-lives.

PMID- 8533913
TI  - Desflurane slightly increases the sweating threshold but produces marked,
      nonlinear decreases in the vasoconstriction and shivering thresholds.
AB  - BACKGROUND: Shivering is rare during general anesthesia. This observation
      suggests that anesthetics profoundly impair shivering. However, the effects of
      surgical doses of volatile anesthetics on control of shivering have yet to be
      evaluated. Furthermore, the effects of desflurane on sweating and
      thermoregulatory vasoconstriction remain unknown. Accordingly, the authors
      determined the concentration-dependent effects of desflurane on sweating,
      vasoconstriction, and shivering. METHODS: Nine volunteers each were studied on
      three randomly ordered days: (1) control (no anesthesia); (2) a target end-tidal
      desflurane concentration of 0.5 minimum alveolar concentration (MAC; 3.5%); and
      (3) a target concentration of 0.8 MAC (5.6%). Each day, volunteers were warmed
      until sweating was induced and subsequently cooled until peripheral
      vasoconstriction and shivering was observed. Changes in skin temperature were
      arithmetically compensated using the established linear cutaneous contributions
      to control of each response. From the calculated thresholds (core temperatures
      triggering responses at a designated skin temperature of 34 degrees C), the
      concentration-response relationship was determined. RESULTS: Desflurane
      significantly and linearly increased the sweating threshold from 37.1 +/- 0.3
      degrees C on the control day (mean +/- SD), to 37.6 +/- 0.4 degrees C at 0.5 MAC,
      and to 38.1 +/- 0.3 degrees C at 0.8 MAC. Desflurane significantly, but
      nonlinearly, reduced the vasoconstriction and shivering thresholds. The sweating
      to-vasoconstriction (interthreshold) range thus increased from 0.5 +/- 0.3
      degrees C to 2.3 +/- 0.7 degrees C at 0.5 MAC and further to 4.6 +/- 2.0 degrees
      C at 0.8 MAC. The vasoconstriction-to-shivering range (difference between the
      respective thresholds) remained between 1.1 and 1.5 degrees C on the three study
      days. CONCLUSIONS: The observed linear increase in the sweating threshold was
      similar in pattern and magnitude to that produced by most general anesthetics.
      The approximately 3 degrees C reduction in the vasoconstriction threshold by 0.8
      MAC desflurane was similar to that observed previously during isoflurane and
      propofol anesthesia. However, the threshold was reduced less than expected at 0.5
      MAC, suggesting that the dose-response relationship for vasoconstriction is
      nonlinear. Shivering was induced without difficulty in this study although the
      response is rare in surgical patients. It is likely that shivering during general
      anesthesia is rare because thermoregulatory vasoconstriction usually prevents
      body temperature from decreasing the required additional 1-1.5 degrees C.

PMID- 8533914
TI  - Desflurane reduces the gain of thermoregulatory arteriovenous shunt
      vasoconstriction in humans.
AB  - BACKGROUND: Thermoregulatory responses, such as arteriovenous shunt
      vasoconstriction, provide substantial protection against core hypothermia. A
      response can be characterized by its threshold (core temperature triggering
      response), gain (rate at which response intensity increases, once triggered), and
      maximum response intensity. Reduced gain decreases the efficacy of a
      thermoregulatory response at a given threshold because response intensity will
      increase more slowly than usual. The effects of general anesthesia on the gain of
      arteriovenous shunt vasoconstriction have not been reported. Accordingly, we
      tested the hypothesis that desflurane decreases the gain of centrally mediated
      vasoconstriction. METHODS: We studied seven healthy male volunteers. Each was
      studied twice: (1) desflurane (end-tidal concentration 0.4 minimum alveolar
      concentration); and (2) control (no anesthesia). Mean skin and fingertip
      temperatures were controlled at 35.5 degrees C throughout the study. Core
      temperature was reduced at a rate of 1.5 degrees C/h by central venous infusion
      of cold fluid. Fingertip arteriovenous shunt flow was measured using venous
      occlusion volume plethysmography at 1-min intervals. Flow was also evaluated
      using the perfusion index and laser Doppler flowmetry. Vasoconstriction
      thresholds were calculated as the core temperatures triggering fingertip flows of
      1.0 ml/min (beginning of vasoconstriction) and 0.25 ml/min (intense
      vasoconstriction). The gain of vasoconstriction was considered to be the slope of
      the fingertip flow versus core temperature regression within the linear range
      from 1.0 ml/min to 0.15 ml/min. The minimum observed flow was considered maximum
      vasoconstriction intensity. Data are presented as means +/- SD; P < 0.01 was
      considered statistically significant. RESULTS: The vasoconstriction threshold
      (when defined using a flow of 1.0 ml/min) was reduced from 36.8 +/- 0.3 degrees C
      to 35.6 +/- 0.3 degrees C by desflurane anesthesia (P < 0.01). Desflurane reduced
      the gain of vasoconstriction by a factor of three, from 2.4 to 0.8 ml.min
      1.degrees C-1 (P < 0.01). Gains, as determined by the perfusion index and laser
      Doppler flowmetry, were likewise reduced (P < 0.01). The threshold on the control
      day was only 0.2 +/- 0.1 degrees C less when significant vasoconstriction was
      defined as a flow of 0.25 ml/min rather than 1.0 ml/min. Because gain was
      reduced, however, the threshold during desflurane administration was 0.8 +/- 0.2
      degrees C less when significant vasoconstriction was defined by a flow of 0.25
      ml/min. Minimum flows were comparable and near zero with and without anesthesia.
      CONCLUSIONS: The threshold reduction (1.2 degrees C/0.4 minimum alveolar
      concentration) was similar to that observed previously during isoflurane
      anesthesia. Similarly, it is established already that maximum vasoconstriction
      intensity is comparable with and without isoflurane anesthesia. However, the data
      also indicate that even relatively low desflurane concentrations markedly reduce
      the gain of vasoconstriction. It is likely that reduced gain (i.e., slow onset of
      vasoconstriction) contributes to core hypothermia in some surgical patients.

PMID- 8533915
TI  - Inhalation toxicity study of a haloalkene degradant of sevoflurane, Compound A
      (PIFE), in Sprague-Dawley rats.
AB  - BACKGROUND: Under certain circumstances in the clinical setting, contact of the
      anesthetic sevoflurane with a CO2 absorbent (e.g., soda lime, Baralyme) leads to
      the formation of a degradant designated as pentafluoroisopropenyl fluoromethyl
      ether (PIFE; Compound A). Previous studies have shown that the kidney is the
      primary target organ for toxicity in the rat. This study was designed to
      determine the impact of PIFE on rat renal histology correlated with functional
      changes. The findings are discussed in terms of probable mechanism of action and
      relevance to humans. METHODS: Male and female Sprague-Dawley rats were exposed to
      0, 30, 61, 114, or 202 ppm PIFE for a single 3-h period via nose-only inhalation.
      Rats were observed daily for behavioral changes or external physical signs of
      toxicity (i.e., lacrimation, dyspnea, piloerection, etc.) and body weights were
      recorded at 6, 4, and 1 day preexposure and 1, 3, 7, and 13 days postexposure.
      Animals were evaluated for hematologic, clinical chemistry and/or urinalysis
      changes immediately postexposure and/or at 1, 4, and 14 days postexposure. Rats
      were killed, subjected to a macroscopic postmortem examination, and evaluated for
      histopathologic changes in all major tissues and organs at 1, 4, and 14 days
      postexposure. RESULTS: Labored breathing was observed in 3 of the 20 and 2 of the
      20 rats in the 114 ppm and 202 ppm groups, respectively, during the 3-h exposure
      period. No significant reductions in body weight gain were noted during the 2
      week study period. Clinical chemistry evaluations revealed increases in blood
      urea nitrogen and creatinine 1 day postexposure in males and females exposed to
      202 ppm PIFE. Changes in urinary glucose, protein and N-acetyl-beta
      glucoaminidase/creatinine were evident one day postexposure in males and females
      exposed to 202 ppm and in males exposed to 114 ppm PIFE. Most values were within
      normal ranges by 4 or 14 days postexposure. No drug-related alterations in
      hematologic parameters were noted. Evidence of olfactory epithelial degeneration
      and desquamation in the nasal turbinates was noted at 4 days postexposure in male
      and female rats exposed to 202 ppm PIFE. Concentration-dependent renal tubular
      necrosis and tubular cell hyperplasia, in the corticomedullary border, were
      observed in males and females exposed to 114 and 202 ppm PIFE. The severity of
      tubular necrosis in both males and females was considered minimal to slight at
      the 114 ppm exposure concentration and slight to moderate at the 202 ppm
      exposure. Both the numbers of affected animals and severity were reduced over
      time. The most marked changes in serum and urine chemistry were associated with
      the animals described as having moderate renal necrosis. Male rats appeared more
      susceptible to nephropathy than female rats. There were no other PIFE-related
      histopathologic findings. CONCLUSIONS: The renal histopathologic findings in this
      study are consistent with those reported in previous acute studies in rats after
      PIFE administration. Functional changes in the kidney, as evidenced by serum
      chemistry and urinalyses, were observed at exposure concentrations that induced
      morphologic alterations.

PMID- 8533916
TI  - Volatile and intravenous anesthetics decrease glutamate release from cortical
      brain slices during anoxia.
AB  - BACKGROUND: Extracellular accumulation of the excitatory neurotransmitter L
      glutamate during cerebral hypoxia or ischemia contributes to neuronal death.
      Anesthetics inhibit release of synaptic neurotransmitters but it is unknown if
      they alter net extrasynaptic glutamate release, which accounts for most of the
      glutamate released during hypoxia or ischemia. The purpose of this study was to
      determine if different types of anesthetics decrease hypoxia-induced glutamate
      release from rat brain slices. METHODS: Glutamate released from cortical brain
      slices was measured fluorometrically with the glutamate dehydrogenase catalyzed
      formation of the reduced form of nicotinamide adenine dinucleotide phosphate.
      Glutamate release was measured in oxygenated (PO2 = 400 mmHg), hypoxic ((PO2 = 20
      mmHg), and anoxic ((PO2 = 20 mmHg plus 100 microM NaCN) solutions and with
      clinical concentrations of anesthetics (halothane 325 microM, enflurane 680
      microM, propofol 200 microM, sodium thiopental 50 microM). The source of
      glutamate released during these stresses was defined with toxins inhibiting N and
      P type voltage-gated calcium channels, and with calcium-free medium. RESULTS:
      Glutamate released during hypoxia or anoxia was 1.5 and 5.3 times greater,
      respectively, than that evoked by depolarization with 30 mM KCl. Hypoxia/anoxia
      induced glutamate release was not mediated by synaptic voltage-gated calcium
      channels, but probably by the reversal of normal uptake mechanisms. Halothane,
      enflurane, and sodium thiopental, but not propofol, decreased hypoxia-evoked
      glutamate release by 50-70% (P < 0.05). None of the anesthetics alter basal
      glutamate release. CONCLUSIONS: The authors conclude that halothane, enflurane,
      and sodium thiopental but not propofol, at clinical concentrations, decrease
      extrasynaptic release of L-glutamate during hypoxic stress.

PMID- 8533917
TI  - Halothane modulates thermosensitive hypothalamic neurons in rat brain slices.
AB  - BACKGROUND: In vivo, halothane alters spontaneous firing in and thermosensitivity
      of neurons in the preoptic region of the anterior hypothalamus. To better
      understand the mechanisms by which halothane specifically disrupts normal
      thermoregulation, this investigation examined the effects of halothane on
      thermosensitive preoptic region neurons in isolated hypothalamic tissue slices.
      METHODS: Brain slices were obtained and prepared from Sprague-Dawley rats.
      Preoptic region neurons were characterized by extracellular recording of
      spontaneous firing rates and thermosensitivity to localized heating and cooling,
      before, during, and after halothane equilibrated in the perfusate and carrier
      gas. RESULTS: One hundred sixteen neurons were characterized by their
      thermosensitivity as: 29% warm-sensitive (> 0.8 spikes.s-1.degrees C-1); 14% cold
      sensitive (< 0.6 spikes.s-1.degrees C-1); and 57% temperature-insensitive.
      Halothane significantly reduced the spontaneous firing rates to 64% of control
      and the thermosensitivity to 55% of control for warm-sensitive neurons at 1%
      halothane. Halothane significantly reduced the spontaneous firing rate of cold
      sensitive neurons to 24 and 40% of control, and the thermosensitivity to 61 and
      36% of control at 0.5, and 1% halothane, respectively. Spontaneous firing rates
      and thermosensitivity returned toward control values in warm-sensitive neurons
      (92 and 122% of control, respectively) after discontinuation of halothane, which
      did not occur in cold-sensitive neurons (49 and 36% of control, respectively).
      Halothane did not alter the thermosensitive temperature range or the set point
      temperature at which neurons became most thermosensitive. Halothane also did not
      affect the firing rates of temperature-insensitive neurons. CONCLUSIONS:
      Halothane alters the firing rate and thermosensitivity of individual temperature
      sensitive neurons in in vitro slices of the preoptic region of the anterior
      hypothalamus in the absence of afferent modulation. This disruption may result in
      an imprecision of thermoregulatory responses locally within the preoptic region,
      to thermal challenges and represents a potential mechanism by which halothane
      widens the thermoregulatory threshold range.

PMID- 8533918
TI  - Propofol reduces neuronal transmission damage and attenuates the changes in
      calcium, potassium, and sodium during hyperthermic anoxia in the rat hippocampal
      slice.
AB  - BACKGROUND: Propofol reduces cerebral blood flow, cerebral metabolic rate for
      oxygen, and intracranial pressure and is being increasingly used in
      neuroanesthesia. In vivo studies have yielded conflicting results on its ability
      to protect against ischemic brain damage. In the current study, an in vitro model
      was used to examine the mechanism of propofol's action on anoxic neuronal
      transmission damage. METHODS: A presynaptic pathway was stimulated in the rat
      hippocampal slice to elicit a postsynaptic population spike in the CA1 region.
      The effects of propofol (20 micrograms/ml), its solvent intralipid or no drug, on
      the population spike before, during, and 60 min after anoxia at 37 degrees C or
      39 degrees C were examined. Intracellular adenosine triphosphate (ATP), Na, and K
      were measured in dissected CA1 regions at 37 degrees C and 39 degrees C after 5
      min of anoxia; 45Ca influx was measured after 10 min of anoxia. RESULTS: Propofol
      did not improve recovery after 5, 6, or 7 min of anoxia at 37 degrees C. Recovery
      of the population spike after 6 min of anoxia at 37 degrees C was 62 +/- 11% with
      propofol, 35 +/- 15% with intralipid, and 44 +/- 10% in untreated tissue (NS).
      After 5 min of anoxia at 39 degrees C, there was significantly better recovery of
      the population spike with propofol (76 +/- 12%) than with intralipid (11 +/- 6%)
      or no drug (13; +/- 5%). Propofol, but not intralipid, reduced the population
      spike amplitude before anoxia. At 37 degrees C, anoxia caused significant changes
      in ATP (62% of normoxic concentration), Ca (115%), Na (138%), and K (68%). Both
      propofol and intralipid significantly attenuated the changes in ATP (78% and 82%
      of normoxic concentration) and Ca (104% and 103%). Na changes were attenuated by
      propofol (95%) but not intralipid; K concentration was not affected by either
      drug. At 39 degrees C, for most parameters, anoxia caused more marked changes:
      ATP was 23% of normoxic concentration, Ca 116%, Na 185%, and K 48%. Both propofol
      and intralipid attenuated the decrease in ATP (56% of normoxic); propofol, but
      not intralipid, significantly attenuated the changes in Ca (100%), Na (141%), and
      K (63%). CONCLUSIONS: Propofol improved electrophysiologic recovery from anoxia
      during hyperthermia but not normothermia. At 37 degrees C propofol attenuated the
      changes in ATP, Na, and Ca, however, this did not result in improved recovery. At
      39 degrees C the changes in ATP, Na, and K caused by anoxia were greater than at
      37 degrees C; this could explain why electrophysiologic damage was worsened.
      Improved recovery with propofol at 39 degrees C may be explained by its
      attenuation of the changes in Ca, Na, and K at this temperature. The decrease in
      ATP was attenuated by both propofol and intralipid and therefore cannot explain
      the improved recovery.

PMID- 8533919
TI  - Calcium administration augments pancreatic injury and ectopic trypsinogen
      activation after temporary systemic hypotension in rats.
AB  - BACKGROUND: Calcium infusion and hypotension have been described as the most
      important risk factors for pancreatic injury after cardiopulmonary bypass.
      METHODS: Rats were randomly allocated to three experimental groups undergoing
      either sham operation and saline infusion (Control, n = 30), hemorrhagic
      reduction of mean arterial pressure to 30 mmHg for 30 min alone (hypotension, n =
      51), or hypovolemic hypotension followed by bolus infusion of CaCl2 (200 mg.kg-1;
      hypercalcemia, n = 85). Serum ionized calcium, amylase activity, trypsinogen
      activation peptide in pancreatic tissue homogenates, pancreatic wet/dry weight
      ratio, histologic changes, and mortality were assessed for 24 h. RESULTS: Control
      rats showed no significant changes of any parameter throughout the experiments.
      In contrast, hypotension significantly increased serum amylase (P < 0.001),
      tissue trypsinogen activation peptide (P < 0.01), wet/dry weight ratio (P <
      0.001), and histologic scores for edema (P < 0.001) and pancreatic necrosis (P <
      0.05). Subsequent CaCl2 administration transiently increased [Ca2+] (P < 0.001)
      with the concentration rapidly returning to baseline within 3 h. That infusion of
      CaCl2 further increased amylase (P < 0.05), tissue trypsinogen activation peptide
      (P < 0.05), wet/dry weight ratio (P < 0.001), and histologic evidence of
      pancreatic edema (P < 0.05) and acinar necrosis (P < 0.05) when compared with
      hypotension alone. Whereas all Control animals survived the experiments, 22% (P <
      0.05) and 47% (P < 0.05 vs. hypotension) of animals died in the hypotension and
      hypercalcemia groups, respectively. CONCLUSIONS: Temporary hypotension alone
      causes ectopic trypsinogen activation and lethal acute pancreatitis. Super
      imposed hypercalcemia significantly aggravates hypotension-induced pancreatic
      injury and mortality in rats.

PMID- 8533921
TI  - Cerebral vasoconstriction by indomethacin in intracranial hypertension. An
      experimental investigation in pigs.
AB  - BACKGROUND: Uncontrolled increase in intracranial pressure is the most
      significant cause of mortality in patients with severe traumatic brain lesions,
      and the efficacy of common non-surgical treatments has been questioned.
      Pharmacologically induced cerebral vasoconstriction aiming at a decrease of
      cerebral blood volume and brain edema has recently been suggested as an
      alternative. Limited clinical experience with indomethacin as a cerebral
      vasoconstrictor has been reported but dose- or concentration-effect relationships
      were not investigated. In particular, there is a lack of data showing whether a
      therapeutic window exists in which risk of cerebral ischemia is minimized.
      METHODS: In a porcine model of intracranial hypertension induced with two
      epidural balloons to a level of 26-28 mmHg, 18 animals were randomized into three
      groups receiving 0.1, 0.3, and 3.0 mg.kg-1.h-1 indomethacin, respectively, as an
      infusion during 80 min. Intracranial pressure, mean arterial blood pressure, and
      electrocortical activity were recorded continuously and measurements of cerebral
      blood flow, arteriovenous difference in oxygen content and cerebral venous pH
      were performed at 5, 20, 40, 60, and 75 min during and 10 min after the
      indomethacin infusion. Baseline measurements, performed before the indomethacin
      infusion, were used as an internal control. The infusions were
      pharmacokinetically designed to mimic the reported clinical conditions. RESULTS:
      An 11% mean decrease in intracranial pressure during the infusion, but no effects
      on cerebral blood flow, arteriovenous difference in oxygen content, venous pH,
      and electrocortical activity were observed in the group of animals receiving 0.1
      mg.kg-1.h-1. When the rate of infusion was 0.3 and 3.0 mg.kg-1.h-1, the decrease
      in intracranial pressure was 20 and 25%, respectively, but this was accompanied
      by a decrease in cerebral blood flow and venous pH, an increase in arteriovenous
      difference in oxygen content, and a slowing of the electrocortical activity. All
      changes were statistically significant. CONCLUSIONS: Indomethacin, which is known
      to constrict precapillary resistance vessels, caused a decrease in intracranial
      pressure during experimental intracranial hypertension. This was accompanied by
      signs of cerebral ischemia when indomethacin was used in a dose that has
      previously been suggested for the treatment of increased intracranial pressure in
      patients.

PMID- 8533920
TI  - Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent
      Ca2+ channels in porcine tracheal smooth muscle cells.
AB  - BACKGROUND: Intravenously administered anesthetics directly inhibit airway smooth
      muscle contraction. Because many anesthetic agents affect membrane ion channel
      function and sustained contraction of airway smooth muscle requires the influx of
      Ca2+ through voltage-dependent Ca2+ channels, it was hypothesized that
      intravenous anesthetics inhibit airway smooth muscle voltage-dependent Ca2+
      channels. METHODS: Porcine tracheal smooth muscle cells were enzymatically
      dispersed and studied using whole-cell, patch-clamp techniques. The cells were
      exposed to thiopental (10(-7)-3 x 10(-4) M), ketamine (10(-6)-10(-3) M), or
      propofol (10(-7)-3 x 10(-4) M) while recording macroscopic voltage-activated Ca2+
      currents (ICa). RESULTS: Each intravenous anesthetic tested significantly
      inhibited ICa in a dose-dependent manner with 3 x 10(-4) M thiopental, 10(-3) M
      ketamine, and 3 x 10(-4) M propofol each causing approximately 50% depression of
      peak ICa, but with no apparent shift in the voltage dependence of induced ICa.
      After pretreatment with the Ca2+ channel agonist Bay K 8644, thiopental, but not
      ketamine or propofol, shifted the maximum ICa to more positive potentials. All
      three anesthetics promoted the inactivated state of the channel at more negative
      potentials, but propofol was less effective than thiopental or ketamine in this
      regard. CONCLUSIONS: Three intravenous anesthetics evaluated in this study
      decreased the ICa of porcine tracheal smooth muscle cells but with subtle
      electrophysiologic differences. Hence, thiopental, ketamine, and propofol each
      inhibit L-type voltage-dependent Ca2+ channels of porcine tracheal smooth muscle
      cells but the molecular mechanisms involved may be agent specific. This
      inhibition may contribute to the airway smooth muscle relaxant effects of these
      agents observed in vitro at concentrations greater than those encountered
      clinically.

PMID- 8533922
TI  - Quaternary ammonium derivative of lidocaine as a long-acting local anesthetic.
AB  - BACKGROUND: Use of long-acting local anesthetics that elicit complete neural
      blockade for more than 3 h often is desirable in pain management. Unfortunately,
      clinically available local anesthetics are in general not suitable for prolonged
      analgesia. This report describes the organic synthesis and functional testing of
      a lidocaine derivative that appears to fulfill the criteria of long-acting local
      anesthetics. METHODS: A lidocaine derivative, N-beta-phenylethyl lidocaine
      quaternary ammonium bromide, was synthesized, and its ability to inhibit Na+
      currents in cultured rat neuronal GH3 cells was tested in vitro under whole-cell
      voltage clamp conditions. Neurologic evaluation of sciatic nerve block of sensory
      and motor functions in vivo was subsequently performed in rats. RESULTS: N-beta
      phenylethyl lidocaine was found to be a potent Na+ channel blocker in vitro. It
      produced both tonic and use-dependent blocks of Na+ currents that exceeded
      lidocaine's effects by a factor of > 2 (P < 0.05). In vivo, N-beta-phenylethyl
      lidocaine elicited a prolonged and complete sciatic nerve block of the motor
      function and the withdrawal response to noxious pinch that was 3.6- and 9.3-fold
      longer than that of lidocaine (P < 0.001), respectively. CONCLUSIONS: In an
      attempt to elicit prolonged local anesthesia, a quaternary ammonium derivative of
      lidocaine containing a permanent charge and an additional hydrophobic component
      was synthesized. Complete sciatic neural blockade of more than 3 h was achieved
      with this derivative. Of note, sensory blockade was prolonged to a greater extent
      than motor blockade. The approach used in this study may prove useful for
      developing new drugs applicable in pain management.

PMID- 8533923
TI  - Diaspirin cross-linked hemoglobin does not increase brain oxygen consumption
      during hypothermic cardiopulmonary bypass in rabbits.
AB  - BACKGROUND: Decreased erythrocyte deformability due to cardiopulmonary bypass
      (CPB) and/or hypothermia, may result in brain capillary beds that have decreased
      erythrocyte transit, resulting in a generalized impairment of brain oxygenation
      during CPB. Because brain capillary plasma flow continues even when erythrocyte
      flow is absent, the authors' hypothesized augmentation of plasma oxygen content
      with a non-erythrocyte-associated oxygen transport molecule would increase brain
      oxygen uptake during hypothermic CPB. METHODS: Anesthetized New Zealand white
      rabbits, maintained on CPB at 27 degrees C, were randomized to one of three
      groups. In group 1 (n = 13), plasma oxygen content was increased by
      administration of alpha-alpha diaspirin cross-linked hemoglobin. In this group,
      pretreatment with 0.5 mg/kg verapamil was necessary to prevent hypertension. In
      group 2 (n = 13), alpha-alpha diaspirin cross-linked hemoglobin was not
      administered, but verapamil was given as before (control). In group 3 (n = 13),
      neither alpha-alpha diaspirin cross-linked hemoglobin nor verapamil was
      administered (control). At 60 min of CPB, cerebral blood flow (microspheres) and
      cerebral metabolic rate for oxygen (Fick) were determined. RESULTS: Systemic
      physiologic variables did not differ among groups. Although total arterial oxygen
      content was equivalent in all groups (approximately 12.1 ml O2/dl), the alpha
      alpha diaspirin cross-linked hemoglobin group had a much greater proportion of
      the total arterial oxygen content present in a non-erythrocyte-associated form,
      29 +/- 5% versus 6 +/- 2% and 5 +/- 3%, in groups 2 and 3, respectively.
      Nevertheless, neither cerebral blood flow (approximately 34 ml.100g-1.min-1) nor
      cerebral metabolic rate for oxygen (approximately 1.2 ml O2.100g-1.min-1)
      differed among groups. CONCLUSIONS: Because oxygen was equally available to the
      brain in all groups, independent of whether oxygen was associated with
      erythrocytes or not, it was concluded that erythrocyte/capillary interactions do
      not limit oxygen transfer from blood to brain during moderately hypothermic CPB.
      The hypertensive response to alpha-alpha diaspirin cross-linked hemoglobin during
      CPB is probably a result of nitric oxide scavenging.

PMID- 8533924
TI  - Effect of propofol on spinal dorsal horn neurons. Comparison with lack of
      ketamine effects.
AB  - BACKGROUND: Pentobarbital reduces low-threshold receptive field (RF) size and
      enhances responses of some spinal dorsal horn neurons to noxious stimulation in
      cats. To better understand the effects of general anesthetics on spinal sensory
      processing, this study was designed to determine if intravenous propofol and
      ketamine have similar effects. METHODS: Spinal dorsal horn neuronal responses to
      RF stimulation were observed in physiologically intact, awake, drug-free cats.
      After baseline observations were made, the effects of propofol (7.5 or 10 mg/kg
      intravenous) or ketamine (10 mg/kg intravenous) on those neuronal responses were
      observed. RESULTS: Propofol is capable of producing a profound reduction in low
      threshold RF size. Propofol also depressed neuronal responses to non-noxious and
      noxious RF stimulation in many of the neurons tested. Ketamine was not observed
      to produce any change in either RF size or neuronal response to non-noxious RF
      stimulation. CONCLUSIONS: General anesthetics that interact with gamma
      aminobutyric acid receptors may significantly depress low-threshold sensory
      information within the spinal dorsal horn. This may contribute to anesthetic
      induced loss of sensation. Lack of a ketamine effect suggests an absence of n
      methyl-d-aspartate receptor involvement in spinal dorsal horn processing of low
      threshold sensory information.

PMID- 8533925
TI  - Vasomotor responses of rat coronary arteries to isoflurane and halothane depend
      on preexposure tone and vessel size.
AB  - BACKGROUND: The authors previously reported that in rabbits, isoflurane exhibited
      a heterogeneous vasomotor effect, constricting small resistance coronary arteries
      and dilating larger conductance arteries. The novelty of isoflurane-induced
      constriction of small coronary arteries raised the question of whether the
      finding depended on the unique experimental setup or species used. The purpose of
      this study was to address these questions. Therefore, a second species was
      studied, namely rats, as well as a second volatile anesthetic, halothane. In
      addition, the dependence of the vasomotor effect on the preexisting tone of the
      vessels was examined. METHODS: Thirty-six large coronary arteries (262 +/- 23
      microns) and 42 small coronary arteries (99 +/- 15 microns) from 31 Wistar rats
      were isolated. Each vessel was placed in a microvessel chamber and was (1)
      submaximally preconstricted with the thromboxane analog U46619; (2) submaximally
      predilated with sodium nitroprusside; or (3) neither preconstricted nor
      predilated. The vessel was then subjected to increasing concentrations of either
      isoflurane or halothane, 0-3%. Changes in inner diameter were monitored and
      recorded with optical density video detection system. RESULTS: Isoflurane
      constricted predilated or untreated small coronary arteries, but had no effect on
      preconstricted small arteries. Isoflurane dilated large coronary arteries, with
      the preconstricted vessels dilating the most. In contrast, halothane dilated both
      the small and large coronary arteries to a similar extent. Preconstricted vessels
      dilated more to halothane than vessels with no added tone. CONCLUSIONS: Whereas
      isoflurane has a heterogeneous vasomotor effect in rat coronary arteries,
      constricting the small vessels and dilating the large ones, halothane dilates
      both the small and large arteries. The vasoconstriction effect was most evident
      in vessels with no added tone, whereas the vasodilatory effect was most
      significant in preconstricted vessels.

PMID- 8533926
TI  - Metaphor and anesthesia.

PMID- 8533927
TI  - Formal instruction in difficult airway management. A survey of anesthesiology
      residency programs.
AB  - BACKGROUND: Up to 30% of all deaths attributable to anesthesia are related to
      difficulties with airway management. The purpose of this study was to determine
      whether anesthesiology residents are receiving specialized instruction in the
      various techniques and mechanical devices currently recommended for airway
      management in patients with anticipated or unanticipated difficult airways.
      METHODS: A single anonymous questionnaire about resident instruction in the area
      of difficult airway management was mailed to the directors of 169 American
      anesthesiology programs. RESULTS: Twenty-seven percent of the 143 programs from
      which there were responses require residents to participate in a rotation
      dedicated to management of the difficult airway. As they currently exist,
      rotations tend to be of short duration. Many are limited to lectures only and
      infrequently employ state-of-the-art teaching systems. In some programs,
      recognized airway management techniques such as the Bullard laryngoscope and
      esophageal-tracheal combitube are not taught at all. CONCLUSIONS: Based on the
      data obtained by the authors, formal instruction in difficult airway management
      is not offered by most residency programs. It is commonly taught as difficult
      clinical situations arise. Because these difficulties occur sporadically,
      opportunities for teaching are occasional. Learning based on sporadic and
      occasional occurrences risks incomplete and nonuniform training of residents.

PMID- 8533928
TI  - Perioperative hepatic dysfunction in two patients during elective aortic aneurysm
      repair.

PMID- 8533929
TI  - Disruption of an infrared capnograph monitor by hand-held radio transceivers.

PMID- 8533930
TI  - Paraplegia, epidural analgesia, and thoracic aneurysmectomy.

PMID- 8533931
TI  - Placement of a right atrial air aspiration catheter guided by transesophageal
      echocardiography.

PMID- 8533932
TI  - Suspected isoflurane hepatitis in an obese patient with a history of halothane
      hepatitis.

PMID- 8533933
TI  - Spinal anesthesia in an infant with epidermolysis bullosa.

PMID- 8533934
TI  - Unitary versus multiple mechanisms of anesthesia.

PMID- 8533935
TI  - Orotracheal intubation with a nasal Ring-Adair-Elwyn tube provides an
      unobstructed view in otolaryngologic procedures.

PMID- 8533936
TI  - Early French accounts of self-inhalation of ether and conscious analgesia.

PMID- 8533937
TI  - Test dose for prediction of mivacurium sensitivity in the patient with atypical
      plasma cholinesterase.

PMID- 8533938
TI  - Intravenous alcohol in 1945 and beyond.

PMID- 8533939
TI  - Reliability of auscultation of bilateral breath sounds in confirming endotracheal
      tube position.

PMID- 8533940
TI  - Simple method of tracking patients with difficult or failed tracheal intubation.

PMID- 8533941
TI  - Simple transfer of cryoprecipitate.

PMID- 8533942
TI  - Use of shoulder restraints during arm abduction and steep Trendelenburg's
      position.

PMID- 8533943
TI  - Volumetric capnography and lung growth in children: a simple model validated.

PMID- 8533944
TI  - Oral-to-nasal endotracheal tube exchange in patients with bleeding esophageal
      varices.

PMID- 8533945
TI  - Spoons to assist the insertion of the laryngeal mask airway.

PMID- 8533946
TI  - Myotonias and masseter spasm: not malignant hyperthermia?

PMID- 8533947
TI  - Detection of carbon monoxide with mass spectroscopy during anesthesia.

PMID- 8533948
TI  - Binding of halothane to serum albumin: relevance to theories of narcosis.

PMID- 8533949
TI  - Propofol and cellular calcium homeostasis.

PMID- 8533950
TI  - Comparison of estimated variable costs is a surrogate for actual cost experience.

PMID- 8533951
TI  - Nitric oxide in a premature infant in the operating room.

PMID- 8533952
TI  - Society for Obstetric Anesthesia and Perinatology. Montreal, Canada, May 17-20,
      1995.

PMID- 8533953
TI  - [Compliance of the lung-thorax system in pregnancy complicated by pre-eclampsia].
AB  - Compliance of the lungs and thorax was studied in 65 pregnant women during
      cesarean section. The measurements were carried out in a group of healthy
      controls and in patients with preeclampsia. The detected changes indicated
      increased rigidity of the lungs even in normal pregnancy. Comparison of the
      results indicates an appreciable increase of rigidity of the lungs in patients
      with preeclampsia, this permitting us to regard it as a status involving
      interstitial pulmonary hyperhydration.

PMID- 8533954
TI  - [Intensive care of respiratory insufficiency and hypoxia].
AB  - Analysis of the results of studies carried out in 1200 patients aged 1 day to 75
      years hospitalized at reanimation and intensive care wards for critical and
      terminal states of different origin showed that respiratory insufficiency and
      hypoxia play the main role in the pathogenesis of critical states and cause
      generalized disturbances of metabolism which lead to disorders in the work of
      vital organs and systems. The major part in metabolic disorders is played by
      changes in free-radical lipid peroxidation and in the system of antioxidant
      defense. An original program of "metabolic reanimation" is proposed for
      correction of the disordered metabolic processes and their aftereffects caused by
      hypoxia.

PMID- 8533955
TI  - [Prevention of ventilation hypoxia in surgical interventions on the open
      trachea].
AB  - Presents an analysis of artificial ventilation of the lungs (AVL) during
      interventions on the open trachea in 32 patients. Before crossing the trachea
      common AVL through an orotracheal tube was used. At the stage of resection of a
      portion of the trachea ventilation of one or both lungs was carried out through a
      tube inserted from the outside as shunting respiration using a method which ruled
      out additional dissection of the membranous wall of the trachea or main bronchus.
      At the stage of formation of intertracheal and tracheobronchial anastomosis AVL
      was resumed through a thin orotracheal tube moved further into the distal stump
      of the trachea or the main bronchus. High-frequency AVL through a thin
      orotracheal catheter at a frequency of 150/min provides adequate oxygenation of
      the blood and creates favorable conditions for the intervention on the open
      trachea during creating a tracheal anastomosis.

PMID- 8533956
TI  - [Effects of antioxidant therapy on the energy metabolism system and antioxidant
      defense during the acute period of myocardial infarction].
AB  - Study of the effects of antioxidant therapy on the antioxidant defense enzymes
      and mitochondrial energy metabolism in patients with acute myocardial infarction
      showed that addition of antioxidants to therapeutic protocols promoted a sooner
      stabilization of the status of the patients and shortened the periods of their
      stay in intensive care wards. Measurements of succinate dehydrogenase and
      superoxide dismutase are recommended to monitor the treatment efficacy.

PMID- 8533957
TI  - [Hyperbaric oxygenation and current methods of detoxication in multimodal
      intensive therapy of diffuse peritonitis].
AB  - The course of diffuse peritonitis has been followed up in 219 patients, 20 of
      these with the reactive, 165 with toxic, and 34 with the terminal stages of the
      condition. Multiple-modality intensive care included, besides routine therapy,
      local abdominal hypothermia, UV irradiation of autoblood (UVIAB), and, if
      indicated, hyperbaric oxygenation (HBO) and hemoperfusion. In addition to
      clinical tests, immunobiochemical monitoring of medium-molecular peptide
      fractions MM1 and MM2 and index of their distribution, as well as of circulating
      immune complexes CIC1 and CIC2 and the levels of immunoglobulins IgA, IgM, and
      IgG were the criteria for assessing the severity of intoxication and efficacy of
      intensive care and for predicting the course and outcome of the disease. The
      results indicate that HBO in combination with hemoperfusion, local abdominal
      hypothermia, and UVIAB have a positive impact on the clinical picture of the
      disease and on the time course of markers of endogenous intoxication and humoral
      immunity in patients with the terminal and toxic phases of diffuse peritonitis.

PMID- 8533958
TI  - [Role of hypoxia factor in changes of ionic composition of blood and muscle
      tissue in experimental botulinum poisoning].
AB  - Levels of sodium and potassium ions in muscle tissue, blood plasma and red cells
      were measured, and the index characterizing the capacity of tissue to accumulate
      cations from the environment and the discrimination coefficient were calculated
      in experiments on white rats subjected to experimental generalized botulinum
      poisoning. Late stages of botulism were found to involve a deficit of potassium
      and sodium ions in red cells. With the progress of intoxication, a deficit of
      potassium ions develops in muscle tissue and the capacity of this tissue to
      accumulate potassium ions from the environment declines. All these disorders are
      more expressed in rapidly contracting skeletal muscles. An antihypoxant gutimin
      reduces sodium deficit in the blood plasma and red cells and leads to
      normalization of potassium ion levels in muscle tissue.

PMID- 8533959
TI  - [Significance of the energetic value of respiration in the assessment of the
      degree of strain of compensatory mechanisms in respiratory insufficiency].
AB  - A total of 170 examinations of the external respiration function were carried out
      in 114 patients with postoperative respiratory insufficiency (RI). The patients
      were examined during air respiration (FiO2 0.21). Pulmonary function was computer
      monitored. Thirty-four parameters were analyzed, which characterize pulmonary
      ventilation, gas exchange, respiratory mechanics, and metabolism. Three groups of
      patients were distinguished: with moderate, expressed, and maximal stages of
      energy compensation of RI. Augmentation of RI in the course of the postoperative
      period was found to be characterized by reduction of lung compliance and increase
      of aerodynamic resistance of the airways and specific and minute Decompensation
      of RI develops due to fatigue of the respiratory muscles under conditions of
      increased energy value of respiration, which is proved by the appearance of a
      reliable inverse correlation between the minute respiratory volume and increased
      inhalation and exhalation resistance and between respiratory volume and increased
      inhalation resistance and of a direct correlation between respiratory volume and
      lung compliance in patients during the maximal energy compensation of respiratory
      insufficiency. Hence, the energy value of respiration objectively reflects the
      strain of the compensatory mechanisms during respiratory insufficiency.

PMID- 8533960
TI  - [Acute respiratory failure as the 1st symptom of migration of a central venous
      catheter into the mediastinum].
AB  - Reports a case with late development of hydromediastinum and right-side
      hydrothorax as a result of migration of the central venous catheter into the
      mediastinum. Acute respiratory insufficiency was the first symptom of this
      complication.

PMID- 8533961
TI  - [Metabolic components of anesthesiological provision in surgery of suppurative
      inflammatory diseases of the abdominal cavity].
AB  - The authors analyze the experience gained with the use of multicomponent
      intravenous anesthesia and epidural anesthesia in combination with a synthetic
      opioid dalargin, protease inhibitor trasylol, and sulfhydryl group donor
      unithiol. The studies were carried out in 164 patients operated on for
      pyoinflammatory diseases of the abdominal and small pelvis organs. Under study
      were the parameters of central hemodynamics, oxygen-transporting system, and
      lipid peroxidation. Use of the before-said metabolic components of anesthesia
      promoted an appreciable reduction of fentanyl and lidocaine doses (almost five-
      and twofold, respectively) with an adequate antistress defense being the same,
      hemodynamics and oxygen transport stabilized, and a membrane protective effect
      observed.

PMID- 8533962
TI  - [Changes in the ratio of formed elements of the blood in acute exogenous
      poisoning in children].
AB  - In order to estimate the informative value of the leukocytic index of
      intoxication and the neutrophil to lymphocyte ratio in the assessment of the
      status of children with acute poisonings, the authors analyzed 223 hemograms of
      189 children aged 1 to 15 with different types of acute poisonings. The results
      indicate that these parameters are nonspecific, their values depend on the
      severity of the patient's status and are unrelated to sex, age, and type of
      poisoning; a correlation between the concentration of the toxic agent in the
      blood and hemogram parameters has been confirmed.

PMID- 8533963
TI  - [Hemosorption in the treatment of patients with severe forms of chronic arterial
      insufficiency of the lower limbs].

PMID- 8533964
TI  - [Ketamine-clofelin anesthesia in children].
AB  - Changes in the activity of the main antiradical enzymes of the blood serum-
      superoxide dismutase (SOD) and catalase (C), red cell peroxide resistance (RCPR),
      accumulation of the intermediate and end products of free-radical lipid
      peroxidation (FR LPO)--diene conjugates (DC) and malonic dialdehyde (MDA)--were
      studied in children subjected to different types of anesthesia. Ketamine in
      combination with clofelin helped reduce the activity of FR LPO. This was
      confirmed by the minimal changes in the activities of SOD, C, and RCPR, and the
      lowest level of accumulation of DC and MDA in children operated on under ketamine
      clofelin narcosis.

PMID- 8533965
TI  - [Clinico-pharmacological approaches to the use of lasix].

PMID- 8533966
TI  - [Hypophosphatemia: etiology, pathogenesis, clinical manifestations and
      treatment].

PMID- 8533968
TI  - [Intensive care of patients with embolism of the pulmonary artery].

PMID- 8533967
TI  - [Intensive therapy of respiratory insufficiency in status asthmaticus].

PMID- 8533969
TI  - [Acute respiratory insufficiency in hemoblastoses: evaluation of treatment
      effectiveness by survival rate].
AB  - Acute respiratory failure (ARF) is a typical complication of chemotherapy for
      hematologic malignancies. Despite the effective correction of gas exchange by
      mechanical ventilation, the mortality in this population is expected to be
      extremely high due to unavoidable fatal infection of immunocompromised host and
      the poor prognosis of primary malignancy. However, modern specific treatment of
      leukemia and lymphoma has made these conditions curable in many cases, and even
      severe myelotoxic neutropenia does not always lead to uniformly fatal outcome. We
      studied survival in 113 cases of ARF retrospectively selected according to the
      uniform criteria of this syndrome. No selection was made as to the diagnosis,
      stage, and response to the treatment of the underlying disease. The group
      consisted of 51% male and 49% female patients aged 34, on an average; 69% of
      these with acute leukemia, 22% with malignant lymphoma, and 9% with other
      conditions. Sixty-five (58%) patients were subjected to mechanical ventilation
      (MV). Forty-two were treated after a Protocol on intensive care of ARF which
      contained standard requirements to management of patients. Another group of 71
      patients admitted to intensive care units before this Protocol was introduced
      were historical controls. Total survival was 19.5%. In the MV group survival was
      15% with 10 cases of cure, ARF developing during severe neutropenia in 3 out of
      these 10 cases. The results became evidently better after the Protocol was
      introduced, improving from 16 to 27%. The primary disease dramatically influenced
      the results: long-term survival was significantly poorer in patients with
      relapses and resistant to chemotherapy, with 100% mortality within 8 months after
      discharge. A conclusion is drawn that intensive care of ARF including MV is
      justified in patients with hematologic malignancies, except cases when primary
      malignancy is not properly treated or resistant to specific chemotherapy.

PMID- 8533970
TI  - In vitro modulation of bovine blood neutrophils and mononuclear cells by
      oxytetracycline.
AB  - The effect of oxytetracycline (OTC) on bovine blood mononuclear cells and
      neutrophil functions was examined in vitro. Neutrophil functions tested include
      respiratory burst, peroxidase, and antibacterial activities. Neutrophils were
      treated with OTC (10 to 1,500 micrograms/ml) before exposure to either opsonized
      zymosan or bacteria. A dose-response inhibition of antibacterial activity to high
      concentrations of OTC (500 to 1,000 micrograms/ml) was observed. Beginning at a
      concentration of 15 micrograms/ml, OTC treatment of neutrophil lysates resulted
      in decreased peroxidase activity. A dose response was not observed. In contrast,
      respiratory burst, measured by nitroblue tetrazolium dye reduction, increased
      after OTC exposure, but only at high concentrations (500 and 1,000 micrograms/ml)
      of OTC. Mitogen-induced proliferation of blood mononuclear cells cocultured with
      OTC and concanavalin A, phytohemagglutinin-P, or pokeweed mitogen was inhibited
      at an OTC concentration of 100 micrograms/ml at 48 and 72 hours of culture. These
      results indicate that blood mononuclear cells are more sensitive to the
      inhibitory effects of OTC than are neutrophils. Furthermore, the OTC-mediated
      inhibition of neutrophil antimicrobial activity is inversely related to the
      increase in nitroblue tetrazolium reduction. This suggests that OTC is uncoupling
      the hexose monophosphate shunt from production of secreted oxygen radicals. These
      results also suggest that the peroxidase enzyme system has a large biological
      reserve capacity.

PMID- 8533971
TI  - Tumor necrosis factor-alpha production in swine after oral or respiratory
      challenge exposure with live Salmonella typhimurium or Salmonella choleraesuis.
AB  - A series of experiments was conducted to document tumor necrosis factor-alpha
      (TNF) activity in serum of swine after inoculation with Salmonella spp endotoxin
      and after oral or respiratory tract challenge exposure with live Salmonella spp.
      For experiment 1, a potentially lethal dose of S typhimurium endotoxin (25
      micrograms/kg of body weight) was administered IV, and serum TNF activity was
      measured. High TNF (approx 700 IU/ml) activity at 1 to 2 hours after
      administration of the inoculum was associated with death, whereas lower TNF
      (approx 30 IU/ml) activity was associated with a general prolonged state of
      shock. For experiment 2, pigs were administered a nonlethal dose (5
      micrograms/kg, IV) of either S typhimurium or S choleraesuis endotoxin.
      Difference in the ability to induce porcine serum TNF activity was not observed
      between strains. During experiment 3, pigs were inoculated with 10(4) colony
      forming units of S typhimurium chi 4232 either orally by gelatin capsule (GC) or
      by intranasal (IN) instillation. A late serum TNF response (17 IU/ml) was
      measured at 6 weeks after IN inoculation. A serum TNF response was not detected
      in GC-inoculated pigs. All tissues and feces were test-negative for S typhimurium
      prior to the 6-week TNF response. Serum TNF activity may be related to clearance
      of S typhimurium after respiratory tract exposure, but it is not important to or
      indicative of clearance of orally presented S typhimurium in swine. During
      experiment 4, pigs were inoculated with 10(6) colony-forming units of S
      typhimurium chi 4232 similarly as for experiment 3.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8533972
TI  - Persistence of a single electropherotype and serotype (G6P5) of bovine rotavirus
      in calves on a closed dairy farm from 1990 to 1993.
AB  - A virologic survey was conducted on calves with diarrhea associated with bovine
      rotavirus (BRV) on a closed dairy farm. The BRV was detected from 32 of 219
      (14.6%) fecal specimens repeatedly collected from 56 calves born during the years
      1992-1993, regardless of whether they had diarrhea. Most of the 32 strains were
      isolated from fecal specimens obtained from 2- to 6-week-old calves. After
      electrophoresis of double-stranded viral RNA from the 32 strains, genomic RNA
      migration patterns were similar to those of the predominant BRV strains isolated
      at the same farm during the years 1990-1991. All representative strains were
      identified as G serotype 6 (G6) and P type 5 (P5) by results of the virus
      neutralization test and polymerase chain reaction procedure. Thus, BRV had no
      change in genomic RNA electropherotypes and serologic antigenicities in a closed
      dairy herd over a period of several years.

PMID- 8533973
TI  - Efficacy of a variety of disinfectants against Actinobacillus pleuropneumoniae
      serotype 1.
AB  - The efficacy of 23 disinfectants (including the most commonly used chemical
      groups) and 6 quaternary ammonium compound based commercial formulations against
      Actinobacillus pleuropneumoniae serotype 1 (ATCC 4074) was studied. The organisms
      were tested in suspension and carrier tests with serum as the organic matter.
      Chloramine-T, hydrogen peroxide, glutaraldehyde, and mercurochrome alone, and a
      quaternary ammonium compound formulation containing 10% benzalkonium chloride,
      2.5% glutaraldehyde, 6.8% glyoxal, and 6% formaldehyde were effective in all
      tests, regardless of the presence or absence of organic load. All but 2 of the
      nonformulated disinfectants (sodium hypochlorite and an iodophor) caused at least
      a 3-log10 reduction in colony-forming units in the suspension test. However, most
      of the disinfectants were not as effective in the carrier test as in the
      suspension test; this difference ranged from a 1- to 5-log10 reduction in colony
      forming units. In addition, the presence of serum considerably reduced the
      disinfectant capacities of most of the compounds tested, particularly in the
      carrier test. These results indicate the importance of selecting suitable
      disinfectants for routine use on surfaces contaminated with this organism,
      especially in the presence of organic matter. Chloramine-T and the aforementioned
      commercial formulation were also tested directly under field conditions in pig
      nurseries, confirming their high effectiveness.

PMID- 8533974
TI  - Sensitivity and specificity of various serologic tests for detection of
      Toxoplasma gondii infection in naturally infected sows.
AB  - The sensitivity and specificity of various serologic tests for antibodies to
      Toxoplasma gondii were compared in 1,000 naturally exposed sows, using isolation
      of viable T gondii as the definitive test. Serum samples obtained from heart
      blood of 1,000 sows from Iowa were examined for T gondii antibodies by use of the
      modified agglutination test (MAT), latex agglutination test (LAT), indirect
      hemagglutination test (IHAT), and ELISA. Toxoplasma gondii was isolated from 170
      hearts of 1,000 sows by bioassays in mice and cats. The percentage of samples
      diagnosed as positive for each of the serologic tests was: MAT = 22.2% (titer >
      or = 1:20), IHAT = 6.4% (titer > or = 1:64), LAT = 10.4% (titer > or = 1:64), and
      ELISA = 24.1% (OD > 0.360). The sensitivity and specificity of these tests were
      calculated respectively to be: 82.9 and 90.29% for MAT, 29.4 and 98.3% for IHAT,
      45.9 and 96.9% for LAT, and 72.9 and 85.9% for ELISA. The dye test was run at
      1:20 dilution on only 893 sera because of bacterial contamination and presence of
      anticomplement substances. Dye test antibodies were found in 17.8% of the sera,
      and sensitivity and specificity were 54.4 and 90.8%, respectively. Thus, the MAT
      had the highest sensitivity among all serologic tests used.

PMID- 8533975
TI  - Trypanosoma cruzi infection in Walker hounds from Virginia.
AB  - Trypanosomiasis has been reported in dogs from Texas, Oklahoma, Louisiana, and
      South Carolina. We describe the first isolation and characterization of
      Trypanosoma cruzi from a Walker Hound pup in Virginia that also had postvaccinal
      distemper. The mother of the pup and 7 of its 8 siblings also were found to be
      infected with T cruzi, suggesting that the parasite had been transmitted
      transplacentally or through lactation. Parasitologic, serologic, histologic, and
      molecular methods were used to establish the diagnosis of T cruzi infection in
      these dogs. In a serologic survey of 12 dogs (including the sire of the pups)
      from the area in which the index case occurred, none were found to have
      antibodies to T cruzi. However, 2 of a further 52 dogs from different areas (to
      the index case), but in the same county, were seropositive to T cruzi. These
      findings indicate that canine trypanosomiasis is present in an area of the United
      States not previously known to be enzootic.

PMID- 8533976
TI  - Definition of chemiluminescence and superoxide production responses of bovine
      neutrophils to selected soluble and particulate stimulants, and comparisons with
      the responses to Pasteurella haemolytica.
AB  - We defined methods for use of luminol-dependent chemiluminescence (LDCL) and
      superoxide anion (O2-) production as parameters of the oxidative metabolism of
      neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how
      variations in blood sample handling, agonist preparation, individual variability,
      and age of calves influenced the LDCL and O2- responses to certain agonists, and
      defined concentrations of soluble and particulate agonists that maximally
      stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses,
      particularly LDCL, were characterized by marked day-to-day variability, differed
      greatly within and between calves, were partially age-dependent, and were
      partially dependent on the individual agonist. Superoxide anion production had
      substantially less variability. We compared the in vitro oxidative (LDCL and O2-)
      responses of neutrophils isolated from neonatal calves stimulated by defined
      concentrations of the agonists--latex, phorbol myristate acetate, calcium
      ionophore, and opsonized zymosan--with responses to formylated oligopeptides and
      zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized
      Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or
      nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils
      although P haemolytica was a less potent stimulant of oxidative functions than
      were nonbiological agonists. We conclude that the generation of reactive oxygen
      species by bovine neutrophils in response to P haemolytica is highly dependent on
      the presence of opsonins and is greatly enhanced in live vs killed bacteria.
      Furthermore, the in vitro generation of reactive oxygen species, including O2- by
      stimulated neutrophils, may be of biologic importance if similar events occur in
      vivo, and could have a major role in the pathogenesis of the acute lung injury
      associated with pneumonic pasteurellosis.

PMID- 8533977
TI  - Enzyme release by bovine neutrophils.
AB  - Release of enzymes from cytoplasmic granules has been postulated to have a major
      role in neutrophil-mediated tissue injury. Secretion or release of primary
      granules, specific granules, and cytosolic enzymes by bovine neutrophils was
      examined by quantifying the release of beta-glucuronidase, B12-binding protein,
      and lactate dehydrogenase, respectively, in response to predetermined amounts of
      phorbol myristate acetate, calcium ionophore, and opsonized zymosan. These
      responses were compared with the enzyme release induced by exposure to live or
      dead, unopsonized or opsonized Pasteurella haemolytica. The greatest release of
      beta-glucuronidase, B12-binding protein, and lactate dehydrogenase was observed
      in neutrophils exposed to live organisms partially because of neutrophil lysis.
      Bovine neutrophils respond markedly to particulate agonists, live or dead,
      pathogenic or nonpathogenic, by a selective release of specific granules, an
      effect enhanced by opsonization. Particulate agonists induce minimal primary
      granule release other than that induced by cell death. Because bovine neutrophils
      contain quantitatively high numbers of specific granules, the high rate of
      secretion/release in response to P haemolytica organisms could have a major role
      in the tissue responses that characterize the lesions of pneumonic
      pasteurellosis.

PMID- 8533978
TI  - Cultured pig rhabdomyosarcoma cells with a deletion of the Xq24-qter chromosome
      region: an immunochemical and cytogenetic characterization.
AB  - A pig rhabdomyosarcoma cell line (PRUM59) was established, and the
      immuno(histo)chemical and cytogenetic characterization of these cells was
      determined. At various swine farms in the Netherlands, pigs were observed that
      had solitary or multiple skin nodules, which were diagnosed as rhabdomyosarcomas.
      Cells of a tumor derived from a 3.5-week-old female pig were cultured for
      immunochemical and cytogenetic analyses. The cell line had characteristic
      features of undifferentiated muscle cells, similar to those observed in tumor
      tissue sections; they contained titin, a high-molecular weight protein specific
      for striated muscle, as dot-like aggregates and as filaments, desmin filaments
      and cross-striations, smooth muscle actin stress fibers, and vimentin filaments.
      The cells stained positively for striated muscle actin and tropomyosin as well.
      The immunohistochemical staining results were supported by results of
      immunoblotting experiments. Karyotyping of the cells revealed a deletion of a
      major part of Xq24-qter, a part of the long arm of 1 of the 2 X chromosomes. The
      other X chromosome and all autosomes appeared to be normal.

PMID- 8533979
TI  - Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein
      lipase activity and coagulation in healthy horses.
AB  - We evaluated the pharmacokinetics of IV administered sodium heparin and the
      pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses
      were allotted to 3 groups. Plasma samples were obtained from each horse before
      and at various times for 6 hours after heparin administration for determination
      of heparin concentration, LPL activity, and activated partial thromboplastin time
      (APTT). The disposition of heparin was dose dependent. The area under the plasma
      heparin concentration vs time curve (AUC) increased more than proportionally with
      dose, indicating that heparin elimination was nonlinear. Total clearance of
      heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging
      0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120
      IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose.
      The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120
      IU/kg, respectively, with significant differences observed between the low and
      high doses. In contrast to heparin, the area under the plasma concentration vs
      time curve for LPL activity increased less than proportionally with dose. Maximal
      LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty
      acids/ml/h. The APTT was significantly prolonged for 120 minutes after
      administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs
      either plasma heparin concentration or APTT were less than 0.7, indicating that
      neither laboratory measure can be used to accurately predict plasma LPL activity.

PMID- 8533980
TI  - Plasma and synovial fluid kinetics, disposition, and urinary excretion of
      naproxen in horses.
AB  - Naproxen (+6-methoxy-[alpha-methyl]-2-naphthalene acetic acid) is a nonsteroidal
      anti-inflammatory drug that is used for the treatment of inflammatory conditions
      in horses. We developed a model that describes the drug's disposition and renal
      excretion, including synovial fluid disposition and elimination after IV
      administration in horses. The plasma disposition, after IV administration of 5
      mg/kg of body weight, was described by a two-compartment model; mean +/- SD
      distribution and elimination half-lives were 1.42 +/- 0.42 and 8.26 +/- 2.56
      hours, respectively. Plasma concentration of naproxen after IV administration of
      5 mg/kg was 55.3 +/- 13.5 and 0.61 +/- 0.42 mg/L at 5 minutes and 48 hours after
      its administration, respectively. Steady-state volume of distribution was 0.163
      +/- 0.053 L/kg, and area under the plasma concentration time-curve was 372.1 +/-
      128.2 mg/h/L. The peak synovial fluid concentration of 12.68 +/- 12.39 mg/L was
      measured at 6 hours, and decreased to 0.71 +/- 0.38 mg/L at 36 hours after
      naproxen administration. The decrease of naproxen concentration in synovial fluid
      paralleled that in plasma. The appearance half-life of naproxen in synovial fluid
      was 4.64 hours, and the elimination half-life was 6.73 hours. Total body
      clearance was 0.015 +/- 0.006 L/h/kg. The percentage of plasma protein binding
      was 97.0 +/- 2.9% at plasma concentrations between 5 and 100 mg/L. This was
      significantly (P < 0.05) higher than the percentage of binding at plasma
      concentrations of 0.5, 1, and 500 mg/L, which was 75.2 +/- 11.8%. Most of the
      drug was excreted as glucuronidated naproxen and unconjugated
      desmethylnaproxen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533981
TI  - Effect of bethanechol, neostigmine, metoclopramide, and propranolol on
      myoelectric activity of the ileocecocolic area in cows.
AB  - The effect of bethanechol, neostigmine, metoclopramide, and propranolol on
      myoelectric activity of the ileum, cecum, and proximal loop of the ascending
      colon was determined in 6 healthy Jersey cows implanted with 8 pairs of bipolar
      electrodes. Assigned at random, each cow received each of 5 treatments in 3-day
      intervals. The treatments included bethanechol (0.07 mg/kg of body weight, SC),
      neostigmine (0.02 mg/kg, SC), metoclopramide (0.15 mg/kg, IM), DL-propranolol
      (0.2 mg/kg, IM), and 0.9% sodium chloride (NaCl) solution (20 ml, SC). All drugs
      were administered during early phase I of the migrating myoelectric complex in
      the ileum. Myoelectric activity was recorded for 4 hours after treatment, and
      data were analyzed for each hour separately. Bethanechol and neostigmine
      significantly (P < 0.05) increased the number of cecocolic spikes per minute per
      electrode, duration of cecocolic spike activity (%), and number of cecocolic
      propagated spike sequences per 10 minutes, relative to NaCl, during 1 or more
      hours of the recording period. The effect of bethanechol was more pronounced on
      duration of spike activity and number of propagated spike sequences, whereas
      neostigmine mainly increased the number of (uncoordinated) spikes. Metoclopramide
      and propranolol had no significant effect on cecocolic myoelectric activity,
      relative to NaCl. It was concluded that bethanechol and, less likely, neostigmine
      at the dosage used in this study may be suitable for medical treatment of cecal
      dilatation in cattle in which hypomotility of the cecum and proximal loop of the
      ascending colon has to be reversed. The potential advantage of bethanechol vs
      neostigmine for medical treatment of cecal dilatation is worth further
      evaluation.

PMID- 8533982
TI  - Bupivacaine disposition and pharmacologic effects after intravenous and epidural
      administrations in dogs.
AB  - Pharmacokinetic variables of bupivacaine (BPV) were determined after IV and
      epidural administrations in the same 6 dogs. Plasma BPV concentration curves
      after IV administration were adjusted to biexponential kinetics: a rapid
      distribution phase was followed by a slower elimination phase, with half-life of
      34.5 +/- 7.8 minutes. Mean plasma clearance was 20.2 +/- 7.4 ml/min/kg of body
      weight, and mean volume of distribution at steady state was 0.7 +/- 0.2 L/kg.
      After epidural administration, absorption was rapid. Peak plasma concentration,
      1.4 +/- 0.4 microgram/ml, was detected approximately 5 minutes after BPV
      administration. The half-life corresponding to epidural administration (179 +/-
      33.6 minutes) was 5 to 6 times longer than that observed after IV administration,
      possibly because of the slow release of BPV from the epidural space. Induction
      times were short (2.3 +/- 2.2 minutes); anesthesia quickly began and lasted for
      more than 2 hours (158 +/- 48.8 minutes). During that period, BPV plasma
      concentration ranged between 1.4 and 0.2 microgram/ml. Changes in systolic blood
      pressure and heart rate were correlated to high plasma concentration of BPV.
      These modifications were observed for the first 30 minutes, reaching baseline
      values after 60 minutes.

PMID- 8533983
TI  - Subcellular biochemical changes during the development of the small intestine of
      pony foals.
AB  - To examine the postnatal development of equine small intestine, biopsy specimens
      of jejunal mucosa from 8 ponies, between 6 and 28 weeks old, were subjected to
      analytical subcellular fractionation and assay of organelle marker enzymes.
      Fractionation revealed a reduction in the particulate brush border component of
      beta-galactosidase (lactase) activity between 6 and 28 weeks, and a corresponding
      increase in soluble activity, although the reduction in mean specific activity
      was not significant. There also was a decrease in the proportion of brush border
      to soluble aminopeptidase N activity, a relative loss of brush border gamma
      glutamyltransferase activity, and a considerable decrease in the specific
      activity of alkaline phosphatase throughout the gradient fractions. In contrast,
      there were marked increases in activities of alpha-glucosidase (maltase) and
      sucrase in the older ponies, accompanied by considerable changes in the
      intracellular distribution of particulate alpha-glucosidase activity, which was
      predominantly associated with endoplasmic reticulum at 6 weeks, whereas the large
      increase in activity observed by 28 weeks was clearly associated with the brush
      border. The modal density of brush borders also increased with age, suggestive of
      an increase in the glycoprotein-to-lipid ratio of the microvillar membrane. In
      contrast to these brush border changes, there was relatively little alteration in
      the activities or density distributions of marker enzymes for endoplasmic
      reticulum, basolateral membranes, mitochondria, or lysosomes. These findings
      indicate that maturation of equine intestinal epithelium during the first few
      months of life results in major changes in the properties and enzyme composition
      of enterocyte brush borders.

PMID- 8533984
TI  - Evaluation of pulmonary function and analgesia in dogs after intercostal
      thoracotomy and use of morphine administered intramuscularly or intrapleurally
      and bupivacaine administered intrapleurally.
AB  - Eighteen dogs undergoing lateral thoracotomy at the left fifth intercostal space
      were randomly assigned to 1 of 3 postoperative analgesic treatment groups of 6
      dogs each as follows: group A, morphine, 1.0 mg/kg of body weight, IM; group B,
      0.5% bupivacaine, 1.5 mg/kg given interpleurally; and group C, morphine, 1.0
      mg/kg given interpleurally. Heart rate, respiratory rate, arterial blood
      pressure, arterial blood gas tensions, alveolar-arterial oxygen differences,
      rectal temperature, pain score, and pulmonary mechanics were recorded hourly for
      the first 8 hours after surgery, and at postoperative hours 12, 24, and 48. These
      values were compared with preoperative (control) values for each dog. Serum
      morphine and cortisol concentrations were measured at 10, 20, and 30 minutes,
      hours 1 to 8, and 12 hours after treatment administration. All dogs had
      significant decreases in pHa, PaO2, and oxygen saturation of hemoglobin, and
      significant increases in PaCO2 and alveolar-arterial oxygen differences in the
      postoperative period, but these changes were less severe in group-B dogs.
      Decreases of 50% in lung compliance, and increases of 100 to 200% in work of
      breathing and of 185 to 383% in pulmonary resistance were observed in all dogs
      after surgery. Increases in work of breathing were lower, and returned to
      preoperative values earlier in group-B dogs. The inspiratory time-to-total
      respiratory time ratio was significantly higher in group-B dogs during
      postoperative hours 5 to 8, suggesting improved analgesia. Blood pressure was
      significantly lower in group-A dogs for the postoperative hour. Significant
      decreases in rectal temperature were observed in all dogs after surgery, and
      hypothermia was prolonged in dogs of groups A and C. Significant differences in
      pain score were not observed between treatment groups. Cortisol concentration was
      high in all dogs after anesthesia and surgery, and was significantly increased in
      group-B dogs at hours 4 and 8. Significant differences in serum morphine
      concentration between groups A and C were only observed 10 minutes after
      treatment administration. In general, significant differences in physiologic
      variables between groups A and C were not observed. Results of the study indicate
      that the anesthesia and thoracotomy are associated with significant alterations
      in pulmonary function and lung mechanics. Interpleurally administered bupivacaine
      appears to be associated with fewer blood gas alterations and earlier return to
      normal of certain pulmonary function values. Interpleural administration of
      morphine does not appear to provide any advantages, in terms of analgesia or
      pulmonary function, compared with its IM administration.

PMID- 8533985
TI  - Enzymatic analysis of liver samples from rainbow trout for diagnosis of blue
      green algae-induced toxicosis.
AB  - Microcystin and related toxic peptides produced by cyanobacteria (blue-green
      algae) are potent and selective inhibitors of protein phosphatases 1 and 2A. We
      adapted existing enzymatic techniques to analyze the liver of rainbow trout after
      oral administration of hepatotoxic cyanobacteria. Liver tissue was removed 3 and
      12 hours after treatment, and phosphatase activity was determined in liver
      extracts, using a specific phosphoprotein substrate. In all samples from fish
      exposed to toxic cyanobacteria, phosphatase activity was suppressed, whereas the
      control enzyme, lactate dehydrogenase, present in the same liver extract, was not
      affected by cyanobacteria. Thus, experimental poisoning by hepatotoxic
      cyanobacteria resulted in an abnormally low ratio of phosphatase to lactate
      dehydrogenase activity in the liver extracts. These results indicate that
      specific inhibition of phosphatases 1 and 2A may provide a useful diagnostic tool
      to determine the early effects of cyanobacteria toxic peptides directly in liver
      samples from poisoned animals. Although this test was developed with rainbow
      trout, it should be possible to extend the analysis of liver phosphatase activity
      to other species, including sheep and cattle, which are frequently affected by
      hepatotoxic cyanobacteria.

PMID- 8533986
TI  - Comparative analyses of peritoneal fluid from calves and adult cattle.
AB  - Reference values for hematologic variables change with increasing age in cattle.
      Therefore, the purpose of the study reported here was to describe the peritoneal
      fluid constituents of clinically normal young calves, and to compare cellular
      concentration and distribution in blood and peritoneal fluid of young calves with
      those of adult cattle. Eight healthy 8-week-old male Holstein calves and 8
      healthy 3- to 8-year-old Holstein cows were studied. Peritoneal fluid was
      collected from calves along the ventral midline, 4-cm cranial to the umbilicus.
      Abdominocentesis was performed in the region of the lower right flank in adult
      cattle. Correlation analysis, using the Pearson's correlation coefficient, and
      regression analysis were performed for blood and peritoneal fluid data from
      calves. Data from calves were compared with those of cows, using Wilcoxon's rank
      sum test. A P value < 0.05 was considered significant for all tests. Calves had
      significantly lower blood eosinophil count (P < 0.003) and plasma protein
      concentration (P < 0.001) than did cows. Calves had significantly higher
      peritoneal fluid nucleated cell (P < 0.05) and mononuclear cell (P < 0.05)
      counts, but lower peritoneal fluid eosinophil cell count (P < 0.003) than did
      cows. For calves, nucleated cell and lymphocyte cell counts in the blood had a
      high, positive correlation with those of peritoneal fluid. However, the
      prediction equation for nucleated cell count accounted for a modest proportion of
      variability. A prediction equation for peritoneal fluid lymphocyte cell count was
      established.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533987
TI  - Noninvasive detection of nonsteroidal anti-inflammatory drug-induced gastropathy
      in dogs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) are widely used for treatment of
      people and animals. Their use is limited by frequent side effects commonly
      involving the gastrointestinal tract, most important of which is development of
      ulcerating lesions principally in the stomach. Unfortunately, presence of such
      lesions is often unsuspected because clinical signs may be overlooked until a
      complication develops. We reported that such damage can be detected by measuring
      the increase in gastric permeability that is a hallmark of this condition.
      Sucrose is a novel probe molecule for determination of site-specific gastric
      permeability. As a disaccharide, it is large enough to be effectively excluded by
      the intact gastric epithelium, and because it is rapidly digested within the
      small intestine, absorption of the intact molecule implies damage proximal to
      this site. Recently, we found that increased sucrose permeability is useful in
      predicting presence of endoscopically relevant gastric damage in people. We
      extended these results to the detection of NSAID-induced gastropathy in dogs.
      Dogs treated with aspirin developed NSAID-induced gastropathy (including gastric
      ulceration), and the degree of endoscopically detectable damage correlated well
      with sucrose permeability. Furthermore, healing of these lesions could also be
      monitored by sequential measurements of sucrose permeability. Sucrose
      permeability decreased more rapidly than the disappearance of gastric ulcers,
      suggesting that this technique is more sensitive to generalized mucosal damage
      than is the presence of discrete, endoscopically visible ulceration. This was
      confirmed by creating artificial ulcers in the antrum and observing that sucrose
      permeability was not increased in the setting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8533988
TI  - New approach to percutaneous muscle biopsy in dogs.
AB  - The size and quality of muscle specimens obtained by use of a percutaneous biopsy
      technique were studied. All biopsies were performed under local anesthesia, using
      an 11-gauge biopsy needle. The mean +/- SEM size of specimens obtained from 128
      biopsies of the semitendinosus muscles of 16 Alaskan Huskies was 23.8 +/- 4.4 mg.
      All biopsy specimens were of sufficient quality to permit histochemical
      differentiation of the fiber types by use of myosin ATPase staining. An
      additional 8 biopsy specimens were obtained from 1 dog and analyzed for muscle
      glycogen content. These specimens contained 50.6 +/- 7.2 mmol of glucose/kg of
      muscle wet weight. This modified biopsy procedure was free of notable
      complications, and repeatable use produced specimens of adequate size and quality
      for histologic and biochemical analysis. It is concluded that this procedure is a
      safe and reliable alternative to open biopsy for diagnosis and management of
      neuromuscular, metabolic, and nutritional myopathies.

PMID- 8533989
TI  - Prothrombotic events in the prodromal stages of acute laminitis in horses.
AB  - Prothrombotic changes occurring in the prodromal stages of carbohydrate-induced
      laminitis were investigated. Hemostatic alterations were evaluated by determining
      platelet counts, platelet survival, activated partial thromboplastin time, one
      stage prothrombin time, and monocyte procoagulant activity. Thrombosis of vessels
      in the hoof wall was evaluated by contrast arteriography and histologic
      examination. Of 5 horses, 4 became lame between 28 and 52 hours after
      carbohydrate administration. Mean platelet count in laminitis-affected horses was
      lower throughout the prodromal stages of laminitis, compared with that in control
      horses, but differences were not statistically significant. However, survival of
      indium-111-labeled platelets was less than the value in control horses by 6 hours
      after carbohydrate administration. Arteriography of disarticulated feet revealed
      marked reduction in blood supply to hooves in laminitis-affected horses.
      Histologic examination of the laminar dermis disclosed microthrombi in venules of
      the laminar dermis in 2 of 4 affected horses. Statistically significant changes
      in prothrombin time were not observed, and changes in activated partial
      thromboplastin time were slight and occurred only at the onset of lameness.
      Statistically significant changes in monocyte procoagulant activity were not
      observed. Plasma endotoxin-like activity was not detected in laminitis-affected
      horses. These data indicate that platelet survival was decreased within the first
      6 hours after induction of carbohydrate-induced laminitis, but systemic
      activation of the coagulation system was not detected.

PMID- 8533990
TI  - Effect of long-term administration of a prolonged release formulation of bovine
      somatotropin (sometribove) on clinical lameness in dairy cows.
AB  - A matched case-control study design was used to assess the effects of long-term
      administration of a prolonged release formulation of bovine somatotropin
      (sometribove) on clinical lameness and limb lesions in dairy cows. Cows treated
      with sometribove for at least 2 lactations (cases) and nontreated dairy cows
      matched by herd, parity, age, and stage of lactation (controls) in 8 herds were
      evaluated for clinical lameness (as assessed by gait abnormality) and limb
      lesions by 2 observers, using a standardized scoring procedure at a single herd
      visit. Although a high proportion of the study cows were clinically lame (43%),
      an association was not detected between chronic administration of sometribove and
      prevalent lameness. Of 21 types of limb lesions identified, 2 were positively
      associated and 2 were negatively associated with long-term sometribove use.
      Superficial laceration of the tarsus (odds ratio [OR] = 2.1) and superficial
      swelling of the metatarsophalangeal joint (OR = 4.5) were positively associated
      with sometribove treatment, whereas femoral lesions (OR = 0.2) and superficial
      lacerations of the femur (OR = 0.14) were negatively associated with sometribove
      treatment.

PMID- 8533991
TI  - Regulation of neutrophil adhesion molecules and shedding of Staphylococcus aureus
      in milk of cortisol- and dexamethasone-treated cows.
AB  - The effects of 3 days of glucocorticoid administration on bovine blood neutrophil
      expression of L-selectin and CD18, and on the health status of mammary glands
      subclinically infected with Staphylococcus aureus were measured in 9 lactating
      Holsteins. The experiment was a 3 x 3 Latin square cross-over design, with 3
      glucocorticoid treatments switched among groups of 3 cows/treatment during 3
      periods. Treatments consisted of a vehicle (control, 10 ml of excipient/cow/d),
      cortisol (7.5, 15, and 7.5 mg/cow on days 1, 2, and 3, respectively), and
      dexamethasone (0.04 mg/kg of body weight/cow/d for total daily dosages that
      ranged from 21.6 to 33.2 mg). Blood samples for immunostaining and flow
      cytometric analysis of L-selectin and CD18 and leukograms, as well as foremilk
      samples for determination of S aureus shedding, somatic cell counts, protein and
      fat percentages, and daily milk yields were collected repeatedly before, during,
      and after treatment days. Dexamethasone caused a profound, acute, short-lived
      down-regulation of L-selectin on neutrophils, which correlated in time to
      leukocytosis, mature and immature neutrophilias, increased shedding of S aureus
      in infected glands, and onset of high percentages of fat and protein and
      decreased milk yields. Dexamethasone also caused profound but delayed down
      regulation of neutrophil CD18, which reached nadir simultaneously with
      reappearance of L-selectin-bearing neutrophils, normalized blood neutrophil
      counts, markedly high foremilk somatic cell counts and protein percentage,
      decreased S aureus shedding in milk, and finally, expression of clinical mastitis
      in some infected quarters. Each of these variables had returned to control
      (vehicle) values by the ninth (and last) sample collection day. Although cortisol
      treatment also decreased expression of L-selectin and CD18 on neutrophils,
      dosages used in this study were not sufficient to alter the number of circulating
      cells or to convert subclinical mammary gland infections to clinical mastitis.
      These results suggest that mammary gland health status can be altered by sudden
      exposure of blood neutrophils to glucocorticoids, because these steroid hormones
      caused profound down-regulation of the adhesion molecules that direct neutrophil
      margination and migration through the vascular endothelium. The results also
      reinforce the potential disease risk of treating infected animals with potent
      synthetic glucocorticoids, such as dexamethasone.

PMID- 8533992
TI  - Clinical-experimental interactions in the development of neuroscience. A primer
      for nonspecialists and lessons for young scientists.
AB  - In the article, the author gives examples of some aspects of the development of
      neuroscience that may be of particular interest to the nonspecialist. In addition
      to the scientific discoveries involved, the examples illustrate how astute
      observations in the clinic can draw the attention of workers in the laboratory to
      significant new problems and how experiments in the laboratory can provide
      foundations for new clinical applications. These examples also illustrate general
      lessons that young investigators may find useful and point to the importance of
      facilitating communications among psychology's fragmenting specialties.

PMID- 8533993
TI  - Axial bone mass in older women. Study of Osteoporotic Fractures Research Group.
AB  - OBJECTIVE: To determine the anthropometric, historical, and lifestyle factors
      associated with bone mineral density (BMD) of the spine and proximal femur in
      older women. DESIGN: Cross-sectional analyses. SETTING: Four clinical centers in
      Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the
      Monongahela Valley, Pennsylvania. PARTICIPANTS: 7963 ambulatory, nonblack women
      65 year of age or older. MEASUREMENTS: Medical history was obtained by
      questionnaire and interview, and physical and anthropometric data were obtained
      by examination. Lumbar spine and proximal femoral BMDs were measured using dual
      energy x-ray absorptiometry. RESULTS: The multivariable models could predict 21%
      and 25% of the difference between participants in BMD at the femoral neck and
      lumbar spine, respectively. Weight was most highly associated with BMD.
      Postmenopausal estrogen use and other indicators of total estrogen exposure were
      strongly associated with increased BMD. Use of diuretics (both thiazide and
      nonthiazide), activity levels and muscle strength, alcohol intake, and dietary
      calcium intake were associated with higher BMD. A family history of osteoporotic
      fracture was strongly associated with low BMD. European ancestry and blond hair,
      childbirth or breast feeding, a history of hyperthyroidism, and progestin use
      were not associated with axial BMD. CONCLUSIONS: Weight is strongly associated
      with BMD. Estrogen exposure, physical activity, and calcium intake are also
      positively associated with BMD, whereas a family history of osteoporosis is
      associated with reduced BMD. These associations suggest ways to better identify
      risk for fracture.

PMID- 8533994
TI  - Hypernatremia in hospitalized patients.
AB  - OBJECTIVE: To determine the incidence, clinical characteristics, and outcome for
      general medical-surgical hospital patients with hypernatremia. DESIGN: A
      prospective cohort study. SETTING: A 942-bed urban university hospital. PATIENTS:
      All patients who developed a serum sodium concentration of 150 mmol/L or greater
      during a 3-month observation period. MEASUREMENTS: Daily fluid balance, mental
      status, and serum and urine electrolytes and osmolality. RESULTS: 103 patients
      were identified. Eighteen patients were hypernatremic on hospital admission, and
      85 developed hypernatremia during hospitalization. Patients who developed
      hypernatremia during hospitalization were younger than patients who developed
      hypernatremia before hospital admission (mean age +/- SD, 58.9 +/- 19.2 years
      compared with 76.6 +/- 16.6 years; P < 0.01) but did not differ in age from the
      patients of the general hospitalized population. Eighty-nine percent of patients
      who developed hypernatremia during hospitalization had urine concentrating
      defects, primarily as the result of the use of diuretics or of solute diuresis,
      whereas only 50% of patients who were hypernatremic on admission could be shown
      to have concentrating defects (P < 0.01). Fifty-five percent of all hypernatremic
      patients had increased insensible water losses, and 35% had increased enteral
      water losses. Eighty-six percent of patients with hospital-acquired hypernatremia
      lacked free access to water, 74% had enteral water intake of less than 1 L/d, and
      94% received less than 1 L of intravenous electrolyte-free water per day during
      the development of hypernatremia. No supplemental electrolyte-free water was
      prescribed during the first 24 hours of hypernatremia in 49% of patients. The
      duration of hypernatremia was shorter in patients who were hypernatremic on
      admission (median duration, 3 days) than in patients with hospital-acquired
      hypernatremia (median duration, 5 days; P < 0.05). Mortality was 41% for all
      patients, but hypernatremia was judged to have contributed to mortality in only
      16% of patients. CONCLUSIONS: Although the development of hypernatremia before
      hospital admission occurs primarily in geriatric patients, hospital-acquired
      hypernatremia was more common in our cohort and had an age distribution similar
      to that of the general hospitalized population. Hospital-acquired hypernatremia
      was primarily iatrogenic, resulting from inadequate and inappropriate
      prescription of fluids to patients with predictably increased water losses and
      impaired thirst or restricted free water intake or both. Treatment of
      hypernatremia is often inadequate or delayed. Efforts to manage hypernatremia
      better and altogether avoid hospital-acquired hypernatremia should focus on both
      physician education and the development of hospital systems to prevent errors in
      fluid prescription.

PMID- 8533995
TI  - An oral preparation of mesalamine as long-term maintenance therapy for ulcerative
      colitis. A randomized, placebo-controlled trial. The Mesalamine Study Group.
AB  - OBJECTIVE: To compare the safety and efficacy of a pH-sensitive, polymer-coated
      oral formulation of mesalamine (Asacol, Procter & Gamble Pharmaceuticals,
      Cincinnati, Ohio) with those of placebo in maintaining remission in patients with
      ulcerative colitis. DESIGN: Multicenter, double-blind, placebo-controlled,
      randomized clinical trial. SETTING: Eight private practices, five university
      based medical centers, and four hospitals or clinics. PATIENTS: 264 patients with
      ulcerative colitis that had been maintained in remission for at least 1 month
      while the patients were receiving stable doses of sulfasalazine or any oral
      mesalamine product. INTERVENTION: Coated mesalamine at oral dosages of 0.8 g/d or
      1.6 g/d or matching placebo for 6 months. MEASUREMENTS: Treatment success,
      defined as maintenance of remission after 6 months, and treatment failure,
      defined as relapse during the study (as indicated by proctosigmoidoscopy at 1, 3,
      or 6 months of treatment) or withdrawal due to adverse events. Safety was
      assessed on the basis of laboratory analyses and patient- and investigator-noted
      adverse events. RESULTS: 189 patients were compliant with the protocol for 6
      months or stopped receiving therapy because of relapse or adverse events. Of
      these 189 patients, 25 of the 63 patients (39.7%) in the placebo group had
      treatment success compared with 40 of the 68 patients (58.8% [95% CI, 46.4% to
      71.3%]) in the group receiving mesalamine, 0.8 g/d (P = 0.036) and 38 of the 58
      patients (65.5% [CI, 52.4% to 78.6%]) in the group receiving mesalamine, 1.6 g/d
      (P = 0.006). In the intention-to-treat analysis of all patients, 42 of the 87
      patients (48.3%) in the placebo group had treatment success compared with 57 of
      the 90 patients (63.3% [CI, 52.8% to 73.8%]) in the group receiving mesalamine,
      0.8 g/d (P = 0.050) and 61 of the 87 patients (70.1% [CI, 59.9% to 80.3%]) in the
      group receiving mesalamine, 1.6 g/d (P = 0.005). Age, sex, and race were not
      found to predict treatment success or failure. The mesalamine tablet was well
      tolerated, and no clinically significant changes were seen in hematologic,
      hepatic, or renal laboratory profiles. CONCLUSION: Coated mesalamine at oral
      dosages of 0.8 g/d and 1.6 g/d is safe and effective in maintaining remission in
      patients with quiescent ulcerative colitis.

PMID- 8533996
TI  - Interferon-alpha 2b added to melphalan-prednisone for initial and maintenance
      therapy in multiple myeloma. A randomized, controlled trial. The Nordic Myeloma
      Study Group.
AB  - OBJECTIVE: To evaluate the addition of low-dose interferon-alpha 2b to standard
      melphalan-prednisone therapy in patients with multiple myeloma. DESIGN:
      Randomized, multicenter, phase III study. SETTING: 15 university hospitals and 92
      county hospitals in Sweden, Norway, Denmark, Finland, and Iceland. PATIENTS: 583
      patients with symptomatic multiple myeloma. INTERVENTION: All patients received
      melphalan-prednisone every 6 weeks. Melphalan-prednisone therapy was interrupted
      after at least 8 courses in responding patients who achieved a plateau phase, and
      it was reinstituted at time of relapse. Patients randomly assigned to receive
      melphalan-prednisone and interferon also received interferon, 5 MU three times
      weekly, from the start of treatment through response, plateau phase, and relapse,
      until definitive failure of melphalan-prednisone occurred. MEASUREMENTS: Survival
      was the main outcome measure. Secondary measures were response rate, response and
      plateau phase duration, and toxicity. All analyses were done according to the
      principle of intention-to-treat. RESULTS: 45% of patients receiving melphalan
      prednisone and 44% of patients receiving melphalan-prednisone and interferon
      achieved at least a partial response. Response duration and plateau phase
      duration were longer for patients receiving melphalan-prednisone and interferon
      than for patients receiving melphalan-prednisone alone (P < 0.05); the difference
      in median duration was 5 to 6 months. Toxicity was higher with melphalan
      prednisone and interferon, and this led to premature discontinuation of
      interferon therapy in one third of patients and to a reduced overall dose
      intensity for melphalan. The median survival time was 29 months for patients
      receiving melphalan-prednisone and 32 months for patients receiving melphalan
      prednisone and interferon. The risk ratio for death for patients receiving
      melphalan-prednisone compared with patients receiving melphalan-prednisone and
      interferon was 1.02 (95% CI, 0.89 to 1.40). CONCLUSIONS: Adding continuous low
      dose interferon to standard melphalan-prednisone therapy does not improve
      response rate or survival. However, response duration and plateau phase duration
      are prolonged by maintenance therapy with interferon.

PMID- 8533997
TI  - Increased allergen-specific, steroid-sensitive gamma delta T cells in
      bronchoalveolar lavage fluid from patients with asthma.
AB  - OBJECTIVE: To test the hypothesis that allergen-specific, steroid-sensitive gamma
      delta T lymphocytes are increased in bronchoalveolar lavage fluid of patients
      with asthma. DESIGN: Case series. SETTING: The outpatient allergy services at the
      University of Perugia, Perugia, Italy. PATIENTS: 12 untreated atopic patients (6
      children and 6 adults) with mildly symptomatic chronic asthma were studied.
      Bronchoalveolar lavage fluid from 10 healthy non-smoking volunteers and age
      matched children with cystic fibrosis (n = 5) or anatomic malformation of the
      airways (n = 4) served as control samples. INTERVENTION: Three patients received
      treatment with deflazacort, 60 mg twice daily, for 1 week. MEASUREMENTS: CD3+,
      CD4+, and CD8+ T cells from patients and controls were examined by two-color flow
      cytometry for coexpression of V delta 1 and V delta 2 isoforms of the gamma delta
      T-cell receptor. In vitro pulmonary gamma delta T-cell proliferation in response
      to a specific allergen, the apoptotic death of these cells after incubation with
      10(-7) M dexamethasone, and bronchoalveolar lavage fluid T-lymphocyte composition
      before and after 1 week of deflazacort therapy were evaluated in 3
      Dermatophagoides pteronyssinus-sensitive patients. RESULTS: The proportion of
      gamma delta T lymphocytes, primarily CD4+ or CD4- CD8- cells, was higher in
      asthmatic patients than in controls (P < 0.05 by one-way analysis of variance).
      Most lung gamma delta CD4+ lymphocytes expressed the gamma delta T-cell receptor
      V delta 1 chain. These cells proliferated in response to allergen stimulation,
      underwent steroid-induced apoptosis in vitro, and disappeared after systemic
      steroid treatment. CONCLUSIONS: Allergen-specific, steroid-sensitive gamma delta
      T cells may be one of the cellular components involved in the airway inflammation
      that characterizes allergic bronchial asthma.

PMID- 8533998
TI  - Neurotoxicity related to the use of topical tretinoin (Retin-A)

PMID- 8533999
TI  - What is accountability in health care?
AB  - Accountability has become a major issue in health care. Accountability entails
      the procedures and processes by which one party justifies and takes
      responsibility for its activities. The concept of accountability contains three
      essential components: 1) the loci of accountability--health care consists of at
      least 11 different parties that can be held accountable or hold others
      accountable; 2) the domains of accountability--in health care, parties can be
      held accountable for as many as six activities: professional competence, legal
      and ethical conduct, financial performance, adequacy of access, public health
      promotion, and community benefit; and 3) the procedures of accountability,
      including formal and informal procedures for evaluating compliance with domains
      and for disseminating the evaluation and responses by the accountable parties.
      Different models of accountability stress different domains, evaluative criteria,
      loci, and procedures. We characterize and compare three dominant models of
      accountability: 1) the professional model, in which the individual physician and
      patient participate in shared decision making and physicians are held accountable
      to professional colleagues and to patients; 2) the economic model, in which the
      market is brought to bear in health care and accountability is mediated through
      consumer choice of providers; and 3) the political model, in which physicians and
      patients interact as citizen-members within a community and in which physicians
      are accountable to a governing board elected from the members of the community,
      such as the board of a managed care plan. We argue that no single model of
      accountability is appropriate to health care. Instead, we advocate a stratified
      model of accountability in which the professional model guides the physician
      patient relationship, the political model operates within managed care plans and
      other integrated health delivery networks, and the economic and political models
      operate in the relations between managed care plans and other groups such as
      employers, government, and professional associations.

PMID- 8534000
TI  - A professional response to demands for accountability: practical recommendations
      regarding ethical aspects of patient care. Working Group on Accountability.
AB  - Forceful new demands for accountability in medicine are arising from many
      interested parties. To maintain professional standards, physicians need to
      establish which demands are desirable and which are not. We adopt a model of
      stratified accountability that includes three major components: the accountable
      parties, the subject matter, and the processes for accountability. To begin
      describing the model, we focus on physicians and health care institutions. We
      focus on the ethical dimensions of medical practice, both because the difficulty
      of measuring such behaviors makes this a test case for accountability and because
      of the importance of ethical standards in maintaining patient trust. We first
      identify eight widely endorsed content areas for accountability in ethical
      conduct: medical decision making, confidentiality, fiduciary obligations
      (including conflicts of interest), responsibilities arising from patient
      vulnerability, personal standards, equity among patients, cultural
      representation, and procedures for resolving dilemmas. We then identify the
      currently most valid and reliable methods for assessing conduct: surveys among
      all involved parties, testing methods used for accreditation, limited audits,
      publication of policy, and careful use of report cards. A prototypical survey and
      report card are illustrated. However, we also note the need for improved
      accountability assessment methods. We next identify mechanisms for taking
      responsibility: sharing information, exchanging perspectives, making adjustments,
      and enforcing standards when necessary. Finally, because this report only begins
      to describe a small part of the accountability model, we urge explicit
      identification and development of professional standards for accountability in
      the many other areas of medicine.

PMID- 8534001
TI  - The 1990 Florida Dental Investigation: is the case really closed?
AB  - In 1994, a magazine article, a newspaper article, and a segment of the television
      newsmagazine 60 Minutes presented information that cast doubt on the Centers for
      Disease Control and Prevention's conclusion that a dentist in Florida had
      infected six of his patients with the human immunodeficiency virus (HIV). These
      reports were based on previously unavailable documentary evidence, which
      suggested that the infected patients had unreported or undetected risk factors
      for HIV infection and that the molecular analyses used to determine that the
      dentist and his patients had the same strains of HIV had potentially serious
      flaws. A recent article in this journal sought to dismiss the relevance of this
      information in the eyes of the scientific community. That report, however, failed
      to respond directly to many key pieces of evidence, and it offered no rebuttal
      beyond personal invective and a reassertion of previously published material.
      Although scientists and clinicians should not rely solely on media reports when
      drawing conclusions about this complex and controversial case, they deserve a
      chance to consider and reflect on this material in a meaningful way.

PMID- 8534002
TI  - The 1990 Florida Dental Investigation: theory and fact.
AB  - Controversy remains about the Centers for Disease Control and Prevention's (CDC)
      conclusion that a dentist in Florida transmitted human immunodeficiency virus to
      six of his patients in the late 1980s. The most vocal doubt has come from
      journalists affiliated with the television program 60 Minutes. Although
      unanswered questions about the case remain, the evidence continues to
      overwhelmingly support the CDC's theory. The criticism of the CDC investigation
      consists largely of assertions that contrary evidence theoretically might exist.

PMID- 8534003
TI  - Asklepios: ancient hero of medical caring.
AB  - Western culture's demands of integrity, sacrifice, and compassion from its
      physician healers have roots in the mythic traditions of ancient Greece. By
      understanding these traditions, modern physicians can better understand their
      patients' expectations and the high expectations physicians often have for
      themselves. The mythic figure Asklepios was the focus of Greek and Roman medical
      tradition from approximately 1500 BC to 500 AD. As a physician-hero, Asklepios
      exemplified the ideal physician and the pitfalls he or she may face. With the
      progressive deification of Asklepios and the spread of his worship first in
      Greece and then in the Roman empire, Asklepios became generally recognized as the
      god of healing and served as an object of supplication, particularly for the poor
      and disregarded. Asklepian traditions for medical service provide historical
      insight into the role of modern physicians and their obligations to care for the
      underserved.

PMID- 8534004
TI  - Whither interferon for myeloma and other hematologic malignancies?

PMID- 8534005
TI  - Gamma delta T cells in asthma.

PMID- 8534006
TI  - Oregon's assisted suicide vote: the silver lining.

PMID- 8534007
TI  - On being a patient.

PMID- 8534008
TI  - For Corrie.

PMID- 8534009
TI  - Cognitive impairment in primary care.

PMID- 8534010
TI  - Burkholderia cepacia and nebulized albuterol.

PMID- 8534011
TI  - Minibronchoalveolar lavage by respiratory therapists.

PMID- 8534012
TI  - Helicobacter pylori eradication in gastric mucosa-associated lymphoid tissue
      lymphomas.

PMID- 8534013
TI  - Interferon for chronic hepatitis B.

PMID- 8534014
TI  - Interferon for chronic hepatitis B.

PMID- 8534015
TI  - Infection risks to patients from HIV-infected health care workers.

PMID- 8534016
TI  - Transient pulmonary infiltrates: a hypersensitivity reaction to paclitaxel.

PMID- 8534017
TI  - Hemorrhagic proctosigmoiditis and Blastocystis hominis infection.

PMID- 8534018
TI  - Health values of the seriously ill.

PMID- 8534019
TI  - Airway measurement using morphometric analysis.
AB  - Measurement of airway size using endoscopic morphometry was investigated.
      Endoscopic images of the porcine tracheobronchial tree were obtained via a Storz
      system at a known distance from the telescope. The bronchi were marked with
      transluminal wires, transected, and imaged. All images were analyzed
      morphometrically with a computer image at multiple sites (N = 20). The endoscopic
      measurements were plotted against the macro lens images so that a straight line
      with a slope of 1 would indicate a consistent correlation. Area measurements for
      all images had a slope of 0.67 (r = .885); however, for images with area < 80 mm2
      the slope was 1 (r = .879), for images with area < 80 mm2 of 0.93 (r = .875), and
      for images with area > 80 mm2 of -0.34 (r = .482), and major axis had a slope for
      all images of 0.73 (r = .904), for images with area < 80 mm2 of 0.88 (r = .923),
      and for images with area > 80 mm2 of -0.59 (r = .771). Accurate area measurements
      as well as major and minor axis measurements can be obtained for airways with
      area < 80 mm2 by means of this system. Each bronchoscope-telescope unit has an
      optimal target size for which measurements are accurate.

PMID- 8534020
TI  - Age-related changes of the macula flava of the human vocal fold.
AB  - This investigation was carried out to determine the histologic structure and age
      related changes of the macula flava of human aged vocal folds. Excised human
      adult senescent larynges served as the material for this study. Light microscopic
      and transmission electron microscopic observations were made. The results are
      summarized as follows. 1) The anterior and posterior maculae flavae were
      elliptical in shape and about 1.5 x 1.5 x 1 mm in size. 2) The macula flava was
      composed of fibroblasts, elastic fibers, collagenous fibers, and ground
      substance. 3) The number of fibroblasts decreased. 4) Components in the
      cytoplasm, such as Golgi apparatus and rough endoplasmic reticulum, were fewer
      than in younger adults. 5) Some fibroblasts and some components in the cytoplasm
      degenerated. 6) The accumulation of glycogen granules and lipid droplets were
      seen in the cytoplasm. 7) The number of collagenous and elastic fibers
      synthesized by the fibroblasts decreased. 8) These findings were evident to
      various degrees and suggested the reduction of fibroblast activation, abnormal
      metabolism, and degeneration. A decrease in the number and activation of
      fibroblasts in maculae flavae indicates decreased synthesis of fibrous components
      in the vocal fold mucosa. This in turn influences the viscoelasticity and
      stiffness of vibrating tissue and contributes partially to aging of the voice.

PMID- 8534021
TI  - Bilateral maxillectomy and midfacial reconstruction.
AB  - Extensive bilateral midfacial defects including the upper jaw, palate, and
      sinuses present a formidable reconstructive challenge. Prosthetic restorations
      require a solid anchor point to be successful, since orofacial motion would
      otherwise cause instability of the prosthesis. We report on a series of eight
      patients who underwent transmalar placement of a Steinmann pin at the time of
      definitive tumor resection. The Steinmann pin was used immediately to securely
      anchor a prosthesis to the skull base. The maximum follow-up time is 9 years. The
      Steinmann pin has remained firmly anchored without significant loosening in six
      of these eight patients, and no major complications have resulted from its use.
      In conclusion, the transmalar Steinmann pin is an effective and immediate single
      stage method of permanently retaining a midface prosthesis.

PMID- 8534022
TI  - Gore-Tex for nasal augmentation: a recent series and a review of the literature.
AB  - Gore-Tex soft tissue patches were used in 12 cases for augmentation during
      rhinoplasty. This synthetic material proved to be completely inert and tissue
      compatible. There were no cases of untoward effects such as overlying skin
      changes, infection, or implant extrusion. A literature review reveals a total of
      52 reported cases of nasal augmentation with Gore-Tex. Similar results were
      reported in these studies. By all reports, Gore-Tex is an acceptable synthetic
      implant for nasal dorsal augmentation, when autogenous cartilage is not available
      or would require a second procedure for harvesting.

PMID- 8534023
TI  - Otorhinolaryngological complications of progressive facial hemiatrophy (Romberg's
      disease).
AB  - Progressive facial hemiatrophy (PFH) is characterized by slowly progressive
      atrophy of subcutaneous tissue. Bone, muscles, nerves, the eye, and the brain may
      be affected by atrophy. Four patients suffering from various
      otorhinolaryngological complications of PFH or Romberg's disease are reported.
      Unilateral hearing loss could be located in the inner ear of one patient by
      audiologic examination. Localized bone destruction and disintegration of a
      portion of the anterior wall of the frontal sinus were observed in a patient
      after more than three decades. Marked shrinking of the homolateral parotid gland
      and homolateral masticatory spasm are reported as further otorhinolaryngological
      manifestations. The various complications of PFH call for close interdisciplinary
      cooperation.

PMID- 8534024
TI  - Na,K-ATPase in the cochlear lateral wall of human temporal bones with
      endolymphatic hydrops.
AB  - Meniere's disease has traditionally been thought to arise from a disruption in
      longitudinal endolymphatic flow. This view has been brought into question by
      recent experimental studies that have focused attention on derangements of
      cochlear fluid and electrolyte homeostatic mechanisms in Meniere's disease,
      including abnormalities in Na,K-ATPase enzymes found in the cochlear lateral
      wall. The current study examined the immunohistochemical labeling pattern of the
      major ion-transporting enzyme of the stria vascularis, Na,K-ATPase, in archival
      sections of hydropic and nonhydropic human temporal bones for increased density
      of label that could indicate overproduction of fluid. The results showed good
      labeling of the stria vascularis in the celloidin sections. The hydropic ears
      tended to have darker label, but the difference was not statistically
      significant. The findings are consistent with normal functioning of the stria
      vascularis in cases of Meniere's disease.

PMID- 8534025
TI  - Hearing loss in Behcet's disease.
AB  - In order to determine the characteristics and incidence of hearing loss in
      Behcet's disease, 72 consecutive cases and 72 sex- and age-matched normal
      subjects were submitted to this study. Detailed audiologic tests were performed
      in all cases. Twenty patients (27%) showed some degree of hearing loss; but in
      only 7 patients (9%) was the average of the frequencies between 500 to 4,000 Hz
      more than 25 dB hearing level, and the cochlear function of 43 patients (59%) was
      within the 25-dB range in all frequencies. The averaged pure tone audiograms of
      the two groups showed a statistically significant hearing loss in the Behcet's
      group. No relationship could be found between hearing loss and other system
      involvements. There was no correlation between hearing loss and duration of the
      disease, but the mean age of the Behcet's patients with hearing loss was found to
      be significantly higher than the mean age of the patients without hearing loss.

PMID- 8534026
TI  - External ear canal cholesteatoma. Case report.
AB  - External ear canal cholesteatoma is a rare condition in otologic practice. A case
      in a 43-year-old woman is presented in which despite the extensive nature of the
      lesion, minimal symptoms and absence of signs delayed diagnosis. The cause of the
      lesion and its treatment are discussed.

PMID- 8534027
TI  - Long-term result of vocal cord augmentation with autogenous fat.
AB  - The use of autogenous fat for augmentation of the paralyzed vocal fold is a
      promising substitute for alternate injectable material such as Teflon (polytef
      paste, polytetrafluoroethylene; Ethicon) and Gelfoam (absorbable gelatin sponge;
      Upjohn). Long-term histologic evaluation of fat grafts to the larynx has not
      previously been reported in the literature. We present a case report of
      autogenous fat augmentation of a paralyzed vocal fold with documentation of
      persistent fat graft present 5 months after transplant.

PMID- 8534028
TI  - Comparison of rabbit facial nerve regeneration in nerve growth factor-containing
      silicone tubes to that in autologous neural grafts.
AB  - Previous reports suggest that nerve growth factor (NGF) enhanced nerve
      regeneration in rabbit facial nerves. We compared rabbit facial nerve
      regeneration in 10-mm silicone tubes prefilled with NGF or cytochrome C (Cyt C),
      bridging an 8-mm nerve gap, to regeneration of 8-mm autologous nerve grafts.
      Three weeks following implantation, NGF-treated regenerates exhibited a more
      mature fascicular organization and more extensive neovascularization than Cyt C
      treated controls. Morphometric analysis at the middle of the tube of 3- and 5
      week regenerates revealed no significant difference in the mean number of
      myelinated or unmyelinated axons between NGF- and Cyt C-treated implants.
      However, when the numbers of myelinated fibers in 5-week regenerates were
      compared to those in their respective preoperative controls, NGF-treated
      regenerates had recovered a significantly greater percentage of myelinated axons
      than Cyt C-treated implants (46% versus 18%, respectively). The number of
      regenerating myelinated axons in the autologous nerve grafts at 5 weeks was
      significantly greater than the number of myelinated axons in the silicone tubes.
      However, in the nerve grafts the majority of the axons were found in the
      extrafascicular connective tissue (66%). The majority of these myelinated fibers
      did not find their way into the distal nerve stump. Thus, although the number of
      regenerating myelinated axons within the nerve grafts is greater than that of
      axons within silicone tube implants, functional recovery of autologous nerve
      graft repairs may not be superior to that of intubational repairs.

PMID- 8534029
TI  - Comparison of endolymph cross-sectional area measured histologically with that
      measured in vivo with an ionic volume marker.
AB  - In order to establish how endolymph volume is regulated, it is essential to be
      able to measure endolymph volume or cross-sectional area in vivo. We have
      developed methods to accomplish this by injecting the volume marker ion
      hexafluoroarsenate (AsF6) into endolymph by iontophoresis. For an injection at a
      constant rate, the endolymph concentration is inversely dependent on the cross
      sectional area of the scala into which injection occurred. Marker concentrations
      were monitored by inserting ion-selective microelectrodes into endolymph near the
      injection site. In a previous study we quantified the degree of hydrops in
      animals following ablation of the endolymphatic sac. In the present study we
      validated the technique by comparing the endolymphatic cross-sectional area
      measured in vivo with AsF6 with that measured by established histologic
      procedures. The correlation between the two measures was good, with a coefficient
      of .903, although the area measured histologically was a little lower than that
      measured in vivo.

PMID- 8534030
TI  - Horseradish peroxidase permeability across rat nasal mucosa in selective
      stimulation of substance P innervation with capsaicin.
AB  - To investigate the physiological role of substance P innervation (SPI) in the
      nasal mucosa from inhaled irritant macromolecules, SPI in the rat nasal mucosa
      was selectively stimulated with capsaicin and the degree of horseradish
      peroxidase (HRP) permeability across the nasal epithelium was evaluated by enzyme
      immunoassay or by histochemical electron microscopy. The serum level of HRP was
      reduced significantly in capsaicin-administered rats compared to control rats
      along the time course with quantitative analysis of the enzyme immunoassay.
      Control rats showed heavy permeation of HRP across the epithelium, but capsaicin
      administered rats showed weak permeation of HRP across the epithelium with
      histochemical electron microscopy. The epithelial lining and its tight junctions
      were left intact as judged by electron microscopy. In conclusion, selective
      stimulation of SPI of the rat nasal mucosa with capsaicin decreased the
      epithelial absorption permeability to HRP without compromising the epithelial
      integrity. These findings imply that the physiological role of capsaicin
      sensitive SPI in the rat mucosa is to protect the airway from inhaled irritant
      macromolecules.

PMID- 8534031
TI  - Internal jugular vein thrombosis.

PMID- 8534032
TI  - Bilateral extra-articular condylar neck fracture.

PMID- 8534033
TI  - Mucocele of the inferior turbinate.

PMID- 8534034
TI  - Developmental lesions of the head and neck: terminology and biologic behavior.

PMID- 8534035
TI  - Acute thrombocytopenic purpura in childhood brucellosis.
AB  - Two children who presented with fever, thrombocytopenic purpura and mucosal
      haemorrhages proved to have brucellosis. Large platelets in the peripheral smear
      and megakaryocytic hyperplasia in the bone marrow suggested increased peripheral
      destruction as the primary mechanism of the thrombocytopenia. There was a prompt
      clinical and haematological response to specific anti-brucella chemotherapy. The
      nature of this association and its implications for brucella-endemic areas are
      discussed.

PMID- 8534036
TI  - Type b Haemophilus influenzae endocarditis in children: case report and review of
      the literature.
AB  - Haemophilus influenzae type b (Hib) endocarditis is a rare but potentially lethal
      condition. Only ten cases have been reported in the English literature. This
      report describes an 8-month-old Malay child with a ventricular septal defect who
      developed Hib endocarditis and died after 4 weeks of hospitalization. The
      literature is reviewed and previously reported cases summarized.

PMID- 8534037
TI  - Delayed sexual maturation in sickle cell anaemia patients--observations in one
      practice.
AB  - Pubic hair and breast appearance ratings, testicular volumes and age at menarche
      were determined in 24 sickle cell anaemia patients aged from 8.5 to 27 years
      between February and September 1994 in the Wesley Guild Hospital, Ilesa, Nigeria.
      Only three of the six females aged 15 or more years had experienced menarche and
      this was at the mean (SD) age of 18.8 (4.5) years. Public hair appearance and
      breast development had commenced in only six and seven, respectively, of the 12
      females, and in every case the ratings were significantly low for their ages.
      Male testicular volume was also low for their age in the six of 12 males who were
      13 years of age, and above, and pubic hair had appeared in only two of them, aged
      20 and 27 years. The height of all the patients was delayed. It is important to
      recognize that significant delay in sexual development may accompany sickle cell
      anaemia and to take appropriate steps in managing and counselling the patients.

PMID- 8534038
TI  - Ambiguous genitalia: comparative role of pelvic ultrasonography and genitography.
AB  - Ambiguous genitalia represents a true medical and social emergency which needs a
      multi-disciplinary team approach for elucidation. The paediatric radiologist
      plays an important role in defining the genital anatomy which remains one of the
      most important factors in sex determination. Aiming to compare the predictive
      value of pelvic ultrasonography and genitography in sex determination in patients
      with ambiguous genitalia, we retrospectively reviewed the medical records of 69
      patients, 53 females and 16 males, where both procedures were employed. In female
      pseudohermaphroditism, the presence of a uterus with or without vagina was
      predicted in 46 (86.8%) patients by ultrasound compared with 44 (83%) patients in
      whom a genitogram revealed a vagina +/- uterus. In six (11.3%) patients, a
      genitogram revealed a male-type urethra. The combination of ultrasound and
      genitogram, however, was more sensitive and predicted the presence of a uterus
      with or without vagina in 52 (98.1%) patients. In male pseudo-hermaphroditism,
      there was no false positive by ultrasound, and a genitogram revealed a male-type
      urethra in 12 (75%) patients. In conclusion, although real time pelvic
      ultrasonography is less invasive than genitography, its yield in elucidating
      genital anatomy is comparable. The combination of both procedures is more
      informative and has a better yield.

PMID- 8534039
TI  - Aflatoxin and outcome from acute lower respiratory infection in children in The
      Philippines.
AB  - Aflatoxin is immunosuppressive in experimental conditions. This study addressed
      its potentially contributory role in the poor outcome of acute lower respiratory
      infections (ALRI) in children in The Philippines. The catchment area included
      peri-urban slums and middle-class housing. One hundred and fifteen children (mean
      age 2.1, range 0.08-12 years) were enrolled and their serum and urine obtained at
      presentation with ALRI. Aflatoxins in serum and aflatoxin metabolites in urine
      were measured by previously validated ELISA tests. Using the 1986 WHO criteria
      for the severity of ALRI, 31% had mild, 12% moderate, 49% severe and 8% severe
      complicated pneumonia. Eighty of 97 (82%) chest radiographs were abnormal. Ninety
      per cent of the children were below average weight for age, using Filipino
      standards, with a mean of 79% (range 27-157%). Thirteen (11%) children died.
      Aflatoxin in their serum, reflecting recent ingestion, was detected in 33%, with
      a mean positive value of 462 pg/ml. Aflatoxin metabolites (reflecting chronic
      ingestion) were detected in 64 of 65 urines collected, with a mean value of 0.1
      4.77ng/ml. None of the children with detectable serum aflatoxin died. Anorexia
      and impaired consciousness were strongly associated with a poor outcome
      (prolonged fever or death). There was a strong association between undetectable
      serum aflatoxin concentrations and death (p = 0.004), perhaps reflecting
      anorexia. There was no relationship between the concentration of urinary
      aflatoxin metabolites and outcome. Serum was also obtained from 29 mothers on
      admission and none contained detectable aflatoxin. As virtually all the children
      had evidence of exposure to aflatoxin, a potentially immunosuppressive role in
      the context of pneumonia cannot be excluded.

PMID- 8534040
TI  - Two unusual cases of kwashiorkor: can protein deficiency explain the mystery?
AB  - Two children with unusual features of kwashiorkor are reported. One, an
      exclusively breastfed 7-month-old girl, had been admitted earlier, treated for
      pneumonia and discharged 3 weeks before she presented with kwashiorkor. The other
      was an identical twin who was admitted for kwashiorkor and gastro-enteritis. The
      twin sister was underweight but relatively well. Both children died. Potent
      aflatoxins were detected in the organs of these children on post-mortem
      examination. The occurrence of kwashiorkor in a fully breastfed infant and in an
      identical twin does not accord with the extant belief that the aetiology of
      kwashiorkor is wholly nutritional, but suggests a disease probably of
      multifactorial origin.

PMID- 8534041
TI  - The distribution of kwashiorkor in the southern region of Malawi.
AB  - Using existing nutritional survey data collected over an 11-month period during
      the recent drought, we sought to determine the distribution of kwashiorkor in the
      ten districts of the Southern Region of Malawi. Sampling and survey methods were
      identical and considerable efforts were made to ensure comparability. In 23
      surveys, 25,824 children were weighed and measured and oedema was recorded. The
      district-adjusted prevalence of kwashiorkor was 18/1000. The northernmost
      districts of the Southern Region had rates five to ten times higher than the
      southernmost districts. Prevalence peaked at 18-23 months and was similar in boys
      and girls. Dysentery was associated with the presence of kwashiorkor while
      diarrhoea was not. The distinctive pattern of kwashiorkor in the region suggests
      that there are characteristics specific to the northern districts that place
      children in these areas at greater risk of kwashiorkor.

PMID- 8534042
TI  - The prevalence and correlates of anaemia among young children and women of
      childbearing age in Al Ain, United Arab Emirates.
AB  - During 1992 and 1993, 309 children aged 1-22 months (mo) and their mothers
      visiting an immunization facility in Al Ain city, Abu Dhabi Emirate, United Arab
      Emirates, were studied to (1) define blood haemoglobin (Hb) levels; (2) estimate
      the prevalence of anaemia; (3) examine the role of iron deficiency in causing
      anaemia; (4) identify the correlates of anaemia prevalence; and (5) assess the
      acceptability to parents of an anaemia screening test for their young children.
      The levels of Hb in all subjects and the levels of serum ferritin in anaemic (Hb
      < 11 g/dl) children aged > or = 6 mo and in non-pregnant women with Hb < 11 g/dl
      were determined by a HemoCue Photometer and an enzyme immunoassay, respectively.
      Each woman was interviewed to obtain pertinent data. In children, anaemia was
      detected in 3% of those aged 1-2 mo (Hb < 9 g/dl), in 8% of those aged 3-5 mo (Hb
      < 10 g/dl), and in 25-39% of those aged > or = 6 mo (Hb < 11 g/dl). Of 19
      children tested, ten (53%) were iron-depleted (serum ferritin < 12 micrograms/l).
      After multivariate adjustment, the only significant positive correlate of anaemia
      in children was older age (1-5 mo vs 6-22 mo; odds ratio [OR]: 9.51; 95%
      confidence interval [CI]: 3.92-23.08). Anaemia was detected in 14% of pregnant
      women (Hb < 11 g/dl) and 16% of non-pregnant women (Hb < 12 g/dl).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8534043
TI  - Atypical copper cirrhosis in Indian children.
AB  - In addition to ten children with Wilson's disease and one with Indian childhood
      cirrhosis, nine Indian children, aged from 4 to 15 years, with cryptogenic
      cirrhosis had significant deposits of stainable copper in their hepatocytes.
      These nine children had normal or elevated serum caeruloplasmin levels, absence
      of Kayser-Fleischer rings and a history of sibling death owing to liver disease
      in four cases. Histologically, fatty change was absent from all the biopsies but
      Mallory's hyaline, pericellular fibrosis and ballooning of hepatocytes were
      present in some. Since these children did not conform to the accepted clinical or
      histological definitions of either Indian childhood cirrhosis or Wilson's
      disease, they were designated as having atypical copper cirrhosis. The
      relationship of this group of cases to other types of copper cirrhosis is
      unknown.

PMID- 8534044
TI  - Pyogenic meningitis in children in north-western Ethiopia.
AB  - A 5-year retrospective study of all children with acute pyogenic meningitis
      admitted to a district hospital in north-western Ethiopia was carried out from
      1990 to 1994. A total of 132 cases of pyogenic meningitis were identified. The
      causative bacteria were identified in 85 (64%) patients. The most common pathogen
      was Haemophilus influenzae (40%) with a case fatality rate of 29.4%, followed by
      Neisseria meningitidis (36.4%), which had a case fatality rate of 16.1%, and
      Streptococcus pneumoniae (20%) with a case fatality rate of 35.3%. Boys accounted
      for 64% of the patients, giving a male:female ratio of 1.7:1. Median patient age
      was 0.75 years, and median ages of those infected by H. influenzae, N.
      meningitidis, and S. pneumoniae were 0.5, 4.0 and 0.6 years, respectively. The
      overall case fatality rate was 28%. The mortality rate of children below the age
      of 1 year was 38.4% and 13.8% for those above 1 year.

PMID- 8534045
TI  - Isoniazid elimination kinetics in children with protein-energy malnutrition
      treated for tuberculous meningitis with a four-component antimicrobial regimen.
AB  - The impact of changing environmental factors--disease, nutrition and a high-dose
      multi-drug treatment regimen--on isoniazid (INH) elimination kinetics in children
      of both sexes and various ages was investigated. Thirteen children (mean age 2.3
      years), hospitalized for the treatment of tuberculous meningitis, participated in
      the trial. Although all the children had protein-energy malnutrition, none had
      marasmus or kwashiorkor. After an oral dose of 20 mg/kg of INH, the
      concentrations in plasma were determined by the liquid chromatographic method of
      Lacroix et al. The 2-hour post-dose isoniazid concentration, the apparent first
      order elimination rate constant and the corresponding INH half-life were
      determined in each child on two occasions 6 months apart. All comparisons were
      tested for significance using the Wilcoxon matched-pair signed-ranks test. There
      was no significant difference in any of the pharmacokinetic parameters of INH in
      our patients evaluated at the extremes of the 6-month term of treatment. It was
      apparent that changing conditions of disease and nutrition and a high-dosage,
      multi-component antimicrobial agent regimen over a 6-month period of treatment
      did not significantly influence INH elimination parameters. The trend evident in
      the pharmacokinetic profile of isoniazid in our children supports a trimodal
      distribution of acetylator phenotypes.

PMID- 8534046
TI  - Acute viral hepatitis, glucose-6-phosphate dehydrogenase deficiency and prolonged
      acute renal failure: a case report.
AB  - A 10-year-old boy with glucose-6-phosphate dehydrogenase deficiency developed
      acute renal failure during the icteric phase of non-fulminant hepatitis A
      infection. He needed peritoneal dialysis for 54 days. Acute tubular necrosis was
      confirmed by percutaneous renal biopsy. He had complete recovery of his renal
      function when he was discharged.

PMID- 8534047
TI  - Employers and employees share the responsibility for ensuring the safety of
      today's health care workplaces.

PMID- 8534048
TI  - Reduce, reuse, recycle.

PMID- 8534049
TI  - Role redesign.

PMID- 8534050
TI  - Talc poudrage.

PMID- 8534051
TI  - Prostate procedures.

PMID- 8534052
TI  - Residual organic debris.

PMID- 8534053
TI  - Radiolabeled monoclonal antibodies.
AB  - Monoclonal antibodies (MoAbs) are biologically engineered proteins designed to
      bind to antigens emanating from tumor cells. Selected radioactive isotopes are
      fused with MoAbs to allow radioimmunodetection of external imaging of metastatic
      deposits in patients with colon cancer. For the past 10 years, radiolabeled MoAbs
      have improved tumor localization techniques and influenced the clinical
      management of surgical patients. Intraoperatively, surgeons use appropriately
      shielded, handheld, gamma detection probes to locate radiolabeled MoAbs and
      corresponding colon cancers (ie, residual, recurrent tumors). Using gamma
      detection probes intraoperatively, surgeons can localize nonpalpable occult
      tumors and disease not suspected from external antibody scans or other
      traditional diagnostic methods. This success confirms the need for complete tumor
      resections, thorough scanning of entire tumor beds, and ex vivo scanning of
      surgical specimens to assess for potential nodal metastases.

PMID- 8534054
TI  - Experts recommend longer treatment for hepatitis C virus.

PMID- 8534055
TI  - Leech therapy in digital replantation.
AB  - This article presents a protocol for the perioperative care of patients
      undergoing digital replantation, which is the most common microsurgical procedure
      performed today. Venous congestion, a common complication of digital
      replantation, often has been treated through surgical exploration and creation of
      arteriovenous anastomosis. Leech therapy, however, is experiencing a resurgence
      among surgeons as an alternative method for treating venous congestion. This
      article discusses the anatomical, physiological, and clinical indications and
      methods of leech therapy in digital replantation.

PMID- 8534056
TI  - Demographics and patient treatment choice in stage I breast cancer.
AB  - The identification of factors related to patients' treatment selections for
      breast cancer is important to health care providers. This study examined the
      relationship of selected demographics to patient treatment choice for stage I
      breast cancer. The study design was a retrospective chart review from a community
      hospital's tumor registry. The investigators used frequency distributions, chi
      square tests, and factor analyses to analyze a convenience sample of 58 patients
      with stage I breast cancer who registered in 1992 and 1993. The results show that
      education level is a significant influencing factor (p = .02) in patients'
      treatment choices. Perioperative nurses often help patients clarify treatment
      option information and provide support during the decision-making process.
      Demographic factors may affect patients' perceptions of critical information and
      directly influence their treatment choices.

PMID- 8534057
TI  - Surveyed use of fetal and uterine monitoring during maternal surgery.
AB  - The goal of this study was to determine the frequency and methods of
      intraoperative fetal and uterine monitoring during maternal surgery in the United
      States. Maternal surgery was defined as nonobstetric surgery during pregnancy
      that required general or regional anesthesia. We mailed a 21-item questionnaire
      to the perioperative nurse managers of US hospitals at which more than 2,000
      babies are delivered annually (n = 579). Nearly 60% of responding hospitals
      routinely used some form of fetal monitoring during maternal surgery; more than
      40% of responding hospitals did not use intraoperative fetal and uterine
      monitoring routinely during maternal surgery.

PMID- 8534058
TI  - A comparison of two skin preps used in cardiac surgical procedures.
AB  - Postoperative surgical site infections contribute significantly to increased
      patient morbidity and mortality rates and unnecessary hospital costs. Effective
      and efficient preoperative patient skin preparation is an important perioperative
      nursing intervention that decreases the number of wound contaminants and reduces
      the risks for postoperative surgical site infections. This study examined the
      effectiveness and time and material costs of two preoperative patient skin prep
      methods (ie, isopropyl alcohol prep/iodophor-impregnated adhesive drape method,
      iodophor scrub and paint prep/plain adhesive drape method). The isopropyl alcohol
      prep/iodophor-impregnated adhesive drape method clinically was as effective as
      the iodophor scrub and paint prep/plain adhesive drape method, more cost
      effective when time and materials were compared, and less cost-effective when
      materials alone were compared. To make appropriate decisions about the use of
      preoperative patient skin prep methods, perioperative nurse managers and staff
      members need to examine and determine whether costs in time or materials have the
      greater impact on their surgical settings.

PMID- 8534059
TI  - Nurses' educational preparation and attitudes toward cost containment.
AB  - This study examined attitudes toward cost-effectiveness among nurses who were
      stratified according to their highest educational nursing preparation (ie,
      diploma, associate degree, bachelor's degree). A convenience sample of 65 staff
      nurses from OR and intensive care settings participated. Descriptive statistics
      and one-way and two-way analyses of variance were used to analyze the data. Mean
      scores on the Blaney/Hobson Nursing Attitude Scale for the associate degree nurse
      (ADN), diploma, and bachelor of science in nursing (BSN) groups were 69.90,
      76.65, and 81.27, respectively. The diploma- and BSN-prepared staff nurses had
      significantly more favorable attitudes toward cost-containment issues in nursing
      practice than did the ADN group (p = .05).

PMID- 8534060
TI  - A nurse's right to refuse a patient care assignment.
AB  - Ethics is a set of moral principles or values--a guiding philosophy for behavior.
      Ethical dilemmas in the health care setting occur daily. Perioperative nurse
      managers need to consider basic ethical principles when resolving these dilemmas,
      and they must keep in mind that solutions need to serve the best interests of all
      people involved in given situations. This article discusses criteria by which a
      nurse can refuse a patient care assignment and those by which a nurse manager can
      require that a nurse perform a patient care assignment.

PMID- 8534061
TI  - Active and associate AORN membership categories examined.

PMID- 8534062
TI  - Parents beware of accidental overdose of acetaminophen.

PMID- 8534063
TI  - Revascularization versus amputation for elderly patients.

PMID- 8534064
TI  - Emotional distress suits brought after exposure to HIV.

PMID- 8534065
TI  - Knowing what shapes lawmakers' views could help nurses influence policy
      decisions.

PMID- 8534066
TI  - Proposed recommended practices for use and selection of barrier materials for
      surgical gowns and drapes.

PMID- 8534068
TI  - Let us respect and value each other as we celebrate the nature of caring.

PMID- 8534067
TI  - Proposed recommended practices for safe care through identification of potential
      hazards in the surgical environment.

PMID- 8534069
TI  - The way it was--perioperative nursing 50 years ago.

PMID- 8534070
TI  - RN first assistant.

PMID- 8534071
TI  - RN first assistant.

PMID- 8534072
TI  - A salute to the nurses of World War II.
AB  - The nation recently celebrated the 50th anniversary of World War II (WWII) with a
      renewed interest in Pearl Harbor and D-Day (ie, the day the Allies invaded
      Europe.) One group of war heroes--all volunteers--received little attention,
      although they endured bombings, torpedoes, antiaircraft fire, prison, starvation,
      and death. They were the nurses of WWII. They served all over the world and left
      a legacy that today's perioperative nurses are committed to preserving. This
      article was written to honor the nurses of WWII. It relates only a few stories of
      thousands that could be told.

PMID- 8534073
TI  - Laparoscopic Swenson pull-through procedure for congenital megacolon.
AB  - Constipation that is unresponsive to conventional remedies is the primary symptom
      of congenital megacolon (ie, Hirschsprung's disease). The cause of congenital
      megacolon is lack of ganglion cells in the bowel. The laparoscopic Swenson pull
      through procedure involves removing the aganglionic segment of the colon,
      bringing the normally decompressed bowel through the pelvic floor, and
      anastomosing the bowel to the anorectal verge. Advantages of the laparoscopic
      approach include shorter lengths of hospital stay and fewer complications
      resulting from disruption of skin integrity.

PMID- 8534075
TI  - AORN OR Learning Lab hub of educational activity.

PMID- 8534074
TI  - Arthroscopic rotator cuff repairs using suture anchors.
AB  - Arthroscopic rotator cuff repairs using titanium-alloy suture anchors are a new
      treatment option for active patients with shoulder injuries. Shoulder arthroscopy
      and arthroscopic repair procedures are alternative treatments to traditional open
      surgical procedures for Bankart lesions and rotator cuff tears. Distinct
      advantages of arthroscopic repair techniques include decreased patient tissue
      trauma and morbidity rates and shortened recovery and rehabilitation periods.

PMID- 8534076
TI  - A historical decline of educational perioperative clinical experiences.
AB  - This historical study identifies sociocultural and economic influences that have
      contributed to the decline of educational perioperative clinical experiences.
      Three themes were identified: the professional versus the technical role of OR
      nurses debate, the nurse generalist versus the nurse specialist debate, and the
      relative lack of control that nursing has over its own destiny. Recommendations
      to reverse this trend include increasing the visibility of perioperative nurses
      to the public and within the profession of nursing, structuring efforts to
      capitalize on the changes occurring in nursing education, and promoting a
      stronger affiliation between nursing academia and practice settings.

PMID- 8534077
TI  - The effect of humorous and musical distraction on preoperative anxiety.
AB  - This study investigated the effect of humorous and musical distraction on
      preoperative anxiety among 46 patients scheduled for same day, elective,
      nondiagnostic surgery. Preoperative anxiety was measured with a horizontal visual
      analog scale after treatment group subjects listened to either a humorous
      audiotape or a tranquil music audiotape for 20 minutes and control group subjects
      received no intervention. Results show no significant difference between the
      group anxiety means. This study provides no evidence that humor or music
      decreases preoperative anxiety, but it also shows no evidence that perioperative
      nurses should avoid using humor or music as nursing interventions.

PMID- 8534078
TI  - The perioperative nurse's role in anesthesia management.
AB  - The perioperative nurse's role in anesthesia management of the surgical patient
      begins with a preoperative patient assessment and ends when the patient recovers
      from the effects of anesthesia. An understanding of the following concepts
      enhances the perioperative nurse's ability to collaborate with anesthesia care
      providers in providing optimal care: anesthesia risk classifications, choice of
      anesthetic agents, importance of patient positioning, anesthesia induction and
      intubation techniques, levels of general anesthesia, inhalational agents,
      malignant hyperthermia, and patient monitoring parameters during local and
      regional anesthesia.

PMID- 8534079
TI  - A career ladder program designed by perioperative staff nurses.
AB  - Staff members at Baylor University Medical Center, Dallas, were dissatisfied with
      the existing clinical ladder program, so a committee of perioperative staff
      nurses was appointed to create a new program. The new program was based on a
      literature review and RN and management survey data. Under the new program,
      nurses must accumulate points to quality for or maintain clinical nurse levels I,
      II, or III. The point system recognizes many professional contributions that were
      ignored by the previous program.

PMID- 8534080
TI  - Outpatient vaginal hysterectomy as a new trend in gynecology.
AB  - A large number of vaginal hysterectomies are performed on an outpatient basis
      through ambulatory surgery units (ASU). Recognizing this trend, we researched the
      possibility of performing vaginal hysterectomies in our ASU and developed an
      outpatient vaginal hysterectomy protocol. The preoperative and postoperative
      education we provide to patients is the key to our protocol's success. After
      conducting patient satisfaction surveys, we reached the conclusion that
      outpatient vaginal hysterectomies are a successful alternative to inpatient
      vaginal hysterectomies for many of our patients.

PMID- 8534081
TI  - A direct PCR detection method for Clostridium tyrobutyricum spores in up to 100
      milliliters of raw milk.
AB  - A direct detection method for Clostridium tyrobutyricum spores in up to 100 ml of
      raw milk is presented. The bacterial spores are concentrated by centrifugation
      after chemical extraction of the milk components. The vegetative cells are
      selectively lysed, and their DNA is digested and washed away. Afterwards, the DNA
      is liberated from the spores by microwave treatment. For the identification of
      the C. tyrobutyricum DNA, a two-step PCR method with two nested pairs of primers
      is used. The primers were derived from the 16S-23S rRNA spacer region of C.
      tyrobutyricum, and the specificity of each of them for C. tyrobutyricum is
      demonstrated. The detection limit can be estimated to be between 3 and 30 spores
      in 100 ml of raw milk.

PMID- 8534082
TI  - Entry of Escherichia coli into stationary phase is indicated by endogenous and
      exogenous accumulation of nucleobases.
AB  - Endogenous and exogenous accumulation of nucleobases was observed when
      Escherichia coli entered the stationary phase. The onset of the stationary phase
      was accompanied by excretion of uracil and xanthine. Except for uracil and
      xanthine, other nucleobases (except for minor amounts of hypoxanthine),
      nucleosides, and nucleotides (except for cyclic AMP) were not detected in
      significant amounts in the culture medium. In addition to exogenous accumulation
      of nucleobases, stationary-phase cells increased the endogenous concentrations of
      free nucleobases. In contrast to extracellular nucleobases, hypoxanthine was the
      dominating intracellular nucleobase and xanthine was present only in minor
      concentrations inside the cells. Excretion of nucleobases was always connected to
      declining growth rates. It was observed in response to entry into the stationary
      phase independent of the initial cause of the cessation of cell growth (e.g.,
      starvation for essential nutrients). In addition, transient accumulation of
      exogenous nucleobases was observed during perturbations of balanced growth
      conditions such as energy source downshifts. The nucleobases uracil and xanthine
      are the final breakdown products of pyrimidine (uracil and cytosine) and purine
      (adenine and guanine) bases, respectively. Hypoxanthine is the primary
      degradation product of adenine, which is further oxidized to xanthine. The
      endogenous and exogenous accumulation of these nucleobases in response to entry
      into the stationary phase is attributed to degradation of rRNA.

PMID- 8534083
TI  - Polymer production by Klebsiella pneumoniae 4-hydroxyphenylacetic acid
      hydroxylase genes cloned in Escherichia coli.
AB  - The expression of Klebsiella pneumoniae hpaA and hpaH genes, which code for 4
      hydroxyphenylacetic acid hydroxylase in Escherichia coli K-12 derivative strains,
      is associated with the production of a dark brown pigment in the cultures. This
      pigment has been identified as a polymer which shows several of the
      characteristics reported for microbial melanins and results from the oxidative
      activity of 4-hydroxyphenylacetic acid hydroxylase on some dihydroxylated
      compounds to form o-quinones. A dibenzoquinone is formed from the oxidation of
      different mono- or dihydroxylated aromatic compounds by the enzyme prior to
      polymerization. We report a hydroxylase activity, other than tyrosinase, that is
      associated with the synthesis of a bacterial melanin.

PMID- 8534084
TI  - Death of enterohemorrhagic Escherichia coli O157:H7 in real mayonnaise and
      reduced-calorie mayonnaise dressing as influenced by initial population and
      storage temperature.
AB  - This study was undertaken to determine the survivability of low-density
      populations (10(0) and 10(2) CFU/g) of enterohemorrhagic Escherichia coli O157:H7
      inoculated into real mayonnaise and reduced-calorie mayonnaise dressing and
      stored at 20 and 30 degrees C, temperatures within the range used for normal
      commercial mayonnaise distribution and storage. Inactivation patterns at 5
      degrees C and inactivation of high-inoculum populations (10(6) CFU/g) were also
      determined. The pathogen did not grow in either mayonnaise formulation,
      regardless of the inoculum level or storage temperature. Increases in storage
      temperature from 5 to 20 degrees C and from 20 to 30 degrees C resulted in
      dramatic increases in the rate of inactivation. Populations of E. coli O157:H7 in
      the reduced-calorie and real formulations inoculated with a population of 0.23 to
      0.29 log10 CFU/g and held at 30 degrees C were reduced to undetectable levels
      within 1 and 2 days, respectively; viable cells were not detected after 1 day at
      20 degrees C. In mayonnaise containing an initial population of 2.23 log10 CFU/g,
      viable cells were not detected after 4 days at 30 degrees C or 7 days at 20
      degrees C; tolerance was greater in real mayonnaise than in reduced-calorie
      mayonnaise dressing stored at 5 degrees C. The tolerance of E. coli O157:H7
      inoculated at the highest population density (6.23 log 10 CFU/g) was less in
      reduced-calorie mayonnaise dressing than in real mayonnaise at all storage
      temperatures. In reduced-calorie mayonnaise dressing and real mayonnaise
      initially containing 2.23 log10 CFU/g, levels were undetectable after 28 and 58
      days at 5 degrees C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534085
TI  - Modification of kanamycin-esculin-azide agar to improve selectivity in the
      enumeration of fecal streptococci from water samples.
AB  - Kanamycin-esculin-azide agar was modified by increasing the concentration of
      sodium azide to 0.4 g liter-1 and replacing kanamycin sulfate with 5 mg of
      oxolinic acid liter-1. The modification, named oxolinic acid-esculin-azide (OAA)
      agar, was compared with Slanetz-Bartley and KF agars by using drinking water and
      seawater samples. The OAA agar showed higher specificity, selectivity, and
      recovery efficiencies than those obtained by using the other media. In addition,
      no confirmation of typical colonies was needed when OAA agar was used, which
      significantly shortens the time of sample processing and increases the accuracy
      of the method.

PMID- 8534086
TI  - Xylose-metabolizing Saccharomyces cerevisiae strains overexpressing the TKL1 and
      TAL1 genes encoding the pentose phosphate pathway enzymes transketolase and
      transaldolase.
AB  - Saccharomyces cerevisiae was metabolically engineered for xylose utilization. The
      Pichia stipitis CBS 6054 genes XYL1 and XYL2 encoding xylose reductase and
      xylitol dehydrogenase were cloned into S. cerevisiae. The gene products catalyze
      the two initial steps in xylose utilization which S. cerevisiae lacks. In order
      to increase the flux through the pentose phosphate pathway, the S. cerevisiae
      TKL1 and TAL1 genes encoding transketolase and transaldolase were overexpressed.
      A XYL1- and XYL2-containing S. cerevisiae strain overexpressing TAL1 (S104-TAL)
      showed considerably enhanced growth on xylose compared with a strain containing
      only XYL1 and XYL2. Overexpression of only TKL1 did not influence growth. The
      results indicate that the transaldolase level in S. cerevisiae is insufficient
      for the efficient utilization of pentose phosphate pathway metabolites. Mixtures
      of xylose and glucose were simultaneously consumed with the recombinant strain
      S104-TAL. The rate of xylose consumption was higher in the presence of glucose.
      Xylose was used for growth and xylitol formation, but not for ethanol production.
      Decreased oxygenation resulted in impaired growth and increased xylitol
      formation. Fermentation with strain S103-TAL, having a xylose reductase/xylitol
      dehydrogenase ratio of 0.5:30 compared with 4.2:5.8 for S104-TAL, did not prevent
      xylitol formation.

PMID- 8534087
TI  - Survival of, and induced stress resistance in, carbon-starved Pseudomonas
      fluorescens cells residing in soil.
AB  - We investigated the survival, cell length, and development of general stress
      resistance in populations of Pseudomonas fluorescens R2f and its rifampin
      resistant mutant, R2f Rpr, following exposure to carbon starvation conditions in
      liquid cultures and residence in two different soils, Flevo silt loam (FSL) and
      Ede loamy sand (ELS). In much the same way as was recently shown for P. putida
      KT2442, carbon-starved P. fluorescens R2f populations revealed enhanced
      resistance to otherwise lethal treatments, such as exposure to ethanol, high
      temperature, osmotic tension, and oxidative stress. A large population of
      nonculturable P. fluorescens R2f Rpr cells arose shortly after their introduction
      into ELS soil, whereas the formation of nonculturable cells was not observed in
      FSL soil. Also, the inoculant cell (based on immunofluorescence) and CFU counts
      decreased faster in ELS soil than in FSL soil. Introduction of carbon-starved
      instead of exponential-growth-phase R2f Rpr cells into ELS soil did not affect
      bacterial survival. The inoculant cell length decreased in soil, and no large
      differences in cell length in the two soil types were observed. Addition of
      glucose to ELS soil resulted in a stable cell length of R2f Rpr cells, whereas
      carbon-starved cells introduced into ELS soil remained small. Exponentially
      growing R2f Rpr cells developed enhanced resistance to ethanol, high temperature,
      osmotic tension, and oxidative stress within 1 day in both soils, whereas cells
      introduced into ELS soil amended with glucose showed decreased resistance. Cells
      that were carbon starved prior to introduction into ELS soil showed unchanged
      stress resistance levels upon residence in soil.

PMID- 8534088
TI  - Bioconversion of 2,4-diamino-6-nitrotoluene to a novel metabolite under anoxic
      and aerobic conditions.
AB  - Under nitrate-reducing, nongrowth conditions, a Pseudomonas fluorescens species
      reduced 2,4,6-trinitrotoluene to aminodinitrotoluenes, which were then further
      reduced to diaminonitrotoluenes. 2,4-Diamino-6-nitrotoluene (2,4-DANT) was
      further transformed to a novel metabolite, 4-N-acetylamino-2-amino-6-nitrotoluene
      (4-N-AcANT), while 2,6-diamino-4-nitrotoluene (2,6-DANT) was persistent. Efforts
      to further degrade 2,4-DANT and 2,6-DANT under aerobic, nitrogen-limited
      conditions were unsuccessful; 2,6-DANT remained persistent, and 2,4-DANT was
      again transformed to the 4-N-AcANT compound.

PMID- 8534089
TI  - Structure and function of Tn5467, a Tn21-like transposon located on the
      Thiobacillus ferrooxidans broad-host-range plasmid pTF-FC2.
AB  - A 3.5-kb region of plasmid pTF-FC2, which contains a transposon-like element
      designated Tn5467, has been sequenced, and its biological activity has been
      investigated. The transposon is bordered by two 38-bp inverted repeat sequences
      which have sequence identity in 37 of 38 and in 38 of 39 bp to the tnpA distal
      and tnpA proximal inverted repeats of Tn21, respectively. Within these borders,
      open reading frames with amino acid similarity to a glutaredoxin-like protein, a
      MerR regulatory protein, and a multidrug-resistant-membrane transport-like
      protein were found. The gene for the glutaredoxin-like protein was expressed in
      Escherichia coli and enabled growth of a glutathione-requiring E. coli trxA gshA
      mutant on minimal medium and the reduction of methionine sulfoxide to methionine.
      In addition, there were two regions which, when translated, had homology to 85%
      of the N-terminal region of the Tn21 resolvase (tnpR) and to 15% of the C
      terminus of the Tn21 transposase (tnpA). A region containing res-like sites was
      located immediately upstream of the partial tnpR gene. Neither the partial
      transposase nor the resolvase genes of Tn5467 were biologically active, but
      Tn5467 was transposed and resolved when the Tn21 transposase and resolvase were
      provided in trans. Tn5467 appears to be a defective transposon which belongs to
      the Tn21 subgroup of the Tn3 family.

PMID- 8534090
TI  - Cloning and expression of a novel toxin gene from Bacillus thuringiensis subsp.
      jegathesan encoding a highly mosquitocidal protein.
AB  - A gene, designated cry11B, encoding a 81,293-Da crystal protein of Bacillus
      thuringiensis subsp. jegathesan was cloned by using a gene-specific
      oligonucleotide probe. The sequence of the Cry11B protein, as deduced from the
      sequence of the cry11B gene, contains large regions of similarity with the Cry11A
      toxin (previously CryIVD) from B. thuringiensis subsp. israelensis. The Cry11B
      protein was immunologically related to both Cry11A and Cry4A proteins. The cry11B
      gene was expressed in a nontoxic strain of B. thuringiensis, in which Cry11B was
      produced in large amounts during sporulation and accumulated as inclusions.
      Purified Cry11B inclusions were highly toxic for mosquito larvae of the species
      Aedes aegypti, Culex pipiens, and Anopheles stephensi. The activity of Cry11B
      toxin was higher than that of Cry11A and similar to that of the native crystals
      from B. thuringiensis subsp. jegathesan, which contain at least seven
      polypeptides.

PMID- 8534091
TI  - A general method for the consecutive integration of single copies of a
      heterologous gene at multiple locations in the Bacillus subtilis chromosome by
      replacement recombination.
AB  - We have devised a two-step procedure by which multiple copies of a heterologous
      gene can be consecutively integrated into the Bacillus subtilis 168 chromosome
      without the simultaneous integration of markers (antibiotic resistance). The
      procedure employs the high level of transformability of B. subtilis 168 strains
      and makes use of the observation that thymine-auxotrophic mutants of B. subtilis
      are resistant to the folic acid antagonist trimethoprim (Tmpr), whereas thymine
      prototrophs are sensitive. First, a thymine-auxotrophic B. subtilis mutant is
      transformed to prototrophy by integration of a thymidylate synthetase-encoding
      gene at the desired chromosomal locus. In a second step, the mutant strain is
      transformed with a DNA fragment carrying the heterologous gene and Tmpr colonies
      are selected. Approximately 5% of these appear to be thymine auxotrophic and
      contain a single copy of the heterologous gene at the chromosomal locus
      previously carrying the thymidylate synthetase-encoding gene. Repetition of the
      procedure at different locations on the bacterial chromosome allows the isolation
      of strains carrying multiple copies of the heterologous gene. The method was used
      to construct B. subtilis strains carrying one, two, and three copies of the
      Bacillus stearothermophilus branching enzyme gene (glgB) in their genomes.

PMID- 8534092
TI  - Yeast succession in the Amazon fruit Parahancornia amapa as resource partitioning
      among Drosophila spp.
AB  - The succession of yeasts colonizing the fallen ripe amapa fruit, from
      Parahancornia amapa, was examined. The occupation of the substrate depended on
      both the competitive interactions of yeast species, such as the production of
      killer toxins, and the selective dispersion by the drosophilid guild of the amapa
      fruit. The yeast community associated with this Amazon fruit differed from those
      isolated from other fruits in the same forest. The physiological profile of these
      yeasts was mostly restricted to the assimilation of a few simple carbon sources,
      mainly L-sorbose, D-glycerol, DL-lactate, cellobiose, and salicin. Common fruit
      associated yeasts of the genera Kloeckera and Hanseniaspora, Candida
      guilliermondii, and Candida krusei colonized fruits during the first three days
      after the fruit fell. These yeasts were dispersed and served as food for the
      invader Drosophila malerkotliana. The resident flies of the Drosophila willistoni
      group fed selectively on patches of yeasts colonizing fruits 3 to 10 days after
      the fruit fell. The killer toxin-producing yeasts Pichia kluyveri var. kluyveri
      and Candida fructus were probably involved in the exclusion of some species
      during the intermediate stages of fruit deterioration. An increase in pH,
      inhibiting toxin activity and the depletion of simple sugars, may have promoted
      an increase in yeast diversity in the later stages of decomposition. The yeast
      succession provided a patchy environment for the drosophilids sharing this
      ephemeral substrate.

PMID- 8534093
TI  - Genetic diversity of Burkholderia solanacearum (synonym Pseudomonas solanacearum)
      race 3 in Kenya.
AB  - Genetic diversity among isolates of the bacterial plant pathogen Burkholderia
      solanacearum (synonym Pseudomonas solanacearum) race 3 biovar II of Kenya was
      determined by PCR with repetitive sequences (ERIC and BOX repetitive primer sets)
      and pulsed-field gel electrophoresis of genomic DNA digested by rare-cutting
      restriction endonucleases (RC-PFGE). The study comprised 46 isolates collected
      during 1992 from the major potato-growing regions of Kenya (45 were identified as
      race 3 biovar II, and 1 belonged to race 3 biovar N2) and 39 reference isolates
      from 19 other countries. RC-PFGE identified 10 distinct profile types among the
      Kenyan race 3 biovar II isolates (29 of the isolates exhibited identical
      profiles) and a further 27 distinct profile types among the reference isolates.
      ERIC and BOX primer sets were unable to differentiate race 3 biovar II isolates
      within the Kenyan population but differentiated a further two distinct profile
      types among the reference isolates. The race 3 biovar N2 isolate had a highly
      distinct RC-PFGE and repetitive sequence PCR profile. Statistical analysis of the
      data identified biogeographic trends consistent with conclusions drawn from
      previous studies on the origin and worldwide dissemination of race 3 biovar II
      isolates; however, genomic fingerprinting by RC-PFGE revealed a level of genetic
      diversity previously unrealized.

PMID- 8534094
TI  - Rapid differentiation of bacterial species with multiple probes of different
      lengths in a single slot blot hybridization.
AB  - We describe a highly efficient method for dot and slot blot hybridizations with
      multiple oligonucleotide probes for high throughput identification of organisms
      and studies of microbial community structures. Several probes with distinct
      specificities were designed to have the same melting temperature but unique
      lengths by adding different numbers of nonspecific nucleotides to one end. All of
      the probes were mixed, labelled with 32P, and hybridized to one piece of membrane
      on which genes coding for 16S rRNAs from different bacterial species had been
      immobilized. After hybridization, the bound probes were eluted and resolved on a
      denaturing polyacrylamide gel and the identities of the genes coding for 16S
      rRNAs were read from an autoradiograph of the gel. The results from the
      application of this technique to pure actinomycete cultures are reported here.

PMID- 8534095
TI  - Cloning and characterization of the genes for p-nitrobenzoate degradation from
      Pseudomonas pickettii YH105.
AB  - Pseudomonas pickettii YH105 was isolated for its ability to utilize p
      nitrobenzoate as the sole source of carbon, nitrogen, and energy. Degradation of
      p-nitrobenzoate by this strain proceeds through a reductive route as evidenced by
      the accumulation of ammonia in the culture medium during growth on p
      nitrobenzoate. Enzyme assays and high-performance liquid chromatography (HPLC)
      analysis of culture supernatants indicate that p-nitrobenzoate is degraded
      through p-hydroxylaminobenzoate and protocatechuate. In order to clone the genes
      responsible for the initial steps in the catabolic pathway, a cosmid library was
      constructed with P. pickettii YH105 genomic DNA. The library was screened for
      clones capable of transforming p-nitrobenzoate to protocatechuate, using a plate
      assay specific for diphenolic compounds. HPLC analysis of culture supernatants
      confirmed that the cosmid clones did indeed produce protocatechuate from p
      nitrobenzoate. Five positive cosmid clones that possessed this activity were
      identified. Restriction digests of the cosmid clones indicated that all of the
      clones had two EcoRI fragments in common (3.9 and 1.0 kb). One of these cosmid
      clones, designated pGJZ1601, was chosen for further analysis. Subcloning and
      activity assay experiments localized the genes responsible for the conversion of
      p-nitrobenzoate to protocatechuate to a 1.4-kb SalI-SphI DNA fragment. Further
      subcloning experiments localized the gene coding for p-nitrobenzoate reductase,
      responsible for the first enzymatic step in the catabolic pathway, to a 0.8-kb
      SalI-ApaI DNA fragment. The gene for the second step in the catabolic pathway,
      coding for hydroxylaminolyase, was located adjacent to the gene for the p
      nitrobenzoate reductase.

PMID- 8534096
TI  - Effect of point-of-use, activated carbon filters on the bacteriological quality
      of rural groundwater supplies.
AB  - The water quality of 24 rural, domestic groundwater supplies treated with point
      of-use, powdered activated carbon (PAC) filters was monitored to determine how
      such treatment might impact the bacteriological quality of private, residential
      drinking water supplies. Heterotrophic-plate-count (HPC) and total coliform
      analyses were performed on raw, PAC-treated, and overnight or stagnant (first
      draw) PAC-treated water samples. Densities of HPC bacteria were elevated by 0.86
      and 0.20 orders of magnitude for spring and well water systems, respectively, in
      PAC-treated effluents following overnight stagnation compared with levels in
      untreated treated effluents. Densities of HPC bacteria in PAC-treated effluents
      were significantly reduced (P < 0.01) below influent levels, however, after the
      point-of-use device was flushed for 2 min. While PAC significantly reduced the
      number of coliforms in product waters (P < 0.01), these indicator organisms were
      still detected in some effluents. Seasonal variations were evident in microbial
      counts from spring but not well water systems. It appears that aside from periods
      following stagnant-water use, such as overnight, PAC treatment does not
      compromise the bacteriological quality of drinking water obtained from
      underground sources.

PMID- 8534097
TI  - Direct detection of recombinant gene expression by two genetically engineered
      yeasts in soil on the transcriptional and translational levels.
AB  - The expression of a recombinant gene by yeasts seeded into soil samples was
      directly measured by analyzing transcripts and gene product occurrences in soil
      extracts. Two yeast species, Saccharomyces cerevisiae WHL292 and Hansenula
      polymorpha LR9-Apr4, both engineered by a synthetic gene sequence encoding the
      mammalian peptide aprotinin, produced and secreted this peptide in batch cultures
      at concentrations of 90 and 64 ng ml-1, respectively. In S. cerevisiae, the
      aprotinin gene was located on plasmid p707 and expressed constitutively. H.
      polymorpha carried the gene chromosomally integrated, and its expression was
      inducible by methanol. To detect aprotinin transcripts, cells were directly lysed
      in the soil samples and the crude lysates were hybridized to oligo(dT)-coated
      magnetized polystyrene beads (Dynabeads). After separation and purification in a
      magnetic field, aprotinin mRNA was detected by reverse transcriptase PCR with
      aprotinin gene-specific primers. Transcripts from 10 cells g of soil-1 were
      sufficient for detection. When 10(7) cells of S. cerevisiae were inoculated into
      soil, aprotinin mRNA was detectable during the first 4 days. Addition of methanol
      and a combined nutrient solution was necessary to induce aprotinin gene
      expression of H. polymorpha in soil. Aprotinin could be detected directly in soil
      extracts by an indirect enzyme-linked immunosorbent assay with monoclonal
      aprotinin-specific antibodies. The detection threshold was 45 pg g of soil-1. In
      presterilized soil inoculated with S. cerevisiae (10(6) CFU g-1), aprotinin
      accumulated during the first 10 days to 12 ng g of soil-1 and then remained
      constant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534098
TI  - Differentiation of epidemic-associated strains of Listeria monocytogenes by
      restriction fragment length polymorphism in a gene region essential for growth at
      low temperatures (4 degrees C).
AB  - The growth of Listeria monocytogenes in food stored in the cold has often been
      implicated in outbreaks of listeriosis. Many subtyping schemes have suggested
      that epidemic-associated strains belong to a unique genetic group. It has not yet
      been possible, however, to identify molecular or bacteriologic markers unique to
      epidemic-associated strains. Recently we cloned three genes of L. monocytogenes,
      ltrA, ltrB, and ltrC, which are essential for growth at low temperatures (4
      degrees C). The use of a 1.2-kb PstI fragment derived from ltrB as a probe in
      Southern blots of HindIII-digested DNA revealed three hybridization patterns: the
      first (a 5.0-kb band) was observed in strains of serotypes 4b, 1/2b, and 3b; the
      second (a 3.1-kb band) was seen in strains of serotypes 1/2a, 3a, 1/2c, and 3c;
      and the third (a 9.5-kb band) was characteristic of epidemic-associated serotype
      4b strains. These and other data suggest that probes derived from this gene
      region that is essential for growth at low temperatures can be useful molecular
      tools for the subtyping of strains implicated in food-borne listeriosis.

PMID- 8534100
TI  - Identification of two pigments and a hydroxystilbene antibiotic from Photorhabdus
      luminescens.
AB  - Two yellow pigments were isolated for the first time from the entomopathogenic
      bacterium Photorhabdus luminescens in liquid culture and were identified as the
      anthraquinone derivatives 3,8-dimethoxy-1-hydroxy-9,10-anthraquinone (minor) and
      1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (major). A known antibiotic, 3,5
      dihydroxy-4-isopropylstilbene, was also detected and for the first time showed
      strong fungicidal activity against several fungi of medical and agricultural
      importance.

PMID- 8534099
TI  - Cloning and DNA sequence analysis of two abortive infection phage resistance
      determinants from the lactococcal plasmid pNP40.
AB  - The lactococcal plasmid pNP40, from Lactococcus lactis subsp. lactis biovar
      diacetylactis DRC3, confers complete resistance to the prolate-headed phage phi
      c2 and the small isometric-headed phage phi 712 in L. lactis subsp. lactis
      MG1614. A 6.0-kb NcoI fragment of pNP40 cloned in the lactococcal Escherichia
      coli shuttle vector pAM401 was found to confer partial resistance to phi 712.
      Subcloning and deletion analysis of the recombinant plasmid pPG01 defined a 2.5
      kb ScaIHpaI fragment as conferring phage insensitivity. Sequence analysis of this
      region confirmed the presence of two overlapping open reading frames (ORFs).
      Further subcloning of pNP40 to characterize the resistance determinant active
      against phi c2 identified a 5.6-kb EcoRV fragment of pNP40 which, when cloned in
      pAM401, conferred partial resistance to both phi c2 and phi 712. Subcloning and
      deletion analysis of the recombinant plasmid pCG1 defined a 3.7-kb EcoRV-XbaI
      fragment as encoding phage insensitivity. DNA sequence analysis of this region
      revealed the presence of a single complete ORF. The introduction of a frameshift
      mutation at the unique BglII site within this ORF disrupted the phage resistance
      phenotype, confirming that this ORF is responsible for the observed phage
      insensitivity. The mechanisms encoded by pPG01 and pCG1 in L. lactis subsp.
      lactis MG1614 conformed to the criteria defining abortive infection and were
      designated AbiE and AbiF, respectively. Analysis of the phage DNA content of phi
      712-infected hosts containing AbiF demonstrated that it inhibited the rate of
      phage DNA replication, while AbiE had little effect on phage DNA replication,
      suggesting a later target of inhibition. The predicted protein product of abiF
      shows significant homology to the products of two other lactococcal abortive
      infection genes, abiD and abiD1.

PMID- 8534101
TI  - Sequencing and analysis of the prolate-headed lactococcal bacteriophage c2 genome
      and identification of the structural genes.
AB  - The 22,163-bp genome of the lactococcal prolate-headed phage c2 was sequenced.
      Thirty-nine open reading frames (ORFs), early and late promoters, and a putative
      transcription terminator were identified. Twenty-two ORFs were in the early gene
      region, and 17 were in the late gene region. Putative genes for a DNA polymerase,
      a recombination protein, a sigma factor protein, a transcription regulatory
      protein, holin proteins, and a terminase were identified. Transcription of the
      early and late genes proceeded divergently from a noncoding 611-bp region. A 521
      bp fragment contained within the 611-bp intergenic region could act as an origin
      of replication in Lactococcus lactis. Three major structural proteins, with sizes
      of 175, 90, and 29 kDa, and eight minor proteins, with sizes of 143, 82, 66, 60,
      44, 42, 32, and 28 kDa, were identified. Several of these proteins appeared to be
      posttranslationally modified by proteolytic cleavage. The 175- and 90-kDa
      proteins were identified as the major phage head proteins, and the 29- and 60-kDa
      proteins were identified as the major tail protein and (possibly) the tail
      adsorption protein, respectively. The head proteins appeared to be covalently
      linked multimers of the same 30-kDa gene product. Phage c2 and prolate-headed
      lactococcal phage bIL67 (C. Schouler, S. D. Ehrlich, and M.-C. Chopin,
      Microbiology 140:3061-3069, 1994) shared 80% nucleotide sequence identity.
      However, several DNA deletions or insertions which corresponded to the loss or
      acquisition of specific ORFs, respectively, were noted. The identification of
      direct nucleotide repeats flanking these sequences indicated that recombination
      may be important in the evolution of these phages.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8534102
TI  - Statistical approach for comparison of the growth rates of five strains of
      Staphylococcus aureus.
AB  - The interaction of temperature (10, 14, 25, 31, and 37 degrees C), pH (pH 5, 5.6,
      6.5, 7.4, and 8), and NaCl (0, 2, 5, 8, and 10%) in a laboratory medium affects
      the specific growth of Staphylococcus aureus. From growth curves obtained by the
      turbidimetric technique, a nonlinear model in which the specific growth rate (mu)
      is fitted directly, without data transformation and with the residual error
      variations taken into account, is proposed. This model correctly fits
      experimental data and gives more biological information than the quadratic
      polynomial model. Moreover, the comparison of five strains of S. aureus was
      performed by a principal-component analysis in which the specific growth rate was
      the identifying characteristic for S. aureus strains. The results obtained from
      model coefficient comparison among the five strains and from multivariate data
      analysis allow the same classification of strains to be performed. Two of them
      have similar behaviors during food spoilage, two others could be distinguished by
      their capacity to grow at a low temperature, whereas the last one was markedly
      different from the others.

PMID- 8534103
TI  - Degradation and utilization of xylan by the ruminal bacteria Butyrivibrio
      fibrisolvens and Selenomonas ruminantium.
AB  - The cross-feeding of xyland hydrolysis products between the xylanolytic bacterium
      Butyrivibrio fibrisolvens H17c and the xylooligosaccharide-fermenting bacterium
      Selenomonas ruminantium GA192 was investigated. Cultures were grown anaerobically
      in complex medium containing oat spelt xylan, and the digestion of xylan and the
      generation and subsequent utilization of xylooligosaccharide intermediates were
      monitored over time. Monocultures of B. fibrisolvens rapidly degraded oat spelt
      xylan, and a pool of extracellular degradation intermediates composed of low
      molecular-weight xylooligosaccharides (xylobiose through xylopentaose and larger,
      unidentified oligomers) accumulated in these cultures. The ability of S.
      ruminantium to utilize the products of xylanolysis by B. fibrisolvens was
      demonstrated by its ability to grow on xylan that had first been digested by the
      extracellular xylanolytic enzymes of B. fibrisolvens. Although enzymatic
      hydrolysis converted the xylan to soluble products, this alone was not sufficient
      to assure complete utilization by S. ruminantium, and considerable quantities of
      oligosaccharides remained following growth. Stable xylan-utilizing cocultures of
      S. ruminantium and B. fibrisolvens were established, and the utilization of xylan
      was monitored. Despite the presence of an oligosaccharide-fermenting organism,
      accumulations of acid-alcohol soluble products were still noted; however, the
      composition of carbohydrates present in these cultures differed from that seen
      when B. fibrisolvens was cultivated alone. Residual carbohydrates present at
      various times during growth were of higher average degree of polymerization in
      cocultures than in cultures of B. fibrisolvens alone. Structural characterization
      of these residual products may help define the limitations on the assimilation of
      xylooligosaccharides by ruminal bacteria.

PMID- 8534104
TI  - Cloning, sequencing, and expression of a xylanase gene from the extreme
      thermophile Dictyoglomus thermophilum Rt46B.1 and activity of the enzyme on fiber
      bound substrate.
AB  - A genomic library of the Dictyoglomus sp. strain Rt46B.1 was constructed in the
      phage vector lambda ZapII and screened for xylanase activity. A plaque expressing
      xylanase activity, designated B6-77, was isolated and shown to contain a genomic
      insert of 5.3 kb. Subcloning revealed that the xylanase activity was restricted
      to a internal 1,507-bp PstI-HindIII fragment which was subsequently sequenced and
      shown to contain a single complete open reading frame coding for a single-domain
      xylanase, XynA, with a putative length of 352 amino acids. Homology comparisons
      show that XynA is related to the family F group of xylanases. The temperature and
      pH optima of the recombinant enzyme were determined to be 85 degrees C and pH
      6.5, respectively. However, the enzyme was active across a broad pH range, with
      over 50% activity between pH 5.5 and 9.5. XynA was shown to be a true endo-acting
      xylanase, being capable of hydrolyzing xylan to xylotriose and xylobiose, but it
      could not hydrolyze xylobiose to monomeric xylose. XynA was also shown to
      hydrolyze xylan present in Pinus radiata kraft pulp, indicating that it may be of
      use as an aid in pulp bleaching. The equivalent xylanase gene was also isolated
      from the related bacterium Dictyoglomus thermophilum, and DNA sequencing showed
      these genes to be identical, which, together with the 16S small-subunit rRNA gene
      sequencing data, indicates that Rt46B.1 and D. thermophilum are very closely
      related.

PMID- 8534105
TI  - Detection of small round structured viruses in shellfish by reverse transcription
      PCR.
AB  - We describe the application of a previously developed sample extraction procedure
      to the detection of small round structured viruses (SRSVs) in shellfish. Initial
      seeding experiments showed that PCR inhibitor removal and virus recoveries were
      comparable to those in previous studies with poliovirus. Shellfish from a range
      of sewage-contaminated sites were then tested for the presence of SRSVs by using
      broadly reactive PCR primers followed by Southern blotting with internal probe
      sites. Positive results were obtained from 5 of 31 field samples tested. Four of
      these positive samples were from highly polluted sites. PCR product sequence
      analysis confirmed their identity as SRSV and showed sequence diversity compared
      with virus controls, suggesting that the results were not a consequence of PCR
      cross-contamination. Finally, shellfish associated with four separate outbreaks
      of viral gastroenteritis were tested by PCR and Southern blot for the presence of
      SRSVs. All outbreak samples tested gave positive results. As far as we are aware,
      this is the first demonstration of the detection in environmentally contaminated
      shellfish of the SRSVs responsible for human gastroenteritis. This development
      may help contribute to the further development of public health controls for
      molluscan shellfish.

PMID- 8534106
TI  - Aflavinines and other antiinsectan metabolites from the ascostromata of
      Eupenicillium crustaceum and related species.
AB  - This report describes the distribution of antiinsectan metabolites present in
      sclerotioid ascostromata produced by representative strains of Eupenicillium
      crustaceum and fungal taxa that are considered to be closely related. The hexane
      and chloroform extracts of E. crustaceum NRRL 3332 displayed significant
      antiinsectan activity in assays against the corn earworm, Helicoverpa zea. The
      major metabolite accounting for this antiinsectan activity was a known aflavinine
      analog, 10,23-dihydro-24,25-dehydroaflavinine, occurring at approximately 2.8
      mg/g of dry ascostromata. In dietary assays at ca. 3,000 ppm, a 79% reduction in
      weight gain and a 42% reduction in feeding rate were observed in H. zea and
      Carpophilus hemipterus larvae, respectively. A new aflavinine analog, 10,23,24,25
      tetrahydro-24-hydroxyaflavinine, was also identified. These aflavinine compounds
      are the first to be reported from a fungal genus other than Aspergillus. New
      macrophorin-type metabolites accounted for the antiinsectan activity of
      ascostromata produced by E. crustaceum NRRL 22307, which produced no aflavinines,
      while Eupenicillium molle NRRL 13062 produced both aflavinines and macrophorins.
      Sclerotia produced by Penicillium gladioli NRRL 938, NRRL 939, and QM 2743, a
      fungus reported to be conspecific with the anamorph of E. crustaceum, produced
      neither aflavinines nor macrophorins. Eupenicillium reticulisporum NRRL 3446
      produced the aflavinine analog 10,23-dihydro-24,25-dehydroaflavinine and an
      unrelated compound called pyripyropene A, a potent inhibitor of acyl-coenzyme A
      cholesterol acyltransferase. Eupenicillium abidjanum NRRL 5809, reported to be
      conspecific with E. reticulisporum, produced neither of these compounds. The
      Eupenicillium species that produced aflavinines are also known for their ability
      to grow rapidly with reduced water activity.

PMID- 8534107
TI  - Natural assemblages of marine bacteria exhibiting high-speed motility and large
      accelerations.
AB  - Natural communities of marine bacteria, an isolate (FMB-Bf3) from one marine
      community, and Escherichia coli were examined by video microscopy for the
      magnitude and uniformity of their speed. Natural communities formed tight
      microswarms that showed higher speeds (mean = 230 microns s-1) than did E. coli
      (15 microns s-1) or FMB-Bf3 (mean = 62 microns s-1). Outside the microswarms, the
      marine bacteria slowed to 45 microns s-1. Between turns, in mid run, and while
      travelling in straight lines, the natural-community bacteria accelerated up to
      1,450 microns s-2 while the cultured bacteria showed maximum accelerations of 70
      and 166 microns s-2. The frequency distribution of speed change for the marine
      bacteria was skewed towards a few large negative accelerations and a range of
      positive accelerations. The general pattern was one of relatively slow increases
      in speed followed by abrupt declines. The results indicate that the mechanical
      generation and energetic maintenance, as well as the environmental function, of
      bacterial motility need reappraisal. We conclude that the standard bacterial
      motility parameters of low and uniform speed, derived from culture-based studies,
      are not necessarily applicable to marine bacterial communities.

PMID- 8534108
TI  - Genome analysis of Clostridium botulinum type A by pulsed-field gel
      electrophoresis.
AB  - Genomic DNA from type A Clostridium botulinum was digested with restriction
      endonucleases that cut at rare sites, and the large fragments were separated by
      pulsed-field gel electrophoresis. Of 15 restriction enzymes tested, MluI, RsrII,
      SmaI, NruI, KspI, NaeI, and XhoI generated satisfactory digestion patterns of
      genomic DNA of various C. botulinum strains, enabling the use of the method for
      genomic fingerprinting. The genomes of four group I (type A) C. botulinum strains
      examined had similar restriction patterns. However, each strain had unique
      digestion patterns, reflecting genotypic differences. The genome size of C.
      botulinum strain 62A was estimated to be 4,039 +/- 40 kbp from the summation of
      restriction fragments from MluI, RsrII, and SmaI digestions. Genes encoding
      proteins involved in the toxinogenicity of C. botulinum, including neurotoxin,
      hemagglutinin A, and genes for a temperate phage, as well as various transposon
      Tn916 insertion sites in C. botulinum 62A, were mapped by pulsed-field gel
      electrophoresis. The genes encoding neurotoxin and hemagglutinin A-1, were
      located on the same fragment in several cases, indicating their probable physical
      linkage. The macrorestriction analysis established here should be useful for
      genetic and epidemiological studies of C. botulinum.

PMID- 8534109
TI  - In situ 31P nuclear magnetic resonance for observation of polyphosphate and
      catabolite responses of chemostat-cultivated Saccharomyces cerevisiae after
      alkalinization.
AB  - The proposed pH buffering and phosphagenic functions of polyphosphate were
      investigated by subjecting chemostat-cultivated Saccharomyces cerevisiae to
      alkalinization (NaOH addition) and anaerobiosis. The subsequent changes in
      intracellular phosphate-containing species were observed in situ by nuclear
      magnetic resonance (NMR) spectroscopy by using the NMR cultivator we developed.
      For the alkalinization experiments, changes in catabolite secretion were also
      measured in parallel experiments. Additionally, a range of potential
      neutralization capacity was investigated: a dilute culture and concentrated
      cultures with low or high polyphosphate content. The concentrated cultures
      displayed increased cytosolic pH and rapid polyphosphate degradation to small
      chains. The pH changes and extent of polyphosphate degradation depended inversely
      on initial polyphosphate content. The dilute culture restored extracellular pH
      rapidly and secreted acetate. The concentrated culture with low polyphosphate
      reserves also secreted acetate. In contrast to the alkalinization-induced
      polyphosphate dynamics, anaerobiosis resulted in the complete hydrolysis of
      polyphosphate to P(i), as opposed to small chains, and reduced cytosolic pH. The
      results and calculations suggest that the bulk of NMR-observable polyphosphate
      (vacuolar) degradation to short polymers conceivably contributes to neutralizing
      added alkalinity. In other circumstances, such as anaerobiosis, degradation
      serves other functions, such as phosphorylation potential regulation.

PMID- 8534110
TI  - Purification and characterization of an extracellular beta-1,4-mannanase from a
      marine bacterium, Vibrio sp. strain MA-138.
AB  - A beta-mannanase (EC 3.2.1.78) from Vibrio sp. strain MA-138 was purified by
      ammonium sulfate precipitation and several chromatographic procedures including
      gel filtration, adsorption, and ion-exchange chromatographies. The final ion
      exchange chromatography Mono Q yielded one major active fraction and three minor
      active fractions. The major active fraction was purified to homogeneity on the
      basis of native polyacrylamide gel electrophoresis (PAGE). This purified enzyme
      was identified as a glycoprotein by periodic acid-Schiff staining and a monomeric
      protein with a molecular mass of 49 kDa by sodium dodecyl sulfate-PAGE. The pI of
      the enzyme was 3.8. The purified enzyme exhibited maximal activity at pH 6.5 and
      40 degrees C and hydrolyzed at random the internal beta-1,4-mannosidic linkages
      in beta-mannan to give various sizes of oligosaccharides. The first 20 N-terminal
      amino acid sequence of the purified enzyme showed high homology with the N
      terminal region of beta-mannanase from Streptomyces lividans 66.

PMID- 8534111
TI  - Purification and partial amino acid sequence of plantaricin S, a bacteriocin
      produced by Lactobacillus plantarum LPCO10, the activity of which depends on the
      complementary action of two peptides.
AB  - Plantaricin S, one of the two bacteriocins produced by Lactobacillus plantarum
      LPCO10, which was isolated from a green-olive fermentation (R. Jimenez-Diaz, R.M.
      Rios-Sanchez, M. Desmazeaud, J.L.Ruiz-Barba, and J.-C. Piard, Appl. Environ.
      Microbiol. 59:1416-1424, 1993), has been purified to homogeneity by ammonium
      sulfate precipitation, by binding to SP-Sepharose fast-flow, phenyl-Sepharose CL
      4B, and C2/C18 reverse-phase chromatographies. The purification resulted in a
      final yield of 91.6% and a 352,617-fold increase in the specific activity. The
      bacteriocin activity was associated with two distinct peptides, termed alpha and
      beta, which were separated by C2/C18 reverse-phase chromatography. Although beta
      alone appeared to retain a trace of inhibitory activity, the complementary action
      of both the alpha and beta peptides was required for full bacteriocin activity,
      as judged by both the agar well diffusion and the microtiter plate assays. From
      the N-terminal end, 26 and 24 amino acids residues of alpha and beta,
      respectively, were sequenced. Further attempts at sequencing revealed no
      additional amino acids residues, suggesting that either modifications in the next
      amino acid residue blocked the sequencing region or that the C-terminal end had
      been reached. The amino acid sequences of alpha and beta show no apparent
      homology to each or to other bacteriocins purified from lactic acid bacteria.

PMID- 8534112
TI  - Purification and properties of xylanase A from alkali-tolerant Bacillus sp.
      strain BP-23.
AB  - Xylanase A from the recently isolated Bacillus sp. strain BP-23 was purified to
      homogeneity. The enzyme shows a molecular mass of 32 kDa and an isoelectric point
      of 9.3. Optimum temperature and pH for xylanase activity were 50 degrees C and
      5.5 respectively. Xylanase A was completely inhibited by N-bromosuccinimide. The
      main products of birchwood xylan hydrolysis were xylotetraose and xylobiose. The
      enzyme was shown to facilitate chemical bleaching of pulp, generating savings of
      38% in terms of chlorine dioxide consumption. The amino-terminal sequence of
      xylanase A has a conserved sequence of five amino acids found in xylanases from
      family F.

PMID- 8534113
TI  - The beta-lactamase secreted by the antarctic psychrophile Psychrobacter immobilis
      A8.
AB  - A class C beta-lactamase has been purified from the culture supernatant of the
      antarctic psychrophile Psychrobacter immobilis A8. This psychrophilic beta
      lactamase displays a low level of thermal stability and a low optimal temperature
      of activity. In contrast to other cold-adapted enzymes, its level of specific
      activity is not higher than that of mesophilic class C beta-lactamases.

PMID- 8534114
TI  - Mutations in the trpD gene of Corynebacterium glutamicum confer 5
      methyltryptophan resistance by encoding a feedback-resistant anthranilate
      phosphoribosyltransferase.
AB  - The trpD gene from tryptophan-hyperproducing Corynebacterium glutamicum ATCC
      21850 was isolated on the basis of its ability to confer resistance to 5
      methyltryptophan on wild-type C. glutamicum AS019. Comparative sequence analysis
      of the genes from the wild-type AS019 and ATCC 21850 trpD genes revealed two
      amino acid substitutions at the protein level. Further analysis demonstrated that
      the trpD gene product from ATCC 21850, anthranilate phosphoribosyltransferase,
      was more resistant to feedback inhibition by either tryptophan or 5
      methyltryptophan than its wild-type counterpart. It is proposed that
      phosphoribosyltransferase insensitivity to tryptophan in ATCC 21850 contributes
      to an elevated level of tryptophan biosynthesis.

PMID- 8534115
TI  - Cloning, sequencing, and expression in Escherichia coli of the Bacillus pumilus
      gene for ferulic acid decarboxylase.
AB  - The Bacillus pumilus gene encoding a ferulic acid decarboxylase (fdc) was
      identified and isolated by its ability to promote ferulic acid decarboxylation in
      Escherichia coli DH5 alpha. The DNA sequence of the fdc gene was determined, and
      the recombinant enzyme produced in E. coli was purified and characterized.

PMID- 8534116
TI  - Distribution and properties of fructosyl amino acid oxidase in fungi.
AB  - Fructosyl amino acid oxidase, and enzyme that can be used for the determination
      of glycated proteins in blood samples from diabetic patients, was used to screen
      cultures in our microorganism culture collection. Fructosyl amino acid oxidase
      was found only in the strains of four genera of fungi, Aspergillus, Fusarium,
      Gibberella, and Penicillium and exhibited different substrate specificities
      against fructosyl valine and N epsilon-fructosyl N alpha-Z-lysine. A fructosyl
      valine-specific enzyme from Penicillium janthinellum AKU3413 was monomeric (M(r),
      49,000), was most active at 35 degrees C and pH 8.0, and had a covalently bound
      flavin adenine dinucleotide as a prosthetic group.

PMID- 8534117
TI  - Alkalophilic Bacillus sp. strain LG12 has a series of serine protease genes.
AB  - Four tandem subtilisin-like protease genes were found on a 6,854-bp DNA fragment
      cloned from the alkalophilic Bacillus sp. strain LG12. The two downstream genes
      (sprC and sprD) appear to be transcribed independently, while the two upstream
      genes (sprA and sprB) seem to be part of the same transcript.

PMID- 8534118
TI  - Arginine deiminase system and acid adaptation of oral streptococci.
AB  - Streptococcus rattus FA-1 and Streptococcus sanguis NCTC 10904 underwent
      phenotypic acid adaptation in batch cultures toward the end of sugar-fueled
      growth after the culture pH had dropped to triggering values. The bacteria could
      be derepressed or induced for arginine deiminase independently of acid
      adaptation, and arginolysis afforded protection against acid killing over and
      above that of acid adaptation.

PMID- 8534119
TI  - Substrate diversity and expression of the 2,4,5-trichlorophenoxyacetic acid
      oxygenase from Burkholderia cepacia AC1100.
AB  - Burkholderia cepacia AC1100 uses the chlorinated aromatic compound 2,4,5
      trichlorophenoxyacetic acid as a sole source of carbon and energy. The genes
      encoding the proteins involved in the first step (tftA and tftB [previously
      designated tftA1 and tftA2, respectively]) have been cloned and sequenced. The
      oxygenase, TftAB, is capable of converting not only 2,4,5-trichlorophenoxyacetic
      acid to 2,4,5-trichlorophenol but also a wide range of chlorinated aromatic
      phenoxyacetates to their corresponding phenolic derivatives, as shown by whole
      cell and cell-free assays. The rate of substrate utilization by TftAB depends
      upon the extent of chlorination of the substrate, the positions of the chlorines,
      and the phenoxy group. These results indicate a mechanistic similarity between
      TftAB and the 2,4-dichlorophenoxyacetic acid/alpha-ketoglutarate-dependent
      dioxygenase, TfdA, from Alcaligenes eutrophus JMP134. The promoter of the
      oxygenase genes was localized by promoter-probe analysis, and the transcriptional
      start site was identified by primer extension. The beta-galactosidase activity of
      the construct containing the promoter region cloned upstream of the beta
      galactosidase gene in the promoter-probe vector pKRZ-1 showed that this construct
      is constitutively expressed in Escherichia coli and in AC1100. The -35 and -10
      regions of the oxygenase genes show significant sequence identity to typical
      Escherichia coli sigma 70 promoters.

PMID- 8534120
TI  - Development of a sensitive chemiluminometric assay for the detection of beta
      galactosidase in permeabilized coliform bacteria and comparison with fluorometry
      and colorimetry.
AB  - We developed a chemiluminometric assay of beta-galactosidase in coliform
      bacteria, using a phenylgalactose-substituted 1,2-dioxetane derivative as a
      substrate. Permeabilization of cells is required to ensure the efficient cellular
      uptake of this compound. By this method, one coliform seeded in 100 ml of sterile
      water can be detected after a 6- to 9-h propagation phase followed by a 45-min
      enzyme assay in the presence of polymyxin B. Compared with fluorometry and
      colorimetry, chemiluminometry afforded 4- and 1,000-fold increases in sensitivity
      and 1- and 6-h increases in the speed of detection, respectively.

PMID- 8534121
TI  - Detection of viable Cryptosporidium parvum oocysts by PCR.
AB  - PCR was used to detect and specifically identify a gene fragment from
      Cryptosporidium parvum. An 873-bp region of a 2,359-bp DNA fragment encoding a
      repetitive oocyst protein of C. parvum was shown to be specifically amplified in
      C. parvum. An excystation protocol before DNA extraction allowed the
      differentiation between live and dead Cryptosporidium parvum oocysts.

PMID- 8534122
TI  - Phylogenetic diversity of subsurface marine microbial communities from the
      Atlantic and Pacific oceans.

PMID- 8534123
TI  - Extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma--the
      Dusseldorf and Munich experience.
AB  - Extracorporeal photopheresis (ECP) using UVA irradiation of enriched lymphocytes
      in the presence of 8-methoxypsoralen as a photoactivatable substrate was
      originally introduced as a therapeutic regimen for cutaneous T-cell lymphoma
      (CTCL). Whereas ECP has previously been reported to be useful primarily for
      erythrodermic lymphoma, our purpose was to obtain data on safety and efficacy of
      ECP in patients suffering from different stages of CTCL. We report on 17
      patients, 3 with erythroderma and 14 with plaque or tumor stages. In contrast to
      other studies our patients were treated predominantly with ECP alone; only a few
      patients received concomitant therapy. These data have not been published
      previously, except for preliminary data on four patients. Of the 17 patients, 12
      (70%) responded to ECP. In seven patients at least 50% of skin lesions
      disappeared (defined as partial response) and in five patients at least 25% of
      skin lesions disappeared (defined as minor response). In two patients the disease
      remained stable and in three patients the disease progressed under the ECP
      treatment. No complete remission was observed. Partial responses were achieved
      not only in patients with early CTCL (stage Ib) but also in those with far
      progressed tumours (stage IVa). After treatment for 6 months partial responders
      showed an increase in the number of NK cells in their peripheral blood (P <
      0.01). We cannot confirm a relationship between this treatment and CD8 cell
      counts, as reported by others. Overall, our results indicate that ECP is a safe
      and effective regimen for the treatment of all stages of CTCL.

PMID- 8534125
TI  - Lesional elastase activity in psoriasis. Diagnostic and prognostic significance.
AB  - Human leukocyte elastase, a neutrophil-derived serine protease, is present in
      psoriatic lesions in an enzymatically active form. Our purpose was to assess the
      significance of human leukocyte elastase determinations in estimating the
      inflammatory activity of psoriatic lesions. A standardized method was used to
      analyse lesional elastase activity. Elastase activities were correlated with
      erythema, induration and hyperkeratosis of psoriatic lesions in 54 patients.
      Lesional elastase activities were also determined during treatment with salt
      water bathing and UVB irradiation. Lesional elastase activity correlated with
      skin induration and was inversely correlated with hyperkeratosis of the lesions.
      Psoriatic lesions with high elastase activity responded well to therapy, whereas
      lesions with low elastase activity appeared to be comparatively resistant. This
      study shows that by quantitative determination lesional elastase activities it is
      possible to distinguish predominantly inflammatory from predominantly
      hyperproliferative psoriasis. The latter shows delayed responsiveness to topical
      therapy with salt-water bathing plus UVB irradiation.

PMID- 8534124
TI  - Functional defect in cells involved in Langerhans cell histiocytosis.
AB  - The characteristic cell type involved in Langerhans cell histiocytosis, 'LCH
      cells', express most of the enzyme histochemical and immunocytochemical markers
      of normal epidermal Langerhans cells. It is not known, however, whether these LCH
      cells express the functional characteristics of normal epidermal Langerhans
      cells. We studied the alloantigen-presenting activity of LCH cells derived from
      lesional sites of three patients with the disease. Lesional cells expressing the
      CD1a molecule were enriched using either fluorescein-activated cell sorting or
      negative selection with indirect immunomagnetic beads, and functional activity
      was assessed using the 6-day primary allogeneic mixed-cell reaction. Compared to
      epidermal Langerhans cells from healthy controls, LCH cells showed minimal
      alloantigen-presenting activity on a per-cell basis. The diminished activity was
      not reversed by exogenous prostaglandin synthetase inhibitor or recombinant human
      IL-1 beta. This study confirms our previous report of a child, with fatal
      multisystem Langerhans cell histiocytosis suggesting that this disease represents
      a condition in which functionally defective cells of Langerhans cell phenotype
      accumulate and/or proliferate in various tissues. We postulate that the
      functional defect is a primary defect of these LCH cells that have acquired an as
      yet-undetermined biological insult(s).

PMID- 8534126
TI  - Ultrastructural localization of binding sites of sera from patients with linear
      IgA bullous dermatosis.
AB  - The localization of the antigen recognized by IgA basement membrane zone (BMZ)
      antibodies from patients with linear IgA bullous dermatosis (LABD) has not been
      established. The aim of our study was to find out the binding sites for IgA-BMZ
      antibodies in LABD in adults and children and, for comparison, the binding sites
      for IgA antibodies in IgA cicatricial pemphigoid (IgA-CP). Our series comprised
      21 sera from adult LABD, 4 sera from childhood LABD, and 2 sera from IgA-CP. The
      studies were performed using the sodium chloride split-skin method and indirect
      immunoelectron microscopy (IEM) with the use of the pre-embedding
      immunoperoxidase technique on two substrates: monkey oesophagus and normal human
      skin. Of the 27 sera, 24 reacted with the epidermis (19 from adult, 4 from
      childhood LABD and 1 from IgA-CP) and at the electron microscopic level labelled
      the upper part of the lamina lucida (LL) and/or hemidesmosomes, and 2 reacted
      with the dermis (1 from typical adult LABD and 1 from IgA-CP) and labelled the
      sublamina densa (SLD) region. Two sera were negative in IEM. In conclusion, the
      study indicated that the localization of the antigens is similar in adult and
      childhood LABD, and in IgA-CP.

PMID- 8534127
TI  - Photoageing-associated mitochondrial DNA length mutations in human skin.
AB  - It has recently been suggested that mitochondrial DNA (mtDNA) mutations are
      important contributors to human ageing and degenerative diseases. Using PCR
      techniques, we demonstrated three types of mtDNA length mutations, a 4977 bp
      deletion, a 7436 bp deletion and tandem duplications, in normal human skin
      tissues. We found that these mutations started to appear in the third decade of
      life, and the age at which the mutations could be detected in sun-exposed skin
      was usually younger than in non-exposed skin. Moreover, the incidences of these
      deletions and tandem duplications of mtDNA in sun-exposed skin were all
      significantly higher than those in non-exposed skin (P < 0.05). The 4977 bp
      deletion was the most prevalant mtDNA mutation in human skin, and the 7436 bp
      deletion was the least frequent among the three types of mtDNA mutations
      examined. We first demonstrated the existence of tandem duplications with sizes
      of about 260 bp, 200 bp and 150 bp in the D-loop region of mtDNA in the skin of
      elderly individuals. Among the three tandem duplications, the 200-bp duplication
      was found to occur most frequently in ageing skin. The tandem duplications were
      found to coexist with either or both of the deletions in some elderly
      individuals. The frequency of occurrence of mtDNA deletions and tandem
      duplications in skin was found to increase in an age-dependent manner. However,
      the incidence of tandem duplications was not well correlated with the age of the
      subject.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534128
TI  - No evidence of human papillomavirus DNA in actinic keratosis.
AB  - Human papillomaviruses (HPVs) are involved in premalignant and malignant skin
      diseases as well as in a variety of benign cutaneous and mucosal lesion disease.
      Its association with HPV infection has recently been evaluated in a few studies,
      but the results are contradictory. For further assessment of the role of HPVs in
      AK, a series of 100 paraffin-embedded biopsy specimens taken from subjects with
      AK were studied for the presence of HPV types 1, 2, 3, 4, 5, 7, 12, 15, 26, 36,
      37 and 59 DNA using in situ hybridization (ISH) under high stringency conditions
      (Tm -10 degrees C). All specimens were definitely negative for all bion specimens
      were definitely negative for all biotinylated HPV DNA probes tested. One fifth of
      the specimens were studied using the polymerase chain reaction (PCR) with general
      primers to confirm the negative results. All cases were also in the PCR. Our
      results suggest that HPVs are not directly involved in the aetiology of AK.

PMID- 8534129
TI  - Leukocyte proliferation in vitro against cottontail rabbit papillomavirus in
      rabbits with persisting papillomas/cancer or after regression.
AB  - Leukocyte proliferation responses to cotton-tail rabbit papillomavirus (CRPV)
      were measured in vitro with fresh whole blood as well as with ammonium chloride
      lysis-separated leukocytes. The antigens used were (1) CRPV particles produced in
      the athymic( (nu/nu) mouse xenograft system and (2) purified bacterial fusion
      proteins of the CRPV major and minor capsid proteins L1 and L2. CRPV-infected
      domestic rabbits with persistent papillomas or after papilloma regression, as
      well as uninfected controls were studied. There was a clearcut difference between
      infected and uninfected animals. We demonstrated antigen-specific leukocyte
      proliferation to at least one CRPV antigen in 12 of 21 infected rabbits but there
      was no positivity in 9 control animals (P = 0.004). There was whole-blood
      reactivity preferentially to intact CRPV particles in regressors. Specific but
      weak leukocyte proliferation against CRPV particles was detected in 6 of 9
      regressor rabbits (66%) but only in 1 of 12 progressors (8%; P = 0.0158). This
      trend of greater reactivity to intact CRPV particles in regressors as compared
      with progressors was not seen with peripheral blood leukocytes isolated by
      ammonium chloride lysis. We conclude that specific leukoproliferative responses
      against capsid CRPV proteins exist in rabbits experimentally infected with CRPV.

PMID- 8534130
TI  - Keratinocytes modulate the biosynthetic phenotype of dermal fibroblasts at a
      pretranslational level in a human skin equivalent.
AB  - In this study we investigated the influence of keratinocytes on the phenotype of
      fibroblasts in an in vitro human skin equivalent. Keratinocytes were seeded at
      the surface of fibroblast-populated mechanically restrained type I collagen gels
      (lattices). Lattices without keratinocytes were handled in parallel as controls.
      After 2 and 4 days in culture, the keratinocyte layer was removed and the steady
      state level of the mRNA for the main extracellular matrix macromolecules and
      interstitial collagenase produced by the fibroblasts was measured by Northern and
      dot blot analysis. A 50% decrease in the amount of procollagen type I and type
      III mRNAs was observed after 2 and 4 days of coculture while collagenase gene
      expression was upregulated by 300% when compared with control lattices. No
      significant modulation of type IV and type VI collagen, elastin or laminin B1
      mRNA levels was found. Fibronectin mRNA levels in fibroblasts were significantly
      increased only on day 4. All the observed changes could be reproduced using a
      conditioned medium collected from a lattice covered with keratinocytes added to a
      lattice containing fibroblasts alone. These results indicate that in an in vitro
      reconstituted skin, keratinocytes are able to modulate the biosynthetic phenotype
      of fibroblasts at a pretranslational level through a paracrine signalling
      pathway.

PMID- 8534131
TI  - Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma
      after topical application of 5-aminolevulinic acid: implications for photodynamic
      treatment.
AB  - Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell
      carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic
      acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX
      (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated
      with visible light in the 400-640 nm range. To evaluate variability and
      heterogeneity in PpIX production by tumors in such trials, and to assess the
      usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence
      distribution in BCC after topical application of 20% ALA cream. ALA cream was
      applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4
      h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo
      photography, ex vivo video fluorescence imaging, and fluorescence microscopy.
      External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo
      imaging, correlated with the clinical presence of BCC. Examination by a digital
      imaging fluorescence microscope revealed inter- and intratumor fluorescence
      variability and heterogeneity. PpIX fluorescence corresponding to full tomor
      thickness was found in six superficial and four nodular tumors, and partial
      thickness fluorescence was observed in five nodular tumors, but no PpIX
      fluorescence was observed in some areas of superficial, nodular and infiltrating
      tumors. In a significant number of nodular and infiltrating BCCs, topical ALA
      appeared to provide little or no PpIX in deep tumor lobules. In addition, no
      selectivity for tumor tissue versus normal epidermis was seen. The grossly
      brighter external PpIX fluorescence over tumors may be due, therefore, to
      enhanced penetration through tumor-reactive stratum corneum and to the tumor
      thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534132
TI  - Evaluation of topical retinoids for cutaneous pharmacological activity in Yucatan
      microswine.
AB  - The pharmacological effects of retinoids on skin have been studied primarily in
      test systems using small animals, such as mice and rabbits. Because of
      potentially significant differences in skin permeation and metabolism between
      small animals and humans, we have used Yucatan microswine as an alternative model
      for testing topical retinoids. Microswine skin resembles human skin, functionally
      and anatomically, more closely than most other species. In these studies,
      microswine skin was treated topically with retinoids for 5 consecutive days per
      week for 5 weeks. We found microswine epidermis to be functionally responsive to
      retinoids in that it undergoes hyperplasia and shows an increase in
      transepidermal water loss (TEWL). All-trans-retinoic acid, and its analogs, 13
      cis-retinoic acid, 4-hydroxy-retinoic acid and 4-oxo-retinoic acid all caused
      epidermal thickening and increased TEWL. The three analogs were less potent than
      all-trans-retinoic acid. A synthetic retinoid, TTNPB, potently induced epidermal
      hyperplasia and increased TEWL, but a close structural analog, m-carboxy-TTNPB,
      which is also inactive on nuclear retinoic acid receptors, was without effects on
      microswine epidermis. These findings show that microswine are useful for
      evaluating the cutaneous effects of topical retinoids. This model could be of
      value in identifying retinoids with potential clinical activity.

PMID- 8534133
TI  - Modulatory effects of selenium and strontium salts on keratinocyte-derived
      inflammatory cytokines.

PMID- 8534134
TI  - Hair cycle-dependent changes in mast cell histochemistry in murine skin.

PMID- 8534135
TI  - Biophysical monitoring of melanogenesis as a tool for pigment and hair research.

PMID- 8534136
TI  - Content of the different lipid classes in psoriatic scale.

PMID- 8534137
TI  - Adhesion molecules on the human mast cell line HMC-1 are upregulated during cell
      activation.

PMID- 8534138
TI  - [A very generous man].

PMID- 8534139
TI  - [Tissue levels of some elements in hyperthyreosis in rabbits].
AB  - The aim of the present study was to estimate the concentration of Cu, Zn, Mg, Ca
      in the following tissues: brain, heart, lung, liver, kidney and femoral muscles
      in conditions of experimentally induced hyperthyreosis. In general, in state of
      hyperthyreosis the concentration of all elements was considerably higher compared
      to euthyreosis. However, there are a few exceptions. Liver and heart tissue
      possessed higher concentration of Zn and Cu and kidney of Cu in euthyreosis.

PMID- 8534140
TI  - The effect of 5-aminosalicylic acid, hydrocortisone and indomethacin on gamma
      interferon induced expression of HLA-DR antigens on colonic epithelium.

PMID- 8534141
TI  - The somatostatin effect on the turnover of serotonin after the stimulation and
      blocking of the histamine H2 receptor in the rat's brain.

PMID- 8534142
TI  - Enkephalinase (EC 3.4.24.11)--neutral endopeptidase (NEP)--characterization,
      distribution and role in the human gastrointestinal tract.

PMID- 8534143
TI  - The role of posttraumatic intracranial cysts in the pathogeny of late epileptic
      seizures as exemplified by two patients.
AB  - Intracranial cysts are most often found in the lateral sulcus between the
      cerebral hemispheres and at the midline in the posterior cranial cavity. Covered
      with the clear or turbid arachnoidea, they are filled with a clear, colorless or
      slightly yellow cerebrospinal fluid, sometimes they have a considerable size and
      tend to be an unexpected discovery during an operation for symptoms of a brain
      tumor. The symptoms depend on the cyst's location and size. These are: headaches,
      epileptic seizures, sometimes deficiency signs. Located in the posterior cranial
      cavity they can imitate a cerebellar tumor (1, 3, 5). Intracranial cysts can be a
      result of abnormal ontogenesis or sometimes following a head injury (2). Since
      there is little information in literature on the incidence of posttraumatic
      intracranial cysts and their clinical picture, we find it desirable to present
      patients treated at Neurology Clinic of the Medical Academy in Lublin. All
      patients underwent a neuropsychological examination.

PMID- 8534144
TI  - Diagnostic difficulties in etiology of the lesion of peripheral neuron of the
      facial nerve during the growth of sialoma.
AB  - There are varied causes of lesions of the facial nerve: 75% of them is idiopathic
      paralysis or Bell paralysis (1), then there are injuries, diseases of the ears
      (otitis media and externa, otic zoster) and carcinomas of neuron VII,
      cerebellopontine angle tumors, tumors of the pons, of the petrosal bone, the
      middle ear, leukemias, diabetes, tumors of the salivary gland (2, 3, 4).
      Especially careful diagnosing is required for the cases of the lesions of the
      peripheral neuron n. VII, where, despite conventional treatment, there is no
      distinct improvement or where it is necessary to determine the right
      etiopatogenic factor among several possible ones. The patient under observation
      merits particular attention because it is necessary to determine the underlying
      cause of the lesion of the peripheral neuron of the facial nerve.

PMID- 8534145
TI  - Neuropsychological analysis of the consequences of intracerebral haematoma with
      frontal localization.

PMID- 8534146
TI  - The effect of intravenous loading with glucose on inorganic phosphorus and lipids
      bound phosphorus content in the patients with transient brain ischaemia.

PMID- 8534147
TI  - [The value of some imaging techniques in diagnosing diseases of mandibular
      articulation].

PMID- 8534148
TI  - Influence of lead acetate on the histological, ultrastructural and histochemical
      picture of the livers of albino rats.
AB  - The amount of lead pollution in the environment is increasing proportionally to
      the development of industry. Lead is capable of damaging the organism in many
      ways due to its high affinity to various tissues, different enzymes and serum
      proteins and its tendency to cumulate (1, 14). Acute lead poisoning occurs in
      people who have had intense, but short-term contact with organic lead compounds
      (tetraethylolead) used as an antidetonant in motor fuels, or plumbous
      orthoplumbate (red lead), which is an important component in anticorrosive paints
      (4, 6). Chronic poisoning by lead and lead salts, which used to occur in printers
      and workers in battery factories, is now a threat to the whole human population
      because of the hundreds of thousands of tons of tetraethylolead used as a fuel
      additive. This substance pollutes not only the atmosphere, but also the soil and
      the water and because of this, the food (10). The toxic effects of lead on the
      central and peripheral nervous system and the hematopoetic system is well known
      (9, 12), Less clear, however, are the toxic effects of this metal on the liver.
      As of now, there are still different views on the existence of negative effects
      of lead on the livers of people and animals exposed to this metal. Some
      researchers found no changes in the liver in cases of long-term contact with lead
      (3).

PMID- 8534149
TI  - The delta-aminolaevulinic acid level as an indication of lead contamination in
      school children.

PMID- 8534150
TI  - The estimation of the treatment of fractures of the bones of jaw with the use of
      miniplates.

PMID- 8534151
TI  - [Nitrogen compounds and their role in the contamination of the environment].
AB  - Nitrogen compounds occur in excess in the air, water, soil and food, which
      unfavourably affects human's health, causing a number of diseases. Toxic effect
      of nitrates and nitrites ought to be mentioned here in the first place. Nitrates
      and nitrites cause intoxications, specially of infants and of children,
      manifesting themselves by methemoglobinemia, anaemia and decreased content of
      vitamin A in the liver. Besides, nitrates and nitrites participate in the
      formation of strong nitrogen carcinogenic compounds, which may lead to stomach
      cancer. Due to big harmfulness of nitrogen compounds one should strive after
      lowering, minimizing their presence in the environment.

PMID- 8534152
TI  - [Histiocytosis X].
AB  - Histiocytosis X comprises a spectrum of diseases of unknown etiology in which
      localized or systemic histiocytic proliferations occur, often associated with
      eosinophilic infiltration of the involved tissues. The three clinical syndromes
      are: eosinophilic granuloma, Hand-Schuller-Christian disease and Abta-Letteres
      Siwesche's disease. Although diagnosis is based on the histochemical findings,
      the "definite" diagnosis requires the presence of Langerhans' granules in
      histiocytes. Localized histiocytosis X is treated by surgical excision and
      irradiation. Corticosteroid treatment is effective in symptomatic control in most
      patients and a variety of cytotoxic drugs have been used either alone or in
      combination with corticosteroids.

PMID- 8534153
TI  - [Traumatic hydrocephalus in children in CT images].
AB  - CT examinations were performed on 38 children who had suffered from perinatal
      trauma or a later injury. The recognised changes were classified as early or
      distant consequences of sustained head trauma. Special attention was paid to the
      time elapsing from the moment of injury to the occurrence of hydrocephalus and to
      the evolution of changes observed in the check-up CT examinations. The occurrence
      of zones of diminished periventricular density was correlated with the results of
      fluid drainage therapy. Atrophic changes of the cerebral nervous tissues were
      analysed in combination with the development of porencephalic traumatic fluid
      cavities.

PMID- 8534154
TI  - The role of CT-imaging in recognizing the type of hydrocephalus and porencephaly
      in children.
AB  - Intrauterine USG examination becomes more and more important in diagnosing
      developmental lesions of cerebral nervous tissue. However, CT-imaging is a method
      of choice, especially after parietal closure (13, 16). The character and etiology
      of porencephaly, congenital or acquired, is diversiform and often difficult to
      recognize (18). This paper presents an attempt at assessing different forms of
      porencephaly, taking into account congenital hydrocephalus in children by means
      of CT-imaging.

PMID- 8534155
TI  - [Evaluation of daunorubicin nephrotoxicity and effect of tocopherol and ascorbic
      acid on lesions induced in rat kidneys. I. Histologic, histochemical and
      biochemical studies].
AB  - Nephrotoxicity of daunorubicin in rats and effect of tocopherol and ascorbic acid
      on lesions induced in kidneys by daunorubicin were examined. Daunorubicin induced
      nephrotic syndrome with proteinuria and hypoproteinemia. Histological changes in
      the glomeruli appeared as a dilatation of capillary loops and enlargement of the
      urinary space. The glomerular basement membrane showed minimal thickening. In
      tubuli protein casts were noticed. No beneficial influence of tocopherol and
      ascorbic acid on daunorubicin related nephrotoxicity was observed.

PMID- 8534156
TI  - [Evaluation of daunorubicin nephrotoxicity and effect of tocopherol and ascorbic
      acid on lesions induced in rat kidneys. II. Ultrastructural studies of kidney
      glomeruli].
AB  - Nephrotoxicity of daunorubicin in rats and effect of tocopherol and ascorbic acid
      on lesions induced in kidneys by daunorubicin were examined. The most significant
      ultrastructural changes in the glomeruli included the loss of foot processes in
      visceral epithelial cells and appearance of microvillous and vacuolar formations.
      The glomerular basement membrane showed minimal thickening. No beneficial
      influence of tocopherol and ascorbic acid on daunorubicin related nephrotoxicity
      was observed.

PMID- 8534157
TI  - [Microscopic reconstruction of basilar artery wall in the rabbit].

PMID- 8534158
TI  - The effect of ethanol and coal dust on the tracheal mucosa--histochemical
      examinations of animals in experimental conditions.

PMID- 8534159
TI  - CT imaging of the brain lateral ventricular papillomas.

PMID- 8534160
TI  - [High molecular weight forms of aminoacyl-tRNA synthetases in animals. I. Amount
      and enzymatic composition of high molecular weight synthetase in cytosol from
      rabbit liver].
AB  - A high-molecular-weight complex composed of 15 amino acid-tRNA synthetases occurs
      in the rabbit liver cytosol apart from the free enzymes. The greatest activities
      in the complex are exhibited by lysyl- and arginyl-tRNA synthetases. The complex
      has the mass of about 4,000 kDa and the sedimentation constant about 19 S.

PMID- 8534161
TI  - [High molecular weight forms of aminoacyl-tRNA synthetases in animals. II. High
      molecular weight aminoacyl-tRNA synthetase complexes in lower animals].
AB  - High-molecular-weight aminoacyl-tRNA synthetase complexes have been found in hen,
      frog and carp liver cytosol as well as in cytosol from snails and Paramecium. The
      complexes from vertebrates and snails contained 13-15 aminoacyl-tRNA synthetases,
      revealed mass of about 4,000 kDa and sedimentation constant about 19 S. The
      complex from Paramecium containing 11 aminoacyl-tRNA synthetases, revealed a mass
      of about 1,600 kDa and sedimentation constant 15 S. The results of the present
      study support the view that the high-molecular-weight synthetase complexes are
      common entities in the animal kingdom.

PMID- 8534162
TI  - Morphological and histochemical research into the influence of the continuous
      administration of lead acetate on the microstructure of the male gonad in the
      white rat.

PMID- 8534163
TI  - The influence of encortone on changes of some parameters of parotid serous cells
      of female white rats of Wistar breed.

PMID- 8534164
TI  - The comparison of anticonvulsant properties of commercial diphenylhydantoin (DPH)
      and its 3-amino-derivative (3-amino-DPH).

PMID- 8534165
TI  - The medial root of the median nerve and its fascicles in man.

PMID- 8534167
TI  - Terminal divisions of the superior trunk of the brachial plexus.

PMID- 8534166
TI  - [Terminal divisions of the inferior trunk of the brachial plexus in man].
AB  - The thickness of terminal divisions of the inferior trunk, size of cross-section
      area of fascicles, number of fascicles and index of the fascicle's area have been
      examined bilaterally on the bodies of 69 men. The anterior division compared with
      the posterior division was 4.9 times thicker, the size of its cross-section area
      of fascicles was 4.1 times greater than in the posterior one. The index of
      fascicle's area was smaller by 16.3% in the anterior than in posterior division.
      The fascicles with the cross-section area up to 0.500 sq mm occurred more often
      in the anterior than in posterior division, and the fascicles with the cross
      section area greater than 0.5 sq mm occurred more often in the posterior one than
      in the anterior division. The studied features of the terminal parts of the
      inferior trunk, apart from the number of fascicles, underwent big changes during
      postnatal life, especially up to the 22nd year of life.

PMID- 8534168
TI  - [The inferior trunk of the brachial plexus in man].
AB  - The study was carried out on 137 trunks taken from the cadevers of 35 males and
      34 females who died between the age of 11 days and 86 years. A great individual
      variability and asymmetry regarding the thickness of the inferior trunk, number
      of fascicles, size of their cross-section area and the index of the fascicle's
      area was shown. The studied features of the trunk, apart from the number of
      fascicles, underwent big changes in postnatal life, especially between the age of
      1 and 14 years.

PMID- 8534169
TI  - Fascicular structure of the root of the brachial plexus from C8 in post fetal
      life in man.

PMID- 8534170
TI  - [Some routine test parameters of semen taken from the male partner of infertile
      couples and the state of the urogenital tract (prostate, seminal vesicles,
      testicles, epididymis) examined by ultrasound].
AB  - The authors investigated 214 men with endorectal and percutaneous scrotal
      sonography. These men were treated for the reason of sperm defects. The age range
      was 22 to 52 years. They were married for 2-10 years and infertile. The sperm was
      defected in respect of low percentage of motility (< or = 50%) and vitality and
      increased percentage of morphological abnormalities. The paper is an attempt to
      find the correlation between the sperm vitality and the frequency of prostate,
      seminal vesicles, testes and ejaculatory ducts defects. These correlations were
      particularly evident in sperm samples with decreased sperm concentration (1-20
      mln/ml). The authors suggested the usefulness of the finding in treating the male
      infertility.

PMID- 8534171
TI  - Radiological image of the femur after cementless total hip replacement in a 3
      years' follow-up.

PMID- 8534172
TI  - [The mechanism of the antitumor action of Bacillus intermedius ribonuclease].
AB  - In a concentration providing the maximum in vivo antitumor action, "Bacillus
      intermedius" RNAase had no in vitro cytotoxic effect on the cells of
      lympholeukosis NK/Ly. The enzyme did not inhibit the involvement of 3H-thymidine
      in the DNA biosynthesis in the tumor cells cultivated in vitro. A preliminary in
      vitro exposure of the cells to the enzyme did not influence their inoculation
      capacity. It was concluded that the mechanism of the enzyme antitumor action was
      not associated with the inhibition of the tumor cell viability. It was shown to
      be due to the activation of the intermediate effector system. The suggested
      mechanism of the mediated RNAse action on the tumor growth includes stimulation
      of the host immunity or removal/restriction of the tumor systemic action on the
      host.

PMID- 8534173
TI  - [The modification of Bacillus intermedius ribonuclease by urea derivatives].
AB  - The results of the "Bacillus intermedius" RNAase modification by urea derivatives
      are presented. The modifiers synthesized for that purpose were the following: N
      (4-chlorbenzoyl)-N'-benzolsulfonyl urea (M1) and N-(4-chlorbenzoyl)carbomoyl
      epsilon-aminocapronic acid (M2). It was shown that RNAase modified by M2
      stimulated the cell general metabolism by the test of the cell absorption of
      neutral red and had a more marked ability to disrupt RNA of the cell plasmatic
      membranes in comparison to that of the native enzyme.

PMID- 8534174
TI  - [The interferonogenic properties of yeast RNA-tilorone complexes in a cell
      culture].
AB  - The use of molecular complexes of yeast RNA with thyloron as inductors of type I
      interferons (alpha/beta-interferons) in the culture of cells L929 is described.
      It was shown that the complexes induced the interferon synthesis in the cells at
      the level comparable to that of the standard inductors of the polyribonucleotide
      nature i.e. larifan and poly(I)-poly(C). In the experimental doses the complexes
      proved to be nontoxic. It was concluded that the use of the yeast RNA and
      thyloron complexes as inductors in large-scale production of type I interferons
      was promising.

PMID- 8534175
TI  - [The efficacy of the emergency prophylactic and therapeutic actions of
      immunomodulators in experimental filovirus infections].
AB  - The study of the preventive and therapeutic action of some immunomodulators
      (ridostin, reaferon and polyribonate) used alone and in combinations was
      conducted on laboratory animals infected aerogenically by Marburg or Ebola virus.
      It was found that special preventive intranasal and intramuscular administration
      of ridostin provided protection of the animals infected by Marburg virus (p =
      0.1) and an increase in their mean lifespan by 2.4 days (p = 0.15). In the Ebola
      infection combined administration of ridostin and reaferon caused an essential
      increase in the mean lifespan of the animals by 2.9 days (p = 0.04). None of the
      tested drugs had any significant positive effect when used in various
      combinations according to the treatment schemes in Marburg and Ebola infections
      in guinea pigs.

PMID- 8534176
TI  - [The efficacy of the therapeutic and prophylactic actions of immunomodulators in
      experimental infection due to the causative agent of Venezuelan equine
      encephalomyelitis].
AB  - The investigation of the prevention and treatment action of some immunomodulators
      (ridostin, reaferon and polyribonate) used alone and in combinations was
      conducted on laboratory animals infected aerogenically by Venezuelan equine
      encephalitis (VEE) virus. A lower death rate of the aerogenically infected mice
      (10-30 respiratory LD50) was observed after intramuscular injection of ridostin.
      The preventive affect of ridostin and ridostin + reaferon administered
      intranasally and intramuscularly was achieved in the aerogenically infected
      guinea pigs (10 respiratory LD50). The results of the study on the early virus
      reproduction in the animals were used for the choice of the treatment scheme. The
      immunomodulators had no effect when the treatment was started 1 day after the VEE
      virus infection.

PMID- 8534177
TI  - [The characteristics of alirin B1--the basic component of a fungicidal
      preparation produced by the Bacillus subtilis 10-VIZR strain].
AB  - Alirin B1, the major active component of a fungicidal complex produced by
      Bacillus subtilis 10-VIZR was separated. Its physico-chemical and biological
      properties as well as the amino acid composition were investigated. Alirin B1 was
      shown to differ from the polypeptide substances described in the literature. The
      antibiotic was classified as belonging to the bacteriocins.

PMID- 8534178
TI  - [The technology of sewage purification and water treatment in self-contained
      oxidation-biosorption units].
AB  - A technological process for oxybiosorption of sewage was developed. The process
      and a self-contained unit using it are described.

PMID- 8534179
TI  - [The possibility for obtaining sorbents from the mycelial wastes of antibiotic
      production].
AB  - A technological process for production of a sorbent based on the mycelial waste
      of penicillin manufacture was developed. The process and its parameters are
      described. The exploitation conditions determine whether a strong sorbent with
      low sorption properties or a sorbent with higher sorption properties and lower
      granule strength is prepared.

PMID- 8534180
TI  - [A trial of using sulperazone (cefoperazone/sulbactam) in the combined treatment
      of patients with a burn infection].
AB  - The experience with the use of sulperazone (a combination of cefoperazone, a 3rd
      generation cephalosporin, and sulbactam, a beta-lactamase inhibitor, Pfizer, USA)
      in the treatment of 25 patients with burns and deep burns (1 to 85 and 1 to 70
      per cent of the body surface affection respectively) is described. The drug
      showed high clinical efficacy in the treatment of the infected burn wounds and
      infectious complications of the burns. Excellent and good results of the
      treatment were stated in 84 per cent of the patients. The extended affections and
      wound dissemination by multicomponent associations of polyresistant microbial
      strains lowered the microbiological efficacy of the treatment which amounted to
      58 per cent. Rapid development of resistance to the drug in staphylococci was
      noted. The tolerance of sulperazone was good. The side effects were observed only
      in 1 patient.

PMID- 8534181
TI  - [The interferon inducer neovir (kamedon) in the combined treatment of chronic
      inflammatory diseases of the adnexa uteri of chlamydial etiology (a clinical
      electron-microscopic study)].
AB  - One of the major factors of nonspecific immunity i.e. the state of the host
      interferon system was studied with a purpose of its correction in the treatment
      of inflammatory diseases of the uterine appendages of the chlamydial etiology. In
      all the female patients with chronic inflammatory diseases of the uterine
      appendages of the chlamydial etiology there was observed a disorder in the
      function of the interferon system link: a decrease in the concentration of blood
      serum interferon and a lower capacity of the blood cells to produce alpha- and
      gamma-interferons. The findings were used as a theoretical ground for the
      inclusion of neovir, an inductor of alpha-interferon to the treatment of such
      patients. After the completion of the treatment course with the use of neovir the
      index of the serum interferon proved to be higher than the normal by 2.4 log2IU
      and the indices of alpha- and gamma-interferons were lower than the normal only
      by 0.1 and 1.3 log2IU respectively. Therefore, the mechanism of the neovir action
      included activation of the function of the interferon endogenic system. The
      morphometrical analysis of the number of the cytoplasmic granules of the
      polymorphonuclear leukocytes in the peripheral blood before, during and after the
      therapy with neovir and pefloxacin showed that neovir not only promoted
      restoration of the digestion function of the neutrophilic leukocytes but also
      markedly activated it which provided a success of the phagocytic attack.

PMID- 8534182
TI  - [The molecular mechanisms of the multiple drug resistance of tumors].

PMID- 8534183
TI  - [The effect of norfloxacin on the luminol-dependent chemiluminescence and
      adhesion of leukocytes].
AB  - The in vitro effect of norfloxacin on the luminol-dependent chemiluminescence and
      adherence of polymorphonuclear leukocytes of guinea pigs was studied with the use
      of a wide range of the drug concentrations from 0.1 to 100 micrograms/ml under
      two different conditions, i.e. during the cell incubation in the presence of
      norfloxacin various concentrations and after the cell washing to remove the drug.
      In a concentration of 1 microgram/ml norfloxacin stimulated the zymosan-induced
      chemiluminescence. When the drug was used in a concentration of 10 micrograms/ml,
      the stimulating effect was less pronounced. In a concentration of 100 mu/ml
      norfloxacin significantly inhibited the leukocyte chemiluminescence. In
      concentrations of 0.1 to 100 micrograms/ml norfloxacin had no effect on the
      leukocyte adherence to the plastic surface covered by albumin.

PMID- 8534184
TI  - [Recent progress of the investigation of osteoclast].

PMID- 8534185
TI  - A case of advanced male breast cancer successfully treated by 5-fluorouracil,
      epirubicin and cyclophosphamide chemotherapy combined with tamoxifen.
AB  - A 79-year old male advanced breast cancer patient with metastases in lymph nodes,
      bones and anterior chest wall was effectively treated by a combination of
      chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide), tamoxifen and
      minor surgery. Two months after five cycles of chemotherapy, all lymph node
      swellings disappeared. The main breast cancer and the chest wall metastatic
      nodule were resected under local anesthesia. He was maintained on tamoxifen alone
      and showed no lymph node recurrence during the follow up period of 20 months,
      suggesting good control of bone metastatic lesions.

PMID- 8534186
TI  - Cavernous lymphangioma of the breast: case report of an infant.
AB  - Ultrasonography and magnetic resonance imaging (MRI) were used to assess a 4
      month-old male infant with a multicystic tumor of the left breast that was
      identified at birth. The tumor was removed surgically following the diagnosis of
      a cavernous hemangioma. Only seven similar cases of lymphangioma of the breast
      have been reported. We review these cases in conjunction with our own findings.

PMID- 8534187
TI  - Cronkhite-Canada syndrome: epidemiological study of 110 cases reported in Japan.
AB  - One hundred and ten cases of Cronkhite-Canada Syndrome (C-C-S) reported in Japan
      were reviewed in this epidemiologic study. Seventy-five percent of all C-C-S
      cases reported in the world in literature have been reported from Japan. There
      has been no special occupation associated with an increased incidence of C-C-S.
      Mental and physical stress have been confirmed as among the most important risk
      factors for this syndrome. Hypogeusia is the dominant initial symptom which
      usually is followed by diarrhea and ectodermal changes including alopecia, nail
      dystrophy and skin pigmentation. Gastrointestinal polyposis is closely related to
      the malabsorption which induced these ectodermal changes. However, there is a
      small number of cases in which alopecia precedes to the diarrhea in the disease
      course.

PMID- 8534188
TI  - The changing nature of ambulatory rehabilitation programs and services in a
      managed care environment.
AB  - Rehabilitation providers have been experiencing the impact of managed care on
      their services for many years. However, the outpatient, or ambulatory, segments
      of rehabilitation and their inpatient counterparts are being reshaped differently
      by this payment source. Because most ambulatory patients do not originate from an
      inpatient setting, managed care contracts directly with providers rather than
      flowing contracts through the hospital setting. Thus, ambulatory rehabilitation,
      more than other elements of the rehabilitation industry, is dependent on
      contracting to ensure patient flow.

PMID- 8534189
TI  - Toward a pediatric subacute care model: clinical and administrative features.
AB  - Subacute care, like our health care system generally, is designed primarily to
      meet the needs of the adult patient. Emphasis on the adult patient, however,
      ignores the children who could be appropriately and cost-effectively treated at a
      subacute level of care. These children offer the most persuasive argument yet for
      broadening our perspective on subacute care beyond the adult model, but to do so
      means considering the special needs of children, particularly in the areas of
      family-centered and age-appropriate care. In this article, we draw upon
      experience at 2 pediatric subacute care facilities to (1) identify specific
      treatment programs for children; (2) identify essential features of program
      delivery; (3) discuss how the typical adult-centered model needs to be modified
      for children; and (4) offer amendments that make the current adult-centered
      definitions of subacute care more responsive to children's needs.

PMID- 8534190
TI  - Subacute care: evolution in search of value.
AB  - The postacute continuum of nonhospital-based services has experienced rapid
      growth over the past decade because of a variety of economic factors. Medicare's
      prospective payment system for inpatient hospital stays combined with the
      diagnostic requirements of patients in acute medical rehabilitation and the
      growth of managed care have all reinforced the development of alternative levels
      and venues of care. Market forces are leading to consolidation and integrated
      health delivery systems offering both acute and postacute service options. The
      cost-effectiveness of these new models indicates promise for increased value
      measured by comparing resource utilization with outcomes. Reimbursement of the
      developing continuum, however, offers little incentive for efficiency. This
      article discusses the present dynamics of postacute growth and examines the
      issues that should be evaluated to determine its relevance in the spectrum of
      care.

PMID- 8534191
TI  - Measuring outcomes in the postacute continuum.
AB  - Measuring outcomes across the postacute continuum presents both practical and
      technical challenges. It requires capturing a variety of information across
      multiple therapeutic disciplines and care settings. While this information is
      collapsed into a single patient record, the ability to assess the contribution of
      each component to the overall outcome must be retained. Current health care data
      systems tend to fragment the information into discrete stays. Extant outcome
      instruments are perceived as being insensitive to change in noninpatient
      settings. The technology exists to correct shortcomings in both the information
      and the outcome assessment systems. The latter difficulties are the more complex,
      but by understanding the relationship between the measuring instrument and what
      it measures, and by properly matching the instrument to the level of the patient
      and the goals of the treatment program, many obstacles to effective outcomes
      management in the postacute continuum can be overcome. In a time of rapid change
      and experimentation in health care, however, outcomes managers must recognize
      that negative outcome data can result from ineffective programs as well as
      inappropriate instruments.

PMID- 8534192
TI  - An interview with David Bradley and Scott Fassbach.

PMID- 8534193
TI  - The role of the rehabilitation physician in the postacute continuum.
AB  - Compared to just 10 years ago, the US health care terrain looks much different
      today. In 1985, hospitals were the hub of a bustling delivery system that focused
      on acute care services and undervalued primary or preventive care. Health
      insurance benefits created incentives for consumers to use hospitals where their
      care was fully reimbursed, and discouraged office visits for which there were
      hefty copayments. Today, admissions into acute care hospitals are screened by
      none other than those same primary care physicians. These gatekeepers often have
      more authority over patient services and referrals than do the specialists and
      the hospitals. Financial incentives have made a 180 degrees shift, now motivating
      consumers to use outpatient care and office visits to satisfy the majority of
      their health care needs. Moreover, there are currently health care providers
      actively delivering a wide range of treatments and services that were not
      available or "covered" a decade ago. The migration of treatment out of hospitals
      into the vast frontier of postacute care has revolutionized our thinking about
      how patients receive treatment, in what locations, and by whom. This article
      describes the trends in financing and in clinical innovation that have
      contributed to the expansion of postacute alternatives. The factors that most
      clearly contribute to new opportunities facing rehabilitation physicians in
      postacute care are discussed, as are the added competencies required of those who
      choose to take a leadership role in the postacute delivery system. A case study
      of one model "managed care system" where the rehabilitation specialists are
      driving the care is presented. The future for rehabilitation specialists who are
      positioned to participate in setting the standards for high-quality postacute and
      chronic care in a future marketplace dominated by managed care is discussed.

PMID- 8534194
TI  - Review of the toxicology of beclomethasone dipropionate.
AB  - This paper reviews the published toxicity of beclomethasone dipropionate (BDP).
      BDP is a synthetic glucocorticosteroid which has a powerful local anti
      inflammatory effect but little systemic action. It has been developed for both
      dermatological and inhaled applications. LD50 values and other acute studies
      indicated low toxicity. Findings published for repeat dose and reproductive
      toxicity studies embraced the known range of metabolic and physiological effects
      of glucocorticoids. For repeat dose studies, these included reduction in body
      weight gains, cushingoid syndrome in dogs, reductions in the numbers of
      lymphocytes and the weights of the tissues connected with the immune system, and
      hepatic glycogen deposition and fatty liver changes. In reproductive studies,
      there was an increase in the prevalence of cleft palate in mice and rabbits and
      in the number of dead foetuses, and ossification was retarded. Despite the route
      of administration, there was a general similarity of effects within and between
      species. All observations were characteristic of synthetic glucocorticoids and
      related to the intrinsic effects of these drugs.

PMID- 8534195
TI  - 2-Butoxyethanol autoprotection is due to resiliance of newly formed erythrocytes
      to hemolysis.
AB  - Pretreatment with a low dose of a toxic chemical protecting the animals from a
      subsequently administered lethal dose of the same chemical is called
      autoprotection. Autoprotection by model hepatotoxicants has been recently shown
      to be due to augmentation of cell division and tissue repair as well as an
      inherent resiliance of newly divided cells. The present studies were designed to
      investigate if an autoprotection model could be established in an extrahepatic
      tissue. The second objective was to test the hypothesis that inherent resiliance
      of newly divided cells is a major contributing mechanism for autoprotection.
      Female Sprague-Dawley rats (200-250 g) received a single administration of a
      moderately toxic but nonlethal dose (500 mg/kg, p.o.) 7 days prior to the
      administration of an LD90 dose (1500 mg/kg, p.o.) of the same compound. All rats
      receiving the initial protective dose are able to survive the lethal dose of
      butoxyethanol, in contrast to the death of those receiving the lethal dose alone.
      Following the administration of butoxyethanol, the hematocrit decreased from the
      normal 45% to 18% and by day 7, recovered to normal levels. Following the lethal
      challenge, hematocrit decreased to 13% in the naive rats, while decreasing only
      to 27% in rats receiving the protective dose, permitting animal survival.
      Administration of pyrazole to inhibit metabolism of butoxyethanol to butoxyacetic
      acid abolished autoprotection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534196
TI  - Effect of inhibitors and substrates on methyl mercury uptake by rat erythrocytes.
AB  - Methyl mercury (MeHg) uptake by isolated erythrocytes from rats was studied at 20
      degrees C. Inhibitors and substrates were used to test which transport system was
      involved in MeHg uptake. Ouabain and ATP were used to test the active transport
      system. Glycine was used to test system Gly. DL-Methionine was used to test
      system L. Cysteine was used to test the cysteine-facilitated transport system.
      The effects of Ca2+, Mg2+ and Na+ on MeHg uptake have been examined. MeHgCl and
      4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) were used to test C1- ion
      transport system. D-Glucose and cytochalasin B were used to test the facilitated
      diffusive D-Glucose transport system. Colchicine and vinblastine were used to
      test the microtubule system. Probenecid was used to test the organic acid
      transport system. Valinomycin was used to test the effect of the membrane
      potential on MeHg uptake. The results showed that MeHg uptake at 20 degrees C
      might be involved in the following transport systems: 1) an active transport
      system; 2) a cysteine-facilitated transport system; 3) a C1- ion transport
      system; 4) a facilitated diffusive D-glucose transport system; 5) an organic acid
      transport system. The transport systems for MeHg uptake were sensitive to the
      membrane potential.

PMID- 8534197
TI  - Benzo(a)pyrenediolepoxide-hemoglobin adducts and 3-hydroxy-benzo(a)pyrene urinary
      excretion profiles in rats subchronically exposed to benzo(a)pyrene.
AB  - The time profiles of benzo(a)pyrenediolepoxide (BaPDE)-hemoglobin (Hb) adduct
      formation and 3-hydroxybenzo(a)pyrene (3-OHBaP) urinary excretion were studied in
      male Sprague-Dawley rats exposed to daily benzo(a)pyrene (BaP) intraperitoneal
      doses of 1.25, 6.25, and 31.25 mumol/kg administered Tuesday to Friday for 4
      consecutive weeks. Blood was withdrawn weekly, on Tuesdays, prior to dosing.
      Twenty-four-hour urine samples were collected on Mondays (following 72 h without
      treatment) and Thursdays. Analytes were quantified by high performance liquid
      chromatography (HPLC)/fluorescence. Exposure to BaP resulted in the accumulation
      of BaPDE-Hb adducts, reaching an average of 1.2 +/- 0.3, 8.3 +/- 1.9, and 38.2 +/
      6.1 pmol/g Hb for the 1.25, 6.25, and 31.25 mumol/kg per day doses after 4 weeks
      of treatment. The expected saw tooth excretion profile of 3-OHBaP was observed,
      with peaks on Thursdays and troughs on Mondays, and showed a progressive rise on
      both Mondays and Thursdays. Increase in Monday values with time suggested a
      possible increase in BaP body burden during exposure. To verify this aspect
      further, the urinary excretion kinetic of 3-OHBaP following acute intraperitoneal
      dosing (31.25 mumol/kg) was determined. Urine samples were collected at frequent
      timed intervals for up to 164 h post-dosing. Two-step elimination was observed,
      the second step having a half-life of 25 h, presumably linked to the slow release
      of BaP accumulated in fatty tissues upon repeated treatment.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8534198
TI  - Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their
      mixture. IV. Determination of liver concentrations.
AB  - Groups of male Sprague-Dawley rats were administered orally the following
      chlorinated dibenzo-p-dioxins (CDDs) in corn oil/acetone (95/5; v/v): 30-60
      micrograms/kg 2,3,7,8-tetrachlorodibenzo-dioxin (tetra-CDD), 160-270
      micrograms/kg1,2,3,7,8-pentachlorodibenzo-p-dioxins (penta-CDD), 630-1249
      micrograms/kg 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 5000-8000
      micrograms/kg 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (hepta-CDD) or a mixture
      of the four homologues such that each was present in the mixture at one quarter
      of its dose as a single compound. Animals were killed at 2 and 8 days after
      dosing. Livers were immediately removed, and aliquots frozen in liquid nitrogen.
      Storage occurred at -80 degrees C until further use. About 0.2 g of each
      lyophilized rat liver was extracted, the extract purified by column
      chromatography and analyzed by GC/MS for CDD content. Results obtained suggest
      that the absorption of CDDs after oral administration decreases in the order of
      tetra-CDD > or = penta-CDD > hexa-CDD > hepta-CDD, indicating that the dose was
      an incomplete surrogate of exposure in parts I-III of this publication series
      (Stahl et al. 1992; Weber et al. 1992a,b). Moreover, data also support the notion
      that the pharmacokinetics of CDD mixtures at high doses are somewhat different
      from those expected based on single compound exposures. Our findings suggest that
      the intrinsic relative potency in terms of toxic equivalents (TEQ) of the higher
      chlorinated homologues is slightly greater (about a factor of 2) than suggested
      by Stahl et al.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534199
TI  - Foodstuffs and human blood contamination by the mycotoxin ochratoxin A:
      correlation with chronic interstitial nephropathy in Tunisia.
AB  - Ochratoxin A (OTA) has been detected in high amounts in human blood samples
      collected in nephrology departments in Tunisia from nephropathy patients under
      dialysis, especially those categorised as having a chronic interstitial
      nephropathy of unknown aetiology. These represent 12-26.1% of all chronic renal
      failure patients. To clarify the situation, food and blood samples were collected
      from nephropathy patients and controls, (with no familial case of nephropathy).
      The OTA assay showed very different scales of OTA food and blood contamination
      from 0.1 to 16.6 micrograms/kg and 0.1-2.3 ng/ml, respectively, in controls and
      healthy individuals and 0.3-46 830 micrograms/kg for food and 0.7-1136 ng/ml for
      blood in nephropathy patients. The disease seems related to OTA blood levels and
      food contaminations, since the control group was significantly different from the
      nephropathy group (p < 0.005) for both food and blood ochratoxin A contamination.
      Combined with data published already, the results emphasize the likely endemic
      aspect of this OTA-related nephropathy occurring in Tunisia and possibly in other
      countries of northern Africa. This nephropathy is very similar to Balkan endemic
      nephropathy.

PMID- 8534200
TI  - A direct involvement of the central nervous system in hypophagia and inhibition
      of respiratory rate in rats after treatment with O,O,S-trimethyl
      phosphorothioate.
AB  - O,O,S-Trimethyl phosphorothioate (OOS-TMP) is known to induce unique symptoms,
      which are characterized by hypophagia, progressive weight loss, and hypothermia.
      To determine whether there is the possibility of a causal relationship between
      these toxic symptoms and a direct action of OOS-TMP on the central nervous
      system, we investigated the development of these symptoms in Fischer 344 female
      rats after oral or intracerebral treatment with OOS-TMP. Oral administration of
      OOS-TMP at 20 mg/kg induced marked hypophagia, progressive weight loss and
      hypothermia. Moreover, inhibition of respiratory rate was observed immediately
      after treatment. It lasts during the entire experimental period. Profound
      hypothermia below 34 degrees C was observed more frequently in the rats, which
      became hypercapnic (PaCO2 > or = 50 mmHg). In contrast, administration of OOS-TMP
      at 20 mg/kg (as much as the oral dose) into the cerebral lateral ventricle
      succeeded in inducing hypophagia, progressive weight loss and lowered respiratory
      rates. On the other hand, by this route of administration, OOS-TMP at 20 mg/kg
      failed to induce hypothermia, hypercapnia and lung injury. The present results
      suggest that hypophagia and inhibitions of respiratory rate are attributable to
      the direct action of OOS-TMP on the central nervous system, while other symptoms
      are associated with lung injury.

PMID- 8534201
TI  - Production, characterization and application of monoclonal antibodies against the
      organophosphorus nerve agent Vx.
AB  - Two monoclonal antibodies (Vx-BB8 and Vx-EA11) to the chemical warfare agent Vx
      were produced and characterized. A competitive inhibition enzyme immunoassay was
      developed to detect Vx concentrations as low as 3.7 x 10(-7) - 3.7 x 10(-6) mol/l
      in biological samples. Vx-BB8 400 micrograms given intravenously immediately
      before 1 x LD95 Vx or 400 micrograms Vx-BB8 intraperitoneally 1.5 h-3 days before
      1 x LD95 Vx could protect all the tested mice from death.

PMID- 8534202
TI  - Bioaccumulation of water soluble aluminium chloride in the hippocampus after
      transdermal uptake in mice.
AB  - Normally, only very small amounts of ingested aluminium are absorbed and
      accumulated. Despite the percutaneous absorption of many drugs and chemicals, the
      skin has not been considered as a possible site at which aluminium could enter
      the body. Application of low aqueous concentrations of aluminium chloride
      (A1C1(3), 6H20) (0.025-0.1 micrograms/cm2) to healthy shaved Swiss mouse skin for
      130 days led to a significant increase in urine, serum and whole brain aluminium,
      especially in the hippocampus, compared to control animals. This percutaneous
      uptake and accumulation of aluminium in the brain was greater than that caused by
      dietary exposure to 2.3 micrograms per day in feed and water. In vitro studies
      demonstrated the passage of aluminium through viable mouse skin. This study shows
      for the first time that aluminium is absorbed through the skin of mice in vivo
      and this contributes to a greater body burden than does oral uptake.

PMID- 8534203
TI  - Low serum concentration of all-trans and 13-cis retinoic acids in patients
      treated with phenytoin, carbamazepine and valproate. Possible relation to
      teratogenicity.
AB  - All-trans retinoic acid deficiency resulting from ethanol's interference with the
      synthesis of all-trans retinoic acid from retinol was recently suggested to cause
      the malformations of the fetal alcohol syndrome. Phenytoin, carbamazepine and
      valproate, might be teratogenic because they lower the concentration of all-trans
      retinoic acid in serum, by inducing the enzyme systems in the liver responsible
      for the metabolism of the all-trans retinoic acid, or by other mechanisms. Here
      we show, that in patients given therapeutic doses of phenytoin, carbamazepine and
      valproate, serum all-trans and 13-cis retinoic acid concentrations are indeed
      significantly lowered. We propose that drugs with this ability should be
      considered as potential teratogens.

PMID- 8534205
TI  - [Occupational asthma].

PMID- 8534204
TI  - Use of dantrolene in experimental scorpion envenomation by Androctonus australis
      hector.
AB  - Hyperthermia and profuse perspiration are rarely absent in severe cases of
      scorpion envenomation. Based on these observations, the aim of this study was to
      determine the therapeutic effects of dantrolene, on experimental poisoning by the
      venom of Androctonus australis hector. Dantrolene is a directly acting muscle
      relaxant which lowers the body temperature in malignant hyperthermia. The results
      indicate that the early use of this drug raises the LD50 in experimentally
      poisoned mice. If these results are transposable to humans, dantrolene could be a
      useful therapeutic adjuvant.

PMID- 8534206
TI  - [Early effects of intravenous steroid therapy on cell recruitment in sputum of
      chronic asthmatics].
AB  - Steroid is the key drug in the asthma therapy but not well known to play the role
      on the airway inflammatory cells. We examined sputum cells of acute excerbated 11
      chronic adult asthmatics before and 2-3 hours after intravenous steroid and
      aminophylline therapy. There was no changes in the percent count of living cell,
      epithelial cell, metachlomatic cell, macrophage and neutrophil before and after
      treatment. Lymphocyte was 3.3 +/- 6.5% before and 2.6 +/- 2.0% after treatment.
      CD4 and CD25 double positive cell (CD4+/CD25+) was 0.7 +/- 0.5 and 1.2 +/- 0.9%
      and CD8+/CD25+ cell was 0.4 +/- 0.4 and 0.6 +/- 0.5% before and after treatment
      respectively. These changes were not significant. Eosinophil percent count did
      not decrease significantly but EG1+/EG2+ cell decreased from 6.7 +/- 7.8 to 4.3
      +/- 5.2% significantly (p < 0.05). In the light of no decrease of activated T
      lymphocytes (CD25+ cells), we concluded that failure of tissue eosinophil
      response to lymphokines might result in a decrease in activated eosinophil count.

PMID- 8534208
TI  - [Respiratory function in students who had asthma in childhood].
AB  - Students who had asthma in childhood can be divided into three groups: "asthma
      remission" group "asthma-relapsing" group and "non-asthma-remission" group. When
      we made inquiries about three different groups, the incidence of each group was
      58%, 27% and 15%, respectively. In order to determine if childhood asthma affects
      respiratory function in adulthood, we measured respiratory functions by
      spirometry in 26 students who had asthma in childhood, and in seven control
      students. There was no significant difference between students with childhood
      asthma and control students in terms of FEV1.0% of predicted value. However,
      students who had asthma in childhood had lower levels of V25/HT% of predicted
      value in comparison with control students. The effects of deep inhalation in the
      three groups were evaluated by determining the values of maximal expiratory flow
      at 40% (MEF40) of vital capacity from partial (P) and maximal (M) flow-volume
      curves. There was no difference between the remission group and the control group
      in the MEF40 M/P ratio. This suggests that childhood asthma may deteriorate
      respiratory functions in adulthood by remodeling of peripheral airways.

PMID- 8534207
TI  - [Nasal smear cytology in bronchial asthma: correlation of appearance and numbers
      of nasal smear mast cells, eosinophils or basophils and serum IgE antibodies to
      house dust mite in patients with bronchial asthma].
AB  - Nasal smear cytology was studied in pediatric patients with bronchial asthma with
      special reference with IgE RAST to house dust mite, Dermatophagoides
      pteronyssinus (Dp). Results obtained were as follows: (1) Numbers of eosinophils
      on the nasal smear correlated well with Dp RAST score, (2) mast cells were
      detected before Dp RAST becoming positive and appearance of eosinophils, (3)
      basophils appeared after detection of eosinophils and only in patients with nasal
      smear eosinophils. These results suggest that mast cells are the early marker for
      allergic inflammation and basophils and eosinophils appear in association with
      overt sensitization with house dust mite in house dust mite-sensitized asthmatic
      patients.

PMID- 8534209
TI  - [Interleukin 1 production by peripheral blood mononuclear cells of children with
      bronchial asthma in remission].
AB  - To analyse the change of the immunological response in the remission state of
      children with bronchial asthma, we studied the interleukin 1 (IL-1) production of
      peripheral blood mononuclear cells (PBMC) obtained from children with bronchial
      asthma sensitized by mite antigen. After PBMC were cultured for 24 hours with
      Dermatophagoides farinae (Df) or lipopolysaccharide (LPS), the PBMC-derived
      culture supernatant was estimated for IL-1 alpha and beta by enzyme-linked
      immunosorbent assay (ELISA). PBMC from some of subjects with active asthma
      produced IL-1 alpha and beta without any stimulation, but not those from controls
      or subjects in remission. IL-1 alpha and beta production of PBMC stimulated with
      Df was observed in all three groups, but IL-1 produced by subjects with active
      asthma was higher than that produced by subjects in the other two groups.
      Moreover, when PBMC were incubated with LPS, the secretion of both IL-1 alpha and
      beta was enhanced. PBMC from patients with active asthma produced both IL-1 alpha
      and beta in amounts comparable to those produced by PBMC from control subjects,
      but IL-1 production of PBMC from patients in remission was lower than in the
      other two groups. IL-1 beta production was about ten times as much as IL-1 alpha.
      Df-induced IL-1 production of PBMC from asthmatic patients sensitized by mite
      antigen, which was increased in the active state, was down-regulated in the
      remission state. Moreover, nonspecific stimuli such as LPS may induce the
      suppressive factors which down-regulate IL-1 production.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8534210
TI  - [Autoregressive analysis of variability in heart rate and blood pressure in
      asthmatic children--difference of severity].
AB  - Changes in ECG R-R intervals and blood pressure (lye and stand) were assessed by
      the autoregressive power spectral analysis method in 40 asthmatic children (age
      range: 2-16 years, mean +/- SD: 9.4 +/- 4.1 years). Significantly lower low
      frequency (LF: < or = 0.1 cycle/beat) power and high frequency (HF: 0.1-0.5
      cycle/beat) power of R-R intervals were detected in severe type. LF fluctuations
      in R-R intervals are known to be mediated by the parasympathetic nervous system
      and the beta-adrenergic nervous system, while HF fluctuations in R-R intervals
      are mediated by the parasympathetic nervous system, LF fluctuations in systolic
      blood pressure by the alpha-adrenergic nervous system. The results suggested
      parasympathetic nervous system disorder especially in severe asthmatic children.
      Thus, spectral analysis of variability in R-R intervals and blood pressure are a
      useful tool for quantifying autonomic nervous system activity.

PMID- 8534211
TI  - [An attempt of applying the image processing for the automatic estimation of
      sampled airborne pollen].
AB  - Development of techniques to rapidly and easily estimate an airborne pollen
      quantity is necessitated in order to make out a appropriate prescription for an
      allergy patient from medical clinical viewpoints, and in order to research a
      movement of allergen from medical basic viewpoint. The measurement of airborne
      pollen quantity required a large labour and time, because the amount of pollen
      grains is visually measured by naked eye. This paper, as a first step to estimate
      an airborne pollen quantity full-automatically, discuss techniques to measure the
      quantity of sampled airborne cedar pollen automatically and rapidly using the
      image processing techniques. As a result, the following facts are cleared.
      Automatic measurement is possible to some degree without any special image
      processing. It is important to eliminate a noise on image as blurs on basefilm
      for high accuracy measurement. The precision has improved fairly with level
      correction for image. Sharpening filter is the most appropriate process to
      improve the accuracy of automatic measurement of sampled airborne pollen. This
      filtering process has a merit that the operativeness is easy.

PMID- 8534212
TI  - [Studies on thromboxane B2 level in nasal lavage fluid after antigen challenge in
      patients with allergic rhinitis and guinea pig models].
AB  - Thromboxane A2 (TxA2) seems to play an important role in bronchial constriction
      and hypersensitivity in asthmatics. To study the role of TxA2 in allergic
      rhinitis, we investigated the levels of thromboxane B2 (TxB2), a stable
      metabolite of TxA2, in nasal lavage fluid from patients with allergic rhinitis
      and from actively sensitized guinea pigs after antigen challenge by
      radioimmunoassay (RIA). There was a significant (p < 0.05) rise in TxB2 levels
      soon after antigen challenge in nasal lavage fluid from both patients (36.4 +/-
      7.5 pg/ml, mean +/- SE) and models (55.6 +/- 21.8 pg/ml). In some of the patients
      and models, there was an dual rise in TxB2 in the 10 hours after antigen
      challenge. There was a significant (p < 0.03) correlation between the patients
      whose levels of TxB2 were re-elevated and them whose nasal airway resistance
      showed dual rises. These results suggest that TxA2 may contribute to the nasal
      obstruction in later phase in allergic rhinitis.

PMID- 8534213
TI  - [Effect of mao-bushi-saishin-to (MBST), a formula of Chinese medicines, on 48 hr
      homologous passive cutaneous anaphylaxis in rats].
AB  - We studied the effect of oral administration of the extracts from MBST and its
      component chinese plants, and 1-ephedrine on 48 hr homologous passive cutaneous
      anaphylaxis (PCA), and histamine- or serotonin-induced skin reaction in rats.
      Administration (100-1,000 mg/kg) of MBST 1 hr before antigen challenge dose
      dependently inhibited PCA. Skin reaction induced by histamine was also inhibited
      by this formula at 1,000 mg/kg 1 hr prior to the provocation in some degree. The
      inhibitory component of MBST of PCA was found to be Mao. Further examinations
      revealed that 1-ephedrine, which is contained in Mao in a large amount, did not
      substantially inhibit histamine- or serotonin-induced skin reaction. These
      results indicate that MBST has a significantly inhibitory activity on PCA, to
      which 1-ephedrine from Mao in the formula almost totally contributes, through the
      inhibition of chemical mediator release. Since MBST showed some inhibition of
      histamine-induced skin reaction, on which 1-ephedrine did not affect, it is
      suggested that some ingredient of MBST responsible for inhibition of PCA may be
      involved in addition to 1-ephedrine.

PMID- 8534214
TI  - [The detection of anti-cerebellar antibody western blot analysis in serum from a
      patient with Miller Fisher syndrome].
AB  - We here report a case of Miller Fisher syndrome (MFS) in which serum anti
      cerebellar antibody was detected by Western blot analysis. The 32-year-old male
      studied suffered from diplopia, gait ataxia and sensory disturbance in the distal
      portion of the upper limbs preceded by cold-like symptoms. Neurological
      examination on admission revealed that he had external ophthalmoplegia with
      bilateral ptosis, cerebellar ataxia and areflexia. A cerebrospinal fluid
      examination showed albuminocytologic dissociation with a protein concentration of
      60 mg/dl. Brain CT and MRI showed no significant abnormalities. The patient was
      diagnosed as MFS, and treated it with two sessions of immunoadsorption
      plasmapheresis (IAPP). After receiving IAPP therapy, the patient's neurological
      symptoms and signs were improved. Western blot analysis showed the existence of
      antibody directed against mouse cerebellum but not against mouse cerebrum, brain
      stem, and spinal cord in his serum, the level of which was decreased after the
      IAPP therapy. Serum anti-GQ1b antibody was also elevated. As far as we are aware,
      there have been no reports showing the existence of anti-cerebellar antibodies
      detected by Western blot analysis. Though the pathogenesis of MFS remains
      unclear, our findings suggest that anti-cerebellar antibody detected by Western
      blot analysis may be caused by cerebellar ataxia in MFS.

PMID- 8534215
TI  - Diurnal cycle of SO2 concentrations in Rijeka and its relation to maximum and
      average daily concentrations.
AB  - Continuous recording of SO2 concentrations at one site in Rijeka in the heating
      season has shown that in spite of geographic and climatic differences, the
      pattern of diurnal cycle of SO2 concentrations does not differ from that recorded
      in Zagreb and in other towns with a temperate climate. The pattern is
      characterized by two peaks: a higher one in the morning that represents daily
      maximum and a lower one in the afternoon that is a good approximation of daily
      mean. Accordingly, maximum and mean daily concentrations could be assessed by
      short-term samples collected over given periods (8-10 and 15-18 h). As the
      diurnal cycle of SO2 concentrations could be disturbed by changes in weather
      conditions, equations were developed and coefficients established for calculating
      correction factors for adjustment of the estimated daily maximum and mean
      concentrations from two samples of short duration. The equations developed in
      Zagreb proved to be also valid for Rijeka. Presumably, the procedure could be
      used in other towns in the temperate region after the pattern of diurnal cycle of
      SO2 concentrations has been verified and the coefficients necessary for
      calculating correction factors established.

PMID- 8534216
TI  - Total suspended particulate matter concentrations in Zagreb during the 1975-1993
      period.
AB  - Daily average mass concentrations of total suspended particulate matter were
      measured at three sampling sites in Zagreb, and evaluated for the period April
      1975-March 1993. Each sampling site represented a different town area
      (residential, business and administrative, industrial) with different traffic
      density and type of energent used for space heating. The time trends of
      concentration levels could, to a certain extent, be attributed to traffic flow
      modification in the vicinity of the sampling sites, introduction of natural gas
      in dwellings and degree of energy consumption influenced by the standard of
      living. Periodograms show a well pronounced seasonal dependence of total
      suspended particulate matter concentrations, with high concentrations during
      winters. Analysis of the results in respect to the European Community air quality
      limits (1) and the levels of other pollutants (SO2 and smoke) leads to the
      conclusion that particulates being a persistent permanent problem have become a
      major issue concerning ambient air pollution in Zagreb.

PMID- 8534217
TI  - The effects of air pollution on ventilatory lung functions.
AB  - The prevalence of chronic bronchitis was studied among female subjects aged 18-63
      years from three areas with different ambient air quality: Bakar and Krasica with
      SO2 concentrations above the WHO guideline and Viskovo where the SO2
      concentrations were below the guideline. The subjects were examined and
      administered a questionnaire. Differences in their ventilatory lung functions
      were tested and related to air quality. The subjects from the two regions to air
      quality. The subjects from the two regions with a higher pollution level had
      lower FVC and FEV1 values than those from the Viskovo region. However, no
      statistically significant differences in the prevalence of chronic bronchitis
      between the subjects from regions with different ambient air quality were found.
      The same applies to the occurrence of pathological restrictive ventilation
      disturbances. In the Krasica region the occurrence of pathological obstructive
      ventilatory disturbances was significantly higher than in the Viskovo and Bakar
      regions; a correlation between the duration of residence and ventilatory lung
      function was also observed.

PMID- 8534218
TI  - Monitoring of personal exposure to air pollutants. Subjects' experience.
AB  - Seventeen volunteers, employees of a scientific institute, were involved in the
      monitoring of personal exposure to lead and cadmium in the ambient air. Thirteen
      of them answered a questionnaire concerning own behavior and difficulties
      encountered while wearing a personal sampler. Most subjects admitted that wearing
      the sampler and especially the noise produced by the pump made them avoid certain
      activities. This confirms our earlier observations that the application of
      personal samplers for surveying exposure of the general population might be not
      only costly but also tedious and unreliable. Therefore modelling based on
      pollutant concentrations and time spent in basic microenvironments is recommended
      for assessing human exposure of large population groups along with personal
      monitoring of a limited group of reliable subjects to validate the model.

PMID- 8534219
TI  - [Distribution of polycyclic aromatic hydrocarbons in the environment and personal
      exposure].
AB  - Polycyclic aromatic hydrocarbons are products of incomplete combustion of organic
      compounds in the environment or a consequence of human activities. They can be
      found in all environmental media. Although they are present in rather low
      concentrations they have been receiving increasing attention lately. Some of them
      have been proven carcinogens and mutagens. Sensitive analytical methods that are
      presently available have made the monitoring of polycyclic aromatic hydrocarbons
      practicable. This paper is a review of their chemical structures, nomenclature
      and biological actions. Their distribution and levels in the environment are
      described, with special emphasis on the fate and behaviour of these compounds in
      the atmosphere, as well as on studies of personal exposure.

PMID- 8534220
TI  - [Formaldehyde in the environment and its effect on health].
AB  - The presence of formaldehyde in the environment is due to natural processes and
      to man-made sources. It is produced in large quantities and has varied
      applications. One of the most common uses is in urea-formaldehyde and melamine
      formaldehyde resins. There are several indoor environmental sources that can
      result in human exposure including furniture containing formaldehyde-based
      resins, building materials, paints, disinfectants, carpets etc. Emphasis is
      placed on indoor formaldehyde levels and on the ways of their reduction or
      elimination.

PMID- 8534221
TI  - [Anabolic steroid abuse and mental disorder].
AB  - The literature on the psychiatric aspects of anabolic steroids (AS) abuse in the
      United States is reviewed. Since the 1980s the use of AS has become prevalent
      among adults and adolescents who are concerned with muscle size and strength, and
      the abuse of these agents is regarded as a serious drug problem. Researchers
      noticed that illicit, high-dose use of AS may produce not only somatic adverse
      effects but behavioral changes. Several studies using psychometry and
      questionnaires suggested that characteristic psychological phenomena such as
      increased aggression and irritability may be observed in AS abusers. Although the
      evidence determining the addictive potential of AS is limited, some authors
      provide evidence that the long-term use of AS may lead to a mental disorder which
      meets the DSM-III-R criteria of psychoactive substance abuse. Detailed case
      reports of AS-induced mental disorders are scarce, but characteristic symptoms,
      particularly major mood disturbances, have been recognized. Violent crimes
      committed by abusers taking large doses of AS have also been highlighted. In
      these cases the dangerous behavior appears to have been induced by aggression,
      grandiosity, and rage. This review indicates that empirical data specifying
      psychiatric effects of AS are not sufficient at present, and more attention needs
      to be paid to trends in AS abuse in Japan.

PMID- 8534222
TI  - Effect of chronic ethanol on phospholipase A2- and C-activity in chick embryo
      brain, heart and liver.
AB  - The activities of phospholipase A2 (PLA2) and C (PLC) in subcellulal fractions
      from chick embryo brain, heart and liver were determined using the substrate 1
      palmitoy 1-2-N-(4-nitrobenzo-2-oxa-1, 3-diazole amino caproyl-phsphatidylcholine
      (NBD-PC), and the effect of chronic ethanol treatment on these activities was
      evaluated. PLA2 and PLC activities of each fraction were assayed by measuring
      release of N- (4-nitrobenzo-2-oxa-1, 3-diazole) amino caproic acid (NBD-caproic
      acid) and of 1-palmitoy 1-2-NBD amino caproyl glycerol (NBD-DG) from exogenous
      NBD-PC. The microsomal membrane fluidity was estimated from diphenylhexatriene
      anisotropy (gamma). Cytosolic, mitochondorial, and microsomal subcellular
      fractions were prepared by differential centrifugation of homogenates of the
      brain, heart, and liver. Microsomal subcellular fractions from the brain, heart
      and liver of ethanol treated chick embryo showed significantly higher PLA2 and
      PLC specific activities than did corresponding fractions from non-treated chick
      embryo. Mitochondrial subcellular fractions from the brain and heart of ethanol
      treated chick embryo also showed significantly higher PLA2 and PLC specific
      activities than the corresponding control fractions. Microsomal fractions from
      the brain and heart of ethanol-treated chick embryo decreased significantly the
      gamma than those of control. These results suggest that the change in the
      membrane fluidity is an apparent prerequisite for the changes of PLA2 and PLC
      activities.

PMID- 8534223
TI  - [Psychological problem due to long-term organic solvent abuse].
AB  - Organic solvent abuse in adolescents has become a serious social problem. One of
      the reasons for this is the relationship to juvenile delinquency, and another is
      that it leads to various clinical symptoms including disturbance of
      consciousness, hallucinations, fantasia and apathy. In this study, using a health
      questionnaire that is composed of 33 psychiatric and 29 physical items and the
      Rorschach Test, we investigated these symptoms and the psychodynamics of
      personality respectively. The principal component analysis obtained for the
      health questionnaire extracted four factors as follows: 1) feelings of general
      fatigue and somatic symptoms, 2) feelings of guilt and self blame, 3) low self
      esteem and withdrawal adaptation, and 4) unreasonable anxiety and sleeping
      disturbance. The results of Rorschach Test supported the loss of libido,
      disability of reality testing and ego vulnerability in organic solvent abusers.
      This research strongly suggests that apathetic or depressive mood in chronic
      organic solvent abusers relates with loss of drive.

PMID- 8534224
TI  - [Amotivational syndrome of chronic organic solvent abusers--neuropsychological
      study].
AB  - It is conceivable that many of chronic organic solvent abusers have shown
      "Amotivational Syndrome" that is often seen in marijuana abuse. This syndrome
      revealed various psychiatric symptoms such as diminution of ambition,
      productivity and motivation. However, the pathogenesis of this syndrome is not
      elucidated. In present study, we examined 31 patients who showed amotivational
      syndrome (AS) induced by chronic organic solvents abuse, using neuropsychological
      battery including Benton Visual Retention Test (BVRT) and Bender Gestalt Test
      (BGT). In BVRT, there was a differences between AS and controls in the items of
      number of errors, omission, distortion and misplacement. In BGT, each Figure's
      score except I and VIII has changed and total score was 43.25 (vs control;
      23.05), corresponding to 9-10 year old development in AS. These results suggest
      that organic solvent-induced AS is closely related with neurological and
      cognitive impairments in the central nervous system.

PMID- 8534225
TI  - Reductions in milk production after induced parturition in dairy cows from
      commercial herds in south-western Victoria.
AB  - The milk production of cows after induced parturition was compared with that of
      non-induced cows with similar calving dates, in 37 winter-calving, pasture-fed,
      commercial dairy herds in south-western Victoria. Parturition was induced when
      most cows were between 27 and 35 weeks of pregnancy. Milk production was compared
      for the lactation that commenced immediately after induction. The percentage of
      cows whose lactations were terminated less than 120 days after calving was
      increased by induction. Mean percentages for untreated and induced groups were
      3.0% and 5.4%, respectively. For cows with lactations of at least 120 days
      duration, lactation length was not affected by the prior induction of
      parturition. However, milk production during the subsequent lactation was 9.0%
      less in induced groups. Fat and protein concentrations were not substantially
      affected. The reduction in milk production was not affected by stage of pregnancy
      when cows were induced, but tended to be greater in herds that delayed milking of
      induced cows.

PMID- 8534226
TI  - Efficacy of dressings for killing larvae of the sheep blowfly.
AB  - Resistance to organophosphorus (OP) insecticides in the Australian sheep blowfly
      has decreased the larvicidal effectiveness of several popular products used as
      dressings for flystrike. Laboratory bioassays in which near full-size Australian
      sheep blowfly larvae were immersed in flystrike dressings at registered
      concentrations for times ranging from 5 to 180 s indicated that none of the
      products was completely effective in killing highly OP-resistant larvae. Several
      products performed poorly, even against a susceptible population. Effectiveness
      did not always reflect the concentration of active ingredient. For example, the
      products considered to be the most, and least effective overall, contained 0.036%
      propetamphos but were formulated very differently. Larvicidal efficacy is
      important in terms of minimising injury to stock but also in the management of
      insecticide resistance. In situations when the degree of resistance is known, it
      will be possible to make recommendations for the most cost-effective treatment of
      flystrike. In the meantime, there appears to be a clear advantage for woolgrowers
      to use a propetamphos-based flystrike jetting product to dress flystrike lesions.

PMID- 8534227
TI  - Bronchoalveolar lavage in horses: effect of exercise and repeated sampling on
      cytology.
AB  - Bronchoalveolar lavage (BAL) was performed at weekly intervals in 10 Thoroughbred
      horses in race training (group 1) and in 4 rested horses (group 2) for 10 weeks.
      Lavages were continued on a weekly basis in 4 group 1 horses for an additional 9
      weeks (group 3). Cytological analysis of samples included leukocyte counts,
      erythrocyte counts, differential leukocyte counts, and haemosiderophage score.
      The mean leukocyte concentration was significantly lower in group 1 (92.1 +/- 4.6
      cells/microL) when compared with group 2 (133.5 +/- 8.2 cells/microL), P = 0.037.
      The differential leukocyte data were not significantly different between groups.
      There was a large amount of variability in the percentage of macrophages and
      lymphocytes in the differential counts over time with no obvious trends. The
      proportion of neutrophils demonstrated a tendency to decrease over time for both
      groups 1 and 2. Erythrocyte counts and haemosiderin scores were significantly
      higher in the exercising group than the rested horses. Neither exercise nor the
      technique itself evoked an inflammatory response in the BAL fluid.

PMID- 8534228
TI  - Outbreaks of proliferative haemorrhagic enteropathy on two pig farms.
AB  - Clinical signs of proliferative haemorrhagic enteropathy (PHE) including anaemia,
      dysentery and sudden death were observed in finisher pigs and young breeding
      stock on 2 farms. On farm A, PHE occurred 12 months after repopulation of the
      farm. Other outbreaks of PHE occurred after the withdrawal of therapeutic
      concentrations of in-feed antibacterial agents (farm A), or after monensin sodium
      (100 g/t) replaced olaquindox (100 g/t) in feed (farm B). The outbreaks, the
      possible sources of contamination and the role of antibacterial feed additives in
      the treatment and control of PHE are described.

PMID- 8534229
TI  - von Willebrand's disease in Dobermann dogs in Australia.
AB  - Over a 5-year period (1988-92), von Willebrand factor antigen (vWf:Ag)
      concentrations were determined on plasma samples from 614 Dobermanns. The vWf:Ag
      concentration was < 50 canine units (CU)/dL in 373 dogs (61%); these dogs were
      classified as carriers of the von Willebrand's disease (vWD) gene. In order to
      identify which dogs were at risk of haemorrhage due to vWD, we determined a cut
      off vWf:Ag concentration below which dogs could be considered at risk. This cut
      off was chosen in order to minimise the number of dogs genuinely at risk of
      haemorrhage, being wrongly classified as not at risk. This was done without
      sacrificing the specificity of the cut-off to any great extent. A vWf:Ag
      concentration of < 36 CU/dL was empirically chosen as the optimum cut-off
      concentration. In 282 dogs (76% of the carriers), the vWf:Ag concentration was
      below this cut-off and these dogs were, thus, classified as being at risk of
      haemorrhage due to vWD. Haemorrhage attributable to vWD was seen in 107 dogs (29%
      of the carriers, or 17% of all the dogs). Haemorrhage mostly followed trauma or
      surgery, but spontaneous genito-urinary and gastrointestinal haemorrhages were
      also frequent. Of these dogs, 92 were of known age, with a median of 3 years, and
      102 were of known sex, with 61% being female. In 89 dogs in which the severity of
      haemorrhage was subjectively assessed, mild and moderate bleeding occurred with
      similar frequency (48% and 43%, respectively). There were 8 cases of severe
      haemorrhage, with two deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534230
TI  - Blood supply of the ovine adrenal gland and its relevance in adrenal
      autotransplantation.
AB  - The arterial supply and venous drainage of 62 left and 5 right ovine adrenal
      glands is described, and the contribution of individual arteries to successful
      adrenal gland autotransplantation was evaluated. Arterial flow was measured by
      direct collection from the draining adrenal vein. Assessment of function of the
      transplanted adrenal gland was made from survival of the sheep and by the
      cortisol response to infusion of ACTH and the aldosterone secretory response to
      infusion of angiotensin II or potassium. For the left adrenal, the principal
      arterial supply was from the renal artery in 21 (34%), a lumbar artery in 32
      (52%), and the anterior mesenteric artery in 3. The total blood flow was 5.0 +/-
      SEM 0.4 mL/min, the flow from the renal branch 2.3 +/- 0.3 mL/min, and the
      principal lumbar branch 2.6 +/- 0.3 mL/min. Venous drainage from the left adrenal
      was via a major adrenal vein to the left renal vein, but additional tributaries
      to the renal vein were present in 26%. The arterial supply to the adrenal is
      regional and omission of a branch at transplantation could result in infarction
      of portion of the gland. By defining arterial supply and measuring blood flow,
      selection of the appropriate artery or multiple arteries can achieve an adrenal
      gland autotransplant survival of 90%.

PMID- 8534231
TI  - The spread of Corynebacterium pseudotuberculosis infection to unvaccinated and
      vaccinated sheep.
AB  - The decrease in the prevalence of Corynebacterium pseudotuberculosis after two
      generations of vaccination against the disease it causes, was used to estimate
      the rate of control of caseous lymphadenitis (CLA). Three groups of 150 sheep, of
      which 50 in each group were artificially infected with C pseudotuberculosis and
      100 in each group were uninfected sheep, were run separately for 40 months and
      shorn 5 times to promote the spread of CLA. One lot of 50 infected sheep and 2
      lots of 100 uninfected sheep were vaccinated against CLA. The rate of spread of
      CLA was recorded. Sheep vaccinated against CLA and naturally exposed to infection
      had a 74% lower infection rate than unvaccinated sheep. Sheep vaccinated against
      CLA and exposed to only vaccinated infected sheep had a 97% lower infection rate.
      Unvaccinated sheep had a 76% infection rate, with 77% of the transmission
      occurring at the 4th and 5th shearings, without any discharging CLA abscesses
      being observed. This study supports the view that in Australian wool producing
      flocks, CLA spreads mainly from sheep with discharging lung abscesses to sheep
      with shearing cuts. Vaccinated sheep infected with CLA have 96% fewer lung
      abscesses compared with unvaccinated infected sheep and are therefore less likely
      to spread this disease to other sheep.

PMID- 8534232
TI  - Trauma-induced blindness in two horses.

PMID- 8534233
TI  - Bovine papillomavirus type 4 in Australia.

PMID- 8534234
TI  - Poisoning of cattle attributed to Cucumis melo ssp agrestis (Ulcardo melon).

PMID- 8534235
TI  - Resistance of Fasciola hepatica to triclabendazole.

PMID- 8534236
TI  - Multiple cutaneous mast cell tumours in a cow.

PMID- 8534237
TI  - Relationship between vitamin B12 and cobalt concentrations in bovine liver.

PMID- 8534238
TI  - Equine morbillivirus pneumonia: susceptibility of laboratory animals to the
      virus.

PMID- 8534239
TI  - Ubiquity of myocardial stunning.
AB  - The prolonged depression of myocardial function following episodes of myocardial
      ischemia now known as myocardial stunning, appears ubiquitous in both the
      experimental and clinical settings. With recent therapies designed to ameliorate
      ischemic myocardium, e.g., coronary artery bypass, coronary thrombolysis,
      coronary angioplasty, the inexorable progression from ischemia to necrosis has
      been averted more successfully and frequently, which permits appearance of
      myocardial stunning to become clearer. Myocardial stunning occurs in the presence
      of a multitude of inciting stimuli to myocardial ischemia, including a fixed
      stenosis, relief from stenosis or even in the presence of reduced coronary
      reserve, without a coronary stenosis. It will be potentially most interesting to
      determine if myocardial stunning also belies the hibernating myocardium and is,
      in fact, its actual mechanism.

PMID- 8534240
TI  - Common methodological problems and artifacts associated with studies of
      myocardial stunning in vivo.

PMID- 8534241
TI  - Stunning: three questions and concerns.

PMID- 8534242
TI  - Do ATP-sensitive potassium channels play a role in myocardial stunning?

PMID- 8534243
TI  - Stunned myocardium: a disease of the myofilaments?

PMID- 8534245
TI  - Myocardial stunning: the role of oxidative substrate metabolism.

PMID- 8534244
TI  - Stunned myocardium, an opinionated review.
AB  - Brief coronary occlusions cause stunning and ischemic preconditioning, the
      molecular mechanisms of which are insufficiently known. A marked reprogramming of
      sarcolemmal functions (including those of the sarcoplasmic reticulum) seems to
      occur and may be the basis for many of the observed phenomena. A bewilderingly
      complex pattern of gene expression emerges from mRNA-studies with reperfused
      tissue which at present does not permit a focussed or coherent view of
      mechanisms.

PMID- 8534246
TI  - Adjustments in competitive substrate utilization in stunned myocardium during
      early reperfusion.

PMID- 8534247
TI  - Is stunned myocardium ischemic on a microvascular level?

PMID- 8534248
TI  - Absolute myocardial blood flow in chronic left ventricular dysfunction.

PMID- 8534249
TI  - Coronary vasomotion of the stunned myocardium.

PMID- 8534250
TI  - Therapy for myocardial stunning.

PMID- 8534251
TI  - Stunned myocardium: inotropic reserve and pharmacological attenuation.

PMID- 8534252
TI  - The elusive difference between hibernation and stunning in patients.

PMID- 8534253
TI  - Commentary on myocardial stunning and its clinical relevance.

PMID- 8534254
TI  - Chronic stunning: the new switch in thought.

PMID- 8534256
TI  - Hypothermic cardioplegia reduces the occurrence of spontaneous diastolic
      myofilament motion of the ischemic-reperfused rat heart.
AB  - Spontaneous diastolic myofilament motion of the isolated ischemic-reperfused rat
      heart was studied by the technique of laser spectroscopy. Scattered light
      intensity fluctuations (SLIF) from the exposed surface of the left ventricle of
      the quiescent perfused (Langendorff) rat heart were quantified by the
      autocorrelation function (R1F: frequency weighted by power), and by determining
      the average power of the SLIF signal (PS). The stabilized mean control (+/- SE)
      R1F (mV2/s2) and PS (mV2/s) values were: 0.87 +/- 0.07 and 21.3 +/- 1.5
      respectively. SLIF were characterized to index the extent of cell Ca(2+)-loading
      and the integrity of the sarcoplasmic reticulum (SR) functions by low Na+ and
      ryanodine perfusions. Low Na+ perfusion significantly increased the R1F values
      and produced pronounced spectral peaks between 0.5 and 2.5 Hz frequency bands;
      whereas ryanodine (1 microM) perfusion completely abolished the SLIF signals.
      Ischemia (34 degrees C, 60 min.) produced nearly a 12-fold increase in the R1F
      and PS values accompanied by a four-fold increase in the left ventricular end
      diastolic pressure (LVEDP) during the reperfusion period (34 degrees C, 30 min.)
      Pronounced reperfusion SLIF peaks were evident at the frequency bands between
      0.25-5.0 Hz. Hypothermic (10 degrees C) preservation during ischemia reduced the
      frequency and the amplitude of the SLIF signals at various frequencies and
      prevented the rise in LVEDP. As compared to hypothermia alone, hypothermic
      cardioplegia offered a slightly better preservation. But hypothermia alone or in
      combination with cardioplegia failed to completely normalize the post-ischemic
      R1F and PS values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534255
TI  - In situ mitochondrial function in volume overload- and pressure overload-induced
      cardiac hypertrophy in rats.
AB  - OBJECTIVES: Little comparative information is available on mitochondrial function
      changes during experimentally-induced hypertrophy. Respiratory control mechanisms
      are not exactly the same in situ and in isolated mitochondria. This study
      assessed in situ mitochondrial function in two myocardial hypertrophy models.
      METHODS: Cytochrome aa3 (Cytaa3) and myoglobin (Mb) absorption changes were
      monitored in isolated rat hearts using dual wavelength spectrophotometry (Cytaa3:
      605-630 nm, Mb: 581-592 nm). Hypertrophy was induced by creation of an aortic
      stenosis or of an aorto-caval fistula. Optical monitoring was performed on
      diastole-arrested perfused hearts using the sequence O2 perfusion, N2 perfusion
      during 4 min, and reoxygenation. The plateaus of the Cytaa3 and Mb curves were
      used to quantify oxidation-reduction and oxygenation levels. Respiratory kinetics
      were characterized by the slopes of transition phase curves. RESULTS: Myoglobin
      oxygenation was comparable in the hypertrophied and control hearts. However,
      Cytaa3 oxidation-reduction levels in the hypertrophied hearts showed a shift
      towards greater reduction in comparison with the controls (controls: 0.580 +/-
      0.008 DO605/DO630 nm, n = 34; fistula: 0.530 +/- 0.023, n = 23; stenosis: 0.522
      +/- 0.016, n = 20, p < 0.001). The rate of Cytaa3 reduction and the rate of
      myoglobin deoxygenation were significantly accelerated (p < 0.005) in the volume
      overload group (0.507 +/- 0.043, n = 23), whereas the respiratory rate in the
      pressure overload group (0.389 +/- 0.034, n = 20) was comparable to that in the
      control hearts (0.358 +/- 0.026 delta DO 605 nm/DO630 nm.min-1, n = 34).
      CONCLUSION: We found mitochondrial function alterations in both volume overload-
      and pressure overload-induced cardiac hypertrophy, despite adequate cytosol
      oxygenation. The patterns of these alterations differed: the redox state showed a
      shift of similar magnitude toward greater reduction in both models, but the
      respiratory rate was increased in the volume-overloaded hearts and unchanged in
      the pressure-overloaded hearts. The modification in the oxidation-reduction state
      suggested that overload hypertrophy may induce changes in the metabolism of the
      myocardium, which may, in turn, load to persistent modifications in mitochondrial
      function. The differences between the two models suggest that adaptation to
      hypertrophy-inducing events exists at the level of the mitochondrion.

PMID- 8534258
TI  - Calcitonin gene-related peptide activates the K+ channels of vascular smooth
      muscle cells via adenylate cyclase.
AB  - The aim of the present study was to examine the effects of calcitonin gene
      related peptide (CGRP) on the K+ channels of vascular smooth muscle cells.
      Cultured smooth muscle cells from a porcine coronary artery were studied using
      the patch-clamp technique. Extracellular application of 100 nM CGRP activated two
      types of K+ channels, the Ca(2+)-activated K+ channel (KCa channel) and the ATP
      sensitive K+ channel (KATP channel) in cell-attached patch configurations. In
      cells pretreated with Rp-cAMPS, a membrane-permeable inhibitor of cAMP-dependent
      protein kinase (PKA), extracellular application of 100 nM CGRP could not activate
      the KCa or KATP channel, indicating that the activation of the K+ channels by
      CGRP occurs in connection with PKA. In the cell-attached patch configurations,
      extracellular application of 1 mM dibutyryl cAMP, a membrane permeable cAMP,
      activated KCa and KATP channels. In inside-out patch configurations, application
      of PKA to the cytosolic side activated both the KCa and KATP channels. These
      results indicate that CGRP modulates the K+ channels of vascular smooth muscle
      cells via adenylate cyclase, i.e., cAMP-PKA pathway, and contributes to control
      of vascular tone.

PMID- 8534257
TI  - Quantification in crude homogenates of rat myocardial Na+, K(+)- and Ca(2+)
      ATPase by K+ and Ca(2+)-dependent pNPPase. Age-dependent changes.
AB  - Assays for complete quantification of Na+, K(+)- and Ca(2+)-ATPase in crude
      homogenates of rat ventricular myocardium by determination of K(+)- and Ca(2+)
      dependent p-nitrophenyl phosphatase (pNPPase) activities were evaluated and
      optimized. Using these assays the total K(+)- and Ca(2+)-dependent pNPPase
      activities in ventricular myocardium of 11-12 week-old rats were found to be 2.98
      +/- 0.10 and 0.29 +/- 0.02 mumol x min-1 x g-1 wet wt. (mean +/- SEM) (n = 5),
      respectively. Coefficient of variance of interindividual determinations was 7 and
      12%, respectively. The total Na+, K(+)- and Ca(2+)-ATPase concentrations were
      estimated to 2 and 10 nmol x g-1 wet wt., respectively. Evaluation of a putative
      developmental variation revealed a biphasic age-related change in the rat
      myocardial Ca(2+)-dependent pNPPase activity with an increase from birth to
      around the third week of life followed by a decrease. By contrast, the K(+)
      dependent pNPPase activity of the rat myocardium showed a decrease from birth to
      adulthood. It was excluded that the changes were simple outcome of variations in
      water and protein content of myocardium. Expressed per heart, the K(+)- and
      Ca(2+)-dependent pNPPase activity gradually increased to a plateau. The present
      assay for Na+, K(+)-ATPase quantification has the advantage over [3H] ouabain
      binding of being applicable on the ouabain-resistant rat myocardium, and is more
      simple and rapid than measurements of K(+)-dependent 3-O-methylfluorescein
      phosphatase (3-O-MFPase) in crude tissue homogenates. Furthermore, with few
      modifications the pNPPase assay allows quantification of Ca(2+)-ATPase on crude
      myocardial homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534259
TI  - Effects of PAF on cardiac function and eicosanoid release in the isolated
      perfused rat heart: comparison between normotensive and spontaneously
      hypertensive rats.
AB  - The aim of this study was (a) in isolated perfused rat heart to characterize the
      effects of platelet-activating factor (PAF) on coronary flow, ventricular
      contractility, and eicosanoid release and (b) to determine whether PAF effects
      are altered in hearts from spontaneously hypertensive rats (SHR). PAF (10(-10)
      10(-7) mol) dose-dependently decreased coronary flow and ventricular
      contractility; concomitantly, coronary effluent concentrations of thromboxane
      (TX)B2 and prostaglandin F2 alpha (PGF2 alpha) were elevated but not those of
      prostacyclin. The PAF receptor antagonist WEB 2086 (10(-7)-10(-5) mol/l)
      concentration-dependently antagonized these PAF effects. In addition; the cyclo
      oxygenase inhibitor indomethacin (5 x 10(-5) mol/l) prevented PAF (10(-9)-10(-7)
      mol) induced eicosanoid release; in the presence of indomethacin PAF caused
      coronary constriction and ventricular depression only at the highest dose (10(-7)
      mol) but had no effect at 10(-9) or 10(-8) mol. Moreover, the TXA2 antagonist
      SQ29,548 (10(-6) mol/l) completely inhibited 10(-8) mol PAF induced ventricular
      depression but did not effect coronary constriction. In SHR PAF (10(-9)-10(-7)
      mol) evoked decreases in coronary flow and ventricular contractility did not
      differ from those in normotensive Wistar-Kyoto rats while PAF induced TXA2 and
      PGF2 alpha release was markedly enhanced. In addition, decreases in coronary flow
      and ventricular contractility induced by the TXA2 agonist U 46619 (10(-7) mol/l)
      were markedly depressed in SHR. We conclude that in isolated perfused rat heart
      PAF causes coronary constriction and depression of ventricular function mainly
      indirectly through released TXA2 and/or PGF2 alpha. Moreover, the fact that in
      SHR the PAF effects on coronary flow and ventricular function are not altered
      despite markedly enhanced TXA2 and PGF2 alpha release supports the view that in
      the SHR the receptors mediating TXA2 and/or PGF2 alpha effects are desensitized.

PMID- 8534260
TI  - Transmural regulation of myocardial perfusion by neuropeptide Y.
AB  - In vivo studies have shown that sympathetic nerve stimulation improves the
      transmural distribution of myocardial perfusion by increasing the
      endocardial/epicardial flow ratio; however, the mechanism of this effect is
      unknown. During nerve stimulation both norepinephrine (NE) and neuropeptide Y
      (NPY) are released, either or both of which may exert vasoconstrictor effects.
      The present studies were performed to examine the effects of these two
      cotransmitters on the transmural distribution of myocardial perfusion in a canine
      model. In anesthetized open-chest dogs, during maximal coronary vasodilation with
      intracoronary adenosine, both neuropeptide Y (29.7 micrograms/min) and
      norepinephrine (0.5-2.0 micrograms/min) reduced myocardial perfusion to a greater
      extent in the epicardium than in the subendocardium. The endo/epi ratio with
      adenosine alone was 1.11 +/- 0.02. Norepinephrine increased this by 80%,
      neuropeptide Y by 20%, and the combination of the two by 76% (P < 0.05 for all
      three vs. adenosine). Neuropeptide Y alone constricted the coronary vasculature
      but did not alter transmural flow. Thus neuropeptide Y preferentially reduces
      myocardial perfusion in the epicardium. We speculate that neuronally released
      neuropeptide Y contributes importantly to the transmural distribution of
      myocardial perfusion during sympathetic nerve stimulation.

PMID- 8534261
TI  - The isoprostanes. Current knowledge and directions for future research.
AB  - The isoprostanes are a unique series of prostaglandin-like compounds formed in
      vivo from the free radical-catalyzed peroxidation of arachidonic acid independent
      of the cyclooxygenase enzyme. The purpose of this commentary is to summarize the
      status of our current knowledge regarding the isoprostanes and discuss what we
      consider to be avenues for further research. Novel aspects related to the
      biochemistry of isoprostane formation and methods by which these compounds are
      analyzed, including potential pitfalls that may occur during analysis, are
      discussed first. The isoprostanes possess potent biological activity, and their
      potential role in mediating certain aspects of the detrimental effects of oxidant
      stress is then examined. In addition, evidence is presented that these biological
      effects may be mediated through interaction with a unique receptor. A
      considerable portion of this commentary deals with the utility of measuring
      isoprostanes as markers of oxidant injury both in vitro and in vivo. A number of
      studies have shown these compounds to be extremely accurate markers of lipid
      peroxidation in animal models of oxidative stress and have illuminated the role
      of oxidant injury in association with several human diseases. Finally, based upon
      our current knowledge of the isoprostanes, directions for future research are
      proposed.

PMID- 8534262
TI  - A study of chimeras constructed with the two domains of angiotensin I-converting
      enzyme.
AB  - Angiotensin I-converting enzyme (ACE) is composed of two highly similar domains
      called the N and C domains, which display some contrasting enzymatic properties.
      We constructed two ACE chimeras: chimera 1, comprised of the N domain containing
      the central 60 amino acid residues of the C domain, and chimera 2, comprised of
      the C domain containing the central 60 amino acid residues of the N domain.
      Chimeras 1 and 2 displayed Km values for Hip-His-Leu and Z-Phe-His-Leu and kcat
      ratios for these two substrates similar to that of the N and C domains,
      respectively. Thus, the short sequence exchanged between the two domains does not
      confer the specific properties of that domain for these two substrates but,
      rather, such specific properties must arise from the sequences surrounding the
      central region in each domain.

PMID- 8534263
TI  - Inhibition of microsomal cytochromes P450 in rat liver by the tricyclic
      antidepressant drug desipramine and its primary oxidized metabolites.
AB  - N-Monoalkyl substituted tricyclic antidepressants like desipramine (DES) undergo
      cytochrome P450 (P450)-mediated biotransformation in liver to produce inhibitory
      metabolite-intermediate (MI) complexes with the enzyme. However, additional
      oxidation pathways that generate isolable metabolites have also been identified,
      so that the relationship between MI complexation and total oxidative metabolism
      is unclear. The present study investigated the capacity of DES and three putative
      metabolites (2-hydroxy- and 10-hydroxy-DES and N,N-didesmethylimipramine; DIDES)
      to elicit MI complexation and inhibit P450-dependent activities in rat liver. MI
      complexation of P450 was produced by DES, but not with the three metabolites, in
      NADPH-supplemented microsomes. Consistent with this finding, inhibition of
      testosterone hydroxylation pathways was enhanced markedly by prior incubation of
      DES with NADPH and microsomes. Direct addition of DIDES to incubations resulted
      in significant inhibition of P450 activities (IC50s of 35 and 29 microM against
      estradiol 6 beta- and 16 alpha-hydroxylation mediated by P450s 3A2 and 2C11,
      respectively). Neither 2-hydroxy- nor 10-hydroxy-DES directly inhibited
      testosterone hydroxylation (IC50s > 100 microM). However, after a preincubation
      step between these metabolites and NADPH-fortified microsomes, enhanced
      inhibition of reactions mediated by P450 3A2 and P450 2C11/2A1 was produced by 2
      hydroxy-DES and 10-hydroxy-DES, respectively. Metabolism of DES to DIDES and 2
      hydroxy-DES was estimated as 7.77 +/- 0.48 nmol/mg protein/hr (10-hydroxy-DES was
      not detected). It is likely that secondary oxidized metabolites derived from 2
      hydroxy-DES, as well as the primary metabolite DIDES, may contribute to the
      inhibition of P450 activity during DES biotransformation. These results indicate
      that the 2-hydroxy-, 10-hydroxy-, and N-desmethyl-metabolites of DES are not
      involved in MI complexation, but complexation is not the sole mechanism by which
      DES inhibits microsomal drug oxidation that may lead to pharmacokinetic drug
      interactions.

PMID- 8534264
TI  - Meloxicam: influence on arachidonic acid metabolism. Part 1. In vitro findings.
AB  - Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from
      enolic acid. Meloxicam has shown potent anti-inflammatory activity in animal
      models together with low gastrointestinal and renal toxicity. Studies were
      undertaken to compare meloxicam to other NSAIDS in their ability to inhibit
      either constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2).
      COX-1 was isolated as a cell-free enzyme from bovine seminal vesicles or bovine
      brain or was present in nonstimulated macrophages derived from the guinea-pig
      peritoneum. COX-2 was induced in peritoneal macrophages stimulated by
      lipopolysaccharide (LPS) or isolated as a cell-free enzyme from sheep placenta.
      Of all NSAIDs tested, meloxicam was the most selective inhibitor of COX-2 in
      intact cells. In cell-free enzyme preparations, however, meloxicam showed the
      same activity against COX-1 and COX-2. All other NSAIDs tested were more potent
      inhibitors of COX-1 than of COX-2. The inducible cyclooxygenase COX-2 has been
      implicated in the mediation of the inflammatory reaction, whereas the products of
      the constitutive cyclooxygenase COX-1 have cytoprotective effects in the gastric
      mucosa, support microcirculation in the kidney, and are antithrombogenic.
      Therefore, differential inhibitory effects of NSAIDs on COX-1 and COX-2 may have
      a bearing on the risk-benefit profile displayed in clinical practice. Meloxicam
      shows a preferential inhibitory effect on COX-2 over COX-1, which may be directly
      related to the favorable tolerability profile with potent anti-inflammatory
      effects observed in animal studies.

PMID- 8534265
TI  - Meloxicam: influence on arachidonic acid metabolism. Part II. In vivo findings.
AB  - Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from
      enolic acid. Preclinical studies have indicated that meloxicam has potent anti
      inflammatory activity, together with a good gastrointestinal and renal
      tolerability profile. This report summarizes studies undertaken to compare
      meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX
      2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their
      influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach,
      kidney, brain, and blood. In pleurisy of the rat, meloxicam was twice as potent
      as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac,
      and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2)
      biosynthesis. In the peritonitis model in mice, meloxicam was approximately twice
      as active as piroxicam, and more than 10 times as active as diclofenac in the
      suppression of PGE biosynthesis. Doses of meloxicam sufficient to inhibit PGE2
      biosynthesis in the pleural exudate and peritoneal exudate had no influence on
      leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of meloxicam
      on the PGE2 content of rat gastric juice and rat urine was weaker than that of
      piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2
      concentration in brain of rats and mice (induced by convulsant doses of
      pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker
      effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or
      tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted
      separately, showing that meloxicam preferentially inhibits COX-2 over COX-1. COX
      2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX
      1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential
      selectivity for one isoenzyme over another, as displayed by meloxicam, may have
      implications in the clinical setting in terms of a more favorable risk: benefit
      profile.

PMID- 8534266
TI  - Effects of curcumin on cytochrome P450 and glutathione S-transferase activities
      in rat liver.
AB  - The stability of curcumin, as well as the interactions between curcumin and
      cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were
      studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The
      stability of curcumin was strongly improved by lowering the pH or by adding
      glutathione (GSH), N-acetyl L-cysteine (NAC), ascorbic acid, rat liver
      microsomes, or rat liver cytosol. Curcumin was found to be a potent inhibitor of
      rat liver P450 1A1/1A2 measured as ethoxyresorufin deethylation (EROD) activity
      in beta-naphthoflavone (beta NF)-induced microsomes, a less potent inhibitor of
      P450 2B1/2B2, measured as pentoxyresorufin depentylation (PROD) activity in
      phenobarbital (PB)-induced microsomes and a weak inhibitor of P450 2E1, measured
      as p-nitrophenol (PNP) hydroxylation activity in pyrazole-induced microsomes. Ki
      values were 0.14 and 76.02 microM for the EROD- and PROD-activities,
      respectively, and 30 microM of curcumin inhibited only 9% of PNP-hydroxylation
      activity. In ethoxyresorufin deethylation (EROD) and pentoxyresorufin
      depentylation (PROD) experiments, curcumin showed a competitive type of
      inhibition. Curcumin was also a potent inhibitor of glutathione S-transferase
      (GST) activity in cytosol from liver of rats treated with phenobarbital (PB),
      beta-naphthoflavone (beta NF) and pyrazole (Pyr), when measured towards 1-chloro
      2,4-dinitrobenzene (CDNB) as substrate. In liver cytosol from rats treated with
      phenobarbital (PB), curcumin inhibited GST activity in a mixed-type manner with a
      Ki of 5.75 microM and Ki of 12.5 microM. In liver cytosol from rats treated with
      pyrazole (Pyr) or beta-naphthoflavone (beta NF), curcumin demonstrated a
      competitive type of inhibition with Ki values of 1.79 microM and 2.29 microM,
      respectively. It is concluded that these strong inhibitory properties of curcumin
      towards P450s and GSTs, in addition to its well-known antioxidant activity, may
      help explain the previously observed anticarcinogenic, antimutagenic, and
      cytoprotective effects of this important natural compound and food constituent.

PMID- 8534267
TI  - Effect of curcumin on certain lysosomal hydrolases in isoproterenol-induced
      myocardial infarction in rats.
AB  - The effect of curcumin on lysosomal hydrolases in serum and heart was studied by
      determining the activities of beta-glucuronidase, beta-N-acetylglucosaminidase,
      cathepsin B, cathepsin D, and acid phosphatase. Rats treated with isoproterenol
      (30 mg/100 g body weight) showed a significant increase in serum lysosomal
      hydrolase activities, which were found to decrease after curcumin treatment.
      Isoproterenol administration to rats resulted in decreased stability of the
      membranes, which was reflected by the lowered activity of cathepsin D in
      mitochondrial, lysosomal, and microsomal fractions. Curcumin treatment returned
      the activity levels almost to normal, showing that curcumin restored the normal
      function of the membrane. Histopathological studies of the infarcted rat heart
      also showed a decreased degree of necrosis after curcumin treatment.

PMID- 8534268
TI  - Antitumor 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone derivatives. Interactions with
      tubulin.
AB  - A series of derivatives of 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone (DHQZ) with
      known antitumor activity was re-evaluated in the National Cancer Institute cancer
      cell line screen. Analysis by the COMPARE algorithm suggested that their
      cytotoxicity derived from interactions with tubulin. Significant inhibition of
      tubulin assembly and of the binding of radiolabeled colchicine to tubulin was
      demonstrated with several of the compounds, particularly NSC 145669, 175635, and
      175636. The DHQZ derivatives are structurally analogous to a number of
      antimitotic agents, flavonols and derivatives of 2-styrylquinazolin-4(3H)-one and
      of 2-phenyl-4-quinolone. Structure-activity analogies between these agents, the
      combretastatins, and the colchicinoids were analyzed and summarized.

PMID- 8534270
TI  - Radiolabelling of the human 5-HT2A receptor with an agonist, a partial agonist
      and an antagonist: effects on apparent agonist affinities.
AB  - Previous work has shown that 5-hydroxytryptamine (5-HT)2A receptors can be
      radiolabelled with various radioligands, including partial agonists, such as
      [125I]-DOI and [3H]-DOB, and antagonists, such as [3H]-ketanserin and [3H]
      spiperone. Because 5-HT has high affinity for the 5-HT2A receptor when displacing
      [3H]-DOB, the purpose of the present study was to determine whether or not the
      receptor could be labelled with [3H]-5-HT and what would be the effect of
      labelling the receptor with various radioligands having differing efficacies at
      the receptor. Consequently, the human 5-HT2A receptor stably expressed in NIH 3T3
      cells was radiolabelled with the endogenous agonist [3H]-5-HT, the partial
      agonist [3H]-DOB, and the antagonist [3H]-ketanserin. The receptor could be
      radiolabelled with [3H]-5-HT with a Kd value of 1.3 +/- 0.1 nM and a Bmax value
      of 3461 +/- 186 fmoles/mg protein and the radiolabelling was sensitive to the
      stable guanosine 5'-triphosphate (GTP) analogue guanylyl-imidodiphosphate (GMP
      PNP). Ketanserin labeled significantly more receptors (Kd = 1.1 +/- 0.1 nM: Bmax
      = 27,684 +/- 1500 fmoles/mg protein) than [3H]-DOB (Kd = 0.8 +/- 0.08 nM: Bmax =
      8332 +/- 16 fmoles/mg protein) which, in turn, labelled significantly more
      receptors than [3H]-5-HT. The apparent affinity of antagonists did not change
      when the receptor was radiolabelled with either [3H]-agonists or [3H]
      antagonists; however, agonists had a higher apparent affinity for [3H]-agonist
      labeled receptors than for [3H]-antagonist-labeled receptors. Therefore, the
      apparent affinity of agonists for the 5-HT2A receptor estimated from displacement
      experiments depends on the intrinsic efficacy of the radioligand used.

PMID- 8534269
TI  - Effects of diet and ethanol on the expression and localization of cytochromes
      P450 2E1 and P450 2C7 in the colon of male rats.
AB  - Local activation of procarcinogens in target tissues such as the colon by
      cytochrome P450-dependent microsomal monooxygenases is considered to be an
      important factor in the etiology of cancer. Diet and alcohol consumption are
      considered risk factors in colon cancer, and the cytochrome P450 isozymes CYP2E1
      and CYP2C7 have been implicated in the biochemical mechanisms underlying colon
      cancer. The current study was conducted to determine the effects of diet and
      ethanol consumption on colonic and hepatic expression of these two enzymes. Adult
      male rat Sprague-Dawley rats were fed rat chow ad lib. or were infused
      intragastrically with control or ethanol-containing diets. Our results indicate
      that CYP2E1 is present in colonic epithelial cells, and expression of colonic and
      hepatic microsomal CYP2E1 and CYP2C7 was increased by chronic ethanol intake. As
      compared with rats having ad lib. access to standard rat food, rats receiving
      total enteral nutrition had significant (P < 0.01) reductions of CYP2C7 and
      slight, but not statistically significant, reductions in the expression of CYP2E1
      in colon. Diet and ethanol differentially regulated CYP2E1 and CYP2C7 in a tissue
      specific manner such that the ethanol induced CYP2E1 and CYP2C7 in the colon and
      liver, and the intragastric diet alone had a tendency to induce these isozymes in
      the liver and reduce them in the colon. These results may provide a partial
      explanation for the mechanism underlying effects of diet and ethanol on colon
      cancer.

PMID- 8534271
TI  - Modulation of serotonin binding sites in Spisula solidissima oocytes by phorbol
      ester.
AB  - In Spisula solidissima oocytes, serotonin (5-hydroxytryptamine, 5-HT)-dependent
      meiosis reinitiation is mediated via specific 5-HT membrane binding sites. This
      oocyte response is inhibited by the phorbol ester TPA. To assess whether the
      inhibitory effect of TPA was due to alteration of oocyte membrane binding sites,
      we studied their characteristics after TPA treatment. [3H]-5HT binding assays
      revealed that TPA decreased the affinity and, after prolonged treatment,
      increased the number of oocyte binding sites. Moreover, inhibitory actions of TPA
      on 5-HT-induced meiosis reinitiation paralleled its inhibitory effects on 5-HT
      binding site affinity. The inhibitory actions in biological assays were
      restricted to TPA (an inactive analog of TPA, TPA-met was inefficient) and were
      completely reversed by staurosporine. Our data thus suggest an inhibitory role
      for protein kinase C on oocyte 5-HT binding sites under physiological conditions.

PMID- 8534272
TI  - Effects of calcium antagonists nifedipine and flunarizine on phencyclidine
      induced changes in the regional dopaminergic metabolism of the rat brain.
AB  - To elucidate the psychotropic actions of calcium (Ca) antagonists, we
      investigated the effect of the voltage-dependent Ca channel antagonists,
      nifedipine and flunarizine, on phencyclidine (PCP)-induced changes in the
      monoamine metabolism in the regional brain areas of rats. The results indicate
      that the administration of nifedipine alone attenuated dopamine (DA) metabolism
      in the nucleus caudatus putamen while enhancing serotonin (5-HT) metabolism. By
      contrast, flunarizine increased DA metabolism. PCP significantly increased DA
      metabolite levels in the prefrontal cortex, the nucleus caudatus putamen, and the
      amygdala. The PCP-induced increases in DA metabolism in these regions were
      significantly antagonized by nifedipine, but not by flunarizine. These results
      indicate that nifedipine attenuates the PCP-induced hyperactivity of the
      dopaminergic neurons, suggesting antipsychotic properties for this drug.

PMID- 8534273
TI  - Glutathione and glutathione S-transferase in benign and malignant prostate cell
      lines and prostate tissues.
AB  - Metastatic prostate adenocarcinoma is unresponsive to alkylator chemotherapy with
      virtually no prolonged remissions. Glutathione (GSH) and glutathione S
      transferase (GST) have been reported to play a role in tumor resistance to
      alkylator therapy; however, there are no baseline studies that have investigated
      and compared GSH and GST in human prostate cell lines and tissues. Thus, we
      determined the GSH content and GST activity in benign prostate, in primary and
      metastatic prostate adenocarcinoma tissues, in immortal adenocarcinoma cell
      lines, and in primary cell cultures derived from both benign prostate and primary
      prostatic carcinoma tissue. The GSH content was higher in the immortal cell lines
      than in the fresh tissues and primary cultures. Conversely, the GST activity was
      significantly higher in the tissues and primary cultures than in the cell lines.
      The GSH content and GST activity of the primary cultured prostatic cells were
      similar to those of the prostate tissues. The differences between the immortal
      prostate cancer cell lines and prostate tissue are of sufficient magnitude to
      suggest that in vitro results with cell lines may not extrapolate to prostate
      cancer in vivo. The GSH content and GST activity in a prostate specific antigen
      secreting human prostate tumor xenograft, LuCaP23, maintained in nude mice were
      similar to those of human prostate tissue and primary cultures. Both the
      xenograft and primary cultures from patients with prostate cancer may be more
      appropriate models than established cell lines for investigating techniques to
      increase the effectiveness of alkylators in prostate cancer.

PMID- 8534274
TI  - Cerebrospinal fluid corticotropin and cortisol are reduced in infantile spasms.
AB  - Infantile spasms respond to ACTH, and levels of the hormone in cerebrospinal
      fluid of untreated infants with this disorder were found to be lower than in age
      matched controls. In this study we analyzed cerebrospinal fluid cortisol and ACTH
      using improved immunoassays in a larger cohort of infants with infantile spasms.
      Analysis of 20 patients and 15 age-matched controls revealed significantly lower
      levels of both ACTH and cortisol in the cerebrospinal fluid. These data, combined
      with the efficacy of ACTH and glucocorticoids for infantile spasms, support an
      involvement of the brain-adrenal-axis in this disorder.

PMID- 8534275
TI  - Neurologic and other disorders in relatives of pediatric patients with CNS
      tumors.
AB  - Abnormalities of embryogenesis and nervous system development may cause or
      contribute to the development of childhood brain tumors. To identify genetic or
      environmental factors that may be associated with etiologies of childhood central
      nervous system tumors, we examined family histories of 165 children with such
      tumors for the presence of neurologic disorders, including neural tube defects,
      mental retardation, seizures, and central nervous system tumors, as well as other
      cancers and birth defects. Only 1 patient, with the neurofibromatosis-Noonan
      syndrome, was confirmed to have an underlying syndromic diagnosis associated with
      central nervous system tumorigenesis. Families of 2 probands with posterior fossa
      primitive neuroectodermal tumors reported relatives with olivopontocerebellar
      atrophy. Although increased incidences of study disorders were not identified in
      this population, it is possible that within individual families one or more of
      these disorders is related to childhood central nervous system tumorigenesis.

PMID- 8534276
TI  - Clinical and developmental findings in children with giant interhemispheric cysts
      and dysgenesis of the corpus callosum.
AB  - Giant interhemispheric cysts in association with dysgenesis of the corpus
      callosum are rare. Clinical and developmental data concerning affected patients
      are limited, the pathologic basis for these cysts has not been established, and
      prognosis is uncertain. The purpose of our study was to describe the clinical and
      developmental findings for 11 children with giant interhemispheric cysts,
      dysgenesis of the corpus callosum, and ventricular dilatation. Eight of the
      children required ventriculoperitoneal shunting, eight had normal neurologic
      examinations, and seven had experienced seizures. Seizure control appeared to
      correlate with neurodevelopmental function. Cognitively, children ranged from the
      average to mildly/moderately retarded level. Language delays were frequent,
      particularly in children with predominantly left hemispheric cysts. Adaptive
      behavior was mildly delayed with weakness observed in motor skills. Despite the
      striking neuroimaging abnormalities, our findings suggest the possibility of only
      mildly delayed neurodevelopmental outcome is good for children with this
      constellation of neurologic anomalies.

PMID- 8534277
TI  - Effects of ACTH on brain midline structures in infants with infantile spasms.
AB  - Changes of the midline structures of the brain, including the pons, cerebellar
      vermis, and corpus callosum, induced by adrenocorticotropic hormone (ACTH)
      therapy in 7 infants with infantile spasms were investigated using magnetic
      resonance imaging. Decreased volume of these parts of the brain was induced in
      almost all infants. Decreased volume of the pons was thought to be closely
      related to sleep disturbance during ACTH therapy. These results may demonstrate
      that the cessation of convulsive episodes in infants with infantile spasms
      treated with ACTH is due to its direct action on the brainstem.

PMID- 8534278
TI  - Complex partial status epilepticus in childhood.
AB  - We report 5 pediatric patients (2 male, 3 female; age range: 4-8 years) with
      complex partial status epilepticus (CPSE). Four patients had previous illnesses
      and mild motor or mental retardation. In 2 patients, CPSE was induced by
      inappropriate management or selection of antiepileptic drugs. Clinical features
      varied and automatisms were observed in 3 patients. In 1 patient, decreased
      physical tone with syncope and impaired consciousness with amaurosis were
      observed. The episodes of CPSE were continuous in 3 patients and recurrent in 2
      patients. In 4 patients, ictal electroencephalographic (EEG) findings, including
      video-EEG analyses of 3 patients, demonstrated persistent focal epileptic
      features. Intravenous diazepam abolished CPSE in 3 patients with brief periods of
      definite EEG localizations remaining. In 4 patients, seizure prognoses were
      favorable after appropriate treatments; in 1 patient, seizures were intractable
      even after antiepileptic drug administration.

PMID- 8534279
TI  - Flunarizine of limited value in children with intractable epilepsy.
AB  - Fourteen ambulatory children and adolescents with intractable epilepsy were
      studied in an open phase II study to investigate the pharmacokinetics and
      pharmacodynamics of flunarizine as an add-on treatment. Flunarizine was given in
      increasing doses starting with 0.1-0.3 mg/kg/day until effect was observed or a
      steady-state plasma concentration of 50-60 ng/ml was reached. Treatment was
      continued for 3 months at steady state. Pharmacokinetics were determined during
      the immediate posttreatment period. Positive antiepileptic effect (> or = 50%
      reduction in seizure frequency) was observed in 4 of 14 patients (29%; 95% CI: 52
      5). Independently of antiepileptic effect, 10 of 14 parents (71.4%; 95% CI: 95
      48) observed positive cognitive effects. In all patients treatment was withdrawn
      due to either lack of effect or weight gain. Flunarizine was rapidly absorbed;
      mean time of peak concentration (Tmax) was 2.7 hours (range: 1-8). The mean
      terminal half-life was 23.2 days (range: 7-48), the total plasma clearance of
      flunarizine per fraction of the dose absorbed (CLp/F) was 0.28 ml/min/kg (range:
      0.07-042), and the volume of distribution of flunarizine per fraction of the dose
      absorbed (Vd/F) was 187 L/kg (range: 99-348). We conclude that flunarizine (0.1
      0.3 mg/kg/day) seems to be of limited antiepileptic value in children with
      intractable epilepsy. The pharmacokinetic profile of flunarizine complicates its
      clinical use.

PMID- 8534280
TI  - Prospective follow-up of primitive reflex profiles in high-risk infants: clues to
      an early diagnosis of cerebral palsy.
AB  - To clarify reflex profiles in the first year of life in connection with
      categories of neurologic abnormality, eight primitive reflexes (i.e., the palmar
      grasp reflex, the plantar grasp reflex, the Galant response, the asymmetric tonic
      neck reflex, the suprapubic extensor reflex, the crossed extensor reflex, the
      Rossolimo reflex, and the heel reflex) were prospectively examined in 204 high
      risk infants, of whom 58 developed cerebral palsy, 22 had developmental
      retardation, and 124 were normal at follow-up examination at 2 years of age. The
      change in the retention time of reflex activity for each of these reflexes was
      characteristic for each category or type of neurologic abnormality: retention of
      palmar grasp reflex, suprapubic extensor reflex, crossed extensor reflex,
      Rossolimo reflex, and heel reflex in spastic cerebral palsy, as well as retention
      of plantar grasp reflex, Galant reflex, and asymmetric tonic neck reflex in
      athetoid cerebral palsy and somewhat weaker retention of these reflexes in
      developmental retardation (statistical significance P < .001 compared with
      normally developed patients). These characteristic changes imply that a
      presumptive diagnosis can be made in neurologically high-risk infants by
      examination of the primitive reflexes, which are of specific significance among
      the other neurologic criteria within the first year of life.

PMID- 8534281
TI  - Trihexyphenidyl and isoprinosine in the treatment of subacute sclerosing
      panencephalitis.
AB  - Six cases of subacute sclerosing panencephalitis (1 stage I, 3 stage II, 2 stage
      III) were diagnosed at our institution in the last 10 years. Five patients were
      treated with isoprinosine and the antiepileptic drug valproic acid. Three
      patients presented with myoclonic seizures refractory to valproic acid and the
      usual antiepileptic therapy. They received trihexyphenidyl with good results. We
      suggest the use of trihexyphenidyl in combination with isoprinosine in patients
      with subacute sclerosing panencephalitis with myoclonic seizures refractory to
      valproic acid.

PMID- 8534282
TI  - A lectin and synaptophysin study of developing brain.
AB  - Lectins which bind to carbohydrate residues of glycoconjugates can be used as
      histochemical markers of these substances. A battery of lectins including peanut
      agglutinin, ricinus communis, wheat germ agglutinin, soybean agglutinin,
      concanavalin ensiformis, Ulex europaeus, and Dolichos biflorus as well as
      synaptophysin was used on paraffin-embedded human fetal and infant brains of
      varying gestation (20 weeks to term) to determine whether there were changes in
      the pattern of glycoconjugate staining. The findings indicate that lectin binding
      of several of these markers changes with gestation as does synaptophysin.

PMID- 8534283
TI  - Expression of beta-amyloid precursor protein in axons of periventricular
      leukomalacia brains.
AB  - Human beta-amyloid precursor protein immunoreactivity was demonstrated in axonal
      swellings (spheroids) around periventricular leukomalacia (PVL) of neonates.
      Immunoreactive axons were found at the early, but not late stage of PVL. beta
      Amyloid precursor protein immunoreactivity was homogeneous in damaged axons at
      the early stage of PVL manifesting microglial activation, concentrated at the
      center of axonal swellings at the subsequent stage manifesting astrogliosis, and
      undetectable at the terminal stage of cavitation or neovasculation.
      Immunostaining for beta-amyloid precursor protein was useful in localizing PVL
      lesions at their early stages.

PMID- 8534284
TI  - Pentobarbital therapy for status epilepticus in children: timing of tapering.
AB  - Three children with refractory status epilepticus, unresponsive to intravenous
      administration of diazepam, phenytoin, and lidocaine, received pentobarbital
      therapy and were monitored by electroencephalography (EEG). They required
      mechanical ventilation and vasopressor therapy. Intravenous pentobarbital therapy
      was successful and without distinct sequelae in all 3 patients, and could be
      incrementally discontinued without breakthrough seizures after 12-65 hours of a
      burst-suppression or complete suppression pattern on EEG. Obtaining a suppression
      pattern was important for controlling status epilepticus in children as well as
      adults. We suggest that 12 hours after a burst-suppression pattern is obtained,
      tapering of pentobarbital should be attempted to avoid serious complications of
      extended pentobarbital anesthesia (e.g., respiratory depression, hypotension,
      pneumonia).

PMID- 8534285
TI  - Ito hypomelanosis and moyamoya disease.
AB  - A transient ischemic attack with nearly complete progressive recovery occurred at
      age 20 months in a girl with Ito's hypomelanosis. Outcome included mental
      deficiency and behavioral difficulties requiring special education, but without
      recurrence of ischemic attack. The angiographic investigation performed at 9
      years of age disclosed bilateral stenosis of the internal carotid artery
      characteristic of moyamoya disease. This association has not been reported
      previously.

PMID- 8534286
TI  - Tuberous sclerosis associated with histologically confirmed ocular and cerebral
      tumors.
AB  - The clinical, neuroradiologic, and pathologic features of an unusual retinal and
      cerebral giant cell astrocytoma in a 24-year-old man with tuberous sclerosis are
      reported. The patient was referred at 3 years of age because of partial seizures
      from the first months of life, severe mental retardation, and left
      microphthalmos. The microphthalmic eye presented slow growth from 9 years of age
      and was enucleated at age 18 years because of exophthalmos and pain. At age 23
      years, the patient experienced sudden and severe headache. Magnetic resonance
      imaging revealed a voluminous cystic tumor in the region of the foramen of Monro,
      lateral ventricle, and basal ganglia of the right cerebral hemisphere. Pathologic
      examination of the enucleated eye and of the cerebral tumor disclosed the same
      histologic findings in both locations, a giant cell astrocytoma.

PMID- 8534287
TI  - Alobar holoprosencephaly with diabetes insipidus and neuronal migration disorder.
AB  - A 2-year-old girl with alobar holoprosencephaly associated with facial
      abnormalities, central diabetes insipidus, and a neuronal migration disorder is
      reported. The diagnosis of diabetes insipidus was based on low urine osmolality
      and low plasma ADH concentration during a water deprivation test, and clinical
      and biochemical improvement after desmopressin acetate administration. Because
      the posterior portion of the pituitary was located in the sella turcica and the
      hypothalamo-pituitary stalk was intact, the diabetes insipidus was presumed to
      have been caused by hypothalamic osmoreceptor dysfunction. MRI findings were
      compatible with alobar holoprosencephaly. In addition, heterotopic gray matter
      was recognized as a continuous band over a single ventricle. Defective cleavage
      of the prosencephalon associated with a neuronal migration disorder is
      characteristic of alobar holoprosencephaly.

PMID- 8534288
TI  - Ectopic or heterotopic? An appeal for semantic precision in describing
      developmental disorders of the nervous system.

PMID- 8534289
TI  - HSAN IV and neurotrophins.

PMID- 8534290
TI  - Congenital muscular dystrophies: clinical review and proposed classification.
AB  - The clinical spectrum of the congenital muscular dystrophies is reviewed using as
      a sample population 10 Sicilian patients with various clinical subtypes. A
      comprehensive classification scheme for the muscular dystrophies is presented
      based on recent advances in our understanding of this heterogeneous group of
      syndromes.

PMID- 8534291
TI  - Anterior-inferior (5 o'clock) portal for shoulder arthroscopy.
AB  - The present study describes an anterior-inferior portal for arthroscopic shoulder
      instrumentation at the 5 o'clock position along the glenoid rim. An anterior
      inferior portal was established in 14 cadaver shoulders. The portal was created
      in an inside-to-outside fashion, with the humerus maximally adducted, directing
      the guide rod as far lateral as possible. Using the described technique, a 5
      o'clock portal travels through the subscapularis and lateral to the conjoined
      tendon. Distance between the portal and the musculocutaneous nerve was 22.9 +/-
      4.9 mm (mean +/- SD), and 24.4 +/- 5.7 mm between the portal and the axillary
      nerve. Previously described portals were either at, or above the 3 o'clock
      position, resulting in an acute, difficult angle of approach to the glenoid neck.
      Through a combination of proper arm positioning and rod insertion technique, the
      5 o'clock portal can be created safely and is of great potential utility for
      arthroscopic shoulder stabilization procedures.

PMID- 8534292
TI  - Posterior cruciate ligament injuries in trauma patients: Part II.
AB  - The purpose of this article is to present the incidence of posterior cruciate
      ligament (PCL) injuries in trauma patients with acute hemarthrosis of the knee.
      There were 222 acute knee injuries with hemarthrosis presented to our regional
      trauma center over a 38-month period. PCL injuries occurred in 38% (85 of 222)
      acute knee injuries; 56.5% (48 of 85) were trauma patients, and 32.9% (28 of 85)
      were sports related. Higher energy mechanisms may account for the difference.
      Isolated PCL injuries were rare (3.5%, 3 of 85), whereas 96.5% (82 of 85) of PCL
      injuries occurred in combination with other ligament injuries. Trauma patients
      have a higher incidence of PCL injuries than do athletes. Acute knee hemarthrosis
      in trauma patients should elevate suspicion for multiple knee ligament injuries
      involving the posterior cruciate ligament.

PMID- 8534293
TI  - Posterior superior glenoid impingement: expanded spectrum.
AB  - Posterior superior glenoid impingement is a recently recognized mechanism of
      injury producing rotator cuff injury in athletes. Usually the mechanism is
      repetitive overhand activity such as throwing. A survey of the author's practice
      was undertaken to show a wider spectrum of this mechanism both in the activity
      that caused it and the number of structures at risk of injury from this
      mechanism. The survey revealed 11 patients who had a clear recollection of their
      mechanism of injury and an objective documentation of the injury by arthroscopy
      or imaging studies. The majority of shoulders had damage to more than one of the
      five structures at risk from this mechanism of injury. Six cases were not sports
      related. Glenoid impingement may injure one or more of the following: (1)
      superior labrum, (2) rotator cuff tendon, (3) greater tuberosity, (4) inferior
      glenohumeral ligament or labrum, and (5) superior glenoid bone. Injury to more
      than one structure may be the rule and injury to one structure may indicate
      investigation of the other four.

PMID- 8534294
TI  - Preliminary results of an absorbable interference screw.
AB  - A randomized, prospective multicenter comparison was done of a bioabsorbable
      interference screw (Bioscrew; Linvatec Corp, Largo, FL) made from poly L-lactic
      acid and a metal interference screw produced by the same company. Assignment was
      randomized by sealed envelopes. A total of 110 patients underwent arthroscopic
      patellar tendon autografts. A minimum 12 months follow-up is available on 85
      patients (mean 19 months, range 12 to 33) including 42 with Bioscrews and 43 with
      metal screws. There were 56 male and 29 female patients. The average age was 29
      years (16 to 50 years). Tourniquet times and associated surgical findings were
      similar for the two groups. Postoperative Tegner and Lysholm scores were not
      statistically different between the two groups. KT tests at 1 year showed an
      average 20-lb laxity of 1.8 mm for the Bioscrew and 1.2 mm for the metal screw
      groups. The average 1-year KT maximum manual side-to-side difference was 1.6 mm
      for Bioscrews and 1.6 mm for metal screws. A pivot shift was absent in 83% of
      Bioscrews and 90% of metal screws at follow-up. Six of 85 Bioscrews inserted (7%)
      broke on insertion (all were 7-mm diameter screws at the femoral site). No
      additional fixation was required in four cases. In two, the broken screw was
      replaced. No lytic bone changes or tunnel widening were found with any Bioscrew.
      One metal screw had tibial tunnel widening. No statistical difference was found
      between the Bioscrew and the metal screw groups. Short-term data support the
      conclusion that the Bioscrew is a reasonable alternative to metal interference
      screws.

PMID- 8534295
TI  - Arthroscopic subacromial decompression with and without the Holmium:YAG-laser. A
      prospective comparative study.
AB  - The purpose of this study was to critically evaluate the results of laser
      assisted arthroscopic subacromial decompression (ASD) and compare them with the
      results of a conventional arthroscopic procedure. In a prospective study, 52
      patients with stage II and III (partial tear) impingement syndrome undergoing ASD
      were divided into two consecutive groups. The first 18 patients underwent
      conventional arthroscopic surgery using shaver and electrocautery (group S). The
      following 34 patients underwent ASD with the Holmium:YAG-laser (22 watt) and
      without electrocautery (group L). Subjective, objective, and functional results
      were assessed using the constant score preoperatively and postoperatively at
      specific intervals up to 1 year. The greatest improvement in the laser group was
      seen in the areas of pain with activity, pain at night, activity and movement at
      1 week and at 6 weeks. The patients in group L also showed significantly better
      values for abduction power (P < .05). There were no complications in either
      group. Radiographic evaluation with the outlet view, preoperatively and
      postoperatively, showed an adequate bone resection in all cases. The
      postoperative Constant score for group L was significantly better. The average
      score increased from 54.7 to 79.8 in group L and from 50.3 to 68.7 in group S.
      Because of the low level of postoperative pain, the absence of adhesions and the
      almost complete lack of swelling, the patients in group L were able to regain
      full range of shoulder motion sooner than those in group S.

PMID- 8534296
TI  - The relationship between subacromial space pressure, blood pressure, and visual
      clarity during arthroscopic subacromial decompression.
AB  - Twenty-two consecutive patients with subacromial impingement syndrome underwent
      arthroscopic subacromial decompression. Measurements of the subacromial space
      pressure and the blood pressure were recorded along with the clarity of the
      visual field. The clarity of the visual field was objectively determined based on
      the pressure at which bleeding was observed from trabecular bone or the soft
      tissue capillaries. A direct correlation was found between systolic blood
      pressure (SBP), subacromial space pressure (SASP), and the clarity of the visual
      field. On average, maintaining a pressure difference (SBP-SASP) of 49 mm Hg or
      less prevented bleeding and permitted good visualization. With a greater
      differential, significant bleeding occurred. Furthermore, the use of relative
      hypotensive anesthesia permits lower irrigation pressures and significantly
      reduces the risk of fluid extravasation into the subcutaneous tissues of the
      shoulder.

PMID- 8534297
TI  - Arthroscopic Bankart suture repair for recurrent traumatic unidirectional
      anterior shoulder dislocations.
AB  - We report our experience with arthroscopic repair of the Bankart lesion following
      traumatic unidirectional anterior shoulder dislocation. Thirty consecutive
      patients (7 women, 23 men; average age, 26.5 years) were followed for an average
      of 38 months (minimum 2-year follow-up) after arthroscopic Bankart suture repair
      for recurrent shoulder dislocation. The study included patients who had pure
      shoulder dislocations (excluding those with instability secondary to subluxation,
      multidirectional instability, or an atraumatic origin), had experienced an
      initial frank shoulder dislocation (documented radiographically or requiring the
      assistance of medical personnel for reduction), and had a Bankart lesion,
      visualized arthroscopically. Clinical evaluation using the Rowe functional
      grading system showed 11 patients rated as excellent, 8 as good, 3 as fair, and 8
      as poor. Six of 8 patients were rated as poor because they frankly redislocated
      following their arthroscopic shoulder stabilization. Our study shows a 27%
      failure rate in this group. Critical reevaluation of the transglenoid
      arthroscopic Bankart procedure is mandatory to identify the appropriate patient
      population for this procedure.

PMID- 8534298
TI  - Coracoacromial ligament: a comparative arthroscopic and anatomic study.
AB  - An anatomic study of the coracoacromial ligament was conducted. The data
      collected from 20 anatomical preparations and the arthroscopic findings in 40
      cases were compared. The shape and the tension of the ligament were evaluated, as
      well as the thickness. Anatomic tradition describes the ligament as a fibrous
      triangular lamina inserted with its apex on the acromial tip and its base on the
      lateral edge of the coracoid. It simply closes the coracoacromial arch and has no
      mechanical role. However, our observations suggest that the ligament has a
      trapezoidal shape and is situated below the acromion with a wide reflex portion.
      Its thickness varies from 2 to 5.6 mm. Given that structure, the ligament appears
      like a robust suspension structure of the coracoid, which contrasts the action of
      the muscles that connect to it. From these observations, a pathogenic hypothesis
      of the subacromial impingement proposes itself.

PMID- 8534299
TI  - Reliability of the clinical assessment in predicting the cause of internal
      derangements of the knee.
AB  - The reliability of the clinical assessment, which comprised history, physical
      examination, and plain radiographs, was determined by comparing the initial
      preoperative diagnosis with the postoperative diagnosis as determined
      arthroscopically, and by comparing the results of the clinical evaluation with
      published reports of arthrography, computed tomography (CT), and magnetic
      resonance imaging (MRI). The study group included 206 patients (216 knees)
      scheduled for arthroscopic surgery for suspected internal derangements. The
      primary preoperative clinical diagnosis was correct in 175 knees (81%), with an
      overall accuracy of 93%, sensitivity of 89%, and specificity of 94%. The most
      common preoperative diagnoses were medial and lateral meniscal tears. Results of
      the clinical assessment were comparable or superior to published reports of
      arthrography, CT, and MRI. Thus, it may be unnecessary to routinely use these
      costly special studies to determine the need for arthroscopic surgery. We
      conclude that a thorough clinical assessment can provide sufficient information
      for the surgeon to make a definitive primary preoperative diagnosis, and that
      arthroscopy should not be performed without first completing a complete
      preoperative examination.

PMID- 8534300
TI  - Endoscopic anterior cruciate ligament reconstruction: modified technique and
      radiographic review.
AB  - The original technique for endoscopic anterior cruciate ligament reconstruction
      has several potential complications because of constraints imposed by working
      through the tibial tunnel: improper femoral tunnel placement, violation of the
      femoral tunnel posterior wall, femoral interference screw divergence, graft
      laceration during screw insertion, and distal tibial bone block protrusion. We
      performed 100 consecutive endoscopic anterior cruciate ligament reconstructions
      with bone-tendon-bone autograft using a modified technique that minimizes each of
      these problems through the use of an accessory medial parapatellar portal.
      Postoperative radiographic review showed femoral screw divergence in only 9% of
      cases (average angle, 6.9 degrees), all in the anteroposterior plane. The tibial
      tunnel was drilled at an average of 66 degrees to the plateau and averaged 52 mm
      in length. There was no graft damage during screw insertion or protrusion of the
      bone blocks. We conclude that this modified technique allows simplified,
      reproducible tunnel and interference screw placement.

PMID- 8534301
TI  - Technique and clinical evaluation of arthroscopic ankle arthrodesis.
AB  - Arthroscopic ankle arthrodesis has recently been shown to be an effective
      procedure with significant advantages when properly indicated. We report on the
      results of arthroscopic ankle fusion in 16 patients with idiopathic or
      posttraumatic osteoarthritis and rheumatoid disease. We used standard ankle
      arthroscopic technique and simple noninvasive distraction with hanging weights.
      All 16 patients had a successful fusion at an average of 9.5 weeks
      postoperatively. Complications included 1 lateral cutaneous neuroma, and 1
      patient who required removal of screws because of superficial pain. Postoperative
      evaluation showed complete resolution of pain in 14 of 16 patients and
      significant improvement in gait. Fourteen of 16 patients were completely
      satisfied with the result and cosmesis, and only 1 patient required shoe
      modification. These results substantiate previous reports that arthroscopic ankle
      arthrodesis is successful, and where indicated, has significant advantages over
      the open technique.

PMID- 8534302
TI  - Fluid pump systems for arthroscopy: a comparison of pressure control versus
      pressure and flow control.
AB  - We set out to compare two pump systems, one in which pressure alone could be
      controlled and the second in which pressure and flow could be controlled
      separately. Assessments were carried out by two observers independently. A
      variety of arthroscopic procedures were studied including arthroscopy of the
      knee, anterior cruciate ligament reconstruction, arthroscopy and acromioplasty of
      the shoulder, and arthroscopy of the elbow and ankle. We found that both systems
      used a similar amount of fluid. However, the operative time was significantly
      decreased with separate control of pressure and flow. This was related to the
      fact that there was better visualization and better technical ease with the
      latter pump. There was significantly less extravasation in the soft tissues.
      Therefore, based on our assessment, pumps that separately control pressure and
      flow are significantly better than pumps that control pressure alone. There is
      distinct advantage in less operative time, greater visualization, technical ease,
      and less soft tissue extravasation.

PMID- 8534303
TI  - Comparison of pullout strength for seven- and nine-millimeter diameter
      interference screw size as used in anterior cruciate ligament reconstruction.
AB  - This study compares biomechanical properties of 7- and 9-mm diameter screws
      providing interference fixation in anterior cruciate ligament reconstruction.
      Sixteen pairs of fresh-frozen bovine knees were evaluated. Uniaxial load to
      failure was performed at a deformation rate of 30 mm/s along the mechanical axis
      of the ligament graft with the knees secured at 45 degrees of flexion in a custom
      jig. A video analyzer was used to measure ligament strain and bone-to-bone
      deformation. Ultimate force, deformation, and failure mode were recorded and
      compared. The 7-mm screws provided 98% yield strength, and 95% ultimate force
      compared with the 9-mm screws. The average femoral pullout strength was 1161 +/-
      93 N in the 7-mm group and 1198 +/- 142 N in the 9-mm group. Failure mode was
      similar in both groups. Clinically, the usage of 7-mm screws may reduce
      iatrogenic injuries to the patellar tendon graft compared with larger screws.
      This study shows that the biomechanical advantages of 9-mm screws compared with 7
      mm screws are minimal.

PMID- 8534304
TI  - Humeral avulsion of glenohumeral ligaments as a cause of anterior shoulder
      instability.
AB  - The avulsion of the glenohumeral ligament labral complex at the glenoid (Bankart
      lesion), as well as ligamentous laxity are well known causes of anterior shoulder
      instability. A lesser known entity, the humeral avulsion of glenohumeral
      ligaments (HAGL), was studied to determine its incidence and its role in anterior
      glenohumeral instability. Sixty-four shoulders with the diagnosis of anterior
      instability were prospectively evaluated by arthroscopy for intraarticular
      pathology, including Bankart, capsular laxity, and HAGL lesions. Six shoulders
      were found to have HAGL lesions (9.3%), 11 shoulders with generalized capsular
      laxity (17.2%), and 47 shoulders with Bankart lesions (73.5%). In patients with
      documented anterior instability without a demonstratable "primary" Bankart
      lesion, a HAGL lesion should be ruled out. This lesion is readily recognized
      arthroscopically, and an appropriate repair of this lesion can restore anterior
      stability to the patient. The pathological anatomy of the HAGL lesion and our
      treatment of this lesion is discussed.

PMID- 8534305
TI  - Intraarticular fibroma of the tendon sheath of the knee.
AB  - Fibroma of the tendon sheath is an uncommon soft-tissue tumor. Intraarticular
      localization has not been previously reported. The patient presented with
      unexplained recurrent swelling of the knee not associated with recent trauma. The
      soft-tissue tumor was identified by magnetic resonance imaging. Arthroscopy
      confirmed the diagnosis. Arthrotomy was performed because of the large size of
      the lesion.

PMID- 8534306
TI  - Symptomatic ganglion cyst within the substance of the anterior cruciate ligament.
AB  - Many previous investigators have reported the findings of ganglion cysts on the
      surface of the anterior cruciate ligament. The cysts reported in the literature
      were either symptomatic or only of incidental findings. So far, however, there
      has not yet been a report of a ganglion cyst within the substance of the anterior
      cruciate ligament. This is the first report of a ganglion cyst within the
      substance of the anterior cruciate ligament, which caused intermittent swelling
      and pain in the right knee of a 13-year-old girl without any history of trauma.
      The cyst was treated successfully with an arthroscopic debridement and
      arthroscopically guided needle aspiration.

PMID- 8534307
TI  - An unusual case of vascular abnormality mimicking a lateral meniscal cyst.
AB  - An unusual case of a vascular abnormality mimicking a lateral meniscal cyst is
      reported. The patient was a 31-year-old active sportsman who presented with
      intermittent pain over the lateral aspect of the left knee joint line, occurring
      only during activities involving twisting motions such as playing soccer. He did
      not experience local tenderness or swelling, clicking, locking, or giving way.
      The magnetic resonance imaging, which was done after a diagnostic arthroscopy
      with normal intra-articular findings, showed a cyst formation of approximately 4
      mm diameter adjacent to the lateral meniscus periphery, but no meniscal tissue
      degeneration. Exactly at the preoperatively marked site of most intensive pain
      sensation during twisting motions, surgical exposure showed a venous-aneurysm
      like tumor, which was removed. The operation resulted in complete relief of
      symptoms and undisturbed sporting activities including soccer.

PMID- 8534308
TI  - Tourniquet-induced tibial nerve palsy complicating anterior cruciate ligament
      reconstruction.
AB  - In this case report, an unremarkable anterior cruciate ligament reconstruction is
      complicated by a tourniquet-induced tibial nerve palsy. The case underscores the
      necessity of being aware of the potential for complications associated with
      tourniquets, despite following recommended guidelines of tourniquet time and
      pressure.

PMID- 8534309
TI  - The arthroscopic appearance of lipoma arborescens of the knee.
AB  - Lipoma arborescens is a rare intra-articular lesion consisting of a villous
      lipomatous proliferation of the synovial lining. This case report draws attention
      to the history, physical findings, and arthroscopic appearance of lipoma
      arborescens, a rare lesion of the synovial lining of the knee. Arthroscopically,
      the lesion appears as a synovial lesion with numerous fatty-appearing globules
      and villous projections. In addition, magnetic resonance imaging is a valuable
      tool to differentiate the lesion from rheumatoid arthritis, pigmented
      villonodular synovitis, and synovial chondromatosis in those patients who present
      with a chronic, swollen, and painful joint.

PMID- 8534310
TI  - Isolated rupture and repair of the popliteus tendon.
AB  - The authors report the case of a 21-year-old woman who sustained a femoral
      avulsion of the popliteus tendon in a motor vehicle accident. The posterolateral
      injury was suspected on physical examination and confirmed by magnetic resonance
      imaging and arthroscopic examination. The popliteus tendon was repaired using two
      suture anchors. Mild clinical instability was present initially and resolved
      postoperatively. No residual pain, weakness, or posterolateral instability was
      noted.

PMID- 8534311
TI  - Distraction for ankle arthroscopy.
AB  - Distraction has proven to be usefull for arthroscopic visualisation and
      instrumental access to some ankle pathology. A distraction technique using a
      single calcaneal pin combined with the installation of the patient on a fracture
      table is described. The method has already been used by the authors in more than
      100 ankle arthroscopy procedures without distraction-related complications.

PMID- 8534312
TI  - New Frontiers in the Biochemistry and Biophysics of Stroke, Neurotrauma, and
      other Neurological Diseases. Papers from the 6th International Symposium. Martin,
      Slovak Republic, August 16-19, 1993.

PMID- 8534313
TI  - Brainstem auditory evoked potentials (BAEPs) pathology in topographical diagnosis
      of posterior fossa lesions.
AB  - The authors tried to determine the level of the brainstem where possible
      generators of various BAEPs waves could be situated by correlating clinical
      neurological symptomatology and/or cranial computed tomography findings of 195
      patients with posterior fossa lesions with distinct BAEPs waves pathology.
      Results of statistical analysis showed a significant dependence between the
      levels of lesions as revealed by clinical symptomatology and/or cranial computed
      tomography and distinct BAEPs waves I-V pathology. Only indirect proof exists for
      the supratentorial origin of waves VI and VII. Because of the frequently normal
      function of hearing, as revealed by routine audiometry, in every group of
      patients with distinct BAEPs waves pathology, the authors also suggest that
      structures not involved in behavioral mechanisms of hearing could participate in
      BAEPs waves generation.

PMID- 8534314
TI  - Experimental studies of some microrheological factors in serious brain ischemia
      after stobadine pretreatment.
AB  - Serious brain ischemia was induced by occlusion of cerebral arteries in dogs. The
      occlusion time was 7 min. The blood was collected at various intervals of
      reperfusion (5, 60, 180, 240 min and 24 h). Thirty minutes before ischemization,
      stobadine was given (1, 2, or 5 mg/kg). The changes of erythrocyte membrane
      fluidity were evaluated using colloid-osmotic hemolysis induced by brilliant
      cresyl blue. In the control group (without stobadine) the colloid-osmotic
      hemolysis was significantly increased immediately after ischemization and after 5
      and 60 min. However, after 240 min of reperfusion, a significant decrease of
      hemolysis was observed. The increase of colloid-osmotic hemolysis after
      ischemization in the control group was prevented after stobadine pretreatment.
      The thrombotization of microcirculation that was observed in the control group
      was not present after stobadine pretreatment.

PMID- 8534315
TI  - Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of
      rabbits exposed to brain ischemia and reperfusion.
AB  - Changes in the functioning of the glutamatergic system in rabbit brain were
      studied after partial brain ischemia and reperfusion. In vitro studies were
      conducted relating to the release of L-[14C]glutamate from cortical brain slices,
      L-[14C]glutamate uptake in synaptosomes, and 45Ca uptake in synaptosomes. It was
      found that basal release of L-[14C]glutamate from rabbit brain cortical slices
      after 30 min of partial ischemia and 1 d of reperfusion was essentially without
      change compared to the control values. After 3 d of reperfusion, there was an
      increase in basal release of L-[14C]glutamate from rabbit brain cortical slices.
      K+ stimulated release of L-[14C]glutamate in normal Krebs-Ringer medium was
      essentially the same in the control group and in the experimental group after 30
      min of ischemia. The K+ stimulated release of L-[14C]glutamate independent of
      calcium was increased to 145% after 30 min of ischemia and 1 d of reperfusion.
      The decreased Km value at the glutamate transporter may have contributed to this
      difference. Kinetic parameters of the L-[14C]glutamate uptake (Km and Vmax) in
      synaptosomes from rabbit brain were significantly lower after 30 min of ischemia.
      The authors discovered that during the reperfusion period, Vmax was almost the
      same as in the control group. The activity of the Na+/Ca2+ exchanger in
      synaptosomes of rat brain was about 70% of the control values after 30 min of
      ischemia and 72 h of reperfusion. According to our results, increased L
      [14C]glutamate release after 30 min of ischemia appears to be the result of
      higher intracellular calcium concentration and possibly also of a higher uptake
      of glutamate.

PMID- 8534316
TI  - Relative resistance of rabbits to MPTP neurotoxicity.
AB  - The neurotoxic actions of MPTP and its 4-(O-tolyl) analog (2'-Me-MPTP) on two
      breeds of rabbits were investigated. MPTP, but not 2'-Me-MPTP, causes a reduction
      (about 40%) in striatal dopamine content in rabbits of the "little silver-black"
      breed. The dopamine content of striata of "chinchilla" rabbits was not affected
      by either agent.

PMID- 8534317
TI  - Postischemic reperfusion causes a massive calcium overload in the myelinated
      spinal cord fibers.
AB  - The visualization of Ca binding in the myelinated axons of lumbosacral segments
      of rabbit was done at the electron microscopic level using the spinal cord
      ischemia model. To assess the calcium accumulation, the binding agent
      pyroantimonate was used. Nonsignificant Ca2+ binding was found in the myelinated
      axons after 40 min of ischemia followed immediately by perfusion fixation. A high
      concentration of calcium pyroantimonate deposits, seen as electron dense
      particles, was detected in the myelin interlamellar clefts and axoplasm. The
      paranodal region was the most affected site.

PMID- 8534318
TI  - Breakdown of membrane phospholipids in Alzheimer disease. Involvement of
      excitatory amino acid receptors.
AB  - Membrane phospholipids are not only essential membrane constituents but also
      determine many membrane functions and integrity. Normal receptor function, signal
      transduction, and transport of essential substrates depend strongly on normal
      membrane phospholipid metabolism. Studies of plasma membrane phospholipid
      composition have indicated that ethanolamine glycerophospholipids decrease,
      whereas serine glycerophospholipids increase significantly, in Alzheimer disease
      (AD). The release of arachidonate from the sn-2 position of glycerophospholipids
      is catalyzed by phospholipases and lipases. These enzymes are coupled to EAA
      receptors. Overstimulation of these receptors may be involved in abnormal calcium
      homeostasis, degradation of membrane phospholipids, and the accumulation of free
      fatty acids, prostaglandins, and lipid peroxides. Accumulation of the mentioned
      metabolites, as well as abnormalities in signal transduction owing to stimulation
      of lipases and phospholipases, may be involved in the pathogenesis of the
      neurodegeneration in AD.

PMID- 8534319
TI  - Plasma membrane Ca(2+)-pump functional specialization in the brain. Complex of
      isoform expression and regulation by effectors.
AB  - The plasma membrane Ca(2+)-pump (PMCA) is a key element in the removal of
      intracellular Ca2+. A number of PMCA pumps, encoded by a multigenic family and
      differing in their regulatory domains, also exist in the neuronal cells. We
      discuss here an idea regarding a new, higher level of specialization of PMCA
      protein isoforms with different sensitivities toward phospholipids and
      calmodulin. The idea is based on the kinetic data from PMCA stimulation by acidic
      phospholipids, with a combination of results describing an alternative RNA
      splicing at site A and C coding of regulatory domains of protein. The resulting
      complex modulation of the Ca(2+)-pump underlies the specific cellular
      requirements for Ca2+ homeostasis in a tissue-selective manner and is regulated
      by the level and spatial distribution of enzyme isoforms as well as by the level
      of their regulatory factors. The possible role of PMCA protein in the neuronal
      injury is also discussed.

PMID- 8534320
TI  - Short-term postischemic hypoperfusion improves recovery of protein synthesis in
      the rat brain cortex.
AB  - A cell-free system from rat brain cortex was used to follow changes in protein
      synthesis after ischemia and reperfusion (four-vessel occlusion). The experiment
      was focused to prevent a violent burst of free oxygen radicals creation during
      the first period of postischemic reperfusion by short-term hypoperfusion. After
      30 min of ischemia, the authors applied hypoperfusion produced by releasing one
      (right) carotid for the first 5 min of reperfusion lasting from 30 min to 3 d.
      Results obtained by this procedure show that the activity of protein synthesis
      machinery from hypoperfused brains is higher than normovolemic ones; the left
      hemisphere, which is contralateral to direct blood flow during hypoperfusion,
      shows better results than the right hemisphere.

PMID- 8534321
TI  - Protective effect of stobadine, a pyridoindole antioxidant, in hypoxia
      reoxygenation injury of ganglionic and hippocampal neurotransmission.
AB  - Hypoxia (HYP) followed by reoxygenation (REOX) occurs frequently in the
      pathophysiology of the CNS. Free oxygen radicals (FOR) may participate in
      cerebral injury under such circumstances. Pharmacological control of the
      generation and/or subsequent effects of FOR by new effective compounds might
      contribute to the treatment of disorders such as stroke and cerebral trauma.
      Effects of stobadine, a pyridoindole antioxidant that is able to interact with
      some FOR, were analyzed on synaptic transmission in rat superior cervical ganglia
      and hippocampal slices during HYP-REOX procedure in vitro. The amplitude of
      compound action potential in the ganglion evoked by supramaximal electrical
      stimulation of preganglionic nerve was reduced to approximately 20% of the
      control value during HYP (90 min). The action potential did not recover during
      REOX (60 min). Stobadine (10 mM) applied before, during, and after HYP, did not
      change the HYP-induced inhibition; however, a significant recovery of
      transmission (to 78.5% +/- 8.3) occurred during REOX. A similar effect was
      observed in the presence of the antioxidant Trolox (0.2 mM), a derivative of
      alpha-tocopherol. Stobadine, in concentrations of > 30 microM inhibited
      ganglionic transmission in a concentration-dependent manner. HYP lasting more
      than 2-3 min fully depressed field action potentials evoked in hippocampal CA1
      region neurons by supramaximal electrical stimulation of Schaffer collaterals. If
      HYP exceeded 8 min, transmission did not recover during REOX. Stobadine (10
      microM) applied during HYP significantly enhanced the probability of transmission
      recovery in the REOX period. Some preparations recovered following HYP lasting as
      long as 13-15 min. On applying the compound before, during, and after HYP that
      lasted for 8 min, the transmission recovery was 72.6% +/- 21.8 of the control
      value, compared to only 16.1% +/- 12.7 in the untreated preparations. In
      concentrations ranging from 0.3-1.73 mM, stobadine inhibited hippocampal
      transmission. Stobadine proved to be an effective agent in the protection of
      synaptic transmission against HYP-REOX-induced injury in both neuronal
      preparations studied in vitro. This effect might be linked to the antioxidant and
      free radical scavenging effects of stobadine.

PMID- 8534322
TI  - Central stimulation of hormone release and the proliferative response of
      lymphocytes in humans.
AB  - The central nervous system (CNS) may communicate with the immune system by direct
      innervation of lymphoid organs and/or by neurotransmitters and changes in
      neuroendocrine functioning and hormone release. The consequences of selective
      transient changes in circulating hormones on immune functioning in humans have
      not yet been studied. To address this problem, the authors evaluated the
      lymphoproliferative responses to optimal and suboptimal concentrations of
      phytohemagglutinin (PHA) and pokeweek mitogen (PWM) under selective enhancement
      of circulating growth hormone, prolactin, or norepinephrine. The authors failed
      to demonstrate any effect of elevated growth hormone levels after clonidine
      challenge on the lymphoproliferative response to mitogens. Similarly, the results
      did not show any effect of elevated prolactin concentrations induced by
      domperidone administration on the immune test. Exposure of volunteers to cold
      resulted in elevation of plasma norepinephrine levels without changes in growth
      hormone, epinephrine, or cortisol secretion. Cold exposure induced elevation of
      plasma norepinephrine and reduction of the lymphoproliferative response to the
      suboptimal dosage of PHA. The reduction was significant 180 and 240 min after
      exposure. These results are indicative of a relationship between norepinephrine
      and immunity.

PMID- 8534323
TI  - Quantitative analysis of myelinated nerve fibers of peripheral nerve in
      streptozotocin-induced diabetes mellitus.
AB  - The purpose of this study was to examine morphometric changes of myelinated
      fibers in early stages of experimental diabetes mellitus. Adult male Wistar rats
      aged 17 wk were used in this study. Diabetes mellitus was induced by
      streptozotocin. Samples of common peroneal nerve from diabetic rats (4 and 8 wk
      after induction of diabetes mellitus) and age-matched control animals were
      removed and processed. The semithin cross sections were stained with toluidine
      blue and used for myelinated fiber computer-aided morphometric analysis. There
      were no significant changes in diabetic animals after 4 wk duration of the
      disease. There was significant reduction in myelinated nerve fiber caliber in
      diabetic rats 8 wk after induction of diabetes as compared to age-matched
      controls. There was no significant reduction of axonal area in this group of
      diabetic rats, so diminution of fiber area was caused predominantly by reduction
      of myelin sheath area. The study demonstrates that the induction of diabetes
      mellitus in rat by streptozotocin is accompanied by early changes of the
      morphometric indices of myelinated nerve fibers of peripheral nerve.

PMID- 8534324
TI  - Immunohistochemical detection of cells labeled with bromodeoxyuridine after
      neural transplantation.
AB  - Pregnant rats were treated with 5-bromo-2'-deoxyuridine (BrdU) from embryonic d
      12 (ED12) to ED14. BrdU administration allowed timed labeling of dividing
      embryonic cells in utero, since the drug is incorporated into the DNA in place of
      thymidine during the S-phase of the cell cycle. ED14 rat cerebral cortex or
      placenta was grafted into the brain of adult rats. Anti-bromodeoxyuridine
      immunohistochemistry was used for identifying labeled transplanted cells after
      different survival periods in paraffin-embedded sections. BrdU labeled cells were
      observed in both intraventricular and intraparenchymal cortical grafts, even
      after a 3-mo survival. Although the percentage of positive cells decreased in
      comparison with ED14 cortex, the level of BrdU (i.e., the intensity of anti-BrdU
      immunohistochemistry) in labeled nuclei was probably the same. BrdU pretreatment
      of ED14 cells prior to grafting did not affect the proliferative ability of the
      grafted tissue. In ED14 placental grafts, all trophoblastic cells were labeled
      distinctly. This precise labeling technique enabled an examination of individual
      migrating trophoblastic cells. However, migration of these cells into the host
      brain was very limited.

PMID- 8534325
TI  - Mathematical methods using CT and MR images for stereotactic neurosurgery.
AB  - A new application area in the practical usage of magnetic resonance imaging (MRI)
      has been identified as a methodology of stereotactic operation. In particular,
      our approach provides a solution for the straightforward definition of target and
      trepanation points for the purposes of stereotactic neurosurgical operation, and
      an exact testing of its result. The definition of the proper transformation
      between different examination data sets is a crucial mathematical problem. This
      is well done by morphing and the thin plate spline method.

PMID- 8534326
TI  - Hypoxic hypoxia induces different biochemical changes in the cortex of the right
      and left hemispheres of rat brain.
AB  - The activity of acetylcholinesterase (AChE), adenylate cyclase (AC), 5'
      nucleotidase (NT), Na+, K(+)-ATPase, as well as the contents of phospholipids
      (PL) and gangliosides (G) per mg of protein in homogenate, crude membrane (P2)
      fraction, and synaptosomes from the sensorimotor cortex of the right and left
      hemispheres of rat brain were analyzed under normal and hypoxic conditions. The
      authors found that under normal physiological conditions there are no significant
      differences of the studied parameters in homogenates of sensorimotor cortex from
      the right and left hemispheres. In P2 fractions, and especially in preparations
      of synaptosomes from the right and left cortex, differences in the activity of 5'
      NT and AC were found. Hypoxia (pO2 = 7.8%) was shown to alter studied parameters
      (AChE, AC, Na+, K(+)-ATPase activity, and PL content) mainly in the right
      hemisphere.

PMID- 8534327
TI  - Late responses after transcranial magnetic stimulation in stroke.
AB  - In addition to early responses after transcranial magnetic stimulation, usually
      designated as Motor Evoked Potentials (MEP), several late responses have been
      reported in intervals up to 500 ms following stimulus. Our attention in this work
      was focused on the response in interval 150-300 ms after stimulus output, which
      is also designated as S > 150 response. We monitored longitudinally late S > 150
      response in group of 19 stroke patient with verified hemispherical ischemic
      lesion. Our results have shown that the presence of late S > 150 response on the
      first day after stroke predicts an excellent improvement of clinical deficit and
      that late S > 150 response is more sensitive to hemispheric lesion than early
      MEPs. From this point of view, recording of late responses can supplement early
      MEP recording. Our study demonstrated that supratentorial structures are involved
      in the origin of the S > 150 response. According to the observation that in some
      patients a normal early response was present and an S > 150 response was absent
      on the hemiparetic side, and both responses were present on the unaffected side,
      we hypothesize that cortical structures play an important role in S > 150
      response.

PMID- 8534328
TI  - Region distribution of the gangliosides in rat brain after chronic ethanol
      treatment.
AB  - In this study the effects of chronic ethanol administration on the regional
      distribution of brain gangliosides were investigated. A total of 36 60-d-old male
      Wistar rats weighing approximately 200 g was divided into two groups of 18
      animals each. The ethanol-consuming group was offered drinking fluid (25% sucrose
      32% ethyl alcohol, w/w) ad libitum, and the control group was given a sucrose
      solution isocaloric with the ethanol-sucrose solution. After 6 mo of chronic
      ethanol treatment, cerebral cortex, N. caudatus, hypothalamus, thalamus, and
      hippocampus were analyzed with respect to their ganglioside pattern (GM2, GM1,
      GD1a, GD1b, GT1b, and GQ). The results showed that there were highly significant
      effects of ethanol on hypothalamus GD1b and GT1b, thalamus GM1 and GD1a, and
      hippocampus GM1, GD1b, and GT1b ganglioside distribution. It was found that
      ethanol differently affected the gangliosides in these brain regions.

PMID- 8534329
TI  - Epidural perfusion cooling protects against spinal cord ischemia in rabbits. An
      evaluation of cholinergic function.
AB  - The protective effect of regional epidural spinal cord cooling was evaluated in a
      rabbit spinal cord ischemia model. Hypothermia was performed by the continual
      perfusion of 2-4 degrees C cold saline in the epidural space around the ischemic
      lumbar segments, 4 min before and during ischemia. The spinal cord was deeply
      hypothermic (21 degrees C) throughout the whole ischemic period. Ischemia was
      induced by the occlusion of the abdominal aorta for 40 min under normothermic or
      hypothermic conditions. Recovery of motor and sensory functions, spinal cord
      evoked potentials, and motor-evoked potentials were then evaluated up to 24 h
      postischemia. After this period, choline acetyltransferase (ChAT) and
      acetylcholinesterase (AChE) activities were measured, in particular, zones of the
      lumbar spinal cord. AChE was also investigated histochemically. Animals in the
      normothermic group displayed fully developed spastic paraplegia with near
      complete loss of spinal somatosensory and motor-evoked potentials. AChE
      histochemistry showed extensive necrotic changes affecting lumbosacral gray
      matter. These changes corresponding with the pronounced losses of ChAT and AChE
      activities indicated irreversible injury of the spinal cord. In contrast, after
      hypothermic ischemia, animals survived without any sign of neurological
      impairment with almost full recovery of the spinal cord-evoked potentials. ChAT
      and AChE activities in the gray matter showed near control values corresponding
      with histochemical analysis of fully preserved gray matter. Hypothermia under the
      present experimental conditions efficiently protected the spinal cord against
      ischemic injury.

PMID- 8534330
TI  - Effect of a combination of pentoxifylline and nimodipine on lipid peroxidation in
      postischemic rat brain.
AB  - The authors studied the effects of a combination of pentoxifylline and nimodipine
      on cerebral lipid peroxidation in postischemic rat brain. Pentoxifylline (40
      mg/kg) and nimodipine (3 mg/kg) were administered per os 30 min before 5 min of
      ischemia (four-vessel occlusion model of transient ischemia). The extent of
      peroxidation in brain tissue (cerebral cortex, hippocampus, striatum) was then
      estimated by assay of thiobarbituric acid reactive substances (TBARS). The
      concentration of TBARS was significantly lower in the cerebral cortex and
      hippocampus of the group treated with the combination of drugs than in untreated
      ischemic rats. However, this concentration was not significantly different from
      that found in the cerebral cortex and hippocampus of other groups premedicated
      with nimodipine or pentoxifylline alone. The tested drugs had no effect on TBARS
      in the striatum. The hypothesis that the combination of drugs would have a
      synergistic effect on postischemic lipid peroxidation was therefore not
      confirmed.

PMID- 8534331
TI  - Histometric texture analysis of DNA in thin sections from breast biopsies.
      Application to the detection of malignancy-associated changes in carcinoma in
      situ.
AB  - OBJECTIVE: To evaluate histometric measurement of nuclear texture in breast
      biopsy sections in order to detect malignancy-associated changes in apparently
      normal tissue in the vicinity of carcinoma in situ. STUDY DESIGN: We previously
      showed that image cytometry measurements of nuclear features--foremost, texture
      features, describing the organization of Feulgenstained DNA in the cell--can be
      used to distinguish normal-appearing, diploid epithelial cells from patients with
      invasive carcinoma of the breast from those with benign biopsies. In that study,
      referred to as the "single cell analysis," images of at least 200 epithelial
      cells were acquired for each slide, and substantial user interaction was required
      to segment cells from each field. Location of isolated cells and interactive
      segmentation are both time-consuming procedures, particularly in breast tissue,
      where nuclei can be tightly clustered within a duct. With histometric texture
      analysis on the same specimens, segmentation of individual cells was ignored, and
      texture measurements were performed over the entire cluster of relevant cells.
      With this approach, ploidy information is not available, and touching and
      overlapping nuclei are included in the measurements. Measurement of histometric
      texture properties requires substantially less time (at least an order of
      magnitude) than individual cell measurement and, if ploidy information is not
      significant, may therefore provide a more practical means of analysis for tissue
      sections. RESULTS: Seventeen cases of invasive carcinoma and 17 cases of
      nonproliferative breast disease were examined. Using stepwise discriminant
      function analysis, slides were classified into one of the two groups with an
      accuracy of 88.6% in the case of single cell analysis and with an accuracy of
      88.2% using histometric analysis. CONCLUSION: The existence of malignancy
      associated changes in the breast was confirmed by an independent analysis of the
      same specimens. Although the two methods are not directly comparable, we found
      that histometric texture analysis performs at least as well as single-cell
      analysis for the detection of malignancy-associated changes in breast carcinoma.

PMID- 8534332
TI  - Management of uncertainty in breast cancer grading with Bayesian belief networks.
AB  - OBJECTIVE: To examine the potential of different constructs of Bayesian belief
      networks (BBN) to manage uncertainty in breast cancer grading. STUDY DESIGN: We
      developed four networks, two based on Bloom-Richardson's and two on Helpap's
      grading systems. The function of the networks was based either on an expert's
      experience or frequency counts derived from subjective grading of a large number
      of samples. The four BBNs were tested on 20 specimens, and the resulting final
      beliefs were compared with the subjective gradings. RESULTS: The BBNs showed
      agreement with the subjective gradings in 60-85% of cases. Different constructs
      of BBNs, however, differed in their performance. The mean beliefs in frequency
      based networks were slightly higher than in experience-based networks. In
      addition, as compared with the Bloom-Richardson-based networks, the Helpap-based
      BBNs resulted in higher maximum beliefs but produced a larger fraction of
      discrepancies with the subjectively graded cases. Depending on the type of
      network, 65-90% of the BBN grades were associated with high beliefs. CONCLUSION:
      The results suggest that for reliable results, grading systems with more than
      three or four variables may be necessary. When based on relevant information,
      BBNs seem to have the potential to become a valuable method of assisting the
      pathologist in breast cancer grading.

PMID- 8534333
TI  - Flow cytometric DNA measurements in aspiration biopsies and surgical specimens of
      breast cancer.
AB  - OBJECTIVE: One of the prognostic factors in breast cancer is the proliferation
      activity of the tumor. This study sought knowledge of this activity before
      surgery to benefit the design and timing of therapy. STUDY DESIGN: Flow
      cytometric DNA analysis data from 52 diagnostic fine needle aspirates were
      compared with data from subsequent surgical specimens. RESULTS: The data showed
      that the coefficient of variation of the G1 peak was lower in the aspirates.
      Small, near-diploid peaks were detected more frequently in aspirate histograms
      than in surgical specimens. DNA analyses by flow cytometry from aspirates, which
      can be obtained prior to surgical treatment, were as reliable as those obtained
      from surgical specimens, provided that the cellular material was diagnostic of
      cancer. CONCLUSION: Our results suggest that flow cytometry DNA analysis from the
      first preoperative cytologic specimen from a breast tumor will permit faster
      planning and coordination of breast cancer care.

PMID- 8534334
TI  - Image segmentation of cribriform gland tissue.
AB  - OBJECTIVE: To develop procedures for the segmentation of cribriform prostatic
      glands. STUDY DESIGN: A knowledge-guided procedure following a model-based
      reasoning process was developed in the context of a set of interacting expert
      systems for machine vision in histometry. RESULTS: With 78 entities in the
      knowledge file, fully automated, correct segmentation of approximately 70-80% of
      cribriform glands was attained--i.e., outlining of histologic components agreed
      with visual assessment. Measurement of gland size, shape, lumen area, number of
      lumina per gland, epithelial layer thickness, degree of cribriformity and
      determination of completeness of lining of a gland by a basal cell layer could be
      taken from the correctly segmented images. CONCLUSION: The automated procedure
      allows a histometric characterization of premalignant and malignant prostatic
      lesions. Extension of system capabilities to the utilization of spectral
      information is expected to allow an increase in the correct segmentation rate.

PMID- 8534335
TI  - Chromatin texture analysis in three-dimensional images from confocal scanning
      laser microscopy.
AB  - OBJECTIVE: Three-dimensional (3D) images of tissue blocs can be obtained through
      optical sectioning by a confocal scanning laser microscope and by piling up of
      consecutive confocal planes. These images offer the opportunity to quantitate
      biologic structures (i.e., nuclear chromatin) in 3D. Chromatin texture analysis
      is regarded as a key element in nuclear grading of malignant lesions. The present
      study introduced a new method of structural texture analysis of 3D chromatin
      distribution in cell nuclei. The method was assessed for its validity in a pilot
      study. STUDY DESIGN: The study group consisted of 300 3D cell nuclei from
      prostatic lesions, 100 each of hyperplasia, dysplasia and well-differentiated
      carcinoma. A set of 15 texture features was studied for its classification
      capability in a discriminant analysis. RESULTS: A classifier that confined three
      texture features yielded a classification accuracy of 91.7% for the training set
      (60 nuclei). The classification accuracy for the test set (240 nuclei) was 93.3%.
      CONCLUSION: The new method demonstrated its potential for 3D chromatin analysis.
      Further studies on large numbers of cases are necessary to evaluate the use of 3D
      nuclear grading for diagnostic pathology.

PMID- 8534336
TI  - Stereotactic biopsies from astrocytic tumors. Diagnostic information contributed
      by the quantitative chromatin pattern description.
AB  - OBJECTIVE: To reduce the problem of heterogeneity in astrocytic tumors by means
      of computer-assisted microscope analysis of Feulgen-stained nuclei. STUDY DESIGN:
      Thirty-eight glial tumors for which we obtained 227 stereotactic biopsies were
      subjected to digital cell image analysis of Feulgen-stained nuclei. This series
      of 38 glial tumors included 36 supratentorial astrocytic tumors (13 astrocytomas,
      7 anaplastic astrocytomas and 16 glioblastoma multiformes) and 2 grade 3
      astrocytic tumors of the cerebellum. RESULTS: The results suggest a new
      methodology, enabling the biologic characteristics of the brain parenchymal area
      surrounding a given glial tumor to be characterized. This methodology relies on
      the performance of three successive steps. The first is quantitative
      characterization of nuclear morphology and its chromatin pattern by means of 15
      morphonuclear variables. This characterization is carried out by means of the
      computer-assisted microscope analysis of Feulgen-stained nuclei. The second step
      consists of setting up morphonuclear data banks, with each process giving the
      precise portrait of a given cell nuclear population. This process is carried out
      by means of multivariate analysis, taking into account the 15 variables mentioned
      above. Multivariate analysis includes principal components analysis followed by
      the canonical transformation of the data. The third step consists of testing
      unknown cases against these morphonuclear data banks. This is carried out by
      means of linear discriminant analysis, which enables the various cell nuclear
      types in the stereotactic biopsy to be quantified. CONCLUSION: The present
      methodology makes it possible to investigate whether infiltrating tumor cells are
      present in or absent from the parenchymal brain area surrounding a glial tumor.
      It can therefore contribute additional information to that contributed by
      computed tomography and/or magnetic resonance imaging with respect to the precise
      delineation of the volume of a brain tumor. This delineation must be as precise
      as possible to allow total surgical resection of the tumor and prevention of its
      recurrence.

PMID- 8534337
TI  - Bleaching of melanin before image cytometry of the DNA content of pigmented skin
      tumors.
AB  - OBJECTIVE: To study the effect of bleaching of melanin with KMnO4 on the results
      of DNA image cytometry in pigmented skin tumors. STUDY DESIGN: Image cytometry of
      nuclear DNA content was performed on sections from 14 melanocytic skin tumors
      stained with Feulgen stain both with and without prior bleaching with KMnO4.
      RESULTS: The nuclear staining intensity of Feulgen stain was lower in the
      bleached sections, but this did not significantly affect the evaluation of
      ploidy. Heavy pigmentation caused some false peaks in the histograms (4 of 28
      measurements made on unbleached slides). CONCLUSION: Bleaching of sections with
      KMnO4 can be useful when heavy melanin pigmentation would make DNA measurements
      impossible or difficult in image analysis cytometry. Bleaching is not advisable
      when only lightly pigmented tumors are analyzed if nuclei obscured by any pigment
      granules are to be avoided. In large series containing both bleached and
      nonbleached specimens, statistical analysis of these groups should be separated.

PMID- 8534338
TI  - Flow and image cytometric DNA measurements in fine needle aspiration samples of
      prostatic neoplasms.
AB  - OBJECTIVE: To compare the DNA content measured by flow cytometry (FCM) and image
      analysis (IA) from prostatic fine needle aspiration (FNA) samples. STUDY DESIGN:
      A total of 48 samples were studied. FCM was performed on propidium iodide-stained
      nuclei according to the Vindelov method, and image analysis was performed on
      Feulgen-stained slides. Positive FNA results were grade (1-3) and compared with
      Gleason grades. RESULTS: Aneuploidy was closely related to positive FNA results
      (P < .01). DNA histograms were found to be aneuploid in all grade 3 carcinomas (n
      = 13) by IA and in 11 cases (84.6%) by FCM. Grade 2 carcinomas (n = 9) were found
      to be aneuploid with both methods. In grade 1 carcinomas (n = 10), 2 cases
      exhibited IA aneuploid profiles, whereas all FCM cases were diploid. Aneuploid
      profiles were more often associated with high Gleason scores than were diploid
      ones (P < .01). Among the 16 patients with negative FNA results, two cases had
      tetraploid DNA profiles related to contaminating seminal vesicle cells. The
      difference in DNA measurements reached 10.4% but was not statistically
      significant. CONCLUSION: These findings show that the two methods, as applied to
      prostatic FNA samples, give comparable results and that seminal vesicle cells may
      be responsible for false tetraploid profiles.

PMID- 8534339
TI  - Healthy aging and the quality of life.
AB  - The size of the elderly population, both in numbers and as a proportion of the
      whole, is increasing rapidly in most parts of the world. This trend, together
      with other deep changes in society, has made traditional ways of understanding
      and accommodating the aging process inadequate. Surveys suggest that economic
      security, psychosocial well-being, and a sense of being in reasonably good health
      are the most important values to aim for.

PMID- 8534340
TI  - Unfinished business: adult immunization against tetanus.
AB  - Where effective child immunization schemes have been established virtually all
      cases of tetanus occur in persons aged over 50 years. Adult immunization
      programmes should be introduced in order to protect this age group against the
      disease.

PMID- 8534341
TI  - The World Health Report 1995--bridging the gaps.
AB  - At the request of WHO's governing bodies, the first of a new series of annual
      reports was launched at the World Health Assembly in May 1995. The report is a
      self-contained, concise and analytical publication, which provides a review of
      the global health situation and needs and of problems faced by health systems, in
      order to recommend priorities for international health action and the
      Organization's activities in that context. The target readership is non-medical
      professionals such as policy-makers, planners for development, heads of donor
      agencies and other international funding institutions, financial experts and the
      educated public, as well as opinion-makers in the media and elsewhere. This
      article summarizes the first chapter of The World Health Report 1995--Bridging
      the gaps (1).

PMID- 8534342
TI  - The rise of international cooperation in health.

PMID- 8534343
TI  - Hippocrates: an ideal that lives.

PMID- 8534345
TI  - Reform of health care systems in eastern Europe.

PMID- 8534344
TI  - Monitoring birth defects: and seeking the causes.

PMID- 8534346
TI  - The future costs of hip fractures in Germany.

PMID- 8534347
TI  - Drug storage at home.

PMID- 8534348
TI  - Self-medication during pregnancy.

PMID- 8534349
TI  - Causes of maternal mortality in a semi-urban Nigerian setting.
AB  - Focus group discussions with people in Ekpoma, Nigeria, revealed them to be quite
      knowledgeable about haemorrhage in pregnancy and delivery. However, because of
      their inability to recognize early warning signs they continued traditional
      treatment even when clear evidence of danger existed. Furthermore, they tended
      not to seek help in clinics and hospitals because of sociocultural conditioning
      and a negative perception of the quality of care available. There were shortages
      of materials and adequately trained and committed personnel in the modern health
      institutions serving the community. An outline is given of the kinds of
      intervention needed in order to overcome these deficiencies.

PMID- 8534350
TI  - Training traditional birth attendants in Nigeria--the pictorial method.
AB  - High maternal mortality and morbidity rates are a challenge for all involved in
      the care of mothers and babies. One response takes the form of an educational
      programme led by professional midwives to teach traditional birth attendants to
      recognize risk conditions and improve their care of mothers and babies. Such a
      programme was organized as part of a Canadian-Nigerian safe motherhood
      initiative, and carried out in Akwa Ibom State, Nigeria.

PMID- 8534351
TI  - Training birth attendants in the Sahel.
AB  - A small-scale training programme for birth attendants in a remote area of Burkina
      Faso was evaluated two years after it had been started. The evaluation methods
      included interviews with trained birth attendants and the analysis of health
      service statistics and survey data. The findings showed that the programme had
      been moderately successful in imparting knowledge and overcoming cultural
      inhibitions about assisted deliveries. However, the effectiveness of the
      programme was severely curtailed by structural deficits in the health system,
      especially lack of skilled staff, supervision and transport. In deprived areas
      such as the Sahel, it is probably the health centre, the hospital and the
      referral system that should be the first priority for improvement, rather than
      grass-roots practices.

PMID- 8534352
TI  - Assessing health opportunities: a course on multisectoral planning.
AB  - Multisectoral planning can yield major benefits for health, especially in the
      case of water resource development projects. A two-week course, designed to
      involve mid-level officers from at least six government ministries in the
      planning and implementation of such projects, has been tested in Ghana, the
      United Republic of Tanzania, and Zimbabwe.

PMID- 8534353
TI  - Get to know your legislator.

PMID- 8534354
TI  - Current reality & future trends.

PMID- 8534355
TI  - The production of pharmaceutical proteins from the milk of transgenic animals.
AB  - The preparation of recombinant proteins of pharmaceutical interest from the milk
      of transgenic animals is becoming a reality. No protein has reached the market
      yet but several have been prepared in large quantities not only from laboratory
      animals but also from ruminants (goat and sheep) and pigs. Rabbit appears more
      and more to be an intermediate animal well adapted for the preparation of limited
      amounts of proteins. Several problems remain to be solved to optimize the method.
      The expression level of genes of interest associated with milk protein gene
      control regions is usually unpredictable. The recombinant proteins secreted in
      milk are not always in a satisfactory biochemical form. Cleavage and
      glycosylation are not always carried out correctly. The problem of the possible
      presence of agents pathogenic for humans in proteins extracted from milk is not
      completely solved. Prions have not been found in mammary glands and other milk
      pathogens may be controlled using good practice in breeding.

PMID- 8534356
TI  - Enzyme-linked immunosorbent assay for myosin heavy chains in the horse.
AB  - The content in slow and fast myosin heavy chains (MHC 1 and MHC 2) of 5 equine
      muscles was determined using an enzyme-linked immunosorbent assay. The results
      obtained with this immunoenzymatic method were compared with complementary
      techniques: electrophoresis and immunohistochemistry. Slices of masseter,
      diaphragm, tensor faciae latae, semitendinosus and cutaneus trunci were obtained
      from a 12-year-old saddle horse after slaughter. Muscular proteins were
      specifically extracted to be analysed by ELISA. The technique used 2
      complimentary monoclonal antibodies (MAb). MAb 1 was prepared from a human atrium
      specimen that reacted specifically against MHC 1. Mab 2 was prepared from myosin
      of rabbit psoas muscle and reacted against MHC 2. The masseter muscle contained
      solely MHC 1 (100%) and this was confirmed by electrophoresis and
      immunohistochemistry. By contrast, the cutaneus trunci was very poor in MHC 1
      (1.3%) and was entirely composed of MHC 2 (98.7%) which was confirmed by the
      other techniques. The diaphragm, tensor fasciae latae and semitendinosus
      contained 89, 40 and 2% of MHC 1, respectively. It was concluded that this ELISA
      method made it possible to measure a wide range of MHC contents in equine muscles
      with a good reproducibility. The results were consistent with those of the other
      fibre typing techniques. Moreover, this immunoenzymatic method is less time
      consuming than histological techniques and therefore offers new perspectives for
      muscle fibre typing in the horse.

PMID- 8534357
TI  - Two culture systems showing a biphasic effect on ovine embryo development from
      the 1-2 cell stage to hatched blastocysts.
AB  - This study compared the effect of using either CZB or TCM 199 media on both the
      development of 1-2 cell ovine embryos from superovulated ewes to the blastocyst
      stage (Experiment 1), and the hatching process of ovine blastocysts developed in
      vitro (Experiment 2). For the first 5 d, the CZB medium showed higher rates of
      embryo development than the TCM 199 medium (p < 0.001). The embryos reaching the
      > 16 cell stage were 79 vs 52% and 74 vs 20% with or without an oviductal
      monolayer, respectively, and those reaching the blastocyst stage were 71 vs 46%
      and 46 vs 13% with or without cells. The CZB medium was less able to support the
      hatching process of the blastocysts obtained in the first experiment than was the
      TCM-199 medium + 10% FCS (fetal calf serum) with cells (31 vs 92%; p < 0.001) or
      without cells (13 vs 66%; p < 0.001). No blastocysts completely escaped from the
      zona pellucida (ZP) in the CZB medium compared with 80 and 61% in the TCM 199
      medium with or without cells, respectively. In Experiment 3, 47% of the
      blastocysts migrated through the artificial opening of the ZP and hatched
      completely. After 24 h of culture in the CZB medium, however, they showed
      blastocoelic cavity breakdown. During the preliminary cleavages, the ovine
      embryos developed better in CZB medium than in TCM 199, but the latter was more
      efficient in promoting the hatching process of the blastocysts.

PMID- 8534358
TI  - Digestion of wheat gluten and potato protein by the preruminant calf:
      digestibility, amino acid composition and immunoreactive proteins in ileal
      digesta.
AB  - Three milk substitute diets, in which the protein was either provided exclusively
      by skim milk powder or partially (52%) substituted by a native wheat gluten or a
      potato protein concentrate, were given to intact or ileo-caecal cannulated
      preruminant calves. The apparent faecal nitrogen digestibility was lower (P <
      0.05) with the potato than with the gluten and control diets (0.90, 0.93 and
      0.95, respectively). The same trend was observed at the ileal level (0.83, 0.87
      and 0.91, respectively). Apparent digestibilities of most amino acids were lower
      with the potato than with the control diet (P < 0.05 for glutamic acid, proline,
      cystine, methionine, isoleucine, leucine, tyrosine and lysine). The same trend
      was observed with the gluten diet. Apparent digestibilities of glutamic acid and
      cystine were also lower (P < 0.05) with the potato than with the gluten diet.
      Protein fractions of Mr 43,000 and below 14,000 were detected immunochemically in
      ileal digesta corresponding to the potato diet, but no immunoreactivity was found
      in digesta with the gluten diet. However, the considerable enrichment of digesta
      in glutamic acid and proline with gluten indicates that dietary protein fractions
      rich in these 2 amino acids escaped digestion in the small intestine. With the
      potato diet, the undigested fractions contained high levels of aspartic acid,
      glutamic acid and cystine.

PMID- 8534359
TI  - Effects of 17 beta-estradiol on calcitonin and calcitonin-gene-related peptide
      secretions and contents in a murine medullary thyroid carcinoma C-cell line (CA
      77).
AB  - The effect of 17 beta-estradiol on calcitonin (CT) and calcitonin-gene-related
      peptide (CGRP) secretions in the murine CA-77 C cell line was studied after 1, 3,
      5 and 6 d of treatment. The release of both CT and CGRP significantly increased
      1, 3, 5 and 6 d after addition of 0.1 mumol/l estradiol alone to the culture
      medium. The C cell content of both peptides also increased after d of treatment
      with the same dose of estrogen. The enhanced CT and CGRP secretions induced by 17
      beta-estradiol were not inhibited by the simultaneous addition of 5 mumol/l of
      all-trans-retinoic acid. Dexamethasone alone increased the release of both
      peptides within 6 d. However, when cells were treated simultaneously with
      estradiol and 1 mumol/l dexamethasone, the addition of retinoic acid blunted both
      the CT and CGRP secretions induced by dexamethasone. These results showed that
      the positive effects of 17 beta-estradiol on both CT and CGRP secretions were
      modulated by dexamethasone and retinoic acid.

PMID- 8534360
TI  - Effects of gonadotrophin deprivation on follicular growth in gilts.
AB  - The endocrine and ovarian effects of hypophysectomy (n = 5) and gonadotrophin
      releasing hormone (GnRH) antagonist administration (Antarelix) (n = 5) were
      studied in gilts by comparison with control animals (n = 6). All gilts were given
      Regumate (20 mg/d for 18 d). The last day of Regumate was day 0. Hypophysectomy
      and initiation of Antarelix administration (0.6 mg iv twice daily for 7 d) were
      performed on day 5. All ovaries were obtained at slaughter on day 12. Blood
      samples were obtained daily from all Antarelix-treated and control sows to
      measure luteinizing hormone (LH) and follicle stimulating hormone (FSH)
      concentrations. Frequent sampling was performed on day 10 on control and
      Antarelix-treated gilts to assess pulsatile LH secretion. Oestrus or LH surge was
      initiated before the beginning of treatment in 2 hypophysectomized, 4 Antarelix
      treated, and 4 control females. Gonadotropins were undetectable in the blood of
      hypophysectomized sows on day 6. On day 10, pulsatile LH release was blocked in
      Antarelix-treated gilts. At no time were FSH concentrations significantly
      affected. Histological observation of the ovaries demonstrated that: (i) similar
      populations of healthy or total (healthy + atretic) follicles < 1 mm were found
      in the 3 groups of females; (ii) healthy follicles 1 to 2 mm in diameter were
      present in Antarelix-treated but not in hypophysectomized gilts; and (iii)
      healthy follicles > 2 mm were absent in Antarelix-treated and hypophysectomized
      gilts. The present study suggests the existence of 3 subgroups amongst antral
      follicles (gonadotropin independent: 0.19 to 1.1 mm; FSH dependent: 1.1 to 2 mm;
      LH pulses dependent: > 2 mm in diameter).

PMID- 8534361
TI  - Potential leukocyte attractants in the bovine peri-ovulatory ovary.
AB  - This study investigated interrelationships between the bovine ovarian cycle and
      white blood cells and tested the hypothesis that the ovary produces collagen-like
      materials with leukocyte attractant activity. We examined the in vitro secretion
      of leukocyte attractant activity by peri-ovulatory ovarian tissues and evaluated
      the leukocyte attractant potential of some ovarian biochemicals. Fluid from
      mature ovarian follicles and medium conditioned by follicular tissue, early
      luteal tissue or granulosa cells had significant attractant activity. The
      activity could be removed by protein precipitation but not by collagenase.
      Collagenase also failed to alter the electrophoretic profile of the samples.
      Collagenase (800 IU/ml), ascorbic acid (10-1,000 micrograms/ml) and CaCl2 (50-560
      micrograms/ml) had significant leukocyte attractant effects. Native collagen
      types I and IV (100-1,000 micrograms/ml) had fewer expressed attractant
      activities, which were unaffected by collagenase pre-treatment. The attractant
      activity of collagenase itself was removed by protein precipitation. Our
      observations suggest: (1) that follicular and luteal tissues produce leukocyte
      attractant(s); (2) that granulosa cells contribute to the secretion of this
      material; (3) that the principal ovarian attractants are neither the native
      collagen types I or IV nor their collagenase-releasable fragments; and (4) that
      collagenase, ascorbic acid and Ca2+ are strong candidates as attractant
      constituents of ovarian secretions.

PMID- 8534362
TI  - Microtubule rearrangement during in vitro maturation of pig oocytes. Effect of
      cycloheximide.
AB  - In freshly isolated fully grown pig oocytes at the germinal vesicle (GV) stage,
      the cytoplasmic microtubules are arranged in a meshwork. This microtubule
      arrangement is also maintained during the initial phases of meiotic maturation in
      vitro. A perinuclear array of microtubules is formed immediately before germinal
      vesicle breakdown (GVBD). Short-term treatment of oocytes with taxol when oocytes
      are at metaphase I stage induced formation of cytoplasmic asters. The oocyte
      cytoplasm is unable to respond to the taxol treatment at the earlier stages of
      meiotic maturation. In oocytes cultured with the proteosynthesis inhibitor
      cycloheximide, meiotic maturation is blocked. Condensation of chromatin occurs
      but the nuclear envelope is preserved and the microtubule arrangement is
      unchanged. A perinuclear array of microtubules does not appear and oocyte
      cytoplasm does not respond to short-term taxol treatment by the formation of
      cytoplasmic asters. We can conclude that the microtubule rearrangement and the
      acquisition of competence for tubulin assembly are blocked by cycloheximide and
      are thus dependent on de novo proteosynthesis.

PMID- 8534363
TI  - Behaviour of blastomere nuclei fused to mouse oocytes is affected by oocyte
      enucleation and age.
AB  - The influence of oocyte age and presence of oocyte meiotic apparatus on the
      behaviour of introduced blastomere nuclei was evaluated. Blastomeres from 4-cell
      mouse embryos were fused to intact (metaphase II) oocytes, demi-oocytes
      (nucleate) or cytoplast (anucleate). Fusion and simultaneous activation of the
      recipient oocytes were accomplished by a single electrical pulse at 20 or 24 h
      post human chorionic gonadotrophin (hCG) administration. The hybrids were fixed
      for evaluation 2 h after fusion. There was no difference in the behaviour of
      blastomere nuclei in whole oocytes and demi-oocytes. Most nuclei fused to the
      nucleate recipients at 20 h underwent breakdown of nuclear membrane (NMBD),
      chromosome condensation and consequently proceeded to telophase, in parallel with
      the resident meiotic chromosomes. Following fusion to cytoplasts, only a small
      portion of the blastomere nuclei underwent chromosome condensation and the vast
      majority (83%) of the nuclei remained in interphase. The influence of oocyte age
      on nuclear behaviour was assessed in oocyte-blastomere hybrids prepared by
      simultaneous fusion and activation at 20 and 24 h post-hCG administration. The
      introduced nuclei proceeded to telophase in 63% of the hybrids constructed at 20
      h, but in only 28% of those constructed at 24 h. We conclude that nuclei
      introduced into aged or enucleated oocytes at the time of activation are
      predominantly remodelled in their interphase configuration.

PMID- 8534364
TI  - Beneficial effect of oocyte activation prior to and during nuclear transfer in
      cattle using in vitro matured oocytes 24 h of age.
AB  - This research was designed to study in vitro development of bovine nuclear
      transferred embryos using enucleated young in vitro matured oocytes 24 h of age
      as recipient cytoplasts activated prior to nuclear transfer. The oocytes were
      enucleated and then activated with electric pulse at 24 h of age followed by
      incubation with cycloheximide for 6-7 h before nuclear transfer and membrane
      fusion with a blastomere of the 16-32 cell stage. This new protocol effectively
      improved cleavage (68 vs 17%, p < 0.05) and morula/blastocyst development of
      reconstructed embryos (29 vs 6%, p < 0.05), compared to similar nuclear transfer
      procedure without prior activation of recipient oocytes. Corresponding rates of
      cleavage and morula/blastocyst development for oocytes activated similarly
      without nuclear transfer were 49 and 19%. Factors affecting nuclear transfer were
      also compared. Two electric pulses for fusion increased rates of fusion (76 vs
      60%, p < 0.05) and subsequent development of cloned embryos (32 vs 11%, p <
      0.05). Cytochalasin B treatment following nuclear transfer manipulation seemed
      not to be beneficial in improving development of cloned embryos (p > 0.05). Both
      co-culture systems with buffalo rat liver (BRL) cells and cumulus cells promoted
      development of cloned embryos compared to the controls (28, 21 vs 0%, p < 0.05).
      The BRL cell system seemed to be better for manipulated embryos by reducing
      embryolysis.

PMID- 8534365
TI  - Cellular evaluation of bovine nuclear transfer embryos developed in vitro.
AB  - Cloned blastocysts developed in vitro for 7 d had a mean number of cells (82.86
      +/- 5.35) as evaluated by nuclei counting in serial optical sections using
      confocal microscopy, after staining with propidium iodide. This number was not
      significantly different from that of control IVF embryos cultured under the same
      conditions during the same period (mean = 88.89 +/- 7.53). Semi-thin sections
      revealed that most of the blastocysts had an inner cell mass (10/12) and a
      blastocoele. Under transmission electron microscopy, the trophectoderm appeared
      well differentiated as a polarized epithelium with apical microvilli and lateral
      junctions including desmosomes with bound intermediate filaments. The cytoplasm
      sometimes contained immature mitochondria or a large number of residual bodies.
      About half of the blastocysts examined had a large amount of cellular debris in
      the perivitelline space or inside the blastocoele cavity. The cloned blastocysts
      were also able to hatch in vitro by day 8 and SEM indicated a normal morphology
      of the trophectoderm cells with numerous apical microvilli. The high number of
      excluded or degenerating cells found in some embryos may partially explain early
      embryonic mortality that follows transfer. However, these observations do not
      give a clear explanation for the high incidence of fetal losses.

PMID- 8534366
TI  - Fibre type differentiation during postnatal development of miniature pig skeletal
      muscles.
AB  - Histochemical differentiation of 12 skeletal muscles with a different fibre type
      composition was studied in miniature pigs from 80 d of gestation to 1 year of
      age. Two fetal myofibre types were distinguished at 100 d of gestation by the
      mATPase reaction after acid preincubation. The staining for oxidative enzyme
      activities showed no conspicuous differences between fibres up to the 6th day
      after birth. Starting from this age it was possible to distinguish 3 fibre
      categories: SO (slow-twitch oxidative); FOG (fast-twitch oxidative-glycolytic);
      and FG (fast-twitch glycolytic). A characteristic cluster distribution of the 3
      fibre types was observed in all studied muscles with the exception of the
      masseter muscle which consisted only of the type SO and FOG fibres with a mosaic
      arrangement. The frequencies of both SO and FG fibre types increased and the
      proportion of type FOG fibres decreased during the postnatal period. These
      changes could be explained by developmental transformations among the individual
      fibre types. The type FOG fibres converted preferably to the fibre type (SO or
      FG) that prevailed in the muscles of adult animals.

PMID- 8534367
TI  - Alternative splicing generates four different forms of a non-transmembrane
      protein tyrosine phosphatase mRNA.
AB  - PTP-S is a widely expressed non-transmembrane protein tyrosine phosphatase
      (PTPase), which binds to DNA in vitro. The cellular PTP-S gene product is present
      mainly in the nucleus in association with chromatin. cDNAs related to PTP-S have
      been described from human and mouse cells. To establish the origin of molecular
      diversity in these cDNAs, genomic clones of rat PTP-S were isolated that span
      over 40 kb of the gene and contain 7 axons. The exon-intron splice sites in the
      catalytic domain are conserved between PTP-S and human PTP1B. Sequences specific
      to and homologous to human T-cell PTPase (TC-PTP) were found in the genomic
      clones of PTP-S, which are expressed in rat cells, as determined by using a
      specific probe and Northern blot analysis. Analysis of RNA from different rat
      tissues by reverse transcription-polymerase chain reaction (RT-PCR) showed the
      presence of four different forms of PTP-S mRNA (named PTP-S1, PTP-S2, PTP-S3, and
      PTP-S4). PTP-S1 is same as PTP-S reported previously by us. PTP-S2, which is the
      major form, differs from PTP-S1 in having additional 19 amino acids corresponding
      to exon E1. PTP-S4 is similar to human T-cell phosphatase. PTP-S3 differs from
      PTP-S4 in having a deletion of 19 amino acids corresponding to exon E1. Our
      results suggest that four different forms of PTP-S mRNA arise from a single gene
      by differential splicing. Two of these forms, PTP-S1 and PTP-S3, were not found
      in human cells, possibly due to the loss of an internal splice acceptor site in
      one of the exons, suggesting the occurrence of species-specific splicing in this
      gene.

PMID- 8534368
TI  - Molecular cloning and cell cycle-dependent expression of a novel gene that is
      homologous to cdc37.
AB  - A cDNA clone, termed N17, was isolated from a rat fibroblast 3Y1 cDNA library by
      a differential screening technique. The expression of the N17 gene was
      significantly increased in a variety of rapidly growing cells, including v-src-,
      v-Ha-ras-, or v-mos-transformed 3Y1 cells, when compared with parental 3Y1 cells.
      The N17 gene is present as a single copy in rat genome and is evolutionarily
      conserved among higher eukaryotes. The predicted open reading frame (ORF) encodes
      a polypeptide of 379 amino acids that exhibits a significant similarity with
      those of the cell cycle control protein Cdc37. The amount of N17 mRNA starts to
      be increased in the late G1 phase and the same level was retained until just
      before the G2/M phase. Taken together, these results suggest that N17 gene
      product may play a crucial role in the cell cycle control of 3Y1 cells.

PMID- 8534369
TI  - Nuclear factor binding to a DNA sequence element that represses MMTV
      transcription induces a structural transition and leads to the contact of single
      stranded binding proteins with DNA.
AB  - NRE1 is a DNA sequence element in the long terminal repeat of mouse mammary tumor
      virus through which viral transcription is repressed. In addition to double
      stranded DNA binding, both upper- and lower-stranded NRE1 binding activities
      occur in nuclear extracts. All three binding activities appear to be important
      for transcriptional effects. We report that occupancy of NRE1 within linear
      double-stranded NRE1 induces a structural transition in upstream flanking DNA
      that is facilitated by Mg2+. This transition was reflected by the striking DNase
      I sensitivity of the DNA. As Mg2+ concentration was increased, discrete DNase I
      hypersensitivity on one face of the DNA progressed to complete degradation of
      template. On the DNA face opposite the DNase I hypersensitivity, Mg2+ promoted
      regularly spaced cleavage by the single-strand-specific cleavage agents KMnO4 and
      S1 nuclease. Induction of degradation by DNase I occurred independently of MMTV
      sequences flanking NRE1, because nuclear extract-dependent DNase I sensitivity
      was conferred to an unrelated DNA fragment by introduction of a 23-bp NRE1
      containing oligonucleotide. UV protein-DNA cross-linking revealed that addition
      of Mg2+ to a double-stranded NRE1 DNA binding assay induced conversion from a
      double- to a single-stranded protein-DNA cross-linking pattern. Thus, nuclear
      factor binding to NRE1 induces changes in DNA topology that promote the direct
      contact of single-stranded NRE1 binding factors with DNA.

PMID- 8534370
TI  - Structure and expression of the bovine oxytocin receptor gene.
AB  - The gene for the bovine oxytocin receptor has been sequenced using a combination
      of clones derived from a bovine endometrial cDNA library from estrus and a bovine
      genomic DNA library, with confirmation of structure using reverse transcription
      PCR programmed by term myometrial RNA. The receptor belongs to the seven
      transmembrane domain family and predicts a protein of 391 amino acids. A
      comparison of the genomic sequence with the cDNA structure, as well as reverse
      transcription polymerase chain reaction (RT-PCR) analysis, shows there are two
      introns, one in the 5'noncoding region that appears to be differentially spliced
      in the bovine uterus and a conserved intron within the open reading frame between
      the regions encoding the transmembrane domains VI and VII. Northern blot analysis
      indicated three major transcripts in myometrium and endometrium in vivo at
      approximately 6.5 kb, 3.5 kb, and 2.0 kb. In situ hybridization analysis of
      uterine tissue at term showed highest mRNA concentrations in the endometrial
      epithelium, particularly in the deep glands, a pattern confirmed also at the
      immunohistochemical level by monoclonal antibodies raised against a human amino
      terminal peptide. Further confirmation of the identity of the receptor was
      obtained by transient transfection of a reconstituted receptor construct into COS
      7 cells. The expressed receptor was shown to have identical pharmacological
      properties in respect to various oxytocin analogs to the natural bovine
      endometrial receptor.

PMID- 8534371
TI  - Origin of replication of the Bacillus subtilis chromosome: in vitro approach to
      the isolation of early replicating segments.
AB  - We have developed a permeable cell system for the study of the molecular
      mechanisms involved in the control and initiation of DNA replication at the
      origin of the Bacillus subtilis chromosome. Our system take advantage of the
      synchronous initiation of DNA replication that occurs in outgrowing B. subtilis
      spores and the curtailment of DNA elongation by novobiocin. Early replicating DNA
      sequences were identified by the use of 5-mercury-dCTP as substrate, which allows
      the isolation of nascent DNA chains by affinity chromatography on thiol agarose.
      The average size of the isolated nascent DNA was 1,000 bp, and more than 80% of
      the nascent DNA chains had RNA primers at their 5' end. The study of the temporal
      order of chromosome replication near the origin using this experimental system
      showed that a segment containing recF and gyrB replicated earlier than a segment
      containing gyrA and part of the rRNA operon (rrnO). This observation is in
      agreement with previous in vivo data on the replication of origin region and
      supports the conclusion that the major activity in our in vitro system was the
      faithful replication of the ori region.

PMID- 8534372
TI  - A novel polymorphism in intron 6 of the human p53 gene: a possible association
      with cancer predisposition and susceptibility.
AB  - We present a novel polymorphic 8-bp sequence in intron 6 of the p53 gene that
      maps between bp 55 and 62 of the 3' end of exon 6. Of normal blood samples, 32%
      were heterozygotic for this polymorphism and display a NN' genotype, whereas 68%
      of the population is homozygotic for the N genotype. The rare homozygotic
      genotype N' was detected only in four blood samples of cancer patients.
      Peripheral blood of gastrointestinal (GI) and breast tumor patients demonstrated
      a higher incidence of heterozygosity (50%) than that of normal individuals.
      Analysis of the distribution of this polymorphism in tumor samples showed loss of
      heterozygosity (LOH). This LOH during tumor progression could exhibit preference
      to each one of the polymorphic alleles. The rare presentation of one allele and
      the increased incidence of heterozygosity in carcinoma patients may suggest an
      association between this polymorphism with cancer predisposition and
      susceptibility. The fact that genetic alterations occurring in noncoding regions
      may play a role in tumor development only further increases the extent of
      involvement of p53 in carcinogenesis.

PMID- 8534373
TI  - Transcription of the 5'-terminal cap nucleotide by RNA-dependent DNA polymerase:
      possible involvement in retroviral reverse transcription.
AB  - The possible transcription of the 5'-terminal cap nucleotide of mRNA by RNA
      dependent DNA polymerase was examined by a single-step assay, based on the
      generation of a hairpin structure during reverse transcription of globin mRNA.
      Using this approach, we demonstrated that the 5'-terminal cap nucleotide of mRNA
      is indeed transcribed by RNA-dependent DNA polymerase into a 3'-terminal residue
      of cDNA and were able to measure the extent of such transcription. The observed
      transcription of the cap nucleotide raises a number of questions that may be
      addressed using the relatively simple single-step assay employed in the present
      study. Cap nucleotide transcription by RNA-dependent DNA polymerase may have
      important implications for our understanding of the mechanism of action of
      reverse transcriptases. It may represent a selection mechanism for only partial
      transcription of the 5' repeat element of viral RNA genome, thus generating a RNA
      fragment that may play a role in priming of second (plus) DNA strand during
      retroviral reverse transcription. Moreover, the demonstrated ability of
      complementary nucleotides to form hydrogen bonds, even when in a parallel
      orientation, may have interesting and important consequences.

PMID- 8534374
TI  - Characterization of transgenic mice with an increased content of chromosomal
      protein HMG-14 in their chromatin.
AB  - Chromosomal protein HMG-14 is a ubiquitous nuclear protein that may modulate the
      chromatin structure of transcriptionally active genes. To gain insights into the
      cellular function of the HMG-14 protein, we generated two transgenic mouse lines
      carrying either two or six copies of the human HMG-14 gene. The transgenic mice
      express human HMG-14 mRNA and protein in all tissues examined at a level
      reflecting the increased gene dosage, suggesting that the HMG14 transgene
      contains all the control regions necessary for regulated gene expression.
      Expression of the human HMG-14 protein does not alter the expression of the
      endogenous mouse HMG-14 protein or its close homolog, protein HMG-17. The
      intracellular distribution of the exogenous human protein is indistinguishable
      from that of the endogenous mouse protein, resulting in a three-fold increase in
      the level of the chromatin-bound HMG-14. The transgenic mice had a higher
      incidence of epithelial cysts in their thymus than did control animals. We
      conclude that the cellular levels of HMG-14/-17 are determined by gene copy
      number, that the DNA fragment containing the gene and about 1,000 bp flanking its
      5' and 3' ends contain most of the elements necessary for gene expression, that
      the upper limits of HMG-14 in chromatin are not stringently regulated, and that a
      three-fold increase in chromatin-bound protein cause only mild phenotypic changes
      in the transgenic mice.

PMID- 8534375
TI  - Theory of dentin sensitivity.

PMID- 8534376
TI  - A desensitizing dentifrice with multiple oral health benefits formulated for
      daily use.

PMID- 8534377
TI  - Evaluation of a new dentifrice for the treatment of sensitive teeth.
AB  - A dentifrice containing 5% potassium nitrate, 1.3% soluble pyrophosphate, 1.5%
      polyvinylmethyl ether and maleic acid (PVM/MA) copolymer and 0.243% sodium
      fluoride in a silica base (Sensitive/Tartar Control) has been developed to
      concomitantly control tartar, caries and dentinal hypersensitivity. In vitro and
      animal studies show that the fluoride in this product effectively inhibits
      formation of enamel and dentine caries. In vitro studies also demonstrate that
      this dentifrice effectively reduces hydraulic conductance by occluding dentine
      tubules with a mixed surface deposit of copolymer and silica. Using an in vitro
      model that simulates in vivo conditions, this dentifrice also allows a rapid
      penetration of potassium nitrate through the dentine matrix. These findings
      demonstrate a correlation under in vivo conditions between the occlusion of
      dentine and the ability to deliver topically applied agents to target sites
      within or below dentine. The results indicate that this new dentifrice should
      provide multiple clinical therapeutic benefits including controlling tooth decay
      and tartar formation, and reducing and preventing dentinal hypersensitivity.

PMID- 8534379
TI  - Thermodontic stimulator--a new technology for assessment of thermal dentinal
      hypersensitivity.
AB  - A clinical investigation of the reproducibility of threshold and pain temperature
      scores obtained from use of the Thermodontic Stimulator (TDS) is reported. The
      TDS is designed for accurate clinical testing of thermal dentinal
      hypersensitivity. This instrument employs a variable stimulus/fixed response
      approach to clinical testing of thermal dentinal hypersensitivity. The TDS
      consists of a probe in a handpiece, a patient signaling device (joystick), a
      computer, and interface electronics. The TDS provides a precise means of
      assessing and recording the temperature which elicits a response to thermal
      stimulation from the subject being evaluated. Two temperatures are recorded. The
      threshold temperature is recorded when the patient is first able to sense that a
      cold stimulus has been applied to the tooth. The second score, pain temperature,
      is recorded when the subject first notices discomfort. Twenty-two subjects
      participated in this study. Results obtained from the 21 subjects who completed
      this study (one subject dropped out for non-compliance) demonstrated a
      reproducibility standard deviation of 1.1 degrees C for the threshold
      temperature, and 2.8 degrees C for the pain temperature for the duration of the
      study. There was a good degree of correlation between the measurements of any two
      test days (Pearson's correlation coefficient). There was no significant
      difference between the mean pain temperature scores of any two testing days.

PMID- 8534378
TI  - Fluoride and potassium availability in a new dentifrice that treats
      hypersensitivity and controls tartar.
AB  - The availability and stability of the active ingredients in a Sensitive/Tartar
      Control dentifrice have been evaluated in this study. The Sensitive/Tartar
      Control dentifrice contains 5% potassium nitrate as the anti-hypersensitivity
      agent, 0.243% sodium fluoride as the anti-caries agent, 2% tetrasodium
      pyrophosphate and 1.5% polyvinylmethyl ether/maleic acid (PVM/MA) copolymer as
      the antitartar system. The availability of potassium and fluoride from this
      dentifrice was tested and found to be acceptable in both freshly prepared and
      aged samples. Fluoride and potassium availability were also tested at dilutions
      similar to in vivo brushing levels, and the ability of the Sensitive/Tartar
      Control dentifrice to provide fluoride to enamel and reduce enamel solubility was
      measured. In these tests the Sensitive/Tartar Control dentifrice performed
      similarly to commercial fluoride dentifrices. Potassium availability was equal to
      Crest Sensitivity Protection, a product shown to be clinically effective against
      tooth sensitivity; fluoride availability and activity was shown to be equal to
      Crest Tartar Control, a product with published clinical anti-caries
      effectiveness.

PMID- 8534380
TI  - Efficacy of a dentifrice containing potassium nitrate, soluble pyrophosphate,
      PVM/MA copolymer, and sodium fluoride on dentinal hypersensitivity: a twelve-week
      clinical study.
AB  - The effect on dentinal hypersensitivity from the use of a dentifrice containing
      5.0% potassium nitrate, 1.3% soluble pyrophosphate, 1.5% PVM/MA copolymer, and
      0.243% sodium fluoride in a silica base over a twelve-week period was compared to
      a matching placebo dentifrice without potassium nitrate. A total of sixty-seven
      subjects were entered into the study, and stratified into two balanced groups
      according to their baseline mean thermal (threshold) temperature (Thermodontic
      Stimulator) and baseline mean tactile (Yeaple Probe) sensitivity scores. The two
      groups were randomly assigned to use either the potassium
      nitrate/copolymer/pyrophosphate dentifrice or the placebo dentifrice. The two
      groups were well balanced with regard to their mean baseline thermal and tactile
      sensitivity scores, sex and age. Subjects were instructed to brush their teeth
      twice daily (morning and evening) for one minute with their assigned dentifrice
      and a commercially available soft-bristled toothbrush. Dentinal hypersensitivity
      examinations, which included tactile sensitivity, threshold thermal sensitivity,
      pain thermal sensitivity, air blast, and a visual analog scale were conducted at
      baseline, six weeks, and twelve weeks. All examinations were conducted by the
      same dental examiner. After six weeks' use of their assigned products, those
      subjects in the potassium nitrate/copolymer/pyrophosphate dentifrice group
      demonstrated statistically significant improvements (p < 0.01), as compared to
      the placebo dentifrice, in the following parameters: 1) tactile; 2) thermal
      (threshold and pain); and 3) air blast. After twelve weeks' use of their assigned
      products, those subjects in the potassium nitrate/copolymer/pyrophosphate
      dentifrice group again demonstrated statistically significant improvements (p <
      0.01), in tactile, thermal (threshold and pain) and air blast sensitivity, as
      compared to the placebo dentifrice. It was concluded from this study that a
      dentifrice containing 5.0% potassium nitrate, 1.3% soluble pyrophosphate, 1.5%
      PVM/MA copolymer, and 0.243% sodium fluoride in a silica base is a clinically
      effective treatment for reducing dentinal hypersensitivity.

PMID- 8534381
TI  - Anticalculus efficacy of a dentifrice containing potassium nitrate, soluble
      pyrophosphate, PVM/MA copolymer, and sodium fluoride in a silica base: a twelve
      week clinical study.
AB  - A randomized, two-compartment calculus clinical study of twelve-weeks duration
      was conducted among a group of calculus-forming subjects in the St. Louis area.
      The purpose of this parallel and double-blind clinical study was to compare the
      effect of a dentifrice containing 5.0% potassium nitrate, 1.3% soluble
      pyrophosphate, 1.5% PVM/MA copolymer and 0.243% sodium fluoride in a silica base,
      to that of a placebo dentifrice, with regard to supragingival calculus formation.
      The study examiner, using the Volpe-Manhold Calculus Index, selected a panel of
      calculus-prone men and women who had completed a one-month placebo regimen. The
      Volpe-Manhold Calculus Index scores and the number of completely calculus-free
      sites were recorded. One-hundred and fifteen subjects were entered into the
      study. After an oral soft and hard tissue examination, the subjects were given a
      complete oral prophylaxis and randomly assigned to use either the placebo or test
      dentifrice for a 12-week home-use period. They were prohibited from using any
      other means of oral hygiene during the study. After completing 12 weeks of twice
      daily brushing at home using their assigned toothpaste and a standard soft
      bristled toothbrush, subjects were again assessed for supragingival calculus
      deposits and calculus-free sites. The dentifrice containing 5.0% potassium
      nitrate, 1.3% soluble pyrophosphate, 1.5% PVM/MA copolymer and 0.243% sodium
      fluoride in a silica base, inhibited supragingival calculus formation by 54.4%,
      as compared to a 0.243% sodium fluoride silica-based placebo dentifrice. The mean
      Volpe-Manhold Calculus Index scores were compared statistically and the
      difference indicated statistical significance at probability of 0.01 by means of
      an analysis of covariance (ANCOVA). The number of calculus-free sites, a second
      parameter of efficacy, also was compared and demonstrated an absolute difference
      of 32.6% in favor of the group using the dentifrice containing potassium nitrate,
      soluble pyrophosphate and PVM/MA copolymer compared to a placebo dentifrice
      (37.8% vs 5.2%, respectively). An analysis of covariance indicated that this
      improvement showed statistical significance at a probability of 0.01.

PMID- 8534382
TI  - Comparative efficacy of two dentifrices containing 5% potassium nitrate on
      dentinal sensitivity: a twelve-week clinical study.
AB  - The effect of a dentifrice containing 5.0% potassium nitrate, 1.3% soluble
      pyrophosphate, 1.5% PVM/MA copolymer, and 0.243% sodium fluoride in a silica base
      (Sensitive/Tartar Control) on dentinal hypersensitivity over a twelve-week period
      was compared to a commercially available dentifrice containing 5% potassium
      nitrate and 0.76% sodium monofluorophosphate in a dicalcium phosphate dihydrate
      base (Sensodyne-F). A total of ninety-seven subjects were entered into the study,
      and stratified into two balanced groups according to their baseline mean air
      sensitivity score and baseline mean tactile (Yeaple Probe) sensitivity score. The
      two groups were randomly assigned to use either the Sensitive/Tartar Control
      dentifrice or the commercially available hypersensitivity control dentifrice with
      potassium nitrate. The two groups were balanced with regard to their mean
      baseline air and tactile sensitivity scores, sex and age. Subjects were
      instructed to brush their teeth twice daily (morning and evening) for one minute
      with their assigned dentifrice and a commercially available soft-bristled
      toothbrush. Dentinal hypersensitivity examinations, which included tactile
      sensitivity, cold air blast, and a visual analog scale were conducted at
      baseline, six weeks, and twelve weeks. All examinations were conducted by the
      same dental examiner. After six weeks' use of the assigned dentifrices, there
      were no statistically significant differences between dentifrice groups in any of
      the parameters assessed (tactile, cold air blast and visual analog scale). After
      twelve weeks' use of the assigned products, there were no statistically
      significant differences between dentifrice groups in any of the parameters
      assessed (tactile, cold air blast and visual analog scale). Thus it can be
      concluded from this study that the use of a dentifrice containing 5.0% potassium
      nitrate, 1.3% soluble pyrophosphate, 1.5% PVM/MA copolymer, and 0.243% sodium
      fluoride in a silica base provides a clinically effective method of reducing
      dentinal hypersensitivity which is comparable in efficacy to a commercially
      available hypersensitivity control dentifrice containing 5% potassium nitrate and
      0.76% sodium monofluorophosphate in a dicalcium phosphate dihydrate base.

PMID- 8534384
TI  - Role of bacterial infection in exacerbation of multiple sclerosis.
AB  - One hundred consecutive patients admitted to the hospital with a diagnosis of
      exacerbation of multiple sclerosis were evaluated for an infectious process. All
      patients received a complete blood count, urinalysis, urine culture with
      susceptibility studies, blood cultures, and a chest x-ray at the time of
      admission. A control group of 55 patients carrying the diagnosis of multiple
      sclerosis but without symptoms of neurologic decline were also studied. Thirty
      five percent of patients experiencing exacerbation of their disease were
      identified as having a significant bacterial infection compared with 11% in the
      control group with quiescent disease. These results were significant with a P
      value of < 0.001. When presumptive viral and bacterial infections diagnosed
      before admission were included, almost 50% of patients could have had an
      exacerbation of their disease in response to an infectious process. Bacterial
      infection might well play a role in precipitating relapse in multiple sclerosis
      as well as influencing treatment.

PMID- 8534383
TI  - Outdoor winter activities of spinal cord-injured patients. With special reference
      to outdoor mobility.
AB  - Two hundred forty-seven patients with spinal cord injuries living in Hokkaido,
      the northern part of Japan, were mailed a questionnaire relating to winter
      outdoor activities. One hundred eight patients responded to the questionnaire, 98
      males and 10 females, with ages ranging from 30 to 79 (mean, 53.3) yr. Injury
      levels of patients were: cervical in 23 patients, thoracic and thoracolumbar in
      47, and lumbar in 38. All respondents were unable to walk independently because
      of quadriplegia or paraplegia. Approximately 90 percent of respondents found it
      necessary to go outside during the winter season. Eighty-five percent were
      outside during the coldest period. The most common reasons for outdoor activities
      were shopping and routine doctor's appointments. The main method of ambulating
      outside was a manual and/or electrically operated wheelchair, sometimes in
      conjunction with an automobile. However, there were many problems reported in
      using wheelchairs; for example, wheels and casters were very slippery on the snow
      and ice, casters were easily buried in the snow, and wheelchair rims were very
      cold to handle. It was also pointed out that exposure to cold weather induced
      physical problems such as muscle spasticity, pain, and numbness of lower
      extremities. This survey revealed that spinal cord-injured patients would benefit
      from a wheelchair specifically designed for winter conditions.

PMID- 8534385
TI  - Electromyographic motor Tinel's sign in ulnar mononeuropathies at the elbow.
AB  - A novel test for localizing ulnar mononeuropathies (UM), the electromyographic
      (EMG) motor Tinel's sign, has been developed. While recording with a monopolar
      needle from the abductor digiti minimi, the ulnar nerve is lightly rolled at
      multiple sites across the elbow, and the test is considered positive if a burst
      of EMG activity is observed simultaneously with nerve compression. To determine
      the use of the EMG Tinel's sign, we evaluated 70 control nerves and 50 clinically
      suspected UMs. The EMG Tinel's sign had a 78% sensitivity and a 79% specificity
      for suspected UM at the elbow. The clinical Tinel's sign was present in 68% of
      suspected UM cases, and the combined sensitivity of the EMG and clinical Tinel's
      sign was 96%. Using nerve conduction study (NCS) values derived from the control
      nerves, 62% of UM nerves had abnormal NCS/EMG findings, and 28% of UM nerves had
      NCS/EMG abnormalities that could be localized to the elbow. The development of
      motor axon mechanosensitivity at the site of nerve injury is a new finding, not
      previously observed in electrophysiologic studies of animal nerve injury models
      or reported in the electrodiagnostic literature.

PMID- 8534386
TI  - Electromyographic activity of the biceps brachii muscles and elbow flexion during
      associated reactions in hemiparetic patients.
AB  - Activity of the biceps brachii muscles and movements of the elbows were studied
      during associated reactions in hemiparetic patients and in healthy volunteers.
      Onset time and increase in electromyographic (EMG) activity during associated
      reactions and onset of elbow flexion and its maximal magnitude were measured.
      Testing was performed while standing with a footswitch attached to the sole of
      the nonparetic foot in patients and to the sole of the right foot in controls.
      Lifting of that foot generated a trigger signal that served to time the dependent
      variables. Bilateral EMG activity associated with one foot stance appeared in the
      two upper extremities in both patients and controls. Elbow flexion occurred in
      the majority of patients bilaterally, whereas in controls it frequently took
      place on one side only. There was a significant difference between patients and
      controls in onset of EMG activity and elbow flexion. This difference indicates an
      earlier preparatory activity to one foot stance in the upper limbs of patients
      than in healthy controls. The greatest excursion into flexion was measured in the
      paretic upper extremity of patients; it significantly exceeded both the flexion
      angle measured in controls and increase in flexion angle on the nonparetic side.
      Further understanding of the nature of associated reactions seems to be required
      for their adequate treatment by physical procedures.

PMID- 8534388
TI  - Interest in manual medicine among residents in physical medicine and
      rehabilitation. The need for increased instruction.
AB  - Manual medicine is an important part of the practice of physical medicine and
      rehabilitation (PM&R). Using a two-part questionnaire, we surveyed PM&R residents
      to determine their level of interest in manual medicine, their attitudes about
      this type of treatment, and the amount of formal training in manual medicine
      offered in PM&R residencies. Questionnaires were sent to all 75 PM&R residency
      training programs. Responses were received from 470 residents (41.6%) of 1126
      potential respondents; this represented 55 (73%) of the programs surveyed. Of the
      470 respondents, 363 (77.2%) believed that manual medicine should be a part of
      PM&R, 386 (82.1%) wanted more training in manual medicine, 389 (82.8%) believed
      that manual medicine is useful in the treatment of back/neck pain, and 392
      (83.4%) would refer patients for manual medicine treatment. However, only 124
      (27.3%) were receiving formal instruction in manual medicine during their PM&R
      residency training. Most of the 305 respondents who had received some exposure to
      manual medicine had done so through conferences (88.7%) and independent reading
      (66.9%). The results of this survey of PM&R residents demonstrate both a
      widespread interest in the use of manual medicine and an unmet desire for more
      instruction. Educational experiences in manual medicine should be provided so
      that, as residents become practicing physiatrists, they can either utilize this
      form of treatment or appropriately refer patients to other practitioners.

PMID- 8534387
TI  - ADL structure for stroke patients in Japan based on the functional independence
      measure.
AB  - The difficulty patterns of FIM (Functional Independence Measure) in Japan were
      determined and compared with patterns found in the United States to assess
      whether FIM can be used for worldwide comparisons of ADL (the activities of daily
      living). The FIM was measured for 190 stroke patients in several hospitals
      throughout Japan. The scores at admission and discharge were converted to an
      interval scale by Rasch analysis. Right and left brain lesion patients were
      analyzed separately. The FIM items were divided into two groups: motor items and
      cognitive items to minimize misfit. A degree of misfit was acceptable, except for
      bowel and bladder management, stairs, bathing, and expression. Motor items,
      eating, and bowel and bladder management were the easiest; stairs, bathing, and
      tub/shower transfers were the most difficult. The difficulty patterns of patients
      with left and right hemisphere lesions were almost identical. Bathing and
      tub/shower transfer were more difficult for Japanese patients than for those
      studied in the United States. Concerning the cognitive items, expression was
      easiest for patients with right hemisphere lesions but most difficult for those
      with left hemisphere lesions. Social interaction was easier for Japanese patients
      with left hemisphere lesions than the other patients. The item difficulty
      patterns in Japan differs slightly from those in the United States because of
      cultural differences. As countries show different patterns of difficulty, we must
      be careful when making international comparisons of FIM data converted by Rasch
      analysis.

PMID- 8534389
TI  - Incidence of dislocation following hip arthroplasty for patients in the
      rehabilitation setting.
AB  - Dislocation of a hip arthroplasty prosthesis is the most common serious
      complication after hip replacement. It is especially important in the
      rehabilitation setting because it is potentially preventable. The purpose of this
      study was to investigate differences in dislocation rates between rehabilitation
      and acute hospital settings. A retrospective chart review of total hip and
      bipolar hemiarthroplasty patients admitted to three rehabilitation hospitals was
      performed. Dislocation rates among 825 rehabilitation patients who met study
      eligibility criteria were compared with rates found among 5352 acute care
      patients reported in the published literature. The rate of hip dislocation among
      total hip replacement patients in rehabilitation hospitals was not significantly
      higher than that in acute settings (2.17% v 1.27%). Among bipolar
      hemiarthroplasty patients, however, the dislocation rate was markedly and
      significantly lower in rehabilitation than in acute settings (0% v 1.95%, P <
      0.01). Possible reasons for these results are discussed. Further research is
      needed to identify risk factors more precisely for prosthesis dislocation.

PMID- 8534390
TI  - Slip of the lip--tears of the superior glenoid labrum-anterior to posterior
      (SLAP) syndrome. A report of four cases.
AB  - The shoulder's unique wide range of motion is largely restrained by the articular
      capsule and the external ligaments of the glenohumeral joint. Internally, the
      long head of the biceps tendon passes within the capsule and inserts on the
      superior lip of the glenoid labrum. Trauma distracting this tendon can tear the
      superior glenoid labrum, producing the superior labrum anterior to posterior
      (SLAP) syndrome. Four patients, two of whom were female, presented with
      complaints of acute shoulder pain associated with weakness in abduction and
      forward flexion. Routine shoulder roentgenograms were normal. Magnetic resonance
      imaging (MRI) studies revealed a superior glenoid labral tear consistent with a
      SLAP syndrome. The superior labrum, unlike the firmly bound inferior portion, is
      loosely attached to the glenoid fossa. This inherent mobility predisposes it to
      disruption. To routine ultrasonography and arthrogram, the superior labrum may be
      obscured by superimposed structures. Shoulder arthroscopy, computed tomography,
      arthrography, and MRI have relatively equal sensitivity in visualizing these
      labral tears. The SLAP lesion accompanies 16% of all rotator cuff tears,
      occurring more often than heretofore recognized. When clinically suspected, they
      can be readily visualized by a noninvasive MRI examination.

PMID- 8534391
TI  - Graded exercise in three cases of heart rupture after acute myocardial
      infarction.
AB  - Despite advances in the study of exercise for acute myocardial infarction (AMI)
      patients, few studies on exercise for post-AMI heart rupture patients have been
      reported. We assessed three cases of heart rupture (of the left ventricular free
      wall in two cases and of the ventricular septum in one case) in post-AMI patients
      who underwent three-graded exercise. Two of the three patients were operated on,
      whereas one patient was managed conservatively for heart rupture. Two of the
      three cases had also suffered cerebral infarction post-AMI. The exercise program
      was composed of three grades, slow level walking (grade 1), mild reconditioning
      and activities of daily living (ADL) exercises (grade 2), and optional endurance
      training using machines below 75% of predicted maximal heart rate (grade 3).
      Electrocardiograms and blood pressure were monitored during all exercises. All
      patients had muscle weakness, poor endurance capacity, as well as low cardiac
      function (28-47% of left ventricular ejection fraction). Two patients underwent
      grades 1 and 2 exercise programs, and the other performed grades 1, 2, and 3
      exercise programs over a 3- to 10-wk period. We observed improvement in the
      double product, work capacity, and ADL without congestive heart failure, ischemic
      attack, or serious arrhythmias. However, the youngest patient, who underwent the
      grade 3 exercise program, died from a cardiac event 10 mo after onset of AMI. We
      conclude that post-AMI heart rupture patients should undergo delayed, gradual,
      low-level graded exercise (4-6 metabolic equivalents), with monitoring of blood
      pressure and electrocardiograms to improve work capacity, ADL, and the quality of
      life. However, daily activity and exercise intensity should be promptly
      supervised for those with severely deteriorated cardiac functions to prevent
      sudden cardiac event.

PMID- 8534392
TI  - Importance of paraspinal muscle electromyography in cervical and lumbosacral
      radiculopathies.

PMID- 8534393
TI  - Role of voluntarism and nongovernmental organizations in internationalizing
      rehabilitation medicine.

PMID- 8534394
TI  - The interdisciplinary team conference in rehabilitation medicine.

PMID- 8534395
TI  - The rehabilitation team.

PMID- 8534396
TI  - Reliability of a brief outpatient functional outcome assessment measure.
AB  - The stability of the musculoskeletal form of the Medical Rehabilitation Follow
      Along (MRFA) instrument was examined in 47 patients receiving outpatient
      rehabilitation services. The MRFA instrument was designed to provide information
      on quality of daily living, including physical function, pain, satisfaction, and
      emotional/psychological well-being. The instrument consists of thirty questions
      and can be administered as an interview or a written questionnaire. The MRFA
      instrument was developed using Rasch analysis procedures and is an extension of
      previous research involving the Functional Assessment Screening Questionnaire.
      Forty-seven patients completed the musculoskeletal form of the MRFA on two
      occasions separated by an interval of 1 to 7 days. The stability of responses was
      examined using the intraclass correlation coefficient (ICC) and kappa. ICC values
      for the sections of the MRFA instrument examining quality of daily living and
      physical functioning ranged from 0.74 to 0.97. ICC values for items assessing
      pain and feelings of well-being were more variable, ranging from 0.36 to 0.93.
      The kappa values displayed a similar pattern. The overall stability of the MRFA
      instrument was found to be adequate for gathering screening information in
      outpatient settings. Additional research is necessary to confirm the findings of
      this investigation and extend the results to a larger outpatient population.

PMID- 8534397
TI  - A long-term follow-up on "post-traumatic fibromyalgia" patients.

PMID- 8534398
TI  - Isolectins from seeds of Artocarpus lakoocha.
AB  - Two isolectins (ALA-I and ALA-II), were isolated from seed extracts of Artocarpus
      lakoocha by anion exchange chromatography on Q-Sepharose fast flow columns at pH
      8.5 and 8.0 ALA-I was unbound to the column at pH 8.5 and moved towards the
      cathode in non-denaturing polyacrylamide gel electrophoresis, whereas ALA-II
      possessed opposite properties. The two A. lakoocha agglutinins appeared to be
      composed of two dissimilar subunits (alpha and beta of M(r) 14,000 and 17,200)
      bound non-covalently. The isolectins possessed several similar properties
      including: blood type agglutination; pH optimum; pH and temp stability; as well
      as binding specificity towards asialomucins.

PMID- 8534399
TI  - NMR characterization of guanine DNA site alkylated by kapurimycin A3, an
      antitumour antibiotic from Streptomyces sp.
AB  - The kapurimycin A3-guanine adduct was formed by alkylation of the antitumour
      antibiotic with d(CGCG)2. The site of alkylation of the guanine was confirmed by
      comparative NMR studies with N-7-methyl-guanine in DMSO-d6.

PMID- 8534400
TI  - Anti-tumour-promoting glyceroglycolipids from the green alga, Chlorella vulgaris.
AB  - Two new monogalactosyl diacylglycerols were isolated from the freshwater green
      alga, Chlorella vulgaris, as anti-tumour promoters, together with three
      monogalactosyl diacylglycerols and two digalactosyl diacylglycerols. The new
      monogalactosyl diacylglycerol containing (7Z,10Z)-hexadecadienoic acid showed a
      more potent inhibitory effect toward tumour promotion than the other
      glycerolipids isolated.

PMID- 8534401
TI  - Composition and antimalarial activity in vitro of volatile components of Lippia
      multiflora.
AB  - The essential oil of Lippia multiflora was prepared by hydrodistillation of
      leaves and stalks and characterized by GC and mass spectroscopy. The oil was
      tested for antimalarial activity on in vitro cultures of Plasmodium falciparum
      (FcB1-Columbia chloroquine-resistant strain and F32-Tanzania chloroquine
      sensitive strain). The dilutions inhibiting the in vitro growth of the parasite
      by 50% 24 and 72 hr after administration of the essential oil to the parasite
      culture were 1/12,000 and 1/21,000, respectively. When tested on a highly
      synchronized culture, the essential oil inhibited growth mostly at the
      trophozoite-schizont step, indicating a potential effect on the first nuclear
      division of the parasite.

PMID- 8534402
TI  - Antibacterial phloroglucinols and flavonoids from Hypericum brasiliense.
AB  - Three known phloroglucinols (japonicine A, uliginosin A and isouliginosin B) and
      a new phloroglucinol (hyperbrasiol A) have been isolated from a petrol extract of
      the leaves and flowers of Hypericum brasiliense. Their structures were
      established by spectroscopic methods (UV, DCI-MS, 1H and 13CNMR, including
      SINEPT, HMBC, HSQC, DQFCOSY experiments). The substitution pattern of
      hyperbrasilol A was confirmed by X-ray crystallography. All four phloroglucinols
      were antibacterial against Bacillus subtilis in a TLC bioautographic assay. The
      flavonoids, kaempferol, luteolin, quercetin, quercitrin, isoquercitrin,
      hyperoside and guaijaverin, were isolated from a methanol extract of the same
      organs.

PMID- 8534403
TI  - Cyclopeptides from Stellaria yunnanensis.
AB  - In a previous paper, we reported the structural elucidation of stellarin A, a new
      cyclic heptapeptide, from the fresh roots of Stellarina yunnanensis Franch.
      Further chemical study on this plant led to the isolation of another two new
      cyclopeptides named stellarin B and C. Their structures were established to be
      cyclo(Gly-Ser-HOIle-Phe-Phe-Ala) and cyclo(Gly-Ser-HOIle-Phe-Phe-Ser),
      respectively, by spectral methods.

PMID- 8534404
TI  - Cytotoxic ent-kaurene diterpenoids from Isodon gesneroides.
AB  - From Isodon gesneroides, three new cytotoxic diterpenoids, gesneroidins A, B and
      C, together with one known diterpenoid, dawoensin A, were isolated, and the
      structure determination and unambiguous assignment of their stereochemistry and
      NMR spectral data were made by a combination of one-and two-dimensional NMR
      techniques, computer modelling calculations and X-ray analysis.

PMID- 8534405
TI  - De-O-ethylsalvonitin and salprionin, two further diterpenoids from Salvia
      prionitis.
AB  - From Salvia prionitis two new diterpenoids, de-O-ethylsalvonitin and salprionin,
      were isolated, and their structures and NMR data were assigned by spectral
      analysis and computer modelling calculations.

PMID- 8534406
TI  - Triterpenoid saponins from the aerial parts of Aster bellidiastrum.
AB  - Four major triterpenoid saponins were isolated from the aerial parts of Aster
      bellidiastrum. The structures were elucidated from their NMR and mass spectral
      data, and from derivatization. One is a new compound with the structure 3-O-beta
      D-glucopyranosyl-2 beta,3 beta,16 alpha,23-tetrahydroxyolean-12-en-28- oic acid
      28-O-beta-D-xylopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->2)-beta- D
      fucopyranoside, while the three others have been previously identified in
      extracts from various Bellis species.

PMID- 8534407
TI  - Dammarane saponins from Panax ginseng.
AB  - From the dried roots of Panax ginseng two new minor dammarane saponins named
      koryoginsenoside-R1 and -R2 were isolated, along with fourteen known saponins. On
      the basis of spectral and chemical evidence, the structure of the new saponins
      were elucidated as 6-O-[trans butenoyl-(1-->6)-beta-D-glucopyranosyl]-20-O-beta-D
      glucopyranosyl dammar-24-en-3 beta,6 alpha,12 beta,20(S)-tetrol and 3-O-[beta-D
      glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D- glucopyranosyl-(1-
      >6)-beta-D-glucopyranosyl] dammar-22-en-3 beta,12 beta, 20(S),- 25-tetrol,
      respectively.

PMID- 8534408
TI  - Linderniosides A and B, oleanane saponins from Lindernia pyxidaria.
AB  - Two new oleanane-type triterpene saponins, named linderniosides A and B, were
      isolated from the whole plants of Lindernia pyxidaria, together with a known
      triterpene glycoide, medicagenic acid 3-O-glucuronide. The structures of these
      compounds were determined on the basis of spectral and chemical evidence.

PMID- 8534409
TI  - Behavior problems of residents with dementia in special care units.
AB  - The prevalence and correlates of behavior problems were assessed among 614
      residents with dementia living in 70 special care units (SCUs) throughout the
      country. We assessed behavior problems at admission, using a comprehensive
      measure of behavior problems, the Memory and Behavior Problems Checklist-Nursing
      Home version. Overall, behavior problems were quite prevalent, with some problems
      reported for > 90% of the sample. Emotional distress was a frequent area of
      concern, second only to memory-related problems. Although the overall number of
      behavior problems was not associated with cognitive impairment, age, or gender,
      item analyses revealed relationships between these variables and individual
      behavior problems. The applicability of these findings to the care of the SCU
      resident is discussed.

PMID- 8534410
TI  - Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF
      neurotransmitters and neuropeptides.
AB  - Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer
      disease (AD) therapy. ALCAR seems to exert a number of central nervous system
      (CNS)-related effects, even though a clear pharmacological action that could
      explain clinical results in AD has not been identified yet. The aim of this study
      was to determine cerebrospinal fluid (CSF) and plasma biological correlates of
      ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment.
      Results show that ALCAR CSF levels achieved under treatment were significantly
      higher than the ones at baseline, reflecting a good penetration through the blood
      brain barrier and thus a direct CNS challenge. ALCAR treatment produced no
      apparent change on CSF classic neurotransmitters and their metabolite levels
      (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among
      CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic
      hormone remained unchanged, beta-endorphins significantly decreased after
      treatment; plasma cortisol levels matched this reduction. Since both CSF beta
      endorphins and plasma cortisol decreased, one possible explanation is that ALCAR
      reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis
      hyperactivity. At present, no clear explanation can be proposed for the specific
      mechanism of this action.

PMID- 8534411
TI  - Reality orientation therapy in Alzheimer disease: useful or not? A controlled
      study.
AB  - The aim of this controlled study was to evaluate the effects of a long-term
      program of formal didactic group therapy [class reality orientation therapy
      (ROT)] in Alzheimer disease. The study was conducted in the day hospital of an
      Alzheimer Dementia Research and Care Unit (Brescia, Italy), a multidisciplinary
      care center providing diagnostic evaluation and treatment for elderly patients
      with cognitive impairment. The criteria for the inclusion of patients in the
      study were mild to moderate cognitive impairment [Mini Mental Status Examination
      (MMSE) between 11 and 24/30] and absence of major aphasia, blindness, and overt
      behavioral disturbances such as wandering or agitation. Sixteen patients
      constituted the experimental group and 12 the control group. The last cognitive,
      functional, and affective evaluation in the experimental and control group was
      performed 8.2 and 8.5 months after baseline assessment, respectively. The
      experimental group had repeated cycles of 1-month ROT classes, and 5-7 weeks was
      allowed between each cycle. Differential change for MMSE score between the two
      groups was significant. In the experimental group, there was mild improvement in
      MMSE score (0.68 point) at the last assessment, whereas the control group
      declined (-2.58 points). This treatment effect on MMSE score (3.27 points) was
      controlled for potential confounders in a multiple regression analysis. Adjusted
      treatment effect, including age, education, baseline MMSE, disease duration,
      disease severity, number of diseases other than Alzheimer, and time elapsing from
      baseline to last assessment, was very slightly lower: 3.12. In the experimental
      group, treatment effect was evaluated by comparing ROT cycle changes and resting
      period changes. A clearly significant treatment effect was found for MMSE and
      verbal fluency.

PMID- 8534412
TI  - The target population in phase I clinical trials of cholinergic compounds in
      Alzheimer disease: the role of the "bridging study".
AB  - Our experience with studies investigating central nervous system active compounds
      in Alzheimer disease (AD) patients suggest that conducting a "bridging study," in
      which patients from the target population are included in Phase I, could expedite
      the drug development process in AD. With one acetylcholinesterase (AChE)
      inhibitor compound (velnacrine), we found that AD patients tolerated considerably
      lower dosages than young normals and healthy elderly subjects, whereas our
      findings were exactly the opposite with another AChE inhibitor (eptastigmine). In
      studies of a muscarinic agonist (CI-979), AD patients were able to tolerate
      dosages higher than those that were well tolerated in young normals. A possible
      explanation for differences in drug effect and tolerance in the target population
      may be the pathologic changes in both the brain and the peripheral nervous system
      that are associated with AD.

PMID- 8534413
TI  - Evaluation of 100 patients with dementia in Sao Paulo, Brazil: correlation with
      socioeconomic status and education.
AB  - One hundred consecutive outpatients with dementia were prospectively studied to
      investigate the diagnoses of dementing diseases and to correlate these diagnoses
      with socioeconomic status and with education. Alzheimer disease was the most
      common cause of dementia (54%), followed by vascular dementia (20%). Eight
      patients presented with potentially reversible causes of dementia. These
      frequencies are similar to those reported by case register studies from Western
      Europe and the United States. We did not find differences in the frequencies of
      the dementing diseases according to socioeconomic status or education. Alzheimer
      disease was the most common cause of dementia in all socioeconomic classes.
      Potentially reversible dementias, vascular dementias, and other secondary
      dementias were not more frequent in the lower socioeconomic strata. There was a
      trend to a higher frequency of vascular dementia among patients with less
      education, but this was not statistically significant.

PMID- 8534414
TI  - Validation of the NINCDS-ADRDA criteria regarding gait in the clinical diagnosis
      of Alzheimer disease. A clinicopathologic study.
AB  - The NINCDS-ADRDA criteria for the clinical diagnosis of probable Alzheimer
      disease (AD) state that "gait disturbances at the onset or very early in the
      course of the illness make the diagnosis of Alzheimer disease uncertain or
      unlikely," yet there have been few studies documenting the validity of the
      statement. We therefore reviewed all cases of pure autopsy-proven AD in the
      Ramsey Brain Bank to determine how frequently an abnormal gait was noted at time
      of presentation. Any reported gait disturbance was considered an abnormal gait.
      Only cases for which medical records were available documenting the patient's
      presentation for dementia were included. Cases were excluded if any other
      pathology was present that may have contributed to the patient's dementia or to a
      gait disorder, if neuroleptic medication had been used, or if there was a
      preexisting gait disorder. Clinical dementia severity at time of presentation was
      graded as mild, moderate, or severe per DSM-IIIR criteria. Of the 95 cases that
      met study criteria, none of the 36 patients with mild dementia were reported to
      have had an abnormal gait. Sixteen percent of the patients with moderate and 32%
      with severe dementia had gait abnormalities reported. This study confirms the
      statement regarding gait in the NINCDS-ADRDA criteria.

PMID- 8534415
TI  - Apolipoprotein epsilon 4 allele in Swedish twins and siblings with Alzheimer
      disease.
AB  - Allelic frequencies of apolipoprotein epsilon 4 were compared in 13 dizygotic
      twin pairs and 13 sibling pairs in which at least one member has Alzheimer
      disease (AD). Among discordant pairs of twins and siblings, frequencies were
      significantly greater in affected than intact partners. There was no significant
      difference in allelic frequencies between twins with a positive family history
      and twins with a negative family history. The epsilon 4 allele was more common in
      the sibling sample selected for family aggregation of AD than the twin sample.
      Several lines of evidence indicate that while the epsilon 4 allele appears to be
      one risk factor for AD, other etiological factors must be considered as well.

PMID- 8534416
TI  - Early symptoms and neurological findings in demented subjects from a community
      survey.
AB  - The prevalence of the symptoms at disease onset reported by close informants, in
      an unselected group of demented elderly, is presented in this study. Of the 174
      dementia cases, 98 were Alzheimer disease (AD), 41 were vascular dementia (VaD),
      and 35 were other dementias. In 42% of AD subjects, single memory deficit was the
      earliest problem, while in 56% of VaD cases, the tendency was to present two or
      more disturbances in the early stages. Slightly younger mean age at onset was
      reported in VaD than in AD cases. Our results support the hypothesis that the
      debut of the dementia is variable with any combination of symptoms. However, when
      memory problems start, assessment is needed. Among the neurological findings in
      the clinical examination, extrapyramidal signs were present in 25% of all
      dementia cases and in 20% of AD cases. A higher frequency of extrapyramidal signs
      was present in more severe cases, confirming previous reports of the unfavorable
      prognostic value of these signs.

PMID- 8534417
TI  - Cholinergic signaling in Alzheimer disease: therapeutic strategies.

PMID- 8534418
TI  - Signal transduction mechanisms in Alzheimer disease.
AB  - The present article focuses on our studies on the metabolism of the inositol
      phospholipids in Alzheimer disease (AD). The phospholipase C (PLC) isozyme, PLC
      delta 1, was abnormally accumulated in neurofibrillary tangles (NFT), the
      neurites surrounding senile plaque cores, and neuropil threads in AD brains. Anti
      PLC-delta 1 antibody marked the same NFT-bearing neurons containing tau
      immunoreactivity. Electron microscopic immunocytochemistry revealed that
      antigenic determinants unique to PLC-delta 1 are mainly present intraneuronally
      on the amorphous granular components of NFT as well as the abnormal filaments.
      Although the concentration of PLC-delta 1 protein was significantly higher in the
      cytosolic fraction of AD cortical tissue than in control brains, the specific
      activity of PLC-delta 1 is decreased in AD brains. The amounts of PLC-beta 1 and 
      gamma 1 and type beta protein kinase C were significantly reduced in the
      membranous fraction of the AD temporal cortical tissues compared with controls.
      The PLC-delta 1 abnormality was also present in nonneuronal tissues as well as
      the brains of patients with AD. It was revealed that nitric oxide (NO) formation
      secondary to Ca2+ influx by N-methyl-D-aspartate (NMDA) receptor activation leads
      to modifications of PLC-delta 1 similar to those seen in AD brains. These results
      suggest that altered Ca2+ homeostasis, occurring as a consequence of aberrant
      phosphoinositide metabolism, may be related to key features of AD such as
      neurofibrillary degeneration, aberrant amyloid deposits, and neuronal death.

PMID- 8534419
TI  - Cholinesterases and the pathology of Alzheimer disease.
AB  - Alzheimer disease (AD) is accompanied by a marked loss of acetylcholinesterase
      (AChE) activity associated with cortical cholinergic axons and cholinoceptive
      neurons. Simultaneous with this loss, cholinesterase (ChE) activity emerges in AD
      cortex in the form of AChE and butyrylcholinesterase activity associated with
      plaques, tangles, and amyloid angiopathy. Our observations have shown that the
      ChEs associated with the pathological lesions of AD (ADChEs) possess different
      enzymatic properties and quite possibly are of a different source as compared
      with the ChEs associated with normal neurons and axons. The ADChEs most likely
      have noncholinergic functions involved in the pathogenesis of AD. The postulated
      functions include acting as proteases/peptidases, participating directly in the
      amyloidogenic processing of the amyloid precursor protein, and causing aberrant
      growth of neuronal processes. The therapeutic and diagnostic implications of
      ADChEs are discussed.

PMID- 8534420
TI  - Nonclassical roles of cholinesterases in the embryonic brain and possible links
      to Alzheimer disease.
AB  - Evidence about nonclassic functions of acetyl- (AChE) and butyryl-cholinesterase
      (BChE) during embryonic development of vertebrate brains is compared with
      evidence of their expression in Alzheimer disease (AD). Before axons extend in
      the early neural tube, BChE expression shortly precedes the expression of AChE.
      BChE is associated with neuronal and glial cell proliferation, and it may also
      regulate AChE. AChE is suggested to guide and stabilize growing axons.
      Pathologically, cholinesterase expression in AD shows some resemblance to that in
      the embryo. These findings are inconsistent with the "cholinergic hypothesis."
      Rather, it is suggested that cholinesterases in AD function nonclassically as in
      the embryo, possibly as part of a "neoembryonic" restorative program. These views
      may open new strategies for pharmacology and therapy for AD.

PMID- 8534421
TI  - Nicotinic receptors and neurodegenerative dementing diseases: basic research and
      clinical implications.
AB  - Nicotinic cholinergic agonists represent a relatively newly developing area for
      therapeutic intervention in Alzheimer disease (AD) and related neurodegenerative
      dementias. Loss of cholinergic receptors has been reported not only in AD but
      also in Parkinson's disease, Lewy body dementia, and progressive supranuclear
      palsy. Clinical studies suggest that compounds that act to stimulate nicotinic
      receptors may improve learning and memory in a variety of models of cognitive
      impairment in animals. Early clinical studies have suggested positive effects on
      cognition of nicotine in human beings with and without AD. Finally, nicotinic
      compounds might show the progression of AD, as suggested by preclinical models of
      cell death as well as epidemiological evidence of a protective effect of smoking
      in AD and Parkinson's disease.

PMID- 8534422
TI  - Clinical heterogeneity: responders to cholinergic therapy.
AB  - Clinical Alzheimer disease (AD) is a heterogeneous disorder, and it is possible
      to subgroup patients by a number of different criteria. One such subgrouping is
      those who have a positive response to cholinergic therapy and those who do not.
      This phenomenon has been clearly recognised in a number of therapeutic trials of
      cholinesterase inhibitors and is likely to be an issue in clinical practice.
      Tacrine, the first cholinesterase inhibitor to be approved for the treatment of
      AD, has, at best, modest effects on 20-50% of patients and is associated with a
      high frequency of side effects, including liver transaminitis. The potential of
      clinical tests or other investigations to identify those patients who are more
      likely to respond to cholinergic therapy would be a valuable aid in the clinical
      use of these therapies. In this article we review the issue of heterogeneity in
      patient populations, in the design of trials and in the pharmacological compounds
      used in trials. We then summarise the findings of a number of small studies of
      potential response predictors, which include the use of psychometric tests,
      orthostatic blood pressure, pupillary dilation, the electroencephalogram,
      cerebrospinal fluid neurochemistry, and techniques involving functional imaging.
      Although some results are promising, generalisability is limited by the small
      numbers of patients studied and the frequent open nature of the designs used. The
      main conclusion that can be drawn is that adequate doses are required to achieve
      therapeutic plasma levels before nonresponse is accepted.

PMID- 8534423
TI  - Alzheimer disease, attention, and the cholinergic system.
AB  - Recent neuropsychological studies suggest that, in addition to prominent mnemonic
      dysfunction, attentional impairments are a core feature of Alzheimer disease
      (AD). As is the case for memory, attention is not a unitary process, and only
      certain components of attention are disrupted in mild AD, particularly sustained
      and spatial attention. In this article we review evidence from both human and
      nonhuman neuropsychopharmacology that leads us to suggest that (at least some of)
      the attentional impairments seen in AD can be related to damage to the basal
      forebrain cholinergic system (BFCS), in particular the nucleus basalis of Meynert
      (nbM), which undergoes significant neuronal loss in AD. The BFCS provides the
      major cholinergic innervation to the cortex and innervates brain regions such as
      the thalamus, prefrontal cortex, and parietal lobes known to be involved in
      attentional operations. In addition, studies conducted by our group suggest that
      drugs acting to stimulate the cholinergic system, in particular tacrine and
      nicotine, can significantly improve attentional function in patients with AD as
      measured by improved performance on objective computerised cognitive tasks.
      Furthermore, cholinergic drugs may also have some utility in other disorders with
      attentional pathology, such as Parkinson's disease.

PMID- 8534425
TI  - Distribution of nicotinic subtypes in human brain.
AB  - The distribution of high-affinity nicotine and alpha-bungarotoxin receptors has
      been compared in a number of human brain areas and related to the available data
      on receptor subtype mRNA expression. Nicotine binding is high in the thalamus,
      striatum, and substantia nigra pars compacta, and although not generally high in
      the hippocampal formation, it is concentrated in the entorhinal cortex, the
      subicular complex, and the stratum lacunosum moleculare. Nicotine binding is
      relatively low in the cerebral cortex, but it demonstrates varied patterns of
      distribution in different areas. Nicotine binding is also present in the
      cerebellar cortex and dentate nucleus. Nicotine binding in the thalamus
      corresponds to alpha 3 expression, but at variance to data from rodents, there is
      little evidence of beta 2 mRNA in this brain area. By contrast, there is beta 2
      mRNA but not alpha 3 mRNA in the striatum. In the hippocampal formation both
      alpha 3 and beta 2 mRNAs are expressed, but the pattern of distribution does not
      resemble nicotine binding, only reaching moderate levels in the dentate granule
      cell layer and in the CA3 region. In the neocortex, alpha 4 expression is more
      widely distributed than alpha 3, but both are associated with pyramidal neurons.
      The distribution of nicotine binding, concentrated in brain areas gating
      multimodal inputs and often uncorrelated with cholinergic innervation, suggests a
      neuromodulatory role, possibly facilitating glutamatergic transmission. The
      distribution of alpha-bungarotoxin binding is different from that of nicotine in
      the hippocampal formation, being highest in the CA1 region and the dentate
      granule cell layer, but similar to nicotine binding in the substantia nigra pars
      compacta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534424
TI  - Potential treatment of Alzheimer disease using cholinergic channel activators
      (ChCAs) with cognitive enhancement, anxiolytic-like, and cytoprotective
      properties.
AB  - Compounds that activate neuronal nicotinic acetylcholine receptors (nAChRs) may
      have potential benefit in the treatment of dementia, especially Alzheimer disease
      (AD). This article summarizes the preclinical pharmacology of ABT-418 [(S)-3
      methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole], a novel analog of (-)-nicotine
      that is being clinically evaluated for the treatment of AD. ABT-418 is a
      cholinergic channel activator (ChCA) with cognitive enhancement and anxiolytic
      like activity possessing a substantially reduced side-effect profile compared to
      (-)-nicotine [Arneric SP, Sullivan JP, Briggs CA, et al. (S)-3-Methyl-5-(1-Methyl
      2-Pyrrolidinyl)Isoxazole (ABT-418): A novel cholinergic ligand with cognition
      enhancing and anxiolytic activity. I. In vitro activity. J Pharmacol Exp Ther
      1994 ;270:310-318; Decker MW, Brioni JD, Sullivan JP, et al. (S)-3-Methyl-5-( 1
      Methyl-2-Pyrrolidinyl)Isoxazole (ABT-418): A novel cholinergic ligand with
      cognition-enhancing and anxiolytic activities: II. In vivo characterization. J
      Pharmacol Exp Ther 1994a;270:319-328; Decker MW, Curzon P, B rioni JD, Arne ric
      SP. Effects of ABT-418, a novel cholinergic channel ligand, on place learning in
      septal-lesioned rats. Eur J Pharmacol 1994;261:217-222; Garvey DS, Wasicak JT,
      Decker MW, et al. Novel isoxazoles which interact with brain cholinergic channel
      receptors have intrinsic cognitive enhancing and anxiolytic activities. J Med
      Chem 1994;37:1055-1059]. ABT-418 may be the first agonist of nAChRs to be
      developed and evaluated specifically for the treatment of AD. Some brief
      speculation will be given on the potential benefits that this or other ChCAs may
      have in treating neurodegenerative disorders as compared with (-)-nicotine, and
      how this differs from other potential treatment approaches.

PMID- 8534426
TI  - Serodiagnosis of Helicobacter pylori infection in patients with human
      immunodeficiency virus infection.
AB  - In contrast to the established role of Helicobacter pylori gastritis in gastritis
      and duodenal ulcer in general, conflicting results have been reported in patients
      with human immunodeficiency virus (HIV) infection and the acquired
      immunodeficiency syndrome. The seroprevalence during early HIV infection is
      unknown. We retrospectively studied 102 patients with HIV infection early during
      the infection and in most cases in asymptomatic patients. Serological IgG
      antibody response to H. pylori was assessed by ELISA. Compared with an age
      matched control group the seroprevalence of H. pylori positivity was not
      significantly different (19% vs 25%). We observed no association with CD4 counts,
      p24 antigen, antibiotic prophylaxis with sulfamethoxazole/trimethoprim or
      antiretroviral treatment. In 54 of 83 patients initially seronegative a second
      examination was performed after a median of 24 months (range 3-60 months) and 2
      patients had H. pylori seroconverted, indicating an incidence of new infection of
      2%/year. In conclusion, previous reports have underestimated the prevalence of H.
      pylori infection in HIV patients, which seems to be similar to that in an HIV
      negative population.

PMID- 8534427
TI  - Occurrence of human papillomavirus infection in cervical intraepithelial
      neoplasia. A retrospective histopathological study of 317 cases treated by laser
      conization.
AB  - The aim of the study was to compare the histological outcome of the cone
      specimens with the diagnoses of the preoperative biopsies, to assess the
      distribution of histological features consistent with human papillomavirus (HPV)
      infection and, finally, to analyse the impact of cellular HPV features on
      classification of cervical intraepithelial neoplasia (CIN). The study comprised a
      population of 317 women treated for CIN by laser conization during the period
      1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their
      corresponding cones) were studied retrospectively for CIN classification and
      examined for morphological signs of HPV infection. For presentation of the
      results, we used a modified terminology for CIN. Low-grade (LG) CIN included
      borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN
      III. The blinded histopathological review revealed HG CIN both in the
      preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions
      were found in the preoperative biopsies and their corresponding cone specimens in
      6% of the study population. HPV features were present in 65% of the preoperative
      biopsies, and were most prevalent in women under 29 years of age (p < 0.001).
      Thirteen percent of the total biopsy material was downgraded. The downgrading was
      most prevalent among original CIN II (p = 0.009) and HPV-negative biopsies (p <
      0.001). This study demonstrates that CIN lesions are frequently associated with
      HPV features, which are significantly more prevalent in the youngest women.
      Concomitant HPV features do not influence the CIN classification.

PMID- 8534428
TI  - Intracellular and surface distribution of CD9 in human eosinophils.
AB  - Expression of CD9 is a feature of both eosinophils and platelets. We have
      investigated the CD9 expression on resting and activated eosinophils with regard
      to possibly interacting platelets. Mixed leukocytes were obtained from the
      platelet-containing (PC) and platelet-depleted (PD) peripheral blood of healthy
      donors. A cell membrane permeabilization technique, the FOG method, enabled us to
      detect the eosinophils as a separate population and permitted flow cytometric
      analysis of both surface and intracellular antigens. Monoclonal antibodies
      against CD61 were used to identify platelets. The CD9/CD61 ratio indicated that
      CD9 on resting eosinophils originates mainly from eosinophils and not from
      adhered platelets. No difference in CD9 expression was obtained between resting
      eosinophils in PC and PD blood. However, the expression of CD9 was decreased (p <
      0.05) on eosinophils in PMA-activated PD blood but increased (p = 0.001) in PC
      blood, probably due to interacting platelets since CD61 increased simultaneously.
      In addition, we were able to detect an intracellularly stored pool of CD9 in
      eosinophils which decreased after activation with PMA. Together these results
      indicate a translocation of intracellularly stored CD9 to the cell membrane upon
      activation, probably followed by a subsequent shedding.

PMID- 8534429
TI  - Relationship between the cell surface hydrophobicity and adherence of Candida
      krusei and Candida albicans to epithelial and denture acrylic surfaces.
AB  - C. krusei is an emerging pathogen, especially in immunocompromised hosts, and is
      implicated, together with Candida albicans, as an etiological agent of oral
      candidoses. As the cell surface hydrophobicity of these yeasts appears to be
      important in the pathogenesis of superficial candidoses, 20 oral isolates of C.
      krusei and 5 oral isolates of C. albicans were investigated using a biphasic
      (hydrocarbon/aqueous) separation hydrophobicity assay. All the C. krusei isolates
      demonstrated significantly greater hydrophobicity than the C. albicans isolates
      (p < 0.001). Further, there were significant intraspecies differences in cell
      surface hydrophobicity amongst C. krusei isolates. When hydrophobicity and
      adhesion to surfaces were compared using data from a previous study, there was a
      positive correlation between the cell surface hydrophobicity and adhesion of C.
      krusei isolates to HeLa surfaces (r = 0.53, p < 0.05), but not to acrylic
      surfaces. The current data, while confirming the inter- and intraspecies
      differences in cell surface hydrophobicity of Candida species, indicate that this
      attribute together with other cell surface features may determine the hierarchy
      of virulence amongst the different Candida species.

PMID- 8534430
TI  - Binding of Galanthus nivalis lectin to Chlamydia trachomatis and inhibition of in
      vitro infection.
AB  - A glycoprotein present in Chlamydia trachomatis, serotype L1, elementary bodies
      (EBs) was earlier found to bind the lectin from Galanthus nivalis (GNA). In the
      present paper we investigate the interaction of GNA with chlamydial EBs and its
      effect on in vitro infectivity. The binding affinity was studied with 125I-GNA
      lectin. Within 15 min about 80% maximal binding was obtained. The chlamydia-GNA
      interaction was inhibited by alpha-methylmannoside, causing a decrease of about
      50% at 1 mM. Curve fit analyses indicated two types of binding sites for GNA on
      the EBs. The affinity to these differed by a factor of 15. The influence of the
      lectin on the ability of C. trachomatis to infect McCoy cells was also
      investigated. There was a GNA-dependent inhibition with a 50% reduction in the
      number of intracellular inclusions at 0.2 microM of the lectin. The findings
      indicate the presence of terminal mannose structures on the chlamydial surface at
      or in the proximity of the cell-binding domains. Mannose-binding proteins of
      eukaryotic cells could be important for the initial uptake of EBs.

PMID- 8534431
TI  - Quantification of the endotoxin-neutralizing capacity of serum and plasma.
AB  - A new procedure for quantifying the endotoxin-neutralizing capacity (ENC) of
      plasma or serum is described. Serially diluted samples were preincubated with
      endotoxin (lipopolysaccharide; LPS) and the sample dilution producing 50%
      inhibition of Tachypleus amebocyte lysate activation was measured by a Limulus
      peptide C enzyme-linked immunosorbent assay. The assay was not subject to
      interference from plasma or serum at a 500-fold dilution. The ENC of fresh sera
      from 120 healthy human donors, determined with Salmonella abortus LPS, had a
      median value of 7.7 kEU/ml (95% confidence limits 3-24 kEU/ml). Values for
      heparinized fresh plasma were close to those for the corresponding sera. Serum
      ENC varied greatly with different types of LPS. Neutralization of LPS by serum
      was rapid, heat-labile, and fully reversed by acidification. Addition of 2 mM
      EDTA to the serum diluent or pretreatment of LPS with 0.5% deoxycholate enhanced
      the ENC of serum about 25-fold or 10-fold respectively. The neutralization of LPS
      by polymyxin B or lysozyme could be demonstrated by the ENC assay, while that by
      human serum albumin, fibronectin or anti-LPS immunoglobulins was only detected in
      the presence of 2 mM EDTA. The kinetic changes of LPS and ENC during rabbit
      endotoxemia were also determined. The ENC assay may be used to study the
      significance of plasma ENC in Gram-negative infections and to identify the
      components contributing to plasma ENC.

PMID- 8534432
TI  - A Streptococcus agalactiae R protein analysed by polyclonal and monoclonal
      antibodies.
AB  - Unexpected cross-reactivity between two Streptococcus agalactiae (GBS) isolates
      formed the basis for purification of a GBS protein called the Ra antigen, and
      raising of murine monoclonal antibody (MAb) against Ra. The Ra protein was
      resistant to trypsin digestion, susceptible to pepsin digestion, formed a ladder
      like pattern of lines with a periodicity of approximately 8 kD on immunoblotting,
      was surface-localized in GBS strains, and was variably expressed by GBS. These
      characteristics provided evidence that the Ra antigen belonged to the R proteins
      of GBS. By testing of reference GBS isolates and antiserum, including an anti-R4
      protein serum, cross-reactivity was recorded consistent with the assumption that
      Ra is a R4 protein. The Ra/R4 protein also showed cross-reactivity with a
      previously described GBS protein called protein Rib (J. Exp. Med. 177: 1593-1603,
      1993). Several characteristics of the Ra/R4 protein were similar to those of the
      GBS protein c alpha, but the two proteins showed no cross-reactivity. The anti
      Ra/R4 MAb has proved useful in serosubtype determination of GBS of known serotype
      and should be a valuable tool for studying the immunobiological function of
      antibodies targetting the surface-localized Ra/R4 protein.

PMID- 8534433
TI  - A histological and immunohistological study of malarial placentas.
AB  - Sections of 18 malaria-infected placentas were stained with haematoxylin and
      eosin, periodic acid and methenamine silver, and immunohistochemically with
      monoclonal antibodies against human common leukocyte antigen, CLA (CD 45), B
      cells (CD 20, L 26), T cells (CD 45RO, UCHL-1) and collagen IV. Parasitized
      erythrocytes accumulated in the maternal villous spaces, with none in the foetal
      circulation. These were found in association with inflammatory leukocytes and
      pigments. Fibrinoid necrosis was more prevalent in the heavily infected
      placentas. Thickening and reduplication of foetal capillary basement membranes,
      and a decrease in leukocytes, including B and T cells, were seen in the heavily
      infected placentas. These findings are in keeping with previously reported
      depression of cellular and humoral immunity in patients with heavy parasitaemia.

PMID- 8534434
TI  - Up-regulation of CD44 and ICAM-1 expression on gastric epithelial cells by H.
      pylori.
AB  - Interaction between lymphocytes and epithelial cells may play a key role in
      Helicobacter pylori (H. pylori)-associated gastric mucosal inflammation. This
      interaction process is at least partially mediated by various cell adhesion
      molecules. The aims of the present study were to assess using flow cytometric
      analysis whether H. pylori directly or supernatants from H. pylori-activated
      peripheral blood mononuclear cells (PBMC) can affect the expression of adhesion
      molecules on the gastric epithelial cell line AGS in vitro. The results showed
      that resting AGS cells expressed CD44 and ICAM-1. Co-culture of AGS with H.
      pylori or cytokine-rich supernatants from H. pylori-activated PBMC resulted in up
      regulation of expression of CD44 and ICAM-1 on AGS cells. These data suggest that
      H. pylori directly and indirectly through inflammatory cytokines may contribute
      to alternations in adhesion molecule expression on gastric epithelial cells. This
      may be of pathological significance in H. pylori-associated gastric mucosal
      inflammation and carcinogenesis.

PMID- 8534435
TI  - Hyaluronan and procollagen type III aminoterminal peptide in serum and
      bronchoalveolar lavage fluid from patients with pulmonary fibrosis.
AB  - Previous studies of the collagen synthesis markers hyaluronan (hyaluronic acid)
      (HA) and procollagen type III aminoterminal peptide (PIIINP) in pulmonary
      fibrosis have reported elevated levels in bronchoalveolar lavage fluid (BALF) and
      suggested an association with disease activity. The objective of the present
      study was to evaluate whether HA and PIIINP in BALF and serum (S) correlated with
      paraclinical markers of disease activity (chest X-ray profusion score, pulmonary
      function tests (FEV1, FVC, TLC, DLCO)) in patients with pulmonary fibrosis. The
      material comprised 27 patients with biopsy-proven pulmonary fibrosis (12
      cryptogenic and 15 due to connective tissue diseases) and 24 control subjects
      with normal lung function. BAL was performed in the right middle lobe with 250 ml
      saline. HA and PIIINP were measured in the cell-free BALF supernatant and in
      serum. Patients had higher BALF-HA (mean 86 +/- 17 (SEM) micrograms/l) than
      controls (39 +/- 2 micrograms/l (p < 0.01)), higher BALF-albumin (124 +/- 24
      mg/l) than controls (58 +/- 4 mg/l (p < 0.01)) and higher BALF/S-HA ratio (2.4 +/
      0.6) than controls (1.2 +/- 0.6 (p < 0.05)). There were no significant
      differences respecting BALF-PIIINP, S-HA, or S-PIIINP. Patients (n = 14) with
      progressive disease had higher BALF-HA, higher BALF-albumin, higher S-PIIINP, and
      higher S-immunoglobulins than those with stable disease, but the differences did
      not reach statistical significance. Smokers (n = 18) had lower BALF-HA, lower S
      HA, lower S-PIIINP, lower S-immunoglobulins, and higher lung function tests than
      non-smokers, but the differences did not reach statistical significance. In
      patients, significantly positive correlations were found between BALF-HA and BALF
      albumin, between BALF-PIIINP and BALF-albumin, and a significantly negative
      correlation between S-PIIINP and TLC. None of the BALF or serum markers
      correlated with chest X-ray profusion score or any of the other lung function
      measurements. It is concluded that disease activity may be associated with
      elevated HA and PIIINP levels. Smoking may influence the immunological processes
      in pulmonary fibrosis and may be a confounder in studies of these patients.

PMID- 8534436
TI  - Broad-range PCR amplification and DNA sequence analysis reveals variable motifs
      in 16S rRNA genes of Mobiluncus species.
AB  - Using DNA primers based on highly conserved regions of bacterial 16S ribosomal
      RNA genes, a technique was established for detection of Mobiluncus species by
      polymerase chain reaction (PCR) and hybridization analysis. Part of the 16S rRNA
      genes of Mobiluncus mulieris, Mobiluncus curtisii and uncharacterized Mobiluncus
      strains were analyzed by broad-range PCR amplification and direct DNA sequencing
      analysis. Sequence comparison of the partial 16S rRNA genes of Mobiluncus
      curtisii, Mobiluncus mulieris and atypical Mobiluncus strains studied indicated
      genus and species-specific motifs within the variable regions V3, V4 and V9 of
      16S ribosomal DNAs. A Mobiluncus curtisii-specific primer, located within the
      variable region V3 of the 16S rRNA gene, was designed for Southern blot
      hybridization analysis of broad-range PCR products. Broad-range amplification
      combined with a M. curtisii-specific hybridization probe, Mob V3, distinguished
      between Mobiluncus curtisii, Mobiluncus mulieris, and atypical Mobiluncus
      strains.

PMID- 8534437
TI  - Bronchoalveolar lavage in radiologically detected diffuse lung disease.
      Diagnostic value of total and differential cell count in a series of 130
      patients.
AB  - During a 7-year period bronchoalveolar lavage (BAL) was performed as a routine
      diagnostic procedure at fiberoptic bronchoscopy in 172 consecutive patients with
      diffuse pulmonary lesions. In 42 patients, BAL was technically insufficient or
      data were incomplete. These patients were excluded. The remaining 130 patients
      consisted of 78 men and 52 women with a median age of 43 years (range 19-79); 59
      were smokers. They were divided into 6 groups: I. sarcoidosis (n = 77); II.
      cryptogenic fibrosing alveolitis (n = 16); III. secondary fibrosing alveolitis (n
      = 7); IV. malignancy (n = 7); V. allergic alveolitis (n = 6); VI. miscellaneous
      (n = 17). Group VI was not included in the statistical evaluation, which involved
      only the 113 patients in groups I-V. BAL was performed in a segment of the right
      middle lobe with 150-200 ml isotonic saline. The return fluid (BALF) was filtered
      through two layers of cotton gauze, and total and differential cell counts were
      assessed. Median BALF return volume was 67% (range 35-90). Eighty percent of the
      procedures were performed by the same operator. Total cell count displayed no
      significant difference amongst the five diagnostic groups (p = 0.06).
      Differential cell count displayed differences amongst the groups respecting
      macrophages (p = 0.002), lymphocytes (p = 0.0004), neutrophils (p = 0.0001) and
      eosinophils (p = 0.04). Patients with sarcoidosis had a higher percentage of
      lymphocytes, patients with secondary fibrosis a higher percentage of neutrophils,
      and patients with cryptogenic fibrosis a higher percentage of eosinophils than
      the other groups. Malignant cells were observed in BALF in 14.3% of patients with
      malignant lesions. Among the patients with sarcoidosis, 75% had a lymphocyte
      dominated BALF (> 10%) compared with 31% of the patients with cryptogenic
      fibrosis, 14% of the patients with secondary fibrosis, and 43% of the patients
      with malignancy. Dominance of neutrophils (> 10%) and/or eosinophils (> 5%) in
      BALF was observed in cryptogenic and secondary fibrosis. In most patients, BAL
      cannot provide a definite diagnosis, but may support the clinical suspicion of a
      specific diagnosis. In clinical practice, BAL seems to be of limited value in the
      diagnostic evaluation of radiologically detected diffuse, non-infectious
      pulmonary lesions.

PMID- 8534438
TI  - Perfluorocarbon heavy liquids.
AB  - Perfluorocarbon heavy liquids (PFCL) facilitate the transfer of intraocular
      fluids and other surgical manoeuvres in the posterior segment. The indications
      for their use have extended since first described in the management of giant
      retinal tears and proliferative vitreoretinopathy. We reviewed our personal
      experience and experimental evidence, including adverse effects, in order to
      identify the current role of PFCL in vitreoretinal surgery. High-density
      perfluorocarbon liquids represent a major advance in vitreoretinal surgery.
      Clinical experience and the results of experimental investigations have
      demonstrated their efficacy and safety as an intraoperative device.

PMID- 8534439
TI  - Screening for glaucoma in a Brisbane general practice--the role of tonometry.
AB  - OBJECTIVES: (1) To pilot, and evaluate, a tonometry training intervention for
      general practitioners; (2) to evaluate the efficacy of three types of tonometer
      (Perkins, Schiotz and Tonopen) in the hands of these general practitioners; (3)
      to evaluate the predictive value of tonometry in screening for glaucoma in a
      general practice population; and (4) to evaluate the acceptability of tonometry
      to general practice patients. DESIGN: After being trained, three general
      practitioners recruited 73 of their patients over 50 years of age to attend for
      measurement of intraocular pressure by tonometry. Intraocular pressure was
      initially measured by an ophthalmologist using the Goldmann applanation
      tonometer, and then recorded in random order by GPs using three types of
      tonometer--the Perkins, Schiotz and Tonopen. SETTING: A group general practice in
      a middle-class suburb in southern Brisbane. OUTCOME MEASURES: (1) Comparison of
      measurements on the Perkins, Schiotz and Tonopen tonometers with that of the
      'gold standard', the Goldmann Applanation tonometer; (2) prevalence of disc and
      perimetric abnormality suggestive of glaucoma among those patients with increased
      intraocular pressure; and (3) the acceptability of contact tonometry to general
      practice patients. RESULTS: There was considerable variability between
      intraocular values obtained across doctors and across instruments (6% to 95% of
      values within 4 mm of the 'gold standard'). The Schiotz tonometer provided the
      most uniform assessment of intraocular pressure across the groups. Nineteen of
      the 73 patients (26%) had intraocular pressures > or = 21 mmHg using the 'gold
      standard'. Of these, 18 were followed up with funduscopy, gonioscopy, repeat
      measurement of intraocular pressure and visual field assessment. Five had
      persistent elevations of intraocular pressure > or = 21 mmHg on subsequent
      assessment, and two had mild abnormalities of cup-disc ratio with normal fields
      on testing with Humphrey computerised perimetry. CONCLUSION: No one hand-held
      tonometer proved highly accurate in the hands of all three doctors. Even measured
      optimally, increased intraocular pressure alone was a poor predictor of glaucoma.
      Of the population screened, two patients (3%) showed evidence of mild cup-disc
      abnormality requiring follow-up.

PMID- 8534440
TI  - Brisbane GPs' perceptions of screening for primary open-angle glaucoma.
AB  - BACKGROUND: Primary open-angle glaucoma (POAG) is one of the three leading causes
      of blindness in Australia, often causing considerable visual field loss before
      the patient becomes symptomatic. Recent years have seen a quickening of public
      health interest in primary open-angle glaucoma. Our study evaluates the attitudes
      and skills of Brisbane GPs with regard to screening for POAG. OBJECTIVES: To
      evaluate general practitioners' current use of possible screening modalities for
      POAG. To evaluate general practitioners' attitudes to screening for POAG. To
      evaluate general practitioner's levels of satisfaction with their knowledge and
      skills in the diagnosis of common ophthalmological conditions. METHOD: A
      questionnaire was distributed to 130 randomly selected GPs in the Brisbane
      metropolitan area. Response rate was 94%. RESULTS: Tonometry and funduscopy were
      infrequently used in Brisbane general practice. Only 15% of the sample were
      satisfied with their current knowledge and skills concerning the detection of
      POAG. 88% felt that patients > 50 years should be screened for POAG and nominated
      a variety of sources -75% advocating ophthalmology screeners, 65% GP screeners,
      and 41% optometrist screeners. Ninety-nine per cent believed ophthalmologists
      should be treating glaucoma patients, and 57% believed GPs should have a role in
      management. Only 1% supported a therapeutic role for optometrists. Major
      perceived barriers to glaucoma screening in the elderly were the inaccuracy of
      current general practice screening tools (65%) and paucity of information
      concerning the desirability of screening (32%). CONCLUSION: Brisbane general
      practitioners believe patients > 50 years old should be screened for POAG. They
      advocated a role for screening by ophthalmologists, GPs and optometrists. Major
      perceived barriers to current screening in general practice are the inaccuracy of
      current general practice tools (65%) and paucity of information on the subject
      (32%). The majority (85%) requested further information and provision of skills
      in this area.

PMID- 8534441
TI  - Excimer laser surgery for myopia and myopic astigmatism.
AB  - Photorefractive keratectomy using the Summit Excimer Laser has been carried out
      on 1333 eyes with myopia or myopic astigmatism which have been followed up for
      six months or longer. Of those, 607 have been followed up for one year. Of the
      eyes with myopia or myopic astigmatism of up to 3 dioptres spherical equivalent,
      at one year 85.6% had unaided vision of 6/6, 97.2% 6/9 or better, and 99.4% 6/12
      or better. Of the eyes between -3.25 and -6.00 dioptres spherical equivalent at
      one year 72.1% achieved 6/6 vision unaided, 88.8% 6/9 or better, and 94.2% 6/12
      or better. Of the eyes between -6.25 and -10.00 dioptres, at one year 49.6%
      achieved 6/6 vision unaided, 76.1% 6/9 or better and 88.0% 6/12 or better. To
      achieve these figures, 28% of the patients had astigmatic keratotomy, either two
      or three weeks before photorefractive keratectomy, or at the same time as
      photorefractive keratectomy. Photorefractive keratectomy is as predictable as
      radial keratotomy in eyes of under 6 dioptres myopia, but is more predictable
      than radial keratotomy in higher myopia. Photorefractive keratectomy has the
      advantages of leaving an eye which is structurally sound, and without diurnal
      variation of focusing.

PMID- 8534442
TI  - Excimer laser lamellar keratoplasty.
AB  - PURPOSE: To evaluate a procedure using the excimer laser to perform lamellar
      keratoplasty to treat deep corneal scars in the central optical zone. To
      determine if excimer laser can safely prepare a smooth surface for the host bed
      and the donor button, assess the interface opacity and evaluate the effects of
      the ablation on the recipient's endothelial surface with the deeper ablation.
      METHODS: Nineteen rabbits underwent an excimer laser lamellar keratoplasty in one
      eye. The rabbits were followed for 9 to 12 weeks until they were sacrificed.
      RESULTS: Little opacity developed at the graft-host interface and scanning
      electron microscopy of the endothelial surface showed little difference between
      the treated and untreated areas or the endothelium of the untreated eyes.
      CONCLUSIONS: Our results suggest that the use of the excimer laser to treat
      corneas with deep stromal scars and normal endothelium is feasible. However, we
      have not proved that this technique will give a better result than conventional
      lamellar dissection methods.

PMID- 8534443
TI  - Scanning laser ophthalmoscopy of choroidal neovascularisation using indocyanine
      green.
AB  - BACKGROUND: Choroidal neovascularisation is an important cause of visual loss in
      age-related macular degeneration. Visualisation of these choroidal abnormalities
      with fluorescein angiography may be difficult, particularly if there is
      haemorrhage, excessive pigment, or excessive fluorescence. We report on our
      experience with indocyanine green (ICG) angiography in demonstrating choroidal
      neovascularisation. METHOD: Patients with suspected choroidal neovascularisation
      were assessed with indocyanine green angiography using the Rodenstock Scanning
      Laser Ophthalmoscope and results recorded on a videotape. Fluorescein angiograms
      were also obtained in a similar fashion. The angiograms were then compared.
      RESULTS: In some instances ICG angiography was able to demonstrate the margins
      and structure of choroidal neovascular membranes more clearly than fluorescein,
      particularly in the presence of haemorrphage, excessive fluorescence and blocked
      fluorescence. However, there were instances where it was difficult to interpret
      the choroidal abnormalities found. Some illustrative cases are discussed.
      CONCLUSION: We conclude that ICG angiography is a useful adjunct to fluorescein
      angiography in detection and delineation of choroidal neovascularisation, but
      that further study is needed.

PMID- 8534444
TI  - Comparison of stereo optic disc photographs from the Nidek 3-Dx and Zeiss retinal
      cameras.
AB  - OBJECTIVE: To compare the Zeiss retinal camera with the Nidek 3-Dx camera for
      photographic quality and stereo separation. SUBJECTS: Eleven subjects (22 eyes)
      were selected from patients referred for optic disc photography. METHODS: The
      subjects were photographed using the Nidek 3-Dx camera for simultaneous stereo
      photographs, and the 30 degrees field and 15 degrees field settings on the Zeiss
      retinal camera for sequential stereo photographs. Four ophthalmologists
      qualitatively scored the photographs on a five-point scale for stereo separation
      and photographic resolution and sharpness. The results from the four observers
      were averaged and the Friedman two-way analysis of variance used to analyse the
      results. CONCLUSIONS: It was found that the stereo separation is significantly
      better using the Nidek camera when compared with both the 30 degrees and 15
      degrees Zeiss results. There was no significant difference in photographic
      quality between the Nidek and Zeiss 30 degrees photographs. It was also found
      that the Zeiss 30 degrees images had a significantly higher quality than the
      Zeiss 15 degrees, which contradicted previous results.

PMID- 8534445
TI  - Amyloidosis of the conjunctiva.
AB  - BACKGROUND: Amyloid of the eyelid conjunctiva is an extremely rare condition
      which may result in chronic discomfort and multiple surgeries. METHODS: A
      retrospective study of four patients from Moorfields Eye Hospital is presented to
      assess the clinical features and results of surgical treatment. RESULTS: Three
      patients had persistent ocular irritation and required multiple surgical
      procedures for recurrent amyloid. However, one patient has been followed for
      nearly 30 years with relatively few symptoms, and has required only infrequent
      surgical intervention. All patients underwent debulking and ptosis surgery at
      least once. The more severe clinical course was not related to the type of
      amyloid protein present. Shave excision of recurrent tarsal conjunctival amyloid
      with split-thickness mucous membrane grafting was successfully tried in one
      patient in order to minimise postoperative cicatrisation of the posterior
      lamella. CONCLUSION: The clinical course of patients with eyelid amyloid may vary
      greatly. Management should be conservative when possible, but surgery is an
      integral part of management since debulking of amyloid deposits and ptosis
      surgery was required in all patients in this series.

PMID- 8534446
TI  - Acute glaucoma--1941.
AB  - PURPOSE: To describe the treatment of acute glaucoma before the technological and
      pharmacological advances that followed World War 2. METHOD: A narrative of
      personal experience is presented. CONCLUSIONS: In 1941, acute congestive glaucoma
      received heroic treatment - strong miotics, blood-letting by leeches, purging
      with mercury. If satisfactory response did not occur within four hours, a broad
      iridectomy was performed on the hard, congested eye. Affected eyes commonly
      remained blind or with severely reduced vision.

PMID- 8534447
TI  - Ultrasound biomicroscopic features of spherophakia.
AB  - BACKGROUND: Spherophakia is an uncommon diagnosis. This is the first case report
      of spherophakia evaluated by ultrasound biomicroscopy. METHODS: Ultrasound
      biomicroscopy is a new diagnostic technique developed by one of the authors and
      provides images with microscopic resolution of the anterior segment. A patient
      with spherophakia was evaluated by ultrasound biomicroscopy (Zeiss-Humphrey,
      50MHz) before and after YAG laser iridotomy. RESULTS: Ultrasound biomicroscopic
      assessment revealed a shallow anterior chamber, a very steep anterior lens
      curvature, iridolenticular contact, elongated zonules, and an increased distance
      between the lens equator and the ciliary processes. Angle closure glaucoma was
      due to a pupil block mechanism. The pupil block was relieved by YAG laser
      iridotomy. CONCLUSIONS: Ultrasound biomicroscopy is a useful technique to confirm
      the diagnosis of spherophakia. The pupil block in spherophakia is relieved by YAG
      laser iridotomy.

PMID- 8534448
TI  - Acute irreversible cataracts in diabetes mellitus.
AB  - AIM: To report an unusual cause of blindness in a patient newly diagnosed with
      insulin-dependent diabetes mellitis (IDDM). METHOD: A 19-year-old man presented
      with classical symptoms of hyperglycaemia. On presentation his visual acuity and
      ophthalmic examination were normal. He was prescribed twice-daily insulin therapy
      and six weeks later presented with visual loss. He had only light and dark
      perception and was noted to have bilateral, dense, mature cataracts. OUTCOME:
      Right cataract extraction and intraocular lens implant was performed with
      restoration of vision. Despite good diabetic control the left cataract did not
      resolve. Seven months later the patient had left cataract extraction and
      intraocular lens implant, again with good result. CONCLUSION: Mature dense
      cataracts rarely occur and appear not to resolve with control of hyperglycaemia,
      as in this case, and require surgical treatment.

PMID- 8534449
TI  - Phialophora corneal ulcer.
AB  - BACKGROUND: A corneal fungal ulcer which appeared to be quite superficial
      clinically, was found by histologic examination to unexpectedly involve the full
      thickness of the cornea. METHODS: A patient with an apparent superficial corneal
      fungal ulcer due to Phialophora species was resistant to topical and intravenous
      antifungal therapy. RESULTS: Penetrating keratoplasty cured the condition with
      retention of normal vision with a follow-up of two years. CONCLUSIONS: If
      keratomycosis is unresponsive to topical and intravenous antifungal therapy,
      penetrating keratoplasty may be required to eliminate the infection. Resistance
      to medical therapy might suggest presence of fungus far deeper in the cornea than
      suspected clinically.

PMID- 8534450
TI  - Corneal tattooing revisited: excimer laser in the treatment of unsightly
      leucomata.
AB  - BACKGROUND: Corneal tattooing, a procedure first used by Galen in the treatment
      of unsightly leucomata, has in recent times received relatively little attention
      due to major advances in intraocular and corneal surgery. Resurrection of the
      technique, however, may be reasonably considered in 'high risk' cases of
      leucomata or leucocoria where corneal transplantation would lead to rejection and
      failure, or, in eyes with no visual potential, where removal of cosmetically
      unacceptable dense, white cataracts carries an unreasonable risk of phthisis
      bulbi or sympathetic ophthalmitis. METHODS: Corneal tattooing requires the
      accurate and limited removal of corneal epithelium to act as the tattoo bed and
      unfortunately, if removal of the epithelium exceeds, or goes beyond the
      circumference of, the chosen area, a ragged cosmetically less pleasing 'pupil' is
      created. The excimer laser appears to be an ideal tool to create a perfectly
      circular corneal bed to improve upon older techniques. CONCLUSION: We report, for
      the first time, an updated, simple and improved technique for successful corneal
      tattooing using excimer laser technology.

PMID- 8534451
TI  - Reversible ophthalmoplegia in CPEO.
AB  - PURPOSE: To present a case of improvement of ocular motility in a patient with
      chronic progressive external ophthalmoplegia (CPEO) with Coenzyme Q10. METHODS:
      Coenzyme Q10 300 mg daily was given for three years with a three-day trial period
      of 200 mg daily after one year. Ocular ductions were measured by synoptophore.
      RESULTS: Ocular ductions improved with treatment with Coenzyme Q10. CONCLUSION:
      Coenzyme Q10, is effective in limiting the severity of ophthalmoplegia in this
      case.

PMID- 8534452
TI  - Primary extramedullary plasmacytoma of the orbit.
AB  - BACKGROUND: We report a case of extramedullary plasmacytoma of the orbit. This is
      a rare tumour which has uncommonly presented in the orbit. CASE REPORT: A 58-year
      old woman presented with painless proptosis, upper lid swelling and ptosis.
      Incisional biopsy was performed. Clinical findings and investigations were
      correlated to establish the diagnosis. Treatment consisted of 35 Gy external beam
      radiotherapy. CONCLUSIONS: This condition is considered to be of low grade
      malignancy and as such can be regarded as a separate entity to multiple myeloma
      involving the orbit or solitary myeloma of bone in terms of treatment and
      prognosis.

PMID- 8534453
TI  - Bronchopulmonary atypical carcinoid tumour metastatic to the orbit.
AB  - BACKGROUND: Bronchopulmonary carcinoid tumours metastatic to the orbit are rare.
      A case is presented demonstrating presentation, histopathology and treatment.
      METHODS: A 64-year-old man with a history of bronchopulmonary atypical carcinoid
      presented with an orbital mass. The nature of this metastasis was confirmed with
      histology and it was surgically excised and, in addition, local radiotherapy and
      chemotherapy were administered. RESULTS: There was a good response to the
      treatment for the orbital mass but other metastases developed, causing death.
      CONCLUSIONS: In this case of atypical carcinoid, orbital metastasis was the first
      sign of disease progression. Histological confirmation of the diagnosis was
      important in this case to allow planning of oncological therapy and for
      appropriate patient counselling. A good local response was obtained with a
      combination of surgical excision, local radiotherapy and chemotherapy. The
      systemic prognosis remains poor in cases of metastatic bronchopulmonary atypical
      carcinoid tumour, in contrast to typical carcinoid.

PMID- 8534454
TI  - Clostridium perfringens keratitis after penetrating keratoplasty.

PMID- 8534455
TI  - Suture repair of involutional entropion.

PMID- 8534456
TI  - Bilobed flap repair in medial canthal reconstruction.

PMID- 8534457
TI  - Blindness and trachoma in South Australia.

PMID- 8534458
TI  - Anesthesia for interventional neuroradiology.
AB  - STUDY OBJECTIVE: To review the anesthetic management and the occurrence and
      treatment of complications in patients undergoing interventional neuroradiologic
      procedures for the treatment of intracranial vascular lesions. DESIGN:
      Retrospective chart review of 115 charts from 1988 to 1992. SETTING: University
      hospital. MEASUREMENTS AND MAIN RESULTS: Charts were reviewed for information
      regarding the anesthetic management, monitoring techniques, complications,
      treatment of complications, and clinical outcome. Group 1 patients (n = 92) were
      managed by an anesthesiologist; 8 received general anesthesia and 84 had
      conscious sedation. Group 2 patients (n = 70) were cared for by a
      neuroradiologist; 37 received intravenous analgesia (fentanyl) and 33 received no
      sedation other than premedication (benzodiazepine). No episodes of anesthetic or
      drug-related complications were documented. Complications directly related to
      technical aspects of the procedure were documented in 33 (20%) cases, 19 (21%) in
      Group 1 and 14 (20%) in Group 2. These complications consisted of ischemia (n =
      14), hemorrhage (n = 9), catheter misplacement (n = 8), and pulmonary embolism (n
      = 2). Four patients, two in each group, required urgent assessment by an
      anesthesiologist. CONCLUSIONS: There was no difference in the incidence of
      complications between the two groups. As the use of interventional neuroradiology
      increases, the anesthesiologist will be more involved in the elective or
      emergency treatment of these patients.

PMID- 8534459
TI  - Doxacurium block is not influenced by age.
AB  - STUDY OBJECTIVE: To determine the influence of aging on the efficacy and safety
      of doxacurium. DESIGN: Open, randomized, phase III study. SETTING: Inpatient
      ophthalmic surgery clinic at a university medical center. PATIENTS: 30 elderly
      patients (65 years or older) compared with a control group of 30 younger patients
      (18 to 64 years). INTERVENTIONS: An elective ophthalmological surgical
      intervention of more than 2 hours' expected duration with general anesthesia with
      isoflurane. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function after a bolus
      dose of doxacurium was monitored electromyographically. No significant difference
      was observed in maximum block achieved or onset time. Clinical duration of
      neuromuscular block was similar in both groups. Hemodynamic changes were
      clinically unimportant. CONCLUSION: The use of doxacurium in elderly patients is
      possible with no need for dose adjustment. Doxacurium might be a good choice for
      patients with cardiac disease who are scheduled for long surgical procedures.

PMID- 8534460
TI  - The effect of epidural blood patch on hearing loss in patients with severe
      postdural puncture headache.
AB  - STUDY OBJECTIVE: To determine the immediate effect of epidural blood patch (EBP)
      on the hearing loss that can accompany postdural puncture headache (PDPH).
      DESIGN: Prospective open study. SETTING: Anesthetic and otolaryngologic
      departments at a university hospital. SUBJECTS: 16 patients who developed severe
      PDPH following either myelography or spinal anesthesia. INTERVENTIONS: Epidural
      injection of 15 ml of autologous blood. MEASUREMENTS AND MAIN RESULTS: Audiometry
      at 250, 500, 1,000, 2,000, 4,000, and 8,000 Hz before and one hour after the
      epidural blood patch was performed. Hearing was significantly improved in 12 of
      the 16 patients studied. The improvement was at least 10 dB at two or more
      consecutive frequencies, or 5 dB at four or more consecutive frequencies.
      CONCLUSION: Epidural blood patch improves hearing within one hour in the majority
      of patients with severe PDPH.

PMID- 8534461
TI  - Ketorolac for early postoperative analgesia.
AB  - STUDY OBJECTIVE: To determine the efficacy and speed of onset of analgesia of a
      single dose of intravenous (IV) or intramuscular (IM) ketorolac tromethamine
      following major orthopedic surgery. STUDY DESIGN: Double-blind, randomized,
      placebo-controlled trial. SETTING: A district general hospital in England.
      PATIENTS: 112 patients aged 18 to 80 years suffering moderate or severe pain
      following orthopedic surgery. INTERVENTIONS: Patients were randomized to receive
      30 mg ketorolac IV, 30 mg ketorolac IM, or placebo following surgery.
      MEASUREMENTS AND MAIN RESULTS: Verbal pain intensity scores were performed prior
      to admission to the study, then frequently for the first 45 minutes following
      administration of study medication, and subsequently at hourly intervals. Times
      to request for further analgesia were noted. Patient assessment of overall
      acceptability and pain relief of the study medication was recorded. There was no
      statistical difference in speed of onset of analgesia between the ketorolac
      groups and placebo. Median (range) times to first analgesic following study drugs
      were: ketorolac IV 45 minutes (9 to 1440 minutes), ketorolac IM 34 minutes (10 to
      1440 minutes), placebo 24 minutes (10 to 615 minutes). There was a statistically
      significant difference between the ketorolac groups and placebo (ketorolac IV vs.
      placebo, p < 0.01; ketorolac IM vs. placebo, p = 0.03). Patient assessment of
      overall acceptability and pain relief was significantly better for IV ketorolac
      compared with placebo (p < 0.01). By 6 hours, 78% of the IV ketorolac group and
      95% of the IM ketorolac and placebo groups required further analgesia.
      CONCLUSIONS: Despite high patient acceptability compared with placebo, the use of
      ketorolac as the sole analgesic failed to control postoperative pain following
      major orthopedic surgery. IV administration of ketorolac conferred no advantages
      over the IM route with regard to efficacy or speed of onset.

PMID- 8534462
TI  - Femoral nerve "sheath" for inguinal paravascular lumbar plexus block is not found
      in human cadavers.
AB  - STUDY OBJECTIVE: To determine if a femoral nerve sheath capable of conveying
      local anesthetic to the lumbar plexus and the obturator nerve exists in human
      cadavers. DESIGN: Injection of methylene blue dye into the femoral nerves of
      human cadavers followed by dissection and observation of dye distribution.
      SETTING: University medical center pathology department autopsy room. PATIENTS:
      Six fresh adult cadavers about to undergo postmortem examination. INTERVENTIONS:
      Both femoral nerves of six fresh cadavers were injected with either 20 ml or 40
      ml of dye. The abdomen was opened and distribution of the dye was observed.
      MEASUREMENTS AND MAIN RESULTS: In all of the cadavers studied there was no
      evidence of a femoral nerve sheath capable of conveying methylene blue dye to the
      lumbar plexus. Both 20 ml and 40 ml of dye injected into the femoral nerve failed
      to reach the lumbar plexus or the obturator nerve. When 40 ml of dye was injected
      it always stained the femoral nerves, it usually stained the lateral femoral
      cutaneous nerves, but it never stained the obturator nerves. CONCLUSIONS: A
      femoral nerve sheath capable of conveying a solution to the cadaver lumbar plexus
      does not exist in human cadavers. Dye injected into the cadaver femoral nerve
      does not reach either the lumbar plexus or the obturator nerve. When 40 ml of
      methylene blue dye is injected into the cadaver femoral nerve, some dye usually
      diffuses under the iliacus muscle fascia to the lateral femoral cutaneous nerve.
      This study indicates that in patients the "3-in-1 block" always blocks the
      femoral nerve, it usually blocks the lateral femoral cutaneous nerve, but it
      probably does not block the lumbar plexus or the obturator nerve.

PMID- 8534463
TI  - Epidural scopolamine administration in preventing nausea after epidural morphine.
AB  - STUDY OBJECTIVE: To determine the effectiveness of epidural scopolamine in
      preventing nausea and vomiting in patients receiving epidural morphine. DESIGN:
      Randomized, double-blind study. SETTING: Inpatient surgery clinic at a regional
      general hospital. PATIENTS: 50 patients undergoing major abdominal and lower limb
      surgery. INTERVENTIONS: Morphine alone 2.5 to 4 mg was administered via epidural
      catheter to one group, while the other group received morphine plus scopolamine
      0.25 mg via epidural catheter. MEASUREMENTS AND MAIN RESULTS: Occurrence of
      nausea and vomiting was recorded during the first postoperative day. Compared
      with the morphine alone group, the incidence of nausea and vomiting was
      significantly lower in the morphine plus scopolamine group without difference in
      the adequacy of analgesia. CONCLUSION: Epidural scopolamine can be used as an
      adjunct to epidural morphine in effectively reducing the incidence of
      postoperative nausea and vomiting.

PMID- 8534464
TI  - Effect of intrathecal sufentanil on isoflurane requirements during lower
      abdominal surgery.
AB  - STUDY OBJECTIVE: To determine the effect of intrathecal sufentanil on volatile
      anesthetic requirements during lower abdominal surgery. DESIGN: Randomized,
      double-blind study. SETTING: Military tertiary care hospital. PATIENTS: 15 female
      patients, ASA status I and II, undergoing elective lower abdominal surgery.
      INTERVENTIONS: After induction of anesthesia, each patient had a lumbar puncture
      performed with a 24-gauge Sprotte needle through a Tuohy needle positioned in the
      epidural space to receive either intrathecal sufentanil 10 micrograms or
      intrathecal normal saline (control). An epidural catheter was then placed for use
      in postoperative analgesia. Anesthesia was maintained in all patients with
      isoflurane, air, and oxygen. Gas flows were constant and the isoflurane
      concentration was adjusted at 5-minute intervals to maintain systolic blood
      pressure within 20% of preoperative baseline. MEASUREMENTS AND MAIN RESULTS: The
      mean end-tidal isoflurane concentration during the first hour of surgery was
      significantly lower in the sufentanil group (0.74 +/- 0.02%) compared with the
      control group (1.05 +/- 0.03%) (p = 0.006), an overall reduction of 28% in the
      isoflurane requirement. CONCLUSION: Prior administration of intrathecal
      sufentanil significantly decreases the isoflurane requirement in surgical
      patients, in addition to its previously demonstrated rapid onset and receptor
      efficacy.

PMID- 8534465
TI  - Use of analgesics during propofol sedation: a comparison of ketorolac, dezocine,
      and fentanyl.
AB  - STUDY OBJECTIVE: To evaluate the comparative efficacy and side effect profile of
      ketorolac 60 mg, dezocine 6 mg, and fentanyl 100 micrograms when used as
      analgesic supplements to a propofol infusion during monitored anesthesia care
      (MAC). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING:
      Ambulatory surgery facility at a university medical center. PATIENTS: 80
      outpatients undergoing breast biopsy or inguinal herniorraphy procedures under
      MAC. INTERVENTIONS: All patients received midazolam 2 mg intravenously (IV)
      followed by 1 ml of the study medication containing either dezocine 3 mg IV,
      ketorolac 30 mg IV, fentanyl 50 micrograms IV, or normal saline. A propofol
      infusion was initiated at 75 micrograms/kg/min and then varied to maintain a
      stable level of sedation (i.e., Observer Assessment of Alertness/Sedation scale
      score of 3). An additional 1 ml of the same study medication was administered IV
      2 to 3 minutes prior to infiltration of the local anesthetic solution. During the
      operation, supplemental (rescue) medication consisted of fentanyl 25 micrograms
      IV, bolus injections in all four treatment groups. MEASUREMENTS AND MAIN RESULTS:
      Propofol infusion and supplemental fentanyl dosage requirements, oxygen
      saturation values, respiratory rates, recovery times, and postoperative side
      effects were recorded. Visual analog scales were used to assess sedation,
      anxiety, pain, and nausea preoperatively (baseline), upon entry into the
      postanesthesia care unit, and at 30-minute intervals until discharge. The
      fentanyl and dezocine groups required lower average infusion rates of propofol to
      maintain a stable level of sedation than the control (saline) group. The saline
      and ketorolac groups required rescue analgesic medication more frequently and/or
      larger supplemental dosages of fentanyl than the two opioid analgesic treatment
      groups. Compared with the three analgesic treatment groups, postoperative pain
      scores were only marginally higher in the control group. Ketorolac-treated
      patients had consistently (but not significantly) shorter recovery times to oral
      intake, ambulation, and discharge than those in the dezocine or fentanyl groups.
      No postoperative nausea, vomiting, or pruritus was reported in the ketorolac
      group. CONCLUSION: Compared with ketorolac 60 mg, fentanyl 100 micrograms and
      dezocine 6 mg produced a greater decrease in the propofol sedation requirement
      during MAC. However, the use of ketorolac in combination with propofol for MAC
      was associated with an improved recovery profile.

PMID- 8534466
TI  - A comparison of EMLA cream versus nitrous oxide for pediatric venous cannulation.
AB  - STUDY OBJECTIVE: To compare the analgesic and anxiolytic effects of nitrous oxide
      (N2O) when inhaled by face mask with those of a cutaneous application of a
      eutectic mixture of local anesthetics (EMLA) cream with lidocaine and prilocaine
      during pre-operative venous cannulation in children. DESIGN: Prospective,
      randomized study. SETTING: Outpatient presurgical area and operating rooms of a
      freestanding children's hospital. PATIENTS: 50 unpremedicated ASA status I and II
      outpatients, aged 6 to 12 years, undergoing an elective surgical procedure.
      INTERVENTIONS: Each patient received either 70% N2O in 30% oxygen (O2)
      administered by face mask for 120 seconds or an application of 2.5 g of EMLA
      cream under an occlusive dressing for a minimum of 60 minutes. All patients then
      underwent a single attempt at venous cannulation in the dorsum of the hand with a
      22-gauge intravenous catheter. MEASUREMENTS AND MAIN RESULTS: A visual analog
      scale (VAS) pain score (0 to 100) was generated by the investigator and
      subsequently obtained from each patient immediately after the venous cannulation
      was completed. The pain scores generated by the investigator were significantly
      lower in the N2O group than the EMLA cream group (p = 0.001). When compared with
      the patients in the EMLA cream group, the patients in the N2O group also self
      reported significantly lower VAS pain scores (p = 0.006). CONCLUSIONS: N2O
      administered by face mask appears to provide greater anxiolysis and attendant
      superior analgesia for pediatric venous cannulation than a cutaneous application
      of EMLA cream.

PMID- 8534467
TI  - Factors that influence an anesthesiologist's decision to cancel elective surgery
      for the child with an upper respiratory tract infection.
AB  - STUDY OBJECTIVE: To examine factors that anesthesiologists consider when making
      decisions regarding elective surgery cancellation of the pediatric patient with
      an upper respiratory infection (URI). DESIGN: Questionnaire survey. SETTING:
      Anesthesiology departments and/or practices throughout the United States.
      PARTICIPANTS: 212 anesthesiologist members of the Society for Pediatric
      Anesthesia (SPA). MEASUREMENTS AND MAIN RESULTS: A total of 400 questionnaires
      were mailed to anesthesiologists randomly selected from the membership of the
      SPA. Of these questionnaires, 212 (54%) were completed and returned. Of these
      respondents, 71 (34.5%) reported that they seldom (1% to 25% of the time)
      cancelled cases due to an URI, and 43 (20.9%) stated that they usually (76% to
      99% of the time) cancelled in the event of an URI. Two respondents (1%) reported
      never cancelling due to an URI, and six (2.9%) stated that they always cancelled.
      Frequency of cancellation was independent of type of practice. However,
      anesthesiologists who had been in practice for more than 10 years were
      significantly more likely to cancel than those who had been in practice for less
      than 10 years (p < 0.05). Factors that were considered most important in making
      decisions regarding cancellation included the urgency of the surgery and the
      presence of asthma. Other important considerations included fear of complications
      and the anesthesiologist's previous experience anesthetizing children with URIs.
      Factors related to the economics and inconvenience of cancellation did not
      influence the decision to cancel surgery. These factors included distance
      traveled, cost of cancellation, attitude of the parents, fear of litigation, and
      pressure to complete cases expediently. CONCLUSIONS: The results of this survey
      demonstrate a wide range of opinions and approaches to this enduring clinical
      dilemma. However, it appears that the practice of cancelling elective surgery for
      children with URIs may be changing over time, since younger anesthesiologists
      appear to cancel less often than their more experienced counterparts. It is hoped
      that this information will be useful to practioners in their evaluation and
      management of children with colds and will stimulate further investigation into
      this important clinical problem.

PMID- 8534468
TI  - A post-anesthetic discharge scoring system for home readiness after ambulatory
      surgery.
AB  - STUDY OBJECTIVE: To evaluate the validity and reliability of an objective scoring
      system, the Post-Anesthetic Discharge Scoring System (PADSS), which was compared
      against existing Clinical Discharge Criteria in the ambulatory surgery unit of
      our hospital. DESIGN: randomized, open study. SETTING: Ambulatory surgery unit at
      a university teaching hospital. PATIENTS: 247 ambulatory surgery patients
      undergoing general anesthesia. INTERVENTIONS: One hour after the operation, the
      initial assessment using PADSS and the Clinical Discharge Criteria was made by an
      independent observer. Evaluations were repeated at 30-minute intervals until
      patients obtained a Post-Anesthetic Discharge Score of at least 9 and fulfilled
      the Clinical Discharge Criteria. MEASUREMENTS AND MAIN RESULTS: There was a close
      correlation between the end of anesthesia to time patients were fit for discharge
      using either PADSS or the Clinical Discharge Criteria (Pearson's Correlation
      Coefficient r = 0.89). The internal consistency reliability of PADSS (alpha =
      0.65) was superior to that of the Clinical Discharge Criteria (alpha = 0.14).
      CONCLUSIONS: We have found PADSS to have superior measurement scaling and
      diagnostic properties.

PMID- 8534469
TI  - The demographics of inpatient pediatric anesthesia: implications for
      credentialing policy.
AB  - STUDY OBJECTIVE: To examine the demographics of inpatient anesthesia care for
      infants and children in a specific region to determine if there were sufficient
      numbers of procedures to permit credentialing to take place, as a first step in
      understanding the consequences of implementing credentialing policies based on
      caseload. DESIGN: Retrospective computerized review of discharge abstracts.
      SETTING: All hospitals in northern California. MEASUREMENTS AND MAIN RESULTS:
      Surgical procedures and date of surgery were linked to create "procedure-days."
      Each procedure-day counted as one anesthesia case. Annual hospital caseloads
      (procedure-days) were tabulated for three separate age subgroups under six years
      of age. The proximity of hospitals with smaller surgical volumes to those with
      larger volumes was determined. Of the 205 hospitals in the region, 162 had at
      least one procedure-day for children less than 6 years of age for a total of
      14,435 procedure-days (anesthesia cases). For each of three age groups studied--0
      to 6 months, 7 to 24 months, and 25 to 72 months--85%, 90%, and 81%,
      respectively, of hospitals had caseloads of 1 to 50 per year. When procedure days
      from all three age groups were totalled, 59% of hospitals had less than 20 cases
      per year and 72% of hospitals had less than 50 cases per year; 86% of hospitals
      had less than 100 cases per year. Of hospitals with less than 100 cases per year,
      75% were within 50 miles of a hospital with more than 100 cases. CONCLUSIONS:
      Performance based credentialing for pediatric anesthesia based on caseload may be
      problematic for many hospitals due to the distribution of cases: a majority of
      hospitals care for a few children, and most children are cared for in a few
      hospitals.

PMID- 8534470
TI  - Cardiac arrest after oxymetazoline nasal spray.
AB  - Oxymetazoline nasal spray is a potent alpha 1-adrenergic agonist commonly used to
      vasoconstrict blood vessels in the nasal mucosa. In this incident, oxymetazoline
      nasal spray 0.025% was administered to a 2-year-old patient during general
      anesthesia for nasal endoscopy. Severe hypertension with reflex bradycardia
      progressed to sinus arrest and was successfully treated with alropine and
      cardiopulmonary resuscitation. Decreasing the dose of oxymetazoline and
      pretreatment with an anticholinergic is recommended.

PMID- 8534471
TI  - Transient neonatal myasthenia gravis and pyloric stenosis.
AB  - The case report describes the occurrence of hypertrophic pyloric stenosis in a
      premature infant with neonatal myasthenia gravis. The infant presented for
      pyloromyotomy on the nineteenth day of life. Diagnosis of myasthenia gravis was
      made based on maternal history and clinical findings of poor muscle tone, weak
      suck, and weak cry. The anesthetic management is discussed with reference to the
      problems of newborn myasthenia gravis and pyloric stenosis as they relate to
      anesthetic drugs and techniques.

PMID- 8534472
TI  - Understanding cost analyses: Part 1. A practitioner's guide to cost behavior.

PMID- 8534473
TI  - Legal issues in transfusing a Jehovah's Witness patient following cesarean
      section.

PMID- 8534474
TI  - Nicardipine: applications in anesthesia practice.
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.
      Nicardipine has been used to control blood pressure intraoperatively in response
      to tracheal intubation and in the postoperative period. Various patient
      populations have been included such as major vascular and cardiovascular surgery.
      It has also been used as an agent for controlled hypotension. Preliminary
      experience suggests that nicardipine provides safe and effective control of
      perioperative blood pressure. The basic pharmacology and physiology of the most
      recently released calcium channel antagonist, nicardipine, is reviewed, and its
      applications in clinical anesthesia and interaction with other anesthetic drugs
      are discussed.

PMID- 8534475
TI  - Ralph Waters and the beginnings of academic anesthesiology in the United States:
      the Wisconsin Template.
AB  - The University of Wisconsin, Madison, was one of the few places offering
      postgraduate training in the science and art of anesthesia in the late 1920s and
      1930s. Weaving together clinical and basic science research, and fully supported
      by his surgical colleagues, Ralph Waters was able to create the first collegiate
      based academic anesthesiology department. While Waters' department was an
      important milestone establishing anesthesia within the university setting, it did
      not guarantee true academic standing nationwide. For that to occur, Waters
      realized that it was necessary to establish other academic departments across the
      country. Attempting to replicate the department at his university. Waters
      searched for institutions where surgeons desired an academic anesthesia
      department. Additionally, he sought basic scientists ready to collaborate in
      scientific research in anesthesiology and a brisk clinical service. Successful
      application of the Wisconsin model was best reflected in the work of Waters'
      academic descendants: "sons" Emery Rovenstine and Robert Dripps, and "grandsons"
      Stuart Cullen and Emanuel Papper.

PMID- 8534476
TI  - Managing pharmaceutical sales activities in an academic anesthesiology
      department.
AB  - To contain costs, departments of anesthesiology must control the use of new,
      expensive drugs. Conflicts with pharmaceutical companies can arise when they
      promote drug sales. Pharmaceutical company sales represent anesthesiology
      department expenses. Anesthesiologists hold diverse opinions on this clash of
      interests, on the proper roles of pharmaceutical sales representatives in
      anesthesiology departments, and on the ethics of accepting industry gifts. Our
      department has managed pharmaceutical sales activities by encouraging discussion
      of the ethics and legal limits of industry gifts, by banning sales
      representatives from bringing food into the department, and by adopting The
      American Medical Association Guidelines on Gifts.

PMID- 8534477
TI  - A simple method of blood pressure determination in pediatric patients when
      automated noninvasive blood pressure measurement fails.

PMID- 8534478
TI  - Congenital complete tracheal rings: a cause of difficult tracheal intubation.

PMID- 8534479
TI  - Cost-effectiveness analysis of antiemetic therapy for ambulatory surgery.

PMID- 8534480
TI  - Gene therapy approaches for inherited and acquired lung diseases.
AB  - Gene therapy is the treatment of any disorder or pathophysiologic state based
      upon the transfer of genetic information. The lung represents a major target of
      gene therapy for the treatment of genetic disorders such as cystic fibrosis and
      alpha 1-antitrypsin deficiency. Other diseases are also being targeted, including
      pulmonary inflammation, surfactant deficiency, pulmonary hypertension, lung
      cancer, and malignant mesothelioma. This review will examine some general
      concepts regarding gene transfer and gene therapy, provide an overview of the
      current vectors being developed to achieve safe and efficient gene transfer, and
      summarize the ongoing work to apply this new technology to the treatment of both
      inherited and acquired pulmonary diseases. Although tremendous progress has been
      made in the ability to successfully transfer genes to cells, there are several
      unresolved problems limiting the clinical application of this technology to human
      pulmonary disease. However, as vector technology evolves, gene therapy may become
      a reality for a number of lung diseases.

PMID- 8534481
TI  - Mucociliary differentiation of serially passaged normal human tracheobronchial
      epithelial cells.
AB  - The goal of our studies was to establish procedures for subculturing normal human
      tracheobronchial epithelial (NHTBE) cells without compromising their ability to
      differentiate into mucous and ciliated cells (i.e., differentiation competence)
      and to study the regulation of airway secretions by epidermal growth factor (EGF)
      and retinoic acid (RA). Primary NHTBE cells were obtained from a commercial
      source and subcultured repeatedly in serum-free medium on plastic tissue culture
      dishes. The subcultured cells were tested after every passage for differentiation
      competence in air-liquid interface (ALI) cultures. The apical secretions of
      cultured NHTBE cells were characterized by immunoblotting, Western blotting, or
      enzyme-linked immunosorbent assay using a variety of antibodies. They contained
      mucin-like materials as well as lysozyme, lactoferrin, and secretory leukocyte
      protease inhibitor (SLPI). We found that an EGF concentration of 25 ng/ml, which
      is commonly used in airway cell cultures, adversely affected growth, mucin
      production, and morphology of ALI cultures and that RA was essential for
      mucociliary differentiation. Without RA, the epithelium became squamous and mucin
      secretions decreased 300- to 900-fold. In contrast, secretion of lysozyme,
      lactoferrin, and SLPI was significantly increased in RA-depleted cultures. Cells
      of passage 2 (P-2) through P-4 remained competent to differentiate into mucous
      and ciliated cells when grown in ALI cultures. However, mucin secretion and
      ciliagenesis decreased in P-3 and P-4 cell cultures and P-3 but not P-4 cell
      cultures exhibited bioelectric properties characteristic of airway epithelium. We
      concluded that P-2 and P-3 NHTBE cell cultures retain many important features of
      normal airway epithelium. This enables one to conduct many studies of airway cell
      biology with a greatly expanded (6,000-fold) cell pool.

PMID- 8534482
TI  - Regulation of mucociliary differentiation of rat tracheal epithelial cells by
      type I collagen gel substratum.
AB  - Adult rat tracheal epithelial cells plated at low density on type I collagen gel
      coated permeable membranes in air-liquid interface cultures rapidly proliferate
      to reach high cell densities and display a pseudostratified mucociliary
      epithelium after 2 wk in culture. To determine the importance of exogenous
      extracellular matrix for RTE cell growth and differentiation, RTE cells were
      seeded on uncoated or type I collagen gel-coated membranes. Growth rate and
      plateau cell densities were similar under these two conditions; however, RTE cell
      attachment was twofold higher on type I collagen gel-coated membranes. Cell
      distribution during log growth was significantly different, with numerous small
      colonies observed on Giemsastained uncoated membranes and fewer, larger colonies
      observed on type I collagen gel-coated membranes. Under both conditions, the
      epithelial morphology was predominantly pseudostratified in plateau-phase
      cultures. Based on experiments measuring the percentage of secretory cells and
      the amount of mucous secretion, development of the secretory cell phenotype was
      delayed in the absence of exogenous matrix but reached similar levels of
      secretory differentiation by day 13 of culture. In contrast, the development of
      ciliated cells was markedly reduced on uncoated membranes. These data suggest
      that although plating cells on type I collagen gel enhances cell attachment and
      accelerates the onset of secretory differentiation, type I collagen gel seems to
      be more critical for ciliated cell differentiation than for secretory cell
      differentiation.

PMID- 8534483
TI  - Expression of RANTES by human bronchial epithelial cells in vitro and in vivo and
      the effect of corticosteroids.
AB  - Recent studies have demonstrated that RANTES, a member of the CC chemokine family
      affecting monocytes, T cells, basophils, and eosinophils, is expressed by several
      cell types. To investigate whether human bronchial epithelial cells can also
      express this chemokine, we investigated human bronchial epithelial cells for
      their ability to synthesize RANTES, both in vitro and in vivo. Additionally, we
      investigated the effect of treatment for 4 mo with inhaled corticosteroids on the
      expression of RANTES in these cells in vivo. Human bronchial epithelial cells
      cultured from surgical tissue expressed the mRNA for RANTES and synthesized
      RANTES, as demonstrated by polymerase chain reaction and immunocytochemical
      staining and enzyme-linked immunosorbent assay, respectively. Incubation of the
      cultures with 50 ng/ml of tumor necrosis factor-alpha (TNF-alpha) significantly
      increased the release of RANTES into culture medium after 18 to 48 h of
      incubation, an effect that was abolished by treatment of the cultures with anti
      TNF-alpha antibody. RANTES was also expressed in the bronchial epithelium in
      vivo, as indicated by positive immunocytochemical staining of bronchial biopsy
      tissues obtained from mild asthmatic patients before and after treatment with 500
      micrograms of inhaled beclomethasone dipropionate (BDP) twice daily or matched
      placebo for 4 mo. Quantitation, by color image analysis, of the percentage of
      epithelium staining for RANTES showed that treatment with BDP decreased the
      expression of RANTES in the bronchial epithelium from 17.12% to 4.22% (P < 0.05).
      The numbers of EG2-staining cells in the epithelium were also reduced, from
      790.1/mm2 to 203.3/mm2 (geometric mean; P < 0.01), after BDP treatment. These
      results suggest that human bronchial epithelial cells are capable of synthesizing
      RANTES and may therefore play an important role in the development of
      inflammation in allergic airways disease. Furthermore, corticosteroids may
      prevent airway inflammation by downregulating the expression of proinflammatory
      cytokines in the bronchial epithelium.

PMID- 8534484
TI  - Production of interleukin-4 and interferon-gamma by TCR-V beta-expressing T-cell
      subsets in allergen-sensitized mice.
AB  - Sensitization of BALB/c mice to ovalbumin (OVA) through the airways stimulated
      allergen-specific immediate hypersensitivity responses and these effects were
      related to the expansion of V beta 8.1/8.2+ T cells. In contrast, splenic V beta
      2+ T cells from sensitized animals inhibited V beta 8.1/8.2+ T-cell induction of
      anti-OVA IgE production in vivo. To examine whether such differences in T-cell
      function were associated with differences in cytokine production, CD4+ T cells
      and CD4+ T cells depleted of V beta 8.1/8.2+ T cells were analyzed for
      interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production. In
      nonsensitized animals, no differences in IL-4 and IFN-gamma production were found
      in mRNA levels as well as in protein levels in these two populations of cells. In
      contrast, CD4+ T cells from sensitized mice showed higher IL-4 and lower IFN
      gamma production than CD4+ cells depleted of V beta 8+ lymphocytes. Similar
      results were obtained after stimulation of CD4+ T cells from OVA-sensitized
      animals with anti-V beta 2 and anti-V beta 8.1/8.2 antibodies. Stimulation of V
      beta 8.1/8.2+ T cells from sensitized mice with OVA or OVA peptide 323-339 also
      resulted in increased production of IL-4. These data indicate that allergen
      sensitization via the airways stimulates the selective expansion of certain V
      beta-expressing T cells and that these T-cell subsets exhibit different
      functional activities in terms of cytokine production.

PMID- 8534485
TI  - Functional regulation of beta 1 integrins on human eosinophils by divalent
      cations and cytokines.
AB  - Divalent cations and various soluble stimuli can alter cell adherence by
      affecting the avidity of adhesion molecules. We hypothesized that beta 1 integrin
      function of human eosinophils may be altered by divalent cations and eosinophil
      activating cytokines such as interleukin-5 (IL-5). Expression of the beta 1
      integrin activation epitope recognized by monoclonal antibody (mAb) 15/7 was
      evaluated by flow cytometry using purified eosinophils from allergic subjects,
      normal subjects, and late-phase bronchoalveolar lavage (BAL) fluids. Rapid and
      reversible 15/7 binding on eosinophils from each source was induced in Mn2+ (0.01
      1 mM) but not in buffers containing other divalent cations and occurred without
      affecting the total level of beta 1 integrin expression (quantified using mAb
      33B6). Augmentation of eosinophil adhesion to immobilized vascular cell adhesion
      molecule (VCAM-1) in Mn2+ followed a similar concentration dependence as mAb 15/7
      binding. Net binding to VCAM-1 in Mn2+ was completely inhibited with a mixture of
      alpha 4 and beta 1 integrin mAb while beta 2 integrin mAb had no effect. Exposure
      of eosinophils from allergic subjects to as little as 1 pg/ml IL-5 completely
      inhibited mAb 15/7 binding induced by Mn2+. In contrast, increased binding of mAb
      15/7 in Mn2+ was not blocked by IL-5 in eosinophils from normal subjects. For
      eosinophils from allergic subjects, IL-5 also inhibited Mn(2+)-induced adhesion
      to VCAM-1. Thus, beta 1 integrins on eosinophils from allergic and nonallergic
      subjects are modulated differently by Mn2+ and IL-5. Altered beta 1 integrin
      avidity may be one mechanism involved in preferential eosinophil recruitment in
      vivo.

PMID- 8534486
TI  - The role of fibrin degradation products in neutrophil recruitment to the lung.
AB  - Pulmonary epithelial injury leads to increased permeability and plasma exudation.
      Plasma rapidly forms an insoluble fibrin clot in the distal airspace because of
      the potent procoagulant activity expressed there. Because these airspaces also
      express potent fibrinolytic activity, digestion of fibrin results in high local
      concentrations of fibrin degradation products (FDP), which are biologically
      important molecules with numerous proinflammatory actions. Inflammatory lung
      injury is associated with neutrophil accumulation, and other matrix proteins
      affect inflammatory cell traffic. In this study we examined the potential role of
      FDP in neutrophil recruitment to the lung. Using a chemotaxis assay, we found
      that FDP are potent chemotactic proteins when neutrophils are prestimulated with
      lipopolysaccharide (LPS) or formylmethionylleucylphenylalanine (fMLP). Although
      FDP are high molecular weight proteins, we found that these potent
      chemoattractants induce polymorphonuclear leukocyte (PMN) migration across
      epithelial monolayers. The magnitude of response is dependent upon the
      monolayers' ability to form and maintain tight junctions. Human neutrophil
      elastase (HNE), another fibrinolytic enzyme released from neutrophils, digests
      fibrin into chemotactic peptides which are more potent on a weight basis than
      plasmin-generated FDP. Furthermore, HNE secondarily digests plasmin FDP,
      producing molecules which are more potent chemoattractants than native plasmin
      FDP. These observations suggest a potential mechanism whereby FDP may contribute
      to the neutrophil accumulation which characterizes many inflammatory lung
      diseases.

PMID- 8534487
TI  - Cellular localization of messenger RNAs for insulin-like growth factors (IGFs),
      their receptors and binding proteins during fetal rat lung development.
AB  - To gain insight into the role of the insulin-like growth factors (IGFs) in
      regulating lung development, we have used in situ hybridization histochemistry
      (ISHH) to examine the ontogeny and sites of expression of IGF-I and IGF-II, IGF
      binding proteins (IGFBP-1 to IGFBP-6), and IGF cell surface receptors in fetal
      rat lung from 15 to 21 days of gestation. Both IGF-I and IGF-II mRNAs were
      expressed throughout the developmental period studied with little change in
      apparent abundance. IGF-I mRNA localized to mesenchymal cells, especially those
      surrounding airway epithelium, while IGF-II mRNA, which was somewhat more
      abundant, localized predominantly to epithelia. The type 1 IGF receptor, the
      receptor that likely mediates the actions of both IGFs, was expressed widely in
      virtually all cells, whereas the expression of the type 2 IGF receptor, thought
      to be involved in IGF internalization and degradation, was confined to the
      mesenchyme and medial layers of intrapulmonary vessels. As with the IGFs, there
      was little apparent change in the abundance of IGF receptor mRNAs through fetal
      development, and the type 2 IGF receptor mRNA was more abundant. The expression
      of IGFBPs changed significantly during lung development. IGFBP-2, -3, -4, and -5
      were expressed from day 15 of gestation, but their sites of expression and
      ontogeny differed. IGFBP-2 mRNA expression was abundant and constant throughout
      gestation and was confined to proximal and distal airway epithelia. IGFBP-3 and
      IGFBP-5 also were expressed by proximal airway epithelia, but also exhibited
      significant expression in interstitial mesenchyme and in mesenchyme surrounding
      vessels. The abundance of both increased as gestation progressed (IGFBP-5 greater
      than IGFBP-3). IGFBP-4 mRNA was confined to interstitial mesenchyme and its
      abundance peaked at days 16 to 19 of gestation. We found no evidence for
      expression of either IGFBP-1 or IGFBP-6. We conclude that the expression of IGF
      I, IGF-II, and the type 1 IGF receptor throughout gestation in the lung supports
      a role for the IGFs in lung growth and development. The complex pattern of IGFBP
      expression (differing sites and ontogeny of expression) suggests that the IGFBPs
      modulate IGF actions at specific target sites. Furthermore, because there is
      little change in the expression of IGFs or IGF receptor mRNAs during fetal lung
      development, regulation of IGFBP expression may be essential to the control of
      IGF actions during lung development.

PMID- 8534488
TI  - Ozone-induced alterations in glutathione in lung subcompartments of rats and
      monkeys.
AB  - The current studies were designed to test two hypotheses: (1) differences in
      steady-state reduced glutathione levels are responsible for subcompartment
      differences in susceptibility to acute ozone injury, and (2) elevation of reduced
      glutathione concentrations accounts for the tolerance to further injury produced
      by repeated ozone exposure. Glutathione was measured in well-defined
      subcompartments of the lung of both rats and monkeys to compare alterations
      occurring in both target (distal trachea and terminal bronchiole) and nontarget
      areas (lobar bronchus, major daughter, minor daughter bronchus, and parenchyma)
      of the lung in species that differ in sensitivity to ozone exposure (rat is less
      susceptible than monkey). Glutathione concentrations were decreased in trachea of
      rats exposed to 0.4 ppm ozone for 2 h and increased in lobar bronchus and distal
      bronchiole after 2 h exposure at 1 ppm. In monkey, glutathione levels in most
      subcompartments were not altered by either 0.4 or 1.0 ppm ozone exposure for 2 h.
      The exceptions were the major daughter subcompartment (200% of control at 0.4 ppm
      exposure) and the distal bronchiole (55% of control at 1 ppm exposure). Ninety
      day ozone exposures (6 h/day x 5 days/week) in rats produced an elevation in
      glutathione (164% of control value) only in distal bronchiole at the 1 ppm
      exposure level. In a similar manner, glutathione levels in the distal bronchiole
      of monkeys exposed for 90 days to 1 ppm O3 were 165% of the corresponding control
      values. These results suggest the following: glutathione levels in target and
      nontarget areas of the lung and in susceptible versus less susceptible species
      are not the primary determinant in the differences observed in ozone toxicity;
      the response of lung subcompartments to short-term ozone exposure varied
      depending on airway subcompartment and species; increased glutathione levels may
      be one reason for adaptation of some airway epithelial cells from rats and
      monkeys exposed to O3 for long periods; and use of well-defined segments of the
      lung provides a means of assessing changes in target areas of the lung without
      dilution from nontarget areas.

PMID- 8534489
TI  - Nitrogen dioxide exposure increases airway contractile response to histamine by
      decreasing histamine N-methyltransferase activity in guinea pigs.
AB  - To determine the mechanism responsible for nitrogen dioxide (NO2)-induced airway
      hyperresponsiveness, we examined the effects of NO2 exposure on the contractile
      response to histamine and the level of histamine N-methyltransferase (HMT)
      activity, a histamine-degrading enzyme, in guinea pig trachea in vitro. Guinea
      pigs were divided into seven groups. Each group received continuous NO2 exposure
      (2.0 ppm) for either 2, 6, 12, 24, 48, or 96 h. The remaining group did not
      receive NO2 exposure (control). HMT activity in trachea was decreased from the
      control value of 70.3 +/- 7.7 pmol/min/mg protein to 34.6 +/- 6.7 pmol/min/mg
      protein by 12 h exposures of NO2. However, 24 and 48 h exposures of NO2 did not
      significantly alter HMT activity. In contrast, HMT activity exceeded the control
      value by 96 h exposures of NO2 (85.5 +/- 5.1 pmol/min/mg protein). Twelve hour
      exposures of NO2 shifted the concentration-response curves to histamine to lower
      concentrations and significantly reduced the median effective concentration
      (EC50) of histamine (log M) from the control value of -5.16 +/- 0.09 to -6.15 +/-
      0.14 (P < 0.01). In contrast, the EC50 concentration of histamine (log M)
      increased from the control value of -5.20 +/- 0.10 to -4.90 +/- 0.11 by 96 h
      exposures of NO2 (P < 0.05). However, NO2 exposure did not alter the contractile
      response to acetylcholine. Morphologically, tracheal epithelial cells had
      vacuoles after 12 h exposures of NO2, but denudation of the epithelium did not
      occur during this experiment. In situ hybridization for HMT mRNA demonstrated
      that the level of HMT mRNA increased dominantly in tracheal epithelial cells
      after 96 h exposures of NO2. The present results indicated that the decrease in
      the level of HMT activity in the trachea was closely associated with the increase
      in the airway contractile response to histamine, suggesting that NO2-induced
      transient airway hyperresponsiveness to histamine is due to the decreased
      capacity of histamine catabolism in airway.

PMID- 8534490
TI  - Role of interleukin-4 and vascular cell adhesion molecule-1 in selective
      eosinophil migration into the airways in allergic asthma.
AB  - Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved
      in the preferential migration of eosinophils into the airways in allergic asthma
      through its capacity to selectively increase vascular cell adhesion molecule-1
      (VCAM-1) expression on vessels. To test this hypothesis, we studied the
      expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1)
      on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics
      using an immunohistochemistry technique and related the observations to IL-4
      levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to
      eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid
      from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid)
      (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4
      negative asthmatics). The IL-4-positive asthmatics showed a significantly
      increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as
      compared with both IL-4-negative asthmatics (P < 0.001) and diseased control
      subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated
      with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant
      correlation between the endothelial expression of VCAM-1 and the number of
      eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P <
      0.001). A significant correlation was also found between BAL IL-4 levels and the
      number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective
      activator also in human airways and the VCAM-1-dependent pathways play a role in
      selective migration of eosinophils into the airways in allergic asthma, and
      support the hypothesis described above.

PMID- 8534491
TI  - Effects of integrin clustering on human lung mast cells and basophils.
AB  - The interaction of cells with the extracellular matrix can alter cell responses
      and is regulated by integrins on the cell surface. We used monoclonal antibodies
      to the VLA-4 integrins CD29 and CD49d followed by an F(ab')2 fragment of rabbit
      anti-mouse immunoglobulin G1 to crosslink integrins on the surface of human lung
      mast cells and basophils. Crosslinking either CD29 or CD49d caused a significant
      histamine release (HR) from the basophils of most asthmatic donors (10 of 14 for
      CD49d and 7 of 10 for CD29) (HR = 21 +/- 5%, n = 10, P < 0.005 for CD29 and HR =
      19 +/- 4%, n = 14, P < 0.01 for CD49d) yet failed to initiate HR from the
      basophils of non-atopic and atopic donors (HR was 1 +/- 0.5% for CD29 and 1 +/-
      0.5% for CD49d, n = 10, P = NS). Crosslinking either CD29 or CD49d also failed to
      initiate histamine release from human lung mast cells (HR was 1 +/- 1% for CD29
      and 2 +/- 1% for CD49d). The basophils of asthmatic donors responded to 100 and
      30 micrograms/ml tissue fibronectin (HR = 12 +/- 2% and 10 +/- 3% for 100 and 30
      micrograms/ml fibronectin, respectively, n = 18, P < 0.05), whereas basophils of
      nonasthmatic patients again failed to degranulate (HR was 0 +/- 0.4% and 1 +/-
      0.6%, respectively, n = 11, P = NS). In contrast to the basophil, crosslinking of
      either CD29 or CD49d failed to initiate histamine release in human lung mast
      cells (HR = 1 +/- 1% for CD29 and 2 +/- 1%, n = 15). Human lung mast cells were
      also unresponsive to tissue fibronectin (100 and 30 micrograms/ml) (HR = 1 +/-
      1%, n = 5). The tyrosine kinase inhibitor, genistein, significantly reduced CD29-
      and CD49d-induced HR (inhibition = 83 +/- 7% for CD29 and 77 +/- 6% for CD49d, n
      > or = 5, P < 0.05). A second tyrosine kinase inhibitor, piceatannol, also
      significantly reduced both CD29- and CD49d-induced HR (inhibition was 62 +/- 19%
      for CD29 and 56 +/- 14% for CD49d, n = 7, P < or = 0.05). Integrin crosslinking
      also affected the response to a second, immunoglobulin E (IgE)-dependent
      stimulus. Both CD29 and CD49d clustering significantly inhibited anti-IgE-induced
      histamine release from the human basophil. Inhibition was 30 +/- 5%, n = 18, P <
      or = 0.001 for CD29 versus 40 +/- 6% for CD49d. In summary, we have shown that
      crosslinking the beta 1 integrins using either monoclonal antibodies or tissue
      fibronectin can initiate mediator release from the basophils of asthmatic
      patients by a mechanism which appears to be tyrosine kinase-mediated. In
      addition, clustering of integrins modulates the response to a second IgE
      dependent signal.

PMID- 8534492
TI  - Cardiac MR imaging: principles and techniques.
AB  - Magnetic resonance (MR) imaging is becoming an important tool in diagnosing
      cardiovascular disease. Many technical advances have contributed to the improved
      capability of MR imaging in this arena. In this article, we review the technical
      concepts and recent advances for a variety of cardiovascular applications,
      including evaluation of congenital heart and great vessel disease, global cardiac
      function using cine acquisitions and automated ventricular volume segmentation,
      valvular heart disease, myocardial wall motion detection with magnetization
      tagging, two-dimensional and three-dimensional coronary artery imaging, and
      myocardial perfusion. Sequence diagrams are shown and important technical issues
      are discussed. Example images are shown to demonstrate the current status of
      research and future potential. Most results shown here are high-resolution scans
      acquired with new gradient coil systems, including coronary artery imaging using
      an in-plane resolution of 350 microns x 600 microns. This review serves as an
      introduction to the discussion of various clinical applications of cardiovascular
      MR imaging provided in this issue.

PMID- 8534493
TI  - MR evaluation of myocardial ischemia and infarction.
AB  - Magnetic resonance (MR) imaging is potentially a well-suited modality to guide
      clinical management of patients with myocardial ischemia and infarction.
      Evaluation of regional perfusion and contractile function distinguishes between
      normal and ischemic myocardium and identifies areas of infarction, stunning, and
      hibernation. Recent technical improvements in MR perfusion imaging include the
      use of echoplanar and fast gradient-echo sequences to capture the first pass of
      MR contrast agents through the myocardium. Evaluation of regional function will
      likely benefit from motion-encoded MR imaging, which employs tissue tagging or
      cine phase-contrast to track the myocardial motion throughout the cardiac cycle.
      Stress imaging with dobutamine and dipyridamole will further enhance the accuracy
      of MR myocardial imaging. Advantages of MR imaging over other available
      noninvasive modalities include its good spatial resolution and the potential for
      three-dimensional imaging without the need for geometric assumptions.
      Importantly, a single comprehensive MR examination can assess not only regional
      myocardial perfusion and function, but in addition also global ventricular size
      and function and (perhaps) coronary artery anatomy and flow. Such integrated
      cardiac evaluation may turn out to be a cost-effective strategy. Large clinical
      trials incorporating outcome analysis are now needed to see whether cardiac MR
      imaging can live up to the current high expectations.

PMID- 8534494
TI  - MR evaluation of cardiac/juxtacardiac masses.
AB  - With its superb contrast resolution, multiplanar imaging capability, and large
      field of view, magnetic resonance imaging is the gold standard in the imaging
      evaluation of cardiac and juxtacardiac masses. Spin echo images graphically
      display the pathoanatomy of intracavitary, valvular, myocardial, pericardial, and
      juxtacardial masses. Dynamic imaging techniques are used to identify their
      pathophysiologic consequences on myocardial contraction dynamics, valvular
      function, or blood flow mechanics. Echocardiography is a good modality to
      evaluate the heart and in most institutions, remains the initial test in the
      workup of cardiac masses. However, equivocal echocardiographic studies are common
      and, in fact, are the leading indication for the use of MR in the workup of
      cardiac/juxtacardiac masses.

PMID- 8534495
TI  - Magnetic resonance imaging of congenital heart disease.
AB  - Magnetic resonance imaging plays a very important role in the noninvasive
      evaluation of patients with congenital heart defects. The purpose of this article
      is to address the practical application of this technology to patients with
      congenital heart defects. Issues related to patient monitoring, image
      interpretation, and specific applications in different disease entities are also
      discussed.

PMID- 8534496
TI  - MR evaluation of the pericardium.
AB  - The pericardium is well visualized on magnetic resonance imaging (MRI) because of
      the superb contrast resolution and multiplanar capability of the technique. This
      article highlights some of the clinical uses of MRI in evaluating the pericardium
      and provides comparison with echocardiography and computed tomography (CT) scan.
      Specific pericardial diseases that are described include pericardial effusion,
      constrictive pericarditis, neoplastic pericardial disease, congenital
      abnormalities of the pericardium, and paracardiac masses. The value of MRI in
      differentiating constrictive pericarditis from restrictive cardiomyopathy is
      emphasized. The article discusses the impact of newer MRI techniques such as cine
      MRI on the assessment of pericardial disease.

PMID- 8534497
TI  - MR angiography of the coronary arteries.
AB  - Magnetic resonance angiography (MRA) of the coronary arteries has recently become
      possible due to the development of a new group of ultrafast imaging sequences.
      Coronary arteries are small, tortuous vessels subjected to significant
      physiological motions (respiration and cardiac contractions). Most coronary MRA
      pulse sequences rely on a combination of segmental acquisition of data (in k
      space) to minimize cardiac motion artifacts and patient breath-holding to
      minimize respiratory motion artifacts. MR is noninvasive, does not require any
      contrast agents or ionizing radiation, and thus offers the potential of becoming
      a very important cardiac screening tool. Coronary MRA can routinely depict the
      proximal and middle portion of most coronary arteries and some coronary artery
      branches. However, its clinical utility for detecting lesions has not yet been
      proven. As coronary MRA techniques improve they may become an integral part of
      the evaluation of patients with ischemic heart disease. Existing coronary MRA
      techniques can already play a significant clinical role in the evaluation of
      coronary artery anomalies, in the follow-up of proximal lesions after
      angioplasty, and in the noninvasive determination of patency of bypass grafts and
      coronary stents.

PMID- 8534498
TI  - Immunogenetic Risk Assessment in Human Disease. Proceedings of a symposium.
      Charleston, South Carolina, March 6-8, 1994.

PMID- 8534499
TI  - Spontaneous mutation as a risk factor.
AB  - From various estimates of the mutation rate per nucleotide per generation,
      centering around 1-2 x 10(-8) and the number of nucleotide pairs, 3 x 10(9) per
      genome, the number of new mutations in a human zygote is very large, in the order
      of 100. The mutation rate is an order of magnitude higher in males than females,
      due presumably to the greater number of cell divisions in the male germ line, and
      increases more than linearly with paternal age. It is likely that a large
      fraction of these mutations are in unimportant 'junk' DNA, but if even 2% of the
      mutations are selected, this means two new deleterious mutations per generation.
      It is suggested that quasi-truncation selection is the most likely way in which
      this large number of mutations can be eliminated from the population without an
      excessive burden of reduced viability and fertility.

PMID- 8534500
TI  - Linkage and association to genetic markers.
AB  - Genetic markers that are sufficiently polymorphic (as measured by their
      heterozygosities) can be used in linkage and association analyses to detect
      Mendelian segregation underlying disease phenotypes. Each type of analysis can
      either be based on a specific genetic model or not make any assumptions about the
      mode of inheritance of the disease. Principles underlying these methods are
      reviewed, and the assumptions underlying them stressed. Association analyses are
      more powerful, provided there is linkage disequilibrium between the marker and
      disease loci; however, only linkage analyses have power in the absence of such
      disequilibrium. For this reason, models that allow for both kinds of tests are
      preferred, and such models must adequately approximate the complexity of the
      disease being studied.

PMID- 8534501
TI  - Major gene analysis for diseases and disorders of complex etiology.
AB  - Genetic analysis of complex diseases is undergoing a paradigm shift as the DNA
      technology and computational resources for analysis become more precise. In this
      review we compare the old paradigm for genetic disease analysis with the new,
      more powerful and efficient methods, which rely on the application of genetically
      linked markers. To illustrate the utility of the new approach, we apply it in the
      study of ankylosing spondylitis.

PMID- 8534502
TI  - Advances in HLA genetics.
AB  - The major histocompatibility complex (MHC) is a genetic system of over 70 known
      genes that occupies the midportion of the short arm of the sixth chromosome (C6p)
      and spans about 4 million base pairs of DNA. The high-resolution typing of class
      I and class II MHC genes and the identification of genes between and near them
      has increased the definition of the genetic basis of immune responses and
      diseases of unknown etiology such as autoimmune diseases in man. Although there
      are many more genetic systems that participate in the rejection of tissues and in
      the immune response, the MHC plays a central role in tissue compatibility and
      immune response against cancer and infectious diseases. In this paper, the
      authors review evidence about the role of HLA polymorphism in the pathogenesis
      and development of cancer, infectious diseases, autoimmune diseases and
      transplantation.

PMID- 8534503
TI  - The human immune response to hepatitis B surface antigen.
AB  - The anti-HBs response is bimodal with 4.2% of healthy persons producing no
      antibody and an additional 10% being hyporesponders. In the study of
      nonresponders, 2 extended haplotypes, [HLA-B8, SC01, DR3] and [HLA-B44, FC31,
      DR7], were found to be enriched in a pattern suggesting recessive inheritance. In
      the prospective immunization of homozygotes and heterozygotes for [HLA-B8, SC01,
      DR3], the homozygotes had less antibody than the heterozygotes. Family studies
      confirmed that the anti-HBs response was dominant and MHC linked, whereas
      nonresponse was recessive. In studies in vitro, it was shown that nonresponders
      failed to show lymphoproliferation in response to hepatitis B surface antigen
      (HBsAg) or an immunodominant nonapeptide. The lymphoproliferative response of
      responders to these stimuli was comparable and inhibited by anti-DR but not
      antibody to DQ or DP. The removal of CD8+ T cells did not produce
      lymphoproliferation to HBsAg in nonresponders. From mixtures of antigen
      presenting cells and T cells from MHC-identical response discordant pairs, it was
      shown that the defect in the nonresponders was in their T cells and not their
      antigen-presenting cells, ruling out defective MHC binding or antigen processing
      as the basis of nonresponse.

PMID- 8534504
TI  - Genetics of autoimmune diseases.
AB  - Many lines of evidence suggest that autoimmune diseases are the result of chronic
      immune activation in genetically susceptible individuals following specific
      environmental exposures. Although the rarity and heterogeneity of autoimmune
      diseases and the lack of understanding of pathogenetic mechanisms have inhibited
      progress in the field, genes encoding histocompatibility molecules,
      immunoglobulins, complement components, peptide transporter proteins, T-cell
      receptors, sex hormones, cytokines, and metabolic enzymes important in drug and
      toxin elimination, have been identified as risk factors for one or more
      autoimmune diseases. Novel molecular genetic techniques and epidemiologic
      approaches that subset diseases by demographics, clinical manifestations,
      serology, and environmental exposures, should further elucidate the environmental
      and genetic risk factors for these increasingly recognized multifactorial
      disorders.

PMID- 8534505
TI  - Advances in human immunoglobulin allotypes.
AB  - Monoclonal anti-Rh's and monoclonal anti-Gm's are now available, permitting a
      more precise serological determination of the human allotypes. Several Gm
      allotypes can be determined at the gene level, without resort to serological
      reagents. PCR, subclass-specific amplification and allele-specific probes are
      used. Many RFLPs of the human IgH C- and V-region genes have now been defined.
      More than 10(6) variant haplotypes of the so-called constant part of the Ig chain
      are possible because more than 20 polymorphic sites are known. A schematic
      physical map of the human IgHC gene cluster is presented.

PMID- 8534506
TI  - Immunoglobulin allotypes and RFLPs in disease association.
AB  - Immunoglobulin heavy chain (Gm) and light chain (Km) allotypes have been
      extensively studied as possible markers of susceptibility to a range of immune
      related diseases including malignancies, infectious diseases and autoimmune
      disorders. This review is concentrated on susceptibility to multiple sclerosis,
      systemic lupus erythematosus and insulin-dependent diabetes mellitus.

PMID- 8534507
TI  - HLA, Gm, and Km polymorphisms and immunity to infectious diseases in South
      Amerinds.
AB  - Isolated South Amerinds, a population at very high risk from infectious disease,
      mount good immune responses to pneumococcal polysaccharides, viral antigens and
      other immunogens. No unusual immunoglobulin allotype or HLA antigen, which might
      explain the high risk from infectious disease, was found among them. Responses
      are examined in relation to the immunogenetic markers that are most prevalent.
      Amerinds with Gm 1,2,17,21 responded less well than persons without this
      haplotype to 10 of 12 pneumococcal polysaccharides, and those who were homozygous
      at the HLA class I loci responded less well to viral antigens. However, these
      differences are not strong and there are few such findings relative to the number
      of possibilities examined. The most distinctive immunogenetic characteristic of
      these populations is their low level of polymorphism at all tested loci. Their
      susceptibility to infectious agents can be attributed to this genetic uniformity
      and a consequent ability of pathogens to adapt to the population.

PMID- 8534508
TI  - Perspectives and future directions. Immunogenetics.
AB  - An outline of the history of immunogenetics is presented. The usefulness of the
      Rh, HLA and Gm systems in disease prediction and prevention will increase with
      our capacity precisely to relate polymorphic variants to particular functions and
      pathophysiological events. Alloimmunization to Gm markers is common in rheumatoid
      arthritis, an allegedly autoimmune disease. This paradox and the paradox of
      nonnominal allotypes, disobeying Mendelian rules, are resolved by the
      interpretation that herpesviruses may transfer nonself polymorphic genes.
      Transduction of such genes may be important also in AIDS pathogenesis.

PMID- 8534509
TI  - [Recent advances in Fukuyama type congenital muscular dystrophy].
AB  - There have been numerous reports as well as case presentations, in the field of
      clinical research since Fukuyama type congenital muscular dystrophy (FCMD) was
      first reported by Fukuyama et al. as a peculiar form of congenital progressive
      muscular dystrophy (CMD). Toda et al. localized the FCMD gene locus to chromosome
      9q31-33 using genetic linkage analysis. Clinical application of molecular genetic
      studies is a new and exciting aspect of FCMD research. The author reviewed the
      literature and discusses herein: [1] the classification of CMD and the position
      of FCMD, [2] researches on the pathogenesis and pathophysiology of FCMD, [3] DNA
      diagnosis using polymorphism analysis (carrier diagnosis and prenatal diagnosis),
      [4] approaches to clinical heterogeneity in FCMD, [5] the difference between FCMD
      and Walker-Warburg syndrome. In addition, data accumulated by the authors are
      presented.

PMID- 8534510
TI  - [Clinical studies of learning disability. Part I: Two-axial diagnosis of learning
      disability using the Pupil Rating Scale Revised (PRS) and WISC-R].
AB  - We investigated the correlation between intelligence quotient and school
      performance evaluated by PRS (the Pupil Rating Scale Revised) to assess an
      adequacy of two-axial diagnosis of learning disabilities (LD). The subjects were
      37 children, including 31 cases with developmental or school problems and 6
      normal children. The Japanese Wechsler Intelligence Scale for Children-Revised
      (WISC-R) was employed for an estimation of intelligence quotient (IQ) and, PRS
      was used to evaluate school performance. We defined 'LD risk child' as a child
      whose IQ was no less than 70 and PRS score was no more than 65. A statistical
      evaluation of IQ and PRS was done in this group separately. Ten children were
      diagnosed as 'LD risk' using this criterion. Fourteen children had normal IQ, and
      thirteen children were mentally retarded. There was a significant correlation (r
      = 0.68, P < 0.001) between IQ and the PRS score in these 37 children. On the
      other hand, no significant correlation was found between IQ and the PRS score of
      the 'LD risk child'. This result suggests that we can expect high PRS score in
      proportion to their IQ level. Because LD children generally tend to demonstrate
      deviated IQ-school performance correlation, we conclude that the WISC-R and PRS
      are appropriate for two-axial screening of LD.

PMID- 8534511
TI  - [Clinical studies of learning disability. Part II: A prospective study of
      children with risk factors for learning disability at three year-old screening].
AB  - We followed children with the risk factors for learning disability (LD) at the
      three year-old screening prospectively. The five risk factors were speech delay,
      hyperkinesia, delayed social skill, delayed comparative conception (big and
      small, long and short) and mutistic behaviour. We evaluated seventeen elementary
      school children using WISC-R and the Pupil Rating Scale Revised. Six of them were
      diagnosed as normal, six were learning-disabled, and five were mentally retarded
      children. We proposed that the screening of LD at three years by the risk factors
      were effective but only partially.

PMID- 8534512
TI  - [A clinical study of sudden death in the severely handicapped persons].
AB  - A clinical study was performed on 8 cases of sudden death (9.0%) selected from a
      series of 89 patients with severe handicaps who died at the Metropolitan Medical
      Center of Severely Handicapped during the period from 1968 through 1986. 1) All
      suffered from profound mental retardation with motor disturbance, but were able
      to react to environmental stimuli. 2) Most had mixed quadriplegia showing
      athetosis-related hypertonus. 3) Severe physical deformation and chronic
      respiratory symptoms were present in 6 of 8 patients. 4) Most of them were
      adolescent. 5) Autopsy revealed no particular findings to which the expected
      death could be attributed except for the right cardiac enlargement in 5 cases.
      Four of the 8 patients were recovering from respiratory infection or were in the
      process of having their anticonvulsant doses tapered. These four cases had shown
      recent improvement in their general systemic condition. Sudden death occurred
      mainly during limited time periods in the early morning or in the evening and was
      not related to sleep. The authors suggest that the changes in the autonomic
      nervous system may precipitate them into sudden death.

PMID- 8534513
TI  - [Sisters with early onset hereditary dentatorubral-pallidoluysian atrophy of
      childhood--DNA analysis and clinicopathological findings].
AB  - Two sisters were presented, 16 years old and 12 years old, who showed similar
      clinical courses. They had had mental retardation since early childhood, and then
      ataxia began. They suffered from astatic and tonic seizures from early school
      age, which gradually evolved to intractable epilepsies. Spasticity progressed,
      and they deteriorated both physically and mentally. They revealed photo
      sensitivity; convulsions were induced by the flickering of light. They were
      attacked by myoclonic seizures as well as choreoathetosis, and became bedridden
      by the latter part of the elementary school age. There were no fruitful results
      of any kind from the laboratory examinations for metabolic disorders. EEG showed
      that the epileptic seizure discharges were induced by photic stimulation; there
      were frequent 3-4 Hz diffuse spike-and-wave short bursts during waking and sleep
      periods. MRI findings of the elder sister at the age of 16 revealed remarkable
      diffuse brain atrophy. Gene analysis showed abnormally enlarged DNA fragments
      localized on the short arm of chromosome 12. This meant expanded CAG
      trinucleotide repeats. The younger sister died at the age of 12 years. Autopsy
      findings revealed degeneration of both dentatorubral and pallidoluysian pathways.
      There were especially remarkable gliosis and neuronal cell loss in the outer
      segment of globus pallidus, and moderate neuronal cell loss and typical grumose
      degeneration in the dentate nucleus. The diagnosis of juvenile-type hereditary
      dentatorubral-pallidoluysian atrophy was compatible with the pathologic findings.
      This diagnosis will be made possible before death through the understanding of
      the clinical symptoms and molecular genetics.

PMID- 8534514
TI  - [The effect of early treatment for children with cerebral palsy in cooperation
      with city health welfare offices].
AB  - The Yokohama Rehabilitation Center has been treating children with cerebral palsy
      mainly by Vojta's method. We divided 90 cases with cerebral-palsied patients into
      two groups according to the month when the treatment started. The first group
      consisted of 27 cases started treatment before six months old; the second group
      consisted of 63 cases, after seven months old. Of these, all eleven children with
      hemiparetic type learned walking. Forty-one children with tetraparesis, spastic
      or mixed type could not learn walking. In the other types of cerebral palsy,
      84.6% of the first group, and 40.0% of the second group could walk eventually.
      Though all cases in the first group had perinatal disturbances, 11 cases (17.5%)
      in the second group had none. The results of the treatment for the children with
      cerebral palsy of the first and second groups show that early treatment is
      effective and necessary. Developmental screening for four-month-old is performed
      at the city health welfare offices. This has a great role in finding risky babies
      of cerebral palsy. Risky babies checked at four months of age could have therapy
      at six months of age at the latest. So it is important to diagnose them as early
      as possible in cooperation with the city health welfare offices.

PMID- 8534515
TI  - [Reflex sympathetic dystrophy: a case report].
AB  - We described an 11-year-old boy with reflex sympathetic dystrophy (RSD). He
      presented symptoms of allodynia and hyperesthesia in the right foot with pale
      color and coldness. Before the onset he had abdominal pain and a change of taste.
      The symptoms were resistant to physical therapy and the right foot became
      atrophic. Intermittent lumber epidural anesthesia by an indwelling catheter was
      performed for three weeks after 5 months from the onset. Improvement of symptoms
      did not occur during the anesthesia, but did soon after that. The pathogenesis of
      RSD remains unknown, although a psychological factor may have been involved in
      this case. RSD in childhood is usually considered to be more responsive to
      conservative therapy. However, some children such as our patient are resistant to
      conservative therapy. Recognition of RSD and early interventions such as physical
      therapy and psychological approach are important. In intractable cases invasive
      approaches such as sympathetic blockade should be also considered.

PMID- 8534516
TI  - [Taste disturbance as an initial manifestation of Guillain-Barre syndrome in a 14
      year-old girl].
AB  - We reported a 14-year-old girl who showed taste disturbance as an initial
      manifestation of Guillain-Barre syndrome (GBS). After an upper respiratory
      infection, she initially complained of taste disturbance, diplopia and
      salivation, followed by weakness in the legs and numbness in the extremities. On
      admission, she showed taste deficiency for sweet and sour sense, and a decline of
      salty and bitter taste. Weakness in the legs and disappearance of deep tendon
      reflexes were also noticed. We considered that the findings of
      electrophysiological examinations would conform to demyelinating features.
      Laboratory examinations revealed an increase of memory T cells in the peripheral
      blood and an elevated level of myelin basic protein in the cerebrospinal fluid.
      Based on clinical features and laboratory data, the diagnosis of GBS was made. We
      should keep taste disturbance in mind as one of the signs of GBS.

PMID- 8534517
TI  - [A case of behavior disorder with gait and sleep disturbances induced by
      zonisamide].

PMID- 8534518
TI  - [Effectiveness of intravenous midazolam for the treatment of status epilepticus
      in a child with severe myoclonic epilepsy in infancy].

PMID- 8534519
TI  - [The effect of zonisamide in West syndrome].

PMID- 8534520
TI  - [Two cases of possible cerebrocerebellar lissencephaly variant of type I].

PMID- 8534521
TI  - Implications of middle ear hyperoxia induced by ventilation tubes in otitis media
      with effusion.

PMID- 8534522
TI  - Tissue distribution and tumor localization of effector cells in adoptive
      immunotherapy of cancer.
AB  - In adoptive immunotherapy (AIT) of cancer, lymphocytes are isolated from the
      patient's blood and activated in vitro by the cytokine interleukin-2 (IL-2). In
      response to the IL-2 the lymphocytes proliferate vigorously and their cytotoxic
      potential increases several fold. After 5-10 days in culture, the cells-now
      called lymphokine-activated killer (LAK) cells-are injected back into the patient
      together with IL-2. The many positive results from preclinical animal models
      justified the rapid transit of AIT into the clinic, but the clinical results have
      far from fulfilled expectations. Many cancer centers have concluded that AIT in
      its present configuration is not cost-effective given that the average response
      rate is as low as 20-30%. Since a significant group of patients has shown
      complete responses after AIT, the challenge is to elucidate the conditions
      leading to optimal efficacy of AIT. It is generally accepted that the
      antineoplastic effect of LAK cells requires a close contact between the LAK cells
      and tumor cells. A central question in analyses of the mechanisms behind AIT is
      the ability of the LAK cells to localize to the malignant tissues. The earliest
      studies of the tissue distribution of 51Cr- and 111In-labeled LAK cells indicated
      that LAK cells, upon intravenous (i.v.) injection, are initially retained in the
      lungs, but redistribute to liver and spleen during the following 16-24 hours.
      However, our studies of the traffic and fate of i.v. injected tumor cells have
      shown that the use of 51Cr and 111In as cell labels often results in an over
      estimation of the traffic of cells to liver and spleen and leads to falsely high
      predictions as to the survival of the injected cells, due to non-specific
      accumulation of 51Cr and 111In in liver and spleen after their release from dead
      cells. Use of 125IUdR, which does not accumulate in liver and spleen following
      release from dead cells, shows that the traffic of LAK cells into these organs
      was much lower than previously thought. These experiments have now been repeated
      using other cell labels (such as fluorescence dyes and immunohistochemistry) and
      they confirm that only few LAK cells redistribute from the lungs to the liver and
      spleen and that most die within the first 24 hours following injection. Thus, the
      circulatory potential of LAK cells is very low and chances that i.v. injected LAK
      cells will be able to localize into tumors and metastases located in other organs
      than the lungs, seems small. Indeed, while fluorescence-labeled LAK cells
      selectively localize into pulmonary metastases following intravenous injection,
      no infiltration of extrapulmonary metastases is seen. Furthermore, quantitative
      analyses have shown that even though the localization of LAK cells into pulmonary
      metastases is highly specific (5-10 fold higher numbers of LAK cells are often
      found in the metastases compared to the surrounding normal lung tissue), only 5%
      of the injected cells reach the malignant tissues. It is therefore reasonable to
      assume that the efficacy of AIT can be improved if the in vivo survival of the
      LAK cells can be prolonged and if their ability to infiltrate tumors regardless
      of their location, can be augmented. Previous studies in murine models have shown
      that i.v. injected tumor cells are sequestrated in the lungs and that only few of
      them reach other organs. However, when the tumor cells were injected into the
      left ventricle of the heart (bypassing the lung capillaries), significant numbers
      of tumor cells were found in the liver. It therefore seemed reasonable to
      speculate that LAK cells injected into the left ventricle of the heart or
      directly into the arteries supplying the tumor-bearing organ would have better
      chances of localizing to the malignant tissue. This seemed to be correct in that
      10 fold higher numbers of LAK cells were found in the liver following intraportal
      injection compared to intravenous injection.

PMID- 8534523
TI  - Multidisciplinarity and multimedia in quality of care--education.
AB  - Quality of care and quality of life are patient-centred, whereas medical
      education tends to be disease-centred. More patient-centred models will be
      necessary to optimise the quality of care for cancer patients. This demands new
      priorities in medical education, new concepts for structuring and organising
      responsibilities in medical care, and new complementary task definitions for the
      players involved. Goal setting and functional care models are conceptual
      innovations that can help introduce the patient-centred approach into medical
      practice. In the care of patients with cancer, the goals of the physician, nurse,
      patient, and family may change and diverge as the disease progresses,
      necessitating open discussion and bargaining. Functional care models stress that
      the quality of care can be defined differently at the four different levels of
      care--medical, nursing, cleaning/providing, and support from family and friends.
      Instruments that maintain the focus of care on the patient's quality of life can
      help formalise the goal-setting process. Quality of life measuring instruments
      should be adapted to the priorities of the clinical situation and implemented in
      basic practice routines. There is no single objective quality of life level or
      score, and measuring instruments must take into account different quality of life
      options. Multidisciplinarity and multimedia education means the appropriate
      learning instruments at the appropriate time for all those concerned.

PMID- 8534524
TI  - Using quality of life assessment methods in patients with advanced cancer: a
      clinical perspective.
AB  - The incidence of cancer is expected to increase in most European countries by at
      least 20-30% in the next two decades. This change in incidence, combined with
      probably small changes in cure rate, will call for an increased effort in
      palliative oncology. Most patients with advanced malignant diseases have various
      unpleasant symptoms which are inadequately treated. In assessing patients'
      symptoms and well being, health-related quality of life (HRQL) should be the
      primary endpoint. Several HRQL instruments have been found to be valid for use in
      cancer clinical trials. The EORTC QLQ-C30 is one among several cancer-specific
      HRQL instruments. The QLQ-C30 is composed of nine multi-item scales and six
      single item measures. This instrument is developed to be used in conjunction with
      disease and/or specific modules.

PMID- 8534525
TI  - A proposed matrix for organisational changes to improve quality of life in
      oncology.
AB  - Educational and institutional changes are needed to improve the care of dying
      patients. There are four phases to a cancer control programme, and each phase
      stresses prevention. The fourth phase of a cancer control programme is concerned
      with the prevention of suffering, through impeccable management of physical and
      psychosocial distress. In practice, cancer control is usually addressed primarily
      as a biological problem, with less emphasis placed on behavioural aspects and the
      alleviation of suffering. The principles of symptom control and the management of
      psychosocial issues have been defined by the palliative care movement. However,
      this body of knowledge tends to be cocooned within palliative care programmes and
      associated journals and textbooks. As exemplified by recent advances in cancer
      pain management, symptom control research is a promising area for development.
      However, the promise is not matched by priority assignment and idea
      implementation. This article offers proposals for specific changes in the
      structure of university and cancer programmes, and revision of legislative
      policies which will enhance the care of patients who depend upon our interest in
      the fourth phase of cancer control, the prevention and relief of suffering.

PMID- 8534526
TI  - Recent clinical trials of pain control: impact on quality of life.
AB  - The understanding and treatment of pain is one of the oldest challenges for
      physicians, scientists and philosophers. Much of our present rationale of pain
      control is based on the Cartesian idea that pain mostly originates from external
      or internal noxious stimuli, which are transmitted to and interpreted in the
      brain. Consequently, removal (blocking) of the stimuli and modification of
      cerebral awareness have been the prime targets of analgesic interventions. Only
      recently has the relationship between pain and other physical, psychological and
      social aspects of illness been considered in the overall management plan. Most of
      the literature on pain control reveals the physical bias of measurement. Apart
      from simple but reliable tools such as visual analogue scales and Likert-type
      verbal scales, more sophisticated measures such as multidimensional pain
      inventories have also been used when it is necessary to characterise pain more
      specifically. In clinical studies, it is usual to ask the patient to report on
      his own pain, although proxy measures such as mobility, performance status and
      analgesic consumption are also often used. The hospice concept of "total pain",
      in which the psychological, social, spiritual and other aspects are emphasised,
      has been influential in our new approach to pain measurement. Particularly when
      it is chronic and related to advancing disease as in metastatic cancer, pain can
      interact significantly with many facets of daily living. A holistic model of
      quality of life in such patients should, therefore, include a multidimensional or
      modular assessment of these areas. Medical interventions themselves can affect
      quality of life in both positive and negative ways. Some side-effects may be so
      common as to be accepted as "normal", e.g. constipation or sedation with opioids:
      it is only by their careful evaluation, when comparing opioids with essentially
      similar analgesic potentials, that differential toxicities may be revealed.
      Simple recording of physical side-effects of drugs is really not sufficient,
      because analgesics as well as other therapies may be associated with mood changes
      and broader consequences for quality of life. Only in the past few years has
      quality of life been seriously addressed in palliation research. For example,
      standardised quality of life scales are now included almost routinely in
      oncological studies involving radiotherapy or chemotherapy by the Medical
      Research Council (MRC) of Great Britain. Trials of the new biphosphonates, which
      can reduce bone pain in metastatic cancer, have been enhanced by incorporating
      quality of life measures. Based on the experience from earlier efficacy/safety
      studies with the new transdermal route of drug delivery for the opioid fentanyl,
      important areas of life such as sleep and cognitive function have been addressed.
      Randomised controlled trials of analgesics which include quality of life
      endpoints are still rare, but should be encouraged as these represent the most
      rigorous way of evaluating new therapies. The current preoccupation with quality
      assurance in healthcare is directed, ultimately, to the delivery of a better
      quality of care, which should also be more cost-effective, for large populations.
      An important intermediate step towards that ideal is the collection of data on
      pain and other symptoms, but also validated quality of life parameters on well
      defined groups. Only by widening the scope of analgesic studies to include these
      dimensions can we hope to define appropriate strategies for more rational
      healthcare.

PMID- 8534527
TI  - Towards a high standard of surgical oncology throughout Europe.
AB  - To retain their role in co-ordinating the multidisciplinary management of cancer,
      surgeons must adapt to new developments in oncology. In addition to technical
      skill in operative surgery, all surgeons treating cancer patients must add new
      information in tumour biology, chemotherapy and radiotherapy to their range of
      knowledge. Such a broad approach is needed nowadays in order to give a valid
      clinical opinion and is indispensable in the planning of operative strategies.
      Although considerable differences in cancer treatment exist within Europe,
      centres of excellence can be defined. The European Society of Surgical Oncology
      is planning, with the co-operation of national surgical oncology groups, to
      devise Guidelines for Good Practice in Surgical Oncology which will be acceptable
      throughout Europe. Identification of centres for training, registration and
      accreditation of trainees and a system of continuing education for established
      surgical oncologists will be proposed. The aims of these proposals are (i) to
      promote excellence in treatment, (ii) to facilitate an exchange of information,
      (iii) to encourage participation in clinical trials, (iv) to improve education of
      medical and para-medical personnel about oncology and (v) to point the way to
      research opportunities. In medical practice abundant evidence exists that (a) a
      high standard of clinical care promotes educational activity, (b) good education
      stimulates research and (c) research in turn activates improvements in service
      and care. Because of its complexity and the need to involve many disciplines in
      its management, the treatment of patients with cancer requires a high standard of
      professional training and competence. Moreover, because of rapid developments in
      cancer research and treatment, mechanisms for continuing medical education for
      oncologists are essential.

PMID- 8534528
TI  - The psychiatrist's perspective on quality of life and quality of care in
      oncology: concepts, symptom management, communication issues.
AB  - The important prevalence of psychosocial problems and psychiatric disturbances
      that have been reported in oncology, underlines the need for comprehensive
      psychosocial support for cancer patients and their families. Psychosocial support
      is designed to preserve, restore or enhance quality of life. Quality of life
      refers not only to psychosocial distress and adjustment-related problems but also
      to the management of cancer symptoms and treatment side-effects. Psychosocial
      interventions designed for this purpose should be divided into five categories:
      prevention, early detection, restoration, support and palliation. Firstly,
      preventive interventions are designed to avoid the development of predictable
      morbidity secondary to treatment and/or disease. Secondly, early detection of
      patients' needs or problems refers to the assumption that early interventions'
      could have therapeutic results superior to those of delayed support, both for
      quality of life and survival. Thirdly, restorative interventions refer to actions
      used when a cure is likely, the aim being the control or elimination of residual
      cancer disability. Fourthly, supportive rehabilitation is planned to lessen
      disability related to chronic disease, characterised by cancer illness remission
      and progression, and to active treatment. Fifthly, palliation is required when
      curative treatments are likely to no longer be effective, and when maintaining or
      improving comfort becomes the main goal. Psychological interventions are often
      multidisciplinary, with a variety of content. The type of psychological
      intervention ranges from information and education to more sophisticated support
      programmes including directive (behavioural or cognitive) therapies, or non
      directive (dynamic or supportive) therapies. Social interventions usually include
      financial, household, equipment, and transport assistance depending on individual
      and family needs and resources. These interventions may be combined with the
      prescription of pharmacological (psychotropic, analgesic), physical, speech or
      occupational therapies, especially in rehabilitation programmes. Health care
      services devoted to delivery of these interventions are hospital, hospice or home
      based and organised very differently depending on already available community
      resources and local practice.

PMID- 8534529
TI  - Clinical trials and quality of life assessment: the nurses' viewpoint.
AB  - The rationale for quality of life assessment has been largely developed in the
      literature. Quality of life is an important concept in the oncology environment
      because the physical, psychological and social wellbeing of patients are affected
      both by the disease and the related treatments. The relevance of quality of life
      assessment to nursing clinical practice has been discussed by several authors.
      There is a need to use more valid and reliable instruments to plan appropriate
      nursing care, to evaluate and document the effect of nursing interventions. In
      clinical trials, quality of life assessment is being used increasingly to predict
      patients' outcomes and to evaluate medical and nursing interventions. Nurses'
      viewpoints of potential benefits and pitfalls related to quality of life
      assessment are discussed. Among the benefits, it is usually considered that
      therapeutic interventions might be improved. These could be adjusted and
      individualised and the need for supportive care interventions might be evaluated
      more accurately. As for the pitfalls, the quality of life evaluation causes an
      extra burden if its implementation is not properly co-ordinated and if poor or
      incomplete guidelines are provided to patients and staff. Proposals for
      implementing effective quality of life assessment in clinical trials are
      discussed. Basic requirements, such as preliminary instructions, guidelines for
      administration of the questionnaire and proposals for reducing missing
      evaluations, are presented.

PMID- 8534530
TI  - [A new method of studying gastric emptying in gastrectomized patients].
AB  - OBJECTIVE: We present a new method of assessment of gastric emptying in
      gastrectomized patients. PATIENTS AND METHODS: The gastric emptying of non
      digestible solids were studied in two groups of gastrectomized patients, the
      Billroth II (n = 25) and the Roux-en-Y (n = 36) to relate the gastric emptying
      with the postgastrectomy symptoms. RESULTS: The food retained in the gastric
      stump is related with significance with the presence (p = 0.01) and the absence
      (p = 0.02) of markers. The patients operated on with the Billroth II technique
      present a higher frequency of markers in the gastric stump (40% over 19.4% with
      the Roux-en-Y). The markers in the gastric stump are more common with the
      symptoms of pyrosis, nausea, bilious vomit, diarrhea and the postoperative
      gastritis of alkaline reflux. CONCLUSIONS: The method of gastric emptying of non
      digestible solids is a valid and reliable study of the gastric emptying and
      should be carried out in all candidates for endoscopy because it is harmless and
      easy to perform and evaluate.

PMID- 8534531
TI  - [Efficacy of 6-mercaptopurine in the treatment of inflammatory bowel disease].
AB  - OBJECTIVE: To assess the efficacy of 6-mercaptopurine in I.B.D. treatment.
      PATIENTS: 21 patients with chronic active disease (8 patients with ulcerative
      colitis and 13 with Crohn's disease) and mean follow-up 5 years for both diseases
      (range ulcerative colitis 1-11 and Crohn's disease 1-14 years, respectively). The
      indications of inmunosuppressor treatment were: corticosteroid dependence (3
      ulcerative colitis; 6 Crohn's disease), refractory disease (5 ulcerative colitis;
      4 Crohn's disease), fistulae (5 Crohn's disease) and perianal disease (4 Crohn's
      disease). All patients received a mean dose of 30 mg/day of prednisone. Complete,
      partial and clinical remission, of failure of treatment are defined. RESULTS: The
      mean dose of 6-mercaptopurine was 90 mg/day with a response mean time of 3.4
      months and 12 months of duration (range 1-36). Complete or partial clinical
      remission was achieved in 77.7% of all the patients (steroid dependent 88.8%,
      refractory disease 77.7%, fistulae 40%, perianal disease 100% of all the patients
      (steroid dependent 88.8%, refractory disease 77.7%, fistulae 40%, perianal
      disease 100%), in 87% of ulcerative colitis patients (steroid dependent 100%,
      refractory 80%) and in 61.5% of Crohn's disease patients (steroid dependent
      83.7%, refractory disease 75%). Secondary effects were observed in two patients.
      CONCLUSIONS: Our results suggest that 6-mercaptopurine is an effective and safe
      drug in the treatment of patients with ulcerative colitis and Crohn's disease in
      corticosteroid dependent, refractory and perianal disease, its efficacy being
      less in fistulae.

PMID- 8534532
TI  - [Incidence of malignancy in millimetric polyps].
AB  - This paper is based on the analysis of 178 polyps of 5 mm or less (polyps we have
      termed "millimetric") studied in the Endoscopy Department of "La Paz" Hospital,
      Madrid, during 1993. All polyps fulfilling these characteristics detected during
      this period are included. The 178 polyps represent 43.4% of all polyps (N = 410)
      found on colonoscopy in this department in this period. The variables considered
      in the study protocol include age, sex, localization, morphology and histological
      examination, with particular attention to high risk histological lesions such as
      signs of possible malignancy.; we also performed a comparative study between the
      results obtained from the 178 millimetric polyps (Group I) and the 232 polyps
      greater than 5 mm (Group II) obtained during the same period. The endoscopic
      technique for the resection of the polyps was evaluated together with its
      possible complications. Although there were no significant differences found in
      respect to age, sex and location, there were morphological differences with a
      greater number of pediculated or semi-pediculated polyps in Group I whilst there
      were more sessile polyps in Group II. Adenomatous polyps were the most frequent
      (84%) in both groups. There was a greater incidence of signs of possible early
      malignant changes in Group II polyps (10) than in Group I (3.3%). The conclusions
      which may be drawn from our study are that it is clinically advisable to excise
      all polyps of 5 mm or less as the frequency of high risk histological changes is
      not negligible (3.3%), and excision is not problematic as the technique is easy
      and there have been no complications in our series.

PMID- 8534533
TI  - [Comparative study of the efficacy and tolerance of 2 types of colon cleansing].
AB  - OBJECTIVE: To examine if (hypothesis): orally administered colon cleansing with 3
      liters of balanced electrolyte/polyethylene glycol solution is superior to the
      standard method of bowel preparation with senna laxatives and sodium phosphate
      enemas. STUDY FACTORS: 1st) Quality of colon cleansing estimated by the attending
      endoscopist. 2nd) Patient tolerance. METHODS:  DESIGN: prospective randomized
      trial, blind to the endoscopist, comparing two methods of bowel preparation:
      group A received 3 L of the balanced electrolyte/polyethylene glycol solution the
      night before the procedure and group B was instructed to ingest 75 ml of a senna
      laxative the day before the colonoscopy and sodium phosphate enemas per rectum
      b.i.d. starting 2 days before the examination and again the morning of the
      procedure. Assessing criteria: 1st) Questionnaire filled by the attending
      endoscopist immediately after the completion of the colonoscopy. 2nd)
      Questionnaire filled by the patient the day after the procedure. PATIENTS: 
      INCLUSION CRITERIA: all the patients addressed to our Unit for colonoscopy (18
      patients refused to participate). EXCLUSION CRITERIA: severe cardiovascular
      disease, decompensated diabetes mellitus and severe disease or neurological
      derangement that prevented collaboration (35 patients). Two hundred and sixteen
      patients were initially included, 110 in group A and 106 in group B; in 39
      patients (18 in group A and 21 in group B) colonoscopy could not be completed for
      causes others than bowel preparation and were excluded for further evaluation by
      the endoscopist, thus, quality of bowel preparation was evaluated in 92 patients
      in group A and in 85 patients in group B; 83 patients (43 in group A and 40 in
      group B) did not answer the questionnaire, or did it incorrectly, thus, tolerance
      was evaluated in 67 patients in group A and in 66 patients in group B. RESULTS:
      In 2 patients in group A (2.2%) and in 9 patients in group B (10.6%) colonoscopy
      could not be completed because of solid stool (p = 0.045). Mucosal visualization
      was better in group A than in group B (p = 0.0108). A total of 11.9% of the
      patients in group A and 25.8% of the patients in group B found the preparation
      hard or very hard to tolerate (p = 0.0001), patients in this latter group
      presented more frequently abdominal cramps (p = 0.0004), and distress (p <
      0.00001), and dizziness (p = 0.0031). Bad tolerance in group B was primarily due
      to the rectal enemas (p < 0.0001). CONCLUSIONS: Bowel preparation for colonoscopy
      with 3 L of orally administer balanced electrolyte/polyethylene glycol solution
      (PEG) results in a better colon cleansing and is better tolerated than the
      classical preparation consisting in oral purge and rectal enemas.

PMID- 8534534
TI  - [Perforation of hollow viscera in abdominal injuries].
AB  - OBJECTIVE: This is a retrospective study to evaluate our results in the treatment
      of abdominal trauma. DESIGN: We have analysed the incidence, the clinical
      characteristics, the diagnosis, the indications for laparotomy, the therapeutic
      methods and the morbidity-mortality. During the last 14 years we have operated on
      29 hollow viscus injuries. They were divided into two groups: Eleven with
      penetrating or open trauma and 18 with blunt or closed traumatism. RESULTS: In
      the cases of blunt trauma 36.8% of injuries were located in the proximal jejunum,
      21% in the terminal ileum, 15% in the colon. In the cases of penetrating trauma,
      small intestinal perforation predominated (46.9%). In 23.5% of the cases the
      colon was affected. Morbidity in blunt trauma was 38.8% and 0% in penetrating
      trauma. The mortality in the two groups has been zero. CONCLUSIONS: The most
      common surgical procedure practised for injuries to the small intestine was
      simple suture, and for injuries to the colon, colostomy. The most usual surgical
      procedures in penetrating trauma were simple suture in all small intestine
      injuries and for colonic lesions half had primary closure and half suture plus
      colostomy.

PMID- 8534535
TI  - [Usefulness of ultrasonography in the early diagnosis of hepatocarcinoma in
      patients with liver cirrhosis].
AB  - OBJECTIVE: To assess the efficacy of a screening program of ultrasonography
      (U.S.) every six months in the early diagnosis of HCC in liver cirrhosis
      patients. PATIENTS AND METHODS: We review retrospectively the 99 HCC detected by
      U.S. in our service from January 1991 to July 1994. We compared patients in the
      ultrasonography screening program (Group I) with patients who did not (Group II)
      and, also with, patients with a previous diagnosis of cirrhosis (Group IIa) and
      patients with simultaneous HCC diagnosis of and cirrhosis (Group IIb). Liver
      function, the tumor size and extension, and the chance of treatment at the time
      of diagnosis were analyzed in each group. RESULTS: Twenty (58%) HCC out of 34
      from group I single nodules < 5 cm in diameter vs seven (11%) out of 65 from
      group II (p < 0.001) were detected and this difference persisted between group I
      and groups IIa and IIb (p = 0.002 and p < 0.001). Most patients with grade C
      Child-Pugh's score (24 from 27) in each group showed a > 5 cm or multinodular
      HCC. Ten patients from group I were treated vs 4 from group II (p = 0.001).
      CONCLUSIONS: Ultrasonography screening program is useful in the early diagnosis
      of HCC in liver cirrhosis patients and increases the chances of treatment.

PMID- 8534536
TI  - [Advances in the topical steroid treatment of inflammatory bowel diseases].

PMID- 8534537
TI  - [Elastic band ligation: preliminary experience in esophagogastric varices].
AB  - Endoscopic ligation is a new technique that shows an efficacy for acute
      hemorrhage and prevention similar to sclerotherapy. Its principal advantage is
      the smaller number of complications (2%), which seem to be related to the
      presence of post-treatment ulcers which are indeed more extensive but more
      superficial. In our preliminary study on 8 patients, eradication of varices in
      62.5% was obtained. The mean number of bands placed at each ligation session was
      of 2.4 +/- 0.96 and the mean number of treatment sessions to achieve the
      eradication was 3.4 +/- 1.5. The complications that appear during the positioning
      of bands, a minimum bleeding was observed during the polyp formation, and in one
      occasion, the partial detachment of an eschar followed the bleeding was also
      observed. Rebleeding occurred in two patients (25%), and in other patient,
      spontaneous bacterial peritonitis was observed. The two patients who presented
      recurrent variceal bleeding, received a transjugular intrahepatic portosystemic
      shunt to control their hemorrhage.

PMID- 8534538
TI  - [Duodenal gangliocytic paraganglioma].
AB  - We report a case of duodenal Gangliocytic Paranglioma in a 73 year old man, who
      presented with a history of melena. An upper gastrointestinal barium study showed
      a polyp located in the second portion of the duodenum. This lesion was
      endoscopically resected. Pathological examination revealed a Gangliocytic
      Paraganglioma. We describe the general characteristics of this neoplasm, as well
      as the theories about its histogenesis.

PMID- 8534539
TI  - [Intestinal obstruction and sepsis caused by Torulopsis glabrata].
AB  - A 27-year-old woman previously diagnosed of aplastic anemia secondary to
      treatment with gold salts for rheumatoid arthritis, presented with an episode of
      intestinal occlusion with acute renal failure. A CT scan revealed dilated
      intestinal loops, thickening of the ileum wall without cecal involvement, and
      multiple punctuate lesions (micro-abcesses) of liver, spleen and kidneys. At
      laparotomy, one meter of proximal jejunum was resected. The cultures of jejunal
      biopsy specimens yielded Torulopsis glabrata. The patient underwent multiorgan
      failure and died on the 8th postoperative day.

PMID- 8534540
TI  - [Liver abscess caused by Streptococcus anginosus].
AB  - Pyogenic liver abscess is a relatively rare disease, often concerning elderly
      patients in bad general condition and with underlying diseases. We report the
      case of a 77-year-old female with gastric cancer and liver abscesses by
      Streptococcus anginosus.

PMID- 8534541
TI  - [Chronic liver disease exacerbated during alpha-interferon treatment].
AB  - A 27 year old male patient was referred to our clinical unit because of marked
      elevation of serum bilirubin (up to 15.3 mg/dl), ASAT (563 U/l) and ALAT (845
      U/l) were detected after institution of therapy with alpha interferon. The
      patient had been previously treated because of persistent slight elevation of
      serum transaminases, serological markers of hepatitis B virus and hepatitis C
      virus being both negative. Liver histology was consistent with chronic active
      hepatitis. Antinuclear, anti smooth muscle and antimitochondrial autoantibodies
      were all negative, although anti smooth muscle antibodies became positive (1/40)
      after interferon therapy. The drug was withdrawn, prednisone was instituted, and
      transaminases and bilirubin values returned to normality.

PMID- 8534542
TI  - [Arterial revascularization of liver graft with PTFE vascular prosthesis].
AB  - When the hepatic artery is not available in liver transplantation because of its
      bad quality or low flow, arterial grafts from the donor have to be used to obtain
      arterial blood flow from the aorta. The case of use of a vascular PTFE prosthesis
      when no vascular grafts were available is presented, with good outcome 6 months
      after transplantation.

PMID- 8534543
TI  - [Psoas abscess secondary to colonic neoplasm].

PMID- 8534544
TI  - [Topical injection of steroids in benign esophageal stenosis refractory to
      dilatation treatment].

PMID- 8534545
TI  - [Immunohistochemistry of hormone receptors in pancreatic cancer].

PMID- 8534546
TI  - [Chylous ascites associated with liver cirrhosis treated with medium-chain
      triglycerides].

PMID- 8534547
TI  - [Clinico-epidemiological implications of autochthonous infection caused by
      Entamoeba histolytica].

PMID- 8534548
TI  - [Neurotoxicity of nerve agents].

PMID- 8534549
TI  - [Role of cortical motor areas in voluntary movements].

PMID- 8534550
TI  - [Experimental study on hypertensive crises in epileptic seizures--changes in pial
      artery diameter, intracranial pressure and regional cerebral blood flow].
AB  - It is well known that severe hypertension occurs during epileptic seizures, but
      little information is available concerning these hypertensive crises. We
      therefore investigated them by monitoring regional cerebral blood flow (rCBF),
      intracranial pressure (ICP) and pial artery diameter (PAD) in paralyzed
      mechanically-ventilated cats with penicillin-induced seizures. The animals were
      assigned to two groups. In one (Group H), they were maintained in an untreated
      state. In the other (Group C), spinal cord injury was performed in advance to
      prevent the rise in arterial blood pressure during the seizures. In both groups,
      the values of the various parameters increased during seizure activity, but the
      increases in group H, were greater than in group C. In both groups, PAD, rCBF and
      ICP increased immediately at the onset of the seizures with no hypertension. In
      group H, further increases in PAD, rCBF, and ICP were found concurrent with the
      elevation of arterial blood pressure in the latter half of the seizure, while in
      group C, rCBF decreased concurrent with the increase in ICP in the latter half of
      the seizure, although PAD was found to be maximal. These findings suggest that
      hypertensive crises during epileptic seizures represent a protective mechanism to
      maintain perfusion pressure.

PMID- 8534551
TI  - [Migration, differentiation and integration of an immortalized neural cell line
      transplanted into the neonatal and adult mouse brain].
AB  - An immortalized neural cell line V1 was transplanted stereotaxically into the
      cerebellum and hippocampus of developing and adult mice, and the mode of
      migration, differentiation and arrangement of the grafted cells were examined by
      labeling the grafted cells with DiI (1, 1'-dioctadecyl-3, 3, 3', 3'
      tetramethylindocarbocyanine perchlorate) and immunohistochemical staining. This
      cell line was established by transduction of the temperature-sensitive allele
      tsA58 of SV40 large T antigen oncogene into mouse hypothalamic cells. Grafted
      cells did not show any tumorigenicity for a long time. Some of the cells grafted
      into the neonatal cerebellum and hippocampus were arranged along the host
      cortical layer and showed neuronal or glial differentiation according to the
      grafted site. The cells grafted into adult cerebellum also showed migration and
      arrangement along the host cortical layer as well as morphological
      differentiation into glial cells in a manner similar to that of transplantation
      to the neonate. On the other hand, the cells grafted into the adult hippocampus
      made only clusters without forming an organized arrangement. These findings
      suggest that the grafted cells are integrated into the developmental processes of
      the host brain, and the mode of differentiation and arrangement of the grafted
      cells depends on the microenvironment of the different developmental stages of
      the host brain. The involvement of host blood vessels and astroglial framework in
      the migration and arrangement of the grafted cells was also suggested.
      Furthermore, these findings suggest the plasticity of the host brain in response
      to the grafted cells and the possibility of reconstructing the host brain with
      this multipotential neural cell line.

PMID- 8534552
TI  - [Hypothalamic-adenohypophysial function of corticotropin releasing hormone (CRH)
      ACTH system in brain death].
AB  - To evaluate the hypothalamic-adenohypophysial function of corticotropin releasing
      hormone (CRH)-ACTH system in brain death, basal serum values of ACTH and cortisol
      was measured, and in addition, insulin-tolerance test (ITT) and CRH stimulation
      test was performed is 28 brain death cases. Basal levels of ACTH were low-normal,
      whereas those of cortisol were high-normal, and no correlation was observed
      between them. There was no correlation between these levels and the age, sex,
      cause of the brain death, and the incidence of hypotention. However, basal ACTH
      value significantly decreased within a few days (p < 0.01), and ACTH was
      undetectable in all cases 5 days after the diagnosis of the brain death. On the
      other hand, ITT and CRH test was negative in all cases. These results suggest
      that some degree of adenohypophysial function of ACTH secretion remains for a few
      days after the diagnosis of the brain death. Compared with other adenohypophysial
      hormones of the brain death cases in previous reports, however, ACTH was lower,
      decreased more rapidly, and did not response to the direct pituitary stimulation
      test, the CRH test. These results further suggest that disturbance of ACTH
      secretion occurs from an early stage in the brain death cases.

PMID- 8534553
TI  - [MRI of the pituitary adenomas with reference to the hormonal activity].
AB  - Many studies in Magnetic Resonance Imaging (MRI) of pituitary adenomas are
      already performed. However, few reports exist about MRI findings of pituitary
      adenomas with reference to the hormonal activity, therefore, we evaluated this
      problem on the viewpoint of the signal intensity in MRI and pathological
      features. Fifteen patients with growth hormone producing adenoma (GH-group), 6
      patients with prolactin producing adenoma (PRL-group), 15 patients with
      endocrinologically non-functioning adenoma (Null-group) and 9 cases with normal
      pituitary gland (normal control group) were examined. Signal intensity values in
      adenoma (or anterior lobe in normal control group) and in pons as standard value
      were measured in each cases, then their rates were calculated as signal intensity
      ratio (SIR). In 24 cases (14 in GH-group, 3 in PRL-group, 7 in Null-group),
      cellular density were examined with surgically resected specimens. In the T1
      weighted images (T1 WIs), PRL-group and Null-group presented more hypointense
      tendency than normal control group. In the T2-weighted images (T2 WIs), only Null
      group presented more hyperintense tendency than other groups. But significant
      correlation was not observed between SIR and cellular density.

PMID- 8534554
TI  - [Cooperative multicentric study on posttraumatic epilepsy].
AB  - A multicenter cooperative study was conducted to investigate factors influencing
      posttraumatic epilepsy (PTE) and to evaluate the prophylactic effect of
      anticonvulsants. A retrospective study of 102 PTE patients revealed the following
      typical clinical features: occurrence in young males, traffic accidents,
      contusion and/or cerebral hematoma. The latent period after the injury was longer
      in children. The percentage of EEG paroxysmal activity gradually increased as the
      generalized abnormality diminished. A retrospective-prospective study of 1998
      patients who suffered a head injury between 1984 and 1988 was conducted till
      1994. During the follow-up period, 62 patients (3.1%) developed PTE. The drop-out
      cases were excluded, and the 154 cases followed at least two years were analyzed.
      Statistical analysis of differences between patients with and without PTE
      suggested following factors: young, immediate early epilepsy (within 24 hours
      after injury; IMEE) and early epilepsy (within one week after injury). The risk
      with the highest relative risk rate was early epilepsy. Multiple regression
      analysis revealed that three factors, IMEE, early epilepsy and young age,
      contributed to the prediction of PTE. There was no significant difference in the
      percentage of patients having PTE in the group treated with anticonvulsants and
      the untreated group. Anticonvulsant treatment after head injury was unlikely to
      have a prophylactic effect on the development of PTE.

PMID- 8534555
TI  - [Effect of diabetic control on the progression of neuropathy].
AB  - We investigated the relationship between blood levels of HbA1, an indicator of
      diabetic control, and the polyneuropathy index (PNI), an indicator of diabetic
      polyneuropathy. A total of 175 patients with non-insulin-dependent diabetes
      mellitus were followed for more than 3 years and were subjected to a series of
      motor conduction studies every 1 to 3 years. The PNI was calculated as a mean
      percentage of normal values for 12 indices derived from the conduction velocity
      and long-distance latency in motor conduction studies of 4 nerves. The mean
      follow-up period was 5.0 years, and during that time the mean decrease in the PNI
      was 2.7%. There was a significant negative correlation between mean HbA1 levels
      (X) and the percent changes in PNI per year (Y), and the equation for the
      regression line was Y = -0.102X + 0.37 (r = 0.283, p < 0.001). The higher the
      HbA1 level during this period, the larger the decline in PNI was. In patients
      with low initial PNI levels the change in PNI tended to be small in spite of high
      HbA1 levels. Likewise, in patients with high initial PNI levels the decrease in
      PNI tended to be large despite relatively good control of their HbA1 levels.
      However, since there were many patients whose HbA1 levels were not correlated
      with the reduction in PNI, there may be some unknown factors, possibly genetic,
      that play a role in the progression of polyneuropathy in diabetic patients.

PMID- 8534556
TI  - [Familial posterior cortical atrophy with visual agnosia and Balint's syndrome].
AB  - We report a patient of posterior cortical atrophy with progressive visual
      agnosia, Balint's syndrome and dementia in which posterior cortical atrophy with
      similar characteristics on CT and progressive dementia were found in a sister.
      The patient was a 75-year-old woman who noted the onset of a progressive visual
      disorder at the age of 70, and whose family first noticed disoriented behavior at
      around the same period. Ophthalmologic examinations revealed mild cataract but no
      evidence of peripheral optic nerve or retinal lesions. Neuropsychological
      examination showed right homonymous hemianopia, visual agnosia, Balint's
      syndrome, mild transcortical sensory aphasia, Gerstmann's syndrome,
      constructional apraxia, mild ideomotor apraxia and memory disorder. MRI showed
      marked dilatation of both lateral ventricles, especially the posterior horns, and
      severe atrophy of the occipital lobes, hippocampus, and the parahippocampal
      gyrus. Assessment of regional cerebral blood flow by IMP-SPECT revealed a
      generalized decrease in the temporo-parieto-occipital region bilaterally. The
      patient's sister began to show evidence of progressive dementia at 80 years of
      age and CT of the brain revealed marked atrophy, predominantly in the occipital
      lobes, similar to that of the patient. We believe this to be the first report of
      posterior cortical atrophy with a positive family history, suggesting the
      possibility of a hereditary syndrome.

PMID- 8534557
TI  - [Penetrating head injury caused by weed--case report].
AB  - A case of penetrating head injury caused by weed was reported. A 69-year-old man
      fell from a bicycle and was stuck by the hard stalk of weed through the right
      nasal cavity. On admission the patient was fully alert and with no neurological
      deficits. The weed was pulled out at an out-patient department and then he became
      semicomatose and hemiplegic on the left side together with an occurrence of nasal
      bleeding. Subsequent computed tomographic (CT) scan showed an intracerebral
      hematoma in the right frontal lobe. The hematoma was immediately evacuated and
      the dural defect, lateral to the cribriform plate, was closed. It is stressed
      that neuroradiological evaluation with CT scan and/or magnetic resonance imaging
      (MRI) is mandatory because an information about an anatomical location of
      penetrating objects and intracranial complications are essential to a decision
      making of surgical strategy. The objects should be urgently removed in a surgical
      exposure of the intracranial lesion and the contused brain should be debrided
      with a repair of the lacerated dura mater.

PMID- 8534558
TI  - [Anosognosia, 2)anosodiaphoria].

PMID- 8534559
TI  - [A 75-year-old man with parkinsonism and sudden death].
AB  - We report a 75-year-old man with parkinsonism who died suddenly. The patient was
      well until 64 years of the age when he had an onset of tremor in his left hand.
      He was treated with a medicine in another hospital, and his tremor subsided. Five
      years after the onset, he started to note difficulty in fine finger movements and
      gait disturbance. He tended to lean backward with frequent falls. He was treated
      with bromocriptine, trihexyphenydil, and L-dops without apparent improvement. He
      visited our out patient clinic on November 11, 1993 when he was 75 years of the
      age. Neurologic examination at that time revealed an alert and well oriented man
      in no acute distress. Higher cerebral functions were intact. In the cranial
      nerves, he showed restriction in the upward as well as down ward gaze (40% of
      normal). He showed masking of the face and spoke in small voice. He walked in a
      stooped posture with small steps; retropulsion was present. Muscle rigidity was
      moderately positive in the neck, however, no rigidity was noted in the limbs. No
      abnormal involuntary movements were seen. He showed moderate bradykinesia and
      difficulty in finger tapping. Muscle stretch reflexes were normally elicited and
      the plantar response was flexor bilaterally. Sensation was intact. The autonomic
      nervous system appeared intact. He was treated with 300 mg/day of Sinemet with
      marginal improvement in his balance. In February 4, 1994, he had a common cold.
      On the next day, his parkinsonism worsened and he became unable to walk by
      himself. He was found unconscious in the bathroom on the same day. He was brought
      to our hospital by an ambulance. Upon arrival, he was unresponsive and was not
      breathing. Blood pressure could not be measured. Pupils were dilated without
      reaction to light. Cardiac resuscitation was attempted, however, ventricular
      fibrillation appeared on an EEG monitor, and he was pronounced dead at eleven
      o'clock in the morning. The patient was discussed in a neurological CPC, and the
      chief discussant arrived at the conclusion that the patient had progressive
      supranuclear palsy because of vertical gaze palsy, axial rigidity, and poor
      response to levodopa. Regarding the cause of his sudden death, the chief
      discussant thought that he developed pulmonary embolism. Postmortem examination
      revealed non-bacterial thrombotic endocarditis in the heart, but this did not
      appeared to be related to his sudden death. Multiple disseminated small emboli
      were found occluding small arteries of the left lung; this was consistent with
      acute pulmonary embolism, and this was thought to be the cause of his sudden
      death. In the central nervous system, marked atrophy of the globus pallidus was
      noted; both internal as well as external segments showed marked atrophy; no
      myelinated fibers were seen in the globus pallidus. Neuronal cell loss was marked
      in the globus pallidus, the subthalamic nucleus, and the substantia nigra. No
      Lewy bodies or tangles were seen. The histologic diagnosis was consistent with
      pallido-nigro-luysian atrophy. Brownish pigments such as seen in Hallervorden
      Spatz disease were seen in the globus pallidus. In addition, formy spheroids were
      seen in the substantia nigra. However, iron deposits were not so strong as to
      suggest Hallervorden-Spatz disease. Pallido-nigro-luysian atrophy is a rare
      neurodegenerative disorder. It is interesting to note that this condition may
      mimic progressive supranuclear palsy or pure akinesia clinically.

PMID- 8534560
TI  - Tobacco and smoking cessation in dentistry.

PMID- 8534561
TI  - Sugar-free medicines.

PMID- 8534562
TI  - Location of bone and tooth fragment following mandibular fracture.

PMID- 8534563
TI  - The provision of orthodontic treatment.

PMID- 8534564
TI  - The future of NHS dentistry.

PMID- 8534565
TI  - The future of NHS dentistry.

PMID- 8534566
TI  - The future of NHS dentistry.

PMID- 8534567
TI  - Alternative access to Medline via Compuserve.

PMID- 8534568
TI  - Sugar dust caries.

PMID- 8534569
TI  - Smoking cessation counselling--a role for the dental profession?
AB  - Whilst several studies have investigated the views of North American dentists on
      providing advice to patients on stopping smoking, the role of their UK
      counterparts in this area is uncertain. Thus this study aimed: 1. to examine
      dentists' awareness of the effect of smoking on general and oral health, 2. to
      determine their views on counselling patients to give up smoking, 3. to
      investigate the extent to which they currently engage in this activity, and 4. to
      survey barriers to providing such advice. Data were collected via a postal
      questionnaire mailed to 587 Scottish dental practitioners, of which 448 (76.3%)
      were completed and returned. The importance of smoking as a cause of ill health
      and death was acknowledged universally, and most were aware of the adverse
      consequences of smoking on the oral tissues. Over half the respondents (245 or
      54.7%) thought dentists had a role in counselling patients to give up smoking and
      whilst 107 (23.8%) were uncertain, the remaining 95 (21.2%) felt this was outside
      their remit. Nonetheless, 384 (85.6%) reported that, at least occasionally, they
      advised patients to quit. Lack of time was seen as an important barrier to
      tobacco counselling, as was lack of training. Further studies are required to
      determine the most useful strategies or approaches, and to determine their
      effectiveness.

PMID- 8534570
TI  - Localising maxillary canines using dental panoramic tomography.
AB  - Impacted maxillary canine teeth occur in about 2% of the population. Late
      detection of palatal canines may have treatment implications for the patient and
      medicolegal implications for the dental practitioner. Dental panoramic tomograms
      (DPT) are widely taken in practice. Image formation in dental panoramic
      tomography results in relative magnification of objects placed palatal to the
      image layer and relative diminution of objects buccal to it. This provides a
      possible means of bucco-palatal localisation of teeth. The aim of this study was
      assess the validity of DPTs in locating ectopic canines using the vertex occlusal
      view (VO) as the gold standard. One hundred pairs of radiographs showing 139
      ectopic canines were examined. Using the DPT, it was possible to accurately
      predict the position of a palatally displaced crown in about 80% of cases. The
      DPT alone is not sufficient for canine localisation, but clinical evidence and
      suggestion of ectopic positioning on a DPT should warrant further radiographic
      investigation. Careful interpretation of a radiograph widely used in practice may
      lead to earlier detection of palatal canines.

PMID- 8534571
TI  - The oral health of minority ethnic communities in the United Kingdom.
AB  - The oral health status of minority ethnic groups is a critical issue for
      practitioners in today's multicultural society. The National Dental Health
      survey, conducted by the OPCS, provides baseline information on the oral health
      and oral health related behaviour of the population in the United Kingdom but not
      specifically relating to the minority ethnic communities. To date, little is
      known concerning oral health status and self-reported oral health related
      behaviours among minority ethnic communities in this country. Following a review
      of the published literature, this paper will address two questions: how has
      ethnicity been used as a variable by dental researchers and, what is known of the
      oral health status of minority ethnic groups? Other background variables are
      considered which might explain the differences in oral health status between
      these communities and the indigenous population, and recommendations are made
      concerning further research in this area.

PMID- 8534572
TI  - Ankylosis: an orthodontic problem with a restorative solution.
AB  - This case illustrates a restorative approach using adhesive techniques to
      overcome the aesthetic and functional problems associated with infraclusion of a
      mandibular canine tooth resulting from ankylosis. In this case a diagnosis of
      ankylosis was confirmed after 3 months of fixed appliance orthodontic therapy
      failed to extrude the tooth.

PMID- 8534573
TI  - Centenary year of scientific papers in the British Dental Journal.

PMID- 8534574
TI  - Ganglioside extraction from erythrocytes: a comparison study.
AB  - Several methods for ganglioside extraction from erythrocytes have been compared.
      Our results show that ganglioside extraction is unfavourably affected by the
      addition of the solvents as a mixture and by the use of less polar solvents and
      by a lower total solvent-to-sample ratio. In accordance with our previous
      observation on cholesterol and phospholipids, the distribution of gangliosides
      could be uneven in an apparently monophasic extraction solvent mixture. The
      uneven distribution occurred during and also after the extraction (in filtration
      and centrifugation). In the recommended method using 19 volumes of
      methanol/chloroform (2:1) solvent in a one-step extraction, the above
      disadvantages in ganglioside extraction and quantification are kept under
      control. This method appears simple and it gives a high recovery of gangliosides.

PMID- 8534575
TI  - Soft tissue architecture and intramuscular pressure in the shoulder region.
AB  - Soft tissue architecture including muscle insertions were studied in the shoulder
      region by dissecting three male cadavers. These dissections demonstrated that m.
      supraspinatus and mm. infraspinatus/teres minor were located in two separate,
      closed compartments limited by bony walls and tense stiff fascia. M.
      supraspinatus was composed of two parts which differed with respect to attachment
      site, fibre orientation, and muscle structure although they were similar with
      respect to muscle fibre length. Muscle structure, fascia and insertion sites
      should be taken into account in biomechanical modeling of the shoulder.
      Intramuscular pressures in the shoulder muscles were recorded in healthy females
      during voluntary isometric contractions performed in various arm positions, and
      at different contraction levels and measuring depths. Intramuscular pressure in
      m. supraspinatus during 30 degrees shoulder abduction: 58 (33-70) mmHg, exceeded
      the intramuscular pressure during 30 degrees flexion: 29 (7-40) mmHg. In m.
      infraspinatus lower values were registered. A simple relation between
      intramuscular pressure and measuring depth did not exist in the soft tissue above
      fossa supraspinata. During contractions a steep increase in intramuscular
      pressure was seen at a depth corresponding to the transition from m. trapezius to
      m. supraspinatus. The intramuscular pressure measurements showed wide regional
      heterogeneity at the same measuring depth during contractions, which is likely to
      be due to the complex anatomy found in this region. The results show the
      significance of the anatomy for the increase in intramuscular pressure during
      contractions. This in turn may impair muscle blood flow and thus affect muscle
      function over prolonged periods of time.

PMID- 8534576
TI  - Gastrulation inducing potencies of endophyll and Rauber's sickle in isolated
      caudocranially oriented prestreak avian blastoderm quadrants (or fragments) in
      vitro.
AB  - Unincubated quail and prestreak chicken blastoderms were sectioned into cranial,
      caudal and lateral quadrants and cultured in vitro. Whilst in the caudal and
      lateral quadrants (containing both endophyll and Rauber's sickle material) a
      primitive streak (PS) developed, in the cranial quadrants (where merely central
      endophyll is present) only an ectoblastic thickening (early gastrula: phase I of
      gastrulation) appeared. If, however, sickle material was grafted on a cranial
      quadrant then a PS developed (phase II of gastrulation). In the anti-sickle
      region (lacking sickle material and endophyll) no gastrular differentiation
      occurred spontaneously. The grafting of endophyll and/or Rauber's sickle evokes
      here also phase I or II of gastrulation. When the endophyll was removed from the
      caudal quadrant no PS appeared. If, however, endophyll was replaced, a PS and
      neurula developed. Our study demonstrates that the presence of endophyll is
      necessary to obtain an early gastrular development (phase I of gastrulation). It
      seems also to have an influence on the formation of the future neurectodermal
      region by induction of a thickening of the cranial upper layer. Only when both
      endophyll and sickle material were present, a PS formed in caudal quadrants. In
      the caudal quadrant, the endophyll (which seems to represent the vegetative pole
      of the avian blastula) does not regenerate, neither from the upper layer, nor
      from Rauber's sickle (containing blastoporal material: Callebaut and Van Nueten:
      1994).

PMID- 8534577
TI  - Myoepithelial cells and innervation in the infraorbital gland of the Japanese
      serow (Capricornis crispus).
AB  - Both the apocrine and the sebaceous portions of the infraorbital gland of the
      Japanese serow were examined to obtain morphological evidence related to the
      mechanism of secretion. The examination was carried out by an immunohistochemical
      method using antibodies against alpha-smooth muscle actin for myoepithelial cells
      and protein gene product 9.5 for nerve fibers. Immunostaining for alpha-smooth
      muscle actin was apparent in the myoepithelial cells of apocrine tubules and
      varied within the same glands and among individual glands. Immunostaining for
      protein gene product 9.5 revealed the presence of nerve fibers around apocrine
      tubules. The immunoreactive nerve fibers were fine or varicose. In the sebaceous
      glands of the ordinary type and of the modified type, no immunoreactivity
      specific for alpha-smooth muscle actin or protein gene product 9.5 was observed.
      These results suggest that apocrine tubular activity of the infraorbital gland
      occurs independently in each tubule and that secretion by the apocrine tubules is
      controlled by the myoepithelial cells via nerve fibers.

PMID- 8534578
TI  - Ultracytochemical localization of ouabain-sensitive K(+)-dependent
      paranitrophenylphosphatase in rat sciatic nerve fibers.
AB  - In order to reveal and characterize Na+,K(+)-ATPase distribution in axon-myelin
      Schwann cell units of sciatic nerves of adult and 15 days old Wistar rats, the
      ultracytochemical lead-paranitrophenyl-phosphatase technique was used. The
      activity of K(+)-dependent paranitrophenylphosphatase, a component of Na+,K(+)
      ATPase, was found on the cytoplasmic side of the axolemma and Schwann cell plasma
      membrane, as well as on the major dense lines of the myelin sheath. K(+)
      paranitrophenylphosphatase activity was localized also at the axoplasmic profiles
      and at the Golgi apparatus of the Schwann cells. Ouabain inhibition made it
      possible to distinguish alpha 1 from alpha 2 and alpha 3 isoforms of Na+,K(+)
      ATPase. The results suggest that the activity of the axolemma and myelin sheath
      is determined by alpha 2 and alpha 3 isozymes. The enzyme activity of the Schwann
      cell plasma membrane and Golgi complex was not visibly influenced by ouabain.
      These results suggest that the activity of these glial structures is determined
      mainly by alpha 1 isozyme.

PMID- 8534579
TI  - The basal plasma membrane and lamina densa of uterine epithelial cells are both
      altered during early pregnancy and by ovarian hormones in the rat.
AB  - Changes in the basal plasma membrane and lamina densa of uterine epithelial cells
      have been studied in the rat during early pregnancy and under the influence of
      progesterone and oestrogen. Both the basal plasma membrane and lamina densa
      become increasingly tortuous by day 6 of pregnancy and this condition is found to
      be predominantly influenced by progesterone. Oestrogen, either alone or in
      combination with progesterone, has a much lesser effect. The lamina densa
      increases in thickness by day 6 of pregnancy and again progesterone is found to
      have the major influence. These alterations are discussed in the context of
      implantation of the blastocyst and we highlight the differing effect that ovarian
      hormones have on different regions of the plasma membrane of uterine epithelial
      cells.

PMID- 8534580
TI  - A combined electron microscopic investigation of the peritoneal mesothelium in
      the rat.
AB  - Visceral and parietal peritoneum of adult Wistar rats was studied by means of
      transmission and scanning electron microscopy. The structure of the peritoneum
      follows a general plan: mesothelium, basal lamina, and submesothelial connective
      tissue layer. Two basic types of mesothelial cells are described: flat and high
      (cubic), as well as transitional forms. A regularity of distribution of these
      cells in the visceral and parietal peritoneal sheets, and in the cover of
      individual organs and regions is described. A functional characterization of the
      different types of mesothelial cells is attempted, based on the differences of
      their cytoplasmic organization. The involvement of the mesothelium in the
      homeostasis in the peritoneal cavity is discussed.

PMID- 8534581
TI  - Immunohistochemical characteristics of cutaneous Herbst corpuscles from beak and
      rictus in domestic pigeon.
AB  - Herbst corpuscles are the avian equivalent to the mammalian Pacinian corpuscles.
      In this study we used indirect peroxidase-anti peroxidase (PAP)
      immunohistochemistry to analyze the distribution in the pigeon cutaneous Herbst
      corpuscles, of several markers which are known to specifically label the axon,
      the Schwann-related and perineurial-related cells in Pacinian corpuscles. The
      distribution of the assessed antigens on Herbst corpuscles was as follows: i) the
      central axon displayed positive immunoreactivity for neurofilament proteins and
      neuron specific enolase; ii) the lamellar cells forming the inner-core were
      positive for S-100 protein and vimentin, whereas fibroblast surrounding them were
      vimentin and epithelial membrane antigen positive; iii) the capsule was focally
      immunolabelled for vimentin, and regularly for epithelial membrane antigen. No
      immunoreactivity was found neither for cytokeratins nor for glial fibrillary
      acidic protein. These observations demonstrate that the immunohistochemical
      profile of cutaneous (beak skin and rictus) Herbst corpuscles in pigeon is
      similar to that of the mammalian Pacinian corpuscles.

PMID- 8534582
TI  - Assessment of coronary vasodilator reserve by N-13 ammonia PET using the
      microsphere method and Patlak plot analysis.
AB  - Noninvasive quantification of regional myocardial blood flow (MBF) has been
      successfully achieved with N-13 ammonia. The microsphere method as a simple
      method for quantifying regional myocardial blood flow was reevaluated in
      comparison with Patlak graphical analysis. In addition coronary vasodilator
      reserve (CVR) was estimated by both methods. METHODS: Dynamic N-13 ammonia PET
      studies were performed in 10 healthy volunteers and 10 patients with coronary
      artery disease at baseline and after dipyridamole infusion (0.56 mg/kg). MBF was
      estimated by the microsphere method at various times and by Patlak graphical
      analysis. In order to reduce the noise level in the microsphere method, MBF
      estimates were also performed after data in 10-40 seconds were averaged. RESULTS:
      In the studies on normal subjects MBF (ml/min/g) determined by the microsphere
      method significantly differs from time to time. However, MBF determined by the
      modified microsphere method [with average (Extraction fraction) x MBF values
      obtained between 100 and 120 sec] linearly correlated well with MBF by Patlak
      graphical analysis (r = 0.97, slope = 0.98, intercept = 0.20). In the studies on
      patients with coronary artery disease a good agreement of the MBF estimates was
      also observed (r = 0.97, slope = 0.98, intercept = 0.22). In the studies on the
      normal subjects and patients with coronary artery disease, CVR obtained by the
      modified microsphere method after correcting the overestimated MBF values also
      correlated well with that by Patlak graphical analysis (r = 0.90, slope = 1.14,
      intercept = -0.15, and r = 0.92, slope = 0.82, intercept = 0.25, respectively).
      CONCLUSION: The modified microsphere method is a very simple and reliable
      approach for quantifying MBF with N-13 ammonia PET which is comparable to Patlak
      graphical analysis. It also makes possible CVR assessment as accurate as Patlak
      graphical analysis.

PMID- 8534583
TI  - Positron emission tomography with 4-[18F]fluoro-L-m-tyrosine in MPTP-induced
      hemiparkinsonian monkeys.
AB  - PET imaging studies with 4-[18F]fluoro-L-m-tyrosine (FMT) in normal macaca
      monkeys showed selective accumulations of radioactivity in the striatum with
      time. In monkeys rendered hemiparkinsonian by intracarotid infusion of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the
      lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in
      both normal and hemiparkinsonian monkeys, and clearly showed a reduction in
      aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned
      striatum. These results show that FMT is promising as a PET tracer for the
      evaluation of central dopaminergic systems in parkinsonism.

PMID- 8534584
TI  - Impaired myocardial fatty acid metabolism detected by 123I-BMIPP in patients with
      unstable angina pectoris: comparison with perfusion imaging by 99mTc-sestamibi.
AB  - The present study was undertaken to determine the potential diagnostic value of
      123I-BMIPP scintigraphy for the detection of altered myocardial fatty acid
      metabolism in patients with unstable angina. Both myocardial metabolic imaging
      with 123I-BMIPP and perfusion imaging with 99mTc-sestamibi were performed at rest
      in 28 patients with unstable angina in the pain-free state. The regional uptakes
      of 123I-BMIPP or 99mTc-sestamibi were scored semiquantitatively (0 = normal, 4 =
      no activity) and compared with the coronary arteriographic findings. Decreased
      uptakes of 123I-BMIPP were observed in 18 patients, and 11 patients had abnormal
      99mTc-sestamibi images. Defect scores of 123I-BMIPP were larger than those of
      99mTc-sestamibi (7.8 +/- 2.1 vs. 5.2 +/- 1.9, p < 0.01). The sensitivity for the
      detection of patients with unstable angina was higher in 123I-BMIPP than in 99mTc
      sestamibi (77% vs. 45%, p < 0.01). The site of the decreased 123I-BMIPP uptake
      corresponded to the most stenotic coronary artery lesion in all patients. Fatty
      acid metabolic imaging with 123I-BMIPP was more sensitive for detecting
      myocardial ischemia than perfusion imaging with 99mTc-sestamibi. 123I-BMIPP may
      be a clue to define the culprit lesion in unstable angina and be helpful to
      decide the best treatment and guide coronary angioplasty.

PMID- 8534585
TI  - Initial clinical experiences with dopamine D2 receptor imaging by means of 2'
      iodospiperone and single-photon emission computed tomography.
AB  - Dopamine D2 receptor imaging was performed with 123I labeled 2'-iodospiperone (2'
      ISP) and single-photon emission computed tomography (SPECT) in 9 patients: 4 with
      idiopathic Parkinson's disease, 2 with parkinsonism, 1 with Wilson's disease and
      2 with pituitary tumor, and the results were compared with the data for 9 normal
      subjects. Following an intravenous injection of 123I-2'-ISP, early (within 30
      min) and late (between 2 and 4 hr) SPECT images were obtained by means of a multi
      detector SPECT scanner or a rotating gamma camera. In normal subjects, early
      SPECT images demonstrated uniform distribution of radioactivity in the cerebral
      gray matter and cerebellum reflecting regional cerebral blood flow, whereas late
      SPECT images showed high radioactivity only in the basal ganglia. All the
      patients with Parkinson's disease also demonstrated symmetrical basal ganglia
      uptake in the late SPECT images, but it was diminished in parkinsonism and
      Wilson's disease. One patient with a growth hormone-producing pituitary tumor had
      a positive uptake in the tumor. These preliminary clinical data demonstrated that
      2'-ISP can be used for SPECT imaging of D2 dopamine receptors and may be of
      clinical value for the diagnosis and planning of the treatment of neurological
      diseases.

PMID- 8534586
TI  - Brain uptake and metabolism of [1-11C]octanoate in rats: pharmacokinetic basis
      for its application as a radiopharmaceutical for studying brain fatty acid
      metabolism.
AB  - The uptake of octanoate in rat brain and its metabolism were investigated by
      means of intravenously injecting [1-11C] or [1-14C]octanoate as a tracer. The
      radioactivity in the cerebrum was increased by an injection of [1-11C]octanoate,
      and reached its peak level (0.33% ID/g) in about 2 to 5 min, and then decreased
      slowly. The cerebrum-to-blood ratio of the radioactivity increased with time over
      a period of 30 min. At 30 sec, [1-11C]octanoate that remained unchanged in the
      cerebrum accounted for only 8% of the total radioactivity, in spite of there
      being about 90% in the blood. By means of an injection of [1-14C]octanoate, more
      than 70% of the total radioactivity in the cerebrum was found to be attributable
      to radiolabeled glutamate and glutamine at each time point measured between 30
      sec and 30 min. The results show that [1-11C]octanoate enters rat brain easily
      and is trapped in the cerebrum, probably in the form of glutamate and glutamine,
      and the usefulness of [1-11C]octanoate as a radiopharmaceutical for studying
      brain fatty acid metabolism by positron emission tomography is therefore
      suggested.

PMID- 8534587
TI  - Incidental detection of breast cancer during T1-201 myocardial SPECT study.
AB  - A case of left breast cancer which was detected incidentally by T1-201 SPECT
      performed to evaluate the status of myocardial perfusion, is reported. Both
      stress and redistribution T1-201 SPECT clearly delineated the tumor. It was
      confirmed later as scirrhous carcinoma of the breast.

PMID- 8534588
TI  - The value of combined 99mTc-Sn-colloid and 99mTc-RBC scintigraphy in the
      evaluation of a wandering spleen.
AB  - Wandering spleen is the term commonly applied to splenic hypermobility that
      results from laxity or maldevelopment of its suspensory ligaments. It comes to
      medical attention usually as an abdominal mass, or when the spleen undergoes
      torsion. Diagnosis on clinical grounds alone is rarely made, and ultrasonography,
      CT and MRI findings have no specific characteristics for this condition. 99mTc
      labeled colloid taken up by the spleen may provide a specific diagnosis. We
      report a case of wandering spleen, in which the preoperative diagnosis was made
      on the basis of sequential liver-spleen scintigraphy with 99mTc-Sn-colloid and
      blood-pool scintigraphy with 99mTc-RBC. This is a rare case, in which
      hypermobility was assessed by sequential 99mTc-Sn-colloid scintigraphy, and to
      our knowledge, is the first case in which 99mTc-RBC scintigraphy provided useful
      information on splenic blood volume and its location.

PMID- 8534589
TI  - 111In-octreotide scintigraphy: a tool to select patients with endocrine
      pancreatic tumors for octreotide treatment?
AB  - The results of octreotide scintigraphy, performed in two patients with malignant
      endocrine pancreatic tumors, were compared with the effect of somatostatin-14 and
      its analogue octreotide on hormonal levels and clinical outcome. Radiolabeled
      octreotide failed to demonstrate any tumor localisation in a patient with a
      malignant insulinoma. Nevertheless, IV injection of somatostatin and octreotide
      resulted in a significant decrease in peripheral insulin levels. Moreover in this
      patient, chronic treatment with a high dose of octreotide subcutaneously was able
      to transiently lower the incidence of hypoglycemic events. In a second patient
      with metastatic PP-oma, 111In-octreotide disclosed a pancreatic tumor in the tail
      of the pancreas and metastatic supraclavicular lymph nodes. In this patient IV
      administration of somatostatin and octreotide inhibited the hormonal secretion of
      the tumor but subcutaneous injection of octreotide induced hardly any decrease in
      plasma PP levels and failed to affect tumor growth. These observations find a
      possible reason for this in the heterogeneous affinity of the somatostatin
      receptors in endocrine pancreatic tumors. They indicate that octreotide
      scintigraphy alone should not be used to select patients with neuroendocrine
      tumors who can benefit from chronic treatment with the somatostatin analogue.

PMID- 8534590
TI  - Uptake of pentavalent technetium-99m dimercaptosuccinic acid in idiopathic
      synovial chondromatosis.
AB  - We reported two Tc-99m(V) DMSA scintigrams in patients with idiopathic synovial
      chondromatosis which affected the metacarpo-phalangeal joint and shoulder joint.
      Tc-99m(V) DMSA accumulated markedly and diffusely in the tumor. Tc-99m(V) DMSA
      scintigraphy would be valuable for deciding the optimal site for biopsy.

PMID- 8534591
TI  - Tc-99m sestamibi scanning in the preoperative localization of mediastinal
      parathyroid adenomas.
AB  - We report on two patients with mediastinal parathyroid adenomas who underwent
      preoperative Tc-99m sestamibi scintigraphy. Excellent physical characteristics of
      technetium and slow washout of Tc-99m sestamibi made possible clear delineation
      of mediastinal parathyroid adenomas by Tc-99m sestamibi imaging.

PMID- 8534593
TI  - Dracunculiasis.

PMID- 8534592
TI  - Discrepant 99mTc-ECD images of CBF in patients with subacute cerebral infarction:
      a comparison of CBF, CMRO2 and 99mTc-HMPAO imaging.
AB  - Three patients with subacute ischemic cerebral infarction examined by SPECT with
      99mTc-ECD and PET within the same day showed signs of luxury perfusion in the
      subacute phase, which is between 9 to 20 days after the onset. A 99mTc-HMPAO
      SPECT study was also performed within 2 days of the ECD-SPECT study. ECD-SPECT
      images of three patients displayed a focal decreased uptake in the infarcted
      lesions, while in infarcted foci, there was almost equivalent or increased CBF
      compared to normal and unaffected areas, decreased CMRO2, and high HMPAO uptake.
      The ECD-SPECT results were similar to those of CMRO2 rather than CBF, though the
      HMPAO-SPECT image was similar to that of CBF. In one patient, HMPAO images
      revealed hyperfixation of the tracer. In the chronic phase and in the acute phase
      before 5 days after the onset, there were no discrepancies among the ECD-SPECT,
      CBF, HMPAO-SPECT, and CMRO2 images. These observations indicated that 99mTc-ECD
      is a good indicator of damaged brain tissues in subacute ischemic infarction.
      They also suggested that 99mTc-ECD is a potential agent with which to evaluate
      cerebral tissue viability in some pathological states of cerebrovascular disease.
      The characteristics may be suitable for confirming the effects of thrombolytic
      therapy in acute ischemia, because these conditions often show signs of luxury
      perfusion when the therapy is successful.

PMID- 8534594
TI  - Global Programme for Vaccines and Immunization. Vaccine research and development.

PMID- 8534595
TI  - Lyme disease 1994.

PMID- 8534596
TI  - Leptospirosis identified in Nicaragua.

PMID- 8534597
TI  - Expanded programme on immunization. Progress towards poliomyelitis eradication,
      WHO Eastern Mediterranean Region, 1988-1994.

PMID- 8534598
TI  - CME in oncology--from where we were to where we are going.

PMID- 8534599
TI  - Interactive computer-based programs for a cancer learning center.
AB  - This paper describes the design and evaluation of a computer-based instruction
      (CBI) program that was integrated into a multidisciplinary cancer curriculum at
      the Medical College of Pennsylvania. Instruction took place in a cancer learning
      center. Modules contained literature, posters, slide sets, videocassette films,
      and "see, touch, and feel" models to teach and practice breast, testicular,
      rectal, laryngeal, and colonoscopic examinations. The CBI (programmed on
      HyperCard) contained tutorials divided into three levels of learning objectives:
      level one, epidemiology and prevention; level two, diagnosis and staging; and
      level three, management and prognosis. Simulated cases and test items were
      developed for each level. To evaluate students' perceptions of the program and
      provide them with feedback about their performances, the authors designed a
      questionnaire, held a focus group, and developed a built-in tracking system for
      the CBI. Results showed that the program was well received, the students answered
      the test items correctly, and the students wanted more time to study cancer. A
      description of some of the problems encountered with technology and equipment is
      provided for faculty who may be interested in designing and implementing similar
      CBI programs.

PMID- 8534600
TI  - Using the hypertext software to develop computer-assisted instruction in oncology
      for medical students.
AB  - A new development in computer-assisted medical education has been the
      introduction of hypertext authoring systems. Authoring systems are computer
      programs that can allow an instructor to prepare computer-based medical
      educational materials without the need to know programming languages. Hypertext
      is a database management system that lets the user connect screens of information
      using associative links. The authors developed a hypertext authoring system for
      teaching their medical students the domain of oncology. The features of the
      system are hierarchical structure, index browsing, and nonsequential browsing.
      Moreover, the student may become a writer of a hyperdocument by typing a few
      script commands. In this way the hierarchical structure of a document meets the
      needs of the reader. Although hypertext brings with it a few difficulties for the
      student, the authors expect that the system will become a popular mean for
      organizing textual information for retrieval and browsing in oncology.

PMID- 8534601
TI  - Psychosocial effects of level of information and severity of disease on head-and
      neck cancer patients.
AB  - This study examined the psychosocial effects of levels of information available
      to patients and compared them with those of disease severity. A questionnaire
      with multiple-choice and open-ended questions assessing quality of life in
      various domains (e.g., fears and worries, functioning in the family) and scales
      assessing anxiety, anger, and depression were administered to patients and their
      partners or closest relatives. The subjects were 55 head-and-neck cancer patients
      (40 men and 15 women) in disease stages I to IV, grades of tumors G1 to G3-4,
      with disease durations ranging from three months to 21 years. They were divided
      into three groups on the basis of the amounts of information they had about their
      disease and prognosis, and again on the basis of disease severity, based on
      stages and patients' evaluations. The numbers of psychosocial variables
      differentiating significantly between the groups deviated significantly from
      chance in both groupings. The results showed more effects for information than
      for disease severity. The highly informed were better adjusted in interpersonal
      relations and had more intimacy with family, but had more fears, anxiety, changes
      in their lives, worries about health, and concern with physical symptoms. The
      reports of partners were fewer and lent some support to those of patients.
      Disease severity affected mostly fears, anxiety, and worries about health.

PMID- 8534602
TI  - Mammography usage and knowledge about breast cancer in a Michigan farm population
      before and after an educational intervention.
AB  - The purpose of this study was to identify factors associated with the use of
      mammography screening in a farm population, before and after a community-based
      educational intervention. The educational intervention included sending
      individual mailings containing information about breast cancer risk and community
      sources for screening, and providing information and screening at local county
      fairs and agricultural community fairs. The authors used multivariate analytic
      methods to analyze the responses, reported by 1,545 women, to discern the roles
      of sociodemographic, attitudinal, and knowledge variables in this population's
      breast cancer screening practices. Results showed that the rural participants in
      both the intervention and the control communities demonstrated significant
      changes in knowledge and attitudes about breast cancer. Mammography usage was
      significantly higher among women who had higher scores on the knowledge and
      awareness assessments. Education--rather than income, insurance coverage, or
      family history of breast cancer--emerged in multivariate analyses as the most
      significant predictor of knowledge and awareness score levels associated with
      greater use of mammography. Implications of this study include support for
      education that emphasizes the benefits of early detection of breast cancer for
      all women.

PMID- 8534603
TI  - Breast self-examination among Swedish women: a survey of frequency, knowledge,
      and attitudes.
AB  - Breast cancer is a common cause of death among women. The aim of this study was
      to determine whether women carry out regular breast self-examination (BSE), and
      to describe their knowledge of, and attitudes towards, breast cancer.
      Questionnaires were mailed to 200 randomly selected women who had not undergone
      breast cancer surgery. The response rate was 81%. The respondents were divided in
      three groups: those who practiced BSE regularly, those who practiced BSE
      occasionally, and those who did not practice BSE. The results show that only 10%
      of the sample practice BSE. Neither age, educational background, nor occupation,
      nor having knowledge of breast disease and medical outcome was associated with
      BSE practice. Nor did having a close relative or friend with breast cancer affect
      the practice of BSE.

PMID- 8534604
TI  - A cancer-prevention intervention for disadvantaged women: design and
      implementation.
AB  - A cancer-prevention mini-course was designed to increase knowledge about breast
      and cervical cancers as well as to improve attitudes and behaviors regarding
      preventive health care among minority and medically underserved women. The
      culturally-sensitive two-hour psycho-educational intervention was developed as an
      interactive curriculum in English- and Spanish-language versions for home health
      care attendants. After development and piloting, the course was offered as part
      of the weekly 40-hour training program for home attendants in Bronx, New York.
      After six months it was offered as in-service training for home attendants
      employed by a licensed home attendant-training agency. The home attendants who
      participated in the mini-course were primarily Hispanic (62%) and black (31%).
      Results of evaluation indicate that the mini-course has been remarkably
      successful in achieving its goals. Primary measures of its success include: 1)
      integration of the mini-course into the settings in which it is being offered; 2)
      student participation, absorption of material, and enthusiasm for the course. The
      mini-course has been successfully incorporated into the training agencies, with
      strong staff commitment to the program. Participants evince high levels of
      enthusiasm for the class, reporting that they have learned new information and
      have especially enjoyed the interactive nature of the class. Though the
      development of this cancer-prevention mini-course (and its materials) as well as
      integrating it into appropriate settings required a substantial investment of
      time and resources, now that it is developed, the intervention proves to be
      efficient and effective, and is meeting a large need.

PMID- 8534605
TI  - On mentoring.

PMID- 8534606
TI  - The life situation of cancer patients in an oncology department.

PMID- 8534607
TI  - Facing the truth: elder abuse [continuing education credit].

PMID- 8534608
TI  - Expression of endoglin in psoriatic involved and uninvolved skin.
AB  - Endoglin is a glycoprotein with TGF-beta binding capacity and is predominantly
      expressed on endothelial cells. In psoriasis, TGF-beta has appeared to play a
      role in the extravasation of peripheral blood mononuclear cells via the
      endothelium. In order to find out more about the role of endoglin in psoriasis,
      immunohistochemical staining with PN-E2, a novel anti-endoglin, and of PAL-E,
      recognizing vascular endothelium, was carried out in psoriatic involved,
      psoriatic uninvolved and normal skin. The expression of the antigens was assessed
      semi-quantitatively using a five-point scale. In psoriatic involved skin, a high
      endoglin expression was found. In psoriatic uninvolved skin, however, we found
      that endoglin expression was significantly decreased compared with normal skin.
      The relevance of these findings to the pathogenesis of psoriasis is discussed.

PMID- 8534609
TI  - Perifollicular clear space under skirt-like epithelial structure of human small
      vellus hair follicle.
AB  - Human hair follicles, especially small vellus hair follicles, showed
      characteristic structures as follows: (I) small vellus hair follicles were
      surrounded with skirt-like epithelial structures or perifollicular connective
      tissue capsule; (II) perifollicular clear space was present between the outer
      root sheath and skirt-like structure, or the outer root sheath and perifollicular
      connective tissue capsule; (III) perifollicular clear space was filled with a
      loose, alcian blue positive mucinous substance and elongated fibroblasts and mast
      cells; (IV) perifollicular nerve endings were attached to the follicular wall in
      a palisading arrangement within the clear space under the skirt; (V)
      perifollicular nerve end organs and connective tissue capsule were positively
      immunostained for CD34 and protein gene product 9.5 (PGP9.5). These specialized
      structures of human small vellus hair follicles seem to correspond to the blood
      sinus of the sinus hair follicles, where similar structural elements were found.

PMID- 8534610
TI  - Purification of human blood eosinophils by a combination method using anti-CD16
      monoclonal antibody, immunobeads, and Nycodenz density gradient.
AB  - A simple method is described for the procurement of human blood eosinophil
      phenotypes by combining an anti-CD16 monoclonal antibody, immunobeads, and a non
      toxic and non-ionic density gradient medium, Nycodenz. The purification depends
      on the removal of mononuclear cells using a 1.076/1.102 g/ml Nycodenz density
      gradient, partial removal of neutrophils based on different binding to plastic
      dishes, interaction of residual neutrophils with immunobeads via an anti-CD16
      monoclonal antibody and, finally, extraction of eosinophil phenotypes by sifting
      the immunobeads-loaded neutrophils through an 1.080/1.102 g/ml Nycodenz density
      gradient. This method permits simultaneous preparation of highly purified
      normodense (> 1.080 g/ml) and hypodense eosinophils (< 1.080 g/ml) with
      reasonable chemiluminescence responses to opsonized zymosans and helminthotoxic
      activity to opsonized schistosomula corresponding to their own immunocytological
      properties.

PMID- 8534611
TI  - The effects of cyclosporin A and FK506 on proliferation and IL-8 production of
      cultured human keratinocytes.
AB  - The present study was conducted to determine whether cyclosporin A (CsA) and
      FK506 could be effective in inhibiting the proliferation and cytokine secretion
      of normal human epidermal keratinocytes (NHEK). NHEK proliferation in the
      presence of CsA and FK506 at the concentrations 10(-9) to 10(-5) M at 24 and 48 h
      time points was measured colorimetrically by the MTS assay. CsA had inhibitory
      effects from 10(-6) to 10(-5) M, while FK506 had no effect, except for toxicity
      at the very highest concentrations (5 x 10(-6) M and higher). NHEK cells
      spontaneously secrete IL-8 (243.4 +/- 55.5 pg/ml), and this baseline level was
      augmented by TNF-alpha alone, or synergistically by TNF-alpha and IFN-gamma,
      which are thought to be secreted by T cells. Neither CsA nor FK506 had any
      significant effect on either spontaneous or cytokine-stimulated keratinocyte IL-8
      production. Therefore, it is most likely that the two drugs indirectly inhibit
      the keratinocyte inflammatory response through their actions on T cells or other
      immunocompetent cells.

PMID- 8534612
TI  - Disaccharide analysis of the skin glycosaminoglycans in chronically ultraviolet
      light-irradiated hairless mice.
AB  - The alteration of main disaccharide units in the skin of hairless mice (HOS:Hr 1)
      after chronic and repeated ultraviolet light (UV) radiation was investigated
      using high performance liquid chromatography after labeling with 1-phenyl-3
      methyl-5-pyrazolone. The total amount of main disaccharide units increased by UVA
      irradiation at the 24th and 36th weeks in comparison with the control. At the
      36th week UVA significantly increased hyaluronic acid-derived delta Di-HA (HA).
      Dermatan sulfate-derived delta Di 4S (DS) and chondroitin sulfate-derived delta
      Di-4S (CS) increased at the 36th week, although not statistically significant.
      The total amount of main disaccharide units was increased significantly by UVB
      irradiation at the 24th week as compared with the control. Concerning the
      compositional change in main disaccharide units after a 36-week repeated
      exposure, the decrease in delta Di-HA(HA) and the increase in delta Di-4S (DS)
      were found in the order of control, UVA- and UVB-irradiated groups. These
      results, for the first time, indicate the precise alterations of
      glycosaminoglycans, both in the total amount and in the composition, confirming
      the previous histochemical findings. This disaccharide analysis should provide a
      useful method to examine the biochemical changes of skin glycosaminoglycans in
      photoaging.

PMID- 8534613
TI  - Elevation of serum-soluble E-selectin in atopic dermatitis.
AB  - Atopic dermatitis (AD) is characterized by alterations in cellular and humoral
      immunity. The objective of this study is to determine whether soluble E-selectin
      (sE-selectin) plays a role in AD. We examined the serum sE-selectin levels in
      patients with atopic dermatitis (n = 23), patients with urticaria (n = 9), and
      normal healthy individuals (n = 15). The severity of the disease in the AD
      patients was graded using an established clinical scoring system. We found that
      sE-selectin levels were significantly higher in atopic dermatitis than in
      urticaria (P < 0.001) or normal controls (P < 0.0001). In addition, there was a
      significant correlation between serum sE-selectin and the clinical score (R =
      0.73, P < 0.0001). Clinical improvement was associated with a decrease in both
      the clinical score (P < 0.01) and serum sE-selectin (P < 0.01). E-selectin was
      recognized on the vascular endothelial cells of the erythematous lesions of AD
      patients. These results indicate that sE-selectin may play a role in AD.

PMID- 8534614
TI  - Effect of RU 486 on the atrophogenic and antiinflammatory effects of
      glucocorticoids in skin.
AB  - Clobetasol-17-propionate (CP), a synthetic glucocorticoid (GC), reduced skin
      thickness in rats. Both the subcutaneous injection and topical applications of RU
      486 counteracted CP-induced reduction in skin thickness. Topical application of
      the CP cream completely inhibited the ear edema produced by croton oil. A less
      potent GC, hydrocortisone-17-butyrate, also inhibited ear edema. This
      antiinflammatory effect was not abolished by the subcutaneous injection or
      topical application of RU 486. These observations suggest that GC-induced skin
      atrophy is mediated by glucocorticoid receptors (GRs), while the inhibition of
      croton oil-induced inflammation by GC is primarily related to the direct effects
      of GC, which are not mediated by GRs. Our findings suggest that RU 486 inhibits
      the atrophogenic effect of GCs without interfering with their antiinflammatory
      effect. Dissociation of antiinflammatory and atrophogenic activity of GC seems
      favorable in treating inflammatory skin diseases lacking epidermal proliferation.

PMID- 8534615
TI  - A study of skin responses to follow-up, rechallenge and combined effects of
      irritants using non-invasive measurements.
AB  - Irritant contact dermatitis is a common clinical problem. Primary irritation can
      be easily recognized, but cumulative irritation by daily exposure is hard to be
      diagnosed and the condition may fail to be clear even away from work. The
      mechanism of irritant dermatitis produced by repeated or combined exposure to
      clinical or subclinical doses of irritants is still poorly understood. In order
      to find out whether the subclinical doses of irritants affect each other by
      repeated or combined exposure according to their concentrations, non-invasive
      measurements, transepidermal water loss and laser Doppler flowmetry were used.
      Sodium lauryl sulfate, sodium hydroxide and benzalkonium chloride were serially
      diluted and patch-tested with large Finn chambers on Scanpor tape on the back of
      normal human volunteers and responses were followed up for 7 days. Twice repeated
      exposure with subclinical doses of irritants at 1 day intervals were also
      performed. Repeated daily applications for 5 days with subclinical doses of
      single or premixed irritants were performed to know the combined irritating
      effect. The irritant response was well correlated to the concentration of the
      irritants. However, increased response was not observed when subclinical doses
      were rechallenged on the previously patch tested sites. Twice-repeated exposure
      of subclinical doses of irritants increased skin irritancy when measured by
      transepidermal water loss and laser Doppler flowmetry. Some correlation and some
      discrepancies were observed between different evaluation methods in combined and
      repeated application tests with irritants of subclinical doses. Responses of skin
      irritancy induced by subclinical doses showed somewhat different pattern from
      that given strong irritants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534616
TI  - Memory T lymphocytes' adherence to interferon gamma-activated human dermal
      microvascular endothelial cells via E-selectin.
AB  - The regulation of leukocytes-endothelial cells binding by biological response
      modifiers have an important role in determining the progression of acute and
      chronic inflammatory responses. In order to define the influence of E-selectin on
      the binding of T lymphocytes to human dermal microvascular endothelial cells
      (HDMEC), we examined the cell surface expression of E-selectin on HDMEC and the
      regulation of the binding of T lymphocytes to HDMEC by IFN-gamma. We have
      demonstrated that stimulation of HDMEC with IL-1 alpha or TNF alpha leads to
      transient E-selectin induction which disappears after 48 h, but stimulation of
      HDMEC with IFN-gamma resulted in delayed E-selectin induction which was seen at
      48 h of incubation and persisted until 72 h after stimulation. However,
      stimulation with IFN-gamma failed to induce E-selectin expression on human
      umbilical vein endothelial cells. The delayed E-selectin expression on HDMEC by
      IFN-gamma coincided with the increases in T lymphocyte binding to IFN-gamma
      activated HDMEC. The binding of memory T lymphocytes to IFN-gamma-activated HDMEC
      was greater than that of naive T lymphocytes. Anti-E-selectin antibody partially
      inhibited memory T lymphocyte binding to HDMEC after 48 h of stimulation with IFN
      gamma. These data show that E-selectin expressions by IFN-gamma on endothelial
      cells are regulated in a tissue-specific fashion and that E-selectin may be
      important in vivo in the preferential migration of memory T lymphocytes into
      inflammatory sites in the skin.

PMID- 8534617
TI  - Randomised trials and the British Journal of Obstetrics and Gynaecology. Minimum
      requirements for publication.

PMID- 8534618
TI  - Bromocriptine and postpartum lactation suppression.

PMID- 8534619
TI  - Nutrition of the preterm baby.

PMID- 8534620
TI  - Low dose aspirin in pregnancy and early childhood development: follow up of the
      collaborative low dose aspirin study in pregnancy. CLASP collaborative group.
AB  - OBJECTIVE: To determine any benefits or risks, expressed in early childhood, of
      low dose aspirin treatment in pregnancies at high risk of complications due to
      pre-eclampsia or intrauterine growth retardation. DESIGN: A questionnaire-based
      follow-up at 12 and 18 months of age of cohorts of surviving children whose
      mothers participated in a large randomised, double-blind placebo-controlled trial
      of 60 mg aspirin. SETTING: United Kingdom and Ottawa, Canada. SUBJECTS: 4168
      children assessed at 12 months through information provided by general
      practitioners, and 4365 assessed at 18 months through a questionnaire to parents.
      MAIN OUTCOME MEASURES: Hospital visits in the first 18 months for congenital
      malformations, motor deficit, developmental delay, respiratory problems or
      bleeding problems; height or weight below the third centile; and delayed
      acquisition of certain developmental skills. RESULTS: There were no clear
      differences in any of the main outcome measures, although some confidence
      intervals were wide. CONCLUSIONS: Although an adverse effect can not be ruled
      out, these findings are reassuring about the safety of low dose aspirin started
      after the first trimester, at least in respect of congenital malformations, major
      motor deficit, and severe neuromotor or developmental delay identifiable in early
      childhood. They provide no clear evidence of benefit. Taking into account
      evidence from large randomised controlled trials, the place of low-dose aspirin
      in pregnancy appears to be limited, although it may be beneficial for women at
      high risk of early onset pre-eclampsia; for them, evidence suggesting that it is
      not harmful is important.

PMID- 8534621
TI  - The European Collaborative Study: clinical and immunological characteristics of
      HIV 1-infected pregnant women.
AB  - OBJECTIVE: To describe the changing clinical and immunological characteristics
      and timing of diagnosis of HIV-infected pregnant women enrolled in the European
      Collaborative Study. DESIGN: A prospective study of the mothers of children
      enrolled in the European Collaborative Study on children born to HIV-infected
      women. SETTING: Twenty-one European centres in seven countries. SUBJECTS: One
      thousand six hundred and ninety HIV-infected women and their 1754 deliveries.
      RESULTS: The proportion of women in whom HIV infection had been diagnosed before
      pregnancy increased significantly over time, from 7% in 1984-1985 to 65% in 1994
      (P < 0.001). The prevalence of breastfeeding, which was related to the timing of
      diagnosis, significantly declined over the study period. The mean CD4 count was
      510 cells/mm3, and there was a significant decline in average CD4 count over the
      study period. Black women had a significantly lower CD4 count than white women.
      From survival analysis it is estimated that five years after delivery 14% of
      women will have died and 24% will have developed CDC stage IV disease.
      CONCLUSIONS: Timing of diagnosis is of critical importance if mother-to-child
      transmission is to be reduced through avoidance of breastfeeding and zidovudine
      therapy and effective antenatal screening policies have become increasingly
      important. The rate of progression of maternal disease highlights the
      implications of HIV infection for their children, both infected and uninfected.

PMID- 8534622
TI  - Blood pressure and renal function seven years after pregnancy complicated by
      hypertension.
AB  - OBJECTIVE: To assess the occurrence of chronic hypertension and renal disorder
      after gestations complicated by pregnancy induced hypertension or pre-eclampsia
      and to define background factors and laboratory analyses at follow up examination
      which discriminate between women who remain normotensive and those who develop
      hypertension. SETTING: Swedish university hospital. SUBJECTS: Women with
      pregnancy induced hypertension (PIH) (n = 49), pre-eclampsia (n = 45) or a
      normotensive pregnancy (n = 44) during 1986. DESIGN: Subjects were reviewed in
      1993 with regard to chronic hypertension and renal disorder. Plasma
      concentrations of creatinine, urea, uric acid, calcium and albumin were measured,
      and urine was examined for the presence of microalbuminuria and erythrocyte
      excretion rate. Those with and without hypertension at follow up were compared
      with regard to the renal function tests and possible features in the history
      which might predict chronic hypertension. RESULTS: Women with a history of
      pregnancy induced hypertension or pre-eclampsia had an increased risk, relative
      to controls, for hypertension at follow up (37% and 20% vs 2%; P < 0.001),
      microalbuminuria (14% and 20% vs 2%; P < 0.05) and demonstrated increased plasma
      levels of albumin corrected calcium (2.41 [SE 0.02] and 2.40 [0.01] vs 2.32
      [0.01] mmol/l; P < 0.001). The only factors significantly associated with
      hypertension at follow up were the presence of microalbuminuria (P = 0.0008) and
      having had a delivery prior to the index pregnancy (P = 0.0017). CONCLUSIONS: The
      risk for chronic hypertension seven years after a pregnancy complicated with
      pregnancy induced hypertension or pre-eclampsia is considerably increased. The
      presence of hypertension at follow up is closely related to residual renal
      disorder.

PMID- 8534623
TI  - Effect of preterm premature rupture of membranes on neurodevelopmental outcome:
      follow up at two years of age.
AB  - OBJECTIVE: To evaluate the impact of preterm premature rupture of membranes on
      the neurodevelopmental outcome of infants, assessed at two years of age. DESIGN:
      A prospective observational study of surviving preterm infants born after
      premature rupture of membranes and of infants born after spontaneous preterm
      labour with intact membranes. The study was carried out in the period 1986 to
      1991. SETTING: Pavia, Italy. SUBJECTS: One hundred and forty singleton infants
      born prematurely after premature rupture of membranes between 24 and 34 weeks of
      gestation and 120 controls of similar gestational age born after spontaneous
      preterm labour with intact membranes. MAIN OUTCOME MEASURES: Infant
      neurodevelopmental outcome at two-year follow up. RESULTS: After adjustment, by
      logistic analysis for the effect of gestational age and birthweight, infants born
      after premature rupture of membranes were more likely to have severe
      neurodevelopmental impairment (spastic tetraplegia and/or Bayley mental
      developmental index < 71) than controls (adjusted OR 5.75, 95% CI 1.22-27.18).
      Multivariate analysis of linear trend showed a statistically significant relation
      of duration of membrane rupture to occurrence of severe intraventricular
      haemorrhage, cystic periventricular leucomalacia and moderate to severe infant
      neurodevelopmental impairment. CONCLUSION: Infants born after prolonged premature
      rupture of membranes are at higher risk of subsequent moderate to severe
      neurodevelopmental impairment than those born after spontaneous labour with
      intact membranes.

PMID- 8534624
TI  - Longitudinal study of fetal middle cerebral artery flow velocity waveforms
      preceding fetal death.
AB  - OBJECTIVE: To assess longitudinally fetal cerebral vasodilatation in small-for
      gestational age fetuses to investigate whether intrauterine death might be
      predictable. DESIGN: Prospective observational study. SETTING: Ultrasound
      department in a university hospital. SUBJECTS: Five pregnancies with
      ultrasonographically confirmed small fetuses (abdominal circumference less than
      the 3rd centile) monitored longitudinally until time of intrauterine death. MAIN
      OUTCOME MEASURE: Time between last ultrasound examination and diagnosis of
      intrauterine death, and variation in middle cerebral artery pulsitility index
      prior to death. RESULTS: Two of the five fetuses showed a reversal of adaptation
      (as indicated by an elevation of the middle cerebral artery pulsitility index)
      within 48 hours of intrauterine death. The other three had their final ultrasound
      examination 3 to 7 days before death and showed no such reversal of adaptation.
      CONCLUSION: Reversal of adaptation in fetal hypoxaemia as indicated by a rise in
      the middle cerebral artery pulsitility index may be a predictor of intrauterine
      death within 48 hours. Whether delivery after reversal of adaptation would result
      in salvage of neurologically intact babies needs to be investigated.

PMID- 8534625
TI  - Lack of evidence for a circadian rhythm of IGFBP-1 in the mother and fetus during
      labour.
AB  - OBJECTIVE: To determine whether the circadian rhythm of circulating levels of
      insulin-like growth factor binding protein-1 (IGFBP-1) is evident at the time of
      delivery. DESIGN: Prospective observational study in six pregnant women and cross
      sectional study in 65 women at the time of delivery. SUBJECTS: Six pregnant women
      sampled over a period of 24 hours, 23 women sampled at the time of elective
      caesarean section, and 42 women sampled at the time of vaginal delivery. RESULTS:
      In the women sampled serially over a 24 hour period there was an obvious
      circadian rhythm of IGFBP-1 with a peak between 01.00 and 09.00 hours. In the
      women sampled at the time of delivery there was no evidence for any relationship
      between the time of delivery and maternal or fetal levels of IGFBP-1.
      CONCLUSIONS: The circadian rhythm of IGFBP-1 is not observed in women in labour.
      Therefore, the time of day is not an important confounding variable in studies on
      IGFBP-1 levels at the time of normal delivery.

PMID- 8534626
TI  - Scalp blood lactate: a new test strip method for monitoring fetal wellbeing in
      labour.
AB  - OBJECTIVE: To determine fetal scalp blood lactate with a new test strip method in
      parturients with normal and abnormal cardiotocograms during labour and to
      describe the relation to maternal lactate, fetal scalp blood pH, cord artery
      lactate and acid-base balance. SETTING: Labour wards at the University Hospitals
      of Huddinge and Lund and at the County Hospital of Ostersund, Sweden. MATERIALS
      AND METHOD: Fetal scalp blood was sampled for lactate (n = 269) and pH (n = 285)
      determination in 177 parturients with abnormal intrapartum CTG. Lactate and pH
      were also analysed in a group of 64 women with normal pregnancies and with a
      reactive fetal heart rate tracing prior to sampling of fetal scalp blood. At
      fetal blood sampling lactate was also determined in maternal capillary blood,
      while at birth lactate and acid-base balance in cord artery blood was performed
      in almost all cases. MAIN OUTCOME MEASUREMENTS: Medians and percentiles (lactate
      and acid-base balance). Correlation between fetal scalp blood lactate (dependent)
      and scalp blood pH, cord artery blood lactate and acid-base parameters and labour
      time prior to fetal blood sampling. RESULTS: In the group with abnormal
      cardiotocograms, fetal scalp and umbilical artery blood lactate and acid-base
      parameters differed significantly from the same parameters in the normal group.
      The fetal-maternal lactate gradient changed from negative in the normal group to
      positive in the fetal distress group. Multiple regression analysis, with scalp
      lactate as the dependent parameter, revealed a significant correlation with fetal
      scalp blood pH (P < 0.001) and umbilical artery lactate (P < 0.01). CONCLUSIONS:
      Intrapartum scalp blood lactate was significantly correlated with pH and cord
      artery lactate. The results indicate that increased lactate levels in fetal blood
      sampling describes fetal lactacidosis. The new disposable test strip requiring
      only 5 microliters of blood for lactate determination may be better than
      traditional methods for monitoring fetal wellbeing in labour.

PMID- 8534627
TI  - Hypertensive and normal pregnancy: a longitudinal study of blood pressure,
      distensibility of dorsal hand veins and the ratio of the stable metabolites of
      thromboxane A2 and prostacyclin in plasma.
AB  - OBJECTIVE: By combining serial measurements of the circulating concentrations of
      thromboxane A2 and prostacyclin with measurements of venous distensibility (taken
      during the pregnancies of both normal women and those with pregnancy induced
      hypertension or pre-eclampsia), to test the following hypotheses: 1. that changes
      in the venous plasma ratio of thromboxane (TXB2) and 6-keto-PGF1 alpha would
      correlate with changes in the blood pressure of women developing and recovering
      from pregnancy induced hypertension or pre-eclampsia and 2. that changes in
      venous distensibility would correlate with changes in arterial blood pressure in
      pregnancy induced hypertension or pre-eclampsia. DESIGN: Prospective,
      longitudinal cohort study. SETTING: John Hunter Hospital clinic, Newcastle,
      Australia. SUBJECTS: One hundred and sixty primiparous women, recruited when
      presenting for their first routine antenatal visit, were investigated at, or
      close to, 19, 28 and 37 weeks of gestation; a subgroup was also studied in the
      postnatal period. The measurements of the patients who developed pregnancy
      induced hypertension or pre-eclampsia were compared with those of controls
      selected from the cohort. MAIN OUTCOME MEASURES: Serial measurements of the
      circulating concentrations of the stable metabolites of thromboxane A2 and
      prostacyclin (TXB2 and 6-keto-PGF1 alpha, respectively), venous distensibility
      and immediate (no rest) and resting (for at least 30 min) blood pressures.
      RESULTS: There was no significant difference between the subject and control
      groups at any time during or after the pregnancy in the concentrations of
      prostaglandin metabolites, their ratio or venous distensibility. In contrast,
      there was a significant difference between the groups at 19 weeks for immediate
      and resting readings of diastolic pressure (6 mmHg (95% CI 1.5 to 10.5) and 4
      mmHg (95% CI 0.1 to 7.9), respectively). These differences increased through the
      pregnancy but mean postnatal readings for the groups were almost identical
      suggesting that the subjects were not intrinsically hypertensive compared with
      controls. Blood pressures for the subject group, both immediate and resting, were
      significantly different from the 19 week readings at 28 weeks (diastolic) and at
      37 weeks (systolic and diastolic). The only significant change from first
      readings among controls was in postnatal systolic pressure which was
      significantly higher than 19 week values, probably reflecting the vasodilatation,
      with accompanying hypotension, of early, normal pregnancy. This difference was
      not observed in those who subsequently developed pregnancy induced hypertension
      or pre-eclampsia. CONCLUSIONS: Our study was unable to demonstrate differences in
      circulating metabolites or venous distensibility between normotensive women and
      those with pregnancy induced hypertension or pre-eclampsia. If pregnancy induced
      hypertension or pre-eclampsia in humans represents not so much the presence of
      abnormal constrictor influences as a process initiated by failure of normal
      vasodilatation in early pregnancy, studies carried out later may detect mainly
      adaptive and secondary changes.

PMID- 8534628
TI  - Receptor-mediated uterine effects of vasopressin and oxytocin in nonpregnant
      women.
AB  - OBJECTIVE: To study in nonpregnant women myometrial actions of vasopressin and
      oxytocin and the involvement in these effects of specific uterine receptors.
      SUBJECTS: Twenty-eight women undergoing hysterectomy for benign gynaecological
      disorders. INTERVENTIONS: Intrauterine pressure recordings. Intravenous bolus
      injections of 10 pmol/kg body weight of vasopressin and oxytocin. Repeated blood
      sampling for measurement of vasopressin and oxytocin concentrations in plasma.
      Recording of effects of vasopressin and oxytocin on isolated myometrium.
      Estimation of myometrial concentrations of vasopressin V1a and oxytocin
      receptors. Measurement of plasma oestradiol and progesterone. MAIN OUTCOME
      MEASURES: Vasopressin- and oxytocin-induced increases of the area under the in
      vivo recording curve over 10 minutes and EC50 concentrations of dose-responses in
      vitro. Concentrations of vasopressin V1a and oxytocin receptors. RESULTS:
      Vasopressin was on average four times more potent than oxytocin in vivo. The
      effect of vasopressin premenstrually was more pronounced than in women under
      oestrogen influence only (proliferative phase-hyperproliferation; P = 0.02), and
      tended to be more marked than in those in the luteal phase (P = 0.07). No
      significant variation in oxytocin response with the hormonal state was observed.
      EC50 concentrations of vasopressin were more than 20 times lower than those of
      oxytocin. The median concentration of the vasopressin V1a receptor was 208 (range
      139-343) fmol/mg protein and that of the oxytocin receptor 49 (38-87) fmol/mg
      protein. Vasopressin receptor concentrations and in vivo effects of this peptide
      did not correlate, whereas for those of oxytocin a significant correlation was
      observed (P = 0.02). CONCLUSION: The high potency of vasopressin in nonpregnant
      women, particularly premenstrually, firmly supports an aetiological importance of
      this peptide in the uterine hyperactivity of primary dysmenorrhoea. Oxytocin
      seems to be less important in this condition in view of its much smaller potency
      and the absence of increase in effect premenstrually. Vasopressin appears to
      influence both the oxytocin and the vasopressin V1a receptor sites in the uterus,
      whereas oxytocin acts specifically on its own receptor.

PMID- 8534629
TI  - Reduction of menstrual blood loss in women suffering from idiopathic menorrhagia
      with a novel antifibrinolytic drug (Kabi 2161).
AB  - OBJECTIVE: To compare the effect of Kabi 2161 (a prodrug of tranexamic acid) and
      placebo on the reduction of menstrual blood loss in women suffering from
      idiopathic menorrhagia and to evaluate tolerance and effectiveness in a two-dose
      regimen. DESIGN: A randomised, double blind parallel group study using double
      dummy technique. SETTING: The departments of gynaecology at three medical centres
      in Sweden. SUBJECTS: Ninety-one outpatients visiting the gynaecological clinics
      from March 1991 to May 1992 were randomised into the study; 68 women fulfilled
      the study. INTERVENTIONS: Two run-in cycles, followed by administrations of Kabi
      2161 (600 mg) tablets (1 four times daily or 2 twice daily) or placebo for the
      first five days of three menstrual cycles. MAIN OUTCOME MEASURES: Objective
      measurement of the change in menstrual blood loss during the treatment periods
      compared with menstrual blood loss during the run-in periods. RESULTS: A
      statistically significant reduction of menstrual blood loss was found for each
      treatment group, compared with the placebo group (P < 0.001). The mean reduction
      with 95% confidence interval (CI) was 33% (24-40) in the group treated with 1
      four times daily and 41% (33-49) in the group treated 2 twice daily. The
      difference between the treated groups in reduction of menstrual blood loss is not
      significant. No significant differences were found in the frequencies of reported
      unwanted events during run-in and during treatment between the different
      treatment groups. There were also no significant differences between the
      treatment groups and the placebo group. CONCLUSION: Kabi 2161 in a dosage of 2.4
      g per day gave a statistically significant reduction in objectively measured
      menstrual blood loss in a two (41%) as well as in a four (33%) dosage regimen
      compared with placebo. Frequency of unwanted events did not differ from those
      during run-in or from those in the placebo group. The optimal daily dosage needs
      to be further evaluated in a dose titration study.

PMID- 8534631
TI  - A modification of the Cherney incision in gynaecological oncology surgery.

PMID- 8534630
TI  - The effect of social deprivation on birthweight, excluding physiological and
      pathological effects.
AB  - OBJECTIVE: To study the effect of social deprivation on birthweight, excluding
      the effect of known physiological factors and exploring the effect of possible
      pathological factors. DESIGN: Retrospective analysis of computerised obstetric
      database. SETTING: Two teaching hospitals and an associated district general
      hospital which provided a defined catchment area in the East Midlands. SUBJECTS:
      The final analysis included 7493 women with complete datasets and gestations of
      between 259 and 300 days at delivery, dated by ultrasound scan. MAIN OUTCOME
      MEASURES: Smoking habit, alcohol consumption, weight gain during pregnancy,
      systolic and diastolic blood pressures at booking, bleeding during pregnancy and
      Jarman score; also, the effect of these variables on birthweight, adjusted for
      the effects of physiological factors using the individualised birthweight ratio.
      RESULTS: Smoking during pregnancy reduced birthweight but the effect is not
      linear, becoming less marked as the number of cigarettes smoked increases.
      Alcohol intake, diastolic and systolic blood pressures at the booking visit and
      vaginal bleeding during early pregnancy were not significantly related to
      birthweight. Pregnancy weight gain was significantly positively related to
      birthweight especially in the normal weight range (60-99 kg). A multivariate
      analysis including physiological and pathological factors found increasing Jarman
      score to be negatively related to birthweight. CONCLUSIONS: In this central
      British population social deprivation is correlated negatively with birthweight:
      the most socially deprived mothers have the smallest babies. This association
      cannot be explained in terms of physiological differences in the population nor
      in a higher prevalence of known pathological factors.

PMID- 8534632
TI  - Serum levels of insulin-like growth factor-1 in first trimester of diabetic
      pregnancy: relation to early growth delay.

PMID- 8534633
TI  - Intravesical instillation of oxybutynin in women with idiopathic detrusor
      instability: a randomised trial.

PMID- 8534634
TI  - Glucose homeostasis in adulthood and in pregnancy in a patient with hepatic
      glycogen synthetase deficiency.

PMID- 8534635
TI  - Vaginal trauma occurring while sliding down a water chute.

PMID- 8534636
TI  - The management of severe ovarian hyperstimulation syndrome.

PMID- 8534637
TI  - Chronic pelvic pain caused by residual ovaries and other ovarian remnants.

PMID- 8534638
TI  - Does early growth delay occur in diabetic pregnancy.

PMID- 8534639
TI  - Standing at work and preterm delivery.

PMID- 8534640
TI  - Planned abdominal compared with planned vaginal birth in triplet pregnancies.

PMID- 8534641
TI  - Inferior retractor plication surgery for lower lid entropion with trichiasis in
      ocular cicatricial pemphigoid.
AB  - AIMS: To assess the outcome of inferior retractor plication surgery for lower lid
      entropion in patients with ocular cicatricial pemphigoid (OCP). This technique
      avoids surgery on the conjunctiva that can result in exacerbations of disease
      activity. METHODS: This prospective study assessed the outcomes of a standard
      'Jones' type plication in 14 lids of 10 patients with OCP. Seven patients were
      taking systemic immunosuppression and no patients had conjunctival inflammation
      for the 4 months before surgery. RESULTS: Life table analysis showed a 77% chance
      of anatomical success at 2 years and a 54% chance of completely preventing lash
      globe touch. The surgery did not cause clinical activation of conjunctival
      inflammation or other complications. Anatomical failure was primary (n = 2) and
      due to late cicatrisation (n = 1). Three further cases had restoration of normal
      anatomy but the patients had persistently misdirected lashes that touched the
      globe. CONCLUSION: This technique gives good anatomical success over long periods
      and is particularly safe when there is no conjunctival inflammation present
      before surgery.

PMID- 8534642
TI  - Dawbeney Turberville--a seventeenth century ophthalmologist.

PMID- 8534643
TI  - Sodium hyaluronate eyedrops in the treatment of dry eyes.
AB  - BACKGROUND: Several studies in the past have attempted to demonstrate the
      efficacy of sodium hyaluronate in the treatment of dry eyes. However, results
      have been conflicting and a definite conclusion has not yet been reached. This
      study recruited a larger group of patients and has incorporated for the first
      time both fluorescein and rose bengal staining in the evaluation of the
      epithelium. METHODS: Eighteen albino rabbit corneas were used in a basic animal
      study to demonstrate the efficacy of sodium hyaluronate by comparing the effects
      on the rate of epithelial healing. The optimal concentration to be used in the
      clinical trial was determined from the results of the basic study. In the
      clinical study 104 patients with dry eye syndrome were enrolled in a double
      masked controlled clinical trial. Patients received sodium hyaluronate drops in
      one eye and control medication in the other eye for 4 weeks. Grading of
      subjective symptoms and clinical examinations were performed at 2 and 4 weeks.
      RESULTS: In the animal study sodium hyaluronate at concentrations of 0.1% and
      0.5% significantly accelerated the recovery time of iodine vapour induced corneal
      erosions (p < 0.01). In the clinical study no statistical significance was
      observed in the improvement of subjective symptoms or rose bengal staining, while
      fluorescein scores significantly improved in eyes receiving sodium hyaluronate (p
      = 0.0001) at 4 weeks. CONCLUSION: Sodium hyaluronate drops applied in six daily
      doses could not be demonstrated to offer advantages over conventional tear
      supplies in the improvement of subjective symptoms, but may play a role in
      maintaining a healthy corneal epithelium.

PMID- 8534644
TI  - Diode laser photocoagulation to the vascular retina for progressively advancing
      retinopathy of prematurity.
AB  - AIMS: To estimate the effectiveness of diode laser photocoagulation of the retina
      posterior to the ridge in eyes with retinopathy of prematurity (ROP). METHODS:
      Diode laser photocoagulation was applied posterior to the fibrovascular ridge in
      stage 4a ROP in six eyes of four infants and in advancing stage 3+ in two eyes of
      one infant. Seven eyes had previously been unsuccessfully treated with diode
      laser photocoagulation anterior to the ridge. RESULTS: Six eyes of four children
      had total regression, two eyes of two children had flat maculae with residual
      peripheral tractional detachment and maintained vision. CONCLUSION: These
      preliminary results indicate that diode laser photocoagulation posterior to the
      ridge may be a useful treatment in late stage 3 and stage 4A ROP following failed
      laser treatment to the avascular retina in threshold stage 3 disease.

PMID- 8534645
TI  - Warming lignocaine reduces the pain of injection during peribulbar local
      anaesthesia for cataract surgery.
AB  - AIMS: To test if the simple technique of warming lignocaine reduces the pain of
      injection during local anaesthetic cataract surgery. METHODS: Sixty patients
      undergoing peribulbar local anaesthesia for cataract surgery were allocated
      randomly to receive either warm (37 degrees C) or cold (room temperature) plain
      2% lignocaine for the injection. Pain was assessed subjectively by asking the
      patients to score their pain from 0 (no pain) to 10 (most severe pain
      imaginable). RESULTS: The mean pain score for the warm group was 2.3 (SD 1.3) in
      comparison with a mean score of 5.5 (1.0) for the cold group (p < 0.01).
      CONCLUSIONS: The process of warming lignocaine to 37 degrees C has been found to
      reduce significantly the pain of injection during peribulbar local anaesthesia.
      It is recommended that this technique be more widely adopted in order to minimise
      patient's discomfort.

PMID- 8534646
TI  - HTLV-I associated uveitis in central Japan.
AB  - AIMS/BACKGROUND: Recently HTLV-I has been shown to cause a kind of endogenous
      uveitis in south west Japan, where HTLV-I infection is highly endemic. To
      investigate further the association of HTLV-I infection with the incidence of
      this uveitis, HTLV-I seroprevalence in central Japan, where HTLV-I infection is
      not endemic, was studied. METHODS: HTLV-I seroprevalence was investigated in 1579
      patients with various ocular diseases and 1251 normal volunteers as a younger
      control group. Then HTLV-I seroprevalence was compared in each group. RESULTS: Of
      1579 patients with various ocular diseases, 38 (2.41%) were seropositive. There
      was a statistically significant difference in HTLV-I seroprevalence between the
      undefined uveitis group and non-uveitic ocular diseases group (p < 0.05, Yates's
      correction). However, the seroprevalence in younger patients with undefined
      uveitis did not differ significantly from that in other groups. As regards the
      incidence of this type of uveitis, six of 12 (50%) seropositive patients, who
      were born in south west Japan and had lived in this area for 35 years, developed
      this undefined uveitis whereas only two of 26 (7.69%) seropositive patients in
      the other areas in Japan developed this uveitis. The difference was statistically
      significant (p < 0.05, Fisher's exact probability test). CONCLUSION: These
      results suggest that the incidence of this type of endogenous uveitis could be
      greatly influenced by environmental or hereditary factors including HLA.

PMID- 8534647
TI  - Fuchs' heterochromic uveitis and sarcoidosis.
AB  - AIMS/BACKGROUND: The aetiology of Fuchs' heterochromic uveitis (FHU) is unknown
      although it can occur in combination with a number of different ocular
      conditions. Five patients with FHU who show an association with sarcoidosis were
      studied. METHODS: Four patients with clinical signs compatible with FHU who had
      elevated serum angiotensin converting enzyme levels (sACE), and a fifth case with
      a normal sACE and a positive Kveim test were described. RESULTS: All five cases
      had iris nodules, two later developed mutton fat keratic precipitates, and one
      had peripheral retinal periphlebitis. Of the four cases with elevated sACE, one
      had respiratory function test abnormalities and an abnormal chest x ray
      compatible with pulmonary sarcoidosis. Another had a chorioretinal scar and
      developed intermediate uveitis 2 years after presentation. CONCLUSIONS: In all of
      these cases a diagnosis of FHU may represent a specific secondary ocular response
      to sarcoidosis rather than a primary idiopathic uveitis syndrome. Although FHU
      remains a clinical diagnosis, routine uveitis investigations should still be
      performed in this group of patients.

PMID- 8534648
TI  - Causes of suppurative keratitis in Ghana.
AB  - AIMS: Suppurative keratitis is a serious problem in all tropical countries, but
      very little information is available about the causative organisms in Africa. The
      objectives were to identify the causative organisms and the proportion of cases
      caused by fungi in southern Ghana, and to determine whether correct decisions
      about treatment could be made on the basis of Gram stain in the eye clinic.
      METHODS: Scrapings were taken from corneal ulcers of consecutive new patients
      presenting at Korle Bu Hospital, Accra, and inoculated on 'chocolate' and
      Sabouraud's agars. Further scrapings were taken for Gram staining and
      interpretation in the eye clinic. Duplicate slides were assessed by an
      experienced microbiologist in the UK. RESULTS: One or more organisms were
      cultured from 114 of 199 patients (57.3%), the most common being Fusarium
      species, Pseudomonas aeruginosa, and Staphylococcus epidermidis. Fungi, alone or
      in combination, were isolated from 56% of the patients who had positive cultures.
      In total, 122 patients (61.3%) had their treatment either determined or altered
      based on the results of the microbiological diagnosis; in 87 of these solely on
      the basis of direct microscopic examination. CONCLUSIONS: Infection by
      filamentous fungi accounted for more than half of the ulcers from which cultures
      were obtained. Both training in technique and experience in interpretation are
      necessary for microscopy based diagnosis by staff in the clinic to be of greatest
      value. Direct microscopy was particularly useful for detecting fungi.

PMID- 8534649
TI  - The South Asian Cataract Management Study. I. The first 662 cataract surgeries: a
      preliminary report.
AB  - AIMS: The first 662 cases of a multicentre randomised clinical trial of
      intracapsular cataract extraction (ICCE) with and without implantation of a four
      point multiflex (Cilco Kelman Choyce Modification) anterior chamber intraocular
      lens (AC IOL) were studied after 6 weeks to compare frequency of surgical
      complications, short term clinical outcomes, and corneal endothelial cell loss
      between groups. METHODS: Randomisation was performed after screening for
      predetermined inclusion and exclusion criteria. Demographics, visual acuities,
      intraocular pressures, and corneal endothelium cell data were recorded
      preoperatively and at 6 weeks. Details of surgical procedure, complications, and
      postoperative adverse reactions were recorded. Monitoring of the study was
      secured by a standardised image documentation procedure on all patients using the
      IMAGEnet digital imaging system. Analysis of corneal endothelial cell images was
      done using the CELL SOFT software analysis program. RESULTS: 343 patients were
      randomised to IOL and 319 to no IOL. Twelve IOL implantations (3.5%) were aborted
      because of complications. A complication was reported in 103 (15.6%) of the
      surgical procedures (IOL = 16.9%, no IOL = 14.1%, p = 0.37). The most frequent
      complication observed was vitreous loss followed by plain capsular rupture,
      unplanned ECCE, and iris dialysis. Mean corneal endothelial cell loss 6 weeks
      after surgery was 17.2% (SD 13.1%) in the total study population (IOL = 18.5% no
      IOL = 16.1%, p = 0.05). The postoperative complications registered until 6 week
      follow up were significantly higher in the IOL group (IOL = 6.9%, no IOL = 2.6%,
      p = 0.02), mainly due to mild to moderate iritis needing prolonged use of
      steroids. Eighty nine per cent of the patients had a best corrected visual acuity
      of 6/18 or better. There was no significant difference in visual outcome between
      study groups. CONCLUSIONS: The implantation of a multiflex AC IOL in primary ICCE
      surgery in the centres of this study did not increase the risk of surgical
      complications or short term sight threatening adverse clinical outcomes compared
      with ICCE without lens. Comparisons of corneal endothelial cell loss after 6
      weeks between study groups showed no clinically significant difference. The
      difference in mean cell loss between groups was statistically significant.

PMID- 8534650
TI  - Some blood plasma constituents correlate with human cataract.
AB  - AIMS: To look for differences between matched pairs of patients and controls in
      concentrations of various plasma constituents which might indicate dysfunctions
      associated with cataract. METHOD: One thousand patients were taken from the
      cataract waiting list of a specialist eye hospital. For each patient a matched
      control of the same sex and half-decade of age but without cataract was taken
      from the patient list of the family doctor of the patient; the control was the
      next alphabetically after the patient on the doctor's list. The patients and
      controls were visited in their homes by a team of nurses who performed
      venepunctures and collected information for a questionnaire. Eye examinations
      were performed by a team of ophthalmologists. RESULTS: Significant differences
      were found between the cataract and control groups in 10 of the 18 examined
      plasma constituents. A constellation of three--bilirubin, alkaline phosphatase,
      and gamma glutamyl transpeptidase--was significantly higher in the cataract
      group, suggesting subclinical liver dysfunction as a risk factor. Steroid
      treatment and diabetes increased cataract risk. Endogenous basal plasma cortisol
      levels were raised in the cataract group, irrespective of steroid use and
      diabetic status. Alkaline phosphatase, calcium, glucose, and sodium were all
      raised in the cataract group. Given the raised total protein and albumin also
      found in the cataract group, the lower albumin/(total protein-albumin) ratio (an
      approximation for albumin/globulin ratio) may imply an increase in globulin,
      suggestive of possible (chronic) infection. Total cholesterol was lower in the
      cataract group. CONCLUSION: Human cataract in older age groups seems to be due to
      an accumulation of risk factors, even if individual mean concentrations are well
      within normal limits but, of course, differing significantly from the
      corresponding means in the control population.

PMID- 8534651
TI  - Correlation of tear clearance rate and fluorophotometric assessment of tear
      turnover.
AB  - BACKGROUND: The study sought to determine dynamic changes and theoretical bases
      of a clinical diagnostic test, the tear clearance rate. METHODS: Thirty four
      healthy subjects ranging in age from 22 to 84 years underwent examination of tear
      clearance rate, the Schirmer test with anaesthesia, as well as fluorophotometric
      measurement of tear turnover, tear volume, and tear flow. By applying 0.5%
      fluorescein into the conjunctival sac and subsequently measuring colour fades on
      a Schirmer strip, the tear clearance rate for assessing tear drainage was divided
      into nine grades. The results of the tear clearance rate were compared with those
      of the basal tear turnover and tear flow obtained from fluorophotometry. RESULTS:
      Significant relations were found between the tear clearance rate and the basal
      tear turnover or tear flow (r = 0.91 and 0.79, respectively, p = 0.0001).
      Considering the grades of progression from low to high, each grade of tear
      clearance rate showed a 12.5% increase in basal tear turnover (3.59%/min) and
      tear flow (0.38 microliter/min). There was no significant correlation between age
      and the basal tear turnover, tear volume, tear flow, or the tear clearance rate.
      CONCLUSION: The tear clearance rate is proposed as a simple and useful way to
      estimate basal tear turnover and tear flow, and measure tear drainage indirectly.

PMID- 8534652
TI  - Role of glucose regulatory mechanisms in diabetic retinopathy.

PMID- 8534653
TI  - Resolution of calcific band keratopathy after lowering elevated serum calcium in
      a patient with sarcoidosis.

PMID- 8534654
TI  - Pseudoexfoliation material on an acrylic lens.

PMID- 8534655
TI  - Giant dacryops in a patient with ocular cicatricial pemphigoid.

PMID- 8534656
TI  - Angiolymphoid hyperplasia with eosinophilia (Kimura's disease) of the
      conjunctiva.

PMID- 8534657
TI  - Monoclonal antibody therapy of chronic intraocular inflammation using Campath-1H.

PMID- 8534658
TI  - Bilateral hyphaema following diode laser for retinopathy of prematurity.

PMID- 8534659
TI  - Corneal transplantation and infectious hepatitis.

PMID- 8534660
TI  - Orbital lymphoma in systemic sarcoidosis.

PMID- 8534661
TI  - Reducing bias during intraocular pressure measurement.

PMID- 8534662
TI  - The end stage of birdshot retinochoroidopathy.

PMID- 8534664
TI  - Stem cells of the ocular surface: scientific principles and clinical
      applications.

PMID- 8534663
TI  - High frequency ultrasound.

PMID- 8534665
TI  - Towards cytokine insight in sight.

PMID- 8534666
TI  - High frequency ultrasound imaging in pupillary block glaucoma.
AB  - BACKGROUND: The diagnosis of pupillary block glaucoma requires sufficient clarity
      of the ocular media. This is particularly important for assessment of both the
      presence and patency of an iridotomy, and the determination of central anterior
      chamber depth. METHODS: High frequency ultrasonography was used in three patients
      with suspected pupillary block to determine iris configuration, posterior chamber
      volume, and ciliary body conformation. RESULTS: All patients demonstrated high
      frequency ultrasonographic findings consistent with pupillary block: iris bombe,
      a formed posterior chamber, and a lack of anterior rotation of the ciliary
      processes. CONCLUSION: High frequency ultrasound imaging appears to be a valuable
      adjunct in making or corroborating the diagnosis of pupillary block glaucoma.

PMID- 8534667
TI  - Surgical management of ocular surface disorders using conjunctival and stem cell
      allografts.
AB  - AIMS: The aim of this work was to investigate different surgical options for the
      repair of the ocular surface, using various extensions of the procedure of limbal
      stem cell allotransplantation. METHODS/RESULTS: Straightforward lamellar limbal
      transplantation was performed in one patient with contact lens induced limbal
      stem cell failure. A second patient with a neoplastic corneal lesion underwent
      limbal allotransplantation, followed later by a second procedure in which 360
      degrees of limbus and the entire ocular surface was transplanted. A third patient
      who had suffered extensive chemical burns was treated by penetrating keratoplasty
      to restore central corneal clarity, followed later by a lamellar allograft
      comprising a 360 degrees annulus of peripheral cornea to repair the ocular
      surface. A fourth patient with long standing, chronic trachomatous eye disease
      underwent allotransplantation of the upper lid tarsal plate and conjunctiva, with
      reconstruction of the fornix. Finally, a child with Goldenhar's syndrome
      underwent reconstruction of the medial fornix with autologous buccal mucosa,
      followed by a lamellar corneal and conjunctival allograft. A stable ocular
      surface has been achieved in each case and there have been no obvious rejection
      episodes. CONCLUSION: Limbal allotransplantation can be extended to engraftment
      of the entire superficial cornea, limbus, conjunctiva, and tarsal plate in
      patients with a range of pathologies. We have described the surgical management
      of five cases which demonstrate the potential of the technique, but which raise
      questions which still need to be explored.

PMID- 8534668
TI  - Reproducibility of corneal astigmatism measurements with a hand held keratometer
      in preschool children.
AB  - AIMS: To evaluate the overall accuracy and reproducibility of the Alcon portable
      autokeratometer (PAK) measurements in infants and young children. METHODS: The
      accuracy of the Alcon PAK in measuring toric reference surfaces (1, 3, 5, and 7
      D) under various suboptimal measurement conditions was assessed, and the
      reproducibility of PAK measurements of corneal astigmatism in newborn infants (n
      = 5), children (n = 19, age 3-5 years), and adults (n = 14) was evaluated.
      RESULTS: Measurements of toric reference surfaces indicated (a) no significant
      effect of distance (17-30 mm) on accuracy of measurements, (b) no systematic
      relation between amount of toricity and accuracy of measurements, (c) no
      systematic relation between angle of measurement and accuracy, (d) no difference
      in accuracy of measurements when the PAK is hand held in comparison with when it
      is mounted, (e) no difference in accuracy of measurements when axis of toricity
      is oriented obliquely than when it is oriented horizontally, with respect to the
      PAK, and (f) a small positive bias (+0.16 D) in measurement of spherical
      equivalent. The PAK did not prove useful for screening newborns. However,
      measurements were successfully obtained from 18/19 children and 14/14 adults.
      There was no significant difference in median measurement deviation (deviation of
      a subject's five measurements from his/her mean) between children (0.21 D) and
      adults (0.13 D). CONCLUSIONS: The PAK produces accurate measurements of surface
      curvature under a variety of suboptimal conditions. Variability of PAK
      measurements in preschool children is small enough to suggest that it would be
      useful for screening for corneal astigmatism in young children.

PMID- 8534669
TI  - Effect of squint surgery on pupillary diameter.
AB  - AIM: To investigate the effect that squint surgery has on pupillary diameter.
      METHODS: The effect of squint surgery on pupil size was investigated in 19
      patients. RESULTS: A significant mydriasis in the operated eye was observed when
      compared with the unoperated eye. This was independent of the number or type of
      extraocular muscles operated upon. CONCLUSION: It is hypothesised that this
      change in pupillary diameter results from the release of neurotransmitters from
      tissues damaged during surgery.

PMID- 8534670
TI  - Corneal sensitivity in patients with leprosy and in controls.
AB  - AIMS: In a quantitative prospective study the corneal sensation in patients with
      leprosy was compared with age matched controls. METHODS: The patients with
      leprosy were classified as paucibacillary and multibacillary and were divided in
      three groups: (1) patients without clinically detectable eye pathology; (2)
      patients with lagophthalmos, (3) patients with signs of iridocyclitis. The
      corneal sensitivity was assessed with the Cochet and Bonnet aesthesiometer.
      RESULTS: There was a significant decrease in corneal sensitivity in
      multibacillary patients without clinically detectable eye pathology and in
      patients with lagophthalmos or iritis when compared with controls. A significant
      correlation between the loss of power of the orbicularis oculi muscle and the
      degree of corneal sensation loss could not be established. No significant
      decrease in corneal sensitivity was found in paucibacillary patients without eye
      pathology compared with the control group. CONCLUSION: The results of this study
      showed that loss of corneal sensation can occur while there is no clinically
      detectable eye pathology, at least in multibacillary patients. Regular checkups
      of the corneal sensation should, therefore, be part of the routine control of
      leprosy patients. Health education on eye care and early warning signs should be
      encouraged.

PMID- 8534671
TI  - Absence of effect of simvastatin on the progression of lens opacities in a
      randomised placebo controlled study. Oxford Cholesterol Study Group.
AB  - AIMS: A detailed assessment of ophthalmic effects of an HMG CoA reductase
      inhibitor, simvastatin, was performed. METHODS: Six hundred and twenty one
      individuals considered to be at increased risk of coronary heart disease were
      randomised, following an 8 week placebo 'run in' period, to receive 40 mg daily
      simvastatin, 20 mg daily simvastatin, or matching placebo. Patients with a
      baseline corrected visual acuity better than 6/24 and without a history of
      cataract were eligible for detailed ophthalmic assessment at 6 months (539
      patients assessed) and at 18 months (474 patients assessed). RESULTS: No
      significant differences between the treatment groups were detected at the 6 month
      or 18 month visit in the refractive condition of the eye or in the mean
      intraocular pressure. Nor were there clear differences in the Oxford grading
      system scores for various measures of the major types of cataract (cortical
      spokes, posterior subcapsular cataract, nuclear brunescence, white scatter) or
      for other morphological features visible within the lens (fibre folds or focal
      dots). Scheimpflug slit image photographs and retroillumination analysis of the
      percentage of cataract within a defined region of the lens were also performed at
      each visit, with no clear differences observed between the treatment groups.
      CONCLUSION: This single centre double blind study found no good evidence of any
      adverse effects of 18 months of simvastatin treatment on lens opacity formation,
      using a variety of validated techniques to assess cataract development. Routine
      clinic follow up of visual symptoms and admission to hospital for ophthalmic
      procedures over 5 years of treatment was also reassuring, with no excess adverse
      outcomes observed with simvastatin.

PMID- 8534672
TI  - Energetics of the quinone electron acceptor complex in Rubrivivax gelatinosus.
AB  - The pH and temperature dependences of the free energy stabilization of the Q-A
      and Q-B semiquinone anions (QA and QB are respectively the primary and secondary
      quinone electron acceptors) were studied in antenna-reaction centre complex from
      Rubrivivax (R.) gelatinosus. This was achieved by measuring the rate constants of
      the P+Q-A (kAP) and P+Q-B (kBP) (P is the primary electron donor) charge
      recombination processes by flash-induced absorption spectroscopy. Despite the
      high primary sequence analogies of the QA and QB protein pockets between R.
      gelatinosus and the much more studied species as Rps. viridis, Rb. sphaeroides
      and Rb. capsulatus, the energetic behaviour of the quinone complex of R.
      gelatinosus appears to be somewhat different: (i) above pH 10, kAP decreases,
      whereas it increases in Rps. viridis; this suggests the presence of a
      protonatable group that stabilizes I- (I is a bacteriopheophytin electron
      acceptor) rather than Q-A; (ii) the pH dependence of kBP is unusually flat in the
      range 4-7.5, possibly reflecting that a substantial part of the P+Q-B charge
      recombination proceeds via the direct route through the protein by an electron
      tunnelling mechanism, at variance to what is observed in the three species
      mentioned above; (iii) the very substantial increase of kBP observed above pH 7.5
      is reasonably well described by the presence of two apparent protonatable groups:
      pK1QB = 9.4, pK1Q-B = 11 and pK2QB = 8.5, pK2Q-B = 9.4. The latter group was not
      reported in Rps. viridis, Rb. sphaeroides or Rb. capsulatus. We conclude that the
      apparent pK values measured here in R. gelatinosus may reflect the contribution
      as a whole of several and/or distant groups rather than of well-defined residues.

PMID- 8534673
TI  - Isolation and characterization of a Photosystem II complex from the red alga
      Cyanidium caldarium: association of cytochrome c-550 and a 12 kDa protein with
      the complex.
AB  - A Photosystem II (PS II) complex was purified from an acidophilic as well as a
      thermophilic red alga, Cyanidium caldarium. The purified PS II complex was
      essentially devoid of phycobiliproteins and other contaminating components, and
      showed a high oxygen-evolving activity of 2375 mumol O2/mg Chl per h using phenyl
      p-benzoquinone as the electron acceptor. The expression of this high activity did
      not require addition of exogenous Ca2+, although EDTA reduced the activity by
      40%. This effect of EDTA can be reversed not only by Ca2+ but also by Mg2+; a
      similar Mg2+ effect has been observed in purified cyanobacterial PS II but not in
      higher plant PS II. Immunoblotting analysis indicated the presence of major
      intrinsic polypeptides commonly found in PS II from cyanobacteria and higher
      plants as well as the extrinsic 33 kDa protein. Antibodies against the extrinsic
      23 and 17 kDa proteins of higher plant PS II, however, did not crossreact with
      any polypeptides in the purified PS II, indicating the absence of these proteins
      in the red alga. In contrast, two other extrinsic proteins of 17 and 12 kDa were
      present in the red algal PS II; they were released by 1 M Tris or Urea/NaCl
      treatment but not by 1 M NaCl. The 17 kDa polypeptide was identified to be
      cytochrome c-550 from heme-staining, immunoblot analysis and N-terminal amino
      acid sequencing, and the 12 kDa protein was found to be homologous to the 12 kDa
      extrinsic protein of cyanobacterial PS II from its N-terminal sequence. These
      results indicate that PS II from the red alga is closely related to PS II from
      cyanobacteria rather than to that from higher plants, and that the replacement of
      PS II extrinsic cytochrome c-550 and the 12 kDa protein by the extrinsic 23 and
      17 kDa proteins occurred during evolution from red algae to green algae and
      higher plants.

PMID- 8534674
TI  - Modulation of the Ca2+,Mg(2+)-ATPase of sarcoplasmic reticulum by the
      hypothalamic hypophyseal inhibitory factor.
AB  - We have studied the effect of the endogenous inhibitor of the Na+ and Ca2+ pumps,
      HHIF, on sarcoplasmic reticulum (SR) vesicles. The effect of HHIF on the SR
      Ca2+,Mg(2+)-ATPase activity shows a biphasic pattern. Low HHIF concentrations
      activate the Ca2+,Mg(2+)-ATPase by dissipation of Ca2+ gradient across the SR
      membrane. Higher concentrations irreversibly inhibit this activity following a
      slow kinetic process both in intact SR membranes and in purified Ca2+,Mg(2+)
      ATPase. Differential scanning calorimetry shows that the Ca2+,Mg(2+)-ATPase is
      denatured after incubation with HHIF concentrations which produced full
      inhibition of its activity. Micromolar Ca2+ and millimolar Mg2+ ADP protect
      against the irreversible inhibition of the Ca2+,Mg(2+)-ATPase by HHIF. The
      concentration of HHIF which produces 50% inhibition depends upon SR membrane
      concentration and upon the lipid:protein ratio in purified Ca2+,Mg(2+)-ATPase.
      From this we have obtained a partition coefficient for binding of HHIF to SR
      membranes of 0.6 (microgram SR protein/ml)-1.

PMID- 8534675
TI  - Aerobic and anaerobic functioning of superoxide-producing cytochrome b-559
      reconstituted with phospholipids.
AB  - Cytochrome b-559 reconstituted with phospholipids and FAD represents the simplest
      model of the respiratory burst NADPH oxidase and reproduces the main catalytic
      features of this system (Koshkin, V. and Pick, E. (1993) FEBS Lett. 327, 57-62;
      (1994) FEBS Lett. 338, 285-289). In the present report it is shown that
      activation by oxygen, characteristic of the NADPH oxidase complex, is an
      intrinsic property of flavocytochrome b-559, in principle independent of its
      complexation with the other components of NADPH oxidase. Facilitation of electron
      transfer from NADPH to FAD is found to be the reason for this phenomenon. Kinetic
      studies of anaerobic operation of flavocytochrome b-559 revealed the functional
      heterogeneity of two hemes, manifested as a dramatic difference in their
      reducibility under these conditions.

PMID- 8534676
TI  - Enzymes and associated electron transport systems that catalyse the respiratory
      reduction of nitrogen oxides and oxyanions.

PMID- 8534677
TI  - Selected papers from the 15th Annual Conference on Peritoneal Dialysis.
      Baltimore, Maryland, February 1995.

PMID- 8534678
TI  - Modification of creatinine clearance by estimation of residual urinary creatinine
      and urea clearance in CAPD patients.
AB  - The use of creatinine clearance for adequacy of continuous ambulatory peritoneal
      dialysis (CAPD) requires consideration of the fact that a significant fraction of
      residual renal creatinine clearance is contributed by tubular secretion. We
      analyzed 123 peritoneal dialysis (PD) patients and corrected the residual renal
      creatinine clearance by averaging renal creatinine and urea clearance to estimate
      the glomerular filtration rate (GFR). Modified total creatinine clearance
      (peritoneal plus estimated renal GFR) was compared with total creatinine
      clearance (peritoneal plus total renal creatinine clearance). Modified and total
      creatinine clearances were not significantly different in patients with a total
      creatinine clearance less than 60 L/week/1.73 m2 body surface area (BSA), but a
      significantly lower modified total creatinine clearance was seen with patients
      having greater than 60 L/week/1.73 m2 BSA of total creatinine clearance. The
      correlation was better between KT/V and modified total creatinine clearance (r =
      0.74) as compared to KT/V and total creatinine clearance (r = 0.67). We suggest
      that if creatinine clearance is used for peritoneal dialysis (PD) adequacy, the
      contribution of residual renal function should be calculated as the average of
      renal creatinine and urea clearance, thus estimating creatinine clearance only by
      the GFR. Further long-term studies are needed to confirm that modification of
      total creatinine clearance will better predict clinical outcome.

PMID- 8534679
TI  - Residual renal function and nutritional parameters in CAPD.
AB  - In continuous ambulatory peritoneal dialysis (CAPD) residual renal function (RRF)
      plays an important role in the total amount of weekly clearances of small
      molecules. The purpose of this study was to determine if there were any
      differences in certain nutritional parameters between patients with and without
      RRF, total weekly clearance (KT/V) being equal. Therefore, we compared two groups
      of patients with equal weekly KT/V: group A without RRF [n = 7, KT/V 2.07 +/-
      0.2) and group B with RRF (n = 7, KT/V 2.11 +/- 0.1, urea clearance 1.13 +/- 0.8,
      creatinine clearance 2.01 +/- 1.5 mL/min, contributing on the average of 15%
      (range 5.5%-28%) to the determination of KT/V]. The two groups were selected from
      52 patients on CAPD for more than 9 months and they were comparable in age (A =
      64.6 +/- 7 years, B = 64.1 +/- 7 years), duration of dialysis (A = 39.8 +/- 25
      months, B = 36.3 +/- 31 months), body weight (A = 64 +/- 3.9 kg, B = 64.7 +/- 7.4
      kg), and body mass index (A = 26.6 +/- 2.9, B = 25.8 +/- 3.6). The two groups
      turned out to be different in transferrin (A = 209 +/- 51, B = 278 +/- 24 mg/dL,
      p < 0.006), normalized protein catabolic rate (PCRN) (A = 0.87 +/- 0.07, B = 1.11
      +/- 0.07 g/kg/day, p = 0.00), and albumin (A = 3.31 +/- 0.1, B = 3.55 +/- 0.2, p
      < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534680
TI  - Enhanced expression of TGF-beta 1 by peritoneal macrophages in CAPD patients.
AB  - Peritoneal macrophages are the predominant cells in peritoneal dialysate. To
      clarify the role of the macrophage in fibrosis of the peritoneum in long-term
      continuous ambulatory peritoneal dialysis (CAPD) patients, we studied the
      transforming growth factor beta (TGF-beta 1) mRNA expression by peritoneal
      macrophages from peritoneal dialysis patients. Macrophages were obtained when the
      catheter was inserted and one month later. TGF-beta 1 mRNA was measured by slot
      blot hybridization using a cDNA probe. The result was that TGF-beta 1 expression
      was significantly higher in macrophages from peritoneal dialysate than that of
      macrophages obtained during catheter insertion. This suggests that peritoneal
      macrophages play a role in the pathogenesis of fibrosis of peritoneum in
      peritoneal dialysis patients. It also suggests that peritoneal macrophages in
      dialysate have been somewhat activated.

PMID- 8534681
TI  - Dialysis adequacy indices in high membrane transporters treated with short-dwell
      peritoneal dialysis.
AB  - Treatment of high-membrane transporters with continuous ambulatory peritoneal
      dialysis (CAPD) is associated with ineffective ultrafiltration, increased
      dialysate protein loss, lower serum albumin levels, and lower protein catabolic
      rates, suggesting development of inadequate dialysis. The use of short-dwell
      nightly intermittent peritoneal dialysis (NIPD) and daytime ambulatory peritoneal
      dialysis (DAPD) has not been evaluated. Patients with inadequate ultrafiltration
      secondary to rapid membrane transport [peritoneal equilibration test (PET)
      confirmation] were managed with NIPD and DAPD (group A, n = 32) and compared to
      patients on CAPD and continuous cycling peritoneal dialysis (CCPD) (group B, n =
      53) after at least 3 months of therapy. Groups A and B were similar in age,
      gender, diabetic status, prestudy months on peritoneal dialysis (PD), and
      residual renal function. No significant differences were observed between the
      groups with respect to serum albumin, daily protein loss, normalized protein
      catabolic rate (PCRN), or weekly KT/V urea indices. Diabetics demonstrated lower
      levels of serum albumin and PCRN than nondiabetics while maintaining equivalent
      KT/V urea indices. Reassessment of patients 6 months later also revealed no
      differences in outcome measures between group A (n = 20) and group B (n = 36).
      High transporters treated with NIPD and DAPD appear to have similar dialysate
      protein loss, adequacy, and nutrition indices when compared to patients on CAPD
      and CCPD. Future studies will determine if delivery of higher target small-solute
      clearances benefits patients on NIPD/DAPD as contrasted with continuous PD
      modalities (CAPD/CCPD), or diabetics compared to nondiabetics.

PMID- 8534682
TI  - Consistency of the peritoneal equilibration test in a cohort of nonselected
      Mexican CAPD patients.
AB  - The peritoneal equilibration test (PET) is a useful tool in continuous ambulatory
      peritoneal dialysis (CAPD) prescription. PET D/P ratios are reproducible in the
      same patient when performed within a short period. However, peritoneal transport
      consistency in nonselected patients over longer periods of time is debated. The
      PET was performed twice in 19 randomly selected patients (13 female) from a
      cohort of 55 patients on CAPD for 32 +/- 24 months, age 44 +/- 18 years. Mean
      time between the first and second PET was 9.6 +/- 4 months. All patients were
      peritonitis-free at least 6 weeks before each PET. Fifteen patients did not
      change transport type between the two PETs: 3 low (L), 8 low-average (LA), 3 high
      average (HA), and 1 high (H). Only 4 changed: 1 H to HA, 2 LA to HA, and 1 L to
      LA. In these 4 patients the change was centripetal (towards the mean) and less
      than 1 SD and not considered clinically significant. No differences between both
      groups in peritonitis rate, gender, age, time on dialysis, and diabetes mellitus
      status were observed. Transport type, as evaluated by the PET, was consistent
      over time in our group of patients.

PMID- 8534683
TI  - Transfer of native insulin through the peritoneal membrane during CAPD in non
      diabetic and diabetic patients.
AB  - Because of its relatively small molecular size of 5800 daltons, insulin is a
      transperitoneally diffusable substance. Insulin is also known to be a mitogenic
      coadjuvant for mice fibroblasts, and safety of its long-term intraperitoneal use
      has been questioned because of the potential risk for peritoneal fibrosis. For
      similar reasons native insulin content of the peritoneal effluent should also not
      be neglected. To our knowledge, no sufficient data are available about native
      insulin transfer to dialysate during continuous ambulatory peritoneal dialysis
      (CAPD). In this study we measured plasma and dialysate immune-reactive insulin
      levels during a 4 hour peritoneal exchange in 9 nondiabetic and 4 type II
      diabetic end-stage renal disease patients on CAPD. In both plasma and dialysate,
      insulin levels were higher in diabetic patients. At hour 4 of dwell time, plasma
      insulin was 37.5 +/- 7.9 microU/mL in non-diabetics and 64.2 +/- 34.1 microU/mL
      in type II diabetics. In both groups, dialysate insulin was 1.5 to 2 x higher
      than their simultaneous peripheral vein insulin levels and was measured as 88.1
      +/- 26.8 microU/mL in nondiabetic group and 101.7 +/- 52.6 microU/mL in the
      diabetic group at hour 4 (p < 0.005 vs 4 hour plasma level). In conclusion, in
      both diabetic and nondiabetic CAPD patients, native insulin was present in the
      dialysate in amounts exceeding simultaneous plasma levels. Equilibration with
      high portal vein insulin content through hepatic capsule may explain higher
      insulin concentrations measured in the dialysate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8534684
TI  - Sleep apnea in CAPD.
AB  - Sleep disturbances are common complaints of dialysis patients, and sleep studies
      have suggested that sleep apnea may occur frequently. We performed sleep studies
      on 18 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Our
      results indicate that 6 of 18 patients (33%) had a respiratory disturbance index
      (RDI) greater than 15, which indicates severe sleep apnea. Twelve of 18 patients
      (67%) had an RDI greater than 5, indicating clinically significant sleep apnea.
      These results suggest that sleep apnea is common in CAPD patients. The impact of
      sleep apnea on the patients' quality of life remains to be determined.

PMID- 8534686
TI  - Lipoprotein (a) levels and clinical correlations in CAPD patients.
AB  - Dyslipidemia is an important risk factor for atherosclerotic vascular disease.
      Serum lipoprotein (a) [Lp(a)] has been implicated as an independent atherogenic
      risk factor. We measured serum (Lp(a) levels in our patients and studied its
      correlations with other lipoproteins and clinical parameters. All stable patients
      on continuous ambulatory peritoneal dialysis (CAPD) for more than one month were
      enrolled in the study. Fasting serum Lp(a), total cholesterol, triglycerides, LDL
      cholesterol, HDL-cholesterol, apolipoprotein-A and apolipoprotein-B levels were
      measured on entering the CAPD program and at 3 monthly intervals. One hundred and
      nine patients (M/F: 65/44, mean age +/- SD: 59.5 +/- 12.0 years) were studied.
      Fifty-two patients had diabetes mellitus. Age- and sex-matched normals were used
      as controls. Serum Lp(a) levels were raised in 54.5% of CAPD patients compared to
      18.6% of controls (p < 0.01). There was no significant change in Lp(a) levels
      over time. Serum Lp(a) levels showed positive and negative correlations with LDL
      cholesterol and triglycerides, respectively, but not with age, sex, diabetic
      status, and serum total cholesterol and albumin levels. Thirty-six of 54 (66.7%)
      patients with serum Lp(a) levels greater than 30 mg/dL had either coronary,
      cerebral, and/or peripheral vascular disease compared to 30/55 (54.5%) of
      patients with serum Lp(a) levels less than 30 mg/dL (p = NS). In conclusion,
      serum Lp(a) levels were raised in a significant proportion of CAPD patients, but
      there was no significant association with vascular disease.

PMID- 8534685
TI  - Reduced blood levels of coagulation inhibitors in chronic hemodialysis compared
      with CAPD.
AB  - The aim of this study was to measure the coagulation inhibitors in two groups of
      uremic patients treated with hemodialysis (HD) and continuous ambulatory
      peritoneal dialysis (CAPD) to evaluate the differences in anticoagulant activity.
      In 20 patients on HD and 20 on CAPD, mean age 66 +/- 8 and 58 +/- 14 years,
      respectively, the following parameters were determined between dialysis
      exchanges: protein C (PC), protein S (PS), antithrombin III (AT III),
      electrophoresis, prothrombin activation fragment (F1+2), alpha 1 antitripsin
      (alpha 1 AT), prothrombin time (PT), and activated partial thromboplastin time
      (PTT). The mean values of PC, PS, and AT III were respectively, 95.7 +/- 16 on HD
      and 92 +/- 23 on CAPD; 82.2 +/- 13.6 on HD and 90.5 +/- 13.6 on CAPD; the mean
      value F1+2 was 1.2 +/- 0.5 on HD and 1.04 +/- 0.5 on CAPD (p < 0.05). A good
      correlation between PS and AT III% functional activity (p < 0.03, r = 0.5) in
      both groups was found. More-over, PS functional activity was inversely correlated
      with duration of dialysis (p < 0.05, r = -0.3). HD patients showed a reduction of
      coagulation inhibitors compared with CAPD patients. Such a phenomenon could
      justify the increased thrombotic risk in HD patients. Since 80% of those on HD
      and only 20% of those on CAPD received erythropoietin (EPO), the prothrombotic
      state in HD could be due to reduced PS activity secondary to EPO treatment.

PMID- 8534687
TI  - Role of automated peritoneal dialysis within a peritoneal dialysis program.
AB  - We wished to assess the impact of automated peritoneal dialysis (APD) on the
      peritoneal dialysis (PD) program. From November 1981 to December 1993, 112
      patients were started on hemodialysis (HD) as first treatment and 88 on PD
      [continuous ambulatory peritoneal dialysis (CAPD): 78, APD: 10]; respective
      average ages were 61 +/- 14 and 62 +/- 13 years. To December 1985, APD was used
      as first treatment of PD in 1/29 patients (3.4%), while subsequently, on the
      basis of a clinical and social-aptitude assessment protocol, it was used in 9/59
      patients (15.2%) with PD indication and CAPD contraindications (work: 2 patients,
      partner required: 7 patients). Of the patients who interrupted CAPD, APD was used
      in 9/21 patients (reason: social aptitude, 28.6%; clinical, 71.4%). Technique
      survival after 5 years proved no different in HD versus PD (87% vs 82%, p = NS),
      whereas in HD versus CAPD it was different (87% vs 62%, p < 0.025). The incidence
      of peritonitis in APD and CAPD with the Y-set was comparable (1/37 vs 1/40
      episode/patient-months), while germ distribution was different (p < 0.001) with
      Staphylococcus epidermidis prevailing in APD (59%). Based on our experience, APD
      may extend method acceptance criteria and reduce the technique dropout rate in
      PD; however, connection technique may need to be improved in order to reduce the
      risk of peritonitis from exogenous contamination.

PMID- 8534688
TI  - Influence of peritoneal dialysis on the progression of chronic renal failure.
AB  - To determine whether an early start of peritoneal dialysis is beneficial to the
      preservation of residual renal function, we studied the effect of peritoneal
      dialysis on the progression of glomerular sclerosis in subtotal nephrectomy rats.
      Four weeks after subtotal nephrectomy, Wistar rats were treated with peritoneal
      dialysis (PD) (through a silicone catheter, two exchanges per day with 20 mL 1.5%
      dextrose solution per exchange for 8 weeks, n = 10). Then the kidneys were
      checked. The sclerosis index was significantly lower in the PD group than that of
      the control group, which was 1.12 +/- 0.13, 1.64 +/- 0.19, respectively (p <
      0.05). This suggests that peritoneal dialysis may suppress the progression of
      chronic renal failure. An early start of PD may benefit the preservation of renal
      function in uremic patients.

PMID- 8534689
TI  - Peritoneal transport evaluation in peritonitis: comparison between methods.
AB  - Peritoneal dialysis patients may need solute permeability transport evaluation
      during acute peritonitis. The aim of this study was to assess if the simplified
      mass transfer coefficient (MTCS) or the peritoneal equilibration test (PET) was
      equivalent to the complex MTC (MTCX) in solute transport evaluation during acute
      peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We
      studied 15 episodes of peritonitis (PTIS). Results were compared to a baseline
      patient study (PRE) and a control study done 30 days after diagnosis of
      peritonitis (POST). All peritoneal evaluation methods showed a significant
      increase in solute transport during acute peritonitis compared to baseline and
      control studies. There was an acceptable correlation between MTCX and simplified
      methods including the PET in the baseline and control studies. However,
      correlation between MTCX and simplified methods decreased during acute
      peritonitis. Likewise, the PET showed a better correlation with MTCX than MTCS.
      We conclude that the PET has an acceptable agreement with MTCX even during acute
      peritonitis, so the PET can be a useful tool in evaluating peritonitis-induced
      peritoneal permeability changes.

PMID- 8534690
TI  - Frequency of various types of peritoneal catheter infections and therapeutic
      outcome of treatment.
AB  - To analyze peritoneal catheter infections (PCIs), primarily the type (acute or
      chronic), frequency, and therapeutic outcome, we assessed 113 patients treated
      between January 1992 and December 1994. The average age was 56.3 +/- 15.3 years,
      and 38% were diabetics. One hundred and thirty peritoneal catheters (PCs) were
      placed surgically in the lateral abdominal wall. The peritonitis rate fell from
      0.61 episodes/year to 0.33 episodes/year, but the exit-site and/or tunnel
      infection (ESI/TI) rate increased (from 0.48 episodes/year to 0.61
      episodes/year). Seventy-nine cases of PCI were observed; 58 (73.4%) were acute
      ESI/TI and 21 (26.6%) were exacerbations of chronic ESI/TI. Thirty-one (53.4%)
      acute PCIs were cured, 17 (29.3%) became persistent, and in 10 (17.2%) cases the
      PC was removed. In chronic ESI/TI, of the 21 exacerbations registered, in 12
      cases (57.1%) conservative treatment was effective, while in 9 cases (42.9%) the
      PC was removed. We conclude that ESI/TIs are the most frequent type of continuous
      ambulatory peritoneal dialysis (CAPD) infection and the more frequent cause of PC
      removal compared to peritonitis (p < 0.001). PC removal is more frequent in
      chronic than in acute ESI/TI (p < 0.005). The progression of infection towards
      the external and even the internal cuff is a poor prognostic sign. Staphylococcus
      aureus and Pseudomonas aeruginosa were the most common causes of infection and
      the most serious infective agents, causing chronic infection or catheter removal.
      Clinical evaluation of ESI/TI can be helped significantly by ultrasound
      examination, which is 100% positive in chronic ESI/TI and not more than 52.1%
      positive in acute ESI/TI (p < 0.005).

PMID- 8534691
TI  - Functional properties of mesothelial cells after prolonged exposure to dialysate
      effluent.
AB  - The authors tested in vitro the effect of glucose-based and amino acid-based
      dialysate effluent on the function of human peritoneal mesothelial cells. After 9
      days of exposure to the tested effluents with medium (1:1 v/v) or to a medium
      supplemented with 10% fetal calf serum (FCS) (control), several functional
      properties of the cells were studied. The synthesis of DNA measured by
      incorporation of 3H-methyl-thymidine was higher in mesothelial-cell monolayers
      exposed to the dialysates than in the controls. Synthesis of hyaluronic acid was
      similar in all three groups, but after stimulation with Il-1 the cells exposed to
      the dialysates produced more hyaluronic acid. Synthesis of tissue plasminogen
      activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was higher in the
      control cells. However, after stimulation with IL-1, the cells exposed to the
      dialysate showed greater synthesis of PAI-1 than of t-PA. Also, procoagulant
      activity of the control cells was higher than that of the cells exposed to the
      dialysates. We have concluded that the functional properties of the mesothelial
      cells may be altered in vitro during prolonged exposure to the dialysate,
      something that may also occur in vivo.

PMID- 8534692
TI  - The effect of ultraviolet rays on the prevention of exit-site infections.
AB  - The aim of this study was to show that ultraviolet (UV) irradiation to the skin
      around the catheter exit site (ES) could inhibit its infection. First, bacterial
      cultures of swabbed fluid from the ES were obtained from 68 continuous ambulatory
      peritoneal dialysis (CAPD) outpatients six times during the 24-month observation
      period. Second, the bactericidal effects of UV irradiation on the catheter ES
      were examined. The results were as follows: (1) In spite of disinfection of the
      catheter ES by the strict application of povidone-iodine once or twice a day, 23%
      45% of the cases were found to be micro-organism positive. The most prevalent
      micro-organisms from the catheter ES were, in order of highest to lowest
      prevalence, Staphylococcus epidermidis (SE), Staphylococcus aureus (SA), and
      Pseudomonas aeruginosa (PA). (2) In the nasal cavity SA was detected in 20%-25%
      of patients. There was a high incidence of ES infection among the SA nasal
      carriers. (3) UV irradiation was performed in 18 cases that constantly revealed
      bacteria on culture at the catheter ES. Ten cases (55%) became culture-negative,
      3 cases showed a microbial decrease, and 5 cases remained unchanged. These
      results suggest that UV irradiation can eliminate bacteria and can be of
      prophylactic use for ES infections.

PMID- 8534693
TI  - Subcutaneous cuff removal in persistent exit-site/tunnel infections in peritoneal
      dialysis.
AB  - The purpose of this study was to analyze catheter outcome of persistent exit
      site/tunnel infections (ESI/TIs) in peritoneal dialysis patients who underwent
      removal of the subcutaneous cuff due to persistent ESI/TI from January 1989 to
      June 1994. One hundred and sixty-eight patients (98 male, 70 female) from our
      tertiary university hospital underwent 177 double-cuff coiled Swan neck catheter
      implantations surgically. Nineteen patients (11%) had persistent ESI/TIs for more
      than 6 months. Thirteen persistent ESI/TIs responded to subcutaneous cuff
      removal. One hundred and fifty-four episodes of ESI/TI in 168 patients were
      observed over 3189 patient-months (0.58 episodes/patient-year). Nineteen patients
      (11%) had persistent ESI/TI with Staphylococcus aureus in 12 and Pseudomonas
      aeurginosa in 7 patients without episode of peritonitis except 2 patients with
      Staphylococcus aureus. Thirteen persistent ESI/TI resolved after subcutaneous
      catheter removal without catheter loss, 8 with Staphylococcus aureus and 5 with
      Pseudomonas. Sixteen catheters were lost due to fungal peritonitis and two
      secondary to recurrent bacterial peritonitis. None of the catheters were removed
      as a result of ESI/TI and related peritonitis. Subcutaneous cuff removal in
      persistent ESI/TI in peritoneal dialysis patients can significantly reduce
      catheter loss related to ESI/TI.

PMID- 8534694
TI  - Two years of experience with a new device system: a multicenter study.
AB  - Peritonitis is a crucial complication of peritoneal dialysis. Over the last few
      years, new device systems have been developed to reduce episodes of peritonitis
      caused by exogenous contamination. Remarkable improvement has been obtained by
      modifying the original connection between the catheter and the bag with the
      introduction of the Y-set. The aims of this study were to test the reliability
      and simple use of a double-bag system without disinfectant in-line (Gemini,
      Gambro) and to evaluate the incidence of peritonitis in a 2-year period of follow
      up. In a group of 167 patients, enrolled in 14 dialysis units in Italy, with a
      follow-up of 2433 patient-months, we observed 82 episodes of peritonitis in 52
      patients, with a cumulative incidence of 1 episode every 29.7 patient-months. At
      12 months the percentage of patients peritonitis-free was 69.7%, and at 24 months
      it was 62.8%. The training to complete the bag exchange, assessed by patient and
      nursing staff, was defined as "easy" in 61% of the cases and "difficult" in only
      12% of the cases. The percentage of patients requiring a partner was 23%. For
      patients this device system presents easy handling in terms of the bag exchange,
      and it may prevent peritonitis.

PMID- 8534695
TI  - Infection rates in end-stage renal disease patients treated with CCPD and CAPD
      using the UltraBag system.
AB  - Previous studies have shown the incidence of peritonitis to be generally lower
      for patients performing continuous cycling peritoneal dialysis (CCPD) than
      patients maintained on continuous ambulatory peritoneal dialysis (CAPD). Recent
      changes in CAPD techniques, particularly the introduction of the UltraBag system,
      have resulted in a marked decrease in peritonitis rates in CAPD patients. The
      purpose of the present study was to compare peritoneal dialysis-related
      infections in 73 patients treated with CCPD and 57 patients treated with CAPD
      using the UltraBag system for a 12-month period. Demographic data of the two
      groups were comparable. Peritonitis rates were significantly lower in the
      patients treated with CAPD on the UltraBag (one infection/23 patient-months) than
      in patients treated with CCPD (one infection/14.4 patient-months, p < 0.05). Exit
      site infections were also significantly lower in patients treated with CAPD (one
      episode/35 patient-months) compared to patients treated with CCPD (one
      episode/11.5 patient-months, p < 0.05). The spectrum of organisms causing
      infection was similar in both groups of patients. The study suggests that
      peritonitis and exit-site infections are significantly less common in patients
      treated with CAPD with the UltraBag system than in patients treated with CCPD.

PMID- 8534696
TI  - Neisseria meningitidis peritonitis in a CAPD patient: first case report and
      review of the literature.
AB  - Only 15 cases of any etiology of Neisseria meningitidis peritonitis have been
      reported in the world literature since the first case in 1917. We report the
      first case in a continuous ambulatory peritoneal dialysis (CAPD) patient
      presenting with abdominal pain and cloudy peritoneal dialysis fluid. A lumbar
      puncture was normal. The patient died despite therapy with ceftriaxone. Autopsy
      confirmed this was a case of primary N. meningitidis peritonitis. Of the 15 cases
      of N. meningitidis reported as a cause of peritonitis, 9 patients were less than
      age 35 with no underlying diseases. Five cases were associated with cirrhosis or
      alcohol abuse. Two cases were associated with meningitis, and 1 patient was on
      steroid therapy for systemic lupus erythematosus. Nine of 15 patients recovered.
      In conclusion, N. meningitidis should be considered as another rare cause of
      peritonitis in patients on CAPD.

PMID- 8534697
TI  - Successful treatment of fungal peritonitis with intracatheter antifungal
      retention.
AB  - Two patients who developed fungal peritonitis after receiving continuous
      ambulatory peritoneal dialysis (CAPD) for various periods were successfully
      treated with intracatheter retention of amphotericin B 1-2 mg and oral
      flucytosine or fluconazole 50 mg b.i.d. for 5 weeks. The catheter was not removed
      and efficient peritoneal permeability was maintained. We suggest that
      intracatheter retention of antifungal agents to sterilize the catheter with
      simultaneous oral antifungal agents be used to eradicate peritoneal infection.
      The catheter may not have to be removed, and CAPD can be accomplished. Period of
      hospitalization may be shortened, and the efficiency of CAPD can be maintained.

PMID- 8534698
TI  - Treatment of recurrent and resistant CAPD peritonitis by temporary withdrawal of
      peritoneal dialysis without removal of the catheter.
AB  - Recurrent and resistant continuous ambulatory peritoneal dialysis (CAPD)
      peritonitis is usually treated by removal of the catheter and temporary
      hemodialysis. We treated 3 patients: 1 with resistant Klebsiella peritonitis and
      2 with recurrent peritonitis (one due to Staphylococcus and the other to
      Enterococcus), by stopping CAPD for a 2-4 week period, leaving the catheter in
      situ and continuing antibiotic therapy. All 3 patients had resolution of their
      infections and restarted CAPD. This therapeutic modality reduced catheter
      replacements, limited admissions to the hospital, reduced psychological impact,
      and diminished risks and costs of CAPD.

PMID- 8534699
TI  - A prospective randomized comparison of single versus multidose gentamicin in the
      treatment of CAPD peritonitis.
AB  - There is an increasing trend towards the use of aminoglycosides in a once-daily
      dose administration for the treatment of severe infections in nonrenal failure
      patients. The use of once-daily dose aminoglycoside therapy may be associated
      with a reduction in toxicity. We performed a prospective randomized study
      comparing once-daily versus multiple-dose gentamicin in the treatment of
      continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Seventy-three
      patients with 100 new episodes of peritonitis were enrolled in the study. At
      presentation of peritonitis, the patients were alternately assigned to receive
      either intraperitoneal gentamicin at a dose of 40 mg/2 L dialysate administered
      as a once-daily dose or gentamicin at a dose of 10mg/2 L dialysate administered 4
      times per day. All patients also received intraperitoneal vancomycin at a dose of
      1 g per week. There were no significant differences in the treatment success (88%
      vs 82%, p = NS) and relapse (18% vs 20%, p = NS) rates between the once-daily
      dose and multiple-dose groups. The mean trough serum gentamicin level was higher
      in the once-daily dose group compared to the multiple-dose group (0.75 +/- 0.72
      vs 1.50 +/- 1.40 mg/L). In conclusion, gentamicin administered in a once-daily
      dose is as effective as multiple-dose administration in the treatment of CAPD
      peritonitis. The lower gentamicin level with once-daily dose administration may
      be associated with a reduction in aminoglycoside toxicity.

PMID- 8534700
TI  - The efficacy of intraperitoneally administered gentamicin and rifampin as initial
      treatment of peritoneal dialysis-related peritonitis.
AB  - For the initial treatment of peritonitis complicating peritoneal dialysis (PD),
      we use intraperitoneally administered gentamicin (broad spectrum and low costs)
      and rifampin (intracellular bactericidal activity). In order to assess the
      efficacy of this treatment, the outcome of 248 suspected episodes of peritonitis
      (abdominal pain, cloudy effluent, and a leukocyte count over 100/mm3) was
      evaluated. Of 227 cases with a positive culture of the PD effluent, one bacterial
      species was cultured in 188 cases (75.8%), more than one in 32 cases (12.9%), and
      in 7 cases (2.8%) yeasts. In 87.2% of the culture-positive cases, a good clinical
      response to the initialized antibiotic therapy was found. In 20 cases (8.1%)
      antibiotic treatment was discontinued within one week because no micro-organisms
      were cultured. In one case no effluent was cultured. Although in vitro resistance
      or indifference to both antibiotics was found in 45 cases (19.8%), in only 29
      culture-positive cases (12.8%) the clinical condition did not improve on initial
      therapy. Of the peritonitis episodes in which micro-organisms resistant to both
      antibiotics were cultured, 23 were Staphylococcus epidermidis, 5 were E. coli, 7
      were yeasts, and there were miscellaneous (mostly enteral) bacteria in 10 cases.
      In the studied period no significant changes were found in the susceptibility of
      the cultured microorganisms to gentamicin and rifampin. Susceptibility profile
      per episode, however, showed an increasing resistance against both antibiotics.
      It is concluded that the combination of gentamicin and rifampin as initial
      treatment of peritonitis is effective in most (87%) cases.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8534701
TI  - Preliminary evaluation of silver-coated peritoneal catheters in rats.
AB  - Silver is known to have powerful antibacterial properties against a variety of
      micro-organisms and has a low toxicity and a favorable biocompatibility profile.
      This study was designed to evaluate the effectiveness of silver-coated catheters
      in preventing early exit-site infection and to assess tunnel morphology. Seven
      male Sprague-Dawley rats underwent simultaneous implantation of two double
      cuffed, silver-coated silicone rubber and standard silicone rubber catheters.
      Weekly observations and photographs documented exit-site characteristics. The
      animals were sacrificed and catheters removed and processed for histopathology of
      the external tunnel at 5 weeks. Exit sites of silver-coated catheters tended to
      have less inflammation and infection and healed better than those of uncoated
      catheters; however, these data did not achieve significance using the Wilcoxon
      signed-rank test. Sections of the external tunnel of well-healing exit sites
      showed an epithelialized tract with granulation tissue near the cuff and
      significant invasion of the external cuff by collagen with a mild neutrophilic
      inflammatory response. In contrast, the histology of the external tunnel of
      infected exists revealed exudate overlying inflammatory granulation tissue and a
      variable degree of fibrosis of the cuff. When the exit sites appeared similar, no
      significant histopathological differences in sinus tract and cuff morphology were
      noted with either silver or standard catheters. In conclusion, these findings
      suggest that silver coating of catheters may decrease the incidence of early exit
      site infections and allow better ingrowth of the catheter.

PMID- 8534702
TI  - MCP-1 levels are elevated in peritonitis fluid from CAPD patients due to
      secretion by peritoneal macrophages.
AB  - The migration of leukocytes, including polymorphonuclear neutrophils and
      monocytes, into the peritoneal cavity is a key event of intraperitoneal
      inflammation. We investigated the levels of two members of the chemokine family,
      interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), in the
      dialysate effluent of 18 continuous ambulatory peritoneal dialysis (CAPD)
      patients with peritonitis and compared them with chemokine levels in noninfected
      CAPD effluent. Being a major source of inflammatory cytokines, we also isolated
      peritoneal macrophages from peritonitis effluent to determine the mRNA expression
      directly after isolation. The mean (SEM) concentrations of IL-8 and MCP-1 were
      significantly higher in the effluent of peritonitis patients than in noninfected
      effluents MCP-1: 22.5 +/- (6.27) versus 0.37 +/- (0.1) ng/mL and IL-8: 2.39 +/-
      (1.15) versus 0.04 +/- (0.01) ng/mL. Northern blot analysis of isolated effluent
      macrophages revealed strong signals for MCP-1 and IL-8. Our findings showed that
      CAPD effluent from patients with peritonitis contains markedly elevated MCP-1 and
      IL-8 levels, suggesting that these chemokines participate in leukocyte
      recruitment during CAPD peritonitis. Isolation of mRNA of peritonitis-derived
      peritoneal macrophages revealed strong signals for MCP-1 and IL-8, suggesting
      that macrophages are a major source of these inflammatory mediators.

PMID- 8534703
TI  - A longitudinal in vitro antimicrobial evaluation of two silver polymer surface
      treatments for peritoneal dialysis catheters.
AB  - The oligodynamic effect of silver has been utilized in medicine for many decades.
      This study evaluated the antimicrobial properties of two silver polymer surface
      treatments over 9 months to assess their usefulness for chronic percutaneous
      access. Silicone catheters were either dip-coated with micronized silver oxide in
      a silicone matrix (AgX) or impregnated with silver using an ion beam deposition
      process (Spire Argent I). Four-inch (10-cm) segments were shaken continuously in
      10 mL minimum essential media (MEM) with 2% fetal bovine serum (FBS) at 25
      degrees C. The medium was replaced weekly. Monthly eluate samples were assayed
      for Ag+ concentration using ICP atomic emission spectroscopy. Bimonthly, segments
      were removed, placed in fresh medium inoculate with 10(5) colony-forming units
      (cfu)/mL Staphylococcus aureus ATCC 25923 and quantitated over 24 hours for
      bacterial survival/growth. Relative to control catheters, there was a mean log10
      reduction of S. aureus of 4.4 with AgX and 1.7 with Spire Argent I persisting
      over the 9-month study period. Silver ion elution followed a biphasic pattern
      with both coatings establishing a steady state of 0.2 ppm at 4 months. These data
      suggest that the test surface coatings employed will deliver long-term
      oligodynamic activity when implanted percutaneously.

PMID- 8534704
TI  - A new porous surface modification technology for peritoneal dialysis catheters as
      an exit-site cuff to reduce exit-site infections.
AB  - Catheter exit-site infection continues to be a more common morbid event in
      patients undergoing peritoneal dialysis. Previous attempts to place a
      biointegration material at the next site have failed to reduce infection rates.
      This study reports the use of an innovative microporous silicone material placed
      as a cuff around the catheter at the exit site. The porous material has a pore
      sized distribution that stimulates and facilitates capillary ingrowth into the
      pores. This capillary ingrowth prevents scar tissue formation, increases blood
      supply, and theoretically improves the immunological competence of the tissue at
      the vulnerable exit site. Twenty-five test catheters (12 using standard exit-site
      creation and 13 using the Moncrief-Popovich implantation technique) were
      implanted in a canine model. The exit-site infection rate in a canine model
      without the microporous material was 100% at 2 months. The corresponding results
      with the microporous material was 40% at 2 months. The majority of the test
      catheters showed progressive drying and healing at the exit site. Sixty percent
      of the catheters healed quickly and remained infection-free. Biointegration of
      the microporous material at the exit-site was demonstrated. Several exit site
      infections with the test catheters treated only with local therapy (without
      systemic or topical antibiotics) demonstrated progressive healing and secondary
      adequate biointegration. Because of these encouraging results, human studies were
      initiated, with the first human implant occurring in August, 1994. A 10-patient
      project is planned for the next year.

PMID- 8534705
TI  - Unblocking peritoneal dialysis catheters with a combination of urokinase and
      Fogarty catheter manipulation.
AB  - The authors report three cases of peritoneal dialysis catheter obstruction in
      children. The catheters were successfully cleared by a combination of urokinase
      and Fogarty catheter manipulation. This technique can be used to clear fibrin and
      omentum from obstructed peritoneal dialysis catheters.

PMID- 8534706
TI  - Stiff wire manipulation of peritoneal dialysis catheters.
AB  - From January 1989 to June 1994 we examined the success rate of fluoroscopically
      guided stiff wire manipulation of malfunctioning peritoneal dialysis catheters
      (PDCs) at St. Paul's Hospital, Saskatoon. There were 341 (201 male, 140 female)
      patients with a PDC. There were 118 manipulations (70 initial, 48
      remanipulations) for malposition, fibrin clot, or kinked catheter. Single-cuff
      Tenckhoff catheters accounted for 95% of manipulated PDCs. No complications
      including peritonitis, exit-site infections, ruptured catheter, or bowel
      perforation were reported postmanipulation. A successful manipulation was defined
      as a functional PDC at 30 days postmanipulation. There was an overall success
      rate of 64%-67% for initial manipulations (IM) and 48% for remanipulations (RM).
      Ninety percent of those PDCs requiring IM occurred within 42 days of surgical
      insertion. RM occurred on average 55 days after IM. There were no risk factors
      identified that predisposed patients for PDC manipulation. This success rate for
      combined IM and RM of PDCs is higher than those rates quoted in the literature
      (27%-42%). We conclude that fluoroscopically guided stiff wire manipulation of
      PDCs, including repeated attempts, is a safe and effective way of prolonging PDC
      life, thus avoiding the risks of repeated surgery, improving quality of life, and
      decreasing health care costs.

PMID- 8534707
TI  - Improved training techniques and UltraBag system resulted in lowered peritonitis
      rate in an inner-city population.
AB  - Fifteen continuous ambulatory peritoneal dialysis (CAPD) patients from our
      dialysis unit were studied while using two different types of exchange systems: a
      snap-disconnect Y-set system and the Baxter UltraBag system. The incidence of
      peritonitis in the snap-disconnect Y-system was found to be 32 cases in 187
      months, or a rate of 1 case of peritonitis every 5.8 months. When these patients
      switched to the Baxter UltraBag system, the incidence of peritonitis dropped to 4
      cases in 175 months, or 1 case every 43.8 months, a highly significant
      difference. We conclude, therefore, that the UltraBag system is highly effective
      in reducing the incidence of peritonitis in CAPD patients.

PMID- 8534708
TI  - Dialysis-related amyloidosis in a large CAPD population.
AB  - We studied 212 patients from 13 Italian dialysis centers to evaluate the clinical
      aspects of dialysis-related amyloidosis in continuous ambulatory peritoneal
      dialysis (CAPD). The mean age was 64.2 +/- 12.3 years and mean time on dialysis
      was 36.9 +/- 25.1 months. Residual diuresis was 615.7 +/- 554.0 mL/day and plasma
      beta 2-microglobulin (beta 2M) level was 27.0 +/- 12.8 mg/L. Radiological
      skeletal examination, neurological problems related to beta 2M, and urinary and
      dialytic balance of beta 2M were evaluated. Correlations between age, time on
      dialysis, residual diuresis, beta 2M plasma levels, beta 2M peritoneal and renal
      removal, carpal tunnel syndrome, and bone disease were studied. Only the number
      of bone lesions had a significant positive correlation with patient age and
      negative correlation with residual diuresis. The latter had an inverse relation
      with beta 2M plasma levels. Dialytic age did not correlate with any of the
      parameters. No other correlation was observed. Hand lesions were found in 85% of
      patients with bone dialysis-related amyloidosis. In conclusion, residual diuresis
      in our patients played a positive role in the number of bone localizations. Only
      age, but not time on dialysis, had a positive impact on the bone lesions. The
      high percentage of hand lesions suggests that the observation of this skeletal
      segment is a simple, safe, and effective modality of bone follow-up for dialysis
      related amyloidosis.

PMID- 8534709
TI  - Pituitary dysfunctions in uremic patients undergoing peritoneal dialysis: a cross
      sectional descriptive study.
AB  - Several hormonal alterations have been described in patients with chronic renal
      failure. However, there are few epidemiological studies on uremia-associated
      endocrine derangements, in particular in patients undergoing peritoneal dialysis
      (PD). A cross-sectional descriptive study was performed to assess the prevalence
      of hormonal dysfunctions affecting pituitary secretions in the whole population
      of patients in the PD unit of our hospital. The total population included 69
      patients, 66 on continuous ambulatory PD and 3 on continuous cycling PD. There
      were 31 men and 38 women, the mean age was 55 years (range 23-82 years), and the
      mean duration of PD was 32 months (range 1-161 months). There were 27 (39.1%)
      patients with diabetes mellitus (7 type I and 20 type II). Clinical records were
      reviewed for hormonal alterations affecting the pituitary and its target glands.
      The whole population had available data on the pituitary-thyroid axis. The
      following diagnoses and prevalences were found: hypothyrotropic hypothyroidism 4
      (5.8%), subclinical hypothyroidism 4 (5.8%), primary hypothyroidism 8 (11.6%),
      and low T3 syndrome 11 (15.9%). The remaining pituitary hormones were available
      in 20 patients. Hyperprolactinemia was found in 7 (35%) patients and abnormally
      increased growth hormone levels in 6 (30%). Gonadotropin levels were normal for
      the age of the women and showed a tendency to be increased in most of the men.
      Corticotropin levels were normal in all patients with available data. There was
      no relationship between the high prevalence of diabetes mellitus in our
      population and the remaining hormonal derangements found. These results suggest
      that there is a non-negligible prevalence of pituitary abnormalities in uremic
      patients undergoing PD.

PMID- 8534710
TI  - Thyroid function surveillance in CAPD patients.
AB  - We monitored thyroid function in 75 peritoneal dialysis patients (55 +/- 15
      years). A total of 20 (27%) were hypothyroid; 9 were diagnosed about the time of
      initiation of dialysis, and 11 prior to onset of renal failure. Thyroid function
      surveillance found an increase in serum thyrotropin (TSH) concentration to
      hypothyroid values in only one patient. On replacement therapy serum thyroxine
      was similar in euthyroid and hypothyroid patients (6.94 +/- 1.69 vs 6.52 +/- 1.65
      micrograms/dL, respectively; p = 0.380), but TSH was higher in hypothyroid
      patients (5.61 +/- 5.67 vs 2.59 +/- 1.49 microU/mL, respectively; p = 0.001).
      Serum creatinine (8.6 +/- 3.1 vs 11.4 +/- 5.1 mg/dL, respectively; p = 0.049) and
      albumin concentrations (3.76 +/- 0.47 vs 3.33 +/- 0.71 g/dL, respectively; p =
      0.006) were lower in hypothyroid than euthyroid patients. Hyperthyroid patients
      had higher serum triglyceride concentrations than euthyroid patients (306 +/- 176
      vs 189 +/- 122 mg/dL, respectively; p = 0.013). Parathyroid hormone (PTH) was
      lower in hypothyroid than normothyroid patients (108 +/- 80 vs 261 +/- 265 pg/mL,
      respectively; p = 0.032). No differences were observed in serum calcium,
      phosphorus, and alkaline phosphatase. We conclude that hypothyroidism is common
      in peritoneal dialysis patients, usually antedates dialysis therapy, results in
      lower serum albumin and creatinine concentrations and higher serum triglyceride
      concentrations, is associated with lower serum PTH concentrations, and that
      thyroid function surveillance is not necessary in the absence of symptoms
      suggestive of hypothyroidism.

PMID- 8534711
TI  - Energy metabolism during CAPD: a controlled study.
AB  - Abnormalities of energy metabolism may exacerbate the high prevalence of protein
      calorie malnutrition and inadequate calorie intake in continuous ambulatory
      peritoneal dialysis (CAPD) patients, leading to further nutritional depletion. In
      a controlled study, using indirect calorimetry, we evaluated oxygen consumption
      (VO2), CO2 production, resting energy expenditure, and respiratory exchange ratio
      (RER) in 12 CAPD patients at rest and during a standard CAPD exchange and in 11
      healthy nonuremic control patients. In addition, we investigated the influence of
      nutritional status and dialysis adequacy on energy metabolism in the CAPD group.
      There was no significant difference in resting energy parameters between the two
      groups. Unlike the control group, blood glucose and RER were maintained during
      prolonged fasting in the CAPD patients. This observation indicates that all the
      absorbed glucose was used as a metabolic fuel preventing fat oxidation. There was
      no significant relationship between energy expenditure and dialysis adequacy.
      There was no significant relationship between nutritional state (including energy
      intake) and energy expenditure despite evidence of malnutrition in 41% of the
      patients. If maintenance of "normal levels" of energy expenditure occurs in
      dialysis patients with suboptimal calorie intake (especially with evidence of
      protein-calorie malnutrition), this inability to conserve energy may act as an
      additional risk factor for ongoing malnutrition.

PMID- 8534712
TI  - Insulin-like growth factor-I in patients on CAPD and hemodialysis: relationship
      to body weight and albumin level.
AB  - The relationship between insulin-like growth factor-I (IGF-I), body weight, and
      serum albumin was studied in 17 patients on continuous ambulatory peritoneal
      dialysis (CAPD) and 17 patients on hemodialysis. Patients were matched for
      gender, age (33-83 years), body mass index (16.7-36.1 kg/m2), hematocrit,
      concentrations of serum growth hormone, and duration of dialysis (1-210 months).
      Serum IGF-I concentration was measured by radioimmunoassay (Incstar) and albumin
      by a standard laboratory technique. CAPD patients had significantly lower serum
      albumin concentrations than hemodialysis patients, whereas IGF-I levels in the
      two groups were similar and did not differ from those in 18 normal subjects. We
      did not find significant positive correlations between IGF-I and serum albumin
      levels in CAPD or in hemodialysis patients. On the other hand, IGF-I showed a
      strong positive correlation with body weight (for the CAPD group r = 0.523; for
      both groups together r = 0.493). Both groups (CAPD and hemodialysis) and CAPD
      patients who weighted less than 60 kg (44%) had significantly lower serum IGF-I
      levels (113.5 +/- 10.2 and 108.8 +/- 15.7 micrograms/l +/- SEM, respectively)
      than patients who weighed 60-80 kg (38.3%; 181.2 +/- 20.9 and 196.6 +/- 27.2
      micrograms/L +/- SEM, respectively) or above 80 kg (17.6%; 205.2 +/- 37.7 and
      229.5 +/- 43.5; micrograms/L +/- SEM, respectively). It therefore appears that a
      low serum IGF-I level is a better indicator of malnutrition in CAPD and
      hemodialysis patients than low serum albumin.

PMID- 8534713
TI  - Inhibition of mesothelial cell growth and protein synthesis by heparin.
AB  - Heparin, routinely used in peritoneal dialysis, has been found to have various
      effects, mainly inhibitory. Its infusion into the peritoneal cavity may adversely
      affect mesothelial cell growth and regeneration. Thus we wished to determine if
      heparin inhibits mesothelial cell growth and is does-dependent. Rat mesothelial
      cells were incubated for 3 days and 6 days with 200, 100, 20, 2, and 0.5 U/mL of
      heparin. Cellular proliferation and protein synthesis were determined by liquid
      scintillation counting after 24-hour pulses with 3H-thymidine and 3H-leucine.
      Heparin at 2 and 0.5 U/mL had no significant effect on radionuclide uptake. At
      100 U/mL heparin inhibited radionuclide uptake by at least 50%. These findings
      indicate that heparin in small concentrations may be harmless, but at higher
      concentrations is inhibitory to mesothelial cell growth and proliferation.

PMID- 8534714
TI  - Collagen markers in peritoneal dialysis patients.
AB  - Possible relationships between the dialysate-to-plasma creatinine equilibration
      ratio (D/Pcreatinine 4 hour), duration of peritoneal dialysis treatment, number
      of peritonitis episodes, and mass appearance rates of three connective tissue
      markers [carboxyterminal propeptide of type I procollagen (PICP), aminoterminal
      propeptide of type III procollagen (PIIINP), and carboxyterminal telopeptide of
      type I collagen (ICTP)] were studied in 19 nondiabetic peritoneal dialysis
      patients. The absence of correlation between the mass appearance rates of the
      markers and the duration of dialysis treatment as well as the number of
      peritonitis episodes supports the concept that peritoneal dialysis does not cause
      persistent changes in the deposition and degradation rates of collagen. A
      correlation between the D/Pcreatinine 4 hr and the PICP mass appearance rates was
      found. Since it is unlikely that transperitoneal transport alone is responsible
      for the appearance of PICP in dialysate, this might reflect an association
      between a large peritoneal surface area and the amount of submesothelial
      connective tissue.

PMID- 8534715
TI  - Cross-sectional analysis of erythropoietin use in CPD: its relation to azotemic
      index clearances.
AB  - The association between the use of erythropoietin and urea or creatinine
      clearance was studied in two populations on continuous peritoneal dialysis (CPD)
      residing either at an altitude of 1600 m (n = 194) or at sea level (n = 108).
      Among peritoneal and total KT/V urea and creatinine clearance (CCr) indices, only
      total CCr was lower in the high altitude group receiving erythropoietin than in
      the corresponding group not receiving erythropoietin (68.0 +/- 34.9 vs 82.9 +/-
      40.9 L/1.73 m2 weekly, p < 0.01). However, 24-hour urine volume and urinary KT/V
      urea and CCr were consistently lower in the groups receiving erythropoietin than
      in those not receiving erythropoietin. Total weekly KT/V urea < or = 1.70 and CCr
      < or = 52 L/1.73 m2 were considered indicators of inadequate CPD. Although the
      percent of patients receiving erythropoietin did not differ overall between
      groups with adequate and those with inadequate CPD, a trend towards more frequent
      use of erythropoietin was found in the sea level group with inadequate CCr versus
      the group with adequate CCr (28.2% vs 16.9%, p = 0.084). In CPD decreased renal
      function is associated with more frequent use of erythropoietin. Whether
      inadequate total urea or creatinine clearance is also associated with more
      frequent erythropoietin use requires further study.

PMID- 8534716
TI  - The identification of bone mineral density in CAPD in comparison with HD
      patients.
AB  - Renal osteodystrophy is a virtually universal complication of chronic renal
      failure (CRF). Varying degrees of calcium-phosphate metabolism derangement and
      different types of skeletal damage are observed in CRF for many reasons while the
      use of dialysis for the management of end-stage renal failure further affects
      these complications. This study was designed to evaluate the bone mineral density
      (BMD) that is measured by dual-energy x-ray in three groups of patients: A, 10
      patients on continuous ambulatory peritoneal dialysis (CAPD); B, 10 patients on
      hemodialysis (HD); and C, 10 predialytic patients with advanced CRF. All patients
      were matched for age, sex, duration of dialysis (> 3 years), and the use of
      phosphate binders. Biochemical (serum iPTH levels, SAP, Ca, P) and radiological
      bone studies were compared in the three groups. The majority of predialytic
      patients had BMD values within the normal range, while the BMD values in PD
      patients were higher (0.985 g/cm2) in comparison with HD patients (0.949 g/cm2).
      Some patients, especially in the HD population, showed an increase in BMD with
      time on dialysis. From all other comparisons, radiological signs of high turnover
      bone disease and osteopenia were the only variables that were correlated with
      BMD. All these findings suggest that dialysis affects the bone status and that
      CAPD patients have better bone mineral metabolism as shown mainly with the use of
      BMD measurements.

PMID- 8534717
TI  - Decreasing the complications of renal osteodystrophy secondary to high phosphorus
      levels by using an innovative self-monitoring educational program.
AB  - We wanted continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling
      peritoneal dialysis (CCPD) patients to become more cognitive of the complications
      of high-serum phosphorus levels (> 6.0 mg/dL). The phosphorus self-monitoring
      program was designed to encourage patients to be more responsible for preventing
      the complications of renal osteodystrophy. Patients' phosphorus levels were
      graphed monthly on a poster in the exam room. Additional posters discussed their
      responsibilities to control phosphorus and the complications associated with
      hyperphosphatemia. All patients received an informative letter regarding the
      inception of the program in March 1994 and also were assured total anonymity of
      their laboratory results. At monthly clinic appointments, they received
      additional written information on phosphorus and discussed their phosphorus
      levels. Our teaching method proved effective in our CAPD/CCPD population. In
      March 1994, 31% of our patients had a phosphorus level greater than 6.0 mg/dL
      versus 10% in September 1994. The ability of patients to see their monthly
      progress and the comparison with other patients encouraged much interest and
      questions regarding phosphorus control.

PMID- 8534718
TI  - Recombinant human growth hormone (rhGH) in dialysis patients: update 1995.
AB  - The use of recombinant human growth hormone (rhGH) in patients undergoing
      dialysis has not received substantial investigation. The available data would
      indicate that short-term growth velocity is improved with rhGH in children
      undergoing both peritoneal dialysis and hemodialysis. However, definitive
      assessment awaits long-term controlled studies. Although definitive studies are
      lacking, it does not appear that there is a differential effect of rhGH in the
      various dialytic modalities. Compared to patients with chronic renal
      insufficiency, the response to rhGH treatment in children undergoing dialysis
      appears inferior; however, definitive data are also lacking. rhGH is effective
      when administered intraperitoneally; however, long-term studies are required to
      substantiate efficacy. In summary, despite limited data, rhGH appears to be
      effective in growth-retarded children undergoing dialysis.

PMID- 8534719
TI  - Outcome of infants on chronic peritoneal dialysis.
AB  - To assess the outcome of infants on chronic peritoneal dialysis (PD), we
      retrospectively reviewed 21 patients who began PD prior to one year of age. Mean
      age at first dialysis was 56 +/- 56 days with mean weight of 3.6 +/- 1.6 kg.
      Seventeen infants were male and 17 were Caucasian. The most common primary renal
      diagnosis was renal hypoplasia/dysplasia, occurring in 7 infants. Mean time on PD
      was 10 +/- 10 months. Eleven infants had oliguria, and 10 infants had adequate
      urine output. All but 1 infant received tube feedings; mean caloric intake was
      453 +/- 92 kJ/kg/day. Despite nutritional management, weight, height, and head
      circumference was at or above the fifth percentile in only 10, 4, and 5 infants,
      respectively. Nonrenal abnormalities were present in 12 of 21 infants with lung,
      heart, and central nervous system abnormalities occurring most often. Outcome
      included 7 receiving renal transplants, 1 who recovered renal function, 4 who
      continued on PD, and 9 who died. Seven infants with oliguria died, while only 2
      infants with adequate urine output died. No infant with isolated renal disease
      died, while 9 of 12 patients with renal plus nonrenal abnormalities died. Thus
      mortality in infants less than one year of age on PD appears to be associated
      with the presence of oliguria and nonrenal abnormalities.

PMID- 8534721
TI  - Current status of pediatric home peritoneal dialysis training in the United
      States.
AB  - There are little aggregate data that examine attributes of peritoneal dialysis
      (PD) training programs for children. We determined characteristics of pediatric
      home PD training programs in a sample of 54 centers in the NAPRTCS PD registry by
      telephone interview. Sixty-seven percent of the programs trained pediatric
      patients only (P-only); 33% were combined pediatric/adult (P/A) programs; 33
      programs had dedicated training rooms. Most programs trained 5 to 8
      patients/year; only 2 trained more than 12 patients/year. Forty-eight of 54
      programs (89%) taught both automated and manual PD techniques; the preferred type
      of PD varied. All units preferred to train 2 people. The patient was often one of
      the trainees, but the minimal eligible age varied greatly. The patients were
      trained as inpatients (IP) in 38 units (70%) and as outpatients (OP) in 16 units
      (30%). P-only programs were less likely to train as OP (20%) than P/A programs
      (50%) (p < 0.01). There was no difference in the mean training time for P-only
      versus P/A programs. However, training that took more than 6 days occurred more
      often when done as an IP (79%) than as an OP (56%) (p = 0.057). Furthermore, only
      25% of IP units that took more than 6 days to train offered training on the
      weekend; none of the IP units that took more than 10 days offered weekend
      training. In conclusion, the structure of PD training programs for children in
      the United States varies tremendously. OP training is usually shorter in duration
      and potentially more cost-effective.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534720
TI  - Immunizations in children on PD: current guidelines and recommendations.
AB  - Antibody responses to currently recommended immunizations in pediatric patients
      on chronic peritoneal dialysis (CPD) have been measured and the results have been
      variable. Although the incidence of vaccine-preventable disease in pediatric CPD
      patients is not known, it appears that protection from these diseases may be
      reduced. The explanation for the abnormal response to vaccines might include
      lower seroconversion rates in these patients, with lower antibody titers or
      levels. Also a rapid decline of antibody levels or titers may occur as a
      consequence of continuous peritoneal dialysis. Specific vaccines that may result
      in a less than optimal response in pediatric CPD patients include hepatitis B
      virus, hemophilus influenza type b, measles, mumps, rubella and pneumococcal
      vaccine. Patients who receive these immunizations should be monitored closely.
      Increased vaccine dosage, reinforced vaccination schedules, as well as
      concomitantly administered adjuvant immuno-modulators may play an important role
      in more effective vaccination of pediatric CPD patients. It is important that
      vaccine response be monitored in these patients by measuring specific antibody
      titers or levels to ensure adequate protection from vaccine-preventable illness.

PMID- 8534722
TI  - Peritoneal membrane failure in children on peritoneal dialysis.
AB  - Peritoneal dialysis (PD) success depends on adequate renal function replacement.
      Reports in adult dialysis populations indicate the risk of ultrafiltration
      failure (UF) increases with the time on dialysis. Type 1 UF is the most common.
      For children, dialysis modalities are temporizing measures until renal
      transplantation, considered optimal therapy for end-stage renal disease in
      children, can be performed. Children are frequently on dialysis for less than 2
      years prior to transplantation. Thus if type 1 UF frequency increases with time
      on dialysis, it would be expected to occur less frequently in children, because
      they often are on dialysis for shorter periods. A retrospective chart review was
      performed to determine the cause of ultrafiltration failure in children; 172
      children, mean age 8.0 +/- 5.5 (SD) years received a mean of 15 +/- 11.9 (SD)
      months of chronic PD; 39 patients received only continuous ambulatory peritoneal
      dialysis, 18 received only continuous cycling peritoneal dialysis, 22 received
      only tidal PD, and 94 received more than one type of PD. Ten patients (5.8%)
      developed type 2 UF failure as sequellae of atypical peritonitis, Candida
      albicans (6 patients), Mycobacterium foruitum (2), Achromatium spp. (1), and
      Pseudomonas aeruginosa (1). There was no significant difference in time on
      dialysis for children who developed membrane failure. No patients with type 1 or
      type 3 UF could be identified. It appears that the causes of peritoneal membrane
      failure in children are different from those in adults.

PMID- 8534723
TI  - Peritoneal blood flow and peritoneal transfer parameters during dialysis with
      administration of drugs.
AB  - Effective peritoneal capillary blood flow (EPBF) was evaluated by calculating the
      diffusive mass transport coefficient of carbon dioxide during intermittent
      peritoneal dialysis (IPD) performed with the intraperitoneal administration of
      sodium nitroprusside (NP), chlorpromazine (CP), or isoproterenol (IP) in the
      doses 5, 2.5, and 0.5 mg/L, respectively. Peritoneal transfer rates of substances
      of different molecular size and charge were simultaneously examined and compared
      with EPBF. EPBF (mL/min) was 220 +/- 40 (+/- SEM) for NP (n = 11), 224 +/- 29 for
      CP (n = 10), and 243 +/- 35 for IP (n = 10). These values did not differ
      significantly from those obtained during dialysis without drugs (223 +/- 22
      mL/min, n = 20). NP, CP, and IP did not cause any significant changes in
      peritoneal transfer of carbon dioxide. Transfer rates of bicarbonate and total
      carbon dioxide were increased only with NP. All drugs enhanced the peritoneal
      removal of sodium, potassium, urea, and uric acid. Total protein loss was
      enhanced by all drugs except IP. With statistically similar EPBF during dialysis,
      the augmenting effect of NP and IP on small solute removal was the most
      pronounced. These results indicate that EPBF is not a major factor in the changes
      in peritoneal transfer rates during dialysis performed with NP, CP, or IP.

PMID- 8534724
TI  - Clinical experience in the treatment of infants with chronic peritoneal dialysis.
AB  - Chronic peritoneal dialysis (CPD) is the first treatment modality for most
      infants with end-stage renal failure; this group of patients shows peculiar
      clinical and technical problems. We present the data from a National Registry on
      22 children starting CPD under one year of age, representing 11.6% of the total
      population of the Registry (189 patients). Mean weight at start of CPD was 6.1 +/
      1.8 kg and duration of dialysis was 22.1 +/- 15.5 months. During the follow-up
      period, 9 patients were transplanted, 1 was shifted to hemodialysis, and 4 died.
      Patient survival was 89.1% and 82.2% at 1 and 2 years (97.9% and 96.5% in the
      group of 167 older children); technique survival results were 89.1% at 1 year and
      77.1% at 2 years (vs 92.5% and 85.7%, respectively). The incidence of peritonitis
      was 1 episode every 15.6 CPD-months (1:16.1 in the older children). Catheter
      related complications occurred more frequently in infants (1:11.8 vs 1:17
      episode:CPD-months), even if this difference was not statistically significant.
      Statural growth was on average -0.29 +/- 0.66 SD/year with a significant
      improvement between the first (-0.50 +/- 0.79) and the second (+0.23 +/- 0.77)
      year of CPD. Our data confirm that infants represent a higher risk group and that
      they can be treated satisfactorily with CPD while awaiting renal transplantation.

PMID- 8534725
TI  - The implementation of a continuous quality improvement program in a pediatric
      peritoneal dialysis unit.
AB  - Continuous quality improvement (CQI) principles and practices were utilized to
      evaluate the outpatient peritoneal dialysis follow-up process and the routine
      monthly laboratory testing of chronic dialysis patients. CQI enabled us to reduce
      total clinic visit time from a mean of 161 min to 90.8 min. Waiting was decreased
      from a mean of 51.6 min to 15.8 min. The number of routine monthly laboratory
      tests performed on patients undergoing chronic dialysis was also reduced,
      resulting in decreased charges of at least $429.50 per patient per month.

PMID- 8534726
TI  - Current approach to peritoneal access in North American children: a report of the
      Pediatric Peritoneal Dialysis Study Consortium.
AB  - To determine standard peritoneal access practices in North American children, a
      questionnaire was distributed to the 18 participating centers of the Pediatric
      Peritoneal Dialysis Study Consortium. The survey covered areas including catheter
      placement, postoperative catheter break-in, chronic catheter care, and treatment
      of exit-site and tunnel infection.

PMID- 8534727
TI  - Routine omentectomy is not required in children undergoing chronic peritoneal
      dialysis.
AB  - A routine omentectomy is recommended in children commencing chronic peritoneal
      dialysis, but is not routine practice in adults. We reviewed the outcome of 66
      catheters (57 straight and 9 spiral) inserted into 38 patients (median age 7.8
      years, 12 patients under 2 years) over a period of 4.8 years. The aim of the
      study was to determine whether an omentectomy affects the incidence of catheter
      blockage or peritonitis. Mean catheter life was 6.8 months (range 0.2-28 months).
      Fifteen are still in situ, and 14 were removed electively (transplantation).
      Blockage occurred in 1/22 catheters inserted after an omentectomy, compared with
      10/44 inserted without an omentectomy (absolute risk reduction with omentectomy =
      0.18). Blockage was more frequent with spiral catheters (4/9 vs 7/57; p < 0.05).
      Thirty-seven catheters were associated with one or more episodes of peritonitis.
      Peritonitis was not significantly more frequent after omentectomy. We conclude
      that a routine omentectomy is not routinely indicated in children commencing
      chronic peritoneal dialysis. Eleven omentectomies are required to prevent two
      omental blockages (1/0.18), and secondary omentectomy after blockage is a
      straightforward procedure. Spiral catheters conferred no benefit in this study.
      Omentectomy does not influence the incidence of peritonitis.

PMID- 8534728
TI  - Treatment of peritoneal dialysis-associated peritonitis with continuous versus
      intermittent vancomycin/teicoplanin and ceftazidime in children: preliminary
      results of a prospective randomized trial. Members of APN Arbeitsgemeinschaft
      Paidiatrische Nephrologie.
AB  - A recent treatment update for continuous peritoneal dialysis (CPD)-associated
      peritonitis recommends first-line use of continuously or intermittently
      administered intraperitoneal vancomycin and ceftazidine. Teicoplanin has recently
      been introduced as a potentially less toxic alternative glycopeptide antibiotic.
      However, efficacy and safety have not been demonstrated for intermittent
      treatment schedules or for the use of teicoplanin in prospective studies.
      Therefore, a prospective trial on the treatment of CPD-associated peritonitis was
      started in 15 pediatric dialysis units using vancomycin or teicoplanin, in
      combination with ceftazidine. Vancomycin or teicoplanin was administered either
      continuously with each bag of dialysate for 10 days or as a single dose on days 1
      and 8, and ceftazidime either continuously or in one bag of dialysate per day.
      Until December 31, 1994, 81 episodes of peritonitis including 16 relapses
      occurred in a cohort of 120 patients. The incidence of peritonitis was 1
      episode/13.7 months, regardless of treatment modality [continuous ambulatory
      peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD)].
      Thirty-six (57%) primary peritonitis episodes were caused by staphylococci (21
      Staphylococcus aureus, 15 coagulase-negative), 12 (19%) by gram-negative
      bacteria, 7 by other germs, and in 8 (13%) cases cultures remained sterile.
      Primary treatment response was achieved in 43/46 (93%) gram-positive and 4/12
      (33%) gram-negative peritonitis episodes. Relapses occurred only with gram
      positive bacteria (16/63, 25%). In cases of gram-positive peritonitis, no
      differences in primary response (25/25 vs 15/18) or relapse rates (10/36 vs 6/27)
      were observed between groups on continuous and intermittent treatment,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534730
TI  - The impact of exit-site care and catheter design on the incidence of catheter
      related infections.
AB  - The optimal approach to catheter exit-site care and catheter design in terms of
      catheter-related infections (e.g., exit-site infections, peritonitis) in children
      remains elusive. We retrospectively compared the incidence of exit-site
      infections and peritonitis in 33 pediatric peritoneal dialysis patients who used
      one of three exit-site care/catheter combinations. The catheters used were single
      cuffed, curled Tenckhoff (T), and double-cuffed Swan neck (SN). Exit-site care
      included either povidone-iodine (PI) or chlorhexidine (CHL) as cleansing agents.
      Our data suggest that the use of chlorhexidine versus povidone-iodine is
      associated with a significant decrease (p < 0.05) in the frequency of catheter
      exit-site infections in children. The use of the Swan-neck double-cuffed catheter
      does not appear to have any further impact on the frequency of exit-site
      infections. Neither the use of chlorhexidine nor Swan neck catheters had an
      effect on our peritonitis rate. Our review suggests that a prospective evaluation
      of a chlorhexidine-based exit-site care regimen in children should be encouraged.

PMID- 8534729
TI  - Multiple drug classes and hyperosmolarity alter binding of muscarinic drugs to
      mesothelial cells in vitro.
AB  - Mesothelial cells in vitro exhibited binding sites for L-quinuclidinyl[phenyl-4
      3H]-benzilate ([3H]-QNB), but not [3H]-N-methylscopolamine (NMS), a cell
      impermeable ligand. [3H]-QNB binding demonstrated a biphasic pattern of binding
      in living cells: a maximum after 15 min at 37 degrees C was followed by a
      decrease out to 90 min. [3H]-QNB binding was blocked by increasing concentrations
      of atropine; WIN35428 and GBR12909, dopamine transport inhibitors also decreased
      binding. Pretreatment of cells for 18 hours with atropine, QNB, or WIN35428
      resulted in enhanced [3H]-QNB binding, but coexposure to cycloheximide blocked
      this increase. Hyperosmolarity caused by NaCl or mannitol decreased binding of
      [3H]-QNB to living cells. Thus rabbit peritoneal mesothelial cells possess
      binding sites for [3H]-QNB that are influenced by other drugs and osmolarity.

PMID- 8534731
TI  - Nutritional effects of KT/V in children on peritoneal dialysis: are there
      benefits from larger dialysis doses?
AB  - Dialysis adequacy is monitored by urea kinetic modeling (UKM), in particular by
      calculation of KT/V (normalized whole body urea clearance) and PCRN (normalized
      protein catabolic rate). All children on peritoneal dialysis from our unit (7
      children; mean age 7 years, 8 months) participated in our study (dialysis
      research program of the French Registry of Peritoneal Dialysis). Every month
      analysis of dialysate and urine collections and blood samples were compared to a
      3-day diet survey to analyze the relations between doses of dialysis (KT/V) and
      nutrition [dietary protein intake (DPI) and caloric intake]. Calculated protein
      intake and DPI were also compared. Spearman correlation coefficients were used to
      assess the association between variables. KT/V values were spread over a wide
      range (0.8-2.8, mean 1.9). KT/V was positively (weakly) correlated to PCRN (p =
      0.07, y = 0.24x + 1.08, r = 0.2), but not to DPI. No correlation could be found
      between PCRN and DPI, but doses of dialysis (KT/V) were positively correlated to
      caloric intake (p = 0.001, y = 28.97x + 13.66, r = 0.424). We assume that the
      correlation between KT/V and PCRN is not necessarily the reason, but only a
      calculation effect. On the contrary, the positive correlation between KT/V and
      caloric intake allows us to speculate that more efficient dialysis enhances
      appetite.

PMID- 8534732
TI  - Pyrazinoic acid decreases peritoneal transfer rates.
AB  - It was shown elsewhere that in a peritoneally dialyzed woman with pulmonary
      tuberculosis, oral treatment with rifampicin and pyrazinamide (11 and 25
      mg/kg/day, respectively) caused a decrease in the peritoneal transport of sodium,
      potassium, urea, uric acid, protein, and ultrafiltration rate by 48% to 75%
      compared to the pretreatment values. Pyrazinoic acid (PA), a metabolite of
      pyrazinamide, may account for these changes, because rifampicin was also
      previously used in this patient without peritoneal function impairment. Thus in
      the present study the influence of PA on the human peritoneum is examined using
      the modified Ussing-type chamber. PA (1 mg/dL) was introduced into the medium on
      the interstitial side of the membrane. After the introduction of PA, uric acid
      transfer from the interstitial to the mesothelial side decreased by about 50%.
      There were no significant changes in the urea and albumin transfer rates. In
      conclusion, PA induces changes in uric acid transfer acting directly on
      mesothelial cells, whereas a decrease in the peritoneal transfer of other solutes
      may be caused by a decrease in convective transfer rates due to impaired
      ultrafiltration.

PMID- 8534733
TI  - Nitrate in stable CAPD patients and during peritonitis.
AB  - During continuous ambulatory peritoneal dialysis (CAPD) peritoneal vessels are
      dilated. Nitric oxide (NO) causes vasodilation in many organs. Nitrate, a stable
      metabolite of NO, was measured in plasma and dialysate. In 6 stable CAPD patients
      standard peritoneal analyses were performed. The mass transfer area coefficient
      (MTAC) of nitrate was 11.5 mL/min (10.0-17.0 mL/min) (median and range). The MTAC
      of creatinine was of the same order of magnitude: 10.7 mL/min (8.0-14.2 mL/min),
      although the molecular weight of nitrate is lower (62 vs 113 dalton). The
      correlation between the MTAC of nitrate and the MTAC of creatinine indicated
      diffusion from the circulation and not local production of NO (r = 0.71; p =
      0.11). Peritoneal permeability is increased in the acute phase of peritonitis,
      partly caused by extensive vasodilation. The potential role of NO during
      peritonitis was investigated in 8 CAPD patients with 11 peritonitis episodes in
      the acute phase and after recovery. The median dialysate/plasma (D/P) ratio of
      nitrate in the acute phase was 1.47 (range 0.96-2.55), which was higher than
      after recovery: 1.07 (0.99-1.75), p < 0.05. No relation was found between the D/P
      ratio of nitrate and the D/P ratio of TNF alpha (tumor necrosis factor). In
      conclusion, dialysate nitrate levels in stable CAPD patients are likely to be
      determined by diffusion from the circulation. D/P ratios exceeding 1.0 during the
      acute phase of peritonitis are probably the result of local NO production. This
      may contribute to the marked vasodilation during peritonitis.

PMID- 8534734
TI  - Hematocrit has no effect on peritoneal transport indices.
AB  - To assess the effect of hematocrit (Hct) on peritoneal transport indices (PTi),
      we studied the relationship between Hct (mean 28.1 +/- 5.1%, range 19.1-41.3%)
      and PTi with 118 peritoneal equilibration tests (PETs; 270 min, 1.36%) on 52
      stable patients on peritoneal dialysis. Furthermore, considering a Hct 30% as
      ideal in peritoneal dialysis (PD), 14 patients who had performed a PET both with
      a Hct <30% and > or = 30% were checked for any variations in the PTi and blood
      pressure. We analyzed the subsequent PTi: ultrafiltration; creatinine (Cr) and
      blood urea nitrogen (BUN) clearance and mass transfer area coefficient (MTAC);
      120, 240, and 270 min Cr D/P, UN D/P and glucose D/D0. Linear regressions between
      Hct and the PTi (118 PETs) did not prove statistically significant. The analysis
      of the PTi in 14 patients who had performed a PET with both a Hct < 30% and > or
      = 30% did not prove statistically significant, and no change in blood pressure
      was demonstrated. We do not consider Hct to have a significant influence on PTi.

PMID- 8534735
TI  - Potassium is not a good solute to estimate residual volume in CAPD.
AB  - Residual volume is defined as the volume of dialysate remaining in the peritoneal
      cavity after complete drainage of fluid. In this study the residual volume was
      estimated in 9 patients, age 42 +/- 9 years, on continuous ambulatory peritoneal
      dialysis (CAPD) for 14 +/- 12 months, using two different solutes: dextran 70 and
      potassium. The residual volume was calculated from the change induced in drain
      dialysate solute concentration by the known volume and solute concentration of
      the newly infused dialysis solution. The residual volume estimated with dextran
      70 was 195 +/- 105 mL (75-375 mL) and with potassium 411 +/- 108 mL (245-596 mL)
      (K > D, p < 0.001). The correlation between these two measurements was close to
      significance (r = 0.654; p = 0.056). In conclusion, potassium overestimates the
      residual volume, probably because of its rapid diffusion during the infusion
      time.

PMID- 8534736
TI  - Rat model of peritoneal fibrosis: preliminary observations.
AB  - The aim of this study was to establish a rat model of peritoneal fibrosis. After
      insertion of peritoneal catheters into 18 rats, the rats were divided into three
      groups. All animals were dialyzed twice a day with 4.25% Dianeal containing
      heparin. Group 1 rats (control) received antibiotics (vancomycin and gentamicin)
      in each exchange: group 2 rats were inoculated with Escherichia coli (5 x 10(6)
      in 5 mL of saline) at the beginning of the study; group 3 rats were treated with
      antibiotics after Escherichia coli inoculation; they also received a second
      inoculation of Escherichia coli after the second week of the study. By the end of
      the second week, group 2 rats were sacrificed because of catheter problems. Group
      1 and 3 rats were sacrificed after 4 weeks of dialysis. A weekly peritoneal
      equilibration test (PET) was performed in each rat. The comparison of the PET
      results from the beginning and end of the study showed an increased permeability
      to glucose (p < 0.05) and total protein (p < 0.05) in group 3, which was not
      noted in group 1. In histology samples there was only delicate fibrosis with
      cellular infiltration in the peritoneum in group 1 rats. These changes were much
      more prominent in group 3 rats. This study suggests that E. coli peritonitis
      causes peritoneal fibrosis in rats, but to have a sclerosing encapsulating
      peritonitis (SEP) model this experiment must be carried out for a longer time.

PMID- 8534737
TI  - Spontaneous peritonitis and peritoneal fibrosis in rats on peritoneal dialysis
      for 9 weeks.
AB  - To investigate characteristics of peritonitis in rats on peritoneal dialysis
      (PD), we retrospectively studied 36 cases of peritonitis in 23 rats. After
      breakin dialysis postcatheter insertion, the animals were dialyzed twice daily
      with 1.5% or 4.25% Dianeal for 8 weeks. White blood cell (WBC) count with
      differentials and microbiological culture of the dialysate were examined twice
      weekly. Peritonitis was treated with cefazolin and tobramycin until the tenth day
      after the dialysate became clear. The peritoneal equilibration test (PET) was
      performed at weeks 2, 6, and 10. The dialysate was obtained at 0, 2, and 4 hours
      for glucose assay. The peritoneal cavity was inspected, and peritoneal tissue
      specimens were taken. There were 10 single episodes of peritonitis, 7
      recurrences, and 6 reinfections. The organisms isolated were Staphylococcus
      aureus in 24 cases of peritonitis and Escherichia coli in 6 cases of peritonitis.
      The average treatment period was 16 days. The glucose absorption ratio became
      higher over time in single episodes of peritonitis, but was unchanged in
      recurrences and reinfections. Sixteen adhesions, 1 abscess, and 12 sclerotic
      retractions of the mesentery were observed. Fibrotic thickening of the peritoneum
      was found histologically in all animals. In spontaneous peritonitis in rats, we
      often found complicated clinical courses, catheter closure, intraperitoneal
      adhesion, and fibrotic thickening of the peritoneum.

PMID- 8534738
TI  - Absorption of iron dextran from the peritoneal cavity of rats.
AB  - We investigated the absorption rate and acute toxicities of intraperitoneal iron
      dextran in rats. Eighteen Sprague-Dawley rats were divided into three groups (n =
      6). The animals were given standard 1.5% Dianeal (group 1) or 1.5% Dianeal
      containing iron in a concentration of 2 mg/L (group 2) or 10 mg/L (group 3) as
      iron dextran. First, a predialysis blood sample was obtained, and 25 mL of the
      designated dialysis solution was instilled into the peritoneal cavity. After a 6
      hour cycle the dialysate was drained, and a postdialysis blood sample and
      specimen of the peritoneum were obtained. The iron concentrations of the dialysis
      solution, the dialysate, and both serum samples were determined. Histological
      samples were processed by hematoxylin and eosin and Prussian blue stain. Results
      of the iron concentration (mg/L) of the dialysis solution, the dialysate, and the
      percent of the absorbed iron were as follows: group 1: 0.00, 0.20 +/- 0.15, N/A;
      group 2: 2.24, 0.66 +/- 2.8, 73.8 +/- 11.0; group 3: 9.84, 2.12 +/- 0.62, 80.8 +/
      5.7. The serum iron concentration did not change. No abnormal findings were
      found histologically. More than 70% of the iron dextran was absorbed from the
      peritoneal cavity of the rats during a 6-hour peritoneal dialysis exchange.
      Intraperitoneal iron dextran may be an alternative route of iron delivery.

PMID- 8534739
TI  - Peritoneal transport in type I (insulin-dependent) and type II (noninsulin
      dependent) diabetic peritoneal dialysis patients.
AB  - Alterations in the fibrinolytic system have been demonstrated in noninsulin
      dependent diabetic patients (NIDDM) but not in insulin-dependent diabetic
      patients (IDDM). Since the activity of the fibrinolytic system can affect the
      turnover of extracellular matrix and therefore theoretically can affect the
      peritoneal transport, we tried to determine if there was a difference in the
      performance of the peritoneal equilibration test (PET) between IDDM and NIDDM
      patients receiving peritoneal dialysis (PD). The PET data from 11 IDDM patients
      (2 female, 9 male) and 13 NIDDM patients (3 female, 10 male) were reviewed. These
      two groups of patients were matched in gender, duration of end-stage renal
      disease, PD, and hypertension, blood pressure, degree of uremia, weekly KT/V, and
      body surface area. The IDDM patients (41.4 +/- 13.9 years) were younger than the
      NIDDM patients (58.8 +/- 7.1 years, p = 0.0026). There were no differences in
      hematocrit and serum chemistry profile including glucose and albumin between the
      two groups. Our data showed that there was no difference in PET performance
      between IDDM and NIDDM patients.

PMID- 8534740
TI  - Increased peritoneal solute transport in diabetic peritoneal dialysis patients.
AB  - Microangiopathy has been observed in the peritoneum of diabetic patients, and an
      increase in vascular permeability to small and large molecules has been described
      in the skeletal muscle of diabetic patients. Therefore, we examined the
      peritoneal equilibration test (PET) data from 19 diabetic and 19 nondiabetic
      stable peritoneal dialysis (PD) patients. These two groups of patients were
      matched in terms of age, gender, duration of PD and hypertension, incidence of
      peritonitis, levels of blood pressure, degree of uremia, levels of serum lipids,
      hematocrit, weekly KT/V, and body surface area. Compared to the nondiabetics, the
      diabetics had higher dialysate-to-serum ratios or mass transfer coefficients of
      urea or creatinine. These differences were not related to their differences in
      serum sodium or glucose. Regression analysis showed that the duration of
      hypertension was a negative determinant of peritoneal transport of urea and
      creatinine in diabetic patients. Our results suggest that the diabetic patients
      had a higher peritoneal diffusive transport of small solutes, which was offset by
      their duration of hypertension.

PMID- 8534741
TI  - Use of bethanechol chloride to increase available ultrafiltration in CAPD.
AB  - Reabsorption of peritoneal dialysis fluid during the prolonged dwell time of
      continuous ambulatory peritoneal dialysis (CAPD) reduces the efficiency of
      ultrafiltration and sacrifices effective dialysis adequacy. Studies by Nolph
      indicate a predominant role of lymphatics in this fluid loss. Khanna has reported
      that lymphatic flow may be influenced by acetylcholine. This study was designed
      to determine if bethanechol chloride (BC) would increase the availability of
      drained volume during CAPD. Nine patients were studied, including 7 patients who
      exhibited inadequate ultrafiltration. During a 5-day control period, total
      dialysate drained volume was collected and a standard peritoneal equilibration
      test (PET) performed. This was followed by a corresponding 5-day test period in
      which BC (mean dose 0.27 +/- 0.13 mg/kg/day) was administered orally. Drained
      volume during the control standard 4-hr PET was 1996.68 +/- 279.87 mL. The result
      for the test period was 2363.33 +/- 321.13 mL (p < 0.05), indicating an 18.4%
      increase using BC. The PET indicated no change in transport of urea, creatinine,
      and glucose. In conclusion, the total drained volume can be effectively increased
      with a subsequent increase in metabolite clearance using BC. Patients exhibiting
      inadequate ultrafiltration were able to be maintained on CAPD using this
      cholinergic drug.

PMID- 8534742
TI  - Effect of glucose on TGF-beta 1 expression in peritoneal mesothelial cells.
AB  - The peritoneum's response to peritoneal dialysis is a complex and poorly
      understood process that can result in fibrosis. The transforming growth factor
      beta(TGF-beta 1) plays a central role in regulating tissue repair and remodeling
      after injury. To determine the role of mesothelial cells during peritoneal
      dialysis in the alteration of the peritoneum, we studied the effect of glucose on
      TGF-beta 1 expression by mesothelial cells. Human mesothelial cells were cultured
      in serum-free DMEM with different glucose concentrations for 48 hours. TGF-beta 1
      messenger (mRNA) was measured by slot-blot hybridization using a TGF-beta 1 cDNA
      probe. The result was that glucose stimulates TGF-beta 1 mRNA expression in a
      dose-dependent way. The expression was more profound in high glucose
      concentrations. This suggests that TGF-beta 1 mRNA may overexpress by mesothelial
      cells due to the procedure of dialysis, which may be the most important mechanism
      of alteration of the peritoneum during peritoneal dialysis.

PMID- 8534743
TI  - Hypotension in CAPD: role of volume and sodium depletion.
AB  - The prevalence of hypotension in continuous ambulatory peritoneal dialysis (CAPD)
      patients varies between 10% and 16%. The main causes of hypotension in these
      patients include hypovolemia, antihypertensive medications, myocardial failure,
      and a variety of poorly understood causes, viz, severe autonomic neuropathy,
      amyloidosis, malignancies, adrenal insufficiency, removal of vasopressor
      substances by dialysis and steroid withdrawal. In addition, there are a large
      number of patients with hypotension due to unknown causes. Between 1989 and 1994
      we had 65 of 525 CAPD patients suffering from persistent hypotension. Sixteen
      (25%) patients were hypovolemic, 14 improved after increasing the target weight,
      but 2 did not because of concurrent administration of coronary vasodilators. The
      various steps in the treatment of this group include fluid repletion after
      discontinuing anti-hypertensive medications and excluding myocardial failure,
      oral sodium supplementation and possibly increasing the dialysate sodium.
      Preventive measures include frequent assessment of the hydration status.
      Judicious use of diuretics is also important. Bioelectrical impedance and
      inferior vena caval ultrasound are two promising tools to assess the fluid status
      and supplement careful clinical examination.

PMID- 8534744
TI  - Low sodium concentration solution in normohydrated CAPD patients.
AB  - The aim of this study was to examine the possibility of increasing sodium and
      water removal with peritoneal dialysis. Ten patients aged 67.3 +/- 6.2 years, on
      continuous ambulatory peritoneal dialysis (CAPD) for 28.1 +/- 13.9 months, with
      no episodes of peritonitis for at least 2 months and clinically normohydrated,
      gave their informed consent to undergo two consecutive peritoneal equilibration
      tests (PETs) with dialysis solution at a sodium concentration of 126 mEq/L (low
      sodium) and 132 mEq/L (normal sodium), both with 2.5% glucose. Net
      ultrafiltration and sodium mass transfer were 319.4 +/- 178.5 and 443.2 +/- 234.4
      mL (p = 0.0346) and 27.7 +/- 24.5 and 28.2 +/- 27.1 mEq (p = NS), respectively.
      There were no variations in natremia or the transport indices of the studied
      solutes or in the arterial pressure or heart rate. All patients showed drowsiness
      or torpor during the low sodium PET and one had cramps. The 126 mEq/L sodium
      dialysis solution showed no advantages compared to the more common solution, 132
      mEq/L. However, further study is necessary to check the potentiality of solutions
      with different sodium and glucose compositions for both acute and chronic use.

PMID- 8534745
TI  - Discrepancy between weekly KT/V and weekly creatinine clearance in patients on
      CAPD.
AB  - Currently, weekly KT/V and weekly creatinine clearance (WCC) are used to
      quantitate continuous ambulatory peritoneal dialysis (CAPD), the minimum
      recommended requirements being 1.7/week and 50 L/week, respectively. There is no
      substantial evidence that one index is better than the other, and there is no
      clear recommendation what one should do if there is a discrepancy between these
      two values. We performed a cross sectional analysis of 68 patients in whom we
      measured weekly KT/V, WCC, residual clearances, and a 4-hr peritoneal
      equilibration test (PET). The correlation between KT/V and WCC in the whole group
      was highly significant (p < 0.0001); when patients were divided in the four PET
      groups, there was a significant correlation (p < 0.05) in the low-average (n =
      22) and high-average (n = 21) PET groups, but the correlation was not significant
      in the high (n = 13) and low (n = 12) PET groups. Fourteen of 68 patients (20%)
      showed a discrepancy between KT/V and WCC: 7 patients had a KT/V < 1.7 and WCC >
      or = 50 (group 1), and 7 patients had a KT/V > or = 1.7 and WCC < 50 (group 2).
      Those in group 1 with a WCC > 50 had a higher residual renal function (0.82 vs
      0.11 mL/min, p < 0.05) than those in group 2 and therefore had a higher tubular
      secretion of creatinine and reabsorption of urea. Those in group 2 with a KT/V >
      1.7 had lower creatinine equilibration than those in group 1 (D/Pcr 0.56 vs 0.75,
      p < 0.05) and therefore a better removal of urea than creatinine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8534746
TI  - The method used for volume estimation significantly influences KprT/V results in
      peritoneal dialysis patients.
AB  - We studied 51 patients (age 50 +/- 15 years; weight 75 +/- 17 kg; blood urea
      nitrogen 62 +/- 20 mg/dL), 61% of whom were obese. The volume of distribution of
      urea was estimated by anthropometric formulas (Watson and Hume) and as 58% of
      actual and ideal body weight. Volumes derived from use of 58% of actual body
      weight were highest (43.4 +/- 10.0 kg; p = 0.0005); no differences were noted
      between Watson and Hume volumes and those obtained using 58% of ideal body weight
      (38.5 +/- 8.0, 39.4 +/- 7.5, and 37.0 +/- 5.6 kg, respectively). Normalized daily
      urea clearance (KprT/V) was lowest and highest when using 58% of actual and ideal
      body weight, respectively (0.251 +/- 0.081 and 0.290 +/- 0.091; p < 0.0001).
      KprT/V values derived using the Watson and Hume methods were similar (0.279 +/-
      0.081 and 0.274 +/- 0.083, respectively), but significantly lower than those
      obtained using actual body weight (p < 0.0001). Differences were magnified in
      obese patients. A subset of patients underwent hemodialysis for urea volume
      measurement by urea kinetic modeling. Volume estimates using bioelectrical
      impedance showed the least bias when compared to values calculated during a
      hemodialysis treatment. We conclude that KprT/V is very dependent on body habitus
      and the method used for volume determination. Standardization of the volume
      parameter is essential to defining therapeutic guidelines and for meaningful
      comparisons between centers.

PMID- 8534747
TI  - Variability in calculations of dialysis adequacy in patients using nightly
      intermittent peritoneal dialysis compared to CAPD.
AB  - Increasing numbers of patients receive peritoneal dialysis using noncontinuous
      methods such as nightly intermittent peritoneal dialysis (NIPD) rather than
      continuous ambulatory peritoneal dialysis (CAPD). We hypothesized that blood
      solute levels before and after NIPD would be large enough to produce significant
      variability in formulas based on the continuous peritoneal dialysis (PD) model.
      We found no diurnal differences in serum creatinine in NIPD or CAPD. However, our
      data demonstrate a 7.9% difference in serum urea measurements from evening to
      morning in patients treated by NIPD. This mathematical difference contributes to
      a 6.3% difference in the calculated value of KT/V and a 9.4% difference in the
      calculation of total urea clearance (liters per week) in these patients. By
      contrast, no difference in serum values or in calculated values of adequacy could
      be shown in patients on CAPD. These observations support the premise that CAPD
      represents a steady-state condition. NIPD patients demonstrate variability in
      serum levels of urea which may result in inaccurate calculations of dialysis
      adequacy. When blood samples are obtained in the morning soon after completing a
      cycle of NIPD, dialysis adequacy as measured by KT/V or total urea clearance (but
      not by total creatinine clearance) may be systematically overestimated.

PMID- 8534748
TI  - Effect of increasing exchange volume or frequency on CAPD efficiency.
AB  - We evaluated the effect of increasing the volume of all exchanges (group A),
      increasing exchange frequency (group B), or increasing nocturnal exchange volume
      alone (group C) on dialysis urea and creatinine clearances (DUrCl and DCrCl,
      respectively) and on KT/V in 20 continuous ambulatory peritoneal dialysis (CAPD)
      patients (25 maneuvers in 20 patients). The average duration of the maneuver was
      4.5 +/- 2.1 months. In group A, a significant increase occurred in DCrCl and
      DUrCl. Residual renal function (RRF) decreased by an average of 0.5 mL/min (not
      significant, NS). In group B, DUrCl increased by 19% (NS). RRF decreased
      significantly from 2.5 +/- 1.0 mL/min to 1.0 +/- 0.6 mL/min. In group C no
      changes were noted in dialysate clearances or RRF. In all groups KT/V was
      maintained regardless of the maneuver employed and despite the changes in
      dialysis clearance observed in groups A and B. This stability is probably related
      to the significant decline in RRF for the group as a whole during the observation
      period. KT/V can be maintained as RRF declines with either increases in dialysate
      volume or exchange frequency. However, efforts to increase KT/V to higher
      mandated values will probably require changes in both dialysate volume and
      frequency.

PMID- 8534749
TI  - The analysis of simple sequence repeat DNA in soybean by Capillary Gel
      Electrophoresis.
AB  - The objective of this work is to examine the presence of simple sequence repeat
      (SSR) DNA in soybean plant genotypes by Capillary Gel Electrophoresis (CGE). The
      SSR DNA length polymorphism in soybean determines the variation in polymerase
      chain reaction (PCR) product lengths. Loci were chosen where amplification
      produced one PCR product per genotype (M.S. Akkaya et al., 1992). The F1 hybrids
      of parents carrying different alleles produced two PCR products identical to the
      two parents. The CGE system used a 3%T,3%C polyacrylamide gel capillary with an
      effective length of 40 cm. The PCR products with lengths of 150 to 200 base pairs
      were monitored at 260 nm. The analysis time was under 50 minutes. CGE is capable
      of separating these PCR products by base pair number the same as conventional
      sequencing gel techniques. CGE offers an automated, high speed, high resolution
      analytical method for determining soybean SSR allele sizes as compared with the
      traditional methodologies.

PMID- 8534750
TI  - Altered protein synthesis in p53 null and hemizygous transgenic mouse embryonic
      fibroblasts.
AB  - Embryonic fibroblasts derived from p53-deficient transgenic mice showed distinct
      phenotypic and biological changes in vitro. In this study, we investigated the
      possible impact of p53 on the synthesis of other cellular proteins by comparing
      the protein profiles of p53 null (-/-), hemizygous (+/-) and p53 positive
      homozygous (+/+) cells using high resolution two dimensional gel electrophoresis.
      A total of more than 850 proteins were detected in each cell line labeled with
      35S-methionine by using computerized image analysis, and a number of proteins
      were detected with qualitative or quantitative changes in p53-/- cells and to a
      lesser extent in p53+/- cells. Specifically, seven proteins became undetectable,
      and no new proteins were detected in p53-/- cells. Neither newly expressed nor
      absent proteins were detected in p53+/- cell line. Quantitatively, a total of 97
      and 59 proteins were detected with significant quantitative changes (3 fold or
      greater) in p53-/- and p53+/- cells, respectively. Generally, most protein
      changes fell into one of the following four patterns: 1) progressively decreased
      synthesis in cells from p53+/+ to p53+/- to p53-/- cells; 2) progressively
      increased synthesis in cells from p53+/+ to p53+/- to p53-/- cells; 3) decreased
      synthesis only in p53-/- cells; and 4) increased synthesis only in p53-/- cells.
      A 70 kD heat shock protein (Hsp 70) was identified and showed a greater than
      1,000-fold increase in p53-/- cells compared to that in p53+/+ cells.
      Transferrin, tropomyosin, and proliferating cell nuclear antigen (PCNA) have also
      been identified and measured in this study. Synthesis of transferrin and
      tropomyosin was significantly increased or decreased, respectively in p53-/-
      cells, whereas expression of PCNA showed no significant change in p53-/- cells
      despite their much higher (3-4 times) proliferation rate than the other two cell
      lines (p53+/+ and p53+/- cells). We conclude that disruption of a single
      important gene, p53, results in a cascade of protein changes which are related to
      the loss of p53 mediated negative growth effects on cell cycle control.

PMID- 8534751
TI  - Recovery of SDS-protein and DNA using commercial automated gel electrophoresis
      apparatus.
AB  - The HPGE-1000 apparatus (LabIntelligence, Menlo Park, CA) is a gel
      electrophoresis instrument with intermittent fluorescence scanning of the
      migration path and with preparative capability. An electroelution cup sealed with
      gel is placed onto the band of interest, identified and located under computer
      control, and the band is electroeluted into the cup at a right angle to the
      orientation of the resolving gel. The correct location of the eluted band and the
      degree of its recovery into the elution cup are then verified on the gel pattern,
      visualized on the computer screen. Using that procedure, SDS-conalbumin-FLUOS was
      electrophoresed at 5 V/cm in a discontinuous tricinate-chloride-Tris system at
      loads of 0.25 to 20 micrograms, using 5% agarose (MetaPhor, FMC), 0.03% SDS gel
      at 5 degrees C. The horizontal gel was partitioned at the sample loading slit
      between a gel in Tris-tricinate (prepared at the concentrations of an operative
      phase ZETA) and in Tris-chloride (prepared as phase BETA). The elution cup was
      sealed with the latter gel and overlayered with buffer of the composition of the
      former. This arrangement should provide for electroelution of the band as a
      highly concentrated stack. At electroelution times of 2, 3.5, 4-5, 12, 15 and 15
      min at 15 V/cm yields were 58, 60, 54-76, 99, 99 and 84% for loads of 0.25, 0.5,
      1, 4, 10 and 20 micrograms, respectively. At the most sensitive scale of
      detection (13), a full-scale peak was obtained at a load of 1.7 micrograms when
      the fluorophore (FLUOS, Boehringer-Mannheim) to protein ratio was 10:1.
      Similarly, homogeneous nucleosomal DNA (146 bp), electrophoresed in 0.2 x TBE
      buffer at a load of 5 micrograms, was near-quantitatively recovered into the same
      buffer by electroelution at 15 V/cm for 2.5 or 6 min.

PMID- 8534752
TI  - A computer program for predicting recovery of SDS-protein in the automated HPGE
      1000 apparatus.
AB  - The commercial automated gel electrophoresis apparatus (HPGE-1000 of
      LabIntelligence, Menlo Park, CA) allows one to recover the material migrating and
      visualized as a fluorescent-labeled band by electrophoresis into a collection cup
      located above the band at a right angle to the orientation of the separation
      path. The degree of recovery is a function of sample load (peak area),
      electrophoresis time at constant field strength, the mobility of the material and
      band width. Neglecting the latter, recovery of several SDS-proteins was measured
      as a function of the first three parameters. These measurements were used as a
      data base for a computer program capable of predicting, by interpolation of the
      experimental values, the time of electrophoresis needed to obtain a specified
      degree of recovery, or the degree of recovery obtained after a desired time of
      electrophoresis into the collection cup.

PMID- 8534753
TI  - Human lymphocyte cDNA ordered library analyzed by 2D gel electrophoresis. 1.
      Pooling strategy and matching of gel patterns.
AB  - We have analyzed an ordered library of 4,608 cDNA clones from the CEM human
      leukemic cell line. The aim was to facilitate gene retrieval, to enable immediate
      access to cDNA clones and to provide information on the protein expression of the
      individual clones in a 2D gel readout. The matrix array of 24 x 16 x 12, each
      position of which contained lambda jacII phage from one plaque, enabled us to
      establish pools of clones along the three axes (24 pools of complexity 192 cloned
      entities, 16 pools of complexity 288 and 12 pools of complexity 384). The total
      cDNA complexity is here reduced to such a level that spots which in more complex
      gels served as landmark spots are not present in each pool, and thus cannot serve
      as landmarks anymore. The image analysis of such gels and especially the matching
      of spots is not reliable under these circumstances. In order to achieve reliable
      matching, additional samples were created, such that pools were co
      electrophoresed according to a special concatenation scheme; these samples then
      contained over-lapping elements (e.g., pools 1 + 2 + 3 and 3 + 4 + 5 have at
      least those spots in common, which originate from pool 3). This approach turned
      out to be feasible and we have completed the matching of one half of the ordered
      library. Already from the present stage of analysis we have obtained valuable
      information on the cDNA library and on the distribution of clones in this
      library.

PMID- 8534754
TI  - Human lymphocyte cDNA ordered library analyzed by 2D gel electrophoresis. 2.
      Frequency distribution of mRNA populations.
AB  - Cell-free transcription and translation products from an ordered library of cDNA
      clones from the CEM human leukemic cell line were submitted to analysis using two
      dimensional gel electrophoresis as a read out system. The matrix array of 24 x 16
      x 12 wells contained in each of the positions lambda jacII phages from one
      plaque. Pools of clones along the three axes (24 x-pools, 16 y-pools and 12 z
      pools) were established. Results obtained upon matching of 12 x-pools were
      scrutinized for estimating the frequency of cDNA molecular species in the
      library. The results obtained are interpreted in such a way that there are no
      discrete distributions of mRNA molecular species, but rather there is a
      continuous distribution of mRNA's covering a wide range of frequencies. The
      lowest frequency found was about 4.5 x 10(-4) and the highest 1.6 x 10(-2). About
      half of all clones can be found among these low frequency ones (each occurring
      0.45 times among 1,000 clones).

PMID- 8534755
TI  - An improved strategy for HLA-DRB1 subtyping by digestion of PCR-amplified DNA
      with allele-specific restriction endonucleases.
AB  - We developed a simple, rapid and inexpensive method of DRB1 alleles genotyping by
      digestion of amplified DNA with allele-specific restriction fragments
      endonucleases. We took advantage of this protocol, initially described by Yunis
      et al. (1991) and called AFLP (Amplification Length Fragment Polymorphism) to
      standardise amplification procedure. Typing strategy was particularly studied to
      limit the number of restriction endonucleases. The determination of DRB1 allele
      was established on lysed fragments size which allows: (1) the absence of
      nonidentified allele and (2) a nonambiguous determination of each heterozygous
      allele. Six specific pairs of primers were chosen to amplify three generic
      groups: HLA DR 124 (DRB1 1, 2 and 4), HLA DR356810 (DRB1 3, 5, 6, 8 and 10) and
      DR79 (DRB1 7 and 9) with the same PCR protocol. Forty-eight from the 60 DRB1
      alleles may be identified without any ambiguity. With our protocol, the three
      alleles associated with the most important autoimmune diseases (i.e., DRB1*02,
      *03 and *04) were totally subtyped. Our amplification procedure is reliable and
      extremely useful in routine-practice for the study of HLA-DRB1 genotyping of
      large series of samples and for the determination of DRB1 susceptibility factors
      involved in different autoimmune diseases.

PMID- 8534757
TI  - Levels of the terminal complement complex, C3a-desArg and C1-inhibitor in adult
      patients with capillary leak syndrome following bone marrow transplantation.
AB  - Capillary leak syndrome (CLS) is a severe complication after bone marrow
      transplantation (BMT). To investigate whether there is a pathogenetic role of the
      complement system, we monitored the levels of the terminal complement complex C5b
      9 (TCC) and C3a-desArg as indicators of an activation of the complement system
      and the inhibitor of the classical pathway of the complement cascade, C1
      inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to
      5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48
      patients between days 1 and 12 after BMT. Complement activation as indicated by
      TCC levels was more pronounced in patients with CLS (n = 7) from day -8 to +28 (p
      < 0.05; day -1) and the elevation of TCC levels lasted longer in CLS patients
      (peak day 21) than in patients without this complication (peak day 7). Mean C3a
      desArg levels were highest in patients with CLS reaching a peak at day 7. During
      the early posttransplant period a significant elevation of C1-INH levels (p <
      0.01 and p < 0.05 respectively) compared with baseline levels (day -8) was found
      in patients with and without CLS, which was more pronounced in those patients
      with CLS (p < 0.05). Although we could not observe an absolute C1-INH deficiency
      as compared to healthy individuals our data support the presence of a relative
      deficiency of the inhibitor which might explain the reported beneficial effects
      of C1-INH substitution in BMT related CLS.

PMID- 8534756
TI  - Clinical application of allogeneic peripheral blood stem cells transplantation.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF)-mobilized
      peripheral blood stem cells (PBSC) are now widely used for autologous
      transplantation to provide hematopoietic stem cells after intensive
      chemoradiotherapy. However, PBSC which contain a large number of T cells
      represent a potential risk for graft-versus-host disease (GVHD) in allogeneic
      (allo) transplantation. There are about 50 case reports of clinical trials of rhG
      CSF-mobilized allo PBSC transplantation (PBSCT) with relatively rapid
      hematological recovery, without severe acute GVHD except in a few cases.
      Therefore, the risk of inducing severe acute GVHD is not as high as was expected
      when allo PBSCT began. However, whether allo PBSCT will increase the risk of
      chronic GVHD is not clear, because the period of observation has been too short.
      Also, it will be of interest to determine the clinical effect of allo PBSCT on
      relapse of hematological malignancy post-transplant. Whether allo PBSCT will
      increase life-threatening acute and chronic GVHD, and whether PBSC allografting
      will result in permanent hematological and immunological reconstitution has to be
      determined by prospective randomized clinical trials.

PMID- 8534758
TI  - Changes of nucleolar organizer regions in granulopoietic precursors during the
      course of chronic myeloid leukemia.
AB  - The aim of the present study was to analyze the nucleolar organizer region
      (AgNOR) pattern of granulopoietic precursors in chronic myeloid leukemia (CML) at
      diagnosis and during the course of the disease. Clusters of AgNORs and isolated
      dots were counted separately in 24 cases of CML at diagnosis, in 19 cases during
      the relapse of the chronic phase after treatment, and in 16 cases of blast
      crisis. For comparison, 20 cases of normal bone marrow were studied. Each cell
      type had its own characteristic AgNOR pattern, as has been described for normal
      bone marrow. There was no significant difference in the number of AgNORs between
      cells in the peripheral blood and bone marrow. Compared with normal
      granulopoiesis, myeloblasts in CML at diagnosis had lower numbers of clusters,
      which decreased further during relapse of chronic phase and in blast crisis.
      Promyelocytes and myelocytes showed significantly fewer dots. The number of AgNOR
      clusters correlates inversely with the duration of the cell cycle. Therefore,
      these findings are consistent with the progressive loss in proliferative activity
      of immature precursors described during the course of CML. As the number of dots
      indicates cellular maturation, their lower number in promyelocytes and myelocytes
      in CML favors the concept of a discordant maturation process described in this
      disease. The separate counting of clusters and dots provides a useful, simple,
      and cheap method of describing cytokinetic changes during the course of this
      myeloproliferative disorder.

PMID- 8534759
TI  - Overproduction of inhibitory hematopoietic cytokines by lipopolysaccharide
      activated peripheral blood mononuclear cells in patients with aplastic anemia.
AB  - The aim of this study was to measure the level of cytokines produced by
      peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA)
      and to determine their effect on the clonal growth of normal bone marrow (BM)
      cells. Twenty-one patients with AA and 11 normal controls were enrolled in this
      study. Medium conditioned by PBMNC of AA patients in the presence of
      lipopolysaccharide (LPS) was found to be suppressive to the colony growth of
      normal BM cells. Thus, we further determined the presence in the PBMNC
      conditioned medium (CM) of both inhibitory cytokines: macrophage inflammatory
      protein-1 alpha (MIP-1 alpha), tumor necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta 2 (TGF-beta 2), and interferon-gamma (IFN-gamma),
      and stimulatory cytokines: interleukin-3 (IL-3) and stem cell factor (SCF).
      Spontaneous production of MIP-1 alpha was higher in the AA patients than the
      normal controls (1887 +/- 174 pg/ml vs 1643 +/- 93 pg/ml), but the difference was
      not significant. After LPS stimulation, the production of MIP-1 alpha was
      markedly increased in the AA patients, and its level was significantly higher
      than that of the normal controls (2360 +/- 149 pg/ml vs 1517 +/- 92 pg/ml, p =
      0.0022). The level of TNF alpha was also higher in the AA patients. However, IFN
      gamma, TGF-beta 2, SCF, and IL-3 were not detectable in the PBMNC-CM of either AA
      patients or normals. The myelopoietic suppressing effect of AA-PBMNC-CM from each
      AA patient was significantly blocked by pretreatment with anti-TNF-alpha,
      resulting in a colony-forming enhancement of 174% +/- 12%. A similar effect was
      noted in six of 11 AA patients by pretreatment with anti-MIP-1 alpha. We conclude
      that TNF alpha and MIP-1 alpha can be overproduced by the PBMNC of some AA
      patients, which may play a role in the progression of AA.

PMID- 8534760
TI  - Aerosol amphotericin B inhalations for prevention of invasive pulmonary
      aspergillosis in neutropenic cancer patients.
AB  - To determine the value of aerosol amphotericin B inhalations for prevention of
      invasive pulmonary aspergillosis (IPA), we initiated a prospective randomized
      multicenter trial. The scheduled intent-to-treat interim analysis included 115
      patients (30%) with prolonged neutropenia after chemotherapy for acute myeloid
      leukemia, acute lymphoblastic leukemia/high-grade non-Hodgkin's lymphoma, or
      solid tumors undergoing autologous stem cell transplantation. Sixty-five patients
      had been randomized to receive prophylactic aerosol amphotericin B inhalations at
      a dose of 10 mg twice daily (group A); for the remaining 50 patients no aerosol
      amphotericin B prophylaxis was used (group B). No serious side effects from
      amphotericin B inhalations occurred, but coughing (54%), bad taste (51%), and
      nausea (37%) caused early cessation of aerosol amphotericin B prophylaxis in 23%
      (15/65) of courses. In group A, the incidence of proven, probably, or possible
      IPA was 5% (3/65) as compared with 12% (6/50) in group B (p > 0.05).
      Microbiologically documented bacterial pneumonias were observed in 5/65 (8%)
      patients in group A and in 1/50 (2%) patients in group B (p > 0.05). Thus, no
      reduction in incidence of IPA from use of prophylactic aerosol amphotericin B
      inhalations was found in this interim analysis. As there were no serious side
      effects from aerosol amphotericin B prophylaxis, accrual in the study will
      continue for a total of 380 patients.

PMID- 8534761
TI  - Analysis of bone marrow and peripheral blood immunoregulatory lymphocytes in
      patients with myelodysplastic syndrome.
AB  - The cell surface phenotype of immunoregulatory lymphocytes in bone marrow (BM)
      and peripheral blood (PB) in myelodysplastic syndrome (MDS), a stem cell
      disorder, was analyzed. Mononuclear cells from 25 patients with refractory anemia
      (RA) and nine with RA with an excess of blasts (RAEB) were characterized by two
      color flow cytometry using various monoclonal antibodies. No significant change
      of CD3+, CD4+, and CD8+ cells in PB, but a decrease of the percent of positive
      cells for CD8++ among the total lymphocyte (%CD8++) was noticed in RA patients.
      On the other hand, in BM of RA patients, a decrease in the number of CD4+ cells,
      but not CD8++ cells, was noted. In RAEB patients, the absolute numbers of CD3+,
      CD4+, CD8+, and CD8++ cells in BM were decreased; however, the ratio of these
      lymphocytes was not changed. No change was observed among the CD4+ subsets in PB
      of RA or RAEB patients. In BM, a decrease in percentage of CD4+CD45RA+
      (%CD4+CD45RA+; naive cell) and increases in CD4+CD45RO+ (%CD4+CD45RO+; memory
      cell) and CD4+CD29+ (%CD4+CD29+; helper/inducer) among CD4+ cells were found in
      both RA and RAEB patients. Analysis of the CD8++ subset showed an increased
      number of CD8++CD11a+ cells (activated CTL) in both BM and PB of RA patients, but
      not of RAEB patients. Furthermore, increments in CD56+ and CD16+ cells among CD3-
      cells (natural killer; NK cells) were seen in RA patients but not in RAEB
      patients. It remains unclear whether lymphocytes in MDS patients were involved in
      the abnormal (MDS) clones, but our results regarding the increments of
      CD8++CD11a+ and NK cells in RA patients suggest that the mechanism of immune
      surveillance against the abnormal MDS clones was activated in these RA patients,
      but not in RAEB patients. Further investigation is required to clarify the
      functions of these immunoregulatory lymphocytes in MDS patients.

PMID- 8534762
TI  - Enhancing and suppressive effects of immunosuppressants cyclosporin A, FK506, and
      KM2210 on the colony formation of murine bone marrow cells.
AB  - Immunosuppressants cyclosporin A (CsA), FK506, and KM2210 modulated colony
      formations of murine hematopoietic progenitor cells. In a 4-h treatment with CsA,
      10 micrograms/ml increased the formation of colony-forming units of mixed
      lineages (CFU-Mix) but decreased the formation of highly proliferative potential
      colony-forming units (CFU-HPP); 1 microgram/ml of CsA increased the formations of
      CFU-HPP, CFU-Mix, and colony-forming units of granulocytes/macrophages (CFU-GM);
      0.1 microgram of CsA increased the formation of CFU-Mix and burst-forming units
      of erythroid lineage (BFU-E). Lower doses of CsA appeared to induce an increase
      in various colony formations. FK506 increased CFU-HPP and CFU-Mix formations at
      lower doses. Another immunosuppressant, KM2210, increased CFU-HPP and CFU-GM
      formations but decreased CFU-Mix and BFU-E formations. In a 24-h treatment, 10
      micrograms/ml and 1 microgram/ml of CsA inhibited all the colony formations, but
      0.1 microgram/ml of CsA increased CFU-Mix, CFU-GM, and BFU-E formations.
      Similarly, 100 ng/ml and 10 ng/ml of FK506 decreased all the colony formations
      but 1 ng/ml of FK506 increased CFU-HPP and CFU-GM formations. KM2210 inhibited
      all the colony formations. These findings showed that lower doses of CsA and
      FK506 appeared to increase the colony formations, although higher doses of these
      drugs decreased the colony formations, similar to the findings in a 4-h
      treatment. On the other hand, KM2210 showed opposing effects on colony formation
      with 4-h and 24-h treatments.

PMID- 8534763
TI  - Aggressive course of primary plasma cell leukemia with unusual morphological and
      cytogenetic features.
AB  - A case of aggressive plasma cell leukemia with unusual morphological and
      cytogenetic features is reported. A 65-year-old man was admitted to hospital due
      to anemia, thrombocytopenia, and renal insufficiency. Bone marrow examination and
      peripheral blood smear revealed a large number of pleomorphic cells with
      convoluted and multilobulated nuclei. Immunohistochemistry of the bone marrow
      biopsy was negative for anti-keratin antibodies CAM.5.2 and AE1/AE3, but positive
      for EMA. The immunophenotypic features of these cells were suggestive of plasma
      cell origin with positivity for CD38, CD56, CD9, and CD44 and a weak positivity
      for CD71 and CD45 (40% of the cells), while all other markers of hematopoietic
      origin were negative. Furthermore, a serum protein electrophoresis showed a
      monoclonal component type IgG-kappa of 70 g/l. The cytogenetic analysis
      demonstrated a hypotetraploid clone with multiple numerical and structural
      abnormalities. Although some of the aberrations found are associated with plasma
      cell malignancies--e.g., structural rearrangement of chromosome 1, del(6q), and
      monosomy 13--the karyotypic complexity in the present case is unusual. The course
      of the disease was very aggressive, and the patient died 3 days after admission.

PMID- 8534764
TI  - Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment
      of adult ALL.
AB  - In four of 14 patients with acute lymphoblastic leukemia (ALL) who received
      induction chemotherapy containing weekly injections of vincristine and
      simultaneous antifungal prophylaxis with itraconazole, unusually severe and early
      vincristine-induced neurotoxicity was observed. In these patients (three female,
      one male) paresthesia and muscle weakness of the upper/lower extremities and
      paralytic ileus occurred after the first or second vincristine injection. In one
      patient a laryngeal nerve paresis required mechanical ventilation. The neurotoxic
      complications were more serious than those seen in a previous series of 460 ALL
      patients under the identical cytostatic regimen but without itraconazole
      prophylaxis. The underlying mechanism is unclear. Interaction with the cytochrome
      P-450 system, reversal of multidrug resistance, and influence of estrogens are to
      be considered.

PMID- 8534765
TI  - Hypereosinophilic syndrome in Hodgkin's disease with increased granulocyte
      macrophage colony-stimulating factor.
AB  - We report a patient with eosinophilia accompanied by Hodgkin's disease who showed
      remarkable increase in granulocyte-macrophage colony-stimulating factor (GM-CSF)
      in plasma but no increase in interleukin-5 (IL-5). The plasma GM-CSF level
      normalized as eosinophilia and lymphadenopathy disappeared after chemotherapy.
      Immunohistochemical study with immunoperoxidase staining technique showed a
      positive stain in lymph node cells by monoclonal anti-GM-CSF antibody.
      Eosinophilia is often accompanied by Hodgkin's disease, and several cases have
      been reported to show high levels of plasma IL-5. To our knowledge, this is the
      first report to show a high level of plasma GM-CSF in Hodgkin's disease with
      eosinophilia.

PMID- 8534766
TI  - A case of eosinophil peroxidase deficiency.
AB  - A case of eosinophil peroxidase deficiency is described after fortuitous
      detection by the H*3 Technicon hematological analyzer. From the cytochemical
      aspect total deficiency is admitted. The abnormality is thought to be extremely
      rare in a well-mixed population as exists in the Grand-Duchy of Luxembourg.

PMID- 8534767
TI  - Correlation between immunophenotypic diversity and clinical features in B-cell
      lymphoblastic lymphoma.
AB  - Lymphoblastic lymphoma (LBL) is a highly malignant subtype of non-Hodgkin's
      lymphoma (NHL) and generally carries a T-cell phenotype with mediastinum or
      central nervous system (CNS) involvement. However, only a small proportion of LBL
      exhibit a B-cell phenotype (B-LBL), and these frequently present at the head and
      neck without mediastinum or CNS involvement. Three immunological subgroups may
      exist. The most predominant CD10-positive pre-B-cell type, corresponding to a
      precursor B-cell neoplasm, frequently involves the head and neck. The second,
      CD10-negative or mature B-cell type, defined by the absence of CD10 or presence
      of surface membrane immunoglobulins combined with expression of CD19 or CD20,
      often involves the mediastinum. The final group is a CD5-positive B-cell type
      corresponding to a blastic variant of mantle cell lymphoma (MCL). Its clinical
      course is less aggressive, patients are often older, and nodal lesions are more
      frequent than extranodal involvement. Thus, B-LBL is immunologically diverse, but
      its biological behavior correlates with the immunophenotype.

PMID- 8534768
TI  - Relationship between serum unconjugated bilirubin levels and the autofluorescence
      of white blood cells in neonatal jaundice.
AB  - In this study, using flow cytometry, we investigated the autofluorescence emitted
      by lymphocytes, monocytes and neutrophils exposed to different unconjugated
      bilirubin concentrations and investigated the relationship between these
      parameters. Different unconjugated bilirubin concentrations were prepared from a
      newborn serum with an unconjugated bilirubin concentration of 800 m mumol/l. The
      same concentrations of unconjugated bilirubin have been prepared from pure
      bilirubin. 10 microliters of cord blood were incubated at room temperature for 15
      min with 90-microliter solutions with different bilirubin concentrations prepared
      from both serum and pure bilirubin. After incubation, cells were washed three
      times with PBS, erythrocytes were lysed by lysing buffer and run through flow
      cytometry immediately. Autofluorescence was measured by recording mean
      fluorescence channels for lymphocytes, monocytes and neutrophils. There was a
      good correlation between serum concentrations of unconjugated bilirubin that
      cells were exposed to and the autofluorescence intensity of neutrophils (r =
      0.904, p < 0.005), monocytes (r = 0.759, p < 0.05) and lymphocytes (r = 0.766, p
      < 0.01). Results obtained with pure bilirubin were also similar. Autofluorescence
      emitted by lymphocytes was lower than that of monocytes (p < 0.01) or neutrophils
      (p < 0.0005).

PMID- 8534769
TI  - Maternal and neonatal plasma cytokine levels in relation to mode of delivery.
AB  - After birth, host defences must be recruited to manage the transition from an
      almost sterile to a normal environment. The present study was undertaken to
      evaluate the relationship between cytokine plasma levels and phagocyte burst in
      mothers and neonates during the peripartal period. Plasma levels of interleukin
      (IL)-1, IL-6, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and whole blood
      superoxide anion (.O2-) generation were evaluated in 27 healthy mothers, 16
      undergoing vaginal delivery (VD) and 11 elective caesarean section (ECS) and in
      their babies. Blood specimens were taken from the mothers at the beginning of
      labour, during labour, immediately after delivery and 4 days later in the VD
      group, and before anaesthesia, immediately after delivery and 4 days later in the
      ECS group; neonatal samples were taken at birth (cord blood) and 4 days later.
      After delivery by VD, these mothers had higher plasma levels of IL-1 beta, IL-6,
      IFN-gamma and higher .O2- generation than those delivered by ECS. IL-6 plasma
      levels and .O2- generation were higher in babies born by VD than in those born by
      ECS. A statistically significant correlation between IL-6 plasma levels and .O2-
      release was observed in cord blood of babies born by VD (r = 0.69; p < 0.006).
      The study demonstrates that labour plays an important role in modulating host
      defences in the newborn.

PMID- 8534770
TI  - Ontogeny of rat myocardial A1 adenosine receptors.
AB  - Adenosine functions as a counterregulatory hormone in the myocardium by
      decreasing work and thereby protecting the myocardium against ischemia.
      Functional adenosine A1 receptors could serve as an important regulatory system
      in the developing preinnervated heart by balancing the humoral sympathetic input
      to the heart. The aims of this study were to determine if A1 adenosine receptors
      were functionally coupled to their Gi protein in the immature preinnervated heart
      and to determine if A1 adenosine receptors were present in greater numbers in the
      immature heart. One- to 3-day-old rat ventricular cardiomyocyte cultures were
      exposed to (1) control conditions; (2) isoproterenol, a beta-receptor agonist,
      (3) R-PIA, an A1 agonist, or (4) isoproterenol and R-PIA, cAMP levels were
      determined by RIA in each group. Adenosine A1 receptor density and the
      equilibrium dissociation constant were determined by binding of an adenosine A1
      receptor antagonist in newborn, 1-week-old, 2-week-old, and adult rat hearts. A1
      stimulation decreased the isoproterenol-induced increase in cAMP by 30%,
      demonstrating functional A1 receptors in immature preinnervated myocytes. The A1
      receptor density in the newborn age group was twice the adult and 2-week-old
      level. We conclude that A1 receptors in the immature heart are functionally
      coupled to their effector and that A1 receptors are present in greater numbers in
      the immature heart.

PMID- 8534771
TI  - Lipoprotein lipase activity in developing rat brain areas.
AB  - Lipoprotein lipase (LPL) is a key extracellular enzyme that enables tissue to
      import fatty acids from triacylglyceride-rich lipoproteins. LPL is present in
      most tissues of the body, but in the brain its functional significance remains
      unclear. Lipids constitute the main components of myelin and undergo significant
      changes during maturation. However, nothing is known of the postnatal evolution
      of LPL activity in the brain areas during postnatal development. Here we found
      that LPL activity is relatively high in the newborn brain and peaks between the
      5th and the 10th days after birth, reaching activities 5 times higher than in the
      adult brain. In all the areas studied (olfactory bulbs, cortex, thalamus,
      cerebellum, hippocampus, striatum, brain-stem and spinal cord) LPL also increases
      sharply during postnatal development. Hippocampus shows the highest LPL activity
      levels, which are between 5 and 11 times higher than in the other regions. The
      significance of these high LPL activity levels is discussed.

PMID- 8534772
TI  - Gene expression of fatty acid synthesizing enzymes in fetal rat lung in prolonged
      pregnancy.
AB  - In fetal lung the amounts of mRNAs encoding fatty acid synthase (FAS), acetyl-CoA
      carboxylase (ACC) and ATP citrate lyase (ACL) increase in late gestation and drop
      around birth. To study the mechanism of the perinatal decrease, pregnancy was
      prolonged from 22 (term) to 25 days in rats with daily injections of
      progesterone. Progesterone did not affect the levels of lipogenic enzyme mRNAs in
      fetal lung prior to term, but significantly delayed the perinatal decrease in the
      levels of lung FAS and ACC mRNA. Although for ACL mRNA abundance the differences
      were not statistically significant, its pattern in the control and progesterone
      groups were similar to those of FAS and ACC mRNA. Malic enzyme mRNA did not
      change between 20 and 25 days after conception in either group. These results
      suggest that the decrease in FAS and ACC mRNA at term can be partially explained
      by labor, delivery, air-breathing or switch from carbohydrate to fat metabolism.

PMID- 8534773
TI  - Rates of bilirubin clearance from rat brain regions.
AB  - The mechanism for the preferential distribution of bilirubin to basal ganglia
      ('kernicterus') is unknown. We hypothesized that differences in bilirubin
      clearance rates between brain regions might explain this phenomenon. Bilirubin
      [30 mg/kg over 5 min, with 370-740 kBq (10-20 mu Ci) tritiated bilirubin] was
      infused into a peripheral vein in unanesthetized, young Sprague-Dawley rats
      (n=36, weight 149 +/- 15 g, mean +/- SD). After blood sampling, groups of rats
      were killed at 15, 30, 45, 60, 75, 180, and 360 min with an intravenous injection
      of pentobarbital. Brain vasculature was flushed in situ and brains dissected into
      seven regions, which were weighed, dissolved and scintillation counted. Blood was
      analyzed for bilirubin, albumin, and blood gases. Brain bilirubin concentrations
      were calculated after determining the specific activity of bilirubin in serum at
      the time of sacrifice. Bilirubin half-lives in serum and brain regions were (in
      minutes, mean +/- SD): serum 24.6 +/- 17.2, whole brain 18.5 +/- 21.5, cortex
      17.6 +/- 19.3, hippocampus 19.0 +/- 21.5, striatum 17.1 +/- 18.5, midbrain 16.3
      +/- 18.6, hypothalamus 17.4 +/- 21.0, cerebellum 21.6 +/- 33.8, medulla 20.0 +/-
      24.1. There were no significant differences in bilirubin half-lives between
      regions. The half-life of bilirubin in brain reported here is appreciably shorter
      than the 1.7 h previously found in rats with opened blood-brain barriers, but
      appears compatible with data on auditory brainstem response reversibility
      following exchange transfusion in jaundiced infants. We conclude that bilirubin
      disappeares rapidly from brains with intact blood-brain carriers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8534774
TI  - Biochemical and morphological changes in the developing kidney.
AB  - We have studied microsomal phospholipid, cholesterol and protein concentration in
      rat renal papilla, medulla and cortex during postnatal development, and the
      relationship between these membranes biochemical parameters and morphological
      changes. We also determined DNA concentration in each kidney zone. No changes
      were observed either in papillary microsomal phospholipids, proteins and
      cholesterol or in DNA concentration from 10-to 70-day-old rats. Medullary
      microsomal proteins and cholesterol did not change but a significant increase was
      observed in the microsomal phospholipid concentration during development; in this
      case, medullary DNA was significantly lower at 70 than at 10 days. In contrast,
      all biochemical parameters in renal cortex were significantly higher during
      development except for DNA concentration which suffered a great decrease. These
      biochemical findings demonstrate that the developmental pattern is different in
      each zone of the kidney and confirm the fact that the papilla, in newborn rats,
      is almost fully developed whereas the renal cortex and medulla are immature.

PMID- 8534775
TI  - Intrathecal immune response in neonatal Flavobacterium meningosepticum
      meningitis.
AB  - Neonates are predisposed to serious infections such as meningitis, probably due
      to their immature host reaction to the pathogens. We have studied the intrathecal
      immune response in 2 newborns with Flavobacterium meningosepticum meningitis.
      They showed a significant elevation of immunoglobulin indices ( >1.10), also
      after the CSF had become sterile with a normalized cell count. In addition, an
      intrathecal increase and subsequent decrease of both C3dg and TCC (terminal
      complement complex) were observed in 1 patient. We conclude that immunoglobulin
      production and complement activation may occur in neonatal CSF.

PMID- 8534776
TI  - Somatostatin in preterm infants: postnatal changes and response to stress.
AB  - To determine the chronology of postnatal somatostatin (SRIF) changes in preterm
      infants and the relationship of SRIF levels to respiratory and gastrointestinal
      complications, we evaluated sequential SRIF levels in 62 preterm infants in the
      first month of life. Weekly preprandial plasma samples were obtained and analyzed
      for SRIF using a radioimmunoassay. Additional blood samples were obtained at the
      time of abdominal events. Somatostatin levels were highest in week 2 and
      gradually declined in weeks 3 and 4 (mean +/- SD pmol/l, SRIF = 92.3 +/- 30.3 in
      week 2 vs. 79.8 +/- 33.9 in week 3 and 69.7 +/- 54.4 in week 4, p < 0.03). Birth
      weight, gestational age and sex were not related to initial SRIF levels. Infants
      with respiratory distress requiring assisted ventilation had significantly higher
      week 1 SRIF levels compared to infants without respiratory problems (97.9 +/-
      22.7 vs. 74.9 +/- 21 pmol/l, p < 0.02). Twenty-one of the 62 infants had
      gastrointestinal complications. Somatostatin levels preceding (89.0 +/- 25.9
      pmol/ 1), during (91.0 +/- 13.3) and after (79.3 +/- 28.6) the gastrointestinal
      events were not significantly different, nor were they different from SRIF
      concentrations of age-matched preterm infants without gastrointestinal
      complications. The results suggest that in preterm infants, postnatal SRIF
      changes follow a definite pattern with peak concentrations in week 2. Respiratory
      distress is associated with a significant increase in SRIF. However, subsequent
      gastrointestinal events do not lead to an increase in SRIF. This lack of SRIF
      response in gastrointestinal stress may play a role in the pathogenesis of gut
      injury in the premature neonate.

PMID- 8534777
TI  - Gastroesophageal reflux and acute life-threatening episodes: role of a central
      respiratory depression.
AB  - The aim of this study was to evaluate plasma levels of beta-endorphins in babies
      with gastroesophageal reflux (GOR) admitted for acute life-threatening episodes
      (ALTE). In case of ALTE (n = 15), beta-endorphin levels were significantly
      increased compared to sudden infant deaths syndrome siblings with GOR of a
      similar gravity evaluated for risk factors (n = 13). beta-Endorphin levels are
      decreased following successful treatment of GOR. Studies of ventilation suggest
      that changes in the central respiratory drive are associated with a reduction in
      plasma beta-endorphin levels.

PMID- 8534778
TI  - Acute effects of indomethacin on cerebral hemodynamics and oxygenation.
AB  - Although an indomethacin-induced decrease of brain perfusion in preterm infants
      has been well established, the acute effects of this vasoactive drug on cerebral
      hemodynamics and oxygenation are not well documented. Using near infrared
      spectroscopy we monitored in 6 very preterm infants changes in cerebral blood
      volume (delta CBV) and cytochrome oxidase concentration (delta Cytaa3), used as
      relative measures of changes in brain perfusion and as an indicator for cellular
      oxygenation of brain tissue, during and up to 1 h after indomethacin infusion.
      delta CBV showed a quick blood-pressure-related increase as compared to baseline
      (preindomethacin values) during indomethacin infusion (averaged maximal increase
      13%), followed by a sharp decrease below baseline values (averaged maximal
      decrease 24%). There was a sustained recovery to baseline during the registration
      period. delta Cytaa3 showed a small, early increase in 4 of 6 babies, followed by
      a substantial decrease below baseline in 5 babies. delta Cytaa3 showed only a
      partial recovery in those 5 babies during the study period. We conclude that a
      therapeutic dose of indomethacin may cause substantial swings in brain perfusion
      and a marked and rather longstanding decrease in Cytaa3, suggesting a decrease in
      cellular oxygenation of brain tissue. Awareness of these effects may be important
      in sick preterm babies during periods of pulmonary and cardiac instability.

PMID- 8534779
TI  - Effects of calcitriol on proliferation and differentiation of human fetal
      jejunum.
AB  - Several lines of evidence suggest a role for calcitriol in the regulatory
      mechanisms of intestinal development. Using organ culture as a model, we have
      verified whether this hormone influenced the cellular proliferation and
      differentiation processes of the developing human jejunum. We show that
      calcitriol supports a proliferative process in the fetal human jejunum at 11
      weeks of gestation and a differentiating activity in samples obtained between 16
      and 20 weeks. The present data therefore suggest that calcitriol has a biphasic
      effect on the development of the human intestinal epithelium and warrants caution
      in extrapolating to human, data observed in developing rodents and human
      carcinoma cell lines.

PMID- 8534780
TI  - Umbilical vein pulsations and acid-base status at cordocentesis in growth
      retarded fetuses with absent end-diastolic velocity in umbilical artery.
AB  - The objective of this study was to examine the acid-base status in blood obtained
      at cordocentesis in growth-retarded fetuses with absent end-diastolic velocity in
      the umbilical artery and divided according to the presence or absence of
      pulsations in the umbilical vein. Twenty-six growth-retarded fetuses free from
      structural and chromosomal abnormalities were considered for this study. All the
      fetuses had absent end-diastolic velocity in the umbilical artery associated in
      11 cases (42.3%) with pulsations in the umbilical vein. Gas analysis of fetal
      blood obtained by cordocentesis was performed immediately after the Doppler
      recordings. Hypoxemia, acidemia and hypercapnia were defined respectively as the
      presence of pH or pO2 values 2 standard deviations below the normal mean for
      gestation and of pCO2 values 2 standard deviations above the normal mean for
      gestation. Fetuses with umbilical vein pulsations had lower values of pH (p < or
      = 0.001) and pO2 (p < or = 0.05) and higher values of pCO2 (p < or = 0.001) when
      compared to those without pulsations. All fetuses with pulsations were hypoxemic
      and hypercapnic and the incidence of acidemia was 90.9%. Fetuses with continuous
      blood flow in the umbilical vein, although frequently hypoxemic (80%), have pCO2
      and pH values within the normal range in 40 and 52.3% of the cases, respectively.
      In conclusion, in fetuses with absent end-diastolic velocity in the umbilical
      artery the presence of umbilical vein pulsations identifies a subgroup of fetuses
      with a more severe compromise of acid-base status. This may be useful in the
      selection of the timing of delivery of such fetuses.

PMID- 8534781
TI  - Methylxanthines increase renal calcium excretion in preterm infants.
AB  - To determine the effect of a short course of methylxanthines on renal function
      and on urinary calcium excretion, 20 premature neonates affected by apnea or
      moderate respiratory distress syndrome were randomly assigned to either a
      theophylline treatment or to a caffeine treatment group. The protocol included a
      24-hour pretreatment study period (I) and a subsequent 24-hour period (II)
      following 5 days of theophylline (loading dose 5 mg/kg i.v., maintenance dose 2.5
      mg/kg/12 h) or caffeine (loading dose 10 mg/kg i.v., maintenance dose 2.5
      mg/kg/12 h) administration. Pre- and postxanthine treatment serum sodium,
      potassium, calcium and phosphorus remained stable, while serum creatinine
      decreased significantly (p < 0.05). Furthermore, from period I to period II,
      sodium urine excretion, fractional Na excretion and creatinine clearance remained
      statistically comparable in both study groups, along with a significant increase
      (p < 0.05) in calciuria, urinary Ca/creatinine and urinary Ca/Na. Predose
      caffeine and theophylline serum levels, assessed on the 5th day of treatment,
      were 12.8 +/- 1.8 and 7.9 +/- 1.7 micrograms/ml, respectively. Compared to
      control healthy untreated prematures, the studied premature infants showed a
      statistically significant increase in urine calcium excretion (10- to 15-fold),
      which was more evident in the theophylline group. Our data suggest further
      investigation to determine the long-term renal effects of methylxanthines in
      premature neonates, to improve assessment of the risk of nephrocalcinosis and
      osteopenia, in particular in association with various diuretic therapies.

PMID- 8534782
TI  - Renal masses in the neonate.
AB  - Abdominal masses are frequent in newborn infants, two thirds being renal in
      origin. After thorough palpation of the abdomen, cystic masses must be
      differentiated from solid masses by ultrasound examination. The common benign
      cystic masses include hydronephrosis, multicystic dysplasia, polycystic disease,
      and adrenal hemorrhage. Solid masses include renal vein thrombosis, a renal
      ectopic kidney, or horseshoe kidneys. Occasionally, a renal mass may be malignant
      and correspond to congenital mesoblastic nephroma, Wilms' tumor, or fetal
      hamartoma. Whatever the nature of the renal mass, early intervention may save the
      kidney or the patient.

PMID- 8534783
TI  - Alveolar-to-vascular leakage of surfactant protein A in ventilated immature
      newborn rabbits.
AB  - We measured alveolar-to-vascular leakage of surfactant protein A (SP-A) in
      immature newborn rabbits delivered at a gestational age of 27 days. Experimental
      animals received, via a tracheal cannula, 2 ml/kg of a mixture of modified
      porcine surfactant (Curosurf, 80 mg/ml) and human recombinant SP-A (4 mg/ml).
      Littermate controls received the same volume of human SP-A in saline (4 mg/ml).
      After 30 min of artificial ventilation with a frequency of 40/min and an
      inspiration time of either 0.75 or 0.45 s, blood was sampled from the right
      ventricle and the lungs were lavaged. The content of human SP-A in serum and lung
      lavage fluid was determined with ELISA kits, and the alveolar-to-vascular leak
      expressed as the quotient of total SP-A in serum and lavage fluid. The leak in
      control animals amounted to about 2% of SP-A in lung wash and was several times
      higher in these animals than in those receiving surfactant. The leak was of the
      same order irrespective of whether the animals were ventilated with long or short
      inspiration time. We speculate that serum levels of SP-A may reflect the degree
      of lung injury in various forms of respiratory failure.

PMID- 8534784
TI  - Furosemide pharmacokinetics following intratracheal instillation in the guinea
      pig.
AB  - Inhaled furosemide has been shown to attenuate bronchospasm in asthmatics and to
      increase lung compliance in infants with bronchopulmonary dysplasia (BPD). The
      reports involving BPD used a dose of 1 mg/kg and some have failed to show an
      effect with that dose. We determined the pharmacokinetics of furosemide
      administered directly to the airway in 7 young adult male guinea pigs who
      received intravenous and intratracheal doses of furosemide. Each animal received
      a 3 mg/kg i.v. bolus, 1, 3 and 6 mg/kg i.t. in 2 ml/kg normal saline and 3 mg/kg
      i.t. in 2 ml/kg bovine extract surfactant. Blood was sampled multiple times after
      each dose. The mean fraction of the intratracheal dose absorbed was 0.50-0.60 for
      all doses. Surfactant delayed the absorption of furosemide but did not alter the
      fraction absorbed.

PMID- 8534785
TI  - Role of nitric oxide in the regulation of the cerebral circulation in the lamb
      fetus during normoxemia and hypoxemia.
AB  - The influence of nitric oxide (NO) blockade on resting tone and on hypoxia
      induced vasodilatation of the cerebral vascular bed was examined in chronically
      instrumented lamb fetuses. Total (Qbrain-tot) and regional brain blood flow were
      measured using radioactive microspheres. NO blockade was achieved by N omega
      nitro-L-arginine (NNLA) infusion into the carotid artery via a lingual artery.
      Fetal cerebral blood flow and cerebral vascular resistance (Rcer) were determined
      during normoxemia and hypoxemia and before and during infusion of L-arginine.
      During normoxemia, the brain blood flow decreased, and the resistance increased
      significantly after NNLA infusion (Qbrain-tot from 129 +/- 25 to 89 +/- 26 ml/100
      g/min, p < 0.05; Rcer from 0.46 +/- 0.03 to 0.80 +/- 0.09 mm Hg/ml/100 g/min, p <
      0.05). During hypoxemia before NNLA infusion, Qbrain-tot increased (from 129 +/-
      25 to 187 +/- 56 ml/100 g/min, p < 0.05), and Rcer decreased (from 0.46 +/- 0.03
      to 0.39 +/- 0.07 mm Hg/ml/100 g/min, p < 0.05). This vasodilatory response was
      largely blocked after NNLA (Qbrain-tot 143 +/- 45 ml/100 g/min; Rcer 0.58 +/-
      0.07 mm Hg/ml/100 g/min). The response to hypoxemia was restored after infusion
      of L-arginine (Qbrain-tot 180 +/- 47 ml/100 g/min). The resting tone of the
      cerebral vascular bed of the lamb fetus is under NO control, and NO mediates the
      cerebral vasodilatory response to hypoxia in the lamb fetus.

PMID- 8534786
TI  - Carnitine depletion in rat pups of lactating mothers given sodium pivalate.
AB  - The purpose of this study was to determine the effect of pivalate administration
      in the pregnant and lactating rat upon tissue carnitine concentrations in 1- and
      5-day-old rat pups, as well as in the lactating rats. At 17 days of gestation, 5
      rats began receiving 20 mmol/l sodium pivalate in their drinking water, while an
      additional 5 rats (control) received equimolar NaHCO3. There were no significant
      differences in litter size, or in pup weights at day 1 (p > 0.05). However, the
      pups from the pivalate group did weigh significantly less at 5 days of age
      relative to the control group. Neonatal rats in the pivalate group had
      significantly depressed levels of total carnitine in plasma, heart and liver,
      relative to the control group, at both 1 and 5 days of age. Similar depressions
      were noted for the lactating rats from the pivalate group. This study
      demonstrates the utility of pivalate administration in depressing carnitine
      concentrations in newborn rats.

PMID- 8534787
TI  - Glucocorticoid-dependent induction of the mRNA coding for argininosuccinate lyase
      in cultured fetal rat hepatocytes.
AB  - Dexamethasone increased both argininosuccinate lyase (ASL) activity and specific
      mRNA level in cultured fetal hepatocytes. Addition of various inhibitors of RNA
      synthesis showed that the increase in ASL mRNA may be related to an enhancement
      of ASL gene transcription, but not to a specific messenger stabilization. An
      apparent half-life of about 12 h for ASL mRNA was found in both untreated and
      dexamethasone-treated hepatocytes. About 30 h were necessary to observe the
      maximal effect of dexamethasone, and, in addition, both puromycin and
      cycloheximide (two inhibitors of protein synthesis) blocked the inducing effect
      of the steroid. These results suggested the involvement of intermediary
      protein(s) in the mechanism of induction of ASL mRNA by glucocorticoids.

PMID- 8534788
TI  - Cognitive and biological determinants of P300: an integrative review.
AB  - The P300 event-related brain potential (ERP) is thought to reflect neuroelectric
      activity related to cognitive processes such as attention allocation and
      activation of immediate memory. However, recent studies have provided evidence
      that the P300 also is influenced by biological processes such as fluctuations in
      the arousal state of subjects. The effects of natural (circadian, ultradian,
      seasonal, menstrual) and environmentally induced (exercise, fatigue, drugs) state
      variables on the P300 are reviewed. The findings suggest that these factors
      contribute to P300 measures and are discussed in terms of their theoretical and
      applied implications.

PMID- 8534789
TI  - A psychophysiological inquiry into the nature of the Sokolovian orienting
      response comparator model: skin conductance and EEG data.
AB  - The mechanisms which trigger the orienting response (OR) are still the subject of
      lively debate. Sokolov (1990) proposes the development of a multidimensional
      model of the physical parameters of stimulation. Recent OR research has shown
      that the skin conductance OR (SCOR) is related to task demands and controlled
      processing, although this is not so clear for central physiological indexes of
      orienting. Seventy-three subjects performed visual discriminations of stimuli
      within a warning-stimulus paradigm. The physical complexity of stimuli and their
      task relevance were manipulated within subjects, while the nonspecific effects of
      workload were controlled with a group factor. SCORs were measured concurrently
      with 1-s epochs of EEG alpha and theta power from Fz, Cz, Pz, and Oz. Neither
      index was reliably affected by the physical complexity of stimulation alone.
      However, both higher task relevance and higher workload significantly increased
      the magnitude of EEGORs and SCORs. Task averages of central and autonomic
      activity showed an overall pattern of covariation, but a second-by-second
      breakdown of EEG spectra suggests that the SCOR may be an aggregate of the
      activation of diverse brain mechanisms responsible for physiological orienting.
      The results are consistent with a model of orienting as a continuous dimension of
      resource allocation to anticipated and current task demands, rather than with the
      abrupt dichotomy between voluntary and involuntary orienting. Implications for
      the classical OR Sokolovian model are discussed.

PMID- 8534790
TI  - Event-related potential correlates of transient attention shifts to color and
      location.
AB  - Effects of selectively attending to specific combinations of stimulus location
      and color were measured by means of event-related brain potentials in a trial-by
      trial cueing paradigm. A symbolic precue was presented at the beginning of each
      trial indicating the response-relevant position and color of an upcoming
      imperative stimulus. Responses were required to infrequent target stimuli of the
      relevant color appearing at the cued location. Stimuli at attended locations
      elicited enhanced posterior N1/components as well as enhanced negativities at
      midline electrodes. No P1 enhancement was found for stimuli at the attended
      location. Attended color stimuli elicited a broad negativity starting about 220
      ms that tended to be larger for stimuli presented at attended locations. These
      results show that transient attention shifts to non-spatial features like color
      are reflected by event-related potential (ERP) effects comparable to the effects
      measured under sustained attention conditions. Transient spatial attention yields
      earlier and larger ERP effects than transient attention to color and may modulate
      the ERP effects of non-spatial attention.

PMID- 8534791
TI  - Event related potentials during covert orientation of visual attention: effects
      of cue validity and directionality.
AB  - Covert orientation of attention was studied in 30 adults who fixated warning cues
      and pressed a button at target onset. Directional cues (arrows) indicated the
      most probable (p = 0.8) side of target occurrence. Subjects responded fastest
      when validly cued, slowest to invalidly cued targets, and at an intermediate rate
      when the cue (a cross) was not directional. Directional cues took longer to
      evaluate (increased N1 and P2 latencies) and produced more focussed attention and
      greater response preparation (enhanced CNV and P3 amplitude) than non-directional
      cues. These findings indicate that the expectancy of a target can be manipulated
      by a spatial cue at three levels, sensory, attention, and response preparation,
      and lead to changes in the sensory perceptual processing of the target. Validly
      cued targets produced an increase in P1 amplitude reflecting attention enhanced
      sensory processing whereas invalidly cued targets increased N1 and P3 amplitudes
      reflecting the re-orientation of attention, and further processing and updating
      of information required of low probability stimuli respectively. P3 latency to
      invalidly cued targets was also delayed reflecting the additional processes
      required to shift attention to a new location. The P3 latency validity effect was
      smaller than that found for response time suggesting response execution may also
      be affected by spatial attention.

PMID- 8534792
TI  - A bifurcation analysis of neuronal subthreshold oscillations.
AB  - The conditions under which a noninactivating sodium current and either a
      potassium current or an inwardly rectifying cation current can generate
      subthreshold oscillations were analyzed using nonlinear dynamical techniques
      applied to a neuronal model consisting of two differential equations.
      Mathematical descriptions of the membrane currents were derived using voltage
      clamp data collected from entorhinal cortical neurons. A bifurcation analysis was
      performed using applied current as the control parameter to map the range of
      magnitudes of the sodium, potassium/cation, and leakage conductances over which
      subthreshold oscillations exist. The threshold of the potassium/cation current
      was an important determinant of the robustness of oscillatory behavior. The
      activation time constant of the potassium/cation current largely determined the
      frequency range of emergent oscillations. This result implicates the slow inward
      rectifier or an as yet undescribed slow outward current in entorhinal cortical
      oscillations; the latter explanation, while more speculative, is more consistent
      with the pharmacological properties of subthreshold oscillations and gives
      oscillations over a larger current range. The shallowness of the sodium
      activation curve confined emergent oscillations to rise gradually rather than
      abruptly and extended the current range over which the model oscillated.

PMID- 8534793
TI  - The secretory granule matrix-electrolyte interface: a homologue of the p-n
      rectifying junction.
AB  - When placed at the tip of a glass micropipette electrode the polymeric matrix of
      the secretory granule behaves like a diode. The measured current was 100-fold
      greater at negative potentials compared to positive potentials, and up to sixfold
      greater than that measured with the pipette alone. By manipulating the geometry
      of the electric field we show that these electrical properties result from
      focusing an electric field at the gel-electrolyte interface. We also show, by
      using pulsed-laser imaging with fluorescein as the ionic probe, that there is a
      rapid accumulation and depletion of ions at the gel-electrolyte interface. A
      voltage pulse of -9 V applied to the gel caused a severalfold increase in the
      fluorescence intensity within 5 ms. This correlated with an increase in the
      measured current (approximately 1 microA). In contrast, within 5 ms of applying
      +9 V we recorded a decrease in the fluorescence intensity, which paralleled the
      twofold decrease in the measured current. This is similar to a p-n junction where
      an applied voltage causes the accumulation and depletion of charge carriers.
      Using synthetic gels (diameter 3-6 microns) with different charge characteristics
      we observed no rectification of the current with neutral gels and confirmed that
      rectification and amplification of the current were dependent on the fixed charge
      within a gel. In addition, we modeled the conduction at the gel-electrolyte
      interface using the Nernst-Planck electrodiffusion equation and accurately fitted
      the experimental current-voltage relationships. This study provides some insight
      into how biological interfaces may function. For example, we suggest that
      neurotransmitter release during exocytosis could be regulated by voltage-induced
      accumulation and depletion of ions at the interface between the secretory granule
      and the fusion pore.

PMID- 8534794
TI  - Incorporation of surface tension into molecular dynamics simulation of an
      interface: a fluid phase lipid bilayer membrane.
AB  - In this paper we report on the molecular dynamics simulation of a fluid phase
      hydrated dimyristoylphosphatidylcholine bilayer. The initial configuration of the
      lipid was the x-ray crystal structure. A distinctive feature of this simulation
      is that, upon heating the system, the fluid phase emerged from parameters,
      initial conditions, and boundary conditions determined independently of the
      collective properties of the fluid phase. The initial conditions did not include
      chain disorder characteristic of the fluid phase. The partial charges on the
      lipids were determined by ab initio self-consistent field calculations and
      required no adjustment to produce a fluid phase. The boundary conditions were
      constant pressure and temperature. Thus the membrane was not explicitly required
      to assume an area/phospholipid molecule thought to be characteristic of the fluid
      phase, as is the case in constant volume simulations. Normal to the membrane
      plane, the pressure was 1 atmosphere, corresponding to the normal laboratory
      situation. Parallel to the membrane plane a negative pressure of -100 atmospheres
      was applied, derived from the measured surface tension of a monolayer at an air
      water interface. The measured features of the computed membrane are generally in
      close agreement with experiment. Our results confirm the concept that, for
      appropriately matched temperature and surface pressure, a monolayer is a close
      approximation to one-half of a bilayer. Our results suggest that the surface area
      per phospholipid molecule for fluid phosphatidylcholine bilayer membranes is
      smaller than has generally been assumed in computational studies at constant
      volume. Our results confirm that the basis of the measured dipole potential is
      primarily water orientations and also suggest the presence of potential barriers
      for the movement of positive charges across the water-headgroup interfacial
      region of the phospholipid.

PMID- 8534795
TI  - Equilibration and exchange of fluorescently labeled molecules in skinned skeletal
      muscle fibers visualized by confocal microscopy.
AB  - Confocal laser fluorescence microscopy was used to study in real time under
      nearly physiological conditions the equilibration and exchange characteristics of
      several different fluorescently labeled molecules into chemically skinned,
      unfixed skeletal muscle fibers of rabbit psoas. The time required for
      equilibration was found to vary widely from a few minutes up to several days.
      Specific interactions of molecules with myofibrillar structures seem to slow down
      equilibration significantly. Time for equilibration, therefore, cannot simply be
      predicted from diffusion parameters in solution. Specific interactions resulted
      in characteristic labeling patterns for molecules like creatine kinase (muscle
      type), pyruvate kinase, actin-binding IgG, and others. For the very slowly
      equilibrating Rh-NEM-S1, changes in affinity upon binding to actin in the absence
      of calcium and subsequent slow cooperative activation, beginning at the free end
      of the filament at the H-zone, were observed. In the presence of calcium,
      however, binding of Rh-NEM-S1 was homogeneous along the whole actin filament from
      the very beginning of equilibration. The dissociation properties of the dynamic
      interactions were analyzed using a chase protocol. Even molecules that bind with
      rather high affinity and that can be removed only by applying extreme
      experimental conditions like Rh-phalloidine or Rh-troponin could be displaced
      easily by unlabeled homologous molecules.

PMID- 8534796
TI  - The thermodynamic response of soft biological tissues to pulsed ultraviolet laser
      irradiation.
AB  - The physical mechanisms that enable short pulses of high-intensity ultraviolet
      laser radiation to remove tissue, in a process known as laser ablation, remain
      obscure. The thermodynamic response of biological tissue to pulsed laser
      irradiation was investigated by measuring and subsequently analyzing the stress
      transients generated by pulsed argon fluorine (ArF, lambda = 193 nm) and krypton
      fluorine (KrF, lambda = 248 nm) excimer laser irradiation of porcine dermis using
      thin-film piezoelectric transducers. For radiant exposures that do not cause
      material removal, the stress transients are consistent with rapid thermal
      expansion of the tissue. At the threshold radiant exposure for ablation, the peak
      stress amplitude generated by 248 nm irradiation is more than an order of
      magnitude larger than that produced by 193 nm irradiation. For radiant exposures
      where material removal is achieved, the temporal structure of the stress
      transient indicates that the onset of material removal occurs during irradiation.
      In this regime, the variation of the peak compressive stress with radiant
      exposure is consistent with laser-induced rapid surface vaporization. For 193 nm
      irradiation, ionization of the ablated material occurs at even greater radiant
      exposures and is accompanied by a change in the variation of peak stress with
      radiant exposure consistent with a plasma-mediated ablation process. These
      results suggest that absorption of ultraviolet laser radiation by the
      extracellular matrix of tissue leads to decomposition of tissue on the time scale
      of the laser pulse. The difference in volumetric energy density at ablation
      threshold between the two wavelengths indicates that the larger stresses
      generated by 248 nm irradiation may facilitate the onset of material removal.
      However, once material removal is achieved, the stress measurements demonstrate
      that energy not directly responsible for target decomposition contributes to
      increasing the specific energy of the plume (and plasma, when present), which
      drives the gas dynamic expansion of ablated material. This provides direct
      evidence that ultraviolet laser ablation of soft biological tissues is a surface
      mediated process and not explosive in nature.

PMID- 8534797
TI  - Voltage sensing by fluorescence resonance energy transfer in single cells.
AB  - A new mechanism has been developed for achieving fast ratiometric voltage
      sensitive fluorescence changes in single cells using fluorescence resonance
      energy transfer. The mechanism is based on hydrophobic fluorescent anions that
      rapidly redistribute from one face of the plasma membrane to the other according
      to the Nernst equation. A voltage-sensitive fluorescent readout is created by
      labeling the extracellular surface of the cell with a second fluorophore, here a
      fluorescently labeled lectin, that can undergo energy transfer with the membrane
      bound sensor. Fluorescence resonance energy transfer between the two fluorophores
      is disrupted when the membrane potential is depolarized, because the anion is
      pulled to the intracellular surface of the plasma membrane far from the lectin.
      Bis-(1,3-dialkyl-2-thiobarbiturate)-trimethineoxonols, where alkyl is n-hexyl and
      n-decyl (DiSBA-C6-(3) and DiSBA-C10-(3), respectively) can function as donors to
      Texas Red labeled wheat germ agglutinin (TR-WGA) and acceptors from fluorescein
      labeled lectin (FI-WGA). In voltage-clamped fibroblasts, the translocation of
      these oxonols is measured as a displacement current with a time constant of
      approximately 2 ms for 100 mV depolarization at 20 degrees C, which equals the
      speed of the fluorescence changes. Fluorescence ratio changes of between 4% and
      34% were observed for a 100-mV depolarization in fibroblasts, astrocytoma cells,
      beating cardiac myocytes, and B104 neuroblastoma cells. The large fluorescence
      changes allow high-speed confocal imaging.

PMID- 8534798
TI  - XRayView: a teaching aid for X-ray crystallography.
AB  - A software package, XRayView, has been developed that uses interactive computer
      graphics to introduce basic concepts of x-ray diffraction by crystals, including
      the reciprocal lattice, the Ewald sphere construction, Laue cones, the wavelength
      dependence of the reciprocal lattice, primitive and centered lattices and
      systematic extinctions, rotation photography. Laue photography, space group
      determination and Laue group symmetry, and the alignment of crystals by
      examination of reciprocal space. XRayView is designed with "user-friendliness" in
      mind, using pull-down menus to control the program. Many of the experiences of
      using real x-ray diffraction equipment to examine crystalline diffraction can be
      simulated. Exercises are available on-line to guide the users through many
      typical x-ray diffraction experiments.

PMID- 8534799
TI  - A cellular automaton model for the proliferation of migrating contact-inhibited
      cells.
AB  - A cellular automaton is used to develop a model describing the proliferation
      dynamics of populations of migrating, contact-inhibited cells. Simulations are
      carried out on two-dimensional networks of computational sites that are finite
      state automata. The discrete model incorporates all the essential features of the
      cell locomotion and division processes, including the complicated dynamic
      phenomena occurring when cells collide. In addition, model parameters can be
      evaluated by using data from long-term tracking and analysis of cell locomotion.
      Simulation results are analyzed to determine how the competing processes of
      contact inhibition and cell migration affect the proliferation rates. The
      relation between cell density and contact inhibition is probed by following the
      temporal evolution of the population-average speed of locomotion. Our results
      show that the seeding cell density, the population-average speed of locomotion,
      and the spatial distribution of the seed cells are crucial parameters in
      determining the temporal evolution of cell proliferation rates. The model
      successfully predicts the effect of cell motility on the growth of isolated
      megacolonies of keratinocytes, and simulation results agree very well with
      experimental data. Model predictions also agree well with experimentally measured
      proliferation rates of bovine pulmonary artery endothelial cells (BPAE) cultured
      in the presence of a growth factor (bFGF) that up-regulates cell motility.

PMID- 8534800
TI  - Interaction of small peptides with lipid bilayers.
AB  - Molecular dynamics simulations of the tripeptide Ala-Phe-Ala-O-tert-butyl
      interacting with dimyristoylphosphatidylcholine lipid bilayers have been carried
      out. The lipid and aqueous environments of the peptide, the alkyl chain order,
      and the lipid and peptide dynamics have been investigated with use of density
      profiles, radial distribution functions, alkyl chain order parameter profiles,
      and time correlation functions. It appears that the alkyl chain region
      accommodates the peptides in the bilayer with minimal perturbation to this
      region. The peptide dynamics in the bilayer bound form has been compared with
      that of the free peptide in water. The peptide structure does not vary on the
      simulation time scale (of the order of hundreds of picoseconds) compared with the
      solution structure in which a random structure is observed.

PMID- 8534801
TI  - A stochastic model of leukocyte rolling.
AB  - Selectin-mediated leukocyte rolling under flow is an important process in
      leukocyte recruitment during inflammation. The rolling motion of individual cells
      has been observed to fluctuate randomly both in vivo and in vitro. This paper
      presents a stochastic model of the micromechanics of cell rolling and provides an
      analytical method of treating experimental data. For a homogeneous cell
      population, the velocity distribution is obtained in an analytical form, which is
      in good agreement with experimentally determined velocity histograms obtained
      previously. For a heterogeneous cell population, the model provides a simple,
      analytical method of separating the contributions of temporal fluctuations and
      population heterogeneity to the variance of measured rolling velocities. The
      model also links the mean and variance of rolling velocities to the molecular
      events underlying the observed cellular motion, allowing characterization of the
      distribution and release rate of the clusters of molecular bonds that tether the
      cell to substratum. Applying the model to the analysis of data obtained for
      neutrophils rolling on an E-selectin-coated surface at a wall shear stress of 1.2
      dyn/cm2 yields estimations of the average distance between bond clusters
      (approximately micron) and the average time duration of a bond cluster resisting
      the applied fluid force (approximately 0.5 s).

PMID- 8534802
TI  - Genetic-algorithm selection of a regulatory structure that directs flux in a
      simple metabolic model.
AB  - A genetic algorithm (GA) is used to optimize parameters for allosteric regulation
      of enzymes in a model of a metabolic futile cycle, in which two metabolites are
      interconverted by a pair of irreversible enzymatic reactions. The cycle is
      regulated by end products of the surrounding pathway. The optimization criterion
      for the GA is the proper direction of chemical flux in the regulated cycle toward
      one or the other end product in response to a simple, time-dependent model of
      biochemical "need" based on externally imposed variation of the end product
      concentrations. An energetic cost, to be held to a minimum, is also imposed on
      the operation of the cycle. The best-performing individuals selected by the GA
      are found to switch rapidly the direction of net flux according to need. In
      different "environments" (specific time courses of end product concentrations),
      the GA produces better- or poorer-performing individuals. In some cases
      "generalists" and "specialists" are produced. The present approach provides,
      purely as a consequence of formally specifying the task of flux direction, the
      new result of numerical confirmation, in a simple model, of the intuition that
      negative feedback and reciprocal regulation are important for good flux direction
      in arbitrary environments, and gives rise to a diversity of structures,
      suggestive of the results of biological evolution.

PMID- 8534803
TI  - Transbilayer pores formed by beta-barrels: molecular modeling of pore structures
      and properties.
AB  - Transmembrane beta-barrels, first observed in bacterial porins, are possible
      models for a number of membrane channels. Restrained molecular dynamics
      simulations based on idealized C alpha beta templates have been used to generate
      models of such beta-barrels. Model beta-barrels have been analyzed in terms of
      their conformational, energetic, and pore properties. Model beta-barrels formed
      by N = 4, 8, 12 and 16 anti-parallel Ala10 strands have been developed. For each
      N, beta-barrels with shear numbers S = N to 2N have been modeled. In all beta
      barrel models the constituent beta-strands adopt a pronounced right-handed twist.
      Interstrand interactions are of approximately equal stability for all models with
      N > or = 8, whereas such interactions are weaker for the N = 4 beta-barrels. In N
      = 4 beta-barrels the pore is too narrow (minimum radius approximately 0.6 A) to
      allow ion permeation. For N > or = 8, the pore radius depends on both N and S;
      for a given value of N an increase in S from N to 2N is predicted to result in an
      approximately threefold increase in pore conductance. Calculated maximal
      conductances for the beta-barrel models are compared with experimental values for
      porins and for K+ channels.

PMID- 8534804
TI  - Computation of the dipole moments of proteins.
AB  - A simple and computationally feasible procedure for the calculation of net
      charges and dipole moments of proteins at arbitrary pH and salt conditions is
      described. The method is intended to provide data that may be compared to the
      results of transient electric dichroism experiments on protein solutions. The
      procedure consists of three major steps: (i) calculation of self energies and
      interaction energies for ionizable groups in the protein by using the finite
      difference Poisson-Boltzmann method, (ii) determination of the position of the
      center of diffusion (to which the calculated dipole moment refers) and the
      extinction coefficient tensor for the protein, and (iii) generation of the
      equilibrium distribution of protonation states of the protein by a Monte Carlo
      procedure, from which mean and root-mean-square dipole moments and optical
      anisotropies are calculated. The procedure is applied to 12 proteins. It is shown
      that it gives hydrodynamic and electrical parameters for proteins in good
      agreement with experimental data.

PMID- 8534805
TI  - Double-stranded DNA organization in bacteriophage heads: an alternative toroid
      based model.
AB  - Studies of the organization of double-stranded DNA within bacteriophage heads
      during the past four decades have produced a wealth of data. However, despite the
      presentation of numerous models, the true organization of DNA within phage heads
      remains unresolved. The observations of toroidal DNA structures in electron
      micrographs of phage lysates have long been cited as support for the organization
      of DNA in a spool-like fashion. This particular model, like all other models, has
      not been found to be consistent will all available data. Recently we proposed
      that DNA within toroidal condensates produced in vitro is organized in a manner
      significantly different from that suggested by the spool model. This new toroid
      model has allowed the development of an alternative model for DNA organization
      within bacteriophage heads that is consistent with a wide range of biophysical
      data. Here we propose that bacteriophage DNA is packaged in a toroid that is
      folded into a highly compact structure.

PMID- 8534806
TI  - Activation of the M2 ion channel of influenza virus: a role for the transmembrane
      domain histidine residue.
AB  - To test the hypothesis that transmembrane domain histidine residue 37 of the M2
      ion channel of influenza A virus mediates the low pH-induced activation of the
      channel, the residue was changed to glycine, glutamate, arginine, or lysine. The
      wild-type and altered M2 proteins were expressed in oocytes of Xenopus laevis and
      membrane currents were recorded. The mass of protein expressed in individual
      oocytes was measured using quantitative immunoblotting and correlated with
      membrane currents. Oocytes expressing the M2-H37G protein had a voltage
      independent conductance with current-voltage relationship similar to that of the
      wild-type M2 channel. The conductance of the M2-H37G protein was reversibly
      inhibited by the M2 ion channel blocker amantadine and was only very slightly
      modulated by changes in pHout over the range pH 5.4 to pH 8.2. Oocytes expressing
      the M2-H37E protein also had a voltage-independent conductance with a current
      voltage relationship similar to that of the wild-type M2 channel. The conductance
      of the M2-H37E protein was reversibly inhibited by amantadine and was also only
      very slightly modulated by changes in pHout over the range pH 5.4 to pH 8.2.
      These slight alterations in conductance of the mutant ion channels on changes in
      pHout are in striking contrast to the 50-fold change in conductance seen for the
      wild-type M2 channel over the range pH 4.5 to pH 8.2. The specific activity of
      the M2-H37G protein was 1.36 +/- 0.37 microA/ng and the specific activity of the
      M2-H37E protein was 30 +/- 3 microA/ng at pH 6.2. These values of specific
      activity greatly exceed that of the wild-type protein at the same pH (0.16 + 0.01
      micro A/ng). Oocytes expressing the M2-H37K and M2-H37R mutant proteins could not
      be studied because the oocytes did not survive more than a few hours in culture.
      Oocytes expressing the M2-H37E mutant protein also had a voltage-activated Cl-
      conductance that was observed only for oocytes that expressed a mass of protein
      exceeding a large threshold value. These results are consistent with protonation
      of histidine residue 37 as an essential step in the activation of the wild-type
      M2 ion channel.

PMID- 8534807
TI  - Interaction of poly(ethylene-glycols) with air-water interfaces and lipid
      monolayers: investigations on surface pressure and surface potential.
AB  - We have characterized the surface activity of different-sized poly(ethylene
      glycols) (PEG; M(r) 200-100,000 Da) in the presence or absence of lipid
      monolayers and over a wide range of bulk PEG concentrations (10(-8)-10% w/v).
      Measurements of the surface potential and surface pressure demonstrate that PEGs
      interact with the air-water and lipid-water interfaces. Without lipid, PEG added
      either to the subphase or to the air-water interface forms relatively stable
      monolayers. Except for very low molecular weight polymers (PEGs < 1000 Da), low
      concentrations of PEG in the subphase (between 10(-5) and 10(-4)% w/v) increase
      the surface potential from zero (with respect to the potential of a pure air
      water interface) to a plateau value of approximately 440 mV. At much higher
      polymer concentrations, > 10(-1)% (w/v), depending on the molecular weight of the
      PEG and corresponding to the concentration at which the polymers in solution are
      likely to overlap, the surface potential decreases. High concentrations of PEG in
      the subphase cause a similar decrease in the surface potential of densely packed
      lipid monolayers spread from either diphytanoyl phosphatidylcholine (DPhPC),
      dipalmitoyl phosphatidylcholine (DPPC), or dioleoyl phosphatidylserine (DOPS).
      Adding PEG as a monolayer at the air-water interface also affects the surface
      activity of DPhPC or DPPC monolayers. At low lipid concentration, the surface
      pressure and potential are determined by the polymer. For intermediate lipid
      concentrations, the surface pressure-area and surface potential-area isotherms
      show that the effects due to lipid and PEG are not always additive and that the
      polymer's effect is distinct for the two lipids. When PEG-lipid-mixed monolayers
      are compressed to surface pressures greater than the collapse pressure for a PEG
      monolayer, the surface pressure-area and surface potential-area isotherms
      approach that of the lipid alone, suggesting that for this experimental condition
      PEG is expelled from the interface.

PMID- 8534808
TI  - A Monte Carlo model of fd and Pf1 coat proteins in lipid membranes.
AB  - A Monte Carlo Dynamics simulation was used to investigate the behavior of
      filamentous bacteriophage coat proteins in a model membrane environment. Our
      simulation agrees with the previous experimental observations that despite the
      low sequence similarity between the major coat proteins of Pf1 and fd
      bacteriophages, their structure in the membrane environment is very similar.
      These results support the hypothesis that the hydrophobic effect exerts an
      important influence on membrane protein structure. The model may also be used for
      modeling the insertion and transport processes in protein-membrane systems. The
      example of fd protein was also used as a test of sensitivity of our model to
      temperature, thickness of the hydrocarbon phase, and simulation time. In all
      cases, the results were independent (over the tested range) of the particular
      values of the parameters.

PMID- 8534809
TI  - Localized contact formation by erythrocyte membranes: electrostatic effects.
AB  - The topology of the contact seam of human erythrocytes adhered by dextran, an
      uncharged polymer, has been examined. Particular attention has been paid to the
      influence of electrostatic intermembrane interactions since their magnitude and
      range can be accurately estimated. Normal cells formed a continuous seam, whereas
      erythrocytes with pronase-modified glycocalices formed localized contact points
      on adhesion in 72 kDa dextran in buffered 145 mM NaCl. The dependence of the
      inter-contact distance lambda on dextran concentration [D] over the range 2-6%
      w/v, was given by lambda = C[D]-0.62, where C was a constant. The index of [D]
      was independent of dextran molecular mass over the range 20 to 450 kDa. The inter
      contact distance for pronase-pretreated cells in 6% w/v 72 kDa dextran increased
      from 0.78 to 1.4 microns as [NaCl] was reduced through the range 145 to 90 mM and
      the suspending phase was maintained at isotonicity by using sorbitol to replace
      NaCl. The formation and lateral separation of the contact points are discussed
      from the perspective of linear interfacial instability theory. The theory allows
      a quantitative explanation for the experimentally observed dependence of inter
      contact distance and of disturbance growth rate on change in electrostatic
      interaction. The results suggest that the dominant wavelength, determining the
      inter-contact distance, is established on approaching membranes when the layers
      of cell surface charge are separated by a perpendicular distance of < 14 nm
      (bilayer separation of 24 nm).

PMID- 8534810
TI  - Thermodynamics of interdigitated phases of phosphatidylcholine in glycerol.
AB  - Comparison of the electron spin resonance spectra of phosphatidylcholines spin
      labeled in the sn-2 chain at a position close to the polar region and close to
      the methyl terminus indicate that symmetrical saturated diacyl
      phosphatidylcholines with odd and even chain lengths from 13 to 20 C-atoms (and
      probably also 12 C-atoms) have gel phases in which the chains are interdigitated
      when dispersed in glycerol. The chain-length dependences of the chain-melting
      transition enthalpies and entropies are similar for phosphatidylcholines
      dispersed in glycerol and in water, but the negative end contributions are
      smaller for phosphatidylcholines dispersed in glycerol than for those dispersed
      in water: d delta Ht/dCH2 = 1.48 (1.43) kcal.mol-1, d delta St/dCH2 = 3.9 (4.0)
      cal.mol-1K-1, and delta H o = -12.9 (-15.0) kcal.mol-1, delta S o = -29 (-40)
      cal.mol-1K-1, respectively, for dispersions in glycerol (water). These
      differences reflect the interfacial energetics in glycerol and in water, and the
      different structure of the interdigitated gel phase.

PMID- 8534811
TI  - Analysis of saturation transfer electron paramagnetic resonance spectra of a spin
      labeled integral membrane protein, band 3, in terms of the uniaxial rotational
      diffusion model.
AB  - Algorithms have been developed for the calculation of saturation transfer
      electron paramagnetic resonance (ST-EPR) spectra of a nitroxide spin-label
      assuming uniaxial rotational diffusion, a model that is frequently used to
      describe the global rotational dynamics of large integral membrane proteins. One
      algorithm explicitly includes terms describing Zeeman overmodulation effects,
      whereas the second more rapid algorithm treats these effects approximately using
      modified electron spin-lattice and spin-spin relaxation times. Simulations are
      presented to demonstrate the sensitivity of X-band ST-EPR spectra to the rate of
      uniaxial rotational diffusion and the orientation of the nitroxide probe with
      respect to the diffusion axis. Results obtained by using the algorithms
      presented, which are based on the transition-rate formalism, are in close
      agreement with those obtained by using an eigenfunction expansion approach. The
      effects of various approximations used in the simulation algorithms are
      considered in detail. Optimizing the transition-rate formalism to model uniaxial
      rotational diffusion results in over an order of magnitude reduction in
      computation time while allowing treatment of nonaxial A- and g-tensors. The
      algorithms presented here are used to perform nonlinear least-squares analyses of
      ST-EPR spectra of the anion exchange protein of the human erythrocyte membrane,
      band 3, which has been affinity spin-labeled with a recently developed
      dihydrostilbene disulfonate derivative, [15N,2H13]-SL-H2DADS-MAL. These results
      suggest that all copies of band 3 present in intact erythrocytes undergo
      rotational diffusion about the membrane normal axis at a rate consistent with a
      band 3 dimer.

PMID- 8534812
TI  - Definition of lipid membrane structural parameters from neutronographic
      experiments with the help of the strip function model.
AB  - Neutron diffraction is an effective method for investigating model and biological
      membranes. Yet, to obtain accurate structural information it is necessary to use
      deuterium labels and much time is needed to acquire experimental data as there
      are a large number of diffraction reflections to register. This paper offers a
      way to define the hydrophobic boundary position in lipid membranes with high
      accuracy and for this purpose it is sufficient to take into consideration three
      structural factors. The method is based on modeling the density of the neutron
      diffraction amplitude rho(x) in the direction of the bilayer plane normal by
      means of a strip function, but it also takes into consideration the fact that the
      multiplication of the strip function amplitude rho i by the step width zi-zi-1
      makes the sum of neutron scattering amplitudes of the atoms included in the step
      region. On the basis of the analysis of a large number of experimental data for
      different membranes, the effectiveness of this method in the determination of the
      position of hydrophilic/hydrophobic boundary is demonstrated, including the case
      of various rho(x) modifications in the region of polar heads and also the
      different phase states of membranes. However, it is shown in the present paper
      that the strip function model is not an adequate instrument for the determination
      of other structural parameters of membranes.

PMID- 8534813
TI  - Radial organization of interstitial exchange pathway and influence of collagen in
      synovium.
AB  - The synovial intercellular space is the path by which water, nutrients,
      cytokines, and macromolecules enter and leave the joint cavity. In this study two
      structural factors influencing synovial permeability were quantified by
      morphometry (Delesse's principle) of synovial electronmicrographs (rabbit knee),
      namely interstitial volume fraction Vv.1 and the fraction of the interstitium
      obstructed by collagen fibrils. Mean Vv.1 across the full thickness was 0.66 +/-
      0.03 SEM (n = 11); but Vv.1 actually varied systematically with depth normal to
      the surface, increasing nonlinearly from 0.40 +/- 0.04 (n = 5 joints) near the
      free surface to 0.92 +/- 0.02 near the subsynovial interface. Tending to offset
      this increase in transport space, however, the space "blocked" by collagen
      fibrils also increased nonlinearly with depth. Bundles of collagen fibrils
      occupied 13.6 +/- 2.4% of interstitial volume close to the free surface but 49 +/
      4.8% near the subsynovial surface (full-thickness average, 40.5 +/- 3.5%), with
      fibrils accounting for 48.6-57.1% of the bundle space. Because of the two
      counteracting compositional gradients, the space available for fibril-excluded
      transport (hydraulic flow and macromolecular diffusion) was relatively constant >
      4 microns below the surface but constricted at the synovium-cavity interface. The
      space available to extracellular polymers was only 51-53% of tissue volume,
      raising their effective concentration and hence the lining's resistance to flow
      and ability to confine the synovial fluid.

PMID- 8534814
TI  - Characterization of Langmuir-Blodgett films of rhodopsin: thermal stability
      studies.
AB  - Two-dimensional close packing of purified bovine rhodopsin, made by the Langmuir
      Blodgett technique, was characterized by small angle x-ray scattering and
      nanogravimetric measurements. The area occupied by a molecule of rhodopsin in the
      film was approximately 1100 Angstrum2 and the periodicity of the layers resulted
      in 59 Angstrum. The circular dichroism measurements showed that bleached
      rhodopsin in Langmuir-Blodgett film had high thermal stability, in fact, reaching
      a temperature of 150 degrees C without a loss of the secondary structure.
      Moreover, when the film was made up in the dark, rhodopsin maintained its
      stability up to at least 200 degrees C and its characteristic absorbance peak at
      500 nm up to about 90 degrees C.

PMID- 8534815
TI  - Lipid vesicle adsorption versus formation of planar bilayers on solid surfaces.
AB  - The absorption and spreading behavior of lipid vesicles composed of either
      palmitoyloleoylphosphatidylcholine (POPC) or Escherichia coli lipid upon contact
      with a glass surface was examined by fluorescence measurements. Fluorescently
      labeled lipids were used to determine 1) the amount of lipid adsorbed at the
      surface, 2) the extent of fusion of the vesicles upon contact with the surface,
      3) the ability of the adsorbed lipids to undergo lateral diffusion, and 4) the
      accessibility of the adsorbed lipids by external water soluble molecules. The
      results of these measurements indicate that POPC vesicles spread on the surface
      and form a supported planar bilayer, whereas E. coli lipid vesicles adsorb to the
      surface and form a supported vesicle layer. Supported planar bilayers were found
      to be permeable for small molecules, whereas supported vesicles were impermeable
      and thus represented immobilized, topologically separate compartments.

PMID- 8534816
TI  - Phase stability of phosphatidylcholines in dimethylsulfoxide solutions.
AB  - The temperature dependence of the phase stability of dispersions of dimyristoyl,
      dipalmitoyl, and distearoyl derivatives of phosphatidylcholines in excess aqueous
      dimethylsulfoxide has been examined by differential scanning calorimetry and
      synchrotron x-ray diffraction methods. There was a close correlation between the
      enthalpic transitions and the structural changes associated with the pre- and
      main transitions of the phospholipids in the range of concentrations up to mole
      fractions of dimethylsulfoxide in water of 0.1333. The temperature of the pre-
      and main transitions of the three phospholipids were found to increase linearly
      with increasing mole fraction of dimethylsulfoxide. The difference in phase
      stability between the lamellar gel and ripple phases induced by increasing
      dimethylsulfoxide concentration resulted in disappearance of the ripple phase and
      direct transition between lamellar gel and lamellar liquid-crystal phases. The
      effect of changing the properties of the solvent by the addition of
      dimethylsulfoxide on the dimensions of dipalmitoylphosphatidylcholine and solvent
      layers of the bilayer repeat structure has been determined from electron density
      distribution calculations. The lamellar repeat spacing recorded at 25 degrees C
      decreased from 6.36 nm in aqueous dispersion to 6.04 nm in a dispersion
      containing a mole fraction of 0.1105 dimethylsulfoxide. The results indicate that
      dipole interactions between solvent and phospholipid and dielectric properties of
      the solvent are important factors in the determination of the structure of
      saturated phosphatidylcholines.

PMID- 8534817
TI  - Structural and thermotropic properties of calcium-dimyristoylphosphatidic acid
      complexes at acidic and neutral pH conditions.
AB  - Two kinds of calcium-dimyristoylphosphatidic acid (DMPA) complexes at acidic and
      neutral pH conditions were prepared in the following ways. The complex at pH 4
      was obtained by adding Ca2+ to DMPA dispersion in pure water. On the other hand,
      the complex at pH 7.4 was obtained by adding Ca2+ to DMPA dispersion in the
      presence of NaOH. The stoichiometries of Ca2+ ion to DMPA molecule are 0.5-0.67
      and approximately 1 for the complexes at pH 4 and 7.4, respectively. Static x-ray
      diffraction shows that the hydrocarbon chains of the Ca(2+)-DMPA complex at pH 4
      at 20 degrees C are more tightly packed than those of the complex at pH 7.4 at 20
      degrees C. Furthermore, the complex at pH 4 at 20 degrees C gives rise to several
      reflections that might be related to the ordered arrangement of the Ca2+ ions.
      These results indicate that the structure of the complex at pH 4 is crystalline
      like. In the differential scanning calorimetry (DSC) thermogram, the complex at
      pH 7.4 undergoes no phase transition in a temperature range between 30 and 80
      degrees C. On the other hand, in the DSC thermogram for the complex at pH 4, a
      peak appears at 65.8 degrees C in the first heating scan. In the successive
      second heating scan, a transition peak appears at 63.5 degrees C. In connection
      with the DSC results, the structural changes associated with these phase
      transitions were studied with temperature-scan x-ray diffraction. In the first
      heating scan, although a peak appears at 65.80C in the DSC thermogram, the
      hydrocarbon chain packing gradually converts from an orthorhombic lattice to a
      hexagonal lattice near 52 degree C, and successively the chain melting phase
      transition occurs near 670C. In the second heating scan, the hydrocarbon chains
      are packed in a hexagonal lattice over the whole temperature range and the chain
      melting phase transition occurs near 63.5 degree C. Therefore,the Ca2+-DMPA
      complex at pH 4 has a metastable state. The metastable state transforms to a
      stable state by maintaining the complex at pH 4 for about 90 h at 200C.

PMID- 8534818
TI  - Temperature dependence of the repulsive pressure between phosphatidylcholine
      bilayers.
AB  - Bilayer structure and interbilayer repulsive pressure were measured from 5 to 50
      degrees C by the osmotic stress/x-ray diffraction method for both gel and liquid
      crystalline phase lipid bilayers. For gel phase dibehenoylphosphatidylcholine
      (DBPC) the bilayer thickness and pressure-distance relations were nearly
      temperature-independent, and at full hydration the equilibrium fluid spacing
      increased approximately 1 A, from 10 A at 5 degrees C to 11 A at 50 degrees C. In
      contrast, for liquid crystalline phase egg phosphatidylcholine (EPC), the bilayer
      thickness, equilibrium fluid spacing, and pressure-distance relation were all
      markedly temperature-dependent. As the temperature was increased from 5 to 50
      degrees C the EPC bilayer thickness decreased approximately 4 A, and the
      equilibrium fluid spacing increased from 14 to 21 A. Over this temperature range
      there was little change in the pressure-distance relation for fluid spacings less
      than approximately 10 A, but a substantial increase in the total pressure for
      fluid spacings greater than 10 A. These data show that for both gel and liquid
      crystalline bilayers there is a short-range repulsive pressure that is nearly
      temperature-independent, whereas for liquid crystalline bilayers there is also a
      longer-range pressure that increases with temperature. From analysis of the
      energetics of dehydration we argue that the temperature-independent short-range
      pressure is consistent with a hydration pressure due to polarization or
      electrostriction of water molecules by the phosphorylcholine moiety. For the
      liquid crystalline phase, the 7 A increase in equilibrium fluid spacing with
      increasing temperature can be predicted by an increase in the undulation pressure
      as a consequence of a temperature-dependent decrease in bilayer bending modulus.

PMID- 8534819
TI  - Approximating the isometric force-calcium relation of intact frog muscle using
      skinned fibers.
AB  - In previous papers we used estimates of the composition of frog muscle and
      calculations involving the likely fixed charge density in myofibrils to propose
      bathing solutions for skinned fibers, which best mimic the normal intracellular
      milieu of intact muscle fibers. We tested predictions of this calculation using
      measurements of the potential across the boundary of skinned frog muscle fibers
      bathed in this solution. The average potential was -3.1 mV, close to that
      predicted from a simple Donnan equilibrium. The contribution of ATP hydrolysis to
      a diffusion potential was probably small because addition of 1 mM vanadate to the
      solution decreased the fiber actomyosin ATPase rate (measured by high-performance
      liquid chromatography) by at least 73% but had little effect on the measured
      potential. Using these solutions, we obtained force-pCa curves from mechanically
      skinned fibers at three different temperatures, allowing the solution pH to
      change with temperature in the same fashion as the intracellular pH of intact
      fibers varies with temperature. The bath concentration of Ca2+ required for half
      maximal activation of isometric force was 1.45 microM (22 degrees C, pH 7.18),
      2.58 microM (16 degrees C, pH 7.25), and 3.36 microM (5 degrees C, pH 7.59). The
      [Ca2+] at the threshold of activation at 16 degrees C was approximately 1 microM,
      in good agreement with estimates of threshold [Ca2+] in intact frog muscle
      fibers.

PMID- 8534820
TI  - Sliding distance per ATP molecule hydrolyzed by myosin heads during isotonic
      shortening of skinned muscle fibers.
AB  - We measured isotonic sliding distance of single skinned fibers from rabbit psoas
      muscle when known and limited amounts of ATP were made available to the
      contractile apparatus. The fibers were immersed in paraffin oil at 20 degrees C,
      and laser pulse photolysis of caged ATP within the fiber initiated the
      contraction. The amount of ATP released was measured by photolyzing 3H-ATP within
      fibers, separating the reaction products by high-pressure liquid chromatography,
      and then counting the effluent peaks by liquid scintillation. The fiber stiffness
      was monitored to estimate the proportion of thick and thin filament sites
      interacting during filament sliding. The interaction distance, Di, defined as the
      sliding distance while a myosin head interacts with actin in the thin filament
      per ATP molecule hydrolyzed, was estimated from the shortening distance, the
      number of ATP molecules hydrolyzed by the myosin heads, and the stiffness. Di
      increased from 11 to 60 nm as the isotonic tension was reduced from 80% to 6% of
      the isometric tension. Velocity and Di increased with the concentration of ATP
      available. As isotonic load was increased, the interaction distance decreased
      linearly with decrease of the shortening velocity and extrapolated to 8 nm at
      zero velocity. Extrapolation of the relationship between Di and velocity to
      saturating ATP concentration suggests that Di reaches 100-190 nm at high
      shortening velocity. The interaction distance corresponds to the sliding distance
      while cross-bridges are producing positive (working) force plus the distance
      while they are dragging (producing negative forces). The results indicate that
      the working and drag distances increase as the velocity increases. Because Di is
      larger than the size of either the myosin head or the actin monomer, the results
      suggest that for each ATPase cycle, a myosin head interacts mechanically with
      several actin monomers either while working or while producing drag.

PMID- 8534821
TI  - The effect of genetically expressed cardiac titin fragments on in vitro actin
      motility.
AB  - Titin is a striated muscle-specific giant protein (M(r) approximately 3,000,000)
      that consists predominantly of two classes of approximately 100 amino acid
      motifs, class I and class II, that repeat along the molecule. Titin is found
      inside the sarcomere, in close proximity to both actin and myosin filaments.
      Several biochemical studies have found that titin interacts with myosin and
      actin. In the present work we investigated whether this biochemical interaction
      is functionally significant by studying the effect of titin on actomyosin
      interaction in an in vitro motility assay where fluorescently labeled actin
      filaments are sliding on top of a lawn of myosin molecules. We used genetically
      expressed titin fragments containing either a single class I motif (Ti I), a
      single class II motif (Ti II), or the two motifs linked together (Ti I-II).
      Neither Ti I nor Ti II alone affected actin-filament sliding on either myosin,
      heavy meromyosin, or myosin subfragment-1. In contrast, the linked fragment (Ti I
      II) strongly inhibited actin sliding. Ti I-II-induced inhibition was observed
      with full-length myosin, heavy meromyosin, and myosin subfragment-1. The degree
      of inhibition was largest with myosin subfragment-1, intermediate with heavy
      meromyosin, and smallest with myosin. In vitro binding assays and electrophoretic
      analyses revealed that the inhibition is most likely caused by interaction
      between the actin filament and the titin I-II fragment. The physiological
      relevance of the novel finding of motility inhibition by titin fragments is
      discussed.

PMID- 8534822
TI  - Dielectric response of triplex DNA in ionic solution from simulations.
AB  - We have analyzed a 1.2-ns molecular dynamics simulation of 51 mM d(CG.G)7 with 21
      Na+ counter-ions and 1 M NaCl in water. Via the dipole fluctuations, the
      dielectric constant for the DNA is found to be around 16, whereas that for the
      bases and sugars combined is only 3. The dielectric constant for water in this
      system is 41, which is much smaller than 71 for pure SPC/E water, because of the
      strong restriction imposed on the motion of water molecules by the DNA and the
      ions. Also addressed in the present work are several technical issues related to
      the calculation of the dipole moment of an ionic solution from molecular dynamics
      simulations using periodic boundary conditions.

PMID- 8534823
TI  - A free energy analysis of nucleic acid base stacking in aqueous solution.
AB  - This paper reports a theoretical study of the free energy contributions to
      nucleic acid base stacking in aqueous solution. Electrostatic interactions are
      treated by using the finite difference Poisson-Boltzmann method and nonpolar
      effects are treated with explicit calculation of van der Waals interactions
      and/or free energy-surface area relationships. Although for some pairs of bases
      there is a favorable Coulombic interaction in the stacked conformation, generally
      the net effect of electrostatic interactions is to oppose stacking. This result
      is caused by the loss of favorable base-solvent electrostatic interactions, that
      accompany the partial removal of polar atoms from water in the stacked
      conformation. Nonpolar interactions, involving the hydrophobic effect and
      enhancement of van der Waals interactions caused by close-packing, drive
      stacking. The calculations qualitatively reproduce the experimental dependence of
      stacking free energy on purine-pyrimidine composition.

PMID- 8534824
TI  - Nonlinear polarization spectroscopy in the frequency domain of light-harvesting
      complex II: absorption band substructure and exciton dynamics.
AB  - Spectral substructure and ultrafast excitation dynamics have been investigated in
      the chlorophyll (Chl) a and b Qy region of isolated plant light-harvesting
      complex II (LHC II). We demonstrate the feasibility of Nonlinear Polarization
      Spectroscopy in the frequency domain, a novel photosynthesis research laser
      spectroscopic technique, to determine not only ultrafast population relaxation
      (T1) and dephasing (T2) times, but also to reveal the complex spectral
      substructure in the Qy band as well as the mode(s) of absorption band broadening
      at room temperature (RT). The study gives further direct evidence for the
      existence of up to now hypothetical "Chl forms". Of particular interest is the
      differentiated participation of the Chl forms in energy transfer in trimeric and
      aggregated LHC II. Limits for T2 are given in the range of a few ten fs.
      Inhomogeneous broadening does not exceed the homogeneous widths of the subbands
      at RT. The implications of the results for the energy transfer mechanisms in the
      antenna are discussed.

PMID- 8534825
TI  - A mixed-ligand iron-sulfur cluster (C556SPaB or C565SPsaB) in the Fx-binding site
      leads to a decreased quantum efficiency of electron transfer in photosystem I.
AB  - The proposed structure of Photosystem I depicts two cysteines on the PsaA
      polypeptide and two cysteines on the PsaB polypeptide in a symmetrical
      environment, each providing ligands for the interpolypeptide Fx cluster. We
      studied the role of Fx in electron transfer by substituting serine for cysteine
      (C565SPsaB and C556SPsaB), thereby introducing the first example of a genetically
      engineered, mixed-ligand [4Fe-4S] cluster into a protein. Optical kinetic
      spectroscopy shows that after a single-turnover flash at 298 K, the contribution
      of A1- (lifetime of 10 microseconds, 40% of total and lifetime of 100
      microseconds, 20% of total) and Fx- (lifetime of 500-800 microseconds, 10-15% of
      total) to the overall P700+ back reaction have increased in C565SPsaB and
      C556SPsaB at the expense of the back reaction from [FA/FB]-. The electron
      paramagnetic resonance spectrum of Fx shows g-values of 2.04, 1.94, and 1.81 in
      both mutants and a similarly decreased amount of FA and FB reduced at 15 K after
      a single-turnover flash. These results indicate that the mixed-ligand (3
      cysteines, 1 serine) Fx cluster is an inefficient electron carrier, but that a
      small leak through Fx still permits FA and FB to be reduced quantitatively when
      the samples are frozen during continuous illumination. The data confirm that Fx
      is a necessary intermediate in the electron transfer pathway from A1 to FA and FB
      in Photosystem I.

PMID- 8534826
TI  - High-pressure near-infrared Raman spectroscopy of bacteriorhodopsin light to dark
      adaptation.
AB  - Near-infrared (NIR) Raman spectroscopy is employed as an in situ probe of the
      chromophore conformation to study the light to dark-adaptation process in
      bacteriorhodopsin (bR) at variable pressure and temperature in the absence of
      undesired photoreactions. In dark-adapted bR deconvolution of the ethylenic mode
      into bands assigned to the all-trans (1526 cm-1) and 13-cis (1534 cm-1) isomers
      yields a 13-cis to all-trans ratio equal to 1 at ambient pressure (Schulte et
      al., 1995, Appl. Spectrosc. 49:80-83). Detailed spectroscopic evidence is
      presented that at high pressure the equilibrium is shifted toward the 13-cis
      isomers and that the light to dark adaptation kinetics is accelerated. The change
      in isomeric composition with temperature and pressure as well as the kinetics
      support a two-state model activation volumes of -16 ml/mol for the transition of
      13-cis to all-trans and -22 ml/mol for the reverse process. These compare with a
      conformational volume difference of 6.6 ml/mol, which may be attributed to the
      ionization of one or two residues or the formation of three hydrogen bonds.

PMID- 8534827
TI  - The shapes of the motor domains of two oppositely directed microtubule motors,
      ncd and kinesin: a neutron scattering study.
AB  - The shapes of the motor domains of kinesin and ncd, which move in opposite
      directions along microtubules, have been investigated. Using proteins expressed
      in Escherichia coli, it was found that at high salt (> 200 mM) Drosophila ncd
      motor domain (R335-K700) and human kinesin motor domain (M1-E349) were both
      sufficiently monomeric to allow an accurate determination of their radii of
      gyration (Rg) and their molecular weights. The measured Rg values of the ncd and
      kinesin motor domains in D2O were 2.06 +/- 0.06 and 2.05 +/- 0.04 nm,
      respectively, and the molecular weights were consistent with those computed from
      the amino acid compositions. Fitting of the scattering curves to approximately
      3.5 nm resolution showed that the ncd and kinesin motor domains can be described
      adequately by triaxial ellipsoids having half-axes of 1.42 +/- 0.38, 2.24 +/-
      0.44, and 3.65 +/- 0.22 nm, and half-axes of 1.52 +/- 0.23, 2.00 +/- 0.25, and
      3.73 +/- 0.10 nm, respectively. Both motor domains are described adequately as
      somewhat flattened prolate ellipsoids with a maximum dimension of approximately
      7.5 nm. Thus, it appears that the overall shapes of these motor domains are not
      the major determinants of the directionality of their movement along
      microtubules.

PMID- 8534828
TI  - Theory and application of fluorescence homotransfer to melittin oligomerization.
AB  - Fluorescence homotransfer (electronic energy transfer between identical
      fluorophores) has the potential to quantitate the number of subunits in membrane
      protein oligomers. Homotransfer strongly depolarizes fluorescence emission as a
      result of intermolecular excitation energy exchange between an initially excited,
      oriented molecule and a randomly oriented neighbor. We have theoretically treated
      fluorescein labeled subunits in an oligomer as a cluster of molecules that can
      exchange excitation energy back and forth among the subunits within that group.
      We find that the larger the number of subunits, the more depolarized is the
      emission. The general equations to calculate the expected anisotropy for
      complexes composed of varying numbers of labeled subunits are presented. Self
      quenching of fluorophores, orientation, and changes in lifetime are also
      discussed and/or considered. To test this theory, we have specifically labeled
      melittin on its N-terminal with fluorescein and monitored its monomer to tetramer
      equilibrium both in solution and in lipid bilayers. The calculated anisotropies
      are close to the experimental values when non-fluorescent fluorescein dimers are
      taken into account. Our results show that homotransfer may be a promising method
      to study membrane-protein oligomerization.

PMID- 8534829
TI  - Physical and chemical effects of red cells in the shear-induced aggregation of
      human platelets.
AB  - Both chemical and physical effects of red cells have been implicated in the
      spontaneous aggregation of platelets in sheared whole blood (WB). To determine
      whether the chemical effect is due to ADP leaking from the red cells, a
      previously described technique for measuring the concentration and size of single
      platelets and aggregates was used to study the shear-induced aggregation of
      platelets in WB flowing through 1.19-mm-diameter polyethylene tubing in the
      presence and absence of the ADP scavenger enzyme system phosphocreatine-creatine
      phosphokinase (CP-CPK). Significant spontaneous aggregation was observed at mean
      tube shear rates, (G) = 41.9 and 335 s-1 (42% and 13% decrease in single
      platelets after a mean transit time (t) = 43 s, compared to 89 and 95% decrease
      with 0.2 microM ADP). The addition of CP-CPK, either at the time of, or 30 min
      before each run, completely abolished aggregation. In the presence of 0.2 microM
      ADP, CP-CPK caused a reversal of aggregation at (t) = 17 s after 30% of single
      cells had aggregated. To determine whether red cells exert a physical effect by
      increasing the time of interaction of two colliding platelets (thereby increasing
      the proportion of collisions resulting in the formation of aggregates), an
      optically transparent suspension of 40% reconstituted red cell ghosts in serum
      containing 2.5-micron-diameter latex spheres (3 x 10(5)/microliters) flowing
      through 100-microns-diameter tubes was used as a model of platelets in blood, and
      the results were compared with those obtained in a control suspension of latex
      spheres in serum alone. Two-body collisions between microspheres in the interior
      of the flowing ghost cell or serum suspensions at shear rates from 5 to 90 s-1
      were recorded on cine film. The films were subsequently analyzed, and the
      measured doublet lifetime, tau meas, was compared with that predicted by theory
      in the absence of interactions with other particles, tau theor. The mean (tau
      meas/tau theor) for doublets in ghost cell suspensions was 1.614 +/- 1.795 (SD; n
      = 320), compared to a value of 1.001 +/- 0.312 (n = 90) for doublets in serum.
      Whereas 11% of doublets in ghost cell suspensions had lifetimes from 2.5 to 5
      times greater than predicted, in serum, no doublets had lifetimes greater than
      1.91 times that predicted. There was no statistically significant correlation
      between tau meas/tau theor and shear rate, but the values of tau meas/tau theor
      for low-angle collisions in ghost cell suspensions were significantly greater
      than for high-angle collisions.

PMID- 8534830
TI  - Anaphase chromatid motion: involvement of type II DNA topoisomerases.
AB  - Sister chromatids are topologically intertwined at the onset of anaphase: their
      segregation during anaphase is known to require strand-passing activity by type
      II DNA topoisomerase. We propose that the removal of the intertwinings involves
      at the same time the traction of the mitotic spindle and the activity of
      topoisomerases. This implies that the velocity of the chromatids is compatible
      with the kinetic constraints imposed by the enzymatic reaction. We show that the
      greatest observed velocities (about 0.1 microns s-1) are close to the theoretical
      upper bound compatible with both the diffusion rate (calculated here within a
      probabilistic model) and the measured reaction rate of the enzyme.

PMID- 8534831
TI  - GnRH-induced cytosolic calcium oscillations in pituitary gonadotrophs: phase
      resetting by membrane depolarization.
AB  - Cultured rat pituitary gonadotrophs under whole-cell voltage clamp conditions
      respond to the hypothalamic hormone GnRH with synchronized oscillatory changes in
      both cytosolic Ca2+ concentration ([Ca2+]i) and [Ca2+]i-activated, apamin
      sensitive K+ current (IK(Ca)). We found, and report here for the first time, that
      in GnRH-stimulated cells a brief depolarizing pulse can elicit a transient
      [Ca2+]i rise similar to the endogenous cycle. Furthermore, Ca2+ entry during a
      single depolarizing pulse was found to shift the phase of subsequent endogenous
      [Ca2+]i oscillations, which thereafter continue to occur at their previous
      frequency before the pulse. Application of two consecutive depolarizing pulses
      showed that the size of the [Ca2+]i rise evoked by the second pulse depended on
      the time lapsed between two consecutive pulses, indicating that each endogenous
      or evoked [Ca2+]i rise cycle leaves the Ca2+ release mechanism of the gonadotroph
      in a refractory state. Recovery from this condition can be described by an
      exponential function of the time lapsed between the pulses (time constant of ca.
      1 s). We propose that the underlying mechanism in both refractoriness after
      endogenous cycles and phase resetting by a brief pulse of Ca2+ entry involves the
      InsP3 receptor-channel molecule presumed to be located on the cytosolic aspect of
      the endoplasmic reticulum membrane.

PMID- 8534832
TI  - Photoelectron imaging of cells: photoconductivity extends the range of
      applicability.
AB  - Photoelectron imaging is a sensitive surface technique in which photons are used
      to excite electron emission. This novel method has been applied successfully in
      studies of relatively flat cultured cells, viruses, and protein-DNA complexes.
      However, rounded-up cell types such as tumor cells frequently are more difficult
      to image. By comparing photoelectron images of uncoated and metal-coated MCF-7
      human breast carcinoma cells, it is shown that the problem is specimen charging
      rather than a fundamental limitation of the electron imaging process. This is
      confirmed by emission current measurements on uncoated monolayers of MCF-7
      carcinoma cells and flatter, normal Wi-38 fibroblasts. We report here that sample
      charging in photoelectron microscopy can be eliminated in most specimens by
      simultaneous use of two light sources--the standard UV excitation source (e.g.,
      254 nm) and a longer wavelength light source (e.g., 325 nm). The reduction in
      sample charging results largely from enhanced photoconduction in the bulk sample
      and greatly extends the range of cells that can be examined by photoelectron
      imaging. The contributions of photoconductivity, the electric field of the
      imaging system, and the short escape depths of the photoelectrons combine to make
      photoelectron imaging a uniquely sensitive technique for the study of biological
      surfaces.

PMID- 8534833
TI  - Thermodynamic nonideality of enzyme solutions supplemented with inert solutes:
      yeast hexokinase revisited.
AB  - Published experimental results on the activating effect of polyethylene glycol on
      the interaction of yeast hexokinase with glucose (R.P. Rand, N.L. Fuller, P.
      Butko, G. Francis and P. Nicholls, Biochemistry, 32 (1993) 5925) are
      reinterpreted in statistical-mechanical terms of excluded volume. Of particular
      interest is the ability of this standard treatment of thermodynamic nonideality
      to accommodate the observed non-exponential dependence of the activation upon
      osmotic pressure of the polyethylene glycol solution--a dependence which is not
      predicted by analyses based on the concept of osmotic stress that was invoked
      originally to account for the results.

PMID- 8534834
TI  - Watching molecules crowd: DNA double helices under osmotic stress.
AB  - Simultaneous measurements on the packing and energetics of high-density liquid
      crystalline DNA phases show that the crowding of long DNA polyelectrolytes at
      ever increasing concentrations is accomplished through straightening of the
      random coils that the double helix assumes in dilute solution. X-ray scattering
      by ordered phases reveals that the local straightening of the molecules is also
      accompanied by their progressive immobilization and confinement within the
      molecular 'cages' created by neighboring molecules. These effects can be clearly
      observed through the measured energies of DNA packing under osmotic stress and
      through the changes in structural and dynamic characteristics of X-ray scattering
      from DNA in ordered arrays at different concentrations. The character of the
      confinement of large DNA motions for a wide range of DNA concentrations is
      dominated by the soft potentials of direct interaction. We do not see the power
      law variation of energy vs. volume expected from space-filling fluctuations of
      molecules that enjoy no interaction except the hard clash of steric repulsion.
      Rather, in highly concentrated DNA mesophases we see a crowding of molecules
      through electrostatic or hydration repulsion that confines their movements and
      positions. This view is based on directly measured packing energies as well as on
      concurrently measured structural parameters while the DNA double helices are
      condensed under an externally applied osmotic pressure.

PMID- 8534835
TI  - Effects of dextran on the self-association of human spectrin.
AB  - The self-association of human spectrin is enhanced in the presence of dextran.
      The equilibrium constant for association of two heterodimers to form a tetramer
      is increased by an order of magnitude in the presence of 20% dextran. The rate
      constant for association is also enhanced, while the rate constant for
      dissociation is almost independent of dextran concentration. The degree of
      enhancement of association is dependent only on the mass concentration of
      dextran; for a given mass concentration of dextran the effect is independent of
      dextran molecular weight. These effects are believed to be due to excluded volume
      phenomena, and a model is presented that realistically accounts for the effects.
      These results imply that the association of spectrin within the erythrocyte will
      be enhanced by the presence of hemoglobin.

PMID- 8534836
TI  - Stabilizing effect of sucrose against irreversible denaturation of rabbit muscle
      lactate dehydrogenase.
AB  - Measurements of the kinetics of activity loss by rabbit muscle lactate
      dehydrogenase in acetate-chloride buffer, pH 5.0, I 0.20, have shown that the
      enzyme exhibits greater stability against irreversible inactivation when the
      buffer is supplemented with sucrose (0.1 M-0.5 M). On the basis of sedimentation
      equilibrium distributions obtained for enzyme in the absence and presence of
      sucrose (0.5 M), the lactate dehydrogenase is essentially dimeric in both
      environments. The observed stabilization of enzyme activity has therefore been
      considered in terms of the space-filling effects of sucrose on an isomerization
      equilibrium between native and unfolded forms of dimeric lactate dehydrogenase,
      which precedes irreversible inactivation of the unfolded isomer. Interpretation
      of the kinetic results on that basis has led to the conclusion that the initial
      stage of enzyme unfolding entails a minor change in volume and/or asymmetry of
      the lactate dehydrogenase that gives rise to a 4% increase in the second virial
      coefficient describing excluded volume interactions between dimeric enzyme and
      sucrose.

PMID- 8534837
TI  - A molecular model for the dependence of the osmotic pressure of bovine serum
      albumin upon concentration and pH.
AB  - Expressions derived from the effective hard particle model of Minton and Edelhoch
      (Biopolymers, 21 (1982) 451) account quantitatively for the combined data of
      Kanal et al. (Biophys. J., 66 (1994) 153) describing the osmotic pressure of
      bovine serum albumin as a function of protein concentration (< or = ca. 100
      milligrams) and pH (3-8) in buffered 0.1 M NaCl. The best fit of the model yields
      a molar mass of 68360 and a pH-dependent value of the effective specific volume
      ranging from a minimum of -0.17 cm3/g at pH 4.6 (the isoelectric point) to maxima
      of 3.1 cm3/g at pH 3.0 and 2.2 cm3/g at pH 8.0. These values are shown to be
      consistent with the magnitude of known attractive and repulsive electrostatic
      interactions between proteins in solution.

PMID- 8534838
TI  - Condensation and cohesion of lambda DNA in cell extracts and other media:
      implications for the structure and function of DNA in prokaryotes.
AB  - DNA added to concentrated extracts of Escherichia coli undergoes a reversible
      transition to a readily-sedimentable ('condensed') form. The transition occurs
      over a relatively small increment in extract concentration. The extract appears
      to play two roles in this transition, supplying both DNA-binding protein(s) and a
      crowded environment that increases protein binding and favors compact DNA
      conformations. The two roles of the extract are suggested by properties of
      fractions prepared by absorption of extracts with DNA-cellulose. The DNA-binding
      fraction and the DNA-nonbinding fractions from these columns are separately
      poorer condensing agents than the original extract, but when rejoined are similar
      to the original extract in the amount required for condensation. The dual role
      for the extract is supported by model studies of condensation with combinations
      of purified DNA-binding materials (protein HU or spermidine) and concentrated
      solutions of crowding agents (albumin or polyethylene glycol 8000); in each case,
      crowding agents and DNA-binding materials jointly reduce the amounts of each
      other required for condensation. The condensation reaction as studied in extracts
      or in the purified systems may be a useful approach to the forces which stabilize
      the compact form of DNA within the bacterial nucleoid. The effect of condensation
      on the reactivity of the DNA was measured by changes in the rate of cohesion
      between duplex DNA molecules bearing the complementary single-strand termini of
      lambda DNA. Condensation caused large increases in the rates of cohesion of both
      lambda DNA and of restriction fragments of lambda DNA bearing the cohesive
      termini. Cohesion products of lambda DNA made in vitro are a mixture of linear
      and circular aggregates, whereas those made in vivo are cyclic monomers. We
      suggest a simple mechanism based upon condensation at the site of viral injection
      which may explain this discrepancy.

PMID- 8534839
TI  - Crowding-induced organization of cytoskeletal elements. III. Spontaneous bundling
      and sorting of self-assembled filaments with different flexibilities.
AB  - The typical cell contains ca. 25 vol.-% protein, of which ca. 10% forms
      cytoskeletal filaments and ca. 90% is non-aggregating globular protein. It has
      previously been theoretically predicted that, under such highly crowded
      conditions, rigid filaments will coalesce into tight bundles coexisting with an
      isotropic solution of globular proteins. In the present work we show that such
      spontaneous bundling will occur even when filament flexibility is taken into
      account because the persistence length of the filaments is much longer than the
      diameter of the globular proteins. The theoretical results are consistent with
      experimentally observed bundling of F-actin (the most flexible of the three most
      common types of cytoskeletal filaments) in the presence of globular
      macromolecules.The main effect of increased filament flexibility on bundling is
      to cause somewhat looser packing. In mixtures of filaments, differences in
      flexibilities can lead to segregation. This segregation is accentuated when the
      stiffer filament is also wider. The results suggest that actin filaments and
      microtubules will spontaneously form segregated bundles in the presence of
      cellular concentrations of globular proteins. While cross-linking proteins may
      serve to stabilize these bundles, their more important function in bundling may
      be to fine tune the structure (e.g., polarity and registration of filaments).

PMID- 8534840
TI  - 34th Annual Scientific Meeting of the British Society for Clinical Cytology.
      Dundee, United Kingdom, 17-20 September 1995. Abstracts.

PMID- 8534841
TI  - Achievable standards, benchmarks for reporting, criteria for evaluating cervical
      cytopathology. Workshop report.

PMID- 8534842
TI  - Promoter analysis of the auxin-regulated tobacco glutathione S-transferase genes
      Nt103-1 and Nt103-35.
AB  - We have analysed the promoter regions of two closely related auxin-regulated
      glutathione S-transferase genes. All active deletion constructs tested showed
      expression of the reporter gene beta-glucuronidase (gusA) in root tips of young
      seedlings and newly developing lateral roots. Auxin treatment greatly enhanced
      the level of expression. The Nt103-1 promoter region -370/-276 was found to be
      necessary, at least as a quantitative element to confer auxin-responsiveness to a
      reporter gene, and sequences responsible for the auxin-responsiveness must be
      located downstream of -370. The region -651/-370 contains sequence information
      necessary for uninduced expression. The Nt103-35 promoter manifested its auxin
      responsiveness within the -504/-310 region. Electrophoretic mobility shift
      analysis, using nuclear extracts from tobacco leaves and suspension cells,
      identified a factor binding to a sequence (ap103, TGAGTCT) at position -560 of
      the Nt103-1 promoter, which shows homology to the mammalian AP-1 site. A second
      factor was found to bind a sequence (as103, ATAGCTAAGTGCTTACG) with homology to
      the CaMV 35S promoter as-1 element. The as103 element is present in both
      promoters and positioned around -360, so within the region determined to be
      indispensable for the response to auxin. A third factor was found binding to the 
      276/-190 region of both promoters. Combined, these data point to the relevance of
      a 90 bp region for auxin-induced activity of both tobacco genes. The ASF-1 like
      factor binding to the as103 element within this region might be involved in
      mediating the auxin response.

PMID- 8534843
TI  - Sugar-binding activity of pea (Pisum sativum) lectin is essential for
      heterologous infection of transgenic white clover hairy roots by Rhizobium
      leguminosarum biovar viciae.
AB  - Legume lectin stimulates infection of roots in the symbiosis between leguminous
      plants and bacteria of the genus Rhizobium. Introduction of the Pisum sativum
      lectin gene (psl) into white clover hairy roots enables heterologous infection
      and nodulation by the pea symbiont R. leguminosarum biovar viciae (R.l. viciae).
      Legume lectins contain a specific sugar-binding site. Here, we show that
      inoculation of white clover hairy roots co-transformed with a psl mutant encoding
      a non-sugar-binding lectin (PSL N125D) with R.l. viciae yielded only background
      pseudo-nodule formation, in contrast to the situation after transformation with
      wild type psl or with a psl mutant encoding sugar-binding PSL (PSL A126V). For
      every construct tested, nodulation by the homologous symbiont R.l. trifolii was
      normal. These results strongly suggest that (1) sugar-binding activity of PSL is
      necessary for infection of white clover hairy roots by R.l. viciae, and (2) the
      rhizobial ligand of host lectin is a sugar residue rather than a lipid.

PMID- 8534844
TI  - Athila, a new retroelement from Arabidopsis thaliana.
AB  - An analysis of Arabidopsis thaliana heterochromatic regions allowed the
      identification of a new family of retroelements called Athila. These 10.5 kb
      elements, representing ca. 0.3% of the genome, present several features of
      retrotransposons and retroviruses. Athila elements are flanked by 1.5 kb long
      terminal repeats (LTR) that are themselves bounded by 5 bp perfect inverted
      repeats. These LTRs start and end with the retroviral consensus 5'TG...CA3'
      nucleotides. A putative tRNA-binding site and a polypurine tract are found
      adjacent to the 5' and 3' LTR respectively. The central domain is composed of two
      long open reading frames (ORFs) of 935 and 694 amino acids. Despite several
      indications of recent transposition activity, the translation of these ORFs
      failed to reveal significant homology with proteins associated to
      retrotransposition. We suggest that the Athila family could result from the
      transduction and dispersion of a cellular gene by a retrotransposon.

PMID- 8534845
TI  - Isolation, chemical structures and biological activity of the lipo-chitin
      oligosaccharide nodulation signals from Rhizobium etli.
AB  - Rhizobium etli is a microsymbiont of plants of the genus Phaseolus. Using mass
      spectrometry we have identified the lipo-chitin oligosaccharides (LCOs) that are
      produced by R. etli strain CE3. They are N-acetylglucosamine pentasaccharides of
      which the non-reducing residue is N-methylated and N-acylated with cis-vaccenic
      acid (C18:1) or stearic acid (C18:0) and carries a carbamoyl group at C4. The
      reducing residue is substituted at the C6 position with O-acetylfucose. Analysis
      of their biological activity on the host plant Phaseolus vulgaris shows that
      these LCOs can elicit the formation of nodule primordia which develop to the
      stage where vascular bundles are formed. The formation of complete nodule
      structures, including an organized vascular tissue, is never observed.
      Considering the very close resemblance of the R. etli LCO structures to those of
      R. loti (I. M. Lopez-Lara, J. D. J. van den Berg, J. E. Thomas Oates, J. Glushka,
      B. J. J. Lugtenberg, H. P. Spaink, Mol Microbiol 15: 627-638, 1995) we tested the
      ability of R. etli strains to nodulate various Lotus species and of R. loti to
      nodulate P. vulgaris. The results show that R. etli is indeed able to nodulate
      Lotus plants. However, several Lotus species are only nodulated when an
      additional flavonoid independent transcription activator (FITA) nodD gene is
      provided. Phaseolus plants can also be nodulated by R. loti bacteria, but only
      when the bacteria contain a FITA nodD gene. Apparently, the type of nod gene
      inducers secreted by the plants is the major basis for the separation of
      Phaseolus and Lotus into different cross inoculation groups.

PMID- 8534846
TI  - Induction of nodule primordia on Phaseolus and Acacia by lipo-chitin
      oligosaccharide nodulation signals from broad-host-range Rhizobium strain GRH2.
AB  - Rhizobium wild-type strain GRH2 was originally isolated from the tree, Acacia
      cyanophylla, and has a broad host-range which includes herbaceous legumes, such
      as Phaseolus and Trifolium species. Here we show that strains of Rhizobium sp.
      GRH2, into which heterologous nodD alleles have been introduced, produce a large
      diversity of both sulphated and non-sulphated lipo-chitin oligosaccharides
      (LCOs). Most of the molecular species contain an N-methyl group on the reducing
      terminal N-acetyl-glucosamine. The LCOs vary in the nature of the fatty acyl
      chain and in the length of the chitin backbone. The majority of the LCOs have an
      oligosaccharide chain length of five GlcNAc residues, but a few are oligomers
      having six GlcNAc units. LCOs purified from GRH2 are able to induce root hair
      formation and deformation on Acacia cyanophylla and A. melanoxylon plants. We
      show that an N-vaccenoyl-chitopentaose bearing an N-methyl group is able to
      induce nodule primordia on Phaseolus vulgaris, A. cyanophylla, and A.
      melanoxylon, indicating that for these plants an N-methyl modification is
      sufficient for nodule primordia induction.

PMID- 8534847
TI  - Expression of Arabidopsis cytosolic ascorbate peroxidase gene in response to
      ozone or sulfur dioxide.
AB  - The effects of ozone or sulfur dioxide on antioxidant enzymes were investigated
      in Arabidopsis thaliana. Plants were fumigated with 0.1-0.15 ppm ozone or sulfur
      dioxide up to about 1 week in an environment-controlled chamber. Both pollutants
      increased the activities of ascorbate peroxidase and guaiacol peroxidase in
      leaves, but had little effect on the activities of superoxide dismutase,
      catalase, monodehydroascorbate reductase, dehydroascorbate reductase or
      glutathione reductase. Ozone was more effective than sulfur dioxide in increasing
      the activities of the peroxidases. Ascorbate peroxidase activity increased 1.8
      fold without a lag period during fumigation with 0.1 ppm ozone, while guaiacol
      peroxidase activity increased 4.4-fold with a 1-day lag. Expression of the APX1
      gene encoding cytosolic ascorbate peroxidase was further investigated. Its
      protein levels in leaves exposed to 0.1 ppm ozone for 4 or 8 days were 1.5-fold
      higher than in controls. Both ozone and sulfur dioxide elevated APX1 mRNA levels
      in leaves at 4 and 7 days, whereas at 1 day only ozone was effective. The
      induction of APX1 mRNA levels by ozone (3.4- to 4.1-fold) was more prominent than
      that by sulfur dioxide (1.6- to 2.6-fold). The APX1 mRNA level increased by day
      and decreased by night. Exposure of plants to 0.1 ppm ozone enhanced the APX1
      mRNA level within 3 h, which showed a diurnal rhythm similar to that of the
      control. These results demonstrate that near-ambient concentrations of ozone as
      well as similar concentrations of sulfur dioxide can induce APX1 gene expression
      in A. thaliana.

PMID- 8534848
TI  - Identification of cDNA clones corresponding to two inducible nitrate reductase
      genes in soybean: analysis in wild-type and nr1 mutant.
AB  - Among higher plants, soybean is unique in that biochemically it has been
      characterized as having two constitutive nitrate reductase (cNR) isoforms and one
      substrate-inducible nitrate reductase (iNR) isoform in leaves. All three NR
      isoforms are expressed in cv. Williams 82 while the nr1 mutant expresses only the
      iNR isoform. The genetic and molecular mechanisms for regulation of these
      isoforms have not been elucidated. We describe here the isolation, by reverse
      transcription-polymerase chain reaction (RT-PCR), of two cDNA clones encoding
      soybean NR. They were designated as iNR1 and iNR2, respectively, since both were
      inducible by nitrate. The iNR1 and iNR2 cDNAs cover total encoding regions of
      2661 and 2673 nucleotides, respectively. The iNR1 clone shows a 12 bp deletion at
      the 5' end, relative to iNR2. They show overall similarity of 89% at the
      nucleotide level, and 87% at the amino acid level. Like all plant NRs cloned so
      far, deduced amino acid sequences between iNR1 and iNR2 show greatest variation
      at the N-terminal region while no difference was observed at the C-terminus.
      Soybean iNR mRNAs were found to be different from those of maize and tobacco in
      response to tungsten inhibitor treatment, since the inhibitor decreased the
      steady-state levels of mRNA for soybean iNR and for NiR. Using the same 5'
      regions of both cDNAs as the probes, Southern blot analysis of genomic DNA
      revealed differences in organization between iNR1 and iNR2. The genomic DNA from
      wild-type Williams 82 soybean was shown to have three Eco RI fragments while the
      nr1 mutant lacked an 8 kb fragment when probed with iNR1 cDNA. Likewise, the nr1
      mutant lacked three Hae III restriction fragments when probed with iNR1 cDNA.
      When probed with iNR2, both wildtype and nr1 mutant showed one identical Eco RI
      band and two identical Hae III bands. In northern blots, the steady-state level
      of iNR1 mRNA was similar for the nr1 mutant and the wild-type parent after 20 to
      48 h induction by nitrate. Based on the Eco RI and Hae III restriction enzyme
      digestion patterns observed in Southern blot analysis of soybean DNA, it is
      concluded that in soybean iNR1 is encoded by a small multiple gene family and
      iNR2 is a single gene.

PMID- 8534849
TI  - Sequence and expression characteristics of three G-box-binding factor cDNAs from
      Brassica napus [corrected].
AB  - G-box-binding factors (GBFs) are bZIP proteins that have been implicated in the
      transcriptional control of a number of plant genes including the family for the
      small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. Using rbcS
      promoter regions as recognition site probes, we have cloned three Brassica GBFs
      designated as BnGBF1a, 1b and 2a. RNA gel blot analyses showed that all three
      BnGBF sequences give transcripts of the same size (1.3 kb) but in different
      amounts at a constant ratio in various tissues and developmental stages (1a > 2a
      > 1b). Transcript pools were largest in photosynthetically active organs such as
      leaves and cotyledons. Pool sizes correlated with those of total rbcS
      transcripts.

PMID- 8534850
TI  - Functional analysis of a recently originating, atypical presequence:
      mitochondrial import and processing of GUS fusion proteins in transgenic tobacco
      and yeast.
AB  - A gene family of at least five members encodes the tobacco mitochondrial Rieske
      Fe-S protein (RISP). To determine whether all five RISPs are translocated to
      mitochondria, fusion proteins containing the putative presequences of tobacco
      RISPs and Escherichia coli beta-glucuronidase (GUS) were expressed in transgenic
      tobacco, and the resultant GUS proteins were localized by cell fractionation. The
      amino-terminal 75 and 71 residues of RISP2 and RISP3, respectively, directed GUS
      import into mitochondria, where fusion protein processing occurred. The amino
      terminal sequence of RISP4, which contains an atypical mitochondrial presequence,
      can translocate the GUS protein specifically into tobacco mitochondria with
      apparently low efficiency. Consistent with the proposal of a conserved mechanism
      for protein import in plants and fungi, the tobacco RISP3 and RISP4 presequences
      can direct import and processing of a GUS fusion protein in yeast mitochondria.
      Plant presequences, however, direct mitochondrial import in yeast less
      efficiently than the yeast presequence, indicating subtle differences between the
      plant and yeast mitochondrial import machineries. Our studies show that import of
      RISP4 may not require positively charged amino acid residues and an amphipathic
      secondary structure; however, these structural properties may improve the
      efficiency of mitochondrial import.

PMID- 8534851
TI  - Cloning and properties of a rice gene encoding phenylalanine ammonia-lyase.
AB  - Phenylalanine ammonia-lyase (PAL) genomic sequences were isolated from a rice
      (Oryza sativa L.) genomic library using a PCR-amplified rice PAL DNA fragment as
      a probe. There is a small family of PAL genes in the rice genome. The nucleotide
      sequence of one PAL gene, ZB8, was determined. The ZB8 gene is 4660 bp in length
      and consists of two exons and one intron. It encodes a polypeptide of 710 amino
      acids. The transcription start site was 137 bp upstream from the translation
      initiation site. Rice PAL transcripts accumulated to a high level in stems, with
      lower levels in roots and leaves. Wounding of leaf tissues induced ZB8 PAL
      transcripts to a high level. In rice suspension-cultured cells treated with
      fungal cell wall elicitors, the ZB8 PAL transcript increased within 30 min and
      reached maximum levels in 1-2 h. The transcription of the ZB8 gene was
      investigated by fusing its promoter to the reporter gene beta-glucuronidase (GUS)
      and transforming the construct into rice and tobacco plants, as well as rice
      suspension-cultured cells. High levels of GUS activity were observed in stems,
      moderate levels in roots and low levels in leaves of transgenic rice and tobacco
      plants. Histochemical analysis indicated that in transgenic rice the promoter was
      active in root apical tips, lateral root initiation sites, and vascular and
      epidermal tissues of stems and roots. In rice flowers, high GUS activity was
      observed in floral shoots, receptacles, anthers and filaments, occasionally GUS
      activity was also detected in lemma and awn tissues. In tobacco flowers, high GUS
      activity was detected in the pink part of petals. Consistent with the activity of
      endogenous PAL transcripts, wounding of rice and tobacco leaf tissues induced GUS
      activity from low basal levels. Tobacco mosaic virus (TMV) infection of tobacco
      leaves induced GUS activity to a high level. Fungal cell wall elicitors strongly
      induced GUS activity and GUS transcripts to high levels in transgenic rice
      suspension-cultured cells. We demonstrated that the promoter of ZB8 gene is both
      developmentally regulated and stress-inducible.

PMID- 8534852
TI  - Differential accumulation of the transcripts of 22 novel protein kinase genes in
      Arabidopsis thaliana.
AB  - 22 novel members of the Arabidopsis thaliana protein kinase family (AKs) were
      identified by using degenerate oligonucleotide primers directed to highly
      conserved amino acid sequences of the protein kinase (PK) catalytic domain. Of
      these 22 genes, 16 turned out to carry intron sequences. Homologies of AK
      sequences were detected to S-locus receptor protein kinases (SRKs) from Brassica
      spp., to SRK-like PKs from maize and A. thaliana and to several other receptor
      PKs from A. thaliana. Sequence similarity was also detected to Ca(2+)-dependent
      PKs (CDPKs) from rape and soybean, to SNF1 and to CDC2 homologues. The genomic
      organization and the accumulation of the mRNAs from these 22 AK genes were
      investigated.

PMID- 8534853
TI  - Novel aspects of the regulation of a cDNA (Arf1) from Chlamydomonas with high
      sequence identity to animal ADP-ribosylation factor 1.
AB  - ADP-ribosylation factor (ARF) is a highly conserved, low molecular mass (ca. 21
      kDa) GTP-binding protein that has been implicated in vesicle trafficking and
      signal transduction in yeast and mammalian cells. However, little is known of ARF
      in plant systems. A putative ARF polypeptide was identified in subcellular
      fractions of the green alga Chlamydomonas reinhardtii, based on [32P]GTP binding
      and immunoblot assays. A cDNA clone was isolated from Chlamydomonas (Arf1), which
      encodes a 20.7 kDa protein with 90% identity to human ARF1. Northern blot
      analyses showed that levels of Arf1 mRNA are highly regulated during 12 h/12 h
      light/dark (LD) cycles. A biphasic pattern of expression was observed: a
      transient peak of Arf1 mRNA occurred at the onset of the light period, which was
      followed ca. 12 h later by a more prominent peak in the early to mid-dark period.
      When LD-synchronized cells were shifted to continuous darkness, the dark-specific
      peak of Arf1 mRNA persisted, indicative of a circadian rhythm. The increase in
      Arf1 mRNA at the beginning of the light period, however, was shown to be light
      dependent, and, moreover, dependent on photosynthesis, since it was prevented by
      DCMU. We conclude that the biphasic pattern of Arf1 mRNA accumulation during LD
      cycles is due to regulation by two different factors, light (which requires
      photosynthesis) and the circadian clock. Thus, these studies identify a novel
      pattern of expression for a GTP-binding protein gene.

PMID- 8534854
TI  - A lectin and a lectin-related protein are the two most prominent proteins in the
      bark of yellow wood (Cladrastis lutea).
AB  - Using a combination of cDNA cloning and protein purification it is demonstrated
      that bark of yellow wood (Cladrastis lutea) contains two mannose/glucose binding
      lectins and a lectin-related protein which is devoid of agglutination activity.
      One of the lectins (CLAI) is the most prominent bark protein. It is built up of
      four 32 kDa monomers which are post-translationally cleaved into a 15 kDa and a
      17 kDa polypeptide. The second lectin (CLAII) is a minor protein, which strongly
      resembles CLAI except that its monomers are not cleaved into smaller
      polypeptides. Molecular cloning of the Cladrastis lectin family revealed also the
      occurrence of a lectin-related protein (CLLRP) which is the second most prominent
      bark protein. Although CLLRP shows sequence homology to the true lectins, it is
      devoid of carbohydrate binding activity. Molecular modelling of the three
      Cladrastis proteins has shown that their three-dimensional structure is strongly
      related to the three-dimensional models of other legume lectins and, in addition,
      revealed that the presumed carbohydrate binding site of CLLRP is disrupted by an
      insertion of three extra amino acids. Since it is demonstrated for the first time
      that a lectin and a non-carbohydrate binding lectin-related protein are the two
      most prominent proteins in the bark of a tree, the biological meaning of their
      simultaneous occurrence is discussed.

PMID- 8534855
TI  - Tissue-specific and light-responsive regulation of the promoter region of the
      Arabidopsis thaliana chloroplast omega-3 fatty acid desaturase gene (FAD7).
AB  - The Arabidopsis FAD7 gene encodes a chloroplast omega-3 fatty acid desaturase
      that catalyzes the desaturation of lipid-linked dienoic fatty acids (18:2 and
      16:2). An 825 bp FAD7 promoter fragment upstream from the transcriptional start
      point contained several short sequences which were homologous to the cis-elements
      (box II, G-box, etc.) conserved in many light-responsive genes. We introduced the
      FAD7 promoter fused to the beta-glucuronidase (GUS) or the luciferase (LUC)
      reporter gene into tobacco plants. The -825 promoter sequence conferred tissue
      specific and light-responsive expression to both these reporter genes in
      transgenic tobacco, indicating that these expressions of the FAD7 gene were
      regulated mainly at the transcriptional level. Histochemical GUS staining showed
      that the activity of the FAD7 promoter is restricted to the tissues with
      chloroplast-containing cells although the staining was noticeably absent in the
      chloroplast-containing cells associated with vascular systems. The 5' deletion
      experiments of the promoter revealed that the -362/-166 region, containing two
      putative box II sequences, was responsible for the tissue-specific and light
      responsive expression of the FAD7 gene.

PMID- 8534856
TI  - Molecular cloning, characterization and expression of an elongation factor 1
      alpha gene in maize.
AB  - A cDNA (zmEF1A) and the corresponding genomic clone (zmgEF1A) of a member of the
      gene family encoding the alpha subunit of translation elongation factor 1 (EF-1
      alpha) have been isolated from maize. The deduced amino acid sequence is 447
      residues long interrupted by one intron. Southern blot analysis reveals that the
      cloned EF-1 alpha gene is one member out of a family consisting of at least six
      genes. As shown by northern hybridizations in leaves the mRNA level increases at
      low temperature whereas time-course experiments over 24 h at 5 degrees C show
      that in roots the overall mRNA level of EF-1 alpha is transiently decreased.
      These results indicate that the expression of EF-1 alpha is differently regulated
      in leaves and roots under cold stress.

PMID- 8534857
TI  - Tabulation of thirty-one putative new genes from cyanobacteria.
AB  - In the context of other research cyanobacterial DNA sequences were obtained from
      genomic clones selected from libraries at random. Sequences from Synechococcus
      PCC 6301, Calothrix PCC 7601 and Calothrix D253 are now available from the
      GenBank/EMBL/DDBJ databases (accession number Z47089 to Z47128, Z47129 to Z47149
      and Z47150 to Z47197, respectively) and have been searched for similarity to
      known sequences. Thirty-one putative new genes (encoding putative products with
      at least 40% identity over at least 50 amino acids, or the converse) are listed
      along with one sequence from Synechococcus PCC 6301 that had been isolated
      previously.

PMID- 8534858
TI  - The sequence surrounding the translation initiation codon of the pea plastocyanin
      gene increases translational efficiency of a reporter gene.
AB  - The 5'-upstream region of the pea plastocyanin gene (petE) directed 5-10-fold
      higher levels of beta-glucuronidase (GUS) activity than the cauliflower mosaic
      virus 35S promoter in transgenic tobacco plants, although the levels of GUS mRNA
      were similar. The sequence (AAAAAUGG) around the translation initiation codon of
      petE enhanced translation of the GUS mRNA 10-fold compared to translation from
      the GUS translation initiation codon in transgenic tobacco plants and transfected
      protoplasts.

PMID- 8534859
TI  - Biological and clinical role of angiogenesis in breast cancer.
AB  - Angiogenesis, the process leading to the formation of new blood vessels, plays a
      central role in tumor progression of solid neoplasia. The switch from the
      avascular to the vascular phase is generally accompanied by rapid primary tumor
      growth and local invasiveness. Furthermore, angiogenesis is also necessary both
      at the beginning and at the end of the development of distant metastasis and is
      implicated in the phenomenon of dormant micrometastases. The angiogenic activity
      of both the primary tumor and its metastases is the result of the net balance
      between angiogenic peptides and natural inhibitors, and it is regulated by
      multiple biochemical and genetic mechanisms. In normal tissues of the adult,
      unlike invasive cancers, the angiogenic inhibitory pathway predominates. Several
      experimental and clinico-pathologic studies have confirmed that angiogenesis is
      specifically involved in transformation and progression of human breast cancer.
      In particular, clinicopathologic studies have found that the degree of
      vascularization of primary invasive human breast cancer is heterogeneous and
      correlates with the prognosis of patients. A number of antiangiogenic agents have
      been recently discovered, and some are under early clinical evaluation. Thus,
      angiogenic activity of the tumors represents a potentially novel anticancer
      therapeutic target. This issue of Breast Cancer Research and Treatment reports on
      the most relevant basic biological aspects of angiogenesis, on its clinical role
      in breast cancer prognosis, and on the implications of inhibition of angiogenesis
      for future novel anticancer therapeutic approaches.

PMID- 8534860
TI  - The influence of angiogenesis research on management of patients with breast
      cancer.
AB  - The diagnosis and treatment of patients with breast cancer is beginning to be
      influenced by new ideas and discoveries emerging from the field of angiogenesis
      research. This field, pursued in the laboratory for more than 20 years, has in
      the past 5 years generated clinical applications. Some of these applications have
      begun to change current thinking about cancer patients and especially about those
      with breast cancer. I here discuss how an understanding of the process of
      angiogenesis may contribute to improved management of patients with breast
      cancer.

PMID- 8534861
TI  - The modulation of thrombospondin and other naturally occurring inhibitors of
      angiogenesis during tumor progression.
AB  - Fifteen different natural inhibitors of angiogenesis have now been identified
      that are produced by mammalian cells and are able to block in vivo
      neovascularization. The majority of these are able to inhibit endothelial cell
      activities in vitro and all those tested have demonstrated significant antitumor
      activity. Most normal cells produce inhibitors of neovascularization that must be
      downregulated before the cells can develop into angiogenic, malignant tumors. In
      several cases the production of inhibitors ceases when tumor suppressor genes are
      inactivated. In the BT549 human breast carcinoma cell line, the reintroduction of
      a wild type p53 tumor suppressor gene resulted in the stimulation of the
      secretion of an inhibitor of angiogenesis, thrombospondin-1, and as a result the
      cells lost their angiogenic phenotype and became able to suppress angiogenesis
      induced by the parental tumor line. These results provide a new example of tumor
      suppressor gene control of a natural inhibitor of angiogenesis and add support to
      the concept that thrombospondin loss may play an important role in the
      development of some human breast cancers.

PMID- 8534862
TI  - The role of vascular endothelial growth factor in pathological angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) is a diffusible endothelial cell
      specific mitogen and angiogenic factor that can also increase vascular
      permeability. By alternative splicing of mRNA, VEGF may exist as one of four
      different isoforms that have similar biological activities but differ markedly in
      targeting and bioavailability. The VEGF receptors are specifically expressed in
      the cell surface of vascular endothelial cells. Recent studies point to VEGF as a
      major regulator of physiological angiogenesis, such as developmental and
      reproductive angiogenesis. Furthermore, VEGF appears to be a crucial mediator of
      blood vessel growth associated with tumors and proliferative retinopathies. The
      VEGF mRNA is up-regulated in the majority of human tumors and the VEGF protein is
      increased in the aqueous and vitreous humors of patients with proliferative
      retinopathies. Anti-VEGF antibodies have the ability to suppress the growth of a
      variety of tumor cell lines in nude mice and also can inhibit angiogenesis in
      animal models of intraocular neovascularization. Therefore, strategies aimed at
      antagonizing VEGF may form the basis for an effective treatment of tumors and
      retinopathies. Furthermore, VEGF-induced angiogenesis is sufficient to achieve a
      therapeutic endpoint in models of coronary or limb ischemia.

PMID- 8534863
TI  - Regulation of the expression of the VEGF/VPS and its receptors: role in tumor
      angiogenesis.
AB  - Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPS)
      plays a crucial role for the vascularization of tumors including breast cancers.
      Tumors produce ample amounts of VEGF, which stimulates the proliferation and
      migration of endothelial cells (ECs), thereby inducing tumor vascularization by a
      paracrine mechanism. VEGF receptors (VEGF-Rs) are highly expressed by the ECs in
      tumor blood vessels. VEGF expression can be induced in various cell types by a
      number of stimuli including hypoxia, differentiation, growth factors and tumor
      promoters of the phorbol ester class, such as TPA. The VEGF inductive pathways
      comprise kinases, oncogenes, tumor suppressor genes, and steroid hormone
      transcription factors, many of which seem to converge on the activator protein
      (AP-1) transcription factor. Much less is known about the regulation of VEGF-R
      expression, which is restricted to ECs. This expression is greatly enhanced in
      diseased tissue such as solid tumors. So far, it appears that growth factors,
      cytokines, and tumor promoters are involved in the control of VEGF-R expression.
      Here we review current knowledge about the regulation of the expression of VEGF
      and its receptors.

PMID- 8534864
TI  - Molecular and pharmacologic targeting of angiogenesis factors--the example of
      pleiotrophin.
AB  - Polypeptide growth factors contribute to the development and maintenance of
      normal tissues and are essential for the growth and metastasis of solid tumors.
      During tumor progression these factors function as autocrine stimulators of tumor
      cells and/or serve to recruit stromal tissue and blood supply to the expanding
      tumor. In particular, tumor-induced angiogenesis appears to be significant not
      only for local tumor growth but also for metastasis to distant organ sites. We
      purified several years ago the heparin-binding growth factor pleiotrophin (PTN)
      from the supernatants of human breast cancer cells and demonstrated that PTN can
      serve as an angiogenesis factor. We found the gene expressed in a number of human
      tumor cell lines as well as in human tumor tissues. Here we present different
      approaches to inhibit production and function of this growth factor. Finally we
      discuss how the experience from this growth factor can be applied to improve our
      understanding of the role of other factors thought to contribute to tumor
      angiogenesis.

PMID- 8534865
TI  - Current pathologic methods for measuring intratumoral microvessel density within
      breast carcinoma and other solid tumors.
AB  - Abundant evidence has shown that tumor growth and metastasis are dependent upon
      tumor angiogenesis (TA). TA refers to the growth of new vessels toward and within
      the tumor. Until TA occurs, tumors grow no larger than 2-4 mm in diameter. Also,
      TA is necessary at the beginning and at the end of the metastatic cascade of
      events. Thus, it seems reasonable that increasing intratumoral microvascular
      density (iMVD) might correlate with greater tumor aggressiveness, such as a
      higher frequency of metastases and/or decreased survival. Indeed, in 1991 my
      colleagues and I reported a statistically significant association between greater
      incidence of metastases in patients with breast carcinoma and increasing iMVD.
      Microvessel density was measured with a light microscope in a single area of
      invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel
      density (neovascular "hot spot"). This was done after endothelial cells, lining
      the microvessels, had been highlighted with anti-factor VIII-related antigen/von
      Willebrand's factor (F8RA/vWF). Subsequent studies by other investigators, using
      either anti-F8RA/vWF or other relatively vessel-specific reagents such as anti
      CD31, have shown that the association of greater tumor aggressiveness with
      increasing iMVD exists not only in breast carcinoma, but also in other solid
      tumors. This article reviews the methods of highlighting intratumoral vessels and
      describes the techniques for counting these vessels for assessing iMVD.

PMID- 8534866
TI  - Novel methods for the determination of the angiogenic activity of human tumors.
AB  - At present the most used method to quantify tumor angiogenesis in human solid
      tumors is the count of intratumoral microvessels in the primary lesion. This
      method requires the use of specific markers to vascular endothelium and of
      immunohistochemical procedures to visualize microvessels. Several studies have
      found that intratumoral microvessel density (IMD) determined in the primary tumor
      is significantly associated with metastasis and prognosis in some solid
      neoplasia, particularly in operable breast carcinoma. The subjective evaluation
      of IMD made by two observers at the microscope is rapid and of low cost, but
      presents some difficulties, mainly the identification of the most vascularized
      area ("hot-spot") within each tumor. This method can be improved upon to attain a
      better reproducibility among different pathologists. For example, the use of a
      multiparametric computerized image analysis system (CIAS) seems to be a promising
      tool to improve accuracy, feasibility and reproducibility of microvessel counts,
      although there are still some open technical problems to completely automate its
      use. Angiogenic activity is the result of a balance between angiogenic stimuli
      and angio-inhibition. Therefore the determination of angiogenic peptides and/or
      natural angiogenesis inhibitors in the tumor tissue, serum, or urine of cancer
      patients seems to be a promising alternative to microvessel counting. At present
      it is possible to determine the expression of basic fibroblast growth factor
      (bFGF), vascular endothelial growth factor, and transforming growth factor beta
      using immunohistochemical methods. Serum and urine levels of bFGF can be assessed
      using an immunoenzymatic assay. Methods used to assess the expression and levels
      of urokinase-type plasminogen activator (uPA) or plasminogen activator inhibitor
      1 (PAI-1) have also been developed, and correlate with angiogenic activity and
      prognosis of patients with breast cancer. Finally, some investigational methods
      to assess angiogenesis in vivo are presented and discussed. Angiogenesis is a
      very complex phenomenon. Thus it seems reasonable to hypothesize that its
      assessment by using concurrently several of the available methods may provide
      more valid, accurate, and comprehensive information on the angiogenic activity of
      each single tumor. For a reliable and reproducible assessment of angiogenesis for
      all of the assays, validation procedures and quality control protocols are
      mandatory.

PMID- 8534867
TI  - Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and
      the association with vascular endothelial growth factor expression.
AB  - The importance of tumor angiogenesis in the process of tumor growth and
      progression in solid tumors has been widely accepted. We have investigated the
      significance of tumor angiogenesis as a prognostic indicator in a retrospective
      study including 328 primary breast cancer patients. The postoperative survey
      demonstrated that the microvessel density (MVD) evaluated by immunocytochemical
      staining for factor VIII-related antigen is a potent prognostic indicator. The
      relapse-free survival (RFS) rate of patients with over 100 microvessels/mm2 in a
      microscopic field was significantly worse compared to that of patients with less
      than 100 microvessels/mm2 (p < 0.00001). The significance of MVD was found in
      both node-negative and node-positive patients (p < 0.005 and p < 0.01,
      respectively). Multivariate analysis confirmed that MVD is an independent
      prognostic indicator for RFS. In the background factor analysis, MVD was
      significantly correlated with the number of metastatic nodes (p < 0.01). In
      addition, the immunocytochemical analysis for vascular endothelial growth factor
      (VEGF) demonstrated a close association between the increase in MVD and the
      expression of VEGF (p < 0.001). VEGF status also was a significant prognostic
      indicator in univariate analysis for RFS (p < 0.01). It was concluded that MVD is
      a potent prognostic indicator in primary breast cancer. Furthermore, it was also
      suggested that VEGF plays crucial roles in the promotion of angiogenesis in
      breast cancer.

PMID- 8534868
TI  - Prognostic value of intratumoral microvessel density, a measure of tumor
      angiogenesis, in node-negative breast carcinoma--results of a multiparametric
      study.
AB  - In the present study we update previous results on the prognostic value of
      intratumoral microvessel density (IMD), determined immunocytochemically using the
      monoclonal antibody CD-31 and a standard streptavidin-immunoperoxidase technique,
      published in the J Clin Oncol 12:454-466, 1994. This study was undertaken in
      those 211 node-negative breast cancer (NNBC) cases of that series of which we had
      pathological material available to determine all the prognostic indicators. The
      median period of follow-up has been extended to 78 and 80 months for relapse-free
      survival (RFS) and overall survival (OS), respectively, and new biological
      indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expression) were
      included in the analysis. The main results obtained are: i) a confirmation that
      IMD is not associated with the other biological markers studied, i.e. expression
      of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD
      was weakly associated only with histological grade (p = 0.053); ii) IMD remains a
      highly significant prognostic factor for RFS and OS (p < 0.0001 and p = 0.018,
      respectively) in univariate analysis; iii) in multivariate analysis on RFS, IMD
      (likelihood ratio test (LRT) = 30.16; p < 0.0001), 67 kDa laminin receptor (LRT =
      9.80; p = 0.0017), the IMD/67 kDa laminin receptor interaction (LRT = 8.62; p =
      0.0033), tumor size (LRT = 8.56; p = 0.0034), and p53 protein (LRT = 4.96; p =
      0.025) are significant and independent prognostic indicators. For OS, only tumor
      size (LRT = 8.34; p = 0.0038), menopausal status (LRT = 5.16; p = 0.023), p53
      protein (LRT = 4.37; p = 0.036), and IMD (LRT = 4.05; p = 0.044) retain a
      significant and independent prognostic value. The results of this study confirm
      the prognostic importance on RFS of the variables previously tested, but not of
      peritumoral lymphatic vessel invasion. A novel finding is that 67 kDa laminin
      receptor and the IMD/67 kDa laminin receptor interaction are also significant and
      independent variables. For OS, the results confirm that both IMD and tumor size
      are significant and independent variables. With prolonged follow-up the novel
      finding that emerges is the prognostic importance of menopausal status and p53
      protein. This new information could be useful for a more accurate selection of
      high-risk NNBC patients who require careful follow-up and may benefit from
      adjuvant therapy.

PMID- 8534869
TI  - The prognostic value of quantitative angiogenesis in breast cancer and role of
      adhesion molecule expression in tumor endothelium.
AB  - Angiogenesis is the formation of new capillaries from the existing vascular
      network and is essential for tumor growth and metastases. Increased microvessel
      density in breast cancer is associated with lymph node metastasis and reduced
      survival. We have assessed tumor vascularity in 211 breast carcinomas using a
      more rapid technique based on a Chalkley point eyepiece graticule. We confirmed
      using this method a significant reduction in overall survival between patients
      stratified by Chalkley count in both a univariate (p = 0.02) and multivariate (p
      = 0.05) analysis. Since studies have suggested that cell adhesion molecules
      (CAMs) might be important in the angiogenic process, and interaction of
      neoplastic cells with this neovasculature is a significant step in tumor
      metastasis, we have also examined the expression of CAMs in a subset of these
      tumors (n = 64). Using immunohistochemistry we observed widespread and intense
      staining on the endothelium of tumor-associated vessels for PECAM (100%), ICAM 1
      (69%), and E- and P-selectins (52% and 59% of cases respectively). Endothelial
      expression of the selectins was more prominent at the tumor periphery.
      Immunoreactivity of ICAM-1 (34%), PECAM (1.6%), and E- and P-selectins (7% and
      37% of cases respectively) was also observed on the neoplastic element of the
      tumors.

PMID- 8534871
TI  - Antibody-directed targeting of the vasculature of solid tumors.
AB  - An attractive strategy for the therapy of carcinomas and other solid tumors would
      be to target cytotoxic agents or host immune effectors to the endothelial cells
      of the tumor vasculature rather than to the tumor cells themselves. The key
      advantage of this approach is that the endothelial cells are freely accessible
      through the blood whereas the tumor cells are, for the most part, inaccessible.
      Also, endothelial cells are similar in different tumors, making it feasible to
      develop a single reagent for treating numerous types of cancer. In this chapter,
      we review progress in this "vascular targeting" approach, from the validation of
      the concept in a mouse model to the characterization of the TEC-11 antibody
      against endoglin, an endothelial cell proliferation marker that is upregulated on
      endothelial cells in miscellaneous human solid tumors. In addition, we review
      other tumor endothelial cell markers that are candidates for vascular targeting
      in man.

PMID- 8534870
TI  - Potentiation of cytotoxic therapies by TNP-470 and minocycline in mice bearing
      EMT-6 mammary carcinoma.
AB  - The ability of the antiangiogenic agents TNP-470 and minocycline, singly or in
      combination, to potentiate the antitumor effects of several cytotoxic therapies
      was assessed in the murine EMT-6 mammary carcinoma as well as in two drug
      resistant sublines of that tumor designated EMT-6/CTX and EMT-6/CDDP. The
      antiangiogenic agents alone or in combination did not alter the growth of the
      tumors. However, their administration along with cyclophosphamide, CDDP, or
      thiotepa substantially increased the tumor growth delay produced by these
      cytotoxic therapies in tumors responsive to the drugs--the increase was about 2
      fold for TNP-470 and minocycline together. In drug resistant tumors, treatment
      with the antiangiogenic agents did not reverse drug resistance but did increase
      the effect of the cytotoxic drugs. Treatment with TNP-470/minocycline also
      increased the oxygenation of each of the three tumors. Thus, TNP-470/minocycline
      administration increased the efficacy of fractionated radiation therapy,
      especially when used along with a perflubron emulsion oxygen delivery
      agent/carbogen. These results indicate that treatment regimens including
      therapies directed toward the proliferating normal cells within a tumor mass as
      well as therapies directed toward the malignant cells can produce improved
      outcomes.

PMID- 8534872
TI  - The clinical experience with antiangiogenic agents.
AB  - Antiangiogenic agents have been recently recognized to be potentially useful in
      the treatment of malignant processes. There has been a resulting flood of these
      agents into the clinical research field, forcing researchers to consider the
      unique problems which these agents pose. As these are agents with a novel,
      angiostatic mechanism of action, new clinical trial designs may become necessary
      to move these agents from the phase 1 level on to clinical use. Currently,
      several of these agents are being or have been tested in clinical trials. In this
      article, we review the available clinical data with antiangiogenic agents from
      other investigators, and our own experience with pentosan polysulfate.

PMID- 8534873
TI  - [Quality of life, subjective health status and health and life satisfaction in
      rheumatoid arthritis].
AB  - A Japanese version of Arthritis Impact Measurement Scales (AIMS) was developed
      after the original AIMS Version 2 and utilized for Quality of Life (QOL)
      measurement in 691 patients with Rheumatoid Arthritis (RA). Various medical
      (physical and laboratory) examinations, which are widely used in the clinical
      settings for the assessment of RA activity and severity, were also performed by
      physicians. Interrelationships between QOL, patient subjective health status, and
      health and life satisfaction were analyzed with the following results: 1: The
      effect of QOL impairment by RA upon patients' subjective health rating and health
      satisfaction were not constant over the range of severity of disease status. Pain
      was found to lower overall subjective health and health satisfaction regardless
      of RA class. On the other hand, while the deterioration of mobility aspects of
      QOL had negative effects upon patients' subjective health status and satisfaction
      among less-disabled RA patients, any of physical aspects of QOL, including the
      degree of mobility impairment, showed no significant association with patients'
      subjective health status and satisfaction in the more disabled. 2: Psychological
      aspects of QOL (mood and tension) had significant associations with patients'
      subjective health status and satisfaction. In the less severe group, mood
      impairment had a significant effect on subjective health and satisfaction, while
      in the more severe group tension showed a significant association. It was
      indicated that management of psychological aspects of QOL is important in RA
      patients to improve and advance their subjective health status and satisfaction.
      3: Although social aspects of QOL, i.e. social support, social life and job
      status, showed no significant relationship to subjective health rating and health
      satisfaction, those with less disease severity who lacked social support and who
      had a jobless state were likely to have lower disease acceptance and life
      satisfaction, while those with more severe disease who had less social
      interaction manifested lower life satisfaction. These results suggested that
      social aspects of QOL, while not directly associated with subjective health
      rating, could be important factors affecting disease acceptance and life
      satisfaction.

PMID- 8534874
TI  - [Cause of death for handicapped taken care of at home due to chronic neurological
      disorders].
AB  - Prognosis of patients with neurological diseases cared for at home and visited by
      physicians from our clinic since 1985 was studied. Since prognosis may differ by
      conditions of patient care at home, duration since disease onset etc., the
      problems related to patient care at home need to be made clear. The "at home"
      patient group (Group H) consisted of 21 patients who were visited by physicians
      for more than 3 months. The other group (Group A) consisted of 22 patients with
      neurological diseases and who visited periodically the outpatient clinic of our
      hospital. The two groups were compared as to prognosis. Mean duration of the
      underlying disease of Group H and A were 1765.5 and 1238.1 days, respectively.
      The most frequent direct cause of death in Group H was congestive heart failure
      and that in Group A was cerebrovascular lesion. Cases with congestive heart
      failure as direct cause of death had a longer mean duration of the direct cause
      of death than those with causes of death other than congestive heart failure in
      Group H. Length of bed-ridden condition had no significant correlation to the
      duration of the direct cause of death in Group H. The following conclusions were
      1. For the handicapped taken care of at home, duration of the direct cause of
      death was significantly longer than for patients treated at the hospital. 2.
      Congestive heart failure was the most prevalent death cause in Group H.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8534875
TI  - [Relationship between health services and medical care expense].
AB  - The relationship of health services for the elderly to medical care expenses for
      persons over 40 in age was studied by examining data for fiscal year 1992 in 393
      municipalities among the municipalities throughout the country where actual
      conditions have been surveyed. Analysis was by multiple regression analysis.
      Results showed that medical expenses for every disease were lower in the
      municipalities which had a higher rate of execution of general health
      examinations, stomach cancer examinations, and home-visit guidance. This tendency
      was particularly remarkable in the case of diseases of the circulatory system. In
      contrast, medical care expenses were high in the municipalities which had a
      higher demand rate for medical counseling or a higher rate of attendance in
      health consultation. However the relation of rate of execution of functional
      training, or attendance rate at the health education sessions, or the rate of
      performance of detailed examinations was not clear.

PMID- 8534876
TI  - [Comparison of activities of daily living (ADL), medical treatment and blood
      pressure of elderly participants and non-participants in health examinations].
AB  - A study was conducted to determine the characteristics of the elderly who do not
      participate in health examinations, and to obtain basic health data on the
      elderly for developing a community health care plan. Elderly persons aged 60 or
      over who had not participated in mass health examinations in 1991 were
      interviewed regarding their conditions of activities of daily living (ADLs), and
      medical treatment, and their blood pressure was measured. Participation rate for
      health examinations in the elderly was 66%. Of the total 245 elderly who did not
      participate in health examinations, data from 215 (88%; 92 men and 123 women)
      were obtained. 1) The average age of the elderly who did not participate in
      health examinations was 3 years higher in men and 5 years higher in women than
      that of those who did participate (p < 0.01), and there were a larger number of
      persons aged 80 years or over. 2) The percentage of persons with a history of
      adult diseases such as cardiovascular disease was 63% which was 10% higher than
      those who participated in examinations (p < 0.01). 3) The percentage of persons
      requiring help in walking and/or mobility (13%) and bathing (10%) was higher than
      those who participated in examinations (p < 0.01). For seeing and hearing there
      were no differences between groups in the percentage of disabled persons. 4)
      There were more hypertensive people (> 160/95 mmHg) in those who did not
      participate in examinations (p < 0.01), but the percentage of the people who
      needed treatment (> 180/100 mmHg) was not different.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8534877
TI  - [Effect of repeated toothbrushing instructions on periodontal health in a
      community].
AB  - This study was conducted to compare the effect of frequency of toothbrushing
      instruction using the Toothpick Method in a community periodontal health program.
      Two courses, one consisting of three monthly toothbrushing instructions and the
      other a single instruction session, were given to residents in a small town.
      Thirty-one subjects (mean age; 48.7 +/- 9.2) in the three-time instruction course
      and 40 subjects (mean age; 55.2 +/- 8.3) in the single instruction course
      participated in dental examinations. During the first visit, the subjects of the
      both groups attended a class for dental health education, and observed their
      dental plaque using a phase contrast microscope, and the condition of their teeth
      and periodontal tissue was recorded. They were instructed to brush their teeth by
      the Toothpick Method. After 1 year, the subjects of the both groups were examined
      and required to fill out a questionnaire. The percentage of sites with gingival
      redness and swelling significantly decreased after 1 month, 2 months and 1 year
      in the three-time instruction group. In the single instruction group, however,
      gingival redness and swelling did not change after 1 year. The percentage of
      sites with bleeding on probing significantly decreased in the both groups. The
      improvement ratio for the CPITN code was higher in the three-time instruction
      group than the other. The questionnaire showed that subjects in the three-time
      instruction group brushed their teeth more actively, and were more satisfied with
      the program than those in the single instruction group. These results show that
      the three-time instruction course was more effective than the single instruction
      course.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534878
TI  - [Cost benefit analysis of care of low-birth-weight infants].
AB  - A model for cost-benefit analysis of medical care of low-birth-weight infants was
      proposed in order to evaluate its economic efficiency using the notion of an
      expected value, routinely used in economics. The expected cost and benefit when a
      low-birth-weight infant is born were calculated and compared. Cost includes the
      hospital charges and the charges for long-term care of a handicapped survivor.
      Benefit includes the present value of lifetime earnings. Benefit/Cost Ratio was
      selected as a criterion to determine efficiency, with values exceeding 1
      representing the case where the expected benefit exceeds the expected cost,
      meaning a net economic gain. Actual values were substituted in the model for cost
      benefit analysis of care of very-low-birth-weight infants. Benefit/Cost Ratios
      corresponding to various birth weights were calculated, and the break-even point
      was found to be about 800 g, which was consistent with several former reports.
      However sensitivity analysis indicated that Benefit/Cost Ratio was affected
      greatly when either the discount rate or charges for long-term care of a
      handicapped survivor was changed. A net economic loss would be attributable to
      the higher incidence of sequela corresponding to very-low-birth-weight, which
      would suggest that to enhance economic gain investment in care for increasing the
      rate of intact survivals is essential. Further study is required to define
      adequate values, and to determine the grade of handicap as well as lifetime
      earnings.

PMID- 8534879
TI  - [Prevalence and correlates of major depressive episode among the elderly in a
      community in Japan].
AB  - A random sample of 205 persons from a community of about 45,500 residents, aged
      65 years or older, in a city in Japan, was surveyed using an interview schedule
      including a structured psychiatric interview to analyze prevalence of major
      depressive episode (DSM-III-R). A total of 157 (77%) participated in the study.
      Results were as follows: 1) The Prevalence of major depressive episode during the
      past 6 months was 2.1% for males and 3.7% for females among the 155 respondents
      who completed the psychiatric interview. 2) Significantly higher prevalence
      during the past 6 months was observed in those who were physically inactive in
      the past year than in those physically active (p < 0.05). 3) Levels of
      satisfaction with available social support were significantly lower in those who
      experienced major depressive episode during the past six months than in those who
      experienced no depressive episode (p < 0.05). 4) Levels of life satisfaction (PGC
      scale score) and cognitive functioning were significantly lower in those
      experienced major depressive episode during the past six months than in those who
      experienced no depressive episode (p < 0.05).

PMID- 8534880
TI  - [Medical care of AIDS patients by hospitals in Tokyo].
AB  - An anonymous questionnaire survey was performed in 1991 in all 749 hospitals in
      Tokyo, by the Tokyo Metropolitan Government's Acquired Immunodeficiency Syndrome
      (AIDS) and Human Immunodeficiency Virus (HIV) Infection Research Team, to collect
      information relating to hospital services for persons with AIDS or HIV infection.
      The response rate was 61%. The following results were obtained: 1) Sixty-five
      hospitals (14%) had seen persons with AIDS or HIV infection. Hospitals with a
      greater number of beds had more experience in seeing persons with AIDS or HIV
      infection. Thirty-four hospitals (7%) provided outpatient services for patients
      with AIDS or HIV infection, and 30 hospitals (7%) had the facilities for
      inpatients. Three hundred forty-seven hospitals (78%) were capable of HIV
      antibody tests. Ninety-one hospitals (20%) had organized training courses for
      hospital workers to prevent HIV infection. Two hundred eight hospitals (46%)
      expressed preference that persons with AIDS or HIV infection be treated at public
      (non-private) hospitals. 2) The results of multivariate logistic regression
      analysis indicated that a hospital's acceptance of persons with AIDS or HIV
      infection for diagnosis or treatment was significantly related to past experience
      in seeing persons with AIDS or HIV infection, availability of an examination room
      that protects privacy of patients, presence of a department of internal medicine,
      and awareness of the availability of special AIDS counselor dispatch services by
      the Tokyo metropolitan government.

PMID- 8534881
TI  - [Trends and analysis of HIV and sexually transmitted disease infection in foreign
      commercial sex workers in Japan].

PMID- 8534882
TI  - [Long-term changes in body mass index in rural inhabitants: Takasu study].
AB  - Based on community health examination data (1975-1992) of Takasu, a rural town in
      Hokkaido Prefecture, long-term changes in body mass index (BMI) were studied and
      contour maps were developed. The results were as follows: 1) A high median BMI,
      23 or more, appeared in female age groups from 50's to 70's during the
      observation period, whereas the high median BMI appeared in male age groups 30's
      and 40's after 1981. 2) Median BMI in age groups 30's and 40's at the time of the
      initial observation increased gradually with age in both sexes.

PMID- 8534883
TI  - Liquid secondary-ion mass spectrometry of peptides containing multiple tyrosine-O
      sulfates.
AB  - The behavior of peptides containing multiple tyrosine-O-sulfates in liquid
      secondary-ion mass spectrometry (LSIMS) has been investigated. In the positive
      ion spectra of the peptides containing two tyrosine-O-sulfates, Cionin and CCK
      associated C-terminal nonapeptide (CAP-9), the completely desulfated [M+H-2SO3]+
      ions formed the base peaks, accompanying the significantly less-intense [M+H]+
      and [M+H-SO3]+ ions. In the negative-ion spectra of these peptides, the [M-H]-
      and [M-H-SO3]- ions gave prominent peaks with significantly weaker [M-H-2SO3]-
      ions. In the case of a peptide containing three tyrosine-O-sulfates,
      [Tyr(SO3H).1]CAP-9, the completely desulfated [M+H-3SO3]+ ion again formed the
      base peak in the positive-ion spectrum. On the other hand, the sulfated tyrosine
      containing [M+H]+, [M+H-SO3]+, and [M+H-2SO3]+ ions were of negligible abundance
      compared to the spectra of peptides containing two tyrosine-O-sulfates. We
      observed an intriguing 'ladder fragmentation pattern' in the negative-ion
      spectrum of this triply-sulfated peptide. The ladder consisted of the [M-H]-, [M
      H-SO3]-, and [M-H-2SO3]- ions, but without the completely desulfated [M-H-3SO3]-
      ion. These characteristic fragmentation patterns of sulfated tyrosine-containing
      peptides were considered to bear a close correlation with the inherent acid
      lability of a tyrosine-O-sulfate in solution. A possible mechanism has been
      proposed to explain the fragmentation patterns in the gaseous phase, in which a
      proton plays a decisive role.

PMID- 8534884
TI  - Collisionally-activated dissociation spectra of linear peptides in matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Collisionally-activated dissociation (CAD) studies of linear peptides were
      performed using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry. Four different gases, viz. helium, nitrogen, argon and xenon, were
      introduced into a gas cell, installed close to the ion source of TOF mass
      spectrometer, to obtain high-energy CAD information. The CAD spectral patterns
      for the linear peptides obtained using the four gases were almost the same as
      each other. The fragments characteristically obtained in conventional high-energy
      CAD using tandem mass spectrometry were observed also in these spectra. A
      difference between CAD spectra and post-source decay product-ion spectra has been
      demonstrated.

PMID- 8534885
TI  - Electron impact mass spectra of some 1-(2-furyl)- and 1-(2-thienyl)-2-(2
      benzothiazolyl)ethenes.
AB  - The electron impact mass spectra of some 1-(2-furyl)- and 1-(2-thienyl)-2-(2
      benzothiazolyl) ethenes have been recorded and the identity of various ions in
      the mass spectra established. The compounds examined (1-10) exhibit two main
      fragmentation routes. On one hand, fragmentation of the furan and thiophene
      nuclei and the formation of cyclopropenylethyne cations with very significant
      abundance and on the other hand, fragmentation of the benzothiazole nuclei on
      characteristic pathways. Compounds 6-10 also show two additional fragmentation
      routes.

PMID- 8534886
TI  - Sequencing peptides without scanning the reflectron: post-source decay with a
      curved-field reflectron time-of-flight mass spectrometer.
AB  - A time-of-flight mass spectrometer has been developed using a reflectron in which
      the voltages placed on the lens elements correspond to a function describing the
      arc of a circle. This curved-field reflectron enables acquisition of focused
      product-ion mass spectra at a single reflectron voltage. In this paper, we
      present results from this instrument for the amino acid sequencing of several
      peptides and describe the method of mass calibration.

PMID- 8534887
TI  - Ion dissociation reactions induced in a high-pressure quadrupole collision cell.
AB  - This work concerns a new high-pressure quadrupole collision cell, designed for
      triple-quadrupole mass spectrometers. This new collision cell operates at
      pressures up to 10 mTorr, an order of magnitude higher than conventional cells of
      this type. Previous investigations have concentrated upon the significant
      increases in transmission efficiency and in resolving power for fragment ions
      which result from the use of this new design. The present work reports an
      investigation into the nature of the dissociation reactions which can be induced
      by collisions in this high-pressure cell. Charge-site-remote fragmentations of a
      simple precursor ion were chosen as a test case, and were found to be observable
      at laboratory collision energies lower by a factor of 4-5 than those found
      previously to be necessary when using conventional low-pressure quadrupole
      collision cells. It was also shown that the charge-site-remote reactions were
      accompanied by the mixed-site-fragmentation reactions described by Tuinman and
      Cook (J. Am. Soc. Mass Spectrom. Vol. 1, p. 85 (1989)). Ionization of collision
      gas was observed in the case of xenon. Efforts to observe charge-site-remote
      fragmentations of peptide ions were marginally successful. Highly basic peptides,
      which have been problematic for sequencing by low-energy tandem mass
      spectrometry, did not yield useful fragment-ion spectra in the new cell. The
      fragmentation behaviour of protonated Leu-enkephalin, for which fragmentation
      pathways have been thoroughly studied previously, suggested that the observed
      spectra reflected integration of the fragmentation kinetics over a considerably
      longer time, thus involving many more reaction steps. These combined observations
      are considered in terms of a qualitative model based on a rapid decrease of ion
      kinetic energy during passage through the cell, with much longer residence times
      than for conventional quadrupole cells.

PMID- 8534888
TI  - Peptide characterization using bioreactive mass spectrometer probe tips.
AB  - A method has been developed for the rapid and sensitive mass spectrometric
      characterization of peptides. The approach uses bioreactive mass spectrometer
      probe tips, incorporating covalently bound enzymes, which are capable of
      modifying biomolecules for analytical purposes. In the demonstrated cases,
      enzymatic proteolysis is initiated upon application of analyte to the probe tips,
      time is allowed for digestion, and the products are analyzed using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry. The probe
      tips have been used for proteolytic mapping and partial sequence determination of
      picomole quantities of peptide. Analysis times were approximately 30 min. Two
      methods of database search were utilized. The first used limited peptide sequence
      information and parent molecular weight, while the second used exclusively the
      molecular weights of a number of endoproteolytic fragments. A simple method of
      comparing the match of experimental data for a tryptic digest with the results of
      a search is described.

PMID- 8534889
TI  - Investigation of crudes of synthesis of [Leu31, Pro34]-neuropeptide Y by
      capillary zone electrophoresis/mass spectrometry.
AB  - [Leu31, Pro34]-Neuropeptide Y is a thirty-six amino-acid peptide which has a
      measured relative molecular mass of 4222. Solid-phase synthesis of this peptide
      resulted in complex crudes of synthesis which were examined by capillary zone
      electrophoresis (CZE)/electrospray ionization mass spectrometry (ES-MS). The
      separation efficiency of CZE combined with the mass specificity of mass
      spectrometry yielded rapid and reliable information on the target peptide and a
      number of associated side products, which were mainly acetylated peptide
      sequences having relative molecular masses in the range 2240-4101. Such
      incomplete or, as they are commonly called, difficult sequences are provoked by
      problems of swelling and aggregation of the growing peptide chains in the course
      of synthesis. The use of mass spectrometry is indispensable for obtaining
      reliable information on the inevitable side products. Initial tuning of the ion
      source and optimization of the coupling between the CZE system and the mass
      spectrometer were achieved by performing a number of measurements pertaining to
      artificially made mixtures of commercial neuropeptides.

PMID- 8534890
TI  - An improved method for clenbuterol screening using high resolution selected ion
      recording.
AB  - A method has been developed using reliable GC derivatization techniques
      interfaced with a high resolution mass spectrometer. The method has proved
      successful for the detection of low levels (less than 1 ppm) of clenbuterol in
      complex biological matrices. Selected ion recording of two characteristic
      isotopic fragment ions provides a specific mode of detection by verifying the GC
      retention time of these ions and also by comparing their relative abundance.
      Analysis of urine samples demands higher mass spectrometric resolution, and 40
      000 (10% valley) was found to be a prerequisite for accurate integration of the
      drug-related chromatographic peaks. The method developed is suitable for
      adaptation to a completely unattended automated routine incorporating sample
      injection, storage and retrieval of source tuning parameters, and data
      processing.

PMID- 8534891
TI  - The characterization of the metabolites of ranolazine in man by liquid
      chromatography mass spectrometry.
AB  - The metabolism of ranolazine (RS-43285) or (+)N-(2,6-dimethylphenyl)-4[2-hydroxy
      3-(2-methoxyphenoxy)-propyl]-1- piperazine acetamide dihydrochloride was
      investigated in man using plasma samples obtained from four different clinical
      studies. The metabolite profiles following single and multiple doses of 342 mg
      instant release (IR) ranolazine, following multiple doses of 1000 mg sustained
      release (SR) ranolazine and following dosing with both ranolazine (IR) and a
      potentially co-administered drug, diltiazem, were compared. Metabolism of
      ranolazine in man was shown by LC/MS analysis to be extensive with up to seven
      primary routes of metabolism identified. N-dealkylation by hydrolysis at the
      piperazine ring produced three metabolites whilst O-demethylation and O
      dearylation at the methoxyphenoxy moiety produced a further two compounds.
      Additionally, hydrolysis of the amide group formed one other species. Oxygenation
      at various points in the molecule produced a further four metabolites. Direct
      conjugation of ranolazine with glucuronic acid and with an uncharacterized adduct
      were also identified as a route of elimination. Ten other biotransformation
      products were formed as a result of multiple metabolic steps. Conjugation was
      also associated with the desmethyl metabolite (glucuronide and unidentified
      conjugates) of hydroxylated ranolazine. In a previous publication (Journal of
      Chromatography, 1995, accepted for publication) semi-quantitative analyses of
      pooled plasma from the study where ranolazine was dosed at 1000 mg twice daily
      showed that of the twelve metabolites studied only four accounted for AUC's in
      excess of 10% of the ranolazine AUC.

PMID- 8534892
TI  - Determination of the pesticides diflubenzuron and clofentezine in plums,
      strawberries and blackcurrant-based fruit drinks by high performance liquid
      chromatographic/atmospheric pressure chemical ionization-mass spectrometry.
AB  - A high performance liquid chromatographic/atmospheric pressure chemical
      ionization-mass spectrometric (HPLC/APCI-MS) method has been developed for the
      determination of the pesticides diflubenzuron (1-(4-chlorophenyl)-3-(2,6
      difluorobenzoyl)urea) and clofentezine (3,6-bis(2-chlorophenyl)-1,2,4,5
      tetrazine) in plums, strawberries and blackcurrant-based fruit drinks. Samples
      were homogenized with acetone, extracted into dichloromethane + cyclohexane and
      cleaned-up by high performance gel permeation chromatography. HPLC was performed
      on an ODS column with methanol + water at 1 mL/min. Detection was by negative-ion
      selected-ion monitoring APCI-MS. Comparison of response with solvent and matrix
      matched standards showed some enhancement of response for the latter, and these
      standards were consequently used for quantification. The calibration was linear
      over the range 0.05-0.50 ng/microL in all three matrices. The mean overall
      recovery of diflubenzuron and clofentezine from spiked extracts (0.086 mg/kg) in
      all three matrices was 76% and 70% respectively with relative standard deviations
      of 15% and 12% respectively (n = 12). The limit of detection was both compound
      and commodity dependent and ranged from 0.01-0.05 ng/microL, equivalent to 0.003
      0.014 mg/kg in the crop.

PMID- 8534893
TI  - The development and validation of a high performance liquid chromatography
      (HPLC)/tandem mass spectrometry assay for fenticonazole in human plasma and
      comparison with an HPLC-UV method.
AB  - A method is described for the determination of fenticonazole in human female
      plasma. The method utilizes high performance liquid chromatography coupled to
      atmospheric pressure positive-ion chemical ionization triple quadrupole mass
      spectrometry. Multiple reaction monitoring is employed for selectivity and
      sensitivity which enables quantification over the range 0.5-20 ng mL-1 with
      acceptable precision and accuracy. A comparison is made with an existing HPLC-UV
      assay and the utility of the technology of combined liquid chromatography and
      tandem mass spectometry for subnanogram per mL assays is discussed.

PMID- 8534894
TI  - Identification of urinary and biliary conjugated metabolites of the neuromuscular
      blocker 51W89 by liquid chromatography/mass spectrometry.
AB  - Cisatracurium, (1R, 1'R, 2R, 2'R)-2,2-[1,5-pentanediylbis-[oxy(3-oxo- 3,1
      propanediyl]]bis[1-[(3,4-dimethoxyphenyl)-methyl]-1,2,3,4- tetrahydro-6,7
      dimethoxy-2-methylisoquinolinium] dibenzenesulphonate (51W89), is an intermediate
      acting neuromuscular blocking agent. 51W89 is one of ten isomers contained in
      Tracrium (atracurium besylate) and represents approximately 15 percent of the
      atracurium mixture. Clinical studies have indicated that 51W89 is more potent and
      is significantly weaker as a histamine releaser than atracurium. In vitro studies
      in human plasma have shown that, like atracurium, 51W89 spontaneously degrades at
      physiological pH by Hoffmann elimination to form laudanosine and the quaternary
      monoacrylate. Subsequent ester hydrolysis of the monoacrylate generates the
      monoquaternary alcohol. In rat plasma, 51W89 is also metabolized by non-specific
      carboxylesterases to the monoquaternary alcohol and the monoquaternary acid, the
      former being rapidly hydrolysed further to the more stable acid. It has been
      reported that laudanosine can be further metabolized via N-dimethylation to yield
      tetrahydropapaverine. The rate-limiting step in the degradation of 51W89 in human
      plasma is Hofmann elimination, whilst in rat plasma, the action of non-specific
      carboxylesterases is rate limiting. As part of the development of 51W89, the
      disposition of 14C-51W89 following a single intravenous bolus dose was studied in
      various animal species and humans. In the present work, we describe the
      identification of 51W89 metabolites in urine and bile from these studies by high
      performance liquid chromatography/mass spectrometry using pneumatically-assisted
      electrospray ionization coupled to an on-line radioactivity monitor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8534895
TI  - Microscopy of the gap junction: a historical perspective.
AB  - Gap junctions were discovered more than three decades ago, and since this time,
      enormous strides have been made in understanding their structure and function.
      This article summarises the part played by microscopy, within the context of
      multidisciplinary research, in the historical development of our knowledge of the
      gap junction.

PMID- 8534896
TI  - Ocular lens gap junctions: protein expression, assembly, and structure-function
      analysis.
AB  - Recent advances in understanding lens fiber gap junction formation are reviewed.
      These include studies of junctional protein expression in the embryonic lens, and
      of age related changes affecting gap junction structure and composition in the
      adult lens. An in vitro assembly system based on detergent solubilized pore
      complexes and endogenous lipids has been developed to provide information on the
      molecular interactions involved in gap junction formation and to provide material
      for structure analysis. Important information on the electrical properties of
      lens gap junction channels is obtained using electrophysiological techniques
      including planar lipid bilayer analysis and patch clamping.

PMID- 8534898
TI  - Role of gap junctions in the development of the preimplantation mouse embryo.
AB  - We have taken several approaches to study the role of gap junctional
      communication during preimplantation mouse development. Firstly, the normal
      expression pattern of gap junctions has been characterized using immunostaining
      in conjunction with laser scanning confocal microscopy. Changes in junctional
      distribution have been correlated with developmental events. We have gone on to
      study development and junctional organization in mice which naturally exhibit
      reduced cell to cell communication (DDK syndrome), and in normal mice in which
      gap junction permeability has been artificially manipulated. Furthermore, anti
      peptide antibodies have been tested for their ability to block gap junction
      communication and for the effects of such a block on subsequent development.
      Collectively, the results demonstrate that gap junctional communication plays an
      important role in the maintenance of compaction and the differentiation of an
      organized epithelium within an embryo, features which are vital for
      preimplantation development to progress successfully.

PMID- 8534897
TI  - Structural and molecular determinants of intercellular coupling in cardiac
      myocytes.
AB  - Electrical activation of the heart requires intercellular transfer of current
      through gap junctions connecting individual cardiac myocytes. Using a combination
      of light and electron microscopic techniques and molecular approaches, we have
      characterized the number, size, and spatial distribution of intercellular
      connections at gap junctions in cardiac myocytes and have also cloned, sequenced,
      and elucidated the subcellular distribution of three physiologically distinct gap
      junction channel proteins. In this review, we present evidence to suggest that
      the spatial distribution of myocyte interconnections and the molecular
      composition of gap junction channels may confer distinct conduction properties on
      specific tissues of the mammalian heart such as atrial and ventricular
      myocardium, and the nodes and bundles of the cardiac conduction system.

PMID- 8534899
TI  - Myocardial gap junction organization in ischemia and infarction.
AB  - Ischemia causes an increase in myocardial resistivity and a decrease in
      conduction velocity, thereby enhancing cardiac contractile dysfunction and
      arrhythmic tendency. Myocardial gap junctions, as principal determinants of
      conduction velocity, may, therefore, be expected to be deranged in ischemia.
      Despite a lack of consensus, attempts at correlating gap junction ultrastructural
      morphology with functional state have revealed the component connexons of gap
      junctions in freeze-fractured myocardium to be in multiple small hexagonal
      arrays, tending to become randomly distributed and compacted under uncoupling
      conditions. Further hypoxic uncoupling causes ultrastructural damage and a
      reduction in gap-junctional surface area. Immunohistochemical detection of
      connexin43 gap junctions in chronically ischemic non-infarcted human myocardium
      demonstrates a reduction in junctional surface area within a normal number of
      intercalated disks per myocyte, and with a normal distribution of junction sizes.
      In healed canine infarction there are smaller and fewer gap junctions in the
      fibrotic myocardium adjacent to infarcts, with reductions in overall gap
      junctional content and the proportion of side-to-side vs. end-to-end
      intercellular connections. Immunohistochemical examination of intact human
      ventricular myocardium shows the myocytes immediately abutting healed infarcts to
      have connexin43 gap junctions spread longitudinally over the cell surfaces, and
      not in discrete transversely orientated intercalated disks as in normal
      myocardium. Early after canine infarction, and before fibrotic healing, the
      connexin43 gap junctions in myocytes abutting the infarct show disorganization
      similar to that described in healed human infarcts, suggesting that this
      disturbance is an early pathophysiological cellular response, and not simply due
      to later fibrotic distortion. Such changes in gap-junctional organization in
      myocardial ischemia and infarction may be implicated in the elusive link between
      subcellular structure, contractile dysfunction and arrhythmogenesis.

PMID- 8534900
TI  - Quantitative junctional permeability measurements using the confocal microscope.
AB  - This paper describes the use of a photobleach method and confocal microscopy to
      compare the cell-to-cell transfer rate of 5,6 carboxyfluorescein in dissociated
      embryonic chick lens cells with those in the anterior epithelium of the whole
      embryonic chick lens. The average cell-to-cell transfer rates obtained were 7.9 x
      10(-3) sec-1 in the dissociated cells and 2.6 x 10(-3) sec-1 in the anterior
      epithelium in an intact lens.

PMID- 8534901
TI  - Gap junctions in blood forming tissues.
AB  - More than ten research groups have now reported the presence of gap junctions in
      blood-forming tissue or cultured cells. It is time to accept that these cell
      coupling structures are present in this tissue. To find out what they are doing
      here we need to develop appropriate experimental techniques. This review covers
      the particular problems of investigating direct cell-cell communication by gap or
      other junctions in undisturbed haemopoietic tissue. It then describes and
      assesses the published reports of haemopoietic gap junctions. Recently, in the
      author's laboratory, three means of increasing the number of gap junctions 50- to
      100-fold in mouse marrow have been described, as well as techniques for doing so
      in culture. There is a complete report of this work here. At present it is quite
      unclear what function gap junctions serve in blood-formation, perhaps it is some
      consolation that 30 years after their ultramicroscopic discovery it is also true
      for all other unexcitable tissues. Possibly the ability to up-regulate their
      expression in haemopoietic tissue will help us find out what their role is in
      blood formation.

PMID- 8534902
TI  - Gap junctions in the vertebrate retina.
AB  - The vertebrate retina is a highly laminated assemblage of specialized neuronal
      types, many of which are coupled by gap junctions. With one interesting
      exception, gap junctions are not directly responsible for the 'vertical'
      transmission of visual information from photoreceptors through bipolar and
      ganglion cells to the brain. Instead, they mediate 'lateral' connections,
      coupling neurons of a single type or subtype into an extended, regular array or
      mosaic in the plane of the retina. Such mosaics have been studied by several
      microscopic techniques, but new evidence for their coupled nature has recently
      been obtained by intracellular injection of biotinylated tracers, which can pass
      through gap junctional assemblies that do not pass Lucifer Yellow. This evidence
      adds momentum to an existing paradigm shift towards a population-based view of
      the retina, which can now be envisaged both as an array of semi-autonomous
      vertical processing modules, each extending right through the retina, and as a
      multi-layered stack of interacting planar mosaics, bearing some resemblance to a
      set of interleaved neural networks. Junctional conductance across mosaics of
      horizontal cells is known to be controlled dynamically with a circadian rhythm,
      and other dynamically-regulated conductance changes are also likely to make
      important contributions to signal processing. The retina is an excellent system
      in which to study such changes because many aspects of its structure and function
      are already well understood. In this review, we summarize the microscopic
      appearance, coupling properties and functions of gap junctions for each cell type
      of the neural retina, the regulatory properties that could be provided by
      selective expression of different connexin proteins, and the evidence for gap
      junctional coupling in retina development.

PMID- 8534903
TI  - Differential connexin distribution accommodates cardiac function in different
      species.
AB  - Using immunohistochemical staining, the distribution of connexin40 (Cx40) and
      connexin43 (Cx43) was studied in rat, guinea pig, porcine, bovine and human
      hearts. These species display differences in the degree of morphological
      differentiation of the conduction system. This study was performed in the
      anticipation that comparison of the distributions of Cx40 and Cx43 in young and
      adult specimens may provide clues as to the physiological role of connexins in
      the heart. To a large extent, the distribution patterns of Cx40 and Cx43 are
      comparable between species. In neonates and adults, Cx43 was immunolocalized
      throughout the working myocardium, but in the conduction system Cx43 was detected
      only after birth. Cx40 was found to appear slightly earlier in development than
      Cx43 and to disappear when levels of Cx43 became more abundant. This time course
      was seen in working myocardium and in the ventricular conduction system. Together
      these data suggest that expression of Cx40 induces or facilitates expression of
      Cx43, while abundant expression of Cx43 in turn leads to suppression of Cx40
      expression. The exceptions to this may represent blocks in this potential
      regulatory sequence. A second conclusion is that Cx40 and Cx43 containing gap
      junctions appear in the ventricular conduction system from distal to proximal and
      only after birth. This indicates that terminal differentiation of the conduction
      system occurs unexpectedly late in development.

PMID- 8534904
TI  - Gap junctions revealed by freeze-fracture electron microscopy.
AB  - Gap junctions provide the basis for the formation of elaborate networks of
      communication between cells in animal tissues. Electron microscopic examination
      of thin sections of plastic embedded gap junctions has provided valuable
      information on the anatomy and function of these remarkable structures. Freeze
      fracture electron microscopy, however, has made available unique vistas of gap
      junction-bearing intramembrane surface--surface previously inaccessible to the
      researcher's eyes. Data on population density, distribution, size, geometry of
      intramembrane particle packing, and structural responses of gap junction
      components to experimental manipulation are simply and easily obtained with
      freeze fracture. Recent developments of sophisticated protocols of
      immunocytochemistry as applied to freeze-fracture replicas further serve to
      reinforce the notion that freeze-fracture is a powerful tool for study of gap
      junctions. Molecular techniques of gap junction gene transfection promise to add
      a truly unique dimension to investigations of the broad spectrum of functional
      roles of gap junctions.

PMID- 8534905
TI  - Spatial organization of cardiac gap junctions can affect access resistance.
AB  - In the heart, gap junctions electrically couple myocytes together. Electron- and
      light-microscope-based analyses have revealed that cardiac gap junctions show a
      variety of organizational patterns. At the level of gap-junctional channel
      aggregates, freeze fracture has demonstrated diverse channel packing arrangements
      in the membranes of different myocardial tissues. Ultrastructural and
      immunohistochemical studies have shown variation and specialization in the 3
      dimensional spatial distribution of gap junctional contacts between different
      types of myocardial cells. Here, we estimate the access resistance of various
      configurations of gap junctions using physical principles and explore how certain
      of these specializations in gap-junctional organization may influence access
      resistance, a potentially important determinant of electrical conductance between
      coupled myocardial cells.

PMID- 8534906
TI  - Electron microscopic image analysis of cardiac gap junction membrane crystals.
AB  - Cardiac gap junctions play an important functional role in the myocardium by
      electrically coupling adjacent cells, thereby providing a low resistance pathway
      for cell-to-cell propagation of the action potential. Two-dimensional
      crystallization of biochemically isolated rat ventricular gap junctions has been
      accomplished by an in situ method in which membrane suspensions are sequentially
      dialyzed against low concentrations of deoxycholate and dodecyl-beta-D-maltoside.
      Lipids are partially extracted without solubilizing the protein, and the
      increased protein concentration facilitates two-dimensional crystallization in
      the native membrane environment. The two-dimensional crystals have a nominal
      resolution of 16 A and display plane group symmetry p6 with a = b = 85 A and
      gamma = 120 degrees. Projection density maps show that the connexons in cardiac
      gap junctions are formed by a hexameric cluster of alpha 1 connexin subunits.
      Protease cleavage of alpha 1 connexin from 43 to 30 kDa releases approximately
      13kDa from the carboxy-tail, and the projection density maps are not
      significantly altered. Uranyl acetate stain penetrates the ion channel, whereas
      phosphotungstic acid is preferentially deposited over the lipid regions. This
      differential staining can be used to selectively probe the central channel of the
      connexon and the interface between the connexon and the lipid. The hexameric
      design of alpha 1 connexons appears to be a recurring quaternary motif for the
      multigene family of gap junction proteins.

PMID- 8534907
TI  - Isolation of a novel association network in a polymer gel.

PMID- 8534908
TI  - The cytoplasmic tail domain of the vacuolar protein sorting receptor Vps10p and a
      subset of VPS gene products regulate receptor stability, function, and
      localization.
AB  - VPS10 of Saccharomyces cerevisiae encodes a type I transmembrane receptor protein
      required for the sorting of the soluble vacuolar hydrolase carboxypeptidase Y
      (CPY). To characterize the essential structural features and intercompartmental
      transport itinerary of the CPY receptor, we have constructed mutant forms of
      Vps10p that alter the carboxyterminal cytoplasmic tail of the protein. In
      addition, we have analyzed the effect these mutations as well as mutations in
      several VPS genes have on the function, stability, and localization of Vps10p.
      Although wild-type Vps10p is very stable over a 3-h chase period, overproduction
      of Vps10p results in PEP4-dependent degradation of the receptor.
      Immunofluorescence studies indicate that overexpressed receptor is delivered to
      the vacuole. A mutant form of Vps10p, in which 157 residues of the 164-residue
      cytoplasmic tail domain have been deleted, missorts CPY and is degraded rapidly.
      Additional mutations in the carboxy-terminus of Vps10p, including a deletion of a
      putative retention/recycling signal (FYVF), also result in CPY missorting and
      PEP4-dependent receptor instability. Because the cytoplasmic tail domain may
      interact with other factors, possibly VPS gene products, Vps10p stability was
      examined in a number of vps mutants. As was observed with the late Golgi protein
      Kex2p, Vps10p is unstable in a vps1 mutant. However, instability of Vps10p is
      even more severe in the class E vps mutants. Double mutant analyses demonstrate
      that this rapid degradation is dependent upon vacuolar proteases and a functional
      vacuolar ATPase. Fractionation studies of Vps10p in class E vps mutant strains
      indicate that the turnover of Vps10p occurs in a compartment other than the
      vacuole. These data are consistent with a model in which the cytoplasmic tail of
      Vps10p directs cycling of the receptor between a late Golgi sorting compartment
      and a prevacuolar endosome-like compartment, an exaggerated form of which is
      present in the vps class E mutants.

PMID- 8534909
TI  - Mutations in nucleolar proteins lead to nucleolar accumulation of polyA+ RNA in
      Saccharomyces cerevisiae.
AB  - Synthesis of mRNA and rRNA occur in the chromatin-rich nucleoplasm and the
      nucleolus, respectively. Nevertheless, we here report that a Saccharomyces
      cerevisiae gene, MTR3, previously implicated in mRNA transport, codes for a novel
      essential 28-kDa nucleolar protein. Moreover, in mtr3-1 the accumulated polyA+
      RNA actually colocalizes with nucleolar antigens, the nucleolus becomes somewhat
      disorganized, and rRNA synthesis and processing are inhibited. A strain with a ts
      conditional mutation in RNA polymerase I also shows nucleolar accumulation of
      polyA+ RNA, whereas strains with mutations in the nucleolar protein Nop1p do not.
      Thus, in several mutant backgrounds, when mRNA cannot be exported i concentrates
      in the nucleolus. mRNA may normally encounter nucleolar components before export
      and proteins such as Mtr3p may be critical for export of both mRNA and ribosomal
      subunits.

PMID- 8534910
TI  - Requirement for phosphorylation of cyclin B1 for Xenopus oocyte maturation.
AB  - Maturation-promoting factor, consisting of cdc2 protein kinase and a regulatory B
      type cyclin, is a universal regulator of meiosis and mitosis in eukaryotes. In
      Xenopus, there are two subtypes of B-type cyclins, designated B1 and B2, both of
      which are phosphorylated. In this study, we have investigated the biological
      significance of this phosphorylation for Xenopus cyclin B1 during meiotic
      maturation. We have used a combination of site-directed mutagenesis and
      phosphopeptide-mapping to identify serine residues 2, 94, 96, 101, and 113 as
      presumptive phosphorylation sites, and together these sites account for all
      cyclin B1 phosphorylation in oocytes before germinal vesicle breakdown (GVBD).
      Single Ser-->Ala mutants as well as multiple site mutants have been constructed
      and characterized. Phosphorylation of cyclin B1 appears to be required for
      Xenopus oocyte maturation, based on the significantly diminished ability of the
      quintuple Ala mutant to induce oocyte maturation. Furthermore, partial
      phosphorylation of these five sites is sufficient to meet this requirement.
      Phosphorylation of cyclin B1 is not required for cdc2 kinase activity, for
      binding to cdc2 protein, for stability of cyclin B1 before GVBD, or for
      destruction of cyclin B1 after GVBD or after egg activation. A quintuple Glu
      mutant was also constructed, with serine residues 2, 94, 96, 101, and 113 mutated
      to Glu. In contrast to the quintuple Ala mutant, the quintuple Glu mutant was
      able to induce oocyte maturation efficiently, and with more rapid kinetics than
      wild-type cyclin B1. These data confirm that phosphorylation, as mimicked by Ser-
      >Glu mutations, confers enhanced biological activity to cyclin B1. Possible roles
      of cyclin B1 phosphorylation are discussed that might account for the increased
      biological activity of the quintuple Glu mutant.

PMID- 8534911
TI  - Glucose-dependent turnover of the mRNAs encoding succinate dehydrogenase peptides
      in Saccharomyces cerevisiae: sequence elements in the 5' untranslated region of
      the Ip mRNA play a dominant role.
AB  - We have demonstrated previously that glucose repression of mitochondrial
      biogenesis in Saccharomyces cerevisiae involves the control of the turnover of
      mRNAs for the iron protein (Ip) and flavoprotein (Fp) subunits of succinate
      dehydrogenase (SDH). Their half-lives are > 60 min in the presence of a
      nonfermentable carbon source (YPG medium) and < 5 min in glucose (YPD medium).
      This is a rare example in yeast in which the half-lives are > 60 min in the
      presence of a nonfermentable carbon source (YPG medium) and < 5 min in glucose
      (YPD medium). This is a rare example in yeast in which the half-life of an mRNA
      can be controlled by manipulating external conditions. In our current studies, a
      series of Ip transcripts with internal deletions as well as chimeric transcripts
      with heterologous sequences (internally or at the ends) have been examined, and
      we established that the 5'-untranslated region (5' UTR) of the Ip mRNA contains a
      major determinant controlling its differential turnover in YPG and YPD.
      Furthermore, the 5' exonuclease encoded by the XRN1 gene is required for the
      rapid degradation of the Ip and Fp mRNAs upon the addition of glucose. In the
      presence of cycloheximide the nucleolytic degradation of the Ip mRNA can be
      slowed down by stalled ribosomes to allow the identification of intermediates.
      Such intermediates have lost their 5' ends but still retain their 3' UTRs. If
      protein synthesis is inhibited at an early initiation step by the use of a prt1
      mutation (affecting the initiation factor eIF3), the Ip and Fp mRNAs are very
      rapidly degraded even in YPG. Significantly, the arrest of translation by the
      introduction of a stable hairpin loop just upstream of the initiation codon does
      not alter the differential stability of the transcript in YPG and YPD. These
      observations suggest that a signaling pathway exists in which the external carbon
      source can control the turnover of mRNAs of specific mitochondrial proteins.
      Factors must be present that control either the activity or more likely the
      access of a nuclease to the select mRNAs. As a result, we propose that a
      competition between initiation of translation and nuclease action at the 5' end
      of the transcript determines the half-life of the Ip mRNA.

PMID- 8534912
TI  - Wortmannin blocks lipid and protein kinase activities associated with PI 3-kinase
      and inhibits a subset of responses induced by Fc epsilon R1 cross-linking.
AB  - We have investigated the effects of wortmannin, an inhibitor of
      phosphatidylinositol 3-kinase (PI 3-kinase), on antigen-mediated signaling in the
      RBL-2H3 mast cell model. In RBL-2H3 cells, the cross-linking of high affinity IgE
      receptors (Fc epsilon R1) activates at least two cytoplasmic protein tyrosine
      kinases, Lyn and Syk, and stimulates secretion, membrane ruffling, spreading,
      pinocytosis, and the formation of actin plaques implicated in increased cell
      substrate adhesion. In addition, Fc epsilon R1 cross-linking activates PI 3
      kinase. It was previously shown that wortmannin causes a dose-dependent
      inhibition of PI 3-kinase activity and also inhibits antigen-stimulated
      degranulation. We report that the antigen-induced synthesis of inositol(1,4,5)P3
      is also markedly inhibited by wortmannin. Consistent with evidence in other cell
      systems implicating phosphatidylinositol(3,4,5)P3 in ruffling, pretreatment of
      RBL-2H3 cells with wortmannin inhibits membrane ruffling and fluid pinocytosis in
      response to Fc epsilon R1 cross-linking. However, wortmannin does not inhibit
      antigen-induced actin polymerization, receptor internalization, or the actin
      dependent processes of spreading and adhesion plaque formation that follow
      antigen stimulation in adherent cells. Wortmannin also fails to inhibit either of
      the Fc epsilon R1-coupled tyrosine kinases, Lyn or Syk, or the activation of
      mitogen-activated protein kinase as measured by in vitro kinase assays.
      Strikingly, there is substantial in vitro serine/threonine kinase activity in
      immunoprecipitates prepared from Fc epsilon R1-activated cells using antisera to
      the p85 subunit of PI 3-kinase. This activity is inhibited by pretreatment of the
      cells with wortmannin or by the direct addition of wortmannin to the kinase
      assay, suggesting that PI 3-kinase itself is capable of acting as a protein
      kinase. We conclude that Fc epsilon R1 cross-linking activates both lipid and
      protein kinase activities of PI 3-kinase and that inhibiting these activities
      with wortmannin results in the selective block of a subset of Fc epsilon R1
      mediated signaling responses.

PMID- 8534913
TI  - The C. elegans sex-determining gene fem-2 encodes a putative protein phosphatase.
AB  - The genetic and molecular analysis of genes involved in the regulation of sex
      determination in Caenorhabditis elegans suggests that the gene fem-2 plays an
      important role in regulating a pathway transducing a non-cell-autonomous signal
      to a nuclear transcription factor. The wild-type fem-2 gene was cloned by
      identifying sequences from the C. elegans physical map that could restore normal
      Fem-2 function to homozygous mutant fem-2 transgenic animals. cDNA sequences
      mapping to the minimal rescuing region correspond to an open reading frame with a
      sequence similar to protein phosphatase 2C enzymes from systems as diverse as
      yeast, humans, and plants, but the alignments suggest that FEM-2 falls into a
      separate class of proteins than the canonical homologues. Several fem-2 mutant
      alleles were sequenced, and the mutations are predicted to cause protein changes
      consistent with their observed phenotypes, such as missense mutations in
      conditional alleles, and a nonsense mutation in a predicted null allele. This is
      the first evidence implicating phosphorylation and/or dephosphorylation as a
      control mechanism in C. elegans sex determination.

PMID- 8534914
TI  - Transient, lectin-like association of calreticulin with folding intermediates of
      cellular and viral glycoproteins.
AB  - The soluble, calcium-binding protein calreticulin shares high sequence homology
      with calnexin, a transmembrane chaperone of glycoprotein folding. Our experiments
      demonstrated that calreticulin, like calnexin, associated transiently with
      numerous newly synthesized proteins in the endoplasmic reticulum. The population
      of proteins that bound to calreticulin was partially overlapping with those that
      bound to calnexin. Hemagglutinin (HA) of influenza virus was shown to associate
      with both calreticulin and calnexin. Using HA as a model substrate, it was found
      that both calreticulin- and calnexin-bound HA corresponded primarily to
      incompletely disulfide-bonded folding intermediates and conformationally trapped
      forms. Binding of all substrates was oligosaccharide-dependent and required the
      trimming of glucose residues from asparagine-linked core glycans by glucosidases
      I and II. In vitro, alpha-mannosidase digestion of calreticulin-bound HA
      indicated that calreticulin was specific for monoglucosylated glycans. Thus,
      calreticulin appeared to be a lectin with similar oligosaccharide specificity as
      its membrane-bound homologue, calnexin. Both are therefore likely to play an
      important role in glycoprotein maturation and quality control in the endoplasmic
      reticulum.

PMID- 8534915
TI  - Schizosaccharomyces pombe zfs1+ encoding a zinc-finger protein functions in the
      mating pheromone recognition pathway.
AB  - We isolated the Schizosaccharomyces pombe zfs1 gene as a multicopy suppressor of
      the sterility caused by overexpression of a double-stranded RNase. The deduced
      zfs1 gene product of 404 amino acids showed similarity to a mouse growth factor
      inducible nuclear protein Nup475. Its C-terminal region carried two putative zinc
      fingers, both of which should be intact for the protein to be functional as the
      suppressor. This protein appeared to localize in nuclei. Disruption of zfs1 was
      not lethal but conferred deficiency in mating and sporulation. Activation of
      transcription in response to the mating pheromone signaling was greatly reduced
      in the zfs1-disrupted cells. The mating deficiency of the zfs1-disruptant was
      suppressed partially by overexpression of either gpa1, ras1, byr1, or byr2, which
      are involved in the transmission of the pheromone signal. Disruption of zfs1
      reduced both hypersensitivity of the ras1Val17 mutant to the mating pheromone and
      uncontrolled mating response caused by mutational activation of Gpa1, the G
      protein alpha subunit coupled to the mating pheromone receptors. However,
      overexpression of zfs1 could not bypass complete loss of function of either gpa1,
      ras1, byr1, or byr2. These observations indicate that the function of zfs1 is
      involved in the mating pheromone signaling pathway, and are consistent with its
      function being required to fully activate a factor in this pathway, either
      directly or indirectly.

PMID- 8534916
TI  - Redistribution of the CDK inhibitor p27 between different cyclin.CDK complexes in
      the mouse fibroblast cell cycle and in cells arrested with lovastatin or
      ultraviolet irradiation.
AB  - The cyclin-dependent kinase (CDK) inhibitor p27 binds and inhibits the kinase
      activity of several CDKs. Here we report an analysis of the behavior and partners
      of p27 in Swiss 3T3 mouse fibroblasts during normal mitotic cell cycle
      progression, as well as in cells arrested at different stages in the cycle by
      growth factor deprivation, lovastatin treatment, or ultraviolet (UV) irradiation.
      We found that the level of p27 is elevated in cells arrested in G0 by growth
      factor deprivation or contact inhibition. In G0, p27 was predominantly monomeric,
      although some portion was associated with residual cyclin A.Cdk2. During G1, all
      of p27 was associated with cyclin D1.Cdk4 and was then redistributed to cyclin
      A.Cdk2 as cells entered S phase. The loss of the monomeric p27 pool as cyclins
      accumulate in G1 is consistent with the in vivo and in vitro data showing that
      p27 binds better to cyclin.CDK complexes than to monomeric CDKs. In growing
      cells, the majority of p27 was associated with cyclin D1 and the level of p27 was
      significantly lower than the level of cyclin D1. In cells arrested in G1 with
      lovastatin, cyclin D1 was degraded and p27 was redistributed to cyclin A.Cdk2. In
      contrast to p21 (which is a p27-related CDK inhibitor and is induced by UV
      irradiation), the level of p27 was reduced after UV irradiation, but because
      cyclin D1 was degraded more rapidly than p27, there was a transient increase in
      binding of p27 to cyclin A.Cdk2. These data suggest that cyclin D1.Cdk4 acts as a
      reservoir for p27, and p27 is redistributed from cyclin D1.Cdk4 to cyclin A.Cdk2
      complexes during S phase, or when cells are arrested by growth factor
      deprivation, lovastatin treatment, or UV irradiation. It is likely that a similar
      principle of redistribution of p27 is used by the cell in other instances of cell
      cycle arrest.

PMID- 8534917
TI  - Vinblastine suppresses dynamics of individual microtubules in living interphase
      cells.
AB  - We have characterized the effects of vinblastine on the dynamic instability
      behavior of individual microtubules in living BS-C-1 cells microinjected with
      rhodamine-labeled tubulin and have found that at low concentrations (3-64 nM),
      vinblastine potently suppresses dynamic instability without causing net
      microtubule depolymerization. Vinblastine suppressed the rates of microtubule
      growth and shortening, and decreased the frequency of transitions from growth or
      pause to shortening, also called catastrophe. In vinblastine-treated cells, both
      the average duration of a pause (a state of attenuated dynamics where neither
      growth nor shortening could be detected) and the percentage of total time spent
      in pause were significantly increased. Vinblastine potently decreased dynamicity,
      a measure of the overall dynamic activity of microtubules, reducing this
      parameter by 75% at 32 nM. The present work, consistent with earlier in vitro
      studies, demonstrates that vinblastine kinetically caps the ends of microtubules
      in living cells and supports the hypothesis that the potent chemotherapeutic
      action of vinblastine as an antitumor drug is suppression of mitotic spindle
      microtubule dynamics. Further, the results indicate that molecules that bind to
      microtubule ends can regulate microtubule dynamic behavior in living cells and
      suggest that endogenous regulators of microtubule dynamics that work by similar
      mechanisms may exist in living cells.

PMID- 8534918
TI  - Functional expression of a vertebrate inwardly rectifying K+ channel in yeast.
AB  - We describe the expression of gpIRK1, an inwardly rectifying K+ channel obtained
      from guinea pig cardiac cDNA. gpIRK1 is a homologue of the mouse IRK1 channel
      identified in macrophage cells. Expression of gpIRK1 in Xenopus oocytes produces
      inwardly rectifying K+ current, similar to the cardiac inward rectifier current
      IK1. This current is blocked by external Ba2+ and Cs+. Plasmids containing the
      gpIRK1 coding region under the transcriptional control of constitutive (PGK) or
      inducible (GAL) promoters were constructed for expression in Saccharomyces
      cerevisiae. Several observations suggest that gpIRK1 forms functional ion
      channels when expressed in yeast. gpIRK1 complements a trk1 delta trk2 delta
      strain, which is defective in potassium uptake. Expression of gpIRK1 in this
      mutant restores growth on low potassium media. Growth dependent on gpIRK1 is
      inhibited by external Cs+. The strain expressing gpIRK1 provides a versatile
      genetic system for studying the assembly and composition of inwardly rectifying
      K+ channels.

PMID- 8534920
TI  - [The thoraco-lumbar junction. Orientation of zygapophyses, mamillary process and
      vertebral rotation].
AB  - The orientation of the zygapophyseal joints at the thoraco-lumbar level is an
      important factor involved in the axial rotation of the human spine. The
      functional role of the Mamillary Processes (MP) is unknown. This study was
      carried out on 55 adult dried spines. The aims were 1) to record the
      interzygapophyseal joint angles. 2) to determine morphological and functional
      angle types. 3) to correlate the various types and the corresponding MP lengths.
      4) to propose hypotheses about the MP role. There were 2 distinct morphotic types
      founded on 2 different populations of angles clearly visible on histograms at the
      T12 level and statistically detectable at the T11 and L1 levels. T11-T12-L1
      realized an homogeneous anatomical unit with 2 separate groups depending on the
      zygapophyseal joint orientations. A functional classification was also possible
      depending on the location of the geometric axial center of rotation. The
      "thoracic" type which center was on vertebral body. 95% of T10 vertebrae and 88%
      of T11 vertebrae belonged to the "thoracic" type whereas 97% of L1 ans 98% of L2
      belonged to the lumbar type. At the T12 level, we found 35% of "thoracic" type
      and 65% of "lumbar" type. Long MP were found on "lumbar" type vertebrae with
      little interzygapophyseal angles (p < 0.001). "Anatomical" types were not related
      to different MP lengths. On the contrary, the "functional" classification showed
      shorter MP on "thoracic" type vertebrae than on "lumbar" vertebrae (1.9 +/- 2.9
      mm vs 4.5 +/- 3 mm, p < 0.03). A large interzygapophyseal angle is known to
      enhance the axial rotation of the thoraco-lumbar junction. We infer that MP also
      play a role in axial rotation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534921
TI  - [An alternative to immunofluorescence on frozen tissue for the diagnosis of sub
      epidermal auto-immune bullous dermatosis].
AB  - The diagnosis of subepidermal auto-immune bullous dermatosis is usually based on
      immunofluorescence which demonstrates IgA, IgG, IgM or C3 on dermo-epidermal
      junction. However in some instance, this technique could not be performed. Here
      we report an alternative to immunofluorescence. It is a preembedding technique of
      immunolabelling using horseradish peroxidase, on fresh tissue without any
      freezing, before an inclusion in wax. So the observation of the labelling is
      possible with a standard microscope. This technique has been applied to 7
      patients with various sub-epidermal auto-immune bullous dermatosis whose
      diagnosis was confirmed elsewhere by immunoelectron microscopy. It was as
      specific and sensitive than immunofluorescence whatever the bullous dermatosis.

PMID- 8534922
TI  - [Anatomic description of the course of recurrent nerves in the rat].
AB  - The authors have performed an study of the origin, the course and the end of the
      recurrent nerves right and left in the rat. They have realize the microdissection
      in detail of the cervical and thoracic regions in order to made the photos the
      most significant in the recurrent nerves' description.

PMID- 8534919
TI  - Microtubule stability in budding yeast: characterization and dosage suppression
      of a benomyl-dependent tubulin mutant.
AB  - To better understand the dynamic regulation of microtubule structures in yeast,
      we studied a conditional-lethal beta-tubulin mutation tub2-150. This mutation is
      unique among the hundreds of tubulin mutations isolated in Saccharomyces
      cerevisiae in that it appears to cause an increase in the stability of
      microtubules. We report here that this allele is a mutation of threonine 238 to
      alanine, and that tub2-150 prevents the spindle from elongating during anaphase,
      suggesting a nuclear microtubule defect. To identify regulators of microtubule
      stability and/or anaphase, yeast genes were selected that, when overexpressed,
      could suppress the tub2-150 temperature-sensitive phenotype. One of these genes,
      JSN1, encodes a protein of 125 kDa that has limited similarity to a number of
      proteins of unknown function. Overexpression of the JSN1 gene in a TUB2 strain
      causes that strain to become more sensitive to benomyl, a microtubule
      destabilizing drug. Of a representative group of microtubule mutants, only one
      other mutation, tub2-404, could be suppressed by JSN1 overexpression, showing
      that JSN1 is an allele-specific suppressor. As tub2-404 mutants are also
      defective for spindle elongation, this provides additional support for a role for
      JSN1 during anaphase.

PMID- 8534923
TI  - [The arteries of the stomach].
AB  - In order to specify the gastric-arterial systematization, 65 fresh stomachs of
      adults deceased from non-gastro-duodenal causes, extracted by necropsy, allowed
      us to study the arteries of the stomach through the injection-corrosion technics.
      A selective injection for each arterial trunk has been made on 15 stomachs. This
      work allowed us to know better the arterial supply of the stomach and ut into
      obviousness important vascular anastomosis. While emphasizing on the substitute
      notion, the persons who wrote this summary describe regions poor in anastomosis,
      which correspond surgically with "critical" areas. They also emphasize how
      important it is to have an estimated score of the ischemia for gastric surgery,
      especially in the case of oeso-gastroplasty.

PMID- 8534924
TI  - [Diagnosis of congenital tracheo-bronchial malformations in the newborn and
      infant].
AB  - Diagnosis endoscopy in congenital tracheo-bronchial abnormalities. High quality
      of anesthesia and efficiency of light sources and optical systems, now allow safe
      examination of upper respiratory tract and ability to give very precise
      informations in neonates and infants. Endoscopy now is then an essential
      procedure for diagnostic of congenital anomalies of respiratory tract. The
      necessary conditions for a safe examination and the necessity of complete
      exploration are exposed as well as endoscopic aspects of various congenital
      anomalies.

PMID- 8534925
TI  - New aspects on the topography of the tendon of the long head of the biceps
      brachii muscle. One more stabilizer factor of the shoulder joint.
AB  - There are little variations in descriptions on the origin of the tendon of the
      long head of the biceps brachii muscle, in the classical text books of Anatomy.
      Most authors define as the main origin of the tendon of the long head of the
      biceps brachii muscle, the supraglenoid tubercle and adjoining part of the
      glenoid labrum of the scapula. In the present study we found that the origin of
      the tendon of the long head of the biceps brachii muscle extended towards almost
      the whole periphery of the glenoid cavity on the glenoid labrum except from a
      small area near to the supraglenoid tubercle.

PMID- 8534926
TI  - Fractionation of Cremophor EL delineates components responsible for plasma
      lipoprotein alterations and multidrug resistance reversal.
AB  - Treatment of cancer patients with 3-h infusions of taxol formulated with
      Cremophor EL resulted in a marked decrease in the electrophoretic mobility of all
      plasma lipoproteins. Cremophor was fractionated by reverse-phase chromatography
      to determine which components were responsible for this behavior. Effects of
      different Cremophor fractions on reversal of multidrug resistance, amino acid
      transport, and cytotoxicity also were evaluated using murine leukemia cells in
      culture. Lipoprotein alterations were caused by Cremophor components of
      intermediate hydrophobicity, which also antagonized amino acid transport and
      decreased viability of murine leukemia cells. Cremophor components responsible
      for reversal of multidrug resistance were of greater hydrophobicity. The
      lipoprotein-altering components of Cremophor could be selectively removed without
      affecting either taxol solubilization or multidrug-resistant reversal.

PMID- 8534927
TI  - Difloxacin reverses multidrug resistance in HL-60/AR cells that overexpress the
      multidrug resistance-related protein (MRP) gene.
AB  - In this study, we have examined the in vitro chemosensitizing activity of
      difloxacin, a quinolone antimicrobial agent, in the multidrug-resistant human
      myeloid leukemia HL-60/AR cell line. HL-60/AR cells were found to overexpress
      multidrug resistance-associated protein (MRP) mRNA as compared to HL-60 cells.
      Difloxacin, in a concentration-dependent manner, increased the sensitivity of HL
      60/AR cells to daunorubicin, adriamycin, and vincristine, and partially corrected
      the altered drug transport. In addition, difloxacin corrected subcellular
      distribution of adriamycin by inducing redistribution of the drug from the
      perinuclear region to the nucleus in HL-60/AR cells. The chemosensitizing effect
      of difloxacin was observed at clinically achievable concentrations. We conclude
      that difloxacin is an effective chemosensitizer of MRP-associated multidrug
      resistant tumor cells and is a potential candidate for clinical use to reverse
      multidrug resistance.

PMID- 8534928
TI  - Suramin blocks binding of interleukin-4 to its receptors on human tumor cells and
      interleukin-4-induced mitogenic response.
AB  - Suramin, a polysulphonated naphthylurea, has antiproliferative, anticancer, and
      anti-HIV activities and has been shown to prevent binding of a variety of growth
      factors to their respective receptors. In the current study we have investigated
      the effects of suramin on binding of interleukin-4 (IL-4) to its receptors and IL
      4-induced biological response. We found that suramin prevented the binding of
      125I-labeled IL-4 to its receptor in a dose-dependent manner. The concentration
      of suramin that caused 50% inhibition of IL-4 binding (IC50) ranged between 55
      and 70 microM. This effect was observed on two human renal cell carcinoma cell
      lines (PM-RCC and WS-RCC), a human T lymphoma cell line (H9), and a human
      premyeloid cell line (TF-1). Cross-linking experiments provided direct evidence
      that suramin prevented binding of 125I-labeled IL-4 to its receptors.
      Radiolabeled IL-4 specifically cross-linked with major proteins of approximately
      145 and 65-70 kDa in both PM-RCC and H9 cell lines. Suramin prevented cross
      linking to both affinity cross-linked IL-4 binding proteins. Gel filtration
      results indicated that suramin caused aggregation of 125I-labeled IL-4. Suramin
      had a cytostatic rather than cytotoxic effect on H9 cells, and it inhibited IL-4
      induced proliferation of TF-1 cells. These data indicate that suramin may be a
      useful drug in the abrogation of IL-4-induced effects, and this property should
      be further explored in IL-4-mediated pathologic states.

PMID- 8534930
TI  - Difference between the resistance mechanisms of aclacinomycin- and adriamycin
      resistant P388 cell lines.
AB  - Aclacinomycin (ACR) is an anthracycline anticancer drug that shows marked effects
      in Adriamycin (ADM)-resistant tumors. ADM, however, is not effective against ACR
      resistant tumor cells. When tumor cells acquire resistance to ACR, though the
      resistance is not easily acquired, they show strong cross-resistance to ADM. To
      study the mechanism underlying these phenomena, we studied the resistance
      mechanism of ACR- and ADM-resistant P388 leukemia cells. The P388/ACR cells
      showed 4.9- and 100-fold resistance to ACR and ADM, respectively, whereas the
      P388/ADM cells showed respectively 2.0- and 270-fold resistance. Both P388/ACR
      and P388/ADM cells expressed large amounts of P-glycoprotein, and the amount was
      3-fold higher in the P388/ACR than in the P388/ADM cells. As a result, the
      accumulation of vincristine and ADM were greatly reduced in P388/ACR and P388/ADM
      cells, as compared with the parental P388 cells. The accumulation of ACR,
      however, was moderately reduced in both the resistant cell lines. ACR
      accumulation in P388/ACR and P388/ADM cells was reduced to respectively 37 and
      64% of the level in P388 cells. The amount and the activity of topoisomerase II
      were comparable in P388 and P388/ACR cells, but they were reduced in P388/ADM
      cells. Consequently, the formation of protein (topoisomerase II)-DNA cross-links
      induced by a topoisomerase II inhibitor was more prominent in the P388 and
      P388/ACR nuclei than in the P388/ADM nuclei. Notably, ACR could reduce the
      protein-DNA cross-links equally in the nuclei of P388, P388/ACR, and P388/ADM
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534929
TI  - Antiangiogenic treatment (TNP-470/minocycline) increases tissue levels of
      anticancer drugs in mice bearing Lewis lung carcinoma.
AB  - Although the antiangiogenic agent TNP-470 does not, in general, increase the
      cytotoxicity of anti-cancer therapies in cell culture, the antiangiogenic agents
      TNP-470 and minocycline individually and especially in combination have been
      shown to increase the tumor growth delay produced by several standard cytotoxic
      therapies in the Lewis lung carcinoma. In an effort to understand the mechanism
      by which the antiangiogenic agent combination TNP-470/minocycline potentiates the
      antitumor activity of cytotoxic therapeutic agents in vivo, the biodistribution
      of [14C]-cyclophosphamide and cis-diamminedichloroplatinum(II) was determined 6 h
      after cytotoxic drug administration in animals bearing Lewis lung carcinoma
      pretreated with TNP-470/minocycline and in animals without pretreatment. Higher
      levels of 14C and platinum were found in 9 tissues (including tumor) except blood
      in animals pretreated with TNP-470/minocycline. The increased drug levels in the
      tumors may be sufficient to account for the increased tumor growth delays
      observed previously. DNA alkaline elution of tumors from animals pretreated with
      TNP-470/minocycline showed increased DNA cross-linking by both cyclophosphamide
      and cis-diamminedichloroplatinum(II). The possible implications of these results
      are discussed.

PMID- 8534932
TI  - Reference listings in cancer research.

PMID- 8534931
TI  - Liposomal muramyl tripeptide upregulates adhesion molecules on the surface of
      human monocytes.
AB  - We previously demonstrated that liposome-encapsulated muramyl tripeptide
      phosphatidylethanolamine (L-MTP-PE), a biologic response modifier now undergoing
      phase III clinical trial in osteosarcoma, upregulated monocyte expression of
      several cytokines' mRNA and the subsequent production of these proteins. In the
      present work, we investigated whether L-MTP-PE upregulated adhesion molecules on
      the surface of normal human monocytes. Flow-cytometric analysis showed that
      several subunits of the integrins, including alpha L, alpha 5, and beta 1
      subunits, and intercellular adhesion molecule-1 on the monocytes were upregulated
      following their stimulation with 2 micrograms/ml L-MTP-PE for 24 h. Anti-alpha L
      antibodies blocked monocyte-mediated tumor cell killing stimulated by L-MTP-PE.
      We conclude that L-MTP-PE also stimulates the increase of several molecules on
      the monocyte cell surface. These adhesion molecules may contribute to the
      increased activation of monocyte-mediated tumor cell killing seen following L-MTP
      PE exposure.

PMID- 8534933
TI  - Cytotoxic potential of monoalkylation products between mitomycins and DNA:
      studies of decarbamoyl mitomycin C in wild-type and repair-deficient cell lines.
AB  - Hypoxic regions in solid neoplasms have been associated with tumor recurrence and
      resistance to several cancer treatment modalities including radiation therapy.
      Various strategies have been designed to target these resistant cells, including
      the use of the bioreductive alkylating agent mitomycin C (MC), which exerts
      preferential cytotoxicity under hypoxic conditions in most cell lines. Analyses
      of the mechanism of action of MC indicate that this drug can form cross-links
      with DNA; it is currently thought that this bisadduct is the critical lesion
      responsible for inhibiting DNA synthesis. Computer-generated models suggest that
      the MC adduct fits snugly into the minor groove of B-DNA without imposing major
      distortion on the structure of the DNA molecule. To gain additional insight into
      the role of cross-linkage in the cytotoxicity of MC, we studied the analogue,
      decarbamoyl mitomycin C (DMC). The structure of DMC is identical to that of MC
      with the exception of the substitution of the carbamoyl group at the C-10
      position by a nonalkylating hydroxyl group (-OH); this alteration would be
      expected to prevent DMC from forming bisadducts with DNA. In chemical systems,
      DMC produces only DNA monoadducts. If indeed it is the MC-DNA cross-links which
      are responsible for cell kill, one would predict DMC to be less cytotoxic than
      MC. However, tissue culture studies using DMC revealed that DMC is at least as
      toxic as MC to EMT6 mouse mammary tumor cells and to wild-type AA8 Chinese
      hamster ovary (CHO) cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8534934
TI  - What is new in fixed drug eruption?

PMID- 8534935
TI  - Keratosis lichenoides chronica: the centenary of another Kaposi's disease.
AB  - In 1895, Kaposi used the term 'lichen ruber acuminatus verrucosus et reticularis'
      to describe the case of a 27-year-old woman with a linear, warty lichenoid
      eruption. We have reviewed the literature and found 50 cases, of which only 40
      had common features reminiscent of the original description of Kaposi. These
      'authentic' cases of keratosis lichenoides chronica (KLC) showed strong clinical
      and histological similarity, a uniformity indicating that KLC is an entity and is
      distinct from lichen planus. KLC may be associated with internal diseases such as
      glomerulonephritis and lymphoproliferative disorders.

PMID- 8534936
TI  - Lyme disease in Japan. Analysis of Borrelia species using rRNA gene restriction
      fragment length polymorphism.
AB  - BACKGROUND: Lyme disease is sporadically observed in Japan since the first report
      in 1987. We have experienced 19 cases of Lyme disease. In 12 out of 13 trials we
      succeeded in isolating Borrelia strains (JEM1-12) from erythema migrans (EM)
      lesions. Recently, Borrelia burgdorferi sensu lato was classified into at least
      three distinct subgroups, B. burgdorferi sensu stricto, B. garinii and B.
      afzelii. OBJECTIVE: In order to characterize Lyme disease in Japan, we summarized
      the clinical features of our cases and investigated the nature of the isolated
      Borrelia strains. METHODS: The 12 Borrelia strains were analyzed by restriction
      fragment length polymorphism (RFLP) of ribosomal RNA gene. RESULTS: Most of our
      19 patients were in stage I with EM as the main clinical manifestation. RFLP
      analysis using 12 strains isolated from the patients indicated that 8 strains
      (group IV, V) were different from the three aforementioned genospecies.
      CONCLUSION: Clinical data from the present study substantiate the view that
      Japanese Lyme disease has a relatively milder course. We speculate that this may
      be related to the specific Borrelia strains in Japan.

PMID- 8534937
TI  - Cost-effectiveness of surveillance of stage I melanoma. A retrospective appraisal
      based on a 10-year experience in a dermatology department in France.
AB  - BACKGROUND: There is no agreement about surveillance after resection of a stage I
      melanoma. OBJECTIVE: We assessed the cost-effectiveness of this surveillance.
      METHODS: Out of 912 patients with stage I (and Clark's level > or = II) melanoma
      examined from 1981 to 1991, only 528 were regularly followed in our department.
      RESULTS: 115 out of 528 relapsed; 33% were detected by the patient himself, 16%
      by the referring physician and 39% were detected in our department. Chest X-ray
      or abdomen ultrasonography revealed only 10% of relapses; CT scans were useless.
      There was a huge gap between the cost-effectiveness of clinical examinations and
      radiology. The time between relapse and the last check-up in our department was
      less than 4 months in one third of the metastases. CONCLUSIONS: In stage I
      melanoma, only clinical examination is really cost-effective in the detection of
      metastases. However, many metastases are likely to become prominent between two
      examinations if patients are examined less than 3 times a year. A progressive
      decrease in frequency is thus not advisable, until the risk is considered low
      enough to stop follow-up.

PMID- 8534938
TI  - Antiphospholipid antibodies and anetoderma: are they associated?
AB  - BACKGROUND: Macular atrophy or anetoderma is a rare skin disease of unknown
      pathogenesis, characterised by wrinkled or flaccid skin. OBJECTIVE: The finding
      of anetoderma in 5 patients followed up because of false-positive seroreactions
      of syphilis prompted us to study the occurrence of antiphospholipid (aPL)
      antibodies in anetoderma. METHODS: 14 unselected patients with primary anetoderma
      (PA) were collected from hospital records and clinical, immunological and
      histological findings were compared in the two patient groups. RESULTS: Of the 5
      patients, 3 fulfilled the criteria for antiphospholipid syndrome. In two cases,
      it was secondary to systemic lupus erythematosus (SLE). Of the 14 PA patients 1
      had aPL antibodies and 4 had borrelia antibodies. Two patients had thyroid
      antibodies; 1 of them developed SLE. In several biopsy specimens, microthromboses
      were seen in both patient groups. CONCLUSION: On the basis of this study and our
      previous findings, it seems that anetoderma is more often associated with aPL
      positive SLE or lupus-like disease than with aPL-negative disease. Immunological
      mechanisms play an important role in both primary and secondary anetoderma. The
      meaning of false-positive serological tests for syphilis or borrelia and aPL
      antibodies is not clear, but they may be reacting to some still unidentified
      antigen. Probably, various systemic as well as local inflammatory and non
      inflammatory processes, e.g. microthromboses, can trigger anetoderma via still
      unknown pathomechanisms.

PMID- 8534939
TI  - The CHILD nevus: a distinct skin disorder.
AB  - BACKGROUND: The CHILD syndrome is characterized by an ichthyosiform and
      inflammatory nevus showing a strikingly unilateral arrangement. No particular
      name has so far been given to this nevus, which is why this skin disorder has
      been described under various inappropriate terms such as epidermal nevus,
      inflammatory linear verrucous epidermal nevus (ILVEN), unilateral ichthyosiform
      erythroderma, unilateral ichthyosis or verruciform xanthoma. OBJECTIVE: In order
      to avoid such confusion and to make it easier for clinicians to recognize this
      skin disease, a new name should be given to this disorder, and the diagnostic
      criteria should be delineated. METHOD: The term CHILD nevus is proposed and the
      distinctive clinical, histopathological and ultrastructural features of this
      disorder are described. RESULTS: A comprehensive clinical and genetic comparison
      shows that the CHILD nevus can be distinguished from all other types of epidermal
      nevi by characteristic features such as ptychotropism, waxy yellowish scaling, a
      unique lateralization pattern showing both diffuse and linear involvement and the
      presence of foamy histiocytes in the papillae ('verruciform xanthoma').
      Contrasting with all other epithelial nevi, the CHILD nevus is an inherited X
      linked dominant, male-lethal trait. CONCLUSION: This nevus represents a separate
      cutaneous entity. Future clinical research will probably show that the underlying
      gene defect often manifests itself as an isolated skin disorder. Such cases
      should no longer be confused with ILVEN. Recognition of this particular skin
      disorder is important for genetic counseling because a woman showing an isolated
      CHILD nevus has an increased risk of giving birth to a daughter suffering from a
      complex congenital disorder, the CHILD syndrome.

PMID- 8534940
TI  - Tyrosine phosphorylation in psoriatic T cells is modulated by drugs that induce
      or improve psoriasis.
AB  - BACKGROUND: The induction of protein tyrosine kinases (PTKs) is known to be a key
      element in the activation of lymphocytes. OBJECTIVE: Because immunologic
      mechanisms are important in the pathogenesis of psoriasis, we examined the time
      course of tyrosine-phosphorylated proteins (p-tyr) as a marker for cellular PTK
      activity in phytohemagglutinin (PHA)-stimulated T cells of psoriatic patients and
      healthy controls. METHODS AND RESULTS: PHA-stimulated T cells from both groups
      expressed peaks of p-tyr after 15 min and 4 h. In T cells from psoriatics, the 15
      min peak was smaller but the 4-hour peak reached an enormous maximum, which was
      270% higher than the basic p-tyr value. PHA-stimulated T cells were additionally
      treated with psoriasis-provoking drugs (lithium, chloroquine, propranolol and
      ethanol) and the two immunosuppressive drugs cyclosporin A and FK 506. Lithium
      and propranolol were able to increase the p-tyr level after 15 min in PHA
      stimulated T cells from psoriatics in contrast to controls. Chloroquine and
      ethanol did not have a significant effect on T cells of both groups. CsA markedly
      diminished the phosphorylation of intracellular tyrosines in T cells of
      psoriatics and controls, whereas FK 506 diminished the p-tyr level in controls
      only slightly. CONCLUSION: We have characterized important differences in p-tyr
      phosphorylation activities of psoriatic T cells compared to controls. This could
      be a hint to explain the known abnormalities of psoriatic T cells.

PMID- 8534942
TI  - Adjuvant therapy of stage IIIb melanoma with interferon alfa-2b: clinical and
      immunological relevance.
AB  - BACKGROUND: The poor prognosis of stage IIIb melanoma (5-year survival: 36%)
      shows the need for effective adjuvant therapy to prolong disease-free survival.
      OBJECTIVE: The feasibility and efficacy of interferon alfa-2b (IFN-alpha) therapy
      in stage IIIb melanoma patients was investigated. METHODS: alpha-IFN was given at
      a dose of 3 MU i.m. three times a week to 50 patients. Clinical and immunological
      controls were carried out. RESULTS: The median follow-up was 43 months (range 5
      84). Median survival was 43 months and median disease-free survival 39 months.
      Overall 5-year survival (62%) was higher than that reported in the literature to
      date. A significant increase of circulating CD56+ and DR+ lymphocytes after
      therapy was more evident in disease-free patients than in those with progressing
      disease. CONCLUSIONS: Adjuvant IFN-alpha therapy in stage IIIb melanoma patients
      is well tolerated and seems to increase survival. However, multicenter randomized
      trials are needed to confirm these preliminary findings.

PMID- 8534941
TI  - Effects of calcitriol on fibroblasts derived from skin of scleroderma patients.
AB  - BACKGROUND: Scleroderma is a fibrotic disorder of unknown etiology that is
      characterized by excessive collagen synthesis and its deposition in the skin and
      various internal organs. OBJECTIVE: To examine whether an overproduction of
      extracellular matrix molecules is a result of either increased fibroblast
      proliferation or increased collagen synthesis. As results of clinical trials with
      1,25-dihydroxyvitamin D3 (calcitriol) have suggested beneficial effect in the
      treatment of scleroderma patients, the effects of calcitriol on fibroblasts
      derived from scleroderma and normal skin has been examined as well. METHODS:
      Cultures of fibroblasts were established from biopsies from involved and
      uninvolved skin of scleroderma patients and from skin of healthy subjects, and
      compared with respect to proliferation, collagen synthesis and collagen lattice
      contraction. RESULTS: No significant differences in cell proliferation and in the
      extent of fibroblast-induced collagen lattice contraction have been found between
      scleroderma patients exhibited a disorganized growth pattern in a monolayer
      culture in contrast to normal fibroblasts. Collagen synthesis tends to be higher
      in scleroderma fibroblasts as compared with controls. Calcitriol exerted an
      antiproliferative and antisynthetic effect on fibroblasts, which, however, did
      not discriminate healthy fibroblasts from fibroblasts derived from involved or
      uninvolved scleroderma plaques. CONCLUSIONS: Our findings suggest that collagen
      accumulation may not result from increased proliferation or altered dynamic
      properties of fibroblasts in a scleroderma lesion but from increased collagen
      biosynthesis. We additionally found that calcitriol does not selectively affect
      scleroderma fibroblasts.

PMID- 8534943
TI  - Cost reduction of skin biopsy and surgical instrumentation.
AB  - Saving the physicians time is very desirable in rendering first-rate
      dermatological service at lower cost. The aim is to reduce surgical
      instrumentation during skin biopsy procedures and follow-up visits. A combined
      instrument is used to obtain skin biopsies from 100 patients, and gelatin sponge
      plugs are used in hemostasis and to assist healing of the biopsy wound site. Skin
      biopsy samples are obtained simply and with ease, and, as the tissue sample is
      handled minimally, it appears to be more intact and less distorted in comparison
      to the usual procedure. Skin biopsy samples can be obtained with the combined
      instrument in a more cost-effective manner with savings of the physician's time
      and less instrumentation.

PMID- 8534944
TI  - Dermatomyositis with follicular hyperkeratosis.
AB  - We report 2 cases of dermatomyositis with follicular hyperkeratosis (FHK) in
      children. They occurred in a 10-year-old Vietnamese girl and a 9-year-old
      Caucasian boy. The girl's FHK disappeared after 2 months of treatment. The boy
      presented, 15 months after the onset of his dermatomyositis, with a generalised
      FHK which lasted for 6 months. FHK can appear before, during or after
      dermatomyositis. It is more often generalized but can be localised. Erector pili
      myositis and ostial hyperkeratosis may be the explanation. The prognostic value
      of FHK in dermatomyositis is unknown. This manifestation, initially considered to
      be more frequent in the Far East, is not as rare in Western countries as the few
      reported cases suggest.

PMID- 8534945
TI  - Pleomorphic fibroma on the scalp.
AB  - We present the eleventh case of benign pleomorphic fibroma arising on the scalp
      in a young Korean woman. Histopathologically these lesions were characterized by
      a polypoid or dome-shaped cutaneous fibrous mass with sparse cellularity but
      striking nuclear atypia and rare mitotic figures. They all showed benign clinical
      behavior, despite these histopathological findings.

PMID- 8534946
TI  - Milium-like syringoma in the perianal region.
AB  - We report a case of syringoma clinically presenting as milia in the perianal
      region. Milium-like syringoma is an unusual clinical variant of the tumor, and
      this is, to our knowledge, the first reported case occurring perianally.

PMID- 8534947
TI  - Cheilitis granulomatosa treated with metronidazole.
AB  - Cheilitis graunulomatosa (CG) is a chronic inflammatory disorder of unknown
      etiology. We report the case of a patient with CG who has successfully been
      treated with metronidazole.

PMID- 8534948
TI  - Verruciform xanthoma in a psoriatic patient under PUVA therapy.
AB  - A patient with psoriasis vulgaris developed verruciform xanthoma (VX) on the
      scrotum during psoralen photochemotherapy (PUVA). Although it is uncertain
      whether VX was induced by PUVA therapy, we report the first case of VX which
      appeared in a patient with psoriasis during PUVA therapy. We speculate that UV
      light may be one of the etiologic factors triggering VX in this case.

PMID- 8534949
TI  - Eosinophilic pustular folliculitis: successful treatment with interferon-alpha.
AB  - Eosinophilic pustular folliculitis (Ofuji's disease) is a rare skin disease of
      unknown etiology characterized by infiltrated circinate plaques with sterile
      follicular pustules in primarily seborrheic areas. Several therapeutic regimens
      have been reported to control the disease with inconsistent results. We here
      report on a patient with Ofuji's disease, who was successfully treated with
      interferon-alpha 2b.

PMID- 8534950
TI  - Retroauricular bilateral 'milia en plaque'.
AB  - A 49-year-old Caucasian female with multiple whitish granules within an
      erythematous plaque in her right retroauricle area is described. Histology was
      consistent with epidermal cysts. After 1 year, a group of similar granules
      occurred behind the left auricle. This is the second reported case of 'milia en
      plaque' with bilateral distribution.

PMID- 8534951
TI  - 'Milia en plaque' in the supraclavicular area.
AB  - 'Milia en plaque' is an unusual skin disease. Up to date only 6 cases have been
      reported, and all of them were located in the retro-auricular area. We report
      herein the first case of milia en plaque developed in the supraclavicular area.
      The absence of a known aetiologic factor in contrast to the previously published
      cases suggests that the present case belongs to the group of primary milia.

PMID- 8534952
TI  - Keratosis lichenoides chronica: a pediatric case.
AB  - Keratosis lichenoides chronica (KLC) is a rare chronic disorder of keratinization
      characterized by lichenoid hyperkeratotic papules arranged in a linear pattern,
      erythematosquamous plaques and seborrhea-like dermatitis on the face. Adults
      between 20 and 50 years of age are usually affected, but the disease is very
      uncommon in childhood. Our purpose was to study the clinical and histopathologic
      findings and course of KLC in one pediatric case. Detailed clinical data were
      studied. Two punch biopsies were performed and histopathologic features were
      compared with those of other reported cases of KLC. In our patient, a 4-year-old
      boy, the clinical features of the lesions did not deviate notably from those of
      other cases of KLC. The histologic pattern of the papules was typical of KLC,
      while that of the erythematosquamous plaques showed some dyskeratotic
      keratinocytes. The histologic pattern of the erythematosquamous lesions is
      peculiar in our case, whereas only a nonspecific pattern is reported in the
      literature. The papular and erythematosquamous lesions showed similar
      histopathologic features suggesting that they could be different degrees of
      evolution of the same lesion.

PMID- 8534953
TI  - Follicular accentuation of leukocytoclastic vasculitis in an HIV-infected
      patient.

PMID- 8534954
TI  - Papular-purpuric gloves-and-socks syndrome related to cytomegalovirus infection.

PMID- 8534955
TI  - Fixed drug eruption secondary to ondansetron.

PMID- 8534956
TI  - Morphology, biology and biochemistry of cobalamin- and folate-deficient bone
      marrow cells.
AB  - B12- or folate-deficient haemopoietic cells display abnormalities in their
      morphology under both the light and electron microscope, their cell kinetics and
      their capacity to synthesize protein. These abnormalities are maximal in the last
      dividing cell class and in non-dividing cells, presumably because B12 and folate
      uptake is largely confined to the most immature erythroid and granulocyte
      precursors. In patients with moderate or severe anaemia due to B12 or folate
      deficiency, erythropoiesis is markedly ineffective; intramedullary cell death
      occurs mainly in the early and late polychromatic megaloblasts. The damaged
      erythroblasts appear to display neoantigens or normally-hidden antigens at their
      cell surface and these react with naturally occurring antibodies. The opsonised
      erythroblasts are then recognised by macrophages via their IgG-Fc receptors and
      phagocytosed. Marrow cells from B12- or folate-deficient patients show a
      subnormal suppression of 3H-thymidine incorporation after pre-incubation with
      nonradioactive deoxyuridine, suggesting that such cells suffer from an impairment
      of the 5,10-methylene-THF-dependent methylation of deoxyuridylate to thymidylate.
      However, the exact mechanism by which B12 deficiency causes a reduced supply of
      this folate coenzyme is uncertain. Methylcobalamin is required for the 5-methyl
      THF-dependent methylation of homocysteine to methionine and an impairment of this
      reaction will result in both reduced conversion of 5-methyl-THF to THF and in
      reduced methionine synthesis. There is controversy as to whether the reduced
      supply of THF or methionine is responsible for the reduced availability of 5,10
      methylene-THF. Currently, the balance of evidence favours the hypothesis that the
      reduced supply of methionine leads to reduced synthesis of formyl-THF and,
      eventually, of 5,10-methylene-THF. Despite the evidence for impaired thymidylate
      synthesis, the duration of the S phase of megaloblasts appears to be normal or
      only modestly increased. Data on rates of DNA strand elongation are inconsistent,
      with subnormal rates reported in PHA-stimulated B12- or folate-deficient
      lymphocytes and normal rates in B12- or folate-deficient bone marrow
      cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8534957
TI  - DNA damage in folate deficiency.
AB  - Folate deficiency significantly increases uracil content and chromosome breaks
      (as measured by micronucleated cells) in human leukocyte DNA. Folate
      supplementation reduces both the uracil content of DNA and the frequency of
      micronucleated cells, indicating that uracil misincorporation may play a
      causative role in folate deficiency-induced chromosome breaks. A calculation is
      presented to explain how the levels of uracil found in DNA could cause chromosome
      breaks. Based on this calculation, the frequency of uracil repair events that
      might result in double-strand DNA breaks increases by 1752-fold. These results
      are consistent with clinical and epidemiological evidence linking folate
      deficiency to DNA damage and cancer.

PMID- 8534958
TI  - The biochemical basis of the neuropathy in cobalamin deficiency.
AB  - The pathogenesis of the neuropathy associated with vitamin B12 deficiency
      (subacute combined degeneration (SCD)) is now thought to be related to
      interference with the methylation reactions in the CNS. The methylation reactions
      are processed by S-adenosylmethionine (SAM), which is controlled by its product,
      S-adenosylhomocysteine (SAH). The relationship of these two compounds is termed
      the methylation ratio. It has been demonstrated that if the ratio falls, the
      methylation reactions are inhibited leading to a state of CNS hypomethylation.
      The ratio can fall either due to a rise in SAH or a fall in SAM. It is suggested
      that for clinical signs to develop in animals who are susceptible to the lesion,
      both events are usually required. Inhibition of the vitamin B12-dependent enzyme,
      methionine synthase, leads to a rapid fall in the ratio in the CNS, since unlike
      other organs such as the liver, it does not have an alternative method of re
      methylating homocysteine to maintain the endogenous synthesis of SAM. The supply
      of methyl groups necessary for the re-methylation reactions is controlled by a
      series of enzymes, which include methionine synthase. The inborn errors of
      metabolism that produce deficiency or impairment of these enzymes are described.
      Neurological syndromes associated with deficiency of these enzymes have close
      associations with SCD. The other clinical evidence and animal experiments that
      support this hypothesis are also described.

PMID- 8534959
TI  - Transcobalamin II and the membrane receptor for the transcobalamin II-cobalamin
      complex.
AB  - Transcobalamin II is a plasma protein that binds vitamin B12 (cobalamin) as it is
      absorbed in the terminal ileum and distributes it to tissues. The circulating
      transcobalamin II-cobalamin complex binds to receptors on the plasma membrane of
      tissue cells and is then internalized by receptor-mediated endocytosis. A number
      of genetic abnormalities are characterized either by a failure to express
      transcobalamin II or by synthesis of an abnormal protein. These disorders result
      in cellular cobalamin deficiency and megaloblastic anaemia. In this chapter we
      review the structural and functional properties of transcobalamin II, the
      receptor for the transcobalamin-cobalamin complex and the clinical disorders that
      are associated with perturbation of circulating transcobalamin II. In addition,
      we provide emerging data about the molecular genetics of transcobalamin II which
      has emanated from our own and other laboratories.

PMID- 8534960
TI  - Gastric intrinsic factor and its receptor.
AB  - Cbl metabolism has been the subject of many studies since the existence of Cbl
      was suspected in the first decades of the twentieth century. These studies have
      confirmed the high complexity of the assimilation of Cbl by the organism. During
      absorption, Cbl is bound to two glycoproteins, Hc and IF, in a consecutive
      manner. Over the last few years, it has been demonstrated that Cbl bound to Hc in
      the stomach is only transferred to IF after the action of pancreatic trypsin. It
      is also possible that Hc-bound biliary Cbl is transferred to IF in this way and
      that the Cbl in the Cbl-IF complex is absorbed in the terminal ileum, thus
      constituting an enterohepatic cycle. Knowledge concerning the sites of synthesis
      and secretion of IF is becoming more detailed due to the use of
      immunocytochemistry and in situ hybridization techniques. It is now certain that
      in man, IF is not only localized in gastric parietal cells, but also in other
      foregut-derived cells. This observation may explain the multiple physiological
      stimuli involved in mediating IF secretion. Determination of the molecular
      structure of purified Cbl binders can be added to the significant progress made
      due to the application of molecular biology techniques to the field of isolation
      and structural characterization of cDNA encoding Cbl binders, and particularly
      IF. Studies of IF, Hc and TC in different species and those into the properties
      of acceptor fragments have allowed the distinction between the Cbl binding site
      on IF and the IF-Cbl binding site on the IFCR. The absence of experimental models
      cause difficulties in studying transcytosis of Cbl through the enterocyte. There
      are also problems in determining the structure of IFCR as it is difficult to
      obtain a large quantity of a molecule which denatures very quickly. Studies into
      IFCR expression in polarized cancerous cells of intestinal or renal origin,
      including the effects of different pharmacological agents, along with the results
      of immunochemical investigations are beginning to clarify the pathway involved in
      the transport of Cbl through the enterocyte.

PMID- 8534961
TI  - Metabolite assays in cobalamin and folate deficiency.
AB  - Cbl and folate are both necessary for the metabolism of HCYS, whereas only Cbl is
      required for MMA metabolism. During the past decade, analytical methods have been
      developed that are sensitive enough to detect low levels of MMA and HCYS normally
      present in the plasma. These methods are sufficiently precise to be used in the
      clinical laboratory and measurements of the serum levels of the metabolites
      provide sensitive and specific techniques for the identification of Cbl and
      folate deficiencies. These techniques constitute an important addition to the
      battery of diagnostic tests that are available for detecting the vitamin
      deficiencies and for distinguishing each from the other. By virtue of the role of
      Cbl and folate in the metabolic pathways that involve MMA and HCYS, levels of
      both metabolites rise in Cbl deficiency, but only HCYS rises in folate
      deficiency. During the development of Cbl or folate deficiencies, accumulation of
      these metabolites in the plasma signals the existence of a condition of
      biochemical vitamin deficiency of sufficient degree to cause impairment in the
      metabolic pathways which are dependent on these vitamins. Circulating metabolite
      levels appear to accurately reflect the nutritional status of the vitamins and a
      rise in serum metabolite levels is therefore one of the earliest and most
      reliable indicators of developing Cbl and folate deficiencies. Elevations of
      serum metabolites above the reference range not only precede a fall in the serum
      vitamin levels but also show a more consistent correlation with objective
      evidence of vitamin deficiency than do low blood vitamin levels. The advent of
      serum metabolite measurements has also made it possible to identify subtle or
      atypical forms of vitamin deficiency that may be associated with unusual or
      previously undiscovered disease manifestations. Thus, in patients who display
      only neurological manifestations of disease, underlying Cbl deficiency may be
      revealed by the finding of raised serum or urine levels of MMA. Similarly,
      unsuspected folate deficiency may be disclosed by the finding of a raised serum
      HCYS. This may have important implications with respect to disease risk, since
      there is mounting evidence that sub-optimal folate nutritional status may be
      associated with increased risks of vascular disease, neoplasia and birth defects.
      Finally, the measurement of serum levels of MMA, HCYS and other metabolites that
      accumulate in Cbl and folate deficiencies may provide important new insights into
      the mechanism whereby these vitamin deficiencies lead to different patterns and
      manifestations of disease.

PMID- 8534962
TI  - Inherited errors of cobalamin metabolism and their management.
AB  - Cobalamins are essential biological compounds structurally related to haemoglobin
      and the cytochromes. Although the basic cobalamin molecule is only synthesized by
      micro-organisms, all mammalian cells can convert this into the coenzymes
      adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). AdoCbl is the major form
      in cellular tissues, where it is retained in the mitochondria. MeCbl predominates
      in blood plasma and certain other body fluids such as breast milk; in cells MeCbl
      is found in the cytosol. Inherited disorders of cobalamin metabolism are single
      gene defects, transmitted as recessive traits. They affect absorption, transport
      or intracellular metabolism of cobalamin. At least 12 different mutations are
      known, including defects or deficiencies of IF, IF-receptor and TCII, MM-CoA
      mutase and of the various reductases and synthases required for synthesis of
      AdoCbl and MeCbl. These have been designated cblA to cblG. Abnormalities are
      detectable by urine and plasma assays of methylmalonic acid and homocysteine, and
      plasma and erythrocyte analysis of cobalamin coenzymes, which can reveal
      deficiencies of MeCbl or AdoCbl. Fibroblast studies discriminate between closely
      similar defects. In man, AdoCbl is required in only two reactions: the catabolic
      isomerization of MM-CoA to succinyl-CoA and interconversion of alpha- and beta
      leucine. MeCbl is required in the anabolic transmethylation of homocysteine to
      methionine. Intestinal absorption of cobalamin requires the glycoproteins TCI and
      IF from the stomach and IF-cobalamin receptors in the ileum. Cobalamin is
      transported to cells bound to a polypeptide, TCII, is captured by surface
      receptors and absorbed by endocytosis. The complex is then split in the
      lysosomes, cobalamin is released and the coenzymes are synthesized. In plasma, 80
      90% of the cobalamin is bound to TCI, whose function is uncertain. Megaloblastic
      anaemia at birth or in the first few weeks of life is a rare but serious event.
      Myelopathy and developmental delay, with or without seizures may also occur
      without anaemia. If urine and light-protected blood samples are collected and
      sent to an appropriate metabolic unit, an inborn error of cobalamin metabolism,
      including TCII deficiency in which the serum B12 may be normal, can quickly be
      diagnosed. IF deficiency or Imerslund-Grasbeck disease usually presents with
      signs of cobalamin deficiency within the first year of life and can be diagnosed
      by absorption studies. Current treatment involves dietary protein restriction
      and/or parenteral OHCbl and the prognosis is very variable. Since lack of MeCbl
      leads to depressed DNA synthesis affecting rapidly dividing cells in the brain
      and elsewhere, treatment with this coenzyme should be considered at the earliest
      stage in appropriate cases.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8534963
TI  - Congenital errors of folate metabolism.
AB  - Congenital errors of folate metabolism can be related either to defective
      transport of folate through various cells or to defective intracellular
      utilization of folate due to some enzyme deficiencies. Defective transport of
      folate across the intestine and the blood-brain barrier was reported in the
      condition 'Congenital Malabsorption of Folate'. This disease is characterized by
      a severe megaloblastic anaemia of early appearance associated with mental
      retardation. Anaemia is folate-responsive, but neurological symptoms are only
      poorly improved because of the inability to maintain adequate levels of folate in
      the CSF. A familial defect of cellular uptake was described in a family with a
      high frequency of aplastic anaemia or leukaemia. An isolated defect in folate
      transport into CSF was identified in a patient suffering from a cerebellar
      syndrome and pyramidal tract dysfunction. Among enzyme deficiencies, some are
      well documented, others still putative. Methylenetetrahydrofolate reductase
      deficiency is the most common. The main clinical findings are neurological signs
      (mental retardation, seizures, rarely schizophrenic syndromes) or vascular
      disease, without any haematological abnormality. Low levels of folate in serum,
      red blood cells and CSF associated with homocystinuria are constant. Methionine
      synthase deficiency is characterized by a megaloblastic anaemia occurring early
      in life that is more or less folate-responsive and associated with mental
      retardation. Glutamate formiminotransferase-cyclodeaminase deficiency is
      responsible for massive excretion of formiminoglutamic acid but megaloblastic
      anaemia is not constant. The clinical findings are a more or less severe mental
      or physical retardation. Dihydrofolate reductase deficiency was reported in three
      children presenting with a megaloblastic anaemia a few days or weeks after birth,
      which responded to folinic acid. The possible relationship between congenital
      disorders such as neural tube defects or dihydropteridine reductase deficiency
      and disturbances of folate metabolism are discussed. Neurological symptoms
      present in most of these congenital disorders highlight the role of folate in the
      central nervous system.

PMID- 8534964
TI  - Effects of folate deficiency on embryonic development.
AB  - While there is strong evidence that folate deficiency including the use of anti
      folate drugs in early pregnancy is teratogenic and may lead to a range of serious
      abnormalities of the developing fetus including intrauterine death, the
      mechanism(s) for these effects have not yet been delineated. In neural tube
      defects, there is increasing evidence that marginal folate status exacerbates the
      effect of an underlying genetic defect in the mother, the fetus, or both. An
      abnormal relationship between the ingestion of folate and the folate levels in
      red blood cells has been found in women who have given birth to infants with
      neural tube defects. Periconceptional folate supplementation has been shown to
      give effective protection against the development of neural tube defects. The
      mechanism of the prevention is as yet unknown. However, folic acid will not
      prevent all cases of neural tube defect. Moreover, neither determinations of
      periconceptional vitamin profiles (Mooij et al, 1993) nor determinations of
      methylmalonic acid and homocysteine levels will detect all women at risk.
      Anencephaly and spina bifida can be identified prenatally by detection of
      excessive levels of alpha-fetoprotein in amniotic fluid and maternal serum and by
      ultrasonographic scanning (Wilson and Rudd, 1993). Both genetic counselling and
      prenatal diagnosis should be offered to women who are recognized to be at high
      risk. Research into the underlying biology of neural tube defects is of major
      importance. The identification of underlying genetic defects would allow for
      genetic testing and better counselling of families at risk for the occurrence of
      a neural tube defect.

PMID- 8534965
TI  - Malabsorption of food cobalamin.
AB  - Food-cobalamin malabsorption is marked by the inability to release cobalamin from
      food, which therefore cannot be taken up by intrinsic factor for absorption. The
      defect is not detectable by classical clinical tests like the Schilling test
      which are all based on the absorption of free, crystalline cobalamin. Tests of
      food-cobalamin absorption have been devised, the most popular ones using
      cobalamin bound to eggs or to chicken serum. The disparity between the abnormal
      results of these tests and the normal results with the Schilling test defines the
      disorder of food-cobalamin malabsorption. Release of cobalamin from food requires
      acid and pepsin, and most food-cobalamin malabsorptive states can be traced to
      gastric defects. However, other mechanisms may also play a role. The
      malabsorption is limited to food cobalamin and any free cobalamin, presumably
      including recycled biliary cobalamin, will be absorbed normally, which may
      explain its frequently insidious nature. The effect on cobalamin status covers a
      broad spectrum. At one extreme, some individuals, perhaps in the earliest stages,
      have normal cobalamin status, while at the other extreme may be found deficiency
      every bit as severe as in the most florid case of pernicious anaemia. Most often,
      however, the deficiency is mild, frequently marked by only a low serum cobalamin
      level, mild evidence of metabolic insufficiency and, sometimes, minimal clinical
      sequelae. Moreover, in some cases the gastric defect progresses and intrinsic
      factor secretion is affected, thus transforming into classical pernicious
      anaemia; this is not inevitable, however, and probably occurs in only a minority
      of patients. The course of food-cobalamin malabsorption is therefore a varied
      one. Nevertheless, it may be the most common cause of subtle or mild cobalamin
      deficiency and it is also sometimes associated with severe deficiency. Its
      identification and treatment need to be considered more widely in the clinical
      setting.

PMID- 8534966
TI  - Neurological complications of acquired cobalamin deficiency: clinical aspects.
AB  - Neuropsychiatric syndromes occur in about 40% of Cbl-deficient patients and are
      characterized by progressive and variable damage to the spinal cord, peripheral
      nerves and cerebrum. The first abnormality is usually sensory impairment, most
      often presenting as distal and symmetrical paraesthesiae of the lower limbs and
      frequently associated with ataxia. Almost all patients demonstrate loss of
      vibratory sensation, often in association with diminished proprioception and
      cutaneous sensation and a Romberg sign. Corticospinal tract involvement is common
      in more advanced cases, with abnormal reflexes, motor impairment and, ultimately,
      spastic paraparesis. A minority of patients exhibit mental or psychiatric
      disturbances or autonomic signs, but these rarely if ever occur in the absence of
      other neurological changes. Because N2O inactivates Cbl, abuse of the gas may
      lead to typical Cbl neuropathy. Haematological changes are minimal and serum Cbl
      levels and Schilling tests normal in most patients. The severity of neurological
      abnormalities prior to treatment correlates with the duration of symptoms and the
      haemoglobin level. Initial severity, symptom duration and initial haemoglobin
      also correlate with residual neurological damage after Cbl therapy. The inverse
      correlation between severity of anaemia and neurological damage is not
      understood. Diagnosis of Cbl neuropathy can usually be made in the presence of
      the typical neuropsychiatric abnormalities, a low serum Cbl level and evidence of
      megaloblastic haemopoiesis. In some patients serum MMA and HCYS determinations or
      a therapeutic trial may be required. A neurological response usually occurs
      within the first 3 months, although further improvement may occur with time.
      Patients with advanced disease may be left with major residual disability.
      Therefore early diagnosis is critical. Pharmacological doses of folic acid
      reverse the haematological abnormalities of Cbl deficiency. This may allow
      neuropathy to develop or progress and make recognition of deficiency more
      difficult. There is no clear evidence that folic acid therapy precipitates or
      exacerbates Cbl neuropathy. Haematological improvement may occur in a fraction of
      patients receiving small doses of folate, but the data are inadequate to predict
      the danger of low levels of folate supplementation in the general population.

PMID- 8534967
TI  - Cobalamin and folate deficiency in the elderly.
AB  - Elderly persons are more likely to have low values for serum and erythrocyte
      folate, and for serum cobalamin. Many of those with low vitamin levels have
      biochemical abnormalities consistent with true deficiency, including increased
      formiminoglutamic acid excretion, abnormal marrow deoxyuridine suppression, and
      raised serum levels of methylmalonic acid and homocysteine. Therapy with the
      appropriate vitamin reverses the biochemical defect. Despite this, the clinical
      consequences for most elderly persons are remarkably few. True megaloblastic
      anaemia is rare, and the small number of therapeutic trials to date have not
      improved the levels of haemoglobin in the treated subjects, although the mean
      corpuscular volume has decreased significantly. There has been recent concern
      that these low blood vitamin levels might be important causes of nervous system
      damage, but studies specifically of the elderly have not demonstrated overall
      improvements in neurological function following therapy. Vascular damage from
      high blood homocysteine levels secondary to cobalamin or folate deficiency
      remains a potential hazard. Dietary insufficiency, malabsorption of protein-bound
      vitamin B12 secondary to atrophic gastritis, and defective absorption of folyl
      polyglutamates seem the likeliest possible causes. Pernicious anaemia, although a
      common cause of severe megaloblastic anaemia in the elderly, is an infrequent
      cause for the low cobalamin levels in population studies. Although the benefits
      are uncertain, the balance of the evidence suggests that one should treat elderly
      persons with low values of cobalamin or folate. Crystalline vitamin B12 and folic
      acid are absorbed normally and are therefore suitable for replacement therapy,
      provided that pernicious anaemia is excluded.

PMID- 8534968
TI  - Cloning and nucleotide sequence of the inulin fructotransferase (DFA I-producing)
      gene of Arthrobacter globiformis S14-3.
AB  - A gene encoding an inulin fructotransferase (DFA I-producing) [EC 2.4.1.200] from
      Arthrobacter globiformis S14-3 was cloned and the nucleotides sequenced, for the
      first time. The sequence indicated that the native enzyme protein is composed of
      392 amino acid residues. The native enzyme is an extracellar enzyme produced in
      the culture supernatant of A. globiformis S14-3, but the nucleotide sequence of
      the gene lacks a sequence for signal peptide for secretion. The 1.5-kb DNA
      fragment encoding the gene was found to produce the active enzyme in the culture
      supernatant of an E. coli clone, under the control of the lac promoter of pUC119.

PMID- 8534969
TI  - Reddish Escherichia coli cells caused by overproduction of Bacillus
      stearothermophilus uroporphyrinogen III methylase: cloning, sequencing, and
      expression of the gene.
AB  - During shotgun cloning of an amylase gene, we found a transformant of Escherichia
      coli with a reddish color. The transformant produced highly water-soluble red
      pigments the molecular masses of which were less than 3000. The plasmid harbored
      by the transformant contained a DNA fragment derived from a strain of Bacillus
      stearothermophilus. Truncation of the insert DNA showed that an 1.1-kbp Sau 3A
      SalI fragment was responsible for the reddish colony. An open reading frame was
      found in the nucleotide sequence of the 1.1-kbp DNA fragment. The production of
      the red pigment was accompanied by a colorless 28-kDa protein. The sequence of
      the 28-kDa protein was highly homologous to bacterial uroporphyrinogen III
      methylases participating in corrinoid biosynthesis. The 28-kDa protein was found
      to be a thermostable uroporphyrinogen III methylase.

PMID- 8534970
TI  - Formation of trehalose from maltooligosaccharides by a novel enzymatic system.

PMID- 8534971
TI  - A self-defense gene homologous to tetracycline effluxing gene essential for
      antibiotic production in Streptomyces aureofaciens.
AB  - By Northern blot analyses with DNA probes carrying 6-demethylchlortetracycline (6
      DCT) biosynthetic genes from Streptomyces aureofaciens NRRL3203, a highly
      expressed gene (tcrC) was detected in a high titer producing mutant derived from
      the parental strain NRRL3203 by NTG mutagenesis. The analysis of the nucleotide
      sequence of the 2.8-kb BamHI fragment containing tcrC gene showed that the
      predicted tcrC gene product is a protein consisting of 512 amino acids. The
      deduced amino acid sequence had a high level identity with that of the self
      defense gene (tet347) of Streptomyces rimosus, known to mediate oxytetracycline
      efflux. The tcrC gene-inactivated strains generated from strain NRRL3203 by gene
      replacement had a 90% decrease in the level of resistance to tetracycline and the
      antibiotic productivity when compared with the parental strain.

PMID- 8534972
TI  - Enhancement of production of IgM and interferon-beta in human cell lines by poly
      lysine.
AB  - The promotive effects of poly-cations on immunoglobulin production was
      investigated using human-human hybridoma cells. Among poly-cations tested,
      epsilon-poly-L-lysine with hydrochloride (approximately 4 kDa), which has been
      used as an antibacterial food additive, had the greatest activity in enhancing
      IgM production of human-human hybridoma HB4C5 cells without stimulating cell
      proliferation. Immunoglobulin production stimulatory (IPS) activity of epsilon
      poly-lysine was not affected by trypsin digestion. It was stable below 60 degrees
      C but completely inactivated with heating at 100 degrees C for 30 min. epsilon
      Poly-lysine also enhanced interferon-beta (IFN-beta) production of human
      osteosarcoma MG-63 cells, but this stimulatory effect was reduced by the trypsin
      digestion.

PMID- 8534973
TI  - cDNA cloning and characterization of gibberellin-responsive genes in photoblastic
      lettuce seeds.
AB  - Two cDNA clones, cLRG5 and cLRG11, that respond to gibberellin (GA) were isolated
      from seeds of photoblastic lettuce (Lectuca sativa L. cv. Grand Rapids) by
      differential screening. Northern blot analysis indicated that the levels of LRG5
      and LRG11 mRNAs were raised to slightly higher levels 10 h after the start of GA
      treatment and the levels were maintained at least for further 8 h, while those in
      the control seeds gradually decreased. Red light irradiation had effects similar
      to GA treatment. The cLRG5 insert encodes a putative polypeptide of 380 amino
      acids that is highly homologous to alcohol dehydrogenases from several higher
      plants. With regard to the cLRG11 insert, no homologous gene has been reported.

PMID- 8534974
TI  - Cloning and nucleotide sequence of the gene encoding dimethyl sulfoxide reductase
      from Rhodobacter sphaeroides f. sp. denitrificans.
AB  - The gene encoding dimethyl sulfoxide (DMSO) reductase, which contains a
      molybdenum cofactor, of the phototrophic bacterium Rhodobacter sphaeroides f. sp.
      denitrificans was isolated using an oligonucleotide probe, which was synthesized
      based on a internal amino acid sequence of the purified enzyme. The DMSO
      reductase gene coded for 822 amino acids (2466 base pairs, M(r) = 89,206) as a
      precursor form having a signal peptide of 42 amino acids. The deduced amino acid
      sequence had high homology with those of some enzymes containing a molybdenum
      cofactor: trimethyl amine N-oxide reductase (48%), biotin sulfoxide reductase
      (44%), and DMSO reductase (29%) of Escherichia coli.

PMID- 8534975
TI  - Isolation and characterization of a novel endo-beta-galactofuranosidase from
      Bacillus sp.
AB  - A soil bacterium capable of growing on a polysaccharide-containing beta(1-
      >6)galactofuranoside residues derived from the acidic polysaccharide of Fusarium
      sp. as a carbon source has been isolated. From various bacteriological
      characteristics, the organism was identified as a Bacillus sp. The bacterium
      produced beta-galactofuranosidase inductively in the culture media. The most
      effective inducer for the beta-galactofuranosidase production was a
      polysaccharide containing beta(1-->5) or beta(1-->6)-linked galactofuranoside
      residues, but gum arabic, gum guar, gum ghati, arabinogalactam, araban, and
      pectic acid did not induce the enzyme. The enzyme had three different molecular
      weight forms. The low molecular-weight form was purified by a combination of
      Toyopearl HW-55 and DEAE-Toyopearl 650S column chromatographies, and preparative
      polyacrylamide gel electrophoresis. The molecular weight of the enzyme was
      estimated to be 67,000 by SDS-polyacrylamide gel electrophoresis. The enzyme was
      most active at pH 6 and 37 degrees C, and was stable between pH 4 to 8 at 5
      degrees C. The action of the enzyme was inhibited by the addition of Cd2+, Co2+,
      Hg2+, Zn2+, iodoacetic acid, and EDTA. The purified enzyme cleaved beta(1-->5)
      and beta(1-->6)-linked galactofuranosyl chains. Based upon the mode of liberation
      of galactofuranosyl residues from pyridylamino-beta(1-->6)-linked
      galactofuranoside oligomers, the enzyme can be classified as an endo-beta
      galactofuranosidase that randomly hydrolyzes the linkage.

PMID- 8534976
TI  - Inhibition of dextran and mutan synthesis by cycloisomaltooligosaccharides.
AB  - Novel cyclic isomaltooligosaccharides, cyclodextran, strongly inhibited the
      dextransucrase reaction. The inhibition was dependent on the cyclodextran
      concentration and greatly enhanced by the first incubation at 30 degrees for 30
      min. Cyclodextran-heptaose and -octaose were competitive inhibitors for sucrose
      yielding Ki's of 0.25 and 0.64 mM, respectively. Both reducing sugar and dextran
      producing activities of dextransucrase were almost equally inhibited by the
      cyclodextrans. Although gamma-cyclodextrin, palatinose, sucrose-monocaprate, and
      maltitol gave 5-35% inhibition, cyclodextran-heptaose gave 95% inhibition.
      Moreover, water-insoluble glucan (mutan) synthesis by the glucosyltransferase
      from Streptococcus mutans was significantly repressed by the addition of
      cyclodextran.

PMID- 8534977
TI  - Cloning of a lignostilbene-alpha,beta-dioxygenase isozyme gene from Pseudomonas
      paucimobilis TMY1009.
AB  - A genomic DNA library of Pseudomonas paucimobilis TMY1009 was constructed using a
      cosmid vector pWE15. Screening of the library for lignostilbene-alpha,beta
      dioxygenase (LSD) isozyme genes was done with a common probe for the alpha, beta,
      and gamma subunits, which composed LSD isozymes. The positive clones obtained by
      colony hybridization were further confirmed by Southern hybridization. A 4.2-kb
      BamHI-HindIII fragment hybridized with the probe was subcloned into pUC118 to
      yield the plasmid pKHE1700. Escherichia coli MV1184 carrying pKHE1700 produced
      one of the LSD isozymes. The cloned LSD was purified and compared with LSD
      isozymes from P. paucimobilis TMY1009. The behavior on column chromatographies
      through all purification steps accorded with that of LSD-III. Furthermore, the
      mobility on polyacrylamide gel electrophoresis, the elution profile on reversed
      phase HPLC, and the partial amino acid sequence were common to the cloned LSD and
      the native LSD-III. Thus the cloned LSD could be identified as LSD-III. It was
      found that the gene of LSD-III (lsdB) was composed of 489 codons.

PMID- 8534978
TI  - Cloning and nucleotide sequence of the ribonuclease T1 gene (rntA) from
      Aspergillus oryzae and its expression in Saccharomyces cerevisiae and Aspergillus
      oryzae.
AB  - A genomic DNA encoding ribonuclease (RNase) T1 from Aspergillus oryzae was cloned
      using a synthetic oligonucleotide probe. The cloned gene (designated rntA)
      encoded functional RNase T1, since an A. oryzae transformant with multiple copies
      of the rntA gene showed higher RNase T1 activity (over 200 times) than a
      transformant with a vector. A cDNA was cloned by reverse transcription polymerase
      chain reaction (RT-PCR) with primers corresponding to the 5' terminus and 3'
      terminus of the reading frame of the rntA gene. Nucleotide sequencing analysis of
      both DNAs found that RNase T1 had a prepro-sequence consisting of 26 amino acids
      and the rntA gene had only one intron (114 bp) in the region encoding the signal
      sequence. The A. oryzae transformant with cDNA controlled by the amyB promoter
      also showed higher activity (over 300 times), indicating that the cloned cDNA
      encoded functional RNase T1. On the other hand, the Saccharomyces cerevisiae
      transformant with cDNA controlled by the GAL1 promoter could not grow on a medium
      containing galactose. These results suggests that A. oryzae may have a protection
      mechanism from RNase T1.

PMID- 8534979
TI  - Effects of lactoferrin and its peptides on proliferation of rat intestinal
      epithelial cell line, IEC-18, in the presence of epidermal growth factor.
AB  - The cell growth-stimulating activity of lactoferrin (LF) in combination with
      epidermal growth factor (EGF) was evaluated by using a rat intestinal epithelial
      cell line, IEC-18. LF was found to be more effective than EGF for inducing an
      increase in cell numbers when cultured for over 6 days using a medium containing
      0.2% fetal calf serum (FCS), although the 3H-thymidine incorporation-stimulating
      activity of EGF was more potent than that of LF. A synergistic effect of LF and
      EGF was observed in both cell proliferation and DNA synthesis assays. The
      increase in cell numbers when stimulated with LF plus EGF corresponded to about 5
      times that of the control. Iron was not required for manifestation of these
      effects of LF. On the other hand, iron-saturated transferrin (TF) had cell-growth
      stimulating activity, but iron-free TF did not, either in the presence or absence
      of EGF. These results indicate that LF induces cell proliferation by a mechanism
      distinct from that of TF. A pepsin-generated hydrolysate of LF (LFH) had an
      activity similar to that of undigested LF, and a peptide with cell-growth
      stimulating activity from bovine LFH was isolated by monitoring its effects in
      combination with EGF on DNA synthesis in IEC-18 cells. Sequence analysis
      indicated that the peptide has the structure Ala-Glu-Ile-Tyr-Gly-Thr-Lys-Glu-Ser
      Pro-Gln-Thr-His-Tyr-Tyr, corresponding to residues 79-93 of bovine LF.

PMID- 8534980
TI  - Enzymatic formation of plant cerebroside: properties of UDP-glucose: ceramide
      glucosyltransferase in radish seedlings.
AB  - The activity of cerebroside synthase (UDP-glucose: ceramide glucosyltransferase)
      was found in the microsomal fraction of radish hypocotyls, and was studied. One %
      of the radioactivity due to UDP-[3H]glucose added to the membrane fraction was
      incorporated into cerebroside within 60 min. Optimum pH and temperature of the
      activity were pH 7.8 and 30 degrees C, respectively. No metal ions enhanced the
      cerebroside synthase activity, dissimilar to that in animal tissues. The apparent
      Km for UDP-glucose was approximately 200 microM. The same activity was also
      observed in radish roots and cotyledons, but proportions of UDP-[3H]glucose
      incorporation were slightly lower than that in hypocotyls. Exogenous ceramide
      species having trihydroxy sphingoid bases, which were major ceramide components
      of radish cerebrosides, usually stimulated cerebroside formation in microsomal
      fractions from radish seedlings, while any ceramide types having dihydroxy
      sphingoid bases were ineffective on the glucosylation reaction. It was assumed,
      therefore, that cerebroside synthase in radish seedlings would have substrate
      selectivity for ceramide species.

PMID- 8534981
TI  - Prodigiosin 25-C perturbs permeation of acetate in a cultured cell line.
AB  - Prodigiosin 25-C had little effect on DNA, RNA, and protein synthesis, and
      cellular ATP content, but the drug markedly inhibited the incorporation of
      acetate into lipid fractions. Under the same conditions, the incorporation of
      other lipid precursors including glycerol, mevalonate, palmitate, and oleate was
      not affected. A decrease in the incorporation of acetate was not due to the
      inhibition of fatty acid biosynthesis, because prodigiosin 25-C did not affect
      the activity of acetyl-CoA synthetase, acetyl-CoA carboxylase or fatty acid
      synthase in cell-free assay systems prepared from rat liver cytosol. In contrast,
      prodigiosin 25-C strongly inhibited the rapid uptake of acetate into acid-soluble
      fraction in intact cells. The results suggest that prodigiosin 25-C specifically
      perturbs the permeation of acetate through plasma membranes.

PMID- 8534982
TI  - Improvement of hyperlipidemia and proteinuria without noticeable growth
      retardation by feeding a methionine and threonine supplemented low-casein diet to
      nephritic rats.
AB  - We have previously demonstrated that low-casein diets supplemented with cystine
      and threonine reduced hyperlipidemia and proteinuria in nephritic rats without
      noticeable protein malnutrition. In the present study, we examined whether or not
      a low-casein diet supplemented with methionine, sulfur amino acid other than
      cystine, and threonine would ameliorate the symptoms without protein malnutrition
      in rats with nephrotoxic serum nephritis by feeding experimental diets for 10
      days. A methionine-threonine-supplemented 8.5% casein diet (8.5 CMT), when
      compared with a basal 20% casein diet, improved hypoalbuminemia as well as
      hyperlipidemia and proteinuria without noticeable growth retardation and fatty
      liver induction in nephritic rats. Fecal bile acid excretion and microsomal
      cholesterol 7 alpha-hydroxylase activity were enhanced by 8.5CMT feeding. These
      results suggest that amino acid-balanced low protein diet would have a beneficial
      effect on the symptoms of nephritis. They also suggest that the
      hypocholesterolemic action of 8.5CMT may be, at least in part, due to increased
      fecal bile acid excretion accompanied by elevated microsomal cholesterol 7 alpha
      hydroxylase activity.

PMID- 8534983
TI  - Chitosan-derived polymer-surfactants and their micellar properties.
AB  - Chitosan derivatives, sulfated N-acyl-chitosan (S-Cn-chitosan) possessing various
      lengths of alkyl chain, were prepared, and the properties of their aqueous
      solutions were examined. The 1H-NMR spectrum of D2O solutions of S-C12-chitosan
      showed broadening of the proton signals caused by aggregation of the alkyl chain.
      The solubility of a hydrophobic compounds, azobenzene, was small in the aqueous
      solutions of S-Cn-chitosan with shorter alkyl chains, but increased with
      increasing length of the chains above C10, showing that micelles had been formed.
      The ESR spectrum of a spin probe, TEMPO, in an S-C14-chitosan solution showed the
      existence of a hydrophobic region in the solution, but this region did not exist
      in the S-C2-chitosan solution. The rigidity of this region was examined by using
      a spin probe, 16-doxyl-stearic acid. From these results, it was revealed that S
      Cn-chitosan with longer alkyl chains formed a novel type of micelle called a
      "polymer micelle," which was more stable than the ordinary micelles formed from
      low-molecular-weight surfactants.

PMID- 8534984
TI  - Histological study of iron deposits in selenium-deficient rats.
AB  - Previous studies have shown that selenium (Se) deficiency is associated with
      hematological abnormalities, which may result in an increased distribution of
      iron in various tissues. This report describes histological studies of the
      location of excess iron deposits in tissues. Male Wistar rats were fed a Torula
      yeast-based Se-deficient [Se(-)] or Se-adequate [Se(+); containing 0.1 mg Se/kg
      as sodium selenite] diet for 8 or 82 weeks. Excised tissues were embedded in
      either paraffin or epoxy resin. A dramatic increase was observed in iron
      deposition in the liver and kidneys of rats on the Se(-) diet. Prussian blue
      stained sections under the light microscope showed iron deposits in the
      parenchymal cells and Kupffer cells of liver and in the proximal tubules of
      kidneys. The liver and kidneys of Se(-) rats had considerably altered morphology:
      lysosomes were enlarged and contained electron-dense areas. X-Ray microanalysis
      showed that the areas that corresponded to the lysosomes contained iron. No iron
      deposits were observed in sections of kidney and liver from rats fed the Se(+)
      diet. Thus, these studies identified subcellular sites of iron deposition in the
      liver and kidneys of Se(-) rats. These iron deposits may be an important factor
      in the pathogenesis of Se deficiency.

PMID- 8534985
TI  - Synthesis of chiral aspyrone, a multi-functional dihydropyranone antibiotic.

PMID- 8534986
TI  - Macrophage stimulation activity of the polysaccharide fraction from a marine alga
      (Porphyra yezoensis): structure-function relationships and improved solubility.
AB  - The polysaccharide fraction from Porphyra yezoensis (PASF) has already been shown
      to stimulate murine phagocytic functions in vivo and in vitro [Y. Yoshizawa et
      al., Biosci. Biotech. Biochem., 57, 1862-1866 (1993)]. In this study, various
      treatments were applied to PASF to assess its structure-function relationships.
      Desulfation of PASF decreased in vitro macrophage-stimulation activity, while
      further sulfation of PASF did not change the activity. Among 7 fractions obtained
      by anion-exchange chromatography of PASF, stronger activity was found in the
      fractions having a lower or higher sulfate content than in those having a medium
      sulfate content. Digests of PASF with beta-agarase showed higher activity and
      solubility, and lower viscosity, than undigested PASF. These results indicate
      that the sulfate groups in PASF, probably porphyran, contributed to the
      macrophage stimulating activity, although a larger number of sulfate groups did
      not always cause stronger activity.

PMID- 8534987
TI  - Enzymatic synthesis of L-tryptophan by Enterobacter aerogenes tryptophanase
      highly expressed in Escherichia coli, and some properties of the purified enzyme.
AB  - We constructed two plasmids that have a strong tac promoter and a structural gene
      for tryptophanase of Enterobacter aerogenes SM-18 (pKT901EA) or Escherichia coli
      K-12 (pKT951EC). The tryptophanase activity of E. coli JM109 transformed with
      pKT901EA (JM109/pKT901EA) was inducible with isopropyl-beta-D
      thiogalactopyranoside, and 3.6 times higher than that of E. aerogenes SM-18.
      Cells of JM109/pKT901EA induced for tryptophanase synthesized L-tryptophan from
      indole, ammonia, and pyruvate more efficiently than E. aerogenes SM-18. Although
      JM109/pKT951EC expressed a similar level of tryptophanase activity to that of
      JM109/pKT901EA, the synthesis of L-tryptophan by the cells of JM109/pKT951EC did
      not proceed well compared with JM109/pKT901EA. Tryptophanases from E. aerogenes
      and E. coli K-12 were purified, and their properties were investigated. The
      purified E. aerogenes tryptophanase showed higher stability against heat
      inactivation than E. coli tryptophanase.

PMID- 8534988
TI  - Isolation of a new minor protein (Ovofactor-1), which has a cell growth promoting
      activity, from hen's egg white by heparin affinity chromatography.
AB  - A proteinaceous component eluted at the concentration of 0.8-1.0 M NaCl was
      obtained from hen egg white by heparin affinity chromatography. On SDS-PAGE, the
      component was resolved into three bands of 18.5, 16.5, and 16.0 kDa. The
      isoelectric point was estimated to be pH 8.8. This stimulated the DNA synthesis
      and proliferation of the cultured cells from chicken embryos. The amino acid
      composition and N-terminal analyses of the main 18.5 kDa component showed that
      this is a novel minor protein in egg white, and therefore was named "Ovofactor
      1".

PMID- 8534989
TI  - Sterilization of microorganisms by the supercritical carbon dioxide micro-bubble
      method.
AB  - Lactobacillus brevis and Saccharomyces cerevisiae were completely sterilized by
      the supercritical (SC) CO2 micro-bubble method. Gaseous (G) and liquid (LQ) CO2
      were used in a similar manner to compare the sterilizing effect. Among the three
      treatments, the microorganisms were only effectively sterilized by the SC CO2
      treatment at 25 MPa and 35 degrees C.

PMID- 8534990
TI  - Stabilization of the tight junction of the intestinal Caco-2 cell monolayer by
      milk whey proteins.
AB  - The tight junction (TJ) of the human intestinal Caco-2-SF monolayer was shown not
      to have been stably formed. TJ was stabilized by incubating the cell monolayer
      with beta-lactoglobulin (beta-Lg) and bovine serum albumin (BSA). Thus, the Caco
      2-SF cell-culture system will provide a useful model for studying the factors
      which stabilize TJ and for investigating the mechanism of TJ regulation.

PMID- 8534991
TI  - Location of the disulfide bonds of the sweetness-suppressing polypeptide
      gurmarin.
AB  - The sweetness-suppressing polypeptide gurmarin has been isolated from the leaves
      of Gymnema sylvestre and consists of 35 amino acid residues including three
      intramolecular disulfide bonds. The primary structure has already been
      determined. The positions of the disulfide bonds were located, by a combination
      of mass spectrometric analysis and sequencing of cystine-containing peptides
      obtained by thermolysin-catalyzed hydrolysis of gurmarin, to be at Cys3-Cys18,
      Cys10-Cys23, and Cys17-Cys33.

PMID- 8534992
TI  - Sensitive chemiluminescence enzyme immunoassay for vascular endothelial growth
      factor/vascular permeability factor in human serum.
AB  - A sandwich chemiluminescence enzyme immunoassay for measuring the level of
      VEGF/VPF in serum was constructed. The detectability of the assay is very low
      (1.0 pg/ml) and the measurable range of the assay was very wide (1-1000 pg/ml).
      The assay showed that the average level of VEGF/VPF in human sera from healthy
      blood donors was approximately 19 pg/ml.

PMID- 8534993
TI  - Antibacterial substance produced by Streptococcus faecium under anaerobic
      culture.
AB  - A facultative anaerobe isolated from Korean domestic soil produced an
      antibacterial substance under strict anaerobic conditions. Based on the
      morphological and biochemical tests, and cellular fatty acid profiles, the
      anaerobe was identified as Streptococcus faecium. An antimicrobial compound
      produced from the S. faecium was identified as 3,7,12-trihydroxy-24-cholanic acid
      methylester on the basis of its physico-chemical analysis. This substance had
      potent antibacterial activities against a test organism harboring multiple
      antibiotic resistance markers, and a variety of pathogenic bacteria. The isolated
      S. faecium produced lactic acid as well as the antibiotic compound under the
      anaerobic conditions.

PMID- 8534994
TI  - Immunochemical crossreactivity between globulins from buckwheat and indigo seeds.
AB  - Immunochemical relationships between salt-soluble proteins (albumins plus
      globulins) from buckwheat and indigo seeds were shown by immunoblot and
      immunodiffusion analyses using rabbit antisera raised against buckwheat
      globulins. These antigenic crossreactivities were roughly consistent with their
      polypeptide components judged by two-dimensional electrophoresis and SDS-PAGE
      analyses.

PMID- 8534995
TI  - Convenient desktop-scale production of the extracellular domain of the human
      growth hormone receptor by an insect-baculovirus secretion system using a protein
      free culture.
AB  - Expression of a gene encoding the extracellular domain of the human growth
      hormone receptor (hGHR-ED) inserted into the genome of Autographa californica
      nuclear polyhedrosis virus was done using a desktop-scale spinner culture.
      Spodoptera frugiperda 9 (Sf9) cells infected with the recombinant virus secreted
      a protein with hGH-binding activity into the medium. Oxygen supplementation was
      required for high level secretion of the product. The highest cell production
      capability was estimated at more than 15 mg hGHR-ED/liter of culture. A protein
      free medium supported the production similar to that obtained in traditional
      serum-containing media. This spinner culture system is simple to operate, and
      does not require expert knowledge of culture techniques.

PMID- 8534996
TI  - Rotundial, a new natural mosquito repellent from the leaves of Vitex
      rotundifolia.
AB  - A new natural mosquito repellent was isolated from fresh leaves of Vitex
      rotundifolia. Its structure was elucidated by an extensive NMR spectral analysis
      to be a cyclopentene dialdehyde named rotundial. This compound possessed potent
      repelling activity against Aedes aegypti.

PMID- 8534997
TI  - Identification of the positions of disulfide bonds of chitinase from a marine
      bacterium, Alteromonas sp. strain O-7.
AB  - Extracellular chitinase from marine Alteromonas sp. strain O-7 is unique because
      of the activation by four major cations contained in sea water, such as Na+, K+,
      Mg2+, and Ca2+. The positions of S-S bonds of Alteromonas chitinase were
      identified. Alteromonas chitinase was fragmented by TPCK-trypsin and
      Staphylococcus aureus V8 protease. The amino acid and sequence analyses of three
      peptides showed that the positions of disulfide bonds are Cys(94)-Cys(99),
      Cys(174)-Cys(196), and Cys(386)-Cys(395).

PMID- 8534998
TI  - Molecular cloning and nucleotide sequence of purine nucleoside phosphorylase and
      uridine phosphorylase genes from Klebsiella sp.
AB  - Klebsiella sp. LF 1202 was isolated as a bacterium that can assimilate adenosine
      as a sole source of carbon and nitrogen [F. Ling et al., Agric. Biol. Chem., 55,
      573-575 (1991)] from a soil sample. Both the purine nucleoside phosphorylase
      (PNPase) and uridine phosphorylase (UPase) of this bacterium were induced
      simultaneously when the bacterium was cultured in a medium containing adenosine
      or uridine as a sole source of carbon and nitrogen. This induction profile is
      different from that of Escherichia coli. Here we cloned and sequenced the gene
      corresponding to each enzyme. The open reading frame (ORF) of the PNPase gene
      consisted of 717 bp that encoded a polypeptide of 239 amino acids with a
      molecular weight of 26,198. The ORF of the UPase gene consisted of 834 bp that
      encoded a polypeptide of 278 amino acids with a molecular weight of 28,912.

PMID- 8534999
TI  - A structural gene encoding beta-amylase of barley.
AB  - A structural gene encoding the beta-amylase that is abundant in the starchy
      endosperm of ungerminated barley seeds was isolated and characterized. It was
      3825 bp in length. In the sequence of the structural gene, a sequence identical
      to that of the cDNA was found to contain seven exons and six introns.

PMID- 8535000
TI  - Nucleotide sequencing of phenylalanine dehydrogenase gene from Bacillus badius
      IAM 11059.
AB  - The nucleotide sequence of the pdh gene coding for PheDH from Bacillus badius IAM
      11059 was analyzed. The gene consists of an ORF of 1140 nucleotides which
      specifies a protein of 380 codons. The primary structure of PheDH is similar to
      PheDH from B. sphaericus, PheDH from Themoactinomyces intermedius, and leucine
      dehydrogenase from B. stearothemophilus, etc.

PMID- 8535001
TI  - Isolation and characterization of a novel 5-oxoprolinase (without ATP
      hydrolyzing) from Alcaligenes faecalis N-38A.
AB  - A screening test was undertaken to isolate a microorganism that produced 5
      oxoprolinase (without ATP-hydrolyzing). The 5-oxoprolinase (without ATP
      hydrolyzing) activity (decyclization activity toward L-pyroglutamate) was found
      in a cell-free extract of Alcaligenes faecalis N-38A, newly isolated from a soil
      sample. The enzyme was purified as a homogeneous preparation. The molecular
      weight of the enzyme was estimated to be 47,000. The decyclization activity was
      specific for L-pyroglutamate, and independent of ATP and metal ions. The reaction
      was a reversible one, i.e., cyclization reaction of L-glutamate to yield
      pyroglutamate was identified.

PMID- 8535002
TI  - [Project "Standards, Option and Guidelines" (I). National Federation of Centers
      for the Fight Against Cancer].

PMID- 8535003
TI  - [How to develop clinical practice guidelines?].

PMID- 8535004
TI  - [Methodology of the development of diagnostic and therapeutic standards, options
      and recommendations in oncology].

PMID- 8535005
TI  - [Review of the literature, information search and critical reading in the field
      of oncology].

PMID- 8535006
TI  - [Standards, options and recommendations for the multidisciplinary organization of
      oncology].

PMID- 8535007
TI  - [Standards, options and recommendations for the practice of oncologic surgery.
      National Federation of Centers for the Fight against Cancer].

PMID- 8535008
TI  - [Standards, options and recommendations for the practice of external radiotherapy
      and brachytherapy in oncology. National Federation of Centers for the fight
      against Cancer].

PMID- 8535009
TI  - [Standards, options and recommendations for a successful practice in
      chemotherapy. National Federation of Centers for the Fight against Cancer].

PMID- 8535010
TI  - [Standards, options and recommendations for a successful practice in radiographic
      imagery in oncology. National Federation of Centers for the Fight against
      Cancer].

PMID- 8535011
TI  - [Standards, options and recommendations for a successful practice in psycho
      oncology. National Federation of Centers for the fight against cancer].

PMID- 8535012
TI  - [Considerations on the organization of oncologic-genetic consultations (a first
      step towards the publication of clinical practice guidelines)].

PMID- 8535013
TI  - [Impact of recommendations for "good practice" on the quality of care].

PMID- 8535014
TI  - [Comments of the National union of private hospitalization in oncology on the
      project "Standards, options and recommendations"].

PMID- 8535015
TI  - [Good practice and what then? ].

PMID- 8535016
TI  - [Cancer vaccines: scientific bases and clinical developments].
AB  - More than 100 years ago, William Coley published the first report of tumor
      regression induced by immune system activation. Since that time, numerous
      clinical trials of cancer vaccines have been carried out. However, active
      immunotherapy has not yet become an established modality of cancer therapy.
      Recently, striking progress has been accomplished in both the understanding of
      antitumor immune response and the characterization of tumor rejection antigens in
      human species. This progress serves as a basis for the development of new cancer
      vaccines.

PMID- 8535017
TI  - [Bases for intravenous administration of cytosine arabinoside in the treatment of
      adult acute myeloid leukemia].
AB  - Cytosine arabinoside (Ara-C) is one of the most active drugs in the treatment of
      adult acute myeloid leukemia and is widely applied at all phases of therapy. In
      spite of its extensive clinical use, controversies exist about the most
      appropriate way and dose of intravenous administration: continuous or bolus
      infusion and standard-, intermediate- or high-dose. The present review focuses on
      the role and place of each modality of administration of Ara-C and on the
      potential interest on hematopoietic growth factors recently given concomitantly
      to Ara-C therapy. Based on available clinical and experimental data, the
      following conclusions can be drawn: conventional continuous infusion Ara-C-based
      regimens remain the standard therapy regarding first remission induction. The use
      of high-dose Ara-C has been followed by improved results in patients with slow
      initial cytoreduction after a first course of treatment and is an interesting
      approach for consolidation protocols. In relapsed and refractory adult acute
      myeloid leukemia, higher than conventional doses undoubtedly enhance the efficacy
      of Ara-C salvage therapy. Encouraging results emerge from the association of
      hematopoietic growth factors administered concomitantly to Ara-C based regimens,
      which need confirmation in prospective randomized placebo controlled comparative
      trials.

PMID- 8535018
TI  - [Epithelial ovarian cancer: what is the consensus in 1995?].
AB  - We debate about a case report of epithelial ovarian cancer, the acknowledge
      therapeutic formalities and the outlook behaviors, now in progress. Indeed, the
      better definition high risks women of epithelial ovarian cancer, and the proving
      of new therapeutic formalities, will allow the improvement of survival rates.

PMID- 8535019
TI  - [In vitro effects of piracetam on the radiosensitivity of hypoxic cells
      (adaptation of MTT assay to hypoxic conditions)].
AB  - This paper describes the adaptation of the MTT assay to hypoxic conditions in
      order to test the in vitro effect of piracetam on hypoxic cells and particularly
      on the radiosensitivity of hypoxic cells since this drug has shown clinical
      effect on acute and chronic hypoxia. The V79 cell line was selected by reference
      to preliminary hypoxic experiments using clonogenic assay and euoxic experiments
      using clonogenic and MTT assays. Cell growth and survival in our hypoxic
      conditions were assessed using MTT assay with an enclosure and special 48-well
      plates both made of glass. Growth curves on glass versus reference polystyrene
      plates were comparable and confirm the validity of using special glass plates.
      Growth curves on glass plates after 1-hour exposure to nitrogen versus air were
      comparable, so there is no bias effect due to gas composition. Survival curves
      using MTT versus reference clonogenic assay were comparable after radiation
      exposure in eu- and hypoxic conditions, and confirm the validity of our original
      technique for creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1
      hour hypoxic exposure. Piracetam gave no cytotoxic effect up to 10 mM of
      piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus
      hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival
      curves after continuous drug exposure to 10 mM of piracetam gave no significant
      effect on the radiosensitivity of hypoxic V79 cells using MTT or clonogenic
      assay. However, this does not preclude a potential in vivo effect of piracetam on
      the radiosensitivity owing to its action on microcirculation and its rheologic
      properties. The adaptation of the MTT assay to hypoxic irradiation conditions
      yields the easy screening of radiosensitizing drugs: shorter incubation, semi
      automatic method and simultaneous analysis with different serial concentrations
      thanks to the special 48-well glass plates.

PMID- 8535020
TI  - [Changes in methylation of tumor cells: a new in situ quantitative approach on
      interphase nuclei and chromosomes].
AB  - DNA methylation is known to be related to the regulation of gene expression. DNA
      methylation patterns are modified in tumors compared to normal tissue, and in
      some cases, these variations are linked to cancer progression. Molecular biology
      techniques are generally used to evaluate DNA methylation status. We describe
      here a simple and fast immunofluorescent method to quantitate in situ DNA
      methylation using an image analyser and a CCD camera. Quantification of relative
      methylation levels in interphase nuclei and metaphase chromosomes was performed
      on digital images of two types of cells with known methylation levels. The
      results from image cytometry corresponded to those obtained by molecular studies.
      Advantages of this approach are that all the DNA of a cell may be examined rather
      than a limited restriction sequence, and that it may be done on a cell by cell
      basis rather than on a heterogenous population. In addition, with this method,
      changes in methylation patterns during tumor progression could be followed and
      eventually used as a marker for prognosis.

PMID- 8535021
TI  - [Prediction of carboplatin clearance from morphological and biological patient
      characteristics].
AB  - Hematologic toxicity of carboplatin is largely dependent on its pharmacokinetics.
      Its seems likely that therapeutic efficacy is also related to plasma drug
      exposure. Dosage adjustments based on isotopic determination of glomerular
      filtration rate have been proposed but their ambulatory use is not conceivable. A
      population pharmacokinetic study was undertaken to determine a relationship
      between patient characteristics and carboplatin clearance. Plasma carboplatin
      pharmacokinetics were determined as ultrafilterable platinum in 70 patients (23
      to 84 years old) treated with different combination regimens including
      carboplatin at doses ranging from 184 to 950 mg (1-hr i.v. infusion) for various
      tumor types. Data were analysed using Nonlinear Mixed Effects Model (NONMEM). The
      data from 34 patients (46 cycles) were used to obtain the most predictive formula
      for the carboplatin clearance (ml/min): [formula: see text] The obtained formula
      was prospectively evaluated with the data from 36 other patients (43 cycles) and
      compared to other methods available to predict carboplatin clearance.
      Prospectively this formula predicted the clearance with a good precision (median
      absolute percent error of 10% range 0-30%) and minimal bias (median percent
      error: 2% range--25-30%). This method of prediction was as accurate as the one
      which requires the glomerular filtration rate to be measured by 51Cr-EDTA
      injection. This formula should allow to individualize very easily the carboplatin
      dosage in adults by multiplying the calculated carboplatin clearance by the area
      under the curve desired for administration.

PMID- 8535022
TI  - [Depression and cancer. Results of an initial study of 707 patients].
AB  - Within a multifactorial etiology of cancers and a bio-psycho-social approach of
      patients, considering, among the risk factors, those related to personality in a
      preventive view, the authors investigate, by an epidemiologic methodology, for a
      correlation between break-down phenomena and the development of a cancer. The
      study was carried out at the Salah Azaiez Institute in 1992 and included 707
      patients aged from 15 to 82 years, 44% presenting a malignant tumour. For a
      retrospective evaluation of break-down semiology, the study is based on DSM-III
      criteria of break-down diagnostic. Search for a clinic/psychic diagnostic
      relation reveals the difficulty of coexistence between break-down signs and the
      development of a cancer. That difficulty increases in case of an organised break
      down.

PMID- 8535023
TI  - Prosthesis for the treatment of metastatic bone disease of the hip: effects of
      radiotherapy.
AB  - Twenty-eight patients with metastatic involvement of the proximal femur were all
      treated by resection and prosthetic replacement. A large femoral prosthetic
      component was routinely fixed with polymethylmetacrylate bone cement. Local
      radiotherapy was delivered preoperatively in two patients and postoperatively in
      seven patients. Postoperative pain relief according to Habermann et al off
      excellent in 81% and good in 15% of the patients. The functional results
      according to the hip-rating scale of Merle d'Aubigne were rated as excellent in
      19%, very good in 22% and good in 22% of the hips. The prognosis for survival was
      superior in those patients with a preoperative Karnofsky performance status index
      of more than 60 points (p < 0.01) and in those patients without postoperative
      pulmonary complications (p < 0.01). The radiographs of the eighteen patients
      surviving three months or longer showed formation of a new bony envelope around
      the femoral prosthetic component in 11 cases (61%) and bone remodelling of the
      distal femur in 12 cases (67%). When analyzed according to local radiotherapy
      these radiographic changes occurred only if no local radiotherapy had been
      delivered to the femur (p < 0.01).

PMID- 8535024
TI  - [Prognostic factors of hepatocellular carcinoma: a multivariate analysis in 113
      patients].
AB  - The aim of this study was to identify clinical, biological or morphological
      prognostic factors in 113 patients with HCC in terms of survival. All patients
      (100 men, aged 65 [28-85], 95% cirrhosis) were diagnosed between 1982-1990. Mean
      survival time was 21 +/- 3 weeks. Eleven (over 25) variables were isolated by
      univariate analysis. A multivariate survival analysis (Cox regression model)
      disclosed that serum creatinine (p = 0.0002), alkaline phosphatase (p = 0.02) and
      Okuda's stage (p = 0.025) were independent predictors of survival. Comparison of
      survival curves for different values of these prognostic variables allows
      division of patients in three groups of prognostic significance in terms of
      survival (p < 0.05). CONCLUSION: these results facilitate stratification of
      patients with HCC to design and evaluate future controlled trials.

PMID- 8535025
TI  - [Hypercalcemia and squamous cell carcinoma of the upper respiratory-digestive
      tracts. Incidence and prognosis].
AB  - We performed a retrospective analysis on all head and neck cancers with
      hypercalcemia seen between January 1988 and June 1993 at the Centre Oscar
      Lambret, cancer center of northern France. Hypercalcemia, non albumin-corrected,
      higher than 2.60 mmol/l was observed in 173 of 3,394 consecutive patients (5%).
      Median age of patients with hypercalcemia was 53 years and 97% of these patients
      were males. All patients with hypercalcemia had advanced or recurrent and/or
      metastatic squamous cell carcinoma of head and neck (SCCHN); 31 of them were not
      pretreated. There was no significant difference in histology between patients
      with or without hypercalcemia, but hypercalcemia was most commonly associated
      with lesions of the oropharynx (p = 0.00001). The median of calcemia was of 2.83
      mmol/l (2.61-4.70). Gastrointestinal and neurologic symptoms respectively
      occurred in 24% and in 14% of patients and bone metastases in 25% of patients.
      Median survival after the first determination of hypercalcemia was of 7 weeks (0
      128) for the overall group of 173 patients and of 12 weeks (1-128) for those 31
      patients with hypercalcemia at initial diagnosis. Prognosis associated factors
      were: efficacy of antitumour treatment, performance status and hypercalcemia
      superior or not to 3 mmol/l. We concluded that hypercalcemia in head and neck
      cancer is usually a late manifestation associated with advanced, recurrent and/or
      metastatic disease and carries a poor prognosis. The prolongation of survival can
      be obtained in some patients if an effective antitumour treatment is feasible.

PMID- 8535026
TI  - [Use of rhodamine 123 for the detection of multidrug resistance].
AB  - Multidrug resistance (MDR) is characterized by the overexpression of P
      glycoprotein (Pgp), which is responsible for decreasing drug uptake and/or
      increasing drug efflux in resistant cells. Although Pgp has a broad-spectrum
      specificity, this protein seems to react preferentially with amphiphilic and
      cationic molecules. Rhodamine 123 (R123) is widely used as a marker for
      mitochondria in living cells and its uptake is dependent on plasma and
      mitochondrial membrane potential. More recently, cross-resistance to R123 in
      cells resistant to adriamycin has been demonstrated and a correlation between
      expression of Pgp and reduced intracellular accumulation of R123 has been shown.
      The measurement of R123 uptake or efflux allows the characterization of cells
      displaying a MDR phenotype with overexpression of Pgp, even with low levels of
      resistance. Other proteins have now been identified which play a role in
      resistance and in drug transport, including MRP. For this reason we need to
      determine if R123 is transported only by Pgp or if R123 is a substrate for
      transport by other drug resistance proteins as well. We also discuss the
      possibilities of using several techniques based on fluorescence with R123 in
      order to fully characterize cells by measuring both Pgp activity and its
      presence/localization.

PMID- 8535027
TI  - [Breast neoplasms: information in question(s). A survey of patients and
      physicians at a cancer treatment center].
AB  - OBJECTIVE: The aim of this study was to know the wishes of our patients for
      information and to compare them with the point of view of our colleagues in a
      cancer center. METHODS: We gave 100 consecutive new patients with breast cancer a
      questionnaire about their needs. The same questionnaire was given in duplicate to
      all our colleagues in the cancer center (n = 53) asking: 1) their own needs of
      information if they had breast cancer 2) how they thought the patients would
      answer. RESULTS: Seventy-five percent of the patients and 81% of the doctors
      returned the questionnaire (28 were men and 15 women; 81% were involved in the
      management of breast cancer). On one hand, concerning information about the
      disease and about the treatment, there was no difference between the needs
      expressed by patients of doctors (as patients). As expected, the two groups
      wanted to be well informed. On the other hand, there was always a statistically
      significant difference between the needs expressed by patients and the opinion of
      doctors who systematically underestimated them. Concerning information to the
      family, 21% of doctors and only 4% of patients didn't want any information to be
      given to their family. Interestingly, 67% of the patients thought the decision
      had to be taken together with the doctor and 56% of the doctors (as patients)
      wished the decision to be taken by the doctor. CONCLUSION: Patients and
      physicians if they were patients, expressed the same high level need of
      information, but the patients needs seemed underestimated by the majority of
      doctors.

PMID- 8535028
TI  - [Population study of dihydropyrimidine dehydrogenase in cancer patients].
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme of 5-fluorouracil (5
      FU) catabolism. The clinical importance of DPD has recently been demonstrated
      with the identification of severe and/or lethal 5-FU-related toxicity in patients
      with suspected or proven DPD deficiency revealed in lymphocytes. We conducted a
      prospective study on 185 cancer patients in order to evaluate the incidence of
      complete or partial DPD deficiency. The population comprised 152 men (mean age
      62.1) and 33 women (mean age 59.2). Sixty eight were head and neck patients
      treated by a 5-day continuous infusion of 5-FU (starting dose 1 g/m2/day, with
      dose adaptation at mid-cycle) for which DPD activity was measured 2-3 days before
      5-FU administration (94 cycles analyzed). DPD activity was measured by a
      radioenzymatic assay using 14C-5-FU. DPD activity showed a unimodal distribution,
      which globally fits a Gaussian distribution. Mean and median DPD activity were
      0.222 and 0.211 nmol/min/mg prot respectively (range 0.065-0.559). No total DPD
      deficiency was found. Neither liver function nor age influenced DPD activity, but
      DPD activity was on average 15% lower in women than in men (0.194 and 0.228
      nmol/min/mg prot respectively, p = 0.03). In patients treated with 5-FU, the risk
      of developing side effects was not linked to pretreatment DPD activity. 5-FU
      related toxicity was linked to FU systemic exposure. The correlation between DPD
      activity and FU clearance was weak (n = 90, r = 0.31, p = 0.002). As a corollary,
      DPD activity in patients requiring a dose reduction was not significantly
      different from DPD activity in patients who did not require dose modification.
      From the present study it appears that total DPD deficiency is a very rare event.
      Although pre-treatment DPD activity cannot be a useful indicator for improving 5
      FU dose adaptation strategy, the identification of partial DPD deficiency (<
      0.100 nmol/min/mg prot, 3% of the population) could lead to starting the
      treatment with a markedly reduce 5-FU dose.

PMID- 8535029
TI  - [Postoperative lymphoceles and lymphatic fistula in gynecologic and breast
      neoplasms].
AB  - The author reports some review articles about post-operative lymphocele in
      gynecological and breast cancer surgery. Post-operative sonography often shows an
      increased incidence of this complication which is unsuspected with only physical
      examination. Curative treatment of the postoperative lymphocele is performed by
      puncture, drainage or excision if lymphocysts become fibrous. Preventive
      treatment after lymphadenectomy is performed by padding of the axilla after
      breast cancer surgery or visceral non-peritonization after extended lymphadeno
      colpohysterectomies. There is no real solution to prevent lymphocele after
      inguinal lymphadenectomy.

PMID- 8535030
TI  - [Prognostic factors in endometrial cancer: apropos of 206 cases treated at the
      Curie Institute].
AB  - From January 1, 1983 to December 31, 1990 two hundred and six patients with an
      invasive, non metastatic endometrial carcinoma were first treated at Institut
      Curie. Initial tumoral staging (TNM) was as follows: stage Ia: 48%, stage Ib:
      31%, stage II: 15% and stage III-IV: 6%. Total hysterectomy or colpohysterectomy
      was performed in 186 cases, with a bilateral oophorectomy in 180 cases. Bilateral
      limited pelvic lymphadenectomy was performed in 116 cases. Brachytherapy was
      performed in the pre-operative setting in 25 cases, in the post-operative setting
      in 134 cases. Only five patients had brachytherapy alone, because of poor medical
      condition. External irradiation was exclusive in 15 cases and added to surgery
      for 68 patients. Median follow-up is 61 months (8-122 months). Five-year survival
      rate is 77% (71-83%); 5-year specific survival rate is 81% (75-87%). Independent
      prognostic factors for survival in multivariate analysis (Cox regression model)
      are tumoral stage (p < 0.0001), ovarian involvement (p < 0.0001), histologic node
      involvement (p = 0.005) and grade (p = 0.01). For local relapse, independent risk
      factors in the same analysis are ovarian involvement (p = 0.0004), tumoral stage
      (p = 0.01), age (p = 0.02) and histologic involvement of cervix (p = 0.04). For
      distant failure, independent risk factors are histologic node involvement (p =
      0.0001), tumoral stage (p = 0.002) and grade (p = 0.003).

PMID- 8535031
TI  - [Social, economical and educational causes of late diagnosis and treatment of
      cancer in Cameroon].
AB  - The aim of the study was the identification of the social, economical and
      educational causes of late diagnosis and treatment of cancer in Cameroon. The
      interview of 200 consecutive patients with histologically proven cancer was
      performed between November 1988 and November 1990 in the Department of
      Radiotherapy at the University of Yaounde Hospital. The interview followed a pre
      written questionnaire. There were 12% early stages and 88% advanced diseases. The
      median time interval between the first symptom and the first consultation was 10
      months (extremes: 3 weeks-5 years). The median time interval between first
      consultation and diagnosis was two months (extremes: 7 days-7 years). Finally the
      time interval between diagnosis and treatment was one month (extremes: 7 days-3
      months). The major reasons for consultation delay were: cost, inaccessibility of
      health structures, ignorance, fear and attempts of traditional medicine. The
      major causes of diagnosis delay were cost of procedures and misdiagnosis. The
      reasons for late treatment were the cost of treatment and lack of confidence of
      patients on treatment results. It is concluded that advances in cancer treatment
      results in Cameroon require educational efforts, health care reorganization, and
      development of regional and international cooperation.

PMID- 8535032
TI  - [Clinical and evolutive aspects of nasopharyngeal T4 N0 neoplasms].
AB  - Nasopharyngeal carcinoma (NPC) is the primary cancer of the head and neck
      localisations in the Salah Azaiz Institute (Tunisia). From 1970 to 1987, 80
      patients with histologically proven T4 N0 NPC, were treated with exclusive
      radiation (70-75 Gy to the primary lesion and 50-55 Gy to cervical lymph nodes).
      The T4 N0 represents 7% of all NPC and 16% of the T4 treated in our Institute.
      Ninety percent of the patients are over 20 years old with a mean age of 52 years.
      The sex-ratio was 4:1. Extension to the brain was observed in 55% of the cases.
      Local control was 70% at 2 months after the end of irradiation. The actuarial
      survival at 5 years was 47%. Distant metastasis represent 13% (30% of all NPC).
      The main failure of treatment was local recurrence. The T4 N0 is probably a
      particular entity concerning the age, the response to radiotherapy and the low
      rate of distant metastasis.

PMID- 8535034
TI  - Diagnostic placebo--another oxymoron?

PMID- 8535033
TI  - [Randomized placebo trial of myeloprotection with goralatide in patients with
      squamous cell carcinoma of the upper respiratory and digestive tracts or
      esophagus, treated with a carboplatin-fluorouracil combination].
AB  - Eighty-four patients with locally advanced, non metastatic squamous cell
      carcinoma of head and neck or esophagus, were included in a multicentric double
      blind randomized trial, comparing goralatide (12.5 or 62.5 micrograms/kg/day, d1
      d4) to placebo, associated with carboplatin (400 mg/m2, d1) and 5-fluorouracile
      (1 g/m2/d continuous IV over 96 hours). Haematological toxicity was analysed on
      221 cycles of chemotherapy. All but one patient were evaluable because of early
      death without haematological toxicity. No significant difference was observed for
      mean nadir of leukocytes, granulocytes, platelets counts and hemoglobin level.
      Duration of haematological toxicity was no significantly different for the two
      groups of patients. Anemia and lymphopenia were more frequent in the goralatide
      treated patients. Clinical and biological tolerability of goralatide was
      excellent.

PMID- 8535035
TI  - Review: DSM-IV and pain.
AB  - The American Psychiatric Association recently published the fourth edition of its
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Although earlier
      editions included pain-related diagnosis, inherent problems in their construction
      limited their applicability. This article discusses how DSM-IV deals with pain,
      with a specific focus on the new diagnostic category of Pain Disorder.

PMID- 8535036
TI  - Do changes in patient beliefs and coping strategies predict temporomandibular
      disorder treatment outcomes?
AB  - OBJECTIVE: This study examined the applicability of the cognitive-behavioral
      model for temporomandibular disorders (TMD) by determining whether changes in TMD
      patient pain-related beliefs and coping over the course of treatment related to
      improvement in symptoms and disability and whether patients' posttreatment
      beliefs and coping predicted future pain and functioning. PATIENTS/SETTING: We
      studied 139 TMD patients at a health maintenance organization or a university
      dental school who completed a clinical trial comparing usual treatment with or
      without a brief cognitive-behavioral intervention. OUTCOME MEASURES/DESIGN: Pain,
      disability, depression, objective physical impairment, and pain beliefs and
      coping strategies were assessed pretreatment and at 3- and 12-month follow-ups.
      RESULTS: Increased ability to control pain and decreased Disease Conviction and
      Passive Coping scores were associated with improved pain, jaw opening, and
      depression from pretreatment to 3-month follow-up. Patient beliefs and coping at
      3-month follow-up did not contribute much to the prediction of pain or physical
      and psychological functioning at 12-month follow-up after controlling for 3-month
      pain and functioning scores. However, passive coping and low ability to control
      pain at 3 months predicted greater activity interference at 12 months.
      CONCLUSIONS: Pretreatment to 3-month follow-up changes in beliefs and coping are
      associated modestly with TMD patient improvement after conservative dental
      treatment with and without a brief cognitive-behavioral intervention. Research is
      needed to develop interventions that produce greater decreases in disease
      conviction, passive coping, and perceived inability to control pain and to
      determine whether these changes mediate symptom and disability improvement.

PMID- 8535037
TI  - Relationship between social desirability and self-report in chronic pain
      patients.
AB  - OBJECTIVE: To examine the relationship between social desirability and self
      report in data collected from chronic pain patients. SETTING: A multidisciplinary
      pain management center located in a major university medical center. PATIENTS:
      Two hundred persons presenting with chronic pain, including low back, head/neck,
      and extremity pain. MEASURES: Marlowe-Crowne Social Desirability Scale, Beck
      Depression Inventory--Short Form, Spielberger Trait Anxiety Inventory,
      Psychosomatic Symptom Checklist, McGill Pain Questionnaire, Pain Disability
      Index, Quality of Life Scale, Pain Drawing. RESULTS AND CONCLUSIONS: Correlations
      showed that patients with greater social desirability response bias reported less
      depression and anxiety but higher levels of pain severity. When depression
      effects were controlled in a regression analysis, social desirability correlated
      positively with self-reported disability. These results show systematic response
      patterns associated with social desirability, suggesting that social desirability
      response biases should be considered in both research and clinical assessments of
      chronic pain patients.

PMID- 8535038
TI  - Assessment of depression in chronic musculoskeletal pain patients.
AB  - OBJECTIVE: To analyze how the cognitive, affective, and somatic-vegetative
      symptoms of depression included in the modified Zung Self-Rating Depression Scale
      (ZSDS) relate to pain severity. SUBJECTS: Three groups of subjects were compared.
      The "no pain" group (n = 64) reported no musculoskeletal symptoms during the
      preceding year, the "low pain" group (n = 119) had a pain rating of < or = 4, and
      the "high pain" group (n = 137) had a rating of > or = 5 on a numerical pain
      rating scale (0-10). METHODS: Sum scores of the ZSDS and means of separate items
      in the three subgroups were compared. Factor analyses were performed to evaluate
      the structure of the ZSDS, and differences between subgroups on weighted factor
      scores were analyzed. RESULTS: The "high pain" group differed statistically
      significantly from both other groups on the sum score and on most of the items.
      Comparison of weighted factor scores in a three-factor solution revealed that in
      Factor I, "Psychic Energy," the "high pain" group differed from both other
      groups. In Factor II, "Despair," no differences between groups were found, while
      in Factor III, "Sleep problems," statistically significant differences were found
      between all subgroups; more severe pain was associated with more sleep problems,
      fatigue, and restlessness. CONCLUSION: ZSDS items describing symptoms which could
      be a consequence of the pain problem (e.g., sleep problems) are clearly related
      more to pain severity than other indicators of depression--e.g., feelings of
      hopelessness. A diagnosis of depression based on a sum score of an inventory
      which contains somatic-vegetative signs of depression may lead to an
      overestimation of depression in chronic musculoskeletal pain patients. in chronic
      musculoskeletal pain patients.

PMID- 8535039
TI  - Differential consequences of left- and right-sided chronic pain.
AB  - OBJECTIVE: To test the neuropsychological hypothesis that left-sided pain will
      have more adverse consequences than right-sided pain by virtue of activation of
      the "depressogenic" right hemisphere. DESIGN: A retrospective analysis comparing
      data of chronic pain patients with left-sided pain to patients with right-sided
      pain. PATIENTS: All of the right-handed patients (n = 85) presenting with
      unilateral shoulder, arm, and hand pain and suspected of having Thoracic Outlet
      syndrome (TOS) were assessed as potential candidates for surgery at the Toronto
      Western Hospital Pain Investigation Unit over a 5-year period. OUTCOME MEASURES:
      Minnesota Multiphasic Personality Inventory (MMPI), SIP (Sickness Impact
      Profile). RESULTS: Contrary to the intuitive expectation that right-sided pain
      would be more disruptive in right-handed subjects, patients with left-sided pain
      had higher MMPI scores for hysteria and hypochondriasis and also had higher
      scores on the physical dimension of the SIP. CONCLUSION: Differences between the
      groups could not be accounted for by different etiologies because the proportions
      and causes of left- and right-sided pain were comparable. The results are
      consistent with the hypothesis that unilateral stimulation activates the
      contralateral cerebral hemisphere and arouses the emotions associated with that
      hemisphere.

PMID- 8535040
TI  - The utility of comparative local anesthetic blocks versus placebo-controlled
      blocks for the diagnosis of cervical zygapophysial joint pain.
AB  - BACKGROUND: The development of target-specific local anesthetic blocks has
      enabled pain physicians to explore the anatomical source of chronic spinal pain.
      However, such blocks rely on subjective responses and may be subject to the
      placebo effect. Comparative local anesthetic blocks have been advocated as a
      means of identifying true-positive cases and excluding placebo responders. This
      paradigm employs two local anesthetics with different durations of action; only
      patients who obtain reproducible relief and correctly identify the longer-acting
      agent are considered positive. OBJECTIVE: Our objective was to evaluate the
      reliability of comparative blocks of the medial branches of the cervical dorsal
      rami in the diagnosis of cervical zygapophysial joint pain. DESIGN: We compared
      comparative blocks and the criterion-standard of randomized, double-blind,
      placebo-controlled blocks. SETTING: The study was conducted at a tertiary
      referral center. PATIENTS: We studied the first 50 consecutive patients referred
      for assessment of chronic neck pain (> 3 months' duration) after a motor vehicle
      accident, who completed a series of placebo-controlled blocks after an initial
      positive response. Patients were 41 +/- 11 years (mean +/- SD) old with a
      male/female ratio of 1:2. METHODS: Patients underwent three blocks using three
      different agents-lignocaine, bupivacaine, and normal saline--administered on
      separate occasions, in random order and under double-blind conditions. The
      diagnostic decision based on comparative blocks alone was compared with that
      based on placebo-controlled blocks. RESULTS: Comparative blocks were found to
      have a specificity of 88%, but only marginal sensitivity (54%). Although
      comparative blocks result in few false-positive diagnoses, their liability is
      that they result in a high proportion of false-negative diagnoses. Expanding the
      comparative blocks diagnostic criteria to include all patients with reproducible
      relief, irrespective of duration, increases sensitivity to 100% but lowers
      specificity to 65%. CONCLUSIONS: Whether physicians use comparative or placebo
      controlled blocks depends upon the implications of their results. If innocuous
      therapy will be prescribed, comparative blocks might suffice. However, when
      diagnostic certainty is critical, such as in a medicolegal context or when
      surgical intervention is contemplated, placebo-controlled blocks are recommended.

PMID- 8535041
TI  - Caffeine and chronic low back pain.
AB  - OBJECTIVE: Although caffeine apparently plays a role in the modulation of pain
      perception in a variety of acute pain states, little is known about its effects
      on the experience of chronic pain. This exploratory study examined the
      relationship between dietary caffeine consumption and the symptoms reported by
      patients with chronic low back pain. DESIGN AND PATIENTS: A retrospective chart
      review was conducted of 131 patients with chronic low back pain (64 men and 67
      women; mean age = 42.1 years; mean duration of pain = 6.1 years) referred to a
      multidisciplinary pain clinic over a 2-year period. Patients were classified as
      low (less than 100 mg; n = 34), moderate (100-400 mg; n = 68) or high (more than
      400 mg; n = 29) caffeine users based on their self-reports of daily coffee, tea,
      and cola consumption. RESULTS: There were no significant differences among the
      low, medium, and high caffeine consumer groups on any self-report measure of pain
      severity, affective distress, anxiety-related symptoms, or sleeping behavior.
      High caffeine users were more likely to be tobacco smokers than low caffeine
      users (79% and 27%, respectively, p < 0.001). CONCLUSIONS: Our findings indicate
      that dietary caffeine consumption is not related to the global experience of pain
      and disability in patients with chronic low back pain, although high caffeine use
      may be embedded in a context of other unhealthy life-style behaviors.

PMID- 8535042
TI  - Continuous epidural infusion of local anesthetics and shorter duration of acute
      zoster-associated pain.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of continuous
      epidural blockade on acute zoster-associated pain, compared with intermittent
      epidural blocks. DESIGN: The design was a retrospective, nonrandomized study.
      SETTING: The study was conducted at a university hospital in Japan from 1982
      through 1992. PATIENTS: A total of 178 otherwise healthy patients hospitalized
      with moderate or severe herpes zoster lesions. INTERVENTIONS: Group A (n = 66)
      had intermittent epidural blocks using 1% mepivacaine, 4-6 ml, three to six time
      daily; group B (n = 43) were given intermittent epidural blocks and parenteral
      acyclovir (500 mg/day) or vidarabine (600 mg/day) for 5 days; group C (n = 69)
      were administered a continuous epidural 0.5% bupivacaine infusion (0.3-1.0 ml/h)
      for approximately 2 weeks and antiviral agents followed by intermittent blocks.
      MAIN OUTCOME MEASURES: The number of treatment days was used as the outcome
      measure. RESULTS: The length of treatment was significantly shorter in group C
      than in groups A or B. For moderate lesions the means (days) were 36.2 [95%
      confidence interval (CI), 31.4-41.7), 45.6 (95% CI, 34.0-61.4), and 26.8 (95% CI,
      22.3-32.3) for groups A, B, and C, respectively (p < 0.01). For severe lesions
      they were 73.3 (95% CI, 55.1-97.7), 81.7 (95% CI, 59.1-113.0), and 44.9 (95% CI,
      35.2-57.3) for groups A, B, and C, respectively (p < 0.01). CONCLUSIONS:
      Continuous epidural blockade for patients with acute zoster can shorten the
      duration of treatment and may reduce the incidence of postherpetic neuralgia.

PMID- 8535043
TI  - Cues parents use to assess postoperative pain in their children.
AB  - OBJECTIVE: Very little is known about the cues parents use to assess pain in
      their children. This study has described the cues (verbal and nonverbal) parents
      reported using to determine how their children felt following surgery. DESIGN AND
      SUBJECTS: The subjects were 176 parents of children undergoing short-stay or day
      surgery. Using pain diaries, parents were asked to provide written responses to
      the question "Did your child give you any clues on how they were feeling?" for
      the day of surgery and 2 days after their children's surgery. Parents also
      provided ratings of their children's pain five times per day using a visual
      analogue scale. SETTING: The study was conducted at a tertiary care children's
      hospital. RESULTS AND CONCLUSIONS: Parents frequently cited using verbal report
      and appetite as cues to how their children were feeling. A variety of other cue
      types were also reported by parents, including activity level, sleep quality,
      visible/audible discomfort, and physiological observations. Cue types were not
      significantly related to the child's gender, and only one cue type was
      significantly related to the child's age (appetite was used more often for older
      children than younger children). The presence or absence of illness behavior cues
      (e.g., protective behavior, visible/audible discomfort) as well as disruptions to
      normal behavior pattern cues (e.g., sleep, level of activity) was related, in the
      expected direction, to the pain intensity ratings. This study provides insights
      into the cues parents use to assess pain in their children and serves as a
      foundation for future studies on parents' assessment of children's pain.

PMID- 8535044
TI  - Prediction and portrayal of repetitive stress-induced lower limb pain disorders
      among soldiers in basic training using videothermography.
AB  - OBJECTIVE: Thermography has been widely espoused for both detecting and
      portraying pain problems. Development of repetitive stress-induced lower limb
      pain during army basic training is a relatively common occurrence. This study was
      designed to assess the usefulness of thermography for differentiating soldiers
      who developed lower limb pain during training from those who did not. This
      information was intended to be used to determine the usefulness of pretraining
      thermograms taken just as people came into the army in predicting which trainees
      would develop these conditions during training. DESIGN: Videothermographic
      pictures were taken of the lower limbs of 639 newly enlisted soldiers who had
      just arrived at a large U.S. Army base but had not yet begun basic training. The
      amount of symmetry was correlated with the development of lower limb pain. Each
      soldier reporting lower limb pain and "controls" with nonpain problems (usually
      minor colds) received a thermographic evaluation identical to the original
      evaluation when they came for their medical examination. RESULTS: Among prebasic
      trainees, 37% showed 1.0 degrees C of asymmetry somewhere in their lower limbs,
      14% were asymmetrical by between 1.1 degrees and 2.0 degrees C, 5% by 3.0 degrees
      C and 4% by 4.0 degrees C or more. Thus, only 40% of the prebasic trainees were
      within accepted "normal" limits before participating in training. Thirty-nine
      percent of those with asymmetrical thermograms developed lower limb pain compared
      with 28% of those with symmetrical thermograms (significant at p < 0.05). It was
      impossible to predict from any thermographic measurement on the lower limbs which
      soldiers were most likely to develop lower limb pain. This held true even for
      those pretrainees with the greatest asymmetries. Eighty-four percent of trainees
      reporting lower limb pain produced abnormal thermograms regardless of whether or
      not they produced abnormal thermograms prior to training. CONCLUSION: Thermograms
      were of little value for either predicting or portraying repetitive stress
      induced lower limb pain in this population.

PMID- 8535045
TI  - Medical decision-making in a patient with a history of cancer and chronic non
      malignant pain.
AB  - The selection of cancer pain treatment modalities depends on careful assessment
      to establish the pathophysiology of the pain complaint. Treatment may consist of
      a single modality--e.g., pharmacotherapy--or multiple modalities--e.g.,
      pharmacotherapy, anesthetic intervention, and radiotherapy for bone pain. Cancer
      patients may present with pain and multiple concomitant medical problems related
      to their primary neoplastic disease, complications of cancer treatment, or
      unrelated conditions including preexisting pain of nonmalignant origin. We
      present the case of a patient with new onset of pain superimposed on chronic
      nonmalignant pain. This case emphasizes the need for careful assessment and the
      close cooperation required between the pain consultant and the referring oncology
      staff to make optimal treatment decisions in the context of a complex medical
      illness.

PMID- 8535047
TI  - Optimum treatment of rhinitis in the elderly.
AB  - With aging, multiple physiological changes occur in the connective tissue and
      vasculature of the nose which may predispose or contribute to chronic rhinitis.
      Accurate differentiation of allergic from nonallergic causes of rhinitis requires
      skin testing or in vitro measures of specific IgE. Empiric treatment with over
      the-counter first generation antihistamines and oral decongestants frequently
      results in CNS, anticholinergic and cardiovascular adverse effects. While newer
      second generation histamine antagonists do not cause these problems, selected
      drugs in this class may cause electrocardiographic QT prolongation and, in rare
      cases, ventricular arrhythmias. Topical therapies including sodium cromoglycate
      (cromolyn sodium), corticosteroids and ipratropium bromide are all well-tolerated
      with minimal adverse effects. Avoidance of allergens and/or irritants is an
      important adjunct in treating patients with allergic and vasomotor rhinitis. If
      all other therapies fail in patients with confirmed allergic rhinitis,
      immunotherapy can be safely instituted in most older patients.

PMID- 8535046
TI  - Potential of antineoplastons in diseases of old age.

PMID- 8535048
TI  - Osteoarthritis in older patients. Optimum treatment.
AB  - A number of therapeutic options to control pain, maintain function and decrease
      disability are available for older patients with osteoarthritis. The indication
      for pharmacological therapy should be restricted to periods with pain. Great
      attention should be given to nonpharmacological interventions such as education,
      exercise, lifestyle modification and emotional support. If medication is
      necessary, most patients require only pure analgesics such as paracetamol
      (acetaminophen); nonsteroidal anti-inflammatory drugs (NSAIDs) should be used if
      patients do not respond to simpler measures. All medication should be carefully
      monitored considering the frequency of adverse drug reactions in older patients.

PMID- 8535049
TI  - Recent advances in geriatric psychopharmacology.
AB  - Psychopharmacotherapy of the elderly must take into account the effects of age
      related changes in the structure and function of the brain and various organs. In
      general, older people are more sensitive than young people to both the
      therapeutic and toxic effects of psychotropic medications, necessitating lower
      doses and longer dosage intervals. This holds true for the treatment of 5 major
      types of psychiatric illness (depression, bipolar disorder, anxiety, psychotic
      disorders and dementia). The tricyclic antidepressants, although efficacious,
      inexpensive, and backed by 30 years of experience, are less well tolerated by the
      elderly than are newer antidepressants such as the selective serotonin uptake
      inhibitors. Problems with monoamine oxidase (MAO) inhibitors, including
      orthostatic hypotension and restrictions in diet and other medication use, have
      been overcome by the advent of reversible selective inhibitors of MAO-A, but the
      efficacy of these in the elderly has yet to be proven in clinical trials. Lithium
      remains the mainstay for the treatment of bipolar disorder. However, careful
      dosing and monitoring of plasma lithium concentrations are required in the
      elderly due to changes in pharmacokinetics and pharmacodynamics which make older
      patients very sensitive to the toxic effects of this medication. Similarly, age
      related changes in the pharmacokinetics and pharmacodynamics of the
      benzodiazepines, the most frequently prescribed medications for anxiety in the
      elderly, result in recommendations for lower doses and preferential use of those
      agents metabolised by conjugation (e.g. oxazepam). Buspirone, a partial serotonin
      5-HT1A-agonist which is better tolerated than benzodiazepines in the elderly, may
      be used as an alternative. The elderly are extremely sensitive to extrapyramidal
      adverse effects which the typical antipsychotics (neuroleptics) exhibit to
      varying extents. The selection of a suitable agent for the treatment of a
      psychotic disorder should be based upon the adverse effect profile of the drug
      and the specific symptoms and situation of the patient. The newer atypical
      antipsychotics, clozapine and risperidone, have yet to be well-studied in the
      elderly. Dementia, exemplified by Alzheimer's disease, is almost exclusively an
      illness of the elderly. Only one medication, tacrine, has been approved for its
      treatment, based on extensive basic research and positive results of several
      clinical trials. Its long-term benefits have yet to be determined and it has
      several adverse effects, including a tendency to increase liver enzymes to the
      extent that the medication has to be discontinued.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8535050
TI  - Epidemiology of adverse drug events in the nursing home setting.
AB  - There is widespread concern about the level of use, particularly the
      inappropriate use, of drugs among elderly residents of nursing homes. Medication
      consumption by these individuals is among the highest of any patient population;
      residents of nursing homes are prescribed an average of 5 to 8 regularly
      scheduled medications in addition to those drugs prescribed on an as needed
      ('prn') basis. Ideally, drug therapy should result in beneficial effects and
      improved quality of life for patients. However, the development of adverse drug
      events (ADEs) can compromise the expected benefits of pharmacotherapy for the
      individual nursing-home resident and may represent a public health problem of
      considerable magnitude.

PMID- 8535051
TI  - Physiological aspects of aging. Implications for the treatment of cancer.
AB  - The aging of the population has focused attention on the special needs of elderly
      patients. The increasing number of elderly people in the world's population has
      led to a parallel increase in the number of older cancer patients. Bias against
      older patients for screening and treatment of cancer exists, whereby effective
      therapies are withheld in the mistaken belief that these patients cannot tolerate
      them. Physiological changes which occur with aging include decreased
      cardiovascular performance, decreased haematopoietic tissue, a respiratory system
      which has been affected by life-long exposure to infection and toxins, decreasing
      renal function and a compromised nervous system. These changes have implications
      for drug toxicity such as possible increased sensitivity to cardiotoxins and
      increased haematological toxicity from myelosuppressive therapy. With the
      physiological decline in renal function with age, drug dosages must be carefully
      evaluated to avoid chemotherapy toxicity and its sequelae. Older patients may
      have increased sensitivity to oral toxicity, in particular, mucositis. There are
      also issues regarding tolerance of the older patient to radiation therapy. The
      haematopoietic growth factors and new antiemetics now available will allow
      chemotherapy to be administered with greater safety while maintaining quality of
      life. Overall, the healthy elderly are appropriate candidates for standard and
      experimental antineoplastic therapy. Careful assessment of end-organ function
      needs to be performed before a decision regarding the proper treatment regimen
      can be made. Clinical trials have rarely included the elderly, making data
      scarce. More research is needed in this age group.

PMID- 8535053
TI  - Switching drug availability from prescription only to over-the-counter status.
      Are elderly patients at increased risk?

PMID- 8535052
TI  - Captopril. A review of its pharmacology and therapeutic efficacy after myocardial
      infarction and in ischaemic heart disease.
AB  - Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used
      extensively in the treatment of patients with hypertension and congestive heart
      failure. In recent years, animal and human studies have demonstrated that
      captopril attenuates left ventricular remodelling (structural changes and
      enlargement) which occurs after myocardial infarction, and can lead to left
      ventricular dysfunction and increased risk of death. Subsequently, large clinical
      trials have shown reduced mortality and morbidity in patients receiving captopril
      or other ACE inhibitors (in addition to standard therapy) after acute myocardial
      infarction. Results of the 4th International Study of Infarct Survival (ISIS-4),
      a factorial trial which randomised more than 58,000 patients, indicate that
      captopril, initiated within 24 hours of myocardial infarction and titrated to 50
      mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks
      after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This
      corresponds to an absolute benefit of 5 lives saved per 1000 patients treated
      with captopril over this period. Furthermore, the survival advantage appeared to
      be maintained at 1 year post-infarction. Although both high- and low-risk
      patients were included in the ISIS-4 trial, the greatest survival benefit of
      captopril occurred in patients at greater risk of mortality, such as those with
      signs of heart failure or previous infarction. A significant relative reduction
      in overall mortality of 19% was seen in patients with left ventricular
      dysfunction (but not overt heart failure or ongoing ischaemia) after acute
      myocardial infarction treated with captopril in the Survival and Ventricular
      Enlargement (SAVE) study. Captopril was started within 3 to 16 days after
      myocardial infarction and titrated to 50 mg 3 times daily for a mean duration of
      42 months. In this high-risk group of patients, approximately 40 to 50 lives were
      saved per 1000 patients treated with captopril over this period. This was similar
      to survival benefits demonstrated with other ACE inhibitors following acute
      myocardial infarction in high-risk patients in other large randomised trials.
      Cost-effectiveness analyses using data from the SAVE trial indicate that
      captopril compares favourably with other interventions used for survivors of
      myocardial infarction. In general, captopril was well tolerated by patients in
      SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to
      standard therapy after acute myocardial infarction, early or late administration
      of captopril improves survival and reduces cardiovascular morbidity, particularly
      in selected high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8535054
TI  - The role of the immune system in anti-tumour responses. Potential for drug
      therapy.
AB  - In the last 5 years significant progress has been made in our understanding of
      the molecular nature of anti-tumour T cell-mediated responses. This review
      describes the involvement of the cellular immune system in the recognition and
      destruction of cancer cells. Four aspects are discussed: (i) the generalized
      immune activation induced by the systemic administration of cytokines, in
      particular, interleukin-2; (ii) the specific T cell-mediated reactions against
      tumour cells through the recognition of tumour-associated molecules, 1) and
      tyrosinase proteins described in melanomas, and minor histocompatibility antigens
      in the setting of allogenic bone marrow transplantation for leukaemia; (iii) the
      potentially significant but still hypothetical immune-mediated recognition of
      molecules either tumour-associated or transformation-related (including altered
      oncogenic proteins); and (iv) the role of co-stimulatory molecules in the
      induction of tumour-specific immunity. The current and future therapeutic
      applications in cancer treatment and potential limitations in this approach are
      discussed.

PMID- 8535056
TI  - Drug poisoning in older patients. Preventative and management strategies.
AB  - Children under 6 years of age are involved in the majority of poisonings.
      However, the elderly are more likely to require hospitalisation and to die from
      poisonings compared with younger individuals. Drugs play an important role in the
      poisoning exposures of older patients. Analgesics, cardiovascular medications,
      theophylline preparations and antidepressants and other psychotropic medications
      are most commonly implicated in drug poisoning fatalities in elderly Americans.
      Careful review of information which characterises drug poisonings in the elderly
      is essential to the development of effective preventative strategies. Most poison
      centre calls for elderly patients involve accidental exposures. The ingestion of
      extra doses of medications because of forgetfulness, mistaken identity of
      medications, incorrect route of administration, and improper storage of
      medications are among the the primary reasons for unintentional drug poisonings
      in older patients. A model for injury control composed of 3 phases can be applied
      to poison exposures in the elderly: activities in the pre-event phase focus on
      prevention; it should occur; the post-event phase is directed at appropriate
      management to reduce the consequence of injury from poison exposure once it
      occurs. The general management of drug poisonings is similar in older and younger
      patients. However, management in the elderly is complicated by difficulties in
      the diagnosis of drug poisoning, pharmacokinetic and pharmacodynamic changes
      associated with aging, increased incidence of chronic illness, and increased
      medication with the potential for clinically significant drug interactions.
      Aggressive initial treatment is imperative because the elderly are generally more
      susceptible to the toxic effects of drugs.

PMID- 8535055
TI  - Age-related changes in vascular smooth muscle and endothelium.
AB  - Aging is associated with structural and functional changes in the blood vessel
      wall. In vascular smooth muscle, the effects of aging on the response mediated by
      beta-adrenoceptors have been most intensively studied. beta-adrenoceptor-mediated
      relaxation decreases in most arteries, but not veins, with increasing age. In
      contrast, studies on contractile responses to alpha-adrenergic drugs are
      conflicting. The response to alpha-adrenoceptor agonists appears to be unchanged
      for decreased by aging. The endothelium takes part in the local regulation of
      vascular tone as a source of several vasoactive factors. Basal release of
      endothelium-derived nitric oxide decreases with age in vitro studies. Aging is
      also associated with reduced endothelium-dependent relaxations in response to
      vasoactive substances such as acetylcholine, histamine or adenosine. The
      impairment of the relaxation is, in most cases, achieved by a decreased release
      and/or decreased production of endothelium-derived relaxing factors (endothelium
      derived nitric oxide, hyperpolarising factor and prostacyclin). An increased
      release of endothelium-derived, cyclo-oxygenase-dependent contracting factor is
      also responsible for reduced relaxation in some tissues. On the other hand, the
      release of endothelin-1 from the endothelium increases with age, while the
      response to the peptide decreases under the same conditions, especially in small
      resistance arteries. The alterations of vascular smooth muscle and endothelial
      cells occurring with age may have important clinical implications for the
      pathogenesis of cardiovascular disease.

PMID- 8535057
TI  - Epidemiology and treatment of post-stroke depression.
AB  - Depression is a common and serious complication after stroke. According to
      epidemiological studies, at least 30% of stroke patients experience depression,
      both early and late after stroke. However, in clinical practice only a minority
      of the patients are diagnosed and even fewer are treated. There are several
      studies confirming the magnitude of the problem but the main conclusion which can
      be drawn from the few treatment studies published is that tricyclic
      antidepressants cannot be recommended for the treatment of post-stroke
      depression, mainly because of the high frequency of contraindications and adverse
      effects. Until now there has only been 1 double-blind, placebo-controlled
      treatment study from which some general conclusions can be drawn. The study
      evaluated a selective serotonin reuptake inhibitor (citalopram) and concluded
      that the drug was well tolerated and effective for the treatment of post-stroke
      depression. However, when treatment was initiated very early, both the treatment
      group and the placebo group improved equally during the first 7 weeks after
      stroke. This finding could indicate diagnosis difficulties during the first few
      weeks after stroke. A recent study, although small, comparing the combination of
      drugs with either noradrenergic (desipramine plus mianserin) or noradrenergic and
      serotonergic effects (imipramine plus mianserin) for post-stroke depression,
      indicated that drugs with the dual effect may be more effective. Many more double
      blind placebo-controlled treatment studies and studies comparing the efficacy and
      adverse effects of various antidepressants in patients with post-stroke
      depression need to be conducted. According to 3 small studies, electroconvulsive
      therapy (ECT) seems to be quite well tolerated and therefore ECT may also be
      considered in the treatment of post-stroke depression. Future studies should also
      address the long term efficacy of treatment for post-stroke depression.

PMID- 8535058
TI  - Sinusitis in the aged. Optimal management strategies.
AB  - Sinusitis is a common medical condition in the elderly; however, the clinical
      presentation is often subtle and the condition may not be readily diagnosed. The
      most important clinical clue to the diagnosis of acute sinusitis is the
      continuation of symptoms after a typical cold has subsided. In chronic sinusitis
      there is often a distinct lack of symptoms, although most patients will have
      nasal obstruction and purulent post-nasal drip. On physical examination, the
      patient with sinusitis will have thick, purulent, green or deep yellow secretions
      in the nasal passages. The use of radiographic imaging, such as sinus
      roentgenograms or CT scans, will help confirm the diagnosis. The goal of
      treatment of sinusitis is eradication of infection with clearance of the infected
      material from the sinuses. While the use of an appropriate antibiotic is
      necessary, the use of ancillary therapy is also of utmost importance. Steam and
      nasal saline, decongestants, topical corticosteroids and mucoevacuants are given
      in an attempt to reduce nasal obstruction, increase sinus ostia size, promote
      improved mucociliary function, decrease mucosal inflammation and thin secretions.
      In selected patients who fail to respond to aggressive medical therapy,
      functional endoscopic surgery can often provide relief. In patients with poorly
      controlled asthma, treatment of underlying sinusitis has been shown to
      dramatically improve the asthmatic state.

PMID- 8535059
TI  - Topical capsaicin. A review of its pharmacological properties and therapeutic
      potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis.
AB  - Capsaicin, the active principle of hot chili pepper, is thought to selectively
      stimulate unmyelinated C fibre afferent neurons and cause the release of
      substance P. Prolonged application of capsaicin reversibly depletes stores of
      substance P, and possibly other neurotransmitters, from sensory nerve endings.
      This reduces or abolishes the transmission of painful stimuli from the peripheral
      nerve fibres to the higher centres. In clinical studies of patients with post
      hepatic neuralgia, diabetic neuropathy or osteoarthritis, adjunctive therapy with
      topical capsaicin achieved better relief than its vehicle in most studies. In a
      single trial, topical capsaicin in demonstrated similar efficacy to oral
      amitriptyline in patients with diabetic neuropathy. Topical capsaicin is not
      associated with any severe systemic adverse effects. However, stinging and
      burning, particularly during the first week of therapy, is reported by many
      patients. Topical capsaicin merits consideration as adjuvant therapy in
      conditions such as post-herpetic neuralgia, diabetic neuropathy and
      osteoarthritis, where the pain can be chronic and difficult to treat.

PMID- 8535060
TI  - Mapping the diabetes polygene Idd3 on mouse chromosome 3 by use of novel congenic
      strains.
AB  - Development of novel congenic mouse strains has allowed us to better define the
      location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3. Congenic strains
      were identified by use of published and newly developed microsatellite markers,
      their genomes fingerprinted by a rapid, fluorescence-based approach, and their
      susceptibility to type 1 diabetes evaluated. The maximum interval containing Idd3
      is now approximately 4 cM.

PMID- 8535061
TI  - A family of rapidly evolving genes from the sex reversal critical region in Xp21.
AB  - Patients with an intact SRY gene and duplications of portions of Xp21 develop as
      phenotypic females. We have recently mapped this sex reversal locus, DSS, to a
      160-kb region of Xp21 that includes the adrenal hypoplasia congenita locus. To
      clone the gene(s) underlying DSS and AHC, we isolated expressed sequences from
      the region. Here we describe the characterization of two related genes. DAM10 and
      DAM6, expressed in adult testis and lung tumors. The predicted DAM10 and DAM6
      proteins are 66% identical and are both highly similar to the MAGE family of
      tumor-associated antigens and to mouse necdin. Genes belonging to the MAGE
      superfamily, DAMs, MAGEs, and necdin, are likely to have originated from a common
      ancestor and to be subject to an unusually rapid evolution. The tumor-restricted
      expression of DAM proteins and their structural similarity to MAGE genes suggest
      that DAM peptides may be targets for active immunotherapy in lung cancer
      patients.

PMID- 8535062
TI  - Mapping of the Hmg1 gene and of seven related sequences in the mouse.
AB  - The High Mobility Group 1 protein (HMG1) is an abundant and highly conserved
      chromosomal protein. Mouse HMG1 is encoded by the Hmg1 gene, containing four
      introns, but the murine genome contains many related sequences that are mostly
      retrotransposed pseudogenes. By using an interspecific cross, we have mapped the
      functional Hmg1 gene on mouse Chromosome (Chr) 5 and seven Hmg1-related sequences
      on Chrs 6, 8, 17, 18, and X.

PMID- 8535063
TI  - Mouse H2 congenic intervals: analysis and use for mapping.
AB  - In this study we exploit the unique genetic resource of inbred mouse major
      histocompatibility complex (H2) congenic and recombinant strains to construct a
      high-resolution map of microsatellite loci in and around the H2 region, as well
      as an independent genetic map of other loci on mouse Chromosome (Chr) 17.
      Microsatellite loci were analyzed in 11 C57BL/10 (B10) strains to determine the
      size of the congenic interval in each. The length of the congenic interval found
      in each strain varied widely. Interestingly, the intervals were generally smaller
      than statistical expectations. However, the observed congenic intervals were
      still sufficiently long that these strains and probably wild-derived H2 congenics
      are an important source of genetic variability. The staggered ends of the various
      congenic intervals and the recombinants were used to construct the map. This map
      will be useful for physical cloning and to help localize novel genes. As evidence
      of the mapping application of congenic strains, locational information was
      derived about Trp53-ps and Stl.

PMID- 8535064
TI  - Mouse chromosome-specific painting probes generated from microdissected
      chromosomes.
AB  - Using degenerate primer amplification of chromosomes microdissected from banded
      cytogenetic preparations, we constructed both whole chromosome painting probes
      for mouse Chromosomes (Chrs) 1, 2, 3, and 11 and a centromere probe that strongly
      paints most mouse centromeres. We also amplified a Robertsonian translocation
      chromosome microdissected from unstained preparations to construct a painting
      probe for Chrs 9 and 19. The chromosome probes uniformly painted the respective
      chromosomes of origin. We demonstrated the utility of the Chr 11 probe in
      aberration analysis by staining mutants that we had previously identified as
      containing a Chr 11 translocation, and in some mutant cell lines we observed
      chromosome rearrangements not previously detected in stained cytogenetic
      preparations. The technology of microdissection and amplification applies to all
      mouse chromosomes or to specific subchromosomal regions and will be useful in
      mouse genetics, in aberration analysis, and for chromosome identification.

PMID- 8535065
TI  - Use of simple sequence length polymorphisms for genetic characterization of rat
      inbred strains.
AB  - Genetic monitoring is an essential component of colony management and for the rat
      has been accomplished primarily by using immunological and biochemical markers.
      Here, we report that simple sequence length polymorphisms (SSLPs) are a faster
      and more economical way of monitoring inbred strains of rats. We characterized 61
      inbred strains of rats, using primer pairs for 37 SSLPs. Each of these loci
      appeared to be highly polymorphic, with the number of alleles per locus ranging
      between 3 and 14 and, as a result, all the 61 inbred strains tested in this study
      could be provided with a unique strain profile. These strain profiles are also
      used for estimating the degree of similarity between strains. This information
      may provide the rationale in selecting strains for genetic crosses or for other
      specific purposes.

PMID- 8535066
TI  - Characterization and mapping of a highly conserved processed pseudogene and an
      intron-carrying gene of the heat shock cognate protein 70 (Hsc70) gene family in
      the rat.
AB  - A processed pseudogene of the rat Hsc70 gene, Hsc70-ps1, is described, which
      still presents the open reading frame of the original gene. The pseudogene does
      not appear to be expressed. It maps to rat Chromosome (Chr) 2. The intron
      carrying Hsc70 gene localizes to Chr 8. Hsc70-specific probes detect a large
      number of more than 20 cross-hybridizing fragments, which show only limited
      length polymorphism among various inbred rat strains.

PMID- 8535067
TI  - Mapping of the SLA complex class III region by pulsed field gel electrophoresis.
AB  - The fine order of genes in the class III region of the swine major
      histocompatibility complex (MHC), the SLA complex, was examined by pulsed field
      gel electrophoresis (PFGE) and Southern blot analysis. Four genes, C2, HSP70, TNF
      alpha, and CYP21, were analyzed. The CYP21, C2, and HSP70 genes were all located
      within a 200-kb NotI fragment. The C2, HSP70, and TNF alpha genes cohybridized to
      a 420-kb SalI fragment. The TNF alpha gene is linked to the class I region by a
      390-kb NotI fragment. Combined with a previous study from our lab, the order of
      genes in the SLA complex is class II-class III [(CYP21/C4)-(Bf/C2/HSP70)-TNF
      alpha]-class I. The size of the class III region from CYP21 to TNF alpha is
      estimated to be 500 kb. This size and the order of the genes in the swine class
      III region are similar to those of human, mouse, goat, and rabbit, which confirms
      the high conservation of class III gene organization across species.

PMID- 8535068
TI  - Identification and characterization of a novel conserved DNA repeat.
AB  - Homozygous In(10)17Rk mice contain a paracentric inversion within Chromosome
      (Chr) 10 and exhibit a pygmy phenotype, suggesting that the distal inversion
      breakpoint is within the pygmy (pg) locus. In order to obtain the pygmy gene by
      positional cloning procedures, In(10)17Rk DNA was subjected to RFLP analysis with
      single-copy probes derived from the wild-type pygmy locus. This analysis
      identified a DNA polymorphism in the DBA/2J mouse strain on which the In(10)17Rk
      mutation was originally induced. A detailed characterization of this polymorphism
      revealed the presence of a novel, tandemly repeated DNA element. Copy number
      estimation experiments indicate that there are approximately 100,000 copies of
      this element in the haploid DBA/2J genome. PCR typing studies revealed the
      presence of the repeat at the pygmy locus of 6 of the 18 Mus domesticus strains
      analyzed. The absence of the repeat from the pygmy locus of 12 strains of the M.
      domesticus species and from the M. caroli, M. spretus, M. castaneus, and M.
      molossinus species suggests that the repeat could serve as a strain-specific
      hybridization probe in genetic mapping studies. Finally, the novel tandem DNA
      repeat is conserved in both rat and human genomes as indicated by Southern
      hybridization experiments.

PMID- 8535069
TI  - Use of interspersed repetitive sequences-PCR products for cDNA selection.
AB  - In order to increase the efficiency of cDNA selection approaches, we describe the
      use of interspersed repetitive sequences-PCR (IRS-PCR) products to isolate genes
      from large-insert genomic clones. IRS-PCR is conducted on total yeast DNA
      containing a YAC of interest so that there is no need to purify the starting
      genomic clone. This enables the production of large amounts of genomic substrate
      for cDNA selection and allows the use of unstable YAC clones. Moreover, the
      hybridization of the IRS-PCR product to the cDNA clones after selection
      introduces a positive selection step. We tested these PCR products from YACs for
      the presence of exons, using cDNAs originating from seven different genes. In
      each case, at least one exon was present in the IRS-PCR product. We have applied
      this strategy to four YAC clones originating from the human X Chromosome (Chr).
      All the selected cDNAs, strongly positive with the IRS-PCR product, did indeed
      originate from a gene in the region covered by the YAC. In all cases, the
      previously known genes contained in the genomic clones have been isolated. In
      addition, we have isolated human genes that have already been described but not
      assigned to any chromosomal region.

PMID- 8535070
TI  - A linkage map with microsatellites isolated from swine flow-sorted chromosome 11.
AB  - We have developed a simple and efficient method to construct partial libraries of
      swine Chromosome (Chr) 11, starting with only 300 flow-sorted copies. DNA is
      amplified by PARM-PCR with primer containing at the 5'-end the sequence AGCU-.
      After amplification, digestion of PCR products with uracil DNA glycosylase
      generates cohesive ends corresponding to the SstI site. The amplified fragments
      can then be ligated in vector linearized with the SstI enzyme. Using five
      different primers, we PARM-PCR amplified and cloned swine Chr 11 DNA. These
      chromosome-specific libraries have been used to develop 14 different (TG)n
      microsatellites. Ten of these markers were assigned to Chr 11 by PCR analysis of
      a panel of Pig-Rodent somatic hybrids and by linkage analysis of the 171
      individuals of the PiGMaP reference families. A complete linkage map of 147 cM of
      this chromosome was then realized by integrating existing markers.

PMID- 8535071
TI  - Chromosomal localization and molecular characterization of 53 cosmid-derived
      bovine microsatellites.
AB  - Gene mapping in cattle has progressed rapidly in recent years largely owing to
      the introduction of powerful genetic markers, such as the microsatellites, and
      through advances in physical mapping techniques such as synteny mapping and
      fluorescence in situ hybridization (FISH). Microsatellite markers are often not
      physically mapped because they are generally isolated from small insert plasmid
      libraries, which makes their chromosomal localization inefficient. In this report
      we describe the FISH mapping of a large group of cosmid-derived bovine
      microsatellite markers, as our contribution to the European mapping initiative,
      BovMap. One objective of BovMap is to develop a set of anchored loci for the
      cattle genome map. Two cosmid libraries were screened with probes corresponding
      to the (AC)n microsatellite motif. Positive clones were mapped by FISH, and then
      a subset was further analyzed by sequencing the region flanking the
      microsatellite repeat. In total, 58 clones were hybridized with chromosomes and
      identified loci on 22 of the 31 different bovine chromosomes. Three clones
      contained satellite DNA. Two or more markers were placed on 12 chromosomes.
      Sequencing of the microsatellites and flanking regions was performed directly
      from 43 cosmids, as previously reported (Ferretti et al. Anim. Genet. 25, 209
      214, 1994). Primers were developed for 39 markers and used to describe the
      polymorphism associated with the corresponding loci.

PMID- 8535072
TI  - The role of melanocyte-stimulating hormone (MSH) receptor in bovine coat color
      determination.
AB  - The melanocyte-stimulating hormone (MSH) receptor has a major function in the
      regulation of black (eumelanin) versus red (phaeomelanin) pigment synthesis
      within melanocytes. We report three alleles of the MSH-receptor gene found in
      cattle. A point mutation in the dominant allele ED gives black coat color,
      whereas a frameshift mutation, producing a prematurely terminated receptor, in
      homozygous e/e animals, produces red coat color. The wild-type allele E+ produces
      a variety of colors, reflecting the possibilities for regulating the normal
      receptor. Microsatellite analysis, RFLP studies, and coat color information were
      used to localize the MSH-receptor to bovine Chromosome (Chr) 18.

PMID- 8535073
TI  - A putative human equivalent of the murine Xlr (X-linked, lymphocyte-regulated)
      protein.
AB  - The murine Xlr (X-linked, lymphocyte-regulated) gene family was originally
      identified by subtractive cDNA hybridization and cloning. It was found to encode
      two 30-kDa nuclear proteins expressed in lymphoid cells and in primary
      spermatocytes in a developmentally regulated manner. Our data show that, in
      contrast to most X-linked genes, the Xlr family is not conserved at the DNA level
      between mouse and human. However, using anti-Xlr antibodies, an Xlr
      immunoreactive nuclear protein of M(r) 30,000 was characterized in human RAJI B
      lymphoblastoid cells by flow cytofluorimetry, by immunoblotting, and by
      immunocytolabeling. An Xlr-like molecule was also found to be expressed in human
      activated lymphocytes and in human primary spermatocytes, with a stage
      specificity similar to that known in the mouse. In contrast, no Xlr
      immunoreactive protein was detected in a series of human tissues including brain,
      skeletal muscle, colon, liver, and kidney, revealing a tissue-specific expression
      pattern similar to that of murine Xlr. These findings most likely identify a
      human equivalent of Xlr. The Xlr genes belong to a small category of X-linked
      genes, including STS, MIC2, CSF2RA, and KAL, that diverge at the DNA level in
      human and in mice. Characterization of the human XLR gene(s) should now be
      feasible with anti-Xlr antibodies and an expression cloning system. It should
      provide new insights into the evolution of mammalian X Chromosome (Chr).

PMID- 8535074
TI  - Molecular genetic analysis of the human sorbitol dehydrogenase gene.
AB  - The polyol pathway comprises the enzymes aldose reductase and sorbitol
      dehydrogenase, which convert glucose to sorbitol and sorbitol to fructose,
      respectively, particularly in hyperglycemic states. The accumulation and toxicity
      of sorbitol in specific tissues has been implicated in the development of
      microvascular problems in some diabetic patients. Inappropriate sorbitol
      accumulation in some patients may be the result of polymorphic variation in the
      human sorbitol dehydrogenase gene, causing reduced expression levels or enzymatic
      activity. We now describe the structure and expression profile of the human
      sorbitol dehydrogenase gene and identify a range of polymorphic variants that may
      be useful for co-segregation studies in diabetic patients with and without severe
      clinical complications from their disease.

PMID- 8535075
TI  - Construction of a gene expression profile of a human fetal liver by single-pass
      cDNA sequencing.
AB  - We have obtained an overall gene expression profile of a human fetal liver by
      sequencing the 5' ends of random cDNA clones from an unbiased cDNA library. As a
      result, many novel genes that might be related to liver growth and hemopoiesis
      have been identified. Poly (A)+ RNA was purified from the liver of a human fetus
      obtained at the 22nd week of gestation, and a directional library was constructed
      with oligo d(T)-primed cDNAs synthesized without any normalizing procedures. The
      5' end of each randomly chosen clone was sequenced by the dideoxy-chain
      termination methods, and each sequence was used for homology search in the public
      databases such as GenBank, SWISS-PROT, and PIR. Of 1231 random cDNA clones
      analyzed, 697 clones representing 204 different transcripts (57%), were identical
      to previously known human genes. The spectrum of the genes in this category
      reflected well the physiological characteristics of the fetal liver, a
      combination of hepatic and hemopoietic functions. About 4% of the clones
      represented novel gene transcripts with significant homologies to known genes of
      human or other organisms. These included several genes that are known to be
      involved in cellular differentiation and/or proliferation. About 25% of the
      clones had no statistically significant match to any known genes. In summary, we
      have identified 546 different gene transcripts consisting of 204 known human
      genes, 42 homologous genes, and 300 unknown genes. Thus, this approach appears to
      be a highly efficient way to identify novel genes of biological interest.

PMID- 8535076
TI  - Cloning and regional localization of the mouse faciogenital dysplasia (Fgd1)
      gene.

PMID- 8535077
TI  - The first arch (Far) mutation in mice recombines with Hoxd and Mdk.

PMID- 8535078
TI  - A syntrophin gene maps to mouse chromosome 8 and is not the myodystrophy gene.

PMID- 8535079
TI  - Assignment of the paired box gene Pax1 to rat chromosome 3.

PMID- 8535080
TI  - Two polymorphic dinucleotide repeats in the rat dystrophin gene, including the
      conserved 3' UTR repeat.

PMID- 8535081
TI  - Reverse painting for identification of pig chromosomes in hybrid cell lines:
      assignment of the HOXB and the TK1 gene to pig chromosome 12p.

PMID- 8535082
TI  - Cloning and mapping of porcine OTF1 extends a synteny group conserved on SSC 4
      and HSA 1.

PMID- 8535083
TI  - Matrix-associated regions in haploid expressed domains.

PMID- 8535084
TI  - The 5' noncoding region of the mouse involucrin gene: comparison with the human
      gene and genes encoding other cornified envelope precursors.

PMID- 8535085
TI  - Mapping of two zinc finger protein genes to mouse chromosomes 4 and 7.

PMID- 8535086
TI  - Possible alternative splicing of the rat SA gene.

PMID- 8535087
TI  - Identification and characterization of a highly polymorphic microsatellite marker
      within the canine MHC class I region.

PMID- 8535088
TI  - Comparative mapping of sheep inhibin subunits alpha (INHA) and beta B(INHBB) to
      chromosome 2 in goat by FISH.

PMID- 8535089
TI  - Linkage analysis assignment of bovine granulocyte colony stimulating factor
      receptor (G-CSFR) to chromosome 3.

PMID- 8535090
TI  - Assignment of the bovine p53 gene (TP53) to chromosome 19q15 by fluorescence in
      situ hybridization.

PMID- 8535091
TI  - Localization of the somatostatin gene to bovine chromosome 1q23-q25 by in situ
      hydridization.

PMID- 8535092
TI  - Isolation and chromosomal location of Nsk1, a novel murine putative receptor
      tyrosine kinase.

PMID- 8535093
TI  - Implications of genetic variability of human beta 2-adrenergic receptor
      structure.

PMID- 8535094
TI  - Effects of endothelin receptor selective antagonists, BQ-123 and BQ-788, on IRL
      1620 and endothelin-1 responses of airway and vascular preparations from rats.
AB  - IRL 1620 (Suc-[Glu9, Ala11,15]ET-1(8-21), a selective ETB receptor agonist)
      contracted rat trachea and bronchus. The maximum response to IRL 1620 was less
      than that to endothelin-1 (ET-1) and, compared with ET-1 responses, IRL 1620
      responses reached equilibrium more quickly. IRL 1620 responses were antagonized
      by the selective ETB antagonist, BQ-788 (3 microM), but not by the selective ETA
      antagonist, BQ-123 (3 microM). ET-1 concentration-response curves were shifted
      only in the presence of both BQ-123 and BQ-788 (3 microM). In the presence of BQ
      123, the time course of ET-1 responses changed from being slow and sustained
      (ETA, see below) to being more like that to IRL 1620 (ETB). IRL 1620 did not
      contract pulmonary artery preparations from rats but ET-1 produced slow and
      sustained contractile responses which were antagonized by BQ-123 but not by BQ
      788. Thus, ET-1 contracts rat pulmonary artery and aorta predominantly via ETA
      receptors (responses blocked by BQ-123) and functional ETB receptors are unlikely
      to be present (no responses to IRL 1620). In contrast, ET-1 contracts rat trachea
      and bronchus via ETA and ETB receptors (tissues contracted to IRL 1620, ET-1
      responses were blocked by a combination of BQ-123 and BQ-788 and ET-1 responses
      resembled ETB in character when ETA receptors were blocked.

PMID- 8535095
TI  - Hyperresponsiveness to non-adrenergic, non-cholinergic vagal stimulation
      following multiple antigen challenge in guinea-pigs.
AB  - The role of airway inflammation, induced by weekly antigen challenge, in the
      airway hyperresponsiveness to vagal (whole and NANC components) nerve stimulation
      and to neurotransmitters (acetylcholine and selective agonists for tachykinin NK1
      and NK2 receptors) has been studied in the guinea-pig. Primarily, the time course
      (3, 7 and 14 days following the last challenge) of the effects of repeated
      aerosol antigen challenge on airway inflammation and bronchoalveolar fluid
      cellular composition was investigated. At 7 days following the last antigen
      challenge a maximal (as compared to 3 and 14 days) inflammatory response, in
      terms of a diffuse mild to marked infiltration of eosinophils, neutrophils and
      lymphocytes, was evident throughout pulmonary tissues. Only at this time some
      evidence of eosinophilia and neutropenia was detectable in BAL fluids. In these
      animals there was a normal bronchial responsiveness to iv administration of
      acetylcholine, selective synthetic agonists for the tachykinin NK2 receptors and
      capsaicin. On the other hand a remarkable airways hyperresponsiveness to iv
      administration of selective agonists for tachykinin NK1 receptors, as well as
      electrical stimulation of the vagal nerves (in presence and in absence of
      atropine), was detected. As a whole, these data indicate that at the peak of the
      inflammatory airway response following multiple antigen challenge there is a
      selective hyperresponsiveness to stimulation of vagal (mainly the non-adrenergic,
      non-cholinergic component) nerves associated with an increase in tachykinins (NK
      1)-mediated bronchospasm.

PMID- 8535096
TI  - The effects of tumour necrosis factor alpha on mediator release from human lung.
AB  - Although tumour necrosis factor alpha (TNF alpha) may be involved in the
      pathology of asthma, little is known about its role in mediator release from
      inflammatory cells in human lung. We investigated whether TNF alpha induced
      histamine release from mast cells in human chopped lung tissue and whether it
      modulated antigen-induced release of histamine and leukotrienes C4/D4/E4 from
      passively sensitized lung tissue. Spontaneous histamine release in the presence
      of 1 nM TNF alpha for up to 4 h at 37 degrees C was not significantly different
      from spontaneous histamine release alone (6.1 +/- 1.3% and 6.1 +/- 1.5% of total
      tissue histamine at 4h respectively; n = 3). Lung tissue was passively sensitized
      to the house dust mite Dermatophagoides pteronyssinus by incubating it in serum
      from an atopic volunteer donor for 3 h at 37 degrees C. Treatment of the
      sensitized lung tissue with 1 nM TNF alpha for 60 min prior to challenge with a
      low concentration (1.8 AU) of D. pteronyssinus caused a significant increase in
      the amount of histamine release induced by the antigen from 0.2 +/- 0.6% to 1.9
      +/- 1.0% of total tissue histamine (P = 0.045, n = 6). The release of leukotriene
      C4/D4/E4 induced by the same concentration of antigen was not significantly
      changed by the TNF alpha treatment (39.5 +/- 9.1 and 55.6 +/- 17.7 pg/100
      microliters supernatant sample respectively; n = 6). These results suggest that
      TNF alpha may be involved in potentiation of histamine release in allergic
      asthma, particularly in the presence of low antigen concentrations.

PMID- 8535097
TI  - The effect of selective phosphodiesterase inhibitors in comparison with other
      anti-asthma drugs on allergen-induced eosinophilia in guinea-pig airways.
AB  - The effects of isoenzyme selective phosphodiesterase (PDE) inhibitors and other
      anti-asthma drugs on antigen-induced eosinophil recruitment and activation in
      guinea-pig airways was studied. Guinea-pigs were sensitized and subsequently
      challenged with aerosolized ovalbumin (OVA). Bronchoalveolar lavage (BAL) was
      performed 24 h later. A significant increase in eosinophils and eosinophil
      peroxidase (EPO) was detected in BAL fluid and BAL fluid supernatant respectively
      from OVA immunized guinea-pigs compared with sham treated animals. Guinea-pigs
      were treated for 7 days prior to antigen challenge with either the following
      drugs or the appropriate vehicle (i.p.). The selective beta 2 agonist, salbutamol
      (0.3 mg/kg), the PDE III inhibitor, milrinone (15 mg/kg) and the non-selective
      PDE inhibitor, trequinsin (1 mg/kg) had no effect on eosinophil number or EPO
      levels. The PDE IV inhibitor, rolipram (15 mg/kg), the mixed type III/IV PDE
      inhibitor, benzafentrine (15 mg/kg) and the non-selective PDE inhibitor,
      aminophylline (31.5 mg/kg) had no effect on eosinophil number but reduced the
      amount of EPO detected. The anti-inflammatory glucocorticosteroids,
      beclomethasone (10 mg/kg) and betamethasone (4 mg/kg) and the type IV PDE
      inhibitor, RP 73401 (5 mg/kg) reduced both eosinophil numbers and EPO levels.
      These results suggest a role for the type IV PDE isoenzyme in the control of
      eosinophil recruitment and possibly activation in the airways.

PMID- 8535098
TI  - The maintenance of functional activity in human isolated bronchus after
      cryopreservation.
AB  - Cryopreservation has been successfully used in the in vitro study of
      pharmacological responses of animal tissues and, to a limited extent, of human
      tissue. In this study, we examined the effect of cryopreservation on reactivity
      of human bronchus which was stored for a period of up to 3 weeks. Thirty-two
      bronchial rings were obtained from each of four transplantation donors (four
      male, aged 32 +/- 15 years SD). Eight rings from each patient were studied on day
      0 (the day of retrieval) and an additional eight on days 7, 14 and 21, after
      cryopreservation in 1.8 M dimethyl sulfoxide in 1 ml foetal bovine serum at -190
      degrees C. On day 0, all tissues from all patients contracted in response to
      either histamine or carbachol or relaxed in response to isoprenaline or
      levcromakalim. There was no significant difference in the mean Tmax or pD2 values
      for any agonist on days 7, 14 and 21 when responses were compared with those
      obtained on day 0. The major change induced by cryopreservation was observed in
      the response to antigen. Tissues from three of the four donors contracted to the
      administration of Dermatophagoides pteronyssinus on day 0. However, when tissues
      from these same donors were studied on days 7, 14 and 21, they did not contract
      to this antigen. The results of this study indicate that human bronchial tissue
      may be successfully cryopreserved to maintain contractile and relaxant responses
      to various agonists. However, the response to antigen in tissues, which on day 0
      of study were determined to be sensitized, was not present after
      cryopreservation.

PMID- 8535099
TI  - Effect of angiotensin converting enzyme inhibition on airway conductance during
      hypocapnic hyperventilation in normal subjects.
AB  - In nine normal subjects, specific airway conductance was measured by whole body
      plethysmography before and immediately after hypocapnic hyperventilation. This
      procedure, forced expiratory manoeuvres and arterial blood pressure measurements
      were carried out before and 4 h after placebo and the angiotensin converting
      enzyme inhibitor, enalapril, in a double-blind, randomized study design.
      Bronchoconstriction to hypocapnic hyperventilation was shown by a reduction in
      specific airway conductance on all occasions (P < 0.001). A reduction in mean
      blood pressure was obtained after enalapril compared to placebo (P < 0.05). No
      significant change attributable to enalapril was observed in any lung function
      measurement either at rest or immediately after hypocapnic hyperventilation,
      despite an expected enhancement of endogenous angiotensin converting enzyme
      activity by alkalosis. Inhibition of angiotensin converting enzyme revealed no
      effect of the endogenous activity of this enzyme on airway calibre either at rest
      or during the bronchoconstrictor response to hypocapnic hyperventilation.

PMID- 8535101
TI  - From Russia with love.

PMID- 8535100
TI  - Allergen-induced glycoconjugate secretion in guinea-pig trachea in vivo:
      modulation by indomethacin, BW B70C and ZD-2138.
AB  - A method has been established for measurement of tracheal secretions in
      anaesthetized, ventilated guinea-pigs. The upper trachea was cannulated and
      perfused with saline. The perfusate was analysed for protein using the Lowry
      assay and for glycoconjugates ('mucus') by a procedure generating a fluorophore
      from fucose moieties in the sample. Intravenously infused acetylcholine (ACh)
      stimulated an increase in glycoconjugate secretion which was maximal after 75 min
      of ACh administration. Total protein concentration was not increased.
      Intravenously infused 15-HETE produced a similar increase in glycoconjugate
      secretion also without increasing protein concentration, but the time of maximal
      effect was earlier (30 min) than with ACh. Intravenous infusion of allergen
      (ovalbumin) in antihistamine pretreated, sensitized animals induced a dose
      related glycoconjugate secretion which was maximal at 30 min after challenge.
      Indomethacin potentiated allergen-induced glycoconjugate secretion. The
      reportedly specific inhibitor of 5-lipoxygenase, ZD-2138, substantially inhibited
      allergen-induced pulmonary bronchoconstriction but did not influence
      glycoconjugate secretion. In contrast, the selective 5-, 15-lipoxygenase
      inhibitor BW B70C significantly attenuated both allergic airway closure and
      glycoconjugate secretion. These studies demonstrate the practicability of
      measuring glycoconjugate secretion in guinea-pig trachea in vivo, and that ACh
      and 15-HETE are potent secretagogues in this species. Further, they suggest that
      allergic glycoconjugate secretion is mediated, at least in part, via the release
      of lipid mediators from pathways other than via 5-lipoxygenase.

PMID- 8535102
TI  - Announcing a new graduate program in holistic health nursing practice.

PMID- 8535103
TI  - AHNA and certification.

PMID- 8535104
TI  - Low morale among qualified nurses: action needed.

PMID- 8535105
TI  - UKCC's standards for incorporation into contracts.

PMID- 8535106
TI  - Prescribing practice of take-home analgesia for day case surgery.
AB  - Postoperative pain following day surgery is a common problem. The prescription of
      appropriate analgesia with clear instructions for the patient is crucial. This
      article examines the effect of changing prescribing practice, backed up by a
      patient information leaflet, on the effectiveness of take-home analgesia after
      day case surgery.

PMID- 8535107
TI  - The future of mental health nurses in liaison psychiatry.
AB  - This article examines the current status of the mental health nurse in liaison
      psychiatry. A model for practice is put forward and the need for a cohesive
      educational framework is argued.

PMID- 8535108
TI  - Intermittent self-catheterisation: research-based practice.
AB  - Intermittent self-catheterisation (ISC) is an effective management strategy for
      people who have urinary retention or postvoid residual due to urethral sphincter
      or detrusor dysfunction. However, some questions still need to be answered on the
      details of ISC. This article presents current research findings that may resolve
      some of the practice issues and suggests that nurses are in a prime position to
      implement research-based practice.

PMID- 8535109
TI  - Learning to respond to disclosure of child sexual abuse.

PMID- 8535110
TI  - Child sexual abuse: helping children and their families.
AB  - The reality of child sexual abuse has only recently been accepted by
      professionals. Previously, treatment strategies were aimed at adult survivors
      rather than at children. Treatment programmes for children have a short history
      and their long-term effects cannot be validated yet, although some attempts have
      been made (Bentovim et al, 1987).

PMID- 8535111
TI  - Children's views about health: assessing the implications for nurses.
AB  - This article explores how children, in interacting with parents, peers and
      others, acquire their beliefs about health and health-related matters and
      examines children's lay health beliefs of the importance of ethnicity in
      structuring their views. These themes are developed in interviews with children
      about health and health-related matters. The views which emerge are discussed in
      relation to their implications for nurses.

PMID- 8535112
TI  - Needs of visitors in the intensive care unit.
AB  - Visitors are defined as biological relatives and significant others, including
      friends and partners. Meeting the needs of visitors will reduce their stress
      levels. Nurses have an important role to play in meeting visitors' needs.
      Visitors needs can be categorised as: informational, emotional, personal,
      physical, and environmental.

PMID- 8535113
TI  - Nursing care of a superficial incisional surgical site infection.
AB  - There is a wealth of literature on surgical wound infection, but surprisingly
      little on the nursing management of superficial incisional wound infection. This
      article aims to define superficial incisional wound infection and details common
      management strategies.

PMID- 8535114
TI  - Nursing skills and practice.
AB  - This article discusses the value placed on basic nursing skills and practice in
      preregistration diploma programmes (Project 2000). The authors argue that the
      current emphasis on the early acquisition of theoretical knowledge must not
      underestimate the importance of practising basic skills for the development of
      students' confidence in clinical settings.

PMID- 8535115
TI  - Key characteristics of nursing development units.

PMID- 8535116
TI  - Nursing care that patients value.
AB  - The delivery of nursing care should be based on meeting patients' individual
      needs. This article presents the findings of a small-scale study which explored
      the feelings that people express regarding the care they would like and receive
      from nurses.

PMID- 8535117
TI  - How can community care tragedies be avoided?

PMID- 8535118
TI  - Identifying people with learning disabilities who have been sexually abused.

PMID- 8535119
TI  - Fast-track care after cardiac surgery.
AB  - This article explains the rationale for fast-track management of low-risk cardiac
      surgical patients and describes the selection process and care received by these
      patients at the Royal Brompton Hospital. A review of the fast-track audit is
      presented and discussed.

PMID- 8535120
TI  - Coronary care unit ST-trending system: interpreting complex output data.
AB  - Analysis of the ST segment is an accepted part of the assessment of coronary
      ischaemia. Traditionally, such analysis has been applied to 12-lead surface
      electrocardiograms, but it is increasingly applied to 24-hour Holter recordings
      and bedside monitoring systems, using complex computer algorithms. There is a
      potential for results to be misleading as a consequence of uncritical acceptance
      of complex medical data processing.

PMID- 8535121
TI  - Assisting patients living with long-term oxygen therapy.
AB  - The nurse has an important role in assisting chronically ill patients disabled by
      breathlessness to adjust to long-term oxygen therapy. This article provides a
      simplified summary of the changed physiology necessitating additional oxygen. The
      focus, however, is on nursing and the educational and rehabilitation strategies
      that may be used to support patients in living with long-term oxygen therapy.

PMID- 8535122
TI  - The case for village communities for people with learning disabilities.
AB  - This article puts forward the arguments for the establishment of village
      communities for some people with learning disabilities (mental handicap) and
      shows how they can provide a safe living environment for residents, while at the
      same time enhancing their quality of life.

PMID- 8535123
TI  - Sexuality and people with learning disabilities.
AB  - Despite the excellent pioneering work of the Family Planning Association and
      Brook Advisory Centres, sexuality and people with learning disabilities remains a
      largely unexplored area (Brandon, 1990). This article highlights the need for
      such individuals to receive sex education alongside social education. It is
      proposed that learning disability nurses are the most suitable health-care
      professionals to be the primary educators on such issues because of their
      expertise and unique relationships with their clients.

PMID- 8535124
TI  - Ward manager systems in learning disability services.
AB  - Drawing on two separate research projects, this article examines the ward manager
      system within learning disability services and highlights issues for
      consideration by services about to embark on such systems.

PMID- 8535125
TI  - Role of questioning skills in patient assessment.
AB  - This article is a critical analysis of the literature on patient assessment,
      nurses' questioning skills and effective methods of teaching questioning skills.
      Current practice and rituals are highlighted and recommendations regarding the
      search for excellence are included.

PMID- 8535126
TI  - Maintaining nurses' job satisfaction and morale.
AB  - In this article those factors which influence the job satisfaction and morale of
      nurses are considered. It is suggested that action is needed if the profession is
      to continue to grow and develop.

PMID- 8535127
TI  - Opportunities and obstructions for enrolled nurses.

PMID- 8535128
TI  - Living wills: how do they inform care?
AB  - Recent publicity about living wills has heightened nurses' awareness about the
      growing number of patients and clients completing them. However, there appears to
      be considerable confusion and growing anxiety about the legality of living wills
      as documents, the authority they have in informing care, and the role of health
      care professionals in using them.

PMID- 8535129
TI  - Is restricted visiting in conflict with patients' needs?
AB  - This article explores the issue of restricted visiting in coronary care units and
      questions whether this practice is in conflict with individualised patient care.
      After reviewing the literature on this subject, it proposes that the practice of
      such restricted visiting should be addressed.

PMID- 8535130
TI  - Law series: 14. Children: proceedings for care or supervision orders.

PMID- 8535131
TI  - Arabidopsis in Madison: genes and phenotypes spread like weeds.

PMID- 8535133
TI  - The Arabidopsis AGL8 MADS box gene is expressed in inflorescence meristems and is
      negatively regulated by APETALA1.
AB  - MADS box genes encode putative transcription factors that play important roles in
      plant and animal development. In plants, MADS box genes are involved in the early
      step of specifying floral meristem identity as well as the later step of
      determining the fate of floral organ primordia. Here, we describe the isolation
      and characterization of a new MADS box gene from Arabidopsis, designated AGL8.
      Although AGL8 RNA does not accumulate during vegetative growth, it accumulates to
      high levels in the inflorescence apical meristem as well as in the inflorescence
      stem and cauline leaves. AGL8 RNA is excluded from the young flower primordia
      that arise on the flanks of the inflorescence meristem but later accumulates in
      the walls of the developing carpels. The lack of AGL8 RNA in floral meristems is
      due in part to the action of another MADS box gene, APETALA1, because AGL8 RNA
      does accumulate in apetala1 mutant flower primordia.

PMID- 8535132
TI  - Light control of seedling morphogenetic pattern.

PMID- 8535134
TI  - Ectopic expression of the Arabidopsis transcriptional activator Athb-1 alters
      leaf cell fate in tobacco.
AB  - The Arabidopsis thaliana Athb-1 is a homeobox gene of unknown function. By
      analogy with homeobox genes of other organisms, its gene product, Athb-1, is most
      likely a transcription factor involved in developmental processes. We constructed
      a series of Athb-1-derived genes to examine the roles of Athb-1 in
      transcriptional regulation and plant development. Athb-1 was found to
      transactivate a promoter linked to a specific DNA binding site by transient
      expression assays. In transgenic tobacco plants, overexpression of Athb-1 or its
      chimeric derivatives with heterologous transactivating domains of the yeast
      transcription factor GAL4 or herpes simplex virus transcription factor VP16
      conferred deetiolated phenotypes in the dark, including cotyledon expansion, true
      leaf development, and an inhibition of hypocotyl elongation. Expression of Athb-1
      or the two chimeric derivatives also affected the development of palisade
      parenchyma under normal growth conditions, resulting in light green sectors in
      leaves and cotyledons, whereas other organs in the transgenic plants remained
      normal. Both developmental phenotypes were induced by glucocorticoid in
      transgenic plants expressing a chimeric transcription factor comprising the Athb
      1 DNA binding domain, the VP16 transactivating domain, and the glucocorticoid
      receptor domain. Plants with severe inducible phenotypes showed additional
      abnormality in cotyledon expansion. Our results suggest that Athb-1 is a
      transcription activator involved in leaf development.

PMID- 8535135
TI  - Isolation and characterization of an Arabidopsis mutant deficient in the
      thylakoid lipid digalactosyl diacylglycerol.
AB  - The galactolipids monogalactosyl and digalactosyl diacylglycerol occur in all
      higher plants and are the predominant lipid components of chloroplast membranes.
      They are thought to be of major importance to chloroplast morphology and
      physiology, although direct experimental evidence is still lacking. The enzymes
      responsible for final assembly of galactolipids are associated with the envelope
      membranes of plastids, and their biochemical analysis has been notoriously
      difficult. Therefore, we have chosen a genetic approach to study the biosynthesis
      and function of galactolipids in higher plants. We isolated a mutant of
      Arabidopsis that is deficient in digalactosyl diacylglycerol by directly
      screening a mutagenized M2 population for individuals with altered leaf lipid
      composition. This mutant carries a recessive nuclear mutation at a single locus
      designated dgd1. Backcrossed mutants show stunted growth, pale green leaf color,
      reduced photosynthetic capability, and altered thylakoid membrane ultrastructure.

PMID- 8535136
TI  - The large-scale genomic organization of repetitive DNA families at the telomeres
      of rye chromosomes.
AB  - Repetitive DNA sequences in the terminal heterochromatin of rye (Secale cereale)
      chromosomes have consequences for the structural and functional organization of
      chromosomes. The large-scale genomic organization of these regions was studied
      using the telomeric repeat from Arabidopsis and clones of three nonhomologous,
      tandemly repeated, subtelomeric DNA families with complex but contrasting higher
      order structural organizations. Polymerase chain reaction analysis with a single
      primer showed a fraction of the repeat units of one family organized in a "head
      to-head" orientation. Such structures suggest evolution of chromosomes by
      chromatid-type breakage-fusion-bridge cycles. In situ hybridization and pulse
      field gel electrophoresis showed the order of the repeats and the heterogeneity
      in the lengths of individual arrays. After Xbal digestion and pulse field gel
      electrophoresis, the telomeric and two subtelomeric clones showed strong
      hybridization signals from 40 to 100 kb, with a maximum at 50 to 60 kb. We
      suggest that these fragments define a basic higher order structure and DNA loop
      domains of regions of rye chromosomes consisting of arrays of tandemly organized
      sequences.

PMID- 8535137
TI  - Seed coat-associated invertases of fava bean control both unloading and storage
      functions: cloning of cDNAs and cell type-specific expression.
AB  - We have studied the molecular physiology of photosynthate unloading and
      partitioning during seed development of fava bean (Vicia faba). During the
      prestorage phase, high levels of hexoses in the cotyledons and the apoplastic
      endospermal space are correlated with activity of cell wall-bound invertase in
      the seed coat. Three cDNAs were cloned. Sequence comparison revealed genes
      putatively encoding one soluble and two cell wall-bound isoforms of invertase.
      Expression was studied in different organs and tissues of developing seeds by RNA
      gel analysis, in situ hybridization, enzyme assay, and enzyme activity staining.
      One extracellular invertase gene is expressed during the prestorage phase in the
      thin-walled parenchyma of the seed coat, a region known to be the site of
      photoassimilate unloading. We propose a model for an invertase-mediated unloading
      process during early seed development and the regulation of cotyledonary sucrose
      metabolism. After unloading from the seed coat, sucrose is hydrolyzed by cell
      wall-bound invertases. Thus, invertase contributes to establish sink strength in
      young seeds. The resultant hexoses are loaded into the cotyledons and control
      carbohydrate partitioning via an influence on the sucrose synthase/sucrose
      phosphate synthase pathway. The developmentally regulated degradation of the thin
      walled parenchyma expressing the invertase apparently initiates the storage
      phase. This is characterized by a switch to a low sucrose/hexoses ratio. Feeding
      hexoses to storage-phase cotyledons in vitro increases the sucrose-phosphate
      synthase/sucrose synthase ratio and changes carbohydrate partitioning in favor of
      sucrose. Concomitantly, the transcript level of the major storage product legumin
      B is downregulated.

PMID- 8535138
TI  - The D-type alfalfa cyclin gene cycMs4 complements G1 cyclin-deficient yeast and
      is induced in the G1 phase of the cell cycle.
AB  - Cyclins are key regulators of the cell cycle in all eukaryotes. In alfalfa, we
      have previously isolated three B-type cyclins. The closely related cycMs1 and
      cycMs2 genes are expressed primarily during the G2 and M phases and are most
      likely mitotic cyclins; expression of the cycMs3 gene is induced in the G0-to-G1
      transition, when cells reenter the cell cycle. By complementation of G1 cyclin
      deficient yeast cells, a novel alfalfa cyclin, designated cycMs4, was isolated.
      The predicted amino acid sequence of the cycMs4 gene is most similar to that of
      the Arabidopsis cyclin delta 3 gene. CycMs4 and cyclin delta 3 belong to the
      class of D-type cyclins and contain PEST-rich regions and a retinoblastoma
      binding motif. When comparing expression levels in different organs, cycMs4
      transcripts were present predominantly in roots. Whereas expression of the cycMs4
      gene was cell cycle-regulated in suspension-cultured cells, transcription in
      roots was observed to depend also on the positional context of the cell. When
      differentiated G0-arrested leaf cells were induced to resume cell division by
      treatment with plant hormones, cycMs4 transcription was induced before the onset
      of DNA synthesis. Whereas this induction was preceded by that of the cycMs3 gene,
      cycMs2 expression occurred later and at the same time as mitotic activity. These
      data suggest that cycMs4 plays a role in the G1-to-S transition and provide a
      model to investigate the plant cell cycle at the molecular level.

PMID- 8535139
TI  - The petunia MADS box gene FBP11 determines ovule identity.
AB  - In contrast to the wealth of information relating to genes regulating floral
      meristem and floral organ identity, only limited data are available concerning
      genes that are involved in determining and regulating the identity and
      development of an ovule. We have recently isolated the floral binding protein 11
      (FBP11) MADS box gene from petunia and found that it is expressed exclusively in
      ovule primordia and subsequently in the ovules, suggesting a role for this gene
      in ovule formation. To test this hypothesis, we constructed a recombinant gene in
      which the full-size FBP11 cDNA was placed under the control of a strong
      cauliflower mosaic virus 35S promoter. Transgenic petunia plants expressing this
      chimeric gene have ovulelike structures on the adaxial side of the sepals and the
      abaxial side of the petals. Detailed morphological studies showed that these
      ovulelike structures are true ovules. RNA gel blot analysis was performed to
      investigate ectopic FBP11 expression in relation to the expression of the closely
      related FBP7 gene and the putative petunia class C-type homeotic genes FBP6 and
      pMADS3. Our results indicate that FBP11 represents an ovule identity gene. A new
      model describing the mode of action of FBP11 as an additional class D MADS box
      gene is presented.

PMID- 8535140
TI  - The cAMP-dependent protein kinase catalytic subunit is required for appressorium
      formation and pathogenesis by the rice blast pathogen Magnaporthe grisea.
AB  - Magnaporthe grisea, the causal agent of rice blast disease, differentiates a
      specialized infection cell, an appressorium, that is required for infection of
      its host. Previously, cAMP was implicated in the endogenous signaling pathway
      leading to appressorium formation. To obtain direct evidence for the role of cAMP
      in appressorium formation, the gene encoding the catalytic subunit of the cAMP
      dependent protein kinase (cpkA) was cloned, sequenced, and disrupted. Polymerase
      chain reaction primers designed after highly conserved regions in the same gene
      from other organisms were used to amplify genomic DNA fragments. The cloned
      amplification products were used to identify genomic clones. DNA blot analysis
      indicated that cpkA is present as a single copy in the genome. cpkA consists of
      1894 bp, including three short introns sufficient to encode a protein of 539
      amino acids with a predicted molecular mass of 60.7 kD. The deduced peptide
      shares > 45% identity with other catalytic subunits and contains all functional
      motifs and residues with the addition of a glutamine-rich region at the N
      terminus. Two transformants, L5 and T-182, in which cpkA had been replaced with a
      hygromycin resistance gene cassette, were unable to produce appressoria, could
      not be induced to form appressoria by cAMP, and were nonpathogenic on susceptible
      rice, even when leaves were abraded. These results were confirmed by analysis of
      57 progeny from a cross between transformant L5 and the wild-type laboratory
      strain 70-6. Other aspects of growth and development, including vegetative growth
      as well as asexual and sexual competence, were unaffected when measured in vitro.
      These results provide direct evidence that the cAMP-dependent protein kinase is
      necessary for infection-related morphogenesis and pathogenesis in a
      phytopathogenic fungus.

PMID- 8535141
TI  - Gibberellin-regulated expression of a myb gene in barley aleurone cells: evidence
      for Myb transactivation of a high-pI alpha-amylase gene promoter.
AB  - Functional analysis of a barley high-pI alpha-amylase gene promoter has
      identified a gibberellin (GA) response complex in the region between -174 and 
      108. The sequence of the central element, TAACAAA, is very similar to the c-Myb
      and v-Myb consensus binding site. We investigated the possibility that a GA
      regulated Myb transactivates alpha-amylase gene expression in barley aleurone
      cells. A cDNA clone, GAmyb, which encodes a novel Myb, was isolated from a barley
      aleurone cDNA library. RNA blot analysis revealed that GAmyb expression in
      isolated barley aleurone layers is up-regulated by GA. The kinetics of GAmyb
      expression indicates that it is an early event in GA-regulated gene expression
      and precedes alpha-amylase gene expression. Cycloheximide blocked alpha-amylase
      gene expression but failed to block GAmyb gene expression, indicating that
      protein synthesis is not required for GAmyb gene expression. Gel mobility shift
      experiments with recombinant GAMyb showed that GAMyb binds specifically to the
      TAACAAA box in vitro. We demonstrated in transient expression experiments that
      GAMyb activates transcription of a high-pI alpha-amylase promoter fused to a beta
      glucuronidase reporter gene in the absence of GA. Our results indicate that the
      GAMyb is the sole GA-regulated transcription factor required for transcriptional
      activation of the high-pI alpha-amylase promoter. We therefore postulate that
      GAMyb is a part of the GA-response pathway leading to alpha-amylase gene
      expression in aleurone cells.

PMID- 8535142
TI  - Induction of wound response genes in tomato leaves by bestatin, an inhibitor of
      aminopeptidases.
AB  - Bestatin, an inhibitor of some aminopeptidases in plants and animals, is a
      powerful inducer of defense genes in tomato leaves; these genes are also induced
      by herbivore attacks, mechanical wounding, systemin, and methyl jasmonate. Unlike
      wounding and systemin, bestatin does not cause an increase in intracellular
      jasmonic acid concentrations, and inhibitors of the octadecanoid pathway do not
      inhibit induction by bestatin. Furthermore, defense genes were induced by
      bestatin in a mutant tomato line (JL-5) with a defect in the octadecanoid
      pathway. Bestatin therefore appears to be exerting its effects close to the level
      of transcriptional control of these genes, where it may be inhibiting a
      regulatory protease.

PMID- 8535143
TI  - The Arabidopsis Adh gene exhibits diverse nucleosome arrangements within a small
      DNase I-sensitive domain.
AB  - The alcohol dehydrogenase (Adh) gene from Arabidopsis shows enhanced sensitivity
      to DNase I in cells that express the gene. This generalized sensitivity to DNase
      I is demarcated by position -500 on the 5' side and the end of the mRNA on the 3'
      side. Thus, the gene defined as the promoter and mRNA coding region corresponds
      very closely in size with the gene defined as a nuclease-sensitive domain. This
      is a remarkably close correspondence between a sensitive domain and a eukaryotic
      transcriptional unit, because previously reported DNase I-sensitive domains
      include large regions of DNA that are not transcribed. Nucleosomes are present in
      the coding region of the Adh gene when it is expressed, indicating that the
      transcriptional elongation process causes nucleosome disruption rather than
      release of nucleosomes from the coding region. In addition, the regulatory region
      contains a loosely positioned nucleosome that is separated from adjacent
      nucleosomes by internucleosomic DNA segments longer than the average linker DNA
      in bulk chromatin. This specific array of nucleosomes coexists with bound
      transcription factors that could contribute to the organization of the nucleosome
      arrangement. These results enhance our understanding of the complex interactions
      among DNA, nucleosomes, and transcription factors during gene expression in
      plants.

PMID- 8535144
TI  - Inhibition of maize histone deacetylases by HC toxin, the host-selective toxin of
      Cochliobolus carbonum.
AB  - HC toxin, the host-selective toxin of the maize pathogen Cochliobolus carbonum,
      inhibited maize histone deacetylase (HD) at 2 microM. Chlamydocin, a related
      cyclic tetrapeptide, also inhibited HD activity. The toxins did not affect
      histone acetyltransferases. After partial purification of histone deacetylases
      HD1-A, HD1-B, and HD2 from germinating maize embryos, we demonstrated that the
      different enzymes were similarly inhibited by the toxins. Inhibitory activities
      were reversibly eliminated by treating toxins with 2-mercaptoethanol, presumably
      by modifying the carbonyl group of the epoxide-containing amino acid Aeo (2-amino
      9,10-epoxy-8-oxodecanoic acid). Kinetic studies revealed that inhibition of HD
      was of the uncompetitive type and reversible. HC toxin, in which the epoxide
      group had been hydrolyzed, completely lost its inhibitory activity; when the
      carbonyl group of Aeo had been reduced to the corresponding alcohol, the modified
      toxin was less active than native toxin. In vivo treatment of embryos with HC
      toxin caused the accumulation of highly acetylated histone H4 subspecies and
      elevated acetate incorporation into H4 in susceptible-genotype embryos but not in
      the resistant genotype. HDs from chicken and the myxomycete Physarum polycephalum
      were also inhibited, indicating that the host selectivity of HC toxin is not
      determined by its inhibitory effect on HD. Consistent with these results, we
      propose a model in which HC toxin promotes the establishment of pathogenic
      compatibility between C. carbonum and maize by interfering with reversible
      histone acetylation, which is implicated in the control of fundamental cellular
      processes, such as chromatin structure, cell cycle progression, and gene
      expression.

PMID- 8535145
TI  - Identification, characterization, and purification of a tobacco endonuclease
      activity induced upon hypersensitive response cell death.
AB  - Programmed cell death (pcd) is activated during the hypersensitive response (HR)
      of plants to avirulent pathogens. We have recently shown that, similar to pcd in
      animal cells, nuclei of cells undergoing HR cell death contain fragmented nuclear
      DNA (nDNA). Here, we report that cell death occurring during the HR is
      accompanied by an increase in the activity of several deoxyribonucleases.
      Induction of nuclease activities was coordinated with cell death and may account
      for the degradation of nDNA during the HR. HR-associated nuclease activities were
      not induced during senescence, following necrotic cell death resulting from
      abiotic stress, or in response to induction of plant defense mechanisms by
      salicylic acid. HR-associated nuclease activities were stimulated by Ca2+ and
      inhibited by EGTA, EDTA, and Zn2+. At least one of the HR-associated nuclease
      activities was detected in nuclei purified from leaves undergoing pcd. A nuclease
      with an electrophoretic mobility similar to that of the nuclease activity found
      in nuclei isolated from leaves undergoing HR cell death was purified. Our
      findings are in accordance with some of the biochemical events that occur during
      pcd in animal cells. However, further analysis of the pattern of nDNA
      fragmentation and the corresponding structural changes that occur in the nuclei
      of tobacco cells undergoing HR cell death revealed that these features may have
      differences from those that take place during apoptosis in animal cells.

PMID- 8535146
TI  - The lysine-dependent stimulation of lysine catabolism in tobacco seed requires
      calcium and protein phosphorylation.
AB  - The accumulation of free lysine in tobacco seed triggers the stimulation of
      lysine-ketoglutarate reductase, an enzyme that acts in lysine catabolism. The
      mechanism of lysine-ketoglutarate reductase stimulation was studied in two
      different systems: (1) developing seeds of wild-type plants in which the low
      basal lysine-ketoglutarate reductase activity can be stimulated by the exogenous
      addition of lysine; and (2) developing seeds of transgenic tobacco plants
      expressing a bacterial dihydrodipicolinate synthase in which lysine-ketoglutarate
      reductase activity is stimulated by endogenous lysine overproduction. In both
      systems, the stimulation of lysine-ketoglutarate reductase activity was
      significantly reduced when treated with the Ca2+ chelator EGTA. Moreover, the
      inhibitory effect of EGTA was overcome by the addition of Ca2+ but not Mg2+,
      suggesting that the lysine-dependent activation of lysine-ketoglutarate reductase
      requires Ca2+. This was further confirmed by a significant stimulation of lysine
      ketoglutarate reductase activity following the treatment of wild-type seeds with
      ionomycin (an ionophore that increases Ca2+ flow into the cytoplasm). In
      addition, treatment of wild-type seeds with the protein phosphatase inhibitor
      okadaic acid triggered a significant induction in lysine-ketoglutarate reductase
      activity, whereas treatment of the transgenic seeds with the protein kinase
      inhibitor K-252a caused a significant reduction in its activity. Thus, we
      conclude that the stimulation of lysine-ketoglutarate reductase activity by
      lysine in tobacco seed operates through an intracellular signaling cascade
      mediated by Ca2+ and protein phosphorylation.

PMID- 8535147
TI  - Requirements for optimal expression of secreted and nonsecreted recombinant
      proteins in vaccinia virus systems.
AB  - Selection of an optimal promoter is necessary for efficient expression of foreign
      genes with vaccinia virus. Since a variety of powerful (homologous) vaccinia
      virus promoters and foreign (heterologous) promoter systems have been described
      for use in vaccinia, we have addressed the question of whether a general rule
      exists that allows the prediction of the optimal promoter/gene combination. We
      have compared the expression properties of four secreted proteins, the human
      blood clotting factor IX (FIX), the human blood glycoprotein Protein S (ProtS),
      the human von Willebrand factor (vWF), and the Hepatitis B virus (HBV) middle
      surface glycoprotein preS2, with proteins that were reported not to be secreted,
      the HBV large surface glycoprotein preS1 and the murine leukemia virus (MuLV) BM
      5 Eco gag protein. In addition, we have included in our study an internal control
      protein, the vaccinia virus p11 protein, to monitor possible side effects of the
      promoter system used. Genes encoding the foreign proteins were placed either
      under control of a synthetic vaccinia virus early/late promoter (selP) or under
      control of the bacteriophage T7 promoter (T7/emc system). The secreted proteins
      were more efficiently expressed when fused to the homologous promoter. Direct
      comparison of the two promoters indicated that the expression level ranged
      between 1.4 (ProtS) and 3.9 (FIX)-fold higher with the selP than with the T7
      promoter. In contrast, the cell-associated HBV preS1 was more efficiently
      expressed under the T7 promoter and the MuLV BM-5 Eco gag polypeptide was
      expressed equally well from both promoters. These data indicate that a careful
      prediction of optimal promoter/foreign gene combinations for the vaccinia virus
      expression system is possible. The choice of the optimal promoter/expression
      system is based on a simple classification scheme, discriminating secreted and
      nonsecreted proteins.

PMID- 8535148
TI  - Production of lipidated meningococcal transferrin binding protein 2 in
      Escherichia coli.
AB  - Neisseria meningitidis strains grown under iron starvation conditions produce
      transferrin binding proteins (Tbp1 and Tbp2) which have been shown to play a
      major role in iron acquisition. Recent studies performed with Tbp2 purified from
      N. meningitidis suggest that this surface protein is a potential vaccine
      component. In order to further evaluate the immunogenicity of Tbp2, it was
      essential to develop a heterologous expression system to generate high amounts of
      purified protein. Tbp2 is produced in Neisseria as a precursor with a signal
      peptide whose cleavage follows a lipidation step on a cysteine residue which is
      the first amino acid in the mature protein. When produced in Escherichia coli
      with its natural signal peptide, a high amount of Tbp2 (about 10% of total cell
      proteins) was detected. However, most of the protein was nonlipidated precursor
      and only a small fraction was mature Tbp2. In order to optimize the maturation of
      the precursor, the natural signal sequence was replaced by several E. coli
      lipoprotein signal peptides. Expression levels and maturation of the precursor
      were highly variable depending on the signal peptide used. With one of these, an
      efficient maturation and a high amount of mature lipidated Tbp2 were obtained
      (about 3% of total cell proteins). A large-scale production process was then
      established for this E. coli-produced Tbp2.

PMID- 8535149
TI  - Cytoplasmic and periplasmic production of human placental glutathione transferase
      in Escherichia coli.
AB  - An expression vector yielding large amounts of GST P1-1 in the cytoplasm of
      Escherichia coli was constructed. The recombinant enzyme, obtained after
      purification, was characterized in its physicochemical and kinetic properties and
      appeared to be indistinguishable from that purified from human placenta. However,
      N-terminal amino acid sequencing revealed that about 50% of the recombinant GST
      still contained methionine as the N-terminal amino acid. Such an incomplete
      processing was not simply due to overproduction of GST. In fact, under growth
      conditions that lead to a sharp decrease in the production of the protein the N
      terminal methionine was not removed. GST was unable to translocate across the
      bacterial membrane when it was fused to the leader peptide of the pelB gene from
      Erwinia carotovora and accumulated in the cytoplasm in a soluble and active
      conformation. However, when this fusion protein was produced in a bacterial
      strain overexpressing the bacterial chaperonins GroEL and GroES, a fraction of
      GST was exported into the periplasmic space with the correct N-terminal sequence.
      The yield of correctly processed GST accounted for 12% of total GST present in
      the E. coli cells. Our results suggest that chaperonins are able to interact with
      nascent GST, thus maintaining the protein in an export-competent form and that E.
      coli strains with enhanced secretory characteristics may be obtained by genetic
      engineering technology.

PMID- 8535150
TI  - Biologically active recombinant rat granulocyte macrophage colony-stimulating
      factor produced in Escherichia coli.
AB  - Rat granulocyte macrophage colony-stimulating factor (rGM-CSF) cDNA was amplified
      and cloned, and recombinant-rGM-CSF (R-rGM-CSF) was expressed and isolated from
      Escherichia coli. The synthesis of R-rGM-CSF was directed by a modified,
      inducible maltose binding protein (MBP) gene fusion expression vector, pMTR-23,
      and secreted to the periplasm. The vector pMTR-23 contains a new multiple cloning
      site encoding a unique thrombin-sensitive cleavage site and short spacer arm
      which facilitates separation of the MBP from the foreign protein domain of hybrid
      proteins. Biologically active R-rGM-CSF was rapidly purified by a combination of
      affinity and ion exchange chromatography, with a yield of 1.5 mg of R-rGM-CSF per
      liter of cultured cells. The purified R-rGM-CSF, like the native molecule,
      exhibits potent biological activity in two rGM-CSF-specific assays, considerably
      enhancing the accessory activity of rat dendritic cells and stimulating the
      differentiation of dendritic cells from fresh cultures of rat bone marrow cells.
      Although dendritic cells are difficult to isolate from tissues, the availability
      of R-rGM-CSF should now facilitate the development of large numbers of dendritic
      cells and the understanding of their regulatory role in the immune response.

PMID- 8535151
TI  - Purification and activity of a wheat 9-kDa lipid transfer protein expressed in
      Escherichia coli as a fusion with the maltose binding protein.
AB  - The cDNA encoding a wheat (Triticum durum) lipid transfer protein of 9 kDa was
      inserted into an Escherichia coli expression vector, pIH902, and expressed in the
      bacteria as a fusion with the maltose binding protein. The fusion protein was
      then purified to homogeneity and subjected to factor Xa cleavage. Although
      complete cleavage of the fusion protein was obtained, the expected lipid transfer
      protein was not recovered; it appears to be degraded during protease digestion.
      However, a fluorescent lipid transfer assay demonstrated that the fusion protein
      has an activity identical to that of the wheat-purified lipid transfer protein.
      Thus, this expression system should allow further understanding of the
      structure/function relationships of wheat lipid transfer proteins.

PMID- 8535152
TI  - Purification, functional characterization, and crystallization of the ligand
      binding domain of the retinoid X receptor.
AB  - The ligand binding domain (LBD) of the human retinoid X receptor alpha (hRXR
      alpha) was overproduced in Escherichia coli and purified to more than 95% purity
      and functional homogeneity. Circular dichroism spectra of the purified RXR alpha
      LBD indicated that the protein was composed predominantly of alpha-helical
      structures and coils. Crystals were grown from ammonium citrate using the vapor
      diffusion method against a reservoir containing 100 mM Pipes (pH 7.0) and 1.5 M
      ammonium citrate. They belong to the hexagonal space group P6(3)22 with unit cell
      parameters a = b = 110.8 A and c = 109.9 A, alpha = beta = 90 degrees, gamma =
      120 degrees, and they diffract X rays to a resolution limit of 2.5 A using
      synchrotron radiation. The asymmetric unit of the crystals contains one molecule
      with a solvent content of approximately 55% and a Vm value of 3.6 A3/dalton.

PMID- 8535153
TI  - Purification of recombinant human rhinovirus 14 3C protease expressed in
      Escherichia coli.
AB  - A gene encoding the human rhinovirus 14 (HRV14) sequence for expression of the
      viral polypeptide protein delta 3ABC was inserted into a plasmid driven by the
      heat-inducible bacteriophage lambda PL promoter. The coding sequence was also
      inserted into a pET vector for expression in the T7 system to produce 13C, 15N
      labeled protein. The expressed HRV14 3C protease (3Cpro) autocatalytically
      cleaved itself from the polyprotein delta 3ABC, and the mature HRV14 3Cpro
      partitioned predominantly, in the case of the T7 system, in the insoluble
      fraction and exclusively, in the case of the PL system, in the insoluble
      fraction. The insoluble HRV14 3Cpro was solubilized in urea and purified using
      anion- and cation-exchange chromatography. The protease was refolded/activated
      and further purified using a size-exclusion column. HRV14 3Cpro was purified to >
      90% homogeneity as shown by SDS-PAGE and to 95% by HPLC. A continuous
      fluorescence assay was developed which utilized an intramolecularly quenched 9
      amino-acid substrate. The substrate anthranilic acid (Anc)-Thr-Leu-Phe-Gln-Gly
      Pro-Val-(p-NO2)-Phe-Lys mimicked the natural 2C/3A cleavage site (Thr-Leu-Phe-Gln
      Gly-Pro-Val-Tyr-Phe) using an N-terminal anthranilic acid donor group on one side
      of the scissile bond (Gln/Gly) and a p-NO2-Phe acceptor group at the P4 position.
      Measured by the fluorescence assay, HRV14 3Cpro had a Km of 300 microM for the
      substrate.

PMID- 8535154
TI  - Production and purification of N-terminal half-transferrin in Pichia pastoris.
AB  - Human serum transferrin, the major iron transport protein in humans, is a
      monomeric glycoprotein that is composed of two homologous domains; the N-terminal
      domain is formed by amino acids 1-331 and the C-terminal domain is formed by
      amino acids 338-679. Each domain is capable of binding one iron atom
      concomittantly with a carbonate anion; however, the two homologous iron binding
      sites are not chemically equivalent. The cDNA sequence coding for the N-terminal
      domain has been cloned and overexpressed in the methylotrophic yeast, Pichia
      pastoris. The transformants secrete a protein of approximately 38 kDa (the size
      expected for N-terminal half-transferrin), its N-terminal sequence agrees with
      the predicted sequence, and the protein reacts with anti-human serum transferrin
      antibodies. The purified protein appears to be properly folded and can bind iron
      as demonstrated by its spectral properties and urea-PAGE mobility. It is
      estimated that N-terminal half-transferrin represents approximately 90% of all
      protein secreted into the culture medium and that it is expressed at levels
      exceeding 50 mg/l. This study demonstrates that N-terminal half-transferrin can
      easily be expressed in the simple host system, Pichia pastoris, and that the
      purified protein is capable of reversibly binding iron.

PMID- 8535155
TI  - Expression and functional characterization of Escherichia coli NusA and lambda Q
      as glutathione S-transferase fusion proteins.
AB  - The Escherichia coli transcription factor NusA and the bacteriophage lambda
      antiterminator Q proteins were expressed as inducible glutathione S-transferase
      (GST) fusion proteins. The fusion proteins were purified under nondenaturing
      conditions by affinity chromatography on glutathione agarose. Thrombin cleavage
      of the glutathione agarose-bound fusion proteins yielded homogeneously pure
      NusAN+15 (5 mg/g cells) and almost homogeneously pure QN+13 protein (0.7 mg/g
      cells), where N+x indicates the presence of x additional amino acids at the N
      terminus of the protein. The purified NusAN+15 exhibited the same activities as
      wildtype NusA in enhancement of transcriptional pausing, enhancement of
      termination at Rho-independent terminators, and enhancement of Q-mediated
      antitermination in vitro. The QN+13 protein exhibited both anti-pausing and
      antitermination activities in Q-mediated transcription antitermination. However,
      the antitermination activity of QN+13 was lost gradually during storage if the
      thrombin used for cleavage of the GST fusion protein was not removed. This was
      due to cleavage by thrombin after Arg22 within the Q protein itself, at a
      noncanonical thrombin cleavage site, so the truncated protein (QN+22) lacked the
      first 22 amino acids at the N-terminus of Q. The expression vectors described
      here can be used to rapidly produce large quantities of these proteins, and the
      truncated Q protein can be used to evaluate the requirement for the N-terminus of
      Q in antitermination, anti-pausing, interactions with the DNA template (qut
      site), and interaction with RNA polymerase itself.

PMID- 8535156
TI  - Purification of a maize dehydrin protein expressed in Escherichia coli.
AB  - A maize dehydrin protein (Dhn1) containing 167 amino acids with a predicted
      molecular weight of 17.0 kDa was produced in the Escherichia coli overexpression
      strain BL21 (DE3)pLysS. Site-directed mutagenesis was used to construct a plasmid
      with a protein coding region corresponding exactly to the original cDNA. Protein
      production was induced by IPTG. Dhn1 was enriched from total soluble protein by
      heat-fractionation and centrifugation and then purified by sequential cation
      exchange and hydrophobic interaction chromatography. The purified protein was
      visualized by SDS-PAGE and immunoblot analysis using a polyclonal antibody to the
      dehydrin consensus region. Expression in E. coli resulted in approximately 1.2 mg
      of purified protein per liter of induced culture.

PMID- 8535157
TI  - Overexpression and purification of Thermus thermophilus elongation factors G, Tu,
      and Ts from Escherichia coli.
AB  - The translation elongation factors G (EF-G), Tu (EF-Tu), and Ts (EF-Ts) from the
      extreme thermophilic bacterium Thermus thermophilus were overproduced in
      Escherichia coli. The fus gene coding for EF-G and the tufA gene coding for EF-Tu
      were expressed under the control of a tac promoter, whereas EF-Ts was
      overproduced with the T7 RNA polymerase system. A detailed description for the
      purification of the three elongation factors from E. coli is presented. EF-G and
      EF-Tu are isolated by Q-Sepharose FF chromatography, heat treatment at 65 or 60
      degrees C, respectively, and Sephacryl S200 gel permeation chromatography. For
      the purification of EF-Ts, a heat denaturation step is followed by DEAE-cellulose
      chromatography and a cation exchange EMD-SO-3 650 column. The overproduced
      factors show the same properties as those purified from T. thermophilus. As the
      crystal structures of T. thermophilus EF-Tu and EF-G have been solved recently,
      many questions concerning the function of particular residues or domains arise,
      which may be best addressed by studying the in vitro behavior and structure of
      altered recombinant constructs. The methods presented here should facilitate such
      studies.

PMID- 8535158
TI  - Lactose fed-batch overexpression of recombinant metalloproteins in Escherichia
      coli BL21 (DE3): process control yielding high levels of metal-incorporated,
      soluble protein.
AB  - A method for producing recombinant proteins in pilot scale fermentation equipment
      using a glucose fed-batch initial growth, followed by a midlog phase feeding of a
      glucose and lactose mixture is described. Using the host strain Escherichia coli
      BL21(DE3), the diiron protein stearoyl-acyl carrier protein delta 9 desaturase
      has been overexpressed at a biomass level of up to 12 g x liter-1 dry cell
      weight, representing a 12-fold increase in volumetric productivity relative to
      that obtained from batch fermentations. Under these conditions, a maximum of 36%
      of the total cellular protein accumulates as the desaturase polypeptide. A
      correlation between the slowed growth rate of the fed-batch culture, a continued,
      albeit slower, exponential growth under inducing conditions, and a favorable
      partitioning between formation of the soluble holoprotein and inclusion bodies is
      reported. This correlation suggests that fed-batch techniques can be used to
      beneficially influence rate-limiting processes in the maturation of overexpressed
      proteins, such as metal uptake and incorporation proposed here. By using cells
      produced from the fed-batch method, the iron-containing, soluble desaturase can
      be purified in a yield of up to 66 mg x g-1 dry cell weight (approximately 500 mg
      x liter-1 culture), representing a three to fivefold increase in the yield
      relative to that obtained from batch fermentations. In addition, these methods
      are suitable for the production of the Anabena 7120 vegetative [2Fe 2S]
      ferredoxin in E. coli BL21(DE3) pLysS, a host strain used for the overexpression
      of toxic proteins.

PMID- 8535159
TI  - Reconstitution of active human calcineurin from recombinant subunits expressed in
      bacteria.
AB  - Calcineurin, a protein phosphatase found in eukaryotic cells, presents a
      challenging problem in heterologous protein expression because it is both
      heterodimeric and posttranslationally modified. In this paper, we describe the
      cloning of both subunits (catalytic A and regulatory B) of calcineurin from a
      human cDNA library and their expression at high levels in Escherichia coli. The
      calcineurin A subunit is expressed as an insoluble glutathione S-transferase
      fusion protein, while the calcineurin B subunit is soluble upon direct
      expression. Catalytically active holoenzyme is derived from the separately
      expressed subunits using a three-step refolding protocol. First, the fusion
      protein is solubilized, then it is cleaved at the fusion junction with thrombin,
      and, finally, a catalytically competent calcineurin A:calcineurin B:calmodulin
      complex is reconstituted by cofolding the separately purified components. In
      addition, we show that a similar refolding protocol can be applied to a C
      terminally truncated form of calcineurin A, which lacks an autoinhibitory and
      calmodulin-binding domain.

PMID- 8535160
TI  - Catalytic and cytotoxic activities of recombinant ricin A chain mutants with
      charged residues added at the carboxyl terminus.
AB  - Ricin A chain (RTA) mutants which had been modified by the addition of three
      lysine residues, three lysines and an alanine, or six histidine residues at the
      carboxyl terminus were expressed in Escherichia coli. The recombinant proteins
      were purified to homogeneity by ion-exchange chromatography on CM-Sepharose CL
      6B. The 28S ribosomal RNA N-glycosidase activities of the three RTA mutants were
      indistinguishable from each other and from the activity of wild-type recombinant
      RTA. The RTA mutants were not impaired, compared with wild-type RTA, in their
      ability to reassociate with ricin B chain to form ricin holotoxin. Holotoxins
      containing mutant RTAs were as readily dissociated into subunits under reducing
      conditions as native holotoxin, and the RTA mutants were indistinguishable from
      wild-type RTA in the extent of their interaction with biological membranes. Ricin
      holotoxins containing the RTA mutants were, however, less cytotoxic to Vero cells
      than ricin containing wild-type RTA. At equivalent concentrations, a time course
      assay showed that holotoxin containing the mutant RTAs took longer to kill target
      cells than that containing wild-type recombinant RTA, suggesting that the mutant
      forms of RTA are less efficiently processed or translocated across an
      intracellular membrane than is wild-type RTA.

PMID- 8535161
TI  - High-yield expression, refolding, and purification of penicillin-binding protein
      2a from methicillin-resistant Staphylococcus aureus strain 27R.
AB  - The mecA-27R gene, which encodes PBP2a from methicillin-resistant Staphylococcus
      aureus strain 27R, was modified to remove the putative N-terminal membrane
      spanning region, cloned into the T7 RNA polymerase expression vector pET11d, and
      used to transform Escherichia coli strain BL21(DE3). The majority of PBP2a was
      expressed in the form of inclusion bodies, which were extracted, denatured, and
      refolded. The protein was then purified by anion-exchange and size-exclusion
      chromatography. A 6-liter culture of induced E. coli provided 37 mg of purified
      PBP2a which was greater than 99% pure. Binding affinities for
      [3H]benzylpenicillin, imipenem, and L-695,256 (a beta-lactam with high affinity
      for PBP2a) were shown to be comparable to PBP2a found in membrane preparations of
      S. aureus strain 27R. A direct binding assay, using 14C-labeled L-695,256 was
      developed and used to show stoichiometric binding to the refolded, soluble PBP2a.
      In addition, electrospray mass spectrometry showed that 100% of the refolded
      PBP2a was covalently bound to the beta-lactam in a stoichiometric fashion.
      Finally, two mutations of the putative active-site serine showed the predicted
      loss of covalent binding of the beta-lactam to the PBP2a, demonstrating the high
      specificity of the soluble binding assay.

PMID- 8535162
TI  - Overexpression and purification of the trimeric aspartate transcarbamoylase from
      Bacillus subtilis.
AB  - A procedure has been developed for the overexpression and purification of
      milligram quantities of the Bacillus subtilis aspartate transcarbamoylase. The
      plasmid pEK171, carrying the B. subtilis pyrB structural gene under the control
      of the Escherichia coli pyrBI promoter, was transformed into the E. coli strain
      EK1104 and the enzyme overexpressed to approximately 50% of total soluble protein
      under extreme derepression of the pyrimidine pathway. The enzyme was subsequently
      purified by means of ammonium sulfate fractionation, anionic exchange
      chromatography using Q-Sepharose Fast Flow resin, negative chromatography on
      Matrex Gel Red A agarose, and hydrophobic interaction chromatography using Matrex
      Phenyl Cellufine. The purification yields approximately 60 mg of pure enzyme per
      liter of bacterial culture. Kinetic analysis of the overexpressed enzyme
      indicated that it had kinetic properties very similar to those of the enzyme
      purified from B. subtilis cells.

PMID- 8535163
TI  - Expression in Escherichia coli and purification of human eosinophil-derived
      neurotoxin with ribonuclease activity.
AB  - Eosinophil-derived neurotoxin (EDN) is a ribonuclease with neurotoxic and
      helminthotoxic properties. It is present in the crystalloid granules of human
      eosinophils. We report the expression and characterization of a functionally
      active recombinant human EDN using the pMAL-cRI expression system. A cDNA for
      mature EDN was obtained by PCR and inserted in pMAL-cRI downstream of the malE
      gene encoding maltose binding protein. Induction of the ptac promoter of the
      plasmid in Escherichia coli strain BL21(DE3) resulted in high level expression of
      soluble MAL-EDN fusion protein. Cleavage of affinity purified fusion protein with
      Factor Xa protease released recombinant EDN which comigrated with native EDN on
      SDS-polyacrylamide gels and cross-reacted with a polyclonal anti-EDN antiserum on
      Western blots. IN contrast to previous attempts at EDN expression, denatured and
      refolded EDN had ribonuclease activity and was prepared in microgram amounts. The
      availability of recombinant human EDN should facilitate studies of its structure
      and biological functions.

PMID- 8535164
TI  - Chinese hamster rhodanese cDNA: activity of the expressed protein is not blocked
      by a C-terminal extension.
AB  - We describe a cDNA from Chinese hamster ovary cells which encodes a protein 91
      and 96% identical to bovine and rat mitochondrial rhodaneses, respectively.
      Recombinant protein was expressed from the cDNA in Escherichia coli, purified to
      homogeneity, and found to have kinetic properties nearly indistinguishable from
      those of the bovine enzyme, the only cloned rhodanese previously verified by
      characterization of the recombinant protein. The carboxyl-terminus of the enzyme
      is characterized by a duplicated tripeptide, which can be proteolytically
      processed in vivo. We constructed a mutant in which the last 5 amino acids were
      replaced by 28 residues of unrelated sequence. This protein was expressed,
      purified, and found to have kinetic constants similar to those of the wild-type
      enzyme. The functionally verified Chinese hamster rhodanese cDNA encodes a
      protein of 297 residues and differs from the rat enzyme at 13 positions. None of
      these substitutions occurs at residues suggested to play essential roles in
      catalysis or structural stabilization.

PMID- 8535166
TI  - High yield purification of a four subunit caa3-type cytochrome oxidase from the
      thermophilic bacterium Bacillus PS3 using fast protein liquid chromatography.
AB  - The thermophilic bacterium, Bacillus PS3, was grown in a vigorously aerated
      nutrient broth at 65 degrees C with 100 mM glutamic acid serving as a
      supplemental carbon and nitrogen source. These growth conditions resulted in
      membranes highly enriched in cytochrome c oxidase (COX) [23.32 +/- 4.32 nmol heme
      a/g of cells (n = 5)], which is nearly a threefold higher concentration of COX
      (heme caa3-type) than previously reported for this organism. A new high-yield
      purification of COX was performed by extracting the bacterial membranes with
      Triton X-100 (7 mg/mg protein), followed by ion-exchange fast liquid protein
      chromatography using a QAE (trimethyl ammonium) resin with subsequent
      hydroxyapatite chromatography and ammonium sulfate fractionation. This
      purification regime resulted in a 16% yield of cytochrome c oxidase with 20 mg of
      pure caa3-type COX (13 nmol heme a/mg protein) isolated from 100 g of cells. SDS
      PAGE showed that the isolated enzyme had four subunits with apparent Mr of 68,
      38, 23, and 13 kDa. In addition, a new 34-kDa peptide was also detected in this
      preparation, which may represent the ORF1 gene product for this organism. Subunit
      II (Mr = 38 kDa) of the isolated enzyme was shown to contain covalently bound
      heme c by using both heme-staining of SDS-PAGE and immunoreactivity with an anti
      cytochrome c antibody. The purified enzyme also exhibited high electron transfer
      activity (340s-1) when assayed at pH 6.5 in the presence of the nonionic
      detergent, beta-dodecyl maltoside.

PMID- 8535165
TI  - Production of rat protein disulfide isomerase in Saccharomyces cerevisiae.
AB  - Protein disulfide isomerase (PDI) is an abundant protein of the endoplasmic
      reticulum that catalyzes the oxidation of protein sulfhydryl groups and the
      isomerization and reduction of protein disulfide bonds. Saccharomyces cerevisiae
      cells lacking PDI are inviable. PDI is a component of many different protein
      processing complexes, and the actual activity of PDI that is required for cell
      viability is unclear. A cDNA that codes for rat PDI fused to the alpha-factor pre
      pro segment was expressed in a protease-deficient strain of S. cerevisiae under
      the control of an ADH2-GAPDH hybrid promoter. The cells processed the resulting
      protein and secreted it into the medium as a monomer, despite having a KDEL or
      HDEL sequence at its C-terminus. The typical yield of isolated protein was 2 mg
      per liter of culture. The catalytic activity of the PDI from S. cerevisiae was
      indistinguishable from that of PDI isolated from bovine liver. This expression
      system is unique in allowing the same plasmid to be used both to complement pdi1
      delta S. cerevisiae and to produce PDI for detailed in vitro analyses.
      Correlations of the in vivo behavior and in vitro properties of PDI are likely to
      reveal structure-function relationships of biological importance.

PMID- 8535167
TI  - About copyright and copywrong.

PMID- 8535168
TI  - The impairment of mitochondrial membrane potential and mass in proliferating
      lymphocytes from vitamin E deficient animals is recovered by glutathione.
AB  - The time-dependent changes of mitochondrial membrane potential and mass have been
      investigated on splenocytes from control and vit. E deficient rats, stimulated to
      proliferate with Concanavalin A, in the presence and absence of reduced
      glutathione (GSH, 5 mM). Rhodamine-123 (Rh-123) and nonyl acridine orange (NAO)
      were used as specific probes to monitor the membrane potential and mass of
      mitochondria, respectively, by means of flow cytometry. Rh-123 uptake was high in
      an increasing number of cells from normally fed animals during the three-day
      culture period. On the contrary, splenocytes from vitamin E deficient rats showed
      a biphasic pattern. The number of cells showing a high uptake of Rh-123 increased
      after 24 hrs. from mitogenic stimulation, then it decreased at the other two time
      points considered. In parallel, a continuous increase of the number of cells with
      depolarized organelles (up to 60% by 72 hrs.) has been observed in vit. E
      deficiency. This impairment was fully prevented by GSH supplementation to the
      culture medium. In the presence of the thiol, about 80-85% of cells showed
      activated mitochondria, whereas the number of splenocytes with depolarized
      organelles did not exceed 17%, irrespective of the diet applied to the animals.
      The same pattern was observed considering the changes of mitochondrial mass,
      measured using NAO as a probe. Present results support that GSH may substitute
      vitamin E in protecting mitochondria from peroxidative damage.

PMID- 8535169
TI  - The correlative evidence suggesting that trehalose stabilizes membrane structure
      in the yeast Saccharomyces cerevisiae.
AB  - The contribution of trehalose and hsp104 to membrane fluidity and the mobility of
      non-freezing cell water were examined on the basis of whole cell NMR analysis of
      the yeast Saccharomyces cerevisiae. Membrane fluidity was dependent on the
      accumulation of trehalose not hsp104 and non-freezing cell water was dependent on
      the accumulation of hsp104 not trehalose. Thus, the correlative evidence
      suggesting that trehalose protects yeast cells from temperature extremes by
      stabilizing the membrane structure was observed in vivo.

PMID- 8535170
TI  - Inhibition and down-regulation of poly(ADP-ribose) polymerase results in a marked
      resistance of HL-60 cells to various apoptosis-inducers.
AB  - In a previous report we described that adenosine-induced apoptosis of HL-60 cells
      was blocked by the pretreatment of cells with a potent inhibitor (3
      aminobenzamide) of poly(ADP-ribose) polymerase (PARP). The pretreatment of the
      cells with nicotinamide, another inhibitor of the enzyme, also suppressed most
      effectively the adenosine-induced apoptosis. This inhibition was reversible and
      observed during apoptosis mediated by other known apoptosis inducers such as
      actinomycin D and staurosporine (group I inducers), but nicotinamide was
      ineffective on the apoptosis mediated by VM 26, camptothecin and A23187 (group II
      inhibitors). In addition to the enzyme inhibition, a down-regulation of the
      enzyme level caused by the pretreatments of cells with differentiation-inducing
      agents, retinoic acid (RA) and dimethylsulfoxide (DMSO) also resulted in a marked
      resistance of the cells to the apoptosis inducers. A pretreatment of the cells
      for a limited time of 24 hrs. by these agents decreased the PARP level to 66-75%
      of the untreated cells and the cells showed a quite similar resistance to the
      group I apoptosis inducers like the cells treated with the enzyme inhibitors,
      whereas they were still sensitive to the group II inhibitors. A more prolonged
      treatment for 48 hrs. of the cells with RA and DMSO resulted in further down
      regulation of the cellular PARP reaching respectively 50 and 43% of control cells
      and at this stage, the cells became resistant to all the inducers of both groups.
      These results suggest that the pathway, by which both groups of the inducers
      initiate and progress apoptosis, is not identical but include at least two
      different processes which are differently affected by PARP-inhibition or by
      different levels of cellular PARP.

PMID- 8535171
TI  - Three dimensional observation of whole mount cultured cells stained with
      histochemical reactions by ultrahigh voltage electron microscopy.
AB  - Thick biological specimens prepared as whole mount cultured cells stained with
      histochemical reactions, such as thiamine pyrophosphatase, glucose-6-phosphatase,
      cytochrome oxidase, acid phosphatase, DAB reactions demonstrating specific cell
      organelles such as Golgi apparatus, endoplasmic reticulum, mitochondria,
      lysosomes, peroxisomes and pinocytotic vesicles, were observed by ultrahigh
      voltage electron microscopy at accelerating voltages of 400-1000 kV producing
      stereo-pairs. As a result, those cell organelles were observed 3-dimensionally
      and the relative relationships between these organelles demonstrated.

PMID- 8535172
TI  - c-fos mRNA is present in axons of the hypothalamo-neurohypophysial system of the
      rat.
AB  - In situ hybridization revealed that c-fos encoding transcripts occur in the
      median eminence of rats. Osmotic stress resulted within 15 min. in additional
      labeling of the magnocellular nuclei, while osmotically stimulated rats that had
      been pretreated with colchicine failed to show c-fos hybridization in the
      magnocellular perikarya. Rats, pretreated with a polymerase II inhibitor, showed
      15 min. after osmotic stimulation c-fos hybridization in the hypothalamic nuclei,
      whereas the median eminence was depleted of hybridization signal. c-fos is
      probably among the transcripts, stored in axons of the hypothalamo
      neurohypophysial system, to be transported retrogradly upon osmotic stimulation.

PMID- 8535173
TI  - Immunohistochemical evidence for sympathetic denervation and reinnervation after
      necrotic injury in rat myocardium.
AB  - To study the short and long term effects of myocardial injury on sympathetic
      nerve fibers, a necrotizing lesion was performed on the diaphragmatic side of rat
      myocardium by freeze-thawing. Animals were sacrificed at 2, 6, 18, 28 and 105
      days after the surgical procedure and paraffin-embedded hearts were subjected to
      peroxidase immunohistochemistry. According to previous studies cardiac nerves
      were visualized by staining their surrounding Schwann cells with an anti-S100
      protein antibody. Catecholaminergic axons were specifically identified by an anti
      tyrosine hydroxylase antibody. No S-100 positive structures were found in 2-day
      lesions (denervation). Starting from day 6,S-100 positive structures became
      progressively more evident (reinnervation) and persisted up to day 105. Many of
      these newly formed nerve fibers were positive for tyrosine hydroxylase,
      indicating that a necrotic injury of rat myocardium causes a disappearance of
      sympathetic innervation which is followed by a phase of sympathetic
      reinnervation.

PMID- 8535174
TI  - Effect of lactic acid on water content and osmotic fragility of erythrocytes in
      vitro.
AB  - Effects of lactic acid in red blood cells on osmotic fragility and water content
      of erythrocytes after hyperthermia were investigated. The osmotic fragility of
      erythrocytes increased following one-hour incubation with the addition of lactic
      acid at both 37 degrees C and 42 degrees C and that also increased after heating
      in vitro at 42 degrees C compared with those incubated at 37 degrees C, whether
      the lactic acid was added or not. The water content increased with the addition
      of lactic acid after heating in vitro at 42 degrees C. A high concentration of
      lactic acid and hyperthermia seem to cause the increase of intracellular water
      and the decrease of osmotic resistance of the red blood cells.

PMID- 8535175
TI  - Expression of atrial natriuretic peptide in cultured adult cardiac ventricular
      muscle cells as studied by immunofluorescence microscopy.
AB  - Atrial natriuretic peptide (ANP) is known to be present predominantly in the
      granules of adult cardiac atrial muscle cells. The functional role of this
      peptide is known to be involved in diuresis, natriuresis and control of blood
      pressure. The present study using antibody to ANP, revealed that the cultured
      adult cardiac ventricular muscle cells, unlike their counterparts in vivo,
      expressed ANP to be as abundant as in adult atrial cells. Cultured atrial cells
      did not express ANP any more than their counterparts in vivo. Both cells,
      specifically ventricular cells, contained various forms of ANP such as granular,
      aggregate, ring-shape, fibrous and amorphous in different parts of the cell body.
      Vesicular or granular ANP was also observed beneath the cell membrane, above the
      cell membrane or outside the cell body, which were possibly suggestive of
      exocytosis of ANP by cells. The current studies were extended to the cultured
      embryonic ventricular and atrial cardiac myocytes, and revealed that these cells
      expressed considerable ANP, which were comparable to those in in vivo cells,
      reported by others. The high expression of ANP in cultured adult ventricular
      cardiac muscle cells indicates that these adult cells are capable of producing
      high content of ANP as observed in embryonic ventricular cells.

PMID- 8535176
TI  - Unusual presence and intranuclear storage of silica crystals in the freshwater
      sponges Ephydatia muelleri and Spongilla lacustris (Porifera: Spongillidae).
AB  - Crystal structures have been identified in nuclei of cells from the freshwater
      sponges Ephydatia muelleri and Spongilla lacustris. Their length is approximately
      5 microns and their diameter varies from 0.8 to 1 micron. They occur in several
      different cell types, among them pinacocytes, cystencytes (E. muelleri) and
      granulocytes as well as differentiating archaeocytes (S. lacustris). In contrast
      to earlier reports it is now shown that the crystals are geometrically periodic
      and anisotropic structures composed of silica. We assume that the crystals play a
      functional role during differentiation of the cells.

PMID- 8535177
TI  - Band 3, the anion transporter, is conserved during evolution: implications for
      aging and vertebrate evolution.
AB  - A cDNA fragment corresponding to a highly evolutionarily conserved region of the
      major anion transport protein band 3 was cloned from lamprey mRNA using PCR
      homology probing. This is the first report providing evidence for a band-3 like
      transporter in the lowest vertebrates, the agnathostomes. Semi-quantitative PCR
      showed expression similar to that of higher vertebrates. Lamprey serum contains
      antibody-like molecules that bind to synthetic peptides of band 3 comprising
      senescent cell antigen, an aging antigen that terminates the life of cells. The
      high degree of homology found in nucleic acid and derived proteins sequence and
      the reaction of "antibodies" in lamprey serum with senescent cell antigen
      peptides of band 3 suggests that lamprey band 3 plays a role comparable to that
      in higher vertebrates.

PMID- 8535178
TI  - GABA uptake in a Saccharomyces cerevisiae strain.
AB  - The aim of this work was to characterize the 4-aminobutyric acid (GABA) transport
      in the Saccharomyces cerevisiae D27 strain, followed by the study of the
      relationship between 5-aminolevulinic acid (ALA) and GABA transport systems. It
      was found that the general amino acid permease (GAP) is not active in D27 strain,
      suggesting that GABA incorporation should be mediated by PUT4 and UGA4 permeases.
      However, after kinetic studies only one system was detected. It was also shown
      that GABA uptake is competitively inhibited by ALA. GABA incorporation is
      regulated by the carbon source but not by the nitrogen source. When cells were
      grown in the presence of GABA, its entrance was very low.

PMID- 8535179
TI  - Study on the DNA synthesis of pulmonary cells in aging mice by light microscopic
      radioautography.
AB  - The DNA synthesis and morphological changes of the pulmonary cells of 11 groups
      of mice from fetal day 16 to 22 months after birth were studied by light
      microscopic radioautography after 3H-thymidine incorporation. A detailed
      investigation was first carried out to determine the localization and the
      frequency of 3H-thymidine incorporation with the age-related change of pulmonary
      cells in the mouse lung. The results showed that the DNA synthesis of pulmonary
      cells changed with aging. The examination of radioautograms demonstrated that the
      activity of DNA synthesis of type 1 epithelial cells was very low, which reached
      the peak on the third day after birth, decreased gradually with aging, and lost
      the ability from postnatal 6 months onwards. On the other hand, the labeling
      indices of type 2 epithelial, interstitial and endothelial cells were the highest
      on the fetal day 16, then fell down with the developing of the lung, but
      increased again on the third postnatal day, and decreased gradually with age.
      These data provided the evidence that the DNA synthesis of type 2 epithelial,
      interstitial and endothelial cells were the largest on fetal day 16, then
      decreased with the developing of the lung due to aging.

PMID- 8535180
TI  - Spermine action on mitochondrial H(+)-ATPase activity and proliferation rate of
      Trypanosoma cruzi.
AB  - Activity of H(+)-ATPase of Trypanosoma cruzi (RA strain) submitochondrial
      particles is increased in parasites which have a low spermine content caused by
      growing in a polyamine free medium or in a medium containing inhibitors of
      polyamine synthesis. Under these conditions, the proliferation rate is markedly
      decreased. Kinetics of the enzyme inhibition by spermine indicates a non
      competitive inhibition. Spermine, through its action on the H(+)-ATPase
      hydrophobic environment, affects the enzyme activity. Together with the ATPase
      protein inhibitor, this could be a mechanism regulating ATP levels needed for the
      parasite proliferation.

PMID- 8535181
TI  - Light and electron microscopical demonstration of the ouabain-sensitive,
      potassium-dependent p-nitrophenylphosphatase activity (K-NPPase) using a Ce-Mg
      double capture technique.
AB  - The cerium-based method of Kobayashi et al. for the histochemical demonstration
      of K-NPPase activity was improved. Besides Ce3+ additionally Mg2+ ions as
      orthophosphate capture were employed (double capture technique). For light
      microscopical purposes the Mg-phosphate was converted into Ce-phosphate by
      treatment of the sections with Ce-citrate yielding higher quantity of reaction
      product. Unspecific background staining was eliminated by EGTA. In the electron
      microscope this technique brought about fine granular reaction products without
      diffusion artefacts.

PMID- 8535182
TI  - Immunotoxins for treatment of leukemia and lymphoma.
AB  - Less than fifteen years have passed since the practical applications of antibody
      directed cell targeting were conceived in the laboratory. In vitro and in vivo
      applications for immunotoxins are being developed in a variety of protocols to
      treat human cancer. Immunotoxins may be particularly well-suited for the
      treatment of hematological cancers where malignant cells are more accessible than
      in solid tumors. Experimental results and clinical responses have provided
      encouragement, especially in light of the complexities of cancer biology, while
      the problems do not appear insurmountable. Continued basic research in cell
      biology combined with advances in manufacturing techniques will undoubtedly
      propose improvements in immunotoxins as well as new applications.

PMID- 8535183
TI  - Regulation of cell-matrix adhesion by receptor tyrosine kinases.
AB  - Cell-cell and cell-matrix adhesive interactions mediated by integrins play
      crucial roles in leukocyte migration to inflamed tissues, and also in cell
      migration during embryogenesis. Much remains to be learned about the molecular
      mechanisms of regulation of adhesion mediated by integrins. Recently we found
      that steel factor and c-kit induce adhesion to fibronectin by VLA-5 in mast
      cells. Activation of adhesiveness is transient, and occurs at concentrations of
      steel factor 100-fold lower than required for growth stimulation. This suggests
      that regulation of adhesion is an important biological function of steel factor
      and c-kit. Other receptor tyrosine kinases such as the PDGF receptor can
      substitute for c-kit. Signaling through receptor tyrosine kinases may offer a
      general mechanism for the regulation of integrin avidity.

PMID- 8535184
TI  - Prothymosin alpha: in search of a function.
AB  - Prothymosin alpha is an acidic nuclear protein that is expressed at high levels
      in a wide variety of cell types. Accumulating data correlate prothymosin
      expression with alterations in the proliferative state of cells. Some data
      indicates that prothymosin may actually be necessary, if not sufficient, for
      proliferation, and that prothymosin may function in a c-myc associated pathway.
      Prothymosin is highly conserved through evolution suggesting a key function,
      however, that function remains unknown.

PMID- 8535185
TI  - Interferon-gamma in multiple myeloma.
AB  - Biological heterogeneity is a characteristic of multiple myeloma. A dysregulated
      cytokine network underlies the various phases of the disease. Numerous cytokines,
      either promoting or inhibiting plasma cell growth, are involved in tumor control.
      Interferon-gamma (IFN-gamma) showed the most powerful inhibiting activity on
      myeloma cell proliferation. This effect was demonstrated on IL-6 dependent
      myeloma cell lines, but not on IL-6 independent ones. It was also evident on
      fresh explanted bone marrow myeloma cells. The antiproliferative effect of IFN
      gamma seems mainly due to the inhibition of IL-6, the central myeloma growth
      factor. IL-6 inhibition may occur at various levels: a downregulation of IL-6
      receptor has been reported, and also a block of the IL-6 signal transduction
      pathway via interaction with cytoplasmic proteins such as p91 has been suggested.
      Our findings showed that IFN-gamma strongly inhibited myeloma cell proliferation
      to the same extent as dexamethasone (DEX), whereas interferon-alpha (IFN-alpha)
      inhibited Ig secretion. The combined use of interferons (IFNs) showed inhibitory
      activities both on proliferation and Ig synthesis that paralleled the effects of
      DEX. In some cases, IFN-gamma was also shown to augment monoclonal immunoglobulin
      secretion suggesting a possible differentiating activity on plasma cells. The in
      vitro data encouraged pilot studies to evaluate the in vivo antitumor effects of
      IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535186
TI  - The clonogenic precursor cell in multiple myeloma.
AB  - Multiple myeloma is characterized by the monoclonal expansion of plasma cells in
      the bone marrow. Although the predominant cell type is the plasma cell, the
      initial oncogenic transformation is considered to take place in a more immature B
      cell. There is still much controversy about this precursor cell type. Phenotypic
      analysis of bone marrow and peripheral blood revealed that in multiple myeloma a
      great diversity exists in the phenotype of the cells considered to be involved.
      Because of the lack of a myeloma specific genetic lesion it is very difficult to
      trace back the cell in which the transforming event, leading to multiple myeloma,
      took place. The only real clonal marker is the idiotype of the immunoglobulin
      molecule expressed by the myeloma cells. With recombinant DNA technology it is
      now possible to produce clonal markers for each individual myeloma patient which
      recognize only the immunoglobulin genes expressed by the myeloma cell and its
      precursors. The sequences of these myeloma immunoglobulin genes do reveal a lot
      of information about the stage in the B-cell differentiation pathway in which the
      oncogenic event might have taken place. The presence of somatic mutations in a
      non-random fashion without intraclonal variation leads to the conclusion that the
      precursor myeloma cell could not possibly be a pre-B cell or stem cell but has to
      be a mature B cell that has been in contact with antigen and has past through the
      phase of somatic mutation, like a memory B cell or plasmablast.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8535187
TI  - BCR-ABL: an anti-apoptosis gene in chronic myelogenous leukemia.
AB  - The expression of bcr-abl in chronic myelogenous leukemia leads to a large
      increase in the generation of mature myeloid cells. The key biochemical
      alteration in this disease is an increased Abl kinase activity. This up
      regulation in activity is mediated through the binding of a portion of the Bcr
      molecule to the SH2 regulatory domain of the Abl protein. One effect of this
      alteration is a marked increase in resistance to drug induced cell death by
      apoptosis. This resistance can be overcome with the use of appropriate antisense
      oligonucleotides to the bcr-abl gene. The role and contribution of apoptosis to
      the development of the disease and the prospect of using antisense
      oligonucleotides as therapeutic agents is discussed.

PMID- 8535188
TI  - Platelet derived growth factor expression, myelofibrosis and chronic myelogenous
      leukemia.
AB  - CML is often associated with myelofibrosis, and fibrosis in the accelerated phase
      is one of the diagnostic criteria for this accelerated phase. In this review, the
      mechanism of myelofibrosis associated with CML is discussed with emphasis on the
      cell origin of the production and release of platelet derived growth factor
      (PDGF) and its interaction with marrow fibroblasts. In the initial stage of
      myelofibrosis in chronic phase CML, atypical small megakaryocytes might leak
      PDGF, possibly PDGF-AB, together with other growth factors. As the clinical phase
      of the disease progresses to accelerated or blastic phase, a larger quantity of
      PDGF-AB or PDGF-BB might be secreted from blastic cells with myeloid phenotype.
      In addition some fibroblasts may be attracted by the PDGF and proliferate, and
      deposit collagen as well as fibronectin in the bone marrow stroma.

PMID- 8535189
TI  - What is ineffective erythropoiesis in myelodysplastic syndromes?
AB  - The anaemia of MDS is multifactorial with intramedullary ineffective
      erythropoiesis resulting from an imbalance between erythroid proliferation,
      differentiation and apoptosis in favour of initial hypercellularity with high
      cell death through to a lower cellularity, lower death state with the eventual
      evolution of the leukaemic clone in many patients. The fundamental molecular
      abnormality(ies) in MDS, which produce the milieu for the heterogeneous molecular
      insults described (e.g., oncogene mutations) remains elusive. Many questions such
      as why MDS red cells are macrocytic and what are the precise cellular and
      molecular mechanisms of ineffective erythropoiesis remain unanswered but future
      study of the erythroid lineage should provide molecular clues to the earliest
      abnormalities in the pathogenesis of MDS.

PMID- 8535190
TI  - Induction of retinoid resistance by all-trans retinoic acid in acute
      promyelocytic leukemia after remission.
AB  - Acute promyelocytic leukemia (APL) results from a malignant process that leads to
      the accumulation in the blood and the bone marrow of myeloid precursor cells
      characterized by an abnormal behavior and a differentiation arrest. It aroused
      considerable interest well beyond the hematologic field during the last five
      years since APL has two unique features i) the remission of the disease obtained
      with all-trans retinoic acid (ATRA) treatment ii) the presence in APL blasts of
      an abnormal protein, the promyelocytic myeloid leukemia/retinoic acid receptor
      (PML/RAR alpha) protein. APL is characterized cytogenetically by a t(15;17)
      translocation which involves both the PML gene on chromosome 15 and the RAR alpha
      gene on chromosome 17 and gives rise to the PML/RAR alpha fusion protein.

PMID- 8535191
TI  - Expression of vascular cell adhesion molecule-1 by follicular dendritic cells.
AB  - Follicular dendritic cells are the major supporting cell of the germinal center
      microenvironment. The major function of follicular dendritic cells is to present
      antigen to B cells in secondary lymphoid tissues. Through cell-cell interactions,
      FDCs are hypothesized to be central to the regulation of normal B cell growth and
      differentiation. The major receptor-ligand pair which mediates B cell-FDC
      adhesion is the beta 1 integrin VLA-4, present on B cells and VCAM-1 expressed on
      FDCs. Follicular non-Hodgkin's lymphomas similarly employ this mechanism to bind
      to neoplastic germinal centers. The VCAM-1 molecule can exist as a 6 or 7
      immunoglobulin domain form. The major form of VCAM-1 on activated endothelium is
      the 7 domain form. In this report we have determined by polymerase chain reaction
      of purified FDCs that they express predominantly mRNA for 7 domain VCAM-1. It is
      likely that the two forms of VCAM-1 are associated with distinct functions,
      therefore the expression of 7 domain VCAM-1 may be important in normal and
      neoplastic B cell-FDC interactions.

PMID- 8535192
TI  - Good predictive value of combined cytogenetic and molecular follow up in chronic
      myelogenous leukemia after non T-cell depleted allogeneic bone marrow
      transplantation: a report on 38 consecutive cases.
AB  - We prospectively performed repeated cytogenetic and PCR monitoring of residual
      disease in all cases Ph positive of chronic myeloid leukemia (CML) allografted
      with non T cell depleted marrow at our institution over a period of 8 years.
      Thirty eight patients who survived the immediate post transplant period could be
      analyzed (median of 3 cytogenetic analyses/patient, examining 100 mitoses, and 4
      PCR analyses/patient). Seven of the 38 patients had a hematological relapse
      (which was extramedullary in one case) and one a purely cytogenetic relapse,
      possibly stabilised by interferon treatment. Within 6 months of transplant, Ph
      positive mitoses were seen in 2 patients, and positive PCR in most cases, without
      implying subsequent relapse. Six of the 32 patients analyzed cytogenetically more
      than 6 months post transplant had Ph positive mitoses on at least one occasion: 5
      had a hematological relapse within 7 months of positive cytogenetic analysis, and
      the remaining patient, treated by interferon remained in purely cytogenetic
      relapse. (The extramedullary relapse was not preceded by a positive marrow
      karyotype). Eight of the 38 patients had positive PCR findings on at least one
      occasion more than 6 months post transplant. Seven relapsed (6 hematological
      relapses including the extramedullary relapse, and 1 cytogenetic relapse) after 3
      to 20 months, but the remaining patient remained in CR 36 months later, with
      negative PCR. The 30 patients who never had positive PCR findings remained in CR.
      In this relatively large series of patients, we found a good correlation between
      PCR findings more than 6 months post transplant and remission or relapse
      status.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535193
TI  - A multivariate study of non Hodgkin's lymphoma involving proliferation,
      apoptosis, bcl-2 and the microenvironment.
AB  - The study was carried out on 22 patients with non-Hodgkin's lymphoma (NHL) who
      had received sequential infusions of two thymidine analogues iododeoxyuridine
      (IUdR) and bromodeoxyuridine (BrdU). Cell cycle kinetic studies seemed to
      differentiate distinctly between low grade lymphoma (n = 8, LI = 2.6%) compared
      to that of intermediate grade (n = 9, LI = 13%, p = 0.0001) and high grade NHL (n
      = 5, LI = 16.3%, p = 0.0062). While the majority of 14 intermediate and high
      grade lymphomas had a high labeling index there were 3/14 patients with a LI of
      5.5%, 5.5% and 4.1% respectively. A decrease in the rate of programmed cell death
      (PCD) or apoptosis due to the overexpression of bcl-2 has been implicated as the
      possible pathogenesis for follicular lymphoma. We determined the presence of bcl
      2 protein immunohistochemically and apoptosis by in situ end labeling of DNA
      which detects cells in early stages of PCD not recognized morphologically. Nine
      NHL patients demonstrated PCD ranging from 1%-40%, while it was undetectable in
      13/22 patients. Of these 13 cases, 6 showed the presence of bcl-2 expression. To
      understand the relationship of the microenvironment to the lymphoma cells, the
      presence of transforming growth factor beta (TGF-beta) was determined
      immunohistochemically. TGF-beta was present in all the cases where bcl-2 was
      present, except one. This study highlights some of the key biological features of
      NHL cells and their microenvironment.

PMID- 8535194
TI  - A retrospective analysis of treatment outcome in 106 cases of localized gastric
      non-Hodgkin lymphomas. Danish Lymphoma Study Group, LYFO.
AB  - 197 cases of gastric lymphoma were reported to a population-based Danish registry
      of non-Hodgkin's lymphomas. 106 of these cases were localized, representing
      stages IE and II1E, and were analyzed retrospectively, using Cox regression
      analysis. 67 had surgical resection, 51 chemotherapy, and 55 radiotherapy, or
      combinations thereof. No type of treatment showed any superiority as regards
      survival (p = 0.13). Overall 5-year survival was 67%. The pretherapeutic presence
      of fever or S-LDH-elevation had a far more significant influence on survival than
      histology or any of the treatments or treatment combinations. Surgical resection
      was associated with a significantly higher risk of late complications than
      radiotherapy, suggesting that radiotherapy may be preferable to surgery as the
      primary treatment in localized gastric lymphoma. It could not be determined from
      the available data whether the addition of chemotherapy to the primary treatment
      provides any survival benefit.

PMID- 8535195
TI  - Aggressive chemotherapy in the treatment of Burkitt's and non-Burkitt's
      undifferentiated lymphoma.
AB  - Because of the aggressive nature and frequent recurrence of malignant lymphomas
      of the undifferentiated type, we used a multi-drug induction chemotherapy regimen
      that has met with some success in children with similar type of histopathology
      followed by intensification and 8 cycles of consolidation chemotherapy in an
      attempt to prolong the duration of remission and survival in adult patients with
      this diagnosis. Fifty-one patients (median age 35 years) with undifferentiated
      malignant lymphoma were collected over a 4 year period (1984-1988) and entered
      into a phase III protocol done under the auspices of the Eastern Cooperative
      Oncology Group (ECOG). Six patients who had their diagnosis made at surgery and
      had resection of their tumor were excluded from analysis of response to therapy.
      Sixty percent of the patients had Stage IV disease. Sixteen patients had marrow
      involvement and five had central nervous system (CNS) disease. None of the
      patients received CNS radiation therapy. The 45 patients evaluated for response
      showed a response rate of 67% (30/45) and a complete response rate of 40%
      (18/45). Thirteen responders continue disease-free with a median follow-up of >
      40 months and have an estimated 5 year survival of 80%. Only two treatment
      related deaths were reported for the entire group. Patients with undifferentiated
      non-Burkitt's lymphoma had a longer survival than those with undifferentiated
      Burkitt's. We concluded that adult patients with undifferentiated lymphomas could
      be treated successfully with an aggressive multi-drug chemotherapy regimen,
      consisting of multiple alternating cycles of non-crossed-resistant chemotherapy.
      Toxicity with this aggressive prolonged regimen was acceptable.

PMID- 8535196
TI  - MDR-1 expression in non-Hodgkin's lymphomas is unrelated to treatment intensity
      or response to therapy.
AB  - Over-expression of the MDR-1 gene, which codes for P-glycoprotein, is thought to
      be an important mechanism in the drug resistance exhibited by many tumours. A
      number of chemotherapeutic agents which induce MDR-1 expression are also
      components of combination chemotherapies that are used in the treatment of high
      grade non-Hodgkin's lymphomas (NHL). We have therefore examined expression of MDR
      1 in a series of NHL by Northern blot analysis as well as investigated the
      localization of P-glycoprotein by immunohistochemistry. The series included 11
      hyperplastic reactive nodes and tonsils, 17 low grade NHL and 15 high grade NHL.
      The levels of MDR-1 mRNA were quantified by scanning densitometry and comparison
      with levels of glucose-6-phosphate dehydrogenase (G6PD). The MDR-1 mRNA was
      observed in both non-malignant and NHL tissues. Immunohistochemical staining
      revealed that expression of MDR-1 mRNA in reactive nodes was related to the
      presence of P-glycoprotein in lymphocytes, however, P-glycoprotein was apparent
      in both the reactive lymphocytes and tumour cells in the NHL samples. Elevated
      mRNA levels (2-3 fold increase) were observed in some low grade and high grade
      NHL relative to those observed in reactive lymphoid tissue. There appeared to be
      little correlation, however, between expression of the MDR-1 gene and either
      treatment intensity or response to therapy. The drug resistance that is often
      encountered in NHL patients is therefore likely to involve mechanisms other than
      over-expression of P-glycoprotein.

PMID- 8535197
TI  - Main drug-metabolizing enzyme systems in human non-Hodgkin's lymphomas sensitive
      or resistant to chemotherapy.
AB  - Non-Hodgkin's lymphomas (NHL) are one of the most chemosensitive human
      malignancies. Complete response (CR) is often achieved, but many patients relapse
      and a second CR is difficult to obtain because of the development of
      chemoresistance. In an attempt to better understand the biology and the
      chemosensitivity of these lymphoid tumors, we assessed the main drug-metabolizing
      enzyme systems in normal lymphocytes, chemosensitive NHL and chemoresistant NHL.
      Cytochromes P-450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and
      glutathione S-transferases (GST-alpha, -mu, -pi) were assayed by immunoblotting.
      UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, sulfatase, GST
      activity, and glutathione (GSH) content, were determined by spectral assays.
      Results showed the absence of all probed cytochromes P-450 in normal lymphocytes
      and NHL cells tested. GST activity was significantly lower in chemoresistant NHL
      compared to normal lymphocytes. GST-alpha was not detected in either normal
      lymphocytes or NHL cells. GST-pi was the predominant isoenzyme, and GST-mu was
      not detected in chemosensitive NHL. GSH content was significantly lower in
      chemoresistant NHL compared to other lymphoid tissues tested. The conjugating
      enzymes UDP-glucuronosyltransferase and sulfatase were similar in either
      chemoresistant NHL compared to chemosensitive NHL. The activity of the hydrolytic
      enzyme beta-glucuronidase was lower in chemoresistant compared to chemosensitive
      NHL, whereas sulfatase was higher in sensitive NHL compared to normal
      lymphocytes. Epoxide hydrolase was not detected in either normal or NHL cells
      tested. In conclusion, these studies did not show any cytochrome P-450 in human
      lymphoid cells tested, but pointed out noteworthy differences for other enzyme
      systems tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535198
TI  - Autoimmune phenomena in non-Hodgkin's lymphoma.
AB  - In order to obtain valid data on the pattern, frequency and prognostic
      significance of autoimmune derangements in non-Hodgkin's lymphoma (NHL) we
      studied 626 consecutive adult NHL patients participating in a population-based
      lymphoma registry. A total of 86 patients, corresponding to 13.7%, showed
      autoimmune phenomena (AP). Of these, 7.8% exhibited clinical autoimmune phenomena
      (CAP), and 5.9% showed immunohaematological phenomena (IHP). The distribution of
      histological subgroups of NHL in the AP and non-AP patients was similar. The same
      holds true for the CAP and IHP patients. A slight, non-significant
      overrepresentation of NHL, T-cell phenotype was found in patients with AP. CAP
      preceded the diagnosis of NHL in most patients, whereas IHP was associated with
      active lymphoma disease. AP as a whole did not predict for time to complete
      response, time to relapse or for survival. The finding that IHP patients relapsed
      earlier than CAP patients was not reflected in a significant difference in
      survival.

PMID- 8535199
TI  - Combination chemotherapy (RCM protocol: response-oriented cyclic multidrug
      protocol) for the acute or lymphoma type adult T-cell leukemia.
AB  - 43 patients with the acute or lymphoma type ATL were treated with the new
      combination chemotherapy (RCM protocol: response-oriented cyclic multidrug
      protocol) between January 1989 and December 1991. Complete response (CR) and
      partial response (PR) were achieved in 20.9% and 65.1% of all treated patients
      respectively. The median duration of survival was 6.0 months. The survival
      duration of patients with a high serum lactate dehydrogenase (LDH) value (> or =
      1,000 unit) and/or a poor performance status (PS) (PS 3 or 4) were also improved
      but not in patients with a severe leukocytosis (> or = 35,000/microliters).
      Toxicity was mild (grade 1 or 2) except hematologic toxicity in 4 patients (9.3%)
      and alopecia in one patient (2.3%). In spite of many patients with a poor PS (PS
      3 or 4), our chemotherapeutic results are equal or superior to other previous
      reports. It seems that response-oriented chemotherapy is suitable for the ATL
      patients with poor prognostic factors. These results indicate that the RCM
      protocol is very useful as the first choice chemotherapy for the acute or
      lymphoma type ATL.

PMID- 8535200
TI  - Evidence for a seasonal variation in the presentation of Hodgkins disease.
AB  - An analysis by month of diagnosis was made of 1359 cases of Hodgkins disease (HD)
      on the Scotland and Newcastle Lymphoma Group (SNLG) registry 1979-1992 to look
      for evidence of seasonality. A March peak was evident when all cases were
      analysed (p < 0.01). The histological subtypes nodular sclerosing (NS) and mixed
      cellularity (MC) showed a similar pattern (p < 0.05) while lymphocyte depleted
      (LD) and lymphocyte predominant (LP) had no demonstrable seasonal variation. In a
      breakdown by age and sex there was evidence of seasonality in both sexes but only
      under the age of 40. This provides further evidence for the heterogeneity of HD
      and supports the hypothesis that different factors are involved in the aetiology
      of this condition in younger compared to older patients.

PMID- 8535201
TI  - G-CSF stimulated donor granulocyte collections for neutropenic sepsis.
AB  - Granulocyte transfusions may be beneficial in neutropenic patients with
      progressive infections despite appropriate antibiotics. In order to evaluate both
      the feasibility of granulocyte collection in normal donors receiving granulocyte
      colony-stimulating factor (G-CSF) and the efficacy of infusing these cells into
      neutropenic patients with progressive sepsis, four donors received between 5-10
      micrograms/kg G-CSF per day and underwent leucapheresis within a day of the first
      dose. Different red cell sedimenting agents and interface settings were evaluated
      to determine the optimal method of granulocyte collection. The number of
      granulocytes collected, the peripheral blood granulocyte level in the recipient
      at various time points after infusion, and the clinical response were evaluated.
      Results showed that G-CSF and the leucaphereses caused mild to moderate fatigue
      in two donors and profound fatigue and a brief episode of hypoxia in one donor.
      Efficient granulocyte collections were only obtained using dextran 40 or dextran
      70 as the sedimenting agent and a deep interface setting which extended sampling
      into the upper red cell layer. Infusion of granulocytes obtained with this
      technique resulted in a sustained increase in circulating granulocyte numbers in
      three recipients, one of whom gained significant clinical benefit. In conclusion,
      granulocyte transfusions from donors given G-CSF are feasible and may be
      clinically beneficial, particularly if given early in the course of infection in
      neutropenic patients.

PMID- 8535202
TI  - Correlation of the site of M-bcr breakpoint with chronic phase duration, blastic
      crisis lineage and thrombocytosis in Ph1-positive chronic myelogenous leukemia.
AB  - The breakpoints on chromosome 22 in CML occur within a 5.8 kb region called the
      Major breakpoint cluster region (M-bcr). DNA mapping within the M-bcr region was
      performed in 41 long term followed Ph1-positive CML patients using the Southern
      blot technique. The purpose of this study was to determine whether localization
      of M-bcr breakpoint correlates with the length of chronic phase of the disease,
      blastic crisis lineage and thrombocytosis at the time of initial diagnosis. Our
      results fail to indicate any correlation between breakpoint localization and
      duration of chronic phase, blastic crisis lineage and platelet count at
      diagnosis.

PMID- 8535203
TI  - Ultrastructural studies of the megakaryoblastic leukemias of Down syndrome.
AB  - The ultrastructure of the leukemic cells in transient leukemia (six cases),
      myelodysplasia (five cases) and acute megakaryoblastic leukemia (one case) in
      patients with Down syndrome were studied. The cells were identified to be of
      megakaryocytic lineage by virtue of the expression of platelet glycoprotein
      GpIIIa, detected by immunogold labelling. In all patients, some of the leukemic
      cells had ultrastructural features of megakaryocytes, including ectoplasmic
      protrusions, demarcation membranes, and alpha granules. Differentiation was
      greatest in the cells of patients with transient leukemia. These studies provide
      a detailed assessment of the ultrastructural features of the leukemic cells in
      the megakaryoblastic leukemias of Down syndrome.

PMID- 8535204
TI  - Autologous bone marrow transplantation for second or greater complete remission
      of acute myeloid leukaemia and acute lymphoblastic leukaemia.
AB  - Twenty patients with acute leukaemia in second or greater complete remission have
      undergone autologous bone marrow transplantation (ABMT) in our centre. Twelve
      patients had acute myeloid leukaemia (AML) and eight patients had acute
      lymphoblastic leukaemia (ALL). Six of the patients treated for AML remain in CR.
      Of the eight patients with ALL, all have died within one year of transplantation.
      In the patients with AML there was no relationship between the duration of
      previous CR and outcome of ABMT.

PMID- 8535205
TI  - Alpha-interferon and corticosteroids as initial treatment in small cleaved-cell
      lymphoma.
AB  - Small cleaved-cell lymphoma (SCCL) is a non-Hodgkin's lymphoma of low clinical
      grade, highly responsive to radiation and cytotoxic therapy in its early stages,
      but ultimately fatal as disease progresses and becomes resistant to therapy. This
      study reports favourable results using recombinant alpha interferon (alpha IFN)
      and corticosteroids (CS) in five previously-untreated patients with advanced
      SCCL. Complete response (CR) was seen in three, excellent partial responses (PR)
      in the other two, with good patient tolerance. Some possible neurotoxicity was
      observed. As a strategy to minimise or delay cytotoxic exposure in these
      patients, it appears to have merit.

PMID- 8535206
TI  - Dual rearrangement of immunoglobulin and T-cell receptor genes in a case of
      splenic lymphoma with villous lymphocytes.
AB  - We report here a case of "splenic lymphoma with villous lymphocytes" (SLVL) which
      exhibited both B- and T-cell phenotypes and genotypes. The patient was a 73-year
      old man. Physical examination revealed splenomegaly and lymphadenopathy. The
      white blood cell count was 55.2 x 10(9)/L with 70.5% atypical lymphocytes, having
      cytoplasmic villi, characteristic of SLVL. The atypical cells infiltrated both
      the red and white pulps. Immunological analysis of the peripheral leukocytes
      showed both B- and T-cell phenotypes (CD5,CD11c,CD19,CD20,HLA-DR, SmIgM and
      lambda positive). DNA analysis revealed a dual rearrangement of the
      immunoglobulin heavy chain gene and T-cell receptor beta gene. SLVL has been
      identified as a B-cell leukemia with a relatively benign clinical course. This
      case had both B- and T-cell pheno- and genotypes with a progressive course. To
      the best of our knowledge, no case of SLVL with dual genotypes has ever been
      reported.

PMID- 8535207
TI  - T-cell acute lymphoblastic leukemia occurring in the course of B cell chronic
      lymphocytic leukemia: a case report.

PMID- 8535208
TI  - Chylous effusions in CLL.

PMID- 8535209
TI  - Poor cellular uptake of antisense oligodeoxynucleotides: an obstacle to their use
      in chronic myeloid leukaemia.
AB  - The molecular effect of the Philadelphia translocation typical of over 90% of
      chronic myeloid leukaemia (CML) patients is to create a novel hybrid gene, bcr
      abl. The mRNA transcript of this CML-specific gene has only 2 alternative
      sequences, designated b3a2 and b2a2. Short oligodeoxynucleotide (ODN) sequences
      complementary (or antisense) to the bcr-abl junction may have potential as
      leukaemia-specific therapy. However, the studies on ODN targeting bcr-abl
      reported so far have used ODN linked by either phosphodiester or
      phosphorothionate linkages. Both of these ODN structures have drawbacks as
      potential therapeutic agents (nuclease sensitivity, non-specific effects). In
      contrast, ODN linked by a mixture of methylphosphonate and conventional linkages
      can mediate cleavage of bcr-abl mRNA target in a sequence-specific fashion,
      unlike conventionally linked ODN. Poor ODN uptake into intact cells remains a
      central difficulty for all ODN structures. Several strategies to improve cellular
      uptake of ODN are under current investigation.

PMID- 8535210
TI  - Hepatocyte growth factor--pleiotropic cytokine produced by human leukemia cells.
AB  - Hepatocyte growth factor (HGF) was identified, purified and molecularly cloned as
      a potent mitogen for mature rat hepatocytes in primary culture. It is one of the
      largest cytokines and is composed of disulfide-linked subunits of approximately
      60 (heavy chain) and 35 kilodaltons (light chain). Recent observations revealed
      that HGF is mitogenic to various epithelial cells other than hepatocytes and to
      endothelial cells, and that it also acts as a motogen, morphogen and tumor
      suppressor as well as a mitogen. These various biological activities of HGF are
      presumably transduced through the same receptor, c-Met, which is a member of the
      tyrosine kinase receptor family. Although it shows multiple biological activities
      on cells in culture, HGF is most likely the physiological hepatotrophic factor
      which triggers liver regeneration. It may also function as a renotrophic and
      pulmotrophic factor after tissue injury. HGF production in the liver, kidney and
      lung increases after injury to these organs. An elevated HGF level may act as an
      inducer of compensatory DNA synthesis. The regulation of HGF production is,
      therefore, important for the control of organ regeneration. HGF is produced
      mainly by mesenchymal cells such as fibroblasts and vascular smooth muscle cells.
      Various types of human leukemia cells also secrete HGF both in vitro and in vivo.
      Some biological activities of HGF on hematopoietic cells, including co-mitogenic
      activity on myeloid leukemia cell lines, were recently demonstrated. HGF gene
      expression and the protein production in leukemia and fibroblast cells are
      modulated by various cytokines and hormones. Those modulators may indirectly
      affect organ regeneration and other biological processes by controlling HGF
      production.

PMID- 8535211
TI  - Use of clodronate in multiple myeloma.
AB  - Multiple myeloma is characterized by bone disease including osteoporosis,
      osteolytic lesions, pathological fractures and hypercalcaemia leading to pain,
      immobilization and decrease in the quality of life. Clodronate, a bisphosphonate,
      has been shown to be effective in the treatment of hypercalcaemia in patients
      with multiple myeloma. In addition, clodronate reduces the progression of
      osteolytic lesions and the amount of vertebral fractures and may also relieve
      pain in these patients. Recent studies suggest that oral clodronate should be
      considered in the adjunctive treatment of all patients with active multiple
      myeloma independently of the presence of bone lesions at diagnosis. Due to its
      safety and efficacy, clodronate seems to have gained an important role in the
      management of patients with multiple myeloma.

PMID- 8535212
TI  - Chromosome 17 abnormalities and inactivation of the p53 gene in chronic myeloid
      leukemia and their prognostic significance.
AB  - We have reviewed all the relevant studies on the loss of the short arm of
      chromosome 17 (17p) and inactivation of the p53 gene in chronic myelogenous
      leukemia (CML) in an attempt to clarify their roles in the progression of CML.
      Loss of a 17p (hemizygous 17p) and p53 inactivation emerged as the disease
      progressed and were closely associated with each other. About half of the cases
      with loss of a 17p, however, did not show p53 inactivation. In these cases loss
      of a 17p preceded p53 inactivation, which suggested that either reduction of the
      p53 gene dosage or inactivation of another tumor-suppressor gene on 17p might
      contribute to the disease progression. Both loss of a 17p and p53 inactivation
      may serve as poor prognostic factors but the prognostic significance of the
      former only emerged when metaphase cells with loss of a 17p were dominant amongst
      the total cell population analyzed.

PMID- 8535213
TI  - Clinicopathological features, survival and prognostic factors of primary central
      nervous system lymphomas: trends in incidence of primary central nervous system
      lymphomas and primary malignant brain tumors in a well-defined geographical area.
      Population-based data from the Danish Lymphoma Registry, LYFO, and the Danish
      Cancer Registry.
AB  - It has been claimed that Primary Central Nervous System Lymphomas (PCNSL), a rare
      neoplasm accounting for only a small fraction of malignant brain tumors and
      extranodal non-Hodgkin lymphomas (NHL), occur with increasing frequency in
      immunologically normal as well as in immunocompromised individuals. In an attempt
      to characterize the clinicopathological features, outcome and prognostic factors
      of PCNSL we here report our experience in a large unselected series of patients
      from a well-defined region. In addition, we present data on trends in incidence
      of PCNSL and primary malignant brain tumors in a well-defined geographical area.
      In a Danish population-based NHL registry (LYFO) representing a population of 2.7
      million all new cases of NHL were registered during the approximate 11-year
      period from 1st January 1983 to 31st May 1994. Incidence data of primary
      malignant tumors of the brain and central nervous system in western Denmark for
      the period 1971-1990 have been obtained from the Danish Cancer Registry. During
      the approximate 11-year period 3124 new cases of NHL were registered. Of these,
      1152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for 4.2%
      of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence
      rate of non-AIDS related PCNSL during the period was 1.56 cases per million
      population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year
      period there was no trend towards an increasing incidence of non-AIDS related
      PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary
      malignant brain tumors. Incidence of primary malignant brain tumors was stable,
      except for age ranges over 70 years. However, diagnostic artifacts might be
      responsible for this apparent increase. Histologically, 85% were high grade.
      Using the Kiel classification centroblastic diffuse (60%) and immunoblastic
      lymphoma (13%) were the most common subtypes. Forty-three patients had B-cell
      lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed
      pre mortem. Treatment included surgical resection (26 patients), whole brain
      irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival
      for those receiving either WBRT or WBRT and chemotherapy was 8 months and 20
      months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at 1, 2
      and 5 years. Cox-regression analysis identified only one factor having
      independent impact on survival in PCNSL: performances score > or = 2 (p < 0.001,
      RR = 5.8).

PMID- 8535214
TI  - Quantitative expression of proliferating cell nuclear antigen by western blot
      (PCNAWB) in peripheral blasts correlates with remission induction in patients
      with acute myelogenous leukemia.
AB  - Proliferating cell nuclear antigen (PCNA) is a 36-kD nuclear protein that
      functions as a cofactor of delta DNA polymerase which is regulated in a cell
      cycle-dependent fashion. PCNA expression also increases when cells are actively
      engaged in DNA repair. We used Western blotting (WB) to measure the level of
      expression of PCNA in peripheral blasts of 36 adult acute myelogenous leukemia
      (AML) patients treated with Ara-C based induction regimens. PCNA levels
      correlated positively with the percentage of cells in S+G2M of the cell cycle.
      Logistic regression analysis revealed PCNA (beta = 4.5162; p = 0.0260) together
      with age (beta = 0.1777; p = 0.0364) as independent variables for remission
      induction: high PCNA levels were associated with poor response to induction
      therapy. PCNA expression was not, however, a predictor of survival in this subset
      of patients. We conclude that PCNA levels in this disease may be important for
      predicting response to Ara-C based remission induction chemotherapy.

PMID- 8535215
TI  - Soluble ICAM-1 in Hodgkin's disease: a promising independent predictive marker
      for survival.
AB  - The serum levels of soluble ICAM-1 (sICAM-1, sCD54) were significantly elevated
      (p = .0006) in patients with Hodgkin's disease (HD) (n = 101) compared to healthy
      controls (n = 31). Serum levels of sICAM-1 in HD correlated significantly with
      the presence of B-symptoms, histology and tumour burden as reflected in the Ann
      Arbor staging system, but not to bulky disease. sICAM-1 was compared to other
      serum factors claimed to be of prognostic significance in HD, including
      erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), deoxythymidine
      kinase (TK), soluble interleukin-2 receptor (sIL-2R, sCD25) and soluble CD30
      (sCD30, sKi-1-antigen). Serum levels of sICAM-1 correlated positively with all of
      these markers. In univariate regression analyses, all but ESR correlated with
      disease-free survival but only sICAM-1, sIL-2R and sCD30 correlated with overall
      survival. In multivariate analyses only sIL-2R (as a continuous variable) added
      independent prognostic information in addition to age, stage and B-symptoms.
      sICAM-1 and sCD30 approached significance (p = 0.07 and p = 0.08, respectively)
      for disease-free survival. sCD30 correlated with overall survival (p = 0.03)
      while sICAM-1 did not. When dichotomised at optimal cut-off levels, sICAM-1 as
      well as sIL-2R and sCD30 added independent prognostic information for both
      disease-free and overall survival. Based on the present observations, it appears
      that sICAM-1 may be a predictor for relapse and survival in HD. Determination of
      serum levels of sICAM-1 (in addition to sIL-2R and sCD30) may thus be of
      potential value when selecting HD patients eligible for intensive therapy in
      clinical trials.

PMID- 8535216
TI  - Proliferative fraction and DNA content are lower in B-cell non-Hodgkin's
      lymphomas with the t(14;18).
AB  - The t(14;18), which juxtaposes the immunoglobulin enhancer region from chromosome
      14 to the bcl-2 gene on chromosome 18, is a recurrent cytogenetic abnormality in
      the majority of follicular lymphomas (FL). This translocation results in
      overexpression of bcl-2, which increases cellular life span of the mutated cells
      by decreasing apoptosis. The t(14;18) also occurs in a subgroup of diffuse large
      cell lymphomas (DLCL), and current thought is that the majority of these
      represent transformation of FL. Low grade FL are characterized by low
      proliferation, and diploid/peridiploid DNA content. In this study, we compared
      proliferative activity (PF) and DNA content (DI) in FL containing the t(14;18) to
      DLCL with and without the t(14;18). The mean PF and DI were lower in the NHL
      containing t(14;18) irregardless of histologic subtype. We conclude that
      increased life span due to the presence of t(14;18) provides the conditions for
      accumulation of a different set of mutations as compared to those NHL developing
      from mutations in more rapidly proliferating precursors. This has implications
      for prognosis of patients with DLCL depending upon the presence or absence of
      t(14;18).

PMID- 8535217
TI  - Acute monocytic leukemia: a single institution experience.
AB  - Using strict FAB criteria, 39 cases of monocytic leukemia were identified in 463
      consecutive cases of AML. Patients had a median age of 49 with no sex
      predominance. Extramedullary disease and hyperleukocytosis were common (54% and
      36% of patients respectively). Cytogenetic analysis was successful in 38 of 39
      patients; 71% had a cytogenetic abnormality and 42% of these involved chromosome
      11; 14 of 16 chromosome 11 abnormalities involved the region of 11q23. Non
      chromosome 11 abnormalities tended to occur in older patients and to be
      associated with a lower platelet count; patients with the translocation 9;11
      tended to have a lower white count and a higher incidence of therapy-related
      leukemia. 35 patients were treated with induction therapy including intensive
      chemotherapy (n = 33) and allogeneic BMT at presentation (n = 2). Patients who
      entered remission underwent consolidation chemotherapy, autologous BMT, or
      allogeneic BMT depending on policies at the time of diagnosis. Of 6 patients who
      underwent further intensive chemotherapy there is 1 long-term disease-free
      survivor. 3 of 8 patients undergoing autologous BMT and 2 of 3 patients
      undergoing allogeneic BMT are long-term disease-free survivors. We conclude that
      this specific subtype of AML, relatively rare when strict criteria are applied,
      is associated with unique biologic and clinical features and that the high
      relapse rate associated with conventional therapy makes new treatment approaches
      involving stem cell transplantation or immunomodulation necessary.

PMID- 8535218
TI  - Regression of experimental human leukemias and solid tumors induced by Epstein
      Barr virus-immortalized B cells.
AB  - We previously have reported on an experimental athymic mouse model in which
      regression of human Burkitt's lymphoma is induced by either coinjection with or
      intratumor inoculation of Epstein-Barr virus (EBV)-immortalized human B cells. In
      the current study, we were interested in determining whether the powerful
      antitumor effects of EBV-immortalized B cells could be effective against a
      variety of human tumors grown in athymic mice, including acute lymphocytic
      leukemia, malignant melanoma, acute promyelocytic leukemia, neuroblastoma, lung
      carcinoma, colon adenocarcinoma, Wilms tumor, Hodgkin's lymphoma,
      rhabdomyosarcoma and breast adenocarcinoma. We report here the results of
      experiments in nude mice that demonstrated the potent antitumor effect of EBV
      immortalized B cells against human tumors derived from a variety of different
      tissues.

PMID- 8535219
TI  - All-trans retinoic acid in the treatment of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders
      characterized by uni- or multilineage maturation defects of the bone marrow.
      Controversial therapeutic results have been obtained using growth factors or
      differentiating agents such as 13-cis retinoic acid. In this pilot study we
      evaluated the effects of all-trans retinoic acid (ATRA) in 10 MDS patients (5
      male, 5 female). Six patients had refractory anemia (RA), 1 had refractory anemia
      with excess of blasts (RAEB), and 3 had refractory anemia with excess of blasts
      in transformation (RAEB-t). All patients received the same dose of ATRA (45
      mg/sqm/day) orally for 6 weeks. A rise in hemoglobin concentration > 1g/dl was
      observed in 3/10 patients, while 5/10 patients showed an increase in granulocyte
      count > 0.5 x 10(9)/l without concomitant increase in the percentage of blast
      cells in the bone marrow. A rise in the platelet count > 50 x 10(9)/l was
      observed in 1/10 patients. All the effects were transient and maximal responses
      were obtained by the fourth week of treatment. Thereafter, the peripheral blood
      counts started to drop again, reaching pre-therapy values by the end of the
      treatment. This phenomenon could be attributed either to the exhaustion of an
      ATRA-responding cell pool, the development of cellular resistance to ATRA or to a
      reduction of plasma ATRA levels after prolonged treatment. According to our
      results, it seems that ATRA might have therapeutic efficacy in MDS, particularly
      if its effect could be improved by combinations with other differentiating agents
      or growth factors.

PMID- 8535220
TI  - Cytokine receptor gene expression in peripheral blood mononuclear cells during
      graft-versus-host disease after allogeneic bone marrow transplantation.
AB  - Interleukin-1 receptor type 1 (IL-1R), IL-2 receptor alpha subunit (IL-2R) and IL
      6 receptor alpha subunit (IL-6R) mRNA expression in peripheral blood mononuclear
      cells (PBMC) in 17 patients who underwent allogeneic bone marrow transplantation
      (allo BMT) and 2 patients who underwent autologous transplantation were analyzed
      using a semiquantitative reverse-transcriptase polymerase chain reaction (RT
      PCR). There were several exceptions in some cases and IL-1R expression was found
      to vary in a rather wide range, however, the expression of IL-2R and IL-6R mRNA
      tended to increase during the development of graft-versus-host disease (GVHD). In
      particular, IL-2R mRNA expression was increased in four patients with GVHD and
      graft failure. In contrast, IL-2R and IL-6R mRNA expression was not increased in
      autologous (auto) BMT and auto peripheral blood stem cell transplantation (PBSCT)
      patients. These findings suggest that IL-2R and maybe IL-6R mRNA expression in
      PBMC play an important role in the development of an allo response and GVHD.
      Therefore, the analysis of cytokine receptor mRNA expression in PBMC after allo
      BMT may provide important information concerning the immune response and the
      cytokine network system in marrow transplants.

PMID- 8535221
TI  - Trisomy 12 in B-cell chronic lymphocytic leukemia: correlation with advanced
      disease, atypical morphology, high levels of sCD25, and with refractoriness to
      treatment.
AB  - In situ hybridization was performed to study the clinical significance of trisomy
      12 in fifty patients with B-cell chronic lymphocytic leukemia at various stages
      of disease. Trisomy 12 was detected in 12%-65% (median 53%) of the circulating
      neoplastic cells in seven out of 20 patients with advanced Binet stage C disease.
      In contrast, 22 patients with Binet stage A and eight patients with Binet stage B
      disease were found to be negative for trisomy 12. As occurrence of trisomy 12 was
      associated with the presence of B-symptoms and hepatosplenomegaly, its
      association with advanced disease was further considered. In addition, atypical
      morphology was a common finding in trisomic patients who also displayed higher
      serum levels of soluble CD25 than patients without trisomy at Binet stage C. No
      significant differences were detected in serum levels of soluble CD8 and of
      soluble CD23. No correlation with a lymphocyte doubling time of < 12 months,
      marked lymphadenopathy, or prior treatment was apparent. However, refractoriness
      to treatment was evident more frequently in trisomic than in non-trisomic
      patients (p < .05). In conclusion, trisomy 12 in B-cell chronic lymphocytic
      leukemia appears to occur predominantly in advanced and symptomatic disease with
      atypical morphology. It could indicate a high risk for treatment failure thus
      serving as a marker of poor prognosis in this disease.

PMID- 8535222
TI  - Expression of N-CAM (CD56) on acute leukemia cells: relationship with disease
      characteristics and outcome.
AB  - Expression of CD56 was analyzed by indirect immunofluorescence method on bone
      marrow samples from 94 newly diagnosed patients with acute leukemia (AL),
      including 59 acute myelogenous leukemias (AML) and 35 acute lymphoblastic
      leukemias (ALL). CD56 was expressed on 17 +/- 18% (range: 0-72%) of AML cells and
      24 +/- 24% (range: 0-98%) of ALL cells, without significant differences between
      FAB subtypes in AML, nor immunologic subtypes in ALL. Expression of CD56 was not
      associated with any clinical or biological characteristic at diagnosis, nor with
      prognosis in AML or ALL. We do not confirm previously described relationships
      between CD56 expression and initial characteristics and evolution of acute
      leukemia.

PMID- 8535223
TI  - Effect of anti-APO1 on spontaneous apoptosis of B cells in chronic lymphocytic
      leukaemia: the role of bcl-2 and interleukin 4.
AB  - The cell surface protein apolipoprotein 1 (APO1) is expressed on various cell
      types including malignant lymphoid cells. Triggering of APO1 protein with
      antibody (Ab) induces apoptosis in APO1-expressing cells. We examined the effect
      of anti (alpha) APO1 Ab on spontaneous apoptosis (SA) and bcl-2 expression in B
      cell chronic lymphocytic leukaemia (B-CLL) in vitro. We also investigated the
      anti-apoptotic activity of interleukin 4 (IL4) on the aAPO1-induced apoptosis in
      B-CLL cells. Although expression of APO1 on B-CLL cells was not detectable by
      immunofluorescence, alpha APO1 Ab induced apoptosis in these cells. At 24 hours
      in culture the number of apoptotic cells was increased by a mean percentage (%)
      of 27% (range: 21-38) in only half of the cases studied. But in all twelve cases
      studied, at 48 hours alpha APO1 increased SA by a mean of 72% (range: 26-114) (P
      < .001) and at 72 hours, the mean % increase was 69% (range: 31-96) in 6/7 cases
      (P < .001). This effect was alpha APO1 concentration dependent. Interleukin 4
      significantly protected B-CLL cells against alpha APO1-induced apoptosis by a
      mean of 53% (range: 28-76) (P < .001). This protection was specific to IL4 and it
      was significantly reduced or abolished with alpha IL4 Ab. Expression of bcl-2
      protein in untreated cultures was not significantly different from that of the
      alpha APO1-treated cells; the mean equivalent of soluble fluorochrome (MESF)
      (range) was 4.9 (3.0-6.8) and 5.2 (3.5-6.0) respectively (P > 0.2). In fresh B
      CLL cells the MESF (range) was 4.5 (2.4-6.6). Thus alpha APO1 Ab induced
      apoptosis in B-CLL cells by a pathway that is independent of bcl-2 expression and
      partially blocked by IL4.

PMID- 8535224
TI  - Immunophenotype and ultrastructural studies in blast crisis of chronic myeloid
      leukemia.
AB  - Thirty-four patients with chronic myeloid leukemia in blast crisis (CML-BC) were
      evaluated for lineage differentiation with immunological markers and the presence
      of ultrastructural peroxidase. Eighteen (52.9%) were found to have myeloid blast
      crisis. Cytochemically, myeloperoxidase (MPO) could be detected only in six
      patients on light microscopy while in the remaining 12 patients, myeloid
      differentiation was confirmed only by demonstration of MPO either at
      ultrastructural level or by the reactivity with anti myeloperoxidase (anti MPO)
      antibody. Six (17.6%) had lymphoid blast crisis as identified by lymphoid
      specific markers (CD19; CD10; CD7; CD4) along with the absence of myeloid
      markers. Heterogenous blast cell populations with mixed lineage differentiation
      were seen in 4 (11.7%) patients. These cases showed both lymphoid (CD19, CD10)
      and myeloid (anti MPO and ultrastructural MPO) characteristics. A single case of
      megakaryoblastic blast crisis was identified with positivity for CD41 and CD42
      along with the presence of platelet peroxidase at the ultrastructural level. Five
      cases (14%) of CML blast crisis remained unclassifiable. These results suggest
      that blast crisis in CML show an arrest of differentiation at an early stage when
      compared to de novo acute leukemias. This is particularly evident from the fact
      that MPO could only be demonstrated ultrastructurally or with anti MPO antibody
      in the majority of patients with myeloid differentiation. It is expected that
      utilisation of molecular studies including immunoglobulin and T-cell receptor
      gene rearrangement and m-RNA expression for myeloperoxidase will provide a better
      insight into the level of differentiation for the presently unclassifiable cases
      of CML-blast crisis.

PMID- 8535225
TI  - Circulating colony-forming units of granulocytes/monocytes in patients with
      chronic myeloid leukemia before and during busulfan treatment.
AB  - The number of colony-forming units of granulocytes/monocytes (CFU-GM) in the
      peripheral blood of 7 patients with chronic myeloid leukemia (CML) in chronic
      phase (CP) receiving standard doses of busulfan (BSF, 0.1-0.2 mg/kg/day p.o.) was
      compared to that found in 8 patients with CML in CP not previously treated in
      order to establish if non-myeloablative chemotherapy mobilizes committed
      granulomonocytic progenitor cells into the circulation. The number (mean +/- SEM)
      of spontaneous CFU-GM in untreated patients was similar to that recorded in 10
      sex- and age-matched controls, 2.6 +/- 1.9 and 3.5 +/- 2.1, respectively. BSF
      treated patients showed significantly more spontaneous CFU-GM (13.9 +/- 7.5) than
      controls and untreated patients. Addition of recombinant human
      granulocyte/monocyte colony-stimulating factor to cultures promoted colony growth
      in controls but not in untreated and BSF-treated patients. These data seemingly
      indicate that: 1) administration of standard non-myeloablative doses of BSF to
      patients with CML in CP mobilizes CFU-GM into the circulation and 2) BSF therapy
      selects a granulomonocytic colony-forming progenitor cell population with
      increased autonomous growth potential. These findings may contribute to the
      understanding of the therapeutic role of BSF in CML.

PMID- 8535226
TI  - Antiproliferative effect of human interleukin-4 in human cancer cell lines:
      studies on the mechanism.
AB  - Interleukin-4 (IL-4) plays an important role in activating the immune system
      against malignant cells. The human interleukin-4 receptor (hIL-4R) is not only
      expressed by hematopoietic cells but also on a large number of tissue specimens
      which include colon, breast and lung carcinomas. In this study we report that
      rhIL-4 has an antiproliferative effect on 2 out of 3 non-small cell lung
      carcinoma (NSCLC) cell lines in vitro as measured by human tumor cloning assays
      (HTCA). In comparison, rhIL-4 had no effect on the growth of small cell lung
      carcinoma cell lines (SCLC) in vitro. The response towards the cytokine is
      correlated with expression of at least 1500 high affinity receptors/cell for hIL
      4 on the responsive cell lines. Xenotransplanting the human lung tumor cell lines
      into nude mice followed by 12 days of systemic treatment of the mice with rhIL-4
      revealed a significant growth retardation of the IL-4R positive NSCLC cell lines
      when compared with the controls, whereas the growth of the IL-4R negative SCLC
      cell lines was unaffected also in vivo. Studies of possible mechanisms involved
      in the antiproliferative effect of rhIL-4 showed that rhIL-4 does not induce
      apoptosis or modulation of the transcription factor c myc in the responsive NSCLC
      cell lines. Additionally, the expression of the epidermal growth factor receptor
      (EGFR), which is discussed as mediating autocrine/paracrine growth stimulation of
      NSCLC, is unaffected by rhIL-4. However, we have observed that rhIL-4 inhibited
      G1-S-phase cell cycle progression. We conclude that rhIL-4 has an
      antiproliferative effect on the growth of some NSCLC in vitro and in vivo. The
      mechanisms involved remain to be further elucidated.

PMID- 8535227
TI  - Phase III comparative trial using CHOP vs CIOP in the treatment of advanced
      intermediate-grade non-Hodgkin's lymphoma.
AB  - Until now, literature data support the fact that the CHOP regimen represents the
      standard first line treatment for patients with advanced intermediate-grade non
      Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials
      because of its favourable preclinical profile: it is more active than
      daunorubicin and doxorubicin against a number of experimental tumour systems and
      is significantly less cardiotoxic in animal models. From March 1991 to June 1993,
      115 previously untreated patients with stage II to IV intermediate-grade non
      Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a
      phase III comparative trial. The objectives of the study were to compare the
      efficacy and safety of using idarubicin instead of doxorubicin in the
      polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine,
      and dexamethasone). Of the 115 patients registered for the trial, 103 were
      evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known
      prognostic factors were equally distributed among the two groups. There were no
      significant differences between the 2 groups in the rates of partial and complete
      response. The overall response rate was 87%, with complete response in 62%: 63%
      in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months),
      86% of all CR patients were alive without disease in the CHOP group and 85% in
      the CIOP group. Patients treated with CHOP experienced severe alopecia more
      frequently (P = .004). Only three patients in the CIOP group showed cardiac
      adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2
      moderate and 1 severe were recorded. LVEF monitoring was carried out in 31
      patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of
      the LVEF was observed in patients treated with CHOP regimen as compared to 4.8%
      in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm"
      (CIOP regimen) was found to have an equivalent therapeutic efficacy and,
      slightly, reduced clinical toxicity in comparison to the standard doxorubicin
      containing CHOP regimen in patients with intermediate-grade non-Hodgkin's
      lymphoma.

PMID- 8535228
TI  - Treatment of Waldenstrom's macroglobulinemia with very low doses of alpha
      interferon.
AB  - Waldenstrom's macroglobulinemia (WM) is a differentiated B-cell malignancy which
      is usually less responsive to standard chemotherapy because of low-proliferating
      cells. Interferon alpha has been shown to possess a therapeutic action in
      numerous B-cell malignancies including the early stage of chronic lymphocytic
      leukemia, multiple myeloma, follicular lymphoma and hairy cell leukemia. Fourteen
      patients with progressive WM were included in a pilot study using very low dose
      of interferon alpha-2a (1 Million Units 3 times a week). The mean duration of
      treatment was 10.3 months (range 2-44). Six of 14 (42%) patients presented an
      increase in the hemoglobin level (> or = 0.9 g/dL) and 4/14 (28%) had a
      substantial decrease of the monoclonal component (> or = 20% of reduction). Only
      two patients presented both types of response, while the others with an increase
      in the hemoglobin level had a slight decrease in the monoclonal component (MC) (1
      patient), a stable MC (1 patient) or a slight increase of MC (1 patient). One
      additional patient had a 15% decrease of the MC with a stable hemoglobin level.
      Response was observed within 3 months with a median duration of 6 months.
      Treatment was stopped for 3 patients because of flu-like symptoms (2 patients),
      or thrombocytopenia (1 patient). Follow up was possible in 12 patients lasting up
      to a maximum of 30 months after discontinuing treatment. Seven patients died,
      including 4 with progressive disease, two of infection and one of cardiac
      failure. In the view of these results, very low dose of interferon alpha may
      constitute a new approach for treatment of some cases of WM.

PMID- 8535229
TI  - Recombinant human interleukin-6 accelerates in-vitro megakaryocytopoiesis and
      platelet recovery post autologous peripheral blood stem cell transplantation.
AB  - Prolonged thrombocytopenia complicated by bleeding episodes represent a major
      problem following autologous bone marrow transplantation (ABMT). Recombinant
      human interleukin-6 (rhIL-6) has been shown to be a maturation factor for both
      mouse and human megakaryocytes. We administered rhIL-6 to a 43 year old woman who
      developed marked resistant and prolonged thrombocytopenia with bleeding episodes
      following autologous peripheral blood stem cell transplantation (APBSCT). Twenty
      days after the initiation of rhIL-6 therapy, the number of megakaryocyte (MK)
      progenitors (CFU-MK and BFU-MK) cultured from the peripheral blood increased
      followed by a moderate increase in the number of bone marrow megakaryocytes. The
      platelet count increased and the bleeding episodes disappeared. Although
      spontaneous platelet recovery cannot be ruled out in this case it seems that rhIL
      6 may be an important thrombopoietic factor for severe thrombocytopenia following
      APBSCT.

PMID- 8535230
TI  - Double isochromosome 8q as single cytogenetic aberration in acute myelo-monocytic
      leukemia.
AB  - We report a case of double isochromosome 8q as a single cytogenetic abnormality
      in a patient with acute myelo-monocytic leukemia. Similarly to rare cases with
      tetrasomy 8, the patient showed monocytic involvement and was refractory to
      cytotoxic chemotherapy. We conclude that this kind of cytogenetic aberration is
      probably associated with distinct morphologic and clinical characteristics.

PMID- 8535231
TI  - Tetrasomy of chromosome 8 in a patient with acute myeloid leukemia.
AB  - We report a case of acute myeloid leukaemia (AML), FAB classification M2,
      associated with tetrasomy 8. This chromosomal aberration was detected using
      conventional cytogenetics and flourescent in-situ hybridization (FISH). Using
      FISH, the pre-treatment cells with tetrasomy 8 were disomic for chromosome 7. A
      small number of tetrasomy 8 cells were found post-treatment, but these were
      tetrasomic for chromosome 7. The significance of this is considered, and the
      literature regarding tetrasomy 8 in acute myeloid leukaemia is reviewed.

PMID- 8535232
TI  - Structural analysis of zinc substitutions in the active site of thermolysin.
AB  - Native thermolysin binds a single catalytically essential zinc ion that is
      tetrahedrally coordinated by three protein ligands and a water molecule. During
      catalysis the zinc ligation is thought to change from fourfold to fivefold.
      Substitution of the active-site zinc with Cd2+, Mn2+, Fe2+, and Co2+ alters the
      catalytic activity (Holmquist B, Vallee BL, 1974, J Biol Chem 249:4601-4607).
      Excess zinc inhibits the enzyme. To investigate the structural basis of these
      changes in activity, we have determined the structures of a series of metal
      substituted thermolysins at 1.7-1.9 A resolution. The structure of the Co(2+)
      substituted enzyme is shown to be very similar to that of wild type except that
      two solvent molecules are liganded to the metal at positions that are thought to
      be occupied by the two oxygens of the hydrated scissile peptide in the transition
      state. Thus, the enhanced activity toward some substrates of the cobalt-relative
      to the zinc-substituted enzyme may be due to enhanced stabilization of the
      transition state. The ability of Zn2+ and Co2+ to accept tetrahedral coordination
      in the Michaelis complex, as well as fivefold coordination in the transition
      state, may also contribute to their effectiveness in catalysis. The Cd(2+)- and
      Mn(2+)-substituted thermolysins display conformational changes that disrupt the
      active site to varying degrees and could explain the associated reduction of
      activity. The conformational changes involve not only the essential catalytic
      residue, Glu 143, but also concerted side-chain rotations in the adjacent
      residues Met 120 and Leu 144. Some of these side-chain movements are similar to
      adjustments that have been observed previously in association with the "hinge
      bending" motion that is presumed to occur during catalysis by the zinc
      endoproteases. In the presence of excess zinc, a second zinc ion is observed to
      bind at His 231 within 3.2 A of the zinc bound to native thermolysin, explaining
      the inhibitory effect.

PMID- 8535233
TI  - Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and
      of the C-truncated proenzyme.
AB  - The proteolytic enzyme stromelysin-1 is a member of the family of matrix
      metalloproteinases and is believed to play a role in pathological conditions such
      as arthritis and tumor invasion. Stromelysin-1 is synthesized as a pro-enzyme
      that is activated by removal of an N-terminal prodomain. The active enzyme
      contains a catalytic domain and a C-terminal hemopexin domain believed to
      participate in macromolecular substrate recognition. We have determined the three
      dimensional structures of both a C-truncated form of the proenzyme and an
      inhibited complex of the catalytic domain by X-ray diffraction analysis. The
      catalytic core is very similar in the two forms and is similar to the homologous
      domain in fibroblast and neutrophil collagenases, as well as to the stromelysin
      structure determined by NMR. The prodomain is a separate folding unit containing
      three alpha-helices and an extended peptide that lies in the active site of the
      enzyme. Surprisingly, the amino-to-carboxyl direction of this peptide chain is
      opposite to that adopted by the inhibitor and by previously reported inhibitors
      of collagenase. Comparison of the active site of stromelysin with that of
      thermolysin reveals that most of the residues proposed to play significant roles
      in the enzymatic mechanism of thermolysin have equivalents in stromelysin, but
      that three residues implicated in the catalytic mechanism of thermolysin are not
      represented in stromelysin.

PMID- 8535234
TI  - Structural similarity between the pleckstrin homology domain and verotoxin: the
      problem of measuring and evaluating structural similarity.
AB  - An unexpected structural similarity is described between the pleckstrin homology
      (PH) domain and verotoxin. This similarity has escaped detection primarily due to
      the differences in topology that exist between the two proteins. By comparing
      this result with two previously reported similarities for the PH domain, one with
      the lipocalins and another with the FK506 binding protein, we discuss the
      problems of measuring and assessing structural similarities.

PMID- 8535235
TI  - Water molecules participate in proteinase-inhibitor interactions: crystal
      structures of Leu18, Ala18, and Gly18 variants of turkey ovomucoid inhibitor
      third domain complexed with Streptomyces griseus proteinase B.
AB  - Crystal structures of the complexes of Streptomyces griseus proteinase B (SGPB)
      with three P1 variants of turkey ovomucoid inhibitor third domain (OMTKY3),
      Leu18, Ala18, and Gly18, have been determined and refined to high resolution.
      Comparisons among these structures and of each with native, uncomplexed SGPB
      reveal that each complex features a unique solvent structure in the S1 binding
      pocket. The number and relative positions of water molecules bound in the S1
      binding pocket vary according to the size of the side chain of the P1 residue.
      Water molecules in the S1 binding pocket of SGPB are redistributed in response to
      the complex formation, probably to optimize hydrogen bonds between the enzyme and
      the inhibitor. There are extensive water-mediated hydrogen bonds in the
      interfaces of the complexes. In all complexes, Asn 36 of OMTKY3 participates in
      forming hydrogen bonds, via water molecules, with residues lining the S1 binding
      pocket of SGPB. For a homologous series of aliphatic straight side chains, Gly18,
      Ala18, Abu18, Ape18, and Ahp18 variants, the binding free energy is a linear
      function of the hydrophobic surface area buried in the interface of the
      corresponding complexes. The resulting constant of proportionality is 34.1 cal
      mol-1 A-2. These structures confirm that the binding of OMTKY3 to the preformed
      S1 pocket in SGPB involves no substantial structural disturbances that commonly
      occur in the site-directed mutagenesis studies of interior residues in other
      proteins, thus providing one of the most reliable assessments of the contribution
      of the hydrophobic effect to protein-complex stability.

PMID- 8535236
TI  - Crystal structure of thioltransferase at 2.2 A resolution.
AB  - We report here the first three-dimensional structure of a mammalian
      thioltransferase as determined by single crystal X-ray crystallography at 2.2 A
      resolution. The protein is known for its thiol-redox properties and
      dehydroascorbate reductase activity. Recombinant pig liver thioltransferase
      expressed in Escherichia coli was crystallized in its oxidized form by vapor
      diffusion technique. The structure was determined by multiple isomorphous
      replacement method using four heavy-atom derivatives. The protein folds into an
      alpha/beta structure with a four-stranded mixed beta-sheet in the core, flanked
      on either side by helices. The fold is similar to that found in other thiol-redox
      proteins, viz. E. coli thioredoxin and bacteriophage T4 glutaredoxin, and thus
      seems to be conserved in these functionally related proteins. The active site
      disulfide (Cys 22-Cys 25) is located on a protrusion on the molecular surface.
      Cys 22, which is known to have an abnormally low pKa of 3.8, is accessible from
      the exterior of the molecule. Pro 70, which is in close proximity to the
      disulfide bridge, assumes a conserved cis-peptide configuration. Mutational data
      available on the protein are in agreement with the three-dimensional structure.

PMID- 8535237
TI  - De novo design of the hydrophobic cores of proteins.
AB  - We have developed and experimentally tested a novel computational approach for
      the de novo design of hydrophobic cores. A pair of computer programs has been
      written, the first of which creates a "custom" rotamer library for potential
      hydrophobic residues, based on the backbone structure of the protein of interest.
      The second program uses a genetic algorithm to globally optimize for a low energy
      core sequence and structure, using the custom rotamer library as input. Success
      of the programs in predicting the sequences of native proteins indicates that
      they should be effective tools for protein design. Using these programs, we have
      designed and engineered several variants of the phage 434 cro protein, containing
      five, seven, or eight sequence changes in the hydrophobic core. As controls, we
      have produced a variant consisting of a randomly generated core with six sequence
      changes but equal volume relative to the native core and a variant with a
      "minimalist" core containing predominantly leucine residues. Two of the designs,
      including one with eight core sequence changes, have thermal stabilities
      comparable to the native protein, whereas the third design and the minimalist
      protein are significantly destabilized. The randomly designed control is
      completely unfolded under equivalent conditions. These results suggest that
      rational de novo design of hydrophobic cores is feasible, and stress the
      importance of specific packing interactions for the stability of proteins. A
      surprising aspect of the results is that all of the variants display highly
      cooperative thermal denaturation curves and reasonably dispersed NMR spectra.
      This suggests that the non-core residues of a protein play a significant role in
      determining the uniqueness of the folded structure.

PMID- 8535238
TI  - Prediction of polyelectrolyte polypeptide structures using Monte Carlo
      conformational search methods with implicit solvation modeling.
AB  - Many interesting proteins possess defined sequence stretches containing
      negatively charged amino acids. At present, experimental methods (X-ray
      crystallography, NMR) have failed to provide structural data for many of these
      sequence domains. We have applied the dihedral probability grid-Monte Carlo (DPG
      MC) conformational search algorithm to a series of N- and C-capped
      polyelectrolyte peptides, (Glu)20, (Asp)20, (PSer)20, and (PSer-Asp)10, that
      represent polyanionic regions in a number of important proteins, such as
      parathymosin, calsequestrin, the sodium channel protein, and the acidic
      biomineralization proteins. The atomic charges were estimated from charge
      equilibration and the valence and van der Waals parameters are from DREIDING.
      Solvation of the carboxylate and phosphate groups was treated using sodium
      counterions for each charged side chain (one Na+ for COO-; two Na for CO(PO3)-2)
      plus a distance-dependent (shielded) dielectric constant, epsilon = epsilon 0 R,
      to simulate solvent water. The structures of these polyelectrolyte polypeptides
      were obtained by the DPG-MC conformational search with epsilon 0 = 10, followed
      by calculation of solvation energies for the lowest energy conformers using the
      protein dipole-Langevin dipole method of Warshel. These calculations predict a
      correlation between amino acid sequence and global folded conformational minima:
      1. Poly-L-Glu20, our structural benchmark, exhibited a preference for right
      handed alpha-helix (47% helicity), which approximates experimental observations
      of 55-60% helicity in solution. 2. For Asp- and PSer-containing sequences, all
      conformers exhibited a low preference for right-handed alpha-helix formation (<
      or = 10%), but a significant percentage (approximately 20% or greater) of beta
      strand and beta-turn dihedrals were found in all three sequence cases: (1) Aspn
      forms supercoil conformers, with a 2:1:1 ratio of beta-turn:beta-strand:alpha
      helix dihedral angles; (2) PSer20 features a nearly 1:1 ratio of beta-turn:beta
      sheet dihedral preferences, with very little preference for alpha-helical
      structure, and possesses short regions of strand and turn combinations that give
      rise to a collapsed bend or hairpin structure; (3) (PSer-Asp)10 features a 3:2:1
      ratio of beta-sheet:beta-turn:alpha-helix and gives rise to a superturn or C
      shaped structure.

PMID- 8535239
TI  - Binary patterning of polar and nonpolar amino acids in the sequences and
      structures of native proteins.
AB  - Protein sequences can be represented as binary patterns of polar ([symbol: see
      text]) and nonpolar ([symbol: see text]) amino acids. These binary sequence
      patterns are categorized into two classes: Class A patterns match the structural
      repeat of an idealized amphiphilic alpha-helix (3.6 residues per turn), and class
      B patterns match the structural repeat of an idealized amphiphilic beta-strand (2
      residues per turn). The difference between these two classes of sequence patterns
      has led to a strategy for de novo protein design based on binary patterning of
      polar and nonpolar amino acids. Here we ask whether similar binary patterning is
      incorporated in the sequences and structures of natural proteins. Analysis of the
      Protein Data Bank demonstrates the following. (1) Class A sequence patterns occur
      considerably more frequently in the sequences of natural proteins that would be
      expected at random, but class B patterns occur less often than expected. (2) Each
      pattern is found predominantly in the secondary structure expected from the
      binary strategy for protein design. Thus, class A patterns are found more
      frequently in alpha-helices than in beta-strands, and class B patterns are found
      more frequently in beta-strands than in alpha-helices. (3) Among the alpha
      helices of natural proteins, the most commonly used binary patterns are indeed
      the class A patterns. (4) Among all beta-strands in the database, the most
      commonly used binary patterns are not the expected class B patterns. (5) However,
      for solvent-exposed beta-strands, the correlation is striking: All beta-strands
      in the database that contain the class B patterns are exposed to
      solvent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535240
TI  - Posttranslational modifications of bovine osteopontin: identification of twenty
      eight phosphorylation and three O-glycosylation sites.
AB  - Osteopontin (OPN) is a multiphosphorylated glycoprotein found in bone and other
      normal and malignant tissues, as well as in the physiological fluids urine and
      milk. The present study demonstrates that bovine milk osteopontin is
      phosphorylated at 27 serine residues and 1 threonine residue. Phosphoamino acids
      were identified by a combination of amino acid analysis, sequence analysis of S
      ethylcysteine-derivatized phosphopeptides, and mass spectrometric analysis.
      Twenty-five phosphoserines and one phosphothreonine were located in Ser/Thr-X
      Glu/Ser(P)/Asp motifs, and two phosphoserines were found in the sequence Ser-X-X
      Glu/Ser(P). These sequence motifs are identical with the recognition sequences of
      mammary gland casein kinase and casein kinase II, respectively. Examination of
      the phosphorylation pattern revealed that the phosphorylations were clustered in
      groups of approximately three spanned by unphosphorylated regions of 11-32 amino
      acids. This pattern is probably of importance in the multiple functions of OPN
      involving interaction with Ca2+ and inorganic calcium salts. Furthermore, three O
      glycosylated threonines (Thr 115, Thr 124, and Thr 129) have been identified in a
      threonine- and proline-rich region of the protein. Three putative N-glycosylation
      sites (Asn 63, Asn 85, and Asn 193) are present in bovine osteopontin, but
      sequence and mass spectrometric analysis showed that none of these asparagines
      were glycosylated in bovine mammary gland osteopontin. Alignment analysis showed
      that the majority of the phosphorylation sites in bovine osteopontin as well as
      all three O-glycosylation sites were conserved in other mammalian sequences. This
      conservation of serines, even in otherwise less well-conserved regions of the
      protein, indicates that the phosphorylation of osteopontin at specific sites is
      essential for the function of the protein.

PMID- 8535241
TI  - Thermal stability determinants of chicken egg-white lysozyme core mutants:
      hydrophobicity, packing volume, and conserved buried water molecules.
AB  - A series of 24 mutants was made in the buried core of chicken lysozyme at
      positions 40, 55, and 91. The midpoint temperature of thermal denaturation
      transition (Tm) values of these core constructs range from 60.9 to 77.3 degrees
      C, extending an earlier, more limited investigation on thermostability. The Tm
      values of variants containing conservative replacements for the wild type (WT)
      (Thr 40-Ile 55-Ser 91) triplet are linearly correlated with hydrophobicity (r =
      0.81) and, to a lesser degree, with combined side-chain volume (r = 0.75). The X
      ray structures of the S91A (1.9 A) and I55L/S91T/D101S (1.7 A) mutants are
      presented. The former amino acid change is found in duck and mammalian lysozymes,
      and the latter contains the most thermostable core triplet. A network of four
      conserved, buried water molecules is associated with the core. It is postulated
      that these water molecules significantly influence the mutational tolerance at
      the individual triplet positions. The pH dependence of Tm for the S91D mutant was
      compared with that of WT enzyme. The pKa of S91D is 1.2 units higher in the
      native than in the denatured state, corresponding to delta delta G298 = 1.7
      kcal/mol. This is a low value for charge burial and likely reflects the
      moderating influence of the buried water molecules or a conformational change.
      Thermal and chemical denaturation and far UV CD spectroscopy were used to
      characterize the in vitro properties of I55T. This variant, which buries a
      hydroxyl group, has similar properties to those of the human amyloidogenic
      variant I56T.

PMID- 8535242
TI  - Design and structural analysis of an engineered thermostable chicken lysozyme.
AB  - A hyperstable (hs) variant of chicken egg-white lysozyme with enhanced thermal
      (delta Tm approximately +10.5 degrees C) and chemical (delta Cm for guanidine
      hydrochloride denaturation = +1.3 M) stabilities relative to wild-type (WT) was
      constructed by combining several individual stabilizing substitutions. The free
      energy difference between the native and denatured states of the hs variant is
      3.1 (GdnHCl, 25 degrees C) to 4.0 (differential scanning calorimetry, 74 degrees
      C) kcal mol-1 greater than that of WT. The specific activity of the hs variant is
      2.5-fold greater than that of WT. The choice of mutations came from diverse
      sources: (1) The I55L/S91T core construct with delta Tm = 3.3 degrees C from WT
      was available from the accompanying study (Shih P, Holland DR, Kirsch JF, 1995,
      Protein Sci 4:2050-2062). (2) The A31V mutation was suggested by the better
      atomic packing in the human lysozyme structure where the Ala 31 equivalent is
      Leu. (3) The H15L and R114H substitutions were selected on the basis of sequence
      comparisons with pheasant lysozymes that are more stable than the chicken enzyme.
      (4) The D101S variant was identified from a screen of mutants previously prepared
      in this laboratory. The effects of the individual mutations on stability are
      cumulative and nearly additive.

PMID- 8535243
TI  - Destabilizing loop swaps in the CDRs of an immunoglobulin VL domain.
AB  - It is generally believed that loop regions in globular proteins, and particularly
      hypervariable loops in immunoglobulins, can accommodate a wide variety of
      sequence changes without jeopardizing protein structure or stability. We show
      here, however, that novel sequences introduced within complementarity determining
      regions (CDRs) 1 and 3 of the immunoglobulin variable domain REI VL can
      significantly diminish the stability of the native state of this protein. Besides
      their implications for the general role of loops in the stability of globular
      proteins, these results suggest previously unrecognized stability constraints on
      the variability of CDRs that may impact efforts to engineer new and improved
      activities into antibodies.

PMID- 8535244
TI  - Identification of iron ligands in tyrosine hydroxylase by mutagenesis of
      conserved histidinyl residues.
AB  - Tyrosine hydroxylase catalyzes the hydroxylation of tyrosine and other aromatic
      amino acids using a tetrahydropterin as the reducing substrate. The enzyme is a
      homotetramer; each monomer contains a single nonheme iron atom. Five histidine
      residues are conserved in all tyrosine hydroxylases that have been sequenced to
      date and in the related eukaryotic enzymes phenylalanine and tryptophan
      hydroxylase. Because histidine has been suggested as a ligand to the iron in
      these enzymes, mutant tyrosine hydroxylase proteins in which each of the
      conserved histidines had been mutated to glutamine or alanine were expressed in
      Escherichia coli. The H192Q, H247Q, and H317A mutant proteins contained iron in
      comparable amounts to the wild-type enzyme, about 0.6 atoms/sub-unit. In
      contrast, the H331 and H336 mutant proteins contained no iron. The first three
      mutant enzymes were active, with Vmax values 39, 68, and 7% that of the wild-type
      enzyme, and slightly altered V/Km values for both tyrosine and 6
      methyltetrahydropterin. In contrast, the H331 and H336 mutant enzymes had no
      detectable activity. The EPR spectra of the H192Q and H247Q enzymes are
      indistinguishable from that of wild-type tyrosine hydroxylase, whereas that of
      the H317A enzyme indicated that the ligand field of the iron had been slightly
      perturbed. These results are consistent with H331 and H336 being ligands to the
      active site iron atom.

PMID- 8535245
TI  - Atomic solvation parameters in the analysis of protein-protein docking results.
AB  - Several sets of amino acid surface areas and transfer free energies were used to
      derive a total of nine sets of atomic solvation parameters (ASPs). We tested the
      accuracy of each of these sets of parameters in predicting the experimentally
      determined transfer free energies of the amino acid derivatives from which the
      parameters were derived. In all cases, the calculated and experimental values
      correlated well. We then chose three parameter sets and examined the effect of
      adding an energetic correction for desolvation based on these three parameter
      sets to the simple potential function used in our multiple start Monte Carlo
      docking method. A variety of protein-protein interactions and docking results
      were examined. In the docking simulations studied, the desolvation correction was
      only applied during the final energy calculation of each simulation. For most of
      the docking results we analyzed, the use of an octanol-water-based ASP set
      marginally improved the energetic ranking of the low-energy dockings, whereas the
      other ASP sets we tested disturbed the ranking of the low-energy dockings in many
      of the same systems. We also examined the correlation between the experimental
      free energies of association and our calculated interaction energies for a series
      of proteinase-inhibitor complexes. Again, the octanol-water-based ASP set was
      compatible with our standard potential function, whereas ASP sets derived from
      other solvent systems were not.

PMID- 8535246
TI  - Characterization of the isolated cAMP-binding B domain of cAMP-dependent protein
      kinase.
AB  - A 14.4-kDa cAMP-binding fragment was generated during bacterial expression and
      purification of recombinant bovine cAMP-dependent protein kinase type I alpha
      regulatory subunit (RI alpha). The full-length RI alpha from which the fragment
      was derived contained a point mutation allowing its B domain to bind both cAMP
      and cGMP with high affinity while leaving its A domain highly cAMP selective. The
      NH2 terminus of the fragment was Ser-252, indicating that it encompassed the
      entire predicted B domain. Although the [3H]cAMP and [3H]cGMP exchange rates of
      the isolated B domain were increased relative to the B domain in intact RI alpha,
      the [3H]cAMP exchange rate was comparable to that of the B domain of full-length
      RI alpha containing an unoccupied A domain. A plasmid encoding only the isolated
      B domain was overexpressed in Escherichia coli, and a monomeric form of the B
      domain was purified that had identical properties to the proteolytically
      generated fragment, indicating that all of the elements for the high-affinity
      cAMP-binding B domain are contained within the 128 amino acid carboxyl terminus
      of the R subunit. Prolonged induction of the B domain in E. coli or storage of
      the purified protein resulted in the formation of a dimer that could be reverted
      to the monomer by incubation in 2-mercaptoethanol. Dimerization caused an
      approximate fivefold increase in the rate of cyclic nucleotide exchange relative
      to the monomer. The results show that an isolated cAMP-binding domain can
      function independently of any other domain structures of the R subunit.

PMID- 8535247
TI  - Are proteins ideal mixtures of amino acids? Analysis of energy parameter sets.
AB  - Various existing derivations of the effective potentials of mean force for the
      two-body interactions between amino acid side chains in proteins are reviewed and
      compared to each other. The differences between different parameter sets can be
      traced to the reference state used to define the zero of energy. Depending on the
      reference state, the transfer free energy or other pseudo-one-body contributions
      can be present to various extents in two-body parameter sets. It is, however,
      possible to compare various derivations directly by concentrating on the "excess"
      energy-a term that describes the difference between a real protein and an ideal
      solution of amino acids. Furthermore, the number of protein structures available
      for analysis allows one to check the consistency of the derivation and the errors
      by comparing parameters derived from various subsets of the whole database. It is
      shown that pair interaction preferences are very consistent throughout the
      database. Independently derived parameter sets have correlation coefficients on
      the order of 0.8, with the mean difference between equivalent entries of 0.1 kT.
      Also, the low-quality (low resolution, little or no refinement) structures show
      similar regularities. There are, however, large differences between interaction
      parameters derived on the basis of crystallographic structures and structures
      obtained by the NMR refinement. The origin of the latter difference is not yet
      understood.

PMID- 8535248
TI  - C alpha-based torsion angles: a simple tool to analyze protein conformational
      changes.
AB  - A simple method is presented for the analysis of protein conformational changes
      based on the comparison of torsion angles defined by four consecutive C alpha
      atoms. The technique was applied successfully to proteins that undergo hinge
      motion and shear motion. In the case of both MBP and LAO, which represent
      examples of hinge motion, the plot of the differences in C alpha-torsion angles
      between the open and closed forms of the proteins helped us to formulate a more
      thorough description of the conformational change: a large displacement of one
      domain with respect to the other where one of the domains does not behave like a
      rigid body but exhibits some degree of flexibility. The analysis of citrate
      synthase, which is an example of shear motion, shows that the largest differences
      in C alpha-torsion angles between the open and closed conformations are clustered
      around residues that belong to segments connecting alpha-helices, whereas the
      helices themselves appear to be rigid; this is in agreement with previous results
      obtained by detailed least-squares superpositions (Lesk AM, Chothia C, 1984, J
      Mol Biol 174:175-191).

PMID- 8535249
TI  - Relative effectiveness of various anions on the solubility of acidic Hypoderma
      lineatum collagenase at pH 7.2.
AB  - The effects of various anions on decreasing the solubility of acidic Hypoderma
      lineatum collagenase at pH 7.2 and 18 degrees C were qualitatively defined by
      replacing the crystallizing agent of known crystallization conditions by various
      ammonium salts. The solubility curves measured in the presence of the sulfate,
      phosphate, citrate, and chloride ammonium salts gave the following ranking of
      anions: HPO4(2-)/H2PO4- > SO4(2-) > citrate 3-/citrate2- >> Cl-. This order is in
      agreement with the Hofmeister series. In a previous study on the solubility at pH
      4.5 of lysozyme, a basic protein, the effectiveness of anions in decreasing the
      solubility was found to be in the reverse order. This suggests that the
      effectiveness of anions in the crystallization of proteins is dependent on the
      net charge of the protein, i.e., depending on whether a basic protein is
      crystallized at acidic pH or an acidic protein at basic pH.

PMID- 8535250
TI  - Thrombin-binding affinities of different disulfide-bonded isomers of the fifth
      EGF-like domain of thrombomodulin.
AB  - The fifth EGF-like domain of thrombomodulin (TM), both with and without the amino
      acids that connect the fifth domain to the sixth domain, has been synthesized and
      refolded to form several different disulfide-bonded isomers. The domain without
      the connecting region formed three disulfide-bonded isomers upon refolding under
      redox conditions. Of these three isomers, the (1-2,3-4,5-6) bonded isomer was the
      best inhibitor of fibrinogen clotting and also of the thrombin-TM interaction
      that results in protein C activation, but all the isomers were inhibitors in both
      assays. The isomer containing an EGF-like disulfide-bonding pattern (1-3,2-4,5-6)
      was not found among the oxidation products. The domain with the connecting region
      amino acids (DIDE) at the C-terminus formed two isolable products upon refolding
      in redox buffer. These products had the same two disulfide-bonding patterns as
      the earliest and latest eluting isomers of the domain without the DIDE. In order
      to compare the thrombin-binding affinities of these isomers to the isomer with
      the EGF-like disulfide bonds, acetamidomethyl protection of the second and fourth
      cysteines was used to force the disulfide bonds into the EGF-like pattern.
      Thrombin-binding affinity, measured as inhibition of fibrinogen clotting and as
      inhibition of protein C activation correlated inversely with the number of
      crossed disulfide bonds. As was found for the domain without the connecting
      region, the isomer that was the best inhibitor of fibrinogen clotting and of
      protein C activation was the isomer with no crossing disulfide bonds (1-2,3-4,5
      6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535252
TI  - Production, purification, and crystallization of human interleukin-1 beta
      converting enzyme derived from an Escherichia coli expression system.
AB  - Interleukin-1 beta converting enzyme (ICE) is a cysteine protease that catalyzes
      the conversion of the inactive precursor form of IL-1 beta to an active mature
      form. The mature form of IL-1 beta is involved in mediating inflammatory
      responses and in the progression of autoimmune diseases. We recently reported on
      the production of active human ICE in insect cells using the baculovirus
      expression system (Wang XM et al., 1994, Gene 145:273-277). Because the levels of
      expression achieved with this system were limiting for the purpose of performing
      detailed biochemical and biophysical studies, we examined the production of ICE
      in Escherichia coli. By using a tac promoter-based expression system and fusion
      to thioredoxin we were able to recover high levels of active ICE protein. The
      expressed protein, which was distributed between the soluble and insoluble
      fractions, was purified to homogeneity from both fractions using a combination of
      classical and affinity chromatography. Comparisons of ICE derived from both
      fractions indicated that they were comparable in their specific activities,
      subunit composition, and sensitivities to specific ICE inhibitors. The combined
      yields of ICE obtained from the soluble and insoluble fractions was close to 1
      mg/L of induced culture. Recombinant human ICE was crystallized in the presence
      of a specific ICE inhibitor in a form suitable for X-ray crystallographic
      analysis. This readily available source of ICE will facilitate the further
      characterization of this novel and important protease.

PMID- 8535251
TI  - Denaturant m values and heat capacity changes: relation to changes in accessible
      surface areas of protein unfolding.
AB  - Denaturant m values, the dependence of the free energy of unfolding on denaturant
      concentration, have been collected for a large set of proteins. The m value
      correlates very strongly with the amount of protein surface exposed to solvent
      upon unfolding, with linear correlation coefficients of R = 0.84 for urea and R =
      0.87 for guanidine hydrochloride. These correlations improve to R = 0.90 when the
      effect of disulfide bonds on the accessible area of the unfolded protein is
      included. A similar dependence on accessible surface area has been found
      previously for the heat capacity change (delta Cp), which is confirmed here for
      our set of proteins. Denaturant m values and heat capacity changes also correlate
      well with each other. For proteins that undergo a simple two-state unfolding
      mechanism, the amount of surface exposed to solvent upon unfolding is a main
      structural determinant for both m values and delta Cp.

PMID- 8535253
TI  - The role of glutamate 87 in the kinetic mechanism of Thermus thermophilus
      isopropylmalate dehydrogenase.
AB  - The kinetic mechanism of the oxidative decarboxylation of 2R,3S-isopropylmalate
      by the NAD-dependent isopropylmalate dehydrogenase of Thermus thermophilus was
      investigated. Initial rate results typical of random or steady-state ordered
      sequential mechanisms are obtained for both the wild-type and two mutant enzymes
      (E87G and E87Q) regardless of whether natural or alternative substrates (2R
      malate, 2R,3S-tartrate and/or NADP) are utilized. Initial rate data fail to
      converge on a rapid equilibrium-ordered pattern despite marked reductions in
      specificity (kcat/Km) caused by the mutations and alternative substrates.
      Although the inhibition studies alone might suggest an ordered kinetic mechanism
      with cofactor binding first, a detailed analysis reveals that the expected
      noncompetitive patterns appear uncompetitive because the dissociation constants
      from the ternary complexes are far smaller than those from the binary complexes.
      Equilibrium fluorescence studies both confirm the random binding of substrates
      and the kinetic estimates of the dissociation constants of the substrates from
      the binary complexes. The latter are not distributed markedly by the mutations at
      site 87. Mutations at site 87 do not affect the dissociation constants from the
      binary complexes, but do greatly increase the Michaelis constants, indicating
      that E87 helps stabilize the Michaelis complex of the wild-type enzyme. The
      available structural data, the patterns of the kinetics results, and the
      structure of a pseudo-Michaelis complex of the homologous isocitrate
      dehydrogenase of Escherichia coli suggest that E87 interacts with the
      nicotinamide ring.

PMID- 8535254
TI  - Homology modeling of an immunoglobulin-like domain in the Saccharomyces
      cerevisiae adhesion protein alpha-agglutinin.
AB  - The Saccharomyces cerevisiae adhesion protein alpha-agglutinin is expressed by
      cells of alpha mating type. On the basis of sequence similarities, alpha
      agglutinin has been proposed to contain variable-type immunoglobulin-like (IgV)
      domains. The low level of sequence similarity to IgV domains of known structure
      made homology modeling using standard sequence-based alignment algorithms
      impossible. We have therefore developed a secondary structure-based method that
      allowed homology modeling of alpha-aggulutinin domain III, the domain most
      similar to IgV domains. The model was assessed and where necessary refined to
      accommodate information obtained by biochemical and molecular genetic approaches,
      including the positions of a disulfide bond, glycosylation sites, and proteolytic
      sites. The model successfully predicted surface exposure of glycosylation and
      proteolytic sites, as well as identifying residues essential for binding
      activity. One side of the domain was predicted to be covered by carbohydrate
      residues. Surface accessibility and volume packing analyses showed that the
      regions of the model that have greatest sequence dissimilarity from the IgV
      consensus sequence are poorly structured in the biophysical sense. Nonetheless,
      the utility of the model suggests that these alignment and testing techniques
      should be of general use for building and testing of models of proteins that
      share limited sequence similarity with known structures.

PMID- 8535256
TI  - Modeling conformational changes in cyclosporin A.
AB  - NMR and X-ray structures for the immunosuppressant cyclosporin A (CsA) reveal a
      remarkable difference between the unbound (free) conformation in organic solvents
      and the conformation bound to cyclophilin. We have performed computer simulations
      of the molecular dynamics of CsA under a variety of conditions and confirmed the
      stability of these two conformations at room temperature in water and in vacuum.
      However, when the free conformation was modeled in vacuum at 600 K, a transition
      pathway leading to the bound conformation was observed. This involved a change in
      the cis MeLeu-9 peptide bond to a trans conformation and the movement of the side
      chains forming the dominant hydrophobic cluster (residues MeBmt-1, MeLeu-4, MeLeu
      6, and MeLeu-10) to the opposite side of the plane formed by the backbone atoms
      in the molecular ring. The final conformation had a backbone RMS deviation from
      the bound conformation of 0.53 A and was as stable in dynamics simulations as the
      bound conformation. Our calculations allowed us to make a detailed analysis of a
      transition pathway between the free and the bound conformations of CsA and to
      identify two distinct regions of coordinated movement in CsA, both of which
      underwent transitions independently.

PMID- 8535255
TI  - Alignment of 700 globin sequences: extent of amino acid substitution and its
      correlation with variation in volume.
AB  - Seven-hundred globin sequences, including 146 nonvertebrate sequences, were
      aligned on the basis of conservation of secondary structure and the avoidance of
      gap penalties. Of the 182 positions needed to accommodate all the globin
      sequences, only 84 are common to all, including the absolutely conserved PheCD1
      and HisF8. The mean number of amino acid substitutions per position ranges from 8
      to 13 for all globins and 5 to 9 for internal positions. Although the total
      sequence volumes have a variation approximately 2-3%, the variation in volume per
      position ranges from approximately 13% for the internal to approximately 21% for
      the surface positions. Plausible correlations exist between amino acid
      substitution and the variation in volume per position for the 84 common and the
      internal but not the surface positions. The amino acid substitution matrix
      derived from the 84 common positions was used to evaluate sequence similarity
      within the globins and between the globins and phycocyanins C and colicins A, via
      calculation of pairwise similarity scores. The scores for globin-globin
      comparisons over the 84 common positions overlap the globin-phycocyanin and
      globin-colicin scores, with the former being intermediate. For the subset of
      internal positions, overlap is minimal between the three groups of scores. These
      results imply a continuum of amino acid sequences able to assume the common three
      on-three alpha-helical structure and suggest that the determinants of the latter
      include sites other than those inaccessible to solvent.

PMID- 8535257
TI  - Molecular modeling studies of HIV-1 reverse transcriptase nonnucleoside
      inhibitors: total energy of complexation as a predictor of drug placement and
      activity.
AB  - Computer modeling studies have been carried out on three nonnucleoside inhibitors
      complexed with human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      (RT), using crystal coordinate data from a subset of the protein surrounding the
      binding pocket region. Results from the minimizations of solvated complexes of 2
      cyclopropyl-4-methyl-5,11-dihydro-5H-dipyrido[3,2-b :2',3'-e][1,4] diazepin-6-one
      (nevirapine), alpha-anilino-2, 6-dibromophenylacetamide (alpha-APA), and 8-chloro
      tetrahydro-imidazo(4,5,1-jk)(1,4)-benzodiazepin-2(1H)-thi one (TIBO) show that
      all three inhibitors maintain a very similar conformational shape, roughly
      overlay each other in the binding pocket, and appear to function as pi-electron
      donors to aromatic side-chain residues surrounding the pocket. However, side
      chain residues adapt to each bound inhibitor in a highly specific manner, closing
      down around the surface of the drug to make tight van der Waals contacts.
      Consequently, the results from the calculated minimizations reveal that only when
      the inhibitors are modeled in a site constructed from coordinate data obtained
      from their particular RT complex can the calculated binding energies be relied
      upon to predict the correct orientation of the drug in the pocket. In the correct
      site, these binding energies correlate with EC50 values determined for all three
      inhibitors in our laboratory. Analysis of the components of the binding energy
      reveals that, for all three inhibitors, solvation of the drug is endothermic, but
      solvation of the protein is exothermic, and the sum favors complex formation. In
      general, the protein is energetically more stable and the drug less stable in
      their complexes as compared to the reactant conformations. For all three
      inhibitors, interaction with the protein in the complex is highly favorable.
      Interactions of the inhibitors with individual residues correlate with
      crystallographic and site-specific mutational data. pi-Stacking interactions are
      important in binding and correlate with drug HOMO RHF/6-31G* energies. Modeling
      results are discussed with respect to the mechanism of complex formation and the
      design of nonnucleoside inhibitors that will be more effective against mutants of
      HIV-1 RT that are resistant to the currently available drugs.

PMID- 8535258
TI  - Molecular modeling of the GM-CSF and IL-3 receptor complexes.
AB  - A model for the structure of the cytokine interleukin-3 (IL-3) is presented based
      on the structural homology of the hematopoietic cytokines and utilizing the
      crystal structures of interleukin-5 and granulocyte macrophage colony stimulating
      factor (GM-CSF). In addition, models of the receptor complexes of GM-CSF and IL-3
      are presented based on the structural homology of the hematopoietic receptors to
      growth hormone. Several key interactions between the ligands and their receptors
      are discovered, some in agreement with previous mutagenesis studies and others
      that have not yet been the subject of mutagenesis studies. The models provide
      insights into the binding of GM-CSF and IL-3 to their receptors.

PMID- 8535259
TI  - Urease activity in the crystalline state.
AB  - Crystalline Klebsiella aerogenes urease was found to have less than 0.05% of the
      activity observed for the soluble enzyme under standard assay conditions. Li2SO4,
      present in the crystal storage buffer at 2 M concentration, was shown to inhibit
      soluble urease by a mixed inhibition mechanism (Ki's of 0.38 +/- 0.05 M for the
      free enzyme and 0.13 +/- 0.02 M for the enzyme-urea complex). However, the
      activity of crystals was less than 0.5% of the expected value, suggesting that
      salt inhibition does not account for the near absence of crystalline activity.
      Dissolution of crystals resulted in approximately 43% recovery of the soluble
      enzyme activity, demonstrating that protein denaturation during crystal growth
      does not cause the dramatic diminishment in the catalytic rate. Finally, crushed
      crystals exhibited only a three-fold increase in activity over that of intact
      crystals, indicating that the rate of substrate diffusion into the crystals does
      not significantly limit the enzyme activity. We conclude that urease is
      effectively inactive in this crystal form, possibly due to conformational
      restrictions associated with a lid covering the active site, and propose that the
      small amounts of activity observed arise from limited enzyme activity at the
      crystal surfaces or trace levels of enzyme dissolution into the crystal storage
      buffer.

PMID- 8535260
TI  - [Directed chemical modification of DNA fragments by perfluorarylazide derivatives
      of oligonucleotides in the presence of oligonucleotides bearing photosensitized
      pyrene groups].

PMID- 8535261
TI  - [Study of the lac repressor, bound to DNA, by a method of covalent DNA-protein
      crosslinking].

PMID- 8535262
TI  - [Clastogenic effect of mycoplasma on human chromosomes].

PMID- 8535264
TI  - [Non-equilibrium population genetics dynamics].

PMID- 8535263
TI  - [Modification of the functional activity of neutrophils by a synthetic peptide
      from the V3-loop of the HIV envelope protein gp120].

PMID- 8535265
TI  - [Immunomodulating properties of biologically active substances from embryonic
      tissue from birds of the chicken family].

PMID- 8535266
TI  - [Interferons cause accumulation of diadenosine triphosphate (Ap3A) in human
      monocyte cultures].

PMID- 8535267
TI  - [Identification of genes, predominantly expressed during early stages of murine
      hemopoiesis].

PMID- 8535268
TI  - [A new approach to mapping short DNA sequences using electron microscopy].

PMID- 8535269
TI  - [Isolation and characteristics of repeat DNA sequences from precentromere
      heterochromatin from the second chromosome of Drosophila melanogaster].

PMID- 8535270
TI  - [Repeating tetradecameric nucleotide sequences in mycoplasma genomes].

PMID- 8535271
TI  - [Daily and seasonal changes in temperature and cardiac rhythm of the long-tailed
      squirrel, Citellus undulatus].

PMID- 8535272
TI  - [Primary structure of the nucleocapsid gene C and the protein coded by it from
      the Western equine encephalomyelitis virus].

PMID- 8535273
TI  - [Change in expression and inheritance of the marker gene nptII in progeny of
      Nicotiana tabacum L transgenic plants].

PMID- 8535274
TI  - [Change in tinctorial and energetic properties of hepatocytes during adaptation
      to changes in culture conditions].

PMID- 8535275
TI  - [Change in the ultrastructure of sea urchin oocytes exposed to dimethyl
      sulfoxide].

PMID- 8535276
TI  - [Structure-activity dependence in a series of synthetic analogs of ACTH fragment
      (5-7)].

PMID- 8535277
TI  - [Effect of short-term stimulation of muscles on affinity of hemoglobin for oxygen
      in cats].

PMID- 8535278
TI  - [Drosophila retrotransposon mdg3: general structure and functional domains of a
      full-scale copy].

PMID- 8535280
TI  - [Effect of 1-chloromethylsilantrane on the level of minerals in bone calluses due
      to fractures in the tibial long bone].

PMID- 8535279
TI  - [Reconstruction of a section of the electron transfer chain, including cytochrome
      b561, an acidic copper-containing protein, and dopamine-beta-monooxygenase, in
      chromaffin granule membranes].

PMID- 8535281
TI  - [Effect of adrenaline on ion currents through potential-directed calcium channels
      in frog myoblasts].

PMID- 8535282
TI  - [Coenzyme Q (ubiquinone) as a behavioural modifier in rats, subjected to low
      background ionizing radiation].

PMID- 8535283
TI  - Anandamide, an endogenous cannabinomimetic substance, modulates rat brain protein
      kinase C in vitro.
AB  - Anandamide (AnNH, N-arachidonoyl-ethanolamine) has been recently proposed as the
      endogenous ligand for mammalian brain cannabinoid receptor. Non-cannabinoid
      receptor-mediated, intracellular actions have been also found for this novel
      mediator. Here we present evidence for the modulation by anandamide of rat brain
      protein kinase C (PKC) activity in vitro. The ethanolamide of arachidonic acid
      (AA) was more active than the free acid in increasing phosphatidylserine (PS)
      induced PKC activation (EC50 = 40 microM), but inhibited dioleylglycerol-induced
      potentiation of both Ca(2+)- and Ca2+/PS-induced PKC activation (IC50 = 8 microM
      and 30 microM, respectively). A dual modulatory action of anandamide on PKC,
      exerted by binding to the diacylglycerol regulatory site, is hypothesized in rat
      brain.

PMID- 8535284
TI  - Coexpression of the myc gene family members in human neuroblastoma cell lines.
AB  - Members of the myc oncogene family such as c, N-, and L-myc are expressed in many
      malignant tumors. Expression of c-, N-, and L-myc oncogenes in 7 human
      neuroblastoma cell lines (GOTO, IMR-32, TGW, SCCH-26, TNB 9, NBL-S, and SK-N-SH),
      a human small cell lung carcinoma SBC-5 cell line, and a human monocytic leukemia
      THP-1-S cell line at mRNA and protein levels was studied to know the specificity
      of a newly developed antibody against homologous region at C-terminus of N-Myc,
      designated as anti pan-Myc antibody. By RT-PCR and immunoblot analysis,
      coexpression of three myc genes was detected in all neuroblastoma cell lines
      tested. c-and L-myc expression were observed that anti pan-Myc antibody
      recognizes c-Myc and N-Myc proteins but not L-Myc. These results indicate that
      neuroblastoma cells may acquire an aberrant transcriptional control system in myc
      family gene expression.

PMID- 8535285
TI  - Isolation of ERp72 from guinea pig term placentae using heparin Sepharose
      affinity chromatography.
AB  - The mammalian placenta synthesises many varied antigens, including proteins, such
      as hormones, enzymes and protease inhibitors. In this report, we isolated and
      purified the two protein isomerase-related protein precursor ERp72 isoforms from
      aqueous extracts of guinea pig placenta, by four (4) chromatographic procedures;
      i) affinity chromatography on immobilised heparin, ii) gel filtration (Ultrogel
      AcA-54), iii) anion exchange chromatography (Mono-Q), and, iv) negative
      immunoaffinity chromatography. From 20 term placentae, the final yield of ERp72
      isoforms was 2.4mg (Mr 71.5 kDa) and 1.5mg (Mr 75.8 kDa). Identity was confirmed
      by NH2-terminal amino acid sequencing which demonstrated 85% homology to human
      ERp72. By indirect immunofluorecence. ER p72 expression was demonstrated in
      tunicamycin stressed pre-implantation embryos and unfertilised oocytes. These
      findings demonstrate the potential for immunological monitoring of ERp72
      expression, by cultured oocytes and embryos, during manipulation by assisted
      reproductive technologies.

PMID- 8535286
TI  - 1H NMR studies of peptide fragments from the N-terminus of chicken and human
      transthyretin.
AB  - Two synthetic peptides corresponding to N-terminal fragments of human and chicken
      transthyretin have been synthesized and their structures examined in solution
      using 1H NMR spectroscopy. Complete sequence-specific assignments obtained for
      the two peptides are reported together with coupling constant and nuclear
      Overhauser data. The peptides were found to adopt random-coil conformations in
      aqueous solution. This is consistent with findings from X-ray structures of the
      native human transthyretin where the N-terminal region could not be defined,
      presumably because of conformational disorder.

PMID- 8535287
TI  - A rapid redistribution of transferrin receptors to the cell surface of L2C
      lymphocytes upon fixation of holoform transferrin.
AB  - The internalization and recycling kinetics of transferrin receptors in leukemic
      lymphocytes (L2C) differed in the absence or presence of ligand. At 37 degrees C
      in the absence of ligand, transferrin receptors were mainly distributed
      internaly. We demonstrated, using a sepharose-bead-Tf complex, the rapid
      recycling of unoccupied internal transferrin receptors was correlated with ligand
      binding to surface receptors. The recycling amplitude was related to the
      occupancy of iron ligated transferrin to plasma membrane surface receptors.
      Contrary to the results obtained with other cells, redistribution of Tf receptors
      was not triggered by binding of other ligands to their receptors.

PMID- 8535288
TI  - Transformation of cadmium-binding complexes during cadmium sequestration in
      fission yeast.
AB  - Fission yeast responded to environmental cadmium by producing a family of small
      Cd-binding peptides, phytochelatins (PCn). A low molecular weight (LMW) complex
      essentially composed of PC2, and PC3 was produced and then disappeared gradually
      in 24 hrs after Cd treatment, which served as a transient form for a temporary
      but quick relief of Cd in the cytosoL It had been reported that the LMW complex
      was further transported into the vacuole by an ABC-type protein (HMT1), and a
      higher molecular weight (HMW) complex was formed in the vacuole. Results from gel
      filtration chromatography and HPLC analysis showed that the transformation of the
      LMW to the HMW complex was accompanied with a rearrangement of its PCn component.
      Besides, the molecular conformation of the HMW complex changed from a relaxed
      form in the early stage to a more condensed conformation during cell aging. And
      the transformation of the LMW into the HMW complex by the addition of sulfide in
      the test tube was demonstrated.

PMID- 8535289
TI  - Hydrophobic interaction and folding propensity of chicken heart apocytochrome c.
AB  - In contrast to horse heart apocytochrome c, the chicken one showed quite
      different folding propensity as titrated by NaCl at different pH. At pH 2.0,
      folding behaviour of both apocytochrome c are essentially similar; while at pH
      higher than 4.0, chicken heart apocytochrome c has much enhanced propensity to
      fold and aggregate, as was shown by circular dichroism spectra, intrinsic
      fluorescence and non-denatured polyacrylamide gel electrophoresis. Hydrophobic
      chromatography demonstrated much higher hydrophobicity of chicken heart
      apocytochrome c, thus strongly suggested that it is the hydrophobic interaction
      that stabilize the 'Molten Globule' like, partially-folded structure of chicken
      heart apocytochrome c at neutral pH.

PMID- 8535290
TI  - Cloning and high-level expression of chicken apocytochrome c gene in Escherichia
      coli.
AB  - Chicken apocytochrome c gene with correct reading frame was easily cloned through
      excision by polymerase chain reaction of the intron in the genomic clone of
      chicken cytochrome c gene, and was successfully overexpressed in Escherichia coli
      by cloning into expression vector pET-3d under the control of T7 promoter.
      Expressed protein can amount to as high as 40% of the total protein and mainly
      presents as inclusion body. Purification of chicken apocytochrome c from the
      inclusion body and characterization by SDS-PAGE, isoelectric focusing
      electrophoresis, and amino acid analysis showed that the purified apocytochrome c
      is identical to that prepared from chicken heart cytochrome c by chemically
      depletion of heme.

PMID- 8535291
TI  - Association of cytoskeletal proteins with estrogen receptor in rat uterine
      cytosol: possible role in receptor movement into the nucleus.
AB  - Evidence is presented to demonstrate a close association between an estrogen
      receptor or an estrogen receptor activation factor and the cytoskeletal proteins,
      tubulin and actin in rat uterine cytosol. Exposure of uterine cytosol to protein
      kinase assay medium resulted in the phosphorylation of three proteins, of
      molecular mass 55, 50 and 45 kDa. These 55 and 50 kDa proteins apparently
      represent tubulin, while the 45 kDa protein, is presumed to be actin.
      Phosphorylation of these proteins is under the regulatory influence of estradiol
      and the cyclic nucleotides, cAMP and cGMP. It is proposed that the protein kinase
      involved in this process may be the non-activated estrogen receptor (naER).

PMID- 8535292
TI  - Half-site reactivity with p-nitrophenylhydrazine and subunit separation of the
      dimeric copper-containing amine oxidase from Aspergillus niger.
AB  - Structural properties of dimeric (2 x 75 kDa) copper-containing amine oxidase (EC
      1.4.3.6) from Aspergillus niger were studied. The enzyme treated with SDS was
      dissociated into subunits which showed different mobility on polyacrylamide gel
      without SDS. The separated subunits had no activity but a quinone moiety was
      detected in both by a redox-cyclic quinone staining. After titration of the
      enzyme with p-nitrophenylhydrazine, which showed half-site reactivity (1 mole per
      dimer), and SDS treatment both p-nitro-phenylhydrazone and a remaining quinone
      moiety were detected in each subunit. It is suggested that the half-site
      reactivity with phenylhydrazine is caused by conformational changes after binding
      of the inhibitor to any one of the active sites leading to inaccessibility of the
      second active site for the inhibitor. The difference in electrophoretic mobility
      of the separated subunits originates probably from their structural difference
      likely to occur outside the active site, even if the amino acid sequences of the
      subunits appear to be identical.

PMID- 8535293
TI  - Effect of trehalose during stress in a heat-shock resistant mutant of
      Saccharomyces cerevisiae.
AB  - Cells of a heat-shock resistant mutant were approximately 1000-times more
      resistant to lethal heat shock than those of the parental strain. We observed
      that exponentially growing cells of the mutant synthesized trehalose and showed
      increased osmotolerance, dehydration tolerance an ethanol tolerance, a fact not
      observed in wild type strains. The mutant synthesizes constitutively six
      proteins, among them two proteins of 56 and 63 kDa. Interestingly these molecular
      weights could correspond to the subunit of trehalose-6-phosphate synthase and to
      phosphoglucomutase II, respectively. Our results showed that glucose-growing
      cells of the hsr 1 mutant possessed high levels of activity of these enzymes when
      compared to the control strain.

PMID- 8535295
TI  - Secretion is a stimulus for the synthesis of human chorionic gonadotrophin by
      first trimester human placenta.
AB  - Time course of release of immunoreactive hCG to a placental incubation in the
      medium revealed a steady increase over a period of 4 hours. However, levels in
      the tissue, showed an increase at 10' and 60' after an initial decrease. Studies
      using A23187 which stimulated secretion also revealed a net increase in the
      quantity of hCG in the tissue. These results suggest that the secretion of hCG
      acts as a stimulus for fresh synthesis of hCG.

PMID- 8535294
TI  - Effects of divalent cations and nucleotides on the 14CO2-oxaloacetate exchange
      catalyzed by the phosphoenol pyruvate carboxykinase from the moderate halophile,
      Vibrio costicola.
AB  - The phosphoenolpyruvate carboxykinase (PEPCK) from Vibrio costicola catalyzed a
      14CO2-oxaloacetate exchange reaction with an unusual nucleotide specificity. ATP
      gave the higher apparent catalytic efficiency (Vmax/Km, 6.78), followed by GTP
      (1.30), CTP (0.87) and ITP (0.66). Maximal activity required a divalent cation;
      CdCl2 and MgCl2 synergistically activated the enzyme, when added in the presence
      of MnCl2. The sigmoidal saturation curve for MnCl2 (apparent n 2.11) was
      converted into a hyperbola by 0.01 mM CdCl2 (apparent n 1). The results suggest a
      double role of the divalent cation in the reaction mechanism, namely as part of
      the MeATP2- substrate and as free Me2+. Mn2+ would be the best for the first, and
      Cd2+ for the second role. Preincubation with 0.01 mM CdCl2 increased the activity
      of the enzyme assayed with MgATP2- through an increase in Vmax; addition of CdCl2
      to the reaction mixture elicited further activation, through a 17-fold decrease
      in the apparent Km for MgATP2-. These results, together with the biphasic curve
      of activation by CdCl2 when used alone, suggest the existence of two different
      sites for free Cd2+ on the enzyme.

PMID- 8535296
TI  - Mercuric chloride effects on the kinetic parameters of human erythrocyte membrane
      bound acetylcholinesterase.
AB  - Kinetic analysis of the interaction of mercuric chloride with human erythrocyte
      acetylcholinesterase was investigated in the present study. It was found that
      mercuric chloride reversibly inhibited the AChE activity in a concentration
      dependent manner, the IC50 being 16 microM while the IC100 was 47 microM. The Km
      for the hydrolysis of acetylthiocholine iodide by AChE was found to be 97 microM
      in the control system, and the value increased by 16-144% in the mercuric
      chloride treated systems. The Vmax was 1.72 mumol/min/mg protein for the control
      as well as the mercuric chloride treated systems. Dixon as well as Lineweaver
      Burke plots and their secondary replots indicated that the nature of the
      inhibition is of the reversible competitive type. The K(i) value was estimated as
      6.26 microM. The K(i) value increased with an increase in substrate
      concentration.

PMID- 8535297
TI  - Purification of LamB proteins using continuous elution electrophoresis: a
      comparison with immunoaffinity chromatography.
AB  - LamB is a membrane protein that allows the exposition of a foreign peptide on the
      surface of a recombinant E. coli cells. An immunopurified hybrid LamB protein has
      been used to elicit high-titre antibodies to a foreign epitope. Looking for a
      simpler purification procedure we have compared the traditional approach, which
      includes affinity chromatography, to continuous elution electrophoresis, in the
      purification of two different hybrid LamB proteins as foreign epitopes. The
      results obtained showed that both methods yielded the same purification, although
      the electrophoretic procedure had a higher yield. Continuous-elution
      electrophoresis could be a useful tool for the purification of membrane proteins.

PMID- 8535298
TI  - Bio-Catalyzer alpha . rho No. 11 (Bio-Normalizer) supplementation: effect on
      oxidative stress to isolated rat hearts.
AB  - Bio-Catalyzer alpha . rho No. 11 (Bio-Normalizer), a natural health food product
      prepared by yeast fermentation of medicinal plants, has been recently reported to
      possess antioxidant properties. To better define its antioxidant action, we
      investigated the effects of orally supplemented Bio-Normalizer on oxidative
      damage in the rat heart. Hearts were isolated from control or Bio-Normalizer
      supplemented animals and 1) exposed to ischemia-reperfusion using the Langendorff
      technique, or 2) homogenized and exposed to peroxyl radicals generated from (2,2'
      azobis (2,4'-dimethylvaleronitrile) (AMVN). During reperfusion following 40
      minutes of ischemia, leakage of lactate dehydrogenase from hearts isolated from
      Bio-Normalizer supplemented rats was significantly lower than from hearts of
      control animals. Furthermore, lower levels of AMVN-induced accumulation of
      thiobarbituric acid reactive substances and of protein carbonyl derivatives were
      measured in homogenates prepared from hearts isolated from Bio-Normalizer
      supplemented rats than in samples from control animals. Our findings confirm an
      antioxidant action of Bio-Normalizer and show that it protects the heart against
      ischemia-reperfusion induced damage.

PMID- 8535299
TI  - Lysosomal glycosidases in different populations of human thymocytes.
AB  - Lysosomal glycosidase activities were studied in human thymocyte fractions
      obtained by two methods: (A) fractionation in Percoll density gradient and (B)
      separation from the cells forming rosettes with sheep erythrocytes (E-RFC). (A)
      affords fraction L, enriched with immature and endogenously activated thymocytes,
      and fraction H containing mature thymocytes. By use of (B), fraction E-RFC-
      enriched with non-activated immature thymocytes--was obtained. Comparative study
      of E-RFC and H revealed diverse alterations in activities of glycosidases during
      thymocytes maturation, specifically decreases in alpha-L-fucosidase and alpha-D
      mannosidase and an increase in beta-D-galactosidase. Comparing E-RFC and L
      demonstrates increases in activities of studied glycosidases following endogenous
      activation of thymocytes.

PMID- 8535300
TI  - Activation of human beta-glucuronidase by murine monoclonal antibodies and bovine
      serum albumin in an uncompetitive fashion.
AB  - Catalytic antiidiotypic antibodies exhibit enzyme activity because they possess
      the internal image of the enzyme that serves as the antigen. However, we have
      found that non-catalytic monoclonal antibodies specific for human beta
      glucuronidase and, to a lesser extent, bovine serum albumin were capable of
      enhancing the activity of this enzyme. The stability of the enzyme was not
      increased by these proteins. Enzyme kinetic studies revealed an uncompetitive
      activation mechanism with a proportional increase in both maximal velocity and
      Michaelis constant of the enzyme with the increase in the protein concentration.
      These three proteins apparently bound to the enzyme with subsequent alteration of
      its affinity for the substrate. Activation of the enzyme by its non-catalytic
      antibody might not be a rare occurrence and it could play a pathogenic role in
      certain disease processes.

PMID- 8535301
TI  - NADP-malic enzyme from maize leaves: a fluorescence study.
AB  - NADP-malic enzyme from maize leaves is covalently labeled with a fluorescent-SH
      reactive probe eosin-5-maleimide (EMA), which reacts with groups that are totally
      protected by NADP against inactivation. The comparison of the emission
      fluorescence spectra of the native and the modified enzyme suggests the proximity
      of the fluorescent groups of the native enzyme (probably tryptophanyl groups) and
      the EMA modified residues. Intrinsic fluorescence quenching studies shows that
      NADP is the only substrate capable to interact with the fluorescent excited
      groups of the enzyme, while Mg2+ is able to increase this interaction. Quenching
      studies of EMA-bound fluorescence shows that the NADP-binding site was modified
      and thus uncapable of further interaction with the nucleotide. When the results
      of protection studies are combined with those of extrinsic quenching experiments,
      we must conclude that EMA reacts with sulfhydryl groups that are involved in the
      NADP-binding site of the enzyme.

PMID- 8535302
TI  - Effect of the pyrethroid insecticide allethrin on membrane fluidity.
AB  - Allethrin is a widely used pyrethroid insecticide with an
      alkenylmethylcyclopentenolone group in its structure. We have analyzed its
      interaction with model and native membranes using DPH and its polar derivative
      TMA-DPH fluorescence polarization. Allethrin modified the bilayer order in the
      temperature range of the phase transition when incorporated into liposomes made
      with dimyristoyl-(DMPC), dipalmitoyl-(DPPC) and distearoyl-(DSPC)
      phosphatidylcholine. In DMPC: allethrin mixtures the pyrethroid decreased the
      bilayer order in the gel phase, without altering the liquid-crystalline one. In
      native membranes, DPH and TMA-DPH fluorescence polarization remained unchanged
      after incubation with allethrin. The release of hemoglobin was notably
      facilitated by the incorporation of allethrin into human erythrocytes. The
      results are discussed in terms of a possible aggregation of the insecticide in
      the lipid bilayer to create special domains with a consequent increase in
      membrane instability.

PMID- 8535303
TI  - Molecular analysis of HLA genes for the selection of unrelated bone marrow donor.
AB  - The selection of fully matched unrelated volunteer donors (UVD) in BMT requires a
      molecular characterization of MHC polymorphism, since most phenotypically HLA
      identical donors can be non-identical when analyzed at a genomic level. The
      present report describes a molecular typing protocol for HLA genes developed for
      the selection of UVD, and its application to some donor-recipient pairs. The
      protocol involves three successive steps. Firstly, PCR with sequence-specific
      primers for HLA-DRB1 and -DQB1 genes is performed to identify the major alleles
      of the recipient. PCR-fingerprint matching is then introduced for HLA-A, B, C and
      DRB, DQB and DPB genes to screen prospective donors. Those showing matched
      fingerprinting patterns are finally submitted to direct sequencing of the DRB1
      gene. DPB compatibility is assessed by oligotyping when there are several
      potential class I and DRB matched donors. This strategy was applied
      retrospectively to three BMT recipients and their previously selected donors.
      Three other patients and their 12 prospective donors were submitted to our
      protocol before BMT. Clinical evaluation of transplant outcomes indicates the
      primary importance of complete DRB and class I matching, while DQB and DPB
      compatibility seems to be less critical.

PMID- 8535304
TI  - Suppression of normal and neoplastic human T cells with unconjugated monoclonal
      antibodies in SCID mouse chimeras.
AB  - The aim of this study was to establish a preclinical in vivo model to evaluate
      the suppressive effect of unconjugated anti-human T (CD3, 5, 7)-cell monoclonal
      antibodies (mAb) of mouse IgG2a or rat IgG2b isotype. Therefore, severe combined
      immunodeficient (SCID) mice were transplanted with human peripheral blood
      lymphocytes (PBL) of healthy donors (hu-PBL-SCID) or with neoplastic T cells of
      the human T-ALL cell line Jurkat. In preselected hu-PBL-SCID mice with
      substantial T cell chimerism single antibody injection caused prompt suppression
      of circulating human T lymphocytes within 2 days followed by occasional T cell
      recovery during the following weeks. Furthermore, antibody-mediated T cell
      suppression was measured by prolonged survival of SCID mice that had been
      injected with Jurkat cells preadapted to cause 100% mortality within 40 days.
      Injection of preadapted Jurkat cells caused fatal metastasis in lymphoid as well
      as non-lymphoid organs. The progression of leukemic cells was successfully
      suppressed when cells and anti-T cell mAb were given i.p. In contrast to control
      mice, tumor mortality of antibody-treated animals was delayed or completely
      suppressed. We conclude that SCID mice with reproducible human T cell chimerism
      are a relevant animal model to test the suppressive effect of anti-human T cell
      mAb in preclinical studies.

PMID- 8535305
TI  - Treatment of relapsing experimental autoimmune encephalomyelitis in rats with
      allogeneic bone marrow transplantation from a resistant strain.
AB  - We previously showed that relapsing experimental autoimmune encephalomyelitis (R
      EAE) in BUF rats, a model for multiple sclerosis, responds favorably to treatment
      with TBI and syngeneic BMT. Relapses of paresis occurred less frequently than in
      untreated controls, but were not completely prevented. Therefore, we investigated
      the effect of allogeneic BMT from the resistant WAG rat strain. BUF rats were
      treated with either high-dose TBI or CY and Bu followed by allogeneic BMT. This
      treatment induced complete remission, and reduced both the spontaneous and
      induced relapse rate more efficaciously than syngeneic BMT. Evidence is provided
      that a subclinical GVHR contributes to the prevention of spontaneous relapses.
      The almost complete absence of induced relapses likely results from the
      repopulation by the resistant immune system of the donor, which proved to be
      functional by responding to immunization with type II collagen. It is thus
      unlikely that a BMT-related immunodepression contributed to the lower incidence
      of induced relapses. We propose that allogeneic BMT should be considered for the
      treatment of severe progressive MS with a poor prognosis.

PMID- 8535306
TI  - Dose escalation study of high-dose carboplatin and etoposide with autologous bone
      marrow support in patients with recurrent and refractory germ cell tumors.
AB  - Thirty-three patients with germ cell cancer (GCT) recurrent after two cisplatin
      based regimens or cisplatin refractory (progression within 4 weeks of the last
      dose of cisplatin) were enrolled in a trial to establish the maximum tolerated
      doses (MTD) of carboplatin and etoposide given in combination with ABMT for two
      cycles. BM harvest of > or = 2 x 10(8) nucleated cells/kg preceded two cycles of
      therapy. Each agent was dose escalated, carboplatin from 1650 mg/m2 to 2100 mg/m2
      and etoposide from 1200 mg/m2 to 2250 mg/m2 per cycle in successive cohorts.
      Twenty patients completed two cycles, 13 underwent only one due to: early death
      (4), toxicity (2), and progressive disease (6). There were four CR, three of whom
      achieved NED status with surgery, 14 PR, of whom eight have progressed. Four
      patients with stable disease and seven PD have died with a median survival of 6
      months. There were six treatment-related deaths, four on course 1 and two on
      course 2. Causes of death on course 1 were: CNS hemorrhage (1), multiorgan
      failure (3); and on course 2: sepsis (1) and sudden death (1). Severe but
      reversible mucositis, transaminase and creatinine elevations were observed at the
      highest dose level. Three of five patients treated at this dose level had severe
      neurologic toxicity, manifested by both peripheral neuropathy and ototoxicity.
      The MTD in this patient population was carboplatin 2100 mg/m2 and etoposide 2250
      mg/m2 on each of two cycles of therapy. Neurologic and mucosal toxicity were dose
      limiting.

PMID- 8535307
TI  - Engraftment characteristics of peripheral blood stem cells mobilised with
      cyclophosphamide and the delayed addition of G-CSF.
AB  - The optimal protocol for the mobilisation of PBSC remains unknown. We present
      data on 42 patients mobilised with cyclophosphamide (3 or 4 g/m2) and the delayed
      addition of a standard 300 micrograms dose of G-CSF (Filgrastim) from day +5. The
      patients had received a median of 2 previous chemotherapy regimes, 38% had
      received prior radiotherapy and 38/42 had active disease at the time of
      mobilisation. The protocol was well tolerated and 38 patients proceeded to
      transplantation. The median number of CD34+ cells reinfused was 4.3 x 10(6)/kg
      (range 0.5-30) and CFU-GM 15.8 x 10(4)/kg (range 0-148). The total number of
      CD34+ cells harvested correlated with the total number of CFU-GM available for
      reinfusion (P = 0.008). Overall engraftment occurred within median days to
      neutrophils > 0.5 x 10(9)f/l or platelets > 20 x 10(9)/l of 14 and 13 days,
      respectively. Patients receiving more than 2.5 x 10(6)/kg CD34+ cells had even
      more rapid haemopoietic reconstitution with significant reductions in hospital
      stay and transfusion requirements. Those below this threshold had significantly
      delayed platelet engraftment. The mobilising dose of cyclophosphamide did not
      influence the achievement of the threshold CD34+ cell yield for optimal
      engraftment. The delayed addition of a standard 300 micrograms G-CSF dose after
      priming chemotherapy resulted in the use of a median 9 days hence 9 vials of G
      CSF. This protocol presents the potential for cost saving without compromising
      the quality or success of PBSC mobilisation.

PMID- 8535308
TI  - Interleukin-12 (IL-12) alone or in synergistic combination with IL-2 for in vitro
      activation of human bone marrow: differential effects at different time points.
AB  - IL-12 augments many effector functions associated with T and NK cells including
      induction of cytotoxic activity and secretion of various cytokines. In addition,
      synergistic responses with IL-2 in most of the functions attributed to that
      cytokine make IL-12 an attractive candidate to have a potential role as an
      immunotherapeutic agent. We have evaluated the effect of rhIL-12 either alone or
      in combination with IL-2 on the generation of cytotoxic effectors from normal
      human bone marrow. IL-12 induced cytotoxic effectors against NK sensitive targets
      within 24 h of stimulation and this activity was maintained in cultures with IL
      12 supplementation for up to 2 weeks tested. The decline in NK activity seen in
      control cultures over a period of 2 weeks was thus not observed in IL-12
      stimulated cultures. In addition, a small increase was also observed in cytotoxic
      activity against NK resistant Daudi cell targets. IL-12, when combined with a low
      to intermediate dose of IL-2, led to enhancement in IL-2 induced cytotoxicity
      against both NK sensitive and resistant targets. However an increase in
      cytotoxicity against NK resistant targets was evident only after 1 week of
      stimulation. Cellular yield and number of hematopoietic precursors (LTC-IC, CFU
      GM, BFU-e) in IL-12 stimulated cultures was comparable to or higher than control
      cultures at all the three time points (days 1, 7, 14) tested. In contrast,
      cultures stimulated with a combination of IL-12/IL-2 showed an increased number
      of hematopoietic precursors at day 1 followed by a marked decrease in the number
      of these precursors at day 7 and day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535309
TI  - Short-term in vivo priming of bone marrow haematopoiesis with rhG-CSF, rhGM-CSF
      or rhIL-3 before marrow harvest expands myelopoiesis but does not improve
      engraftment capability.
AB  - In an attempt to optimize bone marrow grafts for autologous transplantation 37
      sequential patients suffering from various haematological diseases were treated
      with either recombinant human granulocyte colony-stimulating factor (rhG-CSF) (n
      = 23) or granulocyte-macrophage CSF (rhGM-CSF) (n = 8) for 5 days or interleukin
      3 (rhIL-3) (n = 6) for 10 days before marrow harvest. All patients were in marrow
      remission at study entry. In contrast to rhIL-3, the administration of rhG-CSF or
      rhGM-CSF caused a significant (P < 0.01) increase in blood absolute neutrophil
      count. An increased marrow cellularity and a rise in the myeloid:-erythroid ratio
      was seen in the majority of patients during therapy, and in the rhIL-3 treated
      group a rise in the number of megakaryocytes and increased marrow fibrosis was
      seen in most patients. Moreover, a median of 2-, 5- and 10-fold increase in
      myeloid progenitors was the result of short-term administration of rhIL-3, rhGM
      CSF and rhG-CSF, respectively. However, transplantation performed with primed
      expanded marrow grafts did not significantly reduce the time to myeloid
      regeneration when compared to historical controls. In conclusion, the results
      demonstrate that short-term priming with haematopoietic cytokines before
      autologous bone marrow stem cell harvest is a safe procedure which effectively
      expands marrow haematopoisis without enhanced engraftment capability.

PMID- 8535310
TI  - Mismatched bone marrow transplantation for Omenn syndrome: a variant of severe
      combined immunodeficiency.
AB  - Omenn syndrome is a variant of SCID, inherited as an autosomal recessive
      disorder, and characterized by severe eczematoid dermatitis, eosinophilia,
      elevated serum IgE and a distinctive histology in enlarged lymph nodes. The
      etiology of Omenn syndrome is unknown, however, unlike other forms of SCID;
      patients with Omenn syndrome have activated T lymphocytes in their circulation
      capable of non-MHC restricted cytotoxic function. Recently, it has been observed
      that the use of immunosuppressive therapy, particularly cyclosporine, can modify
      the clinical manifestations of the disorder. Prior to the use of bone marrow
      transplantation this disease was universally fatal. Death typically occurred in
      infancy as the result of opportunistic infections and/or malignancies, most
      notably lymphomas. While bone marrow transplantation has become quite successful
      for many phenotypes of SCID, even with the use of alternative donors other than
      histocompatible siblings, in Omenn syndrome it remains a challenge. In our
      experience, patients with Omenn syndrome exhibit a higher incidence of Gram
      negative sepsis, before and during transplantation, and carry a significant risk
      of post-transplant rejection when compared with patients with other phenotypes of
      SCID. We report the results of six patients treated with bone marrow
      transplantation from alternative donors, three had unrelated donors (URD) and
      three had haplo-identical parental donors. Five of the six patients achieved
      complete and/or durable donor cell engraftment and only one patient experienced
      acute GVHD. Three patients died of transplant-related complications (infection or
      EBV-associated B cell lymphoma) between day +22 and day +95 post-transplant.
      Three patients survived more than 1 year post-transplant.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8535311
TI  - Autologous bone marrow transplantation for non-transformed low-grade non
      Hodgkin's lymphoma.
AB  - The purpose of this study was to evaluate autologous bone marrow transplantation
      (ABMT) for low-grade non-Hodgkin's lymphoma (NHL). Between 1983 and 1994, 34
      patients with non-transformed low-grade NHL received high-dose chemoradiotherapy
      plus stem cell rescue with marrow or peripheral blood. At transplantation (5-182
      months (median 32) after diagnosis), 2 patients were in complete remission (CR),
      21 in partial remission (PR) or minimal disease; 11 had bulky/resistant disease.
      Four patients died from transplant-related causes and 10 from lymphoma
      progression. After 40 months median follow-up, 20 survive between 3+ and 88+
      months after ABMT. One-year survival is 81% (95% confidence interval, 65-96%) and
      5-year survival 37% (14-60%). The probability of relapse at 1 and 2 years is 53%
      (34-72%) and 75% (54-96%), respectively. Twenty-nine patients were in CR
      following ABMT and 11 survive in continuous CR 3 to 54 months later. Disease-free
      survival at 1 and 2 years is 35% (19-52%) and 18% (2-31%). Resistant disease was
      the only factor significantly associated with poor overall (relative risk = 3.0,
      P = 0.04) and disease-free survival (RR = 5.4, P = 0.003), while resistant
      disease and high LDH were associated with increased relapse. ABMT yields a high
      CR rate for patients with progressive low-grade NHL, but relapse is frequent.
      Even longer follow-up is required to determine its effectiveness in extending
      survival of patients with pre-transplant responsive disease.

PMID- 8535312
TI  - Combination therapy with aerosolized ribavirin and intravenous immunoglobulin for
      respiratory syncytial virus disease in adult bone marrow transplant recipients.
AB  - Respiratory syncytial virus (RSV) infections in adult BMT recipients are
      frequently complicated by fatal pneumonias. Therapy of RSV pneumonia with
      aerosolized ribavirin alone has been reported to be associated with a 70%
      mortality rate. Because immune globulin therapy has been reported to be
      beneficial, we conducted a prospective trial of combination therapy with
      aerosolized ribavirin and intravenous immunoglobulin (IVIG). Aerosolized
      ribavirin was administered at 20 mg/ml for 18 h a day and IVIG was administered
      at 500 mg/kg every other day for the length of ribavirin therapy. Four lots of
      IVIG were chosen with RSV microneutralization Ab titers of 1:2048 to 1:8102.
      Between 8 January and 3 March 1993, during a community outbreak, 19 (45%) of 42
      hospitalized adult BMT recipients with an acute respiratory illness were
      documented to have RSV disease. Two-thirds of these infections were hospital
      acquired. All 19 patients presented with signs and symptoms of an upper
      respiratory tract illness. Sixteen patients developed pneumonia. The mortality
      was 22% in nine patients with pneumonia in whom therapy was initiated prior to
      the onset of profound respiratory failure. In contrast, the mortality was 100% in
      three patients with pneumonia in whom therapy was initiated within 24 h of
      respiratory failure requiring mechanical ventilation and in four untreated
      patients. We conclude that RSV may cause devastating outbreaks of severe
      pneumonia among hospitalized adult BMT recipients. Early diagnosis and
      combination therapy with ribavirin and IVIG was associated with a favorable
      outcome.

PMID- 8535313
TI  - Prophylactic ganciclovir is more effective in HLA-identical family member marrow
      transplant recipients than in more heavily immune-suppressed HLA-identical
      unrelated donor marrow transplant recipients. Australasian Bone Marrow Transplant
      Study Group.
AB  - A multi-centre Australasian study of the efficacy of prophylactic ganciclovir in
      88 recipients of marrow allografts at high risk for post-transplant
      cytomegalovirus (CMV) disease was conducted. The actuarial incidence of CMV
      disease was 10% in 74 recipients of HLA-identical family member transplants given
      ganciclovir but was 33% in 14 recipients of HLA-identical unrelated donor
      transplants given more immune-suppression pre- and post-transplant (P = 0.006).
      CMV disease developed in 4 of the 14 recipients of HLA-identical unrelated donor
      transplants at a median of 59 days post-transplant and was associated with
      concurrent graft-versus-host disease (GVHD) in 2 of the 4. CMV disease occurred
      in 5 of 74 recipients of an HLA-identical family member transplant at a median of
      137 days post-transplant and was associated with concurrent moderate to severe
      GVHD in 4 of the 5. Thus the risk of CMV disease was higher in recipients who
      were not genotypically identical for HLA with their donors and who (in
      consequence) were given more immune-suppression than HLA-identical family member
      transplant recipients. Additionally, CMV disease can occur beyond the period of
      prophylactic ganciclovir administration (first 3 months post-transplant) in
      patients developing significant chronic GVHD and prophylaxis should be
      reintroduced at that time in such patients.

PMID- 8535315
TI  - T cell reconstitution after bone marrow transplantation into adult patients does
      not resemble T cell development in early life.
AB  - Immune reconstitution after marrow transplantation has some characteristics of
      immune development in early life. Here we provide phenotypic data suggesting this
      may not be true for T cells (particularly CD4+ T cells) in the case of marrow
      transplantation into adults. T cells from 35 adult patients at 1 year after
      transplant, 14 normal neonates and 22 normal adults were studied by 3-color flow
      cytometry. Marked disparity between the phenotype of neonatal vs post-transplant
      T cells was found. Of the total CD4+ T cells, the neonates had supranormal
      percentages of CD45RAhigh, L-selectin+, CD29low/-, CD11alow/- and CD28+ cells
      whereas most patients at 1 year after transplant had subnormal percentages of
      these CD4+ T cell subpopulations. (sub/supra-normal denotes below/above normal
      adult values). Absolute blood counts of naive (CD45RAhigh, L-selectin+, CD29low/-
      and CD11alow/-) CD4+ T cells correlated inversely with patient age. Neonates had
      also supranormal percentages of CD45RAhigh, L-selectin+, CD29low/-, CD11alow/-
      and CD28+ CD8+ T cells whereas the patients (particularly those with chronic
      GVHD) tended to have subnormal percentages of these CD8+ T cell subpopulations.
      Contrary to the CD4+ T cells, there was no correlation between the absolute
      counts of CD45RAhigh, L-selectin+, CD29low/- or CD11alow/- CD8+ T cells and
      patient age. Whereas the vast majority of neonatal T cells were CD38high, most
      patient and normal adult T cells were CD38- or CD38intermediate (both CD4+ and
      CD8+ T cells). We conclude that, in contrast to early life, the production of
      naive CD4+ T cells is deficient in adult (and particularly elderly) transplant
      recipients.

PMID- 8535314
TI  - Hepatitis C virus infection and liver failure in patients undergoing allogeneic
      bone marrow transplantation.
AB  - The role of hepatitis C virus (HCV) infection in severe liver failure (LF)
      following bone marrow transplantation is still uncertain. We therefore decided to
      determine the presence of HCV-RNA in 31 patients who died of severe LF after BMT
      and in 26 matched BMT controls who did not develop LF. HCV-RNA was identified by
      polymerase chain reaction and anti-HCV by second generation enzyme-linked
      immunoassay and by 4-band recombinant immunoblotting assay in serum samples
      obtained before and after BMT. Biochemical and clinical parameters of liver
      disease were obtained by reviewing clinical records. LF developed at a median
      interval of 80 days (20-570) from transplantation and was clinically assessed as
      VOD (n = 7), liver GVHD (n = 5) or hepatitis (n = 19). HCV-RNA was detected,
      respectively, in 15/31 (48%) and in 12/26 (46%) of LF patients and controls (P =
      0.9). Conversely, the risk of dying of LF was 62% and 53% (P = 0.5) respectively,
      for HCV-RNA positive and negative patients. Anti-HCV profile did not correlate
      with viremia, nor with type of liver disease. These findings indicate that,
      despite a 47% prevalence of HCV infection in our series, HCV-RNA positivity was
      neither a predictor of VOD nor a marker for life-threatening liver disease.

PMID- 8535316
TI  - Alterations of T cell repertoire after bone marrow transplantation:
      characterization of over-represented subsets.
AB  - We recently demonstrated that frequencies of T cell receptor-V (TcR-V)-specific
      subsets are frequently altered after both allogeneic and autologous BMT. The data
      reported here describe several characteristics of altered T cell subsets: (i)
      their capacity to endure peripherally, (ii) their correspondence to clonal donor
      T cell subsets, (iii) the origin of the clone (in one case amenable to analysis)
      from a mature T cell and not from new lymphopoiesis, and (iv) the presence of
      such a clone throughout a year of follow-up in a patient with chronic graft
      versus-host disease (GVHD) in whom it represented up to 1/10th of CD3+ peripheral
      blood lymphocytes (PBL) and was found to be host-reactive. Taken together, these
      findings provide direct evidence for the oligoclonality of a large proportion of
      the peripheral T cell repertoire in patients subsequent to bone marrow
      transplantation, possibly accounting for their frequent depressed immune status.
      Moreover, the anti-host reactivity demonstrated in a clone from the patient with
      chronic GVHD strongly suggests that an oligoclonal response can be linked to a
      pathological process.

PMID- 8535317
TI  - Detection of minimal residual disease in patients with childhood common acute
      lymphoblastic leukemia after autologous bone marrow transplantation with ex vivo
      purging and systemic IL-2 infusion: unsuccessful prediction of subsequent
      relapse.
AB  - We sequentially analyzed minimal residual disease (MRD) in 7 children with common
      acute lymphoblastic leukemia (cALL) after autologous bone marrow transplantation
      (ABMT) with ex vivo purging followed by systemic interleukin-2 infusion. After
      ABMT, 3 of the 7 patients remained in complete remission (CR) for more than 1
      year, and 4 subsequently relapsed. MRD was estimated by polymerase chain reaction
      amplification to detect the leukemia clone-specific immunoglobulin heavy chain
      third complementarity determining region (IgH CDR-III). The IgH CDR-III sequences
      from the relapsed patients were identical with those determined at each
      respective initial diagnosis. In 2 patients, the levels of MRD were 10(-2) and
      10(-5) in the harvested bone marrow (BM) cells, and even after purging the levels
      were 10(-4) and 10(-5) cells, respectively. One of the 2 patients relapsed 3
      months after ABMT, while the other remained in CR for 33 months after ABMT. Among
      the 4 patients who subsequently relapsed after ABMT, MRD was not detected in the
      BM samples even 1 month before relapse. Our results suggest that PCR-negativity
      does not necessarily indicate a lower risk of subsequent relapse. Detection of
      MRD tends to favor the assessment of the therapeutic effects rather than
      prediction of relapse.

PMID- 8535318
TI  - Allogeneic mouse T cell lines distinguish three Balb/c leukemias from each other
      and from non-leukemic lymphocytes.
AB  - In order to separate graft-versus-leukemia (GVL) effect from graft-versus-host
      (GVH) reactions in allogeneic cell therapy, we established cytotoxic T cell lines
      (CTL) against irradiated A20, WEHI-3 and PU cells, ie cells from 3 hematopoietic
      tumors of Balb/c origin. Immunization with these cell lines did not lead to
      prolonged survival in Balb/c mice. The cytotoxic activity of the CTL was tested
      against the 3 leukemias. In all 9 combinations the highest specific lysis was
      achieved against the stimulating tumor. Cold target inhibition experiments showed
      that the activity against 51Cr-labelled leukemia cells could be almost completely
      inhibited by adding a sufficient amount of unlabelled target cells. On the other
      hand, when unlabelled concanavalin A-induced Balb/c blast cells were added, the
      inhibition was incomplete. By means of flow cytometry it was excluded that the
      different susceptibilities and inhibitory potentials of tumor cells and
      nonmalignant blasts are caused solely by differences in the MHC expression of the
      target cells. These findings confirm that allogeneic CTL are capable of
      discriminating malignant from nonmalignant cells, even if the tumor is
      nonimmunogenic in syngeneic animals.

PMID- 8535319
TI  - Evidence for a possible role of Asialo-GM1-positive cells in the graft-versus
      leukemia repression of a murine type-C retroviral leukemia.
AB  - Studies were performed to examine whether, in addition to T cells, there might be
      other immune cells also capable of exerting a graft-versus-leukemia (GVL)
      response following allogeneic marrow transplant. Using an MHC-matched mouse
      model, consisting of normal B10.S donors and SJL/J Rauscher-retroviral-leukemic
      recipients, the donor cells were selectively depleted of their Asialo-GM1+
      component prior to being infused into the leukemic recipients. The incidence of
      relapse was then compared against that for matched leukemic control recipients of
      undepleted cells from the same donors. FCM analysis of the depletion protocol
      indicated that exposure to anti-Asialo-GM1 antibody eliminated more than half of
      the donor NK1.1+ cells, but caused no significant losses among the Thy-1+, CD3+,
      or CD8+ cells. Nevertheless, fatal relapse among the leukemic recipients of the
      depleted cells was nearly double that found among the leukemic control recipients
      of undepleted cells, 47.5 vs 25.4% (P = 0.01). In a parallel study, using normal
      SJL/J recipients, this same depletion protocol was found to have no significant
      effect on the incidence of graft-versus-host disease (GVHD). These results
      therefore suggest that Asialo-GM1+ NK cells may be capable of contributing to the
      suppression of relapse in this type of leukemic recipient of allogeneic marrow,
      and that this suppression may occur independently of GVHD.

PMID- 8535320
TI  - The role of antibodies to IL-2 receptor and Asialo GM1 on graft-versus-leukemia
      effects induced by bone marrow allografts in murine B cell leukemia.
AB  - The role of various cell subpopulations involved in the graft-versus-leukemia
      (GVL) effect induced by allogeneic bone marrow transplantation (BMT) was
      investigated in (BALB/c x C57BL/6)F1 (F1) recipients, inoculated with murine B
      cell leukemia (BCL1), by using monoclonal murine anti-IL-2 receptor antibodies or
      rabbit anti-Asialo GM1 antibodies directed predominantly against murine NK cells.
      F1 mice with BCL1 were irradiated and reconstituted with parental (C57BL/6) bone
      marrow cells (BMC) or a mixture of BMC and spleen cells and treated in vivo for
      10 days with anti-IL-2 receptor antibody or anti-Asialo-GM1 antibody. Both
      treatments lessened the GVL effects induced by the allograft and resulted in
      development of leukemia relapse, as documented in vivo by adoptive transfer of
      10(5) spleen cells obtained from treated mice into secondary syngeneic adoptive
      recipients. Our data indicate that IL-2 receptor-positive T cells and possibly IL
      2-activated allogeneic NK cells play a key role in inducing GVL following
      allogeneic BMT.

PMID- 8535322
TI  - Pure red cell aplasia complicating an ABO-compatible allogeneic bone marrow
      transplantation, treated successfully with antithymocyte globulin.
AB  - A patient underwent an HLA-identical ABO-compatible allogeneic bone marrow
      transplant for aplastic anemia. She then developed pure red cell aplasia which
      was treated successfully with antithymocyte globulin and methylprednisolone,
      after failing to respond to intravenous immune globulin infusion.

PMID- 8535321
TI  - Cost-effectiveness of ABMT in comparison with CHOP chemotherapy in patients with
      intermediate- and high-grade malignant non-Hodgkin's lymphoma (NHL).
AB  - A prospective randomized clinical trial with simultaneous data collection for an
      economic appraisal was carried out to assess the effectiveness, quality of life
      and cost implications of ABMT vs standard chemotherapy in slowly responding
      patients with intermediate- and high-grade malignant non-Hodgkin's lymphoma
      (NHL). The patients had a partial response after three cycles of chemotherapy and
      had no evidence of BM involvement of NHL. The overall and disease-free survival
      at 3 years were 61% and 60%, respectively, in the ABMT group and 85% and 77% in
      the CHOP group (P = NS). Moreover, there were more (severe) complications and
      symptoms in the ABMT than in the CHOP group. The average costs of CHOP
      chemotherapy were significantly lower than the average costs in the ABMT group
      (CHOP: US$ 3118 vs ABMT: US$ 34,447). Considering long-term consequences the ABMT
      group was more expensive (US$ 34,580) and patients experienced 0.14 life years
      and 0.22 quality adjusted life years less than the CHOP group (discount rate 5%).
      As a result, changing therapy from CHOP to ABMT, as primary treatment in slow
      responders to CHOP, can not be recommended as the required additional investment
      does not produce health gains in terms of survival or quality of life.

PMID- 8535323
TI  - Allogeneic liver transplantation for hepatic veno-occlusive disease after bone
      marrow transplantation--clinical and immunological considerations.
AB  - Veno-occlusive disease (VOD) is a frequent complication early after bone marrow
      transplantation. In cases of severe liver failure treatment by allogeneic liver
      transplantation is possible. We report the clinical and immunological course of a
      patient after bone marrow transplantation for AML and subsequent allogeneic liver
      transplantation for severe hepatic VOD. After liver transplantation the patient
      recovered well clinically. Early after liver transplantation he had large numbers
      of liver donor T and NK lymphocytes in his circulation. He had no liver graft
      rejection, but he developed mild acute GVHD which was caused by liver graft
      derived T lymphocytes. Two years after transplantation he had persistent
      microchimerism with donor liver cells detectable in his bone marrow. Now 36
      months after transplantation, the patient has no evidence of recurrent leukemia,
      stable liver function, and no signs of graft-versus-host disease or bone marrow
      dysfunction.

PMID- 8535324
TI  - Remission of a lymphoproliferative disorder occurring after second BMT from an
      unrelated donor in a 5-year-old boy with severe aplastic anemia.
AB  - A 5-year-old boy with severe aplastic anemia failed to respond to cyclosporine
      (CYA), prednisolone and antilymphocyte globulin (ALG). No suitable sibling marrow
      donor was available, but an HLA-matched unrelated donor was identified. The
      patient was conditioned with cyclophosphamide (CY), 50 mg/kg/day for 4 days,
      total nodal irradiation (8 Gy), and ALG 30 mg/kg/day for 3 days. GVHD prophylaxis
      consisted of daily CYA, methotrexate (MTX) and ALG. The patient failed to achieve
      sustained engraftment. He was reconditioned with high-dose prednisolone and anti
      T lymphocyte monoclonal antibody OKT3. The boy was reinfused with the same donor
      marrow on day 0 (+49/first BMT). No GVHD prophylaxis was given the second time.
      He received G-CSF on days 0 to +20 after the second transplant. Full engraftment
      was achieved on day +16 (+65). However, on day +31 (80) he developed a biopsy
      proven B cell lymphoproliferative disorder (BLPD). After the OKT3 administration
      was stopped and treatment with ganciclovir and high-dose immunoglobulin was
      initiated, the BLPD resolved and the patient was discharged on day +50 (99). He
      is currently well with a functioning graft 266 (305) days posttransplant, with no
      sign of GVHD.

PMID- 8535325
TI  - Chemotherapy and recombinant human granulocyte colony-stimulating factor primed
      donor leukocyte infusion for treatment of relapse after allogeneic bone marrow
      transplantation.
AB  - Two patients affected by acute leukemia relapsed 10 and 12 months respectively
      after allogeneic bone marrow transplantation. They were treated with aggressive
      chemotherapy and then infused with HLA-identical donor leukocytes (DLI) collected
      after recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      administration. A total of 5.6 and 6.3 x 10(6)/kg CD34+ cells, 2.7 and 3.0 x
      10(4)/kg CFU-GM, 4.7 and 4.4 x 10(8)/kg MNC, 4.6 and 3.9 x 10(9)/kg PMN
      respectively were infused. Both patients achieved complete remission (CR) and
      complete chimerism was re-established. One patient developed grade IV acute graft
      versus-host disease of the liver requiring immunosuppression and he died in CR
      from disseminated aspergillosis, 7 months after chemotherapy; one patient is
      alive in relapse 12 months after treatment.

PMID- 8535326
TI  - Donor buffy coat infusions for a patient with myelodysplastic syndrome who
      relapsed following allogeneic bone marrow transplantation.
AB  - A 49-year-old man with myelodysplastic syndrome (MDS, RAEB in T) who relapsed
      following allogeneic bone marrow transplantation (allo BMT) was treated with
      infusions of donor buffy coat leukocytes. He sustained hematologic and
      cytogenetic remission, but severe graft-versus-host disease (GVHD) developed for
      which cyclosporin A and prednisolone were required. This therapeutic approach
      appears to be valuable for relapsed MDS following allo BMT as well as for chronic
      myelogenous leukemia (CML).

PMID- 8535327
TI  - Successful bone marrow transplantation in patients with recent Pneumocystis
      carinii pneumonia: report of two cases.

PMID- 8535328
TI  - Secondary cancer after syngeneic bone marrow transplant.

PMID- 8535329
TI  - Biodistribution and radioimmunopharmacokinetics of 131I-Ama monoclonal antibody
      in atherosclerotic rabbits.
AB  - Monoclonal antibodies have been raised against Ama isolated from human and
      experimental atherosclerotic plaque. 131I-Ama-MoAb in the whole antibody form was
      injected into normal NZW rabbits and Watanabe hyperlipidemic rabbits.
      Biodistribution studies showed that atheromatous aortas had a significantly
      higher (5-7X) uptake of 131I-Ama-MoAb than that of normal aortas. However, 131I
      Ama-MoAb was cleared very slowly from atherosclerotic rabbits. As a result,
      atheromas could not be identified by imaging because of the low target to non
      target ratios.

PMID- 8535330
TI  - Propionyl-L-carnitine: labelling in the N-methyl position with carbon-11 and
      pharmacokinetic studies in rats.
AB  - The prospective therapeutic, propionyl-L-carnitine, was labelled in the N-methyl
      position with the positron-emitter, carbon-11 (t1/2 = 20.4 min), with a view to
      studying its pharmacokinetics in humans using PET. Labelling was achieved by
      methylating nor-propionyl-L-carnitine hydrochloride with no-carrier-added
      [11C]iodomethane (produced from cyclotron-produced [11C]carbon dioxide) in
      ethanol in the presence of 1,2,2,6,6-pentamethylpiperidine. HPLC of the reaction
      mixture on a strong cation exchange column provided high purity [N-methyl
      11C]propionyl-L-carnitine in 62% radiochemical yield (decay-corrected from
      [11C]iodomethane), ready for intravenous administration within 35 min from the
      end of radionuclide production. [N-methyl-11C]Propionyl-L-carnitine, given
      intravenously to rats, cleared rapidly from plasma. A slow uptake of
      radioactivity into myocardium and striated muscle was observed. In plasma,
      unchanged tracer represented 84% of the radioactivity at 2.5 min and 2.5% of the
      radioactivity at 60 min. In heart, unchanged tracer represented 18% of
      radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity
      detected in plasma and heart was identified as [N-methyl-11C]L-carnitine and [N
      methyl-11C]acetyl-L-carnitine.

PMID- 8535331
TI  - Synthesis and binding properties of [3H]NNC 12-0781, a new radioligand for the
      dopamine reuptake system.
AB  - The tritiated dopamine reuptake inhibitor [3H]NNC 12-0781 ([1-[2-(bis(4
      fluorophenyl)-methoxy)-ethyl]-4-(3-(2-furanyl)-2,3-[3H] - propyl)-piperazine) was
      radiolabelled in one step starting from 1-[2-(bis(4-fluorophenyl)-methoxy)-ethyl]
      4-(3-(2-furanyl)-2-propenyl)- piperazine, using tritium gas and PdO as catalyst.
      The radiochemical purity of [3H]NNC 12-0781 was higher than 99% after HPLC
      purification with a specific radioactivity of 21 Ci/mmol. [3H]NNC 12-0781 bound
      specifically to rat striatum in vitro at +4 degrees C with a Kd of 1.76 nM and
      Bmax of 587 fmol/mg tissue. The nonspecific binding was about 10% at Kd. At +37
      degrees C no acceptable binding was observed. The association of [3H]NNC 12-0781
      thus has the characteristics of a radioligand for the dopamine transporter in
      vitro at +4 degrees C.

PMID- 8535332
TI  - Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-D
      fructose.
AB  - Fluorine-18 labeled analog of D-fructose, 1-deoxy-1-[18F]fluoro-D- fructose (1
      [18F]FDFrc), was synthesized by nucleophilic substitution of [18F]fluoride ion
      and the effect of the fluorine substitution on its in vivo metabolism was
      investigated. The tissue distributions of 1-[18F]FDFrc in rats and tumor bearing
      mice showed initial high uptake and subsequent rapid washout of the radioactivity
      in the principal sites of D-fructose metabolism (kidneys, liver and small
      intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and
      moderate, respectively, but tended to increase with time. The in vivo metabolic
      studies of 1-[18F]FDFrc and nonradioactive 1-FDFrc in mouse brain and tumor
      showed that the fluorinated analog remained unmetabolized in these tissues,
      indicating that the substitution of fluorine at the C-1 position produces a
      nonmetabolizable analog of D-fructose. Thus, 1-[18F]FDFrc had no features of a
      metabolic trapping tracer without showing any appreciable organ or tumor specific
      localization.

PMID- 8535333
TI  - Iododerivative of pargyline: a potential tracer for the exploration of monoamine
      oxidase sites by SPECT.
AB  - Monoamine oxidases are important in the regulation of monoaminergic
      neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed
      in some neurodegenerative diseases, and therefore quantification of cerebral MAO
      B activity by SPECT would be useful for the diagnosis and therapeutic follow-up
      of these disorders. We have developed an iodinated derivative of pargyline, a
      selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable
      bromo and iodo derivatives of pargyline were synthesized and chemically
      characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with
      high specific activity from the bromo precursor by nucleophilic exchange.
      Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution
      study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were
      obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro
      affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B
      was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic
      studies and in vivo saturation studies with selective inhibitors of MAO showed
      that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is
      consistent with high level binding to MAO B sites in the pineal gland and in the
      thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B
      sites with high affinity. However, its selectivity for MAO B in rats is not very
      high, whereas this ligand binds to a lesser extent to MAO A. It will be then of
      great value to evaluate the specificity of 2-iodopargyline in humans. This new
      ligand labeled with 123I should therefore be a suitable tool for SPECT
      exploration of MAO B in the human brain.

PMID- 8535334
TI  - Synthesis, radiolabeling, and preliminary evaluation in mice of some (N
      diethylaminoethyl)-4-iodobenzamide derivatives as melanoma imaging agents.
AB  - N-(2-Diethylaminoethyl)-4-iodobenzamide (BZA) is a radiopharmaceutical recently
      developed in our laboratory for the scintigraphic detection of melanoma and
      metastases. Optimal time for imaging was between 18-24 h p.i. of [123I] BZA. With
      a view to selecting compounds able to provide quality images shortly after the
      injection, synthesis of an initial series of BZA derivatives and their evaluation
      in B16 melanoma bearing mice have been carried out. The [125I] radiolabeled
      products were obtained by a simple isotopic exchange procedure with high
      radiochemical yields (85-95%). After i.v. administration of the compounds we
      observed a good tumoral targeting ability. Tumoral activity peaked at 2.6 to
      7.70% injected dose per g within 1 h post-injection. One of the benzamides with a
      blood clearance faster than that of BZA--0.06 vs. 0.2% I D/g--6 h p.i. gave the
      same tumor to blood and to organ ratios as BZA at 12-18 h p.i. Based on these
      preclinical data we hope to obtain good tumoral images 6 h p.i. in scintigraphic
      studies in man.

PMID- 8535335
TI  - New bisaminoethanethiol (BAT) ligands which form two interconvertible Tc-99m
      complexes.
AB  - Most commonly used radiopharmaceuticals in diagnostic nuclear medicine are
      labeled with Tc-99m. This is due to its superior physical characteristics (T1/2 =
      6 h and gamma energy 140 KeV) and convenient availability from the 99Mo/99mTc
      generator. In an attempt to fine tune the properties of Tc-99m complexes, the
      synthesis and radiolabeling of two novel N2S2 ligands, N,-2-mercaptobenzyl-N'-(1
      oxo-2-mercapto-2-methyl)propyl ethylene-diamine, 8, and N,-2-methylthiobenzyl-N'
      (1-oxo-2-mercapto-2-methyl)propyl ethylenediamine, 11, with an ionizable SH or
      unionizable SMe group, respectively, for the formation of complexes with TcvO
      center cores, have been examined. Both ligands initially formed one apparently
      stable, lipophilic and neutral complex (HPLC, Rt = 7 min, reverse-phase column,
      acetonitrile: buffer, pH 7.0; 55/45; V/V; partition coefficient between 1-octanol
      and buffer of 410 and 335, respectively) with [99mTc]pertechnetate in the
      presence of stannous chloride. After treatment with a reducing agent, NaCNBH3,
      the initial [99mTc]8 and 11 complexes were reduced; the reduced complexes were
      less lipophilic (shorter retention time, Rt = 5 min, on the same reversed phase
      HPLC). However, only the oxidized form showed sufficient stability. The reduced
      forms of both [99mTc]8 and 11 were readily and completely converted back to the
      oxidized forms by a stream of air. Biodistribution studies in rats demonstrated
      that the [99mTc]8 (oxidized form) penetrated the blood-brain barrier (0.67%
      dose/organ at 2 min postinjection), but washed out from the brain quickly (0.29%
      dose/organ at 30 min postinjection).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535336
TI  - Fluorine-18 labeled chemotactic peptides: a potential approach for the PET
      imaging of bacterial infection.
AB  - A potent chemotactic peptide, formyl-norleucyl-leucyl-phenylalanyl-norleucyl
      tyrosyl-lysine was derivatized by reaction with N-succinimidyl 4-fluorobenzoate.
      This derivatized peptide bound to human polymorphonuclear leukocytes in vitro and
      exhibited biological activity in a superoxide production assay. Peptide labeling
      using N-succinimidyl 4-[18F]fluorobenzoate was accomplished in reasonable yields
      with 10-15 mCi of labeled peptide available per 100 Ci of [18F]fluoride. With the
      exception of the gastrointestinal tract, clearance of activity from tissues
      following injection of this peptide in normal mice was rapid. Although
      preliminary in nature, these results suggest that 18F-labeled chemotactic
      peptides should be investigated as potential agents for positron emission
      tomographic imaging of bacterial infections.

PMID- 8535337
TI  - Cloning and sequencing of V genes from anti-osteosarcoma monoclonal antibodies TP
      1 and TP-3: location of lysine residues and implications for radiolabeling.
AB  - Monoclonal antibodies TP-1 and TP-3 are of potential utility for the
      radioimmunodiagnosis of osteosarcoma in both human and canine patients. The V
      genes of these antibodies were cloned and sequenced and to facilitate
      radiolabeling of these proteins, the location of the lysine residues within these
      sequences have been determined. The V-domains of TP-1 contain a total of 12
      lysines, 10 in the framework region and 2 in the CDR region, while the V-domains
      of TP-3 contain a total of 14 lysines, 11 in the framework region and 3 in the
      CDR regions. Using space-filling models, the availability of each lysine residue
      for radiolabeling, and potential interference with antigen binding was predicted.

PMID- 8535338
TI  - Evaluation of stereoisomers of 4-fluoroalkyl analogues of 3-quinuclidinyl
      benzilate in in vivo competition studies for the M1, M2, and M3 muscarinic
      receptor subtypes in brain.
AB  - To develop a subtype selective muscarinic acetylcholine receptor (mAChR)
      antagonist for PET, fluorine-19 labeled alkyl analogues of quinuclidinyl
      benzilate (QNB) were synthesized by stereoselective reactions. To investigate
      these analogues for tissue subtype specificity, in vivo competitive binding
      studies were performed in rat brain using (R)-3-quinuclidinyl (R)-4
      [125I]iodobenzilate (IQNB). Five, fifty, or five-hundred nmol of the non
      radioactive ligands were coinjected intravenously with 8 pmol of the radioligand,
      Cold (R,R)-IQNB blocked (R,R)-[125I]IQNB in a dose-dependent manner, without
      showing regional specificity. For the (R,S)-fluoromethyl, -fluoroethyl and 
      fluoropropyl derivatives, a higher percent blockade was seen at 5 and 50 mmol
      levels in M2 predominant tissues (medulla, pons, and cerebellum) than in M1
      predominant tissues (cortex, striatum and hippocampus). The blockade pattern of
      the radioligand also correlated qualitatively with the percentage of M2 receptors
      in the region. The S-quinuclidinyl analogues showed M2 selectivity but less
      efficient blockade of the radioligand, indicating lower affinities. Radioligand
      bound to the medulla was inversely correlated to the M2 relative binding affinity
      of the fluoroalkyl analogues. These results indicate that the nonradioactive
      ligand blocks the radioligand based on the affinity of the nonradioactive ligand
      for a particular receptor subtype compared to the affinity of the radioligand for
      the same receptor subtype. Of the seven compounds evaluated, (R,S)-fluoromethyl
      QNB appears to show the most selectivity for the M2 subtypes in competition
      studies in vivo.

PMID- 8535339
TI  - Synthesis of 2'-fluoro-5-[11C]-methyl-1-beta-D-arabinofuranosyluracil ([11C]
      FMAU): a potential nucleoside analog for in vivo study of cellular proliferation
      with PET.
AB  - Rapid in vivo catabolism limits the use of currently available radiotracers used
      in tumor proliferation studies with PET. This is manifested by the need to
      develop complex mathematical models to interpret kinetic and metabolite data
      obtained from imaging studies with agents such as carbon-11 labeled thymidine. A
      potential carbon-11 labeled radiotracer for cellular proliferation, 2'-fluoro-5
      ([11C]-methyl)-1-beta-D-arabinofuranosyluracil (FMAU), has been prepared using a
      previously described method for preparation of [11C]methyl-thymidine where
      selective alkylation of a pyrimidyl dianion is accomplished with [11C]methyl
      iodide at the 5-position of the pyrimidine ring. FMAU shares many in vivo
      characteristics of thymidine, including cellular transport, phosphorylation by
      mammalian kinase, and incorporation into DNA. Most importantly, in vivo
      catabolism of FMAU is limited, potentially yielding simplified kinetic models for
      determination of cellular proliferation with positron emission tomography.

PMID- 8535340
TI  - Selective alkylation of pyrimidyl dianions III: no-carrier-added synthesis of
      [11C-methyl]-thymidine.
AB  - A no-carrier-added, high specific activity synthesis of [11C-methyl]-thymidine is
      reported. Reaction of 3'. 5'-O-bis-(tetrahydropyramyl)-5-bromo-2'-deoxyuridine
      with n-butylithium produced a diamion which was alkylated with [11C]-methyl
      iodide, and on subsequent hydrolysis, yielded [IIC-methyl]-thymidine. The labeled
      compound was isolated from the by-product 2'-deoxymidine by HPLC on a reverse
      phase C18 semipreparative column with mean radiochemical yield of 18.8% (decay
      corrected) in 30-35 min and radiochemical purity >99%. This no-carrier-added
      synthesis can be used to produce [11C-methyl]-thymidine with mean specific
      activity over 1000 mCi/mumol for positron emission tomography (PET) studies.

PMID- 8535341
TI  - Direct 99mTc labeling of human immunoglobulin with an insoluble macromolecular
      Sn(II) complex.
AB  - An insoluble macromolecular Sn(II)(R-Sn) complex which strongly binds Sn(II) by
      chelation was applied to the direct 99mTc labeling of human immunoglobulin(IgG)
      to minimize the influence of Sn(II). 99mTc labeling was achieved at greater than
      90% yield simply by the short-term mixing of IgGa containing > 2-SH groups per
      IgG molecule, 99mTc pertechnetate, and the R-Sn complex in pH 7 solution. The
      99mTc-IgGa obtained by this labeling method has high stability based on the thiol
      specific binding of 99mTc without transchelation from another weakly bound 99mTc
      complex.

PMID- 8535342
TI  - Positron emission tomography (PET) study of the alterations in brain distribution
      of [11C]methamphetamine in methamphetamine sensitized dog.
AB  - [11C]Methamphetamine ([11C]MAP) was synthesized by an automated on-line
      [11C]methylation system for positron emission tomography (PET) study. We newly
      produced a MAP sensitized dog by repeated MAP treatment and studied the brain
      distribution of [11C]MAP in the normal and the MAP sensitized dog. The maximal
      level of accumulation of [11C]MAP in the sensitized dog brain was 1.4 times
      higher than that in the control. No difference was found in the metabolism of MAP
      between the two conditions. The significant increase of [11C]MAP in the MAP
      sensitized brain indicates that subchronic MAP administration causes some
      functional change in uptake site of MAP.

PMID- 8535343
TI  - Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET
      evaluation of an improved 18F-labeled ligand.
AB  - [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2
      antagonist benperidol, was evaluated as a radiopharmaceutical for use with
      positron emission tomography (PET). PET imaging of baboons after i.v. injection
      of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo
      within dopaminergic receptor-rich cerebral tissues, and that selective
      disposition was retained for over 2 h. Pretreatment of an animal with unlabeled
      receptor-specific antagonists prior to injection of [18F]BP confirmed that the
      radioligand bound specifically to central D2 receptors in vivo, and not to S2 or
      D1 receptors. [18F]BP bound to D2 receptors in a reversible manner; unlabeled
      eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was
      metabolized in the periphery to polar metabolites which are not expected to cross
      the blood-brain barrier. [18F]BP has advantages over other tracers as a
      radiopharmaceutical for PET study of central D2 receptor activity, and can be
      applied for noninvasive evaluation of the interaction of unlabeled drugs with
      central D2 receptor sites.

PMID- 8535344
TI  - Fate of mouse macrophages radiolabelled with PKH-95 and injected intravenously.
AB  - Mouse macrophages purified by elutriation from thioglycollate-induced peritoneal
      exudate cells were labelled with indium-111-oxine and injected intravenously into
      mice. A substantial amount of unbound radioactivity remained in the circulation,
      suggesting that the radionuclide was not stably bound to the cells. Culture
      experiments with radiolabelled cells showed that indium-111 was released in the
      medium. Another cell marker, PKH-95, an iodine-125-labelled aliphatic compound
      insertable into the cell membrane, bound more stably than indium-111. Five
      minutes after injection of 125I-PKH-95-labelled macrophages, about 98% of the
      cells were in a non-circulating pool. It was checked that PKH-95 labelling did
      not compromise the viability and functions of the macrophages and that autologous
      erythrocytes and blood mononuclear cells labelled with PKH-95 remained in the
      circulation after i.v. injection. One hour after injection, 125I-PKH-95-labelled
      macrophages were distributed mainly in lung (36%), liver (19%) and spleen (5%).
      Subsequently, radioactivity decreased in the lung while increasing in liver,
      spleen and in an artificially induced footpad inflammation. The radioactivity
      accumulation in the inflammation persisted at least for 7 days. It represented a
      small proportion of radioactivity injected (0.2%) but was trapped very
      specifically in the inflammation. This raised the hypothesis that macrophages of
      the non-circulating pool could be released in the circulation and recruited into
      the inflammation with slow kinetics.

PMID- 8535345
TI  - In vivo characterization of radioiodinated 2-(4-phenylpiperidino)cyclohexanol
      (vesamicol) analogs: potential radioligand for mapping presynaptic cholinergic
      neurons.
AB  - Iodovesamicol analogs, radioiodinated at the ortho (1), meta(2) and para(3)
      positions of the 4-phenylpiperidine moiety, were evaluated as potential
      presynaptic cholinergic neuron mapping agents. Significant accumulation of m
      [125I]iodovesamicol (mIV(2)) (about 3% of the injected dose) was noted in the rat
      brain with prolonged retention times. The accumulation of mIV(2) in the rat brain
      was decreased by 67% by 5 min pre-injection of dl-vesamicol(1 mumol/kg). Pre
      injection of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperdine[(+)-3-PPP](0.75
      mumol/kg) did not markedly decrease the levels of radiotracers (oIV(1) and
      mIV(2)) in the rat brain. These results suggest that radioidinated m
      iodovesamicol (mIV(2)) is suitable for use in presynaptic cholinergic neuron
      mapping.

PMID- 8535346
TI  - The influence of "selenium organicum" upon the hepatic function of carbon
      tetrachloride poisoned rats.
AB  - The hepatoprotective action of the Romanian preparation Orgasel containing
      selenium (Se) 5.01 mg/100 g autolysated yeast powder, was tested on adult Wistar
      rats poisoned with carbon tetrachloride (CCl4). The hepatotoxic agent (a 20% CCl4
      solution in oil) was administered i.p. in a single dose of 0.3 ml CCl4
      solution/100 g body weight, and the preparation tested (autolysate of seleniated
      yeast) was administered by gavage in 4 doses (of 100 mg Se powder/100 g animal
      each) along 2 days. After 48 hrs the animals were sacrificed, then their blood
      and liver were collected. The treatment with Orgasel significantly reduced the
      organs, morphological changes (fat liver degeneration, splenomegaly, testicle
      degeneration) induced by CCl4 poisoning in the rat, an effect found also at the
      biological parameters levels studied in plasma and liver. In the plasma, the high
      lipid peroxide concentrations, the increased activity of alkaline phosphatases,
      and the reduced antioxidative activity generated by CCl4 have been statistically
      significant brought to the normal range after Orgasel administration. At the
      liver this treatment significantly decreased the lipid peroxides production, the
      total lipids and cholesterol concentrations, and statistically significant
      increased the enzymes activity (alkaline phosphatases, GPT). The results obtained
      after Orgasel administration proved that this preparation has a global beneficial
      action upon the organism in the poisoned rat, as well as a strong antioxidative
      effect, confirming once again the essential role of Se in maintaining cells'
      integrity.

PMID- 8535347
TI  - Comparative value of effort and adenosine-testing in the evaluation of patients
      with old myocardial infarction.
AB  - Exercise testing (ET) and adenosine testing (AT) coupled with ECG were applied in
      25 patients with old myocardial infarction. ET was positive in 8 (32%) and AT in
      10 (40%) patients, the sensitivity of the latter being slightly superior to the
      former but inferior to the sensitivity reported in the literature for AT
      echocardiography. One should also notice the positivity of AT-ECG in 6 (24%)
      patients, with negative or inconclusive ET, and the double product (DP) at
      ischemic threshold which was twice as low for AT-ECG as for ET-ECG, proving that
      AT induced ischemia by decreasing O2 myocardial input. It is concluded that AT
      ECG is useful in myocardial ischemia detection in association with ET or in
      patients who cannot perform ET for different reasons.

PMID- 8535349
TI  - Lymphocyte subset reference ranges in Romanian adult Caucasians.
AB  - The paper reports the distribution of lymphocyte subpopulations in the Caucasian
      population of Romania. Investigations were carried out in cells bearing the
      following antigens: CD3 (T cells), CD19 (B cells), CD4 (T helper/inducer cells),
      CD8 (T suppressor/cytotoxic and some NK cells), and CD16 CD56 (NK cells).
      Reference values for the lymphocyte subpopulation were obtained from over 100
      healthy Caucasian adult volunteers. Blood from these donors was analyzed using
      FACScan flow cytometer, Leuco-GATE, Simultest and FACS Lysing Solution, and
      SimulSET software. As an internal quality control, it was verified that %T+%B+%NK
      approximates 100% in all samples. The results presented here, obtained on healthy
      donors (51 males and 49 females), showed that there are no statistically
      significant variations of CD4/CD8 ratio related to sex or age, the mean value of
      this ratio (2.0 +/- 0.02) being similar to that reported by the West-European
      countries. Additional similarities were found when the relative percentage, mean
      +/- standard deviation (CD3 = 74.2 +/- 2.8; CD19 = 10.8 +/- 1.6; CD4 = 42.0 +/-
      2.5; CD8 = 28.9 +/- 5.7; CD56 = 15.2 +/- 0.4) and the absolute cell number of the
      major peripheral blood mononuclear subsets established in our study were compared
      with other published results. This study was entirely supported by Becton
      Dickinson--Europe (Division Heidelberg, Germany).

PMID- 8535348
TI  - Serum zinc and copper in patients with cerebral vascular disease.
AB  - Serum Zn and Cu was investigated in 67 patients with cerebral infarction (CI), in
      10 with cerebral hemorrhage (CH), in 14 with transient ischemic attack (TIA) and
      in 58 control subjects (C). Serum Zn concentration is significantly lower in
      patients with CH than in C (p < 0.001), and serum Cu is significantly higher than
      in C in patients with CI (p < 0.005). In patients with CI and in C serum Zn
      concentration decreased with advancing age. The serum Zn concentration decreased
      significantly in patients with CI during hospitalisation (p < 0.001), probably
      due to low intake and insufficient absorption. In patients with CI a significant
      correlation was found between low levels in serum Zn, on the one hand, and serum
      cholinesterase and proteinemia, on the other hand. This suggests a diminution of
      hepatic synthesis of proteins in these patients.

PMID- 8535350
TI  - Dobutamine stress echocardiography.
AB  - Echocardiography is a very good technique for the analysis of total and regional
      left ventricular wall motion. It can be used, in conjunction with a protocol for
      either exercise or pharmacologic cardiovascular stress, to identify the presence
      and distribution of coronary artery disease. The presence of myocardial ischemia
      is proved by the induction by a regional left ventricular wall motion
      abnormality. The use of dobutamine infusion as a stress test associated with
      echocardiography is a practical method, safe and accurate for the diagnosis of
      coronary disease in patients unable to exercise. Dobutamine stress
      echocardiography can also be used for assessment of risk and patient prognosis
      after acute myocardial infarction and as an indicator of myocardial viability.

PMID- 8535351
TI  - Antineutrophil cytoplasmic autoantibodies (ANCA)--markers in diagnosis and
      monitoring systemic vasculitides.
AB  - We present a new class of autoantibodies--ANCA (antineutrophil cytoplasmic
      autoantibodies) which recognize as target antigen different enzyme constituents
      of primary granules of neutrophil granulocytes. These autoantibodies are present
      in a large number of diseases, such as: systemic vasculitides, idiopathic
      crescentic glomerulonephritis, inflammatory bowel diseases and in some other
      conditions, including rheumatoid arthritis, SLE, Felty syndrome, acute and
      chronic infections. ANCA not only facilitate the diagnosis but also have a
      pathophysiological role for some of the idiopathic vasculitides. In our study,
      including 110 patients referred to the laboratory for ANCA testing by indirect
      immunofluorescence technique, only 25 patients were positive with a diffuse
      cytoplasmic (c ANCA) or perinuclear (p-ANCA) pattern on alcohol fixed slides.
      Some relevant cases are presented in order to emphasize that ANCA antibodies are
      a useful marker in the early diagnosis of systemic vasculitides, allowing
      effective therapeutic handling.

PMID- 8535352
TI  - Comparative study of the presence of oxidative stress in sportsmen in competition
      and aged people, as well as the preventive effect of selenium administration.
AB  - The study demonstrates the presence of oxidative stress (OS) in physiological
      conditions in sportsmen in competition and in elderly subjects over 65 years. The
      OS was estimated by measuring some biochemical parameters, such as peroxides,
      total antioxidants, uric acid and free SH groups in plasma and peroxides in
      urine. OS produces a significant increase of peroxides in plasma and urine and a
      decrease of plasma antioxidants and SH groups. The presence of OS suggests an
      increased formation of free radicals in young subjects in sporting competition,
      This increase is subsequently compensated by an increase of antioxidants. In old
      agers, this unbalance remains unchanged. The level of OS is higher in sportsmen
      during competition, but the subsequent compensation depends on the degree of
      training, individual adaptation, diet, etc. The administration of organic
      selenium partially compensates and decreases the intensity of OS. This study
      confirmed the hypothesis that in old agers the formation of free radicals
      increases in the ageing process and recommends the prevention of OS in young
      sportsmen by an adequate protection with antioxidants, such as organic selenium.

PMID- 8535353
TI  - Oxidative stress and antioxidant protection in degenerative psychoorganic
      syndrome in old agers.
AB  - Changes of the redox balance are reflected at the blood level in old agers-
      chronically intoxicated with alcohol--presenting degenerative psycho-organic
      syndromes (DPOS). The parameters investigated were lipid peroxidation reduced
      glutathione and the total SH groups. The changes of the antioxidant enzymatic
      system expressed by the activity of superoxide dysmutase, of glutathione
      peroxidase and of catalase were also followed up. It was observed that compared
      with the control group the lipid peroxides increased by 70.69% and the blood
      concentration of G-SH and of the total SH groups decreased by 46.7% and 24.76%,
      respectively. Likewise enzymes such as GPx and CAT presented increases of 70.4%
      and respectively 68.3% associated with a decrease of 23.9% of SOD activity.

PMID- 8535354
TI  - The role of certain immunologic parameters in silicosis.
AB  - The paper presents some possibilities of estimating the immunologic aggression in
      silicosis in a group of 68 patients divided into three subgroups according to the
      evolutive stage of disease. The results were compared with the data obtained in a
      control group of 35 clinically healthy subjects not subjected to respiratory
      noxae. Parameters such as the immunogram (IgG, IgA IgM, IgD), the C3 complement,
      the circulating immune complexes (CIC) and the C reactive protein (CRP) were
      investigated using classical immunochemical methods. It was observed that the
      immunoglobulin titer presented a polyclonal increase. The mean values of C3
      complement decreased in stages I and II of disease. The CIC level presented high
      mean values unrelated to the stage of the disease. The incidence of CRP was found
      high in stage III. It was demonstrated that there is no significant correlation
      between the humoral immunologic abnormalities and the radiologic changes or the
      depression of the pulmonary functional test. These changes suggest that the
      humoral immunologic abnormalities are not directly responsible for the lung
      changes in silicosis and cannot be used as a predictive indicator of the severity
      of the disease or of its progress. The data obtained showed a hyperreactivity of
      the humoral mediated immunity over the whole course of the disease thus
      supporting the assumption of an immunopathogenic mechanism in this disease.

PMID- 8535355
TI  - Demonstration of the neutrophil granulocyte functional capacity in silicosis,
      using the NBT test.
AB  - The functional capacity of neutrophils was studied using the NBT test in 68
      patients with silicosis in various evolutive stages, comparatively with a group
      of 35 controls. The NBT test showed an initial increase of nonspecific cellular
      reactivity which decreased as the disease evolved. The results in the control
      group showed 9 +/- 5% NBT positive neutrophils. The highest proportion of NBT
      positive neutrophils (17.6 +/- 2.3, p < or = 0.05) was found in stage I of the
      disease and then decreased gradually with the evolution of the disease. The
      proportion of NBT positive neutrophils may be considered as a biochemical marker
      of neutrophil functionality.

PMID- 8535356
TI  - Apolipoprotein (a) concentrations in type 1 (insulin-dependent) diabetes
      mellitus.
AB  - It has been suggested that insulin-dependent diabetes mellitus (IDDM) patients
      have higher values of lipoprotein (a)-Lp (a) that may account for their increased
      atherogenic risk, as related to non-diabetic subjects. We compared the plasma
      values of apolipoprotein (a)-(apo) (a) in type 1 diabetic patients (n = 26)
      hospitalized in our department and in non-diabetic subjects (n = 20) from
      Timisoara, Romania. IDDM patients had higher levels of apo (a) than controls
      [115(102-227) vs 58 (51-106) U/l; medians with 95% confidence intervals]; (p =
      0.0083). Diabetes duration, the levels of hemoglobin A1 (Hb A1) and the values of
      body mass index (BMI) were not significantly related to apo(a) concentrations,
      while no correlations were found between apo (a) and plasma lipid values (total
      cholesterol (TC), low density lipoprotein cholesterol (LDLc), high density
      lipoprotein cholesterol (HDLc), triglyceride. A significant association was
      noticed between apo (a) and apo B both in IDDM patients (r = 0.43; 0.02 < p <
      0.05), and in controls (r = 0.83; p < 0.001). We conclude that apo (a) levels are
      higher in IDDM patients than in non-diabetic subjects, but they are not related
      to the degree of glycemic control. Apo (a) and apo B are significantly
      correlated, both of them being well-known atherogenic risk factors.

PMID- 8535357
TI  - Apolipoprotein(a) concentrations in type 2 (non-insulin dependent) diabetic
      patients from Romania.
AB  - Several studies suggested that lipoprotein (a)-Lp(a) is an independent
      atherogenic risk factor. Since non-insulin-dependent diabetes mellitus (NIDDM) is
      characterized by an increased risk of coronary heart disease (CHD) as related to
      the general population, the main purpose of our study was to compare the plasma
      levels of apolipoprotein (a)-(apo) (a) in 30 NIDDM patients hospitalized in our
      department, and in 20 non-diabetic controls from Timisoara. Apo (a) values were
      similar in the two groups (medians, 95% confidence intervals 57 (50-107) in NIDDM
      versus 58 (51-106) U/l in controls; p = 0.9097). We found weak correlations
      between apo (a) and hemoglobin A1 (HbA1) (r = 0.42). A significant association
      was noticed between apo (a) and apo B, both in NIDDM (r = 0.71) and in control
      subjects (r = 0.81) p < < 0.001. The diabetic patients were screened for
      microalbuminaria with the MICRAL-test and we compared apo (a) levels in those
      having albumin excretion values above and under the cut-off point (20 mg/l). Apo
      (a) concentrations were similar in both samples. We found no association between
      apo (a) and plasma lipid values. NIDDM patients on fair glycemic control have
      similar apo (a) concentrations to non-diabetic subjects and they do not seem to
      be influenced by diabetes duration, HbA1, microalbuminuria and plasma lipid
      values Apo (a) and apo B are significantly correlated, both in diabetic and non
      diabetic subjects.

PMID- 8535358
TI  - Correlations between spondylarthropathic inflammatory troubles and gonadal
      (androgenic) troubles in men. Study on 30 cases with a new methodological
      analysis.
AB  - Ankylosing spondylitis (AS) and spondylarthropathies (SAP), proposed immune
      diseases, present sexual preponderance: men are mostly affected. It is known that
      androgens are decreased in systemic immune disorders. We have investigated two
      aspects: gonadal--with 13 parameters, and entheso-osteoarthritic--with 10
      parameters, by an original methodological semiquantitative analysis. All the
      parameters were divided into five degrees; each degree was pointed from 0 to 5,
      and the total and final scores were obtained. In this way differences and
      correlations could be performed between all 23 parameters. We have studied 30 SAP
      patients in inflammatory attack, 4 SAP patients out of the inflammatory attack
      and 16 control subjects; all were men and in fertile age. Between the gonadal
      status of SAP patients vs the control group there is a significant difference
      concerning: the degree of testosterone (1.81 vs 0.22, p < 0.005) and testes
      trophicity (1.5 vs 0.35, p < 0.01); marked differences have been recorded for
      integrative scores: total (12.18 vs 6.21, p < 0.02), final (1.07 vs 0.57, p <
      0.01) and general degree score (1.7 vs 1.18, p < 0.01). Testosteronemia has been
      different, too: 7.38 vs 23.25 nmol/l, p < 0.01. Between SAP patients in and out
      of the inflammatory attack there are no significant differences. A significant
      positive correlation between gonadal axis status degree and entheso
      osteoarthritic status degree has been obtained by Spearman rank test: r = 0.41, p
      < 0.05. Our new methodological analysis allows to change qualitative criteria in
      mathematical used quantitative data, for performing correlations between so
      different fields: rheumatological and endocrinological. SAP patients (in
      inflammatory attack, and out of the inflammatory attack) have a certain degree of
      hypogonadism, which does not represent a specific disease but suggests a specific
      spondylarthropathic background.

PMID- 8535359
TI  - Department of Defense leading breast cancer research into the future.

PMID- 8535360
TI  - National Breast Cancer Action Plan: doing things differently.

PMID- 8535361
TI  - Are there new perinatal treatment recommendations for decreasing vertical
      transmission of human immunodeficiency virus (HIV)?

PMID- 8535362
TI  - Shortened maternity, newborn stay issue gaining momentum.

PMID- 8535363
TI  - CRFA focuses on breast cancer prevention, early detection.

PMID- 8535364
TI  - AWHONN and breast cancer--what can we do?

PMID- 8535365
TI  - Prostate cancer in Czech Republic 1959-1992. Descriptive survey.
AB  - Carcinoma of the prostate is the second most common cancer and fourth most common
      cause of death from cancer, among men in Czech Republic. Of all tumours, the
      prevalence of prostate cancer increases the most rapidly with age. A shift in age
      distribution favouring the older population as a consequence of health promotion
      and disease prevention programmes, will lead to a permanent increase in the
      number of patients diagnosed with prostate cancer in Czech males. Its incidence
      is raising steadily and about 2/3 of all new cases are diagnosed at the time of
      extra-prostatic or distant disease with poor prognosis for cure. Current evidence
      especially from the USA strongly suggests that combing the improving prostate
      specific antigen test (Hybritech Tandem assay) with the digital rectal
      examination increases the early detection rate for prostate cancer.
      Implementation of this scheme to routine diagnostics can offer the best chance of
      increased survival, decreased morbidity and possible cure of the Czech males.

PMID- 8535366
TI  - History of poliomyelitis in the Czech Republic--Part III.
AB  - The "repression phase" of paralytic poliomyelitis in the Czech Republic (and in
      the Slovak Republic as well) between 1957 and 1960 was characterized by
      controlled, short term, mass vaccination campaigns. In spring 1957, at the very
      beginning of a polio epidemic, about 87% of all children aged 1 to 7 years and
      about 40% of those aged 8 to 15 years were intradermally vaccinated with IPV. The
      protective effect in population given two IPV doses was 66% (in Slovakia 74%).
      The starting epidemic of 1957 was stopped. Morbidity and mortality from
      poliomyelitis markedly decreased in 1958. Nevertheless, about 39%, 13% and 41% of
      children aged under 8 years (given three IPV doses) had not specific virus
      neutralizing antibodies against polioviruses types 1, 2 and 3 respectively. A
      field trial with OPV started in winter 1958-59. Over 110,000 children aged 2 to 6
      years were vaccinated with Sabin OPV, which proved to be safe, highly immunogenic
      and protective. In spring 1960 about 93% of children were vaccinated in the
      former Czechoslovakia with OPV in a mass, countrywide campaign. No case of
      paralytic poliomyelitis was reported during the second half of 1960. The same was
      true for all year 1961, the first year of the historical period of poliomyelitis
      elimination in our country.

PMID- 8535367
TI  - Fungicide methfuroxan administered chronically to rats did not affect serum
      thyroid hormone levels.

PMID- 8535368
TI  - An outbreak of gentamicin-resistant Klebsiella pneumoniae in a neonatal ward.
AB  - Gentamicin-resistant Klebsiella pneumoniae (GRKP) was isolated from nineteen
      patients in the neonatal ward of Sultan Qaboos University Hospital (SQUH) in
      Oman. Thirteen cases were infected and six were colonized. Two infected patients
      died due to septicaemia, eight cases occurred within SQUH and eleven cases were
      imported from other hospitals. Sixteen isolates were of the same serotype (K25),
      three were non typeable. Referred patients from peripheral hospitals were the
      source of the organism and hand carriage the probable vehicle of transmission.
      The first strain of gentamicin-sensitive Kleb. pneumoniae was isolated five
      months after combating the outbreak.

PMID- 8535369
TI  - Chronic influence of pyrethroid supermethrin on some reproductive features in
      Japanese quail (140 days long avian reproduction test).
AB  - We observed the influence of chronic effect of pyrethroid supermethrin on some
      reproduction features in Japanese quails. They received 3 different doses (P1
      10.7 mg.kg-1.day-1; P2 21.4 mg.kg-1.day-1 and P3 35.7 mg.kg-1.day-1) of the
      tested substance during 20 weeks. The total health status, reproduction of
      Japanese quails, the damage rate (degree) of the organs and tissues as well as
      the determination of residue in the eggs and muscles of the experimental birds
      showed that pyrethroid insecticide supermethrin can be considered a safe
      pesticide.

PMID- 8535370
TI  - Prevalence of Lyme borrelia in ticks in Bratislava, Slovak Republic.
AB  - A total of 2857 unfed Ixodes ricinus adult ticks were collected in 2-3 week
      intervals in 1991 in Bratislava to survey their prevalence with spirochaetes.
      Five hundred twenty eight, i.e. 17.8% harboured borreliae as detected by dark
      field microscopy. The infection rates of examined ticks varied from 15.3 to 21.8%
      in females and from 14.5 to 16.9% in males. The infestation of ticks was related
      to the season of their collection, the highest being in summer months. At this
      time the highest number of spirochaetes per tick was seen, too. Tick infestation
      with spirochaetes in March and April 1991/92 and 1992/93 at 13 and 9.3%
      respectively, indicated borreliae do hibernate in these arthropods. The strain
      isolated from two females collected in October 1992 was determined by PCR typing
      as Borrelia garinii. Out of 371 patients suspected in Derer's Hospital,
      Bratislava, from Lyme disease, 81 (21.8%) had antibodies to B. burgdorferi. This
      demonstrates the presence of Lyme disease in Bratislava with Ixodes ricinus ticks
      being probably a vector of that spirochaetosis.

PMID- 8535371
TI  - Adverse reactions to BCG.
AB  - In the post-war period the following BCG vaccines were successively in use for
      preventive vaccination in the Czech territory: (a) Copenhagen BCG, 1947-1950, (b)
      Prague BCG 725, 1951-1980, (c) Moscow BCG, 1981-1993, and (d) Behring BCG, from
      1994 onwards. These BCG substrains can be now identified by modern methods of
      molecular genetics. Introducing the Moscow BCG brought about an elevated
      incidence of iatrogenic local and regional lymph node adverse reactions compared
      with the previous Prague BCG product and, as a new phenomenon, bone and joint
      involvements in children vaccinated at birth. The aim of this study was to
      analyze the incidence of postvaccination adverse reactions reported in the period
      from 1981 to 1993 as related to the Moscow BCG vaccine and, to demonstrate the
      effect of lower vaccination dosage on their frequency. The concentration of the
      Moscow BCG varied from 11 to 22.6 x 10(6) (average 16.2) CFU per 1 mg. In the
      period when full dose of BCG (0.05 mg per 0.1 ml) was applied to newborns 437
      local and 195 regional lymph node complications were recorded, i.e. 0.08% of
      vaccinated were affected, demanding antituberculosis chemotherapy in 6.5% and
      surgical interventions in 24%. When the lowered vaccination dose (0.025 mg per
      0.1 ml) was inoculated to newborns the local adverse reactions rose paradoxically
      affecting 0.1% of vaccinated but the regional lymph node reactions fell
      considerably to reach 0.01%; the demand for chemotherapy and surgery also fell
      down to 3.1 and 4.8% respectively. Bone and joint adverse involvements were
      recorded in 28 cases, i.e. in 3.7 per 10(5) of those vaccinated with the full
      dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535372
TI  - Crude oil spill in sea water: an assessment of the risk for bathers correlated to
      benzo(a)pyrene exposure.
AB  - In the spring of 1991, there was a shipwreck of the oil tanker "Haven" off the
      Ligurian coast of Italy. This resulted in the spillage of a very large amount of
      crude oil, some of which was burned off by fire. The accident caused several
      serious problems (sea and air pollution, damage to the marine fauna, risk of
      human exposure, etc.). In this context, an assessment was carried out at the
      Istituto Superior di Sanita with the aim of determining any possible risks to
      humans which might derive from bathing activities during the following summer
      season. The whole evaluation carried out after the accident demonstrated that the
      impacts induced were not serious enough to require bathing restrictions in the
      coastal areas involved. Assuming a benzo(a)pyrene (BaP) concentration in sea
      water of 1 microgram/m3 cancer risk is in the order of 10(-8) and in the case of
      10-kg child, a 10(-6) risk level correspond to about 0.18 microgram/l of BaP in
      sea water.

PMID- 8535373
TI  - The spring-fall variations in the prevalence of environmental mycobacteria in
      drinking water supply system.
AB  - The fluctuation in the prevalence of environmental mycobacteria in relation to
      nutritional conditions in nature was repeatedly described in literature. The
      seasonal difference in potable water supply system has not yet been documented.
      Potable water samples from water supply systems of 16 localities were analyzed.
      The samples of running water, and tap swabs or tap scrapings were collected twice
      a year, in the spring and in the autumn. McNemar's test was used to analyze the
      difference of the occurrence of environmental mycobacteria between the vernal and
      the autumnal samples. A significant change in the presence of environmental
      mycobacteria in the potable water supply system was observed: the vernal samples
      yielded more positive results. This finding supports other observations of
      superficial water. We infer that this effect in potable water supply system may
      be caused by the change in temperature. Contamination rates were similar with no
      statistically significant difference between running water samples and that of
      swabs or scraping. No time trend in the period 1984-1989 in the prevalence of
      mycobacteria was detected. Direct microscopy showed massive colonisation with
      environmental mycobacteria of potable water supply system. Public health
      consequences of these findings should be further evaluated, as colonisation of
      water pipes can be associated with outbreaks of mycobacterial disease in
      immunocompromised patients. There has been also an increase in the incidence of
      mycobacterioses in North Moravian Region in recent years.

PMID- 8535374
TI  - Interaction of virulent and non-virulent Yersinia enterocolitica strains and an
      epithelial and a phagocytic cell lines.
AB  - Morphological alterations of HEp-2 and P338D1 cells were detected as result of
      Yersinia virulent strains action only. A non-virulent strain caused none of these
      alterations even 24 h post infection (p.i.). The internalization of the bacteria
      was demonstrated by double fluorescence staining. Adherence and beginning of cell
      invasion of virulent strains was detected 30 min p.i. already. Two hours p.i.
      these bacteria were in great numbers inside the cells of both lines. The non
      virulent Yersinia strain was found only in the P338D1 macrophages at 2 and 24 h
      p.i. but in smaller numbers than virulent strains. Electron microscopy confirmed
      that internalization of virulent strains Y526 and Y527 was done by the
      phagocytosis of both cell lines. Even intracellular replication of these virulent
      strains was observed in both cell lines at 2 and 24 h p.i. Both bacterial strains
      were disintegrated as well as they multiplied inside the cells. In strain Y526
      disintegration of bacteria prevailed, whereas their replication predominated in
      the strain Y527. At 24 h p.i. cells infected with strain Y527 were sac-like, with
      rudiments of the cytoplasm and organelles, packed with bacteria that were
      released after cell membrane rupture. Cells infected with strain Y526 were
      metabolically active and even at 24 h p.i. predominately contained disintegrated
      bacteria, but even in this case replication and release of bacteria was observed.

PMID- 8535375
TI  - People on the garbage dumps of Cairo: a toxicological in vivo model?
AB  - In the outskirts of Cairo, some 40,000 people live on garbage dumps. These people
      form a closed population whose socio-economic problems are identical. The
      pollutants are evenly distributed. Up to 30% of the garbage on the polluted area,
      which cannot be recycled, is burned, resulting in a high concentration of
      pollutants in the environment. The concentrations of heavy metals,
      dioxins/furans, PCB, PAH in dust deposit and soil were measured as well as the
      air pollutants SO2, HCl and CO. It was shown that while the systemic immune
      system is only affected to a very small degree, secretory immunoglobulin A is
      strongly affected by the emissions. It could be demonstrated also an increased
      readiness for allergic respiratory disease, through the proof of hyperreactive
      mucous membranes. In the polluted area, 58% of the examined children were
      affected, whereas in the control area only 22% displayed a hyperreactive mucous
      membrane. Also the concentration of NANA (N-acetyl-N-neuraminic acid) in the
      serum, as a unspecific marker of cell irritation, was high in the serum of
      children from the polluted area. Most of the pollutants detected can also be
      observed in the industrialized regions, especially in combination with
      incinerating plants. In this way, this study suggests the synergistic effects of
      pollutants.

PMID- 8535376
TI  - Relation between residential radon concentrations and housing characteristics.
      The Cracow Study.
AB  - The survey on indoor radon exposure was undertaken to explain whether the excess
      in lung cancer deaths in Cracow city center may be attributed to this particular
      exposure. A total of 310 detectors was placed in households randomly chosen from
      three homogenous strata of residential buildings. The first stratum included
      house in the old city center constructed predominantly out of the stone bricks.
      The second stratum covered area of the city with big apartment condominiums built
      out of concrete blocks. The third stratum consisted of single family houses
      located in a suburban area. From each of these residency strata a random sample
      of equal number of households has been chosen and the radon detectors were placed
      in households located at different levels of buildings. The three-month radon
      sampling data were used to determine the distribution of various levels of radon
      in the households. In the measurement of radon exposure the Landauer alpha-track
      samplers were used. The data collected show that the best single predictor of
      indoor radon concentrations was type of building. Other variables found to be
      associated significantly with indoor concentrations were household level in the
      building and house age. In general, residences with a concrete slabs and
      dwellings with rarely-opened windows were found to have slightly higher radon
      concentrations.

PMID- 8535377
TI  - Salmonella phage types distribution in the Czech Republic in 1991-1994.
AB  - The Salmonella enteritidis and Salmonella typhimurium phage types in the Czech
      Republic during the monitored period 1991-1994 are described. The total number of
      2318 strains were examined. From 652 Salmonella typhimurium strains 24 various
      phage types were identified. PT 104 was predominating in both human and non-human
      strains. 1666 of Salmonella enteritidis strains were identified and were
      representative of 14 different phage types. PT 8 was the most common type in
      humans (91.7%) and in animals (79.1%).

PMID- 8535379
TI  - Drug Utilization Research and Pharmacoepidemiology meeting. Utrecht, the
      Netherlands, 19 May 1995. Abstracts.

PMID- 8535378
TI  - Environmental impact, healthful food and education in toxicology--trends in
      Croatia.
AB  - Following the informative regional development and environmental impacts in the
      Republic of Croatia, authors present the problems emphasized in environmental
      protection and health protection, and present the status of the contamination of
      food and drinking water in 1993. The level of education in the function of
      environmental protection in Croatia and its importance are discussed.

PMID- 8535380
TI  - Advanced Activities in Pharmaceutical Care, 24th European Symposium on Clinical
      Pharmacy. Prague, Czech Republic, 10-13 October 1995. Abstracts.

PMID- 8535381
TI  - 5th Symposium of the European Society for the Study of Purine and Pyrimidine
      Metabolism in Man. Termoli, Italy, 4-8 October 1995. Abstracts.

PMID- 8535382
TI  - Object relations units and the ego.
AB  - The author selectively reviews the literature on object relations units and
      suggests that a fourth element, ego functioning, should be added to self, object,
      and affect-sensation for a more clinically comprehensive theory. He suggests that
      ego functioning may always shift with self, object, and affect-perception in an
      organically integrated fashion. Such a conceptualization can apply to both
      healthier and less well-integrated individuals. This expanded concept may or may
      not be sufficiently comprehensive to replace the traditional structural theory of
      id, ego, and superego.

PMID- 8535383
TI  - Resistance and modes of communication.
AB  - The recognition that there are three modes of thinking and communicating--iconic,
      enactive, and symbolic--clarifies and simplifies many issues in psychoanalytic
      theory and technique. Although this concept is applicable to all communication,
      it is particularly important in understanding and interpreting various types of
      resistance. The author uses a number of vignettes to illustrate the forms and
      functions of various types of nonverbal communication within the psychoanalytic
      process.

PMID- 8535384
TI  - Autistic defenses and the impairment of cognitive development.
AB  - The authors suggest that unbearable early life experiences that force the infant
      to use autistic defenses often constitute a significant factor leading to
      cognitive impairment. These autistic defenses are self-generated (sensory)
      soothing devices that shut out consciousness of the world and foreclose the need
      to relate to anyone or anything that is not under the complete control of the
      subject. Two clinical examples are given from opposite ends of a continuum of
      patients with varying degrees of cognitive impairment.

PMID- 8535385
TI  - Patterns of symptomatic change in depressed patients in a private inpatient mood
      disorders program.
AB  - This naturalistic study of 352 depressed patients admitted to a mood disorders
      program in a private psychiatric hospital demonstrated that, for the majority of
      patients, combining cognitive group therapy with ongoing supportive individual,
      psychoeducational, milieu, and pharmacological interventions resulted in rapid
      overall improvement and discharge within a few weeks. Improvement was manifested
      across cognitive and vegetative factor scores of the Beck Depression Inventory.
      However, patterns of symptom remission differed for subgroups defined by
      different lengths of stay. For example, patients hospitalized for 4 weeks showed
      good initial response, followed by a plateau in improvement, and, finally,
      continued response. These patients eventually reached the same level of
      functioning at discharge as did more rapidly responding patients with briefer
      stays. In contrast, a subset of patients (10% of the sample) hospitalized 5 weeks
      or more showed less overall improvement (especially in vegetative symptoms),
      plateauing at a moderately symptomatic level. These data suggest that in a
      minority of depressed individuals, continuing physiological disturbances may
      underlie dysthymia or residual depression. However, in contrast to the high rates
      (20-30%) of chronicity reported from tertiary care settings, these data indicate
      the relatively good initial treatment response of depressed patients admitted to
      a private psychiatric hospital.

PMID- 8535386
TI  - Obsessive-compulsive symptoms and the family.
AB  - A questionnaire study of 98 family members of individuals with obsessive
      compulsive symptoms revealed that 60% of the family members were involved to some
      extent in rituals with the affected family member. Nearly all family members
      reported at least some degree of interference in their lives. Information was
      also gathered about the sort of rituals in which members were involved, how they
      responded to the demands of the affected relative to engage in the rituals, their
      beliefs and knowledge about compliance, and the degree to which the rituals
      interfered in their lives. The study highlights the possible need for support,
      advice, and education for family members of persons with obsessive-compulsive
      symptoms.

PMID- 8535387
TI  - The comforting substrate and the right brain.
AB  - The author tested the hypothesis that the comforting substrate is located in the
      right parietal area of the brain. Sixty subjects (39 women, 21 men) were given
      two forced-choice tasks treated as comparison experiments. Given the choice
      between two identical bright red balls (one on the left and one on the right),
      only 20% of the right-handed subjects chose the left ball (p < .01). Given the
      choice between identical stuffed, white bears, which were described as grieving
      and urgently in need of comfort, 54.5% of the subjects chose the left bear (p <
      .05, with ball selection as control and analyzed by the binomial). Considering
      only discordant pairs (left bear-right ball combination or vice versa), 20 of 23
      subjects chose the left bear (p < .0002). Results suggest the possibility that
      right-brain lateralization of the comforting substrate is more pronounced among
      females, especially mothers.

PMID- 8535388
TI  - Transactions of the Topeka Psychoanalytic Society. Self-destructive behavior in
      young people.

PMID- 8535389
TI  - Estimation of bloodstain age by rapid determinations of oxyhemoglobin by use of
      oxygen electrode and total hemoglobin.
AB  - Bloodstain age could be estimated from the ratio of oxyhemoglobin/total
      hemoglobin (fractional oxyhemoglobin) in the bloodstain by this present method,
      if the temperature at which the bloodstain had been kept was known. The
      oxyhemoglobin was determined with an oxygen electrode immersed in water in which
      the oxygen had been depleted, and the total hemoglobin was determined by
      conventional colorimetry (cyanomethemoglobin method). Ages of prepared bloodstain
      samples (within 24 h after bleeding) were estimated by this present method, which
      requires only 20 microliters of bloodstain and only 5 min for the whole analysis.

PMID- 8535390
TI  - A sensitive ELISA for the characterization of two forms of circulating
      intercellular adhesion molecule-1 in human plasma.
AB  - Nine murine monoclonal antibodies (MAbs) raised against recombinant soluble
      intercellular adhesion molecule-1 (sICAM-1) were evaluated by means of ELISAs,
      and their neutralizing activity was investigated in two bioassays employing Raji
      cells activated with phorbol myristate acetate. Three of the MAbs inhibited
      autoaggregation of the activated cells and adhesion to sICAM-1 fixed on a plastic
      plate. Non-neutralizing antibody SM1-255 is directed to an epitope that was not
      recognized by the other eight MAbs. This property enabled us to develop two
      ELISAs employing SM1-255 as a liquid-phase antibody for the quantitation of sICAM
      1 circulating (cICAM-1) in human plasma. One assay, employing non-neutralizing
      antibody WIS2-11 as a solid-phase, has a sensitivity of two pg/well with
      coefficients of variation of 3.6-5.8% (within assay) and 5.5-9.5% (between
      assay). The other assay, employing neutralizing antibody WIS5-85 as a solid
      phase, has a sensitivity of four pg/well with coefficients of variation of 2.7
      7.2% (within assay) and 9.2-11.2% (between assay). There was a discrepancy
      between cICAM-1 levels of human plasma determined by these two assays. All
      samples showed 2- to 5-times higher levels in the assay using WIS2-11 than in
      that using WIS5-85. The result from the gel electrophoresis employing Western
      blotting suggests that ICAM-1 circulates in at least two molecular forms with
      molecular masses of about 85 and 130 kDa and with different reactivities to WIS2
      11 and WIS5-85.

PMID- 8535391
TI  - Stereospecific dehydrogenation of (25R)- and (25S)-3 alpha,7 alpha,12 alpha
      trihydroxy-5 beta-cholestanoic acids by acyl-CoA oxidase in rat liver light
      mitochondrial fraction.
AB  - From a stereochemical point of view, the dehydrogenation mechanism of the
      biotransformation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid
      (THCA) into (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic
      acid (delta 24-THCA) has been studied with capillary gas chromatography
      (GC)/negative ion chemical ionization (NICI)-mass spectrometry. After incubation
      of (24R,25R)- or (24S,25S)-[24,25-2H2]THCA, synthesized from (24E)-delta 24-THCA
      by a deuterated diimide reduction, with a rat liver light mitochondrial fraction,
      5 beta-cholestanoic acids were extracted and derivatized into a pentafluorobenzyl
      (PFB) ester-dimethylethylsilyl (DMES) ether. Subsequent resolution into THCA and
      delta 24-THCA was attained by GC on a cross-linked 5% phenylmethyl silicone fused
      silica capillary column monitored with a corresponding characteristic carboxylate
      anion [M-PFB]- in the NICI mode. The stereospecific elimination of a pro-R
      hydrogen at C-24 in both (25R)- and (25S)-THCA indicated syn-elimination for the
      former, whereas anti-elimination for the latter was observed.

PMID- 8535392
TI  - Reconstitution of an iron-sulfur cluster with bound sulfur: a possible source of
      acid-labile sulfur in biological systems.
AB  - The reconstitution of the iron-sulfur cluster of spinach ferredoxin was examined
      in vitro using low and high molecular bound sulfur components as sulfur donors.
      Bound sulfur was rapidly converted to acid-labile sulfur to form an iron-sulfur
      center in the presence of dihydrolipoate and iron. Reconstitution yields of above
      95% were obtained with cystine trisulfide (CT, 0.25 mM) and sulfur-bound albumin
      (SBA, 1.0 mM) at 37 degrees C, pH 7.3, following 60 min incubation. Spectroscopic
      features and biological activity of the reconstituted ferredoxin were identical
      to those of the native holo-protein. The acid-labile sulfur content found in the
      isolated reconstituted ferredoxin was 2 atoms/mol protein, similar to the
      theoretical value. A possible role for bound sulfur in mammalian cells is
      indicated and discussed.

PMID- 8535393
TI  - Purification and cDNA cloning of an antifungal protein from the hemolymph of
      Holotrichia diomphalia larvae.
AB  - An antifungal protein (AFP), holotricin 3, was purified from the hemolymph of the
      coleopteran insect Holotrichia diomphalia larvae. Analysis of its cDNA showed
      that holotricin 3 is a novel Gly- and His-rich protein consisting of 84 amino
      acid residues. This protein was similar to AFP, an antifungal protein of
      Sarcophaga peregrina that was reported previously, in terms of molecular size and
      high content of Gly and His residues. However, no appreciable sequence similarity
      was detected between the two proteins.

PMID- 8535394
TI  - Helicobacter pylori urease inhibition by rabeprazole, a proton pump inhibitor.
AB  - We investigated the inhibitory effects of four gastric proton pump inhibitors
      (PPIs): rabeprazole, a novel benzimidazole PPI, omeprazole, lansoprazole and AG
      2000, on the urease activity of Helicobacter pylori (H. pylori). Their 50%
      inhibitory concentrations (I50s) were found to be 0.29, 5.4, 9.3 and 0.3 microM
      respectively. Rabeprazole and omeprazole were also potent inhibitors of Jack bean
      and Proteus mirabilis cellular ureases. The thioether derivative of rabeprazole,
      one of its metabolites, had no inhibitory effect on H. pylori urease, despite
      being reported as a more potent inhibitor of H. pylori growth than rabeprazole.
      The inhibitory effect of rabeprazole was prevented completely and reversed
      considerably by the addition of sulfhydryl compounds, such as beta
      mercaptoethanol, glutathione and dithiothreitol. Moreover, the addition of beta
      mercaptoethanol recovered the urease activity inhibited by rabeprazole. From
      these results, we expected that rabeprazole inhibited H. pylori urease activity
      by forming disulfide bonds between it and the active site of the enzyme.

PMID- 8535395
TI  - Structure and activity of HYI killer toxin from Hansenula saturnus.
AB  - The primary structure of HYI killer toxin produced by Hansenula saturnus was
      determined in its reduced and pyridylethylated form, as well as the peptides
      resulting from protease digestion. It was found that the HYI killer toxin
      consisted of 87 amino acid residues and the molecular weight was calculated to be
      9543 Da. It showed 87% homology with HM-1 killer toxin produced by H. mrakii,
      while there were multiple mutations including one amino acid deletion which,
      nevertheless, did not alter the strong cytocidal effect on sensitive yeasts.

PMID- 8535396
TI  - Cytochrome P450 isozymes involved in aromatic hydroxylation and side-chain N
      desisopropylation of alprenolol in rat liver microsomes.
AB  - Alprenolol 4-hydroxylation and N-desisopropylation in liver microsomes from male
      Wistar rats were kinetically analyzed to be biphasic. In the 4-hydroxylation at a
      low substrate concentration (5 microM), significant strain [Wistar > Dark Agouti
      (DA)] and sex (male > female) differences were observed, and the differences
      decreased at a high substrate concentration (1 mM). In the N-desisopropylation,
      only a strain difference (Wistar > DA) was observed at the low substrate
      concentration. Cytochrome P450BTL (P450BTL, corresponding to CYP2D2) in a
      reconstituted system with 5 microM alprenolol had high 4-hydroxylase activity,
      which was about 10 times that of P450ml corresponding to CYP2C11, and N
      desisopropylase activity at a similar extent to P450ml. The two microsomal
      activities at 5 microM alprenolol were efficiently decreased by antibodies
      against P450BTL and by sparteine, a typical substrate of the CYP2D subfamily.
      Polyclonal antibodies against P450ml and P450PB-1 (corresponding to CYP3A2)
      partially suppressed only N-desalkylation at 5 microM, whereas they reduced the
      two activities at 1 mM. P450ml showed a high N-desisopropylase activity at a
      substrate concentration of 1 mM, where the sex difference was not observed.
      Furthermore, P450PB-2 corresponding to CYP2C6, which is one of the major P450
      isozymes in female rats, also had 4-hydroxylase and N-desalkylase activities.
      These results suggest that a CYP2D isozyme(s) is the primary enzyme in alprenolol
      4-hydroxylation and N-desisopropylation in a lower substrate concentration range,
      and that the involvement of some male-specific P450 isozyme(s) other than CYP2C11
      or CYP3A2 may cause the sex difference in the 4-hydroxylation. In a higher
      substrate concentration range, CYP2C11 is thought to play a major role
      particularly in N-desisopropylation in male rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8535397
TI  - Bopindolol is a slowly dissociating beta 1-adrenoceptor antagonist when compared
      to other beta-blockers.
AB  - This study used radioligand binding assay methods and pharmacological experiments
      to examine whether bopindolol, possessing a long-lasting action in addition to
      potent beta-adrenoceptor antagonistic effects, is a slowly dissociating
      antagonist. In addition, the slow dissociation of two of its metabolites, 18-502
      (4-(3-tert-butylamino-2-hydroxypropoxy)-2-methyl indole) and 20-785 (4-(3-tert
      butylaminopropoxy)-2-carboxyl indole), which have potent beta-blocking
      activities, was also assessed. The blockade of 3H-CGP12177 binding sites in rat
      heart and brain induced by pindolol was readily reversed by washing, whereas this
      inhibition by bopindolol and 18-502 was not easily reversed by washing. In
      addition, specific bindings of the hearts of the treatment animals with 20-785,
      atenolol, (+/-)propranolol, nadolol and celiprolol and of washout were 86.7,
      78.8, 77.5, 82.3 and 79.9% of the control, respectively. These blockades by the
      treatment of each drug and washout in the brain were, however, lower than those
      in the hearts. On the other hand, when the left and right atria were pretreated
      with propranolol, bopindolol and 18-502, the inotropic and chronotropic actions
      of isoprenaline were inhibited by these drugs even though they were not present
      in the extracellular medium. Pretreatment with 20-785, atenolol and nadolol was
      readily reversed for both inotropic action and chronotropic rate, and inhibition
      by celiprolol and pindolol remained at 25% of the control at 240 min after
      treatment with these drugs. A good correlation between inhibitory binding
      percentage in the hearts and inhibitory inotropic or chronotropic actions were
      observed, although it was not observed in the brain.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8535398
TI  - Studies on the activation mechanisms of guanylyl cyclase by serotonin, probably
      through a novel subtype of serotonin receptor (5-HTGC).
AB  - Characterization of the serotonin-induced increase in guanosine 3',5'-cyclic
      monophosphate (cyclic GMP) was investigated and compared with that induced by
      atrial natriuretic peptide (ANP) in NG108-15 cells. The cyclic GMP formed by
      serotonin or ANP was transported in a similar manner to the extracellular medium,
      although the cyclic GMP formed by bradykinin was not. Serotonin and ANP raised
      cyclic GMP additively. Serotonin-induced cyclic GMP formation was completely
      inhibited by pretreatment with 100 nM 12-o-tetradecanoylphorbol 13-acetate (TPA),
      although that induced by ANP was only partially inhibited and the effects were
      blocked by pretreatment with staurosporin. In membrane preparations, ANP
      stimulated cyclic GMP formation in the presence of ATP, but serotonin did not.
      Serotonin-stimulated cyclic GMP formation was found to occur in neuroblastoma
      N18TG-2, but not in glioma C6Bu-1. These results suggest that a novel subtype of
      serotonin receptors (5-HTGC) which stimulates membrane-bound guanylyl cyclase,
      different from that stimulated by natriuretic peptide, may exist especially in
      neurons.

PMID- 8535399
TI  - Inhibitory effect of sodium 5,6-benzylidene ascorbate (SBA) on the elevation of
      melanin biosynthesis induced by ultraviolet-A (UV-A) light in cultured B-16
      melanoma cells.
AB  - Sodium 5,6-benzylidene ascorbate (SBA) is a conjugate of ascorbic acid (Asc) with
      benzyaldehyde. It has been found that the antioxidant activity of SBA is more
      stable and has a longer lifetime in living cells and organs than Asc. In this
      study, we investigated the effect of SBA on the induction of melanin in cultured
      melanoma (B-16) cells irradiated by UV-A. Melanin content of B-16 cells was
      significantly increased by UV-A irradiation. The induction was abolished by
      mannitol and particularly by superoxide dismutase, suggesting the involvement of
      O2- in the biosynthesis of melanin in cultured melanoma cells. This was theorized
      by the fact that the induction was also observed in B-16 cells treated with
      superoxide anion radicals chemically generated in the hypoxanthine/xanthine
      oxidase-reaction system, instead of UV-A irradiation. The induction of melanin
      caused by UV-A irradiation was suppressed by SBA in a dose-dependent manner. To
      elucidate the mechanism of this suppressive effect, the scavenging activity
      against O2-, and the inhibitory effect of SBA on tyrosinase activity were
      examined. ESR spectrometric analysis showed that SBA strongly scavenged O2-, and
      the presence of SBA in the medium remarkably inhibited the tyrosinase activity in
      cultured B-16 melanoma cells. It can be concluded that SBA effectively inhibits
      the melanin biosynthesis in B-16 melanoma cells induced by reactive oxygen
      species (ROS) generated by UV-A irradiation via tyrosinase.

PMID- 8535400
TI  - Inhibitory effect of pyridobenzazoles on virus replication in vitro.
AB  - Twelve species of pyridobenzazoles and pyrimidobenzimidazole were examined as
      inhibitors of the replication of respiratory syncytial virus (RSV) in HeLa cells.
      From the pyridobenzazoles studied, 2-benzamido-4-cyano-1-oxo-1H,5H-pyrido[1,2
      alpha]benzimidazol emerged as a potent inhibitor of the RSV. Based on its
      inhibitory effect on the cytopathogenicity of the RSV in HeLa cells, the 50%
      effective dose was found to be 0.95 micrograms/ml. The cytotoxicity of this
      compound for HeLa cells was examined by monitoring the incorporation of
      radiolabeled uridine into cellular RNA. The selectivity index was ca. 30, the
      same as Virazole.

PMID- 8535401
TI  - Increase in total blood leukocyte count following intranasal administration of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits with
      cyclophosphamide-induced leukopenia.
AB  - We investigated the effects of intranasal (i.n.) administration of recombinant
      human granulocyte colony-stimulating factors (rhG-CSF) on the total count of
      leukocytes in peripheral blood (total blood leukocyte count) of rabbits with
      leukopenia who received cyclophosphamide (CPA). When CPA (30 mg/kg per d) was
      administered intravenously, the total blood leukocyte count decreased to levels
      below 5000/microliters approximately 4 d after the initiation of CPA multiple
      dosing. The decreased level of the total blood leukocyte count was maintained
      throughout the period of CPA dosing. RhG-CSF was given once a day for 3 d in CPA
      treated rabbits via i.n. administration of aqueous preparations containing rhG
      CSF with or without alpha-cyclodextrin (alpha-CyD). The total blood leukocyte
      count increased from levels below 5000/microliters to the normal physiological
      level following i.n. administration of rhG-CSF preparation and reduced the period
      of leukopenia induced by CPA. The coadministration of rhG-CSF and alpha-CyD was
      more effective in increasing the total blood leukocyte count. It is suggested
      that i.n. administration of rhG-CSF is promising for reducing the risk of
      cytotoxic chemotherapy (CPA)-induced leukopenia as an adverse side effect.

PMID- 8535402
TI  - Time-dependent changes in the pharmacokinetics and renal excretion of xanthine
      derivative enprofylline induced by bacterial endotoxin in rats.
AB  - Time-dependent changes in the pharmacokinetics and renal handling of enprofylline
      induced by bacterial endotoxin (Klebsiella pneumoniae LPS) were investigated in
      rats. To evaluate the early effect of LPS on kidney functions and the renal
      excretion of enprofylline, which is an organic anion drug excreted primarily by
      an active tubular secretion, LPS (250 micrograms/kg) was infused for 5 min under
      constant infusion at rates of 2.3 and 23 micrograms/min/kg for inulin and
      enprofylline, respectively. LPS caused a drop in the glomerular filtration rate
      (GFR), estimated as the renal clearance of inulin, to 65-75% of that observed in
      the control rats within 30 min after the LPS treatment. The renal clearance (CLr)
      of enprofylline decreased in conjunction with GFR, while the percentage of
      decrease in the CLr was slightly greater than that in GFR. LPS-induced decreases
      in the CLr for enprofylline and GFR continued over the testing period of 120 min.
      The time-dependent effect of LPS on the pharmacokinetics of enprofylline was
      examined by a single injection of enprofylline (2.5 mg/kg) to rats pretreated 2,
      10 or 24 h earlier with or without LPS. The pharmacokinetic parameters of
      enprofylline were determined by a model-independent method. Significant changes
      in the systemic clearance for enprofylline were observed in rats pretreated 2 and
      10 h earlier with LPS, but no such changes were observed in rats pretreated 24 h
      earlier with LPS. These findings indicate the existence of a time-dependent
      effect of LPS on the pharmacokinetics of enprofylline, and suggest that LPS at a
      dose of 250 micrograms/kg, at least, does not induce cytotoxicity to kidney
      cells.

PMID- 8535403
TI  - Pharmacokinetic and pharmacodynamic studies of centrally acting drugs in rat:
      effect of pentobarbital and chlorpromazine on electroencephalogram in rat.
AB  - Electroencephalogram (EEG) alterations in rat after the i.v. administration of
      pentobarbital (PTB) and chlorpromazine (CPZ) were measured by power spectral
      analysis. The time courses of PTB concentrations in plasma, cerebrospinal fluid
      (CSF) and brain were determined after the i.v. administration of PTB (20, 40
      mg/kg) by GC-MS. The PTB concentrations in plasma, CSF and brain could be
      described by a biexponential equation, a CSF model and a blood flow limited
      model, respectively. The relationship between the alteration of EEG and the PTB
      concentrations in the CSF or brain or the effect compartment were analyzed using
      the sigmoid Emax model. The alteration of EEG after PTB administration could be
      described by the PTB concentration in these compartments using the sigmoid Emax
      model. These results indicated that the site of action for the alteration of EEG
      after PTB administration is in instantaneous equilibrium with the CSF, the brain
      and the effect compartment. Thus, alterations in EEG after PTB administration can
      be predicted by monitoring the total PTB concentration in plasma. The alteration
      of EEG after i.v. administration of CPZ (4 mg/kg) showed a two-phase variation.
      Although the relationship between the alteration of EEG and the CPZ
      concentrations in CSF or the striatum or the effect compartment (total and free
      drug) were analyzed using the linear model, the Emax model or the sigmoid Emax
      model, the two-phase alteration of EEG after CPZ administration could not be
      described by any of these models. These results indicated that the
      pharmacokinetic and pharmacodynamic modeling of CPZ during the alteration of EEG
      may be complicated due to several pharmacokinetic and pharmacodynamic factors,
      such as an alteration of the free fraction of CPZ in the striatum, the formation
      of active metabolites, and two different intrinsic effects of CPZ on the EEG (one
      in an increase and the other in a decrease of the brain's electrical activity.

PMID- 8535404
TI  - Application of curdlan to controlled drug delivery. II. In vitro and in vivo drug
      release studies of theophylline-containing curdlan tablets.
AB  - Tablets (300 mg) having two different surface areas were prepared from spray
      dried particles of curdlan (100 mg)/theophylline(200 mg). Drug release from the
      tablets was studied in vitro and in vivo. The in vitro drug release from a tablet
      with a larger surface area (Tab L) was faster than that with a smaller one (Tab
      S). The water uptake of Tab L was larger than that of Tab S, probably due to the
      difference in the tablets' surface areas. However, the water uptake was not a
      rate-determining step for the drug release from curdlan tablets containing a
      large amount of theophylline. A straight line was obtained when release % was
      plotted vs. time. The slope of each curve was calculated as 0.59 for Tab L and
      0.58 for Tab S. This indicates that the release mechanism is non-Fickian
      diffusion controlled. In addition, the curdlan tablets or theophylline powder
      were administered orally to 5 healthy volunteers, and saliva concentrations of
      theophylline were determined. Each saliva concentration was converted to plasma
      concentration using the saliva to plasma ratio of the drug in each subject. The
      AUC of Tab L was nearly the same as that of powder, while the AUC of Tab S was
      smaller than that of powder. The mean residence times (MRTs) of theophylline
      powder, Tab S and Tab L were 11.1 +/- 1.5, 25.4 +/- 6.3 and 17.1 +/- 1.5 h (N = 4
      5, mean +/- S.D.), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535405
TI  - Synergistic anti-tumor effects of mitomycin C and bile salts against L1210 cells.
AB  - The effects of various adjuvants on the cytotoxicity of mitomycin C (MMC) were
      studied in L1210 mouse leukemia cells. Adjuvants examined in this study were
      sodium glycocholate (Na-GC), sodium deoxycholate (Na-DC), O-n-dodecyl-beta-D
      maltopyranoside (LM), and sodium salicylate. Among various additives, bile salts
      such as Na-GC and Na-DC were the most effective for increasing the cytotoxicity
      of MMC against L1210 cells. A dose-dependent increase in cytotoxic effect of MMC
      was observed in the presence of these bile salts. To elucidate a possible
      mechanism for enhancing the cytotoxic effect of MMC by the bile salts, the
      cellular uptake of MMC with or without Na-GC was examined using L1210 cells. The
      cellular concentration of MMC was determined by a reversed-phase HPLC. When Na-GC
      was coadministered with MMC, the uptake of MMC into L1210 cells was significantly
      enhanced as compared with MMC alone. Furthermore, the membrane fluidity of L1210
      cells, as determined by fluorescence polarization, was increased in the presence
      of Na-GC. These results suggested that the enhancement of cytotoxicity of MMC by
      the addition of Na-GC could be attributed to the increasing cellular uptake of
      MMC due to the increasing membrane fluidity of L1210 cells.

PMID- 8535406
TI  - Pharmacokinetics of SN-38 [(+)-(4S)-4,11-diethyl-4,9-dihydroxy-1H-
      pyrano[3',4':6,7]-indolizino[1,2-b]quinoline-3,14(4H,12H)-dione], an active
      metabolite of irinotecan, after a single intravenous dosing of 14C-SN-38 to rats.
AB  - Irinotecan (CPT-11) is a camptothecin derivative used for the treatment of
      cancer. It is a prodrug that is metabolized to its active form, SN-38 [(+)-(4S)
      4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]- indolizino[1,2-b]quinoline
      3,14(4H,12H)-dione]. To clarify the pharmacokinetic difference between CPT-11 and
      SN-38, the plasma levels, tissue distribution and excretion of SN-38 were
      investigated after dosing rats with 14C-labeled SN-38. The plasma radioactivity
      showed bi-exponential decay with a terminal half-life of 9.91 h. TLC separation
      revealed that the plasma radioactivity consisted mainly of SN-38 at 5 min after
      dosing; however, it was soon replaced with SN-38 glucuronide (SN-38 Glu) and an
      unknown metabolite (M-2). The half-life of unchanged SN-38 after dosing with SN
      38 was about 7 min, which was much shorter than that after dosing with CPT-11
      (2.8 h) as reported previously. Its radioactivity was excreted mainly in feces
      (70.0% within 168 h), and biliary excretion (64.1% within 48 h) could account for
      the fecal excretion. The major component of urinary and biliary radioactivity was
      found by TLC to be SN-38. Whole body autoradiograms revealed that the tissue
      distribution of the radioactivity was low except in the liver and kidney. The
      radioactivity decreased rapidly and little was found in the body 24 h after
      dosing. In conclusion, SN-38 was excreted rapidly from bile and showed poor
      tissue distribution. These characteristics lead to a shorter SN-38 half-life,
      more so than dosing with CPT-11.

PMID- 8535407
TI  - On the inhibitory effect of C17-sulfoconjugated catechol estrogens upon lipid
      peroxidation of rat liver microsomes.
AB  - The antioxidant effect of C17-sulfoconjugated catechol estrogens was examined
      under ascorbic acid- or NADPH-dependent lipid peroxidation in rat liver
      microsomes and compared with that of various estrogens and alpha-tocopherol.
      Among the estrogens tested, a free catechol estrogen such as 4-hydroxyestradiol
      showed the strongest effect, followed by 2-hydroxyestradiol, 2-methoxyestradiol
      and estradiol. Next to these steroids, 2-hydroxyestradiol 17-sulfate, followed by
      4-methoxyestradiol, 4-hydroxyestradiol 17-sulfate and estrone also showed a
      strong inhibitory effect, which was greater than that of alpha-tocopherol. Among
      the C17-sulfates, the guaiacols (2- and 4-methoxyestradiol 17-sulfate) showed a
      slightly lower effect than alpha-tocopherol, but estradiol 17-sulfate had almost
      no effect. The antioxidant activity observed in phenolic or guaiacol steroids was
      considered to be attributed to the catechols produced by their 2- (or 4
      )hydroxylation or their O-demethylation, respectively, during the incubation.
      This was confirmed by identification of the catechols produced from phenolic or
      guaiacol estrogens and even from the estrogen C3-sulfates. The mechanism of the
      inhibition by catechols on lipid peroxidation was speculated to involve their
      activity as radical scavengers, because of their strong reducing activity for 1,1
      diphenyl-2-picrylhydrazyl. The above results suggest that C17-sulfoconjugated
      catechol estrogens (2- and 4-hydroxyestradiol 17-sulfate), although with slightly
      lower activity than their free catechols, are promising endogenous antioxidants.
      The physiological role of these estrogen conjugates during pregnancy is
      discussed.

PMID- 8535408
TI  - Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM), a metal complex with
      selective NADH-dependent reduction by complex I in brain mitochondria: a
      potential radiopharmaceutical for mitochondria-functional imaging with positron
      emission tomography (PET).
AB  - The reductive retention mechanism of copper(II)-pyruvaldehyde-bis (N4
      methylthiosemicarbazone) (Cu-PTSM), a generator-produced positron-emitting 62Cu
      labeled radiopharmaceutical, was studied with non-radioactive and radioactive
      copper. Changes in the chemical form of Cu-PTSM were detected by electron spin
      resonance spectrometry (ESR) with cold copper. The effects of electron transport
      chain inhibitors on the reduction of Cu-PTSM were also examined. Rotenone and
      antimycin A activated the reduction of Cu-PTSM in the brain mitochondria by 1.6-
      and 1.4-fold, respectively, compared with untreated controls, while
      thenoyltrifluoroacetone (TTFA) had no effect on the reduction. These results were
      confirmed with radioactive copper. Furthermore, this reduction of Cu-PTSM was
      dependent on the protein concentration of mouse brain submitochondrial particle
      (SMP) with 1 mM NADH (0 mg-protein/ml: 1.8 +/- 2.5%, 8 mg-protein/ml: 69.0 +/-
      5.5%, each value was % of reduced Cu). Similarly, this reduction depended on NADH
      concentration at a fixed concentration of SMP (8 mg-protein/ml). These results
      indicated that the electron transport chain, especially complex I, participated
      in the reduction of Cu-PTSM in brain mitochondria, and this suggested that Cu
      PTSM has the potential to act as a functional imaging agent for diagnosis of the
      electron transport chain.

PMID- 8535409
TI  - Determination of D-amino acids in serum from patients with renal dysfunction.
AB  - D-Ala and D-Ser were detected in the sera of both normal subjects and patients
      with renal dysfunction, and their concentrations were higher in the patients than
      in the normal subjects. A positive correlation between the concentration of D-Ala
      or D-Ser and that of creatinine (r = 0.733, p < 0.001 or r = 0.634, p < 0.001) or
      blood urea nitrogen (BUN) (r = 0.449, p < 0.05 or r = 0.629, p < 0.001) was
      observed in sera from 20 patients with renal dysfunction. The fraction (%D) of D
      Ala in the total Ala in serum ([D/(D+L)] x 100) correlated well with the
      concentration of creatinine (r = 0.811, p < 0.001), suggesting that it is a
      candidate as a marker for renal proximal tubular dysfunction. The correlations of
      %D of Ser with creatinine and BUN levels were 0.796 (p < 0.001) and 0.919 (p <
      0.001), respectively, indicating that %D of Ser may reflect protein turnover or
      catabolism in certain tissues as well as renal proximal tubular dysfunction.

PMID- 8535410
TI  - Characterization of partially purified alpha-glucosidase in the insoluble
      fraction of bovine crystalline lens.
AB  - Two fractions of neutral alpha-glucosidase were partially purified from the
      insoluble fraction of bovine lens. This is the first report of such an event to
      the best of our knowledge. The apparent native molecular weights of these
      fractions were 121 kDa (fraction-I) and 254 kDa (fraction-II). Both fractions
      contained three polypeptides with molecular weights of 21, 25 and 30 kDa,
      although the proportion of these peptides was different in both fractions. The
      optimal pH of fraction-I and fraction-II was pH 6.0 and 6.5, and the optimal
      temperature for both fractions was approximately 50 degrees C. The Km values of
      fractions-I and -II for 4-methylumbelliferyl-alpha-glucopyranoside were 0.086,
      and 0.192 mM. The activities of these enzymes were inhibited strongly by HgCl2
      and slightly by D-iodoacetic acid, but not by D-turanose. From this, we suggest
      that the enzyme in the insoluble fraction of bovine lens may be a cytoplasmic
      neutral alpha-glucosidase which binds to the cell membrane.

PMID- 8535411
TI  - Involvement of CYP2C in the metabolism of cannabinoids by human hepatic
      microsomes from an old woman.
AB  - The hepatic microsomal metabolism of cannabinoids was studied using the liver
      from an old woman. delta 8-Tetrahydrocannabinol, delta 9-tetrahydrocannabinol and
      cannabinol were biotransformed to their respective 11-hydroxy metabolites by a
      microsomal fraction with specific activities (pmol/min/mg protein) of 29.1, 47.1
      and 27.9, respectively. In addition, both 11-oxo-delta 8-tetrahydrocannabinol and
      11-oxo-delta 9-tetrahydrocannabinol were metabolized to the corresponding
      carboxylic acids with the microsomes. An antibody against mouse CYP2C29 almost
      completely inhibited 11-hydroxylation of the cannabinoids and microsomal aldehyde
      oxygenase (MALDO) activity for 11-oxo-delta 8-tetrahydrocannabinol and 11-oxo
      delta 9-tetrahydrocannabinol, used as substrates, whereas an antibody against rat
      CYP3A2 conversely stimulated the 11-hydroxylation of delta 8-tetrahydrocannabinol
      and MALDO activity for 11-oxo-delta 8-tetrahydrocannabinol. The results indicate
      that a member of CYP2C is primarily responsible for the metabolism of the above
      cannabinoids in the human hepatic microsomes.

PMID- 8535412
TI  - Induction of cytochrome P450 3A (CYP 3A) by E 5110, a non-steroidal anti
      inflammatory agent (NSAID), and typical CYP 3A inducers in primary cultures of
      dog hepatocytes.
AB  - First, the effect of E 5110, a non-steroidal anti-inflammatory agent (NSAID), on
      cytochrome P450 subfamilies in dog hepatocyte culture was examined. E 5110 has
      been shown to cause a drug interaction in dogs and humans via induction of
      cytochrome P450 3A (CYP 3A). When dog hepatocytes were cultured for 72 h in the
      presence of 2-30 microM E 5110, the activity levels of ethoxycoumarin O
      deethylase (ECOD) and testosterone 6 beta-hydroxylase (6 beta-OH-T) rose dose
      dependently. Subsequent Western blot analysis of microsomes from hepatocyte
      cultures indicated the presence of higher amounts of CYP 2B and 3A proteins than
      those of the control. Next, the P450 inducing potency of E 5110 was compared with
      those of phenobarbital, rifampicin, phenytoin and carbamazepine, which induce CYP
      3A in human subjects and human hepatocyte cultures. E 5110 was found to be nearly
      as effective as phenytoin, but less potent than rifampicin, on the basis of 6
      beta-OH-T induction.

PMID- 8535413
TI  - Kinetic study on the inhibition of acetylcholinesterase by 1-benzyl-4-[(5,6
      dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (E2020).
AB  - E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride)
      is currently being developed as a treatment for senile dementia of the Alzheimer
      type. Its mechanism of action is to increase central cholinergic activity by
      inhibiting acetylcholinesterase (AChE) in the brain. In this study, the kinetics
      of the inhibitory action of E2020 on AChE was examined in comparison with its
      derivatives (2A1050 and 2A1034) and the reference compound
      tetrahydroaminoacridine (THA) all of which have a similar action. Analysis of the
      data using Lineweaver-Burk plots shows that inhibition by the test compounds fell
      into the category of mixed type. Inhibitor dissociation constants for the free
      enzyme (KI) and acetyl-enzyme (KI) of E2020 are one or two orders of magnitude
      lower than those of 2A1050, 2A1034 and THA. These findings indicate the strong
      inhibitory effect of E2020 on AChE.

PMID- 8535414
TI  - Studies of cuticle drugs from natural sources. III. Inhibitory effect of Myrica
      rubra on melanin biosynthesis.
AB  - The inhibitory effect of a 50% ethanolic extract obtained from the dried leaves
      and the bark of Myrica rubra, was investigated in vitro on melanin biosynthesis
      which is closely related to hyperpigmentation. These extracts inhibited
      tyrosinase activity which converts dopa to dopachrome in the biosynthetic
      process. Furthermore, the extracts inhibited the production of melanin from
      dopachrome by autoxidation and also showed superoxide dismutase (SOD)-like
      activity. After bioassay-guided fractionation, quercetin, myricetin and myricetin
      3-O-rhamnoside were isolated from the leaves. As they showed the inhibitory
      effect on tyrosinase activity, the activity is partially attributable to them in
      the extract of M. rubra. These results suggested that the leaves or the bark of
      M. rubra might be used as a whitening agent for the skin.

PMID- 8535415
TI  - Thermally gelling poloxamine Synperonic T908 solution as a vehicle for rectal
      drug delivery.
AB  - Thermally reversible gels of the block copolymer, Synperonic T908, have been
      evaluated as vehicles for the rectal administration of indomethacin. Prolonged
      plasma levels of indomethacin following rectal administration in such gels was
      observed with the 40% w/w Synperonic T908 gels when compared with commercial
      suppositories. The release rate decreased with an increase in gel concentration
      over the range 30% to 40% w/w. Histological observation showed no damage to the
      rectal mucosal membrane in animals at 6 h after the administration of a 40% w/w
      gel.

PMID- 8535416
TI  - Application of curdlan to controlled drug delivery. III. Drug release from
      sustained release suppositories in vitro.
AB  - The use of curdlan, a natural beta-1,3-glucan, in the preparation of sustained
      release suppositories was studied in vitro. To prepare the suppositories,
      indomethacin, prednisolone or salbutamol sulfate was mixed with curdlan gel.
      Preparation conditions, including heating time and curdlan concentrations of 5
      and 10%, had little effect on the drug release. The tonicity (hypotonic or
      isotonic) of the media for the suppository preparation and for in vitro drug
      release study also had little effect on drug release. However, the heating
      temperature during gel preparation, the drug amount in the suppository and the
      type of release media did affect drug release. It was found that drug release was
      sustained and diffusion-controlled in the three drugs. And finally, curdlan can
      be applicable for use in a sustained release suppository.

PMID- 8535417
TI  - Effect of senegin-II on blood glucose in normal and NIDDM mice.
AB  - The hypoglycemic effect of senegin-II, the main component of Polygala senega
      (Polygalaceae), was examined in normal and KK-Ay mice, one of the model animals
      of non-insulin-dependent diabetes mellitus (NIDDM). Senegin-II (2.5 mg/kg)
      reduced the level of blood glucose in normal mice from 220 +/- 8 to 131 +/- 5
      mg/dl 4 hours after intraperitoneal administration (P < 0.001), and also
      significantly lowered the blood glucose of KK-Ay mice from 434 +/- 9 to 142 +/- 6
      mg/dl under similar conditions (P < 0.001).

PMID- 8535418
TI  - Identification of N4-(2-propenal)spermidine as a major reaction product of
      malondialdehyde and spermidine.
AB  - The reactivity of malondialdehyde(MDA) with spermidine at the physiological pH
      was considerably higher than that with putrescine, glycine, lysine, methylamine
      or dimethylamine, and the major reaction product of MDA-spermidine adduct was
      identified as N4-(2-propenal)spermidine.

PMID- 8535419
TI  - Properties of trichosporin-B-VIa-induced catecholamine secretion from bovine
      adrenal chromaffin cells.
AB  - Trichosporin (TS)-B-VIa, a peptide consisting of 19 amino acid residues and an
      amino alcohol, causes Ca(2+)-dependent secretion of catecholamines from bovine
      adrenal chromaffin cells. The TS-B-VIa-induced secretion was greater under
      alkaline conditions and at a temperature of 37 degrees C compared with that at 21
      degrees or 30 degrees C. It was not observed when the peptide was eliminated from
      the incubation medium. These results strongly suggest that the stimulatory effect
      of TS-B-VIa on the secretion is reversible and dependent on the temperature and
      pH of the incubation medium.

PMID- 8535420
TI  - Spontaneous transfer of viral protein from membrane of influenza virus-infected
      cells to liposomes is dependent on the diameter of receiver.
AB  - Spontaneous transfer of protein from either influenza virus-infected or
      uninfected cells to dimyristoylphosphatidylcholine (DMPC) liposomes was examined.
      The amount of transferred protein of liposomes incubated with influenza virus
      infected cells (I-lipo) was more than that of liposomes incubated with uninfected
      cells (U-lipo). The ratio of the amount of spontaneous transferred protein of I
      lipo to that of U-lipo increased in proportion to the diameter of liposomes
      except for small unilamellar vesicles.

PMID- 8535421
TI  - Distribution of 239,240Pu and 238Pu concentrations in sediments from the Ob and
      Yenisey Rivers and the Kara Sea.
AB  - The major sources of plutonium isotopes in the environment are from nuclear
      weapons testing via global and close-in (debris) fallout, nuclear fuel
      reprocessing and fabrication plant effluents. Measurements of differences in the
      Pu isotopic ratios (239Pu/240Pu, 238Pu/239,240Pu and 241Pu/239,240Pu) have
      yielded information not only on the time horizons for sedimentary deposits but
      also on the sources of Pu. We have measured 238Pu, 239,240Pu and 137Cs
      concentrations in the surficial sediments of the Ob and Yenisey Rivers (Russia)
      and the Kara Sea. The downcore variations of 238Pu and 239,240Pu concentrations
      have also been measured in some sediment cores. A comparison of the sediment core
      inventories of 239,240Pu along with the 238Pu/239,240Pu activity ratios with
      those expected from global fallout at the study sites allows us to estimate the
      relative amounts of reactor-derived 238Pu and 239,240Pu from the dumped reactor
      sites in the study area. In surficial sediment samples, the 239,240Pu
      concentrations vary between 9.4 and 627 mBq kg-1, with a mean of 250 mBq kg-1.
      The 238Pu/239,240Pu activity ratios vary between 0.009 and 0.065 with an average
      value of 0.034 +/- 0.003. This range can be compared to the average
      238Pu/239,240Pu activity ratio of 0.030 for the year 1993 from nuclear weapons
      testing and SNAP fallout obtained from soil studies, indicating very little
      additional sources of 238Pu to the sediments in the study area. In sediment
      cores, the maximum depths at which 239,240Pu was detected varied between 6 and 12
      cm. These depths yield average apparent sedimentation rates in the coastal Kara
      Sea between 1.5 and 3.0 mm yr-1 (assuming Pu input since 1952, and no sediment
      mixing).

PMID- 8535422
TI  - Environmental plutonium in humans.
AB  - Although the current world inventory of plutonium is overwhelmingly man-made, it
      is important to recognize that 244Pu was a primeval radioelement and that 239Pu
      is formed continuously by spontaneous fission of 238U; the atom ratio U:Pu being
      about 10(11):1. It has been calculated that the human body has always carried a
      base load of, perhaps 10(3)-10(5) atoms (< 0.2 amol) of natural plutonium. Since
      1945, the release of 239Pu into the environment from atmospheric nuclear weapons
      testing has added to this base load a civilization-related load which, at
      approximately 300 fmol, is at least 5 orders of magnitude greater. Within the
      human body plutonium is deposited mainly in the liver and skeleton where it
      appears to be retained tenaciously with half-times of many years. Based on 1970
      1980 levels, environmental plutonium may give rise to alpha-particle radiation
      doses of approximately 3-7 microSv/a in human bone and approximately 10-20
      microSv/a in liver, doses which from our present understanding of the radio-and
      chemical toxicity of plutonium are far too small to cause any recognizable health
      effects.

PMID- 8535423
TI  - Transuranics in bone of deceased former residents of Rongelap Atoll, Marshall
      Islands.
AB  - Rongelap Atoll received intensive fallout from the 1 March 1954 Bravo
      thermonuclear test 105 miles upwind at Bikini. Fearful of their continued
      exposure to radiation, the residents of Rongelap Atoll went into voluntary exile
      in 1985. Transuranic soil concentrations on Rongelap Island are about 2-3 orders
      of magnitude greater than the average for the Northern hemisphere; the three
      dominating transuranics are 239,240Pu and 241Am. Only conflicting information has
      been available about the extent of transuranic uptake by the Rongelap community.
      As part of the Rongelap Resettlement Project, the community endorsed the
      exhumation of bones of deceased former atoll residents to provide an independent
      estimate of plutonium intake. This approach has the advantage of reducing the
      uncertainties associated with pathway modeling and the interpretation of urine
      data. Six graves (4 adults, 2 children) were selected for exhumation. Femora and
      tibiae were selected as well as humeri from the children's graves. The rest of
      the remains was left undisturbed. The results of the analysis of 239,240Pu and
      241Am are presented. Assuming that the data can be considered as representative
      for the Rongelap population as a whole, the contamination with transuranics on
      Rongelap Atoll appears to result in radiation exposures in the order of 1% of the
      compliance limit of 100 mrem (1 mSv) effective dose equivalent per year.

PMID- 8535424
TI  - Assessment of plutonium exposures in Rongelap and Utirik populations by fission
      track analysis of urine.
AB  - A nuclear device, code-named Bravo, detonated at Bikini Atoll at 6:45 a.m. on 1
      March 1954, unexpectedly released a large amount of radioactivity. Over 40 years
      after this incident, the study of its impact on the radiological health and
      environmental safety of the residents of Rongelap and Utirik Atolls continues. In
      1987, researchers at Brookhaven National Laboratory established a fission track
      analysis (FTA) method for low-level 239Pu urinalysis. Two years later, a new
      shipboard protocol was developed for collecting 24-h radiologically clean urine
      samples. The purpose of this paper is to update information on the FTA method for
      measuring low-levels of plutonium, and to summarize results on the distribution
      of 239Pu in the populations of Rongelap and Utirik between 1981-1991. Plutonium
      detection levels (99% confidence level) in these samples were 2-3 microBq, which
      is equivalent to 0.2-0.3 mSv effective dose equivalent (EDE) to age 70 for
      Marshallese. The latest 1991 FTA data indicate average EDE of 0.62 mSv and 1.6
      mSv for the people of Rongelap and Utirik, respectively, which both are the
      highest values since 1988.

PMID- 8535425
TI  - Introduction: perspectives in HIV care: a view from the front lines.

PMID- 8535426
TI  - A journey through the epidemic.

PMID- 8535427
TI  - A view from the front lines of bioethics.

PMID- 8535428
TI  - The challenge of treating gay men with AIDS.

PMID- 8535429
TI  - Caring for HIV-infected drug users: a provider's perspective.

PMID- 8535430
TI  - Understanding the needs of children.

PMID- 8535431
TI  - HIV-infected health care workers. The personal impact.

PMID- 8535432
TI  - HIV-infected health care workers. The legal perspective.

PMID- 8535433
TI  - Supporting and advocating for HIV-positive health care workers.

PMID- 8535435
TI  - Historical and analytical overview of policy issues affecting women living with
      AIDS: a blueprint for learning from our past.

PMID- 8535434
TI  - AIDS and politics: death and taxes.

PMID- 8535436
TI  - The provider as advocate.

PMID- 8535437
TI  - Miles to go before we sleep.

PMID- 8535438
TI  - Molecular genetics of the glycophorin gene family, the antigens for MNSs blood
      groups: multiple gene rearrangements and modulation of splice site usage result
      in extensive diversification.
AB  - The purpose of the review is to describe a system of human erythrocyte membrane
      glycoproteins exhibiting extensive diversity. Glycophorins A and B (GPA and GPB)
      are the antigens of the MNSs blood groups; thus individuals bearing variant
      glycophorins can be readily identified by serological typing. Examination of the
      wide array of variants of these antigens showed that they include many forms,
      possibly made evident by lack of constraints due to the apparent dispensability
      of the parent molecules. This article reviews the molecular genetics of 25
      variants of the glycophorin gene family, whose common denominator is that they
      arise from unequal gene recombinations or gene conversions coupled to splice-site
      mutations. Most rearrangements occurred within a 2-kb region mainly within GPA
      and GPB of the gene family and only rarely within the third member, GPE. The key
      feature is the shuffling of sequences within two specific exons (one of which is
      silent), homologous in the two parent genes. This has resulted in expression of a
      mosaic of sequences within this region, leading to polymorphism. The common
      pattern of recombinations coupled to pre-mRNA splicing was the predominant
      mechanism of the origin of glycophorin diversity. Thus far this mechanism appears
      to be unique among human gene families. It could have occurred by chance
      rearrangements among closely linked genes and been driven by a biological
      advantage, not as yet identified. This remains to be established. Nevertheless,
      gene rearrangements observed here are akin to those reported for the major
      histocompatibility complex (MHC). In the glycophorin family the small size of the
      region within which gene interactions have occurred and the participation of
      essentially only two alleles makes this relatively simpler system more focused
      and easier to dissect and describe molecularly.

PMID- 8535439
TI  - Molecular basis of hereditary fructose intolerance: mutations and polymorphisms
      in the human aldolase B gene.
AB  - Mutations in the human aldolase B gene that result in hereditary fructose
      intolerance have been characterized extensively. Although the majority of
      subjects have been from northern Europe, subjects from other geographical regions
      and ethnic groups have been identified. At present 21 mutations have been
      reported; 15 of these are single base substitutions, resulting in nine amino acid
      replacements, four nonsense codons, and two putative splicing defects. Two large
      deletions, two four-base deletions, a single-base deletion, and a seven-base
      deletion/one-base insertion have been found. This last mutation leads to a defect
      in splicing and it is likely that one of the small deletions does as well.
      Regions of the enzyme where mutations have been observed recurrently are encoded
      by exons 5 and 9. Indeed, the three most common mutations are found in these
      exons. Two of these prevalent HFI mutations arose from a common ancestor and
      spread throughout the population by genetic drift. This finding was based on
      linkage to two sequence polymorphisms, which are among very few informative
      polymorphic markers that have been identified within the aldolase B gene. Because
      of the prevalence of a few HFI alleles, and the recent advances in molecular
      methods for identifying and screening for mutation, the diagnosis of HFI by
      molecular screening methods should become routine. These molecular diagnostic
      methods will be extremely beneficial for this often difficult to diagnose and
      sometimes fatal disease.

PMID- 8535440
TI  - Pancreatic insufficiency and pulmonary disease in German and Slavic cystic
      fibrosis patients with the R347P mutation.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis
      transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated
      chloride channel. The R347P is a missense mutation located within the first
      membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an
      overall worldwide frequency of about 0.2%. The patients, originally described
      with this mutation were compound heterozygotes with the delta F508 mutation and
      had a very mild course of CF, suggesting that R347P, similar to other missense
      mutations affecting the MSD1 domain, causes a mild phenotype. We report here a
      group of 19 CF patients with the R347P mutation of German, Bulgarian, Czech, and
      Slovak origin, including two homozygotes. Most patients presented with early
      disease onset, pancreas insufficiency (PI), and early pulmonary involvement,
      suggesting that this mutation can lead to a severe course of CF. Most R347P
      alleles in the group studied share a common polymorphic haplotype. In addition,
      these analyses gave evidence for recurrence of the mutation in two CF patients of
      German and Czech origin.

PMID- 8535441
TI  - Comparison between medium-chain acyl-CoA dehydrogenase mutant proteins
      overexpressed in bacterial and mammalian cells.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially lethal
      inherited defect in the beta-oxidation of fatty acids. By comparing the behaviour
      of five missense MCAD mutant proteins expressed in COS cells and in Escherichia
      coli, we can define some of these as "pure folding mutants." Upon expression in
      E. coli, these mutant proteins produce activity levels in the range of the wild
      type enzyme only if the chaperonins GroESL are co-overproduced. When
      overexpressed in COS cells, the pure folding mutants display enzyme activities
      comparable to the wild-type enzyme. The results suggest that the MCAD mutations
      can be modulated by chaperones, a phenomenon that may influence the manifestation
      of the MCAD disease.

PMID- 8535442
TI  - Allele-specific associated polymorphism analysis: novel modification of SSCP for
      mutation detection in heterozygous alleles using the paradigm of resistance to
      thyroid hormone.
AB  - Allele-specific polymorphism (ASAP) analysis is a modification of single-strand
      conformation polymorphism (SSCP) mutation screening under optimized temperature
      conditions in a minigel format with ethidium bromide detection. ASAP analysis was
      used to screen for and identify mutations within the human thyroid hormone
      receptor-beta (hTR-beta) gene. These mutations are the underlying cause of
      resistance to thyroid hormone (RTH). Eleven dissimilar known hTR-beta mutations
      and six previously uncharacterized mutations were accurately identified. ASAP
      screening extends to unique ASAP-DNA fingerprinting as an identifying signature
      for each novel hTR-beta mutation detected thus far. Gel-plugs from the SSCP gels
      containing polymorphic single-stranded DNA alleles were used without elution to
      prepare solid-phase sequencing templates for mutant allele PCR and sequencing
      (MAPS). The coupling of ASAP analysis with MAPS has eliminated many of the
      interpretative and technical problems associated with the sequencing of
      heterozygous alleles. Together, this convenient screening and sequencing
      methodology offers accuracy, reproducibility, speed, and the potential
      elimination of all radioactivity, providing a general strategy for future
      automated detection and characterization of genetic mutations.

PMID- 8535443
TI  - Rapid restriction fragment analysis for screening four point mutations of the low
      density lipoprotein receptor gene in French Canadians.
AB  - Familial hypercholesterolemia (FH) has an estimated frequency of 1:154 among
      French Canadians in Northeastern Quebec, compared with 1:500 in most other
      populations. FH is caused by numerous mutations of the low-density lipoprotein
      (LDL) receptor gene, but only six well-characterized mutations are known to cause
      FH in French Canadians. High prevalence of the phenotype, along with a limited
      number of mutations in this population, provides a unique opportunity to study
      genotype-phenotype variation. Since the current methods for detection of point
      mutations in this population use complicated approaches, we report polymerase
      chain reaction (PCR)-based restriction fragment analysis to detect all four point
      mutations. This approach provides a rapid diagnosis and is suitable to screen
      large number of samples for studies in genetic epidemiology; it should be useful
      in identifying FH in other populations bearing the same mutations.

PMID- 8535444
TI  - Novel missense mutation in the phenylalanine hydroxylase gene leading to complete
      loss of enzymatic activity.

PMID- 8535445
TI  - Mutations Ivs4nt1, 47delCT, and G148S identified in the phenylalanine hydroxylase
      gene by RT-PCR of illegitimate transcripts and chemical cleavage of mismatch.

PMID- 8535446
TI  - Novel seventeen basepair deletion in exon 3 of the beta-globin gene.

PMID- 8535447
TI  - Three novel mutations in the EGF precursor homology domain of the low-density
      lipoprotein receptor gene in Northern Irish patients with familial
      hypercholesterolemia.

PMID- 8535448
TI  - Missense mutation (Arg121Trp) in the Norrie disease gene associated with x-linked
      exudative vitreoretinopathy.

PMID- 8535449
TI  - A 48-bp insertion between exon 13 and 14 of the HEXB gene causes infantile-onset
      Sandhoff disease.

PMID- 8535450
TI  - Partial deletions of putative adrenoleukodystrophy (ALD) gene in Japanese ALD
      patients.

PMID- 8535451
TI  - A 931 + 2T-->C transition in one COL1A2 allele causes exon 16 skipping in PRO
      alpha 2(I) mRNA and produces moderately severe OI.

PMID- 8535452
TI  - Two intronic mutations in the adrenoleukodystrophy gene.

PMID- 8535453
TI  - A novel mutation (P316L) in a female with pyruvate dehydrogenase E1 alpha
      deficiency.

PMID- 8535454
TI  - Two novel missense mutations (E654K, L396P) in Caucasian patients with
      myophosphorylase deficiency (McArdle's disease).

PMID- 8535455
TI  - Funding for urolithiasis research: progress and strategies for future NIH
      support.
AB  - A review of the National Institutes of Health funding history for urolithiasis
      shows that support has increased from about $3 million in 1990 to about $4.7
      million in 1993 and to an estimated $5.1 million in 1994. The award of large
      project grants accounts for the increase: individual research project grant
      funding (R01-type grants) has not increased. The overall funding for urologic
      research supported by the National Institute of Diabetes and Digestive and Kidney
      Diseases has more than doubled in this same period, with most of the increase
      attributable to the award of individual research grants. Although there has been
      a significant number of urolithiasis research grant applications submitted in
      this time period, the percent of successful (funded) applications continues to
      lag behind the number in other urology-related areas. Strategies for improving
      the award rate for urolithiasis-related research grant applications are reviewed.

PMID- 8535456
TI  - Shockwave lithotripsy and pacemakers: experience with 20 cases.
AB  - Lithotripsy treatment of urinary tract calculi initially excluded patients with
      cardiac pacemakers. Continued research and clinical study of patient outcomes has
      promoted a change in that initial concept. The Oklahoma Lithotripsy Center has
      successfully treated 20 patients with various types of pacemakers. No significant
      cardiovascular events occurred during treatment. Patients should be evaluated
      before the procedure by a cardiologist, and dual-chamber pacemakers should be
      reprogrammed to the single-chamber mode. Patients who cannot tolerate this should
      not undergo SWL. Rate-responsive pacemakers should be programmed to the non-rate
      responsive (VVI) mode. The pacemaker should be at least 5 cm from the blast path.
      With these precautions and careful monitoring, SWL can be performed safely in
      most patients with pacemakers.

PMID- 8535457
TI  - Reduction of urinary stone recurrence by dietary counseling after SWL.
AB  - To reduce the recurrence rate of or urolithiasis, dietary counseling was
      conducted for calcium-stone patients. Sixty-six patients received dietary
      counseling and were in principle instructed to use the Recommended Dietary
      Allowance for Japanese as their goal. Seventy-three patients did not undergo the
      counseling. Comparison of the dietary intake of the patients with the dietary
      requirements for Japanese revealed that protein intake, especially animal protein
      intake, was higher and calcium intake lower in the patients. As a result of the
      counseling, intakes of total protein, animal protein, fat, and carbohydrates were
      all reduced. Patients in the stone recurrence-free group excreted less oxalate
      than those in the recurrent one. The excretion of oxalate was then reduced and
      urine volume increased owing to the diet counseling program. The stone recurrence
      rate of the group participating in the diet counseling was lower than that of the
      group not taking part. The recurrence rate of the hyperoxaluric group was higher,
      with statistical significance, than that of the normooxaluric group among those
      not receiving the dietary counseling. With dietary counseling, the recurrence
      rate significantly decreased in the hyperoxaluric patients. Thus, the reduction
      in the rate of stone recurrence resulting from participation in the diet
      counseling program seemed to be attributable to the decrease in urinary oxalate
      excretion. Dietary counseling seems to be a useful measure to prevent urinary
      stone recurrence.

PMID- 8535458
TI  - Technical tip: use of open-ended guidewire to facilitate laser lithotripsy during
      flexible ureteroscopy.
AB  - You have just passed your flexible ureteroscope to the level of the upper
      ureteral calculus. The stone is in view, but as you advance the laser fiber, it
      fails to exit the ureteroscope. All measures to advance the fiber prove futile.
      Sound familiar? We have found this to be an all too common and frustrating
      situation with the use of the flexible ureteroscope during laser lithotripsy. Our
      review of the literature reveals that this subject has not been adequately
      addressed. We have been successful with the aid of an open-ended 0.035-inch
      guidewire that admits the 320-microns laser fiber.

PMID- 8535459
TI  - Laparoscopic cutaneous ureterostomy: technique for palliative upper urinary tract
      drainage.
AB  - Extensive pelvic carcinomatosis often results in bilateral ureteral obstruction
      and renal parenchymal loss. Percutaneous nephrostomies can be used for palliative
      means but may be poorly tolerated. Laparoscopic techniques can be applied to
      obtain a more permanent urinary diversion. An elderly gentleman with extensive
      pelvic transitional cell carcinoma of the bladder and only one functioning renal
      unit underwent percutaneous nephrostomy tube placement in combination with
      palliative cytoreductive radiation therapy. Poor patient tolerance led to
      repetitive nephrostomy tube replacement. A cutaneous ureterostomy was chosen as a
      more permanent urinary diversion, and laparoscopic techniques allowed this to be
      accomplished expeditiously. At 18 months postoperatively, the patient's unstented
      cutaneous ureterostomy is functioning well, and the serum creatinine
      concentration remains normal.

PMID- 8535460
TI  - Laparoscopic nephrolysis for chyluria: case report of long-term success.
AB  - Laparoscopic nephrolysis was performed in an 81-year-old man with recurrent
      chyluria. A total of five trocars were used for approaching the lymphatic ducts
      over the right ureter and renal hilum. The lymphatic ducts identified were easily
      ligated under laparoscopic magnification. The recovery of this patient was quick
      and uneventful. The follow-up urinalysis for chyle was negative, and his serum
      albumin concentration increased from 3.0 g/dL to 4.2 g/dL at 2 years
      postoperatively. This case report attests to the long-term efficacy of a
      laparoscopic approach to ligation of lymphatic fistulas for the treatment of
      recalcitrant chyluria.

PMID- 8535461
TI  - Intraluminal ultrasound-guided biopsy of the prostate: case report.
AB  - Patients who have undergone proctectomy can present a difficult diagnostic
      challenge for the urologist, as digital rectal examination and transrectal
      ultrasound scanning are not possible. Various methods have been tried to biopsy
      the prostate in patients without rectums and have proved to be limited in their
      usefulness. Intraluminal ultrasound employs a small high-frequency probe that
      creates an image from an intraluminal perspective. We describe a new role for
      this imaging method in which intraurethral intraluminal ultrasound scans can be
      used to guide perineal prostate biopsies in the patient without a rectum.

PMID- 8535462
TI  - Ultrasonographic and pathologic changes in the prostate of patients with benign
      prostatic hyperplasia after transurethral balloon laser therapy.
AB  - Twenty-seven patients with benign prostatic hyperplasia (BPH) were treated with a
      transurethral flexible laser balloon (PROSTALASE) under ultrasound guidance.
      Three months after treatment, 22 (82%) of the patients showed a 50% or greater
      decrease in the AUA Symptom Score. The average uroflow rate, peak uroflow rate,
      and postvoiding residual urine volume also showed significant improvement.
      Ultrasonography showed that the prostatic volume had decreased by 17% (8%-37%).
      Also, a circular hyperechoic zone about 3 cm in diameter was noted around the
      prostatic urethra. The prostatic tissue in the hyperechoic zone was sampled by
      transperineal needle biopsy under transrectal ultrasound guidance, and
      histopathologic examination showed degenerative necrosis. The necrotic tissue was
      gradually absorbed, resulting in prostatic shrinkage at around the third month.
      These results suggest that clinical improvement, both subjective and objective,
      is brought about by this therapy.

PMID- 8535463
TI  - Is there a role for transrectal microwave hyperthermia in the treatment of benign
      prostatic hyperplasia? A critical review of a six-year experience.
AB  - We critically reviewed our 6-year experience with transrectal microwave
      hyperthermia of the prostate for benign prostatic hyperplasia (BPH) in 320
      patients either at high surgical risk or refusing surgery. Transrectal prostatic
      hyperthermia was given in five to ten 60-minute sessions with an intraprostatic
      temperature ranging from 42 degrees to 43.5 degrees C. Although an amelioration
      of symptoms and urodynamic measures was seen initially in most patients, only
      residual urine volume showed a statistically and clinically significant
      improvement at the long-term follow-up. According to maximum flow nomograms,
      bladder outlet obstruction was not resolved by the treatment. We conclude that
      although the transrectal hyperthermia proved to be a safe procedure, it did not
      cure BPH in the long term. Considering the results seen with newer nonsurgical
      procedures such as prostatic stents and prostatic lasers, we believe that
      transrectal hyperthermia should not be recommended to symptomatic BPH patients.

PMID- 8535464
TI  - An accurate technique for detailed prostatic interstitial temperature-mapping in
      patients receiving microwave thermal treatment.
AB  - A minimally invasive prostatic interstitial temperature-mapping technique is
      described that supplies accurate, detailed information on thermal doses delivered
      to precisely localized tissue sites. The technique employs a comparatively large
      numbers of thermosensors, highly accurate placement of those thermosensors at
      specified three-dimensional coordinates, fiberoptic technology that avoids
      significant interaction between the thermosensors and the applied microwave
      field, and continuous temperature readout. Biplane ultrasound imaging and
      fluoroscopy were used to ensure stereotactic accuracy of thermosensor placement.
      The technique was applied in 15 patients with benign prostatic hyperplasia (BPH)
      undergoing a 1-hour microwave thermal treatment session. The thermal mapping
      procedures and microwave treatment were generally well tolerated. The mean
      maximum temperature in the prostate and periprostatic tissue (57.9 +/- 1.9
      degrees C) was significantly higher (P < 0.001) by more than 18 degrees C than
      that in either the urethra (39.6 +/- 0.9 degrees C) or the rectum (40.8 +/- 1.7
      degrees C). In a representative patient, microwave treatment resulted in stable
      elevation of temperature 5 mm radially from the urethra that averaged 66.0 +/-
      0.1 degrees C. At 10 mm from the urethra, the temperature averaged 50.5 +/- 0.1
      degrees C. Urethral and rectal temperatures remained at innocuous levels. In
      conjunction with pathologic studies, this interstitial thermal mapping method
      should prove useful in defining the optimal thermal doses for microwave therapy.
      The method should also find uses in evaluating different microwave treatment
      systems, which can vary markedly in thermal performance, as well as other
      modalities that apply heat to prostatic tissue.

PMID- 8535465
TI  - Epididymo-orchitis after cryoablation of prostate for prostate cancer.
AB  - We report two cases of acute epididymo-orchitis developing 4 to 6 weeks after
      cryoablation for prostate cancer. One patient required a simple orchiectomy for
      epididymal abscess; the other responded to treatment with antibiotics. Since the
      occurrence of these two cases, we routinely perform bilateral vasectomy prior to
      prostate cryoablation. We suggest that an extended course of prophylactic
      antibiotics may also be needed in order to avoid this complication.

PMID- 8535466
TI  - Effect of phonophoresis with dexamethasone on adrenal function.
AB  - One of the side effects of corticosteroid ingestion and inhalants is suppression
      of the adrenal glands. Phonophoresis of topically applied corticosteroids is
      commonly used to treat musculoskeletal inflammatory conditions. The purpose of
      this study was to determine whether phonophoresis with dexamethasone sodium
      phosphate affected adrenal function. The subjects included 28 male volunteers
      (mean = 25.3 years, SD = 6.4) who received phonophoresis to the left shoulder
      every other day for 2 weeks. Subjects were randomly assigned to one of four
      groups, including a control group (N = 8), an ultrasound group (N = 8), a .33%
      dexamethasone group (N = 7), and a ultrasound with .33% dexamethasone group (N =
      5). Adrenal function was assessed by 24-hour urinary-free cortisol (microgram
      cortisol/g creatinine) collected two days prior to and following the
      phonophoresis treatments. A nonparametric analysis of variance using a split plot
      factorial design was calculated for ranked urinary-free cortisol scores and found
      no significant (p > 0.05) differences in urinary-free cortisol levels between the
      four groups and between the four collection days, and there were no significant
      (p > 0.05) interactions exhibited between group and collection day. This study
      suggests that phonophoresis with dexamethasone sodium phosphate, using common
      clinical parameters, does not cause dexamethasone sodium phosphate to become
      systemic in large enough quantities to impair adrenal function.

PMID- 8535467
TI  - The incidence of musculoskeletal injuries in an amateur triathlete racing club.
AB  - The sport of triathlon involves three different endurance sports: swimming,
      biking, and running. Cross-training allows the athlete to train for one sport
      while resting from another. The repetitive motions required for each sport may
      lead to overuse and injury. The purpose of this study was to examine
      musculoskeletal injury incidence in amateur triathletes to determine if these
      injuries caused lost time from training, racing, working, or daily functioning.
      Seventy-two recipients responded to survey items that gathered information about
      demographics, sports participation, and musculoskeletal injury occurrence and
      interference with sports participation, work, and daily activities. Three
      quarters sustained triathlon-related musculoskeletal injuries during training due
      to overuse. A majority experienced training interruption and interference with
      daily functioning and sought professional help for their injuries. Little
      information is available on the treatment of musculoskeletal injuries in
      triathletes. This survey raises important clinical implications for physical
      therapists. Further exploration of overuse injury incidence is warranted in this
      population.

PMID- 8535468
TI  - Relationship of isokinetic peak torque with work and power for ankle plantar
      flexion and dorsiflexion.
AB  - Past research has analyzed the relationship of peak torque with work and power on
      the muscles surrounding the knee with correlation coefficients being reported,
      ranging from .67 to .99. No studies to date have examined this relationship for
      muscles surrounding the ankle joint. The purpose of this study was to analyze the
      relationship of peak torque with work and power for the plantar flexor and
      dorsiflexor muscles of the ankle. Isokinetic data were collected from 15 healthy
      subjects (six males, nine females; mean age = 26.6 years) on an isokinetic
      dynamometer across two trials at speeds of 30 and 120 degrees/sec. The results of
      Pearson product moment correlations between peak torque to work and peak torque
      to power indicated correlation coefficients ranging from .81 to .97 for all
      speeds of testing and angular velocities. These findings suggest that peak torque
      is representative of work and power.

PMID- 8535469
TI  - A review of the McMurray test: definition, interpretation, and clinical
      usefulness.
AB  - Clinicians frequently use the results of clinical diagnostic tests to make
      decisions concerning patients. The intent of this paper is to review the
      technical aspects and measurement properties of the McMurray test and, more
      globally, to illustrate the impact that indiscriminate test application has on
      test interpretation. The literature shows that diagnostic accuracy studies, which
      evaluate the test described by McMurray, yield remarkably similar estimates of
      sensitivity (about 26%) and specificity (about 94%). These test characteristics
      are applied to three case scenarios to illustrate the impact that history
      specific prevalence (i.e., the likelihood a patient has the condition based on
      the history) has on the predictive values. The results show a high false positive
      rate when applied to patients who, based on the history, have a low pre-physical
      examination likelihood for the condition of interest and a higher false negative
      rate when applied to patients who have a high history-specific prevalence.
      Readers are warned that the exhaustive examination approach effectively lowers
      the prevalence and results in a high false positive rate. The impact that the
      exhaustive approach has on increasing the false positive rate is universal to all
      diagnostic investigations and is not unique to the McMurray test.

PMID- 8535470
TI  - Backward walking at three levels of treadmill inclination: an electromyographic
      and kinematic analysis.
AB  - Backward walking on a treadmill is a common tool for lower extremity
      rehabilitation in the clinical setting. The purpose of this study was to evaluate
      the adaptations in the gait cycle produced by walking backward on a treadmill at
      0, 5, and 10% inclination. Sixteen healthy adult subjects (14 females, two
      males), mean age of 23.19 +/- 3.02, participated. Joint positions for hip, knee,
      and ankle were measured during a complete gait cycle. Values were time matched
      with average electromyographic (EMG) activity (surface electrode) of the rectus
      femoris, hamstrings, gastrocnemius, and anterior tibialis during each subphase of
      gait (initial contact, midstance, heel-off, and midswing). Values of joint
      position and average EMG were compared over the three treadmill conditions.
      Subjects walked for approximately 1 minute at 4.0 km/h. A simple repeated
      measures analysis of variance (p < .05) with a Duncan post hoc test was used to
      analyze for changes. Significant changes occurred in the joint positions of the
      knee and ankle at initial contact (ankle increased from 9.81 +/- 5.06 degrees to
      13.08 +/- 3.68 degrees; knee increased from 30.94 +/- 5.25 degrees to 42.42 +/-
      4.08 degrees) as the treadmill was raised from 0 to 10%. Significant changes
      occurred for average EMG activity for each muscle studied over the three
      treadmill conditions. The greatest changes occurred in the gastrocnemius at
      initial contact (increase from 189.76 +/- 44.29% to 293.09 +/- 79.16%) between
      the 0 and 10% conditions. The results of this investigation confirm that backward
      walking up an incline may place additional muscular demands on an
      individual.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535471
TI  - Rate of temperature increase in human muscle during 1 MHz and 3 MHz continuous
      ultrasound.
AB  - To achieve the thermal effects of ultrasound, the tissue temperature must be
      raised from 1 to > or = 4 degrees C, depending on the desired outcome of the
      treatment. In the past 25 years, there have been no in vivo studies that have
      measured rate of change in temperature during 1-MHz ultrasound treatments, and
      none have ever been performed with the 3-MHz frequency. Thus, we are left to pure
      speculation regarding how long to administer an ultrasound treatment. We
      performed this study to plot the rate of temperature increase during ultrasound
      treatments delivered at various intensities and frequencies. We inserted two 23
      gauge thermistors into each subjects' medial triceps surae at the following
      depths: 1 MHz at depths of 2.5 and 5.0 cm (12 subjects) and 3 MHz at depths of .8
      and 1.6 cm (12 subjects). Each subject received a total of four 10-minute
      treatments, one each at .5, 1.0, 1.5, and 2.0 W/cm2, and temperature was measured
      every 30 seconds. No significant difference was found in the rate of heating at
      the two depths (p = .987) within the same frequency and dose levels. The 3-MHz
      frequency heated significantly faster than the 1-MHz frequency at all doses
      tested (p < .001). On average, the rate of temperature increased per minute at
      the two depths of the 1-MHz frequency was: .04 degrees C at .5 W/cm2; .16 degrees
      C at 1.0 W/cm2; .33 degrees C at 1.5 W/cm2; and .38 degrees C at 2.0 W/cm2. The
      rate of temperature increase per minute at the two depths of the 3-MHz frequency
      was: .3 degrees C at .5 W/cm2; .58 degrees C at 1.0 W/cm2; .89 degrees C at 1.5
      W/cm2; and 1.4 degrees C at 2.0 W/cm2. The results of this research should enable
      clinicians to choose the correct frequency, intensity, and treatment time when
      using thermal ultrasound.

PMID- 8535472
TI  - Effect of running on volume of the foot and ankle.
AB  - Increases in volume of the lower extremities have been demonstrated in some
      exercises of short duration and varied intensities. The purpose of this study was
      to determine if running on a treadmill for 15 minutes increased volume of the
      foot and ankle when compared with walking. Twenty-one volunteers walked during
      one treatment session and ran during another session. Volumetric measurements
      were taken before and after each exercise. A change score was calculated for each
      subject for both sessions. A t test for related measures demonstrated a
      statistically significant difference (p < or = 0.05), with a larger volume
      occurring after running. Increases in volume most likely would not create
      problems in healthy individuals. Increases, however, may be harmful in
      individuals with circulatory disorders or with edema as a sequela of a foot or
      ankle injury.

PMID- 8535473
TI  - Rearfoot posture in subjects with patellofemoral pain.
AB  - The relationship between structural foot deformities and excessive subtalar joint
      pronation as being contributory to patellofemoral pain has not been well
      documented. It was the purpose of this study to assess the rearfoot posture in
      patients diagnosed with patellofemoral pain compared with a normal population. In
      addition, the intratester reliability in obtaining rearfoot measurements was
      assessed for right and left sides in 21 normal subjects. A goniometer was used to
      measure rearfoot posture in 30 female subjects (15 with patellofemoral pain and
      15 controls). Measurements were taken with the subjects prone and the subtalar
      joint in neutral. Intraclass correlation coefficients were good for both the
      right and left measurements (.87 and .86, respectively). A small but significant
      increase in rearfoot varus was found in the patellofemoral pain group compared
      with the control group (8.9 vs. 6.8 degrees; p = .0002). These results suggest
      that increased rearfoot varus may be a contributing factor in patellofemoral pain
      and should be assessed when evaluating the events at the subtalar joint and the
      lower extremity. In addition, it has been demonstrated that consistent rearfoot
      measurements can be obtained by an individual clinician.

PMID- 8535474
TI  - Reliability of the figure-of-eight method of ankle measurement.
AB  - Physical therapists need a reliable method by which to measure ankle girth
      following injury so that there can be clinical quantification of the volume of
      edema. The purpose of this study was to examine the intratester and intertester
      reliability of the ankle figure-of-eight method for the measurement of ankle
      size. Fifty healthy subjects were positioned on a plinth in a long sitting
      position. Four measurements were made by each of the three testers for a total of
      12 measurements per subject. The intraclass correlation coefficient was 0.99 for
      intertester reliability and 0.99 for intratester reliability. These results
      support the use of the ankle figure-of-eight method as a reliable tool for
      measuring ankle girth.

PMID- 8535475
TI  - Material properties: a factor in the selection and application of splinting
      materials for athletic wrist and hand injuries.
AB  - Athletic injuries to the wrist and hand are common in clinical practice. When
      indicated, the use of a protective playing splint enables athletes to continue
      sports participation. The purpose of this paper is to discuss the splinting
      material properties that determine the materials' suitability for use in
      fabrication of a protective playing splint. A second aim is to present currently
      available splinting materials. The clinical reasoning process for material
      application and selection is based on understanding material properties, the type
      and severity of the injury, phase of treatment, and type of sport. Of the
      materials included in this paper, only the low-temperature materials are
      acceptable for use in construction of rigid splints. The no heat or layered
      materials can be used for fabricating the semirigid splints. It is suggested that
      meaningful comparisons between the material properties can only be made if
      laboratory and clinical comparative studies are conducted to compare the physical
      and mechanical properties of the splinting materials used in athletic
      application.

PMID- 8535476
TI  - The 1st Meeting of The European Society for Impotence Research (ESIR). Halkidiki,
      Greece, 13-16 September 1995. Abstracts.

PMID- 8535477
TI  - Lest we forget.

PMID- 8535478
TI  - The current status of Dupuytren's disease.

PMID- 8535479
TI  - Manual muscle strength testing: intraobserver and interobserver reliabilities for
      the intrinsic muscles of the hand.
AB  - The reliability of manual muscle strength testing of the intrinsic muscles of the
      hand is reported. The muscle strengths of 28 patients who had neuropathies of the
      ulnar nerve or the ulnar and median nerves were graded by two physiotherapists to
      determine intraobserver and interobserver reliabilities. Muscle strength was
      graded using the numeric scale developed by the Medical Research Council (grades
      0 to 5). Reliabilities were established for nine muscles or muscle groups.
      Intraobserver reliabilities ranged from 0.71 to 0.96 and interobserver
      reliabilities from 0.72 to 0.93. It is difficult to isolate, and hence grade,
      most of the intrinsic muscles of the hand. Therefore, it is suggested that
      specific movements be tested and graded when assessing and evaluating muscle or
      nerve function.

PMID- 8535480
TI  - Manual muscle strength testing and dynamometry for bilateral ulnar neuropraxia in
      a surgeon.
AB  - This case study describes a patient who had bilateral neuropraxia of the ulnar
      nerve following a 5-day bicycle ride across the Swiss Alps. The patient, who was
      a surgeon, and the referring therapist were uncertain about the diagnosis at the
      time of referral. The purposes of this case study are to familiarize the hand
      therapist with "cyclist's palsy" and to illustrate how the recoveries of both
      nerves were followed using manual muscle strength testing and dynamometry. A form
      developed for the simultaneous assessment and comparison of the two measurements
      is presented. Muscle strength is tested and graded as suggested in another
      article of this issue.

PMID- 8535481
TI  - Early mobilization method for surgically repaired zone III extensor tendons.
AB  - A method for early mobilization of surgically repaired extensor tendons in zone
      III is outlined. Twenty-seven consecutive patients were treated between June 1985
      and January 1992 using this 6-week treatment method, which includes fabrication
      and application of a custom dynamic hand-based orthosis. The specific graded
      controlled motion regimen is described in detail. The central theme of this
      article is early controlled motion beginning within 4 days of surgical repair. A
      critical element to the successful outcome is the resting position, which is also
      outlined in detail.

PMID- 8535482
TI  - A pilot study of the reliability of the dynamic mode of one BTE Work Simulator.
AB  - This paper presents the results of a study of the reliability of the manual
      dynamic mode of one BTE Work Simulator. The study was part of an effort to
      develop a simple method of calibrating the BTE Work Simulator as an evaluation
      instrument. Weights attached to a 12-in nylon cylinder rotated the shaft of the
      exercise head against resistance generated by the Work Simulator. A timing device
      recorded drop times for one complete revolution of the nylon cylinder. The timing
      device consisted of a digital clock, a photo detector circuit, and a switching
      circuit. The photo detector recorded one revolution of the cylinder, and the
      switching circuit started and stopped the clock. Drop times were recorded as
      fixed weights attached to the nylon cylinder were allowed to drop. The test was
      repeated a number of times at each combination of weight and exercise level. A
      minimum of 40 tests were recorded with 4.96-, 10-, 15-, 25-, 30-, and 40-lb
      weights. This provided accurate measurement of the performance of the Work
      Simulator in the dynamic mode. Fluctuation in resistance caused drop times for
      any given weight to vary from -47% to +183.7% from the mean. In some cases the
      resistance fluctuation was sufficient to either prevent the weight from dropping
      or stop the weight before the cylinder had rotated one revolution. Resistance
      variation in the dynamic mode of the BTE Work Simulator was found to produce
      inconsistent performance. Testing that includes other Work Simulators is in
      progress.

PMID- 8535483
TI  - Early active mobilization for flexor tendons repaired using the double loop
      locking suture technique.
AB  - Current suture techniques limit the postoperative management for flexor tendons.
      A double loop locking suture (DOLLS) technique has been described that provides
      sufficient in vitro strength (average 4,400 g) for early active mobilization of
      the flexor tendon. This paper details four cases in which the flexor digitorum
      profundus (FDP) tendons were repaired using the DOLLS technique. Early active
      mobilization was initiated 3 to 7 days postoperatively. Results were classified
      according to Strickland's formula. Two patients achieved excellent results, one a
      good result, and one a fair result. One rupture of a flexor digitorum
      superficialis (FDS) tendon, which had been repaired with a modified Kessler
      technique, occurred. Although this FDS tendon ruptured, the FDP tendon, which had
      been repaired with the DOLLS technique, remained intact. With the use of a
      protective splint, early active mobilization of tendons repaired by the DOLLS
      technique appears to be an effective method for postoperative management.

PMID- 8535484
TI  - A literature search strategy using the broad topic of carpal tunnel
      syndrome/cumulative trauma disorders.
AB  - Searching the periodical literature for information relevant to a specific topic
      or diagnosis is an activity that must be undertaken by most therapists at one
      time or another. A literature search can be incomplete and performing it
      excessively time consuming unless a carefully planned search strategy is
      employed. This article presents the process and the results of a literature
      search of the broad topic of carpal tunnel syndrome/cumulative trauma disorders.
      The search involved both computerized and printed indexes.

PMID- 8535485
TI  - A method for converting a mallet finger splint into a boutonniere splint.

PMID- 8535486
TI  - Modification of the digital serial plaster casting technique.

PMID- 8535487
TI  - A modified dynamic traction splint for unstable intra-articular fractures of the
      proximal interphalangeal joint.

PMID- 8535488
TI  - Needs of occupational exposure sampling strategies for compliance and
      epidemiology.
AB  - Although a great deal of occupational exposure data is collected, it is probably
      insufficient to truly answer the question of legislative compliance, ill directed
      in terms of real workplace risks, and is of little subsequent use for
      epidemiological research. This paper is an attempt to summarise the more
      important components and requirements of a sampling strategy, and it is therefore
      aimed at those with this responsibility. Perhaps, all too frequently, the more
      esoteric nature of these issues and their research means that they are published
      in journals outside the normal sphere of readership, or when it is within that
      sphere the quantity of statistical nomenclature and content makes it too daunting
      to attempt to read. By simplifying and summarising, this paper is intended to
      help justify a change in the sampling programme and to initiate debate.

PMID- 8535489
TI  - Ventilation rate in office buildings and sick building syndrome.
AB  - OBJECTIVE: To examine the relation between ventilation rate and occurrence of
      symptoms of the eyes, nose, throat, and skin as well as general symptoms such as
      lethargy and headache, often termed the sick building syndrome. METHODS: A cross
      sectional population based study was carried out in 399 workers from 14
      mechanically ventilated office buildings without air recirculation or
      humidification, selected randomly from the Helsinki metropolitan area. The
      ventilation type and other characteristics of these buildings were recorded on a
      site visit and the ventilation in the rooms was assessed by measuring the airflow
      through the exhaust air outlets in the room. A questionnaire directed at workers
      inquired about the symptoms and perceived air quality and their possible personal
      and environmental determinants (response rate 81%). The outcomes were weekly work
      related symptoms experienced during the previous 12 months and symptom groups
      defined either by their anatomical location or hypothesised mechanism. RESULTS:
      In logistic regression analysis, the adjusted odds ratio (OR) for any symptom of
      interest was 3.03 (95% confidence interval (95% CI) 1.13 to 8.10) in the very low
      ventilation category of below 5 l/s per person and 2.24 (0.89 to 5.65) in the
      high ventilation category of over 25 l/s per person compared with the reference
      (15- < 25 l/s). The ORs for ocular (1.27, 1.11 to 1.46), nasal (1.17, 1.06 to
      1.29), skin symptoms (1.18, 1.05 to 1.32), and lethargy (1.09, 1.00 to 1.19)
      increased significantly by a unit decrease in ventilation from 25 to 0 l/s per
      person. CONCLUSION: The results suggest that outdoor air ventilation rates below
      the optimal (15 to 25 l/s per person) increase the risk of the symptoms of sick
      building syndrome with the sources of pollutants present in mechanically
      ventilated office buildings. The Finnish guideline value is 10 l/s per person.

PMID- 8535490
TI  - Seasonal changes in ambulatory blood pressure in employees under different indoor
      temperatures.
AB  - OBJECTIVE: The effect of indoor temperature control on summer and winter
      ambulatory blood pressure levels at work was studied. METHOD: Ambulatory systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) were monitored once in
      summer and once in winter in 101 healthy normotensive subjects aged 28-63 years,
      engaged in similar physical work, from two plants with and three without air
      conditioning. Subjects were interviewed about health related habits, and
      measurements of environmental and occupational conditions were obtained. RESULTS:
      After controlling for possible confounders, mean SBP and DBP during work were
      significantly higher in winter than in summer (delta SBP = 3.4 mm Hg, P = 0.035;
      delta DBP = 3.3 mm Hg, P < 0.003). The seasonal change in SBP and DBP showed an
      independent association with the presence or absence of air conditioning of the
      industrial plants (SBP: beta = 0.194, P < 0.0001; DBP: beta = 0.054, P = 0.038).
      The percentage of subjects with increases of more than 10 mm Hg from summer to
      winter was higher in plants without than with air conditioning. CONCLUSIONS: (1)
      In normotensive subjects ambulatory working BP varies by season, with higher
      values in winter. If validated for hypertensive subjects, it may be necessary to
      tailor drug treatment to these variations. (2) The findings make it clear that
      drawing valid conclusions from comparisons of BPs between groups requires
      controlling for several factors, particularly season of the year. (3) Climatic
      conditions in the industrial plant influence the magnitude of seasonal variations
      in BP. Work in plants without air conditioning places a considerable added load
      on the employee's cardiovascular system.

PMID- 8535491
TI  - Dose-response relation for vascular disorders induced by vibration in the fingers
      of forestry workers.
AB  - OBJECTIVES: To study the relation between the prevalence of vascular disorders
      (white finger) and vibration exposure in a group of 222 forestry workers, of whom
      164 (73.9%) had work experience limited to antivibration (AV) chain saws only and
      58 (26.1%) had operated both non-AV and AV chain saws. METHODS: The chain saw
      operators and 195 control workers never exposed to hand transmitted vibration
      were interviewed with health and workplace assessment questionnaires. The
      diagnosis of vibration induced white finger (VWF) was made on the basis of
      subjective symptoms of finger blanching and the results of a cold test with
      plethysmographic measurement of systolic blood pressure of the finger. Vibration
      was measured on a representative sample of AV and non-AV chain saws. Daily
      vibration exposure was assessed as eight hour energy equivalent frequency
      weighted acceleration (A(8)). A lifetime vibration dose was estimated for each of
      the forestry workers. RESULTS: The overall prevalence of VWF among the forestry
      workers was 23.4%. The diagnosis of VWF was made in 13.4% of the forestry workers
      who handled only AV chain saws and in 51.7% of those who had also operated non-AV
      chain saws in the past. Raynaud's phenomenon was found in 2.6% of the controls.
      In the forestry workers, the risk for VWF showed positive increments with each
      increment of vibration dose, suggesting a monotonic dose-response relation. The
      responsiveness to cold in the digital arteries of the forestry workers was also
      found to increase with increasing vibration dose and severity of VWF. The
      estimated relation between VWF and vibration exposure showed that the expected
      prevalence of VWF increased almost linearly to either A(8) (with exposure
      duration unchanged) or the number of years of exposure (with equivalent
      acceleration unchanged). CONCLUSIONS: In this study of VWF among forestry
      workers, the estimated dose-response relation showed that if the magnitude of
      vibration acceleration is doubled, the total duration of exposure should be
      halved to produce an equivalent effect. On the basis of the assessment of
      vibration exposure, the estimated risk for VWF in the study population was found
      to be lower than that predicted by the international standard ISO 5349. These
      findings suggest a revision of the risk estimates for VWF currently provided by
      ISO 5349.

PMID- 8535492
TI  - Acute effects of vibration from a chipping hammer and a grinder on the hand-arm
      system.
AB  - OBJECTIVES: The purpose of this study was to compare various effects on the hand
      arm system of vibration exposure from a chipping hammer and a grinder with the
      same frequency weighted acceleration. Grip and push forces were measured and
      monitored during the exposure. The various effects were: muscle activity
      (measured with surface electrodes), discomfort ratings for different parts of the
      hand-arm system (made during and after exposure), and vibration perception
      threshold (for 10 minutes before and 10 minutes after the exposure). RESULTS: No
      increase in muscle activity due to exposure to vibration was found in the hand
      muscle studied. In the forearm, conversely, there was an increase in both muscle
      studied. For the upper arm the muscle activity only increased when exposed to
      impact vibration. Subjective ratings in the hand and shift in vibration
      perception threshold were effected more by the grinder than the hammer exposure.
      CONCLUSION: These results show that the reaction of the hand-arm system to
      vibration varies with frequency quantitatively as well as qualitatively. They do
      not support the notion that one single frequency weighted curve would be valid
      for the different health effects of hand-arm vibration (vascular,
      musculoskeletal, neurological, and psychophysiological).

PMID- 8535493
TI  - Cancer in printing workers in Denmark.
AB  - OBJECTIVES: To study the cancer incidence in printing workers in Denmark.
      METHODS: The cohort of 15,534 men and 3593 women working in the printing industry
      in 1970 were followed up for death, emigrations, and incident cancer cases until
      the end of 1987. Their cancer incidence was compared with that of all
      economically active people in Denmark. The smoking and drinking habits reported
      by members of the printing trade unions at a survey in 1972 were compared with
      habits reported by members of other trade unions. RESULTS: Lung, bladder, renal
      pelvis, and primary liver cancers were in excess among the printing workers. The
      excess risks of lung cancer among the factory workers in newspaper and magazine
      production, of bladder cancer in typographers in printing establishments, of
      renal pelvis cancer in typographers and lithographers, and of primary liver
      cancer among lithographers and bookbinders exceeded those expected based on the
      reported smoking and drinking habits. CONCLUSION: Our results indicate, in line
      with a previous study from Manchester, that work with rotary letterpress printing
      was associated with an increased risk of lung cancer. The inconsistent results
      from studies on bladder cancer in printing workers may point to a risk confined
      to a certain subgroup. The sixfold risk of primary liver cancer in Danish
      lithographers warrants studies in other countries.

PMID- 8535494
TI  - Airway responsiveness and job selection: a study in coal miners and non-mining
      controls.
AB  - BACKGROUND: It has been suggested that health related job selection is a major
      cause of the healthy worker effect, and may result in inaccurate estimates of
      health risks of exposures in the working environment. Improved understanding of
      self selection, including the role of airway hyperresponsiveness, should improve
      accuracy in estimating occupational risks. METHODS: We evaluated symptoms of the
      respiratory tract, lung function, occupational and smoking histories, and airway
      responsiveness from a cross sectional survey of 478 underground bituminous coal
      miners and non-mining controls. Workers with abnormal spirometry were excluded
      from methacholine testing. RESULTS: Methacholine responsiveness (> or = 15%
      decline in forced expiratory volume in one second) was associated in both miners
      and controls with reduced ventilatory lung function and an increased risk of
      respiratory symptoms. Miners with the longest duration of work at the coal face
      had a low prevalence of methacholine responsiveness, compared with miners who had
      never worked at the coal face (12% v 39%, P < 0.01). Throughout their mining
      careers, miners who responded to methacholine were consistently less likely to
      have worked in dusty jobs than miners who did not respond to methacholine.
      CONCLUSIONS: These results provide evidence that workers who are employed in
      dusty jobs are less likely than their unexposed coworkers to show increased non
      specific airway responsiveness, presumably as a result of health related job
      selection. Surveys of workers in which responsiveness data are unavailable may
      underestimate the effects of dust exposure on respiratory health.

PMID- 8535495
TI  - Evaluation of biomarkers in plasma, blood, and urine samples from coke oven
      workers: significance of exposure to polycyclic aromatic hydrocarbons.
AB  - OBJECTIVE: The aim was to assess the significance of two biomarkers; antibody to
      benzo(a)pyrene DNA adducts and concentration of hydroxyethylvaline haemoglobin
      adducts in samples from a well studied group of coke oven workers. As a measure
      of exposure we have used 1-hydroxypyrene in urine. METHODS: Urine and blood
      samples were collected from coke oven workers and a control group. Samples from
      coke oven plant workers were collected in January and June. 1-Hydroxypyrene was
      measured in urine by high performance liquid chromatography (HPLC), antibodies to
      benzo(a)pyrene DNA adducts were measured by ELISA and hydroxyethylvaline
      haemoglobin adducts were measured by gas chromatography-mass spectrometry (GC
      MS). RESULTS: Mean urinary 1-hydroxypyrene in samples from coke oven workers
      varied from 1.11 to 5.53 umol/mol creatinine and 0.14 umol/mol creatinine in the
      control group. Workers at the top side had the highest values of urinary 1
      hydroxypyrene. Antibody to benzo(a)pyrene DNA adducts did not correlate with
      either 1-hydroxypyrene nor length of work at the coke oven plant. But antibody
      concentration in samples collected in January was predictive of the concentration
      in samples collected in June. A small non-significant increase in
      hydroxyethylvaline haemoglobin adducts was found in samples from coke oven
      workers relative to the control group when comparing smokers and nonsmokers
      separately. CONCLUSION: 1-Hydroxypyrene correlates well with exposure groups
      based on job description. Antibodies to benzo(a)-pyrene DNA adducts was related
      to people and not exposure. Work at a coke oven plant might lead to increased
      hydroxyethylvaline haemoglobin adducts.

PMID- 8535496
TI  - Monitoring of exposure to methylpentanes by diffusive sampling and urine analysis
      for alcoholic metabolites.
AB  - OBJECTIVES: To investigate the possibilities of personal ambient monitoring and
      biological monitoring for methylpentane isomers. METHODS: The performance of
      activated carbon cloth to absorb 2- and 3-methylpentane was studied by
      experimental vapour exposure followed by solvent extraction and gas
      chromatography (GC). Urine from workers and rats exposed to 2- and 3
      methylpentane was analysed by GC with or without acid or enzymatic hydrolysis.
      RESULTS: Carbon cloth absorbed 2- and 3-methylpentane linearly to exposures up to
      eight hours and to 400 ppm, and was sensitive enough to detect a 15 minute peak
      of exposure. The two isomers were clearly separated from hexane on a DB-1 column.
      For analysis of the urine, enzymatic hydrolysis was superior to acid hydrolysis.
      Exposure of rats to methylpentane vapours showed that 2-methyl-2-pentanol and 3
      methyl-2-pentanol were excreted in urine in proportion to the dose of 2
      methylpentane and 3-methylpentane, respectively. 2-Methyl derivatives of 1-, 3-,
      and 4-propanol, 2-methylpentane-2,4-diol, and 3-methyl-2-pentanol were minor
      metabolites. Analysis of urine from the exposed workers showed that 2-methyl- and
      3-methyl-2-pentanol are leading urinary metabolites after exposure to the
      corresponding methylpentane. CONCLUSIONS: Diffusive sampling is applicable to
      monitor 2- and 3-methylpentane vapours as is the case for hexane vapour. 2-Methyl
      2-pentanol and 3-methyl-2-pentanol will be markers of occupational exposure to 2
      methylpentane and 3-methylpentane, respectively. Also, 2-methylpentane-2,4-diol
      might be a marker of exposure to 2-methylpentane.

PMID- 8535497
TI  - Substantial decrease of blood lead in Swedish children, 1978-94, associated with
      petrol lead.
AB  - OBJECTIVES: To study the potential impact of environmental exposure to petrol
      lead, residential area, age, sex, and lead exposing hobby, on blood lead
      concentrations (BPb) in children. METHODS: In the south of Sweden, yearly from
      1978-94, BPb was measured in 1230 boys and 1211 girls, aged between 3 and 19
      (median 10; quartiles 9 and 12) years. RESULTS: For the samples of 1978, the
      geometric mean (GM) was 67 (range 30-250) micrograms/l in boys and 53 (18-161)
      micrograms/l in girls, whereas the corresponding GMs for 1994 were 27 (12-122)
      and 23 (12-97) micrograms/l. The sex difference was present only in children over
      eight. Moreover, residential area affected BPb; in particular, children living
      near a smelter area had raised BPbs. There was a clear ecological relation
      between BPb (adjusted GM) and annual lead quantity in petrol sold in Sweden,
      which was estimated to be 1637 tonnes in 1976 and 133 tonnes in 1993 (P < 0.001,
      ecological linear regression analysis, where a two year lag of petrol lead was
      applied). In the 171 boys and 165 girls who were sampled twice with an interval
      of one to four years, the decreases in BPb were estimated to be 6% (95%
      confidence interval 4%-8%) and 10% (8%-13%)/year, respectively. CONCLUSIONS: The
      present report points out the considerable beneficial effect of the gradual
      banning of petrol lead on the lead exposure affecting the population and
      differential sex specific BPb patterns due to a pronounced age effect in girls,
      which may be caused by older girls' lower food intake per kg of body weight,
      lower lung ventilation, cleaner life style, and loss of blood lead through
      menstrual bleedings.

PMID- 8535498
TI  - Enzymuria in a population living near a cadmium battery plant.
AB  - OBJECTIVES: To study the body burden of cadmium and signs of tubular dysfunction
      in a rural population living near a closed nickel cadmium battery plant. METHODS:
      Cadmium and N-acetyl-beta-glucosaminidase (NAG) in urine were measured in 72
      subjects who lived close to the plant. RESULTS: Residents living close to the
      plant had higher median urinary cadmium concentrations than those living farther
      away (1.01 v 0.46 nmol/mmol creatinine) and than a control group (0.2 nmol/mmol
      creatinine). There was a significant correlation between urinary cadmium and the
      excretion of NAG in urine as well as signs of tubular dysfunction in residents
      who excreted urinary cadmium above 0.5 nmol/mmol creatinine. CONCLUSION: Tubular
      dysfunction may appear in environmentally exposed subjects at lower cadmium body
      burdens than previously anticipated.

PMID- 8535499
TI  - Diabetes mellitus and arsenic exposure: a second look at case-control data from a
      Swedish copper smelter.
AB  - OBJECTIVES: To find out whether a newly found association between diabetes
      mellitus and arsenic in drinking water in Taiwan could be reproduced in copper
      smelters with arsenic exposure. METHODS: Extended analysis of a previous case
      control study from 1978 was based on death records and objective exposure
      information from the company. The final analysis included only those employed at
      the smelter. Cases were 12 people with diabetes mellitus on the death certificate
      and those for whom there was clinical information on this disease. Controls were
      31 people without cancer, cardiovascular and cerebrovascular disease as these
      disease categories had been associated with arsenic exposure in the original
      study and elsewhere. RESULTS: The odds ratios found for diabetes mellitus with
      increasing arsenic exposure categories were (reference level = 1), 2.0, 4.2, and
      7.0, but the 95% confidence intervals included unity. Unstratified test for trend
      was weakly significant, P = 0.03. CONCLUSIONS: Although based on small numbers,
      the findings provide some support for the suggestion that arsenic exposure could
      sometimes play a part in the development of diabetes mellitus.

PMID- 8535500
TI  - Differences in occupational mortality from pleural cancer, peritoneal cancer, and
      asbestosis.
AB  - OBJECTIVE: To assess whether the increased risk of disease related to asbestos in
      occupations from the construction and engineering industries applies equally to
      pleural cancer, peritoneal cancer, and asbestosis. METHODS: Analysis was based on
      deaths among men aged 20-74 in England and Wales during 1979-80 and 1982-90. (n =
      1,656,096). Information about cause of death and the last full time occupation of
      decedents was derived from death certificates. Proportional mortality ratios
      (PMRs) by occupation were calculated for each of pleural cancer, peritoneal
      cancer, and asbestosis. RESULTS: Altogether, 2848 deaths were attributed to
      cancer of the pleura, 362 to cancer of the peritoneum, and 281 to asbestosis.
      When occupations were ranked according to PMRs from these diseases, striking
      differences were found. The category of construction workers which included
      laggers had the highest mortality from peritoneal cancer (PMR 990, 64 deaths),
      but a PMR of only 160 (77 deaths) for pleural cancer. In contrast, several
      occupations with much higher mortality from pleural tumours had no excess of
      peritoneal cancer. PMRs for asbestosis related more closely to those for
      peritoneal than pleural cancer. CONCLUSIONS: These findings suggest that the
      exposure-response relations for diseases related to asbestos are not all linear,
      and that risks of pleural mesothelioma may be underestimated by simple
      extrapolation from observations in cohorts with heavy exposure.

PMID- 8535501
TI  - Further information on aluminium inhalation in silicosis.
AB  - OBJECTIVES: In previous studies, a significant reduction in biological activity
      of quartz by the surface chemistry of aluminium was noted. Aluminium lactate
      inhalation one month after quartz exposure significantly suppressed silicosis. In
      a recent study, it was noted that aluminium inhalation failed to alter the
      silicosis process after disease was recognised by standard chest radiography in
      the first year after monthly treatment. METHODS: That study was extended with the
      same groups of sheep, the aluminium treated group received weekly aerosol of 100
      mg of aluminium lactate for an additional two years. All sheep were evaluated at
      three-month intervals by chest radiography, lung function, and lung lavage.
      RESULTS: The sheep with silicosis had significantly reduced lung functions,
      increased cellularity, phospholipids, and hyaluronan. These changes persisted for
      several years without significant differences between the silicotic sheep with or
      without the aluminium aerosol treatment. CONCLUSION: Aluminium aerosol treatment
      of silicosis after radiographic recognition of disease and the end of exposure
      did not alter the disease process.

PMID- 8535502
TI  - Prevalence odds ratio v prevalence ratio--a response.

PMID- 8535503
TI  - Management of indoor air quality problems: "primum non nocere".

PMID- 8535504
TI  - Physical workload and gestational age at delivery.

PMID- 8535505
TI  - From morphogenes to morphogenesis.

PMID- 8535506
TI  - Ectopic expression of the Streptomyces coelicolor whiE genes for polyketide spore
      pigment synthesis and their interaction with the act genes for actinorhodin
      biosynthesis.
AB  - The whiE gene cluster of Streptomyces coelicolor is normally expressed shortly
      before sporulation in the aerial mycelium, leading to production of the grey
      polyketide spore pigment. By placing the whiE genes under the control of the
      thiostrepton-inducible tipA promoter, they were artificially expressed on
      plasmids or in the chromosome during vegetative growth in a strain deleted for
      the act genes, which control biosynthesis of the polyketide antibiotic
      actinorhodin. Certain combinations of whiE-ORFI-VII led to production of mycelial
      pigments; these were exported into the medium when whiE-ORFI was absent, but
      poorly in its presence. Combined with comparative sequence data, the results
      allowed deductions to be made, or confirmed, about the normal roles of the eight
      known genes, whiE-ORFI-VIII, as follows: whiE-ORFIII, IV, V encode the three
      components (ketosynthase, chain length factor and acyl carrier protein) of the
      whiE 'minimal' polyketide synthase (PKS) needed for assembly of the carbon chain
      of the spore pigment precursor; whiE-ORFII, VI, VII are likely to be involved in
      cyclizations of the nascent carbon chain; whiE-ORFVIII controls a late step in
      the spore pigment biosynthetic pathway, probably a hydroxylation; and whiE-ORFI
      may encode a protein needed for correct targeting or retention of spore pigment
      at an appropriate cellular location. In other experiments, genes encoding
      components of the act-PKS and whiE-PKS were artificially co-expressed. Each of
      the three whiE minimal PKS subunit genes could complement lesions in the
      corresponding act-PKS genes to produce actinorhodin or related mycelial pigments,
      and each of the three act minimal PKS genes could complement lesions in the whiE
      minimal PKS genes to cause spore pigmentation. Thus the two sets of PKS subunits,
      which are encoded by genes that have presumably diverged from a common ancestor,
      are still capable of biochemical 'cross-talk', but this is normally prevented
      because the gene sets are expressed in different 'tissues' of the differentiated
      Streptomyces colony. Ectopic expression of sets of whiE-PKS genes presumed to be
      sufficient to assemble a carbon chain caused inhibition of early growth of the
      strains, perhaps by causing interference with fatty acid biosynthesis; this
      yielded circumstantial evidence that the whiE-PKS gene products can also interact
      with those of the fatty acid synthase(s) of the organism.

PMID- 8535507
TI  - Amplification of 16S ribosomal RNA genes of autotrophic ammonia-oxidizing
      bacteria demonstrates the ubiquity of nitrosospiras in the environment.
AB  - Oligonucleotide sequences selected from the 16S rRNA genes of various species of
      ammonia-oxidizing bacteria were evaluated as specific PCR amplification primers
      and probes. The specificities of primer pairs for eubacterial, Nitrosospira and
      Nitrosomonas rRNA genes were established with sequence databases, and the primer
      pairs were used to amplify DNA from laboratory cultures and environmental
      samples. Eubacterial rRNA genes amplified from samples of soil and activated
      sludge hybridized with an oligonucleotide probe specific for Nitrosospira spp.,
      but not with a Nitrosomonas-specific probe. Lakewater and sediment samples were
      analysed using a nested PCR technique in which eubacterial rRNA genes were
      subjected to a secondary amplification with Nitrosomonas or Nitrosospira specific
      primers. Again, the presence of Nitrosospira DNA, but not Nitrosomonas DNA, was
      detected and this was confirmed by hybridization of the amplified DNA with an
      internal oligonucleotide probe. Enrichments of lakewater and sediment samples,
      incubated for two weeks in the presence of ammonium, produced nitrite and were
      found to contain DNA from both Nitrosospira and Nitrosomonas as determined by
      nested PCR amplification and probing of 16S rRNA genes. This demonstrates that
      Nitrosospira spp. are widespread in the environment. The implications of the
      detection of Nitrosomonas DNA only after enrichment culture are discussed.

PMID- 8535508
TI  - Rapid screening for bacterial phenotypes capable of biodegrading anionic
      surfactants: development and validation of a microtitre plate method.
AB  - The Biolog microtitre plate assay, which is based on tetrazolium dye reduction as
      an indicator of sole-carbon-source utilization, has been evaluated as a rapid
      method to investigate the biodegradation of five classes of anionic surfactant by
      pure and mixed cultures of bacteria. The assay gave reproducible results over a
      fourfold range of inoculum optical density, and the surfactant concentration was
      selected to provide a compromise between the length of the lag period prior to
      colour production and the maximum colour produced. A kinetic model was developed
      and used to analyse the appearance of colour in the assay and was found to give
      rise to three biologically significant parameters describing the processes
      underlying the assay. No false-positives were obtained with environmental
      isolates. The small number of false-negatives obtained (< 8% of the total) could
      be explained by the methodology used to prepare the bacterial inoculum. All
      isolates which were positive in the Biology assay were shown to be both primary
      and ultimate degraders of the test surfactant. These results show that the method
      provides a useful means of studying the biodegradation of anionic surfactants by
      both pure and mixed cultures of bacteria and will find use in the rapid analysis
      of biodegradation kinetics and specificities of larger numbers of individual
      isolates than hitherto possible. In addition, an important benefit of the
      methodology is that it can be used for direct analysis of the biodegradation
      potential of whole bacterial communities without having to make an artificial
      selection during laboratory growth.

PMID- 8535509
TI  - Informed strain improvement for lignin degradation by Phanerochaete
      chrysosporium.
AB  - The effect of breeding from the white rot fungus Phanerochaete chrysosporium
      ME446 on performance for lignin mineralization was examined. This model for
      informed strain improvement without mutagenesis is based on abundant restriction
      fragment length polymorphisms (RFLPs). Under optimized conditions for lignin
      mineralization, extracellular manganese peroxidase (MnP) but not lignin
      peroxidase (LiP) could be detected, so measurement of LiP activity is not a valid
      assay for lignin degradation. Mineralization of 14C-labelled synthetic lignin
      (14C-DHP) was used to compare the performance of the wild-type strain ME446 with
      those of sets of progeny strains. Meiotic progeny from strain ME446,
      heterokaryotic progeny of crosses between such strains, and meiotic progeny of
      one heterokaryotic strain were examined. In each case, a minority of strains
      performed more efficiently than the parental strain ME446. The greatest range of
      lignin-mineralization performance (70-fold) was found within the set of initial
      progeny of ME446 and the narrowest was within the set of secondary homokaryotic
      strains. This is consistent with the view that a moderate number of determinants
      contribute to lignin mineralization performance. However, performance did not
      correlate with the possession of any single allele of those for 38 previously
      defined RFLP markers. The results show that lignin mineralization performance can
      be improved by cycles of crosses and fruiting, without mutagenesis.

PMID- 8535510
TI  - The role of recognition in the induction of specific chitinases during
      mycoparasitism by Trichoderma harzianum.
AB  - The induction of chitinolytic enzymes in the biocontrol agent Trichoderma
      harzianum during parasitism on Sclerotium rolfsii and the role of fungal-fungal
      recognition in this process were studied. A change in the chitinolytic enzyme
      profile was detected during the interaction between the fungi, grown in dual
      culture on synthetic medium. Before coming into contact with each other, both
      fungi contained a protein with constitutive 1,4-beta-N-acetylglucosaminidase
      activity. As early as 12 h after contact, the chitinolytic activity in S. rolfsii
      disappeared, while that of T. harzianum (a protein with a molecular mass of 102
      kDa, CHIT 102) greatly increased. After 24 h of interaction, the activity of CHIT
      102 diminished concomitantly with the appearance of a 73 kDa 1,4-beta-N
      acetylglucosaminidase, which became clear and strong at 48 h. This phenomenon did
      not occur if the S. rolfsii mycelium was autoclaved prior to incubation with T.
      harzianum, suggesting its dependence on vital elements from the host.
      Cycloheximide inhibited this phenomenon, indicating that de novo synthesis of
      enzymes is taking place in Trichoderma during these stages of the parasitism. A
      biomimetic system based on the binding of a purified surface lectin from the host
      S. rolfsii to nylon fibres was used to dissect the effect of recognition. An
      increase in CHIT 102 activity was detected, suggesting that the induction of
      chitinolytic enzymes in Trichoderma is an early event which is elicited by the
      recognition signal (i.e. lectin-carbohydrate interactions). It is postulated that
      recognition is the first step in a cascade of antagonistic events which triggers
      the parasitic response in Trichoderma.

PMID- 8535511
TI  - The plant growth regulator methyl jasmonate inhibits aflatoxin production by
      Aspergillus flavus.
AB  - Aflatoxins are highly toxic and carcinogenic compounds produced by certain
      Aspergillus species on agricultural commodities. The presence of fatty acid
      hydroperoxides, which can form in plant material either preharvest under stress
      or postharvest under improper storage conditions, correlates with high levels of
      aflatoxin production. Effects on fungal growth and aflatoxin production are known
      for only a few of the numerous plant metabolites of fatty acid hydroperoxides.
      Jasmonic acid (JA), a plant growth regulator, is a metabolite of 13
      hydroperoxylinolenic acid, derived from alpha-linolenic acid. The volatile methyl
      ester of JA, methyl jasmonate (MeJA), is also a plant growth regulator. In this
      study we report the effect of MeJA on aflatoxin production and growth of
      Aspergillus flavus. MeJA at concentrations of 10(-3)-10(-8) M in the growth
      medium inhibited aflatoxin production, by as much as 96%. Exposure of cultures to
      MeJA vapour similarly inhibited aflatoxin production. The amount of aflatoxin
      produced depended on the timing of the exposure. MeJA treatment also delayed
      spore germination and inhibited the production of a mycelial pigment. These
      fungal responses resemble plant jasmonate responses.

PMID- 8535512
TI  - Chimeric FimH adhesin of type 1 fimbriae: a bacterial surface display system for
      heterologous sequences.
AB  - The FimH adhesin of type 1 fimbriae has been tested as a display system for
      heterologous protein segments on the surface of Escherichia coli. This was
      carried out by introduction of restriction site handles (BglII sites) in two
      different positions in the fimH gene, followed by in-frame insertion of
      heterologous DNA segments encoding two reporter sequences. In the selected
      positions such insertions did not significantly alter the function of the FimH
      protein with regard to surface location and adhesive ability. The system seemed
      to be quite flexible, since chimeric versions of the FimH adhesin containing as
      many as 56 foreign amino acids were transported to the bacterial surface as
      components of the fimbrial organelles. Furthermore, the foreign protein segments
      were recognized by insert-specific antibodies when expressed within chimeric
      proteins on the surface of the bacteria. The results from this feasibility study
      point to the possibility of using the FimH adhesin as a general surface display
      system for sizeable protein segments.

PMID- 8535513
TI  - Molecular analysis of the cso operon of enterotoxigenic Escherichia coli reveals
      that CsoA is the adhesin of CS1 fimbriae and that the accessory genes are
      interchangeable with those of the cfa operon.
AB  - A deletion mutation in csoA, the gene encoding the structural subunit protein of
      CS1 fimbriae of enterotoxigenic Escherichia coli of serotype O6:K15:H16 or H-,
      was constructed in the subcloned CS1 genetic determinant. The mutation resulted
      in the abolition of CS1 fimbrial adhesiveness. Complementation, in trans,
      involving the determinant with the csoA deletion mutation and the gene encoding
      the structural subunit protein, CsoA, expressed from compatible plasmids,
      restored the expression and adhesive ability of CS1 fimbriae. In addition, trans
      complementation was achieved between the cso determinant with the aforementioned
      deletion mutation and the cfaB gene encoding the structural subunit protein
      (CfaB) of CFA/I fimbriae, resulting in the expression of CFA/I fimbriae. The
      observation that heterologous assembly was possible between these two fimbrial
      systems, together with the knowledge that the adhesin of CFA/I fimbriae is the
      structural subunit, was exploited to investigate whether CsoA had adhering
      properties. A deletion mutation in cfaB was created in the CFA/I fimbrial
      determinant. Complementation of this mutation with csoA in trans resulted in
      expression of the CsoA antigen on the bacterial cell surface and restoration of
      bacterial adherence. As no minor subunits act as the adhesin in CFA/I fimbriae,
      adhesion was mediated by CsoA. Nucleotide sequencing of the DNA region downstream
      from csoA confirmed the absence of genes encoding minor subunits which might act
      as the adhesin. Two open reading frames were revealed which encoded proteins
      sharing considerable homology with proteins encoded by corresponding ORFs in the
      CFA/I fimbrial operon. These proteins underlie the functional similarities
      between the CS1 and CFA/I fimbrial systems, allowing heterologous expression of
      their respective subunits.

PMID- 8535514
TI  - Molecular cloning of a Coxiella burnetii gene encoding a macrophage infectivity
      potentiator (Mip) analogue.
AB  - The gene encoding a protein that reacted with antibodies specific for Legionella
      pneumophila macrophage infectivity potentiator (LpMip) was cloned from Coxiella
      burnetii, the obligate intracellular rickettsia that causes Q fever in humans.
      Nucleotide sequencing analysis revealed an ORF encoding a gene product of 230
      amino acids with a molecular mass of 25.5 kDa and a predicted pI of 10.7. The
      predicted amino acid sequence from the ORF shows similarity with Mip/Mip-like
      proteins of Legionella (46%) and Chlamydia (30%). Moreover, like LpMip, the amino
      acid sequence of the C terminus of this protein has over 35% identity to
      prokaryotic and eukaryotic FK506-binding proteins (FKBPs) that belong to a
      superfamily of immunophilins and are peptidyl-prolyl cis-trans isomerases
      (PPIases). When overproduced in Escherichia coli, the C. burnetii protein also
      exhibited PPIase activity. Taken together, these results demonstrate that C.
      burnetii encodes a Mip analogue (CbMip). A putative leader peptide at the N
      terminus of CbMip was detected by computer analysis. Furthermore, TnphoA
      mutagenesis demonstrated that in E. coli CbMip was secreted. In view of the role
      of Mip/Mip-like proteins in the pathogenesis of Legionella and Chlamydia, CbMip
      may be a C. burnetii virulence factor.

PMID- 8535516
TI  - The role of glutaminase in Rhizobium etli: studies with a new mutant.
AB  - In order to examine the role of glutaminase in Rhizobium etli, we isolated and
      characterized a R. etli glutaminase mutant (LM16). This mutant was selected for
      its impaired ability to grow on glutamine as nitrogen and carbon source while
      retaining the ability to grow on other nitrogen and carbon sources. The mutant
      showed very low levels of glutaminase activity under various growth conditions in
      comparison with the wild-type strain. With glutamine as the only nitrogen and
      carbon source, LM16 showed poor growth, with a very high content of glutamine,
      low glutamate content, and reduced ammonium excretion and 14CO2 evolution from [U
      14C]glutamine compared to the wild-type strain. This indicates that the main role
      of R. etli glutaminase is in the use of glutamine as carbon source. R. etli
      glutaminase also plays a role in maintaining the balance between glutamate and
      glutamine, as shown by the accumulation of glutamine and the low glutamate
      content of the mutant under different growth conditions. These results also
      indicate that glutaminase participates in a glutamine cycle in which it degrades
      glutamine which is then resynthesized by glutamine synthetase. The higher
      glutamine and lower glutamate content found in bacteroids of LM16 in comparison
      with bacteroids of the wild-type strain indicate that glutamine degradation by
      glutaminase plays an important role during the symbiosis between R. etli and
      Phaseolus vulgaris.

PMID- 8535515
TI  - A non-essential glutamyl aminopeptidase is required for optimal growth of
      Lactococcus lactis MG1363 in milk.
AB  - Degenerate PCR primers were designed from the N-terminal amino acid sequence of a
      glutamyl aminopeptidase (PepA) from Lactococcus lactis. These primers were used
      to screen a lambda library for clones containing the gene (pepA) encoding PepA.
      The DNA sequence of a 2.1 kb fragment containing pepA was determined. The
      sequence revealed the presence of one complete and two incomplete open reading
      frames (ORFs). The complete ORF encodes a putative protein of 353 amino acids
      with a predicted N-terminal sequence identical to that determined for purified
      PepA. The pepA gene was subcloned on an Escherichia coli plasmid vector and
      production of active PepA was confirmed by means of a zymogram. Mutants of L.
      lactis in which the pepA gene was inactivated grew to normal cell densities in
      milk but exhibited a reduced growth rate during the exponential phase. Thus
      whilst PepA is required for optimal growth it is not essential.

PMID- 8535517
TI  - Arylsulphatase from Alteromonas carrageenovora.
AB  - Arylsulphatase activity was identified in cultures of the marine bacterium
      Alteromonas carrageenovora, using methylumbelliferyl sulphate as substrate. In
      contrast with most other microbial arylsulphatases, arylsulphatase production in
      A. carrageenovora was not repressed by sulphate. The structural gene of
      arylsulphatase (atsA) was cloned and sequenced. An ORF of 984 bp was found,
      specifying a primary translation product of 328 amino acids with a molecular mass
      of 35797 Da. Arylsulphatase was partially purified from cell extracts of both A.
      carrageenovora and recombinant Escherichia coli. Both the recombinant and native
      enzymes exhibited a pI of 5.5, a Michaelis constant for methylumbelliferyl
      sulphate of 68 microM, and a molecular mass of approximately 35,000 Da in SDS
      PAGE analysis. Secondary structure comparisons using hydrophobic cluster analysis
      suggest functional analogies between the arylsulphatase of A. carrageenovora,
      that of Mycobacterium leprae and a 33.5 kDa protein from Porphyromonas
      gingivalis. It is speculated that these proteins are all glycosulphohydrolases,
      involved with desulphatation of sulphated polysaccharides.

PMID- 8535518
TI  - Membrane topology analysis of the Escherichia coli cytosine permease.
AB  - The Escherichia coli codBA operon encodes cytosine permease (CodB) and cytosine
      deaminase (CodA). CodB mediates uptake of exogenously supplied cytosine, and CodA
      catalyses the hydrolytic deamination of cytosine to uracil and ammonia. The
      hydropathic profile of CodB indicates that it is an integral cytoplasmic membrane
      protein possessing several transmembrane-spanning domains. The membrane topology
      of CodB was investigated by using gene fusions containing varying lengths of the
      amino-terminus of CodB fused to either alkaline phosphatase (AP) or beta
      galactosidase (BG). The AP activities expressed by the CodB-AP fusions are
      consistent with a topological model in which the amino- and the carboxy-termini
      of CodB are located in the cytoplasm, and in which CodB possesses 12 membrane
      spanning segments. The enzyme activities of most of the CodB-BG fusions support
      the model. However, the results obtained with some of the CodB-BG fusions
      illustrate the limitations of using BG as a reporter protein in studies of
      membrane protein topology.

PMID- 8535519
TI  - The dspA gene product of the cyanobacterium Synechocystis sp. strain PCC 6803
      influences sensitivity to chemically different growth inhibitors and has amino
      acid similarity to histidine protein kinases.
AB  - We have cloned and sequenced a gene of the cyanobacterium Synechocystis sp.
      strain PCC 6803 named dspA (encoding drug sensory protein A; DspA), mutations in
      which result in cross-resistance to the herbicides difunon and diuron, as well as
      to the calmodulin antagonists chlorpromazine and trifluoperazine. The dspA gene
      encodes a polypeptide of 663 amino acids with a predicted molecular mass of 74.5
      kDa. The molecular nature of two mutations in the dspA gene leading to the cross
      resistance has been determined. Targeted mutagenesis of the dspA gene was
      performed using a kanamycin-resistance gene cartridge. Resulting mutant strains
      were checked for resistance to difunon and chlorpromazine and showed cross
      resistance to both agents. The C-terminal portion of the deduced amino acid
      sequence of DspA shares significant similarity with the conserved region of
      histidine protein kinases (HPKs). Hydrophobicity analysis of the amino acid
      sequence of DspA indicated the existence of two hydrophobic regions in the N
      terminal portion that are characteristic of the bacterial sensory HPK family. We
      suggest that protein DspA is a HPK involved in chemical sensing.

PMID- 8535520
TI  - A ribonucleic antiterminator sequence (RAT) and a distant palindrome are both
      involved in sucrose induction of the Bacillus subtilis sacXY regulatory operon.
AB  - The Bacillus subtilis sacXY regulatory operon is involved in sucrose induction of
      the levansucrase sacB gene by an antitermination mechanism. In the presence of
      sucrose, the activated SacY antiterminator protein stabilizes the secondary
      structure of a ribonucleic antiterminator sequence (RAT) located in the leader
      region of the sacB transcript, and overlapping a rho-independent transcription
      terminator. Formation of the SacY-RAT complex prevents alternative formation of
      the terminator, allowing transcription of the downstream sequences. In the
      absence of sucrose, inhibition of SacY activity by SacX leads to termination of
      transcription. Expression of sacXY is also sucrose-inducible. This induction was
      previously shown to be mediated by SacY itself and/or SacT, another
      antiterminator involved in induction of genes belonging to a distinct sucrose
      pathway. These antiterminators are not activated at the same concentration of
      sucrose. We show here that sacXY induction occurs through activation of either
      SacY or SacT antiterminators, at their respective sucrose activation
      concentration. This result demonstrates a link between SacY- and SacT-mediated
      metabolic pathways. In addition, the sacXY leader region carries a RAT-like
      sequence, which however does not appear to overlap any apparent rho-independent
      transcription terminator. Site-directed mutagenesis experiments on this RAT-like
      sequence demonstrated its involvement in sucrose induction. Deletions generated
      in the sacXY leader region showed that a palindrome, located 100 nt downstream
      from the RAT-like sequence, also acts as a cis-acting element. Computer analysis
      of the leader RNA suggested that formation of the secondary structure of the RAT
      like sequence and the palindrome could be mutually exclusive.

PMID- 8535521
TI  - Insertional inactivation of the Streptococcus mutans dexA (dextranase) gene
      results in altered adherence and dextran catabolism.
AB  - Streptococcus mutans is able to synthesize extracellular glucans from sucrose
      which contribute to adherence of these bacteria. Extracellular dextranase can
      partially degrade the glucans, and may therefore affect virulence of S. mutans.
      In order to isolate mutants unable to produce dextranase, a DNA library was
      constructed by inserting random Sau3AI-digested fragments of chromosomal DNA from
      S. mutans into the BamHI site of the streptococcal integration vector pVA891,
      which is able to replicate in Escherichia coli but does not possess a
      streptococcal origin of replication. The resultant plasmids were introduced into
      S. mutans LT11, allowing insertional inactivation through homologous
      recombination. Two transformants were identified which did not possess dextranase
      activity. Integration of a single copy of the plasmid into the chromosome of
      these transformants was confirmed by Southern hybridization analysis. Chromosomal
      DNA fragments flanking the plasmid were recovered using a marker rescue
      technique, and sequenced. Comparison with known sequences using the BLASTX
      program showed 56% homology at the amino acid level between the sequenced gene
      fragment and dextranase from Streptococcus sobrinus, strongly suggesting that the
      S. mutans dextranase gene (dexA) had been inactivated. The colony morphology of
      the dextranase mutants when grown on Todd-Hewitt agar containing sucrose was
      altered compared to the parent strain, with an apparent build-up of extracellular
      polymer. The mutants were also more adherent to a smooth surface than LT11 but
      there was no apparent difference in sucrose-dependent cell-cell
      aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535522
TI  - Effects of cadmium and of YAP1 and CAD1/YAP2 genes on iron metabolism in the
      yeast Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae was more resistant to cadmium when the growth medium
      contained excess iron. Cadmium reduced the amount of iron taken up by cells
      during growth, and the cell ferrireductase activity was also strongly inhibited.
      These effects depended on the YAP1 and CAD1/YAP2 gene dosage. The growth rate of
      cells in iron-deficient conditions and their ferrireductase activity in the
      absence of added cadmium were also strongly affected by the dosage of YAP1 and
      CAD1/YAP2 genes. Our results suggest an indirect influence of these genes on iron
      metabolism, possibly via modification of the cell redox status.

PMID- 8535523
TI  - Aerotaxis in Halobacterium salinarium is methylation-dependent.
AB  - The behavioural response to a gradient of oxygen (aerotaxis) has been
      characterized in the archaeon, Halobacterium salinarium. When the gas surrounding
      a drop of H. salinarium strain S9-P culture was changed abruptly from 10% (v/v)
      O2 to 100% N2, the bacteria transiently increased the frequency of reversing
      before they adapted and resumed random swimming. When the gas was returned to 10%
      O2 the bacteria responded by swimming smoothly for approximately 45 s. Aerotaxis
      was strongest when respiration in H. salinarium was highest and when
      bacteriorhodopsin and halorhodopsin were not contributing to the proton motive
      force. Starvation for methionine of the auxotrophic H. salinarium essentially
      abolished the step-down aerotactic response. Methanol production from
      demethylation of methyl-accepting chemotaxis proteins was transiently increased
      in H. salinarium S9-P by a step down or step up in oxygen concentration, as
      observed in methylation-dependent chemotaxis in H. salinarium. The taxis-negative
      and methyltransferase-deficient mutant, H. salinarium strain Pho72 did not
      exhibit changes in methanol release in response to aerotaxis or chemotaxis
      stimuli. This is the first report of an aerotactic response that is dependent on
      methylation of methyl-accepting chemotaxis proteins. Aerotaxis in Escherichia
      coli and Salmonella typhimurium is independent of transducer methylation.

PMID- 8535524
TI  - Small cytoplasmic RNA (scRNA) gene from Clostridium perfringens can replace the
      gene for the Bacillus subtilis scRNA in both growth and sporulation.
AB  - Small cytoplasmic RNA (scRNA) is a member of an evolutionarily conserved signal
      recognition-particle-like RNA family. Using a DNA fragment of Bacillus subtilis
      scRNA gene as a probe, we cloned and characterized a Clostridium perfringens gene
      encoding the scRNA. Mapping the 5' and 3' ends of scRNA revealed that C.
      perfringens scRNA consists of 269 nucleotides: the sequence has about 70% primary
      sequence homology with B. subtilis scRNA. The predicted secondary structure
      appeared to be similar to that of B. subtilis scRNA, indicating that there are
      domains I and II in C. perfringens scRNA, in addition to domain IV. Functional
      analysis showed that C. perfringens scRNA could compensate for vegetative growth
      and allow the formation of heat-resistant spores in an scRNA-depleted B. subtilis
      strain, whereas Escherichia coli 4.5S RNA could not maintain sporulation. Since
      both E. coli 4.5S RNA and C. perfringens scRNA have the same binding specificity
      to B. subtilis Ffh protein, the difference in complementation activity reflects
      the function of domains I and II.

PMID- 8535525
TI  - Can phage defence maintain colicin plasmids in Escherichia coli?
AB  - We examined the role of plasmid-based phage defence in maintaining plasmids,
      using colicin plasmids in Escherichia coli as a model system. Experimental data
      indicated that the possession of a colicin plasmid can confer limited protection
      against bacteriophages. A continuous culture model, using these experimental
      values, indicated that the observed limited protection alone could selectively
      maintain colicin plasmids, without requiring a competitive advantage due to
      colicinogeny. Phage defence might explain the current maintenance of colicin
      plasmids, given the naturally occurring high levels of resistance to colicins.
      This model also suggests that many plasmids might be maintained in natural
      populations, in part, by phage resistance, including 'cryptic' plasmids for which
      no phenotype is known.

PMID- 8535526
TI  - Methanol oxidation mutants in Methylobacterium extorquens AM1: identification of
      new genetic complementation groups.
AB  - Two-hundred-and-eight new Methylobacterium extorquens AM1 methanol oxidation
      (Mox) mutants were isolated and placed into complementation groups.
      Complementation analyses identified new Mox groups in the Mxb and Mxc loci and at
      a new locus, Mxd. Thirty-seven mutants at the Mxb locus were divided into MxbM
      and MxbD complementation groups on the basis of their complementation pattern.
      Twenty-nine mutants at the Mxc locus fell into three complementation groups,
      MxcB, MxcQ and MxcE. The direction of transcription for genes at this locus could
      be inferred from the subclones. Eighteen of the new mutants were not complemented
      by previously isolated M. extorquens AM1 clones but were complemented by two new
      overlapping clones. This locus was called Mxd and the mutants fell into two
      complementation groups, MxdR and MxdS. Immunoblots from all these mutant classes
      showed that all of the Mxb and Mxc strains had substantially reduced levels of
      MxaF (large subunit of methanol dehydrogenase) and cytochrome cL, compared to the
      wild-type. These mutants, particularly the Mxb mutants, also had elevated levels
      of cytochrome c-553. These results are consistent with a role for the MxbMD and
      MxcBQE complementation groups in the regulation of expression of mxaF. The MxdR
      and MxdS mutants had normal levels of MxaF and both c-type cytochromes.

PMID- 8535527
TI  - The mxaAKL genes of Methylobacter albus BG8.
AB  - The facultative methanol utilizer Methylobacterium extorquens AM1 contains at
      least three genes (mxaA, K and L) that encode functions involved in providing
      calcium to the holoenzyme of methanol dehydrogenase, the enzyme that oxidizes
      methanol to formaldehyde in this strain. Methane-utilizing bacteria
      (methanotrophs) also contain methanol dehydrogenase, and evidence suggests that
      similar methanol oxidation (Mox) functions may be present in some of these
      strains. DNA fragments from Methylobacterium extorquens AM1 specific to mxaA,
      mxaK and mxaL were isolated for use as hybridization probes against genomic
      digests of a variety of methanotrophic bacteria. Only the mxaL probe showed
      substantial hybridization, and it was used to identify and isolate an 8.5 kb
      HindIII fragment from Methylobacter albus BG8 (a Type I methanotroph).
      Hybridization of restriction digests of this fragment to individual probes for
      Methylobacterium extorquens AM1 mxaA, K and L indicated that the relative mxa
      gene order in Methylobacter albus BG8 is A-K-L. A T7 dual promoter/polymerase
      protein expression system indicated that five polypeptides are expressed from a
      4.5 kb region of Methylobacter albus BG8 DNA in Escherichia coli, all transcribed
      in the same direction, and they apparently correspond to mxaACKDL. The functions
      of mxaC and mxaD are currently not known, but the order of mxaDL is reversed in
      Methylobacter albus BG8 compared to Methylobacterium extorquens AM1. When
      subclones of the Methylobacter albus BG8 fragment containing these genes were
      used as hybridization probes to genomic digests of methanotrophic bacteria,
      specific bands were detected that suggested a similar gene order in most cases.
      These data indicate that the mxaAKL region is relatively highly conserved in
      methanotrophs, and that in most cases the mxaAKL genes are grouped together in
      the same order as in the facultative methanol utilizer Methylobacterium
      extorquens AM1.

PMID- 8535528
TI  - Expression studies on four members of the pMGA multigene family in Mycoplasma
      gallisepticum S6.
AB  - A large family of related genes known as pMGA exists in the avian pathogen
      Mycoplasma gallisepticum but only a single member of this family was previously
      found to be expressed in one strain of this bacterium. In this work two unrelated
      strains of M. gallisepticum were also shown by amino-terminal sequencing to
      express a unique pMGA polypeptide in both cases. To investigate pMGA gene
      selection in M. gallisepticum, mRNA expression was analysed in M. gallisepticum
      strain 56 using reverse transcription-PCR (RT-PCR) and Northern blot techniques
      with probes for several members of the pMGA multigene family. It was shown that
      the pMGA message is 2.2 kb in size and is monocistronic. RT-PCR detected four
      different pMGA mRNA molecules but their relative yields were significantly
      affected by magnesium concentration. By quantitative Northern analysis, the
      relative abundances of the four pMGA mRNAs in M. gallisepticum S6 total RNA was
      determined: the pMGA1.1 mRNA predominated [1.88 ng (micrograms total RNA)-1] but
      at least three other pMGA genes were found to be transcribed but at much lower
      levels (20 to 40-fold lower). The pMGA1.1 mRNA is expressed at a level five times
      higher than the tuf gene, known to be one of the most abundantly expressed
      proteins in the prokaryotic cell. The start point of transcription for pMGA1.1
      was determined and probable promoter assigned. From these data it appears likely
      that transcriptional control plays a major role in the selection of pMGA gene
      expression in the M. gallisepticum cell.

PMID- 8535529
TI  - A witness to unconditional love.

PMID- 8535530
TI  - CAVHs for the critically ill.

PMID- 8535532
TI  - A breath of fresh air.

PMID- 8535531
TI  - Colors of the spectrum. Agency/registry nursing.

PMID- 8535533
TI  - Management perspectives. As a nurse manager in a home health service, I recently
      hired a nurse.

PMID- 8535534
TI  - November combines National Home Care and Hospice Months.

PMID- 8535535
TI  - Helen's heart. Interview by Janet Boivin.

PMID- 8535536
TI  - Cost-benefit aspects of treatment of hypertension in the elderly.
AB  - Treatment of elderly hypertensives with beta-receptor blockers and/or diuretics
      is cost-effective according to the analyses of the results of the Swedish Trial
      in Old Patients with Hypertension (STOP-Hypertension). The cost-effectiveness
      ratios are low and of the same magnitude for both men and women. The results with
      respect to reduced risk of cardiovascular disease in STOP Hypertension are also
      supported by several other studies using the same groups of drugs. The more
      modern drugs (calcium antagonists, alpha 1 blockers, and ACE inhibitors) have not
      proven their efficacy in the reduction of cardiovascular events in prospective
      studies of primary hypertension. It has, however, been shown that they lower
      blood pressure well also in the elderly and that they are cost-effective among
      the elderly if treatment with beta-receptor blockers and/or diuretics is
      contraindicated, provided that they lower the incidence of cardiovascular disease
      to the same extent as do beta-receptor blockers and diuretics. Studies tackling
      this latter question are under way, also in the elderly.

PMID- 8535537
TI  - Pharmacological backgrounds of the drug treatment of hypertension in the elderly.
AB  - A survey is given of the pharmacological backgrounds that are relevant for the
      drug treatment of essential hypertension in the elderly. Aging is accompanied by
      changes in the various autonomic receptors in the cardiovascular system, as well
      as in the endothelium of the large arteries. Vasodilator responses to drugs
      appear to be blunted in the elderly, although this effect is not necessarily
      caused by endothelial damage of the resistance vessels. Relevant pharmacokinetic
      changes associated with age are predominantly based on the continuous decrease in
      the renal clearance of drugs. Deficient compliance in elderly patients should be
      considered as a potential source of error in the drug treatment of elderly
      hypertensive patients. Large-scale evidence for the beneficial effect of
      antihypertensive drugs in the elderly with respect to morbidity and mortality is
      limited to diuretics and beta-blockers. The potential advantages and
      disadvantages of newer antihypertensives, such as ACE-inhibitors, calcium
      antagonists, alpha 1-adrenoceptor antagonists and urapidil are discussed on the
      basis of their pharmacological characteristics. Appropriate trials will be
      required to analyse the value of these drugs in the treatment of elderly
      hypertensives.

PMID- 8535538
TI  - Review of studies with urapidil in elderly hypertensives.
AB  - Urapidil, an antihypertensive agent with dual action (alpha 1-adrenergic
      antagonist and 5HT1A agonist) is well established in the treatment of arterial
      hypertension. The present brief review deals specifically with data obtained with
      urapidil in the treatment of elderly hypertensive patients. Some of these data,
      dealing with 245 patients aged > or = 65 years, have previously been published,
      but additional data from more than 5000 hypertensive patients in this age group
      on file will be reviewed as well. This unique and large data base clearly
      indicates that urapidil is an effective antihypertensive agent also when used in
      the treatment of elderly patients. Moreover, urapidil is well tolerated in this
      age group and has, in addition, a potentially favourable lipid profile. It may
      therefore be concluded that urapidil is well suited for the treatment of
      hypertension in the elderly.

PMID- 8535539
TI  - Blood pressure and serum lipids in hypertensive men and women aged 60-97 years.
AB  - OBJECTIVE: To report a large set of observations on blood pressure and blood
      lipids including high-density lipoprotein cholesterol in male and female
      hypertensive subjects aged 60 years or above. METHODS: Data on blood pressure
      (BP), total cholesterol (C), and high-density lipoprotein cholesterol (HDL-C)
      were made available on 5310 hypertensive subjects aged 60-97 years, from a
      European study on the effects of urapidil, a multifactorial antihypertensive
      agent (alpha 1-adrenoceptor antagonist+control 5HT1A-receptor stimulant).
      Observations before treatment were analysed to assess the male-female difference
      and the changes with age of BP and serum lipids. The subjects were divided into 7
      groups, aged 60-62, 63-65, 66-68, 69-71, 72-76, 77-79, and 80+, respectively, and
      a 2-factor ANOVA (sex and age groups) was used. RESULTS: Systolic BP increased
      with increasing age in both sexes (p < 0.0001). Over the whole age range, SBP was
      higher in women than in men (p < 0.0001). Diastolic BP remained unchanged in men
      and decreased with increasing age in women (p < 0.001). The C level was almost
      the same in men as in women, but tended to decrease with increasing age in women
      (p < 0.05). HDL-C was unchanged in men, but increased with increasing age in
      women (p < 0.006). In all age ranges, the HDL-C level was higher in women than in
      men (p < 0.0001). CONCLUSION: This study reports observations on BP and serum
      lipids in a large sample of hypertensives subjects aged 60-97 years. This type of
      data, especially on high-density lipoprotein cholesterol, is rare in the elderly.

PMID- 8535540
TI  - Arterial and cardiac changes in hypertension in the elderly.

PMID- 8535541
TI  - Addition of urapidil or metoprolol to the treatment of hypertensive non
      responders to nifedipine monotherapy: efficacy and metabolic effects. Italian
      Urapidil Study Group.
AB  - This study compared the effects on blood pressure and some metabolic variables of
      a 3-month period addition therapy of urapidil or metoprolol in 273 hypertensive
      non-responders to nifedipine sustained release (SR) monotherapy. This was a
      randomised, open-label, controlled, parallel-group comparative study, followed by
      another 3-month period during which all patients received the combination
      nifedipine SR-urapidil independently of the treatment they were previously
      randomized to. Both treatments caused significant falls in systolic (SBP) and
      diastolic blood pressure (DBP) when compared with the nifedipine SR monotherapy
      phase. The addition of urapidil to nifedipine SR caused a significant blood
      pressure reduction of 16.6/13.6 mmHg (p < 0.001), whereas after metoprolol the
      decrease was of 15.1/14 mmHg (p < 0.001). While in the overall population there
      was no statistically significant difference between the reduction caused by the
      two antihypertensive agents added to nifedipine SR, significant differences (DBP,
      p < 0.05; SBP, p < 0.01) were observed in the group of 51 patients aged at least
      60 years. Total cholesterol and LDL-cholesterol were significantly reduced (p <
      0.001) after the addition of urapidil to nifedipine SR, while, on the contrary,
      the addition of metoprolol to nifedipine SR was followed by a significant rise (p
      = 0.001). The changes caused by the two agents were statistically different among
      them (p < 0.01). The non-atherogenic HDL-cholesterol did not change during the
      addition of urapidil or metoprolol to nifedipine SR, while, the HDL/total
      cholesterol ratio was significantly increased after the addition of urapidil (p <
      0.01) and unmodified after the addition of metoprolol. Between-group analysis
      showed a significant difference (p = 0.005). Serum triglycerides did not change
      in the urapidil plus nifedipine SR group but significantly increased in the
      metoprolol plus nifedipine SR group (p < 0.001); between-group difference was not
      statistically significant. Plasma glucose was unchanged after the addition of
      urapidil whereas it was significantly (p < 0.001) increased in the metoprolol
      added group with a between-group difference statistically significant (p < 0.05).
      When metoprolol was substituted by urapidil during the second 3-month period, the
      negative effects on glucose, total cholesterol, LDL cholesterol and triglycerides
      were abolished while in the group already treated with urapidil plus nifedipine
      SR the favourable effects of urapidil plus nifedipine SR on total cholesterol,
      LDL-cholesterol and HDL/total cholesterol ratio were significantly increased
      compared with the end of the first 3-month treatment. The results of this study
      show that when urapidil and metoprolol are added to non-responders to nifedipine
      SR therapy there is a clinically and statistically relevant blood pressure
      reduction with both agents, with a therapeutic advantage for the combination
      urapidil + nifedipine SR in patients more than 60 years old. Moreover, the
      addition of urapidil was associated with a more favourable effect on serum lipids
      and glucose than that produced by the addition of metoprolol.

PMID- 8535542
TI  - Treatment of pulmonary hypertension in patients with chronic obstructive
      pulmonary disease: position of vasodilators with special focus on urapidil.
AB  - Pulmonary hypertension, generally defined by a resting pulmonary artery mean
      pressure higher than 20 mmHg, is a common complication of advanced chronic
      obstructive pulmonary disease (COPD). Pulmonary hypertension in COPD is of the
      "precapillary type" and is almost exclusively accounted for by the increased
      pulmonary vascular resistance (PVR). Among the factors leading to an increased
      PVR, acute as well as chronic alveolar hypoxia is by far the most important.
      Pulmonary hypertension is usually mild (between 20 and 35 mmHg) in COPD patients,
      but pulmonary artery pressure (PAP) may increase markedly and suddenly during
      exercise, sleep and episodes of acute respiratory failure. These acute increases
      of afterload can favour the development of right heart failure. Furthermore, even
      if the progression of pulmonary hypertension is rather slow (PAP increases by +
      0.5 mmHg/year as a mean), the level of PAP is a good indicator of prognosis in
      COPD patients. Consequently the treatment of pulmonary hypertension is justified
      in COPD. There are two treatments available so far, which are not mutually
      exclusive: vasodilators and long-term oxygen therapy (LTOT). LTOT may partly
      reverse hypoxic pulmonary vasoconstriction but is not always effective in
      reducing PAP in COPD. Patients with severe and persistent pulmonary hypertension
      despite oxygen and bronchodilator may be candidates for vasodilator therapy.
      Numerous vasodilators have been tested, but none has proved entirely
      satisfactory. Ideally the predominant vasodilator effect would occur in the
      pulmonary rather than in the systemic vascular bed, and systemic blood pressure
      should be maintained. The drug should not cause tachycardia and should be well
      tolerated. At the present time, inhaled nitric oxide (NO) is the only selective
      pulmonary vasodilator currently available, but NO inhalation is limited by
      toxicological consideration. Urapidil is known to be an alpha 1-adrenoceptor
      antagonist and an agonist of central 5HT1A-receptors, and should be considered as
      a vasodilator. Several studies have already demonstrated that this
      antihypertensive agent exerts favourable effects on pulmonary and cardiac
      haemodynamics when administered intravenously or orally to COPD patients with
      secondary pulmonary hypertension or cor pulmonale. Furthermore in patients with
      COPD or bronchial hyperreactivity no adverse effect is observed on ventilatory
      function, bronchial reactivity and gas exchange. Nevertheless, the potential
      benefit of this vasodilator needs to be confirmed in combination with LTOT by a
      pragmatic evaluation of its clinical efficacy and safety in COPD patients with
      secondary pulmonary hypertension.

PMID- 8535543
TI  - Hemorheology of arterial hypertension: influence of urapidil.
AB  - There is an increased prevalence of blood hyperviscosity in patients with
      arterial hypertension, and viscosity changes are related to hypertensive organ
      damage such as e.g. left ventricular hypertrophy. Various indices of hemorheology
      may be assessed in studies of hypertensive patients, most commonly viscosity,
      erythrocyte filtration, erythrocyte aggregation, platelet aggregation, etc. In
      vitro assessment of erythrocyte deformability and adrenaline induced platelet
      aggregation was performed after urapidil administration. Increasing
      concentrations of urapidil (25-150 microM) caused a dose dependent improvement of
      the erythrocyte rigidity index as well as inhibited adrenaline induced platelet
      aggregation. The beneficial effects of urapidil on hemorheology could add to its
      therapeutic effects in the treatment of arterial hypertension.

PMID- 8535544
TI  - Hypertension in the elderly: benefits of treatment.
AB  - It has long been known that hypertension increases the risk of cardiovascular
      morbidity and mortality and that this risk increases with age. It has taken much
      longer to establish that lowering the blood pressure in elderly subjects will
      reduce this risk. Early studies published in 1985-86 indicated that treating
      classical essential hypertension in elderly subjects who were mainly less than 75
      years of age, or even below 70 years, did reduce cardiovascular morbidity and
      mortality. More recent studies have extended the evidence and established that
      major benefits can be harvested by treating mild and moderate hypertension in
      subjects between 70 and 85 years who have classical hypertension with raised
      diastolic and systolic blood pressure. Recent evidence has also established that
      the treatment of isolated systolic hypertension in elderly patients up to the age
      of 80 and above, will reduce morbidity and mortality. In all of these recent
      studies, the major gain of lowering the pressure has been a reduction in the
      incidence of fatal and non-fatal stroke, but there is also some evidence of
      reduction in risk associated with coronary artery disease. Overall the evidence
      of benefit is sufficiently strong to advise the practising doctor to lower the
      blood pressure in elderly patients up to the age of 85 with raised diastolic or
      systolic blood pressure.

PMID- 8535545
TI  - Potential beneficial effects of urapidil in primary and secondary prevention of
      stroke.
AB  - Stroke is a partly preventable neurological disease associated with excessive
      economic cost. Adequate prevention of stroke and sufficient therapy in the acute
      phase will help to reduce the heavy burden of morbidity and severe economic
      impact. Hypertension as such, and even more so stroke itself, are known to
      influence cerebral autoregulation in a negative sense. With respect to the
      prevention of stroke, antihypertensive therapy should be accompanied by attempts
      to inhibit of atherogenesis, for instance via improvements of the lipid profile
      (lowering of LDL, elevation of HDL) or via inhibition of platelet aggregation. In
      conditions of acute stroke, a pharmacologically induced rise in intracranial
      pressure should be avoided, whereas cerebral perfusion pressure must be
      maintained. If possible, ischaemic tolerance should be increased. Also with
      respect to the secondary prevention of stroke, antihypertensive therapy should be
      aiming at maintaining cerebral blood flow, whereas the progression of
      atherosclerotic lesions should be impaired as much as possible. Urapidil may be
      characterised as a peripheral alpha 1-adrenoceptor blocker with additional
      sympathoinhibitory effect, triggered by the stimulation of central 5HT1A
      receptors. Urapidil, well documented as an effective antihypertensive agent in
      short- and long-term trials, also showed beneficial influence in the acute phase
      of stroke. After 3 years of treatment with urapidil (60 mg b.i.d.), the total
      cardiovascular risk proved reduced by 26%. In addition, urapidil influenced lipid
      profile, glucose metabolism, and platelet aggregation favourably in hypertensive
      patients. In animal experiments, urapidil improved the ischaemic tolerance of the
      brain. Taken together it would seem worthwhile to investigate urapidil as a
      possibly beneficial agent in the treatment of acute stroke, as well as in
      secondary prevention of this condition.

PMID- 8535546
TI  - Characteristics of an ideal antihypertensive therapy for elderly hypertensives.
AB  - Treatment of hypertension in the elderly has become not only accepted but also a
      highly ethical, effective and compelling procedure following the many clearly
      positive reports on the benefits of lowering elevated arterial pressure in
      elderly patients. So far most intervention studies in elderly hypertensive
      patients have used diuretics or beta-blockers or the two in combination as the
      moiety by which blood pressure has been lowered. However, from a theoretical
      point of view, more novel therapies could offer advantages that would translate
      into an even better reduction of cardiovascular morbidity and mortality than has
      been obtained with the traditional antihypertensive therapies used so far. Some
      of the studies in elderly hypertensives that are in progress using angiotensin
      converting enzyme inhibitors or calcium antagonists as the main therapies, e.g.
      the STOP-Hypertension-2 Study and the Syst-Eur Study, will be briefly reviewed
      here as will the large data base on urapidil, a dual action antihypertensive drug
      used in the treatment of elderly hypertensives. By careful evaluation of the
      effects of novel antihypertensive drugs, and the already existing data base on
      urapidil in elderly hypertensive patients, it is likely that still better
      reduction of risk can be obtained in the elderly hypertensives by the use of more
      novel therapies than diuretics and beta-blockers.

PMID- 8535547
TI  - Ambulatory blood pressure--defining normalcy of a very variable variable.

PMID- 8535548
TI  - Normotension and hypertension defined by 24-hour ambulatory blood pressure
      monitoring.

PMID- 8535549
TI  - Independent association between fasting plasma insulin and ambulatory blood
      pressure in 50-year-old women.
AB  - The aim of the present study was to investigate correlations between fasting
      insulin and ambulatory blood pressure in healthy 50-year-old women. Sixty-five
      women without anti-hypertensive medication were investigated at a Primary Health
      Care Centre in Enkoping, Sweden. Fasting plasma insulin, office blood pressure
      and heart rate were measured as well as ambulatory blood pressure and heart rate
      (Spacelab 90202). Log-transformed insulin correlated with all blood pressure
      recordings (r = 0.3-0.5; p < 0.05) but only with night-time heart rate (r = 0.3;
      p < 0.05). In multiple regression analyses log-insulin still correlated with
      night-time systolic blood pressure and heart rate, but not with the other blood
      pressure variables, after elimination of the influence of body mass index. We
      conclude that fasting plasma insulin shows an obesity-independent correlation
      with night-time systolic blood pressure and heart rate in healthy women, possible
      indicators of a "basic" sympathetic nervous outflow in muscle tissue during
      sleep.

PMID- 8535550
TI  - Insulin resistance and sympathetic nervous system activity in hypertensive and
      normotensive premenopausal women.
AB  - The aim of the present study was to compare insulin sensitivity and catecholamine
      responses to insulin in lean, hypertensive (HT) and normotensive (NT)
      premenopausal women. HT (BP 149 5/99 +/- 2 mmHg, n = 14) and NT (BP 128 +/- 4/81
      +/- 2 mmHg, n = 12) were matched for age (46 +/- 1 vs. 47 +/- 1 years) and body
      mass index. Insulin sensitivity was determined by fasting serum insulin, glucose
      disposal rate (GDR) and insulin sensitivity index (GDR/I) using euglycemic
      hyperinsulinemic glucose clamp technique. Sympathetic nervous system activity was
      assessed by plasma adrenaline and noradrenaline in arterialized venous blood at
      baseline and during euglycemic hyperinsulinemic glucose clamp. Insulin
      sensitivity index correlated negatively with total cholesterol in HT (r = -0.57,
      p < 0.05) and with body mass index (r = -0.42, p < 0.05, n = 26). The response in
      catecholamines to euglycemic hyperinsulinemia in HT differed from NT with an
      increase both in noradrenaline and adrenaline. Blood pressure and heart rate
      responses, however, did not differ between HT and NT. Fasting serum glucose did
      not differ between the two groups (4.7 +/- 0.1 mmol/l in HT vs. 4.9 +/- 0.1
      mmol/l in NT), nor did fasting serum insulin (16 2 mU/l vs. 13 mU/l). Glucose
      disposal rate (8.8 +/- 0.5 vs. 8.7 +/- 0.7 mg kg-1 body weight min-1) and insulin
      sensitivity index were similar (7.3 +/- 0.8 vs. 7.6 +/- 0.8 arbitrary units). We
      conclude that in lean, premenopausal hypertensive women insulin sensitivity is
      not reduced compared with age- and weight-matched normotensive women, but the
      hypertensives respond to hyperinsulinemia with increased plasma catecholamines,
      i.e. sympathetic nervous systemic activity. Also, insulin sensitivity correlates
      negatively with serum cholesterol. Thus, an insulin-hyperadrenergic interaction
      may possibly be involved as a pathogenetic factor in lean hypertensive women.

PMID- 8535551
TI  - Cholinergic receptor-mediated responses in the arteriolar and venous vascular
      beds of the human forearm.
AB  - In arterioles, acetylcholine (ACh) is a well known vasodilator. However, in veins
      a wide variation in responses to ACh has been reported. In the present study the
      effects of the cholinergic agonists acetylcholine and methacholine (MCh) were
      determined simultaneously both in arterial and venous vasculature in the forearm
      vascular bed of healthy volunteers by means of venous occlusion plethysmography.
      The vasodilator sodium nitroprusside (SNP) served as an endothelium-independent
      control agent. The vascular beds were preconstricted by the selective alpha 1
      adrenoceptor agonist methoxamine. Atropine, a non-selective muscarinic receptor
      antagonist, was used to antagonize the dilator effect of MCh. Overall we observed
      a weaker relaxant effect of ACh, MCh and SNP in the veins compared with their
      dilator responses in the arteries. ACh, which is highly sensitive to the
      hydrolytic inactivation by choline esterases, failed to induce a significant
      vasodilation in the venous vascular bed. Atropine blocked the dilator effects of
      MCh, indicating the involvement of muscarinic receptors. In arteries, MCh did not
      induce a significantly stronger vasodilatation than SNP on a molar basis.
      However, in veins, MCh had a weaker relaxant effect (p < 0.05).

PMID- 8535552
TI  - Effects of felodipine, metoprolol and their combination on blood pressure at rest
      and during exercise and on volume regulatory hormones in hypertensive patients.
AB  - The effects on blood pressure (BP) and heart rate (HR), at rest and during
      bicycle exercise, of the vascular selective calcium antagonist felodipine, the
      cardio-selective beta-blocker metoprolol, and of the two drugs in combination,
      were assessed in a double-blind, three-way cross-over study comprising 23
      patients with essential, mild to moderate hypertension. All three treatment
      regimens were given to each patient in randomised order for 4 weeks after a 4
      week placebo run-in period. Felodipine 10-20 mg daily, metoprolol 100-200 mg
      daily and the combination of felodipine 10-20 mg plus metoprolol 100 mg daily
      were all effective antihypertensive treatments both at rest and during exercise.
      The two drugs seemed to have additive effects and the effect on BP of the
      combination was greater than that of either drug given as monotherapy. The mean
      sitting BP was 148/103 mmHg at randomisation, after 4 weeks of placebo treatment,
      and 134/88, 134/94 and 121/84 mmHg, respectively, after 4 weeks' treatment with
      felodipine, metoprolol and the combination. Maximal exercise capacity was similar
      irrespective of treatment regimen, and the normal response to exercise BP and HR
      was maintained during all active treatments. Changes observed in volume
      regulatory hormones (PRA, aldosterone and ANP) were consistent with a direct
      tubular natriuretic-diuretic effect of felodipine and of beta-blocker attenuated
      release of renin. All treatment regimens were well tolerated and adverse events
      reported were usually mild and transient.

PMID- 8535553
TI  - Effect of indomethacin on blood pressure control during treatment with
      nitrendipine.
AB  - This study tested the hypothesis that treatment with a nonsteroidal anti
      inflammatory drug will not alter the hypotensive effect of a dihydropyridine
      calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years)
      had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy
      with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised
      crossover study in which the addition of indomethacin 25 mg three times daily was
      compared with placebo in treatment phases each of 4 weeks duration. Subjects were
      seen weekly and measurements in the last 2 weeks of each phase were compared.
      Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/-
      4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In
      6/15 (40%) of subjects the increase in supine diastolic blood pressure with
      indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin
      phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001).
      The study has demonstrated that concurrent treatment with the NSAID indomethacin
      impairs the blood pressure lowering effect of the dihydropyridine calcium channel
      antagonist nitrendipine. This increase in blood pressure with indomethacin in
      subjects treated with nitrendipine may represent either an independent pressor
      effect of indomethacin or a reduced vasodilator prostanoid contribution to the
      hypotensive effect of nitrendipine. This blood pressure increase may be
      sufficient to interfere significantly with clinical blood pressure control in
      some subjects.

PMID- 8535554
TI  - The Hypertension Optimal Treatment (HOT) Study: 12-month data on blood pressure
      and tolerability. With special reference to age and gender.
AB  - The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective,
      randomized, multicenter trial conducted in 26 countries. Its two main aims are to
      evaluate the relationship between three levels of target diastolic blood pressure
      (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular
      morbidity and mortality in hypertensive patients and the effects on morbidity and
      mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin)
      compared with placebo. Altogether 19,193 patients have been recruited and
      randomized and one-year data are now available for all patients. This is a report
      on the blood pressures achieved, the tolerability and other available data after
      12 months of follow-up of all patients. Special reference will be given to the
      subgroup of elderly patients (> or = 65 years, n = 6,113) as compared to younger
      patients (< 65 years, n = 13,080). On average, the target group < or = 90 mmHg in
      diastolic blood pressure has reached 86 mmHg, the target group < or = 85 mmHg has
      reached 83 mmHg and the target group < or = 80 mmHg has reached 81 mmHg. The
      percentage of patients that has obtained their target blood pressures is 84% in
      the target group < or = 90 mmHg, 72% in the target group < or = 85 mmHg and 57%
      in the target group < or = 80 mmHg at 12 months of follow-up. In the elderly
      subgroup (> or = 65 years of age) the percentage of patients at target is higher
      for all target groups, being 86, 76 and 61%, respectively, at 12 months.
      Antihypertensive treatment is initiated with a calcium antagonist, felodipine, at
      a dose of 5 mg once daily. If target blood pressure is not reached, additional
      antihypertensive therapy, with either an angiotensin converting enzyme (ACE)
      inhibitor or a beta-adrenoceptor blocking agent, is given. Further dose
      adjustments are made in accordance with a set protocol. As a fifth and final step
      a diuretic may be added. Side effects have been relatively few in this large
      multinational series of intensively treated hypertensive patients. Only ankle
      edema, 2.6% and 3.0%, and coughing, 1.3% and 0.8%, in young and elderly patients,
      respectively, exceed a frequency of 1%, and 88% of all patients are still taking
      their baseline therapy felodipine after one year. The one-year data presented
      here indicate that it should be possible to fulfill the primary aims of the HOT
      Study.

PMID- 8535555
TI  - The effect of aortic coarctation on expression of endothelin-1 and endothelin
      receptors in heart and lungs.
AB  - Expression of prepro-endothelin-1 (ppET-1), and endothelin (ET) receptor subtype
      (ETA, ETB) mRNAs was studied in atria, ventricles, and lungs of aortic coarctated
      rats. During 8 weeks following aortic banding, rats developed ventricular
      hypertrophy. The levels of expression of ppET-1, ETA- and ETB-receptors were
      significantly lower in the ventricles of coarctated rats than in sham-operated
      animals. In atria, the level of expression of ppET-1, ETA and ETB-receptors was
      not significantly changed. These results indicate that production of ET-1 is
      decreased and ETA and ETB-receptors are down-regulated in hypertrophied
      ventricles 8 weeks after aortic coarctation. This may be a compensatory response
      to pressure overload.

PMID- 8535556
TI  - Electrophysiologic characteristics of M cells in the canine left ventricular free
      wall.
AB  - INTRODUCTION: Recent studies have described the existence of M cells in the deep
      structures of the canine and human ventricle. The present study was designed to
      further characterize the M cell with respect to its distribution across the
      canine left ventricular free wall and the dependence of its action potential on
      [K+]o. METHODS AND RESULTS: We used standard microelectrode techniques to record
      transmembrane activity from deep subepicardial or transmural strips isolated from
      the canine left ventricular free wall near the base as well as subendocardial
      Purkinje fibers. M cells behavior (steep APD-rate relation) was observed at
      depths of 1 to 7 mm from the epicardial surface (deep subepicardium to mid
      myocardium). M cells were found to be distributed uniformly in the deep
      subepicardium and did not appear in discrete bundles. We observed transitional
      behavior throughout the wall. The maximum rate of rise of the action potential
      upstroke, Vmax, increased sharply between epicardium and deep subepicardium (176
      +/- 13 to 332 +/- 61 V/sec), remained high throughout the mid-myocardium and deep
      subendocardium, and returned to lower values only in the superficial layers of
      the endocardium (205 +/- 21 V/sec). The relationship between Vmax and takeoff
      potential in the M cell was fit by a Boltzmann equation with a V0.5 of -68.6 +/-
      1.5 mV and k of 3.4 +/- 0.5. The relationship between resting membrane potential
      (RMP) and [K+]o in the M cell was exponential from 8 to 20 mmol/L (58 mV change
      in RMP per 10-fold change in [K+]o), deviating from K+ electrode behavior at
      [K+]o < 8 mmol/L. RMP in M cells continued to hyperpolarize at [K+]o < 2.5
      mmol/L, reaching potentials of approximately -110 mV at [K+]o of 1 mmol/L. In
      contrast, subendocardial Purkinje fibers depolarized at these low levels of
      [K+]o. Unlike endocardium and epicardium, M cells developed early
      afterdepolarizations at low [K+]o and slow rates. CONCLUSIONS: Our data indicate
      that the M cells are widely distributed in the intramural layers of the canine
      left ventricular free wall. M cells and transitional cells occupy 30% to 40% of
      the left ventricular wall and an estimated 20% to 40% of the mass of the
      ventricles of the normal canine heart. They display characteristics common to
      both myocardial and specialized conducting cells. Like Purkinje fibers, M cells
      exhibit a relatively large Vmax and steep APD-rate relations that are modulated
      by [K+]o. Unlike Purkinje fibers, M cells do not appear in bundles, they do not
      depolarize at [K+]o < 2.5 mmol/L, nor do they exhibit phase 4 depolarization.

PMID- 8535557
TI  - Postshock sensing performance in transvenous defibrillation lead systems:
      analysis of detection and redetection of ventricular fibrillation.
AB  - INTRODUCTION: The sensing performance of transvenous lead systems may be
      adversely affected by the delivery of high-energy shocks. This may be due to the
      proximity of the sensing and energy-delivery electrodes on transvenous leads.
      METHODS AND RESULTS: The time required for detection of ventricular fibrillation
      and redetection after a failed first shock was compared in 93 patients with five
      different lead system-pulse generator combinations: Cadence--Endotak 60 series,
      Ventak P--Endotak 60 series, Jewel--Transvene, Cadence--TVL, and Cadence-
      Transvene. A total of 418 successful and 204 failed first shocks were delivered
      during induced ventricular fibrillation. Redetection times (RED) were
      consistently shorter than detection times (DET) in the Jewel-Transvene (RED minus
      DET: -1.9 +/- 0.8 sec, P < 0.0001), the Cadence-TVL (-1.6 +/- 1.0 sec, P <
      0.0001), and the Cadence-Transvene combinations (-2.0 +/- 0.9 sec, P < 0.0004).
      Redetection times were not significantly different than detection times in the
      Cadence-Endotak combination (0.9 +/- 3.1 sec; P = 0.09). Redetection times were
      significantly longer than detection times in the Ventak-Endotak combination (1.2
      +/- 2.3 sec; P = 0.034). Prolonged individual redetection episodes (> 8.2 sec)
      were observed in the Cadence-Endotak (7 [10%] of 73 episodes) and the Ventak
      Endotak (4 [10%] of 39 episodes), but not in the Jewel-Transvene, the Cadence
      TVL, and the Cadence-Transvene combinations. CONCLUSIONS: Redetection of
      ventricular fibrillation may be delayed in some transvenous lead-pulse generator
      combinations. Successful redetection of ventricular fibrillation following a
      failed first shock should be demonstrated prior to hospital discharge of patients
      with implantable defibrillators.

PMID- 8535558
TI  - Redetection revisited.

PMID- 8535559
TI  - Evidence for electrical organization during ventricular fibrillation in the human
      heart.
AB  - INTRODUCTION: Ventricular fibrillation is a most dangerous cardiac arrhythmia
      that has received considerable attention, yet its pattern of electrical
      activation remains controversial. The aim of this study was to investigate the
      degree of organization during the clinical arrhythmia and to examine the phase
      relationship between deflections in independent ECG leads. METHODS AND RESULTS:
      Ten recordings of ventricular fibrillation were examined. Each had been provoked
      during routine electrophysiological study. The mean duration of ventricular
      fibrillation was 21 seconds (range 11 to 34). Independent and approximately
      orthogonal ECG leads I, aVF, and V2 were recorded to computer at a sampling rate
      of 250 Hz. The phase relationship of each ECG lead pair was measured from the lag
      of peaks in their cross-correlation function (CCF). In 61% of the 1-second ECG
      epochs analyzed, CCF peak lag changed by < 20 msec compared to the previous
      epoch. Thus, the overall phase relationship was stable most of the time. Changes
      in CCF peak lag tended to be either gradual or to punctuate periods of stability.
      CONCLUSIONS: This study provides evidence of organized myocardial activation
      during human ventricular fibrillation.

PMID- 8535560
TI  - Histologic evolution of radiofrequency lesions in an old human myocardial infarct
      causing ventricular tachycardia.
AB  - INTRODUCTION: Radiofrequency (RF) ablation of ventricular tachycardia (VT) late
      after myocardial infarction may be difficult due to characteristics of the
      infarct containing the reentry circuit. RF lesions in these infarcts in humans
      have not been characterized. METHODS AND RESULTS: Catheter mapping and ablation
      of VT originating from an anterior wall infarct was performed 8 days and again 12
      hours prior to death. Pacing identified a region of abnormal conduction where RF
      ablation terminated VT. This region contained strips of myocytes sandwiched
      between endocardial fibrosis and dense scar. RF lesions ranged from 2 x 2 mm to 5
      x 10 mm and were up to 3 mm in depth. Acute lesions showed superficial thrombus
      and early coagulation necrosis without inflammation. Older lesions showed
      coagulation necrosis, sparse neutrophil infiltrate, minimal granulation tissue,
      hemorrhage, and mixed inflammatory infiltrate along the lumen without re
      endothelialization. CONCLUSION: In this patient, RF lesions had sufficient depth
      but not width to interrupt the thin, but potentially broad, sheets of myocytes in
      the reentry circuit. In thinned areas, RF lesions can extend to the epicardium.
      Selecting sites with abnormal electrograms confines RF lesions to the infarct
      region. Inflammation and hemorrhage could conceivably cause delayed effects of
      RF.

PMID- 8535561
TI  - Bradycardia-induced polymorphic ventricular tachycardia after atrioventricular
      junction ablation for sinus tachycardia-induced cardiomyopathy.
AB  - In a patient with severe left ventricular dysfunction resulting from chronic
      nonparoxysmal sinus tachycardia, rate control and improvement in left ventricular
      function were achieved with atrioventricular junction ablation and ventricular
      pacemaker implantation. Within 12 hours after the ablation procedure, several
      episodes of polymorphic ventricular tachycardia that may have been triggered by
      the abruptly decreased heart rate occurred. Recurrence of polymorphic ventricular
      tachycardia was prevented by an increase in pacing rate.

PMID- 8535562
TI  - Implantable atrial defibrillators.
AB  - Due to the limited efficacy of antiarrhythmic drugs for atrial fibrillation,
      several nonpharmacologic therapeutic options have evolved. One of these is an
      implantable atrial defibrillator. Recent studies have shown that internal atrial
      defibrillation is feasible with relatively low energies. To date, the optimal
      electrode configuration involves large surface area catheters in the right atrium
      and coronary sinus. In humans, atrial defibrillation can generally be achieved
      with < 2 J using this electrode configuration and a biphasic shock waveform. For
      shocks < 5 J, there is no significant pathological damage to the atria or
      coronary sinus. Further investigation is needed to guarantee that atrial
      defibrillation shocks do not provoke ventricular arrhythmias. Preliminary data
      suggest that atrial defibrillation shocks synchronized to R waves that are not
      closely coupled are safe. In addition, the shocks are well tolerated if the shock
      energy is < 1.5 J. With additional studies to confirm the safety of implantable
      atrial defibrillators, further reduce shock energy, and improve patient
      tolerance, an implantable atrial defibrillator can become an acceptable therapy
      for patients with symptomatic, paroxysmal atrial fibrillation.

PMID- 8535563
TI  - The automatic implantable defibrillator: it can be done, but should it?

PMID- 8535564
TI  - ACC/AHA Task Force Report. Guidelines for Clinical Intracardiac
      Electrophysiological and Catheter Ablation Procedures. A report of the American
      College of Cardiology/American Heart Association task force on practice
      guidelines (Committee on Clinical Intracardiac Electrophysiologic and Catheter
      Ablation Procedures). Developed in collaboration with the North American Society
      of Pacing and Electrophysiology.

PMID- 8535565
TI  - Use of murine models of cytokine-secreting tumor vaccines to study feasibility
      and toxicity issues critical to designing clinical trials.

PMID- 8535566
TI  - Survival and tissue distribution of human T-cell clones in SCID mice.

PMID- 8535567
TI  - Intrahepatic adoptive immunotherapy with autologous tumorcytotoxic macrophages in
      patients with cancer.

PMID- 8535568
TI  - Effect of local tumor irradiation and interleukin-2 therapy in different murine
      tumors.

PMID- 8535569
TI  - Unique characteristics associated with systemic adoptive immunotherapy of
      experimental intracerebral tumors.

PMID- 8535570
TI  - Reduction of therapeutic efficacy by a second cycle of PEG-IL-2.

PMID- 8535571
TI  - A phase II study of the continuous intravenous infusion of interleukin-6 for
      metastatic renal cell carcinoma.

PMID- 8535572
TI  - Comparison of 4- and 24-hour intravenous infusion schedules for granulocyte
      macrophage colony-stimulating factor.

PMID- 8535573
TI  - Isradipine, a calcium-channel antagonist, has immunosuppressor activity on T
      lymphocytes from peripheral blood and synovial fluid from patients with
      autoimmune arthritis.

PMID- 8535574
TI  - Who cares? Hospital, home or somewhere in between: the case for intermediate
      services.

PMID- 8535575
TI  - Complementary therapies in practice: the ethical issues.
AB  - This article explores some of the ethical issues associated with the use of
      complementary therapies in practice. The adopted terminology and related concepts
      are clarified. The term 'complementary therapy' is compared and contrasted with
      'alternative medicine' and 'non-conventional therapy'. The increasing emphasis on
      holistic nursing care is also discussed. Ethical issues of patient choice,
      informed consent and the principle of beneficence are examined in relation to
      complementary therapies. The article highlights the obligation of the nurse,
      midwife or health visitor to provide or facilitate holistic care including
      complementary therapies, such as massage or aromatherapy, for those clients who
      request such care, and where it can be demonstrated that there will be benefits
      for the patient. It is concluded that nurses should consider the possibility of
      incorporating or facilitating certain complementary therapies in their practice
      in order to benefit their patients. There is a corresponding need for an
      appropriate knowledge base, founded on nursing research, into the effectiveness
      and outcomes of complementary therapies. In addition, relevant educational
      courses should be developed.

PMID- 8535576
TI  - Advanced clinical roles: investigating dilemmas and changing practice through
      action research.
AB  - A new career structure for clinical nurses was implemented in 1987 in Victoria
      with the intention of providing clinical advancement and material rewards for
      nurses in clinical settings. This paper explains how participatory action
      research was used to explore some of the issues inherent in the role of the
      associate charge nurse. The clinical/management tension and the role expectations
      formed within the taken-for-granted rituals and routines of the ward and the
      hospital managerial structure are examined.

PMID- 8535577
TI  - The gentle touch.
AB  - This research study, which, because of its small numbers should be regarded as
      more of a pilot study, investigated the effect that therapeutic touch may have on
      measurable physical signs of the subjects involved. It also looked at any change
      this complementary therapy may have made in health perception immediately
      following the experiment and 1 week later. The design is modelled on that of
      Quinn (1984), eminent researcher in the field of energy exchange. Therapeutic
      touch is a misnomer because physical touch is not necessary--it is the energy
      field that is touched.

PMID- 8535578
TI  - Stress among student nurses: is it practical or academic?
AB  - Previous research into stress among student nurses has only concentrated on the
      practical aspects of nursing and has ignored stress caused by the academic side
      of training. In comparing Registered General Nurse (RGN) and Diploma of Higher
      Education in Nursing (Dip. HE Nursing) students using a modified nurses stress
      scale, the intensity of stress was investigated. It was hypothesized that there
      would be a difference in the total stress scores between the two pre-registration
      education courses as well as within the practical and academic elements. Dip. HE
      Nursing students were significantly more stressed than RGN students, but equally
      for practical and academic elements. RGN students were significantly more
      stressed on the practical elements. Factors analysis clearly identified two
      factors: (i) the practical elements, and (ii) the academic elements of nursing. A
      third factor was also identified and this was related to stress induced by issues
      concerning death and suffering in the patient. These results have implications
      for the development of the nurse education course (Dip. HE Nursing) which is
      still in its infancy.

PMID- 8535579
TI  - The nutritional management of acute renal failure.
AB  - Acute renal failure (ARF) is a syndrome in which the kidneys are unable to
      excrete the products of metabolism. The failure of renal function is rapid in its
      onset but potentially reversible. It occurs rapidly, within 8 weeks of renal
      injury resulting in a rapid increase in serum urea and creatinine concentrations
      in patients with previously normal renal function. It is a condition
      traditionally associated with a high mortality rate, often due to the
      complications of sepsis, delayed wound healing and disrupted haemocoagulation.
      Survivability has been demonstrated to be improved by early appropriate
      nutritional support (Bartlett et al., 1986) although in practice this is often
      difficult to achieve as nutritional support is complex. In the past high
      morbidity and mortality rates were related to infections and inadequate
      nutritional intake. This resulted from unnecessary protein restrictions in an
      attempt to control uraemic symptoms (Thomas, 1988). To a large extent
      survivability of ARF has still not been greatly improved even with modern
      antibiotics and the careful dietary assessment of ARF patients. This reflects the
      complexity of managing patients with this condition. However, appropriate dietary
      management of ARF patients is essential to improve their long-term prognosis.
      Although the precise form this takes remains a contentious issue amongst
      clinicians.

PMID- 8535580
TI  - Assessing patient satisfaction. Part 1. The research process.
AB  - The research reported in this article formed part of a project evaluating nursing
      developments in four demonstration wards in one health authority, and the article
      focuses on evaluation of patient satisfaction. The evaluation of patient
      satisfaction is a topic surrounded by much methodological debate and therefore it
      was necessary to clarify the issues involved at the planning stage of the study.
      The 'process' aspects of evaluating patient satisfaction will be discussed here,
      while the content of patient interviews will be the subject of Part 2.

PMID- 8535581
TI  - Nurse involvement in cardiac rehabilitation prior to hospital discharge.
AB  - Interviews were undertaken with 202 men admitted to five hospitals in northeast
      England following an uncomplicated first myocardial infarction. The likelihood of
      patients speaking to a nurse about recovery or seeing a physiotherapist,
      dietician or specialist rehabilitation nurse, varied considerably between
      hospitals. Whilst virtually all patients received written information concerning
      some aspect of life-style change or cardiac rehabilitation, the quality and range
      of information, particularly with regard to information about stress or anxiety,
      was frequently limited. Instructions about seeing a general practitioner
      following discharge were often vague; formal rehabilitation programmes, where
      they existed, excluded some patients. The study suggests that much patient
      education is dependent on the provision of written information alone, and that
      further evaluation of the effectiveness of self-help material supported by
      nursing input is desirable.

PMID- 8535582
TI  - Spiritual care of chronically ill patients.

PMID- 8535583
TI  - Psychological care of the ventilated patient.

PMID- 8535584
TI  - Wither the consultant or the specialist revisited.

PMID- 8535585
TI  - Streamlining CME administration.

PMID- 8535586
TI  - The ethical uses of human tissue.

PMID- 8535587
TI  - The outcome of Helicobacter pylori infection.
AB  - Duodenal ulcer disease correlates strongly with Helicobacter pylori infection.
      Ulceration is not, however, a common result of H. pylori infection. Whether this
      is due to differences in the hosts or the strains of H. pylori remains at issue.

PMID- 8535588
TI  - Hepatic cryotherapy for metastatic liver tumours.
AB  - Liver resection is the treatment of choice for resectable hepatic metastases;
      however, most patients have unresectable disease when diagnosed. Hepatic
      cryotherapy has been advocated to treat unresectable tumours in the liver
      although its precise role is still being evaluated. This article discusses
      mechanisms of action, technical considerations, current indications and the early
      results of cryotherapy in treating metastatic liver disease.

PMID- 8535589
TI  - Organisation of blood transfusion services.
AB  - Worldwide, the availability of blood product support for patients varies
      considerably, not only in quantity and in standards but also with regard to
      safety from infections, and specifications for components. Similarly, the
      organisation responsible for providing blood varies from one country to another.
      This article discusses the organisation of transfusion services in the UK,
      describing how the blood supply is provided and looks briefly at the structure of
      the organisations involved.

PMID- 8535590
TI  - Fetal malformations diagnosed antenatally 1: General principles.
AB  - Fetal malformations can be diagnosed antenatally by biochemical screening,
      karyotype analysis or ultrasound scanning. Good teamwork and communication is
      necessary between obstetrician, paediatrician, geneticist and ultrasonographer to
      explain the significance of any abnormality to a pregnant woman.

PMID- 8535591
TI  - Decision-making in surgery: how should an inguinal hernia be repaired?
AB  - The objective in inguinal hernia surgery is to provide a tension free repair
      wherever there is a posterior inguinal canal weakness. Mesh repair is at present
      undergoing a resurgence in popularity as the method of choice, inserted either at
      open surgery or laparoscopically.

PMID- 8535592
TI  - Treatment of priapism during transurethral resection of the prostate.

PMID- 8535593
TI  - Cutaneous manifestations of non-HIV immunosuppression.
AB  - Advances in organ transplantation and chemotherapeutic techniques have led to an
      increased interest in both the early and long-term complications of
      immunosuppression. This article reviews many of the cutaneous complications and
      highlights the importance of regular skin surveillance in these patients.

PMID- 8535594
TI  - Non-radiological investigation of pancreatic disease.
AB  - Pancreatic exocrine insufficiency is investigated by long established techniques:
      either by duodenal intubation studies, or by indirect functional methods. Serum
      markers and specific gastrointestinal hormones are available for the diagnosis of
      pancreatic inflammation, carcinoma, and rare pancreatic endocrine tumours. The
      clinical utility of these diagnostic tests is discussed in this article.

PMID- 8535595
TI  - Anaesthesia for cerebral aneurysm surgery.
AB  - Care of patients with subarachnoid haemorrhage caused by ruptured cerebral artery
      aneurysm requires careful assessment of neurological function and prevention of
      rebleeding and ischaemia throughout the perioperative period. An understanding of
      the cerebral protection techniques used during periods of ischaemia or
      circulatory arrest will assist the provision of optimal conditions for successful
      surgical treatment of the aneurysm.

PMID- 8535596
TI  - Radiological treatment of acute oesophageal food impaction.

PMID- 8535597
TI  - General management in the NHS.
AB  - The implementation of general management was a bold and innovative development.
      This article considers the emergence of the general management function and its
      impact upon medicine then and now.

PMID- 8535598
TI  - Anaesthesia with failed intubations.

PMID- 8535599
TI  - Anaesthesia with failed intubations.

PMID- 8535600
TI  - Procedures of lumbar puncture in paediatrics.

PMID- 8535601
TI  - Stridor in the small infant.

PMID- 8535602
TI  - Another look at collagen V and XI molecules.
AB  - The fibrillar collagens are the most abundant proteins of extracellular matrices.
      Among them, collagens V and XI are quantitatively minor components which
      participate in the formation of the fibrillar collagen network. Since these
      collagens were discovered, studies have demonstrated that they may play a
      fundamental role in the control of fibrillogenesis, probably by forming a core
      within the fibrils. Another characteristic of these collagens is the partial
      retention of their N-propeptide extensions in tissue forms, an unusual
      observation in comparison to the other known fibrillar collagens. The tissue
      locations of collagens V and XI are different, but their structural and
      biological properties seem to be closely related. It has been shown that their
      primary structures are highly conserved at both the gene and protein levels, and
      that these conserved features are the bases of their similar biological
      properties. In particular, they are both resistant to mammalian collagenases, and
      surprisingly sensitive to trypsin treatment. Collagens V and XI are usually
      buried within the major collagen fibrils, although they have both cell adhesion
      and heparin binding sites which could be of crucial importance in physiological
      processes such as development and wound healing. It has became evident that
      several molecules are in fact heterotypic associations of chains from both
      collagens V and XI, demonstrating that these two collagens are not distinct types
      but a single type which can be called collagen V/XI.

PMID- 8535603
TI  - Degradation of hamster amelogenins during secretory stage enamel formation in
      organ culture.
AB  - Increasing amelogenin heterogeneity during pre-eruptive enamel formation has been
      explained by proteolytic cleavage of a parent amelogenin, differences in
      posttranslational modifications, translation of multiple alternative spliced mRNA
      transcripts or combinations of these possibilities. We investigated the
      possibility of proteolytic degradation of amelogenins during secretory
      amelogenesis by pulse-labelling amelogenins with [3H]proline followed by a pulse
      chase, all under organ culture conditions. The results indicate that during pulse
      chase, hamster molar tooth explants rapidly released substantial amounts of the
      radioactivity into the culture medium, as non-trichloroacetic-acid precipitable,
      noncollagenous 3H-activity at the expense of radioactivity associated with the
      proteins in the enamel space. Simultaneously, there was a continuous
      mineralization of the forming enamel in vitro as shown by an increase in total
      calcium content of the explants. Western blotting, microdissection studies and
      fluorography of radiolabelled matrix proteins after SDS-PAGE indicated that after
      an 8-h labelling, three radioactive amelogenin species could be extracted from
      forming enamel, one prominent species of molecular mass 26 kDa and two less
      prominent ones of 28 and 22 kDa. During pulse chase more amelogenin bands with
      lower molecular mass became apparent, a pattern similar to that observed in vivo.
      Examination of amelogenin blots with the glycan assay showed that none of the
      hamster amelogenins stained for carbohydrate. We conclude that changes in the
      amelogenin profiles during enamel development of cultured hamster explants are
      similar to those observed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535604
TI  - Three-dimensional analysis of mineralizing turkey leg tendon: matrix vesicle
      collagen relationships.
AB  - The spatial and temporal relationships of mineral deposition between matrix
      vesicles and type I collagen fibrils have been studied in the turkey leg tendon
      by electron microscopy of cross sections and serial longitudinal thin sections
      and by electron tomography of longitudinal thick sections. Serial sectioning and
      electron tomography allow three-dimensional analysis of spatial relationships,
      overcoming the problems of missing depth information and over-projection of
      adjacent structures which exist for two-dimensional projections of isolated
      sections. These techniques reveal that while mineral deposits within matrix
      vesicles are found remote from calcifying collagen fibrils, the reverse
      relationship does not occur; all collagen-associated mineral can ultimately be
      linked to mineral-laden vesicles. These results suggest a temporal sequence of
      calcification beginning in matrix vesicles and spreading to adjacent collagen
      fibrils.

PMID- 8535605
TI  - Osteopontin is a constitutive component of normal elastic fibers in human skin
      and aorta.
AB  - Osteopontin is an acidic matrix protein, mainly expressed in mineralized tissues,
      kidney and atherosclerotic vessels; its biological role is still largely
      undefined. In the present study, immunocytochemical approaches showed that
      osteopontin is localized within normal elastic fibers of human skin and aorta.
      Antibodies raised against human bone osteopontin (LF7) or against human
      osteopontin synthetic peptide (amino acids 1-10, LF19) recognized epitopes
      associated with the amorphous material within the elastic fibers. Elastic fiber
      associated microfibrils were always negative. The positivity for osteopontin of
      the elastic fibers was independent of age and could be observed in fetal skin and
      aorta as well as in the same of children, young adults and old subjects. The
      altered elastic fibers in the skin of old individuals were only fairly positive
      for osteopontin. The presence of osteopontin within the elastic fibers suggests
      that it may play a role against the observed tendency of elastic fibers to favor
      mineral precipitation. A role of osteopontin in modulating crystal nucleation and
      growth in mineralizing tissues and, more generally, in conditions in which
      mineral precipitation should be controlled is also possible.

PMID- 8535606
TI  - Mesenchymal cell chondrogenesis is stimulated by basement membrane matrix and
      inhibited by age-associated factors.
AB  - During development of the embryonic limb, differentiation of mesenchymal
      progenitor cells into chondrocytes is regulated by cell shape, extracellular
      matrix, and growth and differentiation factors. In this study, reconstituted
      basement membrane (Matrigel) prepared from mouse Englebreth-Holm-Swarm tumor
      tissue was found to stimulate mesenchymal cell chondrogenesis in vitro and the
      production of cartilage at ectopic sites in athymic mice. The rate of
      chondrogenesis of mesenchymal cells from chick limb bud was increased four-fold
      by the addition of 400 micrograms/ml Matrigel to the media of micromass cultures,
      and this activity was not blocked by neutralizing antibodies to transforming
      growth factor-beta (TGF-beta) or fibroblast growth factor (FGF). Mesenchymal
      cells cultured on Matrigel, but not laminin or collagen type I or IV, formed
      spheres of condensed cells which stained with Alcian blue. Chick limb-bud
      mesenchymal cells suspended in Matrigel prepared from tumors grown in C57 mice
      aged 3, 12, or 26 months formed disks of hyaline cartilage within 2 weeks with
      wet weights of 59.1 mg, 35.7 mg, and 21.4 mg, indicating that the Matrigel from
      the old animals was less biologically active. In agreement with the in vivo data,
      Alcian blue staining of proteoglycan was over two-fold higher in micromass
      cultures supplemented with the Matrigel from young animals than in cultures
      treated with the Matrigel from old mice. A high-salt wash preparation of Matrigel
      from tumors grown in old mice increased the rate of chondrogenesis and cartilage
      production, suggesting that an inhibitor of chondrogenesis is produced by the old
      host. Thus, Matrigel contains chondrogenic activity distinct from TGF-beta or
      FGF. The aged host may produce factors that are inhibitory to mesenchymal cell
      differentiation and adversely affect cartilage formation and repair.

PMID- 8535607
TI  - Expression of collagens and decorin during aortic arch artery development:
      implications for matrix pattern formation.
AB  - The elastic matrix of the large arteries shows a high level of spatial order.
      However, the mechanisms by which such order is established and maintained are
      largely unknown. The embryonic development of the avian heart and great vessels
      provides an appropriate model to investigate these mechanisms. In control
      embryos, an elastic matrix with a high level of spatial order develops in the
      nascent great vessels. But after the normal vascular smooth muscle (VSM)
      progenitor cells in the great vessels are experimentally replaced by other VSM
      progenitor cells, the elastic extracellular matrix is congenitally disordered.
      The present study used this model to test the hypothesis that the proteoglycan
      decorin was involved in the establishment and maintenance of the normal three
      dimensional spatial order of the vascular elastic matrix. The temporospatial
      expression of decorin was analysed during development of normal vessels and in
      experimental vessels with surrogate VSM. The results showed the following: (1)
      the expression of decorin was related in time and space to the establishment of
      large helical collagen type III fibers that are characteristic of the normal
      elastic extracellular matrix; (2) in the experimental extracellular matrix there
      were few helical fibers of collagen type III, but those that were present
      remained positive for decorin; and (3) in both control and experimental vessels,
      decorin associated with neither fibers of collagen type I nor fibers of collagen
      type III in any conformation other than the large helical fibers. These data
      indicate a previously unrecognized relationship between decorin and the spatial
      order of the physiologically significant helical fibers of collagen type III.

PMID- 8535608
TI  - Trimeric assembly of collagen XII: effect of deletion of the C-terminal part of
      the molecule.
AB  - The fibril-associated-collagens-with-interrupted-triple-helices (FACITs) are
      devoid of large C-propeptides like those involved in the trimeric assembly of the
      fibrillar collagens. Under these conditions, the C-terminal non triple-helical
      domain (NC1) and the adjacent triple-helical domain (COL1) are likely to be
      responsible for the trimeric assembly of these collagen molecules. Using a
      recombinant minigene of one of the FACITs, collagen XII, we show that a deletion
      covering most of the NC1 domain, except the first seven residues containing a
      cysteine and constituting the main part of the conserved junction between the
      COL1 and NC1 domains, does not prevent the formation of trimeric disulfide-bonded
      assembly of truncated alpha chains. These results suggest that if the non triple
      helical NC1 domain is involved in the initial events governing the trimeric
      assembly, it must be through its amino acid residues participating in the
      junction. Our data confirm also the results obtained in a previous paper
      (Mazzorana et al.: J. Biol. Chem. 268:3029-3032, 1993) showing that the formation
      of disulfide bonds is dependent on hydroxylation and suggesting that the folding
      of the triple helix (or a part of it) precedes the formation of the disulfide
      bonds.

PMID- 8535609
TI  - Pressure dependence of collagen melting.
AB  - Calf skin collagen type I and interstitial collagen of the annelids Alvinella
      pompejana and Riftia pachyptila were thermally unfolded at pressures of 1 and 200
      bar. The high pressure was near the habitat pressure of the annelids which live
      in deep sea hydrothermal vents. The transition temperature increased with
      pressure by only 1.4 +/- 1 degrees C for calf skin collagen, and no pressure
      effect was detectable for the annelid collagens. The value for calf skin collagen
      agrees with prediction based on published values of the transition volume and
      transition enthalpy. The triple helices of the interstitial collagens of the
      annelids, which have melting temperatures of 46 degrees C (Alivinella pompejana)
      and 29 degrees C (Riftia pachyptila), are not further stabilized by pressure.

PMID- 8535610
TI  - The complete cDNA coding sequence for the mouse pro alpha 1(I) chain of type I
      procollagen.
AB  - The complete sequence of the cDNA for the pro alpha 1 (I) chain of mouse type I
      procollagen is presented. The encoded amino acid sequence shows 96% identity to
      the human pro alpha 1 (I) collagen chain.

PMID- 8535611
TI  - The central role of T-cells in allergic sensitization and IgE regulation.
AB  - The atopic phenotype develops on the basis of a genetic predisposition. Several
      candidate genes and chromosomal regions have been recently identified that may
      play a role in the development of allergic sensitization and total IgE
      production, including genes encoding MHC and T-cell receptor (TCR) molecules,
      cytokines and others. Genetic predisposition triggers and immunological
      dysregulation which is controlled by CD4+ T-cells. (Specialized) antigen
      presenting cells process and present allergenic peptides (T-cell epitopes) on MHC
      class II molecules to T-cells that recognize MHC plus peptide using the TCR.
      Cognate and non-cognate interaction results in T-cell activation. Selective
      stimulation of the allergen specific T-cells is the result of allergen-specific
      sensitization. These T-cells are characterized by (simultaneous) production of IL
      3, IL-4, IL-5 (and may be IL-13). These cytokines control the production of IgE
      by B cells and play a critical role in the activation and differentiation of
      effector cells of the allergic response (such as eosinophils and mast cells). In
      addition to MHC-TCR interaction and cytokine production, ligation of CD40 and
      CD40L represents an additional requirement for the production of functional IgE
      molecules. Immediate hypersensitivity responses are characterized by an early
      phase response (triggered by many mediators released from effector cells
      following allergen exposure, IgE cross-linking and activation of signal
      transduction pathways) and a late phase response that is mediated to a large
      extend by the influx of T-cells and effector cells into the site of allergic
      inflammation. Deliniation of the immunological mechanisms that result in allergic
      sensitization will contribute to the development of specific immunomodulatory
      strategies aimed to prevent the development of allergies.

PMID- 8535612
TI  - Calcium: a crucial consideration in serum-free keratinocyte culture.
AB  - This investigation was conducted when previously repeatable experimental data
      became impossible to reproduce when using keratinocytes cultured in serum-free
      medium. Differences in calcium molarity between batches of medium were identified
      as a source of variation in cultured keratinocyte populations. The susceptibility
      of cultured keratinocytes to even small alterations in calcium molarity has been
      demonstrated. 2 regular medium batches were compared with a special preparation
      of medium, devoid of calcium chloride then supplemented with a known
      concentration of calcium ions. Culture progress in each medium was assessed by:
      morphological observation, % cells expressing involucrin and proliferating cell
      nuclear antigen, cell attachment, growth rate and colony forming efficiency. In
      order to control the phenotype of cultured keratinocytes, in a reproducible
      system, it is recommended that serum-free keratinocytes medium is purchased with
      the omission of calcium chloride. Supplementation of this medium may then be made
      by the investigator to suit individual culture requirements.

PMID- 8535613
TI  - Growth and pigmentation in genetically related Cloudman S91 melanoma cell lines
      treated with 3-isobutyl-1-methyl-xanthine and beta-melanocyte-stimulating
      hormone.
AB  - 4 clonal sublines of Cloudman S91 melanoma cells, S91/mel, S91/I3, S91/6 and
      S91/amel, were evaluated for changes in growth, pigment content and plating
      efficiency during and after treatment with a cyclic-AMP phosphodiesterase
      inhibitor-melanin-stimulating agent, 3-isobutyl-1-methyl-xanthine (IBMX) plus
      beta-melanocyte stimulating hormone (beta-MSH) or IBMX alone. After combined
      treatment, increases in melanin content on day 3 were 48, 27, 11, and 2 pg/cell
      in the four cell lines respectively. In each case IBMX alone was less effective
      than IBMX plus beta-MSH. Doubling time increased and plating efficiency decreased
      with increased melanization. The increases in doubling time and decreases in
      plating efficiency were cell line dependent. The greatest rate of increase in
      doubling time and decrease in plating efficiency as a function of melanin content
      were seen in S91/amel, which produced the least pigment. The lowest rates of
      increase/decrease were seen in S91/mel, which produced the most pigment. Melanin
      pigment induced in the cells was classified as eumelanin by EPR determination.
      The differential response to induction of pigmentation makes these cell lines
      suitable models for comparative studies on the role of melanin in pigment cell
      biology.

PMID- 8535614
TI  - Diminished expression of the extracellular domain of bullous pemphigoid antigen 2
      (BPAG2) in the epidermal basement membrane of patients with generalized atrophic
      benign epidermolysis bullosa.
AB  - Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of
      junctional epidermolysis bullosa characterized by generalized skin and mucosal
      blisters that heal with atrophy; other features include alopecia, nail dystrophy,
      large melanocytic nevi, and autosomal recessive inheritance. The specific aim of
      this study was to identify an abnormality in epidermal basement membrane adhesion
      molecules in well characterized GABEB patients that would explain why these
      subjects' epidermis separates from their epidermal basement membrane. Cryostat
      sections of nonlesional skin from 8 GABEB patients in 5 different families as
      well as skin from normal volunteers (controls) were studied by indirect
      immunofluorescence microscopy using rabbit antiserum directed against a BPAG1
      fusion protein or monoclonal antibodies directed against the extracellular domain
      of BPAG2 (HD18 and 233), epiligrin (P1E1), laminin 5 (GB3), types IV and VII
      collagen, or integrin subunits alpha 2, alpha 3, beta 1, alpha 6, or beta 4. In
      these studies, monoclonal antibodies HD18 and 233 showed no reactivity and
      diminished reactivity, respectively, to the epidermal BM of all GABEB patients.
      Interestingly, in one patient, the absent or diminished reactivities of
      monoclonal anti-BPAG2 antibodies were limited to well demarcated portions of an
      otherwise intact epidermal basement membrane. Moreover, BPAG1, epiligrin, laminin
      5, types IV and VII collagen, and all integrin subunits under study were
      expressed in the same manner in both GABEB and normal human skin. These findings
      identify an abnormality in the extracellular domain of BPAG2 in the skin of GABEB
      patients. BPAG2 (type XVII collagen) is a transmembrane, hemidesmosome-associated
      molecule whose extracellular domain resides at the exact level where blisters
      develop in the skin of patients with GABEB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535615
TI  - Interaction of palladium ions with the skin.
AB  - 87 subjects sensitive to both nickel sulfate and palladium-chloride pet., were
      contemporaneously patch retested to nickel sulfate 5% pet., metallic palladium
      chloride 1% pet. and to palladium chloride 1% aq. Whilst all subjects reacted to
      nickel sulfate and palladium chloride pet., only 3 reacted to palladium chloride
      aq. No positive reactions were found to metallic palladium. The negative results
      to palladium chloride aq. are probably due to the formation of a new palladium
      ion (PdCl4)2-, achieved on adding an amount of hydrocloric acid to the aqueous
      solution of PdCl2. The findings seem to demonstrate that the allergic reaction to
      palladium depends on the arrangement of the metal electrons. The sensitization to
      palladium does not seem to be dependent on the element itself but on the
      complexes formed by the different compounds. The concomitant reactions to nickel
      and palladium ions could be dependent on the generation of similar complexes
      between the ions and the skin proteins.

PMID- 8535616
TI  - Contact sensitizers modulate mechanisms of receptor-mediated endocytosis but not
      fluid-phase endocytosis in murine epidermal Langerhans cells.
AB  - In order to define the influence of contact allergens on the fluid-phase
      endocytosis (FPE) of soluble molecules of murine epidermal Langerhans cells (LC),
      we studied the internalization of FITC-labeled bovine serum albumin (FITC-BSA),
      TRITC-labeled dextrane (TRITC-DEX) as well as horseradish peroxidase by LC. A 3
      parameter flow-cytometric technique was performed for quantification of
      internalized FITC-BSA in LC using quantum red-labeled reagents for detection of
      Ia-antigen expression by LC and propidium iodide for exclusion of dead cells from
      analysis. A temperature-dependent rapid accumulation of FITC-BSA was noticed in
      time-course studies reaching a plateau between 1 and 2 h of in vitro culture at
      37 degrees C. The quantity of FPE under stimulation with phorbol 12-myristate 13
      acetate (PMA), concanavalin A (Con A), staphylococcal enterotoxin B (SEB) and
      contact sensitizers (DNFB, Kathon CG, K2Cr2O7) as well as the irritant SLS was
      determined. Treatment of LC with PMA and Con A resulted in a significant increase
      of total FITC-BSA uptake. The contact sensitizers as well as SEB and SLS failed
      to mediate augmented fluid-phase endocytosis. By use of the pH-insensitive
      soluble marker, TRITC-DEX and a microscope photometer for evaluation these
      findings could be confirmed. This excluded any artificial influence of
      differences in pH values in endocytotic compartments which might have influenced
      the fluorescence intensity of the pH-sensitive fluorochrome FITC. For qualitative
      analysis of FPE, the intracellular distribution of internalized horseradish
      peroxidase in LC was studied. An aggregated pattern became apparent in untreated
      LC and did not change under stimulation with any of the substances used.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8535617
TI  - Porphyrin concentrations in various human tissues.
AB  - We measured the concentrations of total porphyrins and their metabolites (uro-,
      hepta-, hexa-, penta-, copro- and protoporphyrin) in various human tissues:
      liver, erythrocytes, skin, adipose tissue, and mammary gland. The porphyrin
      concentrations varied within major limits, e.g., 3.1 +/- 2.3 nmol porphyrins/g
      liver and 0.50 +/- 0.10 nmol/g erythrocytes. No significant differences were
      detectable in other tissues in comparison with liver. In all tissues, the
      predominant metabolite was protoporphyrin, followed by coproporphyrin, whereas
      only low concentrations of higher carboxylated porphyrins such as uroporphyrin
      were detectable. It is concluded that porphyrin metabolism and its regulation is
      similar in all human tissues, perhaps with some small differences in the
      erythrocytes.

PMID- 8535618
TI  - Endoscopic ultrasonography diagnosis of pancreatic cancer.
AB  - Endoscopic ultrasound (EUS) was developed for the detection of small pancreatic
      cancer because the complete demonstration of the pancreas by conventional
      ultrasonography (US) was sometimes prevented by intestinal gas and echoic
      reduction due to the deeper position of the pancreas head and tail. In this
      article, the diagnosis, staging, limitations, and hazards of EUS for diagnosing
      pancreatic cancer are described.

PMID- 8535619
TI  - Differential diagnosis of pancreatic tumors.
AB  - Endosonography is the most sensitive method to detect even small pancreatic
      tumors. A number of endosonographic criteria have been evaluated, but there are
      not specific features that allow malignant tumors to be differentiated from
      benign tumors. The role and timing of endoscopic ultrasound as part of a more
      diagnostic evaluation in patients with pancreatic tumors is not yet defined.

PMID- 8535620
TI  - Endoscopic ultrasound-guided fine needle aspiration in the diagnosis and staging
      of pancreatic tumors.
AB  - Endoscopic ultrasound (EUS) is useful in the detection of pancreatic carcinoma.
      One of its major limitations is the lack of specificity for malignancy, both for
      the primary tumor and for associated lymph nodes due to its inability to
      distinguish malignant infiltration from benign inflammation. EUS-guided fine
      needle aspiration (FNA) has now been developed, which allows for a tissue
      diagnosis of the primary tumor as well as lymph nodes, liver metastasis, and
      peritoneal/pleural fluid. The addition of EUS-guided FNA, with the specificity of
      a tissue diagnosis, to the high sensitivity and vascular assessment of EUS alone
      makes this the modality of choice for the diagnosis and staging of pancreatic
      carcinoma. The results of preliminary studies along with discussion regarding the
      technique, safety, cytologic adequacy, diagnostic accuracy, clinical utility, and
      future trends of EUS-guided FNA in pancreatic tumors are presented.

PMID- 8535621
TI  - Staging of pancreatic cancer. Analysis of literature results.
AB  - Staging of pancreatic cancer is still considered to be one of the most difficult
      areas of endoscopic ultrasound (EUS) in gastroenterology. Variable scanning
      planes to obtain images of the tumor and its relationship to surrounding
      structures and vessels as well as a variety of possible artifacts in the scanning
      of pancreatic tumors greatly contribute to these difficulties. This review
      attempts to cover all relevant aspects of the literature regarding pancreatic
      cancer staging.

PMID- 8535622
TI  - Pancreatic cancer staging. Endoscopic ultrasonography criteria for vascular
      invasion.
AB  - Endoscopic ultrasound (EUS) is the most sensitive imaging test available for
      examining the pancreas and associated structures. Small (< 2 cm) pancreatic
      malignancies can be detected with accuracy rates of more than 90%. Several EUS
      criteria have been proposed for their ability to diagnose malignant venous
      invasion. Although obstruction of a mesenteric vein and the resulting venous
      collaterals is a specific sign of unresectability, it is a rather insensitive
      parameter. As an alternative, signs of venous wall invasion, such as "irregular
      wall" have been proposed as being sensitive (67%-100%) and specific (100%) for
      malignant invasion of mesenteric veins. EUS appears to be particularly sensitive
      for detecting invasion of the portal and splenic veins. In contrast, the superior
      mesentera veins are more difficult to image with EUS and the results of staging
      of pancreatic masses demonstrate poor sensitivity (12%-17%) for detecting
      vascular invasion of the superior mesenteric vein.

PMID- 8535623
TI  - Pancreatic cancer. Influence of endoscopic ultrasonography on management and
      outcomes.
AB  - The manner in which endoscopic ultrasound (EUS) influences management of
      pancreatic cancer is reviewed in this article. The greatest impact of EUS is on
      the clinical management of small, potentially resectable tumors. Changes in
      management may not influence clinical outcome unless treatment is effective. EUS,
      however, provides an important link between the T.M. staging method and
      multimodal selective treatment concepts. The accurate T.M. staging of EUS will
      allow further advances in treatment to be applied selectively. Rational
      application of multimodal selective treatment concepts is discussed. With
      rational application of effective treatment, clinical outcome of patients with
      pancreatic cancer will improve.

PMID- 8535624
TI  - Tumors of the papilla and distal common bile duct. Diagnosis and staging by
      endoscopic ultrasonography.
AB  - In this article, the capability of endoscopic ultrasound (EUS) in the diagnosis
      and staging of carcinoma of the papilla of Vater and distal common bile duct is
      evaluated. Topics discussed include instruments and techniques, EUS diagnosis,
      preoperative staging by EUS, and diagnostic strategies.

PMID- 8535625
TI  - Proximal bile duct tumors.
AB  - This article describes the present and future clinical applications of endoscopic
      ultrasound (EUS) in the evaluation of Klatskin tumors. Topics discussed include
      instruments, investigation techniques, EUS interpretation, fine needle aspiration
      cytology, and color Doppler ultrasonography.

PMID- 8535626
TI  - Endoscopic ultrasonography in pancreatobiliary disease using radial instruments.
AB  - A review is made of clinical studies evaluating the performances of endoscopic
      ultrasonography (EUS) in pancreatobiliary disease using radial instruments. EUS
      is more accurate than conventional ultrasonography and CT scans for the diagnosis
      of solid pancreatic tumors, chronic pancreatitis, and causes of obstruction of
      the common bile duct. EUS is a promising technique for both idiopathic
      pancreatitis and cystic lesions of the pancreas.

PMID- 8535627
TI  - An update on echoendoscopy with a curved array transducer in the evaluation of
      pancreatobiliary disease.
AB  - Little information is available about echoendoscopy with an electronic curved
      array transducer for evaluation of pancreatobiliary disease. Only one study has
      been published, and two abstracts were presented at the last World
      Gastroenterology Congress in Los Angeles, California in 1994. In this article,
      the results of these studies are reviewed and compared with previously reported
      results using radial echoendoscopy systems.

PMID- 8535628
TI  - Endoscopic ultrasonography in chronic pancreatitis.
AB  - The diagnosis of chronic pancreatitis is based on clinical grounds, testing of
      pancreatic function, and imaging modalities, of which endoscopic retrograde
      cholangiopancreatography (ERCP) is considered presently as the "gold standard."
      Endoscopic ultrasound (EUS) can visualize pancreatic ductal and parenchymal
      alterations, allowing for distinguishment of the normal pancreas from different
      grades of severity of chronic pancreatitis. As a supplement to findings obtained
      by ERCP, EUS delineates a subgroup of patients exhibiting definite parenchymal
      changes despite normal duct findings on ERCP. EUS should be regarded as a
      superior diagnostic tool in the imaging of the chronically inflamed pancreas and
      should be performed early in a patient with abdominal pain of suspected
      pancreatic etiology.

PMID- 8535629
TI  - Endoscopic ultrasonography in the diagnosis and treatment of pancreatic
      pseudocysts.
AB  - This article reviews the current diagnostic and therapeutic modalities used in
      pseudocyst drainage and possible contributions of endoscopic ultrasound to this
      process. The authors conclude that EUS should improve the ability to reliably
      differentiate pseudocysts from cystic neoplasms and are excited about the new
      development that proposes to combine therapy with diagnosis.

PMID- 8535630
TI  - Common bile duct stones.
AB  - Endoscopic ultrasonography (EUS) is a sensitive and specific modality for the
      detection of choledocholithiasis. In experienced hands, it can be completely
      effective in almost all patients without significant risk. Prospective studies
      have shown that the sensitivity and specificity of EUS for the detection of
      choledocholithiasis rival that of ERCP. The clinical roles for EUS in these
      settings are currently evolving and will also likely be shaped by the continued
      forces to practice the most effective medicine.

PMID- 8535631
TI  - Endoscopic ultrasonography in gallbladder stones.
AB  - The frequency of gallbladder stones is as high as 10% in the general population
      over 50 years. Nevertheless, only 10% to 20% of patients become symptomatic. The
      diagnosis of symptomatic forms is important because treatment must be early
      before the advent of severe complications. This brief article describes
      technologic points and semeiologic endoscopic ultrasound (EUS) finding of
      gallbladder stones, analyzes the studies, and describes specific situations
      warranting the use of EUS.

PMID- 8535632
TI  - Colorectal cancer. Diagnosis of recurrence.
AB  - After curative surgery for colorectal cancer, the goal of an aggressive
      surveillance program is the detection of recurrent disease at an early and
      potentially curable stage. The routine use of endosonography (EUS) following
      surgery for colorectal cancer allows a detailed examination of the pelvis not
      previously possible without more sophisticated and expensive techniques, such as
      CT scans or MR imaging. EUS gives good information on established recurrence and
      is the single modality that allows for the detection of asymptomatic extramural
      local failures. EUS is a valuable tool for the detection of locally recurrent
      rectal cancer.

PMID- 8535633
TI  - Importance of endoscopic ultrasonography staging for treatment of rectal cancer.
AB  - Endorectal sonography should be used to stage primary rectal cancer within the
      middle and lower third of the rectum. The endosonographic staging of rectal
      cancer together with new surgical techniques has a strong impact on surgical
      decisions. Primarily, it contributes to choosing a sphincter-saving procedure.

PMID- 8535634
TI  - Endoscopic ultrasonography in inflammatory bowel diseases.
AB  - Endoscopic ultrasound (EUS) was designed for the evaluation of malignancies;
      however, its utility has been extended to the assessment of benign disorders,
      which include inflammatory bowel diseases. Topics discussed in this article
      include instruments and methods, EUS images in various inflammatory diseases,
      clinical severity and EUS typing, endoscopic grading of inflammation and EUS
      typing, extent of disease involvement and EUS typing, response to therapy and EUS
      typing, changes in EUS findings by treatment, Crohn's disease, radiation
      proctitis, ischemic colitis, tuberculosis, and mucosal prolapse syndrome.

PMID- 8535635
TI  - Endoscopic ultrasonography in inflammatory bowel disease, paracolorectal
      inflammatory pathology, and extramural abnormalities.
AB  - Endoscopic ultrasound (EUS) is easy to perform, noninvasive, and well tolerated
      in individuals with inflammatory bowel disease. In the anorectal region, the
      examination takes minimal preparation and has become a routine procedure in the
      diagnosis and therapeutic follow-up of malignant and nonmalignant disorders.
      Topics discussed in this article include techniques, abscesses, and fistulas.

PMID- 8535636
TI  - Laparoscopic ultrasonography. Has it extended the horizon?
AB  - Laparoscopic ultrasonography complements conventional radiologic evaluation of
      the biliary system at cholecystectomy. Addition of laparoscopic ultrasonography
      for staging patients with hepatic and pancreatic cancer improves accuracy and
      minimizes futile laparotomy. Dedicated laparoscopic ultrasound-guided biopsy
      devices facilitate tissue sampling. Ultrasonography will play an increasingly
      important role in laparoscopic diagnosis and treatment.

PMID- 8535637
TI  - Endoscopic ultrasound and clinical competence.
AB  - The last few years have seen substantial growth in technology, research, and
      performance of endoscopic ultrasound. Unfortunately, opportunities for training
      in EUS have not kept pace with this growth. To improve the breadth and quality of
      training in EUS, resources will need to be channeled in two directions. One is
      the development of endoscopic ultrasound training programs in academic centers.
      These would provide the expertise and the number of patients necessary to train
      selected GI fellows in EUS. The second direction is toward development of systems
      for retraining of physicians already in practice. We believe that this would
      require the development of EUS simulation systems combined with a short, intense,
      hands-on training in centers of excellence. How fast these training systems will
      develop is dependent upon market forces. If the information provided by EUS can
      be proven to reduce costs and if the results improved patient's quality of life,
      the development of training programs for EUS would accelerate markedly.

PMID- 8535638
TI  - Radical Intervention in Early Rheumatoid Arthritis. The Case for Enteric-Coated
      Sulphasalazine, Methotrexate and Combination Regimes. Proceedings of a workshop.
      Camogli, Italy, September 1994.

PMID- 8535639
TI  - How and when should combination therapy be used? The role of an anchor drug.
AB  - Most patients with rheumatoid arthritis do not achieve a complete response to
      monotherapy; some achieve a sub-optimal response and others become resistant to
      therapy and escape from control after an initial good response. It is essential
      to recognize those with an incomplete response early and to introduce combination
      therapy promptly so as to induce remission and minimize joint damage and
      disability. The main concern about combination therapy has been the risk of
      additive or synergistic toxicity. The aim is therefore to choose drugs that are
      the least toxic and that also have a rapid and sustained action. Sulphasalazine
      (SASP) possesses these properties; it has a mild toxicity profile and good long
      term tolerability. Most adverse events occur during the first few months of
      therapy and accumulative toxicity on stable maintenance doses is rare. It also
      has a rapid onset of action and sustained efficacy. On these grounds we recommend
      that SASP is used in combination therapy as the 'anchor drug' to which other
      drug(s) can be added sequentially. This sequential regimen allows those patients
      who respond to monotherapy to be identified, and gives flexibility of dose
      control so that the drugs can be tailored to the individual patient. Combination
      therapy may have real advantages in inducing remission and preventing resistance
      to therapy. it also has the potential for long-term disease modification.

PMID- 8535640
TI  - Combining sulphasalazine and methotrexate in rheumatoid arthritis: early clinical
      impressions.
AB  - The use of combinations of second line antirheumatic agents (SLAs) is increasing.
      There are several reasons for combination therapy, e.g. the unsatisfactory
      effects of single therapy. Strategies for combining SLAs are to begin with
      combinations, or to add one or more agents to another. The strategy of adding one
      agent to another is illustrated by a study of 40 patients having insufficient
      effect from sulphasalazine (SASP). Patients were randomized between methotrexate
      (MTX) and the combination of SASP and MTX. The patients were evaluated by a
      single observer in an open design. The follow-up was 24 weeks. The mean decrease
      in disease activity score was significantly greater and occurred earlier in the
      combination group. This favourable response was also present in the other
      efficacy variables. The incidence of toxicity was equal in both groups. These
      results support the strategy of adding MTX to SASP when combining these second
      line antirheumatic drugs.

PMID- 8535641
TI  - Combination of sulphasalazine and methotrexate in the management of rheumatoid
      arthritis--view based on personal clinical experience.
AB  - Over the past fifteen years, there has been increasing interest in the use of
      combinations of medications to better suppress the inflammatory process that
      leads to progressive disability in most rheumatoid arthritis patients. We have
      been evaluating the combination of sulphasalazine and methotrexate for the last 8
      years. Although these data are uncontrolled, our experience would suggest that
      this combination is well tolerated. Furthermore, flares of disease occurring with
      attempts to withdraw either of the two agents suggest that the combination may be
      effective when the use of these agents individually has not.

PMID- 8535642
TI  - Sulphasalazine, sulphapyridine or 5-aminosalicylic acid--which is the active
      moiety in rheumatoid arthritis?
AB  - Sulphasalazine is cleaved into 5-aminosalicylic acid and sulphapyridine by
      colonic bacteria. The bulk of evidence favours sulphapyridine rather than 5
      aminosalicylic acid as the active moiety (as well as the main producer of side
      effects) though a therapeutic action from the 30% of sulphasalazine that is
      absorbed unaltered also cannot be excluded.

PMID- 8535643
TI  - The history of the use of sulphasalazine in rheumatology.
AB  - Sulphasalazine was initially used more than 50 yr ago to treat inflammatory
      arthritis but fell into disuse, only to be revived 25 yr ago for rheumatoid
      arthritis. Since then its place as a second-line agent has been established and
      its toxicity profile has been outlined. Subsequently, its use has been widened to
      include other inflammatory rheumatic diseases, with strong suggestions that it
      may be useful for several indications. The history of its initial use, its
      reintroduction and the establishment of its place in modern rheumatology are
      reviewed.

PMID- 8535644
TI  - Practical clinical pharmacology and drug interactions of low-dose methotrexate
      therapy in rheumatoid arthritis.
AB  - The clinical pharmacology and clinically important drug interactions of
      methotrexate (MTX) are reviewed. The points discussed are as follows. (a) The
      bioavailability of oral preparations of MTX is approximately 15-20% lower than
      that of intramuscular or intravenous MTX, although there is great variability in
      relative bioavailability. (b) Protein-binding displacements are unlikely to be of
      importance with this low-to-medium protein-binding drug. Because MTX is
      polyglutamated and remains within cells, dialysis is unlikely to be an effective
      mode of elimination. The principal excretory pathway of MTX is via the kidneys,
      although some is also excreted through the bile. These facts imply that: (i) MTX
      needs to be used with extreme caution, if at all, in the face of renal
      insufficiency; (ii) cholestyramine may be used to enhance the biliary excretion
      of MTX; and (iii) probenecid may be a cost-effective way to increase the efficacy
      of MTX. (c) Although aspirin inhibits MTX clearance more than other non-steroidal
      anti-inflammatory drugs (NSAIDs), clinical toxicity of aspirin is not
      significantly greater than that of other NSAIDs. In all cases this negative
      interaction is very rare (although, of course, it needs to be considered at all
      times). (d) It is possible that corticosteroids inhibit MTX metabolism, although
      this requires significant research. (e) Trimethoprim-sulphamethoxazole (TS)
      toxicity is well documented and may be related to synergistic anti-folate effects
      of MTX and TS. (f) Folic acid decreases MTX toxicity, possibly through an effect
      on dihydrofolate reductase.

PMID- 8535645
TI  - Possible mechanisms of action of methotrexate in patients with rheumatoid
      arthritis.
AB  - Methotrexate has been reported to be effective in various animal models of
      arthritis as well as a variety of human disorders without a shared pathogenesis.
      Reports have emerged of the effect of the drug on lymphocytes, cytokines,
      leukotrienes, neutrophils, as well as a large variety of intracellular
      biochemical pathways. At present, it is not possible to identify which of the
      many possible mechanisms of action are relevant to its action when used in
      patients with rheumatoid arthritis (RA). More definitive insights may have to
      await a better understanding of the immunopathogenesis of RA.

PMID- 8535646
TI  - The antirheumatic agents sulphasalazine and methotrexate share an anti
      inflammatory mechanism.
AB  - Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for
      second-line therapy of rheumatoid arthritis (RA). Although SASP and MTX are
      commonly used, the mechanism(s) by which these drugs control the inflammation
      that characterizes RA have remained obscure. Results from my laboratory indicate
      that these agents share a mode of action; the anti-inflammatory effects of both
      SASP and MTX are due, in both in vitro and in vivo studies, to their capacity to
      enhance adenosine release at inflamed sites. This mode of action suggests that
      the development of agents that directly alter adenosine metabolism may lead to
      new, more effective and safer antirheumatic drugs than those currently available.

PMID- 8535647
TI  - Clinical efficacy of sulphasalazine--a review.
AB  - This review of the use of sulphasalazine (SASP) in the therapy of rheumatoid
      arthritis refers to the placebo-controlled trials of SASP and the randomized
      comparative studies with other second-line drugs that have been published over
      the past decade. The questions relating to appropriate selection of patients for
      this treatment and the possible relevance of drug interactions are addressed. The
      favourable effect of SASP on functional, radiological and extra-articular outcome
      measures is highlighted, as is the reproducibility of published studies. Finally,
      the results from combination studies and meta-analyses are outlined.

PMID- 8535648
TI  - Long-term usage and side-effect profile of sulphasalazine in rheumatoid
      arthritis.
AB  - In a cohort of patients with early rheumatoid arthritis, sulphasalazine (SASP)
      was mainly given as a first-choice second-line agent. SASP resulted in a
      significantly better survival rate compared with hydroxychloroquine, which is
      also given as a first-choice agent. When the survival rate of SASP was compared
      with that of aurothioglucose, both given as second-choice agents, again, a
      statistically significant better survival rate was found for SASP. In 9% of the
      patients, SASP could be withdrawn as a complete remission was obtained. Adverse
      reactions occurred mainly during the first 3 months of treatment, and in 20% of
      patients these were severe enough to stop treatment. Gastrointestinal adverse
      reactions were most frequently observed, and all adverse reactions were
      completely reversible after treatment withdrawal. Treatment was started with a
      standard dose of 2000 mg/day. However, in approximately 30% of the patients, this
      dose was increased up to 3000 mg/day and, in another 30%, the dose was decreased
      to 1,500 or 1,000 mg/day.

PMID- 8535649
TI  - Efficacy of methotrexate in rheumatoid arthritis.
AB  - Methotrexate (MTX), an antifolate agent, has been used in the treatment of
      rheumatoid arthritis (RA) for over two decades. Open clinical studies and short
      term, randomized, placebo-controlled studies demonstrate the efficacy of MTX in
      active RA. Long-term prospective studies, including two of over 7 yr duration,
      report a sustained response and a corticosteroid-sparing effect. Comparative
      studies demonstrate superior efficacy to auranofin, azathioprine and cyclosporin
      A. A highly favourable retention rate with the drug has been noted in large
      studies from academic and community-based practices. Radiographic studies suggest
      a slowing of radiographic progression with the compound. MTX has become an
      accepted and widely used treatment for active RA.

PMID- 8535650
TI  - Adverse events in methotrexate-treated rheumatoid arthritis patients.
AB  - Methotrexate (MTX) is an antifolate that has been in use for the treatment of
      rheumatoid arthritis (RA) since the early 1980s. Its efficacy has been clearly
      documented [1-4] and its administration early in the course of the disease is now
      generally accepted [5]. Side-effects from low weekly pulse MTX have been reported
      [1-6] and it was our initial experience that toxicity, rather than lack of
      efficacy, was the major factor limiting its clinical use [7]. However, when
      compared with other disease-modifying antirheumatic drugs, its toxicity appears
      to be comparable to that of antimalarials [8, 9]. The purpose of this paper is to
      discuss the possible mechanisms responsible for toxicity due to MTX used at low
      weekly pulse doses for the treatment of RA, as well as the different toxic
      manifestations reported in the literature.

PMID- 8535651
TI  - Long-term outcomes in rheumatoid arthritis.
AB  - Long-term outcomes in the majority of patients with established rheumatoid
      arthritis (RA) include radiographic progression, severe functional declines, work
      disability and premature mortality. These outcomes have been recognized primarily
      in long-term clinical observational studies, which also indicate that most
      courses of traditional therapies are discontinued within 2 yr. Severe long-term
      outcomes in RA are predicted more effectively by sustained inflammatory activity
      than by any measure of baseline activity at a single point in time. Aggressive
      efforts to control inflammatory activity prior to irreversible damage would
      appear to be a reasonable strategy for treatment of RA.

PMID- 8535652
TI  - Sulphasalazine: mechanism of action in rheumatoid arthritis.
AB  - Sulphasalazine a drug used for the treatment of rheumatoid arthritis (RA) shows a
      wide range of biological activities all of which might contribute to the
      beneficial clinical effect seen during treatment of RA. This review summarizes
      some of the biological activities and discusses these in context of possible
      modes of action of the drug. Sulphasalazine has been described as an
      antibacterial drug, an anti-inflammatory drug or as an immunomodulator. From the
      reviewed data it is concluded that the effects of sulphasalazine on various
      immunological processes, are of outstanding importance for its mode of action.

PMID- 8535653
TI  - Joint erosions and patients with early rheumatoid arthritis.
AB  - The development of changes on X-rays in patients with rheumatoid arthritis (RA),
      as described in the literature, is presented. Prospective studies on patients
      with early disease show that approximately 75% of the patients have joint
      erosions. The majority of patients develop the first erosions during the first 2
      yr of the disease. The rate of progression, expressed as newly eroded joints or
      increase in radiographic damage, is highest during the early years of the
      disease. Joints in the feet erode earlier than those in the hands. Moreover, more
      joints are affected in the feet than in the hands. Exact data on the involvement
      of large joints are scarce, but the progression of RA in small and large joints
      correlates well. Over half of the patients develop an involvement of the cervical
      spine during the first 10 yr of the disease. The percentage of patients with
      cervical subluxation increases steeply with disease duration.

PMID- 8535654
TI  - Short-term outcomes in recent-onset rheumatoid arthritis.
AB  - Comparing outcomes of different therapeutic interventions is a vital part of
      progress in rheumatology, and considerable advances have been made in recent
      years toward consensus in outcome assessment. The conflicting results of
      longitudinal and cross-sectional studies of rheumatoid arthritis (RA) have been
      due, at least in part, to variable study designs. The few reports of prospective
      studies of recent-onset RA have been limited by the paucity of numbers at follow
      up. Information on outcome and prognostic factors in RA requires prospective
      studies on large numbers of patients recruited from an early stage. The
      practising clinician needs easily applied prognostic factors for the effective
      management of patients with RA. Predicting erosive disease has been more
      successful than predicting functional outcome, but neither, as yet, have the
      accuracy required in early disease for the use of single or combined powerful,
      and potentially more toxic, second-line (disease-modifying) therapies. The Early
      Rheumatoid Arthritis Study (ERAS) was formed to study these aspects in more
      detail with large numbers of patients. Initial findings have shown that 15% of
      patients went into sustained clinical remission early, response to the first
      disease-controlling drug was satisfactory in 70% of patients and functional
      measures at presentation were by far the most predictive variables for physical
      disability at 3 yr.

PMID- 8535655
TI  - Therapeutic approaches for early rheumatoid arthritis. How early? How aggressive?
AB  - A critical question for the management of patients with rheumatoid arthritis (RA)
      is the timing and extent of pharmacological intervention. There is good evidence
      that early disease is important, and data showing early intervention have
      particular advantages. However, in the past, several difficulties have arisen
      with this approach. The availability of patients seen in early arthritis clinics,
      the ability to predict outcome and the development of new methods of monitoring
      have made a large difference to the possibilities for therapy. This article
      describes why it is now reasonable to treat patients who have 'standard' RA with
      a disease-modifying antirheumatic drug (DMARD) at presentation. In those patients
      with a worse prognosis, a more aggressive regime is justified. For those who do
      not fulfil criteria laid down by the American College of Rheumatologists,
      treatment with a DMARD may still be appropriate on a cost-benefit analysis.
      Studies addressing these issues are currently being undertaken.

PMID- 8535656
TI  - Clinical trial design for evaluating combination therapies.
AB  - Because the differences in efficacy between a disease-modifying antirheumatic
      drug (DMARD) combination and its constituent drugs are likely to be smaller than
      those between placebo and the single DMARDs, it has been difficult to prove that
      any combination of DMARDs has either additive or synergistic benefit. The
      discriminatory power of the study design can be enhanced by careful attention to
      the details of patient selection, study design and duration, and choices of
      primary outcome measures and analytical methods. Use of the American College of
      Rheumatology (ACR) 'core set' of outcome measures and the proposed ACR
      'definition of improvement' for rheumatoid arthritis (RA) clinical trials, with
      intent-to-treat analysis, in a balanced, prospective, double-blind randomized
      clinical trial of 1-2 yr duration will optimize the chances of discriminating
      between the clinical benefit of the combination and its components if a real
      difference is present.

PMID- 8535657
TI  - Overview of combination second-line or disease-modifying antirheumatic drug
      therapy in rheumatoid arthritis.
AB  - This article discusses the use of combinations of disease-modifying antirheumatic
      drugs (DMARDs) in the treatment of rheumatoid arthritis (RA). Patients with RA
      have a disease that can be disabling and life threatening and current therapies
      do not prevent these complications. The need for more aggressive therapy is
      apparent. The rationale for combinations of DMARDs is explored and the efficacy
      and safety of reported combinations is summarized. The variables to be reviewed
      in selecting a combination of DMARDs are examined. Newer approaches employing
      multiple DMARDs will be considered.

PMID- 8535658
TI  - Cost-effectiveness analysis: are the outputs worth the inputs?

PMID- 8535659
TI  - Immunotherapy of a plasmacytoma with attenuated salmonella.
AB  - An attenuated strain of Salmonella typhimurium, SL3235, developed as a prototypic
      typhoid vaccine, is shown to retard growth of a murine plasmacytoma, TEPC-183,
      and to prolong survival of tumor-bearing mice. Live salmonella, but not acetone
      killed organisms, had antitumor activity. The immunotherapeutic effect was
      demonstrable when the tumor was injected intralesionally or intraperitoneally.
      Increased survival, longer mean time to death, and retardation of tumor growth
      were found when the salmonella were given intralesionally as late as the sixth
      day post-tumor injection. Timing of salmonella inoculation, as well as the
      salmonella dose, had an effect on treatment efficacy. Injection of salmonella
      intraperitoneally exerted a strong antitumor effect when given as late as the
      third day post-tumor inoculation. The highest dose (2 x 10(6)) of salmonella was
      less effective than doses 10- or 100-fold lower. TEPC-183 plasmacytoma is rapidly
      growing and highly immunosuppressive, so the ability of the salmonella to exert
      therapeutic activity against it is a measure of the potency of the vaccine. These
      observations are of interest, as they show that a genetically engineered,
      avirulent strain of Salmonella has immunotherapeutic properties similar to those
      of BCG and other biological response modifiers, and might have clinical potential
      as an antitumor agent.

PMID- 8535660
TI  - Assessment of proton magnetic resonance spectroscopy of blood serum as a
      diagnostic tool in bone marrow transplantation.
AB  - The use of proton high-resolution magnetic resonance spectroscopy (MRS) allows
      the rapid detection and quantitation of modification in the blood serum metabolic
      profiles in haematooncological patients. This study examines the feasibility of
      using proton MRS as a diagnostic tool in predicting the outcome of bone marrow
      transplantation (BMT) at the earliest possible date. Proton spectra of serum
      samples from 18 BMT patients (11 autologous-BMT and seven allogeneic-BMT), six
      hematooncological patients that did not undergo BMT and six normal individuals
      were recorded at 400 MHz. A longitudinal MRS study was carried for these groups
      and the data were evaluated for statistical significance. It was determined that
      the MRS results, taken at different time points before and after the BMT
      treatment, are statistically significant. However, no significant difference was
      observed in the MRS parameters between the transplanted patients and the control
      patients. We could not obtain significant correlation between the MRS results and
      the immunoglobulin level, engraftment parameters or the age, sex, stage of basic
      disease, conditioning protocols, transplant type, post transplant complications
      (including death) and outcome.

PMID- 8535662
TI  - Levels of soluble interleukin-2 receptors are predictive of response in patients
      treated with interleukin-2 and lymphokine-activated killer cells.
AB  - Soluble interleukin-2 receptor (sIL-2R) alpha (CD25) levels were serially
      determined in the sera of 20 patients who had undergone adoptive immunotherapy
      with high-dose IL-2 and lymphokine-activated killer (LAK) cells for various types
      of metastatic solid tumors or Hodgkin's disease. The treatment course consisted
      of 5 days of high-dose IL-2 priming followed by the collection of peripheral
      blood leukocytes by leukapheresis, and in vitro activation of mononuclear cells
      with IL-2, and the subsequent infusion of such prepared LAK-cells together with
      IL-2. sIL-2R levels increased in all patients following IL-2 administration, and
      the ratio of baseline sIL-2R levels to those measured after 5 days of IL-2 was
      significantly correlated with pre-IL-2 levels (p = 0.016) in that higher pre-IL-2
      levels resulted in a larger increase upon IL-2 administration. In terms of
      treatment outcome, the variables analysed included sIL-2R levels, total IL-2
      doses administered, the expression of membrane-bound CD25 on in vitro cultured
      cells (pre- and post-IL-2 exposure), the total number of LAK-cells infused and in
      vitro cytotoxic activity of LAK-cells against the natural killer cell-resistant
      cell line Daudi. In a multivariate analysis, low baseline sIL-2R levels (p =
      0.095) and high in vitro cytotoxic activity of LAK-cells against Daudi cells (p =
      0.082) were jointly associated with response. Our data suggest that serum sIL-2R
      levels provide a fast and noninvasive parameter for predicting the response in
      patients treated with IL-2 and LAK-cells.

PMID- 8535661
TI  - Phase II trial of chemotherapy, external and intraluminal radiation plus surgery
      for oesophageal cancer.
AB  - A pilot study was performed to assess the feasibility of combining 5
      fluorouracil, recombinant alpha-2b-interferon, external radiation therapy and
      intraluminal high dose rate brachytherapy with surgery in patients with locally
      advanced esophageal carcinoma. 5-fluorouracil, 750 mg m-2, was administered via
      continuous 5-day infusion beginning day 1 and weekly thereafter; interferon, 10
      mu subcutaneously, was administered three times per week beginning day 1 and
      sargramostin, 5 micrograms kg-1, was administered on days without 5-fluorouracil.
      External radiation began on day one using 1.5 daily fractions to 55.5 Gy.
      Intraluminal brachytherapy was delivered concomitantly once each week for 5
      fractions of 4 Gy. None of the first eight patients went to surgery. The external
      radiation was changed to 1.5 Gy BID to 45 Gy followed by BID intraluminal
      radiation to 15 Gy. Of the last four patients, there was one case of radiation
      myelitis. It was found that successful surgery was not possible and excessive
      toxicities, including radiation myelitis, occurred with this aggressive regimen.

PMID- 8535663
TI  - Successful matched unrelated transplantation from a donor with idiopathic
      thrombocytopenic purpura (ITP).
AB  - The case of a 5 year old male is described who had acute myeloblastic leukaemia
      (AML M5) and was in third remission when he underwent an allogeneic T cell
      depleted bone marrow transplantation (BMT). The bone marrow was from an HLA
      matched unrelated donor (MUD) who suffered from chronic idiopathic
      thrombocytopenic purpura (ITP). In spite of this, the patient had rapid platelet
      engraftment post BMT (> 50 x 10(9) l-1 on day 20). He is now 12 months post
      transplantation and has normal platelet counts, without any clinical or
      laboratory evidence of ITP. Autoimmune manifestations such as ITP occurring in
      bone marrow recipients following BMT have been previously reported. Furthermore,
      severe and protracted thrombocytopenia is a known complication following MUD
      transplantation and with its respective high risk of graft versus host disease
      (GVHD). In this case, no signs of ITP could be detected in the recipient despite
      the fact that the donor had ITP. Our data suggest that in the absence of an
      alternative choice, a person with ITP should be considered as an appropriate
      donor for transplantation.

PMID- 8535664
TI  - Increased LAK and T cell activation in responding renal cell carcinoma patients
      after low dose cyclophosphamide, IL-2 and alpha-IFN.
AB  - Immunologic monitoring of cancer patients treated with IL-2 might help to
      determine functions of significance for the clinical outcome. Some immune
      functions in patients with advanced renal cell carcinoma were studied during
      treatment with low dose cyclophosphamide, alpha-interferon and IL-2.
      Cyclophosphamide (500 mg m-2) was given day 1, and alpha-interferon (3 x 10(6) u
      i.m.) and continuous infusion of IL-2 (18 x 10(6) u m-2 day-1) for days 4-9. The
      cycle interval was 3 weeks. Two to six cycles were given. Eleven patients entered
      the study. One patient achieved a partial remission, two patients had a minor
      response and four had a stable disease ('responding patients'). NK cell activity
      (K562) increased in all patients while LAK cell activity (against a renal cell
      carcinoma cell line, A498) was significantly augmented only in responding
      patients. In the responder group, there was a significant increase in CD3+/HLA
      DR+ T-cells. In parallel, there was a significant decrease in CD45RA+ cells as
      well as in the CD4/CD8 ratio. These data might indicate an expansion of activated
      T cells with a reduction of cells with a suppressor phenotype in responding
      patients. The results corroborate the importance of activation of LAK cells and T
      cells during IL-2 therapy of cancer patients.

PMID- 8535665
TI  - Multidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content
      of leukemic cells from patients with acute leukemia.
AB  - The clinical relevance of multidrug resistance gene (mdr1) expression in tumor
      cells remains largely unclear. Conflicting results regarding mdr1 gene expression
      and clinical outcome have been obtained. Little is known about regulation of mdr1
      gene expression, and the conflicting results might be explained by the fact that
      mdr1 RNA levels do not reflect expression at the protein level. The aim of the
      present study was to investigate the relationship between mdr1 RNA levels and P
      glycoprotein (Pgp) content of leukemic cells from patients with acute myelogenous
      or lymphocytic leukemia. Mdr1 RNA levels were determined by a quantitative RNA
      RNA solution hybridization method, and Pgp by Western blot technique with
      enhanced chemiluminescence for immunodetection. Pgp was detected in 14/14
      leukemic cell samples while mdr1 RNA was detectable (> 0.15 copies/cell) in cells
      from only six out of the 14 patients. Mdr1 RNA levels did not correlate with the
      Pgp content of leukemic cells (r = 0.284, p = 0.306). Relapsed leukemias had
      significantly (p = 0.016) higher levels of Pgp than de novo untreated leukemias
      (the mean and SD optical density units were 0.56 +/- 0.18 and 0.25 +/- 0.17
      respectively) while no difference was found in RNA levels. The findings support
      post-transcriptional level regulation of mdr1 gene expression and stress the
      importance of accurate determinations of the Pgp content of tumor cells in
      studies of the relationship between mdr1 gene expression and clinical outcome.

PMID- 8535666
TI  - Gynaecologic effects of tamoxifen.
AB  - Tamoxifen, an estrogen antagonist, is widely used as adjuvant therapy in patients
      with breast cancer. Its efficacy in increasing survival and reducing recurrence
      rates has been demonstrated in several European and American studies. However,
      its effects appear to be tissue specific. Tamoxifen exerts an estrogen effect
      (agonist) on the endometrium, myometrium and vagina. An increase in uterine
      cancer has been confirmed in several placebo-controlled clinical trials. Due to
      the widespread use of this drug, it is timely to review the gynecologic effects
      of tamoxifen.

PMID- 8535667
TI  - Adhesive receptors expressed by tumor cells and platelets: novel targets for
      therapeutic anti-metastatic strategies.
AB  - In vitro and in vivo studies have demonstrated that adhesive interactions between
      tumor cells and platelets may play a central role in the metastatic process.
      Ultrastructural studies have demonstrated that platelets appear to enhance the
      development of arrested tumor emboli into a secondary metastatic colony. Platelet
      adhesive glycoprotein receptors and their immunorelated counterparts expressed by
      tumor cells participate in tumor-induced platelet aggregation, which may be an
      early step in the development of a metastatic lesion. Platelet anti-adhesive
      agents have been demonstrated to reduce metastases in rodent models. Although
      tumor adhesive glycoproteins have yet to be fully characterized, specific
      inhibition of their functional sites could constitute a forthcoming strategy for
      effective inhibition of metastases.

PMID- 8535668
TI  - Transurethral microwave thermotherapy: an evolving technology in the treatment of
      benign prostatic enlargement.

PMID- 8535669
TI  - Renal function up to 16 years after conduit (refluxing or anti-reflux
      anastomosis) or continent urinary diversion. 1. Glomerular filtration rate and
      patency of uretero-intestinal anastomosis.
AB  - OBJECTIVE: To evaluate the glomerular filtration rate (GFR) and incidence of
      anastomotic stenosis in patients with urinary diversion by ileal or colonic
      conduit (refluxing or anti-reflux uretero-intestinal anastomosis) or with a
      continent caecal reservoir. PATIENTS AND METHODS: All conduit urinary diversions
      performed from 1977 to 1984 were randomized by type (ileal or colonic) and by the
      method of ureteric implantation (with or without anti-reflux technique). In
      continent caecal reservoirs anti-reflux implantation was used for both ureters.
      Total and separate GFR were measured pre-operatively and after a mean follow-up
      of 123 months (range 36-198) with 51Cr-EDTA and scintillation renography.
      RESULTS: Of the 56 evaluable patients, 18 had an ileal and 20 a colonic conduit,
      and 18 had a continent reservoir. The total mean GFR fell from 88 to 71 mL/min in
      the ileal group, from 84 to 65 mL/min in the colonic group and from 100 to 85
      mL/min in the reservoir group. Separate GFR did not differ significantly between
      kidneys with and without reflux protection in the patients with a conduit
      diversion. Strictures occurred in 15 uretero-intestinal anastomoses and were
      unrelated to the mode of ureteric implantation (in the conduit groups). Renal
      function improved after ureteric reimplantation in six of seven kidneys, but
      after balloon dilatation in only one of five. CONCLUSION: GFR fell moderately in
      all three groups, with no significant intergroup difference, and the continent
      caecal reservoir compared favourably with conduit diversion. The fall in separate
      GFR did not differ significantly between kidneys with and without reflux
      protection. Surgical exploration of uretero-intestinal stenosis is recommended if
      renal function is threatened.

PMID- 8535670
TI  - Renal function up to 16 years after conduit (refluxing or anti-reflux
      anastomosis) or continent urinary diversion. 2. Renal scarring and location of
      bacteriuria.
AB  - OBJECTIVE: To evaluate the importance of refluxing versus anti-reflux ureteric
      implantation for the development of renal scarring in patients with a conduit or
      continent urinary diversion and for the incidence of bacteriuria in the upper
      urinary tract of patients with a conduit. PATIENTS AND METHODS: Renal
      scintigraphy using 99mTc-dimercaptosuccinic acid was performed on 32 of 37
      evaluable patients from a prospective, randomized study at a mean of 150 months
      (range 102-198) after urinary diversion. In five patients with a conduit
      diversion and unilateral renal scarring, urine was samples for culture from the
      proximal end of the conduit and from both renal pelvices by direct percutaneous
      aspiration. RESULTS: Of 35 renal units (18 patients), studied after conduit
      diversion, scarring was found in 11 (two grade I, six grade II and three grade
      III) of 17 with refluxing anastomosis and in six (one grade I, four grade II and
      one grade III) of 18 with anti-reflux anastomosis (P = 0.06). Of 25 renal units
      (14 patients) after continent diversion, 16 showed scarring (seven grade I and
      nine grade II). Bacteriuria was found in four of five upper urinary tracts with a
      refluxing anastomosis, but in only one of five with an anti-reflux anastomosis.
      In these five patients scarring was present in all kidneys with refluxing
      anastomosis. CONCLUSION: Anti-reflux ureteric anastomosis seems to be important
      for preventing scarring and bacteriuria in the upper urinary tract of patients
      with a conduit urinary diversion. Despite the anti-reflux technique of ureteric
      implantation, most patients with a continent reservoir had renal scarring, though
      it was generally less severe than in patients with a conduit urinary diversion.

PMID- 8535671
TI  - Clinical outcome and quality of life following enterocystoplasty for idiopathic
      detrusor instability and neurogenic bladder dysfunction.
AB  - OBJECTIVE: To study the long-term outcome of patients undergoing
      enterocystoplasty. PATIENTS AND METHODS: The study comprised 48 patients (17 men
      and 31 women; mean age 46 years) who underwent enterocystoplasty for idiopathic
      detrusor instability (DI, 35 patients) or neurogenic bladder dysfunction (13
      patients). Symptoms were scored from 0 to 14 and the overall outcome and generic
      quality of life were assessed using a Visick grading system (groups A to E) and
      the Nottingham Health Profile (NHP). These assessments were carried out before, 3
      months after operation and at the final follow-up (38 +/- 18 months, range 13
      78). Urodynamic studies were performed before and after operation. RESULTS: No
      patient died after operation and there was minimal early morbidity. Late
      complications (> 30 days) included incisional hernia (3), anastomotic perforation
      (1), calculus formation (1) and urethral stricture (1). Clean intermittent self
      catheterization (CISC) was performed by 36 (75%) patients. Early symptomatic
      outcome was good in 40 (83%) patients, moderate in seven (15%) and unsatisfactory
      in one (2%) patient. The mean symptom scores before and 3 months after surgery
      were 10 (range 2-14) and 3 (range 2-14), respectively (P < 0.001). There was a
      significant increase in total bladder capacity (307 +/- 140 to 588 +/- 217 mL; P
      < 0.001) and bladder compliance (37 +/- 50 to 169 +/- 162 mL/cm H2O; P < 0.001).
      DI persisted in 15 (31%) patients. NHP scores revealed significant improvements
      in all domains. Final assessment showed a less satisfactory situation, with
      recurrent urinary tract infection (UTI) in 17 (37%) patients, a need for long
      term antibiotic therapy in seven (15%) and a change in bowel habit in 15 (33%)
      (13 DI, two with neurogenic bladder dysfunction). CISC was performed by 39 (85%)
      patients. The long-term outcome was good or moderate in 12 patients (92%) with
      neurogenic bladder dysfunction and good or moderate in only 19 patients (58%)
      with DI. CONCLUSION: Clam enterocystoplasty remains an effective management
      option in some patients with DI, but most patients with neurogenic bladder
      dysfunction do well. The procedure is, however, associated with long-term
      complications such as disturbance of bowel habit and recurrent UTIs, which impair
      the outcome in the long-term in patients with DI despite general improvements in
      irritative bladder symptoms.

PMID- 8535672
TI  - Further clinical experience with the ileal W-neobladder and a serous-lined
      extramural tunnel for orthotopic substitution.
AB  - OBJECTIVE: To report on the functional results following orthotopic substitution
      using an ileal W-neobladder with an extramural serous-lined tunnel for reflux
      prevention. PATIENTS AND METHODS: Sixty men (mean age 46 years) underwent a one
      stage radical cystoprostatectomy and an ileal W-neobladder for invasive bladder
      cancer. The technique entails the creation of two serous-lined extramural tunnels
      in a detubularized ileal W-bladder fashioned from 40 cm of the terminal ileum.
      Fifty-one patients were evaluable, with a minimum follow-up of 2 years.
      Evaluation of patients included clinical, radiographic and urodynamic studies.
      RESULTS: There was no operative mortality and no gross morbidity. The upper
      tracts remain unchanged or improved in 97% of the implanted renal units. Reflux
      was not observed in any patient. The incidence of day and night continence was 90
      and 80%, respectively. CONCLUSION: The technique provides a non-obstructed
      unidirectional uretero-ileal re-implantation, in a low-pressure system
      constructed from a short ileal segment. No staples were required.

PMID- 8535673
TI  - Urinary tract obstruction and nephrostomy drainage in pelvic malignant disease.
AB  - OBJECTIVE: To determine the survival of patients after percutaneous nephrostomy
      drainage (PND) for obstructive uropathy secondary to pelvic malignant disease.
      PATIENTS AND METHODS: The records of 77 patients undergoing PND for obstructive
      uropathy were reviewed. Patients were classified according to the nature of the
      obstructing lesion: Group I (primary untreated malignancy, 31 patients); Group II
      (recurrent malignancy with further treatment, 15 patients); Group III (recurrent
      malignancy with no further treatment, 12 patients); and Group IV (benign disease
      as a consequence of previous treatment, 19 patients). Outcome was assessed by
      survival over a mean follow-up of 20 months (range 2 days-8.3 years). RESULTS:
      Overall median survival was 26 weeks, with a 5-year survival of 22%. The survival
      in Groups I and II was not significantly different (median survival 27 and 20
      weeks, respectively; 5-year survival, 10% and 20%, respectively). Group III
      patients had a poor prognosis (median survival 6.5 weeks) with no patient
      surviving beyond one year, whilst Group IV patients fared best with a 5-year
      survival of 64%. The commonest primary tumour type was carcinoma of the cervix
      (42 patients), and these patients were analysed as a subset. Benign post
      radiation fibrosis was found in 16 of 27 patients (59%). Survival was related to
      the diagnostic group. CONCLUSION: The nature and extent of the obstructing lesion
      and its potential for further treatment are the major determinants of post
      nephrostomy survival. Every effort should therefore be made to identify the
      nature of the obstruction before deciding on PND.

PMID- 8535674
TI  - Flow-cytometric DNA analysis of paraffin-embedded renal cell carcinoma tissue
      from patients treated by parenchymal-sparing surgery.
AB  - OBJECTIVE: To determine the utility of deoxyribonucleic acid (DNA) ploidy
      pattern, detected by flow cytometry, in predicting the outcome of renal cell
      carcinoma (RCC). PATIENTS AND METHODS: DNA content was retrospectively assessed
      by flow cytometry in 28 primary paraffin-embedded RCCs from 24 patients (16 men
      and eight women, mean age 61.9 years, range 40-89) who had undergone renal
      parenchymal-sparing surgery. RESULTS: Tumour recurred locally in three patients,
      two with diploid tumours and one with aneuploid tumour. Two patients with diploid
      tumours had metastatic disease 11-58 months after surgery. Only one patient with
      aneuploid tumour developed metastatic disease. There was no difference in local
      recurrence or metastases with the type of renal parenchymal-sparing surgery used
      (enucleation or partial nephrectomy) nor any significant difference in overall
      survival (P = 0.11). CONCLUSION: While DNA content might be of considerable
      predictive value for patients with RCC, these results showed that there was no
      difference in mortality rate, recurrence rate, or type of renal parenchymal
      sparing surgery used between aneuploid and diploid tumours.

PMID- 8535675
TI  - P53 and ploidy assessed by flow cytometry in bladder washings.
AB  - OBJECTIVE: To determine p53 expression in cells in bladder washings and to relate
      this to DNA content and clinical outcome. PATIENTS AND METHODS: Washings from 102
      patients (41 with newly diagnosed superficial tumours [pTa and pT1], 49 with
      recurrent superficial tumours and 12 with carcinoma invading bladder muscle) were
      studied. In 39 cases, the primary bladder tumour was also analysed. The rates of
      tumour recurrence and progression were determined for the new superficial tumours
      and related to both p53 expression and DNA content. RESULTS: Cells positive for
      p53 were detected in 22 of 90 (24%) washings from patients with superficial
      bladder cancer. P53 expression correlated with tumour stage (P < 0.05), grade (P
      < 0.05) and abnormal DNA content (P < 0.05). The analysis of pure urothelial
      (cyto-keratin-positive) cells improved the detection of DNA abnormalities (P <
      0.001). In 74% of cases where both washings and tumour were analysed, the results
      for DNA content agreed. Of 41 new superficial tumours, 27 (66%) recurred (11 were
      p53-positive, 16 were p53-negative, P = 0.221; 17 had abnormal DNA content, 10
      were diploid, P = 0.069). Four patients progressed (one was p53-positive, P =
      0.315 and all had abnormal DNA content, P = 0.072). CONCLUSION: P53-positive
      cells can be detected in washings using flow cytometry and were more commonly
      detected in association with aneuploid tumours. At short-term follow-up, flow
      cytometric analysis of DNA content in washings had greater predictive value than
      had p53 expression. Few washings contained aneuploid cells when the primary
      tumour contained diploid cells, although the collection of washings is a
      convenient way of sampling tumour cells.

PMID- 8535676
TI  - Serum granulocyte colony-stimulating factor levels in patients with urinary
      bladder tumour and various urological malignancies.
AB  - OBJECTIVES: To measure the serum levels of granulocyte colony-stimulating factor
      (G-CSF) in patients with urinary bladder tumour (UBT) or various urological
      malignant tumours, and to assess G-CSF production by tumour cells. PATIENTS AND
      METHODS: Peripheral blood was obtained, before operation or anti-cancer therapy,
      from 141 patients with UBT, 37 patients with other urological malignant tumours
      (21 with renal cell carcinoma, nine with renal pelvic or ureteric tumours, five
      with prostatic cancer, and two with testicular cancer), 38 patients with benign
      urological diseases (21 with benign prostatic hypertrophy, 11 with urolithiasis
      and six with a varicocele), and from 15 healthy donors. The serum G-CSF levels
      were quantified using an enzyme immunoassay. RESULTS: Of 141 patients with UBT,
      13 showed elevated serum G-CSF levels above the sensitivity of the assay (30
      pg/mL) with a mean value of 328 pg/mL. The serum levels in normal healthy donors
      and in patients with prostatic cancer, testicular cancer or varicocele were < 30
      pg/mL, while the levels were > 30 pg/mL in two of nine patients with renal pelvic
      or ureteric tumour (mean 754 pg/mL) and in one of 21 patients with renal cell
      carcinoma (40 pg/mL). The levels of serum G-CSF in several patients with benign
      prostatic hypertrophy or urolithiasis were also elevated, but the mean levels
      were low. The serum G-CSF levels in patients with UBT correlated with the
      increase of grade and the progression of the stage of UBT. Furthermore, patients
      with UBT and an undetectable level of serum G-CSF had higher disease-specific
      survival rates at the 5-year follow-up when compared with those with an elevated
      level of serum G-CSF. There was a positive correlation between serum G-CSF levels
      and white blood cell counts. T24 and J82 UBT cell lines and freshly separated
      tumour cells derived from the patient whose serum G-CSF level was high produced G
      CSF. CONCLUSION: These results suggest that elevated serum G-CSF level might be
      associated with a poor prognosis in patients with UBT and be due to the
      production of G-CSF by UBT cells.

PMID- 8535677
TI  - The burden of prostate cancer from diagnosis until death.
AB  - OBJECTIVE: To quantify the need for treatment and care in patients with
      conservatively treated prostate cancer. PATIENTS AND METHODS: All men who had
      been diagnosed with prostate cancer in a defined geographical area and who died
      within the period 1987-91 were identified. Patients treated with curative intent
      were excluded. Medical records from hospitals, nursing homes and community nurses
      for the period from diagnosis until death were scrutinized for the remaining 174
      patients. RESULTS: Of the 174 patients, 95% were symptomatic at diagnosis and 62%
      died from prostate cancer. All but two patients were hospitalized for prostate
      cancer, for a mean of 1 month. Thirty-six per cent needed regular nursing in
      nursing homes or by community nurses at home. Complications requiring
      hospitalization or long-term catheterization occurred in 49%. Prostatic surgery
      was performed in 66% and androgen ablation in 76% of the patients; palliative
      irradiation was given to 16% and 50% received analgesics regularly, including
      opiates or equivalents in 37%. Prednisone was given to 29%, after the failure of
      androgen ablation. CONCLUSION: Our findings demonstrate the considerable burden
      imposed both on patients and health-care resources by symptomatic prostate
      cancer, conservatively treated. There are few data available for comparison.

PMID- 8535678
TI  - Eliminating the need for per-operative frozen section analysis of pelvic lymph
      nodes during radical prostatectomy.
AB  - OBJECTIVE: To eliminate the need for per-operative frozen section analysis by
      using pre-operative serum prostate-specific antigen (PSA), clinical stage and
      Anderson biopsy grade to predict lymph node metastasis. PATIENTS AND METHODS:
      Between 1988 and 1994, 214 patients underwent bilateral pelvic lymphadenectomy
      before an intended retropubic radical prostatectomy for clinically confined
      prostate carcinoma. Preoperative serum PSA, clinical stage and Anderson biopsy
      grade were analysed to investigate whether they were able to predict the results
      of per-operative frozen sections of pelvic lymph nodes. RESULTS: Serum PSA level
      was the best predictor of a frozen section which was positive for lymph node
      metastasis, followed by biopsy grade. Clinical T-category combined with PSA level
      predicted lymph node status less well than did biopsy grade and had no additional
      value when combined with biopsy grade and PSA. Pre-operative serum PSA combined
      with biopsy grade predicted a negative frozen section result of bilateral pelvic
      lymphadenectomy with 95% certainty in at least 17% of patients undergoing radical
      prostatectomy for clinically confined prostate cancer. Frozen section analysis
      had a false negative rate of 4.7% when compared with histological staging.
      Therefore, combining those patients with an estimated 95% chance of a negative
      frozen section with the group of false negatives, 11 in 214 patients (5.1%) would
      have undergone radical prostatectomy while having micrometastases. CONCLUSIONS:
      Selecting men for whom the per-operative frozen section analysis could be omitted
      may save operating time and allow more efficient use of facilities.

PMID- 8535679
TI  - Is day-case prostatectomy feasible?
AB  - OBJECTIVE: To assess the possibility of discharging patients, catheter-free, on
      the same day that they undergo contact-laser prostatectomy. PATIENTS AND METHODS:
      Ten patients underwent contact vaporization of the prostate using the SLT
      (Surgical Laser Technologies, Oaks, PA, USA) Nd:YAG laser with an MTRL10 6 mm
      tip. Patients were selected in the out-patient clinic for day-case surgery on the
      basis of their good general health and clinically small glands. All patients had
      pre-operative urodynamic assessment and were proven obstructed and stable.
      Contact vaporization was carried out under general anaesthesia. Both intra
      operative blood loss and irrigant absorption were assessed. The follow-up at 3
      and 6 months included American Urological Association (AUA-7) symptom scores and
      the measurement of urinary flow rates. RESULTS: The mean operating time was 25.2
      min, with a mean application of 43.05 kJ of laser energy. The mean absorption of
      irrigant fluid was 30 mL and the mean intra-operative blood loss was 31 mL. Nine
      patients were discharged on the day of treatment. Two patients went into clot
      retention following discharge and had a suprapubic catheter sited, and two failed
      to void once discharged, necessitating catheterization for 2 weeks. At 3 and 6
      months, there was a substantial decrease in the AUA symptom score and an
      improvement in urinary flow rate. CONCLUSION: Day-case laser prostatectomy is
      possible, but the patients must be selected carefully and, perhaps more
      importantly, a specialist day-case anaesthetist must be available.

PMID- 8535680
TI  - Urodynamic assessment in the laser treatment of benign prostatic enlargement.
AB  - OBJECTIVE: To determine if bladder outlet obstruction can be adequately relieved
      after laser prostatectomy. PATIENTS AND METHODS: Since November 1992, a total of
      105 patients underwent laser treatment of the prostate because of complaints
      related to benign prostatic enlargement (BPE). To date, urodynamic data from a
      study of pressure flow analysis are available for 79 patients both at baseline
      and at 6 months after treatment. Patients were evaluated using changes in
      symptoms (IPSS symptom score), peak flow rate (Qmax), post-voiding residual
      volume (PVR), detrusor pressure at maximum flow (Pdet at Qmax), and the linear
      passive urethral resistance relation (LPURR). Moreover, patients with minimal
      bladder outlet obstruction were compared to patients with severe bladder outlet
      obstruction. RESULTS: There was a significant improvement in mean IPSS score from
      21.3 at baseline to 5.3 at the 6-month follow-up. The Qmax improved from 7.9 mL/s
      to 17.8 mL/s, and the PVR decreased from 91.6 mL to 15.6 mL. At baseline, > 80%
      of the patients were considered obstructed according to the analysis of pressure
      flow, whereas 6 months after laser treatment, only 5% of the patients were still
      considered obstructed. A comparison of the outcome between minimally obstructed
      patients and severely obstructed patients showed comparable improvements.
      CONCLUSION: Laser therapy of the prostate was, according to urodynamic
      parameters, capable of relieving outlet obstruction and minimally obstructed
      patients also showed a significant relief of outlet obstruction.

PMID- 8535681
TI  - Regression to the mean occurs in measuring peak urinary flow.
AB  - OBJECTIVE: To investigate the anomalous rises in maximum urinary flow rates seen
      in a prostate-diagnostic clinic. SUBJECTS AND METHODS: The study comprised 1994
      men aged 40-79 years registered at five health centres in Central Scotland,
      participating in a study of the natural history of benign prostatic hyperplasia
      (BPH), who completed a urodynamic assessment on up to three occasions: in the
      community, on referral to a prostate-diagnostic clinic and at a one-year follow
      up. RESULTS: Subjects referred to the diagnostic clinic on the basis of maximum
      flow rate (Qmax < 15 mL/s) and/or urinary symptomatology showed a mean increase
      in Qmax (P < 0.001) when tested at the clinic and at the one-year follow-up. In
      health centres which referred men to the clinic with no pre-selection, there were
      no significant changes in Qmax. CONCLUSION: Regression to the mean occurs when
      patients are selected on the basis of a low Qmax. The use of isolated low values
      of Qmax in the process of diagnosing BPH should be avoided.

PMID- 8535682
TI  - Transurethral microwave thermotherapy versus transurethral resection for
      symptomatic benign prostatic obstruction: a prospective randomized study with a 2
      year follow-up.
AB  - OBJECTIVE: To compare the outcome of transurethral resection of the prostate
      (TURP) and transurethral microwave thermotherapy (TUMT) on symptomatic benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with symptomatic BPH
      were treated by either TURP (32 patients; mean age 70 +/- 6 years) or TUMT (37
      patients; mean age 67 +/- 9 years) and assessed using the Madsen-Iversen symptom
      score, measurements of urinary free flow rate and post-void residual urine
      volume, digital rectal examination, transrectal ultrasonography, cystometry and
      pressure-flow measurement, ultrasonography or intravenous pyelography (IVP) of
      the upper urinary tract, urine analysis and routine blood chemistry including
      serum prostate-specific antigen (PSA) level. Examinations were repeated at fixed
      intervals for up to 24 months after treatment. RESULTS: After both TURP and TUMT
      there was an improvement in symptom score, residual urine volume, free flow rate
      and infravesical obstruction. The improvements of free flow rate and obstruction
      were more pronounced after TURP. Serious complications, such as bleeding
      requiring a re-operation, occurred only in patients who underwent TURP.
      CONCLUSION: Satisfactory results were obtained after both treatments and the
      improvements with either treatment lasted for at least 24 months.

PMID- 8535683
TI  - Transrectal and transurethral hyperthermia versus sham treatment in benign
      prostatic hyperplasia: a double-blind randomized multicentre clinical trial. The
      French BPH Hyperthermia.
AB  - OBJECTIVE: To compare the safety and efficacy of hyperthermia for the treatment
      of benign prostatic hyperplasia (BPH), by either the transrectal or transurethral
      approach, relative to sham treatment. PATIENTS AND METHODS: Two hundred patients
      from seven urological departments were randomized and treated in a single centre.
      Principal inclusion criteria were a peak flow rate (PFR) < 15 mL/s and residual
      urine < 300 mL/s. Comparisons were made between transurethral hyperthermia (TUH)
      and transurethral sham (TUS) and between transrectal hyperthermia (TRH) and
      transrectal sham (TRS) 12 months after treatment. Outcome was assessed by
      improvements in the Madsen score and PFR, and the incidence of side-effects.
      RESULTS: After 12 months, 145 patients were evaluated; 12 patients withdrew
      during treatment, 43 withdrew during follow-up and two were lost to follow-up.
      Withdrawals were mainly due to side-effects during treatment (17% in the TRH and
      1.5% in the TUH group) and to a lack of improvement during follow-up (14% in the
      TUH group, 19% in the TUS, 15% in the TRH and 10.5% in the TRS group received
      other treatments for BPH). Complications during treatment consisted mainly of
      local pain, urethral bleeding, urethral pain and acute retention, and were five
      times more frequent in the TRH than the TUH group (34% versus 6%). There was no
      improvement in PFR after TUH and TRH (response < 20%). Only TUH improved the
      Madsen score (TUH, +50% and TUS, +17%). CONCLUSION: Hyperthermia was not an
      effective treatment for BPH.

PMID- 8535684
TI  - The use of Doppler ultrasound in the clinical management of acute testicular
      pain.
AB  - OBJECTIVE: To evaluate the reliability and the clinical application of the use of
      a hand-held Doppler ultrasound flowmeter probe as an aid to differential
      diagnosis in the assessment of cases with acute testicular pain presenting to a
      district general hospital. PATIENTS AND METHODS: Over a period of 1 year,
      testicular Doppler ultrasonic assessment was performed on 56 patients admitted
      with acute scrotal pain. A hand-held Doppler ultrasound probe was used, with a
      transducer operating at 8 MHz. All the patients were assessed pre-operatively by
      a single operator in the Accident and Emergency department before transfer to
      theatre. The decision to explore the testis was made purely on clinical grounds
      by which ever emergency surgical team was on duty. The operating surgeons were
      not informed of the result of Doppler examinations before surgical exploration.
      RESULTS: Twenty-two patients were subsequently shown to have torsion of the
      testis at surgical exploration, all of whom had no Doppler signal over the
      affected side. Of the remaining 34 patients, who were subsequently shown not to
      have torsion at operation, normal testicular blood flow and cord-compression
      tests were demonstrated confidently in 33 patients when examined pre-operatively.
      Thus the sensitivity was 100% (22/22) and the specificity 97% (33/34).
      CONCLUSION: Testicular Doppler examination using an 8 MHz probe in conjunction
      with the cord-compression test is a useful, simple and highly accurate clinical
      tool which can differentiate between testicular torsion and other conditions
      presenting with acute testicular pain. It is also inexpensive and readily
      available in the district general hospital situation.

PMID- 8535685
TI  - The value of radionuclide scrotal imaging in the diagnosis of acute testicular
      torsion.
AB  - OBJECTIVE: To assess the accuracy of radionuclide scrotal imaging (RSI) in the
      diagnosis of testicular torsion and torsion of testicular appendages. PATIENTS
      AND METHODS: Eighty-seven patients (mean age 30.1 years, range 8-65) who
      presented with acute scrotal pain were evaluated by RSI and the results
      correlated with the clinical and surgical findings. RESULTS: Of the 87 patients,
      44 underwent scrotal exploration and 42 patients were treated conservatively. One
      patient with a 'missed torsion' pattern on RSI refused operation and was lost to
      follow-up. Of the 44 patients who underwent surgery, testicular torsion was found
      in 30 and torsion of testicular appendages in 14 patients. The specificity of the
      RSI in diagnosing testicular torsion was 100% and the sensitivity was 98%. An
      area of increased tracer activity in the presence of a normal radionuclide
      angiogram was suggestive of torsion of testicular appendages with a specificity
      of 93%. Of the 42 patients who were treated conservatively, 19 had epididymitis,
      according to clinical and RSI findings, 10 had torsion of testicular appendages,
      two had orchiepididymitis, two had hydrocele, two had haematocele and seven
      patients had normal testes. At a follow-up examination, normal testicles were
      found in all 42 patients. CONCLUSION: The RSI may assist in the evaluation of
      nontraumatic acute scrotum, and can clearly distinguish among testicular torsion,
      torsion of testicular appendages and epididymitis.

PMID- 8535687
TI  - Laparoscopic varicocelectomy: indication, technique and surgical results.
AB  - OBJECTIVE: To assess the efficacy of laparoscopic techniques for the operative
      therapy of varicocele. PATIENTS AND METHODS: Fifty-one patients who underwent
      laparoscopic varicocelectomy due to subfertility and/or pain between June 1992
      and December 1994 were evaluated. RESULTS: In all patients, except one with a
      remaining slight reflux on post-operative Valsalva's manoeuvre, operative therapy
      was effective and no major complications occurred. The procedure was minimally
      invasive, effective and, because the anatomy was readily seen, multiple veins
      and/or collaterals were easily assessed and the surgery precise. CONCLUSION: The
      laparoscopic technique is an efficient, minimally invasive operation with optimal
      results. After a brief period of training the operation can be performed in 15-30
      min and is therefore no longer than embolization techniques. Treatment of both
      sides in one session was not a problem.

PMID- 8535686
TI  - Evaluation of testicular volume by three orchidometers compared with
      ultrasonographic measurements.
AB  - OBJECTIVE: To investigate the accuracy of three commonly used orchidometers
      (Prader, Takihara punched-ring and Seager) compared with ultrasonography (US) for
      the measurement of testicular size. SUBJECTS AND METHODS: A prospective,
      randomized, blinded trial to compare three methods of measuring testicular volume
      was performed, involving 31 men attending the Fertility Problems Clinic for the
      assessment of fertility. Testicular size was measured independently by three
      doctors and compared with estimates obtained independently by US in the Radiology
      department. RESULTS: The Prader and Takihara punched-ring orchidometers
      consistently overestimated testicular size compared with that estimated by US. A
      substantial proportion of the measurements obtained using the Prader orchidometer
      were more than twice the value estimated by US. CONCLUSIONS: The Prader and
      Takihara orchidometers were useful in comparing different testicular sizes but
      the absolute values obtained would probably be overestimated in many clinical
      situations. The Seager orchidometer, although more difficult to use, agreed best
      with the US estimates.

PMID- 8535688
TI  - The management of urological malignancies during pregnancy.
AB  - Urological malignancies occur only rarely during pregnancy. However, when they do
      occur, the urologist must use judgement to deliver optimal care to the mother
      without unnecessary jeopardy to the fetus. Radiation exposure should be avoided
      if possible and therapy should be determined by the nature of the tumour and the
      stage of pregnancy.

PMID- 8535689
TI  - Non-traumatic rupture of the urinary tract during pregnancy.
AB  - OBJECTIVE: To review published cases of rupture of the urinary tract during
      pregnancy and illustrate the clinical manifestations of this serious complication
      of pregnancy. METHODS: Reported cases of urinary tract rupture were reviewed and
      a new case described. RESULTS: Spontaneous rupture of the urinary tract during
      pregnancy is rare; a review of the literature revealed only 24 cases, most
      commonly occurring in diseased kidneys. In the majority of cases the rupture was
      associated with underlying diseases of the kidney, the most common being renal
      tumours. Of the 25 cases examined, 12 had ruptures of the collecting system and
      13 had ruptures of the renal parenchyma: 21 were diagnosed during pregnancy in
      the second and third trimester and four within the first 24 h postpartum.
      CONCLUSION: Pregnancy-induced changes in the urinary tract exaggerate any
      weakness of the parenchyma or collecting system. Pregnant patients with
      overdistension of the upper urinary tract should undergo routine ultrasonography
      and be observed carefully for infection or haematuria.

PMID- 8535690
TI  - Fetal pelvi-ureteric junction obstruction: predictors of outcome.
AB  - OBJECTIVE: To examine the relationship between pre-natal ultrasonographic
      findings typical of pelvi-ureteric junction (PUJ) obstruction and post-natal
      renal function in the affected kidney. PATIENTS AND METHODS: This retrospective
      study comprised 35 infants in whom pre-natal ultrasonography had identified a
      unilateral pattern of dilatation of the renal pelvis and calices typical of PUJ
      obstruction. In each case, the presence of unilateral hydronephrosis had been
      confirmed post-natally by ultrasonography, and differential function and drainage
      evaluated by isotope renography. The results of isotope renography were compared
      with the severity and timing of onset of the fetal hydronephrosis. RESULTS:
      Eleven kidneys (31%) appeared normal in the second trimester and dilatation only
      became apparent during the third trimester. Mean differential function in these
      kidneys was 48%. However, mean differential function was reduced (mean 38%) in
      those kidneys noted to be dilated between 16 and 24 weeks gestation. Differential
      function was loosely correlated with the severity of dilatation in early onset
      cases, i.e. the mean differential function was 42% for mild, 37% for moderate and
      27% for severe dilatation. A considerable variation in differential function
      values was present in each group except for those with severe dilatation, which
      was a significant predictor of poor functional outcome when compared with mild
      and moderate dilatation combined (P < 0.01). CONCLUSION: Fetal PUJ obstruction is
      a heterogeneous condition permitting only broad predictions of functional
      outcome. Severe dilatation detected on second trimester imaging predicted
      significant loss of function. Mild and moderate degrees of dilatation were
      associated with a one in three risk of functional impairment in the obstructed
      kidney.

PMID- 8535691
TI  - EMLA cream anaesthesia for frenuloplasty.
AB  - OBJECTIVE: To evaluate the use of a eutectic mixture of local anaesthetics (EMLA)
      cream as the sole anaesthetic for frenuloplasty. PATIENTS AND METHODS: Fifteen
      patients (mean age 25.6 years, range 19-41) were given topical EMLA cream 30 min
      before frenuloplasty; a Tegaderm dressing was applied to keep the anaesthetic in
      place. The level of anaesthesia was assessed on arrival in theatre using pin
      prick testing and the patients were asked to grade their level of pain during the
      procedure using a visual analogue scale. If the level of anaesthesia was
      inadequate for the operation to be performed, then supplementary infiltrative
      anaesthesia was administered. RESULTS: Fourteen patients had pain scores of zero
      and were fully anaesthetized during the procedure. One patient's Tegaderm
      dressing was displaced soon after application and he was inadequately
      anaesthetized on testing, had a pain score of 4 and required infiltrative
      lignocaine before proceeding with frenuloplasty. CONCLUSIONS: EMLA cream is a
      well-tolerated and reliable anaesthetic for frenuloplasty. Using a condom to keep
      the cream in place would reduce the small failure rate associated with the
      displacement of the Tegaderm dressing.

PMID- 8535692
TI  - A technique for removal of the Urolume endourethral wallstent prosthesis.

PMID- 8535693
TI  - A method to avoid bursting the blocked catheter balloon in the female patient.

PMID- 8535694
TI  - Bladder stone formation on a swallowed knife blade and spontaneous passage
      through a vesicovaginal fistula.

PMID- 8535695
TI  - Sternal dehiscence secondary to prostatic carcinoma.

PMID- 8535696
TI  - Giant bladder stone in a child.

PMID- 8535697
TI  - Duplication of multiple systems and organs.

PMID- 8535698
TI  - Obstructive anuria following fulguration of posterior urethral valves and Foley
      catheter drainage of the bladder.

PMID- 8535699
TI  - Adult Wilms' tumour presenting as polycythaemia.

PMID- 8535700
TI  - Acute urinary retention in the young female.

PMID- 8535701
TI  - Fournier's gangrene following delayed rupture of an ileal neobladder (Hautmann).

PMID- 8535702
TI  - Psychogenic urinary retention in a male.

PMID- 8535703
TI  - Renal cell carcinoma as a source of recurrent urinary tract infections.

PMID- 8535704
TI  - Broadening the concept of urinary tract infection.

PMID- 8535705
TI  - Urological day case surgery.

PMID- 8535706
TI  - Urological day case surgery.

PMID- 8535707
TI  - Angiogenesis in urological malignancy.

PMID- 8535708
TI  - Establishing a new department of urology: an integrated system for national
      health service and private care.

PMID- 8535709
TI  - Objective evaluation of the outcome of endopyelotomy using Whitaker's test and
      diuretic renography.
AB  - OBJECTIVES: To assess the role of Whitaker's test (WT) and 99mTc-diethylene
      triamine penta-acetic acid diuretic renography (DRG) in determining objectively
      the outcome of endopyelotomy, and to rationalize the frequency and timing of such
      evaluation after endopyelotomy. PATIENTS AND METHODS: Thirty-one patients (age >
      15 years) were prospectively evaluated after percutaneous endopyelotomy. WT was
      performed at 4-6 weeks via the nephrostomy maintained for external drainage, 24 h
      after removing the splint. DRG was performed at 3, 6 and 12 months, and then
      annually. RESULTS: WT performed 24 h after removing the splint diagnosed pelvic
      pressures in the unobstructed range (< 15 cmH2O) in 21 of the 24 patients were
      also evaluated with DRG at 3 months. An intra-pelvic pressure of > 15 cmH2O was
      correlated with a pattern of obstruction on DRG in all three units. Despite an
      unobstructed WT in 18 patients, categorization of DRG drainage showed disparity
      in six cases. All six renal units had a large pelvic area (> 15.0 cm2 in two and
      > 20.0 cm2 in four) and/or a poor renal function (separate glomerular filtration
      rate [GFR] of < or = 25 ml/min in four of the six units). The drainage pattern on
      DRG was unevaluable in two renal units as the function was poor (separate GFR <
      15 ml/min). During the first year, the drainage pattern on DRG improved in four
      cases. When followed beyond one year, the drainage pattern deteriorated at 2
      years in only one of 14 evaluated renal units with an initial unobstructed WT.
      CONCLUSION: Using objective methods of evaluation, endopyelotomy was successful
      in relieving obstruction in 87% of cases. If inaccuracies in the interpretation
      of DRG, i.e. a large pelvic capacity and poor renal function, are accounted for,
      the results of WT as early as 24 h after removal of the splint correlated with
      DRG. Drainage patterns on DRG did not deteriorate during the first year. An early
      post-operative evaluation with WT or DRG, as appropriate, is thus sufficient
      evidence of the success of the procedure. Evaluations repeated during the first
      year after endopyelotomy may be unnecessary.

PMID- 8535710
TI  - Effect of dietary intake on urinary oxalate excretion in calcium renal stone
      formers.
AB  - OBJECTIVE: To investigate the influence of dietary intake on urinary oxalate
      excretion in calcium renal-stone formers. PATIENTS AND METHODS: Dietary intake
      was monitored by using the dietary-record method in 60 idiopathic stone formers.
      The patients collected their urine for 24 h at home and their urinary oxalate
      excretion rate was determined. The relationship between the daily intake of
      various nutrients and urinary oxalate excretion was examined by both monovariate
      and multivariate analyses. RESULTS: By monovariate analysis, the intake of
      carbohydrate, total protein and fat were significantly correlated with urinary
      oxalate excretion, but the intake of calcium and body surface area were not. In
      addition, the intake of total protein was highly correlated with that of fat. By
      multivariate analysis, the intake of carbohydrate and fat were significantly
      related to urinary oxalate excretion, and the intake of calcium was inversely
      correlated with urinary oxalate excretion, but the intake of total protein showed
      no significant correlation. CONCLUSION: The intake of carbohydrate and fat was
      positively and the intake of calcium was inversely correlated with urinary
      oxalate excretion in stone formers and, taken together, these findings suggested
      that fat plays an important role in urinary oxalate excretion and that protein
      has a minimal effect.

PMID- 8535711
TI  - A controlled study of intravesical epirubicin with or without alpha 2b-interferon
      as prophylaxis for recurrent superficial transitional cell carcinoma of the
      bladder. Finnish Multicentre Study Group.
AB  - OBJECTIVES: To evaluate the efficacy of intravesical epirubicin with or without
      alpha 2b-interferon (alpha 2b-IFN) as a prophylactic treatment for recurrent
      superficial transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS
      AND METHODS: A total of 81 patients with superficial (stage Ta and T1), well or
      moderately differentiated (grades 1 and 2) TCC were treated between June 1988 and
      December 1993. The patients were randomized into three groups: Group 1 was
      treated by transurethral resection (TUR) alone; Group 2 received 50 mg epirubicin
      and Group 3 received 50 mg epirubicin combined with 10 MU alpha 2b-IFN,
      intravesically in 50 mL sterile buffer solution. The instillations were started 1
      week after TUR and were performed weekly during the first month and then once a
      month for one year. The patients were followed for a total of 2 years. Recurrence
      rate and tumour rate were calculated to assess the behaviour of the disease.
      RESULTS: The patients were followed for a mean of 20 months. Patients receiving
      intravesical chemoimmunotherapy (Group 3) had the most favourable outcome; they
      had comparatively lower recurrence and tumour rates, fewer patients with
      recurrences and, most importantly, the longest disease-free interval. Side
      effects were mostly mild and transient, and no differences were found among the
      groups. CONCLUSIONS: In reducing the number of patients having recurrences and
      extending the recurrence-free interval, intravesical chemoimmunotherapy with
      epirubicin and alpha 2b-IFN had a promising effect on the natural course of
      superficial bladder cancer, particularly in patients with a history of prior
      recurrences.

PMID- 8535712
TI  - Immunohistological findings in patients with superficial bladder carcinoma after
      intravesical instillation of keyhole limpet haemocyanin.
AB  - OBJECTIVE: To determine whether keyhole limpet haemocyanin (KLH) instilled
      intravesically improves the local cellular response within the bladder wall of
      patients suffering from superficial bladder carcinoma. PATIENTS AND METHODS:
      Twelve patients (10 men and two women, mean age 67 years, range 42-85) with
      superficial carcinomas of the bladder were treated for 6 consecutive weeks and
      then monthly for 1 year with 20 mg KLH in 20 mL saline instilled intravesically
      after complete resection of the tumours. Biopsies were taken for
      immunohistochemical examination before treatment and again 6 weeks, 3, 6 and 9
      months after treatment. Six patients with no evidence of cystitis or malignant
      bladder disease acted as a control group. Immunofluorescent staining of the
      biopsies was performed using monoclonal antibodies to the T-cell markers CD4 and
      CD8, and to CD14 (monocytes), CDw15 (granulocytes), CD19 B-cells (Pan-B), CD68
      (macrophages) and HLA-DR. Anti-KLH antibody-producing plasma cells were detected
      using a standard technique. A semiquantitative analysis of locally infiltrating
      cell types was performed. RESULTS: After treatment with KLH the increase of CD8+
      suppressor cells was less pronounced than that of CD4+ helper cells. The T
      helper/inducer to T-suppressor/cytotoxic cell ratio thus altered from 0.8:2.0
      before treatment to 1.6:2.3 afterwards. Hence, the number of T-helper cells had
      increased considerably, whereas there was only a moderate increase in the number
      of T-suppressor cells. This cellular ratio could be detected for 9 months after
      KLH therapy. The numbers of activated HLA-DR+ immune cells in the submucosa and
      among urothelial cells also increased after KLH instillation. The degree of
      mononuclear cell infiltration of the submucosa increased considerably, but
      granulocyte infiltration was only moderate. Lymph follicles with enhanced B
      lymphocyte counts were also detected. CONCLUSION: Immune-cell infiltration into
      the urothelium and enhanced activation (expression of class II antigens) suggests
      distinct processes of cellular antigen recognition, which could be detected for
      up to 9 months after the beginning of KLH therapy. This may represent a basic
      functional mechanism of KLH therapy.

PMID- 8535713
TI  - Immunohistochemical analysis of nm23 protein in transitional cell carcinoma of
      the bladder.
AB  - OBJECTIVES: To elucidate the clinical significance of the nm23 gene product in
      transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: The
      immunoreactivity of nm23 protein and proliferating cell nuclear antigen (PCNA)
      were evaluated in paraffin-embedded tumour samples obtained from 74 patients with
      TCC of the bladder who underwent total cystectomy between 1981 and 1993 and
      compared with the histological findings and clinical outcome. RESULTS: The
      immunoreactivity of nm23 protein was positive near basement membrane in normal
      transitional epithelium and superficial TCCs; it could also be positive at the
      invasive front of TCCs. The immunoreactivity of nm23 protein in TCCs was
      significantly higher than that in normal transitional epithelium and correlated
      significantly with the expression of PCNA and with histological grade. Similarly,
      immunoreactivity was significantly higher in invasive TCCs than in superficial
      TCCs; however, there was no significant difference between superficial TCCs and
      normal transitional epithelium. Immunoreactivity of nm23 protein was not
      associated with the early development of metastasis after radical surgery or with
      a favorable clinical outcome. CONCLUSION: Immunoreactivity of nm23 protein
      appeared to be associated with the proliferation and progression of TCC of the
      bladder. The potential role of nm23 as a suppressor of the metastatic activity of
      tumours was less prominent, partly because of mutations of nm23 in TCCs of the
      bladder.

PMID- 8535714
TI  - Determinants of treatment-seeking behaviour for urinary symptoms in older men.
AB  - OBJECTIVE: To determine the factors associated with seeking treatment for urinary
      symptoms among older men in a European population. SUBJECTS AND METHODS: A
      community survey involving a representative nationwide sample of 2011 French men
      aged between 50 and 80 years was performed and information collected using an
      interviewer-administered questionnaire. RESULTS: Visiting a doctor for urinary
      symptoms was associated with the perceived bothersomeness of urinary symptoms, in
      addition to and independently of the level of symptom severity. It was also
      associated with higher socio-economic class. Many partners of men with urinary
      symptoms were unaware of their condition. CONCLUSIONS: This study emphasizes the
      importance of including the perception of bother associated with urinary symptoms
      in addition to urinary severity and provides information useful for inclusion in
      education programmes on urinary symptoms.

PMID- 8535715
TI  - Development of nerves containing nitric oxide synthase in the human male
      urogenital organs.
AB  - OBJECTIVE: To determine the spatial and temporal distribution of nitric oxide
      synthase (NOS) in the urogenital organs of a series of human male fetuses, using
      an immunohistochemical technique. MATERIAL AND METHODS: Thirteen pre-natal
      specimens ranging in gestational age from 13 to 30 weeks were acquired following
      abortion or miscarriage. The distribution of NOS, which catalyses the production
      of nitric oxide (NO), was revealed using an indirect immunolabelling technique
      and compared with the overall innervation of each specimen visualized using the
      general nerve-marker protein gene product 9.5 (PGP). RESULTS: At 13 weeks of
      gestation the majority of nerves supplying the developing prostate gland
      expressed NOS while similar nerves formed a very minor proportion of the total
      innervation to the urinary bladder and intramural ureters. With increasing
      gestational age, NOS-containing nerves became more numerous in the lower urinary
      tract, the majority occurring at the bladder neck and around the prostatic
      urethra. In contrast, NOS-containing nerves were not detected in the muscle coat
      of the vas deferens and seminal vesicle until 23 weeks of gestation and at 30
      weeks still only formed a small proportion of the intramuscular nerves. From 23
      weeks onwards NOS-containing nerves were present occasionally in the dense
      subepithelial nerve plexuses which developed in the bladder, prostate, vas
      deferens and seminal vesicle. Also from 23 weeks onwards, many of the epithelial
      cells lining the vas deferens, seminal vesicle and ejaculatory ducts showed
      immunoreactivity to NOS but no immunoreactivity was observed in the epithelial
      lining of the urinary bladder and the intramural ureters. CONCLUSION: Based on
      the comparative density of NOS-containing nerves and the difference in their
      temporal development among the various urogenital organs it is apparent that NO
      plays an increasingly important role in the autonomic control of the lower
      urinary tract during fetal development but that its involvement in the functional
      control of the vas deferens and seminal vesicle is relatively minor before birth.

PMID- 8535716
TI  - Comparison of relaxation responses of detrusor strips from neuropathic and
      control patients.
AB  - OBJECTIVES: To confirm the existence of relaxation responses to electrical-field
      stimulation in strips of human detrusor, and to compare these responses in strips
      from control subjects with those in strips from a group of neuropathic patients
      exhibiting hyperreflexia. PATIENTS AND METHODS: Detrusor specimens were obtained
      at operation from a group of control patients, and from a group of patients with
      neuropathy (mainly spina bifida) and a history of hyper-reflexia. Muscle strips
      were prepared from these, mounted in organ baths, and contracted by exposure to a
      modified Krebs' solution containing 26 mM KCl and atropine. Relaxation responses
      were induced by an electrical-field stimulation (50 V, 90 microsecond pulses at 2
      16 Hz for 10 s). RESULTS: Of 29 strips, 20 (69%) from control patients showed
      relaxations, compared with 17 of 28 strips (61%) from neuropathic patients (P >
      0.1). The maximum relaxation response in the control strips was 49 +/- 5.6% (mean
      +/- SEM) of the maximum relaxation induced by isobutyl methylxanthine, compared
      with 43 +/- 4.8% in the strips from neuropathic patients (P > 0.1). The maximum
      response occurred at similar frequencies (4 or 8 Hz) in the two groups. The
      relaxations were reduced by the inhibitor of nitric oxide synthase, N-nitro L
      arginine methyl ester (0.1 mM, P < 0.05), but were not affected by guanethidine
      (50 microM) or tetrodotoxin (0.5 microM). CONCLUSION: These results confirm the
      existence of field stimulation-induced relaxation in human detrusor, but suggest
      that hyper-reflexia in the neuropathic bladder cannot be accounted for by any
      deficiency in this response.

PMID- 8535717
TI  - Regional variations in the neural control of the female pig urethra.
AB  - OBJECTIVE: To establish the regional variation, if any, in the distribution of
      sympathetic and parasympathetic nerves within the urethra of the female pig and
      to correlate this with regional variations in the response of the smooth muscle
      to sympathetic and parasympathetic nerve stimulation and the application of
      phenylephrine and carbachol. MATERIALS AND METHODS: Female pig urethras were
      obtained from a local abattoir. Serial sections were cut from the proximal,
      middle and distal regions of the urethra and stained using tyrosine hydroxylase
      immunohistochemistry and acetylcholinesterase histochemistry for the
      demonstration of sympathetic and parasympathetic nerves, respectively. Strips of
      smooth muscle dissected from the same regions of the urethra were also mounted in
      organ baths to record isometric tension. Responses to nerve stimulation and alpha
      adrenoceptor and muscarinic receptor activation were recorded. RESULTS: Tyrosine
      hydroxylase- and acetylcholinesterase-positive staining was demonstrated
      throughout the urethra. However, the density of sympathetic innervation was
      greatest in those strips dissected from the distal urethra, whilst the
      parasympathetic innervation was uniform throughout the length. Strips of urethral
      smooth muscle mounted for tension recording generated spontaneous tone. Smooth
      muscle dissected from the proximal urethra developed the greatest tone, whilst
      strips from the distal urethra generated significantly less. Responses to nerve
      stimulation were complex; sympathetic nerve stimulation elicited frequency
      dependent contraction in all strips, but the response was most pronounced in the
      distal strips where tone was low. Conversely, parasympathetic nerve stimulation
      elicited the greatest contractile response from the proximal urethral strips. In
      all strips, but in particular those dissected from the proximal urethra, the
      contractile responses were attenuated by the occurrence of a non-adrenergic, non
      cholinergic (NANC), non-nitrergic relaxation as stimulation frequency was
      increased. Phenylephrine and carbachol also produced concentration-dependent
      contraction of all urethral strips. Like the nerve-mediated responses,
      contraction in response to phenylephrine was most pronounced in the distal
      urethral strips whilst the response to carbachol was most pronounced in the
      proximal urethral strips. CONCLUSIONS: The results demonstrated a regional
      variation in the distribution of sympathetic nerves within the urethra of the
      female pig which would appear to be mirrored not only in the responsiveness of
      the tissue to sympathetic nerve stimulation but also in its response to alpha
      adrenoceptor stimulation. In contrast, although no regional variation in the
      distribution of parasympathetic nerves could be demonstrated histologically,
      responses to nerve stimulation and the muscarinic agonist carbachol were most
      pronounced in the proximal urethral strips.

PMID- 8535718
TI  - Urethral sphincter volumes in women with obstructed voiding and abnormal
      sphincter electromyographic activity.
AB  - OBJECTIVE: To investigate the role of transrectal ultrasonography (TRUS) of the
      female urethral sphincter and to compare sphincter volumes in controls and women
      with obstructed voiding associated with abnormal myotonic-like electromyographic
      (EMG) activity in the urethral sphincter. PATIENTS AND METHODS: Fourteen women
      patients (mean age 29 +/- 3.2 years) with symptoms of urinary outlet obstruction
      underwent videocystometrography (VCMG), urethral sphincter EMG and TRUS. Their
      sphincter volumes were compared with those obtained from 20 age-matched control
      patients with other urodynamic diagnoses or normal urodynamics. RESULTS: In every
      patient the urethral sphincter was identified as an ovoid, hypoechoic structure
      distal to the bladder outlet. The mean volume of the sphincter in those patients
      with abnormal EMG activity (3.05 +/- 0.23 cm3) was significantly greater than
      that in the control group (1.30 +/- 0.09 cm3; P < 0.001). CONCLUSION: TRUS
      provided a useful method of imaging the urethral sphincter in women. The results
      suggest that there was an increase in the volume of the urethral sphincter in
      females with obstructed voiding, providing collateral evidence that the abnormal
      EMG activity is a significant factor in the pathophysiology of the disorder.

PMID- 8535719
TI  - Tethered spinal cord: the effect of neurosurgery on the lower urinary tract and
      male sexual function.
AB  - OBJECTIVE: To determine the effect of neurosurgical untethering on the lower
      urinary tract and male sexual function, in patients with tethered spinal cord.
      PATIENTS AND METHODS: Thirty-six children with tethered spinal cord due to
      neurospinal dysraphism were assessed clinically and urodynamically before and
      after surgical untethering. Sexual function was evaluated in 14 boys before and
      after neurosurgery. In young boys, the assessment was by parental observation and
      was considered normal if erections had been observed regularly, or if the child
      had mentioned having an erection at any time. Older patients were asked if they
      had achieved voluntary erections and whether or not they were able to ejaculate.
      RESULTS: The mean follow-up was 91 months and the mean follow-up after
      neurosurgery was 34 months. A lasting improvement of urinary tract function
      occurred in only one patient, while another became worse. Seven children had
      temporary changes of bladder/sphincter function; two developed detrusor
      overactivity with sphincter dyssynergia and five had signs of bladder
      denervation. Long-term follow-up showed no permanent changes of lower urinary
      tract function in 94% of 34 patients. Sexual function was considered normal in 13
      boys. One boy apparently gradually lost erectile ability before untethering and
      regained it after surgery, while another boy had erectile dysfunction post
      operatively for almost 6 months. CONCLUSION: Changes in bladder-sphincter
      function after untethering are usually transient and often the result of partial
      denervation. Although a small group of children seem to benefit from untethering,
      others can become worse and the individual outcome cannot be predicted. Erectile
      dysfunction can occur and parents and patients have to be informed of this
      possible complication. As pre-operative progression of neurological symptoms and
      post-operative denervation were observed only in patients with myelomeningocele
      and lipomyelomeningocele, this group may be distinct from patients with occult
      forms of spinal dysraphism. The natural history in the latter group of patients
      is unclear and a beneficial effect of prophylactic untethering remains to be
      proven by controlled prospective studies.

PMID- 8535720
TI  - Bladder and erectile dysfunction before and after rectal surgery for cancer.
AB  - OBJECTIVE: To establish the incidence of bladder and erectile dysfunction after
      rectal surgery for cancer. PATIENTS AND METHODS: Twenty patients (16 men and four
      women, median age 66 years, range 36-78) with carcinoma of the rectum were
      prospectively studied immediately before and 4 months after operation by clinical
      assessment, uroflowmetry and video-cystometrography. All patients were
      catheterized routinely at the time of surgery. Those experiencing voiding
      difficulties after catheter removal were managed by intermittent self
      catheterization or an indwelling urethral catheter. RESULTS: Before surgery, only
      six patients had completely normal bladder function and 13 of the 16 men were at
      least partially potent. Eight of the 19 patients who eventually had surgery
      developed identifiable bladder dysfunction, of whom three had urodynamic evidence
      of complete bladder denervation. Three men who were potent before became impotent
      after surgery. CONCLUSIONS: Bladder and erectile dysfunction are recognized
      complications of radical rectal surgery, although there is significant variation
      in the reported risk; much of this variability is related to the retrospective
      nature of most previous studies. This study demonstrates the importance of
      prospective urodynamic evaluation and confirms that the small but significant
      risk of permanent bladder dysfunction is likely to be related to pelvic nerve
      injury at the time of surgery.

PMID- 8535721
TI  - Treating erectile dysfunction with a vacuum tumescence device: a retrospective
      analysis of acceptance and satisfaction.
AB  - OBJECTIVES: To evaluate the quality of erections, ability to perform sexual
      intercourse, incidence of complications and satisfaction of patients using an
      external vacuum erection device in the treatment of erectile failure. PATIENTS
      AND METHODS: Of the 61 impotent men who participated in this clinical trial, 49
      used the device and were surveyed. The mean follow-up period was 12.8 months. A
      subjective rating scale from 1 to 10 was used to assess the patients'
      satisfaction with the device, where 1 indicated 'dissatisfied' and 10 indicated
      'very satisfied'. RESULTS: The ease of using the device, satisfaction with the
      quality of erections and ability to perform intercourse were given scores > 5 by
      88, 84 and 82% of the patients, respectively. Sixteen (33%) of the men withdrew
      from the trial, primarily because they were unable to achieve and maintain a full
      erection, or suffered conflicts in their relationship, or for reasons not related
      to the device. Overall, the effectiveness rate was 67%. Of 32 patients with
      arteriogenic impotence, 28 (88%) had satisfactory results and had an improvement
      in their capacity for spontaneous erections with the device. The most frequent
      adverse effects were blocked ejaculation, bruising or the development of
      ecchymosis, discomfort during pumping and discomfort from using the constriction
      bands. CONCLUSION: These results suggest that the vacuum device is an effective
      and safe treatment for impotence of various aetiologies, especially for those
      patients with arteriogenic impotence.

PMID- 8535722
TI  - Treatment of urethral stones by retrograde manipulation and extracorporeal shock
      wave lithotripsy.
AB  - OBJECTIVE: To assess the effect of retrograde manipulation and extracorporeal
      shock wave lithotripsy (ESWL) as a monotherapy for urethral stones that are not
      associated with urethral strictures. PATIENTS AND METHODS: Between August 1993
      and January 1995, 34 male patients (mean age 38.7 years, range 7-55) presented
      with urethral stones. No patient had a suggested or past history of urethral
      stricture. Lidocaine jelly (2%) was instilled and retained inside the urethra for
      5 min. A 16 F urethral catheter was advanced gently to push the stone back to the
      urinary bladder. Twenty patients had ESWL of their stones in the bladder, using a
      Storz Modulith SL20, in the prone position. Tilting the patient about 15 degrees
      towards the side with the stone minimized movement of the stone during
      fragmentation. In-line co-axial echography (3.5 MHz) and intermittent pulsed
      fluoroscopy were used to monitor stone fragmentation. In situ fragmentation of
      posterior urethral stones was not possible because localization was difficult and
      the treatment was painful. Thirteen patients had cysto-urethroscopy and
      mechanical cystolitholapaxy under general anaesthesia. RESULTS: Stones impacted
      in the posterior urethra in 31 (91%) patients and in the anterior urethra in
      three (9%) patients. Stones ranged in size from 7 to 25 mm. One patient expelled
      an anterior urethral stone after the instillation of 2% lidocaine jelly. The
      urethral stones were pushed back to the bladder without complication in the
      remaining 33 patients. All 20 patients except one had their stones fragmented by
      ESWL in one session. The mean number of shock waves was 3600 +/- 1480 (range 1200
      6000) and the generator voltage ranged between 5 kV (560 bar) to 8 kV (940 bar).
      No patient in the ESWL group required anaesthesia or analgesia. Thirteen patients
      had successful mechanical cystolitholapaxy with no complications. CONCLUSION:
      Both endoscopic lithotripsy and ESWL of urethral stones are safe and effective.
      However, transurethral lithotripsy requires general anaesthesia and carries a
      risk of bladder and urethral trauma. This study demonstrated that, in the absence
      of urethral stricture, urethral stones can be pushed back safely to the urinary
      bladder and fragmented effectively by ESWL. The success of the treatment depends
      on adequate anaesthesia of the urethra before inserting the urethral catheter. We
      propose that this new technique should be considered before resorting to
      endoscopic or surgical management of urethral stones, particularly in children.

PMID- 8535723
TI  - Simplified sperm retrieval and intracytoplasmic sperm injection in patients with
      azoospermia.
AB  - OBJECTIVE: To evaluate the rate of recovery of spermatozoa from the epididymis
      using a percutaneous aspiration technique and to assess the fertilization rate
      following intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS: Forty
      two patients with azoospermia underwent a total of 46 treatment cycles of in
      vitro fertilization (IVF) and ICSI. The sperm used for ICSI was retrieved
      percutaneously by fine-needle aspiration and syringe suction (percutaneous
      epididymal sperm aspiration, PESA) from the epididymis in 28 patients (mean age
      34.9 years), over 32 cycles. Six patients underwent microsurgical sperm
      aspiration (MESA) and in the remaining eight patients, neither percutaneous
      aspiration nor MESA yielded suitable sperm and spermatozoa extracted from
      testicular biopsy were used. RESULTS: A total of 362 oocytes were collected and
      of those, 286 (79%) were subjected to ICSI. Of the injected oocytes, 49 (17.2%)
      were damaged, 138 (48.3%) achieved normal fertilization and, of those, 112
      (81.2%) cleaved. A total of 67 embryos were transferred and 18 more were suitable
      for cryopreservation. Of the 25 cycles with embryo transfer, eight resulted in a
      pregnancy and of these, one miscarried. The pregnancy rate was 25% per cycle and
      32% per embryo transfer. The implantation rate was 12%. CONCLUSIONS: This
      extensive series of PESA/ICSI cycles indicates that PESA can be used successfully
      to retrieve spermatozoa in patients with azoospermia. The technique is simple,
      cost-effective and is associated with fewer complications compared to an open
      microsurgical procedure.

PMID- 8535724
TI  - Measuring the fetal kidney with ultrasonography.
AB  - OBJECTIVES: To establish a normal range of measurements for the external and
      internal dimensions of the fetal kidney and, if possible, to correlate these
      measurements with gestational age. SUBJECTS AND METHODS: The external and
      internal dimensions of the fetal kidney were measured in 810 women selected on
      the grounds of obstetric, fetal or technical risk factors from a consecutive
      series of 1136 women attending the ante-natal ultrasonography clinic of a
      district general hospital. Post-natal data were obtained from medical records on
      1122 newborns. The maximum of pairs of renal measurements was used for analysis.
      Measurements were cross-sectional in 347 cases and longitudinal in 463. The total
      number of measurement episodes was 2294. RESULTS: External renal dimension and
      gestational age were closely related, enabling accurate growth centile charts to
      be constructed. The correlation between renal pelvic dimension and gestational
      age was weak. The maximum dimension of the renal pelvis at any gestational age in
      92.7% of fetuses was < 5 mm. Using longitudinal measurements, 6.5% of cases with
      a renal pelvic dimension of < 5 mm at the first scan measured > or = 5 mm at a
      subsequent scan, but 53.3% with a dimension of > or = 5 mm at the first scan also
      measured > or = 5 mm at the subsequent scan. CONCLUSION: It is possible to assess
      the growth and size of the fetal kidney according to gestational age but this
      does not apply to the renal pelvis. A renal pelvic dimension of > 5 mm at any
      gestational age is unusual and dilatation beyond this level should prompt a
      detailed post-natal urological investigation.

PMID- 8535725
TI  - Treatment of enuresis risoria in children by self-administered electric and
      imaginary shock.
AB  - OBJECTIVE: To treat enuresis risoria (giggle micturition) by a self-administered
      electric and imaginary shock and to evaluate the outcome after behavioural
      therapy. PATIENTS AND METHODS: Six boys and three girls with enuresis risoria
      were evaluated and treated. The mean age at referral was 10.4 years (range 5.7
      14.2). All children had episodes of involuntary complete bladder emptying
      triggered by hearty laughter or giggling. The frequency ranged from four times
      per day to twice a week. No other voiding problems were noted. Five patients
      (four boys and one girl, mean age 10.2 years, range 5.7-14.2) received
      conditioning training which consisted largely of the self-administration of a
      harmless, painless electric shock to the back of one hand, at the moment when
      micturition was induced by laughter, leading to inhibition of the voiding reflex.
      Later, the electric shock was replaced by an imaginary shock. Training was
      undertaken on an outpatient basis. A mean of eight sessions, each of 45 min
      duration, was necessary to train the children. The mean follow-up was 26 months
      (range 12-51). RESULTS: The frequency of wetting was reduced by a mean of 89% in
      all children 1 year after the successful completion of the training. In three
      children, followed for 2 years, this result stabilized at that proportion. One of
      these children, followed for > 3 years, gradually reverted to the original
      pattern of daily wetting and another patient, with a follow-up of > 4 years,
      maintained an 86% reduction of wetting incidents. CONCLUSION: Until now, there
      was no specific treatment for enuresis risoria and not all patients outgrow the
      problem; this experimental conditioning programme shows promise in diminishing
      wetting incidents. However, the programme needs further testing in a prospective
      study.

PMID- 8535726
TI  - Modification of therapy based on videourodynamics in neurologically normal
      children: Southampton 1988-1993.
AB  - OBJECTIVE: To follow up a previously investigated group of enuretic children to
      assess their current situation and to determine if their previous treatment was
      appropriate. PATIENTS AND METHODS: A group of 57 neurologically normal, enuretic
      children (mean age 10 years) were followed for a mean of 19 months (range 3-54)
      after the establishment of a working diagnosis with videourodynamics. Many of
      these children had previously been under medical follow-up for long periods with
      no change in their enuresis. Depending on the urodynamic diagnosis, a therapeutic
      strategy was instigated and continued for an appropriate duration. Normal
      children were simply reassured. RESULTS: Currently, 44 patients (77%) are
      completely or very nearly dry. CONCLUSION: Videourodynamics, although a traumatic
      procedure, provides information unobtainable from other sources. Treatment based
      on this information gives good results and may prevent years of unnecessary or
      inappropriate therapy, and psychological problems. Ambulatory studies may yield
      more useful information.

PMID- 8535727
TI  - Diuresis and voiding pattern in healthy schoolchildren.
AB  - OBJECTIVE: To analyse how differences in diuresis affect the normal pattern of
      micturition of healthy children. SUBJECTS AND METHODS: Two hundred and six
      healthy continent schoolchildren, aged 7-15 years, completed a frequency/volume
      chart for 24 h by recording the time and volume of each micturition. Several
      diuresis variables were calculated from these charts and compared with sex, age,
      oral fluid intake, functional bladder capacity, voiding intervals and volumes.
      RESULTS: The weight-corrected mean diuresis per 24 h varied 10-fold between
      individuals, independently of recorded fluid intake. In the majority, the
      diuresis decreased during the night, but the opposite diurnal pattern occurred in
      12% of the children. The individual night-time diuresis was positively correlated
      with functional bladder capacity and the daytime diuresis was positively
      correlated with voiding frequency. CONCLUSIONS: The weight-corrected diuresis
      varies many-fold among healthy continent children. A substantial proportion has a
      reversed diurnal pattern with a larger diuresis during the night. The individual
      bladder size is adapted to accommodate their typical nightly urine production.

PMID- 8535728
TI  - The use of the hCG stimulation test in the endocrine evaluation of
      cryptorchidism.
AB  - OBJECTIVE: To review retrospectively the value of the human chorionic
      gonadotrophin (hCG) test in the evaluation of prepubertal boys with bilateral
      impalpable testes. SUBJECTS AND METHODS: The study comprised 31 boys investigated
      between 1974 and 1990 at the Hospital for Sick Children, London. All boys had an
      hCG test consisting of three intramuscular injections of hCG on successive days
      at a daily dose dependent on their age (< 1 year old, 500 units; 1-10 years, 1000
      units; > 10 years, 1500 units). Blood samples were taken before the first dose
      and 24 h after the last dose and the level of plasma testosterone assessed and
      expressed as a pre/post ratio. RESULTS: Eight boys had no response to hCG, due to
      anorchia. One boy had no response to hCG but had bilateral atrophic intra
      abdominal testes. Twenty-two boys responded to hCG and had testes whose size was
      related to the degree of testosterone elevation after this stimulatory test. The
      hCG test therefore had a positive predictive value of 89% and a negative
      predictive value of 100%. There was a quantitative difference in testosterone
      response between 14 boys who had bilateral intra-abdominal testes of 'normal'
      volume (median pre/post ratio, 11.4) and nine boys who had an otherwise reduced
      volume of testes (dysplastic or unilateral intra-abdominal) (median pre/post
      ratio of 4; P = 0.02). CONCLUSION: The hCG test is a valid indicator of the
      presence of functioning testicular tissue. It is predictive of anorchia and a
      good response to hCG suggests the presence of testes sufficiently large for
      orchidopexy.

PMID- 8535729
TI  - Non-refluxing minimal irritation ureteric stent.

PMID- 8535730
TI  - Umbilical transposition in neonates with bladder exstrophy.

PMID- 8535731
TI  - Obturator herniation following radical cystoprostatectomy.

PMID- 8535732
TI  - An unusually large anterior urethral stone.

PMID- 8535733
TI  - Anabolic steroid abuse and male infertility.

PMID- 8535734
TI  - Fracture of the penis: magnetic resonance imaging of the rupture of the corpus
      cavernosum.

PMID- 8535735
TI  - Mucinous (colloid) adenocarcinoma of the prostate.

PMID- 8535736
TI  - Laparoscopy for undescended testes: embryological considerations.

PMID- 8535738
TI  - Ureteric injury following renal transplant needle core biopsy.

PMID- 8535737
TI  - Parietal wall urinary extravasation and abdominal wall hernia secondary to
      posterior urethral valves in a neonate.

PMID- 8535740
TI  - Acute reactive polyarthritis after intravesical bacillus Calmette-Guerin
      instillation.

PMID- 8535739
TI  - Transvesical endoscopic drainage of a seminal vesicle cyst.

PMID- 8535741
TI  - EMLA during local anaesthetic vasectomy.

PMID- 8535742
TI  - Breast lump--an unusual presentation of renal cell carcinoma.

PMID- 8535743
TI  - Intravesical mitozantrone in recurrent superficial bladder cancer.

PMID- 8535744
TI  - Trash penis.

PMID- 8535745
TI  - Trash penis.

PMID- 8535746
TI  - Extraction of an intravesical thermometer using a flexible cystoscope.

PMID- 8535747
TI  - Ethical issues in medical publishing.

PMID- 8535748
TI  - Ethical issues in male sterilization in developing countries.

PMID- 8535749
TI  - Ethical issues and the law.

PMID- 8535750
TI  - Ethical issues in clinical research: the role of the research ethics committee.

PMID- 8535751
TI  - Ethical issues in clinical trials.

PMID- 8535752
TI  - Ethical issues in cancer treatment.

PMID- 8535753
TI  - Ethical issues in the pharmaceutical industry.

PMID- 8535754
TI  - Ethical issues in healthcare prioritization: a medical viewpoint.

PMID- 8535755
TI  - Ethical issues in urology: the patient's perspective.

PMID- 8535756
TI  - Ethical issues in healthcare prioritization: a political viewpoint.

PMID- 8535757
TI  - Ethical issues in the economics of rationing healthcare.

PMID- 8535758
TI  - Ethical issues and molecular biology in urology.

PMID- 8535759
TI  - Ethical and regulatory issues in gene therapy.

PMID- 8535760
TI  - Ethical issues in children with genital ambiguity.

PMID- 8535761
TI  - Ethical issues of diagnosis in utero.

PMID- 8535762
TI  - Ethical issues in assisted reproductive medicine: a pragmatic approach.

PMID- 8535763
TI  - Ethical and legal responses to patients who refuse consent to treatment.

PMID- 8535764
TI  - Ethical issues in the developing world.

PMID- 8535765
TI  - Ethical issues in renal transplantation in developing countries.

PMID- 8535766
TI  - The current hype in hypospadiology.

PMID- 8535767
TI  - Buccal mucosa grafts in hypospadias surgery.

PMID- 8535768
TI  - Hypospadias repair: the two-stage alternative.
AB  - One-stage repairs for hypospadias are attractive in concept and are currently in
      vogue, but many surgeons remain unhappy with their inherent limitations and
      drawbacks. Two-stage repair, reconstructing the new urethra with a full-thickness
      skin graft, offers a realistic alternative and the method described here can be
      applied to almost any degree of deformity, be it a simple primary case or salvage
      of a multi-operated and skin-deficient hypospadias 'cripple'. From a personal
      series of over 600 cases the author concludes that a two-stage operation is an
      acceptable price to pay for a repair that offers unique versatility, excellent
      reliability and a sophistication of function and aesthetics that is hard to
      achieve with one-stage methods.

PMID- 8535769
TI  - Hypospadias repair: current principles and procedures.

PMID- 8535770
TI  - Pediatric gastrointestinal endoscopy.
AB  - Development of smaller instruments and emergence of pediatric gastroenterology as
      a legitimate and growing subspecialty have been primary factors involved in
      effective utilization of gastrointestinal endoscopy in the care of infants and
      children. Endoscopic gastrointestinal procedures are now common in most major
      pediatric centers, and they can be safely performed on small infants, including
      newborns. This review of pediatric endoscopy presents many of the standard
      techniques that are applied in most pediatric centers in the United States. Some
      of the important issues and differences between pediatric and adult patients with
      gastrointestinal diseases are discussed.

PMID- 8535771
TI  - Twenty-four hour esophageal pH monitoring: technique and application.
AB  - In the last three decades, esophageal pH monitoring has progressed from an
      exclusively laboratory-based physiological research tool to a routine outpatient
      clinical investigation in patients with one of the most common gastrointestinal
      disorders. Technological advancement has considerably simplified both the
      procedure and the interpretation of data obtained, and there is currently
      reasonable consensus as to the parameters that best discriminate between
      physiological and pathological gastroesophageal reflux. There remains a need for
      internationally agreed definitions and standards, particularly with regard to
      calculation of these parameters, which would improve comparability of future
      research studies from different centers. Clinical applications of the technique
      have increased with our enhanced knowledge of the protean clinical manifestations
      of reflux disease. The advent of potent pharmacotherapy and the recognition of a
      need for ongoing treatment in many patients will ensure that the most sensitive
      test for the diagnosis of gastroesophageal reflux disease will remain an
      essential part of the investigation of upper gastrointestinal symptoms.

PMID- 8535772
TI  - Gastrointestinal cancer: epidemiological data and premalignant lesions.
AB  - A variety of cancers develop in the gastrointestinal tract. Knowledge of the
      epidemiological risk factors and the premalignant changes associated with these
      cancers may help prevent or decrease the incidence of these malignancies. We
      enumerate the risk factors and discuss the premalignant lesions associated with
      each cancer in light of the many epidemiological and clinical studies important
      to practicing gastroenterologists.

PMID- 8535773
TI  - Nitric oxide and liver disease.
AB  - Nitric oxide is a highly reactive, diffusible gas that is produced by many
      tissues, and it exerts a range of physiological and pathophysiological effects.
      The liver is one organ clearly influenced by nitric oxide, and acute versus
      chronic exposure to this substance has been associated with distinct patterns of
      liver disease. Bacterial infections, including the sepsis syndrome, acutely
      increase nitric oxide systemically and may lead to acute hepatic dysfunction. We
      review etiology, diagnosis, and treatment of cholestasis associated with these
      infections, because this condition in particular has been linked to nitric oxide.
      Chronic increases in nitric oxide may cause the hyperdynamic circulation seen in
      cirrhosis and portal hypertension. Therefore, we also review etiology, diagnosis,
      and treatment of the hepatorenal and hepatopulmonary syndromes, because both
      these syndromes occur in end-stage liver disease, and they may be linked to
      nitric oxide as well. An appreciation of nitric oxide and its evolving role in
      hepatology may be important to understand the pathogenesis of and treatment
      strategies for these different types of liver disease.

PMID- 8535774
TI  - A practical approach to nutritional support in liver disease.
AB  - Nutritional problems are very common in patients with liver disease. The
      underlying liver disease will cause anorexia, nausea, and a poor appetite. In
      addition, alcohol acts as "cheap calories" and may be an added problem.
      Physicians taking care of patients with liver disease often place them on
      restrictive diets that compound the nutritional problem. Patients must be
      addressed for both the liver disease and the nutritional problems its treatment
      may create. One very important fact is that the majority of patients with liver
      disease will tolerate standard formulas that are much more "cost-effective" for
      the patients. How to calculate caloric and protein needs and how to select
      certain formulas are addressed. The results that show nutritional support is
      beneficial in decreasing mortality and morbidity are reviewed.

PMID- 8535775
TI  - Infectious colitides in patients with acquired immunodeficiency syndrome.
AB  - Diarrhea is a common problem in patients with acquired immunodeficiency syndrome
      (AIDS), and infections of the colon constitute a significant etiology.
      Cytomegalovirus (CMV) is the most common opportunistic infection of the colon in
      patients with AIDS, and it can involve any portion of the colon and the
      gastrointestinal tract. Because CMV is potentially treatable with either
      ganciclovir or foscarnet, it is important to evaluate endoscopically the entire
      colon of patients with AIDS with protracted diarrhea and no cause identifiable
      with routine stool and laboratory tests. In addition to CMV, there are a variety
      of other viral, bacterial, protozoal, and fungal infections seen in patients with
      AIDS. A thorough evaluation will help identify these pathogens, and those that
      are treatable can be given appropriate therapy.

PMID- 8535776
TI  - The antiphospholipid syndrome and ischemic colitis.

PMID- 8535777
TI  - Medical therapy of pruritus of cholestasis.
AB  - Pruritus is one of the most frequent and distressing symptoms of chronic
      cholestasis. Its pathogenesis is unknown. Agents implicated include bile acids
      and other retained constituents of bile, as well as endogenous opioids. Therapy
      is empiric and not universally effective. Attempts have been made to remove
      pruritogens from the body with bile acid sequestrants, to increase their
      excretion with enzyme inducers, and to block their action with opiate
      antagonists. The pros and cons of individual agents and an overall approach to
      therapy are discussed.

PMID- 8535778
TI  - Ribosomes seen through a glass less darkly.
AB  - Electron microscopists have made important progress recently in their quest to
      determine the structure of the ribosome. New insights into the mechanism of
      protein synthesis are beginning to emerge, and substantial progress is likely in
      the immediate future.

PMID- 8535779
TI  - Structures and mechanisms of glycosyl hydrolases.
AB  - The wealth of information provided by the recent structure determinations of many
      different glycosyl hydrolases shows that the substrate specificity and the mode
      of action of these enzymes are governed by exquisite details of their three
      dimensional structures rather than by their global fold.

PMID- 8535780
TI  - Weighing the evidence for structure: electrospray ionization mass spectrometry of
      proteins.

PMID- 8535781
TI  - Modeling of the three-dimensional structure of proteins with the typical leucine
      rich repeats.
AB  - BACKGROUND: Leucine-rich repeats (LRRs) are present in proteins with diverse
      functions. The horseshoe-shaped structure of a ribonuclease inhibitor (RI), with
      a parallel beta sheet lining the inner circumference of the horseshoe and alpha
      helices flanking its outer circumference, is the only X-ray structure containing
      these repeats to be determined. Despite the fact that the lengths and sequences
      of the RI repeats differ from those of the most commonly occurring LRRs, it was
      deemed worthwhile to derive a three-dimensional structural framework of these
      more typical LRR proteins, using the RI structure as a template. RESULTS:
      Sequence alignments of 569 LRRs from 68 proteins were obtained by a profile
      search and used in a comparative sequence analysis to distinguish between
      residues with a probable structural role and those which seemed essential for
      function. This knowledge, along with the known atomic structure of RI, was used
      to model the three-dimensional structure of the most common LRR units. These
      modeled units were then used to build the three-dimensional structure of the
      extracellular domain of the thyrotropin receptor (TSHR)--a 'typical' LRR protein.
      CONCLUSIONS: The modeled TSHR structure adopts a non-globular arrangement,
      similar to that in RI. The beta regions of this typical LRR protein are the same
      as in the RI structure, whereas the alpha helices are shorter and the
      conformations of the alpha beta and beta alpha connections are different. As a
      result of these differences it was not possible to pack together typical LRR
      units using repeats such as those found in RI. This mutually exclusive
      relationship is supported by sequence analysis. The predicted structure of the
      typical LRRs obtained here can be used to build models for any of the known LRR
      proteins and the approach used for the prediction could be applied to other
      proteins containing internal repeats.

PMID- 8535782
TI  - Mechanistic implications from the structure of a catalytic fragment of Moloney
      murine leukemia virus reverse transcriptase.
AB  - BACKGROUND: Reverse transcriptase (RT) converts the single-stranded RNA genome of
      a retrovirus into a double-stranded DNA copy for integration into the host
      genome. This process requires ribonuclease H as well as RNA- and DNA-directed DNA
      polymerase activities. Although the overall organization of HIV-1 RT is known
      from previously reported crystal structures, no structure of a complex including
      a metal ion, which is essential for its catalytic activity, has been reported.
      RESULTS: Here we describe the structures at 1.8 Angstrum resolution of a
      catalytically active fragment of RT from Moloney murine leukemia virus (MMLV) and
      at 2.6 Angstrum of a complex of this fragment with Mn2+ coordinated in the
      polymerase active site. On the basis of similarities with HIV-1 RT and rat DNA
      polymerase beta, we have modeled template/primer and deoxyribonucleoside 5'
      triphosphate substrates into the MMLV RT structure. CONCLUSIONS: Our model, in
      the context of the disposition of evolutionarily conserved residues seen here at
      high resolution, provides new insights into the mechanisms of catalysis,
      fidelity, processivity and discrimination between deoxyribose and ribose
      nucleotides.

PMID- 8535783
TI  - Hydration structure of a collagen peptide.
AB  - BACKGROUND: The collagen triple helix is a unique protein motif defined by the
      supercoiling of three polypeptide chains in a polyproline II conformation. It is
      a major domain of all collagen proteins and is also reported to exist in proteins
      with host defense function and in several membrane proteins. The triple-helical
      domain has distinctive properties. Collagen requires a high proportion of the
      post-translationally modified imino acid 4-hydroxyproline and water to stabilize
      its conformation and assembly. The crystal structure of a collagen-like peptide
      determined to 1.85 Angstrum showed that these two features may be related.
      RESULTS: A detailed analysis of the hydration structure of the collagen-like
      peptide is presented. The water molecules around the carbonyl and hydroxyprolyl
      groups show distinctive geometries. There are repetitive patterns of water
      bridges that link oxygen atoms within a single peptide chain, between different
      chains and between different triple helices. Overall, the water molecules are
      organized in a semi-clathrate-like structure that surrounds and interconnects
      triple helices in the crystal lattice. Hydroxyprolyl groups play a crucial role
      in the assembly. CONCLUSIONS: The roles of hydroxyproline and hydration are
      strongly interrelated in the structure of the collagen triple helix. The
      specific, repetitive water bridges observed in this structure buttress the triple
      helical conformation. The extensively ordered hydration structure offers a good
      model for the interpretation of the experimental results on collagen stability
      and assembly.

PMID- 8535784
TI  - The prosegment-subtilisin BPN' complex: crystal structure of a specific
      'foldase'.
AB  - BACKGROUND: The folding of the bacterial protease subtilisin BPN' (SBT) is
      dependent on its 77-residue prosegment, which is then autocatalytically removed
      to give the mature enzyme. Mature subtilisin represents a class of proteins that
      lacks an efficient folding pathway. Refolding of mature SBT is extremely slow
      unless catalyzed by the independently expressed prosegment, leading to a
      bimolecular complex. RESULTS: We report the crystal structure at 2.0 A resolution
      of the prosegment-SBT complex and consider its implications for prosubtilisin
      BPN' maturation and folding catalysis. The prosegment forms a compact domain that
      binds SBT through an extensive interface involving the enzyme's two parallel
      surface helices (residues 104-116 and 133-144), supplying negatively charged caps
      to the N termini of these helices. The prosegment C terminus binds in the enzyme
      active site in a product-like manner, with Tyr77 in the P1 binding pocket.
      CONCLUSIONS: The structure of the complex supports a unimolecular mechanism for
      prosubtilisin cleavage, involving a 25 A rearrangement of the SBT N terminus in a
      late folding step. A mechanism of folding catalysis in which the two helices and
      their connecting beta strand form a prosegment-stabilized folding nucleus is
      proposed. While this putative nucleus is stabilized by prosegment binding, the N
      terminal and C-terminal subdomains of SBT could fold by propagation.

PMID- 8535785
TI  - The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO:
      lessons for inhibitor design.
AB  - BACKGROUND: HIV reverse transcriptase (RT) is a key target of anti-AIDS
      therapies. Structural studies of HIV-1 RT, unliganded and complexed with
      different non-nucleoside inhibitors (NNIs), have pointed to a common mode of
      binding and inactivation through distortion of the polymerase catalytic site by
      NNIs containing two hinged rings. The mode of binding of the TIBO family of
      inhibitors is of interest because these compounds do not fit the two-hinged-ring
      model. RESULTS: The structure of HIV-1 RT complexed with 9-chloro-TIBO (R82913)
      has been determined at 2.6 A resolution. As reported for the lower resolution
      analysis of another TIBO compound, this inhibitor binds at the same site as other
      NNIs, but our higher resolution study reveals the Cl-TIBO is distorted from the
      conformation seen in crystals of the inhibitor alone. This allows Cl-TIBO to
      mimic the binding of NNIs containing two hinged rings. Inhibitor-protein
      interactions are again predominantly hydrophobic and the protein conformation
      corresponds to that seen in complexes with other tight-binding NNIs. CONCLUSIONS:
      Although Cl-TIBO is chemically very different from other NNIs, it achieves
      remarkable spatial equivalence and shape complementarity with other NNIs on
      binding to RT. Comparison of the different RT-NNI complexes suggests
      modifications to the TIBO group of inhibitors which might enhance their binding
      and hence, potentially, their therapeutic efficacy.

PMID- 8535786
TI  - Common themes in redox chemistry emerge from the X-ray structure of oilseed rape
      (Brassica napus) enoyl acyl carrier protein reductase.
AB  - BACKGROUND: Enoyl acyl carrier protein reductase (ENR) catalyzes the NAD(P)H
      dependent reduction of trans-delta 2-enoyl acyl carrier protein, an essential
      step in de novo fatty acid biosynthesis. Plants contain both NADH-dependent and
      separate NADPH-dependent ENR enzymes which form part of the dissociable type II
      fatty acid synthetase. Highly elevated levels of the NADH-dependent enzyme are
      found during lipid deposition in maturing seeds of oilseed rape (Brassica napus).
      RESULTS: The crystal structure of an ENR-NAD binary complex has been determined
      at 1.9 A resolution and consists of a homotetramer in which each subunit forms a
      single domain comprising a seven-stranded parallel beta sheet flanked by seven
      alpha helices. The subunit has a topology highly reminiscent of a dinucleotide
      binding fold. The active site has been located by difference Fourier analysis of
      data from crystals equilibrated in NADH. CONCLUSIONS: The structure of ENR shows
      a striking similarity with the epimerases and short-chain alcohol dehydrogenases,
      in particular, 3 alpha,20 beta-hydroxysteroid dehydrogenase (HSD). The similarity
      with HSD extends to the conservation of a catalytically important lysine that
      stabilizes the transition state and to the use of a tyrosine as a base--with
      subtle modifications arising from differing requirements of the reduction
      chemistry.

PMID- 8535787
TI  - Crystal structure of the catalytic domain of a bacterial cellulase belonging to
      family 5.
AB  - BACKGROUND: Cellulases are glycosyl hydrolases--enzymes that hydrolyze glycosidic
      bonds. They have been widely studied using biochemical and microbiological
      techniques and have attracted industrial interest because of their potential in
      biomass conversion and in the paper and textile industries. Glycosyl hydrolases
      have lately been assigned to specific families on the basis of similarities in
      their amino acid sequences. The cellulase endoglucanase A produced by Clostridium
      cellulolyticum (CelCCA) belongs to family 5. RESULTS: We have determined the
      crystal structure of the catalytic domain of CelCCA at a resolution of 2.4 A and
      refined it to 1.6 A. The structure was solved by the multiple isomorphous
      replacement method. The overall structural fold, (alpha/beta)8, belongs to the
      TIM barrel motif superfamily. The catalytic centre is located at the C-terminal
      ends of the beta strands; the aromatic residues, forming the substrate-binding
      site, are arranged along a long cleft on the surface of the globular enzyme.
      CONCLUSIONS: Strictly conserved residues within family 5 are described with
      respect to their catalytic function. The proton donor, Glu170, and the
      nucleophile, Glu307, are localized on beta strands IV and VII, respectively, and
      are separated by 5.5 A, as expected for enzymes which retain the configuration of
      the substrate's anomeric carbon. Structure determination of the catalytic domain
      of CelCCA allows a comparison with related enzymes belonging to glycosyl
      hydrolase families 2, 10 and 17, which also display an (alpha/beta)8 fold.

PMID- 8535788
TI  - The crystal structure of a cyanogenic beta-glucosidase from white clover, a
      family 1 glycosyl hydrolase.
AB  - BACKGROUND: beta-glucosidases occur in a variety of organisms and catalyze the
      hydrolysis of aryl and alkyl-beta-D-glucosides as well as glucosides with only a
      carbohydrate moiety (such as cellobiose). The cyanogenic beta-glucosidase from
      white clover (subsequently referred to as CBG) is responsible for the cleavage of
      cyanoglucosides. Both CBG and the cyanoglucosides occur within the plant cell
      wall where they are found in separate compartments and only come into contact
      when the leaf tissue experiences mechanical damage. This results in the eventual
      production of hydrogen cyanide which acts as a deterrent to grazing animals. beta
      glucosidases have been assigned to particular glycosyl hydrolase families on the
      basis of sequence similarity; this classification has placed CBG in family 1
      (there are a total of over 40 families) for which a three-dimensional structure
      has so far not been determined. This is the first report of the three-dimensional
      structure of a glycosyl hydrolase from family 1. RESULTS: The crystal structure
      of CBG has been determined using multiple isomorphous replacement. The final
      model has been refined at 2.15 A resolution to an R factor of 18.9%. The overall
      fold of the molecule is a (beta/alpha)8 [or (alpha/beta)8] barrel (in common with
      a number of glycosyl hydrolases) with all residues located in a single domain.
      CONCLUSIONS: Sequence comparisons between beta-glucosidases of the same family
      show that residues Glu183 and Glu397 are highly conserved. Both residues are
      positioned at the end of a pocket located at the C terminus of the barrel and
      have been assigned the respective roles of proton donor and nucleophile on the
      basis of inhibitor-binding and mutagenesis experiments. These roles are
      consistent with the environments of the two residues. The pocket itself is
      typical of a sugar-binding site as it contains a number of charged, aromatic and
      polar groups. In support of this role, we present crystallographic data on a
      possible product complex between CBG and glucose, resulting from co
      crystallization of the native enzyme with its natural substrate, linamarin.

PMID- 8535789
TI  - The three-dimensional structure of 6-phospho-beta-galactosidase from Lactococcus
      lactis.
AB  - BACKGROUND: The enzyme 6-phospho-beta-galactosidase hydrolyzes phospholactose,
      the product of a phosphor-enolpyruvate-dependent phosphotransferase system. It
      belongs to glycosidase family 1 and no structure has yet been published for a
      member of this family. RESULTS: The crystal structure of 6-phospho-beta
      galactosidase was determined at 2.3 A resolution by multiple isomorphous
      replacement, using the wild-type enzyme and a designed cysteine mutant. A second
      crystal form, found with the mutant enzyme, was solved by molecular replacement,
      yielding the conformation of two chain loops that are invisible in the first
      crystal form. The active center, located through catalytic residues identified in
      previous studies, cannot be accessed by the substrate if the two loops are in
      their defined conformation. The enzyme contains a (beta alpha)8 barrel and the
      relationship of its chain fold to that of other glycosidases has been quantified.
      As a side issue, we observed that a cysteine point mutant designed for X-ray
      analysis crystallized mainly as a symmetric dimer around an intermolecular
      disulfide bridge formed by the newly introduced cysteine. CONCLUSIONS: The
      presented analysis provides a basis on which to model all other family 1 members
      and thereby will help in elucidating the catalytic mechanisms of these sequence
      related enzymes. Moreover, this enzyme belongs to a superfamily of glycosidases
      sharing a (beta alpha)8 barrel with catalytic glutamates/aspartates at the ends
      of the fourth and the seventh strands of the beta barrel.

PMID- 8535790
TI  - Expanding metal stents in the gastrointestinal tract.

PMID- 8535791
TI  - Streptococcal necrotizing fasciitis in Gloucestershire: 1994.

PMID- 8535792
TI  - Mesenteric ischaemia: a multidisciplinary approach.
AB  - Mesenteric ischaemia may result from a wide range of pathological processes, each
      possessing unique clinical features, diagnostic difficulties, management
      strategies and outcome. Regardless of aetiology, prognosis depends crucially on
      rapid diagnosis and institution of treatment to prevent, or at least to minimize,
      bowel infarction. Progress in understanding the pathophysiology of mesenteric
      ischaemia has led to novel methods of treatment, so that in some circumstances
      therapy may be purely medical. More often surgery is required and is frequently
      life saving. Percutaneous transcatheter techniques are increasingly employed in
      both diagnosis and treatment. Close cooperation between radiologists, physicians
      and surgeons is therefore necessary if clinical outcome is to be optimized. This
      paper reviews the modern interdisciplinary management of mesenteric ischaemia in
      the light of recent advances.

PMID- 8535793
TI  - Manipulation of local and systemic host defence in the prevention of
      perioperative sepsis.
AB  - This review addresses some of the immunological issues surrounding the complex
      problem of perioperative sepsis. It identifies an immunological paradox between
      the relative immunosuppression of the immediate postoperative period and the
      relative immune activation of established sepsis, in addition to discussing
      current knowledge of the mechanisms surrounding these phenomena. Much remains
      unknown about perioperative immunoregulation; there are a number of potential
      mechanisms, however, whereby local and systemic immune defences can be modified
      or enhanced. Provided patients at risk can be identified, such manipulations may
      find application in preventing infection and sepsis after surgery.

PMID- 8535794
TI  - Difference in expression of CD44 splice variants between proximal and distal
      adenocarcinoma of the large bowel.
AB  - To help determine whether adenocarcinomas of the proximal and distal large bowel
      reflect distinct entities, the expression of two splice variants of the
      metastasis-associated cell adhesion molecule CD44, carrying exons v5 and v6
      respectively, was investigated retrospectively in fresh frozen samples of 23
      proximal and 41 distal carcinomas by immunohistochemical staining with specific
      anti-CD44v5 monoclonal antibody VFF8 and anti-CD44v6 monoclonal antibodies VFF4
      and VFF7. Tumours were staged as: Dukes A, 0; Dukes B, 27; Dukes C, 31; and Dukes
      'D', six. Compared with distal tumours, proximal lesions expressed significantly
      more CD44v5 (96 versus 87 per cent, P = 0.02) and CD44v6 (83 versus 61 per cent,
      P = 0.01). CD44v5 and CD44v6 are considered markers for tumour progression and
      aggressive behaviour. Their high expression in proximal carcinomas seems to
      contrast with the general belief that these tumours show less aggressive
      behaviour than left-sided lesions. Further study of the biological significance
      of the expression of CD44 splice variants is therefore needed.

PMID- 8535795
TI  - Recurrence and reoperation after strictureplasty for obstructive Crohn's disease:
      long-term results [corrected].
AB  - Strictureplasty extends the surgical options for the treatment of obstructive
      Crohn's disease. Over 15 years, 52 patients had 241 strictureplasties at 76
      operations with no operative mortality and with septic complications in only two
      patients (4 percent). Median (range) follow-up was 49.5 (1-182) months. Nineteen
      patients (36 percent) required a second operation for Crohn's disease between 1
      and 57 months after first strictureplasty. Most symptomatic recurrence was caused
      by new segments of stricturing or perforating disease, and recurrence of Crohn's
      disease was noted at only nine strictureplasty sites (3.7 percent) in four
      patients. Seven patients (13 percent) required a third operation for Crohn's
      disease. Patients undergoing strictureplasty alone were no more likely to require
      reoperation than those who had a concomitant resection at the first procedure (X2
      = 0.619, P > 0.2). The reoperation rates after first and second operations were
      similar (X2 = 0.021, P > 0.2). Minimal surgery does not appear to lead to an
      accelerated or additional need for subsequent operation. Strictureplasty provides
      a safe, effective and rapid procedure to restore patients to good health while
      preserving the intestine and may be recommended for carefully selected strictures
      as an adjunct to conventional excisional surgical treatment.

PMID- 8535796
TI  - Physiological changes after Delorme's procedure for full-thickness rectal
      prolapse.
AB  - Anal sphincter pressures, rectal compliance and sensation in 19 women of mean age
      77 (range 57-94) years were studied before and after Delorme's procedure for full
      thickness rectal prolapse. No patient had significant problems with defaecation
      after operation. There were no significant changes in anal sphincter pressures
      but the volume of first rectal sensation decreased from a median of 140 ml before
      surgery to 65 ml after the procedure (P = 0.01) and the maximum tolerated rectal
      volume declined from a median of 249 ml to 120 ml (P = 0.001). Rectal compliance
      was reduced from a median of 142.9 ml/kPa to 12.2 ml/kPa (P = 0.002). Improved
      rectal sensation and lowered compliance are associated with a reduced incidence
      of defaecatory problems after Delorme's procedure.

PMID- 8535797
TI  - Endotoxaemia and cytokine production in experimental colitis.
AB  - Systemic endotoxaemia is a well recognized feature of inflammatory bowel disease
      but its pathogenic role remains uncertain. This study examined plasma endotoxin
      and cytokine concentrations and the acute-phase protein response in a hapten
      induced model of experimental colitis. On days 2, 8 and 14 after induction of
      colitis with trinitrobenzenesulphonic acid in ethanol (TNBS-E), plasma endotoxin,
      immunoglobulin (Ig) G and IgM endotoxin-core antibody (EndoCAb), tumour necrosis
      factor (TNF), interleukin (IL) 6 and alpha 2-macroglobulin (alpha 2M)
      concentrations and colon macroscopic inflammation score were determined. At all
      time points there was significant colonic inflammation when compared with control
      values (P < 0.0001). Animals treated with TNBS-E had raised concentrations of
      endotoxin at all time points (P < 0.04). In TNBS-E-treated animals EndoCAb
      concentrations were reduced on day 2 (P < 0.0001) and later increased. There were
      increases in IL-6 and alpha 2M concentrations in TNBS-E-treated animals but no
      significant change in TNF concentrations. Endotoxin concentrations correlated
      with macroscopic inflammation score, IL-6 and alpha 2M concentrations. There was
      a less consistent correlation between EndoCAb concentrations and these
      parameters. These results suggest that endotoxin is a mediator of the systemic
      response in this model of experimental colitis.

PMID- 8535798
TI  - Microvascular disease and anastomotic dehiscence in the colon.
AB  - Platelet-derived serotonin released in response to tissue manipulation during
      surgery may contribute to mesenteric arterial vasospasm leading to postoperative
      anastomotic leakage after colorectal resection. Organ bath experiments were used
      to demonstrate the efficacy of naftidrofuryl fumarate (NFT) to oppose serotonin
      induced vasoconstriction of human mesenteric arteries. Cumulative dose-response
      curves were derived with and without NFT at 10(-9) and 10(-6) mol/l
      concentrations. The difference in maximal contractility between the three sets of
      curves (n = 8 for each) was significant (P < 0.0001). Sensitivity to serotonin in
      each of the three curves was measured by calculating the concentration for half
      maximal response; differences were again significant (P < 0.0001). NFT reduced
      serotonin-induced contractility in a dose-dependent fashion in rings of human
      mesenteric arteries in vitro. This suggests a possible role for NFT in reducing
      mesenteric vasospasm in colorectal surgery.

PMID- 8535799
TI  - A 10-year prospective audit of outcome of surgical treatment for colorectal
      carcinoma.
AB  - The outcome of 555 patients who underwent surgery under the care of a surgeon
      with an interest in colorectal disease was examined prospectively over a 10-year
      period with no exclusions. There was a 4.7 percent incidence of clinical leaks
      (10 percent for anterior resection) and an overall corrected 10-year survival
      rate after curative surgery of 58, 59 and 48 percent for right colonic, left
      colonic and rectal tumours respectively. The incidence of isolated local
      recurrence was 8 percent after curative surgery for carcinoma of the rectum.
      Twenty-five percent of patients with rectal tumours required abdominoperineal
      excision. Patients who underwent curative abdominoperineal excision of the rectum
      had corrected 5- and 10-year survival rates of 48 and 36 percent, compared with
      60 and 58 percent respectively for curative anterior resection. The perioperative
      mortality rate of those undergoing palliative surgery was 8 percent, and 75
      percent died within 2 years from distant and not local disease. A policy of
      always attempting resection was validated by the fact that 99 percent of primary
      tumours were removed with a low perioperative mortality rate (4 percent overall),
      a high curative resection rate and a low morbidity rate.

PMID- 8535800
TI  - Intraoperative measurement of colonic anatomy and attachments with relevance to
      colonoscopy.
AB  - This study examined the variations in colonic length and mesenteric attachments
      in 118 patients undergoing laparotomy. Measurements were taken according to a set
      protocol with the bowel pulled medially, or towards the pubic symphysis or the
      xiphisternum, mimicking the possible displacements that may occur during
      colonoscopy. A free sigmoid loop was not present in 20 patients (17 percent)
      because of adhesions. A descending mesocolon of 10 cm or more in length was
      recorded in ten patients (8 percent) and an ascending mesocolon 10 cm or greater
      in 11 (9 percent). Some 24 patients (20 percent) had mobile splenic flexures and
      in 34 (29 percent) the mid-transverse colon reached the symphysis pubis or lower
      when pulled downwards. Mean (range) total colonic length was 114.1 (68-159) cm.
      This study helps define anatomical variations that may affect the facility, or
      otherwise, of colonoscopy.

PMID- 8535801
TI  - Varicose vein surgery and deep vein thrombosis.
AB  - A questionnaire was sent to 363 members of the Vascular Surgical Society of Great
      Britain and Ireland about their use of deep vein thrombosis (DVT) prophylaxis at
      the time of varicose vein surgery. Replies were received from 289 surgeons (80
      percent), of whom only 29 percent regarded varicose veins as an important risk
      factor for DVT. Only 12 percent used subcutaneous heparin prophylaxis routinely,
      while 71 percent did so selectively, being influenced by a history of
      thromboembolism (95 percent), obesity (47 percent), age (35 percent), recurrent
      varicose veins (22 percent) and inpatient status (16 percent). At the end of the
      operation 52 percent applied crepe bandages, 25 percent other bandages, 13
      percent stockings and 10 percent Tubigrip. Subsequently, antiembolism stockings
      were prescribed by 55 percent. There is a wide variation in opinion regarding DVT
      prophylaxis for patients having varicose vein surgery, which has both clinical
      and medicolegal implications.

PMID- 8535802
TI  - Laparoscopic adrenalectomy.

PMID- 8535803
TI  - Cusum as an aid to early assessment of the surgical trainee.
AB  - Tests of knowledge, aptitude and psychomotor skills have been used to assess and
      select surgical trainees but none of these is reliable in the long term. The
      industrial quality-control method of the cusum was used to assess performance
      progress in 17 surgical trainees. Trainees were assessed on their ability to
      perform, independently, selected surgical operations using the criterion of
      procedure duration. Cusum profiles were compared with scores from at least four
      independent assessors using a modified Royal Australasian College of Surgeons'
      mentor form. The cusum identified all trainees who were considered either
      satisfactory or less able by their mentors. This objective evaluation was
      reliable after 25 procedures, whether for appendicectomy or combined with
      herniorrhaphy and cholecystectomy. Evaluation of surgical performance using the
      cusum may prove to be a more objective tool for assessing surgical trainees than
      early impressions or less clinically oriented tests.

PMID- 8535804
TI  - The Edinburgh randomized trial of axillary sampling or clearance after
      mastectomy.
AB  - Between January 1980 and October 1983, 417 patients were randomized for
      mastectomy followed by axillary node sampling or full axillary clearance. The aim
      of the study was to determine whether a standard 'four-node' axillary sample,
      followed by careful dissection of removed tissue, could accurately indicate the
      extent of local treatment required. Axillary radiotherapy was given only to
      patients with histological involvement of sampled nodes and not to any having
      axillary clearance. The incidence of involved nodes was similar for both groups,
      as were distant relapse and survival rates. Currently 62.6 percent are alive
      after clearance and 65.0 percent after sampling. A non-significant increase in
      the rate of locoregional relapse was observed for those treated by axillary node
      clearance, this being due mainly to increased relapse on the unirradiated chest
      wall (clearance 21 percent versus sampling 12 percent in patients with node
      positive disease). There was only a minor difference in axillary relapse,
      favouring axillary clearance (3.0 versus 5.4 percent). In patients with operable
      breast cancer, mastectomy with axillary node sampling gives equal control to
      mastectomy with axillary node clearance but, as morbidity is greater, surgical
      clearance of the axilla is the preferred option.

PMID- 8535805
TI  - Impact of fine-needle aspiration cytology, ultrasonography and mammography on
      open biopsy rate in patients with benign breast disease.
AB  - The management of breast disease has been influenced by breast imaging and fine
      needle aspiration cytology (FNAC) for preoperative diagnosis. To investigate the
      impact of introducing an in-clinic FNAC service on patient management, the
      pathology records of patients presenting before and after introduction of the
      service were studied. Four management changes emerged. The number of patients
      investigated by histology and/or cytology increased (from 266 to 503), as did
      specimen numbers (392 to 728). The use of pathological services changed, with
      more cytology specimens (39 to 554), fewer needle-core biopsies (62 to three) and
      fewer excision biopsies (245 to 118). The number of patients admitted for surgery
      fell, especially those with a benign histological diagnosis (174 to 49). These
      figures demonstrate a change in the management of benign breast disease, from
      surgery with histopathological diagnosis to cytological diagnosis with surgery
      only if indicated clinically or from imaging.

PMID- 8535806
TI  - Typhoid enteric perforation.
AB  - Of 306 cases of typhoid enteric perforation, 267 were reviewed retrospectively to
      determine prognostic indices and therapeutic options influencing outcome. The
      morbidity and mortality rates were 55.4 and 28.5 percent respectively, and the
      median duration of hospitalization was 18 days. On the basis of these findings, a
      prospective series of 39 patients was studied. In the preoperative period,
      aggressive resuscitation and antibiotic therapy with a combination of
      chloramphenicol, ampicillin/sulbactam and ornidazole were administered. All
      patients were given total parenteral nutrition to provide adequate metabolic
      support in the postoperative period. The morbidity and mortality rates decreased
      to 25 and 10 percent respectively, and the median hospitalization time was 12
      days. The results of this study suggest that aggressive resuscitation and a
      combined antibiotic regimen in the preoperative period, selected operative
      procedure and metabolic support decrease the morbidity and mortality of typhoid
      enteric perforation.

PMID- 8535807
TI  - Long-term follow-up of a prospective randomized study of endoscopic versus
      surgical treatment of bile duct calculi in patients with gallbladder in situ.
AB  - Eighty-three patients with bile duct calculi were entered in a prospective
      randomized study of endoscopic sphincterotomy (ES) and stone removal (group 1)
      versus surgery alone (group 2), and were followed for more than 5 years. In group
      1 endoscopic stone clearance was successful in 35 of 39 patients. Thirteen
      patients subsequently had cholecystectomy with (n = 7) or without (n = 6) biliary
      symptoms and one had a cholecystostomy for acute cholecystitis. Two patients have
      had mild biliary colic or pancreatitis. Two patients died from gallbladder
      carcinoma after 9 days and 18 months. In group 2 bile duct stones were cleared
      surgically in 37 of 41 patients. Late complications occurred in two patients
      (incisional hernia and recurrent stone). One patient with gallbladder carcinoma
      was cured and another died after 16 months. Early major and minor complications
      occurred in three and four respectively of 39 patients in group 1, and in three
      and six respectively of 41 patients in group 2. There were no deaths. During
      follow-up the total morbidity rate reached 28 percent (11 of 39) and 5 percent
      (two of 41) (P = 0.005) and the non-biliary related mortality rate was 31 percent
      (12 of 39) and 10 percent (four of 41) (P = 0.02) in groups 1 and 2 respectively.
      Nine patients in group 1 and two in group 2 died from heart disease (P = 0.02).
      Total hospital stay was 2-42 (median 13) days and 6-36 (median 16) days in groups
      1 and 2 respectively (P not significant). Endoscopic and surgical treatment of
      bile duct calculi in middle-aged and elderly patients with gallbladder in situ
      are equally effective in the long term. However, the significantly increased
      mortality rate from heart disease in patients treated endoscopically compared
      with those treated surgically might speak in favour of operation.

PMID- 8535808
TI  - Palliation of irresectable hilar cholangiocarcinoma with biliary drainage and
      radiotherapy.
AB  - Twelve patients with irresectable or recurrent hilar cholangiocarcinoma were
      treated with internal biliary drainage followed by intraluminal (iridium-192) and
      external-beam radiotherapy. Biliary drainage was accomplished by means of a
      combined surgical and interventional radiological approach. Initial biliary
      decompression was performed surgically by tumour resection, intrahepatic biliary
      enteric bypass or distal biliary-enteric anastomosis with a temporary stent.
      Maintenance of internal biliary drainage and application of intraluminal
      radiotherapy were accomplished radiologically with the use of percutaneous
      dilatation and metallic expandable biliary endoprostheses. Median survival was
      14.5 months; all 12 patients survived for at least 6 months. Early complications
      during radiotherapy were minor and included two patients with cholangitis and one
      with transient haemobilia. Jaundice was relieved in ten of 12 patients, while
      episodes of cholangitis were seen during long-term follow-up in 11 (median 1.5
      episodes per patient). Internal biliary drainage, in conjunction with
      radiotherapy, appears to be safe and effective palliation of irresectable or
      recurrent hilar cholangiocarcinoma. Patients can maintain a reasonable quality of
      life with an acceptable incidence of cholangitis, without the hindrance of
      external drainage devices.

PMID- 8535809
TI  - Duhamel procedure using a disposable umbilical cord clamp.

PMID- 8535810
TI  - Delayed massive haemorrhage after pancreatic and biliary surgery.
AB  - The purpose of this retrospective study was to determine the causes, symptoms and
      optimal management of massive delayed haemorrhage after pancreatic and biliary
      surgery. In a series of 686 patients who underwent major pancreatic and biliary
      surgery between 1983 and 1993, those with massive haemorrhage (necessitating more
      than 6 units packed cells within 24 h) more than 24 h after the initial surgery
      were selected. Two groups were formed, according to the aetiology of bleeding:
      bleeding caused by erosion of a major artery or that from the (gastro)intestinal
      suture line. The groups were compared with respect to bleeding parameters,
      symptoms, diagnostic and interventional procedures, and mortality. Massive
      postoperative haemorrhage occurred in 22 patients (3.2 percent): 12 (1.7 percent)
      with arterial bleeding and ten (1.5 percent) with suture-line bleeding were
      identified. Patients with arterial bleeding had a longer interval between initial
      surgery and haemorrhage (P = 0.02), more frequent septic complications (P = 0.03)
      and had a higher mortality rate than those with suture-line bleeding (50 versus 0
      percent respectively, P = 0.02). If minimally invasive diagnostic and therapeutic
      techniques are not successful, early aggressive surgical intervention is
      mandatory, including thorough exploration of the area of the resection, ligated
      artery stumps and inspection of anastomoses by enterotomy.

PMID- 8535811
TI  - Onset of oesophageal peristalsis after surgery for idiopathic achalasia.
AB  - Twenty-seven patients were treated with a Heller myotomy and Dor fundoplication;
      some peristaltic contractions occurred in seven after operation. When clinical,
      radiological and manometric data in the seven patients developing peristalsis
      were compared with findings in the other 20, there were no differences in
      symptoms, lower oesophageal sphincter pressures and lengths, relief of dysphagia
      or oesophageal calibre reduction. Oesophageal resting pressure was lower and
      oesophageal contraction amplitudes were statistically higher in patients with
      restored peristalsis, which correlated only with the amplitude of contractions 5
      cm above the lower oesophageal sphincter (P < 0.05, 95 percent confidence
      interval). Peristaltic contractions probably exist before treatment, but are
      concealed by the dilated oesophagus and the common cavity phenomenon. Achalasia
      is not necessarily associated with complete aperistalsis. No difference was found
      in the outcome of surgical treatment, and the return to peristalsis appears to be
      clinically relevant.

PMID- 8535812
TI  - Intermittent vascular exclusion of the liver (without vena cava clamping) during
      major hepatectomy.
AB  - Intermittent vascular exclusion of the liver (IVEL) combines clamping of the
      hepatic pedicle with clamping of the main hepatic veins without interruption of
      caval flow. In this retrospective study, eight cases of total IVEL and eight of
      partial IVEL were analysed (involving only the middle and left hepatic veins)
      during major hepatectomy for malignant tumours. Liver parenchyma was pathological
      in nine cases. IVEL was feasible in 16 of the 18 attempts and was efficient in
      reducing bleeding during hepatectomy in 15 cases. Mean duration of IVEL was 60.2
      (range 37-140) min, mean blood loss was 1230 (range 300-2800) ml and there were
      no postoperative complications related to the procedure. The major advantages of
      this technique of liver vascular exclusion (good tolerance and possibility of
      long duration) merit its inclusion in the list of different clamping techniques
      available for use during hepatectomy.

PMID- 8535813
TI  - Incidence, diagnosis and significance of multiple gastric cancer.
AB  - Of 2790 patients with gastric cancer undergoing surgery between January 1978 and
      December 1993, 160 (with 356 neoplastic lesions) had synchronous multiple cancer.
      Of these lesions 271 (76 percent) were early cancers. Only 85 (53 percent) of the
      160 patients were diagnosed before operation as having multiple cancer; 69
      further patients (43 percent) were diagnosed during the course of the operation.
      Small flat (IIb) and depressed (IIc) type lesions had a propensity to be missed
      before operation. The incidence of multiple cancer was relatively low, indicating
      that several microscopic lesions might have been overlooked in this series. There
      has, however, only been one patient (1 percent) with subsequent cancer of the
      gastric remnant of 126 with multiple cancer and postoperative gastric remnants
      over the past 16 years. This might be because of co-resection of unrecognized
      lesions by distal gastrectomy in 68 percent of the patients. Alternatively some
      microscopic cancers might not invariably be destined to grow into clinically
      significant lesions over 10 or more years.

PMID- 8535815
TI  - Laparoscopic management of cholecystoenteric fistula.

PMID- 8535814
TI  - Cystic duct laceration by metallic clips: a cautionary note.

PMID- 8535816
TI  - Treatment of lymphocele in renal transplant recipients by laparoscopic
      fenestration after transcutaneous staining.

PMID- 8535817
TI  - Lothian and Borders large bowel cancer project: immediate outcome after surgery.

PMID- 8535818
TI  - Outcome of patients with abdominal sepsis in an intensive care unit.

PMID- 8535819
TI  - Simplest method of tightening cutting setons.

PMID- 8535820
TI  - Randomized double-blind placebo-controlled trial of early octreotide in patients
      with postoperative enterocutaneous fistula.

PMID- 8535821
TI  - Blood flow in breast cancer and fibroadenoma estimated by colour Doppler
      ultrasonography.

PMID- 8535822
TI  - Octreotide inhibits the growth and development of three types of experimental
      liver metastasis.

PMID- 8535823
TI  - Computed tomographic portography in preoperative imaging of hepatic neoplasm.

PMID- 8535824
TI  - Computed tomography portography in preoperative imaging of hepatic neoplasm.

PMID- 8535825
TI  - 22nd World Congress of the International Society for Cardiovascular Surgery.
      Kyoto, Japan, September 10-14, 1995. Abstracts.

PMID- 8535826
TI  - Correlation of synergistic cytotoxic effects of environmental chemicals in human
      fibroblasts with their lipophilicity.
AB  - The cytotoxic combination effects of 2,4-D with 12 xenobiotics having different
      lipophilicity were investigated in human fibroblasts at their no effect
      concentrations (NOEC). Each of the chemicals tested in binary combinations
      enhanced the toxicity of 2,4-D. These synergistic combination effects were
      independent of the chemical structure of the test compounds. However, the NOEC's
      of the xenobiotics used in the combinations varied by a factor of 10,000. For
      strongly lipophilic compounds the lowest NOEC's were needed to induce synergistic
      cytotoxicity. A linear regression analysis of the concentrations (NOEC's) of the
      12 combined xenobiotics against their lipophilicity revealed a correlation with r
      = 0.96 for 11 agents. This close correlation may be explained by the membrane
      damaging properties of lipophilic compounds which enhance the uptake of
      hydrophilic agents.

PMID- 8535827
TI  - Microbial degradation of di-n butyl phthalate.
AB  - Microorganisms capable of degrading di-n-butyl phthalate (DBP) were isolated. The
      characteristics of DBP biodegradation by immobilized and free cells were
      investigated. The experimental results showed that the rate of DBP degradation of
      immobilized cells was higher than that of free cells.

PMID- 8535828
TI  - PCDD, PCDF, planar and other PCB levels in human milk in Japan. off.
AB  - 26 human milk samples in Japan were individually analyzed for PCDDs, planar and
      other PCB. Mean total concentrations of PCDDs planar and other PCBs were 8.5
      pg/g, 8.8 pg/g and 5.5 ng/g of whole milk, respectively. TEQs were calculated
      using International-TEFs(I-TEFs) for PCDDs/Fs and TEFs proposed by the WHO for
      planar PCBs. Mean total TEQs of PCDDs and planar PCBs were 0.48, 0.63 and 0.39
      pg/g of whole milk, respectively. These values were similar to those of other
      industrialized countries.

PMID- 8535829
TI  - Mass spectral identification of metabolites formed by microbial degradation of
      polycyclic aromatic hydrocarbons (PAH).
AB  - This paper deals with the identification of PAH metabolites, which are formed
      during PAH bioremediation. The investigation was performed with
      trimethylsilylation (TMS) of the sample, following gas chromatographic (GC)
      separation and mass spectrometry (MS). The mass spectra were analysed, rules of
      fragmentation developed and characteristic fragments were presented.

PMID- 8535830
TI  - Comments on the extraction of fat from human milk for analysis of contaminants.

PMID- 8535831
TI  - Inability to restore resting intracellular calcium levels as an early indicator
      of delayed neuronal cell death.
AB  - The hippocampus is especially vulnerable to excitotoxicity and delayed neuronal
      cell death. Chronic elevations in free intracellular calcium concentration
      ([Ca2+]i) following glutamate-induced excitotoxicity have been implicated in
      contributing to delayed neuronal cell death. However, no direct correlation
      between delayed cell death and prolonged increases in [Ca2+]i has been determined
      in mature hippocampal neurons in culture. This investigation was initiated to
      determine the statistical relationship between delayed neuronal cell death and
      prolonged increases in [Ca2+]i in mature hippocampal neurons in culture. Using
      indo-1 confocal fluorescence microscopy, we observed that glutamate induced a
      rapid increase in [Ca2+]i that persisted after the removal of glutamate.
      Following excitotoxic glutamate exposure, neurons exhibited prolonged increases
      in [Ca2+]i, and significant delayed neuronal cell death was observed. The N
      methyl-D-aspartate (NMDA) channel antagonist MK-801 blocked the prolonged
      increases in [Ca2+]i and cell death. Depolarization of neurons with potassium
      chloride (KCl) resulted in increases in [Ca2+]i, but these increases were
      buffered immediately upon removal of the KCl, and no cell death occurred. Linear
      regression analysis revealed a strong correlation (R = 0.973) between glutamate
      induced prolonged increases in [Ca2+]i and delayed cell death. These data suggest
      that excitotoxic glutamate exposure results in an NMDA-induced inability to
      restore resting [Ca2+]i (IRRC) that is a statistically significant indicator of
      delayed neuronal cell death.

PMID- 8535832
TI  - The neurotoxins colchicine and kainic acid block odor-induced fast waves and
      olfactory-evoked potentials in the dentate gyrus of the behaving rat.
AB  - It has previously been shown that the hilus of the dentate gyrus responds to
      odors (e.g. toluene) with a burst of fast waves and to electrical stimulation of
      the olfactory bulb with an evoked potential consisting of an early component
      immediately after the stimulus artifact, a second component with a 16-18-ms
      latency and additional late components. Spectral analysis revealed that odor
      induced fast-wave bursts in the olfactory bulb and dentate gyrus both had a peak
      frequency of 15-20 Hz and were highly coherent. Unilateral intrahippocampal
      injections of colchicine or kainic acid were used in an attempt to destroy
      granule and pyramidal cells, respectively, while saline was injected on the
      opposite side as a control. Recordings from chronically implanted electrodes in
      the olfactory bulb and dentate gyrus demonstrated that saline had no effect while
      either neurotoxin abolished the odor-induced fast waves. In addition, the late 16
      18-ms component of the dentate-evoked potentials after single-pulse stimulation
      of the olfactory bulb was abolished by either kainic acid or colchicine; the
      early dentate response, probably a volume-conducted olfactory response, was not
      abolished. Histological analysis indicated that kainic acid produced widespread
      non-specific damage in the hippocampal formation. Kainic acid-treated tissue
      exhibits a thinning of granule cell and molecular layers of the dentate gyrus as
      well as cell loss in CA3 and part of CA1.

PMID- 8535833
TI  - Release into ventriculo-cisternal perfusate of beta-endorphin- and Met-enkephalin
      immunoreactivity: effects of electrical stimulation in the arcuate nucleus and
      periaqueductal gray of the rat.
AB  - To examine the resting and evoked release of the endogenous opioid peptides beta
      endorphin and Met-enkephalin from brain, we examined the levels of the respective
      immunoreactivities in the lateral ventricle-cisterna magna perfusate of the
      halothane-anesthetized rat. Ten Hz but not 100 Hz stimulation in the arcuate
      nucleus (ARC) of the hypothalamus released beta-endorphin immunoreactivity (beta
      EPir) to the perfusate, whereas 100 Hz but not 10 Hz stimulation in the
      periaqueductal gray (PAG) of the mid brain released Met-enkephalin
      immunoreactivity (MEir). MEir was not released by stimulation in ARC and beta
      EPir was not released by stimulation in PAG. Characterization of the released
      beta-EPir and MEir by high performance liquid chromatography showed that
      authentic beta-endorphin and Met-enkephalin were the major constituents of beta
      EPir and MEir, respectively. Systemic administration of the dopaminergic
      antagonist haloperidol increased plasma, but not perfusate levels of beta-EPir.
      Both the opioid antagonist naloxone and the NMDA antagonist MK-801 failed to
      affect beta-EPir or MEir release. ARC and PAG stimulated inhibited a nociceptive
      reflex (tail-dip in 52.5 degrees C water), and naloxone did not reliably reverse
      this inhibition. These data support the previously suggested possibility of
      opioid mediation of stimulation induced analgesia, although we were unable to
      confirm the theory by naloxone reversibility in this study. Furthermore, the data
      support the assumption that measurement of opioid peptides in cerebrospinal fluid
      is a relevant approach in research aimed at elucidating the physiological and
      pathophysiological roles of endogenous opioid peptides.

PMID- 8535834
TI  - Parafascicular nucleus-raphe projections and termination patterns in the rat.
AB  - Thalamic projections from the parafascicularis nucleus to the raphe system were
      studied by means of anterograde techniques, utilizing both biocytin and dextran
      amine in rats. Both tracers injections in the parafascicularis nucleus resulted
      in the labeling of descending bundles of fibers running along the brainstem.
      Labeled terminal fields were found in all the raphe nuclei except the nucleus
      raphe pallidus. Three different types of labeled terminals (numerous small
      boutons, less numerous large claw-like terminals, varicosities in close
      apposition to blood vessel walls) originating from the parafascicular nucleus
      were present in the raphe system. Ultrastructural data suggest an inhibitory
      nature for the parafascicular-raphe projections. Our results confirm and extend
      previous retrograde data by indicating the trajectories, the terminal fields, the
      fine structure of terminal axonal arborizations and boutons. Based on previous
      retrograde data and our observations, we conclude that the relationship between
      the parafascicular nucleus and raphe system is reciprocal and concerns most of
      the raphe nuclei, suggesting that parafascicularis cell population may be
      involved in many of the functions ascribed to the raphe system.

PMID- 8535835
TI  - Increased neuropeptide Y secretion in the hypothalamic paraventricular nucleus of
      obese (fa/fa) Zucker rats.
AB  - NPY is synthesized in the hypothalamic arcuate nucleus (ARC), and NPY injected
      into the paraventricular nucleus (PVN), the main site of NPY release, induces
      hyperphagia and reduces energy expenditure. Hypothalamic NPY mRNA and NPY levels
      are increased in fatty Zucker rats, consistent with increased NPY release. This
      could explain the hyperphagia and reduced energy expenditure, which lead to
      obesity in the fatty Zucker rat. We have therefore compared NPY secretion in the
      PVN of conscious fatty and lean Zucker rats using push-pull sampling. The NPY
      secretory profile was consistently higher in fatty Zucker rats than in lean rats
      throughout the 3-h study period (P < 0.01), and mean NPY secretion over the whole
      3 h was increased 2-fold in the fatty rats (P < 0.001). We conclude that fatty
      Zucker rats have increased NPY release in the PVN. This observation further
      supports the hypothesis that increased activity of the NPYergic ARC-PVN pathway
      may contribute to obesity in the fatty Zucker syndrome.

PMID- 8535836
TI  - Induction of c-fos protein by patterned visual stimulation in central visual
      pathways of the rat.
AB  - Localized patterned visual stimulation was used in rats to investigate the
      feasibility of stimulus-dependent induction of the immediate early gene c-fos in
      neurons of cortical and subcortical visual centers of this mammal. Moving and
      stationary visual patterns, consisting of gratings and arrays of dark dots,
      induced Fos-like immunoreactivity in populations of neurons in retinotopically
      corresponding stimulated regions of the dorsal and ventral lateral geniculate
      nucleus (dLGN, vLGN), stratum griseum superficiale of the superior colliculus,
      nucleus of the optic tract, and primary (striate) visual cortex. Only moving
      stimuli induced Fos-like immunoreactive (FLI) neurons in extrastriate visual
      areas, particularly in the anterolateral (AL) visual area. This suggests that
      area AL is equivalent to the motion sensitive areas MT and PMLS of the monkey and
      cat. Stimulus-induced FLI neurons in the striate cortex were predominantly
      distributed in layers 4 and 6, while few labeled neurons were present in layers 2
      3, and almost none in layer 5. The laminar distribution of stimulus-induced FLI
      cells in the extrastriate cortical area AL was similar to that of the striate
      cortex, with the exception that more FLI cells were present in layer 5.
      Statistical comparison of somata size of the stimulus-induced FLI neurons in dLGN
      with that of Cresyl violet stained neurons in the same sections revealed that the
      population of geniculate FLI neurons is composed of relay cells and interneurons.

PMID- 8535837
TI  - Involvement of sigma 1 receptor in (+)-N-allylnormetazocine-stimulated
      hippocampal cholinergic functions in rats.
AB  - The effects of the stereoisomers of N-allylnormetazocine (SKF-10,047) on the
      hippocampal cholinergic functions were compared in rats. A putative sigma 1
      receptor agonist, (+)-SKF-10,047, elicited an increase of hippocampal
      extracellular acetylcholine level and anti-amnesic effect against scopolamine
      induced memory dysfunctions in rats. These phenomena were not produced by (-)-SKF
      10,047, and were reversed by haloperidol, a putative sigma 1 receptor antagonist.
      Such stereoselectivity and antagonism imply an involvement of sigma 1 receptors
      in these (+)-SKF-10,047-stimulated hippocampal cholinergic functions.

PMID- 8535838
TI  - Basal release of Met-enkephalin and neurotensin in the ventrolateral
      periaqueductal gray matter of the rat: a microdialysis study of antinociceptive
      circuits.
AB  - The periaqueductal gray (PAG) contains neural circuits that participate in
      descending antinociception. Anatomical and electrophysiological evidence suggests
      that these circuits might employ opioid peptides and GABA in series to remove a
      tonic inhibition of descending PAG output neurons. The present studies examined
      the release of the antinociceptive peptides Met-enkephalin and neurotensin in the
      ventrolateral PAG, and investigated the interaction between GABA and Met
      enkephalin release. In awake and freely moving rats the ventrolateral PAG was
      dialysed using 25 ga. concentric probes. Basal release of peptide in 12 min or 40
      min fractions was determined using radioimmunoassays. To establish how the
      ventrolateral PAG responds to nociception, dialysis was performed following
      unilateral hindpaw inflammation using Complete Freund's Adjuvant. Twenty-four
      hours after inflammation was induced, neurotensin release was increased 133% and
      Met-enkephalin release was increased 353% compared to control animals. Seven days
      after inflammation was induced, neurotensin release declined precipitously, while
      basal Met-enkephalin release remained elevated 313% above controls. Thus, unlike
      enkephalin, increased basal neurotensin release is not sustained with persistent
      tonic nociception. In addition, we confirmed in normal animals that the
      ventrolateral PAG is induced to release Met-enkephalin by systemic morphine. A
      43% increase in basal Met-enkephalin release was observed immediately following a
      12 mg/kg i.p. morphine injection. Morphine should have the opposite effect
      (inhibit peptide release) if it acts directly on the enkephalinergic neurons.
      Thus, we examined the hypothesis that GABAergic interneurons in the PAG mediated
      morphine-stimulated enkephalin release. When the GABAantagonist bicuculline (0.25
      microM to 25 microM) was co-infused with the dialysis medium, Met-enkephalin
      release increased in a dose-dependent fashion and peaked 68% above pre-infusion
      levels. These data elucidate the reciprocal inhibitory relationship between GABA
      and enkephalin in the ventrolateral PAG. We hypothesize that, when nociception
      induces Met-enkephalin release within this region, the tonic GABAergic inhibition
      is overcome, resulting in greater sensitivity of PAG enkephalinergic neurons.
      Ultimately, this enhanced enkephalin release should result in greater
      excitability of the descending PAG output neurons that are responsible for
      antinociception.

PMID- 8535839
TI  - Localization and quantification of the dopamine transporter: comparison of
      [3H]WIN 35,428 and [125I]RTI-55.
AB  - Transport into the presynaptic terminal by the dopamine transporter is the
      primary mechanism for removing dopamine from the synaptic cleft. This transporter
      is a specific marker for dopamine terminals and is a primary site for CNS actions
      of cocaine. Several radioligands have been developed for analysis of the dopamine
      transporter. The ligands vary in affinity and specificity, leading to differences
      in reported transporter density in brain regions. We compared two of the most
      commonly used ligands, [3H]WIN 35,428 and [125I]RTI-55, analyzing the
      localization and density of sites in the rat brain using serial sections and
      quantitative autoradiography. Citalopram at 50 nmol/l was used to block [125I]RTI
      55 binding to serotonin transport sites. Transporter density was highest in the
      striatum and both ligands labeled equivalent numbers of sites, with lateral to
      medial and anterior to posterior gradients. In most areas the density of sites
      measured with the two ligands was similar. However, [125I]RTI-55 binding was
      significantly higher than [3H]WIN 35,428 binding in the substantia nigra zona
      compacta, ventral tegmental area, subthalamic nucleus and a number of other
      subcortical nuclear groups while [3H]WIN 35,428 binding was higher in lateral
      striatum and in olfactory tubercle. These differences could reflect different
      forms of the transporter, perhaps due to post-translational modifications, and
      they may provide a basis for differential pharmacological regulation of
      transporter function in discrete brain regions and disease states.

PMID- 8535840
TI  - Enkephalin-immunoreactive fastigial neurons in the rat cerebellum project to
      upper cervical cord segments.
AB  - By using enkephalin immunohistochemistry combined with retrograde fluorescent
      labelling, a great majority of neurons in the rat cerebellum sending their axons
      to the spinal cord were shown to contain enkephalin immunoreactivity. These
      neurons were numerous and clustered in the fastigial nucleus but far less
      abundant in other cerebellar nuclei. Enkephalin-immunoreactive fibers present in
      the ventral horn and the central cervical nucleus of upper cervical cord segments
      almost completely disappeared contralaterally following kainic acid-induced cell
      loss in the fastigial nucleus. The results indicate that fastigial and some other
      cerebellar nucleus neurons provide enkephalin-containing projections toward these
      spinal sites.

PMID- 8535841
TI  - Localization of NADPH-diaphorase/nitric oxide synthase in the rat retina: an
      electron microscopic study.
AB  - The activity of NADPH-diaphorase (NADPH-d), a marker for nitric oxide synthase
      (NOS), was examined histochemically in the rat and mice retina. Mice in which the
      neuronal NOS gene has been disrupted (nNOS- mice) were used for specificity
      controls. Light microscopically a few amacrine cells were heavily stained. Other
      cells were stained weakly or not at all. Under the electron microscope, formazan
      precipitates were detectable on membranes of endoplasmic reticulum, nuclear
      envelope, mitochondria, and, in a few cases, the Golgi complex. Bipolar,
      horizontal, and Muller cells, were if at all, sparsely labeled with formazan.
      Labeled mitochondria were observed in rod endings and in inner segments of
      photoreceptors. Outer segments of photoreceptors and ganglion cells were
      completely free of reaction product. The NADPH-d reaction in wild-type mice
      displayed a similar distribution pattern to that in rats. Retinae of nNOS- mice
      showed a complete lack of prominent NADPH-d stained (amacrine) cells. None or a
      very few labeled membranes were seen.

PMID- 8535842
TI  - Immunohistochemical evidence for enkephalin and neuropeptide Y in rat inferior
      colliculus neurons that provide ascending or commissural fibers.
AB  - Enkephalin- and neuropeptide Y-expressing neurons which offer commissural axons
      or axons toward auditory thalamus were identified in the rat inferior colliculus.
      These neurons exhibited a differential distribution pattern. The results provide
      evidence for regional specificity and chemical heterogeneity of neurons in the
      auditory midbrain.

PMID- 8535843
TI  - An anti-tumor necrosis factor antibody suppresses sleep in rats and rabbits.
AB  - It is hypothesized that tumor necrosis factor (TNF) is an endogenous sleep
      promoting substance. In the present experiments we studied the effects of a
      monoclonal anti-TNF antibody in rats and rabbits. Seven rats and 14 rabbits were
      implanted with electroencephalographic electrodes, a brain thermistor and an
      intracerebroventricular guide cannula. The animals were injected with saline,
      control IgG, and monoclonal hamster anti-murine-TNF antibodies (TNFab) on 3
      separate days. Ten micrograms TNFab suppressed non-rapid-eye-movement sleep
      (NREMS) in rats. In rabbits, 2.5 micrograms TNFab did not affect sleep but
      decreased brain temperature; in contrast, 25 micrograms TNFab suppressed NREMS
      without affecting brain temperature. These results are consistent with the
      hypothesis that endogenous TNF plays an important role in sleep regulation.

PMID- 8535844
TI  - Prenatal exposure to morphine alters brain mu opioid receptor characteristics in
      rats.
AB  - Prenatal morphine exposure alters neither the binding capacity nor the affinity
      of ligand binding to mu opioid receptors of adult male brains. However, males
      have significantly higher Bmax in the hypothalamus than ovariectomized females.
      In females, prenatal exposure to morphine reduces the Bmax of mu opioid receptors
      25% in the hypothalamus and preoptic area. Estrogen treatment increases the Bmax
      of mu opioid receptors in the striatum of all ovariectomized females but in the
      hypothalamus only of morphine-exposed females, thereby eliminating the sex
      difference observed in control animals.

PMID- 8535845
TI  - Calcitonin gene-related peptide (CGRP) content and CGRP receptor binding sites in
      discrete forebrain regions of alcohol-preferring vs. -nonpreferring rats, and
      high alcohol-drinking vs. low alcohol-drinking rats.
AB  - This study showed that alcohol-preferring (P) rats and high alcohol-drinking
      (HAD) rats possess fewer calcitonin gene-related peptide (CGRP) receptor binding
      sites than their respective controls in the central amygdaloid nucleus (CeA)
      which is known to be related to anxiety. Since P and HAD rats are selectively
      bred for high alcohol preference, and alcohol can produce anxiolytic effect, one
      can postulate that P and HAD rats preferentially drink alcohol in order to obtain
      its anxiolytic effect. This study supports a hypothesis that deficit of CGRP
      receptors in the CeA of P and HAD rats may contribute to alcohol preference.

PMID- 8535846
TI  - Non-photic manipulations induce expression of Fos protein in the suprachiasmatic
      nucleus and intergeniculate leaflet in the rat.
AB  - Expression of Fos protein in the suprachiasmatic nucleus (SCN) and
      intergeniculate leaflet (IGL) is considered a cellular correlate of light-induced
      phase-shift of circadian rhythms in rodents. Non-photic stimuli also induce phase
      shifts, but their effects on Fos expression have not been established. We
      examined induction of Fos protein in SCN and IGL regions, in response to cage
      change, intraperitoneal saline injection, and restraint stress. Fos
      immunoreactivity was observed in SCN and IGL regions, with greater expression
      observed in IGL during the light phase of the light-dark cycle. Results suggest
      that cells in SCN and IGL respond to several types of non-photic manipulations
      and that expression of Fos in these regions is not light-specific.

PMID- 8535847
TI  - GBR-12909-induced self-injurious behavior: role of dopamine.
AB  - A regimen of repeated administration of GBR (10 or 20 mg/kg/day, i.p., for 4
      days) to female Sprague-Dawley rats induced a dose-and time-related increase in
      the incidence of self-injurious behavior (SIB) that consisted of injury to body
      areas, paws and tail. The treatment regimen decreased striatal DA and DOPAC
      levels. Dopaminergic denervation with 6-hydroxydopamine (6-OHDA) or D1 DA
      antagonist, SCH-23390 or D2 DA antagonist, spiperone, blocked the GBR-induced
      SIB. Male rats were less sensitive than female rats to exhibit a comparable
      incidence of SIB. Taken together, the study reveals that repeated administration
      of GBR induces SIB that is dependent on the integrity of nigrostriatal
      dopaminergic system and the presence of D1 and/or D2 DA receptors.

PMID- 8535848
TI  - Presynaptic D2 dopaminergic receptors mediate inhibition of excitatory synaptic
      transmission in rat neostriatum.
AB  - The effect of dopamine (DA) on excitatory synaptic transmission was studied in
      rat neostriatal neurons using intracellular- and whole-cell voltage clamp
      recording methods. Depolarizing excitatory postsynaptic potentials (EPSPs) were
      evoked by cortical stimulation. Superfusion of DA (0.01-10 microM) reversibly
      decreases EPSP in a concentration-dependent manner and with a estimated IC50 of
      0.3 microM. In addition, the inhibitory effect induced by DA at a low
      concentration (0.1 microM) was antagonized by sulpiride (1-10 nM), a selective D2
      dopaminergic receptor antagonist. However, D1 dopaminergic receptor antagonist
      SKF-83566 (1-5 microM) did not affect the blocking effect by DA 0.1 microM. Based
      on these findings, we conclude that DA at a low concentration (< or = 0.1 microM)
      reduced the excitatory response of neostriatal neurons following cortical
      stimulation via the activation of D2, but not D1 dopaminergic receptors, located
      on the terminals of corticostriatal neurons.

PMID- 8535849
TI  - Astrocytic volume fluctuates in the hippocampal CA1 region across the estrous
      cycle.
AB  - The number of dendritic spine synapses in the hippocampal CA1 stratum radiatum
      fluctuates across the rat estrous cycle, being high on proestrus and low on
      estrus [20]. We hypothesized that the volume occupied by astrocytic processes
      changes in a complementary manner. The volume fraction of astrocytic processes
      was determined stereologically in CA1 s. radiatum and s. lacunosum-moleculare of
      cycling female rats. Consistent with our hypothesis, the volume fraction was
      significantly lower on the afternoon of proestrus than on the afternoon of estrus
      in both laminae.

PMID- 8535850
TI  - Evidence of a physiological role for neuropeptide Y in ventromedial hypothalamic
      lesion-induced hyperphagia.
AB  - We evaluated the role of neuropeptide Y (NPY), a potent endogenous orexigenic
      signal, in the ventromedial hypothalamic (VMH) lesion-induced hyperphagia in
      rats. To produce hyperphagia and excessive weight gain, adult female rats
      received bilateral electrolytic or sham lesions in the VMH. Concurrently, a
      permanent intracerebroventricular cannula was implanted in the third ventricle of
      the brain. After a recovery period, these rats were passively immunized against
      NPY to evaluate the role of endogenous NPY on hyperphagia. The results showed
      that intraventricular administration of NPY antibodies abolished the hyperphagia
      in VMH-lesioned rats. These revelations are in agreement with the notion that
      altered hypothalamic NPY release or action may underlie the hyperphagia and
      excessive weight gain seen in response to structural damage in the VMH.

PMID- 8535851
TI  - Depletion of NOS activity in the rat dentate gyrus neurons by DSP-4 and
      protection by deprenyl.
AB  - DSP-4 is a potent and highly selective neurotoxin of noradrenergic axons of locus
      coeruleus origin. The authors found that in addition to depletion of the
      hippocampal noradrenergic terminals the histochemical reactivity of nitric oxide
      synthase (NOS, NADPH-diaphorase) was lost from neurons in the subgranule zone and
      hilar region of the dentate gyrus 2 weeks after a systemic administration of this
      toxin. Pretreatment with R(-)-deprenyl and 2-HxMP (2-hexyl-N
      methylpropargylamine, which protects hippocampal noradrenergic axons against DSP
      4 neurotoxicity, led to a complete prevention of the loss of NADPH-diaphorase
      activity.

PMID- 8535852
TI  - Differential effects of unilateral lesions in the medial amygdala on spontaneous
      and induced ovulation.
AB  - The possible existence of asymmetry in the control of ovulation by the medial
      amygdala was explored. Unilateral lesions of the medial amygdala were performed
      on each day of the estrous cycle. The estral index diminished in almost all
      animals with a lesion in the right side of medial amygdala. Lesions of the right
      medial amygdala, when performed on diestrus-1, resulted in a significant decrease
      in the number of rats ovulating compared to controls (4/8 vs. 8/8, p < 0.05). In
      ovulating animals a significant reduction in the number of ova shed by the left
      ovary was found (2.2 +/- 0.8 vs. 6.3 +/- 0.8, p < 0.05). Lesions of the stria
      terminalis performed on diestrus-1 did not affect ovulation. In a second
      experiment, administration of GnRH did not restore ovulation in rats with lesions
      of the right medial amygdala. However, sequential injections of PMSG-hCG did
      result in ovulation by all members of a group of lesioned animals. In this last
      condition a significant decrease in the number of ova shed by the right ovary was
      found compared to animals in the lesion-only condition (1.5 +/- 0.5 vs. 6.0 +/-
      1.5, p < 0.05). These data suggest that control of ovulation by the medial
      amygdala is asymmetric and varies during the estrous cycle.

PMID- 8535853
TI  - An electrophysiological study on the vagal innervation of the thymus in the rat.
AB  - Vagal innervation of the thymus was studied by means of electrophysiological
      technique in the rat. Under urethane anesthesia, evoked action potentials
      originated from cervical vagus by electrical stimulations were recorded from the
      central cut end of the thymic branch of the vagus nerve after averaging for 32
      times. It was observed that the conduction velocities are distributed in the
      range of 0.56-6.84 m/s, and the majority of vagal fibers in the thymic branch of
      the vagus nerve belong to a nonmyelinated C-fiber group. Further, it was
      confirmed that the right and left lobes of the thymus are innervated by cervical
      vagi bilaterally. The results suggest that the thymic branch of the vagus nerve
      plays a role in modulation of thymic function.

PMID- 8535854
TI  - Modulation of metabolic effects of morphine-6-glucuronide by morphine-3
      glucuronide.
AB  - Modification of pharmacological effects of morphine by its glucuronides has been
      recently reported. Morphine-6-glucuronide (M6G) is a more potent opioid agonist
      than morphine, whereas morphine-3-glucuronide (M3G) has no opioid effects and has
      been suggested to be an antagonist of morphine's antinociceptive and respiratory
      depressive effects. This study addressed the metabolic effects of direct central
      nervous system administration of M3G and its interaction with the hyperglycemic
      effects of M6G. Hormonal and whole body glucose metabolic effects of M3G, M6G,
      and M3G + M6G ICV administration were studied in conscious unrestrained
      chronically catheterized rats. Whole body glucose kinetics were assessed with a
      primed constant intravenous infusion of 3[3H]glucose in rats injected
      intracerebroventricularly (ICV) with H2O (5 microliters), M3G (1 microgram), M6G
      (1 microgram), or M3G (1 microgram) + M6G (1 microgram). A significant rise in
      plasma glucose level was observed after ICV injection of M6G (28%), and M3G + M6G
      (41%), but not after M3G as compared to time-matched H2O control. Early increases
      in the rate of glucose appearance (Ra) and whole body glucose utilization (Rd)
      were observed (58% and 48%, respectively) 30 min after M3G + M6G administration,
      whereas the increases after M6G injection were progressive and reached values 47%
      higher than basal 180 min after injection. M3G administration enhanced the M6G
      induced increase in plasma glucose level (+21%), Ra (+29%), Rd (+26%), and plasma
      lactate level (+21%). Though no significant hormonal change was observed in H2O,
      M3G, and M6G injected animals, the combination of M3G + M6G resulted in a
      significant increase in circulating catecholamine levels with no alterations in
      plasma corticosterone, insulin, and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535855
TI  - Centrally infused anions alter body temperature in conscious rats.
AB  - Central anionic influences on the regulation of body temperature were studied in
      42 conscious male rats. The animals were divided into seven equal groups and were
      given intraventricular infusions of either chloride or bicarbonate solution of
      sodium, calcium, or potassium. Infusions were made in the unanesthetized and
      unrestrained animals through stainless steel cannulae, chronically implanted into
      the anteroventral part of third ventricle. Control rats received intraventricular
      infusions of artificial cerebrospinal fluid. All of the chloride solutions,
      irrespective of the associated cations, elicited hyperthermia, whereas
      bicarbonates had hypothermic effect. Responses of chloride and bicarbonate
      solutions varied significantly (p < 0.001). There was, however, cationic
      modification of the anionic responses. Thus, sodium ions manifested hyperthermic
      modifications, accentuating hyperthermia of chloride and attenuating hypothermic
      effect of bicarbonate. Calcium and potassium ions exerted hypothermic modulation.
      The results suggest that anionic concentration of intraventricular CSF is crucial
      for central regulation of body temperature in unanesthetized conscious rats. The
      cations probably have only modulatory influences.

PMID- 8535856
TI  - Orienting-related eye-neck neurons of the medial ponto-bulbar reticular formation
      do not participate in horizontal canal-dependent vestibular reflexes of alert
      cats.
AB  - Ponto-bulbar reticular formation neurons, including identified reticulospinal
      neurons, were studied in alert, head-fixed cats. Orienting-related neurons of
      "eye-neck" type (ENNs) were selected on the basis of qualitative correlations of
      their discharges with visually triggered eye saccades and electromyographic
      activity (EMG) of dorsal neck muscles. It was tested whether ENNs participate
      both in visually triggered gaze shifts requiring eye-head coordination and in
      gaze-stabilizing movements, such as vestibulo-ocular and vestibulo-collic
      reflexes (VOR, VCR). Firing patterns were studied during passive sinusoidal
      rotation (0.2-1.0 Hz; 2.0-21.5 deg peak-to-peak) in the horizontal plane.
      Responses to electrical stimulation of the superior colliculus and the vestibular
      nerve were recorded to assess the convergence of tectal and vestibular synaptic
      inputs. The same methods were applied to a control sample of neurons with
      discharges apparently "unrelated" to orienting movements. ENNs did not show any
      modulation of firing rate correlated to compensatory VOR or VCR during passive
      sinusoidal rotations. Among "unrelated" cells, the fraction of modulated units
      was close to that reported for reticular neurons projecting in the medial
      reticulospinal tract. Phasic and sustained components of ENN bursts were
      associated with anticompensatory movements induced by rotation, such as quick
      phases, ocular beating field shift, and the increase of EMG activity in neck
      muscles acting in the direction of passive rotation. Monosynaptic excitation from
      the contralateral superior colliculus was observed in 92.3% of ENNs, but only 2
      out of 17 tested showed an excitatory response to vestibular nerve stimulation.
      In the control group of "unrelated" neurons the proportions of monosynaptic
      tectal and excitatory vestibular nerve inputs were, respectively, 75.6 and 71.4%.
      It is concluded that ENNs are specifically related to active gaze shifts, derived
      from either visual or from head velocity inputs. Rhombencephalic connections of
      vestibular nuclei to these neurons appear to be quite weak. Parallel inputs from
      the mid- or forebrain must be assumed to explain their firing patterns during
      rotation-induced anticompensatory gaze shifts. Within the studied range of
      frequencies and amplitudes of passive rotation, ENNs did not participate in the
      vestibulo-collic reflex. It is therefore unlikely that reticular neurons
      controlling orienting eye-neck synergies act also as a premotor pathway for gaze
      stabilizing movements.

PMID- 8535857
TI  - Retrograde labeling of retinal ganglion cells and brain neuronal subsets by [3H]
      D-aspartate injection in the Syrian hamster hypothalamus.
AB  - The circadian pacemaker in the suprachiasmatic nuclei (SCN) is entrained to the
      environmental light-dark cycle via a direct retinal projection to the
      hypothalamus. This projection is thought to use glutamate or aspartate as
      neurotransmitter. [3H]-D-Aspartate was microinjected in the SCN and adjacent
      hypothalamic nuclei of Syrian hamsters. This neuronal tracer is selectively taken
      up by terminals of neurons that use glutamate or aspartate as neurotransmitter
      and retrogradely transported to their perikarya. With autoradiography labeled
      cells were visualized in the retinal ganglion cell layer. Labeled cells were also
      found in a subset of brain nuclei known to project to the injection area. Labeled
      cells were detected in the bed nucleus of the stria terminalis, paraventricular
      nucleus of the thalamus, lateral septal nucleus, and medial amygdaloid nucleus.
      No labeled cells were observed in the medial septal nucleus, intergeniculate
      leaflet, and ventral lateral geniculate nucleus, which are also known to project
      to the SCN. Our results indicate that glutamatergic/aspartatergic retinal
      ganglion cells project to the SCN and adjacent medial hypothalamic nuclei.
      Moreover, the SCN may receive glutamatergic/aspartatergic input from the brain
      neuronal subsets that were retrogradely labeled with [3H]-D-aspartate.

PMID- 8535858
TI  - Effects of chronic naloxone administration on vacuous chewing movements and
      catalepsy in rats treated with long-term haloperidol decanoate.
AB  - Most antipsychotic medications produce motoric side effects, including
      parkinsonism and tardive dyskinesia (TD). Correlates of these behaviors in rats
      (catalepsy and vacuous chewing movements, respectively) were used as a model to
      assess the usefulness of chronic naloxone administration in symptom reduction.
      Previous studies have suggested that increased neurotransmission in the
      endogenous opioid system modulates neuroleptic-induced motoric side effects. Rats
      were treated with haloperidol decanoate or vehicle for 27 weeks, and withdrawn
      for 30 weeks. Subsequently, naloxone (0.5 to 2.0 mg/kg SC twice daily) was given
      for 5 weeks. Long-term haloperidol treatment produced a syndrome of vacuous
      chewing movements (VCMs) that persisted during the drug withdrawal period.
      Catalepsy developed rapidly and also persisted. Naloxone treatment had little
      effect on VCMs but increased catalepsy scores in both haloperidol and vehicle
      treated groups. Naloxone reduced rearing and grooming in haloperidol rats while
      increasing these measures in vehicle treated rats. The results indicate that
      neuroleptic-induced motoric side effects are not reversed by naloxone in rats.
      Furthermore, they suggest that increased opioid neurotransmission may not
      underlie the expression of VCMs. This does not rule out the possibility that
      endogenous opioid system may be involved in the development of VCMs. To the
      extent that this animal model is valid, naloxone may not be effective in treating
      TD and neuroleptic-induced parkinsonism in humans.

PMID- 8535859
TI  - Regional differences in cerebral vasomotor control by nitric oxide.
AB  - Regional differences in the role of nitric oxide in cerebral vasomotor control
      were investigated with a nitric oxide synthesis inhibitor, NG-monomethyl-L
      arginine, or a precursor of nitric oxide, L-arginine using both dog cerebral
      angiography for the larger artery study and rat isolated arterioles for the
      microcirculation study. NG-monomethyl-L-arginine (10 mumol) constricted the dog
      cerebral arteries, by 15.6%, 17.5%, and 27.3% in the middle cerebral, anterior
      cerebral, and basilar arteries, respectively. The greater constriction of the
      basilar artery did not reach statistical significance. However, L-arginine (100
      mumol) produced significantly greater dilation of basilar arteries than the
      middle cerebral or anterior cerebral (31.3% vs. 16.7% or 13.1%). NG-monomethyl-L
      arginine at 10(-3) M constricted rat arterioles originating from basilar arteries
      significantly more than the middle cerebral arteries (23% vs. 14%). L-arginine at
      10(-3) M dilated rat arterioles from basilar arteries significantly more than
      from the middle cerebral artery (24 vs. 11%). These findings suggest that the
      roles of nitric oxide in vasomotor control differs by region in the brain, and it
      may be greater in vessels of the posterior than of the anterior circulation.

PMID- 8535860
TI  - 192IGG-saporin-induced selective lesion of cholinergic basal forebrain system:
      neurochemical effects on cholinergic neurotransmission in rat cerebral cortex and
      hippocampus.
AB  - A novel cholinergic immunotoxin (conjugate of the monoclonal antibody 192IgG
      against the low-affinity nerve growth factor receptor with the cytotoxin saporin)
      producing selective lesions of cholinergic neurons in rat basal forebrain was
      applied to study its effect on hippocampal and cerebral cortical cholinergic
      neurotransmission. Intracerebroventricular injection of 4 micrograms 192IgG
      saporin conjugate resulted in a selective loss of cholinergic cells in the basal
      forebrain nuclei 1 week after application, which was accompanied by decreased
      activities of choline acetyltransferase and by reduced high-affinity uptake of
      [3H]choline into cholinergic nerve terminals in the cerebral cortex and
      hippocampus, as well as by a significant activation of micro- and to a lesser
      extent of astroglial cells in the hippocampus, but hardly in the cerebral
      cortex.. The K(+)-stimulated release of [3H]acetylcholine from cortical and
      hippocampal slices of immunolesioned rats was found to be markedly decreased 1
      week after injection. Cholinergic immunolesion led to enhanced cortical M1
      muscarinic acetylcholine receptor numbers, but did not alter muscarinic receptor
      sensitivity as measured by carbachol-stimulated inositol phosphate production or
      phorbol ester binding to membrane-bound protein kinase C. In the hippocampal
      formation differential enhancements in binding levels of M1-muscarinic
      cholinergic receptor sites in the CA1 region and in the dentate gyrus were
      observed, whereas the nicotinic and M2-muscarinic receptor subtype are seemingly
      not affected by the immunotoxin in either of the subfields studied. Cholinergic
      immunolesioning did not result in any alterations in the hybridization signals
      for m1 through m4 muscarinic acetylcholine receptor mRNA in any region or layer
      of the hippocampus. The data suggest that (i) the novel cholinergic immunotoxin
      192IgG-saporin is an appropriate tool to mimic cholinergic hypofunction in the
      hippocampal formation and cerebral cortex, and (ii) selective and specific
      immunolesion of cholinergic cells in medial septal nuclei differentially affects
      cholinergic receptors in particular hippocampal subfields.

PMID- 8535861
TI  - Microglial chimaerism in human xenografts to the rat brain.
AB  - Neural tissue from human fetuses is currently used for intracerebral
      transplantation to treat patients with Parkinson's disease. The development of
      the human fetal tissue following grafting has been considered mostly, up to now,
      from the neuronal point of view in xenografts. Very little is known, in contrast,
      about nonneuronal, glial, or vascular cells in the grafts. Comparison of the data
      gathered on the development of grafted human neurons with those obtained in
      comparable studies using rat transplants has demonstrated species-specific
      features. We have therefore undertaken a series of studies dealing with
      nonneuronal cells in human-to-rat transplants to reveal other possible species
      specificity of the human tissue. This study has, accordingly, been devoted to the
      immunohistochemical analysis of microglia of host and donor origins in a human to
      rat xenograft paradigm allowing clear distinction of the origin of the cells.
      Human neural tissue was transplanted as a cell suspension into the thalamus of
      adult rats. Amoeboid human microglia were observed in 1-, 2-, and 3-month-old
      transplants, but their density, already relatively low at the first stage,
      decreased further over time. Ramified human microglia were only occasional. In
      sharp contrast, host rat microglia rapidly invaded the transplant in the absence
      of any sign of necrosis. The rat cells exhibited first an amoeboid morphology but
      progressed at the later stages toward a more mature, ramified morphology. These
      results indicate that donor microglia are quite few in number at first and, at
      least, do not proliferate actively after transplantation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8535862
TI  - Roles of dopamine D1 receptors in striatal fos protein induction associated with
      methamphetamine behavioral sensitization in rats.
AB  - To elucidate the roles of dopamine D1 and D2 receptors in mediating strial Fos
      protein induction and behavioral sensitization after methamphetamine
      administration, we examined the effects of the D1 receptor antagonist SCH 23390
      and D2 receptor antagonist sulpiride on these phenomena in rats. Intraperitoneal
      administration of 5.0 mg/kg methamphetamine produced a significant increase in
      Fos-immunoreactive cells in the medial striatum. Prior exposure to 5.0 mg/kg
      methamphetamine enhanced ipsilateral rotational behavior in response to
      subsequent methamphetamine administration in unilateral nigral-lesioned rats
      (sensitization). Pretreatment with SCH 23390 (0.32 mg/kg IP) suppressed
      significantly the expression of striatal Fos protein and the development of acute
      behavioral sensitization following a single injection of 5.0 mg/kg
      methamphetamine. Sulpiride (50 mg/kg IP) was also effective in suppressing
      methamphetamine behavioral sensitization, but did not affect the striatal Fos
      induction. These results suggest that dopamine D1 receptor-mediated mechanisms
      are involved in the striatal Fos protein induction associated with behavioral
      sensitization following exposure to methamphetamine.

PMID- 8535863
TI  - Participation of the central noradrenergic system in the reestablishment of
      copulatory behavior of sexually exhausted rats by yohimbine, naloxone, and 8-OH
      DPAT.
AB  - This study analyzes the impact of a neurotoxic lesion of the central
      noradrenergic system on the pharmacological reversal of the sexual inhibition
      present at sexual exhaustion, by IP treatment with yohimbine (2 mg/kg), 8-hydroxy
      2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.25 mg/kg), and naloxone (3 mg/kg).
      All drugs, at the doses tested, were able to increase the percentage of sexually
      exhausted intact rats showing copulatory behavior 24 h after a sexual satiation
      session. In N-(2-chloroethyl)-N-ethyl-2-2-bromobenzylamine (DSP4)-lesioned,
      sexually exhausted animals, naloxone and 8-OH-DPAT lost their stimulatory effect
      on sexual behavior; yohimbine treatment was still able to markedly increase the
      percentage of satiated rats mounting, intromitting, and exhibiting the
      ejaculatory motor pattern, but inhibited seminal emission. The data strongly
      suggest that the integrity of the central noradrenergic system is essential for
      the pharmacological reestablishment of copulatory behavior in sexually exhausted
      rats. Results are in line with previous data showing that the sexual behavioral
      variables more directly addressing motivational components are severely affected
      by sexual satiation.

PMID- 8535864
TI  - Neuroprotection by MK-801 in temperature maintained gerbils.
AB  - Hypothermia reduces ischemic brain damage, confounding interpretation of the
      neuroprotective effects of drugs. Specifically, the neuroprotectant MK-801 has
      been shown to cause hypothermia. Some have claimed that when body temperature is
      maintained, MK-801 is not a neuroprotectant, whereas others claim it retains its
      neuroprotective activity. MK-801 was evaluated for neuroprotective properties in
      free-regulating as well as temperature-maintained gerbils receiving 5 or 10 min
      of bilateral carotid occlusion. After 10 min of ischemia, free-regulating animals
      exhibited significant hypothermia (as low as 32 degrees C) and showed significant
      neuroprotection after 3 mg/kg IP MK-801. When a hyperthermic body temperature
      (38.5 degrees C) was maintained, no reduction in brain damage was evident after
      up to 10 mg/kg IP MK-801, even when occlusion time was reduced to 5 min. However,
      when a normothermic body temperature (36.5 degrees C) was maintained, 10 mg/kg IP
      MK-801 significantly reduced brain damage after 5 min of ischemia. Thus, although
      a higher dose of the drug is required, MK-801 can reduce ischemic brain damage in
      the absence of hypothermia. The need for this high dose suggests that mechanisms
      other than NMDA receptor complex antagonism may be involved in the
      neuroprotective actions of MK-801.

PMID- 8535865
TI  - World Congress on Inflammation. Brighton, United Kingdom, 17-22 September 1995.
      Abstracts.

PMID- 8535866
TI  - Surfactant apoprotein B deficiency.

PMID- 8535867
TI  - Neurodevelopmental outcome of preterm infants with bronchopulmonary dysplasia.
AB  - The neurodevelopmental outcome of 78 infants with bronchopulmonary dysplasia
      (BPD) was compared with that of 78 control infants matched for birthweight. To
      determine the effect of the severity of BPD, 62 infants requiring oxygen at 36
      weeks' postmenstrual age (sBPD) were compared with their matched controls.
      Infants were followed up to 2 years of age, corrected for prematurity, and were
      classified for neurological impairment, developmental delay, and
      neurodevelopmental disability. Seventy six (98%) BPD infants and 71 (91%)
      controls had follow up data available to two years. Neurological impairment,
      developmental delay, and neurodevelopmental disability occurred more frequently
      in infants with BPD than in controls but this was not significant. For infants
      with sBPD, the increased incidence of neurological impairment and definite
      developmental delay was not significant when compared with the controls, though
      neurodevelopmental disability occurred more frequently (odds ratio (OR) 3.6: 95%
      confidence intervals (CI) 1.1-11.8). Predictors of disability in infants with
      sBPD included periventricular haemorrhage (OR 19.4: 95% CI 4.3-86.6), ventricular
      dilatation (OR 12.8: 95% CI 2.9-57.3), and sepsis (OR 5.0: 95% CI 1.3-19.4).
      Adjusting for the presence of these factors, the association between BPD and
      disability was no longer apparent (OR 0.9: 95% CI 0.2-3.6). The findings suggest
      that BPD is not independently associated with adverse neurodevelopmental outcome.

PMID- 8535868
TI  - Parental factors in cognitive outcome of non-handicapped low birthweight infants.
AB  - A population based cohort of 144 children weighing less than 2000 g who were
      without major handicap, and a random control sample of 163 children born at term
      and weighing over 3000 g were investigated. The aim was to assess the relative
      importance for cognitive development at 5 years of age, of birthweight, parental
      demographic factors, and factors related to the environment in which the child
      was reared. The mean non-verbal IQ was 6.1 points lower (95% CI, 2.3 to 10) for
      the low birthweight (LBW) group, but the difference was reduced to 4.8 points
      (95% CI, 1.1 to 8.5) after adjusting for confounding parental demographic and
      childrearing factors. The verbal IQ was similar for the two groups after such
      adjustment. Paternal education was the main confounding variable, and demographic
      factors such as parental education and family income were much stronger
      predictors of child IQ than birthweight or factors related to the childrearing
      environment. There was no evidence that the cognitive development of low
      birthweight children was more sensitive to a non-optimal childrearing environment
      than that of normal birthweight children. These findings indicate that the risk
      of impaired cognitive development increases with decreasing socioeconomic status,
      and that this risk is much larger than, and independent of, the small risk
      attributable to low birthweight.

PMID- 8535869
TI  - Neurosensory outcome at 5 years and extremely low birthweight. The Victorian
      Infant Collaborative Study Group.
AB  - OBJECTIVE: To establish the stability of neurosensory outcome at 5 years of age
      compared with 2 years of age, and to determine whether the improving survival
      rate of extremely low birthweight (ELBW) (500-999 g) children has been
      accompanied by an increase in the number of severely impaired and disabled
      children in the community. METHODS: A geographically determined cohort study was
      made of consecutive ELBW survivors born in the state of Victoria during 1985-7,
      and during 1979-80, inclusive. Rates of neurosensory impairments and disabilities
      at 2 and 5 or more years of age were measured. RESULTS: Of 212 children surviving
      to 5 years of age born during 1985-7, 211 (99.5%) had been assessed at 2 years of
      age, and 209 (98.6%) were assessed at 5 or more years of age. Of the 208 children
      seen at both 2 and 5 years, 32 children had deteriorated, 23 children had
      improved, and 153 were unchanged, compared with their 2 year assessment. The
      major reason for a change in classification was an alteration in psychological
      test results. Compared with ELBW children born in 1979-80, those born in 1985-7
      had significant reductions in hearing and intellectual impairment. The rate of
      severe neurosensory disability in the 1985-7 cohort was 5.7% compared with 12.4%
      in children born in 1979-80. CONCLUSIONS: The age of 2 is too early to be sure of
      neurosensory outcome in ELBW infants. The additional survivors born in the mid
      1980s, compared with the late 1970s, are free of severe neurosensory disability
      at 5 years of age, with no increase in the absolute number of ELBW children
      surviving with severe neurosensory disability.

PMID- 8535870
TI  - Respiratory illness in families of preterm infants with chronic lung disease.
AB  - AIMS--To examine the relation, based on two types of questionnaires, between (1)
      chronic lung disease of the newborn (CLDN) and lower respiratory illness (LRI) in
      siblings, and between (2) CLDN and asthma, chronic obstruction pulmonary disease
      (COPD), or allergy in parents and grandparents. METHODS--Data from 209 children
      born before 32 weeks of gestation were randomly taken from the records of three
      neonatal units. Taking into account age and gender, the excess of LRI was
      calculated for each family compared with the average of all families.
      Subsequently whether CLDN was associated with an excess of LRI in the family was
      tested. RESULTS--Thirty one (14.8%) children were diagnosed as having CLDN. The
      family probability index for LRI did not differ between children with or without
      CLDN. The prevalence of COPD, asthma, and allergy in parents of children with
      CLDN was similar to that of children without CLDN. The prevalence of LRI was
      18.1% in study children, 29.6% in children with CLDN, and 16.9% in children
      without CLDN (P < 0.01). These prevalences were higher compared with that of a
      group of term siblings (9.3%) (P = 0.05). CONCLUSIONS--These findings suggest
      that CLDN in preterm children is not related to a genetic or familial
      predisposition towards asthma, COPD, or allergy.

PMID- 8535871
TI  - Analysis of fetal and neonatal urine using proton nuclear magnetic resonance
      spectroscopy.
AB  - AIM: To use high field proton nuclear magnetic resonance spectroscopy (1H NMR) to
      characterise the low molecular weight metabolite composition of neonatal and
      fetal urine in relation to gestational age and perinatal outcome. METHODS: The
      first urine passed by two neonatal groups, six full term and five preterm infants
      with normal renal function, was analysed by 1H NMR and compared with fetal urine
      from 14 cases with obstructive uropathy. RESULTS: The mean ratios of taurine, myo
      inositol, and trimethylamine-N-oxide (TMAO) to creatinine were 4.3, 10.1, and
      14.1 times higher, respectively, in the preterm group when compared with those of
      the full term group. Fetal obstructive uropathy was characterised by glycosuria,
      amino and organic aciduria, regardless of gestational age (13-30 weeks).
      CONCLUSIONS: Samples of the first urine passed--that is, urine produced in fetal
      life--by normal preterm infants are useful controls for cases of obstructive
      uropathy detected in the third trimester. 1H NMR will become a clinically useful
      tool for monitoring renal development and abnormalities in utero.

PMID- 8535872
TI  - Catch up growth and pancreatic function in growth retarded neonates.
AB  - To test the hypothesis that relative pancreatic dysfunction is a determinant of
      catch up growth in small for gestational age (SGA) babies, 47 such babies (median
      gestation 38 weeks; range 27-41) and 41 appropriate for gestational age (AGA)
      babies matched for sex, race, and gestational age were recruited. Anthropometry
      was performed within 48 hours of birth and at 6 months. Faecal chymotrypsin
      activities were measured at 0-2 days, 14 days, 6 weeks and 6 months. At 6 months
      30 SGA infants and 25 AGA infants were remeasured. In each group, median stool
      chymotrypsin activities doubled between 0-2 days and 6 months (9.0-25.5 IU/g SGA
      group; 11.6-25.3 IU/g AGA group). SGA babies had significantly lower chymotrypsin
      activities at 14 days (10.9 U/g) than AGA babies (15.5 U/g). In the SGA group
      faecal chymotrypsin activities at 0-2 days were strongly correlated with both
      catch up weight and with catch up length when corrected for the effects of
      birthweight. These data show that impaired pancreatic exocrine function at birth
      is associated with severe intrauterine malnutrition and with impaired catch up
      growth during the first 6 months of life.

PMID- 8535873
TI  - Haemodialysis and ultrafiltration in babies weighing under 1000 g.
AB  - Until now it has not be feasible to haemodialyse babies with renal failure who
      weigh less than 1000 g. Three babies weighing 630, 808, and 1140 g are described.
      They had multiorgan failure and could not be peritoneally dialysed. They were
      treated with veno-venous ultrafiltration and haemodialysis using a manual syringe
      driven technique that required only simple equipment. This method is highly
      labour intensive, but can provide control of fluid volume and plasma biochemistry
      in these very sick infants. Their prognosis, however, is determined by the
      underlying cause of their renal failure, and remains poor.

PMID- 8535874
TI  - Use of specific immunoradiometric assay to determine preterm neonatal insulin
      glucose relations.
AB  - Highly specific immunoradiometric assays were used to measure plasma
      concentrations of insulin, proinsulin, and 32-33 split proinsulin in neonates (n
      = 16). Neonatal plasma insulin concentrations were high relative to blood glucose
      concentrations and compared with adult insulin-glucose relations. Concentrations
      of proinsulin and 32-33 split proinsulin together accounted for 34-70% of the
      total concentration of insulin and pro-peptides. This study confirms the need to
      use a specific assay and neonatal reference data in the diagnosis of neonatal
      hyperinsulinism, and shows that neonatal pancreatic beta cell function may differ
      from that of older subjects.

PMID- 8535875
TI  - Comparison of two reflectance photometers in the assessment of neonatal
      hypoglycaemia.
AB  - To assess the accuracy and reliability of reflectance photometers in estimating
      blood glucose concentrations, two were assessed: the Ames Glucometer 3 (Bayer
      Diagnostics) with Glucofilm Test strips; and the Reflolux S (Boehringer Mannheim)
      with BM Test Glycemia 20-800 strips. These were compared with laboratory blood
      glucose estimations in 100 assays (50 comparisons for each machine, measuring the
      difference (d) between the glucose reading and the mean of the reflectance
      photometer and the laboratory value). The Ames Glucometer 3 (mean d = + 0.7
      mmol/l, (SD 1.1) mmol/l) was less accurate than the Boehringer Reflolux S (mean d
      = 0.2 mmol/l, (SD (0.7) mmol/l). The range of error of both machines is wide
      (Ames 2 SD range + 2.9 mmol/l to -1.5 mmol/l true readings; Boehringer + 1.8
      mmol/l to -1.2 mmol/l of true readings). Because of this, any reflectance
      photometer readings that are even slightly low should be checked with laboratory
      estimations. The clinical value of such machines is limited in infants with low
      blood glucose concentrations.

PMID- 8535876
TI  - Acute effects of two different doses of magnesium sulphate in infants with birth
      asphyxia.
AB  - The effects of two different doses of magnesium sulphate (MgSO4) were evaluated
      in a group of 15 full term infants with Apgar scores of < 6 at 10 minutes,
      studied within 12 hours of delivery. Seven infants received 400 mg/kg MgSO4 and
      eight received 250 mg/kg. After the larger dose, mean arterial pressure (MAP)
      fell by a mean of 6 mm Hg (13%) at one hour but was not significantly reduced
      thereafter. Respiratory depression lasted three to six hours. EEG readings and
      heart rate were not significantly different. Mean serum Mg2+ increased from 0.79
      to 3.6 mmol/l at one hour. After 250 mg/kg MgSO4, MAP, EEG, tone and heart rate
      were unchanged. One infant developed transient respiratory depression. Mean serum
      Mg2+ rose from 0.71 to 2.42 mmol/l at one hour. MgSO4 (400 mg/kg) has an
      unacceptable risk of hypotension; 250 mg/kg MgSO4 was not associated with
      hypotension although respiratory depression can occur.

PMID- 8535877
TI  - Liver transplantation for neonatal haemochromatosis.
AB  - Two cases of neonatal haemochromatosis, a rare and often fatal metabolic
      disorder, presenting with acute liver failure, are reported. Both presented in
      the first week of life with hypoglycaemia, jaundice, and coagulopathy, with rapid
      deterioration of liver function. Both received a transplantation using reduced
      liver grafts. One child was well 18 months later. Few survivors have been
      reported and despite the difficult perioperative management, liver
      transplantation is the best treatment for neonatal haemochromatosis.

PMID- 8535879
TI  - Nellcor Stat Cap differentiates oesophageal from tracheal intubation.
AB  - A trial of the Nellcor Stat Cap, which detects exhaled carbon dioxide, as an aid
      to determining whether endotracheal tubes are placed in the oesophagus or the
      trachea, was carried out in the neonatal unit of this hospital. Twenty five
      neonates, with a mean (range) gestational age of 33 (24-42) weeks and a mean
      (range) birthweight of 2.17 (0.54-4.1) kg were studied over two months. These
      babies underwent a total of 58 intubations and 20 suspected self-extubations. The
      Nellcor Stat Cap was easy to use. It confirmed clinical findings on 20/20
      occasions when the endotracheal tube was in the oesophagus and on 57/58 (98%)
      occasions when it was in the trachea. On 14/78 (19%) occasions the machine
      provided helpful additional information in reaching a decision on the adequacy of
      tube placement. Failure to detect rapidly accidental oesophageal intubation or
      unintentional tracheal extubation can result in rapid deterioration of the
      condition of ventilated newborns. The machine is a valuable aid to intubation and
      rapid diagnosis of self-extubation.

PMID- 8535878
TI  - Autologous umbilical cord blood transfusion.
AB  - The purpose of this study was to examine some aspects of umbilical cord blood
      collection for autologous transfusion in premature infants. All 120
      microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as
      30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2)
      concentrations were quantified at one and 10 minutes after clamping of the cord.
      F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear
      association with time of clamping could be drawn. This means that cord blood
      thrombosis is not activated for at least 10 minutes following clamping of the
      cord. As far as is known, the first newborn infant to benefit from this method of
      transfusion is reported here. The premature infant received two portions of
      autologous blood (on days 5 and 7). No untoward effects were noted. Blood,
      collected from the umbilical cord, is a safe source for autotransfusion, provided
      that bacteriological testing has been carried out.

PMID- 8535880
TI  - Managing acute renal failure in very low birthweight infants.

PMID- 8535881
TI  - Professor Pierre Budin (1846-1907) of Paris, and modern perinatal care.

PMID- 8535882
TI  - Pitfalls of meta-analysis.

PMID- 8535883
TI  - Neonatal meningitis with human parvovirus B19 infection.

PMID- 8535884
TI  - Acute blood pressure response to surfactant administration.

PMID- 8535885
TI  - Outcome of triplet pregnancies.

PMID- 8535886
TI  - Dr Grantly Dick-Read.

PMID- 8535887
TI  - The shoulder--a structure of subtlety.

PMID- 8535888
TI  - Anatomy-specific repair techniques for posterior shoulder instability.
AB  - Forty-one patients with a clinical presentation of posterior shoulder instability
      were treated with one of four surgical techniques designed to correct the
      capsuloligamentous disorder responsible for the instability. The patterns of
      capsuloligamentous disease are identified. The four surgical techniques are
      described and their indications are discussed. At follow-up (mean, 10 months),
      the results were assessed with the Neer-Foster Rating Scale. In 39 of the 41
      patients (95%) outcome was satisfactory.

PMID- 8535889
TI  - Combined arthroscopic management of impingement syndrome and acromioclavicular
      joint arthritis.
AB  - Impingement syndrome and osteoarthritis of the acromioclavicular joint often
      coexist. Failure to address acromioclavicular joint disease can be a common cause
      of failure in the surgical treatment of impingement syndrome. Arthroscopic
      treatment of each of these disorders independently yields more favorable results
      than open procedures. In a patient with both disorders, combined arthroscopic
      subacromial decompression and resection of the distal end of the clavicle can be
      accomplished in one procedure. We evaluated the results of combined arthroscopic
      subacromial decompression and distal clavicle resection in 18 patients who were
      available for a minimum of 2 years' follow-up (average 32 months). Evaluations
      both before and after surgery were done using the UCLA Shoulder Rating Scale.
      Results were good or excellent in 89% of the patients and poor in 11%. The
      average UCLA pain score improved postoperatively for 16 of the 18 patients, while
      the scores for function, strength, and flexion improved for all patients.

PMID- 8535890
TI  - Glenohumeral instability.
AB  - Glenohumeral instability can be defined as pain associated with loss of shoulder
      function due to excessive translation of the humeral head on the glenoid fossa.
      It can be classified according to many factors, such as direction, degree,
      mechanism, and frequency. A thorough understanding of the anatomy and
      biomechanics of the shoulder joint as they relate to instability is helpful in
      understanding the pathophysiology of this condition. All components of the
      instability must be correctly diagnosed so that appropriate treatment can be
      selected. Clinical examination is most important in making the correct diagnosis,
      but plain radiographs, arthrography, computed tomography, magnetic resonance
      imaging, examination under anesthesia, and arthroscopy can be helpful in
      difficult and challenging cases. Conservative treatment with a rehabilitation
      program can be successful in a large percentage of cases and should be the
      initial approach for most patients. Operative treatment is based on the direction
      and type of instability and is recommended only after an adequate trial of
      conservative therapy has failed to improve recurrent instability.

PMID- 8535891
TI  - Patterns of glenohumeral motion loss in patients with chronic rotator cuff
      tendinopathy and subacromial impingement.
AB  - Passive glenohumeral motion loss can occur in patients with chronic rotator cuff
      tendinopathy and subacromial impingement. It is essential for the clinician when
      evaluating patients with rotator cuff symptoms and subacromial impingement to
      assess for concomitant passive glenohumeral motion loss. If rehabilitative
      strategies do not address the motion loss in the shoulder, it is possible that
      the therapeutic rehabilitative intervention will fail.

PMID- 8535892
TI  - Acromioclavicular joint injuries.
AB  - Acromioclavicular joint injuries, including sprains and dislocations, are common
      shoulder problems treated by orthopaedic surgeons. The classification of
      acromioclavicular joint injuries comprises six grades, according to the degree of
      ligamentous disruption and displacement. Grades I and II are generally treated
      nonoperatively, whereas types IV, V, and VI are treated surgically. Treatment for
      grade III injuries remains controversial. Fractures of the distal aspect of the
      clavicle have been divided into three types. Type I fractures are stable and
      require brief immobilization. Type II fractures are unstable and require surgical
      fixation. Type III fractures often require late surgery for acromioclavicular
      arthritis.

PMID- 8535893
TI  - Superior glenoid lesions: a diagnostic and therapeutic challenge.

PMID- 8535894
TI  - Function after amputation, arthrodesis, or arthroplasty for tumors about the
      shoulder.
AB  - A patient with a malignant tumor of the proximal end of the humerus or glenoid
      may be treated with limb-sparing resection or with amputation. Although the
      oncologic and functional characteristics of shoulder amputations have been
      documented, little has been written comparing reconstructive options following
      limb salvage and amputation about the shoulder. This article reviews oncologic
      and functional outcome of patients who have had a malignant skeletal tumor
      adjacent to the shoulder and who have been treated with amputation or limb
      salvage combined with arthrodesis or an allograft/prosthetic reconstruction.

PMID- 8535895
TI  - The SLAPprehension test.

PMID- 8535897
TI  - 3rd International Shock Congress. Act City Hamamatsu, Japan, October 21-23, 1995.
      Abstracts.

PMID- 8535896
TI  - Myositis ossificans after tetanus: treatment aided by quantitative technetium Tc
      99m pyrophosphate radionuclide imaging.
AB  - Functionally disabling myositis ossificans of the posterior aspect of the elbow
      occurred in a 66-year-old man as a sequela of tetanus. Serial quantitative bone
      scans were done to determine the optimal time for excision, which produced an
      excellent functional result without recurrence at 4 years.

PMID- 8535898
TI  - Management strategies for the care of advanced primary and metastatic breast
      cancer.

PMID- 8535899
TI  - The natural history of locally advanced primary breast carcinoma and metastatic
      disease.
AB  - Breast cancer is considered a chronic disease in most women. This belief is based
      on natural history data that suggest that some patients with untreated, advanced
      disease may survive for up to and beyond 20 years after diagnosis. These data are
      corroborated by studies of treated patients in whom breast cancer recurred up to
      15 to 20 years postmastectomy. Conversely, there are also patients who die
      rapidly after presentation. These divergent observations suggest that there are
      at least two subpopulations of patients with breast cancer-one that co-exists
      with the disease and one that rapidly succumbs to it. This heterogeneous biologic
      behavior is likely related to divergent tumor cell growth rates that have been
      documented as well as to other unidentified factors. These two subsets of
      patients, unfortunately, are quite difficult to distinguish. With the promise of
      the ongoing genetic revolution, the hope is that genes associated with rapidly
      progressing disease states can be identified. It is important to be cognizant of
      the prolonged natural history of this disease whenever we attempt to draw
      conclusions regarding a promising new treatment and we must make every attempt to
      ensure that patients are improving because of, rather than despite, a therapeutic
      intervention. Patients entered into trials examining survival as an endpoint
      should make every attempt to follow patients for 20 to 30 years after treatment.
      These considerations will ensure that patients requiring therapy are treated to
      derive benefit, whereas those who would normally not benefit or fare just as well
      without treatment are not exposed to unnecessary morbidity and mortality.
      Finally, it must be concluded as Bloom et al have stated that "the value of
      treatment of primary breast cancer cannot be measured entirely by survival
      statistics." The quality of a patient's remaining life once the diagnosis of
      breast cancer has been made should be considered. From untreated natural history
      data, we know that patients may suffer a painful death without intervention, and
      we are aware as well that overtreatment may impart untoward symptomatic
      consequences in the final stages of life when quality is of paramount importance
      to both the patient and the family.

PMID- 8535900
TI  - Pathology of advanced primary breast carcinoma.
AB  - For a majority of women with breast carcinoma, the clinical course of the disease
      is determined by tumor size and axillary node metastases. Tumor type and grade
      are also important prognostic factors. Estrogen and progesterone receptor
      statuses are good predictors of the likelihood of response to hormone therapy and
      survival. Patients with high S-phase fraction are at increased risk for early
      relapse. As far as other markers are concerned, sufficient information is not
      available currently to make definitive decisions regarding inclusion of their
      assessment in the routine evaluation of breast carcinomas.

PMID- 8535901
TI  - Prediction of recurrence for advanced breast cancer. Traditional and contemporary
      pathologic and molecular markers.
AB  - Approximately 50% of patient with breast cancer ultimately develop metastases,
      among which only 10% to 15% of patients live 5 years or more. Patients with
      locally advanced (stage III) breast cancer have a 5-year survival rate of
      approximately 20% to 30%. Thus, despite high remission rates obtained with
      current therapies, the poor long-term results associated with the apparent
      plateau of response achievable with systemic therapies emphasize the necessity of
      identifying accurate prognostic factors for this group of patients. This will
      allow an informed discussion with the individual patient. In addition, prognostic
      information could be used to guide the therapy and also to identify those
      subgroups of patients who may benefit with less-aggressive therapies.
      Furthermore, in the context of randomized studies, prognostic factors can be used
      to stratify patients. Prognostic factors have been extensively studied in early
      stage breast cancer. In comparison, only a few studies exist on biologic
      prognostic factors in advanced breast cancer. Based on the limited information
      available, it appears that the biologic factors prognostic for locally advanced
      breast cancer are similar to those reported for early-stage breast cancer.
      Apparently, certain factors have a prognostic value irrespective of the stage of
      the disease at the time of presentation. This would then suggest that certain
      factors maintain their significance as the breast cancer progresses from an
      overtly local to a systemic disease. It is already well recognized that
      histologic grade is a significant prognostic factor for early-stage as well as
      metastatic breast disease. Hormone receptors have been reported to be of
      prognostic value at all stages of disease. Proliferation rate assessed by a
      variety of techniques as well as determination of the Nottingham Primary
      Prognostic Index provides important information about the rate of the growth of
      the tumor. Thymidine labeling index and S-phase fraction also provide information
      in regard to response to chemotherapy. DNA ploidy has been reported to be of
      significance in prediction of response to adjuvant chemotherapy and to a lesser
      extent to hormone therapy. The value of DNA ploidy in relation to survival in
      advanced breast cancer, however, remains controversial. Other prognostic factors
      such as oncogenes, tumor suppressor genes, and growth factors have also shown
      some predictive value in advanced breast cancer. Similar to what has also been
      suggested in early breast cancer, much research still needs to be done to clarify
      the role of currently available prognostic factors and to identify new, more
      powerful discriminants.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8535902
TI  - Comorbidity risk parameters associated with advanced breast cancer and systemic
      disease. Management of nonbreast disease.
AB  - The comorbidity risks associated with advanced breast cancer and systemic disease
      have been outlined under three broad categories: the local or regional
      consequences of advanced local breast cancer and its management, systemic
      sequelae of adjuvant chemotherapy and radiotherapy, and systemic sequelae of
      metastatic breast disease. Awareness of the potential risks, early detection, and
      active intervention may diminish the adverse consequences of comorbidities in
      breast cancer and improve the patient's quality of life.

PMID- 8535903
TI  - Breast conservation following induction chemotherapy for locally advanced
      carcinoma of the breast (stages IIB and III). A surgical perspective.
AB  - We have now employed induction chemotherapy in almost 200 women with locally
      advanced breast carcinoma. Significant tumor regression has been noted in a
      majority of patients, 85%, permitting definitive local treatment with greater
      success than heretofore expected. Breast conservation has been offered to a
      larger proportion of these women as we have gained experience with this
      technique, with outcome equivalent to that of mastectomy in these highly selected
      patients. Our previously dismal outlook for patients with advanced local disease
      has been replaced by a more optimistic attitude. Our achievements with this
      initial group of patients and currently with stage II patients as well is most
      encouraging. Breast conservation has been offered to a larger proportion of these
      women, with outcome equivalent to mastectomy. We hope that our limited but
      encouraging experience with these patients will stimulate other investigators to
      embark upon similar studies of induction chemotherapy for women with stages II
      and III, and even earlier, breast cancer.

PMID- 8535904
TI  - Surgical and medical management of local-regional treatment failures in advanced
      primary breast cancer.
AB  - The strength in the management of locally advanced breast cancer lies in the team
      approach to multimodality care. The oncologist must be a careful listener and
      incorporate the patient's perspective of her goals before arriving at a final
      decision about a treatment plan for either the initial presentation of the
      disease or its locoregional relapse. Treatment strategies based on the genetic or
      biologic features of breast cancer arising within the individual patient are
      currently being investigated.

PMID- 8535905
TI  - Contemporary adjuvant treatment of breast cancer.
AB  - Adjuvant therapy with either chemotherapy or hormonal therapy offers
      statistically significant benefits for most subsets of women with breast cancer
      that in many cases outweigh the risks of treatment, but the potential benefit
      will vary from patient to patient and by modality of therapy. The absolute
      reduction in risk is proportional to the overall risk of relapse or death, so
      greater absolute benefit can be anticipated for those with a greater risk.
      Consensus recommendations provide a reasonable outline for initiating the
      discussion of adjuvant therapy, but treatment considerations must be
      individualized to take into account the patient's personal willingness to accept
      these weighed estimates of objective probabilities of benefit, toxicity, and
      risk. Many questions remain and will be answered only through the clinical trials
      process. Every patient with breast cancer should be given the opportunity to
      consider participation in a clinical trial when appropriate for both the sake of
      medical knowledge and the benefit of future patients.

PMID- 8535906
TI  - Combined modality approach for high-risk breast cancer. The Milan Cancer
      Institute experience.
AB  - After 20 years of successive clinical trials, the results achieved at the Milan
      Cancer Institute have helped to establish the effectiveness of adjuvant
      combination chemotherapy in high-risk women with resectable breast cancer. The
      most significant findings can be summarized as follows: (1) the clinical benefit
      in terms of relapse-free and total survival can be prolonged up to 20 years from
      surgery; (2) the use of anthracyclines (doxorubicin) can contribute to improved
      treatment outcome; (3) dose intensity and dose size are the leading prognostic
      variables; and (4) adjuvant treatments are not associated with important
      iatrogenic morbidity. New modalities that could profoundly change current
      treatment strategies will involve high-dose sequential chemotherapy and primary
      chemotherapy. In fact, the use of rhG-CSF-elicited hematopoietic progenitors will
      grant a substantial reduction in granulocytopenia and related toxicities; this,
      in turn, will permit the administration of regimens based on high dose size and
      dose intensity. As far as primary chemotherapy is concerned, the shift from
      mutilating to breast-conserving operations has led to important advantages in a
      society concerned for body integrity. In the few studies with sufficient follow
      up, objective tumor response to primary chemotherapy has been translated into
      superior relapse-free survival compared with that of nonresponders. In
      particular, from the first Milan study the knowledge is clearly emerging that the
      response rate is inversely related to the initial tumor volume and that the
      degree of tumor regression (complete pathologic remission versus moderate versus
      minimal response) appears to represent a marker of outcome. Should this crucial
      observation be confirmed in other ongoing trials, then the amount of tumor
      shrinkage could rank among the most important prognostic variables because it is
      reproducible and inexpensive. As a consequence, the achievement of complete (or
      near complete) pathologic remission will become the major goal of properly
      intensified drug regimens to ensure a durable relapse-free survival rate. To make
      legitimate the wide adoption of the strategy involving primary chemotherapy, most
      breast cancer specialists correctly advocate that the initial promising results
      be validated through classic randomized trials. The question to answer appears
      simple: Will preoperative chemotherapy be superior to postoperative chemotherapy
      in terms of relapse-free and total survival? In our opinion, the simple attempt
      to shift from postoperative (adjuvant) to preoperative (primary) chemotherapy may
      not be enough, although formally correct, to maximize treatment outcome, and thus
      become the new strategy of choice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535907
TI  - Combined modality treatment of stage III and inflammatory breast cancer. M.D.
      Anderson Cancer Center experience.
AB  - Seven hundred fifty-two patients with stage III disease (of those, 178 patients
      with inflammatory carcinoma) were treated with a combined modality approach at
      our institute in seven prospective studies. After three to four cycles of
      chemotherapy, each patient was treated with local therapy. An estimated 54% of
      patients with stage IIIA disease and 24% of patients with stage IIIB disease were
      free of disease. An estimated 30% of patients with inflammatory carcinoma of
      breast were free of disease beyond 10 years with this approach.

PMID- 8535908
TI  - The role of bone marrow transplantation in the management of advanced local
      disease.
AB  - The applications of bone marrow transplantation for the management of advanced
      local disease are examined. This review for stage III and inflammatory carcinoma
      suggests enhanced effectiveness and a progressive decrease in costs for bone
      marrow transplantation.

PMID- 8535909
TI  - Hormonal treatment of advanced breast cancer.
AB  - Endocrine therapy for breast cancer has been used for almost a century, but
      because of the enormous success of tamoxifen there has been a resurgence of
      interest by the pharmaceutical industry to develop new and innovative endocrine
      therapies. Overall, the strategy is quite simple. Estrogen stimulates growth;
      therefore, the goal is to deny the breast tumor estrogens. Tamoxifen accomplishes
      this by blocking the estrogen receptor. The new antiestrogens, toremifene and
      droloxifene, however, appear to have no greater activity than tamoxifen in the
      treatment of advanced disease and therefore may ultimately offer no advantages
      over current therapy. In contrast, the pure antiestrogens hold additional promise
      as they may produce a more profound inhibitory effect on the tumor, and the
      response may be maintained longer. An orally active, pure antiestrogen, however,
      would be an important advance. The strategy of using GnRH agonists for
      premenopausal patients clearly has merit to produce a chemical oophorectomy. The
      strategy could be integrated into the general treatment plan for the young
      premenopausal patient taking tamoxifen who may not have had her menstrual cycles
      stopped by combination chemotherapy. The GnRH agonists would block the reflex
      rise in estradiol caused by tamoxifen therapy and ultimately produce a more
      efficient antihormonal therapy. Indeed, the different specific aromatase
      inhibitors can also be integrated into the treatment plan to produce a complete
      estrogen blockade. Whether the use will be found to be superior to pure
      antiestrogens, however, must await the completion of comparative clinical
      studies. If all the results of endocrine therapy are therapeutically similar, the
      final strategy may depend on the acceptability by the patient of an individual
      delivery method for each pharmaceutical approach.

PMID- 8535910
TI  - Endocrine and cytotoxic therapies for the management of advanced local breast
      cancer. Current clinical investigation.
AB  - There is a need for more clinical investigation in advanced local breast cancer.
      Both chemotherapy and endocrine therapy improve disease-free and overall survival
      and are now a routine part of standard patient care. Dose-intensive chemotherapy
      should be reserved for younger patients in large, controlled clinical trials. For
      operable patients, adequate surgical therapy of the breast and axilla remains a
      standard of care and provides the most important piece of prognostic information
      (i.e., the number of involved axillary lymph nodes). Tamoxifen treatment of the
      estrogen receptor-positive postmenopausal patient remains the standard, although
      chemotherapy may add a further increment to disease-free survival.

PMID- 8535911
TI  - Prognostic value of transvaginal sonography in asymptomatic endometrial cancers.
AB  - In the period between 1985 and 1991, 83 postmenopausal women with endometrial
      cancer were examined by transvaginal sonography. None of them were on hormone
      replacement therapy and all had amenorrhea of more than 2 years. Twenty-two were
      asymptomatic and had an endometrial cancer detected by transvaginal sonography
      and 61 showed atypical bleeding as their only clinical symptom. Women with
      asymptomatic endometrial cancers detected by transvaginal sonography exhibited
      significantly less mean myometrial tumor infiltration and more well
      differentiated tumors than those with atypical bleeding (4 mm and 45% compared
      with 10 mm and 18%, respectively). In 75% of the cases the estimation by
      transvaginal sonography of tumor stage completely agreed with the histological
      staging. These preliminary data show that asymptomatic endometrial cancers
      screened by transvaginal sonography are likely to have a better prognosis than
      symptomatic cancers. Furthermore, transvaginal sonography can be used as a
      reliable tool for tumor staging prior to surgery or radiotherapy.

PMID- 8535912
TI  - Endometrial assessment by transvaginal sonography and histological findings after
      D & C in women with postmenopausal bleeding.
AB  - A total of 149 women with postmenopausal bleeding underwent transvaginal
      sonography, hysteroscopy and dilatation and curettage in order to study the
      diagnostic accuracy of several ultrasound parameters in assessing endometrial
      pathology and to determine the most sensitive cut-off value of endometrial
      thickness for the exclusion of endometrial lesions. In distinguishing
      pathological from normal endometrium, transvaginal sonography showed a
      sensitivity of 69.3%, specificity of 82.7%, positive predictive value of 74.1%
      and negative predictive value of 72.1%. In detecting premalignant and malignant
      endometrial pathology, transvaginal sonography showed a sensitivity, specificity,
      positive predictive value and negative predictive value of 55%, 96.1%, 68.7% and
      93.2%, respectively. Considering endometrial thickness as a single parameter, the
      most sensitive cut-off for defining normality was 4 mm; nevertheless, in the
      group of patients that had an endometrial thickness less than 4 mm, there was one
      case of malignancy (sensitivity, 95.2%; specificity, 49.4%; positive predictive
      value, 57.3%; and negative predictive value, 93.5%). Transvaginal sonography
      combined evaluation (morphology, thickness and color Doppler) showed a poor
      diagnostic accuracy in detecting endometrial pathology and in differentiating
      between endometrial benign lesions, endometrial polyps and adenocarcinoma in
      women with postmenopausal bleeding. Endometrial thickness evaluated with
      transvaginal sonography was preferable but not sensitive enough to exclude
      endometrial pathology.

PMID- 8535913
TI  - Changes mimicking endometrial neoplasia in postmenopausal, tamoxifen-treated
      women with breast cancer: a transvaginal Doppler study.
AB  - In menopausal patients with breast cancer who receive tamoxifen therapy,
      transvaginal sonography may show an abnormal endometrium. Our objective was to
      evaluate the effects of prolonged tamoxifen therapy on endometrial blood flow in
      postmenopausal patients with breast cancer, and to correlate blood flow
      characteristics with the sonographic appearance of the endometrium and its
      pathology. Transvaginal color Doppler ultrasound examinations were performed on
      45 postmenopausal women (age range 54-70 years) with breast cancer, who had been
      treated with tamoxifen for 1-3 years. Twenty women (Group 1) had a thick,
      irregular, cystic endometrium of > or = 5 mm, and 25 (Group 2) showed a thin
      endometrium of < 5 mm. The blood flow response was assessed by visualization of
      arterial waveforms in the endometrial and subendometrial regions with a
      transvaginal color flow imaging system. Resistance indexes (RI) were calculated
      for analysis and correlated with endometrial appearance and histology. The mean
      RI in Group 1 was 0.39 +/- 0.10 (range 0.32-0.54), while the mean RI in Group 2
      was 0.79 +/- 0.10 (range 0.54-0.90; p < 0.001). On histology, 12 patients in
      Group 1 showed atrophic endometria confirmed by hysteroscopy, while in the
      remaining eight, endometrial polyps were found. In Group 2, all patients had
      scanty, atrophic endometria. Six of the eight patients with endometrial polyps
      had an RI of < 0.4 and none had malignant changes. These data suggest that
      tamoxifen therapy in women with postmenopausal breast cancer induces endometrial,
      morphological and blood flow changes, mimicking endometrial neoplasia.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8535914
TI  - Sonographic features of tuberculous peritonitis with female genital tract
      tuberculosis.
AB  - Our aim was to illustrate the sonographic features of tuberculous peritonitis
      with female genital tract tuberculosis in an attempt to facilitate the
      recognition of the disorder preoperatively. Transabdominal and transvaginal
      sonographic features and the findings from laparotomy/laparoscopy, endometrial
      biopsy and microbiology were reviewed and compared in 15 patients with
      tuberculous peritonitis with female genital tract tuberculosis. Of the 15
      patients, 12 had wet tuberculosis and three had dry (adhesive) tuberculosis.
      Sonographic features of wet tuberculosis were categorized as follows: septated
      ascites (ten patients), particulate ascites (two patients), loculated fluid (two
      patients), thickened peritoneum (eight patients), thickened omentum (eight
      patients), adnexal mass (11 patients), adhesions (seven patients) and endometrial
      involvement (five patients). Adnexal masses, adhesions and loculated fluid were
      found to be present in the dry type. When sonographic findings were compared with
      those of laparotomy and/or laparoscopy and/or endometrial biopsy, ultrasound was
      able to identify aspects of tuberculosis infection as follows: ascites/loculated
      fluid, 13/13 (100%); adnexal mass, 12/13 (93%); peritoneal thickening, 9/13
      (69%); omental thickening, 8/13 (61%); and endometrial involvement, 5/6 (83%). We
      conclude that awareness of the sonographic changes associated with tuberculosis
      infection may improve diagnostic accuracy, and avoid clinical mismanagement and
      surgical explorations in the wet type of tuberculosis.

PMID- 8535915
TI  - The reliability of transvaginal ultrasonography to detect retained tissue after
      spontaneous first-trimester abortion, clinically thought to be complete.
AB  - In order to assess the reliability of transvaginal ultrasonography for the
      detection of trophoblastic tissue retained after spontaneous first-trimester
      abortion and clinically thought to be complete, the clinical, sonographic and
      pathological data of 33 women were retrospectively analyzed. The patients' mean
      age was 34 years (range 24-48). The mean gestational age at presentation of
      symptoms was 8 weeks (range 5.1-11.1). Transvaginal sonography showed that in 18
      cases retained tissue was absent, and that in 15 patients, retained trophoblastic
      tissue was suspected. Pathological reports (following dilatation and curettage)
      confirmed the absence of retained tissue in 17 cases and demonstrated its
      presence in 16 patients (13 in whom retained tissue was suspected by sonography
      and three in whom retained tissue was not suspected). Sensitivity, specificity,
      positive predictive value and negative predictive value in our series were 81%,
      94%, 93% and 83%, respectively for the detection of retained trophoblastic
      tissue. We conclude that transvaginal ultrasonography is a reliable method to
      detect the presence of retained trophoblastic tissue following spontaneous first
      trimester abortion, clinically thought to be complete.

PMID- 8535916
TI  - Postpartum surveillance of urinary retention by ultrasonography: the effect of
      epidural analgesia.
AB  - Our objective was to investigate by ultrasonography whether the risk for
      postpartum urinary retention is increased following administration of epidural
      analgesia during labor and delivery. In a prospective study, 106 healthy women
      who had undergone vaginal delivery were evaluated. Sixty-eight of the women had
      received epidural analgesia during labor and delivery. All subjects had an
      ultrasound examination at a mean of 42 h after delivery, and residual urine
      volume was estimated immediately after voiding. Correlations among obstetric
      parameters, epidural analgesia and residual urine volumes were evaluated. The
      mean accuracy rate of ultrasonography for estimation of bladder volumes was +/-
      10.2%. No cases of clinically evident urinary retention were diagnosed in the
      total puerperal population. There were no significant differences between the
      groups in the average amounts of residual urine as measured by ultrasonography.
      With modern obstetric practice, epidural analgesia for labor is not associated
      with an increased risk for postpartum urinary retention. The non-invasive nature
      of ultrasound renders it especially attractive and useful for measuring residual
      urine volume in postpartum patients. The safety, simplicity and relative comfort
      of this method over-ride the slightly imperfect calculations that it currently
      yields, and makes it preferable to catheterization or cystometry for evaluation
      of residual urine volume.

PMID- 8535917
TI  - The effect of feedback on anxiety levels during ultrasound scanning for ovarian
      cancer.
AB  - Women undergoing ultrasound scanning for the detection of ovarian cancer benefit
      psychologically from the examination, which has been shown to reduce levels of
      anxiety, depression, hostility and complaints about somatic symptoms. However, it
      is not completely clear what aspects of the ultrasound examination are
      responsible for these effects, and how these beneficial psychological effects
      vary under different circumstances. This study examined, in particular, the
      effect of various levels of feedback on patients' anxiety levels before and after
      ultrasound examination. Two hundred and seven women were randomly assigned to two
      different experimental conditions: high feedback and low feedback. The subjects'
      levels of anxiety (both trait and state anxiety) were measured immediately before
      and after the ultrasound examination. The women's individual risk factors for
      ovarian cancer were also recorded. This study showed a significant decrease in
      the level of trait anxiety following ultrasound scanning. The decrease in anxiety
      did not relate to the level of feedback provided to the patients, nor to the
      woman's degree of risk for ovarian cancer. The results are discussed in terms of
      possible implications for clinical care and the allocation of resources in the
      medical system.

PMID- 8535918
TI  - Prospective study on fetal weight estimation using limb circumferences obtained
      by three-dimensional ultrasound.
AB  - The aim of this prospective study was to evaluate the usefulness of fetal weight
      estimation in a prospective study, based on formulae derived from a previous
      retrospective study, using forward stepwise multiple regression analysis. Three
      dimensional ultrasound was used to make reproducible measurement of limb
      circumferences, which formed the basis of our models. A total of 213 women with
      singleton pregnancies were scanned in the week prior to delivery and the
      following variables were measured: biparietal diameter, head circumference,
      transverse abdominal diameter, abdominal circumference, femur length, thigh
      circumference and arm circumference. The whole population was divided into three
      subgroups according to the abdominal circumference (< 10th centile, 10-90th
      centile, and > 90th centile). We demonstrated the need for only two models for
      accurate fetal weight estimation, one for the small-for-dates fetuses and a
      second for the others. The most accurate results were obtained for the macrosomic
      fetuses with a standard deviation of 8.8%. Our data confirm the usefulness of
      measurement of fetal thigh circumference for the the small-for-dates-fetuses and
      arm circumference for the other groups. We concluded that the use of three
      dimensional ultrasound could facilitate the accurate prediction of fetal weight.

PMID- 8535919
TI  - Transvaginal color Doppler and pelvic tumor vascularity: lessons learned and
      future challenges.

PMID- 8535920
TI  - Ethnic differences in fetal growth.

PMID- 8535921
TI  - Evaluating the endometrium of postmenopausal women with transvaginal
      ultrasonography.

PMID- 8535922
TI  - Transvaginal gray-scale and Doppler ultrasound examinations of the uterus and
      ovaries in healthy postmenopausal women.
AB  - The aim of this study was to elicit reference data representative of normal
      findings at transvaginal gray-scale and Doppler ultrasound examination of the
      uterus and ovaries in postmenopausal women. A total of 144 asymptomatic
      postmenopausal women with normal findings at clinical gynecological examination
      were included in the study. They underwent transvaginal sonography including
      Doppler measurements of blood flow velocity in the uterine and ovarian arteries.
      Ninety-eight (68%) women had a normal uterus and normal or non-visible ovaries at
      ultrasound examination, 23 (16%) had small uterine myomas but normal or non
      visible adnexa, 19 (13%) had small adnexal cysts but a normal uterus, and four
      (3%) had both small myomas and small adnexal cysts. The median time-averaged
      maximum velocity (TAMXV) and pulsatility index (PI) values for the right and left
      uterine artery of normal uteri (n = 117) were 10.4 cm/s (range 2.2-43.0) and 10.6
      cm/s (2.9-30.8), and 2.33 (0.97-5.13) and 2.35 (0.98-4.58), respectively. Median
      volumes of the normal right (n = 93) and left ovaries (n = 90) were 1.3 cm3 (0.4
      3.7) and 1.2 cm3 (0.4-3.0), respectively, and median TAMXV and PI values for the
      stromal arteries in the normal right (n = 53) and left ovaries (n = 54) were 2.1
      cm/s (1.3-4.6) and 2.3 cm/s (1.1-7.3), and 1.31 (0.65-2.61) and 1.26 (0.63-1.85),
      respectively. Our results provide a basis for gray-scale and Doppler ultrasound
      studies of pathological conditions in the female pelvis after the menopause.

PMID- 8535923
TI  - Interobserver agreement in the results of Doppler examinations of extrauterine
      pelvic tumors.
AB  - The aim of this study was to evaluate interobserver agreement in the results of
      Doppler measurements of peak systolic velocity (PSV), time-averaged maximum
      velocity (TAMXV) and the color content of tumor scans in extrauterine pelvic
      tumors. The results of transvaginal color and spectral Doppler examinations of 66
      extrauterine pelvic masses obtained by two observers experienced in
      ultrasonography were compared. Each observer aimed to obtain the highest possible
      Doppler shift from arteries in the wall, septa and solid parts of each tumor.
      Tumor vascularization was assessed in terms of the 'tumor color score', i.e. the
      color content of the Doppler scan as rated for the tumor as a whole by each
      observer on a visual analog scale. The tumors were classified according to
      arbitrarily chosen cut-off limits for the tumor color score, the highest tumor
      TAMXV and the highest tumor PSV. Inter-class correlation coefficient values for
      TAMXV and PSV were < or = 0.75, whereas that for tumor color score was 0.89.
      Interobserver agreement was complete for the detection of color in tumors (Kappa
      value 1.0), excellent for the recording of arterial Doppler shift spectra from
      tumors (Kappa value 0.82), and moderate or good for classifying tumors based on
      cut-off limits for TAMXV, PSV (Kappa values ranging from 0.44 to 0.67) and tumor
      color score (Kappa values ranging from 0.59 to 0.66).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8535924
TI  - Measuring the thickness--is that all we have to do for sonographic assessment of
      endometrium in postmenopausal women?
AB  - For sonographic assessment of the endometrium in postmenopausal women,
      measurement of the maximum thickness is used in many cases as the sole criterion.
      The cut-off values stated in the literature, however, vary considerably. This
      prospective study examined 200 female patients in order to ascertain the value of
      echomorphology in addition to endometrial biometry. Up to an overall endometrial
      thickness of 3 mm, we observed only histologies without any pathological
      findings, whereas from an endometrial thickness of 10 mm upwards, only polyps,
      hyperplasias and carcinomas were found. In more than a third of our patients, the
      endometrial thickness was between 3 and 10 mm where the structure of the
      endometrium could reflect the possible histological finding: homogeneity, low
      echo and a sonographically depictable central echo between symmetrical
      endometrial leaves were an indication for absence of pathological findings,
      whereas heterogeneity and high echogenicity were pointers for pathological
      changes. In contrast to the sole measurement of endometrial thickness in the
      postmenopause, the combined metric and morphological parameters improve not only
      the predictability of pathological findings but, above all, the selectivity of
      the vaginosonographic assessment of the endometrium in postmenopausal women.

PMID- 8535925
TI  - Immune response of the skin.

PMID- 8535927
TI  - Cytochromes P450 and drug toxicity. Immunological consequences.

PMID- 8535926
TI  - Predictive molecular and genetic toxicology. Application to the detection of
      sensitizing potential of xenobiotics.

PMID- 8535928
TI  - Molecular genetics of cytochrome P450 IID. Anomalies of drug metabolism.

PMID- 8535930
TI  - Allergy and intolerance to nonsteroidal anti-inflammatory agents.

PMID- 8535931
TI  - Place of excipients in drug-related allergy.

PMID- 8535929
TI  - Drug-induced "allergic hepatitis".

PMID- 8535933
TI  - The management of adverse drug reactions.

PMID- 8535932
TI  - Diagnosis of drug allergic reactions.

PMID- 8535934
TI  - Infections linked to lax handling of propofol.

PMID- 8535935
TI  - Contradictory hormone studies renew debate over breast cancer link.

PMID- 8535936
TI  - New drug counters doxorubicin cardiotoxicity; not for use at start of
      chemotherapy.

PMID- 8535937
TI  - Mycophenolate approval provides new option for organ-rejection prevention.

PMID- 8535938
TI  - Treatment for impotence gains FDA approval.

PMID- 8535939
TI  - Closing poison control centers is fiscally foolish.

PMID- 8535940
TI  - Changes in U.S. patent law for pharmaceuticals.

PMID- 8535941
TI  - Handling the first dose of a questionable order.

PMID- 8535942
TI  - Pharmacy and the Internet.

PMID- 8535943
TI  - The Code of Ethics for pharmacists.

PMID- 8535944
TI  - The ethics of leadership in pharmacy.
AB  - The pharmacy profession's responsibility to provide ethical leadership to its
      members is explained, and areas where pharmacy should take a leadership role are
      described. Changes taking place in health care offer many opportunities for
      pharmacy in its transformation into a fully clinical discipline. The profession
      needs to address the ethical issues that will affect it as part of this
      revolution. The role pharmacy is taking to eliminate medication misadventuring
      will be a test case for the profession's ability to exert the leadership it must,
      as part of its new definition of itself. Pharmacy needs to define the structure,
      process, and outcomes necessary to improve its own practice to avoid drug
      misadventuring, with a clear set of practice and ethical standards, and engage
      medicine and nursing to adopt similar standards. Pharmacy should also take a
      leadership role in health care reform, working with other clinicians to ensure
      that the changes provide better outcomes for patients. Health care professionals
      are bound together by a common moral purpose: to act in the patient's best
      interest. Thus, each health profession is a moral community, which must determine
      and promote ethical behavior among its members. Pharmacy must practice ethical
      leadership: it must define and prove its contribution to patient outcomes,
      further develop legal and ethical standards, and examine its responsibilities for
      vulnerable patient groups such as children. It must work to overcome the
      traditional dominance of medicine; pharmacy, nursing, and medicine must come
      together in service of the patient and develop a cross-professional conception of
      ethics. Pharmacy also must participate in the broader debate about health care.
      Pharmacy has begun to take a leadership role among the health professions through
      its efforts to eliminate medication misadventuring. Additional leadership
      challenges for the profession are suggested.

PMID- 8535945
TI  - Immunotherapy in multiple sclerosis, Part 2.
AB  - The efficacies of corticosteroids and azathioprine (part 1) and of
      cyclophosphamide, immune globulin, cyclosporine, interferons, copolymer 1, and
      cladribine (part 2) in patients with multiple sclerosis (MS) are reviewed. MS is
      an inflammatory, demyelinating disease of the CNS that commonly affects young
      adults. The involvement of various immune mechanisms in MS suggests a role for
      immunomodulating therapy. The goals of immunotherapy vary with the clinical stage
      of the disease and include (1) improving recovery from exacerbations, (2)
      decreasing the number or severity of relapses, (3) preventing the development of
      chronic progressive disease from a relapsing-remitting course, and (4) decreasing
      further progression in patients with chronic progressive disease. In clinical
      trials, corticotropin and corticosteroids have been found to accelerate recovery
      from exacerbations. Tapering is often effective after high-dose induction
      therapy. Long-term maintenance regimens do not alter disease progression and are
      not recommended. Azathioprine produces modest benefits with respect to relapse
      rates and disease progression after two or more years of treatment; adverse
      effects are mild to moderate. Azathioprine should not be used in patients with
      aggressive disease who may approach severe disability in 6-18 months.
      Cyclophosphamide, because of its modest impact on disease progression and its
      potentially severe adverse effects, including cancer, should be reserved for
      patients with aggressive relapsing-remitting or chronic progressive disease in
      whom other treatments have failed to work; maintenance therapy is necessary after
      induction. Intravenous immune globulin may benefit patients with severe relapses;
      however, its efficacy remains unproven. Cyclosporine also cannot be recommended
      because of its modest efficacy, marked adverse effects, and high cost. Interferon
      beta-1b is a more specific immunotherapy that has been found to decrease the
      number and severity of relapses. This treatment should be considered in patients
      with relapsing-remitting disease who are having two or more exacerbations per
      year. Copolymer 1 and cladribine have shown some promising early results.
      Although various immunotherapeutic drugs can provide relief in patients with MS,
      none is capable of reversing disease progression, and some can cause serious
      adverse effects. Better understanding of the immunologic basis of MS may lead to
      more specific immunotherapies with more lasting benefits.

PMID- 8535946
TI  - Pharmacy involvement in patient-focused care in Florida hospitals.
AB  - Hospital pharmacy directors in Florida were surveyed to determine the effects of
      patient-focused care on pharmacy practice. In a statewide mail survey in 1994,
      directors were asked whether their hospital had implemented patient-focused care
      or was planning to, what factors influenced this, whether and how the pharmacy
      was involved, what changes in structure and services resulted, and how they
      perceived the impact of patient-focused care on the practice of hospital
      pharmacy. They were asked to identify specific programs, interdisciplinary teams,
      and opportunities associated with patient-focused care programs. Usable surveys
      were returned by 148 respondents (48.8% response rate). Fifty-three (35.8%) of
      the respondents had implemented patient-focused care and 50 (34%) were planning
      to ; 82.5% of these respondents (85 of 103) said pharmacists were involved in the
      planning efforts. Respondents said hospital administration was most often
      responsible for initiating patient-focused care, and cost was the top-ranked
      reason. For pharmacy, patient-focused care brought more interdisciplinary
      activities and new services. Florida hospital pharmacy directors thought patient
      focused care would change the practice of pharmacy and that the change would be
      positive.

PMID- 8535947
TI  - Compounding of preservative-free high-concentration morphine sulfate injection.
AB  - The compounding of a preservative-free high-concentration morphine sulfate
      injection from nonsterile morphine sulfate is described. High-concentration (50
      mg/mL) morphine sulfate injection is compounded by dissolving Morphine Sulfate
      Powder, USP, in preservative-free sterile water for injection. The solution is
      pumped through 0.8- and 0.22-micrometer filters into 10-mL sterile vials and
      quarantined until assays for concentration, sterility, and bacterial endotoxins
      have been performed. The solution is placed in active inventory and dispensed to
      nursing units as needed. Total compounding cost per 10-mL vial of morphine
      sulfate injection is about $9. The expiration date is six months from the date of
      compounding. This solution has been administered i.m., s.c., i.v., and epidurally
      to inpatients with advanced cancer and severe pain at an acute care hospital. An
      acute care hospital compounds batches of preservative-free high-concentration
      morphine sulfate injection from nonsterile morphine sulfate.

PMID- 8535948
TI  - Long-term stability of interferon alfa-2b diluted to 2 million units/mL.

PMID- 8535949
TI  - Potential interaction between isoniazid and selective serotonin-reuptake
      inhibitors.

PMID- 8535950
TI  - Diluted effect from diluted mesalamine rectal suspension?

PMID- 8535951
TI  - Tardive dyskinesia revisited.

PMID- 8535952
TI  - Ocular hypotensive effects of L-arginine and its derivatives and their actions on
      ocular blood flow.
AB  - Effects of L-arginine and some related compounds on the intraocular pressure
      recovery (IOPR) and ocular blood flow in rabbits had been studied. It was found
      that L-arginine (RVC-579) and N alpha-benzoyl-L-arginine ethyl ester (RVC-578)
      delayed the IOPR markedly: The IOPR of the contralateral non-treated eye was
      delayed to the same extent as the treated eye. The effects of closely related
      congeners L-(+)-canavanine (RVC-581) and L-homoarginine (RVC-580) on the IOPR
      were qualitatively similar to RVC-579 and RVC-578 but less effective. RVC-578 was
      found to increase the blood flow significantly in ciliary body, retina and
      choroid. On the other hand, NG-nitro-L-arginine, a nitric oxide (NO) synthase
      inhibitor, reduced the blood flow in choroid at 60 and 120 min after drug
      administration and did not increase the blood flow in iris, ciliary body and
      retina. These results indicate that L-arginine and its derivative are capable of
      lowering the IOP possibly through the formation of nitric oxide to relax the
      blood vessel and to reduce the IOP as a result.

PMID- 8535953
TI  - Drug effects on intraocular pressure and vascular flow in the bovine perfused eye
      using radiolabelled microspheres.
AB  - A novel technique is described in which the effect of the beta-adrenoceptor
      antagonists timolol and carteolol, and the vasodilators sodium nitroprusside
      (SNP) and verapamil on intraocular pressure (IOP) and the distribution of ocular
      flow in the bovine arterially perfused eye is investigated using radiolabelled
      microspheres. At maximum IOP-reducing dose timolol was found to significantly
      reduce perfusion in the choroid and, at higher dose, it was found to
      significantly reduce perfusion in the iris. By contrast, a maximal IOP-reducing
      dose of carteolol markedly reduced perfusion in the iris, ciliary body and
      choroid. Vasoconstriction induced by carteolol was not inhibited by the alpha
      antagonist phentolamine. Against a background of vascular tone induced by
      noradrenaline, SNP and verapamil were found to significantly increase perfusion
      in the iris, ciliary body and choroid. The effects of these drugs upon the
      vasculature of the bovine perfused eye are varied and complex and may not bear a
      direct relationship to their ocular hypotensive effect.

PMID- 8535954
TI  - Apraclonidine protection of the blood-aqueous barrier from traumatic break-down.
AB  - This study investigated the effects of apraclonidine hydrochloride 1% eye drops
      on blood-aqueous barrier in 108 pigmented rabbits. The effects of pretreatment
      with dapiprazole and yohimbine, and a comparison with clonidine 0.125% eye drops
      are also reported. The disruption of blood-aqueous barrier was obtained by argon
      laser burning of the iris. The degree of permeability of the barrier was deduced
      by the amount of proteins in aqueous humor 60 min after laser application.
      Intraocular pressure and pupil diameter were also studied. Protein content in
      aqueous humor was 0.72 +/- 0.26 g/l in control rabbits that did not receive any
      treatment; 5.98 +/- 4.23 g/l in rabbits instilled with placebo eye drops and
      treated by laser burning of iris; 0.43 +/- 0.25 g/l in rabbits that received
      apraclonidine eye drops prior to laser burning; 2.19 +/- 1.3 g/l in rabbits that
      received apraclonidine eye drops immediately after laser application; 0.35 +/-
      0.08 g/l in rabbits that received apraclonidine 1% eye drops both before and
      after laser application. Rabbits treated with clonidine 0.125% had a protein
      content in aqueous humor of 5.45 +/- 2.08 g/l after laser application.
      Dapiprazole 0.5% eye drops prior to apraclonidine led to a protein content in
      aqueous humor of 1.93 +/- 2.13 g/l; yohimbine 0.3% eye drops prior to
      apraclonidine led to a protein content of 0.70 +/- 0.40 g/l. Protein content in
      aqueous humor was 0.93 +/- 0.36 g/l, 0.82 +/- 0.899 g/l and 1.68 +/- 1.39 g/l in
      rabbits treated with yohimbine 0.3, 0.6 and 1.2 mg/kg i.v. and then with
      apraclonidine 1% eye drops. In one group of rabbits, the penetration into the
      aqueous humor of Evans blue injected intravenously was also studied. Evans blue
      content in aqueous humor was 0.03 +/- 0.08 mg/100 ml in control rabbits; 0.92 +/-
      0.53 mg/100 ml in placebo rabbits treated by laser; and 0.28 +/- 0.19 mg/100 ml
      in apraclonidine rabbits treated by laser. Apraclonidine eye drops led to a
      decrease in IOP and prevented IOP rise following argon laser application. Placebo
      treated rabbits had a 20% increase in IOP following laser application.
      Apraclonidine-treated eyes showed mydriasis and blanching of the conjunctiva.
      These effects were not affected by pretreatment with dapiprazole or yohimbine. In
      these experiments, the treatment with apraclonidine 1% eye drops completely
      protected the blood aqueous barrier from the disruption caused by laser burning
      of the iris. The protection was less effective when apraclonidine was applied
      after laser burnings.

PMID- 8535955
TI  - Corneal vascularization and opacification during long-term use of dipivefrin.
AB  - Dipivefrin hydrochloride is a lipophilic prodrug for epinephrine hydrochloride,
      allowing lower concentration of the drug to achieve the same intraocular pressure
      lowering effect and having also less harmful effects than epinephrine
      hydrochloride. However, harmful effects have been associated also with the use of
      dipivefrin and here we report of a case of corneal vascularization during long
      term use of dipivefrin.

PMID- 8535956
TI  - Determination of tolerance to tear protein release following a twice a day
      topical application of N,N-dimethyl-2-phenylethylamine HCl.
AB  - In an effort to develop a long-term topically active tear stimulant, it was
      important to determine if tolerance developed following the repeated instillation
      of N,N-Dimethyl-2-phenylethylamine hydrochloride (AF2975) to the albino rabbit
      eye. New Zealand white rabbits were administered AF2975 (0.15%) twice a day (9 am
      and 4:30 pm) for 10 days. The right eye received the drug solution (50
      microliters) and the left eye received an equal volume of the vehicle. Prior to
      dosing and at the end of first and last dose (10 and 60 minutes post-dosing),
      protein secretion was measured with the use of Schirmer tear test strips placed
      under the lower lid of each eye for five minutes. The strips absorbed tears from
      which protein was extracted. Eyes treated with AF2975 showed a statistically
      significant % increase in protein release compared to baseline values. Control
      eyes did not show statistically significant increases over baseline. A comparison
      of % changes from baseline in protein secretion rates after the first and last
      dose showed no significant differences in either treated or control eyes at 10
      and 60 minutes postdosing. These results indicate that tolerance does not occur
      for protein secretion of topically administered AF2975 (0.15%) following a twice
      a day dosing schedule for 10 days to the rabbit eye.

PMID- 8535957
TI  - Ocular concentrations of mitomycin C after extraocular application in rabbits.
AB  - To determine the intraocular concentrations of Mitomycin C (MMC) after
      extraocular application, we used pigmented rabbits and placed sponges soaked with
      MMC under the conjunctiva on top of the intact episclera. First, we soaked the
      sponges with volumes ranging from 0.025 ml to 0.3 ml of the solution containing
      MMC and sampled aqueous humour after 30 minutes. The concentrations, as
      determined by high performance liquid chromatography, did not correlate to the
      amount of MMC given. Then, we soaked the sponges with different concentrations of
      MMC with a volume of 0.1 ml and sampled aqueous humour, vitreous humour and
      sclera after 60 minutes. The concentrations of MMC were higher in the vitreous
      than in the aqueous, and, relative to these values, very high in the sclera.
      These results indicate that the amount of MMC reaching the interior of the eye
      after standard extraocular application may be highly variable, and that the
      concentrations of MMC in the sclera and formed vitreous can be considerably
      higher than in the aqueous humour.

PMID- 8535958
TI  - Availability of 0.3% ofloxacin ointment and solution in human conjunctiva and
      aqueous humor.
AB  - Ofloxacin 0.3% ophthalmic solution or ointment was administered preoperatively to
      13 patients undergoing cataract surgery. Mean drug concentrations in conjunctival
      biopsies were 2.62 and 6.55 micrograms/gm and in aqueous humor samples were 0.36
      micrograms/mL and 0.43 micrograms/mL, for ointment and solution respectively.
      Mean conjunctival concentrations of ofloxacin achieved MIC90 values for 419 gram
      positive and gram-negative organisms previously analyzed.

PMID- 8535959
TI  - Epidermal dipeptide: a new regulatory factor in proliferative vitreoretinopathy.
AB  - Proliferative vitreoretinopathy (PVR) is the most severe complication of retinal
      detachment surgery, occurring approximately in one out of ten operated eyes. The
      proliferation of retinal pigment epithelial (RPE) cells and fibroblasts is a
      cornerstone in the pathogenesis of PVR. Since inhibitory peptides may take a part
      in the feedback mechanism underlying this proliferation, we assessed the effect
      of synthesized epidermal dipeptide, pyroglu-glyOH (EDP), on the proliferation of
      RPE cells and fibroblasts in vitro. The maximum inhibitory effect of EDP on the
      RPE cells was reached at concentrations ranging from 1.07*10(-13) to 1.07*10(-15)
      M. Its inhibitory effect on fibroblasts followed a similar pattern at all
      concentrations applied, 1.07*10(-6) to 1.07*10(-15) M. These results enhance the
      possibility that PVR may be due to an imbalance of inhibition/disinhibition
      mechanism under participation of several regulatory molecules like EDP. EDP might
      have the potential for reducing the risk of PVR.

PMID- 8535960
TI  - Role of cyclic AMP in prostaglandin mediated responses in the neural retina.
AB  - Exogenous prostaglandins (PGs) have been shown to inhibit dopamine (DA) release
      from the rabbit retina via an effect on presynaptic EP3-receptors. In the present
      study, we investigated the possible involvement of cyclic AMP in DA release and
      in the prostanoid receptor mediated regulation of DA release from the neural
      retina. Both forskolin and 8-bromo-cyclic AMP enhanced field stimulation-evoked
      [3H]DA release from isolated, superfused rabbit retinas without affecting basal
      tracer efflux suggesting that presynaptic cyclic AMP may be involved in the
      pathway leading to DA release. Forskolin attenuated inhibition of evoked [3H]DA
      release caused by low but not high concentrations of PGE2. Both PGE2 and
      sulprostone had no significant effect on basal cyclic AMP levels but inhibited
      forskolin-stimulated cyclic AMP formation. Furthermore, sulprostone was more
      potent than PGE2 in attenuating forskolin-activated cyclic AMP production. The
      inhibition of forskolin-elevated cyclic AMP levels caused by PGE2 was, however,
      unaffected by the EP1-receptor antagonist, AH6809. We conclude that the
      regulation of DA release by presynaptic prostanoid EP3-receptors may be mediated,
      at least in part, through an inhibitory effect on adenylyl cyclase.

PMID- 8535961
TI  - Distribution of salicylate in pigmented rabbit ocular tissues after application
      of a prodrug, sodium monomethyl trisilanol orthohydroxybenzoate: in vivo and ex
      vivo studies.
AB  - SMB (sodium monomethyl trisilanol orthohydroxybenzoate) is an organic complex of
      silicium and salicylate and the main component of a collyrium used in lens
      transparency abnormalities. Biotransformation and penetration of salicylate in
      the whole eyeball have been investigated in vivo after repeated instillations of
      those 14C-radiolabeled eyedrops. We also studied more accurately the salicylate
      diffusion within the lens under ex vivo conditions. In vivo experiments
      demonstrated that 8 to 48 hours after the last instillation, radioactivity was
      detectable in most tissues and remained stable except in the chorioretina. The
      following gradient of distribution was observed: conjunctiva > cornea > iris
      ciliary body > chorioretina > lens > vitreous body > aqueous humor >> plasma and
      blood. The diffusion of the radiolabeled compound in lens fibres was low, but a
      more important retention was observed in lens capsule. Though salicylate
      metabolizing activities have been demonstrated in ocular tissues, no
      biotransformation could be detected under our experimental conditions. The lens
      SA-biotransformation activity was reported to be low and we can most probably
      consider that, in our ex vivo pharmacokinetic study, the lens metabolite amounts
      were negligible compared with the salicylate levels. Under such conditions,
      results showed that the salicylate reached a steady-state between 6 and 12 hours
      of incubation, characteristic of a passive diffusion mechanism. Quantitative
      image analysis of lens section autoradiograms revealed a more intense labeling of
      the anterior part of the lens and suggests that the lens epithelium may
      facilitate the salicylate diffusion. Furthermore, renal excretion is important
      since 40% of the administered eyedrops were eliminated during the study period.

PMID- 8535962
TI  - Fiber orientation of posterior cruciate ligament: an experimental morphological
      and functional study, Part 2.
AB  - The posterior cruciate ligament (PCL) can be anatomically divided into three
      bundles: anterolateral, posteromedial, and posterior oblique. The changes in
      distance between the femoral and tibial attachment sites of these three bundles
      were measured in 10 human knee specimens with intact ligamental structures. The
      femoral to tibial distance (and thus the length) of the posterior oblique bundle
      remained nearly the same throughout flexion between 0 degrees and 90 degrees. The
      femoral to tibial distance of the anterolateral and the posteromedial bundles
      distinctly changed throughout the same range of motion. For a truly functional
      replacement of the PCL, correct isometric placement of the transplant is
      especially important. Based on the results of the present study, an isometric
      reconstruction of the PCL is achieved by positioning the graft within the
      original attachment site of the posterior oblique bundle.

PMID- 8535963
TI  - The menisco-femoral ligaments.
AB  - The menisco-femoral ligaments were studied in 60 knees from 30 dissecting room
      cadavers. The anterior horns of the menisci were attached to the intercondylar
      area of the femur by discrete antero-medial or antero-lateral menisco-femoral
      ligaments, separate from the anterior cruciate ligament, in 15% of knees for each
      meniscus, more frequently than previously appreciated; these anterior horn
      ligaments may exacerbate a meniscal tear. The posterior horn of the lateral
      meniscus was connected with the intercondylar area of the femur in 100% of knees.
      In 93% of knees a ligament ran behind the posterior cruciate ligament while in
      33% of knees a ligament ran in front of the posterior cruciate ligament. We
      propose renaming these the pre-cruciate postero-lateral menisco-femoral ligament
      and post-cruciate postero-lateral menisco-femoral ligament, respectively, to
      avoid confusion with the ligaments of the anterior horns. The menisco-femoral
      ligaments may function in controlling movement of the menisci, especially during
      rotation of the knee. The posterior horn of the medial meniscus has no direct
      femoral attachment and this may be a factor in the increased risk of injury to
      this meniscus.

PMID- 8535964
TI  - Topographical relations between the posterior cricothyroid ligament and the
      inferior laryngeal nerve.
AB  - The posterior cricothyroid ligament and its topographic relation to the inferior
      laryngeal nerve were studied in 54 human adult male and female larynges. Fourteen
      specimens were impregnated with curable polymers and cut into 600-800 microns
      sections along different planes. Forty formalin-fixed hemi-larynges were
      dissected and various measurements were made. The posterior cricothyroid ligament
      provides a dorsal strengthening for the joint capsule of the cricothyroid joint.
      Its fibers spread in a fan-like manner from a small area of origin at the cricoid
      cartilage to a more extended area of attachment at the inferior thyroid cornu.
      The ligament consists of one (7.5%) to four (12.5%), in most cases of three
      (45.0%) or two (35.0%), individual parts oriented from mediocranial to latero
      caudal. The inferior laryngeal nerve courses immediately dorsal to the ligament.
      In 60% it is covered by fibers of the posterior cricoarytenoid muscle, in the
      remaining 40% it is not. In this latter topographic situation there is almost no
      soft tissue interposed between the nerve and the hypopharynx. Therefore, the
      nerve may be exposed to pressure forces exerted from dorsally. It may be pushed
      against the unyielding posterior cricothyroid ligament and suffer functional or
      structural impairment. Probably, this mechanism may explain some of the laryngeal
      nerve lesions described in the literature after insertion of gastric tubes.

PMID- 8535965
TI  - A quantitative ultrastructural study of collagen fibrils in human skin, normal
      scars, and hypertrophic scars.
AB  - The diameter-distribution of collagen fibrils in the dermis of human skin and
      scar tissue has been investigated. In samples of normal skin, normal scar, and
      hypertrophic scar, prepared for transmission electron microscopy, collagen
      fibrils were systematically random-sampled and their diameters measured. There
      was a statistically significant difference between the diameter-distribution of
      fibrils in the papillary and reticular layers of dermis in normal skin. A similar
      pattern was found in normal scar, but not in hypertrophic scar.

PMID- 8535966
TI  - Variations in the lumbosacral ligament and associated changes in the lumbosacral
      region resulting in compression of the fifth dorsal root ganglion and spinal
      nerve.
AB  - Sixty-five lumbosacral regions from adult cadavers were dissected and the
      position and relations of the lumbosacral ligament noted. The lumbosacral
      ligament was present in all specimens; in 22 (34%) it extended medially across
      the ventral ramus of the fifth lumbar nerve, and in six (9%) of these the
      underlying nerve was compressed and visibly flattened. On two of these specimens
      the nerve, together with its dorsal root ganglion, was removed, processed, and
      stained with Masson's trichrome. The compressed nerve showed increased thickness
      of endoneurial and perineurial connective tissue, and the cells of the dorsal
      root ganglion were smaller and surrounded by increased connective tissue,
      particularly at the periphery of the ganglion. Observation of the lumbosacral
      ligament and surrounding anatomical structures suggests that anatomical variation
      in this region may be attributed to the health of the lumbosacral articular
      elements. In those specimens showing compression of the fifth lumbar spinal nerve
      there was also narrowing of the lumbosacral interspace. In these the disc itself
      was compressed and showed degenerative changes. The articular processes at the
      lumbosacral joint were irregular, with thinning and fissuring of the artiuclar
      cartilage. It is suggested that the processes which lead to the further
      development of the ligament, by the formation of additional fibrous bands, are
      mechanical in nature and result from instability at the lumbosacral region
      itself. Instability subsequently leads to the initiation of a chain of
      degenerative changes, involving pathology at the lumbosacral disc and
      zygapophyseal joints.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535967
TI  - The size of the anterior spinal artery in relation to the arteria medullaris
      magna anterior in humans.
AB  - We studied the anterior spinal artery (ASA) in 25 cadaveric human spinal cords to
      determine the cross-sectional area of the ASA cephalad and caudal to the entry of
      the arteria medullaris magna anterior (AMMA). Spinal cords were removed en bloc
      and latex was injected into the AMMA. The preparations were then fixed in
      formalin, embedded in paraffin, sectioned, mounted, and stained with hematoxylin
      and eosin. The diameter and cross-sectional area of the ASA 1 cm above and 1 cm
      below the entry of the AMMA were measured. The mean radius of the ASA above the
      entry of AMMA was 0.14 +/- 0.03 mm compared to 0.28 +/- 0.05 mm below the entry
      of the AMMA (P < 0.001). According to Poiseuille's equation, the resistance to
      blood flow in the ASA cephalad to the AMMA would be 14.8 times greater than the
      resistance to blood flow caudal to the AMMA. This resistance could affect the
      distribution of blood flow in the distal spinal cord whenever flow in the AMMA or
      distal ASA is altered.

PMID- 8535968
TI  - Relative position of porion and tragus in orthodontic patients.
AB  - In order to assess the relationship between the hard (porion-orbitale) and soft
      (tragus-orbitale) tissue Frankfurt planes, the relative positions of porion,
      orbitale, and tragus were evaluated on cephalometric radiographs. A 5-mm
      radiopaque disk was fixed on the right tragus of 160 white orthodontic patients
      (65 males aged 7 to 28 years, and 95 females aged 7 to 36 years), and a pre
      treatment lateral cephalometric radiograph was taken. In every film the positions
      of orbitale, porion, and tragus were digitized, and the linear distances between
      the points, as well as the position of tragus relative to the skeletal
      structures, were calculated. The linear distances porion-orbitale and tragus
      orbitale progressively increased with age, with a low variability in all age
      classes. The linear distances were always larger in the males than in the
      females. The tragus was always lower and more anterior than the porion, with
      vertical distances ranging from 1.2 to 19.8 mm. When the porion-tragus distance
      was expressed as a percentage of the porion-orbitale distance, the variability
      decreased. In the age classes, mean percentage horizontal projections from porion
      ranged from 18 to 23% of the porion-orbitale distance, mean percentage vertical
      projections ranged from 8 to 15%. Unfortunately, sample variability was large,
      and, in a single patient, the position of tragus relative to the skeletal
      structures could be predicted only with a large approximation.

PMID- 8535969
TI  - Styloid chain ossification: report of a case with articulations.
AB  - A bilateral ossified stylohyoid ligament was observed in a cadaver specimen. On
      the left side, the stylohyoid chain was markedly enlarged. The stylohyoid
      ligament was completely ossified into two segments separated by a diarthrodial
      like joint. An articulation was also observed between the enlarged styloid
      process and the ossified ligament. On the right side, the styloid process had a
      normal appearance. The middle part of the stylohyoid ligament was ossified and it
      was attached to the styloid process and to the hyoid bone by a fibrous band.
      Proposed theories to account for the ossification of this ligament are discussed.
      Since the presence of an enlarged and ossified stylohyoid chain can cause much
      discomfort and pain, a greater understanding of the causative factors responsible
      for this anomaly is needed to provide for more effective diagnosis and treatment.

PMID- 8535971
TI  - Vascular anatomy of the spleen.

PMID- 8535970
TI  - Removal of the brain for teaching and examination.
AB  - The brain was removed from cadavers using a modified technique involving
      additionally the removal of most of the squamous occipital bone and laminae of
      the upper cervical vertebrae. The resulting specimens were superior to the usual
      ones in that the medulla oblongata, the upper spinal cord, and all the cranial
      nerves and cerebral arteries were intact. Fears of slow-virus contamination and
      legislative changes are precluding the use of brains obtained in the necropsy
      room for neuroanatomy teaching, so it is paramount that complete brains are
      removed from dissecting room cadavers. The method described herein takes a little
      longer than the traditional method, but is within the capability of an anatomy
      technician and yields better specimens for use in teaching and examinations.

PMID- 8535973
TI  - MSG gene cluster encoding major cell surface glycoproteins of rat Pneumocystis
      carinii.
AB  - The MSG genes of Pneumocystis carinii encode major cell surface glycoproteins of
      multi-gene families and play crucial roles in the pathobiology of P. carinii
      pneumocystosis. The 11,370-bp chromosomal DNA encoding MSG was cloned and
      sequenced. It contained three open reading frames in tandem repeat, MSG99, MSG100
      and ORF-3. MSG99 and MSG100 shared 39% protein sequence identity and belonged to
      the same MSG family, regardless of the internal ca. 1,000-bp deletion in MSG99.
      ORF-3 encodes a putative 47,820-Da protein and had no sequence similarities to
      MSG molecules or any known proteins. However, the ORF-3 protein was rich in
      proline residues and highly hydrophilic except for the C-terminal region, which
      seemed to be an anchoring sequence in the cell membrane. Northern and Southern
      blot hybridization analyses revealed a 3-kb ORF-3 transcript as well as multiple
      DNA fragments carrying the MSG and ORF-3 sequences. These results strongly
      suggested that diverse MSG genes are clustered in tandem repeats and these
      clusters involve ORF-3. The possible association of ORF-3 protein in the cell
      membrane is discussed.

PMID- 8535972
TI  - Nucleotide sequence and features of the Bacillus licheniformis gnt operon.
AB  - Bacillus licheniformis was able to utilize gluconate as the sole carbon source as
      efficiently as Bacillus subtilis did. Southern analysis indicated that B.
      licheniformis likely possesses only one gnt determinant. The nucleotide sequence
      (6278 bp) of the B. licheniformis DNA containing the gnt operon was determined,
      revealing the five complete open reading frames (ORF; genes). The putative
      product of the first gene, oug, did not show any significant homology to known
      proteins, but those of the second to fifth genes exhibited striking homology to
      the gntRKPZ genes of B. subtilis, respectively, indicating that they are the
      corresponding gnt genes of B. licheniformis. Not only is the organization of the
      gnt genes of these two Bacilli highly conserved, but so are the cis regulatory
      elements of their gnt operon. Sequence analysis of the upstream regions of these
      two gnt operons implied that a chromosome rearrangement in B. subtilis might have
      occurred immediately upstream of the gnt operon during evolution, causing it to
      diverge from a common ancestor into B. licheniformis and B. subtilis.

PMID- 8535974
TI  - Novel mouse microsatellites: primer sequences and chromosomal location.
AB  - Sixty-nine sequences containing microsatellites were determined by analysis of
      clones from a pUC118 library of total genomic mouse DNA. These sequences were
      examined for size variation using polymerase chain reaction and gel
      electrophoresis. Fifty-one of them showed allelic variations between C57BL/6 and
      MSM, the two strains used for genetic mapping. Hence, their chromosomal location
      was determined using a panel consisting of 131 backcross mice that had been typed
      with 85 anchor loci. The microsatellites were distributed to most chromosomes
      except for chromosomes 16 and 19. These novel markers with defined locations are
      useful in linkage and genome mapping studies.

PMID- 8535975
TI  - Tissue-specific expression of the gene encoding a mouse RNA binding protein
      homologous to human HuD antigen.
AB  - We have cloned and sequenced cDNAs encoding a mouse RNA-binding protein that is
      homologous to human HuD antigen. The amino acid sequence deduced from the
      nucleotide sequence has revealed that the mouse HuD protein is identical to the
      human counterpart except for two amino-acid substitutions outside the three RNA
      recognition motifs (RRMs) and a difference in the N-terminus. The mouse HuD gene
      produces two major brain-specific mRNAs (3.7 kb and 4.4 kb) and a minor testis
      specific mRNA (1.3 kb), which is indicative of alternative RNA processing. These
      results suggest that the mouse HuD homolog is a member of the tissue-specific RNA
      binding protein family, possibly involved in RNA metabolism in the nervous
      system.

PMID- 8535976
TI  - A novel expression vector for the cyanobacterium, Synechococcus PCC 6301.
AB  - A cyanobacterial expression vector was constructed using ribulose-1,5
      bisphosphate carboxylase/oxygenase (RuBisCO) promoter and terminator sequences
      derived from Synechococcus PCC 6301. recombinant plasmid, designated pARUB19, has
      an ampicillin-resistant (ApR) gene as a selectable marker and four unique
      restriction sites to allow the insertion of foreign genes. Using this vector, the
      luciferase gene from the firefly, Photinus pyralis, was introduced into
      Synechococcus PCC 6301 cells. The luciferase expression vector could be
      maintained stably in the host cells. Light production of luciferin/luciferase was
      detected in the transformants. Luciferase amounted to 1.2% of the total soluble
      protein. This plasmid may facilitate higher levels of foreign gene expression in
      Synechococcus PCC 6301.

PMID- 8535977
TI  - Stability of YACs containing ribosomal or RCP/GCP locus DNA in wild-type S.
      cerevisiae and RAD mutant strains.
AB  - About 2% of human YAC clones, including tandemly repeated segments color vision
      pigment DNA, ribosomal DNA and alphoid DNA have been reported to be inherently
      unstable in yeast hosts, producing more stable deletion products. YACs containing
      color vision red pigment gene DNA or 1.5 rDNA tandem repeat units were
      transformed into hosts bearing lesions at the RAD1, RAD6, RAD51, or RAD52 loci.
      YACs susceptible to deletion during outgrowth of wild-type cells (or in
      preliminary experiments, in RAD6 transformants) were stable for up to 100
      generations or more in the other strains. Thus both the RAD1 and RAD51/RAD52
      epistatic pathways are apparently involved in the instability of YACs containing
      tandem repeat loci, presumably during recombination-based deletion formation; and
      a yeast host disarmed in these pathways will likely maintain YACs intact that are
      otherwise unstable.

PMID- 8535978
TI  - The cost of sedating and paralyzing the critically ill patient.
AB  - The cost of health care is consuming an ever-increasing amount of United State's
      gross domestic product. It is estimated that 15% of health care dollars are spent
      in the ICU. Drugs used in the ICU account for approximately 10 to 15% of costs.
      Many of the sedatives, analgesics, and neuromuscular blocking agents have high
      acquisition and indirect costs. Educating ICU practitioners on cost issues and
      key indications for these drugs not only may help with cost containment in the
      ICU but also can improve patient care.

PMID- 8535979
TI  - Patients requiring sedation.
AB  - Recent advances in the pharmacology of sedative drugs have expanded their use in
      the intensive care unit. Indications and endpoints for sedation, however, often
      are defined poorly and are difficult to assess. Nevertheless, the complications
      of sedative drug administration are real. New indications for sedation have been
      proposed in recent years, including enforcing sleep/wake cycles, manipulating
      cellular metabolism, and preventing myocardial ischemia. The evidence supporting
      the efficacy of these new indications is not yet complete.

PMID- 8535980
TI  - Methods for monitoring the level of sedation.
AB  - Sedative drugs commonly are titrated to effect in critically ill patients.
      Subjective clinical assessment tools are used to determine the patient's level of
      sedation, and there clearly is a need for improved quantitative methods of
      monitoring sedation. This article describes the current methods for assessing the
      level of sedation in critically ill patients and discusses the potential role of
      neurophysiologic monitoring using processed electroencephalograms and evoked
      potentials.

PMID- 8535981
TI  - Optimal intravenous dosing strategies for sedatives and analgesics in the
      intensive care unit.
AB  - Achieving and maintaining adequate levels of analgesia and sedation in critically
      ill patients is a fundamental part of ICU care. Understanding the clinical
      pharmacology of commonly used sedative agents (e.g., midazolam, lorazepam, and
      propofol) and opioids (e.g., fentanyl and morphine) enables clinicians to best
      dose these drugs to the desired clinical effect while minimizing the risk of
      excessive sedation and cardiopulmonary depression. This has significant safety
      and cost implications for patient care in the ICU. Simulations of plasma
      concentrations of these medications when administered to ICU patients provide
      useful insight into the clinical pharmacology of these agents. A number of points
      should be made with regards to the interpretation of these predicted plasma
      concentrations, however. First, it is important to remember that PK parameters
      for most of these agents, with the exception of midazolam and propofol, were
      derived from bolus or short-term infusions administered to healthy patients, and
      that the PK parameters for lorazepam, fentanyl, and morphine when administered as
      long-term infusions to critically ill patients may vary dramatically from these
      initial estimates. Specifically, their volumes of distribution and elimination
      half-lives may prove to be significantly larger and longer, respectively, when
      administered to patients in the ICU. This pharmacokinetic variability may result
      in even longer emergence times than predicted herein following discontinuation of
      continuous infusions of these agents. Until similar studies in ICU patients are
      performed for lorazepam, fentanyl, and morphine, the clinical pharmacology of
      these agents in ICU patients remains uncertain. Additionally, midazolam and
      morphine both have active metabolites that can accumulate in critically ill
      patients receiving long-term infusions. These metabolites add significantly to
      the sedative effects of the primary compound. Other drugs with sedative effects
      given concurrently with any of these agents (i.e., psychotropic agents, epidural
      opioids, etc.) may also contribute to the sedative effects of these drugs. These
      studies do not account for the development of tolerance (which can occur with
      both benzodiazepines and opioids) or changing kinetic profiles within an
      individual patient over time (i.e., due to changes in volume of distribution,
      protein binding, or clearance). Finally, there is a high degree of interpatient
      variability among critically ill patients, and medication dosing must be tailored
      to individual patients' needs (i.e., one dose does not fit all patients). Given
      the uncertainty of resulting plasma concentrations with long-term administration
      of these medications, the best ways to achieve and maintain optimal levels of
      sedation and analgesia while minimizing the risk of oversedation and side effects
      are to (1) initiate sedation in an incremental fashion until the desired level of
      sedation is achieved, then periodically (i.e., once a day) titrate the infusion
      rate of sedative-hypnotics and opioids downward until the patient begins to
      emerge from the sedative effects of these drugs; and finally gradually increase
      the infusion rate until the desired level of sedation is once again achieved; and
      (2) consider the use of a sedation scale to standardize the level of sedation to
      be maintained (see Table 3). The use of such a scale enables physicians to
      communicate to nursing staff the specific level of sedation to be achieved and
      maintained in an individual patient (i.e., titrate the midazolam infusion between
      0 to 5 mg/hr to maintain a sedation score of 2-3; call MD for inadequate
      sedation, respiratory depression, or hypotension). Achieving optimal sedation and
      analgesia of patients in the ICU requires not only that the choice of
      medication(s) be appropriate for the clinical setting but also that there are
      specific clinical endpoints for the agents used (i.e., light versus deep
      sedation, continuous versus intermittent sedation, sedation with

PMID- 8535982
TI  - Opioids and benzodiazepines.
AB  - Most patients in the intensive care unit experience pain and anxiety, which are
      treated most commonly with an opioid or a benzodiazepine. These compounds are
      effective and have a well-established safety record. With the exception of
      associated respiratory depression, they have a relatively wide therapeutic
      window. New approaches and formulations for opioids and benzodiazepines are being
      used with continued success in the clinical setting.

PMID- 8535983
TI  - Barbiturates, neuroleptics, and propofol for sedation.
AB  - In a modern, hectic, and stressful intensive care unit, sedation is an important
      aspect of care, and every nurse and physician in a critical care setting must be
      familiar with it. This article describes older modalities of sedation, including
      barbiturates and neuroleptics, and compares them to a more recently developed
      drug, propofol.

PMID- 8535984
TI  - Inhalational anesthetics in the intensive care unit.
AB  - Intravenous (IV) sedation is convenient, and many different IV agents are used.
      They are not always effective, however, and there are disadvantages to every
      intravenous agent used in clinical practice. Inhalational anesthetics are a
      useful alternative and have specific advantages. Further technologic refinements
      in the technique of inhalational sedation of mechanically ventilated patients may
      lead to wider clinical applications.

PMID- 8535985
TI  - Advantages and disadvantages of combining sedative agents.
AB  - One advantage of combination sedative therapy is the use of small doses of agents
      from different drug classes to treat concomitant behavioral problems. The
      simultaneous use of multiple sedative agents results in the need for new clinical
      decisions regarding the administration of and weaning from the pharmacologic
      effects of these drugs. This article reviews the current status of research
      regarding combination sedative therapy.

PMID- 8535986
TI  - Sedation of the agitated, critically ill patient without an artificial airway.
AB  - One of the most demanding and stressful situations is management of the agitated,
      unintubated, critically ill patient. Sedation often must be provided without a
      specific diagnosis, and the need for rapid airway control must be anticipated. No
      predictably safe and effective techniques are proven. The experience and skill of
      the physician managing the patient during sedation are the predictive factors for
      the best outcome. Even in expert hands, airway compromise and cardiovascular
      decompensation often occur in these very ill patients. Many techniques for
      sedation have been described. Treatment of pain followed by small boluses of
      intravenous sedative agents is a reasonable initial approach. Benzodiazepines
      have a good safety record and provide good amnesia. Other agents have been used,
      by themselves or in combination. Haloperidol may have a therapeutic advantage in
      the disoriented, agitated patient. Prolonged need for significant sedative
      medication usually mandates a secure airway. Once this is accomplished, the
      requirement for a continuously present airway expert at the bedside is removed.
      The standard for sedating a patient without an artificial airway requires a
      higher level of expertise than sedating a critically ill patient with an
      artificial airway.

PMID- 8535987
TI  - Sedation for the mechanically ventilated patient.
AB  - This article discusses the potential benefits of sedation for the mechanically
      ventilated patient. These benefits include the alleviation of anxiety and pain,
      which may result in a reduction of oxygen consumption. Other advantages include
      improved synchronization of a patient's breathing pattern with ventilator
      settings and better patient care, comfort, and safety. The patient's clinical
      situation, such as respiratory failure caused by right-to-left shunt,
      cardiovascular problems, elevated intracranial pressure, hepatic disease, and
      renal failure, needs to be considered when selecting a sedative agent.

PMID- 8535988
TI  - Use of neuromuscular blocking drugs in the critically ill patient.
AB  - Neuromuscular blocking drugs are used routinely to facilitate the care of
      critically ill patients of all ages. This article addresses current uses and
      concerns about the appropriate administration of these drugs. Several important
      topics are highlighted, including basic physiology of neuromuscular transmission,
      blocker pharmacology, drug selection, monitoring, and future areas of research.

PMID- 8535989
TI  - Complications associated with sedative and neuromuscular blocking drugs in
      critically ill patients.
AB  - Pharmacologic administration of sedatives is used routinely in the care of the
      critically ill to enhance patient comfort and optimize care. Long-term
      administration of NMB drugs is far less frequent but often occurs in patients
      with greater organ dysfunction. The experience of several authors using NMB drugs
      in the ICU is summarized in Table 5. Both classes of drugs have potential
      untoward effects. Some are readily predictable; others are not. NMB drugs enjoy a
      long record of safe, effective use during the perioperative period, but certain
      issues linger in defining appropriate administration to critically ill patients.
      Major concerns focus on the appropriate drug selection and delivery, monitoring,
      and neuromuscular recovery of patients who receive NMB drugs for longer than 24
      hours. The development of myopathy and paresis has been increasingly recognized
      after prolonged use of NMB drugs in the ICU. Further investigation needs to fully
      characterize this process, identify those at risk, and outline a mechanism to
      prevent or limit the injury. Prolonged weakness may occur secondary to changes in
      the basic pharmacology and elimination of NMB drugs in ICU patients.
      Pathophysiologic changes in the nerve, muscle, or neuromuscular junction may also
      play a role in the development of some cases of prolonged weakness or myopathy
      after discontinuation of NMB drugs. Concerns about the potential for direct or
      indirect toxicity of NMB drugs to skeletal muscle and in the CNS remain.
      Resolution of these issues will improve the selection and optimal administration
      of sedative and NMB drugs in the ICU setting.

PMID- 8535990
TI  - The history of the cruciate ligaments: some forgotten (or unknown) facts from
      Europe.

PMID- 8535991
TI  - Late results following proximal reinsertion of isolated ruptured ACL ligaments.
AB  - Between 1982 and 1984, 49 patients with fresh isolated proximal ruptures of the
      anterior cruciate ligament (ACL) were operated on in the Trauma Hospital,
      Salzburg. The operation was performed within 1 week of trauma. The operational
      technique used was proximal reinsertion of the ruptured ACL alone.
      Postoperatively the knee was immobilized for 6 weeks in an above-the-knee plaster
      cast. We were able to re-examine 42 of the 49 patients 5-7 years after injury. In
      addition to a clinical examination, testing with a KT-1000 arthrometer was
      performed. The objective and subjective results we found were evaluated using the
      Lsyholm score and OAK knee evaluation form. We found 12 (29%) absolutely stable
      knee joints. We accepted a KT-1000 result of up to 3 mm as satisfactory, and 81%
      of our patients were in this category. The same percentage (81%) scored between
      85 and 100 points on the Lysholm scale. Only 52% scored over 90 points on the OAK
      form. Subjectively only 6 patients (14%) were dissatisfied with their result.

PMID- 8535992
TI  - Bone imaging after acute knee hemarthrosis.
AB  - Follow-up evaluations were carried out in 84 patients examined 5-8 years after
      sustaining an acute traumatic hemarthrosis of the knee. The initial examination
      performed within 2 weeks of injury had revealed 18 patients with a stable knee
      and 66 with anterior instability. Twelve of the patients underwent anterior
      cruciate ligament reconstruction within 3 months of injury and 11 more did so
      between 1 and 3 years after injury. To document joint deterioration at follow-up,
      bone scintigraphy and conventional anteroposterior, lateral, and tunnel X-rays
      were taken. Medial, lateral, patellofemoral and patellar uptake in bone
      scintigraphy was graded from 0 to 4. Six radiological variables were graded at
      eight different sites. Sixty-three patients (75%) had a positive bone scan and 69
      patients (82%) showed radiological changes. Bone scan and X-ray scores were both
      significantly higher in the reconstructed knees.

PMID- 8535993
TI  - Meniscal healing: a histological study in rabbits.
AB  - Repair of meniscal tears occurs best in the region of the capsular attachment.
      The further the tear from the site of capsular attachment, the less the
      vascularity, and healing becomes dubious. For an evaluation of healing in the
      poorly vascularised zone of the meniscus a histological study was performed in
      rabbits with standard longitudinal incisions in the posterior horn of the left
      medial menisci. In addition a biomechanical investigation of scar strength was
      performed. Three groups of animals were studied: group 1 were allowed to heal
      spontaneously, group 2 were sutured and group 3 were treated with fibrin glue.
      After 6 weeks, macroscopically, 4 out of the 10 menisci in groups 1 and 3
      exhibited incomplete scar formation, whereas all menisci in group 2 looked well.
      This result fell short of statistical significance because 2 menisci in group 2
      had to be excluded due to faulty localisation of the standard injury. In all
      groups the scars contained fundamental elements of healing, such as fibroblasts,
      blood vessels and fibrous material. Repair seemed to be significantly influenced
      by the proliferating synovial membrane. Histologically there was no difference
      between group 1 and 3. In both groups the lesions were filled with a broad strip
      of reparative tissue mostly consisting of plexiform collagenous fibres. Although
      the appearance of the menisci in group 2 was similar, the scar tissue was
      distinctly thinner due to the close adaptation of the wound margins, and the
      vascularity seemed better. In all specimens the tissue located towards the free
      rim of the meniscus showed signs of degeneration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8535994
TI  - The importance of arthroscopy in sports injuries in children and adolescents.
AB  - Within a 3-year period (1985-1988), 60 children and adolescents with knee
      injuries sustained mainly while skiing or playing football (soccer) underwent
      clinical examination, X-radiography and arthroscopy. Nearly all the patients
      still had open epiphyseal plates in the knee region. Arthroscopy revealed more
      severe intra-articular trauma than had been suspected on the basis of clinical
      findings. The skiing injuries most commonly involved anterior cruciate ligament
      tears, whereas injuries of the patellar retinaculum and medial meniscus lesions
      predominated in soccer injuries. On comparison with arthroscopic diagnosis,
      clinical diagnosis was erroneous in about 45%. The most common mistaken clinical
      diagnosis was "medial meniscus tear". Of the 60 knee joints subjected to
      arthroscopy, 40 were severely enough injured to warrant surgery. Only one had
      normal intra-articular findings. The study demonstrates that children and
      adolescents can suffer knee trauma requiring surgery, despite open growth plates.
      Downhill skiing and soccer are particularly risky sports in this respect.
      Therefore, sports injuries involving haemarthrosis are clearly an indication for
      arthroscopy, even in childhood and adolescence. Arthroscopy enables early
      identification of the type and extent of intra-articular trauma and subsequent
      early initiation of appropriate therapy.

PMID- 8535995
TI  - Reconstruction of the posterior cruciate ligament using a new drill-guide.
AB  - In 40 normal cadaver knees from adults (mean age 29 years) the average length of
      the posterior cruciate ligament was 38 +/- 4 mm. The angle between the ligament
      and the long axis of the femur was 43.4 +/- 3 degrees with the knee in full
      extension. We studied the functional importance of different attachments of the
      posterior cruciate ligament. The distance between the central point of the normal
      attachment area on the tibia and the central proximal part of the femoral
      attachment area on the medial femoral condyle was found to change least during
      full range of knee motion. On the basis of the results in the present study we
      suggest some basic principles for a standardized replacement operation for a
      deficient posterior cruciate ligament using a new drill-guide. The drill-guide
      has been used in 14 consecutive patients (mean age 26 +/- 6 years) who underwent
      a reconstruction of the posterior cruciate ligament. The patients have been
      followed for 2 years. The Lysholm score increased significantly from 60 +/- 16
      preoperatively to 76 +/- 15 (P < 0.001) at 2 years, and the stability, measured
      with a laxity tester, improved from 8 +/- 3 mm total excursion preoperatively to
      6 +/- 3 mm at 2 years follow-up. The follow-up time is still short but the
      results seem to be promising.

PMID- 8535996
TI  - Bone-ligament interaction in patellar tendon reconstruction of the ACL.
AB  - The bone-ligament junction is one of the most complex biological tissues. Its key
      function is distribution of mechanical loads applied to the ligament in such a
      way as to diminish the concentration of stresses or shearing at the interface.
      This paper reports an experimental assessment of the extent to which a nearly
      normal junction is formed following reconstruction of the anterior cruciate
      ligament (ACL) with patellar tendon in 20 New Zealand white rabbits sacrificed
      after 2-38 weeks. A histological comparison was also made with cadaver ACLs.
      After 5 weeks the new ligament was still separate from the tunnel wall,
      inflammation was no longer present, and there was no junction tissue. A thin
      fibrocartilage layer was observed between the bone and the ligament after 12
      weeks and was thicker 6 weeks later. After 28 weeks, there was a substantial
      layer of fibrocartilage. The new junction was virtually "physiological" by the
      38th week, with all four layers present. Many fibrocartilaginous cells were also
      visible between the collagen fibres. The bone-ligament insertion was almost
      normal. These findings indicate that tendon reconstruction results in the
      formation of a structure very similar to a physiological junction, and thus
      ensures better load distribution over a greater ligament insertion area.

PMID- 8535997
TI  - In vitro load transmission in the canine knee: the effect of medial meniscectomy
      and varus rotation.
AB  - The purpose of this study was to determine the in vitro load-transmission
      characteristics of the canine knee, paying particular attention to the
      positioning effect of the meniscus in the coronal plane. The intact joint was
      first loaded and then tested under two different loading conditions after a
      complete medial meniscectomy. The first set of test conditions attempted to
      simulate those used by previous investigators, by ignoring the spacer effect of
      the meniscus. The second set of tests were carried out following varus rotation
      of the joint (to account for the loss of the meniscal spacer) to assure initial
      contact in both tibiofemoral compartments at the start of test cycle. It is
      presumed that this varus realignment occurs during weight bearing following
      meniscectomy in vivo. As in previous studies, the joints experienced slightly
      larger displacements (although not statistically significant) and had lower
      stiffness values following medial meniscectomy than when intact. However,
      following varus realignment of the joint after meniscectomy, the displacement was
      markedly smaller (-35% to -49%; P < 0.01) and the structural stiffness was much
      greater (47-123%; P < 0.05) over the range of forces analyzed, compared with the
      intact joint. The ratio of dissipated to input energy was 42% for the intact
      joint, and increased following meniscectomy to 54% (P < 0.05) with realignment
      and 55% (P < 0.05) without realignment. Measured contact area decreased by 17% (P
      < 0.05) following meniscectomy alone, and by 12% (P < 0.05) following
      meniscectomy with realignment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8535998
TI  - Unusual patterns of glenohumeral joint injuries in adolescent ski-jumpers.
AB  - We report on two 16.5-year-old ski-jumpers who sustained unusual glenohumeral
      joint injuries. The first fell on landing, the other while running out. Neither
      could give any indications as to the pathomechanics of the injuries, thus
      illustrating the high speed nature of the trauma.

PMID- 8535999
TI  - A comparison of pre-operative evaluation of anterior knee laxity by dynamic X
      rays and by the arthrometer KT 1000.
AB  - The comparison of bilateral dynamic X-rays in passive anterior and posterior
      drawer with a load of 9 kg, and the arthrometer KT 1000 measurements obtained
      from 100 patients before anterior cruciate ligament reconstruction, confirms the
      good diagnostic efficiency of the following methods: (1) radiological measurement
      of the anterior translation of the medial compartment, as an absolute value and
      especially as a differential value in relation to the opposite, uninjured knee,
      the normal value limits being respectively 5 and 2 mm; and (2) arthrometric
      measurement of the maximal manual translation, also as absolute and differential
      values, the normal value limits being 10 and 2 mm respectively. These two
      measurements have a predictive value of 90%. No numerical equivalency exists
      between the radiological and arthrometric values, but their variations in
      relation to each other are statistically correlated. The arthrometer, simple to
      use and totally innocuous, is an excellent test device for consultation, while
      dynamic X-rays allow separate studies of each compartment to look for lesions of
      the posteromedial or posterolateral corners.

PMID- 8536000
TI  - Diagnosis of an ACL disruption with KT-1000 arthrometer measurements.
AB  - The KT-1000 was used to measure anterior tibial displacement in three
      populations: normal subjects (n = 120), patients with unilateral acute anterior
      cruciate ligament (ACL) disruptions (n = 105), and patients with chronic
      unilateral ACL disruptions who were scheduled for ACL reconstructions (n = 159).
      All patients with ACL disruptions were measured with and without anesthesia.
      Tibial displacement under three loading conditions was measured: 89-N anterior
      displacement force, manual maximum displacement force, and quadriceps contraction
      to lift the leg. The measurements of the normal knee in the injured populations
      were not significantly different from those of the knees in the normal population
      on any test. The injured knee tested with and without anesthesia was
      significantly different from the normal knee on all tests. The right-left
      difference in the normal population as less than 3 mm in 98% of patients in the
      89-N test, 97% in the manual maximum test, and 99% in the quadriceps active test.
      The largest amount of displacement and the greatest difference in displacement
      between the injured and the normal knee was produced by the manual maximum test.
      The manual maximum injured-minus-normal knee displacement was 3 mm or more in 99%
      of patients with chronic ACL disruptions and in 95% of patients with acute ACL
      disruptions.

PMID- 8536001
TI  - The bone-ligament junction: a comparison between biological and artificial ACL
      reconstruction.
AB  - The physiological bone-ligament junction is composed of four zones: ligament,
      fibrocartilage, calcified fibrocartilage and bone. It plays a very important part
      in the distribution of mechanical loads applied to ligaments so as to diminish
      stress concentration or shearing at the interface. This paper examines types of
      bone and neoligament insertion after anterior cruciate ligament (ACL)
      reconstruction with a Dacron prothesis, the Leeds-Keio scaffold ligament (LK),
      patellar tendon with LAD augmentation (PT+LAD) and bone patellar tendon bone
      alone (PT). The anterior cruciate reconstructions were implanted in 16 sheep via
      double-isometric bone tunnels without postoperative knee immobilization.
      Histological examination of the new insertions (using haematoxylin-eosin, Giemsa,
      Masson, and Mallory stains) was performed following animal sacrifice after 2, 3,
      6 and 9 months. A layer of fibrocartilage between the bone and the ligament was
      observed with PT, followed by a nearly normal insertion after 6 months. With PT,
      followed by PT+LAD, the augmentation was surrounded by fibrous tissue (also noted
      inside the LAD). The PT insertion was virtually physiological after 3-6 months.
      With the LK scaffold, fibrous tissue was noted in and around the scaffold, even
      after 6 and 9 months. With the Dacron prosthesis, fibrous tissue around the
      ligament was unaccompanied by ingrowth into the prosthesis. Nerve endings
      (pacinian corpuscles) were only present in the PT. These findings show that even
      after 9 months artificial ligaments are separated from bone by fibrous tissue and
      devoid of the histological and biomechanical features of a physiological
      junction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536002
TI  - Prospective long-term results of operative treatment in primary dislocation of
      the patella.
AB  - Among 53 prospectively studied patients who had undergone operative treatment of
      primary patellar dislocation, 9 (17%) suffered recurrence within an average
      follow-up of 6.5 years. All the redislocations occurred in female patients. The
      patients with recurrence also suffered first-time patellar dislocation in their
      unoperated knee during the follow-up significantly more often (P < 0.01) than the
      patients with stable knees. Patients with redislocations were more often
      dissatisfied with their outcome than the stable group, mainly because of annoying
      anterior knee pain (P < 0.05). Preoperatively the patients with redislocation had
      had more pronounced pathological patellofemoral congruity (Laurin's projections)
      in both the operated knee (P < 0.05) and the, at the time uninjured, control knee
      (P < 0.05). To improve the results of operative treatment for acute patellar
      dislocation, surgery should be aimed at correcting the underlying pathology. In
      grossly and symmetrically pathological cases of patellofemoral articulation, a
      distal realignment procedure should be considered. Otherwise conservative
      treatment may be justified.

PMID- 8536003
TI  - Meniscus bucket-handle fixation with an absorbable Biofix tack: development of a
      new technique.
AB  - The authors present a new method for fixation of meniscus bucket-handle lesions.
      This technique is based on the development of a Biofix self-reinforced polylactic
      acid tack and an application system. The main goal of this technique has been to
      eliminate or at least reduce the risk of neurovascular injury during meniscus
      fixation and to simplify the fixation procedure. Additional skin incisions and
      exposure of the knee joint capsule are superfluous. The steps in the development
      of this technique are outlined and the surgical technique and preliminary results
      described.

PMID- 8536004
TI  - Discoid medial meniscus: report of a case treated by arthroscopy.
AB  - A complete discoid medial meniscus with a longitudinal tear was found in a 41
      year-old man and treated by arthroscopy. The symptomatology was characterized by
      a sharp pain corresponding to the medial joint line, slight intrarticular
      effusion without locking or loss of motion. A review of the literature is
      described.

PMID- 8536005
TI  - Sacral osseous destruction in a female gymnast: unusual manifestation of
      Scheuermann's disease?
AB  - We describe a 14-year-old female gymnast whose complaint was that of chronic low
      back pain. Radiographs and computed tomograms showed both lumbar manifestations
      of Scheuermann's disease and an osseous destruction of the S1 vertebral body. We
      suggest that this is a sacral component of Scheuermann's disease.

PMID- 8536007
TI  - Autograft meniscus replacement: experimental and clinical results.
AB  - Because of the risks related to allograft meniscus replacement an attempt was
      made to replace the medial meniscus by autograft tissue. In animal experiments
      the free middle third of the patellar tendon was transformed to a meniscus-like
      structure within one year after insertion. Early arthroscopic results after
      autograft meniscus replacement in a clinical series comprising 20 patients are
      promising.

PMID- 8536006
TI  - Arthroscopic Bankart procedures for anterior shoulder instability. A review of
      the literature.

PMID- 8536008
TI  - Lower leg overuse injuries in athletes.
AB  - Achilles paratenonitis and medial tibial syndrome are the most common specific
      overuse injuries among athletes in Finland, and they are a problem especially in
      endurance sports, such as long-distance running and jogging. Conservative
      treatment is often successful, but if it fails operative treatment is necessary.
      The surgical methods developed in Finland, which are widely used in the treatment
      of Achilles paratenonitis and medial tibial syndrome, are presented with clinical
      follow-up results in this paper. The patients operated on for Achilles
      paratenonitis were some years older than the patients operated on for
      retrocalcaneal bursitis (mean 38.4 versus 32.3 years). Results after operation
      were excellent or good in 92.4% of 291 patients operated on for Achilles
      paratenonitis, 84.2% of the 63 operated on for retrocalcaneal bursitis and 79% of
      the 47 operated on for medial tibial syndrome. All the patients treated
      operatively were patients in whom conservative treatment had failed. In
      conclusion, operative treatment of Achilles paratenonitis or medial tibial
      syndrome in athletes is indicated when these complaints do not respond to any
      type of conservative treatment.

PMID- 8536009
TI  - Surgical treatment of patellar tendinitis.
AB  - Patellar tendinitis is an overuse syndrome affecting the origin of the patellar
      tendon and its underlying part. Ultrasonography is useful to investigate
      tendinous pathology. It describes the anatomical lesions and their extent.
      Surgical excision of irreversible lesions, demonstrated on ultrasonography, is a
      logical attitude which provides good results.

PMID- 8536010
TI  - The use of continuous passive motion after arthroscopically assisted anterior
      cruciate ligament reconstruction: help or hindrance?
AB  - One hundred and eight patients having undergone arthroscopic anterior cruciate
      replacement and having had continuous passive motion (CPM) as part of their
      immediate post-operative regime were prospectively compared with 108 patients
      having an identical operative procedure but not receiving CPM. All patients were
      operated on by the same surgeon, and the two groups were well matched for age,
      weight and associated injuries and procedures. Those not receiving CPM required
      significantly less analgesia (P = 0.0001), had less blood loss measured in the
      drains (P = 0.001) and had a shorter hospital stay (P = 0.0001). At review 6
      months after surgery, there was no significant difference between the two groups
      in the range of movement of the operated leg compared to the normal leg.

PMID- 8536011
TI  - Five-year results of anterior cruciate ligament reconstruction with the Stryker
      Dacron high-strength ligament.
AB  - Forty-two consecutive patients (27 male and 15 female, with a mean age of 26
      years) suffering from unilateral chronic anterior cruciate ligament insufficiency
      underwent surgical reconstruction with a Dacron high-strength ligament (Stryker).
      In 32 patients the synthetic ligament was used as a reinforcement in an
      iliotibial band intra-articular procedure and in 10 patients as an intra
      articular prosthesis without biological reinforcement. There were 24 concomitant
      injuries such as meniscal tears, status post-meniscectomy or medial collateral
      ligament insufficiency at the time of reconstruction. The initial injury occurred
      during soccer in 23 patients and other pivoting sports in 16 patients. Two and 5
      years after reconstruction, the patients underwent clinical examination,
      including the instrumented knee laxity test (OSI), and performed subjective
      evaluation. The anterior tibial translation was 6.3 +/- 2.6 mm greater than in
      the healthy knee, the mean Lysholm score was 78 points, and the Tegner activity
      score was lower than its pre-injury level. Radiography revealed that 31 of 37
      ligaments had ruptured and another 2 ligaments showed more than 5 mm side-to-side
      increased laxity. The Stryker Dacron high-strength ligament ruptured in more than
      80% of the cases and patients could not return to their pre-injury physical
      performance activities.

PMID- 8536012
TI  - In vivo monitoring of circulation in the intact anterior cruciate ligament using
      the laser Doppler flowmeter.
AB  - Laser Doppler flowmetry permits observation of circulation in the microcapillary
      regions of structures under in vivo conditions. We used a laser device
      manufactured by the Swedish company Perimed and a special probe to observe the
      capillary circulation in the anterior cruciate ligament during arthroscopic
      surgery. This produces measured values in millivolts; these values are relative
      in nature and cannot be used to determine an absolute value for capillary
      circulation by volume per unit time. Under standardized conditions, circulation
      measurements and simultaneous recordings with a two-channel recorder were made
      from 11 patients. In all cases, pulsations of the capillary circulation
      synchronous with the heart beat could be seen on three measuring points on the
      anterior cruciate ligament; these disappeared upon complete deprivation of blood
      supply. We found a large individual range of variation in the so-called blood
      cell flux values from 30 to 620 mV. The magnitude of the heart-synchronous
      pulsations ranged between 20 and 240 mV. Only vague linear relationships were
      found (a) between the individual measuring points and (b) between the flux values
      and the magnitude of pulsation; there was no relationship between the flux values
      and blood pressure and/or red blood count (erythrocyte count, hemoglobin,
      hematocrit).

PMID- 8536014
TI  - Electrical stimulation of vastus medialis and stretching of lateral thigh muscles
      in patients with patello-femoral symptoms.
AB  - Thirty patients with unilateral patello-femoral symptoms and a hypotrophic vastus
      medialis muscle were treated with transcutaneous electrical stimulation of the
      vastus medialis obliquus and stretching of the lateral thigh muscles twice daily
      for 10 weeks. Before and after treatment the position of the patella at fixed
      knee flexion angles and the area of the vastus medialis and vastus lateralis
      muscles were studied by computed tomography. Isokinetic quadriceps torque was
      registered with a Cybex II Dynamometer. An evaluation with a functional knee
      score was carried out. The healthy contralateral leg served as control in all the
      examinations. Clinically two-thirds of the patients had improved after 10 weeks
      of treatment and this improvement remained at follow-up 3.5 years later. The area
      of the vastus medialis and the quadriceps torque of the treated leg increased
      significantly, while the area of the vastus lateralis and the position of patella
      did not change. We conclude that transcutaneous electrical muscle stimulation of
      the vastus medialis and stretching of the lateral thigh muscles might be of
      benefit in patients with patello-femoral symptoms and a hypotrophic vastus
      medialis. An improvement after 10 weeks of treatment seems to predict a good long
      term result.

PMID- 8536013
TI  - Does the glenohumeral joint capsule have proprioceptive capability?
AB  - We performed a clinical study examining 60 volunteers with stable shoulder joints
      randomized to two groups. In group 1 we injected 5 ml lidocaine intra
      articularly. In group 2 we injected 5 ml saline with 5 ml contrast dye the same
      way. After the injection we measured the amount of passive anteroposterior
      translation that occurred during anterior and posterior drawer tests and the
      amount of inferior subluxation during downward stress. We documented the extent
      of the passive glenohumeral translation using ultrasound. We had no complications
      related to the intra-articular injection or to the stability measurement. After
      the injection neither group had significant pain, and the patients were not
      apprehensive about the ensuing stability test. In group 1 (lidocaine)
      anteroposterior translation of 13.2 +/- 6.3 mm was seen in the anterior and
      posterior drawer test, whereas in group 2 (no lidocaine) the anteroposterior
      translation was only 6.8 +/- 3.2 mm. The difference between the two groups was
      statistically significant (P < 0.05). With downward stress during the sulcus test
      the distance between the acromion and the humeral head increased by 5.6 mm (+/-
      3.2) in group 1 and by 2.7 mm (+/- 2.1) in group 2. This difference was also
      statistically significant (P < 0.05). Clinical consequences: Taking our
      preliminary findings into account, the capsule of the glenohumeral joint seems to
      have proprioceptive capability. Nerve fibres and mechanoreceptors seem to be
      localized in the capsule tissue, being part of a physiological feedback
      mechanism. If our conclusions proprioceptive capability. Nerve fibres and
      mechanoreceptors seem to be localized in the capsule tissue, being part of a
      physiological feedback mechanism.

PMID- 8536015
TI  - Non-operative treatment of acute medial collateral ligament lesions of the knee
      joint.
AB  - From 1985 to 1990 102 patients with isolated lesions of the medial collateral
      ligament of the knee were managed non-operatively with early protected motion and
      physical therapy. Eighty-six returned to a follow-up examination. The mean follow
      up time was 44.2 months. The knees were stable in all but two cases and showed
      good or excellent results. Ninety-seven percent of the patients returned to their
      earlier activity level.

PMID- 8536016
TI  - Impingement of the rotator cuff in athletes caused by instability of the shoulder
      joint.
AB  - An impingement of the rotator cuff can be caused by chronic anterior instability
      of the shoulder joint. This particular disease is often found in athletes engaged
      in overhead motion in abduction/external rotation of the arm, such as in ball
      sports like volleyball or European handball, racket sports like tennis or
      badminton, or swimming. For those patients that cannot be cured by conservative
      treatment such as muscular stabilization, surgical treatment is indicated:
      anterior reconstruction of the capsule and/or the glenoid labrum, and in addition
      -if necessary--subacromial decompression and revision of the rotator cuff.
      Between October 1988 and April 1992, we operated on 66 shoulders in 64 top
      athletes suffering from chronic anterior or multidirectional instability of the
      shoulder joint that had caused an impingement syndrome of the rotator cuff. In
      all cases, the athlete was unaware of the instability. Conservative treatment had
      been unsuccessful. Surgical treatment was successful in close to 90% of the
      athletes.

PMID- 8536017
TI  - Graft isometricity in unitunnel anterior cruciate ligament reconstruction:
      analysis of influential factors using a radiographic model.
AB  - A radiographic model was developed to investigate the influence of three surgical
      variables on the change in attachment point distance (CAPD) of a hypothetical
      graft using the unitunnel technique of anterior cruciate ligament (ACL)
      reconstruction. Using three different femoral target points, we tested the
      hypothesis that varying the angle of knee flexion between 70 degrees and 110
      degrees and varying the tibial starting point over a 4-cm range do not result in
      a significant variation in CAPD. We also tested the hypothesis that the CAPD from
      0 degrees to 135 degrees is greater than the CAPD from 0 degrees to 90 degrees.
      There was a statistically significant correlation (r = 0.8465, P < 0.0001)
      between radiographically estimated and isometer-measured values of CAPD. The
      tibial starting point and the femoral target point were found to affect the CAPD
      significantly (P < 0.005). A more proximal tibial starting point was associated
      with a lower CAPD. Both the center of the anatomic femoral attachment of the ACL,
      and a point 1 mm medial to the junction of the roof and lateral wall of the
      femoral intercondylar notch and 6 mm anterior to its posterior margin, were
      associated with lower CAPD values than a target point 5 mm superior and posterior
      to the center of the femoral ACL attachment. The angle of knee flexion did not
      significantly affect the CAPD. The CAPD [0 degrees-135 degrees] was significantly
      greater than the CAPD [0 degree-90 degrees] for all combinations of variables (P
      < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536018
TI  - Morphometry of the semitendinosus and gracilis tendons with application to
      anterior cruciate ligament reconstruction.
AB  - The length and cross-sectional area of human semitendinosus and gracilis tendons
      were measured in both single- and multi-strand configurations for the purpose of
      anterior cruciate ligament graft preparation. The average lengths of the
      semitendinosus and the gracilis tendons were 235 +/- 20 mm (mean +/- SD) and 200
      +/- 17 mm, respectively. The cross-sectional area of a doubled semi-tendinosus
      tendon (two strands) was significantly less than that of a 10-mm-wide patellar
      tendon graft (P < 0.001). The cross-sectional area of the tripled semitendinosus
      tendon (three strands) and the 10-mm-wide patellar tendon were similar. Doubling
      of the combined semitendinosus and gracilis tendons (four strands) and tripling
      of this combination (six strands) resulted in a significantly greater cross
      sectional area in comparison to the 10-mm-wide patellar tendon (P < 0.05, four
      strands; P < 0.001 six strands). This investigation demonstrates that anterior
      cruciate ligament grafts fashioned using multiple-strand combinations of the
      semitendinosus and gracilis tendons result in a cross-sectional area that is
      comparable to the bone-patellar tendon-bone graft. This is an important finding
      since cross-sectional area reflects the intra-articular volume of collagenous
      tissue. This information should be helpful to surgeons considering using the
      hamstring tendons as an anterior cruciate ligament graft.

PMID- 8536019
TI  - Reconstruction of the posterior cruciate ligament with LAD-augmented
      semitendinosus and gracilis tendons: a preliminary report.
AB  - We present our technique for reconstruction of the posterior cruciate ligament
      (PCL) using the semitendinosus and gracilis tendons with the Kennedy ligament
      augmentation device (LAD). The safe and excellent exposure of the posterior
      aspect of the knee allowed us to identify the most isometric position in the
      intercondylar notch of the femur. In addition to this advantage, firm fixation of
      the LAD-augmented tendons with staples prevented the tibia from sagging
      posteriorly during early protected motion of the knee. Evaluation of 12 patients
      followed for more than 2 years showed 9 (75%) good results. In this small series
      no correlation was found between clinical results and the number of major
      structures injured, indicating that postoperative care is as important as
      isometric placement of the PCL in obtaining satisfactory results.

PMID- 8536020
TI  - Function of the glenohumeral ligaments in active stabilisation of the shoulder
      joint.
AB  - The joint capsules and the glenohumeral ligaments of 12 human shoulder specimens
      were histologically investigated by light microscopy. Serial sections of 15
      microns thickness were cut. The tissue was stained following the haematoxylin
      eosin and van Giesson techniques. For specific identification of neural elements
      we made use of a special silver impregnation technique, described by Novotny, for
      staining axons in peripheral nerves. Axons of different diameters ranging from
      0.2 microns to 70 microns were discovered within the ligaments. Close to the
      humeral site we found small nerves forming neurovascular bundles. Within their
      connective tissue sheaths, the axons exhibited a serpentine configuration, which
      may give extra length and may allow stretching of the nerve during motion. Most
      of the axons discovered were located in the subsynovial layer of the ligaments.
      In general the diameter of these subsynovial axons did not exceed 10 microns. In
      addition to these axonal structures, we detected nerve endings which can be
      classified according to Freeman and Wyke as type II mechanoreceptors (Pacinian
      corpuscles). These mechanoreceptors had a diameter of approximately 150 microns.
      They were also positioned directly beneath the synovial membrane and close to the
      humeral site of insertion of the ligaments. CLINICAL SIGNIFICANCE: The described
      neural structures in the glenohumeral ligaments are of particular clinical
      importance in the light of the high incidence of recurrent shoulder dislocation
      and concomitant Bankart lesions. The mechanoreceptors located in the glenohumeral
      ligaments may control the stabilising shoulder musculature. On this premise,
      rupture or detachment of these ligaments will lead to a loss of a feedback
      mechanism.

PMID- 8536021
TI  - Patellectomy and osteoarthritis: arthroscopic findings following previous
      patellectomy.
AB  - We reviewed the arthroscopic findings in 16 knees in which a patellectomy had
      been performed 1-47 years previously (average 15.4 years). The study group
      consisted of 13 women and 3 men with an average age of 46.3 years (range 22-64
      years). The knee symptoms had failed to respond to non-operative treatment and
      the treating surgeon (R.J.B.) had determined that arthroscopic examination was
      warranted. Fifteen of the 16 patients had articular cartilage damage,
      particularly in the medial compartment and trochlear groove. The severity of
      articular cartilage damage correlated with time since patellectomy, but not with
      patient age. Apart from the previous patellectomy, no predisposing factors could
      be identified to account for the frequency and severity of tibiofemoral
      osteoarthritis in this relatively young group of patients. Our findings suggest
      that there may be an association between patellectomy and the subsequent
      development of osteoarthritis.

PMID- 8536022
TI  - Isokinetic quadriceps training in patients with patellofemoral pain syndrome.
AB  - The aims of the present investigation were (a) to evaluate the effect of
      eccentric quadriceps training in patients with unilateral patellofemoral pain and
      (b) to compare the effect of eccentric and concentric quadriceps training in
      patients with bilateral patellofemoral pain. Fifteen patients (9 male and 6
      female, aged 17-36 years with a mean of 27.5 years) participated in this study.
      Nine patients had unilateral pain and trained their painful leg eccentrically,
      while six had bilateral pain and trained one leg eccentrically and the other
      concentrically. Quadriceps muscle training was performed on a Kin-Com dynamometer
      at 90 degrees/s and 120 degrees/s angular velocity twice a week for 8 weeks.
      Before and after the treatment period the thigh muscle torques were measured on
      the Kin-Com dynamometer at 60 degrees/s, 90 degrees/s, 120 degrees/s and 180
      degrees/s for quadriceps and at 60 degrees/s and 180 degrees/s for hamstrings.
      Nine controls, matched for gender and age with the group with unilateral pain,
      were tested in the same way on the Kin-Com dynamometer. For functional evaluation
      a knee score was calculated before training, after 8 weeks of training and at a
      mean of 3.4 years after completion of the training. After 8 weeks of training and
      at follow-up times of 1 and 3.4 years the patients were also questioned regarding
      whether or not they felt improvement from the training programme. To determine
      the degree of knee pain during the training Borg's pain scale was used. The
      results showed that, compared with the controls, the patients had a significantly
      lower knee extensor torque in their painful leg at all velocities
      measured.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536023
TI  - Effect of taping the patella on concentric and eccentric torque and EMG of knee
      extensor and flexor muscles in patients with patellofemoral pain syndrome.
AB  - The acute effect of patella taping on torque and electromyographic (EMG) activity
      in maximal voluntary concentric and eccentric action of the knee extensor and
      flexor muscles in patients with patellofemoral pain syndrome was studied in 48
      patients (62 knees). The patients (28 female, 20 male) were tested concentrically
      and eccentrically on a Kin-Com dynamometer with simultaneous EMG recording with
      the patella untaped and medially or laterally taped. Patients with clinically
      normal patellar mobility did not improve their quadriceps performance by taping
      of the patella; after medial taping they decreased their muscle torque during
      concentric work at 60 degrees/s (P < 0.05) and eccentric work at 180 degrees/s (P
      < 0.05). After lateral taping they decreased their muscle torque during
      concentric work at 60 degrees/s (P < 0.05) and eccentric work at both 60
      degrees/s (P < 0.01) and 180 degrees/s (P < 0.05). Moreover, these patients also
      decreased their agonist EMG activity during concentric work at 60 degrees/s (P <
      0.05) and 180 degrees/s (P < 0.05) and their antagonist EMG activity during
      eccentric work at 60 degrees/s (P < 0.01). Patients with a clinical lateral
      patellar hypermobility increased their knee extensor torque after medial taping
      at 60 degrees/s during both eccentric work (P < 0.01) and concentric work (P <
      0.05). The greatest improvement in quadriceps performance, however, was in
      patients with a clinical medial patellar hypermobility. They increased their knee
      extensor torque after lateral taping during eccentric work at both 60 degrees/s
      (P < 0.001) and 180 degrees/s (P < 0.001) and during concentric work at 60
      degrees/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536024
TI  - Personality in patients with long-term patellofemoral pain syndrome.
AB  - Personality characteristics in patients with long-term patellofemoral pain were
      compared to those of matched controls and other groups both of non-patients and
      of psychiatric outpatients with character disorders. Personality was described
      using the self-administered dependency and alexithymia scales, the Karolinska
      Scales of Personality and the Rorschach inkblot method. The hypothesis was that
      the patellofemoral pain patients would have higher levels of anxiety, depression,
      helplessness, aggression and alexithymic characteristics than the matched
      controls. There were only a few significant differences between the knee patients
      and the matched controls. The Rorschach measures suggested significantly greater
      depression, hostility and passive attitude in the knee patients as compared to
      the reference data. There were no indications of the hypothesised alexithymic
      characteristics in the knee patients. If patellofemoral pain patients do not
      improve as expected, referral to a pain clinic with psychological expertise could
      be considered.

PMID- 8536025
TI  - The medial patellofemoral ligament revisited: an anatomical study.
AB  - The purpose of this study was to provide a comprehensive description of the
      anatomy of the medial patellofemoral ligament (MPFL). The anterior and medial
      aspects of 4 unpreserved and 16 preserved cadaveric human knees were dissected
      with particular attention being paid to the relationship of the various layers to
      one another and to the place of the MPFL within these layers. We confirmed that
      the MPFL is a distinct structure lying within layer II. Its bulk varies
      considerably between individuals but not from side to side in a given individual.
      The visualisation, attachments, and gross morphology of the ligament are
      described. The attachments of the MPFL and the orientation of its fibres suggest
      that it may have a role in limiting lateral excursion of the patella. The common
      attachment of the tendon of the vastus medialis muscle and the ligament to the
      superomedial patella suggests that there may be a dynamic element to such a
      stabilising function.

PMID- 8536026
TI  - Bilateral osteochondritis dissecans of the medial trochlea femoris: an unusual
      case of patellofemoral pain.
AB  - We report a case of bilateral osteochondritis dissecans of the medial trochlea
      femoris. Arthroscopic removement of loose bodies in the symptomatic left knee led
      to an excellent result; the untreated right knee showed effusion and locking one
      year later. This condition should be considered in the diagnosis of
      patellofemoral pain.

PMID- 8536027
TI  - Is intra-articular pethidine an alternative to local anaesthetics in arthroscopy?
      A double-blind study comparing prilocaine with pethidine.
AB  - We investigated the per- and postoperative pain-reducing effect of pethidine
      given intra-articularly (i. art.). Thirty patients subjected to knee joint
      arthroscopy, diagnostic and surgical procedures, were randomly assigned to one of
      three groups. Group A consisted of ten patients who received 250 mg prilocaine +
      200 micrograms adrenaline (i. art.) in a volume of 50 ml, group B of ten patients
      who received 200 mg pethidine (i. art.) in 50 ml saline, and group C of ten
      patients who received 200 mg pethidine + 200 micrograms adrenaline (i. art.) in
      50 ml saline. During arthroscopy the patients reported on pain intensity and
      discomfort using visual analogue scales. Ratings were low and did not differ
      significantly between the three groups. Two of three patients in each group
      requested additional analgesics or sedatives due to pain and discomfort, but
      again with no difference between the three groups. Postoperatively all patients
      rated their pain intensity at rest and during movement (at 0, 1, 2, 3, 4, 5, 6,
      12 and 24 h). The patients receiving pethidine (group B) reported significantly
      less pain at rest and movement than group A patients, in general at 1-4 h
      postoperatively. A significant difference was detected between groups B and C at
      4 h postoperatively. Calculating the total sum of pain scores, patients receiving
      pethidine (group B) reported significantly less pain both at rest and during
      movement than those receiving prilocaine (group A). Furthermore, patients in
      group B used significantly less analgesics than those in group A. Adrenaline did
      not potentiate the effect of pethidine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536028
TI  - Range of motion, muscle torque and training habits in runners with and without
      Achilles tendon problems.
AB  - Achilles tendon injuries are common in runners. The aim of the present study was
      to analyse the training programme, any Achilles tendon problems, muscle tightness
      and range of motion of the ankle joint, and concentric and eccentric muscle
      torques of the calf muscles in middle-distance runners with and without Achilles
      tendon problems. Eighty-three middle-distance runners answered a questionnaire on
      their sports background, training habits and any injuries. Thirty-four percent
      had suffered from some type of problem relating to the Achilles tendon. Ten of
      the athletes who had suffered from Achilles tendon problems and ten who had never
      had any Achilles tendon trouble were randomly selected. These 20 runners
      underwent a clinical examination. The range of motion of the ankle joint was
      recorded objectively by a hydraulic and computerised isokinetic dynamometer by
      measuring resistance to passive motion. Concentric and eccentric muscle torques
      of the gastrocnemius-soleus complex were recorded. The runners with Achilles
      tendon problems had trained for significantly more years and covered
      significantly longer distances per week than runners without Achilles tendon
      problems. There were no significant differences in other training methods or in
      best results over 800 m and 1500 m. Runners with Achilles tendon problems had a
      significantly lower range of motion of the ankle joint. They also had
      significantly lower eccentric torques of the gastrocnemius-soleus complex, but no
      differences in concentric torques were found between the groups.

PMID- 8536029
TI  - Ankle injuries in basketball players.
AB  - We carried out a retrospective study of the frequency of ankle sprains in
      basketball players. A questionnaire about previous ankle injuries, time off after
      such injuries, current ankle problems, personal data, number of practice hours
      and the use of prophylactic measures was sent out to 102 basketball players in a
      second division league in Sweden. Ninety-six players answered. 92% of them had
      suffered an ankle sprain while playing basketball, and of these 83% reported
      repeated sprains of one ankle. In the last two seasons, 78% of the players had
      injured at least one ankle. The injury frequency in the investigation was 5.5
      ankle injuries per 1000 activity hours. 22% of the players used some kind of
      prophylactic support of their ankle joints. Because of the great number of ankle
      sprains and the disability in terms of time away from sports that they cause,
      prevention of these injuries is essential.

PMID- 8536030
TI  - Ankle sprain and postural sway in basketball players.
AB  - The present study compares postural ankle stability between previously injured
      basketball players, uninjured players and a control/group. Postural sway was
      recorded and analysed by stabilometry using a specially designed computer
      assisted forceplate. Recordings were obtained for 60 s on each foot. The
      stabilometric results in the players with no previous injuries did not differ
      from those in the controls. Players with a previously injured ankle differed
      significantly from the control group. These players had a larger mean postural
      sway and used a larger sway area.

PMID- 8536031
TI  - Spinal sagittal mobility and joint laxity in young ballet dancers. A comparative
      study between first-year students at the Swedish Ballet School and a control
      group.
AB  - The present study compares spinal configuration, spinal range of motion and joint
      mobility in first-year students of the Swedish Ballet School and in nondancing
      students of corresponding age and sex in a state school. The study comprises all
      the first-year (fourth grade) students (n = 23) at the Swedish Ballet School: 11
      boys and 12 girls. Their dance practice time was 10 h per week. Thirty-six
      children in the fourth grade at a state school comprised the control group. None
      of the controls took ballet classes or participated in organised gymnastics out
      of school. The neutral spine configuration in standing and the sagittal spine
      mobility were measured using Debrunner's kyphometer and Myrin's inclinometer.
      Joint laxity was measured by employing a modified form of the Contompasis method.
      Compared with the controls, the dancers showed a higher incidence of joint
      hypermobility, greater mobility of the thoracic spine, a less prominent lordosis
      of the lumbar spine and a less prominent kyphosis in the thoracic spine in the
      neutral standing position. The dancers had done little or no ballet training
      before entering the ballet school at the age of ten. The results agree with those
      of earlier studies and suggest that increased flexibility is an asset for those
      being selected as future ballet dancers.

PMID- 8536032
TI  - Arthroscopic resection of the acromioclavicular joint (ARAC).
AB  - In 65 patients an arthroscopic resection of the AC-joint (ARAC) was performed.
      The data of 27 male and 24 female patients with a minimum follow-up of 6 months
      were available for analysis. 2 patients had bilateral procedures. Patients with
      rotator cuff tears were excluded from this series. The patients were aged between
      22 and 69 years (average 48.4 years). The mean interval from the onset of pain to
      conservative treatment was 4.6 months and the average period of conservative
      management prior to surgery was 9.8 months. The indication for ARAC was pain
      which interfered with the patients' activities of daily living, work, or athletic
      activities and had not responded to conservative therapy for at least 6 months.
      Patients' data were recorded before and after surgery according to a 100-point
      score as well as with a visual analogue scale. The patients' mean preoperative
      score was 67.8 (+/- 14.6). After surgery, a significant improvement to 93.3 (+/-
      12.3) was achieved. Comparing the different parameters we found significant
      differences in pain during shoulder movement, function, and active range of
      motion. Prior to surgery the other parameters already scored well, so they did
      not serve as good discriminators for these patients. The mean reaction length of
      the lateral clavicle was 23.2 mm inferiorly, 15.9 mm in the middle third, and
      13.1 mm superiorly. No ectopic bone formation or postoperative spurs were
      identified in this series. We could not demonstrate regeneration of the resected
      parts of the lateral clavicle. No major complication was noted.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8536033
TI  - Meniscal nodule.

PMID- 8536034
TI  - Suturing of the meniscus using the Nottingham needle and Ti-cron suture.

PMID- 8536035
TI  - Arthroscopy in patients with knee endoprostheses.
AB  - Remarkable advances have been made in knee replacement. Nevertheless, patients
      and surgeons still face unsolved problems following implantation of an artificial
      knee joint. In some cases arthroscopy may serve as a diagnostic or surgical tool.
      Our experience has shown that arthroscopy is helpful in diagnosing polyethylene
      wear, fractures of prosthetic components and loosening of the endoprosthesis.
      Moreover, surgical procedures can be synchronously performed, e.g. lateral
      release for complete or partial patellar dislocation, parapatellar denervation
      for retropatellar pain and resection of meniscal remnants or a synovial plica in
      case of interposed tissue. In contrast to knee infections, early prosthetic
      infections should be treated with an open procedure.

PMID- 8536036
TI  - Problems with the sterilisation and the maintenance of sterility of arthroscopic
      instruments: a comparison of different types of camera drapes.
AB  - Case reports of gas gangrene following arthroscopy using instruments sterilised
      with glutaraldehyde demonstrate the inadequacy of this sterilisation method. A
      safer way to achieve sterility is to combine gas-sterilised arthroscopes and a
      non-sterile camera covered with a sterile drape. Several different types of
      camera drapes are available; their different safety aspects are discussed.

PMID- 8536037
TI  - Evaluation of knee ligament injuries with the IKDC form.
AB  - Various scoring systems have been proposed to quantify the disability caused by
      knee ligament injuries and to evaluate the results of treatment. None of these
      systems has found worldwide acceptance, mainly because all scoring systems
      attribute numerical values to factors that are not quantifiable, and then the
      arbitrary scores are added together for parameters not comparable with each
      other. For these reasons a group of knee surgeons from Europe and America met in
      1987 and founded the International Knee Documentation Committee (IKDC). A common
      terminology and an evaluation form was created. This form is the standard form
      for all publications on results of treatment of knee ligament injuries. It is a
      concise one-page form. It includes a documentation section, a qualification
      section and a evaluation section. For evaluation there are four problem areas
      (subjective assessment, symptoms, range of motion and ligament examination).
      These are supplemented with four additional areas that are only documented but
      not included in the evaluation (compartmental findings, donor site pathology, X
      ray findings and functional tests). The form can be used pre- and post
      operatively and at follow-up. It has been specified that in any publication the
      minimum follow-up time for short-term results should be 2 years, for medium-term
      results 5 years and for long-term results 10 years. The largest part of the sheet
      is the qualification section. It is called "qualification" section rather than
      "scoring" section because no scores are given. Each parameter is qualified as
      "normal", "nearly normal", "abnormal" or "severely abnormal". This qualification
      is less subjective and emotional than "very good", "good", "fair" and
      "poor".(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536038
TI  - Arthroscopic partial meniscectomy: 5-year follow-up.
AB  - The purpose of this study was to determine the influence of preexisting
      chondromalacia at time of surgery on the results at a minimum of 5 years follow
      up of arthroscopic partial meniscectomy. The patients were divided into two
      groups: group I (87 patients, average age 29.8 years) with no intraoperative
      findings of chondromalacia at the time of surgery, and group II (234 patients,
      average age 39.2 years) with chondromalacia at the time of surgery. The follow-up
      period was 70-86 months, with the criterion of a minimum of 5 years in each
      patient. Postoperative changes were evaluated according to Fairbank's
      classification and preoperative X-rays were compared to follow-up X-rays. For
      statistical analysis the Mann-Whitney test was used. In both groups arthroscopic
      partial lateral meniscectomy led to worse results in respect of the development
      of osteoarthritis. Following partial medial meniscectomy preexisting
      chondromalacia had a negative influence on the radiological outcome. An increase
      of osteoarthritis was also proven in our patient population which was
      statistically significantly related to age and female sex (P = 0.002).

PMID- 8536039
TI  - Tibial plateau fractures: the arthroscopic option.
AB  - Tibial plateau fractures remain one of the most difficult fractures to treat. A
      multitude of classifications exist and several treatment options have been
      advocated. In the last few years arthroscopy has been used in the treatment of
      these fractures. We report our experience of treating over 30 cases by this
      method and review the literature.

PMID- 8536040
TI  - Review on tension in the natural and reconstructed anterior cruciate ligament.
AB  - This article reviews the methodology and results of published studies concerned
      with tension in the natural and reconstructed anterior cruciate ligament (ACL).
      This also includes studies of fiber length changes with knee motion and the
      relationships between graft tunnel placements and isometricity. Little work has
      been done in vivo: in humans, length changes of the anterior ACL fibers have been
      measured at operation, while animal longitudinal studies have been few and have
      given conflicting results. Work in vitro has used many methods to study ACL
      tension directly or indirectly, via length changes in fibers, but many authors
      have reported variable results, caused partly by inter-specimen differences and
      lack of control of forces or kinematics. It seems likely that different grafts
      require different peroperative tensions to restore normal stability when measured
      immediately after application at one knee position. But graft placement and the
      angle at which tensioning is performed also matter. Over-tensioning constrains
      knees under load cycling. Similarly, it is difficult to measure and therefore
      also to decide how tension should be distributed between an ACL graft and and
      augmentation to the graft. It was concluded that the published studies provide
      many guidelines for the effects of different graft placements or tensioning
      protocols but, overall, there is little firm evidence on which to recommend any
      particular ACL reconstruction protocol.

PMID- 8536041
TI  - Anterior cruciate and medial collateral ligament injury. ACL reconstruction and
      functional treatment of the MCL.
AB  - Since August 1989 we have treated acute anteromedial instabilities with medial
      instability of 1+ and 2+ by augmented anterior cruciate ligament (ACL)
      reconstruction alone. Subsequently, functional therapy for the lesion of the
      medial collateral ligament (MCL) was carried out. In a follow-up examination, we
      evaluated Lysholm, Marshall, OAK and IKDC scores, measured stability with the KT
      1000, and tested isokinetic muscle function in 28 patients. The majority
      demonstrated stable healing of the MCL and ACL and good or excellent knee
      functions and muscle strength.

PMID- 8536042
TI  - Roentgenographic and magnetic resonance imaging of anterior cruciate
      reconstruction using a patellar tendon graft--correlations with physical
      findings.
AB  - The purpose of this study was to evaluate the influence of the graft positioning
      on the clinical outcome and magnetic resonance imaging (MRI) signal of the graft
      following anterior cruciate ligament (ACL) reconstruction using the central one
      third of the patellar tendon. Twenty-two patients with a chronic anterior
      instability underwent a modified Marshall-MacIntosh procedure, while 27 with a
      subacute torn ACL had an ACL reconstruction using a free bone-patellar tendon
      bone graft. The patients were retrospectively reviewed with a 1.8-year average
      follow-up (1-3 years). The clinical result was evaluated through the comparative
      range of motion and the residual laxity as measured with the KT 1,000
      arthrometer. The roentgenographic analysis was performed from anteroposterior
      (AP) and mediolateral (ML) views, made first on one-leg standing with the knee at
      30 degrees of flexion, and secondly at "zero" extension with active quadriceps
      contraction. Lines were drawn to visualise the location of the tibial and femoral
      tunnels in relation to the tibial plateaus and the intercondylar roof represented
      by Blumensaat's line. The analysis of the lateral MRI views of the graft allowed
      discrimination between homogenous and heterogenous graft signals. On lateral
      roentgenograms of normal knees, it was found that Blumensaat's line crossed the
      surface of the medial tibial plateau at 30% +/- 9% of its sagittal width (20%-40%
      range), demonstrating the variability of intercondylar roof inclination. The
      range of motion was normal in 34 patients (group I), 9 patients had a flexion
      deficit (group II), and 6 exhibited an extension deficit (group III). The
      residual laxity was similar in each group (P > 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8536043
TI  - Experience with the Leeds-Keio artificial ligament for anterior cruciate ligament
      reconstruction.
AB  - Artificial anterior ligament reconstruction was very popular between 1975 and
      1990. Recently, disappointing results have been published. We reviewed 68
      patients who had received an artificial anterior cruciate ligament reconstruction
      1 year and 5 years after their operation. The Leeds-Keio device was used as a
      scaffold. The ligament failed in 32 knees. This was arthroscopically confirmed in
      20 cases. The other 12 knees were grossly unstable, with a reappearance of pivot
      shift, anterior drawer sign and high KT 1000. Generally, we found a marked
      increase in laxity over the period of investigation. Several biopsies were taken
      during arthroscopic examination of suspected ruptures. They showed lack of
      collagenisation and ingrowth.

PMID- 8536044
TI  - Donor-site morbidity after harvest of a bone-tendon-bone patellar tendon
      autograft.
AB  - The effects of closure of the peritendineum and bone grafting of the patellar
      defect after harvest of the bone-tendon-bone patellar tendon autograft was
      investigated prospectively in two groups of 25 patients. Anterior cruciate
      ligament (ACL) reconstruction was performed with minimally invasive techniques
      either arthroscopically or via mini-arthrotomy. Patellar height, size of bony and
      tendon defects, and overall result were followed up for 2 years postoperatively.
      The results showed that closure of the peritendineum enhances healing of the
      patellar tendon defect and restores a normal appearance of the tendon within 2
      years. We have stopped bone grafting the patellar defect with cancellous bone
      because of the risk of formation of painful spurs at the inferior pole of the
      patella which occurred in 36% of patients.

PMID- 8536045
TI  - Mechanisms of anterior cruciate ligament ruptures in skiing.
AB  - In the years 1980-1989, 78 patients with an acute anterior cruciate ligament
      (ACL) rupture sustained during downhill or cross-country skiing were treated at
      the University Hospital of Tampere, Finland. In every case, the ACL rupture was
      verified at arthroscopy or open surgery. The injury mechanism could be clarified
      for 51 patients using a collection of pictures of the most typical injury
      mechanisms in skiing. Thirty-nine of them (76%) were women and 12 men (24%). In
      32 cases (63%) the injury occurred during downhill skiing and in 19 cases (37%)
      during cross-country skiing. In 24 cases (47%) the injury mechanism was valgus
      external rotation, in 21 cases (41%) flexion-internal rotation, in two cases
      hyperextension-internal rotation, while in four cases the exact mechanism
      remained unclear. The great majority of the patients with an injury mechanism of
      flexion-internal rotation were women (90%), and they were significantly older
      than the patients with an injury mechanism of valgus-external rotation (mean ages
      44 and 34 years, respectively; P < 0.05). According to the patients' subjective
      evaluation, the main reasons for the injury were poor ski area conditions (such
      as slippery slopes and trails) and deficient equipment, especially poorly
      functioning bindings. Many of them had had little skiing experience before the
      accident.

PMID- 8536046
TI  - Biochemical properties of collagen from ligaments and periarticular tendons of
      the human knee.
AB  - The biochemical properties of collagens from the periarticular connective tissues
      of the human knee (ligaments, semitendinosus and gracilis tendons, and the
      iliotibial band) were investigated in subjects ranging from 20 to 70 years of
      age. Although the total collagen content of most tissues was more than 90% of the
      dry weight, the anterior cruciate ligament and the iliotibial band had relatively
      low collagen contents. There were no significant changes in the tissue collagen
      content with aging. However, the anterior cruciate ligament and the patellar
      tendon of the 20-year-old subject had a higher content of soluble collagen than
      the other ligaments and tendons. The iliotibial band of the 20-year-old subject
      contained more collagen that was soluble by a combination of salt, sodium citrate
      extractions and pepsin digestion. Dihydroxylysinonorleucine was the major
      reducible cross-link of collagen from all the ligaments. The amount of
      dihydroxylysinonorleucine in the anterior cruciate ligament of the 20-year-old
      subject was much higher than that in the other ligaments. In contrast, the
      tendons and the iliotibial band contained a large amount of histidino
      hydroxymerodesmosine and hydroxylysinonorleucine, while the patellar tendon was
      the only tendon with a significant content of dihydroxylysinonorleucine.
      Hydroxypyridinium non-reducible cross-links were more abundant in collagens from
      ligaments than in collagens from the other tissues. The cross-link study and the
      analysis of collagen solubility showed that patellar tendon collagen more closely
      resembled the collagen from the anterior cruciate ligament than that from
      periarticular tendons. It was also shown that the anterior cruciate ligament
      contains relatively immature collagen compared with the other ligaments.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8536047
TI  - Anatomical and biomechanical characteristics of human meniscofemoral ligaments.
AB  - The meniscofemoral ligaments (MFL) of 26 human cadaver knees were studied to
      determine their structural importance. The incidence of at least one MFL in each
      of the specimens studied was 100%, and 46% of the specimens had both MFL
      ligaments (Humphry and Wrisberg). Another 23% had a single Humphry ligament, and
      the remaining 31% had a single Wrisberg ligament. A laser micrometer system was
      used to measure cross-sectional shape and area. The average cross-sectional areas
      of the Humphry and Wrisberg ligaments were 7.8 +/- 4.7 mm2 and 6.7 +/- 4.1 mm2,
      respectively. In specimens with both a Humphry and Wrisberg ligament, the larger
      ligament area was on average 100% greater than the smaller ligament area. The
      average ratios of the cross sectional areas of Wrisberg and Humphry to that for
      the PCL within the same knee were 12.0% +/- 7.7% and 11.9% +/- 5.7%,
      respectively. The structural properties of the MFL bone-ligament-meniscus complex
      and the mechanical properties of the MFL midsubstance were determined by uniaxial
      tensile testing. The average stiffness, ultimate load, and energy absorbed at
      failure were, respectively, 49.0 +/- 18.4 N/mm, 297.4 +/- 141.4 N and 1125.4 +/-
      735.8 N/mm. The tangent modulus between 4% and 7% strain was 355.1 +/- 234.0 MPa.
      Our findings suggest that the MFL is a significant biomechanical structure in the
      knee because of its size, stiffness, and strength.

PMID- 8536048
TI  - A new surgical procedure for the treatment of patella infera.
AB  - A new method for the treatment of patella infera is presented. This technique is
      based on the previously described procedure for treatment of old ruptures of the
      patellar ligament. The main advantage of this technique is the achievement of a
      normal patellar position without the adverse effects on the knee extensor
      mechanism found with other techniques, such as patellectomy or elevation of the
      tibial tubercle. The main surgical steps of this technique are outlined and the
      preliminary results reported.

PMID- 8536049
TI  - Osteochondritis dissecans of the patellofemoral groove in athletes: unusual cases
      of patellofemoral pain.
AB  - Five athletes who developed osteochondritis dissecans in the patellofemoral
      groove in the course of sports events at high school and college league level are
      described. They were male athletes complaining of anterior knee pain. When
      examining young people engaged in violent sports, it is well to remember that
      they might have osteochondritis dissecans in the patellofemoral groove.
      Clinically, four of the five patients under discussion were characterized by
      tight movements of the patella in a direction parallel to its transversal axis. X
      ray studies in lateral projections and CT scans provided useful tools for
      definitive diagnosis, but AP radiography was no help in diagnosis. Release of a
      tight lateral retinaculum with or without drilling on the degenerated cartilage
      was effective in the treatment of osteochondritis dissecans of the patellofemoral
      groove in three of the four patients.

PMID- 8536050
TI  - Prevention of injuries in long-distance runners.
AB  - The possibility of reducing the incidence of injuries in long-distance runners
      was investigated in 41 recreational long-distance runners. They were divided into
      two matched groups according to age, sex, weight, height, experience, training
      and incidence of injury during the previous year. The runners in the study group
      were clinically investigated before the season started, and individual training
      programmes were drawn up. The other group served as controls. The runners
      receiving prevention and training programmes improved in training technique and
      had increased training mileage, race participation and racing mileage. In 1 year
      a total of 50 injuries were recorded, 29 in the study group and 21 in the
      controls. The injury incidence per 1000 hours of competition was significantly
      lower in the study group with a preventive training regimen than in the controls
      (30.7 versus 62.5).

PMID- 8536051
TI  - Late follow-up results of operative ankle arthroscopy in patients under local
      anaesthesia.
AB  - The purpose of this study was to evaluate our long-term results of operative
      ankle arthroscopy in local anaesthesia, without tourniquet and antibiotic
      prophylaxis, and to see whether we could produce the same results other
      investigators had published using general anaesthesia. Between 1987 and 1992, 51
      operative ankle arthroscopies were performed--all as out-patient procedures.
      Thirty-six patients had local anaesthesia, 7 had general anaesthesia, one had
      spinal anaesthesia and one had epidural anaesthesia. No prophylactic antibiotics
      were given. Indications for surgery were the same for patients who had local
      anaesthesia as for those who had the other types of anaesthesia. Nineteen
      patients had partial synovectomies, 8 had removals of osteophytes, 7 had
      debridements of osteochondral fractures, 6 had debridements of mild degenerative
      osteoarthritis, 3 had loose bodies and 2 had septic arthritis. After a mean of 3
      years (range 1-8) the patients were sent a questionnaire. They were asked to rate
      activity level, pain, swelling, and limb stiffness on a four-grade scale pre- and
      postoperatively and to rate their total subjective improvement. They were also
      asked if they would undergo the same procedure again knowing the outcome of the
      procedure. Forty-five patients (88%) were available for follow-up. Thirty-four
      patients (76%) were improved, 10 remained unchanged, and one became worse after
      surgery. No correlation existed between preoperative symptom duration, sex,
      trauma, type of anaesthesia, postoperative diagnosis or type of surgical
      procedure. Minor complications occurred in 11% of patients. Eighty-four percent
      of the patients said they would undergo the same procedure again. The type of
      anaesthesia used did not influence this decision.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8536052
TI  - Arthroscopic surgery of the hip: current status.
AB  - Arthroscopy of the hip is now recognised as a valuable diagnostic and therapeutic
      procedure [23]. It is still relatively new and remains largely in the hands of a
      few specialist centres, but orthopaedic surgeons are increasingly willing to
      provide it as part of their own service. This article outlines its background and
      details its clinical and technical application.

PMID- 8536053
TI  - Problems in regaining full extension of the knee after anterior cruciate ligament
      reconstruction.

PMID- 8536054
TI  - Molecular analysis of mutations in thyroid tumors with TGGE.
AB  - Immunohistochemical demonstration of overexpression of the p53 protein indicates
      a mutational alteration of the gene. Our own investigations of 59 differentiated
      thyroid carcinomas revealed an overexpression in 15% of the tumors. A correlation
      to unfavourable tumor prognosis was found (stage I and II: 0/11 (0%); stage III:
      4/26 (14%); stage IV: 5/22 (23%)). For screening of one out of more than 300
      possible mutations temperature gradient gel electrophoresis was employed.
      Analysis of the highly-conserved regions of the p53 gene (exon 5 to 8) could
      demonstrate a mutation in only 1 out of 31 differentiated thyroid carcinomas. The
      question arises whether accumulation of the protein is due to a mutational event
      or rather other molecular mechanisms.

PMID- 8536055
TI  - Calmodulin antagonist W7 increases inositol phosphates in insulin secreting
      RINm5F cells.
AB  - W7, a calmodulin antagonist, has been reported to increase cytosolic free calcium
      concentration [Ca2+]i in non stimulated rat insulinoma cells (RINm5F). And this
      effect was not due to enhanced calcium uptake. In the present study the effect of
      calmodulin antagonist W7 on the inositol phosphate turnover of RINm5F cells was
      studied. Inositol phosphates were separated using a new modified technique of
      anion-exchange high performance liquid chromatography (HPLC). It was observed
      that W7 significantly increased inositol trisphosphate and inositol bisphosphate
      within 5 and 15 sec, respectively. No changes of inositol phosphates were
      detected employing W5, a chlorine-deficient analogue of W7 without calmodulin
      antagonistic action. Our data are in favour of the view that (I) calmodulin may
      be involved in inositol phosphate metabolism of RINm5F cells and that (II) the
      increase of [Ca2+]i in response to W7 as reported previously may be due to
      elevation of inositol trisphosphate.

PMID- 8536056
TI  - Regulation of growth hormone (GH), insulin-like growth factor (IGF)I, IGF binding
      proteins -1, -2, -3 and GH binding protein during progression of liver cirrhosis.
AB  - The aim of this study was to investigate the regulation of various proteins of
      the GHIGF axis during progression of liver failure and to search for potential
      prognostic markers of functional hepatic reserve. Serum levels of growth hormone
      (GH) and high affinity growth hormone binding protein (GHBP), insulin-like growth
      factor I (IGF-I) and IGF binding proteins (IGFBP) -1, -2 and -3 were determined
      in patients with liver cirrhosis. A continuous decline in the concentrations of
      IGF-I, IGFBP-3 and serum GH-binding activity (GHBP) was observed during
      progression of cirrhosis and the data correlated significantly with choline
      esterase, total serum protein and the Child score. In addition, GHBP showed a
      significant correlation with the enzymatic activity of glutamate dehydrogenase or
      transaminases and seems so to be influenced by the degree of liver cell damage.
      In contrast, IGFBP-1 and IGFBP-2 levels were significantly elevated in
      preterminal disease suggesting an upregulatory mechanism is still effective in
      this situation. Only when liver function had markedly deteriorated, the serum
      levels of these two parameters decreased again, possibly due to an impaired
      synthesis. The excellent correlation between the serum levels of IGF-I (r = 
      0.64, p < 0.001) or IGFBP-3 (r = -0.67, p < 0.001) and the Child score index
      suggests that they reflect the hepatic functions just as conventional indicators.
      For an appropriate interpretation of the liver function the measurement of the
      growth related peptides can be a valuable tool to estimate pathological
      alteration in the functional hepatic reserve or in the glucose homeostasis.

PMID- 8536057
TI  - Atrial natriuretic peptide (ANP) in preeclampsia-like syndrome in a rat model.
AB  - The pathophysiology of preeclampsia has not been fully clarified. A variety of
      factors have been implicated with this disease including vasoactive peptides and
      hormones during the last 20 years. Inadequate generation of atrial natriuretic
      peptide (ANP) has been one of the mechanisms discussed as to possibly contribute
      to the development of hypertension. In human pregnancy multiple studies of ANP
      plasma-concentration in normal or hypertensive pregnancies showed conflicting
      results. The complexity of the clinical findings of hypertension in pregnancy
      makes it very difficult to carry out comparative clinical and biochemical studies
      in humans. In an animal experience genetic as environmental influences could be
      excluded. Therefore, the present study shows an experimental preeclampsia-like
      syndrome in the rat by reduction of the utero-placental flow. We observed a
      significant increase of plasma ANP in pregnant rats with experimentally induced
      hypertension. Furthermore, our results suggest that the ventricles could be an
      important source of ANP gene expression.

PMID- 8536058
TI  - Effect of retinoic acid on the proliferation and alkaline phosphatase activity of
      osteoblastic MC3T3-E1 cells by modulating the release of local regulators from
      monocytes.
AB  - There has been some evidence suggesting an important role of mononuclear cells at
      bone remodeling sites in the coupling of bone formation to bone resorption. Since
      cells of the monocyte-macrophage lineage produce important local regulators of
      bone remodeling, we examined effects of human monocytes-conditioned medium (CM)
      treated with retinoic acid on [3H] thymidine incorporation (TdR) and alkaline
      phosphatase (ALP) activity of osteoblastic MC3T3-E1 cells. Treatment of MC3T3-E1
      cells with retinoic acid (10(-8) to 10(-6) M) caused an inhibition of TdR in a
      dose-dependent manner and an inhibition of ALP activity at 10(-6) M. Conditioned
      medium from monocytes untreated with retinoic acid caused a stimulation of TdR
      and an inhibition of ALP activity in these cells. In contrast, treatment of
      monocytes with retinoic acid (10(-8) or 10(-6) M) abolished both stimulation of
      DNA synthesis and inhibition of ALP activity induced by CM. The present study
      suggested that retinoic acid modulated osteoblast proliferation and ALP activity
      not only directly but also indirectly, presumably through modulating the release
      of local regulators as to bone remodeling from monocytes.

PMID- 8536059
TI  - Increased production of erythropoietin after application of antidiuretic hormone.
      A consequence of renal vasoconstriction?
AB  - The renal glycoprotein hormone erythropoietin (Epo) is the key element in the
      feedback control of the production of red blood cells (RBC) in bone marrow.
      Excess of antidiuretic hormone (ADH) increases the RBC mass by increasing the
      synthesis of Epo. The mechanism of the Epo stimulating effect of ADH is not fully
      understood. Rats were treated with ADH with or without prior injection of a V1a
      receptor antagonist. Additional experiments were carried out by stimulating the
      V2-receptor by desmopressin (DDAVP). Epo level in plasma was doubled following
      injections of ADH. Blockade of the V1a-receptor completely abolished the Epo
      stimulating effect of ADH. Neither ADH alone nor the combined giving of V1a
      antagonist and ADH had an influence on the glomerular filtration rate or the
      renal plasma flow. Therefore, the increased Epo synthesis after application of
      ADH cannot be explained by a constriction of renal blood vessels with consecutive
      ischemic hypoxia. There is rather a direct stimulation of Epo synthesis by ADH
      via its receptors. Since a selective stimulation of the V2-receptor by DDAVP did
      not increase to Epo level in plasma, the observed increase of Epo is mediated by
      the V1a-receptor.

PMID- 8536060
TI  - Efficiency of various dissociation methods for the preparation of thyroid single
      cell suspensions.
AB  - For comparison of the physiological potential of single thyroid cells versus
      cells integrated into follicles it would be ideal to work with suspensions
      consisting exclusively of single cells instead of a mixture of single cells and
      follicle fragments. In this study, various techniques for the isolation of single
      cells have been tested for their effect on cell viability, the ultrastructure of
      the isolated cells, the percentage of single cells and the ability of these cells
      to form follicles in culture. In addition, the cells were characterized for the
      preservation of their morphology and the ability to respond to TSH by comparing
      their immunocytochemical staining pattern with anti-vimentin and anti-ras p21
      antibody to that of the intact thyroid tissue. Dispase treatment of thyroid
      tissues alone produced suspensions with a relatively small proportion of single
      cells. These cells stained with anti-vimentin and anti-ras p21 antibody to a
      similar percentage as thyroid cells in the intact gland. A combination of dispase
      treatment with either filtration or trypsin treatment severely compromised the
      viability of the cells. A high proportion of single cells with a good viability
      could be obtained either by centrifugation of dispase treated tissues or by
      culturing of dispase treated tissues as monolayers and subsequent detachment from
      the culture vessels with trypsin. Whereas the immunological staining with anti
      vimentin and anti-ras oncogene antibody in the centrifuged cells resembled that
      of intact tissue, cells cultured as monolayers reacted differently. The
      differences in the immunological staining were still observed when the cells
      which had been grown as monolayers were stimulated with TSH. Differential
      centrifugation appeared to be the ideal method for the isolation of unaltered and
      viable single cells but is a rather laborious method to obtain larger amounts of
      single thyroid cells.

PMID- 8536061
TI  - The inhibitory effect of beta-endorphin on LH release in ovariectomized rats does
      not involve the preoptic GABAergic system.
AB  - In rats, beta-endorphin (beta-END) and gamma-aminobutyric acid (GABA) suppress LH
      secretion by hypothalamic mechanisms involving the preoptic area (POA). Systemic
      injection of naloxone (NAL) increases LH secretion in male rats, an effect which
      can be prevented by coadministration of GABA agonists. Application of NAL into
      the POA of ovariectomized (ovx), progesterone substituted sheep modulates
      preoptic GABA release. These findings have been interpreted such that the
      endogenous opioids act via the preoptic GABAergic system to regulate LH release.
      To evaluate this hypothesis we implanted ovx rats with push pull cannula into the
      POA and measured GABA secretion prior to and during the preoptic application of
      either NAL or beta-END. Blood samples were collected to assess the effects of the
      drugs on LH secretion. In addition, ovx rats were substituted with estradiol (E2)
      to induce a negative feedback effect on LH release. Intrapreoptic application of
      beta-END caused a rapid decline of LH release in ovx rats which was completely
      reversible after termination of beta-END perfusion. Though LH levels were clearly
      suppressed, no change of GABA release in the POA was observed. During preoptic
      NAL perfusion both LH secretion and GABA release remained unaffected. Likewise,
      during beta-END perfusion into the POA of E2 treated rats neither LH nor GABA
      secretion changed. In contrast, NAL perfusion rapidly increased LH release but
      again this action of the opioidergic drug was not accompanied by alterations of
      GABA release. We conclude from these data: 1) Intrapreoptically applied beta-END
      inhibits LH release only in the absence of steroids. In turn, blockade of opioid
      receptors is effective only in the presence of steroids. Both findings indicate
      that in the POA opioidergic activity is low in ovx rats, but high during negative
      feedback of E2. 2) No changes of GABA secretion were observed during
      manipulations of the opioidergic tonus in the POA suggesting that both beta-END
      and GABA do not interact to regulate LH release. Thus, beta-END may directly
      inhibit the activity of GnRH neurons located in the POA or acts via a
      neurotransmitter other than GABA.

PMID- 8536062
TI  - Immunoreactive human chorionic gonadotropin beta core fragment in human
      pituitary.
AB  - The human pituitary has been shown to produce small amounts of immunoreactive
      human chorionic gonadotropin (hCG) and its alpha- and beta- subunit (hCG alpha,
      hCG beta). The aim of the present studies was to further examine the various hCG
      related materials in the human pituitary, particularly to search for the
      existence of pituitary hCG beta core fragment (hCG beta cf)--like material. HCG
      beta cf has been found in the urine of pregnant women, patients with
      trophoblastic tumors and also in postmenopausal women. Gel chromatography of
      pituitary extract on Superdex 200 showed three distinct peaks of hCG-related
      immunoreactivities, i.e. hCG, hCG beta and hCG beta cf, which were
      distinguishable from hLH and hLH beta peaks. HCG beta cf was recognized by a
      specific immunometric assay (crossreactivities with hCG beta 0.016%, hLH beta
      0.04%), but unreactive in an hLH + hLH beta assay. It was purified and displayed
      physical properties similar to those of hCG beta cf derived from pregnancy urine.
      Apart from immunological differences between the small molecular weight forms or
      fragments of hCG and LH origin, reversed phase HPLC was able to physically
      discriminate between hCG beta cf and hLH beta fragment. The latter was much more
      abundant than the former in the pituitary extract. HCG beta cf showed
      microheterogeneity related to its sialic acid content. In conclusion, the present
      data indicate that immunoreactive hCG beta cf is present in human pituitary
      extracts. The physical and immunological properties of pituitary hCG beta cf are
      distinguishable from those of the more abundant hLH beta and its fragment, and
      compare favorably with those of urinary hCG beta cf of trophoblastic origin.

PMID- 8536063
TI  - Differences in expression of angiotensin II receptors and renin in porcine and
      bovine ovaries.
AB  - The expression of angiotensin (Ang) II receptors, active renin and prorenin in
      porcine and bovine ovarian follicles and corpora lutea was investigated and
      compared. In the wall tissue of porcine follicles, the Ang II receptor density
      was 47 (range 19-97; n = 13) fmol/mg membrane protein. The active renin
      concentration was 1.32 (0.40-3.43; n = 23) GU/kg wet tissue. These values were
      about 35-fold and 15-fold lower, respectively, than previously found in bovine
      follicles. No prorenin could be detected in the porcine follicular wall tissue.
      Ang II receptors of subtype 2 (AT2 receptors) with a dissociation constant (Kd)
      of 1.01 (0.64-1.79; n = 8) nmol/l for [Sar1-Ile5-Ile8]-Ang II were demonstrated
      in the bovine corpus luteum. The receptor density was 22.7 (1.9-93; n = 26)
      fmol/mg membrane protein, which was about 10-fold higher than in porcine corpora
      lutea. The active renin concentration was 20.7 (2.2-60.0; n = 26) GU/kg tissue in
      bovine and 0.40 (0.16-1.09; n = 17) GU/kg tissue in porcine corpora lutea. No
      prorenin could be detected in corpora lutea from both species. The variation
      between species in expression of the ovarian renin-angiotensin system indicates
      the existence of species differences in the physiological role.

PMID- 8536066
TI  - Current problems in the management of ROP.
AB  - Guidelines for screening for retinopathy of prematurity (ROP) and indications for
      treatment are well established, but implementation of screening and delivery of
      treatment may be problematical. We have performed a national survey of 118
      specialised units dealing with at risk neonates to audit current practice in
      Britain and to identify practical problems with screening and with treatment. A
      screening policy for neonates at risk is in practice at 97% of units, performed
      by consultant ophthalmologists in 86% of centres. Units referred to specialised
      treatment centres in 23% of cases. An average of 54 infants at risk of ROP were
      screened by each of 118 units throughout Britain in 1993, and approximately 3% of
      these infants underwent treatment for ROP. Cryotherapy was used for treatment in
      85% of units, laser photocoagulation in 51% and both treatment modalities were
      used in 36% of units. Less than 1/4 of the neonatologists polled were of the
      opinion that they should be trained to screen for ROP themselves. These results
      show that the screening guidelines have been successfully implemented in Britain,
      but demonstrate a wide variation in practice. Problems with screening and
      treatment are discussed.

PMID- 8536064
TI  - Age modulates effects of thyroid dysfunction on sex hormone binding globulin
      (SHBG) levels.
AB  - Symptoms of thyroid dysfunction are difficult to detect in elderly people and TSH
      is sometimes unreliable. We therefore tested the value of SHBG as a marker of
      thyroid hormone action on the liver to determine the thyroid status of elderly
      people. Aging euthyroid men and women have a significant increase in SHBG (p >
      0.0001). In aging women the decrease in SHBG with hypothyroidism and increase
      with hyperthyroidism are highly significant (p < 0.0001 and p < 0.0005
      respectively). No significant variation in SHBG was observed in men with thyroid
      dysfunction. SHBG can help to determine the thyroid status of aging women.

PMID- 8536070
TI  - Coexpression of the gastrin and somatostatin genes in differentiating and
      neoplastic human cells.
AB  - Double immunofluorescence and in situ hybridizations performed on adjacent thin
      sections show that a population of normal antropyloric cells of the human stomach
      expresses both gastrin and somatostatin mRNA's and the corresponding peptides.
      Such cells were present in both adult and fetal antropyloric mucosa and were
      situated in the regenerative (isthmus) region of the antropyloric tubes. It is,
      hence, likely that these cells represent immature endocrine cells that yet have
      to be committed to either the gastrin or somatostatin lineage. Cells coexpressing
      gastrin and somatostatin were also detected in pancreatic endocrine tumours. The
      presence of gastrin-somatostatin cells during development and in tumours suggests
      that gastrin and somatostatin cells may differentiate from such multipotent
      precursor cells.

PMID- 8536071
TI  - Argyrophilic nucleolar organizer regions. A revised version of the Ag-NOR
      staining technique.
AB  - Silver staining techniques developed to demonstrate argyrophilic nucleolar
      organizer regions (Ag-NORs) have been widely applied in a variety of cell kinetic
      studies, using the mean number of AgNORs in tumour cells as a marker for
      malignancy of certain types of neoplasms. However, the AgNOR techniques currently
      available are not entirely satisfactory, as unspecific silver precipitates
      readily form in the sections. On the other hand, the contrast staining may be so
      weak as to render identification of the AgNORs difficult. In the present study,
      some of the key factors influencing the outcome of AgNOR staining were evaluated
      in a more systematic way. A modified AgNOR staining procedure is now proposed,
      giving highly contrasting AgNORs with minimal unspecific silver precipitation,
      thus facilitating both manual and computerized counting. The new technique
      involves the use of microwave irradiation in order to shorten the processing
      time, the use of gelatin as a protective colloid, and a Farmer's solution to
      optimize the specificity of the technique.

PMID- 8536072
TI  - DNA localization in nuclear fragments of apoptotic ameloblasts using anti-DNA
      immunoelectron microscopy: programmed cell death of ameloblasts.
AB  - Ameloblasts responsible for tooth enamel formation are classified into two
      different phases: secretion and maturation. At the transition between these
      secretion and maturation stages, a considerable number of cells die. In this
      study, we examined the morphology of degenerating ameloblasts by conventional
      electron microscopy, and DNA cleavage in degenerating ameloblast nuclei by the in
      situ terminal transferase assay. The results suggest that apoptosis (programmed
      cell death) in ameloblasts, including DNA ligation is induced at the transitional
      stage. The nuclear fragments, chromatin condensation and DNA relocation in
      apoptotic nuclei were examined quantitatively by post-embedding anti-DNA
      immunogold electron microscopy and the in situ terminal transferase assay
      combined with electron microscopy. Numerical analysis revealed that immunogold
      labeling density in the condensed chromatin of apoptotic nuclei was comparable on
      the average to that in the perinuclear heterochromatin of normal nuclei, and that
      individual apoptotic nuclear fragments exhibited highly variable to that of
      normal heterochromatin, to fragments with densities twice as high as that of
      normal heterochromatin. The in situ terminal transferase assay combined with
      electron microscopy detected DNA ends exposed by ultrathin sectioning as well as
      DNA cleavage by a putative endonuclease. In conclusion, the state of the DNA,
      including its ligation and degeneration, changes gradually during chromatin
      condensation and nuclear fragmentation of apoptosis.

PMID- 8536073
TI  - Lectin binding defines and differentiates M-cells in mouse small intestine and
      caecum.
AB  - M-cell surface glycoconjugate expression was investigated by applying a panel of
      lectins to whole fixed mouse Peyer's and caecal patches. While the majority of
      lectins failed to identify mouse M-cells, the lectin Euonymus europaeus
      differentially stained the surface of M-cells in both mouse Peyer's and caecal
      patches, and the lectins Ulex europaeus II and Bandeiraea simplicifolia I
      isolectin B4 identified M-cells in the Peyer's and caecal patch follicle
      associated epithelium, respectively. These three mouse M-cell markers failed to
      identify rat and rabbit Peyer's patch M-cells, although both Euonymus europaeus
      and Ulex europaeus II differentially stained M-cells in the periphery of rabbit
      caecal patch domes. These site and species related variations in M-cell surface
      glycoconjugate expression may reflect the local microorganism populations and
      will have important implications if orally delivered vaccines and drugs are to be
      targeted to M-cells via their surface glycoconjugates.

PMID- 8536074
TI  - Calbindin-D9k expression in the pregnant cow uterus and placenta.
AB  - Calbindin-D9k (CaBP9k) is a vitamin D-dependent, calcium binding protein first
      identified in the cytoplasm of the intestinal epithelial cell. Using biotin
      streptavidin immunohistochemistry, CaBP9k was localized to the maternal
      caruncular epithelium, fetal chorionic epithelium, and trophoblastic binucleated
      cells of the bovine placenta. Within the maternal epithelium the intensity of
      staining increases from second trimester pregnancies to term pregnancies,
      indicating a higher intracellular concentration of CaBP9k in the epithelium at
      term. Luminal and glandular epithelium of the non-caruncular endometrium also
      stained positively for CaBP9k in all stages of pregnancy observed. No CaBP9k was
      identified within the stroma or myometrium of the pregnant cow uterus. The
      increased level of CaBP9k in the caruncular epithelium during the last trimester
      is hypothesized to be in response to the rising demand for calcium to aid in the
      mineralization of the fetal skeleton. CaBP9k may play a role in enhancing calcium
      transport across the placenta in cattle.

PMID- 8536075
TI  - Dynamic reorganization of the alkaline phosphatase-containing compartment during
      chemotactic peptide stimulation of human neutrophils imaged by backscattered
      electrons.
AB  - Scanning electron microscopy (EM) and cytochemical techniques were used to
      examine the alkaline phosphatase-containing compartment in human neutrophils
      after stimulation with nanomolar concentrations of N-formylmethionyl-leucyl
      phenylalanine (10(-8) M fMLP). Alkaline phosphatase (AlkPase) activity was
      demonstrated with a lead-based metal capture cytochemical method. The reaction
      product was visualized with the backscattered electron imaging mode of scanning
      EM, and analyzed by electron probe X-ray microanalysis. Alkaline phosphatase
      activity was detected only in fMLP-stimulated neutrophils; unstimulated
      neutrophils displayed no activity. Stimulation of human neutrophils with 10(-8) M
      fMLP induced a time-dependent intracellular redistribution of irregular round or
      tubular granules containing alkaline phosphatase activity, as seen by
      backscattering. The intracellular redistribution of alkaline phosphatase activity
      was accompanied by increased cytochemical activity on the cell surface. The
      reaction product was localized preferentially on ridges and folds of polar
      neutrophils. Reorganization of the AlkPase-containing compartment correlated with
      changes induced by fMLP in cell shape, ie, membrane ruffling and front-tail
      polarity, as observed with the secondary electron image mode of scanning EM.
      These findings demonstrate the intracellular reorganization, increase, and
      asymmetric distribution of alkaline phosphatase activity on the plasma membrane
      of human neutrophils after stimulation by chemotactic peptides.

PMID- 8536076
TI  - Robert Feulgen Prize Lecture 1995. New approaches to in situ detection of nucleic
      acids.
AB  - The present paper reviews recent results obtained by different molecular biology
      based, immunocytological approaches to the localization and identification of
      nucleic acids in sections of biological material. Examples of sensitive, high
      resolution detection methods for RNA, DNA or specialized DNA regions are
      presented. Special emphasis is placed on the potential values and limitations of
      these new methods.

PMID- 8536078
TI  - The future of oral health sciences education.

PMID- 8536079
TI  - Initial caries attack and average progression rates in 12-year-old Isle of Wight
      children.
AB  - Initial caries attack and progression rates of posterior approximal carious
      lesions were assessed based on 12-year-old school children residing on the Isle
      of Wight. Bitewing radiographs of a sub-sample of 165 subjects were randomly
      selected from the control group of a dentifrice clinical trial which took place
      between 1984 and 1987. Of the approximal surfaces that were caries-free at the
      first examination 71 per cent of the same surfaces remained caries-free after
      three years, an overall initial caries attack rate averaging 10.7 per cent per
      annum. Of the mesial surfaces of first permanent molars, 455 were initially
      caries-free, 67 per cent of which remained so after a three year period. The
      attack rate of this specified surface was 12.4 per cent per annum. The majority
      of surfaces that were caries-free at the start of the investigation would
      therefore be expected to remain so at least three years later. Caries progression
      appeared to be a slow process with only 12 per cent of initially carious outer
      enamel surface lesions penetrating into dentine after one year. After two years
      this had increased to 46 per cent and after three years, to 62 per cent. For a
      similarly defined group of individuals it would appear likely that the majority
      of early enamel lesions would not reach dentine within two years. For a
      substantial number of subjects this would extend to at least three years.

PMID- 8536080
TI  - Use of the Delphi technique to develop standards for quality assessment in
      diagnostic radiology.
AB  - The Delphi technique is a method for obtaining answers to questions that are
      issues of uncertainty even to experts. The aim of this study was to use the
      Delphi technique to develop two standards for the assessment of the diagnostic
      performance of dentists using radiographs. Two Delphi consensus procedures were
      initiated to determine the presence of visible abnormalities on radiographs and
      their pathological nature. A panel of expert radiologists was independently
      selected. This panel reached consensus on the items of both Delphi procedures
      through a number of rounds of written correspondence. The outcomes of the
      procedures were compared to a histopathologic norm for the presence of pathology.
      The group procedure was described as well as tested for dominance on part of any
      of the individual panellists. It was found that up to 98 per cent agreement
      occurred among the majority of panellists on items of the procedures. The
      panellists were significantly better than dentists in the diagnosis of pathology
      (P < 0.05) and kept improving during the process of consensus formation. In
      neither of the Delphi procedures was the judgement of any panellist dominant (P >
      0.4). It is concluded that, if carefully controlled, the Delphi technique may be
      used in the development of diagnostic standards in oral radiology.

PMID- 8536077
TI  - Robert Feulgen Prize Lecture 1995. Electronic light microscopy: present
      capabilities and future prospects.
AB  - Electronic light microscopy involves the combination of microscopic techniques
      with electronic imaging and digital image processing, resulting in dramatic
      improvements in image quality and ease of quantitative analysis. In this review,
      after a brief definition of digital images and a discussion of the sampling
      requirements for the accurate digital recording of optical images, I discuss the
      three most important imaging modalities in electronic light microscopy--video
      enhanced contrast microscopy, digital fluorescence microscopy and confocal
      scanning microscopy--considering their capabilities, their applications, and
      recent developments that will increase their potential. Video-enhanced contrast
      microscopy permits the clear visualisation and real-time dynamic recording of
      minute objects such as microtubules, vesicles and colloidal gold particles, an
      order of magnitude smaller than the resolution limit of the light microscope. It
      has revolutionised the study of cellular motility, and permits the quantitative
      tracking of organelles and gold-labelled membrane bound proteins. In combination
      with the technique of optical trapping (optical tweezers), it permits exquisitely
      sensitive force and distance measurements to be made on motor proteins. Digital
      fluorescence microscopy enables low-light-level imaging of fluorescently labelled
      specimens. Recent progress has involved improvements in cameras, fluorescent
      probes and fluorescent filter sets, particularly multiple bandpass dichroic
      mirrors, and developments in multiparameter imaging, which is becoming
      particularly important for in situ hybridisation studies and automated image
      cytometry, fluorescence ratio imaging, and time-resolved fluorescence. As
      software improves and small computers become more powerful, computational
      techniques for out-of-focus blur deconvolution and image restoration are becoming
      increasingly important. Confocal microscopy permits convenient, high-resolution,
      non-invasive, blur-free optical sectioning and 3D image acquisition, but suffers
      from a number of limitations. I discuss advances in confocal techniques that
      address the problems of temporal resolution, spherical and chromatic aberration,
      wavelength flexibility and cross-talk between fluorescent channels, and describe
      new optics to enhance axial resolution and the use of two-photon excitation to
      reduce photobleaching. Finally, I consider the desirability of establishing a
      digital image database, the BioImage database, which would permit the archival
      storage of, and public Internet access to, multidimensional image data from all
      forms of biological microscopy. Submission of images to the BioImage database
      would be made in coordination with the scientific publication of research results
      based upon these data.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8536081
TI  - The relationship between caries, fluoridation and material deprivation in five
      year-old children in Country Durham.
AB  - An investigation to assess the impact of fluoridation on the caries experience of
      young children at high and low levels of material deprivation measured by the
      Townsend Index was undertaken in County Durham. Electoral wards were ranked for
      deprivation from 1991 Census data. Dental caries data for 2,751 five-year-old
      children resident in electoral wards in the upper and lower quartiles of material
      deprivation in the County were obtained from a dental survey conducted in 1991
      92. Wards were stratified for fluoridated and non-fluoridated water supply and
      the dental data for the resultant four populations, defined by high and low
      material deprivation and the presence or absence of fluoridation, were analysed.
      The mean dmft values in the four groups were 0.8 in the fluoridated low
      deprivation group, 1.2 in the non-fluoridated low deprivation group, 1.2 in the
      fluoridated high deprivation wards and 2.1 in the non-fluoridated high
      deprivation wards. Thus, with fluoridation the variation in caries between high
      and low deprivation groups was significantly reduced but not eliminated, leaving
      the level significantly lower in the least deprived group, to the continuing
      disadvantage of that deprived group.

PMID- 8536082
TI  - Five-year-old children: changes in their decay experience and dental health
      related behaviours over four years.
AB  - At the time of the 1989-90 survey of 5-year-old children, co-ordinated by the
      British Association for the Study of Community Dentistry, a questionnaire about
      dental health behaviour was sent home to 2,390 parents in Salford and 2,098 in
      Trafford. The response rates were 78 per cent and 81 per cent respectively. The
      questionnaire was repeated for the 5-year-old survey in 1993-94 with the aim of
      finding out if there had been any changes: 2,794 parents were contacted in
      Salford and 2,343 in Trafford. The response rates were 75 per cent and 73 per
      cent. The percentage of children who were having their teeth brushed before they
      were aged one and who had visited a dentist by their second birthday rose in both
      districts. Campaigns at regional and district levels are thought to have
      influenced these improvements. The percentage of children who had experienced
      toothache and the proportion who had received a general anaesthetic for tooth
      extraction were similar in both years.

PMID- 8536083
TI  - The effect of social and personal factors on the utilisation of dental services
      in Glasgow, Scotland.
AB  - This study examined potential mediators of dental attendance among two distinct
      adult populations who lived in contrasting social environments (deprived and
      affluent). The aim of the study was to describe and quantify the effect of both
      the potentially modifiable and the fixed factors which influence use of dental
      services. A two-stage weighted random sampling technique was used to select 863
      participants who were interviewed. Of these participants, 372 lived in 'affluent'
      areas and 491 in 'deprived' areas. The 45 minute interview explored many aspects
      of oral health, and related behaviour and attitudes. The results showed a highly
      significant association between social deprivation and reported dental attendance
      (P < 0.001). Social environment was also significantly related to asymptomatic
      dental attendance. Deprived respondents' dental behaviours were significantly
      affected by life events and yet structural/organisational barriers to attendance
      had a significantly greater impact on the affluent population's dental visiting
      patterns than they did on the deprived population's. A regression model indicated
      that the best predictors of dental attendance were social environment, dental
      anxiety, perceptions about denture wearers and the value placed upon restored
      teeth. The study suggests that the barriers to dental attendance experienced by
      deprived populations are not easily modifiable, but belong instead to a group
      which relate to the socio-political agenda. The study also demonstrates the
      importance of accurate and regularly updated community registers for use in
      population based health services research.

PMID- 8536084
TI  - Periodontal conditions in older age cohorts aged 65 years and older in Japan,
      measured by CPITN and loss of attachment.
AB  - Periodontal conditions were assessed by CPITN and loss of attachment in 601
      elderly people randomly selected in Kitakyushu, Japan. The percentage of
      edentulous persons was 21 per cent, 38 per cent and 65 per cent in the 65-74
      year, 75-84 year and 85 years and older groups, respectively. In dentate persons,
      over 60 per cent had pocket probing depths of 4mm or more; in the majority loss
      of attachment did not exceed 5mm. The mean numbers of sextants with pocket
      probing depths of 4-5mm (CPITN 3) and probing depths of 6mm and more (CPITN 4)
      were similar in each age group. The mean numbers of sextants with both pockets
      and loss of attachment showed no clear difference among groups. Only the mean
      number of excluded (no, or only one tooth) sextants increased with increasing age
      from 1.9 to 3.1. It could therefore be suggested that in the population examined
      the progress of periodontal destruction with increasing age might not be shown by
      an increase in pocket probing depth, loss of attachment or gingival recession,
      but only by an increase in tooth loss. The results for the remaining teeth show
      that a) severe loss of periodontal attachment (6mm or more) was not frequently
      encountered, b) recession (attachment loss without pocketing) was present at only
      very low levels, c) the main periodontal problem seemed to be pocketing, which
      could be treated. It is therefore tempting to suggest that some of the teeth
      already lost, could have been saved if proper self- and professional care had
      been applied.

PMID- 8536085
TI  - Secular changes in treatment in a school dental service.
AB  - The caries decline has affected child dental treatment in many countries. There
      has been a change towards fewer extractions and pulpotomies in deciduous teeth,
      and restorative techniques and restorations in deciduous and permanent teeth have
      become less complex. New materials, particularly glass ionomer cements (GIC),
      have found acceptance. The School Dental Service (SDS) in Western Australia (WA),
      one of the world's largest dental care organisations, holds good data on
      children's dental health and on the types of treatment provided since 1980. This
      paper reports these data. Oral health is recorded as caries experience on a
      random sample of patients. Treatment provided is recorded by operators after each
      patient visit and collated monthly. About 240,000 children (> 90 per cent of
      those eligible) and currently enrolled in the SDS and the clinical staffing is
      about 150-160 dental therapists and 27 dentists. Caries experience has fallen in
      all age groups in recent years, except that in 1992 and 1993 dmft rose slightly
      in six-year-old children. All types of operative treatment are used less
      frequently now than in 1980. In deciduous teeth restorations, GIC dominates but
      amalgam remains the most widely chosen material in permanent teeth. The use of
      fissure sealants (using GIC) peaked in 1988 and, as a result of management
      decisions, has declined since then. The decline in the need for dental treatment
      has reduced costs and enabled the SDS to offer care to an expanding group of
      children in WA. The results achieved by the SDS in WA demonstrate that a service
      based primarily on dental auxiliaries is viable and efficient.

PMID- 8536086
TI  - Familial and maternal factors affecting the dental health and dental attendance
      of preschool children.
AB  - Factors affecting the dental health and dental registration of preschool children
      were examined. Questionnaires were completed for 340 randomly selected children
      and the dental caries status of 294 of these children was examined. There was a
      statistically significant relationship between the dental caries experience of
      the child and its position in the family, the lowest caries experience occurring
      in the second and third born. The peak age of new dental registration appeared to
      occur during children's third year. The person responsible for bringing the child
      for dental appointments was the mother in 290 instances out of 340. Maternal
      education level was significantly associated with child dental health. The caries
      prevalence in children whose mothers were educated to 3rd level was 10.6 per cent
      as compared to 38.1 per cent for 2nd level and 46.8 per cent for below '0' level
      mothers. Mothers who were relaxed about their own dental care were the most
      likely to have preschool children who were registered for dental care. Similarly
      those mothers whose last dental visit occurred in the previous six months were
      the most likely to have children who were registered.

PMID- 8536087
TI  - Smart Habit Xylitol campaign, a new approach in oral health promotion.
AB  - A national 'Smart Habit' Xylitol campaign was organised in Finland in autumn
      1992. The aim of the campaign was to increase consumption of xylitol chewing gum
      in 13-year-old school children, to promote their oral health. The campaign was
      conducted in elementary schools in the form of a quiz and lesson related to
      xylitol. Seventh form children from schools in 12 local health authority areas in
      10 provinces took part in the campaign. Six thousand seven hundred children were
      involved. Data were collected with a series of three separate postal
      questionnaires. The study group consisted of 1,281 children exposed to the
      campaign. A control group was formed from 1,227 children in the same provinces
      not exposed to it. Questionnaires were distributed before and after the campaign.
      A third one was sent out a month later. A high number of the children had
      consumed xylitol chewing gum even before the campaign. The majority of the
      respondents reported no changes in consumption of xylitol chewing gum after meals
      in the first two questionnaires. The results showed that the consumption of
      xylitol chewing gum after meals increased more in the group exposed to the
      campaign than in the control group (P = 0.002). Girls in the study group
      increased their consumption of xylitol chewing gum more than boys (P = 0.016).
      Also an increase in the daily use of xylitol chewing gum was achieved by the
      campaign; differences between the study and the control group being significant
      (P < 0.05). Even though there was knowledge about the beneficial properties of
      xylitol beforehand, an increase in knowledge was achieved by the campaign. There
      seems to be potential for positive oral health promotion by means of this type of
      xylitol campaign.

PMID- 8536088
TI  - The role of the community pharmacist as a dental health adviser.
AB  - In this study 409 community pharmacists answered a questionnaire about the number
      and nature of their customers' inquiries regarding oral health and topics related
      to dentures. Three-quarters of respondents were asked, at least once a week, for
      advice on a wide range of such matters. The results indicate that pharmacists'
      knowledge is poor and it is therefore concluded that more material concerning
      oral health should be given in their undergraduate and postgraduate education.
      The general public would benefit substantially.

PMID- 8536089
TI  - A sequential modular curriculum for oral health personnel.

PMID- 8536090
TI  - Dental problems of a rural community in Sierra Leone.
AB  - As part of an undergraduate elective project, 56 villagers of all ages residing
      in a remote region of Sierra Leone were examined for caries and periodontal
      status. The results show moderate disease levels which increase with age. There
      is little evidence of provision of dental services. Although there is no sucrose
      available in the village, the diet includes a high fruit component which may
      cause dental caries. Physical and political access to the village may constrain
      proposed preventive oral health programmes.

PMID- 8536091
TI  - Maximising response to postal surveys of adult dental health.

PMID- 8536092
TI  - Heartstop: game of skill.

PMID- 8536093
TI  - Perseverance brings rewards.

PMID- 8536094
TI  - A compelling group of nurses.

PMID- 8536095
TI  - Dealing with the reforms.

PMID- 8536097
TI  - Safe practice and aromatherapy.

PMID- 8536096
TI  - Abusing the practice nurse subsidy.

PMID- 8536098
TI  - Number crunchers get their way.

PMID- 8536099
TI  - Patients suffer as nurses leave.

PMID- 8536100
TI  - Casual nurses meet a demand.

PMID- 8536101
TI  - Chemical caution.

PMID- 8536102
TI  - Increased soluble tumor necrosis factor receptor expression and release by human
      immunodeficiency virus type 1 infection.
AB  - High levels of circulating soluble tumor necrosis factor receptors (sTNF-R) are
      associated with HIV-1 infection and disease. To understand better this
      association, we have investigated p55 and p75 TNF-R expression on peripheral
      blood mononuclear cell (PBMC) subsets and in the promonocytic cell line U937,
      with or without HIV infection. Using flow cytometry and monoclonal antibodies
      both to sTNF-R and to PBMC subsets, TNF-R were found to be expressed mostly by
      monocytes and in decreasing amounts and intensity in the following order: CD14+
      cells > CD8+ cells > CD4+ cells. Expression of TNF-R was higher on cells obtained
      from HIV-infected than from noninfected subjects, and expression of p75 sTNF-R
      was much higher than that of p55 sTNF-R. Studying the U937 cells revealed that
      over 80% of the cells expressed both sTNF-R, but with greater fluorescence
      intensity in the HIV-1 chronically infected cells (U-937-IIIB). Treatment of the
      cells with PMA caused an accelerated release into the medium of both sTNF-R, with
      a sharp decline in their cell surface expression. Basal levels of mRNA
      transcripts for p75 TNF-R were higher in the U-937-IIIB cells than in the
      uninfected cells, but p55 TNF-R mRNA was expressed only in the HIV-1-infected
      cells. These findings show that HIV-1 infection is accompanied by predominant
      elevation of p75 TNF-R surface expression on monocytes and CD8+ lymphocytes, and
      results in both increased message and expression of these receptors in
      monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536103
TI  - Analysis of transforming growth factor beta and other cytokines in autoimmune
      exocrinopathy (Sjogren's syndrome).
AB  - Cytokines play a major role in tissue destruction caused by autoimmune
      dysregulation. In Sjogren's syndrome (SS) patients, salivary glands are the
      target organs for autoimmune tissue damage. In the present study, reverse
      transcriptase-polymerase chain reaction (RT-PCR) was used to look for cytokine
      mRNA expressed in SS salivary glands. Focus score was used to determine the
      severity of the lesions. Cytokine production in supernatants of the salivary
      gland cell culture was measured by enzyme-linked immunosorbent assay (ELISA).
      Immunohistochemical staining was used to identify the local presence of
      transforming growth factor beta (TGF-beta). Interleukin (IL)-2, IL-6, and IL-10
      mRNA were expressed in moderate to severe SS salivary gland lesions. TGF-beta
      mRNA was constitutively expressed in normal and SS salivary glands. In SS
      salivary gland cell cultures, IL-6 and IL-10 proteins were produced. TGF-beta
      production was reduced in high focus score SS glands. Normal and minimally
      involved SS salivary gland ductal epithelium and acinar cells were found to
      produce TGF-beta by immunostaining. In conclusion, an excess production of IL-2,
      IL-6, and IL-10 and a reduced production of the immunosuppressive cytokine, TGF
      beta, may be responsible for the progression of the salivary gland lesion in SS.
      Specific immunotherapy can now be designed based on mechanisms to correct this
      cytokine imbalance and benefit patients with autoimmune diseases, such as SS.

PMID- 8536104
TI  - Atypical spI interferon binds on porcine cells to a major component of type I
      interferon receptor.
AB  - The short porcine type I interferon (spI IFN), encoded by a gene physiologically
      expressed by the pig embryonic trophoblast during implantation, represents the
      first member of a novel family type I IFN. Binding and cross-linking experiments
      were carried out to characterize its cellular receptor. On porcine kidney cells,
      specific binding of 125I-spI IFN could be displaced significantly by spI IFN,
      rpIFN-alpha 1, and rhIFN-alpha 1, but not by rhIFN-alpha 2a or by rpIFN-gamma. On
      the other hand, all these type I IFNs but not rpIFN-gamma were capable of
      displacing bound 32P-hIFN-alpha A-P1 on these cells. Cross-linking data show that
      the specific 120 kD complex formed with these two radiolabeled ligands was
      displaceable by an excess of both spI IFN and rpIFN-alpha 1. These results
      provide primary evidence that spI IFN shares at least the major binding subunit
      of type I IFN receptor on porcine cells. On human WISH cells, 125I-spI IFN did
      not form any complex, nor did spI IFN affect cross-linking complexes of 32P-hIFN
      alpha A-P1 on these cells, unlike rpIFN-alpha 1. The lack of antiviral and
      antiproliferative effects of spI IFN on human cells is primarily a result of its
      inability to recognize human type I IFN receptor.

PMID- 8536105
TI  - Interferon-gamma affects protein kinase C activity in human neutrophils.
AB  - Interferon-gamma (IFN-gamma) is a priming agent of polymorphonuclear neutrophilic
      granulocyte (PMN) oxygen metabolism, and protein kinase C (PKC) is traditionally
      believed to play a central role in activation of this oxygen metabolism. In the
      present study, we have shown that the PKC activity in PMN is affected by IFN
      gamma. After only 2 minutes exposure to IFN-gamma (100 U/ml), PKC activity was
      significantly increased in the noncytosolic fraction of the cells. This increase
      was transient, but toward the end of the priming period of 2 h, the membrane
      associated PKC activity increased again to about 152% of control. In the
      cytosolic fraction, a small and hardly detectable decrease in PKC activity was
      observed. Treatment of PMN with granulocyte-macrophage colony-stimulating factor
      (GM-CSF), another PMN priming agent, showed no significant effects on the PKC
      activity. When the cells were stimulated with the bacterial peptide fMLP after a
      priming period with IFN-gamma or GM-CSF for 2 h, no significant difference
      between treated and control cells could be observed. PMN oxygen metabolism,
      measured by flow cytometry as an accumulation of the fluorescent compound
      dichlorofluorescein, was in these experiments significantly primed by IFN-gamma,
      both at baseline and when stimulated with fMLP. The protein kinase C inhibitors
      H7 and Ro31-8220 blocked the fMLP responses to some extent, but not completely.
      However, no significant difference between fMLP responses in control and IFN
      gamma-treated cells could be detected after administration of
      inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536106
TI  - Antiviral activity of autocrine interferon-beta requires the presence of a
      functional interferon type I receptor.
AB  - We and others have previously observed that the antiviral effects of autocrine
      interferon (IFN)-alpha/beta activity cannot be abolished by neutralizing
      antibodies, even when present to a large excess. This raises the possibility that
      the major part of autocrine activity is triggered intracellularly, possibly
      bypassing the transmembrane IFN-alpha/beta receptor. To examine this possibility,
      cells derived from IFN-alpha/beta Ro/o knockout mice lacking a functional IFN
      alpha/beta receptor were stably transformed with pHMB-KbMuIFN beta or pMFG-MuIFN
      beta plasmids encoding a constitutively expressed murine IFN-beta gene. Four
      different clones were isolated and examined for resistance to a retrovirus, MFG
      LacZ, and to Semliki Forest virus. Despite the production of autocrine IFN-beta
      at levels inducing high antiviral resistance in control cells, none of the clones
      displayed antiviral resistance. Thus, despite its failure to be neutralized by
      potent antiserum, the antiviral activity of autocrine IFN-beta takes place via
      the transmembrane IFN-alpha/beta receptor, and no additional pathway is involved.

PMID- 8536107
TI  - ADP-ribosylation inhibitors inhibit cellular RNA synthesis but do not affect
      expression of manganous superoxide dismutase or heat shock protein 70 in tumor
      necrosis factor alpha-sensitive and -resistant tumor cells.
AB  - We have shown that the cytotoxic response of TNF-sensitive L929 cells and TNF
      resistant EMT-6 cells to TNF-alpha can be modulated by ADP-ribosylation
      inhibitors independently of ADP-ribosylation rates. To explore the possibility
      that these inhibitors modulate TNF cytotoxicity by interfering with cellular
      protective mechanisms, we evaluated their effects on general RNA synthesis and on
      mRNA expression of two proposed protective genes, manganous superoxide dismutase
      (MnSOD) and heat shock protein 70 (hsp70). We found that ADP-ribosylation
      inhibitors could inhibit general RNA synthesis in a dose-dependent fashion to a
      similar extent in both EMT-6 and L929 cells, although these inhibitors increased
      or decreased the sensitivity of the cells to TNF, respectively. In EMT-6 cells,
      combination of actinomycin D with these inhibitors further inhibited the RNA
      synthesis rate, and it actually decreased the TNF sensitivity of the EMT-6 cells.
      Furthermore, the expression of MnSOD or hsp70 was not regulated by these
      inhibitors. Thus, TNF resistance must depend on other mechanisms in addition to
      the expression of these protective genes.

PMID- 8536109
TI  - Production of cytokines with antiviral activity by endothelial cells.
AB  - We compared the replication of VSV in human umbilical cord vein organ cultures
      (OC) with that in endothelial cells detached from the vein and infected
      immediately or infected after 24 h in culture. In four experiments of five, the
      virus titers obtained in the endothelial cells infected after 24 h in culture
      were 10-100 times higher than in the OC and 100-1000 times higher than in the
      freshly detached endothelial cells. To determine whether production of IFN, TNF,
      and IL-6 in the various cultures correlated with the data for virus yields, we
      measured the amounts of these cytokines formed. The OC produced considerably
      larger amounts of all of these. The endothelial cells produced very little IFN
      and TNF. Overall, there was no clear correlation between virus production and the
      amounts of these cytokines formed.

PMID- 8536108
TI  - Interferon regulatory factor element and interferon regulatory factor 1 in the
      induction of major histocompatibility complex class I genes in neural cells.
AB  - The role of the MHC-IRF-E and interferon regulatory factor 1 (IRF-1) in the
      regulation of MHC class I genes in astrocytes was analyzed. Transcriptional
      activation of MHC class I genes after treatment of astrocytes with various
      inducers occurred over a period of hours and correlated with cell surface
      expression. Functional analysis of the MHC class I gene promoter region confirmed
      that induction was controlled by a restricted region of 88 base pairs containing
      two well-defined inducible enhancers, the MHC-CRE and the MHC-IRF-E. Further
      analysis showed that potential MHC-CRE enhancer activity was silent. Therefore,
      the MHC-IRF-E, rather than the MHC-CRE, appeared responsible for enhancement of
      the MHC class I gene and was supported by three findings: (1) site-directed
      mutation of the MHC-IRF-E-abrogated induction, (2) promoter constructs containing
      IRF-Es as the sole enhancers were highly inducible in astrocytes, and (3) the
      expression of transcription factor IRF-1, which acts through the MHC-IRF-E to
      induce MHC class I genes, was induced to high levels in parallel with that of MHC
      class I induction. The induction of the IRF-1 gene correlated with the prior
      induction of the gamma-activated factor (GAF) or NF-kappa B, depending on the
      inducer, indicating that both gamma activation sites (GAS) and kappa B sites in
      the IRF-1 promoter are important.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536110
TI  - An Alu cassette in the cytoplasmic domain of an interferon receptor subunit.
AB  - All the cloned subunits of interferon receptors (IFNRs) belong to the type II
      cytokine receptor family (CRF2). Although three members of CRF2 encoded on human
      chromosome 21 share a 50 amino acid cytoplasmic homology domain (the IRH2
      domain), a fourth subunit, the second cloned chain of the type I IFNR (IFNIR-2),
      contains a juxtamembrane 20 amino acid stretch of high similarity to the IRH2
      domain that stops abruptly. Comparison of the membrane-distal portion of the
      IFNIR-2 cytoplasmic domain with sequence databases revealed a very high
      similarity to Alu repeat sequences. We provide evidence that all but 18 amino
      acids of the predicted cytoplasmic domain of the IFNIR-2 chain are encoded by an
      Alu cassette in its antisense orientation. Incorporation of an Alu cassette into
      the receptor chain is proposed to occur by a splicing mechanism. All previous
      well-characterized examples of insertion of an antisense Alu cassette into an
      open reading frame have involved alternative splicing. Thus, we predict the
      existence of an alternatively spliced product of the IFNIR-2 chain with a
      substantially different cytoplasmic domain.

PMID- 8536112
TI  - New models for emergency and ambulatory care at academic health centers--Part
      III: Boston and Alberta, Canada.

PMID- 8536111
TI  - Signaling by E-selectin and ICAM-1 induces endothelial tissue factor production
      via autocrine secretion of platelet-activating factor and tumor necrosis factor
      alpha.
AB  - Based on previous studies showed adhesion molecule-dependent induction of tissue
      factor upon endothelium-lymphocyte interactions, we investigated whether E
      selectin and ICAM-1 are linked to signaling pathways leading to tissue factor
      gene expression. Cellular interaction was mimicked by antibody cross-linking of E
      selectin and ICAM-1 on the surface of human umbilical vein endothelial cells
      (HUVECs), resulting in induction of tissue factor mRNA and protein expression.
      Tissue factor production could be independently abolished by antibodies against
      TNF-alpha and by WEB 2086, a platelet-activating factor (PAF) receptor
      antagonist. Because WEB 2086 prevented the production and/or secretion of TNF
      alpha by HUVECs, these results provide evidence for E-selectin- and ICAM-1-linked
      signal pathways leading to tissue factor synthesis in endothelial cells via an
      autocrine feedback loop involving PAF and TNF-alpha secretion.

PMID- 8536113
TI  - North Fork Research Park: a strategic alliance between the university and
      industry.

PMID- 8536114
TI  - Teaching Spanish.

PMID- 8536115
TI  - Purified protein derivative skin test policies and emergency medicine
      residencies.

PMID- 8536116
TI  - Vibrio vulnificus sepsis manifesting as compartment syndrome.

PMID- 8536117
TI  - Should we add an acid to an alkali injury? For now, let's remain neutral!

PMID- 8536118
TI  - Fenoldopam for hypertensive emergencies.

PMID- 8536119
TI  - Science as a means to health care reform.

PMID- 8536120
TI  - Effective treatment for acute alkali injury to the esophagus using weak-acid
      neutralization therapy: an ex-vivo study.
AB  - OBJECTIVE: 1) To evaluate whether neutralization therapy with weak acid is
      effective in reducing observed histopathologic esophageal tissue injury secondary
      to liquid alkali, 2) to quantify the temperature change of the neutralizing
      agent, and 3) to determine the effect of interval to therapy on injury severity.
      METHODS: Harvested Sprague-Dawley rat esophagi were catheterized and placed in an
      oxygenated saline bath (37 degrees C) for 60 minutes and then fixed in 10%
      formalin. Nine groups (n = 10) were perfused with 50% sodium hydroxide (NaOH).
      Six of the groups were treated by neutralization with cooled orange juice (OJ) or
      cola that was maintained between 2 degrees C and 4 degrees C. This was performed
      at 0, 5, or 30 minutes after injury. In addition, two positive control groups
      were exposed to OJ or cola at time 0 and were not exposed to strong alkali. A
      third control group was exposed to strong alkali but was not administered any
      subsequent treatment. The temperature of the neutralizing agent was recorded
      prior to instillation and after exiting the esophagus. Blinded pathologic scoring
      of 0 (no injury) to 3 (severe) was recorded performed for six histopathologic
      categories: epithelial cell viability, cornified epithelial cell differentiation,
      granular cell differentiation, epithelial cell nuclei, muscle cells, and muscle
      cell nuclei. Comparisons were made among treatment times using the Kruskal-Wallis
      test and linear trend analysis. RESULTS: For each histopathologic category and
      each treatment mode, the Kruskal-Wallis test showed significant differences
      between the groups (p < 0.002) over time. Trend analyses showed more severe
      injury with delayed neutralization therapy (p < 0.05) for each treatment mode and
      histopathologic category. CONCLUSION: Early neutralization therapy with OJ or
      cola reduces acute esophageal alkali injury. Additional in-vivo study is needed
      before neutralization therapy is adopted for clinical use.

PMID- 8536121
TI  - Randomized, prospective trial of fenoldopam vs sodium nitroprusside in the
      treatment of acute severe hypertension. Fenoldopam Study Group.
AB  - OBJECTIVE: To compare the safeties and efficacies of IV fenoldopam (FNP) vs
      sodium nitroprusside (NTP) in severe acute hypertension. METHODS: A prospective,
      randomized, open-label, multicenter international trial, at 24 academic medical
      centers, was conducted. The participants were adult patients (21-80 years of age)
      who had supine diastolic blood pressures (DBPs) > or = 120 mm Hg, were capable of
      written informed consent, and did not have selected exclusion criteria. The
      subjects were randomized to either FNP or NTP therapy; DBP was titrated to 95-110
      mm Hg, or a maximum reduction of 40 mm Hg for very high pressures. Infusions were
      maintained for at least six hours, then the patients were weaned off the IV
      therapy and oral medication was started. Measurements included BP, heart rate,
      and duration of study drug infusion and frequency of side effects or
      complications. RESULTS: A total of 183 patients (90 FNP, 93 NTP) were enrolled.
      Fifteen patients from each arm were excluded from efficacy analysis due to
      protocol violation. There was no significant difference in baseline
      characteristics. The two antihypertensive agents were equivalent in controlling
      and maintaining DBP. Systolic blood pressure (SBP) was reduced to a slightly
      greater degree for the NTP-treated patients during the initial (0.5-1-hr) study
      period, and both SBP and DBP were reduced more for the FNP-treated patients in
      the subset receiving infusions during the 12-24-hour period. The adverse effect
      profiles of the drugs were similar, as were the times to achieve target pressure,
      with no clinically relevant difference. CONCLUSIONS: For patients who had acute
      severe hypertension, FNP and NTP were equivalent in terms of efficacy and acute
      adverse events. Because of a unique mechanism of action, FNP may have advantages
      in selected subsets of patients. Further studies may be indicated in patient
      populations with pure "hypertensive emergencies."

PMID- 8536122
TI  - Use of radiography in acute knee injuries: need for clinical decision rules.
AB  - OBJECTIVES: To study: 1) the efficiency of the current use of radiography in
      acute knee injuries, 2) the judgments and attitudes of experienced clinicians in
      their use of knee radiography, and 3) the potential for decision rules to improve
      efficiency. METHODS: This two-stage study of adults with acute knee injuries
      involved: 1) a retrospective review of all 1,967 patients seen over a 12-month
      period in the EDs of one community and two teaching hospital, and 2) a
      prospective survey of another 1,040 patients seen by attending emergency
      physicians. The prospective survey assessed each clinician's estimate of the
      probability of a knee or patella fracture; 120 patients were independently
      assessed by two physicians. RESULTS: Of the 1,967 patients seen in the first
      stage, 74.1% underwent radiography but only 5.2% were found to have fractures. Of
      the 1,727 knee and patella radiographic series ordered, 92.4% were negative for
      fracture. In the second stage, experienced physicians predicted the probability
      of fracture to be 0 or 0.1 for 75.6% of the patients. The kappa value for this
      response was 0.51 (95% CI 0.34 to 0.68). The physicians also indicated that they
      would have been comfortable or very comfortable in not ordering radiography for
      55.5% of the patients. The area under the receiver operating characteristics
      curve for the physicians' prediction of fracture was 0.87 (95% CI 0.82 to 0.91),
      reflecting good discrimination between fracture and nonfracture cases. Likelihood
      ratios for the physicians' prediction ranged from 0.09 at the 0 level to 42.9 at
      the 0.9-1.0 level. CONCLUSIONS: Emergency physicians order radiography for most
      patients with acute knee injuries, even though they can accurately discriminate
      between fracture and nonfracture cases and expect most of the radiographs to be
      normal. These findings suggest great potential for more efficient use of knee
      radiography, possibly through the use of a clinical decision rule.

PMID- 8536123
TI  - Lack of a hyperkalemic response in emergency department patients receiving
      succinylcholine.
AB  - OBJECTIVE: To determine whether serum potassium (K) levels increase significantly
      following succinylcholine (SCh)-assisted intubation in ED patients. METHODS: A
      prospective, noncontrolled, consecutive case series design was used to evaluate
      the change in serum K levels in ED patients who received SCh for emergency
      intubation. The study was performed at an academic medical center staffed by
      board-certified emergency physicians. The subjects were 100 consecutive
      prescreened ED patients with various diagnoses who received SCh for intubation.
      The eligible subjects had serum K levels determined prior to and 5 minutes after
      administration of a 1.0-1.5-mg/kg i.v. dose of SCh. Serum K levels were measured
      by the ion-selective electrode assay method. RESULTS: The mean change in serum K
      levels was -0.04 mmol/L (95% CI -0.14 to 0.06). The maximum increase was 1.10
      mmol/L. The serum K level rose in 46 cases, decreased in 46 cases, and was
      unchanged in eight cases. No instance of SCh-induced cardiac arrest was
      identified. CONCLUSION: Changes in serum K levels following SCh administration in
      prescreened ED patients were minimal. A hyperkalemic response is uncommon in ED
      patients who undergo SCh-assisted intubation.

PMID- 8536124
TI  - Bedside fluoroscopy for the detection of foreign bodies.
AB  - OBJECTIVE: To determine the sensitivity and specificity of portable fluoroscopy
      for foreign-body detection using an ex-vivo experimental model. METHODS: A
      prospective, randomized masked investigation was performed to characterize
      foreign-body detection in cubes of beef. Three emergency physicians (EPs)
      independently used a portable fluoroscope to determine the presence or absence of
      various foreign bodies in ten cubes of beef (approximately 6 cm on each side).
      Six different groups of foreign bodies were examined: glass, wood, graphite
      (pencil lead), metal (needle), plastic, and gravel. An independent observer
      placed the six objects randomly into each set of ten beef cubes. One hundred
      observations were made by each physician using sets of ten beef cubes at a time.
      RESULTS: Fluoroscopy detected 117 of 180 foreign bodies (sensitivity 65%; 95% CI
      58-72%), including all cubes of beef embedded with gravel, metal, and glass.
      Graphite was detected 27 of 30 times (sensitivity 90%; 95% CI 74-98%). None of
      the plastic or wooden foreign bodies was identified despite magnification
      techniques and real-time imaging (sensitivity 0%; 95% CI0-12%, each). Of the 120
      cubes of meat with no foreign body, two false-positives were recorded
      (specificity 98%; 95% CI 94-100%). The overall positive predictive value and
      negative predictive value of fluoroscopy were 98% and 65%, with 95% CIs of 94
      100% and 58-72%, respectively. Interobserver agreement between the three EPs was
      considered excellent (kappa = 0.75). CONCLUSION: Bedside fluoroscopy lacks
      sufficient sensitivity to rule out many foreign bodies in the ED. Its use should
      be limited to suspected gravel, glass, pencil lead, and metallic objects, which
      are known to be radiopaque.

PMID- 8536125
TI  - Poor correlation of short- and long-term cosmetic appearance of repaired
      lacerations.
AB  - OBJECTIVE: To describe the consistency of a cosmetic scale for repaired
      lacerations and to determine whether the appearance of lacerations at the time of
      suture removal correlates with the appearance six to nine months later. METHODS:
      A convenience sample of patients who had lacerations repaired in a university
      teaching hospital were evaluated at the time of suture removal and six to nine
      months following repair. All lacerations were assigned 0 or 1 point each for the
      presence or absence of a step-off borders, contour irregularities, margin
      separation, edge inversion, excessive distortion, and overall appearance. A total
      cosmetic score (0-6) was calculated by adding the scores for the categories
      above. The consistency of the cosmetic scale was assessed by comparison of scores
      given by two different practitioners evaluating each patient at suture removal
      and long-term follow-up. The 38 evaluating practitioners were assigned based on
      availability and did not necessarily perform serial evaluations of the same
      patient. RESULTS: The 41 participating patients had a median age of 19 years
      (range, 2-82 years). Wounds were located predominantly on the head (73%) and
      upper extremity (22%). Long-term follow-up was performed at a median of 219 days
      (range, 155-280 days) after suture removal. Interpractitioner concordance
      regarding optimal appearance (score of 6 vs < or = 5) was moderate (kappa = 0.52)
      at the time of suture removal and substantial at the time of long-term follow-up
      (kappa = 0.68). However, the correlation of actual scores at the time of suture
      removal vs at long-term follow-up was poor (r = 0.17, p = 0.29). CONCLUSION: For
      our clinicians, the six-item categorical scale appears consistent as a tool for
      the assessment of the cosmetic appearance of wounds. However, correlation between
      laceration appearance at the time of suture removal and six to nine months later
      is poor.

PMID- 8536126
TI  - Right middle finger pain.

PMID- 8536127
TI  - Ethics of emergency department triage: SAEM position statement. SAEM Ethics
      Committee (Society for Academic Emergency Medicine).
AB  - Emergency department overcrowding, the growth of managed care, and the high cost
      of emergency care are creating pressures to triage patients away from U.S. EDs.
      Paradoxically, this pressure to limit patient access to EDs has increased in
      spite of federal laws that restrict patient triage and transfer. The latter
      regulations view EDs as the safety net for the U.S. health care system. The SAEM
      Ethics Committee evaluated the ethical implications of policies that triage
      patients out of the ED prior to complete evaluation and treatment. The committee
      used these implications to develop practical guidelines, which are reported.

PMID- 8536128
TI  - Sudden infant death syndrome--Part II: Etiologic theories.

PMID- 8536129
TI  - Intra- and interindividual variation in the pharmacokinetics of tacrolimus
      (FK506) in kidney transplant recipients--importance of trough level as a
      practical indicator.
AB  - BACKGROUND: Tacrolimus (FK506) is currently used as the primary immunosuppressant
      in clinical kidney transplantation in some centers. The purpose of this study was
      to evaluate the pharmacokinetics of this drug and to see if trough level, which
      has been used widely in therapeutic drug monitoring, can be used as an
      appropriate substitute for other pharmacokinetic measurement tests. METHODS: The
      blood concentration-time curve was studied in 10 kidney transplant recipients on
      26 occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood
      concentration was measured by two-step immunoabsorption assay. Methylprednisolone
      was used as a concomitant immunosuppressive drug. RESULTS: The blood
      concentration-time curves showed remarkable interindividual variation.
      Intraindividual variation was also found, but the degree of variation was slight
      compared with interindividual variation. On 17 occasions of measurement in one
      patient, the dose was significantly correlated with trough (r = 0.684), Cmax (r =
      0.838) and AUC0-12 (r = 0.817). In nine patients on nine occasions, however, the
      dose was not significantly correlated with trough (r = 0.351), Cmax (r = 0.270)
      or AUC0-12 (r = 0.355). tmax ranged from one to four hours (mean + SD; 2.8 + 1.3)
      and fluctuated in both intra- and interindividual measurements. In spite of a
      wide variation in the blood concentration-time-curve patterns, a highly
      significant linear relationship between trough and Cmax or AUC0-12 was observed
      in both intraindividual (Cmax, r = 0.876; AUC0-12, r = 0.926) and interindividual
      (Cmax, r = 0.943; AUC0-12, r = 0.984) measurements. CONCLUSIONS: We conclude that
      trough level is a practical acceptable indicator of the blood levels of
      tacrolimus, and can be used to monitor blood concentration.

PMID- 8536130
TI  - Prognostic significance of microvessel count in low stage renal cell carcinoma.
AB  - BACKGROUND: It has been postulated that tumors beyond a certain size are
      dependent on angiogenesis, which might also be related to distant metastasis. We
      therefore assessed the prognostic significance of tumor microvasculature in renal
      cell carcinoma. METHODS: Tumor specimens from 84 patients with primary renal cell
      carcinoma were examined by immunohistochemical staining for factor VIII.
      Individual microvessels were counted in a 200 x field overlying the area of
      highest neovacularization. RESULTS: The mean number of microvessels in patients
      with metastases was significantly higher than that in patients who were disease
      free for more than three years (P = 0.004). The survival of patients with less
      than 30 microvessels per 200 x field was significantly higher than that of
      patients with more than 30 microvessels per 200 x field (P = 0.007). Multivariate
      analyses revealed that these microvessel counts were the only significant
      predictor of prognosis in 45 patients with T1-2 and M0 tumors (P = 0.028).
      CONCLUSIONS: Assessment of tumor microvasculature is therefore probably one of
      the most important prognostic predictors in renal cell carcinoma.

PMID- 8536131
TI  - In situ perfusion by retrograde cannulation of a tumor artery for nephron-sparing
      surgery.
AB  - BACKGROUND: Although ice slush cooling or ex situ perfusion with bench surgery is
      most widely used for protecting ischemic renal damage which possibly accompanies
      complicated nephron-sparing surgery, each has its own disadvantages. The former
      does not allow excessively long ischemia and the latter requires complicated
      procedures as autotransplantation. In order to mitigate against these problems,
      we devised a novel method of in situ renal perfusion with intracellular
      hyperosmolar solution. METHODS: One renal segmental artery mainly supplying a
      tumor was isolated and cannulated with a small feeding tube. The tube was
      introduced through a small arteriotomy incision directed towards the proximal
      side, advanced until its tip remained in the main or first branch of the renal
      artery, and then it was anchored to that artery. After the main renal artery and
      vein were clamped, the kidney was perfused with cold Euro-Collins' solution
      through the tube, while the venous blood and perfusate were drained from the left
      gonadal vein or small venotomy incision of the right renal vein. RESULTS: In one
      case of renal cell carcinoma and three cases of angiomyolipoma, two of which
      ruptured, nephron-sparing surgery was carried out under in situ hyperosmolar
      perfusion. Ischemic time of these four cases was an average of 96 minutes,
      varying from 45 to 145 minutes. All the kidneys functioned well postoperatively.
      CONCLUSIONS: The method presented here is very simple, requires no unusual
      dexterity and safely allows for a long period of renal ischemia. This method is
      best indicated in cases where simple clamping of the renal pedicle with ice-slush
      cooling appears insufficient, yet ex situ surgery with autotransplantation seems
      excessive.

PMID- 8536132
TI  - Urinary immunoglobulins in patients with continent urinary reservoirs and ileal
      conduits.
AB  - BACKGROUND: Although bowel segments are commonly used for reconstructing the
      urinary tract, a high incidence of bacteriuria is observed in patients with
      urinary intestinal diversion. The normal gastrointestinal tract possesses a
      potent mucosal immune system characterized by secretory immunoglobulin A (sIgA)
      as the major humoral defense factor. However, the significance of urinary IgA
      secretion as the mucosal defense mechanism in patients with urinary intestinal
      diversion has remained obscure. In this study, urinary levels of sIgA as well as
      serum-type IgA were measured in patients with continent urinary reservoirs (Kock
      and Indiana pouches) and ileal conduits. METHODS: Twenty-four-hour urine samples
      were collected in a total of 80 patients with urinary intestinal diversion (22
      Kock pouch patients, 21 Indiana pouch patients and 37 ileal conduit patients).
      The amount of sIgA and serum-type IgA were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Urinary IgA levels showed great inter- and
      intra patient variability in all three groups. Indiana reservoir urine contained
      significantly greater amounts of sIgA (mean 32.0 mg/24 hrs) than Kock reservoir
      urine (11.9 mg) and conduit urine (4.9 mg), whereas Kock reservoir urine
      contained significantly more sIgA than conduit urine. However, the corresponding
      difference was not observed in regard to serum-type IgA. In none of the three
      modes of urinary diversion did 24-hour sIgA excretion show any correlation with
      the length of time after surgery. CONCLUSIONS: Since the amounts of sIgA in these
      patients were much greater than reported in urinary tract infection as well as in
      normal subjects, the major portion of urinary sIgA seemed to be secreted by the
      intestinal segments. Long-term sIgA secretion in urinary intestinal diversion,
      especially continent urinary reservoirs, may be an important host defense system.

PMID- 8536133
TI  - Augmentation duracystoplasty in neurogenic bladder dysfunction.
AB  - BACKGROUND: Augmentation cystoplasty is the treatment of choice for patients with
      neurogenic bladder dysfunction in cases that are unresponsive to other medical
      treatment. Although intestinal segments as bladder substitutes are preferred over
      the other alternatives at present, they are not ideal bladder replacements due to
      several potential hazards. The purpose of this study was to determine whether or
      not augmentation duracystoplasty can be an alternative to augmentation
      enterocystoplasties. METHODS: Ten patients with neurogenic bladder dysfunction
      unresponsive to conservative measures, underwent augmentation duracystoplasty by
      using the modified Bramble-Clam technique. The follow-up period was T-28 months.
      RESULTS: At present, seven of 10 patients are completely continent for with clean
      intermittent catheterization. The remaining three patients required oral
      oxybutinin therapy, postoperatively, to achieve continence although lower dosages
      than those required in the preoperative period. We did not observe any serious
      pre- or postoperative complications. CONCLUSIONS: Based on these preliminary
      findings we think that duracystoplasty can be considered as a treatment
      alternative for hyperreflexic and/or low compliant neurogenic bladders.

PMID- 8536134
TI  - Treatment of benign prostatic hyperplasia with high intensity focused ultrasound:
      an initial clinical trial in Japan with magnetic resonance imaging of the treated
      area.
AB  - BACKGROUND: High intensity focused ultrasound (HIFU) is a method of delivering
      acoustic energy to a focal point and is expected to induce tissue thermal
      ablation. Transrectal HIFU was applied to symptomatic benign prostatic
      hyperplasia (BPH) for relief of intravesical obstruction without injury to
      surrounding tissue. The clinical effectiveness and safety of transrectal HIFU
      were investigated. METHODS: Thirty-seven Japanese men with symptomatic BPH were
      treated with HIFU. The treatment was minimally invasive; operating time was less
      than 40 minutes, and a posttreatment indwelling catheter was left in place for 3
      4 days. RESULTS: The maximum urinary flow rate (ml. per second) increased from
      7.6 +/- 0.6 to 9.3 +/- 0.6 at three months in 37 patients (P < 0.05). During the
      same period the International Prostatic Symptom Score and Quality of Life score
      (points) decreased from 23.6 +/- 1.4 to 10.5 +/- 0.3, 5.2 +/- 0.3 to 2.6 +/- 0.1
      (P < 0.001), respectively. Overall response estimated by these three individual
      parameters were as follows; excellent 18.9%, good 48.6%, fair 10.8% and poor
      21.6% at three months. Magnetic resonance imaging using an endorectal coil showed
      coagulative necrosis defined in the therapy zone at one month after treatment.
      Side effects were transient urinary retention in six patients (16.2%), gross
      hematuria in four patients (10.8%) and hematospermia in four patients (10.8%).
      There was almost no intraoperative blood loss. CONCLUSIONS: Transrectal HIFU
      treatment of symptomatic BPH is safe, reduces symptoms significantly, and leads
      to a slight increase in uroflow.

PMID- 8536135
TI  - High intensity focused ultrasound for benign prostatic hyperplasia.
AB  - BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold
      standard of treatment for patients with symptomatic benign prostatic hyperplasia
      (BPH). The present paper discusses the safety and effectiveness of transrectal
      high intensity focused ultrasound (HIFU) for treating patients with symptomatic
      BPH. METHODS: HIFU was conducted on 28 patients with BPH. At one, three and six
      months after treatment, all patients were examined for parameters including
      International Prostate Symptom Scores (I-PSS), Quality of Life (QOL) inquiry,
      uroflowmetry, and transrectal ultrasound for determining prostate volume.
      RESULTS: I-PSS and QOL showed statistically significant improvement at one,
      three, and six months postoperatively (P < 0.0001-0.005, Wilcoxon signed-rank
      test). Ten of 28 (35.7%), 13 of 28 (46.4%), and 6 of 15 (40.0%) cases were
      categorized as effective cases with HIFU treatment at one, three, and six months
      follow-up. CONCLUSIONS: Focused ultrasound is an exciting new technology by which
      tissue can be destroyed at a site distant from the source of energy without
      damage to surrounding tissue. Clinical experience with alternative power
      settings, more accurate spacing of treatment lesions, and further development of
      HIFU machines may improve the results. Longer follow-up of patients with further
      clinical evaluation of HIFU is necessary to define the efficacy of this
      technique.

PMID- 8536136
TI  - Increasing the thermal dose in transurethral microwave thermotherapy produces no
      improvement in therapeutic efficacy.
AB  - BACKGROUND: Transurethral microwave thermotherapy (TUMT) is a minimally invasive
      treatment for benign prostatic hyperplasia (BPH). It has been reported that
      increased thermal dose and higher intraprostatic temperatures resulted in
      improved clinical response. Recently we treated BPH patients with the prostatron
      device using a new version of software (Prostasoft 2.5), which was intended to
      increase thermal delivery by allowing maximum power up to 70W. The safety and
      clinical results were compared between the patients treated with Prostasoft 2.5
      and those treated with the currently available software (Prostasoft 2; maximum
      power up to 50W). METHODS: A total of 105 patients were treated successively with
      two treatment protocols. Sixty-three patients were treated with Prostasoft 2
      between September 1992 and July 1993, while 42 were treated with Prostasoft 2.5
      between August 1993 and April 1994. Therefore, this investigation was a
      retrospective nonrandomized study. There was no significant difference in the
      baseline patient characteristics between the two groups. RESULTS: Total thermal
      dose delivered to the prostate was significantly higher in the Prostasoft 2.5
      group than that in the Prostasoft 2 group (137 kJ versus 116 kJ, P < 0.05). No
      serious complications were encountered in either group. Six months after TUMT, in
      both the Prostasoft 2.5 and Prostasoft 2 groups there was an improvement in
      patient condition as measured by the mean I-PSS, QOL, and peak flow rate values,
      as well as the overall therapeutic efficacy. The two groups differed in the
      amount of posttreatment improvement from between 8% and 22%, but this difference
      was not statistically significant. CONCLUSIONS: Our study suggests that higher
      thermal dose attained by Prostasoft 2.5 does not necessarily result in more
      pronounced clinical improvement, although clinical response to TUMT has often
      been reported to be dependent upon thermal dose.

PMID- 8536137
TI  - Epidemiological characteristics of prostate cancer in Gunma Prefecture, Japan.
      Gunma University Urological Oncology Study Group.
AB  - BACKGROUND: Prostate cancer is rare in Asia, but the number of patients is
      increasing in Japan. We conducted an epidemiological study of prostate cancer in
      Gunma Prefecture, Japan, to investigate the trends and characteristics of the
      disease. METHODS: The subjects were 1,411 prostate cancer patients newly
      diagnosed between 1985 and 1992, and 656 patients who died from prostate cancer
      between 1981 and 1992. The incidence and mortality rates were calculated by year,
      demographic region and age. RESULTS: The yearly incidence rate showed an increase
      but the mortality rate showed no marked fluctuations. There was no significant
      difference between urban and rural districts in either incidence or mortality
      rate. The incidence rate tended to be high in the northern part of the
      prefecture, but no marked variation in mortality rate was seen. The incidence and
      mortality rates in districts with a history of manganese mining were high
      compared to those in districts without mining. In contrast, the incidence and
      mortality rates in districts with a history of zinc mining were comparatively
      lower. Both incidence and mortality rates showed a marked increase with age. The
      age-specific incidence showed a double logarithmic relationship to age.
      CONCLUSIONS: The increase of the yearly incidence rate might be due to changes in
      lifestyle and environmental factors, improved diagnostic techniques, and
      increased awareness among the general public regarding prostate disease. Further
      investigation is needed to clarify the pattern and the causes of regional
      differences in the incidence and mortality rates. The possibilities that
      managanese and zinc might be related to prostatic carcinogenesis are suggested.

PMID- 8536138
TI  - The three-circle single J catheter: a more stable urethral catheter for pressure
      flow studies.
AB  - We describe a single J urethral catheter which has been specially designed to
      facilitate stabilization during voiding in pressure flow studies. It has a tip
      with three circles, which prevents the catheter from slipping out even when there
      is a sudden increase in intra-abdominal pressure.

PMID- 8536139
TI  - Laparoscopic gonadectomy for testicular feminization syndrome.
AB  - Laparoscopic gonadectomy was performed on a patient with complete androgen
      insensitivity (testicular feminization syndrome). In the case presented here,
      although the gonads were free, the omentum which was adhering to the right
      inguinal ring, possibly as a result of previous inguinal hernia repair, obscured
      the right gonad. The left gonad was located behind the sigmoid colon. We present
      our laparoscopic experience in managing this case of testicular feminization
      syndrome.

PMID- 8536140
TI  - Proliferating cell nuclear antigen in ACTH-independent bilateral macronodular
      adrenal hyperplasia.
AB  - ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH) has been
      recently described as a rare cause of Cushing's syndrome and it is an unusual
      process of unknown etiology. This report describes a case of a 59-year-old man
      with AIMAH. The proliferating cell nuclear antigen (PCNA) has been implicated in
      the process of cell proliferation and is detectable throughout most of the cell
      cycle. This report also describes the expression of PCNA in AIMAH by
      immunohistochemical staining. Most of the positive expression was seen in the
      greater part of the epithelial cells of the cortical lesion, but not in the
      interstitial cells. These data suggest that some effective factor, specific for
      adrenal cortical cell growth, might be produced in AIMAH.

PMID- 8536141
TI  - Lobar dysmorphism of the kidney.
AB  - We report a case of a 38-year-old woman with lobar dysmorphism of the kidney.
      Lobar dysmorphism is a pathology classified under renal pseudotumor, which has
      received little attention. It is presumed that these cases will increase in
      number with advances in imaging diagnosis. Dynamic CT scan is useful for the
      diagnosis of this disease.

PMID- 8536143
TI  - A case of Gartner's duct cyst with a right aplastic kidney.
AB  - We report a case of a Gartner's duct cyst with a right aplastic kidney. This was
      discovered when the right kidney was not identified in an examination for
      epigastric pain. CT and MRI proved useful in the diagnosis. An MRI showed a
      tubular structure ascending from the cyst and a complication of a bicornate
      uterus. As the patient was asymptomatic, the patient was followed without
      treatment.

PMID- 8536142
TI  - Renal cell carcinoma with synchronous bilateral adrenal metastases.

PMID- 8536144
TI  - Physical activity and cardiovascular risk.

PMID- 8536145
TI  - Epidemiology of physical activity, physical fitness and coronary heart disease.
AB  - Observational population-based studies have consistently shown an inverse dose
      response gradient between physical activity or fitness and coronary heart
      disease. This relationship is more firmly established in men. Existing studies
      suggest that the physical activity gradient, and perhaps the fitness gradient, is
      produced by a combination of varying levels of both the intensity and the amount
      of habitual physical activity. It is not at present possible to definitively
      describe the dose-response association between the intensity of physical activity
      and the risk of coronary heart disease. An answer to this important question
      awaits further research.

PMID- 8536146
TI  - Does exercise training play a role in the treatment of essential hypertension?
AB  - Endurance exercise training reduces systolic and diastolic blood pressures in
      approximately 75% of people who have essential hypertension; these reductions are
      approximately 10 mmHg for both systolic and diastolic blood pressures. Exercise
      training at intensities of 40-70% VO2max appears to lower systolic blood pressure
      somewhat more and diastolic blood pressure to the same degree as higher-intensity
      training. Additional benefits of endurance exercise training on other risk
      factors for coronary heart disease make such training an efficacious intervention
      for people who have mild-to-moderate elevations in blood pressure.

PMID- 8536147
TI  - Influence of exercise on insulin sensitivity.
AB  - An important determinant of insulin sensitivity in humans, the insulin-induced
      glucose uptake in skeletal muscle (directed into glycogen synthesis), has been
      found to be markedly enhanced in endurance-trained individuals compared with
      sedentary controls. This enhanced insulin action is accompanied by a decreased
      insulin response during an oral glucose load. Available evidence indicates that
      the enhanced insulin action is not a genuine training effect, but merely a
      lasting effect of the previous exercise session(s). In the young, insulin
      sensitivity increases with a single exercise session, but the increase may appear
      only after several training sessions in middle-aged or older individuals. The
      effect disappears after 3-6 days. The exercise-induced reduction in muscle
      glycogen is an important factor underlying the increased insulin sensitivity in
      the period after exercise. There are reports that endurance and strength training
      enhances whole-body insulin sensitivity to a similar extent, and available
      evidence suggests that, provided total energy expenditure is held constant, low
      intensity and high-intensity exercise are equally effective in promoting insulin
      sensitivity. Differences in sex steroids may explain the observation of a
      markedly higher insulin sensitivity in women than in men. Adaptations, which
      might underlie the increased insulin sensitivity in trained individuals, include
      increases in levels of the glucose transporter protein GLUT-4 and in muscle
      glycogen synthase activity, a decrease in the serum triglyceride concentration
      and, possibly, an increase in the muscle capillary network.

PMID- 8536148
TI  - Exercise and lipoprotein metabolism.
AB  - Physical activity can have a significant effect on plasma lipoproteins and
      lipoprotein metabolism. The effect of exercise on lipoprotein subclasses is often
      more significant than is reflected by routine measures of lipoprotein
      cholesterol. These effects have important clinical implications. Some
      apolipoprotein levels, with the exception of those of lipoprotein (a), are
      affected by physical activity. Changes in enzymes, as well as transfer protein,
      activity can help explain the exercise-induced changes in lipoprotein levels.
      Understanding the complex interaction between exercise and lipoprotein metabolism
      will enable the therapeutic use of exercise in the appropriate patient
      population.

PMID- 8536149
TI  - Exercise and postprandial lipaemia.
AB  - Postprandial hyperlipidaemia is a risk factor for atherosclerosis in multiple
      vascular beds, independently of high-density lipoprotein (HDL) cholesterol. An
      increased level of HDL cholesterol is a strong indicator of a low risk of
      atherosclerosis. Exercise decreases postprandial lipaemia and, in turn, increases
      levels of HDL cholesterol. The favourable effects of exercise on lipoprotein
      metabolism, particularly evident in the postprandial state, may thus help to
      decrease susceptibility to atherosclerosis in exercise-trained people.

PMID- 8536150
TI  - Exercise and haemostatic function.
AB  - To reduce the risk of ischaemic heart disease, vigorous exercise has to be
      maintained over time. This suggests that the benefit is at least partly due to a
      short-term effect, such as an influence on the haemostatic system and
      thrombogenic potential. A high plasma fibrinogen level is strongly and
      independently associated with the incidence of ischaemic heart disease, and the
      effects of exercise on fibrinogen have now been extensively investigated. One
      randomized controlled trial and several large epidemiological studies show that
      vigorous exercise lowers the plasma fibrinogen level by an amount that would
      reduce the risk of ischaemic heart disease by 7 or 8% on a conservative estimate,
      along with additional benefits due to any favourable effects on blood pressure
      and lipids, for example. However, unaccustomed exertion raises the immediate risk
      of ischaemic heart disease probably, at least in part, through a short-term
      increase in coagulability. Thus, those who are not accustomed to physical
      exertion should approach it gradually in the early stages of exercise programmes.

PMID- 8536151
TI  - An acidic kininogenase in rat ventricular myocardium.
AB  - BACKGROUND: Canine ventricles have been reported to contain a cathepsin D-like
      kininogenase, which might confer protection on the heart during ischaemia. The
      aim of this study was to investigate the presence and levels of a similar
      kininogenase in normal and ischaemic rat hearts. METHODS: Aqueous extracts of rat
      ventricles were tested for the ability to release bradykinin-like
      immunoreactivity from human low-molecular-weight kininogen and high-molecular
      weight kininogen at acidic pHs. The enzymes involved were separated using gel
      filtration followed by the testing of fractions for cleavage of D-Val-Leu-Arg-pNA
      and low-molecular-weight kininogen. Extracts from normal and ischaemic ventricles
      were compared for the ability to release bradykinin-like immunoreactivity from
      low-molecular-weight kininogen. Kinin levels in mixed venous blood were compared
      before and after ischaemia. By assessing their effect on isolated oestrous rat
      uteri and on protease inhibitors, further characterization of acidic
      kininogenases in the extracts was performed. RESULTS: Extracts of rat ventricles
      released bradykinin-like immunoreactivity only from low-molecular-weight
      kininogen. Using the isolated oestrous rat uterus, gel filtration and protease
      inhibitors, the enzyme involved was identified as a cathepsin D-like enzyme with
      an optimum pH of 4.7 and a molecular weight of 42.8 +/- 4.9 kDa. It is an
      arginine amidase and releases bradykinin-like immunoreactivity from low-molecular
      weight kininogen. Ischaemia reduced the amount of bradykinin-like
      immunoreactivity released by the ventricular extract (P < or = 0.05) and
      increased levels of free kinin in venous blood from the right atrium. CONCLUSION:
      Rat ventricles contain a cathepsin D-like acidic protease that cleaves low
      molecular-weight kininogen to release bradykinin-like immunoreactivity. The
      acidic protease may protect the heart during ischaemia.

PMID- 8536152
TI  - Elevated insulin levels in men: an 11-year follow-up study.
AB  - BACKGROUND: Hyperinsulinaemia is linked to cardiovascular disease. This follow-up
      study examines factors influencing the fasting insulin level in men. METHODS: All
      men born in 1936 living in a certain area within the county of Copenhagen were
      invited for a health examination in 1976 and 1987; 425 men (73%) participated in
      both examinations. The following variables were analysed: fasting insulin levels,
      body mass index (BMI), fasting blood glucose, physical activity during leisure
      time, alcohol consumption and smoking. RESULTS: In both multivariate analyses at
      age 40 years and age 51 years, the BMI, the fasting glucose level and lack of
      physical activity showed a positive independent association with the insulin
      level. In follow-up analyses over 11 years, only BMI changes and fasting glucose
      changes were associated with changes in insulin level. CONCLUSIONS: Our analyses
      suggest that BMI and changes in BMI over a period of time are major risk factors
      for an elevation of the serum insulin level, but that physical activity may have
      beneficial effects on the insulin level.

PMID- 8536153
TI  - Effect of smoking on sudden and premature death.
AB  - BACKGROUND: Smoking has been related to coronary heart disease, and, in men, to
      sudden death. The results of a case-control study designed to assess the
      relationship between smoking and all causes of sudden and premature death are
      reported. METHODS: A questionnaire on the previous history and causes of death of
      all people buried in the Municipal Cemetery of Valencia (1986-1987) was
      administered to the relatives of the deceased. Among 4718 deaths, 284 victims of
      sudden death were identified, and 495 people who had not died suddenly were
      randomly sampled as controls. RESULTS: The proportion of smokers among the women
      studied was extremely low in contrast to 58.9% of men in the sudden death study
      group and 59.2% of men in the non-sudden death study group who smoked. Smokers
      died on average 10 years younger than non-smokers in the sudden-death group (63.3
      +/- 12.3 and 73.3 +/- 11.0 years respectively; P < 0.001), and 8 years earlier in
      the non-sudden death group (68.5 +/- 13.3 and 76.8 +/- 13.2 years, respectively;
      P < 0.001). A logistic regression model showed that smokers had an adjusted
      relative risk of 0.81 for sudden death compared with non-smokers (95% confidence
      interval [CI]: 0.45-1.46). Smokers 65 years of age or under had a 2.7 times
      greater risk (95% CI: 1.49-5.04) of premature death than non-smokers. Similar
      results were found in patients from the coronary- and cardiac-death subgroups.
      CONCLUSIONS: Smoking is an independent risk factor for premature death but not
      for sudden death.

PMID- 8536154
TI  - Do risk factors change in men at high risk of coronary heart disease?
      Observations on the effect of health promotion in primary care.
AB  - BACKGROUND: There has been an increasing focus on the identification and
      modification of risk factors for coronary heart disease (CHD) in primary care.
      One approach is to concentrate activity on those at high risk of CHD. METHODS:
      This study was a prospective follow-up after CHD risk assessment and intervention
      designed to determine whether middle-aged men identified as being at high risk of
      CHD in primary care, who participated in a randomized controlled trial of
      antithrombotic medication, reduced their risk factor profile in response to the
      health promotion given in all practices, whatever their treatment allocation. We
      studied 4316 men aged 45-69 years (who had not suffered a previous myocardial
      infarction or stroke) identified at screening in 81 general practices in the UK
      as being at high risk of coronary heart disease. The changes in the prevalence of
      smoking and in blood pressure, serum cholesterol level, body mass index and
      plasma fibrinogen level were recorded for a period of up to 2 years after entry
      into the trial. The use of standard health education materials and of more
      intensive individual interventions was substantial. There were regular
      opportunities through nurses and consultations with general practitioners for
      continuing advice about risk factors. RESULTS: The prevalence of current smoking
      fell during the trial but it was still 37% at 2 years. There was a significant
      decrease in blood pressure due first to regression to the mean but then to the
      trial's treatment protocol and accommodation to measurement. There were small
      falls between screening and entry in body mass and levels of serum cholesterol
      and fibrinogen, again due largely to regression to the mean; subsequent changes
      in these characteristics were negligible. CONCLUSION: Sustained and quite
      intensive health promotion activity had only a limited effect in men identified
      as being at high risk of CHD. In particular, there was little change in body mass
      or serum cholesterol. Although improved blood pressure control and a moderate
      reduction in the prevalence of smoking can be achieved, further research is
      needed to determine the most effective methods of risk factor reduction in order
      to realize the full potential of the 'high-risk' approach to the prevention of
      CHD.

PMID- 8536155
TI  - Comparison of two scoring systems used to monitor diets in outpatient clinical
      trials.
AB  - BACKGROUND: Dietary stability and compliance are crucial to the proper
      interpretation of the results of clinical trials evaluating the efficacy of lipid
      lowering drugs since dietary variations can obscure the true effects of the drugs
      being tested. Documentation of compliance to National Cholesterol Education
      Program (NCEP) dietary guidelines can be difficult to obtain, however, especially
      since many diets may meet one or two but not all the criteria for a Step 1 or 2
      classification. The purpose of this study was to compare the ability of two diet
      scoring systems (the Food Record Rating [FRR] and the Ratio of Ingested Saturated
      fat and Cholesterol to Calories [RISCC]) to classify these ambiguous diets.
      METHODS: Three-day diet diaries (n = 622) were obtained from patients
      participating in a multicenter, clinical trial testing the lipid-lowering effects
      of a fiber supplement. The FRR score of each diary was calculated; the diary was
      then computer analyzed for nutrient composition, and the RISCC score was
      calculated. Based upon the NCEP dietary criteria for total fat, saturated fat,
      and cholesterol each diet was classified as either Step 1 or Step 2. Diets
      exceeding Step 1 criteria were classified as typical American (Step 0). Diets not
      meeting all 3 criteria for any given Step were considered 'NCEP unclassifiable'.
      Using the FRR and RISCC scores of only the NCEP-classifiable diets, the optimal
      RISCC and FRR cutoff points to distinguish between Step 0 and 1 diets and Step 1
      and 2 diets were determined. RESULTS: Only 50% of the diets were NCEP
      classifiable. Using these diets, a RISCC of 20 best distinguished a Step 0 from a
      Step 1 diet, and 13 segregated Step 1 from 2 diets. The FRR cutoff points were 14
      and 8, respectively. Using these values, the RISCC was able correctly to classify
      92-97% of the diets, whereas the FRR correctly classified only 73-80%.
      Variability of scores within each Step was twice as high for the FRR as for the
      RISCC. The FRR was more biased by total kilocalories than was the RISCC.
      CONCLUSION: We conclude that the RISCC scoring system was more accurate and
      precise than the FRR system for diet classification, and was a superior tool for
      classifying the ambiguous diets. Since the RISCC also requires (and therefore
      provides) quantitative nutrient data and the FRR does not, the former is a better
      dietary monitoring tool for clinical trials.

PMID- 8536156
TI  - Bibliography of the current world literature.

PMID- 8536157
TI  - Sham feeding disrupts phase III of the duodenal migrating motor complex in
      humans.
AB  - The role of the vagus nerve in the control of the intestinal migrating motor
      complex (MMC) is unclear. This study aimed to evaluate the effect of
      physiological vagal stimulation with sham feeding on phase III of the MMC.
      Antroduodenal motility was recorded in six healthy volunteers. The first phase
      III was used as a control, and sham feeding was performed during the second phase
      III. The MMC was disrupted within 1.5 +/- 0.4 min of sham feeding and its
      duration was shorter than the control phase III. Phase III propagation was
      inhibited in all subjects, most of them exhibiting no propagation beyond the
      third duodenal recording site. During sham feeding, the antrum exhibited
      transient phasic contractions in five out of six subjects. The duodenal motility
      index recorded for up to 30 min after the onset of the sham feeding was unchanged
      in five out of six subjects. We conclude that sham feeding consistently
      interrupted phase III of the duodenal MMC and induced antral contractions, but
      failed to provoke significant motor events in the duodenum.

PMID- 8536158
TI  - Gallbladder motility before and after Billroth II gastric resection.
AB  - The aim of this study was to determine the effect of Billroth II gastric
      resection (BII) without vagotomy on gallbladder contraction in response to meal
      and CCK-OP infusion. Fourteen duodenal ulcer patients were studied before surgery
      and six months postoperatively. Gallbladder volume was measured by real-time
      ultrasonography. After surgery, there was a significant increase in fasting
      gallbladder volume (P < 0.05). Postprandial gallbladder emptying was not
      significantly affected by gastrectomy apart from a trend towards a shorter t1/2
      and a larger ejection volume. In addition, postoperative gallbladder relaxation
      was more pronounced at time 120 min. In response to cholecystokinin-octapeptide
      (CCK-OP) infusion, there was a significant decrease of t1/2 after BII and a
      prolonged contraction with a significantly reduced gallbladder volume. Our data
      show that the gallbladder response both to meal and CCK-OP infusion is modified
      after BII and a larger postoperative gallbladder volume may play a role in the
      pathogenesis of gallstone disease after gastric surgery.

PMID- 8536159
TI  - Intralipid-induced gastric relaxation is mediated via NO.
AB  - In vitro, nitric oxide (NO) has been shown to be the neurotransmitter responsible
      for gastric relaxation. In vivo gastric relaxations can be controlled via reflex
      pathways originating in the duodenum. The aim of this study was to determine
      whether NO was involved in gastric relaxation in vivo in conscious dogs induced
      by intraduodenal administration of intralipid. Gastric tone was monitored with a
      flaccid bag introduced into the stomach via a gastric cannula and connected to a
      barostat. Intralipid administration into the duodenum caused a gastric relaxation
      (420 +/- 11 ml, n = 6) sensitive to inhibition by nitro-L-arginine (L-NNA) (5 mg
      kg-1 i.v.). This inhibitory effect of L-NNA was reversed by L-arginine (100 mg kg
      1 i.v.). IN CONCLUSION: intraduodenal administration of intralipid induces a
      gastric relaxation via a NO-dependent mechanism.

PMID- 8536160
TI  - Electrical slow wave activity of the cat stomach: its frequency gradient and the
      effect of indomethacin.
AB  - The present study was performed to establish the intrinsic frequency of the slow
      waves in different regions of the cat stomach, to define the propagation velocity
      of the slow wave along the stomach, and to determine whether endogenous
      prostaglandins can affect the slow wave frequency. In 20 cats, electrical
      activity was recorded from the anterior wall of the intact stomach in vivo and in
      vitro, and in vitro after cutting the stomach into 16 pieces to isolate each pair
      of electrodes. In vivo, slow waves (4.1 +/- 0.5 cpm) were seen only from mid
      corpus to pylorus, the apparent propagation velocity decreasing towards the
      antrum. In vitro: (a) after cutting, the slow wave frequency increased, to a
      maximum in 1 h (12 +/- 1.8 cpm; range 10.2-17.3), with the highest frequency
      always in the mid or orad corpus, usually on the greater curvature (GC), (b) with
      indomethacin (10(-5) M) the increase in slow wave frequency was prevented or
      reversed, and there was a frequency gradient with the highest frequency (4.4 +/-
      1.2 cpm) uniformly located in the most proximal active site on the GC, and (c)
      slow waves on the GC were more stable, regular and continuous than on the lesser
      curvature (LC), the difference being most evident in the corpus. The results
      suggest that the cat stomach behaves as a system of electrically coupled
      oscillators of different frequencies. The dominant oscillator of highest
      frequency is situated in the proximal corpus of the GC, with the remainder of the
      distal stomach entrained at this frequency. All gastric slow wave oscillators can
      be driven to higher frequencies by endogenous prostaglandins. The decreasing
      velocity of slow wave propagation distally suggests that oscillator properties
      and/or coupling among oscillators differs in the cat.

PMID- 8536161
TI  - Postural changes in proximal gastric volume and pressure measured using a gastric
      barostat.
AB  - A barostat was used to examine the effect of changes in posture on the volume and
      pressure in a bag positioned in the proximal stomach of 14 normal volunteers.
      Volumes in the supine position were compared with those in the standing, left
      lateral and right lateral positions at a constant pressure 2 mmHg above basal
      intragastric pressure. A separate series of measurements was then used to
      evaluate the effects of the same postural changes on pressure within the bag
      whilst its volume was kept constant. Changing from the supine to the left lateral
      position decreased bag volume by 62% when pressure was controlled; pressure
      increased by 60% when volume was controlled. In contrast, movement from the
      supine to the right lateral position resulted in a 68% increase in bag volume and
      a 31% fall in pressure. Moving from supine to standing had inconsistent effects
      on bag volume and pressure. There was a negative correlation between the
      magnitudes of the changes in pressure and volume (r2 = 0.557). The observed
      effects of posture probably result from changes in the compression of the stomach
      by abdominal viscera and indicate that subject position must be specified and
      maintained constant in studies of proximal gastric motor function using a
      barostat.

PMID- 8536162
TI  - The effect of octreotide on human gastric compliance and sensory perception.
AB  - Somatostatin or its analogue octreotide (OCT) has previously been shown to
      modulate gastric emptying, intestinal motor activity and visceral sensation. In
      the current study we sought to determine the effect of a single dose of OCT (1.25
      micrograms kg-1 s.c.), which has previously been shown to have both motor and
      sensory effects, on proximal gastric compliance and on conscious perception of
      gastric distention. Gastric distention was performed in 13 healthy male
      volunteers, by either slow ramp distention (60 ml min-1) or by intermittent
      pressure steps (phasic distention; 4-20 mmHg) using an electronic distention
      device. Compliance curves (pressure-volume relationship), and thresholds for
      innocuous (fullness) and noxious sensations (discomfort, pain) were determined
      following vehicle or OCT injection. OCT consistently and significantly reduced
      the rate of the gastric accommodation reflex by 50%, resulting in a reduced
      compliance at distention pressures greater than 10 mmHg during phasic distention.
      In contrast, no effect was observed on the compliance curve obtained during ramp
      distention. OCT selectively increased the threshold for fullness during both ramp
      and phasic distention. During phasic distention, OCT decreased the volume
      thresholds for noxious (pain) sensations experienced at volumes greater than 300
      ml, without affecting the corresponding pressure threshold. These findings
      suggest that at low distension volumes, OCT in the dosage used has a direct
      inhibitory effect on afferents mediating innocuous gastric sensations. The
      hyperalgesic effect observed during phasic distention may be secondary to OCT's
      inhibitory effect on the gastric accommodation reflex.

PMID- 8536163
TI  - Evidence for mast cell, leukotriene and nitric oxide involvement in the
      regulation of the adrenoceptor number of inflamed small intestine in guinea pigs.
AB  - Changes in the populations of neurotransmitter receptors involved in the control
      of intestinal smooth muscle function have been associated with the altered
      motility of the inflamed gut. Thus, trinitrobenzenesulphonic acid (TNBS)-induced
      gut inflammation is accompanied by an increase in alpha- and a decrease in beta
      adrenoceptor numbers in guinea pig small intestine. In the present study, we
      investigated the effects of anti-inflammatory compounds (cyclooxygenase inhibitor
      indomethacin, lipooxygenase inhibitor MK-886, nitric oxide synthase inhibitor NG
      nitro-L-arginine methylester (L-NAME), mast cell stabilizer doxantrazole) on TNBS
      induced adrenoceptor changes. Smooth muscle adrenoceptor populations, labelled by
      subtype-specific radioligands 6 days after TNBS, were significantly different
      from those of sham-treated controls: alpha 1- and alpha 2-adrenoceptor numbers
      increased by more than 50%, while beta-adrenoceptor numbers decreased by more
      than 50%. These changes, associated with severe inflammation as assessed
      histologically and by myeloperoxidase assay, were prevented by doxantrazole or L
      NAME, and only partly by MK-886. In contrast, indomethacin did not prevent these
      changes. It appears then that: (a) mast cell mediators, nitric oxide and
      leukotrienes are likely to contribute to TNBS-induced changes in adrenoceptor
      populations in the guinea pig inflamed intestine; (b) there is no evidence for
      prostanoid involvement in this process. It was suggested that changes in smooth
      muscle adrenoceptor populations may be an important mechanism by which gut
      inflammation alters intestinal motility.

PMID- 8536164
TI  - Many new jobs--the myth & the reality.

PMID- 8536165
TI  - THE CNA PAC: a vital tool in the restructuring battle.

PMID- 8536166
TI  - Canadian nurse leader speaks of healthcare restructuring.

PMID- 8536167
TI  - Why I will vote to leave ANA.

PMID- 8536168
TI  - Shirley Coleman, RN: through the eyes of a veteran activist. Interview by Rose
      Ann DeMoro.

PMID- 8536169
TI  - ANA weak on protecting nursing practice.

PMID- 8536170
TI  - Why disaffiliate? To focus our resources on protecting our practice and patients.

PMID- 8536171
TI  - International Unity Conference.

PMID- 8536172
TI  - California Nurses Association. Securing our future: creating a plan to defend our
      patients.

PMID- 8536173
TI  - Patient 'perception' centered care.

PMID- 8536174
TI  - Kaise, Curran and the next millennium.

PMID- 8536175
TI  - True professionalism and 'elegant militancy'.

PMID- 8536176
TI  - Kaiser's change of course: anti-union, anti-patient, anti-worker.

PMID- 8536177
TI  - Richard Scott--the empire builder.

PMID- 8536179
TI  - Screening for Growth Towards 2000. Proceedings of a conference. London, United
      Kingdom, 14 December 1994.

PMID- 8536178
TI  - Do general practitioners influence the uptake of breast cancer screening?
AB  - OBJECTIVES: To investigate the relative importance of patient and general
      practice characteristics in explaining variations between practices in the uptake
      of breast cancer screening. DESIGN: Ecological study examining variations in
      breast cancer screening rates among 131 general practices using routine data.
      SETTING: Merton, Sutton, and Wandsworth Family Health Services Authority, which
      covers parts of inner and outer London. MAIN OUTCOME MEASURE: Percentage of
      eligible women aged 50-64 who attended for mammography during the first round of
      screening for breast cancer (1991-1994). RESULTS: Of the 43,063 women eligible
      for breast cancer screening, 25,826 (60%) attended for a mammogram. Breast cancer
      screening rates in individual practices varied from 12.5% to 84.5%. The estimated
      percentage list inflation for the practices was the variable most highly
      correlated with screening rates (r = -0.69). There were also strong negative
      correlations between screening rates and variables associated with social
      deprivation, such as the estimated percentage of the practice population living
      in households without a car (r = -0.61), and with variables that measured the
      ethnic make-up of practice populations, such as the estimated percentage of
      people in non-white ethnic groups (r = -0.60). Screening rates were significantly
      higher in practices with a computer than in those without (59.5% v 53.9%,
      difference 5.6%, 95% confidence interval 1.1 to 10.2%). There was no significant
      difference in screening rates between practices with and without a female
      partner; with and without a practice nurse; and with and without a practice
      manager. In a forward stepwise multiple regression model that explained 58% of
      the variation in breast cancer screening rates, four factors were significant
      independent predictors (at P = 0.05) of screening rates: list inflation and
      people living in households without a car were both negative predictors of
      screening rates, and chronic illness and the number of partners in a practice
      were both positive predictors of screening rates. The practice with the highest
      screening rate (84.5%) contacted all women invited for screening to encourage
      them to attend for their mammogram and achieved a rate 38% higher than predicted
      from the regression model. Breast cancer screening rates were on average lower
      than cervical cancer screening rates (mean difference 14.5%, standard deviation
      12.0%) and were less strongly associated with practice characteristics.
      CONCLUSIONS: The strong negative correlation between breast cancer screening
      rates and list inflation shows the importance of accurate age-sex registers in
      achieving high breast cancer screening rates. Breast cancer screening units,
      family health services authorities, and general practitioners need to collaborate
      to improve the accuracy of the age-sex registers used to generate invitations for
      breast cancer screening. The success of the practice with the highest screening
      rate suggests that practices can influence the uptake of breast cancer screening
      among their patients. Giving general practitioners a greater role in breast
      cancer screening, either by offering them financial incentives or by giving them
      clerical support to check prior notification lists and contact nonattenders, may
      also help to increase breast cancer screening rates.

PMID- 8536180
TI  - Epidemiology of short stature due to growth failure.

PMID- 8536181
TI  - Short stature: does it matter? A review of the evidence.
AB  - Short stature is widely regarded to be a liability, but despite the importance
      commonly ascribed to the psychological impact of physique, there is a paucity of
      methodologically sound research on the topic. The question of growth hormone
      therapy for a short, but otherwise normal child is still controversial. The
      justification for such treatment will depend not only on whether a marked
      improvement in height can be achieved but also on whether short stature can be
      shown to be an appreciable handicap, either in childhood or later in life. There
      is some evidence, though much is anecdotal, to suggest that the short statured
      adult is disadvantaged both socially and economically. There are no conclusive
      data as yet, however, to suggest that short statured children, either before or
      during early adolescence have significantly lower scores on conventional
      psychometric testing than children of average stature. Possibly, the problems
      associated with short stature will only emerge in the older adolescent, but for
      the present, alternative, less expensive forms of treatment should be considered
      for those children apparently unable to cope.

PMID- 8536182
TI  - Genetic and environmental influences on growth.
AB  - OBJECTIVES: To provide an overview of the factors associated with growth in
      primary school children in England and Scotland and to provide information about
      the secular trend of growth in the last 20 years. SETTING: Representative English
      and Scottish samples and an English inner city sample. METHODS: The study had a
      mixed longitudinal design from 1972 to 1994. Between 8000 and 10,000 children
      participated in each survey. Height was measured in at least 95% of the children
      in most surveys, and 75% to 85% of parents provided information about family
      background. Main results are based on published information. Multiple regression
      was used for most of the analyses. RESULTS: Parents' height, child's birth
      weight, mother's age at child's delivery, ethnic background and, in white
      children, family size are the only factors markedly associated with height.
      Variables that have traditionally been used to assess the possible effect of
      social conditions were generally not associated with height. The height increase
      was more marked in Scotland than England over the period 1972 to 1990, and the
      differences in height of children in the two countries is now minimal.
      CONCLUSIONS: Most factors cannot be neatly classified as purely genetic or
      environmental, but seem to indicate that genes are relatively more important.
      Social factors usually assessed in growth studies do not have an important effect
      on growth. The marked increase of height over time indicates that the environment
      and social conditions have allowed children to grow taller. Sibship size is the
      only factor that was shown to be related to the secular trend in growth.

PMID- 8536183
TI  - Growth screening and urban deprivation.
AB  - OBJECTIVES: To assess the effect of urban deprivation on childhood growth in a
      modern British society by analysing data from a regional growth survey, the
      Tayside growth study. SETTING: The Tayside Region in Scotland, which has three
      districts with distinct socioeconomic status: Dundee (D, urban city), Angus (A,
      rural), and Perth (P, rural and county town). SUBJECTS AND METHODS: Height and
      weight of 23,046 children (> 90% of the regional childhood population) were
      measured as part of a child health surveillance programme, by community health
      care workers at 3, 5, 7, 9, 11, and 14 years. Height standard deviation score
      (calculated against Tanner) and body mass index (BMI-weight (kg)/height (m)2)
      were calculated for each child by a central computer program; mean height
      standard deviation score and BMI standard deviation score were calculated for
      each measuring centre (school, health clinic). A deprivation score for each
      centre was calculated from the prevalence of single parent families; families
      with more than three children; unemployment rate; the number of social class V
      individuals; the percentage of council houses. RESULTS: Mean height standard
      deviation score for Tayside was 0.11. An intraregional difference was
      demonstrated: mean height standard deviation score (SD) D = 0.04 (1.0); A = 0.14
      (1.1); P = 0.21 (1.1); P < 0.002. There was a positive association between short
      stature and increasing social deprivation seen throughout Tayside (P < 0.05),
      with a strong association in Dundee primary school children (r = 0.6; P < 0.001).
      Analysis by district showed that the association was significant only above the
      age of 8 (P < 0.004). There was no relation between BMI and social deprivation.
      CONCLUSIONS: In an industrialised developed society, urban deprivation appears to
      influence height mostly in late childhood, and this association should be taken
      into consideration in the clinical management of short stature. Height seems to
      be a better physical indicator of urban deprivation, and hence an index of
      childhood health, than BMI.

PMID- 8536184
TI  - Failure to thrive and the risk of child abuse: a prospective population survey.
AB  - OBJECTIVE: To identify the relative importance of failure to thrive during
      infancy as a risk factor for later abuse or neglect. DESIGN: Whole population
      birth cohort (1 January to 31 December 1986) studied prospectively over a four
      year period. SETTING: An inner city health district in London, England. SUBJECTS:
      2609 births, of whom 47 were identified as having non-organic failure to thrive
      by first birthday. MAIN OUTCOME MEASURES: Registration on Child Protection
      Register, or subject to investigation of suspected abuse or neglect without
      registration. RESULTS: 2.5% (64) of birth cohort had been placed on the Child
      Protection Register during the period 1986-1990, and a further 1.2% (32) had been
      a cause for concern. The relative risk attributable to non-organic failure to
      thrive was 4.3 (95% CI 1.65 to 11.94) and exceeded other measured risk factors,
      including birth weight < 2500 g, 1.96 (95% CI 1.01 to 3.82); gestation < 35
      weeks, 3.26 (95% CI 1.32 to 3.75); ordinal position > or = 4, 1.53 (95% CI 0.72
      to 3.23). A multiple logistic regression confirmed the independent contribution
      of non-organic failure to thrive to subsequent poor parenting warranting
      professional intervention. CONCLUSIONS: Early postnatal non-organic failure to
      thrive is a risk factor for later serious parenting deficiencies, but previous
      research has overstated its importance. Within the community studied the nature
      of subsequent risk was (non-nutritional) neglect, rather than non-accidental
      injury. More than eight out of 10 cases do not give further cause for concern.

PMID- 8536185
TI  - Common causes of short stature detectable by a height surveillance programme.

PMID- 8536186
TI  - United Kingdom community growth screening 1994: a survey of current practice.
      "Screening for Growth Towards 2000" Scientific Organising Committee.
AB  - OBJECTIVE: To determine current policies, resources, and attitudes to community
      growth screening in the United Kingdom. METHODS: A postal survey of community
      paediatricians and paediatric endocrinologists. RESULTS: 164 replies were
      received-most from senior clinical medical officers or community paediatricians
      covering between 68 and 78% of the United Kingdom population. One hundred and
      thirty three (81%) trusts or districts had a written growth policy. Preschool and
      school age height screening took place in 75% and 81% of districts respectively,
      but most children were only measured once before school or at school. Policies
      for the age at which measurements were made and their frequency varied
      enormously. Seventy three per cent used standard equipment, the most popular
      being the Minimetre. A wide variety of charts were used, of which 23% were
      decimal age charts. A large number of referral criteria were used, including
      height, height velocity, and weight. Most children were referred to hospital
      outpatient clinics rather than specialist growth clinics. CONCLUSIONS: Over 90%
      of respondents felt that growth screening was either extremely valuable or useful
      depending on resources. The survey showed a widespread lack of standardisation of
      equipment, charts, and policies. Referral criteria and objectives need to be
      clarified by research and audit, and growth monitoring integrated into a
      systematic programme of child health surveillance.

PMID- 8536187
TI  - Setting up a height surveillance programme: recommendations based on the Hackney
      growth initiative.

PMID- 8536188
TI  - The Oxford growth study: a district growth surveillance programme 1988-1994.
AB  - OBJECTIVES: To develop a method of community based growth assessment. SETTING:
      Oxford District, United Kingdom. METHODS: A system of growth surveillance
      involving a community consultant paediatrician, a paediatric endocrinologist, a
      clinical auxologist, a project coordinator, and the many primary health care
      teams was started. Letters and meetings were arranged to introduce the programme
      to general practitioners and health visitors, emphasising the importance of
      growth assessment in normal child development. They were asked to measure all
      children as part of their routine developmental checks at 3 and 4.5 years of age.
      Community growth assessment clinics staffed by an experienced auxologist were
      established. Children whose heights were more than two standard deviation (SD)
      scores below the mean or whose height SD score decreased between the two ages
      were referred to the clinic. Any child whose height was more than 3 SD scores
      below the mean was referred directly to the paediatric endocrinologist. Those
      seen in the community clinics were followed up for a year and if their velocity
      was > 25th centile, karyotype normal, and bone age appropriately delayed, they
      were discharged to the general practitioner for further follow up. Any child with
      an annual velocity < 25th centile was referred to the endocrinologist. RESULTS:
      Of 20,338 children monitored, 260 (1.3%) had heights > -2 SD scores. Seventy six
      were lost to follow up, 35 were measuring errors, 69 were already seeing a
      paediatrician, leaving 80 children to be evaluated. Of these, 69 were "short
      normals" and 11 were newly identified diagnoses. CONCLUSIONS: This system of
      secondary referral keeps normal healthy children out of hospital, avoids
      unnecessary over-investigation, reduces travel and anxiety for families, avoids
      filling specialist clinics with normal children, and provides an inexpensive
      system of growth surveillance.

PMID- 8536189
TI  - Can we measure growth?
AB  - Poor installation and maintenance of height measuring equipment is a serious
      problem in the community. With care, however, height can be measured with
      sufficient precision (+/- 0.5 cm) to identify unusually short or tall stature.
      Height velocity, on the other hand, is liable to misinterpretation. It cannot be
      estimated with sufficient precision to identify abnormal growth in the short
      term. There is no correlation between two successive 12 month velocities. When a
      trend towards poor velocity is beyond all doubt then it will be apparent on the
      height chart alone. In addition, "poor" or "excessive" growth is conditional on
      the height of the child: short children do not grow at the same rate as tall. A
      diagnosis of abnormal growth requires long term monitoring and is best seen as a
      series of height measurements crossing the centiles on the height chart. Given
      the correct equipment and training, height or length can be measured with a fair
      degree of precision in the youngest of children. The earlier measurements begin,
      the sooner an abnormal pattern of growth will become evident. The regular
      monitoring of height should be standard practice and available to each and every
      child.

PMID- 8536190
TI  - Referral criteria for growth screening.
AB  - Population height screening studies performed over the past 20 years have shown
      that between 17 and 21% of children with heights below the third centile have
      organic disease, of whom about 20% will be new diagnoses. The likelihood of
      organic disease increases to 50% for children with heights below -3 SDs. The age
      of screening will also influence the outcome as both acquired disease and
      disorders with progressive growth slowing, such as Turner's syndrome, are more
      likely to be detected by screening at an older age. Height velocity as a
      screening tool has evoked interest for many years as, despite technical problems,
      slowly growing children are thought more likely to have disease. Inclusion of
      height or height/weight relations may further improve screening sensitivity. It
      may assist in the early detection of coeliac disease or eating disorders in older
      children. A minimum of three measurements is required to define an individual's
      growth pattern and, preferably, five or six measurements spread over the
      preschool and primary school years. The value of extension of growth screening to
      the secondary school age group remains uncertain. Children should be screened for
      both height and weight and referred when there are major discrepancies between
      these two measurements (more than three centile bands). A two level system of
      referral with a community assessment for some children and a direct referral to a
      growth clinic for children with more severe growth disturbance may be the best
      use of resources.

PMID- 8536191
TI  - An international perspective on height surveillance.

PMID- 8536192
TI  - Growth monitoring: the next five years.

PMID- 8536193
TI  - Diagnostic tests.

PMID- 8536195
TI  - Managing managed care.

PMID- 8536194
TI  - Toluidine Blue.

PMID- 8536196
TI  - Dental internships in Canada.

PMID- 8536197
TI  - Le Fort 1 downfracture approach for the treatment of a posterior maxillary
      ameloblastoma.
AB  - The ameloblastoma is a slow-growing insidious tumor derived from the dental
      lamina. It may be described as locally invasive and clinically persistent, and it
      has high recurrence rates if adequate treatment is not rendered. From a clinical
      perspective, the maxillary ameloblastoma is considered to be more aggressive than
      its mandibular counterpart. This is because the maxillary bone is thin and more
      easily penetrated, and not because of a difference in biological behavior. In the
      treatment of intraosseous multicystic or solid maxillary ameloblastomas, many
      authors stress the need for adequate access to achieve a proper surgical
      resection. This paper presents a case of maxillary ameloblastoma that was treated
      using a Le Fort 1 downfracture technique in combination with a segmental
      resection of the posterior part of the left maxilla. The Le Fort 1 technique
      provided excellent access and visibility, especially on the medial aspect of the
      resection. No major problems were encountered with the technique. Six months
      after the resection, the patient remained clinically and radiographically free of
      the tumor. The need for long-term follow-up is stressed.

PMID- 8536198
TI  - Tori mandibularis: a case report and review of the literature.
AB  - Many dentists have patients in their practice with mandibular exostoses, termed
      torus mandibularis. The majority of these asymptomatic, benign bony outgrowths
      remain undisturbed over the patient's lifetime. However, the tori occasionally
      need to be removed. The differential diagnosis for the tori are discussed as well
      as the indications and techniques for their removal. Various hypotheses
      concerning the etiology and epidemiology of torus mandibularis are also reviewed.

PMID- 8536199
TI  - [Arteriovenous malformations, a diagnostic responsibility of the dentist].

PMID- 8536200
TI  - Intra-articular calcaneal fractures. Current concepts.
AB  - Intra-articular fractures of the calcaneus should be treated like any other
      fractures of major weight-bearing joints. Technology has advanced significantly
      in the evaluation of such complex pathology. Surgical instrumentation is now
      available to address any fracture classification. In the past, this had been a
      problem, as maintenance of the anatomic reduction, rigid internal/dynamic
      external fixation, and early mobilization may not have been attainable. The two
      remaining major variables are the mechanism of injury and its force that creates
      the fracture in combination with a very complex intra-articular anatomical
      structure. There will always be some morbidity in complex and serious fractures,
      but at least a more favorable outcome may be attainable with application of the
      current concepts discussed in this text. Finally, the most crucial factor when
      dealing with this trauma is the skill of the surgeon, which includes his or her
      decision-making, preoperative planning, surgical acumen, atraumatic technique,
      experience, and training and postoperative management of possible complications.

PMID- 8536201
TI  - Lisfranc's fracture-dislocation. A literature review and case presentations of
      tarsometatarsal joint injuries.
AB  - Lisfranc's fracture-dislocations are relatively infrequent injuries that may
      result in major debilitation. A review of the literature is presented with focus
      on the proper evaluation, diagnosis, and management of these injuries. Three
      cases are presented that illustrate the more common mechanisms of injury.

PMID- 8536202
TI  - The internal fixation of ankle fracture repair.
AB  - A descriptive overview of the type of internal fixation, the biomechanical
      principles of this fixation technique, and the methods of application are
      outlined. Clinical illustrations demonstrate some of the more commonly used
      internal fixation techniques.

PMID- 8536203
TI  - Diagnosis and treatment of Achilles tendon rupture.
AB  - Achilles tendon ruptures are challenging injuries. The author's intraoperative
      classification and concomitant reconstructive procedures serve as guidelines for
      surgeons. The goals of surgical repair are outlined.

PMID- 8536204
TI  - Current concepts in the diagnosis and treatment of ankle sprains.
AB  - Simple ankle sprains are common injuries. Failure to evaluate, diagnose, and
      adequately treat severe ankle sprains results in continued pain, instability, and
      decreased function. This article reviews the examination, stabilization
      procedures, physical therapy techniques, and complications of these injuries.

PMID- 8536205
TI  - Transchondral fractures of the talar dome.
AB  - The authors thoroughly review transchondral fractures of the talar dome. The
      causes, presentation, diagnosis, and treatments are discussed in detail. In
      addition, a study of 85 patients with chronic ankle pain is presented.

PMID- 8536206
TI  - Gunshot wounds to the foot and ankle.
AB  - Gunshot wounds to the foot and ankle can be a devastating injury. This article
      discusses the basic physics of ballistics and its unique role in open fracture
      treatment. Classification and treatment protocol are also discussed.

PMID- 8536207
TI  - Tibialis posterior tendon dysfunction and peroneal tendon subluxation.
AB  - The authors overview tibialis posterior dysfunction (TPD) with emphasis on a
      criteria-oriented surgical protocol for management of the various clinical and
      pathologic stages of TPD. Subluxation of the peroneal tendons is also detailed
      with respect to diagnosis and treatment.

PMID- 8536208
TI  - Fifth metatarsal fractures. Biomechanics, classification, and treatment.
AB  - Fractures of the fifth metatarsal are treated conceptually based on anatomic
      location and character of the fracture site. Intra-articular disruptions require
      reconstruction, if possible. Malalignment of acute fractures requires either
      closed reduction or open reduction if the malalignment represents a load-bearing
      dysfunction to the forefoot. Segmental defects require bone grafting and
      stabilization with plate and screws. Jones fracture is most effectively managed
      with medullary lag screw delivery in the active or athletic patient. Casting can
      be considered for high-risk patients. Late bone grafting for sclerotic nonunion
      is necessary with inlaid grafts harvested from the calcaneus or tibia. Tuberosity
      fractures require open reduction only when articular involvement is a problem or
      when distraction is apparent. Otherwise, they can be expected to heal rapidly
      without long-term problems.

PMID- 8536209
TI  - First metatarsal fractures.
AB  - First metatarsal fractures are rare because of their thick size and shape. They
      are to be treated aggressively because of the prolonged disability associated
      with such fractures. Any injury to the first ray may drastically alter the
      pattern of normal gait and weight-bearing. Most of the literature regarding such
      fractures is anecdotal, and there is little in the way of scientific articles
      that investigate their management. The general consensus for treatment of closed,
      nondisplaced first metatarsal fractures is to use some form of plaster
      immobilization. Nevertheless, there is much variation in the literature
      concerning the length of time patients should be casted. Rigid internal fixation
      using AO techniques is preferred if open reduction is to be instituted. Long-term
      complications with first metatarsal fractures are attributed mostly to malunion
      in the sagittal plane, resulting in a nonplantigrade foot.

PMID- 8536210
TI  - Fractures of the central metatarsals.
AB  - Central metatarsal fractures are unique, secondary to biomechanical function,
      anatomy, and position within the foot. This article reviews the current and
      historical literature and the classic textbooks on fracture management to give a
      thorough understanding of the anatomy, biomechanics, incidence, mechanism of
      injury, classification, diagnosis, and treatment of the various presentations of
      this type of fracture.

PMID- 8536211
TI  - Midfoot fractures.
AB  - Midfoot fractures, which include injuries to the tarsal navicular, cunieforms,
      and the cuboid, are uncommonly detected. Prompt diagnosis and appropriate
      treatment of these fractures are essential for maintaining normal foot
      biomechanical function. This article reviews various midfoot fractures.

PMID- 8536212
TI  - Treatment of open fractures.
AB  - This article reviews current concepts in treating open fractures along with case
      studies to illustrate specific treatment procedures. It should be used as a basis
      for care and provide the fundamentals to successfully treat patients in a trauma
      setting. The practitioner will find this a challenging and exciting area for
      professional practice.

PMID- 8536213
TI  - Fracture blisters.
AB  - Fracture blisters can pose a problem when dealing with trauma. The potential to
      increase the complication rate, delay surgery, and prolong wound healing are
      possible sequelae. Edema has to be controlled, however, because the blisters can
      form in spite of ice, elevation, and compression. They may also appear even after
      prompt ORIF. High-energy trauma predisposes one to develop fracture blisters.
      Blisters can be discovered even after closed reduction and at a subsequent cast
      change. As with all pathologic conditions, the index of suspicion has to be high
      (Fig. 7).

PMID- 8536214
TI  - Glycosyltransferase activities in human meningiomas. Preliminary results.
AB  - The biosynthesis of a given glycosphingolipid is under the control of specific
      glycosyltransferases, while its catabolism is catalyzed by step-wise action of
      glycosidases. The net amount of glycolipids apparently result from the difference
      between these two processes. However, other parameters should be taken into
      consideration, such as intracellular recycling of catabolic products, membrane
      insertion, and membrane turnover. In order to establish a possible correlation
      between ganglioside expression in brain tumor and the activities of the enzymes
      involved in their metabolism, we analyzed the activities of specific
      sialyltransferases (SAT-1 and SAT-2), galactosyltransferase (GalT-4), N
      acetylgalactosaminyltransferase (GalNAcT-1), and N-acetylglucosaminyltransferase
      (GlcNAcT-1) in 9 human meningiomas whose ganglioside pattern was characterized
      either by the predominance ganglioside GM3 (4 out of 9) or ganglioside GD3 (5 out
      of 9). The results indicated a strong correlation between the GM3/GD3 ratio and
      SAT-2 activity; to the contrary, SAT-1 activity did not show any correlation if
      compared with the Lc2/GM3 ratio. In all the samples where GM3 was the main
      ganglioside, little or no activity of GalNAcT-1 and GlcNAcT-1 was detectable.

PMID- 8536215
TI  - Growth inhibitory action of brefeldin A with taxol and tiazofurin in human breast
      carcinoma cells.
AB  - Brefeldin A (NSC 89671), a macrocyclic lactone, blocks cellular protein transport
      by disturbing the association and dissociation of the Golgi apparatus with a 110
      kD protein which is regulated by GTP. Brefeldin also induces retrograde transport
      from the Golgi membrane to the endoplasmic reticulum, which is mediated by
      microtubules which also require GTP for their biosynthesis. The anti-cancer
      action of taxol is exerted by enhancing tubulin polymerization in microtubule
      assembly; tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 28693)
      acts through decreasing cellular GTP concentrations. Therefore, we tested the
      hypothesis that taxol (paclitaxel, NSC 125975) or tiazofurin might provide
      synergism with brefeldin. In human breast carcinoma MDA-MB-435 cells in the
      growth inhibition assays for brefeldin, taxol and tiazofurin, the IC50s were 41
      nM, 6 nM and 13 microM, respectively. When brefeldin and taxol were given
      simultaneously, addition (brefeldin 10 nM with taxol 2 to 8 nM) or synergism
      (brefeldin 30 nM with taxol 2 to 8 nM) was observed. When brefeldin and
      tiazofurin were given simultaneously, or tiazofurin was followed 12 h later by
      brefeldin, addition was observed. The protocols yielding synergism and addition
      should be of value in the design of clinical trials for breast carcinoma.

PMID- 8536216
TI  - Erythrocytes from Yoshida ascites sarcoma-bearing rats have reduced surface
      charge: the effect of tumor products.
AB  - Erythrocytes from the circulation of rats bearing intraperitoneal Yoshida ascites
      sarcoma, as well as the red cells contaminating the tumor fluid, exhibit higher
      concanavalin A (Con A)-mediated agglutination than the cells from normal animals.
      Two proteins have been purified earlier from the ascites fluid that can impart
      high agglutinability on the cells in vitro. We report here that the erythrocytes
      from the tumor-bearing rats exhibit reduced electrophoretic mobility compared to
      the cells from normal animals (P < 0.001), which correlates with the increase in
      their Con A-agglutinability (r = 0.998). The two purified proteins also cause
      reduction in the electrophoretic mobility of erythrocytes (P < 0.01). Thus the
      modification of the host cell surface observed in tumor-bearing rats arises due
      to non-specific binding of tumor products that reduce the host cell surface
      charge.

PMID- 8536217
TI  - Disposition of the plasmacytomagenic alkane pristane (2,6,10,14
      tetramethylpentadecane) in mice.
AB  - The intraperitoneal administration of pristane (2,6,10,14-tetramethylpentadecane)
      induces peritoneal plasmacytomas in genetically susceptible BALB/c mice. The
      purpose of this study was to estimate the disposition of an amount of
      intraperitoneally injected pristane that would conventionally be used in a tumor
      induction protocol. The distribution of 3H-labeled pristane in various tissues
      was monitored by liquid scintillation counting at different times after
      injection. The data show that pristane is present in the blood and detectable in
      all tested tissues during an observation period of one to 64 days. The levels of
      pristane fluctuate in some tissues such as lymph node and bone marrow but show a
      clear tendency to accumulate in others such as liver, spleen and kidney. Evidence
      is also presented for the in vivo metabolism of pristane based on the observed
      urinary excretion of tritium and on the high levels of radioactivity in the gall
      bladder fluid. It is concluded that intraperitoneally administered pristane is
      distributed throughout the mouse and is stored in tissues in sufficient amounts
      to allow interactions with the cells residing there.

PMID- 8536218
TI  - Plasma fibronectin and sialic acid levels in various types of human brain tumors.
AB  - In this study, fibronectin and sialic acid concentrations were determined in
      plasma from patients with pituitary adenoma, meningioma and glioma, and, from
      controls. The mean plasma fibronectin levels in patients with pituitary adenoma,
      meningioma and glioma (p < 0.001) appeared to be significantly lower than
      controls. On the contrary, the mean plasma sialic acid values in patients with
      pituitary adenoma (p < 0.01), and glioma (p < 0.001) were significantly higher as
      compared to normal plasmas. The mean plasma sialic acid values in patients with
      meningioma were not different from those in controls. Also, the mean fibronectin
      levels in patients with glioma were found to be significantly higher than those
      in patients with meningioma (p < 0.05).

PMID- 8536219
TI  - Effect of selenium on lipids and some lipid metabolising enzymes in DMBA induced
      mammary tumor rats.
AB  - Current evidences clearly point out that an increase in lipid peroxidation
      influences lipid metabolism in cancer patients. Several investigations recognize
      selenium as a potent antioxidant, as well as an anticarcinogen, in both animal
      and human systems. Selenium was administered to Wistar rats bearing mammary tumor
      induced by 7,12-dimethylbenz(a)anthracene (DMBA) to study alterations in the
      concentration of lipid profiles and in the activities of some lipid metabolising
      enzymes. Control and tumor-bearing rats administered with selenium, were fed 5 mg
      sodium selenite/kg diet from the day of tumor induction. Plasma total lipids,
      total cholesterol, free fatty acids, triglycerides, phospholipids, VLDL and LDL
      cholesterol were significantly lower in selenium-treated rats bearing tumors,
      whereas, plasma ester cholesterol and HDL cholesterol were significantly greater
      due to selenium administration in DMBA induced-tumor rats. Total lipase and
      lecithin: cholesterol acyltransferase registered greater activities in plasma of
      selenium administered rats with tumor, while the activity of preheparin
      lipoprotein lipases in plasma of rats bearing tumors was lower due to selenium
      administration. These observations clearly indicate the effect of selenium in
      correcting the abnormalities of lipid metabolism in tumor-induced rats.

PMID- 8536220
TI  - Seventeenth Annual Interdisciplinary Cancer Research Workshop.
AB  - The Seventeenth Annual Interdisciplinary Cancer Research Workshop was held at the
      University of New Orleans on March 4, 1994. It was again sponsored by the Cancer
      Association of Greater New Orleans, a United Way Agency. As all the previous
      workshops in this highly successful series, it was organized by Peter Politzer
      (University of New Orleans), with the assistance of Anita H. Buckel (University
      of New Orleans) and James R. Jeter (Tulane University School of Medicine, New
      Orleans). The three invited speakers were Robert J. Coffey (Vanderbilt
      University, Nashville, TN), Suzanne A. W. Fuqua (University of Texas Health
      Science Center, San Antonio, TX), and Frank M. Torti (Bowman Gray School of
      Medicine, Wake Forest University, Winston-Salem, NC). A one-hour-discussion
      period in the afternoon presented ample opportunity for an exchange of ideas and
      research findings among the speakers and the workshop participants. James R.
      Jeter served as the moderator of this lively discussion session.

PMID- 8536221
TI  - Mitochondrial and cytosolic rhodanese from liver of DAB treated mice. II. Some
      properties and spectral studies.
AB  - Rhodanese (thiosulfate: cyanide sulfurtransferase) shows distinctive
      mitochondrial and cytoplasmic activities in several models of tumorigenesis. To
      investigate the basis for these differences, the enzyme was purified from the
      mitochondrial and cytosolic liver fractions of mice treated with the carcinogen p
      dimethyl-aminoazobenzene (DAB) and some properties were studied. Mitochondrial
      and cytoplasmic rhodanese exhibited different responses to the effect of ionic
      strength, denaturants, sulphydryl reagents, lipids and detergents, but no
      significant difference between enzymes purified from controls or DAB treated
      animals was observed. It is important to note that although chemical studies did
      not show very striking differences between either of the rhodanese forms,
      fluorescence spectral studies suggested that in DAB-treated mice, the cytosolic
      rhodanese would be present almost completely as the sulfur-free form, while the
      mitochondrial enzyme would be present as the sulfur-substituted form. These
      findings would justify the high rhodanese activity present in mitochondria. On
      the other hand, in control animals, rhodanese would exist only as the partial
      sulfur-substituted form in both fractions.

PMID- 8536222
TI  - Further evidence for the lack of correlation between the breakpoint site within M
      BCR and CML prognosis and for the occasional involvement of p53 in
      transformation.
AB  - The actual significance of the type of BCR-ABL rearrangement in chronic myeloid
      leukemia (CML) prognosis remains controversial. Also, the molecular events that
      lead to CML progression are largely unknown. We analyzed the M-BCR breakpoint
      position in 64 CML patients by Southern blot and correlated the molecular
      findings with the cytogenetic, hematologic, and clinical data. No statistically
      significant differences were found with respect to the clinical and hematologic
      data presented at diagnosis or in the median duration of chronic phase (CP) and
      survival between the groups of patients with 5' and 3' breakpoints. We also
      studied by PCR-SSCP and direct sequencing the p53 gene in patients with specimens
      available in both chronic phase and blast crisis. We identified p53 mutations in
      17% of the blast crisis samples analyzed, whereas no abnormalities were found in
      CP. This finding suggests that only in a minor fraction of cases are lesions in
      the p53 gene involved in transformation. Given the present findings, along with
      previous reports, we believe that a novel mechanism to explain the heterogeneity
      of CML should be postulated and actively pursued, as should the identification of
      secondary molecular events more consistently involved in progression.

PMID- 8536223
TI  - Cytogenetic findings in a case of congenital mesoblastic nephroma.
AB  - Congenital mesoblastic nephroma (CMN) is a benign, but locally aggressive, renal
      tumor of early infancy. Few metastases have been reported, but local recurrence
      is well documented. CMN is histologically distinct from Wilms' tumor and other
      childhood renal tumors, and is typically treated by surgical excision without
      adjuvant therapy. Cytogenetic abnormalities in these tumors have been described
      and are often compared with abnormalities seen in leiomyomas, fibromatoses, and
      infantile fibrosarcomas. In particular, trisomy 11 has been suggested as a
      nonrandom occurrence in CMNs. We describe a case of CMN in a 4-month-old female
      infant. The diagnostic histologic features included a monophasic mesenchymal
      appearance, prominent staghorn vascular spaces, and extensive infiltration of the
      adjacent kidney. Cytogenetic analysis showed a hyperdiploid chromosome number and
      a single structural abnormality involving a translocation between chromosomes 12
      and 15. The composite karyotypic interpretation was: 46-47,XX,-X, +8,
      +11,t(12;15)(p12;q25), +17, +20[cp14]. The significance of karyotypic changes in
      this tumor is currently unknown. A genetic basis for histologic variability and
      progression may exist if certain cytogenetic abnormalities, such as trisomy 11 or
      specific translocations, confer a proliferative advantage. Additional cases are
      required to correlate cytogenetic findings with the biologic behaviors of CMN. We
      present this case as a contribution to existing literature describing these
      relatively rare and interesting renal tumors.

PMID- 8536224
TI  - FISH in the evaluation of pleural and ascitic fluids.
AB  - Pleural and ascitic fluids (PAF) are complications of both nonmalignant and
      malignant conditions, such as congestive heart failure and chronic infections, as
      well as neoplasias, such as mesothelioma, lymphoma, and adenocarcinomas of the
      lung, ovary, endometrium, breast, colon, stomach, and pancreas. Differentiation
      between malignant and nonmalignant PAF is not always easy to assess on the basis
      of clinical, cytologic, and other criteria. A review of the chromosomal anomalies
      in neoplasms which can cause PAF revealed aneusomies of chromosomes 1, 3, 7, 8,
      10, and 11 in about 40% to 80% of these malignancies. We performed FISH using
      centromere-specific probes for chromosomes 1, 3, 7, 8, 10, and 11 and chromosomal
      analysis on PAF cells from 21 patients, including 3 with ovarian cancer, 2 with
      lymphoma, 5 with adenocarcinoma of unknown origin, 1 with breast cancer, and 10
      with atypical lymphocytosis of unknown cause. The results indicate a) a high
      correspondence between FISH and the clinical diagnosis (9 of the 11 cases of
      malignant fluid showing FISH abnormalities); b) that FISH is more sensitive than
      cytogenetics in detecting abnormal clones (10 vs. 6); and c) that FISH is a
      valuable adjunct to cytology in the interpretation of atypical lymphocytosis (3
      of the 10 cases were shown to be abnormal by FISH). Thus, the FISH technique can
      be a very useful adjunct to conventional cytogenetics in yielding crucial
      information on the origin of PAF.

PMID- 8536225
TI  - A new case of trisomy 5 as sole cytogenetic anomaly in acute myeloid leukemia.
AB  - We present a case of acute myeloid leukemia (AML-M2) with trisomy 5 (+5) as the
      sole cytogenetic abnormality in a woman previously diagnosed with schizophrenia.
      To date, only two cases of AML (other than M2) with +5 as the only change have
      been reported. Moreover, an association between schizophrenia and partial trisomy
      of chromosome 5p has been described recently. To our knowledge, this is the first
      report of AML (subtype-M2) with +5. Noteworthy is the association with
      schizophrenia.

PMID- 8536226
TI  - Cytogenetic characterization of a familial papillary renal cell carcinoma.
AB  - We describe the first case of a familial renal cell carcinoma cytogenetically
      characterized as a papillary renal cell carcinoma. Cytogenetic and molecular
      studies were performed on primary renal cell carcinomas and normal kidney tissue
      from two members of the same family. Both patients showed a normal constitutional
      karyotype. The two tumors analyzed from the first patient showed the numerical
      chromosome alterations characteristic of papillary renal cell carcinomas. From
      the four tumors analyzed in the second patient, three of them presented the
      cytogenetic pattern of papillary renal cell tumors, and the fourth showed only
      structural chromosome abnormalities with the presence of a del(7)t(7;7) or dup(7)
      in all metaphases analyzed. Chromosome 3 was cytogenetically unaffected in all
      tumors from both patients, and restriction fragment length polymorphism analysis
      performed with probe pEFD145 (3p21.1-p23) did not detect any loss of
      heterozygosity.

PMID- 8536227
TI  - The 6th International Workshop on Chromosomes in Solid Tumors. Tucson, Arizona,
      February 19-21, 1995. Abstracts.

PMID- 8536228
TI  - Reverse transcription polymerase chain reaction for the diagnosis and molecular
      monitoring of the PML/RAR alpha fusion gene in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17)
      translocation and a high rate of response to all-trans retinoic acid. The
      translocation generates a PML/RAR alpha chimeric gene which is transcribed in a
      fusion PML/RAR alpha mRNA. In this study, by using RT-PCR, we examined 14 APL
      patients for PML/RAR alpha fusion gene transcripts. Eight patients were studied
      at diagnosis, 2 at relapse, 1 both at relapse and after reinduction, 1 both at
      diagnosis and after three cycles of consolidation chemotherapy, and 2 patients
      were examined for minimal residual disease (MRD) 4 months after completing
      treatment. A positive result was observed in all 14 cases. Two patients who were
      in complete hematologic remission had evidence of hematologic relapse soon after
      the positive test. We conclude that RT-PCR for APL yields important diagnostic
      and prognostic information for the APL patients.

PMID- 8536229
TI  - Carcinoid in a horseshoe kidney. Morphology, immunohistochemistry, and
      cytogenetics.
AB  - Renal carcinoids are very rare neoplasms. We were able to culture and
      subsequently karyotype a carcinoid located in the isthmus of a horseshoe kidney,
      which revealed the following chromosomal pattern: 47,XX, +
      13[8]/46,XX,t(13;14)(q31;q11.2)[5]/46,XX[2]. The DNA index was 1. Our results,
      compared with the sparse data from the literature, suggest that carcinoid of the
      kidney has no cytogenetic aberrations in common with carcinoids from other
      anatomical sites reported. On the other hand, numerical and structural
      aberrations of chromosome 13 seem to play a crucial role in the development of
      metanephric-derived renal tumors.

PMID- 8536230
TI  - An abnormal clone with monosomy 7 and trisomy 21 in the bone marrow of a child
      with congenital agranulocytosis (Kostmann disease) treated with granulocyte
      colony-stimulating factor. Evolution towards myelodysplastic syndrome and acute
      basophilic leukemia.
AB  - Cytogenetic analysis of bone marrow cells revealed an abnormal clone with
      monosomy 7 and trisomy 21 in a 12-year-old child with Kostmann disease (KD). The
      patient presented with anemia, thrombocytopenia, and splenomegaly after 5 years
      of treatment with granulocyte colony-stimulating factor (G-CSF). The bone marrow
      morphology was consistent with the diagnosis of myelodysplastic syndrome (MDS).
      Administration of G-CSF was discontinued at this point. Bone marrow studies 2 and
      5 months later showed persistence of both myelodysplasia and the abnormal clone
      with monosomy 7 and trisomy 21. Monosomy 7 was also confirmed by fluorescence in
      situ hybridization (FISH). After 2 months of follow-up, the patient presented
      with acute basophilic leukemia, a very rare variant of acute myeloid leukemia
      (AML), expressing the same bone marrow chromosome abnormalities as observed
      earlier. This is a rare case of KD with prolonged survival and a cytogenetically
      abnormal clone evolving to MDS and acute basophilic leukemia. The significance of
      monosomy 7 and trisomy 21 in KD treated with G-CSF is discussed.

PMID- 8536231
TI  - Hexasomy of chromosome 8 and trisomy of chromosome 11 characterize two
      karyotypically independent clones in a case of acute non-lymphocytic leukemia.
      Conventional cytogenetic and FISH investigation.
AB  - A case of ANLL following a myelodysplastic syndrome, probably resulting from
      occupational exposure to ionizing irradiation, with two cytogenetically unrelated
      clones, hexasomy 8 and trisomy 11, was investigated by conventional cytogenetics
      and FISH. Significant quantitative differences between data obtained by metaphase
      and interphase analysis of the hexasomy 8 clone were observed. A difference in
      the sensitivity to chemotherapy of the two clones was found: while the hexasomy 8
      clone markedly decreased in response to treatment, the trisomy 11 clone remained
      unchanged.

PMID- 8536232
TI  - Cytogenetic study of neoplastic and nonneoplastic cells of the skin.
AB  - We describe the cytogenetic study of six neoplastic and eight nonneoplastic skin
      samples from sun-exposed body sites or sites close to tumors. The cytogenetic
      findings revealed that chromosome rearrangements are common in sun-exposed normal
      skin, similar to the situation in cutaneous tumors, and suggest that such
      karyotypic abnormalities might be indicative of the genetic instability caused by
      specific mutations and resulting from carcinogenic exposure of the tissue.

PMID- 8536233
TI  - Cytogenetic analysis of thyroid tumors after cryopreservation.
AB  - Current cytogenetic evaluation of solid tumors is performed on fresh tissue
      specimens requiring on-call tissue culture facilities. The application of
      cryopreservation to tumor samples prior to cytogenetic analysis allows collection
      of tumors to a desired sample size. We evaluated methods of cryopreservation for
      their effects on growth potential from 11 benign thyroids and one papillary
      thyroid cancer. Mitotic indices and thyroglobulin expression applying
      imunocytology were analyzed. Compared to fresh tumors, the revived tumor samples
      showed unaltered thyroglobulin expression. A statistically significant (p <
      0.004) prolongation to develop mitotic activity occurred in samples received
      after the freezing of dispase digested tissues, but not in samples frozen as
      thinly cut pieces. In addition, the data show that cytogenetic analysis at the
      400-band level can be achieved in cryopreserved thyroid tissues.

PMID- 8536234
TI  - Correlation of loss of heterozygosity with cytogenetic analysis using G-banding
      and fluorescence in situ hybridization in aneuploid cultures from two human
      testicular germ-cell tumors.
AB  - A detailed karyotype analysis using fluorescence in situ hybridization (FISH),
      with 24 chromosome-specific paint probes has been carried out on newly
      established cell lines from two testicular tumors, an i(12p)-positive teratoma,
      and an i(12p)-negative combined seminoma/teratoma. This has been correlated with
      loss of heterozygosity (LOH) and allelic imbalance, using DNA RFLP analysis to
      clarify the genetic changes and to identify any common regions of deletion or
      rearrangement. With G-banding alone, a total of 11 breakpoints were recognized.
      After FISH, the position of seven required revision, and 21 new ones were
      identified. The chromosomes involved most frequently in both tumors were numbers
      1, 12, and 18. Breakpoints in 11q and 16q were also seen in both, and seven or
      more copies of 12p per cell were found in all clones. LOH was found for 18q in
      both tumors, and overall was much more frequent in underrepresented regions (one
      or two copies). On the whole, there was good agreement between the cytogenetic
      and DNA RFLP data; loci showing allelic imbalance generally had an odd number of
      copies of the chromosome region in which they were known to be located. Combined
      data on the chromosome 1 translocations in both tumors suggested that
      rearrangements were more complicated than cytogenetics alone had predicted.

PMID- 8536235
TI  - Single-cell trisomy in hematologic malignancy. Random change or tip of the
      iceberg?
AB  - Finding a clone in the bone marrow of a patient with a hematologic disorder is
      important to confirm the neoplastic nature of the disease and may be indicative
      of prognosis. Since cytogenetic analysis detects only actively dividing clones,
      the presence of a single abnormal cell among 20 cells analyzed raises doubts
      about its clonal nature. Fluorescence in situ hybridization (FISH) enables rapid
      detection of certain chromosomal abnormalities in metaphase and interphase cells,
      thus enabling detection of minor or inactive clones. Seven patients with
      hematologic malignancy each having random cell(s) were investigated thus: at
      diagnosis, with MDS and a cell with +8 (two cases) or +9 (one case) and with AML
      and a cell with +4 (one case), +7 (one case), or two cells with +9, +22/ +10,
      +17, +17 (one case). One patient with ALL in remission had one cell with trisomy
      4. One patient, a male aged 66 years with refractory anemia with ringed
      sideroblasts, was found to have a minor trisomy 8 clone in his diagnostic marrow.
      A follow-up marrow 42 months later showed no trisomy 8 cell among 62 metaphases
      analyzed, and the percentage of trisomic cells using FISH on interphase cells was
      within the control range. This patient has survived for more than 42 months
      requiring no treatment. Single-cell abnormalities in the other six cases proved
      to be random events. Thus it appears that single-cell abnormalities may not be
      clonal or at most indicate the presence of a minor clone well below the level of
      cytogenetic detection. The prognostic significance of such minor clones is at
      present unclear.

PMID- 8536236
TI  - p53 mutation in epithelial ovarian carcinoma and borderline ovarian tumor.
AB  - We have investigated a series of 19 human ovarian carcinomas and 17 borderline
      ovarian tumors to determine the loss of heterozygosity on chromosome 17p and
      possible concurrent p53 mutations. Allelic losses were assessed using restriction
      fragment length polymorphism study, and p53 gene mutations were detected by
      single strand conformation polymorphism analysis and by direct sequencing. In
      addition, we stained the same tumor sections immunohistochemically to detect p53
      protein in tissues. Among 19 ovarian malignant tumor samples tested, we
      identified 17p allelic deletions in 12 (63.2%) of 19 informative cases. The p53
      gene mutation was observed in 7 of 19 (36.8%) malignant ovarian tumors, and it
      was predominantly observed in tumors with allelic loss on 17p (six of seven
      tumors, 85.7%). Although 9 cases of 17 borderline ovarian tumors showed shifted
      bands on single strand conformation polymorphism analysis, only one case was
      proved to have a point mutation in direct sequencing. We also obtained six cases
      (31.6%) of positive immunoreactivity from 19 ovarian cancers and 3 cases (17.6%)
      from 17 borderline ovarian tumors. We conclude that loss or inactivation of tumor
      suppressor gene function by chromosome 17p allelic deletions or p53 mutations are
      important genetic changes in ovarian cancer.

PMID- 8536237
TI  - Malignant trophoblastic neoplasms with different modes of origin.
AB  - The genetic origin of 24 trophoblastic neoplasms was determined using PCR
      polymorphisms. Based on pregnancy history, these tumors included nine postmolar
      trophoblastic tumors, 12 tumors preceded by live birth or abortion, and three
      nongestational tumors. Androgenetic origin was defined in eight post-molar
      trophoblastic tumors, and the remaining one might have arisen from a normal
      fertilization. Six tumors retained genetic features carried by the homozygous
      complete mole. Two tumors showed PCR polymorphism compatible with that of the
      heterozygous complete mole. All 12 tumors in the second class had alleles of both
      paternal and maternal contribution. However, discordance of sex between the
      antecedent pregnancy product and the tumor was recognized in three
      choriocarcinomas. The absence of paternal contribution suggested a
      parthenogenetic origin of three nongestational choriocarcinomas. The findings
      that PCR polymorphisms were either homozygous in certain loci or heterozygous in
      others may mean that the tumor was derived from a germ cell after meiosis I. As a
      result, at least three subtypes with different modes of origin were demonstrated
      in the 24 trophoblastic tumors. These findings underscore the importance of
      precise genetic marker analyses in a large series to clearly identify clinical
      and biologic characteristics of each subset of tumors.

PMID- 8536239
TI  - Rehybridization on metaphases studied previously by FISH. An approach to analyze
      chromosome aberrations.
AB  - A new protocol for fluorescence in situ rehybridization is described. Biotin
      labeled chromosome-specific DNA probes were hybridized onto metaphases which
      previously had been studied by FISH. This method makes it possible to reexamine
      the same metaphase spreads with different DNA probes. It allows for precise
      characterization of cytogenetic translocations and for detection of multiple
      aberrations presented in a karyotype. It is especially useful in cases where a
      limited number of cytogenetic preparations are available.

PMID- 8536238
TI  - Cytogenetic, telomere, and telomerase studies in five surgically managed
      lumbosacral chordomas.
AB  - Lumbosacral chordomas are rare skeletal sarcomas of the spine that originate from
      the remnant notochord. The understanding of this human cancer is limited to
      observations of its clinical behavior and its embryonic link. Thus, we performed
      chromosome and molecular analyses from five surgically harvested chordomas in an
      effort to document genetic and biochemical abnormalities which might aid in
      understanding the tumor biology of this understudied neoplasm. Cytogenetic
      analysis of the five chordomas revealed normal results in four patients and
      random abnormalities in only one tumor cell in the 100 cells studied from the
      fifth patient. A repeat telomeric probe (TTAGGG)50 was hybridized to genomic DNA
      isolated from chordoma cells (and HeLa cells) and digested with HinfI. The tumor
      DNA was paired with leukocyte DNA from age-matched controls and revealed telomere
      elongation in four of the four chordoma patients studied with molecular genetic
      techniques. Conversely, telomere length reduction has been reported during in
      vitro senescence of human fibroblasts, giant cell tumor of bone, colon cancer,
      intracranial tumors, childhood leukemia, Wilms tumor, and in HeLa cells.
      Telomerase activity (telomerase is required to maintain telomere integrity) was
      also determined by visualizing the extension of radioactive telomeric repeats on
      DNA sequencing gels. The telomeric fragments were assembled during incubation of
      the cytoplasmic extract containing telomerase. Telomerase activity was observed
      in HeLa (positive control and commercially available cell line), giant cell tumor
      of bone (positive control tumor cells from living patients), and in chordoma
      cells from one of the two chordoma patients (but to a lesser degree compared with
      HeLa). As expected, the chordoma patients' fibroblasts exhibited no telomerase
      activity.

PMID- 8536240
TI  - Accumulation of chromosomal changes in human glioma progression. A cytogenetic
      study of 50 cases.
AB  - Cytogenetic studies of 50 human gliomas, including three oligodendrogliomas, 16
      grade I-III astrocytomas, and 31 glioblastomas multiforme, were performed using
      the short-term tissue culture method. The most common numerical chromosome
      aberrations were +7, -9, -10, -14, and loss of a sex chromosome. Structural
      changes involved predominantly the following chromosome arms: 1q, 2q, 6q, 7q, 9p,
      14q, 17p, and 18p. Losses of chromosomes 9, 10, and 14, often occurring
      simultaneously and in polyploid clones, were observed almost exclusively in high
      grade gliomas, and appear to constitute important events during glioma
      progression.

PMID- 8536241
TI  - Common clonal chromosome aberrations in cytokine-dependent continuous human T
      lymphocyte cell lines.
AB  - Antigen-mediated T-cell proliferation is a transient phenomenon. Like other
      somatic cells, T lymphocytes generally show replicative senescence in vitro.
      However, we here show that cytokine-dependent continuous (immortal) T-cell lines
      can be established from skin biopsy specimens of inflammatory skin diseases.
      Continuous growth can be obtained by culturing T cells in medium supplemented
      with interleukin-2 and interleukin-4, but without antigen or antigen-presenting
      cells added. Loss of the T-cell antigen receptor complex is observed in some of
      the continuous T-cell lines. Most T-cell lines develop clonal chromosome
      aberrations during continuous growth. Aberrations for chromosomes 1, 2, 8, 16,
      and 18 are most commonly observed.

PMID- 8536242
TI  - Chemical induction of sister chromatid exchange at fragile sites.
AB  - Chromosomal breakage was studied for its correlation to sister chromatid exchange
      (SCE) in cultured peripheral blood lymphocytes from normal individuals following
      treatment with different fragile site- and breakage-inducing chemicals. The
      average SCE per cell was similar for cultures untreated or treated with
      fluorodeoxyuridine (FdU), caffeine, and aphidicolin (APC) (6.5 SCE), but elevated
      with mitomycin C (MMC) (46.5 SCE). About half of the breaks induced with caffeine
      and FdU were at fragile sites, with fewer than 10% accompanied by SCE. Forty
      percent of MMC-induced breaks were at fragile sites, of which 47% had SCE. APC
      induced 68% breaks at fragile sites, of which 44% were associated with SCE.
      Fragile sites induced at > 4% included 3p14, 6q26, 7q22, and 16q23. the 3p14
      fragile site was induced by all chemicals except caffeine. The different
      frequency in induction of fragile sites and their association with SCE by the
      chemicals tested suggest that they are related to different mechanisms of
      induction which may be dependent upon nucleotide content.

PMID- 8536243
TI  - An unusual cytogenetic abnormality involving chromosomes 1 and 7 in a case of
      chronic myelomonocytic leukemia.
AB  - We report a case of chronic myelomonocytic leukemia in which cytogenetic analysis
      revealed a 47,XY, +1, +der(7)del(7)(q32q36)ins(7;1)(q32;p36.3p22) chromosomal
      constitution. This abnormal karyotype, which as a whole is new to any myeloid
      malignancy, points to a possible pathogenetic role for the oncogenes MET and FGR
      on the derivative chromosome 7, and for the CSF1 and JUN genes flanking the
      breakpoint on chromosome 1.

PMID- 8536244
TI  - No statistical association between fragile sites and constitutional chromosome
      breakpoints.
AB  - Ten thousand four hundred ninety-two constitutional breakpoints available from
      the cytogenetic literature were analyzed for their coincidence with known fragile
      sites (FS) at 303-band resolution. In this analysis we have taken into account
      the stochastic connections of some features of chromosome bands with both the
      presence of FS and constitutional breakage. Our results suggest that there is no
      particular association between FS and constitutional chromosome rearrangements.

PMID- 8536246
TI  - Tetrasomy 21 as a sole abnormality in erythroleukemia.
AB  - A 13-year-old girl presented with swelling in the neck, fever, bleeding of the
      gums, and hepatosplenomegaly. Bone marrow morphology was suggestive of
      erythroleukemia (AML-M6). Chromosome analysis of the marrow revealed 48,XX, +21,
      +21 as the sole clonal abnormality.

PMID- 8536245
TI  - Translocation of BCR to chromosome 9 in a Philadelphia-negative chronic myeloid
      leukemia.
AB  - We report the case of a patient having Philadelphia-negative, bcr-abl-positive
      chronic myeloid leukemia. In situ hybridization showed the presence of the bcr
      abl fusion on the chromosome 9 long arm in all mitoses observed. Stability of the
      disease was very difficult to obtain because of serious adverse effects to
      interferon and chemotherapy, mainly grade IV neutropenia, and a blast crisis
      occurred 12 months after diagnosis. Only three other patients with such
      presentation (Philadelphia negative, bcr-abl positive with bcr-abl fusion on the
      chromosome 9 long arm) have been reported, with a poor therapeutic response and
      outcome in two of them. Translocation of BCR to chromosome 9 may therefore have a
      worse prognosis than translocation of ABL to chromosome 22 in Philadelphia
      negative chronic myeloid leukemia.

PMID- 8536247
TI  - Cytogenetic analyses of patients with skin tumors.

PMID- 8536248
TI  - Chronic myelomonocytic leukemia with a novel t(5;18) translocation.

PMID- 8536249
TI  - Travelling on the potential energy surfaces of carbohydrates: comparative
      application of an exhaustive systematic conformational search with an heuristic
      search.
AB  - The calculated ensembles found by a heuristic conformational search algorithm,
      CICADA, for three small carbohydrates, ethyl beta-lactoside, methyl alpha-D
      galactoside, and methyl beta-D-galactoside, are evaluated in terms of their
      ability to reproduce time-averaged optical rotation and NMR data. A unique
      dynamic model for methyl beta-D-galactoside has been obtained by fitting
      experimental NOESY volumes to the theoretical ones elaborated from the CICADA
      ensemble internuclear distances with the model-free formalism. In the case of
      ethyl beta-lactoside, the CICADA ensemble is compared to that of an exhaustive
      systematic grid-search method. The CICADA algorithm proved to be a very efficient
      method to find most of the important minima on even very complex potential energy
      surfaces, and the spectral quality of the CICADA ensemble was found to be of
      equal quality, if not superior, to that of the exhaustive systematic grid-search
      method. The CICADA algorithm has several advantages over other conformational
      search algorithms: (1) It has polynomial dependence of dimensions on computer
      time in contrast to the grid search, which has exponential dependence, (2) the
      conformations found are free of artificial harmonic constraint potentials, (3) it
      passes all barriers amongst families of conformations on conformational
      hypersurface but spends almost all its time in the essential highly populated
      areas, (4) the inherent properties of the algorithm make rigorous minimization
      criteria superfluous and provide good convergence behavior, and (5) as an
      important spin-off, it provides low-energy interconversion pathways that can,
      amongst others, be used for estimating adiabatic rotational barriers.

PMID- 8536250
TI  - Determination of the structure of the exopolysaccharide produced by Lactobacillus
      sake 0-1.
AB  - The exopolysaccharide produced by Lactobacillus sake 0-1 in a semi-defined medium
      was found to have an average molecular mass of 6 x 10(6) Da and a composition of
      D-glucose, L-rhamnose, and sn-glycerol 3-phosphate (3:2:1). The polysaccharide is
      partially O-acetylated. By means of partial acid hydrolysis, O-deacetylation,
      deglycerophosphorylation, methylation analysis, and 1D/2D NMR (1H, 13C, and 31P)
      studies the polysaccharide was shown to be composed of repeating units with the
      following structure: [formula: see text]

PMID- 8536251
TI  - The structure of the exopolysaccharide produced by Lactobacillus helveticus 766.
AB  - The exopolysaccharide produced by Lactobacillus helveticus 766 in skimmed milk
      was found to be composed of D-glucose and D-galactose in a molar ratio of 2:1.
      Linkage analysis and 1D/2D NMR studies (1H and 13C) performed on the native
      polysaccharide, and on oligosaccharides obtained from a partial acid hydrolysate,
      showed the polysaccharide to consist of hexasaccharide repeating units with the
      following structure: [formula: see text]

PMID- 8536252
TI  - Carrageenans from the tetrasporic stages of Gigartina clavifera and Gigartina
      alveata (Gigartinaceae, Rhodophyta).
AB  - Modern chemical and spectroscopic techniques have been used to characterise the
      polysaccharides extracted from the tetrasporic life stages of Gigartina clavifera
      and Gigartina alveata. Both are predominantly xi-carrageenans. About one in six
      of the 3-linked residues in both polysaccharides also have a pyruvate acetal
      group at the 4- and 6-positions. In addition, a similar proportion of the 4
      linked units of each polysaccharide are devoid of sulfate groups, whilst more
      have sulfate esters on both O-2 and O-6. Some of the 3-linked units contain a
      sulfate at the 6-position in addition to that at O-2. The polysaccharide from
      tetrasporophytic G. alveata also contains a small but significant number of 3,6
      anhydrogalactosyl units, most of which are naturally sulfated at the 2-position.

PMID- 8536253
TI  - Structural analysis of cyclamen seed xyloglucan oligosaccharides using cellulase
      digestion and spectroscopic methods.
AB  - Xyloglucan polymers have been isolated from cyclamen seeds and characterized by
      both liquid and CP-MAS 13C NMR spectroscopy. Treatment of the polysaccharides
      with cellulase from Trichoderma viride afforded XG oligomers which have been
      studied with both mass spectrometry and NMR spectroscopy. The repeating unit in
      the intact polymers and the most abundant hydrolysis product correspond to the
      Gal1 Xyl3 Glc4 (XXLG) fragment. However, detection of notable amounts of Xyl3
      Glc4 (XXXG) and Gal2 Xyl3 Glc4 (XLLG) indicates that the galactose distribution
      in xyloglucan from cyclamen is irregular. FAB-MS analysis of a new derivative,
      prepared by forming the glycosamine of m-tetrafluoroethoxy aniline, has led to
      unambiguous sequence information for the XXLG oligomer.

PMID- 8536254
TI  - Isolation and characterization of heparan sulfate from crude porcine intestinal
      mucosal peptidoglycan heparin.
AB  - A method for the preparation of heparan sulfate from peptidoglycan heparin is
      described. The objective of this research was to provide a basis for the
      development and validation of an industrial process to support the preclinical
      development of heparan sulfate and/or heparan sulfate derivatives. In the
      preparation of heparan sulfate, heparin was recovered by alcohol fractionation
      and dermatan sulfate was isolated by selective precipitation. The remaining crude
      heparan sulfate was fractionated by anion-exchange chromatography into five
      subfractions. The biological activities of these subfractions were examined by
      anticoagulant and amidolytic assays. Molecular weight and molecular size were
      determined using capillary viscometry and polyacrylamide gel electrophoresis.
      Charge density and degree of sulfation were determined by cellulose acetate
      electrophoresis and elemental analysis. Oligosaccharide and disaccharide analysis
      relied on enzymatic depolymerization using heparin lyases followed by
      polyacrylamide gel and capillary electrophoresis. 1H NMR analysis provided
      detailed structural information on each subfraction. Crude heparin sulfate and
      its subfractions showed significant differences in physical, structural and
      biological properties.

PMID- 8536255
TI  - Enzymic glycosylation of (+/-)-(3,5/4,6)-3,6-diazido-4,5- dihydroxycyclohexene. A
      way to prepare stereochemically pure and enzyme resistant, basic pseudo
      disaccharides as competitive enzyme inhibitors.
AB  - By beta-D-galactosylation of (+/-)-(3,5/4,6)-3,6-diazido-4,5
      dihydroxycyclohexene, pure (+)-3,5/4,6)-3,6-diazido-4-O-(beta-D-galactopyranosyl)
      5-hydrox ycyclohexene (3) was obtained. The diamine (+)-(1,3/2,6)-3,6-diamino-1-O
      (beta-D-galactopyranosyl)-2-hydroxycycl ohexane, derived from compound 3 by
      catalytic hydrogenation, is stable against enzymic cleavage and competitively
      inhibits beta-D-galactosidase from Escherichia coli with a Ki-value of 5.5 mM.
      Sigmatropic rearrangement of 3 in methanolic solution partially led to an
      unseparable mixture of the regioisomers (3,5/4,6)-3,4-diazido-5-O-(beta-D
      galactopyranosyl)-6-hydroxycy clohexene and (3,5/4,6)-3,4-diazido-6-O-(beta-D
      galactopyranosyl)-5-hydroxycy clohexene. Catalytic hydrogenation thereof yielded
      an equally unseparable mixture of the diamines (1,3/2,4)-1,2-diamino-4-O-(beta-D
      galactopyranosyl)-4-hydroxycyclohex ane and (1,3/2,4)-1,2-diamino-4-O-(beta-D
      galactopyranosyl)-3-hydroxycyclohex ane, inhibiting beta-D-galactosidase
      competitively with K(i) 0.9 mM.

PMID- 8536256
TI  - A bi-fluorescence-labeled substrate for ceramide glycanase based on fluorescence
      energy transfer.
AB  - An alkyl lactoside containing two different fluorescence probes as an energy
      donor and an energy acceptor was synthesized as a substrate for ceramide
      glycanase. n-Pentenyl beta-lactoside was converted into its 4',6'-O-(2
      naphthylmethylidene) derivative with subsequent benzoylation of all remaining OH
      groups. The fully protected lactoside was treated with borane-trimethylamine
      complex and aluminum chloride in tetrahydrofuran [P.J. Garegg, Pure Appl. Chem.,
      56 (1984) 845-858] for selective opening of the 4',6'-acetal group to give the 6'
      O-(2-naphthylmethyl) derivative in high yield. After O-debenzoylation, the omega
      alkenyl group at the reducing end was extended by Michael addition with
      HS(CH2)2NH2.HCl to provide an amino group at the terminal position. The amino
      group was then dansylated to give the target lactoside, which has two different
      fluorescent probes at each end. Excitation at 290 nm (of the 2-naphthyl group) of
      the bi-fluorescence-labeled lactoside showed emissions at 335 nm (2-naphthyl) and
      at 540 nm (dansyl). The distance between the naphthyl group and the dansyl group
      was estimated to be 12 A by the Forster relationship. Digestion of this lactoside
      with American leech (Macrobdella decora) ceramide glycanase [B. Zhou et al., J.
      Biol. Chem., 264 (1989) 12,272-12,277] resulted in an increase in the naphthyl
      emission with a concomitant decrease in the dansyl emission. These changes can be
      used for continuous monitoring of the ceramide glycanase activity.

PMID- 8536257
TI  - Spacer-modified oligosaccharides with basic anchoring groups are inhibitors for
      endo-glycanases: porcine pancreatic alpha-amylase as model enzyme.
AB  - By coupling methyl 2,3,6-tri-O-acetyl-4-O-(5-azido-6-p-tolylsulfonyloxyhexyl)
      alpha-D - glucopyranoside with 2-benzoylthioethyl 2,3,4,6-tetra-O-acetyl-alpha-D
      glucopyranoside, a spacer-modified disaccharide derivative, methyl 4-O-(5-azido-9
      alpha-D-glucopyranosyloxy-7-thianonyl)-alpha- D-glucopyranoside, was obtained and
      then enzymatically glucosylated to yield the spacer-modified tri- and tetra
      saccharide methyl 4-O-(5-azido-9-alpha-maltosyloxy-7-thianonyl)-alpha-D-glucop
      yranoside and methyl 4-O-(5-azido-9-alpha-maltotriosyloxy-7-thianonyl)-alpha-D-gl
      ucopyranoside, respectively, the extended spacer spanning the length of two (1-
      >4)-linked pyranosyl units. The corresponding amines methyl 4-O-(5-amino-9-alpha
      D-glucopyranosyloxy-7-thianonyl)-alpha- D-glucopyranoside, methyl 4-O-(5-amino-9
      alpha-maltosyloxy-7-thianonyl)-alpha-D-glucop yranoside and methyl 4-O-(5-amino-9
      alpha-maltotriosyloxy-7-thianonyl)-alpha-D-gl ucopyranoside, obtained by
      catalytic reduction, carry the basic functionality in a spacer position to allow
      ionic interaction with a catalytically active acidic group in porcine pancreatic
      alpha-amylase (PPA). Optimal inhibition of enzymic activity is by methyl 4-O-(5
      amino-9-alpha-maltosyloxy-7-thianonyl)-alpha-D-glucop yranoside where three of
      the five subsites are occupied by glucosyl units and the spacer spanning the
      remaining subsites positions the amino group near the catalytic site.

PMID- 8536258
TI  - Mono-, di- and tri-antennary D-galactose ligands as competitive inhibitors and
      photoaffinity labels of the hexose transporting system in erythrocytes. A model
      for the irreversible blocking of receptors in cell membranes.
AB  - Starting from pentaerythritol, photolabile mono-, di-, and tri-dentate galactose
      derivatives as well as their 3H-labelled isotopomers were synthesised. The
      hydrophilic chains linking the 6 position of D-galactose to pentaerythritol
      consist of 13 atoms in line. The mono-, di- and tri-dentate compounds, although
      themselves not transported, inhibit in increasing order 14C-D-galactose transport
      into erythrocytes. On irradiating whole cells in the presence of ligand with 350
      nm UV light, these compounds also in increasing order, could irreversibly block
      the hexose transport system. Irradiation without ligand has no effect. By using
      the 3H-labelled tridentate galactose compound the hexose transporter (zone 4.5)
      is specifically radiolabelled, as could be shown in an SDS-PAGE of membrane
      proteins from erythrocytes previously photoaffinity labelled. Radiolabelling is
      significantly suppressed in the presence of D-glucose.

PMID- 8536259
TI  - Synthesis of 5-deoxy-5-epifluoro derivatives of arbekacin, amikacin, and 1-N-[(S)
      4-amino-2-hydroxybutanoyl]tobramycin (study on structure--toxicity
      relationships).
AB  - As part of a study on fluorination--toxicity relationships for aminoglycoside
      antibiotics, 5,3'-dideoxy-5-epifluorokanamycin B (10), 5,3',4'-trideoxy-5
      epifluorokanamycin B (11), 1-N-[(S)-4-amino-2-hydroxybutanoyl]-5-deoxy-5
      epifluorotobramyc in (19), 5-deoxy-5-epifluoroarbekacin (20), and 5-deoxy-5
      epifluoroamikacin (21) have been prepared. The acute toxicities of these three 5
      deoxy-5-epifluoro compounds showed values almost identical or similar to those
      for arbekacin (ABK) and amikacin (15), making a sharp contrast with the
      toxicities of the corresponding 5-deoxy-5-fluoro derivatives. This fact is
      explained on the basis of basicity changes (retention for the 5-epifluoro
      derivatives and reduction for the 5-fluoro derivatives) at the H2N-3 groups of
      the fluorinated compounds compared to the parent compounds; this hypothesis was
      substantiated by the pKa values at the H3N(+)-1, 3 groups (determined by the
      shift changes depending on pD values at C-2 and C-4, 6 in their 13C NMR spectra)
      of 2,5-dideoxy-5-epifluorostreptamine (23) and 2,5-dideoxy-5-fluorostreptamine
      (24), chosen as model compounds, and 2-deoxystreptamine (DST).

PMID- 8536260
TI  - Methyl 3-amino-3-deoxy-beta-D-galactopyranosyl-(1-->4)-2-acetamido-2- deoxy-beta
      D-glucopyranoside: an inhibitor of UDP-D-galactose: beta-D-galactopyranosyl-(1-
      >4)-2-acetamido-2-deoxy-D-glucose (1-->3)-alpha-D-galactopyranosyltransferase.
AB  - UDP-D-galactose:beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy-D- glucose
      alpha-(1-->3)-D-galactopyranosyltransferase [E.C. 2.4.1.151] transfers D
      galactosyl-residues from the sugar nucleotide with retention of configuration. We
      report here that synthetic methyl 3'-amino-3'-deoxy-N-acetyllactosaminide (9),
      where the hydroxyl group normally undergoing galactosylation has been replaced by
      amino group, is an inhibitor for this enzyme with Ki = 104 microM. The mode of
      inhibition is not competitive, but appears to be specific, since other
      glycosyltransferases were not affected by 9.

PMID- 8536261
TI  - Versatile intermediates in the selective modification of the amino function of 2
      amino-2-deoxy-D-mannopyranose and the 3-position of 2-acetamido-2-deoxy-D
      mannose: potential membrane modifiers in neoplastic control.
AB  - A general method has been developed to selectively modify the amino group of 2
      amino-2-deoxy-D-mannopyranose (D-mannosamine), a precursor of the terminal
      membrane sugar, sialic acid. 1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-alpha-D
      mannopyranose oxalate was prepared via two routes that allowed introduction of
      various acyl groups onto the amino function. These compounds were evaluated for
      their antineoplastic properties. The most significant preclinical therapeutic
      finding was the antileukemic activity found in mice for tetra-O-acetyl-2-epi
      streptozotocin (the acetylated alpha-mannosamine epimer of streptozotocin).
      Administration of 50 mg/kg/day x 5 to leukemia L1210-bearing DBA/2Ha mice
      resulted in 5/5 35-day survivors. Neutralization of 1,3,4,6-tetra-O-acetyl-2
      amino-2-deoxy-alpha-D-mannopyranose oxalate under aqueous conditions led to 2
      acetamido-1,4,6-tri-O-acetyl-2-deoxy-alpha-D-mannopyranose, the oxidation of
      which gave 2-acetamido-4,6-di-O-acetyl-1,5-anhydro-2-deoxy-D-erythro-hex-1-en-3-
      ulose. This agent demonstrated an IC50(2) of 25 microM with a murine L1210 cell
      culture. Administration of 100 mg/kg/day x 5 resulted in 42% ILS3 in DBA/2 mice
      with ip L1210 leukemia. Several other nonacetylated derivatives were also
      prepared by direct N-acylation, producing, for example, fluorescently tagged N
      dansylmannosamine.

PMID- 8536262
TI  - Synthesis of the tetrasaccharide repeating unit of the antigen from Klebsiella
      type 2.
AB  - The disaccharide ethyl 2,4,6-tri-O-acetyl-3-O-(2,3,4,6-tetra-O-benzyl-alpha- D
      glucopyranosyl)-1-thio-beta-D-glucopyranoside (6) and methyl 2,6-di-O-benzyl-3-O
      (methyl 2,3,4-tri-O-benzyl-alpha-D- glucopyranosyluronate)-beta-D-mannopyranoside
      (21) have been synthesized and condensed in the presence of methyl triflate to
      afford a tetrasaccharide derivative. Removal of protecting groups gave methyl 3-O
      (methyl alpha-D-glucopyranosyluronate)-4-O-(3-O-alpha-D- glucopyranosyl-beta-D
      glucopyranosyl)-beta-D-mannopyranoside (23), the repeating unit of the antigen
      from Klebsiella type 2, in the form of its methyl ester methyl glycoside.

PMID- 8536263
TI  - The dependence of glucan conformational dynamics on linkage position and
      stereochemistry.
AB  - The 13C NMR T1 relaxation times for the (1-->4)-linked maltooligomers (Mi) and
      the (1-->6)-linked isomaltooligomers (IMi) with i = 2, 4, 6, and 8 were measured
      in aqueous solution at 22 and 65 degrees C at a concentration (3%) low enough to
      have removed concentration-dependent effects on the measured T1 values. Separate
      T1 values were measured for each carbon in the residue at the reducing end of the
      oligosaccharide, in the residue at the non-reducing end, and in the interior,
      i.e., non-terminal, residue(s). Analogous data for the corresponding high
      polymers show that at 22 degrees C the relaxation times for the carbons of the
      interior residues of the oligomers have converged to their high chain length
      asymptotes at about i = 10. This observation suggests that at room temperature
      polymeric motions in the frequency domain effective for 13C NMR relaxation at a
      magnetic field strength of 11.7 T have a "wavelength" of the order of 10
      residues. The relaxation times characterizing the two ends of the chain are
      different, with longer T1 values for the carbons of the reducing end than for
      those of the non-reducing end. Carbons of alpha-anomeric residues at the reducing
      end have shorter relaxation times than those of the corresponding beta-anomeric
      reducing sugars. Carbons of the interior residues have T1 values shorter than the
      carbons of either type of terminal residue. For oligomers of a given dp there is
      no T1 difference between oligomers of the Mi and IMi series at room temperature.
      This observation is seemingly at odds with the great differences in the inherent
      conformational freedom of the (1-->4)- and (1-->6)-linkages. At elevated
      temperatures the orientational relaxation behavior of the two series of oligomers
      measured by 13C T1 values show interesting differences, and in the case of the Mi
      series, structure develops in the chain length dependence of the T1 values.

PMID- 8536264
TI  - Larch arabinogalactan for hepatic drug delivery: isolation and characterization
      of a 9 kDa arabinogalactan fragment.
AB  - Purified arabinogalactan [AG(37 kDa)] from Larix occidentalis is composed of
      repeating units of similar molecular weight and composition. A 9 kDa
      arabinogalactan [AG(9 kDa)] has been obtained in high yield from AG(37 kDa)
      either by autoclaving at 121 degrees C or by exposure to alkaline solution in the
      presence of sodium borohydride. The weight average molecular weight of AG(37
      (kDa) was determined to be 37 and 38 kDa by intensity light scattering and
      sedimentation equilibrium, respectively. The weight average molecular weight of
      AG(9 kDa) was determined to be 9.1 and 9.5 kDa by intensity light scattering and
      sedimentation equilibrium, respectively. MALDI-TOF mass spectrometry yielded a
      molecular weight at the peak of the distribution of 8.3 kDa for AG(9 kDa). Both
      AG(37 kDa) and AG(9 kDa) exhibited narrow molecular-weight distributions (Mw/Mn
      approximately 1.2). AG(37 kDa) and AG(9 kDa) exhibit nearly identical 13C-NMR
      spectra, monosaccharide composition, and sugar linkages. It is proposed that
      AG(37 kDa) is composed of covalently bound subunits of AG(9 kDa). AG(37 kDa) and
      AG(9 kDa) bind isolated hepatocyte asialoglycoprotein receptor equally well. As a
      result AG(9 kDa) is a candidate for use in hepatocyte directed drug delivery and
      may be more desirable for such use than is AG(37 kDa).

PMID- 8536265
TI  - Isolation and characterization of novel heterogeneous branched cyclomalto
      oligosaccharides (cyclodextrins) produced by transgalactosylation with alpha
      galactosidase from coffee bean.
AB  - Transgalactosylated derivatives of cyclomalto-hexaose (alpha CD), -heptaose (beta
      CD), and -octaose (gamma CD) were synthesized by alpha-galactosidase from coffee
      bean using melibiose as a donor and alpha CD, beta CD or gamma CD as an acceptor.
      Mono- and di-O-alpha-D- galactosylated CDs were isolated and purified by HPLC.
      Their structures were elucidated by fast-atom bombardment mass spectrometry
      (FABMS) and 13C NMR spectroscopy. For structural determination of positional
      isomers of 6(1),6n-di-O-alpha-D-galactosyl-CDs, digestion products with
      cyclodextrin glucanotransferase were analyzed by HPLC and FABMS.

PMID- 8536266
TI  - Structural studies of the extracellular polysaccharide from Butyrivibrio
      fibrisolvens strain 49.
AB  - The structure of Butyrivibrio fibrisolvens strain 49 capsular polysaccharide has
      been investigated mainly by sugar and methylation analysis, partial chemical
      degradations, NMR spectroscopy, and mass spectrometry. The results suggest that
      the polysaccharide is composed of pentasaccharide repeating units having the
      following structure. [formula: see text] The polysaccharide contains O-acetyl
      groups, one of which is substituted to O-3 of the 4-substituted alpha-D-Galp
      residue, while others occur in non-stoichiometric amounts at other locations.

PMID- 8536267
TI  - NMR investigation of the 6-deoxy-L-talose-containing O45, O45-related (O45rel),
      and O66 polysaccharides of Escherichia coli.
AB  - The structures of the 6-deoxytalose-containing O-specific polysaccharides from
      the O45 antigen, an O45-related antigen (O45rel), and the O66 antigen
      (lipopolysaccharides, LPSs) of Escherichia coli were elucidated by chemical
      characterization and by one- and two-dimensional 1H and 13C NMR spectroscopy. The
      O45 and O45-related polysaccharides have the following general structure:
      [formula: see text] For the O45 antigen, X is alpha-D-FucpNAc and for the O45
      related antigen, X is beta-D-GlcpNAc. The structure of the O66 polysaccharide is
      [formula: see text]

PMID- 8536268
TI  - Analogues of disaccharides and glycosides containing a cyclic guanidinium
      structure show varying inhibitory effects on glycoside hydrolases.
AB  - By condensation of 1,3-diamino-2,4-(R)-O-benzylidene-1,3-dideoxy-D-erythritol (3)
      and 1,3-diamino-2,4-di-O-benzyl-1,3-dideoxy-D-threitol (4) with methyl 2,3,6-tri
      O-benzyl-4-deoxy-4-iso-thiocyanato-beta-D-glucopyranosid e (9) the (1-->4)-linked
      disaccharide analogues 4-deoxy-4-[(4R,5S)-5-hydroxy-4-(hydroxymethyl)-1,4,5,6
      tetrahydropyri midin-2- yl[amino-alpha,beta-D-glucopyranose hydrochloride (15)
      and 4-deoxy-4-[(4R,5R)-5-hydroxy-4-(hydroxymethyl)-1,4,5,6-tetrahydropyri midin-
      2-yl]amino-alpha,beta-D-glucopyranose hydrochloride (18) were synthesized. By the
      same reaction sequence, using 3 and methyl isothiocyanate, the glycoside analogue
      (4R,5S)-5-hydroxy-4-(hydroxymethyl)-2-methylamino-1,4,5,6- tetrahydropyrimidine
      hydrochloride (20) was obtained. All compounds possess in their 'glyconic' moiety
      the flat guanidinium group, mimicking a glucopyranosyl cation. Together with the
      previously synthesized (1-->6)-linked disaccharide analogues 6-deoxy-6-[(4R,5S)-5
      hydroxy-4-(hydroxymethyl)-1,4,5,6- tetrahydropyrimidin-2-yl]amino-alpha,beta-D
      glucopyranose hydrochloride (1) and 6-deoxy-6-[(4R,5R)-5-hydroxy-4-(hydroxy
      methyl)-1,4,5,6- tetrahydropyrimidin-2-yl]amino-alpha,beta-D-glucopyranose
      hydrochloride (2), a possible inhibitory effect on the action of alpha-D
      glucosidase, beta-D-glucosidase, alpha-D-galactosidase, and beta-D-galactosidase
      was investigated. All compounds, except 20 with alpha-D-glucosidase where no
      inhibition could be detected, showed either competitive or mixed competitive
      inhibition with all enzymes. The effects of the disaccharide analogues were
      generally weaker as compared to the effect of the previously synthesized
      configurationally related nitrophenyl glycoside analogues (4R,5S)-5-hydroxy-4
      (hydroxymethyl)-2-(p-nitrophenyl)amino-1,4,5,6- tetrahydropyrimidine
      hydrochloride (21) and (4R,5R)-5-hydroxy-4-(hydroxymethyl)-2-(p-nitrophenyl)amino
      1,4,5,6- tetrahydropyrimidine hydrochloride (22). On the basis of experimental
      results, different binding hydrochloride (22). On the basis of experimental
      results, different binding modes of competitive inhibitors to the active site of
      corresponding enzymes are discussed.

PMID- 8536269
TI  - Hydration of alpha-maltose and amylose: molecular modelling and thermodynamics
      study.
AB  - Hydration of alpha-maltose and amylose were investigated using molecular
      modelling and thermodynamics methods. The structure and energy of hydration of
      three low-energy conformers of alpha-maltose were determined by the MM3 molecular
      mechanics method. The hydration structure was found to be sensitive to the
      conformation of alpha-maltose and hydration numbers 10 or 11 were estimated for
      the different conformers. Differential scanning calorimetry and thermogravimetric
      analysis were used to determine the number of water molecules specifically bonded
      (non-freezing water) to amylose and different samples of alpha-maltose. Due to
      high crystallinity of alpha-maltose samples, the observed non-freezing water
      content was lower than predicted by molecular modelling. In contrast, the
      experimental number of non-freezing molecules of water per D-glucopyranose
      residue for amorphous amylose (nh = 3.8) is in good accordance with the value of
      3.8 extracted from our calculations.

PMID- 8536270
TI  - 4,6-O-benzylidene-D-glucopyranose and its sodium salt: new data on their
      preparation and properties.
AB  - An improved method for the preparation of 4,6-O-benzylidene-D-glucopyranose (BG),
      and new or correlated data on its 1H and 13C NMR spectra, specific rotations, and
      tautomeric equilibria, and on those of its anomeric sodium salt (BGNa), are
      reported. Evidence is presented in favour of the hypothesis that crystalline BGNa
      exists entirely in its beta-anomeric form and that it can be useful in the access
      to beta-glucosides in reactions with strong electrophiles under strictly
      heterogeneous conditions.

PMID- 8536271
TI  - Tumor cells engineered to produce cytokines or cofactors as cellular vaccines: do
      animal studies really support clinical trials?

PMID- 8536272
TI  - High-dose continuous venous infusion of interleukin-2: influence of dose and
      infusion rate on tumoricidal function and lymphocyte subsets.
AB  - Previous clinical studies have demonstrated a dose-response relationship between
      enhancement of certain immune parameters and interleukin-2 (IL-2) dose in trials
      with low dosages of the cytokine. This has not been demonstrated for high-dose
      (greater than 18 x 10(6) IU/m2 per day) IL-2. We completed phase II trials of
      sustained administration of indomethacin and ranitidine with IL-2 given as a
      continuous infusion over 5 days for three courses. Peripheral blood mononuclear
      cells, both fresh and cultured in vitro with IL-2 or IL-2 and indomethacin, were
      tested for tumoricidal function against K562 and Daudi targets; these results
      were then correlated with actual delivered dose and mean infusion rate per
      course. Similar correlations were calculated between delivered dose or infusion
      rate and absolute and proportional counts of lymphocyte subsets as determined by
      flow cytometry. No enhancement of in vitro tumoricidal function with either
      increasing delivered dose or increasing infusion rate was seen. No consistent
      pattern of correlation was found between the absolute counts of lymphocyte
      subsets after each course of IL-2 with delivered dose or infusion rate. The
      percent rise in absolute counts of selected T- and NK-cell subsets at the end of
      course 1 compared with baseline values correlated positively with infusion rate;
      however, a similar correlated between the infusion rate and an increase in
      lymphocyte tumoricidal function was lacking. Little evidence was found for
      improved tumoricidal function of mononuclear cells or consistent enhancement of
      lymphocyte subset counts in patients able to tolerate doses of IL-2 beyond 18 x
      10(6) IU/m2 per day in a 5-day continuous infusion schedule.

PMID- 8536273
TI  - A flow cytometric study of c-erbB-3 expression in breast cancer.
AB  - In order to assess the specificity of biotinylated anti-c-erbB-3 antibody,
      screening was performed on a series of tumour cell lines and lymphocytes.
      Staining was found to be consistent, with good reproducibility. Twenty-nine
      consecutive breast cancer samples were obtained from women treated with tamoxifen
      and undergoing elective mastectomy. Twenty-eight invasive ductal carcinomas and 1
      DCIS were stained for c-erbB-3 expression: 2 were grade I (Bloom and Richardson),
      15 grade II, and 11 grade III tumours, 1 being unclassified; 16 were axillary
      node positive and 10 node negative; in 2 cases no nodes were sampled. Tumours
      examined by flow cytometry were stained with cytokeratin FITC antibody and the
      cytokeratin-positive population gated. Using Mann-Whitney analysis no association
      was seen between c-erbB-3 expression and Bloom and Richardson grade or axillary
      node status. In the tumour samples c-erbB-3 expression was found to show as
      association with EGF-R (P = 0.021 r2 = 0.16), PgR (P = 0.02, r2 = 0.16), c-myc (P
      < 0.0001, r2 = 0.5), c-jun (P = 0.001, r2 = 0.4) and c-fos (P = 0.001, r2 = 0.5)
      but not with c-erbB-2 (P = 0.2, r2 = 0.06), ER (P = 0.4, r2 = 0.02) or p53 1801
      (P = 0.05, r2 = 0.2). Expression of c-erbB-3 may not be an independent marker of
      prognosis, but it is associated with other markers of poor prognosis and early
      cellular events linked with aberrant growth and differentiation.

PMID- 8536274
TI  - Therapy with interleukin-2 induces the systemic release of phospholipase-A2.
AB  - Therapy with interleukin-2 (IL-2) induces remissions in some forms of cancer.
      This treatment however, is accompanied by side-effects which, in part, may be
      mediated by the formation of eicosanoids and platelet-activating factor. We
      investigated the systemic release of phospholipase A2 (PLA2), a rate-limiting
      enzyme in the formation of these lipid mediators, in patients receiving IL-2. In
      a pilot study of 4 patients we observed an increase in PLA2 activity in serial
      plasma samples obtained during the first day after a bolus infusion of IL-2,
      which increase closely correlated with that of antigen levels of secretory
      phospholipase A2 (sPLA2) as measured by enzyme-linked immunosorbent assay (r =
      0.92; P < 0.001). In 20 patients, receiving 12 x 10(6)-18 x 10(6) IU IL-2/m2, we
      then investigated the course of antigenic levels of sPLA2 in relation to those of
      the cytokines tumour necrosis factor alpha (TNF) and interleukin-6 (IL-6) (both
      cytokines may induce sPLA2 in vivo). From 4 h on, sPLA2 levels significantly
      increased, reaching a peak 24 h after the IL-2 infusion. Subsequent IL-2
      infusions even induced a further increase of sPLA2. This increase of sPLA2 was
      presumably not due to a direct effect of IL-2 on, for example, hepatocytes, since
      this cytokine, in contrast to IL-1, IL-6, TNF and interferon gamma, was not able
      to induce the synthesis of sPLA2 by Hep G2 cells in vitro. Consistent with this,
      plasma levels of TNF and IL-6 in the patients rose, reaching peak levels before a
      zenith of sPLA2 occurred, i.e. at 2 h and 4 h after the start of the IL-2
      infusion respectively. sPLA2 levels significantly correlated with the development
      of the side-effects increase in body weight (r = 0.49; P < 0.0001) and decrease
      in mean arterial blood pressure (r = 0.40; P < 0.0001). Moreover, maximum sPLA2
      levels induced by IL-2 were higher in patients who had progressive disease after
      therapy than in patients who had stable disease or a partial response.

PMID- 8536276
TI  - Anti-(transforming growth factor beta) antibodies with predefined specificity
      inhibit metastasis of highly tumorigenic human xenotransplants in nu/nu mice.
AB  - Monoclonal antibodies (mAb) were prepared against conjugated transforming growth
      factor beta 1 (TGF beta 1) peptides: amino acid positions 48-60 and positions 86
      101. Two antibodies, mAb 16-3G1 [anti-(48-60)] and mAb 5-2G6 [anti-(86-101)]
      cross-reacted with native TGF beta 1, -beta 2 and -beta 3 (16-3G1) or only with
      native TGF beta 1 (5-2G6). Both mAb were used to characterize TGF beta-mediated
      effects on the metastatic potential in nude mice of human carcinoma cell line SLU
      1 and its metastatic subline SLU-M1. Autocrine TGF beta 1-mediated up-regulation
      of cell proliferation and its suppression by anti-TGF beta antibodies in vitro
      was recorded for SLU-M1 cells whereas SLU-1 cell proliferation in vitro appeared
      to be refractory to anti-TGF beta antibodies and exogenous TGF-beta 1. However,
      the potential of s.c. tumours to develop distant metastases in nude mice was
      about the same for both cell lines. Development of primary tumours and distant
      metastases could be suppressed by treatment of mice with anti-TGF beta
      antibodies. Thus we assume that the metastatic potential of tumour cells is
      independent of TGF beta-mediated growth-regulation effects in vitro. The anti-TGF
      beta-induced suppression of tumour progression and metastasis in nude mice might
      rather result from stimulation of the immune surveillance. TGF beta-mediated
      autocrine down-regulation of MHC-unrestricted cytotoxicity of activated human
      monocytes and CD56+ LAK cells and its reversion by anti-TGF beta antibodies could
      be readily demonstrated. In all our experimental series, the neutralizing
      potential of both anti-TGF beta antibodies, though directed against opposite
      sites of the TGF beta 1 molecule, was very similar.

PMID- 8536275
TI  - Culture of tumour-infiltrating lymphocytes from melanoma and colon carcinoma:
      removal of tumour cells does not affect tumour-specificity.
AB  - The therapeutic potential of adoptive therapy using tumour-infiltrating
      lymphocytes (TIL) has been demonstrated in a number of clinical trials. However,
      freshly isolated tumour-infiltrating lymphocytes (TIL) are often impaired in
      their proliferative and cytotoxic responses, which limits their use in
      immunotherapy. Several hypotheses with regard to the poor effector function of
      TIL have been postulated, including the production of immunosuppressive factors
      by tumour cells. In a previous paper we reported the efficient expansion of
      immunoreactive TIL from a variety of solid tumours by stimulation with a
      combination of monoclonal antibodies (mAbs) against CD3 and CD28. In the present
      study we analysed whether this protocol would be improved by the removal of
      tumour cells at the start of the culture. We tested a highly immunogenic tumour,
      melanoma, and a poorly immunogenic tumour, colon carcinoma. Removal of tumour
      cells highly improved anti-CD3/CD28 stimulated expansion of TIL from colon
      carcinoma, resulting in a significantly higher percentage of potentially tumour
      specific CD8-positive T-cells and a reduced CD4/CD8 ratio compared to expansion
      in the presence of tumour cells. In contrast, expansion and CD4/CD8 ratio of
      melanoma-derived TIL was not significantly influenced by the removal of
      autologous tumour cells. CD3/CD28-stimulated melanoma TIL cultured in the absence
      of tumour cells showed specific lysis of autologous tumour cells comparable to
      melanoma TIL cultured in high-dose IL2. However, no cytotoxicity could be
      detected in colon TIL irrespective of the culture conditions used. On the other
      hand, 3/8 colon carcinoma TIL cultures and 9/12 melanoma-derived TIL cultures
      showed IFN gamma secretion upon stimulation with autologous tumour cells. We
      conclude that stimulation of TIL with a combination of mAbs to CD3 and CD28 in
      the absence of tumour cells induces efficient expansion of potentially tumour
      specific cells from a highly and a poorly immunogenic tumour. Removal of tumour
      cells does not have a negative influence on the generation of tumour-specific T
      cells, while cell yield improves. Therefore, for large-scale cultures this
      protocol can efficiently induce the outgrowth of tumour-specific TIL, at the same
      time providing a useful source of autologous tumour cells that can be stored and
      used to direct or test antitumour specificity.

PMID- 8536277
TI  - Antiproliferative effects of bacillus Calmette-Guerin and interferon alpha 2b on
      human bladder cancer cells in vitro.
AB  - Direct inhibitory effects of bacillus Calmette-Guerin (BCG) and interferon alpha
      2b (IFN alpha 2b) on six human bladder carcinoma cell lines, UCRU-BL-13, UCRU-BL
      17, UCRU-BL-28, 5637, T24 and J82, were studied using an in vitro proliferation
      assay. Effects on proliferation following exposure to BCG or IFN alpha 2b were
      analysed by [3H]thymidine incorporation over 7 days. BCG had an antiproliferative
      effect on all bladder lines, while sensitivity to IFN alpha 2b varied greatly,
      being as remarkably low as 1 U/ml for some lines. The antiproliferative effect
      was greatest when cells were exposed continuously to either agent, but was still
      evident with a limited exposure. When clinical concentrations were simulated in
      vitro, BCG+IFN alpha 2b was more effective than BCG alone and as effective as a
      double BCG concentration. We conclude that, in addition to their immunomodulatory
      effects, BCG and IFN alpha 2b directly inhibit the proliferation of human bladder
      cancer cells, and often at extremely low concentrations.

PMID- 8536279
TI  - [The cardiac fossa].

PMID- 8536278
TI  - Tumor-specific granulocyte/macrophage colony-stimulating factor and interferon
      gamma secretion is associated with in vivo therapeutic efficacy of activated
      tumor-draining lymph node cells.
AB  - In this study, cytokine release by tumor-draining lymph node cells sensitized in
      vitro (IVS-TDLN) was examined and correlated with therapeutic efficacy in
      adoptive immunotherapy. Mice bearing immunologically distinct MCA 207 and MCA 205
      sarcoma tumors were utilized in criss-cross experiments. IVS-TDLN obtained from
      mice bearing 10-day subcutaneous (s.c.) tumors mediated immunologically specific
      regression of established 3-day pulmonary metastases, but demonstrated non
      specific cytolytic reactivity against both tumors in a 4-h 51Cr-release assay. By
      contrast, these IVS-TDLN cells were found specifically to secrete
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma
      (IFN gamma) when restimulated in vitro with irradiated tumor cells. To determine
      the predictive value of tumor-specific cytokine release with in vivo therapeutic
      efficacy, a kinetic analysis of antitumor activities of TDLN obtained from
      animals bearing MCA 207 tumors for increasing lengths of time was performed. IVS
      TDLN cells from mice bearing day-7, -10 and -14 s.c. tumors manifested tumor
      specific release of GM-CSF and IFN gamma, and mediated significant antitumor
      reactivity in vivo. In contrast IVS-LN cells from day-0 and day-21 tumor-bearing
      animals did not release significant amounts of GM-CSF and IFN gamma, and were not
      therapeutically efficacious in vivo. Day-4 IVS-TDLN released high levels of GM
      CSF and IFN gamma non-specifically, and were not therapeutic in adoptive
      immunotherapy at doses effective for day-7 and day-14 IVS-TDLN cells. In other
      experiments, IVS cells generated from different lymph node groups in animals
      bearing 10-day established s.c. tumors were examined and found to have unique
      profiles of cytokine release. In these studies, the ability of IVS cells to
      release specifically both cytokines as opposed to one was associated with greater
      therapeutic efficacy on a per cell basis. Our findings suggest that the tumor
      specific releases of GM-CSF and IFN gamma are useful parameters to assess the in
      vivo therapeutic efficacy of immune lymphocytes.

PMID- 8536280
TI  - [Diabetic cardiopathy].

PMID- 8536281
TI  - [Cardiac magnetic resonance: the technical indications and a technical glossary].

PMID- 8536282
TI  - Noninvasive measurement of cardiac output.

PMID- 8536283
TI  - Medical treatment of pulmonary hypertension.

PMID- 8536284
TI  - [The physiopathological role and prognostic value of the vasoactive intestinal
      peptide in acute myocardial infarct].
AB  - Aim of our study was to investigate the pathophysiological role of vasoactive
      intestinal peptide (VIP) in the neuroendocrine activation occurring in acute
      myocardial infarction (AMI). Plasma VIP concentration has been assayed in 30
      patients with AMI, 22 males and 8 females, aged 41-82 years, without other
      important diseases. VIP plasma values, assayed on admission to the Coronary Care
      Unit, within 4-6 hours after the onset of chest pain, everyday for the first week
      and on day 14, were significantly higher in survivors and in patients aged < 60
      years. VIP plasma concentration was not statistically correlated with CPK and CPK
      MB. VIP seems to play a pathophysiological role in the neuroendocrine activation
      occurring in AMI. Low VIP plasma levels are associated with an unfavorable short
      term prognosis. Moreover, it appears that VIP secretion is negatively influenced
      by aging.

PMID- 8536285
TI  - [The usefulness of noninvasive diagnostic methods in postinfarct prognostic
      stratification].
AB  - We have studied 455 consecutive patients with acute myocardial infarction to
      assess the early and mid-term prognostic value of clinical and laboratory
      findings in the acute (i.e. Killip classification, arterial PO2,
      echocardiographic extent of necrotic area) and subacute phase (exercise test,
      ambulatory ECG). Results showed that clinical examination, blood gas analysis and
      two-dimensional echocardiography have a high predictivity for in-hospital risk
      stratification. In particular, two-dimensional echocardiography showed that
      patients with diffuse wall motion abnormalities had a worse prognosis during the
      follow-up. Exercise test and, to a lesser extent, ambulatory ECG have well
      identified patients at risk for new coronary events.

PMID- 8536286
TI  - [The organizational and technical aspects of transcatheter ablation in cardiac
      arrhythmias. A document of the Gruppo Italiano di Aritmologia with a contribution
      of the Assoziazione Italiana di Cardiostimolazione under the aegis of the Societa
      Italiana di Cardiologia and of the Associazione Nazionale Medici Cardiologi
      Ospedalieri].

PMID- 8536287
TI  - [A double ventricular obstruction in a case of hypertrophic cardiomyopathy].
AB  - The authors report the case of a young woman with hypertrophic obstructive
      cardiomyopathy and double left ventricular obstruction (midventricular and
      subaortic). This young woman was also affected by mild aortic coarctation. Both
      abnormalities were diagnosed by means of echocardiography. Doppler
      echocardiography revealed unusual intracavitary signals and the presence of two
      distinct intracardiac obstructive flows.

PMID- 8536288
TI  - [Intravascular coronary ultrasonography].

PMID- 8536289
TI  - What is the physiological role of the trigeminovascular system?

PMID- 8536290
TI  - Neuropeptides and migraine--a useful biological marker?

PMID- 8536291
TI  - Cervical headache.

PMID- 8536292
TI  - Children and criteria for migraine.

PMID- 8536293
TI  - Migraine and cluster headache--their management with sumatriptan: a critical
      review of the current clinical experience.
AB  - Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which
      mediates constriction of certain large cranial blood vessels and/or inhibits the
      release of vasoactive neuropeptides from perivascular trigeminal axons in the
      dura mater following activation of the trigeminovascular system. The mode of
      action of this drug in migraine and cluster headache is discussed. On the basis
      of a detailed review of all published trials and available data from post
      marketing studies, the efficacy, safety, tolerability and the place of oral and
      subcutaneous sumatriptan in the treatment of both conditions are assessed. A
      number of double-blind clinical trials have demonstrated that sumatriptan 100 mg
      administered orally is clearly superior to placebo in the acute treatment of
      migraine headache and achieves significantly greater response rates than
      ergotamine or aspirin. In other studies, 70 to 80% of patients receiving
      sumatriptan 6 mg sc experienced relief of migraine headaches by 1 or 2 h after
      administration, and patients consistently required less rescue medication for
      unresolved symptoms. Sumatriptan was also effective in relieving associated
      migraine symptoms like nausea and vomiting. Sumatriptan was equally effective
      regardless of migraine type or duration of migraine symptoms. Overall,
      approximately 40% of patients who initially responded to oral or subcutaneous
      sumatriptan experienced recurrence of their headache usually within 24 h,
      effectively treated by a further dose of this drug. In 75% of patients with
      cluster headache treated with sumatriptan 6 mg sc, relief was achieved within 15
      min. Based on pooled study data, sumatriptan is generally well tolerated and most
      adverse events are transient. Adverse events following oral administration
      include nausea, vomiting, malaise, fatigue and dizziness. With the subcutaneous
      injection, injection site reactions occur in approximately 30%. Chest syumptoms
      are reported in 3 to 5% but have been associated with myocardial ischaemia only
      in rare isolated cases. The recommended dosage of sumatriptan at the onset of
      migraine symptoms is 100 mg orally or 6 mg subcutaneously. The recommended dosage
      for cluster headache is 6 mg sumatriptan sc. Sumatriptan must not be given
      together with vasoconstrictive substances, e.g., ergotamines, or with migraine
      prophylactics with similar properties, e.g., methysergide. Sumatriptan should not
      be given during the migraine aura. It is contraindicated in patients with
      ischaemic heart disease, previous myocardial infarction, Prinzmetal (variant)
      angina and uncontrolled hypertension.

PMID- 8536294
TI  - Migraine: association with personality characteristics and psychopathology.
AB  - The relationship between migraine and psychopathology has been discussed far more
      often than it has been systematically studied. Twentieth-century investigators
      have frequently described the obsessional rigid, angry personality postulated to
      characterize migraine sufferers. More recent population-based studies have
      demonstrated associations between migraine and depression and migraine and panic
      disorder. This article discusses the relationship of migraine and personality and
      migraine and psychopathology.

PMID- 8536295
TI  - Brown-Sequard's comment on Du Bois-Reymond's "hemikrania sympathicotonica".
AB  - In 1859 the famous physiologist Du Bois-Reymond, a migraine sufferer, stated that
      migraine could be due to an increased sympathicotonic influence on the blood
      vessels of one side of the head. Migraine, he thought, was not a disease of the
      brain or cranial blood vessels, but of the cilio-spinal center in the spinal
      cord. The physician and physiologist Brown-Seqard, who, independently from Claude
      Bernard, discovered and interpreted the action of the vasomotor nerves in the
      early 1850s, commented on Du Bois-Reymond's paper, stating that irritation of the
      cervical sympathetic does not cause pain. From his great experience from animal
      experiments and clinical observations he had concluded that stimulation of the
      cervical sympathetic would cause epileptic seizures, rather than migraine
      attacks. He felt that Du Bois-Reymond's observations would better fit a
      sympathico-paralytic model of migraine. He was seconded by other physicians like
      Mollendorff, until Latham tried to unify both theories.

PMID- 8536296
TI  - Modification of vasoconstrictor responses in cerebral blood vessels by lesioning
      of the trigeminal nerve: possible involvement of CGRP.
AB  - The functional role of the trigeminal system has been addressed in experiments on
      the cortical surface of alpha-chloralose anaesthetized cats. Application of
      calcitonin gene-related peptide (CGRP) caused a concentration-dependent increase
      in arteriolar calibre by 38 +/- 5% (n = 8) with an IC50 of 2 nM. Cerebral veins
      did not relax upon CGRP administration (n = 12). Substance P (SP) was less potent
      but showed dilatation of both arterioles (21 +/- 4%) and veins (16 +/- 4%). The
      cerebrovascular trigeminal system was investigated after chronic (14 days)
      surgical lesion of the trigeminal nerve with the concomitant disappearance of
      perivascular CGRP/SP immunoreactive nerves. The cortical arteriolar responses to
      subarachnoid microinjections of acidic (pH 6.8) and basic CSF (pH 7.6) as well as
      noradrenaline (10(-4) M), neuropeptide Y (10(-7) M), prostaglandin F2x (10(-6 M),
      barium chloride (10(-4) M), and autologous blood (5 microl) were examined in
      anaesthetized cats with lesions of the trigeminal nerve, and were compared with
      their effects in sham-operated animals. The magnitude of the vasodilator and
      vasoconstrictor responses to these agents was unaffected by trigeminal lesions.
      However, duration of the vasoconstriction produced by basic CSF, but not the
      vasodilitation to acidic CSF, was markedly prolonged by trigeminal lesions (from
      0.8 +/- 0.1 min to 2.2 +/- 0.3 min, p < 0.01). Also, the vasoconstrictor
      responses to noradrenaline, prostaglandin F2x, barium chloride, and autologous
      blood were significantly prolonged, while the maximum contractile effect to each
      agent was similar in lesioned as in sham-operated controls. The effects of CGRP,
      SP, and neurokinin A (NKA) have been examined on isolated cerebral arteries in
      vitro. Different CGRP analogues induced a strong relaxation with no difference in
      Imax (85-96%) or pD2 values (8.65 - 9.12). NKA induced a stronger relaxation than
      SP (Imax: 33% and 13%, respectively). SP was more potent than NKA (pD2:8.7 and
      7.7, respectively). Capsaicin, a substance which selectively causes the release
      of stored sensory neuropeptides (CGRP, SP, NKA), caused in vitro relaxation of
      precontracted arteries. This relaxation was not affected by the neurokinin
      blocker spantide, but shifted towards higher capsaicin concentrations by the CGRP
      antagonist (CGRP 8-37. Thus, in this preparation CGRP rather than a neurokinin
      (SP/NKA) is responsible for the capsaicin-induced dilatations.

PMID- 8536297
TI  - Vasoactive peptide levels in the plasma of young migraine patients with and
      without aura assessed both interictally and ictally.
AB  - We measured, by RIA methods, ictal and interictal levels of substance P (SP),
      calcitonin-gene related peptide (CGRP) and neurokinin A (NKA) in the plasma of 30
      young migraine patients with aura (MPA) and 45 migraine patients without aura
      (MWA), and compared the results with those of 30 age-matched controls. There were
      no significant differences between the levels of these vasoactive peptides in the
      control group and the levels in both migraine groups studied in headache-free
      periods. An elevation of CGRP levels in plasma was found during attacks in MPA
      and, to a lesser extent, in MWA (p < 0.03 and p < 0.05, respectively). A
      significant increase in NKA levels was also demonstrated in the MPA and MWA
      groups (p < 0.02 and p < 0.04, respectively). These data suggest, although
      indirectly, that CGRP and NKA could be involved in the pathogenesis of migraine
      attacks in juvenile migraine patients.

PMID- 8536298
TI  - Diagnostic value of C2-3 instantaneous axes of rotation in patients with headache
      of cervical origin.
AB  - Previous investigators have suggested that patients suffering headache stemming
      from the C2-3 segment of the cervical spine can be identified by detecting an
      abnormal axis of rotation of that segment. The present study tested this
      hypothesis by correlating the location of the instantaneous axis of rotation
      (IAR) of the C2-3 segment with diagnostic blocks of the C2-3 zygapophysial joint
      in a sample of patients with headache. We found no significant correlation
      between the location of the axis and the response to diagnostic blocks. Previous
      false-positive assertions appear to be due to insufficient attention to the
      precision and reproducibility of the techniques used to determine IARs.

PMID- 8536299
TI  - Responses to temporal visual stimuli in migraine: the critical flicker fusion
      test.
AB  - Reports of sensitivity to striped patterns and to flickering lights are not
      uncommon in migraineurs. Only recently, however, have objective methods been used
      to assess the visual sensitivity of these patients, with emphasis on their
      responses to spatial stimuli; responses to temporal information have been largely
      neglected on an experimental level. The "critical flicker fusion" (CFF) test was
      performed by 25 migraineurs with aura, 25 migraineurs without aura, and 25
      control subjects. The CFF test is a quick, simple technique which provides
      information concerning the temporal responsiveness of the visual system; a
      sensitivity threshold is measured. A significant group difference between the
      migraineurs without aura and the control subjects emerged (p = 0.01). Control
      subjects had the highest CFF threshold, migraineurs with aura the next highest,
      and migraineurs without aura the lowest threshold.

PMID- 8536300
TI  - Transcranial Doppler ultrasound in migraine and tension-type headache after
      apomorphine administration: double-blind crossover versus placebo study.
AB  - The effect of the dopaminergic agonist apomorphine on blood velocity in the
      middle cerebral artery has been studied in patients with migraine, tension-type
      headaches, and healthy subjects by means of transcranial Doppler monitoring.
      Following the administration of apomorphine, systolic velocity and mean velocity
      significantly increased and pulsatility index significantly decreased in
      migraineurs compared to placebo and to the other groups of subjects. These
      changes were dose-dependent and showed a time-curved compatible with the
      pharmacokinetic profile of the drug. The different effect of apomorphine in
      migraineurs compared with controls and tension-type headache patients implies
      that migraineurs have increased sensitivity to dopaminergic stimuli and suggests
      that transcranial Doppler monitoring after apomorphine administration could be a
      useful tool in the evaluation of migraineurs.

PMID- 8536301
TI  - Effect of age on the fulfilment of the IHS criteria for migraine in children at a
      headache clinic.
AB  - In a headache clinic, 247 children suffering from severe recurrent headaches were
      studied in relation to the IHS criteria for migraine. Of the 247, 163 had
      migrainous headache, with 100 (67.5%) of these having migraine in accordance with
      the IHS criteria. The remaining 53 (32.5%) had headache attacks fulfilling all
      but one of the IHS criteria. Coverage of the IHS criteria for migraine was 93%.
      Symptoms of unilateral headache, aggravation by physical activity, and nausea
      showed the greatest differences in frequency between those with migraine and
      those with probable migraine. All children with aura fulfilled criteria for
      migraine. Children with migraine with aura (11.8, 95% CI: 11.0-12.6 years) were
      older than those without aura (10.1, 9.4-10.8 years; p = 0.001). Children with
      pulsating headache were slightly older than children without pulsating headache.
      No differences in age were detected with other IHS criteria.

PMID- 8536302
TI  - Headache in lacunar stroke.
AB  - The presence of headache within a 72-h interval of stroke onset was investigated
      in a cohort of 145 lacunar infarcts. Fourteen (10%) experienced diffuse or
      bilateral headache. Hypertension was less frequent (43 vs 76%; 95% CI: 6 to 60%)
      and of shorter duration (2.4 vs 7.8 years; t = 2.29; p = 0.02) among patients
      with headache. Leukoaraiosis was less frequent (40% vs 71%; 95% CI: -57 to -7%)
      and severe (7 vs 24%; 95% CI: -33 to -2%) in patients with headache. Age, sex,
      stroke risk factors, type of lacunar stroke, mode of onset, stroke severity,
      ultrasound and other CT findings were similar in patients with and without
      headache. No differences in the sixth month neurological or functional outcome
      were detected between lacunar patients with and without headache. Headache in
      lacunar stroke cannot be predicted by the clinical characteristics of the stroke
      and is not due to coexisting cardiembolism, intra or extracranial disease.
      Hypertensive small-vessel disease is less common and severe in lacunar strokes
      with associated headache.

PMID- 8536303
TI  - Health-related quality of life under six months' treatment of migraine--an open
      clinic-based longitudinal study.
AB  - Health-related quality of life (HQL) assessment in the clinical setting have
      distinguished subjective perceptions (e.g., well-being), signs/symptoms of the
      disease and functional capacity as three major components. The impact of short
      term treatment for migraine attacks on these variables was evaluated in an open
      prospective 6-month study at the Gothenburg Migraine Clinic. Socio-economic
      factors, subjective symptoms, and general well-being/quality of life were
      evaluated by self-administered questionnaires in 99 patients with migraine with
      or without aura in accordance with the classification of the International
      Headache Society. Short-term treatment comprising conventional therapy or
      subcutaneous sumatriptan reduced number of days per month with migraine and
      absenteeism from work, migraine-associated symptoms, but did not significantly
      improve general well-being between attacks. Future assessment of the patients'
      HQL in accordance with this approach would enable us to consider all the
      advantages and disadvantages of current therapies of particular interest in the
      field of migraine.

PMID- 8536304
TI  - Introduction of a novel self-injector for sumatriptan. A controlled clinical
      trial in general practice.
AB  - A novel self-injector for the administration of subcutaneous sumatriptan in the
      treatment of migraine attacks was tested in 138 patients recruited by family
      physicians in Denmark: 108 patients completed the initial double-blind, crossover
      part of the study. Sumatriptan 6 mg s.c. was significantly better than placebo at
      30, 60, 90 and 120 min after injection in relieving moderate or severe headache
      to mild or none as well as relieving any headache to none. At 60 min after
      injection, the treatment response rate was 61% for sumatriptan and 6% for
      placebo. During the following open-phase trial of four attacks treated with
      sumatriptan, treatment response rates were 68-74%. During the total of 538
      attacks treated, 12 attempts at using the self-injector failed. In the double
      blind and open phases, 81% and 90% of patients respectively found the device easy
      or very easy to use. Adverse effects were benign and short-lasting, but led seven
      patients to discontinue the study. In conclusion, subcutaneous sumatriptan
      administered with a novel self-injector is an effective treatment for migraine
      compared to placebo in patients treated by their family physician.

PMID- 8536305
TI  - Efficacy of transdermal clonidine in short-term treatment of cluster headache: a
      pilot study.
AB  - Some clinical as well as pharmacological indications seem to suggest that a
      reduction of the noradrenergic tone occurs in cluster headache (CH), during both
      the active and remission periods. But sharp fluctuations of the sympathetic
      system may trigger the attacks. Clonidine, an alpha-2-adrenergic presynaptic
      agonist, regulates the sympathetic tone in the central nervous system. Therefore,
      a continuous administration of low-dose clonidine could be potentially beneficial
      in the active phase of CH by antagonizing the variations in noradrenergic tone.
      After a run-in week, we administered transdermal clonidine (5 - 7.5 mg) for one
      week to 13 patients suffering from CH, either episodic (8 cases) or chronic (5
      cases). During clonidine treatment, the mean weekly frequency of attacks dropped
      from 17.7 +/- 7.0 to 8.7 +/- 6.6 (p = 0.0005), the pain intensity of attacks
      measured on the visual analogue scale from 98.0 +/- 7.2 to 41.1 +/- 36.1 mm (p =
      0.001), and the duration from 59.3 +/- 21.9 to 34.3 +/- 24.6 min (p = 0.02). This
      open pilot study strongly suggests that transdermal clonidine may be an effective
      drug in the preventive treatment of CH. Its efficacy is possibly due to its
      central sympatho-inhibition, which reduces or prevents the occurrence of
      fluctuations of noradrenaline release that may induce the attacks.

PMID- 8536306
TI  - The 7th International Headache Congress. Toronto, Ontario, Canada. September 16
      20, 1995. Abstracts.

PMID- 8536307
TI  - Functional analysis of the ABF1-binding sites within the Ya regions of the MATa
      and HMRa loci of Saccharomyces cerevisiae.
AB  - Cell type in the yeast Saccharomyces cerevisiae is determined by information
      present at the MAT locus. Cells can switch mating types when cell-type
      information located at a silent locus, HML or HMR, is transposed to the MAT
      locus. The HML and HMR loci are kept silent through the action of a number of
      proteins, one of which is the DNA-binding protein, ABF1. We have identified a
      binding site for ABF1 within the Ya region of MATa and HMRa. In order to examine
      the function of this ABF1-binding site, we have constructed strains that lack the
      site in the MATa or HMRa loci. Consistent with the idea that ABF1 plays a
      redundant role in silencing, it was found that a triple deletion of the ABF1
      binding sites at HMRE, Ya and I did not permit the expression of HMRa. We have
      also shown that chromosomal deletion of the binding site at MATYa had no effect
      on the level of cutting by the HO endonuclease nor on the amount of mating-type
      switching observed. Similarly, chromosomal deletion of all three ABF1-binding
      sites at HMRa had no effect on the directionality of mating-type switching.

PMID- 8536308
TI  - Mating-type suppression of the DNA-repair defect of the yeast rad6 delta mutation
      requires the activity of genes in the RAD52 epistasis group.
AB  - The RAD6 gene of Saccharomyces cerevisiae is required for post-replication repair
      of UV-damaged DNA, UV mutagenesis, and sporulation. Here, we show that the
      radiation sensitivity of a MATa rad6 delta strain can be suppressed by the MAT
      alpha 2 gene carried on a multicopy plasmid. The a1-alpha 2 suppression is
      specific to the RAD6 pathway, as mutations in genes required for nucleotide
      excision repair or for recombinational repair do not show such mating-type
      suppression. The a1-alpha 2 suppression of the rad6 delta mutation requires the
      activity of the RAD52 group of genes, suggesting that suppression occurs by
      channelling of post-replication gaps present in the rad6 delta mutant into the
      RAD52 recombinational repair pathway. The a1-alpha 2 repressor could mediate this
      suppression via an enhancement in the expression, or the activity, of
      recombination genes.

PMID- 8536309
TI  - The evolutionary relationships between homologs of ribosomal YL8 protein and YL8
      like proteins.
AB  - We previously reported the sequence of YL8A, one of the two genes encoding yeast
      ribosomal protein YL8. With the aim of conducting an evolutionary study we have
      cloned and sequenced a second gene, YL8B. The disruption of both genes is lethal.
      Unlike other duplicated ribosomal protein genes, each open reading frame is
      interrupted by two introns containing long conserved sequences. A comparison of
      nucleotide and amino-acid sequences reveals that the duplication of the YL8 gene
      must have occurred very recently. Alignment and phylogenetic analysis of the
      amino-acid sequences of YL8-related proteins from various species show the
      existence not only of YL8 ribosomal proteins but also of a family of YL8-like
      proteins. These are present in at least three species of yeast and seem to be
      functionally distinct from ribosomal proteins.

PMID- 8536310
TI  - Cloning and analysis of the nuclear gene MRP-S9 encoding mitochondrial ribosomal
      protein S9 of Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae nuclear gene MRP-S9 was identified as part of the
      European effort in sequencing chromosome II. MRP-S9 encodes for a hydrophilic and
      basic protein of 278 amino acids with a molecular mass of 32 kDa. The C-terminal
      part (aa 153-278) of the MRP-S9 protein exhibits significant sequence similarity
      to members of the eubacterial and chloroplast S9 ribosomal-protein family. Cells
      disrupted in the chromosomal copy of MRP-S9 were unable to respire and displayed
      a characteristic phenotype of mutants with defects in mitochondrial protein
      synthesis as indicated by a loss of cytochrome c oxidase activity. Additionally,
      no activities of the gluconeogenetic enzymes, fructose-1,6-bisphosphatase and
      phosphoenolpyruvate carboxykinase, could be observed under conditions of glucose
      de-repression. The respiration-deficient phenotype could not be restored by
      transformation of the disruption strain with a wild-type copy of MRP-S9,
      indicating that MRP-S9 disruption led to rho- or rho0 cells. Sequence
      similarities of MRP-S9 to other members of the ribosomal S9-protein family and
      the phenotype of disrupted cells are consistent with an essential role of MRP-S9
      is assembly and/or function of the 30s subunit of yeast mitochondrial ribosomes.

PMID- 8536311
TI  - Schizosaccharomyces pombe pac2+ controls the onset of sexual development via a
      pathway independent of the cAMP cascade.
AB  - The Schizosaccharomyces pombe pac2 gene encodes a protein of 235 amino acids not
      similar to any protein of known function. Cells over-expressing pac2 were poor in
      mating and sporulation. Expression of ste11, which encodes a key transcription
      factor for sexual development, was not inducible by nitrogen starvation in these
      cells. Cells defective in pac2 could express ste11 and enter sexual development
      under incomplete starvation conditions. Although expression of ste11 is regulated
      primarily by the cAMP cascade, genetic analysis indicated that this cascade and
      pac2 can partially compensate for each other in the regulation of sexual
      development, and that neither of them is epistatic over the other. Thus, Pac2
      appears to control ste11 expression via a signaling pathway independent of the
      cAMP cascade.

PMID- 8536312
TI  - The complete mitochondrial DNA sequence of Hansenula wingei reveals new
      characteristics of yeast mitochondria.
AB  - The complete 27,694-bp mitochondrial (mt) DNA sequence of Hansenula wingei, which
      is a typical budding yeast and contains circular mitochondrial DNA, has been
      determined. The mt sequence contains genes encoding large and small ribosomal
      RNAs, 25 tRNAs, three subunits of cytochrome c oxidase (subunits 1, 2 and 3),
      three subunits of ATPase (subunits 6, 8 and 9), apocytochrome b, seven subunits
      of NADH dehydrogenase (subunits 1, 2, 3, 4, 4L, 5 and 6), and a ribosomal
      protein, VAR1. The VAR1 gene is considered to be a typical yeast type. This is
      consistent with data on DNA and the deduced amino-acid sequence homology
      comparisons of genes ubiquitous in yeast and fungi. However, we have identified
      seven genes encoding NADH dehydrogenase subunits, which are not found in other
      yeast mitochondrial genomes, thus placing the H. wingei mitochondrial genome in a
      unique position. In addition the H. wingei mitochondrial genome also encodes one
      tRNA pseudogene and one short unidentified ORF. The genome is compact with only
      two introns both of which contain an ORF. One intron lies in the large rRNA gene
      while the other is situated in the cytochrome c oxidase subunit-1 gene. The
      conserved nonanucleotide motif (A/T)TATAAG (T/A)(A/T), which is a transcription
      start signal in Saccharomyces cerevisiae mitochondria, has also been found in the
      H. wingei mitochondrial genome. The codon assignments for ATA and CTN in H.
      wingei mitochondria are different from those in S. cerevisiae mitochondria. These
      results indicate a unique and novel structure for the H. wingei mitochondrial
      genome in terms of characteristics which are typical for both yeast and for
      filamentous fungi. This is the first complete mt DNA sequence report in yeast.

PMID- 8536313
TI  - Nucleotide-sequence analysis indicates that a DNA plasmid in a diseased isolate
      of Ophiostoma novo-ulmi is derived by recombination between two long repeat
      sequences in the mitochondrial large subunit ribosomal RNA gene.
AB  - The nucleotide sequence of a mitochondrial plasmid (2234 bp) in a diseased
      isolate of Ophiostoma novo-ulmi, and sequences of the mitochondrial DNA that
      overlap and flank the plasmid end-points, have been determined. The plasmid was
      shown to be derived from the O. novo-ulmi mitochondrial large subunit ribosomal
      RNA gene and contained most of intron 1, the whole of exon 2, and probably the
      first part of intron 2. Within intron 1 there is an open reading frame with the
      potential to encode a 323 amino-acid polypeptide which contained dodecapeptide
      sequences typical of RNA maturases and DNA endonucleases. The endpoints of the
      plasmid in the mtDNA were located within two 90-bp direct imperfect repeat
      sequences, one of which comprised the last 7 bp of exon 1 and the first 83 bp of
      intron 1 whilst the other comprised the last 7 bp of exon 2 and the first 83 bp
      of intron 2. It is proposed that the Ld plasmid was generated by intramolecular
      recombination between these two repeats with the crossover point probably within
      the last 15 bp.

PMID- 8536314
TI  - A point mutation in the 5'-untranslated leader that affects translational
      activation of the mitochondrial COX3 mRNA.
AB  - The 613-base 5'-untranslated leader (5'-UTL) of the Saccharomyces cerevisiae
      mitochondrial COX3 mRNA contains the target of an mRNA-specific translational
      activator complex composed of at least three nuclearly encoded proteins. We have
      genetically mapped a collection of cox3 point mutations, using a set of defined
      COX3 deletions, and found one to be located in the region coding the 5'-UTL. The
      strain carrying this allele was specifically defective in translation of the COX3
      mRNA. Nucleotide-sequence analysis showed that the allele was in fact a double
      mutation comprised of a single-base insertion in the 5'-UTL (T inserted between
      bases -428 and -427 with respect to the start of translation) and a G to A
      substitution at +3 that changed the ATG initiation codon to ATA. Both mutations
      were required to block translation completely. The effects of the ATG to ATA
      mutation alone (cox3-1) had previously been analyzed in this laboratory: it
      reduces, but does not eliminate, translation, causing a slow respiratory growth
      phenotype. The T insertion in the 5'-UTL had no detectable respiratory growth
      phenotype as a single mutation. However, the 5'-UTL insertion mutation enhanced
      the respiratory defective phenotype of missense mutations in pet54, one of the
      COX3-specific translational-activator genes. This phenotypic enhancement suggests
      that the -400 region of the 5'-UTL, where the mutation is located, is important
      for Pet54p-COX3 mRNA interaction.

PMID- 8536315
TI  - Analysis of the transcription products of the rainbow trout (Oncorynchus mykiss)
      liver mitochondrial genome: detection of novel mitochondrial transcripts.
AB  - We have isolated and, by electrophoresis, using agarose slab gels in the presence
      of methylmercury hydroxide, analyzed the mitochondrial RNA content of the liver
      of rainbow trout. The RNAs corresponding to most of the mitochondrial DNA-encoded
      genes have been identified. Furthermore, among the transcription products we have
      also identified the nature of the RNA 8 previously described in human
      mitochondria, and detected a novel transcript that may represent the mRNA for
      ND6.

PMID- 8536316
TI  - Multiple roles of the cellulase CBHI in enhancing production of fusion antibodies
      by the filamentous fungus Trichoderma reesei.
AB  - The production of Fab antibody fragments in Trichoderma reesei can be increased
      over 50-fold by fusing the core-linker region of the T. reesei cellulase CBHI
      (cellobiohydrolase I) to the heavy Fd chain (Nyyssonen et al. 1993). This
      beneficial role of CBHI in antibody production has now been studied further by
      comparisons of T. reesei trains producing the light chain only. Fab or CBHI-Fab
      all of which exhibited identical light chain integration. The N-terminal fusion
      of CBHI to the heavy Fd chain not only aided secretion, as expected, but also
      increased the level of mRNA encoding the CBHI-heavy Fd chain, either by
      stabilizing the messenger or by enhancing transcription. The CBHI part appeared
      to facilitate secretion at least by aiding the passage through the endoplasmic
      reticulum, since processing of the signal peptide of the antibody chains seemed
      to be most efficient in the strain producing CBHI-Fab in contrast to the strains
      producing light chain or Fab fragment. Interestingly, CBHI core-linker protein,
      originating from the CBHI-heavy Fd chain, was found in large amounts in the
      culture medium. The cleavage resulting in this tailless CBHI occurred inside the
      cell. This suggests that, by omitting the heterologous tail, the secretion of the
      resulting CBHI core-linker protein is enhanced to a level comparable with
      secretion of the extracellular T. reesei proteins.

PMID- 8536317
TI  - Characterization of the "promoter region" of the enolase-encoding gene enol from
      the anaerobic fungus Neocallimastix frontalis: sequence and promoter analysis.
AB  - The sequence of the Neocallimastix frontalis enolase gene promoter was determined
      up to 1800 nucleotides 5' to the major transcriptional start point. The base
      composition of the enolase upstream sequence revealed a very A + T-rich profile
      (13.5% G + C) leading to many putative hairpin structures. The functional
      organization of the N. frontalis enolase promoter was investigated by
      heterologous transient-expression assays. DNA fragments obtained by the
      sequential removal of sequences upstream of the translation start codon were
      fused to the Escherichia coli lacZ gene and the resulting plasmids were used to
      transform the ascomycetes Aspergillus nidulans and Penicillium roqueforti and the
      oomycete Saprolegnia monoica. Transient expression of the lacZ reporter gene was
      observed in regenerating proteoplasts of S. monoica when using the 0.3 kb or 1 kb
      upstream of the enolase coding region. In contrast no beta-galactosidase activity
      was detected in ascomycete protoplasts. DNA hybridization analysis revealed the
      integration of vector DNA in the genomic DNA of S. monoica and the presence of
      free copies of the transformation plasmid which could be rescued in E. coli. Our
      results indicate that the transcriptional machinery of the anaerobic chytrid N.
      frontalis may differ significantly from that of ascomycetes but that enough
      conservation exists within the lower fungi to allow a transient-driven expression
      of a reporter gene in an oomycete fungus.

PMID- 8536318
TI  - Recombinational stability of replicating plasmids in Aspergillus nidulans during
      transformation, vegetative growth and sexual reproduction.
AB  - Plasmids containing the AMA1 replicon are capable of autonomous maintenance in
      Aspergillus nidulans. It has been reported previously that these plasmids can
      form concatenates by recombination in a transformed mycelium, and up to 10% of
      molecules are involved in such events. The present study demonstrates that
      plasmid recombination, although frequent during transformation, rarely occurs
      during vegetative growth. As a result, the structure and phenotypic stability of
      AMA1 plasmids generally remains unaltered for many asexual (conidial)
      generations. It is also evident that plasmid replication does not require
      specific recombination events in the AMA1 palindrome. However, during sexual
      reproduction, autonomous plasmids exhibit increased recombination, which results
      in both plasmid concatenation and integration into the chromosome.

PMID- 8536319
TI  - Nucleotide sequence of the sheep mitochondrial DNA D-loop and its flanking tRNA
      genes.
AB  - The nucleotide sequence of the sheep mitochondrial DNA displacement-loop (D-loop)
      region and its flanking tRNA genes has been determined. Several conserved motifs
      among mammals have been identified along the 1189-bp sequence of the sheep
      control region: ten termination-associated sequences (TASs) and one conserved
      sequence block (CSB-1). CSB-2 and CSB-3, which are frequently found in most
      species, are not present in the sheep D-loop, which shows instead a short direct
      repeat at their usual localization. A long polypyrimidine tract between CSB-1 and
      the tRNA(Phe) gene is also present. Furthermore, the sheep mtDNA D-loop region
      displays tandem repeats in the left domain (adjacent to the tRNA(Pro) gene)
      comprising three different termination-associated sequences (TAS-5, TAS-6 and TAS
      7).

PMID- 8536320
TI  - Intron-encoded open reading frame of the GIY-YIG subclass in a plastid gene.
AB  - Group-I introns, containing open reading frames (ORFs) that code for homing
      endonucleases, are widely distributed amongst eukaryotic organellar genomes.
      However, endonucleases of the GIY-YIG subclass have a restricted distribution in
      mitochondria and bacteriophages, and have never been observed in plastids. We
      have found the GIY-YIG motif in an intronic ORF within the previously published
      psbA gene sequence from Chlamydomonas reinhardtii chloroplasts. Based on
      phylogenetic analysis and an evaluation of amino-acid substitutions, this ORF is
      not closely related to any of the other GIY-YIG ORFs. These results suggest that
      GIY-YIG ORFs have a longer evolutionary history than previously assumed.

PMID- 8536321
TI  - The Stamy procedure: a retrospective analysis of clinical outcome in stress
      incontinence.
AB  - OBJECTIVE: To review the clinical outcome of treatment by the modified Stamy
      procedure in 26 patients with genuine stress incontinence. DESIGN: A
      retrospective study of women with stress incontinence who underwent a modified
      Stamy procedure over a 2-year period between January 1991 and January 1993, of
      postoperative complications and the success rate three months after surgery.
      SUBJECTS: Twenty-six women presenting with symptomatic stress incontinence.
      INTERVENTIONS: All patients underwent a modified Stamy procedure. They were
      reviewed in the gynaecology clinic after three months. MAIN OUTCOME MEASURES: All
      patients were assessed by clinical examination for postoperative complications,
      subsequent voiding difficulties, and for recurrence or persistence of
      incontinence. RESULTS: The most common complications were retention of urine
      (23%), infection (19%), postoperative persistent pain (12%), urge incontinence
      (8%) and primary haemorrhage requiring transfusion (4%). The stress incontinence
      was subjectively cured in 81% and objectively cured in 72% when examined at three
      months postoperatively. CONCLUSIONS: Modified Stamy procedure is a useful
      operation for women with stress incontinence and it is associated with a low
      incidence of postoperative complications.

PMID- 8536322
TI  - A locally made mucus aspirator.
AB  - Examination of nasopharyngeal aspirate for the presence of viral antigens in
      children with acute lower respiratory tract infections is a standard procedure in
      establishing a viral aetiology. In the absence of other sophisticated methods
      such as lung puncture or trans-tracheal aspiration, mucopus aspirated from the
      nasopharynx can be used even to identify caustive organisms. Here, it is
      essential to perform a microscopic examination in addition to culture. The
      disposable mucus aspirators used in other countries are expensive and are not
      practical for routine use in our country. This paper describes how a mucus
      aspirator was turned out with low cost heat resistant materials that are locally
      available. The aspirator is steam sterilisable and can be used with a disposable
      F8 gauge feeding tube. The cost of one aspirator is about Rs. 100.

PMID- 8536323
TI  - Emergency femoral arteriography in lower limb vascular trauma.
AB  - There are difficulties in obtaining emergency arteriographic evaluation in lower
      limb vascular trauma even in the best centres in the world. Ten emergency room
      arteriograms were performed at the new Accident Service of the General Hospital,
      Colombo from February to October 1992 by the vascular team, using a venous
      cannula and improvised tubing systems. The indications were, absence of distal
      pulses with closed injury to the limb, previous attempts at repair, injury to the
      limb at more than one site and multiple shrapnel injury. A traumatic
      arteriovenous communication was shown in one of the arteriograms. Unnecessary
      exploration of the artery was prevented by the demonstration of a patent
      femoropopliteal segment in two cases. The average delay caused by this procedure
      was less than one hour, which compares well with centres in the West. Provision
      of an arteriogram kit at the Accident Service will help to overcome practical
      problems.

PMID- 8536324
TI  - The health services of Sri Lanka present and future.
AB  - 1) Sri Lanka has achieved a high human development status; 2) The health sector,
      and particularly the government health sector, has played an important role in
      this achievement. 3) The health transition is going to increase the burden of
      disease and the demand for health services; 4) The government health services
      have been underfunded and the provincial health services have been more
      underfunded; 5) The most cost efficient health services, anywhere in the world,
      are government funded; 6) Therefore, it is our duty to lobby government to
      increase government funding for health services; 7) The preventive health service
      should continue to be funded fully by government. Prevention of non-communicable
      diseases should come within this orbit. Staff in preventive health services
      should be better remunerated; 8) The essential clinical package in the periphery
      must be improved to reduce by-passing and underutilization; 9) Management of
      tertiary health care facilities have to be strengthened. They should be given
      responsibility and autonomy; 10) A powerful unit should be established in the
      Ministry to study and implement cost recovery and cost containment in tertiary
      care institutions; 11) Senior doctors should take an active part in the
      management of the tertiary care institutions to make them more efficient. 12)
      Private hospitals should be supervised by the Ministry in order to ensure quality
      of care and to contain national health care costs:

PMID- 8536325
TI  - Is it Munchausen syndrome by proxy?
AB  - We describe two cases of children who were victims of illness fabricated by their
      mothers. Such clinical situations are identified as Munchausen syndrome by proxy
      (MSP). Although considered a form of child abuse, MSP often goes unrecognised in
      paediatric practice. The two children involved were unnecessarily investigated,
      and the underlying problems in the mothers were identified only after several
      hospital admissions. One mother had a major psychiatric disorder, and the other
      had serious marital problems. Maintaining a high degree of suspicion regarding
      inexplicable illness in a child with inappropriate or incongruous symptoms and
      signs, even when parents behave in an exemplary manner, would help in early
      diagnosis and management.

PMID- 8536326
TI  - Delayed recovery after spinal anaesthesia using 0.5% cinchocaine.

PMID- 8536327
TI  - Inadvertent cannulation of the intercostal vein.

PMID- 8536328
TI  - The blood revolution initiated by the famous footnote of Karl Landsteiner's 1900
      paper.
AB  - A 1900 publication authored by Karl Landsteiner, at the age of 32 years,
      contained a footnote which stated that, "the serum of healthy human beings not
      only agglutinates animal red cells, but also often those of human origin, from
      other individuals". He followed up this statement in his 1901 paper, and
      concluded that, "My observations reveal characteristic differences between blood
      serum and red blood cells of various apparently healthy persons" and that "the
      reported observations may assist in the explanation of various consequences of
      therapeutical blood transfusions". These significant observations resulted in the
      discovery of A, B, O and AB blood groups and later led to successful blood
      transfusions in humans. The impact of the revolutionary finding by Landsteiner
      also changed a number of biomedical disciplines such as immunochemistry, medical
      anthropology, forensic medicine, genetics and pathology.

PMID- 8536329
TI  - Sarcoid-like granulomas of the skin seven years after bomb blast injury.

PMID- 8536330
TI  - Prevention of AIDS in Sri Lanka: are we doing the best for our people?

PMID- 8536331
TI  - Need for change in female sterilisation procedure and selection.

PMID- 8536332
TI  - Remedy for dilution errors in ESR.

PMID- 8536334
TI  - An optimistic approach to treatment of vitiligo.

PMID- 8536333
TI  - The GATT TRIPS agreement and health care in India.

PMID- 8536335
TI  - Protective effective of vitamin E in kidney storage solution on renal tissue
      metabolism in rats.
AB  - OBJECTIVE: To determine whether inclusion of vitamin E into kidney storage
      solutions protects metabolism and tubular ultrastructure of stored rat kidney.
      METHODS: Rat kidneys were flush stored in Marshall's Citrate (MC) and MC +
      vitamin E (25% of LD 50 and 50% of LD 50) for 24 hours at 0 degrees C. After
      storage kidney slices were tested for gluconeogenesis and lactate dehydrogenase
      (LDH) activity, and examined for cellular ultrastructure. RESULTS: Kidneys stored
      in MC + vitamin E gave higher gluconeogenesis than those stored in MC alone (p <
      0.001). Tubular ultrastructure was better preserved in the presence of Vitamin E.
      CONCLUSIONS: Vitamin E appears to protect the metabolism and ultrastructure of
      stored rat kidneys.

PMID- 8536336
TI  - Binding specificity of mutagenic tryptophan pyrolysates for DNA conformation:
      spectroscopic and viscometric studies.
AB  - The compounds, 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), are major potent mutacarcinogens
      isolated from tryptophan pyrolysate. In order to investigate their interaction
      with DNA and effects on DNA conformation, studies involving circular dichroism,
      fluorescence and absorption spectroscopy and viscometric titration were
      performed. The results show that (a) Trp-P-1 and Trp-P-2 are potent intercalators
      of DNA with nearly the same specificity for the A-T and G-C (alternative purine
      pyrimidine) base sequences, (b) the interaction of Trp-P-1 with the B-form of DNA
      is biphasic so that stiffening of the B-DNA conformation occurs over the range r
      ([Trp-P-1]/[DNA]) = 0-2.5, followed by transformation of B to the non-B
      conformation at r > 2.5, (c) the transformation to the non-B structure is not
      observed for Trp-P-2, although stiffening of the B-DNA conformation similarly
      occurs, and (d) both Trp-P-1 and Trp-P-2 promote unwinding of the salt-induced Z
      DNA to give the B-form. These data indicate that the noncovalent interaction of
      Trp-P with DNA is mainly dependent on the B-form conformation.

PMID- 8536337
TI  - Synthesis of a novel dual inhibitor of thromboxane A2 synthetase and 5
      lipoxygenase (E3040) via the direct coupling reaction of hydroquinone with 3
      pyridinecarboxaldehyde.
AB  - Synthesis of a novel dual inhibitor of thromboxane A2 synthetase and 5
      lipoxygenase, 5,7-dimethyl-6-hydroxy-2-methylamino-4-(3-
      pyridylmethyl)benzothiazole (E3040), was accomplished via a new coupling
      reaction, in which a key intermediate, (3,6-dihydroxy-2,4-dimethylphenyl)-(3
      pyridyl)methanol, was easily synthesized in a high yield from 2,6-dimethyl-1,4
      benzohydroquinone and 3-pyridinecarboxaldehyde in 6 N hydrochloric acid. The
      regio isomers of 3-pyridinecarboxaldehyde also gave the corresponding coupling
      products in high yields.

PMID- 8536338
TI  - Syntheses, immunosuppressive activity, and structure-activity relationships of
      myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxyomyriocin, and nor
      deoxomyriocins.
AB  - Nine myriocin analogs, 2-epi-myriocin, 14-deoxomyriocin, Z-14-deoxomyriocin, and
      nor-deoxomyriocins, were synthesized from 2-deoxy-D-glucose via common
      intermediates used in previous myriocin and Z-myriocin syntheses.
      Immunosuppressive activities of those myriocin analogs on mouse allogeneic mixed
      lymphocyte reaction were examined, and Z-14-deoxomyriocin was found to show the
      most potent activity among them. The structure-activity relationships are
      discussed.

PMID- 8536339
TI  - Studies on metabolites of mycoparasitic fungi. IV. Minor peptaibols of
      Trichoderma koningii.
AB  - Three minor peptaibols, trichokonins (TKs)-Ia, Ib, and IX, were obtained from the
      culture broth of Trichoderma koningii Oudemans. Primary structures of these
      peptaibols were elucidated by ion-spray ionization mass spectrometry (ISI-MS)
      including the collision-induced dissociation (CID) technique together with two
      dimensional nuclear Overhauser enhancement spectroscopy (NOESY).

PMID- 8536340
TI  - Synthesis and antibacterial activities of optically active substituted 1,2
      dihydro-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids.
AB  - A series of optically active substituted 1,2-dihydro-6-oxo-pyrrolo[3,2,1
      ij]quinoline-5-carboxylic acids was prepared via optically active 2-methyl-4,5
      difluoroindoline (10) and tested for antibacterial activities. Among them, (2S)-9
      [(3R,1'S)-3-(1'-amino)ethyl-1-pyrrolidinyl]-8-fluoro-1,2-dihydro- 2- methyl-6-oxo
      6H-pyrrolo[3,2,1-ij]-quinoline-5-carboxylic acid (19) showed potent activity
      against gram-positive bacteria and (2S)-8-fluoro-1,2-dihydro-2-methyl-9-(3-methyl
      1-piperazinyl)-6-oxo-6H- pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid (16)
      exhibited well balanced in vitro activity, good intravenous efficacy, and high
      aqueous solubility.

PMID- 8536341
TI  - Lactam-conformationally restricted analogs of N alpha-arylsulfonyl arginine
      amide: design, synthesis and inhibitory activity toward thrombin and related
      enzymes.
AB  - Three new lactam-conformationally restricted arginine derivatives, 1-butyl-3-(6,7
      dimethoxy-2-naphthylsulfonyl)-3-(3-guanidinoprop yl)-substituted gamma-, delta-,
      and epsilon-lactams (2-4), were synthesized on the basis of backbone modification
      of the lead structure, 6,7-dimethoxy-2-naphthylsulfonylarginine n
      butylmethylamide (1). We tested these compounds for inhibitory activity toward
      thrombin and other trypsin-like enzymes (trypsin, factor Xa, plasmin, and
      kallikrein). All the compounds synthesized (1-4) potently inhibited thrombin with
      IC50 values of 0.75, 0.70, 0.92, and 3.2 microM, respectively; they inhibited
      thrombin over 40-fold more effectively than the other enzymes tested. The gamma
      lactam (2) with the most profound inhibitory activity toward thrombin was a
      reversible inhibitor with a Ki of 0.26 microM. Compound 2 also showed better
      thrombin selectivity than the lead compound (1). The lactam-conformational
      restriction of arylsulfonylarginine amides, especially gamma-lactam, has thus
      proved to be a useful device for the improvement of antithrombotic activity.

PMID- 8536342
TI  - Thromboxane A2 synthetase inhibitors with histamine H1-blocking activity:
      synthesis and evaluation of a new series of indole derivatives.
AB  - A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid
      derivatives were prepared and evaluated for thromboxane A2 (TXA2) synthetase
      inhibitory and histaminergic H1-blocking activity. Among the compounds
      synthesized, indole-6-carboxylic acid derivatives showed higher activities than
      the other positional isomers of carboxylic acid. 1-[3-(4-Benzhydryl-1
      piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )-1H-indole-6-carboxylic acid (12)
      had the strongest thromboxane synthetase inhibitory activity (IC50 = 5 x 10(-8)
      M) and H1-blocking activity (IC50 = 8 x 10(-9) M).

PMID- 8536343
TI  - Synthesis and antipancreatitis activities of novel N-(2-sulfonylamino-5
      trifluoromethyl-3-pyridyl)carboxamide derivatives as phospholipase A2 inhibitors.
AB  - Novel N-(2-sulfonylamino-5-trifluoromethyl-3-pyridyl)carboxamide derivatives have
      been prepared and evaluated as phospholipase A2 (PLA2) inhibitors. Among these
      compounds, IS-741 (sodium salt of 1j), which showed the highest and the most
      stable therapeutic effect on acute hemorrhagic pancreatitis induced by the closed
      duodenal loop method in rats, was selected as a candidate for further
      development.

PMID- 8536344
TI  - Arylnaphthalene lignans as novel series of hypolipidemic agents raising high
      density lipoprotein level.
AB  - A series of arylnaphthalene lignans were synthesized and tested for hypolipidemic
      activity. The most potent compound (4b) (TA-7552) not only reduced serum
      cholesterol, but also increased high-density lipoproteins cholesterol in rats.
      The effective dose of 4b is 100 times less than that of cholestyramine. Structure
      activity relationships are discussed.

PMID- 8536345
TI  - Synthesis and antitumor activity of novel dolastatin 10 analogs.
AB  - Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10
      analogs each modified at one of the constituent amino acid derivatives, were
      synthesized and their antitumor activity was evaluated against P388 leukemia in
      mice. The structural requirements for antitumor activity are discussed. Some of
      the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly
      active 50c, which lacks the thiazole group of 1, was selected for further
      development as an antitumor agent.

PMID- 8536346
TI  - Studies on agents with vasodilator and beta-blocking activities. III. Synthesis
      and activity of optical isomers of TZC-1370.
AB  - Optical isomers of TZC-1370 (1) were prepared from (R)- and (S)-1-(2
      chlorophenoxy)-2,3-epoxypropane. When given intravenously to anesthetized rats,
      the (S)-isomer was about 40 times more potent in terms of beta-blocking activity
      than the (R)-isomer, while their hypotensive activities were equipotent with that
      of the racemic compound, TZC-1370.

PMID- 8536347
TI  - Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the
      release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets.
AB  - A search for potent inhibitors of release of 12(S)-hydroxyeicosatetraenoic acid
      (12-HETE), which plays an important role in the pathogenesis of various
      circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5
      tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)
      quinolinone derivatives having an azole group in the side chain. Many 2(1H)
      quinolinone derivatives were synthesized and tested in vitro for the inhibitory
      activity in human platelets. 3,4-Dihydro-6-[3-(1-o-tolylimidazol-2
      yl)sulfinylpropoxy]-2( 1H)-quinolinone (5k) was found to be one of the most
      potent inhibitors of 12-HETE release, being more potent than esculetin. In
      addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet
      adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their
      potencies were compared in vitro and in vivo. (S)-(+)-5k had the best
      pharmacological profile and was selected as a candidate drug for further
      development. The structure-activity relationships are discussed.

PMID- 8536348
TI  - Steroidal glycosides from roots of Cynanchum caudatum M. II.
AB  - The roots of Cynanchum caudatum M. (Asclepiadaceae) afforded eleven new pregnane
      glycosides which had cynanchogenin, caudatin, 12-O-benzoyllineolon and 12-O
      benzoyldeacylmetaplexigenin as the aglycone moiety and 2,6-dideoxy-3-O
      methylhexopyranoses as component sugars. The structures of these compounds were
      elucidated by spectroscopic methods and from chemical evidence.

PMID- 8536349
TI  - Release of lidocaine from polymer film dosage forms.
AB  - We investigated the in vitro drug release from mixed polymer films using
      lidocaine (LC), which is poorly water-soluble. The mixed polymer films consisted
      of various ratios of hydroxypropylcellulose (HPC) and
      hydroxypropylmethylcellulose phthalate (HPMCP). The effects of the presence
      glycyrrhizic acid (GL) or polyethylene glycol (PEG) in the films upon LC release
      were also studied. LC crystallinity decreased in the polymer film and this
      decrease was remarkable in the presence of GL, resulting in an amorphous state.
      During the initial stage, drug release was regarded as a zero-order dissolution.
      The apparent release rate constant, ka, varied with the ratios of the two
      polymers and the amount of additives as well as with the pH of the test solution.
      The results indicated that GL enhanced the dissolution rate of LC from mixed
      polymer films, which may be due to the formation of an amorphous state. On the
      other hand, since PEG is a surfactant, the enhanced wettability of the polymer by
      the buffered solutions may have caused the increased dissolution rate.

PMID- 8536350
TI  - Toxicity of dioxins: role of an absolute hardness-absolute electronegativity
      diagram (eta-chi diagram) as a new measure in risk assessment.
AB  - The differences in biological activities among polychlorinated dibenzo-p-dioxins
      (dioxins) are strongly dependent on the substitution pattern of chlorine at
      various positions on the parent dibenzo-p-dioxin molecule. The absolute hardness,
      eta, of dioxins shows a good correlation with the potency of biological activity
      and the chlorine substitution pattern. The result means that the soft dioxins
      have a small HOMO-LUMO gap, and are more toxic than the hard dioxins. Therefore,
      the values of absolute hardness, eta, of dioxins can be used to predict their
      toxic potency (dioxin hardness). Moreover, we show that the absolute hardness
      absolute electronegativity (eta-chi) diagrams, as an activity coordinate, play an
      important role as a new measure in the assessment of the toxicity and potency of
      the biological activity of dioxins.

PMID- 8536351
TI  - Stability constants of Zn(II), Pb(II), Cd(II) and Cu(II) complexes with
      hematoxylin.
AB  - The composition and stability constants of the complexes of Zn(II), Pb(II),
      Cd(II) and Cu(II) with hematoxylin have been studied using direct current
      polarography and differential pulse polarography. The results showed the
      formation of 1:2 (M:L) complexes for Zn(II) and Pb(II), and a 1:6 (M:L) complex
      for Cd(II). However, the formation of copper-hematoxylin complex is irreversible.
      The values of the formation constants for the above complexes at 298, 308 and
      318K were calculated as well as the relevant thermodynamic parameters.

PMID- 8536352
TI  - Water-soluble antitumor agents. I. Synthesis and biological activity of 6-S
      aminoacyloxymethyl mercaptopurine derivatives.
AB  - In an attempt to improve the effectiveness and bioavailability of 6
      mercaptopurine, various kinds of water-soluble analogues, such as 6-S
      aminoacyloxymethyl mercaptopurine derivatives (3a--m) and 6-S,9-disubstituted
      derivates (7a,b and 9a,b), were synthesized. These compounds were evaluated for
      activity to augment antitumor immunity by using a double grated tumor system.
      Antitumor activities against solid tumors (sarcoma 180 and colon 26) were also
      evaluated. Many compounds exhibited potent activities in both test systems. In
      particular, the aminopropionate derivative (3a) and the L-glutamate derivative
      (3f) showed significant enhancement of antitumor immunity together with potent
      antitumor activities.

PMID- 8536353
TI  - Chemical and chemotaxonomical studies on Dicranopteris species.
AB  - Clerodane glycosides and flavonoids in Dicranopteris pedata and three varieties
      of D. linearis were investigated. All the ferns contained a new glycoside,
      (6S,13S)-6-[6-O-acetyl-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopy -
      ranosyloxy]-13-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-fucopyra nosyloxy]-
      cleroda-3,14-diene, as a chemical marker of this group. Flavonoids were limited
      to flavonol 3-O-glycosides. The ferns and isolated flavonoids are as follows; D.
      pedata: afzelin, quercitrin. D. linearis var. brevis: afzelin, quercitrin. D.
      linearis var. tenuis: quercitrin, isoquercitrin. D. linearis var. sebastiana:
      astragarin, isoquercitrin, rutin, kaempferol 3-O-(4-O-p-coumaroyl-3-O-alpha-L
      rhamnopyranosyl)-alpha-L-rhamn opy ranosyl- (1-->6)-beta-D-glucopyranoside.

PMID- 8536354
TI  - Synergists for retinoid in cellular differentiation of human promyelocytic
      leukemia cells HL-60.
AB  - 4-[5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-methyldibenzo[b, e]diazepin-11-yl]benzoic
      acid (4) enhanced the differentiation-inducing activity of retinoic acid (1) and
      of a synthetic retinoid Am80 (2) toward human promyelocytic leukemia cells HL-60,
      although 4 alone did not induce differentiation. The synergistic effect of 4 on
      the activities of retinoids was also seen in suppression of proliferation of HL
      60 cells.

PMID- 8536355
TI  - Breakdown of tolerance to the intestinal bacterial flora in inflammatory bowel
      disease (IBD)

PMID- 8536356
TI  - Tolerance exists towards resident intestinal flora but is broken in active
      inflammatory bowel disease (IBD)
AB  - Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut
      lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness
      against these antigens might be associated with inflammation, we studied the
      immune response to the indigenous intestinal microflora in peripheral blood,
      inflamed and non-inflamed human intestine. Lamina propria monocuclear cells
      (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear
      cells (PBMC) of IBD patients with active inflammatory disease strongly
      proliferated after co-culture with sonicates of bacteria from autologous
      intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb,
      suggesting that it was driven by antigen. LPMC from adjacent non-inflamed
      intestinal areas of the same IBD patients and PBMC or LPMC isolated from non
      inflamed intestine of controls and patients with IBD in remission, in contrast,
      did not proliferate. PBMC or LPMC which had been tolerant to bacteria from
      autologous intestine, however, strongly proliferated after co-culture with
      bacterial sonicates from heterologous intestine (BsH). This proliferation was
      associated with an expansion of CD8+ T cells, increased expression of activation
      markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12,
      interferon-gamma (IFN-gamma), and IL-10 protein. These results show that
      tolerance selectively exists to intestinal flora from autologous but not
      heterologous intestine, and that tolerance is broken in intestinal inflammation.
      This may be an important mechanism for the perpetuation of chronic IBD.

PMID- 8536357
TI  - Peripheral cell-mediated immune response to mycobacterial antigens in
      inflammatory bowel disease.
AB  - A mycobacterial etiology has been proposed in Crohn's disease (CD). We have
      sought evidence of increased or modified T lymphocyte immune responses to
      Mycobacterium tuberculosis and Myco, paratuberculosis in patients with CD (n =
      13), compared with ulcerative colitis (UC; n = 17) and controls (n = 17).
      Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen
      control), mycobacterial purified protein derivative (PPD) preparations, lysates,
      column fractions and whole, heat-killed bacteria. Responses of T cells and T cell
      subsets were assessed by expression of activation markers (CD25, CD69), coupled
      with blastogenesis assays (3H-thymidine uptake) and estimates of proliferation.
      Virtually all patients responded to Myco. paratuberculosis and Myco. tuberculosis
      antigens. There were no significant differences between patient groups, although
      there was a very high overall correlation (r = 0.95; P < 0.0001) between
      responses to the two mycobacterial species. Most of the activation and
      proliferative responses resided in the CD4+ (T helper) subset. Although up to 15%
      of CD8+ (suppressor/cytotoxic) cells also became activated, the CD8+ cells did
      not proliferate subsequently. Cells expressing the alternate gamma delta form of
      the T cell receptor (TCR gamma delta+) did not activate or proliferate in
      response to mycobacterial antigens. There were no differences in any of these
      parameters between patient groups. We conclude that there is no specific increase
      or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel
      disease (IBD). Thus our data do not support a mycobacterial etiopathology of
      Crohn's disease.

PMID- 8536358
TI  - 'Split tolerance' induction by intrathymic injection of acetylcholine receptor in
      a rat model of autoimmune myasthenia gravis; implications for the design of
      specific immunotherapies.
AB  - Experimental autoimmune myasthenia gravis (EAMG) in the Lewis rat, induced by a
      single injection of acetylcholine receptor (AChR) protein, is a model used to
      study human myasthenia gravis (MG). The production of anti-AChR antibodies in the
      animal model and human MG is T cell-dependent, and AChR-specific T cells have
      been considered as a potential target for specific immunotherapy. Intrathymic
      injection of antigens induces antigen-specific tolerance in several T cell
      mediated autoimmune models. We examined the effect of intrathymic injection of
      AChR on T cell responses and the production of antibodies to AChR in EAMG rats.
      Primed lymph node cells from rats receiving intrathymic injection of AChR
      exhibited reduced proliferation to AChR with marked suppression of interferon
      gamma (IFN-gamma) secretion in the antigen-stimulated culture, compared with
      those of rats injected with PBS. However, neither anti-Narke AChR nor anti-rat
      AChR antibody production was suppressed or enhanced in intrathymically AChR
      injected animals compared with that of animals injected intrathymically with PBS
      or perithymically with AChR. This 'split tolerance' may be attributable to the
      suppression of type-1 T helper cells (Th1). Our results suggest that the
      suppression of Th1 function alone may not be sufficient for the prevention of
      antibody-mediated autoimmune diseases.

PMID- 8536359
TI  - Immunotherapy with monoclonal antibodies directed against the immunosuppressive
      domain of p15E inhibits tumour growth.
AB  - Immunosuppressive retrovirus-related proteins, like p15E, are involved in tumour
      associated immunosuppression. In the present study we investigated whether such
      proteins could be used as targets in tumour immunotherapy using MoAbs.
      Immunotherapy was performed in mice inoculated with the Rauscher virus
      transformed myeloid cell line RMB-1. RMB-1 cells express retroviral antigens at
      their cell surface. In order to obtain constant serum titres of MoAbs over a
      prolonged period of time during therapy, anti-p15E antibody-producing hybridoma
      cells were encapsulated in alginate and injected intraperitoneally in tumour
      bearing mice. Using this technique, serum antibody titres of 50-100 micrograms/ml
      were obtained, which remained constant over a period of at least 3 weeks. Therapy
      experiments were performed using anti-p15E antibodies 19F8, which recognizes both
      cell surface-associated as well as circulating p15E, and ER-IS5, which did not
      react with surface-bound p15E beyond background, but which neutralizes
      circulating p15E. Inoculation of alginates containing anti-p15E hybridoma cell
      lines in RMB-1 tumour-bearing mice showed inhibition of tumour cell growth. In
      survival experiments, 19F8 cured eight of 23 tumour-bearing mice. The p15E
      neutralizing antibody ER-IS5 caused a significant longer survival, but therapy
      with this MoAb alone was not sufficient to cure the animals of the RMB-1 tumour.

PMID- 8536360
TI  - Relationships between humoral factors in HIV-1-infected mothers and the
      occurrence of HIV infection in their infants.
AB  - Based on what is known about the biology of HIV-1 vertical transmission, the HIV
      burden of the mother, maternal immune factors and the integrity of the placental
      barrier are likely to play major roles. We therefore sought to determine whether
      the presence of antibodies in sera from 47 HIV-1-infected mothers, including 30
      non-transmitting and 17 transmitting mothers, affected the risk of HIV-1
      transmission to infants. Our findings showed no significant correlation between
      the capacity of antibodies to mediate antibody-dependent cell-mediated
      cytotoxicity (ADCC) and their capacity to induce protection of the child from HIV
      1 infection (P = 0.14). Furthermore, no correlation was found between the
      capacity of maternal antibodies to neutralize in vitro lymphocyte or macrophage
      heterologous viral infection and the occurrence of in vivo HIV-1 infection in the
      infant. Sera recovered from five of 12 transmitting mothers and from five of 11
      non-transmitting mothers were compared in their capacity to neutralize the
      viruses drawn from the same individuals. Four out of five maternal isolates from
      transmitting mothers and all maternal isolates from non-transmitting mothers were
      sensitive to enhancement of infection mediated by the maternal serum.

PMID- 8536361
TI  - Cell cycling in HIV infection: analysis of in vivo activated lymphocytes.
AB  - Infection with HIV results in increased circulating levels of T lymphocytes
      expressing phenotypic markers of immune activation. In the present study, using
      three-colour immunofluorescence, we examined the cell cycle status of these
      activated cells. Activated (HLA-DR+, CD25+ and CD38+) CD4+ and CD8+ T lymphocytes
      in peripheral blood were analysed for DNA content in 15 HIV+ patients and 10
      healthy age- and sex-matched control subjects. As expected, all HIV+ patients had
      elevated percentage levels of activated CD4+ HLA-DR+, CD4+ CD25+, CD8+ HLA-DR+,
      CD8+ CD25+ and CD8+ CD38+ T lymphocytes compared with control subjects (P < 0.001
      for all). Percentage levels of CD4+ HLA-DR+ and CD8+ HLA-DR+T lymphocytes in the
      'proliferative' (S-G2M) phase of the cell cycle were also higher in the HIV+
      patients compared with controls (P < 0.001 for both). The percentage levels of
      proliferative CD4+ CD25+, CD8+ CD25+ and CD8+ CD38+ lymphocytes were, however,
      similar in HIV+ patients and controls, indicating that the proliferative fraction
      of cells in vivo was confined to the HLA-DR+ subset and absent from the CD25+ and
      CD38+ populations. Four HIV+ patients had grossly elevated levels of CD8+
      lymphocytes which were CD38+ (> 95%) and confined to the pre-G0-G1 phase of the
      cell cycle, suggesting these may be cells committed to apoptosis. These
      observations indicate an increase in the proliferative capacity of HLA-DR+ T
      lymphocytes in HIV infection in vivo. The reduced DNA content in other
      populations (e.g. CD38+ CD8+ lymphocytes) of some patients with advanced HIV
      disease suggests that these cells are apoptotic. Thus our results define both
      proliferative and apoptotic processes as a spectrum of activation-related events
      in HIV infection.

PMID- 8536362
TI  - An immunosuppressive murine leukaemia virus induces a Th1-->Th2 switch and
      abrogates the IgM antibody response to sheep erythrocytes by suppressing the
      production of IL-2.
AB  - Many retroviruses have tropism for cells in the immune system and have a
      propensity to induce immunosuppression in the host. Some of the effects of
      retroviruses on immune cell function are thought to be mediated through
      cytokines. Friend ImmunoSuppressive virus-2 (FIS-2) is a low oncogenic murine
      leukaemia virus (MuLV) that induces lymphadenopathy and immunosuppression in NMRI
      mice. The role of T cell cytokines during the generation of a primary antibody
      response in healthy and FIS-2-infected mice was studied following the antibody
      response to sheep erythrocytes by an in vitro immunization (IVI) technique. In
      cultures from FIS-2-infected mice, the antibody response was reduced compared
      with cultures from uninfected mice and the production of the Th2 cytokines IL-4
      and IL-6 was elevated, whereas the Th1 cytokines IL-2, interferon-gamma (IFN
      gamma) and tumour necrosis factor-alpha (TNF-alpha) were reduced. The suppressed
      anti-sheep erythrocyte antibody response in cultures from mice infected with FIS
      2 seemed to be caused by an insufficient production of IL-2, since addition of
      recombinant IL-2 stimulated the antibody response. This effect was also observed
      in cultures depleted of T cells, indicating a direct effect of IL-2 on B cells. A
      switch to a Th2 cell response and suppression of IL-2 production might play a
      central role in the immune cell dysfunction induced by FIS-2.

PMID- 8536363
TI  - Effect of adjuvants on immunization with dengue virus-induced cytotoxic factor.
AB  - Specific active immunization with dengue type 2 virus (DV)-induced cytokine,
      cytotoxic factor (CF), prevents CF-mediated pathology in mice. The present study
      was undertaken to determine the optimum dose of CF and the effect of different
      adjuvants on the immune response as assessed by the study of anti-CF antibody
      titre by ELISA and protection against increase in capillary permeability to
      challenging dose of 3 micrograms CF. The maximum protection of 94 +/- 4% against
      increase in capillary permeability was observed at week 4 after immunization with
      5 micrograms dose of CF mixed with Freund's incomplete adjuvant (FIA), which
      gradually decreased to 21 +/- 10% on week 24. With a dose of 10 micrograms the
      protection obtained was 79 +/- 5%, but persisted for a longer time at a higher
      level. The response was poor with 1 microgram dose of CF. The mean anti-CF
      antibody titres gradually decreased after reaching the peak at week 4 after
      immunization. Mice immunized with different adjuvants emulsified with 5
      micrograms CF were challenged at different intervals with 3 micrograms CF.
      Maximum protection observed with CF + tetanus toxoid (TT) and 84/246 was about 93
      +/- 2% and 97 +/- 2%, while that with alhydrogel was 33 +/- 12% and with bacille
      Calmette-Guerin (BCG) was 67 +/- 4%. At week 24 after immunization, however, the
      best response was obtained with 10 micrograms of adjuvant 84/246. Intracerebral
      challenge with 10 or 100 LD50 dose of dengue type 2 virus showed significantly
      prolonged mean survival time and delayed onset of signs of sickness in immunized
      mice compared with normal mice. The maximum survival time was with adjuvant
      84/246 even at week 24. The findings thus show that the optimum dose of CF is 5
      micrograms and the adjuvant of choice is 84/246.

PMID- 8536364
TI  - Differential alterations in plasma colony-stimulating factor concentrations in
      meningococcaemia.
AB  - To determine whether circulating levels of any of the colony-stimulating factors
      (CSF) might contribute to the host response in severe sepsis, plasma
      concentrations of granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF),
      and macrophage CSF (M-CSF) were measured by immunoassays in 20 subjects with
      meningococcaemia, a bloodstream infection caused by Neisseria meningitidis, that
      has proven to be a valuable model to study the responses of other inflammatory
      mediators during sepsis and septic shock in humans. Plasma G-CSF concentrations
      were transiently elevated in most subjects during the early phase of
      meningococcaemia, and were higher in subjects with septic shock (mean +/- s.d. =
      165 +/- 142 ng/ml, n = 9) compared with those who remained normotensive (mean +/-
      s.d. = 7 +/- 2 ng/ml, n = 10) (P < 0.05). Peak plasma G-CSF concentrations > 10
      ng/ml were associated with the development of septic shock (P < 0.01),
      disseminated intravascular coagulation (P < 0.01), fulminant infection (P <
      0.05), and a fatal outcome (P < 0.01). Plasma GM-CSF concentrations > 1 ng/ml
      were briefly present in subjects with life-threatening septic shock (1-15 ng/ml,
      n = 5), and were strongly associated with fulminant meningococcaemia (P < 0.01).
      Plasma M-CSF concentrations were marginally elevated in all subjects, but were
      not associated with complications related to or arising from sepsis-induced organ
      injury. This study demonstrates that plasma levels of G-CSF, GM-CSF and M-CSF
      show very different responses during meningococcaemia, changes which presumably
      reflect the different roles played by these mediators in sepsis and, potentially,
      in septic shock.

PMID- 8536365
TI  - T cell activation by Theileria annulata-infected macrophages correlates with
      cytokine production.
AB  - A major feature of the pathology induced by Theileria annulata is acute
      lymphocytic proliferation, and this study investigates the mechanisms underlying
      the intrinsic ability of T. annulata-infected monocytes to induce naive
      autologous T cells to proliferate. Different T. annulata-infected clones
      expressed different but constant levels of MHC class II, varying from < 1.0 x
      10(5) to 1.5 x 10(6) molecules/cell, as measured by saturation binding. However,
      no correlation was found between the level of MHC class II expression and levels
      of induced T cell proliferation. Theileria annulata-infected cell lines and
      clones were assayed for cytokine mRNA expression by reverse transcription
      polymerase chain reaction (RT-PCR). The infected cells assayed produced mRNA
      specific for IL-1 alpha, IL-1 beta, IL-6, IL-10 and tumour necrosis factor-alpha
      (TNF-alpha), but not IL-2 or IL-4. One clone (clone G) did not produce mRNA for
      TNF-alpha. The degree of T cell proliferation induced by infected cells was
      directly correlated with the amount of mRNA produced for the T cell stimulatory
      cytokines IL-1 alpha and IL-6, as assessed by a semiquantitative technique. In
      contrast, cells infected with the related parasite T. parva produced mRNA for IL
      1 alpha, IL-2, IL-4, IL-10 and interferon-gamma (IFN-gamma). Since T. parva
      infected cells also induce naive autologous T cell proliferation, it seems likely
      that the production of IL-1 alpha by cells infected with either parasite is a
      major signal for the induction of non-specific T cell proliferation.

PMID- 8536366
TI  - Phenotypic characterization of two cell populations involved in the acquisition
      of suppressor activity by cultured spleen cells from Mycobacterium lepraemurium
      infected mice.
AB  - The impairment of cellular immunity in mice infected with Mycobacterium
      lepraemurium was shown to correlate with the development of suppressor cells. We
      have previously reported that before suppressor activity is detectable in freshly
      harvested cell suspensions, suppressor cell precursors accumulate in the spleen
      of infected mice. Upon overnight culture in the presence of a regulatory cell
      subset, these precursor cells acquire the capacity to impair the concanavalin A
      (Con A)-induced proliferation of normal spleen cells. The purpose of this study
      was to determine the phenotype of the cells involved in this phenomenon. This was
      done by following the development of suppressor activity in spleen cell
      suspensions depleted of defined cell subsets of the adherent or the non-adherent
      cell fractions with selected MoAbs and immunomagnetic beads or by in vivo
      treatment. Our results indicate that the acquisition of suppressor activity
      requires the interaction of Ia+CD11b+Fc gamma R+IgG- asialo GM1- adherent cells
      with Thy1-CD4-CD8-IgG-Ia- asialo GM1-Fc gamma R+CD11b+ non-adherent cells. It is
      also shown that the development of suppressor activity is impaired by preventing
      cell-cell contact between these two cell subsets through coculture in 'Transwell
      chambers'. These observations support the conclusion that the in vitro
      acquisition of suppressor activity is a consequence of the maturation of
      suppressor cell precursors of the monocytic lineage induced by a receptor-ligand
      type interaction with a non-adherent cell subset that is clearly distinct from
      mature T, B and natural killer (NK) cells.

PMID- 8536367
TI  - Immune responsiveness in Mycobacterium avium-infected mice: changes in the
      proportion of T cell subsets and antibody production during the course of
      infection.
AB  - The C57Bl/6 susceptible (Bcgs) and its resistant (Bcgr) congenic mouse,
      previously developed by retrogressive backcrossing, were infected with 1 x 10(6)
      colony-forming units (CFU) of Mycobacterium avium and bacterial growth and their
      immune responses during the early and prolonged periods of infection were
      examined. There was a high proliferation in the liver and spleen of Bcgs mice,
      whereas no proliferation was observed in the Bcgr mice. Similarly, the sizes and
      weights of these organs were much higher than those of their Bcgr counterparts.
      The size and number of granulomas in Bcgs were also found to be higher than those
      of Bcgr. The CD3+ and CD4+ subsets increased dramatically in both mice during the
      early stage of infection. However, in the later phase of the infection, these
      populations decreased dramatically in Bcgs mice, but not in Bcgr mice, resulting
      in a depression in cell-mediated immune responses. No significant decrease in
      cell-mediated immune responses was observed in Bcgr mice even after prolonged
      infection. ELISA was performed to determine the antibody levels in both mice, and
      it was found that serum IgG and IgM levels in Bcgs were comparatively higher than
      those in Bcgr mice throughout the period of infection. The Bcg gene therefore may
      have an important role in the maintenance of resistance not only in the early
      phase but also in the later phase of Myco. avium infection.

PMID- 8536368
TI  - Anti-malaria antibody-producing B cell frequencies in adults after a Plasmodium
      falciparum outbreak in Madagascar.
AB  - The central highlands of Madagascar offer a unique opportunity to explore the
      malaria immune memory, as the last murderous epidemic in the study area occurred
      8 years ago. Quantification of the circulating memory B lymphocytes reacting to
      Plasmodium falciparum was assessed among 14 Madagascans by using a limiting
      dilution assay, applied to the EL4 culture system, which leads to activation,
      proliferation and differentiation into antibody-secreting cells (ASC) of most
      peripheral B cells. This system allowed us to observe, without any malaria
      specific restimulation, a geometric mean frequency of one anti-P. falciparum ASC
      among 2992 circulating B cells, except for one Madagascan who did not have any
      detectable ASC. A geometric mean frequency of one anti-P. falciparum ASC among
      1403 was obtained for six malaria hyperimmune Cameroonians, but conversely, no
      anti-malaria ASC was detected in the blood of six malaria non-immune French
      control subjects. Anti-P. falciparum ASC frequencies and serum specific
      antibodies were strongly related. Our results indicate that anti-malaria ASC are
      still present in peripheral blood of Madagascan subjects, who have not been
      exposed to P. falciparum for several years. These responder B cells reflect the
      malaria B cell memory acquired during the last epidemic.

PMID- 8536369
TI  - Serum soluble markers in the evaluation of treatment in human visceral
      leishmaniasis.
AB  - Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery
      from VL is linked to cellular immune response. Unresponsiveness to antimonial
      therapy reinforces the importance of determining parameters for treatment
      assessment. We analysed the pre- and post-treatment serum levels of soluble CD4
      (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and
      neopterin in groups of VL patients either responsive or not to standard
      antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1
      were significantly higher in VL patients than in healthy subjects from the same
      area (P < 0.05). sICAM-1 levels were similar in healthy controls and in VL
      patients refractory to antimonial therapy (P = 0.25), but significantly higher in
      patients responsive to treatment (P = 0.02). The comparison of pre- and post
      treatment concentrations showed that all markers, except sCD4 and sICAM-1,
      presented a significant fall (P < 0.05) in patients responsive to antimonial
      therapy. However, only neopterin presented with levels compatible with those of
      healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM
      1 presented with post-treatment levels significantly higher than the pretreatment
      determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01).
      All markers displayed clearly distinct behaviour according to the patient's
      response to therapy. This makes all soluble molecules studied suitable for use as
      indicators of antimonial therapy response. Additionally the comparison of
      pretreatment levels of the markers between responders and refractory patients to
      antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1
      significantly differed among these two groups (P = 0.02 in each case), suggesting
      that they may be used in future as predictors of antimonial therapy response.

PMID- 8536370
TI  - Changes in the phenotype of monocytes/macrophages and expression of cytokine mRNA
      in peripheral blood and synovial fluid of patients with rheumatoid arthritis.
AB  - Data from a previous study suggested that peripheral blood monocytes in patients
      with rheumatoid arthritis (RA) may be activated. Therefore, in this study we
      sought further evidence of 'presynovial' activation of monocytes. Our results
      show that phenotypic changes are demonstrable in peripheral blood monocytes in
      patients with RA, including increased expression of CR3 (CD11b/CD18) and FcRI
      (CD64). However, changes are most extensive in synovial monocytes/macrophages and
      especially for HLA-DR and intercellular adhesion molecule-1 (ICAM-1) (CD54). We
      conclude that monocyte/macrophage activation is most evident within the joint,
      and that 'presynovial' changes occur but are of limited extent.

PMID- 8536371
TI  - High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are
      expression of CD30+ T cell involvement in the inflamed joints.
AB  - The CD30 is a surface molecule expressed by Th2-type lymphokine-producing T cells
      upon activation. CD30-expressing activated T cells release a soluble form of the
      molecule, which can be detectable both in vitro and in vivo. In the present
      study, high levels of soluble CD30 were found in peripheral blood and synovial
      fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were
      significantly present in synovial fluid, but not in peripheral blood, of RA
      patients. Serum values of soluble CD30 were higher in active than inactive RA
      patients and directly correlated with rheumatoid factor serum titres. These data
      strongly support an involvement of CD30+ T cells in the immune processes of
      rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine
      secreting T cells and the pathological response in RA.

PMID- 8536372
TI  - Reactive arthritis-associated bacteria can stimulate lymphocyte proliferation in
      non-exposed individuals and newborns.
AB  - In reactive arthritis (ReA) a specific T cell response to the triggering
      bacterial antigen is present in the synovial fluid, while in paired peripheral
      blood T cells the response is markedly reduced. The proliferative response to ReA
      associated bacteria in the peripheral blood of ReA patients was compared with
      that seen in the blood of healthy adults, who denied exposure to these microbes,
      and in the umbilical cord blood of newborns, who have clearly not been exposed to
      bacterial antigen. Peripheral blood mononuclear cells (PBMC) from non-exposed
      adults and those from umbilical cord blood proliferated to ReA-associated
      bacteria, whilst little response was seen in ReA PBMC. The response was MHC class
      II-restricted, required processing of the bacterial antigen, was seen in both
      CD45RO+ and CD45RA+ subsets, and was not oligoclonal. These T cell responses are
      similar to those previously demonstrated in non-exposed individuals to malaria,
      leishmania and trypanosoma antigen, and may reflect the existence of 'natural' T
      cell immunity to ReA-associated bacteria. The lack of such responses in ReA
      peripheral blood may suggest that such 'natural' responses may restrict the
      dissemination or progression of infection.

PMID- 8536373
TI  - Differential effects of methotrexate and liposomally conjugated methotrexate in
      rat adjuvant-induced arthritis.
AB  - In this study we evaluated the comparative efficacy of free and liposomally
      conjugated methotrexate on both disease induction and suppression of acute
      inflammation in rat adjuvant-induced arthritis. Rats were given either empty
      liposomes (E-LIPO), free methotrexate (MTX) or the liposomally conjugated
      methotrexate (MTX-LIPO) at a dose of 100 micrograms/day for 7 consecutive days by
      the intravenous route. When MTX treatment was initiated on the day of arthritis
      induction the drug suppressed but did not abolish the development of joint
      inflammation. Free MTX had no significant anti-inflammatory effect upon an
      established arthritis when dosing was commenced on day 11 post-adjuvant
      induction. Conversely, MTX-LIPO did not affect the progression of the arthritis
      when dosing was started on day 0, but exerted a significant anti-inflammatory
      effect on an established arthritis. MTX-LIPO treatment was significantly less
      haematotoxic than free MTX.

PMID- 8536374
TI  - Molecular characteristics of anti-self antibody fragments against neutrophil
      cytoplasmic antigens from human V gene phage display libraries.
AB  - Recently it has been demonstrated that human antibody fragments with binding
      activities against self antigens can be isolated from repertoires of rearranged V
      genes from non-immunized humans. We have applied phage display technology to
      study the B cell repertoire for antibody activity against neutrophil cytoplasmic
      antigens. These antibodies may play an important role in Wegener's granulomatosis
      (WG) and related forms of vasculitides. Autoantibodies in patients with WG are
      directed against proteinase 3. The immunodominant antigen in other forms of
      vasculitis is myeloperoxidase, but the B cell response can also be directed
      against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase,
      lactoferrin and cathepsin G. We show here that anti-self reactivity against
      neutrophil cytoplasmic antigens can be detected in the rearranged V gene
      repertoire of healthy individuals and that the reactivity can be directed against
      structural related epitopes which are present on different neutrophil cytoplasmic
      antigens. The scFv with binding activities were sequenced and the V gene usage,
      the level of somatic mutations and the immunoserological characteristics of the
      antibody fragments are discussed. Further evidence is presented that antibody
      fragments consisting only of a heavy chain variable domain can recognize
      neutrophil cytoplasmic antigens in a specific manner. These single-domain
      antibody fragments were used in experiments designed to establish the relative
      role of the light chain variable domains in antigen binding.

PMID- 8536376
TI  - A component of the medicinal herb ephedra blocks activation in the classical and
      alternative pathways of complement.
AB  - Extracts of the herb Ephedra sinica have long been used in traditional Chinese
      medicine for the treatment of, among other conditions, acute nephritis. In
      preliminary studies it was shown that extracts of ephedra caused inhibition of
      complement in vitro. We thus set out to isolate the active component(s) of this
      herb, to examine the complement-inhibiting capacity in sera from different
      species, and to characterize the mechanism(s) by which it inhibits complement.
      Aqueous extraction of the herb followed by fractionation using thin layer
      chromatography (TLC) demonstrated that complement-inhibiting activity resided
      within a single band, hereafter termed the complement-inhibiting component (CIC),
      which represents an as yet uncharacterized polyanionic carbohydrate molecule. TLC
      purified CIC inhibited the classical complement pathway in all species tested
      (human, pig, guinea pig, rat and rabbit). Using erythrocyte intermediates and
      sera specifically depleted of individual components it was apparent that CIC
      inhibited C2. This finding was confirmed using purified human C2, CIC causing a
      dose-dependent loss of C2 haemolytic activity. At much higher doses, CIC also
      showed some inhibiting effect in the terminal pathway, and this was shown to be
      due to inhibition of C9. In the alternative pathway CIC also showed inhibitory
      activity, although its site of action in this pathway remains unresolved. In
      Chinese medicine the herb is taken orally, though no studies of complement levels
      in patients taking the herb have been reported. Preliminary data indicate that
      oral administration in rats causes a partial inhibition of serum complement
      activity. Given the current enthusiasm for complement inhibition as a therapy for
      inflammatory diseases, this non-toxic, naturally occurring agent might be of
      therapeutic value.

PMID- 8536375
TI  - Complement activation by malignant B cells from patients with chronic lymphocytic
      leukaemia (CLL).
AB  - It has previously been reported that the expression of the complement receptors
      CR1 (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with
      the expression on normal B cells, while deposition of complement C3 fragments, as
      a consequence of alternative pathway (AP) activation of complement, is observed
      on mononuclear cells from patients with B CLL. Following our demonstration that
      normal B cells are capable of activating the AP of complement in a CR2-dependent
      fashion, we have chosen to re-examine the complement-activating ability of B CLL
      cells in relation to their altered phenotype with respect to CR2 and the
      complement regulatory membrane proteins, CR1, decay accelerating factor (DAF)
      (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to
      measure expression of complement receptors and regulatory proteins on CD5+ B
      cells from CLL patients, as well as the deposition of C3 fragments occurring both
      in vivo and after in vitro AP activation. We have confirmed the reduced
      expression of CR1 and CR2 on CLL cells and have shown that AP activation in the
      presence of homologous, normal serum was reduced on B CLL cells compared with
      normal B cells. The degree of AP activation correlated directly with CR2
      expression. In addition, we observed that CLL cells bear in vivo-deposited C3d,g,
      although at a significantly lower level than normal B cells.

PMID- 8536377
TI  - Functional activity of the membrane-associated complement inhibitor CD59 in a pig
      to-human in vitro model for hyperacute xenograft rejection.
AB  - Hyperacute rejection triggered by activation of the recipient's complement system
      represents the major barrier to successful xenotransplantation. Transfer of human
      membrane-associated complement regulators to donor organs has been suggested as
      one strategy to interfere with complement-mediated hyperacute xenograft
      rejection. Pigs are discussed as potential organ donors. We therefore
      investigated a putative protective function of the membrane-bound complement
      inhibitor CD59 in a pig-to-human in vitro model of hyperacute xenograft
      rejection. Aortic porcine endothelial cells were transfected with human CD59
      cDNA. Expression of human CD59 was demonstrated by cytofluorimetric and RNA
      analysis. Removal of CD59 from the cell surface by phosphatidylinositol-specific
      phospholipase C (PI-PLC) demonstrated its production as a glycosyl
      phosphatidylinositol (GPI)-anchored protein. Functional activity of the
      transfected CD59 was tested by a lactate dehydrogenase (LDH) release assay for
      complement-mediated lysis. Porcine endothelial cells expressing human CD59 were
      significantly protected from lysis by human serum complement compared with CD59-
      cells. The protective effect was abolished by preincubating the cells with anti
      CD59 antibodies or PI-PLC. We calculated by Scatchard analysis that the
      established CD59+ cell line expressed a CD59 level comparable to that of human
      endothelial cells. Our results recommend the production of pigs transgenic for
      CD59.

PMID- 8536378
TI  - Increased expression of proopiomelanocortin (POMC) mRNA in adrenal glands of mice
      undergoing graft-versus-host disease (GVHD): association with persistent elevated
      plasma corticosterone levels.
AB  - GVHD in animal models induces severe thymic atrophy as a result of prolonged
      secretion of high concentrations of adrenal glucocorticoids. In this study we
      investigated the mechanism responsible for the persistent stimulation of the
      adrenal glands to secrete glucocorticoids in mice undergoing GVHD. GVHD was
      induced across the major and multiple minor histocompatibility antigen difference
      in unirradiated C57Bl/6 x AF1 hybrid mice by the intravenous injection of A
      strain parental lymphoid cells. Our results showed plasma corticosterone (CS)
      levels were elevated in association with high concentrations of corticotropin
      (ACTH) in both the GVHD and control syngeneic (SYN) groups on day 9. By days 16
      and 24, plasma CS and ACTH in the SYN mice returned to basal levels. In contrast,
      plasma CS levels remained elevated in the GVHD animals on days 16 and 24 despite
      decreasing concentrations of plasma ACTH. Reverse transcription-polymerase chain
      reaction (RT-PCR) showed several-fold increase in POMC mRNA in the adrenal glands
      of GVHD mice compared with SYN animals. In addition, high mRNA levels for murine
      prohormone convertase 1, the enzyme that cleaves POMC into ACTH, were also
      detected in GVHD adrenals. Histological analysis of GVHD adrenals failed to show
      any sign of adrenalitis, and RT-PCR of GVHD adrenals also failed to detect mRNA
      for interferon-gamma (IFN-gamma), a cytokine expressed by activated T and natural
      killer (NK) cells. However, mRNA for IL-12, a cytokine produced by activated
      macrophages, was increased in GVHD adrenals, suggesting that resident adrenal
      macrophages were activated during GVHD. Our findings suggest that persistent
      elevated levels of plasma glucocorticoids during GVHD could be mediated by intra
      adrenal ACTH produced by resident adrenal macrophages activated as a consequence
      of GVHD.

PMID- 8536379
TI  - Decreased release of IL-10 by monocytes from patients with lipoid nephrosis.
AB  - IL-10, a cross-regulatory cytokine produced by several cell types, including
      monocytes, is known to stimulate B cell growth and maturation and to inhibit
      cytokine production. In order to characterize further monocyte function in
      patients with lipoid nephrosis (LN), the release of IL-10 was measured in
      supernatants of cultured peripheral blood monocytes (PBM) that were obtained from
      LN patients and healthy controls. Spontaneous and lipopolysaccharide (LPS)
      induced IL-10 release was decreased in patients with LN compared with those in
      normal controls and lower in LN patients with the nephrotic syndrome (NS) than in
      those without NS. In contrast, the values in IgA nephropathy (IgAN) patients with
      or without NS did not differ from normal subjects. There was a negative
      correlation between IL-10 concentration and the quantity of vascular permeability
      factor (VPF) released in LN patients. These imply that there is a relative
      deficit in IL-10 release in active LN, which suggests the possibility that
      inadequate release of IL-10 may lead to increased VPF activity in active LN
      patients and the measurements of IL-10 may be of value for monitoring kidney
      disease. The data provide the first detailed analysis of IL-10 in a group of
      patients with LN.

PMID- 8536380
TI  - Cyclosporin A (CsA) modulates the glomerular production of inflammatory mediators
      and proteoglycans in experimental nephrosis.
AB  - Nephrosis is characterized by glomerular epithelial cell injury and a decrease in
      the glomerular basement membrane (GBM) proteoglycan content. Although CsA is a
      useful treatment for a group of patients with this disease, its mechanism of
      action is unclear. We have previously shown that in experimental nephrosis there
      is an increase in the glomerular production of tumour necrosis factor-alpha (TNF
      alpha) and platelet-activating factor (PAF). Here we have studied the effect of
      CsA on kidney generation of TNF-alpha and PAF in puromycin aminonucleoside (PAN)
      nephrosis as well as on the synthesis of proteoglycans by cultured glomerular
      epithelial cells. Rats receiving CsA had, on day 8 of PAN injection, a
      significant reduction in proteinuria, blood cholesterol levels and in
      interstitial mononuclear cells. A diminution in glomerular production and urinary
      excretion of TNF-alpha and PAF was also noted. In in vitro studies, at 24 h of
      incubation PAF and TNF-alpha induced in glomerular epithelial cells a significant
      decrease in proteoglycan synthesis. Neither PAF nor TNF-alpha had any significant
      effect on glomerular epithelial cell proliferation. CsA alone induced a dose
      response increase in proteoglycan synthesis and a slight decrease in cell
      proliferation. CsA also reversed the inhibitory effect of PAF and TNF-alpha on
      proteoglycan synthesis. However, CsA did not alter the pattern of proteoglycan
      production, remaining around 50% chondroitinase ABC-, 15% heparitinase-sensitive.
      Our results indicate that PAF and TNF-alpha could be implicated in the
      pathogenesis of nephrosis through the inhibition of proteoglycan synthesis by
      glomerular epithelial cells. The beneficial effect of CsA in nephrosis may be due
      to the recovery of the GBM charge selectivity caused by the normalization of
      glomerular PAF and TNF-alpha synthesis and the increase in proteoglycan synthesis
      by glomerular epithelial cells.

PMID- 8536381
TI  - Antigen processing and presentation by a murine myoblast cell line.
AB  - The ability of non-professional antigen-presenting cells (APC) to process and
      present antigen to the immune system has been the subject of debate in
      autoimmunity and tumour immunology. The role of muscle cells in the processing
      and presentation of antigen to T cells via class I and class II MHC pathways is
      of increasing interest. Muscle cells are the targets of autoimmune attack in the
      inflammatory muscle diseases, and direct intramuscular injection of antigen
      expressing DNA constructs is under scrutiny as a means of vaccination.
      Furthermore, the immunological properties of muscle cells are of relevance in
      attempts to transfer myoblasts as replacement cells in dystrophic diseases or as
      depot cells for the secretion of certain molecules in deficiency states. Using
      class I and class II MHC transfectant clones of the C2C12 myoblast cell line,
      myoblasts have been shown to be capable of presenting antigen to, and stimulating
      secretion of IL-2 by, T cell hybridomas via both of these pathways. The epitopes
      which are dominantly presented by professional APC after processing of native
      antigens were also presented by the myoblast cell line after processing of either
      ovalbumin (class I) or hen egg lysozyme (class II). Further, antigen processing
      and presentation via the class II pathway were enhanced by pretreatment of the
      myoblasts with interferon-gamma (IFN-gamma). Up-regulation of invariant chain
      expression by this treatment may have contributed to this enhanced presentation,
      but an effect of IFN-gamma on the expression of other molecules such as H-2 DM
      may have also played a role. The demonstration of the antigen-presenting
      properties of these myoblasts is of relevance to all three areas mentioned above.
      In each situation myoblasts comprise a significant population within muscle. In
      the case of inflammatory muscle diseases the process of muscle degeneration and
      regeneration is on-going, while in the vaccination procedure some muscle damage
      occurs, and vaccination is more effective when muscle damage has preceded
      inoculation.

PMID- 8536382
TI  - Recombinant soluble Fc gamma RII inhibits immune complex precipitation.
AB  - Control of IgG immune complex formation and deposition is important in
      determining the nature and extent of subsequent immune effector responses, and
      appears to be aberrant in some autoimmune diseases. In this study we demonstrate
      that recombinant soluble Fc gamma RII (rsFc gamma RII) is an effective modulator
      of immune complex formation, delaying immune precipitation in a manner which is
      dose-dependent, and can be specifically inhibited by anti-Fc gamma RII MoAb Fab'
      fragments. This inhibitory role in immune precipitation also provides a possible
      mechanistic explanation for our previous demonstration of the efficacy of rsFc
      gamma RII as an inhibitor of immune complex-induced inflammation in the Arthus
      reaction in vivo. RsFc gamma RII inhibited immune complex precipitation in two
      different experimental systems. First, rsFc gamma RII inhibited the precipitation
      of 125I-bovine serum albumin (BSA)-anti-BSA complexes in a dose-dependent manner,
      while an irrelevant protein (soybean trypsin inhibitor) had no effect on the
      precipitation of the immune complexes. Moreover, rsFc gamma RII inhibited the
      precipitation of ovalbumin (OVA)-anti-OVA complexes as determined by
      turbidimetric analysis, where the inhibition of immune complex precipitation by
      rsFc gamma RII was dose-dependent and was specifically blocked by prior
      incubation with Fab' fragments of a blocking MoAb to Fc gamma RII. RsFc gamma RII
      could inhibit the precipitation of BSA-anti-BSA complexes in the presence of
      excess bystander IgG and did not inhibit complement-mediated prevention of immune
      precipitation, demonstrating that rsFc gamma RII did not block C1 binding to the
      BSA-anti-BSA complex. Unlike complement, rsFc gamma RII could not cause re
      solubilization of pre-formed precipitated BSA-anti-BSA complexes. Soluble Fc
      gamma Rs have been detected in biological fluids of normal and inflammatory
      disease patients, yet the role of sFc gamma R is still unclear. However, they now
      play a potential role in the modulation of immune complex solubility.

PMID- 8536383
TI  - Serological distinction of integral plasma membrane proteins as a class of
      mycobacterial antigens and their relevance for human T cell activation.
AB  - This study pertains to classification and antigenic analysis of mycobacterial
      plasma membrane proteins in relation to human T cell proliferative responses,
      using a 'fast grower' Mycobacterium fortuitum as model. Membrane vesicles,
      prepared by sonication and differential centrifugation, were subjected to
      biphasic Triton X-114 extraction for isolation of integral peripheral (aqueous
      phase) proteins. Neither protein pool showed any appreciable overlap
      serologically. SDS-PAGE showed five prominent bands in peripheral and three in
      the integral protein pool, whereas immunoblotting with rabbit antisera identified
      only two major antigens (60 and 67 kD) in the former and five (24, 34, 42, 51 and
      54 kD) in the latter. ELISA with a panel of anti-mycobacterial MoAbs revealed
      that nine out of 12 previously known antigens were present in the peripheral
      protein pool. Only two of them (33 and 40 kD) were additionally detected amongst
      integral proteins. The membrane-associated immunosuppressive moiety
      lipoarabinomannan was semiquantitatively located in aqueous phase. In bulk T cell
      proliferation assays, seven out of 10 subjects belonging to a 'responder'
      background (BT-BB leprosy patients and healthy contacts) showed high responses
      for Myco. fortuitum antigens. Proliferative response with integral proteins was
      comparable to that with whole membrane, but it was significantly higher (P <
      0.0005) than the response with peripheral proteins. The distinction and relevance
      of integral membrane proteins as a class of mycobacterial antigens make them
      worthy of consideration in a subunit vaccine design.

PMID- 8536384
TI  - The influence of tetracyclines on T cell activation.
AB  - Minocycline has been shown to have an anti-inflammatory effect in patients with
      rheumatoid arthritis (RA). Since there is evidence that RA is a T cell-mediated
      disease, we investigated the effect of minocycline on human T cell clones derived
      from the synovium of an RA patient. The T cells, when activated via the T cell
      receptor (TCR)/CD3 complex, were suppressed functionally by minocycline,
      resulting in a dose-dependent inhibition of T cell proliferation and reduction in
      production of IL-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha
      (TNF-alpha). Besides an inhibition of IL-2 production, minocycline exerted its
      effect on T cell proliferation by induction of a decreased IL-2 responsiveness.
      We showed that the chelating capacity of minocycline plays a crucial role in the
      inhibitory effect on T cell function, since the inhibitory effect on T cell
      proliferation could be annulled by addition of exogenous Ca2+. However,
      minocycline did not markedly influence the typical TCR/CD3-induced intracellular
      Ca2+ mobilization. Taken together, the results clearly indicate that minocycline
      has immunomodulating effects on human T cells.

PMID- 8536385
TI  - Isolation and functional characterization of T cells from human sputum.
AB  - T cells play a central role in the control of inflammation in the bronchial
      mucosa through the elaboration of proinflammatory cytokines. This study describes
      a method for the isolation and cloning of T cells from sputum of adult subjects.
      In sputum, T cells were of a minor population (< 2% of total cells), and not all
      expressed activation markers for CD29 (very late antigen-1 (VLA-1)), IL-2R and
      HLA-DR. When cultured in the presence of rIL-2 for 7 days and then cloned by
      limiting dilution, the ratios of CD4+ and CD8+ T cell clones (TCC) generated
      reflected those of CD4+ and CD8+ T cells found in sputum. CD4+ TCC and primary
      CD4+ T cell populations produced a range of proinflammatory cytokines when
      stimulated with immobilized anti-CD3 MoAb. Analysis of mRNA messages by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and Southern blot showed good
      correlation with the production of cytokine in culture supernatants. A
      correlation existed between the pattern of cell infiltrate in sputum and the
      cytokine profile.

PMID- 8536386
TI  - Mannose-binding protein in preterm infants: developmental profile and clinical
      significance.
AB  - The aim of this study was to determine the developmental profile of mannose
      binding protein (MBP) in preterm infants. MBP was measured in 885 longitudinally
      collected serum samples from 168 preterm infants, and 63 were genotyped with
      respect to the codon 54 mutation in the MBP gene. MBP level/codon 54 genotyping
      were also determined on the cord blood of 146/123 term infants and 138/123
      adults, respectively. The best cut-off values of MBP for dividing preterm, term
      infants and adults into 'low' and 'high' MBP groups were 400 ng/ml (55 low, 113
      high), 700 ng/ml (35 low, 111 high) and 750 ng/ml (33 low, 105 high),
      respectively, by achieving the least number of misclassifications according to
      the codon 54 mutation. The relative risk of the 'low' groups for presence of the
      codon 54 mutation compared with 'high' groups were 42.4, 67.9 and 22.9 for
      preterm, term infants and adults, respectively (P < 0.00001). The gestational age
      and birth weight of the 'low' (n = 55) and 'high' (n = 113) MBP groups of the 168
      preterm infants were 29.5 +/- 2.8 weeks, 30.5 +/- 2.8 weeks (P = 0.03) and 1230
      +/- 317 g, 1277 +/- 289 g (P = 0.35), respectively. The mean MBP levels of these
      two groups of preterm infants were different (P < 0.001) at all ages measured. As
      a whole group, the MBP level rose from a mean of 500 ng/ml at 25 weeks gestation
      to 1700 ng/ml at 20 weeks post full-term. The mortality rates of 'low' and 'high'
      MBP groups of preterm infants were 22% and 12%, respectively (P = 0.113). This
      difference in mortality was due to gestational age and birth weight standard
      deviation score (SDS) after adjusting for length of gestation and gender (P =
      0.0001) rather than to low MBP levels (P = 0.65). MBP levels were not related to
      birthweight SDS score (P = 0.26). The mean +/- s.d. MBP levels for preterm, term
      infants and adults without the codon 54 mutation were 1225 +/- 701 ng/ml (n =
      45), 2064 +/- 829 ng/ml (n = 88) and 2473 +/- 1395 ng/ml (n = 95), respectively;
      the corresponding values for those with the codon 54 mutation were 130 +/- 275
      ng/ml (n = 18), 533 +/- 665 ng/ml (n = 35) and 330 +/- 225 ng/ml (n = 28),
      respectively. Intra-uterine growth retardation in preterm infants does not
      influence MBP levels. For those without the codon 54 mutation, there is a
      significant difference in MBP level between the three age groups. For those with
      the codon 54 mutation, there is a significant difference between preterm and term
      infants, but not between term infants and adults. We conclude that there is a
      maturation in MBP levels for preterm infants, and that a moderately low MBP
      phenotype does not affect survival. We cannot exclude an effect of profoundly
      reduced MBP levels (characteristic of individuals homozygous for the codon 54
      mutation), since no such preterm infant was identified in this study.

PMID- 8536387
TI  - Exposure to hyperbaric oxygen induces tumour necrosis factor-alpha (TNF-alpha)
      secretion from rat macrophages.
AB  - We investigated the secretion of TNF-alpha by monocytes and macrophages derived
      from the peripheral blood, spleen, and lungs after a single exposure to a
      therapeutic profile of hyperbaric oxygen (HBO). Rats were exposed for 90 min to
      either 100% oxygen at 0.28 MPa (2.8 atmospheres absolute) or air. Immediately
      after exposure, mononuclear cells were isolated from blood, spleen, and lungs and
      cultured for 18 h. The secretion of TNF-alpha from the cultured
      monocytes/macrophages was determined with and without stimulation with
      lipopolysaccharide (LPS). Exposure to hyperbaric oxygen induced a significant
      increase in the spontaneous ex vivo secretion of TNF-alpha (without LPS) by
      mononuclear cells from the blood, spleen, and lung (P < 0.05 from air controls).
      Stimulation with LPS after exposure to HBO induced a significant increase in TNF
      alpha secretion by lung and spleen macrophages compared with air controls (P <
      0.05). However, absolute TNF-alpha levels were not significantly higher than
      those achieved 'spontaneously' in macrophages exposed to HBO without LPS.
      Stimulation with LPS induced a marked increase in secretion of TNF-alpha from
      blood monocytes after exposure to air, but not after exposure to HBO. These
      results provide evidence in support of a role played by TNF-alpha in mediating
      HBO effects on different tissues and their immune responses.

PMID- 8536388
TI  - Clinical audit: don't look a gift horse in the mouth.

PMID- 8536389
TI  - Nothing succeeds like success--some do's and don'ts in clinical audit.

PMID- 8536390
TI  - Imaging carotid stenosis.

PMID- 8536391
TI  - Imaging children with ambiguous genitalia and intersex states.

PMID- 8536392
TI  - Does the angiographic appearance of a carotid stenosis predict the risk of stroke
      independently of the degree of stenosis?
AB  - We aimed to determine whether the angiographic characteristics of recently
      symptomatic carotid stenosis predict risk of subsequent ischaemic stroke
      independently of the degree of stenosis. First, two observers compared the
      angiographic characteristics of patients who subsequently suffered a carotid
      distribution ischaemic stroke ipsilateral to the stenosis (n = 50) with those of
      stroke-free controls (n = 100) matched for the degree of stenosis of the
      symptomatic internal carotid artery. No significant differences were found.
      Secondly, seven independent observers attempted to identify the angiograms of 50
      patients who subsequently suffered a stroke from those of 50 stroke-free controls
      matched for degree of stenosis, age and sex. None of the observers identified the
      stroke case more often than was expected by chance alone. We conclude that
      clinicians cannot differentiate between 'high risk' and 'low risk' carotid
      stenoses on the basis of angiographic characteristics other than the degree of
      stenosis.

PMID- 8536393
TI  - Abdominal aortic injury associated with transverse lumbar spine fracture--imaging
      findings.
AB  - The association of abdominal aortic injury with transverse fractures of the
      lumbar spine is not well recognized. Three cases are presented with description
      of a mechanism common to both injuries that may explain this association--that of
      distraction and hyperflexion, such as occurs in seat-belt injuries. Whenever a
      transverse lumbar spine fracture following such a mechanism of injury is
      recognized, the co-existence of an injury to the abdominal aorta should be
      excluded by aortography if there is any doubt concerning the integrity of the
      peripheral pulses. This is best performed prior to laparotomy for any associated
      intraperitoneal injuries. Repeated clinical examination may detect deterioration
      in those cases with initially normal pulses. Ultimately, detection of the aortic
      injury rests on a high index of suspicion.

PMID- 8536394
TI  - Accuracy of CT in predicting the cause of bronchiectasis.
AB  - There are many reports that state that the distribution and pattern of
      bronchiectasis may be sufficiently characteristic for a specific cause to be
      suggested. The aim of this study was to determine whether experienced chest
      radiologists could confidently and accurately diagnose various aetiologies of
      bronchiectasis from the computed tomography (CT) pattern of disease alone. CT
      scans of 108 patients with bronchiectasis of various causes (67 with idiopathic
      bronchiectasis, 10 with allergic bronchopulmonary aspergillosis, 12 with
      syndromes of impaired mucociliary clearance, 12 with hypogammaglobulinaemia and
      seven with adult cystic fibrosis) were assessed by three chest radiologists
      without knowledge of clinical data. Each observer listed the three most likely
      diagnoses in order of probability. In addition, a level of confidence on a 3
      point scale was assigned to the first choice diagnosis. A correct first-choice
      diagnosis was made in 45% of readings. A high confidence level was given in only
      9% of the first choice readings. Of these, a correct diagnosis was reached in
      35%. There was poor interobserver agreement (mean kappa = 0.20). In conclusion,
      we found that the causes of bronchiectasis cannot be reliably diagnosed on the
      basis of CT appearances alone.

PMID- 8536395
TI  - Childhood lymphoma: diagnostic accuracy of chest radiography for severe pulmonary
      complications.
AB  - INTRODUCTION: We sought to determine whether chest radiography can be reliably
      used to distinguish persistent or relapsing pulmonary lymphoma from a variety of
      infectious and noninfectious pulmonary conditions that can occur in children
      receiving treatment for lymphoma. METHODS: We studied chest radiographs of 37
      patients (30 with non-Hodgkin's lymphoma, and seven with Hodgkin's disease) who
      died of paediatric lymphoma or of treatment complications. Pulmonary findings at
      autopsy comprised lung tumour (n = 14), pleural tumour (n = 12), pneumonia (n =
      22), adult respiratory distress syndrome (ARDS; n = 16), haemorrhage (n = 27),
      and infarction (n = 13). Using a 4-point scale and without knowledge of autopsy
      findings, three radiologists independently rated antemortem radiographs for the
      presence of pulmonary tumour, pleural tumour, pneumonia in general, pneumonia
      caused by viral, bacterial, fungal, and protozoan pathogens, ARDS, pulmonary
      haemorrhage, and pulmonary infarction. Diagnostic accuracy was defined by the
      area under the receiver-operating-characteristic curve (AZ). RESULTS: Diagnostic
      accuracy was good for pulmonary tumour (AZ, 0.71 +/- 0.6), protozoan pneumonia
      (AZ, 0.77 +/- 0.06), and ARDS (AZ, 0.86 +/- 0.07) but poor for all other
      conditions. The absence of both pleural effusions and mediastinal/right hilar
      lymphadenopathy was significantly associated (P < or = 0.04) with the absence of
      lung tumour. DISCUSSION: The pulmonary processes in these patients can all
      demonstrate diffuse airspace opacification, and many patients had multiple lung
      abnormalities at autopsy. The radiologist-readers were unable to identify which
      pulmonary conditions were responsible for radiographic findings in most patients.
      The readers were able to identify patients who did not have pulmonary lymphoma.
      If pulmonary involvement with lymphoma is unlikely, bronchoscopy with
      bronchoalveolar lavage may be sufficient to establish a diagnosis. When pulmonary
      lymphoma is a clinical consideration, open lung biopsy is usually required for
      diagnosis.

PMID- 8536396
TI  - Digital subtraction in Gd-DTPA enhanced imaging of the breast.
AB  - PURPOSE: This study examines the role of digital subtraction magnetic resonance
      imaging (MRI) of the breast in the interpretation of the morphology and
      characteristics of breast disease. METHODS: Thirty-one patients with an abnormal
      mammogram or clinically palpable abnormality underwent MRI of the breast prior to
      surgical excision of the lesion. FLASH 3-D images of the breast were acquired
      before and after IV contrast injection of Gd-DTPA. Digital subtraction was
      performed on selected images. The images were independently assessed by two
      radiologists experienced in both mammography and MRI. RESULTS: Accurate diagnosis
      was possible in 29 out of 31 patients using the subtraction technique compared to
      23 cases using the pre-subtraction images alone. The actual extent of disease and
      multicentricity were also better appreciated on the subtracted image. Subtraction
      also provided better identification of tumour recurrence in the post-operative
      and post-radiotherapy breast. Chest wall and lymph node involvement were more
      easily appreciated on the subtraction images. CONCLUSION: Digital subtraction is
      a simple, effective and relatively cheap technique which can aid in the
      interpretation of magnetic resonance imaging of the breast.

PMID- 8536397
TI  - The antenatal diagnosis and management of abdominal wall defects: the northern
      region experience.
AB  - One hundred and twenty abdominal wall defects were notified to the Northern
      Region Fetal Abnormality Survey in the five years 1988 to 1992. Gastroschisis
      occurred in 56, exomphalos in 43, amnion rupture in 11, ectopia vesicae in seven
      and ectopia cordis in three. Ultrasound failed to identify gastroschisis in 14
      and incorrectly diagnosed exomphalos in eight. There was no associated chromosome
      abnormality and the survival rate, excluding first trimester loss, was 87%.
      Ultrasound failed to identify exomphalos in ten and incorrectly diagnosed
      gastroschisis in two. Another structural abnormality was present in 40% and a
      chromosome anomaly in 28%. Excluding spontaneous first trimester loss, the
      survival rate was 34%. Delivery of babies away from the regional paediatric
      surgical centre did not adversely affect the outcome in gastroschisis or
      exomphalos although closure was delayed, on average, by 2 h. There was one
      survivor of 11 fetuses with amnion rupture sequence. Six of the seven babies with
      ectopia vesicae and two of the three with ectopia cordis survived.

PMID- 8536398
TI  - Fluoroscopically-guided retrieval of ureteric stents.
AB  - Percutaneous fluoroscopically-guided retrieval of seven dysfunctional ureteric
      stents was performed in five patients (four male, one female) over an 18 month
      period. The technical aspects of the procedure are discussed and the preferred
      method using rigid forceps is described.

PMID- 8536399
TI  - Diagnosis of acute ureteral calculous obstruction in pregnant women using colour
      and pulsed Doppler sonography.

PMID- 8536400
TI  - Technical report: percutaneous transperitoneal balloon sphincteroplasty during
      laparoscopic cholecystectomy for choledocholithiasis.

PMID- 8536401
TI  - Case report: an unusual mass in the breast: the hydatid cyst.

PMID- 8536403
TI  - Case report: treatment of a carotid artery pseudoaneurism with a polyester
      covered nitinol stent.

PMID- 8536402
TI  - Case report: apical pleural cap mimicked by post-traumatic pseudomeningocele.

PMID- 8536404
TI  - Case report: multiple myeloma--a cause of obstructive jaundice.

PMID- 8536405
TI  - Case report: iliac artery rupture--percutaneous treatment by stent insertion.

PMID- 8536407
TI  - The display and perception of 3-D information applied to X-ray images.

PMID- 8536406
TI  - A comparison of clinical and MR staging of bladder carcinoma.

PMID- 8536408
TI  - Diagnosis of fetal vesico ureteric reflux as the cause of pelvicalyceal
      dilatation on antenatal ultrasound.

PMID- 8536409
TI  - HIP survey of breast cancer screening.

PMID- 8536410
TI  - Delayed CT findings in acute renal infection.

PMID- 8536411
TI  - Contrast medium reactions.

PMID- 8536412
TI  - Demonstration of popliteal artery entrapment on leg muscle scintigraphy.

PMID- 8536413
TI  - Absolute versus proportional differential leucocyte counts.
AB  - Comparison of absolute (cells x 10(9)/l) leucocyte differential counts with
      proportional (percentage) counts from the same stained films demonstrates
      significant disparities between these two methods of reporting results. Within
      reference intervals the disparities are modest but become significant in
      specimens with distributional abnormalities. Although neither method of reporting
      is formally espoused in this communication, it is suggested that use of the
      absolute count is more likely to provide diagnostic support.

PMID- 8536414
TI  - An assessment of the Coulter VCS automated differential counter scatterplots in
      the recognition of specific acute leukaemia variants.
AB  - The Coulter VCS is an automated differential counter, which derives a five-part
      differential count on the basis of differences in cell volume, high frequency
      conductivity and light scatter. A printed scatterplot relating volume and scatter
      is readily obtained. Other instruments which use automated cytochemistry can
      distinguish between AML and ALL, and between AML variants. It was our impression
      that the Coulter VCS might also be capable of such distinction on the basis of
      the scatterplot patterns. We therefore collected scatterplots produced by Coulter
      VCS analysis of peripheral blood from 63 patients presenting with acute
      leukaemia. The scatterplots were inspected and six basic patterns identified. The
      scatterplots were inspected and six basic patterns identified. The scatterplots
      could be reproducibly sorted into pattern-specific groups without knowledge of
      the diagnosis. Precise leukaemic diagnoses were made routinely by conventional
      morphology, cytochemistry and immunophenotyping. A comparison was then made with
      the scatterplot patterns. The 51 cases of AML produced examples of all six
      patterns. The nine cases of ALL produced only three patterns. These were shared
      with cases of AML, and two were also shared with the three cases of acute mixed
      lineage leukaemia. Thus, three of the six patterns were specific for AML, whereas
      no pattern was specific for ALL or acute mixed lineage acute leukaemia. One
      pattern was produced only by the three cases of AML M6, and another was produced
      only by five of the 25 cases of primitive (M0 and M1) AML.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8536415
TI  - The effects of cigarette smoking and alcohol consumption on blood haemoglobin,
      erythrocytes and leucocytes: a dose related study on male subjects.
AB  - The objective of this study was to quantify the combined dose related effects of
      cigarette smoking and alcohol consumption on blood haemoglobin concentration,
      erythrocytes and leucocytes. The subjects consisted of 17,670 males attending for
      routine health screening, with an average age of 43 years and a range of 16-91
      years. The number of cigarettes smoked each day was divided into six categories,
      and declared alcohol consumption into seven. Of the 42 different combinations of
      smoking and drinking groups, five were not reported because they contained less
      than 30 subjects. Haemoglobin concentration was significantly increased in those
      smoking more than 10 cigarettes per day. Smoking also increased the PCV. Alcohol
      had no effect on Hb or PCV. The red cell count was reduced by alcohol
      consumption, with even the lowest consumption producing a significant decrease.
      Both smoking and drinking raised the MCV in a linear dose relationship. The
      marked increase in white cell count with smoking was seen even in subjects
      smoking 10 cigarettes per day or less. It is suggested that social habits such as
      smoking and drinking should be considered when interpreting blood haematology
      values. Changes in haematology results could be used to encourage a healthier
      lifestyle.

PMID- 8536416
TI  - Serum erythropoietin during autologous bone marrow transplantation: relationship
      to measures of erythroid activity.
AB  - Marked elevation of serum erythropoietin (sEPO) occurs following high dose
      chemotherapy for malignant disease. It has been proposed that the subsequent fall
      in sEPO constitutes a relative erythropoietin (EPO) deficiency, prompting trials
      of recombinant EPO to reduce red cell transfusion during chemotherapy. We have
      investigated these phenomena by serial estimations of reticulocytes and sEPO in
      11 autologous marrow transplant recipients. sEPO reached two to five times
      baseline 0 to 5 days after transplant but the inverse relationship between sEPO
      and haematocrit was maintained. Observed to expected log sEPO (Epo ratio) rose
      and fell in parallel with sEPO, remaining greater than 1.0 throughout. A
      progressive fall in reticulocyte count during chemotherapy was followed by an
      increase during engraftment. The strong inverse relationships between
      reticulocytes and Epo ratio in the 10 days after initiating chemotherapy support
      the hypothesis that loss of EPO-receptor bearing erythroid precursors allows a
      rise in sEPO during chemotherapy. The elevation of Epo ratio levels during
      engraftment indicates that it is the availability of EPO-sensitive progenitors,
      rather than the supply of EPO, that limits the rate of resumption of
      erythropoiesis after high-dose chemotherapy.

PMID- 8536417
TI  - Evaluation of a semi-automated reticulocyte counting method using the Coulter
      STKS-2A blood cell counter.
AB  - Reticulocyte counting was assessed on the Coulter STKS-2A automated blood cell
      counter. Using a two step procedure, blood samples were first incubated with the
      supravital stain new methylene blue. An acidic reagent was then added to clear
      the haemoglobin and any stained RNA was preserved within the cell. The cells were
      then analysed by measurement of volume, conductivity and light scatter (VCS). The
      results of 123 samples analysed on the STKS-2A were compared with those from a
      Toa Sysmex R-1000 reticulocyte counter. One hundred and seven samples gave no
      review flags and reticulocyte counts ranging from 0.5% to 22.8%, resulting in a
      correlation coefficient of 0.93 for the methods. Between run imprecision studies
      gave CVs ranging from 5.3% for a reticulocyte count of 8.7% to a CV of 16.3% for
      a 0.34% count. Stability studies showed insignificant changes over 72 h storage.
      These findings confirm that VCS technology can be adapted to provide precise and
      accurate routine reticulocyte analysis.

PMID- 8536418
TI  - New indices from the H*2 analyser improve differentiation between heterozygous
      beta or delta beta thalassaemia and iron-deficiency anaemia.
AB  - The two main causes of microcytic and hypochromic anaemia are iron deficiency
      (IDA) and thalassaemia (THAL) traits. In the Mediterranean area there is a high
      prevalence of beta and delta-beta THAL minor. The differentiation between these
      causes of microcytosis can be significantly improved with two new indices,
      percentage of microcytes (%Mi) and percentage of hypochromic red blood cells
      (%Hy), and the direct determination of MCHC, provided by the technological
      advances of the H*2 analyser. Our discriminant analysis, based on the
      minimization of Wilk's lambda (lambda) criterion, was used to select the best
      predictive variables to differentiate between IDA and THAL and has resulted in
      the highest diagnostic efficiency published to date. The discriminant function
      obtained is a simple linear combination of the following variables: D = 1.145 RBC
      0.174 MCV + 0.091 MCHC + 0.787 square root of (%Hy/%Mi)-22.119. The overall
      correct classification was 97.6% on the training sample (79 THAL and 90 IDA) and
      96.7% on a validation sample of microcytic patients (72 THAL and 80 IDA). The
      sensitivity and diagnostic specificity were 97.5% and 97.8%, respectively, for
      the training sample, and 95.8% and 97.5% for the control group.

PMID- 8536419
TI  - Optimal haematocrit and haemoglobin S levels in pregnant women with sickle cell
      disease.
AB  - Sickle cell blood has abnormal rheological characteristics and its viscosity is
      determined by the level of haemoglobin S and the PCV. Rheological studies have
      shown that alteration of these parameters will improve oxygen delivery to the
      tissues. However, there is no agreed policy for optimum levels for haemoglobin S
      and PCV in the management of pregnancies complicated by sickle cell disease. In
      this study rheological measurements have been performed on pregnant women with
      sickle cell disease and compared with women without haemoglobinopathy. Potential
      oxygen delivery was not found to approach normal levels until very low levels of
      HbS were achieved. The optimal PCV for women with sickle cell disease was found
      to be 0.26 compared with 0.33 for normal women.

PMID- 8536420
TI  - Enumeration of platelets by multiparameter flow cytometry using platelet-specific
      antibodies and fluorescent reference particles.
AB  - The correct enumeration of platelets is still an elusive matter. This is mainly
      due to the fact that commercial instruments which are used for platelet counting
      cannot discriminate platelets from other cellular particles and precipitates that
      cause similar signals. Visual (chamber counting) methods are still frequently
      used in routine laboratories to verify low automated platelet counts (< 50 x
      10/l) despite obvious technical and statistical drawbacks. The following report
      shows how platelet counts can be measured by multiparameter flow cytometry with
      the help of reference particles (fluorescent latex beads) and platelet-specific
      antibodies i.e. anti-GPIIb/IIIa(CD41a), anti-GP Ib-alpha (CD42b) and anti-GP IIIa
      (CD61). The linearity of this method was highly satisfactory and the observed
      imprecision was within acceptable limits. At a platelet concentration of 10 x
      10(9)/l the coefficient of variation (CV, n = 10) ranged from 5.3% (PCV = 0.456)
      to 5.6% (PCV = 0.148). Accuracy was evaluated by comparing results to the ICSH
      selected method for platelet counting. The correlation of both methods was
      significant (P < 0.005) and Passing-Bablok's linear regression analysis showed no
      systematic differences between the two methods. Comparisons of this new platelet
      counting technique were also performed with routine visual methods, automated
      blood analysers (Technicon H-1, Sysmex E-5000) and a different flow cytometric
      method using only forward and side light scatter properties of platelets for
      their discrimination. The linear correlation of all methods was significant (P <
      0.01) at platelet concentrations above 50 x 10(9)/l. At lower platelet
      concentrations, our new platelet counting technique correlated significantly only
      with the visual and the forward/side scatter methods.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8536421
TI  - The effects of time from venepuncture and choice of anticoagulant on mean
      platelet volume estimations.
AB  - The Mean Platelet Volume (MPV) is a readily measured parameter using modern
      automated cell counters. Despite studies which indicate that MPV may be altered
      in various disease states, its widespread application has been hindered by its
      known dependence on factors such as time from venepuncture, choice of
      anticoagulant and sample storage temperature. In this report we describe the
      changes in MPV measured on a Technicon H1 analyser with time from sampling using
      two different anticoagulants under clinical laboratory conditions. Small changes
      in MPV with time were seen in both anticoagulants. These were statistically
      significant by Student's paired t-test but, on analysis of variance, were not
      significant compared with the variation in MPV between individuals. The well
      documented effects of time, temperature and anticoagulant on MPV need not
      interfere with the interpretation of a result from a sample dealt with under
      similar conditions to those applying in this study.

PMID- 8536423
TI  - Haemolytic transfusion reactions due to Mi-antibodies; need to include
      MiltenbergerIII positive cells in pre-transfusion antibody screening in Hong
      Kong.

PMID- 8536422
TI  - The sustained impact of a group and screen and maximum surgical blood ordering
      schedule policy on the transfusion practice in gynaecology and obstetrics.
AB  - A retrospective study was carried out to examine the durability of the impact of
      Group and Screen (GS) and Maximum Surgical Blood Ordering Schedule (MSBOS) policy
      on transfusion practices. The study involved the Gynaecology and Obstetrics wards
      of the three Aberdeen teaching hospitals, all of which are supplied with blood
      and services by the transfusion laboratory of Aberdeen and North East of Scotland
      Blood Transfusion Service. The transfusion laboratory and hospital records were
      examined and analysed for all transfusion events in Gynaecology and Obstetrics
      during the three periods of 6 months immediately before, immediately after and 2
      1/2-3 years following the introduction of a GS and MSBOS policy in November 1986.
      The number of units of blood crossmatched and units transfused decreased
      consistently and progressively to half the pre-GS and MSBOS level in both
      Gynaecology wards and Obstetrics wards during the study periods. This reduction
      was not associated with a decrease in the clinical workload. However, the
      crossmatched/transfused ratio (CTR) showed an immediate but transient improvement
      (3.6 to 2.2 to 3.4) and only partial and delayed improvement (10.1 to 9.6 to 7.7)
      with regard to blood use in the Gynaecology wards and the Obstetrics wards
      (respectively) during the three periods of 6 months indicated above. We conclude
      that the introduction of a GS and MSBOS policy can have a significant and
      sustained impact in reducing unnecessary blood ordering. The CTR may not be as
      sensitive an indicator of the effect of the introduction of GS and MSBOS as the
      total blood usage and a more detailed examination of blood use is necessary to
      assess performance and long-term impact.

PMID- 8536424
TI  - Evaluation of factors influencing precision in the analysis of samples taken from
      blood spots on filter paper.
AB  - Dried blood spots (DBS) on filter paper have potential as a collection method in
      screening for haematinic deficiencies. Factors influencing the volumetric
      precision of uniform 'centre' punches (6.35 mm diameter) removed from dried blood
      spots have been evaluated. The volume of blood in each DBS punch (n = 234) was
      greatly influenced by both sample haematocrit (r = 0.63) and haemoglobin
      concentration (r = 0.63). The volume in identical punches (n = 57) also differed
      significantly when measured independently using either 125I human serum albumin
      or haemoglobin relative to the original blood sample. DBS punch volumes should be
      predetermined for individual batches of filter paper using the specific analyte
      of interest.

PMID- 8536425
TI  - Re-evaluation of Evans blue dye dilution method of plasma volume measurement.
AB  - To simplify the method of plasma volume measurement by Evans blue dye dilution we
      used, for the first time, the same venous site for injection of dye and
      collection of samples. In a series of 49 studies the dye decay between 10 and 35
      min after injection was highly linear (r = 0.991 +/- 0.01), indicating that
      contamination of samples is very unlikely. We repeated the measurements after
      eight weeks in nine patients; the mean difference was 16.4 +/- 19.6 ml,
      indicating a high degree of reproducibility. We found that extrapolation of the
      dye decay curve to time zero is required for accurate estimates of plasma volume.
      There was good agreement between the estimates of plasma volume obtained by
      extrapolation from only three samples taken at 10, 20 and 30 min after dye
      injection with the results obtained using all six samples. We also found good
      agreement between the estimates of plasma volume obtained by using standard
      curves constructed from four standard dilutions of 1.25, 2.5, 5 and 10 mg/l and
      those obtained by the use of standard curves constructed from the blank and only
      one standard dilution of 10 mg/l. We therefore conclude that the Evans blue
      technique can be simplified with minimal loss of accuracy, by using only one
      venous site for injection and withdrawal, withdrawing only three samples between
      10 and 30 min after injection and using a two point calibration line.

PMID- 8536426
TI  - Retroperitoneal haematoma in a patient treated with acenocoumarol, phenytoin and
      paroxetine.
AB  - Coumarin anticoagulants must be strictly monitored because of their narrow
      therapeutic index and their potential interactions with other drugs. The high
      probability of interactions can be explained by two pharmacokinetic properties of
      coumarins: high binding to plasma albumin (99%), being displaced by other drugs
      with greater affinity to this protein, and metabolism by liver microsomal enzymes
      (cytochrome P450), which can be induced or inhibited by other compounds (Shinn &
      Shrewsbury 1985). A case is reported of a clinically relevant drug interaction of
      phenytoin and acenocoumarol, possibly potentiated by concomitant treatment with
      paroxetine, leading to a retroperitoneal haematoma.

PMID- 8536427
TI  - Use of interferon-2 alpha in the treatment of cryoglobulinaemic leg ulcers.
AB  - We report three cases of leg ulcers complicating cryoglobulinaemia which resisted
      conventional therapy but responded to interferon-2 alpha. All three cases
      improved with the complete resolution of painful vasculitic lesions and healing
      of deep ulcers. The dose of interferon to produce ulcer healing was determined by
      individual response with escalation of the daily dose to 4.5 x 10(6) units per
      day required in one case. A lower dose of maintenance interferon could be used to
      prevent subsequent relapses of disease.

PMID- 8536428
TI  - Clinical goals for the precision of complete blood counts.

PMID- 8536429
TI  - High serum folate and the calculation of red cell folate.

PMID- 8536430
TI  - Paraneoplastic cerebellar degeneration: a rare presentation of Hodgkin's disease.

PMID- 8536431
TI  - [Physiopathology of lipid metabolism and liver changes in obesity].

PMID- 8536432
TI  - [Interferons in the therapy of solid tumors].
AB  - Belonging to the vast family of cytokines, interferons (IFN) have recently been
      widely investigated concerning their possible clinical applications, both in
      virology and oncology. In this field results have been quite mixed but definitely
      encouraging. The best achievements have been obtained in hematology, and
      particularly in the treatment of hairy cell leukemia and chronic myelogenous
      leukemia, but new perspectives have also opened in the therapy of solid tumors,
      especially in the local treatment of superficial bladder cancer and ovarian
      cancer, AIDS-related Kaposi's sarcoma and malignant melanoma. IFN have in certain
      cases showed an efficacy comparable to that of classic treatments but with lower
      toxicity, and in some tumors they have even improved the results obtained so far,
      especially in combined therapy. We have here gathered the most recent results
      concerning the use of IFN in the therapy of solid tumors in order to highlight
      the new therapeutic opportunities available to clinical oncology.

PMID- 8536433
TI  - Hyperlipidemia, hypertension and atherosclerosis in women. Reality and
      perspectives.
AB  - The prevalence of ischemic cardiopathy is different from country to country, race
      to race, although there is a constant greater prevalence among males. After a
      certain age there is a modification of the ratio between males and females; but
      this ratio, before and after menopause, is varying in time and to a certain
      extent is due to the intervention of new risk factors or the greater influence of
      the traditional factors which are not age related. in this review are analyzed,
      with greater emphasis on the female sex, the major risk factors for the ischemic
      cardiopathy, their dependence on hormonal status before and after menopause, and
      the different life styles and behaviours that are probably influenced by
      ethnologic factors, in the so called advanced societies.

PMID- 8536434
TI  - [Role of CT in the evaluation of patients with painful symptoms located in the
      lower right abdominal quadrant].
AB  - Eleven patients presenting signs and symptoms related to flogistic disease of the
      right inferior abdominal region were studied with Computed Tomography. Four out
      of the eleven patients also underwent Magnetic Resonance examination. In 9
      patients final diagnosis was correctly reached after surgery and in 1 case
      diagnosis was made on the basis of endoscopic findings and delayed echographic
      controls. Among the eleven patient a correct diagnosis was possible on the basis
      of CT findings in seven of the examined patients; 4 of them were correctly
      diagnosed as appendicitis; 1 case was diagnosed as Crohn disease; 1 case was a
      mucocele and 1 case was diagnosed as tubo-ovaric abscess. In 1 case no one
      diagnostic hypothesis was possible on the basis of CT and MR findings; on surgery
      the diagnosis was of appendicitis. In 2 cases of surgery proven tubo-ovaric
      abscesses a diagnosis of appendicitis was done on the basis of CT examination. In
      one case CT and MR findings were considered to be related to an ovaric tumor; on
      surgery the correct diagnosis was of post-surgical fibrosis. In 4 cases MR
      findings confirmed the diagnostic hypothesis reached with CT examination but only
      in two of them the final diagnosis was correct. In this paper we describe all the
      CT and MR findings found in each patient.

PMID- 8536435
TI  - [Intestinal carcinoids. Clinical consideration on four cases].
AB  - Four cases of intestinal carcinoids are described. Authors remake considerations
      about diagnosis and treatment in this field.

PMID- 8536436
TI  - [A case of non-Hodgkin T-cell lymphoma with predominantly cutaneous
      manifestations].
AB  - There is a wealth of experiences concerning cancer and leukemia induced in human
      populations by radiation. The contribution of the nuclear industry to the
      radiation exposure of the general population is small, but there is the risk of
      catastrophic accidents causing a large number of deaths. The authors describe the
      case of a 48 year old black man accidentally exposed to the effects of radiations
      during the nuclear disaster of Chernobyl in 1986. The patient showed, many years
      later, a predominantly cutaneous high-grade T cell lymphoma, which was refractory
      to traditional treatments but sensitive to high doses of a recombinant
      interferon. Unluckily the patient died, six months later, because of
      autoinfection overwhelming. The goal of the authors is again to ask to reflect on
      the risk of the use of nuclear power and to debate the possible choice of the
      still experimental treatments.

PMID- 8536437
TI  - [Microcirculation: possibility of non-invasive diagnosis].

PMID- 8536438
TI  - Sleep disorders.

PMID- 8536439
TI  - Current concepts of fatal asthma.

PMID- 8536440
TI  - Etiopathogenesis and management of pneumonia.

PMID- 8536441
TI  - Bronchodilator therapy in the management of acute asthma.
AB  - Bronchodilator management of acute severe asthma has evolved considerably in
      recent years. beta-adrenergic agonists have emerged as the single most potent
      class of bronchodilator available, and the inhalational route of administration
      has proven to be the most effective and least toxic method of delivery except
      among apneic or highly uncooperative patients. Other bronchodilators, including
      aminophylline, inhaled anticholinergics, and intravenous magnesium sulfate, are
      significantly less potent drugs for reversal of bronchoconstriction. In most
      patients these agents do not promote significant bronchodilation beyond that
      achieved with an intensive regimen of inhaled beta agonists; subsets of patients
      that might benefit from these other agents remain to be identified. Questions
      remain as to the optimal dose, frequency of administration, and mode of
      inhalational delivery of the beta agonists in acute asthma. Finally, it is
      important to remember that bronchodilator therapy constitutes only one component
      in the treatment of acute severe asthma. Treatment of airway inflammation with
      systemic corticosteroids is another vital component, as are supplemental oxygen
      in the hypoxemic patient, close monitoring of lung function, attention to the
      possibility of hypercapnic respiratory failure, patient education, and a plan of
      care following emergency department discharge.

PMID- 8536442
TI  - Spirometry for the primary care physician.
AB  - The clinician wishing to employ a spirometer in the office must be aware of the
      equipment available and the current standards for validating and maintaining such
      equipment. Indications for spirometry are fairly frequent in general medical
      practice for both diagnosis, response to therapy, and for risk assessment prior
      to surgery. The criteria for characterizing a spirogram as normal, obstructive or
      restrictive, are well defined. The information obtained may be very helpful to
      point to additional specific diagnostic studies or to outline a specific
      treatment plan.

PMID- 8536443
TI  - Lung cancer screening.

PMID- 8536444
TI  - The acute respiratory distress syndrome: current trends in pathogenesis and
      management.
AB  - Management of patients in ARD remains a complex diagnostic and difficult
      therapeutic problem. Although the authors have focused on several new and
      exciting management strategies, it is important to recognize that the vast
      majority of patients with ARDS simply require meticulous general medical care. In
      this era of invasive monitoring and other care. In this era of invasive
      monitoring and other complex technologies, there is sometimes a tendency to
      neglect the basic issues such as judicious use of antibiotics to avoid
      superinfection with resistant organisms or antibiotic-associated diarrhea;
      removal of unnecessary intravenous lines to minimize line related infections; and
      maintenance of adequate nutrition to promote good skin and mucosal integrity as
      well as preserving important muscle mass all too often receive a low priority. It
      is anticipated that with meticulous general medical care, as well as selective
      implementation of the above treatment strategies, improvement in the outcome of
      patients is an achievable goal.

PMID- 8536445
TI  - Update in the treatment and molecular biology of non-small cell lung cancer.

PMID- 8536446
TI  - The effect of monophasic combinations of ethinyl estradiol and norethindrone on
      gonadotropins, androgens and sex hormone binding globulin: a randomized trial.
AB  - The effects of different monophasic combinations of ethinyl estradiol and
      norethindrone on FSH, LH, sex hormone binding globulin, total testosterone,
      androstenedione, and dehydroepiandrosterone sulfate levels in non-obese, non
      hirsute women were compared. Retrospective analysis of frozen serum from a
      prospective randomized trial in which women received one of three oral
      contraceptive pills containing ethinyl estradiol 50 micrograms/norethindrone 1
      mg, ethinyl estradiol 35 micrograms/norethindrone 1 mg or ethinyl estradiol 35
      g/norethindrone 0.5 mg for nine cycles was conducted. Blood samples were obtained
      prior to treatment and during the third, sixth and ninth pill cycles. Ethinyl
      estradiol 50 micrograms/norethindrone 1 mg and ethinyl estradiol 35
      micrograms/norethindrone 1 mg suppressed FSH, LH, and total testosterone and
      increased sex hormone binding globulin to a similar degree. Ethinyl estradiol 35
      micrograms/norethindrone 0.5 mg resulted in less suppression of FSH, LH, and
      total testosterone, but greater elevation of sex hormone binding globulin.
      Dehydroepiandrosterone sulfate was suppressed to a similar degree with ethinyl
      estradiol 35 micrograms/norethindrone 1 mg and ethinyl estradiol 35
      micrograms/norethindrone 0.5 mg, but ethinyl estradiol 50
      micrograms/norethindrone 1 mg resulted in the least suppression of
      dehydroepiandrosterone sulfate. Ethinyl estradiol 35 micrograms/norethindrone 1
      mg caused greater suppression of androstenedione than did the other two oral
      contraceptives. Oral contraceptive-induced changes in gonadotropins, androgens,
      and sex hormone binding globulin can be predicted by considering the relative
      amounts of estrogen and progestin in the pill. When combined with 1 mg of
      norethindrone, 50 micrograms of ethinyl estradiol did not result in greater
      suppression of FSH, LH, or total testosterone or in greater elevation of sex
      hormone binding globulin than did 35 micrograms of ethinyl estradiol.

PMID- 8536447
TI  - The effects of nomegestrol acetate subdermal implant (Uniplant) on carbohydrate
      metabolism, serum lipoproteins and on hepatic function in women.
AB  - This study was undertaken to assess possible variations in body weight, blood
      pressure, fasting glucose, HbA1C, insulin, total cholesterol, HDL-C, LDL-C,
      triglycerides, SGPT, SGOT, GGT and bilirubin in women bearing a single subdermal
      Silastic implant containing 55 mg (10%) of nomegestrol acetate during two years.
      A total of eighteen volunteers of reproductive age who desired to avoid
      conception were enrolled in this study. Subjects were healthy women with no
      contraindications to hormonal contraception. All women were investigated before
      starting treatment and were followed up for one year. At the end of one year the
      capsules were removed and a new capsule was inserted. Fasting blood samples were
      drawn at 8:00 to 8:30 am twice prior to implant insertion and then at the first,
      third, sixth and twelfth months and every six months thereafter. Body weight
      increased from 54.9 +/- 1.5 kg at admission to 55.3 +/- 2.0 kg at 12 months of
      use (p < 0.05) and to 56.0 +/- 2.7 kg at 24 months of use. A slight increase in
      both systolic and diastolic blood pressure was recorded at month 12 (p < 0.01).
      At month 24, blood pressure was not significantly different from admission
      values. All levels were within the normal range. Insulin, HbA1C, LDL-C and GGT
      remained unchanged during twenty-four months of Uniplant use. A significant
      decrease in total cholesterol (p < 0.05) was observed in the third month while a
      significant decrease in HDL-C (p < 0.01) was observed only in the sixth month of
      Uniplant use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536448
TI  - Effect of testosterone enanthate on serum lipoproteins in man.
AB  - Sixty-three normal Caucasian men were administered intramuscular testosterone
      enanthate (TE) 200 mg i.m. weekly for 12 months as part of a male contraceptive
      trial. This dose of TE caused a 2.5-fold increase in trough serum testosterone
      concentrations. High density lipoprotein cholesterol (HDL-C) was significantly
      depressed from pretreatment concentration of 1.19 +/- 0.04 nmol/l to 1.03 +/-
      0.04 mmol/l after 12 weeks of treatment, and remained suppressed for the duration
      of treatment (p < 0.001). There were no changes in serum concentration of total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C) or triglycerides
      (TG) during treatment, but the concentrations of TC and LDL-C were depressed at
      three months post-treatment. There was a sustained elevation in LDL-C:HDL-C ratio
      during TE treatment (p < 0.005), from 3.41 +/- 0.15 pretreatment to 3.88 +/- 0.19
      after 12 weeks of TE treatment. Sex hormone binding globulin (SHBG), but not
      testosterone (T) or estradiol (E2), was significantly associated with HDL-C (r =
      0.83, p = 0.001). Lipoprotein (a) (Lp(a)) was measured in a subgroup of 33 men:
      serum concentration fell from 187 +/- 45 mg/l pretreatment to 140 +/- 35 mg/l
      after 16 weeks of TE treatment (p < 0.01).

PMID- 8536449
TI  - Effects of testosterone buciclate on testicular and epididymal sperm functions in
      bonnet monkeys (Macaca radiata)
AB  - The effects of testosterone buciclate (TB), a long-acting androgen ester given
      i.m. at four sites (20 mg/site) on days 1 and 91 of the study period (360 days),
      on reproductive and hormonal parameters were evaluated in five adult male bonnet
      monkeys; untreated animals (n = 5) acted as controls to monitor seasonal changes
      in these parameters. In control animals, testicular volume remained unchanged
      throughout the study; sperm count, motility and gel penetrability decreased while
      the percentage of spermatozoa showing retention of cytoplasmic droplet and coiled
      tail increased in June-July (days 210-240), preceded by reduction in serum
      testosterone (T) levels on days 120-150 (March-April). The TB-treated animals
      showed reduced testicular volume (days 90-270), suppressed sperm motility and gel
      penetrability (days 45-240 except on day 120), decreased sperm count (days 75
      270), and an increased percentage of spermatozoa showing retention of cytoplasmic
      droplet and coiled tail (days 45-240 except on day 120). Even though serum T
      levels remained elevated until day 300, these levels were within the
      physiological range. The changes induced by TB were reversible. The suppression
      of testicular and epididymal functions by TB indicates that this long-acting
      androgen may have the potentiality to induce and maintain reversible sterility,
      but further evaluation needs to be carried out to develop an appropriate dosage
      regimen that would prevent return to normal functions in order to develop this
      long-acting androgen as a hormonal male contraceptive.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8536451
TI  - The TCu 380A IUD and the frameless IUD "the FlexiGard": interim three-year data
      from an international multicenter trial. UNDP, UNFPA, and WHO Special Programme
      of Research, Development and Research Training in Human Reproduction, World Bank:
      IUD Research Group.
AB  - The TCu 380A and FlexiGard IUDs were compared in a randomized multicenter trial
      including 28 institutes in 13 countries. There were 53 insertion failures with
      the FlexiGard and one with the TCu 380A. There were 2184 successful insertions of
      the TCu380A and 2102 of the FlexiGard device. The three-year pregnancy rates for
      the TCu 380A and FlexiGard were similar (1.6 and 1.9 per 100 women, respectively)
      but the FlexiGard three-year expulsion rate (7.4 per 100 women) was significantly
      higher than that of the TCu 380A (4.4 per 100 women). The insertion technique for
      the FlexiGard needs to be improved in order to lower the expulsion rate.

PMID- 8536450
TI  - Biological activity in the repopulating rat spermatocyte after the withdrawal of
      gossypol treatment. VI. Alteration in nuclear factors for interaction with
      histone gene promoter.
AB  - This article reports the effects of gossypol at the genomic level in rat
      spermatogenic cells. After gossypol treatment for various times (8, 12, and 19
      weeks), the spermatogonial cells were allowed to rest for 2 to 4 weeks. The
      function of histone H4 gene promoter (H4GP) in the repopulating pachytene
      spermatocytes (RPS) was investigated. The sequences of the oligonucleotides for
      the H4GP binding sites 1 and 2 were synthesized by an ABI-392 DNA synthesizer.
      RPS and the control pachytene spermatocytes (CPS) were obtained by centrifugal
      elutriation and subsequently they were used for the preparation of nuclear
      protein extracts (NPE). The NPE interaction with the DNA fragment of site 1 or 2
      was studied by an electrophoresis mobility shift assay (EMSA). EMSA with NPE-CPS
      revealed ten major gel shift bands for site 1 and 2. The presence of extra
      unlabelled DNA fragments competed with 6 of the bands. After 2 to 4 weeks
      recovery from 8, 12, and 19 weeks of gossypol treatment, NPE-RPS failed to shift
      four bands (b through e) in site 1. These results suggested that gossypol
      treatment affected the transcription factors for interaction with site 1. On the
      contrary, no effect was demonstrated in NPE that interacted with site 2.
      Furthermore, gossypol treatment did not change the nucleotide sequence in the
      H4GP site 1 and 2.

PMID- 8536452
TI  - Decline in cerebral thromboembolism among young women after introduction of low
      dose oral contraceptives: an incidence study for the period 1980-1993.
AB  - The aim of this study was to analyze age-specific incidence rates (IRs) of
      cerebral thromboembolic attacks (CTA) among women and men 15-44 years of age in
      Denmark from 1980 through 1993 and to quantify possible influences from oral
      contraceptives (OC) on the incidence figures. The discharge diagnoses ICD 432-436
      from all Danish neurological, neurosurgical and medical departments during the
      period 1980-1993 were identified in a central diagnosis register. The use of OC
      was achieved from complete sale statistics during the study period and cross
      sectional studies assessing the type-specific use of OC at different ages. During
      the 14-year study period, 2,100 female and 2,552 male attacks were registered.
      Men had an exponentially increasing IR with increasing age. Compared with men in
      the period 1980-86, women had more attacks in the 20-35-year age group and fewer
      attacks above the age of 35. After 1987 the sex differences below the age of 35
      were not significant. From the first half (1980-86) to the last half (1987-1993)
      of the study period, women below 30 years had a significantly falling CTA IR of 
      20.4%, compared with a non-significant fall of -9.5% among men below 30 years. In
      the age group above 30 years, women experienced a not significant increase of
      4.2%, men a significant increase of 11.4%. Assuming that use of OC implied an
      average relative risk of CTA 111115 and pregnancy a relative risk of 4, a
      correction was made for the contribution of incident cases among women. (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8536453
TI  - Past contraceptive method use and risk of ectopic pregnancy.
AB  - The relationship between past contraceptive method use and risk of ectopic
      pregnancy has been analyzed in a case-control study conducted in Milan, Italy.
      Cases were 158 women with diagnosis of ectopic pregnancy confirmed by laparoscopy
      or laparotomy, admitted to a network of university and general hospitals of
      Milan. The first control group (obstetric controls) included 243 women who gave
      birth at term (more than 37 weeks' gestation) to healthy infants at the same
      hospitals where the cases had been identified. The second control group (non
      obstetric controls) was a random sample of 158 women admitted to the same network
      of hospitals where cases had been identified for diseases other than malignant,
      hormonal, or gynecological in origin. A total of 37 (23%) cases, 21 (9%)
      obstetric and 24 (15%) non-obstetric controls reported ever IUD use. The
      corresponding relative risk, RR, of ectopic pregnancy was 3.5 (95% CI 1.3-4.6)
      when non-obstetric subjects were considered as control group. The risk of ectopic
      pregnancy increased with duration of IUD use: in comparison with obstetric and
      non-obstetric controls, the RR were 2.3 and 2.0 for users for less than 2 years
      and 4.3 and 2.6 for longer users. There was no clear relation between time since
      last IUD use and risk of ectopic pregnancy, and no evidence of a decline of risk
      with increasing time since stopping use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536455
TI  - Effect of stromal inflammation on the outcome of limbal transplantation for
      corneal surface reconstruction.
AB  - Limbal transplantation (LT) is reportedly better than conjunctival
      transplantation in restoring rabbit corneal surfaces when performed 1-2 months
      (early stage) after severe damage. The outcome remains unclear if surgery is done
      at a later stage, and it is also unclear whether lamellar keratectomy should
      routinely be performed. Using the same rabbit model, LT was done at 3-4 months
      (intermediate limbal transplantation[ILT], n = 7) or 9-11 months (delayed limbal
      transplantation[DLT], n = 8) later. Lamellar keratectomy was also conducted with
      ILT in another group (keratectomy in intermediate limbal transplantation[IKLT], n
      = 7). External eye photography and fluorescein angiography were used to document
      corneal surface and stromal changes. The resultant epithelial phenotype was
      studied with AE-5 (cornea specific) and APSM-1/AM-3 (conjunctiva specific)
      monoclonal antibodies. As in previous studies of early limbal transplantation
      (ELT, performed at 1-2 months), ILT also had a high (eight of eight) success rate
      of restored corneal phenotype. In contrast, DLT yielded varying results: three of
      eight successes for corneal, three of eight for mixed, and two of eight for
      conjunctival phenotypes (p < 0.01, chi 2 trend). IKLT yielded four of seven
      corneal, two of seven mixed, and one of seven conjunctival phenotype successes.
      These results indicate that intense stromal inflammation associated with disease
      chronicity or additional stromal damage by lamellar keratectomy can interfere
      with the capability of limbal grafts to attain normal corneal epithelial
      proliferation and differentiation. Future studies of how limbal stem cells are
      regulated by the stromal environment are crucial to enhancing other clinical
      applications.

PMID- 8536454
TI  - Effectiveness of Norplant implants through seven years: a large-scale study in
      China.
AB  - The effectiveness of Norplant implants over a seven year period of continuous use
      was studied in a multicenter trial. Pregnancy rates were 0.4 per 100 in both year
      six and year seven. More than 3,600 women completed 6 years and more than 2,400
      women completed 7 years. Pregnancy rates increased with weight (p < .05) and
      decreased with age, but in years 6 and 7 combined, the pregnancy rate neither
      reached nor exceeded 1 per 100 woman years in any 5 year age group or in any 10
      kg weight group.

PMID- 8536456
TI  - T-cell repertoire of normal, rejected, and pathological corneas: phenotype and
      function.
AB  - The specific immune mechanisms of corneal graft rejection are not completely
      understood. Recently, the technique of growing T-cell lines from rejected
      allografts using recombinant IL-2 has enabled the cells involved in allograft
      rejection to be recognized. In the present study, this method was applied for the
      extraction and propagation of T lymphocytes from rejected, normal, and diseased
      corneas. T-cell lines could successfully be grown from rejected and normal
      corneas, but not from corneas with keratoconus or pseudophakic bullous
      keratopathy. The phenotypic repertoire of the grown cells was studied by FACS
      scan analysis. Rejected corneas were invaded by a mixture of activated CD4+ and
      CD8+ T-cell lines, with one population being predominant. In normal corneas only
      activated CD8+ cells with cytotoxic function were cultured. No cells were
      obtained from diseased corneas. The in vitro function of cell lines was assessed
      by primed lymphocyte testing. The present study shows that the technique of
      propagating invading T-cell lines from organ grafts can be applied to human
      corneas, offering a new approach to understanding the immunological mechanisms
      occurring inside this immune tissue.

PMID- 8536458
TI  - Corneal grafting of donor tissue preserved for longer than 4 weeks in organ
      culture medium.
AB  - In vitro viability of the endothelium of corneas stored in organ-culture medium
      is longer than in other storage techniques. This article reports on the clinical
      results of 20 penetrating keratoplasties performed using corneas stored for > 4
      weeks in organ culture. Seventeen of the procedures were elective and three were
      emergencies. Mean preservation time was 35.6 +/- 7 days (mean +/- SD) and mean
      follow-up was 16.2 months. During preservation, an endothelial cell loss of 10%
      was noted. Seventeen grafts remained transparent, and three failed between 3 and
      24 months postoperatively. Mean endothelial cell density was 2,153 +/- 372/mm2 at
      4 months and 1,854 +/- 390/mm2 at 12 months. Central pachymetry was 548 +/- 53
      microns at 4 months and 528 +/- 57 microns at 12 months after surgery. Corneas
      stored for up to 48 days in organ culture can be used in elective as well as in
      emergency procedures.

PMID- 8536457
TI  - Positive donor rim culture in penetrating keratoplasty.
AB  - A 3-year retrospective study on the risk factors of positive donor rim cultures
      in penetrating keratoplasty was performed. One thousand and ninety-seven
      consecutive donor rim cultures were reviewed from the period between June 1990
      and October 1993 to determine the rate of culture positivity. The sex, age,
      diabetes status, use of respirator at time of death, cause of death, harvesting
      technique, storage time, and corneal storage medium utilized for the donors with
      positive donor rim culture were compared to those for 100 randomly selected
      culture negative donor controls. Logistic analysis was performed to eliminate
      confounding effects. Forty-six of the 1,097 (4.19%) donor rim cultures were
      positive. We found an association between the in situ technique for donor
      harvesting and culture negativity (p = 0.03). None of the other donor
      characteristics was associated with culture positivity. None of the 46 recipients
      who received the positive culture corneas developed endophthalmitis. In situ
      cornea harvesting promotes less contamination than enucleation and enriched
      gentamicin and streptomycin storage medium may further decrease donor rim culture
      positivity.

PMID- 8536459
TI  - Confocal microscopy of corneal graft rejection.
AB  - Corneal allografts were transplanted into inflamed and vascularized graft beds in
      rabbit eyes. The grafts were examined every 4 days by slit-lamp biomicroscopy and
      scanning confocal microscopy. Confocal images were recorded with a video camera
      and computer enhanced in real-time. Layers of the cornea were visualized in
      serial optical sections parallel to the epithelium. In the third postoperative
      week, signs of graft rejection were observed; slit-lamp examination revealed a
      circumferential line of epithelial rejection, along with cloudiness and edema.
      Vessels were observed growing into the graft. By confocal microscopy,
      infiltrating cells were seen in the graft stroma. Foci of cells were especially
      pronounced around the sutures. Scattered leukocyte infiltrates were prominent at
      capillary terminals. There was an accompanying reduction in the stromal
      keratocyte density in the region of the infiltrate. Additionally, various degrees
      of fibrosis were noted around each suture and at the host-graft interface.
      Confocal microscopy may provide a valuable clinical tool for determining the
      earliest indicators of an antigraft immune response, and as an aid in the
      differential diagnosis of other inflammatory conditions of the cornea.

PMID- 8536460
TI  - Transplantation of preserved human amniotic membrane for surface reconstruction
      in severely damaged rabbit corneas.
AB  - After n-heptanol removal of the total corneal epithelium and a limbal lamellar
      keratectomy, 23 rabbit eyes developed features of limbal stem cell deficiency
      including conjunctival epithelial ingrowth, vascularization and chronic
      inflammation. One month later, 10 control eyes received a total keratectomy, and
      13 experimental eyes received additional transplantation of glycerin-preserved
      human amniotic membrane. In 3 months of follow-up, all control corneas were
      revascularized to the center with granuloma and retained a conjunctival
      epithelial phenotype. In contrast, five corneas in the experimental group became
      clear with either minimal or no vascularization; the rest had either mid
      peripheral (n = 5) or total (n = 3) vascularization and cloudier stroma. The
      success of corneal surface reconstruction correlated with the return of a cornea
      like epithelial phenotype and the preservation of amniotic membrane, whereas the
      failure maintained a conjunctival epithelial phenotype and the amniotic membrane
      was either partially degraded or covered by host fibrovascular stroma. These
      results suggest that measures taken to facilitate epithelialization without
      allowing host fibrovascular ingrowth onto the amniotic membrane might prove this
      procedure clinically useful for ocular surface reconstruction.

PMID- 8536461
TI  - Clinical evaluation of corneal epithelial barrier function with the slit-lamp
      fluorophotometer.
AB  - We designed a simple and quantitative method for the clinical evaluation of
      corneal epithelial barrier function using a slit-lamp fluorophotometer and
      applied it to healthy volunteers and dry-eye patients. The fluorophotometric
      method used was as follows: Three microliter of 0.5% fluorescein solution was
      applied to the cornea in the untouched fashion. Ten minutes after instillation,
      the ocular surface was washed. Twenty minutes afterward, corneal fluorescence
      intensity was measured and converted into fluorescein concentration. Corneal
      condition was classified into four grades: no superficial punctate keratopathy
      (SPK) anywhere on the cornea (grade 0); no SPK at the central cornea (grade 1),
      mild SPK at the central cornea (grade 2), and severe SPK at the central cornea
      (grade 3). In the volunteers, corneal condition was classified as grade 0 and
      fluorescein uptake (ng/ml) was 22.4 +/- 16.9 (mean +/- SD, n = 86). In dry eye,
      fluorescein uptakes showed significant increase in accordance with SPK severity:
      grade 1: 96.4 +/- 51.2 (n = 13); grade 2: 318.6 +/- 146.0 (n = 11); and grade 3:
      1479.1 +/- 671.9 (n = 10) (each p < 0.0005). This simple method with the slit
      lamp fluorophotometer can be used for the clinical grading of SPK in dry eye or
      other ocular surface diseases.

PMID- 8536462
TI  - Diltiazem spares corneal A delta mechano and C fiber cold receptors and preserves
      epithelial wound healing.
AB  - Recent interest in the corneal analgesic properties of diltiazem prompted the
      present study examining concentration-dependent effects of this calcium channel
      blocker on C fiber cold receptors and A delta mechanoreceptors. Both afferent
      fiber types mediate an eye blink reflex, important for protecting the corneal
      surface. The effects of neuroactive concentrations of diltiazem on corneal would
      healing were also studied. An in vitro rabbit cornea preparation was used for
      both electrophysiological recording and wound healing, allowing precise
      concentration-response analysis. Diltiazem produced a concentration-dependent
      depression of cold fiber discharge activity (10 to 250 microM), but did not
      affect mechanoreceptor afferents. In addition, the broad spectrum Ca2+ channel
      blockers, Ni2+ and Cd2+, did not cause a significant reduction in A delta mechano
      or C fiber discharge activity. Diltiazem had no effect on corneal epithelial
      wound healing to a concentration of 50 microM. This is important if diltiazem is
      to be used for therapeutic control of pain following corneal injury or surgery,
      because sparing of the eye blink reflexes and wound healing are desirable
      properties for a corneal analgesic.

PMID- 8536463
TI  - Plasma membrane sialoglycoproteins of human corneal epithelium in culture.
AB  - A number of studies, using either rat or rabbit models, have focused on
      delineating the role of cell surface glycoconjugates in corneal epithelial cell
      migration and wound healing. We have recently identified the cell surface
      sialoglycoproteins of rabbit corneal epithelium and have shown that the levels of
      at least three membrane glycoproteins are markedly altered during cell migration.
      Because species-related differences may be present, it is important to select an
      appropriate animal model for studies designed to contribute to the understanding
      of the mechanism of human corneal wound healing. The purpose of this study was to
      identify the cell surface sialoglycoproteins of human corneal epithelium. Plasma
      membrane sialoglycoproteins of primary cultures of human corneal epithelium were
      labeled with NaB3H4 after oxidation by mild NaIO4 treatment. The labeled
      glycoproteins were analyzed by SDS-polyacrylamide gel electrophoresis and
      fluorography. Four different preparations of human corneal epithelial cell
      cultures were analyzed, and results were compared with those of rabbit corneal
      epithelium. Of the 11 radiolabeled sialoglycoproteins we identified recently in
      rabbit corneal epithelium, eight were also present in human corneal epithelium.
      These similarities in the electrophoretic patterns of the plasma membrane
      glycoproteins of the two species suggest that rabbit is most likely an
      appropriate animal model for studies designed to contribute to the understanding
      of the structure and function of cell surface glycoproteins of human corneal
      epithelium.

PMID- 8536464
TI  - Remarks on the vitality of the human cornea after organ culture.
AB  - The purpose of this study was to obtain further information on the viability of
      organ-cultured human cornea. We thus used a specific staining method for
      succinate dehydrogenase (SDH), which is located in the membrane system of vital
      mitochondria. We examined fresh and long-term-cultured human corneas. After an
      initial incubation period in dextran-free culture medium, corneas were stored in
      a medium containing dextran. With respect to different appearances of the SDH
      staining, minimal essential medium without dextran seems to have a positive
      effect on the condition of epithelial cells. After renewal of the medium,
      keratocytes showed a brief improvement followed by a delayed deterioration, while
      the endothelial cells were severely damaged. However, best results for all three
      cell types were observed on the fourth day in a medium containing dextran. We
      therefore conclude that these corneas were best suited for transplantation.

PMID- 8536465
TI  - Comparative cytoprotection of cultured corneal endothelial cells by water-soluble
      antioxidants against free-radical damage.
AB  - We reported previously that purpurogallin (PPG) markedly protects the cultured
      rabbit corneal endothelial cells (RCEC) against oxyradical damage generated with
      hypoxanthine (HX) and xanthine oxidase (XO)(1). In this study, we further
      compared the cytoprotective activities of PPG versus Trolox (TX, alpha
      tocopherol, a water-soluble analogue of vitamin E) and ascorbate (Asc) in
      confluent cultured RCEC with phase contrast microscopy and confirmed by
      transmission electron microscopy. PPG prolonged survival of the oxyradical
      damaged cells longer than those without PPG present (18.6 +/- 1.4 min at 1.0 mM
      and 11.2 +/- 1.0 at 0.25 mM respectively vs. 7.3 +/- 0.8 min in control). At
      levels equimolar to PPG, TX, and Asc were less effective in delaying cell
      necrosis caused by HX and XO (p < 0.01). When exposed to superoxide radicals
      generated by menadione, RCEC necrosed at 29.8 +/- 1.5 min compared to PPG 47.2 +/
      1.0 min at 1.0 mM and 38.9 +/- 1.0 min at 0.25 mM. This was significantly
      different from TX and Asc at corresponding concentrations (p < 0.01). PPG
      scavenges not only HX-XO-generated oxyradicals, but also nonenzymatically
      produced superoxide radicals, more actively than two well known antioxidants--TX
      and Asc.

PMID- 8536466
TI  - Standardization of conjunctival impression cytology.
AB  - Lack of standardization limits the potential of conjunctival impression cytology
      as a clinical and research tool. This may be attributed to the variety of filter
      paper currently used. MF Millipore membrane filters of pore sizes 8.0, 3.0, 0.45,
      0.22, and 0.025 micron were tested. Samples obtained from 30 eyes of rabbits were
      randomized and scored by four masked observers for cellularity and morphologic
      preservation. Cellularity was significantly greater with pore sizes 8.0, 3.0, and
      0.45 micron versus 0.22 and 0.025 micron (p < or = 0.001), with an 83%
      correlation among four scorers. In contrast, morphology was better preserved in
      the smaller pore size papers (0.22 and 0.025 micron) when compared with larger
      pore sizes (p = 0.048). Using the best two filter papers (0.22 and 0.025 micron)
      and an ophthalmodynamometer, either 40, 60, or 80 g of pressure was applied for 3
      s to each pore size paper to see whether cellularity could be increased.
      Cellularity was greater with pore size 0.22 than 0.025 micron (42.3 +/- 19.8
      versus 8.7 +/- 6.4). Regardless of the pore size of the filter paper, cellularity
      was significantly improved at 60 g when compared with either 80 or 40 g. The
      results show that to maximize cell acquisition, a paper with medium pore size
      (0.22 micron) and a pressure of 60 g may be the best choice.

PMID- 8536467
TI  - Chlamydia trachomatis can be transmitted by a nonporous plastic surface in vitro.
AB  - Chlamydial conjunctivitis is a disease associated with venereal transmission
      through direct sexual contact or autoinoculation with genital secretions.
      Appropriate therapy for patients and their sexual partners involves important
      questions regarding the source of infection and mode of transmission. This study
      explored the potential role of a fomite, i.e., an environmental surface, as a
      possible vector of transmission. We determined the in vitro recovery of Chlamydia
      trachomatis from a nonporous plastic surface under ambient and humid conditions
      using the standard shell vial technique and confirmation by direct monoclonal
      immunofluorescence. Under ambient conditions, the TP50 (time at which 50% of
      samples were positive for Chlamydia) was 5 min, with complete desiccation
      occurring at 45 min. Under humid conditions, the TP50 was 52.5 min and complete
      desiccation did not occur up to 3 h. Beyond 45 min, a significantly greater
      number of positive chlamydial samples were collected under humid conditions (11
      of 30) than under ambient conditions (0 of 30) (p = 0.00016). We conclude that a
      fomite, such as a nonporous plastic surface, may serve as a potential vector for
      the transmission of chlamydial infection to the eye, especially under humid
      conditions. This new information may prove useful in counseling patients and
      their sexual partners.

PMID- 8536468
TI  - Topographic analysis of the changes in corneal shape due to aging.
AB  - We studied the aging changes in corneal shape using corneal topography. Normal
      corneas (1,343) from 734 volunteers were examined by Topographic Modeling System
      1 (TMS-1). All eyes were divided into eight groups according to age: (a) < 20
      years of age and, respectively, in their (b) 20s, (c) 30s, (d) 40s, (e) 50s, (f)
      60s, (g) 70s, and (h) > 80. The age-related changes in the averaged map of TMS-1
      were evaluated. The findings noted in this map were confirmed by analyzing the
      data as well as by assessing the average-of-difference map. The averaged maps of
      subjects from < 20 years of age to the 40s showed a vertical bow-tie-rule
      astigmatism. In the maps of subjects in their 50s and 60s, the central steep area
      gradually extended horizontally until it became a round configuration. The maps
      of subjects in their 70s and > 80 revealed a horizontal oval-shaped steep area,
      suggesting against-the-rule astigmatism. The average-of-difference map
      demonstrated a marked corneal steepening at the horizontal meridians. In the data
      analysis of the averaged map, the mean refractive powers of the cornea increased
      with age. Moreover, the refractive powers in the horizontal meridians exceeded
      those in the vertical meridians when they were in the 60s, which verified against
      the-rule astigmatic shift. In conclusion, normal cornea becomes steeper and
      shifts from with-the-rule to against-the-rule astigmatism with age.

PMID- 8536469
TI  - Capnocytophaga ochracea chronic blepharoconjunctivitis.
AB  - A 70-year-old woman presented with a 10-month history of chronic
      blepharoconjunctivitis that had been unresponsive to multiple methods of
      treatment. The patient was not immunocompromised and had no history of corneal
      disease, ocular trauma, or lacrimal duct obstruction. Gram and Giemsa staining of
      conjunctival smears resulted in visualization of slender, fusiform bacilli.
      Culture of conjunctival scrapings led to the recovery of a fastidious isolate
      identified as Capnocytophaga ochracea. The same microorganism was also recovered
      from cultures of the patient's gingiva. The blepharoconjunctivitis responded well
      to treatment with fortified cefazolin eye drops. Awareness of this easily
      overlooked bacterial species should prompt the use of smear and cultural
      techniques.

PMID- 8536470
TI  - Mycobacterium chelonae keratitis: resolution after debridement and presoaked
      collagen shields.
AB  - We report a case of Mycobacterium chelonae keratitis following corneal injury by
      a foreign body. Diagnosis was made by Ziehl-Neelsen staining and Lowenstein
      Jensen culture of corneal scrapings. On the basis of the in vitro susceptibility
      testing, the patient was treated with topical fortified amikacin. Given the lack
      of response to this therapy, we decided to carry out a debridement of the
      infiltrative areas to eliminate infected tissue, and to use an amikacin-soaked
      collagen shield supplemented every 4 h with topical fortified amikacin to promote
      healing of the debrided area and to potentiate the effects of the antibiotic
      therapy. After this treatment, clinical resolution was observed and a further
      acid-fast stain and culture for mycobacterium were negative. Debridement of the
      infiltrative areas could be used in cases of mycobacterium keratitis when early
      diagnosis is made and before the corneal infection has become widespread.

PMID- 8536471
TI  - Epithelial iron line in juvenile corneal arcus lipoides.
AB  - Iron lines of the corneal epithelium are well-described phenomena in both normal
      and pathologic conditions. We found a bilateral corneal epithelial iron line at
      the inner edge of a juvenile corneal arcus lipoides in an otherwise normal eye of
      a 38-year-old white man. Possible mechanisms that may have led to the development
      of this new iron line are discussed.

PMID- 8536472
TI  - Etiopathology of pinguecula and pterigium.

PMID- 8536473
TI  - Memory and skill acquisition in Parkinson's disease and frontal lobe dysfunction.
AB  - Animal experiments and human neuropsychological studies have provided evidence
      for the hypothesis that skill acquisition may be regulated by the basal ganglia.
      In the present studies, perceptual and cognitive skill acquisition as well as a
      number of explicit verbal memory functions were investigated in patients in early
      and more advanced stages of Parkinson's disease (PD) and in patients with frontal
      lobe lesions. Patients in more advanced stages of PD were impaired at cognitive
      skill acquisition as well as during recall conditions that involved active
      semantic organisation of the stimulus material. Similar explicit memory deficits
      were present in frontally lesioned patients. PD patients with unilateral symptoms
      showed a selective impairment in acquiring a cognitive skill. Perceptual skill
      acquisition was preserved in all groups. The overall pattern of memory impairment
      in PD is largely consistent with dysfunction of fronto-striatal circuitry.

PMID- 8536474
TI  - Selective impairment for simple division.
AB  - We report the case of a patient, C.B., with a calculation impairment. His
      performance on simple division problems was severely impaired while his
      performance on simple and complex addition, subtraction and multiplication
      problems was largely spared. The patient was also found to be impaired in solving
      simple arithmetical problems such as Nx? = M. The implications of these findings
      for the organization of arithmetical facts are discussed.

PMID- 8536475
TI  - Temporal and spatial processing in reading disabled and normal children.
AB  - The ability to process temporal and spatial visual stimuli was studied to
      investigate the role these functions play in the reading process. Previous
      studies of this type have often been confounded by memory involvement, or did not
      take into account the evidence which suggests a visual transient deficient in
      some dyslexics. Normal (n = 39), reading disabled (n = 26), and backward reading
      children (n=12) were compared on a visual computer game, which consisted of a
      temporal and a analogous spatial dot counting task. Reading disabled children
      performed significantly worse than normal children on the Temporal Dot Task, but
      were only mildly impaired on the Spatial Dot Task, Backward readers were not
      significantly better than the reading disabled group on either task, suggesting
      that poor poor visual temporal processing is not specific to dyslexia. In a group
      of 93 children, a regression model including age, verbal IQ, phonological
      awareness, and visual temporal processing ability, predicted 73% of the variance
      of reading ability. The results suggest that dyslexics perform worse in tasks
      that require fast, sequential processing and that this impairment may be
      partially responsible for their reading difficulties.

PMID- 8536476
TI  - The role of the output phonological buffer in the control of speech timing: a
      single case study.
AB  - A patient with a selective impairment of speech output, associating phonemic
      paraphasias and pervasive preverbal pauses, it is described. Experimental data
      are discussed in relation to current models of speech production. On clinical
      evaluation, the pattern of paraphasias was strongly suggestive of a functional
      lesion affecting the output phonological buffer. This hypothesis received
      substantial support from a study of word and non-word repetition, as well as from
      a study of picture naming latencies, with various imposed delays between stimulus
      presentation and vocal response. In order to determine the origin of the
      preverbal pauses, the patient was also submitted to other timed motor tasks
      implicity probing higher levels of word production (gender decision and phonemic
      matching). We suggest that the pauses probably resulted from the conjunction of
      several mechanisms, including a general slowing apparent in all timed motor
      tasks, as well as a more specific time lag in speech initiation originating from
      the output buffer or from the articulator itself.

PMID- 8536477
TI  - The role of visual discrimination disorders and neglect in perceptual
      categorization deficits in right and left hemisphere damaged patients.
AB  - This study was designed to investigate the role of visual sensory deficits and
      neglect in perceptual categorization deficits in a group of 35 patients with
      unilateral cerebral lesions. From theoretical point of view, it was expected that
      right hemisphere lesions would play a critical role in eliciting perceptual
      categorization deficits which could not be accounted for by visual sensory
      deficits or neglect. The results revealed that perceptual categorization deficits
      were not confined to RHD patients, but they were also found in LHD patients. RHD
      patients were impaired regardless of the nature of the task (verbal vs.
      nonverbal), while LHD patients were impaired on nonverbal tasks, and in a lesser
      degree on verbal tasks. In both braindamaged groups, perceptual categorization
      deficits were highly associated with visual sensory deficits, however, perceptual
      categorization deficits were also found without impairments in the visual sensory
      system. Neglect to be less important determinant of perceptual categorization
      deficits. The present findings are discussed in the light of Warrington's model
      of object agnosia.

PMID- 8536478
TI  - Is there really a syndrome involving the co-occurrence of neurodevelopmental
      disorder talent, non-right handedness and immune disorder among children?
AB  - This paper is the first large-scale attempt to test Geschwind and Galaburda's
      (1985a, 1985b, 1985c) hypothesis that there should be a four-way association
      among neurodevelopmental disorders (NDs), special talents, non-right handedness,
      and immune disorders. In a sample of 11,578 children, several two-way
      associations were found, but not those most strongly predicted by the theory. For
      example, non-right handedness was not associated with NDs considered to be
      secondary to left hemisphere dysfunction (e.g., articulation disorder, reading
      disability, verbal aptitude deficits). Instead, non-right handedness was
      associated with NDs that involve generalized brain damage (e.g. cerebral palsy,
      mental retardation, and seizures). One immune disorder (asthma) was associated
      with one ND (attention deficit disorder); immune disorder was not associated with
      non-right handedness. Less than 1% of this sample manifested the co-occurrence of
      any three or four of these markers. In sum, there was little evidence in support
      of the syndrome suggested by Geschwind and Galaburda (1985a, 1985b, 1985c).

PMID- 8536479
TI  - Covert face recognition in prosopagnosia: a dissociable function?
AB  - Covert face recognition was investigated in a patient with prosopagnosia without
      object agnosia. This patient performed well in various face processing tasks like
      expression analysis and feature processing and had relatively preserved semantic
      knowledge about persons, but was slightly impaired in the visual matching of
      unfamiliar faces. In face-name paired-associate relearning task, covert face
      recognition was demonstrated to be above-chance. However, as this task cannot be
      meaningfully applied to control subjects, results do not necessarily indicate
      that the degree of covert face recognition is normal. In fact, in contrast to
      control subjects, the patient showed significantly reduced associative priming of
      names by face primes as compared to name primes, suggesting a quantitative
      reduction of covert face recognition. It is argued that these results support the
      view that overt and covert face recognition are brought about by the same
      functional system (Farah, O'Reilly and Vecera, 1993).

PMID- 8536480
TI  - Persistent retrograde, amnesia following a minor trauma.
AB  - A 19-year-old man showed dense retrograde amnesia (RA) for autobiographical and
      public events covering his entire life, following a motor car accident that
      caused no apparent brain damage. His learning abilities remained excellent and
      permitted him to recover knowledge of the past, based on information gathered
      from other people and the media, although he never reacquired the sense of
      personal experience. At the onset he also showed occasional gaps in his semantic
      memory, e.g., he failed to recognize a few objects and was unable to provide
      factual information about sports he had long been playing. Eventually, his
      amnesia was predominantly restricted to autobiographical events or facts. After
      29 months the deficit has remained unchanged. CT, MRI and PET were negative.
      Psychogenic amnesia was considered, but eventually ruled out for want of any
      evidence pointing to emotional problems, stressful situations or secondary gains.
      We posit that for reasons unknown a mild trauma can cause functional inhibition
      of the access to the engrams that are already stored, leaving intact the ability
      to encode and retrieve new memories.

PMID- 8536481
TI  - Maternal age and parity correlates of handedness: gender, but no parental
      handedness modulation of effects.
AB  - Mothers supplied information on the handedness of a total of 1079 children (238
      left handed, 841 right handed), and also reported information on the handedness
      of the biological parents, parental ages when each child was born, parity, and
      birth complications. A MANOVA, employing offspring handedness and parental
      handedness (presence versus absence of at least one left handed) as the bases of
      classification, and parity, maternal age, paternal age, and a birth stress
      composite score as dependent measures, was applied to the data of female and male
      offspring separately. For females, there was a significant multivariate effect
      for handedness, but no effect of parental handedness nor any interaction of the
      handedness and parental handedness factors. Univariate ANOVAs, following the
      multivariate analysis, showed significant effects of handedness for the maternal
      age and parity measures, but not for paternal age or birth stress composite
      score. The analysis for males showed no significant multivariate or univariate
      effects. The data suggest, that in the absence of high risk parity and maternal
      age over 32, only about 7.8% of females are left handed. This implies that as
      many as 29% or so of female left handers may owe their sinistrality to factors
      associated with high risk parity and maternal ages over 32.

PMID- 8536482
TI  - Fornix damage and memory. A case report.
AB  - The role of the fornix for episodic memory processing is still a matter of
      controversy. A juvenile patient of average post-surgical intelligence with
      fornical damage due to tumor removal is described. The fornix was damaged
      bilaterally at the level of the fornical columns. The patient thereafter suffered
      major anterograde amnesia which was most pronounced in tests using long delays
      (e.g., in the delayed recall index of the revised Wechsler Memory Scale). Amnesia
      was a prominent on the verbal as on the nonverbal level. Attention, concentration
      and short term memory abilities were preserved. Cognitive flexibility, procedural
      memory and priming were principally unimpaired. There was no evidence of
      retrograde amnesia. It is concluded that the fornix constitutes a major link
      between the three memory interfaces (medial diencephalon, medial temporal lobe,
      basal forebrain) and that its bilateral rupture anterior to the thalamic level
      may lead to lasting anterograde amnesia.

PMID- 8536483
TI  - Auditory cerebral lateralization following cross-gender hormone therapy.
AB  - In this study, 10 men, 10 women, and 13 genetic male transsexuals, all of them
      righthanded, were tested on two verbal (CV and nonsense polysyllables) and two
      nonverbal (melodies and triple tone [3T]) dichotic tasks to investigate relations
      between hormone therapy and auditory cerebral specialization for speech and non
      speech stimuli in adults. At time of testing, all transsexuals had been made
      under hormonal treatment for at least one year and eight had had corrective
      surgery. ANOVA results showed a right ear advantage and similar pattern of
      performance for the three groups in the treatment of speech. In nonverbal tasks,
      interactions revealed a left ear advantage in the processing of melodies and 3T
      for men only: women and transsexuals exhibited similar performance in both
      nonverbal tasks. In accord with generalization from the animal literature,
      cautious interpretation of the data is some possible hormonal involvement, in
      adults, in the modulation of right hemispheric cognitive processing.

PMID- 8536484
TI  - Selective impairment of the retrieval of people's names: a case of category
      specificity.
AB  - Recent cases of 'proper names anomia' have been interpreted as arising from a
      category-specific recall deficit that is mediated either by the effects of
      'uniqueness', or 'meaningfulness'. However, an alternative account is suggested
      by the report of a patient whose difficulties in naming familiar people arise
      from a selective learning impairment. The current case study presents data that
      are inconsistent with a learning interpretation of difficulties in naming people.
      We conclude that a dissociation exists between selective deficits affecting the
      learning and recall of people's names.

PMID- 8536485
TI  - Impaired naming and preserved reading: a complete dissociation.
AB  - This study examines the relationship between reading and naming in an anomic
      patient whose verbal comprehension skills were intact. In spite of very poor
      naming skills, his ability to read irregular words was well preserved. Moreover,
      his naming remained impaired in conditions when he had read the same word only a
      few minutes or even seconds before and there was unexpectedly little overlap
      between his performance on the two tasks. The implications of these results for
      current models of reading and naming are discussed.

PMID- 8536486
TI  - Vestibular stimulation, spatial hemineglect and dysphasia, selective effects.
AB  - The selectivity of the effects of vestibular stimulation was investigated in a
      left brain-damaged patient suffering from right visuo-spatial hemineglect and
      severe dysplasia. Vestibular stimulation temporarily improved the former but not
      the latter disorder. These results support the view that this treatment improves
      hemineglect by a specific effect, running counter the rightward distortion of
      egocentric co-ordinates, rather than by a general hemispheric activation.

PMID- 8536487
TI  - Congenital uterine malformations.
AB  - With the advent of newer imaging techniques, the radiologist is now able to make
      very precise and accurate diagnoses of congenital uterine malformations and their
      complications. Because these anomalies are associated with reproductive
      dysfunction, they are often discovered during an infertility evaluation. By
      imaging parallel to the long axis of the uterus, the external contour can be
      evaluated, obviating laparoscopy for differentiating septate from bicornuate
      uteri. Obstructed uterovaginal anomalies (e.g., hematometros, hematometrocolpos),
      an important complication of abnormal mullerian duct development, can occur at
      any time from the newborn period to adulthood. Determining the site of
      obstruction is imperative for planning the proper surgical approach. To
      understand these malformations better, we review the relevant embryology. The
      most widely accepted classification scheme is discussed in detail, with an
      emphasis on diagnosis, prognosis, and therapeutic options.

PMID- 8536488
TI  - Gastroesophageal reflux in childhood.
AB  - Gastroesophageal reflux (GER) is one of the most frequent symptomatic clinical
      disorders affecting the gastrointestinal tract of infants and children. During
      the past 2 decades, GER has been recognized more frequently because of an
      increased awareness of the condition and also because of the more sophisticated
      diagnostic techniques that have been developed for both identifying and
      quantifying the disorder. Gastroesophageal fundoplication is currently one of the
      three most common major operations performed on infants and children by pediatric
      surgeons in the United States. Normal gastroesophageal function is a complex
      mechanism that depends on effective esophageal motility, timely relaxation and
      contractility of the lower esophageal sphincter, the mean intraluminal pressure
      in the stomach, the effectiveness of contractility in emptying of the stomach,
      and the ease of gastric outflow. More than one of these factors are often
      abnormal in the same child with symptomatic GER. In addition, in patients with
      GER disease, and particularly in those patients with neurologic disorders, there
      appears to be a high prevalence of autonomic neuropathy in which esophagogastric
      transit and gastric emptying are frequently delayed, producing a somewhat complex
      foregut motility disorder. GER has a different course and prognosis depending on
      the age of onset. The incompetent lower esophageal sphincter mechanism present in
      most newborn infants combined with the increased intraabdominal pressure from
      crying or straining commonly becomes much less frequent as a cause of vomiting
      after the age of 4 months. Chalasia and rumination of infancy are self-limited
      and should be carefully separated from symptomatic GER, which requires treatment.
      The most frequent complications of recurrent GER in childhood are failure to
      thrive as a result of caloric deprivation and recurrent bronchitis or pneumonia
      caused by repeated pulmonary aspiration of gastric fluid. Children with GER
      disease commonly have more refluxing episodes when in the supine position,
      particularly during sleep. The reflux of acid into the mid or upper esophagus may
      stimulate vagal reflexes and produce reflex laryngospasm, bronchospasm, or both,
      which may accentuate the symptoms of asthma. Reflux may also be a cause of
      obstructive apnea in infants and possibly a cause of recurrent stridor, acute
      hypoxia, and even the sudden infant death syndrome. Premature infants with
      respiratory distress syndrome have a high incidence of GER. Esophagitis and
      severe dental carries are common manifestations of GER in childhood. Barrett's
      columnar mucosal changes in the lower esophagus are not infrequent in adolescent
      children with chronic GER, particularly when Heliobacter pylori is present in the
      gastric mucosa. Associated disorders include esophageal dysmotility, which has
      been recognized in approximately one third of children with severe GER.
      Symptomatic GER is estimated to occur in 30% to 80% of infants who have undergone
      repair of esophageal atresia malformations. Neurologically impaired children are
      at high risk for having symptomatic GER, particularly if nasogastric or
      gastrostomy feedings are necessary. Delayed gastric emptying (DGE) has been
      documented with increasing frequency in infants and children who have symptoms of
      GER, particularly those with neurologic disorders. DGE may also be a cause of gas
      bloat, gagging, and breakdown or slippage of a well-constructed gastroesophageal
      fundoplication. The most helpful test for diagnosing and quantifying GER in
      childhood is the 24-hour esophageal pH monitoring study. Miniaturized probes that
      are small enough to use easily in the newborn infant are available. This study is
      100% accurate in diagnosing reflux when the esophageal pH is less than 4.0 for
      more than 5% of the total monitored time.

PMID- 8536489
TI  - Coexistence of subacute cutaneous lupus erythematosus and porphyria cutanea
      tarda: a case report.
AB  - We report a case of coexisting cutaneous lupus erythematosus and porphyria
      cutanea tarda in an alcoholic outdoorsman. We discuss the therapeutic dilemmas
      encountered and eventual treatment approach: sunscreens, topical corticosteroids,
      alcohol abstinence, and phlebotomy.

PMID- 8536490
TI  - Ecchymotic Kaposi's sarcoma.
AB  - We report two patients with ecchymotic patches that did not suggest the diagnosis
      of Kaposi's sarcoma. The principal complaint of one patient was facial and
      periorbital edema with bilateral periorbital ecchymosis. On his trunk were
      patches resembling pityriasis rosea-like Kaposi's sarcoma. Both types of lesions
      proved to be Kaposi's sarcoma on histologic examination. The second patient had
      scattered ecchymotic lesions, with typical lesions of Kaposi's sarcoma elsewhere
      on his body. The ecchymotic lesions showed a large amount of extravasated red
      blood cells and no evidence of amyloid. This variant has not been described
      previously to our knowledge.

PMID- 8536491
TI  - Stroke-induced purpura in lesions of colloid milium.
AB  - We describe three patients with colloid milium whose lesions showed purpura upon
      stroking. Two of these patients had juvenile colloid milium and the third had
      adult colloid milium. Ultramicroscopic examination of purpuric colloid papules
      showed that the dermal blood vessel walls were infiltrated by colloid material.
      Traumatic purpura occurring in colloid milium may be analogous to that occurring
      in systemic amyloidosis. We suggest that the infiltrating colloid material
      decreases the elasticity of dermal blood vessel walls, accounting for the purpura
      following minor trauma.

PMID- 8536492
TI  - The new female and male polyurethane condoms.

PMID- 8536493
TI  - How to use topical tretinoin in treating acne.

PMID- 8536494
TI  - A dermatologic diary. Portrait of a practice.

PMID- 8536495
TI  - Spontaneous improvement of a port wine stain.
AB  - A 3-year-old child had been born with an extensive vascular lesion that was
      clinically and histologically consistent with a port wine stain. Between the ages
      of six months and three years the lesion showed a remarkable degree of
      spontaneous resolution. This degree of improvement is exceptional after the age
      of six months and is documented photographically in this report.

PMID- 8536496
TI  - Primary cutaneous Cryptococcus in nonimmunocompromised patients.
AB  - Cutaneous cryptococcosis in the nonimmunocompromised host is a rare entity and,
      when it does occur, presents with protean manifestations making a clinical
      diagnosis difficult. The diagnosis is made by a combination of a high degree of
      suspicion, clinical features, and histopathologic examination of the skin biopsy.
      Antifungals should be used early in the disease; however, the class of
      antifungal, dose, and duration of therapy is controversial at this time.

PMID- 8536497
TI  - Assessment and exercise in low back pain. With special reference to the
      management of pain and disability following first time lumbar disc surgery.
AB  - Eight articles including 555 low back pain patients have been published. They
      included the following topics: 1) A ratio interval rating scale (Low Back Pain
      Rating Scale (RS)) was introduced. The possibility of registering the actual
      status in low back pain patients including; Back Pain, Sciatica, Functional
      Disability and Physical Impairment was studied. Methods of evaluating index
      scales developed in the field of psychometry were applied in the validation
      process of RS. RS was found to be both valid and user friendly. 2) Using Low Back
      Pain Rating Scale the general outcome following first-time lumbar disc surgery
      was analysed through a survey. The results showed that more than half of the
      patients still suffered from considerable Back Pain, Sciatica, and Functional
      Disabilities. Approximately 25% of the patients risked reduced work capabilities,
      and many receive pensions. 3) By means of a comprehensive statistical analysis of
      18 studied preoperative demographic and physical findings, sex, hypoalgesia,
      smoking and Finneson-index were found to have prognostic value. 4) Attempts at
      influencing the results obtained from lumbar disc surgery have been tested in 3
      randomized trials, including back training and peroperative glucocorticoid
      administration. 5) Three randomized trials including patients suffering from
      chronic low back pain (with or without previous lumbar disc surgery) attempted to
      convey which elements of a training programme provide patients with the greatest
      effect and the least risk of side-effects. It was concluded that Low Back Pain
      Rating Scale is a useable assessment instrument in both clinical trials and as a
      daily quality control instrument of back patients. There is a need of increased
      patient scrutiny in patient selection prior to lumbar disc surgery. Postoperative
      rehabilitation should include intensive back training, which has been shown to be
      of value in behavioural support and restoration of functional deficits. This has
      resulted in increased work capacities for disc operated patients. The exercise
      programmes are generally free of side-effects. As regards chronic back pain
      patients with or without previous lumbar surgery, high dosage exercises with
      training periods lasting at least 12 to 16 sessions are of crucial importance for
      success. Exercises should be dynamic and full-range, and carried out following
      the adage "Don't let the pain be your guide.

PMID- 8536498
TI  - Postoperative fatigue.

PMID- 8536499
TI  - Neuro-glial-immune interactions. An experimental, neural transplant and lesion
      study.

PMID- 8536500
TI  - The T cell receptor. Structural and functional studies.

PMID- 8536501
TI  - Evaluation of recombinant human growth hormone for wound management.

PMID- 8536502
TI  - Acute admissions to medical departments. A comparison between an urban and a
      rural district.
AB  - To compare hospitalization into medical departments, acute admissions into a city
      hospital and into a district hospital were compared prospectively over a two-week
      period. Patients referred to the city hospital were on average older, were more
      frequently living alone and they had a greater amount of social care attendance
      in their homes. On the other hand, distribution of referral diagnoses, overall
      patient activity, occupational status and contact with relatives were similar in
      the two areas. Sub-acute or acute illness was considered the main cause of
      admission in both areas; the amount of admissions for social reasons was 13
      percent to the city hospital versus 3 percent to the district hospital. Relevant
      alternatives to hospitalization seemed to exist in 50 percent of the admissions
      to the city hospital versus only 3 percent to the district hospital. Since
      patients admitted for social reasons block hospital beds for a longer time period
      than those admitted for other reasons, these differences may to some extent
      explain why length of hospital stay is longer in city hospitals than in rural
      ones.

PMID- 8536503
TI  - The Helicobacter pylori theory and duodenal ulcer disease. A case study of the
      research process.
AB  - OBJECTIVES: To describe the medical research process from the time of the
      generation of a new theory to its implementation in clinical practice. The
      Helicobacter pylori (H. pylori) theory, i.e. the theory that H. pylori plays a
      significant causal role in duodenal ulcer disease was chosen as a case. MATERIAL:
      Abstracts from 1984 to 1993, identified in the CD-Rom, Medline system,
      ("Silverplatter"), using the search terms Campylobacter pylori and Helicobacter
      pylori, and reviews and editorials about H. pylori in some of the most widespread
      clinical journals. RESULTS: 2204 papers on H. pylori were published, of which 64%
      (1,403) were original articles. Of these, 30% (415/1,403) were descriptive
      clinical studies, 5% (64) were epidemiological studies, 33% (459) were laboratory
      studies of disease mechanisms, 8% (112) were therapeutic intervention studies,
      and 24% (336) concerned diagnostic and therapeutic techniques. A total of 204 of
      the clinical studies addressed duodenal ulcer disease. Of these, 72% (147) were
      cross-sectional studies, 3% (7) were observational cohort studies and 25% (50)
      were therapeutic intervention studies. Thirty-one editorials and reviews
      concerning the etiological role of H. pylori in duodenal ulcer disease had been
      published in some of the most widespread clinical journals. In half of the papers
      the authors were convinced of the causal role of H. pylori in duodenal ulcer
      disease, while in the remainder they were sceptical. In seven cases the authors
      stated which patients should be selected for H. pylori eradication treatment.
      CONCLUSION: Descriptive clinical studies and laboratory studies of disease
      mechanisms were the prevailing types of research about H. pylori. Comparatively
      few therapeutic intervention studies were done; this fact may have hampered the
      acceptance of the H. pylori theory and the introduction of eradication therapy in
      clinical practice.

PMID- 8536504
TI  - Role of blood flow in protection against penetration of carcinogens into normal
      and healing rat gastric mucosa.
AB  - The effects of intragastric capsaicin and gastric artery ligation on the
      penetration of the gastric carcinogen N[methyl-3H]-N'-nitro-N-nitrosoguanidine
      ([3H]MNNG) to proliferative cells were studied in normal and healing rat gastric
      mucosa. The percentage of S-phase cells labeled with [3H]MNNG in normal corpus
      mucosa was higher (7.0 +/- 2.0%) after gastric artery ligation than in controls
      with intact blood flow (2.7 +/- 1.0%) and in animals treated with capsaicin (1.8
      +/- 0.5%). Corpus mucosal blood flow was correlated with the percentage of S
      phase cells labeled with [3H] MNNG in normal controls and in capsaicin-treated
      animals. In healing corpus mucosa and in the antrum, capsaicin or gastric artery
      ligation did not affect carcinogen penetration. We conclude that blood flow
      protects against penetration of carcinogens to proliferative cells in normal
      corpus mucosa but not in the antrum. Low mucosal blood flow in the corpus could
      be a risk factor for initiation of gastric carcinogenesis.

PMID- 8536505
TI  - A prospective study of upper gastrointestinal hemorrhage in patients with
      hepatocellular carcinoma.
AB  - Our purpose was to determine, in a prospective study, the causes of
      gastrointestinal hemorrhage in patients with hepatocellular carcinoma, and the
      relationship of portal vein invasion with variceal hemorrhage in these patients.
      During an 11-month period, 55 patients presented with hepatocellular carcinoma
      presented with signs and/or symptoms of upper gastrointestinal hemorrhage. Forty
      seven percent had bleeding from varices, whereas the majority, 53%, had a
      nonvariceal bleeding source. Among those with nonvariceal bleeding, duodenal
      ulceration was the commonest cause. Direct tumor invasion into the
      gastrointestinal tract was found in three patients. Tumor invasion of the portal
      venous system was detected by ultrasound examination in 76% of the variceal
      bleeders, compared to only 45% of the nonvariceal bleeders. Despite the very high
      frequency of cirrhosis among patients with hepatocellular carcinoma, the source
      of bleeding was variceal in less than half of the patients. Portal vein invasion
      is a risk factor for subsequent variceal bleed.

PMID- 8536506
TI  - Fecal alpha 1-antitrypsin detection of colorectal neoplasia. An evaluation using
      HemoQuant.
AB  - Fecal alpha 1-antitrypsin measurement may be of value for the detection of
      colorectal neoplasia and is compared with the HemoQuant test in 119 subjects with
      either a screen-positive Hemoccult result (N = 78) or iron-deficiency anaemia (N
      = 41). Nineteen patients were found to have colorectal cancer, 35 had colorectal
      adenomatous polyps, 5 had inflammatory bowel disease, and 60 had no detected
      cause of occult blood loss. Of the cancer patients, 63% (12/19) were detected by
      fecal alpha 1-antitrypsin and 63% (12/19) by HemoQuant. Of the adenomas > 1 cm in
      diameter 33% (7/23) were detected by fecal alpha 1-antitrypsin and 26% (6/23) by
      HemoQuant. There was a poor correlation between fecal alpha 1-antitrypsin and
      HemoQuant results for colorectal cancers (r = 0.37, P > 0.05), and combining the
      tests, the sensitivity for colorectal cancer was increased to 84% (16/19). Fecal
      protein loss, as measured using alpha 1-antitrypsin, appears to involve largely
      different mechanisms from that of blood loss from colorectal cancers.

PMID- 8536507
TI  - Establishment of a colonic polyp registry in Rhode Island.
AB  - A colonic adenomatous polyp registry (PR) has been organized at the Roger
      Williams Medical Center whose main functions are to prevent the occurrence of
      colorectal cancer (CRC) in the enrollees, to provide a population of subjects for
      epidemiological and interventional studies, and to provide educational, including
      dietary, information to subjects and physicians. One hundred four and 202
      patients with polyps, originally retrieved from the hospital pathology files,
      were enrolled in the 1984 and 1987 cohorts, respectively, of whom about 90% were
      followed for at least three years after polypectomy. Three carcinomas, all Dukes
      A, were found in the right colon in the follow-up period. New polyps identified
      in the first three years after polypectomy were generally small tubular adenomas
      with a greater predilection for the right colon than was found for the index
      polyps. Risk factors for new polyps included history of previous polyps and,
      probably, multiple index polyps. The use of colonoscopy for postpolypectomy
      surveillance increased between 1984 and 1987. About 25% of the subjects in each
      cohort were either lost to follow-up or received no endoscopic surveillance. On
      the other hand, some of those who were followed were probably subjected to
      excessive numbers of procedures. Defects in the PR include inadequacy of personal
      and family history data, and steady loss of patients during the three to six
      years after polypectomy. Despite the small size and limited resources of our
      hospital, its colonic polyp registry has already provided information that may
      help in the management of patients with this premalignant condition. The more
      widespread use of securely funded polyp registries would probably reduce the
      incidence of metachronous CRC in that population and would have significant
      epidemiological and educational functions.

PMID- 8536508
TI  - Morphometric analysis of intestinal mucins under different dietary conditions and
      gut flora in rats.
AB  - Elucidation of the mechanisms that alter the biosynthesis, turnover, and
      degradation of intestinal mucins is relevant to the understanding of both the
      normal gut ecosystem and various intestinal diseases. In this study image
      analysis was used to quantify the effects of diet and microbial flora on the
      mucin composition of goblet and deep crypt cells, the number and volume density
      of mucin-containing cells, and the staining density of their stored mucins in the
      small and large intestine of germ-free and conventionally maintained rats fed two
      different diets. One was a coarsely ground commercial rodent diet containing
      crude fiber of cereal origin and the other a purified diet composed of finely
      powdered ingredients, including cellulose as a source of fiber. The changes in
      mucin production were also analyzed in germ-free rats colonized with a human
      flora. Feeding a commercial diet reduced the volume density of cells containing
      neutral and sulfomucins in the jejunum of conventional rats and the staining
      density of neutral and acidic mucins in the germ-free rats. Both rat and human
      floras reduced the number of cells containing acidic and sulfomucins and the
      staining density of neutral mucins in the small intestine of animals fed on a
      purified diet. However, inoculation of human flora increased the staining density
      of stored neutral and sulfated mucins in the cells of the large intestine. The
      results demonstrate that the dietary changes are influential in modifying the
      amount and proportion of mucins in the small intestine and the microbial flora in
      the large intestine.

PMID- 8536510
TI  - Deficiency of water-soluble vitamins in Crohn's disease.

PMID- 8536509
TI  - Antilithiasic and hypocholesterolemic effects of diets containing autoclaved
      amylomaize starch in hamster.
AB  - The prevention of cholelithiasis by dietary manipulation was investigated in
      hamsters receiving a fat-free lithogenic (L) diet or this diet in which sucrose
      was replaced by 12 (group AS12), 36 (group AS36), 48 (group AS48), or 72.5%
      (group AS72.5) of autoclaved amylomaize starch for seven weeks. All hamsters
      (6/6) had cholesterol gallstones in groups L and AS12, while only 3/6 hamsters in
      group AS36 had gallstones. None were present in groups AS48 and AS72.5. Except in
      group AS12, biliary cholesterol level and lithogenic index (LI) decreased
      significantly in hamsters receiving amylomaize starch. Plasma cholesterol
      concentration was reduced by 31 and 54%, respectively, in groups AS48 and AS72.5
      as compared to group L. The concentration of esterified cholesterol in the liver
      was also reduced significantly in all groups receiving amylomaize starch. Hepatic
      cholesterogenesis was decreased by 74 and 65%, respectively, in groups AS48 and
      AS72.5 as compared to group L. The transformation of cholesterol to bile acids
      was increased in group AS72.5 (+152%) as compared to L, while fecal cholesterol
      excretion was strongly lowered (-31%). Amylomaize starch reduced the microbial
      transformation of cholesterol to coprosterol and epicoprosterol, and in group
      AS72.5 it decreased the degradation of cholic acid. Thus, this autoclaved
      amylomaize starch, which could be used in human nutrition, prevents
      cholelithiasis and lowers cholesterolemia.

PMID- 8536511
TI  - Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A
      randomized trial with manometric function.
AB  - To circumvent the long-term effects of papillary ablation for extracting common
      bile duct stones (< 12 mm in diameter) in endoscopic sphincterotomy (EST),
      endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate
      papillary function before and after the procedures, manometry of the sphincter of
      Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of
      all stones was successful (100%) in both groups at an equal rate. Repeated
      numbers of procedures were common in both groups. However, the mean duration of
      the procedure was high in EPD compared to EST (63 min vs 42 min, P < NS).
      Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and
      choledochoscopy were included in EPD, while EST required a basket catheter and
      ML. There was no significant difference on manometry before and after the
      procedures (P = NS), although papillary function was found to have decreased
      after the EPD. In contrast, all patients in the EST group lost papillary function
      after the procedure. Thirty-day morbidity and mortality rate were absent in both
      groups. Immediate and 2.5-year follow up complications were uncommon in both
      groups. As a simple method, EPD may be an effective and safe alternative to EST
      in the management of patients with bile duct stones who require maintenance of
      papillary function.

PMID- 8536512
TI  - Pancreatic enzyme therapy in childhood celiac disease. A double-blind prospective
      randomized study.
AB  - The validity of pancreatic enzyme substitution therapy in the two months
      following diagnosis of celiac disease was investigated. Twenty patients (8 males,
      12 females), mean age 14.2 months (group A) received an enzyme substitution
      preparation. The control group (group B) included 20 patients (9 males, 11
      females), mean age 14.5 months, treated with placebo. Before starting treatment,
      we performed a stratification for age, weight-for-age at diagnosis, and degree of
      pancreatic insufficiency. The therapies were then administered randomly in double
      blind fashion. On diagnosis and 30 and 60 days after commencement of a gluten
      free diet with identical calorie intake in both groups, a series of
      anthropometric variables were determined. After 30 days weight increase in group
      A patients was significantly higher (in grams) than in group B: 1131 +/- 461 vs
      732 +/- 399 (P < 0.006). Weight-for-age increase also was greater in group A than
      in group B: 9.2 +/- 5.1% vs 5.0 +/- 4.0% (P < 0.002). The increase in height Z
      score, weight-for-height, arm circumference, and subscapular and tricipital fold
      measurements were greater in group A patients than those in group B, but the
      difference was not significant. After 60 days of therapy none of the parameters
      considered were significantly different in the two groups. We concluded that
      pancreatic enzyme therapy is certainly useful in the first 30 days after
      diagnosis of celiac disease.

PMID- 8536513
TI  - Ultrastructural study on hyperplastic epithelium of rat common bile duct after
      choledochoenterostomy.
AB  - Hyperplasia of the choledochal epithelium occurs in rats after
      choledochoenterostomy. It is tubular or papillary and not like small intestinal
      mucosa in rats with choledochojejunostomy. It is, however, like large intestinal
      mucosa in rats with choledochocolonostomy. We investigated the ultrastructure of
      the hyperplastic epithelium in the two experimental groups of rats in this study.
      The main constituent cells of the hyperplasia of both the groups were like the
      principal cells of the control, but differed in that they had long microvilli and
      contained an aggregation of mucus droplets and an increased number of lysosomes.
      These findings were not seen in the control. The microvilli were sparse in the
      choledochojejunostomy group, but were dense in the choledochocolonostomy group.
      These findings suggest that the main function of the epithelium may be
      cytoprotection in the choledochojejunostomy group and both resorption and
      cytoprotection in the choledochocolonostomy group.

PMID- 8536514
TI  - Gallbladder stone recurrence after medical treatment. Do gallstones recur true to
      type?
AB  - Medical treatments that dissolve or remove gallbladder stones but leave the
      gallbladder in situ have the disadvantage of gallstone recurrence. Little is
      known about the composition of recurrent stones or whether they recur true to
      type. In 21 patients with recurrent stones detected 5-74 months (mean +/- SEM, 26
      +/- 4 months) after being rendered stone-free with dissolution therapy (N = 15)
      or percutaneous cholecystolithotomy (N = 6), we compared pretreatment and
      postrecurrence gallstone number, maximum gallstone attenuation scores measured by
      computed tomography (CT) and, in 13, the dissolvability of the recurrent stones
      with oral bile acids +/- extracorporeal shock-wave lithotripsy. Before treatment,
      five patients had solitary and 16 had multiple stones but on recurrence, the
      gallstones differed in number from the primary stones in 10 of the 21 patients.
      As a result of patient selection, before dissolution, the primary stones were all
      radiolucent with maximum CT scores of < 100 Hounsfield units (HU) (mean 45, range
      10-84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15
      patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all
      six patients treated by percutaneous cholecystolithotomy had radio-opaque stones,
      with a mean CT score of 459 (range 100-969) HU. However, on recurrence, only one
      had calcified stones (HU 140); the remaining five had CT-lucent stones (16-98 HU,
      P < 0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent
      stones were treated with oral bile acids +/- lithotripsy, 12 (92%) showed
      evidence of gallstone dissolution. We conclude that gallbladder stones do not
      recur true to type in up to two thirds of patients. However, irrespective of
      original gallstone composition, recurrent stones are usually radio- and CT
      lucent, presumed cholesterol-rich, and therefore potentially dissolvable with
      oral bile acids.

PMID- 8536516
TI  - Increasing gallstone prevalence and cholecystectomy rate in a large Romanian
      town. A necropsy study.
AB  - To study whether the increasing prevalence of gallstone disease noted in a 100
      year interval in a large Romanian town has continued in recent years, we analyzed
      all necropsies (5234) performed during 10 years (1983-1992) in Cluj-Napoca.
      Gallstone disease (GD) was defined as the presence of stones or the absence of
      the gallbladder due to cholecystectomy. The results obtained were compared to
      those of the previous 10-year period (1973-1982). We found a significant increase
      of GD both in men (6.9% to 9.8%) (P < 0.001) and women (17.1% to 21.7%) (P <
      0.001). The ratio of women to men with GD decreased as compared to the first time
      period (1.4/1 vs 1.8/1). The actual age-standardized prevalence of GD was higher
      than that calculated for the first time period: 7.6% in men (5.0% in 1973-1982)
      and 16.9% in women (8.4% in 1973-1982) (P < 0.001). The necropsy cholecystectomy
      rate rose markedly; 42.1% of the GD men and 43.0% of the GD women had undergone
      operation during their life. The present study indicates a higher prevalence of
      GD in the Romanian town than previously found. The actual prevalence is
      comparable with that of other central European countries, but it is less than
      that found in England, Scotland, or Sweden.

PMID- 8536515
TI  - Alterations of exocrine pancreas in end-stage renal disease. Do they reflect a
      clinically relevant uremic pancreopathy?
AB  - Serum pancreatic enzyme behavior, exocrine function, and morphology of the
      pancreas were studied in 28 patients with end-stage renal disease undergoing
      regular hemodialysis, in order to better delineate and assess the clinical
      relevance of the pancreatic alterations that occur in these patients. Twenty
      eight healthy subjects served as controls. Initial studies included serum
      amylase, isoamylase, and lipase assays; fecal chymotrypsin measurement; and
      abdominal ultrasonography. The amylase, lipase, and chymotrypsin determinations,
      as well as ultrasound examination, were repeated four years later. None of the
      patients had clinical evidence of pancreatic disease at entry into the study, but
      one had had previous attacks of pancreatitis and another developed mild acute
      pancreatitis one month after entry. Initial mean serum enzyme levels were
      significantly higher in patients than in controls (amylase, pancreatic
      isoamylase, and lipase, P < 0.001; salivary isoamylase P < 0.05). Serum amylase
      was raised in 16/28 patients; pancreatic isoamylase in 15/28, and lipase in 7/28;
      these elevations were generally mild. Mean fecal chymotrypsin was significantly
      lower (P < 0.001) in patients than in controls: abnormally low values were found
      in 9/28 patients. Amylase, lipase and chymotrypsin measurements repeated after
      four years showed no significant difference with respect to the first study.
      Ultrasonographic changes were rare and mild: one patient had a small cyst in the
      pancreas head, another, an increase in echogenicity of the gland not related to
      age; these findings were unchanged at repeat examination. The results demonstrate
      that the frequent elevations of serum pancreatic enzymes and the rare sonographic
      changes found in patients undergoing hemodialysis do not generally reflect a
      relevant pancreopathy. However, the finding of significantly decreased fecal
      chymotrypsin may indicate the presence of pancreatic dysfunction in end-stage
      renal disease.

PMID- 8536517
TI  - Alpha-fetoprotein and p53 autoantibodies in patients with chronic hepatitis C.
AB  - Hepatitis C virus infection is a common cause of chronic liver disease and
      hepatocellular carcinoma. Recently, mutations in the p53 tumor suppressor gene
      with generation of circulating autoantibodies to p53 protein have been detected
      in a significant proportion of patients with different malignancies. Using ELISA
      methods we assessed alpha-fetoprotein and anti-p53 as serological screening
      parameters for hepatocellular carcinoma in 147 consecutive patients with chronic
      hepatitis C. Liver cirrhosis was histologically diagnosed in 58 patients (39.5%)
      and a hepatocellular carcinoma confirmed in seven patients (4.8%). Serum alpha
      fetoprotein was raised above 20 ng/ml in 26/147 patients and above 100 ng/ml in
      5/147 patients. In 6/7 patients with hepatocellular carcinoma, alpha-fetoprotein
      was raised above 20 ng/ml, but only in 3/7 cases above 100 ng/ml, resulting in a
      sensitivity and specificity of 85.7% and 85.7% (alpha-fetoprotein > 20 ng/ml) and
      42.9% and 98.6% (alpha-fetoprotein > 100 ng/ml) for the detection of
      hepatocellular carcinoma, respectively. Autoantibodies to p53 were detected in
      3/7 patients with hepatocellular carcinoma, but in 0/140 patients without
      malignancy (sensitivity 42.9%, specificity 100%). Screening for hepatocellular
      carcinoma was improved by combining alpha-fetoprotein measurement (level > 100
      ng/ml) with detection for anti-p53 (sensitivity 71.4%, specificity 98.6%). In
      conclusion, the presence of anti-p53 was highly specific for malignancy and
      independent of alpha-fetoprotein status. Further studies including a larger
      number of patients with hepatitis C virus-related hepatocellular carcinoma are
      required to investigate whether serological testing for anti-p53 in combination
      with alpha-fetoprotein might improve the detection of hepatocellular carcinoma in
      high-risk patients with liver cirrhosis.

PMID- 8536518
TI  - Significance of hepatic expression of hepatitis C viral antigens in chronic
      hepatitis C.
AB  - To determine the significance of hepatic expression of hepatitis C viral (HCV)
      antigens, HCV core and NS4 antigens were detected by immunohistochemistry in 46
      patients with chronic HCV infection. Serum HCV RNA was quantitated by branched
      DNA assay in 41 and HCV genotype determined in 30 patients. HCV core and NS4
      antigens were detected exclusively in the cytoplasm of hepatocytes in 83% and 61%
      of patients, respectively. There was no correlation between the expression of HCV
      antigens and clinical, biochemical, histological parameters and HCV genotype.
      Hepatic expression of HCV antigens was positively associated with serum HCV-RNA
      levels (P < 0.02). At the end of interferon-alpha (IFN) therapy, expression of
      HCV antigens remained either unchanged or decreased in 11/12 patients studied
      (undetectable in all four patients who had complete and sustained response). We
      conclude that hepatic expression of HCV core and NS4 antigens parallels serum HCV
      RNA levels and IFN therapy reduces hepatic expression of these viral antigens.

PMID- 8536519
TI  - Chronic active hepatitis and liver cirrhosis in association with combined
      tamoxifen/tegafur adjuvant therapy.
AB  - Two female breast cancer patients who received combined tamoxifen and tegafur as
      postsurgical adjuvant therapy developed severe hepatotoxicity after being treated
      for three and eight months, respectively. Shortly after the cessation of the
      treatment, routine liver tests showed gradual recovery, but liver biopsies
      revealed chronic active hepatitis in one patient and liver cirrhosis in the
      other. Four and five years, respectively, after the cessation of the treatment,
      the results of liver tests were normal and distinct histological improvement was
      observed in both patients. Because these patients had no viral and
      immunoserological markers nor any history of alcohol abuse, this study suggested
      that the tamoxifen and tegafur regimen induced reversible chronic active liver
      disease.

PMID- 8536520
TI  - Effects of smoking on interdigestive gastrointestinal motility.
AB  - The effect of smoking on interdigestive gastrointestinal motility is little
      studied but may play a role in gastrointestinal morbidity. We studied
      gastroduodenal motility in 10 volunteers (five smokers and five nonsmokers) using
      a water-perfused pressure catheter. A pH probe was placed in the duodenal bulb.
      Baseline motility was recorded until phase III of the migrating-motor complex had
      occurred in the stomach three times in order to record two complete cycles of MMC
      activity. Subjects then began smoking until phase III activity occurred again
      (mean duration of smoking 117 min). During the control period, all subjects had
      normal MMC cycles and there were no differences between smokers and nonsmokers.
      While smoking, no gastric phase III was observed in any subject and gastric
      motility was markedly reduced. In seven of 10 subjects, smoking did not prevent
      the occurrence of normal duodenal phase III activity. Three subjects had no
      duodenal phase III activity during smoking. The duodenal pH profile did not
      change during smoking and motilin levels continued to fluctuate in conjunction
      with phase III activity. In conclusion, smoking abolished phase III activity in
      the stomach without affecting the plasma motilin cyclic fluctuations or duodenal
      bulb pH. In contrast, smoking has little effect on duodenal motility.

PMID- 8536521
TI  - Inhibitory effects of cholecystokinin on postprandial gastric myoelectrical
      activity.
AB  - While a number of studies have investigated the effects of cholecystokinin (CCK)
      on gastrointestinal motility, little is known on the effects of CCK on gastric
      myoelectrical activity, which regulates gastric motility. The aim of this study
      was to investigate the effects of intravenous infusion of CCK-8 on gastric
      myoelectrical activity in normal humans. Gastric myoelectrical activity was
      measured in 10 healthy subjects with a noninvasive electrogastrographic technique
      by placing abdominal electrodes on the epigastric area. Two study sessions were
      performed in each subject on two separate days with double-blinded infusion of
      either saline or CCK (24 pmol/kg/hr). The procedure for each session was as
      follows: (A) 30-min baseline fasting electrogastrogram (EGG); (B) start infusion,
      another 30-min EGG; (C) give meal, 60-min EGG; and (D) stop infusion, another 60
      min EGG. The dominant frequency and peak power (amplitude) of the EGG, and the
      percentage of normal 2-4 cycles/min slow waves during each recording session were
      computed and compared between placebo and CCK. It was found that normal 3 cpm
      slow waves were recorded in all EGGs. Infusion of CCK had no effect on the
      frequency of the gastric slow wave and did not induce gastric dysrhythmias. It
      was also found that intravenous infusion of CCK significantly decreased the EGG
      peak power (amplitude) during the first hour after the meal (the infusion was
      given during this period) in comparison with placebo (P < 0.05). This inhibitory
      effect on EGG peak power was sustained but not significant during the second
      postprandial hour (the infusion was not given during this period). It was
      concluded that intravenous infusion of CCK at a physiological concentration
      significantly decreased the postprandial EGG amplitude in normal humans,
      suggesting an inhibitory effect on postprandial gastric motility, but did not
      change the frequency and regularity of the gastric slow wave.

PMID- 8536522
TI  - Adrenoceptor-mediated modulation of Evans blue dye permeation of rat small
      intestine.
AB  - In the present study, we addressed the problem whether sympathoadrenal mechanisms
      could influence the paracellular permeation of macromolecules from the lumen to
      the lamina propria of the small intestine. Experiments were conducted with rats
      that were anesthetized with ether for 10-20 min, during which time laparotomy was
      performed and six consecutive loops (each of 5 cm length) of the jejunum were
      prepared. A 3% solution of the azo dye, Evans blue (EB; MW 960.83) in phosphate
      buffered saline, was instilled into each loop at a volume of 0.3 ml, this
      compound serving as a marker for tight junctional permeability. Thereafter, the
      abdomen was closed and the rats were allowed to wake up, but were killed after 60
      min. The loops were dissected, opened, and rinsed with acetylcysteine in order to
      remove the adherent mucus layer. Each loop was weighed and incubated with
      formamide for 24 hr to elute the amount of EB absorbed, which was quantitated
      spectrophotometrically. In the control situation, the uptake was homogenous along
      the loops. beta-Adrenoceptor-blocking, or -stimulating agents could influence the
      uptake considerably. The data obtained could indicate that noradrenergic nerves,
      via an activation of beta 2-adrenoceptors, may cause an increase of tight
      junction permeability for macromolecules, but circulatory mechanisms also must be
      taken into account in order to explain the observed effects.

PMID- 8536523
TI  - Detection of anti-cord factor antibodies in intestinal tuberculosis for its
      differential diagnosis from Crohn's disease and ulcerative colitis.
AB  - We have developed a diagnostic method for pulmonary tuberculosis by detecting
      antibody to cord factor using enzyme-linked immunosorbent assay (ELISA). This
      study was to evaluate the usefulness of our method for a diagnosis of intestinal
      tuberculosis, and especially its ability to differentiate this disease from other
      inflammatory bowel diseases. Antibodies of the immunoglobulin G class against
      cord factor (trehalose-6,6'-dimycolate) from 27 patients with intestinal
      tuberculosis, 16 patients with Crohn's disease (CD), and 27 patients with
      ulcerative colitis (UC) were tested by ELISA with cord factor purified from
      Mycobacterium tuberculosis H37Rv as the antigen. Twenty-three of the 27 patients
      with intestinal tuberculosis (85%) showed elevated values distinct from healthy
      controls. None of the patients with CD showed an elevation of antibody titers. Of
      the 27 patients with UC, 26 (96%) did not show any anti-cord factor antibody
      elevation. We conclude that this method is simple and results are reproducible.
      The results of our study justify undertaking the detection of anti-cord factor
      antibodies to diagnose intestinal tuberculosis.

PMID- 8536524
TI  - Intraluminal excretion of PAF, lysoPAF, and acetylhydrolase in patients with
      ulcerative colitis.
AB  - PAF-acether (PAF) is a phospholipid synthesized by numerous inflammatory cells.
      PAF can produce several pathological changes in various organs, especially in the
      colon. In animals PAF causes colonic ulceration and inflammation, which are
      similar to the anatomic lesions seen in human ulcerative colitis. The aim of this
      study was to measure in vivo colonic production of PAF in active ulcerative
      colitis using a modified colonic perfusion method. Ten patients with active
      ulcerative colitis and six control patients were investigated. A colonic segment
      was continuously perfused with a buffer and the liquid was recovered 20 cm
      distally, after a 45-min period of equilibration, at 20-min intervals. PAF,
      lysoPAF, and acetylhydrolase were measured in the colonic samples. PAF and
      lysoPAF outputs were significantly higher in patients with active ulcerative
      colitis compared to controls patients. There was a significant correlation
      between colonic PAF output and, respectively, macroscopic mucosal lesions and
      myeloperoxidase colonic output. We thus conclude: (1) the colonic perfusion
      method allows in vivo study of the metabolism of PAF during ulcerative colitis
      and could also be used to study the efficiency of PAF antagonists in UC; and (2)
      colonic production of PAF is increased during ulcerative colitis and correlated
      to local injury and inflammation. Whether or not PAF plays a role in the
      pathogenesis of ulcerative colitis remains open for further investigations.

PMID- 8536525
TI  - Bacterial enzymes used for colon-specific drug delivery are decreased in active
      Crohn's disease.
AB  - Enzymes produced by colonic microflora have been proposed for triggering local
      delivery of antiinflammatory azo-bond drugs and prodrugs to the colon. This
      approach could be advantageous in steroid treatment of inflammatory bowel
      diseases, thus sparing steroids' side effects. We recently demonstrated that the
      metabolic activity of digestive flora, assessed on the activity of fecal
      glycosidases, was decreased in patients with active Crohn's disease. In the
      present study, the azoreductase activity in feces of 14 patients with active
      Crohn's disease was decreased (11.39 +/- 7.93 mU/g F) as compared with 12 healthy
      subjects (51.13 +/- 21.39 mU/g F). beta-D-Glucosidase and beta-D-glucuronidase
      activities in fecal homogenates incubated under anaerobic conditions were also
      decreased in patients. These data bring into question the therapeutic usefulness
      for those patients of azo-bond drugs and glycoside prodrugs. They could explain
      the therapeutic failure of some of those drugs in active ileocolic and colic
      Crohn's disease.

PMID- 8536526
TI  - Irritable bowel syndrome defined by factor analysis. Gender and race comparisons.
AB  - To examine the applicability across subgroups of the Manning criteria commonly
      used to diagnose the irritable bowel syndrome, a 22-item symptom questionnaire
      was administered to male and female African-American and Caucasian adults (N =
      1344). Principal components factor analysis with varimax rotation was used to
      identify symptom clusters. Consistent with the findings of a previous factor
      analytic study, three of the six Manning symptoms (loose stools and more frequent
      bowel movement with onset of pain, pain relieved by defecation) formed a cluster
      corresponding to the irritable bowel syndrome in all subgroups. It is concluded
      that: (1) The three core Manning symptoms have equal applicability to both
      genders and to African-Americans as well as to Caucasians. They useful symptom
      criteria for the diagnosis of IBS when used in conjunction with medical
      evaluation. (2) Three of the six Manning symptoms rarely correlate with the
      others; if confirmed in patient samples, this would indicate that these three
      symptoms are not useful for making a diagnosis of the irritable bowel syndrome.

PMID- 8536527
TI  - Wandering spleen with torsion in a geriatric patient. Report of an unusual case
      with a brief review of the clinical picture and management.
AB  - Wandering spleen is a rare condition that is extremely uncommon in the elderly. A
      case of wandering spleen with torsion in a 73-year-old female is described in
      detail. Our patient's presentation is unusual because in 1972, during a total
      hysterectomy, she had no evidence of a wandering spleen. Preoperative technetium
      99 radionuclide liver-spleen studies were utilized to minimize the potential for
      vascular difficulties. Splenectomy was the treatment of choice for this condition
      and was performed to avoid splenic infarction. A review of the literature and
      etiologic considerations are discussed.

PMID- 8536528
TI  - Colon transit scintigraphy using oral indium-111-labeled DTPA. Can scan pattern
      predict final diagnosis?
AB  - Colon transit scintigraphy (CTS) was performed in 100 consecutive patients with
      idiopathic constipation using oral indium-111-labeled DTPA. Criteria were defined
      to allow classification of studies as normal, slow transit constipation (STC), or
      obstructed defecation (OD). Results were compared with final clinical diagnosis
      in 100 and findings of defecating proctography in 70. Of those with a
      scintigraphic diagnosis of STC, this was also the final diagnosis in 75% (33 of
      44), and the scintigraphic diagnosis of OD was confirmed in 61% (17 of 28). Of 28
      normal or equivocal scans, the final diagnosis was STC in only two (4%) but OD in
      10 (21%). Fifty-four percent of patients with STC and 71% with OD had abnormal
      proctograms. The correlation between CTS and proctography was mediocre, occurring
      in 54% of patients. CTS has a valuable role in the diagnostic work-up of patients
      with idiopathic constipation.

PMID- 8536529
TI  - Prevalence of Helicobacter pylori infection in infants and family contacts in a
      poor Bangladesh community.
AB  - Although H. pylori is well established as an etiological agent of type B
      gastritis and a predisposing factor for peptic ulcer, knowledge about its
      transmission is unclear. In this study we examined the prevalence of H. pylori
      infection in the family members of index infants infected with this organism as
      indicated by positive [13C]-urea breath test (UBT). We performed UBT among family
      members of 15 predominantly breastfed infants, eight with and seven without H.
      pylori infection. Infection rates were 82% and 91% in family contacts of the
      infected and noninfected infants respectively, the average infection rate being
      85%, which is rated to be high. There was no difference in infection rates among
      the parents of the infected and noninfected infants. Fifty percent and 70%
      families belonging to infected and noninfected infants, respectively, were found
      to have all members infected with H. pylori. No evidence of sex predilection of
      infection was found. We conclude that in communities with high prevalence of H.
      pylori infection, there is almost an equal infection rate among the family
      contacts of infected and noninfected infants, suggesting that environmental
      factors may be more important than intrafamilial transmission.

PMID- 8536530
TI  - Perception of gastric distension. Influence of mode of distension on perception
      thresholds and gastric compliance.
AB  - Gastric distension has been used to evaluate gastric sensory function in humans,
      but the methodology is poorly validated and studies in vivo comparing different
      distension protocols are lacking. We aimed to compare the influence of the mode
      of gastric distension on sensation and gastric compliance utilizing a barostat
      device. In seven healthy volunteers, we positioned a barostat bag in the proximal
      stomach and tested in random order (in triplicate) four different distension
      protocols: (1) standard ramp distension with 4 mm Hg pressure step increments of
      20 sec duration; (2) slow ramp distension with 2 mm Hg pressure increments of 40
      sec duration; (3) random distension using a pressure ramp consisting of 2 mm Hg
      increments of 40 sec duration with randomly interposed pressure steps 50% below
      the preceding pressure step; and (4) rapid random distension with 4 mm Hg
      pressure increments of 10 sec duration with randomly interposed pressure steps
      50% below the preceding pressure step. The distension procedures yielded mean
      airflow rates during the different distension protocols between 2.4 ml/sec for
      standard ramp and 18.4 ml/sec for rapid random distension. First perception and
      maximal tolerable pressure were 10.9 +/- 1.1 mm Hg and 19.6 +/- 1.5 mm Hg,
      respectively. First perception and maximal tolerable pressures were significantly
      correlated (r = 0.93, P < 0.005). The gastric pressure at occurrence of
      perception and the maximal tolerated pressure were not significantly different
      for the different distension protocols but gastric compliance was significantly
      reduced during rapid ramp distension (P < 0.01 vs slow ramp and P < 0.05 vs
      random distension) but not during standard ramp distension. We conclude that
      gastric sensory pressure thresholds as assessed by isobaric distension are not
      influenced by the mode of distension. The high correlation of pressure thresholds
      at first perception and maximal tolerated distension suggest a single population
      of gastric mechanoreceptors that mediate first sensation at low intensity
      stimulation and pain at intense stimulation.

PMID- 8536531
TI  - Inadequate response to H2-receptor antagonists. Absence of parietal cell cAMP
      stimulating autoantibodies.
AB  - In peptic ulcer patients with adequate (AR; N = 16) and inadequate response (IR;
      N = 20) to H2-receptor antagonists, the presence of parietal cell cAMP
      stimulating autoantibodies was studied. Serum Ig fractions from these patients
      and 10 control subjects were examined to test whether they could stimulate cAMP
      production in a gastric cell line model. The human cell line HGT-1 was found to
      be a sensitive in vitro model for the cAMP stimulation assay as histamine (10
      microM) increased by 11-fold the production of cAMP. Neither IgG (4 mg/ml) nor
      IgG-free Ig fractions (1 mg/ml) isolated from the blood of AR or IR affected cAMP
      production in the HGT-1 cells. The results obtained with the cAMP stimulation
      assay were confirmed by indirect immunofluorescence measurements based on frozen
      sections of rat stomach and kidney. No specific staining of rat parietal cells
      could be observed with patient sera. In addition, human gastric biopsies of the
      oxyntic mucosa from the same patients were studied for immunoreactive cell
      populations to assess organ-specific autoimmune processes. Biopsy specimens from
      AR and IR showed increased lymphocytic infiltrates, usually associated with
      gastritis. However, no significant differences in location of various cell
      populations between AR and IR could be observed. Our findings do not support a
      recent hypothesis that poor response to treatment with H2-receptor antagonists is
      due to the presence of autoantibodies.

PMID- 8536532
TI  - NSAID-induced delay in gastric ulcer healing is not associated with decreased
      epithelial cell proliferation in rats.
AB  - Nonsteriodal antiinflammatory drugs initiate gastric ulceration and delay gastric
      ulcer healing. This study aimed to investigate the role of epithelial cell
      proliferation in delayed ulcer healing and to identify the most reproducible
      technique for measuring cell proliferation. Rats with acetic acid-induced gastric
      ulcers were treated for two weeks with indomethacin (1 mg/kg), aspirin (200
      mg/kg), or vehicle control. Ulcers were assessed by macroscopic measurement of
      ulcer area, quantitative histological measurement of mucosal regeneration, and 5
      bromo-2'-deoxyuridine immunohistochemistry to assess epithelial cell
      proliferation. Indomethacin and aspirin significantly delayed ulcer healing and
      inhibited mucosal regeneration. Three techniques for assessing cell proliferation
      were compared, and a scoring system, designed to take into account the entire
      tissue, was shown to be the most reproducible technique. Indomethacin
      significantly enhanced cell proliferation in the fundic area of ulcer and aspirin
      had no effect on cell proliferation. We conclude that aspirin and indomethacin
      delay ulcer healing by an inhibition of mucosal regeneration, but they do not
      inhibit epithelial cell proliferation.

PMID- 8536533
TI  - Neutropenia does not prevent etodolac- or indomethacin-induced gastrointestinal
      damage in the rat.
AB  - Neutrophils have been implicated in the acute formation of gastric mucosal
      erosions induced by nonsteroidal antiinflammatory drugs. The aims of the present
      study were to determine, in rats, the role of neutrophils in the pathogenesis of
      etodolac- and indomethacin-induced gastrointestinal ulceration and blood loss.
      Both drugs caused gastrointestinal ulceration, which was associated with
      increased blood loss, a rise in plasma haptoglobin concentration, and a rise in
      the number of circulating neutrophils. A marked infiltration of neutrophils
      occurred only in ileal tissue. Pretreatment with a selective antineutrophil serum
      induced a significant neutropenia, which failed to inhibit either etodolac- or
      indomethacin-induced gastrointestinal ulceration and blood loss. A further study
      demonstrated that the antineutrophil serum did not prevent gastric erosions
      induced by indomethacin, but it inhibited carrageenan paw edema, which is
      dependent, in part, on neutrophil infiltration and activation. It is concluded
      that neutrophils do not contribute to gastrointestinal ulceration and blood loss
      induced by nonsteroidal antiinflammatory drugs. Furthermore, in contrast with
      previous studies, our results provide no evidence that neutrophils contribute to
      indomethacin-induced acute gastric erosion formation.

PMID- 8536534
TI  - Relationships between metal ions and oxygen free radicals in ethanol-induced
      damage to cultured rat gastric mucosal cells.
AB  - The current study investigated whether metal ions were cytoprotective against
      ethanol-induced injury to cultured rat gastric mucosal cells in vitro. Secondly,
      the relationships between oxygen free radicals and cytoprotection by metal ions
      were examined. Cultured cells exposed to ethanol produced superoxide anion, as
      assessed by reduction of cytochrome c, in a time-related fashion, and the
      production of superoxide anion increased dose-dependently as the concentration of
      ethanol increased. Cellular damage increased proportionately to the production of
      superoxide anion. ZnCl2, AlCl3, CoCl2, CuCl2, and CdCl2 significantly diminished
      ethanol-induced injury dose-dependently. All of the agents studied decreased the
      reduction of cytochrome c in ethanol-induced damage dose-dependently. These
      results led to the conclusions that: (1) cultured rat gastric mucosal cells
      exposed to ethanol generate oxygen free radicals; (2) the production of oxygen
      free radicals is closely linked with ethanol-induced damage to the cells; and (3)
      metal ions decrease ethanol-induced gastric mucosal cell damage in vitro. Metal
      ions protect cultured rat gastric mucosal cells from ethanol-induced damage in
      which oxygen free radicals participate.

PMID- 8536535
TI  - Gastric metabolism of ethanol in Syrian golden hamster.
AB  - First-pass metabolism (FPM) of orally ingested alcohol has been attributed to
      gastric alcohol dehydrogenase (ADH) activity in both humans and rats. To
      determine whether gastric alcohol dehydrogenase is essential for alcohol FPM, we
      sought a species lacking this enzyme. We found that Syrian golden hamsters have
      negligible gastric ADH yet alcohol FPM (265 +/- 25 mg ethanol/kg) was comparable
      to that of rats (251 +/- 31 mg/kg). To determine whether hamster gastric mucosal
      cells metabolize sufficient alcohol to account for this FPM, primary cultures
      were established, and these cells metabolized 1.99 +/- 0.84 mumol ethanol/10(6)
      cells/hr, an amount sufficient to account for the bulk of alcohol FPM. In
      contrast to alcohol dehydrogenase, catalase activity in hamster gastric mucosa
      (870 +/- 93 units/g tissue) was eightfold higher than in rat gastric mucosa (111
      +/- 9 units/g tissue; P < 0.0001). FPM in hamsters treated with 3-aminotriazole
      was reduced from 242 +/- 24 to 130 +/- 22 mg/kg (P < 0.05) but was not reduced in
      rats. The results imply that catalase participates in gastric alcohol metabolism
      of hamsters.

PMID- 8536536
TI  - Chronic treatment with epidermal growth factor causes esophageal epithelial
      hyperplasia in pigs and rats.
AB  - Epidermal growth factor (EGF) is an important factor for maintaining the
      esophageal functional integrity. Goettingen minipigs were treated with either
      placebo or subcutaneous EGF (30 micrograms/kg/day) for four weeks. Wistar rats
      were treated with either placebo or subcutaneous EGF (150 micrograms/kg/day) for
      four weeks. At sacrifice, esophageal samples were obtained for histology,
      immunochemistry, and lectin characterization. In pigs, the thickness of the
      esophageal epithelium was almost doubled in the EGF-treated animals.
      Characterization with lectins revealed a normal pattern of differentiation.
      Subcutaneously administered EGF was visualized on cells located basally in the
      esophageal epithelium. In rats, EGF-treatment increased the esophageal volume of
      the epithelium, the lamina propria of the mucosa, and the submucosa. In
      conclusion, systemic EGF challenge induces growth of the esophageal epithelium
      with an unaltered pattern of differentiation. This supports previous studies
      demonstrating a beneficial effects of systemic EGF-treatment on sclerotherapy
      induced esophageal damage.

PMID- 8536537
TI  - Effect of hiatal hernia on esophageal manometry and pH-metry in gastroesophageal
      reflux disease.
AB  - An increased frequency of reflux events and a prolonged acid clearance have been
      shown in gastroesophageal reflux (GER) patients with a hiatal hernia as compared
      to those without. The objective of the present study was to further investigate
      esophageal motility and patterns of reflux in GER patients, in relation to the
      presence or absence of hiatal hernia. Esophageal manometry and ambulatory 24-hr
      esophageal pH-metry were used in 42 patients with GER and 18 controls. Eighteen
      of the patients were considered to have a nonreducing hiatal hernia on endoscopy.
      Hiatal hernia patients showed a higher extent of reflux (total composite score, P
      = 0.016; total reflux time, P = 0.008, reflux time in supine position, P = 0.024;
      reflux time in upright position, P = 0.008), a lower frequency of reflux events
      (P = 0.005), a more severe esophagitis on endoscopy (P < 0.01) and a lower
      amplitude of peristalsis at 5 cm proximal to LES (P = 0.0009) as compared to
      patients without hiatal hernia. The amplitude of peristalsis at the distal
      esophagus was inversely related to the extent of reflux (P = 0.024). Acid
      clearance was also significantly prolonged in the hernia subgroup (P = 0.011).
      Although LES resting pressure did not differ significantly between the two
      subgroups of patients, it was inversely related to the extent of reflux in the
      patients with hiatal hernia (P = 0.0005). It is concluded, that GER patients with
      hiatal hernia present with an increased amount of reflux and more severe
      esophagitis, which results in more severely impaired esophageal peristalsis as
      compared to patients without hernia. Prolonged acid clearance and impaired
      esophageal emptying observed in patients with hiatal hernia could be the result
      of both the presence of the hernia itself and the reduced peristaltic activity of
      the esophagus.

PMID- 8536538
TI  - Metronidazole affects Helicobacter pylori related nonulcer dyspepsia and symptoms
      from carbohydrate malabsorption.

PMID- 8536539
TI  - Nervous system abnormalities in diabetes. Introduction.

PMID- 8536540
TI  - The role of oxidative stress in neuropathy and other diabetic complications.

PMID- 8536541
TI  - Pathology and pathogenetic mechanisms of diabetic neuropathy.

PMID- 8536542
TI  - Diabetic autonomic neuropathy.

PMID- 8536543
TI  - Electrophysiological alterations of the central nervous system in diabetes
      mellitus.

PMID- 8536544
TI  - Impotence in diabetes mellitus.

PMID- 8536545
TI  - The drug treatment of patients with schizophrenia.

PMID- 8536546
TI  - Patient pack prescribing and the provision of patient information leaflets.

PMID- 8536547
TI  - Mucosal vaccines for the prevention of influenza.

PMID- 8536548
TI  - Growth hormone secretagogues. Clinical experience and therapeutic potential.
AB  - In recent years, several biosynthetic hexa- and heptapeptides, as well as
      nonpeptide bezolactam derivatives, have been found to be potent growth hormone
      (GH) secretagogues. They act synergistically with GH-releasing hormone (GHRH) but
      via different receptors, and are GHRH dependent. All are active when administered
      intravenously, orally or subcutaneously. Short and long term experience in adults
      and children has proven that these drugs evoke the metabolic changes induced by
      GH and insulin-like growth factor-1 (IGF-1), including acceleration of growth
      velocity in children. With the exception of a partial downregulation phenomenon,
      no adverse effects have been reported so far. This new class hormone-like drugs
      acting GH secretagogues may have immense clinical potential.

PMID- 8536549
TI  - Current management of von Willebrand's disease.
AB  - von Willebrand's disease (vWD) is the most frequent inherited disorder and is the
      result of a deficiency and/or abnormality of von Willebrand factor (vWF). As a
      consequence, the level of factor VIII, the presence of which reflects the ability
      of vWF to stabilise it, is usually low. Bleeding time, which reflects the ability
      of vWF to promote platelet adhesion to subendothelium, is therefore prolonged.
      However, from a therapeutic point of view, it appears that the correction of
      factor VIII and bleeding time is sufficient to prevent or treat bleeding in these
      patients. There are 2 main therapeutic tools to improve or normalise these major
      determinants of the bleeding tendency in this disorder. The majority of patients,
      identified by a test infusion, can be successfully treated by giving desmopressin
      (DDAVP), a synthetic analogue of vasopressin. Desmopressin is able to induce the
      increase of autologous vWF released from endothelial cells, leading to the
      correction of factor VIII levels and of bleeding time. In the remaining cases,
      blood products, namely factor/vWF concentrates, are required to accomplish
      haemostasis. All these concentrates are able to correct factor VIII levels,
      whereas their effect on bleeding time may not be consistent. The modern virucidal
      techniques abolish the risk of transmission of blood-borne viruses (e.g.
      hepatitis viruses and HIV) and make these products safer than blood-bank
      cryoprecipitate.

PMID- 8536550
TI  - Guidelines for general practitioners administering thrombolytics.
AB  - Acute myocardial infarction (AMI) recognises no boundaries, and the patient's
      greatest need occurs at the interface between primary care and hospital system.
      Ideally, the general practitioner, if summoned, should be able to provide
      resuscitation, analgesia with opiates, and thrombolytic therapy. Thrombolytics
      should certainly be given to eligible patients by the general practitioner if an
      hour could be saved by so doing. Optimising the risk-benefit ratio for
      thrombolytic therapy given in the community is a challenge to clinical judgement.
      Experience with this potent treatment is best obtained under a degree of
      supervision, which could take the form of an audit of the prehospital management
      of suspected AMI. With prehospital administration of thrombolytic therapy at the
      first opportunity, the chances of saving a life are better than 1 in 10, while
      the excess risk of a disabling stroke is about 1 in 1000.

PMID- 8536551
TI  - Drug management of noninfective complications of cystic fibrosis.
AB  - Cystic fibrosis (CF) is the commonest lethal hereditary disease in Caucasians.
      The disease involves a gene mutation located at the long arm of chromosome 7, and
      more than 300 mutations have been identified. CF is a systemic illness affecting
      the upper respiratory tract and airways, sweat and salivary glands, pancreas,
      gastrointestinal tract, liver and male reproductive system. The course is highly
      variable depending on the specific molecular abnormalities in the mutant gene.
      The current approach to therapy now involves the use of: (i) chest physiotherapy;
      (ii) bronchodilators when there is evidence of airways hyperreactivity; (iii)
      oral and intravenous antibiotics for acute pulmonary exacerbations and
      aerosolised antibiotics for prevention; (iv) recombinant human deoxyribonuclease
      I (dornase alfa) to promote airways clearance; (v) amiloride to improve sputum
      viscosity; (vi) pancreatic enzyme replacement therapy along with nutritional
      support and supplements; (vi) vitamins; and (vii) ursodeoxycholic acid in
      selected patients. The use of antiprotease and anti-inflammatory agents has been
      shown to be useful in preventing the damage secondary to chronic lung infection.
      In patients with severely impaired lung function, lung transplantations have been
      performed with good results. Finally, it seems probable that lung disease in CF
      patients will be ameliorated or prevented in the future with early gene therapy,
      using vectors such as recombinant adenoviruses, adeno-associated virus,
      lipofection or retrovirus. However, this require extensive basic and clinical
      research.

PMID- 8536552
TI  - Propofol. An overview of its pharmacology and a review of its clinical efficacy
      in intensive care sedation.
AB  - Propofol is a phenolic derivative that is structurally unrelated to other
      sedative hypnotic agents. It has been used extensively as an anaesthetic agent,
      particularly in procedures of short duration. More recently it has been
      investigated as a sedative in the intensive care unit (ICU) where it produces
      sedation and hypnosis in a dose-dependent manner. Propofol also provides control
      of stress responses and has anticonvulsant and amnesic properties. Importantly,
      its pharmacokinetic properties are characterised by a rapid onset and short
      duration of action. Noncomparative and comparative trials have evaluated the use
      of propofol for the sedation of mechanically ventilated patients in the ICU
      (postsurgical, general medical, trauma). Overall, propofol provides satisfactory
      sedation and is associated with good haemodynamic stability. It produces results
      similar to or better than those seen with midazolam or other comparator agents
      when the quality of sedation and/or the amount of time that patients were at
      adequate levels of sedation are measured. Patients sedated with propofol also
      tend to have a faster recovery (time to spontaneous ventilation or extubation)
      than patients sedated with midazolam. Although most studies did not measure time
      to discharge from the ICU, propofol tended to be superior to midazolam in this
      respect. In a few small trials in patients with head trauma or following
      neurosurgery, propofol was associated with adequate sedation and control of
      cerebral haemodynamics. The rapid recovery of patients after stopping propofol
      makes it an attractive option in the ICU, particularly for patients requiring
      only short term sedation. In short term sedation, propofol, despite its generally
      higher acquisition costs, has the potential to reduce overall medical costs if
      patients are able to be extubated and discharged from the ICU sooner. Because of
      the potential for hyperlipidaemia and the development of tolerance to its
      sedative effects, and because of the reduced need for rapid reversal of drug
      effects in long term sedation, the usefulness of propofol in long term situations
      is less well established. While experience with propofol for the sedation of
      patients in the ICU is extensive, there are still areas requiring further
      investigation. These include studies in children, trials examining cerebral and
      haemodynamic outcomes following long term administration and in patients with
      head trauma and, importantly, pharmacoeconomic investigations to determine those
      situations where propofol is cost effective. In the meantime, propofol is a well
      established treatment native to benzodiazepines and/or other hypnotics or
      analgesics when sedation of patients in the ICU is required. In particular,
      propofol possesses unique advantages over these agents in patients requiring only
      short term sedation.

PMID- 8536554
TI  - Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy.
AB  - Lamotrigine is an antiepileptic agent which blocks voltage-dependent sodium
      channels, thereby preventing excitatory neurotransmitter release. Clinical
      evidence indicates that lamotrigine is effective against partial and secondarily
      generalised tonic-clonic seizures, as well as idiopathic (primary) generalised
      epilepsy. As monotherapy, lamotrigine 100 to 300 mg/day has similar medium term
      (30 to 48 weeks) efficacy to carbamazepine 300 to 1400 mg/day and phenytoin 300
      mg/day against partial onset seizures and idiopathic generalised tonic-clonic
      seizures in adults with newly diagnosed epilepsy, and appears to be better
      tolerated than the older agents. As adjunctive therapy, lamotrigine (50 to 500
      mg/day) has shown efficacy in short term ( < or = 6-months) placebo-controlled
      studies in adults with refractory partial epilepsy, reducing total seizure
      frequency (by < or = 60%) and producing improvement ( > or = 50% reduction in
      seizure frequency) in < or = 67% of patients. Both simple and complex partial
      seizures and secondarily generalised tonic-clonic seizures are reduced by
      lamotrigine, with generalised seizures (particularly absence seizures, atonic
      seizures and Lennox-Gastaut syndrome) tending to be more responsive than partial
      seizures. This reduction in seizure frequency is sustained on long term ( < or =
      3 years) therapy and is reportedly accompanied by an improvement in psychological
      well-being. In children with refractory multiple seizure types, lamotrigine ( <
      or = 15 mg/kg/day; 400 mg/day) has proved effective as add-on therapy, with
      approximately equal to 40% of patients showing > or = 50% reductions in seizure
      frequency and approximately equal to 10 % achieving abolition of seizures after 3
      months' treatment. Generalised seizures, including atypical and typical absence
      seizures, atonic and tonic seizures and Lennox-Gastaut syndrome are most
      responsive. The most common adverse events associated with lamotrigine are
      primarily neurological, gastrointestinal and dermatological. Maculopapular or
      erythematous skin rash, occasionally severe, occurs in approximately equal to 10%
      of patients and is the most common cause of treatment withdrawal. The risk of
      rash can, however, be minimised through adoption of a low, slow dosage titration
      schedule on initiating therapy. As monotherapy, lamotrigine produces less
      drowsiness than carbamazepine or phenytoin, and less asthenia and ataxia than
      phenytoin. Clinical experience would therefore suggest that lamotrigine is a
      particularly effective and generally well tolerated broad-spectrum agent for
      adjunctive treatment of both partial epilepsy and idiopathic generalised epilepsy
      in adults and children. Initial indications point to the drug filling an
      increasingly important future role in the monotherapy of newly diagnosed
      epilepsy.

PMID- 8536553
TI  - Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and
      therapeutic use in major superficial and systemic mycoses in immunocompromised
      patients.
AB  - Fluconazole is a triazole antifungal agent which is now an established part of
      therapy in patients with immune deficiencies. It is effective against
      oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily
      either as treatment or secondary prophylaxis in patients with AIDS or as
      treatment or primary prophylaxis in neutropenia associated with cancer therapy.
      Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal
      meningitis and AIDS. However, in this infection its efficacy as treatment
      relative to that of amphotericin B is equivocal, and its major role is as the
      drug of choice for maintenance therapy following amphotericin B induction. In
      this regard, fluconazole has been proven superior to amphotericin B and to
      itraconazole 200 mg/day. Comparisons with other drugs used for the treatment of
      mucosal candidiasis in patients with AIDS show fluconazole to be superior to
      nystatin, similar to itraconazole and at least as effective as clotrimazole and
      ketoconazole; it was more so than the latter azole in 1 study. In patients
      undergoing chemotherapy or bone marrow transplantation, fluconazole as primary
      prophylaxis has produced greater clinical benefit than a clotrimazole regimen.
      The incidence of adverse events appears to be somewhat higher in patients with
      AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is
      similar. The most frequent events are gastrointestinal complaints, headache and
      skin rash: rare exfoliative skin reactions and isolated instances of clinically
      overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be
      clarified include: the use of fluconazole in children with AIDS, in whom results
      have been promising; its efficacy against other fungal infections encountered in
      immunocompromised patients; whether the drug influences mortality, as has been
      suggested by one placebo-controlled trial in patients undergoing bone marrow
      transplant; and the appropriateness of its potential for use as primary
      prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows
      efficacy but there is concern over increasing risk of development of secondary
      resistance. Notwithstanding these undefined aspects of its clinical profile,
      fluconazole is now confirmed as an important antifungal drug in the management of
      fungal infections in patients with immune deficiencies. In patients with AIDS it
      is the present drug of choice as maintenance therapy against cryptococcal
      meningitis and is a preferred agent for secondary prophylaxis against candidal
      infections; it is also a favoured agent for primary prophylaxis in patients at
      risk because of neutropenia associated with chemotherapy or bone marrow
      transplantation .

PMID- 8536557
TI  - Allergy: a commonly neglected etiology of serous otitis media.

PMID- 8536555
TI  - Artesunate. A review of its pharmacology and therapeutic efficacy in the
      treatment of malaria.
AB  - Artesunate is an antimalarial agent, available in oral, rectal and parenteral
      formulations, that provides a rapid clinical effect in patients with Plasmodium
      falciparum malaria. The rapidity of effect, availability of an intravenous and
      intramuscular formulation and convenient dosage regimen make artesunate an ideal
      candidate for the treatment of severe malaria, including cerebral disease. While
      some results have been promising, there is no clear evidence to date that
      artesunate reduces mortality in patients with cerebral malaria to any greater
      extent than standard quinine therapy. When given as monotherapy, treatment should
      be continued for at least 5 to 7 days to prevent recrudescence. Combination
      therapy with mefloquine allows artesunate to be administered over 3 days or less,
      with a satisfactory clinical outcome maintained. Although optimal dosages remain
      to be determined, this combination continues to provide the rapid onset of
      clinical effect observed with artesunate monotherapy, but decreases the rate of
      recrudescence to 2% (i.e. radical cure rate of 98%) when used as treatment in
      patients with uncomplicated malaria from areas with a high risk of multidrug
      resistance falciparum malaria. Although assessment of tolerability is complicated
      by the difficulty of distinguishing between disease- and treatment-related
      events, artesunate and artesunate-mefloquine combinations appear to be well
      tolerated in adults and children. Indeed, it is possible that prior
      administration of artesunate may reduce the incidence of mefloquine-induced
      vomiting. Clinical findings to date have not revealed any pattern of resistance
      to artesunate after use of the drug. However, given the history of the
      development of resistance to other antimalarial drugs, the use of artesunate
      should be restricted to areas of multidrug resistance, the drug should be used in
      combination with a longer acting agent such as mefloquine, and it should be used
      in regimens that provide radical cure rates of 90 to 100%. If used according to
      these treatment principles, artesunate will provide a well tolerated and valuable
      addition to the current extremely limited treatment options for multidrug
      resistant falciparum malaria, a widespread parasitic disease associated with
      considerable mortality.

PMID- 8536558
TI  - Epithelitis of a tympanic membrane graft.

PMID- 8536556
TI  - Desflurane. A review of its pharmacodynamic and pharmacokinetic properties and
      its efficacy in general anaesthesia.
AB  - Desflurane is a halogenated ether inhalation general anaesthetic agent with low
      solubility in blood and body tissues, and approximately one-fifth the potency of
      isoflurane. The pharmacodynamic properties of desflurane generally resemble those
      of isoflurane; thus, it produces dose-dependent depression of the central nervous
      and cardiorespiratory systems, and tetanic fade at the neuromuscular junction.
      The alveolar equilibration of desflurane is rapid (90% complete at 30 minutes
      compared with 73% for isoflurane). Both desflurane and isoflurane are distributed
      to various tissues to a similar extent. Desflurane is resistant to chemical
      degradation and undergoes negligible metabolism (approximately equal to 10% of
      that seen with isoflurane). Desflurane 'wash-out' is approximately equal to 2 to
      2.5 times faster than that of isoflurane in the first 2 hours after
      discontinuation of anaesthesia. The low solubility of desflurane facilitates a
      rapid induction of anaesthesia and precise control of the depth of anaesthesia
      (during maintenance). Results from a few clinical studies indicate that emergence
      from desflurane is significantly earlier (by approximately equal to 2 to 6
      minutes) than that from propofol anaesthesia, whereas other studies do not
      concur. In comparison with isoflurane, emergence from desflurane anaesthesia is
      significantly earlier (by 5 minutes) after ambulatory and approximately equal to
      50% earlier (also significant) after nonambulatory surgical procedures. Limited
      comparative studies with halothane or sevoflurane also suggest an earlier time of
      emergence from desflurane anaesthesia. Comparative studies of desflurane and
      propofol, and other inhalation agents, indicate that the times to toleration of
      oral fluids, sitting and discharge from recovery room are similar, regardless of
      the general anaesthetic agent administered. However, some limited data in elderly
      patients (aged > 65 years) suggest that this patient group spends a significantly
      shorter time in the postanaesthesia care unit after desflurane than after
      isoflurane anaesthesia. Differences, if any, in the recovery of cognitive and
      psychomotor functions after desflurane or propofol anaesthesia remain unclear.
      However, in comparison with isoflurane anaesthesia, recovery of these functions
      (up to 45 minutes post-operatively) occurs earlier after desflurane.
      Significantly fewer patients are subjectively impaired (i.e. drowsy, clumsy,
      fatigued or confused) upon recovery from desflurane than from isoflurane
      anaesthesia. Likewise, significantly fewer adult patients are delirious when
      recovering from desflurane than from isoflurane anaesthesia, though in paediatric
      patients delirium is more likely when recovering from desflurane than from
      halothane anaesthesia. Haemodynamic stability during coronary artery surgery is
      as well maintained with desflurane as with isoflurane, and the drug does not
      worsen the adverse postoperative outcomes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8536559
TI  - Bilateral vocal fold polyps.

PMID- 8536560
TI  - Choking spells following septorhinoplasty secondary to displaced nasal packing.

PMID- 8536561
TI  - The non-Caucasian (ethnic or platyrrhine) nose.

PMID- 8536562
TI  - Middle ear effusion--allergy relationships.
AB  - Middle ear effusion (MEE), in its various forms, is one of the most common
      disorders of childhood. There are several possible etiologies, depending on the
      makeup of the effusion. However, the common factor in many middle ear effusions
      is eustachian tube dysfunction, and the role of allergy, although only one of
      many possible causes, is significant. A relatively large number of children with
      MEE are found to have atopic disorders. Nonetheless, allergy treatment alone must
      not preclude the use of conventional medical and surgical therapy. Optimal
      results will be obtained if recurrent or persistent MEE is managed in a
      coordinated manner by the otologist, pediatrician and allergist.

PMID- 8536563
TI  - Experience with percutaneous endoscopic gastrostomy on an otolaryngology service.
AB  - Seventy-one patients have undergone percutaneous endoscopic gastrostomy (PEG) on
      our otolaryngology service. Most commonly, these were neurologically-impaired
      (63%) or head and neck cancer (31%) patients. The PEG procedures were done, in
      almost all instances, in the operating room in conjunction with other indicated
      ORL-HNS procedures such as tracheotomy (71%) or with endoscopy or resection for
      head and neck cancer. The success rate in placement of the gastrostomy was 98%.
      There was one major complication, namely, seeding of the gastrostomy site with
      squamous cell carcinoma from a hypopharyngeal tumor. We conclude that PEG is a
      useful addition to the armamentarium of the head and neck surgeon.

PMID- 8536564
TI  - Anterior ethmoidal glycerol rhizotomy for vasomotor rhinitis.
AB  - The treatment of vasomotor rhinitis by anterior ethmoidal glycerol rhizotomy
      (AEGR) was assessed in 78 patients with a follow-up period ranging from 12 to 15
      months. The reduction of nasal hypersecretion obtained with AEGR was maintained
      over six months. At the final assessment, sixty patients (76.9%) reported
      complete relief of symptoms and are taking no medications; seven (8.9%) were
      improved with minimal drug therapy required for symptom relief; and 11.9% had
      poor results with unsatisfactory control even with medication. Nineteen patients
      required a second treatment because of an initial suboptimal infection or
      recurrence. Apparently, this method offers those patients with vasomotor rhinitis
      a valid option for treatment of clinical symptoms, with the additional benefit of
      experiencing no serious complications when compared with vidian neurectomy.

PMID- 8536565
TI  - Airway obstruction secondary to rhinoscleroma during pregnancy.
AB  - Dyspnea is a fairly common complaint during pregnancy. However, if one excludes
      allergic nasal congestion of pregnancy, upper airway obstruction is a distinctly
      uncommon cause of dyspnea in the pregnant patient. Three cases of laryngeal
      rhinoscleroma in pregnant women requiring tracheostomy for airway management are
      reported. All three delivered healthy infants vaginally. Postpartum, two of the
      three were successfully decannulated, while the third became pregnant again
      before decannulation was accomplished. Treatment options and a review of the
      literature are presented.

PMID- 8536566
TI  - Branchial cleft cyst posterior to the carotid vessels.
AB  - Branchial cleft anomalies may appear as a sinus fistula or cyst. An understanding
      of the developmental embryology and anatomy can predict branchial cleft anomalies
      by the relationship of the corresponding branchial arches that form at the time
      of development. The second branchial cleft anomalies are the most common and may
      be found along a tract from the anterior border of the sternocleidomastoid muscle
      anterior to the carotid vessels and IX and XII. A cyst may form anywhere along
      this tract but most commonly is just lateral to the internal jugular vein
      anterior to the carotid vessels. We describe a patient with a second branchial
      cleft cyst that was posterior to the carotid vessels documented by computed
      tomography. The cyst was found intraoperatively to be clearly posterior to the
      common carotid artery. This case demonstrates the need for an understanding of
      developmental embryology, anatomical landmarks and variations.

PMID- 8536567
TI  - Streptococcal pharyngitis: alternative treatments.

PMID- 8536568
TI  - The EEG in acallosal children. Coherence values in the resting state: left
      hemisphere compensatory mechanism?
AB  - Resting EEG interhemispheric and intrahemispheric coherences (ICoh and HCoh) in
      the theta, alpha and beta bands were studied in 7 patients with agenesis of the
      corpus callosum (5 children, aged 10-14 years, and 2 adults) and 2 groups of sex-
      and age-matched normal children and adults (42 subjects). In patients the ICohs
      (F3/F4, C3/C4, P3/P4, O1/O2) were lower than in the normal sample. The ICoh
      decrease, corresponding with the completeness of commissural agenesis, showed the
      essential role of the corpus callosum in interhemispheric EEG synchronization. A
      remarkable new fact was found, namely lower right hemisphere HCoh in the
      acallosal patients in comparison to the normals, suggesting reduced connectivity
      of the right hemisphere. It is assumed that the deviant HCoh patterns in the
      patients, most pronounced in the beta band, are indicative of compensatory left
      hemisphere mechanisms, accounting for a specific brain plasticity phenomenon in
      acallosal subjects.

PMID- 8536569
TI  - Estimation of gestational maturity of preterm infants by five fetal sonographic
      measurements compared with neonatal EEG and the last menstrual period.
AB  - We previously reported no differences in estimates of gestational maturity
      between a cumulative score based on sonographic/obstetrical measurements and an
      EEG interpretation for healthy preterm neonates. For the present study, a rank
      order among 5 fetal sonographic measurements was used to estimate gestational
      age: head circumference, transcerebellar diameter, biparietal diameter, femur
      length, and abdominal circumference were compared with an electroencephalographic
      estimate and an arithmetic estimate of maturity (i.e., the mother's last
      menstrual period). A fetal sonographic study for each of 13 premature neonates
      (i.e., born at < 32 weeks estimated gestational age) was followed after birth by
      a neonatal EEG recording. EEG and sonographic estimates of maturity were assigned
      without knowledge of other clinical data. The mother's last menstrual period was
      obtained from the medical record. Principal component analysis determined that
      86% of the variance was evenly distributed over the 5 sonographic measurements.
      Using a regression procedure, 61% of the variance (adjusted r2 = 0.61) was
      explained by EEG when compared with fetal sonographic estimates. Only 19%
      (adjusted r2 = 0.19) of the variance was explained by the estimate based on the
      mother's last menstrual period. Optimal subset selection determined that the rank
      order for prediction of gestational maturity among the fetal sonographic
      measurements was as follows: (1) head circumference; (2) transcerebellar
      diameter; (3) biparietal diameter; (4) femur length; (5) abdominal circumference.
      Cranial measurements on fetal sonography (i.e., head circumference,
      transcerebellar diameter, biparietal diameter) compared more closely with EEG
      estimates than non-cranial measurements (i.e., femur length and abdominal
      circumference). In conclusion, neonatal EEG estimates of gestational maturity
      compared more closely with sonographic measurements than estimates based on the
      time of the last menstrual period. These findings will be useful in situations
      when dates of conception are unknown or inaccurate, or when intrauterine growth
      restriction causes discrepancies in growth rates between cranial and non-cranial
      fetal measurements on sonography.

PMID- 8536570
TI  - Dynamics of slow wave activity in narcoleptic patients under bed rest conditions.
AB  - Following a baseline night recording, 9 narcoleptic subjects and 9 sex- and age
      matched control subjects were maintained on 16 h of diurnal sleep deprivation.
      Thereafter subjects were submitted to a 32 h bed rest protocol in a sound- and
      light-attenuated room. The EEG was recorded and processed by a Fast Fourier
      Transform. Narcoleptics did not differ from controls in total sleep time over the
      whole 32 h, but spent more time sleeping during the daytime (DT). In both groups
      slow wave activity (SWA) showed an exponential decaying trend during the first
      night (N1); a similar exponential trend during the second night (N2) was evident
      only in controls. In controls SWA showed a circadian-circasemidian distribution
      that was hardly detectable in nacroleptics. Narcoleptics showed an ultradian
      distribution of SWA with periodic emergence every 4 h during DT and N2. Our data
      confirm that a homeostatic mechanism is evident in narcolpetics when stimulated
      by diurnal sleep deprivation, while circadian and circasemidian mechanisms are
      less evident during DT and N2. These findings suggest a different coupling
      between homeostatic sleep regulating and circadian drives to sleep in
      narcoleptics. Ultradian drives to sleep seem to be predominant in these patients,
      thus probably acting as a means for the avoidance of stressful attempts to
      counteract a weaker waking state maintenance mechanism.

PMID- 8536571
TI  - Longitudinal quantitative EEG study of children with different performances on a
      reading-writing test.
AB  - In a previous paper, using the same test for the evaluation of reading-writing
      abilities, Harmony et al. (1990b) reported that children with severe difficulties
      had more delta in fronto-temporal regions, and this was interpreted as a sign of
      underlying cerebral dysfunction. Children with severe and minor difficulties in
      the test had more diffuse theta absolute and relative powers and less alpha
      relative power. As theta decreases with age, while alpha increases, these results
      suggested that children with minor and severe difficulties in reading had a
      maturational lag with respect to those with normal performance. We conducted this
      study in order to test this hypothesis. Two different EEG records were obtained
      with an interval of 2.58-3.15 years in 49 children classified in 3 groups
      according to their performance in a reading-writing test. Group 1: adequate
      performance for age and degree (control group); group 2: below level performance
      with minor difficulties; and group 3: below level performance, with severe
      difficulties. The mean age of the groups in the first study was 9 years. Absolute
      (AP) and relative powers (RP) in the delta, theta, alpha and beta bands were
      computed for each session. In general, groups 3 and 2 showed greater changes than
      group 1 from session to session. ANOVAs performed by session clearly demonstrate
      many significant differences between groups in the first study, while few
      significant differences in parieto-occipital regions in theta RP were observed in
      the second session. These results point toward a maturational spurt of children
      from groups 2 and 3.

PMID- 8536572
TI  - Cognitive brain potentials and regional cerebral blood flow equivalents during
      two- and three-sound auditory "oddball tasks".
AB  - Ten healthy volunteers were examined with single photon emission tomography and
      99mTc-exametazime. They were studied on 2 occasions, during a 2- and a 3-sound
      auditory discrimination (oddball) task. Twenty healthy volunteers were used as
      controls, studied once at rest. During the 2-tone task there was a bilateral
      posterior (occipito-) temporal and medial frontal activation, a left pericentral
      increase, and posterior cingulate suppression. During the 3-sound task activation
      was again found in posterior (occipito-) temporal, medial frontal cortex, left
      pericentral, with a small non-significant reduction in posterior cingulate
      uptake. Compared with the 2-tone task, there was a trend towards higher activity
      in left medial frontal, right posterior temporal and posterior cingulate cortex
      in the 3-sound task. P3b amplitudes were negatively correlated with posterior
      cingulate tracer uptake during both tasks. Positive correlations with P3b
      amplitudes were found in various frontal and temporal regions. These results are
      consistent with more invasive localisation studies of P3b. Posterior cingulate
      cortex appears to be inhibited during the oddball tasks, the more so, the more
      restricted the range of stimuli, and the greater the task-related recruitment of
      neurones (P3b amplitude). As expected from its more frontal distribution, P3a
      amplitude was positively correlated with anterior cingulate tracer uptake, and
      negatively correlated with temporal cortical activity.

PMID- 8536573
TI  - Bilateral activation of the human somatomotor cortex by distal hand movements.
AB  - We recorded cortical magnetic signals, simultaneously over the whole scalp, from
      6 healthy subjects during 3 motor tasks to track the varying proportion of contra
      vs. ipsilateral activation. The subjects performed self-paced index finger
      flexions, simultaneous flexion of 4 fingers, and a sequence of rapid digit
      movements in different sessions. Index finger and 4-finger movements were
      associated with phasic bilateral dampening of spontaneous 10 and 20 Hz rhythms
      along the central sulcus, starting approximately 1 sec before the movement in the
      contralateral hemisphere. A rebound occurred within 1 sec after the index finger
      and 4-finger flexions; the rapid finger movements resulted in a persistent
      blocking of the rhythms. Averaging with respect to movement onset showed a slow
      bilateral frontal readiness field starting about 0.5 sec prior to motion onset.
      It was followed, within 200 msec after movement onset, by phasic movement-evoked
      fields (MEFs) which were bilateral during the tasks involving several fingers.
      The contra- vs. ipsilateral MEF amplitude ratio C/I decreased from 4.0 during
      index finger movements to 0.6 during rapid finger flexions, reflecting the
      enhanced activation of the ipsilateral primary somatomotor cortex with increasing
      complexity of movement.

PMID- 8536574
TI  - Reactivity of magnetic parieto-occipital alpha rhythm during visual imagery.
AB  - Spontaneous MEG signals were recorded during visual imagery from 13 healthy
      adults with a whole-scalp neuromagnetometer. The parieto-occipital 7-14 Hz alpha
      activity was suppressed strongly while subjects visualized and evaluated letters.
      The act of forming a visual image caused a smaller suppression than did
      inspection of the imaged pattern for a named property. The maximum suppression
      depended on the baseline alpha level and, for the majority of the subjects,
      occurred close to the area with the strongest alpha, showing no systematic
      hemispheric asymmetry. Sources for the alpha activity, modeled with equivalent
      current dipoles, clustered in the parietal and occipital lobes. The strongest
      suppression of the activity occurred near the parieto-occipital sulcus.

PMID- 8536575
TI  - Pain-related somatosensory evoked magnetic fields.
AB  - Somatosensory evoked magnetic fields (SEFs) following painful electrical
      stimulation of the finger were investigated in 5 normal subjects. Equivalent
      current dipoles (ECDs) of deflections shorter than 100 msec in latency were
      located in the primary sensory cortex (SI) in the hemisphere contralateral to the
      stimulated finger following either non-painful or painful stimulation. Two main
      deflections, N100m-P100m and N250m-P250m, were independently identified following
      painful stimulation, although they were not found in SEFs following non-painful
      weak stimulation. ECDs of the N100m-P100m were considered to be located in the
      bilateral second sensory cortices (SII). ECDs of the N250m-P250m were identified
      in the bilateral cingulate cortices and SII, but the intersubject difference was
      large. Therefore, we considered that contralateral SI and bilateral SII were
      initially activated by painful noxious stimulation, and then multiple areas
      including bilateral SII and cingulate cortices were activated. In EEG recordings
      (evoked potentials), no potential corresponding to N100m-P100m was found,
      probably because it was difficult to record activation in SII by EEG recordings.
      The P250 potential which corresponded to the N250m-P250m was clearly identified,
      probably because activation of multiple areas generated large long-duration EEG
      potentials which were maximal around the vertex, unlike MEG recordings.

PMID- 8536576
TI  - The effects of time point alignment on the amplitude of averaged orbital
      presaccadic spike potential (SP).
AB  - Effects of two time-point selection averaging techniques on orbital SP amplitude
      were studied on 10 normal subjects performing horizontal saccades. One technique
      involved averaging from the SP peak, another technique involved averaging from
      the saccadic onset. The time-point selection methods only affected the magnitude
      of SP amplitude but did not interact with experimental conditions. Repeated
      measures analysis of variance showed that SP amplitudes were higher in data
      aligned on SP peak than those aligned on saccadic onset (P < 0.01). No
      significant second order (saccade by degree) or third order (saccade by
      direction) interactions involving averaging method were found (P > 0.05).

PMID- 8536577
TI  - Lumbrical-interosseous latency comparison in the diagnosis of carpal tunnel
      syndrome.
AB  - We examined 66 hands referred with suspected carpal tunnel syndrome (CTS) using
      the second lumbrical-interosseous distal motor latency difference (2LI-DML) as
      well as standard tests: Forty-nine cases of CTS were diagnosed by the standard
      tests, 48 of whom had an abnormal median-ulnar palmar velocity comparison and 48
      an abnormal 2LI-DML. The results of these 2 tests were closely correlated. The
      2LI-DML supported the diagnosis of CTS in all cases except one, where the result
      was borderline. In one suspected case the 2LI-DML was the only abnormality. In 9
      severe cases no median palmar responses could be obtained but an abnormal 2LI-DML
      was found. We conclude that the 2LI-DML is as sensitive as the palmar comparison
      and thus will support the diagnosis of CTS made by standard tests by providing an
      additional abnormality but that its routine use is unlikely to increase the
      diagnostic yield. Its value therefore may be in mild cases where the median-ulnar
      palmar comparison is normal or equivocal and in severe cases where standard test
      responses are unobtainable. It has also proved useful as a quick and simple
      screening test for CTS on the asymptomatic side.

PMID- 8536578
TI  - Motor unit firing behavior in slow and fast contractions of the first dorsal
      interosseous muscle of healthy men.
AB  - The motor unit recruitment threshold and firing rate were evaluated during slow
      and fast contraction of the first dorsal interosseous (FDI) muscle by healthy
      young men. Using a special quadrifilar electrode myoelectric activity was
      recorded during voluntary isometric contraction. Motor unit action potentials
      (MUAPs) were decomposed into individual MUAP trains by the electromyography (EMG)
      signal decomposition technique. Recruitment thresholds of the motor units
      decreased with the increase in the speed of contraction, and there was no
      recruitment reversal despite the increase. In terms of rate coding, the firing
      rates of the motor units increased as the speed of contraction increased;
      however, a high threshold motor unit always had a lower firing rate than a low
      threshold motor unit regardless of the contraction speed. At all contraction
      speeds, recruitment and rate coding may act through the same mechanism. If
      excitation of the motoneuron pool occurs rather than excitation of an individual
      motoneuron, a low threshold motor unit is easier to recruit and fire repetitively
      than a high threshold one. The motor unit firing behavior during fast contraction
      basically may be the same as during slow contraction.

PMID- 8536579
TI  - Intraoperative monitoring during selective posterior rhizotomy: technique and
      patient outcome.
AB  - We evaluated intraoperative electromyographic (EMG) results among 110 pediatric
      patients with spastic cerebral palsy who underwent selective posterior rhizotomy.
      We analyzed surgical outcomes for 60 of these patients who returned for follow-up
      assessment between 4 and 17 months postoperatively. Reduction in muscle tone
      (resistance to passive movement), increased range of motion and improvements in
      functional skills were seen at follow-up. To control for possible changes due to
      development, participation in therapy, or instability of measurements, 30
      rhizotomy patients were evaluated twice during a baseline period of several
      months prior to surgery. No significant changes were found between these two
      measurement sessions during the baseline control period suggesting that the
      rhizotomy surgery itself caused the postoperative improvements. These
      intraoperative EMG monitoring techniques have been adopted at many other centers
      but variations in specific methods and EMG criteria have developed subsequently
      among major hospitals where selective posterior rhizotomy is performed. These
      variations in neurophysiologic methods and recent controversy about the
      usefulness of such intraoperative EMG monitoring created a need for us to publish
      our standard EMG selection technique. We describe here, in detail, methods for
      nerve rootlet testing and selection.

PMID- 8536580
TI  - A new method of estimating the distribution of muscle fiber conduction
      velocities.
AB  - A computer-assisted method of estimating the distribution of muscle fiber
      conduction velocities is described. An electrode array composed of 2 stimulating
      and 4 recording electrodes is used to record surface muscle action potentials
      (MAPs) in response to direct muscle stimulation. The velocity distribution and
      the single muscle fiber action potential (SFAP) are calculated from the recorded
      MAPs by an iterative method of estimation. The estimation is based on the
      assumption that the spatial orientation of each muscle fiber viewed from the
      recording electrodes is the same along the muscle fibers and a MAP is recorded as
      a linear summation of all SFAPs. The accuracy of this estimation is demonstrated
      using simulated MAPs. The method is also tested on MAPs containing simulated
      amplifier noise, stimulus artifact, and errors in distance between electrodes.
      Finally we applied this method to MAP recordings of the biceps brachii in 23
      healthy subjects. The velocity distribution was successfully estimated in 20
      cases. The average of the estimated distributions was smaller than that described
      by previous workers. The reasons for the difference are discussed.

PMID- 8536581
TI  - Reproducibility of a heteronymous monosynaptic reflex in biceps brachii.
AB  - The present study provides normal data for a new technique to assess conduction
      across the C5/C6 segments by recording a heteronymous monosynaptic reflex
      response from the contracting biceps brachii in response to stimulation of the
      median nerve in the cubital fossa. The reflex responses were reproducible and
      symmetrical, with a mean latency of 14.8 msec (S.D. 1.4 msec) and an absolute
      side-to-side differences of 0.5 msec (S.D. 0.29 msec). Latency was significantly
      correlated with both age and height, and multiple regression analysis provided
      the following equation: latency (msec) = 0.091 x height (in cm) + 0.036 x age
      (years) - 1.988. Amplitudes had wide scatter (22-365 microV on the right side)
      and positive skew. An amplitude less than 40% of that for the other side would be
      outside the 90th percentile. Five cases are described to illustrate the potential
      clinical utility of this test. However, whether this reflex is of diagnostic
      value can be answered only by a prospective study comparing it with other routine
      investigations.

PMID- 8536582
TI  - Reliability, specificity and sensitivity of long-term tremor recordings.
AB  - We have developed a method of long-term EMG recording that has proven suitable
      for the quantification of pathological tremor. In the present paper we show that
      the principal parameters of the method (tremor occurrence, tremor intensity,
      tremor frequency) are highly reproducible and that the method is specific and
      sensitive for detection of pathological tremor. Twelve patients with essential
      tremor (ET) and 13 patients with Parkinson's disease (PD) were recorded
      repeatedly on 3 successive days. For each patient group and for each parameter
      the intersubject variability was much larger than the intersubject variability.
      The intraclass correlation coefficient "R" was in the order of 0.9 for each
      parameter and the mean of Pearson's correlation coefficient between successive
      days was also approximately 0.9. Recordings from normal controls demonstrated
      that the method's specificity for pathological tremor is 94.1% and its
      sensitivity is 96%.

PMID- 8536583
TI  - Comparison of various coils used for magnetic stimulation of peripheral motor
      nerves: physiological considerations and consequences for diagnostic use.
AB  - We compared the ability of 4 magnetic coils to activate peripheral nerves in
      healthy subjects. No differences in motor threshold intensities were found
      between the coils, but the intensities needed to elicit maximum compound muscle
      action potential (CMAP) amplitudes were different. For superficial nerves maximum
      CMAPs in comparison with electrical stimulation were usually but not always
      found. CMAPs were at their maximum only when the direction of induced current
      flowed from proximal to distal and when a certain part of the coil was over the
      nerve. Distal nerve stimulation was time consuming. Due to artifacts many stimuli
      were necessary and sometimes no maximum CMAP could be elicited. CMAPs were much
      less sensitive to position changes of the coil than to changes in an electrical
      stimulator. Small circular coils were superior to larger coils in terms of the
      lower intensities necessary to elicit maximum CMAPs, better focusing of the
      stimulus, and less artifacts. For deep nerves amplitudes were always submaximal.
      Coactivation of nearby nerves and underlying muscles was another main drawback
      especially at proximal sites and for coils of large diameter. Despite better
      focusing, double coils are less useful due to their great diameter. Magnetic
      stimulation cannot replace electrical neurography at the moment, even if
      different coils are used at different sites of stimulation.

PMID- 8536584
TI  - Mapping of cortical sites where transcranial magnetic stimulation results in
      delay of voluntary movement.
AB  - Transcranial magnetic stimulation over the motor cortex has been shown to delay
      voluntary movement in man in a reaction time paradigm. In this study, we used a
      focal magnetic coil to stimulate 16 sites over the left hemisphere in 8 normal
      subjects. We measured the delay that occurred in the onset of a ballistic wrist
      flexion response and the size of the motor potentials evoked in the wrist flexors
      by stimulation at each site. The optimal site of stimulation to delay voluntary
      movement coincided with the optimal site to elicit an MEP in the agonist (flexor)
      muscle. However, MEPs were also obtained from some sites at which no delay in
      movement was induced.

PMID- 8536585
TI  - Magnetic transcranial stimulation in non-haemorrhagic sylvian strokes: interest
      of facilitation for early functional prognosis.
AB  - Magnetic transcranial stimulation was applied to 40 patients in the early stage
      of a non-haemorrhagic sylvian stroke. Results were evaluated with regards to the
      clinical outcomes at days 7, 30 and 90. The presence or absence of an early
      response had a critical prognostic significance. Response latency and amplitude
      parameters and the excitation threshold were of little value. Facilitation in
      patients unresponsive at rest was another determinant parameter since 9 out of 10
      such cases ultimately recovered.

PMID- 8536586
TI  - Electrophysiological characteristics of lesions in facial palsies of different
      etiologies. A study using electrical and magnetic stimulation techniques.
AB  - Using magnetic stimulation techniques in addition to conventional electrical
      stimulation, the entire facial motor pathway can be assessed
      electrophysiologically. To study the diagnostic yield of these examinations, 174
      patients with facial palsies of a variety of etiologies were examined (85 Bell's
      palsies, 24 Guillain-Barre syndrome (GBS), 19 Lyme borreliosis, 17 zoster oticus,
      12 meningeal affections, 10 brain-stem disorders and 7 HIV-related facial
      palsies). The facial nerve was stimulated electrically at the stylomastoid fossa
      and magnetically within its canalicular portion. Additionally, the face
      associated contralateral motor cortex was stimulated magnetically. Recordings
      were from the nasalis or mentalis muscle, or both, using surface electrodes.
      Bell's palsy patients showed typically a unilateral local hypoexcitability of the
      facial nerve to canalicular stimulation. In GBS, bilateral latency prolongations
      were frequent, as expected for a myelinic disorder. In contrast, in zoster,
      predominant axonotmesis was unilateral, and in HIV infection sometimes bilateral.
      The method was very sensitive to detect subclinical dysfunctions in meningo
      radiculitis and malignant meningeal diseases, either prior to the onset of palsy,
      or on the contralateral (clinically unaffected) side. It also distinguished
      reliably between central and peripheral facial motor pathway lesions. In our
      experience, these inexpensive and non-invasive electrophysiological techniques
      contribute substantially to the differential diagnosis of facial palsies.

PMID- 8536587
TI  - Percutaneous magnetic coil stimulation of the phrenic nerve roots and trunk.
AB  - We describe a technique of percutaneous magnetic coil (MC) stimulation of the
      phrenic nerve trunk on one side of the neck and phrenic roots over the upper
      cervical vertebral column in 10 normal subjects and 2 patients. We were able to
      obtain compound muscle action potentials (CMAPs) from the diaphragm at two sites
      (xiphoid process and 7th intercostal space) after stimulation of the phrenic
      nerve trunk and roots. We noted that the onset latencies after phrenic root
      stimulation remained fixed despite increasing the stimulus intensity from 50% to
      100% and on moving the MC vertically or laterally, suggesting that stimulation of
      the fastest conducting fibers was occurring at a fixed site, most likely at the
      intervertebral foramina. Absent responses unilaterally in one and prolonged
      latencies to diaphragmatic CMAPs in another patient confirmed phrenic neuropathy
      in these patients.

PMID- 8536588
TI  - Input-output organization in the hand area of the human motor cortex.
AB  - The primate motor cortex consists of efferent zones which receive sensory
      information from a portion of limb in close anatomical relation to the muscle to
      which they project. To investigate a similar input-output relation in humans, we
      studied the effect of tactile stimuli on the size of motor evoked potentials
      (MEPs) elicited by transcranial magnetic and electrical stimulation. For tactile
      stimuli we applied air to the skin. The sizes of MEP of 3 finger muscles (flexor
      pollicis brevis, first dorsal interosseous, and abductor digiti minimi) with and
      without air stimuli were compared. Air stimuli applied to the tip of one finger
      facilitated mainly the magnetically evoked MEP of a muscle attached to that
      finger. A less obvious facilitatory effect was observed when giving stimuli on
      the dorsal aspect of the hand. Air stimuli had no facilitatory effect on
      electrically evoked MEPs. In one subject, there was no facilitatory effect even
      to magnetically evoked MEPs. In this subject, D-waves had the lowest threshold
      for magnetic and electrical stimulation. These results suggested that the effect
      was produced at the cortical level. This effect may correspond to the input
      output relation found in the primate motor cortex.

PMID- 8536589
TI  - Changes of cortical motor area size during immobilization.
AB  - Changes of motor cortex organization after lesions in the nervous system can be
      demonstrated by mapping the motor cortex with transcranial magnetic stimulation.
      We studied cortical plasticity in 22 patients who had a unilateral immobilization
      of the ankle joint without peripheral nerve lesion. The motor cortex area of the
      inactivated tibial anterior muscle diminished compared to the unaffected leg
      without changes in spinal excitability or motor threshold. The area reduction was
      correlated to the duration of immobilization. It could be quickly reversed by
      voluntary muscle contraction. This indicates a functional (and not morphological)
      origin of the phenomenon.

PMID- 8536590
TI  - Postural modulation of the soleus H reflex in young and old subjects.
AB  - The influence of different static postures on the soleus H reflex was assessed in
      15 old (mean age = 76.3 years) and 10 young (mean age = 24.2 years) subjects. H
      reflex and M wave recruitment curves were obtained under 2 randomly administered
      conditions: (1) standing; and (2) prone. Once in place, the recording and
      stimulating electrodes were not removed until the completion of testing, to
      ensure that exact placement was maintained. A 1 msec current pulse was given
      transcutaneously to elicit the H reflex and M response. Static postural sway area
      (cm2) was assessed on a Kistler force platform using custom software (sample rate
      = 50 Hz/15 sec trials). Results demonstrated that the young subjects reduced the
      amplitude of the H reflex from the prone (Hmax/Mmax = 73.6%) to the standing
      (Hmax/Mmax = 59.9%) condition, whereas the old subjects did not (prone = 32.4%,
      standing = 38.2%). However, within the old group, 2 subgroups emerged--those who
      depressed the reflex similar to the young subjects (O-D, n = 6) and those who did
      not depress the reflex (O-ND, n = 9). Furthermore, there were significant
      differences in postural sway scores between the young and old, between the O-D
      and O-ND, but not between the O-D and young groups. These results suggest
      differences in the manner in which young and old subjects modulate the soleus H
      reflex when standing, and support the view that modulation of the stretch reflex
      may be important in the control of static posture.

PMID- 8536591
TI  - Afferent excitation of human motor cortex as revealed by enhancement of direct
      cortico-spinal actions on motoneurones.
AB  - Changes in motor cortex excitability induced by somatosensory afferences were
      evaluated in 5 subjects by testing how the short-latency cortico-spinal effects
      evoked by transcranial magnetic stimulation in flexor carpi radialis (FCR)
      motoneurones were influenced by volleys in median nerve afferent fibres.
      Transcranial magnetic stimulation induced two facilitatory peaks on FCR H reflex,
      the first at a conditioning-test interval of about -3 msec and the second at
      msec, separated by a phase of inhibition. If an electric shock to the median
      nerve at the wrist, 0.8-1 x motor threshold (MT) for thenar muscles, preceded the
      cortical stimulus by 18-25 msec, an increase in size of both facilitatory peaks
      was observed. The increase was partly due to a direct action of the median nerve
      volley on motoneurones. When this contribution was subtracted, two peaks of
      additional facilitation resulted as the effect of combined conditioning.
      Additional facilitation was present even during the short-lasting phase ascribed
      to monosynaptic cortico-spinal excitation of motoneurones, i.e., the first
      millisecond of the earliest facilitatory peak. This result indicates that
      cortical responsiveness to magnetic stimulation had been enhanced by the
      peripheral stimulus. The time course of the excitability changes in motor cortex
      was compared with the cortical somatosensory evoked potentials (SEPs) induced by
      the same peripheral stimulus. Additional facilitation was present immediately
      after the N20 peak of SEPs and lasted 8-10 msec. Additional facilitation had the
      same threshold as N20 (0.6 x MT) and grew in parallel with it when grading the
      afferent stimulus up to 1 MT.

PMID- 8536592
TI  - Soleus H reflex extinction in controls and spastic patients: ordered occlusion or
      diffuse inhibition?
AB  - Extinction of the soleus H reflex at higher stimulus intensities is commonly
      attributed to retrograde conduction of action potentials in motor axons. This
      study was designed to gain further insight into the mechanisms underlying the
      extinction. The decrease of the H reflex was quantified in a group of controls
      and spastic patients, with and without depression of the H response by continuous
      tendon vibration. Response amplitudes were normalized as a percentage of the
      maximal M wave amplitude. Stimuli were normalized as a multiple of the M wave
      threshold. After normalization, the mean M recruitment curves, and similarly the
      fractions of motor axons activated, were equal in each group. In contrast, the
      mean H reflex amplitudes at the M threshold were different. The mean H reflex
      decrease, between 1.0 and 1.5 times the M threshold, was found to be the same
      fraction of the maximal H reflex amplitude in each group. The largest motor
      fibres, belonging to the largest motoneurones, are traditionally thought to have
      the lowest threshold for electrical excitation. Collision or retrograde
      inactivation should therefore preferentially affect the largest motoneurones,
      employed in only the largest H reflexes, at the lowest stimulus intensities. Our
      results are contrary to this hypothesis. Renshaw and/or Ib inhibition is likely
      to play a role in the initial decrease of the H reflex at higher stimulus
      intensities.

PMID- 8536593
TI  - Leg muscle activation during gait in Parkinson's disease: adaptation and
      interlimb coordination.
AB  - Adaptation in leg muscle activity and coordination between lower limbs were
      studied during walking on a treadmill with split belts in one group of
      parkinsonian patients and one of age-matched healthy subjects. Four different
      belt speeds (0.25/0.5/0.75/1.0 m/sec) were applied in selected combinations to
      the left and right leg. While these walking conditions were easily tolerated by
      the healthy subjects, the parkinsonian patients usually reached the limits of
      their walking capabilities. Both groups adapted automatically to a change in belt
      speed within approximately 20 stride cycles. Healthy subjects adapted by
      reorganizing their stride cycle with a relative shortening of duration of support
      and lengthening of the swing phase of the "fast" leg and vice versa on the "slow"
      leg. The patients showed a restricted range of stride frequencies for the various
      belt speeds during normal and split-belt walking with consequent deviations in
      the reorganization of the stride cycle. In both healthy subjects and patients,
      ipsilateral gastrocnemius and contralateral tibialis anterior electromyographic
      (EMG) activity increased predominantly with an ipsilateral increase in belt
      speed. Two main differences were observed in the EMG patterns: (1) In the
      patients leg muscle EMG activity was less modulated and gastrocnemius EMG
      amplitude was small during normal and split-belt walking. However, there was no
      significant difference between the two groups in respect to the reorganization of
      the EMG pattern required for the various split-belt walking conditions. (2) The
      amount of co-activation of antagonistic leg muscles during the support phase of
      the stride cycle was greater in the patients compared to the healthy subjects
      during normal and split-belt walking. It is suggested that reduced EMG modulation
      and recruitment in the leg extensors may contribute to the impaired walking of
      the patients. This in turn is a result of an impaired proprioceptive feedback
      from extensor load receptors. This defective control is partially compensated for
      in parkinsonian patients by a greater amount of leg flexor activation which leads
      to a higher degree of co-activation. Visual input plays a role in the control of
      this increased activation.

PMID- 8536594
TI  - Auditory startle (audio-spinal) reaction in normal man: EMG responses and H
      reflex changes in antagonistic lower limb muscles.
AB  - The audiospinal reaction (ASR) to a 30 msec tone of 90 dB has been studied in 66
      seated healthy volunteers. Electromyographic bursts induced in trapezius (Tra),
      soleus (Sol) and tibialis anterior (TA) have been looked for. Facilitation of Sol
      H reflex has been measured in 21 subjects in terms of delays from delivery of the
      sound. Among the subjects, 11 had a stable TA H reflex whose facilitation was
      compared to that of Sol H. Effects of selective isometric voluntary contraction
      of either Sol or TA were assessed both on EMG responses and H reflex
      facilitation. At rest, only 36% of subjects exhibited a response in Sol at a mean
      latency of 123 msec and 39% in TA at a latency of 119 msec. Responses were seen
      in antagonist muscles in 74% of subjects. Incidence in Tra was 96%. During
      voluntary contraction, the results were not significantly changed either in the
      contracted muscle or its antagonist. H reflex facilitation of both TA and Sol
      started 50 msec after the sound to peak after 75-125 msec and returned to
      baseline values after 250 msec. Extent of Sol H reflex facilitation remained
      similar during voluntary contraction of Sol and TA. It was observed that EMG
      responses were more frequent in subjects with brisk reflexes but not necessarily
      in those who exhibited the largest H reflex facilitation. The results are in
      agreement with assumptions that ASR is mediated through reticulo-spinal pathways
      but do not support the view that it corresponds to a flexor reaction. In addition
      to providing quantitative data for comparisons in pathological cases, they
      suggest differences in the mode of activation of motoneurones by the motor cortex
      and subcortical nuclei.

PMID- 8536595
TI  - Modifications of audio-spinal facilitation during gait in normal man.
AB  - An unexpected loud sound--sufficient to elicit an audio-spinal response in lower
      limb muscles during standing--has been delivered during the gait cycle in 40
      healthy volunteers. Raw EMG bursts were recorded in the right trapezius (Tra),
      and in soleus (Sol) and tibialis anterior (TA) muscles bilaterally before being
      converted into envelope curves which were measured. The results indicated that
      the step cycle was not modified. On the other hand, EMG bursts time-locked to the
      sound appeared in Tra during gait. Audio-spinal responses similar to those seen
      during standing were present during gait only in the flexor TA provided it was
      silent. In Sol, responses were absent regardless of whether it was active or not.
      Some later and not time-locked EMG reinforcements were however seen, provided Sol
      was active. The audio-spinal responses during gait differed thus markedly from
      those seen at rest in the standing position. It is suggested to consider
      intervention of the central pattern generator which is already known to alter
      dramatically the responses to peripheral stimuli during gait. Another possibility
      might be that the descending influences are modified in supraspinal structures
      but this interpretation is less likely as responses are not cyclically modified
      in Tra.

PMID- 8536596
TI  - Inter- and intraobserver variation in the interpretation of electromyographic
      tests.
AB  - This study was undertaken with the aim of evaluating inter- and intraobserver
      variation on the pathophysiological interpretation of individual
      electromyographic (EMG) tests on muscles and nerve segments. Seven physicians
      from 6 European EMG laboratories independently interpreted 81 EMG studies
      comprising 735 muscle tests and 726 tests on nerve segments. Pathophysiological
      conclusions were inferred from findings of these tests without considering
      clinical information. For most combinations of findings, both the inter- and
      intraobserver variations on the interpretation were low, suggesting that common
      criteria for pathophysiological interpretations were used and that these were
      used consistently. For some combinations of findings, however, there was
      disagreement on whether these indicated specific or unspecific pathophysiological
      changes. In particular disagreement on whether findings indicated demyelination
      may be of clinical significance. A large part of the intraobserver variation may
      be explained by a change towards more cautious interpretations during the study
      for most of the physicians. It is concluded that there is a need to seek for
      consensus on the pathophysiological interpretation of individual findings and for
      incentives to ensure consistency in interpretations. The fact that experienced
      physicians changed their ways to interpret findings during the study suggests
      that agreement may be improved globally.

PMID- 8536597
TI  - Variation in performance of the EMG examination at six European laboratories.
AB  - The quality of the EMG examination might be improved by standardization. However,
      knowledge about interlaboratory differences in the performance of the EMG
      examination is a prerequisite for standardization. The aim of this study was to
      describe differences in EMG techniques used and number of muscles and nerves
      examined per patient at 6 European EMG laboratories. The EMG results of 595
      patients were prospectively sampled. The average number of muscles examined per
      patient in different disorders varied from laboratory to laboratory, for example
      from 3.0 to 10.8 muscles in anterior horn cell disorders and from 2.0 to 5.5
      muscles in myopathies. The average number of muscles examined by quantitative EMG
      varied from 0 to 4.3 in anterior horn cell disorders and from 0.0 to 4.5 in
      myopathies. Also the average number of nerve segments examined per patient varied
      from laboratory for example from 2.7 to 17.7 for motor segments and from 3.1 to
      9.0 for sensory segments in polyneuropathies. The laboratories that used needle
      electrodes for nerve conduction studies and quantitative analysis of individual
      motor unit potentials examined a smaller number of muscles and nerves than
      laboratories using surface electrodes for nerve conduction studies and
      qualitative EMG studies. The results of this study may have impact on guidelines
      and examination protocols as well as on quality assurance.

PMID- 8536598
TI  - Facilitatory effect of tonic voluntary contraction on responses to motor cortex
      stimulation.
AB  - To investigate the mechanisms underlying the facilitation of responses to motor
      cortical stimulation produced by tonic voluntary contraction, we studied the
      facilitatory effects in 7 normal volunteers during different levels of muscle
      contraction. Responses were similarly facilitated by voluntary contraction with 3
      forms of stimulation: magnetic cortical, electrical cortical, and foramen magnum
      level stimulation. At a high level of contraction, however, only magnetic
      responses were markedly facilitated. We conclude that the facilitation of
      responses to cortical stimulation induced by tonic voluntary contraction occurs
      mainly at the spinal level, but that cortical excitability changes also
      contribute to the enlargement of magnetic responses in the case of a high level
      of contraction.

PMID- 8536599
TI  - A novel whey to study effects of insulin-like growth factor-I on mammary
      development.

PMID- 8536600
TI  - Induction of lipid peroxidation during steroidogenesis in the rat testis.
AB  - Free radical production and lipid peroxidation are potentially important
      mediators in testicular physiology and toxicology. The cytochrome P450 enzymes of
      the steroidogenic pathway are known to produce free radicals. The present study
      was conducted to elucidate in vivo the gonadotropin regulation of free radical
      mediated lipid peroxidation and the antioxidative defense system in the rat
      testis. GnRH antagonist (Org 30276; 1 mg/kg BW) and testosterone [40-mm SILASTIC
      brand (Dow-Corning) capsules] treatments were used to suppress serum gonadotropin
      levels. As expected, serum LH decreased to a very low level, whereas serum FSH
      decreased only slightly. Testosterone treatment for 8 days decreased the levels
      of the peroxide-metabolizing enzymes, catalase, glutathione peroxidase (GSH-Px),
      and glutathione transferase (-44%, -24%, and -31%, respectively; P < 0.01 for
      all). These changes predominately reflect the interstitial tissue, in which
      catalase and GSH-Px activities were much higher than in the seminiferous tubules.
      Testicular CuZn or Mn superoxide dismutase activities, which were high in the
      seminiferous tubules, were not affected by gonadotropin suppression. The total
      peroxyl radical-trapping capacity of the testis, or its components, vitamin E and
      ubiquinol 9, were not affected either. Lipid peroxidation was decreased after 8
      day treatment, as detected by diminished formation of conjugated dienes and
      fluorescent chromolipids (-30% and -19%, respectively; P < 0.05 for both).
      Similar results of decreasing catalase and GSH-Px activities were found after
      gonadotropin suppression with GnRH antagonist treatment for 2 days or
      testosterone treatment for 5 days. Substitution with hCG, alone or in combination
      with recombinant human FSH, reversed the changes in enzyme activities, whereas
      FSH alone had no effect. After 5-day testosterone treatment, catalase messenger
      RNA expression was studied by Northern hybridization, and it was observed to
      parallel the changes in enzyme activity. The site of free radical production was
      studied by separating interstitial tissue and seminiferous tubules 5 h after hCG
      injection. GSH-Px was induced by hCG only in the interstitial tissue (+28%; P<
      0.01), supporting the hypothesis of free radical production during
      steroidogenesis. Aminoglutethimide, an inhibitor of the P450 cholesterol side
      chain cleavage enzyme, induced extensive lipid peroxidation in the testis.
      Presumably, aminoglutethimide leads to leakage of free radicals from the P450
      enzyme when substrate oxygenation is prevented. In conclusion, the present study
      suggests that physiological LH action in the rat testis causes lipid peroxidation
      and maintains high activities of peroxide-metabolizing enzymes in the
      interstitial tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8536601
TI  - Effects of metformin on tyrosine kinase activity, glucose transport, and
      intracellular calcium in rat vascular smooth muscle.
AB  - Metformin enhances peripheral insulin action and reduces blood pressure in
      hypertensive rats. Our group has previously reported that insulin and insulin
      like growth factor I (IGF-1) attenuate both agonist-induced vascular smooth
      muscle cell (VSMC) contraction and associated increases in cytosolic free calcium
      ([Ca]i). Thus, changes in insulin actions may explain in part metformin's
      vascular effects. However, metformin's mechanism of action at the vasculature had
      not been elucidated. Therefore, the purpose of this study was to determine
      whether metformin evokes alterations in VSMC insulin and IGF-I receptors, glucose
      transport, and/or [Ca]i. We quantitated hormone binding and tyrosine kinase (TK)
      activity in partially purified insulin and IGF-I receptors prepared from
      metformin-treated (100 microM) and control rat aortic VSMC in culture. Glucose
      transport was assessed by 2-deoxyglucose uptake. Metformin exposure for 24 h 1)
      increased basal TK activity (metformin, 3.49 +/- 0.39; control, 1.77 +/- 0.39
      pmol 32P incorporated/mg protein; P < 0.01) without changes in insulin-or IGF-I
      stimulated TK activity, 2) increased 2-deoxyglucose transport in a dose-dependent
      manner, 3) decreased thrombin-induced elevation in [Ca]i (metformin, 10.3%;
      control, 35.3% over basal; P < 0.05), These insulin/IGF-I-like effects of
      metformin may help explain some of its vascular actions.

PMID- 8536602
TI  - Effects of cyclic adenosine 3',5'-monophosphate on chondrocyte terminal
      differentiation and cartilage-matrix calcification.
AB  - We examined the effects of cyclic AMP on terminal differentiation and
      calcification in rabbit growth plate chondrocyte cultures. Dibutyryl cAMP
      (dbcAMP), as well as 8-bromo-cAMP abolished the increases in chondrocyte size,
      alkaline phosphatase activity, type X collagen synthesis, 1 alpha, 25
      dihydroxyvitamin D3 receptor synthesis, the incorporation of 45Ca into insoluble
      material, and the calcium content. All of these occurred in parallel untreated
      cultures during the hypertrophic (terminal) stage. The inhibition of alkaline
      phosphatase by dbcAMP was detectable after 24 h, and this effect was reversible.
      dbcAMP and 8-bromo-cyclic AMP inhibited alkaline phosphatase induction and
      calcification at low concentrations (3-5 microM), whereas 10-30-fold higher
      concentrations were required to stimulate proteoglycan synthesis. These findings
      suggest that cAMP plays a crucial role in suppressing terminal differentiation of
      chondrocyte and cartilage-matrix calcification.

PMID- 8536603
TI  - Somatostatin increases growth hormone (GH) secretion in a subpopulation of
      porcine somatotropes: evidence for functional and morphological heterogeneity
      among porcine GH-producing cells.
AB  - Previous results demonstrate that porcine somatotropes can be separated by
      density gradient centrifugation into low density (LD) and high density (HD)
      subpopulations. In rat, two analog somatotrope subpopulations differ
      morphologically and functionally. In an attempt to determine whether
      morphological differences were also present within LD and HD porcine
      somatotropes, we undertook a quantitative electron microscope study of the
      subcellular organelles of immunoidentified LD and HD somatotropes. In addition,
      to test for the existence of functional differences, cultures of separated HD and
      LD subpopulations were treated for 4 h with or without 10 microM GRF-(1-29)
      and/or 100 microM somatostatin (SRIF), and porcine GH release and intracellular
      content were evaluated using a homologous enzyme immunoassay. Morphometric
      results demonstrate that LD somatotropes are smaller in size (P < 0.05) and
      contain fewer secretory granules (P < 0.05) and more rough endoplasmic reticulum
      (P < 0.05) than HD somatotropes. In terms of secretion, LD somatotropes showed a
      classical response; GRF increased GH release 1.7-fold (n = 6; P < 0.05) over the
      control value, whereas treatment with SRIF alone did not affect basal GH release
      in this subpopulation, but partially blocked GRF-induced GH release. HD
      somatotropes responded to GRF with a similar 1.7-fold increase in GH release.
      However, SRIF administered alone or in combination with GRF exerted a paradoxical
      stimulatory effect on HD somatotropes (2.15- and 2.12-fold over control value,
      respectively; n = 6; P < 0.05). These results demonstrate that the porcine
      somatotrope population is composed of two major subpopulations that display a
      distinctive pattern of ultrastructural organization and a markedly divergent
      secretory response to in vitro SRIF treatment.

PMID- 8536604
TI  - Parathyroid hormone stimulation of calcium transport is mediated by dual
      signaling mechanisms involving protein kinase A and protein kinase C.
AB  - PTH stimulates calcium absorption by renal distal convoluted tubules. The PTH
      receptor is capable of coupling to adenylyl cyclase and phospholipase C. However,
      it is not known whether the actions of PTH require activation of both pathways.
      Three approaches were taken to identify the signaling pathways responsible for
      stimulating calcium entry in distal convoluted tubule cells: second messengers
      formed in response to PTH were identified, the effects on calcium uptake of
      inhibiting protein kinase A (PKA) or protein kinase C (PKC) with chemical or
      peptide blockers were determined, and calcium transport was reconstituted by the
      addition of exogenous second messengers. PTH increased cAMP formation in primary
      cultures of mouse distal and proximal tubule cells. However, PTH stimulated
      inositol trisphosphate formation only in proximal tubule cells. Blocking PKA with
      Rp-cAMPS or the cAMP-dependent protein kinase inhibitor inhibited PTH-stimulated
      Ca uptake. Likewise, the PKC inhibitors, calphostin C and PKC pseudosubstrate,
      inhibited PTH-induced calcium uptake. Addition of forskolin (30 nM) or phorbol 12
      myristate 13-acetate (10 nM) alone had no effect on Ca uptake. However, when
      added in combination, Ca uptake was stimulated to nearly the same extent as with
      concentrations of PTH that maximally stimulate calcium transport. We conclude
      that stimulation of calcium uptake by distal convoluted tubule cells requires
      activation of both PKA and PKC.

PMID- 8536605
TI  - Alpha 1-adrenergic stimulation of isolated rat atria results in discoordinate
      increases in natriuretic peptide secretion and gene expression and enhances Egr-1
      and c-Myc expression.
AB  - We studied the effects of alpha1-adrenergic stimulation on atrial natriuretic
      factor (ANF) and brain natriuretic peptide (BNP) secretion and gene expression in
      isolated right atria. The early-response genes Egr-1 and c-myc were also studied
      as potential markers of transcriptional activation after alpha1-adrenergic
      stimulation. Isolated right atria from rats were stimulated for up to 8 h by the
      alpha1-adrenergic agonist phenylephrine (PE). PE at 10, 50, or 100 microM
      stimulated the secretion of immunoreactive (ir) ANF, beginning at 0.5 h and
      peaking after 1.5 h, IrANF secretion remained significantly elevated for 8 h with
      100 microM PE, reached control levels after 5 h with 10 microM PE, and after 6 h
      microM PE with 50 microM PE, PE at 50 or 100 microM stimulated irBNP secretion
      after 15 min, which peaked at 1 h, and thereafter remained above control levels.
      Calculation of irANF/irBNP ratios revealed that their stimulated secretion was
      not coregulated. PE caused significant changes in steady state transcript levels
      for the genes studied. After 6 h, 50 microM PE caused a 49% increase in ANF
      messenger RNA (mRNA) levels. BNP mRNA levels were increased by 135% after 6 h and
      by 77% after 8 h. Egr-1 mRNA levels were increased by 81% after 4 h, 167 after 6
      h, and 40% after 8 h of treatment, mRNA levels of c-myc were increased by 49%
      after 4 h and 53% after 6 h. PE-induced increases in secretion and gene
      expression were inhibited by the alpha1-adrenergic receptor antagonist prozosin
      (10 microM). We conclude that both ANF and BNP secretion from atria can be
      stimulated by PE, and that their secretion is not coregulated. The kinetics of
      enhanced natriuretic peptide gene expression and secretion did not change in
      parallel, suggesting that these processes are not acutely coordinated. The
      enhanced expression of Egr-1 and c-myc suggests that they may be involved in the
      modulation of atrial gene expression in response to alpha1-adrenergic
      stimulation. The results presented suggest that compensatory adrenergic
      activation such as those seen in several clinical entities may be one of the
      factors that provide long-term enhanced natriuretic peptide production, thus
      contributing to the maintenance of cardiovascular homeostasis.

PMID- 8536606
TI  - Autocrine and/or paracrine action of vasoactive intestinal peptide on thyrotropin
      releasing hormone induced prolactin release.
AB  - Several in vitro studies have demonstrated that vasoactive intestinal peptide
      (VIP) modulates basal PRL release in normal and hypothyroid anterior pituitary
      (AP) cells through an autocrine or paracrine action. As thyroid hormone is an
      important factor in the regulation of pituitary VIP synthesis and secretion, we
      analyzed the influence of the absence of thyroid hormone on basal PRL release in
      vitro to study whether the release of PRL induced by TRH might be mediated by a
      local action of pituitary VIP. When normal AP cells were cultured in a medium
      supplemented with a near-physiological concentration of free T2 (0.5 nM), basal
      PRL and VIP release decreased and PRL secretion was not altered by the blockade
      of VIP action. This finding allowed us to establish the culture conditions in
      which basal PRL secretion is apparently not under VIP influence. Consequently, we
      were able to study whether pituitary VIP may be implicated in TRH-induced PRL
      release. TRH (100 nM) increased PRL and VIP release in a parallel manner and
      decreased PRL and VIP intracellular content in incubations from 15-180 min. When
      AP cells wee incubated simultaneously with TRH and a VIP receptor antagonist, TRH
      induced PRL release decreased when incubation lasted more than 30 min, whereas
      the depletion of PRL intracellular content induced by TRH was unchanged. TRH also
      slightly increased VIP messenger RNA levels at 3 and 24 h, but PRL messenger RNA
      levels were not modified. These data demonstrate that pituitary VIP participates
      in in TRH-induced PRL release and that the effect of thyroid hormone on basal
      pituitary VIP secretion should be borne in mind when studies on its effect,
      through autocrine and/or paracrine mechanisms, on PRL release stimulated by PRL
      releasing factors are conducted.

PMID- 8536607
TI  - Effect of aging on insulin receptor, insulin receptor substrate-1, and
      phosphatidylinositol 3-kinase in liver and muscle of rats.
AB  - Insulin stimulates the tyrosine kinase activity of its receptor, resulting in the
      phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1),
      which, in turn, associates with phosphatidylinositol 3-kinase (PI 3-kinase),
      thereby activating the latter. Aging is associated with insulin resistance, but
      the exact molecular mechanism is unknown. In the present study, we examined the
      levels and phosphorylation status of the insulin receptor and IRS-1 as well as
      the association between IRS-1 and PI 3-kinase in the liver and muscle of 2-, 5-,
      12-, and 20-month-old rats. There were no changes in the insulin receptor
      concentration in the liver and muscle of rats 2-. 5-, 12-, and 20-month rats.
      There were no changes in the insulin receptor concentration in the liver and
      muscle of rats 2-20 months old, as determined by immunoblotting using antibody to
      the COOH-terminus of the receptor. However, insulin stimulation of receptor
      autophosphorylation, as determined by immunoblotting with antiphosphotyrosine
      antibody was reduced by 25% (P < 0.05) in the liver and muscle of rats at 20
      months. Interestingly, IRS-1 protein levels decrease at an early stage (5 months)
      by 58 +/- 9%, (P < 0.01) and remained at low levels thereafter in muscle, but not
      in liver. In samples previously immunoprecipitated with anti-IRS-1 antibody and
      blotted with antiphosphotyrosine antibody, there were 60 +/- 9% (P < 0.001) and
      92 +/- 4% (P < 0.001) decreases in the insulin-stimulated IRS-1 association with
      PI 3-kinase was decreased by 70 +/- 2% in the liver and muscle, respectively, of
      20-month rats. The insulin-stimulated IRS-1 association with PI 3-kinase was
      decreased by 70 +/- 2% in the liver (P < 0.001) and by 98 +/- 3% (P < 0.001) in
      the muscle of 20-month-old rats, with no change in the PI 3-kinase protein
      levels. The phosphotyrosine-associated PI 3-kinase activity after insulin
      stimulation was dramatically reduced in liver and muscle of 20-month-old rats
      compared to that in 2-month-old rats. Finally, by immunoprecipitation, the
      detection of insulin-stimulated IRS-2 phosphorylation followed the same pattern
      as that for IRS-1 in both liver of 2- and 20-month-old rats. These data suggest
      that changes in the early steps of insulin signal transduction may have an
      important role in the insulin resistance observed in old animals.

PMID- 8536608
TI  - Developmental expression of a candidate mullerian inhibiting substance type II
      receptor.
AB  - We have isolated a candidate Mullerian inhibiting substance (MIS) type II
      receptor complementary DNA from an embryonic rat urogenital ridge library and
      have studied its binding to MIS, its developmental pattern of expression and
      tissue distribution. By in situ hybridization with a full-length riboprobe, the
      receptor is expressed in the mesenchymal cells surrounding the Mullerian duct at
      embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat
      fetal gonads. Expression of the messenger RNA was also seen in the granules cells
      and seminiferous tubules of pubertal gonads. Northern analysis revealed that the
      MIS type II receptor messenger RNA is highly expressed in embryonic, pubertal,
      and adult testes and ovaries, as well as in the gravid uterus. The timing of
      expression in the gonads of both sexes was also analyzed by Northern analyses
      that showed high levels of expression at the time of Mullerian duct regression,
      much lower levels neonatally and prepubertally and then increased expression
      again with sexual maturation. The tissue and developmental specificity of
      expression of this receptor, which make it likely that this is the functional MIS
      type II receptor, can be used to advantage in therapeutic targeting strategies
      and to decipher the function of MIS in the gonads.

PMID- 8536609
TI  - Transforming growth factor-beta inhibits ovarian 17 alpha-hydroxylase activity by
      a direct noncompetitive mechanism.
AB  - Transforming growth factor-beta1 (TGF-beta1) inhibits theca-interstitial cell
      (TIC) androgen biosynthesis while enhancing progesterone production without
      altering P45017 alpha protein content. The purpose of the present study was to
      define the mechanism of TGF-beta 1 inhibition of ovarian androgen production by
      determining the effects of TGF-beta 1 on steroidogenic enzyme messenger RNA
      (mRNA) expression and 17 alpha-hydroxylase activity in TIC in vitro. TIC isolated
      from hypophysectomized immature rat ovaries by Percoll gradient centrifugation
      were cultured with and without LH and TGF-beta 1 up to 6 days. At various times,
      cytoplasmic mRNA was extracted from the TIC, and P450scc, 3 beta-HSD and P450(17
      alpha) mRNA were measured by specific assays, using RT-PCR. Treatment with TGF
      beta 1 alone (0.1-100 ng/ml) had no effect on mRNA expression at 2 days but
      increased P450scc and 3 beta-HDS mRNA at 4 days. TGF-beta did not alter the LH
      stimulation of P450scc and 3 beta-HSD mRNA up to 6 days but caused a modest (2.5
      fold) increase in P450 (17 alpha) mRNA at 2 days. Specificity studies with
      inhibin-A (30 ng/ml), activin-A (100 ng/ml), and MIS (300 ng/ml) demonstrated
      that the effects of TGF-beta 1 were unique within this family of peptides. We
      next examined the effect of TGF-beta 1 on 17 alpha-hydroxylase activity. Kinetic
      analysis revealed that the 17 alpha-hydroxylase enzyme has an apparent Michaelis
      Menten constant of 3.42 mumol/liter and maximum velocity of 0.23 pmol/min x mg
      protein. TGF-beta 1 inhibited 17 alpha-hydroxylase activity by a noncompetitive
      mechanism with an apparent inhibin constant (Ki) of 46.4 pM. The results of our
      studies demonstrate that TGF-beta 1 directly inhibits TIC androgen production by
      a noncompetitive mechanism. This novel mechanism may be important in preventing
      excessive androgen production in developing ovarian follicles without preventing
      differentiation of the TIC.

PMID- 8536610
TI  - Production and characterization of WEG-1, an epidermal growth factor/transforming
      growth factor-alpha-responsive mouse uterine epithelial cell line.
AB  - Uterine epithelial cells (UEC) isolated from 6-week-old CF-1 mice were
      immortalized using retroviral-mediated transfection of SV40 large T-antigen. One
      line, WEG-1, retained epithelial morphology and reacted with antibodies to
      cytokeratins 18, 19, laminin, fibronectin, and beta-catenin. In addition, WEG-1
      cells displayed strong nuclear immunoreactivity to SV40 large T-antigen,
      confirming integration of the retrovirus vector and expression of this gene. WEG
      1 cells were negative for nonepithelial markers such as desmin and factor 8. WEG
      1 cells did not proliferate in serum-free medium; however, addition of 0.5% FBS
      supported proliferation to the same extent as 10% FBS. Addition of 50 ng/ml
      epidermal growth factor to medium containing 0.5% charcoal-stripped FBS restored
      proliferation comparable with 0.5% whole FBS. Epidermal growth factor or
      transforming growth factor-alpha (50 ng/ml), but not transforming growth factor
      beta, leukemia-inhibiting factor, or fibroblast growth factor, induced the
      secretion of three proteins (M(r) approximately to 158K, 148K, and 36K).
      Comparison of protein secretions of WEG-1 cells and UEC showed shared as well as
      distinct bands. Like UEC, WEG-1 cells secreted PGF2a and PGE2 and expressed PG GH
      synthase-2. Unlike UEC, WEG-1 cells showed no apical/basal preference for either
      uptake of methionine or secretion of proteins. The absence of immunoreactive E
      cadherin or zona occludens-1 was consistent with the absence of cell polarity in
      WEG-1 cells. Primary UEC, which polarize in vitro, do not support blastocyst
      attachment. WEG-1 cells, although not polarized in vitro, also exhibited delayed
      blastocyst attachment compared with nonuterine cell lines, suggesting that WEG-1
      cells partially retained some aspects of UEC function relevant to embryo
      attachment. WEG-1 cells expressed messenger RNA for Muc-1, an UEC mucin suggested
      to have antiadhesive properties. Furthermore, WEG-1 cells did not display high
      affinity heparin binding sites, an activity associated with embryo attachment.
      WEG-1 cells may provide a model for studying various aspects of UEC function and
      murine embryo attachment.

PMID- 8536611
TI  - Identification and cellular localization of thyrotropin-releasing hormone-related
      peptides in rat testis.
AB  - Endogenous TRH-like products were analyzed in rat testis using a TRH enzyme
      immunoassay coupled to molecular sieve filtration and HPLC identification. Of the
      three immunoreactive peptides detected, the two major forms exhibited the same
      chromatographic properties as synthetic TRH and pGlu-Phe-Pro-NH2. These peptides
      accounted respectively for 33% and 54% of the total TRH immunoreactivity in the
      testis. In rat serum, HPLC analysis showed the presence of only one
      immunoreactive peak with a retention time similar to that of authentic TRH.
      Ethylene dimethanesulfonate treatment of adult rat was used to assess the effect
      of Leydig cell destruction on the TRH immunoreactivity content. The concentration
      of the three TRH immunoreactive peptides fell gradually after treatment and
      reached a minimum at day 21, where a marked decrease (98%) was observed. At day
      41, the regeneration of Leydig cells was achieved, as shown by histochemistry and
      measurements of serum testosterone and testicular weight. However, no restoration
      of the TRH immunoreactive content was achieved, the three TRH-related peptides
      being only detectable in trace amount. On the other hand, no significant change
      in hypothalamic levels of TRH was observed at any treatment time, indicating that
      hypothalamic TRH biosynthesis was not influenced by testosterone. By using the
      indirect immunofluorescence technique, TRH immunoreactive cells were found in the
      interstitial space of the testis. These results suggest that Leydig cells are the
      only source of authentic TRH and TRH-like peptides in the rat testis. A
      paracrine, or autocrine role for these products is suggested.

PMID- 8536612
TI  - Molecular cloning of a type A chicken corticotropin-releasing factor receptor
      with high affinity for urotensin I.
AB  - The hypothalamic-pituitary-adrenal axis is an essential physiological system in
      many species. CRF, the major neuropeptide regulating ACTH secretion, is highly
      conserved in its primary sequence. Evolutionary conservation of the CRF sequence
      suggests that the CRF receptor (CRF-R) complementary DNA and examined its
      properties. The avian CRF-R complementary DNA encodes a 420-amino acid protein
      that is 87-88% identical to those of human, rat, and mouse. Most sequence
      divergence occurs in the putative signal peptide and the extracellular amino
      terminus of the receptor. Five additional amino acids are inserted in the amino
      terminus of the cCRF-R. When expressed in COS-7 cells, the cCRF-R binds the CRF
      and urotensin I radioligands with high affinities. Urotensin I competes for
      binding to the chicken CRF-R, expressed in COS-7 cells, with an apparent affinity
      20 times higher than that of CRF. Both urotensin I and sauvagine were more
      effective in stimulating cAMP accumulation in COS-7 cells transfected with the
      cCRF-R than CRF. The effects of CRF and urotensin I on inositol phosphate
      accumulation were also tested. Urotensin I was an effective as CRF in stimulating
      inositol phosphate accumulation in COS-7 cells transfected with the cCRF-R. These
      data suggest that the sequence of the CRF-R is highly conserved from avian to
      mammalian species and that, despite its high sequence homology to the type A
      mammalian CRF-R, the ligand binding properties of cCRF-R are similar to those of
      the type B CRF-R i.e. a higher affinity for urotensin I than for CRF.

PMID- 8536613
TI  - A role for trkA nerve growth factor receptors in mammalian ovulation.
AB  - Several members of the neurotrophin (NT) family, including nerve growth factor
      (NGF), NT-3, and NT-4/5, are expressed in the mammalian ovary. As their
      respective receptor tyrosine kinases are also found in the gland, the possibility
      exists that NTs act directly on the gonads to exert effects unrelated to their
      support of the ovarian innervation. We now report that trkA, the NGF receptor
      tyrosine kinase, is involved in the acute activational process that leads to the
      first ovulation. The trkA gene becomes transiently expressed in periovulatory
      follicules at the time of the first preovulatory surge of gonadotropins at
      puberty; the increase in trkA messenger RNA (mRNA) content is dramatic ( > 100
      fold), but transient (approximately 9 h). No such changes in trkB or trkC mRNA
      were observed; the abundance of these mRNAs, which encode the receptor tyrosine
      kinase for NT-4/5 and brain-derived neurotrophic factor, and NT-3, respectively,
      remained at very low levels throughout puberty. In vivo and in vitro experiments
      demonstrated that the activation of trkA gene expression is brought about by the
      proestrous discharge of LH. The increase in trkA mRNA levels is mainly localised
      to cells of the follicular wall and interstitial tissue of the ovary. NGF mRNA
      abundance also increases at proestrus, with peak values detected about 5 h before
      ovulation; as in the case of trkA mRNA, NGF mRNA was found in thecal-interstitial
      cells. Both trkA and NGF protein, detected by immunohistochemistry, were
      localized to this same ovarian compartment. Interleukin-1 beta (IL-1 beta), a
      putative mediator of LH action, enhances both trkA and NGF gene expression in
      ovarian cells, an effect prevented by IL-1ra, a natural IL-1 beta receptor
      antagonist. Il-1 beta also stimulates PGE2 release, and this effect was inhibited
      by both NGF antibodies and a trk receptor blocker, NGF antibodies administered in
      vivo attenuated the increase in ovarian PGE2 synthesis that antedates ovulation.
      Immunoneutralization of NGF action or pharmacological blockade of trk tyrosine
      kinase activity targeted to one ovary resulted in the ipsilateral inhibition of
      ovulation. The remarkably narrow time frame of trkA gene activation at the
      completion of follicular growth suggests that NGF acting as a
      neuroendocrinotrophic factor in a developmentally restricted manner contributes
      to the acute cytodifferentiation process that leads to the first ovulation in
      mammals.

PMID- 8536614
TI  - Decreased brown fat markedly enhances susceptibility to diet-induced obesity,
      diabetes, and hyperlipidemia.
AB  - Previous studies have indicated that rodents are relatively resistant to diet
      induced obesity and that this resistance may be mediated in part by the capacity
      for diet-induced thermogenesis in brown adipose tissue (BAT). To test this
      hypothesis, we fed UCP-DTA transgenic with toxigene-mediated ablation of BAT and
      their control littermates a "Western diet" [21% (wt/wt) fat] or normal mouse chow
      [6.5% (wt/wt) fat]. The diets were begun at weaning (19 days old). At the age of
      12 weeks, transgenic mice receiving the Western diet were markedly obese. The
      increased body weight and total body lipid content were significantly greater in
      transgenic mice receiving the Western diet than were the additive individual
      effects of Western diet (in control mice) and decreased BAT (in chow-fed mice),
      suggesting a synergistic interaction between diminished BAT and diet. A
      synergistic effect of Western diet and BAT ablation was also observed for morbid
      metabolic complications, such as insulin resistance, hyperglycemia, and
      hyperlipidemia. These metabolic changes were accompanied by increased expression
      of tumor necrosis factor-alpha and decreased expression of GLUT4 and beta 3
      adrenergic receptor messenger RNA levels in white adipose tissue of UCP-DTA
      transgenic mice receiving the Western diet compared to those in the other
      experimental groups. As previously described, transgenic mice with diminished
      brown fat are hyperphagic. Of note, the degree of hyperphagia in transgenics
      compared to controls was similar whether the animals were fed chow or a Western
      diet. Thus, the synergistic effect of Western diet on obesity in transgenic mice
      was not mediated by a further stimulation of food intake. Overall, this study
      demonstrates the existence of a synergistic interaction between decreased BAT and
      Western diet to cause marked obesity and its accompanying disorders, such as
      insulin resistance and hyperlipidemia, and gives further support for the view
      that an important function of BAT is protection from diet-induced obesity,
      diabetes, and insulin resistance.

PMID- 8536615
TI  - Regulation of mitogen-activated protein kinase in the pars tuberalis of the ovine
      pituitary: interactions between melatonin, insulin-like growth factor-1, and
      forskolin.
AB  - The pars tuberalis (PT) of the anterior pituitary is notable for the expression
      of levels of melatonin receptors that consistently exceed those in all other
      tissues in mammals. For this reason and because of its anatomical position, it
      has been suggested that the PT may play a role in seasonal reproductive
      responsiveness. However, no data have been forthcoming on the nature of the
      melatonin-responsive cells in this tissue or on the interaction of melatonin with
      other hormonal signals in the control of PT cells. A number of recent studies
      have reported that the tubero-infundibular region of the pituitary in several
      species contains binding sites for insulin-like growth factor-1 (IGF-1). The
      present study, therefore, sought to address the question of whether functional
      receptors for IGF-1 exist in the ovine PT (oPT). Primary cultures of cells from
      the oPT contained a widespread distribution of cells staining positively with a
      monoclonal antibody to the human IGF-1 receptor, with the strongest staining
      occurring over the small phase-bright cells that predominate in this culture
      system and are thought to constitute the melatonin-responsive cell type. As a
      functional assay for responsiveness to IGF-1, primary cultures of oPT cells were
      assayed for activation of mitogen-activated protein kinase (MAPK) using a
      previously validated phosphotransferase assay. Cytosolic extracts from PT cells
      treated with IGF-1 (100 pM-10 nM) caused a dose-dependent increase in the rate of
      phosphorylation of myelin basic protein; in contrast, treatment with melatonin
      had no significant effect on myelin basic protein phosphorylation. Immunostaining
      of Western blots of PT cell extracts with a pan-extracellular regulated kinase
      antibody demonstrated that both p42 and p44 MAPK are strongly expressed in this
      tissue. To confirm that the effects observed in the cytosol assay were indeed
      attributable to increased activation of p42/p44, gel renaturation assays of
      protein kinase activity were performed. These experiments revealed that IGF-1 (10
      nM) and forskolin (1 microM) were both potent activators of 42- and 44-kDa
      moeities; however, neither of these agents had any significant effect on the
      phosphotransferase activity associated with several other higher molecular weight
      kinases also detected by the gel-renaturation assay procedure. Melatonin (10 nm)
      was consistently found to be a highly potent inhibitor of the activation of MAPK
      induced by forskolin; in contrast, melatonin did not inhibit the activation of
      MAPK induced by IGF-1.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8536616
TI  - Tamoxifen-induced proto-oncogene expression persists in uterine endometrial
      epithelium.
AB  - The use of the antiestrogen tamoxifen for breast cancer management, although
      generally well tolerated, is linked to an increase in uterine pathologies in a
      high number of postmenopausal women receiving the drug. This effect is thought to
      be due to estrogenic stimulation of the uterine endometrium by the antiestrogen;
      however, the molecular mechanism underlying the uterotrophic activity of
      tamoxifen and the uterine cellular compartments that respond to the drug have not
      been clearly established. In this study, we determined which of the several
      uterine tissues (myometrium, stroma, and luminal and glandular epithelium)
      demonstrated chronic overexpression of c-fos and the jun proto-oncogenes in
      response to tamoxifen. Uteri from tamoxifen-treated, castrated rats were examined
      histologically, and cell type-specific expression of c-fos, c-jun, jun-B, and jun
      D was assessed using in situ hybridization. Treatment with tamoxifen resulted in
      uterine luminal and glandular epithelial hypertrophy and basally located nuclei
      by 36 h. Extreme uterine glandular and luminal epithelial cell hypertrophy
      persisted 7 days after administration of the drug. Expression of c-fos and jun-B
      messenger RNA was first detected in the luminal and glandular epithelial at 12-36
      h post tamoxifen injection. Seven days after tamoxifen treatment, c-fos and jun-B
      messenger RNA levels were lower but still evident in the uterine endometrial
      epithelium. Tamoxifen completely repressed constitutive expression of c-jun in
      the uterine luminal epithelial cells by 12 h but, unlike estrogen, did not induce
      c-jun expression in the uterine myometrium. Expression of jun-D in the uterine
      glandular and luminal epithelia was observed at 12 h but not at 24 h post
      tamoxifen. These results support our working hypothesis that persistent
      overexpression of cellular oncogenes c-fos and jun-B in the uterine endometrial
      epithelium may contribute to the molecular mechanism underlying the uterine
      toxicity associated with chronic tamoxifen treatment.

PMID- 8536617
TI  - Calcium-mobilizing insulin secretagogues stimulate transcription that is directed
      by the cyclic adenosine 3',5'-monophosphate/calcium response element in a
      pancreatic islet beta-cell line.
AB  - In pancreatic beta-cells, calcium is required for insulin secretion, but can also
      stimulate gene transcription. High potassium-induced membrane depolarization and
      calcium influx have previously been shown to activate kinases that phosphorylate
      and thereby activate the transcription factor cAMP response element (CRE-binding
      protein (CREB) binding to CREs. It is unknown, however, whether hormones and
      neurotransmitters can activate this mechanism. Arginine vasopressin (AVP),
      bombesin, and acetylcholine potentiate glucose-induced insulin secretion and are
      known to raise cytosolic calcium levels through binding to cell surface receptors
      that activate phospholipase C. The effect of AVP on CRE-directed transcription
      was examined in the beta-cell line HIT. AVP (0.1-100 nM) stimulated gene
      transcription after transient transfection of a reporter gene that was placed
      under the transcriptional control of a CRE. This effect was inhibited by a
      vasopressin V1 receptor antagonist and depended on calcium influx and calcineurin
      phosphatase activity. By immunoblots with antiphospho-CREB antibodies and by
      using a Gal4-CREB fusion protein, it was shown that AVP induces the
      phosphorylation and activation of CREB. Like AVP, bombesin (100 nM) and the
      muscarinic agonist carbachol (200 microM) stimulated CRE-mediated transcription.
      These results show that calcium-mediating insulin secretagogues can activate
      CREB/CRE-directed transcription in HIT cells, offering a mechanism by which these
      secretagogues could produce long term effects on beta-cell function, changing the
      pattern of gene expression.

PMID- 8536618
TI  - Examination of steroid-induced changes in LHRH gene transcription using 33P-and
      35S-labeled probes specific for intron 2.
AB  - We previously demonstrated that estrogen, but not progesterone, induces a
      increase in LHRH messenger RNA levels between 0800 and 1200 h in numerous of the
      rostral preoptic area/organum vasculosum of the lamina terminalis (rPOA/OVLT). To
      determine whether these changes are a result of increased transcription, we used
      in situ hybridization histochemistry to examine the temporal effects of estradiol
      (E2) and progesterone on cellular levels of intron-2-containing LHRH
      heteronuclear RNA transcripts. To make our method sufficiently sensitive to
      detect changes in these levels, we used 33P/35S probes to minimize both
      background and grain stacking over labeled cell nuclei. We found that levels of
      LHRH heteronuclear RNA rose between 0800 and 1000 in OVX, E2-treated rats,
      remained elevated at 1200 h, and declined by 1400 h. Progesterone did not affect
      these E2-induced changes. Our results suggest that an E2-dependent signal
      initiates LHRH gene transcription in neurons of the rPOA/OVLT hours before LHRH
      release begins and that progesterone does not affect this signal.

PMID- 8536619
TI  - Follistatin-activin complexes in human serum and follicular fluid differ
      immunologically and biochemically.
AB  - Follistatin (FS) is the principle high affinity activin-binding protein in
      tissues such as the pituitary and ovary as well as in serum. In addition, the
      activin-binding peaks identified after gel filtration of serum or human
      follicular fluid (hFF) exhibited high affinity and low reversibility binding
      kinetics, with higher concentrations in hFF than serum. This extremely low
      reversibility was also observed for recombinant human follistatin 288 (rhFS288)
      under a variety of incubation conditions, further supporting the identification
      of the serum and hFF activin-binding proteins as FS. Using enhanced resolution
      gel filtration, immunoprecipitation with monoclonal antibodies to rhFS288, and
      sulfated carbohydrate binding, activin-FS complexes in hFF and serum differed.
      The activin-FS complex in hFF elutes at approximately 200-300 kDa, is
      immunoprecipitated by anti-hFS288 monoclonal antibodies, and binds to sulfate
      Cellufine matrix, all characteristics similar to those of recombinant human
      FS288. In contrast, the activin binding peak in human serum elutes at an apparent
      Mr of 60-70 kDa, is no precipitated by anti-rhFS288 monoclonal antibodies, and is
      weakly bound by sulfate Cellufine matrix, characteristics shared by rhFS315
      conditioned medium. As the forms of FS that bind sulfate-containing matrices also
      bind to cell surface proteoglycans, the molecular differences reported here for
      serum and hFF activin-binding proteins have implications for potential tissue
      specific forms of FS that may well have distinct biological functions.

PMID- 8536620
TI  - Effects of extracellular nucleotides in the pituitary: adenosine triphosphate
      receptor-mediated intracellular responses in gonadotrope-derived alpha T3-1
      cells.
AB  - We have recently identified gonadotropes as target cells for ATP action via ATP
      receptors of the P2U subtype. The present studies have used gonadotrope-derived
      alpha T3-1 cells to examine the possible signaling mechanisms subserving ATP
      action in gonadotropes. Addition of ATP produced a biphasic intracellular Ca2+
      (Ca2+i) response: a transient spike followed by a small plateau. Removal of
      extracellular Ca2+ or depolarization with KCl abolished the plateau but had no
      effect on the spike. The plateau was also blocked by cadmium or nifedipine but
      not nickel. Pretreatment with GnRH or thapsigargin but not ryanodine inhibited
      the subsequent Ca2+i response to ATP. Pertussis toxin had no effect on ATP
      induced Ca2+i response, whereas the phospholipase C inhibitor U73122 reduced the
      response. These observations suggest that the Ca2+i response is mediated by a
      pertussis toxin-insensitive and phospholipase C-coupled G-protein and reflects
      Ca2+ release from the GnRH- and thapsigargin-sensitive Ca2+ pool followed by Ca2+
      influx through high voltage-gated Ca2+ channels. Activation of these ATP
      receptors had no apparent effects on the cAMP and cGMP signaling systems.
      Treatment with ATP-gamma S caused the translocation of protein kinase C (PKC)
      epsilon but not PKC zeta and PKC alpha to the particulate fraction. These data
      not only characterize the ATP receptor-mediated intracellular signaling in alpha
      T3-1 cells and render further evidence for a mediator role for nucleotides in
      gonadotrope function but also provide the first direct demonstration of PKC
      translocation by ATP receptors.

PMID- 8536621
TI  - Prouroguanylin and proguanylin: purification from colon, structure, and
      modulation of bioactivity by proteases.
AB  - Uroguanylin and guanylin are peptides isolated from urine and intestinal mucosa,
      which regulate cyclic GMP production in enterocytes by activating an apical
      membrane, receptor-guanylate cyclase. This study extended our previous findings,
      which showed that colonic mucosa of opossums contained uroguanylin and guanylin
      peptides, by purifying prouroguanylin and proguanylin from this tissue.
      Prouroguanylin and proguanylin coeluted from Sephadex G-75 gelfiltration columns
      with a similar molecular size between 6 and 12 kDa. Mass spectrometry indicated
      that proguanylin (approximately 8.7 kDa) had a 10% lower molecular mass than
      prouroguanylin (approximately 9.7 kDa). Isoelectric focusing separated
      prouroguanylin (pI approximately 4.5) from proguanylin (pI approximately 7.5). N
      terminal sequence analysis of reverse phrase-HPLC purified prohormones revealed
      13 amino acids in opossum proguanylin that shared 77-85% identity with human and
      rat proguanylin, but only 23% identity with opossum prouroguanylin. The N
      terminal 19 residues obtained for opossum prouroguanylin shared 32-42% identity
      with rat and human proguanylin. Prouroguanylin and proguanylin were both inactive
      and required pretreatment with proteases to elicit cyclic GMP responses in T84
      cells. V8 protease treatment of proguanylin liberated a bioactive, 16-amino acid
      form of guanylin. Chymotrypsin treatment activated prouroguanylin, but
      inactivated the bioactive peptide domain within proguanylin. In summary, colonic
      mucosa contains the bioactive peptide and inactive prohormone forms of
      uroguanylin and guanylin. Thus, after proteolytic processing of prouroguanylin
      and proguanylin, bioactive uroguanylin and guanylin could both function to
      regulate guanylate cyclase activity by autocrine and/or paracrine actions on
      enterocytes. Also, these peptide hormones are implicated in an intestinal-renal
      axis for the endocrine regulation of salt and water homeostasis.

PMID- 8536622
TI  - Differential effects of insulin and exercise on Rab4 distribution in rat skeletal
      muscle.
AB  - Insulin and exercise cause the translocation of GLUT4 from an intracellular
      location to the plasma membrane in skeletal muscle. The purpose of this study was
      to determine if Rab4, a small GTP binding protein that has been implicated in the
      insulin-stimulated translocation of GLUT4 in adipose cells, is involved in the
      regulation of transporter translocation in skeletal muscle. Male rats were
      injected with insulin (20 U i.p.) or exercised on a treadmill(1 h, 20 m/min, 10%
      grade). Rats were killed 30 min after insulin injection or immediately after
      exercise, and the hind limb muscles dissected. Plasma membrane and intracellular
      microsomal membrane fractions were prepared, and the distribution of GLUT4 and
      Rab4 was determined by immunoblotting. Both insulin and exercise caused GLUT4
      translocation as demonstrated by a decrease in microsomal membrane GLUT4 and an
      increase in plasma membrane GLUT4. In contrast, only insulin caused a decrease in
      Rab4 in the microsomal membrane. Rab4 was associated with GLUT4-containing
      vesicles isolated by immunoprecipitation. Rab4 was not detected in plasma
      membrane under any condition. These data demonstrate that insulin modulates the
      subcellular distribution of both GLUT4 and Rab4 in rats skeletal muscle,
      suggesting that Rab4 may play a role in the insulin-stimulated movement of GLUT4
      containing vesicles. Although both insulin and exercise increase skeletal muscle
      glucose uptake by the translocation of GLUT4, the regulation of translocation may
      occur by different mechanisms.

PMID- 8536623
TI  - Chronic estrogen treatment in male rats reveals mammosomatotropes and allows
      inhibition of prolactin secretion by somatostatin.
AB  - Previous in vivo studies demonstrated that estrogen treatment of male rats allows
      somatostatin (SRIF) to inhibit PRL release. The objective of this study was to
      determine whether chronic estrogen (E2) treatment of male rats can induce the
      conversion of somatotropes to mammosomatotropes. In situ hybridization and
      reverse hemolytic plaque assay were used to evaluate the effects of E2 treatment
      on GH and PRL messenger RNA (mRNA) content and hormone secretion in individual
      pituitary cells. Male rats were implanted for 2-6 weeks with placebo or estradiol
      containing pellets (5mg/90-day release). Pituitaries were removed and prepared
      for reverse haemolytic plaque assay to determine PRL and GH secretion. This was
      followed by in situ hybridization using 35S-labeled riboprobes for PRL and GH
      mRNA. Chronic E2 treatment increased both the percentage of pituitary cells that
      secreted PRL and the amount of PRL secreted per cell. Concomitantly, there was a
      decrease in both the percentage of GH-secreting cells and that amount of GH
      secreted per cell. In situ hybridization demonstrated that E2 treatment increased
      PRL mRNA while decreasing GH mRNA in single pituitary cells. Significantly, in
      control male rat pituitary cell cultures, no PRL-secreting cells were positive
      for GH mRNA. In contrast, after chronic E2 treatment, 10% of PRL-secreting cells
      contained GH mRNA. In the control pituitary cell cultures, SRIF had no effect on
      PRL release, but SRIF significantly inhibited PRL release from pituitary cell
      cultures prepared from E2-treated male rats. These studies demonstrate that the
      adult pituitary preserves plasticity and, under the appropriate steroid milieu,
      allows conversion of somatotropes to mammosomatotropes.

PMID- 8536624
TI  - Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth
      factor-binding protein-4 in mouse osteoblastic cells.
AB  - Thyroid hormone (T3) is a known regulator of the transcription rate of specific
      genes. By subtractive hybridization of T2-treated osteoblastic cells,
      differentially expressed messenger RNAs (mRNAs) were enriched in the form of
      double stranded complementary DNA (cDNA) fragments. Sequencing of a
      differentially expressed cDNA that detects a 2.6-kilobase mRNA in Northern blots
      revealed to homology in the EMBL-Genebank data bases. A mouse genomic library was
      screened, and the isolated genomic DNA was identified as part of the insulin-like
      growth factor-binding protein-4 (IGFBP-4) gene including the 3'-untranslated
      region to which the cloned cDNA fragment was mapped by sequencing. We observed an
      up-regulation of the 2.6-kilobase IGFBP-4 mRNA transcript in the presence of T3
      or retinoic acid. The induction of the IGFBP-4 transcript persisted up to 48 h.
      This response was inhibited by cycloheximide as well as actinomycin D. Long term
      induction studies revealed that the T3 effect is present during the complete
      culture period, with a constant rise in IGFBP-4 mRNA levels until 14 days. Under
      these culture conditions, the DNA content of MC3T3-E1 cells were significantly
      reduced by T3 and retinoic acid, indicating the repressive effect of both
      hormones on cell growth. Western immunoblots showed that the transcriptional
      induction is consequently transduced to increased IGFBP-4 levels in the
      conditioned medium of T3-treated cells. Our data show that thyroid hormone and
      retinoic acid stimulate transcription of IGFBP-4 mRNA in osteoblasts, resulting
      in increased IGFBP-4 secretion into the medium. IGFBP-4, a known inhibitor of
      cellular proliferation, might contribute to the antiproliferative effect of T3
      and retinoic acid on osteoblasts.

PMID- 8536625
TI  - Glucocorticoid-induced growth arrest of lung alveolar epithelial cells is
      associated with increased production of insulin-like growth factor binding
      protein-2.
AB  - Glucocorticoids have been shown to impair lung growth by altering development of
      the alveolar structure. To characterize the mechanisms involved in this process,
      we examined the effects of dexamethasone on proliferation of the stem cells of
      the alveolar epithelium, the type 2 cells. Treatment of type 2 cells with
      dexamethasone rapidly decreased DNA synthesis, and this effect was observed for
      concentrations less than 10(-8)M. Inhibition of cell proliferation by
      glucocorticoids was associated with a marked accumulation of insulin-like growth
      factor (IGF)-binding protein-2 (IGFBP-2) in the culture medium. Studies of the
      mechanisms involved in this accumulation indicated that it was associated with an
      enhanced production of IGFBP-2 and with a similar increase in the level of IGFBP
      2 messenger RNA expression without any changes in its stability, as evaluated by
      actinomycin D experiments. Furthermore, transfection studies using plasmids
      conveying expression of luciferase gene transcribed from the fragment of rat
      IBFBP-2 promoter extending from +12 bp relative to the start of transcription
      plus 1.4 kilobases of the 5'-flanking sequence showed a stimulation of luciferase
      activity in cells treated with dexamethasone that was similar to the increase in
      IGFBP-2 messenger RNA and protein. Study of the other components of the IGF
      system also revealed induction of IGF-II expression upon treatment with
      dexamethasone. Together with other previously reported results using various
      modulators of type 2 cell proliferation, the present study strongly suggests that
      IGFBP-2 is likely to play an important role in the control of alveolar epithelial
      cell proliferation.

PMID- 8536626
TI  - Tumor necrosis factor alpha stimulates insulin-like growth factor binding protein
      3 expression in cultured porcine Sertoli cells.
AB  - The present study was undertaken to analyze how a cytokine, the tumor necrosis
      factor alpha (TNF alpha), antagonizes the stimulatory action of insulin-like
      growth factor-I (IGF-I) on FSH receptor levels in testicular Sertoli cells. To
      achieve this purpose, we measured, in a model of primary culture of porcine
      Sertoli cells, the effects of TNF alpha on the IGF system that includes IGF-I and
      IGF-II, IGF binding proteins (IGFBPs), and IGF-I receptor (IGF-I R). We report
      that while TNF alpha had no consistent effect on the levels of IGF-I, IGF-II, or
      on IGF-I receptor (protein and messenger RNA (mRNA)], it stimulated IGFBP
      activity and particularly IGFBP-3. TNF alpha stimulated predominantly IGFBP-3
      (about 4-fold) both in terms of mRNA (a 2.6-kilobase transcript, measured by
      Northern blotting analysis), and protein (a doublet of 40-44 kDa, assessed by
      ligand blotting analysis). Such a stimulatory effect on IGFBP-3 was detected with
      a concentration as low as 0.1 ng/ml (5.5 pM) of TNF alpha. The stimulatory action
      of the cytokine was time dependent and was maximal at 7 h and 48 h, for IGFBP-3
      mRNA and protein, respectively. Such an increase in IGFBP-3 in TNF alpha-treated
      Sertoli cells results probably in a decrease in IGF-1 bioavailability for its
      receptors and thus in a decrease in IGF-I action. Indeed, addition of recombinant
      human IGFBP-3 (10 nM) suppressed completely the stimulatory addition of IGF-I (3
      nM) on FSH binding to cultured porcine Sertoli cells. Together, the present
      findings indicate that, in Sertoli cells, TNF alpha antagonizes IGF-I action
      through the modulation of IGFBPs and particularly through an increase in IGFBP-3.
      Because of the local production of both TNF alpha and components of the IGF
      system, such an interaction between the IGF system and the cytokine probably
      occurs in the context of physiological testicular somatic-germ cell interactions.

PMID- 8536627
TI  - Chronic administration of neuropeptide Y into the lateral ventricle inhibits both
      the pituitary-testicular axis and growth hormone and insulin-like growth factor I
      secretion in intact adult male rats.
AB  - Neuropeptide Y (NPY) is known to be involved in the central regulation of
      appetite, sexual behavior, and reproductive function. Whereas central
      administration of NPY strongly stimulates feeding in satiated animals, diet
      restriction or other unfavorable metabolic situations, such as diabetes, produce
      enhanced NPY gene expression and NPY release in the hypothalamus. Numerous
      studies have indicated that acute central administration of NPY results in
      various actions on LH secretion in the rat, either stimulatory or inhibitory. We
      recently demonstrated that chronic infusion of NPY into the lateral ventricle of
      adult intact female rats profoundly inhibited both the gonadotropic and
      somatotropic axes, with disruption of estrous cyclicity. Furthermore, we showed
      that central chronic infusion of NPY delayed sexual maturation in female rats. To
      analyze the effects of the same type of chronic NPY treatment on the pituitary
      testicular axis, 45-day-old Sprague-Dawley male rats were implanted with
      stainless steel cannulas in the right lateral ventricle. Ten days later, Alzet
      osmotic minipumps were filled with different NPY solutions, adjusted to deliver
      6, 18, or 36 micrograms/day, connected to the intracerebroventricular (icv)
      cannula, and sc implanted dorsally. The effects of these treatments were
      evaluated over 7 days. In one case, rats were castrated 5 days after initiation
      of NPY treatment, and the effect of castration was evaluated 2 days later.
      Chronic icv infusion of NPY produced the expected dose-related increases in food
      intake from 33.0 +/- 0.9 (basal) to 53.4 +/- 3.3 g/day (18 micrograms NPY/day)
      and body weight gain (5.7 +/- 0.7 to 10.5 +/- 1.2 d/day). As in female rats, this
      orexigenic action of NPY resulted in a significant dose-related decrease in
      pituitary weight, from 12.4 +/- 0.7 to 9.9 +/- 0.4 mg. The 7-day NPY infusion
      produced highly significant decreases in seminal vesicle weight (853 +/- 77 to
      230 +/- 31 mg) and testis weight (3.82 +/- 0.09 to 3.18 +/- 0.15 g; P = 0.003).
      Plasma levels of testosterone (231 +/- 71 to 48 +/- 13 ng/dl), LH (20.7 +/- 3.7
      to 9.1 +/- 1.2 ng/ml), and FSH (282 +/- 17 to 190 +/- 18 ng/ml) were markedly
      decreased at the 18 micrograms/day dosage, as also demonstrated for the 36
      micrograms/day dosage. None of these effects was observed if vehicle was infused
      into the lateral ventricle instead of the NPY solution. When bilateral
      orchidectomy was performed 5 days after initiation of the NPY infusion (18
      micrograms/day), the immediate LH and FSH rises usually seen after castration
      were seriously blunted.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8536628
TI  - Growth hormone-independent expression of insulin-like growth factor I messenger
      ribonucleic acid in extrahepatic tissues of the chicken.
AB  - The sex-linked dwarf (SLD) chicken, which lacks GH receptor (GHR), and its normal
      littermates provide a useful experimental system to investigate GH-dependent
      cellular responses. The GH dependence of insulin-like growth factor I (IGF-I)
      expression in tissues was examined in SLD and normal chickens of the Gifu 20
      strain. Four weeks after hatching, the most abundant expression of IGF-I
      messenger RNA (mRNA) was observed in liver of normal chickens, whereas no IGF
      mRNA expression was detected in that organ of dwarf chickens. On the contrary, in
      extrahepatic tissues such as spleen, lung, brain, kidney, heart, intestine,
      thymus, and muscle, IGF-I mRNA expression was equally observed in normal and GHR
      lacking dwarf chickens. In the testis, expression of IGF-I mRNA was enhanced by
      about 5-fold in dwarf chickens showing an expression level comparable to that in
      normal liver. On day 16 in the embryonic stage, IGF-I mRNA was expressed in
      muscle, brain, eye, heart, and lung in both normal and SLD chick embryos.
      However, no IGF-I mRNA expression was observed in liver or kidney of normal and
      dwarf chick embryos. These results suggest that in chicken, IGF-I mRNA is
      expressed in liver in a GH-dependent manner after hatching, whereas in other
      tissues, mRNA expression is independent of GH and GHR before and after hatching,
      except for testis, in which GH seems to inhibit IGF-I mRNA expression.

PMID- 8536629
TI  - Stimulation of mitogen-activated protein kinase by gonadotropin-releasing
      hormone: evidence for the involvement of protein kinase C.
AB  - GnRH regulates gonadotropin biosynthesis and secretion. Multiple intracellular
      signaling pathways are activated by GnRH, including phosphoinositol turnover,
      release of intracellular calcium and influx of extracellular calcium, and
      activation of protein kinase C (PKC), among others. In this study, we
      investigated whether GnRH stimulates mitogen-activated protein kinase (MAPKs),
      and whether this pathway plays a role in the transcriptional activation of the
      gonadotropin alpha-gene. In alpha T3-1 gonadotrope cells, treatment with GnRH
      caused 4- to 5-fold induction of MAPK activity. Stimulation of MAPK activity was
      detected within 5 min of GnRH treatment and persisted for 60 min. MAPK activation
      by GnRH was also seen in primary cultures of rat pituitary cells. Treatment with
      phorbol 12-myristate 13-acetate (TPA) caused 4- to 5-fold induction of MAPK
      activity in alpha T3-1 cells. Pretreatment with TPA, however, decreased both GnRH
      and TPA-induced MAPK activation, suggesting that PKC is involved in GnRH
      mediated activation of MAPK. Western blot analyses of PKC isoforms alpha and
      epsilon confirmed that they were depleted by chronic treatment with TPA, whereas
      MAPK protein levels were unaffected. Because transcriptional stimulation of the
      glycoprotein hormone alpha-gene by GnRH is also inhibited by PKC depletion,
      additional experiments were performed to explore a potential role for MAPK in
      alpha-gene expression. Cotransfection of a dominant negative inhibitors of MAPK
      isoforms (ERK1 and ERK2) suppressed basal expression of the alpha-promoter by
      60%, but had less effect on the extent of GnRH stimulation in alpha T3-1 cells.
      These experiments indicate that GnRH stimulates MAPK activity, probably through a
      pathway involving PKC. Although PKC depletion inhibits both MAPK- and GnRH
      stimulated alpha-gene transcription, pathways other than MAPK are also likely to
      be involved in mediating the transcriptional effects of GnRH.

PMID- 8536630
TI  - Physiological levels of calcitonin regulate the mouse osteoclast calcitonin
      receptor by a protein kinase Alpha-mediated mechanism.
AB  - We have reported that calcitonin (CT) treatment induced downregulation of the CT
      receptor (CTR) in mouse osteoclast-like cells (OCLs). Here, we studied the
      features of homologous down-regulation of the CTR in mature mouse OCLs. Treatment
      with salmon CT (sCT) and human CT (hCT) reduced [125I]sCT specific binding. The
      decreased binding after 24 h of CT treatment was associated with a decrease in
      the cell surface receptor concentration. The extent of CT-induced down-regulation
      in 24 h was dose-dependent, and the ED50 value was 3.6 +/- 4.1 (mean +/- SD; n =
      3) x 10(-13 M for sCT and 4.9 +/- 3.3 x 10(-11) M for hCT. These values were very
      similar to those for the CT inhibition of the bone-resorbing activity of OCLs.
      The data suggest that these two distinct actions of CT may be mediated by a
      common intracellular pathway. Treatment of OCLs with activators of protein kinase
      A (PKA) mimicked the effect of CT on CTR downregulation, whereas neither
      activation of protein kinase C nor elevation of intracellular Ca2+ did so.
      Attenuation of CT-induced CTR down-regulation by the competitive cAMP antagonist,
      RpcAMP, and high concentrations of H-7, but not by protein kinase C-specific
      inhibitors (sphingosine, staurosporine, and a lower concentration of H-7),
      suggested that the PKA pathway is primarily involved in homologous regulation of
      the CTR. The changes in CTR messenger RNA confirm the findings in binding studies
      and demonstrate that CT treatment of OCLs results in decreased CTR synthesis
      through the PKA pathway. The low concentrations of hCT that result in CTR
      regulation are very close to the physiological range, providing new insights into
      a dynamic relationship between circulating levels of CT and CTR expression in
      osteoclasts.

PMID- 8536631
TI  - Targeted expression of des(1-3) human insulin-like growth factor I in transgenic
      mice influences mammary gland development and IGF-binding protein expression.
AB  - To test the hypothesis that insulin-like growth factor I (IGF-I) regulates
      mammary gland development and lactation, the expression of both human (h) IGF-I
      and des(1-3)hIGF-I was targeted to the mammary gland in transgenic mice using a
      novel exon replacement strategy and the rat whey acidic protein (rWAP) gene
      regulatory sequences. Both transgenes expressed a 0.7-kilobase messenger RNA
      (mRNA). The abundance of WAP-IGE-I and WAP-DES mRNA on day 10 of lactation ranged
      from 0.2-1.0% and 0.2-13% of the endogenous mouse WAP mRNA, respectively. For WAP
      DES mice, transgene expression was greatest from midpregnancy throughout
      lactation. Western blot analysis showed the presence of correctly processed hIGF
      I in milk from these transgenic mice. This hIGF-I was capable of stimulating
      protein synthesis in cultured rat L6 myoblasts. Ligand blotting indicated changes
      in mammary gland secretion of IGFBP in response to WAP-DES expression.
      Histological analysis of mammary tissue from mice overexpressing des(1-3)hIGF-I
      showed incomplete mammary involution, ductile hypertrophy, and loss of secretory
      lobules associated with increased deposition of collagen. These changes are
      believed to occur through autocrine and paracrine effects of des(1-3)-hIGF-I on
      both epithelial and stromal cells.

PMID- 8536632
TI  - Immortalized murine osteoblasts derived from BMP 2-T-antigen expressing
      transgenic mice.
AB  - Osteoblast cell lines capable of undergoing bone formation in vitro would provide
      useful models for understanding gene expression during bone cell differentiation.
      To that end, transgenic mice were produced using a 2.9-kilobase bone
      morphogenetic protein 2 (BMP-2) promoter fragment, driving simian virus 40 T
      antigen as the transgene. The expression of simian virus 40 T antigen driven by
      the BMP-2 promoter immortalizes the cells. From the calvaria of the transgenic
      mouse, several osteoblastic cell lines were isolated and cloned. One clonal
      osteoblast cell line, called 2T3, has been characterized and shown to produce
      mineralized bone nodules. Recombinant human BMP-2 (rhBMP-2) accelerates the
      formation of these mineralized bone nodules. 2T3 cells express alkaline
      phosphatase, collagen type I, osteocalcin, and endogenous BMP-2 messenger RNA
      (mRNA) in a similar chronological order as normal freshly isolated fetal rat
      calvarial cells during early nodule formation and subsequent mineralization. The
      2T3 cells also exhibit extensive growth and multilayering during differentiation,
      as demonstrated by growth curves and transmission electron microscopy. As with
      freshly isolated fetal rat calvarial cells, 1,25-dihydroxyvitamin D3 inhibited
      alkaline phosphatase activity and alkaline phosphatase mRNA expression, but
      stimulated osteocalcin mRNA expression, but stimulated osteocalcin mRNA
      expression. rhBMP-2 also accelerated the expression of alkaline phosphatase
      activity and mRNA, osteocalcin mRNA, and BMP-2 mRNA in 2T3 cells along with the
      formation of larger and more mineralized bone nodules. The 2T3 cell exhibits
      autoregulation at the mRNA and transcriptional levels. The 2T3 osteoblast cell
      line offers a system for examining autoregulation of the BMP-2 gene and
      downstream gene expression during osteoblast differentiation. 2T3 cells are
      reclonable and maintain their differentiation capabilities.

PMID- 8536633
TI  - Estrogen and progesterone receptors, cell proliferation, and c-fos expression in
      the ovine uterus during early pregnancy.
AB  - To evaluate uterine growth during pregnancy and the potential roles of estrogen
      and progesterone in regulating uterine cell proliferation and c-fos expression,
      ewes were assigned randomly to slaughter on day 12 after estrus (nonpregnant,
      NP), and on days 12, 18, 24, or 30 after mating (pregnant, P) in Exp 1 (n = 7
      ewes/day) and on days 12 or 14 after estrus and on days 12, 14, 16, 18, 21, or 24
      after mating in Exp 2 (n = 3-6 ewes/day). In Exp 1, endometrial expression of c
      fos mRNA was evaluated, and labeling index was determined both in vitro
      (incorporation of 3H-thymidine) and in vivo (iv injection of bromodeoyxuridine
      [BrdU], a thymidine analog). Endometrial expression of the c-fos proto-oncogene
      was increased by approximately 10-fold on days 18, 24, and 30 P compared with day
      12 NP or P. Labeling index (proportion of cells incorporating 3H-thymidine or
      BrdU, which provides an index of the rate of cell proliferation) of endometrial
      caruncular and intercaruncular tissues was low for day 12 NP or P, increased on
      day 18 P, and remained elevated on days 24 P and 30 P. On day 18 P, labeling
      index also was greater for gravid than nongravid horns for both caruncular and
      intercaruncular tissues. In Exp 2, estrogen receptors (ER), progesterone
      receptors (PR), and proliferating (BrdU-positive) cells were immunolocalized. The
      percentage of cells exhibiting specific staining for ER, PR, and BrdU was
      quantified morphometrically for epithelial, stromal, and glandular tissues within
      luminal and deep regions, as well as for myometrial tissues. For luminal
      epithelium and glands, the rate of cell proliferation increased dramatically by
      day 18 P, even though ER and PR levels were low in these compartments.
      Conversely, the rate of cell proliferation remained low throughout early
      pregnancy in deep glands, deep stroma, and myometrium, in association with
      sustained or transient increases in ER and PR levels. For luminal stroma, the
      rate of cell proliferation increased by day 21 P even though ER levels were low
      and PR levels remained high. Thus, during early pregnancy, c-fos expression
      increased concomitantly with increased endometrial cell proliferation. In
      addition, during early pregnancy, ER and PR levels were inversely related to the
      rate of cell proliferation in most of the uterine tissue compartments except
      luminal stroma, which exhibited increased cell proliferation even though ER
      levels were low and PR levels remained high.

PMID- 8536634
TI  - Expression and localization of prolactin messenger ribonucleic acid in the human
      immune system.
AB  - Pituitary PRL is involved in immunoregulation. Also, a PRL-like molecule is
      secreted by peripheral blood mononuclear cells. In this study, we examined
      tissues of the human immune system to evaluate if the PRL gene is expressed and
      to determine the location and type of cells involved in its synthesis. To
      evaluate the expression of PRL messenger RNA (mRNA) in normal and abnormal human
      lymphoid tissues, we used RT-PCR to generate a specific 276-bp product from
      normal human thymus, spleen, tonsil, lymph node, and lymphoid tumors. Restriction
      enzyme digestion confirmed that this PCR product was expressed PRL. Furthermore,
      we developed a specific and sensitive nonisotopic in situ hybridization technique
      for PRL mRNA, and cells containing PRL mRNA were found in each tissue of the
      human immune system. Also, PRL mRNA was widely distributed throughout neoplastic
      tissue from a thymoma and lymphomas where mitogenic and anti-apoptotic properties
      of PRL could be involved in tumor progression. PRL mRNA was localized in
      lymphocytes, epithelial cells, and vascular endothelial cells. The presence of
      PRL mRNA in vascular endothelium cells suggests other roles for PRL in these
      tissues in addition to immunomodulation. In conclusion, the presence of PRL mRNA
      in human lymphoid tissue implies that locally synthesized PRL may play a critical
      role in immunocompetence by providing an important regulatory signal to the
      microenvironment of human lymphoid organs.

PMID- 8536635
TI  - Stimulatory effect of growth hormone on bone resorption and osteoclast
      differentiation.
AB  - Although the actions of GH on osteoblasts have been extensively investigated, its
      effects on osteoclasts remain unknown. In the present study, the effects of GH on
      bone resorption and osteoclast differentiation were examined in vitro. Bovine GH
      (bGH; 1-100 ng/ml) significantly stimulated bone resorption by preexistent
      osteoclasts in stromal cell-containing mouse bone cell cultures, whereas it did
      not affect the bone-resorbing activity of isolated rabbit osteoclasts. When bGH
      was added to unfractionated bone cells after degeneration of preexistent
      osteoclasts, it concentration dependently stimulated osteoclast-like cell
      formation. GH also enhanced 1,25-dihydroxyvitamin D3-induced osteoclast-like cell
      formation. Moreover, osteoclast-like cells newly formed from unfractionated bone
      cells in the presence of bGH possessed the ability to form pits on dentine
      slices. The conditioned medium from osteoblastic MC3T3-E1 cells or MC3T3-G2/PA-6
      stromal cells pretreated with bGH stimulated osteoclast-like cell formation from
      mouse hemopoietic blast cells supported by granulocyte-macrophage colony
      stimulating factor. On the other hand, the PCR products corresponding in size to
      the mouse GH receptor were detected in mouse hemopoietic blast cells as well as
      liver. GH concentration dependently stimulated osteoclast-like cell formation
      from these hemopoietic blast cells in the absence of stromal cells, and these
      osteoclast-like cells formed pits on dentine slices in the presence of MC3T3
      G2/PA-6 stromal cells. The present study indicated for the first time that GH
      stimulates osteoclastic bone resorption through both its direct and indirect
      actions on osteoclast differentiation and through its indirect activation of
      mature osteoclasts, possibly via stromal cells, including osteoblasts.

PMID- 8536636
TI  - Differential expression of peroxisome proliferator-activated receptors (PPARs):
      tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily that can be activated by various xenobiotics and
      natural fatty acids. These transcription factors primarily regulate genes
      involved in lipid metabolism and also play a role in adipocyte differentiation.
      We present the expression patterns of the PPAR subtypes in the adult rat,
      determined by in situ hybridization using specific probes for PPAR-alpha, -beta
      and -gamma, and by immunohistochemistry using a polyclonal antibody that
      recognizes the three rat PPAR subtypes. In numerous cell types from either
      ectodermal, mesodermal, or endodermal origin, PPARs are coexpressed, with
      relative levels varying between them from one cell type to the other. PPAR-alpha
      is highly expressed in hepatocytes, cardiomyocytes, enterocytes, and the proximal
      tubule cells of kidney. PPAR-beta is expressed ubiquitously and often at higher
      levels than PPAR-alpha and -gamma. PPAR-gamma is expressed predominantly in
      adipose tissue and the immune system. Our results suggest new potential
      directions to investigate the functions of the different PPAR subtypes.

PMID- 8536637
TI  - Proliferation of microvascular endothelial cells in the primate corpus luteum
      during the menstrual cycle and simulated early pregnancy.
AB  - The objective of this study was to evaluate endothelial vs. steroidogenic cell
      proliferation throughout the lifespan of the primate corpus luteum during the
      menstrual cycle and simulated early pregnancy (CG treatment). Tissues were
      collected from rhesus monkeys (Macaca mulatta; n = 3/day) on days 3-4, 7, 10, 12,
      and 14 of the of the luteal phase and at menses during spontaneous menstrual
      cycles and after 1, 3, 6, or 9 days of hCG treatment beginning on day 9 of the
      luteal phase. Corpora lutea were snap-frozen in mounting medium for
      immunocytochemical and histochemical evaluation. The labeling index (percentage
      of positive to total nuclei) for Ki-67 antigen, a cell proliferation marker, was
      determined in conjunction with cell-specific markers. Immunolocalization of
      platelet/endothelial cell adhesion molecule-1 and von Willebrand factor in
      addition to histochemical staining for the Ulex europaeus agglutinin-1 (i.e.
      lectin)-binding site were used to identify endothelial cells. Histochemical
      detection of 3 beta-hydroxysteroid dehydrogenase activity was used to identify
      steroidogenic cells. Progesterone secretion was high on days 3-10 of the luteal
      phase and then declined progressively (P < 0.05) on days 12 and 14 and at menses;
      luteal weight followed a similar pattern, declining 2 days (i.e. day 14) after
      progesterone secretion. In contrast, after hCG treatment, luteal progesterone
      production increased (P < 0.05) 3-fold, and luteal weight was maintained. The
      cell proliferation index was greatest (44.5 +/- 1.9%) on days 3-4 of the luteal
      phase and remained high on days 7 and 10 (34.6 +/- 0.3% and 27.1 +/- 3.4%), but
      this was followed by a sharp decline on day 12 (9.6 +/- 2.3%), which was
      sustained on day 14 and at menses. After 1 day of hCG treatment, cell
      proliferation was less than that observed on the equivalent day of the luteal
      phase (day 10), but thereafter, it was similar on days 3, 6, and 9 of simulated
      early pregnancy to those in the late luteal phase of the menstrual cycle (i.e.
      day 12 to menses). Dual label immunocytochemistry indicated that more than 85% of
      cells staining positively for the Ki-67 antigen costained for
      platelet/endothelial cell adhesion molecule-1. No cells staining positively for
      both 3 beta-hydroxysteroid dehydrogenase activity and the Ki-67 antigen were
      noted. Thus, the level of cell proliferation within the primate corpus luteum
      varies during the luteal lifespan in the menstrual cycle, and endothelial cells
      comprised the vast majority of proliferative cells, whereas steroidogenically
      active cells were not proliferating. Further, the elevated progesterone secretion
      and sustained luteal weight that occurred during CG exposure simulating early
      pregnancy were not associated with an increase or maintenance of cellular
      proliferation.

PMID- 8536638
TI  - Targeted expression of the ret/PTC1 oncogene induces papillary thyroid
      carcinomas.
AB  - The ret/PTC oncogene, a rearranged form of the ret proto-oncogene, has been found
      to be restricted to human papillary thyroid carcinomas. This report shows that
      transgenic mice with thyroid-targeted expression of the ret/PTC1 oncogene
      developed thyroid carcinomas with considerable similarities to human papillary
      thyroid carcinomas, particularly in the nuclear cytologic features and the
      presence of local invasion. Our findings indicate that ret/PTC2 is not only a
      biomarker associated with papillary thyroid carcinomas, but is also the only
      proven specific genetic event leading to the development of papillary thyroid
      carcinoma.

PMID- 8536639
TI  - Glucocorticoid stimulation of pro-ANF mRNA expression of adult rat hypothalamic
      neurons in culture: a cAMP-dependent effect.
AB  - We describe here long term primary cultures of adult rat hypothalamic cells, a
      novel system which we have exploited to examine the effect of glucocorticoids on
      adult ANF neurons in vitro. ANF neurons with and without neurite outgrowths were
      identified by immunocytochemistry and by in situ hybridization studies, in which
      pro-ANF mRNA signals were localised in cultured cells. Dexamethasone (DM)
      augmented the abundance of pro-ANF mRNA signals in a dose-related manner with
      ED50 of 5 x 10(-12)M and Emax of 10(-10)M. This stimulation effect was mimicked
      by corticosterone but not by deoxycorticosterone. Similarly, activation of the
      adenylyl cyclase-cAMP system with forskolin, 8-brom-cAMP or 3-isobutyl-1
      methylxanthine (IBMX), also markedly elevated the level of pro-ANF mRNA
      abundance. Interestingly, whereas forskolin-induced stimulation was reversed by
      Rp-cAMP, a cAMP antagonist, the augmentation induced by DM alone or by DM and
      forskolin together, was similarly suppressed by the chemical. We therefore
      conclude that (i) adult ANF neurons are capable of regenerating neurite
      outgrowths in vitro, (ii) cAMP dependent pathways play a fundamental role in
      regulating the expression of pro-ANF mRNA, and (iii) the stimulatory effect of
      glucocorticoids is indirect and mediated, at least in part, through modulating
      the activity of cAMP dependent pathways.

PMID- 8536640
TI  - C-type natriuretic peptide as a possible local modulator of aldosterone secretion
      in bovine adrenal zona glomerulosa.
AB  - Although atrial and brain natriuretic peptides are well known to be involved in
      the regulation of cardiovascular and endocrine functions as circulating hormones,
      the roles of the C-type natriuretic peptide (CNP) remain unknown. We examined the
      effects of CNP on the secretion of aldosterone and cyclic nucleotides from bovine
      adrenal zona glomerulosa cells in culture. CNP produced a dose-dependent increase
      in the basal secretion of cGMP, with an EC50 of 3.8 x 10(-10)M. CNP significantly
      inhibited the ACTH-induced increase in aldosterone and cAMP in a dose-related
      manner, with an IC50 of 3.6 x 10(-10)M. Although ACTH itself did not increase
      cGMP secretion, the addition of CNP elicited a significant increase in cGMP
      secretion. The effects of CNP on the basal secretion of cGMP and the ACTH-induced
      secretion of aldosterone were significantly reversed by a nonpeptide natriuretic
      peptide receptor antagonist, HS-142-1. CNP immunoreactivity was localized in the
      zona glomerulosa by immunohistochemical staining. In addition, expression of CNP
      messenger RNA and natriuretic peptide B receptor messenger RNA was demonstrated
      by RT-PCR in the zona glomerulosa tissue and cells in culture. These findings
      suggest that CNP is a local factor regulating ACTH-induced aldosterone secretion
      through a guanylyl cyclase-cGMP pathway.

PMID- 8536641
TI  - The responsiveness of tuberoinfundibular dopaminergic neurons to prolactin
      feedback is diminished between early lactation and midlactation in the rat.
AB  - Lactation is a state of hyperprolactinemia resulting in part from suppressed
      tuberoinfundibular dopaminergic (TIDA) neuronal activity. The suckling stimulus
      contributes to this suppression despite the fact that the TIDA neurons are a
      potential site for PRL feedback to increase neuronal activity. This study
      examined the influence of PRL feedback and the suckling stimulus on tyrosine
      hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, during early
      and midlactation. On day 3 or 10 of lactation, rats were injected
      intracerebroventricularly with medium (control) or MMQ cells (200,000 cells), a
      PRL-secreting cell line. On day 6 of lactation, TH activity in the stalk-median
      eminence was increased 2- or 1.4-fold by MMQ cells or prior treatment with ovine
      PRL (oPRL; 4 mg/kg, sc), respectively. Removal of pups for 24 h increased TH
      activity 70% above levels in pup-exposed rats, and MMQ cells or oPRL caused an
      additional 60% increase. TH messenger RNA (mRNA) levels in the arcuate nucleus
      were increased 3-fold after removing the pups, but MMQ cells did not alter mRNA
      levels in either pup-exposed or pup-deprived dams. In contrast to early
      lactation, MMQ cells did not alter TH activity or mRNA levels in the pup-exposed
      dams on day 13 and only marginally increased enzyme activity in pup-derived dams.
      Circulating PRL levels were markedly reduced after removing pups. MMQ cells
      suppressed circulating PRL levels in both groups of dams on day 6 and in pup
      deprived dams on day 13, but had no effect in pup-exposed dams at this time. In a
      second experiment, pup-exposed dams were injected with bromocriptine, a dopamine
      agonist, and killed after 4 or 12 h on day 5 or after 12 h on day 12. In some
      rats, PRL was replaced by injecting oPRL simultaneously with and 8 h after
      bromocriptine treatment. On day 5 of lactation, bromocriptine reduced and oPRL
      restored TH activity, whereas on day 12, oPRL was not able to reverse the effect
      of bromocriptine. These data indicate that the suckling stimulus suppresses TH
      activity and gene expression in the TIDA neurons in pup-exposed dams. The high
      endogenous PRL levels associated with the suckling stimulus may activate TH
      activity in TIDA neurons during early lactation. However, the responsiveness of
      the TIDA neurons to PRL feedback is attenuated by day 13 of lactation.

PMID- 8536642
TI  - Acute nuclear actions of growth hormone (GH): cycloheximide inhibits inducible
      activator protein-1 activity, but does not block GH-regulated signal transducer
      and activator of transcription activation or gene expression.
AB  - The mechanisms by which GH regulates gene expression to stimulate somatic growth
      and alter intermediary metabolism are unknown. We have shown previously that in
      vivo GH administration rapidly modifies the tyrosine phosphorylation of multiple
      hepatic nuclear proteins, including the inducible transcription factors, Stat1,
      Stat3, and (in this report) Stat5, and have found that hormone treatment also
      rapidly alters gene transcription in the liver. In this study, we have used the
      protein synthesis inhibitor, cycloheximide (CHX), to investigate which of the
      acute actions of GH are primary hormonal responses and which require concurrent
      protein synthesis. We found that many of the early changes in nuclear protein
      tyrosine phosphorylation and in nuclear protein-DNA binding after GH are not
      blunted by CHX. The activation of insulin-like growth factor I and Spi 2.1 gene
      expression and the inhibition of albumin transcription also are not blocked by
      CHX, suggesting that these effects are primary consequences of GH-activated
      signal transduction pathways. By contrast, CHX completely inhibits the induction
      of activator protein-1 DNA-binding activity by GH, indicating that this action is
      secondary to the stimulation of Fos and/or Jun protein biosynthesis. Our results
      support the idea that multiple primary and secondary signaling pathways
      contribute to the pleiotropic effects of GH on gene expression and provide a
      framework for delineating the mechanisms controlling the acute actions of GH.

PMID- 8536643
TI  - Corticotropin-releasing factor (CRF) and glucocorticoids modulate the expression
      of type 1 CRF receptor messenger ribonucleic acid in rat anterior pituitary cell
      cultures.
AB  - Previous studies involving radioreceptor and functional assays have shown that
      CRF and glucocorticoids are able to modulate CRF receptors of the brain and
      anterior pituitary. In this study, we analyzed the effects of CRF, vasopressin
      (AVP), dexamethasone (DEX), and corticosterone on the regulation of CRF receptor
      (CRF-R1) messenger RNA (mRNA) levels in cultured rat anterior pituitary cells.
      CRF decreased CRF-R1 mRNA levels in a time- and concentration-dependent manner.
      In the presence of 10 nM CRF, CRF-R1 mRNA levels decreased within 1 h (to 65 +/-
      3% of the control value; P < 0.01) with a maximal effect after 3 h (to 28 +/- 1%
      of the control value; P < 0.001). The concentration dependence of the inhibitory
      effect of CRF at 3 h correlated with that required for ACTH secretion (half
      maximal at approximately 0.03 nM). Treatment with a maximal (100 nM) dose of AVP
      or a submaximal (0.1 nM) dose of CRF for 3 h reduced CRF-R1 mRNA levels to 66 +/-
      3% and 53 +/- 6% of the control value, respectively. In the presence of both AVP
      and CRF, CRF-R1 mRNA levels were 32 +/- 3% of the control value. The incubation
      of cells for 3 h with 10 microM forskolin to activate adenylate cyclase or with
      20 nM 12-0-tetradecanoylphorbol-13-acetate to activate protein kinase C resulted
      in a decrease in receptor mRNA levels to 40 +/- 9% (P < 0.01) and 28 +/- 8% (P <
      0.001) of the control value, respectively, suggesting that the effects of CRF and
      AVP may be mediated by these pathways. DEX (20 nM) also caused a dose- and time
      dependent decrease in mRNA levels. Maximal inhibition was observed after 3 h (to
      31 +/- 6% of the control value; P < 0.001), with a partial recovery of mRNA
      levels at 24 or 48 h. Corticosterone similarly inhibited the accumulation of CRF
      R1 mRNA in a dose- and time-dependent manner, but, in contrast to DEX, CRF-R1
      mRNA levels returned almost to control levels after 24 h. These results indicate
      that the ability of CRF, AVP, and glucocorticoids to modulate the responses of
      corticotropes to CRF may be due in part to the actions of these agents on CRF-R1
      mRNA accumulation.

PMID- 8536644
TI  - Cloning and characterization of the human corticotropin-releasing factor-2
      receptor complementary deoxyribonucleic acid.
AB  - Two CRF receptor subtypes (CRF1 and CRF2 receptors) with distinct brain
      localizations and pharmacological profiles have recently been cloned and
      characterized. For the CRF2 receptor subtype, at least 2 splice forms with
      different 5'-coding sequences (CRF2 alpha and CRF2 beta) have been identified in
      rat. In this article, we report the genomic structure and the corresponding
      complementary DNA (cDNA) sequence of the human CRF2 receptor. The gene coding for
      human CRF2 receptor consists of at least 12 exons and spans approximately 30
      kilobases. The cDNA sequence in the protein-coding region is 94% identical to
      that of the reported rat CRF2 alpha receptor. At present, there is no evidence
      for the existence of a CRF2 beta receptor homolog in humans. The encoded receptor
      is 411 amino acids in length and is 70% identical to the human CRF1 receptor,
      with least sequence homology in the N-terminal extracellular domain (47%
      identical). Cells transfected with the full-length human CRF2 receptor cDNA
      responded to rat/human CRF and sauvagine by increasing the intracellular cAMP
      level, with EC50 values of approximately 20 and 1 nM, respectively. The CRF- and
      sauvagine-induced accumulation of intracellular cAMP could be competitively
      inhibited by the CRF receptor antagonist D-Phe-CRF. This pharmacological profile
      was comparable to that of the rat CRF2 alpha receptor. The relative abundance of
      the CRF2 receptor messenger RNA appears to be lower in humans than in rats for
      the tissues studied thus far.

PMID- 8536645
TI  - Disinhibition from opioid influence augments hypothalamic neuropeptide Y (NPY)
      gene expression and pituitary luteinizing hormone release: effects of NPY
      messenger ribonucleic acid antisense oligodeoxynucleotides.
AB  - It is well known that hypothalamic endogenous opioid peptides (EOP) exert an
      inhibitory influence on LH release, and that a restraint on this inhibitory tone
      triggers preovulatory LHRH and LH hypersecretion. Recent evidence suggests that
      hypothalamic neuropeptide Y (NPY) is an important component of the neural
      circuitry that participates in induction of the LH surge. We have reported
      previously that blockade of EOP influence by the opioid receptor antagonist,
      naloxone (NAL), stimulated NPY accumulation in the median eminence (ME) in
      association with increased LH release in estradiol-17 beta-primed ovariectomized
      rats. To evaluate whether a restraint on the EOP system will result in an
      increase in NPY synthesis, the effects of NAL infusion on preproNPY messenger RNA
      (mRNA) levels in the medial basal hypothalamus were studied by solution
      hybridization/RNase protection assay and by in situ hybridization. NAL (2 mg/0.6
      ml.h) or saline (SAL, 0.6 ml/h) was infused for 3 h (1100-1400 h) via an
      intrajugular cannula in estradiol-17 beta-primed ovariectomized rats. In accord
      with previous studies, NAL infusion significantly increased plasma LH levels at
      1400 h. concomitant with this activation of LH release, NPY gene expression was
      also augmented. As compared with initial control levels at 1100 h, preproNPY mRNA
      levels in the medial basal hypothalamus increased at 1400 h in SAL (106%)- and
      NAL (202%)-infused rats, and at this time, preproNPY mRNA levels were
      significantly higher in NAL-infused rats than in SAL-infused rats. In situ
      hybridization studies showed that NAL infusion significantly increased the
      preproNPY mRNA signal at 1400 h mainly in the rostral and middle regions of the
      arcuate nucleus (ARC) as compared with that seen at 1100 and 1400 h in SAL
      infused rats. To examine further the relationship between the NAL-induced
      increase in LH release and increase in NPY gene expression, the effects of NPY
      mRNA antisense oligonucleotides (oligos) on NPY levels in the ME-ARC and on
      plasma LH levels were studied in NAL-infused rats. In NAL-infused rats,
      intracerebroventricular administration of a NPY antisense oligo (25
      micrograms/rat) at 1000, 1200, and 1300 h decreased NPY levels in the ME-ARC and
      blocked the increase in plasma LH levels at 1500 h, whereas control missense
      oligos had no effect. Collectively, these results show that a decrease in opioid
      influence rapidly augments NPY gene expression in a subpopulation of neurons in
      the ARC, and support the hypothesis that a disinhibition from opioid influence
      acutely promotes NPY synthesis and release, which is necessary for phasic LH
      discharge in rats.

PMID- 8536646
TI  - Mechanism of the inhibitory action of RU486 on the secondary follicle-stimulating
      hormone surge.
AB  - Recent evidence utilizing RU486 has implicated progesterone (P) and
      glucocorticoids, in addition to a drop in serum inhibin, in the development of
      the secondary FSH surge on the morning of estrus. To assess the role of these
      steroids, we treated proestrous female rats with the
      antiprogestin/antiglucocorticoid RU486 (6 mg/kg sc) at 1230 h, and with
      dexamethasone (dex; 8.4 or 16.2 mg/kg sc), or with the steroid biosynthesis
      inhibitor aminoglutethimide (AG; 150 mg/kg ip) at 1030 h, alone or in combination
      with RU486. The effects of these treatments on uterine ballooning and
      intraluminal fluid content (an index of P action), ovulation, and serum levels of
      P, corticosterone (B), FSH, LH, and inhibin-alpha at 1830 h proestrus and 0900 h
      estrus were examined. In accord with previous work from our laboratory, RU 486
      caused uterine intraluminal fluid retention on the morning of estrus and
      significantly suppressed the preovulatory surges of both FSH and LH, and the
      secondary surge of FSH without affecting the fall in inhibin-alpha. Treatment
      with dex alone raised serum FSH at both 1830 h proestrus and 0900 h estrus,
      coincident with suppression of serum inhibin-alpha. When administered in
      combination with RU486, dex partially reversed the increased uterine intraluminal
      fluid retention at 0900 h estrus, but did not modify the inhibitory effect of
      RU486 on the primary gonadotropin surges or the secondary surge of FSH. AG alone
      significantly suppressed serum P, B, and gonadotropins (LH to a greater extent
      than FSH) at 1830 h proestrus and blocked ovulation and uterine intraluminal
      fluid release at 0900 h estrus; it did not, however, suppress the secondary FSH
      surge or prevent the fall in serum inhibin-alpha. When administered 2 h before
      RU486, AG did not prevent the RU486-induced inhibition of the primary
      gonadotropin surges or the secondary FSH surge. We conclude from these results
      that development of the secondary FSH surge does not require P or glucocorticoid
      action and that RU486 suppression of the secondary FSH surge does not involve
      blockade of binding of these steroids to their receptors. Our data are compatible
      with ligand-independent activation of the P receptor, susceptible to blockade by
      RU486, as the mechanism underlying the enhanced secretion of FSH from the
      gonadotrope on the morning of estrus.

PMID- 8536647
TI  - Human growth hormone fragments 1-43 and 44-191: in vitro somatogenic activity and
      receptor binding characteristics in human and nonprimate systems.
AB  - Human GH (hGH) fragments 1-43 and 44-191 have potent in vivo effects on glucose
      homeostasis in rodents but cannot stimulate body growth. To assess the in vitro
      bioactivity of these hGH fragments we tested their activity against GH-responsive
      FDC-P1 cell lines expressing full-length human (h), mouse (m), or rabbit (r) GH
      receptors (GHR). Binding specificity and affinity was tested using GHR-containing
      membrane preparations from three species and recombinant hGH binding protein
      (hGHBP). Recombinant hGH 1-43 and recombinant 44-191 stimulated proliferation of
      FDC-P1-hGHR cells with half-maximal effect at approximately 2000 and 100 nM,
      respectively, whereas intact hGH stimulates proliferation of FDC-P1-hGHR cells
      with ED50 of 0.02-0.03 nM. However, these fragments had minimal effect on cells
      expressing mGHR or rGHR. Although 44-191 did not stimulate proliferation of FDC
      P1-rGHR cells, when added to these cells in the presence of 0.23 nM hGH, it
      antagonized hGH action in a dose-dependent manner (ED50 at 230 nM). Binding of
      these GH fragments was compared using membrane preparations from rabbit liver,
      rabbit and mouse adipose tissue, and recombinant hGHBP. Binding competition
      curves were consistent, with 44-191 having at least a 10-fold lower affinity for
      rabbit liver GHR and rabbit adipose GHR than bovine GH and a 61-fold lower
      affinity for hGHBP than hGH. Binding of hGH 1-43 could not be demonstrated to
      GHRs in rabbit liver microsomes, adipose microsomes, or to hGHBP. HGH 1-43 did
      not compete for insulin binding sites in adipose microsomes. In conclusion, hGH
      44-191 binds with low affinity to the GHR and at supraphysiologic levels
      stimulates proliferation of FDC-P1-hGHR cells. At high doses, 44-191 can also
      antagonize GH action in FDC-P1-rGHR cells, presumably by blocking receptor
      dimerization. Binding of 1-43 to GHR could not be detected, and the basis for its
      weak in vitro mitogenic effect remains to be elucidated. The low affinity of the
      fragments for cloned GHRs and low biopotency in these systems suggests that the
      metabolic actions of these fragments are unlikely to be mediated by the cloned
      GHR. This raises the possibility of a separate receptor mediating metabolic
      effects of these fragments.

PMID- 8536648
TI  - Ras inhibits thyroglobulin expression but not cyclic adenosine monophosphate
      mediated signaling in Wistar rat thyrocytes.
AB  - We previously reported that microinjection of purified Ras protein stimulated DNA
      synthesis in quiescent Wistar rat thyrocytes and that TSH (TSH)-stimulated DNA
      synthesis was Ras-dependent. In contrast to these results, microinjection of
      cellular or oncogenic Ras significantly reduced TSH-stimulated thyroglobulin (Tg)
      expression, a marker of thyrocyte differentiation. Microinjection of a dominant
      inhibitory Ras mutant had no effect on TSH-stimulated Tg expression. As the Tg
      promoter is cAMP-responsive and Ras was previously reported to interfere with
      entry of catalytic (C) subunit of the cAMP-dependent protein kinase into the
      nucleus, experiments were performed to assess the effects of Ras on cAMP-mediated
      signaling. Microinjection of either cellular or oncogenic Ras had no effect on
      TSH-stimulated entry of C subunit into the nucleus. Consistent with these data,
      Ras did not reduce TSH-stimulated cAMP response element binding protein
      phosphorylation, or cAMP response element-regulated gene expression. These
      results demonstrate that Ras exerts differential effects on TSH signaling; Ras
      increases TSH-stimulated DNA synthesis and decreases TSH-induced Tg expression.
      Moreover, the mechanism through which Ras induces Tg expression lies distal to
      entry of C subunit into the nucleus, cAMP response element binding protein
      phosphorylation, and cAMP response element-regulated gene expression.

PMID- 8536649
TI  - Anti-inflammatory diet in rheumatic diseases.

PMID- 8536650
TI  - Who complied with COMA 1984 dietary fat recommendations among a nationally
      representative sample of British adults in 1986-7 and what did they eat?

PMID- 8536651
TI  - Repeated 24-h recalls with young schoolchildren. A feasible alternative to
      dietary history from parents?

PMID- 8536652
TI  - High socioeconomic class preschool children from Jakarta, Indonesia are taller
      and heavier than NCHS reference population.

PMID- 8536653
TI  - A universal growth reference or fool's gold?

PMID- 8536654
TI  - Effects of different soluble: insoluble fibre ratios at breakfast on 24-h pattern
      of dietary intake and satiety.

PMID- 8536655
TI  - Contaminants and nutrients in total diets in Spain.

PMID- 8536656
TI  - Instant coffee and cholesterol: a randomised controlled trial.

PMID- 8536657
TI  - Racing horses, nitroglycerin and exercise induced pulmonary haemorrhage (EIPH).

PMID- 8536658
TI  - Imaging infection and inflammation in veterinary practice.

PMID- 8536659
TI  - Practical implications of pharmacokinetic and pharmacodynamic (PK/PD) modelling
      of drug dose regimens.

PMID- 8536660
TI  - Comparison of the anti-inflammatory actions of flunixin and ketoprofen in horses
      applying PK/PD modelling.
AB  - A comparative study in horses of the pharmacokinetics (PK) and pharmacodynamics
      (PD) of 2 extensively used nonsteroidal anti-inflammatory drugs (NSAIDs),
      flunixin (FXN) and ketoprofen (KTP), was carried out applying PK/PD modelling. To
      evaluate the anti-inflammatory properties of these drugs a model of acute
      inflammation, comprising surgically implanted subcutaneous tissue cages
      stimulated by intracaveal injection of carrageenan, was used. FXN elimination
      half-life (T1/2 beta) in plasma was 3.37 +/- 1.09 h. However, in exudate a much
      longer T1/2 beta was obtained (15.99 +/- 3.80 h). Apparent volume of distribution
      (Vdarea) for FXN was 0.317 +/- 0.126 l/kg and body clearance (ClB) was 0.058 +/-
      0.004 l/kg/h. KTP displayed enantioselective pharmacokinetics, the S(+)
      enantiomer being predominant in plasma, exudate and transudate. T1/2 beta values
      for R(-) and S(+)KTP were, respectively, 1.09 +/- 0.19 h and 1.51 +/- 0.45 h
      (plasma) and 19.73 +/- 2.72 h and 22.64 +/- 4.34 h (exudate), respectively. R(
      )KTP was cleared more rapidly than the S(+) enantiomer. ClB values were 0.277 +/-
      0.035 l/kg/h and 0.202 +/- 0.022 l/kg/h, respectively. FXN and KTP
      pharmacodynamics was evaluated by determining their inhibitory effects on serum
      thromboxane (Tx)B2, exudate prostaglandin (PG)E2, leukotriene (LT)B4 and beta
      glucuronidase (beta-glu) and intradermal bradykinin-induced swelling. Both drugs
      produced marked inhibition of serum TxB2 synthesis for up to 24 h, with no
      significant differences between the drugs. FXN was a more potent inhibitor of
      exudate PGE2, the EC50 for FXN being lower (P < 0.01) than that for KTP (0.019 +/
      0.010 microgram/ml and 0.057 +/- 0.009 microgram/ml, respectively). Neither drug
      had any effect on exudate LTB4 concentration. Differences between the 2 drugs
      were observed for the inhibition of beta-glu, the Emax for KTP being higher (P <
      0.01) than for FXN. However, no differences were observed in other PD parameters.
      Both FXN and KTP inhibited bradykinin-induced swelling. Differences between the
      drugs were obtained for Emax, which was greater for FXN (P < 0.01) than for KTP.
      Equilibration half-life (T1/2Ke0) also differed, being much longer (P < 0.01) for
      FXN than for KTP. PK/PD modelling proved to be a useful and novel analytical
      technique for studying the pharmacodynamics of NSAIDs, with the advantage over
      classical in vitro methods that it provides data in the whole animal. By
      quantifying action-concentration interrelationships through PK-PD modelling, it
      is possible to shed light on molecular mechanisms of drug action, and establish
      probable differences in mechanisms of action between structurally similar
      drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8536661
TI  - Ventilatory and timing parameters in normal horses at rest up to age one year.
AB  - The purpose of the study was to document the developmental changes in the
      ventilatory and timing parameters associated with quiet breathing at rest in
      awake, standing horses during the first year post partum. Tidal volume (VT),
      breathing frequency, airflow, mechanical timing intervals and minute ventilation
      (VE) were measured serially in foals age 24 h-1 year. In the growing foal, VE
      increased due to a progressive rise in VT, in spite of a pronounced decrease in
      respiratory frequency. When normalised to body weight (bwt), VE/kg declined with
      maturation in a curvilinear fashion, from mean +/- s.d. 848 +/- 231 ml/min/kg in
      the 24 h-old foal, to 155 +/- 15 ml/kg/min in the 1-year-old foal. Tidal volume
      normalised to bwt remained relatively constant during the study period, with the
      exception that at age 3 weeks and from 2-6 months, VT/kg was significantly lower
      than the value recorded at age 1 week. The decrease in frequency resulted from
      prolongation of both inspiratory (TI) and expiratory (TE) time but there was a
      disproportionately larger increase in TE compared to TI, which resulted in a
      significantly lower ratio of TI/TE in older foals. The allometric equation
      relating VT to bwt suggested that lung growth in the horse is dysanaptic, with
      increases in overall body size exceeding lung growth in the maturing foal during
      the first year post partum.

PMID- 8536662
TI  - Changes in breathing pattern in the normal horse at rest up to age one year.
AB  - Changes in pattern of airflow, sequence of respiratory muscle activation and
      generated pressures were measured serially in a group of foals during the first
      year post partum, in order to describe the maturation of the equine breathing
      pattern. In neonatal foals, inspiration and expiration were both primarily active
      and airflow pattern was essentially monophasic. By age 1 year, foals displayed
      essentially the same breathing pattern previously described in adult horses,
      utilising a combination of active and passive inspiration and expiration to
      breathe around, rather than from, the relaxation volume of the respiratory system
      (Vrx). A strong temporal relationship during growth was found between the timing
      of changes observed in airflow pattern and in the neuromuscular strategy of
      breathing. The transition to the adult breathing pattern appeared to involve a
      time delay in activation of both inspiratory and expiratory muscle groups,
      establishing a passive and active component to both inspiration and expiration.
      Throughout the study period, concurrent with the increase in delay of abdominal
      muscle activation, the expiratory flow pattern became progressively more biphasic
      in appearance. The time of appearance of a consistent biphasic inspiratory flow
      pattern was considerably later, at approximately age 1 year and coincided with
      the appearance of a delay in inspiratory muscle activation. From our results, we
      conclude that the transition from the neonatal to the adult breathing strategy in
      the horse appears not to be induced by the time course of chest wall stiffening
      during maturation. While changes in relative body proportions and size of
      abdominal contents during growth may influence the transition in breathing, our
      results also indicate that respiratory control mechanisms play an essential role
      in the expression of the polyphasic breathing pattern.

PMID- 8536664
TI  - Biokinematic effects of collection on the trotting gaits in the elite dressage
      horse.
AB  - Trot in hand, working trot, collected trot, passage and piaffe of 6 Grand Prix
      dressage horses were recorded by high speed film (250 frames/s). Angular patterns
      and hoof trajectories of the left fore- and hindlimbs were analysed and presented
      as mean and standard deviation (s.d.) curves. Speed and stride length decreased
      and fore- and hind stance phase durations increased with collection resulting in
      no suspension in piaffe. The diagonal advanced placement was positive in all
      gaits except for piaffe. Most of the changes in forelimb angular patterns were
      effects of reduction in forelimb pendulation. The horses did not step under
      themselves more in collected trot, passage and piaffe than in trot in hand. The
      stifle and hock joints were more flexed at the start of the stance phase in
      piaffe and passage than in the other gaits. Flexion of the hock joint at the
      middle of the stance phase was largest in passage and piaffe. In spite of the
      limited number of horses the present study confirmed earlier observations of
      conformation and gaits in dressage horses. Hindlimb pendulation, femur and pelvis
      inclinations and elbow, carpal, stifle and hock joint angles seem to be the most
      significant angular measurements for dressage performance.

PMID- 8536663
TI  - Effects of glyceryl trinitrate (nitroglycerin) on pulmonary vascular pressures in
      standing thoroughbred horses.
AB  - Strenuously exercising Thoroughbreds exhibit a dramatic increase in pulmonary
      capillary blood pressure, which contributes to stress failure of pulmonary
      capillaries resulting in exercise induced pulmonary haemorrhage (EIPH). One
      strategy to prevent EIPH is, therefore, to lower the pulmonary capillary blood
      pressure of exercising horses. Recent work in several species suggests that
      nitric oxide plays a significant role in maintaining low vascular resistance in
      the pulmonary circulation; however, the effects of nitrovasodilators (which work
      via the same mechanism as nitric oxide) on equine pulmonary circulation have not
      been examined. The present study examined the effects of glyceryl trinitrate
      (nitroglycerin) on right atrial and pulmonary vascular pressures in 7 healthy
      sound Thoroughbred horses. Freshly prepared nitroglycerin solution was infused
      for 240 s into the right atrium of quietly standing Thoroughbreds at dose rates
      of 350, 700, 1400 and 2100 g/min in a randomised manner. All infusions were
      performed in duplicate. Heart rate, right atrial, pulmonary artery, pulmonary
      capillary and pulmonary artery wedge pressures were determined preinfusion, at 30
      s intervals during nitroglycerin infusions and at 60 s post infusion.
      Measurements were made using catheter mounted manometers whose in vivo signals
      had been matched with fluid-filled systems referenced at the level of the point
      of the shoulder. It was observed that nitroglycerin infusions caused a dose
      related increase in heart rate while dose related reductions occurred in the mean
      right atrial, pulmonary artery, pulmonary artery wedge and pulmonary capillary
      pressures. At 2100 micrograms/min, nitroglycerin induced reduction in pulmonary
      artery wedge pressure was significantly greater than that in the pulmonary artery
      pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536665
TI  - Rheumatoid factor, anti-heat shock protein (65 kDa) antibodies and anti-nuclear
      antibodies in equine joint diseases.
AB  - To consider the hypothesis that autoimmune mechanisms may contribute to the
      pathology of equine joint diseases, 3 autoimmune responses were assayed in sera
      and synovial fluids. IgM-rheumatoid factor and antibodies to heat shock protein
      65 kDa were determined by ELISA; anti-nuclear antibodies were assayed by indirect
      immunofluorescence to whole cell nuclear components. All parameters showed only
      modest increases, if any and not in a pattern related to disease, although some
      statistically significant increases were detected. Group analysis showed
      significantly elevated synovial fluid IgM-rheumatoid factor (IgM-RF) in horses
      with OA (P < 0.01), traumatised joints (P < 0.01) and articular fractured bones
      (P < 0.001). There was no significantly increased IgM-RF in the sera of horses
      with joint disorders compared to control horses. Significantly raised anti-heat
      shock protein molecular weight 65 kDa (HSP65) antibodies were only found in the
      synovial fluids of the horses with traumatised joints (P < 0.001). No
      correlations were found between the synovial fluid and sera levels of IgM-RF or
      anti-HSP65 antibodies. Synovial fluid anti-HSP65 antibody and IgM-RF levels
      positively correlated in the OCD (P < 0.001), fracture (P < 0.01) and synovitis
      (P < 0.05) groups. As antibodies to HSP65 correlated with IgG concentrations in
      synovial fluids, it is not possible to draw conclusions on HSP roles in joint
      disease pathogenesis. No serum anti-nuclear antibodies (ANA) were detected by
      immunofluorescence using rat liver and a human epithelial cell line (HEp-2) as
      substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536666
TI  - Effects of ketoprofen and phenylbutazone on chronic hoof pain and lameness in the
      horse.
AB  - The analgesic effects of the nonsteroidal anti-inflammatory drugs, ketoprofen
      (2.2 and 3.63 mg/kg bwt) and phenylbutazone (4.4 mg/kg bwt) were compared in 7
      horses with chronic laminitis. Hoof pain was quantified objectively by means of
      an electronic hoof tester and lameness was subjectively graded on a modified Obel
      scale. Ketoprofen at a dose of 3.63 mg/kg bwt (phenylbutazone equimolar dose)
      reduced hoof pain and lameness to a greater extent than the 2.2 mg/kg dose and
      phenylbutazone. These effects were still present at 24 h in 3 of the 4 pain
      tests, including lameness grade. These data suggest that ketoprofen at the dosage
      rate of 1.65 times the recommended therapeutic dose was more potent than
      phenylbutazone in alleviating chronic pain and lameness in horses.

PMID- 8536667
TI  - Clinical features of the 1992 outbreak of equine viral arteritis in Spain.
AB  - During 1992, a widespread outbreak of Equine viral arteritis (EVA) occurred at a
      riding establishment near Barcelona, Spain. A total of 31 out of 186 horses on
      the premises displayed clinical signs, most frequently, fever, depression, mild
      ventral and limb oedema and a vesicular-erosive stomatitis, with hypersalivation,
      petechiations and small ulcerations. Affected horses developed illness of varying
      severity with only a few exhibiting a severe form of the disease and no mortality
      was recorded. Haematological and blood biochemical examination the most severely
      affected horses revealed a thrombocytopenia, slight leucocytosis with
      neutrophilia, lymphopenia and eosinopenia, an increase in plasma fibrinogen and a
      small rise in serum proteins and indirect bilirubin values. Diagnosis was
      confirmed by demonstration of seroconversion to equine arteritis virus in acute
      and convalescent phase sera. Attempted isolation of the virus from citrated blood
      samples proved unsuccessful.

PMID- 8536668
TI  - Photic headshaking in the horse: 7 cases.
AB  - Seven horses with headshaking are described. No physical abnormalities were
      detected in any of the cases. Six of these horses had onset of clinical signs in
      the spring. The role of light was assessed by application of a blindfold or dark
      grey lens to the eyes, covering the eyes with a face mask and observing the horse
      in total darkness outdoors. Cessation of headshaking was observed with
      blindfolding (5/5 horses), night darkness outdoors (4/4 horses) and use of grey
      lenses (2/3 horses). Outdoor behaviour suggested efforts to avoid light in 4/4
      cases. The photic sneeze in man is suggested as a putative mechanism for equine
      headshaking. Five of 7 horses had improvement with cyproheptadine treatment (0.3
      mg/kg bwt b.i.d.). Headshaking developed within 2 calendar weeks of the same date
      for 3 consecutive years in one horse. Neuropharmacological alterations associated
      with photoperiod mechanisms leading to optic trigeminal summation are suggested
      as possible reasons for spring onset of headshaking.

PMID- 8536669
TI  - 99Tcm-HMPAO labelled leucocytes and their biodistribution in the horse: a
      preliminary investigation.

PMID- 8536670
TI  - Hypercalcaemia and erythrocytosis in a mare associated with a metastatic
      carcinoma.

PMID- 8536671
TI  - Persistence of kindling: effect of partial kindling, retention interval, kindling
      site, and stimulation parameters.
AB  - The kindling effect is generally thought to be highly persistent and possibly
      permanent, but little direct evidence is available to support this idea.
      Retention of amygdala kindling was examined after a 12-wk interval in groups of
      rats that had been electrically kindled to different seizure stages (stages 1, 3,
      or 5), or kindled by high intensity or low frequency (3 pulses per second)
      stimulation, or fully kindled and allowed a rest of 1-24 wk. The retention of
      hippocampal kindling after a 12-wk interval was also examined. Rekindling after a
      12-wk rest in the groups initially kindled to different seizure stages indicated
      that although there was evidence of erosion of the kindling effect in all groups,
      there were savings in all groups. There was also evidence of greater erosion in
      the afterdischarge response than in the convulsive response to the first
      stimulation after the interval. Although there was evidence of erosion of
      kindling during the 1-24-wk intervals, there was evidence of savings in all
      groups, none of which required more than a mean of 2.2 afterdischarges to
      rekindle to stage 5. Seizures kindled in the hippocampus were retained as well as
      those kindled in the amygdala, and seizures kindled using low frequency
      stimulation were retained as well as those kindled using conventional 60 pulses
      per second stimulation. We conclude that the effects of kindling the amygdala and
      hippocampus are highly persistent, and that the effects of kindling with low
      frequency stimulation are as persistent as kindling with conventional
      stimulation.

PMID- 8536672
TI  - Effects of anticonvulsants in a novel operant learning paradigm in rats:
      comparison of remacemide hydrochloride and FPL 15896AR to other anticonvulsant
      agents.
AB  - One of the primary undesired effects of anticonvulsant medication is an
      impairment in cognitive function, such as new learning ability. The purpose of
      the present study was to compare the effects of remacemide hydrochloride [(+/-)-2
      amino-N-(1-methyl-1,2,-diphenylethyl)acetamide monohydrochloride] and FPL 15896AR
      [(+)-alpha-phenyl-2-pyridine-ethanamide] to a number of anticonvulsant agents on
      an operant acquisition baseline. Remacemide hydrochloride is currently in
      clinical trials for epilepsy and FPL 15896AR is under development. In the present
      procedure, fasted, experimentally naive rats were placed into operant chambers in
      which food pellets were initially available under a Fixed-Ratio 1 (FR1) schedule
      of food presentation, and as lever pressing progressed, the FR value incremented.
      All drugs were tested in multiples of three and ten times their respective ED50
      values against maximal electroshock-induced seizure (MES) following p.o.
      administration. The drugs tested varied widely in their ability to disrupt
      acquisition of the lever-pressing task. Remacemide hydrochloride and a
      structurally related analog, FPL 15896AR, did not disrupt acquisition.
      Clonazepam, lamotrigine, MK-801, phenobarbital, felbamate, phenytoin, and
      carbamazepine increased the number of hours required to achieve FR3 (emit more
      than 100 responses) with respect to vehicle control performance. Of these,
      clonazepam, MK-801 and phenytoin produced robust enough disruption to result in
      significantly fewer reinforcers delivered over the 14-h operant session.

PMID- 8536673
TI  - An in vitro model of persistent epileptiform activity in neocortex.
AB  - An in vitro model of persistent epileptiform activity was developed to study the
      mechanisms involved in epileptogenesis. Extracellular recordings were obtained
      from rat neocortical slices exposed to magnesium-free solution for 2 h. During
      exposure to magnesium-free solution spontaneous epileptiform activity consisting
      of interictal bursting and ictal-like discharges were observed. Interestingly,
      this activity persisted for hours after the slices were returned to magnesium
      containing control solution. The N-methyl-D-aspartate (NMDA) receptor antagonist
      CPP prevented the development of the epileptiform activity, while the non-NMDA
      receptor antagonist CNQX abolished the epileptiform discharge that persisted
      after slices were returned to control solution. These findings suggest there are
      two distinct phases in the development of epileptic activity in this model,
      namely, induction (mediated by NMDA receptor activity) and maintenance (supported
      largely by non-NMDA receptor activity). The similarities and possible parallels
      between the mechanisms underlying this epileptogenesis and other forms of use
      dependent modification of synaptic excitation, such as long-term potentiation,
      are discussed. This in vitro model of neocortical epileptogenesis may provide
      insights into the events underlying the development of clinical partial epilepsy.

PMID- 8536674
TI  - Experimentally induced disorders of neuronal migration produce an increased
      propensity for electrographic seizures in rats.
AB  - Disorders of neuronal migration in humans are associated with intractable
      epilepsy and some evidence suggests a causal relationship. This study evaluated
      electroencephalograms (EEG) of rats with experimentally induced disorders of
      neuronal migration. Fetal Sprague-Dawley rats were exposed to 196 cGy external
      irradiation on days 16 and 17 of gestation. This produced adult offspring with
      diffuse cortical dysplasias, agenesis of the corpus callosum, periventricular
      heterotopias, and dispersion of the pyramidal cell layer of the hippocampus.
      Epidural electrodes were implanted in four experimental (irradiated on
      gestational day 17) and four control rats. EEGs were recorded without anesthesia
      and in the presence of the anesthetic agents ketamine, acepromazine, and
      xylazine. In the presence of acepromazine, xylazine, or a combination of the two
      drugs, two of the four experimental rats had prolonged ictal activity on EEG. In
      one of the rats the ictal activity progressed to electrographic status
      epilepticus. Ketamine alone did not produce ictal EEG activity. None of the
      control rats demonstrated ictal activity under any treatment condition. This
      study demonstrates that disorders of neuronal migration are associated with an
      increased propensity for seizures in the presence of certain sedating agents.

PMID- 8536675
TI  - Response of human epileptic temporal lobe cortical blood flow to
      hyperventilation.
AB  - Bilateral long-term surface cortical cerebral blood flow (CBF) and
      electrocorticographic (ECoG) monitoring were performed in eight patients with
      complex partial seizures. In each patient, the epileptic temporal lobe was
      localized using ictal ECoG. Mean seizure interval (frequency-1) off
      anticonvulsant medication, a clinical measure of epileptogenicity, was 1.0 +/-
      0.3 h (range: 0.4 to 2.5 h). During 13 interictal hyperventilation periods, 3.6
      +/- 0.6 min in duration, the mean decrease in epileptic and nonepileptic temporal
      cortical CBF was 13.7 +/- 2.3 versus 6.4 +/- 1.9 ml/(100 g min) (t = 2.230, d.f.
      = 16, P < 0.05), representing 20.9% and 10.8% reduction from baseline CBF during
      hyperventilation, respectively. Seizure interval decreased (i.e. frequency
      increased) with increasing magnitude of seizure focus CBF reduction during
      hyperventilation. Seizure interval was significantly correlated with epileptic
      temporal lobe CBF decrease during hyperventilation (R = 0.763, d.f. = 5, P <
      0.05). The data suggest that, compared to nonepileptic brain, epileptic temporal
      lobe is particularly prone to hypoperfusion during hyperventilation.
      Epileptogenicity is a function of this seizure focus susceptibility to ischemia.
      The finding of abnormal seizure focus autoregulation during hyperventilation has
      implication for epileptic focus localization with cerebral blood flow analysis.

PMID- 8536676
TI  - Retrospective study of vigabatrin and psychiatric behavioural disturbances.
AB  - Vigabatrin (VGB) is an effective add-on anti-epileptic drug. The major serious
      adverse drug reactions (ADRs) are behavioural and psychiatric disturbances. This
      study does not support the view that a previous history of behavioural and
      psychiatric features increases the risk of behavioural/psychiatric ADRs (relative
      risk 1.23, 95% CI 0.57-2.66, P = 0.61). The results suggest that a low starting
      does of vigabatrin does not reduce the risk of psychiatric and behavioural ADRs
      (P = 0.31) or prevent a more overt psychotic reaction from occurring.

PMID- 8536677
TI  - Seizure frequency and CSF parameters in a double-blind placebo controlled trial
      of gabapentin in patients with intractable complex partial seizures.
AB  - Gabapentin (GBP) is a non-protein-bound gamma amino acid which is not subjected
      to metabolic degradation in man. As part of a placebo-controlled double-blind
      study, patients suffering from intractable complex partial seizures with or
      without secondary generalization were followed with lumbar punctures at baseline
      and after three months of GBP treatment (900 mg/day or 1200 mg/day).
      Cerebrospinal fluid (CSF) was analyzed for concentrations of GBP, amino acids
      including GABA, homovanillic acid (HVA), and 5 hydroxyindoleacetic acid (5-HIAA).
      The results indicate that there were no changes in the selected amino acids, HVA,
      or 5-HIAA after GBP treatment. At steady state the CSF/plasma ratios of GBP
      ranged from 0.056 to 0.34, indicating that there may be some type of active out
      transport of GBP across the blood-brain barrier. No linear relationship was
      observed between plasma and CSF levels in these patients.

PMID- 8536678
TI  - Energised (entatic) states of groups and of secondary structures in proteins and
      metalloproteins.
AB  - In this review I have examined the functional value of selected states of
      isolated groups in proteins energised away from their expected ground states
      whether they are observed with or without energy perturbation of larger parts of
      a protein structure. These energisations, found in the absence of substrates, are
      called 'entatic states of groups' [Vallee, B. L. & Williams, R. J. P. (1968)
      Proc. Natl Acad. Sci. USA 59, 498-505]. A group can be part of an amino acid or
      any bound metal ion or cofactor. In some particular cases the apoprotein, where
      the energised metal ion or cofactor has been removed, or the protein in which the
      energised amino acid has been replaced, has the same back-bone structure as the
      holoprotein and even side-chains are only slightly adjusted. This case is quite
      different from a condition of a group simultaneously energised with a protein
      fold, due to their combination, and which therefore involves conformational
      change in the protein and the group and which may adjust the group while the
      protein tightens. The final condition is again stable but removal of the group
      now must result in a reversed protein conformation change. This simultaneous
      energisation of both the adjustable protein and the group can be local, as in an
      induced fit or more extensive when it can be likened in some cases to a
      stretching by rack action, or may involve a change from an almost random to a
      structured protein when the group is energised in a very limited way. The various
      energisations must not be confused since they differ functionally. The first can
      give rise to optimal heightened catalytic (or other functional) potential of the
      local group but cannot be connected either to excitation of other parts of a
      protein as in induced fitting, or to a relay of energy (larger conformational
      change) in the protein. Clearly it restricts the rate of exchange of a group.
      Induced fit can also give rise to group activation, though to a somewhat reduced
      degree, while increasing exchange rate. A device such as a rack may rather give
      rise to a mechanical activity (message transmission), which is relayed a large
      distance into the protein, and can only give considerably lower activation of
      individual groups but exchange may now be fast. The final case involves very
      modest energisation of the group with gross rearrangement and energisation of the
      protein and may be associated with storage or carrier functions. The groups upon
      which I concentrate are metal ions since detailed electronic and structural
      knowledge of their ground states are well known, allowing energised states to be
      easily detected, but the ideas apply equally to organic side-chains of proteins
      as will be shown. A further energisation can arise from the addition of a
      substrate to each kind of protein. In fact all the ideas of energisation
      applicable to groups having cyclic activity in permanent features of protein
      structure are equally well applied to substrate binding or conversion of
      substrates through excited states to products.

PMID- 8536679
TI  - Thermostability of a nuclear-targeted luciferase expressed in mammalian cells.
      Destabilizing influence of the intranuclear microenvironment.
AB  - Protein denaturation and aggregation are most likely the cause for the noxious
      effects of heat shock. There are some indications that the nucleus is one of the
      most sensitive cellular compartments. To test the possibility that the
      intranuclear microenvironment might be detrimental to the heat stability of
      proteins, we compared the in situ thermal stability of a reporter protein
      localized in the nucleus or in the cytoplasm. A recombinant firefly (Photynus
      pyralis) luciferase carrying a point mutation in the C-terminal domain remains in
      the cytoplasm (cyt-luciferase). A nuclear localization sequence was fused to the
      N-terminal domain of cyt-luciferase; the resulting nuc-luciferase was efficiently
      targeted to the cell nucleus. In both cases, decreased luciferase activity and
      solubility were found in lysates from heat-shocked cells. These characteristics
      were taken as an indication of thermal denaturation in situ. The heat-inactivated
      luciferases were partially reactivated during recovery after stress, indicating
      the capacity of both the cytoplasmic and nuclear compartments to reassemble
      proteins from an aggregated state. Although both the nuc- and the cyt-luciferases
      were heat inactivated at similar rates in vitro, nuc-luciferase was more
      susceptible to thermal denaturation in situ compared to cyt-luciferase. This
      observation suggests that the microenvironment of an intracellular compartment
      may modulate the thermal stability of proteins. The local concentration might be
      one element of this microenvironment affecting the heat-stability of proteins. In
      cells made thermotolerant by a priming shock, the thermal inactivation of the
      recombinant luciferases occurred at a slower rate during a second challenging
      stress. However, this decreased thermal sensitivity was less pronounced for the
      nuc-luciferase (threefold) than for the cyt-luciferase (sevenfold). The nuclear
      luciferase might become a useful tool to investigate the action of molecular
      chaperones in the nucleus.

PMID- 8536680
TI  - Fatty acids and fibrates are potent inducers of transcription of the
      phosphenolpyruvate carboxykinase gene in adipocytes.
AB  - Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) plays a critical role in
      adipose tissue glyceroneogenesis. We have previously shown that transcription of
      the PEPCK gene was stimulated by isoprenaline and retinoic acid in 3T3-F442A
      adipocytes. We also showed that oleate increased PEPCK mRNA. Here, we analysed
      the effect that fatty acids of various chain lengths and unsaturation degrees
      exerted on PEPCK gene expression in 3T3-F442A adipocytes. When maintained in
      serum-free, glucose-free medium, differentiated cells responded to unsaturated
      long-chain fatty acids by a large increase in PEPCK mRNA whereas saturated fatty
      acids were inefficient. A maximum fivefold stimulation by oleate was attained at
      4 h of treatment with 1 mM fatty acid bound to albumin in a 6:1 ratio. The poly
      unsaturated very long-chain fatty acid all-cis-4,7,10,13,16,19-docosahexaenoic
      acid (C22:6) was even more potent and produced a tenfold increase. The expression
      of the genes encoding glycerol-3-phosphate dehydrogenase, hormone-sensitive
      lipase or actin remained unaffected by oleate exposure. A 4-h treatment by the
      hypolipidemic drug clofibrate, 0.5-2 mM, also produced a large (3-9-fold)
      increase in PEPCK mRNA. When used at non-saturating concentrations, oleate and
      clofibrate acted in an additive manner. At maximally effective concentrations,
      additivity was lost, suggesting that fatty acids and fibrates might act through
      similar mechanisms. Nuclear transcription experiments showed that oleate and
      clofibrate stimulated the transcription rate of the gene. 3T3-F442A cells were
      stably transfected with a plasmid containing the base pairs -2100 to +69 of the
      PEPCK gene promoter fused to the chloramphenicol acetyltransferase gene. These
      differentiated stable transfectants responded to oleate and clofibrate by a
      specific increase in chloramphenicol acetyltransferase activity. Adipocytes
      express various isoforms of peroxisome-proliferator-activated receptors that can
      be activated by fibrates and fatty acids. Potential recognition sequences for
      peroxisome-proliferator-activated receptors are present in the -2100 to +69
      fragment of the PEPCK gene promoter. Thus, this gene represents an ideal
      molecular target for understanding the complex transcriptional control exerted by
      fatty acids and peroxisome proliferators.

PMID- 8536681
TI  - Human monoclonal antibodies to cytomegalovirus. Characterization and recombinant
      expression of a glycoprotein-B-specific antibody.
AB  - Human monoclonal antibodies (mAb) to human cytomegalovirus (HCMV) were
      established from spleen cells of a HCMV-positive donor. The antibodies (gamma 3,
      lambda) secreted from a stable heterohybridoma cell line were further
      characterized by immunoprecipitation and immune-fluorescence microscopy using
      HCMV infected cells and recombinant cell lines expressing HCMV glycoprotein B.
      The antibody reacted with the entire glycoprotein B or the extracellular domain
      expressed as glycoprotein-B--beta-galactosidase fusion protein in the native
      state, but the antibody was not neutralizing HCMV. Denatured and reduced forms of
      glycoprotein B were not recognized by this antibody, however, native glycoprotein
      B on the surface of infected cells was detected efficiently. The genes encoding
      the Fab part of the antibody were cloned and expressed in Escherichia coli.
      Recombinant Fab fragments specifically binding the extracellular domain of
      glycoprotein B could easily be isolated from the periplasmic space. Recombinant
      antibodies provide the opportunity to modify effector functions and to add tags
      to diagnostic antibodies for more efficient detection of CMV-infected cells.

PMID- 8536682
TI  - Characterization of the cDNA and pattern of expression of a new gene over
      expressed in human hepatomas and colonic tumors.
AB  - A cDNA clone of 6.449 kb ch-TOG (for colonic and hepatic tumor over-expressed
      gene) initially selected from various human libraries and completed by 5' rapid
      amplification of cDNA ends (RACE) PCR is described. The original cDNA clone was
      extracted from an expression library constructed from a human tumoral brain. This
      library was screened with an antibody raised against the cytochrome P450tu that
      was shown to be over-expressed in chemically induced mouse hepatic tumors. Using
      this cDNA as a probe, a full-length cDNA was characterized. Its nucleotide
      sequence shows no significant similarity with any of the gene sequences collected
      in the various DNA data bases. The translation of the larger open reading frame
      leads to a putative protein of 1972 amino acids (molecular mass = 218453 Da).
      Hybridization analyses on Southern blot and on metaphase chromosomes indicate
      that this gene is present as a single copy in the genome and is localized on the
      short arm of chromosome 11. ch-TOG transcripts are present in several human
      tissues. Over-expression of ch-TOG in neoplastic liver and colon compared with
      the corresponding normal corresponding tissues is demonstrated. The level of the
      expression of ch-TOG transcripts was also studied in the various differentiation
      stages of the human colonic adenocarcinoma cell line Caco-2.

PMID- 8536683
TI  - Post-translational heterocyclic backbone modifications in the 43-peptide
      antibiotic microcin B17. Structure elucidation and NMR study of a 13C,15N
      labelled gyrase inhibitor.
AB  - Microcin B17 (McB17), the first known gyrase inhibitor of peptidic nature, is
      produced by ribosomal synthesis and post-translational modification of the 69
      residue precursor protein by an Escherichia coli strain. To elucidate the
      chemical structure of the mature 43-residue peptide antibiotic, fermentation and
      purification protocols were established and optimized which allowed the isolation
      and purification of substantial amounts of highly pure McB17 (non-labelled, 15N
      labelled and 13C/15N-labelled peptide. By ultraviolet-absorption spectroscopy.
      HPLC-electrospray mass spectrometry and GC-mass spectrometry, amino acid
      analysis, protein sequencing, and, in particular, multidimensional NMR, we could
      demonstrate and unequivocally prove that the enzymic modification of the
      precursor backbone at Gly-Cys and Gly-Ser segments leads to the formation of 2
      aminomethylthiazole-4-carboxylic acid and 2-aminomethyloxazole-4-carboxylic acid,
      respectively. In addition, two bicyclic modifications 2-(2
      aminomethyloxazolyl)thiazole-4-carboxylic acid and 2-(2
      aminomethylthiazolyl)oxazole-4-carboxylic acid were found that consist of
      directly linked thiazole and oxazole rings derived from one Gly-Ser-Cys and one
      Gly-Cys-Ser segment. Analogous to the thiazole and oxazole rings found in
      antitumor peptides of microbial and marine origin, these heteroaromatic ring
      systems of McB17 presumably play an important role in its gyrase-inhibiting
      activity, e.g. interacting with the DNA to trap the covalent protein-DNA
      intermediate of the breakage-reunion reaction of the gyrase.

PMID- 8536684
TI  - The handedness of the subunit arrangement of the nicotinic acetylcholine receptor
      from Torpedo californica.
AB  - Cross-linking an alpha-neurotoxin with a known three-dimensional structure and
      with photoactivatable groups in known positions to native membrane-bound
      acetylcholine receptor reveals its quaternary structure, including the handedness
      of its circular subunit arrangement. Photolabelling with alpha-neurotoxin
      carrying the photoactivatable group at position Lys46 is inhibited by the
      competitive antagonist (+)-tubocurarine in a biphasic manner, indicating that it
      reacts with both alpha-subunits that were shown to have different affinities for
      this antagonist [Neubig, R. R. & Cohen, J. B. (1979) Biochemistry 18, 5464-5475].
      Lys46 is located on loop III of the neurotoxin. The other information necessary
      for the elucidation of the handedness was provided by the recent finding that the
      central loop of the toxin (loop II) is oriented towards the central pore of the
      receptor, securing the overall orientation of the bound toxin [Machold, J.,
      Utkin, Y. N., Kirsch, D., Kaufmann, R., Tsetlin, V. & Hucho, F. (1995b) Proc.
      Natl Acad. Sci. USA 92, 7282-7286]. Looking at the receptor from the synaptic
      side of the postsynaptic membrane, it was concluded that the clockwise subunit
      arrangement is alpha H-gamma-alpha L-delta-beta (alpha H and alpha L are the
      alpha-subunits binding (+)-tubocurarine with high and low affinity,
      respectively). Its mirror image alpha alpha L-gamma-alpha H-beta-delta could thus
      be excluded.

PMID- 8536685
TI  - Structure/function relationships in the hemoglobin components from moray (Muraena
      helena).
AB  - Concerning the number and type of the hemoglobin components, the moray Muraena
      helena is characterized by three different phenotypes whose frequencies are
      nearly identical. Thus, the cathodal component is present in all individuals,
      whereas one or both of two anodal components may be present in the same
      phenotype. These components have been separated by chromatography. The oxygen
      binding properties of the purified hemoglobin components have been studied in the
      absence and presence of saturating concentrations of ATP or GTP and as a function
      of pH. The cathodal component shows an intrinsic O2 affinity four times higher
      than that of both anodal components, a very small Bohr effect and a significant
      decrease in O2 affinity upon addition of ATP and GTP (three and four times
      respectively with respect to stripped conditions), the latter being more
      effective than the former over the entire pH range examined. The anodal
      components do not appear functionally distinguishable and show the presence of an
      enhanced Bohr effect (Root effect) that is under the strict control of nucleotide
      triphosphates ATP, GTP, which, unlike in the cathodic component, exert the same
      effect on oxygen affinity. The complete sequence of the beta chains of the
      cathodal and of one of the anodal components have been determined. The possible
      molecular basis of these different functional characteristics are discussed in
      the light of the globin sequence and of those amino acid residues which are known
      to be responsible of hemoglobin functional behaviour.

PMID- 8536686
TI  - The sequence of arrestins from rod and cone photoreceptors in the frogs Rana
      catesbeiana and Rana pipiens. Localization of gene transcripts by reverse
      transcription polymerase chain reaction on isolated photoreceptors.
AB  - Members of the arrestin protein family are known to participate in the
      inactivation of rhodopsin and other heptahelical receptors. Arrestins bind to the
      activated and phosphorylated state of these receptors, consequently blocking the
      ability of the receptors to activate the guanine-nucleotide-binding protein (G
      protein). We have determined the sequences of four retinal arrestins from two
      species of frog, Rana catesbeiana and Rana pipiens. Using polymerase chain
      reaction on reverse-transcribed mRNA isolated from single photoreceptor cells, we
      show that two of these arrestins are from rod photoreceptors and two rod
      photoreceptors and two are from cone photoreceptors. Comparison of these
      arrestins with the twenty known arrestin sequences identifies three regions of
      the protein that are well conserved across all phylogenetic groups. These regions
      may function in the binding of the arrestin to the heptahelical receptors. In
      addition, the Rana arrestins contain a uniquely acidic C-terminal sequence.

PMID- 8536687
TI  - Purification and two-dimensional crystallization of bacterial cytochrome
      oxidases.
AB  - A novel strategy which employes chromatography on an immobilized metal ion has
      been developed for the purification of bacterial cytochrome c and quinol
      oxidases. Many bacterial oxidase complexes appear to have a natural affinity to
      bind to the chelated copper ion. A combination of three different chromatographic
      principles (anion exchange, metal-affinity and gel filtration) makes an effective
      tool chest for the preparation of homogeneous and protein-chemically pure
      bacterial oxidases. These preparations have been used for two-dimensional
      crystallization. Until now, crystals have been obtained using the Paracococcus
      denitrificans and Rhodobacter sphaeroides cytochrome aa3 and the Escherichia coli
      cytochrome bo. The crystals diffract to approximately 2.5 nm in negative stain
      and have potential for further structural studies.

PMID- 8536688
TI  - Purification and properties of NAD(P)H: (quinone-acceptor) oxidoreductase of
      sugarbeet cells.
AB  - NAD(P)H:(quinone-acceptor) oxidoreductase [NAD(P)H-QR], a plant cytosolic
      protein, was purified from cultured sugarbeet cells by a combination of ammonium
      sulfate fractionation, FPLC Superdex 200 gel filtration, Q-Sepharose anion
      exchange chromatography, and a final Blue Sepharose CL-6B affinity chromatography
      with an NADPH gradient. The subunit molecular mass is 24 kDa and the active
      protein (94 kDa) is a tetramer. The isoelectric point is 4.9. The enzyme was
      characterized by ping-pong kinetics and extremely elevated catalytic capacity. It
      prefers NADPH over NADH as electron donor (kcat/Km ratios of 1.7 x 10(8) M-1 S-1
      and 8.3 x 10(7) M-1 S-1 for NADPH and NADH, respectively, with benzoquinone as
      electron acceptor). The acridone derivative 7-iodo-acridone-4-carboxylic acid is
      an efficient inhibitor (I0.5 = 5 x 10(-5) M), dicumarol is weakly inhibitory. The
      best acceptor substances are hydrophilic, short-chain quinones such as ubiquinone
      0 (Q-0), benzoquinone and menadione, followed by duroquinone and ferricyanide,
      whereas hydrophobic quinones, cytochrome c and oxygen are reduced at negligible
      rates at best. Quinone acceptors are reduced by a two-electron reaction with no
      apparent release of free semiquinonic intermediates. This and the above
      properties suggest some relationship of NAD(P)H-QR to DT-diaphorase, an animal
      flavoprotein which, however, has distinct structural properties and is strongly
      inhibited by dicumarol. It is proposed that NAD(P)H-QR by scavenging unreduced
      quinones and making them prone to conjugation may act in plant tissues as a
      functional equivalent of DT-diaphorase.

PMID- 8536689
TI  - Pigment-protein complexes from the photosynthetic membrane of the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - Photosystem I and II core complexes were resolved in a single step from the
      thylakoid membrane of Synechocystis sp. PCC 6803 by using a mild solubilization
      procedure in dodecyl beta-D-maltoside and Deriphat/PAGE. For each photosystem,
      two green bands were obtained containing oligomeric and monomeric forms of the
      core complexes of either photosystem. The oligomers are likely to be trimers in
      the case of photosystem I and dimers for photosystem II. The absorption spectra,
      polypeptide and pigment composition of green bands corresponding to either
      photosystem I or photosystem II were identical for monomeric and oligomeric
      forms. The cytochrome b-559 content of photosystem II was evaluated to be one
      cytochrome b-559/reaction centre both in the monomeric and dimeric forms. Two new
      15-kDa and 22-kDa carotenoid-binding protein were isolated and their polypeptides
      purified to homogeneity.

PMID- 8536690
TI  - The mechanism of action of hepatic sympathetic nerves on ketone-body output from
      perfused rat liver. The effect of the interaction of noradrenaline with ATP on
      the release of beta-hydroxybutyrate.
AB  - The regulatory mechanism of ketone-body output by the hepatic sympathetic nerves
      was studied in rat liver perfused in situ. Enrichment of the perfusion medium
      with 1 mM octanoate increased the basal ketone-body output from the liver up to
      1.5 mumol.min-1.g liver-1. Under these conditions, electrical stimulation of the
      hepatic nerves (20 V, 20 Hz, 2 ms) decreased the output of both acetoacetate and
      beta-hydroxybutyrate, and was accompanied by an accumulation of beta
      hydroxybutyrate in the liver. The effects of nerve stimulation were inhibited by
      the alpha 1-antagonist bunazosin (10 microM). However, noradrenaline, a typical
      sympathetic neurotransmitter, at a concentration of 1 microM decreased the output
      of acetoacetate but did not affect beta-hydroxybutyrate output. Prostaglandin F2
      alpha at a concentration of 10 microM produced an effect similar to treatment
      with noradrenaline, without a decrease in beta-hydroxybutyrate output. ATP at 50
      microM, however, decreased the output of both acetoacetate and beta
      hydroxybutyrate and increased the tissue concentration of beta-hydroxybutyrate,
      mimicking the effect of nerve stimulation. Moreover, in the presence of 0.2
      microM ATP, a concentration that produced neither metabolic nor hemodynamic
      changes, noradrenaline (1 microM) was shown to decrease the beta-hydroxybutyrate
      output. These results indicate the possible involvement of ATP in the action of
      hepatic sympathetic nerves on beta-hydroxybutyrate output from the liver,
      presumably through its interaction with noradrenaline.

PMID- 8536691
TI  - Inhibition of human glutathione reductase by S-nitrosoglutathione.
AB  - S-Nitrosoglutathione (GSNO) represents a major transport form in nitric oxide
      (NO) in biological systems. Since NO and GSNO have been shown to modulate the
      function of various proteins, we studied the influence of GSNO and other NO
      donors on human glutathione reductase (GR). Catalyzing the reaction
      NADPH+GSSG+H(+)-->NADP(+) + 2 GSH, the dimeric flavoprotein GR is the central
      enzyme of the glutathione redox metabolism. GSNO was found to inhibit crystalline
      erythrocyte GR in two ways: (a) as a reversible inhibitor GSNO is competitive
      with glutathione disulfide (GSSG), the Ki being appr. 0.5 mM; (b) as an
      irreversible inhibitor; after 1 h (3 h) incubation with 1 mM GSNO, GR (2.5 U/ml,
      representing intraerythrocytic concentrations) was inhibited by 70% (90%). This
      inhibition depended on the presence of NADPH and could not be reversed by
      dilution nor by reducing agents. Absorption spectra indicate that the charge
      transfer interaction between Cys63 and the flavin is abolished by this
      modification. In a GR sample inhibited by 90% with GSNO, the Km values for the
      substrates GSSG and NADPH were not significantly changed nor did the modification
      induce oxidase activity of the enzyme. GSNO was found not to be a substrate in
      the forward reaction of GR. This implies that GSNO is not accounted for by
      methods which employ GR for determining total glutathione. Incubating isolated GR
      for 60 min with other NO donors, namely 1 mM sodium nitroprusside or 1 mM S
      nitroso-N-acetyl-DL-penicillamine (SNAP), resulted in only 25% and 10%
      inhibition, respectively. This attests to a specific affinity of GSNO to the
      enzyme. GSNO inhibition patterns comparable to purified authentic GR were
      obtained for purified recombinant GR, a GR mutant lacking the 15 N-terminal amino
      acids including Cys2, and for the enzyme present in diluted fresh haemolysates
      (0.02 U/ml); in concentrated haemolysates the inhibition was less pronounced. GR
      of intact erythrocytes was not affected when exposed to GSNO in the medium. Our
      results suggest that the irreversible inhibition of GR by GSNO involves
      nitrosylation of Cys63 and/or Cys58 at the catalytic site of the enzyme. To
      further investigate the mechanism of inactivation we have crystallized GSNO
      modified GR for X-ray diffraction analysis.

PMID- 8536692
TI  - Basic fibroblast growth factor controls the expression and molecular structure of
      heparan sulfate in corneal endothelial cells.
AB  - Cultured bovine corneal endothelial cells express 5-8 ng basic fibroblast growth
      factor (bFGF)/mg cell protein and distribute it between the intracellular and
      pericellular compartment. Confluent cultures retain approximately 80% of the
      total bFGF intracellularly, whereas 20% is present in the pericellular (trypsin
      releasable) compartment. No bFGF can be detected in the culture medium. The
      presence of 1-2 ng/ml medium of endogenous or exogenous (human recombinant) bFGF
      is sufficient to support cell growth. Simultaneously, cells incorporate
      [35S]sulfate and [3H]glucosamine into the sulfated proteoglycans associated with
      the cell layer at a rate that is three times higher than in the absence of bFGF.
      The enhanced proteoglycan synthesis is accompanied by a shift in proteoglycan
      distribution. In control cells, cell-associated heparan sulfate accounts for
      about 30% of the total glycosaminoglycans, whereas under the influence of bFGF
      the amount of heparan sulfate increases to approximately 60%. At the same time,
      the molecular structure of the heparan sulfate molecule undergoes bFGF-specific
      changes as indicated by the [35S]oligosaccharide pattern generated by
      heparitinase I degradation. The proportion of [35S]oligosaccharides with greater
      than six monosaccharides decreases on account of disaccharides and
      tetrasaccharides under the influence of bFGF. Pretreatment of bFGF with
      neutralizing antibodies against bFGF abolishes its biological activity. The
      results suggest a bFGF-dependent change in the rate of synthesis and structural
      features of the membrane-associated heparan sulfate in corneal endothelial cells.
      The modification of the heparan sulfate structure could influence its bFGF
      binding and antiproliferative activity.

PMID- 8536693
TI  - Expression of a biologically active murine tissue inhibitor of metalloproteinases
      1 (TIMP-1) in baculovirus-infected insect cells. Purification and tissue
      distribution in the rat.
AB  - Murine tissue inhibitor of metalloproteinases-1 (mTIMP-1) was expressed in
      baculovirus-infected insect cells (Sf9). The protein secreted into the culture
      medium was purified to homogeneity by means of heparin-Sepharose CL-6B and FPLC.
      The purified protein showed metalloproteinase-inhibitory activity in two
      independent assays: reverse zymography and inhibition of collagenase activity.
      Digestion of the recombinant TIMP-1 with peptide-N-glycanaseF revealed that both
      N-glycosylation sites are used. 125I-mTIMP-1 intraveneously injected into a male
      Sprague Dawley rat disappeared within 2 min from the circulation. 5 min after
      injection more than 50% of the 125I-mTIMP-1 were found in the liver and 20% in
      the kidneys. At later times, trichloroacetic-acid-soluble material accumulated in
      the intestinal tract.

PMID- 8536694
TI  - Complete nucleotide sequence, expression, and chromosomal localisation of human
      mixed-lineage kinase 2.
AB  - Protein kinases play pivotal roles in the control of many cellular processes. In
      a search for protein kinases expressed in human epithelial tumour cells, we
      discovered two members of a novel protein kinase family [Dorow, D. S., Devereux,
      L., Dietzsch, E. & de Kretser, T. A. (1993) Eur. J. Biochem. 213, 701-710]. Due
      to the unique mixture of structural domains within their amino acid sequences, we
      named the family mixed-lineage kinases (MLK). We initially isolated clones
      encoding partial cDNAs of MLK1 and 2 from a human colonic cDNA library. The MLK2
      cDNA was subsequently used to screen a human brain cDNA library and we have now
      cloned and sequenced a 3454-bp cDNA encoding the full-length MLK2 protein. The
      predicted MLK2 polypeptide has 954 amino acids and contains a src homology 3
      (SH3) domain, a kinase catalytic domain, a double leucine zipper and basic
      domain, and a large C-terminal domain. The 22-amino-acid N-terminal region has
      four glutamic acid residues immediately following the initiator methionine.
      Beginning at amino acid 23, the 55-amino-acid SH3 domain contains a 5-amino-acid
      insert in a position corresponding to inserts of 6 and 15 residues in the SH3
      domains of n-src and the phosphatidylinositol 3'-kinase. Adjacent to the SH3
      domain is a kinase catalytic domain with conserved motifs associated with both
      serine/threonine and tyrosine specificity. Beginning nine residues C-terminal to
      the catalytic domain, there are two leucine/isoleucine zippers separated by a 13
      amino-acid spacer sequence and followed by a stretch of basic residues. The
      polybasic sequence contains a motif that is similar to nuclear localisation
      signals from several proteins. The C-terminal domain is composed of 491 amino
      acids of which 17% are serine or threonine and 16% are proline. This domain also
      has a biased ratio of basic to acidic amino acids with a calculated pI of 9.38.
      When used as a probe to examine mRNA expression in human tissues, a MLK2 cDNA
      hybridised to a species of 3.8 kb that was expressed at highest levels in RNA
      from brain and skeletal muscle. The 3454-bp cDNA was also used for fluorescence
      in situ hybridisation to localise the MLK2 gene to human chromosome 19 q13.2.

PMID- 8536695
TI  - The effect of pH on the folding and stability of the myosin rod.
AB  - The far-ultraviolet circular dichroism and fluorescence emission intensities of
      the myosin rod were studied at pH 2-11, in the absence and presence of guanidine
      hydrochloride. The protein kept its helicity in this pH range. Its stability in
      the denaturant was higher at acidic pH than at pH 7. This may be due to favorable
      interactions involving protonated glutamic acid residues at the interface of the
      two alpha-helical chains of the molecule. At alkaline pH, the fluorescence of the
      myosin rod was quenched, and the tryptophan region of the protein became less
      stable in the presence of guanidine hydrochloride, due to ionization of tyrosine
      residues or other amino acids close to tryptophans in the double-helix
      arrangement.

PMID- 8536696
TI  - A comparative study of the inactivation of wild-type, recombinant and two mutant
      horseradish peroxidase isoenzymes C by hydrogen peroxide and m
      chloroperoxybenzoic acid.
AB  - The mechanism-based inactivation of four horseradish peroxidase (HRP-C) enzyme
      variants has been studied kinetically with either hydrogen peroxide or the
      xenobiotic m-chloroperoxybenzoic acid (mClO2-BzOH) as sole substrate. The
      concentration and time dependence of inactivation was investigated for the wild
      type plant enzyme (HRP-C), the unglycosylated recombinant enzyme (HRP-C*), and
      two site-directed mutants with Phe143 replaced by Ala ([F143A]HRP-C*) or Arg38
      replaced by Lys ([R38K]HRP-C*). The number of turnovers (r) of H2O2 required to
      completely inactivate the enzymes was found to vary between the different enzymes
      with HRP-C being most resistant to inactivation (r = 625), HRP-C* and [F143A]HRP
      C* being approximately twice as sensitive (r = 335 and 385, respectively) in
      comparison, and [R38K]HRP-C* being inactivated much more easily (r = 20). In the
      cases of HRP-C* and [F143A]HRP-C*, compared to HRP-C the differences were due to
      the absence of glycosylation on the exterior of the proteins, whilst the
      [R38K]HRP-C* variant exhibited a distinct mechanistic difference. When mClO2BzOH
      was used as the substrate the differences in sensitivity to inactivation
      disappeared. The values of r were all around 3 reflecting the strong affinity of
      mClO2BzOH for the active site. The apparent rate constant for inactivation by
      H2O2 was found to be about twofold higher in [R38K]HRP-C* than the other enzymes
      and the catalytic constant for turnover of H2O2 was approximately ten times
      lower. The affinity of compound I for H2O2 leading to the formation of a
      transitory intermediate implicated in the inactivation of peroxidase decreased in
      the order HRP-C, HRP-C*, [F143A]HRP-C*, [R38K]HRP-C*.

PMID- 8536697
TI  - Receptor-mediated regulation of leukotriene C4 synthase activity in human
      platelets.
AB  - Human platelets possess a specific membrane-bound leukotriene (LT) C4 synthase,
      which catalyzes the conversion of LTA4 to LTC4. Stimulation of the receptors for
      thrombin, collagen or thromboxane A2 provoked inhibition of this enzyme, as
      judged by suppressed transformation of exogenous LTA4 to LTC4. Similarly, direct
      activation of protein kinase (PK) C with nanomolar concentrations of 4 beta
      phorbol 12-myristate 13-acetate (PMA) inhibited the production of LTC4. Kinetic
      studies demonstrated that the inhibition induced by thrombin and PMA was non
      competitive. Elevation of intracellular cAMP levels with carbacyclin did not
      affect basal LTC4 formation, but abolished the attenuation of platelet LTC4
      synthase activity induced by the thromboxane receptor agonist U-46619. The
      unselective protein kinase inhibitor staurosporine prevented both receptor
      mediated and PMA-induced suppression of LTC4 formation. In contrast, two
      selective PKC inhibitors, Ro 31-8220 and GF 109203X, reversed the inhibitory
      effect provoked by PMA, but failed to prevent thrombin-induced inhibition.
      Furthermore, the protein tyrosine phosphatase inhibitor, sodium orthovanadate,
      induced dose-dependent inhibition of LTC4 production in platelet sonicates. In
      conclusion, receptor-mediated activation of human platelets leads to decreased
      LTC4 synthase activity via phosphoregulation. Although the present results
      demonstrate that platelet LTC4 synthase can be regulated via PKC-dependent
      events, alternative mechanisms appears to be involved in the physiological
      regulation of this enzyme. The findings suggest the possible importance of
      protein tyrosine phosphorylations in this process.

PMID- 8536698
TI  - Ligand specificity of pheromone-binding proteins of the processionary moth.
AB  - Photoaffinity labeling of proteins extracted from sensory hairs and antennal
      branches of the processionary moth Thaumetopoea pityocampa with a tritium-labeled
      diazoacetate analogue of the sex pheromone (Z)-13-hexadecen-11-ynyl acetate
      revealed a 15-kDa pheromone-binding protein in male moth sensory hairs (SH-15). A
      different 15-kDa protein in male antennal branches (B-15) was not photolabeled.
      All extracts except male sensory hairs showed a photolabeled 20-kDa protein; a
      photolabeled male 30-kDa protein in the branches (B-30) was also observed. The 20
      kDa proteins in the sensory hairs (SH-20) and branches (B-20) showed differing
      affinities for the photoaffinity analogues; moreover, SH-15 exhibits higher
      affinity for the natural pheromone, (Z)-13-hexadecen-11-ynyl acetate, than for
      its alcohol metabolite and other analogues in competitive displacement
      experiments. The affinity shown by the pheromone-binding protein for the
      metabolic product suggests that the alcohol may be also transported by the
      binding protein. Interestingly, a shift in labeling from SH-15 to SH-20 was
      produced in the presence of an excess of the natural pheromone, its alcohol and
      other analogues. The binding showed little discrimination among structurally
      similar analogues of the pheromone, while saturated and aromatic molecules showed
      little affinity for the proteins of either sensory hairs or antennal branches.

PMID- 8536699
TI  - A short isoform of carcinoembryonic-antigen-related rat liver cell-cell adhesion
      molecule (C-CAM/gp110) mediates intercellular adhesion. Sequencing and
      recombinant functional analysis.
AB  - Rat liver cell-cell adhesion molecule (C-CAM) is a type I transmembrane
      glycoprotein belonging to the immunoglobulin (Ig)-superfamily. Within this family
      it is related to the carcinoembryonic antigen (CEA) proteins. C-CAM, previously
      known as gp110, cell-CAM 105, HA4/pp120 or ecto-ATPase, is a highly glycosylated
      protein with an apparent M(r) or 100,000-115,000 and an isoelectric point of 3
      3.5. It was analysed as a molecule that stimulates reaggregation of isolated
      hepatocytes. So far three different isoforms have been cloned. Only the isoform
      with a long intracellular tail (71 amino acids), C-CAM1, was shown to be involved
      in intercellular adhesion. C-CAM2, an isoform with only 10 cytoplasmic amino
      acids and a slightly different N-terminal Ig-like loop did not function as an
      adhesion molecule. In this study we show the existence of another short C-CAM
      isoform (C-CAM2a), which is an alternatively spliced product of the C-CAM1 gene.
      Like C-CAM2, it has a short cytoplasmic tail, but in the extracellular region it
      is identical to C-CAM1. To investigate whether C-CAM2a can function as an
      adhesion molecule, we stably expressed the corresponding cDNA in Chinese hamster
      ovary (CHO) cells. In these cells, we detected a specific increase of
      intercellular adhesion, indicating that, in contrast to the other short isoform,
      C-CAM2a can induce adhesion. This adhesion is homophilic and Ca2+ independent.

PMID- 8536700
TI  - The role of membrane proximal threonine residues conserved among guanine
      nucleotide-binding-protein-coupled receptors in internalization of the m4
      muscarinic acetylcholine receptor.
AB  - Many guanine-nucleotide-binding-protein-coupled receptors contain consensus
      sequences for phosphorylation by cAMP-dependent protein kinase (PKA), often
      located in the membrane proximal regions critically important for receptor
      signalling. In the present study, we have evaluated by site-directed mutagenesis
      the role of the putative PKA phosphorylation sites in the m4 muscarinic
      acetylcholine receptor (mAChR), i.e. Thr145 in the second cytoplasmic loop and
      Thr399 in the third cytoplasmic loop, and the influence of PKA on m4 mAChR
      function and internalization. Antagonist binding was unaltered by any of the
      mutations studied, while the agonist-binding affinity was either not affected
      (Thr145 alanine), increased (Thr399 alanine) or decreased (Thr399 serine or
      aspartic acid). m4 mAChR-mediated inhibition of adenylyl cyclase was unaltered by
      the mutations, except for an approximately tenfold reduced agonist potency of the
      Thr399 aspartic acid mutated receptor. Agonist-induced receptor internalization
      was unaltered with Thr399 serine or aspartic acid mutations of the receptors, but
      was strongly decreased in its rate and extent upon replacement of Thr399, Thr145
      or both of these residues with alanine. These mutational effects could not be
      reproduced by treatment of wild-type receptor-expressing cells with the PKA
      inhibitor H-8. Furthermore, maximal stimulation of cellular PKA neither affected
      receptor internalization nor signalling measured as receptor-mediated Ca2+
      mobilization. We conclude that the membrane proximal threonine residues of the m4
      mAChR are not required for receptor signalling, but replacement by alanine
      residues can significantly affect receptor internalization, independently of PKA
      phosphorylation. Sequence comparisons suggest that threonine residues at
      corresponding positions may be relevant to internalization of other guanine
      nucleotide-binding-protein-coupled receptors.

PMID- 8536701
TI  - Characterization of the human alpha 1(VI) collagen promoter and its comparison
      with human alpha 2(VI) promoters.
AB  - From a human cosmid library, we isolated a clone (5B) with an insert of 32 kb,
      encoding the amino-terminal and the 5'-end flanking region of the alpha 1(VI)
      collagen gene. Exon 1 was found to be 194 bp and contain the 5' untranslated
      region plus 97 bp coding sequence. Exon 2 consists of 130 bp, a size that is
      conserved across the chicken and mouse species. S1-nuclease-protection assays and
      primer-extension analysis, using mRNA from human dermal fibroblasts, show the
      presence of multiple transcription start sites located in a region of
      approximately 20 nucleotides. Canonical TATA and CAAT boxes, as found in the
      chicken and mouse alpha 1 promoters, were absent in the human alpha 1(VI)
      promoter. The promoter region from positions -1 to -190, is a
      polypyrimidine/polypurine-rich region containing 12 CCCTCCCC (CT element
      consensus) sequences and has multiple potential binding sites for the Sp1, and
      AP2 transcription factors. These regulatory proteins bind to the alpha 2(VI)
      promoters [Saitta, B. & Chu, M.-L. (1994) Eur. J. Biochem. 223, 675-682]. To test
      the transcriptional activity of the alpha 1 promoter, transient transfection
      experiments of the DNA constructs were performed in human dermal fibroblasts and
      in human fibrosarcoma (HT1080) cell lines. The DNA constructs drive the
      expression of the chloramphenicol acetyl transferase (CAT) gene. The results show
      strong CAT activity for the constructs at positions -1700, -298 and -257, while
      low activity was found for the constructs at positions -4400, -142 and -5 when
      transfected in fibroblasts. The experiments also identified positive and negative
      regulatory regions in the alpha 1(VI) promoter CAT constructs when transfected in
      fibroblasts, but did not identify them in the fibrosarcoma cells.

PMID- 8536702
TI  - Phosphorylation of elongation factor 1 (EF-1) by protein kinase C stimulates
      GDP/GTP-exchange activity.
AB  - Phosphorylation of the alpha, beta and delta subunits of elongation factor (EF) 1
      by protein kinase C results in stimulation of elongation activity up to threefold
      both in vivo and in vitro [Venema, R. C., Peters, H. I. & Traugh, J. A. (1991) J.
      Biol. Chem. 266, 11,993-11,998, Venema, R. C., Peters, H. I. & Traugh, J. A.
      (1991) J. Biol. Chem. 266, 12,574-12,580]. The alpha subunit catalyzes the GTP
      dependent binding of amino-acyl-tRNA to the ribosome, while the beta gamma and
      delta subunits of EF-1 catalyze exchange of the residual GDP on EF-1 alpha for
      GTP. To determine whether the change in elongation rate following phosphorylation
      by protein kinase C is due to stimulation of GDP/GTP exchange activity, EF-1 and
      EF-1.valyl-tRNA-synthetase have been purified from rabbit reticulocytes,
      phosphorylated in vitro by protein kinase C and the effect of phosphorylation on
      nucleotide-exchange activity analyzed. The alpha, beta and delta subunits are
      phosphorylated only on serine, and phosphopeptide maps show distinct
      phosphopeptides for each subunit. Following quantitative phosphorylation of EF-1
      by protein kinase C on the alpha, beta, and delta subunits, a twofold enhancement
      of the rate of nucleotide exchange over the non-phosphorylated controls is
      observed with EF-1 and EF-1.valyl-tRNA synthetase. Stimulation of nucleotide
      exchange results in a two-fold increase in the formation of EF-1 alpha.GTP.Phe
      tRNA, leading to an increased rate of binding of Phe-tRNA to ribosomes. The
      magnitude of stimulation of the exchange rate is similar to that reported
      previously for the rate of elongation following phosphorylation of EF-1 by
      protein kinase C. Thus, the enhancement of EF-1 activity in response to 4 beta
      phorbol 12-myristate 13-acetate appears to be due to stimulation of the rate of
      GDP/GTP exchange following phosphorylation of EF-1 by protein kinase C.

PMID- 8536703
TI  - Cell-density-dependent modulation of the rat insulin-like-growth-factor-binding
      protein 2 and its gene.
AB  - The steady-state level of the rat insulin-like-growth-factor-binding protein 2
      (IGFBP-2) and insulin-like-growth-factor-II (IGF-II) mRNA increased approximately
      20-fold when BRL-3A cells were cultured at increasingly higher cell densities.
      This increase could not be accounted for by paracrine or autocrine factors, or by
      the addition of insulin, IGF-I, transforming growth factor beta (TGF-beta), cAMP
      or IGFBP-2 to the culture medium. A reporter gene assay carrying the promoter
      domain of the IGFBP-2 gene indicated that the promoter-dependent IGFBP-2
      transcription is tenfold higher in high-density cells. The increase in the IGFBP
      2 message was accompanied by an increase in the level of protein in the medium.
      When confluent BRL-3A cells were reseeded at low cell density, the IGFBP-2 mRNA
      disappeared at a rate significantly faster than in normal conditions. A protein
      synthesis inhibitor, cycloheximide, was able to prevent the decay of the message
      observed after the switch from high to low densities. In summary, these findings
      suggest a regulatory link between cell density and IGFBP-2.

PMID- 8536704
TI  - Crystal structure of the transthyretin--retinoic-acid complex.
AB  - Retinoids are quite insoluble and chemically unstable compounds in the aqueous
      medium, such that natural retinoids need to be bound to specific retinoid-binding
      proteins to be protected, solubilized and transported in body fluids. All-trans
      retinoic acid exhibits a relatively high affinity for thyroxine-binding
      transthyretin in vitro and this protein is a good candidate for the transport of
      retinoic acid administered as pharmacological or antitumor agent. To define
      structural features essential for the recognition by transthyretin of a ligand
      which is structurally unrelated to thyroxine, we have cocrystallized human
      transthyretin with retinoic acid and determined its structure at 0.18-nm
      resolution. The retinoid fits into the two chemically identical thyroxine-binding
      sites, which are located in the central channel that runs through the tetrameric
      transthyretin. The cyclohexene ring of the bound retinoid is innermost, occupying
      the same position of the phenolic ring of the bound 3,3'-diiodo-L-thyronine,
      whereas the carboxylate group, like the same group of the thyroid hormone,
      participates in an ionic interaction with the Lys15 side chain at the entrance of
      the channel. Despite the fact that transthyretin was cocrystallized with all
      trans-retinoic acid, the isoprene chain of the bound retinoid has been found in a
      non-extended conformation. This feature, that allows the carboxylate to orient in
      a manner suitable for ion-pair association with the Lys15 side chain, is
      attributable to the conversion of all-trans-retinoic acid into cis-isomers or
      folded conformers. It is concluded that the presence, in an essentially
      hydrophobic molecular core of the appropriate size, of a negatively charged group
      at the correct position is a crucial requirement for ligand-transthyretin
      recognition. Whereas the binding of the ligand has no remarkable consequences for
      the protein structure, all-trans-retinoic acid undergoes structural changes such
      as to interact favorably with residues present in the thyroxine-binding sites,
      resembling roughly the natural ligand.

PMID- 8536705
TI  - Effects of pH and KCl on the conformations of creatine kinase from rabbit muscle.
      Infrared, circular dichroic and fluorescence studies.
AB  - The activity loss of creatine kinase (CK), observed at low pH (midpoint was 4.8)
      corresponded to the monomerization of the dimeric protein and was correlated with
      structural changes. The acid-induced unfolding was not complete at this pH, as
      probed by circular dichroic (CD) and fluorescence methods. Further decrease of
      pH, led to a second transition (midpoint was pH 3.5). The loss of activity was
      irreversible at pH 4.8 (< 20% native activity was recovered) while it was almost
      fully reversible (> 90% of native activity was recovered) for the enzyme
      incubated at pH 0.9-2.5. The amount of intermolecular beta-sheets (monitored with
      the 1620 cm-1 infrared component band) was maximal when the enzyme was incubated
      at pH 4.8, as a consequence of protein aggregation, while it was minimal at
      extremes of pH and at low ionic strength. Acid-induced and alkaline-induced
      denaturations promoted different structural changes, leading to distinct
      partially unfolded conformational states. The addition of KCl (from 0.05 M to 0.5
      M) to an acidic solution of monomeric creatine kinase (pH 1.6) resulted in a
      highly cooperative transition from the partially unfolded conformation (UA) to
      the more compact conformation (A) with the properties of a molten globule, as
      probed by CD spectra and by fluorescence. The formation of intermolecular beta
      sheets in the compact conformation was observed by infrared spectroscopy,
      indicating formation of unstable aggregates.

PMID- 8536706
TI  - Muscarinic toxins from the black mamba Dendroaspis polylepis.
AB  - Three new toxins acting on muscarinic receptors were isolated from the venom of
      the black mamba Dendroaspis polylepis. They were called muscarinic toxins alpha,
      beta, and gamma (MT alpha, MT beta, and MT gamma). All of the toxins have four
      disulphide bonds and 65 or 66 amino acids. The sequences of MT alpha and MT beta
      were determined. The muscarinic toxins, of which about 12 have been isolated from
      venoms of green and black mambas, have 60-98% sequence identity with each other,
      and are similar to many (about 180) other snake venom components, such as alpha
      neurotoxins, cardiotoxins, and fasciculins. In contrast to the alpha-neurotoxins,
      muscarinic toxins do not bind to nicotinic acetylcholine receptors. The binding
      constants of MT alpha and MT beta were determined for human muscarinic receptors
      of subtypes m1-m5 stably expressed in Chinese hamster ovary cells. The toxins are
      less selective than the earlier discovered muscarinic toxins from the green mamba
      Dendroaspis angusticeps. MT alpha and the muscarinic toxin MT4 from D.
      angusticeps differ only in a region of three amino acids (residues 31-33), which
      are Leu-Asn-His in MT alpha and Ile-Val-Pro in MT4. This difference causes a
      pronounced shift in subtype selectivity. MT alpha has high affinity to all
      subtypes, with Ki (inhibition constant) values of 23 nM (m1; pKi = 7.64 +/-
      0.10), 44 nM (m2; pKi = 7.36 +/- 0.06), 3 nM (m3; pKi = 8.46 +/- 0.14), 5 nM (m4;
      pKi = 8.32 +/- 0.07), and 8 nM (m5; pKi = 8.09 +/- 0.07). MT4 has high affinity
      only to m1 (Ki = 62 nM) and m4 (87 nM) receptors, and low (Ki > 1 microM)
      affinity to m2, m3, and m5. The region at positions 31-33 evidently plays an
      important role in the toxin-receptor interaction. MT beta has low affinity for m1
      and m2 receptors (Ki > 1 microM) and intermediate affinity for m3 (140 nM; pKi =
      6.85 +/- 0.03), m4 (120 nM; pKi = 6.90 +/- 0.06), and m5 (350 nM; pKi = 6.46 +/-
      0.01). The low affinity of MT beta may reflect a tendency for spontaneous
      inactivation.

PMID- 8536707
TI  - Characterization of apolipoproteins B-100, AI and C from plasma lipoprotein in
      the goose, Anser anser. Evidence for a genetic polymorphism in ApoC-like
      apolipoproteins.
AB  - In this study we have characterized four of the principle goose apolipoproteins
      and compared their physicochemical properties with human and avian counterparts.
      Goose ApoB-100 and ApoAI amino acid compositions were very similar to their
      chicken and human homologous proteins. The partial N-terminal sequence from goose
      ApoAI was 91% and 82% similar to the corresponding duck and chicken proteins,
      respectively. Most of the observed amino acid changes detected between the ApoAI
      sequences were amino acid replacements having the same characteristics and could
      be the result of a single base mutation. The N-terminal portion of two ApoC-like
      apolipoproteins were also studied. Goose ApoCa had an electrophoretic mobility of
      0.31 and exhibited a nine-residue motif that was well conserved between ApoCIII
      sequences from different species. We therefore suggest that ApoCa is the
      equivalent of mammalian ApoCIII. The N-terminal portion of goose ApoCb, the
      second major ApoC in high-density apolipoprotein, showed no similarity to
      proteins previously described in the literature. This protein displayed two
      isomorphs in alkaline urea gel electrophoresis called ApoCb1 and ApoCb2 with Rf
      values of 0.36 and 0.39, respectively. A genetic polymorphism was detected in the
      population whereby 25% of the animals carried only one isomorph and 50% exhibited
      both ApoCb isomorphs. These frequencies were similar in females and males. The
      transmission mode of these ApoCb isomorphs was consistent with two segregating
      alleles from a single codominantly expressed gene.

PMID- 8536708
TI  - Purification and properties of coenzyme F390 hydrolase from Methanobacterium
      thermoautotrophicum (strain Marburg).
AB  - 8-Hydroxyadenylylated coenzyme F420 (coenzyme F390-A) is formed in methanogenic
      bacteria upon oxidative stress. After reinstatement of anaerobic conditions,
      coenzyme F390 is degraded into coenzyme F420 and AMP. The enzyme catalyzing the
      latter reaction, coenzyme F390 hydrolase, was purified to homogeneity from
      Methanobacterium thermoautotrophicum strain Marburg 355-fold to a specific
      activity of 12.1 mumol.min-1.mg protein-1. The enzyme consisted of one
      polypeptide of approximately 27 kDa. Coenzyme F390 hydrolase displayed an
      apparent Km for coenzyme F390 of 40 microM. The enzyme required the presence of a
      reducing agent like dithiothreitol to become active. Activity could be
      manipulated by applying various ratios of reduced and oxidized dithiothreitol.
      Activation proceeded by a two-electron reduction, which indicates that one S-S
      bridge is involved the activation/inactivation of the enzyme. Dithiothreitol
      could be replaced by the methanogenic C1-carrier 2-mercaptoethanesulfonate (H-S
      CoM), but not by N7-mercaptoheptanoyl-L-threonine phosphate (H-S-HTP) or other
      naturally occurring thiol-containing compounds. The addition of the
      heterodisulfide of H-S-CoM and H-S-HTP (CoM-S-S-HTP) diminished the stimulatory
      effect of H-S-CoM.

PMID- 8536709
TI  - Production of recombinant human brain type I inositol-1,4,5-trisphosphate 5
      phosphatase in Escherichia coli. Lack of phosphorylation by protein kinase C.
AB  - The dephosphorylation of inositol 1,4,5-trisphosphate (InsP3) to inositol 1,4
      bisphosphate is catalyzed by InsP3 5-phosphatase. The coding region of human
      brain type I InsP3 5-phosphatase was expressed as a fusion protein with the
      maltose-binding protein (MBP) in Escherichia coli, using the pMAL-cR1 vector. The
      relative molecular mass of the purified fusion protein (MBP-InsP3-5-phosphatase)
      was approximately M(r) 85,000 as analysed by SDS/PAGE. The yield was about 10 mg
      fusion protein/l lysate. After cleavage from MBP with factor Xa, the specific
      activity of recombinant 5-phosphatase was 120-250 mumol.mg-1.min-1. The molecular
      mass of purified protein by SDS/PAGE was M(r) 43,000. The activity was
      inactivated by p-hydroxymercuribenzoate. The possibility that protein kinase C
      might phosphorylate InsP3 5-phosphatase was tested on the purified 43,000 M(r)
      protein. In this study, we show that recombinant 5-phosphatase is not a substrate
      of protein kinase C.

PMID- 8536710
TI  - The mechanism of substrate and coenzyme binding to clostridial glutamate
      dehydrogenase during reductive amination.
AB  - The binding of NADH and 2-oxoglutarate to glutamate dehydrogenase (GDH) from
      Clostridium symbiosum has been studied by fluorescence spectroscopy. The Kd
      values for the binding of these ligands have been measured by titration of either
      the nucleotide or protein fluorescence. During ternary complex formation, the
      substrate and coenzyme binding sites interact in a positive cooperative manner,
      but steady-state studies reveal a decrease in affinity of the catalytic complex
      indicative of negative cooperativity. It was possible to determine the kinetics
      of formation of the glutamate-dehydrogenase-NADH complex by stopped-flow
      fluorescence spectroscopy but formation of the glutamate-dehydrogenase-2
      oxoglutarate complex was optically silent. Ternary complex formation was
      characterized by a large quench in protein fluorescence. The binding of NADH to
      the glutamate-dehydrogenase-2-oxoglutarate binary complex is characterised by a
      linear increase in the association rate constant, consistent with a one-step
      binding process. However, the binding of 2-oxoglutarate to the glutamate
      dehydrogenase-NADH binary complex is characterised by a decrease in the rate for
      the observed transient. This suggests that 2-oxoglutarate binds to a different
      conformation of the enzyme to that stabilized by NADH, and that the transition
      between these different conformational forms is rate limiting for ternary complex
      formation. NADH and 2-oxoglutarate can therefore stabilize different
      conformational states of the enzyme. Collectively, these studies are suggestive
      of a kinetic model for ternary complex formation that involves the oscillation of
      the free, binary, and ternary glutamate dehydrogenase complexes between two
      different conformational states, termed E1 and E2. The equilibrium constants for
      ternary complex formation via the predominant pathway have been determined. The
      cooperativity between the substrate and coenzyme binding sites can be accounted
      for by the displacement of the equilibria between the E1 and E2 states because of
      their difference in affinities for NADH and 2-oxoglutarate.

PMID- 8536711
TI  - Synthesis of a divalent sialyl Lewis x O-glycan, a potent inhibitor of lymphocyte
      endothelium adhesion. Evidence that multivalency enhances the saccharide binding
      to L-selectin.
AB  - The recognition of cell-surface L-selectin by its carbohydrate ligands causes
      lymphocytes to roll on capillary endothelium at sites of inflammation. As this
      primary contact is a prerequisite for extravasation of the leukocytes to the
      tissue, its inhibition by free oligosaccharides capable of competing with the
      natural L-selectin ligands in an attractive therapeutic possibility. The exact
      structures of the biological ligands of L-selectin are not yet known, but the
      principal carbohydrate epitopes share some structural features: they are O
      glycosidically linked mucin-type oligosaccharides with N-acetyllactosamine
      backbone, which is 3'-sialylated or 3'-sulfated, 3-fucosylated and sometimes 6-
      or 6'-sulfated at the distal N-acetyllactosamine termini. Multivalency of the
      ligand, which is believed to enhance the binding, is achieved by a branched
      polylactosamine backbone or by a clustered array of O-glycans. We report here
      enzymic synthesis of a large oligosaccharide fulfilling several of the features
      characteristic to the L-selectin ligands: it is a dodecameric O-glycosidic core-2
      type oligosaccharide alditol with a branched polylactosamine backbone carrying
      two distal alpha-2,3'-sialylated and alpha-1,3-fucosylated N-acetyl-lactosamine
      groups (sialyl Lewis x, sialyl Le(x)). The structure of each saccharide on the
      synthesis route from disaccharide Gal beta 1-3GalNAc to the dodecasaccharide
      alditol was established by several methods including one- and two-dimensional 1H
      NMR spectroscopy. The last step of the synthesis, the alpha-1,3-fucosylation of
      the 6-linked arm proceeded sluggishly, and was associated with a noticeable shift
      in H1 resonance of the GlcNAc residue of the branch-bearing N-acetyllactosamine
      unit. The final synthesis product and its analogs lacking one or both of the
      fucose residues were tested as inhibitors of L-selectin-mediated lymphocyte
      endothelium interaction in vitro in rejecting rat kidney transplant. While the
      non-fucosylated O-glycosidic oligosaccharide alditol did not possess any
      inhibitory activity, the mono-fucosylated one (i.e. monovalent sialyl Le(x))
      prevented the binding significantly and the difucosylated dodecasaccharide
      alditol (i.e. divalent sialyl Le(x)) was a very potent inhibitor (IC50,
      inhibitory concentration preventing 50% of binding = 0.15 microM). Besides the
      multivalency, also the Gal beta 1-3GalNAc-ol sequence of the O-glycosidic core
      appeared to increase the affinity of the glycan to L-selectin. This was indicated
      by parallel inhibition experiments, where a disialylated and difucosylated
      branched polylactosamine decasaccharide, similar to the divalent dodecasaccharide
      alditol, but lacking the reduced O-glycosidic core, was a less effective
      inhibitor (IC50 = 0.5 microM) than the O-glycosidic dodecasaccharide alditol.

PMID- 8536712
TI  - Effect of the aminosteroid, U73122, on Ca2+ uptake and release properties of rat
      liver microsomes.
AB  - The putative phospholipase C inhibitor, U73122, transiently increases the
      cytosolic free Ca2+ concentration in rabbit pancreatic acinar cells by
      stimulating the release of Ca2+ from intracellular stores [Willems, Van de Put,
      Engbersen, Bosch, Van Hoof & De Pont (1994) Pflugers Arch. 427, 233-243]. In
      order to elucidate the exact mechanism of action of U73122 we studied its effects
      on both Ca(2+)-stimulated Mg(2+)-dependent ATPase activity and Ca(2+)-stimulated
      ATP-dependent Ca2+ uptake in rat liver microsomes. In addition, we studied its
      effects on Ca2+ release from steady-state loaded microsomes. The effects of
      U73122 were compared with those of thimerosal, described in the literature as
      inhibiting Ca(2+)-ATPases and sensitizing inositol 1,4,5-trisphosphate-operated
      Ca2+ release channels, and thapsigargin, a specific inhibitor of sarcoplasmic and
      endoplasmic reticulum Ca(2+)-ATPases. Both U73122 (IC50 = 9 microM) and
      thimerosal (IC50 = 11 microM) dose-dependently inhibited Ca(2+)-stimulated Mg(2+)
      dependent ATPase activity, without significantly affecting Mg(2+)-stimulated
      ATPase activity. Similarly, both U73122 (IC50 = 9 microM) and thimerosal (IC50 =
      14 microM) dose-dependently inhibited ATP-dependent Ca2+ uptake. At
      concentrations beyond 20 microM, U73122 stimulated Ca2+ release from steady-state
      loaded microsomes at a rate considerably higher than obtained with a maximally
      inhibitory concentration of thapsigargin (1 microM). This observation, which was
      not reached with equally inhibitory concentrations of thimerosal, demonstrates
      that higher U73122 concentrations cause an additional increase of passive Ca2+
      leak. The data presented demonstrate that U73122 stimulates the release of
      actively stored Ca2+ primarily through inhibition of the internal Ca2+ pump.

PMID- 8536713
TI  - The genomic response of tumor cells to hypoxia and reoxygenation. Differential
      activation of transcription factors AP-1 and NF-kappa B.
AB  - Hypoxia and reoxygenation are important pathophysiological conditions that occur
      during injury, ischemia, reperfusion and stroke. In tumors, hypoxia and oxidative
      stress are regarded as triggers for enhanced proliferation and metastasis.
      Hypoxia and reoxygenation exert part of their biological effects by inducing the
      expression of novel genes but very little is known about the transcription
      factors involved. Here, we have compared the behaviour of two redox-controlled
      factors, AP-1 and NF-kappa B, during hypoxia and reoxygenation. We report that
      the DNA-binding and transcriptional activity of transcription factor AP-1 is very
      strongly induced in a biphasic response when HeLa cells are exposed to reduced
      oxygen pressure. This induction required new AP-1 protein synthesis. Different
      members of the Jun/Fos family of transcription factors were found in the first
      and second maxima of activation. The pathogen-responsive, pre-existing
      transcription factor NF-kappa B was not activated under hypoxic conditions.
      However, a p50-p65 heterodimer of NF-kappa B was rapidly and strongly activated
      when HeLa cells were re-exposed to normal oxygen pressure. This explains the
      induction of NF-kappa B-controlled inflammatory cytokine genes during reperfusion
      of ischemic tissue. Our data suggest that the genomic response to hypoxia is
      primarily mediated by AP-1 while the inflammatory response to reoxygenation is
      mediated by NF-kappa B.

PMID- 8536714
TI  - Complexes of tissue kallikrein with protein C inhibitor in human semen and urine.
AB  - An ELISA was developed for quantifying the complex between tissue kallikrein
      (tKK) and protein C inhibitor (PCI) (tKK:PCI) in seminal plasma and urine. The
      ELISA used purified tKK:PCI complex as a standard and was specific for this
      complex with a detection limit of about 1.1 pM. Purified tKK:PCI complex was
      obtained from human urine and was 95% homogeneous as judged by SDS/PAGE. The 90
      kDa band corresponding to the purified tKK:PCI complex reacted with anti-tKK and
      anti-PCI antibodies as judged by immunoblotting. Seminal plasma collected in the
      absence of extrinsic inhibitors contained 1.8 +/- 0.6 nM tKK:PCI complex and 4.7
      +/- 2.8 nM immunoreactive tKK (mean +/- SD, n = 10), which indicates that about
      28% of the total tKK immunoreactivity is forming complexes with PCI. When semen
      was collected in the presence of tKK inhibitors it had only about 6% of the tKK
      complexed to PCI. In vitro studies showed that the tKK:PCI complex formation in
      semen was accomplished in about 1 h and that heparin stimulated both the rate and
      the extent of complexation of tKK with PCI. Native urine showed low levels of
      tKK:PCI complex, but after dialysis urine had 0.17 +/- 0.05 nM complex. Formation
      of tKK:PCI complex in urine and semen was also demonstrated by immunoblotting.
      These results suggest that PCI is a physiological inhibitor of tKK and provide
      additional evidence of the involvement of PCI in human reproduction.

PMID- 8536715
TI  - The replacement of Trp392 by alanine influences the decarboxylase/carboligase
      activity and stability of pyruvate decarboxylase from Zymomonas mobilis.
AB  - The bulky tryptophan residue 392 located in the deep cleft leading to the active
      center of pyruvate decarboxylase (PDC) from Zymomonas mobilis was changed to
      alanine which is found in the equivalent position of PDC from yeast. The mutation
      reduced the decarboxylase activity towards pyruvate by a factor of two (60-70
      U/mg), whereas the Km (1.1 mM in Mes/KOH buffer) remains unchanged compared with
      the wild-type enzyme. The apparent Km for thiamine diphosphate (thiamin-P2) in
      the presence of 5 mM MgSO4 was increased by a factor of 10 (84 microM in Mes/KOH
      buffer) and the tetrameric mutant protein was less stable, as indicated by urea
      denaturation experiments. The mutation enhanced the carboligase activity of the
      enzyme towards benzaldehyde by a factor of four. The resulting alpha
      hydroxyketone was identified as (R)-phenylacetylcarbinol.

PMID- 8536716
TI  - Involvement of Janus kinases in the insulin signaling pathway.
AB  - The adaptor molecule growth-factor-receptor-bound protein-2 (Grb2) plays a role
      in insulin action since it links tyrosine phosphorylated IRS-1 and Shc to the
      guanine-nucleotide-exchange factor, Sos, which initiates the mitogen-activated
      protein (MAP) kinase cascade by producing Ras-GTP. Both IRS-1 and Shc are
      phosphorylated by the insulin-receptor tyrosine kinase. In the present study, we
      have investigated whether the tyrosine kinases of the Janus kinase family (JAK)
      could be involved in insulin signaling by acting on Grb2. In fibroblasts over
      expressing insulin receptors we observed that two tyrosine-phosphorylated
      proteins interact with Grb2 and with a mutant of Grb2, which lacks the Src
      homology 2 (SH2) domain, indicating that these proteins associate with the SH3
      domains of Grb2. Further, we found that both JAK1 and JAK2 constitutively
      associate with Grb2, through interaction with the SH3 domains of Grb2. Finally,
      insulin appears to induce the tyrosine phosphorylation of JAK1, but does not
      modify the tyrosine phosphorylation state of JAK2. In conclusion, our results
      suggest that the JAK proteins could participate in insulin signal transduction,
      and could therefore constitute an alternative pathway for mediating some of the
      pleiotropic responses induced by insulin.

PMID- 8536717
TI  - Soluble human interleukin-6 receptor. Expression in insect cells, purification
      and characterization.
AB  - The extracellular domain of the human interleukin-6 (IL-6) receptor, comprising
      339 amino acids following the signal peptide, has been expressed in baculovirus
      infected insect cells (Sf158). When the soluble receptor secreted into the
      culture medium was purified by affinity chromatography, using IL-6 immobilized on
      Sepharose, 6 mg soluble receptor was isolated from 1 l conditioned medium of
      Sf158 suspension cultures. A molar absorption coefficient of 9.3 x 10(4) l.mol
      1.cm-1 was calculated from the ultraviolet spectrum of the soluble IL-6 receptor.
      After SDS/PAGE and silver staining, an apparent molecular mass of 48 kDa was
      estimated for the purified protein. Deglycosylation with peptide N-glycosidase F
      resulted in an increase in electrophoretic mobility and a decrease in the
      apparent molecular mass from 48 kDa to about 41-44 kDa. As expected, the soluble
      human IL-6 receptor bound human 125I-labeled IL-6 with low affinity (Kd = 500
      pM). Furthermore, the binding of soluble human IL-6 receptor to immobilized IL-6
      was studied using real-time interaction analysis. The recombinant soluble
      receptor showed biological activity on HepG2 cells stably transfected with a cDNA
      coding for IL-6 (HepG2-IL-6 cells). Haptoglobin mRNA synthesis was induced by the
      soluble IL-6 receptor at concentrations as low as 10 ng/ml. Five monoclonal
      antibodies were generated. Two groups of antibodies were identified mapping to
      amino acids 1-67 and 68-143 of the soluble IL-6 receptor, respectively. The
      plasma clearance of soluble 125I-labeled IL-6 receptor in the absence and
      presence of IL-6 was studied in rats as a model system. The kinetics was
      biphasic. Soluble IL-6 receptor/IL-6 complexes were cleared more rapidly than the
      soluble receptor alone. Intravenously injected soluble 125I-labeled IL-6
      receptor, as well as complexes with IL-6, rapidly accumulated in liver and to a
      lesser extent in skeletal muscle, skin and kidneys. Subsequently, the
      radioactivity appeared in the gut content.

PMID- 8536718
TI  - Characterization of the ovine-lens plasma-membrane protein-kinase substrates.
AB  - The cAMP-dependent protein-kinase-catalyzed phosphorylation of the two major
      intrinsic lens fiber cell plasma membrane proteins, MP20 and MP26, is likely
      restricted to the inner cortical and nuclear regions of the lens in vivo. The
      ovine-lens-specific connexin, MP70, that has been identified as Cx50 in mice and
      Cx45.6 in the chick, is also a protein kinase substrate although it does not
      appear to be phosphorylated by a number of protein kinases including cAMP
      dependent protein kinase, calmodulin-dependent protein kinase or protein kinase
      C. Rather, an extrinsic lens membrane fraction was isolated which contained
      protein kinase activity that catalyzed the phosphorylation of MP70; this protein
      kinase activity was cAMP-independent, Ca(2+)-independent, Mg(2+)-dependent,
      phosphorylated MP70 on a serine residue(s) and migrated with a molecular mass of
      35 kDa on a gel filtration column. Both MP70 phosphorylation and the endogenous
      protein kinase activity were restricted to the lens outer cortical region. This
      membrane-associated protein kinase activity represents the first reported partial
      characterization of an endogenous lens fiber cell protein kinase activity that
      catalyzes the phosphorylation of a lens connexin protein. The phosphatase-induced
      shift in the electrophoretic mobility of MP70 is not reversed by this protein
      kinase, indicating that MP70 is likely phosphorylated on different residues by
      two or more protein kinases.

PMID- 8536719
TI  - Diethylumbelliferyl phosphate inhibits steroidogenesis by interfering with a long
      lived factor acting between protein kinase A activation and induction of the
      steroidogenic acute regulatory protein (StAR).
AB  - Diethylumbelliferyl phosphate (DEUP) is an organophosphate cholesteryl ester
      hydrolase inhibitor that blocks steroidogenesis mainly by preventing cholesterol
      transport into the mitochondria of steroidogenic cells. In the present study, we
      show that DEUP blocks the cAMP-stimulated mitochondrial accumulation of the 30
      kDa mitochondrial proteins (recently named steroidogenic acute regulatory StAR
      proteins) that are believed to be the cycloheximide-sensitive factors induced by
      trophic hormones and cAMP. Inhibition of mitochondrial StAR accumulation by DEUP
      is dose dependent and closely parallels inhibition of progesterone synthesis.
      Stimulated lactate production, another cAMP-dependent process in MA-10 cells, is
      also inhibited by DEUP. Inhibition of protein kinase A (PKA) action would explain
      the inhibition of these two unrelated processes. However, the cytosolic PKA
      activity of DEUP-treated MA-10 10 cells was normal. Moreover, the activity of
      purified PKA was unaffected by DEUP. The inhibition of StAR synthesis was not
      caused by a direct effect of DEUP on the labile proteins since DEUP-treated cells
      required more than 24 h to recover steroidogenic capacity after DEUP treatment.
      Further evidence that the synthesis of StAR was not directly affected was
      obtained using the constitutively active R2C cells. Progesterone synthesis by
      these cells also involves StAR, but neither StAR synthesis or steroid synthesis
      is sensitive to DEUP. Lactate formation in dibutyryl-cAMP-stimulated R2C cells
      is, however, sensitive to inhibition by DEUP. These data can be best explained by
      DEUP acting on a long-lived factor involved in the cAMP/PKA response pathway, but
      not involved in constitutive steroidogenesis.

PMID- 8536720
TI  - Perturbation of the CuA site in cytochrome-c oxidase of Paracoccus denitrificans
      by replacement of Met227 with isoleucine.
AB  - Subunit II of cytochrome-c oxidase contains a redox centre, CuA, with unusual
      spectroscopic properties; this site consists of two copper atoms and acts as the
      entry point for electrons from cytochrome c. We have constructed a site-directed
      mutant of cytochrome-c oxidase from Paracoccus denitrificans in which the CuA
      site has been disturbed by replacement of Met227 with isoleucine. The purified,
      fully assembled enzyme complex has been investigated with various techniques
      including metal analysis, EPR and visible spectroscopies, steady-state and fast
      kinetics. The stoichiometry of the metals in the enzyme remains unchanged but a
      clear perturbation of the CuA site can be observed in the EPR and near-infrared
      optical spectra. It is concluded that in the mutant CuA is still binuclear but
      that the two nuclei are no longer equivalent, converting the delocalized
      [Cu(1.5)....Cu(1.5)] centre of the wild type into a localized [Cu(I)....Cu(II)]
      system. Changes in the overall kinetics of the mutant are correlated with a
      diminished electron transfer rate between CuA and heme alpha.

PMID- 8536721
TI  - Opportunistic fusarial infections in humans.
AB  - Fusarium species are common hyaline soil saprophytes and plant pathogens which
      have frequently been reported as etiologic agents of opportunistic infections in
      humans. These infections have usually been limited to superficial mycoses, but
      recently the number of infections of deep tissues and disseminated infections has
      greatly increased, especially in patients with an underlying immunosuppressive
      condition. The characteristic signs of these infections are disseminated skin
      nodules, fungemia and multiorgan involvement. Frequently, myalgia is also
      present. Skin involvement occurred in over 80% of cases of disseminated
      infections. These lesions are significant because they are readily accessible for
      biopsy and culture, thus permitting an early diagnosis. The therapy and outcome
      are dependent on the degree of invasion of the organisms and the status of the
      host. Identification of the pathogen to genus level is not difficult, but
      identification to species level requires a greater degree of expertise. Up to
      now, 15 species of Fusarium have been reported to cause infections in humans and
      animals. Few patients with disseminated fusarial infections have survived, even
      after receiving an adequate dosage of amphotericin B, the only antifungal agent
      that has some effect against these fungi. In vitro susceptibility to amphotericin
      B is a poor predictor of the clinical outcome of invasive fungal infections.
      Recovery of the phagocytic mechanisms in the form of rising neutrophil counts
      appears to be mandatory for clinical resolution. The resolution of neutropenia
      may be aided by the use of exogenous growth factors. Outside the USA, the
      majority of cases of disseminated fusarial infection have been reported from
      Mediterranean or tropical countries.

PMID- 8536722
TI  - Nontuberculous mycobacterial infection in HIV-negative patients receiving
      immunosuppressive therapy.
AB  - The clinical significance of nontuberculous mycobacterial isolates and
      presentation of mycobacteriosis was compared in HIV-negative patients with or
      without preceding immunosuppression. Patients with nontuberculous mycobacterial
      isolates (n = 139), mainly from the respiratory system, were divided into three
      groups: those who had had previous immunosuppressive treatment (24%), those with
      other underlying diseases (54%) and those without predisposing factors (22%). The
      distribution of mycobacterial species among the various patient groups was
      similar. The immunosuppressed patients fulfilled the criteria of the American
      Thoracic Society for clinical mycobacteriosis less frequently (18%) than those
      with other underlying diseases (32%) or without predisposing factors (45%), p =
      0.07, the difference being more striking for patients with Mycobacterium avium
      complex isolates. This was partly due to the difficulty in distinguishing the
      relevant symptoms from those caused by the underlying disease. The proportion of
      patients receiving antimycobacterial therapy differed similarly (18%, 21%, 45%,
      respectively). Among the immunosuppressed patients, positive acid-fast smears
      were significantly less common and polymicrobial infections, initial
      lymphocytopenia, fever and fatal outcome significantly more common. About half of
      the immunosuppressed patients died within one year. In order to better define
      patients requiring treatment, the criteria for localized mycobacteriosis among
      immunosuppressed patients should be reevaluated.

PMID- 8536723
TI  - Enzyme immunoassay for detection of antibodies against isolated flagella of
      Legionella pneumophila.
AB  - Flagella of Legionella pneumophila serogroup 1, strain Philadelphia (ATCC 33152),
      were isolated and used as antigen to detect antibodies by enzyme immunoassay
      (EIA) in sera of patients with significant titers against Legionella as
      determined by the indirect immunofluorescence assay (IFA). Healthy blood donors
      served as a control group. Whereas the sera of blood donors were negative in both
      assays, sera of patients showed two patterns of reactivity. Sera with elevated
      titers against Legionella pneumophila serogroup 1 or Legionella gormanii in IFA
      usually demonstrated high titers in EIA. However, high IFA titers against
      Legionella bozemanii were associated with low titers in EIA. The data show that
      flagella protein of Legionella pneumophila serogroup 1 strain Philadelphia is of
      limited value for the detection of antibodies against Legionella other than
      Legionella pneumophila serogroup 1, although in vitro studies revealed genus
      specific epitopes. This might be due to unpredictable variabilities in the
      expression of flagella in vivo.

PMID- 8536724
TI  - An autopsy study of systemic fungal infections in patients with hematologic
      malignancies.
AB  - The aim of this study was to determine the incidence of fungal infections
      detected on autopsy in a group of 40 patients with hematologic malignancies
      treated with intensive chemotherapy or bone marrow transplantation, and to
      evaluate the risk factors for fungal infections. A control group included 38
      patients with nonhematologic diseases and without granulocytopenia but with at
      least one of the known risk factors for fungal infections. Standard
      histopathological and microbiological methods were used. A higher incidence of
      invasive fungal infections was found in patients with hematologic malignancies as
      compared to the control group (p < 0.01). The predominant causes of fungal
      infections were Candida albicans and Aspergillus spp. The incidence of fungal
      infections caused by Aspergillus was higher (p < 0.05) in patients with
      hematologic malignancies than in the control group. The independent risk factors
      for fungal infections were fungal colonization, number of antibiotics and
      duration of antibiotic therapy, duration of fever and skin rash. A higher
      proportion of fungal infections was diagnosed on autopsy than during the
      patients' life (p < 0.01).

PMID- 8536725
TI  - Comparison of media for agar dilution susceptibility testing of Bordetella
      pertussis and Bordetella parapertussis.
AB  - Antimicrobial susceptibility testing of the fastidious species Bordetella
      pertussis and Bordetella parapertussis is not standardized. In an attempt to find
      the optimal medium for agar dilution testing, the activity of erythromycin
      against Bordetella pertussis and Bordetella parapertussis (34 isolates each) was
      assessed using homologous broth/agar combinations of Bordet-Gengou, charcoal, Iso
      Sensitest (Oxoid) and Mueller-Hinton media. Each medium was supplemented with 5%
      and 20% whole defibrinated horse blood. Mueller-Hinton medium supplemented with
      5% horse blood performed best overall.

PMID- 8536726
TI  - Development of a rapid PCR method for identification of Helicobacter pylori in
      dental plaque and gastric biopsy specimens.
AB  - A rapid and simple polymerase chain reaction (PCR) method was developed to detect
      Helicobacter pylori in gastric biopsy specimens and dental plaque samples. The
      primers were targeted to the 16S rRNA sequence of Helicobacter pylori strain ATCC
      43504. The system was found to have a theoretical detection level of 0.5 to 5
      Helicobacter pylori cells in a 5 microliters sample of dental plaque. In the
      absence of plaque, the detection level was even better: theoretically, 0.05 to
      0.5 Helicobacter pylori cells were detected in water suspension. However, this
      appeared to be due to the presence of free bacterial DNA in the culture used for
      the sensitivity determination. Thus, the actual sensitivity of the system was
      found to be fewer than five Helicobacter pylori cells, irrespective of the type
      of sample used. The method was then used to analyse 29 dental plaque and gastric
      biopsy specimens collected from patients with a history of recurrent peptic ulcer
      disease. Fourteen stomach specimens were positive for Helicobacter pylori when
      tested with the PCR method, while the respective figures with culture,
      histological examination and the urease test were 11, 12 and 9. No positive
      dental plaque samples were observed.

PMID- 8536727
TI  - Multicenter evaluation of a new commercial assay for detection of immunoglobulin
      M antibodies to Toxoplasma gondii. Multicenter Study Group.
AB  - A new commercial assay for detection of IgM-specific antibodies to Toxoplasma
      gondii (IMx Toxo IgM, Abbott, USA), based on microparticle enzyme immunoassay
      technology, was evaluated at 15 clinical sites in Europe and the USA. Performance
      characteristics were established by testing clinical specimens collected randomly
      from pregnant women, blood donors, individuals with suspected Toxoplasma gondii
      infection and individuals confirmed HIV positive. Reference testing was performed
      using Toxo-M EIA (Abbott). Specimens evaluated at European sites yielding
      discordant results between the new assay and the reference EIA were further
      tested with an immunosorbent agglutination assay; at sites in the USA, discordant
      results were resolved using Platelia Toxo IgM (Sanofi, France) and Vidas Toxo IgM
      (bioMerieux, France) assays. In addition, matched plasma and serum, heat-treated
      and non-heat-treated specimens, and fresh and frozen specimens were evaluated at
      the USA sites. At European sites the new commercial assay had a sensitivity of
      95.6% (196/205), a specificity of 99.8% (3,137/3,143) and an agreement of 99.6%
      (3,333/3,348) following resolution of discordant results; sensitivity in the USA
      was 97.4% (184/189), specificity was 99.8% (1,204/1,207) and agreement was 99.4%
      (1,388/1,396) following resolution. The new IMx Toxo IgM is a sensitive and
      specific assay for measurement of IgM antibodies to Toxoplasma gondii in human
      serum and plasma.

PMID- 8536729
TI  - Neonatal infection with Streptococcus milleri.
AB  - Streptococcus milleri is a known commensal of the female genitourinary tract, but
      its pathogenicity in neonates has been reported in only a few cases. During a
      period of one year in an obstetrical unit, Streptococcus milleri was isolated
      from nine neonates and from one foetus after a spontaneous abortion. In seven of
      the nine newborns, neonatal infection was assessed and Streptococcus milleri was
      the lone pathogen involved, associated with positive blood or vaginal cultures in
      four mothers. Because Streptococcus milleri requires special conditions for
      identification, it is probably underestimated as a cause of neonatal infection
      and septic abortion.

PMID- 8536728
TI  - Immunity to diphtheria in northern Norway and northwestern Russia.
AB  - A case of diphtheria, which has not been seen in Norway for 30 years, was
      reported in 1992 in the northern part of the country bordering Russia. An
      increasing number of cases of diphtheria has been reported in the former USSR,
      including the northwestern part of Russia. In order to elucidate the potential of
      an epidemic spread across the Norwegian-Russian border, a seroepidemiological
      study was performed. A total of 470 sera, 243 from Finnmark, Norway, and 227 from
      Arkhangelsk, Russia, were examined for antibodies against diphtheria toxin, using
      an in vitro toxin neutralisation method. No statistically significant difference
      in the presence of diphtheria antitoxin between the Norwegian and the Russian
      populations was found. The presence of neutralising antibodies decreased by age,
      and this decrease was most pronounced among the Russians. Individuals aged 40 to
      70 years, and Norwegian women in particular, seem to have an increased risk for
      diphtheria as judged by the diphtheria antitoxin levels.

PMID- 8536730
TI  - Bacteremia caused by Brevibacterium species in an immunocompromised patient.
AB  - A 46-year-old woman suffering from non-Hodgkin's lymphoma was admitted to the
      hospital because of high fever. Multiple blood cultures revealed an unusual
      finding, a Brevibacterium species, which was reisolated 16 days later from the
      tip of her long-term central venous catheter. This case indicates that
      Brevibacterium species isolated from normally sterile sites should be considered
      as a potential pathogen, especially in immunocompromised patients.

PMID- 8536731
TI  - Report of four cases of Yersinia pseudotuberculosis septicemia and a literature
      review.
AB  - Yersinia pseudotuberculosis is a rare cause of disease in humans, the most common
      manifestation being mesenteric lymphadenitis accompanied by abdominal pain and
      fever. A septicemic form of Yersinia pseudotuberculosis infection has been
      reported only rarely. It is usually seen in patients with underlying disorders
      such as diabetes, hepatic cirrhosis or iron overload. Fifty-four cases of
      septicemic infection were found in the literature. The earlier published cases
      are reviewed, and four cases occurring in Finland during the period February to
      June 1992 are reported.

PMID- 8536732
TI  - Efficacy of a universal screening program for the prevention of neonatal group B
      streptococcal disease.
AB  - Universal antepartum vaginal cultures for group B streptococcus (GBS) were
      initiated in a Spanish hospital in 1994 using Granada medium. Infants born to
      carriers were monitored closely, and blood, urine and mucocutaneous areas were
      cultured for GBS. Group B streptococcus was detected in 543 of 4,525 women (12%).
      Of these, 454 gave birth vaginally, of whom 201 (44%) received intrapartum
      ampicillin. Prophylaxis was not administered to 253 women (56%). In this group,
      infants of 120 women were colonized and 1 case of neonatal GBS disease occurred.
      Using this protocol, most GBS carriers with risk factors received intrapartum
      prophylaxis. This protocol also led to early identification of colonized
      newborns.

PMID- 8536733
TI  - Cutaneous mucormycosis in a heart transplant patient associated with a peripheral
      catheter.
AB  - The first known case of an intravascular catheter-related primary cutaneous
      mucormycosis in a heart transplant patient is reported. The patient had
      corticosteroid-induced hyperglycemia and experienced an acute tissue rejection
      episode. A necrotic lesion appeared around the insertion site of a peripheral
      venous catheter. A biopsy revealed typical mucorales hyphae. The lesion continued
      to spread during the following 24 hours and necessitated amputation of the
      forearm. The organism was identified as a Mucor species.

PMID- 8536734
TI  - Evaluation of a rapid agglutination test for detection of group B streptococci in
      the gastric aspirates of neonates.
AB  - A rapid commercial agglutination test (Bactigen Strepto B) for detection of group
      B streptococci in gastric aspirates of neonates was evaluated. One hundred and
      sixty-one gastric samples were analyzed with conventional bacteriological
      techniques and with the commercial test after modification of the extraction
      technique. The sensitivity of the test relative to the culture technique was
      90.4%, the specificity 94.2%, the positive predictive value 70.3% and the
      negative predictive value 98.5%. The commercial test could be performed in one
      hour and showed good sensitivity and specificity. If a test result was negative
      colonization could be excluded, obviating the need for empirical antibiotic
      therapy, whereas a positive result suggested colonization or neonatal infection
      with group B streptococci.

PMID- 8536735
TI  - Hydrolytic enzymes of Streptococcus anginosus, Streptococcus constellatus and
      Streptococcus intermedius in relation to infection.
AB  - A collection of 518 'Streptococcus milleri' strains was tested for the presence
      of hydrolytic enzymes, and the results were related to the clinical significance
      of the strains. Ribonuclease activity was equally distributed among the three
      species while hyaluronidase activity was linked to Streptococcus intermedius and
      Streptococcus constellatus. Both enzymes were not significantly associated with
      infection-related strains. Deoxyribonuclease and chondroitin sulfatase activity
      tended to be present more frequently in Streptococcus intermedius and
      Streptococcus constellatus and was associated with infection-related strains (p <
      0.001).

PMID- 8536736
TI  - Rate of detection of human herpesvirus-6 at different stages of HIV infection.
AB  - In a cross-sectional study, human herpesvirus-6 (HHV-6) infection was analysed by
      means of polymerase chain reaction in peripheral blood mononuclear cells (PBMCs)
      and saliva from 125 HIV-seropositive subjects and 29 HIV-seronegative controls.
      HHV-6 was detected in saliva significantly more frequently in HIV-seronegative
      subjects than in HIV-seropositive subjects (p = 0.023), with no significant
      difference between HIV-seropositive subgroups. The HIV proviral copy number in
      PBMCs differed significantly according to HIV subgroup, as expected, but did not
      differ according to either the presence of HHV-6 or the number of HHV-6 copies in
      PBMCs. All the HHV-6 identified were variant B except for one variant A strain
      detected in saliva from a healthy subject. These results do not support the
      hypothesis that there is synergistic activation of HHV-6 infection in the course
      of HIV infection.

PMID- 8536737
TI  - Isolation of Mycoplasma pneumoniae from pericardial tissue.

PMID- 8536738
TI  - Cryptococcal meningitis following fludarabine treatment for chronic lymphocytic
      leukemia.

PMID- 8536739
TI  - An imported fatal case of diphtheria in Italy.

PMID- 8536740
TI  - Current assessment of osteoporosis: proceedings of an international symposium
      convened during ECR '95 in Vienna, Austria.

PMID- 8536741
TI  - Social and economic impact of osteoporosis. A review of the literature.

PMID- 8536742
TI  - Standardization of bone mineral density measurements and the European multicentre
      studies.

PMID- 8536743
TI  - Quantitative computed tomography (QCT) of the lumbar spine and appendicular
      skeleton.

PMID- 8536744
TI  - Recent developments in DXA. Quality of new DXA/MXA-devices for densitometry and
      morphometry.
AB  - The introduction of new devices demands the assessment of their capabilities in
      established terms. The accuracy, reproducibility and spatial resolution of in
      vitro (phantom) osteodensitometric and morphometric measurements of QDR 2000 Plus
      and EXPERT are presented. Design details of these DXA/MXA-devices are listed and
      discussed in combination with the data acquired in the test measurements and
      calculations. The image quality will improve with further software developments.
      The long-term reproducibility and in vivo reliability remains to be evaluated.

PMID- 8536745
TI  - Quantitative computed tomography (QCT) and dual X-ray absorptiometry (DXA) in the
      diagnosis of osteoporosis.

PMID- 8536746
TI  - Quantitative ultrasound.

PMID- 8536747
TI  - Magnetic resonance imaging in osteoporosis.

PMID- 8536748
TI  - Standardization of postero-anterior spine bone mineral density measurements.
      Committee for Standards in DXA.

PMID- 8536749
TI  - Colour Doppler flow imaging ultrasonography versus venography as screening method
      for asymptomatic postoperative deep venous thrombosis.
AB  - OBJECTIVE: To evaluate colour Doppler flow imaging ultrasonography (CDFI),
      compared with venography, as a screening method for postoperative deep venous
      thrombosis (DVT) in a clinical trial on thromboprophylaxis. METHODS: Patients
      undergoing major abdominal or thoracic surgery were prospectively screened for
      DVT by CDFI. Patients were examined preoperatively, and on post-operative days 1,
      3, 7, 14, 21, and 28. When the CDFI was positive venography was performed.
      Bilateral venography was performed on day 28 in all patients. The study group
      comprised 82 patients who underwent CDFI and venography on the same day: four
      because of suspected DVT (positive CDFI), and 78 on day 28 according to protocol.
      RESULTS: DVT was detected by venography in seven patients, in three of whom CDFI
      was positive. CDFI was falsely positive in one case. There were two popliteal and
      five calf DVTs, of which CDFI detected one and two, respectively. The sensitivity
      of CDFI was 43%, the specificity 99%. The PVpos for CDFI was 75%, and the PVneg
      96%. CONCLUSION: Due to low sensitivity, CDFI cannot stand alone as a screening
      method for asymptomatic postoperative DVT.

PMID- 8536750
TI  - Doppler sonography: a noninvasive method for diagnosis of membranous obstruction
      of IVC or hepatic vein.

PMID- 8536751
TI  - Doppler color flow imaging for assessment and localization of pancreatic
      insulinoma.

PMID- 8536752
TI  - Ultrasound of intrascrotal calculi.

PMID- 8536753
TI  - The craniopharyngeal canal indicating the presence of pharyngeal adenopituitary
      tissue.

PMID- 8536754
TI  - MR of terminal myelocystoceles.
AB  - PURPOSE: To delineate the clinical and MR findings in children with an unusual
      type of spinal dysraphism, the terminal myelocystocele. Infants with a terminal
      myelocystocele carry a favorable neurologic prognosis if the entity is diagnosed
      early. Understanding the MR characteristics of this entity will allow for earlier
      and more accurate diagnosis. METHOD: Analysis of the medical charts and MR
      studies in 15 children with surgically and histologically proven myelocystocele.
      RESULTS: In all 15 children, MR demonstrated the primary findings of a terminal
      cyst of the central canal of the spinal cord which is tethered and herniated with
      arachnoid and cerebrospinal fluid through an area of spinal dysraphia onto the
      back as a mass. Of these children, 10 had additional findings (one or more) on MR
      of Chiari I (five cases), Chiari II (one case), cervicothoracic hydromyelia (two
      cases), lumbar hydromyelia (two cases), hydrocephalus (2 cases) segmentation
      anomalies of vertebrae (3 cases) and partial agenesis of sacrum (six cases). Of
      the clinical findings, all 15 children had a back mass, 10 also had cloacal
      exstrophy. One had imperforate anus, 10 were girls, five had ambiguous genitalia
      and all were neurologically intact. CONCLUSION: Children with a terminal
      myelocystocele present with a back mass and there is a high association with
      cloacal exstrophy. MR is the best noninvasive modality to diagnose all of the
      components of a terminal myelocystocele and the associated central nervous system
      findings.

PMID- 8536755
TI  - Delayed spontaneous migration of Gianturco-Rosch metallic stent from the biliary
      tree.

PMID- 8536756
TI  - Low-field magnetic resonance imaging in the evaluation of mechanical and
      biological heart valve function.
AB  - Magnetic resonance imaging (MRI) has been frequently considered unsafe for
      patients with ferromagnetic implants: risks to be considered include induction of
      electric current, heating and dislocation of the prosthesis. Previous in vitro
      and in vivo studies have indicated the possibility of performing MRI examinations
      on patients with prosthetic heart valves. The aim of our study was to verify the
      presence of artifacts at the level of the prosthetic heart valve in vivo using a
      low-field MR unit (0.2 T) and to define the possibility of a functional analysis
      of the valve in patients with biomedical or mechanical prostheses. We evaluated
      14 patients surgically treated for implantation of nine biological and seven
      mechanical aortic and mitral valves. A low-field MR unit (0.2 T) was employed
      using cine-MR technique on long- and short-axis view. The images were acquired on
      planes parallel and perpendicular to the valvular plane. Semiquantitative
      analysis with double-blind evaluation for definition of the extent of the
      artifact was performed. Three classes of artifacts were distinguished from
      minimal to significant. The examinations showed the presence of minimal artifacts
      in all biological heart valves and moderate artifacts in mechanical valves giving
      good qualitative data on blood flow near the valve. Analysis of the flow behind
      the valve showed signs of normal function in 13 prostheses and pathological
      findings in the remaining three. In these latter cases, MRI was able to define
      the presence of a pathologic aortic pressure gradient, mitral insufficiency and
      malpositioning of the mitral valve causing subvalvular turbulence. Nevertheless,
      we believe that the application of velocity-encoding cine-MR is more promising
      than semiquantitative analysis of artifacts.

PMID- 8536757
TI  - High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the
      EORTC-GCCG experience.
AB  - BACKGROUND: A dose-response relationship for doxorubicin in ovarian cancer (OC)
      cell lines has been demonstrated in vitro. However, this has never been carefully
      addressed in the clinic. These data and the more favourable toxicity profile of
      the anthracycline analogue epirubicin were reasons to study high-dose epirubicin
      (HDE) in OC patients who relapsed on/after platinum-based chemotherapy. This was
      done both in a phase I/II feasibility study (n = 27; HDE dose 120-200 mg/m2 q3
      weeks) and a still ongoing straightforward phase II study (n = 91; HDE dose 150
      180 mg/m2 q 3 weeks). RESULTS: Responses were observed at all dose levels.
      Overall 24 of the 118 patients responded (20%), which is much higher than
      reported with lower doses (7% with doses of 60-110 mg/m2). The most important
      side effects were myelosuppression, alopecia, nausea and vomiting and mucositis.
      CONCLUSION: HDE is tolerable and has activity in second-line after platinum-based
      chemotherapy in OC patients.

PMID- 8536758
TI  - Treatment of refractory ovarian carcinoma with paclitaxel and cisplatin after
      treatment failure with single-agent paclitaxel.
AB  - The clinical response to paclitaxel and cisplatin was evaluated in fifteen
      patients with refractory epithelial ovarian cancer who failed to respond to
      treatment with single agent paclitaxel. Patients received combination
      chemotherapy every 3 weeks with both 135 mg/m2 (9) or 175 mg/m2 (6) of paclitaxel
      and 50 mg/m2 (2), 75 mg/m2 (4) or 100 mg/m2 (9) of cisplatin. There was 1
      complete clinical response, with 2 partial clinical responses for an overall
      response rate of 20%. The progression free interval was 6+ months for the
      complete responder and 9.5+ months for the partial responders. Overall five (33%)
      patients experienced an improvement in clinical response over that seen with
      paclitaxel alone, and 5 patients have died. Improvement in clinical response with
      combination chemotherapy compared to paclitaxel alone was positively associated
      with the cisplatin dose; while disease progression and death were inversely
      associated with the paclitaxel dose. Addition of cisplatin to paclitaxel may be
      useful in the treatment of patients who fail to respond to paclitaxel alone.

PMID- 8536759
TI  - Influence of metronidazole and tamoxifen in a case of otherwise untreated
      ulcerous breast carcinoma.
AB  - A 78-year-old patient with an ulcerous, purulent, exophytic fist-sized breast
      carcinoma (FIGO IVd) and a pulmonary metastasis who refused radiation,
      chemotherapy and operation, was treated with oral tamoxifen and metronidazole
      daily and with local antiseptics. After two months she was pain-free without
      analgesics. After eight months the exophytic part of the tumor had completely
      gone. One year after the beginning of treatment, during which she had led a
      normal life, metronidazole was withdrawn due to neuropathy, and the wound
      worsened within a few days. One month later opioids were required to treat tumor
      induced pain. Two months later the patient died. The surprisingly long survival
      with good quality-of-life may indicate important effects of metronidazole
      combined with tamoxifen in the treatment of ulcerous breast cancer.

PMID- 8536760
TI  - Expression of the proto-oncogene bcl-2 in uterine cervical squamous cell
      carcinoma: its relationship to clinical outcome.
AB  - We studied bcl-2 expression in patients with uterine cervical squamous cell
      carcinoma and correlated this phenomenon with survival. Immunohistochemical
      analysis with a monoclonal antibody specific for bcl-2 was used to detect the
      protein in tumor samples from 259 patients undergoing surgery for squamous cell
      carcinoma of the uterine cervix. Of the total, 67% (174) of the tumors were bcl-2
      negative, and 33% (85) were positive. No significant difference in survival at
      five years was noted between patients with negative (78%) and positive (82%)
      tumors. However, when bcl-2 positive tumors were divided into partially stained
      (62 of 85, 73%), and diffusely stained (23 of 85, 27%) groups, the patients with
      partial staining had a better prognosis than those with diffused or negative (p <
      0.01), staining (p < 0.05) (5 year survivals, respectively; 92%, 61%, and 78%).
      Though detection of bcl-2 positivity may itself not have clinical value for
      uterine cervical squamous cell carcinoma, the staining characters may add to
      predicting prognosis.

PMID- 8536761
TI  - The role of low dose rate brachytherapy in the treatment of cervix carcinoma.
      Experience of the Gustave-Roussy Institute on 1245 patients.
AB  - From 1974 to 1992, 1245 patients with cervix carcinoma were treated at the
      Institut Gustave-Roussy using several treatment protocols all of which included
      LDR brachytherapy. We present and discuss the results of our experience.

PMID- 8536762
TI  - Proliferating cell nuclear antigen in benign breast diseases.
AB  - The expression of PCNA was examined by immunohistochemistry on 95 formalin-fixed
      breast surgical specimens. Seventy-four were benign breast disease, 3 atypical
      hyperplasia; 5 in situ carcinoma; 13 invasive carcinoma. Forty-two percent of
      benign breast disease, 75% of atypical hyperplasia/in situ carcinoma and 92% of
      invasive breast carcinoma expressed PCNA nuclear staining. Forty percent of
      cysts, 15.78% of sclerosing adenosis, 22.22% of adenosis, and 17.39% of
      epitheliosis expressed low cyclin protein levels (PCNA score I, < 18%); 20% of
      cysts, 31.57% of sclerosing adenosis, 5.55% of adenosis and 43.47% of
      epitheliosis expressed moderate levels (PCNA score II, 18 to 50%); whereas 50% of
      atypical hyperplasia/in situ carcinoma and 54% of invasive breast carcinoma
      contained high levels (PCNA score III, > 50%). This study on PCNA/cyclin
      localization suggests that PCNA is an early indicator of ongoing cellular
      proliferation.

PMID- 8536763
TI  - Multiple primary neoplasms. Considerations on 42 cases.
AB  - During the years 1977-1993, 2,108 cases of gynecologic primary neoplasms were
      observed in the Department of Gynecology and Obstetrics of La Sapienza University
      in Rome. Forty-two cases were multiple primary cancers. Of these, 27 had multiple
      primary neoplasms involving only gynecologic sites, 15 had a neoplasm involving
      also another site; 3 patients had triple primary neoplasms. The most frequent
      neoplasm associations observed in our case series were: breast-ovary; endometrium
      ovary; breast-cervix; endometrium-bowel (sigma-colon).

PMID- 8536764
TI  - Epithelial ovarian tumors in young women under 35 years.
AB  - The aim of this study was to investigate the clinical-pathological pattern of
      primary malignant epithelial ovarian tumors in women under 35 years old. We have
      retrospectively analyzed data from 545 patients with these tumors, identifying 49
      patients under age 35. We found a higher frequency of borderline tumors and early
      stage tumors in young women than in those over 35. The influence of age as a
      factor in survival was evaluated by comparing the outcome in young patients and
      in women over 35. The 5-year survival rate, according to stage and aggressiveness
      factors, was significantly better in young patients. These findings support the
      concept of a preclinical phase of epithelial carcinoma and show that young women
      may be selected for conservative surgery, allowing a good quality of life.

PMID- 8536765
TI  - Human papillomavirus detection in cervical smears and cervical tissue excised by
      the Loop Electrosurgical Excision Procedure (LEEP). Diagnostic value of cytology,
      colposcopy and histology.
AB  - A study was performed on 176 patients with benign cervical lesions. Human
      papillomavirus (HPV) structural antigens which were stained with the
      immunoperoxidase staining were sought for in cervical smears and in cervical
      tissues excised by the loop electrosurgical excision procedure (LEEP). HPV
      infection was found in 16.4% of the patients. Furthermore, cytologic screening on
      Papanicolaou (PAP) smears, colposcopy, and histologic examinations of whole
      transformation zones excised by the LEEP were performed. The diagnosis of HPV was
      based on the positive immunoperoxidase staining of either the exfoliated cells or
      the cervical tissue. HPV was detected on 5.6% of the PAP smears. The reliability
      of cytologic colposcopic, and histologic diagnosis of HPV was investigated.

PMID- 8536766
TI  - Tamoxifen, megestrol acetate, and beta interferon in endometrial cancer.
AB  - 22 patients with endometrial cancer were studied. Twelve (54.5%) between 45 and
      66 years were treated for six days before surgery with 160 mg per os of Megestrol
      acetate administered twice daily plus Beta interferon 3,000,000 IU- on alternate
      days for a week, plus Tamoxifen--two cp of 10 mg daily for six days. Before and
      after surgery and associated medical therapies the steroid receptor values (ER
      and PgR) were checked. After treatment an average increase was observed of the ER
      (19 fmol/mg) and PgR (17 fmol/mg). Of the twelve patients one died of a stroke
      during the study (8.33%); five (41.67%) showed complete remission (CR); four
      (33.34%) a partial remission (PR) and two (16.67%) were not responders (NR).

PMID- 8536767
TI  - Expression of p53 in benign breast diseases.

PMID- 8536768
TI  - Ovarian fibroma. A report of three cases.
AB  - The authors report three cases of ovarian fibroma in women in advanced menopause
      (mean age: 70 years). The neoplasm was bilateral in one patient. Early symptoms
      were pelvic pain, and, in one patient, menorrhagia without histologic alterations
      of the atrophic endometrium. The histology was typical of ovarian fibromas,
      except for one case which was characterized by a dense pseudofibrosarcomatous
      pattern and by the presence of numerous sex cord elements.

PMID- 8536769
TI  - Conclusions of the International Congress: "Panama on the prevention of cancer
      and sexually transmitted diseases".

PMID- 8536770
TI  - Advances and trends in hormonal therapy for advanced prostate cancer.
AB  - Hormonal therapy represents first-line treatment for patients with advanced
      prostate cancer. Generally, surgical castration is viewed as the 'gold standard'
      but carries with it a psychological effect. Medical alternatives include LHRH
      analogues, antiandrogens, and oestrogens, though the last of these is associated
      with cardiovascular problems. For complete androgen ablation, it is generally
      believed that androgens of both testicular and adrenal origin need to be blocked.
      Combined androgen blockade (CAB) by the addition of antiandrogen to castration
      (medical or surgical) may, therefore, be an appropriate treatment for advanced
      prostate cancer. Recent trials have shown that CAB may have treatment advantages
      compared with castration alone, and these benefits are greatest in patients with
      minimal metastatic disease. For these patients CAB may now be considered as
      standard therapy. In the treatment of non-metastatic disease, recent trends based
      on the experience gained in advanced prostate cancer include the possible use of
      hormonal therapy in neoadjuvant and adjuvant settings along with prostatectomy or
      radiotherapy. There is also growing interest in the use of intermittent rather
      than continuous hormonal therapy. New treatments offer an increasing range of
      management options to help improve the quality of life of prostate cancer
      patients.

PMID- 8536771
TI  - Attitudes of European urologists to early prostatic carcinoma. I. Diagnostic work
      up on suspected prostatic cancer cases.
AB  - The diagnostic work-ups of 656 European urologists on theoretical cases of
      suspected early prostatic carcinoma were surveyed. The diagnostic work-ups varied
      considerably among the urologists. There was strong agreement that digital rectal
      examination (DRE) and prostate-specific antigen (PSA) should be used routinely in
      these cases, but there was a lack of agreement concerning the use of transrectal
      ultrasound examination (TRUS), prostate biopsies and bone scan. However, the use
      of TRUS, bone scan and biopsies was correlated positively to the PSA level and
      negatively to age (p < 0.0001), but was not correlated to whether the patient was
      asymptomatic or suffered from prostatism. Ninety-two percent of the urologists
      would perform biopsies if a palpable lesion were present. If the PSA was
      elevated, 22% would use biopsies if it was 7 ng/l, 62% if it was 15 ng/l and 83%
      if it was 35 ng/l. These results indicate that a majority of European urologists
      would attempt to diagnose prostatic cancer with biopsies only when results of DRE
      and PSA predict a high risk that the cancer is no longer organ-confined.

PMID- 8536772
TI  - Attitudes of European urologists to early prostatic carcinoma, II. Attitude to
      therapy and to screening examinations.
AB  - The attitudes of 656 European urologists toward therapy of localized prostatic
      cancer (PC) and screening examinations of the male population for PC were
      surveyed. Eighty percent of the urologists would offer curative therapy to a 60
      year-old patient with localized PC, while 20% would offer watchful waiting or
      hormonal therapy. The choice of curative therapy was not correlated to the grade
      of the cancer. Radical prostatectomies were offered 2.5 times as often as
      external beam radiotherapy. The number of radical prostatectomies performed was
      considered to be increasing by 56% of the urologists surveyed, decreasing by 10%
      and stable by 34%. Fifty-five percent thought that screening for prostate cancer
      should be undertaken in their country, but only 35% believed this would decrease
      mortality from prostate cancer. A majority would include digital rectal
      examination, prostate-specific antigen and symptom evaluation in a screening
      program. Agreement among urologists from different European countries regarding
      the handling of early prostatic cancer is poor. Large regional differences were
      observed with a more active attitude to therapy and screening in southern and
      central Europe. Attitudes to screening and to therapy, however, were only weakly
      correlated. In conclusion, it seems paradoxal that many urologists who would
      offer curative therapies to patients with localized PC would not take steps to
      diagnose this disease via screening of the male population.

PMID- 8536773
TI  - Bladder neck preservation following radical prostatectomy: continence and
      margins.
AB  - Between December 1991 and January 1994, 134 patients underwent radical retropubic
      prostatectomy with bladder neck preservation. Forty-nine patients had a positive
      margin. Number and location of positive margins were analyzed. A tumor was
      identified at the bladder neck in 10 cases (7.5%). In all 10 patients with
      bladder neck involvement, a tumor was also identified at multiple other sites.
      These data suggest that preservation of the bladder neck during radical
      prostatectomy does not appear to compromise the efficacy of the procedure. Using
      a self-administered patient questionnaire, we evaluated the effect of bladder
      neck preservation upon continence in 36 patients. At the initial 3-month follow
      up, 24 (67%) patients did not wear any pads. Another 7 (19%) wore pads
      occasionally, while 5 (14%) patients wore pads daily. To date only 1 of the 134
      patients has developed an anastomotic stricture. Bladder neck preservation may
      aid in an earlier return of continence following radical prostatectomy and
      reduces anastomotic strictures. It does not appear to compromise the removal of
      the cancer.

PMID- 8536774
TI  - Maximum androgen deprivation prior to radical retropubic prostatectomy in
      patients with stage T3 adenocarcinoma of the prostate.
AB  - Eighty-two patients with stage T3 carcinoma of the prostate were treated for 3
      months prior to radical retropubic prostatectomy with a luteinizing-hormone
      releasing hormone analogue and an antiandrogen. Based on digital rectal
      examination (DRE), reduction of prostate and tumor size was noted in all cases.
      Ultrasound demonstrated a decrease in prostatic volume between 0 and 62.5%
      (median 32%). Prostate-specific antigen levels (PSA, Hybritech) decreased
      substantially (mean PSA of 29.5 ng/ml before to a mean PSA of 1.3 ng/ml after
      hormonal treatment). Pathologically, only 15 patients (18.3%) had organ-confined
      disease (stage pT2), 44 (53.7%) had stage pT3 tumors and 22 (26.8%) had positive
      lymph nodes. In 1 surgical specimen (1.2%), no residual tumor was identified. In
      5 patients with nodal metastasis and 13 patients with seminal vesicle invasion,
      PSA levels after pretreatment were below 0.5 ng/ml. Compared to the preoperative
      needle biopsy, a decrease in the histological grade was found in only 7 tumors,
      while an increase was noted in 26. DRE, ultrasound and PSA suggest a downstaging
      of stage T3 prostate cancer after 3 months of maximum androgen deprivation. This
      cannot be confirmed pathologically. Prospective studies with this treatment
      regimen should concentrate on a possible benefit concerning local and distant
      cancer control and survival.

PMID- 8536775
TI  - A randomised comparison of monotherapy with Casodex 50 mg daily and castration in
      the treatment of metastatic prostate carcinoma. Casodex Study Group.
AB  - Casodex (Bicalutamide, ICI 176,334) is a potent, non-steroidal, selective anti
      androgen with a long half-life allowing once-daily oral administration. In this
      randomised, open, multicentre study, Casodex 50 mg monotherapy was compared with
      castration (medical, using goserelin acetate, [Zoladex], or surgical) in 245
      patients with advanced prostate cancer. Primary end-points were time to treatment
      failure, time to objective progression and survival. Subjective responses,
      quality of life and tolerability were also evaluated. There was no significant
      difference between the groups in terms of objective progression or subjective
      responses. Treatment failed in 59 of 119 patients (50%) randomised to Casodex and
      in 61 of 126 patients (48%) randomised to castration (no statistically
      significant difference). An updated analysis showed that survival was similar in
      the two groups. Casodex was well tolerated with a low incidence of diarrhoea and
      sexual dysfunction. On the basis of this study, Casodex monotherapy is an
      effective alternative to castration in the treatment of metastatic prostate
      cancer.

PMID- 8536776
TI  - Terazosin and doxazosin in normotensive men with symptomatic prostatism: a pilot
      study to determine the effect of dosing regimen on efficacy and safety.
AB  - In this pilot study, the effect of dosing schedule on the efficacy and safety of
      the long-acting alpha 1-adrenergic blockers, terazosin (TER) and doxazosin (DOX),
      was evaluated in 43 consecutive normotensive men (mean age 59.6 years) with
      symptoms of prostatism. Patients were randomized to one of four treatment groups:
      (1) TER 5 mg once in the morning (AM; n = 10), (2) TER 5 mg once in the evening
      (PM; n = 11), (3) DOX 4 mg once AM (n = 11), and (4) DOX 4 mg once PM (n = 11).
      Patients were titrated to their final dose over 3 weeks. Parameters evaluated
      included Boyarsky symptom score (Sx), peak uroflow (Qmax), blood pressure and
      occurrence of adverse events. Once stabilized, patients were seen at 3-month
      intervals; follow-up ranged from 4 to 17 months (mean 9.7). Clinical improvement
      as determined by Sx and Qmax was similar for all four treatment groups. Mean
      decreases in Sx at 3 months were 4.6, 5.4, 4.9, and 5.0 for TER-AM, TER-PM, DOX
      AM, and DOX-PM, respectively. Mean peak uroflow increased 3.0, 3.1, 2.8, and 3.1
      ml/s for TER-AM, TER-PM, DOX-AM, and DOX-PM, respectively (p < 0.05 vs.
      baseline). Eight patients (18%) were withdrawn from the study because of adverse
      events (fatigue 1, asthenia 1, headache 3, dizziness 4): 5 during the titration
      phase (TER-AM: 2, DOX-AM: 2, TER-PM: 1) and 3 during the treatment phase (TER-AM:
      2, DOX-AM: 1). In these 8 patients, the mean decreases in sitting and standing
      blood pressure were approximately 7/5 and 10/8 mm Hg, respectively. These data
      suggest that efficacy of TER and DOX was similar at the dosages employed and not
      affected by the dosing schedule. Adverse events in this small population were
      significantly decreased (p < 0.05) by dosing in the PM. These preliminary results
      suggest that a larger prospective study is warranted to determine (1) the
      comparative efficacy of TER and DOX in the treatment of symptomatic benign
      prostatic hyperplasia and (2) optimal timing of the medication.

PMID- 8536777
TI  - Depot medroxyprogesterone in the management of benign prostatic hyperplasia.
AB  - The effects of depot medroxyprogesterone (DMPA), a 5 alpha-reductase, luteinizing
      hormone release and human androgen receptor adhesion inhibitor, were assessed in
      80 patients with benign prostatic hyperplasia (BPH) in a double-blind, placebo
      controlled study. Patients were randomized to DMPA 150 mg single-dose
      intramuscular injection or placebo in a similar fashion. The following changes
      were seen with DMPA after 3 months (duration of DMPA effect): (1) serum
      testosterone reached castration levels within 3 days as compared to no changes in
      the placebo group; (2) the prostate volume was reduced by 25% compared to a 3%
      decrease with placebo (p < 0.001); (3) maximum urinary-flow rates increased by
      3.7 ml/s compared to placebo (p < 0.001); (4) total urinary symptom scores
      decreased by 4.9 points compared to a nonsignificant decrease with placebo (p <
      0.005). There was a 2.5-point decrease in irritative symptoms (urinary frequency,
      nocturia and urgency) as compared to a nonsignificant decrease with placebo (p <
      0.005). After 3 months, the urinary symptoms and urodynamic changes were reversed
      but significantly greater than the baseline values (p < 0.001). The prostates
      showed regrowth to the initial sizes within 18-36 weeks. DMPA was better
      tolerated, except for a higher incidence of impotence, decreased libido and
      ejaculatory disorders, than in the placebo group. The quality of life is improved
      with DMPA since it did not produce hot flashes. It was concluded that single-dose
      DMPA 150 mg is a safe and effective treatment for prostatic obstruction where
      potency is a secondary consideration.

PMID- 8536778
TI  - Treatment of Peyronie's disease with local interferon-alpha 2b.
AB  - Peyronie's disease is an illdefined condition that often leads to severe penile
      deformity. Various conservative treatments have failed to have any impact, and
      surgery remains the mainstay of therapy in advanced cases. Recent reports of
      successful treatment of related diseases, notably keloid formation, with
      interferons (INF) have prompted us to use this biologic response modifier to
      alter the behavior of the myofibroblast, the cell most likely responsible for the
      development of Peyronie's disease. From December 1992 to July 1994, 25 patients
      suffering from Peyronie's disease were treated with five local injections of 1
      million units of INF-alpha 2b each into a single designated and
      ultrasonographically measured plaque. The interval between the injections was 1
      week. The patients were assessed clinically and ultrasonographically 1 and 6
      months after the last injection. The condition improved clinically in only 1
      case, but progressed in none. The measured plaque size decreased in 7 no or
      mildly calcified cases, remained stable in 12 cases, and increased in 6 patients,
      (solely calcified plaques). Side effects (myalgia, fever) occurred in 4 patients;
      of these 2 patients withdrew from treatment. INF-alpha 2b given according to our
      regimen is at best usefull for the treatment of Peyronie's disease in the early,
      noncalcified stage during which it displays verifiable impact on the plaque
      treated and also helps alleviate the plaque-associated pain; but further dose
      finding studies will have to be performed to identify clinically relevant
      treatment regimens.

PMID- 8536779
TI  - Aetiology of priapism in 207 patients.
AB  - Two hundred and seven patients were treated for priapism in Finnish hospitals in
      1973-1990. In order to analyse the aetiology of priapism, the original data on
      these and on 163 age- and time-matched controls, who underwent appendicectomy,
      were collected from the hospitals. The information was completed by collecting
      extra data from other hospitals and health centres or by personal contacts. In 43
      of the 207 cases (21%), the cause of priapism was an intracavernous injection of
      a vaso-active drug. These patients were excluded from the logistic regression
      analysis used to evaluate the most essential factors associated with priapism.
      They were found to abuse alcohol (p < 0.001), use psychopharmaceuticals (p <
      0.001), antihypertensive drugs (p = 0.003), anticoagulants (p = 0.005), as well
      as to have lumbar disc pain (p = 0.002) and chronic prostatitis (p = 0.01).
      Smoking was also significantly more common in the patients affected by priapism
      (56%) than in the controls (33%), being significantly associated with heavy
      alcohol drinking and use of psychopharmaceuticals. A disease or trauma was a
      possible causative factor in one third of the patients. The present study
      confirms the suggestion of a multifactorial aetiology for the initiation of
      priapism.

PMID- 8536780
TI  - Opiate antagonists in erectile dysfunction: a possible new treatment option?
      Results of a pilot study with naltrexone.
AB  - Opioids have an inhibitory effect on sexual functions in both animals and humans.
      Twenty patients with idiopathic, nonvascular, nonneurogenic erectile dysfunction
      were treated with the opiate receptor antagonist naltrexone in a randomized,
      placebo-controlled, double-blind study for 8 weeks. Libido and frequency of
      sexual intercourse were not significantly altered, but early-morning erections
      increased significantly under naltrexone therapy. This response was not related
      to levels of androgens or gonadotropins, neither was it dose dependent. There was
      no change in any of the measured parameters under placebo. Further clinical
      studies with the substance should be conducted to evaluate its possible role in
      the oral treatment of male impotence.

PMID- 8536781
TI  - Expression of a cell surface antigen recognized by the monoclonal antibody AUA1
      in bladder carcinoma: an immunohistochemical study.
AB  - The expression of a cell surface antigen recognized by the epithelium-specific,
      tumor-associated monoclonal antibody (Moab) AUA1 has been studied in 22 cases of
      normal urothelium, 7 cases of dysplastic urothelium and 86 cases of transitional
      cell carcinoma. Tissue specimens were stained with the conventional hematoxylin
      eosin technique as well as with the indirect immunoperoxidase technique using
      Moab AUA1. Results showed that: (a) Moab AUA1 reacts mainly with cells of high or
      intermediate grade transitional cell carcinoma and with a restricted number of
      normal urothelial cells, and (b) antigenic heterogeneity exists between tumors of
      the same grade and within the same tumor.

PMID- 8536782
TI  - Oxytocin-induced contractions of the rabbit corpus cavernosum.
AB  - The contractile effect of oxytocin on isolated rabbit corpus cavernosum strips
      was investigated. Concentration-response curves to oxytocin and phenylephrine
      were obtained. Oxytocin repetitively induced concentration-dependent contractions
      in the corpus cavernosum strips. The maximal contractile response to oxytocin was
      in amplitude 39.4 +/- 9.1% of that to phenylephrine. The slopes of the
      concentration-response curves, the amplitude of the maximal contractile effects,
      and the pD2 values of oxytocin obtained in endothelium-denuded strips were not
      significantly different from those of intact preparations. The results of this
      study demonstrated that oxytocin contracts the rabbit corpus cavernosum, but the
      endothelium does not contribute to this effect. Since oxytocin is less
      efficacious than phenylephrine, it seems unlikely that this hormone can serve as
      an alternative in the treatment of prolonged penile erections.

PMID- 8536783
TI  - Role of cyclic adenosine monophosphate in prostaglandin E1-induced penile
      erection in rabbits.
AB  - To investigate the role of cyclic adenosine monophosphate (cAMP) in penile
      erection in relation to the effect of prostaglandin E1 (PGE1) male adult New
      Zealand white rabbits were utilized as a model to study intracavernous pressure
      (ICP) in vivo. After intracavernous injection of PGE1 (0.2-1.6 micrograms/kg) and
      8-bromocyclic adenosine monophosphate (8-Br-cAMP, 0.5-1.5 mg/kg), both drugs
      raised the ICP in a dose-dependent manner. The increased ICPs induced by PGE1 and
      8-Br-cAMP were 33.4 +/- 8.12 and 24.1 +/- 4.9 mm Hg, respectively (p < 0.05,
      paired Student's t test). Administrations of cyclic adenosine monophosphothioate,
      Rp-isomer (cAMP antagonist, 0.02-0.08 mumol/kg) prior to PGE1 injections
      inhibited the effect of PGE1 in vivo in a dose-dependent manner. The systemic
      blood pressures and heart rates in rabbits were unchanged during all the
      intracavernous injections. The corpus cavernosal tissues isolated from rabbits
      were studied for the cAMP contents after incubation of different doses of PGE1 in
      vitro. The cAMP contents were also elevated in a manner parallel with the
      increases in PGE1 concentrations (3-9 microM). We conclude: (1) the feasibility
      of intracavernous injection of vasoactive drugs is similar to that in man, thus
      the rabbit can be used as a suitable alternative for the studies of penile
      erection, and (2) cAMP is mediated in PGE1-induced relaxation of the rabbit
      corpus cavernosum, and the cAMP system only participates partially in penile
      erection.

PMID- 8536784
TI  - Digestive mucosal graft in urethroplasty.

PMID- 8536785
TI  - Constitutive and modulated cytokine expression in two permanent human bone marrow
      stromal cell lines.
AB  - We present a detailed analysis of cytokine expression patterns of the two
      permanent human bone marrow stromal cell lines, L87/4 and L88/5. These cell
      lines, previously established in our laboratory, are highly radiotolerant without
      cell detachment and support long-term cultures of CD(34+)-enriched human cord
      blood cells. RT-PCR analysis of 22 different cytokines or cytokine receptor mRNAs
      showed an almost identical expression pattern in the two stromal cell lines
      compared to primary human Dexter-type stroma. Since stromal feeder lines employed
      in long-term cultures usually are irradiated and grown in media containing
      corticosteroids, we analyzed the impact of irradiation and dexamethasone on
      cytokine production in the two cell lines by RT-PCR, Northern blot analysis,
      bioassays, and RIAs. By RT-PCR analysis, constitutive mRNA expression of c-kit, G
      CSF, GM-CSF, IL-1 beta, IL-6, IL-7, IL-8, IL-11, Kit ligand (KL), LIF, M-CSF, MIP
      1 alpha, TGF-beta, and TNF-alpha was demonstrated in both cell lines, with L87/4
      a more potent cytokine producer than L88/5. Northern blot data showed an increase
      in mRNA levels for GM-CSF, IL-1 beta, and LIF by irradiation and IL-1 alpha
      treatment in both cell lines. IL-1 alpha-induced GM-CSF, IL-1 beta, IL-6, IL-11,
      and LIF mRNA levels were reduced by the addition of dexamethasone, whereas
      dexamethasone had no influence on the amounts of IL-1 alpha-induced G-CSF mRNA.
      L87/4 and, to a lower extent, L88/5 cells showed dexamethasone-dependent
      increases in KL mRNA, while KL mRNA levels were not stimulated by IL-1 alpha.

PMID- 8536786
TI  - Serum granulocyte colony-stimulating factor (G-CSF) and interleukin-1 (IL-1)
      concentrations after chemotherapy-induced neutropenia in normal and tumor-bearing
      dogs.
AB  - Hematopoiesis is regulated by complex interactions of hematopoietic growth
      factors known as colony-stimulating factors and interleukins. We used sensitive
      bioassays to quantitate serum granulocyte colony-stimulating factor (G-CSF) and
      interleukin-1 (IL-1) concentrations in normal and tumor-bearing dogs following
      administration of myelosuppressive chemotherapy (vincristine, doxorubicin,
      cyclophosphamide). Serum G-CSF and IL-1 increased during the neutrophil nadir in
      13 of the 16 dogs. Serum G-CSF concentrations were significantly increased in
      normal and in tumor-bearing dogs on neutropenic compared to non-neutropenic days.
      Serum IL-1 concentrations increased significantly on neutropenic days in normal
      dogs but not in tumor-bearing dogs. A marked neutrophilia was observed in normal
      dogs, but not in tumor-bearing dogs, following the increases in serum G-CSF and
      IL-1 concentrations (days 7, 8, and 9, p < 0.05). Normal dogs produced
      significantly more G-CSF on neutropenic days compared to dogs with lymphoma. On
      non-neutropenic days, serum IL-1 concentrations were significantly increased in
      dogs with lymphoma and in dogs with nonlymphoid malignancies compared to normal
      dogs. These results suggest an important role for G-CSF and IL-1 in hematopoietic
      recovery after chemotherapy-induced myelosuppression and document an altered
      hematopoietic regulation in animals with malignancy compared to normal subjects.

PMID- 8536787
TI  - Pluripotent stem cells constitutively expressing a normal erythropoietin receptor
      give rise to normal hematopoiesis in lethally irradiated recipient mice.
AB  - The cellular mechanism by which the stem cell differentiates toward an individual
      myeloid lineage is unknown. To determine whether lineage-specific cytokines are
      involved in stem cell determination, murine bone marrow cells were infected with
      a retroviral vector carrying a murine erythropoietin receptor (EpoR) cDNA.
      Infected marrow cells were transplanted into lethally irradiated syngeneic
      recipient mice, and the effect of Epo was studied on EpoR-expressing pluripotent
      stem cell determination. The graft contained, among myeloid cells, around 100 CFU
      S12, half of which were retrovirally infected. One month after grafting, the bone
      marrow of mice reconstituted with EpoR-infected cells contained 50 times more
      infected multipotent progenitors than mice reconstituted with control bone marrow
      cells. However, this number returned to normal 45 days after the graft. No
      variation was observed in peripheral blood, bone marrow, and spleen cellularities
      or in committed progenitors in the bone marrow and in the spleen when Neo or EpoR
      reconstituted mice were assayed. When Epo was delivered into reconstituted mice
      one month after grafting, Epo had no differential effect in EpoR or Neo
      reconstituted mice. This study emphasizes the in vivo Epo proliferative response
      of multipotent progenitors expressing a normal EpoR gene and shows that, in vivo
      as in vitro, the differentiation of these multipotent progenitors is not
      preferentially oriented toward erythropoiesis.

PMID- 8536788
TI  - Increased production of interleukin-6 by T lymphocytes from patients with
      multiple myeloma.
AB  - Alterations in T lymphocyte functions may affect other cellular components of the
      immune system. Several lymphokines produced by T cells are involved in the
      proliferation and differentiation of human B lymphocytes. Alterations in the
      secretion of these molecules may be implicated in the development of B cell
      lymphoproliferative diseases. We have investigated the production of interleukin
      2 (IL-2) and interleukin-6 (IL-6) by T lymphocytes from 14 patients with multiple
      myeloma (MM) and 16 healthy controls. The phenotypical and functional
      characteristics of these T lymphocytes were also studied. The proliferative
      response to vegetal lectin phytohemagglutinin (PHA) stimulation was decreased in
      T lymphocytes from MM patients (p < 0.01). This defective proliferative response
      cannot be ascribed to either defective IL-2 production or diminished receptor
      expression, since neither of these parameters showed a significant difference
      between MM patients and healthy controls (p < 0.05). However, the defective
      proliferative response of T lymphocytes from MM patients was reverted by the
      addition of saturating amounts of exogenous IL-2 (p > 0.05) but not by exogenous
      IL-6 (p < 0.05). The IL-6 production by PHA-stimulated T lymphocytes from the MM
      patients was significantly higher than in healthy controls (p < 0.01). We
      conclude that T lymphocytes from MM patients show a functional alteration with a
      defective proliferative response to PHA that is reverted by exogenous addition of
      IL-2. After lectin stimulation, the production of IL-2 by T lymphocytes from
      those patients was normal, while IL-6 secretion was increased.

PMID- 8536789
TI  - Production of hematopoietic regulatory cytokines by peripheral blood mononuclear
      cells in patients with aplastic anemia.
AB  - The aim of this study was to measure the level of cytokines produced by
      peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA)
      and determine their effect on normal bone marrow (BM) colony growth. Thirty-five
      patients with AA and 21 normal controls were enrolled in the study. Medium
      conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA)
      was found to be suppressive to the clonal growth of normal BM cells. Thus, we
      further determined the presence in the PBMNC conditioned medium (CM) of
      inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha],
      transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and
      tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte
      macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem
      cell factor [SCF]). The results show no significant difference between AA
      patients and normal controls in the spontaneous production of all cytokines by
      PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF
      alpha, and GM-CSF significantly increased in the cultures of AA patients (p =
      0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and
      SCF were undetectable in most of the tested samples. IL-3 was measured in the
      conditioned medium only after PHA stimulation, but without significant difference
      between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing
      effect of AA-PBMNC CM could be significantly blocked by pretreatment with
      specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN
      gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred
      in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in
      colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and
      anti-TNF-alpha, respectively. These results suggest that overproduction of
      inhibitory cytokines, rather than underproduction of stimulating cytokines, may
      play a role in the progression of at least some patients with AA.

PMID- 8536790
TI  - Induction of differentiation and enhancement of vincristine sensitivity of human
      erythroleukemia HEL cells by vesnarinone, a positive inotropic agent.
AB  - We examined the effect of vesnarinone, an oral cardiotonic, on the growth and
      differentiation of human myeloid leukemia cells. Vesnarinone alone markedly
      induced erythroid differentiation of HEL cells. All-trans-retinoic acid also
      induced erythroid differentiation of the cells, and the differentiation was
      greatly enhanced by combined treatment with vesnarinone and retinoic acid. HEL
      cells are highly resistant to some anticancer drugs, including vincristine, but
      treatment with vesnarinone greatly increased the sensitivity of HEL cells to
      vincristine. Enhancement of vincristine sensitivity by vesnarinone was not as
      significant for other leukemia cells. Expression of P-glycoprotein in HEL cells
      was effectively inhibited by vesnarinone, suggesting that the restoration of
      vincristine sensitivity is associated with decrease of P-glycoprotein expression
      in HEL cells. The plasma level of vesnarinone required to induce differentiation
      of leukemia cells is 30 micrograms/mL, which could be achieved with oral
      administration. These results suggest that vesnarinone should be useful in
      differentiation therapy for some types of myelogenous leukemia.

PMID- 8536791
TI  - Phorbol ester-mediated regulation of CD10/neutral endopeptidase transcripts in
      acute lymphoblastic leukemias.
AB  - The cell-surface zinc metalloproteinase CD10/neutral endopeptidase 24.11
      (CD10/NEP) hydrolyzes a variety of peptide substrates and regulates related
      peptide-mediated cellular responses. Because the enzyme functions as part of a
      peptide regulatory loop, the fact that CD10/NEP itself varies with cellular
      activation is of considerable interest. In hematopoietic and nonhematopoietic
      cell types, the levels of CD10/NEP protein and enzymatic activity correlate with
      transcript abundance. For these reasons, we investigated the regulation of
      CD10/NEP transcripts in the phorbol ester-treated acute lymphoblastic leukemia
      cell line, REH. When REH cells are treated with phorbol myristate acetate (PMA),
      CD10/NEP transcripts rapidly decrease in a labile protein-dependent manner. PMA
      has a modest effect on CD10/NEP transcription and significantly reduces CD10/NEP
      mRNA stability. Of note, the predicted secondary structure of the CD10/NEP 3'
      untranslated region includes several stem loop structures that may affect the
      stability of CD10/NEP transcripts.

PMID- 8536792
TI  - Tumor necrosis factor administration is associated with increased endogenous
      production of M-CSF and G-CSF but not GM-CSF in human cancer patients.
AB  - In humans, tumor necrosis factor (TNF) treatment has been associated with
      characteristic changes in circulating white blood cell populations (leukopenia
      followed by leukocytosis) and increased cell-surface expression of integrins. A
      similar pattern of effects on leukocytes occurs with granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and G-CSF treatment. To determine whether
      these effects were caused directly by TNF or as a result of secondary CSF
      release, G-GM-, and M-CSF levels were measured after TNF infusion (9.6 x 10(6)
      U/mg protein; < 5.0 endotoxin U/mg protein) in cancer patients during two phase I
      trials of TNF. One patient with aggressive fibromatosis was treated with TNF
      alone (200 micrograms/m2, days 1-5 every third week) and 10 patients (four colon
      cancer, four head and neck cancer; one melanoma; one sarcoma) received mitomycin
      C (15 mg/m2, day 1) followed by TNF (60-180 micrograms/m2, days 1-3) every sixth
      week. All treatments were given IV, mitomycin C over 5 minutes and TNF over 2
      hours. Serum samples were collected at times 0 (before mitomycin C and TNF) and
      1, 2, 4, 6, 12, and 24 hours after TNF initiation on day 1 and at similar times
      on subsequent treatment days. M-CSF samples were analyzed by radioimmunoassay
      (RIA) and G-CSF and GM-CSF by ELISA. The mean baseline M-CSF levels in normal
      control subjects (n = 12) was 158.4 +/- 36.2 (SD) U/mL, and in pretreatment
      cancer patients (n = 10) 235.7 +/- 60.9 U/mL (p = 0.004, Wilcoxon test). M-CSF
      levels increased 4 hours after TNF initiation (mean 354.7 +/- 96.3 U/mL; p =
      0.020), remained elevated at 6 hours (305.6 +/- 45.4 U/mL; p = 0.004, Wilcoxon
      signed-rank test), and subsequently declined. This pattern was seen in all
      patients treated with TNF, whether treatment was TNF alone or TNF with mitomycin
      C. In patients treated with mitomycin C and TNF, G-CSF levels increased at 4
      hours after TNF initiation (mean 3886 +/- 2009 pg/mL; p = 0.004), remained
      elevated at 6 hours (mean 2140 +/- 1131 pg/mL; p = 0.004), and subsequently
      declined. GM-CSF levels were not measurable before or after treatment with TNF.
      The changes in all three endogenous cytokines were not temporally related to the
      previously described leukopenia and integrin upregulation on circulating
      leukocytes and, therefore, appear to be unrelated to this event. However, release
      of endogenous G-CSF and M-CSF under the influence of TNF does temporally coincide
      with the previously described leukocytosis, suggesting a possible role for these
      endogenous cytokines in the release of bone marrow cellular stores.

PMID- 8536793
TI  - Erythropoietin-like activity in vivo of the fusion protein rhIL-6/IL-2 (CH925).
AB  - CH925 is a novel cytokine of a fusion protein interleukin-6 (IL-6)/IL-2
      exhibiting erythropoietin (Epo)-like effects in vivo and ex vivo, in addition to
      its enhanced effects compared to IL-2 and IL-6 reported by us previously, which
      indicates its potential clinical use. Our present study was undertaken to
      determine the Epo-like activity of CH925 in vivo. The reticulocyte response was
      observed in transfusion-induced polycythemic mice by using flow cytometry with
      pyronin Y staining. On day 2 after injection of CH925, the average number of
      reticulocytes was 2.11% in the group given 250 micrograms/kg/d and 1.01% for 100
      micrograms/kg/d. The mean fluorescence intensity (MFI) also significantly
      increased. Longitudinal studies of CH925 were performed on days 2, 4, and 10, and
      reticulocyte counts increased up to a peak on day 4. Activity of CH925 (100
      micrograms/kg/d) corresponds to 1 U of standard rhEpo in our study.

PMID- 8536794
TI  - Mycophenolic acid suppresses protein N-linked glycosylation in human monocytes
      and their adhesion to endothelial cells and to some substrates.
AB  - Mycophenolic acid (MPA) is the active part of the corresponding morpholinoethyl
      ester pro-drug Mycophenolate Mofetil. MPA, an inhibitor of IMP dehydrogenase,
      depletes GTP and thereby suppresses transfer of mannose and fucose to proteins.
      Treatment of human monocytes with a clinically attainable concentration of MPA
      (10 microM) decreases their attachment to endothelial cells and to laminin, but
      not to type I collagen or fibronectin. Our results not only elucidate a major
      role of mannose/fucose residues in homing of monocytes on activated endothelium
      but also explain in part the beneficial effects of MPA in rheumatoid arthritis
      and organ graft rejection.

PMID- 8536795
TI  - Sickling in vitro of reticulocytes from patients with sickle cell disease at
      venous oxygen tension.
AB  - Changes in the degree of sickling in vitro of reticulocytes and nonreticulocytes
      from patients with sickle cell disease were studied under complete deoxygenation
      (PO2 = 0 mm Hg) and partial deoxygenation (PO2 = 30 mm Hg, the average PO2 in the
      venous circulation) conditions at pH 7.4. Degree of sickling was quantitated by
      image analysis after identification of reticulocytes by acridine orange staining.
      Sickling in vitro of reticulocytes and nonreticulocytes under complete
      deoxygenation was similar and relatively unchanged during a 2-hour incubation. In
      contrast, under partially deoxygenated conditions, at least two populations of
      reticulocytes were apparent, one more susceptible to sickling than the other;
      nonreticulocytes were generally less susceptible to sickling. Many of the
      severely deformed reticulocytes showed formation of long spicules during
      incubation. These data suggest that a subset of reticulocytes are more
      susceptible to sickling than nonreticulocytes, and that the degree of
      reticulocyte sickling in vitro increases dramatically with time even at constant
      partial oxygen pressures observed in the venous circulation. Since dehydration in
      sickled reticulocytes seemed to be proceeding, mechanisms of inhibition were also
      examined. We found that quinine, an inhibitor of the Ca(++)-activated K+ efflux,
      inhibited part of the reticulocyte sickling while okadaic acid, a K(+)-Cl- co
      transport inhibitor, did not inhibit sickling under our experimental conditions.
      These phenomena observed at pH and oxygen tension similar to physiological venous
      conditions may be important in understanding the clinical course and
      pathophysiology of sickle cell disease.

PMID- 8536796
TI  - The synthetic tetrapeptide AcSDKP protects cells that reconstitute long-term bone
      marrow stromal cultures from the effects of mafosfamide (Asta Z 7654).
AB  - The tetrapeptide AcSDKP (Seraspenide) has been described as an inhibitor of CFU-S
      entry into DNA synthesis; as a result, its administration can protect mice
      against lethal doses of cytosine arabinoside. We have studied the ability of
      AcSDKP to protect and promote the growth of early CD34+ human bone marrow (BM)
      stem cells in Dexter long-term cultures following exposure to a toxic
      concentration of mafosfamide. The protection assay was based on the preincubation
      of CD34+ BM cells with or without AcSDKP at 10(-10)M or 10(-8)M followed by
      exposure to a toxic dose of mafosfamide (100 micrograms/mL). The production of
      granulomonocytic progenitor cells (CFU-GM) was subsequently studied in long-term
      bone marrow cultures (LTBMC) of the samples exposed to mafosfamide and
      preincubated or not (control) with AcSDKP. After a lag of 2 to 3 weeks, the
      number of CFU-GM peaked at the 4th to 5th week in both the supernatant and the
      adherent layers. A greater production of granulomonocytic progenitor cells was
      observed in LTBMC from the samples preincubated with AcSDKP compared with control
      cells. Depending on the BM samples, enhanced production of CFU-GM in the AcSDKP
      treated cell cultures was observed at either the 10(-10)M or 10(-8)M
      concentration. These results suggest that AcSDKP can protect in vitro human long
      term culture-initiating cells (LTC-IC) from mafosfamide, resulting in an
      increased production of CFU-GM from this early stem cell compartment.

PMID- 8536797
TI  - Methodologic considerations for the use of canine in vivo aged biotinylated
      erythrocytes to study RBC senescence.
AB  - Biotinylation of erythrocytes has been developed in rabbits as a tool to retrieve
      labeled cells following various periods in circulation. This retrieval capability
      allows biochemical studies to be conducted on red blood cells (RBC) that have
      aged for desired times in vivo. However, because erythrocyte life span is much
      shorter in rabbits than in humans, and because cell removal is measurably age
      independent in rabbits, we have sought to validate the same protocol in dogs,
      whose cell life span and age-dependent removal characteristics are similar to
      humans'. Canine RBC were biotinylated in vivo by infusion of N
      hydroxysuccinimidyl biotin dissolved in dimethylacetamide or dimethylsulfoxide.
      Cell life spans were evaluated using 14C-cyanate labeling followed by
      scintillation counting or avidin-FITC labeling followed by flow cytometry. Both
      methods gave identical results. The life span of the biotin-conjugated cells was
      found to be normal (approximately 110 days), and the stability of the biotin
      ligand was adequate for efficient retrieval of cells using avidin-coated magnetic
      beads (magnetic cell sorting [MACS]). From each isolation, approximately 20
      microL of packed biotinylated cells of approximately 90% purity (i.e., 10%
      contamination by unlabeled cells) could be harvested. On average, approximately
      60% of the biotinylated cells in any sample could be retrieved. Either multiple
      isolations or use of larger collection columns will facilitate collection of cell
      numbers sufficient for biochemical tests. After incorporating several
      modifications in the previous biotinylation protocol that were required for
      adaptation to the dog, the methodology can be used to study red cell senescence
      in an animal that has several pertinent similarities to humans.

PMID- 8536798
TI  - Consensus phylogeny of Dictyostelium.
AB  - The evolutionary relationship of Dictyostelium discoideum to the yeasts, fungi,
      plants, and animals is considered on the basis of physiological, morphological
      and molecular characteristics. Previous analyses of five proteins indicated that
      Dictyostelium diverged after the yeasts but before the metazoan radiation.
      However, analyses of the small ribosomal subunit RNA indicated divergence prior
      to the yeasts. We have extended the molecular phylogenetic analyses to six more
      proteins and find consistent evidence for a more recent common ancestor with
      metazoans than yeast. A consensus phylogeny generated from these new results by
      both distance matrix and parsimony analyses establishes Dictyostelum's place in
      evolution between the yeasts Saccharomyces cerevisiae and Schizzosaccharomyces
      pombe and the worm Caenorhabditis elegans.

PMID- 8536799
TI  - Analysis of gene function in Dictyostelium.
AB  - Over the past ten years, powerful molecular genetic techniques have been
      developed to analyze gene function in Dictyostelium. DNA-mediated transformation
      using a variety of selections and vectors has allowed the introduction of wild
      type or modified genes that are under various forms of transcriptional control.
      Homologous recombination is efficient and can be used to modify the genome in
      precise ways. In addition, it is now possible to clone genes based on their
      mutant phenotype alone, either by insertional mutagenesis, or by screening
      antisense expression cDNA libraries. Finally, a nearly complete physical map of
      the genome is available and so genes are easily mapped by physical techniques. We
      discuss many of these advances within the context of major research problems
      presently under study.

PMID- 8536800
TI  - PSF and CMF, autocrine factors that regulate gene expression during growth and
      early development of Dictyostelium.
AB  - Throughout growth and development, Dictyostelium cells secrete autocrine factors
      that accumulate in proportion to cell density. At sufficient concentration, these
      factors cause changes in gene expression. Vegetative Dictyostelium cells
      continuously secrete prestarvation factor (PSF). The bacteria upon which the
      cells feed inhibit their response to PSF, allowing the cells to monitor their own
      density in relation to that of their food supply. At high PSF/bacteria ratios,
      which occur during late exponential growth, PSF induces the expression of several
      genes whose products are needed for cell aggregation. When the food supply has
      been depleted, PSF production declines, and a second density-sensing pathway is
      activated. Starving cells secrete conditioned medium factor (CMF), a glycoprotein
      of Mr 80 kDa that is essential for the development of differentiated cell types.
      Antisense mutagenesis has shown that cells lacking CMF cannot aggregate, and
      preliminary data suggest that CMF regulates cAMP signal transduction.
      Calculations indicate that a mechanism of simultaneously secreting and
      recognizing a signal molecule, as used by Dictyostelium to monitor cell density,
      could also be used to determine the total number of cells in a tissue.

PMID- 8536801
TI  - The Dictyostelium cytoskeleton.
AB  - New avenues of cytoskeleton research in Dictyostelium discoideum have opened up
      with the cloning of the alpha- and beta-tubulin genes and the characterization of
      kinesins and cytoplasmic dynein. Much research, however, continues to focus on
      the actin cytoskeleton and its dynamics during chemotaxis, morphogenesis, and
      other motile processes. New actin-associated proteins are being identified and
      characterized by biochemical means and through isolation of mutants lacking
      individual components. This work is shedding light on the roles of specific actin
      assemblies in various biological processes.

PMID- 8536802
TI  - Transduction of the chemotactic cAMP signal across the plasma membrane of
      Dictyostelium cells.
AB  - Aggregating Dictyostelium cells secrete cAMP during cell aggregation. cAMP
      induces two fast responses, the production of more cAMP (relay) and directed cell
      locomotion (chemotaxis). Extracellular cAMP binds to G-protein-coupled receptors
      leading to the activation of second messenger pathways, including the activation
      of adenylyl cyclase, guanylyl cyclase, phospholipase C and the opening of plasma
      membrane Ca2+ channels. Many genes encoding these sensory transduction proteins
      have been cloned and null mutants of nearly all components have been
      characterized in detail. Undoubtedly, activation of adenylyl cyclase is the most
      complex, involving G-proteins, a soluble protein called CRAC and components of
      the MAP kinase pathway. Null mutants in this pathway do not aggregate, but can
      exhibit chemotaxis and develop normally when supplied with exogenous cAMP. The
      pathways leading to the activation of phospholipase C were identified, but
      unexpectedly, deletion of the phospholipase C gene has no effect on chemotaxis
      and development, nor on intracellular Ins(1,4,5)P3 levels; the metabolism of this
      second messenger will be discussed in some detail. Activation of guanylyl cyclase
      is G-protein-dependent and essential for chemotaxis. Analysis of a collection of
      chemotactic mutants reveals that most mutants are defective in either the
      production or intracellular detection of cGMP, thereby placing this second
      messenger at the center of chemotactic signal transduction. Analysis of the cAMP
      mediated opening of plasma membrane calcium channels in signal transduction
      mutants suggests that it has two components, one that depends on G-proteins and
      intracellular cGMP and one that is G-protein-independent.

PMID- 8536803
TI  - The role of calcium in aggregation and development of Dictyostelium.
AB  - Changes in cytosolic Ca2+ play an important role in a wide array of cell types
      and the control of its concentration depends upon the interplay of many cellular
      constituents. Resting cells maintain cytosolic calcium ([Ca2+]i) at a low level
      in the face of steep gradients of extracellular and sequestered Ca2+. Many
      different signals can provoke the opening of calcium channels in the plasma
      membrane or in intracellular compartments and cause rapid influx of Ca2+ into the
      cytosol and elevation of [Ca2+]i. After such stimulation Ca2+ ATPases located in
      the plasma membrane and in the membranes of intracellular stores rapidly return
      [Ca2+]i to its basal level. Such responses to elevation of [Ca2+]i are a part of
      an important signal transduction mechanism that uses calcium (often via the
      binding protein calmodulin) to mediate a variety of cellular actions responsive
      to outside influences.

PMID- 8536804
TI  - Dual role of cAMP during Dictyostelium development.
AB  - cAMP plays an essential role during Dictyostelium development both outside and
      inside the cell. Membrane-bound receptors and adenylyl cyclase are responsible
      for sensing and producing extracellular cAMP, whereas a phosphodiesterase is
      responsible for maintaining a low basal level. The molecular events underlying
      this type of hormone like signalling, which are now beginning to be deciphered,
      will be presented, in the light of cAMP analogue studies. The importance of
      intracellular cAMP for cell differentiation has been demonstrated by the central
      role of the cAMP dependent protein kinase. Mutants as well as strains obtained by
      reverse genetics will be reviewed which lead to our current understanding of the
      role of intracelluar cAMP in the differentiation of both stalk and spore cells.

PMID- 8536806
TI  - The extracellular matrix of the Dictyostelium discoideum slug.
AB  - In this review, we detail the current understanding of the extracellular matrix
      (ECM) of the migratory slug phase of the cellular slime mould, Dictyostelium
      discoideum. We describe some structural and non-structural molecules which
      comprise the ECM, and how these molecules reflect both plant and animal ECM
      systems. We also describe zones of the multicellular slug that are known to make
      ECM components, including the role of the prestalk cells and the slug epithelium
      like layer. Finally, we review the contributions of studies on mutants to our
      understanding of the ECM of D. discoideum, and relate this to differentiation and
      development in more complex eukaryotic systems.

PMID- 8536805
TI  - Cell adhesion in the life cycle of Dictyostelium.
AB  - Three forms of cell adhesion determine the life cycle of Dictyostelium: i)
      adhesion of bacteria to the surface of the growing amoebae, as the prerequisite
      for phagocytosis; ii) cell-substrate adhesion, necessary for both locomotion of
      the amoebae and migration of the slug; iii) cell-cell adhesion, essential for
      transition from the unicellular to the multicellular stage. Intercellular
      adhesion has received the most attention, and fruitful approaches have been
      developed over the past 25 years to identify, purify and characterize cell
      adhesion molecules. The csA glycoprotein, in particular, which mediates adhesion
      during the aggregation stage, is one of the best defined cell adhesion molecules.
      The molecular components involved in phagocytosis and cell-substratum adhesion
      are less well understood, but the basis has been laid for a systematic
      investigation of both topics in the near future.

PMID- 8536807
TI  - The functional anatomy of memory.
AB  - A review of recent work using Positron Emission Tomography (PET) to examine brain
      systems involved in auditory-verbal memory is presented. Initial work delineated
      widespread brain regions which were, to a large extent, in agreement with
      existing neuropsychological literature. Expanding on this, a number of studies
      have examined memory encoding and retrieval separately. Additionally, experiments
      have been carried out to specifically address sub-components of memory such as
      the use of visual imagery as a mnemonic strategy, the functional anatomical
      evidence for the episodic/semantic memory distinction and the different brain
      regions involved in explicit and implicit memory tasks.

PMID- 8536809
TI  - Localization of prolactin and its receptor messenger RNA in the human decidua.
AB  - Prolactin (PRL) is known as an anterior pituitary hormone. On the other hand, PRL
      is also produced in the human decidualized endometrium. The physiological role
      and site of action of endometrial PRL have not yet been clarified. This study was
      designed to investigate the localization of PRL receptor (PRL-R) gene-expressing
      cells in the human decidualized endometrium using in situ hybridization
      histochemistry. Sense and antisense 35S-labeled RNA probes for human PRL-R mRNA
      were hybridized with cryostat sections of human decidua, which were obtained from
      patients undergoing therapeutic abortion at 8-10 weeks of gestation.
      Hybridization signals for PRL-R mRNA were seen over the decidual cells. No
      labeled cells were seen in the chorion, amnion, or trophoblast. Comparing the
      localization of PRL-R gene-expressing cells to that of PRL gene-expressing cells
      using adjacent sections, their distributions were quite similar. These results
      indicate that not only PRL but also PRL-R transcripts are located in the decidual
      cells.

PMID- 8536808
TI  - Thyroid function parameters during a selenium repletion/depletion study in
      phenylketonuric subjects.
AB  - Phenylketonuric (PKU) subjects have a limited supply of selenium (Se) in their
      phenylalanine-restricted diet. A Se repletion (1 microgram Se/kg/day)/depletion
      study was conducted in PKU children to determine the effect of Se on thyroid
      function parameters. The initial plasma Se concentration (mean +/- SD: 0.26 +/-
      0.12 mumol/L, p < 0.00003, n = 10) and glutathione peroxidase (GSH-Px) activity
      (140 +/- 58 U/L, p < 0.00003, n = 10) were significantly lower compared to age
      matched controls. After 14 weeks of supplementation, the plasma Se concentration
      (mean +/- SD: 0.74 +/- 0.20 mumol/L) normalized (normal range: 0.57-1.15 mumol/L,
      mean +/- SD: 0.76 +/- 0.13 mumol/L, n = 32) and remained stable thereafter during
      repletion. Plasma GSH-Px activity reached normal values after 18 weeks of
      supplementation (312 +/- 57 U/L; normal range: 238-492 U/L, mean +/- SD: 345 +/-
      54 U/L, n = 32) and increased significantly for up to eight weeks thereafter (332
      +/- 52 U/L). Individual and mean thyroid parameters were initially normal in all
      cases. The mean concentrations of plasma thyroxine (T4: p < 0.025), free T4 (FT4:
      p < 0.01) and reverse triiodothyronine (rT3: p < 0.005) decreased to 75% of their
      initial value within three weeks of Se supplementation and remained stable
      thereafter, within a normal physiological range during selenium supplementation.
      They increased back to their initial values three weeks (T4: p < 0.05, FT4: p <
      0.05) and six weeks (rT3: p < 0.025) respectively, after the end of the
      supplementation. In conclusion, Se supplementation modifies thyroid function
      parameters in Se-deficient PKU subjects most likely by an increase in activity of
      type I 5'-deiodinase (5'-DIase I).

PMID- 8536810
TI  - MRI of the foot and ankle: an overview for the referring physician.

PMID- 8536811
TI  - The institutional license.

PMID- 8536812
TI  - Clinical alert--bypass over angioplasty for patients with diabetes.

PMID- 8536813
TI  - Similarities and differences in the properties of substituted benzimidazoles: a
      comparison between pantoprazole and related compounds.
AB  - The novel antiulcer drugs omeprazole, lansoprazole, and pantoprazole are members
      of the class of substituted benzimidazoles. They potently inhibit the gastric
      proton pump by a common mechanism which depends on the acid-induced conversion of
      the parent compounds to the pharmacologically active principles: thiophilic
      cyclic sulfenamides. This transformation takes place in the luminal compartment
      of the secreting parietal cell. However, while the three proton pump inhibitors
      belong to the same chemical class, their two ring systems bear different
      functional substituents. This leads to essential modification of the
      physiochemical, metabolic, and pharmacokinetic properties of these drugs,
      possibly resulting in differences in tissue selectivity and thereby, in the long
      term, drug safety. Both preclinical and clinical data have accumulated that point
      to advantages of pantoprazole related to the above parameters: pantoprazole shows
      a higher stability at moderately acidic pH values and less inhibitory potential
      against cytochrome P450 than the other two drugs. In addition, pantoprazole
      displays linear pharmacokinetics with a high bioavailability.

PMID- 8536814
TI  - Prognosis of gastric carcinoid tumours.
AB  - With the aim of evaluating the prognosis of carcinoid tumours of the stomach, the
      tumours were classified into subtypes on the basis of the type of gastritis, and
      a comparison made of the type of treatment, metastasizing rate, and the survival
      rates of the various groups of patients involved. Of the patients with atrophic
      autoimmune gastritis (type A gastritis) (n = 88) who had multiple carcinoid
      tumours in the corpus or fundus, usually not more than 1 cm in diameter, 98% were
      followed up clinically or by endoscopy and biopsy. In these patients, the
      metastasizing rate was 0%, and the age-corrected Kaplan-Meier survival rate
      revealed normal life expectancy. 25% of the patients with sporadic carcinoid
      tumours (n = 12)--most of whom had a Helicobacter pylori-related gastritis and
      usually solitary tumours located within the corpus of fundus, 25% of which
      exceeding 1 cm in diameter--underwent surgical treatment. In these patients the
      metastasizing rate was 16.7% and the age-corrected survival rate 79%. On the
      basis of our results, we conclude that, depending upon the subtype involved, the
      prognosis of gastric carcinoid tumours varies, such that regular endoscopy/biopsy
      follow-up suffices for patients with type A gastritis, while for patients with
      sporadic carcinoid tumours, surgical treatment is indicated.

PMID- 8536815
TI  - Healing of chronic gastric ulcerations by L-arginine. Role of nitric oxide,
      prostaglandins, gastrin and polyamines.
AB  - This study was designed to determine the efficacy of L-arginine in healing of
      gastric ulcers induced by acetic acid and to assess the role of nitric oxide
      (NO), prostaglandins, gastrin and polyamines in the healing process. Intragastric
      administration of L-arginine (32.5-300 mg/kg/day) enhanced the healing rate of
      these ulcers in a dose-dependent manner, while D-arginine (300 mg/kg/day) was not
      effective. The acceleration of healing by L-arginine was accompanied by a marked
      increase in gastric blood flow (GBF) at the ulcer margin, and an enhancement of
      serum gastrin level, mucosal DNA synthesis, and DNA and RNA contents and
      angiogenesis in the granulation tissue in the ulcer bed. A similar increase in
      ulcer healing associated with hyperemia at the ulcer margin and enhanced
      angiogenesis but without alteration in serum gastrin were observed after
      treatment with glyceryl trinitrate, an NO exogenous supplier. Treatment with NG
      nitro-L-arginine (L-NNA), an inhibitor of NO synthase, delayed ulcer healing and
      this was accompanied by a reduction of GBF at the ulcer margin and in
      angiogenesis in granulation tissue and by a decrease in serum gastrin level and
      mucosal growth. Addition of L-arginine to L-NNA restored ulcer healing, hyperemia
      at the ulcer margin and angiogenesis and prevented the fall in serum gastrin and
      mucosal growth caused by L-NNA. Pretreatment with indomethacin also delayed ulcer
      healing and this was reversed by the coadministration of L-arginine. Inhibition
      of polyamine biosynthesis by difluoro-methyl-ornithine completely abolished the
      acceleration of the healing and the increase in mucosal growth induced by L
      arginine. Our findings indicate that L-arginine accelerates ulcer healing due to
      its hyperemic, angiogenic and growth-promoting actions, possibly involving NO,
      gastrin and polyamines.

PMID- 8536816
TI  - A new gastric ulcer model in rats produced by ferrous iron and ascorbic acid
      injection.
AB  - We developed a new gastric ulcer model in which the ulcers are induced by the
      local injection of a ferrous iron and ascorbic acid (Fe/ASA) solution into the
      gastric wall. These ulcers resemble human gastric ulcers that penetrate the
      muscularis mucosa. The involvement of oxygen radical-mediated lipid peroxidation
      as the cause of these ulcers was investigated. With ferrous iron or ascorbic acid
      alone, gastric ulcers did not form, whereas penetrating ulcers were produced by
      the simultaneous injection of the Fe/ASA solution in a dose-dependent manner.
      Lipid peroxides significantly accumulated in the gastric mucosa from 1 to 24 h
      after the injection of the Fe/ASA solution. This increase in lipid peroxides
      preceded grossly evident gastric ulcer. Treatment with superoxide dismutase (SOD,
      recombinant human CuZnSOD) significantly reduced the size of the ulcers and
      inhibited the accumulation in lipid peroxides in the gastric mucosa, while
      treatment with apo-SOD or heat-inactivated SOD did not. These results suggest
      that lipid peroxidation mediated by oxygen radicals plays a crucial role in the
      pathogenesis of the gastric ulceration induced by the Fe/ASA solution.

PMID- 8536817
TI  - Transcutaneous electrorectography: human electrorectogram from surface
      electrodes.
AB  - The rectal electric activity or electrorectography was recorded transcutaneously
      in 24 healthy volunteers (mean age 39.6 years). A silver-silver chloride
      electrode was applied lateral to each of the two sacroiliac joints, and a third
      one was placed midway between the left greater trochanter and the ischial
      tuberosity. The reference electrode was applied to the right lower limb. At least
      two 20-min recording sessions were performed for each of the 24 subjects. In
      addition, an intrarectal electrorectographic recording was done in 10 of the 24
      subjects using silver-silver chloride electrodes attached to the rectal mucosa by
      suction. Pacesetter potentials (PPs) were recorded transcutaneously. The wave was
      triphasic with a small positive, a large negative and another small positive
      deflection. PPs had a regular rhythm and were reproducible. The mean frequency
      was 3.1 cycles/min. The transcutaneously recorded PPs could be confirmed by the
      intrarectal route. Both routes had similar electrorectographic recordings, except
      for the action potentials (APs) which did not show in the transcutaneous
      electrorectogram. In conclusion, the study demonstrates that PPs could be
      recorded transcutaneously. Transcutaneous electrorectography is simple, easy,
      reproducible and cost-effective, and may prove to be a useful investigative tool
      in the diagnosis of anorectal disorders.

PMID- 8536818
TI  - Gastric emptying of solid food in edentulous patients.
AB  - Whether mastication of food by teeth is a physiological contributor in the
      process of nutrient digestion remains a debatable issue. In this study we sought
      to determine whether mastication could influence the gastric emptying of solid
      food. In 8 edentulous patients, we measured the gastric emptying of a test meal
      ingested with or without their dental prostheses. Clinical dental evaluation and
      Helkimo chewing test were first performed to verify that the mastication
      deficiency was adequately corrected by the dental prostheses. A mixed meal
      containing ten cubes (1.5 cm) of beef liver labeled with 99mTc and mixed in a
      chicken stew was ingested by the subjects and followed by gamma camera external
      scintigraphy. The gastric emptying rate of the 99mTc-labeled liver was similar
      whether the meal was ingested with the denture properly inserted, allowing normal
      mastication of the liver cubes, or whether the food was swallowed unmasticated in
      the absence of functional prostheses (Tlag = 60 +/- 5 vs. 58 +/- 11 min, p = NS;
      T1/2 = 73 +/- 21 vs. 55 +/- 10 min, p = NS; Tlag+T1/2 = 133 +/- 19 vs. 114 +/- 17
      min, p = NS). These results show that gastric trituration and emptying of solid
      food was not facilitated by prior mastication.

PMID- 8536819
TI  - Abnormal esophagocardiac inhibitory reflex in patients with diffuse esophageal
      spasm.
AB  - The aim of this study was to establish if patients with an esophageal dysmotility
      similar to that found in the majority of patients with 'swallow syncope' may also
      have a pathologic esophagocardiac reflex similar to that observed in these
      patients. The effects on heart rate induced by dry and solid swallows and by
      intraesophageal balloon distension were studied in 8 normal subjects and in 10
      patients with diffuse esophageal spasm by simultaneous recording of ECG and
      intraesophageal pressures. Dry swallows induced a brief increase in heart rate,
      while deglutition of a solid bolus initially induced an increase followed by a
      decrease in heart rate, significantly more marked in patients with diffuse spasm.
      The intraesophageal balloon inflation induced a decrease in heart rate which was
      significantly more intense in patients with diffuse spasm. In conclusion, the
      esophageal wall distension either due to solid bolus ingestion or to balloon
      inflation elicits an inhibitory esophagocardiac reflex which is more intense in
      patients with diffuse spasm and might induce cardiac arrhythmias in predisposed
      subjects.

PMID- 8536821
TI  - Intracellular Ca2+ dynamics and in vitro secretory response in acute pancreatitis
      induced by a choline-deficient, ethionine-supplemented diet in mice.
AB  - In order to approach impaired stimulus-secretion coupling in acute pancreatitis
      induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the
      agonist-evoked intracellular Ca2+ dynamics of dispersed pancreatic acini were
      evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h,
      and the pancreas was dispersed to the acini. The in vitro amylase secretion
      analysis of the CDE groups demonstrated a poor dose-response curve which was
      significantly lower (p < 0.01) when 100 pM cholecystokinin (CCK) was
      administered. Both in CDE and control groups, the application of a physiological
      dose of CCK-8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and
      amplitude of the oscillations in the CDE groups were not significantly different.
      The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and
      transient rise in intracellular Ca2+, followed by a small, continuous increase
      above basal levels for the duration of stimulation both in CDE and control
      groups. The peak Ca2+ level was lower in the CDE groups, but this was not
      statistically significant. In conclusion, during the early phase (from 24 to 48
      h) of CDE pancreatitis, the pattern of agonist-evoked intracellular Ca2+ release
      is less affected. Other mechanisms subsequent to the onset of intracellular Ca2+
      release are likely to be involved in the inhibition of enzyme secretion.

PMID- 8536820
TI  - Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the
      endogenous GLP-1 reserve.
AB  - The alpha-glucosidase inhibitor voglibose (AO-128) was designed to prevent rapid
      postprandial blood glucose rises in non-insulin-dependent diabetics. We analyzed
      its effect on the entero-insular axis in 72 healthy volunteers in a double-blind
      study design before, after the 1st dose, and on the 7th day of a 7-day treatment
      protocol (3 daily loads). Six parallel groups of 12 volunteers received voglibose
      (0.5, 1.0, 2.0, or 5.0 mg) or placebo (two groups). Blood was drawn at regular
      intervals up to 180 min after a standardized breakfast to analyze the levels of
      glucose, insulin, C peptide, gastric inhibitory polypeptide, and glucagon-like
      peptide 1 (GLP-1). As expected, after ingestion of voglibose, slight to moderate
      gastro-intestinal discomfort but no severe side-effects were reported. In a dose
      dependent manner, voglibose significantly reduced postprandial increases of blood
      glucose, insulin, and C peptide. At the lower loads (0.5 and 1 mg voglibose three
      times daily), these effects were more pronounced after 7 days. The postprandial
      increase of gastric inhibitory polypeptide was already reduced after the first
      load of 2 and 5 mg voglibose. In comparison to the placebo group, this inhibition
      became also significant for the lower loads after 7 days. Interestingly, GLP-1,
      originating from the lower intestines, was increasingly released under voglibose
      treatment. The first administration of 1 mg voglibose enhanced GLP-1 secretion >
      80% above controls. Treatment with 1 mg voglibose three times daily over 7 days
      revealed a maximal mobilizing effect on endogenous GLP-1 (> 90% above controls)
      which was not further increased by 2- or 5-mg loads. We conclude that voglibose
      treatment effectively inhibits intestinal disaccharidases and thereby mobilizes
      the endogenous pool of insulinotropic GLP-1.

PMID- 8536822
TI  - Effect of enprostil and cimetidine on ethanol-induced damage to intestinal
      epithelial cell lines IRD 98 and IEC 17.
AB  - In addition to their inhibitory action on gastric acid secretion, prostaglandins
      may exert part of their protective effect on the gastrointestinal mucosa by
      specifically maintaining the cellular integrity of the intestinal epithelium.
      This in vitro study investigated the cytoprotective effect conferred on
      intestinal epithelial cell lines IRD 98 and IEC 17 against ethanol injury by the
      synthetic prostaglandin enprostil and compared effects with those of the
      histamine H2-receptor blocker cimetidine. Exposure to 3% ethanol (652 mM) reduced
      cell viability and increased the cAMP and membrane fluidity of both cell lines.
      Our results demonstrate that: (i) enprostil exerts a significant cytoprotective
      effect against damage by ethanol; (ii) cimetidine has no cytoprotective effect;
      (iii) IRD 98 cells are more sensitive to enprostil than IEC 17 cells.

PMID- 8536823
TI  - Activated CD4+ and CD8+ cells in the colonic mucosa of ulcerative colitis
      patients: their relationship to HLA-DR antigen expression on the colonic
      epithelium and serum soluble CD25 levels.
AB  - This study was performed to clarify the relationship between activated (HLA-DR
      expressing) CD4+ and CD8+ cells in the colonic lamina propria of ulcerative
      colitis and other immunological factors, i.e., epithelial DR expression, serum
      soluble CD25 levels, and colonic mucosal CD25+ cells. The frequency of epithelial
      DR expression was positively correlated with the numbers of CD4+ and CD8+ cells.
      The percentages activated CD4+/CD4+ cells were higher in mucosae with DR-
      epithelium than in mucosae with DR+ epithelium. The serum soluble CD25 levels
      were increased in ulcerative colitis, and there was an inverse correlation
      between these levels and the relative number of activated CD4+ cells in untreated
      active disease. These results suggest that interactions among mucosal CD4+ cells,
      colonic epithelium, and serum soluble CD25 might play an important role in the
      pathogenesis of ulcerative colitis.

PMID- 8536824
TI  - Effect of dietary fiber on serum bile acids in patients with chronic cholestatic
      liver disease under ursodeoxycholic acid therapy.
AB  - During ursodeoxycholic acid therapy for chronic cholestatic liver disease, the
      serum levels of lithocholic acid increase about twofold. Lithocholic acid has
      been shown to be hepatotoxic in some animal species. Administration of psyllium
      hydrophilic mucilloid (PHM), a dietary fiber, has been reported to increase the
      bile acid mass excreted by the feces. We, therefore, studied the effect of PHM (3
      x 3.25 g/day) on serum bile acids including lithocholic acid in 12 patients with
      primary sclerosing cholangitis (n = 7) and primary biliary cirrhosis (n = 5)
      receiving ursodeoxycholic acid therapy. After 2 and 6 weeks of treatment with
      PHM, the serum levels of ursodeoxycholic acid increased by 52.4 +/- 72.8% (p <
      0.05) and 40.5 +/- 69.6% (NS), respectively. The absolute serum levels of
      lithocholic acid were not significantly changed. This led to a decrease of the
      relative amount of lithocholic acid as referred to total bile acids and to
      ursodeoxycholic acid in serum by 27.4 +/- 34.5% (p < 0.05) and 25.5 +/- 32.8% (p
      < 0.05), respectively, after 6 weeks of PHM treatment.

PMID- 8536826
TI  - The celiac axis compression syndrome. Report of 5 cases.
AB  - An ongoing debate in the literature discusses whether compression of the celiac
      axis (CA) and/or the superior mesenteric artery (SMA) by the arcuate ligament of
      the diaphragm may be responsible for a clinical syndrome. Five patients with
      postprandial epigastric pain and weight loss, with a loud systolic bruit in the
      epigastric region are described. In 4 cases, no other obvious explanation for the
      complaints was present except compression of the CA and SMA by the arcuate
      ligament of the diaphragm as shown on angiography. One patient had
      cholecystolithiasis. Two patients suffered from thrombosis in the CA with major
      stenosis of the SMA. In 3 cases, solitary stenosis of the CA was present. In 3
      cases, important collateral circulation was seen, and 1 patient had possibly
      ischemic gastric ulcers indicating the ischemic nature of the complaints.
      Vascular reconstruction was done in 4 patients. One patient with a stenosis of
      less than 50% underwent cholecystectomy and was free of complaints thereafter.
      All other 4 patients were free of complaints after the operation. The CA
      compression syndrome should be considered in the differential diagnosis of
      patients with upper abdominal pain, weight loss and a loud systolic bruit in the
      epigastric region.

PMID- 8536825
TI  - Plain X-ray films and air enema films reflect severe mucosal inflammation in
      acute ulcerative colitis.
AB  - In a prospective study of 34 patients with active ulcerative colitis, the
      findings of inflammation on plain abdominal films and air enema films were
      compared to those at colonoscopy including biopsy within 10 days. The degree of
      inflammation on X-ray films was graded independently by two radiologists, at
      colonoscopy by one gastroenterologist and from histological slides from 6
      different colon segments by one pathologist for each patient. Air enema films had
      a high sensitivity for endoscopically confirmed friable or ulcerated mucosa
      (0.91). There was a high specificity (0.86) when excluding inflammation in
      individual colon segments. Absence of fecal residue as an indication of active
      inflammation had the same positive predictive value, 0.95, as an abnormal air
      enema film, 0.98 for endoscopically confirmed inflamed mucosa. The presence of
      fecal residue or a normal air enema film excluded a friable or ulcerated mucosa
      at endoscopy with negative predictive values of 0.83 and 0.86, respectively.
      Patients who had had a complete colonoscopy (n = 16) were divided into groups
      with total, extensive or distal colitis. Air enema films underestimated the
      extent of inflammation in 8 of 16 patients compared to colonoscopy. Of 6 patients
      with distal disease only on air enema films, 5 had disease above the splenic
      flexure at endoscopy. In patients with ulcerative colitis (1) the presence of
      fecal residue and a normal air enema film exclude a friable or ulcerated mucosa
      with a high degree of certainty, and (2) the absence of fecal residue and an
      abnormal air enema film are predictors of the presence of endoscopically
      confirmed inflammation.

PMID- 8536827
TI  - An international glossary for general/family practice.

PMID- 8536828
TI  - Implementation of guidelines on stroke prevention.
AB  - The aim of the present paper was to study the implementation of new medical
      knowledge. We investigated whether Danish doctors have implemented new national
      guidelines for oral anticoagulation of atrial fibrillation. An anonymous
      questionnaire with six standardized case stories was sent to 315 general
      practitioners in the county of Viborg and Ringkobing, 79 heads of departments of
      medicine and cardiology, and 20 heads of departments of neuromedicine across the
      country. The answers showed that the Danish doctors recommended anticoagulant
      therapy only to a low extent for this group of patients despite the guidelines
      and the scientific evidence. The reasons for not choosing anticoagulant therapy
      were lack of knowledge concerning risk of stroke associated with the disease,
      worries about the disadvantages of the treatment, and lack of knowledge of its
      benefits. It is concluded that despite solid scientific documentation and an
      intensive implementation process of guidelines, issued by well-known respected
      colleagues in a small homogeneous country as Denmark (5 million inhabitants),
      knowledge of new research findings varies greatly and is generally limited. To
      obtain optimal use of new research findings, a powerful implementation effort
      must be recommended and the study reveals a need for a closer link between
      research and post-graduate education.

PMID- 8536829
TI  - Depressive disorders in three primary care populations: United States, Israel,
      Japan.
AB  - Primary care patients in the United States, Israel and Japan received the
      Inventory to Diagnose Depression and the Dartmouth COOP Functional Status Charts
      modified for international use. Patients were classified as having major
      depressive disorder or minor depression. Although demographic characteristics
      varied by country, the rank order and frequency of the depressive symptoms were
      similar for both major and minor depression. Functional impairment was most
      severe in patients with major depression, less severe in those with minor
      depression and was least impaired in those not depressed. The results suggest
      that depressive disorders have similar presentations in the three countries
      studied, although the separate cultures confer different consequences on patients
      receiving these diagnoses.

PMID- 8536830
TI  - Predictive value of signs and symptoms for colorectal cancer in patients with
      rectal bleeding in general practice.
AB  - The aim of the study is to determine the diagnostic value of (combinations of)
      signs, symptoms and simple laboratory test results for colorectal cancer in
      patients with rectal bleeding presenting in general practice. Initial complaints
      and findings were compared with the final diagnoses based on clinical follow-up
      after at least 1 year. Patients studied were those presenting overt rectal
      bleeding to the general practitioner (83 GPs in the South of the Netherlands).
      Outcome measures are sensitivity, specificity, predictive values, odds ratios and
      a prediction model derived from multiple logistic regression analysis. Age,
      change in bowel habit and blood mixed with or on stool show a statistically
      significant independent value in the discrimination between patients with a low
      and those with a high probability of colorectal cancer. Many other variables did
      not show predictive value. The prediction model has a sensitivitiy of 100% and a
      specificity of 90%. Although the number of patients with colorectal cancer is
      small (n = 9) it was possible to identify three characteristics which can be
      helpful in the prediction of presence or absence of colorectal cancer in general
      practice. Application of the model presented might prevent 90% of 'unnecessary'
      invasive diagnostic procedures for patients with rectal bleeding who do not have
      colorectal cancer (true negative). Testing the performance of the model in other
      general practice populations is recommended.

PMID- 8536831
TI  - The prevalence of a family history of cancer in general practice.
AB  - The presence of a family history of cancer of the colorectum, breast, uterus and
      ovary is associated with an increased risk for that type of cancer. The aim of
      this study was to assess the prevalence of a family history of these cancers in
      the community. Nurses asked all attenders at health checks aged 35-64 about the
      presence of a history in close relatives of cancer diagnosed under the age of 70.
      Information was obtained from 8109 patients. Of the sample, 3.1% had a family
      history of colorectal cancer; 4.8% of women had a family history of breast
      cancer, whilst 1.9% had a family history of uterine or ovarian cancer. Projecting
      the results to a population of 2000 demonstrated that a general practitioner with
      a list size of 2000 could expect to have 30-40 patients in whom an appropriate
      management strategy would need to be considered.

PMID- 8536832
TI  - The validity of urine examination for urinary tract infections in daily practice.
AB  - For urinary tract infections (UTI), diagnostic testing appears to be reliable and
      simple to perform. This particularly seems to hold true for test strips. In
      studies the validity of several urine tests proved to be high. These studies
      were, however, performed under optimal and standardized conditions. Their results
      therefore do not reflect daily practice. In this study the validity of urine
      tests for UTI is deterined under daily practice conditions, without the use of a
      protocol. The results show a validity considerably lower than under optimal
      conditions. Specificity in particular was lower, even for simple tests like the
      nitrite reaction. Under daily practice conditions, UTI can neither be confirmed
      nor excluded sufficiently on the outcome of a urinary sediment or test strip.

PMID- 8536833
TI  - House calls for respiratory tract infections; family medicine pure and simple?
AB  - House calls still seem to be an important element in the work of general
      practitioners in the Netherlands. A secondary analysis of the data of the
      Netherlands Institute of Primary Health Care (NIVEL) National Study of Illnesses
      and Procedures reveals that 15% of the contacts relating to cases of respiratory
      tract infections are house calls. General practitioners appear to consider
      carefully whether or not to make house calls. House call figures differ
      considerably with respect to diagnosis, reasons for encounter and age. Relatively
      high percentages of house calls occur in cases of lower respiratory tract
      infections, fever as reason for encounter, for old people and young children. The
      number of house calls is hardly associated with region, level of urbanization and
      distance from a hospital. Further research is necessary to establish guidelines
      for the decision whether or not to make a house call.

PMID- 8536834
TI  - Acceptability of shared care for asymptomatic HIV-positive patients.
AB  - In Britain, Human Immunodeficiency Virus (HIV) disease has been seen as an
      illness requiring specialist hospital care at all times. However, as its chronic
      nature has become apparent, the possibiliity that it could be managed more cost
      effectively in primary care has been raised. This has led to increasing interest
      in 'shared care', that is, care which is shared between a general practitioner
      and a specialist according to clear protocols, for this group of patients.
      However, for 'shared care' to be a success, it must be acceptable to all
      concerned: patients, GPs and specialists. This paper presents our experience of
      recruiting asymptomatic HIV-positive patients into a shared care programme: after
      10 months' recruitment only 19 of 128 eligible patients had accepted the offer of
      shared care. The reasons for this, and alternative strategies for increasing GP
      involvement, are discussed.

PMID- 8536835
TI  - Consumer use of multiple general practitioners: an Australian epidemiological
      study.
AB  - The aim of this Australian study was to explore the reasons for peoples' choice
      of general practitioner (GP) in an environment where they have freedom of choice
      of doctor on every occasion of attendance. A questionnaire was administered by
      trained research assistants to 555 people during an hour-long interview.
      Utilization of more than one general practitioner was examined in terms of
      sociodemographic factors, health status and satisfaction with the last general
      practice visit. Respondents were more likely to see more than one general
      practitioner if they had more visits; were dissatisfied with their last
      consultation with a general practitioner; were younger; were female; and were
      highly qualified. Further, respondents who described good communication as the
      rationale for their satisfaction rating for their last general practitioner visit
      were less likely to have seen more than one general practitioner.

PMID- 8536836
TI  - A peer review programme to audit the management of hypertensive patients in
      family practices in Israel.
AB  - We introduced and evaluated a self-audit and peer review programme for the
      management of hypertension in eight urban and rural family medicine practices in
      northern Israel between January 1991 and December 1992. Changes in the level of
      blood pressure control and the effect of peer review and self-audit on
      physicians' management of hypertension were evaluated. Participating physicians
      were provided with feedback throughout the course of the study. Six hundred and
      seventy-four hypertensive patients from a total adult population of 4445 patients
      (15%) were identified in eight practices and followed for two years. The
      percentage of uncontrolled hypertensives (blood pressure > or = to 160/95 mmHg)
      decreased from 46.8% at the beginning of the sstudy to 34.3% at its conclusion (P
      = 0.01). Data on prevalence of hypertension were analysed by participating
      clinics (prevalence range 8.5-24.6%) and by type of community (rural or urban).
      In rural communities 50% of the hypertensives were > or = to 70 years of age,
      compared with 39.5% in the urban practices. Differences in prescribing practices
      among participating physicians were discussed during peer review group meetings
      and changes in prescribed medications for hypertension were evaluated. We
      conclude that this method of self-audit and peer review is effective in improving
      the management of patients with hypertension in family medicine practices. It was
      implemented at a minimal cost, is feasible in busy practices and can be
      generalized to the management of other chronic diseases in the community.

PMID- 8536837
TI  - Change in knowledge of general practitioners during their professional careers.
AB  - In this study the level of knowledge of general practitioners (GPs) in different
      stages of their career, from the undergraduate level onwards to more than 20
      years after certification, has been investigated. The total body of knowledge as
      well as the knowledge about different aspects of care was established.
      Participants were 108 medical students, 445 postgraduate trainees in six
      different stages of their training and 351 GPs with 5 to more than 20 years of
      experience. They all took the same written test, designed to assess knowledge
      closely related to patient care. An increase in test score was found from the
      start of postgraduate training onwards followed by a decrease starting 5-10 years
      after certification. The curves for the different aspects of care varied. It is
      concluded that the body of knowledge of GP-trainees increases during postgraduate
      training and reaches the level of knowledge of GPs who are less than 10 years
      certified. From 10 years after certification onwards the knowledge decreases as
      well as changes over time. The latter had also been found in two American studies
      relating to the knowledge of certified GPs and internists. The results seem
      important for the organization and content of postgraduate training and
      continuous medical education.

PMID- 8536838
TI  - Opening Pandora's box: patients' attitudes towards trainees. Dublin General
      Practice Vocational Training Scheme Third Year Group 1991-1992.
AB  - This study set out to establish patients' attitudes towards GP trainees and to
      determine if patient age, sex, a history of having previously attended a GP
      trainee and practice location affected these attitudes. Two hundred
      questionnaires were distributed to each of the 10 training practices of the 1991
      1992 Dublin GP Vocational Training Scheme. The questionnaires, which were
      completed anonymously, consisted of six statements regarding trainees which were
      answered on a five point Likert scale. A further question enquired about patient
      preference regarding type of doctor for six clinical scenarios. A total of 1510
      completed questionnaires were returned (75%). More than three-quarters of
      patients expect the usual standard of care when seeing a trainee and 91% consider
      it advantageous for a practice to have a trainee. A third consider home visits by
      trainees to be less satisfactory than those performed by the usual doctor. A
      third would not feel as comfortable with the trainee as with their usual doctor
      and 41% would prefer to see their usual doctor after seeing the trainees. Few
      expressed a preference to see the trainee for five out of the six clinical
      scenarios. The exception was consultations regarding gynaecological problems.
      Negative attitudes towards trainees were sigificantly increased amongst urban
      practices, patients over 40 and those who had not previously attended a trainee.
      Patients have definite attitudes towards trainees. These attitudes are negatively
      affected by patient age greater than 40, a history of not previously attending a
      trainee and an urban practice location. These results have implications for the
      training of future general practitioners. How they can be best addressed merits
      further discussion.

PMID- 8536839
TI  - Teaching (and learning) family medicine internationally: a cultural survival
      guide.
AB  - Around the world, family medicine is emerging as an important model for the
      delivery of primary health care services. Clinician-educators from countries with
      successful family medicine programmes will be looked to for leadership in the
      international development of the specialty. Family medicine educators who are
      asked to teach internationally will face numerous challenges as they work to
      adapt their knowledge and expertise to fit local needs. These challenges can
      become either insurmountable obstacles or enriching experiences. The purpose of
      this article is to help guide educators as they explore, enter into and return
      from teaching family medicine abroad. It offers practical suggestions in response
      to three questions important in the course of work abroad: What are one's
      expectations for working abroad? What will one's attitude be toward daily work
      overseas? What will one have learned upon returning home? The suggestions can be
      used to enhance personal and professional development, promote common pathways in
      the development of family medicine as a specialty, and encourage bilateral
      exchange of knowledge and experiences among family physicians worldwide.

PMID- 8536840
TI  - Using focus groups in general practice research.
AB  - Recent years have seen a growing recognition of the appropriateness of
      qualitative methods in family practice. This has been paralleled by an upsurge of
      interest in focus group discussions as a method. Drawing on the experience of
      using focus groups with general practice teams as one component of a multi-method
      study this paper explores emergent orthodoxies regarding the use of focus groups
      and reviews the contribution which this method can make to research in general
      practice.

PMID- 8536841
TI  - Not another questionnaire!: eliciting the views of general practitioners.
AB  - General practitioners have a central role to play in relation to planning and
      delivery of primary and community care services. This paper reports the
      experience of one health board in using a postal survey to ascertain the views of
      local GPs concerning services for people suffering from dementia. The survey was
      sent out once only and had a 41% response rate. Non-responding GPs were surveyed
      to ascertain reasons for failure to respond initially to the survey. The
      commonest reason given was that GPs felt they were being swamped with
      questionnaires. The paper discusses the problems of accessig GP opinion when time
      and resources are limited, the alternative strategies that could have been
      employed and the way forward in the light of the experience.

PMID- 8536843
TI  - An international glossary for general/family practice. WONCA Classification
      Committee.

PMID- 8536842
TI  - Family practice in Turkey.
AB  - Family practice is a very new medical specialty in Turkey. Family practice
      residency programmes have been attended since 1985 only in state hospitals and in
      1995 departments of family practice will be funded in universities, too. In this
      article, we review the problems of family practice in Turkey and we mention our
      own opinions and comments about various aspects of it.

PMID- 8536844
TI  - Frequent attenders.

PMID- 8536845
TI  - A prospective study of the epidemiology of colitis and colon cancer in cotton-top
      tamarins (Saguinus oedipus).
AB  - BACKGROUND & AIMS: Spontaneous colitis and colon cancer in the cotton-top tamarin
      have been shown to resemble human ulcerative colitis and its associated cancer.
      The effect of environment and diet on the evolution of the disease was studied in
      animals from birth to 5 years of age. METHODS: Newborn tamarins were assigned to
      three groups reared in (1) a colony in which colitis was highly prevalent and fed
      a standard diet; (2) an isolation unit and fed a standard diet or one of two
      semipurified diets; and (3) a multispecies nursery, returned to the colony, and
      fed the same semipurified diets. Mucosal biopsy specimens from the descending
      colon were taken at 4-month intervals. RESULTS: Acute colitis and chronic mucosal
      changes were significantly higher in the colony than in the isolation unit. Diet
      had no effect on acute colitis, but chronic mucosal changes were significantly
      higher in animals fed a standard diet than semipurified diets. CONCLUSIONS: Data
      suggest that acute colitis was associated with environment. Factors in the
      environment, including a transmissible agent, are discussed. Chronic mucosal
      changes were modified by diet. Cancer was associated with acute colitis and
      chronic changes and seems to be associated with diet.

PMID- 8536846
TI  - Comparison of resistant starch with cellulose diet on 1,2-dimethylhydrazine
      induced colonic carcinogenesis in rats.
AB  - BACKGROUND & AIMS: Epidemiological and experimental studies have shown that
      dietary fiber may prevent colon cancer. Resistant starch, like dietary fiber, is
      not subject to digestion in the small intestine. However, it is unknown whether
      resistant starch inhibits colonic carcinogenesis. In vitro studies have shown
      that butyrate slows the growth of cultured colon cancer cells. The effect of
      resistant starch diet on 1,2-dimethylhydrazine-induced colonic carcinogenesis in
      rats was evaluated, and the colonic butyrate concentration was measured. METHODS:
      Sprague-Dawley rats were randomly divided into five groups that were fed diets
      containing no fiber, 3% cellulose, 10% cellulose, 3% resistant starch, or 10%
      resistant starch. Colonic carcinogenesis and butyrate concentration of colonic
      contents and feces in each diet group were compared. RESULTS: Total cancer volume
      per rat in the 10% cellulose group was significantly lower than that in the basal
      group (109 +/- 54 mm3 and 247 +/- 83 mm3; P < 0.05), but the other groups showed
      no significant differences. The butyrate concentration in colonic content and in
      feces were higher in the resistant starch groups than in the cellulose groups.
      CONCLUSIONS: The resistant starch diet increased butyrate concentration but did
      not inhibit colonic carcinogenesis. It remains doubtful whether butyrate inhibits
      the proliferation of colon cancer cells.

PMID- 8536847
TI  - Consumption of onions and a reduced risk of stomach carcinoma.
AB  - BACKGROUND & AIMS: Results from case-control studies and laboratory tests
      indicate that consumption of allium vegetables may considerably reduce the risk
      of stomach cancer. The association between onion and leek consumption, garlic
      supplement use, and the incidence of stomach carcinoma was studied. METHODS: The
      association was investigated in the Netherlands Cohort Study on diet and cancer,
      which started in 1986 with 120,852 men and women ranging in age from 55 to 69
      years. Dietary data were available for 139 stomach carcinoma cases diagnosed
      during 3.3 years of follow-up and for 3123 subjects of the randomly selected
      subcohort. RESULTS: The rate ratio for stomach carcinoma in the highest onion
      consumption category (> or = 0.5 onions/day) was 0.50 (95% confidence interval,
      0.26-0.95) compared with the lowest category (0 onions/day) after adjustment for
      other risk factors. The reduction in risk was restricted to carcinoma in the
      noncardia part of the stomach (P = 0.002) and was also found among subjects
      without a history of stomach disorders (P = 0.01). The consumption of leeks and
      the use of garlic supplements were not associated with stomach carcinoma risk.
      CONCLUSIONS: The Netherlands Cohort Study provides evidence for a strong inverse
      association between onion consumption and stomach carcinoma incidence.

PMID- 8536848
TI  - Mast cells mediate acid-induced augmentation of opossum esophageal blood flow via
      histamine and nitric oxide.
AB  - BACKGROUND & AIMS: Increased esophageal blood flow during reflux episodes may
      play an important role in mucosal resistance to injury, although the mechanism
      remains unclear. Decreased stainable mast cells and increased luminal histamine
      release during acid exposure has been previously documented. Therefore, the role
      of mast cells, nerves, histamine, and nitric oxide in mediating increased blood
      flow during acid challenge of the distal esophagus was investigated. METHODS: The
      effects of the mast cell stabilizers disodium cromoglycate and doxantrazole, the
      neurotoxin tetrodotoxin, the histamine H1 receptor antagonist promethazine, and
      the NO synthase inhibitor N omega-nitro-L-arginine methyl ester were examined by
      monitoring opossum esophageal histamine release and blood flow during perfusion
      with 100 mmol/L HCl. RESULTS: Luminal acid challenge significantly increased both
      histamine release and blood flow (P < 0.05). Disodium cromoglycate, promethazine,
      and N omega-nitro-L-arginine methyl ester attenuated the increase in blood flow
      to basal (saline-perfused) levels. Tetrodotoxin did not prevent an acute increase
      in blood flow that rapidly returned to baseline, likely from the ensuing
      hypotension. CONCLUSIONS: These findings provide evidence that mast cell-derived
      histamine, acting through an NO-dependent mechanism, plays a central role in the
      response of the esophageal microcirculation to luminal acid.

PMID- 8536849
TI  - Prostaglandin E2 modulates neurally induced nonadrenergic, noncholinergic gastric
      relaxations in the rabbit in vivo.
AB  - BACKGROUND & AIMS: Prostaglandin (PG) E2 has been shown to modulate adrenergic
      and cholinergic neurotransmission in the gut. This study investigated PGE2
      influence on vagally induced, nonadrenergic, noncholinergic (NANC) gastric
      relaxations. METHODS: Mechanical activity of the stomach was recorded in
      anesthetized rabbits. RESULTS: In atropine-treated animals, electrical vagal
      stimulation or arterial bolus injection of the ganglion stimulant dimethyl
      phenylpiperazinium iodide (DMPP) evoked inhibitory responses that varied from a
      brisk relaxation, interrupted by a poststimulus excitatory motility (biphasic
      response), to a long-lasting relaxation (monophasic response). PGE2 reduced and,
      at the highest doses, abolished the neurally induced relaxant responses elicited
      either by vagal stimulation or DMPP administration but did not affect the gastric
      relaxation caused by adenosine triphosphate (ATP), sodium nitroprusside (SNP), or
      vasoactive intestinal polypeptide (VIP). ATP or 2-methylthioadenosine
      triphosphate (2-MeSATP) reduced and then suppressed vagally induced inhibitory
      motility; the relaxant responses elicited by SNP, VIP, and ATP itself were not
      influenced. After administration of the prostaglandin synthesis inhibitor
      suprofen, ATP and 2-MeSATP failed to block vagally induced inhibitory responses.
      Arterial infusion of adenosine at the highest rates did not influence the
      amplitude of the vagally induced relaxant responses. Following theophylline
      administration, ATP still blocked the relaxation elicited by vagal stimulation.
      CONCLUSIONS: PGE2 may modulate NANC inhibitory neurotransmission in the stomach.
      The effects of ATP on the neurally induced NANC gastric relaxation may be caused
      by PGE2.

PMID- 8536850
TI  - The effect of intrathecal opioid-receptor agonists on visceral noxious
      stimulation in rabbits.
AB  - BACKGROUND & AIMS: Conflicting results have been published concerning the effects
      of different opioid-receptor agonists against visceral noxious stimulation. The
      introduction of colorectal distention facilitates research in this field. The aim
      of this study was to examine intrathecally administered opioid agonists against
      colorectal distention in conscious rabbits. METHODS: Rabbits were equipped with a
      subcutaneous intrathecal injection system. Colorectal distention was induced by
      inflation of a balloon inserted into the descending colon. The test parameter was
      the pressure eliciting a characteristic visceromotor response. Examinations were
      performed before and after administration of the following drugs: morphine,
      U50488H, [D-Pen2, D-Pen5]enkephalin (DPDPE), naloxone, MR2266, naltrindole,
      saline, and acidified saline. RESULTS: The visceromotor response to colorectal
      distention was inhibited in a dose-dependent fashion by intrathecal opioids
      acting as agonists at all three types of opioid receptors. Morphine was
      antagonized more effectively by intrathecal than intramuscular naloxone. U50488H
      and DPDPE were equally antagonized by the specific antagonists MR2266 and
      naltrindole. Electrical thresholds in the lumbar region were increased, although
      they remained unaltered in the cervical region after administration of all three
      agonists. CONCLUSIONS: Intrathecal administration of different opioid agonists
      produces a dose-dependent spinal effect. The rank order of potencies in this
      model is DPDPE > U50488H > morphine > saline = 0.

PMID- 8536851
TI  - Gastrin secretion from primary cultures of rabbit antral G cells: stimulation by
      inflammatory cytokines.
AB  - BACKGROUND & AIMS: In Helicobacter pylori-induced gastritis, local production of
      cytokines may favor hypergastrinemia as an endocrine link between H. pylori
      induced gastritis and duodenal ulcer. The aim of this study was to characterize
      cytokine effects on cultured rabbit antral G cells. METHODS: Monolayers (14.2% +/
      2.9% G cells) were studied after 48 hours in primary culture. RESULTS:
      Interleukin (IL) 1 beta (50% effective concentration [EC50], 5.3 +/- 0.4 ng/mL)
      and tumor necrosis factor (TNF) alpha (EC50, 5.5 +/- 0.5 ng/mL) stimulated
      gastrin release to 50% of the maximal response to 10(-9) mol/L neuromedin C.
      Stimulation by the maximally effective concentration of IL-1 beta (10 ng/mL) was
      inhibited by the human IL-1 receptor antagonist (100 ng/mL; inhibitory constant,
      23.0 ng/mL), which prefers type I over type II IL-1 receptors. The response to
      the maximally effective concentration of TNF-alpha (10 ng/mL) was markedly
      inhibited by monoclonal antibody H398, an antagonist at TNF P55 receptors
      (inhibitory constant, 1.7 micrograms/mL), whereas monoclonal antibody utr1, an
      antagonist at TNF P75 receptors, was ineffective. Stimulation by IL-1 beta and
      TNF-alpha was additive to the responses to neuromedin C and O2-dibutyryl
      adenosine 3',5'-cyclic monophosphate. IL-6 and IL-8 (0.1-50 ng/mL) were
      ineffective. CONCLUSIONS: IL-1 beta and TNF-alpha stimulate gastrin secretion via
      receptors potentially residing on rabbit antral G cells themselves. We speculate
      that G cells express type I IL-1 receptors and TNF P55 but not TNF P75 receptors.

PMID- 8536852
TI  - Hypertrophic gastropathy in Helicobacter felis-infected wild-type C57BL/6 mice
      and p53 hemizygous transgenic mice.
AB  - BACKGROUND & AIMS: Helicobacter pylori infection causes gastritis and peptic
      ulcers and is linked epidemiologically to gastric cancer. To analyze host genetic
      factors and the influence of Helicobacter on cell proliferation, we used an
      inbred and p53 hemizygous mouse model of Helicobacter felis-induced gastritis.
      METHODS: H. felis was inoculated by gastric intubation into SPF C57BL/6 wild-type
      and p53 hemizygous mice that were followed up for 1 year and compared with
      uninfected controls of the same genotype using histology, proliferating cell
      nuclear antigen (PCNA) staining, and 5-bromo-2'-deoxyuridine (BrdU) analysis.
      RESULTS: Infected animalls developed sustained anti-H. felis serum immunoglobulin
      G antibody responses. Six months after infection, both wild-type and p53
      hemizygous mice showed active chronic inflammation and marked mucosal hyperplasia
      compared with uninfected controls. One year after infection with H. felis, the
      wild-type and p53 hemizygous mice showed severe adenomatous and cystic
      hyperplasia of the surface foveolar epithelium. BrdU uptake and PCNA staining
      were markedly increased in both sets of infected mice compared with controls.
      Infected p53 hemizygous mice had a higher proliferative index than the infected
      wild-type mice. CONCLUSIONS: H. felis can induce a hypertrophic gastropathy in
      the C57BL/6 genotype; loss of one p53 allele, although insufficient to initiate
      carcinogenesis at 1 year, enhances the proliferative index, which may lead to an
      increased risk of cancer induction.

PMID- 8536853
TI  - A longitudinal analysis of hepatitis C virus replication following liver
      transplantation.
AB  - BACKGROUND & AIMS: The pathogenesis of graft injury in liver transplant
      recipients with recurrent hepatitis C virus (HCV) infection remains poorly
      understood. In this study, the relationship between HCV replication, genotype,
      and the evolution of graft damage was investigated. METHODS: HCV RNA was
      quantified in 184 protocol sera from 25 patients transplanted for HCV cirrhosis.
      HCV isolates were genotyped, and hepatic expression of core and NS4 antigens was
      sought in protocol allograft biopsy specimens. RESULTS: Acute lobular hepatitis
      was accompanied by a steep increase in HCV RNA levels and the appearance of core
      and NS4 antigens in the graft. Methylprednisolone treatment for acute rejection
      led to a 4-100-fold increase in serum HCV RNA. At the end of follow-up, HCV RNA
      levels were 3-112 times pretransplant levels and were higher in patients with
      more severe hepatitis. Progressive liver damage developed in 7 of 14 patients
      with HCV genotype 1b and in 1 of 11 patients infected with other genotypes (P =
      0.03). CONCLUSIONS: Peak viremia levels and the initial detection of HCV antigens
      in hepatocytes suggests increased viral replication at the time of acute HCV
      hepatitis in the graft. Genotype 1b and higher viremia levels were associated
      with more severe chronic graft damage.

PMID- 8536854
TI  - Influence of different hepatitis C virus genotypes on the course of asymptomatic
      hepatitis C virus infection.
AB  - BACKGROUND & AIMS: The association of liver disease with hepatitis C virus (HCV)
      genotypes mainly refers to patients with serious liver damage; little information
      is available on symptomless carriers. The aim of this study was to investigate
      the correlation of genotypes with clinical course, risk factors for infection,
      and antibody to HCV reactivity in asymptomatic subjects. METHODS: One hundred
      nine viremic blood donors with at least 1 year of follow-up were studied; 41
      underwent liver biopsy. Genotypes were determined by line-probe assay. RESULTS:
      Genotype 1 was found in 47 (43.1%), genotype 2 in 48 (44%), genotype 3 in 8
      (7.3%), genotype 4 in 2 (1.8%), and coinfections in 4 (3.7%). The relative risk
      (RR) for a raised pattern of alanine aminotransferase, aspartate
      aminotransferase, and gamma-glutamyltranspeptidase was 2.1 (confidence interval
      [CI], 1.4-3.2), 1.7 (CI, 1.2-2.4), and 2.8 (CI, 1.6-4.9) in subjects with
      genotype 1 vs. 0.4 (CI, 0.2-0.7), 0.4 (CI, 0.3-0.7), and 0.4 (CI, 0.2-0.8) in
      subjects with genotype 2. Chronic hepatitis was found in 68%; the RR of chronic
      hepatitis was similar for genotypes 1 and 2 (RR, 1.1 [CI, 0.8-1.7] vs. RR, 1.0
      [CI, 0.7-1.6]). Reactivity to NS4-derived antigens was infrequent in type 2
      infected subjects. CONCLUSIONS: Genotype 2 was as frequent as genotype 1 but
      associated with less liver function impairment. The high prevalence of chronic
      hepatitis should be considered in counseling viremic asymptomatic donors.

PMID- 8536855
TI  - Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma: association
      with elevated alpha-fetoprotein production.
AB  - BACKGROUND & AIMS: In human hepatocellular carcinoma, restriction fragment length
      polymorphism analysis has shown frequent allelic loss on chromosomes 4q and 16q.
      To better define the commonly affected region for further positional cloning of
      the putative tumor-suppressor genes contained in these two chromosome arms,
      microsatellite polymorphism analysis was conducted to analyze extensively the
      allelic loss on both chromosome loci. METHODS: DNA from 42 pairs of large
      hepatocellular carcinoma (> 5 cm) and corresponding nonneoplastic liver tissues
      were prepared. Allelic loss on chromosome 4q and 16q was investigated by 13 or 12
      sets of microsatellite polymorphic markers. RESULTS: The frequency of allelic
      loss on chromosome 16q was 70%, and the common region was mapped to 16q22-23. An
      even higher frequency (77%) was found on chromosome 4q with the common region
      mapped to 4q12-23. The allelic loss of chromosome 4q was significantly associated
      with hepatocellular carcinoma of elevated serum alpha-fetoprotein but not with
      those of normal level (91% vs. 30%; Fisher's Exact Test, two-tailed P = 1.12 x
      10(-4)). CONCLUSIONS: The results form the basis for further positional cloning
      of putative tumor-suppressor genes on chromosome 4q and 16q. Moreover, the one on
      chromosome 4q might shed light on the mechanism of alpha-fetoprotein expression
      in hepatocellular carcinoma.

PMID- 8536856
TI  - The role of central blood volume in the development of sodium retention in portal
      hypertensive rats.
AB  - BACKGROUND & AIMS: In portal hypertension, peripheral vasodilatation (PVD) causes
      Na+ retention as a result of vascular underfilling. The central blood volume is
      responsible for the vascular filling signals to baroreceptors and volume
      receptors. The aim of this study was to determine the role of central blood
      volume in Na+ retention in portal hypertensive rats. METHODS: Mean arterial
      pressure, portal pressure, cardiac output, total peripheral resistance, central
      blood volume, and extracellular Na+ space were assessed daily in rats after
      portal vein ligation or sham operation until a hyperdynamic circulatory state
      developed. RESULTS: On day 1, portal vein-ligated rats had PVD and a diminished
      central blood volume (1.26 +/- 0.04 vs. 1.47 +/- 0.09 mL/100 g body wt; P <
      0.05). On day 2, Na+ space increased in portal vein-ligated rats (38.1 +/- 0.5
      vs. 33.1 +/- 0.5 mL/100 g body wt; P < 0.01). From day 2 on, normalization of
      central blood volume and cessation of Na+ retention were observed despite
      persistent PVD. On day 4, portal vein-ligated rats developed a hyperdynamic
      circulatory state with a normal central blood volume and persistent PVD.
      CONCLUSIONS: Although total peripheral resistance remains decreased, Na+
      retention ceases after central blood volume is normalized. Central blood volume
      therefore appears to be the signal for Na+ retention. Although PVD persists after
      Na+ retention ceases, it may contribute to Na+ retention by decreasing central
      blood volume.

PMID- 8536857
TI  - Down-regulation of expression and function of the rat liver Na+/bile acid
      cotransporter in extrahepatic cholestasis.
AB  - BACKGROUND & AIMS: The molecular regulation of hepatic bile acid transporters
      during cholestasis is largely unknown. Cloning of complementary DNAs for the
      sinusoidal sodium-dependent taurocholate cotransporting polypeptide (ntcp), the
      cytosolic bile acid-binding protein 3 alpha-hydroxysteroid dehydrogenase (3 alpha
      HSD), and a putative canalicular bile acid transporter Ca2+, Mg(2+)-ecto
      adenosine triphosphatase, now facilitates such studies. METHODS: Protein mass,
      steady-state messenger RNA (mRNA) levels, and gene transcription were assessed in
      rat livers after common bile duct ligation (CBDL) from 1-7 days, and taurocholate
      uptake was determined in isolated hepatocytes. RESULTS: After CBDL, Na(+)
      dependent taurocholate uptake (Vmax) declined by 70%. The levels of ntcp protein
      were reduced by more than 90%, and 3 alpha-HSD levels decreased by 66% by 7 days.
      Expression and canalicular localization of the ecto-adenosine triphosphatase
      remained unchanged. mRNA levels for both ntcp and 3 alpha-HSD diminished by about
      60% 1 day after CBDL and remained unchanged up to 7 days. Transcriptional
      activity was decreased 1 day after CBDL only for ntcp. CONCLUSIONS: Extrahepatic
      cholestasis results in rapid down-regulation of Na(+)-dependent taurocholate
      uptake, ntcp transcription, and posttranscriptional regulation of both ntcp and 3
      alpha-HSD mRNA. This selective decline of ntcp may represent a protective
      feedback mechanism in cholestasis to diminish uptake of potentially hepatotoxic
      bile acids.

PMID- 8536858
TI  - Extract of Helicobacter pylori induces neutrophils to injure endothelial cells
      and contains antielastase activity.
AB  - BACKGROUND & AIMS: Previous studies indicate that a water extract of Helicobacter
      pylori promotes leukocyte adhesion and emigration as well as endothelial barrier
      disruption (increased vascular protein leakage) in rat mesenteric venules. The
      aims of this study were to assess whether H. pylori extract-activated neutrophils
      disrupt endothelial cell monolayers and to identify the mechanisms involved in
      this process. METHODS: Human neutrophils were incubated with monolayers of human
      umbilical vein endothelial cells (HUVECs) in the presence or absence of H. pylori
      extract. RESULTS: H. pylori extract-activated human neutrophils produced
      endothelial cell detachment from HUVEC monolayers, the severity of which was
      dependent on the duration of exposure. Endothelial cell detachment was prevented
      by a monoclonal antibody directed against CD11/CD18 on neutrophils or a
      monoclonal antibody against intercellular adhesion molecule 1 on endothelial
      cells. HUVEC monolayer disruption was also prevented by superoxide dismutase,
      catalase, and a monoclonal antibody against elastase. Further studies indicated
      that H. pylori extract was capable of inhibiting human neutrophil elastase. The
      antielastase activity was not diminished by oxidants. CONCLUSIONS: These studies
      indicate that H. pylori extract-activated human neutrophils can disrupt HUVEC
      monolayers only when human neutrophils are allowed to adhere to HUVECs and may
      provide an explanation for the H. pylori extract-induced, neutrophil-dependent
      vascular protein leakage observed in vivo. The possibility that H. pylori
      releases antiproteases may explain, in part, why this bacterium is so virulent.

PMID- 8536859
TI  - Cell-generated nitric oxide inactivates rat hepatocyte mitochondria in vitro but
      reacts with hemoglobin in vivo.
AB  - BACKGROUND & AIMS: Nitric oxide forms inactive iron-nitrosyl complexes within
      hepatic mitochondria in vitro. However, when formed in vivo, NO might react
      instead with hemoglobin. The aim of this study was to compare the effects of cell
      derived NO on rat hepatocyte mitochondria in vitro and in vivo. METHODS: First,
      hepatocytes were cultured in vitro for 24 hours under a porous membrane
      supporting macrophages that were stimulated by endotoxin. Second, hepatic
      macrophage hyperplasia was induced in vivo by preadministration of killed
      Corynebacterium parvum; 7 days later, rats received endotoxin and were killed
      after 6 hours. Third, mitochondria were exposed to sodium nitroprusside in vitro,
      washed, mixed with blood, and recovered. RESULTS: Iron-nitrosyl complexes and
      hepatocyte mitochondrial dysfunction were observed in the in vitro model and
      prevented by an NO synthase inhibitor. In the in vivo model, however, despite a
      130-fold increase in plasma nitrate levels and formation of hemoglobin-NO
      complexes in blood, no iron-nitrosyl complex was detected in hepatic
      mitochondria, and hepatic mitochondrial function was not impaired. In the third
      model, mitochondria lost preformed iron-nitrosyl complexes when exposed to blood.
      CONCLUSIONS: Although NO reacts with hepatocyte mitochondria in vitro, in vivo it
      reacts with sinusoidal hemoglobin without detectable impairment of hepatic
      mitochondrial function.

PMID- 8536861
TI  - Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas
      without pancreatic disease.
AB  - BACKGROUND & AIMS: We and others have previously shown that the mutation of K-ras
      codon 12 was found in the majority of pancreatic adenocarcinomas. The mutation
      has also been identified in the pancreatic duct with mucous cell hyperplasia in
      association with chronic pancreatitis. Ductal hyperplasia is also frequently
      found in the pancreas free from pancreatic carcinoma or chronic pancreatitis. The
      aim of this study was to assess the incidence and types of mutations in
      hyperplastic foci in these cases. METHODS: The nucleotide sequence of the K-ras
      gene at codon 12 of the DNA extracted from microdissected hyperplastic epithelium
      of the pancreatic duct obtained at autopsy in patients without pancreatic
      adenocarcinoma or chronic pancreatitis was analyzed. RESULTS: Of 38 patients with
      79 hyperplastic foci, 12 patients (with 19 hyperplastic foci) had mutations. None
      of the 16 normal ducts in 12 specimens had this mutation. The nucleotide sequence
      of the codon in 53% of ductal hyperplastic foci was TGT or AGT, both of which
      were not found in 30 cases of adenocarcinoma. CONCLUSIONS: These results suggest
      that the ras gene mutation occurs frequently in multifocal hyperplastic foci of
      pancreatic duct and that the mutations may not have direct relevance to the
      carcinogenesis of pancreatic cancer.

PMID- 8536860
TI  - Analysis of Ki-ras codon 12 mutations in the duodenal juice of patients with
      pancreatic cancer.
AB  - BACKGROUND & AIMS: Point mutations of the Ki-ras gene at codon 12 have been
      frequently identified in pure pancreatic juice of patients with pancreatic cancer
      in studies examining pancreatic cancer tissues. The aim of this study was to
      examine mutations of the Ki-ras codon 12 in the duodenal juice collected from
      patients with various pancreatic disorders. METHODS: The duodenal juice was
      collected through a Dreiling tube installed in the duodenum during a secretin
      test. Analysis of the Ki-ras mutations was performed using the enriched
      polymerase chain reaction--single-strand conformation polymorphism technique.
      RESULTS: Point mutations were detected in 12 of 19 patients with pancreatic
      cancer; of the 12 patients, 10 had ductal tubular adenocarcinoma and 2
      intraductal papillary adenocarcinoma. Mutational patterns included GAT (n = 4),
      GTT (n = 3), CGT (n = 1), and double mutations of GTT and GAT (n = 3) and GAT and
      CGT (n = 1). In 41 patients with benign pancreatic disorders, a point mutation
      was detected in only 1 patient with chronic pancreatitis. CONCLUSIONS: Analysis
      of the Ki-ras codon 12 mutations in the duodenal juice is useful in the diagnosis
      of pancreatic cancer.

PMID- 8536862
TI  - Antibiotic treatment improves survival in experimental acute necrotizing
      pancreatitis.
AB  - BACKGROUND & AIMS: It is still unproven whether prophylactic antibiotics can
      reduce mortality from acute necrotizing pancreatitis (ANP). The aim of this study
      was to investigate whether antibiotic therapy can influence long-term outcome in
      ANP and how appropriate this therapy is. METHODS: ANP was induced in rats by
      standardized intraductal bile acid infusion and cerulein hyperstimulation. Serum
      trypsinogen activation peptide levels were used to verify comparable disease
      severity. Starting 6 hours after induction, animals randomly received saline (n =
      60), 20 mg/kg imipenem (n = 62), or 10 mg/kg ciprofloxacin (n = 60) every 8 hours
      for 7 days. On day 7, half of each group was killed so a quantitative pancreatic
      bacteriology could be conducted. The other half was analyzed at 21 days for long
      term mortality, late bacteriologic changes, abscesses, and pseudocysts. RESULTS:
      Comparable trypsinogen activation peptide increases confirmed equally severe ANP
      in each group before treatment. Imipenem and ciprofloxacin significantly reduced
      the number of infected pancreatic specimens, bacterial counts, and identified
      species at 1 week. At 3 weeks, pancreatic infection prevalence was lower in
      animals treated with antibiotics; abscess formation was reduced and pseudocysts
      were smaller and less frequently infected. Survival was significantly improved by
      imipenem and ciprofloxacin. CONCLUSIONS: Antibiotic treatment reduces early and
      late septic pancreatic complications and improves survival from experimental ANP.

PMID- 8536863
TI  - Effect of nonpeptide motilin agonist EM523 on release of gut and pancreatic
      hormones in conscious dogs.
AB  - BACKGROUND & AIMS: EM523, a nonpeptide motilin agonist, is being developed for
      clinical use to improve delayed gastric emptying. The aim of this study was to
      examine the effect of EM523 on endogenous release of gut and pancreatic hormones
      in conscious dogs. METHODS: Motility of the gastrointestinal tract was monitored
      using force transducers. Blood concentrations of gut and pancreatic hormones were
      measured using a specific radioimmunoassay. EM523 (3 micrograms/kg) or normal
      saline (5 mL) was given during the phase I period of the interdigestive state.
      RESULTS: A single injection of EM523 always induced phase III-like contractions
      in the intact gastric antrum and was accompanied by significant (P < 0.01)
      release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin,
      cholecystokinin, and secretin were not released by EM523. The significant release
      of these hormones was suppressed by pretreatment with atropine and completely
      eliminated by a 5-hydroxytryptamine 3 receptor antagonist and truncal vagotomy.
      CONCLUSIONS: The findings suggest that EM523 stimulates the release of pancreatic
      polypeptide, insulin, and motilin by activating the cholinergic parasympathetic
      nerve system, finally stimulating the endocrine pancreas through vagally
      cholinergic muscarinic receptors in the pancreatic islets. The participation of 5
      hydroxytryptamine 3 receptors in this system is strongly suggested by the
      results.

PMID- 8536864
TI  - The potential site of impaired gallbladder contractility in an animal model of
      cholesterol gallstone disease.
AB  - BACKGROUND & AIMS: Gallbladder contractility is decreased in cholesterol
      gallstone disease, but the mechanism underlining this defect is unclear. The aim
      of this study was to determine the cellular site of this defect in an animal
      model of cholesterol gallstone disease. METHODS: Ground squirrels were maintained
      for 28 days on either a control or a 1% cholesterol diet. Gallbladder contractile
      responses to several known agonists were measured in vitro using smooth muscle
      strips. RESULTS: Gallbladder contractility in response to cholecystokinin,
      bethanechol, and K+ was equally decreased in cholesterol-fed animals, in concert
      with an increased cholesterol saturation of gallbladder bile compared with
      controls. In contrast, the contractile responses to A-23187 (a calcium
      ionophore), cyclopiazonic acid (a selective, potent inhibitor of sarcoplasmic
      reticulum Ca2+ pump), and barium (a calcium analogue), which readily diffuse
      across the intact sarcolemmal membrane, remained the same in both groups. Dose
      responses to a G-protein activator, aluminum fluoride, were again not different
      between these two groups. CONCLUSIONS: The primary smooth muscle defect in this
      animal model of cholesterol gallstone disease does not reside in the
      intracellular signal transduction pathways or in the contractile apparatus but
      instead involves the sarcolemmal membrane.

PMID- 8536865
TI  - Gastric toxoplasmosis in acquired immunodeficiency syndrome: antemortem diagnosis
      with histopathologic characterization.
AB  - Gastrointestinal symptoms attributable to Toxoplasma gondii infection are
      distinctly unusual, and antemortem diagnosis of gastrointestinal involvement is
      rarely documented, particularly in the absence of cerebral manifestations or
      disseminated disease. This case report describes a rare example of T. gondii
      infection of the stomach diagnosed antemortem in a 22-year-old Haitian woman with
      acquired immunodeficiency syndrome (AIDS) who presented with fever and abdominal
      pain. An abdominal computerized tomographic scan showed thickened gastric walls.
      Endoscopy showed diffusely thickened gastric folds and a fundic ulcer along the
      greater curvature. Light and electron-microscopic examination of gastric mucosal
      biopsy specimens showed active Toxoplasma infection with necrosis and
      intracellular trophozoites within the gastric epithelium, smooth muscle cells,
      macrophages, and endothelial cells. Both true cysts and pseudocysts were seen.
      Disseminated disease was documented by the growth of T. gondii in a tissue
      culture from a venous blood sample. It is concluded that some patients with AIDS,
      particularly those from areas endemic for Toxoplasma infection, can manifest
      disseminated disease in unusual locations such as the gastrointestinal tract.
      Documentation of active T. gondii infection based on tissue cultures of venous
      blood or on biopsy specimens of symptomatic extracerebral sites can lead to a
      rapid diagnosis of toxoplasmosis, a treatable disease.

PMID- 8536866
TI  - Cryoglobulinemia presenting after liver transplantation.
AB  - Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis
      C. Three patients undergoing transplantation for end-stage chronic hepatitis C in
      whom cryoglobulinemia with vasculitis developed after transplantation are
      described. Hepatitis C virus (HCV) infection was confirmed in the 3 patients by
      the presence of HCV RNA detected by polymerase chain reaction. The time interval
      between transplantation and the first expression of vasculitis was 1, 5, and 17
      months. Type II cryoglobulins were detected in the sera of all 3 patients. All
      patients developed cutaneous vasculitis, requiring digital amputation in 1 case.
      Two patients developed membranoproliferative glomerulonephritis. Plasmapheresis
      and the addition of cyclophosphamide led to an improvement in the renal disease
      in 1 case, whereas no treatment was able to reverse the renal failure in the
      other case. One patient developed an autoimmune hemolytic anemia 4 years after
      transplantation. One patient died of multiorgan failure 5 months after
      transplantation. We propose that HCV-associated cryoglobulinemia could become
      clinically significant only after orthotopic liver transplantation, possibly due
      in part to posttransplant increase in viremia as reflected by HCV RNA levels.
      These results confirm previous observations suggesting that HCV infection is
      important etiologically in the pathogenesis of cryoglobulinemia.

PMID- 8536867
TI  - The successful treatment of autoimmune hepatitis with 6-mercaptopurine after
      failure with azathioprine.
AB  - Although the treatment of choice for autoimmune hepatitis is glucocorticoids,
      their side effects make long-term use undesirable. Therefore, other
      immunosuppressive agents have been used to replace glucocorticoids in the long
      term treatment of autoimmune hepatitis, including azathioprine, a purine
      analogue. It is derived from 6-mercaptopurine, and these two drugs are often used
      interchangeably. However, these drugs have different toxicity profiles and may
      have clinically relevant differences in immunosuppressive activity in individual
      patients. We report 3 patients with autoimmune hepatitis who either could not
      tolerate or failed to improve on azathioprine but responded well to 6
      mercaptopurine.

PMID- 8536868
TI  - Therapeutics and inflammatory bowel disease: a guide to the interpretation of
      randomized controlled trials.
AB  - Randomized controlled trials are the optimal means of assessing the efficacy of
      new treatments. This report reviews the methodology of clinical trials in
      inflammatory bowel disease using examples from recent randomized trials of
      therapy for Crohn's disease and other gastrointestinal diseases to show key
      principles. Guidelines for the practicing clinician to evaluate these studies are
      provided.

PMID- 8536869
TI  - Detection of colorectal polyps by computed tomographic colography: feasibility of
      a novel technique.
AB  - BACKGROUND & AIMS: Computed tomographic colography (CTC) represents a novel
      technique for colorectal polyp detection. A prospective study was undertaken to
      determine the optimal CTC scanning parameters based on an artificial colon model
      and to assess the feasibility of CTC to detect clinically significant colorectal
      polyps. METHODS: A colon model was scanned by helical computed tomography at
      multiple parameters. Reformatted two-dimensional and three-dimensional images
      were then graded for polyp detection and image quality. Subsequently, 10 patients
      with known colon polyps underwent CTC immediately before colonoscopy. The number
      of polyps detected by two radiologists using CTC were compared with colonoscopy
      results that served as the gold standard. RESULTS: The optimal scanning
      parameters in the colon model were 5-mm collimation, 5 mm/s table speed, and 1-mm
      reconstruction interval. Ten patients had 30 polyps (range, 0.2-2.0 cm) by
      colonscopy, and all polyps > or = 0.5 cm were adenomas. Polyp detection by CTC
      for both observers was 100% (5 of 5) > or = 1 cm, 71% (5 of 7) between 0.5 and
      0.9 cm, and 11%-28% (2-5 of 18) < 0.5 cm. CONCLUSIONS: Based on this small,
      unblinded pilot study, CTC is feasible for colorectal polyp detection > or = 0.5
      cm in diameter.

PMID- 8536870
TI  - Interferon alfa therapy in patients with chronic hepatitis C and persistently
      normal aminotransferase activity.
AB  - BACKGROUND & AIMS: Chronic hepatitis C virus carriers may have repeatedly normal
      aminotransferase activity despite detectable viremia and histological hepatitis.
      The aim of this study was to determine the effect of interferon in this
      population. METHODS: Three million units of interferon alfa was administered 3
      times weekly for 6 months in 10 patients with chronic hepatitis C virus
      infection, repeatedly normal alanine aminotransferase activity, and chronic
      hepatitis on liver biopsy. Serum hepatitis C virus RNA was detected by polymerase
      chain reaction and quantified by branched DNA before, at the end, and 1 year
      after treatment. A liver biopsy was performed 1 year after treatment withdrawal.
      RESULTS: At treatment withdrawal, hepatitis C virus RNA levels had significantly
      decreased, but RNA was still detectable by polymerase chain reaction in 8 of 10
      patients. During the 1-year follow-up period, 6 of 9 patients had elevated
      aminotransferase activity on at least one occasion. One year after treatment
      withdrawal, RNA levels had returned to pretreatment values and no significant
      histological improvement was observed in the 7 patients who underwent liver
      biopsy. CONCLUSIONS: In patients with chronic hepatitis C and repeatedly normal
      aminotransferase activity, standard interferon therapy does not lead to sustained
      virological or histological responses despite a transient effect on hepatitis C
      virus replication.

PMID- 8536871
TI  - Investigating diarrhea in patients with acquired immunodeficiency syndrome.

PMID- 8536872
TI  - Maintenance therapy for Crohn's disease.

PMID- 8536873
TI  - Nicotine effects on prostaglandin-dependent gastric slow wave rhythmicity and
      antral motility in nonsmokers and smokers.
AB  - BACKGROUND & AIMS: Mechanisms of antral hypomotility with smoking are unknown.
      Slow wave disruption, which may be prostaglandin dependent, inhibits gastric
      motility. This study tested if nicotine reproduces motor effects of smoking and
      assessed the role of slow wave disruption in inducing hypomotility and the
      prostaglandin dependence of dysrhythmic responses. METHODS: Electrogastrography
      and antroduodenal manometry were performed in 9 nonsmokers and 9 smokers during
      transdermal nicotine treatment (14 mg). Studies were repeated after
      administration of 150 mg indomethacin daily for 3 days to test prostaglandin
      requirements of nicotine responses. RESULTS: Antral migrating motor complex
      periodicity and fasting and fed motility indices, not different in the groups
      under control conditions, decreased similarly in nonsmokers and smokers with
      nicotine. Tachygastria (> 4.5 cycle/min) increased from 2% +/- 2% to 16% +/- 3%
      of recording time, and arrhythmias (frequency instability index) increased from
      0.5 +/- 0.1 to 1.1 +/- 0.2 cycle/min with nicotine in nonsmokers (P < 0.05),
      which normalized with indomethacin. Electrogastrography results were unchanged in
      smokers. CONCLUSIONS: Nicotine evokes antral hypomotility in nonsmokers and
      smokers but evokes prostaglandin-dependent gastric dysrhythmias only in
      nonsmokers. Smokes show desensitization to nicotine-stimulated dysrhythmias.
      Thus, slow wave disruption is not essential to inhibit motor activity. This
      provides a model for the motor and myoelectric effects of smoking.

PMID- 8536874
TI  - Chronic unexplained diarrhea in human immunodeficiency virus infection:
      determination of the best diagnostic approach.
AB  - BACKGROUND & AIMS: Chronic unexplained diarrhea is a common complication of human
      immunodeficiency virus infection, although the best diagnostic approach is
      unknown. The purpose of our study was to evaluate the clinical use of endoscopy
      for the evaluation of this problem. METHODS: Patients infected with human
      immunodeficiency virus with chronic unexplained diarrhea underwent upper
      endoscopy to the jejunum followed by colonoscopy. RESULTS: Forty-eight patients
      were evaluated. A potential cause of diarrhea was found in 21 patients (44%; 95%
      confidence interval, 30%-58%). Colonoscopy with biopsy identified an etiology in
      13 patients, including cytomegalovirus colitis alone in 9. In all but 1 patient
      with colonic disease, the diagnosis was made by biopsy of the rectosigmoid colon.
      Upper endoscopy with biopsy identified microsporidiosis in 7 patients and
      cryptosporidiosis in 2 patients. Logistic regression analysis identified weight
      loss and duration of diarrhea (P < 0.001) as the only independent predictors for
      diagnosis. No patient without weight loss and a CD4 lymphocyte count of > 100/mm3
      had a diagnosis established. Of the 25 patients without a diagnosis in whom long
      term follow-up was available, improvement or spontaneous resolution of diarrhea
      occurred in 9 (38%). CONCLUSIONS: Clinical parameters are helpful in predicting
      which patients may benefit from endoscopic examination.

PMID- 8536875
TI  - Diagnosing dyspepsia: any controversies left?

PMID- 8536876
TI  - Genetic markers: the key to early diagnosis and improved survival in pancreatic
      cancer?

PMID- 8536877
TI  - ERCP meets C-K-ras: towards an improved diagnosis of pancreatic cancer.

PMID- 8536878
TI  - Interferoning with natural history: dollars and sense.

PMID- 8536879
TI  - Neural control of intestinal amino acid absorption.

PMID- 8536880
TI  - Granulomatous pancreatitis: Crohn's disease or sarcoidosis?

PMID- 8536881
TI  - Crohn's disease of the pancreas.

PMID- 8536882
TI  - Bad bile in the esophagus: gastroesophageal reflux or duodenogastric reflux?

PMID- 8536883
TI  - Hypercalcemic pancreatitis: from trypsinogen activation?

PMID- 8536884
TI  - Diagnostic tests to document Helicobacter pylori eradication.

PMID- 8536885
TI  - Bile salts and gallbladder mucin secretion.

PMID- 8536886
TI  - Microsatellite instability at multiple loci in gastric carcinoma:
      clinicopathologic implications and prognosis.
AB  - BACKGROUND & AIMS: Microsatellite instability (replication error [RER]-positive
      phenotype) is a frequent genetic alteration in gastric carcinomas. The clinical
      relationship between RER-positive and RER-negative gastric tumors is poorly
      characterized. The aim of this study was to investigate the relationship between
      the number of altered microsatellite loci and the clinicopathologic features of
      gastric carcinoma. METHODS: Five or 6 microsatellite loci were analyzed in 61
      gastric carcinomas using polymerase chain reaction. RESULTS: Twenty-one
      carcinomas (34.4%) had microsatellite instability: 7 at 1 locus, 2 at 2 loci, and
      12 at multiple loci. The comparison between the three groups (with none, 1 or 2,
      and more than 2 RER-positive loci) showed that RER-negative carcinomas and
      carcinomas with 1 or 2 RER-positive loci share features that differ from those of
      carcinomas with multiple RER-positive loci. The latter were all of the intestinal
      or atypical subtype and had lower DNA content, more prominent lymphoid
      infiltration, and less prevalent nodal metastases than carcinomas in the other
      two groups. The patients with carcinomas showing multiple RER-positive loci had a
      better prognosis. CONCLUSIONS: The finding of microsatellite instability in a
      single or few loci does not qualify a case as a mutator phenotype from a clinical
      standpoint. Gastric tumors with multiple RER-positive loci have a particular
      clinicopathologic profile leading to a better outcome.

PMID- 8536887
TI  - Oral budesonide as maintenance treatment for Crohn's disease: a placebo
      controlled, dose-ranging study. Canadian Inflammatory Bowel Disease Study Group.
AB  - BACKGROUND & AIMS: Budesonide is a corticosteroid with high topical anti
      inflammatory activity and low systemic activity due to rapid hepatic metabolism.
      The efficacy and safety of an oral controlled-release preparation of budesonide
      for maintenance of remission was evaluated in patients with ileal or ileocecal
      Crohn's disease. METHODS: In a double-blind, multicenter trial, 105 patients were
      randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily
      for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease
      Activity Index score of > 150 and a minimum increase of 60 points. RESULTS:
      Patients receiving 6 mg of budesonide had a median time to relapse or
      discontinuation of therapy of 178 days compared with 124 days in those receiving
      3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year,
      the rate of relapse in the group receiving 6 mg of budesonide was similar to the
      rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence
      of corticosteroid-associated effects were similar in the three groups.
      CONCLUSIONS: Oral controlled-release budesonide (6 mg/day) was well tolerated and
      prolonged remission in Crohn's disease of the ileum and proximal colon, but this
      effect was not sustained at 1-year follow-up.

PMID- 8536888
TI  - Common deleted region on the long arm of chromosome 5 in esophageal carcinoma.
AB  - BACKGROUND & AIMS: The existence of an unknown tumor-suppressor gene on 5q for
      esophageal carcinoma other than the APC gene has been suggested. The location of
      the putative tumor-suppressor gene on 5q, distinct from the APC gene, was
      examined. METHODS: Sixty-one primary esophageal carcinomas were examined for nine
      microsatellite loci by the polymerase chain reaction followed by polyacrylamide
      gel electorophoresis. Loss of heterozygosity at the APC gene locus also was
      examined by the polymerase chain reaction-restriction fragment length
      polymorphisms. RESULTS: Thirty-five of 61 esophageal carcinomas (57%) showed loss
      of heterozygosity at single or multiple loci on 5q, and the smallest common
      deleted region was identified at 5q31.1, the location of the IRF-1 gene locus.
      All tumors showing loss of heterozygosity at the APC gene locus showed complete
      or large interstitial deletions on 5q. CONCLUSIONS: Deletion at the APC gene
      locus may just be the result of large deletions on 5q and may not be important in
      esophageal carcinogenesis, and the IRF-1 gene or other gene(s) on 5q31.1 may be
      the true target of frequent deletions on 5q that may play an important role in
      the pathogenesis of the majority of esophageal carcinomas.

PMID- 8536889
TI  - Immunolocalization of alpha-integrin subunits and extracellular matrix components
      during human colonic organogenesis.
AB  - BACKGROUND & AIMS: The role of cell adhesion molecules in colonic organogenesis
      remains poorly understood. This study examined the expression of alpha-integrin
      subunits and extracellular matrix ligands during human colonic development.
      METHODS: Standard immunohistochemistry was used to characterize extracellular
      matrix and alpha-integrin subunit expression during development. RESULTS: At 9
      weeks, type-IV collagen and laminin were present underlying epithelium, around
      vascular structures, and surrounding inner circular muscle layer fibers.
      Fibronectin was uniformly expressed in the mesenchyme. Tenascin distribution was
      restricted to the presumptive muscle layer and, later, to the villus core and
      muscularis mucosae. The 9-week epithelium expressed alpha 2, alpha 3, alpha 5,
      and alpha 8, and, by 11 weeks, alpha 9. alpha 3, alpha 6, and alpha 8 expression
      was accentuated at the basal membrane. During transition from pseudostratified to
      simple columnar epithelium, a vertical alpha 2 gradient formed. Mesenchymal cells
      expressed alpha 5 and alpha 8 by 9 weeks. The developing muscularis (propria and
      mucosae) showed accentuated alpha 5 expression. By 16 weeks, alpha 8 expression
      localized to the muscularis mucosae and villus core. Mesenchymal vascular
      elements stained strongly with anti-alpha 2 and alpha 6 by 9 weeks. CONCLUSIONS:
      These observations show the complexity and overlap of adhesive receptor
      expression and ligands during development and reveal early cell commitment to the
      formation of specific structures.

PMID- 8536890
TI  - Initial endoscopy or empirical therapy with or without testing for Helicobacter
      pylori for dyspepsia: a decision analysis.
AB  - BACKGROUND & AIMS: Empirical therapy has been proposed for initial management of
      dyspepsia. The aim of this study was to evaluate initial endoscopy, empirical
      therapy, and testing for Helicobacter pylori in the management of patients with a
      new onset of dyspepsia. METHODS: Decision analysis was used to compare the direct
      medical charges in the first year after the onset of dyspepsia for patients
      managed by initial endoscopy or empirical therapy, with or without initial
      testing for H. pylori. RESULTS: Medical care charges were $2162.50 for initial
      endoscopy and $2122.60 for empirical therapy, a difference of 1.8%. For a 55-year
      old adult, life expectancy was 23.49 years for initial endoscopy compared with
      23.48 years for empirical therapy. Empirical therapy has lower charges than
      initial endoscopy when H2-receptor antagonists are used to prevent recurrence of
      dyspepsia. Initial noninvasive testing for H. pylori has lower charges than
      initial endoscopy if patients with dyspepsia with H. pylori receive antimicrobial
      therapy without endoscopy but would have higher charges if patients with H.
      pylori routinely have endoscopy. CONCLUSIONS: Surprisingly, the choice of optimal
      management strategy was a "toss-up." Only modest savings may result from practice
      guidelines that recommend empirical therapy in the management of patients with
      dyspepsia.

PMID- 8536891
TI  - Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous
      adenoma.
AB  - BACKGROUND & AIMS: Rectosigmoid villous adenomas (RVAs) account for approximately
      10% of all colorectal tumors. They have distinct pathological features, including
      abundant mucus secretion, possible malignant transformation, and multiple
      recurrences after conservative treatment. The aim of this study was to determine
      the nature of any changes in mucin gene expression in RVAs. METHODS: In situ
      hybridization was used to examine mucin messenger RNA expression in a series of
      22 patients with an RVA. Five normal rectal and colonic mucosae and five rectal
      adenocarcinomas were used as controls. RESULTS: In the 22 RVAs, we found an
      overexpression of MUC2 and an aberrant expression of MUC5AC. This MUC5AC
      expression was more intense in RVAs with low-grade dysplasia than in those cases
      with high-grade dysplasia. Moreover, in 4 cases, it was detected at a distance
      from the tumor in areas previously considered as normal by endoscopic and
      histological examination. CONCLUSIONS: MUC5AC seems to be a specific marker for
      RVAs and thus may be useful for the early detection of RVA recurrences after
      endoscopic laser treatment.

PMID- 8536892
TI  - Developmental regulation of transforming growth factor beta-mediated collagen
      synthesis in human intestinal muscle cells.
AB  - BACKGROUND & AIMS: The intestinal wall is formed by smooth muscle and the
      regulated deposition of specific collagen types. This study is the first to
      examine transforming growth factor beta (TGF-beta) in human fetal intestinal
      muscle. Studies localized TGF-beta within the muscularis propria, identified the
      cellular source, measured TGF-beta, and determined effects on collagen synthesis
      from 10 to 21 weeks of gestation. METHODS: Localization of TGF-beta within the
      intestinal wall and in cultured cells was determined immunohistochemically. TGF
      beta was measured by the CCL-64 cell growth inhibition assay. Collagen production
      was assayed as the uptake of 3H-proline into collagenase-digestible protein.
      Collagen types were identified by polyacrylamide slab gel electrophoresis and
      quantitated by densitometry. Experiments were performed in TGF-beta (50-200
      pg/mL) or anti-TGF-beta (50-200 micrograms/mL). RESULTS: TGF-beta 1 was localized
      in muscle cells of the muscularis propria and in culture. Muscle cells produced
      340% more TGF-beta at 11 weeks of gestation than at 20 weeks. At 10 weeks of
      gestation, TGF-beta inhibited collagen production by 38%, but stimulated collagen
      synthesis by 70% at 21 weeks of gestation. TGF-beta altered the expression of
      individual collagen chains in an age-specific manner. CONCLUSIONS: Smooth muscle
      cells secrete TGF-beta during human fetal intestinal development. TGF-beta
      stimulates or inhibits the expression of specific collagen chains depending on
      gestational age.

PMID- 8536893
TI  - Technical proficiency of trainees performing colonoscopy: a learning curve.
AB  - BACKGROUND AND PURPOSE: We sought to provide an objective measure of the
      technical progress of trainees learning colonoscopy. GI fellows in our training
      program perform colonoscopy under supervision throughout their 2 years of
      fellowship. METHOD: The frequency of fellows reaching the cecum in less than 30
      minutes was determined by one endoscopy instructor during the last 7 months of
      their first year of training and during the last 7 months of their second year.
      RESULTS: The mean success rate of reaching the cecum for seven first-year fellows
      was 54% (individual range, 25% to 86%). This compared with 86% for six second
      year fellows (individual range, 73% to 93%) and with 97% for the endoscopy
      instructor when he did procedures without a fellow. First-year fellows during the
      7-month "testing" periods believed they had reached the cecum in 5.7% of cases in
      which they had not. This was not a problem with second-year fellows. Counting
      colonoscopies done with all instructors in our program, fellows in this series
      each did an average of 149 colonoscopies during their first-year of training and
      328 by the end of their second. CONCLUSIONS: Increasing proficiency in reaching
      the cecum occurs with experience over time, and continues even after completion
      of formal training. Individual trainees also seem to learn colonoscopy at
      different rates. Depending on how one defines competency, it is possible that the
      minimum threshold number for technical competency in colonoscopy of 100
      procedures, as suggested by the ASGE, may be low.

PMID- 8536894
TI  - Endoscopic estimation of size: improved accuracy by directed teaching.
AB  - Previous studies have demonstrated the inaccuracy of endoscopic estimation of
      size. Although several devices have been developed to help improve estimation of
      size, none are convenient for clinical use. We have designed and evaluated a
      clinical teaching protocol to aid endoscopists in better estimating size.
      Thirteen "endoscopists" with varying levels of experience (none, less than 1
      year, more than 1 year) estimated the size of six steel ball bearings placed into
      a model colon and viewed with a videoendoscope. They were then taught to
      compensate for optic distortion and retested immediately after teaching and again
      1 month later. The mean error of estimation decreased from 28% before teaching to
      8% after teaching (p < .05) and rose to 12% 1 month later (p < .05). Although the
      indices of mean error decreased immediately after teaching in all groups, only
      those individuals with less than 1 year of endoscopic experience retained the
      improvement 1 month after teaching. We conclude that endoscopists can be taught
      how to compensate for the optic distortion encountered during endoscopy. This
      teaching is most effective if performed early in the training program.

PMID- 8536895
TI  - Biopsies of the ampullary region in patients suspected to have sphincter of Oddi
      dysfunction.
AB  - Tumors of the ampulla of Vater that develop within the ampulla can go
      unrecognized during endoscopic examination. Patients with intra-ampullary tumors
      may present with a clinical picture very similar to that of sphincter of Oddi
      dysfunction. We wished to determine what percentage of patients initially
      diagnosed with sphincter of Oddi dysfunction are later found to have an intra
      ampullary neoplasm. Sixty-nine consecutive patients were considered to have
      sphincter of Oddi dysfunction and subsequently were treated with endoscopic
      sphincterotomy. No gallstones were found in the gallbladder or bile duct.
      Patients returned for biopsies of the ampulla at least 10 days after the
      endoscopic sphincterotomy. Three patients (4.3%) were found to have ampullary
      adenocarcinoma. Thirty-six had normal results of biopsy analysis and 30 had
      inflammatory or fibrotic changes on biopsy specimens. No objective criteria
      (clinical, biologic, endoscopic, or radiographic) that would help to distinguish
      between an ampullary tumor and sphincter of Oddi dysfunction were identified.
      Biopsies of the ampulla should be performed in all patients suspected of having
      sphincter of Oddi dysfunction and treated by endoscopic sphincterotomy.

PMID- 8536896
TI  - Infusion of C1-inhibitor plasma concentrate prevents hyperamylasemia induced by
      endoscopic sphincterotomy.
AB  - Hyperamylasemia after endoscopic sphincterotomy is a common event, occurring in
      about 70% of cases. Clinical acute pancreatitis may also develop in 1% to 6% of
      cases. Previous attempts to prevent this reaction with inhibitors of exocrine
      pancreatic secretion (somatostatin and octreotide) provided conflicting and often
      disappointing results. Kallikrein is one of the proteases that sustain the
      inflammatory process in acute pancreatitis; the C1 inhibitor is the only
      physiologic inhibitor of the first component of the human complement cascade and
      is a major inactivator of kallikrein and Factor XII. Therefore, we tested the C1
      inhibitor in the prevention of hyperamylasemia in 40 consecutive patients
      undergoing endoscopic sphincterotomy for common bile duct stones or benign
      papillary stenosis. They were given either C1 inhibitor (20 cases) or placebo (20
      cases) before the procedure. Serum amylase levels were determined at baseline and
      2, 4, 8, and 24 hours thereafter. Significant differences in serum amylase levels
      between groups were observed at 2 hours (p < .01), 4 hours (p < .0005), and 8
      hours (p < .005) after sphincterotomy. The differences in amylase levels were
      also significant among the 24 subjects with pancreatic ductal filling (2 hours, p
      < .05; 4 hours, p < .005; 8 hours, p < .01) and the 9 patients with previous
      episodes of acute pancreatitis (4 hours, p < .05; 8 hours, p < .05; 24 hours, p <
      .05). The infusion of C1-inhibitor plasma concentrate resulted in a 50% increase
      in functional levels of C1 inhibitor (in the 8 cases for whom they were assayed),
      which persisted throughout the observation period.

PMID- 8536897
TI  - The role of pancreatic stenting in obstructive ductal disorders other than
      pancreas divisum.
AB  - Pancreatic ductal strictures may lead to pancreatitis, with associated pain and
      nausea. Very little literature is available regarding stent placement for this
      problem; the efficacy of stenting, expected stent viability, and safety of the
      procedure require further study. In this series, 21 patients with pancreatic
      ductal strictures underwent a total of 42 ERCPs with pancreatic stent placement.
      Eighty-six percent of patients experienced significant improvement in their
      symptom score after at least 1 session; however, relief was usually not evident
      until day 7. Stent viability averaged 26.9 days, but it was significantly longer
      for patients with pancreatic cancer. Overall, pancreatic ductal stenting can
      relieve symptoms of pain and nausea, but relief is usually short-lived. It may be
      useful only for short-term therapeutic trials and to provide temporary relief in
      highly selected cases.

PMID- 8536898
TI  - A comparison of nonionic versus ionic contrast media: results of a prospective,
      multicenter study. Midwest Pancreaticobiliary Study Group.
AB  - BACKGROUND: Pancreatitis is one of the most common complications associated with
      ERCP. Multiple factors have been implicated for this potentially serious
      complication. Numerous suggestions for minimizing risks at ERCP have been
      offered, one of which is to use nonionic, low osmolarity contrast agents for
      pancreatic injection. Results of previous studies comparing different contrast
      media have been inconclusive. METHODS: To evaluate the role contrast material
      plays in the development of post-ERCP pancreatitis, the Midwest
      Pancreaticobiliary Group performed a prospective double-blind controlled study. A
      total of 1,979 consecutive ERCP patients were enrolled, and 1,659 patients with
      pancreatic duct injections were divided into subgroups according to the
      complexity of the ERCP. Post-ERCP pancreatitis was compared between similar
      groups. Patients were randomized to receive injections of nonionic, low
      osmolarity contrast or standard ionic contrast media. RESULTS: The overall
      incidence of post-procedural pancreatitis was 10.2%. Those with diagnostic ERCP
      had the lowest incidence at 5.6%. Therapeutic procedures (12.3%) and sphincter of
      Oddi manometry (15.2%) had higher rates. Those injected with standard (ionic)
      contrast had an incidence of 10.4% and after injection with lower osmolar
      (nonionic) contrast, there was a 10% post-procedural pancreatitis rate.
      CONCLUSIONS: Patients with more complex procedures develop pancreatitis more
      frequently. The use of low osmolar (nonionic) contrast media does not decrease
      the incidence of post-ERCP pancreatitis.

PMID- 8536899
TI  - Diagnostic utility of K-ras mutational analysis on bile obtained by endoscopic
      retrograde cholangiopancreatography.
AB  - BACKGROUND: Because K-ras oncogene mutations are present in more than 90% of
      pancreaticobiliary tumors, we tested prospectively whether K-ras mutational
      analysis of bile samples obtained during ERCP was superior to conventional bile
      cytology for diagnosis of malignancy. METHODS: Bile samples from 20 patients
      undergoing ERCP for evaluation of jaundice were examined by both cytologic study
      and the polymerase chain reaction for the presence of K-ras oncogene mutations.
      RESULTS: Polymerase chain reaction products were amplified from the bile of 8 of
      12 patients with malignancy and 3 of 8 with benign disease; K-ras oncogene
      mutations were present in 4 of 8 polymerase chain reaction products from
      malignant samples but absent in all 3 from benign samples. No cytologic results
      were positive for malignancy. CONCLUSIONS: Bile obtained during ERCP can yield
      positive results in K-ras mutational analysis, even when results of conventional
      bile cytology are negative. In this study, K-ras mutational analysis had a
      sensitivity of 33% (4 of 12), a specificity of 100%, and a positive predictive
      value of 100% for diagnosis of malignancy.

PMID- 8536900
TI  - A prospective, double-blind trial of somatostatin analog (octreotide) versus
      glucagon for the inhibition of small intestinal motility during endoscopic
      retrograde cholangiopancreatography.
AB  - BACKGROUND: Glucagon is effective when used as an antimotility agent during ERCP,
      but at high doses it may cause nausea and vomiting. Octreotide acetate, a long
      acting synthetic analog of somatostatin, inhibits contractility of the small
      intestine and is generally well tolerated. The purpose of this study was to
      determine if octreotide given prior to ERCP reduced the requirement for glucagon
      and enhanced patient tolerance for the procedure. METHODS: Patients undergoing
      ERCP (n = 100) performed for a variety of indications (but not sphincter of Oddi
      manometry) were randomly assigned to receive normal saline solution or octreotide
      at a total dose of 25 micrograms, 50 micrograms, or 100 micrograms diluted in
      normal saline solution prior to the procedure. Glucagon was subsequently
      administered (as needed, to inhibit intestinal motility) by endoscopists who were
      blinded to the test substance given prior to the procedure. RESULTS: For all
      treatment groups, the dose of glucagon required to inhibit intestinal motility in
      patients who received octreotide prior to the procedure was not significantly
      different from the dose administered to patients who received normal saline
      solution. There was no significant difference in the incidence of nausea and
      vomiting when individual test groups were compared to the control group.
      CONCLUSION: Nausea and vomiting after ERCP were uncommon in all treatment groups.
      Administration of octreotide prior to ERCP did not significantly reduce the dose
      of glucagon required to inhibit intestinal motility. Tolerance for ERCP was
      similar for patients given octreotide when compared with those given glucagon to
      inhibit small intestinal motility.

PMID- 8536901
TI  - Consistent improvement in sphincterotome orientation with manual grooming.
AB  - BACKGROUND: During ampullary cannulation with standard sphincterotomes, wire
      orientation is frequently to the right of 0 and can not always be rotated to the
      12 o'clock ideal. It is not known if the presence of a wire guide alters a
      sphincterotome's orientation or if grooming in a standardized manner improves the
      orientation in the majority of cases. METHODS: The intra-ampullary range of
      orientation of a double channel sphincterotome was prospectively evaluated before
      and after catheter grooming in 25 patients undergoing ERCP. The range of
      orientation was also measured with and without an indwelling biliary wire guide
      in 14 cases. RESULTS: The maximal right orientation of the untrained
      sphincterotomes was 35 +/- 16 degrees; with a wire guide it was 33 +/- 22
      degrees. Maximal left orientation was 17 +/- 16 degrees, wire guided it remained
      19 +/- 14 degrees. Manual grooming shifted the mean maximal left orientation of
      the sphincterotomes to -37 +/- 28 degrees (p < 0.0001), permitting 80% of groomed
      sphincterotomes to achieve a 0 (12 o'clock) orientation and 100% to orient 10
      degrees or less from zero. CONCLUSIONS: The presence of the wire guide did not
      alter the orientation of the sphincterotome. Because manual grooming reliably
      improved the orientation of double-channel sphincterotomes, it should be
      routinely performed before their use.

PMID- 8536902
TI  - Predictive factors for early mortality after percutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a safe access procedure
      for enteral nutrition. The purpose of this investigation is to identify
      predictive factors for early mortality after PEG. METHODS: A retrospective review
      of the hospital records of 416 patients undergoing PEG from June 1, 1989, through
      December 31, 1991, was conducted. Patient demographics, admitting diagnosis,
      indication for PEG, risk factors for early mortality, and cause and date of death
      were reviewed. Logistic regression analysis was used to develop a model to
      predict early mortality after PEG. The follow-up period ranged from 1 to 30
      months. RESULTS: The overall mortality rate in this review was 227 of 416
      patients (54.6%). The 7- and 30-day case fatality rates were 39 of 416 (9.4%) and
      97 of 416 (23.3%), respectively. Logistic regression analysis showed that urinary
      tract infection (odds ratio (OR) = 3.05; 95% confidence interval (CI) = 1.45
      6.43) and previous aspiration (OR = 6.86; 95% CI = 3.27-14.4) were predictive
      factors for death at 1 week after PEG. Patients who had both risk factors had a
      48.4% probability of dying within 7 days after PEG insertion, whereas those who
      had no risk factors had a 4.3% probability of death. Urinary tract infection (OR
      = 2.00; 95% CI = 1.17-3.41), previous aspiration (OR = 3.62; 95% CI = 2.00-6.55),
      and age greater than 75 years (OR = 2.49; 95% CI = 1.47-4.21) were predictive
      factors for death at 1 month after PEG. Patients who had all three risk factors
      had a 67.1% probability of death at 1 month while those who had no risk factors
      had a 10% probability of death. CONCLUSIONS: A subgroup of patients exists that
      has a very high mortality rate after PEG. Less invasive ways of nutritionally
      supporting these high-risk patients should be evaluated.

PMID- 8536904
TI  - Endoscopic Nd:YAG treatment of superficial gastric carcinoma: experience in 18
      Western inoperable patients.
AB  - Endoscopic treatment of superficial gastric cancer has been reported to be
      effective by many Japanese teams. In this study, the Nd:YAG laser was used to
      treat superficial gastric carcinoma in inoperable Caucasian patients with the aim
      of obtaining a complete response, i.e., disappearance of the lesion
      endoscopically and biopsy specimens negative for cancer. Eighteen patients
      unsuitable for surgery with various endoscopic patterns of superficial gastric
      cancer were treated with the Nd:YAG laser. The endoscopic pattern was type I in 4
      patients, type II in 10 (5 type IIa, 1 type IIb, 2 type IIc, 2 mixed IIa + IIc),
      and type III in 4. Staging by echoendoscopy was performed in 11 patients (T1N0).
      Nd:YAG laser destruction of the gastric tumor was performed in all cases, with a
      mean of 4.4 laser sessions per patient. Tumor response was assessed by endoscopy
      and biopsy. Follow-up averaged 33 +/- 23 (SD) months. Five patients died of
      diseases unrelated to gastric cancer. An initial complete response was obtained
      in 16 (89%) patients after a mean of 1.7 laser sessions; histologic evidence of
      cancer persisted in 2 patients during the entire follow-up period. Among patients
      with an initial complete response, recurrence was observed in 2. One of them was
      successfully re-treated. At the end of the follow-up period, 14 (77.7%) of the 18
      patients had a complete tumoral response; only 4 patients had histologic evidence
      of cancer. In 3 of these 4 patients, pretherapeutic echoendoscopic staging had
      not been performed. Among the 14 patients exhibiting a complete response, 3 had
      negative biopsy results more than 5 years after diagnosis. No complications
      occurred. In gastric cancer classified as T1N0 on the basis of pretherapeutic
      echoendoscopy, a high tumor response rate and even 5-year disease-free survival
      can be obtained with endoscopic Nd:YAG laser treatment. Endoscopic laser
      destruction thus appears to be a valuable therapeutic alternative to surgery in
      inoperable patients with superficial gastric cancer.

PMID- 8536903
TI  - Gastroscopic findings in Mediterranean Kaposi's sarcoma (non-AIDS).
AB  - The frequency and degree of gastrointestinal involvement in patients with
      Mediterranean Kaposi's sarcoma (non-AIDS), a newly recognized form of Kaposi's
      sarcoma, is unknown. Eighty-seven patients with Mediterranean Kaposi's sarcoma
      proven by skin and/or nodal biopsy underwent endoscopic study of the upper
      gastrointestinal tract. Of these, 71 (81.6%) had gastrointestinal lesions. All
      these patients had lesions in the stomach. Additional lesions were detected in
      the esophagus in 19 patients and in the proximal duodenum in 8 patients, whereas
      additional lesions in both the esophagus and duodenum were identified in 2
      patients. The lesions were classified into 4 types according to their size,
      shape, and color. Most types of lesions showed characteristic discoloration, but
      lesions with the appearance and color of normal mucosa that histologically were
      shown to be Kaposi's sarcoma were also identified. The high prevalence of
      gastrointestinal involvement in patients with Mediterranean Kaposi's sarcoma (non
      AIDS) suggests that an endoscopic examination of the upper gastrointestinal tract
      may be useful in non-AIDS-related forms of Kaposi's sarcoma.

PMID- 8536905
TI  - Does routine intravenous glucagon administration facilitate colonoscopy? A
      randomized trial.
AB  - BACKGROUND: Previous studies on the routine use of glucagon in colonoscopy have
      produced conflicting results. METHODS: Two separate studies were performed. In
      one study (Study 1), 80 consecutive patients were randomized after cecal
      intubation to receive 1 mg glucagon (n = 41) or placebo (n = 39), intravenously,
      in double-blind fashion. In a second study (Study 2) 90 sedated patients
      undergoing colonoscopy were randomized to receive 1 mg glucagon (n = 46) or
      placebo (n = 44), intravenously, just before colonoscope insertion. In each
      study, colonoscope insertion and withdrawal time, therapeutic intervention time,
      the presence and severity of colonic spasm, colonoscopy yield, and side effects
      were recorded. RESULTS: Mean withdrawal time in Study 1 was similar in those
      receiving glucagon (6.85 min) and in those receiving placebo (6.92 min). Mean
      insertion time in Study 2 (5.07 min) was identical between groups. Spasm scores
      and colonoscopy yield did not differ between glucagon and placebo in either
      study. There was a trend toward more side effects (nausea and vomiting) with
      glucagon in Study 1. Glucagon did not facilitate insertion or withdrawal in the
      subset of patients with diverticulosis. CONCLUSIONS: Routine use of intravenous
      glucagon in a dosage of 1 mg does not facilitate colonoscopy by experienced
      examiners.

PMID- 8536906
TI  - Videoendoscopic anoscopy: a new technique for examining the anal canal.

PMID- 8536907
TI  - Ischemia-induced tissue remodeling: magnetic enteral gastrostomy in a porcine
      model.

PMID- 8536908
TI  - Simultaneous combination of endoscopic sclerotherapy and endoscopic ligation for
      esophageal varices.

PMID- 8536909
TI  - A technique to examine the underlying mucosa in patients with AIDS and severe
      Candida esophagitis.

PMID- 8536910
TI  - Tandem wire mesh stents for palliation of obstructing gastroduodenal
      adenocarcinoma.

PMID- 8536911
TI  - Nutcracker esophagus: severe muscular hypertrophy on endosonography.

PMID- 8536912
TI  - Endoscopic laser Zenker's diverticulotomy.

PMID- 8536913
TI  - How long does it take to learn endoscopy?

PMID- 8536914
TI  - ERCP for all?

PMID- 8536915
TI  - Role of fluoroscopy in Maloney dilation of esophageal strictures.

PMID- 8536916
TI  - Color vision and endoscopic diagnosis.

PMID- 8536917
TI  - Complicated common duct stones treated with extracorporeal shockwave lithotripsy.

PMID- 8536918
TI  - J-tube knot in the stomach.

PMID- 8536919
TI  - Fine-needle aspiration cytology guided by endoscopic ultrasonography. Results in
      141 patients.

PMID- 8536920
TI  - Prospective audit of upper gastrointestinal endoscopy in two regions of England:
      safety, staffing, and sedation methods.

PMID- 8536921
TI  - Changes in proto-oncogene activity in the testis of the frog, Rana esculenta,
      during the annual reproductive cycle.
AB  - Proto-oncogenes are said to influence the regulation of cellular growth and
      differentiation. Myc, Fos, Jun, and Mos protein localization has been studied by
      immunocytochemistry in the testis of the frog, Rana esculenta, during the annual
      reproductive cycle. Oncoproteins have been localized in the primary and secondary
      (I and II) spermatogonia (SPG). Myc and Mos also appear in I and II spermatocytes
      (SPC) while Jun appears in II SPC. Myc, Fos, and Jun in SPG translocate in the
      nucleus during the periods of active spermatogenesis. Myc, Fos, and Jun are also
      localized in Sertoli cells. Fos is present in interstitial cells during the
      period characterized by the androgen peak which precedes the sharp increase of
      estradiol. It is suggested that proto-oncogene activity exerts a regulatory role
      in steroidogenesis and spermatogenesis.

PMID- 8536922
TI  - The appearance of proopiomelanocortin early in vertebrate evolution: cloning and
      sequencing of POMC from a Lamprey pituitary cDNA library.
AB  - A proopiomelanocortin (POMC)-like hormone has been cloned and sequenced from a
      pituitary cDNA library of upstream migrant (prespawning) sea lamprey, Petromyzon
      marinus. The clone, designated LPP-1, consisted of 986 nucleotides, with an open
      reading frame of 277 amino acids, including a signal peptide of 22 amino acids.
      Like POMCs from more recently evolved vertebrates, lamprey POMC contained domains
      which corresponded to alpha-MSH, ACTH, and beta-endorphin. However, sequences
      corresponding to gamma- and beta-MSH are absent or likely nonfunctional,
      respectively, in this cDNA. Northern blot analyses showed low but detectable
      expression levels of LPP-1 in larvae and strong expression in parasitic adults
      and prespawning animals. These observations indicate that a recognizable POMC,
      distinct from proenkephalin, has an ancient lineage within subphylum Vertebrata,
      likely dating back to the last common ancestor of the lamprey and gnathostome
      lines.

PMID- 8536923
TI  - Effects of presence of an egg and calcium deposition in the shell gland on levels
      of messenger ribonucleic acid of CaBP-D28K and of vitamin D3 receptor in the
      shell gland of the laying hen.
AB  - Levels of calbindin-D28K (CaBP-D28K) mRNA and vitamin D3, 1 alpha, 25(OH)2D3,
      receptor (VDR) mRNA in the intestine and shell gland were measured in the laying
      hen during the ovulatory cycle by Northern and slot blot analyses. In addition,
      effects of presence of an egg and calcium deposition in the shell gland on the
      levels of both mRNAs were studied either by delay in oviposition (retaining the
      egg in the shell gland beyond the expected time of oviposition) or premature
      oviposition (emptying the shell gland and arrest of calcium deposition). During
      the ovulatory cycle mRNA levels of CaBP-D28K and of VDR remained relatively
      constant in the intestine. In contrast, both mRNA levels of the shell gland were
      low when there was an egg in the infundibulum, magnum, and isthmus, but
      significantly increased when there was an egg in the shell gland during shell
      formation. The im injection of indomethacin 3 hr before expected ovulation
      delayed oviposition but increased neither shell thickness nor mRNA levels of CaBP
      D28K and of VDR. On the other hand, premature oviposition reduced mRNA levels of
      both CaBP-D28K and VDR in the shell gland. These results suggest that the
      presence of an egg and calcium deposition in the shell gland may be a stimulatory
      factor for synthesis and accumulation of CaBP-D28K mRNA and VDR mRNA in
      association with calcification.

PMID- 8536924
TI  - Gonadotrophin-regulated production of immunoactive inhibin and androgen by
      cultured testicular cells from chicken embryos.
AB  - To study the potential intragonadal role of inhibin and inhibin-related proteins
      in the developing gonad, a method was developed to culture testicular cells of
      chicken embryos. A single-step collagenase/DNase digestion was used to disperse
      the cells. Except for the primordial germ cells and the erythrocytes, the cells
      attached well to plastic culture dishes. Moreover, they could easily be grown in
      the absence of serum or other additives. Inhibin secretion was measured using a
      heterologous radioimmunoassay validated for use in this species. The fetal
      testicular cells secreted high amounts of immunoactive inhibin and remained
      responsive to gonadotrophins. Two different cell populations could be recognized
      in monolayers of testicular cells: the first population had a fibroblast-like
      stromal appearance, resembling interstitial cells; the second had an epitheloid
      appearance and contained large numbers of refractile vacuoles, resembling Sertoli
      cells. Both cell populations were enriched using a Percoll density gradient. The
      epitheloid cells displayed a higher capacity to secrete immunoactive inhibin,
      while the stromal cells were responsible for the bulk of androgen secretion. FSH,
      but also LH, stimulated inhibin secretion in the epitheloid cells. Although ovine
      LH was the most potent stimulus for androgen secretion by the stromal cells,
      ovine FSH was also capable of increasing androgen output in stromal cells and to
      a lesser extent in epitheloid cells. As the two enriched cell populations were
      still contaminated by other cell types, this may indicate, as in other species,
      that FSH-induced paracrine factors are involved in the regulation of androgen
      secretion in the developing gonad.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536925
TI  - Hormonal regulation of skin gland development in the toad (Bufo boreas): the role
      of the thyroid hormones and corticosterone.
AB  - At metamorphic climax, anurans develop skin glands that migrate from the
      epidermis into the dermis. Thyroxine (T4) stimulates skin gland differentiation
      and migration, and a previous study showed that corticosterone (Cort) treatment
      of larvae is inhibitory. The current study used histological analyses to address
      the mechanism of Cort's prevention of skin gland development. Two types of glands
      were observed in controls at metamorphic climax: The first type resembled
      granular glands found in adults and the second resembled mucous glands.
      Differential staining revealed that the two gland morphologies represented
      functionally distinct granular and mucous glands. Treatment of larvae from Gosner
      Stages 35-42 with Cort or the goitrogen, thiourea (Thio), caused a reduction in
      the number of mucous (P < 0.05) but not granular glands. The similarity in the
      effects of Cort and Thio suggested that Cort inhibited skin gland development
      indirectly by down-regulating the hypothalamo-pituitary-thyroid axis. T4
      treatment of larvae reversed the effects of Thio (T4+ Thio-treated animals);
      however, animals treated with T4+ Cort had no skin glands of either type.
      Triiodothyronine (T3) treatment of larvae resulted in the complete absence of
      skin glands with a limited number of gland nests (epidermal precursors of dermal
      skin glands), but stimulated epidermal growth. T3+ Thio- or T3+ Cort-treated
      animals also completely lacked skin glands. These data suggest that T3 favors
      epidermal growth at the cost of skin gland differentiation. Furthermore, we
      suggest that Cort inhibits skin gland development indirectly through its
      enhancement of T4 to T3 conversions, and that inhibition of skin glands is caused
      by an increase in T3 resulting from Cort treatment.

PMID- 8536926
TI  - Stimulation of osmoregulating processes in the perfused gill of the crab
      Pachygrapsus marmoratus (Crustacea, Decapoda) by a sinus gland peptide.
AB  - Isolated posterior gills of the hyper-hyporegulating crab Pachygrapsus marmoratus
      were perfused with extracts of homologous sinus glands. Sinus gland extracts
      stimulated the influx of Na+ ions and increased the transepithelial potential
      difference in the gills in a dose-dependent and reversible fashion. The
      bioactivity of extracts prepared from crabs that had been acclimated to 10/1000
      salinity for at least 1 week was not significantly different from that of
      extracts prepared from seawater (36/1000 salinity) crabs. The perfusion
      experiments with both extracts containing two sinus glands significantly
      increased Na+ influx by about 150% and transepithelial potential difference by
      about 45%. Sinus gland extracts also increased the Na+/K(+)-ATPase activity by
      54% in incubated posterior gills. The bioactivity of extracts was reduced by
      pronase and trypsin, but not by heating for 10 min at 100 degrees. The molecular
      weight of the responsible factor(s) was > 5000 Da. Thus, the sinus gland of P.
      marmoratus is concluded to be involved in the neuroendocrine control of
      osmoregulation and to contain a peptide(s) that directly influences brachial
      function.

PMID- 8536927
TI  - Glucagon of caviomorphs and other tetrapods immunohistochemically investigated
      with two antisera against the N- and C-terminal portions of the molecule.
AB  - Pancreatic sections from diverse tetrapods, including various species of
      caviomorph rodents, were immunohistochemically investigated using two antisera
      which reacted with the N- and C-terminal portions of the glucagon molecule. While
      the antiserum against the N-terminal portion stained alpha cells in all the
      species studied, the antiserum against the C-portion failed to stain alpha cells
      in two caviomorphs of the Caviidae family (guinea pig and cuis) and in one of the
      Octodontidae family (degu). The observations in guinea pig and degu were
      expected, since their glucagons differ from those of many other tetrapods in the
      C-terminal portion of the molecule. In this paper, the cuis was added to these
      two species. It is noteworthy that among the caviomorphs studied herein (nine
      species), immunohistochemical differences were detected only in the three above
      mentioned species and did not involve higher taxa, thus suggesting that these
      modifications are relatively recent in the evolution of this group of rodents.

PMID- 8536928
TI  - Plasma prolactin and luteinizing hormone during termination and onset of
      photorefractoriness in intact and pinealectomized European starlings (Sturnus
      vulgaris).
AB  - Plasma levels of prolactin and luteinizing hormone have been examined in intact
      and pinealectomized European starling (Sturnus vulgaris) during termination and
      onset of photorefractoriness. Photorefractory starlings exposed to long (18L:6D)
      daily photoperiods for 10 weeks were pinealectomized. One week after pinealectomy
      these birds, along with the intact and sham-operated birds, were transferred to
      short (8L:16D) daily photoperiods. After 10 weeks on short day lengths the daily
      photoperiod was switched to long (18L:6D) and the birds remained on this regime
      for a further 10 weeks. Plasma prolactin and luteinizing hormone were determined
      prior to pinealectomy and then weekly throughout the experiment. Molt scores were
      also recorded. Profiles of both the hormones and the molt pattern were similar in
      pinealectomized, sham-operated, and intact control starlings. In European
      starlings the pineal gland does not seem to exert significant effects on the
      photoinduced rise in plasma prolactin and luteinizing hormone seen in
      photosensitive birds. It is also suggested that pinealectomy has no significant
      effect on the dissipation and onset of photorefractoriness assessed from plasma
      luteinizing hormone secretion in this bird.

PMID- 8536929
TI  - Involvement of estradiol in a catecholamine inhibitory tone of gonadotropin
      release in the rainbow trout (Oncorhynchus mykiss).
AB  - The present study aimed to examine the inhibitory action of catecholaminergic
      neurons on the release of gonadotropin II (GtH2) in female rainbow trout at
      different stages of the reproductive cycle. Estradiol (E2) implants in sexually
      immature female increased blood E2 levels (from 0.55 to about 9 ng/ml) and
      pituitary GtH2 contents (from 15 to about 8500 ng/pit), but did not modify blood
      GtH2 levels or pituitary dopamine (DA) and norepinephrine contents. Subsequent
      treatment by alpha-methyl-p-tyrosine (MPT) increased blood GtH2 levels (from 0.5
      to about 3 ng/ml) and decreased pituitary DA levels, only in E2-implanted fish.
      MPT also increased blood GtH2 levels of sexually recrudescent (about threefold)
      and sexually mature (about twofold) fish. In the periovulatory period, there was
      a highly significant positive correlation between blood E2 levels--which fall up
      until ovulation--and ability of MPT to increase GtH2 release. GtH2 release in
      rainbow trout is concluded to be inhibited by a brain-pituitary DA tone and there
      are relationships between this inhibitory tone and the level of estradiol.

PMID- 8536930
TI  - cDNA cloning of thyroid hormone receptor beta for the Japanese flounder.
AB  - cDNA encoding the beta type of thyroid hormone receptor (THR) was cloned from a
      lambda gt10 library prepared from the whole bodies of metamorphosing flounder
      (Paralichthys olivaceus). The deduced amino acid sequence of the flounder THR
      beta (fTHR beta 1) showed higher homologies to the known THR beta s of other
      vertebrate animals than to THR alpha s, including flounder THR alpha s. Unlike
      any other THR, fTHR beta 1 possessed an insertion sequence composed of nine amino
      acids in the region prior to the hormone-binding domain. PCR analyses suggested
      the presence of transcripts for another THR beta (fTHR beta 2) that had a longer
      insertion sequence than fTHR beta 1. The analyses further suggested that the cDNA
      sequences of the two flounder THR beta s most likely shared a constant sequence
      except for a 60-base additional sequence found only in fTHR beta 2. The flounder
      genome possessed a single gene for both fTHR beta 1 and beta 2, suggesting that
      the two THR beta variants are produced from the same gene through an alternative
      splicing system.

PMID- 8536931
TI  - Identification of sex in hatchling loggerhead turtles (Caretta caretta) by
      analysis of steroid concentrations in chorioallantoic/amniotic fluid.
AB  - A major difficulty in sea turtle conservation is the inability to nonlethally and
      noninvasively identify the sex of hatching sea turtles. Traditional sexing
      techniques such as plasma sex steroid quantification cannot be applied to
      hatchlings without sacrificing the hatchlings or utilizing invasive procedure.
      This paper presents a technique for sexing hatchling sea turtles by analysis of
      sex steroid concentrations in egg chorioallantoic/amniotic fluid (CAF).
      Metabolites of estradiol-17 beta (E) and testosterone (T) in CAF are best
      expressed as an index or E:T ratio. Chorioallantoic/amniotic fluid E:T ratios for
      males (0.5 +/- 0.1) were significantly lower than those for females (2.2 +/-
      0.3). When separated by utilizing an E:T ratio of 1.25 as the determinant index
      value, 27 of 28 hatchlings were designated correctly as males (E:T < 1.25) or
      females (E:T > or = 1.25). Sex was verified for all hatchlings by gonadal
      histology. This study shows significant concentrations of T and E metabolites in
      CAF and plasma of hatchling loggerhead turtles and illustrates the use of a
      nonlethal, noninvasive method for determining sex, which could be potentially
      utilized for other endangered reptile and avian species.

PMID- 8536932
TI  - Effects of insulin, glucagon, and somatostatin on the release of somatostatin-25
      and somatostatin-14 from rainbow trout, Oncorhynchus mykiss, pancreatic islets in
      vitro.
AB  - Somatostatins are a diverse family of peptides known to modulate insulin and
      glucagon secretion as well as to stimulate glycogenolysis and lipolysis in
      salmonid fish. In this study, Brockmann bodies (bisected to yield hemi-islets)
      isolated from rainbow trout, Oncorhynchus mykiss, were used to study the effects
      of insulin, glucagon, and somatostatin at various concentrations of glucose (1,
      5, and 10 mM) on pancreatic somatostatin release. The release of somatostatin-25,
      the most predominate form of somatostatin in salmonid pancreas, was stimulated by
      insulin in the presence of 1 and 5 mM glucose but not in the presence of 10 mM
      glucose, whereas glucagon stimulated somatostatin-25 release only in the presence
      of high (10 mM) glucose. Somatostatin-25 release also was stimulated by
      somatostatin-14. The secretion of somatostatin-14 was suppressed by insulin in
      the presence of 5 and 10 mM glucose and was stimulated by glucagon in the
      presence of high (10 mM) glucose. These results indicate that insulin, glucagon,
      and somatostatin-14 are regulators of somatostatin-14 and somatostatin-25
      pancreatic release in rainbow trout and that these effects are modulated by
      glucose.

PMID- 8536933
TI  - Isolation and characterization of insulin-like growth factor-I from rainbow
      trout, Oncorhynchus mykiss.
AB  - Insulin-like growth factor-I (IGF-I) has been purified from plasma of adult
      rainbow trout, Oncorhynchus mykiss. Plasma samples were collected 48 hr following
      injection of recombinant tuna growth hormone at a dose of 0.5 microgram/g body
      weight. Acid-ethanol extract of plasma was fractionated by gel filtration on a
      Sephadex G-50 superfine column. Two-step ion-exchange chromatography on DEAE-52
      and then Mono-S columns followed. Rainbow trout IGF-I was further purified by
      immunoaffinity chromatography with anti-recombinant coho salmon IGF-I (rsIGF-I)
      serum and HPLC on a reverse-phase C18 column. During purification, trout IGF-I
      was monitored by SDS-PAGE, immunoblotting with anti-IGF-I-serum, homologous
      radioimmunoassay (RIA) for salmon IGF-I, and sulfation bioassay. The trout IGF-I
      appeared on SDS-PAGE as a single band with a molecular weight of 7 kDa, the same
      size as rsIGF-I. The partial N-terminal amino acid sequence (residues 1-20) was
      identical to the predicted mature trout IGF-I cDNA sequence. Trout IGF-I cross
      reacted with anti-rsIGF-I serum in immunoblotting and its dilution curve was
      parallel to the rsIGF-I standard curve in salmon RIA. In concentrations of 50 and
      500 ng/ml, trout IGF-I significantly stimulated sulfation uptake by the cultured
      branchial cartilage of rainbow trout. This stimulatory effect of trout IGF-I was
      dose-dependent and similar in its biological potency to rsIGF-I.

PMID- 8536934
TI  - Control of secretory lipid droplets in the harderian gland by testosterone and
      the photoperiod: comparison of two species of hamsters.
AB  - Harderian glands of mammals secrete lipid. They are markedly sexually dimorphic
      in Syrian (golden) hamsters (Mesocricetus auratus): female glands consist almost
      entirely of one cell type (type I) with small lipid droplets, whereas glands of
      males have both type I and type II cells, with large lipid droplets. Siberian
      (Djungarian) hamsters (Phodopus sungorus) have sexually monomorphic Harderian
      glands, with both type I and type II cells. We used a morphometric technique to
      quantify the proportions of small (type 1) and large (type 2) lipid droplets in
      these two species, in relation to the presence or absence of testosterone and to
      variations in the photoperiod. In Syrian hamsters, orchidectomy led to a marked
      increase in the proportion of type 1 lipid droplets in males kept in long (but
      not short) day photoperiods. In contrast, treatment of females with testosterone
      led to an increase in type 2 lipid droplets. Short-day photoperiods in both sexes
      led to an increase in the proportion of type 2 lipid droplets and this was
      prevented by pinealectomy. In Siberian hamsters, on the other hand, castration or
      short photoperiods had no effect on Harderian gland morphology in either sex.
      These results suggest that some property of type 2 lipid droplets is important to
      Syrian hamsters during the autumn and winter. Syrian hamsters have a dimorphic
      Harderian gland and testosterone maintains the basic sexual dimorphism during the
      long days of spring and summer; a pineal-mediated mechanism, perhaps the drop in
      serum prolactin levels, leads to an increase in type 2 lipid droplets with the
      short days of autumn and winter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536935
TI  - In vitro secretion of insulin-like growth factor-binding proteins from liver of
      striped bass, Morone saxatilis.
AB  - In vitro secretion of insulin-like growth factor-binding proteins (IGFBPs) from
      liver of striped bass (sb: Morone saxatilis) was studied using a simple organ
      culture system. Liver cubes (1 mm3) were cultured in minimum essential medium
      with Earle's salts containing 0.1% bovine serum albumin and 100 U/ml penicillin
      in 5% CO2/95% O2 at 16 degrees. The amount of double-stranded DNA in these
      cultured liver cubes did not change by 192 hr in the culture, but decreased by
      216 hr. Four IGFBPs (a 23- to 24-kDa protein, a 28- to 30-kDa protein, a 35- to
      39-kDa protein, and an 85- to 90-kDa protein) were identified in striped bass
      serum by Western ligand blotting; two of these IGFBPs, 23-24 kDa (sbIGFBP-1) and
      28-30 kDa (sbIGFBP-2), were consistently detected in culture media by Western
      ligand blot analysis. The intensity of the blot for sbIGFBP-2 was consistently
      greater than that of sbIGFBP-1, which was no longer secreted after 96 hr in
      culture. The effects of hormones and growth factors on IGFBP secretion by liver
      tissue were measured after 48 hr in culture. sbIGFBP-1 in the medium was
      significantly decreased by adding ovine prolactin (10 micrograms/ml), bovine
      insulin (100 micrograms/ml), and bovine IGF-I (100 ng/ml), but was increased by
      17 beta-estradiol (E2: 5 and 50 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536936
TI  - Evidence that the inhibitory effects of stress on reproduction in teleost fish
      are not mediated by the action of cortisol on ovarian steroidogenesis.
AB  - Ovarian follicles of goldfish, common carp, and the sparid Pagrus auratus (New
      Zealand snapper) were incubated in vitro to assess the effects of cortisol (F) on
      ovarian steroidogenesis. Unstimulated goldfish follicles produced little
      testosterone (T) or 17 beta-estradiol (E2), whereas both carp and snapper
      follicles spontaneously produced E2 and to a lesser extent T. Goldfish follicles
      produced increased amounts of E2 in response to treatment with human chorionic
      gonadotropin (hCG), whereas carp and snapper follicles did not. However,
      stimulation of carp follicles with maturational carp gonadotropin (cGTH-II)
      resulted in dose-dependent increases in production of E2. Treatment of follicles
      of all three species with T resulted in E2 production to levels as high as or
      higher than those following treatment with hCG or cGtH-II. Cotreatment of
      follicles with T and hCG or cGTH-II did not result in higher E2 production than
      treatment with T alone. Goldfish follicles treated with 25-hydroxycholesterol
      showed increases in E2 production that were similar to those occurring following
      treatment with T. Treatment of follicles with F at a range of doses up to 1
      microgram.ml-1 had no inhibitory effect on T or E2 production in any treatment
      combination in any of the species examined. In several cases, follicles incubated
      with T and/or hCG produced more E2 in the presence of F than they did without F.
      The results suggest either that the observed inhibitory effects of stress in a
      range of teleost species are not mediated by F or that they arise higher in the
      endocrine pathway than at the level of ovarian steroidogenesis.

PMID- 8536937
TI  - Insulin binding and internalization in hagfish red blood cells.
AB  - Binding of porcine 125I-insulin (0.15 nM) to hagfish red blood cells was time
      dependent, reaching equilibrium after 1 hr at 10 degrees. The specific 125I
      insulin binding to hagfish red blood cells was reversible, and unlabeled insulin
      accelerated the dissociation of 125I-insulin bound to receptors from a T1/2 of 60
      min in cells suspended in medium alone to 23 min in medium containing 8 microM
      nonradioactive insulin. Porcine insulin and desoctapeptide insulin competed for
      specific binding of 125I-insulin in a dose-dependent manner, whereas glucagon and
      somatostatin did not. For porcine insulin, Scatchard analysis produced a
      curvilinear plot, suggesting multiple affinity binding sites with high-affinity
      and low-affinity association constants (Ka) 0.2 x 10(9) M-1 and 0.27 x 10(7) M-1,
      respectively. A total of 2090 binding sites per hagfish red blood cell was
      calculated. Sixty-two percent of the bound 125I-insulin was found to be
      internalized into the hagfish red blood cells. Less degradation of 125I-insulin
      was observed by Sephadex G-50 chromatography compared to human red blood cells.

PMID- 8536938
TI  - Pineal gland and melatonin affect testicular status in the adult marsh rice rat
      (Oryzomys palustris).
AB  - The effects of the presence or absence of the pineal gland and of melatonin
      administration were examined on testicular maintenance, regression, and
      recrudescence in adult male rice rats. Pinealectomy at the beginning of the study
      caused significant testicular regression in animals housed on both long (16L:8D)
      and short (12L:12D) photoperiods (Experiment 1). Sham-operated males maintained
      testicular weight on 16L:8D and underwent testicular regression on 12L:12D. The
      magnitude of testicular regression in pinealectomized animals was reduced
      relative to that of sham-operated animals housed on a short photoperiod and
      occurred on a different time course. Animals pinealectomized after testicular
      regression had occurred on 12L:12D demonstrated delayed photostimulated
      testicular recrudescence when housed on 16L:8D, while spontaneous testicular
      recrudescence was unaffected in animals maintained on 12L:12D (Experiment 2).
      Administration of melatonin via subcutaneous implants at the beginning of the
      study (Experiment 3) produced similar effects on testicular function attributed
      to pinealectomy in Experiment 1. Finally, melatonin implants administered after
      the testes regressed on 12L:12D delayed both photostimulated and spontaneous
      testicular recrudescence in animals housed on long or short photoperiods,
      respectively (Experiment 4). These results suggest a role for both the pineal
      gland and melatonin at various stages of the annual reproductive cycle of the
      male rice rat.

PMID- 8536939
TI  - Red drum somatolactin: development of a homologous radioimmunoassay and plasma
      levels after exposure to stressors or various backgrounds.
AB  - A specific radioimmunoassay (RIA) for measurement of red drum (Sciaenops
      ocellatus) somatolactin (rdSL) was developed using somatolactin purified from red
      drum pituitaries and antisera to rdSL raised in rabbits. The rdSL antisera
      specifically bound to cells in the pars intermedia bordering the neurohypophysis
      in red drum and Atlantic croaker (Micropogonias undulatus) pituitaries. These
      cells correspond to the periodic acid-Schiff-positive cells and are distinct from
      the lead-hematoxylin-positive cells which include the alpha-melanocyte
      stimulating hormone (alpha-MSH) cells. No cross-reaction in the rdSL RIA was
      observed with red drum growth hormone (GH), prolactin (PRL), recombinant tuna GH,
      Atlantic croaker maturational GTH (GTH II), human GH, PRL, human follicle
      stimulating hormone alpha subunit (FSH alpha), bovine FSH beta subunit, human
      adrenocorticotropic hormone, synthetic mammalian alpha-MSH, beta-MSH, gamma-MSH,
      delta-MSH, or cortisol. Dilution curves of plasma and pituitary extracts from red
      drum and Atlantic croaker were parallel to the rdSL standard curve. The assay had
      a sensitivity of 0.14 ng/ml plasma when 100 microliters plasma was assayed. SL
      levels in juvenile red drum ranged from 0.5 to greater than 32 ng/ml in plasma
      and from 0.5 to 13.5 micrograms/mg tissue in pituitaries. No significant
      elevation in plasma SL levels was observed in either red drum or Atlantic croaker
      exposed to acute stressors. In contrast, plasma SL levels were significantly
      higher in both red drum and Atlantic croaker exposed to dark backgrounds than in
      those exposed to light backgrounds. These results provide the first evidence that
      SL may play a role in adaptation to dark backgrounds in sciaenid fishes.

PMID- 8536940
TI  - Protein kinase-C mediates chicken vasoactive intestinal peptide stimulated
      prolactin secretion and gene expression in turkey primary pituitary cells.
AB  - This set of experiments investigated the role of protein kinase-C (PKC) as a
      second messenger in vasoactive intestinal peptide (VIP)-stimulated prolactin
      (PRL) secretion and PRL mRNA abundance. Dispersed anterior pituitary cells (5 x
      10(5) or 10(6) cells/tube) were isolated from laying turkeys and incubated in 1.0
      ml of M-199. In Experiment 1, 10(-7) M VIP increased PRL secretion three- to
      fivefold. Prolactin mRNA abundance was higher in VIP-treated cells (11.45 +/-
      2.11 arbitrary optical unit; AOU) than control cells (4.59 +/- 1.2 AOU). In
      Experiment 2, the addition of 10(-12), 10(-10), 10(-8), and 10(-6) M phorbol 12
      myristate 13-acetate (PMA; PKC agonist) increased PRL release from 8.5 +/- 0.7 to
      14.9 +/- 1.1, 17.2 +/- 1.3, 18.1 +/- 2.2, and 18.7 +/- 2.8 micrograms/10(6)
      cells, respectively. PRL mRNA abundance was significantly (P < 0.01) increased in
      only 10(-6) M PMA treatment. In Experiment 3, PKC desensitization decreased VIP
      stimulated PRL release from 10.0 +/- 2.3 to 4.2 +/- 0.6 micrograms/5 x 10(5)
      cells and PMA-induced release from 7.1 +/- 1.3 to 2.7 +/- 0.3 micrograms/5 x
      10(5) cells. VIP and PMA up-regulated PRL mRNA abundance was decreased two- to
      fourfold by PKC desensitization. In Experiment 4, 10(-6) M staurosporine (ST; PKC
      antagonist) decreased both 10(-7) M VIP-stimulated PRL secretion from 7.86 +/-
      2.9 to 2.43 +/- 0.5 micrograms/5 x 10(5) cells and 10(-8) M PMA-stimulated PRL
      secretion from 4.26 +/- 0.2 to 2.23 +/- 0.3 micrograms/5 x 10(5) cells (P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536942
TI  - Immunocytochemical localization of IGF-I in the ovary of the red seabream, Pagrus
      major.
AB  - There are many biochemical and molecular biological data indicating that IGF-I is
      present in teleost fish. The present study examines red seabream for the presence
      and cellular distribution of IGF-I in the ovarian follicles during oocyte growth
      and final maturation of oocytes by immunocytochemistry. Immunoreactivity appeared
      in the granulosa cells at the lipid stage. Immunoreactivity became strong at the
      primary yolk globule stage and diminished in intensity during development of
      maturational competence (responsiveness to maturation-inducing steroid) and final
      maturation of oocytes. Intense immunoreactivity was also localized in the outer
      layer of the zona radiata and the peripheral region of the ooplasm at the primary
      yolk globule stage. Postovulatory follicles had low immunoreactivity in the early
      phase of degeneration. These immunocytochemical observations show that the
      granulosa cell layer is the main site of IGF-I production. IGF-I may be involved
      in granulosa cell proliferation and differentiation.

PMID- 8536941
TI  - Somatostatin-, vasoactive intestinal peptide-, and granulin-like peptides
      isolated from intestinal extracts of goldfish, Carassius auratus.
AB  - Three new peptides were originally isolated from intestinal extracts of goldfish.
      They were structurally related with somatostatin, vasoactive intestinal peptide
      (VIP), and granulin (GRN) and thus termed goldfish somatostatin (gSS-28), gVIP,
      and gGRN, respectively. The primary structures of these peptides were determined
      as: SVESSNHLPA 10RERKAGCKNF20YWKGFTSC for the gSS-28;
      HSDAVFTDNY10SRYRKQMAAK20KYLNSVLA-NH2 for the gVIP, and VIHCDSSTIC10
      PDGTTCCLSP20YGVWYCCPFS30MGQCCRDGIH40CCRHGYHCDS50TSTHCLR for the gGRN. The amino
      acid sequence of the gSS-28 was more similar (79-86% similarity) to somatostatins
      obtained in anglerfish, flounder, and sculpin, but far (21% similarity) from the
      catfish somatostatin, whereas goldfish and catfish belong to the same superorder.
      The structure of the gVIP was closely related to that of the cod VIP; only one
      residue (Tyr13) being substituted for Phe13 in the cod VIP. Comparing amino acid
      sequences of VIPs obtained in various vertebrates, the primary structure of this
      peptide was revealed to be relatively well conserved among vertebrates. In
      addition, the dose-response curve for the effect of gVIP on the short-circuit
      current (Isc) across the eel intestine was similar to that of human VIP,
      suggesting that VIPs in vertebrates have similar effect. The amino acid sequence
      of gGRN was 96% identical to that of carp GRN-1; only two residues (Ser6-Ser7)
      being substituted for Ala6-Ala7 in the carp GRN-1. The physiological significance
      of these peptides is discussed.

PMID- 8536943
TI  - Making males from females: the effects of aromatase inhibitors on a
      parthenogenetic species of whiptail lizard.
AB  - The parthenogenetic whiptail lizard Cnemidophorus uniparens provides a good model
      for the study of sex determination and sexual differentiation because genetic
      variation is minimal and all unmanipulated embryos will develop as females. Thus
      any deviation from the established course of development can be identified as a
      treatment effect. Previous work has shown that early prenatal treatment with
      CGS16949A, a nonsteroidal aromatase inhibitor, causes hatchlings to develop as
      males. The present study explores more fully the effects of dosage and timing of
      application of CGS16949A and examines the sex-reversing potential of CGS20267, a
      new and reputedly more potent aromatase inhibitor. Eggs were treated with a range
      of dosages of the aromatase inhibitors. Hatchlings that received 1 microgram or
      more of either inhibitor were all male, while those that received 0.1 microgram
      or less were all female. No difference in potency between the two compounds was
      detected. Animals treated with 100 micrograms of CGS16949A on Day 20 of
      incubation or later were all female, while those treated on Day 5 were all male.
      Seven sex-reversed male parthenogens have been raised to sexual maturity. The
      animals appear similar morphologically and behaviorally to males of the sexually
      reproducing whiptail species. Spermatogenesis and spermiogenesis have been
      confirmed by histological examination of the testes and by postcopulatory cloacal
      swabs. Application of aromatase inhibitors has been shown to sex-reverse both
      avian and reptilian species. In mammals, the male-determining gene of the Y
      chromosome (SRY) may code for an intrinsic aromatase inhibitor. Studies show the
      gene's product has a binding domain which recognizes regulatory elements in the
      promoter of the aromatase gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536944
TI  - Urotensin II from the river lamprey (Lampetra fluviatilis), the sea lamprey
      (Petromyzon marinus), and the paddlefish (Polyodon spathula).
AB  - Urotensin II was isolated from extracts of the whole brain of the river lamprey
      (Lampetra fluviatilis) and the sea lamprey (Petromyzon marinus). The primary
      structure of the peptide from both species is the same (Asn-Asn-Phe-Ser-Asp-Cys
      Phe-Trp-Lys-Tyr-Cys-Val) and this amino acid sequence is identical to that of
      urotensin II from the dogfish and skate. Consistent with previous morphological
      studies indicating that the Agnatha lack a caudal neurosecretory system,
      urotensin II was not detected in an extract of P. marinus spinal cord. The data
      suggest that the urotensin II may have functioned in the earliest vertebrates as
      a neurotransmitter/neuromodulator in the central nervous system rather than as a
      neurohormone of the caudal neurosecretory system. Urotensin II was also isolated
      from an extract of the spinal cord of a chondrostean fish, the paddlefish
      (Polyodon spathula). The primary structure of the paddlefish urotensin II (Gly
      Ser-Thr-Ser-Glu-Cys-Phe-Trp-Lys-Tyr-Cys-Val) is the same as that of another
      chondrostean, the sturgeon (Acipenser ruthenus). The study provides further
      evidence for a widespread distribution of urotensin II in vertebrate species and
      suggests that the primary structure of the peptide is better conserved in these
      phylogenetically ancient fish than in teleosts.

PMID- 8536945
TI  - A peptide from the caudal neurosecretory system of the dogfish Scyliorhinus
      canicula that is structurally related to urotensin I.
AB  - Using reversed-phase HPLC in combination with a radioimmunoassay for ovine
      corticotropin-releasing hormone (CRH), a peptide with CRH-like immunoreactivity
      was isolated in pure form from an extract of the caudal spinal cord region of the
      spotted dogfish, Scyliorhinus canicula. The primary structure of the peptide was
      established as Pro-Ala-Glu-Thr-Pro-Asn-Ser-Leu10-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-
      Glu-Met-Ile- Glu20-Ile-Ala-Lys-His-Glu-Asn-Gln-Gln-Met-Gln30-Ala-Asp-Ser- Asn-Arg
      Arg-Ile-Met - Asp-Thr40-Ile.NH2. This amino acid sequence shows moderate
      structural similarity to Catostomus urotensin I (51%) and to human CRH (56%). The
      data provide, therefore, chemical evidence to support the conclusions of earlier
      immunohistochemical studies that the diffuse caudal neurosecretory system of
      elasmobranchs produces a peptide that is immunochemically related to teleost
      urotensin I peptides. However, the primary structure of urotensin I has been
      poorly conserved during evolution.

PMID- 8536946
TI  - Some properties of the ecdysteroid receptor in the salivary gland of the ixodid
      tick, Amblyomma hebraeum.
AB  - Salivary gland degeneration in ixodid ticks is triggered by an ecdysteroid
      hormone. We used [3H]ponasterone A (PoA) as a specific ligand to detect the
      ecdysteroid receptor in the salivary glands of large, partially fed female ticks
      (Amblyomma hebraeum Koch; Acari: Ixodidae). Binding of [3H]PoA was thermolabile
      and sensitive to pronase, but not to DNase or RNase, indicating that the ligand
      binds to a protein. Scatchard analysis of [3H]PoA binding strongly suggested the
      presence of an ecdysteroid receptor in cytosolic and nuclear extracts of the
      tissue. The Kd and Bmax for PoA binding in cytosol were 0.72 +/- 0.09 nM and 175
      +/- 12 fmol/mg protein, respectively (n = 8). Corresponding figures for nuclear
      extract were 1.1 +/- 0.5 nM and 282 +/- 35 fmol/mg protein, respectively (n = 3;
      P > 0.05 compared to cytosol). The relative ability of unlabeled ecdysteroids to
      compete for [3H]PoA binding was (in descending order): PoA > muristerone A >
      makisterone A > 20-hydroxyecdysone > mesylinokosterone > ecdysone. The Kd
      estimated for 20-hydroxyecdysone (probably the natural hormone) correlates very
      well with its physiological potency in inducing salivary gland degeneration in
      vivo and in organ culture. None of the vertebrate steroids tested (estradiol,
      testosterone, progesterone, and corticosterone) was able to displace PoA binding
      at a concentration 10(5) times higher than PoA. The cytosolic form of the
      receptor migrated to the 3.2 S region of a 10-40% sucrose density gradient.

PMID- 8536947
TI  - Changes in brain GnRH associated with photorefractoriness in house sparrows
      (Passer domesticus).
AB  - Temperate zone birds terminate reproduction when they become photorefractory. In
      many species, refractoriness is "absolute" in that gonadal regression occurs
      before day length declines, and individuals are reproductively unresponsive even
      to continuous light. Based on studies of a few species, this form of
      refractoriness appears to be associated with a reduction (compared with breeding
      and/or photosensitive birds) in numbers of hypothalamic cells and fibers that are
      immunoreactive for gonadotropin releasing hormone (GnRH). Some species display
      "relative" refractoriness, in that day length must decline before gonadal
      regression occurs, and individuals never lose the capacity to respond to very
      long days. A few reports suggest that GnRH levels in the brain do not change in
      relatively refractory birds. House sparrows (Passer domesticus) regress their
      gonads sooner when day length declines during summer than they do if photoperiod
      is not permitted to decline after the summer solstice (i.e., they appear to be
      "relatively" refractory). However, if held on long days they eventually regress
      the gonads despite no decline in photoperiod (they appear to be "absolutely"
      refractory). In this experiment, we tested whether gonadal regression was
      associated with changes in hypothalamic GnRH in adult male house sparrows. We
      used immunocytochemistry (primary antibody sensitive to both forms of avian GnRH)
      to compare the distribution and number of GnRH-immunoreactive cells and fibers
      among reproductively active individuals on long days, "absolutely" refractory
      individuals on long days, and presumably "relatively" refractory individuals
      induced to regress by shortened days. Similar reductions in ir-GnRH cell number
      and cell size occurred in both groups of refractory birds compared with birds
      still in breeding condition. Gonadal regression also was correlated with reduced
      staining intensity of cell bodies and reduced fiber staining, but these
      reductions were somewhat more pronounced in the "absolutely" than the
      "relatively" refractory birds. We discuss these results in light of other studies
      of avian GnRH changes with reproductive stage. Our results are consistent with
      the idea that house sparrows become absolutely refractory, regardless of whether
      exposed to a decline in photoperiod. However, the results also suggest that
      relative refractoriness may induce gonadal regression through a cessation of GnRH
      secretion, whereas absolute refractoriness involves down-regulation of peptide
      production as well.

PMID- 8536948
TI  - Atrial natriuretic peptide stimulates aldosterone production by turkey (Meleagris
      gallopavo) adrenal steroidogenic cells.
AB  - The inhibitory action of atrial natriuretic peptides (ANPs) on mammalian
      aldosterone synthesis is well documented. In addition, other work indicates that
      ANP and an analogue of its second messenger, 8-Br-cGMP, inhibit aldosterone
      production by chicken adrenal steroidogenic cells. However, the interaction
      between angiotensin II (AII) and ANP in the regulation of avian aldosterone
      production is poorly understood because chicken adrenal steroidogenic cells, the
      commonly used in vitro avian model, are comparatively unresponsive to AII. By
      contrast, turkey (Meleagris gallopavo) adrenal steroidogenic cells are sensitive
      to AII. Thus, in the present study, the action of ANPs and related peptides and
      their interaction with other stimulators of aldosterone production were
      investigated using freshly isolated and briefly cultured turkey adrenal
      steroidogenic cells. Surprisingly, several ANPs [rat (r), human (h), chicken
      (c)], and rat brain natriuretic peptide (rBNP) were as efficacious as [Ile5]AII
      for stimulating aldosterone production (2 hr) in freshly isolated cell
      suspensions but were less potent than [Ile5]AII (ED50 of ANPs approximately 5-10
      nM; [Ile5]AII ED50 approximately 0.1 nM). In addition, chicken ANP enhanced
      maximal aldosterone production induced by [Ile5]AII (1 nM), K+ (25 mM), and hACTH
      (1-39) (ACTH) (1 nM): maximal enhancement of the action of these secretagogues
      was +49%, +137% and +15%, respectively (P < 0.05; n = 3). Furthermore, other ANPs
      and related peptides [rBNP and bovine aldosterone secretion inhibiting factor
      (bASIF)] enhanced maximal [Ile5]AII-induced aldosterone production: the order of
      maximal enhancement was rBNP (+180%) > hANP/rANP (+50%) > bASIF (+25%) (P < 0.05;
      n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8536949
TI  - Calcium-dependent signal transduction by the hypertrehalosemic hormone in the
      cockroach fat body.
AB  - The hypertrehalosemic hormones (HrTH) are insect peptides that stimulate the fat
      body to synthesize trehalose. The present research investigated the relative
      importance of extra- and intracellular Ca2+ for HrTH signal transduction in the
      fat body of the cockroach, Blaberus discoidalis. Although trehalose synthesis
      could be stimulated significantly by B. discoidalis HrTH (Bld-HrTH) in the
      absence of Ca2+, the presence of Ca2+ was necessary to attain a maximum hormonal
      response. Entry of extracellular Ca2+ mediated by ionophores (A23187, ionomycin)
      produced no significant hypertrehalosemic effects, whereas release of
      intracellular Ca2+ by thimerosal or thapsigargin significantly stimulated
      trehalose synthesis. The hypertrehalosemic effect by thimerosal occurred
      independently of extracellular Ca2+. Dantrolene inhibits intracellular Ca2+
      release, and its presence partially suppressed Bld-HrTH-dependent
      hypertrehalosemia. In conclusion, the presence of either extracellular Ca2+ or
      intracellular Ca2+ enhanced the Bld-HrTH response, but agents that affected
      intracellular Ca2+ release produced the more conclusive effects.

PMID- 8536950
TI  - In vitro effects of ACTH on interrenal corticosteroidogenesis during early larval
      development in rainbow trout.
AB  - Interrenal tissue from embryonic and larval rainbow trout (Oncorhynchus mykiss)
      was cultured in vitro and exposed to various doses of adrenocorticotropin (ACTH)
      to document the ontogeny of interrenal responsiveness to tropic stimulation.
      Resting and acute stress-induced changes in whole-body cortisol levels in vivo
      were also measured to determine if the corticosteroid stress response first
      develops with the onset of interrenal responsiveness to ACTH. No evidence was
      found that the hypothalamic-pituitary-interrenal (HPI) axis of rainbow trout is
      transiently activated prior to hatching. In vivo, a corticosteroid stress
      response was first observed 2 weeks after hatching, and stress-induced cortisol
      levels (at 1 hr poststress) were significantly higher 3 weeks after hatching than
      they were at 2 or 4 weeks after hatching. In contrast, cultured interrenal tissue
      produced significant levels of cortisol in response to ACTH at the time of
      hatching, and in vitro cortisol production by the interrenal increased
      significantly between 3 and 4 weeks after hatching. Interrenal sensitivity to
      ACTH did not change appreciably with development. We conclude that (1) the final
      maturation of the corticosteroid stress response in rainbow trout occurs at the
      level of the brain and/or sensory inputs and not at the level of the interrenal
      cell; (2) negative feedback mechanisms within the HPI axis develop 3 to 4 weeks
      after hatching; and (3) the period between 3 and 4 weeks after hatching may be
      homologous to the stress hyporesponsive period after birth in mammals and thus
      could be a stage when environmental influences can permanently alter the
      development of the corticosteroid stress response in rainbow trout.

PMID- 8536951
TI  - Using loss of heterozygosity data in affected pedigree member linkage tests.
AB  - Linkage analysis can be used to test the hypothesis that a marker locus of known
      location segregates independently from a presumed disease gene. One way to test
      this hypothesis is to measure the similarity of marker alleles among pairs of
      relatives affected with the disease. When the disease under consideration is
      cancer, it is possible to take advantage of the marker alleles in tumors to
      revise the similarity measure obtained from the observations made in
      constitutional tissue. Only cancers that arise through the model of recessive
      oncogenesis are amenable to this revised analysis. This model postulates that
      cancer is caused by somatic genetic changes which result in the loss of one or
      both copies of a normal allele at a tumor suppressor locus. If an individual's
      inherited genotype is heterozygous at the marker locus, the model of recessive
      oncogenesis suggests that we may observe loss of constitutional heterozygosity at
      the marker locus in the tumor. In this report, we how how to incorporate this
      loss of heterozygosity data into affected pedigree member linkage tests. The
      revised procedure is illustrated using data obtained from relatives with breast
      cancer. Substantial improvement in the power to reject the different chromosome
      hypothesis is obtained when loss of heterozygosity is observed in multiple
      relatives with the same marker alleles retained in the tumors.

PMID- 8536952
TI  - Simulation study comparing interval estimates for the recombination fraction.
AB  - Three interval estimation procedures were evaluated to determine the method which
      provides the most accurate estimates for the recombination fraction, 0. The lod
      0.83 support interval, the jackknife confidence interval, and the confidence
      interval based on estimated asymptotic standard error were compared by
      calculating the coverage probabilities of each. Family data that were simulated
      under the model of a single fully penetrant, dominant disease locus at some
      distance, 0, from fully informative matings were used. Comparisons were based on
      1,000 random samples of size 20,60, and 100 families. In addition, a methodology
      for obtaining prediction intervals for 0 was developed. This procedure is of
      practical use and does not require asymptotic assumptions based on large sample
      theory. The results provide an a priori idea about precision of the estimates, as
      well as empirical interval estimates of 0. Graphs of the authors' Monte Carlo
      intervals are presented for these simulations. Investigators studying different
      traits, however, could condition specifically on the family structure and
      distribution of the disease they are investigating and obtain similar graphs.

PMID- 8536953
TI  - Evaluating a new algorithm for linking maternal and newborn medical records.
AB  - Linking material and newborn medical records is a valuable tool for assessing the
      relationship between maternal variables and fetal outcome. This study evaluated
      the Center for Disease Control's newly developed maternal and newborn medical
      record linkage system, a computer program that uses weighted variables to
      determine the most likely maternal and newborn pairs. Any newborn record not
      achieving a set minimum score with a maternal record remains nonmatched. The
      objectives of the study were to estimate the program's matching accuracy,
      determine causes of incorrect matches and nonmatches, develop suggestions for
      program revisions, and evaluate the effects of the revisions. The study sample
      included 521 matched and 247 nonmatched maternal and newborn medical records from
      seven Ohio hospitals. Of all available newborn records (10,068), 574 (5.7%) did
      not match with maternal records; for those in which a match occurred, the authors
      ascertained a 98% matching accuracy and determined explanations for nonmatched
      and incorrectly matched records. The authors noted a greater prevalence of birth
      defects and prematurity among newborns with nonmatched records than among those
      with matched records. Program revisions, therefore, focused on reducing the
      prevalence of nonmatched records. The revised program reduced the prevalence of
      nonmatched records from 5.7% to 3% but reduced matching accuracy.

PMID- 8536954
TI  - No association of apolipoprotein A-IV codon 347 and 360 variation with
      atherosclerosis and lipid transport in a sample of mixed hyperlipidemics.
AB  - Genetic variation at the apolipoprotein (apo) A-I/C-III/A-IV gene cluster on
      chromosome 11 has been associated with differences in occurrence of
      atherosclerosis and with variability in lipid levels among hypercholesterolemic
      hypertriglyceridemic individuals. The functional cause of the association is not
      known, but polymorphisms of the apo A-IV gene are of interest because apo A-IV is
      involved in both triglyceride and cholesterol metabolism. Two mutations in the
      apo A-IV gene, 347T->S and 360Q->H, are known to cause amino acid substitutions
      in the mature protein. These polymorphisms were typed in a sample of 119 subjects
      with high cholesterol and high triglycerides in whom carotid artery wall
      thickness was previously shown to be strongly associated with silent polymorphic
      variation in the A-I/C-III/A-IV gene cluster. The relative allele frequencies
      were 0.83 and 0.17 for codon 347T->, and 0.95 and 0.05 for codon 360Q-> H. These
      polymorphisms did not show a statistically significant relationship with
      prevalent hypertension, diabetes, or cardiovascular disease or with plasma lipid
      levels. Most importantly, these amino acids substitutions in apo A-IV were not
      associated with carotid artery wall thickness. Therefore, the genetic cause of
      disease variability in a sample of mixed hyperlipidemics is not amino acid
      substitutions in codons 347 or 360 of the apoliproteins A-IV gene.

PMID- 8536955
TI  - Polymorphism at VNTR locus 3 to the apolipoprotein B gene in a Tunisian
      population: difference from other ethnic groups.
AB  - The Hypervariable region (HVR) detected at the 3' end of the apolipoprotein B
      (Apo B) locus has been the subject of numerous studies. As for many VNTR
      (variable number of tandem repeat), this locus is highly polymorphic and until
      now about 20 alleles have been described. The genotype distribution in all
      populations follows the Hardy-Weinberg predictions. A bimodal pattern of allele
      frequency distribution is apparent in all Caucasoid populations. We have analyzed
      the frequencies of different alleles in a Tunisian population (123 individuals)
      by the polymerase chain reaction technique and compared our results to those
      obtained in several ethnic groups. It appears that the distributions of the
      allele frequencies are very different: for Caucasoid populations, there are two
      peaks of frequencies for alleles with 36 and 48 repeats, but alleles of
      intermediate lengths are more frequent. Hixson et al. [(1993) Hum Genet 91:475
      479] have shown a similar difference between black and white American
      populations. We found the same results in a black African group. Some of the
      repeat units of this HVR contain a Ssp I restriction site and digestion of the
      PCR products by this enzyme gives different patterns on gradient acrylamide gel
      [Desmarais et al., 1993, Nucleic Acids Res 21:2179-2184.] The DNA of African
      individuals (42) has been analyzed to discover the origin of this new allele.
      Preliminary results indicate that these particular alleles probably arose by
      introgression from the African population into the Tunisian one.

PMID- 8536956
TI  - Angiotensin-converting enzyme genotypes in the high- and low-risk area for
      coronary heart disease in Finland.
AB  - The deletion/deletion genotype of the insertion (I)/deletion (D) polymorphism of
      the angiotensin-converting enzyme (ACE) gene has been suggested to be a risk
      factor for myocardial infarction (MI). The objective of this study was to
      evaluate whether genotype distributions of the I/D polymorphism of the ACE gene
      are different between individuals from high-risk and low-risk areas for coronary
      heart disease in the genetically isolated population of Finland and to assess the
      impact of this genetic risk factor by comparing individuals with different
      parental histories of MI. Representative population-based samples of middle-aged
      men (n = 363) and women (n = 358) from two areas of Finland were used. The area
      had a borderline significant effect on the prevalence of the genotype DD (beta =
      0.35, SE = 0.16, X2 = 470, df = 1, P = 0.03), the DD genotype being more
      prevalent in eastern Finland (the high-risk area). The II genotype was more
      prevalent in women with parental history of MI, so we could not replicate the
      previous findings of the risk-increasing effect of DD genotype in this sample.
      Although the observed difference in the ACE DD genotype between the high-risk and
      low-risk areas for coronary heart disease might represent one of the genetic
      factors contributing to the difference in risk of coronary heart disease between
      eastern and southwestern Finland, the data emphasize the fact that also other
      risk factors, including other genes, contribute to this difference and the high
      incidence of MI in Finland.

PMID- 8536957
TI  - Segregation analysis of breast cancer in a population-based sample of
      postmenopausal probands: The Iowa Women's Health Study.
AB  - Inheritance of a major susceptibility gene for breast cancer has been primarily
      investigated in families with early-onset disease. However, familial clustering
      of late-onset breast cancer is well documented, and genetic factors may also be
      relevant. In the Iowa Women's Health Study, we evaluated evidence for a major
      gene after allowing for measured environmental risk factors. Two hundred sixty
      five incident breast cancer probands were identified from a prospective cohort
      study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree
      development form was mailed to the probands to ascertain all first-degree female
      relatives. A questionnaire and body measurement protocol were mailed to
      identified living relatives or surrogates. Segregation analyses were conducted on
      a total of 1,145 women in 251 families using regressive models as implemented in
      S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier
      age-at-onset provided the best fit to the data. Incorporation of measured
      environmental risk factors as covariates yielded no significant improvements in
      the likelihoods. Approximately 50% of this population could be expected to carry
      a late-onset breast cancer susceptibility gene, and 23% of the population is
      susceptible because of the environment in which they live. Homozygous gene
      carriers are predicted to have a mean age-at-onset of 48 years, over 20 years
      earlier than heterozygotes; few cases would be expected among non-gene carriers.
      In conclusion, the transmission pattern of late-onset breast cancer may be
      determined by a common susceptibility gene.

PMID- 8536958
TI  - Epidemiologic and genetic follow-up study of 544 Minnesota breast cancer
      families: design and methods.
AB  - In 1944, a case-control family study was initiated at the Dight Institute for
      Human Genetics at the University of Minnesota to study the influences of
      childbearing breastfeeding, and hereditary susceptibility on the occurrence and
      age-of-onset of breast cancer. Index cases (probands) were women ascertained at
      the Tumor Clinic of the University of Minnesota Hospital. Medical history and
      life style information were obtained on probands and relatives, and all cancers
      were histologically verified. A total of 544 families were studied, with probands
      diagnosed between 1931 and 1952. All of the records and pathology slides have
      been maintained from the original study; for most probands this includes the
      original tissue blocks. We are conducting a historical cohort study of selected
      of selected first- and second-degree female relatives (sisters, daughters,
      nieces, granddaughters) of the probands and a group of control women identified
      as the spouses of all male first- and second-degree relatives (brothers, sons,
      grandsons, and nephews). The subsequent development of breast cancer is being
      determined to quantify the absolute risk associated with a positive family
      history. Current disease status is ascertained with mammography, and stromal
      density is measured using digital imaging. Segregation analysis will be applied
      to examine how non-genetic factors such as diet, exogenous hormone use, and body
      fat distribution influence risk in women at high risk because of family history.
      A subset of families are being selected for molecular analysis of the BRCA1 gene
      or for linkage analyses to identify putative susceptibility loci other than
      BRCA1. Documented cancer histories were known for at least three generations, and
      the current study extends the pedigrees up to four or five generations for every
      family, allowing a detailed description of familial risk. This cohort study of
      breast cancer families is likely to be important in both quantity and quality of
      data and will serve as a major genetic epidemiologic resource, being free of
      selection bias and having relevant non-genetic exposure determined in at least
      four generations.

PMID- 8536959
TI  - Charlotte Auerbach (1899-1994).

PMID- 8536960
TI  - Extragenic suppressors of Schizosaccharomyces pombe rad9 mutations uncouple
      radioresistance and hydroxyurea sensitivity from cell cycle checkpoint control.
AB  - Schizosaccharomyces pombe cells that contain a mutation within rad9 are sensitive
      to ionizing radiation, UV light and hydroxyurea, relative to wild-type strains.
      In addition, the mutants are moderately hypomutable by UV and unable to delay
      initiation of mitosis after treatment with radiation or hydroxyurea. Three
      radioresistant derivatives of rad9::ura4 cells were isolated, and each contained
      a single unique extragenic suppressor responsible for the acquired resistance.
      The suppressor loci also conferred radioresistance upon cells containing rad9
      192, which differs from rad9+ by a single base pair change. The suppressors
      additionally enhanced the radioresistance of cells containing rad3-136, a
      mutation that leads to phenotypes similar to those mediated by rad9::ura4. None
      of the derivatives of rad9::ura4 cells recovered the ability to delay cycling in
      G2 after exposure to ionizing radiation or UV light. All three suppressor
      derivatives, relative to the parental rad9::ura4 strain, also exhibited a
      moderate increase in resistance to the DNA replication inhibitor hydroxyurea
      without gaining the ability to stop progression into mitosis despite the
      inhibition of DNA synthesis. Results are discussed in terms of models to explain
      the putative role of rad9 and the suppressor genes in promoting radioresistance
      and mediating checkpoint controls responsive to DNA damage or incomplete DNA
      replication.

PMID- 8536961
TI  - Species-specific and mating type-specific DNA regions adjacent to mating type
      idiomorphs in the genus Neurospora.
AB  - Mating type idiomorphs control mating and subsequent sexual development in
      Neurospora crassa and were previously shown to be well conserved in other
      Neurospora species. The centromere-proximal flanks of the A and a idiomorphs, but
      not the distal flanks from representative heterothallic, pseudohomothallic, and
      homothallic Neurospora species contain apparent species-specific and/or mating
      type-specific sequences adjacent to the well-conserved idiomorphs. The variable
      flank is bordered by regions that are highly homologous in all species. The
      sequence of approximately 1 kb immediately flanking the conserved idiomorphs of
      each species was determined. Sequence identity between species ranged from 20%
      (essentially unrelated) to > 90%. By contrast, the mt-A1 gene shows 88-98%
      identity. Sequence and hybridization data also show that the centromere-proximal
      flanks are very different between the two mating types for N. intermedia, N.
      discreta, and N. tetrasperma, but not for N. sitophila and N. crassa. The data
      suggest a close evolutionary relationship between several of the species; this is
      suppported by phylogenetic analysis of their respective mt-A1 genes. The origin
      of the variable regions adjacent to the evolutionarily conserved mating type
      idiomorphs is unknown.

PMID- 8536962
TI  - Analysis of inbreeding depression in Agaricus bisporus.
AB  - Inbreeding depression was observed in the commercial button mushroom, Agaricus
      bisporus, by examining two laboratory populations. The outbred population
      consisted of 20 compatible pairings, 10 homokaryons with each of the homokaryons
      Ag1-1 and Ag89-65. The inbred population consisted of 104 backcrosses (among
      which 52 were expected to be sexually compatible) obtained from the pairings of
      two progenitor homokaryons, Ag1-1 and Ag89-65, with 52 progeny homokaryons
      derived from the mating between Ag1-1 and Ag89-65. The eight fitness components
      examined for these two populations were successful matings as identified by the
      analysis of restriction fragment length polymorphisms, positive mycelial
      interaction in these successful matings, heterokaryon growth rate, primordium
      formation by the successful matings, fertile fruiting body formation, time to
      first break, average number of fruiting bodies per square foot, and average
      weight per fruiting body. The outcrossed population showed a significant
      advantage over the inbred population in three of eight fitness components. Two
      pairs of traits were significantly correlated. The multiplicative fitness ratio
      of the inbred to the outcrossed population was 0.18. The relevance of inbreeding
      depression to the evolution of fungal mating systems and to mushroom breeding is
      discussed.

PMID- 8536963
TI  - Integrated maps of the chromosomes in Dictyostelium discoideum.
AB  - Detailed maps of the six chromosomes that carry the genes of Dictyostelium
      discoideum were constructed by correlating physically mapped regions with
      parasexually determined linkage groups. Chromosomally assigned regions were
      ordered and positioned by the pattern of altered fragment sizes seen in a set of
      restriction enzyme mediated integration-restriction fragment length polymorphism
      (REMI-RFLP) strains each harboring an inserted plasmid that carries sites
      recognized by NotI, SstI, SmaI, BglI and ApaI. These restriction enzymes were
      used to digest high molecular weight DNA prepared from more than 100 REMI-RFLP
      strains and the resulting fragments were separated and sized by pulsed-field
      gels. More than 150 gene probes were hybridized to blots of these gels and used
      to map the insertion sites relative to flanking restriction sites. In this way,
      we have been able to restriction map the 35 mb genome as well as determine the
      map position of more than 150 genes to with approximately 40 kb resolution. These
      maps provide a framework for subsequent refinement.

PMID- 8536964
TI  - Correlation of Rhs elements with Escherichia coli population structure.
AB  - The Rhs family of composite genetic elements was assessed for variation among
      independent Escherichia coli strains of the ECOR reference collection. The
      location and content of the RhsA-B-C-F subfamily correlates highly with the
      clonal structure of the ECOR collection. This correlation exists at several
      levels: the presence of Rhs core homology in the strain, the location of the Rhs
      elements present, and the identity of the Rhs core-extensions associated with
      each element. A provocative finding was that an identical 1518-bp segment,
      covering core-extension-b1 and its associated downstream open reading frame, is
      present in two distinct clonal groups, but in association with different Rhs
      elements. The sequence identity of this segment when contrasted with the
      divergence of other chromosomal segments suggests that shuffling of Rhs core
      extensions has been a relatively recent variation. Nevertheless the copies of
      core-extension-b1 were placed within the respective Rhs elements before the
      emergence of the clonal groups. In the course of this analysis, two new Rhs
      elements absent from E. coli K-12 were discovered: RhsF, a fourth member of the
      RhsA-B-C-F subfamily, and RhsG, the prototype of a third Rhs subfamily.

PMID- 8536965
TI  - Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis
      elegans.
AB  - The genetic map of each Caenorhabditis elegans chromosome has a central gene
      cluster (less pronounced on the X chromosome) that contains most of the
      mutationally defined genes. Many linkage group termini also have clusters, though
      involving fewer loci. We examine the factors shaping the genetic map by analyzing
      the rate of recombination and gene density across the genome using the positions
      of cloned genes and random cDNA clones from the physical map. Each chromosome has
      a central gene-dense region (more diffuse on the X) with discrete boundaries,
      flanked by gene-poor regions. Only autosomes have reduced rates of recombination
      in these gene-dense regions. Cluster boundaries appear discrete also by
      recombination rate, and the boundaries defined by recombination rate and gene
      density mostly, but not always, coincide. Terminal clusters have greater gene
      densities than the adjoining arm but similar recombination rates. Thus, unlike in
      other species, most exchange in C. elegans occurs in gene-poor regions. The
      recombination rate across each cluster is constant and similar; and cluster size
      and gene number per chromosome are independent of the physical size of
      chromosomes. We propose a model of how this genome organization arose.

PMID- 8536966
TI  - Heritability and selection on body size in a natural population of Drosophila
      buzzatii.
AB  - An attempt was made to assess whether the phenotypic differences in body size (as
      measured by wing length) between wild-caught mating and single Drosophila
      buzzatii males could be attributed to genetic differences between the samples.
      Mating males were found to be larger and less variable than a random sample of
      the population. The progeny of the mating males (produced by crossing to a random
      female from a stock derived from the same population) were on average larger than
      those of the single males, but not significantly so (P = 0.063), and less
      phenotypically variable. This difference in variance between the samples suggests
      that there are indeed genetic differences between the paternal samples but tests
      for significant differences in the additive genetic component of variance proved
      inconclusive. For both samples it was found that while the ratio of additive
      genetic variation in the laboratory to phenotypic variation in the field yielded
      estimates of hs2(N) congruent to 10% the regression of offspring reared in the
      laboratory on parents from the wild was not significantly different from zero. In
      addition, it was found that the average development time of the progeny of the
      mating males is shorter than that of the random sample.

PMID- 8536967
TI  - Developmental analysis of the ovarian tumor gene during Drosophila oogenesis.
AB  - Severe alleles of the ovarian tumor (otu) and ovo genes result in female
      sterility in Drosophila melanogaster, producing adult ovaries that completely
      lack egg chambers. We examined the developmental stage in which the agametic
      phenotype first becomes apparent. Germ cell development in embryos was studied
      using a strategy that allowed simultaneous labeling of pole cells with the
      determination of embryonic genotype. We found that ovo- or otu- XX embryonic germ
      cells were indistinguishable in number and morphology from those present in wild
      type siblings. The effects of the mutations were not consistently manifested in
      the female germline until pupariation, and there was no evidence that either gene
      was required for germ cell viability at earlier stages of development. The
      requirement for otu function in the pupal and adult ovary is supported by
      temperature-shift experiments using a heat-inducible otu gene construct. We
      demonstrate that otu activity limited to prepupal stages was not sufficient to
      support oogenesis, while induction during the pupal and adult periods caused
      suppression of the otu mutant phenotype.

PMID- 8536968
TI  - Conserved alternative splicing patterns and splicing signals in the Drosophila
      sodium channel gene para.
AB  - We cloned genomic DNA corresponding to the Drosophila virilis homologue of para,
      a gene encoding a sodium channel alpha-subunit, and obtained many partial cDNA
      clones from embryos and adults. Para protein has been well conserved, and the
      optional elements at six different sites of alternative splicing in D.
      melanogaster are present in D. virilis, in addition to one new optional exon.
      Among 31 different splice-types observed in D. virilis, the stage-specific
      pattern of alternative splicing seen in D. melanogaster is also conserved.
      Comparison of genomic DNA sequence revealed three aspects that vary between
      alternatively and constitutively used exon sequences. Sixteen short blocks (10-75
      bp), the only recognizably conserved intron sequence, were disproportionately
      associated with alternatively used splice sites. Silent site substitutions were
      found much less frequently in alternative than constitutive exon elements, and
      the degree of match to the Drosophila splice site consensus tended to be lower at
      less frequently selected alternative splice junctions. This study shows that the
      developmentally regulated variability of para products is highly conserved and
      therefore likely to be of functional significance and suggests that a variety of
      different sequence-dependent mechanisms may regulate this pattern of alternative
      splicing.

PMID- 8536969
TI  - Nucleotide polymorphism in the 5' promoter region of esterase 6 in Drosophila
      melanogaster and its relationship to enzyme activity variation.
AB  - A 974-bp region immediately 5' of the esterase 6 gene was sequenced in 17 field
      derived third chromosome isoallelic lines. Twenty-three polymorphisms were
      identified, only two in the first 400 bp 5' but 16 in a 325-bp region from -494
      to -819 bp. This distribution differs from previously published patterns in
      Drosophila simulans and D. mauritiana, where the first 800 bp are highly
      conserved. Fourteen common polymorphisms in the 325-bp region above are all in
      strong linkage disequilibrium with each other. Moreover, most of the haplotypes
      defined by the total of 23 polymorphisms fall into two groups that differ as a
      block at all 14 of these latter sites. Sequence differences between the two
      groups include some restriction sites that were scored in an earlier study of
      RFLPs and EST6 enzyme phenotypes among 42 isoallelic lines from the same
      population. By collating the two studies, we show that one haplotype group yields
      approximately 15% lower EST6 enzyme activity in adult males than the other. The
      promoter haplotypes show only weak disequilibrium with the esterase 6 fast/slow
      allozyme polymorphism, so it seems unlikely that previously reported latitudinal
      clines in the allozyme frequencies are due to their hitchhiking along with
      selection on the promoter difference.

PMID- 8536970
TI  - Molecular evolution of the duplicated Amy locus in the Drosophila melanogaster
      species subgroup: concerted evolution only in the coding region and an excess of
      nonsynonymous substitutions in speciation.
AB  - From the analysis of restriction maps of the Amy region in eight sibling species
      belonging to the Drosophila melanogaster species subgroup, we herein show that
      the patterns of duplication of the Amy gene are almost the same in all species.
      This indicates that duplication occurred before speciation within this species
      subgroup. From the nucleotide sequence data, we show a strong within-species
      similarity between the duplicated loci in the Amy coding region. This is in
      contrast to a strong similarity in the 5' and 3' flanking regions within each
      locus (proximal or distal) throughout the species subgroup. This means that
      concerted evolution occurred only in the Amy coding region and that
      differentiated evolution between the duplication occurred in the flanking
      regions. Moreover, when comparing the species, we also found a significant excess
      of nonsynonymous substitutions. In particular, all the fixed substitutions
      specific to D. erecta were found to be nonsynonymous. We thus conclude that
      adaptive protein evolution occurred in the lineage of D. erecta that is a
      "specialist" species for host plants and probably also occurs in the process of
      speciation in general.

PMID- 8536971
TI  - Evolutionary relationships and sequence variation of alpha-amylase variants
      encoded by duplicated genes in the Amy locus of Drosophila melanogaster.
AB  - To infer the genealogical relationships of alpha-amylase electromorphs of
      Drosophila melanogaster, we determined the nucleotide sequences of a collection
      of electromorphs sampled throughout the world. On average there were 1.0 amino
      acid substitutions between identical electromorphs and 3.9 between different
      electromorphs, respectively. We found that the evolution of AMY1 through AMY6
      electromorphs occurred by sequential accumulation of single amino acid
      substitutions each causing one charge difference. The nucleotide diversities at
      synonymous sites within Amy1,Amy2,Amy3,Amy4 and Amy6 were 0.0321, 0.0000, 0.0355,
      0.0059 and 0.0030, respectively. We also obtained evidence of genetic exchanges,
      such as intrachromosomal recombination, interchromosomal recombination or gene
      conversion, between the two duplicated Amy genes as well as among the alleles.

PMID- 8536972
TI  - Mutations of zeste that mediate transvection are recessive enhancers of position
      effect variegation in Drosophila melanogaster.
AB  - Evidence is presented demonstrating that mutations of zeste, particularly the
      null state, are strong recessive enhancers of position-effect variegation (PEV)
      for the white, roughest and Notch loci. The zeste locus encodes a DNA-binding
      protein that acts as a transcription factor and mediates transvection phenomena
      at several loci. Its involvement with these seemingly diverse phenomena suggests
      that the normal zeste product functions in the decondensation of chromatin. A
      model is presented proposing that zeste is important for opening and stabilizing
      domains of chromatin, a step in gene determination and the establishment of cell
      memory. It postulates that chromatin domains that have been structurally modified
      by chromosomal rearrangement or by insertion of transposable elements are
      particularly sensitive to the absence or modification of the zeste protein. Such
      a view unifies the role of zeste in transcription, transvection and PEV.

PMID- 8536973
TI  - Genetic analysis of the colicin V secretion pathway.
AB  - Colicin V (ColV) is peptide antibiotic secreted by Escherichia coli through a
      dedicated exporter composed of three proteins, CvaA, CvaB, and TolC. ColV
      secretion is independent of the E. coli general secretory pathway (Sec) but
      requires an N-terminal export signal specific for the CvaAB/TolC exporter. ColV
      secretion was characterized using genetic and biochemical methods. When the ColV
      N-terminal extension is replaced with the OmpA signal sequence, the Sec system
      can localize ColV to the periplasm. Periplasmic ColV is lethal to cells lacking
      the ColV immunity protein, Cvi. Based on this result, a genetic assay was
      designed to monitor for the presence of periplasmic ColV during normal CvaAB/TolC
      mediated secretion. Results indicate that low levels of ColV may be present in
      the periplasm during secretion. Precursor and mature ColV were also characterized
      from the wild-type system and in various exporter mutant backgrounds using
      immunoprecipitation. ColV processing is rapid in wild-type cells, and CvaA and
      CvaB are critical for processing to occur. In contrast, processing occurs
      normally, albeit more slowly, in a TolC mutant.

PMID- 8536974
TI  - Molecular basis of polymorphism at the esterase-5B locus in Drosophila
      pseudoobscura.
AB  - Sequence variation was studied in a 2.2-kb region encompassing the esterase-5B
      locus in Drosophila pseudoobscura from two California populations. In these
      populations, two common electrophoretic classes and many less frequent variants
      occur, and it was formerly shown by KEITH (1983) that allele frequencies differed
      from random distribution under an infinite allele model. Nucleotide polymorphisms
      were determined in 16 sequences representing 14 electrophoretic classes. There
      was no significant sequence differentiation between populations, and both
      synonymous and nonsynonymous polymorphisms are distributed homogeneously along
      the sequence. The data show that the two major electrophoretic classes are
      heterogeneous at the amino acid level with no diagnostic amino acid(s)
      distinguishing them. At the nucleotide level, members of one major class are more
      similar to members of other electrophoretic classes than they are to each other.
      It appears that random combinations of the neutral amino acid polymorphisms and
      other undefined physical properties of the proteins generate the different
      electrophoretic classes and maintain considerable variation at Est-5B.

PMID- 8536975
TI  - Chaser (Csr), a new gene affecting larval foraging behavior in Drosophila
      melanogaster.
AB  - Chaser (Csr) was uncovered in a gamma mutagenesis screen to identify genes that
      modify the larval foraging behavior of sitters to rovers. Rover larvae have
      significantly longer path lengths than sitters while foraging on a yeast and
      water paste. This difference is influenced by one major gene, foraging (for),
      which has two naturally occurring alleles, forR (rover) and fors (sitter). In a
      mutagenesis screen for modifiers of for, we identified three lines with viable
      mutations on chromosome 3 that alter foraging behavior. Each of these mutations
      increased larval path lengths in fors/fors larvae in a dominant fashion, and were
      not separable by recombination. These mutations are therefore probably allelic
      and define a new gene that we have called Csr. Csr was genetically localized
      using the lethal-tagging technique. This technique resulted in seven lines with a
      significant decrease in larval path-length and recessive lethal mutations on
      chromosome 3. We refer to these as reverted Csr (Csrrv) lines. Deficiencies that
      uncovered cytologically visible chromosome rearrangements in three of the seven
      reverted lines were used in a complementation analysis. In this way we mapped the
      lethal mutations in the Csrrv lines to cytological region 95F7-96A1 on the right
      arm of chromosome 3.

PMID- 8536976
TI  - The tolkin gene is a tolloid/BMP-1 homologue that is essential for Drosophila
      development.
AB  - The Drosophila decapentaplegic (dpp) gene, a member of the transforming growth
      factor beta superfamily of growth factors, is critical for specification of the
      embryonic dorsal-ventral axis, for proper formation of the midgut, and for
      formation of Drosophila adult structures. The Drosophila tolloid gene has been
      shown to genetically interact with dpp. The genetic interactions between tolloid
      and dpp suggests a model in which the tolloid protein participates in a complex
      containing the DPP ligand, its protease serving to activate DPP, either directly
      or indirectly. We report here the identification and cloning of another
      Drosophila member of the tolloid/bone morphogenic protein (BMP) 1 family, tolkin,
      which is located 700 bp 5' to tolloid. Its overall structure is like tolloid,
      with an N-terminal metalloprotease domain, five complement subcomponents C1r/C1s,
      Uegf, and Bmp1 (CUB) repeats and two epidermal growth factor (EGF) repeats. Its
      expression pattern overlaps that of tolloid and dpp in early embryos and diverges
      in later stages. In larval tissues, both tolloid and tolkin are expressed
      uniformly in the imaginal disks. In the brain, both tolloid and tolkin are
      expressed in the outer proliferation center, whereas tolkin has another stripe of
      expression near the outer proliferation center. Analysis of lethal mutations in
      tolkin indicate it is vital during larval and pupal stages. Analysis of its
      mutant phenotypes and expression patterns suggests that its functions may be
      mostly independent of tolloid and dpp.

PMID- 8536977
TI  - Islands of complex DNA are widespread in Drosophila centric heterochromatin.
AB  - Heterochromatin is a ubiquitous yet poorly understood component of multicellular
      eukaryotic genomes. Major gaps exist in our knowledge of the nature and overall
      organization of DNA sequences present in heterochromatin. We have investigated
      the molecular structure of the 1 Mb of centric heterochromatin in the Drosophila
      minichromosome Dp1187. A genetic screen of irradiated minichromosomes yielded
      rearranged derivatives of Dp1187 whose structures were determined by pulsed-field
      Southern analysis and PCR. Three Dp1187 deletion derivatives and an inversion had
      one breakpoint in the euchromatin and one in the heterochromatin, providing
      direct molecular access to previously inaccessible parts of the heterochromatin.
      End-probed pulsed-field restriction mapping revealed the presence of at least
      three "islands" of complex DNA, Tahiti, Moorea, and Bora Bora, constituting
      approximately one half of the Dp1187 heterochromatin. Pulsed-field Southern
      analysis demonstrated that Drosophila heterochromatin in general is composed of
      alternating blocks of complex DNA and simple satellite DNA. Cloning and
      sequencing of a small part of one island, Tahiti, demonstrated the presence of a
      retroposon. The implications of these findings to heterochromatin structure and
      function are discussed.

PMID- 8536978
TI  - Complete sequence of the mitochondrial DNA of the annelid worm Lumbricus
      terrestris.
AB  - We have determined the complete nucleotide (nt) sequence of the mitochondrial
      genome of an oligochaete annelid, the earthworm Lumbricus terrestris. This genome
      contains the 37 genes typical of metazoan mitochondrial DNA (mtDNA), including
      ATPase8, which is missing from some invertebrate mtDNAs. ATPase8 is not
      immediately upstream of ATPase6, a condition found previously only in the mtDNA
      of snails. All genes are transcribed from the same DNA strand. The largest
      noncoding region is 384 nt and is characterized by several homopolymer runs, a
      tract of alternating TA pairs, and potential secondary structures. All protein
      encoding genes either overlap the adjacent downstream gene or end at an
      abbreviated stop codon. In Lumbricus mitochondria, the variation of the genetic
      code that is typical of most invertebrate mitochondrial genomes is used. Only the
      codon ATG is used for translation initiation. Lumbricus mtDNA is A + T rich,
      which appears to affect the codon usage pattern. The DHU arm appears to be
      unpaired not only in tRNAser(AGN), as is typical for metazoans, but perhaps also
      in tRNAser(UCN), a condition found previously only in a chiton and among
      nematodes. Relating the Lumbricus gene organization to those of other major
      protostome groups requires numerous rearrangements.

PMID- 8536979
TI  - Phenotypic and molecular analysis of a transgenic insertional allele of the mouse
      Fused locus.
AB  - Spontaneous mutations at the mouse Fused (Fu) locus cause dominant skeletal and
      neurological defects and recessive lethal embryonic defects including
      neuroectodermal abnormalities and axial duplications. Here, we describe a new
      allele at the Fu locus caused by a transgenic insertional mutation, H epsilon 46.
      Embryos homozygous for the H epsilon 46 insertion die at day 9-10 post coitum and
      display phenotypic defects similar to those associated with Fu alleles. The H
      epsilon 46 locus was cloned and shown to contain a 20-kb deletion at the site of
      transgene insertion with no other detectable rearrangements. Genomic probes from
      the H epsilon 46 locus were mapped to a genetic locus closely linked to Fu on
      chromosome 17 and were hybridized to a YAC contig covering the FuKi critical
      region. Compound heterozygotes between H epsilon 46 and FuKi were inviable and
      displayed abnormalities at the same stage of embryogenesis as do homozygotes for
      either of the two mutations, demonstrating that these two recessive lethal
      mutations belong to the same complementation group. A genomic probe from the wild
      type H epsilon 46 locus detected a transcript that is disrupted by the transgenic
      insertion, representing a candidate for the wild-type allele of Fused.

PMID- 8536980
TI  - Active and inactive transplacement of the M26 recombination hotspot in
      Schizosaccharomyces pombe.
AB  - The ade6-M26 mutation of the fission yeast Schizosaccharomyces pombe creates a
      meiotic recombination hotspot that elevates ade6 intragenic recombination
      approximately 10-15-fold. A heptanucleotide sequence including the M26 point
      mutation is required but not sufficient for hotspot activity. We studied the
      effects of plasmid and chromosomal context on M26 hotspot activity. The M26
      hotspot was inactive on a multicopy plasmid containing M26 embedded within 3.0 or
      5.9 kb of ade6 DNA. Random S. pombe genomic fragments totaling approximately 7 Mb
      did not activate the M26 hotspot on a plasmid. M26 hotspot activity was
      maintained when 3.0-, 4.4-, and 5.9-kb ade6-M26 DNA fragments, with various
      amounts of non-S. pombe plasmid DNA, were integrated at the ura4 chromosomal
      locus, but only in certain configurations relative to the ura4 gene and the
      cointegrated plasmid DNA. Several integrations created new M26-independent
      recombination hotspots. In all cases the non-ade6 DNA was located > 1 kb from the
      M26 site, and in some cases > 2 kb. Because the chromosomal context effect was
      transmitted over large distances, and did not appear to be mediated by a single
      discrete DNA sequence element, we infer that the local chromatin structure has a
      pronounced effect on M26 hotspot activity.

PMID- 8536981
TI  - teosinte branched1 and the origin of maize: evidence for epistasis and the
      evolution of dominance.
AB  - Two quantitative trait loci (QTL) controlling differences in plant and
      inflorescence architecture between maize and its progenitor (teosinte) were
      analyzed. Complementation tests indicate that one of these, which is on
      chromosome arm 1L, is the locus for the maize mutant teosinte branched1 (tb1).
      This QTL has effects on inflorescence sex and the number and length of internodes
      in the lateral branches and inflorescences. This QTL has strong phenotypic
      effects in teosinte background but reduced effects in maize background. The
      second QTL, which is on chromosome arm 3L, affects the same traits as the QTL on
      1L. We identify two candidate loci for this QTL. The effects of this QTL on
      several traits are reduced in both maize and teosinte background as compared to a
      maize-teosinte F2 population. Genetic background appears to affect gene action
      for both QTL. Analysis of a population in which both QTL were segregating
      revealed that they interact epistatically. Together, these two QTL substantially
      transform both plant and inflorescence architecture. We propose that tb1 is
      involved in the plant's response to local environment to produce either long or
      short branches and that maize evolution involved a change at this locus to
      produce short branches under all environments.

PMID- 8536982
TI  - Molecular organization and germinal instability of R-stippled maize.
AB  - The spotted seed allele R-stippled (R-st) is comprised of the following genetic
      components: strong seed color (Sc), inhibitor-of-R (I-R) and near-colorless seed
      (Nc). I-R is a mobile element that represses (Sc) expression irregularly.
      Germinal I-R losses produce progeny with fully colored seed. Southern blot
      analysis revealed four r-hybridizing segments in R-st and three, two or one in
      two sets of unequal crossover deletion products. By comparison to published
      reports of r gene structure, we maintain that each segment contains at least one
      r gene. The proximal r gene, Sc, confers strong seed color; the three distal r
      genes together produce near-colorless seed. R-st's seed spotting phenotype is
      correlated with the presence of a 3.3-kb insert in Sc identified as I-R. The
      level of the near-colorless phenotype is inversely correlated with the number of
      r genes present, suggesting involvement of a multiple copy silencing mechanism in
      their regulation. Phenotypic changes in R-st occurred primarily by unequal
      exchange between r genes. The locations of exchange positions showed a strong
      polarity, nearly all occurring in the 3' portions of the identified r genes.

PMID- 8536984
TI  - New rust resistance specificities associated with recombination in the Rp1
      complex in maize.
AB  - We address the question of whether genetic reassortment events, including unequal
      crossing over and gene conversion, at the Rp1 complex are capable of generating
      novel resistance specificities that were not present in the parents. Some 176
      events involving genetic reassortment within the Rp1 complex were screened for
      novel resistance specificities with a set of 11 different rust biotypes. Most
      (150/176) of the events were susceptible to all tested rust biotypes, providing
      no evidence for new specificities. Eleven events selected as double-resistant
      recombinants, when screened with the 11 test biotypes, showed the combined
      resistance of the two parental types consistent with a simple recombination and
      pyramiding of the parental resistances. Nine events selected either as having
      partial resistance or complete susceptibility to a single biotype possessed
      resistance to a subset of the biotypes that the parents were resistant to,
      suggesting segregation of resistance genes present in the parental Rp1 complex.
      Four events gave rise to novel specificities being resistant to at least one rust
      biotype to which both parents were susceptible. All four had flanking marker
      exchange, demonstrating that crossing over within the Rp1 complex is associated
      with the appearance of new rust resistance specificities.

PMID- 8536983
TI  - Organization of paramutagenicity in R-stippled maize.
AB  - In heterozygotes, R-stippled (R-st) reduces the pigmenting potential of sensitive
      r alleles heritably (paramutation). R-st is comprised of four r genes arranged in
      direct orientation. Unequal crossing over within R-st generates deletion products
      retaining from one to three r genes. Paramutagenic strength decreased in parallel
      with copy number, both among internal and distal deletions. Single-gene R-st
      derivatives were nonparamutagenic. This was so whether or not the single gene
      retained the transposable element (I-R) responsible for seed spotting. Adding
      back r genes by intragenic recombination increased paramutagenicity in proportion
      to total gene number. Each member of a set of overlapping deletions retained
      moderately strong activity, showing that no single r gene or intragenic region is
      required for paramutagenicity. Proximal and distal loss R-st derivatives, each
      retaining two r genes, were less paramutagenic in trans than the corresponding
      four copy cis combination, indicating R-st's paramutagenic determinants function
      as a cis-interdependent unit in bringing about modification of a sensitive
      allele.

PMID- 8536985
TI  - Distribution of unlinked transpositions of a Ds element from a T-DNA locus on
      tomato chromosome 4.
AB  - In maize, receptor sites for unlinked transpositions of Activator (Ac) elements
      are not distributed randomly. To test whether the same is true in tomato, the
      receptor sites for a Dissociation (Ds) element derived from Ac, were mapped for
      26 transpositions unlinked to a donor T-DNA locus on chromosome 4. Four
      independent transposed Dss mapped to sites on chromosome 4 genetically unlinked
      to the donor T-DNA, consistent with a preference for transposition to unlinked
      sites on the same chromosome as opposed to sites on other chromosomes. There was
      little preference among the nondonor chromosomes, except perhaps for chromosome
      2, which carried seven transposed Dss, but these could not be proven to be
      independent. However, these data, when combined with those from other studies in
      tomato examining the distribution of transposed Acs or Dss among nondonor
      chromosomes, suggest there may be absolute preferences for transposition
      irrespective of the chromosomal location of the donor site. If true,
      transposition to nondonor chromosomes in tomato would differ from that in maize,
      where the preference seems to be determined by the spatial arrangement of
      chromosomes in the interphase nucleus. The tomato lines carrying Ds elements at
      known locations are available for targeted transposon tagging experiments.

PMID- 8536986
TI  - Comparative analysis of QTLs affecting plant height and maturity across the
      Poaceae, in reference to an interspecific sorghum population.
AB  - Correspondence among QTLs affecting height and/or flowering was investigated
      across the five races of sorghum, an interspecific sorghum F2 population, and 32
      previously published sorghum, maize, rice, wheat, and barley populations
      revealing 185 QTLs or discrete mutants. Among nine QTLs mapped in the
      interspecific sorghum population (six affecting height and three affecting
      flowering), at least seven (78%) are associated with "conversion," backcross
      introgression of alleles imparting reduced height or earlier flowering from
      cultivated sorghums into one or more exotic Sorghum bicolor races. One
      chromosomal region was "converted" in all S. bicolar races--in the interspecific
      F2, this region explained 54.8% of height variation (putatively the Dw2 gene) and
      85.7% of flowering time variation (putatively Ma1). Comparative data suggest that
      Ma1 and Dw2 orthologs influence height and flowering of other Poaceae taxa and
      support classical dogma that the sorghum phenotypes attributed to Ma1 and Dw2
      (respectively) are due to different genetic loci. Other sorghum QTLs also showed
      correspondence with those in other Poaceae, more frequently than would be
      expected by chance. Possible homoeologous QTLs were found within both the maize
      and sorghum genomes. Comparative QTL mapping provides a means to unify, and
      thereby simplify, molecular analysis of complex phenotypes.

PMID- 8536988
TI  - Muller's ratchet, epistasis and mutation effects.
AB  - In this study, computer simulation is used to show that despite synergistic
      epistasis for fitness, Muller's ratchet can lead to lethal fitness loss in a
      population of asexuals through the accumulation of deleterious mutations. This
      result contradicts previous work that indicated that epistasis will halt the
      ratchet. The present results show that epistasis will not halt the ratchet
      provided that rather than a single deleterious mutation effect, there is a
      distribution of deleterious mutation effects with sufficient density near zero.
      In addition to epistasis and mutation distribution, the ability of Muller's
      ratchet to lead to the extinction of an asexual population under epistasis for
      fitness depends strongly on the expected number of offspring that survive to
      reproductive age. This strong dependence is not present in the nonepistatic model
      and suggests that interpreting the population growth parameter as fecundity is
      inadequate. Because a continuous distribution of mutation effects is used in this
      model, an emphasis is placed on the dynamics of the mutation effect distribution
      rather than on the dynamics of the number of least mutation loaded individuals.
      This perspective suggests that current models of gene interaction are too simple
      to apply directly to long-term prediction for populations undergoing the ratchet.

PMID- 8536987
TI  - Properties of statistical tests of neutrality for DNA polymorphism data.
AB  - A class of statistical tests based on molecular polymorphism data is studied to
      determine size and power properties. The class includes Tajima's D statistic as
      well as the D* and F* tests proposed by Fu and Li. A new method of constructing
      critical values for these tests is described. Simulations indicate that Tajima's
      test is generally most powerful against the alternative hypotheses of selective
      sweep, population bottleneck, and population subdivision, among tests within this
      class. However, even Tajima's test can detect a selective sweep or bottleneck
      only if it has occurred within a specific interval of time in the recent past or
      population subdivision only when it has persisted for a very long time. For
      greatest power against the particular alternatives studied here, it is better to
      sequence more alleles than more sites.

PMID- 8536990
TI  - The rec8 gene of Schizosaccharomyces pombe is involved in linear element
      formation, chromosome pairing and sister-chromatid cohesion during meiosis.
AB  - The fission yeast Schizosaccharomyces pombe does not form tripartite synaptonemal
      complexes during meiotic prophase, but axial core-like structures (linear
      elements). To probe the relationship between meiotic recombination and the
      structure, pairing, and segregation of meiotic chromosomes, we genetically and
      cytologically characterized the rec8-110 mutant, which is partially deficient in
      meiotic recombination. The pattern of spore viability indicates that chromosome
      segregation is affected in the mutant. A detailed segregational analysis in the
      rec8-110 mutant revealed more spores disomic for chromosome III than in a wild
      type strain. Aberrant segregations are caused by precocious segregation of sister
      chromatids at meiosis I, rather than by nondisjunction as a consequence of lack
      of crossovers. In situ hybridization further showed that the sister chromatids
      are separated prematurely during meiotic prophase. Moreover, the mutant forms
      aberrant linear elements and shows a shortened meiotic prophase. Meiotic
      chromosome pairing in interstitial and centromeric regions is strongly impaired
      in rec8-110, whereas the chromosome ends are less deficient in pairing. We
      propose that the rec8 gene encodes a protein required for linear element
      formation and that the different phenotypes of rec8-110 reflect direct and
      indirect consequences of the absence of regular linear elements.

PMID- 8536991
TI  - Emil Heitz (1892-1965): chloroplasts, heterochromatin, and polytene chromosomes.

PMID- 8536989
TI  - The yeast MER2 gene is required for chromosome synapsis and the initiation of
      meiotic recombination.
AB  - Mutation of the MER2 gene of Saccharomyces cerevisiae confers meiotic lethality.
      To gain insight into the function of the Mer2 protein, we have carried out a
      detailed characterization of the mer2 null mutant. Genetic analysis indicates
      that mer2 completely eliminates meiotic interchromosomal gene conversion and
      crossing over. In addition, mer2 abolishes intrachromosomal meiotic
      recombination, both in the ribosomal DNA array and in an artificial duplication.
      The results of a physical assay demonstrate that the mer2 mutation prevents the
      formation of meiosis-specific, double-strand breaks, indicating that the Mer2
      protein acts at or before the initiation of meiotic recombination. Electron
      microscopic analysis reveals that the mer2 mutant makes axial elements, which are
      precursors to the synaptonemal complex, but homologous chromosomes fail to
      synapse. Fluorescence in situ hybridization of chromosome-specific DNA probes to
      spread meiotic chromosomes demonstrates that homolog alignment is also
      significantly reduced in the mer2 mutant. Although the MER2 gene is transcribed
      during vegetative growth, deletion or overexpression of the MER2 gene has no
      apparent effect on mitotic recombination or DNA damage repair. We suggest that
      the primary defect in the mer2 mutant is in the initiation of meiotic genetic
      exchange.

PMID- 8536993
TI  - A Chlamydomonas genomic library in yeast artificial chromosomes.
AB  - We have constructed and characterized a Chlamydomonas reinhardtii total genomic
      library in yeast artificial chromosomes (YACs). The library contains 7500 clones
      with inserts ranging in size from 100-200 kb. The representation of the library
      was assessed by screening one-third of it with a probe derived from the dispersed
      repeat, Gulliver, which occurs approximately 13 times in the genome. At least 10
      of these Gulliver loci were isolated within 15 independent YACs. Two of these
      YACs encompass the Gulliver element designated G, which was reported to map to
      the uni linkage group (ULG). The end clones of these two YACs have been
      genetically mapped by RFLP analysis in an interspecific cross and thereby shown
      to be closely linked to the APM locus on the ULG. A third uni-specific YAC has
      also been isolated and its ends have been mapped by RFLP analysis. Genetic and
      RFLP analysis of these and other YACs indicates that the frequency of chimeric
      YACs in the library is very low. The library was constructed in a second
      generation vector that enables plasmid rescue of YAC end clones as well as copy
      number amplification of artificial chromosomes. We provide evidence that
      amplification of intact YACs requires a rad1:rad52 yeast strain.

PMID- 8536992
TI  - Heteroduplex DNA formation and homolog pairing in yeast meiotic mutants.
AB  - Previous studies of Saccharomyces cerevisiae have identified several meiosis
      specific genes whose products are required for wild-type levels of meiotic
      recombination and for normal synaptonemal complex (SC) formation. Several of
      these mutants were examined in a physical assay designed to detect heteroduplex
      DNA (hDNA) intermediates in meiotic recombination. hDNA was not detected in the
      rec102, mei4 and hop1 mutants; it was observed at reduced levels in red1, mek1
      and mer1 strains and at greater than the wild-type level in zip1. These results
      indicate that the REC102, MEI4, HOP1, RED1, MEK1 and MER1 gene products act
      before hDNA formation in the meiotic recombination pathway, whereas ZIP1 acts
      later. The same mutants assayed for hDNA formation were monitored for meiotic
      chromosome pairing by in situ hybridization of chromosome-specific DNA probes to
      spread meiotic nuclei. Homolog pairing occurs at wild-type levels in the zip1 and
      mek1 mutants, but is substantially reduced in mei4, rec102, hop1, red1 and mer1
      strains. Even mutants that fail to recombine or to make any SC or SC precursors
      undergo a significant amount of meiotic chromosome pairing. The in situ
      hybridization procedure revealed defects in meiotic chromatin condensation in
      mer1, red1 and hop1 strains.

PMID- 8536995
TI  - Metaphase karyotypes of fruit flies of Thailand. I. Five sibling species of the
      Bactrocera dorsalis complex.
AB  - Natural populations of fruit flies of the Bactrocera dorsalis complex exhibit
      chromosomal variation based on differences in the amount and distribution of
      constitutive heterochromatin in the centromeric regions of the autosomes and the
      sex chromosomes. The chromosomal variation, coupled with differences in external
      morphology and host plant specific preferences, strongly suggest the existence of
      5 closely related species within the B. dorsalis complex that have provisionally
      been designated B. dorsalis species B, C, D, and E in contrast with B. dorsalis
      s.s. (species A). Analysis of heterochromatin in autosomes and sex chromosomes
      has revealed 4 distinct groups of mitotic karyotypes. Bactrocera dorsalis is the
      only representative of Group I, which is characterized by the typical metacentric
      X chromosome and major blocks of centromeric heterochromatin in autosomes 5 and
      6. Group 2 consists of species B and C, which show prominent landmarks of
      pericentric heterochromatin in all autosomes and in the X chromosome. Group 3
      comprises species D, which is characterized by conspicuous blocks of pericentric
      heterochromatin in all autosomes but the long arm of the subtelocentric X
      chromosome is euchromatic and lacks a major portion of centromeric
      heterochromatin. Species E belongs to Group 4, which differs from Group 3 in
      having major blocks of heterochromatin at the distal portion of the X chromosome
      in addition to the prominent landmarks of pericentric heterochromatin in all
      autosomes. Chromosomal evolution among closely related species within the B.
      dorsalis complex clearly involves the presence or absence of constitutive
      heterochromatin in the centromeric regions of autosomes as well as in the X
      chromosome.

PMID- 8536996
TI  - Genetic differences in recombination frequency in the pig (Sus scrofa).
AB  - A comparison has been performed on 3 recently published linkage maps of the pig,
      hereafter designated as the American (A), European (E), and Swedish (S) maps. The
      cumulated distances between common markers in these 3 maps were in the ratio 1.00
      (A):0.88 (E):0.77 (S), in keeping with the ratio of the percentages of domestic
      genome in the reference families used to build the corresponding maps, i.e., 1.00
      (A):0.81 (E):0.50 (S). From further recombination frequencies reported in wild
      boars (in the S report), the wild pig genome length (in centimorgans) is expected
      to represent 66% of the domestic pig genome length. These observations tend to
      confirm a general result of Burt and Bell (Nature (London), 326: 803-805 (1987)),
      showing higher chiasma frequencies in domestic mammalian species compared with
      wild species. Consequences for mapping studies are discussed.

PMID- 8536994
TI  - 5 S rRNA is involved in fidelity of translational reading frame.
AB  - Chromosomal mutants (maintenance of frame = mof) in which the efficiency of -1
      ribosomal frameshifting is increased can be isolated using constructs in which
      lacZ expression is dependent upon a -1 shift of reading frame. We isolate a new
      mof mutation, mof9, in Saccharomyces cerevisiae and show that it is complemented
      by both single and multi-copy 5 S rDNA clones. Two independent insertion
      mutations in the rDNA locus (rDNA::LEU2 and rDNA::URA3) also display the Mof-
      phenotype and are also complemented by single and multi-copy 5 S rDNA clones.
      Mutant 5 S rRNAs expressed from a plasmid as 20-50% of total 5 S rRNA in a wild
      type host also induced the Mof- phenotype. The increase in frameshifting is
      greatest when the lacZ reporter gene is expressed on a high copy, episomal
      vector. No differences were found in 5 S rRNA copy number or electrophoretic
      mobilities in mof9 strains. Both mof9 and rDNA::LEU2 increase the efficiency of
      +1 frameshifting as well but have no effect on readthrough of UAG or UAA
      termination codons, indicating that not all translational specificity is
      affected. These data suggest a role for 5 S rRNA in the maintenance of frame in
      translation.

PMID- 8536997
TI  - Genetics of Glossina palpalis palpalis: designation of linkage groups and the
      mapping of eight biochemical and visible marker genes.
AB  - The loci for three enzymes (hexokinase, phosphoglucomutase, and testicular
      esterase) and two eye-color mutants (brick and tan) are mapped on the X
      chromosome of Glossina palpalis palpalis. The loci occur in the order brick Hex
      (tan/Pgm) Est-t, with a recombination frequency of approximately 78% between the
      outer two loci. The locus for octanol dehydrogenase is located in linkage group
      II and the loci for malate dehydrogenase and phosphoglucose isomerase are
      separated by a recombination frequency of about 42.5% in linkage group III.
      Intrachromosomal recombination occurs at a much lower frequency in males than in
      females. The distribution of five biochemical marker genes in the linkage groups
      of G. p. palpalis is markedly different from that found in other higher flies.

PMID- 8536998
TI  - Analysis of the distal 5' region of the human CYP17 gene.
AB  - In order to search for additional regulatory elements in the human CYP17 (steroid
      17 alpha-hydroxylase) gene and to compare it with potential regulatory elements
      in bovine CYP17 genes, 3.5 kb of 5' flanking region of CYP17 was cloned and
      analyzed. The newly acquired sequence was shown to be a highly defective copy of
      the human endogenous retrovirus HERV-K family. This retroviral sequence was
      itself interrupted by a novel element, a low copy number repeat occurring about
      20 times in the human genome, including a known copy in the human catechol-O
      methyltransferase gene. A reanalysis of the entire 5' flanking region of human
      CYP17 indicates that only the 300 bp immediately distal to the promoter is of
      unique sequence; other regulatory sequences, including any that are similar to
      the upstream region of the bovine genes, are unlikely to occur within 5.5 kb of
      the promoter.

PMID- 8536999
TI  - Molecular characterization and chromosome location of repeated DNA sequences in
      Hordeum species and in the amphiploid tritordeum (x Tritordeum Ascherson et
      Graebner).
AB  - Genomic DNA from 19 species and subspecies representing the four basic genomes
      (H, I, X, and Y) of Hordeum was restricted with HaeIII and hybridized with two
      repeated DNA sequences of Hordeum chilense. The potential use of repeated
      sequences in ascertaining genomic affinities within the genus Hordeum was studied
      by comparing restriction fragment patterns. The study demonstrated the following:
      (i) species that shared a basic genome showed more similar hybridization fragment
      patterns than species with different genomes, whether with pHch1 or pHch3; (ii)
      hybridization with pHch1 revealed the presence of certain fragments limited to
      the species with a H genome; and (iii) the alloploid nature of species like H.
      jubatum was confirmed. The chromosomal distribution of the two repeated sequences
      was studied in species representing each basic genome and in the amphiploid
      tritordeum using fluorescent in situ hybridization. No interspecific differences
      were found between the diploid species. In situ experiments indicated the
      alloploid nature of H. depressum. Both sequences allow H. chilense chromatin to
      be distinguished from wheat chromosomes in tritordeum.

PMID- 8537000
TI  - C-banding plus fluorochrome staining shows differences in C-, G-, and R-bands in
      human and mouse metaphase chromosomes.
AB  - C-banded slides stained with DAPI or chromomycin A3 show different banding
      patterns between human and L929 mouse cell line metaphase chromosomes, which are
      also different from those obtained with standard Giemsa C-banding or fluorochrome
      staining. Human metaphase chromosomes pretreated for C-banding and stained with
      DAPI show simultaneous C- and DA-DAPI banding patterns, whilst the mouse
      metaphase chromosomes show both C-banding and G/Q banding like patterns. However,
      the chromomycin A3 staining of pre-C-banded metaphase chromosomes reveals
      conspicuous R-banding in man that is absent in mouse. Chromatin species-specific
      structural factors would explain these results, which prevent simple comparisons
      of R-, G-, and C-bands among different organisms. The markers induced by this
      technique may be of practical use for chromosome identification in human-mouse
      somatic cell hybridization cultures.

PMID- 8537001
TI  - Variation of nitrate reductase genes in selected grass species.
AB  - In order to study the variation of nitrate reductase (NR) genes among grass
      species, gene number, intron size and number, and the heme-hinge fragment
      sequence of 25 grass species were compared. Genomic DNA cut with six restriction
      enzymes and hybridized with the barley NAD(P)H and NADH NR gene probes revealed a
      single NAD(P)H NR gene copy and two or more NADH NR gene copies per haploid
      genome in most of the species examined. Major exceptions were Hordeum vulgare, H.
      vulgare ssp. spontaneum, and Avena strigosa, which appeared to have a single NADH
      NR gene copy. The NADH NR gene intron number and lengths were examined by
      polymerase chain reaction amplification. Introns I and III appeared to be absent
      in at least one of the NADH NR genes in the grass species, while intron II varied
      from 0.8 to 2.4 kilobases in length. The NADH NR gene heme-hinge regions were
      amplified and sequenced. The estimated average overall nucleotide substitution
      rate in the sequenced region was 7.8 x 10(-10) substitutions/site per year. The
      synonymous substitution rate was 2.11 x 10(-9) substitutions/synonymous site per
      year and the nonsynonymous substitution rate was 4.10 x 10(-10)
      substitutions/nonsynonymous site per year. Phylogenetic analyses showed that all
      of the wild Hordeum species examined clustered in a group separate from H.
      vulgare and H. vulgare ssp. spontaneum.

PMID- 8537002
TI  - Analysis of genetic diversity in a sweetpotato (Ipomoea batatas) germplasm
      collection using DNA amplification fingerprinting.
AB  - A DNA amplification fingerprinting (DAF) approach was employed to develop
      individual-specific profiles and analyze genetic relationships among 73 plant
      introductions of sweetpotato (Ipomoea batatas (L.) Lam.) including unadapted
      lines from around the world and a few selected U.S.A. cultivars. Reliable and
      informative fingerprint profiles were obtained employing single octamer primers
      and Stoffel fragment Taq polymerase in the polymerase chain reaction,
      polyacrylamide-based vinyl polymer for electrophoresis, and silver staining to
      visualize the DNA. Using seven highly informative octamer primers, individual
      specific DAF profiles were obtained for all accessions tested. The degree of
      polymorphism in the sweetpotato collection was very large, indicating a high
      level of genetic variability. Several accessions clustered together based on
      their geographic source. Most U.S.A. cultivars formed a separate cluster in the
      phenogram, while accessions from Papua New Guinea exhibited the highest genetic
      diversity. The wild species I. triloba and tetraploid I. batatas formed a group
      distinct from the cultivated sweetpotato. DAF appears to be useful in sweetpotato
      germplasm characterization and may be employed to identify duplicate accessions
      or for creation of core subsets. DAF data may also be useful for facilitating the
      selection of parents for a breeding program to ensure a broad genetic base.

PMID- 8537003
TI  - Detection of maize DNA sequences amplified in wheat.
AB  - Genomic in situ hybridization to somatic metaphase chromosomes of hexaploid wheat
      cv. Chinese Spring using biotinylated maize genomic DNA as a probe revealed the
      existence of amplified maize DNA sequences in five pairs of chromosomes. The in
      situ hybridization sites were located on chromosomes 1A, 7A, 2B, 3B, and 7B. One
      pair of in situ hybridization sites was also observed in hexaploid oat. The
      locations and sizes of in situ hybridization sites varied among progenitor
      species.

PMID- 8537004
TI  - Variability in wheat based on low-copy DNA sequence comparisons.
AB  - The chromosomes of the B genome of hexaploid wheat (AABBDD) do not pair
      completely with those of any of the diploid species with genomes similar to B.
      Various biochemical and molecular analyses have suggested that each of the five
      diploid species in section Sitopsis of Triticum are ancestral to B. These
      observations have led to the hypothesis that the B genome may be polyphyletic,
      descending from more than one diploid ancestor. This hypothesis may account for
      differences between the wheat B genome and the diploids and also for variability
      that currently exists among different wheat accessions. In this study, we cloned
      and compared nucleotide sequences for three low-copy DNA fragments from the B and
      D genomes of several wheat accessions and from diploid relatives of the B and D
      genomes. Our results suggested that the amount of DNA sequence variability in
      wheat is low, although somewhat more variability existed in the B genome than in
      the D genome. The B genome of wheat was significantly diverged from all the
      Sitopsis diploid species, and Triticum speltoides was closer to B than to other
      members of this section. The D genome of wheat was very similar to that of its
      progenitor, Triticum tauschii. No evidence for a polyphyletic origin of the B
      genome was found. A more parsimonious hypothesis is that the wheat B genome
      diverged from its diploid ancestor after the original hybridization event
      occurred.

PMID- 8537005
TI  - The occurrence of a mutant dimerizable histone H5 in Japanese quail erythrocytes.
AB  - An allelic variant of linker histone H5 has been found in the erythrocytes of
      Japanese quail (Coturnix japonica) descended from a small group of feral birds
      captured on the island of Hawaii. This variant spontaneously forms protein dimers
      in vitro in the absence of reducing agents. That this depends upon the
      introduction of a sulfhydryl group (presumably because of a cysteine
      substitution) is indicated by its reaction with 2-nitro-5-thiocyanobenzoate and
      by its fluorescence after reaction with 4-aminosulfonyl-7-fluoro-2,1,3
      benzoxadiazole. This is the first reported example of cysteine in a vertebrate
      linker histone and offers a specific reactive site for structural studies. A
      homozygous line for this form of H5 is being developed.

PMID- 8537006
TI  - Mapping of digested and undigested random amplified microsatellite polymorphisms
      in barley.
AB  - The broad use of microsatellites as a tool for constructing linkage maps in
      plants has been limited by the need for sequence data to detect the underlying
      simple sequence repeats. Therefore, random amplified microsatellite polymorphisms
      (RAMPs) were studied as an alternative approach for barely mapping. Labelled
      (GA)n simple sequence repeat primers were combined with RAPD primers of different
      length and sequence to generate RAMPs. To get additional polymorphisms (called
      dRAMPs), the obtained products were also analysed after digestion with MseI.
      There were 0-11 polymorphisms found per primer combination. Sixty RAMPs/dRAMPs
      identifying 40 new loci were mapped onto a barley RFLP map. The new DNA markers
      are found on all chromosomes and they increased the length of the barely map by
      174 cM to a total of 1270 cM. Interestingly, the RAMPs/dRAMPs caused stretching
      effects in genome areas where stretching was also observed for AFLPs.

PMID- 8537007
TI  - Are anthropometric changes in healthy adults caused by modifications in dietary
      habits or by aging?
AB  - The aim of this work was to investigate to what extent age-dependent
      anthropometric changes are causally related to changes in dietary habits. In a
      randomly obtained sample of 246 healthy adults in the age range of 20-90 years
      from a well-defined agrarian population, the intake of proteins, fat and
      carbohydrates in males decreases with age (r = -0.65, p < 0.001; r = -0.65, p <
      0.001; r = -0.5, p < 0.01, respectively), but in females it remains unaltered
      (e.g. the mean +/- SD daily protein intake in young adult females is 74 +/- 31
      vs. 71 +/- 11 g in individuals over 80); in males it decreases from 140 +/- 34 to
      71 +/- 13 g. On the contrary, in both sexes the muscle-mass-related measurements
      decrease (r = -0.45, p < 0.001; vs. r = -0.41, p < 0.001; mean values of the
      quotient lean body mass with body length in young adult females and males were
      41.9 +/- 4.4 and 52.7 +/- 5.9 vs. 35.0 +/- 3.1 and 43.2 +/- 5.0, respectively, in
      individuals over 80, p < 0.001 in both sexes). From 35 onwards, the daily urea
      excretion-as a marker of the protein degradation rate-declines significantly with
      age, but without a clear correlation to the protein intake (r = 0.38), as occurs
      during young adulthood (r = 0.63). Furthermore, body fat content tends to
      increase with age, but the differences are statistically significant only in
      males of very advanced age (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537008
TI  - Influence of age, treadmill running, and food restriction on plasma fibrinogen
      concentration and expression of gamma chain mRNA in female Sprague-Dawley rats.
AB  - Plasma fibrinogen concentration and expression of mRNA encoding the gamma-chain
      of fibrinogen were determined in female Sprague-Dawley rats aged 10, 21 and 30
      months. Both parameters increased significantly with age in a parallel fashion.
      Food restriction was able to reduce the age-dependent increase of both plasma
      concentration and gene expression to levels below young controls. On the other
      hand, long-term treadmill running failed to influence the plasma fibrinogen
      concentration. From these results we conclude that the plasma fibrinogen
      concentration increases with age due to an increased fibrinogen biosynthesis.

PMID- 8537009
TI  - Plasma lipid, apolipoprotein and Lp(a) levels in elderly normolipidemic women:
      relationships with coronary heart disease and longevity.
AB  - The relation between plasma lipids and coronary heart disease (CHD) in the
      elderly is still debated, as well as the proposed role of lipoproteins as markers
      of longevity. In this study both normolipidemic elderly and middle-aged women
      with CHD showed higher triglycerides and apolipoprotein B levels and lower high
      density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels in comparison
      with age-matched subjects without CHD. In the middle-aged group, hypertension and
      HDL-cholesterol levels and, in the elderly group, only HDL-cholesterol levels
      were independently associated with CHD. No significant difference was found
      between a group of healthy centenarians and elderly and middle-aged subjects
      without CHD. These data suggest that plasma lipids are also related to CHD in the
      elderly and that, even if at present we are not able to consider them as
      predictors of longevity, some lipoprotein features may contribute to select
      subgroups of subjects in which other factors play a further role in life
      expectancy.

PMID- 8537010
TI  - Two-point discrimination test of the skin as an index of sensory aging.
AB  - Although the two-point discrimination test of the skin is a simple test of the
      sensory nerve function, there have been few studies on age-related changes in the
      ability to discriminate between two points in a large noninstitutionalized
      population. In this study we attempted (1) to determine normal values on the two
      point discrimination test by age and gender in a large population with a wide age
      span; (2) to describe age-related changes on the two-point discrimination test;
      and (3) to test the independence of this index from other indices measuring
      physiological aging by sensory functions, such as accommodation and hearing
      tests. The subjects were 2,036 men and women aged 10-87 years. The minimal
      distance at which two points could be discriminated was measured longitudinally
      on a line from the palmar pad to the base of the index finger of the right hand.
      The two points of a caliper were applied at the same time (stationary two-point
      discrimination test) using the weight of the caliper alone. An age-related
      decline in the ability to discriminate two points was apparent, but there were no
      significant differences in ability between men and women. The minimal distance of
      discrimination on the hand increased almost linearly between 10 and 60 years of
      age. The results of the two-point discrimination test of the skin were
      independent of those of visual accommodation tests and hearing loss of high
      frequency sound. From these results, the two-point discrimination test of the
      skin can be used as a powerful and simple index of sensory aging.

PMID- 8537011
TI  - Site-specific relative risk of fractures in the institutionalized elderly.
AB  - A 3-year prospective study was performed to evaluate the incidence of fractures
      in institutionalized elderly and associated risk factors. A total of 197 subjects
      (47 males and 150 females, mean age 81.5 +/- 8.0 years) were included in the
      study. The annual fracture incidence was 7.8%. All hip fractures occurred in
      female subjects (annual incidence = 3.7%). As expected, the incidence of
      fractures is higher in walking subjects. In walking subjects (n = 128) logistic
      regression analysis showed falls [adjusted relative risk (RR) = 3.3; 95%
      confidence interval (CI) = 1.3-8.4] and age (adjusted RR = 1.7; 95% CI = 1.1-2.3)
      to be variables independently and significantly associated with fractures, after
      adjusting for baseline bone mineral density (BMD) and sex. Hip fractures were
      associated with age (RR = 1.6; 95% CI = 1.1-2.3), and non-hip fractures with
      falls (RR = 4.1; 95% CI = 1.3-13.4). The importance of low BMD as a risk factor
      for fractures is reduced in the institutionalized elderly. However, other
      fracture-site-specific risk factors exert a greater influence.

PMID- 8537012
TI  - Prevalence of low vision in elderly patients admitted to an acute geriatric unit
      in Liverpool: elderly people who fall are more likely to have low vision.
AB  - The prevalence of visual impairment among elderly patients admitted to hospital
      is unknown. This group of patients may be particularly at risk from poor vision
      which could jeopardise their independence. A prospective study of visual
      imapairment and its aetiology in acute geriatric admissions assessed after the
      acute illness had settled was performed. Subjects were all patients aged 65 years
      or over, excluding those chronically confused, admitted to the Department of
      Geriatric Medicine at the Royal Liverpool University Hospital with an acute
      medical illness. After the acute illness had settled visual impairment, as
      defined by the American criteria (best acuity 6/18), was assessed on the ward
      with a Snellen chart read at 6 m using binocular vision and current glasses.
      Those patients identified with impaired vision on initial screening were formally
      assessed in the ophthalmology department to identify the cause. 200 patients were
      examined. 101 patients (50.5%) had impaired vision. In these patients,
      correctable refractive errors were present in 40%, cataract in 37% and senile
      macular degeneration in 14%. Of the 101 patients with impaired vision 79% had a
      reversible cause. Comparing these results with a recent study in the community
      showed a much higher incidence for patients admitted to hospital. There was a
      particularly high prevalence in those elderly patients who were admitted with
      falls (76%, p = 0.0003). In conclusion, elderly patients, especially those
      presenting with falls, admitted to hospital have a high prevalence of visual
      impairment. Visual impairment may be compounding or causing falls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8537013
TI  - Health-related quality of life and dizziness in old age.
AB  - In a representative population of ambulant and home-dwelling 76-year-old citizens
      in Sweden (n = 565), dizziness was reported in about one third of the sample and
      more frequent in women. The dizzy subjects had more locomotor disorders, angina,
      urinary incontinence, stroke/paresis, and mental disorders than the non-dizzy.
      Unsteadiness was the most frequently reported sensation of dizziness and was more
      common in women than in men. Dizziness had a detrimental influence on all quality
      of life dimensions and daily life areas, as measured by the Nottingham Health
      Profile (NHP), except home life and, in women, social life. Dizzy subjects
      reported more frequently memory problems and anxiety than non-dizzy subjects.
      Dizziness showed a significant correlation with nervousness and depression in
      men. Dizziness seems to be one of the most important single symptoms with a
      negative influence on well-being in old age. It should be recognized as a serious
      complaint, especially in men, and, therefore, recorded in regular screenings in
      the elderly.

PMID- 8537014
TI  - Differential involvement of phospholipase C isozymes in Alzheimer's disease.
AB  - Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal
      transduction. We demonstrated that an antibody to an isozyme of PLC, PLC-delta 1,
      produced intense staining of neurofibrillary tangles (NFT) in the brains of
      patients with Alzheimer's disease (AD). Western blot analysis using a specific
      antibody for PLC-delta 1 showed that the concentration of PLC-delta 1 protein was
      significantly higher in the cytosolic fraction of AD cortical tissues than in
      controls. The activity of PLC-delta 1, which hydrolyzes phosphatidylinositol, was
      not significantly different in the Alzheimer and control cytosolic fraction,
      indicating that the specific activity of PLC-delta 1 is decreased in Alzheimer
      brains. Western blot analysis also showed that the concentration of PLC-delta 1
      and PLC-gamma 1 was significantly lower in the membraneous fraction of AD
      cortical tissues than in controls. These results suggest a differential
      involvement of PLC isozymes in AD.

PMID- 8537015
TI  - Application of long-term cultured neurons in aging and neurological research:
      aluminum neurotoxicity, synaptic degeneration and Alzheimer's disease.
AB  - Dissociated hippocampal and cerebral cortical neurons from rat embryonic brain
      form many synapses in culture. The neuronal networks in culture fire
      spontaneously in synchronous oscillation and can be maintained for long periods
      of up to 6 months. To establish the relevance of this long-term culture to aging
      and neurodegenerative diseases, effects of long-term exposure to aluminum, a risk
      factor for Alzheimer's disease, on the cultured cortical neurons were
      investigated. It appeared that aluminium promoted the aggregation of amyloid beta
      protein and enhanced its neurotoxicity.

PMID- 8537016
TI  - Decreased mitogenic and osteogenic responsiveness of calvarial osteoblasts
      isolated from aged rats to basic fibroblast growth factor.
AB  - Osteoporosis seen in aged individuals is represented by the reduced bone mass
      most likely resulting from decreased bone formation by osteoblasts. To examine
      whether aging causes a decrease in osteoblast activity, calvarial osteoblasts
      were isolated from aged rats (AOB) and studied for the capacity of the cells to
      form mineralized bone-like nodules in comparison with that of fetal calvarial
      osteoblasts (FOB). There were no significant differences in basal mineralized
      bone-like nodule formation determined by quantifying the size of the nodules
      which were formed in the cultures of AOB and FOB. However, the responsiveness of
      AOB to growth factors was profoundly reduced. AOB showed only marginal increase
      in mineralized bone-like nodule formation and growth in response to basic
      fibroblast growth factor (bFGF). On the other hand, bFGF markedly promoted
      mineralized bone-like nodule formation and proliferation in FOB. These results
      suggest that decreased responsiveness to local osteotropic growth factors such as
      bFGF might account for the reduced bone formation by aged osteoblasts, which in
      turn leads to the loss of bone mass characteristic for senile osteoporosis.

PMID- 8537017
TI  - Significance of defective endothelial signal transduction in impaired endothelium
      dependent relaxation in atherosclerosis.
AB  - The significance of the defective endothelial signal transduction in the impaired
      endothelium-dependent relaxations in atherosclerosis and related conditions was
      examined. Pertussis toxin-sensitive endothelium-dependent relaxations were
      prominently impaired in experimental atherosclerosis in pigs. The expression of
      endothelial Gi protein was reduced in atherosclerosis and related conditions in
      human coronary arteries. Thus, the dysfunction of pertussis toxin-sensitive G
      protein (Gi protein) may contribute to the impairment of the endothelium
      dependent relaxations in atherosclerosis.

PMID- 8537018
TI  - Developmental regulation of Xenopus beta-amyloid precursor protein gene
      expression.
AB  - We isolated cDNA clones from Xenopus larvae, which encode a protein highly
      homologous to the mammalian beta-amyloid precursor protein (APP), and analyzed
      developmental change of Xenopus APP gene expression. The maternal APP mRNA is
      accumulated from early oogenesis, but after fertilization, this mRNA is degraded
      reaching a minimum level around the gastrula stage. Zygotic transcription appears
      to start after the gastrula stage and to continue during subsequent embryonic and
      larval stages. These results suggest some fundamental roles of the APP molecule
      in Xenopus early development.

PMID- 8537020
TI  - Multinational clinical and pathologic registry of retinoblastoma. Retinoblastoma
      International Collaborative Study report 2.
AB  - BACKGROUND: The Retinoblastoma International Collaborative Study is a
      multinational prospective clinical and pathologic registry designed to collect
      baseline clinical information, data on methods of treatment, and information on
      the subsequent clinical course of children with retinoblastoma. METHODS: 206
      children with newly diagnosed retinoblastoma were evaluated in the participating
      clinical centers between 1 July 1987 and 31 December 1989. All of the children
      underwent comprehensive baseline assessment of multiple clinical variables
      prospectively according to a standard protocol. The recorded values were
      tabulated and analyzed. RESULTS: The 206 children with retinoblastoma included 99
      boys (48.1%) and 107 girls (51.9%). The mean age at diagnosis was 21.2 mo in the
      total study group. One hundred twenty-seven of the 206 children (61.7%) had
      unilateral disease, while 79 (38.3%) had bilateral involvement. The mean age at
      diagnosis in the bilateral cases (14.6 mo) was substantially less than in the
      unilateral ones (23.5 mo). The great majority of patients (approximately 75%) had
      advanced disease (group V in both Reese-Ellsworth and Essen prognosis
      classifications) in the affected eye (unilateral cases) or the more severely
      affected eye (bilateral cases). CONCLUSIONS: This study shows that there is a
      dedicated group of international ophthalmologists and other physicians who are
      willing to participate in multicenter cooperative clinical studies of
      retinoblastoma and that a relatively large group of children with this ocular
      malignancy can be enrolled within this framework during a reasonably short time
      for the purposes of future studies.

PMID- 8537019
TI  - The development of pars plana vitrectomy: a personal account.

PMID- 8537021
TI  - Prevalence of HTLV-I-associated uveitis in the Kanto Plain, Japan.
AB  - BACKGROUND: Seroprevalence of antibody to human T-lymphotropic virus type I (HTLV
      I) is high in the island of Kyushu, Japan. Reports on the etiological analysis of
      HTLV-I in patients with uveitis primarily document cases in this island. We
      studied the seroprevalence of HTLV-I at the Department of Ophthalmology in
      Yokohama City University Hospital and in Odawara Municipal Hospital, which are in
      the Kanto Plain on the island of Honshu, Japan. METHODS: The subjects were 741
      patients who visited the two hospitals. The presence of serum antibodies against
      HTLV-I was assessed using the method of particle agglutination. RESULTS: Of 454
      patients with nonuveitic ocular diseases, 9 (1.98%) were seropositive. Of 143
      patients with definite diagnosis of uveitis, 1 (0.70%) was seropositive. Of 144
      patients with non-specific uveitis (etiology undefined), 8 (5.56%) were
      seropositive. Thus, the prevalence of serum antibodies to HTLV-I was higher in
      patients with non-specific uveitis than in patients with specific uveitis or
      nonuveitic ocular diseases. Common ocular symptoms of 8 HTLV-I-infected patients
      with non-specific uveitis were compatible with the clinical features of uveitis
      described as HTLV-I-associated uveitis (HAU). CONCLUSION: It is important to
      suspect HAU in patients with uveitis of unknown etiology, even outside known
      areas of prevalence.

PMID- 8537022
TI  - Increased release of tenascin in tear fluid after photorefractive keratectomy.
AB  - BACKGROUND: Extracellular matrix protein tenascin (TN) is expressed in the
      anterior stroma during corneal wound healing. In this study we analysed TN
      release in tear fluid after photorefractive keratectomy (PRK). METHODS: Tear
      fluid TN concentrations of ten PRK patients were measured with an immunoassay.
      Tear fluids were collected preoperatively and 1, 2 and 7 days after PRK. The tear
      fluid collection time and the volume of tears collected were registered. Because
      tear fluid flow was greatly increased postoperatively, tear fluid flow-corrected
      release (TN flux) was calculated. RESULTS: The tear fluid flow was 4.50 +/- 0.94
      microliters/min (mean +/- SEM) preoperatively, 55.48 +/- 16.70 microliters/min (P
      < 0.01) on the 1st, 33.91 +/- 7.91 microliters/min (P < 0.01) on the 2nd, and
      13.79 +/- 5.49 microliters/min (P > 0.05) on the 7th postoperative day. The
      preoperative TN concentration was 0.85 +/- 0.20 microgram/ml. On the 1st
      postoperative day it decreased to 0.37 +/- 0.17 microgram/ml (P > 0.05), most
      likely due to the dilution effect caused by hypersecretion after PRK. The TN
      concentration was 0.67 +/- 0.12 microgram/ml (P > 0.05) on the 2nd and 0.78 +/-
      0.15 micrograms/ml (P > 0.05) on the 7th postoperative day. The preoperative TN
      flux was 5.23 +/- 1.88 ng/min. On the 1st and 2nd postoperative days the TN flux
      was 14.40 +/- 4.99 ng/min (P < 0.05) and 22.66 +/- 6.12 ng/min (P < 0.05),
      respectively. On the 7th postoperative day a tendency towards decreased flux
      (14.00 +/- 6.02 ng/min, P > 0.05) was observed. CONCLUSION: Although there is a
      minor decrease in TN concentration after PRK due to increased tear fluid flow, a
      significant increase in TN flux was observed. Complete reepithelialization of the
      ablated area was observed in all eyes at the follow-up visit on postoperative day
      7.

PMID- 8537023
TI  - Endothelin-1 plasma levels in normal-tension glaucoma: abnormal response to
      postural changes.
AB  - BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by
      vascular endothelial cells. ET-1 may have a role in the pathogenesis of various
      vascular diseases. There are reports in the literature that ET-1 plasma levels
      are raised in normal-tension glaucoma (NTG) patients. METHODS: ET-1
      concentration, plasma renin activity, and 24-h blood pressure were measured in 21
      high-tension glaucoma (HTG) patients, 19 NTG patients, and 20 non-glaucomatous
      controls in supine and upright positions. RESULTS: ET-1 plasma levels tended to
      be higher in NTG patients (3.2 +/- 2.2 pg/ml) than in HTG patients (2.2 +/- 0.6
      pg/ml) and controls (2.6 +/- 0.7 pg/ml). The differences, however, were not
      statistically significant. The individual scatter was significantly greater in
      the NTG group, indicating that our NTG patients are a heterogeneous population.
      The physiological increase in ET-1 plasma level after changing from the supine to
      the upright position was absent in NTG patients. Plasma renin activities tended
      to be lower in NTG patients (1.2 +/- 1.2 ng/ml/h) than in HTG patients (1.3 +/-
      0.8 ng/ml/h) and controls (2.0 +/- 1.7 ng/ml/h). This may explain why NTG
      patients had relatively low blood pressure despite high ET-1 levels. CONCLUSIONS:
      Our data support the hypothesis that vascular dysfunction may be involved in the
      pathogenesis of optic nerve damage in normal-tension glaucoma.

PMID- 8537024
TI  - Diode laser photocoagulation for stage 3+ retinopathy of prematurity.
AB  - BACKGROUND: Laser photocoagulation in retinopathy of prematurity (ROP) appears to
      have fewer adverse effects than cryotherapy and seems to be at least as
      effective. METHODS: To evaluate the efficacy and safety of diode laser
      photocoagulation, we included 42 eyes with stage 3+ ROP of 24 preterm infants
      (gestational age 24-29 weeks, mean +/- SD 26.6 +/- 1.3 weeks; birth weight 480
      1400 g, 896 +/- 196 g) in a prospective clinical study. Photocoagulation
      treatment was performed using a diode laser (810 nm) with a laser indirect
      ophthalmoscope delivery system. Follow-up ranged from 3 to 16 months (8.8 +/- 4.0
      months). RESULTS: In 39 (93%) of 42 eyes ROP regressed after a single laser
      treatment and the outcome was a flat, attached retina. One eye (2%) had a second
      laser session and another eye (2%) had additional retinal detachment surgery,
      resulting in the regression of ROP and a flat, attached retina. Thus, the success
      rate was 41 (98%) out of 42 eyes. In one (2%) of the 42 eyes treatment failed and
      ROP progressed to stage 5, although additional retinal detachment surgery was
      performed. No adverse side effects of diode laser treatment were noticed except
      for a small amount of retinal/preretinal bleeding in the ridge in five eyes (12%)
      and a small postoperative anterior chamber hemorrhage in one eye (2%) with dense
      tunica vasculosa lentis. Neither lenticular opacities nor cataract formation were
      encountered. CONCLUSION: Diode laser photocoagulation for stage 3+ ROP showed
      only minor side effects and was at least as effective as cryotherapy treatment.

PMID- 8537025
TI  - Self-assessment of angles of strabismus with photographic Purkinje I and IV
      reflection pattern evaluation.
AB  - BACKGROUND: Accurate assessment of the angle of strabismus, e.g. of variable
      angles of strabismus, is crucial in preoperative patient management and is
      usually performed in a clinical environment. Objective assessment by patients
      themselves, under everyday conditions, could contribute to a better preoperative
      work-up. A new objective evaluation procedure for the measurement of manifest
      angles of strabismus for near and distance fixation by the patient himself is
      presented. METHODS: To account for the modified experimental setup used for the
      self-assessment, an amended computation procedure of Purkinje reflection pattern
      evaluation was developed. For measurement, patients and controls placed their
      head on a head/chin rest and fixated at 33 cm or 4 m distance in primary
      position. A reflex camera and three photo flash units were positioned on a
      special frame underneath the visual axis and in front of the subject so that both
      eyes could be photographed simultaneously. The camera's remote shutter control
      was released together with the photo flash units by the properly fixating
      subject. The angles of strabismus were obtained from the series of pictures
      through later evaluation of the Purkinje I and IV reflection patterns recorded in
      the photographs of the eyes. RESULTS: Measurements of the ocular alignment in two
      control groups and in a group of strabismic subjects showed satisfactory accuracy
      of the "self-assessment" method compared to "standard" Purkinje reflection
      pattern evaluation and orthoptic measurements of the angle of strabismus.
      CONCLUSION: The modified "self-assessment" method can be used for the objective
      recording of angles of strabismus as needed in the preoperative work-up of
      patients with variable angles of strabismus, over prolonged periods of time, and
      outside a clinical setting.

PMID- 8537026
TI  - The effect of topical cholinergic medications on human Tenon's capsule
      fibroblasts in tissue culture.
AB  - BACKGROUND: The prior long-term use of topical anti-glaucoma medications has been
      suggested as an adverse factor for the outcome of trabeculectomy. The mechanism
      of action is not known. This study investigates the effect of cholinergic
      medications on the proliferation and viability of human Tenon's capsule
      fibroblasts in tissue culture to see whether this may be one mechanism by which
      increased surgical failure occurs. METHODS: We examined the effect of two
      commercial pilocarpine products, pure pilocarpine hydrochloride, and pure
      benzalkonium chloride, at various dilutions, on the proliferation (as assessed by
      3H-thymidine uptake) and viability (assessed microscopically) of human Tenon's
      capsule fibroblasts in tissue culture. RESULTS: None of the tested compounds
      stimulated the proliferation of fibroblasts in tissue culture. Three of the
      compounds inhibited proliferation, and all compounds had toxic effects on cell
      morphology. At equivalent dilutions of commercially available concentration, pure
      benzalkonium chloride and the commercial product containing it appeared more
      toxic and antiproliferative to cells in culture than pure pilocarpine
      hydrochloride and the preservative-free commercial product. CONCLUSIONS: These
      results show an antiproliferative and toxic effect of medications on fibroblasts
      in tissue culture. They do not support the theory that topical medications
      directly stimulate fibroblast proliferation. The possible relevance of these
      results for the outcome of glaucoma surgery is discussed.

PMID- 8537028
TI  - Optic nerve head analyzer and Heidelberg retina tomograph: relative error and
      reproducibility of topographic measurements in a model eye with simulated
      cataract.
AB  - BACKGROUND: We measured the relative error and reproducibility of the optic nerve
      head analyzer (ONHA) and the Heidelberg retina tomograph (HRT) in a model eye
      with a cataract that was simulated by Bangerter foils. METHODS: There were two
      artificial discs and one retinal elevation (the latter could not be analyzed by
      the ONHA) that could be inserted into the model eye. The relative error of the
      parameter 'cup area' ('cup volume') of the ONHA for the measurement of artificial
      disc no. 1 changed from 1.1% (5.4%) without Bangerter foil to 7.9% (7.6%) with
      Bangerter foil 0.6. The standard deviation of the ONHA increased from 0.059 mm2
      (0.1 mm3) without Bangerter foil to 0.142 mm2 (0.121 mm3) with Bangerter foil
      0.6. With the smaller artificial disc no. 2, no measurements with Bangerter foils
      were obtained. RESULTS: Relative error and reproducibility of the parameter
      'volume below (above) surface' of the HRT did not show any consistent change with
      increasing intensity of the simulated cataract. With artificial disc no. 1, the
      relative error without Bangerter foil was 14.6%, while the worst relative error
      with one of the Bangerter foils 0.8 to 0.4 was 16.4%. The corresponding values
      for the standard deviation were 0.019 mm3 and 0.033 mm3. With the smaller
      artificial disc no. 2, the relative error without Bangerter foil was 6.3%, while
      the worst relative error with one of the Bangerter foils 0.8 to 0.2 was 18.3%.
      The corresponding values for the standard deviation were 0.016 mm3 and 0.017 mm3.
      The relative error in measuring a retinal elevation without a Bangerter foil was
      2.3%, with a Bangerter foil 11.2-18.0%. The standard deviation was 0.068 mm3
      without Bangerter foil and 0.013-0.023 mm3 with Bangerter foils. CONCLUSION: Our
      data support the assumption that the HRT is able to measure fundus structures
      even in the case of opaque optical media. The HRT is superior to the ONHA in this
      regard.

PMID- 8537027
TI  - Tissue expression of lipocalins in human lacrimal and von Ebner's glands:
      colocalization with lysozyme.
AB  - BACKGROUND: Tear-specific prealbumin is a group of proteins recently renamed as
      the tear lipocalins. These proteins were initially described as unique to
      lacrimal fluid. The tissue distribution and localization have never been
      thoroughly studied. METHODS: The distribution of purified tear lipocalins was
      studied in many human secretions and tissues by western blots,
      immunohistochemistry and immunoelectron microscopy. RESULTS: Tear lipocalin
      species of the same molecular weights were observed in western blot lanes loaded
      with tears, saliva, and protein extracts from the lacrimal and lingual von
      Ebner's glands. Lacrimal and von Ebner's glands contained tear lipocalins; other
      human tissues and secretions, including other salivary glands and taste buds, did
      not. Tear lipocalins colocalized with lysozyme in serous acinar cells of lacrimal
      and von Ebner's glands. Ultrastructurally, tear lipocalins were present on
      polyribosomes, endoplasmic reticulum, and Golgi areas. Lipocalins were
      concentrated in lacrimal secretory granules in amounts commensurate with a
      regulated pathway. CONCLUSION: Tear lipocalins are expressed and truncated
      similarly in lingual von Ebner's and lacrimal glands, but not at all in other
      human tissues. Lipocalins are expressed and secreted with lysozyme. Lipocalins
      are concentrated in secretory granules in an amount consistent with a regulated
      secretory pathway.

PMID- 8537029
TI  - The effect of nasolacrimal occlusion on drug-induced mydriasis.
AB  - BACKGROUND: Nasolacrimal occlusion has been shown to improve the efficacy of some
      topically applied ocular drugs. The aim of this study was to investigate the
      effect of nasolacrimal occlusion on tropicamide-induced mydriasis. METHODS: We
      compared pupillary dilatation by 0.125% tropicamide with and without nasolacrimal
      occlusion in 40 healthy volunteers. RESULTS: Analysis of variance with repeated
      measures failed to show any advantage due to nasolacrimal occlusion in drug
      induced mydriasis. CONCLUSION: Nasolacrimal occlusion did not increase the
      mydriasis obtained with 0.125% tropicamide.

PMID- 8537031
TI  - Improvements of Littmann's theoretical method.

PMID- 8537030
TI  - Efficacy of topical gentamicin treatment after 193-nm photorefractive keratectomy
      in an experimental Pseudomonas keratitis model.
AB  - BACKGROUND: The treatment of Pseudomonas keratitis has many limitations, and
      further investigation to identify more effective approaches is required. We
      therefore studied the possible contribution of the debridement effect of 193-nm
      excimer laser on Pseudomonas keratitis in rabbit eyes. METHODS: Pseudomonas
      keratitis was induced in 30 rabbit eyes by inflicting controlled central corneal
      scratches and applying a drop of Pseudomonas aeruginosa suspension. After 24 h,
      one cornea of each animal was photo-ablated (excimer laser: fluency 90 mJ/cm2, 10
      Hz, 213 pulses), yielding 50 microns of tissue ablation, while the follow cornea
      served as control. Five groups of six animals each were formed and received: a
      subconjunctival injection of gentamicin 20 mg (group 1), topical 14 mg/ml
      gentamicin hourly (group 2) or every 2.5 h (group 3), or NaCl 0.9% hourly (group
      4) for 8 h. In group 5, animals were sacrificed without additional treatment.
      After 9 h corneas were excised, homogenized, serially diluted, and plated on agar
      blood plates. The numbers of colony-forming units (CFU) per cornea were
      statistically evaluated (Mann-Whitney test). RESULTS: In control eyes, a greater
      decrease of CFU was observed in group 2 than in group 3 (P = 0.03). In laser
      ablated eyes, there was no difference in CFU between groups 2 and 3. Comparison
      of the excimer-treated and control eyes revealed a greater number of bacteria
      (CFU) in controls only in group 3 (P = 0.02). CONCLUSION: Our study suggests that
      controlled debridement of cornea with excimer laser may improve the effect of
      topical antibiotics.

PMID- 8537032
TI  - [Radiotherapy in vulvar cancer. Experience in the Hospital de Oncologia, CMN,
      SXXI, IMSS].
AB  - Between 1986 and 1992, 42 patients with carcinoma of the vulva diagnosis, were
      treated at the Hospital de Oncologia, CMN, SXXI. Mean age was 63 years. There was
      1 case stage I, 5 stage II, 25 stage III, 4 stage IV, 2 with recurrent disease
      and 5 patients could not be classified. Local control was reached in 60% of
      patients however, 12 patients developed local recurrence after surgery and/or
      radiation therapy, finally 43% of patients remained disease free after a mean of
      19 months of followup. In the subset of advanced disease patients treated with
      radical or preoperative radiation therapy (27 patients), 41% of them remained
      without disease. Mean radiation doses for patients treated only with radiation
      therapy was 6500 cGy. Late vulvar fibrosis and acute desquamative dermatitis,
      were the morbidity more frequently observed. New directions in the management of
      vulvar cancer must be developed to improve treatment results, in patients with
      advanced disease.

PMID- 8537033
TI  - [HELLP syndrome as manifestation of pre-eclampsia decompensation during
      puerperium. 2 case reports].
AB  - Two extreme cases of pregnancy-induced hypertension with puerperal HELLP syndrome
      are presented and the literature is review. HELLP is an English acronym, for
      describing the preeclamptic or eclamptic patient, who also has hemolysis,
      elevated hepatic enzymes and low platelets. Its etiology has not been elucidated,
      but it has been accepted the theory of dysequilibrium in prostanoid metabolism.
      It has an incidence of 5 to 15% among patients with pregnancy-induced
      hypertension. Maternal mortality is about 10 to 28% and neonatal of 40%. Owing to
      fatal complications, treatment consist of interrupting pregnancy. Point out the
      importance of early detection of this clinic entity, which improves maternal
      fetal prognosis.

PMID- 8537034
TI  - [Maternal mortality in the Hospital Central Militar. Report on 25 years: 1968
      1991].
AB  - A total of 122 cases of maternal death are reported. These cases occurred at the
      Hospital Central Militar, a 3rd. level general hospital, during the period of 25
      years from 1968 to 1992. Maternal mortality rate was 181.7 x 100,000 live births
      (143.0 when non-obstetrical deaths were eliminated according to the World Health
      Organization recommendation). Annual and quinquennial variations were very width
      and erratic. Ninety cases were classified as direct obstetrical deaths (73.77% of
      the total) and 26 (21.31%) as non-obstetrical ones. The principal causes of
      deaths were: infection, toxemia and hemorrhage. Approximately the half of the
      patients was between 16 and 25 years-old and had a parity between 2 and 4. Sixty
      two cases were considered preventable deaths (50.52%) and 36 cases probably
      preventable ones (29.51%), with a total of 98 cases (80.03%) with any possibility
      of prevention. Responsibility in these 98 deaths cases were in 52 cases (53.06%)
      on physicians and hospital and 46 cases (46.94%) on patients and community. The
      conclusion of this work is that the maternal mortality rate in this hospital is
      very high, in part because a complete registration and also because of the no
      exclusion of cases policy. These results reflects the national conditions of
      maternal health and not the one of the particular health system at which the
      hospital belongs.

PMID- 8537035
TI  - [Asthma and pregnancy].
AB  - Asthma is among the diseases that may complicate pregnancy. Asthma affects up to
      4% of the pregnant women. Uncontrolled asthma may impair the proper oxygenation
      of both mother and child. According to asthma severity clinical manifestations
      may be unapparent or apparent requiring hospital treatment. It is necessary that
      pregnant asthmatic woman check daily the peak-flow by portable peak-flow meters.
      The asthma pharmacological treatment should consider the changes in the
      physiology of the pregnancy, such as low albumin and carrier proteins for the
      drugs inducing high levels of free active drugs. This point is important for
      theophylline, besides the low drug clearance. Bronchodilator should be used as
      they are required, using the inhaled forms, as well as short term corticoid
      courses. The goal of the treatment is to control the symptoms, avoid relapse and
      keep the ventilatory function close to the normal, in order to achieve a
      satisfactory state of the mother and the children.

PMID- 8537036
TI  - [Participation of the cytoskeleton in the physiology of the endometrium].
AB  - The cytoskeleton in the endometrium, takes part not only in all the mechanic
      functions of the cell, but because of movement and location of healthy organelles
      and proteins, it also takes part in the metabolism. The endometrial epithelium,
      because of its morphology and its supposed cellular homogeneity, has been studied
      more than the stroma. It is known that intermedium filaments show a
      characteristic pattern of typical distribution and expression of the cellular
      type. During pregnancy and pseudopregnancy, in the apical region of the
      epithelial cells, both, luminal and glandular, there is an abundance of keratin
      in the basolateral region; while the vimentin is abundant only in the luminal
      epithelial cells and it increases in the implantation day. In humans and rats,
      the desmin only expresses during the decidual response. It is considered that
      intermedium filaments have a role in the polarity changes of the membrane. The
      microfilaments (MF) are related with the regulation of the cellular morphology
      and movement. In the luminal epithelium the MF play a role in the transformations
      of the uterine surface like the microvilli. The microtubules in the endometrium
      and other organs play an important role in the organelles position like
      lysosomes, mitochondria and Golgi complex. Also it is proved that take part in
      the DNA synthesis, because colchicine drug inhibits it.

PMID- 8537037
TI  - [Recurrent abdominal pregnancy. A case report].
AB  - It's a report fo a case of recurrent abdominal pregnancy attended at the
      Instituto Nacional de Perinatologia of Mexico City, the clinical manifestations,
      diagnosis, and management are described. A review of the literature is presented.

PMID- 8537038
TI  - [Gestational trophoblastic disease. A 6-year experience at the Instituto Nacional
      de Perinatologia].
AB  - From January, 1988 to March, 1994, 83 patients with diagnosis of gestational
      trophoblastic disease, were identified. Incidence was 2.4 per 1000 births.
      Average age of patients was 28.9 years. Forty four point five per cent of them
      were multiparae and in 25.3% there was the antecedent of molar pregnancy. Seventy
      seven point one per cent of the cases are from low socioeconomic stratum. The
      diagnosis was done by ultrasound in 89.1%. Instrumental uterine curettage was
      done in 89.1%, with histological confirmation in 100% of the cases. From the 83
      cases with molar pregnancy, 74 were classified as complete moles, four,
      incomplete, four, invasive and one choriocarcinoma. There was follow up in all
      the patients with beta fraction of chorionic gonadotropin hormone; this was
      negative in most of the cases for eight weeks after evacuation. Oral
      contraceptives were indicated in 73.4% of the cases.

PMID- 8537039
TI  - [The desogestrel-ethinyl estradiol combination and overweight: current data].
AB  - The effects of various progestins combined with ethynil estradiol, on body
      weight, are reviewed. A new group of obese patients being treated for weight
      excess, using desogestrel-ethynil estradiol (150 mg plus 30 mcg) as a
      contraceptive, was studied in conditions similar to those published in 1992. Very
      satisfactory results were obtained, as these patients lost body weight until
      reached ideal weight, without interference from the contraceptive compound used.

PMID- 8537040
TI  - Oestrogen and colonic epithelial cell growth.

PMID- 8537041
TI  - Nutrition support teams: an integral part of developing a gastroenterology
      service.

PMID- 8537042
TI  - Effect of curing Helicobacter pylori infection on intragastric pH during
      treatment with omeprazole.
AB  - It has been shown that omeprazole treatment produces higher intragastric pH
      values in Helicobacter pylori positive subjects than in H pylori negative
      subjects. This study aimed to investigate the effect of curing H pylori on the
      intragastric pH in both the presence and absence of omeprazole therapy. Twenty
      four hour intragastric pH recordings were performed before and after a one week
      course of omeprazole (20 mg once daily) in 18 H pylori positive subjects and were
      repeated after the infection had been cured. In the absence of omeprazole, the
      total 24 hour pH values before cure did not differ from those afterwards. During
      omeprazole treatment the 24 hour pH values were much higher before (median (95%
      CI) 5.4: 4.3, 6.0), than after cure of infection (3.6: 2.1, 4.4; p < 0.001). The
      omeprazole induced fall in H+ activity before cure of H pylori did not, however,
      differ from that afterwards. It is concluded that the apparently greater
      antisecretory effect of omeprazole during H pylori infection may be a result of
      the production of acid neutralising compounds by the H pylori. Although a direct
      interaction between H pylori and omeprazole cannot be excluded, it seems
      unlikely.

PMID- 8537043
TI  - Gastric adaptation to injury by repeated doses of aspirin strengthens mucosal
      defence against subsequent exposure to various strong irritants in rats.
AB  - Gastric adaptation to injury during repeated doses of acetyl salicylic acid (ASA)
      is a well documented finding but it is not known whether this adaptation affects
      the tolerance of the mucosa to other strong irritants. Gastric adaptation was
      induced by repeated daily doses of acidified ASA (100 mg/kg in 1.5 ml of 0.2 N
      HCl) given intragastrically (series A rats). Control rats with an intact stomach
      were given daily intragastric vehicle only (1.5 ml of 0.2 N HCl) (series B).
      After full adaptation to ASA (5 days), rats were challenged again with acidified
      ASA or, for comparison, with strong irritants such as 100% ethanol, 200 mM
      acidified taurocholate, or 25% NaCl for 1 hour or with water immersion and
      restraint for 3.5 hours. The first dose of ASA produced numerous gastric lesions
      and deep histological necrosis accompanied by a fall in the gastric blood flow,
      negligible expression of epidermal growth factor (EGF) and transforming growth
      factor alpha (TGF alpha) or their receptors, and no evidence of mucosal
      proliferation. As adaptation to ASA developed, however, the areas of gastric
      lesions were reduced by more than 80% and there was a noticeable decrease in deep
      necrosis, a partial restoration of gastric blood flow, an approximately four-fold
      increase in EGF expression (but not in TGF alpha) and its receptors, and an
      appreciable increase in mucosal cell proliferation compared with vehicle treated
      rats. Increases in the mucosal expression of EGF receptors and the luminal
      content of EGF were also found in ASA adapted animals. In ASA adapted rats
      subsequently challenged with 100% ethanol, 200 mM TC, 25% NaCl, or stress, the
      area of the gastric lesions and deep histological necrosis were appreciably
      reduced compared with values in vehicle treated rats. This increased mucosal
      tolerance to strong irritants was also accompanied by the return of the gastric
      blood flow towards control levels and further significant increases in the
      mucosal expression of EGF receptors and mucosal cell proliferation. Gastric
      adaptation to ASA enhances the mucosal resistance to injury by strong irritants
      probably as a result of the restoration of the gastric blood flow and increased
      cell proliferation that may result from increased mucosal expression of EGF and
      its receptors.

PMID- 8537044
TI  - Absence of ras gene mutations in early gastric carcinomas.
AB  - The aims of this study were to assess the prevalence and type of activating point
      mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes in a series
      of early gastric carcinomas in white patients and to correlate these ras gene
      mutations, if any, with the histological type (Lauren classification), the type
      of growth pattern, and with the Helicobacter pylori status. Haematoxylin and
      eosin and Giemsa stained sections from 45 formalin fixed, paraffin wax embedded
      early gastric carcinomas were used to assess the Lauren type, the type of growth
      pattern, and the antral H pylori status. DNA was extracted according to standard
      procedures. Mutations at codon 12 of the Ki-ras gene were examined with a
      polymerase chain reaction based restriction fragment length polymorphism (PCR
      RFLP) method and dot blot hybridisation with allele-specific 32P-labelled
      oligodeoxynucleotide (ASO) probes. All other ras genes were analysed with
      specific PCR amplification and dot blot hybridisation with ASO probes. Mutations
      were detected by overnight autoradiography at -70 degrees C. Some 20 intestinal
      type and 25 diffuse-type early gastric carcinomas were seen. According to growth
      pattern, there were 24 small mucosal type early gastric carcinomas, five
      superficial spreading type early gastric carcinomas, and 16 penetrating type
      early gastric carcinomas (four penetrating A type, 12 penetrating B type). H
      pylori was found in the antral mucosa of 28 early gastric carcinomas (62%).
      Activating ras gene mutations were not found. It was discovered that activating
      point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes do not
      play a part in the development of early gastric carcinomas in white subjects,
      irrespective of Lauren type. Moreover, differences in biological behaviour
      between early carcinomas with different types of growth pattern are not related
      to these ras gene mutations. Finally, H pylori positive and H pylori negative
      gastric carcinomas cannot be discriminated on the basis of ras gene mutational
      analysis.

PMID- 8537045
TI  - Neuroproliferation in the mucosa is a feature of coeliac disease and Crohn's
      disease.
AB  - The pathogenesis of villous damage in coeliac disease is unknown. Change to the
      delicate neuromuscular core may be significant and this study stained various
      categories of coeliac disease and controls with neuron-specific enolase (NSE) to
      examine neurofilaments in the mucosa. The amount of NSE staining was evaluated
      using computer image analysis. The first part of the study compared coeliac
      disease with Crohn's disease, carcinoma, and biopsy specimens from normal
      subjects. There was increased NSE staining in both the coeliac disease and
      Crohn's disease cases but not in carcinomas or normal controls. This difference
      was statistically significant. The average value for the coeliac disease patients
      was 50% higher than that of Crohn's disease patients. The second part of the
      study compared treated coeliac disease with untreated coeliac disease. Treated
      coeliac disease cases had normal amounts of NSE staining, which were the same as
      normal controls. These findings suggest that neuroproliferation is a feature of
      coeliac disease and Crohn's disease. Both share a common feature--namely chronic
      inflammation--which has been occasionally associated with neuroproliferation. The
      fact that neuroproliferation resolves with treatment is further evidence for its
      association with chronic inflammation. The extra neuroproliferation seen in
      coeliac disease compared with Crohn's disease may contribute to the architectural
      abnormalities seen in coeliac disease.

PMID- 8537047
TI  - Epithelial barrier and ion transport in coeliac sprue: electrical measurements on
      intestinal aspiration biopsy specimens.
AB  - Epithelial barrier function and ion transport was studied in coeliac sprue using
      a miniaturised Ussing device for measurements on diagnostic aspiration biopsy
      specimens from the jejunum of untreated or gluten free nourished sprue patients,
      or from healthy controls. Pure epithelial resistance (Re) indicating epithelial
      barrier function was determined by transmural alternating current impedance
      analysis. It was reduced by 56% in acute sprue mean (SEM) (9 (1) omega.cm2)
      compared with controls (20(2) omega.cm2). In gluten free nourished sprue patients
      Re was only partly recovered (15 (1) omega.cm2). Subepithelial resistance (Rsub)
      was also changed from 28 (1) omega.cm2- in control to 17 (1) omega.cm2 in acute
      sprue because of the change in mucosal architecture, but was unchanged in gluten
      free nourished sprue patients (29 (4) omega.cm2). In acute sprue, unidirectional
      Na+ and Cl- fluxes were increased in both directions as a consequence of the
      decreased resistance. However, short circuit current (ISC) as well as Na+ and Cl-
      net fluxes were not significantly different from control. Subsequently, the
      electrogenic Cl- secretory system was investigated. After maximal stimulation
      with theophylline and prostaglandin E1, a Cl(-)-dependent increase in ISC was
      obtained in the sprue mucosa and control jejunum. It showed saturation
      characteristics and was blockable by serosal bumetanide. When compared with
      control, neither Km nor Vmax of this electrogenic Cl- secretion was significantly
      changed in coeliac sprue. In conclusion, a miniaturised Ussing device was used
      for transport measurements on intestinal biopsy specimens. In acute coeliac
      disease, the epithelial barrier of the jejunum was seriously disturbed. The
      active electrogenic Cl- secretory transport system was present in the sprue
      mucosa, but was not activated in the Ussing chamber in vitro when compared with
      control jejunum.

PMID- 8537046
TI  - Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines
      with Th1 or Th0 profile dominated by interferon gamma.
AB  - Coeliac disease is precipitated in susceptible subjects by ingestion of wheat
      gluten or gluten related prolamins from some other cereals. The disease is
      strongly associated with certain HLA-DQ heterodimers, for example, DQ2 (DQ alpha
      1*0501, beta 1*0201) in most patients and apparently DQ8 (DQ alpha 1*0301, beta
      1*0302) in a small subset. Gluten specific T cell clones (TCC) from coeliac
      intestinal lesions were recently established and found to be mainly restricted by
      HLA-DQ2 or HLA-DQ8. Antigen induced production of cytokines was studied in 15 TCC
      from three patients, 10 being DQ2 and five DQ8 restricted. Cell culture
      supernatants were prepared by stimulation with gluten peptides in the presence of
      DQ2+ or DQ8+ Epstein-Barr virus transformed B cells as antigen presenting cells
      (APC). Supernatants were analysed for cytokines by bioassays, ELISA, and CELISA.
      Cellular cytokine mRNA was analysed semi-quantitatively by slot blotting and
      polymerase chain reaction (PCR). All TCC were found to secrete interferon (IFN)
      gamma, often at high concentrations (> 2000 U/ml); some secreted in addition
      interleukin (IL) 4, IL 5, IL 6, IL 10, tumour necrosis factor (TNF), and
      transforming growth factor (TGF) beta. The last TCC thus displayed a Th0-like
      cytokine pattern. However, other TCC produced IFN gamma and TNF but no IL 4, or
      IL 5, compatible with a Th1-like pattern. In conclusion, most DQ8 restricted TCC
      seemed to fit with a Th0 profile whereas the DQ2 restricted TCC secreted
      cytokines more compatible with a Th1 pattern. The TCC supernatants induced
      upregulation of HLA-DR and secretory component (poly-Ig receptor) in the colonic
      adenocarcinoma cell line HT-29.E10, most probably reflecting mainly the high IFN
      gamma concentrations. This cytokine, particularly in combination with TNF alpha,
      might be involved in several pathological features of the coeliac lesion. The
      characterised cytokine profiles thus support the notion that mucosal T cells
      activated in situ by gluten in a DQ restricted fashion play a central part in the
      pathogenesis of coeliac disease.

PMID- 8537048
TI  - Small bowel transplantation in children: an immunohistochemical study of
      intestinal grafts.
AB  - Seven children with short bowel syndrome underwent small bowel allografting.
      Episodes of early rejection were observed in five patients who received a graft
      from paediatric or adult donors but not in two patients who received a neonatal
      graft. This study aimed, firstly, to define immunohistochemical parameters
      accompanying rejection and, secondly, to compare immunohistochemical parameters
      in neonatal grafts with those in grafts from older donors. An immunohistochemical
      analysis was performed on 85 intestinal biopsy specimens taken for monitoring the
      transplant. Acute histological rejection was associated with pericryptic
      infiltrates of CD3+TcR alpha beta + T cells containing clusters of CD8+ cells,
      numerous CD25+ cells, and increased numbers of CD68+ macrophages. These changes
      were associated with the appearance of major histocompatibility (MHC) class II
      antigens on crypt enterocytes and with an appreciable increase in the expression
      of E-selectin on mucosal endothelial cells. Immunohistochemistry was useful in
      predicting rejection by showing the appearance of pericryptic CD25+ T cells 48
      hours before the first histological lesions of crypt necrosis. Comparison of
      neonatal grafts with grafts from older donors did not show any significant
      difference in the density of CD68+ macrophages or in the endothelial expression
      of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or E
      selectin. In contrast to grafts from older donors, however, neonatal grafts did
      not express MHC class II antigens on epithelial cells and contained very low
      numbers of intraepithelial lymphocytes. These data indicate, firstly, that
      immunohistochemistry is useful for monitoring intestinal transplants and,
      secondly, that the better clinical tolerance of neonatal allografts may be
      related to the lower immunogenicity of the neonatal epithelium.

PMID- 8537049
TI  - Gut intramucosal pH and intraluminal PO2 in a porcine model of peritonitis or
      haemorrhage.
AB  - The tonometric method of detecting decreased gut intramucosal pH (pHi) is based
      on the fact that carbon dioxide can diffuse through the wall of the silastic
      balloon of the tonometer. By using deoxified saline and measuring PO2 as well as
      PCO2 this study aimed to follow changes in mucosal PO2 and relate them to changes
      in pHi in peritonitis versus haemorrhage. Twenty five pigs were used. Five were
      controls, in 10 peritonitis was induced by the instillation of faeces in the
      abdominal cavity, and 10 were bled, half of them stepwise during three hours, and
      half of them rapidly down to a mean (SEM) arterial pressure of 30 (10) mm Hg. The
      drop in pHi correlated well with decreasing intraluminal PO2 (r = 0.63 (0.13)) in
      haemorrhage. In peritonitis this drop occurred within a very limited change in
      intraluminal PO2 (r = 0.06 (0.17)). Thus oxygen seemed to be present in the
      mucosa at the same time as there were signs of anaerobic metabolism as evidenced
      by a low intramucosal pH. Impaired oxygen extraction or utilisation, or both, is
      proposed as an explanation to this seemingly paradoxical situation.

PMID- 8537050
TI  - Inability of normal human intestinal macrophages to form multinucleated giant
      cells in response to cytokines.
AB  - Multinucleated giant cells are an important feature of the granulomatous reaction
      in Crohn's disease (CD) but their cellular origin is poorly understood. The aim
      of this study was to discover if intestinal macrophages are capable of generating
      multinucleated giant cells in vitro in response to cytokine stimulation. Human
      intestinal macrophages were isolated from the intestinal mucosa of CD and
      uninflamed surgical specimens. Isolated macrophages were cultured in chamber
      slides with and without exposure to a panel of cytokines and cell activators.
      Cell fusion, multinucleated giant cells formation, and the expression of adhesion
      molecules were assessed at various time intervals. In contrast with the
      autologous peripheral monocytes cell fusion was very poor in cultures of control
      intestinal macrophages and virtually no multinucleated giant cells were seen.
      Control intestinal macrophages seemed to poorly express the adhesion molecules
      required for cell to cell adhesion and fusion, namely ICAM-1 and LFA-1. None of
      these functions was affected by the exposure to cytokines, including interferon
      gamma. In cultures of macrophages isolated from CD tissues multinucleated giant
      cell formation spontaneously occurred as early as three days and was not enhanced
      by the addition of cytokines. CD macrophages seemed to highly express both ICAM-1
      and LFA-1. These data show that human intestinal macrophages are unable to form
      multinucleated giant cells in response to stimuli and support the concept that
      they are downregulated in a number of functions. The data also suggest that
      macrophages participating in the ganulomatous reaction in CD are recruited from
      the circulation.

PMID- 8537051
TI  - p53 expression in ulcerative colitis: a longitudinal study.
AB  - p53 Mutation is a late event in the development of sporadic colorectal carcinoma
      (CRC). The timing of p53 mutations in the development of ulcerative colitis
      associated colorectal carcinoma (UCACRC) is, however, less certain and some
      reports suggest that it may be a relatively early event. This study sought to
      establish the timing of p53 mutations in neoplasia arising in ulcerative colitis.
      Blocks of 10 resected colorectal specimens from patients who had had a biopsy
      positive for dysplasia at least one year prior to resection were retrieved from
      the archives of St Mark's Hospital. Immunochemistry using the monoclonal antibody
      DO-7, specific for both mutant and wild type p53, was performed on sections from
      both the resection specimens and dysplastic biopsy specimens. Seven of the 10
      resection specimens were positive for p53. Two of these seven specimens showed
      p53 overexpression in specimens taken two years before the development of
      carcinoma or high grade dysplasia. Five of the seven specimens were negative for
      p53 overexpression between one and four years prior to resection. These results
      suggest that p53 overexpression is usually a late event in the development of
      UCACRCs.

PMID- 8537052
TI  - Seromarkers of collagen I and III metabolism in active Crohn's disease. Relation
      to disease activity and response to therapy.
AB  - Crohn's disease is characterised by gradual development of intestinal fibrotic
      lesions containing large amounts of collagen type I, III, and V. Measurement of
      circulating connective tissue metabolites has emerged as a useful tool for
      assessment of fibroproliferative activity in various diseases. Serum
      concentrations of procollagen peptides, N-terminal propeptide of type III
      procollagen (PII-INP), and C-terminal propeptide of type I procollagen (PICP),
      reflect the synthesis rate of the parent collagens, while the C-terminal
      telopeptide of type I collagen (ICTP) reflects its degradation. S-PIIINP, S-PICP,
      and S-ICTP were measured by radioimmunoassays in 29 patients with active Crohn's
      disease. S-ICTP was significantly increased, median 6.2 micrograms/l (95% CI 5.2
      to 8.7 micrograms/l) versus controls 2.6 micrograms/l (2.5 to 2.7 micrograms/l)
      (p < 0.0001), S-PICP reduced, 100 micrograms/l (80 to 110 micrograms/l) versus
      132 micrograms/l (124 to 141 micrograms/l) (p = 0.001), and S-PIIINP did not
      differ from controls. Patients with sustained clinical remission during
      prednisolone therapy exhibited an increase in S-PICP (p = 0.0052). S-PIIINP
      changed significantly (p = 0.0002), however, exhibiting a biphasic pattern. S
      ICTP decreased (p = 0.015) in treatment responders but remained above the upper
      normal limit even when clinical remission had been achieved. Non-responders
      showed no significant changes in any of the marker molecules of collagen
      synthesis or degradation. Correlations were found between S-PIIINP and S-PICP (p
      < 0.005) and S-ICTP (p < 0.02), and between S-ICTP and S-orosomucoid (p < 0.005)
      and S-C reactive protein (p < 0.02). By contrast, there was no relation between
      the connective tissue metabolites and Harvey Bradshaw Index. These data provide
      evidence that collagen I degradation is increased not only in active Crohn's
      disease, but also in patients entering clinical remission. The concurrent
      normal/low-normal values of markers of collagen formation may reflect a changed
      local or systemic elimination of the propeptides.

PMID- 8537053
TI  - Identifying patients with a high risk of relapse in quiescent Crohn's disease.
      The GETAID Group. The Groupe d'Etudes Therapeutiques des Affections
      Inflammatoires Digestives.
AB  - No reliable identification of quiescent Crohn's disease (CD) patients with a high
      risk of relapse is available. The aim of this study was to develop a prognostic
      index to identify those patients. Untreated adult patients with quiescent disease
      (not induced by surgery) included in three phase III clinical trials were
      analysed retrospectively with respect to time to relapse. Nineteen factors
      related to biology, disease history, and topography were investigated. A relapse
      was defined as either a CD Activity Index (CDAI) > or = 200, a CDAI > or = 150
      but over the baseline value by more than 100, or acute complications requiring
      surgery. The inclusion criteria were fulfilled by 178 patients. The median follow
      up was 23 months. The Cox model retained the following bad prognostic factors:
      age < or = 25 years, interval since first symptoms > 5 years, interval since
      previous relapse < or = 6 months, and colonic involvement (p < 0.001).
      Bootstrapping confirmed the variable selection. Patients were classified into
      three groups with an increasing risk of relapse (p < 0.001). The worst risk group
      was composed of patients presenting at least three of the four bad prognostic
      factors. These results make possible the design of clinical trials in quiescent
      CD patients with a high risk of relapse.

PMID- 8537054
TI  - In situ detection of enterocytic apoptosis in normal colonic mucosa and in
      familial adenomatous polyposis.
AB  - Physiological regeneration of colonic epithelium entails proliferation at the
      crypt base and cell loss by shedding or cell death. The aim of this study was to
      localise and assess the rate of apoptosis in normal and neoplastic colonic
      epithelium with respect to zones of proliferation. Familial adenomatous polyposis
      (FAP) was chosen as a model to study neoplastic transformation of colonic mucosa
      at an early stage. Apoptotic cells were detected in situ by TdT-mediated biotin
      dUTP nick end labelling (TUNEL) in parallel to cells in cycle determined by Ki-67
      immunohistochemistry using the monoclonal antibody MiB-1. By detection of genomic
      fragmentation, two different patterns of enterocytic apoptosis emerged: (a)
      apoptotic bodies being engulfed by adjacent epithelial cells, and (b) apoptotic
      cells with only subtle morphological changes being extruded into the gut lumen.
      The engulfment pattern was seen predominantly in the crypts of the normal colonic
      mucosa and, although very rare, was clearly confined to the basal proliferation
      compartment. The extrusion pattern was restricted to the luminal mucosal surface.
      Adenomas of FAP showed highly increased numbers of apoptotic bodies, which were
      scattered throughout the transformed mucosa. Both patterns of apoptosis were
      topographically intermingled although the extrusion pattern prevailed at the
      luminal adenoma surfaces. Whereas cells in cycle were somewhat more numerous in
      the upper parts of the crypts, apoptosis occurred with increased frequency at
      sites beneath the proliferation maximum suggesting an inverted direction of
      epithelial cell migration in adenomas. These results suggest two distinct routes
      towards enterocytic apoptosis in the colonic mucosa leading to engulfment or
      extrusion of dying cells. Adenomatous transformation of colon epithelium is
      associated with a considerable increase of the cellular turnover rate and with a
      severe disturbance of the microtopographical localisation of birth and death of
      enterocytes.

PMID- 8537055
TI  - Expression of the APC gene after transfection into a colonic cancer cell line.
AB  - Mutations in the adenomatous polyposis coli (APC) gene cause the hereditary
      cancer syndrome familial adenomatous polyposis and are implicated in the early
      stages of sporadic colorectal carcinogenesis. APC is therefore a promising
      candidate for use in prophylactic gene therapy of intestinal tissues at high risk
      of becoming malignant. The aim of the study was to discover if functional full
      length APC gene can be introduced into somatic gut epithelial cells and to define
      the optimum conditions for such transfer. Copies of the normal APC gene were
      introduced into SW480 cells, a colonic epithelial cell line with an APC gene
      mutation, using plasmid DNA combined with liposomes. Reverse transcriptase
      polymerase chain reaction and restriction enzyme digestion allowed the endogenous
      gene to be distinguished from the transgene. It was shown that the normal APC
      gene is expressed at high levels for 72 hours after transfection and disappears
      within one week. This study shows that short-term expression of normal APC gene
      can be achieved after transfection with liposome-DNA complexes at sufficiently
      high levels to permit assessment of biological effects.

PMID- 8537056
TI  - Family history of colorectal tumours and implications for the adenoma-carcinoma
      sequence: a case control study.
AB  - Family history of colorectal cancer is a risk factor for sporadic colorectal
      cancer, but it is not known which step of the adenoma-carcinoma pathway it
      influences. This case control study investigated the relation between family
      history of cancer and colorectal adenomas and cancers. Family history of
      colorectal cancer (FHCRC) was as frequent in small (< 10 mm) adenoma patients
      (11.7%, n = 154) as in polyp free patients (10.6%, n = 426), whereas it was more
      frequent in patients with large adenoma(s) (18.8%, n = 208; p < 0.01). Odds
      ratios for FHCRC were 1.2 (p > 0.10) for small adenomas and 2.1 (p < 0.01) for
      large adenomas. Family history of other (non-colorectal) cancers (FHOC) was
      similar in the three groups. Patients with a colorectal cancer (n = 171) had more
      frequently a family history of cancer, both colorectal (15.8%; p < 0.01) and
      other cancers (35.7%; p < 0.001) than general population controls (n = 309;
      FHCRC: 8.1%; FHOC: 21.7%). In a logistic model, both factors were independently
      related to colorectal cancers (odds ratios: 1.9 (p < 0.05) for FHCRC and 2.1 (p <
      0.001) for FHOC). These data suggest that family history of colorectal cancer
      influences only the growth of adenomas or their malignant transformation. The
      finding of a further predisposition to any type of cancer needs to be confirmed.

PMID- 8537057
TI  - Embolotherapy for massive upper gastrointestinal haemorrhage secondary to
      metastatic renal cell carcinoma: report of three cases.
AB  - Three cases are reported in which angiographic embolisation therapy was effective
      in arresting upper gastrointestinal bleeding secondary to metastatic
      hypernephroma. Each patient had histologically confirmed disseminated renal cell
      carcinoma and presented with recurrent haematemeses with a successful outcome
      following palliative embolisation therapy.

PMID- 8537058
TI  - Mesalazine induced exacerbation of ulcerative colitis.
AB  - 5-Aminosalicylic acid (5-ASA) compounds occasionally exacerbate diarrhoea in
      patients with inflammatory bowel disease. This is thought to be due to a
      secretory mechanism in most cases. A patient with presumed intolerance to
      sulphasalazine and 5-ASA preparations who developed endoscopic and histological
      evidence of disease relapse after a rectal challenge with mesalazine is reported.

PMID- 8537059
TI  - Ileostomy polyps, adenomas, and adenocarcinomas.
AB  - Ileostomy polyps are uncommon and poorly described. The aim of this study was to
      undertake a retrospective clinicopathological review of ileostomy polyps. Seven
      patients with 60 polyps arising on ileostomies performed for ulcerative colitis
      were studied. The histopathological evaluation of archival ileostomy biopsy
      specimens, polypectomy or excision specimens, and clinical review of patient
      records was undertaken. Fifty of 60 polyps were inflammatory cap polyps and six
      further polyps were composed of granulation tissue only. They occurred anywhere
      on the stoma at any time after ileostomy construction and were strongly
      associated with overt stomal prolapse. Four neoplastic polyps were identified in
      two patients 27-36 years after ileostomy construction; all occurred at the
      mucocutaneous junction. One patient presented with a 2 cm polypoid invasive
      adenocarcinoma while in the second a 1.7 cm polypoid mucinous adenocarcinoma and
      a 0.7 cm ileal tubular adenoma with high grade dysplasia occurred at the site of
      excision of a cap polyp showing focal low grade adenomatous dysplasia six years
      previously. Neoplastic and non-neoplastic polyps could not be differentiated
      clinically. It was found that most ileostomy polyps are inflammatory cap polyps
      associated with stomal prolapse. Less common are polypoid adenomas or
      adenocarcinomas arising at the mucocutaneous anastomosis > 20 years after
      ileostomy construction. To prevent ileostomy carcinoma it is recommended that a
      biopsy of all polyps at the mucocutaneous anastomosis and of any non-prolapse
      associated polyps elsewhere on the stoma occurring > 15 years after ileostomy
      construction is done.

PMID- 8537061
TI  - Helicobacter pylori and cholecystectomy.

PMID- 8537060
TI  - Restorative proctocolectomy and pouch anal anastomosis for ulcerative colitis
      following orthotopic liver transplantation.
AB  - This study reports on the outcome of four patients having ileal pouch anal
      anastomosis after orthotopic liver transplantation for sclerosing cholangitis
      complicating ulcerative colitis. There were no deaths on follow up. Early
      postoperative bleeding was a complication of colectomy or rectal excision in
      three, one of whom developed hepatic artery thrombosis and the overall
      complication rate was high. All patients are continent but one has chronic
      pouchitis (while receiving longterm metronidazole) and one patient has recurrent
      sclerosing cholangitis in the transplant.

PMID- 8537062
TI  - Pancreatic vascular regulation.

PMID- 8537063
TI  - The morphological aspects of the innervation of the external urethral striated
      sphincter.
AB  - Innervation of the sphincter urethrae externus muscle was studied in 30 human
      fetuses with the aid of operation microscope. The investigated muscle receives
      direct branch from anterior roots of S2, S3, or S4, or from the trunk of the
      pudendal nerve. The branch to the muscle divides into 2 or 3 rami before it
      enters the muscle, or it divides into 2 or 3 terminal rami, and gives off the
      dorsal nerve of the penis or clitoris.

PMID- 8537064
TI  - Fasciculus intramedullaris accessorius in the development of the human embryonic
      spinal accessory nerve.
AB  - In embryos at stage 16 (37 days) the intramedullary roots of the spinal accessory
      nucleus ascend in the marginal layer of the spinal cord within one segment. These
      fibers form the intramedullary accessory fascicle of the XIth nerve. This
      fasciculus was observed in further developmental stages of investigated embryos.

PMID- 8537065
TI  - The usage of infrared, ultraviolet and image computer transformation system in
      human cerebral angiologic examinations.
AB  - The usage of infrared, ultraviolet, luminescence both in infrared and ultraviolet
      for anatomical purposes was studied and the films were transformed with image
      computer analysis system. Infrared turned out to be exceptionally useful for
      examination of deep structures. Ultraviolet and especially luminescence in
      ultraviolet enables tracing the elements placed on the surface. Image computer
      transformation makes possible the spatial assessment of selected details and it
      broadens the exploratory possibilities.

PMID- 8537066
TI  - Vascularization of the brain in guinea pig. II. Regions of vascular supply and
      spatial topography of the arteries in particular parts of the brain.
AB  - It was shown that the parts of the brain in guinea pig are supplied through
      internal branches arising from the vertebral, basilar, and internal cartoid
      arteries. The medulla oblongata and pons receive branches originating from the
      anterior and posterior spinal arteries as well as from the inferior cerebellar
      arteries. The cerebellum reach rami arising from all cerebellar arteries.
      Mesencephalon is supplied by superior cerebellar, posterior cerebral, posterior
      communicating, and choroid arteries. The diencephalon receives branches from all
      three cerebral, posterior communicating, and choroid arteries. Telencephalon
      receives blood supply from three cerebral arteries as well as from posterior
      communicating and choroid vessels.

PMID- 8537067
TI  - Morphological analysis of the myocardial fiber architecture of ventriculus cordis
      in normal and malformed human hearts.
AB  - In this study, ten normal and one malformed adult human hearts obtained from the
      collections of Gazi University Department of Anatomy were investigated. Muscle
      maceration techniques of Romeis and Torrant-Guasp have been used. In the normal
      heart, the superficial layer of ventricular myocardium has been detected. Then,
      middle layer was demonstrated by lifting up the fibers of this layer. Endocardium
      of ventricles was dissected and inner layer was observed. Consequently, direction
      of muscle fibers was examined in ventricular myocardium. Sections of muscle
      samples from an hypertrophied heart were prepared by routine light microscopic
      procedures. In the normal heart, a thin middle layer was present in right
      ventricle. This layer was appeared to be hypertrophied in the malformed heart.

PMID- 8537068
TI  - Arterial vascularization of the interatrial septum in the human heart in relation
      to the type of coronary ramification.
AB  - On 130 randomized specimens of human heart, of both sexes (19-86 years of age) I
      have investigated the vascularization of the interatrial septum of the heart in
      relation to the type of coronary arteries ramifications using dissection and
      injection-corrosion methods. The interatrial septum is supplied by the right and
      left anterior atrial branches and right and left posterior atrial branches. The
      blood supply of the posterior part of the interatrial septum is related to the
      type of the arterial vessels of the heart. Anastomoses between branches of the
      right and left coronary arteries occur in the septum.

PMID- 8537069
TI  - Collateral respiratory pathways of pulmonary acini in man.
AB  - Using corrosion casts of 5 lungs which bronchial tree was filled with plastogen
      G, four forms of collateral respiratory pathways were seen: the interalveolar,
      the bronchioloalveolar in the same acinus, the bronchioloalveolar between
      adjoining acini, and the intersegmental communications.

PMID- 8537070
TI  - On a rare form of fenestration of the middle cerebral artery.
AB  - A rare case of fenestration of the left middle cerebral artery (MCA) is
      presented. There is a coexistence with hypoplasia of precommunicans part of the
      right posterior cerebral artery and its "fetal" branching from internal carotid
      artery. This form of variation may cause mistakes during interpretation of
      angiographic investigation.

PMID- 8537071
TI  - [Analysis of receptor-ion channel functions in Xenopus oocyte translation
      system].
AB  - Xenopus oocytes has been utilized to analyze the intracellular signaling and
      coupling mechanisms between neurotransmitter receptors and ion channels. (1) The
      GTP-binding protein-coupled intracellular signaling pathway was analyzed in
      oocytes expressing metabotropic receptors by brain mRNA. These metabotropic
      receptors are commonly linked to the sequence of phosphoinositide metabolism,
      intracellular Ca2+ increase and opening of Ca(2+)-dependent Cl- channels. An
      antisense DNA study indicated that a specific subtype of GTP-binding protein is
      involved in the coupling of each metabotropic receptor. (2) Effects of central
      acting drugs on the functions of glutamate receptor subtypes and voltage
      dependent Ca2+ channels were evaluated, and the data were compared with the
      results from conventional in vitro assays using brain preparations. (3) A series
      of experiments on kappa-opioid receptors indicated that kappa-opioid receptors
      can couple with multiple signaling systems in the oocytes via GTP-binding
      proteins Gi/G(o), which involves mobilization of intracellular Ca2+ through
      phosphoinositide metabolism, synergistic potentiation of cyclic AMP production,
      and inhibition of voltage-dependent Ca2+ channels.

PMID- 8537072
TI  - [Flow cytometry and laser scanning confocal microscopy analysis of the receptor
      distribution].
AB  - To study the physiological regulation of the receptor protein, a fluorescent
      probe and detection system for alpha 1B-adrenergic receptors have been developed.
      By using the anti-peptide antibody developed against the alpha 1B-adrenergic
      receptor NH2-terminus, we have examined the agonist-regulated alpha 1B-adrenergic
      receptor redistribution in desensitized cells. Flow cytometry analysis showed
      that anti-peptide antibody against alpha 1B-adrenergic receptor specifically
      identifies the receptor in CHO cells, COS-7 cells that were transfected with
      alpha 1B-adrenergic receptor cDNA and rat hepatocytes. Using a fluoro-labeled
      receptor ligand, BODIPY FL-prazosin, as a probe, cell surface alpha 1-adrenergic
      receptor subtypes can be detected by flow cytometry. Laser scanning confocal
      microscopy visualized the agonist-regulated redistribution process of alpha 1B
      adrenergic receptor in living cells; thus, following phenylephrine (10(-6) M)
      stimulation, receptor antigen at the cell surface rapidly internalized and
      clustered together in a cell within 30 min. The results showed that the antibody
      and fluoro-labeled ligand are valuable tools for studying the localization and
      functional role of the alpha 1-adrenergic receptor subtype.

PMID- 8537073
TI  - [Effect of efonidipine hydrochloride (NZ-105) on modification of low density
      lipoprotein induced by rat cultured endothelial cells].
AB  - We studied the effects of efonidipine hydrochloride [NZ-105: (+/-)-2-[benzyl
      (phenyl) amino] ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2
      dioxaphosphorina n-2- yl)-4-(3-nitro-phenyl)-3-pyridinecarboxylate hydrochloride
      ethanol] and nisoldipine on endothelial cell-induced low density lipoprotein
      (LDL) modification. The modification of LDL by cultured rat endothelial cells was
      performed by incubating 3 micrograms protein/well LDL with 5 microM CuSO4 for 24
      hr at 37 degrees C in the presence of confluent cells. The extent of modification
      was assayed by measuring the thiobarbituric acid-reactive substances (TBARS).
      Efonidipine hydrochloride reduced the TBARS level in a dose-dependent manner. At
      3 x 10(-7) M, efonidipine hydrochloride showed a significant effect. On the other
      hand, the significant effect of nisoldipine was observed only at 10(-5) M. Thus
      the action of efonidipine hydrochloride on the inhibition of LDL-modification was
      much more potent than that of nisoldipine. As the modification of LDL was thought
      to play a key role in the initiation and progression of atherosclerosis,
      efonidipine hydrochloride may be useful against atherosclerosis.

PMID- 8537074
TI  - [Mechanism of analgesic action of Y-23023, a new non-steroidal anti-inflammatory
      drug].
AB  - The analgesic mechanism of Y-23023, a new non-steroidal anti-inflammatory drug,
      was investigated in the writhing response induced by intraperitoneal injection of
      kaolin and captopril in mice. Y-23023 (0.1-1 mg/kg, p.o.) suppressed the writhing
      frequency in a dose-dependent manner. Y-23023 also significantly reduced the
      increased levels of prostaglandin (PG) and bradykinin (BK) in the peritoneal
      cavity. In contrast, indomethacin, diclofenac sodium, loxoprofen sodium and
      mefenamic acid inhibited the writhing response, but their efficacies were lower
      than that of Y-23023. The peritoneal PG levels were dose-dependently reduced to
      the same extent as Y-23023, whereas the BK levels were not. M1, an active
      metabolite of Y-23023, inhibited the cyclooxygenase from sheep vesicular gland in
      a concentration-dependent manner, and its potency was similar to that of
      indomethacin. These results suggest that in addition to the suppressive effect on
      PG production via inhibition of cyclooxygenase, the inhibitory effect on BK
      production is involved in the analgesic action of Y-23023, unlike indomethacin
      and diclofenac sodium.

PMID- 8537075
TI  - [Antihypertensive effects of repeated oral administration of cilnidipine, a novel
      calcium antagonist, in 2K1C renal hypertensive dogs].
AB  - Antihypertensive effects of repeated oral administration of cilnidipine in 2K1C
      renal hypertensive dogs were compared with those of nicardipine. On the first
      day, oral administration of cilnidipine (3 mg/kg) or nicardipine (3 mg/kg)
      markedly lowered both systolic and diastolic blood pressure 1 hr after
      administration. The hypotensive effects of cilnidipine were longer compared with
      those of nicardipine. Both drugs elevated the heart rate and plasma renin
      activity. On the 8th and 15th days, similar responses were obtained by repeated
      administrations of cilnidipine and nicardipine. After withdrawal of these drugs,
      no rebound phenomena in blood pressure were observed. The changes in mean blood
      pressure were correlated with plasma cilnidipine or nicardipine concentrations
      that were obtained at each time of blood pressure measurement (r = -0.598; P <
      0.001 and r = -0.594; P < 0.001, respectively). These results suggest that stable
      and long-acting antihypertensive effects of cilnidipine for 15 consecutive days
      in renal hypertensive dogs are related to the change in plasma drug
      concentrations.

PMID- 8537076
TI  - [Pharmacological studies on KW-4679, an antiallergic drug. (1): Inhibitory effect
      on passive cutaneous anaphylaxis (PCA) and experimental asthma in rats and guinea
      pigs].
AB  - The present experiment was carried out to elucidate the antiallergic properties
      of KW-4679. Oral administration of KW-4679 showed a dose-dependent inhibition on
      the IgE-mediated 48-hr homologous PCA in rats, with an ID50 value of 0.04 mg/kg.
      Passive anaphylactic broncho-constriction in guinea pigs mediated by IgE-like
      homologous antibody against ovalbumin was prevented dose-dependently by treatment
      with KW-4679 at doses of 0.03-1 mg/kg, p.o. KW-4679 also inhibited the IgE
      mediated active anaphylactic bronchoconstriction in rats. In passively sensitized
      guinea pigs, the inhalation of aerosol antigen decreased the dynamic compliance
      of the lung and increased the mean pulmonary resistance. Pretreatment with KW
      4679 (0.03-1 mg/kg, p.o.) inhibited antigen-induced airway obstructions. Oral
      administration of KW-4679 significantly protected rats from compound 48/80
      induced lethality. These results indicate that KW-4679 might be useful in the
      treatment of allergic diseases such as asthma.

PMID- 8537077
TI  - Five restriction fragment length polymorphisms of the APOA1-C3 gene and their
      influence on lipids and apolipoproteins in healthy Chinese.
AB  - The distribution of five restriction fragment length polymorphisms (RFLPs) of the
      APOA1-C3 gene cluster and their influence on serum lipids and apolipoprotein
      levels was investigated in 151 healthy Chinese of both sexes. The frequencies of
      the rare alleles at ApaI, BanI, XmnI (A1) and SstI (C3) sites were significantly
      different in the Chinese when compared to Caucasians as follows: ApaI: 0.25 vs.
      0.42 (p < 0.02); BanI: 0.33 vs. 0.16 (p < 0.01); XmnI: X2, 0.30 vs. 0.14, and X3,
      0.08 vs 0.05 (p = 0.001); SstI (C3): 0.23 vs. 0.12 (p = 0.011). The frequency of
      P2 (PstI) at 0.04 was similar to that in Caucasians (0.07). The distribution of
      the genotypes of all the RFLPs was in Hardy-Weinberg equilibrium in this
      population. A significant association of the SstI polymorphism of the C3 region
      with the serum high-density lipoprotein (HDL)-cholesterol level was observed in
      both men and women, the rarer allele (S2) being associated with higher levels (p
      < 0.05). 5.8% of the sample variance of the HDL-cholesterol level in this sample
      could be explained by the SstI polymorphism of the C3 region (F = 6.07, p =
      0.003). The association of the SstI locus with serum HDL-cholesterol was stronger
      in males than in females (R2 = 13.8 and 6.7%, respectively). There was a similar
      trend of association of the serum apolipoprotein A-I level with the SstI
      polymorphism, though it did not reach statistical significance. There was no
      association between the levels of any of the lipid and apolipoproteins studied
      with RFLPs of the APOA1 gene.

PMID- 8537078
TI  - Nonparametric tests for linkage with dependent sib pairs.
AB  - Sib pair tests for linkage to a quantitative trait or affection status are
      examined by simulation. A sibship of size s contributes only s-1 independent sib
      pairs but all s(s-1)/2 pairs are needed for an efficient test. Redundancy
      increases with sibship size. Using simulated data on the null hypothesis of no
      linkage, we have considered equal and unequal weights. Unequal weights lose power
      as measured by the equivalent number of observations, and goodness of fit to the
      theoretical distribution is degraded. The Fisher z(r) test with equally weighted
      pairs is more reliable than any t(r) test based on conjectured degrees of
      freedom, but significance levels must be established by simulation if the number
      of pairs is small or redundancy is large. An approach to parametric analysis
      through nuisance parameters is discussed.

PMID- 8537079
TI  - Subtyping of coagulation factor XIIIA.
AB  - An extended polymorphism of the coagulation factor XIIIA can routinely be
      detected in human plasma samples and white cell lysates by isoelectric focusing
      in polyacrylamide gels containing 3 M urea in the pH range 5-8. Analyses of 184
      families with 513 children confirmed the formal model proposed by Suzuki et al.
      [Am J Hum Genet 1988;43:170-174]. Four common alleles, F XIIIA*1A, 1B, 2A, 2B, at
      an autosomal locus control the expression of ten phenotypes. On the basis of the
      population sample from southwest Germany the frequencies of the common alleles F
      XIIIA*1A, 1B, 2A, 2B were calculated as 0.175, 0.609, 0.011, and 0.205,
      respectively.

PMID- 8537080
TI  - An incremental algorithm for efficient multipoint linkage analysis.
AB  - While much effort has gone into developing efficient algorithms for calculating
      multipoint likelihoods, these calculations still form a significant bottleneck in
      the construction of genetic linkage maps. Our approach to this problem is based
      on incremental processing techniques, which attempt to reduce the time required
      to perform iterative computations by storing intermediate results during the
      initial iteration, so that they may be reused with little extra computation in
      subsequent iterations. We have developed an incremental program which provides a
      more efficient substitute for the CMAP program of the LINKAGE package. Our
      incremental approach stores intermediate results of the computations in the form
      of a rational function. Thus, computing the likelihood for one position of an
      unmapped marker locus requires only the reevaluation of the rational function.
      Timing data suggest that when pedigrees are fully or nearly fully typed, our
      program runs about 3-fold faster than CMAP to compute the likelihood for one
      position of a marker locus. Additional positions do not add any appreciable time
      to our program; thus, speedups become more pronounced as more marker locus
      positions are considered.

PMID- 8537081
TI  - A program using loss-of-constitutional-heterozygosity data to ascertain the
      location of predisposing genes in cancer families.
AB  - We present a modification of the MLINK program, which enables the formal
      incorporation of data on loss of constitutional heterozygosity (LOCH) into
      likelihood calculations. This is an implementation of a previously described
      approach to localise tumour suppressor genes involved in inherited cancer
      predisposition. LOCH data are treated as additional observations on disease
      phenotype. The main effect of including extra data is to enhance the power to
      detect linkage. In this way, the method facilitates the use of small families, in
      particular parent-offspring pairs, which would otherwise be uninformative. The
      technique also has an advantage in view of the increasing use of archival
      material, which is often derived from specimens taken for histopathological
      analysis, and may contain tumour tissue which can also be used to obtain
      additional information. We describe the use of the program, the interpretation of
      the results and the advantages and limitations of this approach.

PMID- 8537082
TI  - Molecular variants of red cell glucose-6-phosphate dehydrogenase deficiency in
      Central Java, Indonesia.
AB  - One hundred and sixty-nine Javanese males were screened for the presence of red
      cell glucose-6-phosphate dehydrogenase (G6PD) variants by a dye decoloration
      screening test and starch gel electrophoresis. The frequency of G6PD deficiency
      was 14%. Three non-deficient electrophoretic variants with mobilities of 95, 105
      and 107% of GdB+ were encountered. Sixteen G6PD-deficient subjects were further
      investigated for the presence of mutations at nt95 A-->G, nt487 G-->A, nt493 A-
      >G, nt563 C-->T, nt1024 C-->T, nt1376 G-->T, nt1388 G-->A and the silent mutation
      (nt1311 C-->T) of the G6PD gene by natural or artificially created amplified
      restriction sites. They were identified by the polymerase chain reaction and
      electrophoresis of restriction-digested products. Five subjects had the
      Mediterranean mutation (nt563 C-->T), but only one had simultaneous presence of
      nt1311(T). The next common mutations were 1376(T) in three subjects and 487(A) in
      two subjects. Five of the sixteen subjects had the nt1311(T) mutation giving an
      overall frequency of 0.31. The other four mutations were absent in this
      population sample.

PMID- 8537083
TI  - Alpha-1-antitrypsin subtypes in Polish newborns.
AB  - Alpha-1-antitrypsin phenotypes of umbilical cord serum from 741 Polish newborns
      were studied by isoelectric focusing. The frequencies of the PI alleles were:
      PI*M1 = 0.7199, PI*M2 = 0.1613, PI*M3 = 0.0965, PI*S = 0.0094, PI*Z = 0.0067, and
      PI*Var(F,I,L) = 0.0060. The data obtained for Poland were compared to those for
      other European populations.

PMID- 8537084
TI  - Competition inhibition of cytotoxic T-lymphocyte (CTL) lysis, a more sensitive
      method to identify candidate CTL epitopes than induction of antibody-detected MHC
      class I stabilization.
AB  - We compared the efficiency of two commonly used cellular major histocompatibility
      complex (MHC) class I peptide-binding assays to identify a cytotoxic T lymphocyte
      (CTL) epitope-containing peptide among length variants derived from the human
      papilloma virus type 16 (HPV 16) oncoprotein E7. Although both assays identified
      the same sequence (E7 49-57) as the most efficient Db-binding peptide, the
      efficiency by which they did so differed markedly. In a peptide competition
      cytotoxicity (PCC) assay, based on inhibition of CTL lysis by competition for
      binding to MHC class-I molecules between a known CTL epitope-containing peptide
      and peptide of interest, E7 49-57 bound 45-fold more efficiently to Db than the
      second Db-binding peptide in line. In the widely used RMA-S MHC class I peptide
      binding assay, based on peptide-induced stabilization of 'empty' MHC class-I
      molecules at the surface of antigen-processing defective RMA-S cells, this
      difference was only 3 fold. Similar differences were observed when other Db
      restricted CTL clones and CTL epitope-containing peptides were used in the PCC
      assay. The same phenomenon was observed when peptide binding affinities for H-2Kb
      were analyzed in both assays. We conclude that the PCC assay discriminates more
      efficiently between high- and low-affinity MHC class I binding peptides than the
      RMA-S assay. This observation is ascribed to the fact that peptide-MHC class I
      dissociation is an important parameter in the PCC but not the RMA-S assay.

PMID- 8537085
TI  - Effect of cytokines on 5-fluorouracil-mediated immunosuppression.
AB  - The effect of cytokines on 5-fluorouracil-mediated suppression of antibody
      response to arsanilic acid-bovine gammaglobulin (ARS-BGG) in high- and low
      responding strains of mice was determined. Single i.v. injections of 5
      fluorouracil strongly inhibited both primary and secondary antibody responses.
      The high-responding strain was found to be more sensitive to 5-fluorouracil.
      Restoration of suppressed IgG antibody responses to ARS-BGG was achieved in vitro
      by addition of either rIL-4, or rIFN gamma to the culture medium. Similarly, IgA
      titers recovered following the addition of exogenous rIL-5. The inhibition of IgM
      production, however, was not influenced by any of the cytokines tested. No
      significant differences were observed between experimental groups injected with
      antigen before or after 5-fluorouracil application. Our results suggest that the
      immunosuppression caused by 5-fluorouracil treatment can be abrogated by the
      addition of cytokines.

PMID- 8537086
TI  - Molecular characterization of human monoclonal antibodies specific for several
      HIV proteins: analysis of the VH3 family expression.
AB  - We have analyzed the heavy-chain variable (VH) region genes expressed by a panel
      of human monoclonal antibodies derived from an immunized volunteer, an AIDS
      patient and seropositive asymptomatic donors, and specific for HIV-1 env, pol and
      gag gene products. The third complementarity-determining regions show a high
      complexity with unconventional gene recombination events. Most of the VH genes
      utilized are also frequently encountered in other immune responses. Their
      sequences are, in general, typical of an antigen-driven immune response.
      Molecular mechanisms that generate high-affinity antibodies are then effective
      during HIV infection. Remarkably, VH3 family, which dominates the human antibody
      repertoire, is barely encountered among anti-HIV antibodies.

PMID- 8537087
TI  - A new and efficient method to generate human IgG monoclonal antibodies reactive
      to cancer cells using SCID-hu mice.
AB  - Human monoclonal antibodies (mAbs) are very useful for treatment of cancer, but
      they are difficult to obtain since immunization of humans is not a practical
      proposition at present. As an approach to circumvent this problem, we have
      simultaneously inoculated cancer tissues and regional lymph node cells obtained
      from lung cancer patients into SCID mice to allow in vivo stimulation of human
      lymphocytes against autologous cancer tissues. Human immunoglobulins, especially
      IgG, were observed in the SCID-hu sera, and some showed high reactivity to lung
      cancer cell lines. Testing of human B-lymphoblastoid cell lines obtained from
      SCID-hu spleen and thymus for antibody activity revealed 16-45% of them to be
      reactive to lung cancer cells. These percentages are high as compared with
      previous reports. Furthermore, we could establish 4 human IgG mAbs reactive to
      lung cancer cell lines. These results indicate successful stimulation of specific
      human lymphocytes in vivo, which thereby enables efficient generation of human
      monoclonal antibodies using SCID-hu mice.

PMID- 8537088
TI  - Role of nitric oxide in resistance and histopathology during experimental
      infection with Trypanosoma cruzi.
AB  - We analyzed the biological role of nitric oxide (NO) during murine Trypanosoma
      cruzi infection. Infection of mice with T. cruzi markedly increased NO synthesis.
      Administration of N-nitro-L-arginine methyl-esther (L-NAME) intraperitoneally or
      intragastrically diminished endogenous NO synthesis and resistance of mice to
      acute infection with three biologically different strains of T. cruzi. Mice
      protected against challenge with T. cruzi by transfer of T-cell-enriched
      populations from chronically infected animals, showed higher serum nitrate levels
      than controls non-transferred, or transferred, with T cells from non-immune mice.
      Administration of L-NAME abrogated transfer of resistance, suggesting NO
      participation in this process. Depletion of T cells from the transferred
      population abolished both protection and NO3- increase. On the contrary, mice
      chronically infected with T. cruzi showed no increased parasitemia or death upon
      treatment with L-NAME. The NO donor drug S-nitroso-acetyl-penicillamine was able
      to kill tissue culture or bloodstream trypomastigotes in vitro at biologically
      relevant concentrations. Conversely, NO appeared not to play a role in formation
      of inflammatory foci during T. cruzi infection, since infected mice treated with
      L-NAME showed no reduced inflammation.

PMID- 8537089
TI  - Induction of antigen-specific IgE response in murine lymphocytes by IL-10.
AB  - When murine spleen cells that had been primed with trinitrophenyl-keyhole limpet
      hemocyanin (TNP-KLH) were stimulated in vitro with the same antigen, anti-TNP
      IgE, as well as anti-TNP IgM and IgG1, was secreted into the culture medium. On
      the other hand, anti-TNP IgM and IgG1 were produced, but anti-TNP IgE secretion
      was negligible when the carrier (KLH)-primed spleen cells were cultured with the
      hapten-carrier antigen (TNP-KLH) under the same conditions. Anti-TNP Ig responses
      in the latter cultures are thought to reflect the interaction between normal TNP
      specific B cells and KLH-primed helper T cells. By using this culture system, we
      investigated the requirements of exogenous cytokines for inducing anti-TNP IgE
      response. The addition of interleukin-4 (IL-4), that is known to induce IgE
      response in LPS-stimulated murine B cells, failed to elicit anti-TNP IgE
      response. The combination of IL-4 with IL-2 and/or IL-5 was also ineffective.
      Interestingly, a significant level of anti-TNP IgE was induced when IL-10,
      another cytokine from type 2 helper T cells, was added to the culture. Although
      IL-10 enhanced the production of anti-TNP IgM and IgG1, as well as that of anti
      TNP IgE, the rate of enhancement was at least 3-fold higher in the IgE response
      than in the IgM and IgG1 responses. Simultaneous addition of IL-4, IL-5 or IL-13
      with IL-10 did not augment but rather reduced the enhancing effects of IL-10. IL
      10 did not further stimulate the spontaneous secretion of IgE from antigen-primed
      B cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537090
TI  - Presynaptic receptors involved in the modulation of release of noradrenaline from
      the sympathetic nerve terminals of the rat thymus.
AB  - In a previous study we have shown that, in response to electrical stimulation,
      there is a substantial release of noradrenaline (NA) from the sympathetic nerve
      terminals of the rat thymus which is of axonal, vesicular origin. In the present
      study neurochemical evidence was obtained that the release of NA is subject to
      presynaptic modulation. This modulation operates through stimulation of alpha 2B
      adrenoreceptors, N-nicotinic, P1-purinergic and prostaglandin E2 presynaptic
      receptors. Through these receptors the release of NA, i.e., the message from the
      central nervous system to the thymus, can be affected by endogenous ligands or
      drugs. A novel, potent and highly selective competitive antagonist of the alpha 2
      adrenoreceptor, CH-38083, significantly enhanced the release of NA, suggesting
      that its release in the thymus is under tonic inhibitory control exerted by
      endogenously released NA. Since adrenoreceptors on thymocytes involved in the
      modulation of certain thymocyte functions have recently been described, it is
      suggested that the presynaptic modulation of the release of NA in the thymus is
      involved in neuro-immune communication.

PMID- 8537091
TI  - HIV and the colonic route of entry: effect of inflammatory cytokines on the
      binding of HIV-gp120 and T cells to human enterocytes.

PMID- 8537092
TI  - Jacalin, a lectin interacting with O-linked sugars and mediating protection of
      CD4+ cells against HIV-1, binds to the external envelope glycoprotein gp120.

PMID- 8537093
TI  - Autoreactive T-cell line derived from PBMC of a rhesus macaque immunized with
      inactivated SIV vaccine.

PMID- 8537094
TI  - Anti-nuclear autoantibodies of the aged reactive against the surface of tumor but
      not normal cells.

PMID- 8537095
TI  - Macrophage colony-stimulating factor enhancement of antibody-dependent cellular
      cytotoxicity against human colon carcinoma cells.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) has been suggested to be an
      important defense mechanism against tumors. The effects of recombinant human
      macrophage colony-stimulating factor (rhM-CSF) on ADCC activity of human
      monocytes were investigated. Human peripheral monocytes were pre-incubated for 72
      h with rhM-CSF at various concentrations (50, 100, 200, 400 U/ml) and then used
      as effector cells in a 24-h 111-Indium release assay. Human carcinoma cell lines
      LS-174T, CBS, and KLE were used as targets to react with anti-carcinoma
      monoclonal antibodies (mAbs: murine D612, murine CC49, and chimeric CC49). A
      significant increase in ADCC activity was observed after monocytes were incubated
      in 100-400 U/ml of human rhM-CSF. Variation in ADCC activity of monocytes among
      donors was observed. The enhancement of ADCC activity was blocked by the addition
      of a neutralizing antibody to rhM-CSF. Less D612 mAb was required for the rhM-CSF
      treated monocytes to mediate an equivalent level of ADCC activity as compared to
      the untreated monocytes. Because of the low levels of rhM-CSF required in these
      studies to enhance ADCC, treatment of monocytes alone with comparable levels of
      rhM-CSF did not enhance antibody-independent cytotoxicity. Moreover, it is
      demonstrated here that recombinant human interleukin-4 (rhIL-4) and rhM-CSF can
      have a synergistic effect of monocyte-mediated ADCC on human tumor cells. These
      results thus indicate that rhM-CSF augments ADCC of human peripheral blood
      monocytes using mAbs to human carcinomas, suggesting a potential role for rhM-CSF
      in cancer immunotherapy.

PMID- 8537096
TI  - Further evidence for the relationship of HIV-1 gp120 V3 loops with Ig superfamily
      members: similarity with the putative CDR3 region of T-cell receptor delta
      chains.
AB  - Twenty-five V3 loops of envelope gp 120 extracted from 30 HIV-1 isolates were
      compared with T-cell receptor (TCR) subunits variable (V) portions using pairwise
      alignments of 11-residue peptides. The results indicate that, in comparison with
      random sequences, the analyzed V3 loops, unlike control (unrelated) sequences,
      display highly significant local similarity with TCR V delta (p approximately 10(
      20)). However, pattern-matching searches were performed on a much larger number
      of V3 loops (484). In particular, selective pattern TR * * * NT * K * I is shared
      by V delta from human T-cell line KT19E and 230 HIV-1 V3 loops (N-terminal
      portion). Pattern RA * YT * * * I * G is common for V delta chain isolated from T
      cell line DS6 of an immunodeficient patient and 69 V3 loops (C-terminal portion).
      The presented delta-chain portions of sequence similarity with the V3 loops
      overlap the putative complementarity-determining region (CDR3), thus possibly
      indicating functional similarity too.

PMID- 8537097
TI  - An IgE-binding TAME esterase in the urine of the mouse, Mus musculus domesticus.
AB  - Among the highly heterogeneous components of the mouse urinary protein complex
      (MUP) a hydrolase was detected which was capable of spliting the proteinase ester
      substrate TAME as well as a synthetic chromogenic tripeptide specific for tissue
      and urinary kallikreins. The binding of mouse-specific IgE antibodies from the
      serum of a highly mouse-allergic patient occurred preferentially to this
      kallikrein-like enzyme. This finding underscores the possible association of
      significant biological activities with predominant IgE-binding allergens,
      especially in view of the strongly sensitizing potential and the known messenger
      functions of the MUP proteins.

PMID- 8537098
TI  - The occurrence of natural antibodies to minimal component of bacterial cell wall
      (N-acetylglucosaminyl-N-acetylmuramyl dipeptide) in sera from healthy humans.
AB  - ELISA assay showed that sera from each of 729 healthy donors contained antibodies
      to the minimal component of bacterial cell walls, N-acetylglucosaminyl-N
      acetylmuramyl dipeptide (GMDP). Anti-GMDP antibody levels were determined for 686
      sera which were classified into 3 groups: high (17.6%), medium (68.7%), and low
      responder (13.7%). Inhibition analysis performed on representative sera showed
      that a proportion contained specific anti-GMDP antibodies reacting only with GMDP
      (i.e., GMDP interaction with anti-GMDP antibodies was inhibited by GMDP only)
      whereas the remaining sera reacted both with GMDP and with the tetrasaccharide
      (GlcNAc-MurNAc)2 (i.e., GMDP interaction with anti-GMDP antibodies in the latter
      sera was inhibited by both GMDP and the tetrasaccharide). Inhibition analysis
      indicated, moreover, that the anti-GMDP antibodies contained in high-responder
      sera had higher affinity than those present in low-responder ones: GMDP inhibited
      the GMDP + anti-GMDP antibody interaction by 88.7% in the former sera vs. 53% in
      the latter. Sera contained both IgM and IgG antibodies to GDMP, but the mean
      level of anti-GMDP IgG antibodies in the high-responder sera was 30 times higher
      than in the low-responder ones.

PMID- 8537099
TI  - Tissue-specific expression in mouse P815 mastocytoma cells of the cloned rat
      alpha-subunit gene of the high-affinity receptor for immunoglobulin E.
AB  - The high-affinity multisubunit receptor for IgE, Fc epsilon RI, is expressed in
      vivo in a tissue-specific manner, being found only on mast cells, basophils and
      epidermal Langerhans cells. The expression of the rat Fc epsilon RI alpha-subunit
      transcript has been examined here in the mouse mastocytoma cell line, P815, which
      does not express the endogenous mouse Fc epsilon RI alpha- or beta-subunit
      transcripts. These studies indicate that an exogenously introduced rat alpha
      subunit gene can be faithfully expressed in P815 cells, while no transcripts are
      produced in the mouse or rat B-lymphoid cell lines, SP2/0 and IR162,
      respectively. Therefore, in contrast to both B-cell lines, factors necessary for
      the tissue-specific expression of the alpha-subunit mRNA are present in the P815
      cell line, yielding a correctly processed mRNA transcript; nevertheless, this
      tissue-specific expression is not rigorously species specific. Although the
      mechanism responsible for these observations is unknown, these results do imply
      that a specific cis-trans element interaction occurs between this transcriptional
      unit and factors in the P815 cells that control fidelity of tissue-specific mRNA
      synthesis and processing from the Fc epsilon RI alpha-subunit gene. Consequently,
      this reconstructed rat Fc epsilon RI alpha-subunit gene contains minimally
      sufficient cis elements for tissue-specific expression of mRNA, and so, the P815
      cell line should be useful to define these requisite DNA cis elements of the
      gene, as well as the trans factors from P815 necessary for this process.

PMID- 8537101
TI  - Natural antibodies to dietary proteins: the existence of natural antibodies to
      alliinase (Alliin lyase) and mannose-specific lectin from garlic (Allium sativum)
      in human serum.
AB  - It is known that human serum contains natural antibodies to self and non-self
      proteins. We wished to determine whether normal human serum contains antibodies
      to dietary proteins that were never injected. We found that human serum contains
      antibodies to the two major proteins from cloves of garlic (Allium sativum) which
      is used as a flavorigard dietary food additive. The antibodies found were
      directed against alliinase and mannose-specific Allium sativum agglutinin (ASA).
      The antibodies were purified by affinity chromatography on their corresponding
      antigens. The purified immunoglobulins were mainly of the IgG and IgM classes and
      could be divided into two categories--specific and crossreactive. The anti
      alliinase antibodies were highly specific, while anti-ASA antibodies were
      polyreactive. Some of the possible reasons for this difference in specificity are
      suggested.

PMID- 8537100
TI  - Induction of limited growth and differentiation of early thymic precursor cells
      by thymic epithelial cell lines.
AB  - The early thymic precursor population of adult mice (low CD4 precursor) has the
      potential to produce T cells, B cells and dendritic cells if transferred into the
      appropriate inductive environment of an irradiated recipient. To assess its
      developmental potential in vitro, this population was isolated and cultured,
      alone and with various stromal cell lines. Cultured alone, these precursor cells
      all died rapidly. Co-culture with 3T3 fibroblasts gave good survival but no
      growth. Co-culture with thymic cortical epithelial cell lines induced significant
      proliferation after an initial 50% cell loss. However, the supernatant of these
      cortical epithelial cell lines caused only limited proliferation after very
      extensive cell death. Examination of the surface phenotype of the cultures on the
      cortical epithelial layer showed some changes which were compatible with very
      early steps of thymocyte development, but none of the features of more developed
      T cells were seen. A proportion of the proliferating cells developed some of the
      surface markers and morphology of dendritic cells. Immature myeloid cells also
      grew in these cultures; these appeared to derive from a small number of myeloid
      progenitors, possibly contaminants within the preparation, and their outgrowth
      required only soluble factors released by the cortical epithelial cells.

PMID- 8537102
TI  - Suppression of anaphylactic shock in sensitized guinea pigs by cytochalasin D.
AB  - A new highly effective pathogenetic therapy for anaphylactic reaction in vivo has
      been suggested. Forty-three guinea pigs, presensitized with horse serum and
      divided into two groups, were injected intracardially with 1 ml of 1.6 x 10(-4) M
      cytochalasin D and 1 ml of 1.6 x 10(-5) M cytochalasin D in DMSO solution at
      various times before being challenged with the serum. Experimental data not only
      showed that anaphylactic reaction can be suppressed in vivo by blocking
      cytoskeletal activity but also demonstrated different pharmacodynamic
      characteristics of cytochalasin D on clinical course, gravity and outcome of
      anaphylactic shock in sensitized guinea pigs, depending on the interval between
      administration of the drug and allergen.

PMID- 8537103
TI  - CD8+ type-2 T cells enhance the severity of acute herpes virus infection in mice.
AB  - The role of CD8+ suppressor T cells in acute herpes simplex virus type 1 (HSV)
      infection was investigated in mice. CD8+ CD11b+ TCR-gamma/delta + suppressor T
      cells (HSV-STC) were demonstrated in spleens of mice infected intraperitoneally
      (i.p.) with HSV. When HSV-STC from mice infected with a 10 LD50 of HSV (donors)
      were adoptively transferred to mice 3 days after being infected with a 1 LD50
      dose of HSV (recipients), the morbidity and mortality of recipients were greatly
      increased (mean survival time in days (MSD): 9.4 days; mortality, 100%) as
      compared with controls that received CD4+ T cells or a whole T-cell lysate from
      donors (MSD, > 19.6 days or > 19.1 days; mortality, 38% or 50%). The morbidity
      and mortality of mice exposed to a 1 LD50 of HSV were also increased when they
      were continuously treated with recombinant murine IL-4. However, the survival
      rate of mice exposed to a 10 LD50 of HSV increased after multiple treatments of
      these mice with anti-IL-4 monoclonal antibody. IL-4-producing cells were detected
      in a population of HSV-STC, and IL-4 was produced when these cells were cultured
      in the presence of UV-inactivated HSV in vitro. These results indicate that IL-4
      plays an important role in the progression of acute HSV infection and, through
      the production of IL-4, HSV-STC may increase the severity of the acute-phase
      infection of HSV in mice.

PMID- 8537104
TI  - Murine IgG subclass antibodies to antigens incorporated in liposomes containing
      lipid A.
AB  - The IgG subclass responses to antigens incorporated in liposomes containing lipid
      A were investigated using a synthetic malarial antigen (SPf66) and cholera toxin
      (CT). The antigen-specific IgG subclass response was determined in BALB/c mice
      immunized with either: (a) SPf66 encapsulated in liposomes containing lipid A,
      (b) CT bound to the surface of liposomes containing lipid A, or (c) both
      encapsulated SPf66 and surface-bound CT in the same liposomes. In each case the
      antibodies to SPf66, CT and lipid A demonstrated an IgG2a predominance. Liposomes
      containing lipid A not only increased the magnitude of the antibody response to
      liposomal antigens but elicited predominantly IgG2a subclass antibodies as well.

PMID- 8537105
TI  - Dot immunobinding assay as a new diagnostic test for human hydatid disease.
AB  - Bovine and human hydatid antigens collected from hepatic cysts and characterized
      by SDS-PAGE immunoblotting show similar patterns. The bovine hydatid antigen has
      been used to develop a simple and fast in vitro diagnostic assay for human
      hydatidosis. This method, named HA-DIA (hydatid antigen dot immunobinding assay),
      consists of incubation of a serum sample with a textile colloidal dye (pink) and
      a nitrocellulose stick to which the hydatid antigen has been bound. The presence
      of parasite-specific antibodies leads to dyeing of the stick reactive area, and a
      coloured spot appears. HA-DIA sensitivity and specificity have been studied in
      comparison with RAST-IgE and ELISA-IgG by testing 17 sera of patients with
      hydatid disease and 36 control sera from patients affected with other parasitic
      and non-parasitic diseases. HA-DIA showed positive results in all the patients'
      sera and in none of the control sera. Correlation with ELISA--IgG and RAST-IgE
      was significant. HA-DIA has been demonstrated to be of good predictive value,
      allowing a speedy diagnosis of hydatid disease. In view of its simplicity, not
      requiring any laboratory instruments, it is particularly suitable for large-scale
      field screening.

PMID- 8537106
TI  - The immune response to cytochrome c in BALB/c mice is delayed due to inability of
      their non-specific antigen-presenting cells to provide its immunodominant
      epitope.
AB  - The antibody response to horse cytochrome c (cyt.c) in BALB/c mice developed
      slowly and a substantial production of IgG antibodies was observed only 26-30
      days after immunization. Lymph node cells (LNC) of unimmunized mice proliferated
      weakly in response to both native cyt.c and its synthetic peptides. On day 8
      after immunization, LNC could not be stimulated with native cyt.c and peptide 92
      104. However, they did proliferate in response to cyt.c peptides 1-6, 1-13, 2-13,
      14-22, 46-56, 57-77, 61-77 and 61-69 which are closely related in horse and mouse
      cyt.c. On day 26, both native cyt.c and the peptides, including 92-104, were
      equally active in stimulating LNC proliferation. Both plastic-adherent and cyt.c
      specific cells panned from day 8 cells enhanced the response of unprimed cells to
      native cyt.c. Elimination of B cells demonstrated that primary recognition of
      cyt.c was mediated, at least partly, by non-specific antigen-presenting cells
      (APC) while later B cells of additional specificities were involved. It is
      concluded that immunization with horse cyt.c initiated an autoimmune response
      resulting in T-dependent anergy. Peptide determinants processed by non-specific
      APC stimulated corresponding autoreactive T cells. Specific B cells which
      appeared as a result of the response maturation processed successfully the
      immunodominant epitope and finally mediated proliferative and antibody responses.

PMID- 8537107
TI  - Effect of dehydroepiandrosterone on mitogen-induced lymphocyte proliferation and
      cytokine production in young and old F344 rats.
AB  - The steroid hormone intermediate, dehydroepiandrosterone (DHEA), has been
      proposed as a therapeutic agent for the treatment of immunosenescence in mouse
      model. In the present study, the in vitro effect of DHEA on mitogen-induced
      lymphocyte proliferation and cytokine production was evaluated in a rat model.
      Spleen lymphocytes were isolated from young (4-6 months) and old (24-26 months)
      F344 rats and were incubated with DHEA for 30 min. The induction of lymphocyte
      proliferation, interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) production
      by concanavalin A (Con A) was measured in a culture medium supplemented with
      either fetal calf serum (FCS) or with serum-free medium (Nutridoma-SR, N-SR). The
      induction of lymphocyte proliferation and IL-2 production by Con A decreased
      significantly with age, whereas induction of IFN-gamma increased with age.
      Treatment of lymphocytes with DHEA did not significantly alter Con A-induced
      proliferation or the production of IL-2 or IFN-gamma by spleen lymphocytes
      isolated from either young or old rats. These data indicate that in vitro DHEA
      treatment appears to have no immunomodulatory effect on the age-related changes
      in mitogen-induced proliferation or cytokine production in rat lymphocytes.

PMID- 8537108
TI  - Identification of natural resistance-associated macrophage protein in peripheral
      blood lymphocytes.
AB  - Natural resistance-associated macrophage protein gene (Nramp) was isolated from
      the gene locus Lsh/Ity/Bcg, which regulates macrophage activation for
      antimicrobial activity against intracellular pathogens. The deduced protein
      sequence encodes an integral membrane protein that has structural homology with
      known prokaryotic and eukaryotic transport systems. In the present study, a
      polyclonal antibody was raised with the synthetic peptide of the carboxy-terminal
      17 amino acids of human Nramp. The protein product of the gene is apparently
      present in human peripheral blood lymphocyte (PBL) as a 60 kD a protein
      recognized by the antibody, which is consistent with the calculated molecular
      mass. Bacterial lipopolysaccharide or interferon-gamma did not appear to
      stimulate the level of Nramp expression in PBL.

PMID- 8537109
TI  - Sequential occurrence of IgM, IgM/IgG, and gp120-IgM/IgG complement complexes on
      CD4+ lymphocytes in relation to CD4+ blood lymphocyte depletion in HIV+
      hemophilia patients: results of a 10-year study.
AB  - The concept of autoimmune mechanisms playing an integral role in the pathogenesis
      of HIV disease is rapidly gaining ground. In this study, we determined IgM and
      IgG antibodies, complement fragments and gp120 on the surface of CD4+ lymphocytes
      using double-fluorescence flow cytometry. Sequential analysis demonstrated an
      inverse relationship of autoantibodies and CD4+ lymphocyte counts in the
      peripheral blood. HIV+ patients without autoantibodies (16/104 = 15%) had the
      highest CD4+ blood cell counts (324 +/- 264/microliters; mean +/- SD). CD4+
      counts were successively lower in patients with complement-fixing IgM (243 +/-
      240/microliter), complement-fixing IgG and IgM (139 +/- 138/microliter), or gp120
      IgM/IgG complement complexes on the surface of CD4+ cells (38 +/- 45/microliter,
      P = 0.03). Individual patient profiles show that IgM autoantibodies typically are
      formed early after HIV infection and appear to deplete CD4+ lymphocytes very
      slowly, whereas complement-fixing IgG autoantibodies are generated at a later
      stage and deplete CD4+ lymphocytes more efficiently. The presence of both soluble
      gp120 and complement-fixing autoantibodies on CD4+ lymphocytes is associated with
      very low CD4+ cell counts and coincides with progression to terminal disease.
      Early during HIV infection autoantibody production is rather unstable, but it
      becomes more stable with disease progression and persists in advanced stages of
      the disease. These data suggest that autoantibody formation against CD4+
      lymphocytes is a pathogenic mechanism for CD4+ cell depletion.

PMID- 8537110
TI  - HLA-A null allele with a stop codon, HLA-A*0215N, identified in a homozygous
      state in a healthy adult.
AB  - A healthy adult having no serologically detectable HLA class I A locus antigens
      was identified. The parents of the individual are consanguineous. Results of a
      family study indicated that the individual is homozygous for the B46-Cw1-DR8.1
      haplotype, which was shown to be positively associated with A*0207 in our
      previous study. The HLA-A null individual is healthy and exhibits no apparent
      immunological abnormality. Total RNAs extracted from peripheral blood were
      converted to cDNAs. The reverse transcriptase-polymerase chain reaction (PCR)
      product, which is of the same size as the normally expressed gene, was easily
      obtained from the cDNAs with HLA-A locus-specific primers. The nucleotide
      sequence of this null allele (A*0215N) was the same as that of A*0207 except for
      a single nucleotide substitution which resulted in a stop codon in exon 4. From
      its nucleotide sequence, a truncated molecule was expected to be produced;
      however, the immunoprecipitation study failed to detect the predicted product.
      Genomic DNAs from 29 unrelated individuals who expressed only one HLA-A antigen
      with HLA-B46, were analyzed by a PCR-sequence-specific oligonucleotide method.
      None of the samples possessed this stop codon. Therefore, A*0215N is likely to be
      a rare allele generated by a single point mutation from A*0207.

PMID- 8537111
TI  - Completion of the DNA sequence determination of the Igh2 locus of the mouse: the
      5'-IA region.

PMID- 8537112
TI  - Motif of HLA-B*3503 peptide ligands.

PMID- 8537113
TI  - A new HLA-B15 allele (B*1522) found in Bari-Motilones Amerindians in Venezuela:
      comparison of its intron 2 sequence with those of B*1501 and B*3504.

PMID- 8537114
TI  - Non-standard D region usage by human TCRB sequences.

PMID- 8537115
TI  - Nonsynonymous mutations in an Fc-receptor structural gene in NZB mice.

PMID- 8537116
TI  - Nucleotide sequence of HLA-B*2706.

PMID- 8537117
TI  - Isolation and characterization of cDNA clones for Humly9: the human homologue of
      mouse Ly9.
AB  - Ly9 is a mouse cell membrane antigen found on all lymphocytes and coded for by a
      gene that maps to chromosome 1. We previously described the isolation and
      characterization of a full-length cDNA clone for mouse Ly9. Using cross-species
      hybridization we isolated cDNA clones encoding the human homologue Humly9.
      Analysis of the predicted protein sequence suggests that the extra-cellular
      portion of the Humly9 molecules is composed of four Ig-like domains: a V domain
      (V) without disulphide bonds and a truncated C2 domain (tC2) with two disulphide
      bonds, a second V domain without disulphide bonds and a second tC2 with two
      disulphide bonds, i.e., as V-tC2-V-tC2. The gene encoding Humly9 was mapped to
      chromosome 1 by analysis of human/hamster hybrids, and more specifically to the
      1q22 region by in situ hybridization. The protein sequence data support the view
      that Humly9 belongs to the immunoglobulin-superfamily subgroup which includes
      CD48, CD2, and LFA-3.

PMID- 8537118
TI  - The function of the octamer-binding site in the DRA promoter.
AB  - The octamer binding site, which is located immediately upstream of the poorly
      conserved DRA TATA sequence, is important for high levels of expression of this
      human major histocompatibility class II gene in B cells. In this study, we
      demonstrate that the substitution of the DRA TATA sequence with the TATA box from
      the adenovirus E1b promoter removes the requirement for the octamer binding site
      for high levels of expression from the DRA promoter. Since only the TATA box from
      the E1b but not the DRA promoters binds the TATA binding protein, we conclude
      that the octamer binding site helps to recruit TBP to the DRA promoter.

PMID- 8537119
TI  - Alloreactive cytotoxic T-lymphocyte-defined HLA-B7 subtypes differ in peptide
      antigen presentation.
AB  - We investigated T-cell-defined HLA-B7 subtypes using cDNA sequencing, analysis of
      bound peptides, and reactivity with a panel of alloreactive cytotoxic T
      lymphocyte (CTL) clones. Three subtypes (HLA-B*0702, HLA-B*0703, and HLA-B*0705)
      differ in nucleotide and predicted amino acid sequence. CTL reactivity and pooled
      peptide sequencing show that these three HLA-B7 subtypes bind distinct but
      overlapping sets of peptides. In particular B*0702 expresses D pocket residue Asp
      114 and binds peptides with P3 Arg, whereas B*0705 expresses D pocket residue Asn
      114 and binds peptides with P3 Ala, Leu, and Met. Consistent with different
      peptide-binding specificities, three alloreactive CTL differentiate between cells
      expressing B*0702, B*0703, and B*0705 by detecting specific peptide/HLA-B7
      complexes. In contrast, three other T-cell-defined HLA-B7 subtypes are identical
      to HLA-B*0702. The B*0702-expressing cell lines are differentiated by two of ten
      CTL clones. One CTL clone differentiates B*0702-expressing cells by their ability
      to present peptide antigen. Thus differences in peptide presentation can explain
      differential CTL recognition of cell lines expressing structurally identical and
      variant HLA-B7.

PMID- 8537121
TI  - Polymorphism in both X and Y box motifs controls level of expression of HLA-DRB1
      genes.
AB  - The HLA class II antigens of the human major histocompatibility complex play an
      important role in immune response. The quality of the immune response is
      determined not only by polymorphisms in their coding region, but also by the
      level of their cell-surface expression which affects, for example, the extent of
      T-cell activation. We have previously described allelic polymorphisms in the
      upstream regulatory regions of HLA-DRB genes, which affected DNA-protein
      interactions and resulted in significantly different promoter strengths. In the
      present study, we investigated the effect of polymorphisms in the X and Y box
      motifs on the transcriptional activity of DRB1 gene promoters in the DR1, DR51,
      and DR53 haplotype groups. We used normal, chimeric, and mutated DRB promoters
      and compared their relative abilities to initiate transcription of the CAT
      reporter gene in human B-cell lines. The results show that polymorphisms in both
      the X1 and Y box motifs play a dominant role in the promoter strength. In the gel
      mobility shift assay, we observed differential ability of nuclear proteins that
      bind to the polymorphic X1 and Y box elements. The results in the present study
      confirm earlier data in that the nucleotide variation in the X1 box affects the
      level of expression of DRB1 genes. In addition, the present data demonstrate that
      polymorphism in the Y box, which affects the inverted CCAAT sequence, also plays
      a dominant role in the transcriptional activity of DRB1 promoters.

PMID- 8537120
TI  - Identification of major histocompatibility complex genes in the guppy, Poecilia
      reticulata.
AB  - The guppy, Poecilia reticulata, a teleostean fish of the order
      Cyprinodontiformes, has been used extensively in studies of host-parasite
      interactions, courtship behavior, and mating preference, as well as in ecological
      and evolutionary genetics. A related species was among the first poikilotherm
      vertebrates to be used in the study of histocompatibility genes. All these
      studies could benefit from the identification and characterization of the guppy
      major histocompatibility complex (Mhc) genes. Here, both class I and class II
      genes of the guppy are described. The number of expressed loci, as determined by
      representation of clones in a cDNA library, sequencing, and Southern blot
      analysis, may be low in both Mhc classes: combined evidence suggests that there
      may be one expressed class II locus only and one or two expressed class I loci.
      The variability of aquaristic guppy stocks is very low: only three and two genes
      have been detected at the class I and class II loci, respectively, in the stocks
      examined. This genetic paucity is most likely the consequence of breeding
      practices employed by aquarists and commercial establishments. Limited sampling
      of wild guppy populations revealed extensive Mhc polymorphism at loci of both
      classes in nature. Comparison of guppy Mhc sequences with those of other
      vertebrates has revealed the existence of a set of insertions/deletions which can
      be used as characters in cladistic analysis to infer phylogenetic relationships
      among vertebrate taxa and the Mhc genes themselves. These indels are particularly
      frequent in the regions coding for the loops of alpha 1 and alpha 2 domains of
      class I proteins.

PMID- 8537122
TI  - Generation and reactivation of T-cell receptor A joining region pseudogenes in
      primates.
AB  - Tandemly duplicated T-cell receptor (Tcr) AJ (J alpha) segments contribute
      significantly to TCRA chain junctional region diversity in mammals. Since only
      limited data exists on TCRA diversity in nonhuman primates, we examined the TCRAJ
      regions of 37 chimpanzee and 71 rhesus macaque TCRA cDNA clones derived from
      inverse polymerase chain reaction on peripheral blood mononuclear cell cDNA of
      healthy animals. Twenty-five different TCRAJ regions were characterized in the
      chimpanzee and 36 in the rhesus macaque. Each bears a close structural
      relationship to an equivalent human TCRAJ region. Conserved amino acid motifs are
      shared between all three species. There are indications that differences between
      nonhuman primates and humans exist in the generation of TCRAJ pseudogenes. The
      nucleotide and amino acid sequences of the various characterized TCRAJ of each
      species are reported and we compare our results to the available information on
      human genomic sequences. Although we provide evidence of dynamic processes
      modifying TCRAJ segments during primate evolution, their repertoire and primary
      structure appears to be relatively conserved.

PMID- 8537123
TI  - Autoimmune diabetes-prone NOD mice express the Lyt2 alpha (Lyt2.1) and Lyt3 alpha
      (Lyt3.1) alleles of CD8.
AB  - Predisposition to Type I insulin-dependent diabetes (IDD) has a strong underlying
      genetic basis involving class II major histocompatibility complex (MHC) genes as
      well as several non-MHC genetic systems. In the non-obese diabetic (NOD) mouse, a
      model for human IDD, genes associated with the appearance of immune cell
      infiltrates in the pancreatic islets (insulitis) and/or overt IDD have been
      mapped to chromosomes 1, 3, 6, 11, and 17. A recent report has suggested that
      CD8+ lymphocytes of the NOD mouse might be deficient in the expression of the CD8
      beta molecule, a protein encoded by a gene on chromosome 6. The CD8 beta molecule
      is a T-cell surface marker, the lack of which could affect selection in the
      thymus, possibly permitting auto-reactive T-cell clones to populate the
      peripheral lymphoid tissues. For this reason, we examined the expression of the
      CD8 molecule by lymphocytes in the NOD mouse. Results indicate that the NOD mouse
      is not deficient in its transcription of detectable mRNA encoding either the CD8
      alpha or beta subunits. However, the NOD mouse expresses the Lyt2 alpha and Lyt3
      alpha alleles, suggesting that a portion of chromosome 6 centromeric to the
      diabetes-susceptibility genetic region is derived from an ancestry common to AKR
      and, like AKR, the CD8 alpha and CD8 beta 3.1 (but not CD8 beta 3.2) subunits are
      detected on the cell surface of T lymphocytes of the NOD mouse. Interestingly,
      though, the CD8 beta 3.1 molecule may not be expressed in the NOD mouse to the
      same extent as it is expressed in the AKR/J mouse, suggesting the possibility
      that the NOD mouse possesses a defect somewhere between transcription and cell
      surface expression of the CD8 beta molecule.

PMID- 8537124
TI  - Locus-specific de novo methylation down-regulates MHC class I in S49 lymphomas.

PMID- 8537125
TI  - Promoter region of mouse Tcrg genes.

PMID- 8537126
TI  - New microsatellite polymorphisms identified between C57BL/6, C57BL/10, and
      C57BL/KsJ inbred mouse strains.

PMID- 8537127
TI  - The sheep orthologue of the HLA-DOB gene.

PMID- 8537129
TI  - Sequence of the rhesus monkey T-cell receptor beta chain diversity and joining
      loci.

PMID- 8537128
TI  - Meiotic recombination at the Lmp2 hotspot tolerates minor sequence divergence
      between homologous chromosomes.

PMID- 8537130
TI  - Characterization of the expressed CIITA allele in the class II MHC
      transcriptional mutant RJ2.2.5.

PMID- 8537131
TI  - Structural repertoire in human VL pseudogenes of immunoglobulins: comparison with
      functional germline genes and amino acid sequences.

PMID- 8537132
TI  - The SMAGE gene family is expressed in post-meiotic spermatids during mouse germ
      cell differentiation.

PMID- 8537133
TI  - Antimicrobial agents for community-acquired respiratory tract infections.
AB  - Chemotherapy of community-acquired respiratory tract infections was reviewed from
      a microbiological perspective. The current worldwide spread of penicillin
      resistant Streptococcus pneumoniae and of ampicillin-resistant Haemophilus
      influenzae has required a reassessment of the antimicrobial agents being used for
      empiric therapy. In vitro data with different orally administered antibiotics
      were reviewed in order to identify any deficiencies in their spectra of activity
      against four common respiratory tract pathogens. Cefixime, cefuroxime axetil,
      cefprozil, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole were
      active against all four species other than penicillin-resistant pneumococci.

PMID- 8537134
TI  - Safety and efficacy of cefixime in treatment of respiratory tract infections in
      Germany.
AB  - From October, 1993 to August, 1994, a post-marketing surveillance study enrolled
      9,568 adults and children treated for respiratory tract infections with cefixime
      in a daily dose of 400 mg or 8 mg/kg body weight, respectively. Twice daily
      dosage was preferred with adults (60.4%) and children (54.4%). Bronchitis (45.5%)
      and otitis media (48.0%) were the most frequent indications given for cefixime
      use in adults and children, respectively. Bacterial analysis was done in 5.4% of
      adults and in 6.5% of children. With a median therapy of 6 days, cure or
      improvement was reported in 98.7% of adult patients and in 98.0% of children.
      Symptoms rapidly improved in a majority of patients. Adverse events occurred in
      1.12% of adult patients and 1.92% of children. In 96.7% of all cases the dry
      syrup was very well or well accepted by children. In conclusion, high efficacy
      and low incidence of side effects make cefixime a drug of choice for treatment of
      respiratory tract infections.

PMID- 8537135
TI  - Acute otitis media in childhood: a study of 20,532 cases.
AB  - We present a study of acute otitis media among 20,532 Spanish children during a 6
      month period from January through June 1991. The study was done by distributing a
      questionnaire to all Spanish pediatricians. Of the patients 51.7% were girls and
      48.3% boys; 68.7% of all children were younger than 5 years. The most frequent
      symptoms were otalgia or irritability, 92.7%; fever, 63.5%; otorrhea, 24.9%;
      vomiting, 21.4%; and another concomitant upper respiratory tract infection,
      65.5%. Otitis was bilateral in 45.6% of the cases. The most frequently used
      antibiotic was cefixime (38%), followed by amoxicillin-clavulanate (22.2%),
      amoxicillin (15.3%), 2nd-generation cephalosporins (13.5%) and macrolides (8.8%).
      In 11.8% of the patients, a change in the initial antibiotic therapy was required
      due to adverse effects. Resolution of symptoms occurred in 77.8% of the patients.

PMID- 8537136
TI  - Rational use of oral antibiotics for pediatric infections.
AB  - We carried out a survey in Japan to investigate compliance among children given
      oral antibiotics in an outpatient setting. The results of our survey revealed
      that, in Japan, approximately one-quarter of patients did not take their full
      course of antibiotics. Reasons for unsupervised self-discontinuation included:
      (1) the parent or guardian judged the infection to be cured; (2) the child
      refused to take the drug; and (3) the appearance of side effects. Causative
      organisms often involved in respiratory infections experienced in out-patient
      medicine include pneumococci, streptococci, staphylococci, Haemophilus
      influenzae, Moraxella (Branhamella) catarrhalis and Mycoplasma pneumoniae. The
      beta-lactams are effective against all of these bacterial species, with the
      exception of M. pneumoniae. We conducted a survey of beta-lactam antibiotics
      currently on the Japanese market and compared them to other oral antibiotics used
      to treat respiratory infections. Ease of administration, based on the incidence
      of adverse effects, particularly diarrhea, the dosage form, taste, dosage per
      administration and the number of doses required per day, are reported.

PMID- 8537137
TI  - Acute otitis media in children: a study of nasopharyngeal carriage of potential
      pathogens and therapeutic efficacy of cefixime and amoxicillin-clavulanate.
AB  - We conducted a large, multicenter, randomized, open-label study throughout France
      comparing the efficacy and safety of cefixime suspension (8 mg/kg/day, b.i.d.,
      for 10 days) versus amoxicillin-clavulanate suspension (80 mg/kg/day, t.i.d., for
      10 days) in 510 children (ages 6 to 36 months) with acute otitis media. The most
      frequent microorganisms colonizing the nasopharynx at the start of treatment were
      Streptococcus pneumoniae (51.5%), Haemophilus influenzae (45%) and Moraxella
      catarrhalis (30.2%). Rates of beta-lactamase positivity were 32.1% and 95.3% for
      H. influenzae and M. catarrhalis, respectively. Decreased susceptibility of S.
      pneumoniae to penicillin was found in 39.7% of isolates. Clinical efficacy was
      87.8% (223/254) for cefixime and 87.0% (215/247) for amoxicillin-clavulanate. At
      the 5-week follow-up visit, relapse had occurred in 15.7% (31/197) of cefixime
      treated patients and in 15.6% (32/205) of those treated with amoxicillin
      clavulanate. We conclude that these two regimens are equally effective in acute
      otitis media in children.

PMID- 8537138
TI  - 5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison
      with 10-day penicillin V therapy. Cefixime Study Group.
AB  - In an open, controlled, randomized multicenter study, 160 children suffering from
      pharyngitis and/or tonsillitis were treated with either 8 mg cefixime/kg body
      weight once daily for 5 days or 20,000 I.U. penicillin V/kg body weight t.i.d.
      for 10 days. One hundred fifty-one children were evaluable for clinical efficacy.
      In the cefixime group, 65 (86.7%) children were cured, seven (9.3%) were
      significantly improved, one (1.3%) relapsed and in two (2.7%) therapy failed. Of
      the patients treated with penicillin V, 69 (90.8%) were cured, five (6.6%)
      improved, one (1.3%) relapsed and in one (1.3%) therapy failed. Elimination of
      initial pathogens occurred in 57 (82.6%) patients treated with cefixime and in 60
      (88.2%) treated with penicillin V. At 3 to 4 weeks after the end of treatment,
      six relapses were seen in the cefixime group and eight in the penicillin V group.
      Mild-to-moderate adverse events that were possible related to the medication were
      seen in four children treated with cefixime and in five treated with penicillin
      V.

PMID- 8537140
TI  - Assessment of the use of cefixime for switch therapy.
AB  - Switch therapy, the switch from a parenteral to an oral antimicrobial agent, has
      been used successfully in the treatment of many serious infections. Several
      studies have found that significant cost savings can be achieved by switch
      therapy. Moreover, it has the further advantages of shortening hospital stay and
      reducing nosocomial bacteremia. With the exception of Staphylococcus aureus and
      penicillin-resistant Streptococcus pneumoniae, cefixime has similar in vitro
      activity to cefotaxime and ceftriaxone. It has a prolonged half-life, allowing
      for once-a-day dosing, and has excellent tissue penetration (132%). These
      characteristics support the use of cefixime for switch therapy when a susceptible
      pathogen has been identified.

PMID- 8537139
TI  - Oral cephalosporins for use in a parenteral-to-oral switch programme.
AB  - The advent of the newer cephalosporins has increased the feasibility of
      parenteral-oral switch programmes within this group of antibacterials. The choice
      of oral compound is governed by consideration of comparative data on in vitro
      activity and pharmacokinetics, with particular reference to the antibacterial
      levels achievable in relevant tissues. The establishment of strict patient
      criteria and an intensive programme of continuous education of the junior doctors
      are critical elements in the success of a switch programme. We have continuously
      audited the implementation, practice and financial results of a parenteral-to
      oral switch programme from cefotaxime to cefixime during the past 3 years.
      Results from this audit finally demonstrated a reversal in the upward trend of
      cephalosporin expenditures in 1994-95.

PMID- 8537141
TI  - XXIInd European Society for Artificial Organs (ESAO) Congress. Berlin, Germany,
      19-21 October 1995. Abstracts.

PMID- 8537142
TI  - Nitric oxide in heart muscle. Introduction.

PMID- 8537143
TI  - Modulation of coronary autoregulatory responses by endothelium-derived nitric
      oxide.
AB  - There is increasing evidence that endothelium-derived nitric oxide production is
      an important mechanism contributing to the regulation of myocardial perfusion
      during ischemia distal to a coronary stenosis. Studies in conscious chronically
      instrumented animals have extended observations in isolated arterioles to
      demonstrate that inhibiting nitric oxide synthase with L-arginine analogs
      increases the vulnerability of the myocardium to ischemia. The variable extent to
      which endothelium-dependent function is impaired in human atherosclerosis raises
      the possibility that abnormalities in resistance vessel control contribute to the
      functional significance of a fixed epicardial coronary stenosis. This may explain
      the wide variability between the physiological effects of a given coronary
      stenosis and its angiographic severity. Aggressive intervention to normalize
      endothelium-dependent vasodilation and local nitric oxide release may have
      beneficial effects on the functional significance of a coronary stenosis.

PMID- 8537144
TI  - Anatomic distribution of nitric oxide synthase in the heart.
AB  - Nitric oxide synthase is a useful maker for nitric oxide's scope. Localized by
      either NADPH-diaphorase histochemistry or immunohistochemical methods, most
      nitric oxide synthase activity in the normal heart is present in endothelium
      along the extensive network of arteries, veins and capillaries within myocardium.
      This endothelial isoform of nitric oxide synthase also exists in the endocardium
      lining the cavities. Neuronal nitric oxide synthase appears much less prominent,
      although the exact amount of this isoform in the heart is uncertain. Scattered
      nerves and ganglion cells are localized by the histochemical methods. While there
      is no inducible nitric oxide synthase in the normal heart, macrophages associated
      with repair following various forms of cardiac damage contain this isoform. For
      all nitric oxide synthases, however, species variation and variability among
      models underscore the importance of correlative studies of structure and
      function.

PMID- 8537145
TI  - The influence of endothelium-derived nitric oxide on myocardial contractile
      function.
AB  - Nitric oxide released by cardiac endothelial cells modulates myocardial
      contractile function through elevation of intracellular 3',5'-cyclic guanosine
      monophosphate (cGMP). In the absence of agonist stimulation, nitric oxide
      typically enhances myocardial relaxation and reduces diastolic tone, without
      significantly altering the rate of force or pressure development. This pattern of
      effect is observed with nitric oxide or with cGMP analogues in isolated rat
      cardiac myocytes, isolated ferret papillary muscle preparations, and isolated
      ejecting guinea-pig hearts. In human subjects studied at cardiac catheterisation,
      low-dose bicoronary infusions of sodium nitroprusside or of substance P induce
      similar effects on left ventricular systolic and diastolic function. These
      changes may benefit from cardiac filling and coronary perfusion by increasing the
      diastolic interval, reducing extravascular compressive forces and increasing the
      driving pressure for filling, e.g., during exercise. Nitric oxide may also
      modulate inotropic and chronotropic responses to beta-adrenergic stimulation.
      Under pathological conditions, overproduction of nitric oxide by an inducible
      nitric oxide synthase may be detrimental for contractile function. Dysfunction of
      the constitutive nitric oxide pathway could also contribute to pathophysiology,
      e.g., in conditions characterised by diastolic dysfunction. The paracrine nitric
      oxide pathway is likely to be an important regulator of cardiac contractile
      function, acting in concert and interacting with other regulatory pathways.

PMID- 8537146
TI  - Positive inotropic effect of nitric oxide in myocardium.
AB  - Cardiac endothelium modulates underlying cardiac muscle performance probably by
      releasing certain regulatory factors. Nitric oxide (NO), which accounts for the
      biological activity of the vascular endothelium-derived relaxing factor and
      relaxes vascular smooth muscle by elevating intracellular cyclic GMP (cGMP), may
      be involved in this cardiac modulation. Many recent studies have examined
      inotropic effects of NO utilizing NO donors and NO-synthase inhibitors, both in
      vitro and in vivo, with apparently contradictory results. We examined the
      myocardial effects of NO-releasing nitrovasodilators (sodium nitroprusside (SNP),
      SIN-1 and S-nitrosoacetyl penicillamine (SNAP)), a cGMP analogue, 8-bromo-cGMP,
      and the cGMP phosphodiesterase inhibitor zaprinast, in isolated cat papillary
      muscle. A novel concentration-dependent positive inotropic effect of SNP and SIN
      1 in muscles with damaged endocardial endothelium (EE) was observed which
      contrasted to their negative inotropic effect in muscles with intact EE. Both NO
      induced positive and negative inotropic effects were attenuated by methylene
      blue, suggesting a role for cGMP. Concentration response curves with addition of
      SNAP and 8-bromo-cGMP resulted in a biphasic inotropic response. While
      administration of low concentrations of SNAP and 8-bromo cGMP induced a positive
      inotropic effect, higher concentrations induced a negative inotropic effect.
      Administration of zaprinast caused a monophasic concentration-dependent positive
      inotropic effect. We conclude that basal release of NO and consequent modest
      (physiological?) elevation in cGMP may preserve myocardial function, while large
      (pathological?) increases would depress myocardial function.

PMID- 8537148
TI  - Effects of immunosuppressive therapy on expression of inducible nitric oxide
      synthase (iNOS) during cardiac allograft rejection.
AB  - Recent studies have indicated a role for nitric oxide (NO) in alloimmune
      responses and in allograft rejection. iNOS mRNA, protein and enzyme activity are
      induced in myocardium during cardiac allograft rejection. NO produced by iNOS is
      negatively inotropic and has the potential to be cytotoxic to cardiac myocytes.
      To investigate whether immunosuppressive agents would alter the expression of
      iNOS during cardiac allograft rejection, hearts from Wistar-Furth rats were
      transplanted into the abdomen of Lewis recipients. At day 5 allografts from
      treated and untreated animals were removed for pathological and biochemical
      examination. At day 5 the untreated allografts exhibited histological evidence of
      marked rejection (edema, infiltration with macrophages and lymphocytes, necrosis
      of cardiac muscle fibers). Abundant iNOS mRNA was apparent in Northern blots and
      iNOS enzyme activity was increased in ventricular homogenates and in cardiac
      myocytes purified from the untreated rejecting allografts. Incubation of isolated
      purified cardiac myocytes from normal rats for 24 h with cytokines known to be
      present during allograft rejection (IL-1 beta, TNF-alpha and IFN-gamma) was also
      associated with increased iNOS mRNA and enzyme activity. When Wistar-Furth to
      Lewis allografts were treated from time of transplantation with FK 506,
      cyclosporine A, dexamethasone or a combination of all three drugs, histological
      evidence of rejection and the levels of iNOS mRNA and enzyme activity in
      ventricular homogenates were reduced significantly below those observed in the
      untreated allografts. The data in a rat model indicate that immunosuppressive
      drugs reduce myocardial iNOS mRNA and enzyme activity in rejecting cardiac
      allografts. The results are consistent with the hypothesis that the alloimmune
      response and cytokine release are involved in the expression of iNOS during
      cardiac transplantation rejection.

PMID- 8537147
TI  - Comparative pharmacology of nitric oxide and nitric oxide generators on cardiac
      contractility in mammalian species.
AB  - Nitric oxide (NO) is a potent vasorelaxing agent at nanomolar concentrations. At
      low nanomolar concentrations, NO also inhibits platelet aggregation, attenuates
      leukocyte adherence to the vascular endothelium, and quenches superoxide
      radicals. At high nanomolar concentrations, NO attenuates smooth muscle cells
      growth and stimulates proliferation of vascular endothelial cells. However, even
      at micromolar concentrations, NO fails to significantly alter cardiac
      contractility in isolated rat or cat cardiac muscle. Moreover, L-arginine, even
      at millimolar concentrations, fails to exert a decrease in cardiac contractility
      significantly greater than that produced by D-arginine.

PMID- 8537149
TI  - Involvement of inducible nitric oxide synthase in the inflammatory process of
      myocardial infarction.
AB  - Inducible nitric oxide synthase (iNOS), which catalyzes the reaction of L
      arginine to L-citrulline and nitric oxide (NO), plays an important role in immune
      mediated cardiac disorders. The present report summarizes and discusses findings
      on the induction of NOS in myocardial infarction of rabbits. iNOS was
      significantly increased in infarcted myocardium 48 h after coronary artery
      ligation. The effect persisted for 14 days and declined thereafter.
      Immunohistochemical localization revealed macrophages as a major source of iNOS
      expression; iNOS expression was also present in infarcted human myocardium.
      Increased iNOS activity appeared to be related to the induction of apoptosis in
      infiltrating macrophages and cardiomyocytes. Moreover, preferential inhibition of
      iNOS by S-methylisothiourea sulfate (SMT) resulted in significant improvement of
      left ventricular performance and increased regional myocardial blood flow. These
      findings suggest that selective inhibition of iNOS activity may provide a
      therapeutic strategy in cardiac disorders such as myocardial infarction.

PMID- 8537150
TI  - Cardiomyopathy: a role for nitric oxide?
AB  - The negative inotropism, myocardial dilatation and cytotoxicity in inflammatory
      heart disorders may be due to increased generation of nitric oxide (NO) by
      immunological induction of a high output NO pathway. This short review discusses
      the initial experiments which lead to this hypothesis, and evaluates data that
      this pathway exists in animal and human cardiomyopathic disorders. It is proposed
      that manipulation of this pathway may prove to be beneficial in patients with
      these disorders.

PMID- 8537151
TI  - Nitric oxide, myocardial failure and septic shock.
AB  - Septic shock is a major cause of hospital deaths despite modern intensive
      therapy. Profound hypotension is caused by a collapse of regulatory mechanisms.
      Recent advances have established that bacterial products and the host
      inflammatory response together generate uncontrolled production of nitric oxide
      throughout the vasculature, accounting for this vasodilatation. Progressive heart
      failure is a further manifestation of established septic shock. Emerging research
      suggests that overproduction of nitric oxide within the myocardium likewise leads
      to loss of normal myocardial function. The possibility exists that exciting
      future therapies will be able to selectively inhibit the overproduction of nitric
      oxide and aid recovery from this frequently lethal condition.

PMID- 8537152
TI  - The role of nitric oxide and NO-donor agents in myocardial protection from
      surgical ischemic-reperfusion injury.
AB  - The coronary vascular endothelium is injured by ischemia-reperfusion, which may
      facilitate the pathophysiological role played by neutrophils. Hearts undergoing
      coronary artery bypass surgery or other surgical procedures requiring
      cardiopulmonary bypass and elective cardioplegia undergo repetitive episodes of
      ischemia and reperfusion, which leads to endothelial injury as well as
      contractile dysfunction and morphological injury, despite the use of
      cardioprotective cardioplegic solutions and other strategies of myocardial
      protection. In cardiac surgery, as in coronary occlusion, endothelial injury
      seems to occur upon reperfusion with unmodified blood. Blood cardioplegia does
      not prevent this surgical 'reperfusion injury', but does prevent extension of
      endothelial injury during the period of hypothermic cardioplegic arrest
      ('protected ischemia'). It is not known whether global cardioplegic ischemia in
      preoperatively injured hearts impairs the basal release of nitric oxide (NO) and
      hence obtunds this endogenous protective mechanism. However, enhancement of blood
      cardioplegia with the NO precursor, L-arginine, reduces postsurgical myocardial
      injury, suggesting that endogenous or basal release of NO participates in the
      modulation of ischemic-reperfusion injury. In addition, an NO-donor agent also
      protects the myocardium from surgical ischemic-reperfusion injury. Both
      cardioprotective strategies involve inhibition of neutrophil accumulation,
      consistent with the known inhibitory effects of NO on neutrophil adherence and
      neutrophil-mediated damage to the coronary endothelium. Therefore, NO-related
      therapy offers a new strategy to protect the myocardium, including the coronary
      endothelium, from surgically imposed ischemic-reperfusion injury.

PMID- 8537153
TI  - Topical therapy for psoriasis.

PMID- 8537154
TI  - Neuropathogenesis and neuropharmacology of psoriasis.

PMID- 8537155
TI  - Neuropeptides.

PMID- 8537156
TI  - Plasminogen activators, venous leg ulcers and reepithelialization.
AB  - BACKGROUND AND OBJECTIVE: The pathogenesis of leg ulcers due to chronic venous
      hypertension (CVH) seems to be related to perivenular fibrin-film formation due
      to decreased cutaneous fibrinolytic activity dependent on reduced release of
      tissue-type plasminogen activator that leads to tissue anoxia and ulcer
      formation. The purpose of the work is a spectrophotometric evaluation of
      urokinase (UPA) at the edge, the floor and in the periulcerous skin of leg
      ulcers. METHODS: We examined a group of 10 patients with chronic leg ulcers
      caused by CVH. The biopsies from each patient were taken: (1) from the edge of
      the ulcer; (2) from the perilesional skin and (3) from the floor of the ulcer.
      Urokinase levels were evaluated in the same areas in 10 control subjects. The UPA
      activity was determined spectrophotometrically at 405 nm. RESULTS: The results of
      our study showed that UPA is detectable in the center of the ulcer, on the edge,
      in the perilesional skin, as well as in the controls. Data are statistically
      significant. The highest levels of UPA are found at the edge of the ulcer; they
      were lower in the center and in the periulcerous skin. CONCLUSION: A
      chemoattracting effect of UPA on human keratinocytes has been documented and this
      study showed significantly higher levels of UPA at the edge and on the floor of
      the ulcers, suggesting a possible role of an UPA gradient that could promote
      mobilization of keratinocytes from the edge to the floor, thus inducing
      reepithelialization. Moreover, UPA could play some role in neoangiogenesis and
      fibroblast chemoattraction, thus contributing in various ways to wound healing.

PMID- 8537157
TI  - Age and gender differences in the impact of psoriasis on quality of life.
AB  - BACKGROUND: The impact of psoriasis upon the quality of life contributes
      significantly to the overall morbidity associated with the disease. An older age
      at onset of psoriasis and being a man have been associated previously with lower
      psychosocial morbidity. In order to further evaluate these potentially important
      mitigating factors, we examined the relation of age and gender on some aspects of
      psoriasis-related psychosocial morbidity. METHODS: Two hundred and fifteen
      consenting psoriasis patients, representing a wide range of disease severity,
      were studied. They included 110 men and 105 women, age range 19-87 years (age:
      mean +/- SD: 48.0 +/- 15.9 years); all endorsed a list of 30 items (by checking a
      "Yes" or "No") pertaining to life events related to psoriasis that they had
      experienced in the previous one month. The patients self-rated the severity of
      their psoriasis. The patients were categorized into four age groups of 18-29
      years (N = 28), 30-45 years (N = 77), 46-65 years (N = 76), and > 65 years (N =
      34), respectively, for the statistical analyses. RESULTS: No age or gender
      differences in the severity of psoriasis were observed. Patients of both sexes in
      the 18 to 29 and 30 to 45 year age groups reported more frequent (P < or = 0.05)
      problems related to both appearance/socialization and occupation/finances, in
      contrast to patients in the 46-65 and over-65-year age groups. No gender
      differences (P < or = 0.05) were observed in the frequency of items related to
      appearance and socialization; however, men reported greater work-related
      stresses. CONCLUSION: Psoriasis has a greater impact upon the quality of life of
      patients in the 18 to 45 year age range and affects the socialization of both
      sexes equally. Men face greater work-related stresses as a result of their
      psoriasis.

PMID- 8537158
TI  - The incidence of birthmarks in Israeli neonates.
AB  - BACKGROUND: Several studies have documented cutaneous findings in neonates of
      various racial groups. Our purpose was to determine the frequency of birthmarks
      in Israeli neonates of Jewish and Arabic origin. METHODS: A cohort of 1672
      newborn infants under 96 hours of age were examined for the presence of
      birthmarks. Of these 841 (50.3%) were Jewish and 831 (49.7%) were Arab. The
      Jewish group was further subdivided into various ethnic groups according to
      parental ancestry. RESULTS: Melanocytic brown lesions (Mongolian spots,
      congenital nevi, and cafe-au-lait spots), were more common in Arab infants. The
      vast majority of Jewish infants with Mongolian spots were of Asian or African
      ancestry. On the other hand, congenital melanocytic nevi were found only in
      Jewish infants of European ancestry. Vascular lesions (salmon patch and port-wine
      stain) in Arab neonates exhibited a female preponderance. CONCLUSIONS: Our data
      suggest that the prevalence of birthmarks in Israeli neonates is similar to the
      prevalence reported by others in white neonates.

PMID- 8537159
TI  - Multiple giant disseminated pyogenic granuloma in three patients burned by
      boiling milk.
AB  - BACKGROUND: Pyogenic granuloma is a common benign skin tumor. The multiple
      disseminated form of the disease is relatively rare. METHODS: We examined three
      patients who developed giant pyogenic granuloma after burns from boiling milk.
      The patients were a 1.5-year-old boy, a 5-year-old girl, and a 35-year-old woman,
      All three patients had second-degree burns over their face and trunk. RESULTS: In
      these patients, pyogenic granuloma had developed over the previously burned areas
      2-3 weeks after exposure. The general condition of the patients remained good and
      all lesions involuted spontaneously. In a 6-month follow-up period no relapse of
      the lesions was seen. CONCLUSIONS: The cause for development of multiple giant
      pyogenic granulomas after burns from milk remains unknown, but milk proteins or
      other components of milk, microorganisms, or the burn itself may be causative
      factors.

PMID- 8537160
TI  - Tricoadenoma of Nikolowski.
AB  - The patient, aged 50 years, with no relevant clinical history, complained of a
      symptomless, soft tumor of the right buttock that had been present for many
      years. On examination, it was found to be pediculate, oval, somewhat
      erythematous, firm on palpation, and with a central keratin plug. The greatest
      diameter of the lesion was 1.2 cm (Fig. 1). On surgical removal of the lesion, it
      was seen to be composed of a symmetric intradermal proliferation of cystic
      formations, uniformly distributed throughout and made up of flat, pluristratified
      epithelium with laminated keratin. There was little difference in the thickness
      of the walls of the cysts (Fig. 2). Some cysts were attached to a short tadpole
      shaped, epithelial cord and surrounded by a scanty fibroblastic stroma. No
      hairmatrix-like differentiation nor basaloid structures were seen, nor were
      atypical cells present. There was hardly any inflammatory infiltration.

PMID- 8537161
TI  - Pyoderma gangrenosum in a patient with gastric carcinoma.

PMID- 8537162
TI  - Triple cancers involving extramammary Paget's disease.

PMID- 8537163
TI  - Klippel-Trenaunay-Weber syndrome mimicking pyoderma gangrenosum.

PMID- 8537164
TI  - Finasteride inhibits 5 alpha-reductase activity in human dermal fibroblasts:
      prediction of its therapeutic application in androgen-related skin diseases.
AB  - BACKGROUND: The potential role of finasteride in treating androgen related skin
      disorders was investigated. METHODS: Pooled human dermal fibroblasts were used to
      assess the effect of finasteride on the 5 alpha-reductase activity in skin
      tissue. Vmax and Km were estimated in the presence of 0, 10, and 200 nM
      finasteride. RESULTS: Vmax values remain constant near 1.20 pmol/mg protein/h in
      the presence of increasing concentrations of finasteride; however, apparent Km
      increases from 0.27 nM at 0 nM finasteride to 0.31 nM and 0.44 nM at 10 nM and
      200 nM finasteride, respectively. This suggests that finasteride competes with
      testosterone and has a high affinity for same binding site of the 5 alpha
      reductase enzyme. Apparent Ki was estimated at 282 nM, indicating that a high
      concentration of finasteride is required to significantly suppress the enzyme
      activity. CONCLUSIONS: This study confirms that finasteride inhibits the
      conversion of testosterone to dihydrotestosterone in human reticular dermal
      fibroblasts. Finasteride may have therapeutic potential in treating skin
      disorders influenced by the action of dihydrotestosterone.

PMID- 8537165
TI  - Efficacy of dexamethasone pulse therapy in progressive systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis is a disease of unknown etiology for which no
      specific treatment is effective. Pulse therapy with corticosteroids has been
      tried for various autoimmune disorders with minimal side effects. We undertook
      this study to determine the efficacy of dexamethasone pulse therapy in
      progressive systemic sclerosis (PSS). METHODS: Five women with PSS between the
      ages 30 and 60 years, received 100 mg dexamethasone in 500 mL of 5% dextrose by
      slow intravenous infusion over 3 hours for 3 consecutive days, once a month.
      RESULTS: All patients had symptomatic and clinical improvement. The vital
      capacity improved in three and posttreatment histopathologic regression was seen
      in two patients. CONCLUSIONS: Dexamethasone pulse therapy may provide an
      additional option for treating systemic sclerosis.

PMID- 8537167
TI  - 13-cis-retinoic acid and bone density.
AB  - BACKGROUND: 13-Cis-retinoic acid has an influence on bone in patients on long
      term treatment as well as on short-term treatment. The presence of skeletal
      abnormalities after the treatment was established by roentgenologic and
      scintigraphic examinations. We wanted to know whether a 6-month course of low
      dose 13-cis-retinoic acid has a clinically important influence on bone density in
      men with severe acne. METHODS: We examined 15 men with severe acne before and
      after treatment with 13-cis-retinoic acid by dual-photon absorptiometry of the
      lumbar spine. RESULTS: The mean increase in bone density was 3.0% (95% confidence
      interval 1.3-4.5), which is normal for the period from puberty to late twenties.
      Bone density increased in 13 of our 15 patients. CONCLUSIONS: As shown by this
      highly sensitive modern densitometric method, 13-cis-retinoic acid has no
      clinically important influence on bone density in male patients with severe acne.

PMID- 8537166
TI  - Chemotherapy for AIDS-related and endemic African Kaposi's sarcoma in southern
      Africa.
AB  - BACKGROUND: Kaposi's sarcoma (KS), either in its endemic (African) form or its
      AIDS-related variant, is a common neoplastic disorder seen in Southern Africa.
      Chemotherapy has been proven to be very effective in advanced or relapsed African
      Kaposi's sarcoma, but much less so in AIDS-related, endemic KS. PATIENTS AND
      METHODS: The study consists of a retrospective analysis of the results of
      chemotherapy alone in 17 patients with African KS (AKS) and in 32 patients with
      epidemic AIDS-related KS (EKS), treated at the Johannesburg General Hospital
      between 1982 and 1992. Single agents included vinblastine, actinomycin D,
      bleomycin, and vincristine; combined regimens were largely
      doxorubicin/vincristine/bleomycin or etoposide/methotrexate. Outcome
      classifications were: complete remission (CR), partial remission (PR), and
      treatment failure (TF). RESULTS: Four of the 17 patients with AKS had CR, 10 a
      PR, and three were TF and died rapidly from their disease. The combined
      chemotherapeutic regimens produced marked symptomatic relief and even long-term
      remission in AKS. In patients with EKS, the response rate to chemotherapy was
      very low and of brief duration. No patient had a CR and debilitating side effects
      were common. CONCLUSIONS: The African type of AKS is a chemo-sensitive tumor,
      whereas the endemic type EKS, like its Western counterpart, has a dismal
      prognosis.

PMID- 8537168
TI  - Girolamo Fracastoro and syphilis.

PMID- 8537169
TI  - Johannes Arnold Meienhofer. 1929-1993.

PMID- 8537170
TI  - Hans Meienhofer. His years in New Jersey.

PMID- 8537171
TI  - Isolation and characterization of melanotropins from lamprey pituitary glands.
AB  - Three peptides containing the melanotropin-core amino-acid sequence, YXMXHFRWG,
      were isolated from the pituitary glands of a modern representative of the most
      primitive vertebrates, the sea lamprey, Petromyzon marinus. MSH-A, a
      nonadecapeptide (NPELYQMNHFRWGQPPTHF), is free at both ends. MSH-B, an
      eicosapeptide (VQESADGYRMQHFRWGQPLP), is free at the N-terminus and amidated at
      the C-terminus. They differ strikingly from gnathostome MSHs in structure. The
      third peptide, with an apparent molecular weight of 15 kDa, was tentatively
      designated lamprey ACTH, based on a structural feature: the N-terminal 22-residue
      MSH (SVSSPKYAMGHFRWGSPDKATI) is followed by four consecutive basic amino acids
      (RKRR) and a ACTH-like sequence (PVRPNTSDSPEIPDYAF--). MSH-B is 10 and 100 times
      more potent than alpha-MSH and MSH-A, respectively, in a frog skin assay in
      vitro, whereas the lamprey ACTH showed no melanotropic activity. Lamprey ACTH
      did, however, show corticotropic activity on the lamprey pronephric and
      mesonephric tissue.

PMID- 8537172
TI  - Novel microbial inhibitors of ACE. Isolation and characterization.
AB  - Two novel microbial ACE-inhibitors BAY o 6997 and BAY q 1313 were detected in the
      fermentation broths of streptomyces spec. WS 464 and spec. WS 1065, respectively.
      Both were isolated and purified by ion exchange chromatography as initial steps,
      and final purification was achieved by HPLC or additional chromatography of the
      Cu-chelate (BAY q 1313). Both inhibitors are reversibly inactivated on chelation
      with Cu2+ or Zn2+. Irreversible inactivation occurs on standing in aqueous and
      acidic solution or in ammonium hydroxide at room temperature and more rapidly on
      heating. In 4 M sodium hydroxide solutions BAY o 6997 is completely stable, and
      BAY q 1313 still remarkably stable even on longer heating to 80 degrees C. Thus,
      BAY o 6997 was alternatively and advantageously isolated after heating of its
      solution in 4 M sodium hydroxide to 37 degrees C for 2 days and subsequent
      fractional precipitation with ethanol in a relatively pure state. Total
      hydrolysis yielded His, 2-methylamino-4-amino-butyric acid and alpha-keto butyric
      acid (BAY o 6997) and pyruvic acid (BAY q 1313) respectively. The unusual
      stability of both inhibitors in sodium hydroxide solution on the one hand and
      their instability on heating and storage in aqueous or acidic solutions on the
      other hand clearly prove that the constituents are not linked by amide bonds.

PMID- 8537173
TI  - Studies on the structure and function of the carp gonadotropin alpha subunit by
      site-directed mutagenesis.
AB  - There are two genes encoding the alpha subunit of carp gonadotropin (alpha 1 and
      alpha 2 subunits). Our previous data have demonstrated that both alpha 1 and
      alpha 2 subunits expressed in insect cells are able to associate with the beta
      subunit, but only the alpha 1/beta heterodimer displays biological activity. In
      the mature protein, there are only four amino-acid residues different between the
      alpha 1 and alpha 2 subunits. In this study we used site-directed mutagenesis and
      expressed different mutant alpha subunits in insect cells to identify which
      residue might be important for biological activity of the alpha subunit. Our
      results suggested that the change of Arg-71 to Gln-71 affected the activity of
      the carp gonadotropin alpha subunit.

PMID- 8537174
TI  - D-enantiomers of 15-residue cecropin A-melittin hybrids.
AB  - The all-D enantiomers of six 15-residue hybrids of cecropin A and melittin were
      synthesized. They contained the seven N-terminal residues of cecropin A, followed
      by eight residues from the N-terminal region of melittin. They were pure and of
      the correct composition and structure. The peptides were compared with their all
      L enantiomers. The L and D isomer pairs were each exact mirror images by circular
      dichroism at several concentrations of hexafluoroisopropanol, and at 12 or 20%
      were highly helical. The L analogs were rapidly hydrolyzed by trypsin but the D
      analogs were very resistant, making them suitable candidates for orally active
      drugs. These 15-mers did not form ion channels in normal lipid bilayers made in
      decane, but those bilayers made in squalene were thinner and the peptides did
      form ion-conducting channels. The D/L pairs of peptides were very active
      antibiotics against five representative Gram-negative and Gram-positive bacteria.
      In each case the D and L isomers were essentially equally active within
      experimental error. This is interpreted to mean that the peptides do not act by
      tight interactions with chiral receptors, enzymes or lipids. The action of these
      peptides against these organisms is best explained by self-aggregation and the
      formation of ion-conducting pores across bacterial membranes.

PMID- 8537175
TI  - Structure-function relationships of des-(B26-B30)-insulin.
AB  - In order to study the role of the amino acid in position B25 and its environment
      in shortened insulins, a series of analogues was prepared with the following
      modifications: 1, Stepwise shortening of the B-chain including replacements of
      TyrB26 and ThrB27 by glycine; 2, substitutions at the carboxamide nitrogen of des
      (B26-B30)-insulin-B25-amide by apolar, polar or charged residues of various chain
      lengths; 3, replacement of PheB25 by asparagine-amide, phenylalaninol or a series
      of alkyl and aralkyl residues. Trypsin-catalyzed semisyntheses were performed
      with Boc-protected or unprotected des-octapeptide-(B23-B30)-insulin and synthetic
      peptides. Relative receptor binding and in vitro bioactivity of [AsnB25]-des-(B26
      B30)-insulin-B25-amide was 227 and 292% (on insulin), other activities ranged
      between 1 and ca. 200%. We make the following conclusions. An L-amino acid is
      essential in position B25. The B25-carbonyl and NH groups favour high binding and
      "superpotency", but are not indispensible for receptor contacts. For high
      affinity receptor interaction, the planarity at the C gamma-atom and the distance
      of B25-side-chain branching in position B25 are important, but an aromatic ring
      is not necessary.

PMID- 8537176
TI  - Peptidyl substrates containing unnatural amino acid at the P'1 position are
      potent inhibitors of prohormone convertases.
AB  - In order to study further the importance of the P'1 residue upon the activity of
      human PC1 and human furin, two important members of subtilisin/kexin family of
      enzymes, we have prepared by solid-phase Fmoc or recently introduced FastMoc
      chemistry a series of 10 peptidyl substrate analogs. The structures of these
      analogs are based upon the core sequence of pro-mPC1(83-93) namely, D-Tyr-Lys-Glu
      Arg-Ser-Lys-Arg-Xaa-Val-Gln-Lys-Asp, where D-Tyr replaces the native L-Tyr
      residue and Xaa, representing the P'1 position, corresponds to L-Ser or to
      nonproteinacous amino acids such as Tle, Sarc, MLeu, Aib, D-Tic or L-Tic. Two
      more analogs with L-Tic at P'1 position but with one amino acid less, namely P5
      Glu or P'3 Gln, and one with a Cit residue in place of Arg at P1 site of the
      dodecapeptide were also obtained. These peptides were all fully characterized by
      a combination of MS, 1H-NMR and amino acid analysis. In contrast to the Ser
      analog, which is an excellent substrate for both hPC1 and hfurin, these analogs
      displayed moderate to strong inhibition of both hPC1 and hfurin activity in a
      reversible competitive manner. They all exhibited higher potency for hfurin than
      for hPC1, with an inhibition constant (Ki) ranging from 0.8 to 10 microM and from
      1.0 to 170 microM, respectively. Incorporation of L-Tic yielded an analog with a
      two to four-fold increased inhibition of either enzymes when compared to its D
      Tic counterpart, the effect being more pronounced for hPC1 than for hfurin.
      Comparison of these data with those for the corresponding N-terminal Fmoc
      protected peptides revealed that the highly hydrophobic N-terminal Fmoc function
      occupying the P8 position can contribute positively or negatively towards
      proteinase inhibition depending on the nature of the unnatural amino acid at P'1
      and the enzyme used. Finally, none of the analogs was significantly cleaved by
      either enzyme. FTIR data on these analogs revealed some important structural
      differences between the substrate and inhibitor analogs, as there appears to be a
      conformational shift from a more beta-sheet-like structure for the substrates to
      a more alpha-helical-like structure for the inhibitors.

PMID- 8537177
TI  - Structural contribution of the A-chain loop in relaxin.
AB  - Site-directed sequential disulfide bond formation has been used to synthesize
      relaxin analogs with modifications in the A chain loop (A10-A15). In the four
      different derivatives either the amino acid residues between the cysteines (A12
      A14) were replaced or the intrachain disulfide bond (A10-A15) was eliminated. The
      substitution of the human relaxin II sequence (His-Val-Gly; A12-14) by the
      corresponding insulin sequence (Thr-Ser-Ile) or the hydrocarbon chain of omega
      aminooctanoic acid (Aoc) caused significant loss of biological activity. Similar
      observations were made when the pair of cysteines (A10-A15) was replaced by
      either alanine or serine, whereby serine disturbs more than alanine. It is
      suggested that the structural features of the A chain loop not only make
      important contributions to the active conformation of relaxin but also that the
      structural requirements of insulin and relaxin are different.

PMID- 8537178
TI  - Design and synthesis of highly selective in vitro and in vivo uterine receptor
      antagonists of oxytocin: comparisons with Atosiban.
AB  - We report the solid phase synthesis and some pharmacological properties of seven
      position two analogues (peptides 1-7) of one of our lead oxytocin antagonists,
      des-9-glycinamide[1-(beta-mercapto-beta,beta-pentamethylenepropionic+ ++ acid),2
      O-methyltyrosine,4-threonine]ornithinevasotocin(desGly+ ++-NH2, d(CH2)5
      [Tyr(Me)2,Thr4]OVT) (A). Peptides 1-7 have the following substituents at position
      two (1) D-Tyr(Me); (2) L-Tyr(Et); (3) D-Tyr(Et); (4) L-Tyr; (5) D-Tyr; (6) D-Phe
      and (7) D-Trp. These were evaluated for agonistic and antagonistic activities in
      in vitro and in vivo OT assays, in vivo vasopressor (V1a-receptor) assays and in
      vivo antidiuretic (V2-receptor) assays. None of the seven peptides exhibits
      oxytocic or vasopressor agonism. Peptides 1, 2, 4, 6 and 7 are extremely weak V2
      agonists (V2 activities range from 0.001 to 0.02 U/mg). Peptides 3 and 5 exhibit
      weak V2 antagonism (pA2 < 6.0 and < 5.5, respectively). Peptides 1-7 exhibit
      potent in vitro (no Mg2+) OT antagonism (anti-OT pA2 values range from 7.66 to
      8.03). Peptides 1 and 4-7 exhibit potent in vivo OT antagonism. Estimated in vivo
      anti-OT pA2 values range from 7.06 to 7.79 (peptides 2 and 3 were not tested).
      With anti-V1a pA2 values of 5.17-6.25 all seven peptides exhibit reduced anti-V1a
      potencies relative to the parent peptide (A) (anti-V1a pA2 = 6.46). Four of these
      peptides (4-7) exhibit striking gains in in vitro and in vivo anti-OT/anti-V1a
      selectivities compared to (A) which has an in vitro selectivity of 30 and an in
      vivo selectivity of 18. The D-Tyr2 (5), D-Trp2 (7), D-Phe2 (6) and L-Tyr2 (4)
      analogues of (A) exhibit anti-OT (in vitro)/anti-V1a selectivities = 240, 390,
      404 and 540, respectively. The L-Tyr2 (4), D-Trp2 (7), D-Phe2 (6) and D-Tyr2 (5)
      analogues exhibited anti-OT (in vivo)/anti-V1a selectivities of 72, 80, 88 and
      95, respectively. Peptides 4-7 appear to be the most selective peptide OT
      antagonists reported to date. In this regard it may be noted that they appear to
      be as or more potent and much more selective than the closely related OT
      antagonist 1-deamino[D-Tyr(Et)2,Thr4]OVT (Atosiban) which is currently undergoing
      clinical trial as a potential therapeutic agent for the prevention of premature
      labor. Atosiban (peptide 8) was resynthesized and pharmacologically evaluated in
      our laboratories. Atosiban exhibits the following antagonistic potencies. Anti-OT
      (in vitro, no Mg2+) pA2 = 7.71; anti-OT in vivo pA2 = 7.05; anti-V1a pA2 = 6.14
      and anti-V2 pA2 approximately 5.9. Its anti-OT (in vivo)/anti-V1a selectivity is
      8. Some of these antagonists may be suitable candidates for evaluation as
      potential tocolytic agents for use in the treatment of pre-term labor. They could
      also serve as useful new pharmacological tools for studies on the physiological
      roles of oxytocin. Finally, the findings presented here provide useful clues for
      the design of more potent and more selective OT antagonists.

PMID- 8537179
TI  - Pegylated peptides. IV. Enhanced biological activity of site-directed pegylated
      GRF analogs.
AB  - Conditions have been developed for the site-specific pegylation (NH2-terminus,
      side-chain and carboxy-terminus) of a potent analog of growth hormone-releasing
      factor, [Ala15]-hGRF(1-29)-NH2. These pegylated peptides were prepared by solid
      phase peptide synthesis using the Fmoc/tBu strategy, and were fully characterized
      by analytical HPLC, amino-acid analysis, 1H-NMR spectroscopy and laser desorption
      mass spectrometry. Biological activities of hGRF analogs were determined in vitro
      utilizing stimulation of growth hormone release by cultured rat pituitary cells
      as an index. GH-releasing potencies of the pegylated hGRF analogs were compared
      to a series of model analogs of [Ala15]-hGRF(1-29)-NH2 that were acetylated or
      protected as the ethylamides at the pegylation sites. It was found that
      acetylation at the NH2-terminus resulted in reduced potency, which was not
      further affected when the NH2-terminus was pegylated, regardless of the size of
      poly(ethyleneglycol) (PEG) employed (e.g. PEG2000 or PEG5000). Pegylation at Asp8
      or Lys12 decreased biological potency, a situation which was exacerbated by
      increasing the molecular weight of PEG. Pegylation at Lys21 or Asp25 did not
      significantly affect biological activity. The C-terminal model peptide,
      [Ala15,Orn(Ac)30]-hGRF(1-29)-NH2, was the most potent analog identified in this
      series (ca. 4-5-fold that of hGRF(1-44)-NH2. The COOH-terminal pegylated analogs
      retained this increased level of biological activity independent of PEG molecular
      weight. These studies demonstrate that a biologically active peptide can be
      pegylated and retain the full in vitro potency of the peptide. However, the
      biological activity is highly dependent on the site of pegylation and, in some
      cases, the molecular weight of PEG (degree of pegylation) moiety used.

PMID- 8537180
TI  - A topographical model of mu-opioid and brain somatostatin receptor selective
      ligands. NMR and molecular dynamics studies.
AB  - We have refined the 1H NMR-based conformations of the mu-opioid receptor
      selective peptides related to somatostatin of general formula Xxx-Yyy1-Cys-Zzz-D
      Trp-Lys(Orn)5-Thr-Pen-Thr8- NH2, where Xxx, Yyy, Zzz are 0, D-Phe and Tyr for 1;
      0, D-Tic and Tyr for 2; Gly, D-Tic and Tyr for 3; and 0, D-Phe and Tic for 4,
      respectively, (Kazmierski et al., J. Am. Chem. 113, 2275-2283), using a molecular
      dynamics approach. We present evidence that the NMR data are compatible with beta
      II'-, gamma- and gamma'-turns for the central tetrapeptide Tyr-D-Trp-Lys/Orn-Thr.
      Based on detailed structural and topographical considerations, we suggest that
      the mu-opioid receptor selectivity of 2 is due to a particular spatial
      arrangement of aromatic side chains of D-Tic1 and Tyr3 (7.5 A), and that the
      opioid receptor recognition domain is located in the N-terminal part of the
      peptide while the somatostatin receptor recognition domain is determined by the
      central, turn forming part of this class of cyclic peptides. A model for a mu
      opioid selective ligand has emerged from these studies that shows excellent
      structural similarities to rigid opioid alkaloids.

PMID- 8537181
TI  - Structure-activity studies on the vasoactive intestinal peptide pharmacophore. 1.
      Analogs of tyrosine.
AB  - From previous work, the primary functional groups, i.e. side chains, of the
      vasoactive intestinal peptide which are responsible for interaction with the VIP
      receptor have been identified. One of these sites, the side chain of tyrosine22
      is essential for high receptor affinity. The present work aims to examine this
      site in greater detail. Several Boc-substituted-phenylalanine derivatives were
      prepared and incorporated into VIP analogs as replacement for tyrosine22. These
      analogs, of the form Ac-[Lys12,Nle17,X22,Val26,Thr28]-VIP, were assayed as smooth
      muscle relaxants and found to be full agonists of native VIP. Most of the
      analogs, however, proved to be less potent than the parent analog by up to 300
      fold. A few analogs, all possessing electron-donating substituents, retained
      nearly full potency. Two compounds, 3-F,4-OH-Phe, 42 and 3-OCH3,4-OH-Phe, 43,
      were found to be 1.5- and 3.4-fold more potent than the parent compound, which
      equates to being 8.9- and 20-fold more potent than native VIP. Compound 43 was
      also found to be active as a bronchodilator in vivo in guinea pigs, with slightly
      over 2-fold enhanced potency and a significantly longer duration of action (> 20
      min) when compared to the parent compound (5 min). The physical characteristics
      of the various substituents and their effect on biological activity are discussed
      with a brief analysis by QSAR techniques.

PMID- 8537182
TI  - Synthesis, crystal structure and conformation in solution of four stereoisomeric
      cyclo-lanthionine derivatives.
AB  - The synthesis of the four stereoisomeric cyclo-lanthionine derivatives: [formula:
      see text] (where AlaL denotes one end of the lanthionine unit) was carried out on
      a Kaiser-oxime resin starting from orthogonally protected lanthionine units. The
      peptide ring was prepared in 79-85% yield via amide bond formation by utilizing
      the method of peptide cyclization on an oxime resin (PCOR). The crystal and
      molecular structures of the protected cyclic dipeptides have been determined by X
      ray diffraction techniques. The two cyclic lanthionine derivatives with
      chiralities of [R,S] and [S,R] crystallized in the orthorhombic space group
      P2(1)2(1)2(1) and the [R,R]- and [S,S]-cyclo-lanthionine derivatives in the
      monoclinic space group C2. The structures were solved by direct methods and
      refined to an R factor of 0.0368-0.0573. The ring amide bonds in all four
      compounds are cis, while the urethane group is trans and extended. The NMR
      spectra of the four stereoisomers in DMSO-d6 were used to determine their
      conformation in solution. The analysis of the NMR data with constrained distance
      geometry search showed the same conformational features in solution as in the
      crystalline state.

PMID- 8537183
TI  - Structures of BAY o 6997 and BAY q 1313 microbial ACE inhibitors.
AB  - BAY o 6997 and BAY q 1313 are two novel ACE inhibitors produced by Streptomyces
      WS 464 and Streptomyces WS 1065, respectively. Their structures were elucidated
      by NMR and MS analysis of the inhibitors and a substance which formed on
      decomposition of BAY o 6997 on heating in 4 M acetic acid. Both inhibitors are
      composed of the same amino acids, namely His and 2-methylamino-4-aminobutyric
      acid. The 2-amino group of His and the 4-amino group of the 2-methylamino-4
      aminobutyric acid are bridged by differently substituted ethylene moieties. As
      determined by gas chromatography on a chiral phase, both amino acids isolated
      from the total hydrolysate after derivatisation, at least in BAY o 6997, possess
      the L-configuration.

PMID- 8537185
TI  - Alkaline protease catalysis of a secondary amine to form a peptide bond.
AB  - Procedures for peptide bond formation using esters of L-amino acids as the acyl
      donor and secondary amines such as derivatives of D- or L-proline, or
      pyroglutamic acid as the nucleophile in anhydrous 2-methyl-2-propanol catalyzed
      by alcalase or subtilisin Carlsberg have been developed. Kinetic studies have
      shown that all secondary amines tested had catalytic efficiencies (kcat/km) in
      the range 84-423 min-1 M-1. Both enzymes have identical catalytic properties. The
      selectivity of the enzyme-catalyzed reaction in 2-methyl-2-propanol shows that at
      the s-1 subsite of the enzyme only L-amino acids are substrates as acyl donors,
      and at the s-1' subsite both D- and L-amino acids are substrates. Optimal
      conditions for preparing precursors of the renin inhibitors Z-Ala-Pro-OBzl, Z
      Lys(Z)-Pro-OBzl and Z-Lys(TFA)-Pro-OBzl were studied.

PMID- 8537184
TI  - Brain cathepsin B but not metalloendopeptidases degrade rAPP751 with production
      of amyloidogenic fragments. Comparison with synthetic peptides emulating beta-
      and gamma-secretase sites.
AB  - Lysosomal cathepsin B but not L degraded rAPP751 to yield C-terminal 19-25 kDa
      fragments containing beta A4, reinforcing the view that acidic proteases
      participate in endosomal-lysosomal processing to yield amyloidogenic fragments in
      situ. This mechanism is consistent with fragmentation of endogenous APPs within
      clathrin-coated vesicles (CVs) by vesicular hydrolases, with the appearance of C
      terminal amyloidogenic fragments following incubation at pH 6.5. A neutral
      endopeptidase resembling NEP 24.11 (PS-NEP) purified from detergent extracts of
      human brain degraded rAPP751; however, breakdown was not blocked robustly by
      metal chelators or phosphoramidon, suggesting the presence of an alternative
      processing enzyme. Effects of other inhibitors showed that breakdown was mediated
      by serine-protease-like component(s). A phosphoramidon-insensitive
      metalloendopeptidase (PI-NEP) partially purified from rat brain P2 using
      detergents, and resembling NEP 24.15, showed no activity towards rAPP751.
      Peptides containing putative beta- or gamma-secretase sites were synthesized for
      purposes of examining their metabolism by the brain enzymes. Those containing
      beta-secretase sites were hydrolysed at one or more sites by the four enzymes,
      but only PI- and PS-NEP acted at the Met-Asp site of Ac-Val-Lys-Met-Asp-Ala-Glu
      Phe-Arg.NH2. In the case of substrates containing the gamma-site, these two
      categories of enzymes were the only ones degrading N-Ac-Ile-Ala.NH2. These data
      imply that the brain metalloendopeptidases, while inactive towards intact
      precursors, may be involved in turnover of intermediates containing beta- or
      gamma-sites.

PMID- 8537186
TI  - Determination of disulfide bridge pattern in omega-conopeptides.
AB  - Synthetic versions of seven naturally occurring omega-conopeptides were subjected
      to structural analyses in order to determine their disulfide bridge pattern. The
      method applied in this study uses a combination of amino-acid composition and
      peptide sequence analysis of various peptide fragments generated by different
      enzymatic digestions. A temperature modification in the Edman degradation cycles
      of a protein sequencer allowed the unambiguous detection of the cleavage of
      cystine residues. The appearance of the cystine residues in particular cycles of
      the sequence analysis was characteristic of one or several of the theoretically
      possible 15 isomers. In the case of multiple choices, possible isomers were
      further eliminated by the amino-acid and sequence analysis of peptide fragments
      generated by the enzymatic digestion. All synthetic peptides, SNX-111, -157, 
      159, -183, -185, -230 and -231, were found to have the same disulfide bridge
      pattern as determined for the naturally occurring omega-conopeptide G-VI-A, i.e.
      disulfide bridges between the half-cystines 1-16, 8-20 and 15-25 (using the amino
      acid numbering of SNX-111).

PMID- 8537187
TI  - Oxygen effect in the radiolysis of proteins. IV. Myoglobin.
AB  - Radiolysis of myoglobin was carried out under air and under nitrogen in phosphate
      buffer at pH 5 and 7. The radiation products were separated by SDS-polyacrylamide
      gel electrophoresis and by HPL gel chromatography with guanidine.HCl. Under
      nitrogen the main reaction is the aggregation caused by covalent cross-links.
      Under air the radiolysis leads to peptide chain scission, which is not a random
      process, but produces specific protein fragments. The estimated molecular weights
      of these fragments gave further support to the assumption that the aminoacyl
      proline peptide group is the preferential breaking site. In contrast to
      haemoglobin, myoglobin showed nearly no radiation-induced fragmentation under
      nitrogen.

PMID- 8537188
TI  - Design, synthesis, and characterization of HIV-1 enhancer-binding polypeptides
      derived from bacteriophage 434 repressor.
AB  - We have designed and synthesized HIV-1 enhancer-binding polypeptides that were
      derived from bacteriophage 434 repressor. These peptides were 39-54 residues long
      and contained either the recognition helix or the entire helix-turn-helix motif
      of the DNA-binding domain of 434 repressor. The dissociation constant of the
      complex formed between the standard peptide (R42) and a synthetic 70-bp HIV
      enhancer DNA was ca. 10(-8) M. The specificity of the interaction of R42 with the
      two HIV enhancers was demonstrated by competitive band shift assays, stepwise
      displacement of the p50 subunit of transcription factor NF-kappa B from its two
      HIV enhancer binding sites, and DNase I footprinting; R42 seemed to protect best
      the two TTTCC sequences of the HIV enhancers against digestion by DNase I. R42
      analogues with mutated recognition helix had lower DNA binding specificity. It
      remains to be investigated whether our artificial HIV enhancer-binding
      polypeptides are active in vivo.

PMID- 8537189
TI  - Delayed macular choriocapillary circulation in age-related macular degeneration.
AB  - PURPOSE: To investigate the macular choriocapillary circulation (MCC) in eyes
      with age-related macular degeneration (ARMD) and to correlate these findings with
      the associated clinical and angiographic drusen characteristics. METHODS:
      Scanning laser ophthalmoscope fluorescein videoangiography was performed on 34
      eyes with age-related macular degeneration and eight age-matched normal
      volunteers. Drusen characteristics were assessed using the Wisconsin age-related
      maculopathy grading scale. RESULTS: A delayed macular choriocapillary circulation
      (DMCC) was defined as a macular choriocapillary filling time greater than 3
      standard deviations from the normal mean (greater than 5 seconds). Nine (26%) of
      the 34 eyes with ARMD were found to have a DMCC. After age adjustment, eyes with
      DMCC were more likely to have geographic atrophy of the retinal pigment
      epithelium (p = 0.003) or choroidal neovascularization p = 0.07) than were eyes
      with a normal MCC. Regional differences in choriocapillary filling times were
      present in the eyes with a DMCC, including nasal-to-temporal, central-to
      peripheral, and inferior-to-superior gradients of progressively less
      choriocapillary filling delay. The DMCC correlated with the location, number,
      size, confluence, and fluorescein staining characteristics of the associated
      drusen. CONCLUSION: DMCC occurs in some eyes with ARMD. This finding may not only
      assist in defining eyes at risk for progressive disease but may also help to
      elucidate the pathogenesis of age-related macular degeneration.

PMID- 8537190
TI  - Corneal endothelial permeability in protection glaucoma filter bleb with tissue
      plasminogen activator.
AB  - After glaucoma filtering surgery subconjunctival injection of human recombinant
      tissue plasminogen activator may promote the function of glaucoma filter bleb and
      increase outflow facility. It can also increase postoperative complications, such
      as corneal damage. The aim of our research was to determine corneal endothelial
      permeability (Pac) in subjects with glaucoma filter bleb protected by a
      plasminogen activator (Actilyse, Boehringer) when haemorrhagic clots obstructing
      a glaucoma filtering site had occurred. Two weeks, three months and six months
      after goniotrephining with scleral cover, in groups with and without
      subconjunctival injection of 25 mg human tissue plasminogen activator, Pac was
      calculated. In both groups, no significant differences in the level of Pac
      measured by fluorophotometry were found.

PMID- 8537191
TI  - Retinal vascular involvement in acute toxoplasmic retinochoroiditis.
AB  - The present study deals with the retinal vascular involvement in 64 patients with
      toxoplasmic retinochoroiditis during the acute phase of the disease and its
      evolution. Vascular involvement was noted in all 64 eyes during the acute phase
      of the disease. In 59 (92%) out of 64 cases the vascular involvement was located
      in the same retinal quadrant as the active toxoplasmic lesion. In the remaining 5
      eyes (8%) the vascular participation was found in all four retinal quadrants. In
      3 (5%) out of 64 cases, the vascular infiltration was extremely severe and
      resulted in retinal vascular obstruction. In all three cases the vessel traversed
      the active toxoplasmic lesion. In 35 (55%) out of 64 patients the initial
      vascular picture changed in the course of the acute phase of the disease. In
      these patients, the lesions had extended to the adjacent vessels or to other
      parts of the involved vessel. In the further course of the evolution of the
      active toxoplasmic lesion, the vascular involvement did not persist
      indiscriminately. It was noted that in 14 (22%) out of 64 cases the vascular
      lesions gradually regressed and eventually disappeared together with the active
      toxoplasmic lesion and the formation of the retinochoroidal scar. In the
      remaining 50 (78%) out of 64 cases the vascular involvement either disappeared
      after the establishment of the retinochoroidal scar in 3-12 months (29 cases) or
      remained permanently (21 cases).

PMID- 8537192
TI  - Foveal avascular zone in macular branch retinal vein occlusion.
AB  - The mean area of the foveal avascular zone (FAZ) in normal subjects was reported
      as 0.231 mm2 to 0.405 mm2, using fluorescein angiography. The FAZ enlarges in
      vaso-occlusive diseases, especially diabetic retinopathy, sickle cell
      retinopathy, talc retinopathy and branch retinal vein occlusion. In the present
      study the FAZ of 20 patients affected by macular branch retinal vein occlusion
      (MBRVO) was compared with the FAZ of 41 control subjects. The FAZ mean area was
      0.56 +/- 0.34 mm2 SD in the MBRVO group, while 0.26 +/- 0.07 mm2 SD in the
      control group, with a statistically significant difference (p < 0.001). The FAZ
      mean perimeter was 4.77 +/- 1.90 mm SD in the MBRVO group, and 2.36 +/- 0.32 mm
      SD in the control group, with a statistically significant difference (p < 0.001).
      Taking into account the MBRVO group, a statistical correlation was found between
      visual acuity impairment and FAZ enlargement (p = 0.02), but not between visual
      acuity impairment and macular edema (p = 0.41). In 14 cases (70%) secondary
      avascular microzones located in the macular sector correspondent to MBRVO were
      also evident. MBRVO causes an irregular enlargement of the FAZ which seems to
      represent the most important feature related to visual acuity impairment.

PMID- 8537193
TI  - Shiva-1: in vitro and in vivo tests of the effects of a novel, synthetic, lytic
      peptide on ocular cells.
AB  - An investigation was undertaken to determine the toxicity of an intravitreal
      injection of a novel peptide drug, Shiva-1, in rabbits. The drug, a synthetic
      peptide modeled after lytic peptides secreted by certain insects, has
      antiproliferative and antibacterial properties. Initial in vitro experiments
      showed that the drug, at a concentration of 100 microM, was toxic to both Y-79
      retinoblastoma cells and human retinal pigment epithelial cells. A wide range of
      doses (6-1200 micrograms) was injected into the rabbit vitreous in an attempt to
      determine the maximum tolerated dose. Retinal toxicity was evaluated clinically,
      by electroretinography, and by light microscopy. Some localized toxicity was
      evident at 200 micrograms; all doses of 240 micrograms and above were toxic.
      While the drug appears to exhibit a narrow range between effective and toxic
      doses, the results suggest that this and other peptides of similar design merit
      further investigation for the treatment of proliferative and infectious diseases
      of the eye.

PMID- 8537194
TI  - Pathogenesis of retinal detachment associated with morning glory disc.
AB  - Pars plana vitrectomy was performed on a six-year-old boy with complete retinal
      detachment associated with a morning glory disc of his left eye. Perfluorodecalin
      was injected to unfold the retina. During surgery, perfluorodecalin leaked
      repeatedly under the retina. This case demonstrates that a retinal hole in
      tissues lying within the optic disc anomaly provides a communication for fluid
      and perfluorodecalin between the subretinal space and vitreous cavity resulting
      in a rhegmatogenous retinal detachment in the morning glory syndrome.

PMID- 8537195
TI  - The decline of admissions for xerophthalmia at Cicendo Eye Hospital, Indonesia,
      1981-1992.
AB  - Xerophthalmia due to vitamin A deficiency is a leading cause of blindness in
      children and has been a serious problem in Indonesia. To determine whether
      progress has been made in the eradication of xerophthalmia, we assessed hospital
      admissions for xerophthalmia at Cicendo Eye Hospital, Bandung, Indonesia. The
      hospital admission registry from 1981 to 1992 was reviewed. Between January 1981
      and December 1992, there were 117 admissions for xerophthalmia, and of these, 63
      were boys and 54 were girls, with an average age of 3.9 +/- 0.3 years. Hospital
      admissions for xerophthalmia declined steeply from 1981 to 1985, with a few rare
      cases from 1985 through 1992. During the same period from 1981 through 1992,
      there were no overall changes in total hospital admissions or total pediatric
      admissions. These results suggest that xerophthalmia is becoming less common in
      Indonesia.

PMID- 8537196
TI  - Suppression of experimental proliferative vitreoretinopathy by sustained
      intraocular delivery of 5-FU.
AB  - Treatment of proliferative vitreoretinopathy (PVR) requires a multidimensional
      approach. Recent studies have focused on pharmacologic techniques to inhibit
      intraocular cell proliferation by applying antimetabolite drugs. Side effects
      associated with these drugs and difficulties in achieving effective concentration
      inside the eye make drug delivery an important and difficult part of this
      approach. We have developed a sustained-release bioerodible device with
      modifiable release properties for intraocular drug delivery. In this study, we
      evaluated the efficacy of the device with two different concentrations of 5
      fluorouracil (5-FU) in an experimental model of PVR in rabbit eyes. Both devices
      showed significant (P < 0.05) efficacy in prevention of PVR. Devices containing
      20% 5-FU (total of 1 mg) were 100% effective in prevention of tractional retinal
      detachment. No significant complications, other than mild vitreous hemorrhage in
      a few cases, were associated with this method. Because pharmacologic therapy is
      used as an augmenting method to surgical therapy, these devices can be easily
      implanted inside the eye through a sclerotomy at the completion of surgery
      without any discomfort to patients. Slow release of drug by this method reduces
      the incidence of toxicity and increases the efficacy by providing a constant
      concentration of drug during the active period of the disease.

PMID- 8537197
TI  - Short-term clinical results and complications of trabeculectomies performed with
      mitomycin C using different concentrations.
AB  - Despite the fact that trabeculectomies performed with Mitomycin C (MMC) have a
      high rate of success as repeatedly reported, the rate of complications
      encountered draws much of the attention of this substance to those cases that are
      unsatisfactory. To ascertain a possible relationship between some of these
      complications and concentrations of MMC used, we performed, in a prospective
      study, trabeculectomies for complicated cases of glaucoma with either
      concentrations of 0.5 mg/ml of MMC (group 1) or 0.2 mg/ml of MMC (group 2). The
      two groups were followed-up for 6 months and consisted of 49 and 40 cases,
      respectively. Two eyes in the first group and 3 in the second had to be
      considered as surgical failures that developed increasingly high pressures.
      Complications included hypotony most frequently (33%, both groups) with severely
      decreased vision in 3 cases (6%) of the first group and 8 (20%) in the second.
      Other results including visual acuities, IOP, and the rate of other complications
      were not significantly different in both groups and indicate that there may be no
      large difference between the two concentrations of MMC used.

PMID- 8537198
TI  - Experimental retinal tolerance to very low viscosity silicone oil (100 cs) as a
      vitreous substitute compared to higher viscosity silicone oil (5000 cs).
AB  - We evaluated the toxicity of very low viscosity (100 centistokes) and higher
      viscosity silicone oil (5000 centistokes) in rabbit eyes as a short-to-long-term
      postoperative vitreous substitute (6 weeks to 5 months). Emulsification of 100-cs
      and 5000-cs silicone oil did not occur in eyes which were followed for as long as
      5 months. No toxic effects to retinal cells were detected by light or electron
      microscopy. Because no toxic effects were seen with 100-cs silicone oil, it can
      be used in an outpatient setting as a short-term postoperative tamponading agent.
      Electroretinographic responses of silicone-injected eyes were normal.

PMID- 8537199
TI  - Regulation of GABAA receptor function and gene expression in the central nervous
      system.

PMID- 8537200
TI  - Neurotransmitter transporters: molecular biology, function, and regulation.

PMID- 8537201
TI  - Presynaptic excitability.
AB  - Based on functional characterizations with electrophysiological techniques, the
      channels in nerve terminals appear to be as diverse as channels in nerve cell
      bodies (Table I). While most presynaptic Ca2+ channels superficially resemble
      either N-type or L-type channels, variations in detail have necessitated the use
      of subscripts and other notations to indicate a nerve terminal-specific subtype
      (e.g., Wang et al., 1993). Variations such as these pose a serious obstacle to
      the identification of presynaptic channels based solely on the effects of channel
      blockers on synaptic transmission. Pharmacological sensitivity alone is not
      likely to help in determining functional properties. Crucial details, such as
      voltage sensitivity and inactivation, require direct examination. It goes without
      saying that every nerve terminal membrane contains Ca2+ channels as an entry
      pathway so that Ca2+ can trigger secretion. However, there appears to be no
      general specification of channel type, other than the exclusion of T-type Ca2+
      channels. T-type Ca2+ channels are defined functionally by strong inactivation
      and low threshold. Some presynaptic Ca2+ channels inactivate (posterior pituitary
      and Xenopus nerve terminals), and others have a somewhat reduced voltage
      threshold (retinal bipolar neurons and squid giant synapse). Perhaps it is just a
      matter of time before a nerve terminal Ca2+ channel is found with both of these
      properties. The high threshold and strong inactivation of T-type Ca2+ channels
      are thought to be adaptations for oscillations and the regulation of bursting
      activity in nerve cell bodies. The nerve terminals thus far examined have no
      endogenous electrical activity, but rather are driven by the cell body. On
      functional grounds, it is then reasonable to anticipate finding T-type Ca2+
      channels in nerve terminals that can generate electrical activity on their own.
      The rarity of such behavior in nerve terminals may be associated with the rarity
      of presynaptic T-type Ca2+ channels. In four of the five preparations reviewed in
      this chapter--motor nerve, squid giant synapse, ciliary ganglion, and retina
      bipolar neurons--evidence was presented that supports a location for Ca2+
      channels that is very close to active zones of secretion. All of these synapses
      secrete from clear vesicles, and the speed and specificity of transduction
      provided by proximity may be a common feature of these rapid synapses. In
      contrast, the posterior pituitary secretion apparatus may be triggered by higher
      affinity Ca2+ receptors and lower concentrations of Ca2+ (Lindau et al., 1992).
      This would correspond with the slower performance of peptidergic secretion, but
      because of the large stimuli needed to evoke release from neurosecretosomes, the
      possibility remains that the threshold for secretion is higher than that
      reported. While the role of Ca2+ as a trigger of secretion dictates a requirement
      for voltage-activated Ca2+ channels as universal components of the presynaptic
      membrane, the presence of other channels is more difficult to predict.
      Depolarizations caused by voltage-activated Na+ channels activate the presynaptic
      Ca2+ channels, but whether this depolarization requires Na+ channels in the
      presynaptic membrane itself may depend on the electrotonic length of the nerve
      terminal. Variations in density between motor nerve terminals may reflect species
      differences in geometry. The high Na+ channel density in the posterior pituitary
      reflects the great electrotonic length of this terminal arbor. Whether Na+
      channels are abundant or not in a presynaptic membrane, K+ channels provide the
      most robust mechanism for limiting depolarization-induced Ca2+ entry. K+ channel
      blockers enhance transmission at most synapses. In general, K+ channels are
      abundant in nerve terminals, although their apparent lower priority compared to
      Ca2+ channels in the eyes of many investigators leaves us with fewer detailed
      investigations in some preparations. Most nerve terminals have more than

PMID- 8537202
TI  - Monoamine neurotransmitters in invertebrates and vertebrates: an examination of
      the diverse enzymatic pathways utilized to synthesize and inactivate biogenic
      amines.

PMID- 8537203
TI  - Neurotransmitter systems in schizophrenia.

PMID- 8537204
TI  - Physiology of Bergmann glial cells.
AB  - While Bergmann glial cells play an important role in the development of the
      cerebellum they were thought to serve as passive insulators of the Purkinje cell
      dendritic tree and its synaptic connections. New results challenge this view and
      demonstrate that Bergmann glial cells are equipped with a large repertoire of
      receptors allowing them to sense the activity of synapses. These receptors have
      distinct biophysical and pharmacological features activating second-messenger
      pathways in the Bergmann glial cells. It is evident that the synapse has to be
      viewed as consisting of three elements, the presynaptic and postsynaptic region
      and the glial ensheathment. All three elements of this synaptic complex may
      undergo plastic changes as a prerequisite for central nervous system plasticity.
      Glial cells could interfere with synaptic transmission by communicating with
      neurons via the extracellular space, e.g., by modulating ion concentrations or
      transmitter levels in the cleft (Fig. 6).

PMID- 8537205
TI  - Genetics and the organization of the basal ganglia.

PMID- 8537206
TI  - Structure and pharmacology of vertebrate GABAA receptor subtypes.

PMID- 8537208
TI  - Chest computed tomography display preferences. Survey of thoracic radiologists.
AB  - RATIONALE AND OBJECTIVES: The authors conducted a survey of dedicated thoracic
      radiologists and tabulated their preferences for reconstruction algorithm,
      display, and photography of computed tomography (CT) scans of the chest. METHODS:
      Data were derived from a mail survey of 343 active members of the Society of
      Thoracic Radiology and based on a set of 20 questions about the display and
      photography of chest CT scans. The response rate was 35.4%. RESULTS: There were
      119 usable replies from 31 states and 8 countries. Although there was
      considerable variation, the questionnaire indicates that the "typical" dedicated
      thoracic radiologist, regardless of practice setting, uses a standard
      reconstruction algorithm for chest CT and prints images on a laser imager using
      the "sharp" setting with a 12-on-1 format. Window settings for evaluating the
      lung are window-width 1500 HU and window-level -600 HU. Window settings for
      evaluating the mediastinum are window-width 350 HU and window-level 40 HU.
      CONCLUSIONS: Although there is wide variation in the preferences used to display
      and photograph chest CT scans, most thoracic radiologists have similar display
      preferences.

PMID- 8537207
TI  - Pulmonary hypertension. Response of vasoactive peptides to a nonionic contrast
      medium in patients undergoing pulmonary angiography.
AB  - RATIONALE AND OBJECTIVES: The degree to which pulmonary angiography may
      contribute to serious complications in patients with pulmonary hypertension has
      not been clarified and remains a matter of debate. Accordingly, this study was
      designed (1) to detect the potential release of vasoactive peptides and (2) to
      investigate the hemodynamic response after administration of a nonionic contrast
      medium in patients with pulmonary hypertension undergoing pulmonary angiography.
      Allergy-mediating substances also were measured to monitor for possible
      anaphylactoid reactions. METHODS: Pulmonary digital subtraction angiography was
      performed in 20 patients with pulmonary hypertension (mean pulmonary arterial
      pressure more than 20 mm Hg). Iopromide was administered as a total of 100 mL via
      a 7F catheter inserted from the right femoral vein. The injected volume and
      duration of injection (15 to 20 mL/sec) were kept constant. Hemodynamic
      parameters were continuously monitored, including electrocardiogram, heart rate,
      phasic and mean pulmonary arterial and peripheral arterial pressures. Blood
      samples were obtained before and after administration of contrast media to assay
      for the concentration of the following vasoactive peptides using radioimmunoassay
      techniques: renin, angiotensin-I-converting enzyme, angiotensin II, aldosterone,
      atrial natriuretic peptide, antidiuretic hormone, cyclic-guanosine monophosphate,
      and myoglobin, as well as allergy-mediating substances such as tryptase,
      eosinophil protein X, and eosinophil cationic protein. RESULTS: Administration of
      iopromide caused significant increases in atrial natriuretic peptide (from 61.3
      +/- 11.8 to 94.0 +/- 16.7) and antidiuretic hormone (from 6.6 +/- 1.9 to 12.3 +/-
      3.1), whereas renin significantly decreased (from 3.0 +/- 0.6 to 1.3 +/- 0.5).
      After administration of contrast media, there were no significant changes in the
      other measured vasoactive peptides, allergy-mediating substances, and monitored
      cardiovascular parameters. CONCLUSION: Administration of iopromide for pulmonary
      angiography in patients with pulmonary hypertension resulted in no appreciable
      hemodynamic alterations associated with the observed changes in atrial
      natriuretic peptide, antidiuretic hormone, and renin. No allergy-mediated
      reactions were observed in these patients.

PMID- 8537209
TI  - Magnetic resonance imaging protocol optimization for evaluation of hyaline
      cartilage in the distal interphalangeal joint of fingers.
AB  - RATIONALE AND OBJECTIVES: To identify a single magnetic resonance imaging (MRI)
      protocol that will provide optimal signal-to-noise ratio, resolution, and image
      contrast with minimal susceptibility artifacts and that will allow clear
      delineation and visualization of cartilage, fluid, bone, tendons, and ligaments
      within the distal interphalangeal (DIP) joint of the human hand. METHODS: A
      highly optimized 2.4 T MRI system was constructed from a 31-cm horizontal bore
      magnet, using a solenoid radiofrequency coil. This was used to study the DIP
      joints of 16 healthy, asymptomatic volunteers. RESULTS: A range of image contrast
      protocols were explored, including spin-echo T1 and T2, field echo, chemical
      shift suppression to give water only images, and magnetization transfer.
      Susceptibility variations were explored by changing the field strength from 0.6
      to 2.4 T. A spin-echo protocol with TR = 1500 msec and TE = 30 msec can routinely
      produce images with resolution 0.075 x 0.150 for a slice thickness of 1 mm in 13
      minutes. That protocol can visualize simultaneously compact and trabecular bone,
      two layers of cartilage, synovial fluid, and synovium within the joint, tendons
      and ligaments, and the volar plate. CONCLUSIONS: Although the contrast is not
      fully optimized for any one tissue, the spin echo protocol (TR = 1500, TE = 30)
      provides sagittal MR images, which clearly delineate the major structures of
      interest within the DIP joint, and which will be used in future studies to
      compare changes in the DIP joint because of aging or osteoarthritis. Experience
      gained by applying the above methods to a total of 16 healthy, asymptomatic
      volunteers has enabled a single sequence to be identified, which although not
      optimized for any one tissue, nevertheless visualized simultaneously and clearly
      delineated compact and trabecular bone, two layers of cartilage, synovial fluid,
      and synovium within the joint.

PMID- 8537210
TI  - Pharmacologic treatment of intimal hyperplasia after metallic stent placement in
      the peripheral arteries. An experimental study.
AB  - RATIONALE AND OBJECTIVES: To evaluate the efficacy of oral administration of
      cilostazol, an antithrombotic agent, for the prevention of thrombotic occlusion
      and intimal hyperplasia after stenting. METHODS: Single-bodied Z-stents were
      placed in the iliac arteries of 23 dogs. Before stenting, an embolizing coil was
      introduced into the right femoral artery to reduce blood flow in the right iliac
      artery. Eleven dogs were given cilostazol orally, and the other 12 were
      unmedicated as a control group. The dogs were killed at 4, 13, and 24 weeks.
      RESULTS: Intraluminal narrowing due to thrombus was observed in 25% of dogs in
      the control group but in none of the dogs in the cilostazol group. The thickness
      of the neointima was significantly thinner in the cilostazol group than in the
      control group at 24 weeks on the noncoiled side (P < 0.05), and at 4 and 24 weeks
      on the coiled side (P < 0.01). CONCLUSIONS: These results suggest that oral
      administration of cilostazol is an effective method of preventing thrombotic
      occlusion and intimal hyperplasia after stenting.

PMID- 8537211
TI  - Safety and pharmacokinetics of iotrolan in hysterosalpingography. Retention and
      irritability compared with Lipiodol.
AB  - RATIONALE AND OBJECTIVES: The authors compared the safety and pharmacokinetics of
      Iotrolan (water-soluble) in hysterosalpingography (HSG) with those of Lipiodol
      (oil-soluble). METHODS: Iotrolan and Lipiodol were administered intraperitoneally
      at doses of 100 mg iodine/kg to female rabbits. Retention in the body was
      investigated by x-ray imaging, plasma kinetics, and urinary and fecal excretion.
      Irritability in the abdomen was investigated by histologic examination. RESULTS:
      Iotrolan was entirely excreted into the urine within 2 days after administration.
      Conversely, Lipiodol was excreted into the urine, had a half-life of 50 days, and
      was retained for more than 21 days in the abdomen. Iotrolan induced no
      inflammatory reaction in the abdomen, whereas Lipiodol induced a marked abdominal
      inflammatory reaction, including granuloma formation. Iotrolan had no effect on
      iodine concentration in the thyroid; Lipiodol increased iodine concentration
      significantly. CONCLUSIONS: Iotrolan, which is a water-soluble and nonionic
      dimeric contrast medium, has potential greater safety for use in HSG than
      Lipiodol.

PMID- 8537212
TI  - Digital subtraction shoulder arthrography in determining site and size of rotator
      cuff tear.
AB  - RATIONALE AND OBJECTIVES: To evaluate the value of digital subtraction
      arthrographic techniques in assessing the precise size and site of rotator cuff
      tear. PATIENTS AND METHODS: Prospectively interpreted findings of 29 digital
      arthrographs were compared with results after surgery in 22 patients and with
      results after arthroscopy in 7 patients. RESULTS: Surgery or arthroscopy revealed
      14 full-thickness and 2 partial-thickness tears. Digital subtraction arthrography
      showed 88% (14 of 16) of the rotator cuff tears, 86% (12 of 14) of the full
      thickness tears, and 100% (2 of 2) of the partial-thickness tears. The site of a
      tear could be shown in 86% (12 of 14), but the size was evaluated to be less
      extensive than that seen at surgery in most tears (63%, 10 of 16). CONCLUSIONS:
      The site of tears could be demonstrated in supraspinatus tendon tears, but
      measurements of the size of the tears were accurate only in small full-thickness
      and in partial-thickness tears. Very anterior and posterior tears may not be
      diagnosed with this method, and postexercise films were necessary to avoid false
      negative findings.

PMID- 8537213
TI  - The lack of immunogenicity of iotrolan.
AB  - RATIONALE AND OBJECTIVES: To test whether it would be possible to raise
      antibodies against iotrolan in rabbits and, if possible, to develop a
      radioimmunoassay for iotrolan. METHODS: A "half-molecular" analogue of iotrolan
      was synthesized, which contained a carboxylic group. This moiety was coupled via
      a link to bovine serum albumin. The resultant hapten was suspended in Freund's
      complete adjuvant and used to immunize rabbits by two subcutaneous and two
      intramuscular injections followed by monthly booster injections. After bleeding
      of the animals, the antibodies formed were tested. RESULTS: The rabbits
      successfully developed antibodies against the hapten. These antibodies were
      tested for cross-reactivity with iotrolan, the iotrolan half-molecule, and the
      hapten. Minimal cross-reactivity (below 0.5%) was found for iotrolan and the half
      molecule. Only the hapten was found to bind to the antibody. CONCLUSIONS: In the
      current test setting using a half-molecular analogue, it could be shown that
      iotrolan is probably not immunogenic. The formation of an antibody against the
      half-molecule coupled to bovine serum albumin can be explained only by
      immunogenicity of that part of the molecule, which constitutes the bridge or link
      to the albumin. This part of the hapten, however, is not representative of
      iotrolan itself.

PMID- 8537214
TI  - Quantitative analysis of computed tomography scans of the lungs for the diagnosis
      of pulmonary emphysema. A validation study of a semiautomated contour detection
      technique.
AB  - RATIONALE AND OBJECTIVES: To develop an analytic software package based on
      automated contour detection for the objective and reproducible assessment of
      emphysema from computed tomography (CT) scans. METHODS: A semiautomated technique
      was developed for the definition of lung contours in CT cross-sections followed
      by the assessment of pulmonary CT parameters describing the disease state. For 78
      images, the semiautomated contour detection was performed and compared with
      contours drawn by an experienced radiologist by calculating the systematic area
      difference (bias) and differences in pulmonary CT parameters such as the mean
      lung density (MLD). In addition, intraobserver and interobserver variabilities
      were determined in a subset of 15 images. RESULTS: The areas enclosed by the
      semiautomatically detected contours were slightly larger than the manual ones
      (bias < 2.1%). The biases in the observer studies were smaller in the
      semiautomated versus the manual case (0.3% vs. 1.3%). The standard deviation of
      the MLD differences with a manual analysis was larger by a factor of five than in
      the semiautomated case. On average, manual analysis required 2 minutes, 18
      seconds per lung; this time was reduced to 11.5 to 29 seconds with the
      semiautomated approach, depending on the respiration state. CONCLUSIONS: The
      semiautomated approach is preferred over the manual approach because of its
      higher consistency and its shorter analysis time.

PMID- 8537215
TI  - Paroxysmal choreoathetosis: an epileptic or non-epileptic disorder?
AB  - The pathophysiology of paroxysmal kinesigenic choreoathetosis (PKC) is
      controversial. Some classify it as a non-epileptic movement disorder, others
      consider PKC as a form of reflex-epilepsy but postulate that the epileptogenic
      source is within basal ganglia rather than in the cortex. An extensive invasive
      longterm monitoring in a girl with PKC demonstrated a consistent ictal discharge
      arising focally from the supplementary sensory-motor cortex (SMC), with a
      concomitant discharge recorded from the ipsilateral caudate nucleus, without
      significant spread to other neocortical areas. An hypothesis is presented to
      explain how a focal discharge within the supplementary motor cortex, demonstrated
      for the first time to occur in a patient with PKC, might cause phenomenologies
      distinct from the habitual SMC seizures and strongly suggesting a basal ganglia
      semeiology.

PMID- 8537216
TI  - So-called "petit mal status": epileptic syndrome or seizure type?
AB  - In 1945, Lennox was the first to describe the epileptic states mainly expressed
      by various degrees of consciousness disturbance, which have their onset in
      children who present epileptic absences correlated with ictal EEG patterns of
      spike-wave complex discharges at about 3 Hz. As the clinical picture seemed to be
      similar to an uninterrupted series of absences, this led to the definition "Petit
      Mal Status" (PMS). Many authors have subsequently reported that PMS can occur in
      epileptic subjects who have never presented absences (and even in subjects
      without a previous history of epilepsy) and that the related EEG pictures were
      characterised by paroxysmal generalized activity of various morphology, but
      hardly ever consisted of the continuous rhythmic spike-wave or polyspike-wave
      complexes at 3 Hz found in petit mal absences. Finally, in reporting the onset
      and recurrence of this condition typically in adults and the elderly, some
      authors have proposed the existence of a particular form of PMS (dependent on
      different types of pathologic factors and characterising a specific syndrome of
      this age) that is different from that of the "real PMS" typical of childhood and
      related to petit mal absences. This paper describes fifteen patients in whom the
      onset of the condition occurred at different ages, and who seem to exemplify the
      various possible clinical expressions of PMS, with the aim of making a
      contribution towards the better nosographic definition of this epileptic
      condition. On the basis of our study, we sustain that the so-called PMS is a
      seizure type of Idiopathic Generalized Epilepsy which may appear at nearly all
      ages, and may occur in isolation or in association with other epileptic
      manifestations, but cannot itself be considered as characterising one or more age
      dependent syndromes.

PMID- 8537217
TI  - The symptom of headache in emergency departments. The experience of a neurology
      emergency department.
AB  - Although the symptom of headache is a frequent cause of Emergency Department
      examinations, it is often considered to be of little clinical relevance in
      comparison with other emergencies and is usually treated only symptomatically.
      But how frequently does a simple headache mask a severe cerebral pathology? To
      answer this question, we studied a consecutive series of patients examined at the
      Neurology Emergency Department of Turin's Ospedale Molinette over a period of
      three months; the patients were then followed-up for more than two years in order
      to confirm the diagnoses. Of 215 cases of "acute" headache, 121 (56%) were
      essential and 94 (44%) symptomatic; of the latter, 18 (8.3%) were the only
      clinical manifestation of a severe cerebral pathology (10 hemorrhages, 2
      ischemias, 6 tumours). In diagnosing these 18 cases, 72 EEG, 57 CT and 4
      rachicentesis examinations were carried out and their diagnostic efficacy is here
      analysed. Our data show the importance of a careful evaluation of the symptom of
      headache in Emergency Departments and the need to send any doubtful cases to a
      facility specialised in coping with such emergencies.

PMID- 8537218
TI  - Magnetic resonance imaging in "typical" and "late onset" Friedreich's disease and
      early onset cerebellar ataxia with retained tendon reflexes.
AB  - MRI makes it possible to study the in vivo brain and spinal cord morphology of
      patients with hereditary ataxia. We performed T1- and T2-weighted studies in
      eleven patients with Friedreich's disease (FD), five with "late onset" FD and ten
      with early onset cerebellar ataxia with retained tendon reflexes (EOCA). Cervical
      cord atrophy was constant in FD and "late onset" FD and often associated with
      atrophy of the cerebellum and of the brainstem; T2-weighted studies showed
      posterior column degeneration in the cervical cord. The most frequent finding in
      EOCA was cerebellar atrophy, pure or associated with cervical cord or brainstem
      atrophy; the cerebellar atrophy was marked in a few cases and was related to
      disease duration.

PMID- 8537219
TI  - Anterior corpus callosotomy: effects in a patient with congenital bilateral
      perisylvian syndrome and oromotor seizures.
AB  - Anterior corpus callosotomy was performed in a patient with pseudobulbar palsy,
      mild mental retardation and intractable epilepsy related to congenital bilateral
      perisylvian cortical dysplasia. Before surgery, she had daily atonic drop
      attacks, rare and mainly sleep-related oromotor seizures, and multifocal and
      diffuse paroxysmal EEG discharges; after callosotomy, less abrupt atonic drop
      attacks recurred monthly and the EEG epileptiform abnormalities disappeared.
      Video-EEG sleep recordings revealed the clinically unsuspected serial recurrence
      of oromotor seizures, probably related to the clinically observed aggravation of
      dysarthria. New surgical techniques, in addition or alternative to callosotomy,
      should be developed in order to avoid or reduce the risk of aggravating some
      types of partial seizures in patients with bilateral cortical displastic lesions,
      intractable epilepsy and epileptic falls.

PMID- 8537220
TI  - Paroxysmal dystonia and paroxysmal tremor in a young patient with multiple
      sclerosis.
AB  - A 16-year-old patient with multiple sclerosis (MS) showed paroxysmal movement
      disorders during a recurrence of the disease. The paroxysms took the form ot
      brief unilateral dystonic posturings of the right body suggestive of paroxysmal
      dystonia (PD); they completely receded with acetazolamide. A single episode of a
      high amplitude, rythmic slow and coarse generalized tremor, present at rest and
      increasing with movement, particularly involving the head in a no-no movement,
      occurred soon after recovery from PD and lasted three hours. The present report
      provides evidence that MS has to be considered in the diagnostic approach to
      symptomatic childhood PD and underlines the efficacy of acetazolamide in the
      treatment of PD attacks. It also describes a rare paroxysmal movement disorder,
      defined as paroxysmal dystonic tremor, that can be considered as falling within
      the spectrum of PD.

PMID- 8537221
TI  - Spinal epidural abscess complicating tuberculous spondylitis.
AB  - We report the case of a patient with tuberculous L1-L2 spondylo-discitis
      complicated by a spinal epidural abscess which extended anteriorly to the cord up
      to the low cervical level. Mild signs and symptoms of spinal cord involvement
      improved with antituberculous therapy; however, after seven months of therapy,
      the MRI appearance of the abscess findings was unchanged. An attempt at surgical
      decompression and drainage of the abscess was unsuccessful because of the
      presence of dense scar tissue.

PMID- 8537222
TI  - Ethical issues in the care of patients with amyotrophic lateral sclerosis.
      Societa Italiana di Neurologia (SIN) Working Group "Bioethics and Neurology".

PMID- 8537223
TI  - Philanthropy and hospital financing.
AB  - OBJECTIVE: This study explores the relationships among donations to not-for
      profit hospitals, the returns provided by these hospitals, and fund-raising
      efforts. It tests a model of hospital behavior and addresses an earlier debate
      regarding the supply price of donations. DATA SOURCES: The main data source is
      the California Office of Statewide Health Planning data tapes of hospital
      financial disclosure reports for fiscal years 1980/1981 through 1986/1987.
      Complete data were available for 160 hospitals. STUDY DESIGN: Three structural
      equations (donations, returns, and fund-raising) are estimated as a system using
      a fixed-effects, pooled cross-section, time-series least squares regression.
      PRINCIPAL FINDINGS: Estimation results reveal the expected positive relation
      between donations and returns. The reverse relation between returns and donations
      is insignificant. The estimated effect of fund-raising on donations is
      insignificantly different from zero, and the effect of donations on fund-raising
      is negative. Fund-raising and returns are negatively associated with one another.
      CONCLUSION: The empirical results presented here suggest a positive donations
      returns relations and are consistent with a positive supply price for donations.
      Hospitals appear to view a trade-off between providing returns and soliciting
      donations, but donors do not respond equally to these two activities. Attempts to
      increase free cash flow through expansion of community returns or fund-raising
      activity, at least in the short run, are not likely to be highly successful
      financing strategies for many hospitals.

PMID- 8537224
TI  - Impact of Medicare payment reductions on access to surgical services.
AB  - OBJECTIVE: This study evaluates the impact of surgical fee reductions under
      Medicare on the utilization of surgical services. DATA SOURCES: Medicare
      physician claims data were obtained from 11 states for a five-year time period
      (1985-1989). STUDY DESIGN: Under OBRA-87, Medicare reduced payments for 11
      surgical procedures. A fixed effects regression method was used to determine the
      impact of these payment reductions on access to care for potentially vulnerable
      Medicare beneficiaries: joint Medicaid-eligibles, blacks, and the very old. DATA
      COLLECTION/EXTRACTION METHODS: Medicare claims and enrollment data were used to
      construct a cross-section time-series of population-based surgical rates from
      1985 through 1989. PRINCIPAL FINDINGS: Reductions in surgical fees led to small
      but significant increases in use for three procedures, small decreases in use for
      two procedures, and no impact on the remaining six procedures. There was little
      evidence that access to surgery was impaired for potentially vulnerable
      enrollees; in fact, declining fees often led to greater rates of increases for
      some subgroups. CONCLUSIONS: Our results suggest that volume responses by
      surgeons to payment changes under the Medicare Fee Schedule may be smaller than
      HCFA's original estimates. Nevertheless, both access and quality of care should
      continue to be closely monitored.

PMID- 8537225
TI  - Geographic variation in primary care visits in Iowa.
AB  - OBJECTIVE: This study investigates the determinants of primary care office visit
      rates. DATA SOURCES: Blue Cross and Blue Shield of Iowa subscriber information
      was sorted by residence into geographic health service areas. Cost-sharing
      information was also obtained from Blue Cross. Physician supply data were
      obtained from The University of Iowa, Office of Community-Based Programs.
      Hospital data were reported by the Iowa Hospital Association. STUDY DESIGN: Cases
      were classified into ambulatory care groups (ACGs). Use rates were computed for
      each group in each service area. Ordinary least squares regression models were
      developed to model geographic variation in each ACG-specific primary care visit
      rate. PRINCIPAL FINDINGS: Regression models were not significant for five out of
      eleven ACGs studied. Out-of-pocket expense significantly affected utilization in
      three out of six. The number of primary care practices per capita had a
      significant effect on utilization in two ACGs. The supply of hospital outpatient
      services was significant in one ACG. CONCLUSIONS: Study findings reveal that some
      ACGs are price-sensitive and some are not. Policies aimed at changing levels of
      primary care use should taken into account whether varying cost-sharing will
      influence consumer behavior in the desired direction.

PMID- 8537226
TI  - The effect of an Rx-to-OTC switch on medication prescribing patterns and
      utilization of physician services: the case of vaginal antifungal products.
AB  - OBJECTIVE: We examined the impact of over-the-counter (OTC) availability of
      vaginal antifungal products, beginning in January 1991, on medication prescribing
      patterns and utilization of physician services. DATA SOURCES AND STUDY SETTING:
      Data on utilization of health care services and prescription medications by
      female members (ages 11 and older) of the Fallon Community Health Plan (FCHP), a
      group model health maintenance organization and a component of the Fallon Health
      Care System of central Massachusetts. The census for such individuals increased
      from 49,551 in January 1990 to 67,365 in December 1992. DESIGN: Time-series
      analyses were employed to assess changes in prescribing patterns of vaginal
      antifungal products and physician visits for vaginitis from January 1, 1990
      through December 31, 1992. Monthly numbers of prescriptions for vaginal
      antifungal products and physician visits per 100 members were measured. Monetary
      savings relating to the prescription-to-OTC switch were also estimated. DATA
      COLLECTION METHODS: The computerized management information system of FCHP
      contains records on utilization of all health care services and prescriptions
      filled, collected as part of routine fiscal activities. We identified all
      vaginally administered products on the FCHP formulary used for the treatment of
      vaginal candidiasis and determined the number of prescriptions filled for these
      agents during each month of the study period. We also identified the number of
      physician office visits characterized by the ICD-9-CM code 616.10 ("vaginitis and
      vulvovaginitis, unspecified") occurring during each month of the study period.
      PRINCIPAL FINDINGS: For the one-year period after OTC availability of vaginal
      antifungal products (January 1991 through December 1991), we estimated that the
      number of prescriptions dispensed for these products was reduced by 6.42 per 100
      female FCHP members ages 11 and older. Physician visits for vaginitis were
      reduced by 0.66 per 100 members. Estimated savings to the Fallon Health Care
      System for the one-year period following OTC availability were $42,528 in
      medication costs and $12,768 to $25,729 for costs associated with physician
      visits, depending on use of laboratory testing in patient evaluations.
      CONCLUSIONS: The findings of this study suggest that the prescription-to-OTC
      switch of vaginal antifungal treatments reduced health care costs to the insurer
      in the managed care setting. These favorable effects on costs for the insurer
      need to be weighed against shifts in medication costs to consumers and potential
      adverse consequences to the patient relating to errors in self-diagnosis.

PMID- 8537227
TI  - Impact of prior and current alcohol use on use of services by patients with
      depression and chronic medical illnesses.
AB  - OBJECTIVE: Alcohol use often co-occurs with other major chronic conditions, but
      its effect on health care utilization in this context is not understood. This
      study examines the impact of alcohol consumption on health care use by patients
      with chronic medical conditions or depression, or both. DATA SOURCES/STUDY
      SETTING: Data came from the Medical Outcomes Study, an observational study of
      patients from the offices of general medical providers and mental health
      specialists in three U.S. cities. STUDY DESIGN: Longitudinal data spanning four
      years for outpatient general medical visits and outpatient mental health visits
      were analyzed using a two-part model to assess the impact of alcohol use
      disorder, problem drinking, and current and past alcohol consumption on health
      care use by patients, controlling for patient demographics and health status.
      DATA COLLECTION/EXTRACTION METHODS: Data were collected from 2,546 adult patients
      with hypertension, diabetes, heart disease (congestive heart failure or
      myocardial infarction), and/or current major depression or subthreshold
      depression using periodic, self-report surveys detailing health care utilization
      and health status information. PRINCIPAL FINDINGS: Current alcohol consumption
      increases outpatient doctor visits, and problems related to current drinking
      decrease outpatient mental health visits. CONCLUSIONS: Patterns of alcohol
      consumption have an impact on both mental health and overall health care use by
      patients with chronic medical conditions or depression.

PMID- 8537228
TI  - Expanding the frame of health services research in the drug abuse field.
AB  - OBJECTIVE: This article examines the distribution of heavy drug users across
      health and social service agencies in a community, and ways in which
      organizational and social policy factors influence pathways to services. DATA
      SOURCES/STUDY SETTING: Data are from the Community Epidemiology Laboratory, a
      project that includes comparable surveys of a wide variety of client, service
      provider, and general population groups in a single northern California county.
      STUDY DESIGN: The design is a cross-sectional analysis of patterns of service use
      and referral by heavy drug users distributed across a variety of service settings
      and in the general population. DATA COLLECTION: In-person, structured interviews
      by trained interviewers were conducted using comparable instruments, measures,
      sampling strategies, and fieldwork procedures. PRINCIPAL FINDINGS: The specialty
      drug treatment system serves only a small proportion of heavy drug users in the
      community. Large proportions of drug users are found in criminal justice, primary
      health, and welfare agencies. Patterns of service encounter and referral suggest
      that drug treatment clients typically have been in jail or on welfare prior to
      attending treatment, and are far less likely to have been referred to or from
      treatment by health providers. CONCLUSIONS: Health services research on drug
      abuse should expand its frame of reference to include services outside the
      specialty treatment sector. Drug treatment facilities are somewhat remote from
      other agencies in community service networks and are organizationally dependent
      on criminal justice and welfare systems. Further research should investigate both
      the costs and benefits of screening and providing services at earlier points of
      institutional involvement with drug abusers and the implications of
      interorganizational dependencies among criminal justice, welfare, and drug
      agencies for providers and clients.

PMID- 8537229
TI  - Advances in the prenatal and molecular diagnosis of the hemoglobinopathies and
      thalassemias.
AB  - Prenatal diagnosis is available for pregnancies at risk for virtually all
      inherited disorders of hemoglobin production. The field of reproductive genetics
      must confront many ethical, legal, and social concerns regarding its use, many of
      which derive from a woman's desire to bear children but legal right to abortion.
      The goal of more widespread utilization of prenatal diagnosis is sought in the
      context of questioning the ethical control to be exerted over the biological
      makeup of future generations. Its appropriate application would be facilitated
      greatly by the availability of reliable DNA markers of disease severity. Advances
      in fetal sampling and in detecting mutant globin genes have provided the safe,
      accurate methodology required for prenatal diagnosis. Chorionic villus sampling
      in the first trimester has become standard practice, but second trimester
      amniocentesis also is used for sampling fetal DNA. The use of preimplantation
      diagnosis and testing fetal cells from the maternal circulation will soon be
      practical. DNA-based detection of globin gene mutations has been facilitated
      greatly by the polymerase chain reaction revolution, and several reliable
      diagnostic methods are available. Polymerase chain reaction-based methods rely on
      restriction analysis, allele-specific hybridization or amplification, DNA
      sequence analysis, and new non-polymerase chain reaction methods for DNA
      amplification in vitro. These methods are available for detecting
      hemoglobinopathy, thalassemia, and thalassemic-hemoglobinopathy genes that affect
      alpha- or beta-globin loci.

PMID- 8537230
TI  - Low oxygen enhances sickle and normal erythropoiesis and fetal hemoglobin
      synthesis in vitro.
AB  - Erythropoiesis is increased in cultures of human blood progenitors when oxygen
      tension is reduced from 20% (room air) to 5% (low oxygen, closer to physiological
      bone marrow levels). The effects of low oxygen on gamma-globin synthesis and
      colony growth in methyl cellulose cultures of blood mononuclear cells from normal
      individuals and patients with sickle cell diseases were examined. Low oxygen
      increased colony numbers by 1.5- to 2-fold and erythropoietin sensitivity by
      almost 2-fold. The interval required for maximal colony growth in cultures from
      patients with sickle cell disease (sickle colonies) was reduced from 17 days in
      20% oxygen to 13 days in 5% oxygen. Relative synthesis of gamma-globin was
      examined by labeling with 3H-leucine and electrophoresis on Triton acid urea
      polyacrylamide gels. The % gamma was 1.7-fold higher in normal and 1.4-fold
      higher in sickle cultures on day 13 in low oxygen. On day 16 the expected
      temporal decline was not seen in low oxygen, and the % gamma was 2-fold higher in
      normal and 1.8-fold higher in the sickle studies. Hemin increased colony growth
      and gamma-globin synthesis in normal cultures in air, and the effects of hemin
      and low oxygen were additive. In sickle cultures, hemin and low oxygen had
      additive effects on colony growth, but only low oxygen increased gamma-globin
      synthesis. Interleukin-3 increased colony numbers on day 13, primarily by
      acceleration of peak growth. Interleukin-3 also increased gamma-globin synthesis
      in low oxygen in normal but not sickle cultures. Thus, low oxygen increases in
      vitro sensitivity to erythropoietin, colony numbers, and relative gamma-globin
      synthesis in normal and sickle cultures.

PMID- 8537231
TI  - Hb J-Wenchang-Wuming or alpha 11(A9)Lys-->Gln in an Italian woman.

PMID- 8537232
TI  - Three new neutral alpha chain variants: Hb Bois Guillaume [alpha 65(E14(Ala-
      >Val], Hb Mantes-la-Jolie [alpha 79(EF8)Ala-Thr], and Hb Mosella [alpha
      111(G18)Ala-->Thr].

PMID- 8537233
TI  - Detection of Hb J-Camaguey [alpha 141(HC3)Arg-->Gly] in three Spanish families.

PMID- 8537234
TI  - Hb S-Hb Lufkin disease in a black male infant.

PMID- 8537235
TI  - Hb A2-Agrinio [delta 43(CD2)Glu-->Gly(GAG-->GGG)]: a new delta chain variant
      detected in a Greek family.

PMID- 8537236
TI  - Beta-thalassemia intermedia in an Indian female with the Hb Hofu [beta 126(H4)Val
      ->Glu]-beta zero-thalassemia [codons 8/9 (+G)] combination.

PMID- 8537237
TI  - Identification of the -92 (C-->T) mutation by the amplification refractory
      mutation system in southern Italy.

PMID- 8537238
TI  - Patterns of the (AT)xTy motif at the -530 region 5' to the beta-globin gene in
      the Chinese population.

PMID- 8537239
TI  - Non-random distribution of spontaneous chromosome aberrations in two Bloom
      Syndrome patients.
AB  - The distribution of breakpoints involved in spontaneous chromosome aberrations
      (CA) was analyzed in lymphocytes from a family with Bloom's Syndrome (BS) and 9
      healthy individuals. Standard and G-banded metaphases from each individual were
      analyzed to allow the identification of the breakpoints involved in spontaneously
      occurring chromosome aberrations. A total of 85 breakpoints in BS patients, 17 in
      their parents and 35 in controls, could be exactly localized to specific
      chromosome bands. Breakpoint distribution was statistically analyzed considering
      the formula proposed by Brogger (1977), showing a non-random pattern in BS
      patients. Thirteen bands non-randomly involved in spontaneous CA (p < 0.005) were
      recognized in BS, located at 1p36, 1q21, 1q32, 2q33, 3p24, 3p14, 3q27, 5q31,
      6p21, 7q22, 9q13, 11q13, and 17q23. Only 1 band (1q21) was significantly
      implicated in both parents (p < 0.005), while controls showed a random
      distribution. BS non-random bands were correlated with the chromosomal location
      of fragile sites, oncogenes, and breakpoints involved in cancer rearrangements. A
      significant correlation with the location of fragile sites and cancer-breakpoints
      (p < 0.005), particularly with acute myeloid leukemia and malignant lymphomas
      rearrangements was found. These findings demonstrate that constitutional
      chromosome instability in BS might involve specific points, such as fragile sites
      and cancer breakpoints, suggesting an association with the increased incidence of
      cancer.

PMID- 8537240
TI  - A member of the mouse LRR transcript family with homology to the human Sp100
      gene.
AB  - A previously isolated cDNA sequence with homology to the long-range repeat (LRR)
      cluster in chromosome 1 of the house mouse, Mus musculus, was identified as
      derived from a 1.3 kb polyadenylated RNA. This transcript belongs to a family of
      polyadenylated RNAs which are synthesized from a multicopy gene included in the
      LRR copies. The representation of the 1.3 kb transcript in genomic DNA was
      studied in lambda and cosmid clones from the LRR cluster. Two different types of
      LRRs were detected with respect to the arrangement of coding regions. In the type
      1 arrangement, the sequence is split into five exons, and in the type-2
      arrangement, into six exons. The respective exons with their flanking regions
      were sequenced. The analysis of splice signals revealed that LRR copies with a
      type-1 arrangement are presumably the source of the 1.3 kb transcript. The 1.3 kb
      transcript has sequence homology to a human gene encoding Sp100, a nuclear
      antigen recognized by autoantibodies from patients suffering from some autoimmune
      diseases including primary biliary cirrhosis. Mouse exons II and III exhibit 71%
      homology at the nucleotide level and 56% homology at the amino acid level to the
      human Sp100 cDNA. We mapped the human Sp100 gene to chromosome 2. This location
      corroborates the assumption that the human Sp100 gene and the mouse LRR gene are
      homologous, as the human chromosome 2 contains the segment which is homologous to
      the mouse LRR region.

PMID- 8537241
TI  - Reciprocal chromosome translocation, rcp(7;17)(q26;q11), in a boar giving reduced
      litter size and increased rate of piglets dying in the early life.
AB  - Cytogenetic investigations in a boar causing a 41% reduction in litter size and
      also producing piglets that died soon after birth revealed the presence of a
      reciprocal chromosome translocation, rcp(7;17)(q26;q11). The translocation
      resulted in one extremely small telocentric chromosome marker. Synaptonemal
      complex analysis of spread spermatocytes by electron microscopy revealed an
      unusual behaviour of the translocation. This formed not only different types of
      quadrivalents (78.1% of the cells), similar to those previously found in boars
      heterozygous for reciprocal exchanges, but also completely or incompletely paired
      trivalent configurations, plus univalent (21.9%). Association between the sex
      bivalent and the translocation configuration was observed (18.7%), but testicular
      histology was normal. Furthermore, the boar with the translocation was found to
      produce tertiary monosomy and trisomy in some of the liveborn piglets. Some of
      the tertiary monosomic offspring, which died in the early extra-uterine life,
      demonstrated ventricular septal defect and cleft palate.

PMID- 8537242
TI  - Synaptonemal complex analysis in a boar with tertiary, trisomy, product of a
      rcp(7;17)(q26;q11) translocation.
AB  - Synaptonemal complex analysis by electron microscopy showed a trivalent formed by
      pairing of chromosome 17(7) with chromosome pair 7 in two zygotene cells. In 89
      pachytene cells (75.4%) the chromosome 17(7) occurred as a univalent with the
      axis being unpaired, in the shape of a ring (60.6%), a rod (38.2%) or self-paired
      (1 cell). Thirty-four (38.2%) of the univalents were paired or associated with
      the sex bivalent. Twenty-five (21.2%) of the 118 pachytene cells analysed
      demonstrated different types of trivalent pairing: the 17(7) chromosome paired
      with chromosome pair 7 in 24 cells and with pair 17 in one cell. Moreover, in 4
      cells, chromosome 17(7) was paired with both pair 7 and pair 17, forming a
      pentavalent. Trivalent association with XY was observed in 4 cells. Nineteen
      bivalents plus a univalent (8 cells), and eighteen bivalents plus a trivalent (11
      cells), were found during conventional meiotic investigation of diakinesis
      metaphase I. Though the boar demonstrated a normal testicular histology, a
      qualitatively deviant semen picture was evident.

PMID- 8537243
TI  - Localization of fragile sites in the karyotype of Felis catus.
AB  - High resolution RBG-banding was induced by exposure of cat fibroblast cultures to
      a folate antagonist and BUdR. After band induction the chromosomes displayed
      frequent breaks and gaps. To determine whether the observed aberrations were
      randomly or non-randomly distributed, a total of 300 metaphases were screened for
      the presence of breaks, gaps, and deletions. Statistical analysis was performed
      according to Mariani (1989). The 525 band idiogram presented by Ronne et al.
      (1994) was used for the calculations, and to determine which bands were
      harbouring an aberration. Bands with seven or more aberrations were considered to
      harbour a fragile site (Fh7 < 0.01).

PMID- 8537244
TI  - Heterochromatin heterogeneity revealed by restriction endonuclease digestion and
      subsequent C-banding on bovine metaphase chromosomes.
AB  - Conventional alkaline C-banding was found to be an effective additional step in
      restriction endonuclease banding to improve staining contrast and to reveal
      hidden changes in the heterochromatic blocks. Examples of these cases are
      demonstrated on the bovine chromosome set using Hinf I and Taq I endonucleases in
      the digestion experiments.

PMID- 8537245
TI  - On the epididymis and its role in the development of the fertile ejaculate.

PMID- 8537246
TI  - Human androgen insensitivity syndrome.
AB  - The clinical and pathophysiologic features of AIS provide a human model for
      understanding the role of androgen and its receptor in the induction and
      maintenance of male sex differentiation and function. Upon inspection, one is
      immediately impressed by the diverse nature of the mutations involved in the
      spectrum of AIS and the heterogeneous distribution of these mutations throughout
      the coding region of the AR gene. Because of the large number and diverse array
      of these naturally occurring mutations and their associated clinical phenotypes,
      there is great potential for understanding the structure-function relationships
      of AR from the in vitro expression of the mutant receptors in various cell lines.
      Future studies will be directed toward understanding the coordinate functional
      domains of AR, AR binding to specific androgen response elements, AR
      dimerization, AR phosphorylation, and AR interaction with accessory proteins that
      direct cell- and temporal-specific regulation of gene transactivation.

PMID- 8537247
TI  - Search for androgen response elements in the proximal promoter of the canine
      prostate arginine esterase gene.
AB  - We have demonstrated the binding of the recombinant DNA binding domain of the rat
      androgen receptor to a DNA sequence of the canine prostate arginine esterase gene
      and have determined the functional significance of this sequence in transient
      transfection experiments. One of the binding sites was localized to a region (
      172 to -148 bp) containing the sequence AGGACAACAGGTGTT that has 73% homology
      with the prostate-specific antigen (PSA) androgen response element (ARE) found at
      a similar position in the PSA promoter. Competition experiments showed that the
      androgen receptor had an approximately 100-fold more affinity for the PSA ARE
      than for the arginine sequence at -172 to -148. Transient cotransfection of 5'
      deletion mutants of the arginine esterase promoter and 5'-flanking sequences
      driving the activity of the reporter gene along with the rat androgen receptor
      expression vector yielded only negligible inductions of chloramphenicol acetyl
      transferase (CAT) activity when dihydrotestosterone (DHT) was added to the
      culture medium. The introduction of one to four repeats of the -172 to -148
      sequence of the arginine esterase gene upstream of the basal promoter of the
      mouse p12 gene in p12.108 also resulted in a minimal induction of CAT activity
      compared with a 10-fold induction of PSA AREs under similar conditions. These
      results suggest that the regulation of the canine arginine esterase gene by
      androgens is most probably achieved by mechanisms that differ from the ones
      prevailing with the human PSA and kallikrein-2 (hKLK2) genes.

PMID- 8537248
TI  - The potent relaxant effect of adenosine in rabbit corpora cavernosa is nitric
      oxide independent and mediated by A2 receptors.
AB  - In the present study the effect of adenosine and adenosine analogues on rabbit
      isolated cavernosal smooth muscle has been evaluated in comparison with the
      effect of acetylcholine and electrical field stimulation. In the presence of
      guanethidine and indomethacin, acetylcholine and electrical field stimulation
      relaxed the rabbit corpus cavernosum, which was precontracted with phenylephrine.
      The nitric oxide synthesis inhibitor, N omega-nitro-L-arginine-methylester (L
      NAME), greatly reduced the relaxation induced by electrical stimulation and
      completely abolished the relaxant effect of acetylcholine. A concentration
      dependent relaxation of the rabbit corpus cavernosum was produced by adenosine;
      this effect was not modified by L-NAME, but was reduced by adenosine deaminase.
      On the other hand, the adenosine-induced relaxation was potentiated by the
      inhibitor of adenosine deaminase, erythro-9-(2-hydroxy-3-nonyl)adenine and by the
      adenosine uptake inhibitor dipyridamole. Moreover, the effect of adenosine was
      antagonized by the unspecific adenosine receptor antagonist 8-phenyltheophylline.
      The receptor subtypes involved in cavernosal relaxation were characterized by
      using selective receptor antagonists: 1,3-dipropyl-8-cyclopentylxanthine, a
      blocker of A, receptors, did not modify adenosine-induced relaxation. This effect
      was, however, antagonized by the A2-receptor antagonist CGS15943. A relaxant
      effect was also obtained with nanomolar concentrations of two synthetic adenosine
      analogues, the preferential A2 receptor agonist 5'-N-ethylcarboxamidoadenosine
      and the A2a selective agonist CGS21680. These results demonstrated that adenosine
      has potent relaxant activity on the corpus cavernosum, acting through a mechanism
      different from the nitric oxide pathway, and that receptors involved in the
      effect of adenosine belong to the A2a subtype.

PMID- 8537249
TI  - Functional characterization of the primate sperm acrosomal antigen (PSA-63).
AB  - Monoclonal antibody (HS-63) raised in mice against human ejaculated sperm,
      polyclonal antibodies raised in rabbits against the cognate mouse testicular
      antigen (MSA-63; or Fab) and polyclonal antibodies raised in the rabbit against
      recombinant fusion proteins (GST-63) showed acrosomal localization in
      permeabilized rhesus monkey and human ejaculated sperm. Tail localization of the
      cognate primate sperm antigen (PSA-63) was also seen with intact MSA-63
      antibodies and Fab fragments. The ability of these antibodies to inhibit sperm
      binding to the zona pellucida was measured with hemizona binding assays (HZAs).
      HS-63 (1.2 mg/ml) inhibited rhesus monkey sperm binding (mean +/- SEM) to
      homologous hemizonae (treatment, 15.5 +/- 3.3; control, 58.9 +/- 9.4; P < 0.025),
      whereas comparable concentrations of protein from nonimmunized mouse preparations
      were inactive (ascites fluid, 67.6 +/- 43.5; no ascites fluid, 72.0 +/- 44.6).
      Intact MSA-63 antibodies inhibited (up to 99%) monkey sperm-zona binding in a
      concentration-dependent manner. Moreover, inhibition in this case by intact MSA
      63 antibody was limited to capacitated sperm. Similarly, intact MSA-63 antibodies
      inhibited (up to 85%) human sperm binding to homologous zonae in an antibody
      concentration-dependent manner. Fab fragments derived from MSA-63, when present
      in insemination mixtures (0.5 mg/ml), inhibited (P < 0.01) primate sperm binding
      to homologous hemizonae (monkey, 9.6 +/- 3; human sperm 9.4 +/- 2) compared with
      matched hemizona controls (monkey, 117 +/- 29; human, 20.4 +/- 3). Furthermore,
      rhesus monkey sperm-zona binding was reduced by 84% in the presence of rabbit
      anti-GST-63 antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537250
TI  - Effects of glucose and other energy substrates on the hyperactivated motility of
      macaque sperm and the zona pellucida-induced acrosome reaction.
AB  - Energy sources in sperm capacitation media have various effects on mammalian
      sperm and are required for stimulation of hyperactivated motility and/or acrosome
      reactions in some species. The present experiments were performed to investigate
      the energy substrate requirement for these two functions of macaque sperm. Semen
      from six cynomolgus macaques was washed through 60% Percoll, resuspended, and
      washed with Biggers, Whitten, and Whittingham media. In one set of experiments,
      sperm were incubated in the complete capacitation medium or in medium without
      glucose. In another set of experiments, the complete medium was used for
      comparison with medium containing no energy substrates. The absence of glucose
      did not affect survival of sperm during a 6-hour incubation period; however,
      removal of all energy substrates resulted in a decrease in percent motility by 3
      hours. Sperm were incubated for 1 hour prior to evaluation of sperm motility by
      computer-aided sperm analysis and sperm-zona binding experiments. During the last
      30 minutes of incubation, half of the aliquots of sperm suspensions were treated
      with activators (ACT; caffeine and dbcAMP, 1 mM each). As previously reported,
      when sperm were incubated in complete medium and treated with ACT there were
      changes in sperm movements that are consistent with hyperactivation. Similar or
      greater changes were observed in sperm that were incubated prior to treatment
      with ACT in glucose-free medium or in medium without any energy substrates.
      Whether sperm were incubated in complex medium or in glucose-free medium, sperm
      binding to zonae was enhanced when the sperm were treated with ACT.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8537251
TI  - Hormonal protection from cyclophosphamide-induced inactivation of rat stem
      spermatogonia.
AB  - Studies of protection of testicular function from cyclophosphamide with hormonal
      pretreatment have been limited by the lack of a convenient model for
      cyclophosphamide-induced inactivation of stem spermatogonia. In the rat, the
      mortality from cyclophosphamide had prevented the administration of sufficient
      dosages to produce detectible damage to stem spermatogonia. To overcome this
      problem, we used bone marrow transplantation and sodium 2-mercaptoethanesulfonate
      (Mesna) treatment to raise the lethal dose for 50% of the animals (LD50) for
      cyclophosphamide from 275 to > 400 mg/kg body weight. In addition we used
      irradiation, 2 weeks prior to injection of cyclophosphamide, to greatly enhance
      the measured toxicity of cyclophosphamide towards stem spermatogonia. Whereas
      sperm counts at 9 weeks after a 300 mg/kg cyclophosphamide dose were reduced by
      only a factor of 1.6 without prior irradiation, they were reduced by a factor of
      60 when 2.5 Gy of irradiation had been given. Dramatic protection against this
      toxicity was produced by hormone treatment with a gonadotropin-releasing hormone
      (GnRH) antagonist (Nal-Glu) and an antiandrogen (flutamide) following the
      radiation but prior to cyclophosphamide. This hormone treatment did not modify
      the stem cell toxicity of the radiation and it therefore must be protecting stem
      cells against cyclophosphamide-induced damage. Because GnRH antagonist
      antiandrogen treatment can protect stem spermatogonial survival and/or function
      in the rat from cyclophosphamide-induced damage, if the same principles are
      applicable in human, hormonal pretreatment should be useful for preventing the
      prolonged azoospermia caused by chemotherapy with cyclophosphamide-containing
      protocols.

PMID- 8537252
TI  - Endocrine and exocrine effects of testicular torsion in the prepubertal and adult
      rat.
AB  - Previous studies of experimental torsion have suggested that there may be
      important differences between the adult testis and the prepubertal testis in
      their responses to torsion, especially with regard to the potential for
      contralateral damage following unilateral testicular torsion. In the present
      study, adult Sprague-Dawley rats and prepubertal Sprague-Dawley rats (35 days of
      age) were subjected to unilateral 1-, 2-, and 4-hour periods of 720 degrees or
      360 degrees testicular torsion. Ipsilateral and contralateral testes were
      examined 30 and 60 days after torsion repair for effects on testis weight,
      histology, and daily sperm production (DSP). Other animals were subjected to 1
      /or 4-hour 720 degrees torsion, and testicular vein testosterone concentrations
      were determined 30 days later. In adult animals, 1-, 2-, and 4-hour 720 degrees
      torsion resulted in a significant decline in ipsilateral testis weight within 30
      days. Endocrine and exocrine function were also clearly disrupted. In prepubertal
      animals, 1-hour 720 degrees torsion significantly reduced testis weight 60 days
      after surgery. Also, prepubertal DSP values and testicular vein testosterone
      concentrations were not significantly reduced from control values by 1-hour 720
      degrees torsion when examined 30 days after surgery. Longer periods of 720
      degrees torsion resulted in damage similar to that seen in the adult animals.
      Neither adult nor prepubertal animals regained any lost function when examined 60
      days after insult. Torsion of 360 degrees induced no testicular injury in adult
      or prepubertal animals. Contralateral testes were not affected by degree or
      duration of torsion in either adult or prepubertal animals. These results suggest
      that the prepubertal testis may be more refractory to the effects of short
      periods of torsion than the adult. More importantly, these results demonstrate
      that ipsilateral torsion does not result in contralateral testicular damage in
      either adult or prepubertal animals.

PMID- 8537253
TI  - Intratesticular testosterone concentration following intratunical administration
      in the hypogonadal animal.
AB  - The serum and intratesticular testosterone concentration (ITC) after testosterone
      administration in the tunica vaginalis (TV) sac compared to parenteral
      administration was studied in 20 dogs that were rendered hypogonadal by
      gonadotropin-releasing hormone antagonist ('Nal-Glu' GnRH antagonist) in a daily
      dose of 80 micrograms for 15 days. The 20 dogs were divided into two equal
      groups. Twenty milligrams of testosterone propionate were administered in the TV
      cavity in the TV group and intramuscularly (IM) in the IM group. In addition four
      dogs acted as controls and another four as sham controls. Serum and ITC were
      determined in all the dogs 1, 2, and 15 days after testosterone administration.
      Biopsies from TV were taken 3 weeks after testosterone injection for histologic
      examination. Serum and ITC were significantly reduced (P < 0.01) 15 days after
      GnRH antagonist. They increased after intratunical testosterone administration to
      reach the pre-GnRH antagonist level (P > 0.05). After IM testosterone injection,
      the serum testosterone increased to the pre-GnRH antagonist level (P > 0.05),
      while the ITC did not. The TV did not show histopathologic abnormalities apart
      from submesothelial infiltration with inflammatory cells in one dog. In
      conclusion, TV testosterone administration delivers a major dose of testosterone
      to the testicle without exposing other tissues to high testosterone levels. The
      method is safe and may be used as an office treatment. It may be tried in the
      treatment of patients who are infertile due to a low ITC.

PMID- 8537254
TI  - Notulae seminologicae. 5. Mathematical evaluation of interdependent
      submicroscopic sperm alterations.
AB  - This paper concerns the mathematical evaluation of sperm quality as examined by
      electron microscopy. Proceeding with a Bayesian technique, we have developed a
      formula considering all statistical possibilities for defects of the examined
      sperm to be present in a sperm cell, the total number of affected spermatozoa,
      and, as consequence, that of sperm devoid of defects, also considering the
      probability of association characteristics of some of them. The formula has been
      studied in three applications. The first concerns the number of healthy
      spermatozoa present in ejaculates of fertile men. We have found an enormous
      variability, but we have observed that the minimal number of spermatozoa free of
      defects assuring a normal fertility seems to be a little higher than 2 x 10(6).
      The second and third examples concern varicocele and assisted fertilization. In
      both cases the formula allows a precise simultaneous evaluation of the totality
      of studied characters and a determination of the number of spermatozoa free from
      defects. This comparative analysis shows that the formula is sufficiently
      sensitive to distinguish the different degrees of the varicocele condition and
      the various possibilities of fertility power in cases of natural or artificial
      insemination. In this way we will easily control the level of improvement of
      sperm quality in cases of varicocele treated pharmacologically or surgically, or
      we will better predict the success of artificial insemination.

PMID- 8537255
TI  - The use of a seminal vesicle specific protein (MHS-5 antigen) for diagnosis of
      agenesis of vas deferens and seminal vesicles in azoospermic men (Vol. 15, No. 6)

PMID- 8537256
TI  - Antibiotic prophylaxis and infection control measures in minimally invasive
      surgery.

PMID- 8537257
TI  - Lack of bactericidal effect of antibiotics except aminoglycosides on Bartonella
      (Rochalimaea) henselae.
AB  - Bartonella (Rochalimaea) henselae is a cause of peliosis hepatis and bacillary
      angiomatosis, and one of the putative agents of cat scratch disease. Specific
      therapy for B. henselae infections is not available. Treatment failures and
      relapses are frequent, especially following brief antibiotic courses, and this
      contrasts with the in-vitro susceptibility of B. henselae to most antibiotics. We
      decided to test the antibiotic susceptibility of B. henselae associated with
      murine macrophage-like cells (P388 D1) and a human endothelial cell line. We
      carried out a bactericidal assay in this model and in axenic broth. In both
      models, only aminoglycosides were bactericidal. These results suggest that
      aminoglycosides may be effective in the treatment of B. henselae infections.

PMID- 8537258
TI  - Ketoconazole and itraconazole susceptibility of Candida albicans isolated from
      patients infected with HIV.
AB  - Two hundred and fifty-five isolates of Candida albicans were collected from 93
      patients infected with HIV during the course of a clinical trial comparing
      ketoconazole with itraconazole for the treatment of oropharyngeal or oesophageal
      candidosis. The susceptibility of the isolates to both drugs was determined by
      incubating 0.5-2.0 x 10(4) CFU/mL yeast in 0.25-16 mg/L drug in RPMI1640 buffered
      with MOPS for 24 h at 35 degrees C in 5%CO2 in microtitre trays. Each plate was
      agitated before reading the optical density. The IC90, IC80 and IC50 were defined
      as the lowest drug concentration to reduce the optical density to > or = 90%, 80%
      and 50% of the growth control respectively. IC90S > 0.25 mg/L of ketoconazole
      and/or itraconazole were found for 42 isolates recovered from 21 patients, 12 of
      whom had responded to treatment. IC80S > 0.25 mg/L were found for only six of
      these isolates which had been recovered from three patients, two of whom
      responded well to treatment. These results indicate that neither the IC90 nor the
      IC80 are useful in predicting clinical resistance. None of the isolates exhibited
      IC50 > 0.25 mg/L to either drug which is consistent with the low incidence of
      resistance reported for these antifungal agents.

PMID- 8537259
TI  - Structure and toxicity of amphotericin B/triglyceride emulsion formulations.
AB  - This paper investigates the relationship between the in-vitro toxicity of
      amphotericin B/triglyceride emulsion formulations, and their phospholipid
      composition and method of manufacture. Emulsion toxicity, as measured by the
      erythrocyte potassium leakage assay, was found to be dependent on the transition
      temperature of the phospholipid emulsifier, and the thermal history of the
      emulsion. Emulsions made using unsaturated phospholipids showed a low toxicity
      irrespective of the method of manufacture. Emulsions made using phospholipids
      with phase transition temperatures above the maximum process temperature
      displayed a toxicity comparable to the deoxycholate-solubilized formulation. This
      toxicity was significantly reduced when such formulations were heated to a
      temperature above the phase transition temperature for the phospholipid. We
      interpret these data as demonstrating that the amphotericin molecule must be
      inserted fully into the phospholipid emulsifier in order to produce a low
      toxicity emulsion, and that this insertion is critically dependent on the
      composition of the emulsifier and its phase transition properties.

PMID- 8537260
TI  - Acquired resistance in Mycobacterium avium complex strains isolated from AIDS
      patients and beige mice during treatment with clarithromycin.
AB  - Clarithromycin has been reported to select clarithromycin resistant mutants of
      Mycobacterium avium complex (MAC) during treatment with clarithromycin in AIDS
      patients and beige mice. We selected resistant mutants in vitro at a frequency of
      5 x 10(-9). Clarithromycin resistant strains of MAC isolated in AIDS patients and
      beige mice as well as derivatives selected in vitro had a unique pattern of
      acquired cross-resistance to macrolides and related antibiotics. In contrast, the
      pattern of resistance to non-macrolide antibiotics remained unchanged in
      clarithromycin resistant strains. A dramatic decrease in ribosome affinity for
      clarithromycin and erythromycin was found in clarithromycin resistant strains,
      but no mutation was found in the peptidyl domain of the 23S rRNA, indicating that
      another ribosomal modification is involved.

PMID- 8537261
TI  - The scid mouse as an experimental model for the evaluation of anti-Pneumocystis
      carinii therapy.
AB  - The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as
      a model for experimental chemotherapy was examined using standard compounds known
      to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to
      reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose
      range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30
      treatments). However, alterations in associated symptoms of infection (reduced
      body weight, increased lung weight, increased blood leucocytes and erythrocytes),
      was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of
      sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole
      was dose-dependent, but not linear with dose, and was apparently correlated to
      cyst reduction; trimethoprim was below the limit of detection at this time.
      Treatment of mice with 100/500 mg/kg/day trimethoprim/sulphamethoxazole required
      2 weeks (bd for 10 days of treatment) before changes in indices of infection
      became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks)
      was nearly as effective as high-dose trimethoprim/sulphamethoxazole in reducing
      cysts, whereas lower doses were ineffective. Despite being unable to reduce
      pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc,
      three times per week for 3 weeks) were able to reduce lung weights and blood
      leucocyte levels. This model of pulmonary P. carinii infections is amenable to
      chemotherapeutic intervention in an apparently dose-dependent fashion, and can be
      used to evaluate the capacity of compounds to eradicate P. carinii and resolve
      signs of infection.

PMID- 8537262
TI  - Roxithromycin disposition in patients on continuous ambulatory peritoneal
      dialysis.
AB  - Roxithromycin is a macrolide antibiotic with a spectrum of activity similar to
      erythromycin. Roxithromycin has been shown to have a favourable pharmacokinetic
      profile with more reliable absorption and higher, prolonged plasma and tissue
      concentrations compared with erythromycin. The pharmacokinetics and dialysis
      clearance of roxithromycin were studied in twelve patients with end-stage renal
      disease on continuous ambulatory perionteal dialysis. Following a single 300 mg
      oral dose, multiple blood, dialysate and urine samples were collected over 48 h
      and assayed for roxithromycin by a microbiological method. Peak plasma
      concentrations were attained between 0.5 and 5 h, and ranged from 2.3 to 6.8
      mg/L. The mean elimination half-life was 20.6 +/- 8.7 h, compared with 10 to 14 h
      previously reported in healthy volunteers given a single 300 mg dose. Plasma
      clearance relative to bioavailability (Clp/F) ranged from 37.3 to 118.3 mL/min.
      The percentage of the dose recovered in the dialysate and net dialysis clearance
      were low, ranging from 1.0 to 3.1% and 0.9 to 1.8 mL/min, respectively. Only 1%
      of the dose was recovered in the urine. These results demonstrate that
      roxithromycin is not substantially removed by continuous ambulatory peritoneal
      dialysis, and its elimination is prolonged in renal failure, possibly due to
      impaired nonrenal elimination.

PMID- 8537263
TI  - The pharmacokinetics of meropenem in surgical patients with moderate or severe
      infections.
AB  - The pharmacokinetics of meropenem were studied in a group of 11 surgical patients
      (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had
      moderate or severe infection and who received a mean dose of 14.5 mg/kg +/- 2.7
      meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were
      collected at timed intervals after the first dose on day 1 and the second dose on
      the fourth or fifth day of therapy. Serum meropenem concentrations were assayed
      by HPLC and fitted to a two compartment pharmacokinetic model. The mean
      pharmacokinetic parameters (+/- standard deviation) on day 1 were T1/2 84.6 +/-
      24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67
      mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the
      values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417
      mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2,
      Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not
      statistically significant (Student's t-test, P > 0.05). Total clearance of
      meropenem was linearly related to creatinine clearance or patient age on the
      first day of therapy. Although the T1/2 and MRT were longer and the Cltot lower
      than those reported for young healthy volunteers, they were similar to those
      found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537264
TI  - A comparison of 5 days of dirithromycin and 7 days of clarithromycin in acute
      bacterial exacerbation of chronic bronchitis.
AB  - The safety and efficacy of dirithromycin and clarithromycin were compared in a
      single-blind, multicentre study of patients with acute bacterial exacerbation of
      chronic bronchitis (AECB). Patients received either dirithromycin, 500 mg once
      daily for 5 days, or clarithromycin, 250 mg twice daily for 7 days. A total of
      212 patients entered the study, of whom 191 qualified for efficacy analysis.
      Favourable post-therapy clinical and bacteriological response rates for qualified
      patients (95 dirithromycin and 96 clarithromycin) were similar: 89.5% and 68.8%
      for dirithromycin vs 94.8% and 71.9% for clarithromycin. At late post-therapy
      evaluation, favourable clinical and bacteriological response rates were achieved
      in 98.8% and 96.2% of dirithromycin patients and 95.3% and 93.3% of
      clarithromycin patients, respectively. These differences were neither
      statistically nor clinically significantly different. Both drugs had similar
      efficacy against Haemophilus influenzae and both were well tolerated.
      Dirithromycin, administered as a single daily dose for just 5 days resulted in
      complete compliance in all but four patients. In clarithromycin-treated patients,
      requiring a 7-day course of twice-daily treatment, compliance was less
      satisfactory, with 12 patients failing to comply, though the between-group
      difference was not statistically significant. It can be concluded that 5 days of
      dirithromycin, 500 mg once daily is as safe and effective as 7 days of
      clarithromycin, 250 mg, twice daily in the treatment of AECB.

PMID- 8537265
TI  - Equivalent efficacies of meropenem and ceftazidime as empirical monotherapy of
      febrile neutropenic patients. The Meropenem Study Group of Leuven, London and
      Nijmegen.
AB  - The efficacies of meropenem, a novel carbapenem, and ceftazidime, as empirical
      therapy of febrile neutropenic patients, were compared in a prospective,
      randomized clinical trial. One hundred and twelve adult patients were given
      meropenem 1 g tds iv for 153 episodes of fever, while 109 patients received
      ceftazidime 2 g tds iv for 151 episodes. All patients survived the first 3 days
      of therapy and, by the end of the treatment courses, 67 (44%) episodes had
      responded to meropenem, compared with 62 (41%) to ceftazidime. Eighty (53%)
      episodes initially treated with ceftazidime and 63 (41%) episodes treated with
      meropenem were considered to have failed treatment because it was thought
      necessary to administer additional antibacterial agents; however, modifications
      were made twice as often because of fever that persisted beyond 2-3 days than
      because of obvious causes of failure such as persistent infection. Three patients
      in the ceftazidime group and five in the meropenem group died. Meropenem was well
      tolerated, with no reports of nausea or toxicity to the central nervous system.
      Although ceftazidime was shown in the present study to be as effective as
      meropenem, the broader spectrum of activity of meropenem against Gram-positive
      cocci suggests that it might be more appropriate as empirical therapy of febrile
      neutropenic patients who are at high risk of acquiring infections caused by these
      bacteria.

PMID- 8537266
TI  - An audit of ciprofloxacin use in a district general hospital.
AB  - An audit of ciprofloxacin use at Southmead Hospital, Bristol was carried out for
      forty patients treated in early 1992 employing a modified Delphi technique with
      six assessors. Most patients assessed (20/40, 50%) had urinary tract infections
      (UTIs), 5/40 (12.5%) had chest infections, 4/40 (10%) had bacterial
      gastroenteritis and 3/40 (7.5%) had either bacteraemia or infection following an
      orthopaedic procedure. A likely bacterial pathogen was isolated from 32/40 (80%)
      of patients; 14/32 (44%) had Pseudomonas aeruginosa infections and from the
      remainder Enterobacteriaceae including Salmonella spp. (non-typhoid) were
      cultured. Oral therapy with ciprofloxacin was used in 37 (93%) of the 40
      patients, and the three others received iv treatment. In 21/35 (60%) of patients
      where an assessment was made by majority scoring, a quinolone was felt to be
      clinically justified. A quinolone was least likely to be thought justified if the
      patient had a chest infection. The assessors had few concerns about the
      effectiveness or toxicity of ciprofloxacin but for 41% (14/34) of patients, where
      there was a majority opinion, a cheaper alternative was felt to be available;
      most of these patients had hospital-acquired UTIs caused by Enterobacteriaceae.
      The duration of therapy was felt to be too long in 35% (10/29) of patients,
      mainly because of prolonged treatment of UTIs. In some cases of P. aeruginosa
      infection the assessors would have used higher doses than those prescribed.
      Ciprofloxacin was the quinolone of choice in 24/32 (75%) of assessable cases.
      Norfloxacin was chosen to treat UTI due to multi-resistant Enterobacteriaceae in
      6.2% (2/32) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537267
TI  - SYN987, SYN1193, and SYN1253, new quinolones highly active against gram-positive
      cocci.
AB  - SYN987, 1193 and 1253 are new fluorinated quinolones with enhanced activity
      against Gram-positive bacteria. The MICs of SYN 987, 1193 or 1253 were studied by
      an agar dilution method against 88 streptococci (including penicillin resistant
      Streptococcus pneumoniae), 30 enterococci and 62 Staphylococcus aureus. SYN 987,
      1193 and 1253 were 2 to 4 times more active than sparfloxacin and 16-64 times
      more active than older fluoroquinolones against all streptococci and
      ciprofloxacin-resistant S. aureus. This study demonstrates that SYN 987, 1193 and
      1253 are extremely potent antibacterial agents which deserve further evaluation.

PMID- 8537268
TI  - In-vitro activity of a new quinolone (CP-99,219) compared with ciprofloxacin,
      pefloxacin, azithromycin and penicillin against Neisseria gonorrhoeae.
AB  - The in-vitro activities of CP-99, 219, ciprofloxacin, pefloxacin, azithromycin
      and penicillin was tested against 114 Neisseria gonorrhoeae strains. The MIC90s
      were: 0.008 mg/L (MIC range 0.001-0.06 mg/L) for CP-99, 219, 0.008 mg/L (MIC
      range 0.001-0.25 mg/L) for ciprofloxacin, 0.12 mg/L (MIC range 0.008-4 mg/L) for
      pefloxacin, 0.25 mg/L (MIC range 0.03-1 mg/L) for azithromycin and 16 mg/L (MIC
      range 0.015-16 mg/L) for penicillin. The activity of CP-99,219 against various N.
      gonorrhoeae isolates was comparable to ciprofloxacin.

PMID- 8537269
TI  - Comparative susceptibility of Legionella pneumophila and Legionella longbeachae
      to 12 antimicrobial agents.
AB  - The in-vitro susceptibilities of 28 strains each of Legionella pneumophila and
      Legionella longbeachae to 12 antibiotics were compared by an agar dilution
      technique. A limited comparison with disc testing was also performed. Most
      antibiotics were less active against L. longbeachae, although MICs of
      erythromycin, ciprofloxacin and rifampicin suggest potential clinical utility.

PMID- 8537270
TI  - Susceptibility of enterococci, methicillin-resistant Staphylococcus aureus and
      Streptococcus pneumoniae to the glycylcyclines.
AB  - The in-vitro activities of two glycylcyclines, DMG-MINO and DMG-DMDOT, and
      several comparative agents were determined against 263 enterococci, 102
      methicillin-resistant Staphylococcus aureus and 55 Streptococcus pneumoniae
      recent clinical isolates. The glycylcyclines and teicoplanin were the most active
      agents against the enterococcal isolates. All methicillin-resistant S. aureus
      were susceptible to the glycylcyclines. Only DMG-DMDOT, ciprofloxacin,
      teicoplanin and vancomycin exhibited comparable activity against penicillin
      susceptible, -intermediate and -resistant S. pneumoniae strains.

PMID- 8537271
TI  - Fluoroquinolones and bacterial enteritis, when and for whom?
AB  - During the last decade quinolones such as norfloxacin, ciprofloxacin, ofloxacin
      and fleroxacin have emerged as drugs of choice for treatment of various bacterial
      enteric infections. Controlled studies have shown that quinolones, administered
      in varying regimens ranging from a single dose to 5 days treatment, significantly
      reduce the intensity and severity of travellers' diarrhoea as well as
      shigellosis. They have also been found to be highly effective in the treatment of
      invasive non-typhoid salmonellosis as well as typhoid fever. Results from trials
      evaluating quinolone treatment of uncomplicated salmonella and campylobacter
      enteritis have generally been disappointing. We studied norfloxacin for the
      empirical treatment of suspected bacterial enteritis of less than 6 days duration
      in a large placebo controlled trial. Although statistical differences in clinical
      outcome favouring norfloxacin were found among 259 culture positive patients, the
      differences were not striking and of doubtful clinical importance. However, a
      clear beneficial effect of norfloxacin, resembling that observed in early
      treatment of travellers' diarrhoae was found among the severely ill patients who
      initiated treatment within 48 h of onset of symptoms to start of treatment seemed
      to be of major importance in relation to therapeutic efficacy. Quinolone
      treatment of bacterial enteritis is furthermore limited by the rapid development
      of resistance seen in Campylobacter spp. and the failure of these compounds to
      eradicate Salmonella spp. Presently quinolones can be recommended in treatment of
      travellers' diarrhoea and shigellosis as well as enteric fever. They have limited
      usefulness for the routine empirical treatment of bacterial enteritis caused by
      Salmonella spp and Campylobacter spp. Treatment should be restricted to early
      empirical treatment of the severely ill and vulnerable patients with an
      underlying health problem.

PMID- 8537272
TI  - Effect on Pseudomonas aeruginosa alginate expression of direct plating and
      culture of fresh cystic fibrosis sputum on to pseudomonas isolation agar
      containing subinhibitory concentrations of roxithromycin and rifampicin.
AB  - The effects of subinhibitory concentrations of roxithromycin (16 mg/L) or
      rifampicin (16 mg/L) on alginate production by Pseudomanas aeruginosa were
      investigated. The weight of purified alginate from antibiotic-free cultures was
      significantly greater (52.5 +/- 24.0 mg, range 22.4-109.5), compared with
      alginate from cultures bacteria exposed to sub-MIC of roxithromycin (21.9 +/-
      17.0, 0.0-42.1 (P < or = 0.037)) and to sub-MIC of rifampicin (28.6 +/- 15.0, 2.9
      47.5 (P < or = 0.038)). Chromatographic analysis of hydrolysed and chemically
      transformed sub-units of alginate revealed that the presence and the molar ratio
      of D-mannuronic acid and L-guluronic acid were not affected in the remnant
      alginate exposed to sub-MIC of roxithromycin in contrast to that in the remnant
      alginate exposed to sub-MIC of rifampicin.

PMID- 8537273
TI  - Detection of high- and moderately high-level resistance to gentamicin and
      streptomycin in Enterococcus faecium by a disc diffusion method.
AB  - We evaluated an agar disc diffusion test for the detection of high-level (> or =
      2000 mg/L) and moderately high-level resistance to gentamicin (MIC, > or = 128- <
      or = 1024 mg/L) and streptomycin (MIC, > or = 256- < or = 1024 micrograms/ml)
      with 70 clinical isolates of Enterococcus faecium. Results obtained using disks
      containing 120 micrograms gentamicin and 300 micrograms streptomycin were
      compared with MICs determined by an agar dilution method. Based on the
      scattergrams, the closest zone diameter correlations with MIC breakpoints were as
      follows: susceptible, > or = 16 mm; and resistant, < or = 10 mm, for both
      streptomycin and gentamicin. No major or very major errors were found with either
      aminoglycoside using these values. We conclude that agar disk diffusion test can
      be used to accurately detect high-level or moderately high-level gentamicin and
      streptomycin resistance in E. faecium.

PMID- 8537275
TI  - An investigation of the pharmacokinetics and autoinduction of rifabutin
      metabolism in mice treated with 10 mg/kg/day six times a week for 8 weeks.
AB  - Plasma, lung and spleen concentrations of rifabutin have been measured in mice
      after single and multiple oral administrations of the drug. Rifabutin
      concentrations in spleen were similar to those measured in plasma, whereas
      concentrations in lung were higher. No significant autoinduction of rifabutin
      metabolism was observed.

PMID- 8537274
TI  - Bactericidal effect of beta-lactams and amikacin alone or in association against
      Klebsiella pneumoniae producing extended spectrum beta-lactamase.
AB  - Ten extended spectrum beta-lactamases producing strains of Klebsiella pneumoniae
      characterized by analytical isoelectric focusing and studied for their
      susceptibility to beta-lactam antibiotics, either alone or in combination with a
      beta-lactamase inhibitor (clavulanic acid and sulbactam) and in association with
      amikacin. The extended spectrum beta-lactamases were derived from either TEM (CTX
      1 = TEM-3) or SHV (CAZ-4 = SHV-5). Killing curves were studied with antibiotics
      at clinical by achievable concentrations, at MIC and MIC x 4. At MIC, cefotetan,
      cefotaxime and ceftazidime lacked bactericidal activity. Imipenem was more
      rapidly bactericidal than meropenem or co-amoxiclav. At MIC x 4, cefotetan and
      cefotaxime exhibited bactericidal effect but this was less than for imipenem
      which gave a reduction of 4 log10 of the inoculum. Cefotaxime plus sulbactam gave
      no bactericidal effect compared with cefotaxime plus co-amoxiclav. A bactericidal
      effect with cefotaxime plus sulbactam was seen with the addition of amikacin. At
      clinical concentrations cefotaxime plus co-amoxiclav +/- amikacin was as
      efficient as imipenem +/- amikacin with a rapid bactericidal effect (5-6 log10 in
      30-60 min). We proposed that cefotaxime+co-amoxiclav might be considered as an
      alternative to imipenem for the treatment of extended spectrum beta-lactamase
      associated K. pneumoniae injections.

PMID- 8537276
TI  - Ampicillin plus ciprofloxacin therapy of experimental endocarditis caused by
      multidrug-resistant Enterococcus faecium.
AB  - The combination of ampicillin and ciprofloxacin displayed bactericidal in-vitro
      activity against two strains of Enterococcus faecium which were highly resistant
      to ampicillin, vancomycin, and aminoglycosides. This antibiotic combination was
      used to treat rabbits with experimental endocarditis caused by these strains.
      Although a significant decrease in vegetation bacterial counts occurred with one
      strain, the degree of killing did not approach that of penicillin with an
      aminoglycoside against susceptible enterococci.

PMID- 8537277
TI  - A placebo controlled evaluation of lomefloxacin in the treatment of bacterial
      diarrhoea in the community.
AB  - We compared 40 patients taking lomefloxacin 400 mg once daily for 5 days in a
      double blind trial with 44 placebo takers with proven community acquired
      bacterial diarrhoea (85% due to Campylobacter spp.). Lomefloxacin eradicated
      Campylobacter spp. in 75% but did not alter clinical outcome. Twenty-eight per
      cent of the campylobacter isolates developed resistance. Thirty-three per cent
      developed side-effects. Lomefloxacin is not recommended for community-acquired
      bacterial diarrhoea when Campylobacter spp. predominate.

PMID- 8537278
TI  - Klebsiella oxytoca revealing decreased susceptibility to extended spectrum beta
      lactams.

PMID- 8537279
TI  - Analysis of beta-lactamases produced by cephalothin-susceptible Escherichia coli
      clinical isolates resistant to co-amoxiclav and ticarcillin-clavulanic acid. The
      CERIB Study Group.

PMID- 8537280
TI  - Quinolone resistance in clinical strains of Campylobacter jejuni and
      Campylobacter coli.

PMID- 8537281
TI  - A pharmacokinetic and safety evaluation of a 28 day course of oral acyclovir in
      elderly patients with herpes zoster.

PMID- 8537282
TI  - Lower respiratory tract infection due to ciprofloxacin resistant Moraxella
      catarrhalis.

PMID- 8537283
TI  - Sequence analysis of two chromosomally mediated inducible beta-lactamases from
      Aeromonas sobria, strain 163a, one a class D penicillinase, the other an AmpC
      cephalosporinase.
AB  - Two beta-lactamase genes from Aeromonas sobria, strain 163a, have been cloned and
      sequenced, one encoding a typical class C cephalosporinase, designated CepS, the
      other a class D penicillinase, designated AmpS. CepS is predicted to be a mature
      protein of 38 kDa with a pI value of 7.0. The amino acid sequence of CepS is most
      similar to that of AmpC from Pseudomonas aeruginosa (54.7%). AmpS is predicted to
      be a mature protein of 27 kDa with a pI value of 7.9 that mostly closely
      resembles BLAD from Klebsiella pneumoniae (42.2%), and OXA-1 from Escherichia
      coli (36.6%), beta-lactamases that are encoded by genes carried on multiresistant
      transposons. AmpS differs significantly from the other class D beta-lactamases in
      that it hydrolyses cloxacillin poorly and is inducible. Both genes exhibit a high
      overall GC content and possess a high NNC and NNG codon preference, similar to
      that of genes from Pseudomonas spp.

PMID- 8537284
TI  - Potent activity of meropenem against Escherichia coli arising from its
      simultaneous binding to penicillin-binding proteins 2 and 3.
AB  - A mutant strain of Escherichia coli with reduced susceptibility to imipenem,
      designated TL2740, was selected following serial passage of the parent strain, E.
      coli C600, in broth containing increasing concentrations of the carbapenem; the
      MIC of imipenem for TL2740 was eight-fold greater than that of the parent strain.
      The mutant also exhibited reduced susceptibilities to panipenem and biapenem and
      high-level resistance to mecillinam, but was as susceptible to meropenem,
      ceftazidime, piperacillin and the other beta-lactams tested as strain C600. The
      affinity of penicillin-binding protein (PBP) 2 of TL2740 for imipenem and
      meropenem was ten-fold less than that of C600, thereby providing an explanation
      for the mutant's reduced susceptibility to some carbapenems and mecillinam.
      However, this theory was confounded by the observation that the in-vitro
      activities of meropenem against both parent and mutant strains were virtually the
      same and by the fact that PBP 2 is the principal target of the antibiotic.
      Imipenem and aztreonam, which bind to PBP 2 and PBP 3 respectively, demonstrated
      synergic activity when tested in combination against both C600 and TL2740. These
      results suggest that the potent activity of meropenem against the mutant strain
      might also be due to a synergic effect resulting from simultaneous binding to
      both PBP 2 and PBP 3 and that the variable activities of the carbapenems against
      TL2740 were related to their different PBP binding profiles. Compared with C600,
      TL2740 appeared shorter on electron microscopy and had a longer generation time,
      discrepancies which are compatible with defective PBP 2 activities in the mutant
      strain. We also identified three clinical isolates of E. coli with beta-lactam
      susceptibility profiles which resembled that of TL2740 i.e. high-level resistance
      to mecillinam and low-level resistance to carbapenems, with the exception of
      meropenem to which these strains were susceptible; in common with TL2740, the
      combination of imipenem and aztreonam was synergic against these isolates. The
      genetic basis of resistance in all of the mecillinam-resistant strains, including
      TL2740, mapped close to lip at 15' on the E. coli chromosome with transductional
      analysis. The results strongly suggest that the reduced susceptibilities of the
      clinical isolates to carbapenems were due to mutations in the genes encoding the
      PBP 2s of these strains which affected their affinities for beta-lactam
      antibiotics.

PMID- 8537285
TI  - Molecular epidemiology of ceftazidime resistant Enterobacteriaceae from patients
      on a paediatric oncology ward.
AB  - Between the autumn of 1989 and January 1990, 21 of the 44 children on the
      paediatric oncology ward of St. James's University Hospital, Leeds, UK were
      infected or colonised with Enterobacteriaceae producing extended-spectrum beta
      lactamases. This represents 48% of the patients on the ward. Only six patients
      (14%) had microbiologically proven septicaemia caused by such bacteria during
      this period. Eighty-one isolates of Enterobacteriaceae producing extended
      spectrum beta-lactamases derived from blood culture (7 isolates from 6 patients)
      or faecal samples (74 isolates) were available for examination. These comprised
      28 Escherichia coli, 28 Klebsiella oxytoca, 11 Klebsiella pneumoniae, 10
      Citrobacter freundii, 3 Enterobacter spp. and 1 Serratia marcescens. Clinical
      isolates were resistant to penicillins and to ceftazidime. Strains isolated in
      this study also showed multiple resistance to a range of antimicrobial agents.
      Transfer to a nalidixic acid resistant laboratory strain of E. coli UB5201 was
      attempted, but transfer of the ceftazidime resistance determinant was only
      successful in 25 isolates (31%). Examination of plasmid DNA revealed sequences in
      each isolate that hybridised with the TEM beta-lactamase gene probe used on a
      variety of plasmids ranging in size from 2.5- > 150 kb, sometimes found on
      several replicons in a single isolate. The TEM gene probe also hybridised with
      chromosomal DNA in a large number of isolates. Nucleotide sequence analysis
      demonstrated the presence of three extended-spectrum beta-lactamases: TEM-10B
      produced by two isolates, TEM-12B produced by 37 isolates and TEM-26B produced by
      40 isolates. In two cases, isolates produced two beta-lactamases, and it proved
      impossible to identify these enzymes unequivocally. The genes encoding TEM-10B
      and TEM-26B both differ from TEM-12B by single nucleotide substitutions. Analysis
      of the ribotype patterns derived from the clinical isolates provided evidence for
      cross-colonisation between patients, and this was confirmed by analysis of the
      plasmid profiles. Four years after discontinuing ceftazidime and other extended
      spectrum cephalosporins on this ward, patients were still colonised with bacteria
      that produced extended-spectrum beta-lactamases.

PMID- 8537286
TI  - Speculations on the influence of infecting phenotype on virulence and antibiotic
      susceptibility of Legionella pneumophila.
AB  - It is not clear how Legionella pneumophila, which is a ubiquitous aquatic
      organism not possessing a mammalian reservoir, evolved the ability to cause human
      disease. The unusual ecology of the organism may play an important role in the
      transmission and virulence of legionella infections. L. pneumophila can infect
      and kill specific species of free-living amoebae as well as multiplying as an
      intracellular parasite in human phagocytic cells. In nature L. pneumophila can
      survive and possibly replicate in free suspension, and grow in biofilms and in
      protozoa thus leading to diverse phenotypes, potentially with diverse virulence
      and susceptibility properties. Indeed, recent evidence shows that intra-amoeba
      growth induces a phenotype that is dramatically different physiologically to that
      obtained in vitro, with altered virulence and susceptibility properties. Growth
      in macrophages also has profound effect on the physiological properties of L.
      pneumophila. Many different stress proteins are expressed by the organism as a
      result of intra-macrophage growth. A heat shock protein is abundantly synthesised
      and may be presented on the surface of infected macrophages, which allows them to
      be targeted by T-lymphocytes for destruction. The difficulties in successfully
      treating Legionnaires' disease are probably influenced by the intracellular
      location of L. pneumophila. Retrospective clinical studies show that it is only
      drugs such as erythromycin, ciprofloxacin and rifampicin, which are capable of
      accumulating in phagocytic cells, that are efficacious in the treatment of
      legionnaires' disease. Despite the use of such drugs treatment failures occur,
      but these do not appear to be associated with the emergence of resistant strains.
      Studies have shown that although erythromycin and rifampicin can inhibit the
      multiplication of L. pneumophila in macrophages the organism is not killed and
      can resume multiplying when the drugs are removed. Thus a competent cell mediated
      immune response is important in recovery from legionella infections. There is an
      urgent need for greater understanding of how the changes induced by intracellular
      growth affect sensitivity to antibiotics and of how the changes induced by
      intracellular growth affect sensitivity to antibiotics and host defences.
      Immunocompromised patients, who have the highest mortality rates, are likely to
      gain the most from progress in the treatment of L. pneumophila infections.

PMID- 8537287
TI  - Evaluation of the Epsilometer test (E test) for testing the susceptibility of
      coagulase-negative staphylococci to teicoplanin.
AB  - The antimicrobial susceptibilities of 118 clinical isolates of coagulase-negative
      staphylococci to teicoplanin were determined by disc diffusion and the
      Epsilometer test (E test) and the results were compared with the MICs determined
      by the agar dilution method of the National Committee for Clinical Laboratory
      Standards (NCCLS). There was a poor correlation of r = 0.5 between the zone
      diameters of inhibition and agar dilution MICs and 10 and four of the 11 isolates
      for which the MICs were > or = 32 mg/L were misclassified as susceptible by the
      disc test after applying the interpretative criteria of the NCCLS and the Comite
      de l'Antibiogramme de la Societe Francaise de Microbiologie (CASFM),
      respectively. The E test tended to result in MICs that were lower than those
      determined by agar dilution and only 66% of MIC were within +/- 1 log2 dilution
      of each other. Only one of 11 resistant strains was detected by the E test and,
      although there was no false resistance, six resistant strains were misclassified
      as susceptible after applying the criteria of the NCCLS as were four such
      isolates when the criteria of the CASFM were employed, probably as a result of
      using too light an inoculum. Disc diffusion is not a reliable means of
      determining the susceptibility of coagulase-negative staphylococci but might be
      replaced by the E-test provided that discrepant results can be resolved by using
      a denser inoculum.

PMID- 8537288
TI  - Evaluation of the E test system versus a microtitre broth method for antifungal
      susceptibility testing of yeasts against fluconazole and itraconazole.
AB  - The E test strip (AB Biodisk, Solna, Sweden) as an antimicrobial susceptibility
      testing method is a new and promising tool with broad application in
      microbiology. This method is less labour intensive than broth dilution methods
      and may be useful for testing individual clinical isolates. In contrast to
      several publications comparing E test antibacterial strips with NCCLS reference
      methods, there is little information about the performance of E test antifungal
      strips. This study compared fluconazole and itraconazole MICs obtained by E test
      with a microbroth dilution method performed to NCCLS guidelines. Fluconazole and
      itraconazole E test results exhibited good correlation with the broth
      microdilution (82% and 81% agreement within +/- 1 two-fold dilution,
      respectively). The E test is easy to perform and generates MICs for Candida
      species in 24 h.

PMID- 8537289
TI  - Managed care. Are we ready for the changes?

PMID- 8537290
TI  - Overview of newborn screening in Arkansas.

PMID- 8537291
TI  - An update on cardiogenic shock.

PMID- 8537292
TI  - Increased hepatitis incidence in Arkansas and surrounding states.

PMID- 8537293
TI  - Arkansas HIV/AIDS report 1983-1995.

PMID- 8537295
TI  - 1995 Arkansas Medical Society membership roster as of November 10, 1995.

PMID- 8537294
TI  - Radiological case of the month. L3 posterior element metastasis.

PMID- 8537296
TI  - Myosin light chain kinase from vascular smooth muscle inhibits the ATP-dependent
      interaction between actin and myosin by binding to actin.
AB  - Myosin light chain kinase (MLCK) was prepared from smooth muscle of bovine aorta.
      MLCK inhibited the ATP-dependent movement of actin filaments on a glass surface
      coated with smooth muscle myosin that had been phosphorylated. The inhibitory
      effect was abolished by calmodulin in the presence of Ca2+ (Ca-CaM). The
      abolition was also observed when the concentration of actin filaments was
      increased. The inhibitory effect and its abolition were related to the actin
      binding activity of MLCK, that is antagonized by Ca-CaM.

PMID- 8537297
TI  - Thermostable ornithine aminotransferase from Bacillus sp. YM-2: purification and
      characterization.
AB  - Thermostable L-ornithine: alpha-ketoglutarate delta-aminotransferase (L
      ornithine: 2-oxo-acid 5-aminotransferase) [EC 2.6.1.13] was purified to
      homogeneity from Bacillus sp. YM-2. The enzyme has a molecular weight of about
      82,000 and consists of two subunits with identical molecular weights. The enzyme
      catalyzes transamination from L-ornithine to alpha-ketoglutarate, producing L
      glutamate and L-glutamate gamma-semialdehyde, which is spontaneously dehydrated
      to L-delta 1-pyrroline-5-carboxylate, and the enzyme is most active at 70 degrees
      C. In addition to L-ornithine, the enzyme unexpectedly acts on D-ornithine, the
      reaction rate being 6% of that for L-ornithine. The enzyme contains 1 mol each of
      pyridoxal 5'-phosphate and another vitamin B6 compound per mol. The enzyme
      released the bound pyridoxal 5'-phosphate, as judged from the absorption at 425
      nm on incubation with 2.0 M guanidine hydrochloride. The resultant inactive
      enzyme still gave a 340-nm peak and contained 1 mol of the vitamin B6 compound.
      The partial amino acid sequence shows high homology with those of mammalian and
      yeast ornithine delta-aminotransferases.

PMID- 8537298
TI  - Transcriptional regulation of catalase gene in the fission yeast
      Schizosaccharomyces pombe: molecular cloning of the catalase gene and northern
      blot analyses of the transcript.
AB  - Exposure of Schizosaccharomyces pombe cells to various stresses including 0.2 mM
      hydrogen peroxide, 50 microM menadione, 10 J/m2 of UV irradiation at 255 nm, and
      high osmolarity (0.5 M sorbitol or 0.3 M NaCl) induces catalase [EC 1.11.1.6]
      activity. A part of the catalase gene of S. pombe was amplified by PCR with
      oligonucleotide primers designed from amino acid sequences conserved in several
      species of catalases. The catalase gene including its flanking sequence of S.
      pombe was cloned from a genomic DNA library of S. pombe, which was constructed on
      the EMBL3 vector, using the PCR-amplified DNA as a radioactive probe. A 3.5 kb
      HindIII fragment, which hybridized with the PCR-amplified probe, was subcloned
      into pUC19 and sequenced. The fragment contains one long open reading frame
      without any intron. The polypeptide deduced from the nucleotide sequence consists
      of 512 amino acid residues and is homologous to several other catalases. Amino
      acid sequences of the proteolytic peptides obtained from the purified catalase of
      S. pombe coincided with the amino acid sequence predicted from the DNA sequence.
      Transcription of this gene starts at 370 bases upstream of the initiation
      methionine codon. Northern blot analyses of the catalase mRNA revealed that the
      stresses which induce the catalase activity also induce the transcription of the
      catalase gene. The induction of the catalase mRNA by hydrogen peroxide is not
      inhibited by cycloheximide or staurosporine.

PMID- 8537299
TI  - Activation of adenylate cyclase by divalent cations and polyamines in saponin
      treated Dictyostelium discoideum cells.
AB  - Binding of an intrinsic agonist (cyclic AMP) to specific receptors on the cell
      surface induces transmembrane signals for the activation of adenylate cyclase in
      the cellular slime mold Dictyostelium discoideum. We found that stimulation by
      CaCl2, MgSO4 or polyamines having two to four positive charges induced the
      activation of adenylate cyclase in cells treated with saponin. The activation was
      roughly identical to the stimulation of the intrinsic agonist both in amount and
      in time course. The intact cells (saponin-untreated cells) responded to neither
      divalent cations nor polyamines. While saponin is known to have a detergent-like
      effect and to make the plasma membrane permeable, low molecular weight dyes did
      not penetrate the plasma membrane under our conditions for the saponin-treatment.
      Caffeine is known to inhibit the cAMP-induced activation of adenylate cyclase by
      blocking signal transduction, but not by acting directly on the enzyme [Brenner,
      M. and Thoms, S.D. (1984) Dev. Biol. 101, 136-146]. We found that caffeine
      inhibited the cation-induced activation. These results suggest that these
      divalent and polyvalent cations do not act directly on adenylate cyclase but that
      they mimic or induce the transmembrane activation signal for adenylate cyclase in
      the saponin-treated cells.

PMID- 8537300
TI  - Cloning and sequence analysis of cDNA for a possible DNA-binding protein 5E5 in
      the nervous system.
AB  - Monoclonal antibody 5E5 recognized an intranuclear antigen of neurons in the rat.
      We isolated 5E5cDNA and determined its nucleotide and deduced amino acid
      sequences. The 5E5cDNA had an open reading frame of 825 amino acids and its amino
      acid sequence showed no significant homology to any protein or to any DNA binding
      motif so far known. 5E5 protein had an abundance of basic amino acids, especially
      arginine, and included a glycine-rich region and a proline cluster. Monoclonal
      antibody 12H raised against 5E5cDNA fusion protein recognized an intranuclear
      substance in rat brain sections and a single protein band of about 98 kDa in the
      brain nuclear extract fraction on immunoblotting. DNA-cellulose column
      chromatography indicated that 5E5 protein might have DNA-binding ability.
      Transfection studies indicated that 5E5 protein expressed in COS-1 is localized
      in cell nuclei. These results suggest that 5E5 protein is a possible DNA-binding
      protein which is expressed especially in neurons.

PMID- 8537301
TI  - Role of the N- and C-terminal domains of bovine beta 2-glycoprotein I in its
      interaction with cardiolipin.
AB  - beta 2-Glycoprotein I (beta 2-GPI) is a cofactor in the recognition of the
      phospholipid antigen cardiolipin by anti-cardiolipin antibodies in autoimmune
      diseases such as systemic lupus erythematosus. We examined the interactions of
      various forms of bovine beta 2-GPI, such as its intact form, desialylated form
      (Asialo-beta 2-GPI), N-terminal domain (Domain I), and modified forms of beta 2
      GPI and Asialo-beta 2-GPI with nicks in their C-terminal domains, with
      phospholipid liposomes under different conditions of pH and ionic strength. We
      found that at neutral pH and low ionic strength, beta 2-GPI became bound to
      liposome membranes containing cardiolipin, phosphatidylglycerol,
      phosphatidylserine, phosphatidylserine, phosphatidic acid, or
      phosphatidylinositol, but not phosphatidylcholine alone. The number of
      phospholipids involved in the binding seemed to depend on the head group
      structure of the negatively charged phospholipids, but the dissociation constant
      did not, being about 10(-8) M, except that for the interaction with
      phosphatidylinositol, which was one order of magnitude lower. We also found that
      Domain I and Asialo-beta 2-GPI bound to liposome membranes containing negatively
      charged phospholipids, and that in the interaction with cardiolipin, their
      dissociation constants were about 10(-6) and 10(-8) M, respectively. At neutral
      pH and both low and high ionic strengths, the affinities of the nicked forms of
      beta 2-GPI and Asialo-beta 2-GPI for cardiolipin were both lower than those of
      their intact forms but similar to that of Domain I.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8537302
TI  - Thermosensitivity of green fluorescent protein fluorescence utilized to reveal
      novel nuclear-like compartments in a mutant nucleoporin NSP1.
AB  - Tagging proteins with the green fluorescent protein (GFP) from Aequorea victoria
      is a good means of analyzing protein localization in living cells. Nevertheless,
      GFP and a chimeric protein, GFP-nucleoplasmin, expressed in Saccharomyces
      cerevisiae were less fluorescent at high culture temperatures. Proteins
      synthesized at a low temperature retained their fluorescence despite a shift to a
      higher temperature. Hence, when a temperature-sensitive nsp1 mutant expressing
      GFP-nucleoplasmin was cultured at 23 degrees C and then shifted to 35 degrees C,
      we were able to exclusively monitor the localization of the protein synthesized
      prior to the temperature shift. This protein accumulated in novel nuclear-like
      compartments devoid of DNA.

PMID- 8537303
TI  - Detection of protein 3D-1D compatibility characterized by the evaluation of side
      chain packing and electrostatic interactions.
AB  - A new approach to evaluate protein structure (3D)-sequence (1D) compatibility has
      been developed. This approach uses four functions: side-chain packing, solvation,
      hydrogen-bonding, and local structure functions. The side-chain packing function
      takes into account not only inter-residue distance but also inter-residue contact
      and angle. Parameters defining the functions were statistically derived from 101
      proteins with known 3D structures. The functions are combined to give a score
      quantifying the 3D-1D compatibility. The ability to identify the native structure
      of a protein among a large number of incorrect structures was tested. For 69 out
      of the 70 proteins examined, the native structures were successfully identified.
      Particularly, the side-chain packing function showed clear improvement over our
      previous function. The only unsuccessful case was observed for cytochrome c3
      containing four haems; such prosthetic groups were ignored in the calculation. In
      addition to the above functions, two procedures for removing membrane-spanning
      regions and estimating electrostatic interactions were also adopted. A sequence
      for which membrane-spanning regions were predicted was considered incompatible
      with a structure irrespective of the compatibility score. A method to calculate
      the electrostatic interaction energy was developed and used for the detection of
      electrostatically undesirable interactions between residues of a sequence
      threaded onto a structure. These procedures greatly help to remove false
      positives in the 3D-1D compatibility search.

PMID- 8537304
TI  - Enhancement of stress-induced synthesis of stress proteins by mastoparan in C6
      rat glioma cells.
AB  - The levels of two small stress proteins, hsp27 and alpha B crystallin, were low
      in C6 glioma cells confluency. However, the levels of the two proteins increased
      after exposure of cells to heat (42 degrees C for 30 min) or arsenite (50-100
      microM for 1 h) stress. When cells were exposed to arsenite or heat in the
      presence of mastoparan, a peptide toxin from wasp venom, the induction of hsp27
      and alpha B crystallin was markedly stimulated, as detected by means of specific
      immunoassays, Western blot analysis, and Northern blot analysis. The response of
      hsp70 to each stress was also enhanced in the presence of mastoparan. Treatment
      of cells with 40 microM mastoparan alone barely induced the accumulation of hsp27
      and alpha B crystallin. The stimulatory effect of mastoparan was little affected
      in cells that had been treated with pertussis toxin, but it was strongly
      suppressed in the presence of quinacrine, an inhibitor of phospholipase A2. These
      results suggest that mastoparan, which is an activator of phospholipase A2,
      enhances the responses to stress of hsp27, alpha B crystallin and hsp70 by
      increasing the metabolic activity of the arachidonic acid cascade.

PMID- 8537305
TI  - Structure of the gene encoding mouse reticulocalbin, a novel endoplasmic
      reticulum-resident Ca(2+)-binding protein with multiple EF-hand motifs.
AB  - Reticulocalbin, an endoplasmic reticulum (ER)-resident Ca(2+)-binding protein, is
      a member of the EF-hand Ca(2+)-binding protein superfamily [Ozawa, M. and
      Muramatsu, T. (1993) J. Biol. Chem. 268, 699-705]. Reticulocalbin has six repeats
      of a domain containing the EF-hand motif. In addition, the protein has an amino
      terminal leader sequence which serves as a signal for transfer of the protein
      into the lumen of the ER, and a His-Asp-Glu-Leu sequence at its carboxy terminus
      which functions as a signal to retain the protein in the ER. In this paper, we
      describe the genomic structure of this unique Ca(2+)-binding protein. Southern
      blot analysis of mouse genomic DNA revealed that there is a single copy of the
      reticulocalbin gene per haploid genome. The gene spans over 13 kilobase pairs and
      encodes six separate exons. Thus, reticulocalbin differs from the cytosolic
      Ca(2+)-binding protein calbindin D28 which also has six EF-hand motif domains,
      but the gene for which is divided into 11 exons. While there is some correlation
      between exon division and protein domain structure, these relationships are not
      as clear as they are in other genes. Comparison of the gene organization of
      reticulocalbin with that of other EF-hand proteins revealed that reticulocalbin
      diverged very early from other members of the EF-hand protein super-family.

PMID- 8537306
TI  - Zn(2+)-mediated domain-domain communication in human erythrocyte band 3.
AB  - Zn2+ could inhibit the anion transport activity of spectrin-stripped inside-out
      human erythrocyte membrane vesicles (IOVs). Removal of the cytoplasmic domain
      from Band 3 by trypsin could eliminate Zn2+ inhibition. The location of a Zn(2+)
      binding site was confirmed by atomic absorbance spectrometry. The results of time
      resolved fluorescence and intrinsic fluorescence quenching by KI and hypocrellin
      B (a photosensitive pigment obtained from a parasitic fungus growing in Yunnan,
      China) showed that the cytoplasmic domain is necessary for the Zn(2+)-induced
      conformational changes of the whole molecule as well as the membrane domain of
      Band 3. It is suggested that Zn2+ induced a conformational change in the
      cytoplasmic domain of Band 3, which in turn was transmitted to the membrane
      domain, resulting in an inhibition of activity of Band 3. Such long-range
      conformational changes may imply that the cytoplasmic domain is poised to
      function as a cytosolic arm in order to modulate the structure of the membrane
      domain of Band 3.

PMID- 8537307
TI  - Expression of rat cathepsin D cDNA in Saccharomyces cerevisiae: implications for
      intracellular targeting of cathepsin D to vacuoles.
AB  - To investigate the intracellular transport mechanisms of lysosomal cathepsin D in
      yeast cells, we produced cathepsin D in Saccharomyces cerevisiae by placing the
      coding region under the control of the promoter of the yeast glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) gene. Immunoblotting analysis by the use of an
      antibody specific for rat cathepsin D coding sequence produced an intermediate
      species which had a slightly higher molecular weight than that of the mature
      cathepsin D. Cell fractionation experiments demonstrated that the cathepsin D
      polypeptide was colocalized to the yeast vacuoles with the marker enzyme
      carboxypeptidase Y in a Ficoll step gradient. A biosynthesis study with pulse
      chase kinetic analysis revealed that the precursor polypeptide was accurately
      sorted to the yeast vacuoles as determined by cell fractionation, and that N
      linked carbohydrate modifications were not required for vacuolar sorting of this
      protein. To elucidate the role of the propeptide region of cathepsin D, which
      might function in the intracellular targeting to the vacuole, a deletion mutant
      of cathepsin D lacking the propeptide was prepared and its intracellular
      targeting was examined after transfection into yeast cells. Immunoblotting
      analysis demonstrated that the propeptide-deleted mutant protein was recovered in
      a low quantity as compared with that in the case of yeast cells expressing the
      wild-type protein in the isolated vacuolar fraction. Immunofluorescence analysis
      revealed that the deletion mutant protein appeared to be accumulated within the
      intracellular small vesicles but not in the carboxypeptidase Y-positive vacuoles.
      Overall, these results indicate that the rat cathepsin D precursor polypeptide is
      recognized by mechanisms similar to those involved in the intracellular sorting
      of vacuolar proteins through the ER/Golgi/vacuolar sorting pathway in yeast
      cells, and that the propeptide has an important function in translocation of the
      cathepsin D polypeptide to the vacuole.

PMID- 8537308
TI  - An anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody recognized the
      third Kunitz domain (K3) of free-form TFPI but not lipoprotein-associated forms
      in plasma.
AB  - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor with
      three tandem inhibitory domains, which inhibits the initial reactions of the
      extrinsic blood coagulation pathway through the first and second Kunitz domains.
      We prepared a monoclonal antibody against recombinant human TFPI (rTFPI) and
      determined the epitope as the third Kunitz domain, using fragments derived from
      rTFPI (K1-K2 fragment and K3 fragment) and synthetic peptides. We then developed
      an enzyme immunoassay (EIA) method using a combination of the monoclonal antibody
      and a polyclonal antibody. Although TFPI activity is distributed among LDL/VLDL
      associated, HDL-associated, and free forms of TFPI after gel-filtration of human
      plasma, only the free form was detected by the EIA method. After incubation with
      LDL, the antigenicity of rTFPI was reduced, but that of K3 fragment was not. Gel
      filtration analysis of the mixture of radiolabeled rTFPI or K3 with LDL
      demonstrated that rTFPI, but not K3, bound LDL. From these results, we concluded
      that the monoclonal antibody against TFPI recognized only a free form of TFPI in
      plasma, since the epitope of lipoprotein-associated TFPI had been masked by the
      interaction with lipoproteins.

PMID- 8537309
TI  - Amino acid sequences of trypsin inhibitors from the melon Cucumis melo.
AB  - Two squash family trypsin inhibitors, CMeTI-A and CMeTI-B, were isolated from the
      melon (Cucumis melo) seeds, by ion exchange chromatography, gel filtration,
      affinity chromatography, and high-performance liquid chromatography, and their
      amino acid sequences were determined. All inhibitors contain 29 amino acid
      residues including 6 half-cystine residues. They differ by twelve amino acid
      residues. These polypeptides are strong inhibitors of bovine trypsin, with Ki
      values of 1.6 x 10(-10) M (CMeTI-A) and 4.7 x 10(-10) M (CMeTI-B). The products
      of CMeTI-A and CMeTI-B cleaved at their reactive sites by tryptic digestion
      during the purification by trypsin-Sepharose 4B affinity column chromatography
      are active against trypsin activity, but a molar ratio of inhibitor to trypsin of
      2:1 for trypsin-treated CMeTI-B or 1:1 for trypsin-treated CMeTI-A is required.

PMID- 8537310
TI  - Drosophila melanogaster aldolase: characterization of the isozymes alpha, beta,
      and gamma generated from a single gene.
AB  - Three isozymic forms, alpha, beta, and gamma, of Drosophila melanogaster aldolase
      are produced from a single gene by alternative usage of the triple exons 4 (4
      alpha, 4 beta, and 4 gamma) [Shaw-Lee et al. (1992) J. Biol. Chem. 267, 3959
      3967; Kim et al. (1992) Mol. Cell. Biol. 12, 773-783; Kai et al. (1992) J.
      Biochem. 112,677-688]. The expression plasmids for the respective isozymes were
      transfected into Escherichia coli cells, and the isozymes alpha and beta were
      purified to homogeneity by a simple procedure, though isozyme gamma was only
      partially purified. These isozymes are active towards two substrates, fructose
      1,6-bisphosphate (Fru-1,6-P2) and fructose-1-phosphate (Fru-1-P), with a
      preference for Fru-1,6-P2 over Fru-1-P, but they have different kcat/Km values
      towards these two substrates; isozyme alpha shows the highest value for Fru-1,6
      P2. These isozymes show similarity in optimal pHs, thermal stability, and Km
      values for both Fru-1,6-P2 and Fru-1-P. They are composed of four identical
      subunits of 40 kDa, forming a tetramer with a molecular weight of approximately
      160 kDa. The three isozymes are different in primary structure only at the
      carboxyl-terminal region encoded by the respective exon 4. Therefore, this region
      should be primarily responsible for the distinct characteristics of these
      isozymes.

PMID- 8537311
TI  - Citrate synthase purified from Tetrahymena mitochondria is identical with
      Tetrahymena 14-nm filament protein.
AB  - A 14-nm filament protein (designated as 49K protein) was purified from a ciliated
      protozoan, Tetrahymena, using the polymerization and depolymerization procedure.
      Previous studies in our laboratory showed that its primary structure shared a
      high sequence identity with citrate synthases known so far and that the 49K
      protein possessed citrate synthase activity. To ascertain whether or not
      Tetrahymena's mitochondrial citrate synthase is identical to the 49K protein,
      citrate synthase was purified from Tetrahymena mitochondria using ammonium
      sulfate fractionation, Butyl-Toyopearl and SP-Toyopearl column chromatographies,
      based on monitoring of the enzymatic activity. The molecular weight of the
      purified citrate synthase was estimated to be 49 kDa, as was that of the 49K
      protein and the enzyme cross-reacted with an anti-49K protein antiserum. The
      purified citrate synthase showed much the same optimum pH, optimum KCl
      concentration, effects of substrate concentrations (acetyl-CoA and oxaloacetate),
      and inhibitory effect by ATP as those of purified 49K protein. Furthermore, an
      anti-49K protein monoclonal antibody strongly suppressed the enzymatic activity
      of the purified citrate synthase. Thus, we suggest that mitochondrial citrate
      synthase and the 49K protein are identical and that the 49K protein has dual
      functions in the cytoskeleton in cytoplasm and as a TCA cycle enzyme, citrate
      synthase, in mitochondria.

PMID- 8537312
TI  - Synthesis of pyridine nucleotide analogs using rabbit spleen pyridine nucleotide
      glycohydrolase and stereospecificity of the transglycosidation reaction.
AB  - Seven pyridine nucleotide analogs were synthesized, including nicotinic acid
      mononucleotide, nicotinic acid-adenine dinucleotide, and nicotinic acid-adenine
      dinucleotidephosphate, by means of the transglycosidase activity of rabbit spleen
      pyridine nucleotide glycohydrolase. The velocity ratio of the transglycosidation
      to the hydrolysis in the presence of 16 mM nicotinamide mononucleotide and 0.3 M
      nicotinic acid at pH 5.2 was greater than 10 and the
      transglycosidation/hydrolysis partition ratio was estimated to be (12 +/- 2) x
      10(3). The partition ratio values obtained with 3-acetylpyridine and
      nicotinylglycine were smaller than that with nicotinic acid. Configurational
      analysis of pyridinium C-N glycosidic linkages of the transglycosidation products
      by means of 1H-NMR, UV, CD, and paper chromatography indicated that the
      configuration was completely retained and absolutely beta. Retention of the
      configuration, together with the substrate specificity of the enzyme for the beta
      pyridinium linkage and formation of the intermediary enzyme-phosphoribosyl (or
      ADP-ribosyl) complex during the enzyme catalysis, indicated that the
      transglycosidation reaction catalyzed by the enzyme proceeds through the double
      replacement mechanism.

PMID- 8537313
TI  - Primary structure of N-acyl-D-glutamate amidohydrolase from Alcaligenes
      xylosoxydans subsp. xylosoxydans A-6.
AB  - The gene coding the N-acyl-D-glutamate amidohydrolase of Alcaligenes xylosoxydans
      subsp. xylosoxydans A-6 (Alcaligenes A-6) was cloned and its complete DNA
      sequence was determined. The N-acyl-D-glutamate amidohydrolase structural gene
      consists of 1,464 nucleotides and encodes 488 amino acid residues. The molecular
      weight of the enzyme was calculated to be 51,490. This value is close to the
      apparent molecular weight of 59,000 determined for the purified enzyme from
      Alcaligenes A-6 by sodium dodecyl sulfate (SDS) polyacrylamide gel
      electrophoresis (PAGE). The N-terminal amino acid sequence of the recombinant
      protein exactly matches the amino acid sequence derived from the DNA sequence and
      that determined from the Alcaligenes A-6 enzyme (NH2-MQEKLDLVIEGGWVIDGLGG). The
      deduced amino acid sequence of the cloned N-acyl-D-glutamate amidohydrolase
      showed high sequence homology with those of N-acyl-D-aspartate amidohydrolase
      (46%) and D-aminoacylase (47%) from Alcaligenes A-6. This fact strongly suggests
      that these three enzymes have evolved from a common ancestral gene.

PMID- 8537314
TI  - cDNA sequencing and expression of rat mast cell tryptase.
AB  - A cDNA encoding rat mast cell tryptase (rMCT) was successfully cloned, and
      sequenced, from peritoneal cells of Lewis rats infected with Nippostrongylus
      brasiliensis by the reverse transcription-polymerase chain reaction and rapid
      amplification of cDNA ends methods. The cDNA was 1,097 base-pairs long, and
      included 822 base-pairs of an open reading frame. As judged from the deduced
      amino acid sequence, rMCT is highly homologous to mouse mast cell protease-6, and
      is considered to be translated as a prepro-enzyme with a 19-amino acid signal
      peptide, a 10-amino acid activation peptide, and a 245-amino acid mature enzyme.
      The rMCT mRNA was not detected in peritoneal cells of mast cell-deficient Ws/Ws
      rats, though it was strongly detected in ones of littermate +/+ and Lewis rats.
      In addition to in peritoneal mast cells, the rMCT mRNA was detected in the
      tongue. However, mRNA signals were not detected in the small intestine regardless
      of N. brasiliensis infection. Nor were mRNA signals detected in RBL2H3 rat
      basophilic leukemia cells. In the lung, the rMCT mRNA was strongly detected after
      infection with N. brasiliensis, though it was only faintly detected before
      infection. These results suggest that the rMCT is basically specific for
      connective tissue mast cells, but not for mucosal mast cells and that it is up
      regulated in the lung during the inflammatory process of a parasitic infection.

PMID- 8537315
TI  - Isolation of thermolabile mutant RNA polymerase II from fission yeast
      Schizosaccharomyces pombe with mutations in the subunit 3 gene.
AB  - Subunit alpha of prokaryotic RNA polymerases plays key roles in protein-protein
      contacts for both subunit assembly and transcription activation. To gain an
      insight into the roles of subunit 3, the eukaryotic homologue of alpha,
      temperature-sensitive mutants of the fission yeast, Schizosaccharomyces pombe,
      have been isolated after transformation of the mutagenized rpb3 gene encoding
      mutant subunit 3 of RNA polymerase II. A total of 68 ts mutants were classified
      into two groups: mutants comprising one group ceased growing immediately after a
      temperature up-shift, while mutants comprising the other group exhibited delayed
      growth arrest at high temperatures. RNA polymerase II partially purified from
      Ts54, one of the group 2 mutants, was thermolabile in vitro, as measured by a non
      specific transcription assay. This mutant carries double mutations in domain A of
      subunit 3, and thus can be used as a reference mutant of RNA polymerase II.

PMID- 8537316
TI  - Morphology of ras-transformed cells becomes apparently normal again with tyrosine
      kinase inhibitors without a decrease in the ras-GTP complex.
AB  - Radicicol, an inhibitor of protein-tyrosine kinase, was found to cause
      morphological reversion of v-Ha-ras-transformed NIH3T3 fibroblasts and T24 human
      urinary bladder carcinoma cells that contain an activated ras mutation. The
      network of actin stress fibers was restored during the treatment with radicicol.
      A similar morphological change was observed with another protein-tyrosine kinase
      inhibitor, herbimycin A. Radicicol did not cause any changes in the proportion of
      the active GTP binding form of p21ras or its subcellular localization. These
      results rule out the possibility that the morphological reversion by radicicol is
      due to direct or indirect inhibition of the p21ras function. Cycloheximide and
      actinomycin D inhibited the morphological change by radicicol, suggesting that
      the induced transcription of a gene(s) followed by de novo protein synthesis is
      required for suppression of the transformed phenotype in ras-transformed cells by
      tyrosine kinase inhibitors.

PMID- 8537317
TI  - Purification and characterization of thrombopoietin.
AB  - A thrombopoietic factor, termed thrombopoietin (TPO), was highly purified
      directly from the plasma of sublethally irradiated 1,100 rats by measuring the
      production of megakaryocytes from a highly enriched population of rat
      megakaryocyte progenitor cells (CFU-MK). The rat plasma TPO is a glycoprotein and
      strongly hydrophobic. The total activity and purification yields obtained were
      about 29% and 1.49 x 10(8), respectively. The amino acid sequences of the two
      peptide fragments prepared from the purified 19 kDa TPO were analyzed, and used
      for the cloning of rat and human TPO cDNAs. It was found that the 19 kDa TPO was
      truncated but comprised at least 163 amino acids. The sequence of human TPO cDNA
      revealed that the TPO was identical to the c-Mpl ligand. Both rat and human TPOs
      expressed in COS-1 cells exhibited significant activity toward the CFU-MK in
      vitro, and were active in stimulating platelet production in mice. These results
      indicate that a thrombopoietic factor originally found in the irradiated rat
      plasma is a ligand for the rat c-Mpl.

PMID- 8537318
TI  - Iron-regulated expression and membrane localization of the magA protein in
      Magnetospirillum sp. strain AMB-1.
AB  - The magA gene from Magnetospirillum sp. strain AMB-1 is required for the
      synthesis of bacterial magnetic particles (BMPs). This gene has been cloned,
      sequenced and found to encode a protein which is homologous to the Escherichia
      coli potassium efflux membrane-binding protein, KefC. By using the firefly
      luciferase gene (luc) cloned downstream of the magA promoter, the effect of iron
      on regulation of magA expression was investigated, and transcription of magA was
      found to be enhanced by low concentrations of iron. Intracellular localization of
      the MagA protein was studied using magA-luc fusion proteins. The luc gene was
      cloned downstream of the magA hydrophilic C-terminal domain. Detection of
      luciferase activity in the cytoplasm, cell membrane, and magnetic particle
      membrane subcellular fractions confirmed that the MagA fusion protein was
      localized in the cell membrane. The fusion protein was also detected on the
      surface of the lipid bilayer covering the magnetic particles. These results
      suggest that MagA is a membrane-bound protein, the expression of which is
      enhanced at low iron concentrations.

PMID- 8537319
TI  - Lymphocyte isoforms of mouse p50 LSP1, which are phosphorylated in mitogen
      activated T cells, are formed through alternative splicing and phosphorylation.
AB  - p50 is phosphorylated in mitogen-stimulated T cells, and translocated from the
      membrane to the cytosol after activation of protein kinase C. Sequence analysis
      of p50 revealed that it is identical with LSP1, a putative calcium-binding and
      actin-binding protein. lymphocyte form of p50 exhibits heterogeneity in the
      apparent molecular mass on SDS-PAGE, 50 and 52 kDa (pp50 and pp52), and each
      isoform exhibits heterogeneity in the isoelectric point, when examined by two
      dimensional PAGE. When the two molecular mass variants of p50 were
      dephosphorylated with alkaline phosphatase, both isoforms showed the same
      apparent molecular mass of 50 kDa on SDS-PAGE, but could be distinguished by
      their distinct isoelectric points. Dephosphorylated pp50 (p50a) has an acidic pI
      compared with dephosphorylated pp52 (p50b). Comparison of the peptide maps of
      purified p50a and p50b on HPLC revealed that the difference was limited to one
      peptide peak. NH2-terminal sequence and mass spectrometric analyses of these
      peptides showed that the peptides derived from p50a and p50b had the same NH2
      terminal amino acid sequence up to eight residues, but had distinct molecular
      masses, 5,533.4 and 6,318.6 Da, respectively. These data suggested that pp52
      (p50b) is the product of the previously cloned cDNA and the reduction in the
      molecular mass of the p50a-derived peptide could be explained by deletion of six
      amino acid residues, EHLIRH or HLIRHQ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537320
TI  - A novel DNA binding protein that recognizes the methylated c-Myc binding motif.
AB  - We detected a novel nuclear protein, MMBP-3, that bound to the c-Myc binding
      motif (CACGTG) in which deoxycytidine in the CpG sequence was methylated. MMBP-3
      was partially purified by chromatography on heparin-agarose and hydroxyapatite,
      followed by affinity adsorption to a matrix coupled to the methylated binding
      motif. Its binding to the methylated c-Myc binding motif was specific, although
      it also recognized the unmethylated motif weakly. MMBP-3 was further found to
      recognize only one of two differently hemimethylated forms of the double-stranded
      c-Myc binding motif. MMBP-3 activity was detected in proliferating C2C12 and
      C3H/10T1/2 cells, and down regulated when the growth of these cells was
      inhibited. We propose that MMBP-3 plays a role in regulating the c-Myc function
      by recognizing the methylation state of the c-Myc binding motif in a growth
      dependent manner.

PMID- 8537321
TI  - Comparison of reactivity of monoclonal antibody (3F2) to trimeric tumor necrosis
      factor (TNF-alpha) with that to monomeric TNF-alpha.
AB  - Biologically active TNF-alpha is a trimer. Our newly developed monoclonal
      antibody against recombinant human TNF-alpha (3F2) bound to TNF-alpha immobilized
      on a solid phase precoated with the same monoclonal antibody, 3F2. We therefore
      examined the possibility that 3F2 preferentially recognized trimeric TNF-alpha,
      and obtained the following results. (i) Treatment of TNF-alpha with 1% NP40
      enhanced the dissociation from the trimer to the monomer. The treatment also
      reduced the reactivity of 3F2 to TNF-alpha immobilized on a solid phase precoated
      with either 3F2 or a rabbit anti-TNF-alpha antibody (PT50). (ii) When trimeric
      and monomeric TNF-alpha, obtained by gel filtration of NP40-treated TNF-alpha,
      were assayed with either PT50 (solid phase)/3F2 (fluid phase) or PT50/PT50,
      PT50/3F2 showed a higher response to trimeric TNF-alpha than to monomeric TNF
      alpha, while PT50/PT50 showed the opposite result. (iii) The values for two
      fractions containing only trimeric TNF-alpha obtained on ELISA with PT50/3F2
      fitted the standard curve for ELISA with PT50/3F2 which was made by using
      unseparated TNF-alpha. Taken together, these findings suggested that 3F2
      preferentially recognizes trimeric TNF-alpha.

PMID- 8537322
TI  - Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk
      or Lyn alone is not sufficient to prevent radiation-induced apoptosis.
AB  - Radiation-induced biochemical events that mediate the intracellular signal
      transduction leading to cell apoptosis are largely unknown. Limited evidence
      suggests the possible involvement of one or more protein-tyrosine kinases (PTKs)
      in radiation-induced cellular responses, including apoptosis. However, so far, a
      PTK(s) responsible for the radiation-induced tyrosine phosphorylation of cellular
      substrates has not been identified and the role of the PTK(s) in the radiation
      induced apoptosis remains unclear. To examine the roles of Syk and Lyn in
      radiation-induced signal transduction and radiation-induced apoptosis, we
      analyzed Syk-deficient or Lyn-deficient DT40 B cells along with wild-type cells
      following radiation. When DT40 B cells were exposed to radiation, the activity of
      Syk kinase dramatically increased and reached a maximum with 0.25 Grays (Gy) (15
      s), and then decreased, whereas Lyn kinase activity increased and reached a
      maximum with a dose of 1.00 Gy (1 min). However, an apparent difference was not
      observed in radiation-induced apoptosis among wild-type, Syk-deficient, and Lyn
      deficient DT40 B cells. These results indicate that Syk and Lyn kinases are
      involved in radiation-induced signal transduction, with different kinetics. In
      addition, our results revealed that functional inactivation of Syk or Lyn alone
      is not sufficient to prevent radiation-induced apoptosis. Thus, it is suggested
      that the activation of Syk or Lyn kinase alone may be sufficient to mediate the
      radiation-induced apoptosis in DT40 B cells, or both kinases may not be required
      for this biological process.

PMID- 8537323
TI  - Cloning and sequence of the SCS2 gene, which can suppress the defect of INO1
      expression in an inositol auxotrophic mutant of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae ire15 mutant has a defect in the expression of INO1,
      showing the inositol auxotrophic phenotype [Nikawa, J. (1994) Gene 149, 367-372].
      We have isolated five yeast genes which suppress the ire15 mutation in multiple
      copies by genetic complementation. Among them, one gene, designated as SCS2, also
      suppressed the choline-sensitive dominant mutation, CSE1 [Hosaka, K. et al.
      (1992) J. Biochem. 111, 352-358]. The CSE1 mutation is not allelic to ire15.
      Sequencing analysis revealed that the SCS2 gene encodes 244 amino acid residues
      with a calculated molecular mass of 26,866. INO2/SCS1, which is another
      suppressor gene for CSE1 and is known to be a positive factor for INO1
      expression, also suppressed the growth defect of the ire15 mutant. These results
      clearly indicate that the ire15 and CSE1 mutations genetically interact and the
      SCS2 and INO2/SCS1 genes are involved in the regulation of INO1 expression.

PMID- 8537324
TI  - Alteration in the reactivity of sphingomyelin in mitogen-stimulated lymphocytes.
AB  - The antigens for a monoclonal antibody, VJ-41, established by alloimmunization of
      B10.A(3R) mice with lymphocytes from B10.A(5R) mice and screening of its
      reactivity toward Con A-stimulated human T lymphocytes, were found to be
      phosphorylcholine-containing ceramides (sphingomyelin) and disaturated fatty acyl
      glycerol (phosphatidyl-choline, PC), but neither deacylated sphingomyelin nor
      unsaturated fatty acid-containing PC reacted with the antibody. Although the
      reactivity of disaturated fatty acyl PC increased with increasing chain length,
      that of sphingomyelin was stronger than that of di-20:0-PC. The binding of the
      antibody to Con A-stimulated lymphocytes was inhibited by sphingomyelin
      containing liposomes, but not by di-18:0-PC-containing ones, and the
      concentration of sphingomyelin in Con A-stimulated human T-lymphocytes was the
      same as that in non-stimulated ones, indicating that the reactivity of
      sphingomyelin in lymphocytes is altered by Con A-stimulation.

PMID- 8537325
TI  - Intracellular sorting of lysosomal beta-glucuronidase is altered due to
      administration of dibutyl phosphate.
AB  - Organophosphate compounds are known to cause a selective increase of beta
      glucuronidase activity in rat serum. Previous data suggested that increase of
      serum beta-glucuronidase activity was well correlated with decrease of that
      activity in rat liver microsomal fraction, thereby, suggesting a role of the
      microsomal enzyme in mediating the organophosphate effect. To investigate further
      the intracellular sorting pathway of beta-glucuronidase in dibutyl phosphate
      treated rats, liver subcellular fractions were prepared at 12 or 48 h after in
      vivo administration of [3H]leucine and it was established that microsomal beta
      glucuronidase was the origin of the increased serum enzyme. To characterize the
      intracellular secretory pathway of beta-glucuronidase in dibutyl phosphate
      treated rats, Golgi subfractions were isolated and a time course study was
      carried out. At 30 min after administration of dibutyl phosphate, specific
      activity of beta-glucuronidase in GF-2 (Golgi intermediate fraction) and GF-3
      (Golgi heavy fraction) was significantly increased to the maximum. Furthermore,
      colchicine pretreatment of rats caused a delay of the peak of specific activity
      for 30 min in GF-2 and GF-3, and accumulation of enzyme activity in Golgi
      subfractions was observed. Colchicine pretreatment also had an inhibitory effect
      on release of beta-glucuronidase into serum until 30 min after dibutyl phosphate
      injection. The electrophoretic pattern of microsomal beta-glucuronidase on
      polyacrylamide gel was found to show two major bands of microsomal enzyme type
      and lysosomal enzyme type in dibutyl phosphate-treated rats. Taken together,
      these findings indicate that microsomal beta-glucuronidase follows the
      intracellular secretory pathway and is secreted into serum via Golgi complex in
      response to dibutyl phosphate.

PMID- 8537326
TI  - Biochemical characterization of liver microsomal, Golgi, lysosomal, and serum
      beta-glucuronidases in dibutyl phosphate-treated rats.
AB  - Organophosphate compounds are known to cause the selective release of rat liver
      microsomal beta-glucuronidase into plasma. To investigate the alterations of
      molecular forms and oligosaccharide moieties of liver beta-glucuronidase in
      organophosphate compound-administered rats, beta-glucuronidase was isolated from
      microsomal, Golgi, lysosomal, and serum fractions. In SDS-polyacrylamide gel
      electrophoresis, a single polypeptide band was observed on gels in Golgi and
      serum beta-glucuronidases. This result indicated that Golgi and serum beta
      glucuronidases of treated rats did not undergo post-translational proteolytic
      processing, in contrast to those in control rat livers. Biochemical
      characterization of the isolated beta-glucuronidases by employing lectin affinity
      chromatography revealed that interaction of serum and Golgi enzymes with Ricinus
      communis agglutinin- and wheat germ agglutinin-Sepharose was fairly strong, and
      that microsomal and lysosomal enzymes were poorly retained on those columns.
      These results suggested that the serum and Golgi beta-glucuronidases are
      sialoglycoproteins. A clearance study also showed that infused serum beta
      glucuronidase was slowly cleared from plasma with a half-life of about 60 min,
      but the asialo-serum enzyme was rapidly cleared with a half-life of about 5 min.
      These results imply that microsomal beta-glucuronidase undergoes extensive
      modification of the oligosaccharide moieties by terminal glycosyltransferases at
      the trans Golgi when it is destined for secretion into serum in response to
      treatment with an organophosphate compound.

PMID- 8537327
TI  - Production of hetero-dimeric dihydrofolate reductase-thymidylate synthase
      bifunctional enzyme.
AB  - As a result of the expression of a single open reading frame composed of the
      coding sequence for a cysteine-free mutant (Cys85-->Ala, Cys152-->Ser) of
      Escherichia coli dihydrofolate reductase (DHFR; 18K monomeric protein), that for
      the E. coli thymidylate synthase (TS; dimeric protein with a 30K promoter), and a
      spacer sequence (coding 7 amino acids) with a Shine-Dargarno sequence, an active
      hetero-dimeric bifunctional enzyme with 50K DHFR-TS and 30K TS polypeptides was
      stably produced in the transformed E. coli cell in addition to an overproduction
      of the TS dimeric enzyme. The highly purified hetero-dimeric enzyme has similar
      Vmax and Km values in both DHFR and TS activities to those of the natural
      counterparts, monomeric DHFR and dimeric TS. Although the hetero-dimeric enzyme
      did not show an apparent channeling transfer of dihydrofolate (the intermediate
      substrate) between the spatially discrete DHFR and TS active sites, the coupling
      efficiency of the TS and DHFR reactions in the artificial enzyme was better than
      that in the separated enzymes, as shown by a decrease in the intermediate
      concentration at the steady state in the coupled reaction.

PMID- 8537328
TI  - Effect of site-directed mutations on processing and activity of gamma
      glutamyltranspeptidase of Escherichia coli K-12.
AB  - gamma-Glutamyltranspeptidase [EC 2.3.2.2] of Escherichia coli K-12 is thought to
      be synthesized from a single precursor polypeptide into a heterodimeric form
      through post-translational processing. Cells of a gamma-glutamyltranspeptidase
      overproducing transformant of E. coli K-12 were fractionated and the localization
      of the enzyme was examined by Western blot analysis. The periplasmic fraction
      only contained the mature form of gamma-glutamyltranspeptidase, membrane fraction
      only contained the precursor of gamma-glutamyltranspeptidase, and no precursor of
      gamma-glutamyltranspeptidase was detected in the cytoplasmic fraction. Amino acid
      residues at the cleavage site for processing into the large and small subunits
      were substituted by site-directed mutagenesis. The processing phenotypes of six
      mutants were examined by Western blot analysis, and their gamma
      glutamyltranspeptidase activities were measured. Mutations at the N-terminal
      amino acid residues of the small subunit (Thr-391, Thr-392, and His-393)
      prevented the maturation of the enzyme and the immature mutants exhibited no
      enzymatic activity. A mutation at the C-terminal residue of the large subunit
      (Gln-390) had less effect on the processing and enzymatic activity. These results
      suggest that the sequence of threonyl-threonyl-histidinyl residues at the N
      terminal of the small subunit is very important for the processing of E. coli K
      12 gamma-glutamyltranspeptidase and this processing is essential to the
      expression of gamma-glutamyltranspeptidase activity of E. coli K-12.

PMID- 8537329
TI  - Proteolytic processing of human protein C in swine mammary gland.
AB  - Maturation of human Protein C (HPC) precursor to a zymogen in the liver requires
      endoproteolytic cleavages after a basic dipeptide, Lys-2-Arg-1 in the propeptide
      and Lys156-Arg157 connecting the light and heavy chain. Recombinant human Protein
      C (rHPC) was expressed in the mammary gland of transgenic swine and its
      proteolytic processing was monitored. We found that about 10-20% of rHPC purified
      from the milk still retained the propeptide and 30-40% was in the single-chain
      form, indicating inefficient proteolytic cleavage. This demonstrates that
      endoprotease(s) of the swine mammary epithelial cells do not process fully the
      precursor of heterologous protein. rHPC was fractionated by anion exchange
      chromatography and polypeptides with novel N-termini at positions -1,152 and 157
      were detected in addition to the known N-termini at residues -24, +1, and 158.
      Since rHPC was found to be stable both in milk and after purification, it is
      possible that these new cleavages on the amino side of arginine at dipeptide
      sites Lys-2-Arg-1, Lys151-Arg152, and Lys156-Arg157 could have occurred in the
      mammary gland. Thus, our results suggest that a portion of HPC precursor was
      proteolytically processed in swine mammary gland differently than those in other
      expression systems.

PMID- 8537330
TI  - Midkine (MK) expression in extraembryonic tissues, amniotic fluid, and
      cerebrospinal fluid during mouse embryogenesis.
AB  - Midkine (MK) and pleiotrophin (PTN) constitute a new family of heparin-binding
      growth factors. Extraembryonic membranes and the placenta of the mouse expressed
      MK mRNA at 11.5 days gestation. While the MK mRNA level in extraembryonic
      membranes decreased during embryogenesis, that in the placenta remained
      unchanged. Immunohistochemical studies showed that Mk was located in the yolk sac
      and in the amnion at 11.5 days gestation. PTN mRNA expression was weak in
      extraembryonic membranes and was scarcely detectable in the placenta. Western
      blot analysis revealed the presence of MK in amniotic fluid and cerebrospinal
      fluid, in amounts of more than 1 microgram/ml, raising the possibility that MK
      delivered by these fluids participates in the regulation of organogenesis.
      Transport of MK from the site of its synthesis appears to also occur in the adult
      kidney, since MK mRNA and the MK protein are localized in different regions of
      the kidney.

PMID- 8537331
TI  - Identification of Fourier transform infrared signals from the non-heme iron in
      photosystem II.
AB  - Fourier transfer infrared (FTIR) signals originating from a high-potential
      electron acceptor in PS II were studied by flash-induced FTIR difference
      spectroscopy. Redox titration of these signals using ferri-ferrocyanide mixtures
      showed midpoint potentials (Em) of 489 +/- 12 and 426 +/- 9 mV at pH 5.5 and 6.5,
      respectively, revealing a pH dependence of about -60 mV/pH unit. These Em values
      and pH dependence were in good agreement with those of the non-heme iron, so
      called Q400, located between QA and QB. This indicates that the observed FTIR
      signals are due to changes in ligands of the non-heme iron and surrounding
      protein moieties induced on photoreduction from Fe3+ to Fe2+.

PMID- 8537332
TI  - Restricted expression of Xenopus midkine gene during early development.
AB  - Midkine (MK) is a heparin-binding growth factor and forms a novel protein family
      together with another member, pleiotrophin (PTN)/heparin-binding growth
      associated molecule (HB-GAM). A cDNA clone isolated from Xenopus laevis specifies
      for the Xenopus counterpart of MK (XMK), and the mode of XMK expression was
      studied by in situ hybridization and Northern blot analysis. XMK was first
      expressed at stage 11 (middle gastrula) and was located in the neural anlage at
      stage 12 (late gastrula). Through stage 13 to 15 (early neurula), XMK expression
      was restricted to the neural folds. At stage 23 (tailbud stage), XMK was
      predominantly localized in the brain and neural tube. At the larva stage, XMK
      expression was again restrictedly observed in the brain, the optic vesicles, the
      otic vesicle, and the spinal cord, all of which are derivatives of the neural
      tube, as well as in the branchial arches, derivatives of the cranial neural
      crest. Comparing the mode of MK expression between Xenopus and the mouse, we
      propose that MK plays evolutionally conserved roles in neurogenesis and
      development of the craniofacial architecture of ectomesenchymal origin. We also
      found that XMK was expressed in various adult organs; strong expression was
      observed in the brain, the eye and the spinal cord, all of which showed intense
      MK expression at the larva stage.

PMID- 8537334
TI  - Nerve growth factor-induced growth arrest and induction of p21Cip1/WAF1 in NIH
      3T3 cells expressing TrkA.
AB  - Treatment of NIH-3T3 cells expressing human TrkA with nerve growth factor (NGF)
      resulted in a rapid cessation of growth. Cells stopped dividing within 24 h of
      NGF treatment and failed to divide as long as NGF was present, accumulating in
      the G1 stage of the cell cycle. NGF caused a prolonged activation of mitogen
      activated protein kinase relative to EGF. NGF treatment of cells greatly
      increased levels of the p21Cip1/WAF1 protein, an inhibitor of cyclin-dependent
      kinases, without affecting levels of p27KIP1 or p16INK4. Levels of p21Cip1/WAF1
      remained elevated for at least 48 h following NGF addition. EGF had little effect
      on p21Cip1/WAF1 expression in the same parental cells expressing the human EGF
      receptor. NGF treatment of cells completely inhibited the activity of the cyclin
      dependent protein kinases CDK2 and CDK4. Inhibition correlated with a 10-20-fold
      increase in the amount of p21Cip1/WAF1 complexed with CDK2 and CDK4. Levels of
      CDK2 and CDK4 were decreased following NGF treatment of cells; however, levels of
      cyclin E and cyclin D were increased. These data indicate that NGF can induce
      cell cycle arrest of NIH-3T3, perhaps through modulation of p21Cip1/WAF1 levels.
      The data also show that distinct signals are generated by TrkA versus the EGF
      receptor in NIH-3T3 cells.

PMID- 8537333
TI  - JAK2, Ras, and Raf are required for activation of extracellular signal-regulated
      kinase/mitogen-activated protein kinase by growth hormone.
AB  - Protein-tyrosine kinases (PTKs) of the JAK family have been characterized on the
      basis of their ability to mediate the rapid induction of transcription of
      interferon-responsive genes through the stimulation of a class of latent
      cytoplasmic transcription factors known as signal transducers and activators of
      transcription (STATs). STAT activation, which has been described as being Ras
      independent, requires tyrosine phosphorylation, but STAT transactivating activity
      is enhanced by phosphorylation on serine as well, probably by extracellular
      signal-regulated kinase/mitogen-activated protein kinase(s) (ERK/MAPK). STATs can
      be activated upon binding of ligands to receptor PTKs, to G-protein-linked
      receptors, and to cytokine receptors. Whether JAKs are required for the
      activation of signaling pathways other than that leading to STAT activation is
      not known. The binding of growth hormone (GH) to its receptor (GHR) activates
      JAK2 and STATs as well as ERK/MAP kinases. We have used a transient transfection
      system in 293 cells to evaluate the requirement for JAK2 in the activation of
      ERK2/MAPK by GH. We found that JAK2 is required for GH-simulated activation of
      ERK2/MAPK. Employing the transient expression of dominant negative forms of H-Ras
      and Raf-1, we determined that the GHR/JAK2-mediated activation of ERK2/MAPK is
      dependent on both Ras and Raf. Thus, JAK protein-tyrosine kinases may represent a
      common component in the activation of the ERK2/MAPK and STAT signaling pathways,
      which appear to bifurcate upstream of Ras activation but converge with ERK/MAPK
      phosphorylation of STATs.

PMID- 8537335
TI  - Cloning, expression, and chromosomal localization of the human uridine nucleotide
      receptor gene.
AB  - Extracellular ATP and ADP mediate diverse physiological responses in mammalian
      cells, in part through the activation of G protein-coupled P2 purinoceptors. The
      cloning and expression of cDNAs encoding several P2 purinoceptor subtypes have
      enabled rapid advances in our understanding of the structural and functional
      properties of these receptors. The current report describes the isolation of a
      gene from a human genomic library that encodes a protein with the greatest
      similarity to the human P2U purinoceptor, a subtype that is distinguished by its
      ability to be activated by uridine nucleotides as well as adenine nucleotides.
      When expressed in a mammalian cell line, this novel receptor is activated
      specifically by UTP and UDP but not by ATP and ADP. Activation of this uridine
      nucleotide receptor resulted in increased inositol phosphate formation and
      calcium mobilization. Fluorescence in situ hybridization revealed that the gene
      encoding the uridine nucleotide receptor is located in region q13 of the X
      chromosome. Dendrogram analysis of the G protein-coupled P2 purinoceptors and the
      uridine nucleotide receptor indicates that these receptors belong to a family
      that may be more aptly named nucleotide receptors.

PMID- 8537336
TI  - Cloning and functional expression of a human uridine nucleotide receptor.
AB  - In order to isolate new subtypes of P2 purinoceptors, sets of degenerate
      oligonucleotide primers were synthesized on the basis of the best conserved
      segments in the published sequences of the chick brain P2Y/P2Y1 and murine
      neuroblastoma P2U/P2Y2 receptors. Their use in polymerase chain reaction (PCR)
      experiments on human genomic DNA amplified, among other things, a 712-base pair
      sequence, that was used as a probe to screen a human genomic DNA library. Several
      clones corresponding to a single locus were isolated, and the sequence analysis
      revealed an intronless 1095-base pair open reading frame. The deduced amino acid
      sequence is consistent with a G protein-coupled receptor and exhibits 51%
      identity with the human P2Y2 receptor and 35% with the chick P2Y1 receptor. A
      close comparison with the human P2Y2 sequence reveals the conservation of
      histidine 262, arginine 265, lysine 289, and arginine 292, which were reported to
      be involved in nucleotide binding (Erb, L., Garrad, R., Wang, Y., Quinn, T.,
      Turner, J. T., and Weisman, G. A. (1995) J. Biol. Chem. 270, 4185-4188). Northern
      blot analysis detected a 1.8-kilobase messenger RNA in human placenta. The coding
      sequence was inserted in the pcDNA3 vector in order to transfect 1321N1 human
      astrocytoma cells. In cells stably expressing the receptor, UTP and UDP
      stimulated the formation of inositol phosphates with equivalent potency and
      maximal effect, ATP behaved as a partial agonist, and ADP was almost inactive. We
      have thus cloned a new member of the G protein-coupled P2 purinergic receptor
      family, which functionally behaves as a pyrimidinergic receptor.

PMID- 8537337
TI  - The regions of the Fe65 protein homologous to the phosphotyrosine
      interaction/phosphotyrosine binding domain of Shc bind the intracellular domain
      of the Alzheimer's amyloid precursor protein.
AB  - Fe65 is a protein mainly expressed in several districts of the mammalian nervous
      system. The search of protein sequence data banks revealed that Fe65 contains two
      phosphotyrosine interaction (PID) or phosphotyrosine binding (PTB) domains,
      previously identified in the Shc adaptor molecule. The two putative PID/PTB
      domains of Fe65 were used to construct glutathione S-transferase-Fe65 fusion
      proteins. Co-precipitation experiments demonstrated that the Fe65 PID/PTB domains
      interacted with several proteins of apparent molecular mass 135, 115, 105, and 51
      kDa. The region of Fe65 containing the PID/PTB domains was used as a bait to
      screen a human brain cDNA library in yeast by the two-hybrid system. Three
      different cDNA clones were isolated, two of which contain overlapping segments of
      the cDNA encoding the COOH terminus of the Alzheimer's beta-amyloid-precursor
      protein (APP), that represents the short intracellular domain of this membrane
      protein. The third clone contains a cDNA fragment coding for the COOH terminus of
      the human counterpart of a mouse beta-amyloid-like precursor protein. The
      alignment of the three APP encoding cDNA fragments found in the screening
      suggests that the region of APP involved in the binding is centered on the NPTY
      sequence, which is analogous to that present in the intracellular domains of the
      growth factor receptors interacting with the PID/PTB domain of Shc.

PMID- 8537338
TI  - Neoplastic transformation of normal rat embryo fibroblasts by a mutated p53 and
      an activated ras oncogene induces parathyroid hormone-related peptide gene
      expression and causes hypercalcemia in nude mice.
AB  - Parathyroid hormone-related peptide (PTHRP) is a 141-amino acid protein
      identified in various carcinomas associated with humoral hypercalcemia of
      malignancy (HHM). Although the causal role of PTHRP in HHM syndrome has been
      established, the molecular and cellular mechanism by which PTHRP gene is
      overexpressed in certain malignancies remains unknown. We have demonstrated in
      the present study that PTHRP secretion was markedly induced concomitantly with
      the formation of transformed foci after normal rat embryo fibroblasts (REFs) were
      co-transfected with an activated ras (ras) and a mutated form of p53 (p53-mt)
      genes. In either ras- or p53-mt-transfected (nontransformed) cells, only modest
      or barely detectable secretion of PTHRP was observed, respectively. Northern blot
      analysis revealed that PTHRP mRNA was markedly induced in fully transformed cells
      11 days after transfection with both ras and p53-mt genes. Inhibition of RNA
      synthesis with actinomycin D resulted in almost complete disappearance of PTHRP
      mRNA at 2-3 h, suggesting a transcriptional mechanism. Transient transfection
      experiments revealed that PTHRP promoter activity was induced in ras + p53-mt
      transfectants. REFs transformed by ras and p53-mt genes and thereby induced to
      secrete PTHRP in vitro produced aggressively growing tumors associated with HHM
      syndrome when injected into nude mice. These results suggest that activation of
      PTHRP gene is closely related to malignant transformation of normal mammalian
      cells and that ras and p53 may be important regulators of PTHRP gene
      transcription. The transfection-focus formation system of REFs should provide an
      excellent model to study the molecular and cellular mechanism underlying
      concomitant overexpression of PTHRP gene with carcinogenesis.

PMID- 8537339
TI  - Stepwise movement of preproteins in the process of translocation across the
      cytoplasmic membrane of Escherichia coli.
AB  - Derivatives of proOmpA possessing the second cysteine residue at position +302
      and the first one at different positions were constructed at the DNA level. They
      were oxidized to form disulfide-bridged loops of different sizes at different
      positions. In the presence of a protonmotive force, proOmpAs possessing a smaller
      loop could be translocated across the membrane in vitro, whereas ones possessing
      loops comprising more than 16 amino acid residues were hard to translocate. The
      sizes of polypeptide chains that had been translocated and had become protease
      resistant were determined in both the presence and absence of the protonmotive
      force. The size was the same for all proOmpAs possessing the first cysteine
      residue between +244 (proOmpA L59) and +274 (proOmpA L29). When the first
      cysteine residue was moved further away from the N terminus, a sudden increase in
      size, of approximately 30 amino acid residues, was observed, the size being the
      same for proOmpAs possessing the first cysteine residue between +278 (proOmpA
      L25) and +293 (proOmpA L10). The shift in size between proOmpA L29 and proOmpA
      L25 was observed with different proteases exhibiting different substrate
      specificities. Treatment with these proteases resulted in complete digestion of
      SecA on everted membrane vesicles, whereas Sec proteins integrated into membranes
      were considerably resistant to the treatment. These results can be best
      interpreted as that the translocation of preproteins through the secretory
      machinery takes place in every 30 amino acid residues and that SecA is
      responsible for the stepwise movement.

PMID- 8537340
TI  - EPR, electron spin echo envelope modulation, and electron nuclear double
      resonance studies of the 2Fe2S centers of the 2-halobenzoate 1,2-dioxygenase from
      Burkholderia (Pseudomonas) cepacia 2CBS.
AB  - The 2-halobenzoate 1,2-dioxygenase from Burkholderia (Pseudomonas) cepacia 2CBS
      (Fetzner, S., Muller, R., and Lingens, F. (1992) J. Bacteriol. 174, 279-290)
      contains both a ferredoxin-type and a Rieske-type 2Fe2S center. These two
      significantly different 2Fe2S clusters were characterized with respect to their
      EPR spectra, electrochemical properties (Rieske-type cluster with gz = 2.025, gy
      = 1.91, gx = 1.79, gav = 1.91, Em = -125 +/- 10 mV; ferredoxin-type center with
      gz = 2.05, gy = 1.96, gx = 1.89, gav = 1.97, Em = -200 +/- 10 mV) and pH
      dependence thereof. X band electron spin echo envelope modulation and electron
      nuclear double resonance spectroscopy was applied to study the interaction of the
      Rieske-type center of the 2-halobenzoate 1,2-dioxygenase with 14N and 1H nuclei
      in the vicinity of the 2Fe2S cluster. The results are compared to those obtained
      on the Rieske protein of the cytochrome b6f complex (Em = +320 mV) and the water
      soluble ferredoxin (Em = -430 mV) of spinach chloroplasts, as typical
      representatives of the gav = 1.91 and gav = 1.96 class of 2Fe2S centers.
      Properties common to all Rieske-type clusters and those restricted to the
      respective centers in bacterial oxygenases are discussed.

PMID- 8537341
TI  - Extracellular transport of VirG protein in Shigella.
AB  - The ability of Shigella to spread within and between epithelial cells is a
      prerequisite for causing bacillary dysentery and requires the function encoded by
      the virG gene on the large plasmid. The outer membrane VirG (IcsA) protein is
      essential for bacterial spreading by eliciting polar deposition of filamentous
      actin (F-actin) in the cytoplasm of epithelial cells. Recent studies have
      indicated that an N-terminal 80-kDa VirG portion is exposed on the bacterial cell
      surface and released into the external medium, while the following 37-kDa C
      terminal portion is embedded in the outer membrane, although little is known
      about the extracellular transport of the VirG protein. In this study, we
      attempted to elucidate the export pathway of VirG protein across the outer
      membrane and found that the C-terminal 37-kDa portion, termed VirG beta-core,
      serves as the self-transporter for the secretion of the preceding 80-kDa portion
      from the periplasmic side of the outer membrane to the external side. Indeed,
      foreign polypeptides such as MalE or PhoA covalently linked to the N terminus of
      VirG beta-core were transported to the external side of the outer membrane, and
      it was further shown that the folding structure of the passenger polypeptide at
      the periplasmic side of the outer membrane interferes with its translocation.
      Analysis of the secondary structure of VirG beta-core predicted that the critical
      structural property was a beta-barrel channel consisting of amphipathic anti
      parallel transmembrane beta-strands, interspersed by hairpin turns and loops.
      These results thus strongly suggest that the secretion of VirG protein from
      Shigella is similar to the export system utilized by the IgA protease of
      Neisseria.

PMID- 8537342
TI  - Resolution of the aerobic respiratory system of the thermoacidophilic archaeon,
      Sulfolobus sp. strain 7. I. The archaeal terminal oxidase supercomplex is a
      functional fusion of respiratory complexes III and IV with no c-type cytochromes.
AB  - The aerobic respiratory system of the thermoacidophilic archaeon, Sulfolobus sp.
      strain 7, is unusual in that it consists of only a- and b-type cytochromes but no
      c-type cytochromes. In previous studies, a novel cytochrome oxidase a583-aa3
      subcomplex has been purified, which showed a ferrocytochrome c oxidase but no
      caldariellaquinol oxidase activity (Wakagi, T., Yamauchi, T., Oshima, T., Muller,
      M., Azzi, A., and Sone, N. (1989) Biochem. Biophys. Res. Commun. 165, 1110-1114).
      We show here that the cytochrome subcomplex could be copurified with a non-CO
      reactive cytochrome b562 as a novel terminal oxidase "supercomplex," which also
      contained a Rieske-type FeS cluster at gy = 1.89. It contained one copper and all
      four heme centers detectable in the archaeal membranes by the low temperature
      spectrophotometry and the potentiometric titration: cytochromes b562 (+146 mV),
      a583 (+270 mV), and aa3 (+117 and +325 mV). The presence of one copper atom
      indicates that it contains the conventional heme a3-CuB binuclear center for
      reducing molecular oxygen. In conjunction with the presence of a Rieske-type FeS
      center, inhibitor studies suggest that the terminal oxidase segment of the
      respiratory chain of Sulfolobus sp. strain 7 is a functional fusion of
      respiratory complexes III and IV, where cytochrome b562 and the Rieske-type FeS
      center probably play a central role in the oxidation of caldariellaquinol. This
      archaeal terminal oxidase supercomplex reconstitutes the in vitro succinate
      oxidase respiratory chain for the first time together with caldariellaquinone and
      the purified cognate succinate:caldariellaquinone oxidoreductase complex. The
      reconstitution system requires caldariellaquinone for the activity, and is highly
      sensitive to cyanide and 2-heptyl-4-hydroxy-quinoline-N-oxide. These results are
      also discussed in terms of the evolutionary considerations.

PMID- 8537343
TI  - Resolution of the aerobic respiratory system of the thermoacidophilic archaeon,
      Sulfolobus sp. strain 7. II. Characterization of the archaeal terminal oxidase
      subcomplexes and implication for the intramolecular electron transfer.
AB  - The terminal segment of the aerobic respiratory chain of the thermoacidophilic
      archaeon Sulfolobus sp. strain 7 is an unusual caldariellaquinol oxidase
      supercomplex, which contains at least one b-type and three spectroscopically
      distinguishable a-type cytochromes, one copper, and a Rieske-type FeS center. In
      this paper, we report the purification and characterization of two different
      forms of the archaeal a-type cytochromes, namely, a three-subunit cytochrome a583
      aa3 subcomplex and a single-subunit cytochrome aa3 derived from the cytochrome
      subcomplex, in order to facilitate further studies on the terminal oxidase
      segment of Sulfolobus. The optical and EPR spectroscopic analyses suggest the
      presence of two different low-spin heme centers and one high-spin heme center in
      the purified cytochrome a583-aa3 subcomplex, and one low-spin and one high-spin
      hemes in cytochrome aa3, respectively. The Rieske-type FeS center detected in the
      purified cytochrome supercomplex was absent in two forms of the a-type cytochrome
      oxidase, indicating its association with cytochrome b562. The crystal field
      parameters of the lowspin heme a583 center indicate that its axial ligands may be
      similar to those of cytochromes c, rather than conventional bis-histidine
      ligation. In spite of the absence of any c-type cytochrome, a ferrocytochrome c
      oxidase activity was detected in the archaeal purified cytochrome a583-aa3
      subcomplex with no quinol oxidase activity, but not in the purified cytochrome
      oxidase supercomplex, which has been tentatively interpreted as a representative
      of electron transfer from the Rieske FeS center to cytochrome a583 in vivo. Thus,
      our results indicate the following scheme for the intramolecular electron
      transfer of the terminal oxidase supercomplex from Sulfolobus sp. strain 7:
      [caldariellaquinol-->] b562-->Rieske FeS center-->a583 aa3-->molecular oxygen.

PMID- 8537344
TI  - Resolution of the aerobic respiratory system of the thermoacidophilic archaeon,
      Sulfolobus sp. strain 7. III. The archaeal novel respiratory complex II
      (succinate:caldariellaquinone oxidoreductase complex) inherently lacks heme
      group.
AB  - An active respiratory complex II (succinate:quinone oxidoreductase) has been
      purified from tetraether lipid membranes of the thermoacidophilic archaeon,
      Sulfolobus sp. strain 7. It consists of four different subunits with apparent
      molecular masses of 66, 37, 33, and 12 kDa on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The 66-kDa subunit contains a covalently
      bound flavin, the 37-kDa subunit is a possible iron-sulfur protein carrying three
      distinct types of EPR-visible FeS cluster, and the 33- and 12-kDa subunits are
      putative membrane-anchor subunits, respectively. While no heme group is detected
      in the purified complex II, it catalyzes succinate-dependent reduction of
      ubiquinone-1 and 2,6-dichlorophenolindophenol in the absence of phenazine
      methosulfate. The respiratory complex II of Sulfolobus sp. strain 7 appears to be
      novel in that it functions as a true succinate:caldariellaquinone oxidoreductase,
      although inherently lacking any heme group. This further indicates that the heme
      group of several respiratory complexes II may not be involved in the redox
      intermediates of the electron transfer from succinate to quinone.

PMID- 8537345
TI  - Nuclear magnetic resonance evidence for Ca(2+)-induced extrusion of the myristoyl
      group of recoverin.
AB  - Recoverin, a recently discovered member of the EF-hand protein superfamily,
      serves as a Ca2+ sensor in vision. A myristoyl or related N-acyl group covalently
      attached to the amino terminus of recoverin enables it to translocate to retinal
      disc membranes when the Ca2+ level is elevated. Two-dimensional 1H-13C shift
      correlation NMR spectra of recoverin containing a 13C-labeled myristoyl group
      were obtained to selectively probe the effect of Ca2+ on the environment of the
      attached myristoyl group. In the Ca(2+)-free state, each pair of methylene
      protons bonded to carbon atoms 2, 3, 11, and 12 of the myristoyl group gives rise
      to two peaks. The splittings, caused by nonequivalent methylene proton chemical
      shifts, indicate that the myristoyl group interacts intimately with the protein
      in the Ca(2+)-free state. By contrast, only one peak is seen for each pair of
      methylene protons in the Ca(2+)-bound state, indicating that the myristoyl group
      is located in an isotropic environment in this form. Furthermore, the 1H-13C
      shift correlation NMR spectrum of Ca(2+)-bound recoverin is very similar to that
      of myristic acid in solution. 1H-(13)C shift correlation NMR experiments were
      also performed with 13C-labeled recoverin to selectively probe the resonances of
      methyl groups in the hydrophobic core of the protein. The spectrum of Ca(2+)
      bound myristoylated recoverin is different from that of Ca(2+)-free myristoylated
      recoverin but similar to that of Ca(2+)-bound unmyristoylated recoverin. Hence,
      the myristoyl group interacts little with the hydrophobic core of myristoylated
      recoverin in the Ca(2+)-bound state. Three-dimensional (13C/F1)-edited (13C/F3)
      filtered heteronuclear multiple quantum correlation-nuclear Overhauser effect
      spectroscopy spectra of recoverin containing a 13C-labeled myristoyl group were
      obtained to selectively probe protein residues located within 5 A of the
      myristoyl group. The myristoyl group makes close contact with a number of
      aromatic residues in Ca(2+)-free recoverin, whereas the myristoyl group makes no
      observable contacts with the protein in the Ca(2+)-bound state. These NMR data
      demonstrate that the binding of Ca2+ to recoverin induces the extrusion of its
      myristoyl group into the solvent, which would enable it to interact with a lipid
      bilayer or a hydrophobic site of a target protein.

PMID- 8537346
TI  - Identification of Epstein-Barr virus nuclear antigen 1 protein domains that
      direct interactions at a distance between DNA-bound proteins.
AB  - The EBNA1 protein of Epstein-Barr virus (EBV) binds to and activates DNA
      replication from the EBV latent origin of replication, oriP, via a direct
      interaction with the two noncontiguous subelements of oriP. The EBNA1 molecules
      bound to the oriP subelements interact efficiently with each other by a DNA
      looping mechanism. We have previously mapped a region of EBNA1 (termed the
      looping region) that is required to mediate the interaction of the EBNA1
      molecules bound to the oriP subelements. We now demonstrate that two fragments of
      this region of EBNA1, which consist largely of an eight amino acid repeat, can
      mediate homotypic interactions when transferred to another DNA-binding protein.
      Protein interactions mediated by the EBNA1 looping region appear to be dependent
      on DNA binding since these interactions were detected between DNA-bound forms of
      the proteins only.

PMID- 8537347
TI  - p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after
      integrin cross-linking.
AB  - p120GAP forms distinct complexes with two phosphoproteins, p62 and p190. Here we
      have cloned a cDNA encoding a protein with 51% amino acid identity to p190
      (hereafter designated p190-A) and have designated it p190-B. The N-terminal
      portion of p190-B contained several motifs characteristic of a GTPase domain,
      while its C terminus contained a Rho GAP domain. A recombinant Rho GAP domain
      polypeptide showed GAP activity for RhoA, Rac1, and G25K/CDC42Hs.
      Immunoprecipitation and immunofluorescence studies demonstrated that p190-B
      protein was expressed in a variety of cells and was localized diffusely in the
      cytoplasm and in fibrillar patterns that co-localized with the alpha 5 beta 1
      integrin receptor for fibronectin. Adhesion of fibronectin-coated latex beads to
      cells resulted in recruitment of significant amounts of p190-B and Rho to the
      plasma membrane beneath the site of bead binding. In contrast, beads coated with
      polylysine or concanavalin A were unable to recruit p190-B or Rho. Additionally,
      anti-beta 1 or anti-alpha 5 integrin antibody-coated beads were also able to
      recruit large amounts of p190-B and Rho. These results identify a novel second
      member of the p190 family and establish the existence of a novel transmembrane
      link between integrins and a new protein p190-B and Rho.

PMID- 8537348
TI  - The central aromatic residue in loop L2 of RecA interacts with DNA. Quenching of
      the fluorescence of a tryptophan reporter inserted in L2 upon binding to DNA.
AB  - To determine the role of the central aromatic residue in one of the DNA binding
      domains in Escherichia coli RecA protein, we have constructed a protein in which
      a tryptophan fluorescence reporter is inserted in the place of phenylalanine
      residue 203 in loop L2, a putative DNA binding site, and measured its
      fluorescence. The modified protein is active both in vivo and in vitro. The
      binding of nucleotide cofactor (ATP or its analog adenosine 5'-O-3
      thiotriphosphate) does not modify the fluorescence. By contrast, the binding of
      DNA, both in the absence and presence of cofactor, strongly decreases the
      fluorescence in intensity (40-65%) and shifts the emission peak from 344 to 337
      nm. The change occurs both with single- and double-stranded DNA and also upon the
      binding of a second single-stranded DNA. The results indicate that the residue
      203 is in fact close to the first and second DNA binding sites. However, the
      quenching is not total and depends only slightly on the nature of DNA bases, thus
      suggesting an indirect interaction with DNA bases.

PMID- 8537349
TI  - Structure of the m4 cholinergic muscarinic receptor gene and its promoter.
AB  - Cholinergic muscarinic receptor genes are members of the G-protein receptor gene
      superfamily. In this study we describe the structure of the gene and promoter of
      the rat m4 muscarinic receptor gene. A rat cosmid clone containing the coding
      region for the m4 gene and 25 kilobases of upstream sequence was isolated. This
      clone directed expression of the rat m4 gene when introduced in IMR32 cells, a
      human neuroblastoma that expresses m4, but did not drive expression when
      introduced into Chinese hamster ovary cells, a line that does not express the m4
      gene. S1 nuclease, modified 5'-rapid amplification of cDNA ends and polymerase
      chain reaction analysis of rat cosmid DNA and cDNA showed that the gene consists
      of a 2.6-kilobase coding exon, extending 34 base pairs (bp) upstream from the
      initiating ATG, separated from a 460-493 bp noncoding exon by a 4.8-kilobase
      intron. DNA sequence analysis shows that the non-coding exon is GC-rich and that
      the promoter does not contain a TATA or CAAT box and has several consensus
      sequences for enhancer elements including five Sp-1 binding sites, one AP-2 site,
      one AP-3 binding site and two E-boxes within the proximal 600 bp. A reporter
      construct consisting of 1440 bp of flanking DNA and 80 bp of the first exon
      cloned into a luciferase reporter plasmid, drove cell specific expression in
      transient transfection assays. Removal of 1088 bp of the 5' end of this construct
      resulted in expression in non-m4 expressing cell lines suggesting there is a
      repressor element in this region.

PMID- 8537350
TI  - Mutations in the Escherichia coli Tus protein define a domain positioned close to
      the DNA in the Tus-Ter complex.
AB  - A new genetic screen for mutations in the tus gene of Escherichia coli has been
      devised that selects for Tus proteins with altered ability to arrest DNA
      replication. We report here the characterization of three such mutants: TusP42S,
      TusE49K, and TusH50Y. TusP42S and TusE49K arrest DNA replication in vivo at 36%
      of the efficiency of wild-type Tus, whereas TusH50Y functions at 78% efficiency.
      The loss of replication arrest activity did not correlate with changes in the
      stability of the Tus-TerB complexes formed by the mutant proteins. TusE49K formed
      a more stable protein-DNA complex than wild-type Tus (t1/2 of 178 versus 149 min,
      respectively) and TusP42 had a 9-min half-life, yet these two mutants showed
      identical efficiencies for replication arrest. When tested in vitro using a
      helicase assay or an oriC replication system, we observed a general, but
      imperfect, correlation between the in vivo and in vitro assays. Finally, the half
      lives of the mutant protein-DNA complexes suggested that the domain of Tus where
      these mutations are located is positioned close to the DNA in the Tus-Ter
      complex.

PMID- 8537351
TI  - A novel smooth muscle-specific enhancer regulates transcription of the smooth
      muscle myosin heavy chain gene in vascular smooth muscle cells.
AB  - Transient DNA transfection analysis of 5' end deletion mutants of the rabbit
      smooth muscle myosin heavy chain (SMHC) gene promoter was performed in primary
      cultures of rabbit vascular smooth muscle cells (VSMC). A positive element
      located at position -1,332 upstream of the transcription start site consistently
      gave the highest relative chloramphenicol acetyltransferase (CAT) activity (6.3
      +/- 1.5-fold over the minimal SMHC promoter), suggesting that inclusion of the
      extra 107-base pair (bp) DNA fragment between -1,332 and -1,225 could
      significantly enhance CAT activity in VSMC. Transfection of mutants into several
      muscle and nonmuscle cell lines did not show any significant CAT activity above
      control, showing that factors unique to smooth muscle cells were required for
      SMHC expression. Gel shift analysis indicated that multiple factors interacted
      with the 107-bp element, two of which appeared to show smooth muscle specificity.
      Tests of enhancer function in transfected VSMC indicated that the 107-bp fragment
      behaved as a classical enhancer, i.e. independently of position and orientation.
      These results indicate that a novel DNA element may regulate the tissue
      restricted expression of the SMHC gene and provides the first example of a role
      for a smooth muscle-specific enhancer in VSMC.

PMID- 8537352
TI  - Short isoform of POU factor Brn-3b can form a heterodimer with Brn-3a that is
      inactive for octamer motif binding.
AB  - The POU proteins Brn-3a and Brn-3b belong to a family of DNA binding
      transcription factors that share stretches of extensive homology. Both Brn-3a and
      Brn-3b are expressed as shorter and longer isoforms. The long form of Brn-3a is
      able to oncogenically transform primary fibroblasts. By contrast, the short form
      of Brn-3b (Brn-3b(s)) cannot transform fibroblasts but is able to specifically
      inhibit the transforming activity of Brn-3a(1). Moreover, Brn-3a(1) can act as a
      transcriptional transactivator, while Brn-3b(s) is not only unable to do so but
      in addition specifically inhibits the tranactivating activity of Brn-3a(1). Here,
      we show that the opposite and antagonistic activities of Brn-3a(1) and Brn-3b(s)
      proteins are due to their different DNA binding properties; Brn-3a(1) but not Brn
      3b(s) can form stable complexes with several octamer-related target DNA
      sequences. The presence of Brn-3b(s) completely inhibits the binding of Brn-3a(1)
      to DNA by preventing the formation of Brn-3a(1)-DNA complexes as well as by
      disrupting preformed complexes. Experiments with GST fusion proteins and in vitro
      binding studies suggest that the inhibition of Brn-3a(1) activity by Brn-3b(s)
      occurs via direct interaction of the two transcription factors in solution.
      Therefore, we hypothesize that Brn-3b(s) can act as a direct antagonist of Brn
      3a(1) by inhibiting its DNA binding through the formation of an inactive hetero
      oligomeric complex.

PMID- 8537353
TI  - Catenin-dependent and -independent functions of vascular endothelial cadherin.
AB  - Vascular endothelial cadherin (VE-cadherin, cadherin-5, or 7B4) is an endothelial
      specific cadherin that regulates cell to cell junction organization in this cell
      type. Cadherin linkage to intracellular catenins was found to be required for
      their adhesive properties and for localization at cell to cell junctions. We
      constructed a mutant form of VE-cadherin lacking the last 82 amino acids of the
      cytoplasmic domain. Surprisingly, despite any detectable association of this
      truncated VE-cadherin to catenin-cytoskeletal complex, the molecule was able to
      cluster at cell-cell contacts in a manner similar to wild type VE-cadherin.
      Truncated VE-cadherin was also able to promote calcium-dependent cell to cell
      aggregation and to partially inhibit cell detachment and migration from a
      confluent monolayer. In contrast, intercellular junction permeability to high
      molecular weight molecules was severely impaired by truncation of VE-cadherin
      cytoplasmic domain. These results suggest that the VE-cadherin extracellular
      domain is enough for early steps of cell adhesion and recognition. However,
      interaction of VE-cadherin with the cytoskeleton is necessary to provide strength
      and cohesion to the junction. The data also suggest that cadherin functional
      regulation might not be identical among the members of the family.

PMID- 8537354
TI  - A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity
      through its binding to an osteoblast-specific cis-acting element.
AB  - To identify osteoblast-specific cis-acting elements and trans-acting factors, we
      initiated an analysis of the promoter of a mouse osteocalcin gene, an osteoblast
      specific gene. In this promoter, we identified two osteoblast-specific cis-acting
      elements (Ducy, P. and Karsenty, G. (1995) Mol. Cell. Biol. 15, 1858-1869). The
      sequence of one of these elements, OSE2, is identical to the DNA-binding site of
      the PEBP2 alpha/AML-1 transcription factors, the mammalian homologues of the
      Drosophila Runt protein. Here we show, using nuclear extracts, recombinant
      protein, and a specific antiserum against AML-1 proteins in DNA-binding assays,
      that one member of this family, AML-1B, binds specifically to OSE2 and is
      immunologically related to OSF2, the factor present in osteoblast nuclear
      extracts that binds to OSE2. By DNA cotransfection experiments, we also
      demonstrate that AML-1B can increase the activity of a short osteocalcin promoter
      through its binding to OSE2. Lastly, the different mobilities of osteoblast
      nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes,
      along with the inability of OSF2 to be upregulated by retinoic acid, unlike the
      other PEBP2 alpha factors, suggest that OSF2 is a new member of this family of
      transcription factors. Thus, this study demonstrates that AML-1B can increase
      gene expression of an osteoblast-specific gene through its binding to an
      osteoblast-specific cis-acting element and presents evidence that OSF2 is a
      member of the PEBP2 alpha/AML-1 family of transcription factors.

PMID- 8537355
TI  - Regulation of vascular smooth muscle growth by alpha 1-adrenoreceptor subtypes in
      vitro and in situ.
AB  - Rat aorta smooth muscle cells which express all three alpha 1-adrenoreceptors
      (alpha 1A, alpha 1B and alpha 1D) were used to determine the effect of
      stimulation of alpha 1-adrenergic receptor subtypes on cell growth. "Combined"
      alpha 1-adrenoreceptor subtype stimulation with norepinephrine alone caused a
      concentration-dependent, prazosin-sensitive increase in protein content and
      synthesis: 48 h of stimulation at 1 microM increased cell protein to 216 +/- 40%
      of time-matched controls (p = 0.008) and RNA to 140 +/- 13% (p = 0.03); protein
      synthesis increased to 167 +/- 13% (p < 0.01) after 24 h. Stimulation with
      norepinephrine plus the selective alpha 1A/alpha 1D antagonist 5-methylurapidil
      produced greater increases in alpha-actin mRNA (270 +/- 40% at 8 h; p = 0.007),
      total cell protein (220 +/- 45% at 24 h; p = 0.004), and RNA (135 +/- 8% at 24 h;
      p = 0.01). These effects were prevented by pretreatment with the selective alpha
      1B antagonist chloroethylclonidine. Comparable results were obtained for intact
      aortae. Stimulation with norepinephrine plus 5-methylurapidil increased (p <
      0.05) tissue protein, RNA, dry weight, and alpha-actin mRNA; and as in culture
      cells, combined stimulation with norepinephrine alone attenuated these responses.
      By comparison, adventitia (fibroblasts) was unaffected. Removal of endothelial
      cells had no effect. alpha 1B mRNA decreased by 42 +/- 12% (p = 0.01) in cultured
      cells during combined alpha 1-adrenoreceptor stimulation and by 23 +/- 8% (p =
      0.03) for intact aorta. alpha 1D and beta-actin mRNA were unchanged in cultured
      cells, aorta media, and adventitia. These findings suggest that prolonged
      stimulation of chloroethylclonidine-sensitive, possibly alpha 1B-adrenoceptors
      induces hypertrophy of arterial smooth muscle cells and that stimulation of 5
      methylurapidil-sensitive, non-alpha 1B-adrenoreceptors attenuates this growth
      response.

PMID- 8537356
TI  - Identification of inhibitory and calmodulin-binding domains of the PDE1A1 and
      PDE1A2 calmodulin-stimulated cyclic nucleotide phosphodiesterases.
AB  - Using a bovine 61-kDa (PDE1A2) calmodulin-stimulated phosphodiesterase (CaM-PDE)
      cDNA and a bovine lung 59-kDa (PDE1A1) CaM-PDE cDNA reported here, we have
      identified two new regions within the primary structure of these two related
      isozymes that are important for regulation by Ca2+/CaM. PDE1A1 is identical to
      the PDE1A2 isozyme except for the amino-terminal 18 residues. In agreement with
      earlier studies, the CaM concentration required for half-maximal activation
      (KCaM) of recombinant PDE1A1 (0.3 nM) was approximately 10-fold less than the
      KCaM for recombinant PDE1A2 (4 nM). A series of deletion mutations of the PDE1A2
      cDNA removing nucleotide sequence encoding the first 46-106 aminoterminal
      residues were constructed and expressed using the baculovirus system. Deletion of
      the amino acids encompassing a previously identified, putative CaM-binding domain
      (residues 4-46) produced a polypeptide that was still activated 3-fold by CaM
      (KCaM approximately 3 nM). However, complete CaM-independent activation occurred
      when residues 4-98 were deleted. To determine the location of the additional CaM
      binding domain(s), the inhibitory potency of seven overlapping, synthetic
      peptides spanning amino acids 76-149 of PDE1A2 was tested using the CaM-activated
      enzyme. One peptide spanning amino acids 114-137 of PDE1A2 appeared to be the
      most potent inhibitor of CaM-stimulated activity. These results reveal the
      existence of a CaM-binding domain located approximately 90 residues carboxyl
      terminal to the putative CaM-binding domains previously identified within the
      PDE1A1 and PDE1A2 isozymes. Moreover, a discrete segment important for holding
      these CaM-PDEs in a less active state at low Ca2+ concentrations is located
      between the two CaM-binding domains.

PMID- 8537357
TI  - Purification and biochemical characterization of a mammalian phosphatidylinositol
      3,4,5-trisphosphate 5-phosphatase.
AB  - Characterization of the enzymes involved in metabolism of 3-phosphorylated
      inositol lipids and their subcellular localization revealed that in vitro a 5
      phosphatase activity was responsible for the degradation of phosphatidylinositol
      3,4,5-trisphosphate, whereas a 3-phosphatase activity hydrolyzed
      phosphatidylinositol 3-phosphate and/or phosphatidylinositol 3,4-bisphosphate.
      All these activities were localized in the cytosol. No phospholipase activities
      were detected. The cytosolic phosphatidylinositol 3,4,5-trisphosphate 5
      phosphatase activity was purified to near homogeneity using ion exchange,
      affinity, and size exclusion chromatography. Characterization of the purified
      phosphatase revealed that it is a magnesium-dependent 5-phosphatase that is able
      to hydrolyze phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5
      trisphosphate. The enzyme is only partially inhibited by neomycin and vanadate
      but is strongly inhibited by phosphatidylinositol 4,5-bisphosphate and to a
      slightly lesser extent by phosphatidylinositol 4-phosphate.

PMID- 8537358
TI  - Purification, characterization, and cDNA cloning of a 27-kDa lectin (L10) from
      horseshoe crab hemocytes.
AB  - We separated granular components of horseshoe crab hemocytes by a combination of
      centrifugation on sucrose density gradient and high performance liquid
      chromatography, and a 27-kDa protein termed L10 was found to be a major component
      in the large granules (Shigenaga, T., Takayenoki, Y., Kawasaki, S., Seki, N.,
      Muta, T., Toh, Y., Ito, A., and Iwanaga, S. (1993) J. Biochem. (Tokyo) 114, 307
      316). In the present work, lectin activity of this protein and its unique primary
      structure were elucidated. L10 was purified by four steps of chromatography,
      including dextran sulfate-Sepharose CL-6B, CM-Sepharose CL-6B, Sephacryl S-200,
      and Mono S. At least three 27-kDa isoproteins, named L10a, L10b, and L10c, were
      isolated. Their amino acid compositions were almost indistinguishable, and there
      were no amino sugars. All the isoforms had hemagglutinating activity against
      human A-type erythrocytes, in a Ca(2+)-independent manner with L10b showing the
      highest activity. The L10b-mediated hemagglutination was inhibited in the
      presence of N-acetylglucosamine or N-acetylallolactosamine, and the association
      constant (Ka) between L10b and N-acetylglucosamine was 1.95 x 10(4) M-1.
      Furthermore, L10b specifically agglutinated Staphylococcus saprophyticus KD.
      Ultracentrifugation analysis revealed that L10b is present in monomer form in
      solution. A cDNA coding for an isoform of L10 was isolated from a hemocyte cDNA
      library. The open reading frame of the 768-base pair cDNA coded for the signal
      sequence of 19 residues. The mature protein had 236 residues with the calculated
      molecular weight of 26,757. Amino acid sequences of the peptides derived from
      L10c exactly corresponded to the predicted sequence of the cDNA, whereas amino
      acid replacements of Ile-129 to Val and His-213 to Tyr existed both in L10a and
      L10b, suggesting that the cDNA codes for L10c. Cysteine was absent and there were
      five tandem repeats with 47 amino acids in each segment with internal sequence
      identities of 49-68%. The entire amino acid sequences had no significant sequence
      similarity with other known proteins.

PMID- 8537359
TI  - Cloning of an epithelial chloride channel from bovine trachea.
AB  - We have isolated and cloned a novel epithelial Cl- channel protein from a bovine
      tracheal cDNA expression library using an antibody probe. The antibody (alpha
      p38) was raised against a 38-kDa component of a homopolymeric protein that
      behaves as a Ca2+/calmodulin kinase II-, DIDS-, and dithiothreitol (DTT)
      sensitive, anion-selective channel when incorporated into planar lipid bilayers.
      The full-length cDNA is 3001 base pairs long and codes for a 903-amino acid
      protein. The clone does not show any significant homology to any other previously
      reported Cl- channel sequence. Northern analysis of bovine tracheal mRNA with a
      cDNA probe corresponding to the cloned sequence revealed a band at 3.1 kilobases,
      suggesting that close to the full-length sequence has been cloned. The full
      length open reading frame (2712 base pairs) has been expressed in Xenopus oocytes
      and in mammalian COS-7 cells. In oocytes, expression of the clone was associated
      with the appearance of a novel DIDS-, and DTT-sensitive, anion-selective
      conductance that was outwardly rectified and exhibited a reversal potential close
      to 0 mV. Whole-cell patch clamp studies in COS-7 cells transfected with the clone
      identified an ionomycin-, and DTT-sensitive chloride conductance that was not
      apparent in mock-transfected or control cells. In vitro translation studies have
      shown that the primary transcript codes for a protein migrating at 140 kDa under
      reduced conditions, significantly larger than the polypeptide recognized by alpha
      p38. We therefore suggest that either the 140-kDa translated product is a prepro
      form of the 38-kDa subunit of the previously identified bovine tracheal anion
      channel and that the primary transcript is post-translationally cleaved to yield
      the final product, or that the cloned channel and the previously identified
      bovine tracheal anion channel protein share an epitope that is recognized by the
      alpha p38 antibody.

PMID- 8537360
TI  - A unique dermatan sulfate-like glycosaminoglycan from ascidian. Its structure and
      the effect of its unusual sulfation pattern on anticoagulant activity.
AB  - A dermatan sulfate, similar to the mammalian glycosaminoglycans but not identical
      with any of them, has been isolated from the body of the ascidian Ascidia nigra.
      Degradation with chondroitin ABC lyase, analysis of the disaccharide products by
      digestion with chondro-4- and -6-sulfatases, and 1H and 13C NMR data confirm that
      the predominant structure is [4-alpha-L-IdoA-(2SO4)-1-->3-beta-D-GalNAc(6SO4)
      1]n. Mammalian dermatan sulfate is an anticoagulant due to its ability to
      potentiate inhibition of thrombin by heparin cofactor II. The structure in
      dermatan sulfate which binds to heparin cofactor II is [4-alpha-L-IdoA-(2SO4)-1-
      >3-beta-D-GalNAc(4SO4)-1]n, where n > or = 3. We have compared the ascidian
      dermatan sulfate with mammalian dermatan sulfate and with chemically oversulfated
      mammalian dermatan sulfate for anticoagulant activity as measured by the
      activated partial thromboplastin time assay and for its ability to potentiate
      heparin cofactor II. In spite of its high content of 2-O-sulfated alpha-L
      iduronic acid residues, the ascidian compound had no discernible anticoagulant
      activity and had low ability to potentiate heparin cofactor II. These results
      suggest that 4-O-sulfation of the N-acetyl-beta-D-galactosamine residues is
      essential for the anticoagulant activity of dermatan sulfate.

PMID- 8537361
TI  - Purification, cDNA cloning, and tissue distribution of bovine liver aldehyde
      oxidase.
AB  - Aldehyde oxidase was purified to homogeneity from bovine liver and primary
      structural information obtained by sequencing a series of cleavage peptides
      permitted the cloning of the corresponding cDNA. The cDNA is 4,630 base pairs
      long, and it consists of a 102-base pair 5'-untranslated region followed by a
      4017-base pair coding region and a 511-base pair 3'-untranslated region. The open
      reading frame predicts a 1339-amino acid polypeptide with a calculated molecular
      weight of 147,441, which is consistent with the size of the aldehyde oxidase
      monomeric subunit. The aldehyde oxidase polypeptide contains consensus sequences
      for iron-sulfur centers and a molybdopterin binding site. The amino acid sequence
      deduced from the cDNA shows significant similarity with that of xanthine
      dehydrogenases from various sources. The primary structure of bovine aldehyde
      oxidase is remarkably similar (approximately 86%) to that of the translation
      product of a cDNA recently isolated by Wright et al. (Wright, R. M., Vaitaitis,
      G. M., Wilson, C. M., Repine, T. B., Terada, L. S., and Repine, J. E. (1993)
      Proc. Natl. Acad. Sci. U.S.A. 90, 10690-10694) and reported to represent human
      xanthine dehydrogenase. With the help of a monospecific antibody raised against
      the purified protein and the isolated cDNA, the tissue distribution of the bovine
      aldehyde oxidase protein and corresponding mRNA was determined. Aldehyde oxidase
      is expressed at high levels in liver, lung, and spleen, and, at a much lower
      level, in many other organs.

PMID- 8537362
TI  - Effects of non-nucleoside inhibitors of human immunodeficiency virus type 1 in
      cell-free recombinant reverse transcriptase assays.
AB  - We have employed a cell-free human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) assay to study the effects of non-nucleoside inhibitors of RT
      (NNRTI) by directly monitoring specific HIV DNA products using a HIV-1 genome
      derived template and an oligodeoxynucleotide primer. As previously shown by
      ourselves and others, nucleoside analog triphosphates, e.g. 3'-azido-3'
      deoxythymidine triphosphate and 2',3'-dideoxyadenosine triphosphate, could
      directly inhibit HIV RT RNA-dependent DNA polymerase activity by causing chain
      termination, as visualized in a RT reaction that yields specific DNA products. In
      contrast, each of two NNRTIs, nevirapine and delavirdine, directly inhibited RT
      activity without causing chain termination effects. We also analyzed interactions
      between nucleoside analogs and NNRTIs or among NNRTIs by chain elongation/dNTP
      incorporation and/or steady-state kinetic assays. Combinations of nevirapine with
      the triphosphates of either the (-)-strand of 2',3'-dideoxy-3'-thiacytidine or
      2',3'-dideoxyadenosine yielded additive/synergistic effects on RT activity.
      However, only an additive effect was observed when combinations of nevirapine and
      3'-azido-3'-deoxythymidine triphosphate were employed. Combinations of nevirapine
      and delavirdine had an antagonistic effect on the inhibition of HIV-1 RT
      activity.

PMID- 8537363
TI  - The effect of carboxyl-terminal mutagenesis of Gt alpha on rhodopsin and guanine
      nucleotide binding.
AB  - The carboxyl terminus of G protein alpha subunits plays an important role in
      receptor recognition. To identify the amino acids that participate in this
      interaction, COOH-terminal mutants of alpha t (the transducin alpha subunit) were
      expressed in vitro and analyzed for their ability to interact with rhodopsin and
      to bind guanine nucleotide. Gly-348, the reported site of a beta turn, was
      replaced with other neutral amino acids without severely affecting rhodopsin
      binding. However, proline substitution abolished rhodopsin interaction,
      suggesting that flexibility is important at this site. A comparison between
      C347Y, which lost both rhodopsin and guanine nucleotide binding, and a mutant
      substituted with alpha q sequence (D346E/C347Y/G348N/F350V), in which guanine
      nucleotide binding was restored, implies that distinct motifs maintain the
      structure of the alpha subunit and are necessary for selective interaction with
      receptors. Surprisingly, mutants L344A, L349A, F350stop, and stop351A
      demonstrated a parallel loss of rhodopsin and guanine nucleotide binding. Altered
      profiles of L344A and F350stop on sucrose density gradients indicate that these
      mutants may undergo denaturation. The equivalent of alpha tL344A generated in
      alpha s and alpha i did not show such a severe loss of guanine nucleotide
      binding, revealing that the alpha t carboxyl terminus is unique in its
      susceptibility to changes in amino acid sequence.

PMID- 8537364
TI  - A unique thyroid hormone response element in the human immunodeficiency virus
      type 1 long terminal repeat that overlaps the Sp1 binding sites.
AB  - Long terminal repeat (LTR) of human immunodeficiency virus (HIV) type 1 is
      activated by thyroid hormone (T3) receptor alpha (T3R alpha) in the absence of
      ligand. Addition of T3 reverses this effect. This activity is mediated by a high
      affinity T3 response element (T3RE) within the HIV-1 LTR, termed the HIV-T3RE
      (bases -74 to -50), which coincides with the Sp1 element as demonstrated by
      mobility shift, DNaseI footprinting, and methylation interference analyses. HIV
      T3RE mediates ligand-independent activation of transcription by T3R alpha when
      linked to a heterologous promoter. In addition, the viral transactivator Tat
      synergizes with T3R alpha to activate the HIV-1 LTR in the absence of T3, which
      is relieved in its presence. These findings have implications for the possible
      control of HIV-1 LTR activity by T3.

PMID- 8537365
TI  - Rhodoquinone and complex II of the electron transport chain in anaerobically
      functioning eukaryotes.
AB  - Many anaerobically functioning eukaryotes have an anaerobic energy metabolism in
      which fumarate is reduced to succinate. This reduction of fumarate is the
      opposite reaction to succinate oxidation catalyzed by succinate-ubiquinone
      oxidoreductase, complex II of the aerobic respiratory chain. Prokaryotes are
      known to contain two distinct enzyme complexes and distinct quinones, menaquinone
      and ubiquinone (Q), for the reduction of fumarate and the oxidation of succinate,
      respectively. Parasitic helminths are also known to contain two different
      quinones, Q and rhodoquinone (RQ). This report demonstrates that RQ was present
      in all examined eukaryotes that reduce fumarate during anoxia, not only in
      parasitic helminths, but also in freshwater snails, mussels, lugworms, and
      oysters. It was shown that the measured RQ/Q ratio correlated with the importance
      of fumarate reduction in vivo. This is the first demonstration of the role of RQ
      in eukaryotes, other than parasitic helminths. Furthermore, throughout the
      development of the liver fluke Fasciola hepatica, a strong correlation was found
      between the quinone composition and the type of metabolism: the amount of Q was
      correlated with the use of the aerobic respiratory chain, and the amount of RQ
      with the use of fumarate reduction. It can be concluded that RQ is an essential
      component for fumarate reduction in eukaryotes, in contrast to prokaryotes, which
      use menaquinone in this process. Analyses of enzyme kinetics, as well as the
      known differences in primary structures of prokaryotic and eukaryotic complexes
      that reduce fumarate, support the idea that fumarate-reducing eukaryotes possess
      an enzyme complex for the reduction of fumarate, structurally related to the
      succinate dehydrogenase-type complex II, but with the functional characteristics
      of the prokaryotic fumarate reductases.

PMID- 8537366
TI  - Roles of amino acid residues surrounding phosphorylation site 1 of branched-chain
      alpha-ketoacid dehydrogenase (BCKDH) in catalysis and phosphorylation site
      recognition by BCKDH kinase.
AB  - Branched-chain alpha-ketoacid dehydrogenase is regulated by reversible
      phosphorylation of serine 293 (site 1) on the E1 alpha subunit. Alanine-scanning
      mutagenesis was used to examine the roles of residues surrounding serine 293 in
      catalysis by the dehydrogenase and in substrate recognition by branched-chain
      alpha-ketoacid dehydrogenase kinase. Alanine substitution of serine 293 resulted
      in a 10-fold increased Km for alpha-ketoisovalerate, a less increased (2.8-fold)
      Km for alpha-ketoisocaproate, but no change in Vmax or the Km for thiamine
      pyrophosphate. Alanine substitutions of arginine 288, histidine 292, and
      aspartate 296, residues highly conserved among alpha-ketoacid dehydrogenases,
      resulted in inactive enzymes. Each of the inactive E1 mutants bound to the E2
      core subunit with equal affinity as wild-type E1, and each produced circular
      dichroism spectra identical to that of wild-type E1. Two mutations, H292A and
      S293E, abolished the ability of E1 apoenzyme to reconstitute with thiamine
      pyrophosphate. Each alanine-substituted E1 was phosphorylated at site 1 by
      branched-chain alpha-ketoacid dehydrogenase kinase with similar rates, with the
      exception of the R288A mutant, which displayed no detectable phosphorylation.
      Thiamine pyrophosphate inhibited the phosphorylation of all mutant enzymes with
      the exception of H292A, the mutant E1 that did not bind thiamine pyrophosphate.

PMID- 8537367
TI  - Site-directed mutagenesis of evolutionary conserved carboxylic amino acids in the
      chitosanase from Streptomyces sp. N174 reveals two residues essential for
      catalysis.
AB  - The comparison of four sequences of prokaryotic chitosanases, belonging to the
      family 46 of glycosyl hydrolases, revealed a conserved N-terminal module of 50
      residues, including five invariant carboxylic residues. To verify if some of
      these residues are important for catalytic activity in the chitosanase from
      Streptomyces sp. N174, these 5 residues were replaced by site-directed
      mutagenesis. Substitutions of Glu-22 or Asp-40 with sterically conservative
      (E22Q, D40N) or functionally conservative (E22D, D40E) residues reduced
      drastically specific activity and kcat, while Km was only slightly changed. The
      other residues examined, Asp-6, Glu-36, and Asp-37, retained significant activity
      after mutation. Circular dichroism studies of the mutant chitosanases confirmed
      that the observed effects are not due to changes in secondary structure. These
      results suggested that Glu-22 and Asp-40 are directly involved in the catalytic
      center of the chitosanase and the other residues are not essential for catalytic
      activity.

PMID- 8537368
TI  - A clathrin-binding site in the hinge of the beta 2 chain of mammalian AP-2
      complexes.
AB  - The assembly of cytosolic clathrin into the cytoplasmic face of coated pits and
      coated vesicles appears to be driven by the clathrin-associated protein (AP)
      complexes. We have previously shown that one of the large chains of the AP
      complexes, the beta chain, is sufficient to drive coat assembly in vitro. This
      chain consists of two domains, the amino-terminal trunk and the carboxyl-terminal
      ear, linked by a "hinge." We report here that presence of the hinge in
      recombinant beta trunk or in recombinant beta ear fragments is essential for
      driving in vitro assembly of clathrin into coats. We have also used a binding
      assay to map the clathrin-binding site by nested deletion of hinge sequences to a
      50-residue region in the center of the hinge. This sequence is conserved in all
      known beta sequences from multicellular organisms. The interaction of a single
      beta hinge with a clathrin triskelion is weak, and we propose that recruitment of
      cytosolic clathrin to a forming coated pit involves simultaneous contacts between
      the legs of single clathrin trimers and the beta hinges of two or three membrane
      bound AP complexes. Uncoating is likely to require interruption of these
      contacts.

PMID- 8537369
TI  - Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase from papaver somniferum
      plant cell cultures. The enzyme catalyzing the formation of thebaine in morphine
      biosynthesis.
AB  - Acetyl coenzyme A:salutaridinol-7-O-acetyltransferase, a highly substrate
      specific enzyme, has been purified nearly 3,000-fold to homogeneity from Papaver
      somniferum plant cell suspension cultures. Purification was achieved by
      fractionated ammonium sulfate precipitation, dye-ligand affinity chromatography
      on matrex red A, gel filtration, ion exchange chromatography on Mono Q and a
      second dye-ligand affinity chromatography on fractogel TSK AF Blue. The purified
      enzyme was a single polypeptide with an M(r) = 50,000 displaying an isoelectric
      point of 4.8, a pH optimum between pH 6 and 9 and a temperature optimum at 47
      degrees C. The Km values for the substrate salutaridinol and the co-substrate
      acetyl co-enzyme A were 7 and 46 microM, respectively. Salutaridinol-7-O
      acetyltransferase catalyzes the stoichiometric transfer of the acetyl group from
      acetyl coenzyme A to the 7-OH group of salutaridinol yielding salutaridinol-7-O
      acetate, which is a new intermediate in morphine biosynthesis. Salutaridinol-7-O
      acetate undergoes a subsequent spontaneous allylic elimination at pH 8-9, leading
      to the formation of thebaine (1), the first morphinan alkaloid with the complete
      pentacyclic ring system, or at pH 7 leading to dibenz[d,f]azonine alkaloids that
      contain a nine-membered ring. Acetylation and subsequent allylic elimination is a
      new enzymic mechanism in alkaloid biosynthesis, which in the poppy plant can
      transform one precursor into alkaloids possessing markedly different ring
      systems, depending on the reaction pH.

PMID- 8537370
TI  - Mechanism of ribonuclease cytotoxicity.
AB  - Bovine seminal ribonuclease (BS-RNase), a dimeric homolog of bovine pancreatic
      ribonuclease A (RNase A), is toxic to mammalian cells. In contrast to dimeric BS
      RNase, a monomeric BS-RNase and RNase A are not cytotoxic and are bound tightly
      by cytosolic ribonuclease inhibitor. To elucidate the mechanism of ribonuclease
      cytotoxicity, we constructed a series of hybrid and semisynthetic enzymes and
      examined their properties. In five hybrid enzymes, divergent residues in BS-RNase
      were replaced with the analogous residues of RNase A so as to diminish an
      interaction with a putative cellular receptor. In a semisynthetic enzyme, the
      disulfide bonds that cross-link the monomeric subunits of dimeric BS-RNase were
      replaced with thioether bonds, which can withstand the reducing environment of
      the cytosol. Each hybrid and semisynthetic enzyme had ribonucleolytic and
      cytotoxic activities comparable with those of wild-type BS-RNase. These results
      suggest that dimeric BS-RNase (pI = 10.3) enters cells by adsorptive rather than
      receptor-mediated endocytosis and then evades cytosolic ribonuclease inhibitor so
      as to degrade cellular RNA. This mechanism accounts for the need for a cytosolic
      ribonuclease inhibitor and for the cytotoxicity of other homologs of RNase A.

PMID- 8537371
TI  - Strain-dependent occurrence of functional GTP:AMP phosphotransferase (AK3) in
      Saccharomyces cerevisiae.
AB  - The gene for yeast GTP:AMP phosphotransferase (PAK3) was found to encode a
      nonfunctional protein in 10 laboratory strains and one brewers' strain. The
      protein product showed high similarity to vertebrate AK3 and was located
      exclusively in the mitochondrial matrix. The deduced amino acid sequence revealed
      a protein that was shorter at the carboxyl terminus than all other known
      adenylate kinases. Introduction of a +1 frameshift into the 3'-terminal region of
      the gene extended homology of the deduced amino acid sequence to other members of
      the adenylate kinase family including vertebrate AK3. Frameshift mutations
      obtained after in vitro and in vivo mutagenesis were capable of complementing the
      adk1 temperature-conditional deficiency in Escherichia coli, indicating that the
      frameshift led to the expression of a protein that could phosphorylate AMP. Some
      yeasts, however, including strain D273-10B, two wine yeasts, and two more
      distantly related yeast genera, harbored an active allele, named AKY3, which
      contained a +1 frameshift close to the carboxyl terminus as compared with the
      laboratory strains. The encoded protein exhibited GTP:AMP and ITP:AMP
      phosphotransferase activities but did not accept ATP as phosphate donor. Although
      single copy in the haploid genome, disruption of the AKY3 allele displayed no
      phenotype, excluding the possibility that laboratory and brewers' strains had
      collected second site suppressors. It must be concluded that yeast mitochondria
      can completely dispense with GTP:AMP phosphotransferase activity.

PMID- 8537372
TI  - Proximity relationships between engineered cysteine residues in chicken skeletal
      myosin regulatory light chain. A resonance energy transfer study.
AB  - Resonance energy transfer was used to measure the distances between pairs of
      cysteines, Cys2 and Cys155 and Cys73 and Cys155, in recombinant chicken skeletal
      myosin regulatory light chains in the free and bound states. The fluorescent and
      nonfluorescent probes N-iodoacetyl-N'-(5-sulfo-1-naphthyl) ethylenediamine and N
      (4-dimethylamino-3,5-dinitrophenyl)maleimide were used as the donor and the
      acceptor, respectively. The distance between Cys2 and Cys155 was measured to be
      35 and 30 A in the absence and presence of myosin heavy chain, respectively,
      suggesting a slightly more compact structure for the light chain in the bound
      state. The distance between Cys73 and Cys155 measured in a similar manner was 31
      and 30 A in the free and bound states, respectively; this latter value is in good
      agreement with that derived from crystallographic structures. For heavy chain
      bound light chains, no measurable distance changes were detected with the binding
      of ATP or actin. These results show that no gross structural changes occur within
      the regulatory light chain during the contraction cycle, but that resonance
      energy transfer between other sites could be used to monitor potential changes in
      the myosin head upon the binding of nucleotides and actin.

PMID- 8537373
TI  - Binding affinities of tyrosine-phosphorylated peptides to the COOH-terminal SH2
      and NH2-terminal phosphotyrosine binding domains of Shc.
AB  - The adaptor protein Shc has been implicated in Ras signaling via association with
      many tyrosine-phosphorylated receptors, including growth factor receptors,
      antigen receptors on T and B cells, and cytokine receptors. Shc could interact
      with the activated receptors through the carboxyl-terminal Src homology 2 (SH2)
      domain or the structurally unrelated amino-terminal phosphotyrosine binding (PTB)
      domain. Using NMR and surface plasmon resonance techniques, we have measured the
      binding affinities of the SH2 and the PTB domains of Shc to a series of
      phosphotyrosine-containing peptides derived from known Shc binding sites.
      Tyrosine-phosphorylated peptides derived from Trk (pY490), polyoma virus middle T
      antigen (pY250), ErbB3 (pY1309), and epidermal growth factor receptor (pY1086,
      pY1148, and pY1114) that contain NPXpY sequences bind preferentially to the PTB
      domain of Shc with Kd values of 0.02-5.3 microM. The binding affinities of these
      peptides to the Shc SH2 domain were in the range of 220-1290 microM. In contrast,
      tyrosine-phosphorylated peptides from epidermal growth factor receptor (pY992,
      pY1173) and the zeta chain of the T-cell receptor bind preferentially to the SH2
      domain (Kd = 50-130 microM) versus the PTB domain (Kd > 680 microM). From these
      studies, the relative contribution of the individual domains of Shc for binding
      to the phosphotyrosine-containing portions of these proteins was determined. In
      addition, our data indicate that the high affinity binding of the PTB domain to
      the NPXpY-containing peptides results from a very high association rate and a
      rapid dissociation rate, which is similar to previous results observed for the
      SH2-phosphopeptide complexes.

PMID- 8537374
TI  - Kinetic and molecular differences in the amplified and non-amplified esterases
      from insecticide-resistant and susceptible Culex quinquefasciatus mosquitoes.
AB  - Two non-amplified esterases were purified from the insecticide-susceptible Pel SS
      strain of Culex quinquefasciatus. These were the two major esterase activity
      peaks in this strain. The two corresponding amplified carboxylesterases, Est
      alpha 2 and Est beta 2, involved in organophosphate sequestration were purified
      from two resistant C. quinquefasciatus strains. The Pel SS esterases were
      significantly less reactive with the organophosphates than those from the
      resistant strains. One of the Pel SS esterases was electrophoretically identical
      to amplified Culex Est beta 1. However, it differed kinetically, and in its
      nucleotide and predicted amino acid sequences from the two characterized
      amplified Est beta 1s, it is classified as Est beta 1(3). Restriction fragment
      analysis suggested Pel SS has only one Est alpha and one Est beta gene, while the
      resistant Pel RR has both amplified and non-amplified forms of Est alpha and Est
      beta. The EcoRI fragments for both Pel SS esterases were distinct from those of
      the amplified Est alpha 2(1), Est beta 2(1), or Est beta 1(1&2). An esterase with
      the same size EcoRI fragment as Est beta 1(3) was also present in Pel RR. This
      and restriction enzyme fragment analysis of C. quinquefasciatus field populations
      suggest that variability of the susceptible alleles may be lower than previously
      suggested. A non-amplified Est alpha with a unique EcoRI band was present in Pel
      RR. The previous esterase purification procedures may not have separated these
      amplified and non-amplified alleles. Hence, the small differences between the
      purified esterases from resistant strains may reflect mixtures of identical
      amplified alleles with different non-amplified alleles, which have significantly
      different k alpha values.

PMID- 8537375
TI  - An acute phase response factor/NF-kappa B site downstream of the junB gene that
      mediates responsiveness to interleukin-6 in a murine plasmacytoma.
AB  - The immediate early gene, junB, is induced by interleukin-6 (IL-6) in
      plasmacytomas. In order to identify enhancers that mediate this effect, we cloned
      upstream and downstream sequences flanking the gene into a luciferase reporter
      gene vector containing the junB promoter and evaluated the IL-6 inducibility of
      these sequences by transient expression in an IL-6-dependent plasmacytoma cell
      line. Although a 6.5-kilobase fragment of upstream flanking sequence did not
      increase the IL-6 inducibility of the junB promoter, a 222-base pair fragment was
      identified in 2.1 kilobases of down-stream flanking sequence that both up
      regulates the promoter and confers inducibility by IL-6. Point mutation of an
      acute phase response factor (APRF) site within this region significantly reduced
      up-regulation of the promoter in cells grown continuously in IL-6, as well as
      inducibility upon restimulation of cells with IL-6 after withdrawal from the
      growth factor. Point mutation of an NF-kappa B site sharing five nucleotides with
      the APRF site reduced up-regulation of the promoter but not inducibility by IL-6,
      whereas mutation of two other NF-kappa B sites in the 222-base pair fragment had
      no effect on expression. Western blotting of nuclear proteins purified by DNA
      affinity chromatography revealed inducible binding of Stat3 and constitutive
      binding of NF-kappa B p65 to the APRF/NF-kappa B site.

PMID- 8537376
TI  - Intermolecular phosphorylation between insulin holoreceptors does not stimulate
      substrate kinase activity.
AB  - We photocoupled benzoylphenylalanineB25, B29 epsilon-biotin insulin (BBpa
      insulin) to native insulin receptors to obtain a uniform receptor population with
      covalently bound, non-dissociable ligand. We employed BBpa-insulin-bound and
      autophosphorylated (activated) receptor to phosphorylate substrate insulin
      receptor under conditions where the substrate receptor never interacts with
      insulin. The substrate receptor becomes phosphorylated in this inter-receptor
      fashion and reaches a phosphorylation state 50% of the maximal obtainable by
      autophosphorylation. However, this phosphorylation does not activate the
      substrate receptor to any measurable degree. We conclude that intermolecular
      phosphorylation of the insulin holoreceptors is unlikely to be of physiological
      significance.

PMID- 8537377
TI  - Interaction of d-tubocurarine analogs with the Torpedo nicotinic acetylcholine
      receptor. Methylation and stereoisomerization affect site-selective competitive
      binding and binding to the noncompetitive site.
AB  - Analogs of d-tubocurarine were used to determine the individual effects of
      methylation, stereoisomerization, and halogenation of d-tubocurarine on the
      affinity for each of the two acetylcholine (ACh) binding sites of the Torpedo
      nicotinic acetylcholine receptor (AChR) and for the noncompetitive antagonist
      site. Eight analogs were synthesized, including three new compounds: 7'-O-methyl
      chondocurarine, 12'-O-methyl-chondocurarine, and 13'-bromo-d-tubocurarine. The
      two ACh sites differ in their affinities for d-tubocurarine by 400-fold, as shown
      by inhibition of [3H]ACh binding, whereas the affinity ratio for metocurine, the
      trimethylated derivative of d-tubocurarine, is reduced to 30 due to a decreased
      affinity for the high affinity site. Binding analysis of five d-tubocurarine
      analogs demonstrates that methylation of the phenols alone is responsible for the
      observed changes in affinity. Substitution with bromine or iodine at the 13'
      position affected affinity at both sites with a net increase in site selectivity.
      Stereoisomers of d-tubocurare had decreased affinity for only the high affinity
      ACh site. Thus, the ring systems, including the 12'- and 13'-positions and the 1
      position stereocenter, appear to be important in discriminating between the two
      ACh binding sites. Desensitization of the AChR was measured by increased affinity
      for [3H]phencyclidine. Binding to only the single, high affinity acetylcholine
      binding site, comprised by the alpha gamma-subunits, was required for partial
      desensitization of the AChR by d-tubocurarine and its analogs. Stronger
      desensitization, to the same extent observed in the presence of the agonist
      carbamylcholine, occurred upon binding by iodonated or brominated d-tubocurarine.
      Interaction of the analogs at the noncompetitive antagonist site of the AChR was
      also measured by [3H]phencyclidine binding. The bis-tertiary ammonium analogs of
      either the d- or l-stereoisomers bound to the noncompetitive antagonist binding
      site of the AChR with 100-fold higher affinity than the corresponding quaternary
      ammonium analogs.

PMID- 8537378
TI  - Enhanced association of platelet-activating factor acetylhydrolase with
      lipoprotein (a) in comparison with low density lipoprotein.
AB  - Paired samples of human Lipoprotein (a) (Lp(a)) and low density lipoprotein (LDL)
      were assayed for their platelet-activating factor (PAF) acetylhydrolase activity.
      Lp(a) displayed markedly enhanced PAF acetylhydrolase activity (approximately 7
      fold based on equal particle concentrations) in comparison to LDL isolated from
      the same individual. Lp(a)-associated acetylhydrolase exhibited properties
      observed for LDL-associated acetylhydrolase as well as for the purified enzyme;
      significant inhibition was obtained by treatment with diisopropylfluorophosphate
      (1 mM, 90%) and phenylmethanesulfonyl fluoride (5 mM, 50%). Furthermore, the
      hydrolytic activity of both lipoproteins was abolished with paraoxon (6 mM, IC50
      0.9 mM) and with the fluorescent and active site-directed probe 4-hexyl-(6'-O
      butyl-(4'-pyrenyl))-benzoic estersulfonyl fluoride (2) (KI(inact) = 525 microM),
      a novel irreversible inhibitor of PAF acetylhydrolase. Treatment with 2 and
      subsequent quantitation of protein-bound fluorescence suggests an increased
      concentration of enzyme associated to Lp(a) rather than alterations of kinetic
      constants due to the additional apolipoprotein apolipoprotein (a). Exposure of
      Lp(a) to Cu2+ (20 microM, 37 degrees C) was followed by a concomitant decrease of
      hydrolytic activity. A reduction of the basal activity by 91% was found after 15
      h. Whereas immunoprecipitation with anti-apoB antiserum could remove enzymatic
      activity of Lp(a) regardless of a reductive treatment with dithiothreitol,
      precipitation with anti-apolipoprotein (a)-antibodies was accompanied by a minor
      reduction (approximately 30%) of the PAF-hydrolyzing ability. These results
      suggest that PAF acetylhydrolase exhibits an enhanced association with Lp(a) due
      to an increased affinity to Lp(a) apolipoprotein B.

PMID- 8537379
TI  - Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type
      2A, associates with connectin through IS2, a p94-specific sequence.
AB  - p94, a muscle-specific member of calpain family, is unique in that it undergoes
      rapid and exhaustive autolysis with a half-life of less than 1 h resulting in its
      disappearance from muscle. Recently, p94 was shown to be responsible for limb
      girdle muscular dystrophy type 2A. To elucidate the muscular proteolytic system
      mediated by p94 and to solve the mystery of its unusually rapid autolysis, we
      searched for p94-binding proteins by the two-hybrid system. Although calpain
      small subunit plays a crucial role for regulation of ubiquitous calpains, it did
      not associate with p94. After a screening of skeletal muscle library, connectin
      (or titin), a gigantic filamentous protein spanning the M- to Z-lines of muscle
      sarcomere, was found to bind to p94 through a p94-specific region, IS2. The
      connectin-insoluble fraction of washed myofibrils contained full-length intact
      p94, suggesting that connectin regulates p94 activity.

PMID- 8537380
TI  - Analysis of mechanisms that determine dominant negative estrogen receptor
      effectiveness.
AB  - To analyze the mechanisms by which estrogen receptor (ER) activity is suppressed
      by dominant negative mutants, we examined the role of specific ER functions and
      domains in transcriptional repression. We previously described three
      transcriptionally inactive human ER mutants (the frameshift mutant S554fs, the
      point mutant L540Q, and the truncated receptor ER1-530), which act as effective
      dominant negative mutants, inhibiting the activity of wild type ER when they are
      coexpressed in mammalian cells. After additional mutational modifications, the
      ability of the ER mutants to suppress the activity of wild type ER was analyzed
      in cotransfection assays of the dominant negative mutants and wild type ER and an
      estrogen-responsive reporter gene (2ERE-TATA-CAT or 2ERE-pS2-CAT). Eliminating
      the ability of the three dominant negative mutants to bind to estrogen response
      element (ERE) DNA (by introducing three point mutations in their DNA binding
      domains) dramatically reduced, but did not completely abolish, the dominant
      negative activity of the ER mutants. The mutation G521R, which rendered the three
      mutants incapable of binding estradiol, also reduced, but did not abolish, their
      dominant negative activity. Immunoprecipitation with monoclonal or flag
      antibodies followed by Western blotting demonstrated that each of the original
      dominant negative ER mutants formed heterodimers with wild type ER. Rendering the
      dominant negative mutants dimerization deficient by the mutation L507R strongly
      reduced, but did not eliminate, their dominant negative activity. Deletion of the
      N-terminal A/B domain resulted in the nearly complete loss of inhibitory activity
      of the three dominant negative mutants. However, these double mutants retained
      their ability to heterodimerize with wild type ER, suggesting that dominant
      negative interference also occurs at an additional step beyond dimerization. Our
      data indicate that competition for ERE binding, formation of inactive
      heterodimers, and specific transcriptional silencing can all contribute to the
      dominant negative phenotype and that these receptors suppress the activity of
      wild type ER by acting at multiple steps in the ER-response pathway.

PMID- 8537381
TI  - Cloning and functional expression of rat CLC-5, a chloride channel related to
      kidney disease.
AB  - We have cloned a novel member of the CLC chloride channel family from rat brain,
      rCLC-5. The cDNA predicts a 83-kDa protein belonging to the branch including CLC
      3 and CLC-4, with which it shares approximately 80% identity. Expression of rCLC
      5 in Xenopus oocytes elicits novel anion currents. They are strongly outwardly
      rectifying and have a conductivity sequence of NO3- > Cl- > Br- > I- >> glutamate
      . Although CLC-5 has consensus sites for phosphorylation by protein kinase A,
      raising the intracellular cAMP concentration had no effect on these currents.
      Currents were also unchanged when rCLC-5 was coexpressed with rCLC-3 and rCLC-4,
      either singly or in combination. rCLC-5 is expressed predominantly in kidney and
      also in brain, lung, and liver. Along the nephron, rCLC-5 message is detectable
      in all tubule segments investigated, but expression in the glomerulus and the S2
      segment of the proximal tubule is low.

PMID- 8537382
TI  - A novel homeobox protein which recognizes a TGT core and functionally interferes
      with a retinoid-responsive motif.
AB  - We describe here a novel homeobox gene, denoted TGIF (5"TG3' interacting factor),
      which belongs to an expanding TALE (three amino acid loop extension) superclass
      of atypical homeodomains. The TGIF homeodomain binds to a previously
      characterized retinoid X receptor (RXR) responsive element from the cellular
      retinol-binding protein II promoter (CRBPII-RXRE), which contains an unusual DNA
      target for a homeobox. The interactions of both the homeprotein TGIF and receptor
      RXR alpha with the CREBPII-RXRE DNA motif occur on overlapping areas and generate
      a mutually exclusive binding in vitro. Transient cellular transfections
      demonstrate that TGIF inhibits the 9-cis-retinoic acid-dependent RXR alpha
      transcription activation of the retinoic acid responsive element. TGIF
      transcripts were detected in a restricted number of tissues. The canonical
      binding site of TGIF is conserved and is an integral part of several responsive
      elements which are organized like the CRBPII-RXRE. Hence, a novel auxiliary
      factor to the steroid receptor superfamily may participate in the transmission of
      nuclear signals during development and in the adult, as illustrated by the down
      modulation of the RXR alpha activities.

PMID- 8537383
TI  - Hypoxia induces vascular endothelial growth factor in cultured human endothelial
      cells.
AB  - Smooth muscle cells, macrophages, glial cells, keratinocytes, and transformed
      cells have been established as synthesis sites for vascular endothelial growth
      factor (VEGF). The modulating effects of VEGF are essentially limited to
      endothelial cells (ECs), the only cell type consistently shown to express VEGF
      receptors. VEGF has thus been considered to act exclusively via a paracrine
      pathway. We sought to determine whether the role of human ECs might, under
      selected conditions, extend beyond that of a target to involve contingency
      synthesis of VEGF. In both unstimulated human umbilical vein ECs (HUVECs) and
      human derma-derived microvascular ECs (HMECs), Northern analysis detected no VEGF
      transcripts. Phorbol-12-myristate 13-acetate (10(-7) M) treatment, however,
      induced VEGF mRNA expression in both HUVECs and HMECs, peaking at 3 and 6 h,
      respectively, and returning to undetectable levels by 12 h. In vitro exposure of
      HUVECs to a hypoxic environment (pO2 = 35 mm of mercury) for 12, 24, and 48 h and
      exposure of HMECs for 6, 12, 24, and 48 h induced VEGF mRNA in a time-dependent
      fashion. Re-exposure to normoxia (pO2 = 150 mm of mercury) for 24 h after 24 h of
      hypoxia returned VEGF mRNA transcripts to undetectable levels in HUVECs. Cobalt
      chloride and nickel chloride treatment each induced VEGF mRNA in ECs.
      Cycloheximide treatment further augmented expression of VEGF mRNA induced by
      cobalt chloride, nickel chloride, and hypoxia in HUVECs. VEGF protein production
      in hypoxia HUVECs was demonstrated immunohistochemically. Conditioned media from
      hypoxic HUVECs caused a 2-fold increase in the incorporation of tritiated
      thymidine. Finally, immune precipitates of anti-KDR probed with anti-Tyr(P)
      antibodies demonstrated evidence of receptor autophosphorylation in hypoxic but
      not normoxic HUVECs. These findings thus establish the potential for an autocrine
      pathway that may augment and/or amplify the paracrine effects of VEGF in
      stimulating angiogenesis.

PMID- 8537384
TI  - Cloning of cockroach allergen, Bla g 4, identifies ligand binding proteins (or
      calycins) as a cause of IgE antibody responses.
AB  - An allergen cloned from a Blattella germanica (German cockroach) cDNA library,
      encoded a 182-amino acid protein of 20,904 Da. This protein, designated B.
      germanica allergen 4 (Bla g 4), was expressed as a glutathione S-transferase
      fusion protein in Escherichia coli and purified by affinity chromatography and
      high-performance liquid chromatography. The prevalence of serum IgE antibody to
      recombinant Bla g 4 in 73 cockroach allergic patients with asthma ranged from 40%
      (antigen binding radioimmunoassay) to 60% (plaque immunoassay). Cockroach
      allergic patients gave positive intradermal skin tests to recombinant Bla g 4 at
      concentrations of 10(-3)-10(-5) micrograms/ml, whereas non-allergic controls, or
      cockroach allergic patients with no detectable serum IgE antibody to Bla g 4,
      gave negative skin tests to 1 microgram/ml. Polymerase chain reaction and
      Southern analysis identified a 523-base pair DNA encoding Bla g 4 in both B.
      germanica and Periplaneta americana (American cockroach). However, Northern
      analysis showed that mRNA encoding Bla g 4 was transcribed in B. germanica but
      not in P. americana, suggesting that allergen expression was species specific.
      Sequence similarity searches showed that Bla g 4 was a ligand binding protein or
      calycin and unexpectedly revealed that this family contained several important
      allergens: beta-lactoglobulin, from cow milk, and rat and mouse urinary proteins.
      Although the overall sequence homology between these proteins was low
      (approximately 20%), macromolecular modeling techniques were used to generate two
      models of the tertiary structure of Bla g 4, based on comparisons with the x-ray
      crystal coordinates of bilin binding protein and rodent urinary proteins. The
      results show that members of the calycin protein family can cause IgE antibody
      responses by inhalation or ingestion and are associated with asthma and food
      hypersensitivity.

PMID- 8537385
TI  - The cytochrome subunit is necessary for covalent FAD attachment to the
      flavoprotein subunit of p-cresol methylhydroxylase.
AB  - When p-cresol methylhydroxylase (PCMH) is expressed in its natural host
      Pseudomonas putida, or when the genes of the alpha and beta subunits of the
      enzyme are expressed together in the heterologous host Escherichia coli, flavin
      adenine dinucleotide (FAD) is covalently attached to Tyr384 of the alpha subunit
      and the correct alpha 2 beta 2 form of the enzyme is assembled. The
      apoflavoprotein has been expressed in E. coli in the absence of the beta
      cytochrome c subunit and purified. While noncovalent FAD binding to
      apoflavoprotein in the absence of the cytochrome subunit could not be directly
      demonstrated, circumstantial evidence suggests that this indeed occurs. Covalent
      flavinylation requires one molecule each of FAD and cytochrome for each
      flavoprotein subunit. The flavinylation process leads to the 2-electron-reduced
      form of covalently bound FAD, and the resulting alpha 2 beta 2 enzyme is
      identical to wild-type PCMH. This work presents clear evidence that covalent
      flavinylation occurs by a self-catalytic mechanism; an external enzyme or
      chaperon is not required, nor is prior chemical activation of FAD or of the
      protein. This work is the first to define the basic chemistry of covalent
      flavinylation of an enzyme to produce the normal, active species, and confirms a
      long standing, postulated chemical mechanism of this process. It also
      demonstrates, for the first time, the absolute requirement for a partner subunit
      in the post-translational modification of a protein. It is proposed that the
      covalent FAD bond to Tyr384 and the phenolic portion of this Tyr are part of the
      essential electron transfer path from FAD to heme.

PMID- 8537386
TI  - Topochemical catalysis achieved by structure-based ligand design.
AB  - Recently, a cyclic peptide ligand, cyclo-Ac-[CHPQG-PPC]-NH2, that binds to
      streptavidin with high affinity was discovered by screening phage libraries. From
      the streptavidin-bound crystal structures of cyclo-Ac-[CHPQGPPC]-NH2 and of a
      related but more weakly binding linear ligand, FSHPQNT, we designed linear thiol
      containing streptavidin binding ligands, FCH-PQNT-NH2 and Ac-CHPQNT-NH2, which
      are dimerized catalytically by the streptavidin crystal lattice of space group
      I222, as demonstrated by high performance liquid chromatography and mass
      spectrometry. The catalytic dimerization relies on presentation of the ligand
      thiols toward one another in the lattice. The streptavidin crystal lattice
      mediated catalysis achieved by structure-based design is the first example of
      catalysis of a chemical reaction by a protein crystal lattice. The spontaneous
      and crystal catalyzed rates of disulfide formation were determined by high
      performance liquid chromatography at pH 3.1, 4.0, 5.0, and 6.0. The ratio of the
      catalyzed to uncatalyzed rate was maximal at pH 3.1 (kcat/kuncat = 3.8),
      diminishing to 1.2 at pH 6.0. The crystal structures of the streptavidin-bound
      dimerized peptide ligands, FCHPQNT-NH2 dimer at 1.95 A and Ac-CHPQNT-NH2 dimer at
      1.80 A, are described and compared with the structures of streptavidin-bound
      FSHPQNT monomer and cyclo-Ac-[CHPQGPPC]-NH2 dimer.

PMID- 8537387
TI  - Possible v-Crk-induced transformation through activation of Src kinases.
AB  - p47gag-crk (v-Crk) encoded by avian sarcoma virus CT10, causes an elevation of
      tyrosine phosphorylation of several cellular proteins. The lack of a protein
      tyrosine kinase domain in v-Crk suggests its co-operation with cellular protein
      tyrosine kinase activity. We have shown that suppression of a certain fraction of
      c-Src activity by Csk may require the binding of Csk to tyrosine-phosphorylated
      paxillin. In this study, we detected co-immunoprecipitation of tyrosine
      phosphorylated paxillin with v-Crk in CT10-transformed chicken embryo fibroblasts
      (CEF), and demonstrated that v-Crk binding to paxillin can inhibit Csk binding to
      paxillin. A phosphotyrosine peptide, which can inhibit v-Crk binding to paxillin,
      did not inhibit Csk binding to paxillin, suggesting that v-Crk and Csk bind to
      different tyrosine-phosphorylated sites in paxillin. We also found that the
      kinase activity of the endogenous c-Src in CEF is elevated severalfold after CT10
      transformation. We therefore suggest that the competitive binding of
      overexpressed v-Crk affects an efficient interaction of Csk with tyrosine
      phosphorylated paxillin in CT10-transformed CEF. This would result in a failure
      in the suppression of the kinase activities of a population of c-Src and other
      Src family protein-tyrosine kinases as well, and these kinases may then
      contribute to the phosphorylation of cellular proteins in CT10-transformed CEF.

PMID- 8537389
TI  - A novel kinetic analysis to calculate nucleotide affinity of proofreading DNA
      polymerases. Application to phi 29 DNA polymerase fidelity mutants.
AB  - Amino acids Tyr254 and Tyr390 of phi 29 DNA polymerase belong to one of the most
      conserved regions in eukaryotic-type DNA polymerases. In this paper we report a
      mutational study of these two residues to address their role in nucleotide
      selection. This study was carried out by means of a new kinetic analysis that
      takes advantage of the competition between DNA polymerization and 3'-->5'
      exonuclease activity to measure the Km values for correct and incorrect
      nucleotides in steady-state conditions. This method is valid for any 3'-->5'
      exonuclease-containing DNA polymerase, without any restriction concerning
      catalytic rates of nucleotide incorporation. The results showed that the
      discrimination factor achieved by phi 29 DNA polymerase in the nucleotide binding
      step of DNA polymerization is 2.4 x 10(3), that is, a wrong nucleotide is bound
      with a 2.4 x 10(3)-fold lower affinity than the correct one. Mutants Y254F,
      Y390F, and Y390S showed discrimination values of 7.0 x 10(2), > 1.9 x 10(3), and
      2.9 x 10(2), respectively. The reduced accuracy of nucleotide binding produced by
      mutations Y254F and Y390S lead us to propose that phi 29 DNA polymerase residues
      Tyr254 and Tyr390, highly conserved in eukaryotic-type DNA polymerases, are
      involved in nucleotide binding selection, thus playing a crucial role in the
      fidelity of DNA replication. Comparison of the discrimination factors of mutants
      Y390S and Y390F strongly suggests that the phenyl ring of Tyr390 is directly
      involved in checking base-pairing correctness of the incoming nucleotide.

PMID- 8537388
TI  - Characterization of the complete genomic structure of the human WNT-5A gene,
      functional analysis of its promoter, chromosomal mapping, and expression in early
      human embryogenesis.
AB  - We report the complete genomic organization of the human WNT-5A gene, which
      encodes a cysteine-rich growth factor involved in cell-cell signaling during
      growth and differentiation. The gene comprises five exons with the terminal exon
      coding for a large 3'-untranslated region of approximately 6.5 kilobase pairs and
      utilizes multiple polyadenylation signals to generate at least four discrete
      transcripts. We discovered a new leader exon interrupted by a 411-base pair
      intron that was retained in our original cDNA cloning. The promoter region was
      located in a GpC-rich island and harbored numerous cis-acting elements including
      several GC boxes and Sp1, AP1, and AP2 binding motifs. It lacked TATA or CAAT
      boxes typical of housekeeping and growth factor genes. In support of this, primer
      extension revealed extension two transcription start sites. Transient cell
      transfection assays showed functional promoter activity for the 3.9-kilobase pair
      5'-flanking region. Interestingly, internal and 5' deletions revealed tha the
      distal promoter was not required for full transcriptional activity and that the
      first 631 base pairs of WNT-5A harbored the strongest promoter activity. Using a
      panel of rodent-human hybrid DNAs carrying portions of chromosome 3p, we mapped
      the gene to 3p14.2-p21.1, between a constitutional and a familial renal cell
      carcinoma-associated translocation. In situ hybridization analyses of early human
      embryos at 28-42 days of gestation revealed that WNT-5A transcripts were not
      restricted to the developing brain and limbs but were also observed in the
      mesenchyme bordering the pharyngeal clefts and pouches and in the developing
      gonads and kidneys. The relatively high expression in the celomic epithelium and
      in the precursors of follicles and seminiferous tubules suggest a novel role for
      WNT-5A in germ-cell differentiation. This study provides the molecular basis for
      discerning the regulation of the WNT-5A gene and offers the opportunity to
      investigate genetic disorders linked to this important gene.

PMID- 8537390
TI  - Regulation of NF-kappa B through the nuclear processing of p105 (NF-kappa B1) in
      Epstein-Barr virus-immortalized B cell lines.
AB  - Transcription factors of the NF-kappa B/Rel family are retained in the cytoplasm
      as inactive complexes through association with I kappa B inhibitory proteins.
      Several NF-kappa B activators induce the proteolysis of I kappa B proteins, which
      results in the nuclear translocation and DNA binding of NF-kappa B complexes.
      Here, we report a novel mechanism of NF-kappa B regulation mediated by p105 (NF
      kappa B1) precursor of p50 directly at the nuclear level. In Epstein-Barr virus
      immortalized B cells, p105 was found in the nucleus, where it was complexed with
      p65. In concomitance with NF-kappa B activation, mitomycin C induced the
      processing of p105 to p50 in the nucleus, while it did not affect the steady
      state protein levels of I kappa B alpha and p105 in the cytoplasm. Differently,
      phorbol 12-myristate 13-acetate induced a significant proteolysis of both I kappa
      B alpha and p105 in the cytoplasm, while it did not affect the protein level of
      p105 in the nucleus. These results suggest that in Epstein-Barr virus-positive B
      cell lines the nuclear processing of p105 can contribute to NF-kappa B activation
      in response to specific signaling molecules, such as DNA-damaging agents.

PMID- 8537391
TI  - Definition of a composite binding site for gp130 in human interleukin-6.
AB  - The helical cytokine interleukin-6 (IL-6) assembles a multiprotein receptor
      complex. The starting event in the activation of intracellular signaling is the
      binding of the IL-6/IL-6R alpha subcomplex to two gp130 chains. The
      homodimerization of gp130 is triggered by two distinct and independent regions of
      IL-6 called sites 2 and 3. Several IL-6 antagonists have been obtained that
      affect signaling, but not IL-6 IL-6R alpha subcomplex formation. In this paper,
      we analyze in detail the impact of these antagonists on gp130 binding and
      dimerization and show that each signaling variant affects gp130 dimerization in
      vitro and that biological activity on cells decreases in precise parallel to the
      decrease in gp130 dimerization in vitro. All IL-6 antagonists can be classified
      into two groups, mapping at either site 2 or 3 in correspondence to their mode of
      interaction with gp130. We found that site 3 is a large region, which includes
      residues at the beginning of helix D spatially flanked by residues in the
      putative AB loop and located at one extremity of the cytokine 4-helix bundle.
      Interestingly, in leukemia inhibitory factor, another cytokine that signals
      through gp130, site 3, is topologically conserved but has evolved to bind
      leukemia inhibitory factor receptor.

PMID- 8537392
TI  - Partial truncation of the yeast RNA polymerase II carboxyl-terminal domain
      preferentially reduces expression of glycolytic genes.
AB  - The largest subunit of RNA polymerase II contains an essential carboxyl-terminal
      domain (CTD) that consists of highly conserved heptapeptide repeats with the
      consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. Yeast cells with a partially
      truncated CTD grow slowly, are temperature- and cold-sensitive, and are unable to
      fully activate transcription of some genes. Screening a yeast wild-type cDNA
      library by means of comparative hybridization we find that CTD truncation
      preferentially reduces transcription of genes encoding glycolytic enzymes. Using
      a newly developed dual reporter assay we demonstrate that sensitivity to CTD
      truncation is conferred by the glycolytic gene promoters. Expression driven by
      glycolytic gene promoters is reduced, on average, about 3-fold in strains with
      the shortest CTD growing on either fermentable or nonfermentable carbon sources.
      Sensitivity to CTD truncation is particularly acute for the constitutively
      expressed ENO1 gene, which is reduced 10-fold in a strain with only eight CTD
      repeats. The sensitivity of constitutive ENO1 expression argues that CTD
      truncation can cause defects in uninduced as well as induced transcription.

PMID- 8537393
TI  - Molecular characterization of Golgin-245, a novel Golgi complex protein
      containing a granin signature.
AB  - The serum from a Sjogren's syndrome patient with anti-Golgi antibodies was used
      as a probe to isolate a 4.6-kilobase pair cDNA insert from a HeLa cDNA library.
      Expression of the cDNA in Escherichia coli and the in vitro translation products
      of the cDNA yielded a recombinant protein that migrated in SDS-polyacrylamide gel
      electrophoresis at 180 kDa. This protein was immuno-precipitated by the human
      anti-Golgi serum and by immune rabbit serum but not by normal human serum or
      preimmune rabbit serum. Western blot analysis showed that the prototype human and
      immune rabbit sera recognized a 245-kDa protein, suggesting that the isolated
      clone contained a partial cDNA. The 5'-upstream sequence obtained by the rapid
      amplification of cDNA ends methodology using human placental cDNA and the
      combined HeLa cDNA contained 6965 base pairs and combined HeLa cDNA contained
      6965 base pairs and encoded a protein of 245 kDa and, like other Golgi
      autoantigens described earlier, is highly rich in coiled-coils. The deduced amino
      acid sequence included the decapeptide ESLALEELEL, which was identified as one of
      two signature sequences previously reported in a family of peptide hormones and
      neuropeptides known as "granins". This is the first report of a Golgi complex
      autoantigen that bears structural similarities to the granin family of proteins.

PMID- 8537394
TI  - Altered expression of M beta 2, the class II beta-tubulin isotype, in a murine
      J774.2 cell line with a high level of taxol resistance.
AB  - A series of taxol- and taxotere-resistant J774.2 cell lines has been
      characterized with respect to altered expression of beta-tubulin, the cellular
      target for these drugs. Vertebrates have six classes of beta-tubulin isotypes,
      each displaying a distinct pattern of expression. Although the functional
      significance of multiple beta-tubulins has not been fully defined, there is
      evidence that the individual isotypes contribute to differences in microtubule
      dynamics and drug binding. To determine if alterations in the expression of beta
      tubulin isotypes play a role in taxol resistance, a PCR-based methodology was
      developed that permits highly specific amplification of each of the six known
      murine beta-tubulin isotypes. Two isotypes, M beta 5 and M beta 3, were expressed
      abundantly in the drug-sensitive parental J774.2 cells. Although expressed at an
      extremely low level in the parental cells, expression of the M beta 2 isotype was
      increased 21-fold (< 0.005) in the cell line most resistant to taxol. These
      findings suggest that a cell can alter its relative tubulin isotype composition
      in response to an external stress and specifically imply that altered expression
      of M beta 2, the class II beta-tubulin isotype, may contribute to the development
      of high resistance to taxol.

PMID- 8537395
TI  - Identification of a contractile-responsive element in the cardiac alpha-myosin
      heavy chain gene.
AB  - The mechanisms by which the cardiac-specific alpha-myosin heavy chain (alpha-MHC)
      gene responds to contractile activity was studied in cultured cardiomyocytes and
      in vivo. Deletion analysis of the alpha-MHC promoter transiently transfected into
      neonatal rat cardiomyocytes localized the contractile-responsive element within 
      80 to -40 base pairs of the transcriptional start site. Mutational analysis of an
      E-box motif at position -47 showed that it was necessary for the contractile
      response both in cultured cardiomyocytes and in the intact heart. Competition gel
      mobility shift experiments indicated that the protein-DNA complex formed within
      the -39 to -59 base pair region could be competed by the E-box element at -309 of
      the alpha-MHC gene and that base substitutions within an E-box motif at -47
      eliminated the protein-DNA complex. To identify the contractile-responsive
      nuclear protein, antibodies specific for E12/E47, an E-box binding basic-helix
      loop-helix (bHLH) protein, and antibodies recognizing upstream stimulatory factor
      (USF), a widely expressed bHLH-leucine zipper transcription factor, were studied
      for their ability to inhibit cardiomyocyte nuclear protein binding to the E-box
      motif at -47. Anti-USF antibody abolished formation of the protein-DNA complex,
      thus identifying the protein as antigenically related to USF and demonstrating
      that bHLH-leucine zipper proteins are involved in the contractile-induced
      expression of the cardiac alpha-MHC gene.

PMID- 8537396
TI  - Erythropoietin induces the tyrosine phosphorylation, nuclear translocation, and
      DNA binding of STAT1 and STAT5 in erythroid cells.
AB  - We have investigated whether Signal Transducing and Activators of Transcription
      (STAT) proteins become activated following the binding of erythropoietin (EPO) to
      immature erythroid cells from the spleens of mice infected with the anemia strain
      of Friend virus. STAT1 and STAT5 proteins are phosphorylated and translocated to
      the nucleus in EPO-treated cells. STAT1 and STAT5 DNA binding activities were
      also activated in an EPO-dependent manner. The presence of these STAT proteins in
      the DNA binding complex was confirmed by Western blot analysis of the proteins
      bound to the DNA element in the gel mobility shift assays. This EPO-dependent
      activation of STAT proteins was maximum within 10 min of exposure of the cells to
      10 units of EPO/ml, the concentration of EPO required for maximum STAT
      activation. The magnitude of the EPO-dependent STAT5 activation appeared to be
      greater than the EPO-dependent activation of STAT1. The significance of STAT
      protein activation in EPO signal transduction is discussed.

PMID- 8537397
TI  - CCAAT/enhancer-binding proteins alpha and beta interact with the silencer element
      in the promoter of glutathione S-transferase P gene during hepatocarcinogenesis.
AB  - We have previously identified a silencer in the glutathione S-transferase P (GST
      P) gene which is strongly and specifically expressed during chemical
      hepatocarcinogenesis. At least three trans-acting factors bind to multiple cis
      elements in the silencer. One of them, Silencer Factor-B (SF-B), is identical
      with CCAAT/enhancer-binding protein beta (C/EBP beta) and binds to GST-P Silencer
      1 (GPS1). Many C/EBP beta binding sites are recognized by each of the C/EBP
      isoforms. Western blot analyses of C/EBP isoforms during chemical
      hepatocarcinogenesis revealed a decrease of C/EBP alpha expression. However,
      there was no change in C/EBP beta level. In the nuclear extracts from normal
      liver, C/EBP alpha was the dominant form that bound to GPS1, whereas both C/EBP
      alpha and C/EBP beta bound to GPS1 in the nuclear extracts from carcinogenic
      liver. Furthermore, transfection assays showed that C/EBP alpha not only
      repressed the GST-P promoter activity but also attenuated the transcriptional
      stimulation by C/EBP beta. These observations strongly suggest that the ratio of
      C/EBP alpha to C/EBP beta is one of the important factors for the GST-P silencer
      activity, and the decrease of this ratio during hepatocarcinogenesis reduces the
      silencer activity and, consequently, increases the GST-P expression.

PMID- 8537398
TI  - Efficient association of an amino-terminally extended form of human latent
      transforming growth factor-beta binding protein with the extracellular matrix.
AB  - Latent transforming growth factor-beta (TGF-beta) binding protein-1 (LTBP-1) is a
      component of the high molecular weight latent TGF-beta complex found in various
      cells, including human platelets. LTBP-1 is observed as different molecular sizes
      in different cell types, probably due to proteolytic processing and alternative
      splicing. We here report a novel form of human LTBP-1, which is longer in its NH2
      terminal part (LTBP-1L). Northern hybridization analysis revealed that the LTBP
      1L is derived from a 7.0-kilobase mRNA, whereas the originally reported shorter
      form (LTBP-1S) is derived from a 5.2-kilobase mRNA. Transfection of cDNA for LTBP
      1L and -1S in COS cells revealed that LTBP-1L bound more efficiently to the
      extracellular matrix than did LTBP-1S. These results suggest that the different
      splice forms of LTBP-1 mediate different localization patterns of the latent TGF
      beta complexes in vivo.

PMID- 8537399
TI  - Mechanism for binding site diversity on ankyrin. Comparison of binding sites on
      ankyrin for neurofascin and the Cl-/HCO3- anion exchanger.
AB  - Ankyrins are a family of spectrin-binding proteins that associate with at least
      seven distinct membrane proteins, including ion transporters and cell adhesion
      molecules. The membrane-binding domain of ankyrin is comprised of a tandem array
      of 24 ANK repeats organized into four 6-repeat folding domains. Tandem arrays of
      ANK repeats have been proposed to mediate protein interactions in a variety of
      proteins including factors involved in the regulation of transcription and the
      cell cycle. This report provides several new insights into the versatility of ANK
      repeats of ankyrin in protein recognition, using neurofascin and the Cl-/HCO3-
      anion exchanger as model ligands and ankyrinR as the prototypic ankyrin.
      Different combinations of ANK repeat domains from this ankyrin form two distinct,
      high affinity binding sites for neurofascin. One site requires both repeat
      domains 3 and 4. The other site involves both repeat domains 2 and 3, although
      domain 2 has significant activity alone. The sites appear to be independent with
      Kd values of 3 and 14 nM, respectively. Both the Cl-/HCO3- anion exchanger and
      neurofascin can interact simultaneously with repeat domains 3 and 4, because
      neurofascin is unable to displace binding of the anion exchanger cytoplasmic
      domain to domains 3 and 4, despite having a 3-5-fold higher affinity. These
      results demonstrate two levels of diversity in the binding sites on ankyrin: one
      resulting from different combinations of ANK repeat domains and another from
      different determinants within the same combination of repeat domains. One
      consequence of this diversity is that ankyrin can accommodate two neurofascin
      molecules as well as the anion exchanger through interactions mediated by ANK
      repeats. The ability of ankyrin to simultaneously associate with multiple types
      of membrane proteins is an unanticipated finding with implications for the
      assembly of integral membrane proteins into specialized regions of the plasma
      membrane.

PMID- 8537400
TI  - Presence of N-unsubstituted glucosamine units in native heparan sulfate revealed
      by a monoclonal antibody.
AB  - Immunohistochemical application of antibodies against heparan sulfate
      proteoglycan core protein and heparitinase-digested heparan sulfate stubs showed
      the presence of heparan sulfate proteoglycan in all basement membranes of the rat
      kidney. However, a monoclonal antibody (JM-403) against native heparan sulfate
      (van den Born, J., van den Heuvel, L. P. W. J., Bakker, M. A. H., Veerkamp, J.
      H., Assmann, K. J. M., and Berden, J. H. M. (1992) Kidney Int. 41, 115-123)
      largely failed to stain tubular basement membranes, suggesting the presence of
      heparan sulfate chains lacking the specific JM-403 epitope. Heparan sulfate
      preparations from various sources differed markedly with regard to JM-403
      binding, as demonstrated by liquid phase inhibition in enzyme-linked
      immunosorbent assay, the interaction decreasing with increasing sulfate contents
      of the polysaccharide. Mapping of the JM-403 epitope indicated that it was
      dominated by one or more N-unsubstituted glucosamine unit(s), since treatments
      that destroyed or altered the structure of such units in heparan sulfate
      preparations (cleavage at N-unsubstituted glucosamine units with HNO2 at pH 3.9
      and N-acetylation with acetic anhydride, respectively), abolished antibody
      binding. Conversely, immunoreactivity could be induced in a (D-glucuronyl-1,4-N
      acetyl-D-glucosaminyl-1,4) polysaccharide by the generation of N-unsubstituted
      glucosamine N-unsubstituted glucosamine in a JM-403-binding heparan sulfate
      (preparation HS-II from human aorta) was demonstrated by an approximately 3-fold
      reduction in molecular size following HNO2 (pH 3.9) treatment. Further
      characterization of the epitope recognized by JM-403, based on enzyme-linked
      immunosorbent assay inhibition tests with chemically/enzymatically modified
      polysaccharides, indicated that one or more N-sulfated glucosamine units are
      invariable present, whereas L-iduronic acid and O-sulfate residues appear to
      inhibit JM-403 reactivity. It is concluded that the epitope contains one or more
      N-unsubstituted glucosamine and D-glucuronic acid units and is located in a
      region of the heparan sulfate chain composed of mixed N-sulfated and N-acetylated
      disaccharide units.

PMID- 8537401
TI  - Tissue-specific regulation of the type X collagen gene. Analyses by in vivo
      footprinting and transfection with a proximal promoter region.
AB  - During endochondral bone formation, hypertrophic chondrocytes initiate synthesis
      of type X collagen. Previous studies have shown that regulation of this molecule
      is at the level of transcription. To further explore this regulation, we have
      studied a segment of the type X collagen gene extending from 562 base pairs (bp)
      upstream to 86 bp downstream of the transcriptional start site. We have studied
      this "proximal promoter region" by both structural analysis by DNase I in vivo
      footprinting and functional analysis by transient transfections. In type X
      collagen-expressing, hypertrophic chondrocytes, in vivo footprinting detected a
      fully protected TATA region flanked by hypersensitive sites but no other major
      protection. Type X collagen-negative cells (nonhypertrophic chondrocytes and
      tendon fibroblasts) showed major protection at a number of other sites, most
      notably an 8-bp region overlapping an AP2 site and a 9-bp region including the
      sequence CACACA. The importance of the proximal promoter region in restricting
      expression of type X collagen to hypertrophic chondrocytes was supported by
      transfection studies. A chloramphenicol acetyltransferase construct containing
      this region directed 5-10-fold higher chloramphenicol acetyltransferase
      expression in hypertrophic chondrocytes than in the other cell types. A 2.6
      kilobase upstream fragment produced no additional effect. Thus, the proximal
      promoter region contains at least some regulatory elements for the cell-specific
      expression of type X collagen.

PMID- 8537402
TI  - Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6
      in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in
      MC3T3-E1 cells.
AB  - When a mouse osteoblastic cell line MC3T3-E1 was cultured in the presence of
      tumor necrosis factor alpha (TNF alpha), the release of prostaglandin E2 and the
      cyclooxygenase activity increased in a dose- and time-dependent manner. The
      increase of the enzyme activity was attributed mostly to the induction of
      cyclooxygenase-2 rather than cyclooxygenase-1 as judged by the inhibitory effect
      of NS398, Western blotting, and Northern blotting. In this system we attempted to
      elucidate the transcriptional regulation of the cyclooxygenase-2 gene. As
      examined by the luciferase assay, two positive regulatory regions (-186 to -131
      and -512 to -385 base pairs) were found in the 5'-flanking promoter region of the
      mouse cyclooxygenase-2 gene in the TNF alpha-stimulated cells. The former
      included putative NF-IL6 (C/EBP beta) and AP2 elements, and the latter contained
      the NF kappa B motif. A DNA probe including the NF-IL6 and AP2 sites gave
      positive bands upon electrophoretic mobility shift assay using the nuclear
      extracts of MC3T3-E1 cells. The bands were supershifted by the addition of anti
      NF-IL6 antibody but not by anti-AP2 antibody. A probe including the NF kappa B
      site also gave positive bands, which were supershifted by anti-NF kappa B p50 and
      p65 antibodies. Furthermore, when the motif of NF-IL6 or NF kappa B or both was
      subjected to point mutation, the luciferase activity was markedly reduced. These
      data suggested a potential role of both NF-IL6 and NF kappa B in the induction of
      cyclooxygenase-2 by TNF alpha.

PMID- 8537403
TI  - Identification and characterization of a novel family of serine/threonine kinases
      containing two N-terminal LIM motifs.
AB  - We previously isolated human cDNA coding for LIMK1 (LIM motif-containing protein
      kinase-1), a putative protein kinase containing two LIM motifs at the N terminus
      and an unusual protein kinase domain at the C terminus. In the present study, we
      isolated human cDNA encoding LIMK2, a second member of a LIMK family, with a
      domain structure similar to LIMK1 and 50% overall amino acid identity with LIMK1.
      The protein kinase domains of LIMK1 and LIMK2 are unique in that they contain an
      unusual sequence motif Asp-Leu-Asn-Ser-His-Asn in subdomain VIB and a highly
      basic insert between subdomains VII and VIII. Expression patterns of LIMK1 and
      LIMK2 mRNAs in human tissues differ significantly. Chromosomal localization of
      human LIMK1 and LIMK2 genes was assigned to 7q11.23 and 22q12, respectively, by
      fluorescence in situ hybridization. The Myc epitope-tagged LIMK1 and LIMK2
      proteins transiently expressed in COS cells exhibited serine/threonine-specific
      kinase activity toward myelin basic protein and histone in in vitro kinase assay.
      Immunofluorescence and subcellular fractionation analysis revealed that Myc
      tagged LIMK1 and LIMK2 were localized mainly in the cytoplasm. The "native" LIMK1
      protein endogenously expressed in A431 epidermoid carcinoma cells also exhibited
      serine/threonine kinase activity. The specific activity of native LIMK1 from A431
      cells was apparently much higher than that of "recombinant" LIMK1 ectopically
      expressed in COS cells, hence, it is likely that there is a mechanism, by which
      native LIMK1 is activated. A 140-kDa tyrosine-phosphorylated protein (pp140) was
      co-immunoprecipitated with native LIMK1 form A431 cell lysates; therefore, pp140
      may be a LIMK1-associated protein involved in the regulation of LIMK1 function.

PMID- 8537404
TI  - Identification and characterization of a novel protein kinase, TESK1,
      specifically expressed in testicular germ cells.
AB  - We have isolated cDNA clones encoding the rat and human forms of a novel protein
      kinase, termed TESK1 (testis-specific protein kinase 1). Sequence analysis
      indicates that rat TESK1 contains 628 amino acid residues, composed of an N
      terminal protein kinase consensus sequence followed by a C-terminal proline-rich
      region. Human TESK1 contains 626 amino acids, sharing 92% amino acid identity
      with its rat counterpart. The protein kinase domain of TESK1 is structurally
      similar to those of LIMK (LIM motif-containing protein kinase)-1 and LIMK2, with
      49-50% sequence identity. Phylogenetic analysis of the protein kinase domains
      revealed that TESK1 is most closely related to a LIMK subfamily. Chromosomal
      localization of human TESK1 gene was assigned to 9p13. Anti-TESK1 antibody raised
      against the C-terminal peptide of TESK1 recognized two polypeptides of 68 and 80
      kDa in cell lysates of COS cells transfected with human TESK1 cDNA expression
      plasmid. TESK1 protein expressed in COS cells exhibited serine/threonine kinase
      activity, when myelin basic protein was used as a substrate. Northern blot
      analysis revealed that TESK1 mRNA was specifically expressed in rat and mouse
      testicular germ cells. The TESK1 mRNA in the testis was detectable only after the
      18th day of postnatal development of mice and was mainly expressed in the round
      spermatids. These observations suggest that TESK1 has a specific function in
      spermatogenesis.

PMID- 8537405
TI  - Interaction of calreticulin with protein disulfide isomerase.
AB  - We report here that calreticulin interacts with protein disulfide isomerase
      (PDI). The PDI-calreticulin complex can be dissociated by Zn(2+)-iminodiacetate
      substituted Sepharose-agarose chromatography, suggesting that these interactions
      may be Zn2+-dependent. Direct interaction between calreticulin and PDI is also
      documented by calreticulin affinity chromatography. PDI was the only pancreatic
      microsomal protein retained on the calreticulum affinity column. Calreticulin and
      PDI were identified by their NH2-terminal amino acid sequence analysis,
      mobilities in SDS-polyacrylamide gel electrophoresis, binding of 45Ca2+, and
      their reactivity with specific antibodies. Using glutathione S-transferase
      calreticulin fusion proteins, we show that PDI interacts strongly with the P
      domain and only weakly with the N-domain of calreticulin. Expression of
      calreticulin domains and PDI as fusion proteins with GAL4 in the yeast two-hybrid
      system revealed that calreticulin interacted with PDI also under normal cellular
      conditions. Interaction with PDI required only the NH2-terminal region of the N
      domain (amino acid residues 1-83) and the P-domain (amino acid residues 150-240)
      of calreticulin. Importantly, interaction between calreticulin and PDI led to the
      modulation of their activities. In the presence of PDI, calreticulin does not
      bind Ca2+ with high affinity. Calreticulin or the N-domain of calreticulin
      inhibited PDI ability to refold scrambled RNase A.

PMID- 8537406
TI  - Cloning and expression of a cDNA encoding the beta-subunit (30-kDa subunit) of
      bovine brain platelet-activating factor acetylhydrolase.
AB  - Bovine brain platelet-activating factor (PAF) acetylhydrolase isoform Ib is a
      heterotrimeric enzyme. Its gamma-subunit (which, formerly, we called the 29-kDa
      subunit) acts as a catalytic subunit, whereas the alpha-subunit (45 kDa) is the
      bovine homolog of the product of human LIS-1, the causative gene of Miller-Dieker
      lissencephaly, indicating that this intracellular PAF acetylhydrolase plays a key
      role in brain development. In the current study, we cloned the cDNA for the beta
      subunit (30 kDa) of bovine brain PAF acetylhydrolase Ib. The predicted 229-amino
      acid sequence was homologous (63.2% identity) to that of the gamma-subunit,
      especially (86% identity) in the catalytic and PAF receptor homologous domains.
      The recombinant beta-protein produced in Escherichia coli showed significant PAF
      acetylhydrolase activity. A mutant protein, in which Ser48, which corresponds to
      the active serine residue of the gamma-subunit, was replaced with cysteine showed
      no enzymatic activity, suggesting Ser48 is the active serine residue. Although
      the beta- and gamma-subunits form a heterocomplex in the native enzyme, both
      recombinant beta- and gamma-proteins exist as a homodimer. The purified
      recombinant beta-protein was labeled readily with [1,3-H]diisopropyl
      fluorophosphate, whereas the beta-subunit in the native complex was only labeled
      with higher concentrations of [1,3-3H]diisopropyl fluorophosphate to a lesser
      extent than the gamma-subunit. Combined with our previous data, the present study
      demonstrated that bovine brain PAF acetylhydrolase Ib is a unique enzyme
      possessing two catalytic subunits and another, possibly regulatory, subunit.

PMID- 8537407
TI  - The basic helix-loop-helix/PAS factor Sim is associated with hsp90. Implications
      for regulation by interaction with partner factors.
AB  - Sim is a Drosophila developmental basic helix-loop-helix (bHLH) transcription
      factor containing a Per-Arnt-Sim (PAS) region of homology. Here we demonstrate
      that Sim, in analogy to the structurally related bHLH/PAS dioxin receptor, was
      stably associated with the molecular chaperone hsp90. In the case of the dioxin
      receptor, release of hsp90 and derepression of receptor function appear to be
      regulated by ligand binding and dimerization with Arnt, a non-hsp90-associated
      bHLH/PAS factor. Dimerization with Arnt very efficiently disrupted Sim-hsp90
      interaction, a process that required both the bHLH and PAS dimerization motifs of
      Arnt. Moreover, hsp90 was also released upon dimerization of Sim with the
      Drosophila PAS factor Per, whereas the hsp90-associated dioxin receptor failed to
      interact with Sim. These results indicate that hsp90 may play a role in
      conditional regulation of Sim function, and that Per and possibly bHLH/PAS
      partner factors may activate Sim by inducing release of hsp90 during the
      dimerization process.

PMID- 8537408
TI  - Keratinocyte transglutaminase promoter analysis. Identification of a functional
      response element.
AB  - Keratinocyte transglutaminase catalyzes isopeptide bond formation to yield the
      highly insoluble cross-linked envelope during terminal differentiation of
      epidermal cells. Transcriptional response elements were identified in the 5'
      flanking DNA of the gene for this enzyme by a combination of transient
      transfection and electrophoretic mobility shift analyses. Since human
      keratinocytes transcribed ineffectively transfected transglutaminase flanking
      DNA, a key feature of these experiments was the use of rat bladder epithelial
      cells as recipients. Serial deletion experiments identified by transient
      transfection an important response region containing three putative AP2-like
      response elements approximately 0.5 kilobases from the transcription initiation
      site. Oligonucleotides, each containing a single one of the elements, formed
      specific complexes with keratinocyte nuclear proteins. Two of the response
      elements were found to be functional by transfection in site-specific deletion
      experiments. Of these one formed specific DNA-protein complexes with nuclear
      proteins only from cells exhibiting keratinocyte differentiation. UV cross
      linking experiments estimated the protein component of the complex to be
      approximately 85 kDa. This response element alone increased substantially the
      transcription of a minimal transglutaminase promoter in transient transfections.
      Further characterization of the putative transcription factor binding to this
      response element may provide insight into the regulation of keratinocyte
      transglutaminase.

PMID- 8537409
TI  - In vitro assembly and disassembly of coatomer.
AB  - Coatomer, a complex of seven proteins, is the major component of the non-clathrin
      (COP I) membrane coat. We report here the first system to reversibly disassemble
      and reassemble this complex in vitro. Coatomer disassembles at high salt
      concentrations and reassembles when returned to a more physiological buffer.
      Using this system, we show that alpha-, beta'-, and epsilon-COP interact directly
      and that gamma-COP interacts with zeta-COP. A partial complex comprising alpha-,
      beta'-, and epsilon-COP, obtained after coatomer disassembly, can bind to
      membranes in vitro. This binding is, at least in part, mediated by interactions
      with cytoplasmic KKXX motifs of proteins normally retained in or retrieved to the
      endoplasmic reticulum. Using coatomer disassembly and epitope-specific
      antibodies, we also demonstrate that the N- and C-terminal domains of beta-COP
      are buried within the native coatomer complex. These results provide the first
      insights into how the coatomer is structured.

PMID- 8537410
TI  - Identification of the sites of interaction between lymphocyte phosphatase
      associated phosphoprotein (LPAP) and CD45.
AB  - Human lymphocyte phosphatase-associated phospho-protein (LPAP) is a
      phosphoprotein of unknown function that noncovalently associates with CD45 in
      lymphocytes. In CD45-deficient human T cells, LPAP protein is synthesized at
      normal levels but is more rapidly degraded than in wild-type cells. Expression of
      CD45 cDNA rescues LPAP protein expression. This strongly suggests that LPAP is
      protected from degradation through its interaction with CD45. We have mapped the
      sites of interaction between LPAP and CD45 employing chimeric CD45 molecules and
      LPAP deletion mutants. Our data demonstrate that the interaction between LPAP and
      CD45 is mediated via the transmembrane regions of both molecules. In addition,
      the intracytoplasmic amino acids adjacent to the transmembrane region of LPAP may
      influence its binding to CD45.

PMID- 8537411
TI  - Phosphorylation of threonine 558 in the carboxyl-terminal actin-binding domain of
      moesin by thrombin activation of human platelets.
AB  - The phosphorylation and localization of the membrane-linking protein moesin was
      analyzed during early activation of platelets with thrombin. Activated platelets
      elaborate filopodia and spread to assume flat pancake-like shapes, and moesin is
      localized in filopodia and cell body. In resting platelets, approximately 25% of
      moesin molecules are phosphorylated as shown by metabolic labeling with 32P(i)
      and by isoelectric focusing. Within seconds after exposure to thrombin,
      phosphorylation increases, reaching a maximum of 35% labeled molecules by 1 min,
      followed by a decrease to a new basal level within 5 min. This modification
      affects a single residue, Thr558, which is located within or close to a binding
      site for F-actin. Rapid shifts (0-100%) in the number of phosphorylated molecules
      are observed in the presence of inhibitors of serine/threonine kinases and
      phosphatases. Inhibitors affecting tyrosine phosphorylation also modulate
      phosphorylation at this site suggesting that the enzymes involved in the
      modification of Thr558 are regulated by tyrosine phosphorylation. Platelets
      respond to both extremes of modification by forming extremely long filopodia and
      the absence of spreading on glass. Completely phosphorylated moesin is
      concentrated together with F-actin in the center of the cell. The rapid
      modification of moesin at or near its actin-binding domain suggests a model for
      regulated membrane-cytoskeleton interaction during cell activation.

PMID- 8537412
TI  - Tetanus toxin inhibits neuroexocytosis even when its Zn(2+)-dependent protease
      activity is removed.
AB  - Tetanus toxin (TeTX) is a dichain protein that blocks neuroexocytosis, an action
      attributed previously to Zn(2+)-dependent proteolysis of synaptobrevin (Sbr) by
      its light chain (LC). Herein, its cleavage of Sbr in rat cerebrocortical
      synaptosomes was shown to be minimized by captopril, an inhibitor of certain
      metalloendoproteases, whereas this agent only marginally antagonized the
      inhibition of noradrenaline release, implicating a second action of the toxin.
      This hypothesis was proven by preparing three mutants (H233A, E234A, H237A) of
      the LC lacking the ability to cleave Sbr and reconstituting them with native
      heavy chain. The resultant dichains were found to block synaptosomal transmitter
      release, albeit with lower potency than that made from wild type LC; as expected,
      captopril attenuated only the inhibition caused by the protease-active wild type
      toxin. Moreover, these protease-inactive toxins or their LCs blocked evoked
      quantal release of transmitter when micro-injected inside Aplysia neurons. TeTX
      was known to stimulate in vitro a Ca(2+)-dependent transglutaminase (TGase)
      (Facchiano, F., and Luini, A. (1992) J. Biol. Chem. 267, 13267-13271), an affect
      found here to be reduced by an inhibitor of this enzyme, monodansylcadaverine.
      Accordingly, treatment of synaptosomes with the latter antagonized the inhibition
      of noradrenaline release by TeTX while not affecting Sbr cleavage. This drug also
      attenuated the inhibitory action of all the mutants. Hence, it is concluded that
      TeTX inhibits neurotransmitter release by proteolysis of Sbr and a protease
      independent activation of a neuronal TGase.

PMID- 8537413
TI  - Novel polyaminolipids enhance the cellular uptake of oligonucleotides.
AB  - Two new polyaminolipids have been synthesized for the purpose of improving
      cellular uptake of oligonucleotides. The amphipathic compounds are conjugates of
      spermidine or spermine linked through a carbamate bond to cholesterol. The
      polyaminolipids are relatively nontoxic to mammalian cells. In tissue culture
      assays, using fluorescent-tagged or radiolabeled triple helix-forming
      oligonucleotides, spermine-cholesterol and spermidine-cholesterol significantly
      enhance cellular uptake of the oligomers in the presence of serum. Spermine
      cholesterol is comparable with DOTMA/DOPE (a 1:1 (w/w) formulation of the
      cationic lipid N-[1-(2,3-dioleyloxy)-propyl]-N,N,N-trimethylammonium chloride
      (DOTMA) and the neutral lipid dioleylphosphatidylethanolamine (DOPE)) in
      increasing cellular uptake of oligonucleotides, while spermidine-cholesterol is
      more efficient. The internalized oligonucleotides are routed to the nucleus as
      early as 20 min after treatment, suggesting that the polyaminolipids increase the
      permeability of cellular membranes to oligonucleotides. At later times, much of
      the incoming oligonucleotides are sequestered within punctate cytoplasmic
      granules, presumably compartments of endosomal origin. Coadministration with
      polyaminolipids markedly improves the cellular stability of the oligonucleotides;
      more than 80% of the material can be recovered intact up to 24 h after addition
      to cells. In the absence of the polyaminolipids, nearly all of the material is
      degraded within 6 h. These data suggest that the new polyaminolipids may be
      useful for the delivery of nucleic acid-based therapeutics into cells.

PMID- 8537415
TI  - X-gene product antagonizes the p53-mediated inhibition of hepatitis B virus
      replication through regulation of the pregenomic/core promoter.
AB  - Employing the glutathione S-transferase column retention method and far Western
      analysis, we found a physical association between tumor suppressor p53 and the
      hepatitis B virus X-gene product, which led us to study the function of observed
      interaction in relation to viral propagation. In the cell culture-based in vitro
      replication system, expression of p53 resulted in dramatic inhibition of viral
      replication, and this inhibition was relieved by the coexpression of the X-gene
      product in a dose-dependent manner. Furthermore, the activity of pregenomic/core
      promoter, responsible for the synthesis of pregenomic RNA, was almost completely
      inhibited upon expression of p53, and as in the replication assay, the inhibition
      was rescued by the coexpression of the X-gene product in a dose-dependent manner.
      Based on these results, we propose that the ratio of X-gene product to p53 is an
      important factor determining the fate of viral replication through modulation of
      the pregenomic/core promoter.

PMID- 8537414
TI  - An interaction between the Escherichia coli RecF and RecR proteins dependent on
      ATP and double-stranded DNA.
AB  - The DNA binding and ATPase activities of RecF protein are modulated by RecR
      protein. Stoichiometric amounts of RecF protein bind to double-stranded (ds) DNA
      (about 1 RecF monomer/4-6 base pairs) in the presence of adenosine 5'-O-(3
      thio)triphosphate (ATP gamma S), forming a homogeneous protein coating on the
      DNA. Little or no cooperativity is evident in the binding process. In the
      presence of ATP, RecF binding to dsDNA is much weaker, and no RecF protein
      coating forms. Instead, small numbers of RecF protomers are interspersed randomly
      along the DNA. RecR protein does not bind appreciably to the dsDNA under these
      same conditions. However, a protein coating, similar to that which was observed
      with RecF protein alone in the presence of ATP gamma S, was produced when both
      RecF and RecR proteins were incubated with dsDNA in the presence of ATP. An
      interaction between RecF and RecR enables both proteins to bind tightly to the
      dsDNA in an approximately 1:1 molar ratio. We also report a weak ATP hydrolytic
      activity of RecF which is stimulated by RecR.

PMID- 8537416
TI  - Prospective, randomized study of the efficacy of pressure garment therapy in
      patients with burns.
AB  - A randomized, prospective study was undertaken to determine the efficacy of
      pressure garment therapy in patients with burns. Patients were randomly assigned
      to receive either pressure garment therapy or no pressure garment therapy.
      Patients were observed by use of the Vancouver Burn Scar Assessment Scale to
      assess the maturity of all involved areas. One hundred and twenty-two consecutive
      patients were enrolled in the study; 64 were assigned to pressure garment therapy
      and 58 to no pressure garment therapy. Eight of the patients receiving pressure
      garment therapy and nine receiving no pressure garment therapy were not involved
      in the follow-up. No significant differences were found between the two groups
      when age, body surface area burn, length of hospital stay, or time to wound
      maturation were compared.

PMID- 8537417
TI  - Use of a helium-oxygen mixture in the treatment of postextubation stridor in
      pediatric patients with burns.
AB  - A mixture of helium and oxygen is less dense than room air. This property allows
      the gas to flow with less turbulence past airway narrowings, thereby decreasing
      airway resistance and increasing the volume of gas exchange. Previous studies
      demonstrated that airway obstruction that is manifested by stridor was present in
      92% of patients requiring reintubation. Eight pediatric patients with burns in
      whom postextubation stridor or retractions unresponsive to racemic epinephrine
      developed, were treated with "heliox" (helium and oxygen) for 28 +/- 5 hours with
      an initial helium concentration between 50% and 70%. Of the eight patients
      treated with heliox, only two experienced respiratory distress and required
      reintubation. Both patients had stridor for a longer time before the initiation
      of heliox therapy compared with those patients who did not require reintubation.
      After initiation of heliox therapy, patients experienced a significant decrease
      in respiratory distress scores (6.8 +/- 0.7 vs 2.0 +/- 0.7). Heliox was able to
      relieve persistent stridor and thereby aid in the prevention of respiratory
      distress and reintubation.

PMID- 8537418
TI  - Serum copper and zinc concentrations in patients with burns in relation to burn
      surface area.
AB  - Serum zinc and copper concentrations were measured by flame atomic absorption
      spectroscopy in 34 patients between 1 and 3 weeks after thermal injury. Mean
      (range) admission burn surface area was 29.8% (10% to 79%), and mean (range)
      serum zinc and copper concentrations within the first postburn week were 0.59
      (0.2 to 1.5) and 0.74 (0.1 to 1.6) mg/L, respectively. Serum copper concentration
      was inversely correlated with burn surface area (r = -0.611, p < 0.01), whereas
      serum zinc concentration showed no such association. In the first postburn week
      hypocupremia (< 0.7 mg/L) was found in 15 of 32 (48%) of patients and
      hypozincemia (< 0.7 mg/L) in 21 of 32 (68%). Serum copper concentrations in
      patients with less than 15% burns remained within normal limits throughout the
      study period, but hypozincemia was found in patients irrespective of burn surface
      area. Long-term monitoring of two patients with 79% and 70% burns showed initial
      hypocupremia and hypozincemia. Hypocupremia only resolved in the patient with 79%
      burns when skin healing was almost complete 75 days after burns. Postburn
      hypozincemia was found to be very variable and not associated with either serum
      albumin concentration or periods of clinical sepsis. Because major burn injuries
      are associated with hypocupremia, serial monitoring is recommended with
      appropriate copper supplementation.

PMID- 8537419
TI  - The effect of smoke inhalation on bradykinin metabolism by the perfused and
      ventilated rat lung.
AB  - The effect of smoke inhalation on bradykinin metabolism was studied in the rat
      lung perfused with Ringer's bicarbonate solution. After smoke (from cotton,
      polyester, or seat cushion material) inhalation, tritium-labeled bradykinin was
      added to the Ringer's bicarbonate solution, and then the lung perfusion effluent
      aliquots containing bradykinin and its metabolic fragments were collected after a
      single transpulmonary passage. For the 20 control rats without smoke inhalation,
      91% of the bradykinin dose was metabolized, with Pro-Pro (I), 49%, and Arg-Pro
      Pro-Gly-Phe (II), 32%, being the predominant bradykinin cleavage fragments. For
      12 rats with smoke inhalation, 89% of the bradykinin dose was metabolized, with I
      (28%) and II (36%) being the major bradykinin cleavage fragments. The type of
      smoke did not significantly alter the capacity of the rat lung to metabolize
      bradykinin. Exposure to smoke from seat cushion material for more than 3 minutes
      caused pulmonary edema and thickening, and smoke exposure for more than 5 minutes
      caused loss of integrity at the lung alveolar-capillary interface. In contrast,
      exposure to cotton or polyester smoke did not cause any observable gross changes
      of the lung. Electron microscopic examination of lung exposed to seat cushion
      material smoke revealed considerable damage, with the type I epithelium existing
      as patches on the alveolar surface and capillary endothelium separated from the
      basement lamina. Thus in our model acute, short-term inhalation of smoke did not
      significantly alter the amount of bradykinin metabolized by the pulmonary
      endothelium so long as the integrity of the lung alveolar-capillary interface was
      maintained, although there seemed to be a moderate shift in the amount of major
      cleavage fragments from I to II.

PMID- 8537420
TI  - Cultured epithelial autografting on meshed skin graft scars: evaluation of skin
      elasticity.
AB  - Many patients with meshed skin graft scars complain of the scars' unsightly
      appearance and hardness. Since 1989 we have shaved away meshed skin graft scars
      and then resurfaced the area with autologous cultured epithelium in nine
      patients. This method improved the disfigurement of meshed skin graft scars, with
      minimal sacrifice of normal donor skin. Furthermore, autologous cultured
      epithelium grafted areas had high skin elasticity compared with meshed skin graft
      scars, as measured with a noninvasive suction device.

PMID- 8537421
TI  - Homodigital flaps--especially for treatment of the burned hand.
AB  - Burn deformities involving the hand can cause a devastating impairment that often
      requires ingenious solutions to improve function. Fortunately, a skin shortage
      usually can be expeditiously replaced by autogenous skin grafts; otherwise, a
      vascularized flap may be imperative. If that is so, use of a donor site from the
      digit itself would always be preferable, because normal sensation potentially
      could be maintained with similar thin, extensile, and durable tissue. The sides
      of the finger often have been protected from the thermal injury and are available
      for use as homodigital flaps. Although technically this form of homodigital flap
      is an axial flap because it incorporates dorsal digital artery branches, the
      proper digital artery is always spared. The immediate transfer of a homodigital
      flap completes the desired reconstruction in a single stage, which allows early
      initiation of hand mobilization and rehabilitation.

PMID- 8537422
TI  - Effect of penile burns on sexual function.
AB  - In this article the psychologic problems that occur after burns to the penis are
      investigated. The statistical power of this study is limited because of the small
      number of patients in this study. There seems to be a significant difference in
      the physical and emotional relationships of patients who required skin grafts to
      the penis compared with the relationships of patients with encephalopathy after
      their injury.

PMID- 8537423
TI  - Diminished adaptive behaviors among pediatric survivors of burns.
AB  - Life for pediatric survivors of burns appears difficult to most observers. In an
      assessment by use of the Child Behavior Checklist (CBCL), survivors' parents
      reported that approximately 30% of the children had significant problems. The
      Vineland Adaptive Behavior Scales were used to gather further information
      concerning the children's personal and social sufficiency and functioning. Thirty
      four pediatric burn survivors (28 boys and 6 girls, ages 9 to 19, 1 to 5 years
      after burn, with burn sizes ranging from 3% to 92% total body surface area) were
      selected by use of a stratified random sampling technique. Ten of the 14 scales
      are significantly different (p < 0.05, paired t) from the reference population in
      the Vineland manual. The Vineland scores indicate that parents view their burned
      children as being less personally or socially sufficient. Subjects with
      significant behavior problems as measured by use of the CBCL (T score > or = 60)
      differed from their peers with fewer problems by having less overall adaptive
      behavior (p = 0.07), fewer coping skills (p = 0.06), and significantly more
      maladaptive behavior (p = 0.005). The Vineland adaptive behavior domains
      correlated positively with the CBCL total competence scores, whereas the Vineland
      maladaptive behavior correlated positively with the CBCL total behavior score.
      Although it supports previous findings that parents of burned children see them
      as having problems after burn, this study elaborates on and differentiates among
      their difficulties in adapting to their life situations. These findings not only
      affirm the importance of attending to parental perceptions of burned children but
      also identify specific areas to be targeted for psychosocial rehabilitation of
      burned children.

PMID- 8537424
TI  - Burn units' share of Canada's total burn care.
AB  - The share of total hospital Canadian burn care provided by 17 of Canada's 27
      present burn units increased marginally to 18.3% in 1991 from 17.0% in 1981 (p =
      0.0506), and the mortality rate decreased from 5.6% in 1981 to 3.5% in 1991 (p <
      0.05). In 10 units providing serial data, patients with burns undergoing
      ventilation therapy for a concomitant smoke inhalation injury increased from 6.3%
      (n = 58) of 1981 admissions to 11.1% (n = 73) of 1991 admissions (p < 0.05). In
      1991 Canada's 27 burn units treated 32.4% of Canada's hospitalized patients with
      burns and provided 50.6% of hospital burn care days. Although the total number of
      patients with burns hospitalized in Canada decreased by 35% from 7923 in 1981 to
      5161 in 1991 (32.6 to 18.9 per 100,000 population), with a proportional decrease
      in patients treated in burn units, the requirement for intensive care unit
      capability to treat patients undergoing ventilation therapy has remained the same
      or is greater and must be preserved as burn units shrink.

PMID- 8537425
TI  - Overwhelming postsplenectomy sepsis in a patient with burns: a case report and a
      rational approach to treatment.
AB  - Overwhelming postsplenectomy sepsis is a dreaded sequel of splenectomy. The rate
      of overwhelming sepsis in children after splenectomy for trauma is reported to be
      10 to 30 times that of the general population. Episodes of pneumonia, septicemia,
      and meningitis in adults after a splenectomy are 166 times more common than in
      the general population. The care of a patient with burns and asplenia presents
      many unique management challenges to the burn physician. Awareness of the
      development of overwhelming postsplenectomy sepsis and its most common infecting
      organisms is crucial. The specific immunologic deficiencies of reduced
      immunoglobulin production and cell-mediated immunity that exist in patients after
      a splenectomy may be compounded by burn injury. Specific treatment
      recommendations for patients with burns and asplenia are lacking. We report a
      fatal case of overwhelming sepsis in a patient with asplenia and with an 8% total
      body surface area partial-thickness burn, and we review the pathogenesis of
      overwhelming postsplenectomy sepsis. We focus on treatment recommendations
      regarding the use of prophylactic antimicrobials, intravenous immunoglobulin
      replacement therapy, and pneumococcal polyvalent vaccine to standardize the care
      of the patient with burns and asplenia and reduce infectious morbidity and
      deaths.

PMID- 8537426
TI  - Management of skin-grafted burn wounds with Xeroform and layers of dry coarse
      mesh gauze dressing results in excellent graft take and minimal nursing time.
AB  - The goals of postoperative treatment for split-thickness skin grafts (STSGs) are
      to maintain graft integrity, prevent graft and wound desiccation, and minimize
      infections. As we documented in a telephone survey of 16 burn centers, dressings
      for skin grafts usually consist of multiple layers of coarse-mesh gauze; the
      dressings receive frequent applications of aqueous solutions that contain
      antimicrobial agents to control bacterial growth and to maintain a moist
      environment at the wound surface. We prospectively studied the efficacy of our
      standard dressing of one layer of Xeroform (Kendall Inc., Mansfield, Mass.),
      which consists of fine-mesh gauze impregnated with bismuth tribromophenate,
      applied to the STSG surface followed by layers of dry gauze dressings wrapped in
      Kerlix (Kendall Inc.); the entire dressings were left intact until postoperative
      day 5. We evaluated 142 STSGs on 100 patients, mean age 29.2 years (range 0.3 to
      79 years), with burns of 0.5% to 60% total body surface area (mean 9.1%). Meshed
      or sheet STSGs of 0.5% to 18% total body surface area (mean 3.14%) were placed on
      deep partial- or full-thickness excised wounds. Xeroform, followed by coarse-mesh
      gauze dressing, was applied after skin grafts were completed. The entire dressing
      was left intact until the initial takedown-to-graft at 5 days. Patients' grafts
      were evaluated on postoperative day 5 for the percentage of "take" and subgraft
      fluid collected; this evaluation was then repeated every other day for 10 days.
      On postoperative day 5 evaluations, mean skin graft take in all patients was
      98.54% +/- 0.72%. Xeroform and coarse-mesh gauze dressings used to cover STSGs
      and left intact for 5 days until the initial dressing change, resulted in highly
      successful graft outcomes, with minimal postoperative nursing care compared with
      other dressing methods for skin grafts.

PMID- 8537427
TI  - The Vancouver Scar Scale: an administration tool and its interrater reliability.
AB  - The Burn Scar Index, often called the Vancouver Scar Scale, is widely used in
      clinical practice and research to document change in scar appearance. Several
      sections of the Index require equipment to accurately score the items.
      Additionally, the numeric scores are difficult to remember. We recently devised a
      pocket-sized tool to aid in scoring the scar and to increase staff compliance in
      use of the Index. With this tool interrater reliability is good, which makes the
      Burn Scar Index a viable measure for research.

PMID- 8537428
TI  - Quality burn rehabilitation: cost-effective approach.
AB  - As funding for health care becomes a national concern, and workman's compensation
      and private health insurance companies attempt to limit their expenditures in the
      treatment of the client with burns, it may become the responsibility of the burn
      specialists to create a cost-effective approach to quality burn rehabilitation.
      Our outpatient rehabilitation program has taken a cost-effective approach that
      limits the use of inpatient rehabilitation, emphasizes the burn team guiding the
      client to a quick functional return to home and work, and concentrates costs for
      therapy rather than room and board. This cost-effective rehabilitation approach
      emphasizes an intensive 6-hours-per day, 5-days-per-week outpatient program that
      begins immediately after discharge. In a 2 1/2-year follow-up of this cost
      effective program, the following were identified. (1) A 40% reduction in costs
      for third-party payers and (2) clients returning to work an average of 4 months
      after their injury. In the cost-effective rehabilitation approach, 82% of the
      health care costs are concentrated for therapy. In the traditional inpatient
      rehabilitation program, room and board costs comprise 57% of the charges. Because
      it is the responsibility of the burn specialists to educate the health care
      payers, a program description to implement the cost-effective approach to burn
      rehabilitation is provided.

PMID- 8537429
TI  - Fabrication of total-contact burn masks by use of human body topography and
      computer-aided design and manufacturing.
AB  - Total-contact burn masks are used to treat scar tissue hypertrophy of the face.
      The mask should conform very closely to the contours of the face and provide
      evenly distributed pressure. The mask is worn continually throughout wound
      maturation. Lack of fit because of an inability to obtain exact facial contours
      by use of an alginate material diminishes the effectiveness of the mask. A
      multidisciplinary team representing physical therapy, CAD/CAM (computer-aided
      design and computer-aided manufacturing), biomedical engineering, and prosthetics
      has advanced the method of developing total-contact burn masks by use of human
      body electronic imaging, computer graphics, and numerically controlled milling
      processes. High-resolution surface scanning and CAD/CAM have been used
      successfully to accurately fabricate three such masks. The methodology and
      preliminary results from use of these state-of-the-art techniques are described
      in this article.

PMID- 8537430
TI  - Finding homes without smoke detectors: one step in planning burn prevention
      programs.
AB  - Residential fires are the leading cause of burn-related deaths in the United
      States. Smoke detectors could save many of these lives. A 1993 telephone survey
      of 661 Kentucky households included questions on residential smoke detectors.
      Statewide, 16.4% of households did not possess a functioning smoke detector;
      however, in nonmetropolitan Appalachian counties, 30.5% of households lacked
      detectors. Characteristics associated with lack of a functioning smoke detector,
      as determined by multivariate logistic regression, were as follows: living in a
      nonapartment dwelling (odds ratio [OR] = 4.14, 95% confidence interval [CI] =
      1.42 to 12.01); having an annual household income of $20,000 or less (OR = 2.34,
      CI = 1.49 to 3.68); being unmarried (OR = 1.73, CI = 1.12 to 2.69); living alone
      (OR = 1.69, CI = 1.02 to 2.80); and living in a nonmetropolitan county (OR =
      1.68, CI = 1.05 to 2.69). Knowledge of these population-based characteristics can
      assist planners of burn prevention programs to target at-risk populations.

PMID- 8537431
TI  - Inconsistencies in psychosocial assessment of children after severe burns.
AB  - Health care providers usually except children with severe burns to have
      psychosocial problems due to the severity of the injuries and resulting
      deformities. To test the validity of that expectation, 72 children (43 boys, 29
      girls) who had suffered severe burns were assessed at least 1 year after burn
      injury for behavior problems and competence, by use of the 1991 Achenbach
      questionnaires: Child Behavior Checklist (CBCL), Youth Self-Report, and Teacher
      Report Form. The scores on each questionnaire then were compared by use of paired
      t tests. Also, the scores of the patient population were compared with those of
      the nonreferred reference populations provided by Achenbach. Compared with the
      Teacher Report Form and Youth Self-Report, the CBCL revealed a statistically
      significant (p < 0.05) greater number of behavior problems and lower level of
      competence for all age groups and both sexes. Item analysis revealed in most
      instances excess endorsement of specific items on all scales for the patient
      population compared with their respective reference populations, but more items
      were endorsed on the CBCL. These results could be explained by increased parental
      sensitivity to problem behavior or decreased competence of their children after
      severe burns. Further studies are needed to understand the discrepancies between
      the CBCL and the other scales.

PMID- 8537432
TI  - A chromomeric model for nuclear and chromosome structure.
AB  - The basic structural elements of chromatin and chromosomes are reviewed. Then a
      model involving only three architectural motifs, nucleosomes, chromatin loops and
      transcription factories/chromomeres, is presented. Loops are tied through
      transcription factors and RNA polymerases to factories during interphase and to
      the remnants of those factories, chromomeres, during mitosis. On entry into
      mitosis, increased adhesiveness between nucleosomes and between factories drives
      a 'sticky-end' aggregation to the most compact and stable structure, a cylinder
      of nucleosomes around an axial chromomeric core.

PMID- 8537433
TI  - arc6, an extreme chloroplast division mutant of Arabidopsis also alters
      proplastid proliferation and morphology in shoot and root apices.
AB  - The arc6 (accumulation and replication of chloroplasts) mutant of Arabidopsis has
      only two greatly enlarged chloroplasts per mature leaf mesophyll cell compared
      with ninety chloroplasts per cell in the wild type. The mutation is a single
      nuclear gene and the plant phenotype is normal. Shoot and root apical meristems
      of arc6 plants have been examined to determine how early during plastid
      development the mutant arc6 phenotype can be recognised. In the cells of the arc6
      apical meristem there are only two proplastids, which are larger than wild type
      with a highly variable morphology. In the cells of the leaf primordia where
      differentiation of proplastids to chloroplasts occurs arc6 plastids are larger
      and at a more advanced developmental stage than wild-type plastids. In arc6 root
      cells statoliths and other plastids also show grossly abnormal morphology and the
      statoliths are greatly increased in size. During arc6 stomatal guard cell
      development the perturbation in proplastid population dynamics affects plastid
      segregation and 30% of stomata lack plastids in one or both guard cells. Our
      evidence would suggest that ARC6 is expressed throughout the vegetative cells of
      the Arabidopsis seedling with major effects on both the proplastid phenotype and
      the proplastid population. ARC6 is the first gene to be identified in Arabidopsis
      which has a global effect on plastid development in cells arising from both the
      shoot and root meristems, and is of major importance in the nuclear control of
      plastid differentiation in higher plants.

PMID- 8537434
TI  - Functional conservation of the cell cycle-regulating transcription factor
      DRTF1/E2F and its pathway of control in Drosophila melanogaster.
AB  - The cellular transcription factor DRTF1/E2F is implicated in the control of early
      cell cycle progression due to its interaction with important regulators of
      cellular proliferation, such as pocket proteins (for example, the retinoblastoma
      tumour suppressor gene product), cyclins and cyclin-dependent kinase subunits. In
      mammalian cells DRTF1/E2F is a heterodimeric DNA binding activity which arises
      when a DP protein interacts with an E2F protein. Here, we report an analysis of
      DRTF1/E2F in Drosophila cells, and show that many features of the pathway which
      regulate its transcriptional activity are conserved in mammalian cells, such as
      the interaction with pocket proteins, binding to cyclin A and cdk2, and its
      modulation by viral oncoproteins. We show that a Drosophila DP protein which can
      interact co-operatively with E2F proteins is a physiological DNA binding
      component of Drosophila DRTF1/E2F. An analysis of the expression patterns of a
      Drosophila DP and E2F protein indicated that DmDP is developmentally regulated
      and in later embryonic stages preferentially expressed in proliferating cells. In
      contrast, the expression of DmE2F-1 in late stage embryos occurs in a restricted
      group of neural cells, whereas in early embryos it is widely expressed, but in a
      segmentally restricted fashion. Some aspects of the mechanisms which integrate
      early cell cycle progression with the transcription apparatus are thus conserved
      between Drosophila and mammalian cells. The distinct expression patterns of DmDP
      and DmE2F-1 suggest that the formation of DP/E2F heterodimers, and hence
      DRTF1/E2F, is subject to complex regulatory cues.

PMID- 8537435
TI  - A transient association of gamma-tubulin at the midbody is required for the
      completion of cytokinesis during the mammalian cell division.
AB  - gamma-Tubulin, a relatively new member of the tubulin gene family, is localized
      primarily at the centrosome throughout the mammalian cell cycle and may play a
      key role in nucleation of cellular microtubule assembly. A transient association
      of gamma-tubulin at the cytoplasmic bridge of telophase mammalian cells, the
      midbody, is recently documented. Using immunogold electron microscopy and serial
      section reconstruction analysis, we show here that the transiently associated
      midbody gamma-tubulin is localized at the minus ends of microtubules in the
      midbody structure. Using antisense RNA methods we also demonstrate that a
      selective depletion of transiently associated midbody gamma-tubulin causes an
      abortive cytokinesis due to a failure in the morphogenesis of the midbody
      structure.

PMID- 8537436
TI  - Mapping of nucleoporins to the center of the nuclear pore complex by post
      embedding immunogold electron microscopy.
AB  - Ultrathin sections of Lowicryl K4M embedded cultured 3T3 cells, human
      keratinocytes and mouse/rat liver tissue were incubated with polyspecific primary
      antibodies against p62 and other nucleoporins followed by 10 nm gold labeled
      secondary antibodies. By quantitatively evaluating both cross sections and
      tangential sections of the NPC, we found that irrespective of the cell type
      antibodies predominantly bound within a radius of 25 nm around the central axis
      of the nuclear pore complex (NPC). Superposition of a current structural model of
      the NPC with the nucleoporin distribution observed by us showed that nucleoporins
      mapped predominatly to the controversely discussed 'central granule'. Our
      experimental approach was verified by mapping gp210, another nuclear pore
      protein, at or very close to the NPC in the perinuclear cisterna thus
      establishing a distribution pattern completely different from that of the
      nucleoporins.

PMID- 8537437
TI  - Involvement of M-cadherin in terminal differentiation of skeletal muscle cells.
AB  - Cadherins are a gene family encoding calcium-dependent cell adhesion proteins
      which are thought to act in the establishment and maintenance of tissue
      organization. M-cadherin, one member of the family, has been found in myogenic
      cells of somitic origin during embryogenesis and in the adult. These findings
      have suggested that M-cadherin is involved in the regulation of morphogenesis of
      skeletal muscle cells. Therefore, we investigated the function of M-cadherin in
      the fusion of myoblasts into myotubes (terminal differentiation) in cell culture.
      Furthermore, we tested whether M-cadherin might influence (a) the expression of
      troponin T, a typical marker of biochemical differentiation of skeletal muscle
      cells, and (b) withdrawal of myoblasts from the cell cycle (called terminal
      commitment). The studies were performed by using antagonistic peptides which
      correspond to sequences of the putative M-cadherin binding domain. Analogous
      peptides of N-cadherin have previously been shown to interfere functionally with
      the N-cadherin-mediated cell adhesion. In the presence of antagonistic M-cadherin
      peptides, the fusion of myoblasts into myotubes was inhibited. Analysis of
      troponin T revealed that it was downregulated at the protein level although its
      mRNA was still detectable. In addition, withdrawal from the cell cycle typical
      for terminal commitment of muscle cells was not complete in fusion-blocked
      myogenic cells. Finally, expression of M-cadherin antisense RNA reducing the
      expression of the endogenous M-cadherin protein interfered with the fusion
      process of myoblasts. Our data imply that M-cadherin-mediated myoblast
      interaction plays an important role in terminal differentiation of skeletal
      muscle cells.

PMID- 8537438
TI  - Ligand-stimulated beta 2-adrenergic receptor internalization via the constitutive
      endocytic pathway into rab5-containing endosomes.
AB  - The small GTPase rab5 appears to be rate-limiting for the constitutive
      internalization of transferrin receptor and for fluid-phase endocytosis. However,
      it is unknown whether rab5 regulates receptors whose internalization is
      stimulated by the binding of ligand, and whether such receptors change the
      underlying rate of the endocytic pathways they utilize. As a model for ligand
      stimulated endocytosis, we used transfected HEK293 cells expressing high levels
      of an epitope-tagged human beta 2-adrenergic receptor. Nearly all receptors were
      on the cell surface in the absence of agonist, but within ten minutes of agonist
      addition > 50% of receptors internalized and colocalized extensively with rab5.
      Hypertonic sucrose blocked beta 2-adrenergic receptor internalization, as well as
      that of transferrin receptor, suggesting a clathrin-mediated process. In
      contrast, an inhibitor of potocytosis had little effect upon beta 2-adrenergic
      receptor internalization, suggesting that this process did not require active
      caveolae. Consistent with this finding, caveolin was not detectable in the 12
      beta 6 line, as assessed by western blotting with a polyclonal anti-caveolin
      antibody. Stimulated receptor internalization did not affect the rate or capacity
      of the constitutive endocytic pathway since there was no detectable increase in
      fluid-phase endocytosis after addition of beta-agonist, nor was there a
      significant change in the amount of surface transferrin receptor. Altogether,
      these data suggest that beta 2-adrenergic receptors internalize by a clathrin
      mediated and rab5-regulated constitutive endocytic pathway. Further, agonist
      stimulated receptor internalization has no detectable effect upon the function of
      this pathway.

PMID- 8537439
TI  - Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial
      and glandular tissues.
AB  - It was shown recently that water channel homologs MIWC (mercurial insensitive
      water channel) and GLIP (glycerol intrinsic protein) colocalized in basolateral
      membranes of kidney collecting duct, tracheal and colonic epithelia, and in brain
      pia mater. We report here an extensive immunolocalization study of MIWC and GLIP
      in non-epithelial and glandular epithelial tissues in rat. Immunogold electron
      microscopy confirmed colocalization of MIWC and GLIP in basolateral membrane of
      principal cells in kidney collecting duct. However, in other epithelia, MIWC but
      not GLIP was expressed in basolateral membrane of parietal cells in stomach, and
      in excretory tubules of salivary and lacrimal glands; GLIP but not MIWC was
      expressed in transitional epithelium of urinary bladder and skin epidermis. In
      the central nervous system, MIWC was strongly expressed in the ependymal layer
      lining the aqueductal system, and in astrocytes throughout the spinal cord and in
      selected regions of brain. MIWC was also expressed in a plasma membrane pattern
      in skeletal, but not smooth or cardiac muscle. Neither protein was expressed in
      small intestine, testis, liver, spleen and nerve. The tissue-specific expression
      of MIWC suggests a role in fluid transport and/or cell volume regulation in
      stomach and glandular epithelia. The functional role of MIWC expression in the
      neuromuscular system and of GLIP expression in skin and urinary bladder is
      uncertain. The specific cellular sites of MIWC expression (astrocytes, trachea,
      sarcolemma, gastric parietal cells and kidney principal cells) correspond exactly
      to sites where orthogonal arrays of particles (OAPs) have been visualized by
      freeze-fracture electron microscopy, suggesting that MIWC may be the OAP protein.

PMID- 8537440
TI  - Localization of the glucocorticoid receptor in discrete clusters in the cell
      nucleus.
AB  - The cell nucleus is highly organized. Many nuclear functions are localized in
      discrete domains, suggesting that compartmentalization is an important aspect of
      the regulation and coordination of nuclear functions. We investigated the
      subnuclear distribution of the glucocorticoid receptor, a hormone-dependent
      transcription factor. By immunofluorescent labeling and confocal microscopy we
      found that after stimulation with the agonist dexamethasone the glucocorticoid
      receptor is concentrated in 1,000-2,000 clusters in the nucleoplasm. This
      distribution was observed in several cell types and with three different
      antibodies against the glucocorticoid receptor. A similar subnuclear distribution
      of glucocorticoid receptors was found after treatment of cells with the
      antagonist RU486, suggesting that the association of the glucocorticoid receptor
      in clusters does not require transformation of the receptor to a state that is
      able to activate transcription. By dual labeling we found that most dexamethasone
      induced receptor clusters do not colocalize with sites of pre-mRNA synthesis. We
      also show that RNA polymerase II is localized in a large number of clusters in
      the nucleus. Glucocorticoid receptor clusters did not significantly colocalize
      with these RNA polymerase II clusters or with domains containing the splicing
      factor SC-35. Taken together, these results suggest that most clustered
      glucocorticoid receptor molecules are not directly involved in activation of
      transcription.

PMID- 8537441
TI  - Monoclonal and polyclonal antibodies detect a new type of post-translational
      modification of axonemal tubulin.
AB  - Polyclonal (PAT) and monoclonal (AXO 49) antibodies against Paramecium axonemal
      tubulin were used as probes to reveal tubulin heterogeneity. The location, the
      nature and the subcellular distribution of the epitopes recognized by these
      antibodies were, respectively, determined by means of: (i) immunoblotting on
      peptide maps of Paramecium, sea urchin and quail axonemal tubulins; (ii)
      immunoblotting on ciliate tubulin fusion peptides generated in E. coli to
      discriminate antibodies directed against sequential epitopes (reactive) from post
      translational ones (non reactive); and (iii) immunofluorescence on Paramecium
      cells, using throughout an array of antibodies directed against tubulin sequences
      and post-translational modifications as references. AXO 49 monoclonal antibody
      and PAT serum were both shown to recognize epitopes located near the carboxyl
      terminal end of both subunits of Paramecium axonemal tubulin, whereas the latter
      recognized additional epitopes in alpha-tubulin; AXO 49 and a fraction of the PAT
      serum proved to be unreactive over fusion proteins; both PAT and AXO 49 labelled
      a restricted population of very stable microtubules in Paramecium, consisting of
      axonemal and cortical ones, and their reactivity was sequentially detected
      following microtubule assembly; finally, both antibodies stained two upward
      spread bands in Paramecium axonemal tubulin separated by SDS-PAGE, indicating the
      recognition of various alpha- and beta-tubulin isoforms displaying different
      apparent molecular masses. These data, taken as a whole, definitely establish
      that PAT and AXO 49 recognize a post-translational modification occurring in
      axonemal microtubules of protozoa as of metazoa. This modification appears to be
      distinct from the previously known ones, and all the presently available evidence
      indicates that it corresponds to the very recently discovered polyglycylation of
      Paramecium axonemal alpha- and beta-tubulin.

PMID- 8537442
TI  - Characterization of a 5.4 kb cDNA fragment from the Z-line region of rabbit
      cardiac titin reveals phosphorylation sites for proline-directed kinases.
AB  - Titin is an approximately 3 MDa protein that spans from the M- to the Z-line in
      the sarcomeres of vertebrate striated muscle. The protein is presumably encoded
      by unusually large mRNAs of 70-80 kb. Although titin has been studied by several
      laboratories, barely more than half of the cDNA sequence (approximately 45 kb)
      has been published, most of it obtained from the A-band and M-line region
      (corresponding to the C-terminal half of the molecule). A special cDNA library
      was constructed using size selected total RNA from adult rabbit cardiac muscle in
      order to obtain sequence data from titin's unknown N-terminal region. A
      monoclonal antibody (T12), which binds to an epitope close to the Z-line, was
      used to identify initial cDNA clones. Additional overlapping clones were isolated
      and sequenced yielding a 5.4 kb contig. The encoded polypeptide contains 16 Type
      II domains and four unique intervening segments. Polyclonal sera, raised against
      an expressed protein fragment encoded by the 5' end of the contig, strongly
      stained the Z-line of myofibrils of different species. However, the sequence of
      this fragment is 83% identical at the amino acid level with the previously
      reported C-terminal (i.e. M-line) end of chicken embryonic skeletal muscle titin.
      The expressed protein fragment could be phosphorylated in vitro by embryonic
      skeletal muscle extract and by the purified proline-directed kinase ERK1,
      presumably at the xSPxR recognition sites located in the first interdomain
      segment.

PMID- 8537443
TI  - Intracellular transport of the murine leukemia virus during acute infection of
      NIH 3T3 cells: nuclear import of nucleocapsid protein and integrase.
AB  - The entry and intracellular transport of Moloney-murine leukemia virions inside
      mouse NIH 3T3 cells have been followed by electron microscopy techniques. Five
      viral proteins--matrix (MA, p15), capsid (CA, p30), nucleocapsid (NC, p10),
      integrase (IN), and the envelope glycoprotein (SU, gp70)--were located by
      immunolabeling using gold probes. After entering the cells, viral particles were
      frequently detected inside cytoplasmic vesicles of variable size. Their viral
      envelope was apparently lost during intracytoplasmic transport. When the
      unenveloped viral cores reached the nuclear membrane or its vicinity, they were
      disrupted. Two of the immunolabeled proteins, NC and IN, were detected entering
      the nucleus of non-dividing cells, where both were targeted to the nucleolus.
      However, MA and CA were found only in the cytoplasm. NC is a nucleic acid-binding
      protein which contains potential nuclear localization signals. We suggest that NC
      could enter the nucleus as part of a nucleoprotein complex, associated with IN,
      and possibly, also with viral DNA.

PMID- 8537444
TI  - Osteoclast ATP receptor activation leads to a transient decrease in intracellular
      pH.
AB  - Application of extracellular adenosine triphosphate (ATP) induces a pulsed
      decrease in osteoclast intracellular pH (pHi), as measured with
      seminaphthofluorescein (SNAFL)-calcein on a laser scanning confocal microscope.
      Adenosine diphosphate also produces a pHi decrease, but adenosine monophosphate,
      uridine triphosphate, 2-methylthio-ATP, and beta, gamma-methylene-ATP have little
      effect on pHi. The ATP-induced pHi decrease is largely inhibited by suramin, a P2
      purinergic receptor blocker. Clamping intracellular free [Ca2+] ([Ca2+]i) with
      BAPTA/AM does not affect the ATP-induced pHi change, showing that this pHi
      decrease is not caused by the increased intracellular [Ca2+]i that is produced by
      activation of osteoclast purinergic receptors. We show that an increase in
      [Ca2+]i by itself will produce a pHi increase. The ATP effect is not blocked by
      inhibition of Na+/H+ exchange by either Na(+)-free bathing medium or amiloride.
      Two inhibitors of the osteoclast cell membrane proton pump, N-ethylmaleimide and
      vanadate, produce partial inhibition of the ATP-induced pHi decrease. Two other
      proton pump inhibitors, bafilomycin and N,N'-dicyclohexylcarbodiimide, have no
      influence on the ATP effect. None of the proton pump inhibitors but vanadate has
      a direct effect on pHi. Vanadate produces a transient pHi increase upon
      application to the bathing medium, possibly as a result of its known effect of
      stimulating the Na+/H+ exchanger. Inhibition of Cl-/HCO3- exchange by decreasing
      extracellular Cl- gives a pronounced long-term pHi increase, supporting the
      hypothesis that this exchange has an important role in osteoclast pHi
      homeostasis. In Cl(-)-free extracellular medium, there is a greatly reduced
      effect of extracellular ATP on pHi.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537445
TI  - The response to thrombin of human neutrophils: evidence for two novel receptors.
AB  - Human alpha-thrombin was a chemoattractant for human neutrophils yielding a
      maximal response of similar magnitude to that observed with formyl-Met-Leu-Phe.
      The observed chemotaxis was not due to stimulation of the proteolytically
      activated thrombin receptor since: (1) this receptor was not detected by flow
      cytometry; (2) the inactive thrombin mutant Ser195-->Ala elicited a chemotactic
      response indistinguishable from that caused by wild-type thrombin; (3) antibodies
      to the cleavage site of the proteolytically activated receptor did not affect
      thrombin-induced chemotaxis; (4) a thrombin receptor activating peptide (TRAP)
      failed to stimulate chemotaxis. These data indicate the existence of a thrombin
      receptor for neutrophil chemotaxis which is not activated by proteolysis. In
      addition, although wild-type and ser195-->Ala thrombin did not cause an increase
      in intracellular Ca2+, a Ca2+ response to TRAP was observed with neutrophils from
      some donors. The TRAP-induced increase in Ca2+ was reproducible, dose dependent
      and specific. The use of alanine-substituted peptides demonstrated that the Ca2+
      response was due to TRAP stimulation of a receptor other than the proteolytically
      activated thrombin receptor. Thus, it is necessary to re-evaluate the assumption
      made in previous studies that responses to TRAP are mediated by the
      proteolytically activated thrombin receptor.

PMID- 8537446
TI  - Differential distribution of two cytoplasmic variants of the alpha 6 beta 1
      integrin laminin receptor in the ventral plasma membrane of embryonic
      fibroblasts.
AB  - The integrin alpha 6 beta 1 is a receptor involved in the adhesion of several
      cell types to laminin. By using function-blocking antibodies, we have shown that
      alpha 6 beta 1 is a functional laminin receptor in chick embryo fibroblasts. We
      also found that these cells express two variants of the alpha 6 subunit, alpha 6A
      and alpha 6B, characterized by different cytoplasmic domains. By using indirect
      immunofluorescence with isoform-specific polyclonal antibodies, we showed that
      the two isoforms of the alpha 6 subunit distribute differently on the ventral
      plasma membrane of these cells cultured on laminin-coated substrates. In fact,
      while the alpha 6A subunit was found codistributing with vinculin in focal
      contacts, the alpha 6B subunit showed a homogeneously distributed punctate
      pattern. This difference was particularly evident when preparations of ventral
      plasma membranes were used for the immunolocalization. Furthermore, when cells
      were cultured on fibronectin, a substrate not recognized by the alpha 6 beta 1
      laminin receptor, the distribution of the two alpha 6 isoforms was similar to
      that observed on laminin, with alpha 6A still colocalizing with vinculin in focal
      adhesions. Our results indicate that two forms of the alpha 6 beta 1 laminin
      receptor coexpressed in the same cells show distinctive distributions, and
      suggest that receptor occupancy by laminin is not essential for the accumulation
      of the alpha 6A beta 1 integrin in adhesion plaques.

PMID- 8537448
TI  - Purification of bovine lens cell-to-cell channels composed of connexin44 and
      connexin50.
AB  - Cell-to-cell channels composed of connexin44 and connexin50 were purified from
      plasma membranes of calf and fetal bovine lenses. The channels were treated with
      the nonionic detergents octyl-beta-D-glucopyranoside and decyl-beta-D
      maltopyranoside, and the channel/detergent complexes purified by ion and gel
      filtration column chromatography. In negative staining, the channels appeared as
      annuli 11 +/- 0.6 nm (s.d., n = 105) in diameter and as 16 +/- 0.8 nm (s.d., n =
      96) long particles which corresponded to top and side views of 'complete' cell-to
      cell channels. The purified cell-to-cell channels were composed principally of a
      protein, called MP70, that appeared as a diffuse 55-75 kDa band in SDS-PAGE.
      Dephosphorylation with alkaline phosphatase transformed the diffuse 55-75 kDa
      band into two distinct bands of almost equal intensity. Immunoblotting showed the
      bands to be connexin44 and connexin50, respectively. The antibodies also
      recognized weaker bands composed of the unphosphorylated form of both connexins.
      The connexins appear to be processed independently 'in vivo'. The
      unphosphorylated form of connexin50 was present in channels and membranes from
      fetal, calf and adult bovine lenses, while unphosphorylated connexin44 only in
      channels purified from fetal lenses. Therefore, lens cell-to-cell channels are
      composed principally of equal amounts of phosphorylated connexins 44 and 50 that
      appear to be assembled in the same channel ('hybrid').

PMID- 8537447
TI  - Cyclic AMP modifies the cellular distribution of connexin43 and induces a
      persistent increase in the junctional permeability of mouse mammary tumor cells.
AB  - Direct communication between cells via gap junctions is thought to be an
      important component of homeostasis and coordinated cellular responses to external
      signals. We investigated how the second messenger cAMP exerts its effects on
      junctional communication in a mouse mammary tumor cell line, MMT22. Junctional
      permeance was quantitatively assessed using dye microinjection and video
      microscopy. An increase of permeance was found after exposure to 8-bromo-cAMP,
      being detectable after 30 minutes of treatment and attaining a fourfold higher
      level of permeance by 24 hours. This elevated level was maintained with
      continuous exposure to 8-bromo-cAMP for seven days. The permeability change was
      accompanied by an increase in gap junctions as shown by freeze-fracture electron
      microscopy and by confocal microscopy using antibodies directed against the gap
      junction protein, connexin43. The amount of detergent-insoluble connexin43 also
      increased with 8-bromo-cAMP treatment, and most of the increase could be
      attributed to an increase of slower migrating (i.e. phosphorylated) species of
      connexin43. However, connexin43 mRNA and the total cellular content of connexin43
      did not change over this period of exposure to 8-bromo-cAMP, as shown by
      densitometric analyses of northern and western blots. We conclude that 8-bromo
      cAMP affects the distribution of connexin43 such that a greater proportion of the
      protein is utilized for channel formation. Since these changes were relatively
      slow to develop and persisted with prolonged exposure to 8-bromo-cAMP, it is
      possible that the junctional permeability of these mammary tumor cells is linked
      to the 'basal' level of cAMP, i.e. levels maintained by the cells in accordance
      with a particular cell state.

PMID- 8537449
TI  - Distinct heparin-binding and neurite-promoting properties of laminin isoforms
      isolated from chick heart.
AB  - Laminin isolated from chick heart is composed of several heterotrimeric variants
      of 800 and 700 kDa. Here, we used monoclonal antibodies against chick laminin to
      purify different laminin isoforms from this mixture. Antibody 8D3 specifically
      removed laminin containing alpha 2 chain from chick heart laminin preparations,
      leaving behind 700 kDa variants. Using antibody C4 against the laminin beta 2
      chain, alpha 2 chain containing variants were further separated into alpha 2 beta
      1 gamma 1 and alpha 2 beta 2 gamma 1 laminin, respectively. Laminins containing
      alpha 2 chain and recognized by antibody 8D3 are cross-shaped molecules. Their
      expression during embryogenesis is tightly regulated. In 5-day embryos staining
      with monoclonal antibody 8D3 is restricted to the dermamyotome. Older embryos (8
      days) express alpha 2 chain containing variants at myotendinous junction
      primordia of skeletal muscle, and only late in development these variants are
      generally expressed in skeletal and heart muscle basement membranes. The 700 kDa
      laminin variants contain beta 1, beta 2, and gamma 1 subunits affiliated with an
      immunologically distinct, shorter alpha x chain and appear to be T-shaped in the
      electron microscope. Whereas laminins with an alpha 2 subunit bind to heparin,
      variants with the novel alpha x chain do not. Experiments using cultured
      sympathetic neurons showed that laminins with alpha x chain are less potent than
      alpha 2 chain containing variants in promoting neurite outgrowth. In contrast,
      sympathetic neurons cannot discriminate between alpha 2 beta 1 gamma 1 and alpha
      2 beta 2 gamma 1 laminin substrates, respectively, and show identical high rates
      of neurite formation.

PMID- 8537450
TI  - DNA polymerase alpha, a component of the replication initiation complex, is
      essential for the checkpoint coupling S phase to mitosis in fission yeast.
AB  - Genetic analysis in the yeast Schizosaccharomyces pombe has shown that three
      genes cdc18, cut5, and cdt1, are essential for DNA synthesis and also for the
      checkpoint control that couples completion of DNA replication to the onset of
      mitosis. To test whether assembly of the replication initiation complex is an
      important element in the checkpoint control pathway we have investigated if DNA
      polymerase alpha (pol1), a component of the initiation complex, is essential for
      the S-phase checkpoint control. We show that germinating S. pombe spores
      disrupted for the pol1 gene enter mitosis despite defects in DNA synthesis. This
      is shown by monitoring septation index, DNA content, and by direct
      immunofluorescence of mitotic spindles using antibodies to alpha-tubulin. In
      addition we have isolated six temperature sensitive mutants in the pol1 gene that
      cause cell cycle arrest when grown at the nonpermissive temperature. Our
      experiments support a model in which DNA polymerase alpha, in addition to being
      part of the initiation complex, is required for a checkpoint signal that is
      activated as cells traverse START, and is essential to prevent mitosis until S
      phase has been completed. In contrast, proteins responsible for the elongation of
      DNA may not be necessary for this checkpoint signal.

PMID- 8537451
TI  - Cell adhesion in sponges: potentiation by a cell surface 68 kDa proteoglycan
      binding protein.
AB  - Constitutive, stable intercellular adhesion is one of the distinguishing
      properties of metazoans, of which the sponges (Phylum Porifera) are the most
      primitive representatives. In sponges, intercellular adhesion is mediated by the
      large proteoglycan-like cell agglutinating molecule 'aggregation factor', which
      binds to cell surfaces via an oligosaccharide moiety. Previous studies indicated
      that this aggregation factor binds to two proteins associated with the surface of
      sponge cells. One of these, a 68 kDa peripheral membrane protein, was isolated by
      affinity chromatography on aggregation factor conjugated to Sepharose. This
      monomeric 68 kDa glycoprotein plays a key role in sponge cell adhesion since it
      potently inhibits the binding of aggregation factor to cell surfaces and
      completely prevents aggregation factor-mediated cell adhesion. The 68 kDa
      aggregation factor ligand binds with high affinity to both aggregation factor (KD
      = 2 x 10(-9) M) and cell surfaces (KD = 6 x 10(-8) M) providing evidence that it
      serves as an intramolecular bridge between the aggregation factor molecule and a
      cell surface receptor. Therefore, this early metazoan protein may represent one
      of the earliest extracellular matrix adhesion proteins to have arisen in the
      course of metazoan evolution.

PMID- 8537452
TI  - CD44 exhibits a cell type dependent interaction with triton X-100 insoluble,
      lipid rich, plasma membrane domains.
AB  - CD44 is an abundant, widely expressed transmembrane glycoprotein which can act as
      a receptor for the extracellular matrix glycosaminoglycan, hyaluronan.
      Biochemical and morphological studies have demonstrated that in fibroblasts a
      significant of the CD44 population is resistant to Triton X-100 extraction and
      that the detergent insoluble protein is co-localized with components of the
      cortical cytoskeleton. Surprisingly, this distribution is not abrogated upon
      deletion of the CD44 cytoplasmic tail indicating that mechanisms other than a
      direct interaction with the cytoskeleton can regulate CD44. In this manuscript,
      the mechanisms underlying this detergent-insoluble association are further
      investigated. There was no evidence that the Triton X-100 insolubility of CD44
      resulted from homotypic aggregation, an association with hyaluronan or from a
      direct, or indirect, association with the cytoskeleton. Instead, evidence is
      presented that the detergent insolubility of fibroblast CD44 at 4 degrees C
      results from an association of the CD44 transmembrane domain with Triton X-100
      resistant, lipid rich, plasma membrane domains. The proportion of the CD44 found
      in these Triton X-100 insoluble structures is dependent upon cell type and cannot
      be altered by changing cell motility or extracellular matrix associations. These
      studies provide evidence for a novel mechanism regulating this adhesion protein
      in the plasma membrane.

PMID- 8537453
TI  - Interphase phosphorylation of the Drosophila nuclear lamin: site-mapping using a
      monoclonal antibody.
AB  - The Drosophila nuclear lamin is highly phosphorylated during interphase. Two
      interphase isoforms, differing in degree of phosphorylation, can be distinguished
      by one-dimensional SDS-polyacrylamide gel electrophoresis. One migrates with an
      apparent mass of 74 kDa (lamin Dm1); the other is more highly phosphorylated and
      migrates as a 76 kDa protein (lamin Dm2). We generated a monoclonal antibody,
      ADL84 which binds to lamin Dm1 but not lamin Dm2. Binding of ADL84 to lamin Dm2
      was restored by phosphatase treatment of immunoblots containing lamins.
      Immunoprecipitation with ADL84 demonstrated that purified Drosophila nuclear
      lamins Dm1 and Dm2 are present as a random mixture of homo- and heterodimers.
      Indirect immunofluorescence experiments suggest that lamin Dm1 is present in all
      Drosophila cell types. The epitope for ADL84 was mapped by analyzing binding to
      bacterially expressed lamin deletion mutants and subsequently by screening for
      point mutants (randomly generated by polymerase chain reaction) which were not
      recognized by ADL84. The ADL84-epitope encompasses amino acids R22PPSAGP
      (arginine 22-proline 28). Peptide competition experiments demonstrated directly
      that phosphorylation of serine 25 impedes lamin binding by ADL84. This suggests
      that serine 25 is the lamin Dm2-specific phosphorylation site.

PMID- 8537454
TI  - The membrane skeleton of acetylcholine receptor domains in rat myotubes contains
      antiparallel homodimers of beta-spectrin in filaments quantitatively resembling
      those of erythrocytes.
AB  - I used immunogold labeling and quick-freeze, deep-etch, rotary replication to
      characterize the membrane skeleton at regions with high concentrations of
      acetylcholine receptor domains in receptor clusters of cultured rat muscle cells.
      This membrane skeleton consists of a network of filaments closely applied to the
      cytoplasmic membrane surface. The filaments are specifically decorated by
      immunogold labeling with a monoclonal antibody, VIIF7, that recognizes an isoform
      of beta-spectrin colocalizing with acetylcholine receptors. The filaments are 32
      +/- 11 nm in length and three to four filaments (average 3.1-3.3) join at each
      intersection to form the network. These parameters are nearly identical to those
      reported previously for the membrane skeleton of erythrocytes. Depending on the
      amount of platinum coating, filament diameters range from 9 to 11 nm in diameter,
      and are 1.4 nm larger on average than spectrin filaments of erythrocytes
      replicated at the same time. Filaments are decorated with gold particles close to
      one end, consistent with the location of the epitope recognized by the monoclonal
      antibody. Computer modeling shows that all filament intersections in the membrane
      skeletal network are equally capable of being labeled by the monoclonal antibody.
      This pattern of labeling is consistent with a network containing antiparallel
      homodimers of beta-spectrin.

PMID- 8537455
TI  - Localization of fruit tree viruses by immuno-tissue printing in infected shoots
      of Malus sp. and Prunus sp.
AB  - Immuno-tissue printing protocols for the localization of apple chlorotic leaf
      spot virus (ACLSV), stem grooving virus (SGV) and plum pox virus (PPV) in shoots
      of Prunus and Malus in vitro have been established for routine diagnosis in a
      virus elimination program. Since these viruses belong to different virus genera,
      the protocols were adapted according to the properties of the virus under
      investigation. Accumulation of ACLSV was highest in the base of the stem and
      decreased towards the apex of the shoots. ACLSV was found in the epidermis, the
      cortex, in the vascular bundles, but seldom in the pith tissue of in vitro apple
      shoots. ACLSV immuno-tissue printing was as sensitive as ELISA and the intensity
      of color signals in immuno-tissue prints correlated with absorbance values by two
      step ELISA. SGV could be detected by immuno-tissue prints at infectivity levels,
      where it reacted negative in ELISA. SGV accumulated in the vascular bundles,
      occurred locally in the parenchymatic tissue, was found in high amounts in young
      leaves near the meristem, but not within the meristem. PPV was detected in all
      tissue types of stem sections with an irregular pattern reflecting the in vivo
      situation causing problems with detection. Discrimination of poorly and heavily
      infected shoots was possible with the naked eye.

PMID- 8537456
TI  - Detection of human coronavirus 229E-specific antibodies using recombinant fusion
      proteins.
AB  - Human coronaviruses are known to be a common cause of respiratory infections in
      man. However, the diagnosis of human coronavirus infections is not carried out
      routinely, primarily because the isolation and propagation of these viruses in
      tissue culture is difficult and time consuming. The aim of this study was to
      evaluate the use of recombinant, bacterial expressed proteins in the
      serodiagnosis of coronavirus infections. Two proteins were examined: the human
      coronavirus 229E nucleocapsid protein (N), expressed as a fusion protein in the
      vector pUR and the coronavirus 229E surface glycoprotein (S), expressed as a
      fusion protein in the vector pROS. The recombinant proteins were used as antigens
      in Western blot (WB) assays to detect the 229E-specific IgG antibodies and the
      results were compared with a standard serological method, indirect
      immunofluorescence. Serum samples of 51 paediatric patients, suffering from acute
      respiratory illness, and 10 adults, voluntarily infected with human coronavirus,
      were tested. The serum samples of the adult group had coronavirus-specific IgG
      antibodies in both test systems. In contrast, only 8/51 sera of the paediatric
      group were positive for coronavirus-specific IgG by both WB and IF and 20/51 sera
      were positive by WB, but not by IF. The overall incidence of human coronavirus
      infections in the paediatric age group was 55% evaluated by WB analysis and 16%
      evaluated by IF. This study shows that recombinant human coronavirus 229E
      proteins are suitable reagents for the epidemiological screening of coronavirus
      229E infections.

PMID- 8537457
TI  - DNA probe hybridisation in microwells using a new bioluminescent system for the
      detection of PCR-amplified HIV-1 proviral DNA.
AB  - A new bioluminescent detection system combined with a sandwich DNA hybridisation
      reaction in microwells has been developed for the detection of human
      immunodeficiency virus type 1 (HIV-1) provirus DNA amplified by the polymerase
      chain reaction (PCR). First, a fragment of the HIV-1 gag gene was amplified. The
      amplified DNA fragments were denatured and hybridised to a capture probe
      immobilised in microwells and to a biotinylated detection probe. A streptavidin
      pyruvate kinase conjugate could then react on the biotinylated probe and the
      kinase activity detected by means of the luciferin-luciferase system, with
      production of a bioluminescent signal. This sandwich assay followed by a
      bioluminescent reaction detected as little as 7 amol of target DNA. The
      bioluminescent assay detected 5 HIV copies generated after one round of PCR, even
      if no band was seen on an agarose gel. The assay was applied to the detection of
      HIV-proviral DNA in peripheral blood mononuclear cells after one round of PCR and
      allowed to clearly identify a positive sample as compared to nested PCR.

PMID- 8537458
TI  - Titration of human-bovine rotavirus reassortants using a tetrazolium-based
      colorimetric end-point dilution assay.
AB  - A colorimetric end-point dilution assay was developed for the titration of
      rotavirus-containing samples that uses commercially available tetrazolium dyes as
      an indicator of virus infection. This assay offers several advantages over both
      plaque assays and traditional end-point dilution methods. The latter assays
      require manual counting of plaques or the scoring of wells for the presence of
      virus based on observed cytopathic effects. The colorimetric end-point dilution
      assay enables the scoring of wells based upon absorbance readings alone, thereby
      eliminating time-consuming and subjective manual screenings. This method also has
      the potential for automating the analysis of large numbers of samples. Virus
      titers of human-bovine rotavirus reassortants obtained using this method are
      comparable to those determined by plaque assay. The scoring of wells based on
      absorbance readings was also found to agree with manual scoring of cytopathic
      effects and with the production of viral antigen.

PMID- 8537459
TI  - Rapid and sensitive detection of the bovine viral diarrhea virus genome in semen.
AB  - A reverse transcription-polymerase chain reaction (RT-PCR) procedure was
      developed for the detection of bovine viral diarrhea virus (BVDV) in cell culture
      supernatant and in bovine semen. Several sets of primers, PCR conditions and
      extraction methods were examined to optimize the procedure. A set of primers
      designed to amplify a highly conserved portion of the p80 gene from BVDV
      (corresponding to NADL strain sequence from bp 6668 to 7107), was demonstrated to
      be the most effective. These oligonucleotide primers consistently amplify a 440
      bp fragment from several non-cytopathic and cytopathic biotypes of BVDV. The
      viral origin of the PCR products was assessed by sequencing. The introduction of
      a Sephacryl S-400 chromatography step to remove seminal inhibitors prior to RNA
      extraction permitted RT-PCR detection of BVDV in raw and extended semen samples.
      A maximum sensitivity of 0.4 TCID50 was achieved with this method using RNA
      extracted from tissue supernatants. This RT-PCR assay may be a useful tool for
      the detection of BVDV in semen of persistently infected bulls.

PMID- 8537460
TI  - Epitope mapping of the NS4 and NS5 gene products of hepatitis C virus and the use
      of a chimeric NS4-NS5 synthetic peptide for serodiagnosis.
AB  - Specific domains of the NS4 and NS5 gene products of hepatitis C virus have been
      identified using hydrophilicity profiles for the prediction of potential
      immunogenic regions, and epitope scanning techniques. Peptides synthesised on the
      basis of such data show excellent reactivity in the ELISA format. Introduction of
      a glycine-glycine spacer between two peptides (NS4-12 and NS5-44) to give a
      single chimeric peptides does not appear to impair immunoreactivity. An ELISA
      based on the chimeric peptide and a Core-NS3 recombinant protein correctly
      diagnoses a cohort of haemodialysed patients, three commercial HCV panels and the
      sera of a negative control population.

PMID- 8537461
TI  - High efficiency induction of papillomas in vivo using recombinant cottontail
      rabbit papillomavirus DNA.
AB  - Plasmids containing cottontail rabbit papillomavirus (CRPV) DNA can induce
      papillomas in vivo, but efficiency has been low. The aim of the present
      investigation was to explore some of the technical variables involved in
      inoculation of rabbits with recombinant CRPV DNA in attempts to improve both
      yield and consistency of papilloma induction. It was found that induction of
      epidermal hyperplasia, with either a mixture of turpentine and acetone or phorbol
      esters, produced a marked increase in papilloma yield. An additional powerful
      factor was the use of very vigorous, cutaneous scarification, sufficient to
      penetrate the papillary dermis and produce bleeding. When used in combination,
      papilloma yields were consistent and often reached 90-100% of inoculated sites. A
      number of other variables which did not consistently affect papilloma yield were
      tested. These included bleb and puncture injections, plasmid dose, vector type,
      occlusive dressings, lipofection reagent, carrier DNA, and different methods for
      plasmid DNA extraction and purification. It is concluded that the most important
      variables in improving papilloma yields were prior induction of epidermal
      hyperplasia and vigorous cutaneous scarification.

PMID- 8537463
TI  - Determination of the concentration of influenza virus antihaemagglutinin antibody
      molecules of the IgG class and of the equilibrium constant by use of enzyme
      immunoassay titres determined for graded epitope concentrations.
AB  - A new technique for determining the concentration of influenza virus
      antihaemagglutinin antibody molecules of the IgG class (A) and of the equilibrium
      constant K of paratope-epitope interaction is described. The method is based on
      determining enzyme immunoassay (EIA) titres of antibody with graded epitope
      concentrations: EIA titres were defined in terms of the antibody dilution
      yielding a fixed amount of antibody adsorbed per ml (= 6.21 x 10(10)). Adsorption
      of antibody depends on the concentration of paratopes and epitopes allowed to
      react and on the equilibrium constant. For the use of a constant concentration of
      epitopes, the paratope concentration needed to yield the desired degree of
      antibody adsorption decreases with increasing avidity. Therefore, the EIA titres
      increase both with increasing avidity and increasing antibody concentration. When
      graded epitope concentrations are used for determining the EIA titres of a given
      serum, the titres are influenced in a similar manner by the antibody
      concentration of the serum and the increase of titres with increasing epitope
      concentration reflects avidity. The equilibrium constant found is subsequently
      used to determine the concentration of free antibody at the dilution meeting the
      definition of EIA titre and the product of EIA titre and the sum of free and
      bound antibody at this dilution gives the number of antibody molecules present in
      the test serum. A panel of 118 antisera was tested comparatively for A and K
      using the new method and by means of the guanidine titre ratio test and
      equilibrium filtration. The values obtained agreed well with each other. This
      novel technique offers the advantage that it can be easily adapted for use with
      other viruses.

PMID- 8537462
TI  - Simultaneous polymerase chain reaction detection and restriction typing for the
      diagnosis of human genital papillomavirus infection.
AB  - A polymerase chain reaction method has been developed which allows the
      simultaneous detection of the majority of clinically relevant HPV types.
      Degenerate HPV-specific primers direct the one-step amplification of a DNA region
      spanning E1 and E7 genes. This enables an immediate distinction between the two
      groups of papillomaviruses, characterized by high or low oncogenic potential,
      simply from the size of amplified DNA. The PCR product can be subjected to a
      second round of amplification with internal primers, which are specific for 7
      high-risk HPV types, HPV-16, -18, -31, -33, -35, -45 and -58. Precise
      identification of one-step or two-step amplified DNA is done by endonuclease
      digestion with one or two enzymes. The detection sensitivity, which has been
      assessed using cloned HPV genomes and HeLa and CaSki cell lines, varies from a
      few tens to a few hundreds of viral genome equivalents. The accuracy of the
      method has been confirmed by examining cervical scrapings of 44 patients.

PMID- 8537464
TI  - Improvement of African swine fever virus neutralization assay using recombinant
      viruses expressing chromogenic marker genes.
AB  - Antibody neutralization of African swine fever (ASF) virus measured by a plaque
      reduction assay presents frequent difficulties because of the absence or delay in
      plaque formation by many strains, especially low-passage viruses. To overcome
      this problem, a new ASF virus neutralization test has been developed. The new
      test consists of a conventional plaque reduction assay in which the viral plaques
      are detected by expression of marker genes. For the development of this
      neutralization assay 4 mutant viruses were generated by homologous recombination,
      containing beta-galactosidase or beta-glucuronidase reporter genes inserted into
      the thymidine kinase locus of the viral genome. These recombinant viruses have
      the following advantages with respect to parental viruses: (1) the neutralization
      assay takes less than a third of the time needed using non-recombinant viruses;
      (2) the small plaques can be detected more accurately by color contrast; and (3)
      the neutralization-resistant virus clones can be recovered easily post-plaque
      counting. Additionally, these recombinant viruses permit differentiation by
      chromogenic staining of individual infected pig macrophages, the natural host
      cell for ASF virus, facilitating neutralization assays in these primary cultures
      as described in cell lines.

PMID- 8537465
TI  - Sequence identification of antigenic variants in plaque isolates of foot-and
      mouth disease virus.
AB  - Foot-and-mouth disease virus isolates frequently contain mixtures of antigenic
      variants. Using synthetic mixtures of two 'pure' viruses which differed at one
      amino acid of the major epitope, it was found that a minor component present as
      10% or less of the mixture would be undetected by nucleic acid sequencing.

PMID- 8537467
TI  - Anti-CD3-induced changes in protein kinase C isozymes expression in human CD4+
      and CD8+ T lymphocytes.
AB  - In order to determine whether there is a differential expression and activation
      of PKC isozymes between CD4+ and CD8+ T cells, peripheral blood mononuclear cells
      were stimulated with anti-CD3 monoclonal antibody (moAb) for various time
      intervals and the expression of calcium-dependent PKC isozymes (alpha, beta,
      gamma) and calcium-independent PKC isozymes (delta, epsilon, zeta) was analyzed
      with dual color flow cytometry, using anti-PKC isozyme antibodies and anti-CD4 or
      anti-CD8 antibodies. The basal fluorescence intensity of all PKC isozymes was
      comparable between CD4+ T cells and CD8+ T cells. Following activation with anti
      CD3 moAb a marked increase in the fluorescence intensity of all PKC isozymes in
      both CD4+ and CD8+ T cells, albeit to a different extent and with different
      kinetics was observed. Among all PKC isozymes studied, the least striking changes
      were observed in PKC zeta isozyme and the most striking changes were observed in
      PKC-epsilon isozyme. Laser-based confocal microscopic studies confirmed that the
      increase in fluorescence intensity of PKC isozymes following anti-CD3 moAb
      stimulation, as measured by flow cytometry was accompanied by the translocation
      of PKC isozymes from cytosol to the plasma membrane. This study demonstrates a
      differential effect of anti-CD3 moAb on the expression of PKC isozymes between
      CD4+ and CD8+ T cells and suggests that flow cytometry can be used to study the
      translocation of PKC isozymes from cytosol to the plasma membrane.

PMID- 8537468
TI  - TRH receptor on immune cells: in vitro and in vivo stimulation of human
      lymphocyte and rat splenocyte DNA synthesis by TRH.
AB  - This work examined whether (1) immune cells express thyrotrophin releasing
      hormone (TRH) receptor mRNA and (2) TRH modulates lymphocyte activation. By
      Northern blot of RNA extracted from human peripheral blood mononuclear cells
      (PBMC) and rat splenocytes, a single TRH receptor mRNA band of about 3.8 kb
      (identical to that obtained from pituitary cells) was obtained, under both basal
      and stimulated conditions. A significant increase in DNA synthesis was observed
      in phytohemagglutinin-stimulated PBMC and concanavalin A (Con A) stimulated
      splenocytes when TRH (10(-6) M-10(-12) M) was added. After 5, 30, 60, 180 min and
      24 h of TRH administration in vivo, a significant increase in the rat splenocyte
      proliferative response to Con A was observed. In vivo administration of anti-rat
      TSH antibody (1/1000) blocked the increase observed after 30 min of TRH
      administration on the Con A stimulated splenocyte response. TRH possess
      immunostimulatory functions directly via its receptor and indirectly via release
      of other immunostimulatory factors such as thyrotrophin.

PMID- 8537466
TI  - Role of apoptosis in HIV disease pathogenesis.
AB  - After approximately one and a half decades of intensive studies, the exact
      mechanisms to explain HIV-mediated cytopathicity are still enigmatic and need
      closer scrutiny. There has been a dichotomy between virological and immunological
      viewpoints in understanding HIV-mediated cytopathicity, the former emphasizing a
      killing of infected cells by HIV-1 and the latter emphasizing indirect mechanisms
      wherein HIV or its soluble component(s) alter CD4 T-cell function and induce
      susceptibility to apoptosis. Accumulating evidence points to the notion that
      apoptosis might be a major contributor to the depletion of CD4 T-cells in HIV
      infection. This review summarizes current information about the regulatory
      mechanisms of T-cell apoptosis and the role of apoptosis in HIV pathogenesis with
      the goal of providing an integrated view of HIV cytopathicity.

PMID- 8537469
TI  - Rheumatoid factor avidity in patients with rheumatoid arthritis: identification
      of pathogenic RFs which correlate with disease parameters and with the gal(0)
      glycoform of IgG.
AB  - The standard ELISA for measuring rheumatoid factor (RF) binding was modified by
      treatment after the RF-Fc interaction with 2 M guanidine, which allowed a
      measurement of the avidity of the interaction. Incubation with 4 M guanidine
      eliminated RF binding. There was a direct correlation (r = 0.99) between the
      avidity as measured by the modified guanidine ELISA, and the dissociation
      constant for monoclonal RFs, as measured by competitive ELISA. Of the
      seropositive rheumatoid arthritis (RA) patients tested, 47% had high-avidity RFs
      (> or = 8% RF binding remaining after guanidine treatment). Tender joint count
      scores were significantly higher in the high avidity group (p = 0.05), whereas
      there was no significant difference in the ages, disease duration, sedimentation
      rate, RF titer or serum Ig levels compared to those with low-avidity RFs.
      Additionally 58% of those with high-avidity RFs had subcutaneous nodules,
      compared to 40% of the low-avidity group. A significantly higher number of
      nodules was present in the high-avidity RF group compared to those with low
      avidity RFs (p = 0.03). Interestingly, the RF avidity was significantly higher in
      isolated immune complexes (IC), compared to that in circulating IgM RFs (p =
      0.01). The RF avidity correlated with the presence of the glycoform of IgG
      lacking galactose in both circulating and IC-derived IgG (p = 0.003 and 0.009
      respectively). Information about the strength of binding to Fc identifies a
      subgroup of IgM RFs that are likely pathological in patients with RA, as well as
      a specific glycoform of the target antigen.

PMID- 8537470
TI  - Accumulation of donor-specific cytotoxic T cells in intestinal lymphoid tissues
      following intestinal transplantation.
AB  - Utilizing a rat model of semiallogeneic intestinal transplantation, recipients
      were evaluated for accumulation of donor-specific cytotoxic T cells in spleen,
      mesenteric lymph nodes, Peyer's patches, lamina propria, and intraepithelial
      lymphocytes using limiting dilution analysis. Naive animals exhibited a low
      frequency of cytotoxic T cells in spleen and mesenteric lymph nodes with minimal
      activity detected in Peyer's patches and intraepithelial lymphocytes, but not
      detectable activity in lamina propria. Orthotopic intestinal transplantation
      resulted in significant increases in cytotoxic T-cell activity in recipient
      Peyer's patches as early as Day 6 and by Day 8 in spleen, mesenteric lymph nodes,
      lamina propria and intraepithelial lymphocyte populations. Graft lamina propria
      and intraepithelial lymphocytes exhibited significant cytotoxic T-cell activity
      as early as 4 days following transplant. The highest donor-specific cytotoxic T
      cell activity was observed in graft intraepithelial lymphocytes on Day 8
      posttransplant. These studies demonstrate rapid expansion of donor-specific
      cytotoxic T cells which migrate to the graft site within 4 days after
      semiallogeneic intestinal transplantation.

PMID- 8537471
TI  - Clinical and biological significance of interleukin-10 plasma levels in patients
      with septic shock.
AB  - Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits
      lipopolysaccharide-induced tumor necrosis factor production. We determined the
      plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock
      and in 11 patients with circulatory shock of nonseptic origin. In septic shock,
      interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and
      decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma
      levels also increased during the first 24 h but to a lesser extent (median: 17
      pg/ml). In septic shock patients, interleukin-10 plasma levels were positively
      correlated with tumor necrosis factor (r = 0.8, p = 0.01) and with parameters of
      shock severity including lactate levels (r = 0.56, p < 0.05) and correlated
      negatively with blood platelet counts (r = -0.65, p < 0.05). The decreased
      production of tumor necrosis factor-alpha and interleukin-6 after in vitro
      incubation of whole blood from septic shock patients with lipopolysaccharide was
      not influenced by in vitro neutralization of interleukin-10. We conclude that
      interleukin-10 is produced in patients with circulatory shock of septic and
      nonseptic origin and that the production of this anti-inflammatory cytokine
      during septic shock correlates positively with the intensity of the inflammatory
      response.

PMID- 8537472
TI  - Increased uterine and ovarian vascular resistance following Filshie clip
      sterilization: preliminary findings obtained with color Doppler ultrasonography.
AB  - The effect of Filshie clip sterilization on uterine and ovarian circulation was
      studied with color Doppler ultrasonography in 16 women before and twice after the
      operation. As a whole, the vascular resistance was slightly raised in the largest
      uterine artery and in the fundal parts of the uterine arteries; likewise in the
      ovarian arteries 2 days after sterilization. The resistance in the uterine
      arteries approached the presterilization level at 3 months after the operation,
      although these changes were not statistically significant. Two women had pelvic
      pain in the first days after the procedure, and they were compared with the
      symptom-free patients. Two days after sterilization, the patients with pain had
      significantly higher vascular resistance in all parts of the uterine arteries as
      compared to the symptom-free patients. After 3 months the difference had
      decreased in the largest uterine arteries and in the middle parts of the uterine
      arteries, but in the fundal parts the resistance was still higher than before
      sterilization. Vascular resistance in the ovarian arteries was increased in both
      groups, although the elevation was more pronounced in patients with pain. These
      preliminary findings imply that sterilization may cause an increase in the local
      vascular resistance, which is measurable by color Doppler sonography.

PMID- 8537473
TI  - Transcranial Doppler ultrasound assessment of intracranial hemodynamics in
      children with diabetic ketoacidosis.
AB  - The pathophysiology of acute neurological complications of diabetic ketoacidosis
      (DKA) in children and adolescents is not completely understood. We sought to
      establish whether transcranial Doppler (TCD) was able to monitor the changes of
      cerebral blood flow regulatory mechanisms, as measured by cerebral blood
      velocities (CBF-V), Gosling's pulsatility index (PI), and cerebral vascular
      reactivity (VR), prior to and during treatment of DKA. The increased values of PI
      suggested an increase of intracranial pressure (ICP) due to the existence of
      cerebral vasoparalysis, based on the low values of VR prior to treatment and 6
      hours after initiation of treatment. At 24 hours, the correction of hematocrit
      and pH was associated with a significant decrease of PI, suggesting a decrease of
      ICP, likely due to a return of vascular tone in response to the low PaCO2. This
      was further supported by an increase of VR in all patients. At 48 hours, when
      PaCO2 returned to normal, the PI remained low and the VR increased further,
      suggesting a complete reversal of vasoparalysis and a return of cerebral blood
      flow regulatory mechanisms.

PMID- 8537474
TI  - Early fetal circulation in pregnancies complicated by retroplacental hematoma.
AB  - The objective of this study was to investigate the effects in early gestation of
      retroplacental hematomas on Doppler indices measured in different fetal vascular
      districts and to relate these changes, if any, to the volume of hematoma and
      pregnancy outcome. Thirty-eight pregnancies complicated by bleeding and
      ultrasonographic findings of retroplacental hematomas were considered for this
      study. Menstrual age ranged between 9 and 14 weeks. Blood flow velocity waveforms
      were measured in the umbilical artery, descending aorta, middle cerebral artery,
      and inferior vena cava. The pulsatility index in arterial vessels was calculated
      as well as the percentage reverse flow in the inferior vena cava. The values
      obtained were compared to previously constructed reference limits. No significant
      differences were found for any of the Doppler indices when the values obtained in
      pregnancies complicated by retroplacental hematomas were compared to the
      reference limits. Furthermore no significant relationships were found between the
      Doppler indices and either the size of hematoma or pregnancy outcome. In
      conclusion, retroplacental hematoma does not induce hemodynamic effects in the
      fetal circulation before 14 weeks, menstrual age. These data do not support the
      use of Doppler ultrasonography in early gestation for pregnancies complicated by
      bleeding and retroplacental hematomas.

PMID- 8537475
TI  - Ultrasound-guided fine-needle aspiration biopsy of solitary pulmonary nodules.
AB  - Ultrasound-guided fine-needle aspiration biopsy (US-guided FNAB) was performed in
      40 patients with solitary pulmonary nodules (SPNs) for evaluation of diagnostic
      results and complication rates. The final diagnoses of the 40 patients included
      30 malignancies and 10 benign lesions. Using US-guided FNAB, the diagnostic
      yields were 97% (29/30) in malignancies and 60% (6/10) in benign lesions. Of the
      29 patients with cytologically proven malignancies, 12 underwent surgical
      resection. The correlation between cytological results and histologic diagnoses
      in these 12 was excellent (100%). The size of the nodule did not affect the
      diagnostic rate or complication rate. Only two patients (5%) developed minimal
      pneumothorax after US-guided FNAB. We conclude that US-guided FNAB is a useful,
      safe, and convenient diagnostic tool for SPN, and that malignant pulmonary
      nodules are more easily diagnosed than benign nodules.

PMID- 8537476
TI  - Quantitative characterization of color Doppler images: reproducibility, accuracy,
      and limitations.
AB  - A computer-based quantitative analysis for color Doppler images of complex
      vascular formations is presented. The red-green-blue-signal from an Acuson XP10
      is frame-grabbed and digitized. By matching each image pixel with the color bar,
      color pixels are identified and assigned to the corresponding flow velocity
      (color value). Data analysis consists of delineation of a region of interest and
      calculation of the relative number of color pixels in this region (color pixel
      density) as well as the mean color value. The mean color value was compared to
      flow velocities in a flow phantom. The thyroid and carotid artery in a volunteer
      were repeatedly examined by a single examiner to assess intra-observer
      variability. The thyroids in five healthy controls were examined by three
      experienced physicians to assess the extent of inter-observer variability and
      observer bias. The correlation between the mean color value and flow velocity
      ranged from 0.94 to 0.96 for a range of velocities determined by pulse repetition
      frequency. The average deviation of the mean color value from the flow velocity
      was 22% to 41%, depending on the selected pulse repetition frequency (range of
      deviations, -46% to +66%). Flow velocity was underestimated with inadequately low
      pulse repetition frequency, or inadequately high reject threshold. An
      overestimation occurred with inadequately high pulse repetition frequency. The
      highest intra-observer variability was 22% (relative standard deviation) for the
      color pixel density, and 9.1% for the mean color value. The inter-observer
      variation was approximately 30% for the color pixel density, and 20% for the mean
      color value. In conclusion, computer assisted image analysis permits an objective
      description of color Doppler images. However, the user must be aware that image
      acquisition under in vivo conditions as well as physical and instrumental factors
      may considerably influence the results.

PMID- 8537477
TI  - Assessment of fetal breathing movements using three different ultrasound
      modalities.
AB  - Twenty-five consecutive women in the third trimester of pregnancy were studied to
      determine the presence or absence of fetal breathing movements using three
      different ultrasound imaging techniques. Using real-time B-mode observation of
      the fetal trunk as the standard, image-directed pulsed wave Doppler insonation of
      the umbilical vein confirmed the presence of breathing movements with a
      sensitivity of 100% and the absence of breathing movements with a specificity of
      100%. The sensitivity and specificity of color Doppler imaging of the fetal naso-
      and oropharynx for the presence or absence of fetal breathing movements were 96%
      and 100%, respectively. In the current study, the detection of fetal breathing
      movements by three different ultrasound modalities was virtually interchangeable.

PMID- 8537478
TI  - Prenatal diagnosis of mucoid degeneration of the umbilical cord.

PMID- 8537479
TI  - Duplication of gallbladder associated with cholelithiasis: sonographic detection.

PMID- 8537480
TI  - A prune-induced small intestinal obstruction: sonographic appearance.

PMID- 8537481
TI  - Ultrasonographic findings in scrotal filarial elephantiasis.

PMID- 8537482
TI  - Testing healthcare staff for infection with HIV and hepatitis: logistic and
      ethical considerations.

PMID- 8537484
TI  - Parathyroid hormone related protein and interleukin-6 mRNA expression in larynx
      and renal cell carcinomas from normocalcaemic and hypercalcaemic patients.
AB  - AIMS: To determine the expression of parathyroid hormone related protein (PTHrP)
      and interleukin-6 (IL-6) mRNAs and their possible relation in malignant tumours,
      derived from patients with and without hypercalcaemia, commonly associated with
      humoral hypercalcaemia of malignancy. METHODS: PTHrP and IL-6 mRNA expression was
      studied by northern blot analysis in tumour specimens from 13 consecutive
      patients. Six patients (two with hypercalcaemia) had squamous cell carcinomas of
      the larynx and seven (one with hypercalcaemia) had renal cell carcinomas.
      RESULTS: There was no relation between the histological features of the tumours
      and the expression of either PTHrP or IL-6 mRNAs. PTHrP mRNA was detected in all
      squamous cell carcinomas, expression being highest in the two patients with
      hypercalcaemia. In the renal cell carcinomas PTHrP mRNA was expressed only in the
      patient with hypercalcaemia. IL-6 mRNA was detected in nearly all tumours studied
      but there was no apparent relation between its expression and that of PTHrP mRNA
      or serum calcium concentrations. CONCLUSIONS: PTHrP mRNA expression is increased
      in patients with hypercalcaemia but is not related to IL-6 mRNA expression. The
      results suggest a quantitative relation between PTHrP gene expression and
      hypercalcaemia, and imply that different mechanisms account for this expression
      in squamous and renal cell carcinomas.

PMID- 8537485
TI  - An easier alternative to orthogonal regression for calculation of International
      Sensitivity Indexes.
AB  - AIMS: To evaluate an easier alternative method to orthogonal regression analysis
      for calculating International Sensitivity Indexes (ISI). METHODS: ISI for 18
      reagents were estimated from reference and test reagent prothrombin times using
      plasma from 60 stabilised patients undergoing anticoagulation therapy and 20
      normal subjects. ISI were also derived for 12 systems (instrument/reagent
      combination) using lyophilised plasma calibrants. Orthogonal regression and the
      easier alternative log ratio method were evaluated by comparing resultant
      International Normalised Ratios (INR) for 58 patients using two test systems.
      RESULTS: For the reagent calibrations, the differences in the two methods for the
      sensitivity slopes were very small. For the system calibrations, slope
      differences were still of little clinical importance. Parallel observations for
      INR on the 58 patients confirmed that the bias introduced by easier log ratio
      derivation of ISI was small and of minor clinical importance, although the bias
      increases for high INR. CONCLUSIONS: The easier method for ISI determination is a
      useful alternative to orthogonal regression analysis, particularly when computer
      assistance is not available, for checking for gross errors in computer
      computation and for use when calculating ISI from INR calibrants.

PMID- 8537483
TI  - Steroid hormone receptors and their clinical significance in cancer.

PMID- 8537486
TI  - Use of dried blood spots for the detection and confirmation of HTLV-I specific
      antibodies for epidemiological purposes.
AB  - AIMS--To modify and evaluate a gelatin particle agglutination test that could
      provide a sensitive, specific and inexpensive method for the detection of HTLV-I
      antibody in dried blood spot samples (DBS) collected on filter paper. METHODS--A
      set of 26 reference samples confirmed as HTLV-I antibody positive were assembled
      from patients with tropical spastic paraparesis or adult T cell leukaemia and
      blood donors. Serum samples and simulated antibody positive dried blood spot
      eluates were tested using the Serodia assay together with two confirmatory tests:
      HTLV BLOT 2.3, a western blot, and Select-HTLV, an enzyme immunoassay (EIA). Both
      confirmatory tests use synthetic peptides to differentiate between antibodies to
      HTLV-I and -II. The modified Serodia assay was then used to test anonymously
      10,135 DBS collected from neonates from London. Samples reactive in the modified
      Serodia test producing a positive result were titrated to an end point and
      confirmed as before. RESULTS--All 26 eluates made from simulated DBS derived from
      positive reference samples were identified as positive by the modified Serodia
      HTLV-I test and were confirmed as anti-HTLV-I positive by EIA. Two eluates
      derived from relatively low titre reference samples gave indeterminate results on
      western blotting. Screening of the 10,135 neonatal DBS resulted in six repeat
      reactives, five of which were confirmed. The remaining reactive sample gave an
      indeterminate result on western blotting and there was insufficient eluate for
      testing by EIA. The overall seroprevalence of HTLV-I in this population was 0.05%
      (five of 10,135). CONCLUSION--The modified Serodia HTLV-I assay provides a
      sensitive, specific and inexpensive (10 pence/test) method for screening large
      numbers of DBS. The format of the assay makes it ideally suited for simultaneous
      screening of antibodies to HIV-1, HIV-2 and HTLV-I using semi-automated
      equipment.

PMID- 8537487
TI  - Serological reactivity against cyst and tachyzoite antigens of Toxoplasma gondii
      determined by FAST-ELISA.
AB  - AIMS: To obtain quantitative data on the human serological response to Toxoplasma
      gondii tachyzoite and bradyzoite antigens. METHODS: Serum samples from 30
      patients who had positive antibody titres against T gondii and from 14 who were
      seronegative, together with sequential serum samples from four infected
      individuals, were screened by FAST-ELISA. RESULTS: Serum samples from the 30
      seropositive patients showed high IgG and IgM titres against the T gondii
      tachyzoite antigen but very low responses to cyst antigen. This result was borne
      out in sequential serum samples from patients with toxoplasmosis. CONCLUSION:
      Antibody recognition of the cystic stage of T gondii is low, implying that either
      this stage is poorly immunogenic or that the antigen load is low.

PMID- 8537488
TI  - Detection of bacteraemia by the continuously monitoring BacT/Alert system.
AB  - AIMS: To analyse a continuously monitoring blood culture system with respect to
      the time to detection of various groups of organisms, their clinical importance,
      and the relative efficacy of the aerobic and anaerobic bottles. METHODS: Four
      thousand blood cultures were monitored and the information relating to the
      positive cultures was noted and analysed. RESULTS: Four hundred and seventy seven
      blood cultures were detected as positive, 81% (387/477) of which were detected
      within 48 hours. The most pathogenic organisms were detected in the shortest
      period, less pathogenic later and those generally regarded as contaminants last.
      Clinically important isolates were also detected earlier. Many positive blood
      cultures were detected in only one bottle of the set, even those regarded as
      clinically important. CONCLUSIONS: The management of continuously monitoring
      blood culture systems could be improved by considering time to detection trends.
      Clinicians should be aware of the relatively rapid detection of clinically
      important, positive blood cultures in relation to patient treatment.

PMID- 8537489
TI  - Perceptions of a medical microbiology service: a survey of laboratory users.
AB  - AIM: To ascertain the perception of laboratory users regarding the quality of the
      medical microbiology services in a district general hospital. METHODS: Detailed
      questionnaires were circulated to all clinicians in the locality, with headings
      covering the quality of medical advice provided, the availability of information
      on specimen collection, format of request forms, specimen transport arrangements,
      turnaround times, the quality and need for interpretative advice, and the overall
      impression of the quality of the services provided. RESULTS: Two hundred and
      thirty five replies were received, giving a response rate of 69%. Transportation
      of specimens and communication of reports were identified as priority areas for
      improvement. The overall quality of the service was perceived as satisfactory,
      although areas were identified where substantial improvements could be made, some
      at little or no cost to the laboratory. CONCLUSIONS: The survey focused
      clinicians' attention on the service, raised the profile of the laboratory, and
      resulted in improved communications and a better understanding of customer needs.
      Overall, the exercise was felt to be extremely useful, and worthwhile repeating
      to gauge the effect of the changes instituted as a result.

PMID- 8537490
TI  - Comparison of three methods for culture confirmation of Neisseria gonorrhoeae
      strains currently circulating in the UK.
AB  - AIMS: To establish the current sensitivity of two commercial kits for culture
      confirmation of Neisseria gonorrhoeae strains circulating in the UK. METHODS: A
      total of 544 strains were studied (199 gonococci from male patients attending
      hospitals in the county of Avon, 204 unselected N gonorrhoeae isolates from male
      patients in Leeds, 20 strains referred to the Gonococcus Reference Unit because
      of difficulties with the Syva fluorescent antibody test (FAT), and 121 strains
      collected over a four year period which had not reacted with serotyping
      antibodies). Strains were tested by sugar utilisation in cysteine trypticase base
      agar (CTA test), the Phadebact Monoclonal GC Test and Syva MicroTrak Neisseria
      gonorrhoeae Culture Confirmation Test. The auxotype and serovar of each strain
      were also determined. RESULTS: The sugar utilisation test confirmed the identity
      of 99% (197/199) of gonococci from Avon and 97% (198/204) of those from Leeds.
      The Syva FAT confirmed 76% (151/199) of isolates from Avon and 84% (171/204) of
      those from Leeds. The Phadebact test confirmed all but one isolate from the 403
      strains from both cities. Half of the 20 referred FAT negative isolates also give
      a negative result in the Syva FAT; however, only 10% of the remainder gave a
      strong reaction in our laboratory. All serotyping antibody negative strains were
      negative in the FAT, although all these and all of the 20 strains that give a
      negative result in the FAT gave positive reactions in the other culture
      confirmation tests. Typing tests revealed a greater diversity amongst the FAT
      negative strains from Leeds than those from Avon. CONCLUSIONS: Considerable
      differences in the sensitivity of the MicroTrak but not with the Phadebact or CTA
      tests were found for the identification of isolates from two geographically
      distinct areas of the UK. Our results suggest that the Syva FAT would not be
      suitable, if used alone, for culture confirmation in Avon or Leeds.

PMID- 8537491
TI  - IS6110 based amplityping assay and RFLP fingerprinting of clinical isolates of
      Mycobacterium tuberculosis.
AB  - AIMS: To evaluate the usefulness of two IS6110 based typing methods, an
      amplityping assay and restriction fragment length polymorphism (RFLP) analysis,
      for fingerprinting respiratory isolates of Mycobacterium tuberculosis. METHODS:
      For amplityping, a pair of primers which amplify the intervening sequence between
      the repetitive insertion sequence IS6110 was used to generate a banding pattern
      which was confirmed by hybridisation. This assay was compared with conventional
      chromosomal DNA RFLP typing in the evaluation of 110 epidemiologically diverse
      isolates. RESULTS: Polymerase chain reaction (PCR) amplityping generated a single
      pattern in Hong Kong Chinese strains, but two and four diverse patterns in
      Filipino and Vietnamese strains, respectively, and could be completed within four
      days. When compared with chromosomal DNA RFLP typing, which took three weeks to
      complete, four different RFLP patterns could be seen among the Chinese strains,
      while seven patterns were found in the Filipino and Vietnamese strains. No change
      in amplityping or RFLP patterns was found in 36 sequential isolates from the same
      patients after anti-tuberculosis treatment for up to 12 months, despite the
      emergence of resistance in three of these strains. No specific amplityping or
      RFLP pattern could be related to different patterns of drug susceptibility.
      CONCLUSION: PCR amplityping could be used initially as a rapid typing method to
      distinguish strains originating from different localities. This could be
      important for investigation of outbreaks of tuberculosis--for example, in refugee
      camps.

PMID- 8537492
TI  - Lethal synergy between toxins of staphylococci and enterobacteria: implications
      for sudden infant death syndrome.
AB  - AIM: To test the hypothesis that lethal synergy occurs between toxin preparations
      of nasopharyngeal staphylococci and enterobacteria from sudden infant death
      syndrome (SIDS) victims and matched healthy infants. METHODS: SIDS and matched
      healthy babies were studied if both staphylococcal and enterobacterial strains
      were isolated from the nasopharynx. The lethality of toxin preparations from each
      bacterial isolate (separately and combined) was assessed over a range of
      dilutions using the chick embryo assay system. RESULTS: Staphylococci and
      enterobacteria were isolated together from the nasopharynx of seven SIDS babies
      but from only one normal healthy infant. Enterobacterial toxins were lethal at
      high dilutions. Staphylococcal toxins were less toxic. Simultaneous testing in
      the chick assay of staphylococcal and enterobacterial toxins, from each baby, at
      non-lethal concentrations enhanced lethality levels by 177 to 1011% compared with
      lethality expected by an additive effect alone. CONCLUSIONS: Synergy occurs
      between the toxins of nasopharyngeal staphylococci and enterobacteria. This
      combination of strains is more likely to occur in the nasopharynx of SIDS victims
      than that of healthy infants.

PMID- 8537493
TI  - Sampling variability of percutaneous liver biopsy in primary sclerosing
      cholangitis.
AB  - AIMS: To study sampling variability of percutaneous liver biopsy in primary
      sclerosing cholangitis (PSC). METHODS: One hundred and twelve biopsy specimens
      (that is, 56 pairs) from 44 patients with PSC, confirmed by cholangiography, were
      evaluated blindly. Six different features, qualitative grading of four other
      features and staging according to Ludwig were assessed. RESULTS: Quantitative
      sampling variability was confined mainly to just one grade or stage, although 11%
      (six of 56) of the biopsy specimen pairs differed by more than one stage (7% (one
      of 15) in pairs > 2 cm in length). Qualitative sampling variabilities were
      between 18 and 71%. Advanced disease (stages 3 or 4) was missed in 40% (two of
      five) of the biopsy specimens while cirrhosis was missed in 37%. CONCLUSION:
      Paired liver biopsy specimens should be taken in clinical studies of PSC using
      liver histology for evaluation or prognosis.

PMID- 8537494
TI  - Prospective audit of mucosal biopsy specimens of the gastrointestinal tract.
AB  - AIMS: To determine why mucosal biopsy specimens of the gastrointestinal tract
      were taken and whether they were justified on clinical or pathological grounds.
      METHODS: A prospective audit of 190 consecutive biopsy specimens received in a
      university hospital histology department over six weeks. RESULTS: The 31 separate
      presenting symptoms included diarrhoea (34%), abdominal pain (16%) and rectal
      bleeding (15%). In 41% (78/190) the histology was normal, 28% (53/190) showed
      inflammatory changes and 11% 21/190) carcinoma. A clear justification for the
      procedure was identified in over 90% (171/190) of patients. In 36% (68/190) there
      was a change in patient management on receipt of biopsy reports and further
      investigations were ordered in 29% (55/190). The mean time taken to report biopsy
      specimens was 4.7 working days and there was no difference between the reporting
      time of a pathologist compared with a consultant or a trainee. CONCLUSIONS: There
      is no evidence that mucosal biopsy specimens are taken unnecessarily.

PMID- 8537495
TI  - Lymphocytic gastritis and associated small bowel disease: a diffuse lymphocytic
      gastroenteropathy?
AB  - AIM: To investigate the natural history of lymphocytic gastritis (LG) and its
      relation to Helicobacter pylori infection and to coeliac disease using serology,
      duodenal biopsy and a small intestinal permeability test. METHOD: Twenty two
      patients diagnosed as having LG between 1984 and 1994 were investigated by upper
      gastrointestinal endoscopy at which gastric and duodenal biopsy specimens were
      taken for histological assessment and immunohistology. Serum was collected for
      measurement of anti-H pylori, anti-gliadin and anti-endomysial antibodies. A
      lactulose/mannitol absorption test was performed within one week of endoscopy.
      Control groups were studied by histology, serology and permeability tests.
      RESULTS: Three patients had been recently diagnosed as having LG while 15 still
      had the condition after a mean of 13.9 (range two to 38) months. LG involved the
      antrum alone in three patients, antrum and body in seven, body alone in six, and
      gastric remnant in two. Gastroduodenal intraepithelial lymphocytes (IELs) were T
      cells and predominantly of T suppressor (CD8) type. Duodenal IELs were increased
      compared to age/sex matched controls with chronic gastritis. Four patients had
      duodenal villous atrophy. Four patients no longer had LG after a mean of 29.3 (10
      70) months but had increased gastroduodenal IELs. H pylori was present in four
      (22%) of 18 patients with LG but H pylori serology was positive in 11 (61%) of
      18. There was no difference in seropositivity when compared with age/sex matched
      controls with dyspepsia. Eleven of 20 patients with LG tested had abnormal
      lactulose/mannitol absorption (v none of 22 controls with chronic gastritis).
      Four patients with LG, all with villous atrophy, were seropositive for IgA
      endomysial antibody. CONCLUSIONS: The persistence of LG with time, the
      association with increased duodenal IELs and abnormal small intestinal
      permeability suggests LG may be a manifestation of a diffuse lymphocytic
      gastroenteropathy related to sensitivity to gluten or some other agent.

PMID- 8537496
TI  - Association of Epstein-Barr virus with sinonasal angiocentric T cell lymphoma.
AB  - AIM: To investigate whether non-Hodgkin's lymphomas arising in the sinonasal
      region or Waldeyer's ring contain the Epstein-Barr virus (EBV) genome in lesional
      tissue. METHOD: Sections from paraffin wax blocks of 22 lymphoid proliferations
      arising in the sinonasal region or Waldeyer's ring were studied with EBV encoded
      RNAs (EBER-1 and -2) using in situ hybridisation. RESULTS: EBV was detected in
      nuclei of tumour cells of five of seven T cell lymphomas and in nuclei of two of
      seven diffuse, large cell immunoblastic lymphomas of B phenotype in the sinonasal
      region. Of tumours arising in Waldeyer's ring, two of 10 non-Hodgkin's lymphomas
      (both large cell) were positive, as was a single case of Hodgkin's disease.
      Lymphoma of other types, including Western type Burkitt's lymphoma, and nodular
      and diffuse small cleaved cell lymphoma, were negative. CONCLUSION: EBV is highly
      associated with large cell lymphomas especially T cell lymphomas of sinonasal
      origin in the indigenous Irish population, underlining the importance of this
      virus in nasopharyngeal lymphomas in Northern European as well as Asian
      populations.

PMID- 8537497
TI  - Immunohistochemical identification of tumours of adipocytic differentiation using
      an antibody to aP2 protein.
AB  - AIM: To determine whether aP2 expression is a useful diagnostic marker in soft
      tissue tumour pathology. METHODS: A polyclonal antibody to aP2 was used to
      investigate the immunohistochemical expression of this protein in benign and
      malignant tumours of adipocytic differentiation and a wide variety of other
      neoplasms. RESULTS: aP2 was only expressed by lipoblasts (in all types of
      liposarcoma and in lipoblastomatosis) and by brown fat cells (in both hibernomas
      and normal periadrenal fetal fat). Other benign adipose tissue tumours and
      malignant connective tissue or epithelial tumours were distinguished from
      liposarcoma by the absence of staining for aP2. CONCLUSION: Identification of
      lipoblasts using markers of aP2 expression is of value in the differential
      diagnosis of benign and malignant adipose tissue tumours and in distinguishing
      liposarcomas from other malignant mesenchymal and epithelial neoplasms, some of
      which contain cells that morphologically resemble lipoblasts.

PMID- 8537498
TI  - Diagnostic relevance of peripheral blood immunocytochemistry in hairy cell
      leukaemia.
AB  - AIMS--(1) To assess the diagnostic relevance of peripheral blood
      immunocytochemistry in hairy cell leukaemia (HCL); (2) to compare the
      immunostaining of bone marrow biopsy specimens with bone marrow and peripheral
      blood cytospins; (3) to evaluate the sensitivity of the different markers used;
      (4) to identify the ultrastructural localisation of DBA.44 in HCL variant.
      METHODS--Immunoenzymatic staining procedures, immunoperoxidase and immunoalkaline
      phosphatase, were used with a panel of monoclonal antibodies directed to HCL
      associated antigens. Ultrastructural immunostaining was performed using colloidal
      gold conjugated antibodies. RESULTS--HCL showed strong cytoplasmic reactivity for
      CD22, CD25, CD103, DBA.44, kappa, or lambda light chains. Peripheral blood
      diagnostic hairy cells were found in all the cases with absolute counts ranging
      from 0.11 x 10(9)/l up to 6.4 x 10(9)/l and values increasing with the size of
      the spleen. A median of 36.5% of leukaemic cells was found in bone marrow
      aspirates and 70% in bone marrow trephine specimens. The monoclonal antibodies
      CD22 and DBA.44 showed the highest and the lowest percentage of positive hairy
      cells, respectively; this difference was statistically significant (p = 0.0025).
      Ultrastructural immunolabelling with DBA.44 showed a cytoplasmic membrane
      localisation of the antigen in one case of HCL variant. CONCLUSIONS--(1)
      Immunocytochemistry is a useful technique which enhances the accuracy of
      diagnosis in HCL; (2) peripheral blood immunocytochemistry is recommended because
      it highlights hairy cells in all cases; (3) CD22 appears to be the most sensitive
      of the markers tested; (4) ultrastructural analysis is a useful tool in selected
      cases of HCL variant.

PMID- 8537499
TI  - Hypercalcaemia due to calcium binding IgM paraprotein in Waldenstrom's
      macroglobulinaemia.
AB  - A case of Waldenstrom's macroglobulinaemia with asymptomatic hypercalcaemia is
      reported in which calcium binding to the paraprotein was found. This is the first
      report of this phenomenon in Waldenstrom's macroglobulinaemia and the first
      report of calcium binding to an IgM paraprotein.

PMID- 8537500
TI  - Langerhans' cell histiocytosis: possible association with malignant germ cell
      tumour.
AB  - A rare case of adult onset Langerhans' cell histiocytosis associated with
      dysgerminoma in a 35 year old Chinese woman is reported. The patient had a
      history of dysgerminoma of left ovary 15 years previously and had undergone
      surgery followed by radiotherapy and an uneventful recovery. She presented again
      in March 1994, this time with a left clavicular mass, which was shown
      histologically to be Langerhans' cell histiocytosis. The report illustrates the
      probable association between the two lesions, with some discussion on the
      underlying pathogenesis.

PMID- 8537501
TI  - Papillary mucinous adenoma arising in adenomyomatous hyperplasia of the gall
      bladder.
AB  - A case of papillary mucinous adenoma arising in adenomyomatous hyperplasia (AMH)
      of the gall bladder is reported. The lesion was unsuspected and discovered by
      routine palpation of the gall bladder during laparotomy. The adenoma developed
      within fundal AMH and showed cytological atypia. This case illustrates that
      neoplastic proliferation is indeed possible in AMH and challenges the classical
      opinion that AMH is devoid of neoplastic potential.

PMID- 8537502
TI  - Induction of interleukin-8 secretion from gastric epithelial cells by a cagA
      negative isogenic mutant of Helicobacter pylori.
AB  - The ability of Helicobacter pylori strains to induce interleukin-8 (IL-8) gene
      expression and protein secretion from gastric epithelial cell lines in vitro is
      variable. This cellular response is associated with bacterial expression of the
      CagA protein present in type I H pylori strains. To determine the role of CagA in
      this host cell response, an isogenic cagA negative mutant, N6.XA3, was
      constructed. The cagA negative isogenic mutant and the wild-type parental cagA
      positive strain, N6, were cocultured with AGS, ST-42 and KATO-3 gastric
      epithelial cell lines and secreted interleukin-8 assayed by enzyme linked
      immunosorbent assay. In all three cell lines there was no significant difference
      in the IL-8 secretion induced by the cagA negative isogenic mutant, N6.XA3, and
      the wild-type parent strain, N6. These studies show that CagA is not the inducer
      of IL-8 secretion from gastric epithelial cells. As all wild-type CagA positive
      strains studied to date induce IL-8, the bacterial factor(s) inducing this
      inflammatory response is closely associated with the expression of CagA.

PMID- 8537503
TI  - A practical single sample dry latex agglutination test for Helicobacter pylori
      antibody detection.
AB  - Assessment of a single serum sample for Helicobacter pylori antibodies is
      frequently requested in routine diagnostic laboratories. Current enzyme linked
      immunosorbent assay (ELISA) kits are not ideal for testing small numbers of serum
      samples and some have low sensitivities, specificities or large grey zones. A
      panel of 90 serum samples from patients who had presented for routine upper
      endoscopy was used to compare three kits for the detection of H pylori
      antibodies: (1) Pyloriset Dry, total antibody latex agglutination, Orion
      Diagnostica, Espoo, Finland; (2) Pyloriset enzyme immunoassay (EIA), IgG ELISA,
      Orion; and (3) Hel-p, IgG ELISA, Amrad, Kew, Victoria, Australia. Diagnosis of H
      pylori positivity was made if culture results and either rapid urease test or
      histopathology were positive. The sensitivity, specificity, positive, and
      negative predictive value for each test was as follows: Orion: latex 93.3%,
      95.6%, 95.5%, 93.3%, respectively; Orion: EIA-G 84.4%, 97.8%, 97.4%, 84.4%,
      respectively; and Amrad: EIA-G 100%, 88.9%, 90%, 100%, respectively. The latex
      test performed better than the EIAs with respect to sensitivity and specificity.

PMID- 8537504
TI  - Corynebacterium aquaticum septicaemia in a neutropenic patient.
AB  - Corynebacteria are a well recognised cause of sepsis in the immunocompromised
      patient. Corynebacterium aquaticum, however, is rarely seen in the clinical
      setting, being an environmental organism associated with fresh water. A
      septicaemic episode caused by this organism in a 74 year old neutropenic woman
      with an indwelling central venous catheter is reported. It is postulated that the
      source of the organism was untreated stored rainwater which she used for
      showering.

PMID- 8537505
TI  - Transient abnormal myelopoiesis accompanied by hepatic fibrosis in two infants
      with Down syndrome.
AB  - Two necropsy cases of Down syndrome are reported. These showed transient abnormal
      myelopoiesis accompanying characteristic hepatic sinusoidal fibrosis. Numerous
      megakaryocytes were found in the liver of one case, but not in the other. Only
      eight cases of Down syndrome with simultaneous occurrence of hepatic fibrosis and
      transient abnormal myelopoiesis have been reported. The cases described here
      showed slight fibrotic changes in the hyperplastic bone marrow, which were not
      found in the previously reported cases of transient abnormal myelopoiesis.

PMID- 8537506
TI  - Acute hepatic and renal failure caused by Pneumocystis carinii in patients with
      AIDS.
AB  - Clinical and pathological findings are described in two AIDS patients with
      Pneumocystis carinii infection who received prophylactic treatment with nebulised
      pentamidine and developed unusual hepatic and renal failure. Histological
      examination showed clumps of P carinii massively obstructing hepatic sinuses and
      portal vessels in the first patient, and merular and intertubular capillaries in
      the second. These findings could explain the unusual clinical features,
      characterised by acute hepatic and renal failure.

PMID- 8537507
TI  - Origins of breath isoprene.

PMID- 8537508
TI  - MR and CT appearance of urethral clear cell adenocarcinoma in a woman.
AB  - We present a case of clear cell adenocarcinoma of the female urethra that has
      been evaluated with CT and MRI. The lesion was a well-demarcated mass surrounded
      with peripheral enhancement on CT. On MRI a sharply marginated mass was located
      in the midurethra, giving rise to a smooth elevation of the bladder base. On T2
      weighted imaging, the lesion was hyperintense, being surrounded by a ring of
      lower signal intensity at the periphery. A central urethral dot of lower signal
      intensity traversed the anterior one-third of the mass but was preserved in its
      entire length.

PMID- 8537509
TI  - Multiple brain abscesses in chain and cluster: CT appearance.

PMID- 8537510
TI  - CT and MRI of intracavernous carotid artery aneurysm with occlusion of the
      cervical internal carotid artery.

PMID- 8537511
TI  - Postcontrast dural MR enhancement and acute CSF intracranial hypotension.

PMID- 8537512
TI  - MRI of cavum vergae without cavum septi pellucidi.

PMID- 8537513
TI  - True sagittal CT scanning of the elbow.
AB  - OBJECTIVE: A new method to obtain true sagittal CT scans of the elbow joint is
      described. MATERIALS AND METHODS: The patient is placed prone on the CT table
      with the arm around and under the table. RESULTS: True sagittal images of the
      elbow joints and all the articulating surfaces were easily obtained in a standard
      and reproducible manner. CONCLUSION: For CT scanning of the elbow, true sagittal
      scanning is superior to axial views and is readily obtained by the described
      method.

PMID- 8537514
TI  - Echo-volumar imaging (EVI) of the brain at 3.0 T: first normal volunteer and
      functional imaging results.
AB  - OBJECTIVE: Our goal was to present the first echo-volumar brain images obtained
      at 3.0 T, together with the first functional imaging results using echo volumar
      imaging. MATERIALS AND METHODS: The results presented were obtained on volunteers
      using an in-house designed and constructed 3.0 T echo-planar/volumar imager.
      RESULTS: The results demonstrate the feasibility of obtaining snapshot volumar
      images comprising up to 64 x 64 x 8 voxels corresponding to a spatial resolution
      of 3.0 x 3.0 x 2.5 mm3. Results are also presented showing local cortical changes
      in signal in response to an external visual stimulus for both the left and the
      right brain hemispheres. CONCLUSION: The snapshot acquisition of a whole-volume
      data set has a number of advantages when considering motional effects or
      functional image changes that may involve time delays or phase effects within
      different cortical regions. Instantaneous acquisition of the whole data set means
      accurate phase information may be straightforwardly obtained.

PMID- 8537515
TI  - Rathke cleft cyst: CT, MR, and pathology of 23 cases.
AB  - OBJECTIVE: We report the radiologic findings in 23 cases of Rathke cleft cyst
      (RCC) and correlate them with the histopathology. MATERIALS AND METHODS: We
      reviewed the radiology and pathology of 23 cases of surgically treated RCC
      operated upon at our institution or referred in consultation. RESULTS: There
      appears to be a correlation between the MR and CT appearance of the cyst, the
      gross appearance of the cyst contents, and the histopathologic characteristics of
      the cyst lining. Some of the lesions demonstrated peripheral enhancement, which
      in two cases was clearly due to a peripherally displaced rim of pituitary tissue.
      CONCLUSION: The appearance of RCC with CT and MRI is variable, and radiologic
      diagnosis can be difficult. Imaging features such as a sellar epicenter, smooth
      contour, absence of calcification, absence of internal enhancement, and
      homogeneous attenuation or signal intensity within the lesion suggest the
      diagnosis of RCC. Rim enhancement does not correlate with the presence of
      squamous metaplasia, hemosiderin, or cholesterol within the cyst wall and is not
      consistently seen in cases with changes of mild, chronic inflammation. In some
      cases, rim enhancement is due to a peripherally displaced rim of pituitary
      tissue.

PMID- 8537516
TI  - CT and MRI of pleomorphic xanthoastrocytoma: unusual biologic behavior.
AB  - OBJECTIVE: Our goal was to present three cases of pleomorphic xanthoastrocytoma
      (PXA) with unusual radiographic, clinical, and pathologic aspects. MATERIALS AND
      METHODS: The imaging findings in three patients with proven PXA were reviewed and
      correlated with clinical information and review of pathologic material. Two
      females and one male were studied, ranging in age from 8 to 42 years old. All
      patients underwent MRI with gadolinium (0.1 mmol/kg). Two of the patients had
      serial MR studies. CT scans with and without contrast agent were also available
      for two patients. The medical records for all three patients were reviewed.
      Radiographic findings were correlated with pathologic material obtained at
      surgery. RESULTS: Seizure disorder was the initial presentation in two patients.
      The third patient presented with a lytic lesion of the calvarium. Radiographic
      features showed rapid progression of disease over 3 months in one patient. Rapid
      tumor recurrence (within 7 months) without malignant transformation was proven in
      another patient. While typical pathological features of PXA were evident in two
      cases, a mixed tumor consisting of PXA and other tissue components was identified
      in the third case. CONCLUSION: Although generally regarded as a benign lesion in
      the literature, PXA has potential for aggressive behavior. Rapid tumor recurrence
      can occur without malignant transformation. Radiographic features may evolve over
      a short period of time. Dura and bony calvarium are not necessarily respected.
      PXA can occur as a separate entity or as a tumor of mixed components.

PMID- 8537517
TI  - MR volumetry for monitoring intramuscular bromocriptine treatment in
      macroprolactinomas.
AB  - OBJECTIVE: To assess volumetric changes of pituitary prolactinomas, we applied a
      threshold-based segmentation algorithm in two patients during intramuscular
      bromocriptine treatment. MATERIALS AND METHODS: Tumor volumes were calculated
      from contiguous slices of a 3D GE sequence and from conventional SE images.
      RESULTS: After a single 50 mg i.m. bromocriptine administration, the prolactinoma
      volumes decreased by 25 and 35% within 7 and 11 days, respectively. Volume
      calculations from 3D GE images were more accurate than calculations from 3 mm 2D
      SE images, especially for smaller tumors. A decrease of prolactinoma size was
      paralleled by a decrease of serum prolactin levels and correlated with an
      improvement of visual field and endocrine function in both patients. The end of
      the bromocriptine effect was indicated by a reincreasing tumor volume, which was
      observed after 30 days in the first patients and after 43 days in the second
      patient. CONCLUSION: Our results suggest that MR volumetry represents a useful
      tool to monitor changes of prolactinoma volume during bromocriptine treatment and
      may improve the clinical management of these patients.

PMID- 8537518
TI  - 3D phase contrast EPI MR angiography of the carotid arteries.
AB  - OBJECTIVE: Our goal was to compare 3D phase contrast (PC) echo planar imaging
      (EPI) MRA of the carotid and vertebral arteries with conventional 3D PC in
      volunteers and patients. MATERIALS AND METHODS: The carotid arteries of 12
      volunteers were imaged with conventional and EPI 3D PC sequences. The visibility
      for each of seven carotid and four vertebral segments was qualitatively assessed.
      Signal intensity and homogeneity determinations were performed on the source
      images. Three patients with known carotid artery disease were also imaged with
      the same protocol. RESULTS: EPI reduced 3D PC data acquisition time from 459 to
      32 s (factor of 15). Both techniques permitted full assessment of the common
      carotid artery, the bifurcation, as well as the proximal internal carotid artery
      (ICA), external carotid artery (ECA), and vertebral arteries. Visualization of
      the distal ICA/ECA and vertebral arteries was inferior with EPI compared with the
      conventional acquisition. In all patients, lesions as established by X-ray
      angiography were seen to equal advantage with both techniques. CONCLUSION: EPI 3D
      PC MRA renders diagnostic images of the proximal carotid system. The considerable
      reduction in data acquisition time must be weighed against poorer image quality.

PMID- 8537519
TI  - Evaluation of vascular compression in trigeminal neuralgia by 3D time-of-flight
      MRA.
AB  - OBJECTIVE: Our goal was to assess the usefulness of 3D images in the preoperative
      evaluation of 16 patients with surgically confirmed trigeminal neuralgia.
      MATERIALS AND METHODS: The axial source images from 3D TOF MRA were evaluated for
      a total of 32 sides by two observers in a blinded manner, focusing on the
      presence of the neurovascular compression and the identification of compressing
      vessels. All 3D images including coronal orientation and gadolinium-enhanced
      images were reviewed retrospectively by another two observers together with the
      surgical findings. RESULTS: In the blinded study with axial 3D images, the
      sensitivity was 75 and 75% with a specificity of 75 and 69% for observers A and
      B, respectively. By reviewing the coronal images, the relationship between
      trigeminal nerve and vessels became clearer, especially in sandwich-type
      compression. With gadolinium-enhanced images, three vessels that were not shown
      in the nonenhanced images could be identified. On the asymptomatic side, vascular
      compression could not be excluded retrospectively in five cases. CONCLUSION:
      Nonenhanced axial images may not display small arteries or veins that are
      compressing the trigeminal nerve. Gadolinium enhancement will be necessary for
      those patients without demonstrable compression on nonenhanced examination.
      Coronal images are also helpful in the evaluation of vascular compression.

PMID- 8537520
TI  - Unusual pattern of a deep developmental venous anomaly on CT and MR studies.
AB  - OBJECTIVE: This article focuses on an unusual cross-sectional imaging pattern of
      a deep developmental venous anomaly (DVA). Since these anomalies are
      nonpathologic, they must not be interpreted as a disease that requires further
      costly workup and potentially injurious procedures (cerebral angiography).
      MATERIALS AND METHODS: Two women aged 19 (Case 1) and 30 (Case 2) years sought
      medical evaluation for severe headaches. Both patients underwent CT, MRI, and
      conventional cerebral angiography. Case 1 also underwent MR venography. RESULTS:
      The diagnosis of an unusual DVA in Case 1 was confirmed only after conventional
      catheter angiography and a follow-up MR venogram. In Case 2 the diagnosis was
      inferred based upon the CT, MRI, and conventional angiography results and the
      marked similarity to Case 1. The presumptive diagnosis in Case 2 would not have
      been made with confidence without the prior experience of managing Case 1.
      CONCLUSION: DVAs (venous angiomas) are extreme variations in the pattern of
      intracranial venous drainage. These two case reports highlight an unusual pattern
      of this benign entity. Individuals interpreting cross-sectional imaging studies
      should be cognizant of this pattern.

PMID- 8537521
TI  - The "dural tail sign" in MRI of spinal meningiomas.
AB  - OBJECTIVE: Evaluation of "dural tail sign" in spinal meningiomas with gadolinium
      enhanced MRI in sagittal, axial, and especially coronal planes. MATERIALS AND
      METHODS: On a 0.5 T system, sagittal and axial T1 spin echo images (TR/TE 550/22)
      and sagittal T2 turbo spin echo images (TR/TE 2855/150) of the thoracolumbar
      spine were acquired. After administration of gadolinium (0.1 mmol/kg), sagittal,
      axial, and coronal T1 spin echo images (TR/TE 500/30) were acquired at the area
      of the tumors. RESULTS: The nonenhanced images demonstrated intradural and
      extramedullary tumors with a signal intensity in the T1 images a little higher
      than the adjacent spinal cord. After the administration of gadolinium,
      homogeneous enhancement of the tumors was seen. An even stronger enhancement was
      noticed at the borders of the tumors with the adjacent meninges, seen in the
      sagittal, axial, and even better in the coronal views. Both tumors proved
      histologically to be meningiomas. CONCLUSION: In evaluating spinal meningiomas, a
      gadolinium enhanced MRI of the spine in sagittal, axial, and especially coronal
      planes should be performed to detect "dural tails," very suggestive of
      meningioma. These three scanning planes are necessary to visualize the
      localization and extent of the tumors and their tails prior to surgery.

PMID- 8537522
TI  - MRI/myelographic localization of fistulous tract in spinal dural arteriovenous
      malformations prior to arteriography.
AB  - OBJECTIVE: Our goal was to use currently available imaging methods to localize
      the fistulous tract of spinal dural arteriovenous malformations (SDAVMs) prior to
      arteriography. MATERIALS AND METHODS: Two middle-aged men showed MR findings
      indicative of a SDAVM. In the first patient coronal T2-weighted (T2W) imaging
      identified the engorged draining radiculospinal vein and traced it back to the
      intervertebral foramen site where the "nidus" was located. Then, axial T2W
      imaging was performed at the level of the involved intervertebral foramen. In the
      second patient MRI failed to demonstrate the nidus; myelography was carried out
      and showed the course of the abnormal intraspinal vein. RESULTS: Successful
      MR/myelographic demonstration of the nidus (Case 1) or the abnormal intraspinal
      vein (Case 2) simplified and abbreviated the later studies. CONCLUSION: With MRI
      and/or myelography we were able to localize the site of the fistulous tract in
      the two cases of SDAVM prior to spinal arteriography.

PMID- 8537524
TI  - Spiral versus conventional CT in routine examinations of the neck.
AB  - OBJECTIVE: Our goal was to optimize the efficiency of contrast material (CM)
      application in routine examinations of the neck by the use of spiral CT and slow
      power injection. MATERIALS AND METHODS: Dynamic studies were performed in 14
      patients to establish a set protocol for spiral CT examinations of the neck.
      Prospectively, 100 patients were examined either by use of the spiral technique
      with 100 ml CM (30 g iodine) injected in two phases or in conventional CT with
      150 ml CM (45 g iodine). Vascular and parenchymal enhancement was evaluated at
      three distinct levels of the neck. RESULTS: Despite the reduced CM volume in
      spiral CT, vascular enhancement was significantly higher at all three levels.
      Parenchymal enhancement was comparable in both groups. CM exploitation in
      vascular opacification (ratio of mean enhancement to applied CM volume) was 0.87
      in spiral CT compared with 0.43 in conventional CT. CONCLUSION: Spiral CT
      significantly increases the efficiency of CM application and is well suited for
      routine examinations of the neck.

PMID- 8537523
TI  - Comparison of dynamic and spiral CT for imaging the glottic larynx.
AB  - OBJECTIVE: Our goal was to prospectively compare dynamic CT (DCT) and spiral CT
      (SCT) for evaluating patients with suspected abnormalities of the glottic region
      and correlate the observed differences between the two techniques with phantom
      measurements. MATERIALS AND METHODS: Thirty-one patients suspected of having
      laryngeal abnormalities underwent DCT and SCT. The studies were evaluated by two
      head and neck radiologists for lesion detection, visualization of the paraglottic
      fat planes (PGFPs), motion artifact, respiratory misregistration, and overall
      image quality. Slice sensitivity profile (SSP) and image noise were measured for
      DCT and SCT for the imaging parameters used in this study. RESULTS: Artifacts due
      to motion and respiratory misregistration were reduced with SCT compared with
      DCT. Laryngeal abnormalities and the adjacent PGFPs were better visualized with
      DCT than SCT. With use of similar imaging parameters, SSP and image noise were
      both increased with SCT compared with DCT. CONCLUSION: SCT produces high quality
      images of the larynx with less motion and respiratory misregistration artifacts
      than DCT. DCT allows better visualization of lesions and subtle anatomic features
      of the glottic region. SCT may substitute for DCT in laryngeal imaging.

PMID- 8537525
TI  - Clinical evaluation of pulmonary 3D time-of-flight MRA with breath holding using
      contrast media.
AB  - OBJECTIVE: Our goal was to evaluate the clinical utility of pulmonary 3D TOF MRA
      using a contrast medium and breath holding. MATERIALS AND METHODS: To determine
      an optimal imaging time in a pilot study, 30 sequential axial images were
      obtained for each of 18 patients by using a turbo fast low angle shot sequence
      immediately after a bolus injection of 5 ml Gd-DTPA. MRA consisted of five
      sequential MR scans performed using a 3D fast imaging with steady-state
      precession sequence on 13 patients. The imaging start time after a bolus
      injection of 10 ml Gd-DTPA was determined from the results of the pilot study. We
      hoped that the acquisition of the center of k-space of the first MRA was matched
      to the period of maximum effect of the first pass bolus for the pulmonary
      arteries. RESULTS: In a pilot study on average, pulmonary artery signal
      intensities were relatively high from 10.4 to 20.7 s after the contrast medium
      injection. The MR angiograms obtained at the optimal time were superior to those
      that followed. All pulmonary trunks and the right and left main pulmonary
      arteries were accurately recognized. MRA had a sensitivity of 80.0%, a
      specificity of 95.0%, and an accuracy of 94.5% for the detection of segmental
      artery stenosis or occlusion. Abnormal vessels were visualized in both patients
      with pulmonary sequestration. CONCLUSION: Pulmonary 3D TOF MRA using breath
      holding and a contrast medium is useful in demonstrating proximal pulmonary
      vasculature and pulmonary sequestration.

PMID- 8537526
TI  - Necrotizing sarcoid granulomatosis: computed tomography and pathologic findings.
AB  - OBJECTIVE: To describe the CT findings and corresponding pathological findings of
      necrotizing sarcoid granulomatosis (NSG). MATERIALS AND METHODS: We reviewed the
      high-resolution CT and macroscopic and histologic findings in three
      pathologically proven cases of NSG. RESULTS: The CT findings consisted of one
      case each with single nodule, multiple nodules, and parenchymal opacification.
      The abnormalities were peribronchovascular or subpleural in distribution.
      Histologically, all patients had sarcoid-like granulomas with central necrosis
      and granulomatous vasculitis. The CT findings correlated closely with the gross
      pathologic findings. CONCLUSION: We conclude that the CT manifestations of NSG
      reflect the variable macroscopic pathologic findings.

PMID- 8537527
TI  - Spirometrically controlled quantitative CT for assessing diffuse parenchymal lung
      disease.
AB  - OBJECTIVE: Assessment of lung attenuation by CT reflects changes in the air-to
      tissue ratio of the lung. We have analyzed the interdependence of intrathoracic
      gas volume, lung morphology, and functional disorder by high resolution CT (HRCT)
      to assess quantitative disease threshold in obstructive and restrictive diffuse
      lung disease. MATERIALS AND METHODS: Pulmonary HRCT was performed on 24 healthy
      volunteers, 11 patients with chronic obstructive pulmonary disease (COPD), and 16
      patients with idiopathic lung fibrosis (IPF). HRCT measurement was standardized
      by taking three scans at the carina +/- 5 cm and by defining inspiration levels
      by percent vital capacity (VC) via spirometrically gating to the scanner.
      RESULTS: The mean lung density at 50% VC (DL50) for healthy subjects was -819 +/-
      3.8 (mean +/- SEM) HU. In contrast, COPD DL50 was lower, averaging -861 +/- 6.4
      HU, and the IPF DL50 was considerably higher (-731 +/- 17.7 HU), both
      significantly different (p < 0.001) compared with the control group. The accuracy
      of quantitative HRCT at different inspiration levels was evaluated by scanning
      the basal layer at 20, 50, and 80% VC. The control values were -747 +/- 5.6, -816
      +/- 3.6, and -855 +/- 3.0 HU, respectively, which were significantly higher (p <
      0.001) than those seen in COPD patients at 20 and 50% VC. Again, the IPF patients
      exhibited increased lung density (p < 0.001) at all inspiratory levels.
      Discrimination power was best among all cohorts at 20 and 50% VC. Position
      dependent artifacts on lung density were quantified by the anteroposterior
      density gradient (APG). Irrespective of the underlying disease, APG at 50 and 80%
      VC was similar, but was up to twofold higher at 20% VC, indicating that
      quantitative estimates near RV may misrepresent mean lung density. CONCLUSION:
      Our data indicate that quantitative HRCT measurements should be performed not
      near full inspiration or expiration, but at an intermediate degree of lung
      inflation, e.g., 50% VC, for reasons of accuracy, intra- and intersubjective
      comparability, and feasibility. We conclude quantitative HRCT to be a sensitive
      tool for the evaluation of diffuse parenchymal lung disease.

PMID- 8537528
TI  - CT reconstruction algorithm selection in the evaluation of solitary pulmonary
      nodules.
AB  - OBJECTIVE: We have observed a significant CT artifact in the evaluation of lung
      nodules that occurred with the use of high-spatial-frequency reconstruction
      algorithms. We have seen this lead to a false-positive diagnosis of calcification
      in a small uncalcified lung nodule. Because of the seriousness of
      misinterpretation of benign calcification in an uncalcified nodule, we reviewed
      the various effects of several reconstruction algorithms on different scanners.
      MATERIALS AND METHODS: Using high-spatial-frequency, smoothing, and intermediate
      reconstruction algorithms, we studied standardized cylinders in a CT reference
      phantom and lung nodules in eight patients. Algorithms on four CT scanners were
      analyzed. RESULTS: We found peripheral edge enhancement artifact on some CT
      images of phantom cylinders and uncalcified lung nodules. The images with edge
      enhancement artifact were obtained from two scanners with the use of high-spatial
      frequency algorithms (Picker 1200 SX and GE HiSpeed Advantage). CONCLUSION: Use
      of high-spatial-frequency reconstruction algorithms for the analysis of lung
      nodules with thin-section CT may lead to an erroneous diagnosis of calcification.

PMID- 8537529
TI  - Effect of slice acquisition direction on image quality in thoracic MRI.
AB  - OBJECTIVE: We tested the basic observation that imaging the heart and pericardium
      in systole improves image quality compared with that in diastole. MATERIALS AND
      METHODS: Twenty consecutive patients and two volunteers underwent sequential ECG
      gated short TE transaxial prospective multislice SE MRI with both caudocranially
      and craniocaudally directed slice prescriptions, keeping other imaging parameters
      constant. Images of the heart and pericardium were obtained in systole and
      diastole and examined by three independent reviewers for image quality. RESULTS:
      In the lower mediastinum, cardiac structures and the pericardium were better seen
      in 49 of 57 individual evaluations when imaged in systole, 15 of which were
      judged markedly better. Vascular structures and the pericardium in the upper
      mediastinum were imaged equally well with both prescriptions. CONCLUSION: The
      findings suggest that in systole, the more mobile heart can maintain a more
      consistent shape during the acquisition of successive phase-encoding steps and
      preserve luminal flow void, factors critical to optimizing image quality in the
      transaxial plane.

PMID- 8537530
TI  - Intramural invasion of gastric cancer: evaluation by CT with water-filling
      method.
AB  - OBJECTIVE: Our goal was to clarify the ability of CT to evaluate intramural
      invasion of gastric cancer. MATERIALS AND METHODS: We reviewed bolus-enhanced CT
      images performed with orally administered 400-600 ml of water in 59 early gastric
      cancers and 22 advanced gastric cancers mimicking early gastric cancers
      macroscopically. RESULTS: CT was able to reveal 49% of early gastric cancers and
      68% of advanced gastric cancers mimicking early cancers. Twenty-seven gastric
      tumors were detected in two or three layered structure of wall. Morphologic
      features of early gastric cancers are strong enhancement without wall thickening
      and thickened inner layer with normal middle and outer layers. Morphologic
      features of early advanced gastric cancers are a thickened wall with disappeared
      middle and outer layers and transmural enhancement with wall thickening. If one
      of these features was used to predict whether the tumor was early or early
      advanced gastric cancer in detected cases, specificity was 93-100%, sensitivity
      was 7-72%, and positive predictive value was 80-100%. CONCLUSION: We evaluated
      whether the wall pattern of gastric tumors on CT can provide useful information
      about intramural invasion.

PMID- 8537531
TI  - Detection of hypervascular hepatocellular carcinoma by dynamic MRI and dynamic
      spiral CT.
AB  - OBJECTIVE: Our goal was to evaluate the detectability of hypervascular
      hepatocellular carcinomas (HCCs) by multislice dynamic MRI and dynamic spiral CT.
      MATERIALS AND METHODS: Prior to transcatheter arterial chemoembolization (TACE)
      with iodized oil, the liver was subjected to T1- and T2-weighted SE-MRI,
      multislice dynamic MRI after intravenous bolus injection of Gd-DTPA, early phase
      imaging with spiral CT (dynamic spiral CT) after intravenous bolus injection of
      contrast medium (at a rate of 2 or 3 ml/s), and delayed phase CT in 64 patients
      with 208 HCC nodules. The detectability of HCCs by MRI and CT was evaluated
      retrospectively compared with CT after TACE as a gold standard. RESULTS: The
      detectability of nodules < 1 cm in diameter was superior with dynamic MRI (67%)
      and dynamic spiral CT (50%) in comparison with SE-MRI (26%) and delayed phase CT
      (11%) (p < 0.01). The detectability of these tumors with dynamic MRI was
      significantly superior to that with dynamic spiral CT using an injection rate of
      2 ml/s (p < 0.01), but not significantly different from that of dynamic spiral CT
      using a rate of 3 ml/s. CONCLUSION: Dynamic MRI and dynamic spiral CT are
      comparable for detecting hypervascular intrahepatic metastases of HCC.

PMID- 8537532
TI  - Qualitative evaluation of chronic diffuse liver disease by STIR MRI.
AB  - OBJECTIVE: The purpose of our study was to characterize the relationship between
      signal intensity on STIR MRI, histology, and liver function. MATERIALS AND
      METHODS: MRI was performed in 39 patients with chronic liver diseases [chronic
      persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC)]
      and 11 patients without liver dysfunction (normal). RESULTS: On STIR images, very
      low signal intensities compared with those of the spleen were seen in all 11
      normal livers (100%), and brighter intensities were seen in chronic diffuse liver
      diseases (10 patients with CPH, 11 patients with CAH, and 18 patients with LC)
      (100%). The higher the signal grade on STIR images (moderate, marked), the more
      advanced was the chronic diffuse liver disease (p < 0.02). The levels of serum
      glutamic-oxaloacetic and glutamic-pyruvic transaminase increased in parallel with
      increasing signal intensity on STIR images (both p < 0.01). CONCLUSION: We found
      that the signal intensity of liver on STIR images appeared to be associated with
      the degree of histologic and/or clinical severity in patients with chronic liver
      disease.

PMID- 8537533
TI  - Segmented areas of increased attenuation in the liver caused by right adrenal
      tumors: CT features.
AB  - OBJECTIVE: Our goal was to describe attenuation differences bordered by a
      straight line in the right hepatic lobe on enhanced CT in patients with right
      adrenal tumors and to discuss the cause of this appearance. MATERIALS AND
      METHODS: Three patients showing attenuation differences bordered by a straight
      line were discovered in the CT files of 26 cases of right adrenal tumor over 3 cm
      in diameter. All CT scans were examined by incremental dynamic study. RESULTS:
      Two patients had large zone of hyperattenuation in the right lobe bordered with a
      straight line intersecting both anterior branches of the right portal vein and
      the inferior vena cava (IVC). A third patient and one of the two patients
      mentioned already had zones of relative hyper- and hypoattenuation in the medial
      portion of the posterior hepatic segment, respectively. All three patients had
      large right adrenal tumors, which severely compressed the right hepatic vein near
      its confluence with the IVC and/or the IVC in or below its intrahepatic portion.
      The distribution of attenuation differences was similar to the hyperattenuation
      at CT arteriography or perfusion defect at CT arterial portography under
      temporary balloon occlusion of the right hepatic vein and inferior right hepatic
      vein, respectively. CONCLUSION: Straight-bordered attenuation differences within
      the right hepatic lobe at dynamic CT can be caused by compression of the right
      hepatic vein by large right adrenal tumors.

PMID- 8537534
TI  - Anterior extension of acute pancreatitis: CT findings.
AB  - OBJECTIVE: The purpose of this study is threefold: (a) to specify the pathway of
      the extension of pancreatitis to the anterior abdominal wall, which is clinically
      famous as the Cullen sign; (b) to assess if this pattern of involvement affects a
      patient's prognosis; and (c) to seek its association with the inflammatory
      processes that take place in the vicinity of the pancreatic head. MATERIALS AND
      METHODS: The CT findings of 277 patients with acute pancreatitis were
      retrospectively reviewed. RESULTS: Inflammatory changes involved the anterior
      abdominal wall in 5 of 277 cases (1.8%) with acute pancreatitis. Inflammatory
      processes seemed to have been delivered to the anterior abdominal wall from the
      pancreatic head and the hepatoduodenal ligament and along the falciform ligament.
      The probable triggers of acute pancreatitis in such cases were endoscopic
      retrograde cholangiopancreatography in two cases, alcohol intake in one case, and
      one case unknown. Three of five cases had proven or suspected choledocholithiasis
      or cholelithiasis. All five patients got well after proper treatments for acute
      pancreatitis. CONCLUSION: The results of our review suggest that the anterior
      extension of acute pancreatitis does not directly mean extensive retroperitoneal
      involvement of the phlegmon or pseudocysts nor fatal prognosis either and that
      this style of extension might be associated with inflammatory processes that
      occur around the pancreatic head.

PMID- 8537535
TI  - Depiction of pelvic fractures using 3D volumetric holography: comparison of plain
      X-ray and CT.
AB  - OBJECTIVE: The goal of this study was to demonstrate the feasibility and test the
      diagnostic performance of a new technology, 3D volumetric holography, for imaging
      pelvic fractures. The management of pelvic fractures may be complex, and advanced
      imaging studies such as CT are frequently indicated. Multiplanar CT reformations
      and 3D renderings provide clinically useful and complementary display of the
      directly acquired CT data. With the recent availability of volumetric multiple
      exposure holograms, produced from serial image data, it is now possible to
      produce true 3D images of the pelvis. In the hologram, one may view the CT data
      in 3D or as individual planar slices constituting the whole 3D pelvis. The
      diagnostic performance of the volumetric multiple exposure holograms was tested
      against routine radiography, CT, and 3D volumetric CT reconstructions. MATERIALS
      AND METHODS: Routine radiography and CT were performed in 15 patients with
      suspected pelvic fractures. Volumetric multiple exposure holograms and 3D
      volumetric CT reconstructions were created from the CT data. Axial and
      multiplanar reformation CT images were used as the standard for fracture,
      diastasis, and intraarticular fragment detection. RESULTS: Radiograms detected 39
      of 50 of the fractures and diastases and no intraarticular fragments. The 3D CT
      reconstructions and the holograms viewed as 3D objects alone missed two small
      fractures of the anterior column and one hip with intraarticular bone fragments.
      When the volumetric multiple exposure holograms were viewed as a 3D object and as
      individual planar slices constituting the whole, their results were the same as
      the standard. CONCLUSION: Volumetric multiple exposure holograms were as
      sensitive and specific as axial CT and multiplanar reformations in detecting
      fracture pathology. By containing and making available, from one image, both
      planar and 3D information, volumetric multiple exposure holograms detected subtle
      anatomical features that were hidden by overlapping structures in the radiographs
      and the 3D CT images.

PMID- 8537536
TI  - Measurement of 129Xe T1 in blood to explore the feasibility of hyperpolarized
      129Xe MRI.
AB  - OBJECTIVE: The major obstacle to the use of 129-xenon (I = 1/2) as a new source
      of contrast in magnetic resonance is its low sensitivity. The hyperpolarized
      129Xe-MRI technique using laser optical pumping of rubidium promises to resolve
      this problem. The potential of xenon-based MRI for the body tissues other than
      the lung air spaces depends on the 129Xe polarization lifetime (T1) in the blood
      at a magnetic field of commonly available clinical MRI systems. MATERIALS AND
      METHODS: Xenon with natural abundance of 129Xe (26%) was dissolved in human blood
      and studied at 36 degrees C in a 2.35 T 40 cm bore MRI spectrometer (27.6 MHz).
      Zeeman relaxation (T1) of six blood samples was measured by the progressive
      saturation method for periods of 4-8 h each. RESULTS: NMR spectra revealed two
      peaks at 216.0 ppm (A) and 194.0 ppm (B) relative to the xenon gas above the
      blood volume. Assignment and 129Xe T1 values were 4.5 +/- 1 s for red blood cells
      (A), 9.6 +/- 2 s for plasma (B) and 11.9 +/- 1.6 s for xenon gas at atmospheric
      oxygen pressure. Xenon dissolved in distilled water appears at 189.8 ppm and has
      T1 = 26.3 +/- 1.4 s. CONCLUSION: These relaxation times, though shorter than
      expected, are comparable to the transport time of blood, and are long enough to
      encourage use of hyperpolarized xenon for MRI studies in tissues, in addition to
      lung.

PMID- 8537537
TI  - Early detection of cerebral ischemic lesion using diffusion-weighted MRI.
AB  - We performed serial diffusion-weighted imaging (DWI) in a patient with right
      middle cerebral arterial occlusion using 1.0 T MRI. The initial DWI demonstrated
      suppression of water diffusion in the gray matter in the ischemic lesion as a
      high signal area 4 h after stroke onset, when T2-weighted imaging failed to
      detect any parenchymal injury. Repeat DWI 9 h after onset demonstrated the whole
      infarct, whereas it was not demonstrated by T2-weighted imaging until 48 h.
      Furthermore, the regional apparent diffusion coefficient (ADC) had already
      decreased significantly in both the gray and white matters of the ischemic lesion
      4 h after onset, even though hyperintensity was not visible in the white matter
      on the DWI. The features in this case indicate that DWI in conjunction with the
      assessment of regional ADC can provide important information regarding the
      evolving infarct at a very early stage even when a relatively low tesla
      clinically available MRI unit is used.

PMID- 8537538
TI  - Congenital agenesis/aplasia of the internal carotid arteries: MRA and SPECT
      findings.
AB  - Single photon emission CT (SPECT) and MRI and MR angiography studies were
      performed in a patient with right internal carotid artery (ICA) agenesis, left
      ICA aplasia, and multiple associated vascular abnormalities identified with
      digital subtraction angiography. Magnetic resonance angiography provided an
      excellent depiction of the extra- and intracranial vascular abnormalities. No
      evidence of brain lesions or perfusion defects was demonstrated with MRI and
      SPECT, despite the markedly altered vascular anatomy.

PMID- 8537539
TI  - Extradural failure in glioblastoma multiforme: MRI demonstration.
AB  - Glioblastoma multiforme is invariably associated with intracranial failure
      following conventional therapy. Extracranial as well as metastatic failure are
      rarely seen. Subtle extracranial abnormalities in most patients with glioblastoma
      multiforme are not indicative of convexity failure. However, in patients with
      high p53 and Ki67 immunoreactivity and in whom the dura was not closed at the
      time of craniotomy, the possibility of early extradural failure should be
      considered.

PMID- 8537540
TI  - Takayasu arteritis: palpable neck mass diagnosed by cross sectional imaging.
AB  - Takayasu arteritis is a chronic inflammatory disease of unknown origin. The
      disease is characterized by transmural inflammation and fibrosis; the arterial
      lesions affect mainly the aorta and great vessels and sometimes involve the
      pulmonary arteries and visceral vessels. Despite efforts to create criteria for
      clinical diagnosis, many patients still require angiography for complete
      evaluation and diagnostic confirmation. We describe a patient with a mass seen on
      CT and confirmed on MRI; angiography showed changes in the vertebral and carotid
      arteries. Our case proved to be an atypical presentation of Takayasu arteritis.

PMID- 8537541
TI  - Liver scarring associated with congenital absence of the right hepatic lobe: CT
      and MR findings.
AB  - We describe a patient with liver scarring associated with congenital absence of
      the right lobe of the liver. Computed tomography demonstrated a low density zone
      at the periphery of the liver that appeared hyperintense on T2-weighted MRI and
      markedly enhanced on contrast-enhanced T1-weighted imaging. Computed tomography
      during both arteriography and arterial portography demonstrated a differential
      blood supply to the low density zone, suggesting the diagnosis of liver scarring.
      Histological examination of a biopsy from this region disclosed periportal
      fibrosis and sinusoidal dilatation, confirming the diagnosis of liver scarring.

PMID- 8537542
TI  - Increased susceptibility to Bacillus thuringiensis associated with pyrethroid
      resistance in Bovicola (Damalinia) ovis (Phthiraptera Mallophaga: possible role
      of monooxygenases.
AB  - A comparison of the toxicity of Bacillus thuringiensis (Berliner) to pyrethroid
      susceptible and -resistant strains of Bovicola (Damalinia) ovis showed that B.
      thuringiensis and pyrethroid toxicity were inversely related. The B. ovis strain
      with an apparent monooxygenase-mediated pyrethroid resistance mechanism was
      significantly more susceptible to B. thuringiensis. Susceptibility to B.
      thuringiensis in both the pyrethroid-susceptible and -resistant strains was
      significantly reduced after administration of the monooxygenase inhibitor
      piperonyl butoxide. Susceptibility to B. thuringiensis in the pyrethroid
      susceptible strain was significantly enhanced after administration of a
      monooxygenase inducer, sodium phenobarbital. These results suggest that
      monooxygenases may be important in increasing the toxicity of B. thuringiensis
      against B. ovis. We discuss the potential use of B. thuringiensis to control
      pyrethroid-resistant lice.

PMID- 8537543
TI  - Physiological and nutritional responses of steers infested with varying densities
      of Amblyomma americanum (Acari: Ixodidae).
AB  - The effects of varying densities of lone star tick, Amblyomma americanum (L.), on
      measured physiological parameters of beef cattle in a controlled environment was
      determined. Steers were infested with either 0, 20, 60, or 120 pairs of adult
      ticks. Heart rate, respiration, rectal temperature, fecal and urine excretions,
      and water and feed consumption were monitored daily. Blood samples were taken
      every 3rd d to measure cortisol, total proteins, urea nitrogen, and glucose
      levels. Hematocrits were also taken at each blood sampling. Results showed that
      A. americanum evoked elevated heart rates. The other measured physiological and
      nutritional responses of parasitized steers were similar to the control steers.
      These results suggest that tick densities were too low to cause physiological
      stress under the conditions used in this study. The methodology precluded
      detection of the parameters measured. A. americanum does not affect the
      parameters measured, or that fluctuating environmental parameters and varying
      host nutritional states may play major roles in modulating the effect of A.
      americanum infestations on cattle in nature.

PMID- 8537544
TI  - Airborne insecticide residues after broadcast application for cat flea
      (Siphonaptera: Pulicidae) control.
AB  - Airborne residues of chlorpyrifos, propetamphos, and permethrin were measured up
      to 50 h after broadcast treatment for cat flea, Ctenocephalides felis (Bouche),
      control in residences. Type of insecticide, time after treatment, ventilation
      regime, and height above floor significantly affected airborne residues. Before
      spraying chlorpyrifos, residues were low or undetected. In nonventilated
      residences, chlorpyrifos residues peaked 0-6 h after treatment at 38 ng/liter,
      then slowly declined through 50 h. In ventilated residences, chlorpyrifos
      residues peaked from 2 to 10 h after treatment at 25-27 ng/liter, then declined
      to 8 ng/liter at 50 h. Propetamphos and permethrin residues in nonventilated
      residences peaked at 0-2 h at 32-40 and 40-44 ng/liter, respectively.
      Propetamphos peaked at 12-17 ng/liter at 0-2 h in ventilated residences.
      Permethrin was not detected in any of the samples in ventilated residences.
      Maximum airborne concentrations were 74 ng/liter chlorpyrifos, 49 ng/liter
      propetamphos, and 54 ng/liter permethrin.

PMID- 8537545
TI  - Pharaoh ant (Hymenoptera: Formicidae) colony development after consumption of
      pyriproxyfen baits.
AB  - Pharaoh ant, Monomorium pharaonis (L.), colonies were effectively controlled
      following ingestion of pyriproxyfen formulated in peanut butter oil.
      Pyriproxyfen, a juvenile hormone analog, reduced egg production in the queens,
      decreased the amount of brood due to delayed death in the eggs and larvae, caused
      death of pupae about 3 wk after treatment, and decreased the number of workers
      due to attrition and toxic effects. Queens, which continued to produce a small
      amount of eggs, eventually died. Queen death may have been caused by lack of
      workers required to tend them, old age or toxic effects. At concentrations of
      0.25, 0.5 and 1%, pyriproxyfen was more effective than the once commercially
      available bait, Pharorid (methoprene) for the control of the Pharaoh ant.

PMID- 8537546
TI  - Effects of maize weevils (Coleoptera: Curculionidae) on production of aflatoxin
      B1 by Aspergillus flavus in stored corn.
AB  - Insects play an important role as facilitators of the aflatoxin-producing fungus,
      Aspergillus flavus Link, in both preharvest and postharvest corn. The current
      study investigated the role of maize weevils, Sitophilus zeamais Motschulsky, in
      enhancing aflatoxin B1 content in stored corn. In laboratory experiments,
      aflatoxin B1 was quantified with an indirect enzyme-linked immunosorbent assay
      (ELISA) on corn following artificial infestation with adult weevils that had each
      been topically treated with 100 spores of A. flavus. Corn kernels infested with
      A. flavus-contaminated weevils had significantly higher levels of aflatoxin B1
      than A. flavus-inoculated corn without weevils. The presence of maize weevils
      resulted in increased kernel moisture content during incubation, and grain
      moisture was positively correlated with aflatoxin content across treatments
      receiving spores. Aflatoxin B1 levels were higher in corn treated with fungus
      contaminated weevils compared with corn that was mechanically damaged and
      inoculated with spores, which in turn had more aflatoxin than undamaged corn
      treated with spores. Aflatoxin B1 content in corn increased with time of weevil
      exposure from 7 to 21 d, but decreased after 28 d of exposure. Aflatoxin levels
      in infested corn increased significantly with increased numbers of A. flavus
      contaminated weevils. Maize weevils carried spores both internally and
      externally; however, substantial numbers of spores were intimately associated
      with the exoskeleton of adult weevils. These findings indicate that maize weevils
      facilitate the growth of A. flavus and aflatoxin production in corn by increasing
      surface area susceptible to fungal infection and increasing moisture content as a
      result of weevil metabolic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537547
TI  - In vitro comparative study of the antitumor effects of human interferon-alpha,
      beta and gamma on the growth and invasive potential of human melanoma cells.
AB  - We have studied the effects of interferon (IFN)-alpha, beta, and gamma in vitro
      on the growth and invasive potential of human melanoma SK-MEL-118 cells. The
      antiproliferative effects of IFNs were assessed by a quantitative regrowth assay
      in which cells were treated with IFNs at concentrations of 10(2), 10(3) or 10(4)
      IU/ml for 3 days (until day 4) and then further incubated without IFNs for 7 days
      (until day 11). The growth inhibitory effect of each IFN on melanoma cells was
      dose- and time-dependent. Among these three types of IFNs, however, IFN-beta
      exerted the strongest inhibitory effect on cell growth. To assess the anti
      invasive effect of each IFN on melanoma cells, we employed an in vitro assay
      system using matrigel-coated Transwell chambers. When cells were treated with
      10(2), 10(3), or 10(4) IU/ml of the three types of IFNs for 24 hours, the amount
      of tritiated thymidine incorporated into melanoma cells were treated for 24 hours
      with 10(4) IU/ml of IFN-beta or gamma prior to the assay, the number of cells
      that invaded the filter decreased by 40%; this decrease was only 10% with the
      same amount of IFN-alpha. Simultaneous addition of IFNs during the invasion assay
      was not effective in any combination. Only when the cells were pretreated with
      IFNs, antiinvasive effects against melanoma cells were exerted. IFN-alpha was
      less inhibitory than IFN-beta or gamma on proliferation and not at all inhibitory
      on invasion. Considering both the antiproliferative and antiinvasive effects of
      IFNs, our results suggest that IFN-beta has the strongest antitumoral effect on
      human melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537548
TI  - The safety and efficacy of low-dose tissue plasminogen activator in the treatment
      of systemic sclerosis.
AB  - The safety and efficacy of low-dose (10 mg) recombinant human tissue plasminogen
      activator (rhtPA: Activase: Genentech) was studied in 14 systemic sclerosis (SSc)
      patients. The patients were enrolled in a double blind, placebo-controlled
      crossover trial. Patients who met the inclusion criteria were enrolled in the
      study, given placebo or rhtPA, and then crossed over at 3 months. Assessment
      criteria included the Rodnan skin score; a daily patient diary to record side
      effects, frequency, and severity of Raynaud's episodes and activity; and
      pulmonary function tests. Ten mg of rhtPA (Genentech) was administered over a 4
      hour period using a myocardial infarction protocol. None of the patients
      experienced side-effects from the treatment protocol. No differences in the
      frequency or severity of Raynaud's episodes were noted during the two arms of the
      study. However, when the mean change of the Rodnan skin score in the placebo arm
      was compared to the rhtPA arm of the protocol, a significant difference was
      observed (0.8 vs. -5.4, p < 0.001). Three patients had moderate improvement and
      seven showed mild improvement. Mild deterioration or no change in study
      parameters was noted in 4 patients. This study has demonstrated that the
      administration of low-dose rhtPA is safe and is accompanied by modest improvement
      in symptoms of a subset of scleroderma patients.

PMID- 8537549
TI  - Electron microscopic observations of epithelioid cell granulomas experimentally
      induced by prototheca in the skin of mice.
AB  - Electron microscopic analysis was conducted on epithelioid cell granulomas
      experimentally induced by prototheca in the skin of mice. In BALB/c mice,
      epithelioid cell granulomas were easily induced. Each cell had a round nucleus
      with euchromatin on the margin, abundant cytoplasmic organelles, and particularly
      abundant rough endoplasmic reticulum (rER). Cells with a plasmacytoid appearance
      were the most common. Fibroblast-like epithelioid cells were sometimes observed.
      The whole body and cell membrane of an organism was usually within the cytoplasm
      of epithelioid cell. In ICR mice, epithelioid cell granulomas were not easily
      induced. Cells which had ingested whole organisms had spindle shaped and/or oval
      nuclei with marginated heterochromatin and with abundant dilated rER. Near
      completion of organism digestion, the cells had irregular and/or indented nuclei
      with marginated heterochromatin and often one or two distinct nucleoli. The
      cytoplasm was often replaced with numerous phagocytic vacuoles. At higher
      magnification, secondary lysosomes and Golgi complexes forming Golgi lamellae
      could be seen in the cells in which cytoplasmic organelles such as endoplasmic
      organelles and mitochondria were abundantly present. In contrast to the BALB/c
      mice, the remnants of digested organisms, split up into many small pieces, could
      be seen in the cytoplasm. The cells with a fibroblast-like appearance were most
      frequent, but plasmacytoid cells were sometimes observed. In the present study,
      the ultrastructural features of epithelioid cells in BALB/c and ICR mice clearly
      differed. Plasmacytoid cells were the most abundant in BALB/c mice, while
      fibroblast-like cells were in ICR mice.

PMID- 8537550
TI  - Cytokine profile of tumor cells in mycosis fungoides: successful treatment with
      intra-lesional interferon-gamma combined with chemotherapy.
AB  - Two cases of mycosis fungoides (MF) in the tumor stage were treated with intra
      lesional interferon-gamma (IFN-gamma) therapy. After systemic chemotherapy, intra
      lesional recombinant interferon-gamma was applied to the residual tumors. Intra
      lesional IFN-gamma was sufficiently effective in the treatment of MF tumors,
      especially small-sized ones. Reverse transcriptase polymerase chain reaction (RT
      PCR) analysis of messenger RNA expression of cytokines commonly detected
      interleukin-6 (IL-6) and IFN-gamma in the tumor cells before intra-lesional IFN
      gamma. However, in our study, tumor cells in these cases did not exhibit the
      definitive cytokine patterns of Th1 or Th2.

PMID- 8537551
TI  - Basal cell carcinomas of the auricular region: a study of 23 cases.
AB  - Basal cell carcinomas (BCCs) of the auricular region are not frequently reported,
      especially in the Japanese literature. Predisposing conditions such as sun
      exposure or frostbite are possibly involved in their development. In this study,
      we report our cases of auricular BCCs, discussing the obtained results, the
      possible significance of predisposing conditions, and the correlation with the
      histologic subtypes involved. Among 1094 patients with BCCs, auricular tumors
      were observed in 23 patients (2.1%), 4 women and 19 men. All of them were present
      on the external sun-exposed auricular side. Histologic patterns were nodular and
      micronodular (13 cases) and infiltrative (10 cases). No differences were observed
      between sexes. The relative degree of elastosis was higher in men than in women.
      Frostbite was recorded in 4 cases. The ear is an anatomical region that is
      heavily exposed to sun-light and equally prone to frostbite. Our data showed that
      all the lesions were located on the auricular region more or less exposed to
      sunlight. There was a recorded previous history of predisposing factors in most
      cases, and the high degree of elastosis suggests the involvement of these
      predisposing factors. Moreover, the high prevalence of infiltrative subtypes
      observed in our survey suggests a possible correlation between some histologic
      subtypes, sun-exposure, and frostbite. The differences between the relatively
      high number of auricular BCCs reported in the literature in contrast with the
      Japanese observations suggest the involvement of social or local conditions.

PMID- 8537552
TI  - Low expression of adhesion molecules in a case of cutaneous T-cell lymphoma.
AB  - A case of cutaneous T-cell lymphoma (CTCL) with low expression of the adhesion
      molecules lymphocyte function-associated antigen-1 (LFA-1), intercellular
      adhesion molecule-1 (ICAM-1), and very late antigen-4 (VLA-4) is described. The
      patient was a 90-year-old man with red round homogeneous tumors on his scalp,
      trunk, and extremities. He had no history of definite erythema or plaque stage. A
      biopsy sample taken from a tumor revealed massive infiltration of atypical
      lymphocytes in the reticular dermis and subcutis with a definite clear zone. The
      atypical lymphocytes were medium-sized with slightly convoluted nuclei.
      Immunohistochemically, the infiltrates showed the phenotype of so-called memory T
      cells. On the basis of these features, the case was diagnosed as CTCL. Expression
      of LFA-1, ICAM-1 and VLA-4 on the infiltrates was 9%, 13% and 11%, respectively,
      which is much lower than that in classic mycosis fungoides. This finding suggests
      that loss of these adhesion molecules may contribute to loss of epidermotropism
      in the advanced stage of CTCL.

PMID- 8537553
TI  - Recurrent dermatofibrosarcoma protuberans with myxoid and fibrosarcomatous
      changes paralleled by loss of CD34 expression.
AB  - A 38-year-old woman complained of recurrent nodules on her anterior chest wall.
      She noticed the first nodule at the age of 12 and has since undergone surgical
      removal a total of 31 times. Finally, wide resection of parts of the rib
      cartilage and sternum and chest wall reconstruction were required.
      Histopathological examination of a series of surgical specimens were reevaluated.
      Immunohistochemical staining of the tumors by anti-CD34 antibody provided a
      definite diagnosis of dermatofibrosarcoma protuberans (DFSP). A noteworthy result
      was that her DFSP did not always express CD34; the recurrent tumors with myxoid
      and fibrosarcomatous changes lost their CD34 expression.

PMID- 8537554
TI  - Necrotizing fasciitis in association with hyperimmunoglobulin E syndrome.
AB  - A case of necrotizing fasciitis in association with hyperimmunoglobulin E (HIE)
      syndrome is reported. The patient was a 17-year-old Japanese boy with a clinical
      history of recurrent skin and pulmonary infections and eczematoid dermatitis,
      markedly elevated serum levels of IgE, and coarse facies. He had a gangrenous
      swelling on the lower abdominal wall, and his general condition was poor with
      high fever. The involved site was accompanied by subcutaneous gas; the culture of
      the pus of the lesion grew anaerobes without mixed growth of Staphylococcus
      aureus. Exhaustive debridement of necrotic fascia, which extended much farther
      than the gangrenous area, and administration of antibiotics had a curative effect
      on the gangrenous soft tissue infection. To the best of the authors' knowledge,
      this is the first published case of necrotizing fasciitis in association with HIE
      syndrome.

PMID- 8537555
TI  - Piroxicam induced Stevens-Johnson syndrome.
AB  - Stevens-Johnson syndrome in a 63-year-old Japanese woman is described. Oral
      provocation test revealed the causative agent to be piroxicam.

PMID- 8537556
TI  - Saphenous vein graft donor site dermatitis in Japan.
AB  - Four cases of saphenous vein graft donor site dermatitis are reported from Japan
      for the first time. The patients were four Japanese men aged from 57 to 69. They
      noted pruritic eruptions along the lower extremity scar after coronary artery
      bypass graft surgery using the autogenous saphenous vein. The eruptions appeared
      mainly on and around the lower end of the venectomy scars from 1.5 to 9 months
      after graft operations performed at three different hospitals. All four patients
      showed an objective sensory deficit of the saphenous nerve around the saphenous
      vein incision scar, although none of them complained of saphenous neuralgia
      subjectively. Histologically, two patients showed mild epidermal acanthosis,
      spongiosis, intraepidermal blisters, and perivascular infiltration of lymphocytes
      and a few eosinophils around dermal blood vessels. The eruption responded well to
      topical corticosteroids in all cases, although it recurred again in two patients.
      The entity is characterized by a subacute (belatedly appearing, then slowly
      disappearing) dermatitis and a mild sensory deficit of the saphenous nerve.
      Apparently, mild impediment of the saphenous nerve due to an ablational procedure
      of saphenous venectomy can play a role in causing saphenous vein graft donor site
      dermatitis.

PMID- 8537557
TI  - Psychosomatic treatment of a case of chronic urticaria.
AB  - A 35-year-old Japanese woman presented with urticaria in January of 1992. As her
      symptoms gradually became worse, she came to our hospital in March of that year.
      I treated her with various combinations of antihistaminics and antiallergics.
      However, her symptoms did not respond and continued to deteriorate. Although her
      blood was analyzed in an attempt to identify antigenic or physical factors, no
      positive data were obtained. Because three kinds of psychological tests showed
      that the patient was highly anxious and depressive, I additionally treated her
      with psychotropics and psychotherapy in May of 1994. After a month, the symptoms
      began to disappear. She has since been free from the symptoms while taking
      medicine only twice a week. Our group recently presented the efficacy of
      psychotropics in patients with chronic urticaria. This case suggests that highly
      anxious or depressive cases with chronic urticaria should be treated not only
      dermatologically, but also psychologically.

PMID- 8537558
TI  - Disseminated epidermolytic acanthoma with disseminated superficial porokeratosis
      and verruca vulgaris in an immunosuppressed patient.
AB  - A 40-year-old man who had received long term immunosuppressive treatment for 14
      years following kidney transplantation developed multiple skin lesions on both
      antecubital fossae, scalp, and both lower extremities. Histopathologic findings
      from three skin regions revealed characteristic features of epidermolytic
      hyperkeratosis, verruca vulgaris, and disseminated superficial porokeratosis,
      respectively. Although immunocompromised individuals may demonstrate verruca
      vulgaris or porokeratosis, disseminated epidermolytic acanthoma (DEA) has not
      been reported to be associated with immunosuppressed status. We suggest that
      immunosuppression may play a role in the pathogenesis of DEA, as shown in our
      case.

PMID- 8537559
TI  - Werner's syndrome associated with basal cell epithelioma.
AB  - A Japanese female with Werner's syndrome associated with basal cell epithelioma
      is reported. Werner's syndrome is prone to malignancy, and many such cases have
      been reported. However, basal cell epithelioma is rare in Werner's syndrome. In
      the presented case, a black nodule about 2 cm in diameter with erosion developed
      on her abdomen. The histology revealed the findings of basal cell epithelioma.

PMID- 8537560
TI  - The origin of pilonidal sinus: a case report.
AB  - The etiology of pilonidal sinus remains controversial. Some think it is
      congenital, and others think it is acquired. It is difficult to distinguish
      acquired pilonidal sinus from congenital, because infection almost always
      complicates both. We report here one case of acquired pilonidal sinus
      unaccompanied by infection. Histological examination showed that no epidermis or
      hair follicle was present in the inner wall of the sinus. This case shows that
      acquired pilonidal sinus is due to invasion of external hairs and that this
      condition needs to be distinguished from congenital pilonidal sinus.

PMID- 8537561
TI  - Reticular erythematous mucinosis syndrome associated with psoriasis-like
      eruptions.
AB  - We report a case of reticular erythematous mucinosis syndrome associated with
      psoriasis-like eruptions. Although the two skin diseases are clinically distinct,
      they may be related in some ways.

PMID- 8537562
TI  - Successful treatment of pyoderma gangrenosum with nicotine chewing gum.

PMID- 8537563
TI  - Tinea incognito mimicking red face and red ear.

PMID- 8537564
TI  - Eating disorders in adolescents: a model for broadening our perspective.

PMID- 8537566
TI  - Predicted and measured resting metabolic rate of male and female endurance
      athletes.
AB  - OBJECTIVE: To measure the resting metabolic rate (RMR) of a group of endurance
      trained male and female athletes and to compare it with values predicted using
      published equations. DESIGN: RMR was measured twice: 1 week apart for the men and
      approximately 1 month apart for the women. RMR was predicted using equations of
      Harris and Benedict, Owen et al, Mifflin et al, and Cunningham. SUBJECTS/SETTING:
      Subjects were 37 trained endurance athletes (24 men, 13 women) who had
      participated in studies previously completed in our laboratory. MAIN OUTCOME
      MEASURES: The primary outcome measure was the comparison of predicted RMR with
      measured RMR. An exploratory procedure for the determination of predictive
      variables in these athletes was also performed. STATISTICAL ANALYSES PERFORMED:
      The Root Mean Squared Prediction Error method was used to compare predicted RMR
      with measured RMR. The maximum R2 procedure method was used to determine the best
      possible combination of four variables that explained the largest amount of
      variance in RMR. RESULTS: The Cunningham equation was found to predict measured
      RMR most accurately (within 158 kcal/d for men and 103 kcal/d for women). Fat
      free mass was the best predictor of RMR in men, whereas energy intake was the
      best predictor in women. APPLICATIONS/CONCLUSIONS: The Cunningham equation
      provides an accurate estimate of RMR when determining energy needs of highly
      active people. Equations specific to athletes need to be developed. Factors in
      addition to body weight, height, and age should be investigated as possible
      predictor variables in athletes.

PMID- 8537565
TI  - Evaluation of predicted and measured energy requirements in burned children.
AB  - OBJECTIVE: The energy predictions of nine calculations for pediatric patients
      were compared with measured resting energy expenditure (MREE) by means of
      indirect calorimetry to determine the optimal means of energy projection in the
      burn population younger than 3 years of age. METHODOLOGY: Nutritional sufficiency
      and maintenance of preburn weight were factors in the confirmation of energy
      needs. Demographic factors were also studied: preburn weight, percent burn,
      percent third-degree burn, and age. Group 1 consisted of 24 patients younger than
      3 years of age (range = 7 months to 2.6 years) with a percent burn of 30.6 +/-
      2.0 and percent third-degree burn of 21.9 +/- 2.6. Group 2, consisting of 24
      patients 5 to 10 years old matched by percent burn and percent third-degree burn,
      was included to determine whether differences between actual and projected needs
      were evident in older, prepubescent patients. STATISTICAL ANALYSIS: Analysis of
      variance was used to ascertain the most reliable multiplier for MREE needed to
      maintain at least 95% of preburn weight at discharge while ensuring adequate
      nutrition. Multiple regression analysis was used to determine the relationship
      between energy requirement and body weight, percent burn, and age. RESULTS: An
      additional 30% of MREE provided a consistent ratio of actual energy intake to
      required intake. MREE x 1.3 was used as a guide to study the existing
      calculations. For both groups, the four equations that predicted energy in
      healthy children most often underestimated MREE x 1.3, whereas the five formulas
      for children with burns tended to overpredict energy. Regression analysis yielded
      two new sets of equations using age, preburn weight, and percent burn (< 3 years
      = Mayes 1 [r2 = .71], 5 to 10 years = Mayes 3 [r2 = 70] or percent third-degree
      burn (< 3 years = Mayes 2 [r2 = .68], 5 to 10 years = Mayes 4 [r2 = .67]).
      CONCLUSIONS: The application of a 30% factor to MREE is supported in burn
      patients younger than 10 years of age. Standard energy projections do not provide
      an accurate assessment of energy needs in the pediatric burn population; thus,
      two sets of equations that more closely predict energy needs are proposed.

PMID- 8537567
TI  - Residence of college students affects dietary intake, physical activity, and
      serum lipid levels.
AB  - OBJECTIVE: Dietary intake, physical activity, and serum lipid levels of college
      students living on and off campus were compared. DESIGN: Subjects completed a
      questionnaire regarding lifestyle factors and a 3-day food record. Lipid levels
      were determined. SUBJECTS: College students enrolled in an introductory nutrition
      class. MAIN OUTCOME MEASURES: Energy and nutrient intakes and serum lipid levels.
      STATISTICAL ANALYSES PERFORMED: Analysis of variance and Student's t tests were
      used to determine differences in energy and nutrient intakes and serum lipid
      levels between men and women living on and off campus; chi 2 analysis was used to
      determine whether there were associations between residence and lifestyle
      factors; stepwise multiple regression analysis was used to investigate
      relationships among serum lipid levels, nutrient intakes, and exercise levels.
      RESULTS: Of the 104 participants, 81% were women and 19% were men; 51% lived on
      campus. In women, there was a statistically significant difference in age based
      on residence. Reported percentage of energy from protein was significantly higher
      in subjects living off campus. Serum triglyceride level and the ratio of total
      cholesterol to high-density lipoprotein were also significantly higher in
      students living off campus. APPLICATIONS/CONCLUSIONS: Residence may affect serum
      lipid levels; living arrangements influence lifestyle factors such as food
      choices, nutrient content of the diet, and activity patterns. University
      foodservice directors are challenged to offer low-fat foods that students will
      choose to eat. Nutrition education is important for all students because their
      lifestyle may predispose them to development of chronic disease.

PMID- 8537568
TI  - Transformational leadership of clinical nutrition managers.
AB  - OBJECTIVE: To identify leadership qualities of clinical nutrition managers and
      associate these leadership qualities with selected demographic variables (eg,
      training/degree, length of time in management, number of people supervised,
      income, and participation in advanced practice activities). DESIGN: The theory of
      transformational leadership, that is, leadership that incorporates specific
      interpersonal behaviors of the leader and his or her actions within the
      organization, provided the framework for the study. Specific transformational
      leadership qualities--leader behavior, leader personal characteristics, and the
      effect of the leader on organizational functioning and culture--were measured
      using the Leadership Behavior Questionnaire (LBQ). The reliability and validity
      of the LBQ have been reported previously. Other data were obtained using two
      demographic surveys. SAMPLE: Demographic surveys were mailed to 1,599 members of
      the Clinical Nutrition Management dietetic practice group. From the 951 (59.8%)
      respondents, a study sample of 150 clinical nutrition managers and their
      subordinates was selected to receive the LBQ; 116 (77.3%) instrument sets were
      used for analysis. STATISTICAL ANALYSIS: Descriptive statistics were used to
      analyze the demographic surveys. A specified mixed linear model repeated measures
      Statistical Analysis System procedure was used to compare the clinical manager
      and subordinate LBQ scores. Association of the selected demographic variables
      with leadership qualities was measured by lambda, a predictive value measure,
      using the BMDP 4F program. RESULTS: Clinical nutrition managers exhibited
      transformational leadership qualities as rated by the LBQ, rating lowest on the
      communication leadership score and highest on the respectful leadership score.
      Most of the clinical nutrition manager self LBQ scores were significantly higher
      than the clinical nutrition manager LBQ scores rated by subordinates. The
      selected demographic variables appeared to have the strongest predictive effect
      for the visionary culture building subscore of the LBQ. The visionary culture
      building subscore is a measure of how well the leader interacts with and affects
      the functioning of an organization. APPLICATIONS/CONCLUSIONS: More research is
      needed to define leadership in dietetics: this study can serve as a possible
      model. One way clinical nutrition managers may be able to enhance their
      leadership behaviors is to strengthen their skills in communicating their vision.
      Programs are needed to help clinical nutrition managers shape their organizations
      to foster leadership development in their subordinates.

PMID- 8537569
TI  - Maternal intake of cruciferous vegetables and other foods and colic symptoms in
      exclusively breast-fed infants.
AB  - OBJECTIVE: We sought to assess relationships among components of maternal diet
      and the presence of colic symptoms among exclusively breast-fed infants aged < or
      = 4 months. DESIGN: Data were collected by means of a mailed questionnaire that
      solicited information on the presence of symptoms of colic in infants and
      maternal intake of 15 foods (including four cruciferous vegetables) during the
      week before completion of the questionnaire. SUBJECTS: Exclusively breast-feeding
      women (n = 272) and their 273 infants aged < or = 4 months. STATISTICAL ANALYSES
      PERFORMED: Dietary variables were analyzed categorically by logistic regression.
      Two-by-two tables were used to calculate relative risks. RESULTS: Relative risks
      (RRs) and 95% confidence intervals (CIs) for colic symptoms by food items the
      mothers consumed ranged from 0.7 (CI = 0.3 to 1.5) for beef to 2.0 (CI = 1.1 to
      3.5) for cow's milk. Maternal intake of cabbage (RR = 1.3, CI = 1.1 to 1.5),
      cauliflower (RR = 1.2, CI = 1.0 to 1.4), broccoli (RR = 1.3, CI = 1.0 to 2.2),
      cow's milk (RR = 2.0, CI = 1.1 to 3.5), onion (RR = 1.7, CI = 1.1 to 2.5), and
      chocolate (RR = 1.5, CI = 1.0 to 2.2) were significantly related to colic
      symptoms. Maternal intake of more than one cruciferous vegetable was associated
      with an RR of 1.6 (CI = 1.1 to 2.4) for infants experiencing one or more colic
      symptoms. CONCLUSION: Results of this study provide initial evidence that
      maternal intake of cruciferous vegetables, cow's milk, onion, or chocolate during
      exclusive breast-feeding is associated with colic symptoms in young infants.

PMID- 8537570
TI  - Indirect calorimetry in critically ill patients: role of the clinical dietitian
      in interpreting results.
AB  - Evaluation and interpretation of energy needs of critically ill patients require
      the expertise of clinical dietitians: Dietitians must be knowledgeable about the
      methods available to quantify energy needs and able to communicate effectively
      with physicians and nurses regarding nutritional requirements. Several prediction
      equations are available for calculating energy needs of critically ill patients.
      Indirect calorimetry is also used frequently to measure energy requirements in
      this patient population. This article defines when energy expenditure measured by
      indirect calorimetry may provide clinically useful information. Data obtained by
      indirect calorimetry must be interpreted carefully. Indirect calorimetry is based
      on the equations for oxidation of carbohydrate, protein, and fat. Errors in
      interpretation can be made when metabolic pathways other than oxidation dominate
      or when clinical conditions exist that affect carbon dioxide excretion from the
      lungs. Before incorporating data obtained from indirect calorimetry into a
      nutrition care plan, the clinical dietitian should carefully evaluate the
      following factors for a patient: clinical conditions when the measurement was
      made, desired weight loss or gain, tolerance to food or nutrition support,
      relationship between protein intake and energy need, and need for anabolism or
      growth. This article provides clinical examples illustrating how measured values
      compare with calculated values and recommendations for how to incorporate
      measured values into nutrition care plans.

PMID- 8537571
TI  - Binge eating among the overweight population: a serious and prevalent problem.
AB  - Obesity is a major public health problem in the United States and is now
      recognized as a heterogeneous condition. This suggests that treatment
      effectiveness may be improved with an increased understanding of the multiple
      factors contributing to obesity. Recent data clearly indicate that one common and
      serious factor among a subset of the overweight population is binge eating.
      Dietitians in research settings, clinical settings, or private practice are
      likely to treat obese patients who are seeking weight-related treatment. This
      article provides an overview of current knowledge about obese persons who binge
      eat and recommends that dietitians who treat patients for weight-related
      conditions take a proactive role by screening them for binge eating problems or,
      at a minimum, screen those who are suspected of binge eating and then refine
      treatment approaches accordingly.

PMID- 8537572
TI  - Change in eating attitudes: an outcome measure of patients with eating disorders.

PMID- 8537573
TI  - Incidence of eating disorders among selected female university students.

PMID- 8537574
TI  - Satiety level does not affect reporting of energy intake as assessed by a food
      frequency questionnaire.

PMID- 8537575
TI  - Three-Factor Eating Questionnaire and Eating Disorder Inventory in the evaluation
      of psychological traits and emotional reactivity in obese patients.

PMID- 8537576
TI  - Position of the American Dietetic Association: food irradiation.

PMID- 8537577
TI  - Position of the American Dietetic Association: vitamin and mineral
      supplementation.

PMID- 8537578
TI  - Do older women use estrogen replacement? Data from the Duke Established
      Populations for Epidemiologic Studies of the Elderly (EPESE)
AB  - OBJECTIVES: The primary purpose of this study was to determine the prevalence of
      current and past estrogen use among older, community-dwelling, postmenopausal
      women. The secondary purpose was to describe factors associated with estrogen use
      in this population. DESIGN: A survey. SETTING: The Piedmont region of North
      Carolina. PARTICIPANTS: The sample included 2602 community-dwelling women over
      the age of 65 who were interviewed for the Duke Established Populations for
      Epidemiologic Studies of the Elderly (EPESE). MEASUREMENTS: Current and past use
      of estrogen. RESULTS: Of the women surveyed, 6.1% reported current estrogen use,
      and 18.5% reported past use. Approximately half of the participants reported
      using estrogen for more than 2 years. Multivariate analysis demonstrated that
      current estrogen users were younger, more affluent, had smaller families, and
      were more likely to be white and to live in an urban area than were never users.
      Current users were also more likely to drink alcohol and to take calcium
      supplements; and compared with past estrogen users, they were more likely to be
      white, have smaller families, and to drink alcohol. CONCLUSION: Estrogen
      replacement therapy is used by a small minority of older women, especially
      blacks. Moreover, although women with some risk factors for osteoporosis are more
      likely to use estrogen, the chief determinants of estrogen utilization are
      socioeconomic.

PMID- 8537579
TI  - CPR survival of older nursing home patients.

PMID- 8537580
TI  - Association between elevated body-mass index and impaired sense of smell in older
      people.

PMID- 8537581
TI  - Hypertensive encephalopathy in an old man.

PMID- 8537582
TI  - Tinnitus as the first clinical manifestation of hydrocephalus.

PMID- 8537583
TI  - Respiratory muscle weakness in primary hyperparathyroidism.

PMID- 8537584
TI  - Vivre ou laisser mourir.

PMID- 8537585
TI  - The relationship of joint symptoms with exercise performance in older adults.
AB  - OBJECTIVES: The objective of this study is to determine if exercise increases
      joint symptoms in older adults with a history of arthritis or produces symptoms
      in older adults without such history. In addition, we examine whether joint
      symptoms explain the large observed variation in strength gain in older adults
      undergoing vigorous strength training exercise, and report the incidence of
      musculoskeletal injuries upon initiation of an exercise program. DESIGN: A
      population-based, single blinded, randomized controlled trial with three exercise
      groups and one control group. SETTING: A large urban health maintenance
      organization. PARTICIPANTS: Older men and women (N = 105) aged 68 to 85, with leg
      strength below the 50th percentile for their age, sex, height, and weight and
      without neuromuscular disease or active cardiovascular disease. INTERVENTIONS:
      Supervised exercise in 1-hour sessions, three times each week, for 24 to 26
      weeks. One exercise group did strength training (ST) using weight machines (n =
      25); another group did endurance training (ET) using stationary cycles (n = 25);
      and the third group did combined strength training and endurance training (ST+ET)
      (n = 25). The control group (n = 30) received no intervention. MEASUREMENTS:
      Strength was measured at the ankle, knee, hip, and elbow using an isokinetic
      dynamometer. Joint symptoms were rated on a 6-point scale (0 = none, 5 = severe).
      Arthritis severity was based on self-reported use of arthritis medication. Health
      status was measured with subscales of the SF-36 and Sickness Impact Profile
      (SIP). RESULTS: Joint symptoms fluctuated over time in all exercise groups, but
      they did not improve or worsen significantly in any group. The physical dimension
      of the SIP and SF-36 subscale scores, including Bodily Pain Scores, did not
      change over time in any group. Subjects with arthritis and joint symptoms gained
      as much strength with strength training as did subjects without joint symptoms.
      Adjustment for age, gender, baseline strength, adherence, and exercise group did
      not affect this finding. The rate of minor musculoskeletal injuries was 2.2
      injuries per 1000 exercise hours. CONCLUSIONS: Moderate intensity stationary
      cycle exercise and vigorous intensity strength training do not appear to produce
      or exacerbate joint symptoms in older adults. Joint symptoms did not explain the
      large variation in gains in strength in older adults participating in a
      standardized strength training exercise program. Musculoskeletal injuries
      occurred relatively infrequently, and no major injuries occurred. In evaluating
      joint pain that occurs in older adults in well regulated exercise programs,
      clinicians should consider other etiologies before attributing pain to exercise
      per se.

PMID- 8537586
TI  - Multi-site study of incidence of pressure ulcers and the relationship between
      risk level, demographic characteristics, diagnoses, and prescription of
      preventive interventions.
AB  - OBJECTIVE: To determine the incidence of pressure ulcers in varied populations,
      and whether demographic characteristics (age, gender, race) and primary diagnosis
      are factors in pressure ulcer development when the level of risk for developing
      ulcers is considered. To determine if there is a difference in the type of
      preventive services prescribed for persons who do or do not develop pressure
      ulcers when risk is controlled and whether differences can be related to
      demographic characteristics. DESIGN: Cohort study. SETTING: Two skilled nursing
      homes, two university operated tertiary care hospitals, and two Veteran's
      Administration Medical Centers (VAMCs) in Omaha, NE, Durham, NC, and Chicago, IL.
      PATIENTS: A total of 843 randomly selected patients more than 19 years of age who
      did not have pressure ulcers on admission to their place of care. Subjects were
      63% male, 79% white, and had a mean age of 63 (+/- 16) years. MEASURES: A head-to
      toe skin assessment for pressure ulcers recording site and stage of ulcers,
      scores for the Braden Scale for Predicting Pressure Sore Risk, demographic
      characteristics (age, sex, race), and primary diagnosis and preventive
      interventions (turning or repositioning orders and pressure reduction surface)
      were documented on the patient record. Observations were made every 48 to 72
      hours for a minimum of 1 to a maximum of 4 weeks. MAIN OUTCOME MEASURES:
      Presence/absence and stage of pressure ulcers. MAIN RESULTS: One hundred eight of
      843 (12.8%) subjects developed pressure ulcers. The incidence was 8.5%, 7.4%, and
      23.9% in tertiary care, VAMCs, and nursing homes, respectively. Logistic
      regression demonstrated that lower Braden Scale scores, older age and white race
      predicted pressure ulcers; gender was not predictive. Primary diagnoses were not
      significant predictors of pressure ulcer risk when the Braden Scale score was
      entered into the regression. Prescription of turning was predicted by Braden
      Scale scores and by white race, whereas prescription of pressure reduction was
      predicted by Braden Scale scores, white race, and female sex. CONCLUSIONS: Risk
      assessment, rather than diagnoses or demographic characteristics, is recommended
      as the basis for prescriptive decisions. Risk assessment should cue health care
      providers to make more judicious use of turning and support surfaces to prevent
      pressure ulcers. Persons who are at risk for pressure ulcers should have turning
      and pressure reduction surfaces consistently prescribed and implemented. The
      costs and goals of preventive prescription for those not at risk for pressure
      ulcers should be considered.

PMID- 8537587
TI  - Declining cholesterol and mortality in a sample of older nursing home residents.
AB  - OBJECTIVE: To examine the association between declining serum cholesterol and
      mortality in a sample of older nursing home residents. DESIGN: A retrospective
      cohort study. SETTING: A 203-bed nursing home. PARTICIPANTS: Persons aged 65 and
      older, resident in the nursing home on January 1, 1988, or admitted through
      December 31, 1989, were eligible (n = 185) for the study. Follow-up for mortality
      was conducted until June 30, 1991. Fifty-five survivors with two or more
      cholesterol levels recorded before January 1, 1990, and the 76 decedents with two
      or more recorded cholesterol levels constituted the analytic sample (71% of
      eligible subjects). OUTCOME MEASURE: Mortality of the nursing home residents.
      RESULTS: Cholesterol declined 31.1 mg/dL/yr (95% confidence interval [CI], 19.7
      to 42.6) among decedents, versus 4.2 mg/dL/yr (95% CI, -4.9 to 13.2) among
      survivors. The association between cholesterol decline (absolute or relative
      rates) and mortality was examined using logistic regression controlling for age,
      sex, and tube feeding. Compared with a referrent group with no change or
      increase, declining cholesterol greater than 45 mg/dL/yr was accompanied by an
      adjusted relative odds for death of 6.2 (95% CI, 2.1 to 18.4); declining
      cholesterol greater than 20% per year was accompanied by an adjusted relative
      odds for death of 7.3 (95% CI; 2.4 to 22.2). Extreme declines greater than 20%
      per year occurred in 47% of decedents but in only 15% of survivors. CONCLUSION:
      Precipitously declining cholesterol appeared to be a marker for mortality in the
      sample and may help explain the low cholesterol-mortality association in older
      nursing home residents.

PMID- 8537588
TI  - Enhancement of proxy appointment for older persons: physician counselling in the
      ambulatory setting.
AB  - OBJECTIVE: To determine the effectiveness of physician-initiated counselling on
      the rate of health care proxy appointment. DESIGN: Observational study of an
      intervention in a convenience sample. SETTING: A geriatric outpatient clinic in a
      tertiary care teaching hospital, New York, New York. PARTICIPANTS: A total of 687
      patients enrolled in the geriatric clinic during the study period March 1991
      through June 1993. INTERVENTION: Physician counselling about the New York State
      Health Care Proxy Law, distribution of educational materials and healthcare proxy
      forms, and reminders in 331 of 466 eligible patients. MEASUREMENTS: Rate of
      healthcare proxy appointment in eligible and counselled groups; predictors of
      appointment and non-appointment; time elapsed from counselling to appointment;
      reasons for non-appointment; characteristics of the proxy appointment process.
      RESULTS: A healthcare proxy was appointed for 31.5% of patients eligible for
      counselling and for 44% of patients who actually received the intervention,
      compared with a 2.3% proxy appointment rate at baseline. Eighty-one percent of
      the patients completing the proxy appointment process did so at or before their
      third clinic return visit after the counselling intervention. Of the counselled
      patients who did not appoint a proxy, 25% explicitly declined, and 75% had not
      come to a decision by the end of the study period. Proxy completion was
      associated with ethnicity, education, and more frequent clinic visits. Of those
      who appointed a proxy, 97% had good or fair comprehension of the procedure, 92%
      discussed the appointment with their designees, 63% appointed a daughter or son,
      and 80% discussed their wishes for care at the end of life with their proxy.
      CONCLUSIONS: Physician counselling of older outpatients is an effective means of
      increasing healthcare proxy appointments.

PMID- 8537589
TI  - Memory complaints and memory impairment in older individuals.
AB  - OBJECTIVE: To examine whether subjective memory complaints, measured with a
      series of four questions, are associated with performance on cognitive tests.
      DESIGN: Cross-sectional study of individuals, 65 to 85 years of age, who lived in
      the community of Amsterdam. PARTICIPANTS: Individuals were selected randomly
      within 5-year age strata from the patient lists of 30 general practitioners. Of
      the 4051 participants, 2537 nondepressed and nondemented respondents were
      included in the analysis. MEASURES: Four categories of subjective memory
      complaints were developed on the basis of answers to questions about the presence
      or absence of memory complaints and memory-related problems in daily functioning.
      Tests of cognitive function were derived from the subscales of the CAMCOG. MAIN
      RESULTS: Individuals with complaints and memory-related problems performed more
      poorly on tests of memory and memory-related functions. This relationship was
      strengthened after adjusting for age, sex, and premorbid verbal intelligence, all
      of which were related to complaint status and to performance on cognitive tests.
      CONCLUSION: Simple questions about memory function are related to memory
      performance in nondepressed, nondemented community-dwelling older people.
      Subjective memory complaints may be a promising indicator of memory impairment
      that signals the need for follow-up.

PMID- 8537590
TI  - Differences in the signs and symptoms of hyperthyroidism in older and younger
      patients.
AB  - OBJECTIVES: To determine if aging modifies the clinical presentation of
      hyperthyroidism and the signs of thyrotoxicosis in older people. DESIGN:
      Prospective cohort study. SETTING: A French university hospital. SUBJECTS: Eighty
      four new patients with overt hyperthyroidism confirmed chemically between January
      1992 and January 1993. Controls were 68 older euthyroid patients matched to the
      older hyperthyroid patients. MEASUREMENTS: Comparison of 19 classical signs of
      hyperthyroidism between 34 older patients (> or = 70 years; mean age 80.2) and 50
      younger patients (< or = 50 years; mean age 37.4). Older patients were also
      compared with controls (mean age 81.3). RESULTS: Three signs were found in more
      than 50% of older patients: tachycardia, fatigue, and weight loss. Seven signs
      were found significantly less frequently in older patients (P < .001):
      hyperactive reflexes, increased sweating, heat intolerance, tremor, nervousness,
      polydipsia, and increased appetite. Only anorexia (32% vs 4%) and atrial
      fibrillation (35% vs 2%) were more found frequently in older people (P < .001). A
      goiter was present in 94% of the younger and in 50% of the older patients (P <
      .001). The mean number of clinical signs found in the older subjects was
      significantly smaller than the number found in younger patients (6 vs 10.8; P <
      .001). Comparison with older controls showed three signs that were highly
      associated with thyrotoxicosis in older people: apathy (Odd ratio (OR): 14.8),
      tachycardia (OR: 11.2), and weight loss (OR: 8.7). CONCLUSION: This study
      confirms the paucity of clinical signs of hyperthyroidism in older adults. These
      results suggest the necessity of routine screening for thyroid disease in this
      age group.

PMID- 8537591
TI  - Use of cardiovascular drugs in an older Swedish population.
AB  - OBJECTIVE: To describe the use of cardiovascular drugs in an older population
      with respect to age, sex, housing type, and creatinine clearance. DESIGN: A cross
      sectional survey. PARTICIPANTS: All residents of a district of Stockholm
      (Kungsholmen), Sweden, aged 75 and older, living in institutions or at home.
      MEASUREMENTS: Cardiovascular drug use, serum creatinine, electrolytes, height,
      weight, and symptoms. RESULTS: A total of 43 cardiovascular (CV) drugs were used.
      The most common drugs were digoxin (used by 18.2%), furosemide (16.4%), and
      glyceryl trinitrate (12.4%). Drugs with an antihypertensive effect accounted for
      61% of all CV drugs. CV drug use increased with age for cardiac glycosides and
      diuretics, but decreased with age for calcium antagonists and beta-blockers. Drug
      doses tended to be less than the recommended daily dose except for a few drugs,
      e.g., furosemide. There was a trend toward decreasing dose with increasing age,
      but this was not significant. Diuretics were the only CV drugs used more often in
      women. People living in institutional care used the least amount of CV drugs. The
      dose of drugs taken did not appear to be related to estimated creatinine
      clearance. Comparisons between drug use and complaint of symptoms showed a strong
      correlation between the use of cardiac glycosides and anorexia, calcium
      antagonists and constipation, and nitrates and vertigo. There were weaker
      correlations with cardiac glycosides and visual disturbances and with potassium
      sparing diuretics and a high potassium. CONCLUSIONS: CV drugs are used commonly
      in older people. We suggest that the symptoms correlating with cardiac glycoside
      use may be signs of unrecognized toxicity, and this may relate to our finding
      that drug use is often not tailored to renal function as measured by creatinine
      clearance.

PMID- 8537592
TI  - Occurrence of fibroadenomas in postmenopausal women referred for breast biopsy.
AB  - OBJECTIVE: To examine the occurrence of breast fibroadenomas in postmenopausal
      patients referred for breast biopsy. DESIGN: A retrospective review of breast
      biopsy outcome and of patient demographics, including menstrual and hormonal
      status. SETTING: The Tucson Breast Center, a large outpatient breast cancer
      detection clinic affiliated with the University of Arizona Health Sciences Center
      in Tucson, Arizona. PARTICIPANTS: All women seen at the Tucson Breast Center
      between 1985 and 1990 who were referred for breast biopsy. RESULTS: A total of
      100 fibroadenomas were found in 709 breast biopsies whose results were known.
      Fifty-two of these were in premenopausal women and 44 in postmenopausal women;
      the menopausal status of four women was unknown. In postmenopausal women, 11 of
      the 44 patients reported hormone use. Fibroadenomas constituted 20% (39 of 195)
      of the benign masses and 12% (39 of 339) of all breast masses in postmenopausal
      women. Fibroadenomas constituted 10% (44 of 447) of all biopsies in
      postmenopausal women, including those with breast masses, abnormal
      calcifications, or other lesions. CONCLUSION: Noncalcified fibroadenomas of the
      breast are not confined to young women and may constitute a small but noteworthy
      proportion of lesions coming to breast biopsy in postmenopausal women.

PMID- 8537593
TI  - Reporting mistreatment of older adults: the role of physicians.
AB  - OBJECTIVE: To characterize elder mistreatment reporting patterns over time and by
      reporting source with specific focus on physician reporting. To determine whether
      demographic or socioeconomic factors influenced the reporting of elder abuse in
      Michigan between 1989 and 1993 and whether these factors affected physician
      reporting rates. DESIGN: Analysis of the State of Michigan's records of reported
      cases of suspected adult abuse for the years 1989-1993. MEASUREMENTS: Counties
      were categorized by size, urbanization, and average income. The study population
      was analyzed as four age groups: 18-64, 65-74, 75-84, and 85-99. Physician to
      population ratios were calculated for the county types and compared with
      physician reporting rates. MAIN RESULTS: A total of 27,371 cases of possible
      abuse were reported, 17,238 in persons older than age 65. Physicians reported
      only 2% of cases, and physician reporting rates did not increase over the 5-year
      period. Physician reporting rates were highest in small counties with low
      physician to population ratios. There was a high percentage of primary care
      physicians in these counties. Forty-seven percent of all reported cases were
      substantiated. There was no difference in substantiation rate for physician
      reported cases compared with other professional reporting sources. CONCLUSION:
      Physician reports average only 2% of all reports of suspected elder mistreatment.
      Primary care physicians in counties with low physician to population ratios
      appear to be more active in reporting mistreatment of older people. Increasing
      physician awareness of the problem of elder mistreatment and providing physicians
      with the tools to screen for mistreatment should increase the number of cases
      that are reported to the agencies responsible for assisting mistreated older
      people.

PMID- 8537594
TI  - A randomized trial of dementia care in nursing homes.
AB  - OBJECTIVE: To evaluate the efficacy of a dementia care program to reduce behavior
      disorders in nursing home patients with dementia. DESIGN: Randomized controlled
      clinical trial with 6-month follow-up. SETTING: A 250-bed community nursing home.
      PATIENTS: The nursing home was screened to identify patients with dementia and
      behavior disorders. A total of 118 patients were eligible for randomization. Of
      these, 89 (75.4%) were randomized, and 81 of these (91.0%) completed the trial.
      INTERVENTION: The A.G.E. dementia care program consisted of Activities,
      Guidelines for psychotropic medications, and Educational rounds. The control
      treatment was usual nursing home care. MEASUREMENTS: Behavior disorders,
      antipsychotic drug and physical restraint use, patient activity levels, and
      cognitive and functional status. RESULTS: After 6 months, 12 of 42 (28.6%)
      intervention patients exhibited behavior disorders compared with 20 of 39 (51.3%)
      controls (OR = 0.38; 95% CI [0.15, 0.95]; P = .037). Controls were more than
      twice as likely to receive antipsychotics (OR = 2.55, 95% CI [0.96, 6.76]; P <
      .056), to be restrained during activity times (OR = 2.98, 95% CI [1.10, 8.04]; P
      < .028), and to be restrained on nursing units (OR = 2.14, 95% CI [0.9, 5.3]; P <
      .10). Intervention patients were much more likely to participate in activities
      (OR = 13.71; 95% CI [4.51, 41.73]; P = .001). CONCLUSIONS: The A.G.E. program
      reduces the prevalence of behavior disorders and the use of antipsychotic drugs
      and restraints. It is practical, feasible, and appears to improve the lives of
      patients with dementia in nursing homes.

PMID- 8537595
TI  - Evaluation of four methods for the diagnosis of respiratory syncytial virus
      infection in older adults.
AB  - OBJECTIVE: To evaluate four methods of rapid diagnosis of respiratory syncytial
      virus (RSV) infection in older adults and to compare sensitivities with serologic
      analysis. DESIGN: Prospective comparative analysis. SETTING: Two adult
      daycenters. PATIENTS: Frail older persons attending the daycenter who developed
      signs or symptoms of acute respiratory illness between the months of December and
      February. MEASUREMENTS: Viral cultures performed by standard technique and
      bedside inoculation: antigen detection by indirect immunofluorescence assay (IFA)
      and Directigen enzyme immunoassay (EIA) on nasal brush samples; serologic
      analysis of acute and convalescent sera using EIA. RESULTS: RSV infection was
      documented by serology in 11 of 54 (20%) subjects during the study period.
      Bedside viral cultures were the most sensitive assay and were positive in 6/9
      infections. Standard viral culture detected 5/11 cases. Both methods of rapid
      antigen detection were found to be insensitive, with 1/11 detected by IFA and
      0/11 detected by EIA. CONCLUSION: Rapid antigen tests for the diagnosis of RSV in
      older persons should be used with caution.

PMID- 8537596
TI  - Approach to fever and infection in the nursing home.
AB  - OBJECTIVE: To summarize current information on the scope, epidemiology, clinical
      manifestations, diagnostic approach, and general management of infectious
      diseases in nursing home residents, as well as the specific treatment of common
      infections occurring in the nursing home setting. DESIGN: Survey and literature
      review of the diagnostic and therapeutic problems of nursing home residents with
      infections. CONCLUSIONS: Older persons residing in nursing homes as well as other
      types of long-term care facilities are at increased risk for infections.
      Moreover, infection is the most frequent reason for patients to be transferred
      from nursing homes to an acute-care facility. The most common infections that are
      acquired in nursing homes are urinary tract infection (cystitis pyelonephritis),
      respiratory infections (pneumonia, bronchitis), and skin/soft tissue infections
      (infected pressure ulcers, cellulitis). Most serious infections in this setting
      are caused by bacteria; however, influenza and other respiratory viruses as well
      as herpes zoster may cause significant morbidity in older nursing home residents.
      Mycobacterium tuberculosis infects nursing home residents at a higher rate than
      it infects older community dwellers. Infections in older nursing home residents
      may manifest clinically, with atypical symptoms and signs, including the absence
      of fever. Rapid diagnostic evaluation and early therapeutic intervention are
      essential for minimizing the high mortality and morbidity associated with
      infections in this older population; most nursing home residents with serious
      infections should be considered for hospitalization.

PMID- 8537597
TI  - An abnormal exercise treadmill test in an asymptomatic older patient.

PMID- 8537598
TI  - Should older women use estrogen replacement?

PMID- 8537599
TI  - Improving long-term care for persons with Alzheimer's disease.

PMID- 8537600
TI  - How clearly do we see our memories?

PMID- 8537601
TI  - Alzheimer's syndrome, not Alzheimer's disease.

PMID- 8537602
TI  - Control of influenza in nursing homes.

PMID- 8537603
TI  - Validating the GDS in a nursing home sample.

PMID- 8537604
TI  - A review on the strategies for the development and application of new anti
      arthritic agents.

PMID- 8537605
TI  - Effects of retinoids on regulatory cellular interactions in primary mixed
      lymphocyte reaction (MLR).
AB  - The effects of two retinoids, all-trans-retinoic acid and 13-cis-retinoic acid on
      murine splenic lymphocyte proliferative response in mixed culture were evaluated.
      In contrast with previously reported absence of retinoic acid (RA) effect on
      mixed lymphocyte reaction (MLR) the conditions for a strong potentiation of
      proliferative response of murine lymphocytes with RA were obtained. Stimulatory
      cells were determined to be the main targets for RA. The data suggest that the RA
      potentiating effect is the result of an increase in stimulator cell
      immunogenicity after their pre-treatment with RA before use in MLR. Optimal
      potentiation by retinoids of proliferative response was found at non-optimal
      conditions of mixed culture.

PMID- 8537606
TI  - Concomitant immunity against tumor development is enhanced by the oral
      administration of a kampo medicine, Hochu-ekki-to (TJ-41: Bu-Zhong-Yi-Qi-Tang).
AB  - The oral administration of a kampo herbal medicine, Hochu-ekki-to (TJ-41: Bu
      Zhong-Yi-Qi-Tang) using a water-supplying bottle resulted in a slight but
      significant inhibition of Meth A growth. The oral administration of TJ-41 with
      gastric gavage significantly enhanced the specific antitumor activity against
      Meth A at rechallenge on day 9. In a tumor-neutralizing assay, the tumor draining
      LN cells of the TJ-41 administered mice showed an antitumor activity against Meth
      A. In a cytolytic assay, the anti-Meth A specific cytolytic T lymphocyte activity
      was not detected in the spleen cells of the Meth A bearing and TJ-41 administered
      mice. The oral administration of TJ-41 enhanced the natural killer (NK) activity
      of the spleen cells in naive mice but could not improve the decreased NK activity
      of spleen cells from the tumor bearing mice. In a cytostatic assay, the
      peritoneal exudate cells from the Meth A bearing and TJ-41 administered mice
      showed a significantly higher amount of cytostatic activity against Meth A than
      that from either Meth A bearing or TJ-41 administered mice. These results
      indicate that the oral administration of TJ-41 into the tumor bearing mice may
      thus be able to enhance concomitant antitumor immunity through the augmentation
      of the cytostatic activity.

PMID- 8537607
TI  - Lipid peroxidation and changes in T lymphocyte subsets and lymphocyte
      proliferative response in experimental iron overload.
AB  - This study was undertaken to investigate the hypothesis that lipid peroxidation
      might be associated with immunological abnormalities in experimental
      hemosiderosis. The correlation between the degree of plasma and spleen lipid
      peroxidation with lymphocyte proliferative response and with the proportion of T
      lymphocyte subsets was studied in normal and iron overloaded male Sprague Dawley
      rats. The iron-loading protocol consisted of a total dose of iron-dextran (1.5
      mg/Kg body weight) divided in daily i.m. injections over twenty consecutive days.
      Lipid peroxidation was measured by the thiobarbituric acid assay in plasma and in
      homogenates of spleen. Plasma lipid peroxide level increased rapidly after i.m.
      administration of iron-dextran and decreased sharply at 48 h after the last
      injection. Conversely, a progressive increase of lipid peroxidation in
      homogenates of spleen was observed in the course of the iron overload protocol,
      remaining high even at 50 days after initiation of iron-dextran injections. The
      increase of spleen lipid peroxide levels was associated with decreased lymphocyte
      proliferative response to Con A in iron overloaded rats. The addition of
      superoxide dismutase and catalase to lymphocyte cultures reversed the inhibition
      of the proliferative response, implicating reactive species of oxygen as the
      causative agents of these alterations. These effects may be related with the
      enhanced membrane and DNA damage occurring during intracellular and extracellular
      peroxidation. Negative correlations between helper/cytotoxic ratio and
      malondialdehyde levels were obtained in blood and spleen during iron
      administration. These results supports the hypothesis that lipid peroxidation
      plays a role in the immunological abnormalities observed in experimental
      hemosiderosis.

PMID- 8537608
TI  - Effect of hepatic isoferritins from iron overloaded rats on lymphocyte
      proliferative response: role of ferritin iron content.
AB  - Iron and ferritin impair a variety of immunological functions. To evaluate the
      effect of ferritin iron content on rat lymphocyte proliferative response,
      isoferritins that differ in their iron content and isoelectric point (pI) were
      isolated from iron overload rat livers by ultracentrifugation (isoferritins with
      high iron content and low pI) or crystallization (isoferritins with low iron
      content and high pI) methods. Additionally, commercial horse splenic ferritin
      (with a lower pI and higher iron content than rat isoferritins) was also tested.
      Proliferative response to Con A was decreased in a dose-dependent manner in all
      assays in which spleen cells were incubated with rat and horse isoferritins.
      However, isoferritins with higher iron contents (rat isoferritin obtained by
      ultracentrifugation and horse ferritin) caused a greater decrease of
      proliferative response at 5 and 25 micrograms/ml than the others. Rat and horse
      apoferritins showed no inhibitory effect on lymphocyte proliferative response,
      suggesting that the effect is due to iron probably through the damaging effect of
      reactive oxygen species generated by iron released by the isoferritins on
      lymphocyte functions. Additionally, the role of serum ferritin level on
      proliferative response was studied in an experimental model of iron overload in
      rats. An inverse relationship between the proliferative response and serum
      ferritin levels was observed. Our results suggest that the inhibitory effect of
      the isoferritins on lymphocyte proliferative response is due, at least partially,
      to the iron content of this protein and not exclusively to variation in pI as
      suggested by other authors. These results are in agreement with the possible
      immunosuppressor role of ferritin in vivo.

PMID- 8537609
TI  - Modulating effect of sodium diethyldithiocarbamate on neutrophils in normal,
      febrile and cold-stressed rabbits.
AB  - The studies were conducted on normal, febrile and cold-stressed rabbits. Fever
      was induced by a single intravenous injection of 1 micrograms/kg of E. coli
      lipopolysaccharide (LPS). The animals were submerged in ice-water for 20 s and
      then were kept at -15 degrees C for approx. 8 min., until their body temperature
      dropped by 3 degrees C. Sodium diethyldithiocarbamate (DTC) was injected i.v. to
      normal, febrile and cold-stressed rabbits, in a single dose of 2 or 20 mg/kg. The
      effect of DTC on body temperature, the number of neutrophils in blood, phagocytic
      activity of neutrophils and their ability to reduce nitroblue tetrazolium (NBT)
      were evaluated. It was found that DTC administered in a dose of 2 or 20 mg/kg did
      not affect the body temperature of rabbits. In normal rabbits, DTC did not change
      the number of neutrophils, but increased their phagocytic activity and ability to
      reduce NBT. In febrile rabbits, DTC depending on the dose, shortened the
      stimulating effect of LPS on neutrophil ability to reduce NBT but enhanced and
      prolonged the effect of pyrogen on neutrophil phagocytic activity. The rabbits
      treated with DTC prior to hypothermia exhibited shorter neutrophilia resulting
      from cold stress. In addition, DTC administered to the rabbits before their
      exposure to cold stress proved to be a partial or even total protection against
      the decrease in NBT reducing ability and phagocytic activity of blood
      neutrophils.

PMID- 8537610
TI  - The effects of methimazole on haematopoiesis in mice.
AB  - The effects of anti-thyroid drug, methimazole (MMI), on haematopoiesis in inbred
      C57BL/6 mice were studied. The in vitro proliferative response of bone marrow
      (BM) cells to interleukin-3 (IL-3) was significantly increased when mice were
      provided with 0.1% MMI in water (w/v) ad librium for 4 to 6 weeks. Using soft
      agar agar colony assay, the numbers of myeloid cell colonies were also
      significantly increased in mice treated with MMI. However, the proliferative
      response of BM cells to IL-3 was found to be greatly reduced 10 weeks after MMI
      treatment. In vitro studies showed that MMI alone at the concentrations of 500
      microM or above inhibited both the growth of normal BM cells in liquid culture
      and the formation of macrophage (M)-/granulocyte (G)-colonies in soft agar
      culture in a dose dependent manner. Direct cytotoxic effect of MMI (0 - 1250
      microM) to normal BM cells was not observed. Results from this study suggested
      that MMI can modulate the development of myeloid haematopoietic cells.

PMID- 8537611
TI  - Modulation of primary antibody response by protein A in tumor bearing mice.
AB  - Protein A (PA) is a cell wall glycoprotein of Staphylococcus aureus Cowan I,
      which possess a number of immunomodulatory and antitumor properties. We have
      previously shown that PA suppresses the anti-sheep erythrocyte primary antibody
      response in normal mice. The present investigation evaluates the effect of
      protein A on the anti-sheep erythrocyte primary antibody response in tumor
      bearing mice. The primary antibody response in tumor-bearing mice immunized with
      sheep red blood cells (SRBC) was suppressed by the intraperitoneal administration
      of PA in a dose-dependent fashion. The plaque forming cell (PFC) assay was used
      to assess this response. Maximum suppression of the PFC response was observed at
      12 micrograms PA/animal (p < 0.001) and could be observed at doses as low as 1
      microgram PA/animal (p < 0.01). The amount of suppression was proportional to the
      number of PA doses administered. In addition this effect was critically dependent
      on the timing of PA administration. PA showed no significant effect on PFC when
      injected after immunization, but it produced pronounced suppression when injected
      prior to the immunization with SRBC. Maximum suppression of the PFC response was
      observed when PA was administered one day before the antigen challenge. PA also
      reduced splenic localization of 51Cr labeled SRBC to 42% (p < 0.01). The altered
      localization of antigen in spleen may be responsible for reduced PFC response in
      tumor-bearing mice. Depletion of B-lymphocyte is reported to exhibit tumor
      inhibition. Therefore, we propose that the suppression of the primary antibody
      response by PA helps in tumor regression by reducing the soluble
      immunosuppressive immune complexes.

PMID- 8537612
TI  - Effect of short-term therapy with ceftizoxime and ceftriaxone on human peripheral
      WBC, serum immunoglobulins and lymphocyte subpopulations.
AB  - Serum immunoglobulins, peripheral white blood cells and lymphocyte subpopulation
      counts of twenty patients who received ceftizoxime and ceftriaxone for
      antimicrobial prophilaxis in surgery were examined in order to obtain a profile
      of the effects of these drugs on humoral and cellular immune system of human. No
      differences in the serum concentrations of IgG, IgM, IgA, peripheral blood
      lymphocytes and lymphocyte subpopulations 24 h and 48 h following the last dose
      of these two drugs were observed.

PMID- 8537613
TI  - Detoxified venom from Crotalus durissus terrificus is devoid of cytotoxic
      activity and induces mitogenesis.
AB  - The venom from the snake Crotalus durissus terrificus was detoxified by stepwise
      incorporation of stable cationic iodine. The venoid, in a dosage equivalent to
      100 LD50 of the lethal venom, was injected in mice without lethal exits. The
      native venom (NAT), or its toxoided (TXD) derivative were incubated in presence
      or absence of mitogens, with human mononuclear (MN), B and T cells, with a pulse
      of [3H]Thymidine. No synergistic or antagonistic effects were observed in the
      combined activity of the mitogens and NAT or TXD. In the direct action of NAT the
      incorporation of radioactivity into MN and T cells diminished with venom increase
      in concentration indicating that the cytotoxicity of the native venom was
      correlated with the amount added. With B cells, the native venom exercised an
      initial mitogenic activity, declining in the higher concentration. On the other
      hand, the TXD showed a consistent effect, increasing the thymidine uptake in a
      manner related to concentration. This stimulation by TXD was observed with all
      groups of cells. The results indicate that, by abolishing direct cytotoxic
      activity with toxoiding of this venom, a derivative that enhances mitogenesis in
      these white cells can be obtained.

PMID- 8537614
TI  - Fusarium proliferatum culture material alters several production and immune
      performance parameters in White Leghorn chickens.
AB  - White Leghorn Cornell K-strain chicks (3 replicates of 16 per pen) were started
      at Day 7 on feed amended with Fusarium proliferatum culture material containing
      fumonisin B1, fumonisin B2, and moniliformin at 61, 10.5, and 42.7 ppm,
      respectively. Observed effects on performance of treated birds included reduced
      feed conversion at 2 wk, and reduced body weight of males and females up to 6 wk
      (P < or = .05). Splenic, thymic, and liver weights, normalized for body weight,
      were reduced (P < or = .05) with no change in bursa of Fabricius. No significant
      changes were observed histologically in the spleen, bursa, kidney, heart, liver,
      cecal tonsils, colon, or tibia. Significant suppression in total Ig and IgG
      levels occurred. Macrophages from treated chicks exhibited a 34% reduction in
      phagocytic activity. Natural killer cell activity was not affected. These
      findings, which showed that Fusarium toxins alter performance and immune end
      points in chickens, imply that chickens exposed to mycotoxins may be more
      susceptible to infectious diseases.

PMID- 8537615
TI  - Ethics and caring: cornerstones of nursing geriatric case management.
AB  - 1. Paternalism, the most frequent ethical concern voiced by both elders and their
      caregivers, is unilateral decision-making not in accord with the client's stated
      wishes or value system. 2. It is common that older people are intimidated by
      professionals and lack the sophistication and vocabulary to express their desires
      in a rational and assertive manner. 3. Often the family's decisions regarding
      client care do not correlate with the patient's choices in the sense that clients
      want to avoid needless pain and suffering and are more accepting than the
      families of the potential outcome of death. 4. Detailing the nursing care plan in
      writing and allowing several days for client/family review and approval lessen
      misunderstanding and dissatisfaction.

PMID- 8537616
TI  - Psychological intervention for older hip fracture patients.
AB  - 1. Although there are sophisticated surgical procedures for hip fracture repair,
      a substantial proportion of patients never return to pre-fracture levels of
      physical function. Factors that influence the recovery of older hip fracture
      patients represent important areas to study in order to more precisely predict
      outcome. 2. Research findings suggest that elevated depressive symptoms and
      cognitive impairment may negatively affect recovery, while mental alertness,
      emotional stability, and social involvement positively affect recovery. Thus, hip
      fracture and its subsequent disability must be studied as a biopsychosocial
      phenomenon, rather than merely as a physiological event. 3. Older hip fracture
      patients may be at higher risk for psychological problems related to the
      traumatic nature of the injury. A comprehensive psychological assessment at
      admission can assist the nursing staff to determine which patients are at higher
      risk for emotional distress.

PMID- 8537617
TI  - Telephone care for elders: physical, psychosocial, and legal aspects.
AB  - 1. Gerontological nurses can use accessible and convenient telephone care to
      provide follow-up services, health counseling, triage and reassurance. 2.
      Attentiveness to sensory impairments and losses; physical ability; interpersonal
      factors, culture, and education level is crucial to effective telephone care. 3.
      Proper documentation is a component of telephone care.

PMID- 8537618
TI  - Mid-life women, eldercare and employment.

PMID- 8537619
TI  - Nursing home placement decisions and post-placement experiences of African
      American and European-American caregivers.
AB  - 1. For nurses to work effectively with families faced with making a nursing home
      placement decision, they need to understand cultural issues of the patients and
      their caregivers. 2. Caregivers spend more time with other family members and in
      social activities following the elder's placement in a nursing home and also have
      improved relationships with the elder. 3. Few differences were observed between
      the African-American and European-American caregivers. Decisions appear to be
      similar regardless of cultural norms.

PMID- 8537620
TI  - Cerumen impaction in the elderly.
AB  - 1. Cerumen impaction is a reversible cause of conduction hearing loss in the
      elderly. 2. Risk factors include ear canal hairs, hearing aids, bony growths
      secondary to osteophyte or osteoma, and a history of impacted cerumen. 3. Cerumen
      removal can cause damage to the external auditory meatus, perforation of the
      tympanic membrane, and/or otitis media. 4. Methods to remove cerumen impactions
      include: ceruminolytic agents, curette methods and lavage method.

PMID- 8537621
TI  - Effect of cerumen on infrared ear temperature measurement.
AB  - This pilot study examined whether the occlusion of one ear canal with cerumen
      affected the usual temperature difference between the ears as measured with an
      infrared thermometer. Ear-based temperature measurements were made in 14 elderly
      nursing home residents before and 3 to 4 days after irrigation to clear cerumen
      from the occluded ear. The presence of cerumen tended to lower the temperature
      reading, with a mean change of -0.24 +/- 0.47 degrees F (-0.13 +/- 0.47 degrees
      C, p = 0.08) and individual differences ranging from -0.9 to 0.4 degrees F (-0.5
      to 0.2 degrees C), 43% of subjects (6/14) had values lower by -0.5 degrees F (
      0.3 degrees C) or more. The advantage of removing impacted cerumen before making
      infrared ear temperature measurements may be offset by the time and inconvenience
      of the irrigation procedure. Improved hearing may be a more important outcome of
      cerumen removal, with secondary benefit for temperature measurement.

PMID- 8537622
TI  - The new 16-towel test pack: is it a challenge to the sterilizer?

PMID- 8537623
TI  - FDA labeling requirements for disinfection of endoscopes: a counterpoint.

PMID- 8537624
TI  - FDA labeling requirements for disinfection of endoscopes: a counterpoint.

PMID- 8537625
TI  - The tools of quality improvement: CQI versus epidemiology.

PMID- 8537626
TI  - Application of CQI tools to the reduction in risk of needlestick injury.
AB  - OBJECTIVE: To reduce the risk of needlestick injuries to laboratory workers.
      DESIGN: Continuous Quality Improvement (CQI) tools were applied to data collected
      on the number of blood gas syringes that arrived in the laboratory with needles
      still attached and to the reasons for these occurrences. SETTING: A clinical
      chemistry department within a 900-bed tertiary referral university teaching
      hospital. PARTICIPANTS: Clinical chemistry laboratory staff and medical staff
      responsible for sending syringes with needles still attached. INTERVENTIONS:
      Changing to a preheparinized blood gas syringe that included a syringe cap within
      the packaging. RESULTS: Fivefold reduction in the number of syringes arriving in
      the laboratory with needles still attached. CONCLUSION: The risk of needlestick
      injury to laboratory workers can be reduced by provision to clinical staff of
      preheparinized blood gas syringes that include a syringe cap within the
      packaging. The techniques to CQI provide powerful tools for the identification,
      solving, and monitoring of safety-related issues within the healthcare
      environment.

PMID- 8537627
TI  - Subclavian hemodialysis catheter infections: a prospective, randomized trial of
      an attachable silver-impregnated cuff for prevention of catheter-related
      infections.
AB  - OBJECTIVE: To determine if an attachable silver-impregnated cuff is effective in
      reducing subclavian hemodialysis catheter-related infections. DESIGN:
      Prospective, randomized, nonblinded study. SETTING: Community teaching hospital.
      PATIENTS: One hundred one acute and chronic renal failure patients requiring
      subclavian venipuncture and catheterization. After randomization, 47 patients
      underwent subclavian catheterization with a silver-impregnated cuff (Ag-CC), and
      54 patients had routine catheter (RC) placements. MEASUREMENTS: Multiple presumed
      predictor variables for catheter-related infections, exit site infection rate,
      bacteremia rates, and semiquantitative cultures of all catheters.

PMID- 8537628
TI  - Developing policies and guidelines.
AB  - Practice guidelines are proliferating in the era of managed care. Hospital
      epidemiologists frequently are asked to author guidelines of infection control.
      The greatest challenge in the process is not writing the guidelines but
      implementing them. This article offers practical advice on which topic to select
      and on how to develop and implement guidelines.

PMID- 8537629
TI  - The Certification Board of Infection Control, Inc.
AB  - The Certification Board of Infection Control, Inc. (CBIC), was created in 1981 by
      the Association for Professionals in Infection Control and Epidemiology, Inc, for
      the sole purpose of developing and administering an examination by which
      competent infection control professionals could become certified. This
      independent, voluntary board is multidisciplinary, representing all levels of
      professionals in the field of infection control, as well as a consumer member.
      CBIC certification is the only recognized certification for infection control
      professionals. Since the first examination was administered in 1983, over 3,000
      persons have attained infection control certification (CIC) status and are
      permitted to use the CIC credential.

PMID- 8537630
TI  - The Association for Professionals in Infection Control and Epidemiology, Inc.
AB  - The Association for Professionals in Infection Control and Epidemiology, Inc.
      (APIC) is a multidisciplinary voluntary international organization with over
      10,000 members. Its purpose is to influence, support, and improve the quality of
      healthcare through the practice and management of infection control and the
      application of epidemiology in all health settings. The organization, which is
      based in Washington, DC, is led by an elected board of members who volunteer
      their time and expertise.

PMID- 8537631
TI  - Rules on HIV testing of source patients.

PMID- 8537632
TI  - Special update on healthcare reform from the White House.

PMID- 8537633
TI  - 42 CFR Part 84: Respiratory protective devices implications for tuberculosis
      protection.

PMID- 8537634
TI  - Multidrug resistance P-glycoprotein monoclonal antibody JSB-1 crossreacts with
      pyruvate carboxylase.
AB  - Multidrug resistance (MDR) is associated with overexpression of a 170 KD plasma
      membrane P-glycoprotein (P-gp), a putative energy-dependent efflux transporter
      that reduces intracellular accumulation of chemotherapeutic agents. For detection
      of P-gp expression in normal and malignant tissues, an MDR1-specific monoclonal
      antibody (MAb) JSB-1 has been used extensively. In this report we show that MAb
      JSB-1 crossreacts with a protein of M(r) approximately 130,000 present in rat
      liver mitochondrial inner membrane/matrix fractions. Peptide mapping and
      microsequencing identify this protein as pyruvate carboxylase (PC), an abundant
      mitochondrial enzyme. MAb JSB-1 also crossreacts with purified PC from bovine
      liver. Under immunoblotting conditions, this crossreactivity is partially
      abolished by pre-incubation of MAb JSB-1 with a 1000-fold molar excess of MAb
      C494 epitope-specific peptide (PNTLEGN), indicating that the epitope of MAb JSB-1
      may either overlap with or be in close proximity to that of MAb C494.
      Immunohistochemical cross-reactivity was also demonstrated in cryosections of
      human skeletal muscle, a tissue known not to express P-gp. MAb JSB-1 strongly
      immunostained Type 1 fibers, the subtype known to contain abundant mitochondria.
      Use of MAb JSB-1 for detection of MDR1 P-gp expression should be approached with
      caution.

PMID- 8537635
TI  - Human osteoclast and giant cell differentiation: the apparent switch from
      nonspecific esterase to tartrate resistant acid phosphatase activity coincides
      with the in situ expression of osteopontin mRNA.
AB  - Animal model and in vitro cultures suggest that osteoclasts and cells of the
      mononuclear phagocyte system share a common precursor. However, the human
      osteoclast precursor has not been positively identified. We attempted to identify
      the precursor in situ by using a number of osteoclast- and macrophage-selective
      markers, together with the expression of osteopontin mRNA, previously shown to be
      abundant in human osteoclasts. Sections of osteophytic bone and a panel of
      inflammatory connective tissues were processed for in situ hybridization; serial
      sections were analyzed for tartrate-resistant acid phosphatase (TRAP) and
      nonspecific esterase (NSE) activity, selective cytochemical markers for the
      osteoclast and cells of the macrophage/monocyte lineage, respectively. The murine
      anti-human osteoclast monoclonal antibodies 23C6 (vitronectin receptor) and C35
      (osteoclast-selective) were used to further identify the osteoclast phenotype. We
      compared osteoclasts, giant cells, and their respective putative mononuclear
      precursors. At resorption sites within osteophytic bone, osteopontin mRNA was
      expressed in osteoclasts and a distinct population of TRAP+, NSE- mononuclear
      cells. Adjacent clusters of mononuclear cells were TRAP- and NSE+ or were active
      for both enzymes; these cells demonstrated variable expression of osteopontin
      mRNA. In the inflammatory connective tissues, abundant macrophage-like cells
      (NSE+/TRAP-) did not express osteopontin mRNA. However, TRAP+ mononuclear cells
      observed among clusters of NSE+ cells did express osteopontin mRNA. At these
      sites, clusters of putative macrophage polykaryons removing fragments of bone
      debris were observed. These giant cells and associated mononuclear cells were NSE
      and distinctly TRAP+, and expressed osteopontin mRNA, C35, and 23C6 (human
      osteoclast) reactivity. Therefore, cells involved in the remodeling (resorption)
      of bone or the removal of bone debris, together with their immediate precursors,
      switch from being NSE+/TRAP- to NSE-/TRAP+ cells that express osteopontin mRNA.
      We propose that the clusters of NSE+/TRAP- mononuclear cells represent the
      immature osteoclast precursor. In support of this, TRAP+/NSE+ cells were
      occasionally observed in both tissues, representing an intermediate stage in
      differentiation. These results further suggest that cells of the mononuclear
      phagocyte lineage within bone and inflammatory connective tissue have the
      potential to differentiate into osteoclasts.

PMID- 8537636
TI  - Persistence of a perinatal cellular phenotype in submandibular glands of adult
      rat.
AB  - In the perinatal submandibular gland (SMG) of the rat, Type I cells secrete
      protein C (89 KD) and Type III cells secrete B1-immunoreactive proteins (20-30
      KD); both cell types secrete protein D (175 KD). After the disappearance of both
      perinatal cell types from the maturing acini, only cells of the intercalated
      ducts (ID) show strong reactivity for the perinatal antigens. In adult ID, light
      and electron microscopic immunocytochemical analysis showed that most cells had
      either C or B1 reactivity, a few had either C and D or B1 and D reactivities, and
      some cells were unreactive for all of the perinatal proteins. Occasional clusters
      of "adult" acini, however, were strongly positive for B1 and for D, and these
      clusters were negative for a typical adult acinar marker, the glutamine/glutamic
      acid-rich proteins (GRP). Also seen in some preparations were a few anomalous
      acini with the histological appearance of sublingual (SLG) acini. These were
      negative for the perinatal and adult submandibular gland marker proteins but
      reactive with an antibody against SLG mucin. We suggest that the B1-positive
      acini in the adult SMG consist of newly differentiated replacement cells that
      have arisen from the ID, and that the anomalous mucous acini are, phenotypically,
      SLG acini that have differentiated within the SMG parenchyma.

PMID- 8537637
TI  - Proliferating cells in human eccrine and apocrine sweat glands.
AB  - Morphological observations of sweat glands showed degenerated debris of secretory
      cells in the secretory lumen in both apocrine and eccrine sweat glands. This
      suggested that dead secretory cells of human eccrine and apocrine sweat glands
      were released into the lumen and replaced by other cells. However, we did not
      know which type of cells replaced lost secretory cells. Therefore, we studied the
      proliferating cells in human eccrine and apocrine sweat glands by labeling S
      phase cells in vitro with 5-bromo-2'-deoxyuridine (BrdUrd) and by immunostaining
      proliferation-associated proliferating cell nuclear antigen (PCNA) with anti-PCNA
      monoclonal antibody. BrdUrd and anti-PCNA antibody labeled a few secretory cells
      in eccrine and apocrine sweat glands, but neither method labeled myoepithelial
      cells. Luminal and peripheral cells of the eccrine and apocrine coiled duct were
      labeled with both BrdUrd and PCNA. However, we could not find any highly
      proliferative germinative cells in coiled ducts. Our results suggest that lost
      secretory cells could be replaced by proliferation of secretory cells themselves
      rather than by proliferation of myoepithelial cells or duct cells.

PMID- 8537638
TI  - Light microscopic autoradiographic study of DNA synthesis in cecal epithelial
      cells of aging mice.
AB  - The localization and activity of DNA synthesis of mouse cecal epithelia from
      prenatal Day 19 embryos to 12-month adults were investigated by light microscopic
      autoradiography after [3H]-thymidine injection in vivo. The cecal epithelial
      labeled cells with [3H]-thymidine were located at the lower half of the crypts,
      and the labeling index (LI) changed with the development of the cecum due to
      aging. A peak in the LI of absorptive cells was found at embryonic Day 19, but it
      decreased strikingly at the first postnatal day and then kept an almost constant
      value until 12 months. The LI of the goblet cells showed the highest value at
      fetal Day 19, decreased gradually with aging from the first postnatal day, and
      completely disappeared from 1 month onwards. The basal granulated cells were
      located only in the base of crypts, and the significant difference of LI was not
      found from embryonic Day 19 through 12-month adult. The results obtained in this
      study suggest that there are some differences of DNA synthesis among different
      kinds of cecal epithelial cells from embryonic stages to postnatal stages as a
      result of aging.

PMID- 8537639
TI  - Measurement of nitric oxide synthase activity in sections of rat liver.
AB  - In the previous communication we described a histochemical method for measuring
      soluble guanylate cyclase (sGC) activity in sections of rat liver. In theory,
      this method could be used to assess nitric oxide synthase (NOS) activity by the
      increased sGC activity induced by the additional presence of the substrates for
      NOS activity. We found that this was correct provided that the concentration of
      the colloid stabilizer in the reaction medium was decreased to just below the
      concentration required to fully stabilize the guanylate cyclase activity in the
      sections. This was related to the fact that the site of NOS activity was
      different from that of the sGC activity in the hepatocytes, so that the NO
      generated had to diffuse from the Kupffer cells to the hepatocytes as could occur
      only in partially unstabilized sections. Optimal concentrations of arginine and
      of NADPH have been determined for demonstrating NOS activity; the increased
      reaction was shown to be largely inhibited by methyl-arginine.

PMID- 8537640
TI  - Histochemistry of guanylate cyclase activity.
AB  - Guanylate cyclase liberates pyrophosphate from guanosine triphosphate (GTP). In
      studies published previously, this phosphate is trapped by lead ions even though
      it is known that free lead ions inactivate a considerable proportion of this
      enzymatic activity. To overcome the damaging effects of fixation, this study used
      fresh cryostat sections stabilized with a sufficient concentration of a collagen
      derived polypeptide to ensure no measurable loss of guanylate cyclase activity.
      To avoid the damaging influence of free lead ions, we used a hidden metal capture
      reagent, i.e., a complex of lead ammonium citrate/acetate that does not react
      with GTP but which rapidly forms a precipitate with the pyrophosphate liberated
      by the enzyme. The lead precipitate is then converted into the colored sulfide
      which is measured in individual cells by microdensitometry. This system was used
      to measure guanylate cyclase activity in individual cells in unfixed sections of
      rat liver.

PMID- 8537641
TI  - Expression of histidine decarboxylase and cellular histamine-like
      immunoreactivity in rat embryogenesis.
AB  - In this study we investigated the developmental expression of histidine
      decarboxylase (HDC) mRNA and the distribution of histamine-immunoreactive
      (histamine-ir) cells in the rat embryonic tissues. We applied Northern blot
      analysis, in situ hybridization with synthetic oligonucleotide probes
      complementary to the rat HDC cDNA, and indirect histamine immunocytochemistry.
      Northern blot analysis revealed the appearance of a major (2.6 KB) HDC mRNA
      species in liver on embryonic Day 14. Its hybridization level peaked on Day E18,
      when two minor (1.6 and 3.5 KB) mRNA species were also present. During the
      periparturition period, a rapid decrease in HDC RNA was apparent, as the 2.6 KB
      mRNA species was expressed at a low level on postnatal Day P1. The embryonic
      liver expressed HDC on days E14-E20. On days E18 and E20, the periosteum and the
      epiphyseal growth plates of the endochondrally ossificating bones, and some
      striated muscle cells, showed hybridization signal for HDC. Histamine
      immunoreactivity was detected in many epithelial and neuronal cell types during
      embryogenesis. An intense histamine immunoreaction appeared first in essentially
      all cells of the liver parenchyma on day E12. This parenchymal histamine
      immunoreactivity disappeared by birth, after which this immunofluorescence in
      liver was restricted to a few scattered mast cells until adulthood. Some neurons
      in the peripheral sensory, sympathetic and cranial nerve ganglia were histamine
      immunoreactive from day E16 to birth. In addition, many immunoreactive nerve
      fibers were detected in the gastrointestinal muscularis externa, mesentery,
      salivary glands, kidney, lung, and muscle tissue. We conclude that during rat
      embryogenesis histamine is produced and stored transiently by cells in liver,
      developing bone, and a few striated muscle cells, in addition to previously
      reported neurons in rat brain. Many peripheral neurons, epithelial cells, and
      mast cells display histamine immunoreactivity during rat embryogenesis but are
      devoid of detectable HDC mRNA with the current method. It remains possible that
      histamine is formed by another enzyme or is taken up from the extracellular
      space. The results support the concept that a significant proportion of histamine
      is formed and stored by embryonic cells other than mast cells.

PMID- 8537642
TI  - Immunocytochemical localization of catalase in the central nervous system of the
      rat.
AB  - Catalase is a marker for peroxisomes, which are ubiquitous cytoplasmic
      organelles. Although the distribution and features of peroxisomes are well known
      in liver and kidney, these organelles have been rarely studied in neural tissues.
      Catalase is an important scavenging enzyme against reactive oxygen species, as it
      removes H2O2 produced during metabolic processes. Reactive oxygen species are
      involved in a number of brain lesions and in brain aging. We investigated the
      distribution of catalase in rat central nervous system by means of a newly
      developed immunocytochemical procedure for signal enhancement, using an affinity
      purified polyclonal antiserum. The data show that catalase immunoreactivity is
      present in all neural cells, both neuronal and glial, albeit at different
      concentrations. Among glial cells, ependymal cells and tanycytes of the third
      ventricle and the median eminence show the most intense immunoreaction;
      positivity is also found in oligodendrocytes and astrocytes. In general, neurons
      in the brainstem are relatively more immunoreactive than those in the forebrain
      although, within these respective brain regions, there are areas with low and
      high staining intensity. Moreover, within the same area, certain types of neuron
      appear more immunoreactive than others. The cell bodies in the septal nuclei,
      pallidum, reticular thalamic nucleus, mesencephalic nucleus of the trigeminal
      nerve, Deiter's nucleus, locus ceruleus, cranial and spinal motor nuclei, and the
      Golgi cells of the cerebellar cortex are among the most densely stained neurons.
      Catalase immunoreactivity of the cell bodies, which presumably is proportional to
      catalase content, appears to be only partially correlated with cell size or type
      of neurotransmitter used in the nerve endings; it is likely that other unknown
      parameters regulate the abundance of the enzyme. In many cases, highly
      immunoreactive cells correspond to neurons known to be resistant to ischemia
      reperfusion injury, whereas weakly stained cells correspond to neurons that are
      more susceptible to ischemic damage. The amount of catalase may be critical for a
      protective effect against oxidative stress under pathological conditions, such as
      ischemia-reperfusion injury.

PMID- 8537643
TI  - Changes of MAP2 phosphorylation during brain development.
AB  - The microtubule-associated protein MAP2 is essential for development of early
      neuronal morphology and maintenance of adult neuronal morphology. Several splice
      variants exist, MAP2a-d, with a lack of MAP2a in cat brain. MAP2 is widely used
      as a neuronal marker. In this study we compared five monoclonal antibodies (MAbs)
      against MAP2. They show differences in the immunocytochemical distribution of
      MAP2 isoforms during development of the visual cortex and cerebellum of the cat.
      Local and temporal differences were seen with MAb AP18, an antibody directed
      against a phosphorylation-dependent epitope near the N-terminal end. In large
      pyramidal dendrites in visual cortex, the AP18 epitope remained in parts
      immunoreactive after treatment with alkaline phosphatase. Three MAbs, AP14, MT
      01, and MT-02, recognized the central region of the MAP2b molecule, which is not
      present in MAP2c and 2d, and reacted with phosphorylation-independent epitopes.
      During the first postnatal week the immunostaining in cerebellum differed between
      antibodies in that some cellular elements in external and internal granular
      layers and Purkinje cells were stained to various degrees, whereas at later
      stages staining patterns were similar. At early stages, antibody MT-02 stained
      cell bodies and dendrites in cerebral cortex and cerebellum. With progressing
      maturation, immunoreactivity became restricted to distal parts of apical
      dendrites of pyramidal cells and was absent from perikarya and finer proximal
      dendrites in cortex. MT-02 did not stain MAP2 in cerebellum of adult animals.
      This study demonstrates that the immunocytochemical detection of MAP2 depends on
      modifications such as phosphorylation and conformational changes of the molecule,
      and that MAP2 staining patterns differ between MAbs. Phosphorylation and specific
      conformations in the molecule may be essential for modulating function and
      molecular stability of MAP2, and monoclonal antibodies against such sites may
      provide tools for studying the functional role of modifications.

PMID- 8537644
TI  - Efficient immunodetection of various protein antigens in glutaraldehyde-fixed
      brain tissue.
AB  - Optimal ultrastructural preservation of brain tissue for electron microscopy is
      best achieved with fixatives containing high concentrations of glutaraldehyde,
      which is generally considered detrimental to the immunogenicity of most protein
      antigens. We tested seventeen mono- or polyclonal antibodies against peptide or
      protein antigens, including a majority for which immunoreactivity had previously
      been reported to be sensitive to glutaraldehyde fixation. Forebrain sections of
      rats or mice fixed by perfusion with 3.5% glutaraldehyde were processed for pre
      embedding immunocytochemistry by the avidin-biotin method. The resulting
      immunostaining was in most cases at least similar to that obtained in sections
      fixed with paraformaldehyde. Immunoreactivity against the mouse or human
      neurofilament protein NF-L was even improved, being similar to that previously
      reported for unfixed brain tissue. Of all antigens tested, only choline
      acetyltransferase, phenylethanolamine-N-methyl transferase, and neuropeptide Y
      were detected with lower sensitivity than after paraformaldehyde fixation, which
      was attributed to a rather restricted penetration of the primary antibody into
      glutaraldehyde-fixed tissue sections. These results indicate that glutaraldehyde
      may be envisaged as a possible fixative for optimal immunocytochemical detection
      of any tissue antigen at the electron microscopic level, including antigens
      which, on the basis of results obtained after fixation with paraformaldehyde
      glutaraldehyde mixtures, were considered highly sensitive to glutaraldehyde
      fixation.

PMID- 8537645
TI  - Effect of antibody alone and combined with acyclovir on neonatal herpes simplex
      virus infection in guinea pigs.
AB  - Neonatal herpes simplex virus (HSV) infection produces severe disease with
      unacceptable morbidity and mortality with current antiviral therapies. The effect
      of therapy with passive anti-HSV antibody and acyclovir was evaluated using a
      guinea pig model of neonatal HSV. Newborn animals were inoculated intranasally
      and treated with acyclovir (60 mg/kg/day) or antibody (or both), beginning on
      days 0, 2, or 3 after HSV-2 inoculation. Acyclovir alone was effective only when
      begun on day 0, and antibody alone was effective when begun on or before day 2.
      Only combination therapy was effective on day 3, reducing mortality from 82%
      (14/17) in controls to 44% (7/16; P < .05). Combined therapy also significantly
      reduced the duration of skin, eye, and mouth disease and respiratory symptoms but
      not recurrent disease. These data suggest that addition of antibody therapy to
      acyclovir may improve the outcome of neonatal HSV disease.

PMID- 8537646
TI  - Role of staphylokinase in the acquisition of plasmin(ogen)-dependent enzymatic
      activity by staphylococci.
AB  - In this study, the role of the staphylococcal plasminogen activator,
      staphylokinase (SAK), was analyzed for its ability to mediate acquisition of cell
      associated plasmin-like activity by staphylococci in the presence of a source of
      human plasminogen. A panel of staphylococcal strains isolated from humans was
      tested for the presence of the SAK gene, secretion of the plasminogen activator,
      and the ability to acquire enzymatic activity when incubated with purified human
      plasminogen or serum. When SAK was compared with the eukaryotic plasminogen
      activators, urokinase and tissue plasminogen activator, only SAK could mediate
      acquisition of cell-associated enzymatic activity by staphylococci without first
      generating significant fluid-phase plasmin. These studies provide evidence for a
      novel mechanism by which SAK-producing S. aureus can acquire an unregulatable
      host plasmin-like activity that might contribute to their invasive potential.

PMID- 8537647
TI  - A modified Farr assay is more specific than ELISA for measuring antibodies to
      Streptococcus pneumoniae capsular polysaccharides.
AB  - In an attempt to develop an assay specific for antibody to capsular
      polysaccharide (PS) of Streptococcus pneumoniae, the ability of ELISA and Farr
      (radioactive antigen-binding) assay for antibodies to 6B and 19A PS to be
      affected by antibodies to C-polysaccharide (C-PS) was compared. Preabsorption
      with C-PS reduced values obtained by ELISA for anti-6B antibody by > 3-fold in 5
      of 10 preimmune and 7 of 26 postimmune sera. In contrast, absorption reduced
      values by > 3-fold in 0 of 36 samples studied with the Farr assay. Similar
      results were observed when the absorption was done with CSR-SCS2 S. pneumoniae.
      Furthermore, when anti-19A antibody levels were examined, preabsorption with R36a
      S. pneumoniae reduced ELISA values by 3-fold in 7 of 22 samples, whereas no
      samples had 3-fold reduction by Farr assay. Thus, the Farr assay for capsular PS
      is less affected than the ELISA by anti-C-PS antibody.

PMID- 8537648
TI  - Immunogenicity and efficacy of Streptococcus pneumoniae polysaccharide-protein
      conjugate vaccines against homologous and heterologous serotypes in the
      chinchilla otitis media model.
AB  - Cross-protection among pneumococcal serotypes within serogroups was measured in
      the chinchilla otitis media (OM) model because several serotypes that cause OM in
      children are closely related biochemically. Chinchillas were given tetravalent
      vaccine composed of pneumococcal capsular polysaccharides (PS; types 6B, 14, 19F,
      23F) conjugated to an outer membrane protein complex, and 89% to 96% developed a
      > or = 2-fold serum IgG rise against vaccine PS. Vaccine efficacy was tested by
      inoculating middle ear hypotympanic bullae with Streptococcus pneumoniae types
      6B, 6A, 19F, or 19A. OM severity in the vaccinated groups challenged with types
      6B, 6A, and 19F but not 19A was significantly better than in the respective
      placebo groups. Culture-positive pneumococcal OM occurred in 38%, 62%, 0, and 78%
      of vaccinated chinchillas challenged with types 6B, 6A, 19F, and 19A,
      respectively, but in 88% of type 6B- and 100% of type 6A-, 19A-, and 19F
      challenged placebo chinchillas.

PMID- 8537649
TI  - Subtyping of common pediatric pneumococcal serotypes from invasive disease and
      pharyngeal carriage in Finland.
AB  - Ninety-nine penicillin-sensitive Streptococcus pneumoniae strains of common
      pediatric serogroups/types (6, 7, 14, 19, and 23) cultured from the blood of
      children with invasive disease (n = 49) or asymptomatic oropharyngeal carriage (n
      = 50) were analyzed by multilocus enzyme electrophoresis and ribotyping; 53
      distinctive multilocus enzyme genotypes (ETs) and 53 ribotypes were identified.
      Multilocus enzyme electrophoresis showed good correlation with ribotying. ETs and
      ribotypes among invasive and carriage isolates were similar. Within different S.
      pneumoniae serogroups/types, both clonal (7 and 14) and heterogenous (6, 19, and
      23) ET and rRNA hybridization patterns were observed. Greatest diversity was
      observed among serotypes 6A, 6B, and 19F. Use of 12 additional restriction
      enzymes besides PvuII and BglII did not increase ribotype discrimination within
      serotype 7 and 14 isolates. Serotype 7 and 14 strains, which appear clonal by
      subtyping, are rare among carriers but common causes of invasive disease.
      Characteristics associated with their clonality may represent an advantage for
      invasiveness.

PMID- 8537650
TI  - Antibody-secreting cells and their relation to humoral antibodies in serum and in
      nasopharyngeal aspirates in children with pneumococcal acute otitis media.
AB  - Mucosal and systemic antibody responses to pneumococcal capsular polysaccharide
      were studied in 17 children with culture-verified pneumococcal acute otitis
      media. Serotype-specific antibody-secreting cells (ASCs) in peripheral blood and
      antibodies in acute and convalescent sera and nasopharyngeal aspirates were
      measured. A polysaccharide-specific ASC response was induced in all subjects. The
      response was age dependent, and the dominant antibody class was IgA. Three
      children > 24 months old had > 100 IgA-class ASCs/10(6) cells and serum and
      nasopharyngeal IgA responses; 2 had only a nasopharyngeal IgA response. None of 8
      children < 24 months old showed a systemic response; however, a nasopharyngeal
      IgA response was detected in 1. Results suggest that whole pneumococci can induce
      a mucosal polysaccharide-specific antibody response independent of the systemic
      response. Results are also in accordance with earlier studies suggesting that the
      mucosal immune system matures earlier in life than does the systemic immune
      response.

PMID- 8537651
TI  - Quantitative determination of antibodies to type III group B streptococcal
      polysaccharide.
AB  - The susceptibility of neonates to invasive infection with type III group B
      streptococci (GBS) in a radioactive antigen-binding assay (RABA) has been
      correlated with low maternal serum levels of capsular polysaccharide-specific
      antibodies. An ELISA was developed using capsular polysaccharide covalently
      coupled to human serum albumin. In sera from 35 healthy women, the range of IgG
      antibodies to GBS III polysaccharide was 0.05-33.0 micrograms/mL, and specific
      IgA antibodies were 0.08-1.1 micrograms/mL; however, no GBS III capsular
      polysaccharide-specific antibodies of the IgM isotype were detected by the ELISA.
      The levels of naturally acquired and vaccine-induced antibodies obtained with
      this ELISA correlated well with the results of the RABA (Spearman's rank
      correlation coefficient, .92). The ELISA has two major advantages over the RABA:
      It measures specific isotypes and subclasses of antibodies, and it can detect
      type III polysaccharide-specific antibodies at lower concentrations.

PMID- 8537652
TI  - Molecular genetics of resistance to both ceftazidime and beta-lactam-beta
      lactamase inhibitor combinations in Klebsiella pneumoniae and in vivo response to
      beta-lactam therapy.
AB  - The molecular basis of ceftazidime resistance in 2 isolates of Klebsiella
      pneumoniae was studied. The first (21300) expressed resistance to ceftazidime and
      piperacillin-tazobactam. The second (26139) expressed resistance to ceftazidime
      but remained susceptible to piperacillin-tazobactam. The 2 strains harbored
      similar large plasmids that hybridized to TEM- and SHV-related beta-lactamase
      genes. An Escherichia coli strain harboring the plasmid conferring resistance to
      both compounds (pLRM7) produced beta-lactamases of pI 5.9 (TEM-6) and pI 7.6 (SHV
      1). E. coli harboring the other plasmid (pLRM8) expressed only the TEM enzyme
      because of insertion of IS15 within blaSHV-1. In vivo studies suggested that
      resistance to beta-lactam-beta-lactamase inhibitor combinations conferred by
      pLRM7 will be clinically important. Clinical resistance to both extended-spectrum
      cephalosporins and beta-lactam-beta-lactamase inhibitor combinations is
      achievable via the production of two enzymes, with only one possessing an
      extended spectrum of activity.

PMID- 8537653
TI  - Neutralization of macrophage inflammatory protein-2 attenuates neutrophil
      recruitment and bacterial clearance in murine Klebsiella pneumonia.
AB  - The role of macrophage inflammatory protein-2 (MIP-2) in bacterial pneumonia was
      characterized. Mice were challenged with Klebsiella pneumoniae intratracheally,
      and organs were harvested at 8, 24, and 48 h. Inoculation with K. pneumoniae
      resulted in the time-dependent expression of MIP-2 mRNA and protein within the
      lung, which was maximal 48 h after inoculation. Mice were then passively
      immunized with rabbit anti-murine MIP-2 serum intraperitoneally 2 h before
      administration of K. pneumoniae. Treatment with anti-MIP-2 serum resulted in a
      60% decrease in lung neutrophil (PMNL) influx and a significant increase in K.
      pneumoniae colony-forming units in both lung and liver homogenates. Finally,
      treatment with anti-MIP-2 serum decreased early (48-72 h) but not late (after 72
      h) survival in animals with Klebsiella pneumonia. This study indicates that MIP-2
      is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in
      vivo results in decreased PMNL influx and lung bacterial clearance in murine
      Klebsiella pneumonia. MIP-2 is produced during Klebsiella pneumonia and
      inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung
      bacterial clearance in murine Klebsiella pneumonia.

PMID- 8537654
TI  - Neuroprotective effect of excitatory amino acid antagonist kynurenic acid in
      experimental bacterial meningitis.
AB  - Sustained high-level exposure to glutamate, an excitatory amino acid
      neurotransmitter, leads to neuronal death. Kynurenic acid attenuates the toxic
      effects of glutamate by inhibition of neuronal excitatory amino acid receptors,
      including the N-methyl-D-aspartate subtype. To evaluate the role of glutamate in
      causing neuronal injury in a rat model of meningitis due to group B streptococci,
      animals were treated with kynurenic acid (300 mg/kg subcutaneously once daily) or
      saline beginning at the time of infection. Histopathologic examination after 24
      72 h showed two distinct forms of neuronal injury, areas of neuronal necrosis in
      the cortex and injury of dentate granule cells in the hippocampus. Animals
      treated with kynurenic acid showed significantly less neuronal injury (P < .03)
      in the cortex and the hippocampus than did untreated controls. These results
      suggest an important contribution of glutamate to neurotoxicity in this animal
      model of neonatal meningitis.

PMID- 8537655
TI  - The influence of capsulation and lipooligosaccharide structure on neutrophil
      adhesion molecule expression and endothelial injury by Neisseria meningitidis.
AB  - Host inflammatory response to meningococcal infection is believed to be a major
      determinant of disease severity. Isogenic mutants of Neisseria meningitidis
      serogroup B1940, which differ in expression of capsular polysaccharide and
      lipooligosaccharide (LOS), were used to examine host responses in a whole blood
      model of bacteremia and a model of endothelial injury. The parent organism caused
      significantly less neutrophil shedding of the adhesion molecule, L-selectin, than
      the three mutant organisms (P < .01) and was most resistant to the bactericidal
      activity of whole blood. Despite marked differences in bacterial adhesion to
      endothelial cells (P < .05), no damage was induced by organisms alone.
      Endothelial injury was observed when neutrophils were incubated with adherent,
      capsule-deficient organisms (P < .05). The degree of endothelial damage was
      related to the number of neutrophils adherent to the endothelium. Thus, bacterial
      capsulation and LOS structure can influence neutrophil activation and endothelial
      injury and, as such, may be important in the pathogenesis of meningococcal
      sepsis.

PMID- 8537656
TI  - Liposome-encapsulated (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for
      long-acting therapy of viral retinitis.
AB  - The effect of liposome-encapsulated (S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine (HPMPC; cidofovir) was evaluated as prophylaxis
      in a rabbit model of experimentally induced retinitis caused by preretinal
      inoculation of herpes simplex virus type 1 (HSV-1). Cidofovir (100 micrograms) in
      liposomes (0.1 mL) was injected intravitreally 10-120 days before retinal
      inoculation with HSV-1. Twenty-two of 26 eyes pretreated with liposome
      encapsulated cidofovir 10-60 days before HSV-1 inoculation were protected from
      experimentally induced retinitis, and 2 of 5 eyes pretreated 120 days before
      inoculation were protected. Intravitreal levels of cidofovir were low (0.7
      microgram/mL) but detectable 120 days after injection. One 100-micrograms
      intravitreal injection of liposome-encapsulated cidofovir appears to have a
      remarkably potent and prolonged (up to 4 months) antiviral effect in this
      experimental model of HSV-1 retinitis. Since HPMPC is even more potent against
      cytomegalovirus than HSV-1, liposome-encapsulated cidofovir may prove to be
      effective local therapy for AIDS patients with cytomegalovirus retinitis.

PMID- 8537657
TI  - A virulent nonencapsulated Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae strain INT1 was isolated from the blood of a
      young child with clinical signs of meningitis following acute otitis media. No
      immunologic or anatomic predisposition of this child for invasive bacterial
      infection with an unusual organism was documented. Sensitive ELISA proved the
      absence of intra- or extracellular capsular polysaccharide production by INT1 and
      Southern blot analysis confirmed the lack of an intact capsulation (cap) gene
      locus within the chromosome. Nevertheless, INT1 established bacteremia and
      meningitis in infant and weanling rat models of invasive H. influenzae infection.
      High-molecular-weight DNA isolated from INT1 was shown to confer an invasive
      phenotype on transformation of a nonencapsulated, avirulent laboratory strain of
      H. influenzae. Together these findings imply the presence of one or more as-yet
      undiscovered, noncapsular virulence factors of H. influenzae that are capable of
      mediating invasive disease and resistance to immunologic clearance.

PMID- 8537658
TI  - Suppression of acute Ixodes scapularis-induced Borrelia burgdorferi infection
      using tumor necrosis factor-alpha, interleukin-2, and interferon-gamma.
AB  - Down-regulation of mammalian cytokine production has been demonstrated during
      tick feeding. To examine the hypothesis that reconstitution of cytokines during
      tick feeding could facilitate immune containment of Borrelia burgdorferi, the
      following experiments were done. C3H/HeJ mice were given cytokines for 10 days
      after Ixodes scapularis attachment. At day 21, ear biopsies were analyzed for B.
      burgdorferi. Polymerase chain reaction analysis indicated a protection rate of
      95% in mice receiving tumor necrosis factor (TNF)-alpha. Mice that received
      interleukin (IL)-2 or interferon (IFN)-gamma had infection rates of 30%-45%
      compared with 83% for untreated controls. No correlation was noted between
      neutralizing antibody, reactivity by Western blot, and subsequent protection.
      Culture of B. burgdorferi in cytokine-conditioned media indicated that TNF-alpha,
      IFN-gamma, and IL-2 were not cytotoxic for B. burgdorferi. These data suggest
      that cytokine-induced protection from B. burgdorferi infection was immune
      mediated and that cellular immunity may be associated with protection from I.
      scapularis-induced infection.

PMID- 8537659
TI  - Characterization of the catalase-peroxidase gene (katG) and inhA locus in
      isoniazid-resistant and -susceptible strains of Mycobacterium tuberculosis by
      automated DNA sequencing: restricted array of mutations associated with drug
      resistance.
AB  - The catalase-peroxidase gene (katG) and a two-gene locus (inhA) containing
      mutations associated with resistance to isoniazid in Mycobacterium tuberculosis
      were sequenced in 34 resistant and 12 susceptible strains. Virtually all
      resistant organisms had amino acid changes in KatG or nucleotide substitutions
      upstream of inhA. A region of katG encoding two amino acids frequently altered in
      resistant strains (residues Ser315 and Arg463) and the inhA locus were sequenced
      in 10 susceptible and 51 isoniazid-resistant isolates from the Netherlands. Most
      (84%) of the resistant isolates had mutations in katG or the inhA locus or lacked
      katG. Together, approximately 75% of isoniazid-resistant isolates had
      replacements at amino acids 315 or 463 in KatG or nucleotide substitutions
      upstream of inhA. All 16 strains of Mycobacterium bovis and Mycobacterium microti
      studied had Leu463 rather than Arg463 in KatG, an observation consistent with the
      hypothesis that Leu463 is the ancestral condition in M. tuberculosis.

PMID- 8537660
TI  - Treatment of experimental gram-negative and gram-positive bacterial sepsis with
      the hematoregulatory peptide SK&F 107647.
AB  - SK&F 107647, a novel synthetic low-molecular-weight peptide, has demonstrated
      potent antiinfective activities in murine models of fungal and viral infection.
      To determine if the hematoregulatory activities of SK&F 107647 could offer
      protection over conventional antibiotic therapy or as a single agent in animal
      models of bacterial sepsis, rats were implanted intraperitoneally with a live
      bacteria-containing fibrin-thrombin clot. Rats pretreated subcutaneously or
      orally with SK&F 107647 and then infected with either a gram-negative
      (Escherichia coli) or a gram-positive (Staphylococcus aureus) bacteria-containing
      clot demonstrated significantly improved survival over control formulation
      treated animals. Treated animals showed increased effector cell activation,
      measured by CD11b expression on neutrophils and monocytes, and up to 1000-fold
      reduction in the number of E. coli recovered from blood. Thus, the
      hematoregulatory activities of SK&F 107647 can increase natural host resistance
      to infections caused by both gram-negative and gram-positive bacteria.

PMID- 8537661
TI  - Intracellular pathways involved in tumor necrosis factor-alpha release by human
      monocytes on stimulation with lipopolysaccharide or staphylococcal peptidoglycan
      are partly similar.
AB  - This study compared the effects of intracellular pathway inhibitors on tumor
      necrosis factor-alpha (TNF-alpha) release from human monocytes. Cells were
      stimulated with peptidoglycan (PG) from Staphylococcus epidermidis or with
      Escherichia coli lipopolysaccharide (LPS), both in the presence of 10% human
      serum. Of 10 substances tested, only the protein tyrosine kinase inhibitor
      tyrphostin AG 126 discriminated significantly between PG and LPS: TNF-alpha
      release induced by PG, but not by LPS, was dose-dependently suppressed. The
      results obtained with other modulatory substances, including different protein
      kinase and G protein inhibitors, suggest that calmodulin-dependent protein
      kinase, protein tyrosine kinase, and a cholera-toxin-sensitive G protein are
      involved in both PG- and LPS-induced TNF-alpha release. Further, drugs such as
      pentoxifylline, chloroquine, and the antioxidant apocynin similarly inhibited TNF
      alpha release by PG- as well as LPS-stimulated cells.

PMID- 8537662
TI  - Risk factors for fluconazole-resistant candidiasis in human immunodeficiency
      virus-infected patients.
AB  - In a case-control study to identify risk factors for fluconazole-resistant
      oroesophageal candidiasis in human immunodeficiency virus-infected patients, 25
      patients with clinical and in vitro fluconazole-resistant candidiasis were paired
      with controls who had treatment-responsive candidiasis and who had been observed
      for similar time periods. After their first episode of candidiasis, patients who
      later developed fluconazole resistance had more treated episodes than did matched
      controls (cases, 3.1; controls, 1.8; P = .004), lower median CD4 cell counts
      (11/mm3 vs. 71/mm/3; P = .004), and greater median durations of all antifungal
      therapy (419 vs. 118 days; P < .001) and of systemic azole therapy (272 vs. 14
      days; P < .001). When paired with a second set of controls matched by CD4 cell
      count as well as first diagnosis of candidiasis, cases continued to show greater
      median exposure to azoles (272 vs. 88 days; P = .005). These data indicate that
      advanced immunosuppression and exposure to oral azoles are risk factors for the
      development of fluconazole resistance.

PMID- 8537664
TI  - Cryptosporidium parvum: intensity of infection and oocyst excretion patterns in
      healthy volunteers.
AB  - Data about human Cryptosporidium parvum infection have originated from travelers,
      community and day care center outbreaks, and persons infected with the human
      immunodeficiency virus. In addition, experimental infection in 29 antibody
      negative, healthy, adult volunteers generated information on the dose-infection
      response of C. parvum (Iowa strain). In that report, low inocula were sufficient
      to cause infection in 18 and illness in 7 persons. To further define the duration
      and intensity of infection in this population, oocyst shedding patterns were
      investigated in the 18 subjects infected with C. parvum. Oocyst quantitation
      revealed that volunteers with diarrheal illness (n = 7) excreted more oocysts
      over the course of the infection than did volunteers without diarrhea (n = 11; P
      < .05). Symptomatic subjects were more likely to shed oocysts on consecutive
      days. Further, a statistical nonsignificant inverse trend (r2 = .330, P = .136)
      was seen between challenge dose and total excreted oocysts. This paradox may
      relate to receptor saturation or a toxic effect on cells, parasites, or both
      afforded by a high inoculum.

PMID- 8537663
TI  - Surface localization, regulation, and biologic properties of the 96-kDa
      alcohol/aldehyde dehydrogenase (EhADH2) of pathogenic Entamoeba histolytica.
AB  - The 96-kDa surface antigen of Entamoeba histolytica was demonstrated through
      extensive immunologic evaluation with monoclonal and monospecific antibodies to
      be identical to or an isoform of the amebic alcohol/aldehyde dehydrogenase
      (EhADH2). EhADH2 was secreted, excreted, or shed into the culture medium in
      quantities commensurate with amebic growth when studied in a novel culture
      system. Of importance, using RNase protection assays, specific mRNA coding for
      the EhADH2 gene product(s) was up-regulated by treatment of viable trophozoites
      with the enzyme substrate ethanol. These data provide insight into the biology of
      this enzyme and its regulation by appropriate stressors.

PMID- 8537665
TI  - Hantavirus serologies in patients hospitalized with community-acquired pneumonia.
AB  - In many patients, the etiology of community-acquired pneumonia is not known but
      may be caused by previously undescribed pathogens in some cases. The recently
      identified hantavirus Sin Nombre (SN) causes hantavirus pulmonary syndrome.
      Because sporadic cases have occurred outside the range of its reservoir (the deer
      mouse Peromyscus maniculatus), an investigation sought to determine whether
      hantaviruses contributed to cases of community-acquired pneumonia in a large
      Baltimore hospital. Acute-phase sera from 385 hospitalized patients with
      pneumonia were examined using an IgG ELISA technique with antigens prepared from
      several hantaviruses: prototype Hantaan (HTN), Seoul (SEO), Puumala (PUU),
      Convict Creek (HN107), and SN. Of 385 sera, 8 (2.1%) showed some reactivity with
      one or more HTN, SEO, or PUU antigens but none had detectable specific IgM
      antibodies. No sera were reactive with SN or HN107 antigens. Thus, hantaviruses
      are an uncommon cause of community-acquired pneumonia in the Baltimore area.

PMID- 8537667
TI  - Tissue macrophages are infected by human cytomegalovirus in vivo.
AB  - On the basis of in vitro experiments, it has been suggested that cells of
      hematopoietic origin play a major role in the pathogenesis and latency of human
      cytomegalovirus (HCMV). To elucidate the in vivo importance of hematopoietic
      cells in acute HCMV infection, tissue sections from various infected organs were
      investigated by immunohistochemical double-labeling analyses. Monoclonal
      antibodies directed against distinct viral and cellular antigens were used to
      identify infected macrophages, polymorphonuclear cells, and lymphocytes.
      Macrophages and polymorphonuclear cells were targets for HCMV infection in
      different tissues. Viral proteins representing all stages of permissive HCMV
      infection were detected in macrophages, suggesting that these cells support the
      complete viral replication cycle. In polymorphonuclear cells, viral gene
      expression was restricted to the immediate early phase, indicating that these
      cells are abortively infected. These findings suggest that macrophages play an
      important role in the hematogenous spread of HCMV into solid organs.

PMID- 8537666
TI  - Use of intrinsic and extrinsic helper epitopes for in vivo induction of anti
      hepatitis C virus cytotoxic T lymphocytes (CTL) with CTL epitope peptide
      vaccines.
AB  - The induction of virus-specific cytotoxic T lymphocytes (CTL) is an important
      part of vaccine strategy. CTL induction in vivo by two hepatitis C virus (HCV)
      peptides containing CTL epitopes, one from the NS5 region (P17) and one from the
      core (C7), was compared. P17 required covalent attachment of a helper peptide
      (PCLUS3 containing a cluster of epitopes from the human immunodeficiency virus
      envelope protein), whereas C7 did not. However, the minimal decapeptide of C7,
      C7A10, alone did not induce CTL. The helper cells induced by PCLUS3-17 or by C7
      were shown to be CD4+ and to produce interleukin-2 (IL-2). Thus, help can be
      supplied by a natural helper epitope intrinsic to the CTL peptide, as in C7, or
      by attaching a helper epitope from another protein, as in the case of P17. The
      cluster peptides may be useful promiscuous helper peptides for a variety of CTL
      epitopes from diverse pathogens.

PMID- 8537669
TI  - Frequent presence of a novel herpesvirus genome in lesions of human
      immunodeficiency virus-negative Kaposi's sarcoma.
AB  - While Kaposi's sarcoma (KS) is extremely common in homosexual men infected with
      human immunodeficiency virus (HIV), it is also found in several clinical settings
      in which HIV infection is absent. Recently, sequences from the genome of a novel
      member of the herpesvirus family have been identified within KS biopsies in the
      AIDS-associated form of the disease. The presence of these sequences was sought
      in 6 cases of HIV-negative KS, including 4 cases of endemic KS from Africa, and
      was found in 5 of the 6. These findings strengthen the association between
      infection with this virus and the development of KS and argue against the notion
      that this association is simply the result of opportunistic superinfection of
      profoundly immunodeficient hosts.

PMID- 8537668
TI  - A community-based study of human immunodeficiency virus type 2 provirus load in
      rural village in West Africa.
AB  - A community-based study of provirus load in human immunodeficiency virus (HIV)
      type 2-infected subjects was done in a rural village in Guinea-Bissau. HIV-2
      provirus load varied considerably, with a geometric mean of 124.3 (95% confidence
      interval, 86.0-179.6) copies/10(5) CD4 cells, which is a level similar to that
      found in HIV-1 infection. Neither malaria parasitemia, active syphilis, or human
      T cell leukemia virus coinfection significantly influenced provirus load, nor did
      age. Eleven of 104 HIV-2-infected subjects had died after 3 years of follow-up; 9
      of those who died had a high provirus load of > or = 100 copies/10(5) CD4 cells
      and a relatively low CD4 cell percentage of < 29%.

PMID- 8537670
TI  - Bactericidal/permeability-increasing protein, a lipopolysaccharide-specific
      protein on the surface of human peripheral blood monocytes.
AB  - Bactericidal/permeability-increasing protein (BPI), a cationic protein present in
      the azurophilic granule and on the surface of polymorphonuclear leukocytes,
      specifically interacts with lipopolysaccharide (LPS). This study demonstrates for
      the first time, using flow cytometry with specific anti-BPI monoclonal antibody
      (MAb), that human peripheral blood monocytes express BPI on their cell surface.
      The monocyte cell surface BPI was shown to bind to LPS, because binding of anti
      BPI MAb 4E3 (which is known not to react with BPI to which LPS is bound) to cell
      surface BPI was strongly reduced after preincubation of cells with LPS. However,
      cell surface BPI did not quantitatively contribute to the interaction of LPS with
      the monocyte cell membrane, since preincubation of cells with 4E3 did not block
      binding of LPS-fluorescein isothiocyanate to monocytes. The origin of the
      monocyte cell surface BPI remains to be further elucidated.

PMID- 8537671
TI  - Pneumococcal conjugate vaccine primes for antibody responses to polysaccharide
      pneumococcal vaccine after treatment of Hodgkin's disease.
AB  - Thirty-nine previously treated Hodgkin's disease (HD) patients were immunized
      with 7-valent pneumococcal conjugate vaccine (7-OMPC) followed by one dose of 23
      valent polysaccharide pneumococcal vaccine (23-PS). To determine the priming
      effect of 7-OMPC vaccine, their antibody responses to six serotypes contained in
      both vaccines were compared to those of 57 HD patients who received 23-PS vaccine
      only. The geometric mean antibody concentrations after immunization with 23-PS
      vaccine were significantly higher for five of the six measured serotypes in HD
      patients primed with 7-OMPC vaccine compared with responses in HD patients who
      received 23-PS vaccine only. The mean of the six antibody concentrations was
      significantly higher for the primed group at 12.5 micrograms/mL and 7.76
      micrograms/mL, respectively (P = .015). Priming with a conjugate vaccine should
      be considered as a strategy to protect high-risk adults.

PMID- 8537672
TI  - Disseminated Mycobacterium avium complex infection in AIDS: immunopathogenic
      significance of an activated tumor necrosis factor system and depressed serum
      levels of 1,25 dihydroxyvitamin D.
AB  - Disseminated Mycobacterium avium complex (MAC) infection is associated with
      considerable morbidity and mortality in patients with AIDS. Because both tumor
      necrosis factor-alpha (TNF-alpha) and 1,25-dihydroxyvitamin D3 (1,25D) may be
      involved in the normal control of MAC infection, these parameters were studied in
      AIDS patients with disseminated MAC infection. Of 53 AIDS patients studied, 24
      had no clinical events, 11 had disseminated MAC infection, and 18 had other
      clinical events. Patients with disseminated MAC infection had significantly
      higher serum levels of both TNF-alpha and soluble TNF receptors compared with
      other AIDS patients; almost half of the MAC-infected patients had TNF bioactivity
      in serum. MAC-infected patients also had severely decreased serum 1,25D levels
      compared with all other AIDS patients. The activation of the TNF system was
      significantly correlated with the degree of 1,25D deficiency. These findings may
      reflect interaction between vitamin D and the TNF system in the pathophysiology
      of disseminated MAC infection in AIDS.

PMID- 8537673
TI  - Mycobacterium avium complex sputum isolates from patients with respiratory
      symptoms in Guinea-Bissau.
AB  - In total, 814 patients with clinically suspected tuberculosis were examined at
      the Raoul Follerau Hospital in Bissau, Guinea-Bissau. Sputum samples were
      collected, and cultures were grown on Lowenstein-Jensen medium. Isolates were
      further characterized by standard biochemical methods and nucleic acid probes for
      Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). Serum samples
      were collected and analyzed for antibodies against human immunodeficiency virus
      (HIV) types 1 and 2. Of 17 patients who had MAC organisms in sputum, 2 were HIV-2
      positive and none was HIV-1-positive. Of the total 814 patients, 189 had culture
      verified tuberculosis; 36 (19%) of them were HIV-2-positive. Thus, of 206
      patients with sputum culture positive for M. tuberculosis or MAC, 17 (8%) had MAC
      organisms in sputum. MAC infection may be the cause of some treatment failures in
      areas where MAC pulmonary infection is common.

PMID- 8537674
TI  - Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in
      AIDS patients.
AB  - The frequency of HLA-DQ antigens in AIDS patients with toxoplasmic encephalitis
      (TE) were examined. HLA-DQ3 was significantly more frequent in white North
      American AIDS patients with TE (85.0%) than in the general white population
      (51.8%; P = .007, corrected P = .028) or randomly selected control AIDS patients
      who had not developed TE (40.0%; P = .016). In contrast, the frequency of HLA-DQ1
      was lower in TE patients than in healthy controls (40.0% vs. 66.5%, P = .027),
      but this difference did not reach statistical significance when corrected for the
      number of variables tested (corrected P = .108 for the general white population).
      HLA-DQ3 thus appears to be a genetic marker of susceptibility to development of
      TE in AIDS patients, and DQ1 may be a resistance marker. These HLA associations
      with disease indicate that development of TE in AIDS patients is affected by a
      gene or genes in the HLA complex and that HLA-DQ typing may help in decisions
      regarding TE prophylaxis.

PMID- 8537675
TI  - Impairment of tetanus toxoid-specific Th1-like immune responses in humans
      infected with Schistosoma mansoni.
AB  - After vaccination with tetanus toxoid (TT), TT-specific immune responses in
      humans infected with Schistosoma mansoni were assessed. Peripheral blood
      mononuclear cells (PBMC) from vaccinated infected subjects and vaccinated
      uninfected controls were evaluated for their ability to produce cytokines
      characteristic of Th1 or Th2 cells (interferon [IFN]-gamma or interleukin [IL]-4,
      respectively) after in vitro restimulation with TT. TT-specific IFN-gamma
      production by PBMC from infected subjects was inversely related to infection
      intensity and was significantly lower than TT-specific IFN-gamma production by
      control PBMC. PBMC from all of the infected subjects and 3 of the 5 controls
      analyzed by reverse transcriptase-polymerase chain reaction transcribed the IL-4
      gene in response to TT restimulation. Together, these results suggest that S.
      mansoni-infected persons mount a Th2-like response to the bystander antigen TT,
      while uninfected persons mount a Th1- or Th0-like response.

PMID- 8537676
TI  - Population pharmacokinetics of didanosine in patients with human immunodeficiency
      virus infection.

PMID- 8537677
TI  - V beta expression in healthy subjects and during streptococcal infection.

PMID- 8537678
TI  - Distinction between parasitologic and clinical efficacy of antimalarial agents.

PMID- 8537679
TI  - Molecular epidemiology of measles virus: identification of pathways of
      transmission and implications for measles elimination.
AB  - The nucleotide sequences of either the hemagglutinin or nucleoprotein genes from
      wild type measles viruses isolated in the United States between 1989 and 1992
      differed by < 0.5%. This suggests that the majority of viruses associated with
      resurgence of measles in the United States belonged to a single indigenous
      genotype. In contrast, wild type viruses isolated from sporadic outbreaks of
      measles in the United States during 1994 were genetically heterogeneous. These
      viruses were more closely related to wild type viruses previously circulating in
      Europe, Africa, or Japan and were epidemiologically linked to importations or no
      known source. In addition to demonstrating the utility of genetic analysis in
      understanding the epidemiology of measles, these data suggest that the
      transmission of the indigenous virus was interrupted after the 1989-1992
      epidemic. Measures to further reduce the incidence of measles in the United
      States should include efforts to control importation and subsequent spread of
      measles.

PMID- 8537680
TI  - Elevated plasma levels of tumor necrosis factor (TNF)-alpha, soluble TNF
      receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with
      renal syndrome.
AB  - Plasma levels of cytokines were measured by EIA in 15 subjects hospitalized with
      nephropathia epidemica, a European form of hantavirus-induced hemorrhagic fever
      with renal syndrome. Concentrations of tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 were increased in all patients at admission, and the
      concentration of IL-10 was increased in most. TNF-alpha concentrations were still
      increased 1 week after onset of disease; levels of IL-6 and IL-10 were
      normalized. TNF-alpha was undetectable by the WEHI cell assay in serum samples
      obtained throughout the acute phase of disease. Serum levels of the two soluble
      TNF receptors p55 and p75 correlated with levels of the cytokine, indicating that
      receptor binding may be the reason for lack of bioactivity in vitro. TNF-alpha is
      known to induce pathophysiologic and clinical changes similar to those seen in
      nephropathia epidemica and in diseases caused by other hantaviruses.

PMID- 8537681
TI  - Effective immunization with live attenuated influenza A virus can be achieved in
      early infancy. Pediatric Care Center.
AB  - The immunogenicity of vaccines can be modified in infancy by maternal antibodies
      and other immunizations. Hence, the safety and immunogenicity of two doses of
      10(7) TCID50 of live, attenuated cold-adapted (ca) influenza A/Kawasaki/86 (H1N1)
      reassortant virus vaccine given with or apart from childhood immunizations were
      evaluated in infants, starting at 2, 4, or > 6 months of age, in randomized,
      double-blind trials. The ca vaccine was safe and did not significantly reduce the
      immunogenicity of the childhood vaccines in these infants. Infectivity of ca
      virus (virus shedding, > or = 4-fold rise in serum hemagglutination inhibition
      antibody titer, or both) was affected by age, quantity of ca virus given, and
      prior ca virus infection. Two doses of 10(7) TCID50 of ca influenza virus
      infected all infants, indicating that both doses are probably needed to achieve
      immunity against influenza in infants < 6 months of age.

PMID- 8537682
TI  - Protection of MN-rgp120-immunized chimpanzees from heterologous infection with a
      primary isolate of human immunodeficiency virus type 1.
AB  - Three chimpanzees immunized with recombinant gp120 from human immunodeficiency
      virus type 1 (HIV-1) strain MN and 1 control animal were challenged intravenously
      with a primary isolate of HIV-1SF2. Viral infection was detected in the control
      animal by viral culture, polymerase chain reaction, and multiple serologic assays
      beginning 2 weeks after infection. Markers of HIV-1 infection were not detected
      in any of the gp120-vaccinated animals during 12 months of follow-up. Antisera
      from the gp120-immunized chimpanzees were unable to neutralize the challenge
      virus cultured in peripheral blood mononuclear cells (PBMC). These studies
      demonstrate that immunization with recombinant gp120 derived from a T cell
      adapted isolate prevented infection by a heterologous primary isolate of HIV-1.
      The results suggest that in vitro virus neutralization assays utilizing primary
      isolates cultured in PBMC may be imperfect indicators of protection in vivo.

PMID- 8537683
TI  - Neutralizing and infection-enhancing antibody responses to human immunodeficiency
      virus type 1 in long-term nonprogressors.
AB  - Serum antibodies from human immunodeficiency virus type 1 (HIV-1)-infected long
      term non-progressors (LTNPs) and non-LTNPs were evaluated for virus
      neutralization and infection enhancement in vitro. Sera from LTNPs had higher
      average titers of neutralizing antibodies to HIV-1 strains IIIB and MN and more
      frequently neutralized primary isolates from progressors (14.9% vs. 1.3%, P =
      .002). Replication-competent HIV-1 was isolated from peripheral blood mononuclear
      cells and lymph nodes of 3 LTNPs. All viruses from LTNPs had a non-syncytium
      inducing phenotype, were resistant to neutralization by autologous serum obtained
      at the time of virus isolation, and showed little evidence of a heightened
      sensitivity to neutralization by heterologous sera. Complement-mediated, antibody
      dependent enhancement (C'-ADE) of HIV-1IIIB and primary isolates was equally
      prevalent for sera from LTNPs and non-LTNPs. Results indicate that LTNPs produce
      vigorous serum antibody responses and that long-term nonprogression is not
      associated with homologous neutralization or the absence of C'-ADE.

PMID- 8537684
TI  - Laboratory diagnosis of infection status in infants perinatally exposed to human
      immunodeficiency virus type 1.
AB  - Accurate and timely diagnosis of infection status in infants born to women
      infected with human immunodeficiency virus (HIV) is of paramount importance. The
      comparative accuracy of five diagnostic decision rules was evaluated in 208 HIV
      exposed infants (32 infected, 176 uninfected) based on laboratory testing during
      the first 6 months of life. Diagnostic rules A and B, which required single blood
      samples analyzed by culture and polymerase chain reaction (PCR) (rule A) or
      culture, PCR, and p24 antigen detection (rule B) were more prone to incorrect
      diagnoses than were rules requiring 2 blood samples analyzed by a single assay
      (rule C) or combinations of culture and PCR (rules D and E). Rule D, which used
      PCR as the initial test, established the most useful algorithm: a positive PCR
      result followed by a positive culture in the second sample confirmed infected
      status, while two consecutive negative PCR results reconfirmed as negative at 6
      months of age established uninfected status.

PMID- 8537685
TI  - Herpes simplex virus protein targets for CD4 and CD8 lymphocyte cytotoxicity in
      cultured epidermal keratinocytes treated with interferon-gamma.
AB  - In early recurrent herpetic lesions, CD4 T lymphocytes are the predominant
      infiltrating cells, and keratinocytes expressing major histocompatibility complex
      (MHC) class II antigens, induced by interferon-gamma (IFN-gamma), are the major
      site of herpes simplex virus (HSV) replication. IFN-gamma pretreatment of human
      keratinocytes in vitro reduced MHC class I antigen down-regulation by HSV-1
      infection and induced expression of HLA-DR that was unaltered by subsequent HSV-1
      infection. Incubation of these infected keratinocytes with phosphonoacetic acid
      (PAA) almost completely inhibited expression of four major HSV glycoproteins,
      although expression of early proteins was not affected. Weak CD8 T lymphocyte
      cytotoxicity against IFN-gamma-stimulated, HLA-DR-expressing HSV-1-infected
      keratinocytes was consistently directed to the immediate early/early proteins
      (all 9 patients tested) but against late proteins to a lesser degree (4/9
      patients). However, CD4 T lymphocyte cytotoxicity was much greater and directed
      predominantly against late HSV-1 glycoproteins (all 9 subjects tested) in these
      cells.

PMID- 8537686
TI  - Factors associated with cytomegalovirus infection among human immunodeficiency
      virus type 1-seronegative and -seropositive women from an urban minority
      community.
AB  - Cytomegalovirus (CMV) seroprevalence and genital tract shedding in human
      immunodeficiency virus (HIV)-seronegative and HIV-seropositive women from an
      urban minority community were investigated. CMV seropositivity was high in both
      groups: 181 (95.2%) of 190 HIV-negative and 158 (90.3%) of 175 HIV-positive
      subjects. Cervicovaginal shedding was detected in 8 (4.4%) CMV-positive HIV
      negative subjects and 31 (19.6%) HIV-positive subjects (odds ratio [OR], 5.28; P
      < .001). Multiple logistic regression analysis revealed that CMV shedding was
      independently associated with younger age (OR = 0.90; P < .001) and concurrent
      Chlamydia trachomatis or Neisseria gonorrhoeae infection (OR = 3.60; P = .08).
      However, shedding was observed over a broad age range in HIV-positive subjects,
      with 54.8% of shedders being > or = 30 years old. Among HIV-positive subjects,
      CMV shedding was also associated with decreased CD4 cell counts (P = .04) and,
      compared with HIV-negative subjects, was significantly higher (P < .001) among
      subjects with CD4 cell counts < 500 x 10(6)/L (26.5% in subjects with counts < or
      = 200 and 22.1% in subjects with counts of 201-499 x 10(6)/L).

PMID- 8537687
TI  - Effect of human immunodeficiency virus type 1 infection on the antibody response
      to a glycoprotein conjugate pneumococcal vaccine: results from a randomized
      trial.
AB  - Adults (n = 282) were randomized to receive either a pneumococcal glycoprotein
      conjugate vaccine, composed of pneumococcal serotypes 6B, 14, 18C, 19F, and 23F
      linked to CRM197, or a 23-valent pneumococcal polysaccharide vaccine. Among human
      immunodeficiency virus (HIV)-uninfected persons, conjugate vaccine elicited
      significantly higher IgG antibody geometric mean titers (GMTs) than did
      polysaccharide vaccine for serotypes 6B, 18C, and 23F: IgG GMTs were 9.0 versus
      4.8, 23.2 versus 5.9, and 15.3 versus 4.4 micrograms/mL, respectively. In
      contrast, the two vaccines elicited similar antibody GMTs in HIV-infected
      persons: GMTs ranged from 1.3 to 10.8 micrograms/mL for all serotypes. Of note,
      among persons receiving polysaccharide vaccine, antibody GMTs in HIV-uninfected
      and -infected persons with CD4 lymphocytes > or = 500/microL were similar. These
      data underscore the importance of controlled clinical evaluations of newer
      pneumococcal vaccines in all high-risk groups for whom pneumococcal immunization
      is recommended and highlight the need for early immunization of HIV-infected
      persons with currently available polysaccharide vaccines.

PMID- 8537689
TI  - Effect of tampon composition on production of toxic shock syndrome toxin-1 by
      Staphylococcus aureus in vitro.
AB  - To determine whether tampons composed of cotton or rayon differ in their effects
      on production of TSST-1 in vitro, two methods of bacterial cultivation, with and
      without agitation, were used to study the effects of 16 commercially available
      and experimental tampons on production of TSST-1. Experiments were done in
      blinded fashion. TSST-1 was produced in medium alone in the absence of a tampon
      by both methods. Neither cotton nor rayon tampons consistently increased toxin
      production, nor were there significant differences between them in their effects
      on TSST-1. In contrast, a tampon composed of carboxymethylcellulose and polyester
      foam increased production of TSST-1 to a large degree in both culture systems.
      Thus, neither cotton nor rayon amplifies production of TSST-1 in vitro, and
      cotton tampons cannot be claimed to be inherently safer on the basis of such
      data.

PMID- 8537688
TI  - Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in patients
      with human immunodeficiency virus infection: a double-blind, randomized trial.
      ANRS 005-ACTG 154 Group Members. Agence Nationale de Recherche sur le SIDA. AIDS
      Clinical Trial Group.
AB  - Pyrimethamine (50 mg) with folinic acid (15 mg) given three times weekly was
      assessed as primary prophylaxis for toxoplasmic encephalitis (TE) in 554 human
      immunodeficiency virus-infected patients seropositive for Toxoplasma gondii and
      with < 200 CD4 cells/mm3. At 1 year, the incidence of TE was similar in
      pyrimethamine, 12%, and placebo, 13%, groups (relative risk [RR], 0.9; 95%
      confidence interval [CI], 0.6-1.4), and the survival rate was also similar, 85%
      and 80%, respectively (RR, 0.9; 95% CI, 0.7-1.2). Rash was the only adverse event
      that appeared significantly more frequently in the pyrimethamine arm (7% vs. 1%).
      In the on-treatment analysis, the incidence of TE was lower in the pyrimethamine
      arm, 4%, than in the placebo arm, 12% (P < .006). Thus, pyrimethamine cannot be
      recommended as a first-line regimen for primary prophylaxis of TE if the patient
      can take cotrimoxazole. However, it should be considered for patients who are
      intolerant to cotrimoxazole, especially in high-risk patients with < 100 CD4
      cells/mm3.

PMID- 8537690
TI  - Analgesic effect of topical opioids on painful skin ulcers.

PMID- 8537691
TI  - Physician knowledge and attitudes about cancer pain management: a survey from the
      Minnesota cancer pain project.
AB  - The purposes of the study were to determine the knowledge and attitudes about
      cancer pain management (CPM) among practicing physicians in six Minnesota
      communities and to determine the physician-related barriers to optimal CPM.
      Eligible community physicians were surveyed by telephone. The study analyzed
      responses of 145 physicians (response rate, 87%). The majority of the physicians
      were primary care specialists (73%). Significant knowledge deficits were
      identified in nine of 14 CPM principles, but inappropriate attitudes were found
      in only two of nine CPM concepts. Medical specialty had the strongest influence
      on knowledge and attitudes, with primary care physicians having significantly
      better outcomes than surgeons or medical subspecialists. Effective education
      strategies must address knowledge deficits, attitudes, and motivations of the
      relevant peer group influencing physicians, as well as those of individual
      physicians. The Minnesota Cancer Pain Project is testing strategies to enhance
      CPM by physicians and improve patient outcomes.

PMID- 8537692
TI  - Comparison of two different concentrations of hyaluronidase in patients receiving
      one-hour infusions of hypodermoclysis.
AB  - The purpose of this randomized, double-blind study was to compare 300 units of
      hyaluronidase per one-half liter to 150 units per one-half liter in patients
      receiving brief infusions for subcutaneous hydration. Twenty-five evaluable
      patients were randomized to receive a local injection of 300 units of
      hyaluronidase or 150 units of hyaluronidase immediately before two 1-hr infusions
      of two-thirds dextrose 5% and one-third normal saline solution (500 cc volume).
      The following day a crossover took place, and patients received the alternate
      treatment before each of the two 1-hr infusions. The intensity and swelling as
      reported by the patient (visual analogue scale 0-100), and the intensity of edema
      and rash as assessed by the investigator (score 0-4) were not significantly
      different between groups. The patients' and investigators' final choice was also
      not significantly different. Patients could not distinguish between bolus and
      their previous experience with overnight clysis. Our results suggest that brief
      infusions are well tolerated for subcutaneous hydration of patients with advanced
      cancer. A concentration of 150 units of hyaluronidase per one-half liter is well
      tolerated in this population.

PMID- 8537693
TI  - Mucositis management practices for hospitalized patients: national survey
      results.
AB  - The optimal management strategies for cancer chemotherapy and radiotherapy
      induced mucositis have not been identified. In 1989, the National Institutes of
      Health (NIH) published a consensus statement outlining a standardized approach
      for the prevention and treatment of oral complications. The purpose of this
      survey was to identify the national treatment practices for oral mucositis,
      mucocutaneous Herpes simplex virus infections, and oral candidiasis, and to
      compare them to the NIH guidelines. Surveys were mailed to clinical pharmacists
      at 200 hospitals throughout the United States. Sixty-two of the 200
      questionnaires were completed and returned. Institutions used a diversity of
      agents, generating substantial variability in mucositis prophylaxis and treatment
      protocols. Many of these therapies included products or combinations of
      ingredients that lack proven clinical efficacy. Mucositis management strategies
      for hospitalized patients vary widely at US hospitals. Coordinated, controlled
      studies are needed to identify optimal therapies for these patients.

PMID- 8537694
TI  - Effectiveness of levosulpiride versus metoclopramide for nausea and vomiting in
      advanced cancer patients: a double-blind, randomized, crossover study.
AB  - The antiemetic efficacy of levosulpiride (L) was compared to metoclopramide (M)
      in a double-blind, randomized, crossover study. Thirty patients with advanced
      cancer, who were no longer receiving antineoplastic therapy, were randomly
      assigned to receive either L 75 mg/day or M 30 mg/day. After 7 days, patients
      were crossed over to the alternate treatment, which was also given for 7 days.
      The hours with nausea were 1.08 (mean value/day/patient) during treatment with L
      and 2.01 with M (P = 0.002), independent of the order of administration. The
      nausea intensity was 0.76 (mean value/day/patient) with L and 1.42 with M (P =
      0.0004). Complete control of nausea was obtained in 84.6% of patients receiving L
      and 42.3% of those treated with M (P = 0.0034). The number of vomiting episodes
      was 0.38 (mean value/day/patient) during treatment with L and 0.70 with M (P =
      0.002), independent of the order of administration. Vomiting disappeared in 81.5%
      of patients receiving L and 51.8% of those treated with M (P = 0.041). There was
      a carry-over effect in favor of L. These data indicate that both L and M reduce
      nausea and vomiting, but L is more effective.

PMID- 8537695
TI  - Long-term intraspinal infusions of opioids in the treatment of neuropathic pain.
AB  - Long-term intraspinal infusions of opioid drugs are being increasingly utilized
      in patients with noncancer pain. Despite this, there is a lack of long-term
      information, including success and failure rates for pain relief and technical
      problems. During a 5-year period, 18 noncancer patients underwent implantation of
      programmable infusion pumps for long-term intrathecal opioid infusion. Patients
      had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive
      treatments, and (c) obtained greater than 50% pain relief with intrathecal trial
      infusions of morphine sulfate or sufentanil citrate. A disinterested third-party
      reviewer evaluated patients at the most recent follow-up. Sixty-one percent
      (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3
      years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%.
      Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and
      the remaining six patients required higher opioid doses (> 34 mg/day morphine).
      Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief
      in trial infusions and the use of both morphine and sufentanil. Technical
      problems developed in 6/18 patients but appeared to be preventable with further
      experience. Long-term intrathecal opioid infusions can be effective in treatment
      of neuropathic pain but might require higher infusion doses.

PMID- 8537696
TI  - Reduction of nausea and vomiting from epidural opioids by adding droperidol to
      the infusate in home-bound patients.
AB  - In 184 adult patients with severe nonmalignant low back pain from postlaminectomy
      syndrome, temporary lumbar epidural catheters were infused with either 0.25%
      bupivacaine 92 mL, fentanyl 600 micrograms, and droperidol 5 mg (Group A), or
      0.25% bupivacaine 92 mL, fentanyl 600 micrograms, and NaCl 0.9% 2 mL (Group B).
      Infusion rates ranged from 0.5 to 2 mL per hour, with an option for turning the
      infusion off when the patient had no pain and turning it on when the pain
      returned. Infusions were continued from 2 to 55 days, during which time the
      patient was at home. In Group A, only two patients had nausea without emesis,
      while in Group B, nausea occurred in 18 patients (P < 0.04) and four vomited (P <
      0.05). The number of patients with headache, pruritus, somnolence, and/or
      numbness was minimal and without statistically significant group differences.
      During treatments, pain levels were 2 or less on a 10-cm visual analogue scale.
      Added to the epidural infusate, droperidol appears to significantly reduce nausea
      and vomiting in ambulatory patients receiving fentanyl and bupivacaine in
      extended epidural infusions. The possibility that droperidol potentiates
      analgesic effects could not be evaluated.

PMID- 8537697
TI  - Estimating length of survival in end-stage cancer: a review of the literature.
AB  - Accurately estimating survival times in patients with end-stage cancer is on
      ongoing challenge for palliative care clinicians. Psychosocial as well as
      physiological factors have been thought to influence the length of the terminal
      phase of illness, but conclusive findings remain elusive. This review examines
      the studies that have addressed the issue using observable, measurable criteria
      associated with physiological, clinical status. Improving the ability to estimate
      accurately a patient's length of survival may improve patient/family quality of
      life and assist in the efficient, appropriate use of resources. Additional
      research in this and other palliative care issues will need to be better funded
      and organized if progress is to be made.

PMID- 8537698
TI  - Implementation of a formal treatment agreement for outpatient management of
      chronic nonmalignant pain with opioid analgesics.
AB  - We describe the creation and implementation of a formal treatment agreement
      between patients suffering from chronic nonmalignant pain and the pain management
      team at our institution. Key features of the agreement include acknowledgement
      that previous treatment strategies have been inadequate, use of extensive written
      explanations of the side effects and risks of opioid therapy (including the
      potential for addiction), outlining of the conditions under which therapy will be
      conducted, creation of a broad support structure of fully informed health
      professionals to monitor closely and protect the patient, and emphasis on the
      importance of pain relief coupled to enhanced function via the active
      continuation of other therapy. All patients carry a Medical Alert card
      identifying them as participants in the program. During the past 3 years, a total
      of 67 patients with refractory nonmalignant pain have been successfully treated
      with oral opioids using the agreement as a basis for therapy. The treatment
      agreement provides the necessary structure to formalize this therapeutic approach
      and emphasizes the mutual responsibilities of the patient and the pain management
      team.

PMID- 8537699
TI  - Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain.
AB  - Neuropathic cancer pain may be less responsive to opioids than other pain.
      Several studies suggest that N-methyl-D-aspartate (NMDA)-receptor antagonists
      could play a role in the treatment of neuropathic pain. Ketamine is an NMDA
      receptor antagonist that is used as an anesthetic and has been suggested as a
      useful drug for neuropathic pain. Subanesthetic doses of ketamine can yield
      analgesia without hypnosis. We describe a patient who developed neuropathic
      cancer pain unresponsive to opioid escalation and spinal administration of a
      combination of bupivacaine-morphine and was subsequently treated by subcutaneous
      continuous ketamine infusion. A starting dose of 150 mg/day provided good pain
      relief and a dramatic reduction of the oral morphine dose (from 5 g to 200 mg). A
      slow and progressive increase of ketamine and morphine dosage (400 mg and 200 mg
      by the subcutaneous route, respectively) continued to provide adequate pain
      relief after 13 months of therapy despite signs of progressive disease.

PMID- 8537700
TI  - Occult infection as a cause of hip pain in a patient with metastatic breast
      cancer.
AB  - A 39-year-old woman with breast cancer metastatic to bone presented with acute
      hip pain marginally responsive to escalating doses of opioid analgesics.
      Pathologic pelvic fractures were present and there were minimal clinical
      indicators of infection, but the severity and intractable nature of the pain
      prompted further investigation. Computed tomography revealed a pelvic abscess.
      Antibiotic therapy and drainage of the abscess resulted in markedly improved pain
      control, decreased analgesic requirements, and improved quality of life. We
      suggest that, in patients with malignancy, the diagnosis of occult infection
      should be aggressively pursued as a potentially reversible cause of intractable
      pain.

PMID- 8537701
TI  - Is this opioid analgesic tolerance?
AB  - Tolerance to the analgesic effect of opioids is a poorly understood phenomenon.
      While generally accepted to be an uncommon problem, it clearly can present major
      management difficulties in some patients. This case report illustrates different
      aspects of tolerance, describes a management approach using different opioids,
      and provides a focus for discussion of some current developments in understanding
      and managing this problem.

PMID- 8537702
TI  - Problems and coping strategies of families having patients with and without
      deformities.
AB  - Deformity in leprosy is a major problem causing serious socio-economic and
      psychological consequences to the patients and their families, as well as for the
      programmers. This paper examines the nature and extent of social and economic
      problems of leprosy-affected families having patients with and without
      deformities and their strategy to cope with those problems. The data were
      collected from 500 sampled families in two monotherapy districts in Tamilnadu in
      1989-1990. About 20% of the families reported facing socioeconomic problems. The
      proportion of families having patients with deformities facing problems was ten
      times higher (57.3%) than those having patients with no deformities (5.7%).
      Majority of the problems of the affected families were economic. The major
      strategy adopted to deal with economic problems was to adjust within the earnings
      of other family members to make up the loss or reduction in income from the
      patient. The major social problem faced was denial of participation in the
      community. While families with deformed patients adopted "acceptance of their
      existing situation," families with non-deformed patients adopted "avoidance" as
      their coping strategy. Appropriate rehabilitation programmes to restore economic
      security to the patients and their families is called for. There is also the need
      to educate the community about the disease in order to dispel the myths and fears
      associated with leprosy.

PMID- 8537703
TI  - Measurement of dehabilitation in patients of leprosy--a scale.
AB  - Leprosy interferes with the psychological and social life of the patients leading
      to their 'dehabilitation'. Therefore, it is necessary to assess the extent and
      direction of dehabilitation in order to make the treatment plan comprehensive and
      effective. The objective of this work was to: (a) construct a scale for measuring
      dehabilitation and, (b) to standardize it. The methodology included preparation
      of 52 statements (in English) spread over four subareas of life, namely family
      relations, vocational condition, social interaction and self-esteem. It was
      administered to 122 randomly selected respondents. Scores were awarded by summing
      up the weights of each statement, a high score indicating low dehabilitation.
      Statistical tests were applied for standardizing the scale. To establish
      reliability, split-half reliability test and item discriminant analysis were
      used. Factor analysis was used to test the validity. The results show, that the
      split-half reliability coefficient ranged high (from 0.64 to 0.83) in all four
      subareas. The item discriminant analysis had a level of significance of 0.001 for
      42 statements while the factor analysis explained variance covered over 70
      percent. Hence the scale can be an useful intervention strategy for counselling,
      case work or rehabilitation.

PMID- 8537704
TI  - A clinico-epidemiological study of leprosy in arid north-west Rajasthan, Jodhpur.
AB  - A detailed clinical, bacteriological and histopathological study of 1373 patients
      of leprosy who sought medical advice at the Department of Skin, STD and Leprosy
      of Dr. Sampurnanand Medical College, Jodhpur, during 1975-1993 is reported. The
      disease was observed in 1.54 patients per 1000 cases attending in the skin
      department out-patients. More than 50% of them had polar type of lepromatous
      leprosy. The disease was found 2.42 times more often in males than in females and
      was found mainly in the age group 11-70 years. Family history of leprosy was
      obtained in 130 (9.5%) of the cases. Lepra reactions were seen in 151 (11%)
      cases, of which 30 had type 1 reaction (19.2%) and 121 type 2 reaction (80.1%).
      The majority of leprosy cases (966 or 70.4%) were from Jodhpur district, followed
      by 109 (7.9%) from Nagaur district and then from, Barmer, Jaisalmer and Jalore
      etc. All cases of leprosy responded well to the WHO regimens of multidrug
      therapy. The reactional cases were satisfactorily managed with higher doses of
      clofazimine along with oral prednisolone.

PMID- 8537705
TI  - Clinical and electroneurophysiological assessment of leprosy patients on dapsone
      monotherapy--a two year follow-up study.
AB  - Fifty-three persons with tuberculoid type of leprosy having a thickened nerve on
      one side and a clinically normal nerve on the contralateral side were studied
      before, during and after two years of therapy for electrophysiological
      abnormalities in apparently normal and in obviously thickened nerves. Twenty
      seven patients had received treatment with dapsone 100 mg orally and 26 cases had
      received rifampicin therapy. It was found that there was no extension of
      anesthesia or diminution of motor power over a period of two years. There was no
      significant difference between the initial and final recordings of motor and
      sensory nerve conductions if aggregate figures were taken. However, taking
      individual cases, deterioration in nerve conduction (increased latency and
      decreased velocity) was found in two patients, of whom one had received dapsone
      and the other had received rifampicin.

PMID- 8537706
TI  - Localized borderline lepromatous leprosy.

PMID- 8537707
TI  - A case of histoid leprosy responding to ofloxacin along with standard MDT.

PMID- 8537708
TI  - Multiple subcutaneous lipomatosis in a case of relapsed lepromatous leprosy
      masquerading as histoid leprosy.

PMID- 8537709
TI  - Macular lesions in leprosy.

PMID- 8537710
TI  - Sensory testing and disability prevention.

PMID- 8537711
TI  - Relapse in leprosy.

PMID- 8537712
TI  - [Recent progress in hemodialysis].

PMID- 8537713
TI  - [Recent progress in continuous ambulatory peritoneal dialysis].

PMID- 8537714
TI  - [Index for ideal hemodialysis and the evaluation].

PMID- 8537715
TI  - [Renal replacement therapy of patients with chronic diabetic nephropathy].

PMID- 8537716
TI  - [Renal replacement therapy of patients with acute renal failure].

PMID- 8537718
TI  - [Nutritional management in chronic hemodialysis].

PMID- 8537717
TI  - [Anti-hypertensive therapy in chronic hemodialysis].

PMID- 8537719
TI  - [Present significance of home hemodialysis].

PMID- 8537720
TI  - [Problems in patients on long-term hemodialysis].

PMID- 8537721
TI  - [Countermeasure for patients with anemia due to hemodialysis].

PMID- 8537722
TI  - [Countermeasure for patients with bone disease due to hemodialysis].

PMID- 8537723
TI  - [Countermeasure for patients with amyloidosis due to hemodialysis].

PMID- 8537724
TI  - [Countermeasure for patients with cardiovascular diseases due to hemodialysis].

PMID- 8537726
TI  - [Countermeasure for patients with endocrine disorders due to hemodialysis].

PMID- 8537725
TI  - [Countermeasure for patients with cerebrovascular disorders due to hemodialysis].

PMID- 8537727
TI  - [Countermeasure for patients with infectious disease due to hemodialysis].

PMID- 8537728
TI  - [Hemodialysis therapy (discussion)].

PMID- 8537729
TI  - [A case of tuberculous meningitis associated with facial nerve paralysis and MRI
      findings of brain stem lesion].

PMID- 8537730
TI  - [A case of ventricular tachycardia occurred during interferon therapy in chronic
      hepatitis C].

PMID- 8537731
TI  - [A case of primary antiphospholipid antibody syndrome associated with
      procainamide induced systemic lupus erythematosus].

PMID- 8537732
TI  - [A case of acquired factor VIII inhibitor].

PMID- 8537733
TI  - [A case of thyroid sarcoidosis].

PMID- 8537734
TI  - [Prevention of cerebral infarction].

PMID- 8537735
TI  - [Mitochondrial gene abnormalities and diabetes mellitus].

PMID- 8537736
TI  - [Blood coagulation and fibrinolysis in patients with acute coronary syndrome].

PMID- 8537737
TI  - [Molecular biology and clinical study of hematologic diseases].

PMID- 8537738
TI  - [Primary and secondary prevention of colorectal tumors].

PMID- 8537739
TI  - [Water-electrolyte imbalance and posterior pituitary gland hormone].

PMID- 8537740
TI  - [Clinical study of idiopathic pulmonary fibrosis].

PMID- 8537742
TI  - [Abnormalities of the pupils].

PMID- 8537741
TI  - [Clinical study and physiopathology of coronary vasospasm].

PMID- 8537743
TI  - [Sleep disorders].

PMID- 8537744
TI  - [Orthostatic and postprandial hypotension].

PMID- 8537746
TI  - [Urination disorders].

PMID- 8537745
TI  - [Autonomic nervous system disease--sweat disorders].

PMID- 8537747
TI  - [Irritable bowel disease].

PMID- 8537748
TI  - [Physiopathology of heart failure and new approach to the therapy].

PMID- 8537749
TI  - [Etiological significance of humoral nerve factors in congestive heart failure].

PMID- 8537750
TI  - [Role of cytokines in etiological mechanism of congestive heart failure].

PMID- 8537751
TI  - [Efficacy and problems of cardiotonic agents viewed from physiopathology of
      chronic congestive heart failure].

PMID- 8537752
TI  - [Clinical evaluation of ACE inhibitors for therapy of chronic congestive heart
      failure].

PMID- 8537753
TI  - [Treatment of chronic congestive heart failure to improve their quality of life-
      clinical study of thermal vasodilation therapy].

PMID- 8537754
TI  - [Autologous bone marrow transplantation].

PMID- 8537755
TI  - [Bone marrow transplantation and GVH reaction].

PMID- 8537756
TI  - [Peripheral blood stem cell transplantation].

PMID- 8537757
TI  - [Outcome and problems of bone marrow transplantation through Japan Bone Marrow
      Bank].

PMID- 8537758
TI  - [Tokai Bone Marrow Bank and outcome of bone marrow transplantation between
      unrelated donors].

PMID- 8537759
TI  - [Treatment of arrhythmia].

PMID- 8537760
TI  - [Treatment of hyperlipidemia].

PMID- 8537761
TI  - [Oral anticoagulants treatment of thrombosis].

PMID- 8537762
TI  - [Endoscopic treatment of upper gastrointestinal diseases].

PMID- 8537763
TI  - [Complications of dialysis].

PMID- 8537764
TI  - [Treatment of mixed connective tissue disease].

PMID- 8537765
TI  - [Chronic headache--approach from the view of new international classification].

PMID- 8537766
TI  - [Basic and clinical study of pulmonary emphysema].

PMID- 8537767
TI  - [Progress on antiviral agents].

PMID- 8537768
TI  - [Interferon therapy of viral hepatitis].

PMID- 8537769
TI  - [Image diagnosis of heart diseases using new radioisotope compounds].

PMID- 8537770
TI  - [Antiphospholipid syndrome].

PMID- 8537771
TI  - [Differentiation therapy of leukemia].

PMID- 8537772
TI  - [Insulin resistance and arteriosclerosis].

PMID- 8537773
TI  - [Nephritis and cytokines--special reference to the role of basic fibroblast
      growth factor in etiological mechanism of irreversible sclerosing
      glomerulonephritis].

PMID- 8537774
TI  - [MRI diagnosis of spinal cord diseases].

PMID- 8537775
TI  - [Application of thoracoscopy for diagnosis and therapy of respiratory tract
      diseases].

PMID- 8537776
TI  - [Recent trend of tuberculosis].

PMID- 8537777
TI  - Anna's story: narratives of personal experience about being labeled learning
      disabled.
AB  - The narratives of personal experience of an adolescent named Anna provided
      insights into two issues: first, how well her discourse conformed to linguistic
      expectations for the types of narrative traditionally deemed acceptable in
      school, and second, the themes associated with the presentation of self that Anna
      and her peers addressed when talking about their personal experiences as students
      labeled learning disabled. By narrative, we mean the root metaphor for human
      sense-making that is described in the following epigraph by Bruner. We found that
      Anna's narrative differed from typical school-based expectations in that its
      structure was reminiscent of the oral tradition. From the group of students, we
      heard themes of isolation, undervaluing, and oppression. We recommend a more
      thoughtful and respectful approach to educational decision making that gives
      voice to students.

PMID- 8537778
TI  - Stories from the resource room: piano lessons, imaginary illness, and broken-down
      cars.
AB  - The purpose of this qualitative study was to analyze unstructured, open-ended
      interviews with children in the first through sixth grades who were identified
      with specific learning disabilities. The analysis focused on how the children
      felt about their learning disabilities and how they perceived themselves when
      labeled learning disabled. Themes emerged from the data that suggested children
      fabricated stories about (a) where they went during resource time, (b) not being
      able to read, and (c) being called names and feeling bad about themselves. These
      findings were discussed in relation to previous research and implications for
      future placement decisions.

PMID- 8537779
TI  - Bilingual special education teachers' shifting paradigms: complex responses to
      educational reform.
AB  - This study examined the nature and process of change among five bilingual special
      education teachers as they attempted to modify existing instructional practices.
      Three factors affected the change process: (a) The more special education
      training in the teachers' background, the stronger their reductionist
      orientation; (b) change involves shifts in instructional practices and shifts in
      beliefs, and they do not automatically go hand in hand; and (c) change is most
      facilitated at the beginning stages of collaboration by including practicing
      members of the teachers' occupational community as agents of change.

PMID- 8537780
TI  - Beyond the herring sandwich phenomenon: a holistic constructivist approach to
      teacher education.
AB  - This article explains how key principles of holistic constructivism were used to
      revise a graduate teacher education program and develop a portfolio model of
      evaluation. The program is built around individualized portfolios, applied
      projects, collaborative work, student evaluation, and professional presentation
      of student work. Three students in the program discuss how the principles of the
      revised program and the portfolio process affected their education and their
      teaching. The authors present strategies for helping teacher education students
      create innovative educational programs in their schools.

PMID- 8537781
TI  - Addressing the inevitable conflicts in reforming teacher education: one
      department's story.
AB  - Embracing a transformative philosophy of special education teacher education, the
      Department of Special Education at the University of South Florida has undergone
      significant change over the past several years. Perspectives on the foundational
      knowledge for this change and the values guiding its realization are shared in
      this article. Dilemmas arising from the encounter between traditional practice
      and emerging views are described, along with approaches aimed at understanding
      and addressing these conflicts.

PMID- 8537782
TI  - Looking forward: using a sociocultural perspective to reframe the study of
      learning disabilities. VODD group.
AB  - The purpose of this series has been to invite educators involved with individuals
      with learning disabilities to look through other lenses and listen to other
      voices. In this article, the authors use a sociocultural perspective of teaching
      and learning, based on cultural-historical and activity theory, to synthesize the
      articles of this series and to project where inquiry in the field of learning
      disabilities might be headed. A model is used to organize the discussion and help
      illuminate the sociocultural nature of the pathways of ideas, expectations, and
      activities that either foster or hinder students' school experiences. This final
      article invites readers to refocus and reframe their conversations about learning
      disabilities based on the "new visions" that have been presented in this series.

PMID- 8537783
TI  - Who will be learning disabled after the reauthorization of IDEA? Two very
      distinct perspectives.

PMID- 8537784
TI  - Preliminary investigation of ultrasonic root end preparation.
AB  - Recently, an ultrasonic instrument intended for root end preparation during
      periapical surgery has become commercially available. This study evaluated root
      end preparations in 30 extracted human teeth, comparing those prepared with
      ultrasonic instrumentation to teeth prepared in a traditional manner with a
      microhandpiece and to teeth prepared using a combination of the microhandpiece
      and the ultrasonic instrument. Specimens were evaluated for size of preparation,
      preparation debridement, and time required for preparation. Preparations with the
      ultrasonic device were found to be significantly smaller than the other
      techniques evaluated. Traditional and combined techniques resulted in greater
      debridement under the conditions of the study, and only the combined technique
      demonstrated an increase in time required for preparation. Ultrasonic
      instrumentation may provide significant advantages in the treatment of deeply
      fluted roots when an isthmus is present by reducing the risk of root perforation.

PMID- 8537785
TI  - Cytotoxicity evaluation of six root canal sealers.
AB  - Cell cultures of human gingival fibroblasts obtained from healthy patients were
      used to evaluate the toxicity of six different endodontic cements: AH-26, Pulp
      Canal Sealer, Rocanal-R2, Rocanal-R3, Bioseal, and Endomethasone. The toxicity
      was determined by measuring spectrophotometrically at 405 nm the colorimetric
      reaction of N-acetyl-beta-hexosaminidase, an endogenous enzyme, with the
      chromogenic substrate [p-nitrophenol-N-acetyl-beta-D-glucosamide (NAG)]. Severe
      cytotoxicity was observed in the 1- and 2-wk test solutions of AH-26. Pulp Canal
      Sealer and Endomethasone showed low cytotoxicity in the 1- and 2-wk test
      solutions at 24, 48, and 72 h. Moderate cytotoxicity was observed in the 1- and 2
      wk test solutions of Bioseal, except at 48 and 72 h of 1-wk test solutions.
      Rocanal-R2 showed severe cytotoxicity in the 1-wk test solutions at 48 and 72 h,
      and in the 2-wk test solutions at 24, 48, and 72 h. Moderate cytotoxicity was
      seen in the 1- and 2-wk test solutions of Rocanal-R3 only at 24 h.

PMID- 8537786
TI  - A comparative study of the sealing ability of two root canal obturation
      techniques.
AB  - A comparison was made of the ability of two root canal obturating techniques to
      prevent dye microleakage: gutta-percha lateral condensation and mechanically
      plasticized gutta-percha (JS Quick-fill). Twenty central incisors were prepared
      and obturated by each technique. After rendering the teeth transparent, linear
      dye penetration was found to be 0.48 and 0.52 mm, respectively. The difference
      between the two techniques was not significant. As for the distribution of the
      sealing cement (AH26) in the teeth obturated with JS Quickfill, the cement was
      located in the most peripheral zone of the obturation alongside the dentinal
      walls, whereas the gutta-percha was found in the central part of the canal
      obturating material.

PMID- 8537787
TI  - The endodontic file is a disposable instrument.
AB  - Most cutting and machining tools wear when properly operated on intended
      substrates. Little is known about endodontic files when machining on human
      dentin. It was shown earlier that the efficiency of files was very variable when
      evaluated on Plexiglas substrates. The present study of seven different brands
      and types of files was undertaken to understand their wear better when machining
      human dentin. It was shown that all files evaluated rapidly deteriorated when
      machining dentin. This decline in efficiency was significant but different
      within, as well as, among brands. It was suggested that endodontic files be
      disposable.

PMID- 8537788
TI  - A study of the apical microleakage of a gallium alloy as a retrograde filling
      material.
AB  - The feasibility of utilizing mercury-free Gallium alloy GF for retrograde filling
      was investigated by comparing apical microleakage in 184 extracted human teeth.
      The teeth were divided into four experimental and two control groups. Three
      experimental groups were apical cavity retrofillings with the Gallium alloy GF, a
      mercury-containing amalgam, and a glass ionomer. The fourth experimental group
      was filled with gutta-percha and heat-burnished after apicoectomy. After 24 h, 1
      wk, 4 wk, and 12 wk immersion in dye solution, the roots were vertically
      sectioned, and the deepest point of dye penetration was recorded. The glass
      ionomer showed the least leakage, followed by the amalgam group and the gallium
      group (no significant difference). The gutta-percha heat-burnished group
      displayed the greatest leakage. Gallium alloy GF was shown to have an equivalent
      sealing potential to dental amalgam for a retrograde filling material.

PMID- 8537789
TI  - Evaluation of a solvent-softened gutta-percha obturation technique in curved
      canals.
AB  - The purpose of this study was to compare the efficacy of three obturation
      techniques in curved canals. Twenty-four sets of three (triplets) morphologically
      similar molars having root curvatures of 45 to 90+ degrees were assembled.
      Following canal preparation, one sample from each group was obturated by either a
      halothane-dipped, a chloroform-dipped, or an untreated lateral condensation
      technique. Twenty triplets were cleared, evaluated, and graded for homogeneity of
      fill, canal wall adaptation, and replication of internal anatomy. Four triplets
      had windows prepared to expose the apical 6 mm of filling and were viewed with
      scanning electron microscopy. Kruskal-Wallis test of cleared teeth indicated a
      significant difference in favor of the solvent-softened techniques (p = 0.01).
      There was no difference between chloroform- and halothane-dipped groups (p =
      0.03). Scanning electron microscope evaluations of halothane-dipped samples
      revealed more homogeneous fills with greater canal replication than untreated
      gutta-percha. In addition, halothane-treated samples had appreciably less surface
      porosity than chloroform. Lateral condensation of halothane-treated gutta-percha
      was judged to be a viable obturation technique.

PMID- 8537790
TI  - Comparison of the sealing ability of laser-softened, laterally condensed and low
      temperature thermoplasticized gutta-percha.
AB  - This study compared the effectiveness of four different techniques used for
      obturation of single rooted-teeth: lateral condensation, low-temperature gutta
      percha (Ultrafil), vertical condensation of gutta-percha softened by means of
      three different laser devices (argon, CO2, and Nd:YAG), or composite resin
      photopolymerized by argon laser. Seventy single-rooted teeth were instrumented
      using a step-back technique and obturated using one of the methods listed
      previously. To evaluate apical sealing effectiveness techniques, samples were
      subjected to 1% methylene blue dye at 37 degrees C for 7 days. The most extensive
      dye penetration (4.3 mm) was observed in teeth obturated with composite resin,
      followed by gutta-perch laser with CO2 (2.15 mm), and the Nd:YAG laser (3.54 mm).
      Gutta-percha softened with argon laser created an apical seal almost identical to
      that obtained with the lateral condensation and Ultrafil techniques (1.50, 1.45,
      and 1.48 mm of leakage, respectively). These results indicate that the argon
      laser can be used for gutta-percha softening to produce good apical sealing
      results.

PMID- 8537791
TI  - Dentinal heat transmission induced by a laser-softened gutta-percha obturation
      technique.
AB  - In this study, intracanal laser-softened gutta-percha, Ultrafil, and intracanal
      laser-cured composite resin techniques were compared with respect to the
      temperature elevation induced on the outer root surface. The temperature at the
      root surface of 50 single-rooted teeth was measured using a thermovision camera.
      Argon laser produced a rise in temperature of +12.9 degrees C (gutta-percha) and
      +13.3 degrees C (composite resin), respectively. The CO2 laser produced +10.3
      degrees C and Nd:YAG laser produced the highest temperature elevation of +14.4
      degrees C. Low-temperature gutta-percha obturation technique did not produce a
      measurable temperature change on the external root surfaces.

PMID- 8537792
TI  - Infiltrate of chronic lymphocytic leukemia appearing as a periapical radiolucent
      lesion.
AB  - This report presents a case of a mandibular premolar with a vital pulp and a
      periapical radiolucent lesion in a patient with a history of chronic lymphocytic
      leukemia. Biopsy of the lesion revealed an infiltrate of chronic lymphocytic
      leukemia in the mandible, which is quite rare. This lesion may have portended a
      worsening of the patient's condition and downgrading of her prognosis.

PMID- 8537793
TI  - Irreversible pulpal damage of teeth adjacent to recently placed osseointegrated
      implants.
AB  - Three cases of necrosis of previously vital teeth next to osseointegrated implant
      insertion sites are presented. In two cases, the teeth were in the anterior part
      of the lower jaw and exhibited the same pattern of evolution of pulpal damage
      (i.e. a relatively short time to become nonvital).

PMID- 8537794
TI  - Legislative strategies to address firearm violence and injury.

PMID- 8537795
TI  - Oral anticoagulation.

PMID- 8537796
TI  - Topical treatments for head lice.

PMID- 8537797
TI  - Effectiveness of pharmacist consultations.

PMID- 8537798
TI  - Iron prophylaxis in pregnancy.

PMID- 8537799
TI  - Tachypnea as a predictor of pneumonia in febrile children.

PMID- 8537800
TI  - MDI with spacer vs nebulizer in pediatric asthma.

PMID- 8537801
TI  - Calcium channel blockers and myocardial infarction.

PMID- 8537802
TI  - The Doctor's Dilemma updated.

PMID- 8537803
TI  - Improvements in health-related quality of life with sumatriptan treatment for
      migraine.
AB  - BACKGROUND: The debilitating effects of migraine might be reduced in patients
      using an effective migraine medication. The serotonin (5HT1) receptor agonist
      sumatriptan has been shown in clinical trials to alleviate headache and
      associated symptoms in the majority of patients treated. METHODS: Three hundred
      forty-four (344) patients with migraine were allowed to treat an unlimited number
      of migraine attacks for up to 24 months with subcutaneous sumatriptan (6 mg).
      Open-label oral sumatriptan (100 mg) could be used between 1 hour and 24 hours
      after the initial injection for treatment of recurrent or persistent headache. On
      four occasions during the treatment period, patients completed the Medical
      Outcomes Study Short Form-36 Health Survey, a general health status instrument;
      the Migraine-Specific Quality of Life Questionnaire, a disease-specific
      instrument; and a series of questions designed to measure the impact of migraine
      on productivity and disability. RESULTS: Treatment with sumatriptan was
      associated with significant (P < .05) improvements relative to baseline in three
      of the Short Form-36 Health Survey quality-of-life dimensions (Bodily Pain,
      General Health Perceptions, and Social Functioning) and three of the Migraine
      Specific Quality of Life Questionnaire dimensions (Role Function-Restrictive,
      Role Function-Preventive, and Emotional Function). Significant (P < .05)
      improvements in patient-rated productivity and reductions in patient-rated
      disability also occurred during the trial. CONCLUSIONS: Patients using
      sumatriptan to treat migraines for up to 24 months experienced improvements in
      disability and productivity as well as in health-related quality of life as
      measured either by a general health status instrument or a disease-specific
      instrument.

PMID- 8537805
TI  - A randomized controlled trial of oral albuterol in acute cough.
AB  - BACKGROUND: Beta-agonist agents have been used for bronchospasm and cough in a
      variety of settings. We sought to evaluate the efficacy of oral albuterol for
      acute cough in ambulatory adults. METHODS: We performed a prospective,
      randomized, controlled, double-blind clinical trial comparing albuterol 4 mg by
      mouth three times daily for 7 days with placebo in 104 adults. Subjects had cough
      of less than 4 weeks' duration and no evidence of pneumonia, asthma, or chronic
      obstructive pulmonary disease. All subjects were enrolled at the walk-in clinic
      of a rural academic medical center. RESULTS: There was no significant difference
      between treated and control subjects in any measure of efficacy including cough
      severity score, reduction in sleepless nights, utilization of health care, or
      return to full activity. There were significantly more reports of "shakiness" and
      "nervousness" among albuterol-treated subjects than among controls. CONCLUSIONS:
      Oral albuterol should not be used in unselected patients with acute, nonspecific
      cough.

PMID- 8537804
TI  - Effectiveness of breast self-examination prompts on oral contraceptive packaging.
AB  - BACKGROUND: The purpose of this study was to determine if a breast self
      examination (BSE) "prompt" on oral contraceptive pill (OCP) packages would
      improve the frequency and timing of BSE among women who use OCPs. METHODS: Women
      between 13 and 40 years of age who were initiating, restarting, or continuing use
      of OCPs completed a baseline survey that assessed health behavior and practices.
      All received BSE education, and then were randomized to take either OCPs with a
      BSE prompt or regularly packaged OCPs (without BSE prompt) for three cycles.
      Three months later, subjects completed a follow-up survey that assessed BSE
      frequency and timing. A telephone survey of randomly selected subjects conducted
      6 months after the baseline survey assessed BSE compliance after discontinuation
      of the prompt. RESULTS: Of the 907 subjects at baseline, 49.3% performed BSE
      monthly but only 24.5% performed BSE during the correct time of the menstrual
      cycle. Among subjects who never performed BSE prior to the study, 40.3% of prompt
      subjects and 36.4% of the education-only subjects began BSE by the 3-month
      survey. Among subjects who performed BSE less than once per month at baseline,
      50.9% of prompt subjects and 45.5% of education-only subjects increased the
      frequency of BSEs to a monthly basis by the 3-month survey. More women performed
      BSE during the correct time of the menstrual cycle at the 3 month follow-up
      survey (68.1% prompt, 62.2% education only) and 6-month survey (57.4% prompt,
      48.9% education only) when compared with the baseline survey (24.7% prompt, 24.1%
      education only). Ninety-one percent of women in this study expressed a preference
      for a BSE prompt on OCP packaging. CONCLUSIONS: An increased frequency of BSE was
      observed when women were exposed to an OCP package prompt, particularly for women
      who at baseline were already partially compliant with performing monthly BSE. A
      small but significant improvement was observed for correct BSE timing and this
      effect continued after the prompt was removed, although at a reduced level. The
      innovative BSE prompt was overwhelmingly well received by women in this study.

PMID- 8537806
TI  - Patients with personality disorders: functional status, health care utilization,
      and satisfaction with care.
AB  - BACKGROUND: Personality disorders are believed to occur in approximately 10% of
      the adult population, yet they are rarely diagnosed in primary care settings.
      This study compares the functional status, health care utilization, and
      satisfaction with care for patients who were at high risk for a personality
      disorder with those who were at low risk. METHODS: Patients at high risk for
      personality disorders were identified using a standardized psychometric
      instrument, the Structured Clinical Inventory for DSM-III Axis II (SCID-II).
      After assigning patients to risk categories, responses were compared on the
      Medical Outcomes Study Short Form-36, the Beck Depression Inventory, the CAGE
      alcohol use questionnaire, and an adapted version of the RAND Patient
      Satisfaction Questionnaire. RESULTS: Patients who were at high risk for any
      personality disorder had lower functional status, higher risk for depression or
      alcohol abuse, and lower levels of satisfaction with care. These differences
      could not be explained by demographic or socioeconomic differences between high-
      and low-risk patients. Being at high risk for specific personality disorders,
      such as borderline, schizoid, and dependent disorders, was associated with higher
      degrees of functional impairment and greater risk for depression and alcohol
      abuse. Patients at high risk for other disorders, such as obsessive-compulsive,
      narcissitic, and schizotypal, consistently showed no appreciable degree of
      impairment as compared with patients at low risk for any personality disorder.
      Medical care utilization was no higher when personality disorders were examined
      in aggregate, but a marked increase in utilization was noted among patients at
      high risk for histrionic and dependent disorders. CONCLUSIONS: Among primary care
      patients, having a personality disorder is associated with lower functional
      status, lower satisfaction with health care, and higher risk for depression and
      alcohol abuse.

PMID- 8537807
TI  - Health education and patient satisfaction.
AB  - BACKGROUND: The objective of this research was to determine whether patients who
      reported that their physician or other health care professional had discussed
      health education topics with them were more satisfied with their physician than
      were patients who reported they had not. METHODS: Data were from the 1994 Health
      Plan Value Check conducted by the Pacific Business Group on Health (52% response
      rate). The study sample included 5066 employees ranging in age from 19 to 64
      years and representing four large corporations and 21 health plans. This
      population was randomly sampled by company and health plan. Bivariate and
      multivariate analyses were used to assess the relationship between level of
      patient satisfaction with physician and reported discussion of health education
      topics with a physician or other health professional in the last 3 years.
      RESULTS: Patients who reported that their physician or other health care
      professional discussed at least one health education topic with them in the last
      3 years were more likely to be satisfied with their physician (unadjusted odds
      ratio [OR] = 1.96; 95% confidence interval [CI] 1.79 to 2.25) compared with
      patients who did not. In the multivariate model, the relationship remained
      positive and statistically significant (adjusted OR = 1.49; 95% CI, 1.32 to
      1.68). This relationship was observed for patients enrolled in all types of HMOs
      and managed care plans, as well as those with indemnity or fee-for-service
      insurance. CONCLUSIONS: Patients who reported that their physician or other
      health care professional had discussed one or more health education topics with
      them in the last 3 years were more likely to be very satisfied with their
      physician than were patients who reported they had not.

PMID- 8537808
TI  - Quinolones: a practical review of clinical uses, dosing considerations, and drug
      interactions.
AB  - A review of the literature on quinolones reveals numerous clinically relevant
      points regarding indications, dosing considerations, and drug interactions.
      Quinolones are useful in the treatment of several infectious diseases.
      Unfortunately, indiscriminate use of these valuable antimicrobials has resulted
      in increased patterns of resistance. It is important to consider carefully the
      site of infection and the potential pathogens in each patient before dosing.
      Quinolones have excellent oral absorption, with peak serum concentrations
      approaching those achieved with intravenous administration. When prescribing
      quinolones, the dose should be based on estimated creatinine clearance.
      Quinolones are associated with several clinically significant drug interactions.
      Some of these agents are well-documented inhibitors of hepatic metabolism of
      theophylline, caffeine, and warfarin. It has been well documented that divalent
      and trivalent cations in antacids, sucralfate, and some other products
      significantly reduce the absorption of quinolones. Avoidance or proper management
      of these interactions is required to ensure optimal safety and efficacy.

PMID- 8537809
TI  - Cervical intraepithelial neoplasia in pregnancy.
AB  - There is no evidence that cervical intraepithelial neoplasia (CIN) progresses
      more rapidly because of pregnancy. Management of CIN in pregnancy, therefore, is
      conservative. Screening for invasive cancer is done at the first prenatal visit.
      Colposcopically directed biopsy can then be used to rule out invasive cancer.
      Postpartum cytology and colposcopy are important follow-up procedures for these
      women. Cryosurgery for CIN is usually contraindicated in pregnancy. This report
      includes examples of two pregnant patients with high-grade lesions. A diagnostic
      and treatment algorithm based on the current "expert opinion"is presented.

PMID- 8537810
TI  - Jewish holiday hazards.

PMID- 8537811
TI  - Dermatology screening with telemedicine.

PMID- 8537812
TI  - Proteinuria as a marker for organ damage.

PMID- 8537813
TI  - Ethical use of placebos in clinical trials.

PMID- 8537814
TI  - Permeation properties of a Ca(2+)-blockable monovalent cation channel in the
      ectoderm of the chick embryo: pore size and multioccupancy probed with organic
      cations and Ca2+.
AB  - A Ca(2+)-blockable monovalent cation channel is present in the apical membrane of
      the ectoderm of the gastrulating chick embryo. We used the patch clamp technique
      to study several single-channel permeation properties of this channel. In
      symmetrical conditions without Ca2+, the Na+ current carried by the channel
      rectifies inwardly. The channel has an apparent dissociation constant for
      extracellular Na+ of 115 mM at 0 mV and a low density of negative surface charge
      (-0.03 e/nm2) at its extracellular entrance. The minimal pore diameter is
      approximately 5.8 A, as calculated from the relative permeabilities of 10 small
      organic cations. Extracellular application of six large organic cations decreased
      the inward Na+ current in a voltage-dependent manner, which strongly suggests an
      intrachannel block. The presence of at least two ion binding sites inside the
      pore is inferred from the Na+ dependence of the block by the organic cations.
      This hypothesis is strengthened by the fact that the extracellular Ca2+ block is
      also modified by the Na+ concentration. In particular, the rise of the unblocking
      rate with increased Na+ concentrations clearly suggests the presence of an
      interaction between Ca2+ and Na+ inside the channel. A low probability of double
      occupancy at physiological ionic conditions is implied from the absence of an
      anomalous mole fraction effect with mixtures of extracellular Li+ and K+.
      Finally, the absence of inward current at very strong hyperpolarizations and in
      the presence of 10 mM extracellular Ca2+ demonstrates the absence of significant
      Ca2+ current through this channel. It is argued that this embryonic epithelial
      Ca(2+)-blockable monovalent cation channel is related to both L-type Ca2+ channel
      and cyclic nucleotide-gated channels.

PMID- 8537815
TI  - Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in
      guinea pig ventricular cardiomyocytes.
AB  - The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency
      was investigated in single ventricular cardiomyocytes isolated from guinea pig
      hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37
      degrees C with the whole-cell patch clamp method, under K(+)-free conditions. A
      comparison is made between the response to frequency changes for ICa in the basal
      state and after the application of drugs which elevate the level of adenosine
      3',5'-cyclic monophosphate (cAMP) within the cells. Peak basal ICa was reduced
      with an increase in stimulation rate from 0.5 Hz to 1, 2, 3, 4, or 5 Hz. This
      frequency-induced reduction of ICa was enhanced by reduced temperature, was
      unchanged when Na+ or Ba2+ carried the basal Ca2+ channel current, and was
      greatly enhanced after elevating cAMP levels with forskolin, isoprenaline, or 8
      (4-chlorophenylthio)-cyclic AMP. We examined the mechanism of the enhancement of
      the frequency-induced reduction of ICa by cAMP, and found two conditions which
      abolished it: (a) application of isoprenaline when Na+ carried the Ca2+ channel
      current in Ca(2+)-free solution, or (b) application of 3-isobutyl-1
      methylxanthine, a broad-spectrum phosphodiesterase inhibitor. It was further
      shown that an elevation of both ICa and cAMP (induced by isoprenaline), and not
      an increase of ICa alone (induced by Bay K 8644), is required to produce the
      extra component of reduction by frequency. It is concluded that Ca2+ entry
      results in feedback regulation of ICa, through the activation of Ca(2+)-dependent
      phosphodiesterase(s). This is important in the context of sympathetic
      stimulation, which produces the companion conditions of an elevated heart rate
      and increases in cAMP levels and Ca2+ entry.

PMID- 8537816
TI  - Specificity for block by saxitoxin and divalent cations at a residue which
      determines sensitivity of sodium channel subtypes to guanidinium toxins.
AB  - bTyrosine 401 of the skeletal muscle isoform (mu 1) of the rat muscle Na channel
      is an important determinant of high affinity block by tetrodotoxin (TTX) and
      saxitoxin (STX) in Na-channel isoforms. In mammalian heart Na channels, this
      residue is substituted by cysteine, which results in low affinity for TTX/STX and
      enhanced sensitivity to block by Zn2+ and Cd2+. In this study, we investigated
      the molecular basis for high affinity block of Na channels by STX and divalent
      cations by measuring inhibition of macroscopic Na+ current for a series of point
      mutations at residue Tyr401 of the rat mu 1 Na channel expressed in Xenopus
      oocytes. Substitution of Tyr401 by Gly, Ala, Ser, Cys, Asp, His, Trp, and Phe
      produced functional Na+ currents without major perturbation of gating or ionic
      selectivity. High affinity block by STX and neosaxitoxin (NEO) with Ki values in
      the range of 2.6-18 nM required Tyr, Phe, or Trp, suggestive of an interaction
      between an aromatic ring and a guanidinium group of the toxin. The Cys mutation
      resulted in a 7- and 23-fold enhancement of the dissociation rate of STX and NEO,
      respectively, corresponding to rapid toxin dissociation rates of cardiac Na
      channels. High affinity block by Zn2+ (Ki = 8-23 microM) required Cys, His, or
      Asp, three residues commonly found to coordinate directly with Zn2+ in
      metalloproteins. For the Cys mutant of mu 1 and also for the cardiac isoform Na
      channel (rh1) expressed in the L6 rat muscle cell line, inhibition of macroscopic
      Na+ conductance by Zn2+ reached a plateau at 85-90% inhibition, suggesting the
      presence of a substate current. The Asp mutant also displayed enhanced affinity
      for inhibition of conductance by Ca2+ (Ki = 0.3 mM vs approximately 40 mM in wild
      type), but block by Ca2+ was incomplete, saturating at approximately 69%
      inhibition. In contrast, Cd2+ completely blocked macroscopic current in the Cys
      mutant and the L6 cell line. These results imply that the magnitude of substate
      current depends on the particular residue at position 401 and the species of
      divalent cation. The His mutant also exhibited enhanced sensitivity to block by
      H+ with a pKa of approximately 7.5 for the His imidazole group. Our findings
      provide further evidence that residue 401 of mu 1 is located within the outer
      vestibule of the Na channel but external to the single-filing region for permeant
      ions.

PMID- 8537817
TI  - Alpha-adrenergic stimulation activates a calcium-sensitive chloride current in
      brown fat cells.
AB  - The first response of brown adipocytes to adrenergic stimulation is a rapid
      depolarizing conductance increase mediated by alpha-adrenergic receptors. We used
      patch recording techniques on cultured brown fat cells from neonatal rats to
      characterize this conductance. Measurements in perforated patch clamped cells
      showed that fast depolarizing responses were frequent in cells maintained in
      culture for 1 d or less, but were seen less often in cells cultured for longer
      periods. Ion substitution showed that the depolarization was due to a selective
      increase in membrane chloride permeability. The reversal potential for the
      depolarizing current in perforated patch clamped cells indicated that
      intracellular chloride concentrations were significantly higher than expected if
      chloride were passively distributed. The chloride conductance could be activated
      by increases in intracellular calcium, either by exposing intact cells to the
      ionophore A23187 or by using pipette solutions with free calcium levels of 0.2
      1.0 microM in whole-cell configuration. The chloride conductance did not increase
      monotonically with increases in intracellular calcium, and going whole cell with
      pipette-free calcium concentrations > or = 10 microM rapidly inactivated the
      current. The chloride currents ran down in whole-cell recordings using
      intracellular solutions of various compositions, and were absent in excised
      patches. These findings imply that cytoplasmic factors in addition to
      intracellular calcium are involved in regulation of the chloride conductance. The
      chloride currents could be blocked by niflumic acid or flufenamic acid with IC50s
      of 3 and 7 microM, or by higher concentrations of SITS (IC50 = 170 microM), DIDS
      (IC50 = 50 microM), or 9-anthracene carboxylic acid (IC50 = 80 microM). The
      chloride conductance activated in whole cell by intracellular calcium had the
      permeability sequence PNOS > PI > PBr > PCl >> Paspartate, measured from either
      reversal potentials or conductances. Instantaneous current-voltage relations for
      the calcium-activated chloride currents were linear in symmetric chloride
      solutions. Much of the current was time and voltage independent and active at all
      membrane potentials between -100 and +100 mV, but an additional component of
      variable amplitude showed time-dependent activation with depolarization. Volume
      sensitive chloride currents were also present in brown fat cells, but differed
      from the calcium-activated currents in that they responded to cell swelling,
      required intracellular ATP in whole-cell recordings, showed no sensitivity to
      intracellular or extracellular calcium levels, and were relatively resistant to
      block by niflumic and flufenamic acids. (ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8537818
TI  - Calcium release and its voltage dependence in frog cut muscle fibers equilibrated
      with 20 mM EGTA.
AB  - Sarcoplasmic reticulum (SR) Ca release was studied at 13-16 degrees C in cut
      fibers (sarcomere length, 3.4-3.9 microns) mounted in a double Vaseline-gap
      chamber. The amplitude and duration of the action-potential stimulated free [Ca]
      transient were reduced by equilibration with end-pool solutions that contained 20
      mM EGTA with 1.76 mM Ca and 0.63 mM phenol red, a maneuver that appeared to
      markedly reduce the amount of Ca complexed by troponin. A theoretical analysis
      shows that, under these conditions, the increase in myoplasmic free [Ca] is
      expected to be restricted to within a few hundred nanometers of the SR Ca release
      sites and to have a time course that essentially matches that of release.
      Furthermore, almost all of the Ca that is released from the SR is expected to be
      rapidly bound by EGTA and exchanged for protons with a 1:2 stoichiometry.
      Consequently, the time course of SR Ca release can be estimated by scaling the
      delta pH signal measured with phenol red by -beta/2. The value of beta, the
      buffering power of myoplasm, was determined in fibers equilibrated with a
      combination of EGTA, phenol red, and fura-2; its mean value was 22 mM/pH unit.
      The Ca content of the SR (expressed as myoplasmic concentration) was estimated
      from the total amount of Ca released by either a train of action potentials or a
      depleting voltage step; its mean value was 2,685 microM in the action-potential
      experiments and 2,544 microM in the voltage-clamp experiments. An action
      potential released, on average, 0.14 of the SR Ca content with a peak rate of
      release of approximately 5%/ms. A second action potential, elicited 20 ms later,
      released only 0.6 times as much Ca (expressed as a fraction of the SR content),
      probably because Ca inactivation of Ca release was produced by the first action
      potential. During a depolarizing voltage step to 60 mV, the rate of Ca release
      rapidly increased to a peak value of approximately 3%/ms and then decreased to a
      quasi-steady level that was only 0.6 times as large; this decrease was also
      probably due to Ca inactivation of Ca release. SR Ca release was studied with
      small step depolarizations that open no more than one SR Ca channel in 7,000 and
      increase the value of spatially averaged myoplasmic free [Ca] by only 0.2 nM.

PMID- 8537819
TI  - Calcium inactivation of calcium release in frog cut muscle fibers that contain
      millimolar EGTA or Fura-2.
AB  - Cut muscle fibers from Rana temporaria (sarcomere length, 3.4-4.2 microns) were
      mounted in a double Vaseline-gap chamber (14-15 degrees C) and equilibrated with
      end-pool solutions that contained 20 mM EGTA and 1.76 mM Ca. Sarcoplasmic
      reticulum (SR) Ca release was estimated from changes in pH (Pape, P. C., D.-S.
      Jong, and W.K. Chandler. 1995. Journal of General Physiology. 106:000-000).
      Although the amplitude and duration of the [Ca] transient, as well as its spatial
      spread from the release sites, are reduced by EGTA, SR Ca release elicited by
      either depolarizing voltage-clamp pulses or action potentials behaved in a manner
      consistent with Ca inactivation of Ca release. After a step depolarization to -20
      or 10 mV, the rate of SR Ca release, corrected for SR Ca depletion, reached a
      peak value within 5-15 ms and then rapidly decreased to a quasi-steady level that
      was about half the peak value; the time constant of the last half of the decrease
      was usually 2-4 ms. Immediately after an action potential or a 10-15 ms prepulse
      to -20 mV, the peak rate of SR Ca release elicited by a second stimulation, as
      well as the fractional amount of release, were substantially decreased. The
      rising phase of the rate of release was also reduced, suggesting that at least
      0.9 of the ability of the SR to release Ca had been inactivated by the first
      stimulation. There was little change in intramembranous charge movement,
      suggesting that the changes in SR Ca release were not caused by changes in its
      voltage activation. These effects of a first stimulation on the rate of SR Ca
      release elicited by a second stimulation recovered during repolarization to -90
      mV; the time constant of recovery was approximately 25 ms in the action-potential
      experiments and approximately 50 ms in the voltage-clamp experiments. Fura-2,
      which is able to bind Ca more rapidly than EGTA and hence reduce the amplitude of
      the [Ca] transient and its spatial spread from release sites by a greater amount,
      did not prevent Ca inactivation of Ca release, even at concentrations as large as
      6-8 mM. These effects of Ca inactivation of Ca release can be simulated by the
      three-state, two-step model proposed by Schneider, M. F., and B. J. Simon (1988,
      Journal of Physiology. 405:727-745), in which SR Ca channels function as a single
      uniform population of channels. (ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8537820
TI  - Transforming growth factor-beta-3 is mitogenic for rat retinal progenitor cells
      in vitro.
AB  - Recent data indicate that the process of neurogenesis in the mammalian central
      nervous system (CNS) may be regulated by peptide growth factors, such as
      epidermal growth factor, transforming growth factor-alpha, and acidic or basic
      fibroblast growth factor. We have investigated whether members of the
      transforming growth factor-beta (TGF beta) family also play a role in this
      process and have found that TGF beta-3 is mitogenic for embryonic rat retinal
      cells in vitro. We also show that TGF beta-3 stimulates production of retinal
      amacrine cells while photoreceptor production remains unchanged. These data
      demonstrate that TGF beta-3 can regulate cell proliferation in the CNS during
      development and can also influence commitment or differentiation, or both, of
      neural progenitor cells to particular retinal fates.

PMID- 8537821
TI  - Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain.
AB  - The fate of the anterior neural ridge was studied by following the relative
      movements of simultaneous spot applications of DiI and DiO from stage 15 through
      stage 45. These dye movements were mapped onto the neuroepithelium of the
      developing brain whose shape was gleaned from whole-mount in situs to neural cell
      adhesion molecule and dissections of the developing nervous system. The result is
      a model of the cell movements that drive the morphogenesis of the forebrain. The
      midanterior ridge moves inside and drops down along the most anterior wall of the
      neural tube. It then pushes forward a bit, rotates ventrally during forebrain
      flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The
      midanterior plate drops, forming the floor of the forebrain ventricle, and,
      keeping its place behind the ridge, it gives rise to the posterior hypothalamus
      or infundibulum. The midlateral anterior ridge slides into the lateral anterior
      wall of the neural tube and stretches laterally into the optic stalk and retina,
      and then rotates into a ventral position. The lateral anterior ridge converges to
      the most anterior part of the dorsal midline during neural tube closure, then
      rotates anteriorly, and gives rise to telencephalic structures. Whole-mount
      bromodeoxyuridine labeling at these stages showed that cell division is
      widespread and relatively uniform throughout the brain during the late neurula
      and early tailbud stages, but that during late tailbud stages cell division
      becomes restricted to specific proliferative zones. We conclude that the early
      morphogenesis of the brain is carried out largely by choreographed cell movements
      and that later morphogenesis depends on spatially restricted patterns of cell
      division.

PMID- 8537822
TI  - Evidence for glutamate-mediated activation of hippocampal neurons by glial
      calcium waves.
AB  - Communication from astrocytes to neurons has recently been reported by two
      laboratories, but different mechanisms were though to underlie glial calcium wave
      activation of associated neurons. Neuronal calcium elevation by glia observed in
      the present report is similar to that reported previously, where an increase in
      neuronal calcium was demonstrated in response to glial stimulation. In the
      present study hippocampal neurons plated on a confluent glial monolayer displayed
      a transient increase in intracellular calcium following a short delay after the
      passage of a wave of increased calcium in underlying glia. Activated cells
      displayed action potentials in response to glial waves and showed
      antineurofilament immunoreactivity. Finally, the N-methyl-D-aspartate glutamate
      receptor antagonist DL-2-amino-5-phosphonovaleric acid and the non-NMDA glutamate
      receptor antagonist 6,7-dinitroquinoxaline-2,3-dione significantly reduced the
      responsiveness of neurons to glial calcium waves. Our results indicate that
      hippocampal neurons growing on hippocampal or cortical astrocytes respond to
      glial calcium waves with elevations in calcium and increased electrical activity.
      Furthermore, we show that in most cases this communication appears to be mediated
      by ionotropic glutamate receptor channels.

PMID- 8537823
TI  - Human Schwann cells in vitro. I. Failure to differentiate and support neuronal
      health under co-culture conditions that promote full function of rodent cells.
AB  - Schwann cells (SCs) play critical roles in regeneration after injury to the
      peripheral nervous system and can also induce axonal regeneration in the central
      nervous system. Transplantation of purified SCs into sites of neural injury in
      rodents has confirmed the remarkable ability of these cells to promote axonal
      regrowth, suggesting that human application of SC transplantation could be
      valuable. In this report, we have compared the functional capacities of SCs
      derived from adult human and rodent nerves by of SCs derived from adult human and
      rodent nerves by maintaining SCs from these two sources in culture with sensory
      neurons. We noted that techniques commonly in use for maintaining pure rat SC
      populations are not sufficient to sustain populations of human SCs free of
      fibroblasts. In these co-cultures, human SCs express a limited profile of
      characteristic behaviors and they proliferate more slowly than rat SCs in
      response to axonal contact. Slow SC proliferation, relative to that of
      contaminating fibroblasts, leads to a high proportion of fibroblasts in the
      cultures. After 3 to 4 weeks of co-culture with neurons, human SCs express
      extracellular matrix molecules, but only partially ensheathe axons, whereas rat
      SCs differentiate, form basal lamina, and ensheathe or myelinate axons. Co
      culture of sensory neurons with human (but not rat) SC preparations (or
      conditioned medium therefrom) leads to a progressive neuronal atrophy
      characterized by shrinking neuronal cell bodies and a decrease in the density of
      the neurite network in the culture dish. As the divergent effects of human and
      rat SCs on neuronal health were also observed in co-cultures with human sensory
      neurons, these effects reflect differences between the rat and human-derived SC
      populations, rather than a species mismatch between SCs and neurons. The marked
      differences in behavior observed between rat and human SCs derived by the same
      methods requires further exploration if human-derived SCs are to be considered in
      the treatment of disease. In a companion article we report experiments that
      define culture conditions more effective in promoting human SC function in vitro.

PMID- 8537825
TI  - White-throated sparrow morphs that differ in song production rate also differ in
      the anatomy of some song-related brain areas.
AB  - White-throated sparrows are unusual among songbirds in that they occur in two
      color morphs, white-striped and tan-striped, determined by a chromosomal
      inversion and maintained by negative assortative mating. These differ in several
      reproductive behaviors, including amount of singing: white-striped males sing
      frequently, tan-striped females never sing, and tan-striped males and white
      striped females sing an intermediate amount. The present study measures the
      volumes of several nuclei in the avian song system and relates these to color
      morph and to sex. We find that robustus archistristalis and the tracheosyringeal
      part of the hypoglossal nucleus, nuclei closely involved in song production, are
      larger in white-striped than in tan-striped birds. We also find morph differences
      for nuclei in the rostral division of the song system, nuclei believed to be less
      directly involved in song production. We find sex differences throughout the song
      system as has been reported in other songbirds. Relationships between structure
      and function in the song system are discussed.

PMID- 8537824
TI  - Human Schwann cells in vitro. II. Myelination of sensory axons following
      extensive purification and heregulin-induced expansion.
AB  - Co-culture conditions are well established in which Schwann cells (SCs) derived
      from immature or adult rats proliferate and form myelin in response to contact
      with sensory axons. In a companion article, we report that populations of adult
      derived human Schwann cells (HASCs) fail to function under these co-culture
      conditions. Furthermore, we report progressive atrophy of neurons in co-cultures
      containing populations of either human fibroblasts or HASCs (which contain both
      SCs and fibroblasts). Two factors that might account for the insufficiency of the
      co-culture system to support HASC differentiation are the failure of many HASCs
      to proliferate and the influence of contaminating fibroblasts. To minimize
      fibroblast contamination of neuron-HASC co-cultures, we used fluorescence
      activated cell sorting to highly purify HASC populations (to more than 99.8%). To
      stimulate expansion of the HASC population, a mitogenic mixture of heregulin (HRG
      beta 1 amino acid residues 177-244; 10 nM), cholera toxin (100 ng/mL), and
      forskolin (1 microM) was used. When these purified and expanded HASCs were co
      cultured with embryo-derived rat sensory neurons, neuronal shrinkage did not
      occur and after 4 to 6 weeks some myelin segments were seen in living co
      cultures. This myelin was positively identified as human by immunostaining with a
      monoclonal antibody specific to the human peripheral myelin protein P0 (antibody
      592). Although this is the first reported observation of myelination by HASCs in
      tissue culture, it should be noted that myelination occurred more slowly and in
      much less abundance than in comparable cultures containing adult rat-derived SCs.
      We anticipate that further refinements of the HASC co-culture system that enhance
      myelin formation will provide insights into important aspects of human SC biology
      and provide new opportunities for studies of human peripheral neuropathies.

PMID- 8537826
TI  - Scutoid mutation of Drosophila melanogaster specifically decreases olfactory
      responses to short-chain acetate esters and ketones.
AB  - A molecular-genetic approach has been taken to identify genes involved in
      olfactory transduction in Drosophila melanogaster. Two independent lines of
      research led to the finding that the dominant Scutoid (Sco) mutation causes a
      diminished extracellular electroantennogram response to the odorants ethyl
      acetate (EtAC) and acetone (AC). Sco flies showed about 4- and 2.5-fold reduced
      responses to EtAC and AC, respectively, compared to Canton-S wild-type and
      sibling control flies lacking the Sco mutation when electroantennogram recordings
      were made from the proximal anterior third antennal segment. The responses to
      five other odors from three different chemical classes were unaltered. The
      maximum response to either EtAC or AC was decreased with no change in apparent
      affinity. Responses to short-chain (but not long-chain) acetate esters and
      ketones were dramatically affected at all antennal locations tested. Only in the
      proximal quadrants were responses to ethyl acetoacetate also reduced. Most Sco
      revertants tested had a normal olfactory response; duplications of the region
      including no-ocelli partially suppress the Sco bristle as well as olfactory
      phenotypes. Sco adults had an impaired behavioral response to EtAC but not to
      banana or propionate. There was no effect of the mutation on larval chemosensory
      behavior or extracellularly recorded adult compound eye and ocellar visual
      responses. These findings suggest the involvement of Sco in an olfactory pathway
      in adults which is specific for short-chain acetate esters and ketones.

PMID- 8537827
TI  - 20-Hydroxyecdysone stimulates proliferation of glial cells in the developing
      brain of the moth Manduca sexta.
AB  - The steroid hormone 20-hydroxyecdysone (20-HE) controls diverse aspects of
      neuronal differentiation during metamorphosis in the hawkmoth Manduca sexta. In
      the present study we have examined the effect of 20-HE on glial cells of the
      brain during the metamorphic period. The antennal (olfactory) lobe of Manduca
      provides an ideal system in which to study effects of hormones on glial cells,
      since three known classes of glial cells participate in its development, and at
      least one type is critically important for establishment of normal neuronal
      morphology. These glial cells, associated with the neuropil, form boundaries for
      developing olfactory glomeruli as a result of proliferation and migration. We
      determined whether glial cells proliferate in response to 20-HE by injecting a
      pulse of 20-HE into the hemolymph at different stages of development and
      monitoring proliferation of all three types of glial cells. Hormone injections at
      the beginning and end of metamorphic development, when hormone titers are
      normally low, did not stimulate proliferation of neuropil-associated glial cells.
      Injections during the period when hormone titers are normally rising produced
      significant increases in their proliferation. Injections when hormone titers are
      normally high were ineffective at enhancing their proliferation. One other class
      of glial cells, the perineurial cells, also proliferate in response to 20-HE.
      Thus, glial proliferation in the brain is under the control of steroid hormones
      during metamorphic development.

PMID- 8537828
TI  - Development of an identified serotonergic neuron in the antennal lobe of the moth
      and effects of reduction in serotonin during construction of olfactory glomeruli.
AB  - Each olfactory (antennal) lobe of the moth Manduca sexta contains a single
      serotonin (5-HT) immunoreactive neuron whose processes form tufted arbors in the
      olfactory glomeruli. To extend our present understanding of the intercellular
      interactions involved in glomerulus development to the level of an individual,
      identified antennal lobe neuron, we first studied the morphological development
      of the 5-HT neuron in the presence and absence of receptor axons. Development of
      the neuron's glomerular tufts depends, as it does in the case of other
      multiglomerular neurons, on the presence of receptor axons. Processes of the 5-HT
      neuron are excluded from the region in which the initial steps of glomerulus
      construction occur and thus cannot provide a physical scaffolding on which the
      array of glomeruli is organized. Because the neuron's processes are present in
      the antennal lobe neuropil throughout postembryonic development, 5-HT could
      provide signals that influence the pattern of development in the lobe. By
      surgically producing 5-HT-depleted antennal lobes, we also tested the importance
      of 5-HT in the construction of olfactory glomeruli. Even in the apparent absence
      of 5-HT, the glomerular array initiated by the receptor axons was histologically
      normal, glial cells migrated to form glomerular borders, and receptor axons
      formed terminal branches in their normal region within each glomerulus. In some
      cases, 5-HT-immunoreactive processes from abnormal sources entered the lobe and
      formed the tufted intraglomerular branches typical of most antennal lobe neurons,
      suggesting that local cues strongly influence the branching patterns of
      developing antennal lobe neurons.

PMID- 8537829
TI  - Assessment of postdischarge concerns of coronary artery bypass graft patients.
AB  - Cardiac surgery patients are currently being discharged from hospitals earlier
      than ever before. Problems experienced by these patients after discharge are less
      well documented in the literature than are predischarge problems. Understanding
      the nature of patients' concerns about their recovery at home can help clinicians
      plan interventions to alleviate those concerns. This study documents the nature
      of patients' concerns after discharge home. Data were collected over a 3-year
      period using a 24-hour telephone contact system. Of 356 coronary artery bypass
      graft surgery patients discharged, 196 made 392 telephone calls regarding 445
      concerns. These concerns were recorded systematically and analyzed for patterns
      of commonality. Patients' primary concerns were related to leg incision healing,
      pain, leg swelling, and medications. Recommendations for discharge planning are
      discussed.

PMID- 8537830
TI  - Risk profile screening.
AB  - The recovery period following hospitalization for a CHD event is an ideal time to
      assess a patient for risk factors and to offer intervention. Frequently, the
      nurse is the single source of such care and has opportunity to educate the
      patient and offer suggestions for life-style modifications that can reduce the
      recurrence of CHD events. This article describes modifiable risk factors and
      methods of assessment, cites sources for management and general health screening
      method, that can provide a comprehensive assessment of health risks. Gender or
      ethnic-specific issues, have been highlighted. A very brief mention of age
      specific risk factors is included.

PMID- 8537831
TI  - Assessment of the cardiovascular effects of stress.
AB  - The stress response increases sympathetic nervous activity, which can adversely
      affect the cardiovascular system. Cardiovascular disease is due in part to stress
      induced mechanisms mediated primarily through increased adrenergic stimulation.
      These stress-induced mechanisms include elevations in serum lipid levels,
      alterations in blood coagulation, atherogenesis, vascular changes in
      hypertension, and myocardial ischemia. Stress management interventions for
      hypertension are controversial; however, interventions for coronary heart disease
      prone behavior patterns have proven successful. Stress management interventions
      have also reduced cardiovascular events, mortality, and coronary atherosclerosis.
      Assessment of stress includes individual interviews, which can be complemented by
      information derived from questionnaires and mental stress testing. Educational
      and relaxation strategies can prepare patients to understand and cope with
      stress. These approaches will hopefully decrease the occurrence of stress and,
      ultimately, the risk for cardiovascular disease.

PMID- 8537832
TI  - Drug profiles: maximizing therapeutic effectiveness.
AB  - Major cardiac events are inevitably followed with a pharmacologic plan of therapy
      for cardiac patients. Careful assessment of the patient's drug regimen is an
      important aspect of cardiovascular nursing practice. Such assessment will reveal
      implications for education, compliance counseling, and side effect evaluation. A
      thorough drug history should include information about both prescription and
      nonprescription drug use. Assessment for adherence is improved by using
      supportive, open-ended questions. Assessment for side effects that affect quality
      of life is important, particularly in the area of sexual dysfunction. Sexual
      function should be assessed before beginning cardiovascular drug therapy and
      monitored for changes during treatment. Using principles of chronopharmacology,
      or therapy based on the time-dependent effects of drugs, nurses can schedule
      cardiovascular medications and evaluate patient responses in relation to
      circadian variability in vulnerability and symptoms. Assessment for ease of self
      management of the drug regimen should be a particular focus with non-English
      speaking patients and those with complex or costly drug regimens.

PMID- 8537833
TI  - Assessing social support in patients with cardiac disease.
AB  - An increasingly large body of literature demonstrates the positive effects of
      social support for patients with all illnesses and cardiovascular disease in
      particular. However, social support is not the same, nor is it equally beneficial
      in all circumstances. This article reviews key aspects of the social support
      literature and presents a model for assessing social networks.

PMID- 8537834
TI  - Diagnostic and functional exercise testing: test selection and interpretation.
AB  - Exercise stress tests are useful in many areas of medical practice and research.
      The results extend the clinical significance of information obtained from other
      sources (ie, detailed history, thorough physical examination, resting
      electrocardiogram, chest radiograph, and basic laboratory analyses) and serve as
      a diagnostic, prognostic, and therapeutic guide. Leg or arm ergometry is commonly
      used to assess a patient's functional status, diagnose relative myocardial
      ischemia, and investigate physiologic mechanisms of cardiac symptoms. The
      responses may also be used to determine the effects of interventions such as
      coronary artery bypass surgery, percutaneous transluminal coronary angioplasty,
      medications, or exercise training.

PMID- 8537835
TI  - Sexual counseling of MI patients by cardiac nurses.
AB  - This study examined the assessment of sexual concerns and the practice of sexual
      counseling with myocardial infarction patients in a convenience sample of 171
      cardiac nurses from three hospitals in the Midwest. Seventy-five percent of
      nurses (n = 129) had offered to discuss sexual concerns with less than 2% of
      their clients in the preceding year, and 71% of nurses (n = 122) had never
      referred clients for sexual counseling to another professional. Analysis of 17
      items on the practice index indicated that nurses are not assessing sexual
      concerns, and specific information relevant to myocardial infarction patients
      largely is not being taught.

PMID- 8537836
TI  - Assessment of quality of life in recovery settings.
AB  - Quality of life is a construct of intense interest to researchers and clinicians
      and is especially important with cardiovascular patients in recovery settings
      where the goal of care is to return the patient to a life style not diminished by
      illness or treatment. This article presents a discussion of a number of issues
      related to assessment of quality of life in recovery settings, including
      definition and dimensions of the construct, measurement, and design. Model
      development and testing is recommended as a crucial step in increasing the
      understanding of quality of life in this patient population.

PMID- 8537837
TI  - The complications and difficulties of management of nonunion in the severely
      obese.
AB  - Operative fixation of 22 nonunited fractures was undertaken in 21 obese patients.
      Eleven patients were women and 10 were men, with an average age of 46.3 years
      (range 25-74). The average body mass index in this group of patients was 37.9
      kg/m2 (range 33.2-57.1). Two patients were classified as morbidly obese and 19 as
      severely obese. The management of these patients proved to be fraught with
      difficulties related to their obesity. There were a number of occurrences
      believed to be related to poorly protective positioning and prolonged ischemic
      pressure under the patient's body weight during the administration of anesthetic,
      including a peroneal compartment syndrome, a gluteal compartment syndrome with
      sciatic nerve palsy, bilateral brachial plexus stretch injuries, an anterior
      interosseous nerve palsy, and the postoperative development of a patch of scalp
      alopecia. There were two wound separations and no episodes of thromboembolic
      disease. Sixteen nonunited fractures healed after the index procedure at an
      average time to healing of 5.6 months (range 2-14). Five nonunited fractures
      required a second procedure to gain union [average total time to healing 17
      months (range 10-31)]. A single fracture remains ununited. Awareness of the
      unique technical demands and operative and anesthetic risks encountered when
      undertaking an operative procedure in a severely obese patient is imperative for
      the safe and successful treatment of orthopaedic surgical problems in these
      patients.

PMID- 8537838
TI  - Major open injuries of the talus.
AB  - Seventeen patients with 18 open talar fracture-dislocations or total dislocations
      of the talus were reviewed to determine the functional outcome and incidence of
      infection. Seven of 18 feet (38%) developed infection. Infection was associated
      with extrusion of the talar body through the open wound (p < 0.025). Final follow
      up was achieved in 13 of 17 patients (14 of 18 feet) at an average of 7 years and
      4 months after injury. According to the Boston Children's Hospital ankle grading
      system, the overall results were considered excellent in one, good in five, fair
      in two, and failures in six feet. The data suggest a greater proportion of
      failures in the infected group compared with the non-infected group (p = 0.05).

PMID- 8537839
TI  - Early versus delayed treatment of severe ankle fractures: a comparison of
      results.
AB  - A retrospective review of 202 closed Weber B bimalleolar or bimalleolar
      equivalent ankle fractures treated using open reduction and internal fixation
      (ORIF) from January 1, 1991, through January 1, 1994 was completed at our
      institution. A total of 105 ankles (52%) were treated using ORIF within 5 days of
      injury (early group), with a mean 1.5 days from injury to surgery. A total of 97
      ankles (48%) were treated after 5 days (delayed group), with a mean of 13.6 days
      from injury to surgery. Operative time, length of hospital stay, postoperative
      range of motion, adequacy of reduction, wound and other complications, and other
      sequelae were compared between the two groups. No significant difference in range
      of motion at latest follow-up or in operative time was evident between the
      groups. Minor wound complications were present in 4.8% of the early group
      compared with 6.2% in the delayed group. No deep infections or osteomyelitis were
      present in either group. Anatomic reductions were present in 89% and poor
      reductions (> 2 mm displacement) in 1% of those ankles treated within 5 days
      versus 83% anatomic reductions and 3% poor reductions in those treated after 5
      days. The differences in wound complications and anatomic reductions between
      groups was not statistically significant. There was a significantly longer median
      hospital stay in the early (3 days) versus delayed groups (2 days). We conclude
      that the results and complications of early versus delayed treatment is not
      significantly different, except for a shorter median hospital stay in the delayed
      group. Delayed ORIF is an acceptable alternative when soft-tissue swelling,
      fracture blisters, or abrasions are present that offer an undesirable environment
      for surgical incisions. Using contemporary, a traumatic techniques, delayed
      surgery can provide anatomic reduction with minimal complications in severe ankle
      fractures.

PMID- 8537840
TI  - A biomechanical study of three wiring techniques for cerclage-plating.
AB  - Transverse fractures at the distal tip of a well-fixed femoral prosthesis are
      difficult to stabilize using plates and screws due to the presence of the
      underlying intramedullary stem. The attachment of plates using cerclage wires
      obviates the need for screws, but the stability provided by cerclage plating is a
      clinical concern. In this study we compared the mechanical performance of three
      wire-cerclage plating techniques: (a) simple cerclage (each wire wrapped around
      the bone and plate once); (b) double cerclage (each wire wrapped around the bone
      and plate twice); and (c) a new method that used small stainless steel inserts
      that fit into the plate holes and permit the direct coupling of the cerclage
      wires to the plate. To compare the performance of the three fixation constructs,
      synthetic femora were osteotomized, stabilized with a wire cerclage plating
      technique, and subjected to monotonic and cyclic loading using a Materials
      Testing System (Minneapolis, MN) servo-hydraulic testing system. The performance
      of each construct was evaluated using seven different mechanical parameters (four
      monotonic, three cyclic). Double cerclage performed significantly better than did
      simple cerclage for three of the seven mechanical parameters. The insert
      technique performed significantly better than did the simple and double cerclage
      techniques for all seven of the measured mechanical parameters. For both
      monotonic and cyclic loading, the use of inserts resulted in an improvement in
      fixation strength and stability in comparison with conventional simple and double
      cerclage plating techniques. The insert technique shows promise in the treatment
      of this difficult type of fracture at the distal tip of a well-fixed femoral
      prosthesis.

PMID- 8537841
TI  - Is computed tomography useful after simple posterior hip dislocation?
AB  - Recent articles and textbooks of orthopaedic traumatology recommend routine
      computed tomography (CT) scans after successful reduction of simple posterior hip
      dislocations. This is based on the belief that CT, even in cases with concentric
      reductions, may identify fractures or intraarticular loose bodies not apparent on
      standard radiographs. This study was conducted to assess the usefulness of CT
      after concentric reduction of simple posterior hip dislocations. The hospital
      database was searched for all traumatic hip dislocations in the past 4 years.
      Charts and radiographs were reviewed, and only patients with simple posterior hip
      dislocations (no acetabular or femoral head fractures) and a concentric reduction
      identified on plain radiographs were included. Twenty-three patients who met
      these criteria and had subsequent CT scans to evaluate the hip joint were
      identified. CT scans confirmed the concentric reduction in all patients. Three
      small occult fractures were identified, and no occult intraarticular loose bodies
      were found. CT findings did not alter the treatment plan for any of the patients
      studied. In this small group of patients, CT scanning was not useful after
      concentric reduction by plain radiography of simple posterior hip dislocations.

PMID- 8537842
TI  - Effect of nonsteroidal antiinflammatory drugs on fracture healing: a laboratory
      study in rats.
AB  - We studied the effects of two nonsteroidal antiinflammatory drugs (NSAIDs) on
      fracture healing in rats: ibuprofen (30 mg/kg/day) and indomethacin (1
      mg/kg/day). Femoral fractures were induced via a three-point bending technique.
      NSAIDs were administered orally for 4 or 12 weeks. Control animals received no
      medication. In each group a minimum of six animals were killed at the following
      intervals: 2, 4, 6, 8, 10, and 12 weeks postfracture. Fracture healing was
      determined by mechanical testing and histologic evaluation. The bending strength
      of each fractured femur was expressed as a percentage of the strength of the
      intact, contralateral femur. Histologic evaluation was performed on serial
      longitudinal sections stained with hematoxylin and eosin using a qualitative
      score of maturity of the callus. Ibuprofen and indomethacin both retarded
      fracture healing, with significant differences in "mechanical healing" found
      between the control and experimental groups after 10 weeks of drug
      administration. Both drugs also induced qualitative histologic changes manifested
      by delayed maturation of callus, which was noticeable earlier than the difference
      found by mechanical testing of bone. Our data suggest that NSAIDs have an
      inhibitory effect on fracture repair that is reversible after cessation of
      indomethacin but not ibuprofen.

PMID- 8537843
TI  - Bone toxicity of locally applied aminoglycosides.
AB  - The effect of tobramycin on osteoblasts was studied. Osteoblast-like cells from
      the MG-63 human osteosarcoma cell line were grown in antibiotic-free media and
      exposed to concentrations of tobramycin: first at order of magnitude intervals
      between 0 and 10,000 micrograms/ml, and then at closer intervals between 100 and
      1,000 micrograms/ml to more accurately define toxic levels. Cell number and 3H
      thymidine incorporation at 0, 24 and 72 h were determined. Similarly, primary
      cultures of rat osteoblasts were exposed to the same concentrations of tobramycin
      to confirm the validity of the MG-63 cell line as a model for nontransformed
      cells. The results of this study demonstrate that local levels of tobramycin of <
      or = 200 micrograms/ml have little or no effect on osteoblast replication.
      Concentrations of 400 micrograms/ml significantly decreased cell replication, and
      concentrations of 10,000 micrograms/ml caused cell death. Results obtained with
      primary rat osteoblast cultures were similar to those obtained from the MG-63
      cultures at the tested tobramycin concentrations.

PMID- 8537844
TI  - Reduction of forearm fractures in children using axillary block anesthesia.
AB  - One hundred eleven patients (age range 15 months-16 years, mean 9.6 years) with
      displaced forearm fractures who had axillary blocks performed by orthopaedists in
      the emergency room were retrospectively reviewed. Thirty-seven fractures involved
      the distal radius, 56 involved both bones of the forearm, and 12 involved the
      physis of the distal forearm. Three Monteggia fractures, one radial neck
      fracture, one olecranon with an associated radial neck fracture, and one distal
      radius fracture with an associated elbow dislocation also were included. Of the
      111 axillary blocks, 105 were rated as effective. Potential complications of
      axillary block anesthesia (systemic toxicity, hematoma, infection, and brachial
      neuralgia) were not observed in this group of patients. The cost of axillary
      block reduction in the emergency room was less than one third that of general
      anesthesia in the operating room. Axillary block anesthesia is reliable, safe,
      and cost effective, and this study supports its use by orthopaedists in displaced
      forearm fractures in children.

PMID- 8537845
TI  - Delayed onset of forearm compartment syndrome: a complication of distal radius
      fracture in young adults.
AB  - The signs and symptoms of elevated intracompartmental pressure in the volar
      forearm compartment developed on a delayed basis (range 18-54 h) in the absence
      of constricting casts or dressings in eight limbs after high-energy
      intraarticular fractures of the distal end of the radius. Intracompartment
      pressures averaged 80 mm Hg in the six limbs tested. Despite urgent decompression
      and fracture fixation with delayed wound closure, final functional outcomes were
      compromised in seven cases, reflecting the severity of the articular injuries,
      and poor in one case, in which a wrist fusion was later required. If potentially
      serious complications are to be prevented, careful observation of these patients,
      often for periods of 48 h, is important. Selective recording of forearm
      intracompartmental pressures may be advised in at-risk patients.

PMID- 8537846
TI  - Composite bone grafting and plate fixation for the treatment of nonunions of the
      forearm with segmental bone loss: a report of eight cases.
AB  - Between June 1986 and December 1991, eight aseptic isolated severe forearm
      segmental bone losses were treated. The average age of the patients was 26 years.
      Three cases involved the radius and five the ulna. The average time between the
      onset of trauma and the final surgical intervention was 9 months. The surgical
      technique consisted of complete removal of necrotic bone, filling of the bone
      defect with an intercalary autogenous bone graft, and stable internal fixation,
      which required combining a plate and an opposite cortical bone allograft. The
      average bone loss length after freshening the bone ends was 7 cm (range 4-11).
      The average follow-up was 48 months (range 24-80). In all eight cases union and
      recovery of forearm function was achieved. The proposed surgical technique proved
      to be effective in obtaining results with no major complications.

PMID- 8537847
TI  - Iatrogenic posterior interosseous nerve injury: is transosseous static locked
      nailing of the radius feasible?
AB  - To assess the risk of injury to the posterior interosseous nerve (PIN) in
      transosseous locked nailing of the radius, the relationship of the PIN to the
      surgical zone was studied in five pairs of fresh frozen adult cadaver arms. A
      static locked intramedullary nail was inserted in each radius using the
      recommended surgical technique. A formal dissection of the radial nerve and its
      branches was then performed to document the relationship of the PIN to the radial
      head in neutral, pronation, and supination also was measured. In no specimens was
      the PIN injured by the screw insertion. However, in two specimens (right and left
      arm of the same donor) the PIN was 1 mm and 2 mm, respectively, from the screw
      insertion site. The average shortest distance from the PIN to the screw was 11.3
      mm. As measured along the mid-shaft of the radius, the average distance from the
      radial head to the PIN was 36.2 mm in 90 degrees supination, 46.7 mm in neutral,
      and 56.9 mm in 90 degrees pronation. Transosseous static locked nailing of the
      radius is feasible, but the surgeon and patient must be aware of the risk of
      possible injury to the PIN. To minimize this risk, we suggest that the proximal
      locking screw should be inserted from a direct lateral entry at < 30 mm from the
      radial head with the forearm in neutral rotation.

PMID- 8537848
TI  - Closed reduction and percutaneous pinning of displaced supracondylar humerus
      fractures in children: description of a new closed reduction technique for
      fractures with brachialis muscle entrapment.
AB  - A retrospective review of 43 displaced extension-type supracondylar humerus
      fractures in children was performed. Thirty-four fractures were completely
      displaced (type III). Ninety-one percent (39 of 43) of the fractures were managed
      by immediate closed reduction and percutaneous pinning. Ten type III fractures
      exhibited clinical or radiographic evidence of brachialis muscle penetration. A
      closed reduction maneuver designed to "milk" the entrapped brachialis muscle off
      of the proximal fracture spike was developed and was successful in all eight
      cases in which it was attempted. At mean follow-up of 35 months, 97% (38 of 39
      patients) achieved a good or excellent result based on the Flynn grading scale.

PMID- 8537849
TI  - Analysis of tardy ulnar nerve palsy associated with cubitus varus deformity after
      a supracondylar fracture of the humerus: a report of four cases.
AB  - Four cases of tardy ulnar nerve palsy associated with a cubitus varus deformity
      of the elbow secondary to a supracondylar fracture of the humerus are presented.
      All patients had surgical management of their ulnar nerve palsy. In two patients,
      the ulnar nerve was entrapped by scar tissue at the abnormal position and the
      nerve developed a sharp V-shaped kink when the elbow was flexed. In one patient,
      the ulnar nerve displaced anteriorly with elbow flexion and spontaneously reduced
      into the ulnar nerve groove with elbow extension. In one patient, the ulnar nerve
      remained in the ulnar nerve groove; however, it was entrapped by fibrous bands
      arising from the flexor carpi ulnaris. It is speculated that malunion resulting
      in cubitus varus deformity will alter the anatomy at the elbow and that this can
      have a direct effect on the position and instability of the ulnar nerve.
      Incongruity of the elbow joint due to cubitus varus deformity also may cause
      osteoarthritis changes. As a result, ulnar neuropathy may develop from irritation
      to the ulnar nerve from the posttraumatic osteoarthritic changes at the elbow
      joint.

PMID- 8537850
TI  - Traumatic anterior dislocation of the radial head in an adult.
AB  - We report an isolated anterior dislocation of the radial head in an adult after
      sustaining a fall on the outstretched arm. Based on history and presentation, we
      speculate that the injury occurred in a position of hyperextension and
      supination. Reduction was achieved by a pronation maneuver.

PMID- 8537851
TI  - Neurovascular injury as a complication of subclavicular migration of a fractured
      humeral head: a case report and review of the literature.

PMID- 8537852
TI  - Lower leg fracture with Parkes-Weber syndrome complicated by disseminated
      intravascular coagulation.
AB  - Reports of Parkes-Weber syndrome complicated by disseminated intravascular
      coagulation (DIC) are rare in the orthopaedic literature. This is a case report
      of a 23-year-old man who had this syndrome and who sustained a lower-leg fracture
      complicated by the DIC. Open reduction was not attempted because the DIC worsened
      after manual reduction. Amputation was rejected by the patient. Three months of
      continuous infusion of heparin and replacement therapy with fresh frozen plasma
      was done. Cast immobilization without further reductions was continued. The DIC
      improved and union of the fractures was observed at 2 years and 3 months after
      injury.

PMID- 8537854
TI  - Ultrasonographic growth measurements in triplet pregnancies.
AB  - The incidence of triplet pregnancies is increasing due to the widespread use of
      ovulation induction agents and assisted conception treatments. The aim of this
      study was to acertain the normal ultrasonographic measurements for fetal growth
      parameters in triplet pregnancies. The ultrasonographic measurements of all
      triplet pregnancies managed in two major hospital centres were reviewed
      retrospectively and those in which there was less than 25% discordance in birth
      weight were included in the study. Triplet 50th centile for fetal biparietal
      diameter, whilst falling through the normal singleton centile range from 27 weeks
      gestation, did not fall below the 10th centile value of singletons. Triplet 50th
      centile for head circumference was equivalent to the singleton 10th centile from
      23 weeks gestation. Triplet 50th centile for abdominal curcumference was
      persistently below that of the singleton 50th centile, falling below the
      singleton 10th centile from 29 weeks gestation. Normal growth rate of triplet
      gestations in the third trimester of pregnancy varies from that of singletons. An
      awareness of this altered growth rate is necessary to avoid the inappropriate
      diagnosis of asymmetrical triplet fetal growth retardation. We suggest that the
      growth curves presented here may be used to monitor triplet fetal growth.

PMID- 8537853
TI  - Acid-base changes after severe birth acidaemia.
AB  - The aim of this study was to assess prospectively acid-base changes after severe
      birth acidaemia. Fourty-five term babies with severe acidaemia (median umbilical
      artery pH 6.99 [Range 6.74-7.05], mean base deficit 16.3 [SD 3.7] mmol/l) were
      prospectively identified. Pathological cardiotocographs were present in 32 (71%)
      prior to delivery and 39 (87%) were delivered operatively; 27 for fetal distress.
      Sixteen required intubation. At one hour of age, median pH was 7.29 [Range 7.04
      7.45] and the change in pH correlated with one hour pCO2 (r = 0.62 p < 0.001). pH
      measurements were obtained in 11 of the 16 babies with a 1 hour pH < or = 7.25
      and all values had recovered by this time. Five of this group were receiving
      oxygen. Of the 11 babies admitted to NICU, 1 died and 3 had evidence of
      encephalopathy, all of which were normal at follow-up [2-12 months]. Recovery of
      pH after severe birth acidaemia was evident at 1 hour of age and would appear to
      be complete by 4 hours.

PMID- 8537856
TI  - The changes of maternal deaths in Japan.
AB  - Maternal deaths in Japan are compared and discussed with those of highly
      developed countries. It is still higher in this country than in other highly
      developed ones, and we think it is necessary to furnish the tertially emergency
      hospitals and maternal transfer system.

PMID- 8537855
TI  - Sex ratio in triplets.
AB  - Since the introduction of different ovulation induction regimens the incidence of
      triplet pregnancies increased from a spontaneous rate of about 1:10,000 to the
      frequency of nearly 1:1000. Sex ratio of trigemini and male/female proportion of
      the three newborns within the same triplet set is the amazing issue that we
      attempted to elucidate in the present study. Data on 36 women with triplet
      pregnancies delivered in our hospital and information regarding 2717 triplet
      pregnancies reported by 16 relevant papers were included in this study. 36 women
      delivered 63 (58%) male and 45 (42%) female babies. Triplet sets of same gender
      comprised 33% of all trigemini. Sex ratios (male/female) for the spontaneous,
      menotropin and clomiphene group were 2.00, 1.57 and 0.94 respectively. Homogenous
      male/female set ratio was 5.0, 2.0 and 0.5 in menotropin, spontaneous and
      clomiphene groups respectively. As the percentage of ovulation induction triplet
      pregnancies increased constantly from 0% to 100%, a decline in the fraction of
      homogenous gender triplet sets was observed--from 73% to 23%. It may be concluded
      that sex ratio in triplet newborns is divergent according to different
      publications with most of the authors reporting a male/female ratio of less than
      1.00. Ovulation induction results in a lower proportion of homogenous sex
      triplets sets. Superovulation by menotropins cause a higher percentage of male
      triplet newborns when compared to ovulation induction by clomiphene.

PMID- 8537857
TI  - Umbilical cord fluoride serum levels may not reflect fetal fluoride status.
AB  - OBJECTIVE: To evaluate the reliability of fluoride levels in the umbilical cord
      as reflecting neonate fluoride status. DESIGN: Prospective study of fluoride
      levels of pregnant women at term and their neonates. SETTING: Delivery room and
      maternity unite of Hadassah Hospital Mount Scopus. PATIENTS: Fluoride serum
      levels were determined in the sera of 20 women with normal pregnancies at term,
      during delivery, in the corresponding mixed cord sera and neonatal sera at 24
      hours after delivery. RESULTS: The mean maternal fluoride serum level was 0.0303
      microgram/ml (SD 9.015), mean cord fluoride serum level 0.0183 microgram/ml (SD
      0.012), and mean neonatal fluoride serum 0.0380 microgram/ml (SD 0.016).
      CONCLUSION: The significantly (p < 0.001) low mixed cord serum levels of fluoride
      as compared with neonatal and maternal serum levels may be explained by placental
      sequestration of fluoride. It is suggested that cord serum fluoride levels to not
      reflect fetal fluoride status.

PMID- 8537858
TI  - First trimester diagnosis of cystic hygromata using transvaginal ultrasound and
      cytogenetic evaluation.
AB  - We studied the outcome of fetuses in whom cystic hygroma was diagnosed in the
      first and early second-trimester of pregnancy using transvaginal ultrasonography.
      The purpose of this study was to evaluate the association between fetal cystic
      hygroma and fetal cytogenetic abnormalities, and the long-term prognosis. Thirty
      five consecutive fetuses between 9.1 and 13.4 weeks of gestation diagnosed as
      having a nuchal hygroma were evaluated ultrasonographically and karyotyped. Those
      with a normal chromosome complement were ultrasonographically monitored
      throughout the remainder of the pregnancy to document the resolution of the
      hygroma. Eighteen of thirty-five fetuses were found to have a normal karyotype
      and five of these were aborted electively. The hygromas resolved in ten of these
      karyotypically normal fetuses within four weeks of initial diagnosis and they
      were phenotypically normal at birth. Seventeen fetuses were karyotypically
      abnormal with trisomy twenty-one being the most common abnormality. Prenatal
      cytogenetic analysis should be offered to women with fetal cystic hygroma
      diagnosed in the first trimester. A normal outcome is likely in those without
      chromosome abnormalities.

PMID- 8537859
TI  - Cytolytic action of stored human milk on blood cells in vitro.
AB  - Stored human milk induced cytolysis on various types of blood cells depending on
      the storage time and temperature. When separated by centrifugation after storage
      for 24 h at 4 degrees C, the cream, not whey, induced cytolysis. When separated
      and heated for 30 min at 56 degrees C before storage, neither cream or whey
      induced cytolysis. When the cream was heated at 56 degrees C for 30 min and mixed
      with non-heat-treated whey before being storage for 24 h at 4 degrees C, it
      induced cytolysis. When bile salt was added to whole milk before storage, the
      cytolytic activity was enhanced. When eserine was added, the cytolytic activity
      was suppressed. Thin layer chromatography showed that stored milk, not fresh
      milk, contained free fatty acids which caused a similar degree of cytolysis as
      stored whole milk. These results indicated that the cytolysis is due to the free
      fatty acids which were produced from triglycerides catalyzed by the lipase in
      milk.

PMID- 8537860
TI  - Erythrocyte deformability of nonpregnant, pregnant, and fetal blood.
AB  - Erythrocyte deformability is an important determinant of microcirculation, of
      oxygen transport and release to the tissue. In an attempt to clarify the
      rheological peculiarity during pregnancy, erythrocyte deformability was measured
      in 10 nonpregnant controls and 10 pairs of mothers and newborns. When the
      hematocrit of the erythrocyte suspension in dextran solution was adjusted to 35%,
      the deformability of fetal erythrocytes was significantly higher than maternal
      blood (P < 0.05), and it was almost similar to that of nonpregnant controls.
      Erythrocyte deformability was dependent on the hematocrit, and there was an
      optimal hematocrit value at which the deformability was maximal. The hematocrit,
      where the deformability was maximal, was a lower value (32-35%) in maternal
      blood, conversely, a higher value (47-50%) in cord blood than that (40-43%) in
      the nonpregnant. Despite decreased deformability of maternal erythrocytes, it may
      be compensated by reducing the hematocrit (hemodilution), preserving effective
      peripheral circulation including uteroplacental perfusion. On the other hand, the
      deformability of fetal erythrocytes may be higher in vivo at the hematocrit of 47
      50% to supply oxygen to the fetal tissue even in a low oxygen condition.

PMID- 8537861
TI  - Vasopressin, atrial natriuretic factor and renal water homeostasis in premature
      newborn infants with respiratory distress syndrome.
AB  - Arginine vasopressin (AVP), human atrial natriuretic peptide (hANP), and body
      fluid and electrolyte balance were examined during the first five days of life in
      eleven premature infants (birthweight 1610 +/- 240 g, gestation 30 +/- 1 weeks)
      receiving mechanical ventilation for respiratory distress syndrome (RDS). Plasma
      hANP and urine AVP concentrations were determined by radioimmunoassay on the
      first, third and fifth days. Arginine vasopressin urine levels remained
      constantly elevated during the study period (mean +/- SD 13.5 +/- 7.8 day 1, 12.0
      +/- 9.9 day 3, 13.2 +/- 5.1 ng/l day 5, p = n.s.), while plasma hANP was
      significantly increased on the third day (626 +/- 495 vs. 298 +/- 240 pg/ml on
      day 1, p < .05). Urine sodium concentration, urine osmolality and osmolality and
      osmolar clearance were elevated significantly as well on day 3, p < .05, and
      correlated to hANP levels. Body weight decreased during the study by 8.2% on the
      third day and by 11.3% of birthweight on the fifth day. A significant increase in
      creatinine clearance occurred after the third day (p < .01), while free water
      clearance remained essentially the same during the first five days of life. We
      speculate that an increase in plasma hANP concentration on day 3 of life results
      in a natriuresis and osmolar diuresis without correlations or temporal
      relationships to hypervasopressinemia of the premature neonate with RDS.

PMID- 8537862
TI  - Phototherapy units in Brazil: are they effective?
AB  - The irradiance delivered by a phototherapy unit is an important contributing
      factor to its efficacy. However, measurement of irradiance during phototherapy
      requires the use of a photometer which is rarely available in the nurseries of
      developing countries. We assessed the irradiance of phototherapy units both in
      the laboratory and in all public hospitals of the City of Rio de Janeiro and
      found that: a) there is no consensus among companies manufacturing phototherapy
      units as to the number of fluorescent lights to be used in an equipment since
      this number varied from 4 to 8, b) over 1/3 of the phototherapy units analysed
      had 1 or more burnt out lamps, c) the mean irradiance delivered by phototherapy
      units was 2.36 +/- 0.75 muw/cm2/nm (0.6 to 4.4 muw/cm2/nm) which is considerably
      lower than the dose currently recommended for clinical efficacy. These results
      may be relevant to other developing countries where phototherapy meters are
      seldomly available and irradiance is not routinely measured.

PMID- 8537863
TI  - Endothelin 1-21 plasma levels in fetuses at 18-24 weeks of gestation.
AB  - This study aimed to establish normal endothelin (ET) ranges in non malformed
      appropriate for gestational age fetuses of 18-24 weeks gestation and to
      investigate a possible correlation between maternal and fetal ET plasma levels.
      Twenty "mother-fetus" pairs were included in the study. The determination of ET 1
      21 was performed by radioimmunoassay using 1 ml of fetal blood obtained by
      cordocentesis--indicated for various reasons--and in 2 ml of maternal venous
      blood. The statistical analysis involved the Wilcoxon test for pair differences
      and the Spearman rank correlation coefficient. Fetal and maternal ET 1-21 levels
      were respectively 11.39 +/- 2.22 pmol/L and 6.44 +/- 1.00 pmol/L. Fetal levels
      were significantly higher (p < 0.01) thus excluding passive ET transfer through
      the placenta, while no correlation between maternal and fetal levels was found.
      It is speculated that high fetal ET 1-21 levels result from increased ET
      production, which possess cell proliferative properties and/or decreased ET
      removal from the fetal circulation because of hypofunctioning lungs and kidneys.
      It can be assumed that the increased amounts of fetal ETs contribute to normal
      growth and development directly as well as by regulating vascular tonus and local
      blood flow.

PMID- 8537864
TI  - Subgingival distribution of Treponema denticola, Treponema socranskii, and
      pathogen-related oral spirochetes: prevalence and relationship to periodontal
      status of sampled sites.
AB  - Aims of this study were to comprehensively describe the intraoral distribution of
      the spirochete morphogroup and of 7 antigenically distinct oral treponema, and to
      relate their presence to periodontal status. Periodontal tissues were evaluated
      at 4 sites on every tooth except third molars and 76 subjects were classified
      according to the worst periodontal condition at any one site: Group 1, gingivitis
      (n = 13); Group 2, early periodontitis (n = 38); and Group 3, advanced
      periodontitis (n = 25). Subgingival plaque was collected from each half of every
      tooth evaluated clinically. Spirochetes were identified with phase contrast
      microscopy and specific treponema were detected immunochemically using monoclonal
      antibodies to Treponema denticola serovars A-D, T. socranskii subspecies bucalle,
      T. socranskii subspecies socranskii, and T. pallidum (pathogen-related oral
      spirochetes, PROS). The counting protocol was conservative and probably
      underestimated the actual presence of organisms. Spirochetes were found at one or
      more sites in approximately 60% of subjects in all groups. PROS were found in
      approximately 40% of subjects in all groups while T. denticola (predominantly
      serotype B) and T. socranskii (exclusively T. socranskii subsp. buccale) were
      more frequently observed in Group 2 (roughly 25% for both treponema) than in
      Groups 1 or 3. Overall, spirochetes were detected in less than 15% of the 4,040
      sites examined. Spirochetes were found at more sites of periodontitis (group mean
      range 20 to 40%) than of gingivitis (6 to 20%), and were only infrequently found
      at sites of periodontal health (4 to 10%). Spirochetes were identified most often
      in plaque from around molars and they were usually found in only one of two
      samples from individual teeth. Results of this study suggest that although
      spirochetes are most often found associated with periodontitis, their
      distribution is restricted and most periodontitis sites do not harbor
      spirochetes.

PMID- 8537865
TI  - Evaluation of a collagen membrane with and without bone grafts in treating
      periodontal intrabony defects.
AB  - The aim of this study was to compare the clinical regenerative capacity of
      collagen membrane with and without demineralized freeze-dried bone allografts
      (DFDBA) in treating periodontal intrabony defects. Ten systemically healthy
      patients with similar bilateral periodontal defects were scheduled for surgery.
      Each patient had at least > or = 6 mm clinical probing depth and loss of
      attachment at selected sites. Baseline measurements included gingival index (GI),
      plaque index (PI), gingival recession (GR), clinical attachment level (CAL),
      probing depth (PD), and mobility. At the time of surgery, the defects were
      randomly assigned to either test (collagen membrane plus DFDBA) or control group
      (collagen membrane only). Stent to base of the defects, stent to crest bone,
      crest of bone to base of the defect, and width of the defects were recorded at
      the time of surgery and reentry. Eight patients returned after 6 months for
      reentry surgery. Statistical analysis with a paired t test was used to evaluate
      the treatment effect and comparison between test and control groups. In addition,
      a McNemar test was used to analyze the significance of GI, PI, and mobility at
      different times. The result of this study indicated that both the collagen plus
      DFDBA and the collagen alone treatment groups had a significant decrease of PD
      (3.4 +/- 0.4 and 3.2 +/- 0.4 mm), gain of CAL (2.3 +/- 0.5 and 2.0 +/- 0.4 mm),
      and defect fill (1.7 +/- 0.3 and 1.9 +/- 0.9 mm) (P < 0.05) when compared to the
      presurgery status. However, there was no significant difference in PD, AL, GR,
      defect fill, crestal bone resorption, GI, PI, or mobility between the test group
      and control group. No adverse tissue reaction, infection, or delayed wound
      healing was noted throughout the treatment in either group. This study suggests
      that the collagen membrane is well tolerated by the human tissues. Both
      treatments, either collagen membrane plus DFDBA or collagen membrane alone,
      promoted significant resolution of periodontal intrabony defects. The addition of
      a bone graft (DFDBA) with a collagen membrane appears to add no extra benefit to
      the collagen membrane treatment.

PMID- 8537866
TI  - An assessment of the validity of a constant force electronic probe in measuring
      probing depths.
AB  - Reproducible and accurate measurement of probing depth and attachment levels is
      important in longitudinal studies and clinical monitoring of patients. The aim of
      this study was to determine the validity of a constant force electronic probe in
      comparison with a conventional probe in measuring probing depth. Thirty-three
      teeth scheduled for extraction from 15 patients were used in the study. Probing
      depths were measured with a constant force electronic probe and a conventional
      probe at six sites per tooth prior to extraction. The teeth were extracted,
      washed, and stained and the actual probing depth measured in the laboratory. The
      constant force electronic probe showed a consistent systematic bias to under
      measure pocket depths. The mean difference was 0.48 mm, which was statistically
      significant (P < 0.01). The conventional probe over measured by a statistically
      non-significant mean of 0.08 mm (P > 0.05). The measurements with the constant
      force electronic probe were not affected by the site or the position of the tooth
      in the mouth. The study demonstrated that the constant force electronic probe
      under measured the probing depths as determined in the laboratory and was less
      valid than the conventional probe. However, the validity of probing depth
      measurements using the constant force electronic probe was clinically acceptable.

PMID- 8537867
TI  - Levels of interleukin-1 beta and interleukin-8 in gingival crevicular fluids in
      adult periodontitis.
AB  - Recent in vitro findings indicate that cytokines represent an important pathway
      of connective tissue destruction in human periodontitis. The biological effects
      of interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) are relevant in this
      regard, and the objective of this study was to compare the levels of these
      molecules in gingival crevicular fluids (GCF) from patients with adult
      periodontitis (experimental group) and from individuals with clinically healthy
      gingiva (control group). GCF was collected for 30 seconds using a periopaper
      strip and the volume of the sample determined. Following elution of the fluid,
      assays for IL-1 beta and IL-8 were carried out by ELISA. The concentrations
      (ng/ml) of cytokines were calculated in the original volume of GCF on each strip.
      The total amounts (pg/site) of cytokines were expressed as the concentrations
      multiplied by volumes of GCF: The total amounts of IL-1 beta and IL-8 of the
      experimental group were significantly higher than the control group. The total
      amounts of both cytokines were markedly reduced following phase 1 periodontal
      treatment. The clinical parameters were positively related to the total amounts
      of IL-1 beta and IL-8. IL-1 beta concentrations and total amounts were also
      positively related to IL-8 suggesting that the GCF IL-8 levels are influenced by
      local IL-1 beta activities. These data indicate that the total amounts of IL-1
      beta and IL-8 exhibited dynamic changes upon severity of periodontal disease. The
      levels of IL-1 beta and IL-8 in GCF are valuable in detecting the inflammation of
      periodontal tissue.

PMID- 8537868
TI  - Platelet association with gingival tissue inflammation.
AB  - Platelets (PL) may be involved in the inflammatory process through the release of
      a variety of factors which could contribute to gingival tissue injury. Thus,
      conditions which result in the localized discharge of PL constitutents could lead
      to amplification of the inflammatory process at these sites. The purpose of this
      study was to determine if there was evidence of PL activation in gingival
      crevicular fluid and whether the degree of gingival inflammation, as measured by
      the gingival index (GI), was associated with the degree of platelet activation.
      This was monitored by assaying for beta-thromboglobulin (beta-TG), a platelet
      specific protein released from alpha granules of PL when activated. One uL
      samples of the fluids were obtained from human subjects from gingival sites with
      various GI scores. Fluid samples were also obtained at probe-induced bleeding
      gingival crevicular sites. beta-TG levels in the various fluids obtained from the
      crevice were determined by radioimmunoassay (RIA). The RIA data indicated that
      detectable beta-TG levels were observed in all samples, the means ranging from
      5.5 ng/ml to 45.2 ng/ml. Additionally, a positive association between the GI
      scores of 0 and 1 and the beta-TG levels where observed. For GI scores of 2 and
      above the beta-TG concentrations appeared to approach a maximum value. These
      findings provide evidence for PL activation and suggest a relationship with
      gingival inflammation.

PMID- 8537869
TI  - Bacterial colonization of the external and internal sulci and of cellulose
      membranes at time of retrieval.
AB  - Membrane exposure with bacterial contamination is often considered one of the
      main reasons for the lack of predictability in achieving complete regeneration of
      periodontal defects. Ten cellulose membranes, retrieved from 7 patients treated
      for Class II furcation lesions in lower molars with at least 4 mm of exposure at
      time of retrieval were studied. Contamination of exposed membranes was studied
      using SEM analysis of four surfaces of the membrane, upper external, lower
      external, upper internal, and lower internal surfaces. DNA probe analysis of
      three periodontopathic bacteria, Porphyromonas gingivalis, Prevotella intermedia,
      and Actinobacillus actinmycetemcomitans, was carried out for specimens collected
      from the external and internal sulci. The results suggest that bacterial
      contamination of the membranes could be controlled if proper pre- and
      postoperative care is followed, since significant amounts of any of the three
      periodontopathogenic bacteria studied were not found. The SEM analysis
      corroborated the DNA probe analysis since the predominant morphotypes detected
      were not suggestive of periodontopathogenic bacteria. The importance of membrane
      contamination and of root concavities in the lack of predictability of the GTR
      procedure is discussed.

PMID- 8537871
TI  - A newly-developed electrodeposited diamond scaler with high abrasive resistance.
AB  - A diamond scaler on which blade diamond particles were coated by
      electrodeposition was developed to improve the abrasive resistance of scaler
      blades. The electrodeposited coating was tested with diamond particles of four
      different sizes, designated D-4000 with 2 to 4 microns diameter of the particles;
      D-800 with 12 to 25 microns; D-600 with 20 to 30 microns; and D-400 with 30 to 40
      microns. The abrasive resistance of the scalers was examined quantitatively using
      a recently-developed automatic scaling apparatus that simulated the scaling
      process of hand instrumentation, as well as SEM observation of the blades. A
      series of abrasion tests suggested that all the diamond scalers except D-4000
      showed better abrasive resistance than the control (D-0), and that D-600 showed
      the highest abrasive resistance and cutting quality. The SEM observation also
      suggested that D-600 and D-400 might have higher abrasive resistance.
      Furthermore, the profilometric evaluation of the surface roughness of the scaled
      natural dentin after hand instrumentation indicated that the average surface
      roughness increased in the order of D-4000, D-800, D-600, and D-400, although no
      marked differences were observed among D-4000, D-800, D-600 and D-0, but not D
      400. These results suggested that the electrodeposited diamond scaler with 20 to
      30 microns diamond particles (D-600) might have marked abrasive resistance as
      well as cutting quality without remarkable damage to the tooth surface after
      conventional scaling procedure.

PMID- 8537870
TI  - Whole mouth microbiota effects following subgingival delivery of sanguinarium.
AB  - An increased incidence of antibiotic-resistant bacteria and yeast overgrowth has
      been reported following various periodontal treatments. The objective of this
      study was to detect possible overgrowth of opportunistic bacteria and fungi as
      well as changes in normal microbiota after application of a biodegradable
      delivery system containing 5% sanguinarium (ABDS-S) to one quadrant in a split
      mouth study. An oral hygiene quadrant served as a control. The ABDS-S treated and
      control periodontal sites as well as the saliva of 17 subjects were sampled prior
      to treatment, immediately after ABDS-S removal at 7 days, and again at 30 and 60
      days. At Day 7 sanguinarium-resistant bacteria increased in both control and ABDS
      S periodontal sites as well as in the saliva. Enteric Gram-negative bacilli in
      both control and ABDS-S periodontal sites were 2.2 to 3.4 log colony forming
      units higher at Day 7 compared to baseline. This overgrowth was transient in that
      levels became undetectable at Days 30 and 60. No such overgrowth was observed for
      C. albicans or other fungi, or for S. aureus or other staphylococci in any
      periodontal sites. Levels of Actinomyces increased at Days 30 and 60 in both
      control and ABDS-S sites as well as saliva. These changes strongly suggest that a
      7 day ABDS-S treatment in one quadrant of the mouth led to significant microbiota
      changes in the treated and control quadrants as well as in the saliva. Future
      microbial studies involving antimicrobials delivered by local delivery systems
      must consider the crossover effects of treatment inherent in the split-mouth
      design.

PMID- 8537872
TI  - The effect of ultrasonic irrigation before and after citric acid treatment on
      collagen fibril exposure: an in vitro SEM study.
AB  - The surface characteristics of periodontally diseased human teeth after two
      treatments were compared both before and after partial demineralization with
      citric acid. Thirteen teeth were obtained from patients with advanced periodontal
      disease. Three teeth were selected for control groups and 10 were used for
      experimental groups. All diseased root surfaces were identified and outlined. The
      roots were cut longitudinally into two sections. They were then scaled and root
      planed and the paired sections were separately classified into two control or two
      experimental groups. Three sections in control group 1 were rinsed by syringe
      with saline solution. The three sections in control group 2 were treated with
      ultrasonic irrigation. The 10 sections in experimental group 1 were rinsed by
      syringe with saline solution before and after citric acid application; the 10
      sections in experimental group 2 were irrigated ultrasonically before and after
      citric acid application. The concentration of the citric acid was 25% (pH 1.62)
      and the immersion time was 3 minutes. The root samples were examined by scanning
      electron microscope. A significant amount of grinding debris covered on all the
      root surfaces in control group 1, whereas smear was removed in control group 2.
      The features of root surfaces of the two experimental groups differed
      considerably. All specimens in experimental group 2 exhibited collagen fibrils
      exposed as a consequence of citric acid etching. On the other hand, the smear
      layer was not thoroughly removed from the root surface in experimental group 1,
      which meant that few collagen fibrils were exposed after partial
      demineralization. From these results, ultrasonic irrigation before and after
      citric acid application improves exposure of collagen fibrils, which may be
      desirable for clinical success in periodontal regenerative therapy.

PMID- 8537873
TI  - A case of myiasis gingiva.
AB  - A case of myiasis gingiva was diagnosed in an investigation designed to evaluate
      the histopathological features of the adjacent tissues of 100 advanced
      periodontal lesions. The patient was a 36-year old female and her chief complaint
      was discomfort and swelling in the area between the upper left central and
      lateral incisors. The patient's medical history, review of the symptoms, and
      family history were non-contributory and her oral hygiene was acceptable. The
      surgeon was not aware of anything unusual during the operation. Although the
      Parasitology Department was unable to define the entomologic identification of
      the infesting parasite from histopathological tissue slides, it was agreed that
      this case of myiasis might be produced by larvae of genus Sarcophaga or
      Enterobius vermicularis.

PMID- 8537874
TI  - Metastatic lung carcinoma involving the periodontium. Report of a case.
AB  - A case of metastatic bronchogenic carcinoma to the gingiva in a 47-year-old male
      is reported. The gingival lesion developed as a quickly growing mass and appeared
      2 months after surgical excision and radiotherapy of the lung carcinoma were
      completed. The gingival tumor was histopathologically diagnosed as a poorly
      differentiated squamous carcinoma. Comparative cytologic studies showed
      similarities between the gingival metastasis and the previous lung cancer.

PMID- 8537875
TI  - Abscess formation around the apex of a maxillary root form implant: clinical and
      microscopical aspects. A case report.
AB  - This case report describes the occurrence of an abscess in the periapical area of
      a root form maxillary titanium implant, with a radiolucent appearance and
      purulent discharge. The removal of the infected periapical tissues was carried
      out but the clinical symptoms of infection persisted, an attempt at guided tissue
      regeneration with a freeze-dried dura mater membrane notwithstanding, and it was
      necessary to remove the implant. The microscopical examination showed that it was
      possible to observe nonviable bone tissue, with absence of bone cells and areas
      of bone resorption in the apical portion of the implant. These microscopical
      features were compatible with an acute localized suppurative osteomyelitis.

PMID- 8537876
TI  - The acidic ribosomal proteins of different yeast species. Phosphorylation by
      ribosome-associated protein kinases.
AB  - Two major ribosomal proteins of Mr 13 kDa and 38 kDa were identified as
      phosphorylation substrates for ribosome-bound protein kinases from different
      yeast species. The phosphorylation level was much higher in ribosomes from the
      cells collected at the exponential growth phase, than in those from the
      stationary phase. Isoelectrofocusing of the protein band of 13 kDa and subsequent
      silver staining allowed to identify from four in the case of Pichia stipitis up
      to ten in Saccharomyces cerevisiae. Saccharomycodes Ludwigii, Torulopsis utilis
      and Kloeckera apiculata individual peptides. In the most of the yeast species
      studies five phosphorylated peptides were observed. However, only one or two such
      phosphopeptides were detected in Pichia stipitis and Trichosporon cutaneum
      ribosomes, respectively. The same phosphoprotein forms were identified in the in
      vivo 32P-labelling experiments.

PMID- 8537877
TI  - Microbial transformation of isoprenoid systems by means of fungi of Zoophthora
      genus--microbial transformation of compounds with alpha-campholenic system by
      means of fungus Zoophthora (Neopandora) sp.
AB  - Unsaturated ketones (4 and 10) and epoxides (2-3 and 8-9) were the main products
      of biotransformation performed by means of Zoophthora (Neopandora) phyllobii.
      Enantiospecificity of both reactions leading to these compounds strongly depends
      on the distance of reacting fragment of molecule from the chiral center at C-1'.

PMID- 8537878
TI  - Dielectric relaxation spectroscopy and some applications in the pharmaceutical
      sciences.
AB  - With a few exceptions, dielectric relaxation spectroscopy (DRS) has been largely
      neglected by pharmaceutical scientists, despite the potential for this technique
      as a noninvasive and rapid method for the structural characterization and quality
      control of pharmaceutical materials. DRS determines both the magnitude and time
      dependency of electrical polarization (i.e. the separation of localized charge
      distributions) by either measuring the ability of the material to pass
      alternating current (frequency domain DRS) or by investigating the current that
      flows on application of a step voltage (time domain DRS). DRS is thus (i)
      sensitive to molecular mobility and structure, (ii) non-invasive, and (iii)
      employs only mild stresses (a weak electromagnetic field) in order to measure the
      sample properties. The technique covers a broad-band frequency window (from 10(
      5) to 10(11) Hz) and therefore enables the investigation of a diverse range of
      processes, from slow and hindered macromolecular vibrations and restricted charge
      transfer processes (such as proton conductivity in nearly dry systems) to the
      relatively fast reorientations of small molecules or side chain groups. The
      dielectric response provides information on (i) structural characteristics of
      polymers, gels, proteins, and emulsions, (ii) the interfacial properties of
      molecular films, (iii) membrane properties, (iv) water content and states of
      water (and the effects of water as a plasticizer), and (v) lyophilization of
      biomolecules. This review article details the basis of dielectric theory and the
      principles of measuring dielectric properties (including a comprehensive account
      of measurement artifacts), and gives some applications of DRS to the
      pharmaceutical sciences.

PMID- 8537879
TI  - Racemization of ketorolac in aqueous solution.
AB  - The racemization of ketorolac was studied in aqueous buffered solution at 25 and
      80 degrees C and analyzed in detail with respect to the catalytic species in
      solution. The reaction has a U shaped pH rate profile at 80 degrees C with the pH
      of maximum stability occurring in the region of pH 3.0-7.5. A T90 value of 8
      months was observed for a 1.5% (R)-ketorolac tromethamine solution at pH 7.4 and
      25 degrees C. Additionally, the data shows that alternative salt forms are
      necessary in order to prepare a stable single isomer formulation. Alternative
      buffers, in particular phosphate buffer, provide formulations exhibiting a T90
      greater than 2 years.

PMID- 8537880
TI  - New synthetic amphiphilic polymers for steric protection of liposomes in vivo.
AB  - Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol),
      poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by
      derivatization with phosphatidyl ethanolamine via the terminal carboxy group and
      then incorporated into lecithin-cholesterol liposomes prepared by the detergent
      dialysis method. Following the biodistribution of liposomes in mice, all three
      polymers were shown to be effective steric protectors for liposomes and were able
      to sharply increase liposome circulation times in a concentration-dependent
      manner. The accumulation of liposomes in the liver decreases. The effects
      observed are similar to those found for liposomes modified with linear
      poly(ethylene glycol). At low polymer concentration, amphiphilic branched
      poly(ethylene glycol) seems to be the most effective liposome protector, most
      probably, because at the same molar content of anchoring groups, each attachment
      point carries two polymeric chains and doubles the quantity of liposome-grafted
      polymer comparing to linear poly(ethylene glycol).

PMID- 8537881
TI  - Determinants of placental drug transfer: studies in the isolated perfused human
      placenta.
AB  - There is little information on the effects of maternal and fetal placental blood
      flow rates, which can change independently, on the placental transfer rate of
      drugs of different placental permeabilities. We examined the effects of varying
      maternal and fetal perfusion flow rates on the placental transfer of three model
      compounds; antipyrine (high permeability), diclofenac (intermediate
      permeability), and cimetidine (low permeability) in the single-pass, dual
      perfused lobule of the isolated human placenta. In variable flow ratio
      experiments (n = 9) fetal perfusate flow rate was held constant while a different
      maternal flow rate was used in each of five 25-min phases such that the
      maternal/fetal flow ratio ranged from 0.16 to 3.3. In constant flow ratio
      experiments (n = 4), the flow ratio was kept at 2.0, while maternal and fetal
      flow rates were varied from 4-18 and 2-9 mL/min, respectively. In the variable
      flow ratio experiments, the fetal transfer fraction (fetal venous/maternal
      arterial drug concentrations) varied approximately fivefold among the five phases
      for each of the three drugs. Therefore, placental transfer was flow dependent
      regardless of placental drug permeability. By contrast, in the constant flow
      ratio experiments, fetal transfer fraction was unchanged throughout the five
      phases for each of the three drugs. Of the various kinetic models that have been
      formulated to account for the different possible vessel geometries, the double
      pool flow model, which is a venous equilibrium model and predicts the least
      efficient drug transfer rate of those proposed, together with a small maternal
      arteriovenous shunt, produced the best fit overall.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8537882
TI  - Transdermal delivery of dideoxynucleoside-type anti-HIV drugs. 1. Stability
      studies for hairless rat skin permeation.
AB  - The stability of dideoxynucleoside-type anti-HIV drugs in solution when in
      contact with hairless rat skin was investigated in order to study the feasibility
      of their transdermal delivery. The freshly excised dorsal region of hairless rat
      skin was mounted on Valia-Chien skin permeation cells, and both epidermis (donor)
      and dermis (receptor) were extracted with isotonic phosphate buffer (pH 7.4) at
      37 degrees C for 24 h. Zalcitabine (DDC), didanosine (DDI), and zidovudine (AZT)
      were found to be stable in the extract of the epidermis at 37 degrees C for at
      least 30 h. However, DDC and DDI degraded in the extract of the dermis following
      first-order kinetics at both 25 and 37 degrees C, while AZT was stable at 37
      degrees C for at least 30 h. The degradation mechanism(s) of DDC and DDI was
      (were) studied by analyzing HPLC chromatograms and by evaluating the drug
      stability in the extract which was filtered to remove any microbes. An
      unidentified peak produced by DDC in the dermis extract did not appear when the
      drug was added to the filtered extract, which suggested a bacterial degradation
      of DDC. On the other hand, DDI was unstable even in the filtered extract and
      produced a degradation product which corresponded to hypoxanthine, which
      suggested that a cutaneous enzyme is also involved in the degradation of DDI. DDC
      was stabilized by the addition of 0.01% (w/v) of an antibacterial agent, such as
      thimerosal or gentamicin, in the receptor solution, while DDI was stabilized by
      0.01% (w/v) purine nucleoside phosphorylase inhibitor, i.e., p
      chloromercuribenzoic acid. These results show the importance of stability studies
      when designing skin permeation experiments using hairless rat since compounds
      with similar chemical structures can have different stability profiles when in
      contact with hairless rat skin.

PMID- 8537883
TI  - Development of an ultracentrifuge technique to determine the adhesion and
      friction properties between particles and surfaces.
AB  - The extension of a centrifuge technique to measure adhesion and friction forces
      to an ultracentrifuge has been described. The equipment and procedure provide
      many experimental possibilities of which the adhesion of single particles to flat
      compacted powder surfaces has been used to measure the adhesion and friction
      force of starch microspheres to microcrystalline cellulose. The equipment used
      allows the positioning of the adhesion samples in the rotor in such a way that
      any angle between the centrifugal force vector and the flat sample surface can be
      obtained, and hence both adhesion and friction forces can be measured. The
      adhesion strength between starch microspheres and microcrystalline cellulose
      could initially be increased by applying a higher press-on force. However, a
      maximum plastic deformation and hence maximum contact area between the spheres
      and the surfaces was eventually reached, and any further application of press-on
      force appeared to lead only to more elastic deformation and hence not to an
      increase in adhesion strength. The friction between the starch microspheres and
      the compacted microcrystalline cellulose surfaces at a maximum deformation of the
      spheres is still very low, so that starch microspheres could be used as excipient
      in mixtures including microcrystalline cellulose for example in tabletting.

PMID- 8537884
TI  - Water mobility in poly(ethylene glycol)-, poly(vinylpyrrolidone)-, and gelatin
      water systems, as indicated by dielectric relaxation time, spin-lattice
      relaxation time, and water activity.
AB  - The mobility of water molecules present in poly(ethylene glycol) (PEG)-,
      poly(vinylpyrrolidone) (PVP)-, and gelatin-water systems was determined by
      dielectric relaxation and 17O NMR spectroscopy. Water activity was also measured.
      Dielectric relaxation spectra indicate that all the polymer systems studied
      contained water exhibiting a dispersion at a frequency > 10(9) Hz; in other
      words, water with high mobility close to that of bulk water. The dielectric
      relaxation time of the highly mobile water increased as polymer concentration
      increased. The PVP- and gelatin-water systems also contained water exhibiting a
      dispersion at a frequency < 10(9) Hz, which can be considered to be "bound water"
      with a restricted mobility because of its association with polymer molecules.
      Dielectric relaxation spectroscopy was used to determine water mobility
      separately for the populations of highly mobile water and bound water, whereas
      NMR relaxation spectroscopy was used to determine the average mobility of both
      populations. The spin-lattice relaxation time of water in these polymer-water
      systems showed a deviation from the isotropic two-state model. Dielectric
      relaxation data indicate that this deviation can be ascribed to variations in the
      relaxation time of highly mobile water caused by a change in polymer
      concentration. The dielectric relaxation time of highly mobile water in the
      gelatin system did not change with a change in polymer concentration to the
      extent that it did in the PEG and PVP systems. This result is consistent with a
      slight change in water activity of the gelatin system with increasing polymer
      concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537885
TI  - Liposomal entrapment of suramin(II): interaction of suramin with phospholipids of
      various chain lengths.
AB  - Previously, we reported that the entrapment of suramin in
      dipalmitoylphosphatidylcholine (DPPC, C16) multilamellar liposomes ranged from
      25% to 65% and the addition of 30-50 mol% cholesterol (CHL) greatly reduced
      entrapment. Entrapment of small molecules similar to suramin, disodium 1,5
      naphthalenedisulfonic acid (5.5%) and sodium 3-amino-2,7-naphthalenedisulfonic
      acid (1.2%), were very low. In the present study, the entrapment and interaction
      of suramin with dilauroylphosphatidylcholine (DLPC, C12),
      dimyristoylphosphatidylcholine (DMPC, C14), and distearoylphosphatidylcholine
      (DSPC, C18) liposomes was investigated. DLPC and DMPC showed 2-3-fold higher
      entrapment percentages (95.1% and 74.2%, respectively) than DPPC (37%). However,
      the entrapment with DSPC (29%) was about 25% lower than DPPC. Adding 50 mol%
      cholesterol greatly reduced suramin entrapment for all phospholipids. The
      entrapment of polysulfonated dyes such as Evans blue, Direct blue 1, or Trypan
      blue, which are structurally similar to suramin, was found to be in the same
      order of DLPC > DMPC > DPPC > DSPC. Differential scanning calorimetry of aqueous
      dispersions of DLPC and DMPC with suramin showed more apparent interaction than
      for DPPC and DSPC. These results suggest that a large portion of the associated
      suramin and other polysulfonated compounds results from binding to the surface of
      the phospholipid bilayer or intercalation into the liposomal bilayer. The
      phospholipid chain length effect on entrapment may be due to the lower net van
      der Waals interaction between hydrocarbon chains for shorter acyl chains which
      also increases the bilayer intermolecular spacing. Such effects could then
      increase the ability of suramin to interact with individual phospholipid
      molecules.

PMID- 8537886
TI  - A new pH-metric methodology for the determination of thermodynamic inclusion
      constants of guest/cyclodextrin complexes.
AB  - A new methodology of pH-metric data treatment was developed to extract the
      stoichiometry and the thermodynamic association constants of guest-cyclodextrin
      inclusion complexes in dilute aqueous solution when the guest is a participant in
      an acid-base equilibrium. pH-metric titration curves in the presence of
      cyclodextrin (CD) were treated by a curve-fitting technique according to a
      nonlinear least-squares regression. Equations corresponding to the different
      kinds of acid-base pairs (AH/A-, BH+/B) and stoichiometries (1:1 and 1:2) were
      established. The methodology was validated by studying the 5-phenylbarbituric
      acid complexation with beta-CD and the 4-cyanobenzoic acid complexation with
      alpha-CD. Then it was applied to chlorpromazine. Both the acid form (constant K1
      = 3260) and the base form (constant G1 = 13,100) gave complexes with beta-CD
      according to 1:1 stoichiometry.

PMID- 8537887
TI  - Preformulation studies of a novel HIV protease inhibitor, AG1343.
AB  - AG1343 is a novel human immunodeficiency virus (HIV) protease inhibitor designed
      using protein structure-based techniques and intended for chronic oral
      administration in the treatment of AIDS-related conditions. The compound is the
      mesylate salt of a basic amine with a molecular weight of 663.90, pKa of 6.0, and
      partition coefficient (log P) of 4.1. Examination of the physicochemical
      properties of a bench-scale lot of the bulk drug was undertaken in order to
      establish a preformulation database and to begin development of an oral
      formulation suitable for phase I clinical trials. A stability-indicating gradient
      HPLC method was developed, and initial stability studies indicated that the
      compound is relatively stable under accelerated conditions. Water solubility and
      intrinsic dissolution rate studies, however, revealed the potential for
      dissolution rate-limited absorption. Alternative salts were prepared and
      evaluated for water solubility relative to the mesylate. A pH-solubility profile
      for AG1343 was generated and its solubility in various pharmaceutical solvents
      was determined. Formulation into several prototypical oral dosage forms for in
      vitro evaluation in animal models prior to phase I clinical trials resulted in a
      several-fold difference in bioavailability between these formulations.

PMID- 8537888
TI  - Distribution of free and liposomal annamycin within human plasma is regulated by
      plasma triglyceride concentrations but not by lipid transfer protein.
AB  - Annamycin (Ann) is a lipophilic and non-cross-resistant anthracycline antibiotic
      currently in clinical development as a liposomal formulation (L-Ann) composed of
      dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG).
      Previous studies have demonstrated that the incorporation of Ann into these
      liposomes prolongs its terminal serum half-life and increases the tumor levels of
      the drug. However, an explanation for the altered pharmacokinetics and
      pharmacodynamics of doxorubicin and Ann when entrapped into these multilamellar
      lipid vesicles remains unknown. Since the distribution of lipophilic compounds
      within plasma lipoproteins has been shown to influence the pharmacokinetics and
      organ distribution of a number of lipophilic compounds and this distribution
      appears to be regulated by lipid transfer protein (LTP), we studied the
      distribution of Ann and L-Ann among plasma lipoproteins and the influence of LTP
      on the distribution of Ann and L-Ann among plasma lipoproteins. Our results
      concluded that when Ann was incorporated into liposomes composed of DMPC and
      DMPG, over 65% of the initial Ann concentration would distribute into the high
      density lipoprotein (HDL) fraction and that free Ann and L-Ann distribution
      within human plasma was independent of LTP activity. In addition, we observed
      that the increase in total plasma triglyceride (TG) concentrations (through the
      increase of very low-density lipoproteins (VLDL)) resulted in the increase
      distribution of Ann and L-Ann within the TG-rich VLDL fraction. However,
      increasing the VLDL core TG/cholesterol ratio decreased Ann distribution into
      VLDL. These findings suggest that initial Ann distribution is regulated by a
      mechanism that does not involve LTP, but through its interaction with plasma VLDL
      TG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537889
TI  - Duration of opioid antagonism by nalmefene and naloxone in the dog: an integrated
      pharmacokinetic/pharmacodynamic comparison.
AB  - A continuous fentanyl infusion was administered to eight adult, male beagle dogs
      for a duration of approximately 400 min at a rate of 30 micrograms/kg/h. The
      extent of respiratory depression was quantified by continuous, noninvasive,
      transcutaneous pCO2 recordings. Upon reaching a pseudosteady-state of respiratory
      depression at approximately 120 min of fentanyl infusion, the animals then
      received, in a 2 x 2 crossover fashion separated by approximately 3 weeks, 30
      minute equiefficacious infusions of nalmefene (12 micrograms/kg/h) or naloxone
      (48 micrograms/kg/h). Multiple venous blood samples were taken throughout the
      dosing regimen, and the resulting fentanyl, nalmefene, or naloxone plasma
      concentrations were determined. The concentration-time data were analyzed by
      noncompartmental methods and subsequently linked to the pharmacodynamic effect
      data by a competitive antagonism link model. Separately, the biophase
      concentrations were linked to the plasma concentration-time profiles through a
      single-exponential conduction function. The various
      pharmacokinetic/pharmacodynamic parameters resulting from this semiparametric
      analysis were analyzed by ANOVA, using a statistical model that considers
      carryover effects. The results of these analyses indicate that several
      pharmacokinetic/pharmacodynamic parameters of the two antagonists were
      comparable. However, nalmefene had a significantly more protracted terminal
      disposition and a significantly greater persistency in the biophase evaluated
      over the experimental time frame from 0 to 450 min.

PMID- 8537890
TI  - Water/n-octanol partition coefficients of 1,2-dithiole-3-thiones.
AB  - Water/n-octanol partition coefficients (log P) for 33 1,2-dithiole-3-thiones and
      for 18 1,2-dithiol-3-ones were determined by RP-HPLC measurement of the
      concentration of the solute in aqueous solution after equilibrium. Depending on
      the nature of the substituents (alkyl or aryl) and their position(s) (4,5, or
      both) on the dithiole nucleus, some peculiar behaviors were revealed. Therefore,
      different fragmental constants containing the 1,2-dithiole-3-thione nucleus were
      inferred in order to calculate in a complementary work, a priori, the log P
      values of new dithiolethiones and dithiolones.

PMID- 8537891
TI  - Chemical hydrolysis of phospholipids.
AB  - Hydrolysis kinetics of phospholipids in liposomes composed of
      dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine/cholesterol
      (DPPC/CHOL) 10/4 (molar ratio) and egg phosphatidylcholine (EPC) at pH 4.0 and
      different temperatures could be described by Arrhenius curves without breaks.
      However, the Arrhenius curves for the hydrolysis of liposomal DPPC and
      distearoylphosphatidylcholine (DSPC) under the same conditions were biphasic. A
      break was observed in the curves extending over a broad range before and after
      the known Tm of each of these phospholipids in liposomes (42 and 56 degrees C,
      respectively). The activation energy (Ea) for the hydrolysis of liposomal DPPC
      and DSPC below the Tm was substantially larger than the Ea for liposomal DMPC,
      DPPC/CHOL 10/4, and EPC and decreased when DPPC was mixed with CHOL in a 10/4
      molar ratio. Hardly any influence of the presence of alpha-tocopherol,
      cryoprotectants (glucose, trehalose, sucrose, and propylene glycol), and the
      major hydrolysis products lysophospholipids and fatty acids or of the absence of
      sodium chloride on the hydrolysis kinetics of DPPC at pH 4.0 and 30 degrees C was
      observed. Changes in fatty acid chains and size did not influence the hydrolysis
      rate constant (kobs) of liposomal phospholipids at pH 4.0 and 30 degrees C
      either. The only effects of uncharged compounds on the kobs of liposomal DPPC at
      pH 4.0 and 30 degrees C were found upon mixing with a high concentration of the
      detergent Triton X-100 or palmitic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8537892
TI  - Drug-protein conjugates: haptenation of 1-methyl-10 alpha-methoxydihydrolysergol
      and 5-bromonicotinic acid to albumin for the production of epitope-specific
      monoclonal antibodies against nicergoline.
AB  - Two types of monoclonal antibodies were used for the determination of nicergoline
      in biological matrices. The antibodies were prepared with the hydrolysis products
      5-bromonicotinic acid and 1-methyl-10 alpha-methoxydihydrolysergol after
      hemisuccinoylation to haptens. The current amide bond-generating methods (mixed
      anhydride-, carbodiimide-, carbodiimide/sulfo-N-hydroxysuccinimide-, and
      dicyclohexylcarbodiimide/N-hydroxysuccinimide methods) were used in bovine serum
      albumin (BSA)-coupling techniques and yielded conjugates that were haptenated to
      varying extents. The conjugates exhibiting 23 mol of 1-methyl-10 alpha
      methoxydihydrolysergol (MMD) or 41 mol of 5-bromonicotinic acid (BNA) per mole of
      BSA were used for both immunization of mice and for coating the wells of the
      microtiter plates to select hybridomas and investigate specificity of the
      obtained antibodies. The results of hapten-inhibition ELISA using antigen-coated
      wells indicate that the supernatant of MMD-specific hybridoma exhibited 50%
      inhibition of antibody binding at 17 +/- 2 micrograms of MMD and at 24.5 +/- 2
      micrograms of nicergoline, and the BNA-specific hybridoma exhibited similar
      inhibition at 147 +/- 6 micrograms of BNA and 500 +/- 30 micrograms of
      nicergoline. A main requirement for analytical purposes is that two different
      types of monoclonal antibodies recognize two different epitopes on nicergoline
      and its main metabolite, as shown by hapten-inhibition ELISA.

PMID- 8537893
TI  - Solution- and solid-state structures of the (-)-n-heptylcarbamate of geneseroline
      and its hydrochloride salt.
AB  - The solid state structures of the (-)-n-heptylcarbamate of geneseroline and its
      hydrochloride salt were determined by single crystal X-ray diffraction analysis.
      Both compounds gave crystals belonging to the orthorombic P2(1)2(1)2(1) space
      group with a = 27.597(7) A, b = 8.899(2) A, c = 9.290(2) A, V = 2281.5(9) A3, Z =
      4, and R = 0.0682 for the base and a = 11.300(1) A, b = 8.3485(5) A, c =
      24.141(2) A, V = 2277.3(3) A3, Z = 4, and R = 0.0482 for the salt. X-ray and 1H
      NMR analysis revealed that the base is a 1,2-oxazine derivative. The six-membered
      ring adopts a 4C1 chair conformation in the solid-state, whereas, in CDCl3
      solution, it exists as a mixture of two possible chair conformers, 4C1 and 1C4,
      with the N-methyl group in the equatorial position (ratio approximately 75:25).
      The salt is an N-oxide derivative; the five-membered ring adopts different
      envelope conformations in the solid-state and in CDCl3 solution, suggesting a
      certain flexibility. In more polar solvents, the salt partially undergoes fast
      inversion at the tetrahedral nitrogen, giving rise to the corresponding epimer.

PMID- 8537895
TI  - Preparation and biodistribution studies of 111In-labeled acetylacetone-(2
      hydroxypropyl)-beta-cyclodextrin.

PMID- 8537894
TI  - Characterization of p-hydroxyphenobarbital glucuronide generated from immobilized
      rat hepatic UDP-glucuronosyltransferase.

PMID- 8537896
TI  - In-vitro release from corticosteroid ointments.

PMID- 8537897
TI  - Isolation and characterization of two major degradation products of dyclonine
      hydrochloride.
AB  - Dyclonine hydrochloride, a local anesthetic, is known to degrade in aqueous
      media. In this paper, the isolation and characterization of two major degradation
      products, formed by heating of an aqueous solution of dyclonine hydrochloride for
      2 weeks at 50 degrees C, are presented. The proton and carbon-13 nuclear magnetic
      resonance, infrared, and mass spectral data reported conclusively show the two
      products to be 1-(4-butoxyphenyl)-2-propen-1-one and 1-(4-butoxyphenyl)-3-hydroxy
      1-propanone. The proton and carbon-13 nuclear magnetic resonance spectral data of
      the free dyclonine base are also included.

PMID- 8537898
TI  - Permeation of steroids through human skin.
AB  - The permeabilities of many steroids through human skin have been previously
      measured and reported in the literature. Analysis of these data reveals that
      significant discrepancies exist between the measurements of Scheuplein et al. and
      those of other groups. Six of the 14 steroids which were examined by Scheuplein
      et al., aldosterone, corticosterone, estradiol, hydrocortisone, progesterone, and
      testosterone, have also been examined by other groups. For each of these
      steroids, the permeability measurements of Scheuplein et al. are lower than those
      reported by other groups by factors of between 5.0 and 77. Eight independent
      measurements of the permeability of estradiol are in good agreement with one
      another, but are greater than the value reported by Scheuplein et al. by factors
      of between 11 and 20. Several possible sources of experimental error, including
      the variability of the skin samples, the differences in the experimental
      temperature, the establishment of steady-state conditions, the use of
      radiolabeled drugs, and the skin preparation technique, have been considered and
      do not appear to account for the magnitude of the observed discrepancies nor for
      the fact that the data of Scheuplein et al. are consistently lower than those
      reported by other groups.

PMID- 8537899
TI  - Computer-assisted measurement in diabetic patients with and without foot
      ulceration.
AB  - Computer-assisted measurement of sensibility was done at four anatomical sites of
      the foot of patients with diabetes with (19) and without (40) foot ulceration.
      Cutaneous pressure threshold measurements of patients with diabetes were compared
      with measurements on 30 patients without diabetes who had nonulcerated feet. Both
      groups had mean one-point static and moving touch, and two-point discrimination
      thresholds significantly different from the general population. Computer-assisted
      sensibility testing demonstrated significantly higher pressure thresholds for one
      point static and moving touch and two-point discrimination in the ulcerated
      compared with the nonulcerated foot of patients with diabetes. This measurement
      technique is valid for documenting diminished sensation in the foot.

PMID- 8537901
TI  - Perioperative monitoring of potentially toxic drugs.
AB  - A list of drugs considered to have a narrow therapeutic margin are discussed.
      These potentially toxic drugs will be reviewed, including recommended therapeutic
      ranges, when therapeutic levels should be obtained, and additional laboratory
      studies that may be required for patients on these medications who are preparing
      to undergo surgery.

PMID- 8537900
TI  - Brachymetatarsia. Case report and surgical considerations.
AB  - The authors present a case of congenital idiopathic brachymetatarsia of the
      fourth metatarsal. A combination of techniques was used to address the components
      of the deformity and its correction, which include preoperative soft tissue
      stretching, Z-skin plasty, Z-tendon lengthening, Z-lengthening metatarsal
      osteotomy with internal screw fixation, and bone allografting. Conventional
      autograft harvesting complications and external fixation were avoided. This case
      demonstrates the correction of a brachymetatarsal using combined and modified
      techniques.

PMID- 8537902
TI  - Incurvated nail. Does the phalanx determine nail plate shape?
AB  - This study examines the relationship between the shape of the nail plate of the
      hallux and the base of its distal phalanx. Twenty-three cadaver specimens were
      examined anatomically for nine variables. These variables represented the
      following: height and width of the distal phalanx base; height and width of the
      proximal aspect of the nail plate; distal shape of the nail plate; ratio of the
      nail plate height and width and structural index of the nail plate. Statistics
      for the variables are presented using correlation coefficients between nail
      structural index and bone structural index. The study shows a high and
      significant correlation between the shape of the proximal aspect of the nail
      plate and that of the phalangeal base.

PMID- 8537903
TI  - Statistical analysis of 307,601 tumors and other lesions of the foot.
AB  - This laboratory study is limited to lesions submitted from office procedures and
      makes no claims or comparison regarding statistical data from hospitals, where
      most malignancies are excised. This study is ongoing, and will be updated
      regularly to observe trends and alert practitioners to changing patterns of
      incidence.

PMID- 8537904
TI  - Digital artery microembolization following coronary artery surgery.

PMID- 8537905
TI  - Aneurysmal bone cyst arising from a giant cell tumor of the calcaneus.

PMID- 8537906
TI  - Henoch-Schonlein purpura. Case report and review of the literature.
AB  - The similarity in the skin manifestations in Henoch-Schonlein purpura as compared
      with systemic lupus erythematosus and rheumatoid arthritis complicates diagnosis.
      Therefore, analysis of hematologic studies, tissue histology, and
      immunofluorescence should be thoroughly reviewed.

PMID- 8537907
TI  - Space-occupying lesions as a cause of tarsal tunnel syndrome.
AB  - In diagnosing the etiology of tarsal tunnel syndrome, the practitioner must be
      aware of space-occupying lesions as a possibility. These masses, rarely found
      beneath the laciniate ligament, can occur. Satisfying results have occurred after
      removal of these lesions. Careful dissection will assure preservation of the
      nerve and prevent sensory or motor loss.

PMID- 8537908
TI  - Blue nevus.
AB  - Dermal melanocytes are generally most numerous in the sacral, dorsal hand, and
      dorsal foot. There is also a slight rise that often occurs toward the axial line
      of the trunk. The practitioner needs to be aware and take necessary measures to
      properly diagnose the blue nevus from other forms of pigmented skin lesion. The
      authors believe that surgical excision with proper pathologic follow-up is the
      preferred treatment.

PMID- 8537909
TI  - Cimetidine therapy for plantar warts.
AB  - Although more than 50% of warts resolve spontaneously within 2 years, many, if
      untreated, have the propensity to spread and cause considerable discomfort. There
      are several treatments to date; however, most cause some type of tissue damage.
      Because spontaneous resolution of warts can occur, the role of cimetidine in the
      treatment of warts remains controversial. Anecdotal reports suggest cimetidine
      may have a role in the treatment of plantar warts with no side effects or tissue
      damage. A double blind trial in a large population should be conducted to further
      verify the effects of treating viral warts with cimetidine.

PMID- 8537911
TI  - p53 protein and Ki-67 reactivity in epithelial odontogenic lesions. An
      immunohistochemical study.
AB  - Forty-five examples of epithelial odontogenic lesions (9 ameloblastomas (AB): 13
      odontogenic keratocysts (OKC): 15 dentigerous cysts (DC): 6 radicular cysts (RC):
      and 2 odontogenic carcinomas (OC)) were immunohistochemically analyzed for the
      presence of p53 protein (p53P) and proliferative activity as indicated by
      positivity for Ki-67 antigen. p53P+ cells, detected as dense and/or faint nuclear
      staining, were found in 42 of the 45 odontogenic lesions examined. Dense p53P
      reactivity was most commonly detected in OKC, AB and OC, with other lesions
      generally exhibiting only weak nuclear reactivity. Numbers of Ki-67 positive
      cells as well as p53P+ cells were scored semiquantitatively. Although the
      presence/absence of densely stained p53P+ cells was broadly related to Ki-67+
      cell numbers, there were no differences in p53P+ cell numbers between lesions
      exhibiting differences in proliferative activity. These results suggest that
      overexpression of p53P, rather than increased numbers of p53P+ cells, is related
      to proliferation in odontogenic epithelial lesions.

PMID- 8537910
TI  - Immunohistochemical localization of fibroblast growth factor-1 (FGF-1) and FGF-2
      in cultured human ameloblastoma epithelial cells and ameloblastoma tissues.
AB  - Fibroblast growth factor-1 (FGF-1) and FGF-2 are mitogenic polypeptides that may
      contribute to neoplastic cell proliferation. In the present study, we established
      a serum-free culture system for ameloblastoma cells and demonstrated that the
      addition of FGF-1 and FGF-2 enhanced cell growth in a dose-dependent manner.
      Immunoperoxidase staining of cultured cells demonstrated strong expression of FGF
      1 and FGF-2. In tissue specimens, FGF-1 was localized in epithelial cell
      components of ameloblastomas, whereas FGF-2 was mainly found in the basement
      membranes with only moderate staining in epithelium. These data suggest that both
      FGF-1 and FGF-2 may contribute to the growth and development of ameloblastomas.

PMID- 8537912
TI  - A fluorescence in situ hybridization (FISH) analysis with centromere-specific DNA
      probes of chromosomes 3 and 17 in pleomorphic adenomas and adenoid cystic
      carcinomas.
AB  - Aberrations of chromosomes 3 and 17 were studied by FISH using centromere
      specific DNA probes in 11 salivary adenoid cystic carcinomas (ACC) and 8 salivary
      pleomorphic adenomas (PA), with 3 lymph nodes as controls. Two hybridized signals
      were detected in 92.8 +/- 2.7% of controls, 73.2 +/- 7.0% of PA and 66.8 +/- 7.9%
      of ACC cells for chromosome 3, and in 90.4 +/- 2.3% of controls, 59.5 +/- 25.0%
      of PA and 44.8 +/- 20.2% of ACC for chromosome 17. More than 3 hybridized
      signals, which indicate polysomy, were observed in 3.1% of controls, 15.5% of PA
      and 22.9% of ACC cells for chromosome 3, and in 1.2% of controls, 10.3% of PA and
      23.1% of ACC cells for chromosome 17. A single hybridized signal was much more
      frequent for chromosome 17 than for chromosome 3. These findings suggest that
      polysomy of both chromosomes occurs during the development of salivary gland
      tumors, and its frequency is increased in adenoid cystic carcinoma as compared to
      pleomorphic adenoma. In addition, monosomy of chromosome 17 could possibly be
      significant in salivary gland tumors.

PMID- 8537913
TI  - Clinical evaluation of different treatment methods for oral submucous fibrosis. A
      10-year experience with 150 cases.
AB  - Over a 10-year period (1982-1991); a total of 150 patients divided into two
      groups with varying degrees of oral submucous fibrosis (OSF) were treated by
      either medical or surgical therapies. Medical treatment involved (a) conservative
      oral administration of vitamin B-complex, buflomedial hydrochloride and topical
      triamcinolone acetonide 0.1%, or (b) conventional submucosal injections of a
      combination of dexamethasone and hyaluronidase, or (c) a combination of both (a)
      and (b). The surgical group was treated by the excision of fibrotic tissues and
      covering the defect with split-thickness skin, fresh human amnion, or buccal fat
      pad (BFP) grafts. Treatment was chosen according to the stage of clinical
      progression to gain maximal interincisal distance (ID). The cases were followed
      up by monthly examinations for at least two years, or when possible even longer.
      A combination of (a) and (b) medical treatment was satisfactory in cases of mild
      impairment (ID > 20 mm) but in the long term it led to symptomatic relief only.
      Surgical therapy, on the other hand, when accepted by the patients, led to a
      significant improvement of trismus in cases of severe limitation (ID < 20 mm).
      Following this strategy, an additional ID increase was observed in all patients.
      BFP grafting was particularly successful in diminishing scarring after two years
      as compared with the other two grafts. Together with a cessation of the betel
      quid chewing habit before and after therapy, these treatment regimens combined
      with daily mouth opening exercises were found to be necessary to manage OSF cases
      in early and advanced stages of progression.

PMID- 8537914
TI  - Increased lysyl oxidase activity in fibroblasts cultured from oral submucous
      fibrosis associated with betel nut chewing in Taiwan.
AB  - Growth characteristics and lysyl oxidase activity of fibroblasts derived from
      human normal mucosa (NM) and oral submucous fibrosis (OSF) associated with betel
      nut chewing were compared in cell cultures. The growth rates of cultured cells
      were identified by plating 5 x 10(5) cells/35 mm culture dish (Day 0) and every
      24 hours cell proliferation was determined by quantifying the cell number (using
      a hemocytometer). The third to seventh passages were used. A medium without serum
      but supplemented with 5 mg/ml bovine serum albumin was substituted for the
      original medium at the subconfluent period and cultured for an additional 24 h.
      The medium was collected and used for assays of protein content and lysyl oxidase
      activity. Lysyl oxidase activity was assayed with [4,5-3H]--lysine labelled
      purified chick--embryo aorta elastin substrate. After incubation for 10 h at 37
      degrees C, the enzyme activity was measured from 3HHO (tritiated water) separated
      by ultrafiltration using Amicon C-10 micro-concentrators. The results showed the
      mean doubling time of OSF fibroblasts was 3.2 days and of NM fibroblasts was 3.6
      days. NM fibroblasts became confluent at day 6 as determined by cell number,
      while OSF fibroblasts were confluent by Day 5. Furthermore, the immunoenzymatic
      assay for BrdUrd incorporation revealed that OSF fibroblasts proliferate
      significantly faster than NM fibroblasts under standard culture conditions. Both
      total protein content (10.84 +/- 1.15 mg/ml) and lysyl oxidase activity (3558.6
      +/- 345.5 cpm/10(6) cell) in OSF fibroblasts were greater than in NM fibroblasts
      (6.35 +/- 0.96 mg/ml and 2436.0 +/- 352.6 cpm/10(6) cell). The results of this
      study provide evidence that fibroblasts derived from oral submucous fibrosis
      (OSF) tissue and normal mucosa (NM), although similar in many respects, exhibit
      specific differences in proliferation rates and lysyl oxidase activity. Moreover,
      collagen deposition in OSF tissue may, at least in part, be ascribed to increased
      lysyl oxidase activity.

PMID- 8537915
TI  - High numbers of T cells in gingiva from patients with human immunodeficiency
      virus (HIV) infection.
AB  - A quantitative, immunohistologic evaluation of CD3+, CD4+ and CD8+ cells was
      carried out on gingival biopsies from 25 HIV-infected persons with gingivitis or
      periodontitis and 13 HIV-seronegative persons with periodontitis. CD3+ T cells
      were found in all biopsies. CD8+ cells were significantly more numerous and the
      CD4+/CD8+ ratio was significantly decreased in the gingival connective tissue of
      the HIV+ patients (p < 0.05). The number of CD4+ lymphocytes subjacent to the
      pocket epithelium was moderately lower in the HIV+ patients as compared to the
      HIV patients (p < 0.05). HIV+ patients with a history of necrotizing periodontal
      disease had fewer CD4+ cells subjacent to the oral gingival epithelium than
      patients without such disease (p < 0.05). The general HIV-related changes in T
      lymphocyte numbers were therefore reflected in inflamed gingival tissues. HIV+
      patients had, however, significantly higher CD4+/CD8+ ratios in gingiva than in
      peripheral blood (p < 0.05), indicating that CD4+ T cells are actively recruited
      to gingiva, even in cases of extreme CD4+ T lymphocytopenia.

PMID- 8537916
TI  - In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar
      bone resorption in rats.
AB  - The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on alveolar
      bone resorptive activity in rats were examined. Continuous administration of rhIL
      1 beta or phosphate-buffered saline (PBS) was given via osmotic pumps for 3, 7
      and 14 days to rats with silk ligatures around second maxillary molars. Other
      animals without ligatures received insertion of pumps containing rhIL-1 beta or
      remained untreated. Sections were subject to three different stains:--hematoxylin
      and eosin (H-E) for histology, acid phosphatase (ACPase) activity for osteoclast
      detection, and immunohistochemistry using anti-rat monocyte/macrophage monoclonal
      antibody (ED 1). In addition, body weight, plasma calcium and phosphorus levels
      were monitored. The mean body weight of rats receiving rhIL-1 beta was
      significantly lower (P < 0.05 to P < 0.01) compared with untreated rats
      throughout the experimental period. On Day 7, plasma calcium and phosphorus
      levels were significantly lower in rats receiving rhIL-1 beta than in rats
      receiving PBS only (P < 0.05). Sections revealed a moderate inflammatory cell
      infiltrate reaching near the alveolar crest in both groups with ligatures on Day
      3. Only rats receiving rhIL-1 beta exhibited enhancement of inflammatory cell
      invasion on Days 7 and 14. In rats receiving rhIL-1 beta with ligatures, numerous
      resorption lacunae containing ACPase-positive multinucleated giant cells (MNGCs),
      coinciding with ED1-positive cells, were located on the mesial side of the septum
      where extensive bone resorption had occurred throughout the experimental period.
      In animals receiving rhIL-1 beta without ligatures, compared with untreated rats,
      increased ACPase-positive cells were observed on the mesial side of the septum on
      Day 3. In animals receiving PBS only, a few ACPase-positive cells were observed
      confined to the mesial regions where slight bone resorption occurred on Days 7
      and 14. These results indicate that the administration of rhIL-1 beta accelerated
      alveolar bone destruction in ligature-induced periodontal tissue inflammation
      over a two-week period.

PMID- 8537917
TI  - Reliability of antagonistic arch impression in dental prostheses: clinical
      evaluation of different preimpression preparation procedures.
AB  - This study compared the influence of different methods of preimpression
      preparation on the quality of occlusal reproduction in irreversible hydrocolloid
      impressions. A total of 30 impressions of the lower dental arch of a patient were
      made with five different preimpression preparation procedures. Stone casts were
      made and analyzed. Critical comparison showed that the preimpression preparation
      influenced the quality of the occlusal surface of the cast. Fingerpainting the
      occlusal surface with fluid hydrocolloid before positioning the loaded impression
      tray, associated with use of a saliva ejector, reduced the incidence of
      macroscopic defects on the occlusal surface of the impressions.

PMID- 8537918
TI  - Effects of groove placement on retention/resistance of maxillary anterior resin
      bonded retainers.
AB  - Debonding of resin-bonded fixed partial dentures has been partly resolved with
      modification of tooth preparations. Tooth preparations for resin-bonded retainers
      were completed on a maxillary central incisor, a lateral incisor, and a canine.
      Fifteen metal replicas were constructed (five of each tooth morphotype). The
      three tooth morphotypes were then modified with proximal grooves prepared
      parallel to the long axes, and another 15 metal replicas were prepared. Cast
      metal retainers were constructed and cemented to the replicas with a resin
      cement. Tensile shearing dislodging loads were applied at 20 degrees to the long
      axes of the teeth with a testing machine. The addition of proximal grooves made
      statistically significant differences in resistance to debonding forces for all
      three tooth morphotypes (p < 0.01). An increase of 76.7% was seen in dislodging
      forces for lateral incisors with proximal grooves compared with incisors without
      grooves.

PMID- 8537919
TI  - A clinical evaluation of porcelain inlays.
AB  - Sparse data are available concerning the survival rate of porcelain inlays or
      onlays to inform the dentist and address the expectations of patients. A total of
      25 posterior porcelain inlays were inserted by two dentists at a private Danish
      clinic; the time elapsed since cementation was 20 to 57 months (average 40.4
      months). Tooth preparations for MOD porcelain inlays were completed for 13
      premolars and 12 molars but most did not include cuspal coverage. All inlays were
      constructed at the same commercial dental laboratory and according to the
      manufacturer's recommendations; they were etched and treated with silane before
      they were cemented. The cementation included etching of cavosurface enamel and
      treatment of the dentin with a dentinal bonding system. A thin layer of composite
      resin luting agent was applied to the tooth preparation before the porcelain
      inlays were cemented. The first 10 porcelain inlays were cemented with a light
      curing composite resin cement and the remaining 11 with a dual-curing composite
      resin cement. Twelve of the 25 porcelain inlays failed and were replaced during
      the observation period. Ten failures were due to a fracture of the inlay, one was
      caused by secondary caries, and the final failure was attributed to a marginal
      gap between the inlay and proximal tooth surface. Porcelain inlays cemented with
      light-curing composite resin exhibited more failures (p = 0.05) than those
      cemented with dual-curing composite resin. In addition, more failures (p = 0.07)
      were recorded among inlays inserted in molars than among those in premolars.

PMID- 8537920
TI  - Relative fracture toughness and hardness of new dental ceramics.
AB  - Dental ceramics can fail through growth of microscopic surface flaws that form
      during processing or from surface impact during service. New restorative dental
      ceramic materials have been developed to improve resistance to crack propagation.
      Eleven of these improved materials with the common feature of a considerable
      amount of crystalline phase in the glassy matrix were evaluated. The ceramic
      materials studied included fluormica-, leucite-, alumina-, and zirconia
      reinforced glasses. The relative hardness and fracture toughness were determined
      by indentation technique. Alumina-reinforced materials resulted in the highest
      fracture toughness values, whereas the fluormica- and leucite-reinfoced materials
      showed more moderate but statistically significant greater values compared with
      those of control materials. The hardness values of ceramic materials with
      improved fracture toughness were both substantially higher or lower than those of
      the control groups and suggested a lack of direct correlation between these two
      properties. Selection of appropriate restorative materials depends on clinical
      application and requires consideration of several physical properties including
      fracture toughness.

PMID- 8537921
TI  - Relationship between sandblasting and composite resin-alloy bond strength by a
      silica coating.
AB  - Modification of alloys for resin-bonded fixed partial dentures has been suspect
      since the introduction of the conservative procedure. This study investigated the
      effect of sandblasting on composite resin-alloy bond strengths with the
      Silicoating technique. Ag-Pd and Ni-Cr alloys were prepared for casting. The
      specimens then were sandblasted with 37 microns or 250 microns Al2O3 particles
      under the following conditions: 3 kg/cm2 for 30 seconds; 5 kg/cm2 for 10 seconds,
      30 seconds, and 45 seconds; and 7 kg/cm2 for 30 seconds. After each sandblasting
      treatment, the surfaces of the alloys were examined with the scanning electron
      microscope and the wettability of the alloy surfaces was measured. After
      sandblasting, the alloy surface was silica-coated, and light-cured composite
      resin then was bonded to the alloy. Specimens were divided, stored in dry air for
      1 week, and thermocycled from 4 degrees to 60 degrees C for 10(4) cycles. Bond
      strength was measured by applying compressive shear stress. It was found that
      sandblasting made the alloy-water contact angle smaller and wettability greater.
      The adhesive strength of composite resins with alloys was influenced by
      sandblasting.

PMID- 8537923
TI  - Food and Drug Administration requirements for dental implants.
AB  - The Food and Drug Administration (FDA) is a section of the Department of Health
      and Human Services of the United States Government, and its primary
      responsibility is to control the distribution of food, drugs, and medical devices
      within the country while ensuring public safety. The sale and distribution of
      dental implants is under the regulatory control of the FDA. Device
      classification, procedures for approval, and the current status of the approval
      process for endosseous implants are described in this article. The premarket
      approval procedure of the FDA is compared with the American Dental Association
      certification process. Issues related to the safety and effectiveness of dental
      implants are discussed.

PMID- 8537922
TI  - Twelve-month results of a clinical wear study of three artificial tooth
      materials.
AB  - This study compared in vivo wear of a new artificial tooth material with that of
      existing artificial tooth materials. Artificial tooth wear was determined by
      measuring height changes of selected points on contacting tooth surfaces in
      patients with complete dentures during a 12-month period. These results are part
      of an ongoing 3-year clinical study. A total of 67 patients were randomized to
      one of three treatment groups in this double-blind study. Group 1 received
      dentures with existing artificial tooth materials. Group 2 received dentures that
      contained teeth with the new experimental material. Group 3 received dentures
      with Bioform IPN resin teeth (Dentsply International Inc., York, Pa). A
      computerized coordinate measuring machine and computer-controlled X-Y positioning
      stages were used for this study. Tooth wear was determined by measuring vertical
      heights of contacting points from baseline points at each of two time intervals.
      The calculation of wear was made by comparing the differences in height at the
      beginning of the experiment with those measured at each time interval. A repeated
      measures analysis of variance (ANOVA) was used to test the difference in mean
      wear among the three groups from baseline to 6 months and from 6 to 12 months.
      Group differences in total wear at 12 months were also tested. The ANOVA results
      revealed no statistically significant differences in the wear among the three
      types of denture teeth at the 6- or 12-month time intervals or at 12 months (p >
      0.05). The average total wear value at 12 months was 90 microns. Group 1 averaged
      102 microns of wear, group 2 averaged 88 microns of wear, and group 3 averaged 76
      microns of wear.

PMID- 8537924
TI  - Synthetic casting tape as a facial impression tray material.
AB  - A procedure is described that uses thermoplastic synthetic casting tape for
      fabrication of facial impression trays. Once used, these trays can be disinfected
      without degradation of the tray material, which allows for storage and later use.

PMID- 8537925
TI  - A direct method for fabricating tongue-shielding stent.
AB  - During oral cancer radiotherapy, a tongue-shielding radiation stent guides the
      patient's upper and lower jaws to a repeatable position, attenuates radiation
      doses, and protects the tongue and structures adjacent to the irradiated field.
      Conventionally, a tongue-shielding radiation stent is made of heat-cured
      polymethyl methacrylate resin in which a low-melting Pb-Bi-Sn alloy is embedded
      as a shielding layer. Its use involves multiple and lengthy clinical and
      laboratory procedures. An improved polyvinyl siloxane-metal composite shielding
      system for radioprotection has recently been developed. This two-component, base
      and catalyst, putty material offers a shielding effect similar to that of the
      conventional shielding alloys. Its major advantages are that it is simple to use,
      requires only one clinical appointment, and affords efficient collaboration
      between dental and medical teams during cancer treatment. This article describes
      a simplified direct method of fabricating a tongue-shielding stent with the use
      of a new polyvinylsiloxane-metal composite in conjunction with impression putty
      material.

PMID- 8537926
TI  - A comparison of the effects of group function and canine guidance interocclusal
      device on masseter muscle electromyographic activity in normal subjects.
AB  - This study investigated the role of occlusal balance and canine guidance or group
      function guidance in masseter muscle function of normal subjects. Two types of
      interocclusal devices were constructed for each of the 10 subjects. Two ME 1020
      EMG analyzers and bipolar Ag/AgCI electrodes were used to record the
      electromyographic activity of masseter muscles during clenching in centric
      occlusion, during left and right laterotrusive movements, and during clenching at
      the extremities of the jaw both with the natural dentition only and with adjusted
      and intentionally unadjusted interocclusal devices in place. This study
      demonstrated that there was no difference in masseter muscle electromyographic
      activity between the use of interocclusal devices designed for canine guidance or
      for group function guidance in normal subjects. It showed also that altering the
      occlusal balance significantly reduced muscle activity.

PMID- 8537927
TI  - Surface characteristics of polyether and addition silicone impression materials
      after long-term disinfection.
AB  - It has been demonstrated that short-term disinfection can affect the surface
      properties of impression materials. This study evaluated advancing contact angle,
      receding contact angle, inhibition and mass loss of a polyether impression
      materials, and two different viscosities of an addition silicone impression
      material after long-term immersion disinfection (18 hours). The brand names of
      the impression materials tested were Impregum F, Extrude Extra, and Extrude Wash,
      and all were tested by use of the Wilhelmy technique; first, for the
      nondisinfected state, which served as controls, and then after 1 and 18 hours of
      disinfection in a full-strength solution of acid glutaraldehyde. Weight changes
      before and after the disinfection process were also measured to detect weight
      loss and mass change over time. All materials exhibited some degree of
      inhibition. Polyether lost 0.4% mass in air, which indicated loss of a volatile
      component. Polyether and addition silicone were both relatively hydrophobic and
      could be disinfected with acid glutaraldehyde for up to 18 hours without
      affecting wettability.

PMID- 8537928
TI  - Macromolecular leakage beneath full cast crowns. Part I: The diffusion of
      lipopolysaccharide and dextran.
AB  - Fifteen extracted molars were prepared for crowns. Crowns with access ports (one
      facial, one lingual) were cast in gold. Teeth and crowns with filters inserted
      into the ports were immersed in solutions of different concentrations of labeled
      and unlabeled macromolecules (fluorescein isothiocyanate-dextran,
      tetramethylrhodamine isothiocyanate-lipopolysaccharide [LPS], unlabeled LPS) and
      were evaluated for leakage. Retrieved filters were analyzed with fluorescent
      microscopy. At 10 micrograms/ml, only LPS leaked beneath the crowns in 24 hours
      (p = 0.0002), but after a 1-week immersion, both LPS and dextran leaked beneath
      the crowns. LPS scores were higher (p = 0.0002) than dextran scores. Slightly
      more LPS leakage occurred at 1 week than at 24 hours. LPS appeared to inhibit
      dextran diffusion beneath the cast crowns. Neither LPS nor dextran influenced LPS
      diffusion. Factors other than molecular size and weight may play a more important
      role in the microleakage occurring beneath crowns.

PMID- 8537929
TI  - A method to position replacement dies accurately on a fixed partial denture
      master working cast.
AB  - Impressions are often remade because of insufficient detail in one of many
      preparations. These impressions may be salvaged with a replacement die procedure.
      Some transfer or replacement die procedures fail to position the dies accurately;
      other procedures involve many steps in the fabrication of copings. This article
      describes a method that quickly and accurately positions a replacement die in a
      fixed partial denture master working cast.

PMID- 8537930
TI  - Precise trimming of soft lining materials with a hot instrument.

PMID- 8537931
TI  - Pouring a cast for immediate complete denture that simplifies setting of teeth.

PMID- 8537932
TI  - Controlling coloration for titanium restorations.

PMID- 8537933
TI  - Halothane and rouge: an alternative to chloroform and rouge as a disclosing
      medium.

PMID- 8537934
TI  - A dual-purpose, implant stent made from a provisional fixed partial denture.

PMID- 8537935
TI  - Topographic patterns of odorant receptor expression in mammals: a comparative
      study.
AB  - In a comparative study, molecular probes for various odorant receptor subtypes
      were employed in in situ hybridization experiments on tissue sections through the
      nose from different mammalian species. OR37 reactive neurons were found
      exclusively in the rodent species, where they were clustered in very similar
      position within the nasal cavities; an OR37-related receptor subtype was not
      detectable in the rabbit. All other subtypes tested, hybridized across species
      borders to neurons that were distributed within the distinct zones of the
      olfactory epithelium. Most receptor types were found in the same zone in all
      species; however, a few subtypes which are expressed in the medial zone in rat
      were found in the dorsal zone in guinea pig.

PMID- 8537937
TI  - Body temperature and behaviour of golden hamsters (Mesocricetus auratus) and
      ground squirrels (Spermophilus tridecemlineatus) in a thermal gradient.
AB  - Golden hamsters and thirteen-lined ground squirrels were maintained individually
      in a thermal gradient (14 degrees C to 33 degrees C) for several weeks under a
      14L:10D light-dark cycle. Animals of both species showed robust daily rhythms of
      body temperature and locomotor activity with acrophases consistent with the
      habits of the species (diurnal acrophases in the diurnal squirrels and nocturnal
      acrophases in the nocturnal hamsters). Hamsters showed a robust daily rhythm of
      temperature selection 180 degrees out of phase with the rhythms of body
      temperature and locomotor activity. Squirrels did not show a daily rhythm of
      temperature selection. These results raise the hypothesis that a daily rhythm of
      temperature selection is exhibited by nocturnal but not by diurnal endotherms.

PMID- 8537936
TI  - The whole-body shortening reflex of the medicinal leech: motor pattern, sensory
      basis, and interneuronal pathways.
AB  - The leech whole-body shortening reflex consist of a rapid contraction of the body
      elicited by a mechanical stimulus to the anterior of the animal. We used a
      variety of reduced preparations - semi-intact, body wall, and isolated nerve cord
      - to begin to elucidate the neural basis of this reflex in the medicinal leech
      Hirudo medicinalis. The motor pattern of the reflex involved an activation of
      excitatory motor neurons innervating dorsal and ventral longitudinal muscles
      (dorsal excitors and ventral excitors respectively), as well as the L cell, a
      motor neuron innervating both dorsal and ventral longitudinal muscles. The
      sensory input for the reflex was provided primarily by the T (touch) and P
      (pressure) types of identified mechanosensory neuron. The S cell network, a set
      of electrically-coupled interneurons which makes up a 'fast conducting pathway'
      in the leech nerve cord, was active during shortening and accounted for the
      shortest-latency excitation of the L cells. Other, parallel, interneuronal
      pathways contributed to shortening as well. The whole-body shortening reflex was
      shown to be distinct from the previously described local shortening behavior of
      the leech in its sensory threshold, motor pattern, and (at least partially) in
      its interneuronal basis.

PMID- 8537938
TI  - Effects of intracellular Ca2+ chelation on the light response in Drosophila
      photoreceptors.
AB  - In order to test the hypothesis that excitation in Drosophila photoreceptors is
      mediated by Ca2+ released from internal stores, the Ca2+ buffers EGTA, BAPTA and
      di-bromo-BAPTA (DBB) were introduced into dissociated photoreceptors via whole
      cell recording pipettes. All buffers were preloaded with Ca2+ to provide the same
      free Ca2+ concentration (250 nM). EGTA (up to 18 mM free buffer) had only weak
      effects upon voltage-clamped flash responses in normal Ringer's solution (1.5 mM
      Ca (2 0+)), and no effect in Ca2+ -free solution. The maximum BAPTA concentration
      tested (14.4 mM free BAPTA) reduced the initial rate of rise by ca. 5000-fold in
      normal Ringer's solution; by ca. 500-fold in Ca2+ free solution; and only ca. 60
      fold in the absence of Mg2+, which preferentially blocks one component of the
      light-sensitive current. Although BAPTA delayed the time-to-peak in normal
      Ringer's solution, responses in Ca2+ free Ringer's solution were accelerated.
      These results support the role of Ca2+ influx in regulating sensitivity and
      response kinetics; however, in view of the high concentrations required to
      attenuate responses in Ca2+ free Ringer's solution, the role of Ca2+ release in
      excitation remains unclear. DBB was ca. 2-3 fold more potent than BAPTA, and at
      concentrations > 5 mM had a qualitatively different action, greatly delaying the
      time-to-peak. This suggests DBB may have distinct pharmacological actions or
      access to compartments inaccessible to BAPTA. The only current activated by
      introducing 5-500 microM Ca2+ (buffered with nitrilo-triacetic acid) was
      electrogenic Na+/Ca2+ exchange. When this was blocked by removing Nao0+, a novel
      cationic conductance was activated. However, its properties did not resemble
      those the light-activated conductance, and thus do not support the hypothesis
      that Ca2+ is sufficient for excitation.

PMID- 8537939
TI  - Neural simulations of adaptive reafference suppression in the elasmobranch
      electrosensory system.
AB  - The electrosensory system of elasmobranchs is extremely sensitive to weak
      electric fields, with behavioral thresholds having been reported at voltage
      gradients as low as 5 nV/cm. To achieve this amazing sensitivity, the
      electrosensory system must extract weak extrinsic signals from a relatively large
      reafferent background signal associated with the animal's own movements.
      Ventilatory movements, in particular, strongly modulate the firing rates of
      primary electrosensory afferent nerve fibers, but this modulation is greatly
      suppressed in the medullary electrosensory processing nucleus, the dorsal
      octavolateral nucleus. Experimental evidence suggests that the neural basis of
      reafference suppression involves a common-mode rejection mechanism supplemented
      by an adaptive filter that fine tunes the cancellation. We present a neural model
      and computer simulation results that support the hypothesis that the adaptive
      component may involve an anti-Hebbian form of synaptic plasticity at molecular
      layer synapses onto ascending efferent neurons, the principal output neurons of
      the nucleus. Parallel fibers in the molecular layer carry a wealth of
      proprioceptive, efference copy, and sensory signals related to the animal's own
      movements. The proposed adaptive mechanism acts by canceling out components of
      the electrosensory input signal that are consistently correlated with these
      internal reference signals.

PMID- 8537940
TI  - A short red light pulse during dark phase of LD-cycle perturbs the hamster's
      circadian clock.
AB  - In this study we investigated the influence of red light< which naturally occurs
      during dawn and dusk, on locomotor activity and body temperature rhythms of
      Djungarian hamsters (Phodopus sungarus). A single weak red light pulse given 2 h
      before regular lights on had acute as well as long-term effects persisting for
      several days following exposure. The hamsters immediately stopped their locomotor
      activity, accompanied by a drop in body temperature. In the following undisturbed
      nights (ID 16:8) the nocturnal activity stopped earlier than usual. This lasting
      effect of the light pulse was more pronounced than the acute effect. The activity
      phase compressed gradually during 3 to 5 days after the light pulse was
      administered while time of activity onset was almost unaffected. It took 6 to 11
      days for complete recovery of the original activity phase. The maximal activity
      compression and the recovery period depended on the duration of the single red
      light pulse and its intensity. Red light pulses of 15 min duration were about
      twice effective as 1 min pulses; and the effect of a red light pulse of 130 mW/m2
      was about 1.5 times stronger than a 30 mW/m2 red light pulse. The maximal value
      of activity phase compression reached in this experiment was 2.5 + 0.2 h with a
      recovery period of 11.1 +/- 0.3 days following a given red light pulse of 90
      mW/m2 and 15 min. The "morning oscillator" seems to be persistently affected.
      This indicates a very high photosensitivity of the Djungarian hamster's circadian
      system to red light.

PMID- 8537941
TI  - Smoking in restaurants.

PMID- 8537942
TI  - Indian 'plague' epidemic: unanswered questions and key lessons.

PMID- 8537944
TI  - Climatic changes, mycotoxins, plagues, and genius.

PMID- 8537943
TI  - Equipoise and the ethics of randomization.

PMID- 8537945
TI  - Franz Liszt's eye disease.

PMID- 8537946
TI  - The skinache syndrome.
AB  - Chronic pain of unknown aetiology, and characterized by cutaneous trigger points,
      has been coined the skinache syndrome. The treatment of the skinache syndrome was
      evaluated in 94 patients by two independent methods 2 years after treatment.
      After one subcutaneous injection of lidocaine 68% of the patients were cured. The
      pain recurred in 27 patients having suffered for an average of 2 years. Surgical
      removal of the cutaneous trigger points cured 77% of the latter patients. The
      odds ratio of success of surgical treatment versus all other treatments combined
      was 101.3. The skinache syndrome requires a precise clinical investigation. Even
      when the origin of the pain in tendons, muscle and adipose tissue is excluded,
      the skinache syndrome remains a common, debilitating disorder. In contrast to
      fibromyalgia, the skinache syndrome has a simple and effective cure.

PMID- 8537947
TI  - The effects on prescribing patterns and costs of having a special interest in
      asthma.
AB  - To define the characteristics of general practices with a special clinical
      interest in asthma and to estimate the resulting extra prescribing costs, we sent
      a postal questionnaire to all English practices containing members of the General
      Practitioners in Asthma Group. Item and cost comparisons for 24 PACT (prescribing
      analysis and cost) aggregates were made between practices who had operated an
      agreed, written management plan for asthma before 1 April 1990 and all other
      practices in their respective Family Health Services Authorities. One hundred and
      sixty-three practices with GPIAG members responded (70%), of which 26 filled the
      management plan requirement. These 26 practices showed evidence of significantly
      better asthma care provision than the remainder of the sample. Their prescribing
      costs were significantly higher for respiratory drugs (median 37% higher) but
      lower in other drug categories. For respiratory drugs, costs were significantly
      higher for inhaled adrenoceptor stimulants, steroid inhalers, large spacers, and
      peak flow meters, but lower for cough medicines and systemic nasal decongestants:
      the number of items prescribed showed similar patterns. The prescribing costs of
      practices claiming a special interest in asthma are likely to show higher
      respiratory drug costs, but overall prescribing costs showed no increase in the
      practices studied.

PMID- 8537948
TI  - Iatrogenic damage to male reproductive function.

PMID- 8537949
TI  - Colonic trauma: modern civilian management and military surgical doctrine.
AB  - Colonic trauma, traditionally the domain of the military surgeon, has become
      commonplace in many parts of the world, where civilian surgeons have developed
      considerable experience with this complex type of injury. The author highlights
      the differences between military and civilian management concluding with an
      overview of current military research into battlefield colonic trauma. This paper
      reviews military surgical doctrine and summarizes the evolution in civilian
      surgical practice since the Second World War. South African management is
      discussed with reference to the author's travelling fellowship visit in 1993.
      Colonic trauma has been the subject of a military surgical research project,
      since 1992, with preliminary studies establishing an anastomotic technique
      suitable for use in the field. This work is summarized with an outline of the
      research programme.

PMID- 8537950
TI  - A patient's view of asthma.
AB  - A medical consultation is seen as a meeting between cultures which have developed
      from different standpoints. These cultures are described, as are the ways in
      which they may contribute to, or impede a full understanding between the doctor
      and the patient with asthma, or concerned parent.

PMID- 8537951
TI  - Peribulbar anaesthesia and needle length.
AB  - This retrospective audit of 87 consecutive patients undergoing routine cataract
      surgery compared the effect of peribulbar local anaesthesia using 16 mm and 25
      mm, 25 gauge needles to administer the anaesthetic. The effect on optic nerve
      function was observed. There was a significant increase of complete amaurosis in
      the group where the 16 mm needle had been used. This may be explained by more
      effective anatomic placement of the 16 mm needle within the orbit, allowing
      access to the retrobulbar space via fascial septae. There was significantly more
      lid akinesia with the 16 mm needle. None of this group required an additional
      facial nerve block, as opposed to 14% of the 25 mm needle group. The use of a 16
      mm needle is theoretically safer than a 25 mm needle to administer a peribulbar
      anaesthetic, in this review it was also demonstrated to be more effective.

PMID- 8537952
TI  - Ocular and renal sarcoidosis.
AB  - Sarcoidosis commonly presents in young adults with bilateral hilar
      lymphadenopathy, lung parenchymal disease and/or skin lesions. Ocular symptoms
      are the presenting feature in up to 10% of cases, but eye involvement can be
      demonstrated in around a quarter of all patients. Renal disease is much rarer,
      and may manifest with hypercalcaemic nephropathy, granulomatous interstitial
      nephritis, tubular dysfunction or glomerulonephritis. Eye and renal involvement
      are rarely found together, and may be confused with Wegener's granulomatosis or
      polyarteritis. We report a case of a young man who developed renal failure due to
      sarcoidosis soon after presenting with uveitis. The case illustrates an unusual
      combination of systemic features that may not be widely recognized.

PMID- 8537953
TI  - Anetoderma of Jadassohn-Pellizzari.
AB  - Anetoderma (derived from the Greek anetos, meaning slack) is a term used to
      describe localized increased laxity of the skin with herniation or outpouching,
      resulting from abnormal dermal elastic tissue. Primary anetoderma is distinctly
      rare. We describe a case where we suspect an auto-immune aetiology.

PMID- 8537954
TI  - Ethical committees.

PMID- 8537955
TI  - Placebo controls.

PMID- 8537956
TI  - Psychiatric aspects of hypopituitarism in adults.

PMID- 8537957
TI  - Standardization of botulinum toxin: scientific progress enhances animal welfare.

PMID- 8537958
TI  - Quantitative imaging of green fluorescent protein in cultured cells: comparison
      of microscopic techniques, use in fusion proteins and detection limits.
AB  - To determine the application limits of green fluorescent protein (GFP) as a
      reporter gene or protein tag, we expressed GFP by itself and with fusion protein
      partners, and used three different imaging methods to identify GFP fluorescence.
      In conventional epifluorescence photomicroscopy, GFP expressed in cells could be
      distinguished as a bright green signal over a yellow-green autofluorescence
      background. In quantitative fluorescence microscopy, however, the GFP signal is
      contaminated by cellular autofluorescence. Improved separation of GFP signal from
      HeLa cell autofluorescence was achieved by the combination of confocal scanning
      laser microscopy using 488-nm excitation, a rapid cut-on dichroic mirror and a
      narrow-bandpass emission filter. Two-photon excitation of GFP fluorescence at the
      equivalent of approximately 390 nm provided better absorption than did 488-nm
      excitation. This resulted in increased signal/background but also generated a
      different autofluorescence pattern and appeared to increase GFP photobleaching.
      Fluorescence spectra similar to those of GFP alone were observed when GFP was
      expressed as a fusion protein either with glutathione-S-transferase (GST) or with
      glucokinase. Furthermore, purified GST.GFP fusion protein displayed an extinction
      coefficient and quantum yield consistent with values previously reported for GFP
      alone. In HeLa cells, the cytoplasmic GFP concentration must be greater than
      approximately 1 microM to allow quantifiable discrimination over
      autofluorescence. However, lower expression levels may be detectable if GFP is
      targeted to discrete subcellular compartments, such as the plasma membrane,
      organelles or nucleus.

PMID- 8537959
TI  - New polarized light microscope with precision universal compensator.
AB  - A new type of polarized light microscope ('new pol-scope') for fast and
      orientation-independent measurement of birefringent fine structure has been
      developed. The design of the new pol-scope incorporates a precision universal
      compensator made from two liquid crystal variable retarders. A video camera and
      digital image processing system provide fast measurements of specimen anisotropy
      (retardance magnitude and azimuth) at all points of the image forming the field
      of view. The images document fine structural and molecular organization within a
      thin optical section of the specimen. The sensitivity of the current instrument
      is 0.1 nm of specimen retardance, measured with data gathered in 0.43 s at all
      640 x 480 image points. Examples of birefringence measurements in biological
      (microtubule arrays) and industrial (magneto-optical disc substrate) specimens
      are presented.

PMID- 8537960
TI  - Use of post mortem and in vitro tissue specimens for X-ray microanalysis.
AB  - Post mortem changes in the distribution of elements, as well as changes induced
      by dissection and incubation of tissue slices, were investigated by X-ray
      microanalysis of brain tissue, liver, pancreas and submandibular gland.
      Dissection itself causes minor changes in the intracellular ionic concentrations,
      but even a brief exposure of dissected tissue slices to a physiological buffer
      causes an increase in intracellular Na and Cl and a decrease in intracellular K
      concentration. The effect is most marked in brain tissue and least marked in
      submandibular gland slices. Incubation in fluid resembling the extracellular
      compartment in its ion composition results in a further increase of Na and Cl in
      brain tissue (cortex and hippocampus) and liver; in pancreas and submandibular
      gland, on the other hand, a stable situation throughout 2 h of incubation can be
      obtained. Incubation at lower temperature, and exchanging NaCl in the incubation
      medium for Na gluconate, has only relatively minor effects on the intracellular
      K/Na ratio. Exchanging the NaCl for K gluconate results in a high intracellular
      K/Na ratio throughout the incubation, but morphological evidence of tissue oedema
      was nevertheless observed. Physiological changes in intracellular ion content
      induced by cholinergic stimulation are similar in in vitro preparations as
      compared with stimulation in situ. The effect of dissection and brief incubation
      on the ionic composition of brain tissue is less pronounced 6 h after death than
      in a living, anaesthetized animal, but this is largely due to the post mortem
      changes that already have taken place.

PMID- 8537961
TI  - Adolescents as victims of family violence. Council on Scientific Affairs.
      American Medical Association.

PMID- 8537962
TI  - Television viewing and violence in children: pediatrician as agent for change.

PMID- 8537964
TI  - Physicians and domestic violence. Can we make a difference?

PMID- 8537963
TI  - Mississippi State Medical Association & Alliance Physician Resource Directory.
      Diagnostic & treatment guidelines on domestic violence.

PMID- 8537965
TI  - Color Doppler imaging of the eye and orbit.
AB  - 1. The use of color doppler imaging (CDI) in ophthalmology is a new and exciting
      area in vascular imaging. The physiologic information obtained and the anatomy
      evaluated has been inaccessible by any other noninvasive or invasive technique.
      2. Although CDI for ophthalmic use does not, as of this time, have FDA approval,
      clinical trials have begun. 3. It is our expectation that CDI will be an
      accurate, reproducible, noninvasive method to assist ophthalmologists in the
      diagnosis and treatment of patients with orbital and ocular vascular disease.

PMID- 8537966
TI  - Diplopia: the role of the ophthalmic medical assistant.
AB  - 1. One of the roles of the Ophthalmic Medical Assistant (OMA) is to provide the
      physician with as much clinical information as possible to assist in the
      diagnosis and management of patients whose chief complaint is "double vision". 2.
      Because diplopia can be associated with a variety of medical causes, it is
      important to obtain a very detailed medical, neurologic, and ocular history,
      along with examination of ocular motor function. 3. The OMA plays an important
      role in the evaluation of diplopia. The evaluation of diplopia can be complex,
      but, with proper assessment of the patient, most causes can be identified in the
      office.

PMID- 8537967
TI  - Visual field testing: pearls and pitfalls.
AB  - 1. Three major items are needed for a visual field test to take place: a
      perimetrist, a patient, and a request for a certain type of test. All of these
      are subject to knowledge of certain information and the ability to perform
      certain tasks. 2. The purpose of visual field testing is to provide information
      that will assist in diagnosing ocular diseases, evaluating neurologic diseases,
      and monitoring progression in ocular diseases. 3. The assessment of the patient's
      visual field is vital to his or her complete ocular examination. This diagnostic
      tool is very important and needs to be administered with professional technique
      and responsibility.

PMID- 8537968
TI  - Immunologic disorders of the sclera and conjunctiva.

PMID- 8537969
TI  - Fitting success with rigid gas-permeable lenses.

PMID- 8537970
TI  - Loss of functional beta 2-microglobulin in metastatic melanomas from five
      patients receiving immunotherapy.
AB  - BACKGROUND: In a subset of patients with metastatic melanoma, T lymphocytes
      bearing the cell-surface marker CD8 (CD8+ T cells) can cause the regression of
      even large tumors. These antitumor CD8+ T cells recognize peptide antigens
      presented on the surface of tumor cells by major histocompatibility complex (MHC)
      class I molecules. The MHC class I molecule is a heterodimer composed of an
      integral membrane glycoprotein designated the alpha chain and a noncovalently
      associated, soluble protein called beta2-microglobulin (beta 2m). Loss of beta 2m
      generally eliminates antigen recognition by antitumor CD8+ T cells. PURPOSE: We
      studied the loss of beta 2m as a potential means of tumor escape from immune
      recognition in a cohort of patients receiving immunotherapy. METHODS: We
      successfully grew 13 independent tumor cell cultures from tumor specimens
      obtained from 13 patients in a cohort of 40 consecutive patients undergoing
      immunotherapy for metastatic melanoma and for whom tumor specimens were
      available. These cell lines, as well as another melanoma cell line (called
      1074mel) that had been derived from tumor obtained from a patient in a cytokine
      gene therapy study, were characterized in vitro cytofluorometrically for MHC
      class I expression and by northern and western blot analyses for messenger RNA
      (mRNA) and protein expression, respectively, and ex vivo by immunohistochemistry.
      RESULTS: After one melanoma cell line (1074mel) was found not to express
      functional beta 2m by cytofluorometric analysis, four (31%) of the 13 newly
      established melanoma cell lines were found to have an absolute lack of functional
      MHC class I expression. Northern blot analysis of RNA extracted from the five
      cell lines exhibiting no functional MHC class I expression showed that these
      cells contained normal levels of alpha-chain mRNA but variable levels of beta 2m
      mRNA. In addition, no immunoreactive beta 2m protein was detected by western blot
      analysis. When human beta 2m was transiently expressed with the use of a
      recombinant vaccinia virus, cell-surface MHC class I expression was reconstituted
      and the ability of these five cell lines to present endogenous antigens was
      restored. Immunohistochemical staining of tumor sections revealed a lack of
      immunoreactive MHC class I in vivo, supporting the notion that the in vitro
      observations were not artifactual. Furthermore, archival tumor sections obtained
      from patients prior to immunotherapy were available from three patients and were
      found to be beta 2m positive. This result was consistent with the hypothesis that
      loss of beta 2m resulted from immunotherapy. CONCLUSIONS: These data suggest that
      the loss of beta 2m may be a mechanism whereby tumor cells can acquire
      immunoresistance. This study represents the first characterization of a molecular
      route of escape of tumors from immune recognition in a cohort of patients being
      treated with immunotherapy.

PMID- 8537971
TI  - Levamisole effects on major histocompatibility complex and adhesion molecule
      expression and on myeloid cell adhesion to human colon tumor cell lines.
AB  - BACKGROUND: The drug levamisole has been successfully used in combination with
      fluorouracil to increase the disease-free interval and survival of patients who
      have undergone surgical resection of Dukes' stage C colon cancer. Levamisole is
      thought to affect the host immune response. Several recent studies have examined
      its effect on the expression of major histocompatibility complex (MHC) class I
      molecules, but the results have been inconsistent. An equally important
      requirement for a host cellular immune response is the adhesion of leukocytes to
      tumor cells. The latter may be required for cell-mediated antitumor cytotoxic
      responses. PURPOSE: We evaluated the ability of levamisole to affect the
      expression of MHC class I molecules and cell-adhesion molecules and determined
      whether levamisole could affect leukocyte adhesion to tumor cells that had been
      treated with the drug. METHODS: A panel of four human colon tumor cell lines (HT
      29, SW-620, HCT-15, and LoVo), A-375 human melanoma cells, and human umbilical
      vein endothelial cells (HUVEC) were cultured in the presence of levamisole and
      examined by solid-phase enzyme immunoassay to determine the level of expression
      of MHC class I, intercellular adhesion molecule 1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1), leukocyte integrin VLA-4, and lymphocyte-functional
      antigen (LFA-1) molecules. Adhesion of HL-60 and THP-1 myeloid cells to tumor
      cells was also evaluated. Tumor necrosis factor (TNF) at 10 ng/mL was used as a
      positive control for increasing adhesion molecule expression and cell-cell
      adhesion. The statistical significance of differences in cell surface molecule
      expression and functional adhesion between treated and control cells were tested
      by use of analysis of variance and the two-tailed Dunnett's test. RESULTS:
      Treatment with levamisole (0.1 and 1 micrograms/mL) caused the levels of MHC
      class I expression to increase approximately threefold above control levels on
      HCT-15 and LoVo colon tumor cells (P < .05 in each case) compared with untreated
      cells, caused minimal increases on HT-29 cells (to 1.5 times control levels), but
      caused no significant increases on SW-620 colon tumor or A-375 melanoma cells.
      The HCT-15 and LoVo colon tumor cells had very low basal MHC expression
      Levamisole (1 micrograms/mL) increased VCAM-1 expression on HT-29 and SW-620
      colon tumor cells to 4.3 and 2.4 times (P < .05 in each case) control levels,
      respectively, doubled ICAM-1 expression on HT-29 cells (P < .05), and increased
      LFA-1 expression on HT-29, LoVo, and A-375 cells to 2.1, 3.2, and 1.8 (P < .05 in
      each case) times control levels, respectively. TNF (10 ng/mL) was used as a
      positive control and yielded increased expression of MHC class I molecules on the
      HT-29, LoVo, SW-620, and HCT-15 cells (2.5, 7.8, 1.9, and 4.8 times control
      levels, respectively; P < .05 in each case). TNF increased VCAM-1 expression to
      4.2 times the vehicle-treated control levels (P < .05) on HT-29 cells and
      increased ICAM-1 expression on HT-29, LoVo, and SW-620 cells (8.4, 1.8, and 1.9
      times vehicle control levels, respectively; P < .05 in each case). THP-1 and HL
      60 cells demonstrated increased adhesion to levamisole-treated HT-29 colon tumor
      cells. HL-60 cells also exhibited increased levamisole-mediated adherence to LoVo
      and HCT-15 cells. Adherence by THP-1 was significantly improved after levamisole
      treatment of the HUVEC, SW-620, and A-375 cells (P < .05 in each case).
      CONCLUSIONS: Levamisole can directly affect the expression and function of
      molecules that are engaged in cell-cell recognition and signaling on the surfaces
      of some tumor cell lines. However, no consistent pattern between cell-adhesion
      molecule expression, cell-cell adhesion, or levamisole concentration could be
      discerned.

PMID- 8537972
TI  - Telomerase activity in human breast tumors.
AB  - BACKGROUND: The activity of the ribonucleoprotein enzyme telomerase is not
      detected in normal somatic cells; thus, with each cell division, the ends of
      chromosomes consisting of the telomeric repeats TTAGGG progressively erode. The
      current model gaining support is that telomerase activity in germline and
      immortal cells maintains telomere length and thus compensates for the "end
      replication problem." PURPOSE: Our objective was to determine when telomerase
      activity is reactivated in the progression to malignant breast cancer and if
      knowledge of telomerase activity may be an indicator for the diagnosis and
      potential treatment of breast cancer. METHODS: Using a polymerase chain reaction
      based telomerase activity assay, we examined telomerase activity in 140 breast
      cancer specimens (from 140 patients), four phyllodes tumors (from four patients),
      38 noncancerous lesions (20 fibroadenomas, 17 fibrocystic diseases, one
      gynecomastia; from 38 patients), and 55 adjacent noncancerous mammary tissues
      (from 55 of the 140 breast cancer patients). In addition, 33 fine-needle
      aspirated breast samples (from 33 patients) were analyzed. RESULTS: Among
      surgically resected samples, telomerase activity was detected in 130 (93%) of 140
      breast cancers. Telomerase activity was detected in 68% of stage I primary breast
      cancers, in 73% of cancers smaller than 20 mm, and in 81% of axillary lymph node
      negative cancers. Moreover, the activity was detected in more than 95% of
      advanced stage tumors but in only two (4%) of 55 adjacent noncancerous tissues.
      While telomerase activity was not detected in any of 17 specimens of fibrocystic
      disease, surprisingly low levels of telomerase activity were detected in nine
      (45%) of 20 fibroadenomas. Among samples obtained by fine-needle aspiration, 14
      (100%) of 14 patients whose fine-needle-aspirated specimen contained telomerase
      activity and who subsequently underwent surgery were confirmed to have breast
      cancer. Multivariate analysis of 125 specimens from patients for whom data were
      available on age at surgery, stage of disease, tumor size, lymph node status
      tumor histology, and menopausal status indicated that stage classification
      exhibited the strongest association with telomerase activity (for stage I versus
      stages II-IV: odds ratio = 1.0 versus 73.4; 95% confidence interval = 2.0-959.0;
      P = .02). CONCLUSION: Telomerase activity was detected in more than 95% of
      advanced stage breast cancers. It was absent in 19%-32% of less advanced cancers.
      Since a determination of any association between telomerase activity and patient
      survival is not possible at the present time, it remains to be determined whether
      lack of telomerase activity predicts for favorable outcome.

PMID- 8537973
TI  - Chemoprevention of mammary carcinogenesis in the rat: combined use of raloxifene
      and 9-cis-retinoic acid.

PMID- 8537974
TI  - Prostate cancer--look to Denmark?

PMID- 8537975
TI  - Can mammographic densities predict effects of tamoxifen on the breast?

PMID- 8537976
TI  - Grist for the mill: role of cereal fiber and calcium in prevention of colon
      cancer.

PMID- 8537977
TI  - Caution guides genetic testing for hereditary cancer genes.

PMID- 8537978
TI  - Behavioral research initiatives given emphasis.

PMID- 8537979
TI  - Task force issues new screening guidelines.

PMID- 8537980
TI  - Joint venture strengthens U.S.-Europe cooperation on new cancer drugs.

PMID- 8537981
TI  - Move by FDA will speed approval of drugs across Europe.

PMID- 8537983
TI  - Consumption of black tea and cancer risk: a prospective cohort study.
AB  - BACKGROUND: Tea is one of the most frequently consumed beverages in the world.
      Antioxidant polyphenol compounds (such as catechins and flavonols) are abundantly
      present in both green and black teas and have been observed to have
      anticarcinogenic properties in cell and animal model studies. In black tea,
      however, most of the catechins have been oxidized to forms that may have reduced
      anticarcinogenic properties. Despite indications from experimental studies that
      tea may protect against cancer, epidemiologic evidence has been inconclusive.
      PURPOSE: The association between black tea consumption and the subsequent risk of
      stomach, colorectal, lung, and breast cancers was investigated in The Netherlands
      Cohort Study on Diet and Cancer among 58,279 men and 62,573 women aged 55-69
      years. METHODS: Subjects in the cohort completed a self-administered
      questionnaire on dietary habits and other risk factors for cancer at base line in
      1986. Follow-up for cancer was done by means of computerized record linkage with
      all nine regional cancer registries in The Netherlands and the national pathology
      database. During 4.3 years of follow-up, 200, 650, 764, and 650 cases of stomach,
      colorectal, lung, and breast cancers were diagnosed, respectively. The
      questionnaire data of case subjects and those of a random subcohort (n = 3500)
      were used to calculate rate ratios (RRs) of cancer in categories of consumers of
      black tea compared with nonconsumers. RESULTS: Tea was not used by 13% of the
      subjects in the cohort, whereas 37%, 34%, and 16% consumed one to two, three to
      four, and five or more cups of tea per day, respectively. No association was
      observed between tea consumption and risk of colorectal cancer: The risk among
      tea drinkers in each consumption category was similar to that among nondrinkers.
      The RR of breast cancer among consumers of five or more cups of tea per day was
      1.3 (95% confidence interval = 0.9-2.0); no dose-response association was
      observed. In age- and sex-adjusted analyses, consumption of tea was inversely
      associated with stomach (two-sided P for trend = .147) and lung (two-sided P for
      trend < .001) cancers. However, tea drinkers appeared to smoke less and to eat
      more vegetables and fruits than nondrinkers. When smoking and dietary factors
      were taken into account, tea in itself did not appear to protect against stomach
      and lung cancers: The RRs in all consumption categories were close to unity.
      Analysis of the tea and cancer relationship in a subgroup that included subjects
      in the lowest two quintiles of consumption of vegetables and fruits also failed
      to reveal a protective effect of tea consumption on the risk of three cancer
      types studied (colorectal, lung, and breast cancers). CONCLUSIONS: This
      investigation does not support the hypothesis that consumption of black tea
      protects against four of the major cancers in humans; a cancer-enhancing effect
      was not evident, either.

PMID- 8537982
TI  - Randomized, double-blinded, placebo-controlled study of effect of wheat bran
      fiber and calcium on fecal bile acids in patients with resected adenomatous colon
      polyps.
AB  - BACKGROUND: Ongoing epidemiologic and nutritional studies suggest that colorectal
      carcinogenesis is consistent with complex interactions between genetic
      susceptibility and environmental and dietary factors. Among the dietary
      components found to reduce colon cancer risk are high intakes of dietary fiber
      and calcium. PURPOSE: We designed and conducted a randomized, double-blinded,
      placebo-controlled trial involving supplementation of the customary dietary
      intake with fiber and calcium and measurements of fecal bile acids to examine the
      potential mechanisms by which added dietary interventions might reduce colorectal
      cancer risk. METHODS: In a randomized, double-blinded, phase II study, we used a
      factorial design to measure the effects of dietary wheat bran fiber (2.0 or 13.5
      g/day) in the form of cereal and supplemental calcium carbonate (250 or 1500
      mg/day elemental calcium) taken as a tablet on fecal bile acid concentrations and
      excretion rates. Measurements were made at base-line randomization (i.e., after a
      3-month placebo run-in period using 2.0 g wheat bran fiber plus 250 mg calcium
      carbonate) and after 3 and 9 months on treatment in a randomly selected 52
      patient subsample of the 95 fully assessable study participants who had a history
      of colon adenoma resection. Concentrations of fecal bile acids, total, primary
      (i.e., chenodeoxycholic and cholic), and secondary (i.e., deoxycholic,
      lithocholic, and ursodeoxycholic), were measured in 72-hour stool samples by gas
      liquid chromatography. All P values resulted from two-sided tests. RESULTS: All
      geometric mean fecal bile acid concentrations and excretion rates were lower at 9
      months than at 0 months or 3 months on treatment in the high-dose fiber, high
      dose calcium, and high-dose fiber/high-dose calcium treatment groups. The high
      dose fiber effect at 9 months of supplementation was statistically significant
      with respect to virtually all geometric mean fecal bile acid concentrations and
      excretion rates. For example at 9 months versus 0 months, high-dose fiber
      supplementation caused a reduction in fecal concentrations of total bile acids
      (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003). High
      dose calcium supplementation also had a significant, but lower, effect at 9
      months versus 0 months on the geometric mean total bile acid (35% reduction; P =
      .044) and deoxycholic fecal bile acid (36% reduction; P = .052) concentrations.
      CONCLUSIONS: High-dose wheat bran fiber and calcium carbonate supplements given
      for 9 months are associated with statistically significant reductions in both
      total and secondary fecal bile acid concentrations and excretion rates in
      patients with resected colon adenomas. This study supports the hypothesis that
      one of the important ways in which a high intake of wheat bran fiber and calcium
      may reduce the risk of colorectal neoplasia and cancer is by reduction of the
      concentrations of fecal bile acids. IMPLICATION: Phase III studies of these
      agents in the prevention of adenoma recurrence are necessary to confirm this
      hypothesis and have now been initiated at multiple institutions.

PMID- 8537984
TI  - Image- and model-based surgical planning in otolaryngology.
AB  - Preoperative evaluation of any operating field is essential for the preparation
      of surgical procedures. The relationship between pathology and adjacent
      structures, and anatomically dangerous sites need to be analyzed for the
      determination of intraoperative action. For the simulation of surgery using three
      dimensional imaging or individually manufactured plastic patient models, the
      authors have worked out different procedures. A total of 481 surgical
      interventions in the maxillofacial region, paranasal sinuses, orbit, and the
      anterior and middle skull base, in addition to neurotologic procedures were
      presurgically simulated using three-dimensional imaging and image manipulation.
      An intraoperative simulation device, part of the Aachen Computer-Assisted Surgery
      System, had been applied in 407 of these cases. In seven patients,
      stereolithography was used to create plastic patient models for the preparation
      of reconstructive surgery and prostheses fabrication. The disadvantages of this
      process include time and cost; however, the advantages included (1) a better
      understanding of the anatomic relationships, (2) the feasibility of presurgical
      simulation of the prevailing procedure, (3) an improved intraoperative
      localization accuracy, (4) prostheses fabrication in reconstructive procedures
      with an approach to more accuracy, (5) permanent recordings for future
      requirements or reconstructions, and (6) improved residency education.

PMID- 8537985
TI  - Prevention of noise-induced hearing loss in the Canadian military.
AB  - A prospective study was undertaken to investigate the development of noise
      induced hearing loss in Canadian military recruits, and to assess the
      effectiveness of the hearing conservation program currently in place. The
      participants were 134 men and women, 20 to 30 years of age, employed in four
      trades, three of these (infantry, artillery, and armour) associated with high
      noise levels. The data comprised audiometric measurements made at the time of
      entry and after 3 years of employment, and responses to a questionnaire mainly
      relating to noise exposure in the workplace and during leisure activities, and
      the utilization of personal hearing protective devices. The findings showed that
      group audiograms at entry and at the 3-year recall were characterized by a 6-kHz
      notch that was indicative of noise-induced hearing loss, although mean threshold
      values were within normal limits. By the 3-year recall, 11% of the infantry had
      sustained a mild-to-moderate hearing loss in the left ear, greater than 25-dB HL,
      that was consistent with the use of small-calibre weapons. Responses to the
      questionnaire indicated that, while subjects appreciated the potential benefit of
      wearing hearing protectors, instructions in their proper use and education on the
      hazards of noise exposure were poor. The results suggested methods to strengthen
      the existing scheme for hearing conservation to further minimize risk.

PMID- 8537987
TI  - Laryngeal mask airway in paediatric otolaryngologic surgery.
AB  - The laryngeal mask airway (LMA) is a relatively recent development that fills the
      gap in airway management between endotracheal intubation and the use of a face
      mask. The device is inserted blindly into the pharynx, forming a low-pressure
      seal around the laryngeal inlet permitting gentle positive-pressure ventilation.
      It allows the administration of inhaled anaesthetic agents through a minimally
      stimulating airway. This factor, combined with its ease of insertion, suggested
      that the laryngeal mask airway might offer some distinct advantages in
      otolaryngologic paediatric surgery. Our experience in utilizing the laryngeal
      mask in tonsillectomy and adenoidectomy, and in myringotomies with insertion of
      ventilating tubes is described, and its advantages and disadvantages are
      discussed.

PMID- 8537988
TI  - Incentive spirometry for tracheostomy and laryngectomy patients.
AB  - Sustained maximal inspiration (incentive spirometry) is used for the prevention
      and management of atelectasis in major abdominal and thoracic surgery. Patients
      with head and neck surgery are predisposed to postoperative disturbances in lung
      function after extensive surgical resection, immobilization, or significant chest
      wall deformity from various reconstructive procedures. The patient often requires
      tracheostomy or permanent laryngeal stoma. A prospective clinical study on
      patients with major head and neck surgery was conducted to evaluate the use of
      incentive spirometry to improve postoperative lung function. An adaptor was first
      designed to allow patients with tracheostomy tubes to use the spirometers.
      Parameters studied include vital signs, arterial blood gases (A-a gradient), and
      pulmonary function test. Significant improvement of lung function and lack of
      complication warrant the use of incentive spirometry in postoperative head and
      neck surgery patients.

PMID- 8537986
TI  - Short-term results of laryngeal framework surgery--thyroplasty type 1: A pilot
      study.
AB  - This article prospectively analyses 10 patients with a unilateral vocal cord
      paralysis who were nonrandomly selected for laryngeal framework surgery. Pre- and
      postoperative videolaryngoscopic, acoustic, and laryngeal airflow recordings of
      each patient's voice were taken and compared with the patient's own subjective
      analysis of his/her voice. Results indicate that laryngeal framework surgery
      using the surgical technique described in this paper gives a statistically and
      clinically improved voice in the short term.

PMID- 8537989
TI  - Proximal pH-metry for diagnosis of upper airway complications of gastroesophageal
      reflux.
AB  - Otolaryngologic complications of gastroesophageal reflux (GER) are well described
      in adults, but this relationship has not been as carefully studied in children.
      We reviewed 26 dual pH-probe studies performed on 22 children with upper airway
      symptoms. The proximal probe was placed in the nasopharynx or hypopharynx. The
      distal probe was placed in the mid-proximal oesophagus. The proximal recording
      was considered normal if no episodes of pH < 4 were recorded. Indications for the
      studies were upper airway obstruction (UAO) and congenital choanal atresia (CCA).
      The age range was from 2 weeks to 47 months. The distal pH probe study was normal
      in 13 of 22 patients overall. Seventeen UAO patients had abnormal proximal pH
      probe studies. After treatment, 16 of 17 had improved airways. Twelve with UAO
      (67%) were premature and/or had developmental delay. Three CCA patients had
      abnormal proximal pH-probe studies and all improved after treatment. Four follow
      up pH studies were normal or improved. GER-induced UAO is more frequent in
      infants or children with a history of prematurity or developmental delay.
      Proximal pH-metry is a useful technique to document the relationship between
      upper airway symptoms and GER. Patients with GER-induced UAO should undergo
      endoscopy to rule out simultaneous airway lesions.

PMID- 8537990
TI  - Treatment of haemorrhagic telangiectasia with the flashlamp-pulsed dye laser.
AB  - The management of epistaxis in patients with hereditary haemorrhagic
      telangiectasia (Osler-Weber-Rendu) is often a perplexing problem. In the past,
      cautery, cryosurgery, and septodermoplasty have all been used with varying
      degrees of success. The Candela flashlamp-pulsed dye laser was developed for
      management of vascular lesions (port-wine stains and telangiectasia). The results
      of our prospective trial utilizing this laser in the treatment of intranasal
      telangiectasia in patients with hereditary haemorrhagic telangiectasia are
      presented.

PMID- 8537991
TI  - Snoring: a review and a reassessment.
AB  - The pathophysiology of snoring is discussed and the etiologic importance of nasal
      obstruction and compliance of the pharynx with respiratory airflow pressures are
      questioned. The discrepancy between subjective and objective results of therapy
      is noted and wider use of objective measurement pre- and post-snoring treatment
      is advocated.

PMID- 8537992
TI  - Tuberculous tonsillitis.
AB  - The epidemiology of tuberculosis has changed recently with an increasing
      incidence of unusual presentations. A case of tuberculous tonsillitis, which is a
      rare condition, is presented in this report. The manifestations of this entity
      are tonsillar hypertrophy and painful ulceration. Final diagnosis of tuberculous
      tonsillitis is usually made after histopathologic examination of tonsillectomy
      material. Cultures should be obtained from the tissue specimens, and acid-fast
      bacilli must be investigated to confirm the diagnosis. Systemic signs of
      tuberculosis may not be seen in this clinical form. These features may confuse
      tuberculous tonsillitis with malignancies. In this article, general information
      and literature about tuberculous tonsillitis are reviewed, and a case of
      tuberculous tonsillitis is reported to draw attention to this rare clinical form
      of tuberculosis.

PMID- 8537993
TI  - Perinatal management of nasopharyngeal teratoma.
AB  - Nasopharyngeal teratoma is a rare benign entity, with most of the published
      literature represented by sporadic case reports. We present a recent case of a 23
      year-old woman found to have elevated maternal serum alpha-fetoprotein and
      ultrasound findings of a fetal cystic mass in the mandibular region. The infant
      had a large nasopharyngeal teratoma protruding from the oral cavity making airway
      access extremely difficult. The presence of severe coexisting cardiac anomalies
      and respiratory disease led to death in the neonatal period. This report and the
      review of the literature stress the importance of recognizing suggestive prenatal
      data and preparing for perinatal management including maintenance of fetal
      oxygenation and aggressive early provision of an adequate airway.

PMID- 8537994
TI  - Ethmoidal myofibroblastoma.
AB  - Myofibroblastoma is an uncommon mesenchymal tumour characterized by spindle cells
      exhibiting the ultrastructural and immunohistochemical features of
      myofibroblasts. We report a case of a myofibroblastoma occurring in the ethmoid
      sinus, which to our knowledge is the first case reported in the literature. The
      clinical presentation, diagnosis, histology, and management of this lesion is
      discussed with a review of the relevant literature.

PMID- 8537995
TI  - Tuberculosis of the nasal fossa manifested by a polypoid mass.
AB  - Since the introduction of effective antituberculous chemotherapy, upper
      respiratory tract tuberculosis is infrequent; nasal involvement is a very rare
      form of this disease. In this localization, tuberculosis is usually unilateral
      and typically discloses a definite granular mass or an ulcer. We report a case
      manifested by an intranasal mass on computerized tomography scans that evolved as
      chronic rhinitis.

PMID- 8537996
TI  - Multiple oncocytic laryngeal cysts presenting as acute airway obstruction.
AB  - Solitary oncocytic cyst of the larynx is a recognized clinical and pathologic
      entity. Multiple oncocytic cysts have only rarely been described. A 67-year-old
      female presented with rapidly progressive airway obstruction requiring emergency
      tracheotomy. The obstruction was caused by multiple cystic lesions throughout the
      supraglottic region. Microscopic examination of laryngeal biopsies showed cysts
      within the lamina propria, lined by oncocytic epithelium. The differential
      diagnosis and pathogenesis of oncocytic cysts is discussed with a review of other
      laryngeal cystic lesions.

PMID- 8537997
TI  - [Cerebral oxygen saturation (rSo2) during open heart surgery and postoperative
      brain dysfunction].
AB  - We studied the occurrence of brain dysfunction in regards to changes in cerebral
      oxygen saturation (rSo2) during open heart surgery. The subjects were 68 patients
      with the average age of 61 years. For the evaluation of brain function, Hasegawa
      Dementia Scale was used, and those patients whose scores were less than 23
      points, or had decreased by more than 3 points from preoperative scores on the
      7th postoperative day were categorized as the brain dysfunction group. There were
      14 (21%) postoperative brain dysfunction cases. Although rSo2 values during
      surgery ran at 70-65% level, the brain dysfunction group showed significantly
      lower values throughout the entire procedures, with the lowest value being 61%
      during cardiopulmonary bypass. The patients in the dysfunction group were of
      older ages and postoperative lower cardiac index, which indicated that the
      occurrence of brain dysfunction is greatly influenced by low cerebral blood flow.
      Effect from the operative procedures and CPB alone seemed to be small. Cerebral
      oxygen saturation (rSo2) is believed to be a useful monitor of cerebral blood
      flow, and occurrence of brain dysfunction may be expected at values lower than
      60%.

PMID- 8537998
TI  - [Relationship between retained microbubbles and neuropsychologic alterations
      after cardiac operation].
AB  - We studied the relationship between quantity of microbubble retained in the left
      heart and neuropsychologic alterations after surgery in 21 patients undergoing
      cardiac surgery including cardiopulmonary bypass. The neuropsychologic change was
      evaluated by three kinds of psychological test, which mainly analyzed memory and
      cognition. The microbubble was continuously monitored by the long axis view of
      the descending aorta of transesophageal echocardiography and then quantitatively
      analyzed and graded by the on-line computer. More microbubbles were detected in
      the valve surgery requiring the intracardiac procedure than in coronary artery
      bypass grafting and neuropsychologic deterioration, although the relationship did
      not reach statistical significance. Since most of the microbubbles were detected
      during the unclamping of aorta and the weaning from cardiopulmonary bypass, a
      technical improvement of the surgical procedures could reduce them. We think that
      transesophageal echocardiography is useful for monitoring microbubbles during
      operation.

PMID- 8537999
TI  - [Serum cardiac troponin-T in coronary artery bypass graft and mitral valve
      replacement].
AB  - Serum cardiac troponin-T was measured to evaluate perioperative myocardial injury
      in heart surgery. Twelve patients of coronary artery bypass graft (CABG) and nine
      of mitral valve replacement (MVR) were selected and the measurements were
      performed at 3 points-before, as well as after the surgery and on the first
      postoperative day. Elevated serum levels of troponin-T were observed in
      postoperative measurement in both groups (CABG 2.98 +/- 1.44, MVR 2.57 +/- 0.52
      ng.ml-1), where all the preoperative values were less than 0.1 ng.ml-1. On the
      first postoperative day, CABG group showed a higher serum level of troponin-T
      than MVR group (6.05 +/- 4.16 vs. 2.57 +/- 2.12 ng.ml-1, P < 0.05 respectively).
      Taking another myocardial marker, such as CK-MB or myosin light chain I, into
      consideration, these data indicate that myocardial injury occurs during heart
      surgery and the grade of injury is severer in CABG than in MVR.

PMID- 8538000
TI  - [Does a tracheal bifurcation shift upward due to increased intraabdominal
      pressure during laparoscopic surgery?].
AB  - To evaluate the influence of increased intraabdominal pressure on a position of
      tracheal bifurcation, we measured the distance from the tracheal bifurcation to
      the tip of the endotracheal tube which is fixed on a patient's mouth during a
      laparoscopic surgery. The distance decreased from 3.5 +/- 1.9 to 3.1 +/- 1.9 cm
      (P < 0.05) at mean intraabdominal pressure of 8.7 mmHg. This result suggests that
      the ventilation may become difficult due to the occlusion of the tip of the
      endotracheal tube by a tracheal bifurcation or due to inadvertent single lung
      ventilation under inappropriately deep intubation.

PMID- 8538001
TI  - [The effects of treatment with lipopolysaccharide on responsiveness of rat blood
      vessels].
AB  - Effects of treatment with lipopolysaccharide (LPS) both in vivo (intraperitoneal
      administration of 20 mg.kg-1 LPS for 6 hours) and in vitro (incubation with 1
      microgram.kg-1 LPS for 6 hours) on the responsiveness of the rat thoracic aorta,
      carotid, renal, femoral, mesenteric, pulmonary arteries, and the femoral and
      mesenteric veins were examined. Intraperitoneal administration of LPS did not
      change the blood pressure of rats, but increased the heart rate significantly.
      The same amplitude of relaxation was produced by L-arginine in the aortic strips
      treated by LPS in vivo and in vitro, and the responses were inhibited by NG-nitro
      L-arginine (L-NOARG). The contractile responses to phenylephrine in the aortic
      strips were reduced by LPS-treatment in vivo or in vitro, but the extent of
      inhibition was greater in vivo than in vitro. Further, the attenuation of
      contractile responses to phenylephrine was completely reversed by L-NOARG in the
      strips treated with LPS in vitro, whereas the reversal by L-NOARG was incomplete
      in the strips treated with LPS in vivo. Different amplitudes of relaxations were
      also produced by L-arginine or SNP in the blood vessels treated by LPS in vivo or
      in vitro. However, the tail artery treated with LPS in vivo or in vitro did not
      relax in response to L-arginine but did produce a relaxation to SNP. These
      results suggest that the hyporesponsiveness of rat blood vessels after treatment
      with LPS in vivo or in vitro may be related to an enhanced NO production in the
      smooth muscle cells and that there is a possible heterogeneity of regional
      induction or activation of L-arginine/NO pathway by LPS in rat blood vessels.

PMID- 8538002
TI  - [The effects of prostaglandin E1 and epidural anesthesia on peripheral blood
      flow].
AB  - We compared the effects of prostaglandin E1 (PGE1) and epidural anesthesia on
      peripheral blood flow by laser Doppler tissue flowmetry during lower abdominal
      surgery. Epidural anesthesia increased the blood flow of the toe, where the
      sympathetic nerve supply is of the same spinal cord segments as that of pelvic
      organs. On the other hand, PGE1 could not prevent the decrease of the blood flow
      of the toe, but increased that of the index finger, which did not receive the
      nociceptive stimuli from operative site. Thus, the use of epidural anesthesia
      together with PGE1 is considered to be effective to increase peripheral blood
      flow.

PMID- 8538003
TI  - [Effects of systemic lidocaine, mepivacaine and bupivacaine on passive avoidance
      learning in mice].
AB  - The effects of local anesthetics on learning were assessed in mice through one
      trial step-through passive avoidance performance. Lidocaine HCl (10, 20 or 40
      mg.kg-1), mepivacaine HCl (15, 30 or 60 mg.kg-1) or bupivacaine HCl (2.5, 5 or 10
      mg.kg-1) were injected subcutaneously 10 min before acquisition training.
      Lidocaine, but not mepivacaine and bupivacaine, reduced the latency in the
      retention trial conducted 24hr after the training in a dose-dependent manner.
      However, lidocaine did not alter the latency when it was given 10 min before the
      retention trial. These results suggest that lidocaine impairs acquisition, but
      not retention or retrieval phase in the memory process.

PMID- 8538004
TI  - [Effect of preoperative treatment with recombinant human erythropoietin in
      patients undergoing hemodilutional autologous transfusion].
AB  - This study evaluated whether a combination of recombinant human erythropoietin
      (rHuEPO) and hemodilutional autologous transfusion could reduce homologous blood
      transfusion in 37 patients who underwent elective urological surgery. A single
      dose of 6000 IU rHuEPO was administered 2 weeks before operation to patients
      whose preoperative hemoglobin was less than 12.0 g.dl-1 (8.5-12.0 g.dl-1) (EPO
      group, n = 15) and compared these with control subjects whose preoperative
      hemoglobin was more than 12.0 g.dl-1 (non-EPO group, n = 22). Both hemoglobin and
      hematocrit levels after administration of rHuEPO in the EPO group increased
      significantly to the same levels as in those in the non-EPO group and remained at
      these levels. The mean volume of donated autologous blood was 980 g in the EPO
      group and 110 g in the non-EPO group. The mean surgical blood loss was 1330 g in
      the EPO group and 1120 g in the non-EPO group. No homologous blood transfusion
      was required in 80 percent of the cases in both groups: however, homologous
      transfusions were added to 3 cases in the EPO group and 4 cases in the non-EPO
      group whose surgical blood loss was over 2500 g. We conclude that the combination
      of preoperative rHuEPO treatment and hemodilutional autologous transfusion can
      reduce homologous transfusion during surgery in anemic patients.

PMID- 8538005
TI  - [The effect of cardiopulmonary bypass on the cardiopulmonary function after open
      heart surgery].
AB  - The effect of cardiopulmonary bypass (CPB) on the cardiopulmonary function after
      open heart surgery was evaluated by multiple regression analysis in relation with
      preoperative factors. In cases without decompensated heart failure, the
      depression of cardiac function and its recovery after CPB were mostly related to
      cross-clamp time. The pulmonary oxygenation was affected with operation time, and
      the duration of artificial ventilation correlated with CPB time. From these
      results, we conclude that CPB is the most important factor determining the
      cardiopulmonary function after CPB.

PMID- 8538007
TI  - [Anesthesia for funnel chest operation].
AB  - The incidence of perioperative complication and days of hospital stay were
      studied in 56 patients with funnel chest operation under inhalational anesthesia
      (18 cases), intravenous anesthesia (23 cases) and epidural anesthesia (15 cases).
      Perioperative complication occurred most frequently in the inhalational group and
      was followed by intravenous and epidural group. Postoperative hospitalization on
      an average was 21.4 days in the inhalational group, 21.9 days in the intravenous
      group and 16.7 days in the epidural group. It is said that postoperative pain
      leads to splinting of the chest, which can cause atelectasis and/or pneumonia.
      Severe postoperative pulmonary complication was reduced in the epidural groups.
      As a result, hospitalization in the epidural group was shorter than in other
      groups. This study suggests that epidural anesthesia is more advantageous for
      funnel chest operation because epidural anesthesia has protective action against
      arrhythmia and postoperative pulmonary complication.

PMID- 8538006
TI  - [Subdural catheterization uncovered by severe hypotension during epidural plus
      general anesthesia].
AB  - We experienced three cases of accidental subdural catheterization during epidural
      combined with general anesthesia. In each case, epidural catheterization was
      performed before induction of general anesthesia. Aspiration through the catheter
      and a response to a test dose were negative. Then anesthesia was induced with
      thiamylal IV and the trachea was intubated with vecuronium IV. Hypotension, which
      was not easily treated by vasopressors and volume load, occurred after
      administration of 3 to 8 ml mepivacaine with 1: 200,000 epinephrine through the
      catheter. We examined position of the catheter by injecting iohexol 240 and
      confirmed subdural catheterization after surgery. It is often difficult to
      identify subdural placement of an epidural catheter under general anesthesia
      since signs of massive sensory blockade are masked by general anesthesia. In each
      case, we suspected malpositioning of the catheter by severe hypotension due to
      sympatholysis which was difficult to treat. Subdural catheterization is a
      complication of epidural anesthesia that probably occurs more frequently than
      previously recognized and is usually unpredictable during general anesthesia.

PMID- 8538008
TI  - [A case in which the endotracheal tube was ignited by an electrocautery during
      tracheotomy].
AB  - Electrocautery is essential in the modern operation. But if we use it carelessly,
      a severe complication can occur. Tracheotomy was performed by surgeons after
      laparotomy and drainage in a patient with severe pancreatitis. Endotracheal tube
      was ignited during hyperoxidation immediately after trachea was incised by
      electrocautery. Trachea and bronchi was damaged by heat. After the tracheotomy we
      examined his trachea and bronchi with a bronchoscope periodically. Electrocautery
      should be used carefully during hyperoxidation.

PMID- 8538009
TI  - [Anesthetic management of a Paget's disease patient complicated with Parkinson
      disease].
AB  - Paget's disease is a metabolic disorder of unknown etiology characterized by
      excessively rapid remolding of bone. We report a case of Paget's disease
      complicated with Parkinson syndrome. A 69-year-old female patient was scheduled
      for ventriculo-peritoneostomy due to hydrocephalus. Her manifestations included
      disability to walk, slight deafness and muscular rigidity of limbs, without
      symptom of intracranial hypertension. After induction of anesthesia with
      thiopental and vecuronium, tracheal intubation with Macintosh laryngoscope was
      attempted but failed because mouth opening was restricted to only 3 cm. Again
      with Bullard laryngoscope, she was successfully intubated. During neurosurgical
      operation, the anesthesia was maintained with low concentration of isoflurane
      (under 0.3%), nitrous oxide and oxygen. The surgery was completed without adverse
      events such as disorder of autonomic nervous system. However 6-days after
      operation, ventilatory arrest occurred due to bronchial obstruction with sputum.
      Immediately, re-intubation was performed without any sequela and tracheostomy was
      also performed. In conclusion, as reported previously, intubation and
      postoperative pulmonary dysfunction should be carefully taken care of, and
      Bullard laryngoscope was useful for this patient.

PMID- 8538010
TI  - [Anesthesia with transesophageal echocardiography for removal of
      pheochromocytoma].
AB  - A 45-year-old female was scheduled for left adrenalectomy because of a
      pheochromocytoma. Preoperative general condition was well controlled with alpha-
      and beta-blockers. Anesthesia was induced with thiamylal and vecuronium, and
      maintained with isoflurane (0.5-3%) and nitrous oxide in oxygen. Blood pressure
      was controlled with nicardipine and alpha-blocker during the manipulation of the
      tumor. After removal of the tumor, dopamine and norepinephrine were used. We used
      transesophageal echocardiography (TEE) to determine the fluid administration rate
      and doses of catecholamine. We could observe the wall motion and the mass of the
      heart, and see changes of the left ventricular enddiastolic volume, the cardiac
      output and the stroke volume. TEE monitoring seems to be very useful during the
      resection of pheochromocytoma.

PMID- 8538011
TI  - [A case of sudden death during postoperative Holter ECG examination in a patient
      who experienced intraoperative cardiac arrest].
AB  - We report a case of postoperative sudden death during Holter-ECG examination in a
      62-yr-old male, who experienced intraoperative cardiac arrest possibly due to
      myocardial ischemia. Although the patient recovered from intraoperative event
      without any neurological sequelae, he suffered from spontaneous ventricular
      tachycardia following mild ST segment depression that led to cardiac arrest on
      the 58th postoperative day. Precise mechanism of sudden death was not clear
      because coronary angiography or autopsy was not performed. However, the
      postoperative Holter-ECG revealed frequent episodes of silent 0.5-1.0 mm ST
      segment depression during tachycardia which had not been observed in the
      preoperative 12-lead ECG. Thus a likely explanation would be that the patient had
      the undetected coronary artery disease with frequent episodes of silent ischemia
      and finally was led to the fatal arrhythmia. In this case, so called "stunned
      myocardium" following repeated silent ischemia may have also contributed to the
      life-threatening arrhythmias. This case suggests that even mild ST depression
      might lead to life-threatening arrhythmias in the patients with silent ischemia.
      Adequate preoperative evaluation and careful perioperative observation are
      necessary for these patients.

PMID- 8538012
TI  - [Four cases of noncardiac surgery after PTCA].
AB  - Malignant tumors were detected in four patients who had been hospitalized for
      acute myocardial infarction and/or postinfarction angina. All of them underwent
      curative operations after successful percutaneous transluminal coronary
      angioplasty (PTCA). Operations performed were partial colectomy on the first
      patient, low anterior rectal resection on the second patient, left pulmonary
      upper lobectomy on the third patient and partial colectomy with cholecystectomy
      on the fourth patient. There were no complications in the perioperative periods
      except the first patient in which postoperative electrocardiogram showed
      transient peaked T wave in leads II, III, AVf, V5 and V6. Forty six days after
      colectomy (55 days after PTCA), the first patient underwent emergency PTCA for
      restenosis. Prior PTCA, as well as CABG, is considered to have decreased cardiac
      complications in patients with ischemic heart disease. But when a non-cardiac
      operation should be done after PTCA, we should take restenosis into
      consideration.

PMID- 8538013
TI  - [Cardiopulmonary resuscitation with continuous veno-venous hemofiltration for
      intraoperative cardiac arrest owing to hypothermia--a case report].
AB  - A 77-year-old female was scheduled for an exploratory laparotomy under nitrous
      oxide-oxygen-neurolept anesthesia. At the time of admission to the operating
      room, the rectal temperature was 36.0 degrees C. From the beginning of operation,
      the body temperature dropped slowly despite constant efforts of warming with a
      blanket and warm intravenous fluids. At 5 hours and 15 minutes after the
      beginning of operation, she developed cardiac arrest due to hypothermia. At this
      time the rectal temperature was 31.8 degrees C. In spite of cardioversion and
      intravenous administration of epinephrine, we could not resuscitate her
      successfully. Immediately, rewarming was started with continuous veno-venos
      hemofiltration (CVVH). When the rectal temperature rose to 32.9 degrees C one
      hour after the rewarming, cardioversion was performed again and spontaneous heart
      beat was observed. As soon as the rectal temperature rose to 34.0 degrees C, CHF
      was stopped. Her consciousness recovered 2 hours and 10 minutes after
      cardiopulmonary resuscitation, we conclude that rewarming with CVVH can be an
      effective method of cardiopulmonary resuscitation in a patient suffering cardiac
      arrest due to hypothermia.

PMID- 8538014
TI  - [A case of inspiratory unidirectional value malfunction detected by an abnormal
      capnogram pattern].
AB  - We report a case of substantial rebreathing which occurred during the
      thoracoscopic bulla resection despite a normal FICO2 reading on capnogram. Early
      detection of inspiratory unidirectional valve malfunction as the cause of the
      rebreathing was only possible by careful observation of the capnogram pattern.
      During the course of one lung anesthesia, a rising end-tidal CO2 concentration
      (FETCO2) and a change in the pattern of the capnogram were observed. However, the
      lowest FICO2 value in the late phase of inspiration stayed below the alarm limit
      setting of rebreathing. For this reason, the capnograph failed to identify the
      beginning of inspiration and perceived the high FICO2 value in early inspiration
      as part of expiratory plateau. In case of the inspiratory valve malfunction, it
      is possible that analysis of the capnogram reveals underestimated FICO2.

PMID- 8538015
TI  - [Evaluation of 26G pencil point spinal needle in combined epidural-spinal
      anesthesia].
AB  - Twenty six gauge pencil point spinal needles and an adaptor for the fixation of
      the spinal needle were developed for combined epidural/spinal anesthesia on an
      experimental basis and applied on 110 patients. The length of the spinal needles
      was either 11.7 cm or 13 cm. Fifty out of 110 patients were punctured with the
      11.7 cm needle and then were divided into 2 groups. The difference in length of
      the spinal and epidural needles was 8 mm in group 1 and 15 mm in group 2. In 80%
      of the patients in group 1 and in 95% of the patients in group 2, the
      subarachnoidal space was reached on the first puncture. These results indicate
      that the subarachnoidal space can be more easily punctured when a spinal needle
      15 mm longer than the epidural needle is used. On the other hand, when a 13 cm
      spinal needle was employed, it often did not remain in place during drug
      injection. This problem could be solved, however, by using an adaptor with which
      the spinal needle was fixed firmly on the epidural needle at the point of dural
      puncture. The incidence of the post dural puncture headache was 1.7% (1 out of 60
      patients).

PMID- 8538016
TI  - [The clinical scoring system for predicting the risk of intraoperative and
      postoperative bronchospasm].
AB  - Patients with bronchial asthma (BA) are usually considered to have a high risk of
      developing bronchospasm (BS) during anesthesia. Our clinical scoring system for
      preoperative assessment in BA patients was used to predict the risk of
      intraoperative and postoperative BS. Thirty two patients with a history of BA
      were studied retrospectively, assessing preoperatively with our clinical scoring
      system; Bronchial Asthma Risk Index Score (BARIS). BARIS was composed of a total
      of ten items. Five of them were scored before inhalation of bronchodilators and
      remaining five items were scored after the inhalation. Each item was scored by 0,
      1, or 2. Four of 32 patients developed BS peroperatively (BS group). Twenty eight
      patients developed no BS peroperatively (control group). The total scores of pre
      inhalation five items were 4.8 +/- 1.9 in BS group and 2.0 +/- 1.3 in control
      group, and the total scores of post-inhalation five items were 4.0 +/- 1.4 in BS
      group and 1.3 +/- 1.0 in control group. There were significant differences
      between the two groups (P < 0.05, Mann-Whitney U-test). We conclude that BARIS is
      useful in evaluating the risk of peroperative bronchospasm in patients with a
      history of bronchial asthma.

PMID- 8538017
TI  - [Inherited cancer--concept and classification].
AB  - Hereditary cancer syndrome and some recessibly inherited diseases with increased
      predisposition to cancer are reviewed with special reference to their recent
      concept and classification. That tumor suppressor genes and some oncogenes are of
      potential relevance to their development is discussed.

PMID- 8538018
TI  - [Mechanisms of hereditary tumorigenesis].
AB  - Hereditary cancers have been shown to develop through at least two mechanisms.
      Development of retinoblastoma and Wilms' tumor is usually not accompanied by
      other hereditary symptoms. Although they are inherited autosomal dominantly, gene
      mutations in recessive tumor suppressor genes were found to be responsible for
      these tumors. The other mechanism is the enhanced mutation in the cancer-prone
      hereditary diseases, such as xeroderma pigmentosum, Bloom's syndrome, etc. In
      xeroderma pigmentosum, for example, defects in DNA repair has been shown to
      enhance the frequency of mutation in the oncogenes and tumor suppressor genes.
      Recently, another repair-related mechanism, involving the mismatch repair, was
      found to be involved in the hereditary nonpolyposis colon cancer.

PMID- 8538019
TI  - [Linkage analysis of hereditary cancer syndrome].
AB  - Linkage analysis using polymorphic DNA markers have played significant roles in
      identification of genes related to development of cancer. The genes associated
      with hereditary cancer syndromes are divided into three classes, oncogenes, tumor
      suppressor genes, and genes related to the DNA repair system. The majority of
      these genes have been isolated through the mapping of the disease loci by linkage
      analysis of a large number of affected kindreds. I summarize here the principle
      of linkage analysis as well as a history of polymorphic DNA markers, RFLP
      (restriction fragment length polymorphism), VNTR (variable number of tandem
      repeat), and microsatellite markers.

PMID- 8538020
TI  - [Studies on tumor suppressor genes by gene/chromosome transfer].
AB  - The gene/chromosome transfer into cultured cancer cells has not only confirmed
      that genes isolated by the positional cloning method can actually suppress
      various transformed phenotypes of the cells, but also allowed to speculate
      cellular functions of cloned or uncloned tumor suppressor genes. One of the
      important functions of uncloned ones is to induce the cellular senescence program
      in immortal cancer cells, as revealed by the chromosome transfer. This method has
      also identified novel chromosomes (or chromosomal regions) carrying putative
      tumor suppressor genes, which have never been suggested by other approaches,
      e.g., LOH analyses. Thus, the studies on tumor suppressor genes using cultured
      cancer cells have different advantages from those of the molecular
      genetics/molecular biology studies.

PMID- 8538021
TI  - [Structure and function of tumor suppressor genes].
AB  - Tumor suppressor genes encode molecules involved in cell adhesion, cytoplasmic
      signal transduction, transcriptional regulation and DNA repair. Recent studies
      have shown that p53 and WT1 regulate the cell cycle by altering the expression of
      genes involved in controlling the activity of cyclin/CDK complexes. By contrast,
      RB regulates the expression of genes that mediate cell cycle progression from the
      G1 to S phase and its activity is negatively regulated by cyclin/CDK. Recent
      progress in this field is summarized in the light of cell cycle control.

PMID- 8538022
TI  - [Mechanisms for inactivation of tumor suppressor genes].
AB  - Tumor suppressor genes are inactivated by various mechanisms. Since a mutant
      allele of a tumor suppressor gene is recessive for cellular malignant
      transformation, mutation is heritable and germ line mutations of tumor suppressor
      genes such as retinoblastoma gene and p53 gene are well characterized. In the
      process of loss-of-function of a tumor suppressor gene, chromosome type of
      mutations are often involved, which results in tumor specific loss of
      heterozygosity (LOH) on a specific chromosome. Somatic mutations of the p53 gene
      in a variety of tumors were extensively studied and a huge data base is now
      available. Mutation spectra of the p53 gene in various tumors are different each
      other and to be used as a molecular indicator of carcinogens involved in each
      type of tumor.

PMID- 8538023
TI  - [Strategies for the detection and the identification of tumor suppressor genes].
AB  - The methods for the detection and the identification of tumor suppressor genes
      are characterized and classified as follows: Firstly; by the comparison of
      expressed genes or proteins between tumor cells and normal cells. Secondly; by
      the gene transfer. Thirdly; by the identification of proteins which are involved
      in the biochemical process for cell growth suppression and DNA repair. Human
      genome contains dozens of tumor suppressor genes and tumor suppression-related
      genes which have not yet been cloned. Positional cloning is the most reliable
      method for the cloning of these genes. However, it cost huge amount of labor and
      time. New methods developed in recent years, such as differential mRNA display or
      two hybrids system, would facilitate the identification and the molecular cloning
      of novel tumor suppressor genes.

PMID- 8538024
TI  - [Hemangioblastoma and von Hippel-Lindau disease].
AB  - Intracranial hemangioblastoma (Lindau's disease) is vascular-rich benign
      neoplasm, arise from vascular endothelium. They account for about 2-3% of all
      intracranial tumors. Its most common location is adult posterior fossa. Except
      for the cerebellum, they were sometimes found in the brainstem or spinal region.
      Common macroscopical findings is mural nodule with cyst in the cerebellum.
      Contrary, solid form is common in spinal and brainstem region. The lesions are
      readily identified by image diagnostic procedures. Intracranial hemangioblastoma
      associated with retinal hemangioblastoma is called "von Hippel-Lindau's disease",
      hereditary disease of autosomal dominant form with chromosome abnormalities of
      3p25-26. In other particular type of "von Hippel-Lindau's disease", intracranial
      hemangioblastomas are associated with renal cell carcinoma, pancreatic cyst or
      pheochromocytoma sometimes without retinal hemangioblastoma. Surgical extripation
      is the best choice of treatment for this disease. However, brainstem or spinal
      hemangioblastomas are sometimes difficult to remove totally.

PMID- 8538025
TI  - [Malignant glioma].
AB  - Recent advances in molecular genetics have disclosed oncogenes playing a
      significant role in the development of malignant gliomas. Amplification of the c
      erb gene which code EGFR and aberration of P53 oncogene play a significant role
      in the development of most malignant gliomas. Karyotype analysis of malignant
      gliomas revealed gains of chromosome 7, loss of chromosome 10, double minutes and
      loss of heterozygosity. The development of the tumors appear to result from the
      accumulation of those multiple genetic alterations. Although many cases of
      familiar malignant gliomas have been reported the role of hereditary factors in
      familial transmission still remains controversial. Chromosomal abnormalities
      seemed to be confined to the tumor cell, and no alteration in karyotype of
      peripheral blood, which indicated germ line mutation, was demonstrated. However,
      several authors indicated that the frequency of malignant gliomas in the
      relatives of patients was estimated more than ten times to the controls. Some
      hereditary factors might play a role in malignant gliomas.

PMID- 8538026
TI  - [Familial neuroblastoma].
AB  - Neuroblastoma (NB) is a common malignant solid tumor in childhood, accounting for
      about 40% of the solid children's neoplasms on the Japanese registry in 1993. It
      is known that some cases of NB are hereditary, but their incidence is very low.
      We report two patients with adrenal familial NBs and review the literature on
      familial NB. Two hit theory was proposed to explain the occurrence of hereditary
      and non-hereditary NBs. This theory supports the fact that the median age at
      diagnosis is much younger and the incidence of multiple primaries is higher in
      the familial NB than in non-familial cases. As therapy for NB improves and more
      children survive to adulthood, there will be more opportunity to study their
      offspring.

PMID- 8538027
TI  - [von Recklinghausen's disease and its pathogenesis].
AB  - von Recklinghausen's disease was first described in 1882. Formerly, it was
      considered a single disease, but is now known to be two distinct disease,
      neurofibromatosis 1 (NF 1, peripheral form of neurofibromatosis) and
      neurofibromatosis 2 (NF 2, bilateral acoustic neurofibromatosis).
      Neurofibromatosis is inherited as an autosomal dominant with a high rate of
      penetrance. NF 1 gene is located in the pericentromeric region of chromosome 17.
      NF 2 gene is localized to chromosome 22. Clinically, there are some
      characteristic signs and symptoms. The typical NF 1 patient has cafe-au-lait
      spots, melanin pigmentation and palpable neurofibromas, while NF 2 has its onset
      with the development of tinnitus or hearing loss, due to the presence of
      bilateral acoustic neuroma.

PMID- 8538028
TI  - [Familial pituitary tumors].
AB  - Familial pituitary tumors are relatively rare. Most commonly, they occur as a
      part of multiple endocrine neoplasia type 1 (MEN 1). However, familial pituitary
      adenomas unrelated MEN 1 (familial pituitary adenomas) are extremely rare. In
      review of MEN 1 in Japan, 60% of the patients with MEN 1 had pituitary tumors.
      Only 45 cases of familial pituitary adenomas have been reported from 20 families.
      In our review of familial pituitary adenomas, 30 (67%) of 45 reported cases are
      acromegaly or gigantism. This incidence is much higher than 28% in MEN 1 patients
      with pituitary tumors. Allelic deletions at 11q13 were identified in MEN 1
      associated pituitary adenomas and familial pituitary adenomas in two gigantism
      brothers.

PMID- 8538029
TI  - [Familial occurrence of thyroid tumors].
AB  - In 1986, familial medullary thyroid carcinoma (FMTC) was recognized clinically as
      a distinct entity, clearly distinguished from multiple endocrine neoplasia (MEN),
      being characterized by the development of MTC in the absence of any additional
      neoplasms. Ret proto-oncogene was first identified in 1985 using transformation
      assay. The gene was mapped to the chromosome 10, similar to MEN and FMTC, and was
      expressed at high levels in MTC. In 1993, ret mutations were identified in
      patients with MEN2A and FMTC, and many other mutations has been clarified up to
      today. What is the normal function of RET and how ret mutations lead to tumor
      formation in MEN and FMTC are focus of intensive studies at present.

PMID- 8538030
TI  - [Multiple endocrine neoplasia type I].
AB  - Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined
      occurrence of primary hyperparathyroidism, pancreatic endocrine tumors, and
      neoplasms of the anterior pituitary gland. The disease is inherited as an
      autosomal dominant disorder with a high penetrance. Although many investigators
      have localized the causative genes to chromosome 11q3 by linkage analysis, the
      MEN1 gene remains unidentified. The use of molecular genetic markers in family
      linkage studies, however, have made it possible to identify gene carriers.
      Repetitive screening combined with the assignment of gene-carrier status will
      provide possibilities for therapeutic or prophylactic intervention earlier in the
      development of each of the manifestations of this syndrome, such as
      gastrointestinal bleeding secondary to ulcers or malignant transformation.

PMID- 8538031
TI  - [Multiple endocrine neoplasia type 2A, type 2B and familial medullary thyroid
      carcinoma syndrome].
AB  - Recently, germline mutations in the RET proto-oncogene were found to be
      associated with multiple endocrine neoplasia (MEN) syndromes, MEN 2A, MEN 2B and
      Familial medullary thyroid carcinoma (FMTC). In patients with MEN 2A and FMTC
      different point mutations have been identified in exons 10 and 11 of the cysteine
      rich regions of RET. Patients with MEN 2B have a single point mutation (ATG to
      ACG) at codon 918 of RET. Therefore, a direct DNA testing has been developed to
      provide a highly accurate technique of detecting kindred members who have
      inherited a specific mutation associated with MEN 2A, MEN 2B or FMTC. In USA and
      Europe, prophylactic thyroidectomy has been performed on the basis of positive
      DNA testing, and the presence of a C-cell hyperplasia or a small medullary
      thyroid carcinoma was confirmed in each patient operated. Through nationwide
      survey in Japan, 233 patients with MEN 2 syndrome have been identified. They
      consisted of 180 MEN 2A, 18 MEN 2B, 13 FMTC and 22 unclassified patients. At
      follow-up, 47% of patients had recurrent medullary thyroid carcinoma and 5.7% of
      patients died of the disease. Genetic analysis was performed on 15 patients of 6
      unrelated families in our series, and the results revealed that germinal
      mutations of RET as previously reported were also responsible for MEN 2 syndrome
      in Japanese. DNA analysis and prophylactic thyroidectomy for kindred members at
      risk for MEN 2 are likely to be beneficial in Japan as well.

PMID- 8538032
TI  - [Cancer family syndrome in lung cancer--Li-Fraumeni syndrome in lung cancer].
AB  - A family with lung cancer family syndrome was reported with 5 persons of the Ist
      relatives, 3 of IInd relatives and one of IIIrd relatives, in whom one was
      synchronous, one asynchronous double cancers and one was in combination with lung
      cancer and renal cell carcinoma. Four surgical specimens were investigated in
      terms of p53 mutation by PCR-SSCR and also the analysis of ploidy pattern, AgNOR
      and PCNA. As a result, a special pattern of lung cancer family syndrome was not
      detected as compared with other lung cancer patients.

PMID- 8538033
TI  - [Familial polyposis coli].
AB  - Familial polyposis coli (FAP) presents multiple adenomas in the large bowel.
      Also, polyps in the upper gastrointestinal tract are observed in some cases of
      FAP. Since the risk of developing colorectal cancer is almost 100% in FAP,
      patients need surgical treatment (colectomy) after a diagnosis of FAP is made.
      After a gene for FAP (APC gene) was identified, an accurate diagnosis of FAP is
      becoming possible by examining APC gene, even though patients show no clinical
      manifestations. Many studies revealed various mutations of APC gene and examined
      the relation between the site of the germline APC mutation and the phenotypic
      expression of FAP. These studies suggested that there was a Genotype-Phenotype
      Correlation in FAP. Some differences of clinical features in FAP, such as profuse
      type and attenuated type of FAP (AAPC), are now considered to be caused by the
      difference of the site of the germline APC mutation.

PMID- 8538034
TI  - [Hamartomatous polyposis syndrome].
AB  - The hamartomatous polyposis syndromes, which comprise Peutz-Jeghers syndrome,
      juvenile polyposis, and Cowden's disease, occur less frequently. These disorders
      are characterized by multiple hamartomatous polyps in the gastrointestinal tract,
      and distinctive extraintestinal manifestations. We have recognized that these
      have inheritance with autosomal dominant trait by genetic studies. Most of them
      have high malignant potential which make transformation to neoplasms in
      gastrointestinal tract and extraintestinal organs. It is necessary for patients
      with these disorders to manage appropriately. Therefore, we must understand their
      natural histories and pathological characterization. Because affected patients
      and their first degree relatives belong to high risk groups of malignant
      neoplasms, we have to intensively survey them through their lifetime.

PMID- 8538035
TI  - [Hereditary solitary adenoma].
AB  - Hereditary solitary adenomas is characterized by a low number of adenomatous
      polyps (usually fewer than 100), but still carries an elevated risk of colon
      cancer. This colon cancer susceptibility disorder is believed to be inherited as
      an autosomal dominant. Recent molecular studies have revealed that the mutant
      alleles responsible for this disorder is mapped to the adenomatous polyposis coli
      (APC) locus on human chromosome 5q. The average age at onset for developing
      cancer is approximately 15 years later than that observed in classical APC and
      approximately 10 years earlier than patients with sporadic colorectal cancer.

PMID- 8538036
TI  - [Hereditary hematopoietic malignancy with emphasis of juvenile chronic
      myelogenous leukemia and 7 monosomy syndrome].
AB  - Children with type 1 neurofibromatosis (NF-1) are at increased risk of
      myeloproliferative disorders (MPD). NF-1 gene was supposed to be a tumor
      suppressor gene. The majority of MPD patients in children with familial NF-1
      inherited the disease from their mother. Loss of heterozygosity (LOH) of NF-1
      gene has been reported in juvenile chronic myelogenous leukemia (JCML) and 7
      monosomy syndrome (7MS) patients with NF-1. On the contrary, no LOH of NF-1 gene
      was found in these patients without NF-1. NF-1 gene is considered to be involved
      in the pathogenesis of JCML and 7MS with familiar NF-1. Other familiar
      hematopoietic malignancy, such as Fanconi's anemia, Down's syndrome and Li
      Fraumeni syndrome are also discussed.

PMID- 8538037
TI  - [Hereditary renal tumors: Wilms' tumor--congenital anomalies' syndrome].
AB  - The genetics and associated abnormalities of Wilms' tumor are reviewed. Wilms'
      tumor is associated with several congenital syndromes such as WAGR (Wilms' tumor,
      aniridia, genitourinary malformation, mental retardation) syndrome, Denys-Drash
      syndrome, Beckwith-Wiedemann syndrome, etc. However, the association with such
      syndromes is relatively infrequent and accounts for less than 5% of all clinical
      patients with Wilms' tumor. WAGR syndrome and Denys-Drash syndrome are associated
      with loss of WT1 gene located in the chromosome 11p13, and BW syndrome is
      considered to be due to duplication of the paternal 11p15 allele (WT2). The
      association of Wilms' tumor with primary brain tumors in a daughter and a mother
      is also described.

PMID- 8538039
TI  - [Familial malignant melanoma].
AB  - Approximately 8 to 12% of cases of malignant melanoma (MM) are estimated to be
      familial in foreign countries, but such familial MM (FMM) is rare in Japan.
      Eleven Japanese cases of FMM, including our 3 cases in a family, have been
      reported. Comparison studies have revealed that the mean age at the onset of FMM
      is younger than that of sporadic MM. However, it is difficult to exclude the
      effects of early recognition of MM by frequent examinations in FMM families. In
      the majority of the families, the propensity to MM is associated with the
      presence of atypical mole, so-called dysplastic nevus syndrome phenotype. The
      inheritance pattern for FMM is thought to be autosomal dominant with incomplete
      penetrance. Linkage studies have shown at least two FMM loci on chromosome 1p36
      and 9p21, thus providing a support for genetic heterogeneity in FMM.

PMID- 8538038
TI  - [Familial bladder cancer].
AB  - Despite little evidence for a hereditary cause of most cases of bladder cancer,
      two different patterns of genetic involvement have been suggested: an autosomal
      dominant pattern that accounts for a very small number of cases and a
      multifactorial, polygenic pattern involving genetic and environmental
      interaction. Inherited homozygous defect of the glutathione S-transferase M1 gene
      is a good example of the latter pattern. Molecular genetic analysis has revealed
      two distinct molecular pathways to bladder tumorigenesis. Papillary noninvasive
      tumors as well as invasive disease harbor the chromosome 9 allelic loss, while
      carcinoma in situ contains a p53 gene mutation without an alteration of
      chromosome 9. The p53 gene mutations are closely associated with high grade, high
      stage urothelial cancers and immunohistochemical detection of the p53 protein
      alterations may be promising prognostic marker. Analysis of the p53 gene mutation
      pattern suggested a monoclonal origin for multicentric occurrence of urothelial
      cancers.

PMID- 8538040
TI  - [Multiple perifollicular fibroma].
AB  - Perifollicular fibroma (PF) is a cutaneous hamartomatous proliferation of the
      pilar connective tissue sheath. It occurs predominantly on the face or neck in a
      solitary or multiple form. Histologically, it is characterized by a concentric
      arrangement of collagen fibers surrounding hair follicles. Other related
      proliferations include fibrofolliculoma and trichodiscoma, which are often
      complicated or have histological overlapping features, so they may represent the
      same spectrum of pilar mesodermal proliferation. Some individuals with multiple
      PFs have colonic polyposis, some of which develop into carcinomas, and there are
      suggestions of autosomal dominant inheritance. It appears that patients with
      multiple PFs and/or other connective tissue hamartomas may be at risk for colonic
      polyposis. Cutaneous signs may lead to an early discovery of digestive diseases.

PMID- 8538041
TI  - [Familial breast cancer].
AB  - Japanese breast cancer families were collected and classified into the following
      7 types according to the onset age and the distribution of other cancers in the
      family lines; early-onset type, late-onset type, familial breast-ovarian cancer
      type, familial breast-prostate cancer type, familial breast-thyroid cancer type,
      familial male and female breast cancer type and multiple primary cancer type. We
      have detected no p53 germ line mutations in the patients from these families.
      Linkage with BRCA1 was not detected in any single families. These data indicate
      that neither BRCA1 or p53 is a major susceptible gene in Japanese familial breast
      cancer. However, in the two site-specific breast cancer families, the same
      nonsense mutation of the BRCA1 gene was detected.

PMID- 8538042
TI  - [Familial ovarian cancer, uterine cancer].
AB  - Familial ovarian cancer is described as a familial aggregation of ovarian cancer.
      The disease is heterogeneous, with at least three genotypes prodisposing to
      distinctive hereditary syndrome, site-specific ovarian cancer, wherein familial
      cancer risk is restricted to ovarian carcinoma; breast/ovary carcinoma syndrome,
      that is ovarian carcinoma in association with carcinoma of the breast; and Lynch
      syndrome II, characterized by hereditary nonpolyposis colorectal cancer with
      proximal colonic cancer predominance, endometrial carcinoma, and ovarian
      carcinoma. When a familial aggregation of ovarian cancer is observed, unaffected
      women in the family should have periodic gynecologic examinations, including
      cytologic and ultrasonographic, radiologic studies and magnetic resonance
      imaging, in an effort to detect preinvasive ovarian cancer. Until more reliable
      diagnostic methods are developed, however, the physician should consider the
      advisability of prophylactic oophorectomy and oral contraceptives when counseling
      women who have several close relatives with ovarian cancer.

PMID- 8538043
TI  - [Genetics of retinoblastoma].
AB  - Recent advancement of molecular genetics has enabled us to perform presymptomatic
      prediction for hereditary retinoblastoma, based on RB gene diagnosis. We used PCR
      combined with SSCP and heteroduplex analysis to screen leukocyte DNA, exon by
      exon, in patients with bilateral retinoblastoma. Germline mutations were detected
      in the 22 of the 33 cases, and, in 16 cases, the mutations were identified by
      sequencing. Among 2 families with those hereditary retinoblastoma presymptomatic
      prediction by the method described above was applied for 2 newborn babies,
      resulting in both success. It is expected that gene diagnosis will be applied for
      not only bilateral but also unilateral cases for genetic counseling.

PMID- 8538044
TI  - [Familial sacrococcygeal teratoma].
AB  - Familial sacrococcygeal teratomas are very rare. Up to now, only 8 kindreds (31
      patients, including 1 Japanese kindreds) have been reported. All cases are Altman
      type IV variety. The tumor complex consists of a presacral teratoma and
      sacrococcygeal bony anomalies. The most common symptoms are constipation and
      anorectal stenosis. Two patients died. One died of meningitis following removal
      of a large benign tumor because of communication with a spinal arachinoid space.
      The other, with a large benign tumor, died as a result of malignant change, 10
      years later after the first operation. The incidence of malignant change of
      familiar sacrococcygeal teratoma is rare in comparison with that of non-familiar
      sacrococcygeal teratomas.

PMID- 8538045
TI  - [Hereditary gingival fibromatosis].
AB  - Fibromatosis may be defined as diffuse poorly circumscribed overgrowth of the
      fibrous tissue that infiltrates adjacent normal tissues. They are difficult to
      eradicate surgically, and recur but not metastasize. Gingival fibromatosis is
      generally regarded as a disease that leads to an extensively diffuse and
      remarkable hyperplasia of the maxillo-mandibular gingiva. Occasionally, this
      lesion covers all teeth. The histogenesis of the fibromatosis remains
      unexplained. Trauma, endocrine, idiopathic factors and genetic factors have been
      implicated, but it is uncertain whether any of then play a major role in the
      development of the disease. Occasional cases with familial history have been
      reported. The treatment of choice would appear to been block resection of the
      tumor and surrounding normal structures. Although, this lesion has a high
      recurrent rate. For this reason, in many of the case reports, that it has been
      recommended that the follow up period is considerably less than three years.

PMID- 8538046
TI  - [Hereditary non-polyposis colorectal cancer (HNPCC)].

PMID- 8538047
TI  - [Li-Fraumeni syndrome].
AB  - The Li-Fraumeni syndrome was initially recognized through clinical observations
      at the bed side, which was followed by epidemiological studies. Children
      suffering from rhabdomyosarcoma were shown to have two or more of six forms of
      cancer in their parents, grandparents and other relatives, indicating cancer
      family syndrome. This syndrome has been shown to involve tumor suppressor gene
      p53 mutations in the germ-line. The patients in the family most often have a
      proband with soft tissue sarcoma or osteosarcoma, and relatives with breast
      cancer, brain tumor, leukemia and adrenocortical cancer. Members of the family
      also appear to be at risk for developing second independent malignancies during
      their life span. Recommendations on predictive testing for germ line p53
      mutations among cancer-prone individuals have been made by the subcommittees,
      which were sponsored by National Cancer Institute and the National Center for
      Human Genome Research.

PMID- 8538048
TI  - [Muir-Torre syndrome].
AB  - Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis that is
      characterized by the presence of at least one sebaceous gland tumor with or
      without keratoacanthoma, and a minimum of one internal malignancy. The most
      commonly associated neoplasms were colorectal (51%) and genitourinary (25%). MTS
      shares a number of clinical and pathological presentations with hereditary
      nonpolyposis colorectal carcinoma (HNPCC), including: tendency to develop right
      sided colon cancers; predisposition for the development of extracolonic tumors;
      and prolonged survival after surgical treatment. These family members should be
      monitored to detect cancers preliminaly and enrolled in life-long surveillance.

PMID- 8538049
TI  - [Chromosome breakage syndrome and fragile X syndrome].
AB  - Chromosome instability is a characteristic cytogenetic feature of a number of
      genetically determined human disorders collectively known as chromosome breakage
      syndromes. Included among the disorders are Bloom's syndrome (BS), Fanconi's
      anemia (FA), ataxia telangiectasia (AT). In each of the syndromes chromosome
      instability exists in the form of increased frequencies of breaks and
      interchanges occurring either spontaneously or following treatment with various
      DNA-damaging agents. These diseases have in common an autosomal recessive
      transmission and an increased tendency to develop malignancies. The blood cells
      of subjects with AT, BS, or FA are significantly more radiosensitive than those
      of controls, particularly in the occurrence of chromosome aberrations.

PMID- 8538050
TI  - [Xeroderma pigmentosum].
AB  - Xeroderma pigmentosum (XP), an autosomal recessive disorder, is characterized by
      extreme sensitivity to sun exposure, a high incidence of skin cancer and frequent
      neurological abnormalities. Cells from XP patients of seven complementation
      groups (A-G) have defects in the nucleotide excision repair of UV damage, whereas
      the defect of another type, the XP variant, is not yet known. Recent discoveries
      of causative genes of XP have uncovered the molecular mechanisms of nucleotide
      excision repair. The analysis of gene mutation in XPA gene made a diagnosis of
      patients and carriers quicker and easier. Further, a relationship between the
      type of XPA gene mutation and clinical severity has also been uncovered. By
      analysing skin cancers developed on XP patients, the representative of UV-induced
      skin cancers, the molecular bases of UV skin carcinogenesis have also been
      rapidly discovered.

PMID- 8538051
TI  - [Primary immunodeficiency diseases].
AB  - A substantial proportion of patients with primary immunodeficiency diseases
      develop tumors, particularly those of lymphoreticular system caused by Epstein
      Barr virus (EBV). Primary immunodeficiency renders patients susceptible to EBV by
      reducing immune reactions and surveillance abilities against the virus or
      inducing overreaction of the responding cells to the antigens. Recent progress in
      molecular biology has unraveled the genes responsible for several types of
      primary immunodeficiency diseases. The cloning of the ATM gene demonstrated that
      the mutations in this gene were observed in the members of all the families
      affected with ataxia telangiectasia (AT), indicating the crucial role of this
      gene in the pathogenesis of AT. The protein encoded by the ATM gene shows a high
      sequence homology with several proteins which are presumed to be involved in the
      regulation of the cell cycle transition. Accumulating evidence indicates that AT
      derived cells are sensitive to irradiation due to the abnormalities in p53
      dependent cell cycle arrest at G1 phase. Thus, the ATM product may regulate the
      cell cycle at G1 phase in a p53-dependent manner and the defect of the gene may
      lead to the accumulation of cells with DNA damages, thereby causing malignant
      transformation.

PMID- 8538052
TI  - [Negative repressor THZif-1 of protooncogene c-myc].
AB  - A human recombinant cDNA clone that encoded 253 amino acids residues of a zinc
      finger protein (THZif-1) was cloned by screening a cDNA library prepared from
      human promyelocytic leukemia HL60 cells with synthetic oligodeoxynucleotide
      probes that corresponded to the amino acid sequences of tryptic peptides derived
      from the DNA-binding protein specific for the nuclease-hypersensitive element
      (NHE) of the human c-myc gene. The predicted amino acid sequence of THZif-1
      included a DNA-binding domain that contained five tandemly repeated zinc finger
      motifs. The three amino-terminal sets of zinc finger motifs, including the second
      finger, were found to be responsible for high-affinity interactions with the
      triple-helical conformation of NHE, as well as for high-affinity binding to the
      single-pyrimidine-rich strand of NHE in a sequence-specific manner.
      Cotransfection, trans-activation and in vitro transcription studies using the
      wild-type form and THZif-1 with a mutated second zinc finger motif demonstrated
      that the DNA-binding activity specific for H-form DNA of NHE was a prerequisite
      for the negative regulation of the expression of the c-myc gene.

PMID- 8538053
TI  - [Gene structure and transformation mechanism of HTLV-I].
AB  - HTLV-I is the etiological agent of the adult T cell leukemia. HTLV-I genome
      contains the novel pX region in addition to the genes common to all retroviruses.
      Tax, encoded at the pX region, may play a central role in cellular
      transformation, however, little information is available on the mechanism. Tax
      transactivates transcription through three different pathways, namely, CRE, kB
      motif and CArG box mediated pathways. In ras cooperative focus formation in REF,
      transcriptional activation through the CArG box seems to play an important role,
      although transcription through the CRE pathway plays a central role in tax
      mediated transformation of Rat-2 cells. These results suggest that the mechanism
      of transformation by tax varies with the cell type and/or the property of
      transformation.

PMID- 8538054
TI  - [The function and role of extrathymic T cells].
AB  - Murine liver contains alpha beta T cells with intermediate TCR (TCRint) as well
      as alpha beta T cells with bright TCR. Liver TCRint cells express NK1.1 Ag (NK1+
      TCRint) and IL-2 receptor beta chain, both of which are NK cell markers and are
      not expressed on conventional T cells. Liver NK1+ TCRint cells consist of CD4-8-
      double negative T cells and CD4+ T cells and have V beta 8+ T cell preponderance.
      They are dependent on class Ib or CD1 molecules of APC for their development.
      They can also develop thymus independent manner, because athymic nude mice have
      this population. These NK1+ TCRint cells in the livers of both euthymic and
      athymic mice were found to be activated by systemic administration of IL-12 and
      increased NK1 expression (NK1high TCRint) and cytotoxicity against various NK
      sensitive and resistant tumors. Cytotoxicity assays after treatment of IL-12
      stimulated hepatic MNC with respective Abs and C revealed that CD4+ NK1high
      TCRint cells are responsible for IL-12 induced cytotoxicity. Although NK1+ TCRint
      cells were normally few in the lungs, a significant proportion of NK1high TCRint
      cells with strong cytotoxicity was also induced in the lung by IL-12.
      Interestingly, adoptive transfer of IL-12 stimulated hepatic MNC into other mice,
      which were pre-injected with tumors, inhibits hepatic metastases of EL4 cells and
      pulmonary metastases of 3LL cells as similarly as IL-12 administration. Transfer
      experiments after treatment of IL-12 stimulated hepatic MNC with respective Ab
      and C revealed that depletion of either NK1+ cells, CD3+ cells or CD4+ cells but
      not CD8+ cells greatly impaired antimetastatic effect in both organs. Thus, CD4+
      NK1high TCRint cells are a major antimetastatic population, especially, against
      hematogenous metastases.

PMID- 8538055
TI  - [Human papillomavirus type 16-gene functions relevant to molecular human
      carcinogenesis].
AB  - Human papillomavirus type 16 is a strong ethiologic agent of tumor development in
      human mucous epithelia such as uterine cervix. The virus two early genes, E6 and
      E7, have been characterized to be oncogenes that transform various cells and cell
      lines in vitro. Extensive analyses of E6 and E7 proteins revealed that these two
      oncoproteins interacted with cellular tumor suppressors, p53 and pRb,
      respectively. Thus, oncogenic potentials of the E6/E7-genes could be explained in
      part by the consequence of crosstalk of E6/E7-proteins and the cell cycle
      regulators. Furthermore, telomerase activation that protects telomere erosion
      appeared to by necessary for HPV16-oncogenesis and was demonstrated in HPV16
      immortalized human epithelial cell lines. This line of evidence now enabled us to
      describe, but not fully, a scheme of an earlier process of human carcinogenesis
      induced by this virus type.

PMID- 8538056
TI  - [Early diagnosis of pancreatic carcinoma and utility of helical CT].
AB  - The pancreatic carcinoma, what is one of difficult carcinomas to treat. It is
      because the pancreatic carcinoma does infiltrate to external at early stage.
      However, it leads to increase of operation with significance to check it at early
      stage. Helical CT is developed in late years, and spread rapidly. This
      examination includes many clinical utilities. In early diagnosis of pancreatic
      carcinoma, improve former problems, and is thought that utility is high.

PMID- 8538057
TI  - [Characteristics of medical institutions visited by patients with 26 intractable
      diseases who are residents of Saitama Prefecture (comparison of the data for 1984
      and 1988)].
AB  - To obtain basic data concerning the availability of medical care for intractable
      diseases in a large city and its environs, we analyzed the data of Saitama
      Prefecture. These data were selected from a nationwide survey conducted by the
      Epidemiology of Intractable Diseases Research Committee of the Ministry of Health
      and Welfare in Japan. The characteristics of medical institutions visited by
      patients with 26 intractable diseases were analyzed. The patients were receiving
      financial aid for treatment. The subjects were 4234 patients in 1984 and 6804
      patients in 1988. In addition, we compared the data of 1984 with those of 1988.
      The results are as follows: 1) In both years, the characteristics of medical
      institutions which were visited varied in terms of the individual disease. The
      proportion of patients who visited medical institutions in the same medical
      service area and in the same prefecture were both very low. The percentage of
      patients who visited medical institutions in Tokyo was more than 30% of the
      total, and was more than 50% for the disease with the highest proportion of
      patients. The dependency on Tokyo for medical institutions was inversely
      proportional to the distance from Tokyo. Most patients were highly dependent on a
      large hospital, but the proportion of patients with SMON and ulcerative colitis
      who visited a large hospital was markedly lower than that for other diseases. 2)
      A comparison of the data of 1984 with those of 1988 showed that in most of
      medical service areas, the proportion of patients who visited medical
      institutions in the same medical service area and in Saitama Prefecture
      increased, but in Tokyo Prefecture the proportion decreased. We continuously
      observed a high dependency on a university hospital located about 60km distance
      from downtown Tokyo, but the dependency slightly decreased in 1988. When a new
      branch of a university hospital opened, many intractable disease patients then
      depended on that branch. These results suggest that the self-sufficiency levels
      of medical services for intractable diseases gradually rose in Saitama
      Prefecture. The illness behavior of intractable disease patients in Saitama
      Prefecture did not show any remarkable changes, therefore those results in
      Saitama Prefecture might indicate a universal characteristic of medical
      institutions visited by intractable disease patients who live in the envirous of
      a large city (Tokyo).

PMID- 8538058
TI  - [A study of preventive medicine in relation to mental health among middle
      management employees (Part 2)--effects of long working hours on lifestyles,
      perceived stress and working-life satisfaction among white-collar middle
      management employees].
AB  - Recently, we have introduced the holistic method into health care of workers and
      aimed at improvement of Quality of Life (QOL). It has been made clear that
      primary prevention of diseases needs lifestyle appraisal. Therefore, we studied
      the daily working hours and the effects of long working hours on lifestyles,
      perceived stress and working-life satisfaction, which we used as a subjective
      index of Quality of Life (QOL), based on data obtained from a survey of 1,026
      department chiefs and 2,902 section chiefs in 110 large companies in Japan in
      1990. The results are summarized as follows. (1) The percentage of those working
      10 hours per day was 41.6% for department chiefs and 40.4% for section chiefs,
      and for 11 or more working hours it was 24.1% in department chiefs and 30.9% in
      section chiefs. The younger both department and section chiefs, the longer their
      working hours. (2) Both department and section chiefs had a significant
      relationship between long working hours and poor sleeping habits, poor physical
      exercise, feeling busy, irregularity of daily life and irregularity of daily
      meals. The department chiefs had a significant relationship between long working
      hours and unbalanced nutrition or no hobbies. The section chiefs had a
      significant relationship between long working hours and drinking many cups of tea
      or coffee, taking a lot of salt or ill physical condition during the past six
      months.

PMID- 8538059
TI  - [Reproductive histories of coastal and inland women with and without exposure to
      methylmercury in Kumamoto].
AB  - To examine the difference in abnormal conception by region and generation and its
      possible causes in the town of Tsunagi, which experienced intensive methylmercury
      pollution during the 1950s and 1960s, reproductive histories of 109 women in 3
      coastal villages and 64 controls in 5 inland villages were obtained by visit- and
      interview-study in 1991. There were about 290 married women in respective
      regions. The subjects were divided into 4 age groups to form 10-year-birth
      cohorts from 1915 to 1954. The rate of sterility and those who had never become
      pregnant after marriage, did not differ between coastal (7.3%) and inland women
      (6.3%). The younger the birth cohort, the smaller the total number of
      conceptions. The rate of abnormal conception, i.e., abnormal conception
      (abortion+stillbirth) per normal conceptions (total number of conceptions--number
      of artificial abortions), in the coastal women tended to increase after the 1960s
      with its peak (19%) in 1965-70. The rate in the inland women was already as high
      as 15% in 1945-50, and was constantly above 10% afterwards. However, it did not
      differ between the two groups during 1950-1970, when severe methylmercury
      pollution occurred in the area. Breakdown of the abnormal conceptions in the
      inland women showed 4 stillbirths and 19 abortions, among the latter of which 16
      were related to climbing up and down the hills to fetch water, hard agricultural
      work and agitation. The abnormal conceptions in the coastal women showed 3
      stillbirths and 19 abortions. Sixteen of the latter were not related to any
      specific physical causes.

PMID- 8538060
TI  - [Relation of serum fatty acids with serum lipids and blood pressure in women].
AB  - We studied the correlation of serum fatty acids, a potential coronary risk
      factor, with serum lipids and blood pressure. The subjects were women aged 40-69
      of four Japanese populations (fishing, coastal farming, inland farming and urban
      populations) and a Caucasian population in which different dietary habits have
      been reported. Within populations, the total cholesterol level was not correlated
      with serum fatty acids. HDL-cholesterol was inversely correlated with saturated
      fatty acids and monounsaturated fatty acids, and positively correlated with
      polyunsaturated fatty acids although not significantly so in all populations. LDL
      cholesterol was not correlated with saturated fatty acids and mono
      polyunsaturated fatty acids, but was positively correlated with polyunsaturated
      fatty acids. Triglyceride was positively correlated with saturated fatty acids
      and monounsaturated fatty acids, and inversely correlated with polyunsaturated
      fatty acids for all populations. Blood pressure correlated positively with
      saturated fatty acids, and inversely with polyunsaturated fatty acids although
      these associations were not statistically significant.

PMID- 8538061
TI  - [Effect of physical activity on physical fitness among workers].
AB  - We conducted a cross-sectional study to clarify the effects of physical activity
      on physical fitness. Physical fitness tests were offered to workers of companies
      manufacturing automobile parts from December, 1992 to December, 1993. The
      subjects were 1,217 male and 600 female workers who participated in the physical
      fitness test. From this group, we analyzed 1,048 male and 522 female workers who
      answered a physical activity questionnaire. The questionnaire included age, sex,
      working posture, physical activity during working time and physical activity
      during leisure time. The physical fitness tests were composed of grip strength,
      standing trunk flexion, foot balance with closed eyes, jumping reaction time and
      step tests. We classified the subjects into low performance group and high
      performance group for each test. In addition, we classified the subjects into
      different groups by age (16-29 years old, 30-49 years old old and 50-69 years
      old), by working posture (standing and sitting), as well as by activity levels
      during working time and leisure time physical activities (inactive and active).
      Thus, we examined potential risk factors for the physical fitness by a multiple
      logistic regression model. The results were as follows: 1. Standing work was a
      significant risk factor for grip strength, foot balance with closed eyes and
      jumping reaction time in male workers, and standing trunk flexion, foot balance
      with closed eyes, jumping reaction time and the step test in female workers. 2.
      Physical activity during working time was not related to physical fitness in male
      and female workers. 3. Inactivity during leisure time was a significant risk
      factor for standing trunk flexion, foot balance with closed eyes, jumping
      reaction time and the step test in male workers, and grip strength and foot
      balance with closed eyes in female workers. 4. Young age (16-29 years old) was a
      significant risk factor for grip strength, standing trunk flexion, foot balance
      with closed eyes, jumping reaction time and the step test in male and female
      workers. Middle age (30-49 years old) was a significant risk factor for foot
      balance with closed eyes and jumping reaction time in male workers, and standing
      trunk flexion, foot balance with closed eyes, jumping reaction time and the step
      test in female workers.

PMID- 8538062
TI  - [Salivary calcium and total protein in relation to dental caries].
AB  - To evaluate the relationship between salivary components (calcium: Ca, total
      protein: T-Pro) and dental caries, we collected nonstimulated and expectorated
      saliva from 131 primary school children aged 11 years old. All salivary samples
      were taken in the morning (11:00-11:30 A.M.) on Feb. 17, 1994, while the subjects
      were at rest. The salivary Ca concentration (mg/dliter), total salivary protein
      concentration (mg/mliter) and salivary flow rate (mliter/min) were measured based
      on the salivary sample taken for each person for 30 minutes at most. For each
      subject the Ca secretion rate (micrograms/min), T-Pro secretion rate
      (micrograms/min) and Ca/T-Pro ratio were determined. The numbers of permanent
      teeth erupted, and decayed, missing and filled (DMF) teeth for each subject were
      obtained from dental records. For the entire group we observed that the numbers
      of DMF teeth were highly correlated with the numbers of permanent teeth erupted,
      hence for further analysis we restricted the subjects to 18 boys and 29 girls who
      were classified as dental age IIIC-IVA (according to Hellman's classification).
      Multiple linear regression analysis was employed using the number of DMF teeth as
      a dependent variable. When we included the variables for the Ca/T-Pro ratio,
      numbers of erupted permanent teeth, sex and salivary flow rate into the model as
      independent variables, there was a statistically significant association (P <
      0.05) between the Ca/T-Pro ratio and the numbers of DMF teeth. However, in other
      models there was no significant association between the numbers of DMF teeth with
      Ca concentration, Ca flow rate, total protein concentration, or total protein
      flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538063
TI  - [Bone mineral density of the lumbar spine and its relation to biological and
      lifestyle factors in middle-aged and aged Japanese women (Part 3). Relationships
      of physical fitness and lifestyle factors to bone mineral density in
      premenopausal and postmenopausal women].
AB  - We recruited community-dwelling women for participation in a study to investigate
      the effects of risk factors in lifestyle on bone mineral density (BMD). The
      subjects were 177 women aged 35 years and over living in a rural area in Fukui
      Prefecture. Their BMD of the lumbar spine (L2-L4) was determined by dual energy X
      ray absorptiometry (DXA). In addition to measurements of height, body weight and
      grip strength, the lifestyles of the women, including physical load in work,
      sporting activities, smoking habits, calcium intake, and history of bone fracture
      were interviewed in detail. Adjusted for age, the BMD significantly correlated to
      body weight (r = 0.337, p < 0.05 for premenopausal women and r = 0.289, p < 0.01
      for postmenopausal women) and body mass index (kg/m2) (r = 0.291, p < 0.05 for
      premenopausal women and r = 0.190, p < 0.05 for postmenopausal women). These
      results indicated the lower body weight to be a risk factor for the osteoporotic
      process in middle-aged and aged women. With respect to the grip strength as a
      physical fitness indicator, a significant correlation coefficient (r = 0.267, p <
      0.01) with BMD was obtained for postmenopausal women independent of age and body
      weight. In univariate analysis, BMD showed no significant correlations with
      sporting activities, smoking habits, lower back pain and history of bone fracture
      for either premenopausal women or postmenopausal women.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8538064
TI  - Immunomodulatory effects of Maharishi Amrit Kalash 4 and 5 in mice.
AB  - To evaluate the immunomodulatory effects of two kinds of Ayurvedic food
      supplements (Maharishi Amrit Kalash 4 and Maharishi Amrit Kalash 5, M-4 and M-5),
      superoxide anion (O2-) production of peritoneal macrophages and the response of
      spleen cells to concanavalin A (Con A) were examined in mice given an aqueous
      emulsion of M-4 and M-5 p.o. at doses of 50 and 100 mg/kg for 10 days. O2-
      production of peritoneal macrophages in the M-5 (50 mg/kg)-treated group was
      significantly higher than that in the control group. The indices of stimulation
      of spleen cells by Con A were significantly (3 to 4 times) higher in groups
      treated with M-4 and M-5 at all doses than in the control group. These results
      indicate that M-4 enhances lymphocyte responsiveness and M-5 enhances not only
      lymphocyte responsiveness but also macrophage function. It is also suggested in
      this study that M-4 and M-5 have mitogenic effects on lymphocytes.

PMID- 8538065
TI  - Fast oscillations of the electro-oculogram in a series of normal subjects.
AB  - Using a newly devised automated electro-oculograph, Nidek EOG-2, the fast
      oscillations (FOs) of the electro-oculogram were recorded in the 120 eyes of 60
      normal subjects. We evaluated the normal means and variability of FO parameters,
      namely the "Rf" value, which is the average ratio in percentage of the maximum
      amplitude in the dark period (AD)/the minimum amplitude in the light period (AL),
      and the "df" value, which is the average difference between AD and AL during the
      FO measurement. No correlation with age was noted in the "Rf" value, although the
      lowest mean value of the "df" was detected in the twenties. Regarding sex, the
      mean levels of the "Rf" and "df" for female subjects were statistically higher
      than those for male subjects in the younger and global age groups. Some hormonal
      factor which can stimulate the metabolic activity of the retinal pigment
      epithelium might have caused this sexual difference.

PMID- 8538066
TI  - Effects of panretinal photocoagulation on photopic ERG in normal rabbit eyes.
AB  - The effects of panretinal photocoagulation (PRP) on photopic ERG were studied in
      normal pigmented rabbit eyes. Photopic ERGs were recorded before PRP and one day,
      one week and 4 weeks after PRP. Markedly reduced amplitude and delayed implicit
      time were observed one day after PRP. Four weeks after PRP, amplitude showed
      subtotal recovery while implicit time, showing tendency of reduction, was still
      significantly delayed. The delay in implicit time and the reduction in amplitude
      after PRP was probably due to serous retinal detachment and/or retinal edema
      caused by breakdown of the blood-retinal barrier. However, the findings at 4
      weeks after PRP might be explained by the reduced number of photoreceptor cells;
      the mild decrease in the amplitude of photopic ERG might be caused by the reduced
      number of cones, while significantly delayed implicit time of the photopic ERG
      might be caused by reduced number of rods.

PMID- 8538067
TI  - Effect of UF-021 on optic nerve head circulation in rabbits.
AB  - The effect of UF-021, a prostaglandin-related compound which has recently become
      available for treatment as an antiglaucoma agent, on the circulation of the optic
      nerve head (ONH) was studied in normal rabbit eyes and in eyes with circulation
      insufficiency induced by endothelin-1 (ET-1). The capillary blood flow in the ONH
      was measured for 5 hours using a hydrogen gas clearance flowmeter, and the
      intraocular pressure (IOP) was also measured. A single instillation of UF-021
      reduced the IOP (maximum reduction: 3.7 mmHg at 2 hours) but had no effect on ONH
      blood flow in normal rabbit eyes. Intravitreal injection of UF-021 reduced IOP to
      a lesser extent (maximum reduction: 1.8 mmHg at 3.5 hours) and significantly
      increased ONH blood flow from 1 to 3.5 hours (maximum increment: 14% of the
      initial value at 1 hour). Pretreatment with intravitreal injection of UF-021 did
      not affect IOP but partly inhibited the ONH blood-flow-decreasing effect of ET-1.
      These results suggest that UF-021 can improve ONH probably by reducing the
      resistance in ONH blood vessels.

PMID- 8538068
TI  - Alteration of lens sulfhydryl groups induced by oxidative stress: Raman
      spectroscopic study of hydrogen peroxide-treated rat lens.
AB  - It has been reported that hydrogen peroxide is present in the aqueous humor and
      its level is increased in cataract patients. To determine the effect of hydrogen
      peroxide on the lens, hydrogen peroxide-treated lenses were monitored by Raman
      spectroscopic methods before and after treatment. The lenses were also examined
      histologically. Excised rat lenses were incubated in the medium containing 100 mM
      of hydrogen peroxide for one hour. Slight lens opacification was observed 3 hours
      after completion of treatment and there was marked opacification by 5 hours.
      Analysis of the Raman spectra from the lens cortex indicated that sulfhydryl
      groups were decreased and disulfide bonds were increased, which suggested that
      exposure to hydrogen peroxide resulted in 2SH --> SS conversion in the lenses. A
      decrease in sulfhydryl groups was observed at one hour after completion of
      treatment and its level was decreased to 60% of the control level by 4 hours
      after treatment. Since the decrease in sulfhydryl groups was observed prior to
      lens opacification, the results indicated that 2SH --> SS conversion may be
      related to the formation of lens opacification.

PMID- 8538069
TI  - Analysis of glycosaminoglycans of subretinal fluid in rhegmatogenous retinal
      detachment--preliminary report.
AB  - To determine the correlation between the types of glycosaminoglycans (GAGs) and
      the features of rhegmatogenous retinal detachment, we analyzed the types of GAGs
      in the subretinal fluid of 20 eyes with rhegmatogenous retinal detachment. The
      GAGs were analyzed by cellulose acetate two-dimensional electrophoresis.
      Hyaluronic acid alone (HA type) was found in 10 of the 20 eyes. A combination of
      chondroitin sulfate (chSA) and HA was present (chSA type) in 3 of the 20 eyes. A
      combination of dermatan sulfate (DS) and HA (DS type) was present in 7 of the 20
      eyes. No correlation was found between the type of GAGs and the extent, the
      duration of detachment, location, size or type of break in the 20 eyes. Some
      correlation was found between the type of GAGs and the grade of vitreous haze,
      proliferative vitreoretinopathy (PVR) and the number of surgeries. Retinal
      detachment with a demarcation line resulted in subretinal strand formation in the
      DS type eyes, while no such formation was seen in the subretinal space of the
      eyes of the chSA type. Vitreous haze of grade ( ) was seen in one eye of the DS
      type, but not seen in the other types. All 3 eyes with PVR of grade C were the DS
      type. The 2 eyes with reoperated surgeries were the DS type. The presence of DS
      may indicate an advanced condition of retinal detachment.

PMID- 8538070
TI  - Immunohistochemical proof of intraneural localization of herpes simplex virus in
      experimental retinitis.
AB  - A unilateral intravitreal inoculation of herpes simplex virus type 1 (HSV-1)
      induced bilateral retinitis and encephalitis in the rat. Immunohistochemistry was
      employed to clarify the pathway of transmission of HSV-1 from the inoculated eye
      to the contralateral eye, and to identify localization of the viral antigen in
      the retina, optic nerve and brain. At an early stage of the post-inoculation
      period, HSV-1 immunoreactivity was first seen in the cytoplasm of Muller cells
      and then in various cells of the inner nuclear layer in the inoculated eye. At a
      later stage, HSV-1 immunoreactivity was seen in some retinal ganglion cells and
      optic nerve fibers in the inoculated eye. In the brain, HSV-1 was found in the
      optic chiasm, bilateral primary visual centers (bilateral suprachiasmatic nuclei,
      bilateral lateral geniculate nuclei, bilateral superior colliculus and bilateral
      pretectum) and bilateral visual cortex. HSV-1 was also demonstrated in the
      retinal ganglion cells, neural cells in the inner nuclear layer, and Muller cells
      in the contralateral eye. We found that HSV-1 antigen in the retina of the
      contralateral eye was transmitted through the optic nerve, visual pathway and
      nuclei, but not through the blood stream.

PMID- 8538071
TI  - The ultrastructural study of ribosomes in photoreceptor inner segments of the pcd
      cerebellar mutant mouse.
AB  - Ultrastructural changes in the distribution of free ribosomes in photoreceptor
      inner segments in relation to photoreceptor degeneration in Purkinje cell
      degeneration (pcd) were studied in mutant mice reared under cyclic light and
      sacrificed at 30 and 120 postnatal days. On postnatal day 30, some photoreceptors
      appeared to be normal whereas others had degenerated to varying degrees with
      numerous spherules in the extracellular space surrounding degenerating inner
      segments. By postnatal day 120, retinal degeneration had progressed with a marked
      loss of photoreceptors. The distribution of free ribosomes in the mutant inner
      segments was random, clustered, or uniform. This was distinct from normal control
      retinas in which random distribution predominated. Markedly degenerated inner
      segments contained sparse ribosomes which coalesced in small aggregates. These
      changes in ribosome distribution seemed to be associated with the extent of
      photoreceptor degeneration. The significance of these changes in ribosome
      distribution, in particular clustered distribution, is discussed together with
      our previous findings.

PMID- 8538072
TI  - Optic neuropathy and acute transverse myelopathy in primary Sjogren's syndrome.
AB  - A case of Sjogren's syndrome with optic neuropathy and acute transverse
      myelopathy mimicking multiple sclerosis is described. The patient suddenly lost
      her visual acuity resulting in a permanent visual deficit in spite of the massive
      steroid therapy given. During the treatment the patient showed dry eye symptoms
      and was finally diagnosed as having primary Sjogren's syndrome. It is suggested
      that primary Sjogren's syndrome should be considered in the differential
      diagnosis of neurologic disorders that resemble multiple sclerosis.

PMID- 8538073
TI  - Studies on development of visual acuity in infants measured by the Teller Acuity
      Cards.
AB  - In order to confirm the reproducibility of visual acuity measurements in infants
      and to elucidate the cause of the plateau and decrease in the developmental curve
      between the ages of 9 and 15 months, we have retrospectively studied visual
      acuity measured by the Teller Acuity Cards (TAC) in infants aged 2 to 28 months.
      The visual acuity measured by TAC was higher than that obtained by the
      conventional preferential looking (PL) method in infants until the age of 14
      months. No statistically significant difference was observed between the first
      eye and the second (fellow) eye measurements. Although monocular visual acuity
      decreased in infants aged from 9 to 12 months, binocular visual acuity showed an
      increase in the same age group. The first binocular measurement was better than
      the last binocular measurement on the same day. Although the first binocular
      measurement showed an increase in infants aged from 9 to 15 months, the second
      binocular measurement decreased in the same age group. Our results suggest that
      all these phenomena mentioned above are likely to be due to the psychological or
      behavioral rejection to the examinations.

PMID- 8538074
TI  - Blepharophimosis, ptosis, epicanthus inversus, telecanthus, amblyopia, and
      menstrual abnormality in sisters.
AB  - Two sisters with blepharophimosis, ptosis, epicanthus inversus, and telecanthus
      were examined. Both patients also had amblyopia in the right eye and menstrual
      abnormalities associated with elevated serum luteinizing hormone and follicle
      stimulating hormone. The patients' father was suspected of having
      blepharophimosis and ptosis. It is possible that the blepharophimosis syndrome
      observed in this family is of autosomal dominant inheritance. We believe that
      this condition of blepharophimosis, ptosis, epicanthus inversus, telecanthus,
      amblyopia, and menstrual abnormality found in our patients may be rare, and that
      the menstrual abnormality in these patients may be associated with ovarial
      failure.

PMID- 8538075
TI  - Bilateral microphthalmos with poor visual acuity, high hyperopia, and
      papillomacular retinal folds in siblings.
AB  - Ophthalmological examinations were carried out on a 4-year old girl and her 2
      year-old brother who have had poor visual acuity since birth. A consanguineous
      relationship was found between the parents. Both children had bilateral
      microphthalmos, poor visual acuity, high hyperopia, and papillomacular retinal
      folds. No ocular coloboma or systemic abnormality was found. We believe that the
      ophthalmic findings in these patients are rare.

PMID- 8538076
TI  - Color-fluorescein relationship in glaucomatous optic nerve damage.
AB  - With the assistance of a computerized image analysis system, the author obtained
      a quantitative evaluation of the color of the optic disc (%R) and the fluorescein
      intensity (%F) in glaucomatous eyes. Patients in various stages of glaucoma were
      studied, including 23 patients with primary open-angle glaucoma (POAG) (23 eyes),
      22 patients with normal-tension glaucoma (NTG) (22 eyes), along with 11 normal
      controls (11 eyes). In both the POAG and NTG groups, %R was lower in eyes with
      more marked visual field defects. The correlation coefficient between %R and the
      stage of visual field defect was 0.794 (P < 0.001) in the POAG group and 0.652 (P
      < 0.001) in the NTG group. Fluorescein intensity also was lower in eyes with more
      marked visual field defects in both groups. The correlation coefficient between
      %F and the stage of visual field defect was 0.897 (P < 0.001) in the POAG group
      and 0.681 (P < 0.001) in the NTG group. In early-stage patients in both glaucoma
      groups, %R was significantly lower than that in the control group (P < 0.05).
      However, there was no significant difference in %R between the NTG and POAG
      groups. In these patients, %F was also lower than that in the control group (P =
      0.001), and was significantly lower in the NTG group than in the POAG group (P =
      0.01). In addition, the pattern of correlation differed between the two groups.
      This difference in the pattern of the optic disk color-fluorescein correlation
      suggests that pathological backgrounds in the development of glaucomatous optic
      disc damage are also different between POAG and NTG.

PMID- 8538077
TI  - Intraocular lens implantation in severely mentally and physically handicapped
      patients.
AB  - Posterior chamber intraocular lenses (PC-IOL) were implanted in 42 eyes of 24
      severely mentally and physically handicapped patients, and the results were
      analyzed in comparison with implants in conventional patients. The patient eyes
      included in this study were 21 eyes of 13 severely mentally retarded patients, 19
      eyes of 10 Down's syndrome patients, and 2 eyes of a patient suffering from
      mitochondrial encephalomyopathy. Surgeries had been performed under general
      anesthesia and resulted in significant improvement in vision and quality of life.
      Severe postoperative complications occurred in one of the eyes of two patients.
      However, the fellow eye of these patients, which also received a PC-IOL
      implantation, showed an uneventful postoperative course. The present study
      indicated that cataract surgery with PC-IOL in patients with severe mental and
      physical handicaps should be considered as an appropriate and promising
      application in spite of the various technical difficulties in the pre- and
      postoperative management of these patients. It is stressed that proper
      calibration of IOL power immediately before surgery under general anesthesia and
      small incision techniques are essential for a successful operation in patients
      with severe mental and physical handicaps.

PMID- 8538078
TI  - A chorioretinal lesion in a patient with Kimura's disease.
AB  - A 47-year-old male patient with Kimura's disease showed a white and slightly
      elevated choroidal lesion surrounded by serous retinal detachment in his left
      eye. Serological examination revealed esinophilia. Swelling in his left cheek had
      been increasing during a period of 20 years, and diagnosis of Kimura's disease
      had been made earlier by biopsy. Fluorescein angiography suggested disturbance of
      choroidal circulation and dysfunction of retinal pigment epithelium. After
      corticosteroid therapy, improvement was seen in the fundus findings, the swelling
      in the cheek and eosinophilia.

PMID- 8538079
TI  - Effect of kanji and kana reading on cerebral blood flow patterns measured by PET.
AB  - To investigate the respective functions of pathways in processing visual
      information from different types of symbols, by positron emission tomography
      (PET) we examined the effect on cerebral blood flow (CBF) of reading the Japanese
      morphogram (kanji) versus the syllabogram (kana). Nine Japanese men were
      presented with three visual conditions in random order 2 minutes before the scan:
      eyes open controls, kanji morphogram reading, and kana syllabogram reading. Three
      words written in kanji or kana were shown, and subjects were instructed to read
      them silently and to identify the word unrelated logically to the other two. The
      reading and analyzing tasks activated wide areas of vision-related cortices. The
      comparison of the kanji and kana readings showed higher metabolism, with the
      former only in the posterior part of the primary visual cortex. Most of the CBF
      increases were common for both stimuli, although the patterns of these increases
      differed slightly. The correlation matrix of CBF change in the left hemisphere
      showed a ventral connection in kanji reading and a dorsal connection in kana
      reading. Our results suggest there is a functional differentiation in the brain
      between patterned and sequential perception when reading Japanese morphograms and
      syllabograms.

PMID- 8538080
TI  - [Two cases of intrapulmonary lymph node associated with either progressive
      systemic sclerosis or idiopathic pulmonary fibrosis].
AB  - We encountered 2 cases of intrapulmonary lymph node. Case 1 was in a 48-year-old
      woman who had been given a diagnosis of progressive systemic sclerosis. Case 2
      was in a 49-year-old woman with idiopathic pulmonary fibrosis. In each patient, a
      follow-up chest CT scan showed a pulmonary nodule, which could not be seen on
      chest X-ray film. Each nodule has an irregular margin and a linear shadow
      resembling pleural indentation. Histological examination of the open biopsy
      specimens revealed that these nodules were intrapulmonary lymph nodes surrounded
      by interstitial pneumonia. Previous case reports and these 2 cases indicate that
      unless a thoracotomy is done intrapulmonary lymph nodes are difficult to
      distinguish from lung cancers.

PMID- 8538081
TI  - [A case of Rendu-Osler-Weber syndrome and pulmonary arteriovenous fistula].
AB  - A 65-year-old man with Rendu-Osler-Weber syndrome was admitted to the department
      of brain surgery at our hospital because of left hemiplegia and a right cerebral
      mass seen on a computerized tomogram of the brain. A brain abscess was found
      during surgery. Then the patient had pneumonia. He received antibiotics and
      recovered, but his PaO2 remained low. He was transferred to our department for
      evaluation of hypoxia. Thoracic computerized tomography showed a nodular lesion
      connected to a vascular shadow. Angiographic examination showed a pulmonary
      arteriovenous fistula and other vascular abnormalities. He was not dyspneic or
      cyanotic, but his hypoxia, low diffusing capacity, and brain abscess were thought
      to be caused by the pulmonary arteriovenous fistula. The fistula was embolized
      with coils via a percutaneous catheter, after which oxygenation and diffusing
      capacity improved.

PMID- 8538082
TI  - [A case of mycosis fungoides with pulmonary involvement: effect of etoposide and
      prednisolone].
AB  - Persistent coughing and bloody sputum developed in a 75-year-old man with mycosis
      fungoides. Chest X-ray films on admission showed combined patterns of alveolar
      and interstitial shadows in both lung fields. Histological examination of the
      transbronchial lung biopsy specimen revealed patchy infiltration of mycosis
      fungoides cells in alveolar septa. VEPA chemotherapy was ineffective against skin
      lesions and caused bacterial pneumonia, but combined treatment with etoposide
      (200 mg, once a week) and prednisolone (30 mg, 3 days per week) resulted in
      remission. The patient has been taking oral etoposide and prednisolone regularly,
      and has been free of skin and pulmonary lesions for two years. Combined therapy
      with low-dose etoposide and prednisolone may be worth trying in cases of advanced
      mycosis fungoides with pulmonary involvement.

PMID- 8538083
TI  - [Diffuse panbronchioliltis associated with bullous pemphigoid].
AB  - A 64-year-old woman complained of multiple blisters in 1990. She had had a
      productive cough since 1975. Immunofluorescence study of a specimen obtained from
      a skin biopsy showed staining in a linear pattern for both IgG and C3 in the
      epithelial basement membrane zone (BMZ) of the dermal-epidermal junction, and a
      high titer of anti-BMZ antibody. These findings led to the diagnosis of bullous
      pemphigoid. Corticosteroid therapy was started, and resulted in some
      stabilization of the skin lesion. Exertional dyspnea and a productive cough
      developed gradually, and the patient was referred to our department in 1992.
      Chest X-ray film and CT findings revealed a diffuse granular shadow and
      bronchiectatic change, predominantly in the lower lung fields. Laboratory tests
      showed a high titer of cold hemagglutinin and a high level of serum
      immunoglobulin A. Pulmonary function tests showed a combined destructive
      restrictive defect and hypoxemia (PaO2 = 58.5 Torr). From these findings diffuse
      panbronchiolitis was diagnosed. A low dose of erythromycin alleviated the
      patient's pulmonary symptoms and improved the chest radiographic findings.

PMID- 8538084
TI  - [Hypersensitivity pneumonitis caused by a home humidifier].
AB  - A 33-year-old man was admitted complaining of a fever, dyspnea, and a dry cough
      almost every night since December of 1992. He had been using an ultrasonic
      humidifier at home. The chest CT scan and roentgenogram showed bilateral
      reticulonodular shadows. After admission, the symptoms resolved spontaneously.
      These findings were suggestive of hypersensitivity pneumonitis. After analysis of
      fluid obtained by bronchoalveolar lavage and of a specimen obtained by
      transbronchial biopsy, "humidifier lung" was diagnosed. Ten species of
      microorganisms were isolated from the water left in the patient's humidifier. On
      precipitation and complement fixation tests of the patients serum, the results
      were positive for three of those microorganisms: Flavobacterium multivorum,
      Yersinia pseudotuberculosis, and Aureobacterium liquefaciens. The titer on the
      complement fixation test increased immediately after a provocation test. The
      laboratory results suggest that at least one of these three microorganisms was
      the causative antigen in this case.

PMID- 8538085
TI  - [Relationship between sleep stage and blood pressure variability during apnea in
      patients with sleep apnea syndrome].
AB  - A marked transient increase in blood pressure can occur at the end of each apneic
      period in patients with sleep apnea syndrome (SAS) and SAS may be a risk factor
      for cerebrovascular disease. To estimate blood pressure variability during apnea
      arterial blood pressure was directly and continuously recorded, and the transient
      increase in blood pressure in each sleep stage was assessed. Polysomnography was
      done in 5 men with SAS: arterial blood pressure, oxygen saturation, and
      respiratory curves were recorded. The maximum arterial blood pressure during the
      apneic period was compared with that at the end of apnea. The transient increase
      in blood pressure was 32.2 +/- 5.8 mmHg (mean +/- S.E.) for systolic pressure and
      18.2 +/- 2.1 mmHg for diastolic pressure. During REM sleep, the values were 38.8
      +/- 6.6 mmHg for systolic pressure and 23.4 +/- 2.2 mmHg for diastolic pressure.
      The increase in arterial blood pressure was significantly higher during REM sleep
      than during N-REM sleep (p < 0.05). This wide variation in blood pressure
      suggests that SAS is a risk factor for cerebrovascular disease, and that SAS may
      promote essential hypertension.

PMID- 8538086
TI  - [Effects of inhaled oxitropium bromide, an anticholinergic drug, on pulmonary
      hemodynamics in patients with chronic obstructive pulmonary diseases].
AB  - We studied the effects of the inhaled anticholinergic agent oxitropium bromide
      (Ox) on pulmonary hemodynamics in eleven patients with chronic obstructive
      pulmonary disease. All the patients underwent right heart catheterization and
      seven of them underwent an incremental ergometer exercise test while in the
      supine position. Pulmonary hemodynamics and arterial blood gases were measured at
      rest and during maximal exercise, before and 30 minutes after inhalation of 2
      puffs (200 micrograms) of Ox. Inhalation of Ox did not significantly change
      pulmonary hemodynamics at rest. The mean pulmonary arterial pressure and the mean
      pulmonary capillary wedge pressure during exercise decreased significantly (from
      40.3 +/- 4.6 to 37.7 +/- 3.9 mmHg, and from 20.4 +/- 3.5 to 17.1 +/- 2.7 mmHg,
      respectively, mean +/- SE). However, neither cardiac output nor pulmonary
      vascular resistance changed with inhalation of the drug, at rest or during
      exercise. We therefore conclude that this commonly used dose of Ox does not
      directly affect the pulmonary vascular system. The small but significant
      decreases in pulmonary arterial pressure and pulmonary capillary wedge pressure
      with Ox may have been indirect effects, caused by bronchodilation.

PMID- 8538087
TI  - [Effects of intravascular latex injection on factors responsible for acute lung
      injury].
AB  - To study the contribution of phagocytosis to the development of acute lung
      injury, latex particles (2 x 10(9)/kg; mean diameter, 2.84 microns) were injected
      intravenously or intra-arterially into guinea pigs. 125I-labelled albumin was
      injected to estimate the degree of lung injury, and 51Cr-labelled red blood cells
      were injected to correct for blood contamination in the samples. A control group
      was given saline. Four hours after the injections, the animals were killed,
      bronchoalveolar lavage was done, and the lungs were examined histopathologically.
      Animals that had received intravenous and intra-arterial injections of latex
      particles had more lung water and more pulmonary albumin leakage than animals
      that had received saline. Histopathological examination revealed massive
      accumulation of latex in the reticuloendothelial system. These findings suggest
      that the phagocytic process in the reticuloendothelial system plays a role in the
      development of lung injury in guinea pigs.

PMID- 8538088
TI  - [Primary lung cancer presenting as spontaneous pneumothorax].
AB  - Pneumothorax is a rare manifestation of lung cancer. The mechanism by which
      pneumothorax occurs in lung cancer is not clear, and differing views have been
      expressed. Among 180 adults who presented with spontaneous pneumothorax from 1980
      to 1992, eight had lung cancer: seven had squamous cell carcinoma and one had
      adenocarcinoma. All were men between 50 and 81 years old (average age, 66 years).
      In all patients, the pneumothorax occurred on the same side as the carcinoma.
      Thoracotomy was done in four patients. The results obtained by surgery indicated
      that pneumothorax may be caused by: 1) direct invasion of tumor into the pleura
      (patient 1); 2) rupture into the pleural space of dilated alveoli that are distal
      to the site of stenotic bronchial cancer (patient 7); 3) rupture into the pleural
      space of alveoli that had become distended to compensate for atelectasis due to
      obstructive bronchial cancer (patient 6); and 4) unknown (patient 2). These
      results suggest that lung cancer should always be considered as a possible cause
      of spontaneous pneumothorax in older patients.

PMID- 8538089
TI  - [Clinical characteristics and outcome of 508 patients with hyperventilation
      syndrome].
AB  - The characteristics of hyperventilation syndrome (HVS) were studied in 508
      patients who visited our hospital over 11 years. Information regarding symptoms
      and laboratory data was collected from the clinical records, and outcome was
      surveyed with a questionnaire mailed to all patients. Patients with acute HVS
      ranged in age from 5-85 years, and acute HVS was particularly prevalent among
      women in their late teens. Triggers of HVS included anxiety, nausea & vomiting,
      and fever due to the common cold. The primary symptoms were dyspnea and numbness,
      but these differed from the symptoms that appeared during a provoked attack, Half
      of the patients had no underlying disorder, but the others were suffering from
      neurosis, cardiovascular disorders, or other diseases. These characteristics of
      acute HVS did not differ from those seen in patients in whom the diagnosis of HVS
      was confirmed with arterial blood gas analysis. Half of the patients recovered
      without treatment, and the others underwent paper-bag rebreathing or intravenous
      infusion of sedatives. The prevalence of chronic HVS was 2% and almost all those
      patients were middle-aged women. In contrast, the questionnaire revealed that
      half of the patients had repeated HVS attacks. In 10% of the patients, these
      attacks persisted for more than 3 years. Many of these patients reported that
      they sighed frequently and felt air hunger while in remission. These findings
      were compatible with the criteria for chronic HVS. Therefore, it may be possible
      to diagnose HVS from symptoms alone, without hyperventilation provocation tests.
      In conclusion, these data underscore the importance of clinical symptoms in the
      diagnosis of HVS.

PMID- 8538090
TI  - [Role of serotonin in impaired gas exchange during pulmonary embolism].
AB  - Although serotonin has been reported to play a substantial role in
      cardiopulmonary dysfunction, the quantitative effects of serotonin, released from
      activated platelets, on the development of alveolar flooding and on impaired gas
      exchange in pulmonary embolism have not been systematically investigated. To
      elucidate the effects of serotonin on pulmonary hemodynamics, accumulation of
      edema fluid in alveolar space, and impairment of gas exchange in acute pulmonary
      embolism, 20 mongrel dogs were given 0.4-0.6 g/kg of glass beads with a diameter
      of 100 microns, via the internal jugular vein. Before and after embolization,
      pulmonary hemodynamics, systemic hemodynamics, blood gases, and the distribution
      of ventilation-perfusion ratios (VA/Q) in the lung were measured, with and
      without a newly developed selective antagonist of the serotonin S2 receptor, DV
      7028. VA/Q distribution was determined by applying the multiple inert gas
      elimination technique. After glass-bead embolization, the animals that did not
      receive DV-7028 showed significant increases in pulmonary arterial pressure and
      in extravascular lung water, widened alveolar-arterial O2 tension differences,
      and appreciable development of low VA/Q areas (0 < VA/Q < or = 0.1). These
      changes were prevented in the animals that received DV-7028. However, DV-7028 did
      not affect the formation of high VA/Q areas (VA/Q > 10). In conclusion, in acute
      canine pulmonary embolism serotonin not only induces pulmonary hypertension and
      pulmonary edema, but also worsens gas exchange through the formation of low VA/Q
      areas.

PMID- 8538091
TI  - [Inhaled beclomethasone in long-term management of asthma: optimal dose and
      optimal duration of treatment].
AB  - We studied the usefulness of 24 weeks of therapy with inhaled beclomethasone
      dipropionate (BDP) in the management of mild and moderately severe asthma in
      adults. To determine the optimal dose and treatment duration, the patients were
      divided into three groups. Patients in group I (n = 10) were treated with
      bronchodilators but no BDP. Patients in group II (n = 12) received
      bronchodilators and 450 micrograms/day of BDP. Patients in group III (n = 17)
      received bronchodilators and 900 micrograms/day of BDP. BDP was inhaled via a
      large spacer (Volumatic). Asthma scores were measured before treatment began, and
      again every 2 weeks for the duration of the study (26 weeks). Peak expiratory
      flows (PEF) were measured before treatment began, 2 weeks after treatment had
      begun, and again every four weeks until the end of the study. Vital capacity,
      FEV1, and bronchial reactivity to methacholine were measured before treatment
      began, and again 12 weeks and 24 weeks after it had begun. Adrenocortical
      function in patients in group III was measured with a rapid ACTH test, at the
      same time as the pulmonary functions were measured. The results were: 1) Asthma
      scores decreased more in patients who received the higher dose of BDP than in
      those who received the lower dose, especially during the second 12 weeks. 2)
      After two weeks of treatment, %PEF had increased significantly in both groups
      that received BDP, but after six weeks of treatment there was no further
      improvement. %PEF did not improve in the group given bronchodilators only. 3) In
      the patients whose baseline %PEF was less than 80%, only the higher dose of BDP
      significantly increased %PEF. 4) Only the higher dose of BDP increased the %VC,
      the FEV1%, and the PD20 for methacholine. 5) Asthma type and severity were not
      related to the usefulness of BDP therapy. 6) Results of the rapid ACTH test
      indicated that the higher dose of BDP did not suppress adrenocortical function.
      These data indicate that 900 micrograms of BDP per day is more effective than 450
      micrograms/day as initial therapy for long-term management of mild or moderate
      asthma in adults, and that the dose of BDP should be reviewed after 3 months of
      treatment. Patients in whom asthma is well-controlled may tolerate a reduction in
      dose, and those in whom asthma is not well-controlled may require a higher dose.

PMID- 8538092
TI  - [Transport of ions across alveolar epithelial cells in resected human lungs].
AB  - Little information is available regarding the effect of ion transport agonists
      and antagonists on ion transport in the human lung. Therefore, we studied ion
      transport in lungs resected from patients with lung cancer. A test solution of 45
      ml of isosmotic albumin was instilled into one segment of a resected lobe within
      10 min of resection. Because protein leaves the air space very slowly, the
      concentration of alveolar protein over 4 h was used to quantify the volume of
      alveolar fluid. Ion transport was measured from the changes in ion concentrations
      and the volume of alveolar fluid. In the basal condition, the net efflux of Na+
      and Cl- were 4.66 +/- 0.83 mEq/l/h and 3.52 +/- 0.84 mEq/l/h, respectively. In
      contrast, the net influx of K+ was 0.44 +/- 0.07 mEq/l/h. Amiloride (10(-5) M),
      an inhibitor of apical Na+ uptake, ouabain (10(-3) M), an inhibitor of Na(+)-K+
      ATPase, and hypothermia (8 degrees C) reduced the efflux of Na+ and Cl-. Ouabain
      and hypothermia increased the net influx of K+. Terbutaline (10(-3) or 10(-4) M)
      increased the efflux of Na+ and Cl-, but did not affect the influx of K+.
      Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced
      increase in the transport of Na+ and Cl-. Alveolar fluid clearance was closely
      correlated with Na+ transport and with Cl- transport. However, the values of Na+
      transport were greater than those of Cl- transport. These data suggest that Na+
      transport is accompanied by Cl- transport and fluid movement out of the alveolar
      space in resected human lungs.

PMID- 8538093
TI  - [Histological evaluation of lung cancer with T2-weighted magnetic resonance
      images].
AB  - We investigated the differences in signal intensity of lung cancer tissue and non
      cancerous lung tissues on T2-weighted magnetic resonance (MR) images. MR images
      were obtained from patients with squamous cell carcinoma (n = 6), adenocarcinoma
      (n = 5), small cell carcinoma (n = 5), and large cell carcinoma (n = 1). To
      compare the MR signal intensity between tissues, we calculated the signal
      intensity ratios for tumor/skeletal muscle and lung/skeletal muscle. The MR
      signal intensity for each tissue was measured with a densitometer and T2-weighted
      MR images with a similar window and a center. The value of the signal intensity
      ratio for squamous cell carcinoma (3.26 +/- 0.76) was greater than those for
      adenocarcinoma (1.99 +/- 0.50, p < 0.05), small cell carcinoma (2.35 +/- 0.60),
      large cell carcinoma (2.46), and non-cancerous lung tissues (1.70 +/- 0.68, p <
      0.02). The values of the MR signal intensity ratio for non-cancerous lung tissues
      were 2.00 for a collapsed lung, 0.93 for a firotic lung, and 2.18 for a fibrotic
      lung with obstructive pneumonia. The results suggest that the MR signal intensity
      ratio for pathologic tissues/normal skeletal muscle can be a useful indicator for
      qualitative and quantitative MR imaging diagnosis.

PMID- 8538094
TI  - [Hypopnea according to various definitions and coexisting arousal response in
      patients with sleep-disordered breathing].
AB  - Hypopnea is a type of sleep-disordered breathing, and the apnea plus hypopnea
      index (AHI) is usually computed to diagnose this condition. Nevertheless, there
      is no consensus on the definition of hypopnea. To arrive at a reasonable
      definition, we examined the relationship between arousal response and hypopnea as
      defined in various ways, in polysomnographs of 20 patients with sleep-disordered
      breathing. Hypopnea was defined as a 50% reduction in thoraco-abdominal movement
      of various durations (all of which were more than 10 sec) and coexisting oxygen
      desaturation of various degree. The ratio of coexisting arousal response for
      hypopneas was higher when hypopnea was defined as having a relatively long
      duration and relatively deep desaturation, but more arousal responses were
      missed. 1) When the threshold duration for hypopnea was fixed at 10 sec, the
      following results were obtained: With desaturation thresholds of 4% and 2%, the
      mean ratios of missed arousals were 37% (range, 1-85%) and 12% (range, 0.5-35%),
      respectively. The hypopneas with only 2% desaturation had coexisting arousal
      responses with a mean frequency of 49% (range, 27-89%). 2) When desaturation was
      not included in the definition, the following results were obtained: Hypopneas
      lasting less than 15 sec had lower frequencies of a coexisting arousal response
      than did those of longer duration. When the threshold duration for hypopnea was
      15 sec, the mean ratio of missed arousal was 16.2% (range, 1.6-32.9%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8538095
TI  - [Septic lung caused by methicillin-resistant Staphylococcus epidermidis].
AB  - A 55-year-old man was admitted to our department one month after resection of
      rectal carcinoma, with complaints of fever and general malaise. Shock developed
      rapidly after admission. The chest X-ray film and computed tomography showed
      diffuse small nodular shadows and bilateral pleural effusion. Septic lung caused
      by Methicillin-resistant Staphylococcus epidermidis (MRSE) was diagnosed from the
      results of a bacteriological study. This bacteria is a Coagulase Negative
      Staphylococcus (CNS). Chemotherapy with Minocycline and Cefotiam was effective.
      Characteristic radiologic features of this case may be related to the early stage
      of adult respiratory distress syndrome (ARDS) and septic pulmonary microembolism.

PMID- 8538097
TI  - [Thymic Hodgkin's disease with cystic variants: a case report].
AB  - We report an unusual case of thymic Hodgkin's disease with cystic variants. The
      patient complained of nodules in his neck. Chest radiographs showed a mass with
      cystic lesions in the anterior mediastinum. Although Hodgkin's disease was
      suspected from pathologic examination of biopsy specimens of the neck nodules,
      the mediastinal and neck masses could not be precisely diagnosed until a median
      sternotomy was done. The surgically excised mediastinal masses revealed thymic
      Hodgkin's disease with cystic lesions. The patient has done well after
      chemotherapy and radiotherapy. Thymic Hodgkin's disease with cystic variants is
      very rare and only seventeen cases of this disease have been reported.

PMID- 8538098
TI  - [A case of thymic squamous cell carcinoma successfully treated with curative
      resection].
AB  - A case of rare thymic squamous cell carcinoma was reported. A 46-year-old female
      was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest
      CT showed anterior mediastinal tumor and histological diagnosis of squamous cell
      carcinoma was made by needle biopsy under CT guide. Esophagus and lung were no
      abnormal findings, we thought the primary region was thymus. On mid-sternotomy,
      anterior mediastinal tumor was resected with thymus, right phrenic nerve and
      pericardium, however it was not direct invasion to heart, great vessels, lung and
      chest wall. Resection of peripheral fatty tissue and dissection of mediastinal
      lymph nodes as much as possible, it was not capsular invasion and mediastinal
      lymph nodes metastasis and complete curative resection was able to perform.
      Additional radiation therapy was done, post-operative course was uneventful.

PMID- 8538096
TI  - [Pulmonary malignant fibrous histiocytoma treated with cisplatin plus etoposide
      followed by surgery].
AB  - A 47-year-old woman was admitted to our hospital with a mass shadow in the upper
      lobe of the right lung. Undifferentiated carcinoma was diagnosed after
      transbronchial biopsy. Combination chemotherapy consisting of cisplatin and
      etoposide was given. After two cycles of chemotherapy, partial response was
      obtained, and surgery was done because there was no evidence of lymph node
      metastasis or distant metastasis. After successful surgery, malignant fibrous
      histiocytoma was diagnosed because histological examination revealed the typical
      storiform pattern and most tumor cells showed positive cytoplasmic staining for
      alpha 1-antitrypsin, alpha 1-antichymotrypsin, and CD68. No evidence of another
      primary lesion was found, so this tumor was thought to be a pulmonary malignant
      fibrous histiocytoma. Cisplatin and etoposide have synergistic effect in vivo,
      and this combination is widely used as a standard regimen for small cell lung
      cancer and other malignancies. It might also be effective against pulmonary
      malignant fibrous histiocytoma.

PMID- 8538099
TI  - [Expedient technique of aortic annular enlargement in aortic valve replacement].
AB  - The extended aortoplasty through the aortic annulus at the posterolateral part,
      Nicks and co-workers have reported, is applied in case of aortic valve
      replacement for the narrow aortic annulus, while we have often encountered some
      problems of bleeding from suture lines of aortoplasty or a left atrial wall
      defect of the atrial attachment at the aortic root. We report an idea for
      resolving these problems by means of using a patch for the aortoplasty lined with
      an equine pericardium on the inner side which has an excess part inferiorly
      folded up to the outer side. This technique may be effective for hemostasis of
      suture lines and easier to close the defect of the left atrium with the
      pericardial excess part.

PMID- 8538100
TI  - [Removal of infected pacemaker leads in the elderly under extracorporeal
      circulation: two case reports and review of Japanese literature].
AB  - Two elder cases in whom infected pacemaker leads were removed under
      extracorporeal circulation (ECC) are reported. The leads could not be with drawn
      without direct sharp dissection under ECC because they had become firmly encased
      with fibrous tissue within the right ventricle. Postoperative courses were
      uneventful and neither of these patients has experienced recurrent infection to
      date. Removal with ECC seems to be a safe and effective procedure even in the
      elderly, provided that cardiac function is good.

PMID- 8538101
TI  - [A case of failure of mitroflow pericardial valve with severe hemolytic anemia].
AB  - A 49-year-old woman who underwent mitral valve replacement with 29 mm Mitroflow
      pericardial valve in 1985 started to have severe hematuria, anemia and icterus
      around May 1994. She was diagnosed to have mitral regurgitation with hemolytic
      anemia due to structural deterioration of the prosthetic valve. She underwent
      replacement of the prosthetic valve with 29 mm St. Jude medical mechanical valve,
      which alleviated the symptoms remarkably. The explanted valve showed an extensive
      cuspal tear and prolapse close to the commissure and poor endothelialization of
      the inflow surface of the frame. In our experience the rate of structural
      deterioration of the Mitroflow valve is so high that we discontinued using this
      bioprosthesis.

PMID- 8538102
TI  - [Bronchopleural fistula following the use of automatic stapling devices for lung
      cancer].
AB  - We compared automatic stapling with hand suturing in the rate of bronchopleural
      fistula. Twenty two hundred forty one patients of 25 hospitals, who were
      performed lobectomy or pneumonectomy for lung cancer from the year of 1990 to
      1992, were investigated about the occurrence of bronchopleural fistula. The rate
      of bronchopleural fistula following lobectomy were 0.9% (11/1,227 cases) in
      automatic stapling, and 1.1% (8/753 cases) in hand suturing; there was no
      difference. However, there was a higher rate of the fistula with the use of
      automatic stapling devices in pneumonectomy. The rate was 11.2% (11/98 cases) in
      automatic stapling, and 1.2% (2/166 cases) in hand suturing. Automatic stapling
      may lead to bronchopleural fistula in pneumonectomy. Moreover, addition of hand
      suturing to automatic stapling was thought to prevent the fistula.

PMID- 8538103
TI  - [Surgical problem of lung cancer with coexisting acute pulmonary tuberculosis].
AB  - Four patients with coexistent lung cancer and acute pulmonary tuberculosis were
      operated during recent 5 years. All were males and cigarette smokers (B.I. >
      600). Adenocarcinoma were recovered from 3 patients, while the remaining 1 had
      squamous cell carcinoma. Only 1 curative resection was performed for lung cancer.
      In most cases, late stage of the disease was alleged to be a factor contributing
      to the poor prognosis.

PMID- 8538104
TI  - [Use of inferior epigastric artery for coronary artery bypass grafting].
AB  - The usefulness of the free inferior epigastric artery (IEA) as a coronary bypass
      graft was studied. Among 149 patients for coronary bypass grafting (CABG) between
      October 1992 and December 1994, the free IEA was used in 12 patients. The mean
      number of distal anastomosis was 3.7 per patient. The mean distal size of the IEA
      was 1.3 mm in diameter and the mean length was 9.4 cm. The IEA graft was
      anastomosed to the obtuse marginal branch in 5, to the diagonal branch in 4, and
      the right ventricular branch in 3. The proximal anastomosis of the IEA was
      constructed to the ascending aorta in three and to the saphenous vein (SVG) or to
      the internal thoracic artery (ITA) in 4 or 5, respectively. Postoperative
      angiogram demonstrated patent graft in ten and occluded graft in two in whom the
      size of IEA was less than 1.0 mm in distal diameter and the IEA was anastomosed
      to the aorta or to the SVG. The IEA was considered to be useful alternative
      arterial graft when it was used as "interposed graft" of which proximal
      anastomosis was made to the ITA and size-matching of the graft to the coronary
      artery was appropriate. The long-term patency of the graft can determine the true
      efficacy of the IEA for CABG.

PMID- 8538105
TI  - [CABG using Y arterial graft which consists of internal thoracic artery Y
      branched with inferior epigastric artery].
AB  - From December 1994 to April 1995, nine patients were submitted to myocardial
      revascularization using Y arterial graft, which consists of internal thoracic
      artery (ITA) Y branched with inferior epigastric artery (IEA). The age ranged 50
      to 76 (mean age, 67.2 years); seven patients were male. Five patients had three
      vessel CABG and four patients had four vessel CABG. There was no operative
      mortality and no mechanical supports with IABP. Aortic clamping and operative
      time was not longer in this series. Early postoperative angiographic evaluation
      of Y arterial grafts showed that nine ITA grafts were patent (100%) and seven IEA
      grafts were patent (77.8%). Because of the low patency rate of IEA graft, Y graft
      using IEA appears to be an interesting alternative only in patients who have no
      other available conduits.

PMID- 8538106
TI  - [A surgical repair of partial anomalous pulmonary venous drainage to the high
      superior vena cava].
AB  - A 7-year-old boy with partial anomalous pulmonary venous drainage to the high
      superior vena cava (SVC) underwent surgical repair by Williams procedure. Right
      upper pulmonary vein was drained to the left atrium via the SVC and the
      surgically enlarged sinus venosus type ASD. SVC was ligated and divided. SVC was
      then anastomosed to RA appendage pedicle directly. Autologous pericardium was
      patched anteriorly to create a new SVC pathway. The postoperative course was
      uneventful without arrhythmia and cardiac catheterization 1 month postoperation
      revealed no stenosis of the SVC and right upper pulmonary venous return.

PMID- 8538107
TI  - [A case report of acute aortic dissection with aortic regurgitation and cardiac
      tamponade: intimal tear just above commissure of right coronary cusp and left
      coronary cusp].
AB  - A 57-year-old man with acute dissecting aneurysm of the ascending aorta underwent
      immediate operation. Preoperative study showed aortic regurgitation and cardiac
      tamponade. The intimal tear originated just above commissure of right coronary
      cusp and left coronary cusp. The procedure was a combination of direct closure of
      the entry and dissecting space and resuspension of native aortic valve. It was
      preferential of simple intervention limited to the ascending aorta without using
      prosthesis. There was no complication such as aortic valve regurgitation,
      enlargement of the ascending aorta, or persistent of dissection during follow-up
      period of 12 months.

PMID- 8538108
TI  - [A case of supravalvular pulmonary stenosis with atrial septal defect].
AB  - We reported a case of supravalvular pulmonary stenosis with atrial septal defect
      (ASD) in 37-year-old man. Extended pulmonary arterioplasty with the technique of
      Doty's operation for supravalvular aortic stenosis was carried out with bovine
      pericardial patch. Pressure gradient between the right ventricle and the
      pulmonary artery reduced from 90 to 20 mmHg after this operation. Doty's
      technique could be modified and successfully applicable to supravalvular
      pulmonary stenosis.

PMID- 8538109
TI  - [Hemoptysis due to aortopulmonary fistula: a case report of successful surgical
      treatment].
AB  - A 76-year-old man was admitted for recurrent hemoptysis of 3 weeks' duration.
      Chest X-ray revealed lung emphysema, but no findings of thoracic aortic aneurysm.
      The patient's physician attributed to bronchoectasia, and he underwent
      angiography for the purpose of embolization of bronchial arteries. Angiography
      showed a small saccular thoracic descending aortic aneurysm and an aortopulmonary
      fistula. So aneurysmectomy and patch angioplasty was done under partial
      cardiopulmonary bypass. Lobectomy or wedge pulmonary resection was not necessary.
      His postoperative course was uneventful. In case of the patients with hemoptysis,
      the possibility of aortopulmonary fistula should be considered, and computed
      tomography or aortography should be done to rule out other pulmonary diseases.

PMID- 8538110
TI  - [Removal of infected transvenous electrodes associated with giant vegetations
      under cardiopulmonary bypass].
AB  - A 69-year-old man was admitted because of endocarditis with septicemia following
      recurrent fever of one year duration. The patient had underwent implantation of
      DDD pacemaker for complete A-V block 2 years ago. Preoperative echocardiogram
      demonstrated giant vegetations around the intraatrial and intraventricular
      electrodes, however no pathogenic organisms were detected by serial blood
      cultures. Total pacemaker system including infected endocardial electrodes were
      removed under cardiopulmonary bypass successfully, and new epicardial electrodes
      were implanted at the same time. The patient was recovered uneventfully.

PMID- 8538111
TI  - [A case of ruptured thoracoabdominal aortic aneurysm complicated with high aortic
      occlusion].
AB  - We report a rare case of 76-year-old man who developed ruptured thoracoabdominal
      aortic aneurysm complicated with abdominal high aortic occlusion. His left limb
      was amputated due to Buerger's disease. CT showed that the aneurysm extended from
      the descending thoracic aorta to the upper part of the abdominal aorta and its
      had a maximum width of 68 x 83 mm. Angiogram revealed the aortic occlusion at the
      level of the left renal pelvis. We performed emergency operation, which was
      aneurysmectomy and replacement with artificial vascular graft, under femoro
      femoral and subrenal aortic extracorporeal bypass. Because of the severe
      calcification at the subrenal aorta and the weak pulsation of the left renal
      artery, the bypass was placed from the aortic graft to the right lower limb and
      the left renal artery was reconstructed. Abdominal aortic occlusion might
      increase his hypertension and might cause aneurysmal change on the proximal
      aortic wall.

PMID- 8538112
TI  - [A case report of pulmonary sequestration (Pryce I) associated with incomplete
      lobulation of the left lung].
AB  - A 28-year-old man was treated surgically for pulmonary sequestration of Pryce
      type I associated with incomplete lobulation of the left lung. His chief
      complaint was hemoptysis. His chest X-ray film showed a mass lesion behind the
      cardiac shadow. Aortogram revealed a large artery arising from the descending
      aorta and supplying the left basal segment, and venous blood returning into the
      left inferior pulmonary vein. The left basal segment had no pulmonary arteries. A
      bronchogram showed no defects in the bronchial tree. The left basal segment was
      resected successfully. Histological study showed the trunk of the aberrant artery
      to be elastic. Differences between histological types of aberrant arteries in
      pulmonary sequestration of Pryce type I and the pathogenesis of intralobar
      sequestration were discussed.

PMID- 8538113
TI  - [Clinical analysis of lung cancer in patients with chondromatous hamartoma].
AB  - Between 1978 and 1993, 776 patients with lung cancer and 18 patients with
      chondromatous hamartoma were operated on in the department of Surgery II in
      Okayama University Hospital. 3 patients had both lung cancers and chondromatous
      hamartomas. They were all men. Two patients were 65 years old and the other was
      82 years old. They all pointed out them by a medical examination of chest X-ray.
      2 patients had lung cancers and chondromatous hamartomas in the same lobe, the
      other had them in other lobe of the same side. Lung cancer and chondromatous
      hamartoma localized in near area. It was difficult to discriminate chondromatous
      hamartoma between pulmonary metastasis of lung cancer before an operation.

PMID- 8538114
TI  - [A case report of chronic sternal osteomyelitis after thoracic aortic
      aneurysmectomy].
AB  - A 76-year-old man, who was complicated with chronic sternal osteomyelitis after
      thoracic aortic aneurysmectomy was reported. He was treated with local wound care
      and antibiotics for about 3 months, but cutaneous fistula with persistent
      discharge required sternal bone debridement and omental pedicle grafting. After
      this treatment the patient was uneventful. 67Ga scintigram and 67Ga-SPECT may be
      more useful in the diagnosis of this serious complication.

PMID- 8538115
TI  - [Malignant mediastinal lesions with invasion to the superior vena cava].
AB  - Four patients underwent resection of mediastinal malignant tumors with invasion
      to the superior vena cava. Two patients had invasive thymoma, one seminoma, and
      one metastatic mediastinal lymph nodes of unknown origin. Prior to resection of
      the tumor, an ePTFE graft was anastomosed between the innominate vein and the
      right atrium to maintain the venous drainage from the brain and the upper
      extremities. In two patients, the superior vena cava was reconstructed by patch
      angioplasty after the tumor with a part of the vena cava was safely resected. One
      patient died of acute respiratory failure, but the other three are alive and well
      without any evidence of graft obstruction. This safe and useful method in order
      to prevent cerebral congestion during and after resection of the tumor.

PMID- 8538116
TI  - [Effect of tepid cardiopulmonary bypass in coronary artery bypass operation].
AB  - The effect of systemic temperature during cardiopulmonary bypass (CPB) surgery
      was evaluated in 100 patients. The patients were divided into three groups, based
      on systemic temperature during CPB; 28 degrees C, 30 degrees C, or 32 degrees C
      (tepid). Multidose cold crystalloid cardioplegia was administered for myocardial
      protection. Pump flow was maintained at 75 ml/kg/min. Methoxamine hydrochloride
      and phenothiazine were used to maintain systemic perfusion pressures between 60
      and 80 mmHg. Preoperatively, there were no differences between groups in left
      ventricular ejection fraction or extent of coronary artery disease. The time
      required for CPB and weaning from CPB were significantly shorter in the 32
      degrees C group than in either the 28 degrees C or the 30 degrees C group. There
      were significant differences in the doses of methoxamine hydrochloride and
      phenothiazine required in each group. Postoperatively, there were no significant
      differences in the incidence of myocardial infarction, stroke, or 30-day
      mortality between groups. In conclusion, tepid systemic perfusion shortens the
      length of CPB and does not differ significantly from cold perfusion with respect
      to mortality and morbidity.

PMID- 8538117
TI  - [Effects of preserving mitral apparatus on left ventricular systolic function and
      geometry in mitral valve replacement].
AB  - We investigated the left ventricular (LV) systolic function and geometry in
      mitral valve replacement (MVR) with and without preservation of mitral apparatus.
      Five patients had conventional MVR without mitral annulus papillary muscle
      continuity (group C) and five patients had MVR with preservation of the
      continuity (group P). LV cineangiograms were assessed before and one month after
      surgery. LV volume was calculated by the method of Kennedy. Long axis dimension
      is defined as the distance between the apex and the center of mitral orifice in
      right anterior oblique projection. Short axis dimension is defined as the cross
      sectional dimension at the middle point of the long axis. Paired Student's t
      tests were employed to compare the preoperative and postoperative data. LV
      ejection fraction decreased significantly from 69.4 +/- 9.5 to 51.8 +/- 10.5% in
      group C (p < 0.05) and did not change significantly in group P (from 51.6 +/-
      19.9 to 56.8 +/- 12.9%). Fractional shortening of the long axis increased
      significantly from 15.0 +/- 11.8 to 21.2 +/- 14.0% in group P (p < 0.02) and did
      not change significantly in group C (from 16.5 +/- 8.6 to 13.1 +/- 3.3%). Ratio
      of LV end-systolic long axis to short axis dimension increased significantly from
      1.76 +/- 0.31 to 2.12 +/- 0.21 in group C (p < 0.05) and did not change
      significantly in group P (from 1.90 +/- 0.22 to 1.95 +/- 0.22). We conclude that
      the ratio of systolic long to short axis increases, i.e., systolic LV shape
      changes to become longer and slender, and ejection fraction decreases after
      surgery in MVR without preservation of mitral apparatus. Conversely, preserving
      the mitral apparatus in MVR results in no significant change in systolic LV
      function and geometry, because of preserving fractional shortening of long axis.

PMID- 8538119
TI  - [How you can stop smoking].

PMID- 8538118
TI  - [Infectious hospital waste in the Canton Berne. Controversy among the experts on
      dangerous waste].

PMID- 8538120
TI  - [Clarifying concepts. From prevention to promotion].

PMID- 8538121
TI  - [Basic stimulation in geriatric care. Reactivation through the senses].

PMID- 8538122
TI  - [Problems in the accompanying of mother and child. Between competition and
      insecurity].

PMID- 8538123
TI  - [Sudden infant death--position paper].

PMID- 8538124
TI  - ["Debriefing"--a communication model--also useful for hospital teams].

PMID- 8538125
TI  - [Behind the scene of the Swiss Nursing Association at work. Representation of 3
      different interests--a balancing act].

PMID- 8538126
TI  - [No false comfort].

PMID- 8538127
TI  - [Integration of research into care. Better understanding of patients with
      dementia].

PMID- 8538128
TI  - [Nursing care of the diabetic child and the family. "Why do I have this
      disease?"].

PMID- 8538129
TI  - [Community health in the Sultanate of Oman. When progress is too fast...].

PMID- 8538130
TI  - [Women facing their professional future. Did you say career?].

PMID- 8538132
TI  - [How to get rid of harmful behavior. When the spirit is not yet willing...].

PMID- 8538131
TI  - [Home care: the ideal].

PMID- 8538133
TI  - [The burnout syndrome increases during the recession. Burnout, a taboo topic like
      alcoholism].

PMID- 8538134
TI  - [As much jurisprudence as necessary].

PMID- 8538135
TI  - [Standardized prevention of constipation].

PMID- 8538136
TI  - [The problem of refuse in hospitals].

PMID- 8538137
TI  - [Infection statistics--the ideal form of self deception].

PMID- 8538138
TI  - [Potentials of endobronchial Laser therapy].

PMID- 8538139
TI  - ["Children between dreams and trauma"--children's movies in the hospital].

PMID- 8538141
TI  - [The situation of caregivers in home nursing].

PMID- 8538140
TI  - [Gerontological problems in general care].

PMID- 8538142
TI  - [The complete activity is more than just doing it].

PMID- 8538143
TI  - [Ethics. Between dust and the stars].

PMID- 8538144
TI  - [Alternative medicine versus school medicine].

PMID- 8538145
TI  - [Reality and image].

PMID- 8538146
TI  - [Nosocomial staphylococcal infections].

PMID- 8538147
TI  - [Perinatal measles infection enhances the risk of Crohn disease. Epidemiological
      study from Sweden].

PMID- 8538148
TI  - [Factors in the prognosis for premature infants with very low birth weight].

PMID- 8538149
TI  - [After care after surgery for breast cancer. Less is not necessarily worse].

PMID- 8538150
TI  - [Problems of hygiene in the use of breathing gas humidifiers].

PMID- 8538151
TI  - [STANDARD endotracheal suction/tracheostomy].

PMID- 8538152
TI  - [Dietician--the expert in nutrition and dietetics].

PMID- 8538153
TI  - [Infectious diseases in Germany and important vaccinations for adults].

PMID- 8538154
TI  - [Topics that give courage. A reader about last things].

PMID- 8538155
TI  - [Godfather Death].

PMID- 8538156
TI  - Validation of a technique of computer-aided tumor volume determination.
AB  - Tumor volume at diagnosis is an important prognostic factor and volume change may
      predict therapeutic response. However, the accuracy of in vivo tumor volume
      measurement has not been established. The purpose of this study was validation of
      a personal computer-based technique of in vivo volume determination. CT scans of
      8 radiological phantoms and 25 neuroblastoma patients were digitized using three
      dimensional reconstruction and volume determination software. Phantom volumes
      were calculated from known dimensions or direct measurement while tumor volumes
      were determined by water displacement at the time of complete gross resection.
      Comparison to tumor volume determination was performed using an ellipsoid
      geometric model. The standard deviation for computer-generated triplicate volume
      determinations varied from 0.1 to 5.6 cc (median = 0.6 cc). Linear regression
      analysis demonstrated a close correlation between computer-derived volumes and
      the volume measured at surgery (r = 0.99) with small variability. In contrast,
      the correlation coefficient between ellipsoid formula-derived and water
      displacement volumes was 0.93. Computer-generated tumor volume determination is
      reproducible, accurate, and easily obtained from hard copy scans. This technique
      provides a quantitative in vivo measurement for use as a prognostic or
      therapeutic response variable.

PMID- 8538157
TI  - The effect of partial portal decompression on portal blood flow and effective
      hepatic blood flow in man: a prospective study.
AB  - With the advent of transjugular intrahepatic porta-systemic stent shunt and the
      wider application of the surgically placed small diameter prosthetic H-graft
      portacaval shunt (HGPCS), partial portal decompression in the treatment of portal
      hypertension has received increased attention. The clinical results supporting
      the use of partial portal decompression are its low incidence of variceal
      rehemorrhage due to decreased portal pressures and its low rate of hepatic
      failure, possibly due to maintenance of blood flow to the liver. Surprisingly,
      nothing is known about changes in portal hemodynamics and effective hepatic blood
      flow following partial portal decompression. To prospectively evaluate changes in
      portal hemodynamics and effective hepatic blood flow brought about by partial
      portal decompression, the following were determined in seven patients undergoing
      HGPCS: intraoperative pre- and postshunt portal vein pressures and portal vein
      inferior vena cava pressure gradients, intraoperative pre- and postshunt portal
      vein flow, and pre- and postoperative effective hepatic blood flow. With HGPCS,
      portal vein pressures and portal vein-inferior vena cava pressure gradients
      decreased significantly, although portal pressures remained above normal. In
      contrast to the significant decreases in portal pressures, portal vein blood flow
      and effective hepatic blood flow do not decrease significantly. Changes in portal
      vein pressures and portal vein-inferior vena cava pressure gradients are great
      when compared to changes in portal vein flow and effective hepatic blood flow.
      Reduction of portal hypertension with concomitant maintenance of hepatic blood
      flow may explain why hepatic dysfunction is avoided following partial portal
      decompression.

PMID- 8538158
TI  - Octreotide inhibition of serotonin-induced ileal chloride secretion.
AB  - Octreotide (SMS, synthetic miniature somatostatin) effectively alleviates the
      secretory diarrhea of the malignant carcinoid syndrome. Although SMS inhibits
      tumor release of serotonin (5HT) and other bioactive agents, it also inhibits the
      diarrhea in patients who continue to exhibit elevated serum levels of 5HT. This
      observation suggest that SMS may directly inhibit mediator-stimulated intestinal
      ion secretion at the mucosal level. To test this hypothesis, intestinal ion
      secretion was studied in rabbit ileal mucosa mounted in Ussing chambers. Maximal
      changes in short circuit current (delta Isc) were observed as an indicator of
      mucosal ion secretion. The application of pathophysiologic concentrations of 5HT
      (10(-5) M) to the mucosal preps resulted in a delta Isc of 52 +/- 6 microA/cm2.
      This 5HT-stimulated delta Isc was significantly inhibited by serosal furosemide
      (10(-3) M) or use of a chloride-depleted medium, indicating that 5HT stimulates
      electrogenic chloride secretion in the rabbit ileum. Pretreatment with a
      therapeutic concentration of SMS (10(-8) M) resulted in a significant inhibition
      of 5HT-stimulated electrogenic Cl- secretion (9 +/- 1 microA/cm2) (P < 0.005).
      This inhibitory effect of SMS was not seen in tissue pretreated with pertussis
      toxin. The results of these experiments demonstrate that octreotide inhibits 5HT
      stimulated electrogenic chloride secretion at the mucosal level. Additionally
      this inhibitory effect of octreotide is likely mediated by activation of the
      inhibitory subunit of membrane-bound GTP-binding regulatory proteins. These
      results thus provide experimental evidence in support of the ability of SMS to
      ameliorate the carcinoid diarrhea by a direct effect on stimulated mucosal ion
      secretion.

PMID- 8538159
TI  - Electron transport chain activity in normal and activated rat macrophages.
AB  - The pivotal role played by the macrophage in specific and nonspecific immunity
      suggests that the physiological status of the macrophage may effect the overall
      regulation of the host defense system. Many studies have evaluated macrophages as
      effector cells by examining expression of surface markers, cytokine release, or
      tumor killing in the presence of challenge to host defenses. In this report, the
      physiological parameter of mitochondrial respiration in freshly isolated rat
      macrophages is shown to be regulated upon activation in vivo. Assay conditions
      for the reduction of MTT [3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium
      bromide] in rat macrophages were optimized and used to quantitate electron
      transport chain activity as a measure of mitochondrial respiration.
      Corynebacterium parvum administration significantly increased the activity of the
      mitochondrial electron transport chain in both peritoneal (120% increase, 0.18 +/
      .01 vs 0.40 +/- .03, P < 0.01) and liver macrophages (143% increase, 0.12 +/-
      .02 vs 0.30 +/- .06, P < 0.01) as detected by augmented MTT reduction. It is
      demonstrated further that MTT reduction is distinct from the respiratory burst
      activity of macrophages and supports the mitochondrial localization of
      intracellular MTT reduction in this cell type. These results demonstrate that
      electron transport chain activity is a physiological indicator of macrophage
      activation.

PMID- 8538160
TI  - Prevention of tissue injury and postsurgical adhesions by precoating tissues with
      hyaluronic acid solutions.
AB  - The effectiveness of inhibiting serosal tissue damage and preventing surgical
      adhesions by precoating tissues with dilute solutions of hyaluronic acid (HA) was
      evaluated in a rat cecal abrasion model. This study was performed at three
      independent laboratories using the same protocol. Three hundred and seventy-five
      adult rats were divided into five treatment groups (125 animals at each study
      site): 0.1% HA, 0.25% HA, 0.4% HA, phosphate-buffered saline solution (PBS), and
      no solution. The abdominal cavity of each animal was precoated with 4 ml of test
      solution or no solution, prior to a controlled abrasion of the cecum. One week
      later, the animals were sacrificed and adhesions were scored on a 0-4 scale. The
      data were pooled because no statistical difference was found in the trends at the
      three study sites. The PBS precoating and no tissue precoating treatment groups
      had the same high incidence of cecal adhesions, which was significantly higher
      than the incidence of adhesions in the HA treatment groups. As the HA
      concentration in the precoating solution increased from 0% (PBS group) to 0.4%
      HA, the mean incidence of cecal adhesions decreased in a concentration-dependent
      manner from 1.6 +/- 0.11 to 0.7 +/- 0.09 (P < 0.001). The percentage of animals
      with no cecal adhesions increased from 11% in the PBS group to 50% in the 0.4% HA
      treatment group (P < 0.001). In a separate histological study employing 150 rats,
      HA solutions significantly inhibited serosal tissue damage and ameliorated the
      inflammatory response due to abrasion and desiccation compared to that with no
      coating or precoating with buffered saline. Together, these studies demonstrate
      that tissue precoating with dilute HA solutions reduces damage to serosal tissues
      during surgery and thereby limits formation of postsurgical adhesions.

PMID- 8538161
TI  - Endothelial leukocyte adhesion molecule-1-mediated vasoinvasion of human
      pancreatic adenocarcinoma.
AB  - The sialyl Lewis antigens, the ligands of endothelial leukocyte adhesion molecule
      1 (ELAM-1), have been used as important tumor markers for the digestive system.
      The expression of two sialyl Lewis antigens, sialyl Lewis A antigen (SLea) and
      sialyl Lewis X antigen, was examined in human pancreatic cancer cells. The
      expression of SLea was dominant, as shown by flow cytometric analysis.
      Furthermore, suppressive effects of anti-SLea antibody and anti-ELAM-1 antibody
      on human pancreatic cancer cell vasoinvasion were demonstrated using a new assay
      system, the vasoinvasion chamber. These results suggest the critical involvement
      of SLea and ELAM-1 molecules in human pancreatic cancer cell vasoinvasion.

PMID- 8538162
TI  - A new model of intraabdominal abscess: usefulness for hydrosaline metabolism
      studies in parenteral nutrition associated with sepsis.
AB  - The present study was set up to develop a new model of intraabdominal abscess
      (IAA) useful for hydrosaline metabolism studies based on the ligation of the
      appendix (AL) and wrapping of the appendix tip with omentum. Two experiments were
      designed: (1) to characterize the model and (2) to investigate extracellular
      volume (ECV) changes during parenteral nutrition (PN). Four groups of rabbits
      were studied at 3 (3DA) and 7 days (7DA) after AL or sham operation. PN was given
      for 6 days to two groups of septic rabbits: high volume HV) and low volume (LV)
      groups received 100 and 70 ml/kg.day of water with 7 and 0 meq/day of ClNa,
      respectively. Serum albumin (SA), ECV, and weight, water and sodium balances were
      determined. In 3DA, weight loss, reduced spontaneous intake, negative water
      balance, and reduction in SA were noted. Low SA, higher weight loss, and reduced
      intake were still observed in 7DA. SA correlated with ECV (r2 = 0.61, P = 0.003)
      in 7DA. Positive nitrogen balance was achieved during PN. The HV group had higher
      water and sodium balances than LV. In the HV group only, SA negatively correlated
      with sodium balance and with ECV at the end of PN (r2 = 0.87, P = 0.0007 and r2 =
      0.9, P = 0.0001). The impact on hydrosaline metabolism of IAA in this model
      resembles that of moderate sepsis in humans. SA decrease appears to have two
      major components: escape around the inflammatory area and dilution. ECV expansion
      after PN is influenced by the initial SA concentration.

PMID- 8538163
TI  - The anoxic fibroblast response is an early-stage wound healing program.
AB  - When fibroblasts experience anoxia, a cellular program is initiated which results
      in stepwise activation of an endogenous SVL30 retroelement, metabolic adaptation
      to reliance on glycolysis, protease secretion, and endonuclease induction. This
      response is reversible and occurs with no reduction in cellular viability.
      Examination of experimental wounds reveals that this same response is
      physiologically activated during the early phase of wound healing when near
      anoxic conditions prevail and wound debridement predominates. Procathepsin D has
      been identified as one of three major anoxia-inducible secretory proteins; its
      secretion is the result of altered routing within the cell, with no apparent
      change in the amount of the protein synthesized. A delayed cellular contractile
      response occurs approximately 1 week after fibroblasts experience as little as 16
      hr of anoxia; this response appears to contribute to wound contraction.

PMID- 8538164
TI  - Antiproliferative effects of tyrosine kinase inhibitors (tyrphostins) on human
      bladder and renal carcinoma cells.
AB  - Growth factor receptors with tyrosine kinase activity mediate paracrine and
      autocrine growth regulation of normal and malignant cells. The epidermal growth
      factor receptor (EGF-R) is a tyrosine kinase transmembrane protein that is
      overexpressed by many epithelial malignancies, including transitional cell and
      renal cell carcinoma. Ligand-induced stimulation of cell growth depends on
      activation of the tyrosine kinase activity of the EGF-R. Tyrphostins are small
      molecular weight compounds that have been shown to preferentially inhibit the EGF
      R tyrosine kinase and thus may inhibit EGF-R-dependent cell growth. We examined
      the effect of two tyrphostins, RG14620 and AG555, on the proliferation of three
      transitional cell carcinoma lines (RT4, J82, and T24) and three renal cell
      carcinoma lines (A-198, Caki-1, and Caki-2). Both tyrphostins inhibited
      proliferation of all six cell lines in a dose-dependent fashion. They were
      equally effective with IC50s ranging between 3 and 16 microM. Complete inhibition
      of growth was achieved at tyrphostin concentrations between 10 and 30 microM.
      Although both tyrphostins inhibited proliferation of T24 transitional carcinoma
      cells in growth assays, only RG14620 but not AG555 was found to specifically
      inhibit EGF-R autophosphorylation in this cell line. These results suggest that
      other intracellular targets in addition to the EGF-R are affected by these
      agents. In summary, tyrphostins are potent growth inhibitors for urological
      malignancies.

PMID- 8538165
TI  - Cholinergic agents modulate transport in the isolated, perfused ileum.
AB  - The mammalian small intestine is extensively innervated by cholinergic nerve
      fibers, including projections to the muscular and submucosal layers. This study
      tested the hypothesis that cholinergic agents modulate ileal transport
      independent of alterations in intestinal vascular resistance and motility. Ten
      centimeter segments of rabbit ileum (n = 32) were vascularly perfused ex vivo
      with a physiologic electrolyte solution containing red cells. The lumen was
      perfused with an electrolyte solution containing [14C]polyethylene glycol. Net
      fluxes of water, sodium, and chloride were calculated during three 20-min
      periods: basal, drug infusion, and recovery. Agents infused at a final arterial
      concentration of 10(-5) mole/liter included acetylcholine, atropine, and
      hexamethonium. Measured perfusion pressure reflected changes in vascular
      resistance. Recovery calculations controlled for motility effects. Acetylcholine
      caused significant secretion of water, sodium, and chloride (P < 0.05). The
      infusion of atropine or hexamethonium alone had no effect. Atropine but not
      hexamethonium prevented the prosecretory effect of acetylcholine. There were no
      significant changes in perfusion pressure or 14C recovery for any infused agent.
      Acetylcholine-induced ileal secretion is (1) mediated via atropine-sensitive
      muscarinic cholinergic receptors, (2) independent of extraintestinal neural
      pathways, and (3) independent of changes in vascular resistance or motility.
      These data support the hypothesis that acetylcholine influences ileal transport
      directly, independent of alterations in vascular resistance and motility.

PMID- 8538166
TI  - Up-regulation of TNF alpha mRNA in the rat spleen following induction of acute
      pancreatitis.
AB  - Tumor necrosis factor-alpha (TNF alpha) is postulated to be a mediator of the
      systemic complications associated with acute pancreatitis. Neutralization of TNF
      alpha with monoclonal antibody ameliorates the morbidity and mortality associated
      with acute pancreatitis in a rat model. Although high levels of TNF alpha are
      measurable in peripheral blood in acute pancreatitis, specific sites of TNF alpha
      production in this disease have not been described. In this study we show that
      induction of pancreatitis causes up-regulation of TNF alpha messenger RNA (mRNA)
      at a distant organ site, the spleen. Hemisplenectomies were performed in male
      Sprague-Dawley rats prior to induction of pancreatitis by pancreatic duct
      infusion of artificial bile. Completion hemisplenectomies were then performed at
      30 min, 1 hr, and 2 hr after pancreatitis induction. Quantitation of TNF alpha
      mRNA in the hemispleens before and after pancreatitis using a semiquantitative
      reverse transcriptase-polymerase chain reaction method revealed an 80-fold
      increase in amount of TNF alpha mRNA by 2 hr after induction of pancreatitis. By
      contrast, control rats receiving a sham operation showed no significant increase
      in TNF alpha mRNA expression after infusion of the pancreatic duct with saline.
      The increase in TNF alpha mRNA production was associated with increased serum TNF
      alpha product levels and was independent of endotoxin. We conclude that severe
      acute pancreatitis in the rat model is associated with significant up-regulation
      of TNF alpha mRNA in splenic mononuclear cells. These data provide evidence that
      the local events of acute pancreatitis can induce up-regulation of TNF alpha mRNA
      at a distant site and suggest a possible mechanism of pathogenesis of the
      systemic manifestations of this disease.

PMID- 8538167
TI  - Glutathione-mediated preservation and enhancement of isolated perifused islet
      function.
AB  - It has been shown that myocardial tissue function may be better preserved if
      antioxidants are incorporated into the reoxygenation medium at the end of the
      ischemic period following isolation of the organ. Although isolated pancreatic
      islets are prone to ischemic-reperfusion injury, it is not clear if antioxidants
      have a role in the preservation of their function. The purpose of the present
      study, therefore, was to examine the effect of the addition of glutathione (GSH)
      to a physiologic incubation medium on pancreatic islet response to glucose
      stimulation. Islets isolated by microdissection were preperifused at the rate of
      1 ml/min for 1 hr at 37 degrees C, with Krebs-Ringer bicarbonate (KRB) buffer
      containing 1% albumin, 5.5 mM (basal) glucose without (control) or with 10 mM
      glutamine or 10 mN GSH and maintained at pH 7.4 by continuous gassing with 95/5%
      O2/CO2. After preperifusion, basal effluent samples were taken on ice for 20 min.
      The perifusion was then continued for 20 min with the KRB containing 27.7 mM
      glucose alone, followed by another 20 min of basal glucose washout. Solutions
      were changed using a stopcock and all effluent perifusate samples obtained were
      stored frozen at -20 degrees C until radioimmunoassay for insulin. Total insulin
      output in the control group increased from a basal 11.45 +/- 3.18 to 29.23 +/-
      7.08 ng/6 islets/20 min (P < 0.001, n = 5) when the glucose concentration was
      raised to 27.7 mM. During a 20-min washout, insulin secretion was still
      significantly raised and did not return to the prestimulation basal rate. In the
      glutamine-treated islets, insulin output increased from 7.23 +/- 0.94 to 16.83 +/
      2.25 ng/6 islets/20 min (P < 0.001, n = 5) with 27.7 mM glucose stimulation and
      the significantly raised washout basal rate of secretion did not return to the
      prestimulation level. GSH treatment not only caused an enhanced 27.7 mM glucose
      stimulation (8.46 +/- 1.99 to 38.72 +/- 11.51 ng/6 islets/20 min, P < 0.001, n =
      6) of insulin output but also completely restored the basal rate of insulin
      secretion to the prestimulation level within the 20-min washout perifusion. In
      conclusion, these data show that incubation of isolated islets with GSH enhanced
      their secretory response to glucose stimulation and preserved their functional
      integrity.

PMID- 8538168
TI  - The effect of interleukin-1 beta or transforming growth factor-beta on radiation
      impaired murine skin wound healing.
AB  - The ability of exogenous interleukin-1 beta (IL-1 beta) or transforming growth
      factor-beta (TGF-beta) to reverse radiation-induced defective wound healing was
      investigated. Mice were irradiated with 8.5 or 11 Gy to total body (TB), 12 or 16
      Gy to hemibody (HB), or 20 or 26 Gy to skin alone immediately prior to surgical
      wounding in order to determine the effect of hematopoietic system depletion on
      cytokine action. A single dose of IL-1 beta or TGF-beta or vehicle control was
      applied to each wound. All radiation doses and types resulted in a deficit in
      wound healing when measured on Days 11 and 14. IL-1 beta enhanced wound tensile
      strength (WTS) in TB-irradiated mice, while TGF-beta enhanced WTS in HB
      irradiated mice. Neither cytokine was effective at enhancing WTS in unirradiated
      or skin-only irradiated animals. In addition IL-1 beta and TGF-beta showed
      distinct differences in their effects on the kinetics of healing with time after
      wounding. The effects of TGF-beta appeared to be transient with compromise of the
      gain in WTS. The differences in the effects of these two cytokines in affecting
      wound healing reflect their involvement in different cellular events in the wound
      healing process.

PMID- 8538169
TI  - Hydration, not silicone, modulates the effects of keratinocytes on fibroblasts.
AB  - Topical silicone gel or silicone cream with occlusive dressing has proved to be
      an efficacious method for the treatment and prevention of hypertrophic scars and
      keloids, but how this action is triggered remains unknown. Hydration of the
      epidermis and/or the cellular effects of the released low-molecular-weight
      silicone oil have been suggested as possible mechanisms. In order to further
      elucidate the mechanism, we used an in vitro keratinocyte-fibroblast coculture
      model to investigate the cellular effects of silicone and hydration. In this
      model, the condition of clinical usage of topical silicone gel or cream or the
      condition of hydration exerted by occlusive dressing could be mimicked. The model
      consisted of two chambers separated by a semipermeable membrane, in which a fully
      differentiated stratified epithelium is present in the upper chamber and medium
      and monolayer fibroblasts are located in the lower chamber. The keratinocytes
      were nourished from the basal side only, while the apical surface was submerged
      in silicone oil, paraffin, Hanks' balanced salt solution, or medium (hydration);
      or it was exposed to air (control). In the hydration-treated group, the
      proliferation of fibroblasts measured as [3H]thymidine incorporation and their
      collagen, glycosaminoglycan production was significantly inhibited when compared
      with the controls, but exposure of the keratinocyters to silicone oil or paraffin
      did not influence fibroblast behavior. The results suggest that hydration, not
      silicone, modulates the in vitro keratinocyte-fibroblast interaction. This may be
      one possible mechanism by which topical silicone or occlusive dressing treatment
      may affect the development of hypertrophic scars and keloids.

PMID- 8538170
TI  - Mechanisms of reoxygenation-induced calcium overload in cardiac myocytes:
      dependence on pHi.
AB  - This study investigated the selective effects of intracellular (pHi) or
      extracellular change in pH on reoxygenation-induced Ca2+ overload in simulated
      myocardial hypoxia. Experiments were performed in cultured cardiomyocytes
      isolated from the ventricle of neonatal ICR mouse. A model of chemical hypoxia
      with 2 mM sodium cyanide was developed to mimic the ATP depletion of hypoxia.
      This chemical hypoxia was "reoxygenated" and the dynamics in intracellular Ca2+
      concentration ([Ca2+]i) and pHi were monitored using the fluorescent dyes fura-2
      and 2', 7'-bis (2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. During a
      40-min chemical hypoxia, pHi progressively fell from 7.2 to 6.6. Reoxygenation
      with control solution caused rapid recovery of pHi and a marked increase in
      [Ca2+]i (1884 +/- 136 nM). Intracellular acidotic reoxygenation produced by
      lactate apparently prolonged the time course of pHi recovery and significantly
      suppressed reoxygenation-induced Ca2+ overload (1170 +/- 118 nM, P = 0.008).
      Extracellular acidotic reoxygenation with 2-(N-morpholino) ethanesulfonic acid
      (pK = 5.96) buffer somewhat suppressed the Ca2+ overload; however, the maximal
      value of [Ca2+]i was not reduced significantly compared with the control (1790 +/
      122 nM, P = 0.130). In addition, inhibition of Na(+)-H+ exchange by amiloride
      potentiated prolongation of intracellular acidosis during reoxygenation and
      resulted in a minimal increase in [Ca2+]i (985 +/- 102 nM, P = 0.004). These
      results suggest that reoxygenation-induced Ca2+ overload is closely correlated
      with intracellular pH in the initial phase of reoxygenation, and the protective
      effects of extracellular acidosis is principally mediated by intracellular
      acidification of reoxygenated cardiomyocytes.

PMID- 8538171
TI  - Transforming growth factor-beta 1 serves as an autocrine inhibitor of human
      endothelial cell/lymphocyte adhesion.
AB  - Other investigators have shown that exogenously administered transforming growth
      factor-beta (TGF-beta) inhibits lymphocyte adherence to vascular endothelial
      cells (VEC). We examined the role of TGF-beta 1 as an autocrine mediator of
      lymphocyte adhesion to adult human VECs. VECs were harvested from eight saphenous
      or cadaveric iliac veins using 0.2% collagenase. Low-passage VECs in MCDB + 0.1%
      BSA were pretreated for 24 hr with monoclonal anti-TGF-beta 1 antibody (5
      micrograms/ml), LPS (5 micrograms/ml), or IL-1 (10 U/ml). Adherence of
      fluorescently labeled lymphocytes to pretreated VECs was quantitated and results
      were expressed as relative adhesion compared to untreated control. Total mRNA
      from LPS- or IL-1-treated VECs was subjected to Northern analysis to determine
      relative TGF-beta 1 expression. Total TGF-beta 1 protein concentration in
      supernatants from LPS- or IL-1-treated VECs was determined by ELISA. Data (means
      +/- SEM) were analyzed by ANOVA with a Newman-Keuls posttest. Neutralizing
      endogenous TGF-beta 1 with anti-TGF-beta 1 antibody significantly increased
      adhesion of lymphocytes to VEC monolayers compared to control (125 +/- 3 vs 101
      +/- 2%, P < 0.01, n = 8). The level of adhesion was equivalent to that seen with
      IL-1 stimulation (131 +/- 6%). Spearman correlation of lymphocyte adherence to IL
      1- or LPS-treated VECs vs TGF-beta 1 mRNA expression or vs relative TGF-beta 1
      protein concentration showed significant inverse relationships (r = -0.82, P <
      0.001, and r = -0.87, P < 0.001, respectively). Endogenous TGF-beta 1's
      inhibitory effect on lymphocyte adhesion was blocked by a specific neutralizing
      antibody. VEC TGF-beta 1 mRNA expression and TGF-beta 1 production were inversely
      proportional to lymphocyte adhesion, suggesting down-regulation of TGF-beta 1 in
      response to proinflammatory cytokines. Together, these observations support the
      hypothesis that TGF-beta 1 has an autocrine inhibitory role in regulation of
      lymphocyte adhesion to VECs.

PMID- 8538172
TI  - A model for recording the microcirculatory changes associated with standardized
      electrical injury of skeletal muscle.
AB  - The rate of major limb amputation following high voltage electrical injury
      remains high despite a decrease in mortality rate. Several theories about the
      pathophysiology of electrical injury have been discussed in the literature and
      different clinical regimens have been attempted to decrease the high amputation
      rate. However, to date, the overall tissue response after electrical injury
      remains incompletely understood with nothing new to offer these unfortunate
      patients. We have developed a rat gracilis muscle intravital microscopy
      preparation in order to better understand the mechanisms of this injury. A
      standardized 40-V stimulation of 10-sec duration was applied to the anterior
      belly of the gracilis muscle which translated into a current load of 30 mA. The
      current density was 750 mA/cm2. Sequential intravital assessment of
      microcirculatory changes before injury, as well as 5, 15, 30, 60, 120, 180 and
      240 min after injury was performed. Consistent findings included initial
      cessation of blood flow in many capillary beds, focal flow reversal, venous and
      arterial vascular spasm. Restitution of microvascular flow varied from several
      minutes to 1 hr and was preceded by vasodilation at 5-15 min following the injury
      (+16.9 microns from baseline at 15 min). Starting at 30 min progressive
      vasoconstriction was noted (-0.8 micron from baseline at 30 min, -31.3 microns
      from baseline at 4 hr). High resolution observation of neutrophil behavior showed
      an increase in the number of these cells adherent to venular endothelium in areas
      exhibiting circulatory disturbances (+11.4 cells at 5 min, +15 cells at 4 hr).
      The standardization of this model allows a quantitative method of evaluating the
      microcirculatory changes associated with electrical injury and of studying ways
      to prevent tissue damage. The microcirculatory changes induced by electrical
      injury were similar to those reported in ischemia-reperfusion injury of skeletal
      muscle.

PMID- 8538173
TI  - Superoxide dismutase attenuates effects of platelet-activating factor on gastric
      microcirculation.
AB  - This study examined the effect of Cu-Zn superoxide dismutase (SOD) on platelet
      activating factor (PAF)-induced alterations of the gastric microcirculation. In
      separate experiments using an ex vivo canine gastric segment, changes in vascular
      resistance, filtration, and circulating neutrophil counts were measured during
      intra-arterial infusion of PAF (0.12 to 150 nM, n = 6) alone and with SOD (10
      U/ml, n = 5). PAF produced dose-related increases in vascular resistance and
      filtration. SOD pretreatment attenuated changes in these measurements in response
      to 9 and 38 nM PAF. PAF also produced dose-related increases in the difference
      between arterial and venous neutrophil counts across the gastric segment. SOD
      significantly reduced this neutrophil flux at 0.5, 2, 9, and 38 nM PAF. Our
      results suggest that PAF causes both mucosal ischemia due to increased vascular
      resistance and microvascular injury as evidenced by increased filtration, as well
      as enhanced neutrophil adhesion to the microvasculature. The protective effects
      of SOD suggest that these responses to PAF involve the generation of oxygen
      derived free radicals. In addition, these responses to PAF appear to be dependent
      upon circulating neutrophils.

PMID- 8538174
TI  - Platelet-derived growth factor and wound contraction in the rat.
AB  - This experiment was undertaken for three purposes: (1) to determine a dose
      response curve of acute steroid inhibition of wound contraction in the rat; (2)
      to confirm the results of our preliminary study that platelet-derived growth
      factor (PDGF) enhanced wound contraction in acutely steroid impaired rats; and
      (3) to examine the histology of the PDGF-treated wounds. To determine the dose
      response of acute steroid inhibition of wound contraction, the rats were
      suppressed with daily doses of methylprednisolone and wound contraction was
      measured. Results demonstrated that significant glucocorticoid-induced inhibition
      of wound contraction begins with daily methylprednisolone doses of 2.0
      mg/wound/day or 6.7 mg/kg/day. In an effort to confirm the results of our
      previous study of the effect of PDGF on wound contraction in acutely steroid
      impaired rats and to study the histology of the PDGF-treated wounds, rats were
      suppressed with methylprednisolone or hydrocortisone and administered daily
      topical doses of rPDGF-BB. Wound contraction measurements revealed no improvement
      in the amount or rate of wound contraction. Histologically, the wounds were all
      very similar in the patterns of cellularity, granulation tissue maturity,
      collagen content, and epithelial migration. We have clarified the dose response
      of acute steroid inhibition of wound contraction in rats, data previously
      unavailable, and have concluded that PDGF in reasonable doses does not improve
      wound contraction in steroid-impaired rats nor does it alter the histology of the
      wounds.

PMID- 8538175
TI  - Somatostatin inhibits cholecystokinin-induced contraction of isolated gallbladder
      smooth muscle cells.
AB  - A close relation between the hyperhormonism of somatostatin and gallstone disease
      suggested to us the hypothesis that somatostatin inhibits cholecystokinin (CCK)
      induced gallbladder contraction on the level of target organs. To investigate
      this hypothesis, smooth muscle cells were isolated from human and canine
      gallbladders and the direct inhibitory effects of somatostatin on the CCK-induced
      cell contraction were examined in vitro. Somatostatin alone had no effect on the
      cell motility, while it significantly inhibited the cholecystokinin-octapeptide
      (10(-10) M)-induced cell contraction at the concentration of 10(-6) M (P < 0.01)
      in both human and canine gallbladders. The results demonstrate for the first time
      that somatostatin has a direct inhibitory action against cholecystokinin-induced
      gallbladder contraction. This may partly account for the high frequency of
      gallstone disease in patients with somatostatinoma.

PMID- 8538176
TI  - Eicosapentanoic acid reduces the intimal thickening of autogenous vein grafts and
      enhances endothelium-derived relaxing factor.
AB  - The present study examined the effect of purified eicosapentanoic acid (EPA) on
      intimal thickening of an autogenous vein graft. In addition, experiments were
      performed to determine whether EPA supplementation would alter the endothelium
      dependent responses of the reversed vein graft. Segments of femoral veins were
      grafted into the femoral arteries of dogs. Six dogs received regular chow
      (control group) and six other dogs regular chow with 1500 mg/day 90.0% pure EPA
      (EPA group). At 6 weeks after surgery, the vein grafts were removed from the
      dogs, cut into rings, and suspended in organ chambers for isometric tension
      recording. In some rings, the endothelial cells were removed. When the rings
      taken from the control group were contracted with norepinephrine, adenosine
      diphosphate (ADP) and A23187 caused endothelium-dependent relaxations. In the EPA
      group, the endothelium-dependent responses to ADP were significantly augmented,
      while A23187 caused comparable endothelium-dependent relaxations. Direct
      relaxation in response to sodium nitroprusside was comparable between the two
      groups. Intimal thickening of the grafts in the control group (29.0 +/- 1.8
      microns) was significantly (P < 0.05) greater than in the EPA group (12.5 +/- 1.8
      microns). These results suggest that EPA enhances the release of endothelium
      derived relaxing factor in autogenous vein grafts. This may be one of the effects
      of EPA in reducing the intimal thickening of autogenous vein grafts.

PMID- 8538177
TI  - Alterations of remnant liver carnitine palmitoyltransferase I activity and serum
      carnitine concentration after partial hepatectomy in rats.
AB  - Many authors agree that alteration of the energy substrate from glucose to free
      fatty acid occurs during the early stage after partial hepatectomy. An
      accelerative effect of carnitine on the early phase of liver regeneration was
      suggested in several reports, but much controversy prevails. Using male Wistar
      rats weighing about 200 g as subjects, we undertook partial hepatectomy with
      resection of the median and left lateral lobes (67%). Another group of rats
      undergoing a sham operation was compared. Rats were killed at 6, 24, 48, or 72 hr
      after the operation. The rate of synthesis of DNA and content of DNA in remnant
      liver were chosen as regenerative indicators. Serum carnitine, free fatty acid
      and its metabolites, remnant liver carnitine palmitoyltransferase I (CPT-I)
      activity, high-energy phosphate (HEP), including adenosine triphosphate (ATP),
      and creatine phosphate (CP) were measured. The results showed a marked decrease
      of HEP, ATP, and CP with suddenly increased free fatty acid and total ketone body
      in serum that occurred during the early regenerating phase after partial
      hepatectomy. Serum L-carnitine also increased markedly in this early stage. The
      mitochondrial CPT-I activity in the remnant liver decreased significantly 24 hr
      after partial hepatectomy. Our data show that regenerating liver utilizes free
      fatty acids as an immediate main substrate. Mitochondrial respiration with a CPT
      I effect could be an important reaction in this utilization.

PMID- 8538178
TI  - Local release of fibrinolytic agents for adhesion prevention.
AB  - Tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and
      streptokinase were evaluated for their ability to reduce postsurgical adhesion
      formation in a rat uterine horn devascularization and serosal injury model in a
      blinded, randomized study. Small doses of tPA, uPA, or streptokinase were
      delivered over approximately a 4-day period either from a biodegradable hydrogel
      matrix or as four daily intraperitoneal injections. The hydrogel was formed upon
      the uterine horns by photopolymerization of an aqueous precursor solution
      containing dissolved drug. A control group that received no treatment had an
      average extent of adhesion formation of 72 +/- 15% (mean +/- SEM, percentage of
      the length of the uterine horns involved in adhesions). Application of this
      formulation of the hydrogel alone reduced the extent of adhesion formation to 22
      +/- 10% by functioning as a mechanical barrier. When tPA was released from the
      hydrogel, adhesion formation was reduced to 4 +/- 3%, while when tPA was given by
      intraperitoneal injection, adhesion formation was only reduced to 49 +/- 8%.
      Local delivery of urokinase reduced adhesion formation to 6 +/- 6%, but
      intraperitoneal injection of urokinase did not reduce adhesion formation.
      Streptokinase did not reduce adhesion formation when administered by
      intraperitoneal injection and increased adhesion formation to 45 +/- 9% when
      locally released relative to the hydrogel alone. These results suggest that both
      tPA and uPA may be used to prevent adhesion formation when delivered locally.

PMID- 8538179
TI  - Prevention of postoperative adhesions by single intraperitoneal medication.
AB  - Postoperative adhesions account for a significant morbidity after abdominal,
      gynecological, or cardiac surgery. A large number of compounds have been
      suggested to prevent such adhesions, but none is generally accepted. We have
      compared eight different substances that could be beneficial for the prevention
      of postoperative adhesions in a new standardized rabbit model with measurement of
      the areas of adhesion. In 10 groups of 20 rabbits an area of abrasion of the
      serosa of the ileum, the appendix, and the abdominal wall measuring 10,000 mm2
      was created by an emery piston during celiotomy. The controls received no
      medication. The treatment groups received a single intraperitoneal administration
      of 1 ml per 100 g body wt of normal saline (NaCl), 5 mg taurolidine (T), 0.5 U
      plasmin/300 U DNase (PD), 2000 IU streptokinase/500 IU streptodornase (SS), 7 mg
      phosphatidylcholine (PC), 4 mg hyaluronic acid (HA), 7 mg sphingolipid (SL), 7 mg
      galactolipid (GL), or 0.5 ml tetrachlorodecaoxide (TCDO), respectively. Ten days
      later the extent of adhesions was quantified by morphometry. The total area of
      adhesions (+/- SEM) was found to be 1998 +/- 124 mm2 in controls. The application
      of NaCl reduced the adhesions to 1368 +/- 58 mm2, of T to 1012 +/- 48 mm2, of PD
      to 673 +/- 33 mm2, of SS to 360 +/- 44 mm2, of PC to 335 +/- 84 mm2, of HA to 328
      +/- 76 mm2, of SL to 278 +/- 80 mm2, of GL to 261 +/- 67 mm2, and of TCDO to 240
      +/- 45 mm2. The effects of PD, SS, PC, HA, SL, GL, and TCDO were significant in
      comparison to controls and NaCl. Our experimental data suggest that the two new
      lipid substances, SL and GL, are the most likely candidates for routine clinical
      use in the prevention of postsurgical adhesions.

PMID- 8538180
TI  - Role of endogenous nitric oxide in ischemia-reperfusion injury in rat liver.
AB  - Evidence has accumulated that oxygen-derived free radicals contribute to the
      cellular damage induced by ischemia-reperfusion. It has been suggested that
      nitric oxide (NO) may act as a protective factor in ischemia-reperfusion injury
      since NO increases blood flow and may scavenge oxyradicals. Nevertheless,
      controversy exists as to the role of NO. This study was designed to clarify the
      role of endogenous NO in ischemia-reperfusion-induced liver injury in rats in
      vivo. Wistar rats weighing 250-300 g were divided into three groups: (1)
      untreated group (Control); (2) NG-nitro-L-arginine, a specific inhibitor of NO
      production (L-NNA); and (3) L-arginine-pretreated L-NNA group (AR+L-NNA).
      Occlusion of all vessels to the median and left hepatic lobes (60 min) was
      followed by reperfusion for 1 or 24 hr. L-NNA was administered before ischemia as
      a 10 mg/kg bolus. L-Arginine was given just before L-NNA administration as a 100
      mg/kg bolus. Administration of L-NNA resulted in endothelial cell injury
      characterized by the elevation of serum hyaluronic acid as well as the reduction
      of hepatic tissue blood flow, and the recovery of hepatic adenosine triphosphate
      was depressed compared with the control after both 1 and 24 hr of reperfusion.
      Furthermore, the leakages of various liver enzymes and lipid peroxide were also
      increased, associated with histological damage. This effect of L-NNA was
      completely abolished by pretreatment with L-arginine. These results suggest that
      endogenous NO provides a protective effect against ischemia-reperfusion injury in
      rat liver.

PMID- 8538181
TI  - Mild hypothermia protects against irreversible damage during prolonged spinal
      cord ischemia.
AB  - Mild hypothermia to 32 degrees C protected the spinal cords of 5 rabbits
      subjected to 90 min of surgically created spinal cord ischemia. Spinal cord
      ischemia was produced in 10 New Zealand White rabbits by transection of four out
      of the five segmental arteries arising from the abdominal aorta below the renal
      arteries plus 90-min occlusion of the remaining segmental artery 24 hr later. Of
      these 10 rabbits, 5 served as controls. Recovery, or failure to recover, as
      assessed by examining the rabbits for permanent loss of sensory and motor
      function in the hind limbs, was compared in the two groups. The duration of the
      ischemia was sufficient to lead to a total or near total loss of sensory and
      motor function in all control rabbits. These results may have implications for
      the care of patients subjected to spinal cord ischemia.

PMID- 8538182
TI  - Mixed-function oxidase activity in sepsis.
AB  - Hepatic dysfunction is a major contributor to death in multiple organ system
      failure. To evaluate whether this dysfunction increases with the length of
      sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on
      mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid
      peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr,
      homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was
      determined by assay and P450 activity was determined by the metabolism of
      ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring
      malondialdehyde content. Septic rats showed decreases in P450 levels and
      activity, which worsened with duration of sepsis. These decreases were partially
      lessened by hyperoxia. Although there was a trend toward increased lipid
      peroxidation, this effect was not statistically significant. This study suggests
      that while MFO content and activity decrease with sepsis, these decreases do not
      appear to be related to the production of oxygen-derived free radicals.
      Furthermore, hyperoxia actually appears to have a protective role in this
      instance.

PMID- 8538183
TI  - Retinoids and chemoprevention: clinical and basic studies.
AB  - Retinoids, which include natural vitamin A (retinol) and its esters and synthetic
      analogues, are the best-studied class of agents in chemoprevention. There are
      more than 4,000 different retinoids which have a wide spectrum of preclinical
      activities, structures, pharmacological profiles, tissue distributions, receptor
      specificities, and toxicities. A number of retinoids have significant activity in
      many in vivo experimental systems including skin, bladder, lung, breast and oral
      carcinogenesis. In clinical trials, several retinoids have achieved significant
      activity in the reversal of head and neck, skin, and cervical premalignancy, and
      in the prevention of second primary tumors associated with head and neck, skin,
      and non-small cell lung cancer. Since 1984, our group has conducted a series of
      clinical trials to explore the chemopreventive potential of 13-cis-retinoic acid
      (13cRA) in the aerodigestive tract. We have conducted two consecutive randomized
      studies in subjects with premalignant lesions of the oral cavity. These studies
      showed that high-dose 13cRA alone can achieve significant short-term reversal of
      oral premalignancy, and that high-dose followed by low-dose 13cRA can maintain
      suppression of oral carcinogenesis. Three other randomized trials have confirmed
      significant retinoid activity in this human carcinogenic system. We also
      developed a randomized, placebo-controlled trial of adjuvant high-dose 13cRA in
      patients with head and neck cancer. Second primary tumor development was
      significantly decreased in the 13cRA group, but 13cRA had no impact on primary
      disease recurrence or survival. This presentation will update the current status
      of clinical trials and correlative laboratory studies of potential intermediate
      endpoint biomarkers in retinoid chemoprevention of aerodigestive tract
      carcinogenesis.

PMID- 8538184
TI  - Cancer Chemopreventive Agents: Drug Development Status and Future Prospects.
      Conference proceedings. Princeton, New Jersey, October 18-22, 1994.

PMID- 8538185
TI  - Oltipraz: clinical opportunities for cancer chemoprevention. p.
AB  - Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], originally developed
      as an antischistosomal agent, protects against chemical carcinogenesis in lung,
      trachea, forestomach, small intestine, colon, breast, skin, liver and urinary
      bladder in rodents. Oltipraz induces electrophile detoxication enzymes, resulting
      in diminished carcinogen-DNA adduct formation and reduced cytotoxicity, an
      important component of anticarcinogenic actions. Phase I trials of this drug have
      been recently conducted in the United States and indicate that the maximum
      tolerated dose is about 125 mg/day over a six-month period. Grade I/II dose
      limiting toxicities included photosensitivity/heat intolerance, gastrointestinal,
      and neurologic toxicities. Ongoing studies are monitoring relationships between
      dose scheduling, drug plasma concentrations and pharmacodynamic action.
      Subsequent trials with this agent might most appropriately target individuals at
      high risk for occupational or environmental exposures to genotoxic carcinogens.
      Towards this end, a randomized, placebo-controlled Phase II study is planned for
      people at high risk for exposure to aflatoxins and development of hepatocellular
      carcinoma. Modulation of biomarkers reflecting the biologically effective dose of
      aflatoxin will serve as study endpoints.

PMID- 8538186
TI  - Effects of oltipraz and related chemoprevention compounds on gene expression in
      rat liver.
AB  - One promising approach to cancer chemoprevention involves the induction of phase
      II xenobiotic metabolism enzymes. Since this approach requires drugs specifically
      intended to alter tissue gene expression patterns over long periods, it will be
      important to determine experimentally which proteins are increased or decreased
      by treatment, and how such alterations may (or may not) be related to the
      postulated chemopreventive mechanism. We have employed two-dimensional
      electrophoresis to detect and quantitate gene expression effects of candidate
      chemoprevention compounds in the livers of treated rats. Oltipraz, an inducer of
      several phase II enzymes, affected a series of at least 26 proteins, most of
      which were slightly decreased by treatment. Several proteins were increased, the
      prime example being rat liver spot 693, which was induced more than 7-fold by
      oltipraz. This protein was excised from multiple 2-D gels and subjected to in
      situ tryptic digestion followed by microchemical sequence analysis. The resulting
      multiple peptide sequences match perfectly with the cDNA-derived sequence of rat
      aflatoxin B1 aldehyde reductase (AFAR). Using quantitative measurements of AFAR
      from 2-D gels, we compared a series of dose regimens. Oltipraz administration by
      gavage or in diet appeared equally effective, while recovery studies indicated a
      half-time of 5.5 days for disappearance of the AFAR protein.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8538187
TI  - Controlled clinical trials with fenretinide in breast cancer, basal cell
      carcinoma and oral leukoplakia.
AB  - We are conducting three randomized studies (breast cancer, basal cell carcinoma,
      oral leukoplakia) and report our methodological approach and accrual here. The
      aim of the breast cancer study is prevention of a contralateral primary lesion in
      women already treated for breast cancer; the aim of the basal cell carcinoma
      study is prevention of recurrences or new occurrence after surgical resection;
      and the aim of the oral leukoplakia study is prevention of recurrences and new
      occurrence after CO2 laser resection. The studies were planned according to a
      randomized design with an intervention arm vs a no-treatment arm. Patients in the
      intervention group receive 4-HPR at a dose of 200 mg po. The duration of
      treatment is five years in the breast cancer study, and one year in the basal
      cell carcinoma and oral leukoplakia studies. The breast cancer study started in
      March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered
      the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the
      control group). Of 2,849 evaluable patients, 867 completed the first five years,
      1,142 are still ongoing, and 840 patients have interrupted the study for various
      reasons. Follow-up is ongoing. The basal cell carcinoma study started in January
      1990. As of January 1994, a total of 786 patients had entered the study; 760 were
      evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients
      in the study, 568 completed the first year, 62 are ongoing and 130 discontinued
      for various reasons. The study is ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538188
TI  - Oltipraz, a novel inhibitor of human immunodeficiency virus type 1 (HIV-1)
      replication.
AB  - Glutathione (GSH) levels are markedly depleted in patients infected with human
      immunodeficiency virus type 1 (HIV-1) and supplementation of media with high
      concentrations (5-20 mM) of low-molecular weight thiols prevents HIV-1
      replication in cultured cells. We were intrigued whether chemopreventive enzyme
      inducers might represent a more pharmacologically feasible method to inhibit HIV
      1 replication since these compounds elevate intracellular concentrations of GSH
      at nontoxic doses in vivo. After establishing that all inducers surveyed were
      able to elevate GSH levels in human T-cell and monocytoid cell lines, we were
      surprised to find that oltipraz (5-pyrazinyl-4-methyl-1,2-dithiole-3-thione) was
      uniquely able to inhibit HIV-1 replication (IC50 = 5-15 microM). Oltipraz and
      other antiviral 1,2-dithiole-3-thiones (DTTs) appear to inhibit acute HIV-1
      replication by inactivating reverse transcriptase (RT). However, among DTTs that
      inhibit HIV-1 replication in acutely infected cells, only oltipraz was able to
      inhibit HIV-1 replication in a chronic infection model. Thus, in addition to
      inactivating RT, oltipraz appears to have an additional antiviral mechanism
      distal to viral integration. Our laboratories are attempting to determine the
      mechanism by which oltipraz inhibits HIV-1 replication in chronically infected
      cells; we are also attempting to determine the bioorganic mechanism for the
      inactivation of RT. Since the covalent modification of schistosomal proteins and
      transcription factor(s) are thought to be responsible for the antiparasitic and
      chemopreventive activities of DTTs, respectively, our studies should be relevant
      to understanding the diverse medicinal properties of DTTs. Oltipraz, an
      antischistosomal drug undergoing clinical evaluation as an anticarcinogen,
      inhibits HIV-1 replication at concentrations achievable in human serum. It is
      intriguing to consider oltipraz as a therapeutic agent not only for its
      antiretroviral activity, but also for the prevention of HIV-1 associated
      neoplasms.

PMID- 8538189
TI  - Development of difluoromethylornithine as a chemoprevention agent for the
      management of colon cancer.
AB  - Experimental studies have demonstrated that carcinogenesis is a multistep process
      in which inappropriate proliferation of cells is a critical determinant.
      Polyamines support sustained growth and are highly regulated in all cells. The
      rate limiting enzyme for this pathway is ornithine decarboxylase (ODC), an enzyme
      that exhibits rapid turnover, and converts the amino acid ornithine to
      putrescine, which in turn is converted to the longer chain amines spermidine and
      spermine. In animal models of colon carcinogenesis, inhibition of ODC by
      difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor,
      reduces the number and size of colon adenomas and carcinomas. DFMO was first
      ineffective when used clinically to treat acute leukemia or melanoma and caused
      clinically significant but reversible ototoxicity. Subsequently, we performed a
      series of analyses demonstrating that hearing loss was rare below a total
      cumulative dose of 150 gm/m2 and increased with total cumulative dose of DFMO.
      The hearing loss was reversible with rapid reversion to baseline hearing. We and
      others have conducted Phase IIa trials to determine the lowest dose at which DFMO
      can decrease colon mucosa polyamine content, and found that an oral dose as low
      as 0.25 gm/m2 per day (perhaps lower) decreases colon tissue putrescine content
      and lowers the spermidine/spermine ratio. We are currently conducting a long-term
      randomized Phase IIb trial which serially measures the long-term effect of
      several low doses (and placebo) of DFMO on sustaining polyamine depletion in
      colon mucosa, as well as carefully monitoring hearing by audiometry and other
      sophisticated tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538190
TI  - Ornithine decarboxylase as a target for chemoprevention.
AB  - l-Ornithine decarboxylase (ODC) is essential for polyamine synthesis and growth
      in mammalian cells; it provides putrescine that is usually converted into the
      higher polyamines, spermidine and spermine. Many highly specific and potent
      inhibitors of ODC are based on the lead compound alpha-difluoromethylornithine
      (DFMO), which is an enzyme-activated irreversible inhibitor. DFMO is accepted as
      a substrate by ODC and is decarboxylated, leading to the formation of a highly
      reactive species that forms a covalent adduct with either cysteine-360 (90%) or
      lysine-69 (10%). Both modifications inactivate the enzyme. ODC activity is
      normally very highly regulated at both transcriptional and post-transcriptional
      levels according to the growth state of the cell and the intracellular polyamine
      content. Experimental over-production of ODC can be caused by either transfection
      with plasmids containing the ODC cDNA with part of the 5'-untranslated region
      (5'UTR) deleted under the control of a very strong viral promoter, or
      transfection of plasmids that cause the overproduction of eIF-4E, reported to be
      a limiting factor in the translation of mRNAs with extensive secondary structures
      in the 5'UTR. In both cases, unregulated overexpression of ODC transforms NIH 3T3
      cells to a neoplastic state. Along with studies showing that many tumor promoters
      increase ODC activity and that a number of preneoplastic conditions and tumor
      samples show high levels of ODC, these results suggest that ODC may act as an
      oncogene in an appropriate background. This provides a rationale for the possible
      use of ODC inhibitors as chemopreventive agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538191
TI  - Prevention and therapy of mammary cancer by monoterpenes.
AB  - Monoterpenes, found in a wide variety of plants, are a major component of plant
      essential oils. The unsubstituted monocyclic monoterpene limonene has been shown
      to prevent carcinogen-induced mammary cancer at both the initiation and the
      promotion/progression stages. This terpene also causes the complete regression of
      the majority of advanced rat mammary cancer when added to the diet. Modification
      of limonene by hydroxylation at various positions increases both its
      chemopreventive and therapeutic efficacy. For example, the naturally occurring
      hydroxylated limonene analog perillyl alcohol is 5-10 times more potent than
      limonene and has a similar therapeutic index. Several cellular, metabolic and
      molecular activities are associated with terpene exposure. These include
      induction of phase I and II hepatic detoxification enzymes, selective inhibition
      of protein isoprenylation, inhibition of CoQ synthesis, and induction of the
      mannose 6-phosphate/IGFII receptor and TGF beta. Due to the therapeutic efficacy
      of monoterpenes in experimental model systems, clinical evaluation of this class
      of compounds has begun in advanced cancer patients. A Phase I trial of limonene
      is in progress in the UK. Efforts in the US will target perillyl alcohol for
      Phase I testing. Pre-IND toxicology is currently being completed. Phase I trails
      are anticipated to begin in the Spring of 1995. We feel that the results of these
      therapeutic trials, if positive, will facilitate the development of current
      terpenes and more potent analogs for future chemoprevention trials.

PMID- 8538192
TI  - Development of inhibitors of protein farnesylation as potential chemotherapeutic
      agents.
AB  - Protein prenylation, adding either the 15-carbon isoprenoid farnesyl or the 20
      carbon isoprenoid geranylgeranyl to cysteine residue(s) at or near the C-termini
      of proteins, is a recently identified post-translational modification that
      localizes some proteins to a membrane compartment. One of the most intensely
      studied prenylated proteins is Ras, a low molecular weight GTP-binding protein
      that plays an important role in the regulation of cell proliferation. Proteins
      encoded by ras genes with oncogenic mutations are capable of transforming cells
      in culture. Such mutated ras genes are frequently found in a wide variety of
      human tumors. Localization of the Ras oncoprotein to the cytoplasmic face of the
      plasma membrane via farnesylation is essential for efficient cell transforming
      ability. Thus, inhibition of the Ras farnesylation reaction is a possible anti
      cancer strategy. Several strategies have been employed to inhibit Ras
      farnesylation, including inhibition of isoprenoid biosynthesis and inhibition of
      the enzyme which catalyzes the farnesylation reaction, farnesyl-protein
      transferase (FPTase). Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, the rate limiting enzyme in isoprenoid biosynthesis, inhibit Ras
      farnesylation and block the growth of ras-transformed cells. However,
      antiproliferative effects do not result from specific inhibition of Ras
      farnesylation; they are also observed in cells transformed by raf, which is
      independent of Ras farnesylation. A more specific approach to inhibiting Ras
      farnesylation is to inhibit FPTase. Using random screening of natural products
      and a rational design approach, a variety of compounds that specifically inhibit
      FPTase have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538193
TI  - Probing the molecular program of apoptosis by cancer chemopreventive agents.
AB  - This paper provides a rational molecular basis for studies intended to clarify
      the interactions between cancer chemopreventive agents and apoptosis, one of the
      natural forms of cell death that overlaps molecular mechanisms with other forms
      such as programmed cell death and specialized forms of physiological cell death.
      Molecular details of the process show the existence of distinct molecular
      pathways leading to the activation of critical effector elements (apoptosis gene
      products) functioning under the control of a network of negative regulatory
      elements. Dysregulation of either apoptosis or anti-apoptosis genes has a
      significant role in multistage carcinogenesis. Inhibition of apoptosis is one of
      the underlying mechanisms of the action of tumor promoters. The network of
      apoptosis and anti-apoptosis gene products provides multiple targets for
      compounds with cancer chemopreventive potential. Many data in the literature show
      initiating, potentiating or inhibitory effects of such compounds on apoptosis.
      However, the molecular mechanism of these effects is largely unknown. We
      initiated a series of studies using mouse thymocytes which undergo apoptosis
      through distinct molecular mechanisms after T-cell receptor activation (TCR
      pathway), following the addition of glucocorticoids (DEX pathway) or DNA damaging
      agents (p53 pathway). All trans-and 9-cis-retinoic acid induced apoptosis,
      elicited through the DEX pathway, inhibited the TCR pathway, and did not affect
      p53- initiated apoptosis. N-acetylcysteine can inhibit all forms. Sodium
      salicylate enhanced spontaneous cell death, decreased p53-dependent apoptosis,
      and did not affect the DEX and TCR pathways. These preliminary results, which
      show differential effects of the studied compounds on distinct molecular pathways
      of apoptosis, warrant further investigations in the effort to utilize the
      molecular elements of apoptosis in proper cancer chemoprevention, and find
      biochemical targets for apoptosis-related surrogate endpoint biomarker assays of
      chemoprevention.

PMID- 8538194
TI  - Chalcones, myo-inositol and other novel inhibitors of pulmonary carcinogenesis.
AB  - The objective of the studies reported here has been to find novel chemopreventive
      agents effective against carcinogenesis of the lung. In particular,
      identification of suppressing agents, i.e., compounds preventing the evolution of
      the neoplastic process, has been sought. For this purpose, inhibition of
      pulmonary neoplasia in female A/J mice given the test agent starting one week
      after the last administration of three doses of benzo[a]pyrene has been employed
      as the experimental model. Under these conditions, chalcone, 4'
      methoxychalcone,myo-inositol, dexamethasone, and "terpeneless" orange oil added
      to the diet suppressed pulmonary adenoma formation. Chalcone and 4'
      methoxychalcone are open chain flavonoids, neither of these compounds occurs
      naturally, and their mechanism of action is not known. myo-Inositol is a
      naturally occurring compound of particular interest because of its exceedingly
      low toxicity. Dexamethasone is a potent glucocorticoid. Amongst its biological
      properties is the capacity to induce maturation of Type 2 alveolar cells and to
      stimulate production of surfactant by these cells. "Terpeneless" orange oil is a
      fraction of orange oil consisting predominantly of compounds with carbonyl or
      hydroxyl groups. The constituent or constituents responsible for the inhibitory
      effects observed is not known. The above studies are in an early phase of
      development and their ramifications remain to be determined.

PMID- 8538195
TI  - Polyphenols as cancer chemopreventive agents.
AB  - This article summarizes available data on the chemopreventive efficacies of tea
      polyphenols, curcumin and ellagic acid in various model systems. Emphasis is
      placed upon the anticarcinogenic activity of these polyphenols and their proposed
      mechanism(s) of action. Tea is grown in about 30 countries and, next to water, is
      the most widely consumed beverage in the world. Tea is manufactured as either
      green, black, or oolong; black tea represents approximately 80% of tea products.
      Epidemiological studies, though inconclusive, suggest a protective effect of tea
      consumption on human cancer. Experimental studies of the antimutagenic and
      anticarcinogenic effects of tea have been conducted principally with green tea
      polyphenols (GTPs). GTPs exhibit antimutagenic activity in vitro, and they
      inhibit carcinogen-induced skin, lung, forestomach, esophagus, duodenum and colon
      tumors in rodents. In addition, GTPs inhibit TPA-induced skin tumor promotion in
      mice. Although several GTPs possess anticarcinogenic activity, the most active is
      (-)-epigallocatechin-3-gallate (EGCG), the major constituent in the GTP fraction.
      Several mechanisms appear to be responsible for the tumor-inhibitory properties
      of GTPs, including enhancement of antioxidant (glutathione peroxidase, catalase
      and quinone reductase) and phase II (glutathione-S-transferase) enzyme
      activities; inhibition of chemically induced lipid peroxidation; inhibition of
      irradiation- and TPA-induced epidermal ornithine decarboxylase (ODC) and
      cyclooxygenase activities; inhibition of protein kinase C and cellular
      proliferation; antiinflammatory activity; and enhancement of gap junction
      intercellular communication. Curcumin is the yellow coloring agent in the spice
      tumeric. It exhibits antimutagenic activity in the Ames Salmonella test and has
      anticarcinogenic activity, inhibiting chemically induced preneoplastic lesions in
      the breast and colon and neoplastic lesions in the skin, forestomach, duodenum
      and colon of rodents. In addition, curcumin inhibits TPA-induced skin tumor
      promotion in mice. The mechanisms for the anticarcinogenic effects of curcumin
      are similar to those of the GTPs. Curcumin enhances glutathione content and
      glutathione-S-transferase activity in liver; and it inhibits lipid peroxidation
      and arachidonic acid metabolism in mouse skin, protein kinase C activity in TPA
      treated NIH 3T3 cells, chemically induced ODC and tyrosine protein kinase
      activities in rat colon, and 8-hydroxyguanosine formation in mouse fibroblasts.
      Ellagic acid is a polyphenol found abundantly in various fruits, nuts and
      vegetables. Ellagic acid is active in antimutagenesis assays, and has been shown
      to inhibit chemically induced cancer in the lung, liver, skin and esophagus of
      rodents, and TPA-induced tumor promotion in mouse skin.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8538196
TI  - Do NSAIDs exert their colon cancer chemoprevention activities through the
      inhibition of mucosal prostaglandin synthetase?
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) have considerable potential as
      chemopreventive agents for colorectal cancer. Recent case-control drug
      surveillance and large cohort studies found that patients with regular aspirin
      use had a reduced incidence of colorectal cancer and/or decreased death rate from
      this disease. Several different NSAIDs reduce formation of both colon adenomatous
      polyps (the precursor lesion of colon cancer) and cancers in experimental animals
      given known carcinogens. Perhaps most convincing are reports that the NSAID
      sulindac promotes regression and inhibits recurrence of adenomatous colon polyps
      in patients with adenomatous polyposis coli. The best characterized pharmacologic
      effect of the NSAIDs is their reduction of prostaglandin synthesis by inhibiting
      prostaglandin synthetase PGE2, which catalyzes the formation of prostaglandin
      precursors from arachidonic acid. Several lines of evidence are contrary to the
      concept that inhibition of prostaglandin synthesis is central to the NSAIDs'
      chemopreventive effects. Relatively high levels of prostaglandins have been
      reported to inhibit tumor cell growth both in vivo and in vitro, and to inhibit
      differentiation in some tumor cell lines. We evaluated comparative
      chemopreventive effects on colon tumor formation in an azoxymethane (AOM)-induced
      colon carcinogenesis rat model using the NSAIDs piroxicam, sulindac, and sulindac
      sulfone, a metabolite of sulindac which lacks the anti-prostaglandin synthetase
      activity typically associated with NSAID-induced gastrointestinal toxicities. The
      results demonstrate that sulindac sulfone, a compound lacking anti-prostaglandin
      synthetase activity, inhibits AOM-induced colon cancer in rats. Substantial dose
      dependent reductions in both tumor burden and tumor multiplicity were observed in
      the sulindac sulfone-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538197
TI  - Rationale for the use of genistein-containing soy matrices in chemoprevention
      trials for breast and prostate cancer.
AB  - Pharmacologists have realized that tyrosine kinase inhibitors (TKI) have
      potential as anti-cancer agents, both in prevention and therapy protocols.
      Nonetheless, concern about the risk of toxicity caused by synthetic TKIs
      restricted their development as chemoprevention agents. However, a naturally
      occurring TKI (the isoflavone genistein) in soy was discovered in 1987. The
      concentration of genistein in most soy food materials ranges from 1-2 mg/g.
      Oriental populations, who have low rates of breast and prostate cancer, consume
      20-80 mg of genistein/day, almost entirely derived from soy, whereas the dietary
      intake of genistein in the US is only 1-3 mg/day. Chronic use of genistein as a
      chemopreventive agent has an advantage over synthetic TKIs because it is
      naturally found in soy foods. It could be delivered either in a purified state as
      a pill (to high-risk, motivated patient groups), or in the form of soy foods or
      soy-containing foods. Delivery of genistein in soy foods is more economically
      viable ($1.50 for a daily dose of 50 mg) than purified material ($5/day) and
      would require no prior approval by the FDA. Accordingly, investigators at several
      different sites have begun or are planning chemoprevention trials using a soy
      beverage product based on SUPRO, an isolated soy protein manufactured by Protein
      Technologies International of St. Louis, MO. These investigators are examining
      the effect of the soy beverage on surrogate intermediate endpoint biomarkers
      (SIEBs) in patients at risk for breast and colon cancer, defining potential SIEBs
      in patients at risk for prostate cancer, and determining whether the soy beverage
      reduces the incidence of cancer recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538198
TI  - Effects of protease inhibitors on levels of proteolytic activity in normal and
      premalignant cells and tissues.
AB  - Our studies utilizing different types of protease inhibitors as anticarcinogenic
      agents in in vivo and in vitro systems have recently been reviewed. These studies
      suggest that the protease inhibitors which prevent carcinogenesis affect
      processes in the early stages of carcinogenesis, although they can be effective
      at long time periods after carcinogen exposure in both in vitro and in vivo
      systems. While there is strong evidence that these protease inhibitors can affect
      both the initiation and promotion stages of carcinogenesis, they have no effect
      on already transformed cells. Our results have suggested that the first event in
      carcinogenesis is a high frequency epigenetic event and that a later event,
      presumably genetic, leads to the malignant state. Protease inhibitors appear
      capable of reversing the initiating event, presumably by stopping an ongoing
      cellular process begun by carcinogen exposure. The major lines of investigation
      on the mechanism of the protease inhibitor suppression of carcinogenesis relate
      to the ability of anticarcinogenic protease inhibitors to affect the expression
      of certain oncogenes, and the levels of certain types of proteolytic activities.
      The anticarcinogenic protease inhibitors have no observable effects on normal
      cells, but can reverse carcinogen-induced cellular changes for several different
      end-points studied. The most direct method of determining the mechanism of action
      of the anticarcinogenic protease inhibitors is to identify and characterize the
      proteases with which they interact. In the cells of the in vivo and in vitro
      systems in which protease inhibitors can prevent carcinogenesis, only a few
      proteases have been observed to interact with the anticarcinogenic protease
      inhibitors. Proteases have been identified by both substrate hydrolysis and
      affinity chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538199
TI  - Chemoprevention by isothiocyanates.
AB  - Naturally occurring and synthetic isothiocyanates are among the most effective
      chemopreventive agents known. A wide variety of isothiocyanates prevents cancer
      in the rat lung, mammary gland, esophagus, liver, small intestine, colon, and
      bladder. Mechanistic studies have shown that this chemopreventive activity is due
      to favorable modification of phase I and phase II carcinogen metabolism,
      resulting in increased carcinogen excretion or detoxification and decreased
      carcinogen DNA interactions. Most studies reported that the isothiocyanate must
      be present at carcinogen exposure in order to effect tumorigenesis inhibition.
      Our studies focus on naturally occurring isothiocyanates phenethyl isothiocyanate
      (PEITC) and benzyl isothiocyanate (BITC) as lung cancer inhibitors. These studies
      employed the major lung carcinogens in tobacco smoke, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP). Combining chemopreventive
      agents that inhibit tumorigenesis by NNK and BaP in rodents may be effective in
      addicted smokers. PEITC inhibits lung tumor induction by NNK in F-344 rats and
      A/J mice, while BITC inhibits BaP-induced lung tumorigenesis in A/J mice;
      combining the two inhibits lung tumorigenesis by combined NNK and BaP in A/J
      mice. PEITC selectively inhibits metabolic activation of NNK in the rodent lung,
      while inducing glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL), one of the major NNK metabolites. Thus, PEITC decreases DNA and
      hemoglobin adduct formation by NNK while increasing the amounts of NNAL and its
      glucuronide excreted in the urine. Presently available data indicate that non
      toxic doses of PEITC can inhibit the metabolic activation and carcinogenicity of
      NNK in rat and mouse lung; BITC has similar effects on BaP activation and
      tumorigenicity in mouse lung. Thus, combinations of chemopreventive agents active
      against different carcinogens in tobacco smoke may be useful in the
      chemoprevention of lung cancer.

PMID- 8538200
TI  - Cancer prevention with dehydroepiandrosterone and non-androgenic structural
      analogs.
AB  - There is increasing evidence that the adrenocortical steroid,
      dehydroepiandrosterone (DHEA), is an important mammalian hormone. Administration
      of DHEA to laboratory mice and rats inhibits development of experimental tumors
      of the breast, lung, colon, liver, skin and lymphatic tissue. In the two-stage
      skin tumorigenesis model in mice, DHEA treatment inhibits tumor initiation, as
      well as tumor promoter-induced epidermal hyperplasia and promotion of papillomas.
      There is much evidence that DHEA produces its antiproliferative and tumor
      preventive effects by inhibiting glucose-6-phosphate dehydrogenase and the
      pentose phosphate pathway. This pathway is an important source of NADPH, a
      critical reductant for many biochemical reactions that generate oxygen free
      radicals, which may act as second messengers in stimulating hyperplasia. The
      therapeutic use of DHEA in humans may be limited by its sex hormonal side
      effects. DHEA is metabolized in vivo to both testosterone and estrone, producing
      both androgenic and estrogenic effects in laboratory animals. We have developed a
      synthetic steroid, 16 alpha-fluoro-5-androsten-17-one, which does not demonstrate
      the androgenic or estrogenic activity of DHEA, yet retains the antiproliferative
      and cancer preventive activity of the native steroid.

PMID- 8538201
TI  - The vitamin D Endocrine system: manipulation of structure-function relationships
      to provide opportunities for development of new cancer chemopreventive and
      immunosuppressive agents.
AB  - Biological responses mediated by vitamin D occur as a consequence of the
      integrated actions of the vitamin D endocrine system. The vitamin D endocrine
      system is characterized by the sequential two-step metabolism of vitamin D to 1
      alpha,25(OH)2D3 by the liver and kidney, and by the ability to generate
      biological responses in over 30 target tissues through nuclear receptor (nVDR)
      regulation of gene transcription and nongenomic pathways. It is now clear that
      the vitamin D endocrine system embraces many more target tissues than simply the
      intestine, bone and kidney. Notable additions to this list of tissues containing
      the nVDR include pancreatic B cells, pituitary gland, breast tissue, placenta,
      lymphocytes, keratinocytes, colon, and prostate, as well as many cancer cell
      lines. In addition to the classical actions of 1 alpha,25(OH)2D3 on mediating
      calcium homeostasis, this seco steroid has been identified as a potent stimulator
      of cell differentiation as well as an inhibitor of proliferation. Over the past
      decade at least 400 analogs of 1 alpha,25(OH)2D3 have been chemically synthesized
      and their biological properties systematically explored in a variety of assays
      which quantified both their calcemic effects and cell differentiating potential.
      The objective has been to identify new analogs devoid of the classical calcemic
      consequences of high doses of 1 alpha,25(OH)2D3, namely hypercalcemia, soft
      tissue calcification and nephrocalcinosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538202
TI  - beta-carotene and cancer chemoprevention.
AB  - Evidence supports the potential role of beta-carotene in cancer prevention. Basic
      research has demonstrated that beta-carotene can trap organic free radicals
      and/or deactivate excited oxygen molecules which may have an anticancer effect by
      preventing tissue damage. Although observational epidemiologic studies are not
      entirely consistent, many show an inverse association between dietary intake or
      blood levels of beta-carotene and subsequent cancer risk. Two large-scale
      randomized trials of beta-carotene have been completed. A Finnish trial
      demonstrated no benefit of beta-carotene among middle-aged male smokers, with
      those assigned to this supplement in fact experiencing an increased risk of lung
      cancer. However, because of the long latency period for cancer, which may be a
      decade or more, the six-year duration of treatment in this trial may have been
      inadequate to detect an anticancer effect. A Chinese trial demonstrated a modest
      reduction in cancer mortality from a combined regimen of beta-carotene, vitamin
      E, and selenium. The effect of the individual agents could not be assessed, and
      because the trial was carried out among a nutritionally deficient population, its
      results may not have direct relevance to well-nourished individuals. Several
      additional large-scale trials of beta-carotene are ongoing. The Physicians'
      Health Study, which is testing beta-carotene among 22,071 US male physicians,
      will have an average duration of treatment of 12.5 years at its scheduled
      termination in late 1995. Data in women will be available from the Women's Health
      Study, which began in 1992, and will randomize approximately 40,000 US female
      health professionals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538203
TI  - Cancer chemoprevention by natural carotenoids and their related compounds.
AB  - As one of the most promising cancer chemopreventive agents, beta-carotene has
      been studied extensively. However, other natural carotenoids have also suppressed
      tumorigenesis, and some are more potent than beta-carotene. For example, alpha
      carotene shows higher potency than beta-carotene in suppressing tumorigenesis in
      mouse skin and lung models. In the two-stage mouse skin carcinogenesis model
      (initiator, 7,12-dimethylbenz[a]anthracene; promoter, 12-O-tetradecanoylphorbol
      13-acetate), topical application of alpha-carotene at a 200 nmol dose per
      painting twice a week significantly decreased the mean number of skin tumors per
      mouse. The greater potency of alpha-carotene over beta-carotene in suppression of
      tumor promotion was confirmed in the two-stage mouse lung carcinogenesis model
      (initiator, 4-nitro-quinoline-1-oxide; promoter, glycerol). Oral administration
      of alpha-carotene (0.05% in drinking water) significantly decreased the mean
      number of lung tumors per mouse. In contrast, beta-carotene showed no suppression
      of lung tumor formation under the same experimental conditions. Fucoxanthin, a
      carotenoid as abundant in nature as beta-carotene, was also found to have
      antitumorigenic activity in mouse skin and duodenum models. Thus, further studies
      on various natural carotenoids, other than beta-carotene, should be carried out
      in the field of cancer chemoprevention.

PMID- 8538204
TI  - Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer.
AB  - Numerous epidemiological studies have demonstrated that consuming large
      quantities of fruits and vegetables reduces the risk for several types of human
      cancers. Carotenoids are abundant in fruits and vegetables and have been
      extensively studied as cancer preventive agents. A proposed mechanism of action
      for the protective effect of carotenoids against cancer is based on their
      antioxidant capability. Recently, we have isolated and characterized 14 new
      carotenoids, including seven metabolites from the extracts of human serum/plasma.
      This brings the total number of identified blood carotenoids to 21. Lutein and
      lycopene, abundant in most fruits and vegetables as well as human serum, have
      been shown to possess strong antioxidant capability. Among the metabolites of
      lutein, four results from oxidation and two from non-enzymatic dehydration. The
      metabolite of lycopene has been identified as 5,6-dihydroxy-5,6-dihydrolycopene,
      which apparently results from oxidation of lycopene to an intermediate, lycopene
      epoxide. This intermediate may undergo metabolic reduction to form the lycopene
      metabolite. Although in vivo oxidation of lutein to its metabolites has been
      demonstrated based on data obtained from two human studies, in vivo oxidation of
      lycopene to its metabolite has not yet been established. Recent preliminary
      studies involving healthy subjects ingesting purified lutein and zeaxanthin (a
      dietary dihydroxycarotenoid isomeric to lutein) are presented. We propose a
      possible antioxidant mechanism of action for lutein and lycopene that leads to
      formation of the oxidation products of these promising chemopreventive agents.

PMID- 8538205
TI  - N-acetylcysteine (NAC) and glutathione (GSH): antioxidant and chemopreventive
      properties, with special reference to lung cancer.
AB  - Lung cancer arises as a focal transformation of chronically injured epithelium
      with cigarette smoke as one of its well-recognized causes. Apart from oxidants
      (free radicals), cigarette smoke contains such a multitude of (pre)carcinogens
      that it is astonishing that not every heavy smoker becomes a victim of
      malignancy. This points to the interindividual variability in susceptibility to
      carcinogens; several lines of evidence suggest that metabolic factors are
      involved in such variability. Metabolism of carcinogens as well as the subsequent
      (multi)steps of carcinogenesis are affected by host factors and governed by the
      balance between opposing forces, such as metabolic activation and detoxification,
      formation and scavenging of radicals, and DNA damage and repair, which seem to
      imply that carcinogenic compounds can initiate tumor growth only in amounts
      saturating detoxification mechanisms. In this context it is well known that
      glutathione (GSH) plays a crucial role in the detoxification of xenobiotics. N
      Acetylcysteine (NAC), an aminothiol and synthetic precursor of intracellular
      cysteine and GSH, has been used for many years in Europe as a mucolytic drug.
      Clinically, it is a safe agent without major side effects and has been considered
      to have a place in cancer prevention, too. The antimutagenic and anticarcinogenic
      properties of NAC could be ascribed to multiple protective mechanisms, such as
      NAC nucleophilicity, antioxidant activity, its ability to act as a precursor of
      intracellular reduced GSH, modulation of detoxification, and DNA repair
      processes. On these grounds, NAC has emerged as a most promising cancer
      chemopreventive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538206
TI  - Butyrate and phenylacetate as differentiating agents: practical problems and
      opportunities.
AB  - Differentiating agents, including butyrate, phenylacetate and several other
      agents, have long been known to alter abnormal or transformed cell lines in vitro
      to a more normal state including phenotype and function. The effect depends on
      prolonged exposure to a minimum concentration of the agent. In vivo studies of
      butyrate and analogues have been limited, largely due to rapid in vivo
      metabolism. A butyrate prodrug, the triglyceride tributyrin, shows great promise
      in achieving effective and prolonged serum levels when given orally to mice and
      rats, and has been recommended for human trial. In vitro, butyrate and its mono-
      and triglyceride have shown potent synergy with retinoic acid, suggesting a ten
      fold reduction in serum level requirements. Other butyrate prodrugs have been
      prepared and studied; several sugar esters of butyrate show promise.
      Phenylacetate, a normal mammalian metabolite, is also a potent differentiating
      agent, but its clinical use is limited by its objectionable odor per se and in
      treated subjects. Phenylbutyrate, a prodrug of phenylacetate, is more acceptable
      and may have greater promise. The availability of effective prodrugs of effective
      differentiating agents, such as tributyrin and phenylbutyrate, creates many
      opportunities for possible therapeutic and chemopreventive applications,
      especially if synergy in vivo can be demonstrated with retinoids (e.g., retinoic
      acid) or deltanoids (e.g., active vitamin D analogues), confirming in vitro
      studies. Particular disease targets would include certain leukemias, thalassemia,
      and sickle cell anemia.

PMID- 8538207
TI  - Fostering chemopreventive agent development: how to proceed?
AB  - Improved molecular-based detection of early epithelial cancer creates an
      opportunity for selective pharmacologic agents to arrest the development of
      emerging cancers. Developing a successful prevention approach to cancer control
      could eventually lead to a significant decline in cancer mortality rates;
      progress depends on the amount of resources committed to this area. Most major
      prevention trials are federally supported due to their size, duration, and cost.
      Much of the initial developmental cost for advanced cancer treatment agents was
      supported by the pharmaceutical industry. Developing a cancer treatment agent is
      perceived as more clearly defined and achievable than for prevention agents.
      Preliminary discussions with representatives of the pharmaceutical and biotech
      industry have identified a number of barriers to chemoprevention product
      development. Researchers agree that a number of promising agents are being passed
      over for expeditious development due to the uncertainty associated with
      chemoprevention drug development. The major factors affecting this circumstance
      are considered, including cost of clinical trials, absence of a positive model,
      and inability to project liability exposure. Similar problems were encountered in
      the area of childhood vaccine development. Insights from that process may have
      applicability to prevention drug development. Resolving these problems now can
      have a significant effect on the rate of progress in this promising new approach
      to cancer control.

PMID- 8538208
TI  - Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental
      background.
AB  - The thiol N-acetylcysteine (NAC), now under clinical trial for cancer
      chemoprevention both in Europe (project Euroscan) and in the US (National Cancer
      Institute), has been shown during the past decade to exert protective effects in
      a variety of experimental test systems. NAC inhibited spontaneous mutagenicity
      and that induced by a number of chemical compounds and complex mixtures.
      Moreover, NAC significantly decreased the incidence of neoplastic and
      preneoplastic lesions induced by several chemical carcinogens in rodents (mice,
      rats, hamsters), e.g., in lung, trachea, colon, liver, mammary gland, Zymbal
      gland, bladder and skin. Our studies provided evidence that multiple mechanisms
      contribute to NAC antimutagenicity and anticarcinogenicity. They include
      extracellular mechanisms, such as detoxification of reactive compounds due to the
      nucleophilic and antioxidant properties of NAC, inhibition of nitrosation
      products, and enhancement of thiol concentration in intestinal bacteria; trapping
      and enhanced detoxification of carcinogens in long-lived non-target cells, such
      as erythrocytes and bronchoalveolar lavage cells; mechanisms working in the
      cytoplasm of target cells, such as replenishment of GSH stores, modulation of
      metabolism of mutagens/carcinogens, blocking of electrophiles, and scavenging of
      reactive oxygen species; and nuclear effects, such as inhibition of DNA adduction
      by metabolites of carcinogens, inhibition of "spontaneous" mutations, attenuation
      of carcinogen-induced DNA damage, and protection of nuclear enzymes, such as
      poly(ADP-ribose) polymerase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538209
TI  - Tamoxifen's role in chemoprevention of breast cancer: an update.
AB  - Tamoxifen is an oral antiestrogen first used in metastatic breast cancer in the
      early 1970s. Large clinical trials were initiated in the late 1970s and early
      1980s to test the drug's role as adjuvant therapy in early stage breast cancer.
      Observations of marked decreases in the development of contralateral breast
      cancer among tamoxifen recipients suggested potential for the drug in
      chemoprevention of breast cancer, and a large clinical trial to test the efficacy
      of tamoxifen in prevention of invasive breast cancer among women at increased
      risk was implemented in the United States in 1992. This paper reviews the
      rational for the clinical studies of tamoxifen as a chemopreventive agent for
      breast cancer and summarizes new information that has contributed to our
      understanding of tamoxifen's actions at the molecular and clinical levels.
      Current knowledge about the drug's mechanism of estrogenic and antiestrogenic
      action and its beneficial effects on blood lipids and bone metabolism will be
      presented. Recent research findings about DNA adduct formation and hepatic
      lesions, tamoxifen-associated gynecologic conditions, and the occurrence of
      second primary cancers in other organ systems will also be discussed.

PMID- 8538210
TI  - Alternate antiestrogens and approaches to the prevention of breast cancer.
AB  - The biological rationale and extensive clinical experience with the breast cancer
      drug tamoxifen make it the agent of choice for testing as a breast cancer
      preventive. However, concerns (Jordan and Morrow, Eur J Cancer, in press) about
      development of endometrial cancer in patients and liver tumors in rats with
      tamoxifen has encouraged the investigation of other antiestrogens. At present no
      compounds are available to replace tamoxifen, but two triphenylethylenes,
      toremifene and droloxifene, have been tested in postmenopausal women to treat
      advanced breast cancer. The response rates are similar to those observed with
      tamoxifen (i.e., approximately 35% [CR+PR] in unselected patients), although
      dosage regimens of the new antiestrogens are higher than the 20 mg tamoxifen
      required daily. Doses of up to 200 mg toremifene daily are being tested and
      studies use up to 100 mg droloxifene daily. Side effects appear comparable, but
      neither droloxifene nor toremifene produce liver tumors in rats. Tamoxifen
      produces DNA adducts, whereas toremifene and droloxifene appear to be only weakly
      active. A new tamoxifen analogue, idoxifene, is entering clinical trial. The drug
      is designed to be metabolically stable so that there will be low carcinogenic
      potential. In contrast, a novel strategy may be considered to be of value to
      protect women from developing breast cancer. It is known from laboratory and
      clinical studies that antiestrogens protect bone and prevent rat mammary cancer.
      One compound, raloxifene, is being tested as an agent to treat osteoporosis. If
      the drug becomes generally available to prevent osteoporosis in postmenopausal
      women, a beneficial side effect may be a reduction in breast cancer
      risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538211
TI  - Hormonally induced differentiation: a novel approach to breast cancer prevention.
AB  - Breast cancer, one of the most common neoplasms in women, develops more
      frequently in those who are nulliparous or late parous, who experience early
      menarche and late menopause and have a family history of breast cancer. Early
      parity, late menarche, early menopause, and hormone deprivation exert a
      protective effect. The mechanisms modulating these variations in malignancy
      susceptibility are not known. Epidemiologic and experimental studies indicate
      that malignancies develop in the mammary gland as a result of exposure to
      carcinogenic stimuli (i.e., chemical carcinogens, radiation). Neoplastic
      transformation requires that the gland be under specific developmental and age
      related conditions at the time of exposure to such agents. In the rat, maximal
      susceptibility to neoplastic transformation is exhibited by the highly
      proliferating and undifferentiated gland of the young, virgin, intact females,
      whereas the fully differentiated gland of parous rats and virgin rats treated
      with the placental hormone human chorionic gonadotropin is protected from tumor
      development. Hormonally induced differentiation of the mammary gland is a novel
      approach to breast cancer prevention and therapy. The development of clinical
      protocols capitalizing on the protective effect of hormonal treatments mimicking
      pregnancy in humans is required to validate observations in experimental animal
      models, and to determine how they relate to epidemiologic and clinical findings.
      The feasibility of this approach is supported by the observed parallelism between
      humans and experimental models in both the site of cancer origin and the changes
      in breast development occurring with parity. Breast cancer initiates in terminal
      ductal lobular units or lobules type 1, the most undifferentiated structures
      frequently found in the breast of young nulliparous women.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8538212
TI  - Calcium and the prevention of colon cancer.
AB  - Chemoprevention studies utilizing calcium have now progressed from basic
      measurements to clinical trials. Calcium's effects on epithelial cells have
      demonstrated decreased proliferation and induced cell differentiation with
      increasing levels of calcium in vitro, similar in vivo effects in rodent and
      human colon, and decreased carcinogen-induced colonic tumor formation in rodents.
      Current studies are attempting to inhibit colonic adenoma formation in human
      subjects. Most but not all epidemiologic studies also link increased dietary
      calcium with a decreased risk of colon cancer. In animal models, supplemental
      dietary calcium has decreased mammary epithelial cell hyperplasia and
      hyperproliferation and colonic cell hyperproliferation when the latter was
      induced by bile acids, fatty acids, and partial resection of the small intestine.
      Supplemental dietary calcium also decreased carcinogen-induced colonic tumors in
      several rodent models. In normal mice, and in mice carrying a targeted apc gene
      mutation, we recently increased colonic polypoid hyperplasias by a Western-style
      diet containing low calcium and vitamin D. In human subjects at increased risk
      for colon cancer, oral calcium supplementation significantly reduced colonic
      epithelial cell proliferation in most of the studies, including four randomized
      clinical trials. These studies have now progressed to short-term human clinical
      trials, including trials that measure the regrowth of transformed adenoma cells.
      Short-term adenoma-regrowth clinical trials, however, are limited in their
      ability to measure whether chemopreventive agents inhibit early genotoxic events,
      abnormal cellular metabolic activities involved in tumor promotion over many
      years, or the progression of adenoma cells to carcinoma.

PMID- 8538213
TI  - Calcium-cell cycle regulator, differentiator, killer, chemopreventor, and maybe,
      tumor promoter.
AB  - Ca2+ and Ca(2+)-binding proteins are involved in running the cell cycle. Ca2+
      spikes and signals from integrin-activated focal adhesion complexes and Ca2+
      receptors on the cell surface along with cyclic AMP begin the cycle of cyclin
      dependent protein kinases (PKs). These transiently expressed PKs stimulate the
      coordinate expression of DNA-replicating enzymes, activate replication enzymes,
      inactivate replication suppressors (e.g., retinoblastoma susceptibility protein),
      activate the replicator complexes at the end of the G1 build-up, and when
      replication is complete they and a Ca2+ spike trigger mitotic prophase. Another
      Ca2+ surge at the end of metaphase triggers the destruction of the prophase
      stimulating PKs and starts anaphase. Ca2+ finally stimulates cytoplasmic division
      (cytokinesis). However, Ca2+ does more than this in epithelial cells, such as
      those lining the colon, and skin keratinocytes. These cells also need Ca2+,
      integrin signals, and only a small amount (e.g., 0.05-0.1 mM) of external Ca2+ to
      start DNA replication. Signals from their surface Ca2+ receptors trigger a
      combination of differentiation and apoptosis ("diffpoptosis") when external Ca2+
      concentration reaches their setpoints. The skin's steep, upwardly directed, Ca2+
      gradient has a low concentration in the basal layer to allow stem and precursor
      keratinocytes to proliferate, and higher concentrations in the suprabasal layers
      to trigger the differentiation-apoptosis ("diffpoptosis") mechanism that converts
      granular cells into protective, hard-shelled, dead corneocytes. A similar Ca2+
      gradient may exist in the colon crypt allowing the stem cell and its amplifying
      transit or precursor offspring to cycle in the lower parts of the crypt, while
      stopping proliferation and stimulating terminal differentiation in the upper
      crypt and flat mucosa. Raising the amount of Ca2+ in fecal water above a critical
      level reduces proliferation and thus colorectal carcinogenesis in normal rats and
      some high-risk humans. But during carcinogenesis the Ca2+ sensors malfunction or
      their signals become ineffective: high Ca2+ does not stop, and may even
      stimulate, the proliferation of initiated mutants. Therefore, Ca2+ may either not
      affect, or even promote, the growth of epithelial cells in carcinogen-initiated
      rat colon and human adenoma patients. Clearly, a much greater understanding of
      how Ca2+ controls the proliferation and differentiation of epithelial cells and
      why initiated cells lose their responsiveness to Ca2+ are needed to assess the
      drawbacks and advantages of using Ca2+ as a chemopreventor.

PMID- 8538215
TI  - Effect of ionic strength and outer surface charge on the mechanical stability of
      the erythrocyte membrane: a linear hydrodynamic analysis.
AB  - A linear hydrodynamic analysis in normal modes has been developed for a membrane
      model that simulated the erythrocytes membrane. The characteristic dispersion
      equation was obtained by solving the linearized dynamic equations. Values of the
      parameters related to the erythrocyte membrane were used to obtain the critical
      stability curves as a function of cell surface electric charge and suspending
      phase ionic strength. According to this model, the mechanical stability of the
      membrane increases with the decrease of the negative charge value on the outer
      membrane surface. The conclusion is that the transmembrane-potential and surface
      charge changes that follow the reduction in ionic strength were responsible for
      the stability increase observed in previously reported experiments on heated
      erythrocytes.

PMID- 8538214
TI  - Chemoprevention of cancer by organoselenium compounds.
AB  - A major research goal of our laboratories is the development of new
      organoselenium cancer chemopreventive agents with less toxicity compared to some
      of the historical selenium compounds, such as sodium selenite. Ideally, such
      agents would be employed to inhibit tumor development in different organs caused
      by a variety of chemical carcinogens, particularly those present in the human
      environment. A series of organoselenium compounds has been synthesized and
      evaluated for their chemopreventive efficacy in vivo. Parallel to these studies,
      short-term in vitro and in vivo assays were employed to understand the mechanism
      of action and to rapidly evaluate their efficacy in eventual long-term
      preclinical investigations. We demonstrated that one of the most effective of
      these organoselenium compounds, 1,4-phenylenebis(methylene)selenocyanate (p-XSC,
      Fig. 1), is capable of inhibiting tumors in the mammary glands, colon, and lung
      of laboratory animals. Dietary p-XSC inhibited mammary tumor development induced
      by 7,12-dimethylbenz(a)anthracene (DMBA) during both the initiation and post
      initiation phases of carcinogenesis in female CD rats. p-XSC inhibited DMBA-DNA
      adduct formation in the mammary glands. In collaboration with other laboratories,
      we demonstrated that p-XSC inhibited thymidine kinase in mammary tumor cell lines
      derived from both humans and rats. Employing mammary carcinoma cell lines, p-XSC
      was also shown to inhibit cell growth and induce a dose-dependent increase in
      cell death by apoptosis. In these assays p-XSC appears superior to selenite and
      to its sulfur analog, 1,4-phenylenebis(methylene)thiocyanate. Dietary p-XSC
      decreased colon tumor induction by azoxymethane in F344 rats during both phases
      of carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538216
TI  - Comments on "Let there be life; thermodynamic reflections on biogenesis and
      evolution" by Avshalom C. Elitzur.
AB  - This comment is in response to a paper previously published in the Journal
      entitled "Let there be life", by A. C. Elitzur. Elitzur ascribes to Eigen the
      proposal that life began with the appearance of an autocatalytic (self
      replicating) molecule. This was discussed by biologists and philosophers in the
      nineteenth century. Eigen's proposal is moot: there never was a primeval soup.
      The absence of evidence is evidence of absence. Elitzur also confuses
      thermodynamics with statistical mechanics. The statistical equation of Boltzmann
      and Planck for entropy appears in discussions of statistical mechanics, not in
      discussions of classical thermodynamics. Elitzur calls the Second Law of
      Thermodynamics an explanation of evolution. On the contrary, his mentor Eigen
      wrote: "In physics we know of principles which cannot be reduced to any more
      fundamental laws. As axioms, they are abstracted from experience, their
      predictions being consistent with the consequences that can be subjected to
      experimental test. "Typical examples are the first and second law of
      thermodynamics. Darwin's principle of natural selection does not fall into the
      category of first principles." The reader is invited to compare the material in
      Elitzur's paper with the discussion in Yockey's (1992) book, Information Theory
      and Molecular Biology, Cambridge, Cambridge University Press.

PMID- 8538217
TI  - Forms of early walking.
AB  - Children in the first weeks of independent locomotion display a wide variety of
      walking forms. The walking forms differ in mechanical strategy and concern with
      balance. Three extreme walking forms are presented: the Twister, who uses trunk
      twist, the Faller, who uses gravity, and the Stepper, who remains balanced as
      much as possible. Each walking form is presented as a "d-space", a mathematical
      format combining continuous and discrete aspects, developed to express the
      sequence and pattern of a movement without the inappropriate precision of a
      physical trajectory. The three d-spaces represent analyses of three extreme modes
      of early walking. They are used to generate the variety of early walking forms
      and to predict mixtures of mechanical strategies as children mature and converge
      to more similar walking forms over the first few months of independent
      locomotion.

PMID- 8538218
TI  - The origin of synergistic symbiosis.
AB  - A dominant theme in the history of life has been the evolutionary innovations of
      cooperative symbioses: the first genomes near the origin of life, integrated
      prokaryotic cells, the complex symbiotic communities that evolved into modern
      eukaryotic cells, lichens, mycorrhizae, and so on. In this paper, a model of
      cooperative symbiosis that shows a threshold condition for the evolution of
      cooperation is analyzed. The threshold is not easily passed, but cooperative
      evolution proceeds rapidly once a symbiosis overcomes the threshold. In the model
      presented here, each species has genetic variability for a symbiotic trait. The
      trait imposes a reproductive cost on its bearer but enhances the reproduction of
      its partner species. For example, in the origin of genetic systems, the trait may
      cause biochemical synergism for the rate of replication of primitive RNA strands
      as in Eigen and Schuster's hypercycle model. Models of growth are contrasted with
      synergism, which are most appropriate for the evolution of genetic systems and
      for mutualisms such as lichens, with the strategic and psychological applications
      of the Prisoner's Dilemma model.

PMID- 8538219
TI  - A Monte Carlo simulation of the Escherichia coli cell cycle.
AB  - A Monte-Carlo simulation of the division cycle of an individual bacterium has
      been developed to test theories concerning the control of cell cycle events and
      for the analysis of cell cycle data. The model is based on the work of Cooper and
      Helmstetter and other theories concerning the control of DNA replication
      initiation, chromosome segregation and cell division. Variability in the
      molecular events that initiate a particular cell cycle event is incorporated
      using a Monte Carlo approach. The model results are compared with experimental
      data from a number of different sources and collected using a number of different
      analytical techniques. This model is able to accurately represent the cell size
      distributions of an exponentially growing population as determined by a Coulter
      Counter and the DNA distributions as determined by flow cytometry. The model is
      also able to accurately simulate the cell age distribution and chromosome
      replication and segregation patterns as determined by the membrane-elution
      technique. Results from parameter sensitivity analysis indicate that variability
      in the symmetry of cell division and in the cell size at initiation of chromosome
      replication have the most significant impact on the cell size, age and DNA
      distributions. Results from the membrane-elution simulation support the
      hypothesis that total cell protein is synthesized exponentially during the
      division cycle and that cell size control is a plausible explanation for control
      of DNA replication. The simulation results for chromosome segregation agree with
      experimental data and support chromosome strand segregation models. In the
      future, this simulation should be useful in testing complex theories about
      molecular control of cell cycle events against experimental data.

PMID- 8538220
TI  - Muscle contraction: are the crossbridges independent force generators?

PMID- 8538221
TI  - Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome: who
      should receive prophylaxis?

PMID- 8538222
TI  - Methotrexate for refractory Crohn's disease: preliminary answers to definitive
      questions.

PMID- 8538223
TI  - New visage for the "old reliable".

PMID- 8538224
TI  - Hepatitis C virus infection and cutaneous vasculitis in mixed cryoglobulinemia.

PMID- 8538225
TI  - Pulmonary hamartomas.
AB  - OBJECTIVE: To analyze the clinical and pathologic features of biopsy-proven
      pulmonary hamartomas at a tertiary referral center. DESIGN: We retrospectively
      reviewed institutional data on pulmonary hamartomas for a 17-year study period.
      MATERIAL AND METHODS: The Mayo Clinic computerized medical records database was
      searched for patients who had biopsy, excision, or autopsy diagnosis of pulmonary
      hamartomas from 1976 through 1992. Medical records and all available histologic
      sections were reviewed. RESULTS: Of the 215 patients with histologically
      confirmed pulmonary hamartoma, 141 were men and 74 were women (approximately a
      2:1 ratio). Two hundred eight patients were asymptomatic, 54 of whom were
      undergoing assessment for a comorbid disease process. Only four patients had new
      onset of respiratory symptoms. The peak incidence of occurrence was in the
      seventh decade of life. The mean size of the hamartomas were 1.5 cm (range, 0.2
      to 6.0); no lobe was predominantly involved. Most hamartomas were resected by
      simple or wedge excision. Sixty-three patients (29.3%) had a concurrent neoplasm
      (most commonly, lung carcinoma). Follow-up ranged from 2 to 192 months (mean,
      61). Eight postoperative deaths occurred. No recurrent pulmonary hamartomas
      developed. In one patient, lung carcinoma developed 33 months after excision of a
      hamartoma. In a second patient, sputum cytologic findings were abnormal 9 years
      later. A third patient had biopsy-proven adenocarcinoma metastatic to bone and an
      indeterminate lung nodule 2 years after resection of a pulmonary hamartoma.
      CONCLUSIONS: Pulmonary hamartomas are benign lung neoplasms that, in our referral
      population occurred most commonly in asymptomatic older men. A substantial number
      of our patients had concurrent neoplasms; however, many had been referred for
      cancer treatment. We found no evidence of either a malignant transformation or an
      unexplained association with other lung neoplasms.

PMID- 8538226
TI  - The importance of urinary magnesium values in patients with gut failure.
AB  - OBJECTIVE: To determine whether urinary magnesium (Mg) values in patients with
      gut failure would be more helpful than serum Mg measurements in assessment of Mg
      deficiency. DESIGN: We compared serum and urinary Mg values in 16 patients with
      gut failure and 16 age- and sex-matched control subjects. MATERIAL AND METHODS:
      Sixteen patients with gut failure (nine women and seven men; mean age, 59 years)
      had serum and 24-hour urinary mg measured before Mg replacement therapy. Short
      bowel syndrome was present in 75%, and diffuse small bowel disease was present in
      25%. RESULTS: The median value for serum Mg was 1.7 mg/dL for patients and 2.0
      mg/dL for healthy control subjects (P < 0.001). The median values for urinary Mg
      were 19 mg and 127 mg per 24-hour specimen in patient and control groups,
      respectively (P < 0.001). A strong correlation was noted between serum Mg and
      urinary Mg levels. All patients had low urinary Mg values even though 9 of 16
      (56%) had normal serum Mg values. Two patients with normal serum Mg
      concentrations had urinary Mg values of 20 mg/24 h (25% of normal). Serum, but
      not urinary, Mg correlated significantly with the length of remaining small bowel
      (P = 0.03). CONCLUSIONS: Urinary Mg declines before serum Mg and is an earlier
      and more reliable indicator of evolving Mg deficiency. On the basis of these
      observations and those showing beneficial effects of parenterally administered Mg
      supplements on urinary citrate excretion (and, presumably, formation of calcium
      oxalate stones), replacement of Mg in patients with gut failure should be
      targeted at normalizing urinary Mg.

PMID- 8538227
TI  - Chronic necrotizing pulmonary aspergillosis: pathologic outcome after
      itraconazole therapy.
AB  - OBJECTIVE: To characterize chronic necrotizing pulmonary aspergillosis (CNPA)
      clinically, radio-graphically, and pathologically and to describe its response to
      treatment. MATERIAL AND METHODS: We present three cases of well-documented CNPA
      and detail the long-term clinical and pathologic responses to the new antifungal
      triazole, itraconazole. RESULTS: Although all three patients had an appreciable
      clinical response to itraconazole therapy, tissue obtained at the time of
      operation or autopsy revealed residual CNPA despite 5 to 12 months of treatment.
      Even though pathologic resolution of the CNPA did not occur, patient prognosis
      was determined solely by comorbid illness. CONCLUSION: Itraconazole seems to be
      effective in CNPA when used in a suppressive (rather than curative) role in
      patients with limited life expectancy.

PMID- 8538228
TI  - Dumitru Bagdasar--father of Romanian neurosurgery.

PMID- 8538229
TI  - 1,25-dihydroxyvitamin D-mediated hypercalcemia in a renal transplant recipient.
AB  - Hypercalcemia occurs in 10 to 30% of renal transplant recipients and is most
      often due to persistent hyperparathyroidism. Herein we describe a patient with a
      history of hyperparathyroidism who sought medical assessment because of
      recurrence of hypercalcemia 7 years after a successful renal transplantation. The
      hypercalcemia was associated with a normal serum phosphate level, a low to normal
      parathyroid hormone level, virtually undetectable levels of parathyroid hormone
      related protein, and increased 1,25-dihydroxyvitamin D levels. Further assessment
      led to the diagnosis of an underlying lymphoma. To our knowledge, this is the
      first report of 1,25-dihydroxyvitamin D-mediated hypercalcemia in a renal
      transplant recipient with lymphoma. The possibility of an underlying
      lymphoproliferative disorder should be considered in the differential diagnosis
      of hypercalcemia in a renal transplant recipient.

PMID- 8538230
TI  - Percutaneous transcatheter embolization of coronary arteriovenous fistulas.
AB  - Coronary artery fistulas are infrequently encountered vascular communications
      that are either congenital or due to cardiac trauma. Most patients with these
      anomalies are asymptomatic, but late complications can occur and include
      congestive heart failure, myocardial ischemia, arrhythmias, and endocarditis.
      Therefore, many investigators have recommended surgical repair, even for
      asymptomatic patients. Although coronary arteriovenous fistulas pose many
      challenges to interventional cardiologists, early experiences suggest that these
      abnormal vessels can be successfully obliterated percutaneously; thus, the
      patient is spared the risks and morbidity associated with cardiac surgical
      intervention. Herein we present two cases that illustrate many of the technical
      issues involved in successful transcatheter embolization of coronary artery
      fistulas.

PMID- 8538231
TI  - Origin of the Mayo section of urology.

PMID- 8538232
TI  - Cardiovascular stress testing: a description of the various types of stress tests
      and indications for their use.
AB  - OBJECTIVE: To describe the various types of stress tests and to provide
      guidelines for selecting a specific test for an individual patient. MATERIAL AND
      METHODS: Myocardial perfusion imaging, radionuclide angiography, stress
      echocardiography, and cardiopulmonary exercise testing are described. The
      advantages and limitations of these techniques are reviewed and compared with
      those of standard treadmill exercise testing. The agents used for pharmacologic
      stress testing are discussed. RESULTS: Standard treadmill exercise testing is
      widely available and is less expensive than the imaging techniques. It is most
      accurate in patients with normal findings on a resting electrocardiogram who are
      not taking digoxin. In these patients, standard exercise electrocardiography is
      almost as accurate as the exercise imaging modalities for identifying those with
      left main or three-vessel coronary artery disease. Advantages of the stress
      imaging modalities in comparison with standard exercise electrocardiography
      include greater accuracy when the resting electrocardiogram shows abnormal
      findings, higher sensitivity, ability to localize and characterize the extent of
      myocardial ischemia, and direct measurement of other variables such as left
      ventricular function. These techniques must be performed carefully in experienced
      laboratories in order to provide accurate information. Published data are scant
      that directly compare one technique with another in the same set of patients. The
      nuclear cardiology techniques have been well validated for detecting left main
      and three-vessel coronary artery disease and for assessing prognosis. Myocardial
      perfusion imaging has been well validated for detecting ischemia in patients with
      abnormal left ventricular function at rest. In comparison with the nuclear
      cardiology techniques, stress echocardiography is less expensive and provides
      more ancillary information but has not been as well validated for assessment of
      severe coronary artery disease or prognosis. Cardiopulmonary exercise testing can
      be useful in selecting patients for cardiac transplantation and in assessing
      exertional dyspnea in selected patients. The most common application of
      pharmacologic stress testing is preoperative risk assessment of patients
      undergoing noncardiac operations. Pharmacologic stress testing should usually be
      reversed for patients who are unable to exercise adequately. CONCLUSION: Most
      patients with normal findings on a resting electrocardiogram who are not taking
      digoxin should undergo standard treadmill exercise testing for diagnostic and
      prognostic purposes. Most patients with abnormal findings on a resting
      electrocardiogram should undergo one of the stress imaging techniques. Selecting
      a specific stress imaging techniques. should depend primarily on local expertise
      with the various techniques and secondarily on the strengths and limitations of
      the techniques as they relate to the individual patient.

PMID- 8538233
TI  - Pneumocystis carinii pneumonia in patients without acquired immunodeficiency
      syndrome: associated illness and prior corticosteroid therapy.
AB  - OBJECTIVE: To determine the clinical spectrum of immunosuppressive conditions and
      systemic corticosteroid therapy associated with the development of Pneumocystis
      carinii pneumonia in a consecutive series of patients without acquired
      immunodeficiency syndrome (AIDS). DESIGN: We retrospectively analyzed a
      consecutive series of 116 patients without AIDS who were assessed at Mayo Medical
      Center for a first episode of P. carinii pneumonia between 1985 and 1991.
      METHODS: Medical records were examined to determine underlying immunosuppressive
      disorders, premorbid corticosteroid dosage and duration of therapy, associated
      infections, and subsequent respiratory failure and in-hospital mortality.
      RESULTS: Conditions associated with a first episode of P. carinii pneumonia were
      hematologic malignant disorders (30.2%), organ transplantation (25.0%),
      inflammatory disorders (22.4%), solid tumors (12.9%), and miscellaneous
      conditions (9.5%). Regardless of the associated underlying disease,
      corticosteroids had been administered systemically in 105 patients (90.5%) within
      1 month before the diagnosis of P. carinii pneumonia. The median daily
      corticosteroid dose was equivalent to 30 mg of prednisone; however, 25% of
      patients had received as little as 16 mg of prednisone daily. The median duration
      of corticosteroid therapy was 12 weeks before the development of pneumonia;
      however, P. carinii pneumonia developed after 8 weeks or less of corticosteroid
      therapy in 25% of these patients. Respiratory failure occurred in 43%, and in
      hospital mortality was 34% for patients with P. carinii pneumonia in conditions
      other than AIDS. CONCLUSION: Although these results do not suggest that premorbid
      administration of corticosteroids is the only factor that contributes to the
      development of P. carinii pneumonia in these patients, they show that, in this
      large consecutive series, systemic corticosteroid therapy, even in moderate
      doses, was administered to most patients during the month preceding the onset of
      P. carinii pneumonia. Consideration should be given to instituting P. carinii
      prophylaxis (when not contra-indicated) in patients for whom prolonged systemic
      corticosteroid therapy is prescribed.

PMID- 8538234
TI  - A practical guideline for management of hypertension in patients with diabetes.
AB  - Hypertension is common in patients with non-insulin-dependent diabetes mellitus
      and is also an early sign of diabetic nephropathy in those with insulin-dependent
      diabetes. Hypertension contributes to the progression of both macrovascular
      disease and nephropathy in patients with diabetes. Certain antihypertensive
      agents can adversely affect carbohydrate and lipid metabolism. Angiotensin
      converting enzyme inhibitors and calcium channel blockers may slow the
      progression of renal complications in patients with diabetes. The pharmacologic
      approaches to treatment of hypertension in patients with diabetes potentially
      differ from those in nondiabetic persons. On the basis of a review of the recent
      literature related to antihypertensive therapy for patients with diabetes, we
      describe an empiric approach to treatment of hypertension in such patients. The
      proposed approach must be modified as new data from randomized clinical trials
      become available.

PMID- 8538235
TI  - 35-year-old woman with ulcerating skin lesions.

PMID- 8538236
TI  - 47-year-old woman with chronic renal failure, chest pain, and a cardiac murmur.

PMID- 8538237
TI  - Cytogenetic testing for Williams syndrome.

PMID- 8538238
TI  - Methotrexate for inflammatory bowel disease: pharmacology and preliminary
      results.
AB  - OBJECTIVE: To review the limited published experience with methotrexate treatment
      for inflammatory bowel disease, to examine the proposed anti-inflammatory and
      immune-modifying mechanism of action and pharmacologic properties of
      methotrexate, and to detail its limiting toxicities. DESIGN: A comprehensive
      synopsis of methotrexate is presented to aid physicians who treat patients with
      inflammatory bowel disease. RESULTS: Methotrexate and its polyglutamate
      metabolites are folic acid analogues with inhibitory activity against many
      enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate
      therapy (25 mg or less once a week) inhibits production of thymidylate, purines,
      and methionine and leads to accumulation of adenosine, a potent anti-inflammatory
      substance. These actions inhibit cellular proliferation, decrease formation of
      antibodies, and decrease production of mediators of inflammation such as
      interleukins and eicosanoids. Three uncontrolled trials and two controlled trials
      have demonstrated efficacy of low-dose methotrexate therapy for induction of
      remission in Crohn's disease and have also suggested possible benefit for
      ulcerative colitis and for remission maintenance indications in both diseases.
      Although methotrexate is generally well tolerated for long-term use at a low
      dose, several serious toxicities potentially limit its use. CONCLUSION:
      Methotrexate is a promising new agent for the treatment of inflammatory bowel
      disease.

PMID- 8538239
TI  - Constipation and fecal incontinence in the elderly population.
AB  - OBJECTIVE: To describe the assessment and management of constipation and fecal
      incontinence in elderly patients. DESIGN: We reviewed pertinent publications in
      the recent medical literature and outlined effective management strategies for
      constipation and fecal incontinence in the geriatric population. RESULTS:
      Constipation can be classified into two syndromes--functional constipation and
      rectosigmoid outlet delay. Evaluation consists of elicitation of a detailed
      history, directed physical examination, and selected laboratory tests. Management
      involves nonpharmacologic (such as exercise and fiber) and pharmacologic
      measures. Fecal incontinence in elderly patients can be due to stool impaction,
      medications, dementia, or neuromuscular dysfunction. Management options include
      modification of contributing disorders, pharmacologic therapy, and behavioral
      techniques. CONCLUSION: Constipation and fecal incontinence are common and often
      debilitating conditions in elderly patients. Management should be highly
      individualized and dependent on cause, coexisting morbidities, and cognitive
      status.

PMID- 8538240
TI  - Urinary incontinence in the elderly population.
AB  - OBJECTIVE: To describe the causes, evaluation, and management of urinary
      incontinence in the elderly population. DESIGN: We reviewed pertinent articles in
      the medical literature and summarized the types of incontinence and contributing
      factors. RESULTS: Urinary incontinence is common in elderly patients and often
      has a major role in determining whether a person can remain independent in the
      community or requires nursing home placement. Urinary incontinence is not a
      single entity but rather several different conditions, each with specific
      symptoms, findings on examination, and recommended treatment. Thus, accurate
      classification is important for appropriate management. Because of the complexity
      of urinary incontinence, many physicians are uncomfortable with undertaking
      assessment and treatment. Hence, many patients are not asked about incontinence,
      and the condition remains untreated and often considered a natural consequence of
      the aging process. Urinary incontinence can be treated and either cured or
      alleviated with treatment. CONCLUSION: Elderly patients should be asked about
      symptoms of urinary incontinence because appropriate assessment and treatment can
      usually provide relief.

PMID- 8538241
TI  - Human lymphocytes incubated in vitro share multiple characteristics with
      geriatric-derived lymphocytes: a potential in vitro model for aging?
AB  - Aging involves a complicated set of parallel reactions that result in multiple
      cellular and organismic changes and may eventuate in chronic illness. In the
      immune system, several alterations that correlate with age have been established.
      In the present study, we report the results of incubating lymphocytes in vitro in
      whole blood and, employing measures known to be age-dependent, compare these
      cells 'aged' in vitro with cells from geriatric patients aged in vivo. Cells from
      blood aged in vivo and incubated in vitro share a number of common
      characteristics that include decreased growth capacity, shifted growth patterns,
      increased suppression by adherent cells, decrease in CD5 surface antigen, similar
      responses to addition of exogenous IL-1, IL-2, PGE2, or indomethacin, and similar
      production of PGE2. Differences found between in vivo aging and in vitro
      incubation are IL-2 plasma levels and IL-2 production by activated cells
      monitored in conditioned minimal medium. Based on these observations, this in
      vitro system provides a simple method to generate cells that exhibit a very
      significant subset, but not all, of the characteristics associated with in vivo
      aging in lymphocytes.

PMID- 8538242
TI  - Protective effect of vitamin E on lymphocyte growth capacity during incubation in
      vitro.
AB  - Vitamin E, an essential lipid-soluble micronutrient, plays an important role in
      the immune system and serves as an immunostimulant in geriatric subjects. Using
      an in vitro incubation to simulate aging processes, we find that vitamin E
      mitigates loss of growth capacity in lymphocytes. Vitamin E presence during in
      vitro incubation did not affect significantly the level of peroxidation, the
      effects of exogenous IL-2, PGE2, or indomethacin, nor levels of IL-2 production.
      Thus, the preservative effect on lymphocyte growth by vitamin E is not due
      primarily to its antioxidant function or to interleukin-2 or prostaglandin
      effects. The decreased growth capacity generated by in vitro incubation is
      accompanied by a variety of cellular alterations, including decreased CD5 surface
      antigen, enhanced suppression by adherent cells, and impaired communication
      between lymphocytes and adherent cells. The decrease in CD5 surface antigen
      correlates inversely with the cell density required for maximal cell
      proliferation, and the diminished CD5 levels were unaltered by vitamin E presence
      during the aging process. In contrast, protection of T-cell proliferative
      capacity by vitamin E in vitro correlates with diminished suppression by adherent
      cells and normalized interaction between lymphocytes and adherent cells.

PMID- 8538243
TI  - Age-related alterations in the morphology of femoral artery vasa vasorum in the
      rat.
AB  - The objective of this study was to explore any age-related morphological changes
      in the vasa vasorum of the rat femoral artery. Vascular corrosion casts were
      prepared from 2, 12 and 24-month-old rats. Examination of the casts with the
      scanning electron microscope revealed dramatic differences in the appearance of
      the vessels of young and aged rats. The vasa vasorum of 2-month-old rats
      consisted of a dense network of capillaries. These vessels were dramatically
      reduced in number by 12 months, and even fewer capillaries were present at 24
      months. This reduction in capillary density is consistent with the observed age
      related decreases in oxygen tension and may explain why the aged are more prone
      to atherosclerosis.

PMID- 8538244
TI  - The pattern of T lymphocyte differentiation is altered during thymic involution.
AB  - Thymic involution is likely to be a significant factor in the alteration of
      peripheral T lymphocyte function with age. The process of thymic involution
      involves the progressive loss of normal organ architecture and cellular
      composition, and a significant reduction in the output of mature T lymphocytes.
      The present study assesses the impact of thymic involution on the T cell
      differentiation process by quantitating the number and percent representation of
      various phenotypically distinguishable T cell developmental intermediates in
      C57BL/6 mice of various ages. The results suggest that several distinct sites in
      the developmental sequence are impacted by aging. By middle-age (14-17 months),
      significant perturbations in the frequencies of several CD4-CD8- (DN)
      subpopulations have occurred. These include a shift towards an increased
      percentage of Pgp-1+ IL-2R- DN cells, the earliest thymic progenitors, and a
      decreased percentage and total number of Pgp-1- IL-2R+ DN cells. Furthermore
      there is a threefold increase in the percentage of DN cells which express CD3
      (from 16.6% to 45.5%) which occurs between 4 and 14 months of age. By 24-27
      months of age, the percentage of the total DN population increases two- to
      threefold over that of young (2-3 months) animals, while the fraction of CD4+CD8+
      (DP) is significantly reduced. These alterations are consistent with the
      possibility that thymic involution results in one or more 'developmental' blocks
      which limit key differentiative transitions within the DN population, and
      furthermore, the marked increase in the frequency of DN cells displaying CD3
      argues that an alternative T cell differentiation pathway plays an increasingly
      significant role with advancing age.

PMID- 8538245
TI  - The influence of aging on dimethylnitrosamine-demethylase enzyme kinetics in rat
      liver microsomes.
AB  - To investigate the observed age-related increased susceptibility to chemically
      induced carcinogenesis, liver microsomes from 12- or 36-month-old rats either
      untreated or maximally induced with phenobarbital or isoniazid were used to
      determine the Vmax and Km for dimethylnitrosamine-demethylase (DMNA-d). A
      decrease in cytochrome P450 content between young and old animals was observed in
      the untreated group, but no change was seen in the treated animals. Inducer
      related increases were observed after phenobarbital treatment and in the 36-month
      old isoniazid-treated group. The Vmax for DMNA-d did not change between 12 and 36
      months of age in all experimental groups, but significant changes between the
      young and old age-group and inducer-related differences were observed in the
      Km,app for DMNA-d. A high correlation was found between the Cl(int) (=
      Vmax/Km,app) of DMNA-d and the Vmax of p-nitrophenol-hydroxylation, indicating a
      major role for CYP2E1 in the metabolism of DMNA-d. The observed changes in the
      cytochrome-P450 levels and the reduced affinity in DMNA-d metabolism in the
      untreated group in this study is another indication that aging predominately
      affects the activity of some constitutive cytochrome P450 enzymes but not the
      activity of the inducible types of P450.

PMID- 8538246
TI  - Age-related changes in basic fibroblast growth factor-immunoreactive cells of rat
      substantia nigra.
AB  - Immunohistochemistry and computer-assisted image analysis were used to examine
      the age-related changes in bFGF-immunoreactivity in rat substantia nigra (SN).
      Distribution pattern, number, size and staining intensity of bFGF-immunoreactive
      (bFGF-ir) cells in pars compacta and pars reticulata of 3-, 12- and 26-month-old
      rats were compared. The overall distribution of bFGF-immunoreactivity was similar
      in the three age groups, but changes in the morphological appearance of bFGF-ir
      somata and processes occurred in aging. The results demonstrated a significantly
      reduced number of bFGF-ir cells in pars compacta (by 56.87%) and pars reticulata
      (by 30.4%) in 26-month-old rats compared to 3-month-old rats. The reduction of
      the cell number did not occur smoothly and equally in the two parts of SN. The
      quantitative analysis clearly indicated a significant decrease in the size of
      bFGF-ir neurons in pars compacta (by 18.1%) and pars reticulata (by 14.15%) of 26
      month-old rats compared to 3-month-old rats. Compared to 3-month-old rats, a
      19.77% and 17.83% increase in the staining intensity was observed in the
      remaining bFGF-ir neurons of pars compacta and pars reticulata, respectively in
      26-month-old rats. Since there was no correlation between the decreased size and
      increased staining, it is most probable that the intensification of the staining
      intensity of bFGF-ir neurons was a compensatory response to the cell death.

PMID- 8538247
TI  - The last mitoses of the human fibroblast proliferative life span,
      physiopathologic implications.
AB  - Normal human fibroblasts, after exhausting their proliferative life span, enter a
      post-mitotic stage where they remain metabolically active. It has been suggested
      that this is a terminal differentiation process. During the last mitoses of the
      cell population proliferative life span, sudden events take place in the genome
      consisting of deviations from the semiconservative distribution of DNA between
      sister cells, decondensation of heterochromatin, reorganizations in the high
      order DNA structure and the presence of extrachromosomal circular DNA. These
      events could correspond to the 'quantal mitosis', the last mitosis where cells
      become irreversibly committed to differentiation. The identification of the
      ultrastructural characteristics of the terminal cell allowed for the first time
      to ascertain the presence of these cells in a tissue in vivo. The terminal cell
      obtained through serial proliferation in vitro, was found only in pathological
      states. A cell with some, though not all of the characteristics of the terminal
      in vitro fibroblast, was present in vivo in normal skin in an amount unrelated to
      the age of the donor.

PMID- 8538248
TI  - [Treatment and outcome of pneumococcal meningitis in adults. Study of a recent
      series of 70 episodes].
AB  - BACKGROUND: Pneumococcal meningitis (PM) is an infection with high morbidity and
      mortality. The aim of this study was to evaluate the most relevant clinical,
      epidemiologic and evolutive characteristics of a recent series of adult patients
      with this disease. METHODS: Over a period of 10 years all the patients with PM
      diagnosed by isolation of this microorganism in the cerebrospinal fluid (CSF)
      were evaluated from a clinical, therapeutic and evolutive points of view. The
      impact of the new therapies in the disease and the variables associated with
      mortality were analyzed. RESULTS: Seventy episodes of PM were diagnosed, 60%
      being found in patients over the age of 50 years. The male/female relationship
      was 2/1. Fifty-three percent of the patients had other underlying diseases. Acute
      otitis media (AOM) was the source in 34% of the cases, in 11% the patients had a
      fistula of CSF and in 9% a pneumonia. At the time of diagnosis 74% of the
      patients had some degree of reduction in the level of consciousness and in 40% of
      the episodes the presence of neurologic local manifestations were observed. A
      decrease in sensitivity to penicillin was observed in 33% of the microorganisms
      isolated. Third generation cephalosporins were used as initial treatment in 57
      episodes and penicillin in other 11 episodes. Adjuvant treatment with
      dexamethasone, mannitol and/or diphenylhydantoin was administered in 54% of the
      patients. Overall mortality was 23%: the factors associated with an unfavourable
      evolution were the existence of underlying disease, deep alteration in the level
      of consciousness at the time of diagnosis, the coexistence of pneumonia and the
      absence of adjuvant therapy. CONCLUSIONS: Mortality in pneumococcal meningitis is
      high. The most relevant risk factor is the initial degree of consciousness.
      Adjuvant therapies probably determine a reduction in the rate of mortality.

PMID- 8538250
TI  - [Sexual myths in an adult population].
AB  - BACKGROUND: Clinical observation ratifies the existence of commonly accepted
      erroneous beliefs (EB) in relation to sexuality. In the health care sector,
      reinforcing factors of these beliefs are the professionals who are not
      specifically trained to manage, or detect the same in addition to the variability
      of the criteria available on sexual health care. METHODS: The EB on sexuality
      were studied in 260 individuals (14-18 years) who are users of primary health
      care services. Four consultation offices of General Medicine were randomly
      selected, one by health care center (Area 20, Valencian Community, Spain).
      Subsequently, a structured interview was given to the users of these
      consultations over the period of one day. The interviews were carried out after
      receiving consent and guarantee of confidentiality. On the other hand, the
      results were compared with those previously obtained from the 44 health care
      professionals (HCP). The results are reported, the proportions compared (chi
      square) to determine differences according to age, sex and level of education and
      the odds ratio was calculated to determine the probability of participation in EB
      according to sex. The response rate in users was 97.4% and is HCP 58%. RESULTS:
      The proportion of EB ranged from 16.9% who believed coitus as the only "normal"
      sexual relationship and 63.8% who believed in the existence of two types of
      female orgasm. Depending on the beliefs, statistically significant differences
      were observed according to age (from p = 0.03 to p < 0.0000) and the level of
      education (from p = 0.01 to p < 0.0000) and between the user adult population and
      the HCP (from p = 0.01 to p < 0.0000). CONCLUSIONS: There are numerous erroneous
      beliefs regarding sexuality in both primary health care users and, to a lesser
      extent, Spanish health care professionals. The influence of moral criteria,
      centered on reproduction, and prevalent sociocultural norms and values is of
      note. It was found that erroneous beliefs do not decrease with the educational
      level, but rather, change.

PMID- 8538249
TI  - [Relationship between coffee and blood cholesterol in a sample of working women].
AB  - BACKGROUND: Experimental studies have demonstrated that unfiltered coffee
      increases cholesterolemia. In Spain, filtered coffee is mainly consumed and its
      effect on cholesterolemia is controversial. METHODS: The relationship between
      coffee intake and the serum levels of total cholesterol was transversally studied
      in a population of 609 women between 18 to 65 years in age. The questionnaire and
      analyses were carried out in the context of periodic health examination. RESULTS:
      The consumption of coffee was positively associated with cholesterolemia in
      subjects under 30 years of age (p < 0.01) and in the group from 30 to 45 years in
      age (p < 0.05). This association was found to be statistically significant on
      multivariant analysis (multiple lineal regression) after adjusting for age, body
      mass index, cholesterol consumed in the diet, smoking, alcohol consumption and
      physical activity. CONCLUSIONS: Coffee was found to increase cholesterolemia in
      the female population and therefore a reduction in coffee intake would be
      recommendable in hypercholesterolemic subjects.

PMID- 8538251
TI  - [The need of a registry of HLA-phenotyped platelet donors].

PMID- 8538252
TI  - [Complement inhibition: a new therapeutic modality?].

PMID- 8538253
TI  - [Current status of tuberculosis in Spain. A precarious health care perspective
      with regard to developed countries].

PMID- 8538254
TI  - [Diabetic nephropathy and molecular biology of the renin-angiotensin system in
      the diabetic kidney].

PMID- 8538255
TI  - [Acute hepatitis E in Spain].

PMID- 8538256
TI  - [Atrial fibrillation in lacunar-type cerebral infarction].

PMID- 8538257
TI  - [Sotalol interference in the determination of urinary metanephrine].

PMID- 8538258
TI  - [Aspergillus tracheobronchitis in a patient with AIDS].

PMID- 8538259
TI  - [Endophthalmitis secondary to bacterial endocarditis].

PMID- 8538260
TI  - [Epidemic outbreak of classical heat stroke].

PMID- 8538261
TI  - [Lack of knowledge about previous blood transfusion in young HCV-positive
      patients].

PMID- 8538262
TI  - [Use of hydroxymethylglutaryl coenzyme A reductase inhibitors in patients with
      post-transplantation hyperlipemia].

PMID- 8538263
TI  - XIX National Meeting of the Spanish Society of Pharmacology, Madrid, October 4-6,
      1995. Abstracts.

PMID- 8538264
TI  - [The Malarhospital in Eskilstuna: personal and professional development as part
      of internship].

PMID- 8538266
TI  - [Evaluation of calcium antagonists--a question for the SBU].

PMID- 8538265
TI  - [Free of charge primary health care!].

PMID- 8538267
TI  - [It is wrong to rely on behavioral models only in cases of back- and neck pain].

PMID- 8538268
TI  - [Test screening--a way to find heavy drinkers].

PMID- 8538269
TI  - [Approved implants are not always carefully tested].

PMID- 8538270
TI  - [Rehabilitation of physicians with cooperation problems].

PMID- 8538271
TI  - [Should coffee be classified as a doping agent? Caffeine is definitely effective
      when it comes to performance capacity].

PMID- 8538272
TI  - [Catheter ablation of paroxysmal supraventricular tachycardia in children. Time
      for further indications?].

PMID- 8538273
TI  - [Mass occurrence of trauma in Rwanda. 247 surgical interventions performed by 2
      surgeons during 2 weeks].

PMID- 8538275
TI  - [An Asian congress on endoscopy. "Direct" broadcast of surgery].

PMID- 8538276
TI  - [Diabetes insipidus. A possibly life-threatening condition during anesthesia].

PMID- 8538277
TI  - [From Hiroshima to Chernobyl. Increasing number of late fatal cases of cancer].

PMID- 8538274
TI  - [Good surgical care at a county hospital. Evaluation of 5 years of emergency
      traumatology].

PMID- 8538278
TI  - [Traumatology at small hospitals. Prompt care saves lives].

PMID- 8538279
TI  - [The National Medical Ethics Committee: our data on consequences of IVF (in vitro
      fertilization) are unsatisfactory].

PMID- 8538280
TI  - [A debate on involuntary childlessness. Let us separate the different methods.
      IVF is getting safer].

PMID- 8538281
TI  - [Privately managed IVF (in vitro fertilization) is important and necessary].

PMID- 8538282
TI  - [Old data do not reflect current lower-risk IVF].

PMID- 8538283
TI  - [Final reply on IVF. The good news is that SMER is open for new facts].

PMID- 8538284
TI  - [Continuing education in the Swedish Society of General Practice. A newly
      established secretariat is supported by a committee on a course catalogue and
      pharmacotherapy].

PMID- 8538285
TI  - [Legal rights are threatened by current application of the law. Forensic
      psychiatric care should not serve as detention].

PMID- 8538286
TI  - [Drug abuse testing at work. Not a difficult medical-ethical problem].

PMID- 8538287
TI  - [Information center concerning children with chronic ITP (Idiopathic
      Thrombocytopenic Purpura) is being founded].

PMID- 8538288
TI  - [Rehabilitation pedagogy].

PMID- 8538289
TI  - [Ursodeoxycholic acid in Scandinavian folk medicine].

PMID- 8538291
TI  - [Temperature-directed radiofrequency ablation. A new safer treatment of
      tachycardia].

PMID- 8538290
TI  - [Connection between levonorgestrel-IUD and GAS (Group A Streptococcus) sepsis?
      Reliable risk assessment is not yet possible].

PMID- 8538292
TI  - [Connection between smoking and reduced risk of ulcerative colitis. Does nicotine
      mediate a protective effect?].

PMID- 8538294
TI  - [SBU: bone density measurements in connection with physical check-ups are not
      justified].

PMID- 8538293
TI  - [Possible effect of administration methods on pharmacological action. Study of
      cytostatic therapy in advanced cancer].

PMID- 8538295
TI  - [Should parenteral nutrition be discontinued? An ethical dilemma in terminal
      care].

PMID- 8538296
TI  - [Streetcars in urban environment pose a great risk of accidents].

PMID- 8538297
TI  - [A secondary case of hepatitis E. Since 1990 only one of the 17 imported cases
      was transmitted].

PMID- 8538298
TI  - [Joint hypermobility, skin hyper-elasticity, connective tissue fragility:
      classical symptoms of Ehlers-Danlos syndrome].

PMID- 8538299
TI  - [Licensed general practitioners find obstacles in the access to continued
      education].

PMID- 8538300
TI  - The Hippocratic Oath.

PMID- 8538302
TI  - English HIV and AIDS projections made.

PMID- 8538301
TI  - Inhibition of the mevalonate pathway: benefits beyond cholesterol reduction?

PMID- 8538303
TI  - Danes' AIDS education criticised.

PMID- 8538304
TI  - Indian Supreme Court demands cleaner blood supply.

PMID- 8538305
TI  - Mercury poisoning by vacuum-cleaner aerosol.

PMID- 8538306
TI  - c-ANCA as a marker of Wegener's disease.

PMID- 8538307
TI  - c-ANCA as a marker of Wegener's disease.

PMID- 8538308
TI  - c-ANCA as a marker of Wegener's disease.

PMID- 8538309
TI  - c-ANCA as a marker of Wegener's disease.

PMID- 8538310
TI  - c-ANCA as a marker of Wegener's disease.

PMID- 8538311
TI  - c-ANCA as a marker of Wegener's disease.

PMID- 8538312
TI  - Molecular evidence of transmission of hepatitis B in a day-care centre.

PMID- 8538313
TI  - Hyporeninaemic hypoaldosteronism after growth hormone treatment.

PMID- 8538314
TI  - Treatment of Crohn's disease fistulas with coagulation factor XIII.

PMID- 8538315
TI  - GBV-C in the aetiology of fulminant hepatitis.

PMID- 8538316
TI  - ACAS recommendations for carotid endarterectomy. ACAS Executive Committee.

PMID- 8538317
TI  - Darkroom exposure to hydroquinone.

PMID- 8538318
TI  - HRT and ACE activity in postmenopausal women.

PMID- 8538319
TI  - Premenstrual syndrome.

PMID- 8538320
TI  - Bacterial meningitis and the painful eye.

PMID- 8538321
TI  - Pasteurella multocida from a dog causing Ludwig's angina.

PMID- 8538322
TI  - Crisis for biomedical research in New Zealand.

PMID- 8538323
TI  - The clozapine clinic.

PMID- 8538324
TI  - Economics and the examination room: an incident.

PMID- 8538325
TI  - Adenovirus endocarditis.

PMID- 8538326
TI  - Medical television.

PMID- 8538327
TI  - Medical television.

PMID- 8538328
TI  - Pneumocystis carinii pneumonia in Africa.

PMID- 8538329
TI  - Pneumocystis carinii pneumonia in Africa.

PMID- 8538330
TI  - Efficacy of risperidone in idiopathic segmental dystonia.

PMID- 8538331
TI  - Statin therapy and CHD.

PMID- 8538332
TI  - Intestinal perforation after ingestion of a blister-wrapped tablet.

PMID- 8538333
TI  - Transmission of pertussis: do adults have an important role?

PMID- 8538334
TI  - Mutation analysis of presenillin 1 gene in Alzheimer's disease.

PMID- 8538335
TI  - Spinal epidural haematoma complicating diagnostic lumbar puncture.

PMID- 8538336
TI  - Treatment of strawberry marks with flashlamp-pumped pulsed dye laser in infancy.

PMID- 8538337
TI  - FIRI: fasting or false insulin resistance index?

PMID- 8538338
TI  - Unacceptable solution to US health-care costs.

PMID- 8538339
TI  - Not quite as random as I pretended.

PMID- 8538340
TI  - Pathogenesis of sudden ischaemic cardiac death.

PMID- 8538341
TI  - HIV quantification: clinical applications.

PMID- 8538342
TI  - Why flush?

PMID- 8538343
TI  - Umbilical cord prolapse: so far so good?

PMID- 8538344
TI  - Prospective controlled study of endoscopic ultrasonography and endoscopic
      retrograde cholangiography in patients with suspected common-bileduct lithiasis.
AB  - BACKGROUND: Endoscopic sphincterotomy is sometimes done unnecessarily in patients
      with suspected choledocholithiasis. Our aims were to assess the diagnostic
      accuracy of endoscopic ultrasonography and endoscopic retrograde cholangiography
      (ERC) and to find out whether endoscopic ultrasonography may help to prevent
      unnecessary sphincterotomy or surgical explorations. METHODS: We recruited 119
      patients aged 70.4 (SD 16.1) years with strongly suspected choledocholithiasis
      who presented to our endoscopy unit between January, 1994, and January, 1995.
      During the same spell of sedation or within 2 h of each other, endoscopic
      ultrasonography and ERC were carried out by investigators unaware of the
      patient's history. Endoscopic sphincterotomy with instrumental exploration was
      then done as the gold standard for the presence or the absence of stones.
      FINDINGS: 78 (66%) patients had choledocholithiasis; 17 (14%) had other bileduct
      diseases; 24 (20%) had a clear bileduct or did not require an invasive endoscopic
      procedure. The sensitivity of endoscopic ultrasonography was 93%, specificity
      97%, positive predictive value 98%, and negative predictive value 88%. The
      corresponding values for ERC were 89%, 100%, 100%, and 83%. There were five false
      negative cases by endoscopic ultrasonography (of which three were also negative
      with ERC) and one false-positive. The morbidity rate was 4.1%. INTERPRETATION: We
      conclude that endoscopic ultrasonography is at least as sensitive as ERC.
      Endoscopic ultrasonography may prevent inappropriate invasive explorations of the
      common bileduct.

PMID- 8538345
TI  - Randomised trial of excimer laser angioplasty versus balloon angioplasty for
      treatment of obstructive coronary artery disease.
AB  - BACKGROUND: Excimer laser coronary angioplasty is reported to give excellent
      procedural results for treatment of complex coronary lesions, but this method has
      not been compared with balloon angioplasty in a randomised trial. METHODS:
      Patients (n = 308) with stable angina and coronary lesions longer than 10 mm on
      visual assessment were included. 151 patients (158 lesions) were assigned
      randomly to laser angioplasty and 157 (167 lesions) to balloon angioplasty. The
      primary clinical endpoints were death, myocardial infarction, coronary bypass
      surgery, or repeat coronary angioplasty of the randomised segment during 6 months
      of follow-up. The primary angiographic endpoint was the minimal lumen diameter at
      follow-up in relation to the baseline value (net gain), as determined by
      quantitative coronary angiography. FINDINGS: Laser angioplasty was followed by
      balloon angioplasty in 98% of procedures. The angiographic success rate was 80%
      in patients treated with laser angioplasty compared with 79% in patients treated
      with balloon angioplasty. There were no deaths. Myocardial infarction, coronary
      bypass surgery, and repeat angioplasty occurred in 4.6%, 10.6%, and 21.2%,
      respectively, of the patients in the laser angioplasty group compared with 5.7%,
      10.8%, and 18.5% of the balloon angioplasty group. Net mean (SD) gain in minimal
      lumen diameter was 0.40 (0.69) mm in patients treated with laser angioplasty and
      0.48 (0.66) mm in those treated with balloon angioplasty (p = 0.34). The
      restenosis rate (> 50% diameter stenosis) was 51.6% in the laser angioplasty
      group versus 41.3% in the balloon angioplasty group (p = 0.13). INTERPRETATION:
      Excimer laser angioplasty followed by balloon angioplasty provides no benefit
      additional to balloon angioplasty alone with respect to the initial and long-term
      clinical and angiographic outcome in the treatment of obstructive coronary artery
      disease.

PMID- 8538346
TI  - Prognostic implications of fetal echogenic bowel.
AB  - BACKGROUND: An increased frequency of hyperechogenic bowel on ultrasound has been
      reported in fetuses with cystic fibrosis (CF) and trisomy-21. However, the
      diagnostic application of this observation has been hampered by the absence of a
      means of measuring echogenicity. METHODS: We devised an ultrasonic grading system
      in which echogenicity was quantified by linear gain reduction and comparison with
      fetal iliac crest. From 7400 second-trimester ultrasound referrals, 145 patients
      were identified as having a fetus with abnormally echogenic bowel. They were
      offered genetic counselling, parental and (if appropriate) CF carrier testing,
      and amniocentesis for karyotype and CF status if parents were informative. Follow
      up was to 4 months of age. FINDINGS: Of 40 fetuses with mild increase in bowel
      sonodensity (grade 1), none had CF or aneuploidy. Of 81 patients identified with
      a moderate increase (grade 2), 2 had trisomy 21 and 2 had CF. And of 24
      pregnancies with a pronounced increase (grade 3), 5 had CF and 6 had trisomy-21.
      INTERPRETATION: Parental CF carrier testing and amniocentesis to identify
      aneuploidy or fetal CF status has a high positive ascertainment rate in fetuses
      with echogenic bowel grades 2 and 3.

PMID- 8538347
TI  - Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation
      of the 11 beta-hydroxysteroid dehydrogenase type 2 gene.
AB  - BACKGROUND: 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the
      interconversion of hormonally active cortisol to inactive cortisone and is vital
      for dictating specificity for the mineralocorticoid receptor. Thus, in patients
      with congenital deficiency of 11 beta-HSD (the syndrome of apparent
      mineralocorticoid excess, AME), cortisol and not aldosterone acts as a
      mineralocorticoid, resulting in hypertension and hypokalaemia with suppression of
      the renin-angiotensin-aldosterone axis. Two isoforms of human 11 beta-HSD have
      been described, but it is the NAD-dependent type 2 isoform (11 beta-HSD2), first
      characterised in placental tissue, that is expressed in the mineralocorticoid
      target tissues, kidney and colon. We have analysed the 11 beta-HSD2 gene as a
      candidate gene in explaining the molecular basis of AME. METHODS: By exon
      specific PCR-amplification of the 11 beta-HSD2 gene in a consanguineous kindred
      with AME, we found a point mutation (C1228T) in two affected siblings, and also
      in placental DNA obtained from a stillbirth pregnancy. FINDINGS: The mutation in
      exon 5 of the 11 beta-HSD2 gene resulted in a premature stop site at codon 374
      instead of a normal arginine (R374X), with the deletion of 32 aminoacids from the
      C-terminus of the 11 beta-HSD2 enzyme protein. Both parents, who are
      phenotypically normal, are heterozygote for the C1228T mutation in keeping with
      an autosomal recessive form of inheritance. NAD-dependent 11 beta-HSD activity
      was severely attenuated in the stillbirth placenta compared with control
      placental tissue, and no 11 beta-HSD immunostaining was observed in this placenta
      with antisera derived against a C-terminal 11 beta-HSD2 peptide sequence.
      INTERPRETATION: AME is due to a mutation in the 11 beta-HSD2 gene, and is an
      example of human hypertension arising from a single gene defect.

PMID- 8538348
TI  - Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C
      virus.
AB  - BACKGROUND: Fulminant hepatitis on withdrawal of chemotherapy has been described
      in chronic hepatitis B virus infection, but not in hepatitis C virus (HCV)
      infection. The relation between HCV and immune response to this virus, and
      disease severity, has not been examined. We present two patients with HCV who
      developed fulminant liver failure after chemotherapy was stopped. PATIENTS AND
      FINDINGS: Two patients with chronic HCV infection and malignant lymphoma received
      chemotherapy (cyclophosphamide, adriamycin, vincristine, bleomycin, etoposide,
      and prednisolone in patient 1; doxorubicin, bleomycin, vinblastine, and
      dacarbazine in patient 2), on withdrawal of which both developed fulminant
      hepatitis. Alanine aminotransferase (ALT) concentrations were greatly raised
      (6030 and 3870 IU/L in patients 1 and 2, respectively), and serum HCV-RNA was low
      in both patients when severe disease developed (10(2) genome equivalents per mL).
      Patient 1 died, and necropsy showed massive liver necrosis. INTERPRETATION: The
      findings suggest an immune-mediated mechanism for hepatocyte damage in HCV
      infection. Careful monitoring of ALT concentrations is necessary in such patients
      during and after chemotherapy.

PMID- 8538349
TI  - Association between angiotensin-converting-enzyme gene polymorphism and failure
      of renoprotective therapy.
AB  - BACKGROUND: Polymorphism in the gene for angiotensin-converting enzyme (ACE),
      especially the DD genotype, is associated with risk for cardiovascular disease.
      Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene
      polymorphism in patients with kidney disease who were in a trial of long-term
      therapy with an ACE inhibitor or a beta-blocker. METHODS: 81 patients with non
      diabetic renal disease had been entered into a randomised comparison of oral
      atenolol or enalapril to prevent progressive decline in renal function. The dose
      was titrated to a goal diastolic blood pressure of 10 mm Hg below baseline and/or
      below 95 mm Hg. The mean (SE) age was 50 (1) years, and the group included 49
      men. Their renal function had been monitored over 3-4 years. We have looked at
      their ACE genotype, which we assessed with PCR. FINDINGS: 27 patients had the II
      genotype, 37 were ID, and 17 were DD. 11 patients were lost to follow-up over 1-3
      years. The decline of glomerular filtration rate over the years was significantly
      steeper in the DD group than in the ID and the II groups (p = 0.02; means -3.79, 
      1.37, and -1.12 mL/min per year, respectively). The DD patients treated with
      enalapril fared as equally a bad course as the DD patients treated with atenolol.
      Neither drug lowered the degree of proteinuria in the DD group. INTERPRETATION:
      Our data show that patients with the DD genotype are resistant to commonly
      advocated renoprotective therapy.

PMID- 8538350
TI  - A labourer with a spot on his chest.

PMID- 8538351
TI  - Are detoxification programmes effective?

PMID- 8538352
TI  - Holmium:YAG laser endoscopic sinus surgery: a randomized, controlled study.
AB  - Although surgical lasers were introduced to the field of otolaryngology more than
      20 years ago, their use in rhinologic surgery has remained relatively limited.
      With the development of the holmium:yttrium-aluminum-garnet (YAG) laser, a device
      is now available that offers those features necessary for effective sinus
      surgery:precise bone ablation, efficient soft tissue coagulation, and fiberoptic
      transmission. This solid-state laser of 2.1-microns wavelength can be coupled
      with endoscopic instrumentation for the surgical treatment of sinus disease. This
      study was conducted to determine the clinical efficacy of the holmium:YAG laser
      for endoscopic sinus surgery. A microscopic analysis of laser-treated sinus
      tissue was also performed in an attempt to determine the histologic basis of the
      observed clinical findings. In a prospective, randomized, controlled, single
      blinded study, 32 consecutive patients underwent endoscopic sinus surgery using
      the holmium:YAG laser on one side of the nose and conventional endoscopic
      instrumentation on the other side. Patients rated symptoms for each side of the
      nose at 1 week, 1 month, 3 months, 6 months, and 2 years after surgery. Healing
      parameters were similarly rated by the surgeon. Until the study was completed,
      patients were not told which side of the nose had been treated with laser
      surgery. No intraoperative complications occurred. The mean intraoperative blood
      loss was 24.6 mL less on the laser-treated side of the nose than on
      conventionally treated side (P < .001). At 1 week after surgery, there was
      increased mucosal edema on the laser-treated side (P < .01). Crust formation was
      greater on the conventionally treated side at 1 week and was greater on the laser
      treated side at 1 mouth (P < .01). Improvements in symptoms of pain, congestion,
      and drainage were equivalent for both treatment modalities (P < .001).
      Microscopic analysis demonstrated the ability of the holmium:YAG laser to remove
      tissue in relatively thin layers with ablation depths of 260 +/- 8.2 microns, 286
      +/- 9.4 microns, and 341 +/- 20.4 microns per pulse at energy levels of 0.5, 1.0,
      and 1.5 J, respectively. A zone of thermal necrosis extending up to 1 mm beyond
      the site of laser impact was thought to correlate with the increased
      postoperative edema observed on the laser-treated side. Endoscopic sinus surgery
      with the holmium:YAG laser is as effective as nonlaser techniques in relieving
      the symptoms of chronic sinusitis. Laser surgery offers improved intraoperative
      hemostasis, but it causes increased postoperative tissue edema. The holmium:YAG
      laser provides the surgeon with an additional tool for the performance of safe,
      effective sinus surgery.

PMID- 8538353
TI  - [Anterior septal myocardial infarct impairs cardiovascular function more than
      inferior septal myocardial infarct].

PMID- 8538354
TI  - [Occurrence of retinopathy of prematurity at the Koprivnica Hospital during 2 5
      year periods].
AB  - The prevalence of retinopathy of prematurity (ROP) in the Koprivnica General
      Hospital among infants weighting < or = 1500 g at birth and with < or = 31 weeks
      of gestation, increased in the second of the two five-year periods (I 1984-1988
      and II 1989-1993). In period I only one infant with ROP in stage 4 was diagnosed
      during hospitalization. In period II prevalence of ROP in infants with birth
      weight < or = 1500 g was 56.5% and in newborns whose gestational age was < or =
      31 weeks it was 28.9%. The ROP group of infants had significantly lower birth
      weight and gestational age. Oxygen therapy and duration of stay in the incubator
      were significantly longer in the ROP group. Apneic spells and blood transfusions
      were more frequent in the ROP group of infants. Mortality of premature infants
      during period II was significantly lower (chi 2 = 5.95; P = 0.015), while the
      number of fundus examinations in the hospital significantly increased (chi 2 =
      36.4; P = 1.7 x 10(-9)). In period II 7 of 13 premature infants had ROP stage 1
      or 2, and 6 of them had ROP stage 3 according to the international classification
      of ROP. Premature infants with ROP stage 3 had significantly lower birth weights
      (Z = 1.86; P = 0.032) as well as gestational ages (Z = 1.71; P = 0.04), compared
      to premature infants with ROP stage 1 or 2. All ocular changes regressed
      spontaneously in infants with ROP stage 1 or 2. Outcome in infants with ROP stage
      3 was as follows: 5 eyes were blind, changes regressed spontaneously in 4 eyes,
      while regression occurred after transconjunctival cryotherapy in 3 eyes.

PMID- 8538355
TI  - [Ventricular extrasystole in comparison with manifestations of ventricular
      tachycardia and ventricular fibrillation in acute myocardial infarct]].
AB  - We studied 76 patients with first recent myocardial infarction being not older
      than 12 hours. The patients included 58 men and 18 women. Their mean age was 62
      years. We recorded continuously during the first three days following infarction
      the heart rate, all forms of ventricular premature beats, ventricular
      tachycardia, ventricular fibrillation, clinical status and activity of creatinine
      phosphokinase and its isoenzyme MB. The results showed that ventricular premature
      beats (coupled and multiform) as well as ventricular tachycardia were more
      frequent in the first day of illness, while ventricular premature beats (except
      bigeminy, for which there is no explanation) were infrequent in the second and
      the third day after development of an infarct. The incidence of ventricular
      tachycardia during the follow-up period did not differ significantly. Ventricular
      fibrillation developed in 7 patients (9.2%). A comparison of the relation between
      ventricular premature beats and malignant ventricular tachycardia, i.e.
      ventricular tachycardia and ventricular fibrillation, revealed that the patients
      with more frequent ventricular tachycardia usually had frequent ventricular
      premature beats, particularly more often bigeminy, trigeminy, polymorphous
      ventricular premature and coupled ventricular premature beats, but not
      ventricular premature beats with R-on-T phenomenon. Ventricular tachycardia,
      however, was also found in patients with an evidence of more rare ventricular
      premature beats. This suggests that the occurrence of aforementioned forms of
      ventricular premature beats denotes only a somewhat greater probability that
      ventricular tachycardia will occur. The fact that there is a lack of correlation
      between ventricular tachycardia and R-on-T phenomenon indicates that this
      probability is not so significant. In conclusion, the authors believe that the
      patients with recent myocardial infarction and ventricular premature beats should
      be adequately followed up, and that prophylactic antiarrhythmic therapy is not
      required in most cases, as it was previously widely accepted concept. It should
      be administered only when ventricular tachycardia develops. Patients with
      ventricular fibrillation had more frequent ventricular premature beats, although
      ventricular premature beats in these patients were not statistically more
      frequent from those found in the patients in whom ventricular fibrillation was
      not verified. The presence or absence of ventricular tachycardia and ventricular
      fibrillation, respectively, had no influence on the other followed up parameters.

PMID- 8538356
TI  - [Determination of antibody kinetics in Mediterranean spotted fever using the Weil
      Felix agglutination test, complement fixation and indirect immunofluorescence].
AB  - The kinetics of antibodies in human cases of Mediterranean spotted fever was
      studied by applying Weil-Felix (WF) agglutination with Proteus OX antigens,
      complement fixation (CF) and indirect immunofluorescence (IF) tests with
      Rickettsia conorri antigen to 46 sera from 21 patients. The kinetics of specific
      (CF and IF) and nonspecific (WF) antibodies was similar. The percentage of the
      positive sera and geometric mean titers of antibodies reached the maximum after
      14 days from the onset of illness.

PMID- 8538357
TI  - [Comparison of intradermal and prick tests based on samples of the most common
      allergens in the Zadar region].
AB  - The practical clinical problem of evaluating the significance of positive dermal
      tests is present in daily in vivo diagnoses in allergology and clinical
      immunology. Our research was aimed at a comparison of the two methods of dermal
      tests, namely, intradermal (i.d.) and prick tests, based on a sample of the most
      common allergenics in the Zadar region. The intradermal method was applied to a
      group of 664 patients, the prick test was used in a group of 641 patients, and 60
      patients were examined using both methods. In the tests allergens from extracts
      of Dermatophagoides pteronyssinus, tree, weeds and grass pollens, dust, feathers,
      eggs, milk, flour, meat and fish from the Zagreb Institute of Immunology were
      used. A solution of histamine chloride and buffer saline containing 50% glycerol,
      prepared by the same Institute was used as a control. We considered a positive
      reaction to the intradermal test to have occurred when an urticaria of 5 or more
      mm radius with surrounding inflammation developed. A reaction to the prick method
      was considered to have taken place when an urticaria of 3 or more mm radius,
      together with surrounding inflammation resulted. A positive reaction was shown in
      30% of those to whom the prick test was applied, and in 32% of those to whom
      intradermal tests were used, which represents 0.11-0.13% of the total adult
      population of the region of Zadar. A positive reaction to a single allergen was
      shown in 43% of the patients tested by i.d. test, and in 52% of the patients
      tested with the prick method. The most common oversensitivity with both methods
      was shown to Dermatophagoides pteronyssinus (86% i.d., and 56% prick,
      respectively). Among the pollen allergenics the most common reaction was to grass
      pollen (47% i.d., 65% prick). With patients who were tested with both methods (60
      patients), there were also differences in results. An equal dermal reaction to
      both tests was shown in 32% of the patients, minor differences were present in
      45%, and significant differences occurred with 23% of the patients. Regarding
      Dermatophagoides pteronyssinus, it is shown that the positive dermal reaction was
      statistically significantly larger with patients tested with i.d. than when the
      prick test was used (chi 2 = 17.39, p < 0.05). There was no statistically
      significant difference between the two methods regarding the allergenics of
      pollen and feather. These results lead to the conclusion that it is necessary to
      uniform the conditions for allergological tests. This implies the use of
      standardized allergenic preparations of similar concentrations, the selection of
      a uniform method and technique for testing, and compliance with other relevant
      factors.

PMID- 8538358
TI  - [Q-fever in the Zadar region].
AB  - The occurrence of Q fever in a population of Zadar region (2787 km2) which has
      five microregions (Zadar, Benkovac, Biograd, Obrovac and Pag microregion) is
      presented. In 1986, nine cases of Q fever were reported. Five patients were
      detected in Zadar community, one in Pag microregion and 3 in Biograd community
      and microregion, respectively. In 1989, two cases in Zadar and, in 1988 and 1991,
      one case in each year from the territory of Zadar were found. A total of 13 cases
      of Q fever were treated and reported. The personnel of the Zadar Veterinary
      Stations were not able to provide information since blood samples from the
      suspected animals were not taken. The agent was therefore not isolated. It is
      known that there were more serologically proven cases of Q fever, but they were
      not registered by the Epidemiologic Service of the Zadar Department for Health
      Protection. Clinical manifestation in a form of pulmonary affection is a very
      significant data in this zoonosis and it is therefore most commonly detected at
      the hospital departments for lung diseases, what was one of the reasons for
      undertaking this study.

PMID- 8538359
TI  - [Psychiatry--where are we and where are we going?].
AB  - The article gives a short review of the historical, ideological, theoretical and
      organizational development of the concept of protection and improvement of mental
      health (within a psychiatric context) both in Croatia and the rest of the world
      with special emphasis on the problems and possibilities which arise from the
      present situation in Croatia. It also explains the necessity to analyze the Law
      on Health Care and Health Insurance from a psychiatric point of view, the need to
      link the areas of psychiatry (preventive and clinical work) which deal with
      primary protection, the need to define the criteria and standards regarding the
      organization and reorganization of psychiatric clinics and general hospitals, the
      need to analyze and reorganize the study of psychiatry, the need to establish
      national and regional coordination boards and hold elections for national and
      regional coordinators and the need to establish the Centre for the Protected and
      Improvement of Mental Health.

PMID- 8538360
TI  - [Problems in adolescents and adults with congenital heart defects].
AB  - The first palliative operations of congenital heart disease in the 1940s and
      1950s, and then open heart surgery in the 1960s, have resulted in survival of
      patients whose follow-up is now over 30 years. Problems of patients with
      congenital heart disease are cardiac (pulmonary hypertension, systemic
      hypertension, dysrhythmias, endocarditis, cerebral insults, etc.), and noncardiac
      (scoliosis, intrathoracic adhesions, cosmetic problems, pregnancy, physical
      activity, employment, etc.). A pediatric cardiologist usually follows up such
      patients until adolescence, however, after that time they remain without
      physician's care who followed them in their childhood, being transferred for
      further controls and follow-up to internists-cardiologists. Many difficulties
      arise since internists-cardiologists are not properly trained in this particular
      sense, and pediatricians are not trained to follow-up adult patients. The care
      for a patient should be coordinated. To care for an adolescent, who was the child
      with congenital heart disease, pediatrician and cardiologist have to work at the
      same medical centre. The follow-up should continue as a team work, in which,
      besides pediatrician and cardiologists, cardiosurgeon, psychologist,
      psychiatrist, obstetrician, specialist for physical medicine and social worker
      should be included. A correction of educational plan is mandatory.

PMID- 8538361
TI  - [The Temple of Aesculapius in Diocletian's palace in Split].
AB  - Many temples, sanctuaries and even the entire small towns have been dedicated to
      Aesculapius's, the god of medicine. The remnants of Aesculapius temples in the
      Republic of Croatia have been found on locations of Narona, Salona, Pola and in
      Diocletian's palace in Split. The first archbishop of Split, "Giovanni di
      Ravenna", at the end of the 8th century or at the beginning of the 9th century,
      gave to Diocletian's Mausoleum the name of "Templum Jouis" and reassigned it to
      Christian church. Thomas the Archdeacon in the 13th century mentioned three
      temples in Diocletian's Palace: "templa...Jouis, Asclepii, Martis", while in 1567
      Antonio Proculiano described four temples: the octogonal temple on the east
      dedicated to Jupiter (the present cathedral), the rectangular temple on the west
      (the present baptistry), a minor round temple on the south and a round-hexagonal
      temple on the north. The majority of authors, for centuries, called the
      baptistry: Aesculapius's temple, while only a few others called it Jupiter's or
      Janu's temple. It seems logical to assume that there was only one Jupiter's
      temple in Diocletian's Palace, namely the present cathedral. Four cultic edifices
      within the Diocletian's Palace were given six names: "Jouis, Asclepii, Martis,
      Janus's Kibela's and Venus's. Should the recent research prove the baptistry not
      to be Aesculapius's temple, the question might be raised whether one of the two,
      recently discovered small temples, Kibela's or Venus's, was dedicated to
      Aesculapius?

PMID- 8538362
TI  - Behavioral effects of MK-801 in morphine-dependent and non-dependent mice.
AB  - The behavioral effects of MK-801 were compared in morphine-dependent and non
      dependent mice. The dose of MK-801 selected for these studies was previously
      demonstrated to attenuate some of the morphine withdrawal signs. Subjects were
      repeatedly exposed to morphine (8 days, b.i.d., 10-100 mg/kg, s.c.). Twenty-four
      hours after last morphine injection mice received naloxone (0.1 mg/kg, s.c.) and
      the observation was commenced. Animals were pretreated with either MK-801 (0.1
      mg/kg, i.p.) or saline 30 min prior to testing. It was found that the behavioral
      effects of MK-801 (decreased sociability, and increased rate of transitions
      between behavioral elements, locomotion, grooming) were less pronounced in
      morphine-dependent compared to non-dependent subjects. However, the intensified
      almost stereotypic eating possibly reflected increased psychotomimetic potency of
      MK-801 in morphine-withdrawn animals.

PMID- 8538363
TI  - Neurochemical correlates of antiepileptic drugs in the genetically epilepsy-prone
      rat (GEPR).
AB  - The GEPR model is composed of two independently derived strains of rats each
      characterized by a broad-based seizure predisposition. Moderate seizure GEPRs
      (GEPR-3s) exhibit generalized clonus with loss of righting reflex in response to
      a standardized sound stimulus. The same stimulus in severe seizure GEPRs (GEPR
      9s) produces a tonic-clonic convulsion much like that produced by supramaximal
      electroshock. The numeric descriptors (3 and 9) derive from the ordinal rating
      scale developed by Jobe and coworkers for evaluation of convulsion intensity.
      GEPRs experience an anticonvulsant effect in response to all established and many
      experimental antiepileptic drugs and distinctions between the classes of drugs
      can be made. Since serotonin plays an anticonvulsant role in nearly all animal
      seizure models, we examined the effects of antiepileptic drugs on serotonin using
      microdialysis. Among clinically effective anticonvulsants, carbamazepine,
      antiepilepsirine (used in China) and loreclezole produced dose-related
      anticonvulsant effects and increases in extracellular serotonin in GEPRs.
      Similarly, drugs known to block serotonin reuptake and increase extracellular
      serotonin (fluoxetine and sertraline) produce dose related anticonvulsant effects
      in GEPRs and other animal models. Accentuation of serotonin release by treating
      GEPRs with fluoxetine and 5-hydroxytryptophan enhances the anticonvulsant effect
      produced by fluoxetine. Depletion of serotonin greatly decreased the
      anticonvulsant effect produced by carbamazepine, antiepilepsirine and fluoxetine.
      Phenytoin produced a dose related anticonvulsant effect in GEPRs but did not
      increase extracellular serotonin. Depletion of serotonin did not diminish the
      anticonvulsant effect produced by phenytoin. Thus, serotonin appears to play a
      role in the anticonvulsant effect of several but not all anticonvulsant drugs.

PMID- 8538364
TI  - Enhancement and inhibition of mitogenic action of insulin-like growth factor I by
      high glucose in cultured bovine retinal pericytes.
AB  - To explore the possible relationship between insulin-like growth factor I(IGF-I)
      and diabetic retinopathy, we examined the effects of glucose on IGF-I stimulated
      thymidine incorporation into DNA and IGF-I binding in cultured bovine retinal
      pericytes. IGF-I significantly increased thymidine incorporation, and its effect
      was completely inhibited by IGF-I receptor antibody. The exposure to high glucose
      for 8 h significantly enhanced the IGF-I induced increase in thymidine
      incorporation as compared with those to normal glucose and to high osmolarity. In
      contrast, the incubation with high glucose for 24 h decreased thymidine
      incorporation in response to IGF-I. Specific binding of IGF-I to pericytes was
      increased by the incubation with high glucose for both 8 and 24 h. These results
      suggest that glucose may play an important role in the regulation of mitogenic
      action of IGF-I in retinal pericytes.

PMID- 8538365
TI  - Differential regulation of the murine ribosomal protein L26 gene in macrophage
      activation.
AB  - In mouse RAW 264.7 macrophages, the gene for ribosomal protein L26 is positively
      regulated by silica. In order to study L26 gene expression a near full-length
      cDNA for mouse L26 was isolated and characterized. Sequence analysis revealed
      that mouse L26 is a 145 amino acid protein highly homologous to other vertebrate
      L26 proteins. The treatment of RAW 264.7 cells with the inflammatory mediators
      LPS and IFN gamma induced the expression of L26 mRNA, but the patterns of
      expression obtained differed markedly from silica. On the contrary, TNF alpha
      acted as a down-regulator of L26 gene. Our results suggest that the synthesis of
      ribosomal components in response to macrophage activators is inducer-specific.
      Mouse genomic DNA analysis revealed the presence of multiple (10-12) sequences
      related to the L26 gene.

PMID- 8538366
TI  - Chronic imipramine treatment induces downregulation of alpha-2 receptors in rat's
      locus coeruleus and A2 region of the tractus solitarius.
AB  - Imipramine is an effective antidepressant agent that blocks the reuptake of
      monoamines. In order to understand some of its basic mechanisms of action, we
      investigated the effects of chronic imipramine administration (10 mg/kg, i.p.; 21
      days) on the alpha-2 receptor population of several brain sites. Alpha-2 receptor
      density was estimated by in vitro autoradiography using [3H]Idazoxan. The
      densitometric analysis revealed a decreased receptor density in the A2 region of
      the tractus solitarius (20%) and locus coeruleus (16%). No changes were observed
      in the amygdala, pyriform cortex, periacueductal gray and the bed nucleus of the
      stria terminalis. These results suggest that chronic imipramine treatment
      selectively modulates the alpha-2 receptor population localized in the brain stem
      norepinephrine-rich nuclei and not in the population present on limbic structures
      innervated by noradrenergic terminal projections. The possible physiological
      consequences of this selective modulation of alpha-2 receptors are discussed.

PMID- 8538367
TI  - Down-regulation of adhesion receptors on cells of primate embryos as a probable
      mechanism of the teratogenic action of thalidomide.
AB  - In spite of ongoing speculation, there has been no evidence that adhesion
      receptors are expressed on the cells of mammalian embryos. In this report, we
      provide the first proof that a variety of such receptor (beta 1-, beta 2-, and
      beta 3-integrins and selectin) are indeed expressed on cells of essentially all
      primordia of marmoset embryos at early organogenesis (developmental stages 11 to
      13, or even earlier). Treatment with low doses (20 or as little as 1 mg/kg body
      weight) of a highly teratogenic derivative (EM12) of thalidomide, the most
      notorious human teratogen, triggers a dramatic and statistically highly
      significant down-regulation of several surface adhesion receptors (e.g.
      CD11a/CD18, CD49d/CD29, CD61, etc.) on early limb bud cells and on cells of some
      other primordia during early organogenesis of embryos of a primate (marmoset,
      Callithrix jacchus). Some of these receptors almost disappear, or they are
      expressed at a lower epitope density in the exposed embryos. These down
      regulations of surface adhesion receptors may be expected to alter cell-cell- and
      cell-extracellular matrix interactions, and they are suggested to be a long
      sought primary mechanism of the teratogenic action of thalidomide-type
      substances.

PMID- 8538368
TI  - Cross-reactivity of antihuman monoclonal antibodies with cell surface receptors
      in the common marmoset.
AB  - In this report we demonstrate that a large number of monoclonal antibodies (mAbs)
      against human epitopes cross-react with surface receptors on white blood cells of
      Callithrix jacchus, indicating species similarities. However, a variety of other
      mAbs do not exhibit any cross-reactivity, thus also providing evidence for
      distinct differences in the structure of these receptors among nonhuman primates.
      Such differences have to be known and taken into consideration when attempting
      extrapolations between species. The results presented provide the prerequisite
      for performing extensive studies on immunological structures and functions in
      marmosets under normal and pathological conditions. We conclude that the immune
      system of Callithrix jacchus is a convenient model for studies on immunotoxicity
      with relevance for man, and for this purpose it is clearly superior to that of
      any rodent species.

PMID- 8538369
TI  - Tissue distribution after a single subcutaneous administration of 2,3,7,8
      tetrabromodibenzo-p-dioxin in comparison with toxicokinetics of 2,3,7,8
      tetrachlorodibenzo-p-dioxin in female Wistar rats.
AB  - Tissue concentrations of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) and induction
      of ethoxyresorufin O-deethylase (EROD) were determined in female Wistar rats
      following a single subcutaneous (s.c.) injection of TBDD. Two sets of experiments
      were performed in order to study (a) the time course after a single s.c.
      administration of 600 ng TBDD/kg body wt up to 78 days, and (b) the dose-response
      seven days after a single s.c. injection of different doses of TBDD (3 to 3,000
      ng/kg body wt). The results obtained on toxicokinetics and enzyme induction were
      compared with those following a single s.c. administration of 300 ng/kg body wt
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Three days after the injection,
      approximately 93% of TBDD and 90% of TCDD had been absorbed. Fourteen days after
      s.c. injection less than 1% of the administered dose of both substances remained
      at the injection site. Three days after a single s.c. injection of 600 ng TBDD/kg
      body wt and 300 ng TCDD/kg body wt, the maximum tissue concentrations in the
      liver amounted to (M +/- S.D.) 5.7 +/- 0.8 and 4.7 +/- 0.9 ng/g wet weight,
      respectively. In adipose tissue, the peak concentration was 3.2 +/- 0.2 ng/g wet
      weight for TBDD on day 14, and 0.8 +/- 0.1 ng/g for TCDD on day 7. Throughout the
      study, the concentration ratio in the TCDD-treated group was always at least
      twice as high as that in the TBDD-treated group. The elimination half-life (t1/2)
      of TBDD and of TCDD in the liver was 13.3 and 13.6 days, respectively. In the
      adipose tissue the t1/2 of TCDD was 24.5 days but no reliable t1/2 could be
      calculated for TBDD (t1/2 = 39.4 days with a 95% confidence interval of 25.9 to
      82.4 days). Tissue content of TBDD and TCDD in liver and adipose tissue increased
      dose-dependently, and the linear regression in a double-logarithmic plot showed a
      straight line. Time course of the induction of hepatic EROD activity after
      treatment with 600 ng TBDD/kg body wt was almost identical with that observed
      following a single dose of 300 ng TCDD/kg body wt. The induction of hepatic EROD
      activity was linearly correlated in a double-logarithmic plot to the hepatic
      concentrations of the congeners (both TBDD and TCDD). The slopes of the dose
      response curves after administration of TBDD and TCDD were almost parallel for
      tissue concentrations ranging from 0.1 to 30 ng/g wet weight.

PMID- 8538370
TI  - Thalidomide derivatives and the immune system. 6. Effects of two derivatives with
      no obvious teratogenic potency on the pattern of integrins and other surface
      receptors on blood cells of marmosets.
AB  - The two thalidomide (Thd) derivatives beta-EM12 and phthalimidophthalimide
      (Phtpht), which exhibit no obvious teratogenicity, were tested for their ability
      to induce changes in the pattern of lymphocyte subpopulations, and especially
      changes in integrin receptors, in marmosets (Callithrix jacchus). Previously, Thd
      and its highly teratogenic derivative alpha-EM12 had been found to alter the
      expression of adhesion molecules, such as CD2 (LFA-2) or CD11a/CD18 (LFA-1). None
      of these typical effects on adhesion receptors were observed following
      administration of the relatively high daily doses of 50 mg/kg body wt beta-EM12
      and Phtpht. Nevertheless, there were some minor effects, such as alterations in
      the receptor density on peripheral blood mononuclear cells, which were often
      contrary to the effects induced by Thd. Mainly affected were: CD8 cells, B cells
      bearing the CD54 receptor and CD4 cells bearing the CD56 (NCAM) surface marker.
      We observed an increase in the receptor density of CD11c (p150,95) on monocytes
      with Phtpht but not with beta-EM12. The inability of the two substances with no
      obvious teratogenic potential to typically modify beta 2-integrin receptors on
      white blood cells at comparatively high doses is consistent with our hypothesis,
      that the teratogenicity of Thd may also be linked to alterations in the
      expression of adhesion molecules.

PMID- 8538371
TI  - Diazepam pretreatment suppresses morphine withdrawal signs in the mouse.
AB  - The effect of diazepam on the development of physical dependence on morphine and
      on the naloxone-precipitated increase in cortical NA turnover were investigated
      in mice. Co-administration of diazepam (1-4 mg/kg, i.p.) during chronic morphine
      treatment suppressed the expression of naloxone (3 mg/kg, s.c.)-precipitated
      withdrawal signs (jumping, exploratory rearing and weight loss). However, a
      single injection of diazepam (4 mg/kg, i.p.) in morphine-dependent mice did not
      affect the expression of naloxone-precipitated withdrawal signs. The 3-methoxy-4
      hydroxyphenylethyleneglycol (MHPG) level and noradrenaline (NA) turnover
      (MHPG/NA) in the cerebral cortex were increased by naloxone (3 mg/kg) challenge.
      These increases in the cortical MHPG level and NA turnover were significantly
      prevented by co-administration of diazepam (4 mg/kg, i.p.) during chronic
      morphine treatment. These findings suggest that the co-administration of diazepam
      during chronic morphine treatment may prevent some neurochemical changes in the
      central noradrenergic system during chronic morphine treatment, and may suppress
      the development of physical dependence on morphine. Therefore, the inhibitory
      action of GABA via benzodiazepine binding sites may play an important role in the
      development of physical dependence on morphine.

PMID- 8538372
TI  - Modulation of vascular calcium channel activity in response to acute volume
      expansion in rats.
AB  - The mechanisms of the increased resistance in hypertension are still unclear.
      Several studies have indicated that the potential-sensitive Ca2+ channels (PSC)
      are altered in arteries isolated from hypertensive patients or animals. An
      expansion of body fluid volume may trigger local autoregulatory responses or may
      induce the release of humoral factors, either of which could increase systemic
      vascular resistance and cause volume-dependent forms of hypertension. We tested
      the hypothesis that volume expansion per se may cause the alterations of PSC
      similar to those seen in hypertension. For this, we examined the alterations of
      PSC in aortas from volume-expanded rats with the use of dihydropyridine-type Ca2+
      channel activator, BayK 8644, in parallel with the changes in endothelium
      dependent relaxation. Volume expansion was produced by a rapid intravenous
      infusion of saline (10% of body weight) over 30 min in rats. At the end of
      infusion, rats were killed and aorta removed for in vitro measurement of
      isometric tension. Relaxation to acetylcholine (10(-7)-10(-5) mol/L, % relaxation
      to 10(-7) mmol/L norepinephrine contraction) was not significantly changed. In
      contrast, contractile response to BayK 8644 (10(-9)-10(-6) mol/L, % response to
      50 mmol/L KCl) was significantly enhanced in rats with volume expansion (12
      control rats: 11.6 +/- 4.9%; 18 volume-expanded rats: 40.9 +/- 10.4% at 10(-6)
      mol/L, p < 0.05). These findings suggest that acute volume expansion could induce
      a similar enhanced vascular Ca2+ channel activity to that seen in hypertension in
      rats.

PMID- 8538373
TI  - Interaction of ascorbic acid with the neurotoxic effects of NMDA and sodium
      nitroprusside.
AB  - We have previously shown that ascorbic acid (AA) protects cortical neurons in
      culture from the toxic effects of NMDA. In the present study, we examined the
      interactions of AA with toxicity produced by nitric oxide (NO) that is generated
      from the breakdown of sodium nitroprusside (SNP), and with NMDA toxicity measured
      24 h later. AA enhanced SNP toxicity, but it reduced toxicity of NMDA. We propose
      that these data support a model wherein AA produces neuroprotection by an action
      at the NMDA receptor, and indirectly with respect to NO. This effect occurs
      probably by antagonizing Ca2+ influx starting the cascade of biochemical events
      that lead to the production of NO.

PMID- 8538374
TI  - Preparation and characterization of glucosylated aminoglycerophospholipids.
AB  - Natural aminophospholipids were isolated from egg yolk and from human red blood
      cells. Glucosylated ethanolamine and serine phosphatides were prepared by
      exposing synthetic and natural aminophospholipids to glucose for 3-18 h at pH
      7.4. The glucosylation products were resolved from parent phospholipids by normal
      phase high-performance liquid chromatography and were identified by on-line mass
      spectrometry with an electrospray interface. The soft ionization method allowed
      us to detect the glucosylation products as molecular ions of the Schiff bases.
      The Schiff bases could be stabilized by sodium cyanoborohydride reduction. The
      molecular species of the ethanolamine and serine phosphatides reacted in
      proportion to their molar concentration in the mixtures. The yields of the
      glucosylation products varied with time of reaction and the concentration of
      glucose in the medium. At 50 mM glucose and 0.6 mg/mL phosphatidylethanolamine,
      20% of the aminophospholipid was glycated in 18 h at 37 degrees C.

PMID- 8538375
TI  - Structural importance of the cis-5 ethylenic bond in the endogenous desaturation
      product of dietary elaidic acid, cis-5,trans-9 18:2 acid, for the acylation of
      rat mitochondria phosphatidylinositol.
AB  - When rats were fed elaidic (trans-9 18:1) acid at a high load in diets that were
      otherwise marginally or almost completely deficient in linoleic (cis-9,cis-12
      18:2) acid, elaidic acid was desaturated to cis-5,trans-9 18:2 acid. This
      polymethylene-interrupted acid was then incorporated into most phospholipids from
      rat mitochondria, cardiolipin being an exception. Its level of esterification in
      phospholipids followed the increasing order: phosphatidylethanolamine <
      phosphatidylcholine < phosphatidylinositol (PI). The content of cis-5,trans-9
      18:2 acid decreased in organs in the order liver > kidney > heart. The levels of
      cis-5,trans-9 18:2 acid increased in mitochondria phospholipids as the level of
      linoleic acid was lowered in the diet. In liver mitochondria PI, it reached 16%
      of total fatty acids. After hydrolysis of liver mitochondria PI with Naja naja
      phospholipase A2, we observed that elaidic acid was essentially esterified to
      position 1 at the expense of saturated acids, whereas cis-5,trans-9 18:2 acid was
      exclusively esterified to position 2, along with 20:3n-9 and 20:4n-6 acids. As a
      consequence, the sums of saturated and trans-9 18:1 acids on the one hand, and of
      20:3n-9, 20:4n-6, and cis-5,trans-9 18:2 acids on the other hand, remained fairly
      constant in liver mitochondria PI (ca. 55 and 30%, respectively). Because trans-9
      18:1 and cis-5,trans-9 18:2 acids differ only by the cis-5 ethylenic bond, which
      is also present in 20:3n-9 and 20:4n-6 acids, this distribution pattern indicates
      that the cis-5 double bond, rather than any other ethylenic bond, may be of major
      structural importance for channeling fatty acids to position 2 of PI.

PMID- 8538376
TI  - A temperature-sensitive strain of Histoplasma capsulatum has an altered delta 9
      fatty acid desaturase gene.
AB  - We have isolated and characterized the delta 9-desaturase gene (Ole1), which
      codes for a key enzyme involved in regulating membrane fluidity in animal cells
      and microorganisms, from two strains of Histoplasma capsulatum, one that is
      temperature-tolerant (G217B) and the other temperature-susceptible (Downs). These
      pathogenic fungi are dimorphic in that they undergo a morphologic transition from
      the mycelial to yeast-like form when the temperature of incubation is switched
      from 25 to 37 degrees C or when they infect a susceptible host. The coding
      sequences of the two genes, both containing an intron of 93 nucleotides, are
      virtually identical and analogous to the delta 9-desaturase gene of Saccharomyces
      cerevisiae and those of the rat, mouse and human. Ole1 transcription of the
      thermotolerant G217B and thermosensitive Downs strains is similar in yeast phase
      cells and during the temperature shift down from 34, 37, or 40 to 25 degrees C
      (yeast-to-mycelia transition). Nevertheless, the delta 9-desaturase gene is
      transcriptionally inactive in mycelia of G217B at 25 degrees C while it is
      actively transcribed in the Downs strain at the same temperature. These results
      are in agreement with the finding that membranes of the Downs strain have a
      higher level of oleic acid. The differential expression of delta 9-desaturase
      genes is discussed in relationship to differences in thermosensitivity in the
      fungal isolates and in regulating the level of expression of heat shock genes.

PMID- 8538377
TI  - Intestinal and liver fatty acid binding proteins differentially affect fatty acid
      uptake and esterification in L-cells.
AB  - Differential effects of intestinal (I-FABP) or liver (L-FABP) fatty acid binding
      proteins on fatty acid uptake and esterification were examined using transfected
      mouse L-cell fibroblasts. L-FABP, but not I-FABP, expression increased the
      initial rate and extent of cis-parinaric acid uptake by 50 and 29%, respectively,
      compared to control cells. I-FABP and L-FABP expression preferentially increased
      [3H]-oleic acid incorporation into triacylglycerols by 5.5-fold and 3.8-fold,
      respectively. While both L-FABP and I-FABP increased esterification of [3H]-oleic
      acid into ethanolamine glycerophospholipids, these proteins had opposite effect
      on esterification into choline glycerophospholipids. These data show for the
      first time that distinct FABP differentially affect both fatty acid uptake and
      intracellular esterification.

PMID- 8538378
TI  - Effects of bile salts on rat hepatic acyl CoA:cholesterol acyltransferase.
AB  - Acyl CoA:cholesterol acyltransferase (EC2.3.1.26, ACAT), responsible for
      intracellular esterification of cholesterol, may play an important role in
      cholesterol trafficking within the cell, and thus, in maintenance of cellular
      cholesterol homeostasis. Bile acids are potential regulators of cholesterol
      trafficking in the liver. Therefore, the effect of bile salts on hepatic ACAT
      activity was studied in the perfused rat liver. ACAT activity was increased after
      liver perfusion with either taurocholate or taurochenodeoxycholate. However,
      addition of these bile salts at physiological concentrations in vitro had little
      effect on microsomal ACAT activity. The increase in hepatic ACAT activity due to
      perfusion with bile salts was accompanied by reduced accumulation of very low
      density lipoprotein cholesterol in the perfusate, but there was no effect on 3
      hydroxy-3-methylglutaryl-CoA reductase activity. Hepatic ACAT activity was
      decreased after bile diversion for four hours in the intact animal. This
      treatment had no statistically significant effect on 3-hydroxy-3-methylglutaryl
      CoA reductase activity. These data suggest that bile salts induce changes in
      hepatic compartmentation and traffic of cholesterol within the hepatocyte
      accompanied by response of ACAT activity to maintain cellular cholesterol
      homeostasis.

PMID- 8538380
TI  - Proteolytic susceptibility of platelet low density lipoprotein receptor.
AB  - In order to further characterize low density lipoprotein (LDL)-platelet
      interaction, we investigated the effect of protease pretreatment of human
      platelets on the subsequent binding of iodinated LDL (125I-LDL). Our results
      showed that the platelet LDL receptor had a proteolytic susceptibility different
      from that of both classical LDL receptors and the fibrinogen receptor. Platelet
      pretreatment with chymotrypsin, trypsin, and pronase (at 50 micrograms/mL) had no
      effect on 125I-LDL binding, whereas fibroblast 125I-LDL binding was markedly
      reduced. Mild proteolytic digestion, however (up to 1 mg/mL), was helpful in
      characterizing the platelet LDL receptor. Scatchard analysis showed that
      chymotrypsin did not modify LDL binding characteristics, whereas trypsin and
      pronase altered maximal number of binding sites (Bmax) without variation in
      dissociation constant. Trypsin increased Bmax approximately twofold (2156 +/- 327
      binding sites on control platelets vs. 5246 +/- 296 on treated platelets, P <
      0.001, mean +/- SEM, n = 5), but pronase decreased Bmax about 50% (2017 +/- 275
      control vs. 1153 +/- 195 treated, P < 0.001). A minimum of 30 min preincubation
      was required to detect significant effects, and apparent equilibrium was reached
      by 60 min. Maximal increase in platelet LDL binding sites induced by trypsin was
      observed at a protein concentration of 1 mg/mL at 37 degrees C, whereas at 4
      degrees C no effect was found. In contrast, maximal pronase-inhibitory effect
      also was observed at 37 degrees C but at higher protein concentration (10 mg/mL).
      Aprotinin, phenylmethylsulfonylfluoride, and soybean trypsin inhibitor were
      capable of fully blocking both the stimulation and the inhibition of platelet LDL
      binding induced by trypsin and pronase, respectively. Platelet pretreatment with
      both chymotrypsin and pronase (0.5 mg/mL) activated fibrinogen binding sites to a
      similar extent as ADP (100 microM). Furthermore, LDL (at a protein concentration
      of 0.3 mg/mL) increased by 81 +/- 6% the binding of fibrinogen to both protease-
      and ADP-stimulated platelets, but was unable to activate fibrinogen binding sites
      in unstimulated platelets. Overall, the results suggest that platelet LDL
      receptor presents a different proteolytic susceptibility in comparison with both
      "classical" LDL receptor and fibrinogen receptor.

PMID- 8538379
TI  - The effects of simvastatin and cholestyramine, alone and in combination, on
      hepatic cholesterol metabolism in the male rat. off.
AB  - The influence of dietary simvastatin, cholestyramine, and the combination of
      simvastatin plus cholestyramine on hepatic cholesterol metabolism has been
      investigated in male rats. Recovery from the effects of the drugs was also
      investigated by refeeding normal chow for 24 h. Both drugs, alone and in
      combination, increased 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase
      activity in vitro, but activity returned toward control values, after drug
      withdrawal. Acyl-CoA:cholesterol acyltransferase (ACAT) was significantly reduced
      (P < 0.001) by simvastain (-75%), cholestyramine (-71%), and by the drug
      combination (-81%), due both to a decrease in microsomal cholesterol and to
      nonsubstrate-dependent modulation of enzyme activity. Refeeding control diet
      increased ACAT activity but not to control levels. The enhanced activity arose
      partly from higher microsomal cholesterol and partly from increases in total
      enzyme activity. Cytosolic neutral cholesteryl ester hydrolase (CEH) activity was
      substantially elevated by simvastatin (3-fold) and by the drug combination (6
      fold), whereas the effect of cholestyramine was smaller (1.5-fold). Normal chow
      for 24 h only partially returned cytosolic CEH activity to control values.
      Microsomal CEH activity was increased by simvastatin, alone and in combination
      with cholestyramine (1.4 to 1.7-fold), and was also enhanced, in the
      cholestyramine-treated animals, following drug withdrawal. Removal of simvastatin
      did not allow recovery of this enzyme activity, while withdrawal of the drug
      combination led to values 29% below controls. The results indicate that in the
      rat, simvastatin and cholestyramine alter both ACAT and CEH activity, as well as
      inhibiting HMG-CoA reductase activity.

PMID- 8538381
TI  - Effects of randomization of partially hydrogenated corn oil on fatty acid and
      cholesterol absorption, and tissue lipid levels in rats.
AB  - Randomization of partially hydrogenated corn oil containing approximately 45% of
      trans octadecenoic acid only slightly, but not significantly, increased the
      lymphatic fatty acid absorption in rats. No effect of randomization was observed
      on cholesterol absorption. When rats were fed these fats at the 8.8% level (with
      1.2% safflower oil) for three weeks, the concentrations of serum cholesterol, and
      serum and liver phospholipid were significantly higher in randomized fat than in
      control fat, which was composed of 9% high-oleic safflower oil and 1% palm oil.
      Liver cholesterol tended to be higher in randomized fat. In contrast,
      nonrandomized fat was not hyperlipidemic compared to control fat. Although the
      fatty acid composition of liver phospholipids suggested a possible interference
      of trans fatty acid with the metabolism of linoleic acid to arachidonic acid,
      there was no effect of randomization. In the two hydrogenated fat groups, trans
      octadecenoic acid was incorporated and distributed similarly in adipose tissue
      triacylglycerol. These observations indicated that randomization of partially
      hydrogenated fat is not beneficial to various lipid parameters in rats.

PMID- 8538382
TI  - Erythrocyte fatty acids of term infants fed either breast milk, standard formula,
      or formula supplemented with long-chain polyunsaturates.
AB  - The purpose of our study was to assess whether a supplement of fish oil (FO) and
      evening primrose oil (EPO) for formula-fed infants was capable of avoiding
      reductions in erythrocyte docosahexaenoic acid (DHA, 22:6n-3) and arachidonic
      acid (AA, 20:4n-6) associated with standard formula feeding. Healthy, term
      infants, whose mothers chose to formula feed, were randomized to either a placebo
      or supplemented formula for their first 30 wk of life. A reference group of beast
      fed infants also was enrolled. Erythrocyte fatty acids were measured by capillary
      gas chromatography on day 5 and in weeks 6, 16, and 30. Supplementation of
      formula with 0.36% of total fatty acids as DHA resulted in erythrocyte DHA being
      maintained at or above breast-fed levels for the entire 30-wk study period, and
      breast feeding (0.21% DHA) resulted in a modest fall in erythrocyte DHA relative
      to baseline (day 5) values. The level of erythrocyte DHA in placebo formula-fed
      infants was halved by week 16. AA levels decreased in all infants in the first
      six weeks, but the levels in breast- and placebo formula-fed infants increased
      with age and returned to approximate baseline (day 5) values by 16 and 30 wk of
      age, respectively. Erythrocyte AA in FO+EPO-supplemented infants remained low and
      below breast- and placebo formula-fed levels. Our data suggest that dietary
      supplementation with DHA at 0.36% total fatty acids results in erythrocyte DHA
      levels above those found in breast-fed infants. EPO supplementation was not
      effective at maintaining erythrocyte AA when given with FO.

PMID- 8538383
TI  - Differences in fatty acid composition of immature and mature articular cartilage
      in humans and sheep.
AB  - Chondrocytes are imbedded in an avascular, highly charged extracellular matrix
      which could form a barrier to the transfer of dietary essential fatty acids (EFA)
      to chondrocytes. A study was designed to assess the composition of immature and
      mature joint cartilage with respect to essential and nonessential fatty acids
      relevant to EFA deficiency. Cartilage and muscle samples were obtained from human
      fetus, infant and adult cadavers, and from fetal and mature sheep. Lipid extracts
      were prepared and the fatty acid composition determined. In human and sheep joint
      cartilage, linoleic acid (LA; 18:2n-6) content was lower, and n-9 eicosatrienoic
      acid (ETrA; 20:3n-9) and arachidonic acid (AA; 20:4n-6) were higher in fetuses
      compared to mature subjects. An intermediate pattern was seen in infant
      cartilage. n-3 Fatty acids tended to be higher in fetal than in mature cartilage
      in humans and in sheep. In human muscle (and in other noncartilaginous comparison
      tissues), similar differences between fetuses and adults were seen in LA and AA,
      but not in ETrA. In fetal sheep muscle, very low LA, reduced AA and raised ETrA
      levels compared to mature sheep muscle were seen. However, although the pattern
      is characteristic of EFA deficiency, the abundance of n-6 EFA in liver and spleen
      of human fetuses and of n-3 EFA in liver and spleen of fetal sheep suggests that
      placental transfer of EFA is not likely to be limiting. During fetal development,
      the metabolism of fatty acids is distinctive and differs between the species.
      ETrA appears to be a readily measurable component of some tissues at certain
      stages of development when its presence in tissues does not indicate EFA
      deficiency.

PMID- 8538384
TI  - Dietary fish oil and cytochrome P-450 monooxygenase activity in rat liver and
      kidney.
AB  - Lauric acid hydroxylation and aminopyrine N-demethylation were studied in kidney
      and liver microsomes from rats treated with fish oil. Different doses of fish oil
      containing 20% eicosapentaenoic acid and 10% docosahexaenoic acid were provided
      daily to the rats for seven days. In all the groups studied, the lauric acid
      metabolism was higher in kidney microsomes and the aminopyrine metabolism in the
      liver microsomes. Although no effect on the renal cytochrome P-450 concentration
      was detectable, all four fish oil doses increased the hepatic concentration of
      cytochrome P-450 by a mean 27%. The higher fish oil doses used increased the
      renal and hepatic microsomal metabolism of aminopyrine. The lauric acid
      metabolism was increased by fish oil only in the liver. Fish oil, a known inducer
      of fatty acid peroxisomal beta-oxidation, also induced microsomal activity. These
      results show that liver and kidney respond in different ways to dietary factors
      such as fish oil. In addition, our study would suggest that fish oil increased
      the activity of two different families of liver cytochrome P-450. The activity of
      kidney lauric acid 11- and 12-hydroxylation, however, was not modulated by fish
      oil.

PMID- 8538386
TI  - Increased formation and degradation of malondialdehyde-modified proteins under
      conditions of peroxidative stress.
AB  - The effect of increased in vivo lipid peroxidation on excretion of the main
      urinary metabolites of malondialdehyde (MDA) was investigated. peroxidative
      stress in the form of vitamin E deficiency or the administration of iron
      nitrilotriacetate or carbon tetrachloride was imposed on rats fed an MDA-free
      diet. Significant increases were observed in excretion of the lysine-MDA adduct
      epsilon-propenal lysine, its N-acetyl ester, and free MDA. Under the conditions
      imposed, the increments in excretion of the lysine adducts reflect increased
      peroxidative modification of tissue proteins in vivo. These adducts also were
      found to be the main forms of MDA excreted in human urine. Reacting 14C-bovine
      serum albumin (BSA) with MDA resulted in its accelerated proteolysis in vitro by
      soluble enzyme preparations derived from human erythrocytes and rat liver
      mitochondria. The increments observed were similar to those reported for the
      hydrolysis of BSA following its exposure to hydroxyl radicals. The results show
      that lipid peroxidation in vivo results in peroxidative damage to tissue proteins
      and indicate that such proteins are subject to an accelerated rate of
      proteolysis.

PMID- 8538385
TI  - Effects of peroxidative stress and age on the concentration of a deoxyguanosine
      malondialdehyde adduct in rat DNA.
AB  - The effect of age and peroxidative stress on the concentration of a
      deoxyguanosine malondialdehyde adduct (dG-MDA) in rat tissues was investigated.
      Vitamin E deficiency had no effect on the dG-MDA content of liver DNA in rats fed
      a diet containing 10% corn oil. When 2% cod liver oil was added to this diet, the
      dG-MDA content of liver DNA doubled in the positive controls fed a high level of
      vitamin E (100 ppm dl-alpha-tocopherol), and there was a further increase when
      vitamin E was deleted. Neither iron nitrilotriacetate administration nor choline
      deficiency had any effect on the dG-MDA content of liver DNA. Carbon
      tetrachloride had a lowering effect. The failure of iron or carbon tetrachloride
      administration and of vitamin E deficiency to increase liver dG-MDA is consistent
      with their failure in previous experiments to affect the urinary excretion of dG
      MDA. In contrast, these forms of peroxidative stress produce large increments in
      the urinary excretion of MDA adducts with lysine, reflecting increased formation
      and degradation of MDA-modified proteins. DNA appears to be protected from
      modification by MDA produced at extranuclear sites. The frequency of dG-MDA in
      different tissues of 4-month-old rats varied markedly: brain >> liver > kidneys
      and testes. Higher concentrations of dG-MDA were found in the liver and kidneys,
      but not the testes, of 25-month-old rats. The determinants of the concentration
      of dG-MDA in DNA merit further investigation.

PMID- 8538387
TI  - Maryland physicians during World War II: a portrait. Introduction.

PMID- 8538388
TI  - Preparing for a real war.

PMID- 8538389
TI  - Col. Thomas B. Turner, M.C.

PMID- 8538390
TI  - Casualties from the war.

PMID- 8538391
TI  - Army service, 1942-1946.

PMID- 8538393
TI  - In the Trinidad sector.

PMID- 8538392
TI  - To grow strong.

PMID- 8538394
TI  - Lt. Col. Theodore E. Woodward, M.C.

PMID- 8538395
TI  - The 18th General Hospital.

PMID- 8538396
TI  - Colonel Benjamin M. Baker, M.C.

PMID- 8538397
TI  - Lt Everard F. Cox.

PMID- 8538399
TI  - The 42nd General Hospital.

PMID- 8538398
TI  - Pacific memories.

PMID- 8538400
TI  - Reminiscences of the 42nd General Hospital during World War II.

PMID- 8538401
TI  - Nurses of the 42nd.

PMID- 8538402
TI  - Observations of a medical consultant.

PMID- 8538403
TI  - The 142nd General Hospital.

PMID- 8538404
TI  - The 118th General Hospital.

PMID- 8538405
TI  - Maj. William E. Grose, M.C.

PMID- 8538406
TI  - A view from Australia.

PMID- 8538407
TI  - Lessons of the Pacific fighting.

PMID- 8538408
TI  - Battalion surgeon in the South Pacific.

PMID- 8538409
TI  - Maj. Eli M. Lippman, M.C.

PMID- 8538410
TI  - On Okinawa.

PMID- 8538411
TI  - Memories of wartime.

PMID- 8538412
TI  - Capt. H. Leonard Warres, M.C.

PMID- 8538413
TI  - From Naples to the Brenner Pass.

PMID- 8538414
TI  - Lt. Col. Theodore E. Woodward, M.C.

PMID- 8538415
TI  - In Burma with Merrill's Marauders.

PMID- 8538416
TI  - Capt. James E.T. Hopkins, M.C.

PMID- 8538417
TI  - June 6, 1944.

PMID- 8538418
TI  - Prisoner of war.

PMID- 8538419
TI  - Lt. Marvin J. Rombro.

PMID- 8538420
TI  - An itinerant medical-military odyssey.

PMID- 8538421
TI  - The 56th General Hospital.

PMID- 8538422
TI  - With the 123rd Evacuation Hospital in France and Germany.

PMID- 8538423
TI  - Witness to the liberation.

PMID- 8538424
TI  - In Korea, then home.

PMID- 8538425
TI  - Operation crossroads.

PMID- 8538426
TI  - Histopathology of muscle flap microcirculation following prolonged ischemia.
AB  - The purpose of this study was to evaluate histological changes occurring in the
      microcirculation of a muscle flap following prolonged ischemia and to correlate
      them with the flow hemodynamics. The cremaster muscle flap model was used for
      direct in vivo studies of the microcirculation. In 45 rats, vascular clamps were
      applied to the iliac and femoral vessels following flap isolation. Flaps were
      subjected to various periods of ischemia, ranging from 4 to 6 hours, and 2 hr of
      reperfusion. In vivo observations of the microcirculation and vessel diameter
      measurements were taken at 1 hour intervals for an 8 hr period. With prolonged
      ischemia, return of circulation to the flap was delayed and no flow was observed
      following 6 hr of ischemia. Morphologic changes at 6 hr revealed red cell and
      platelet thrombi formation within the capillaries, marked dilatation of
      postcapillary venules, endothelial swelling in the capillaries, and
      microhemorrhage formation around the venules.

PMID- 8538427
TI  - Effect of postischemic reperfusion on microcirculation and lipid metabolism of
      skeletal muscle.
AB  - To study the effect of ischemia reperfusion injury on microvascular reactivity
      and tissue metabolism in skeletal muscle, a Sprague-Dawley rat cremaster muscle
      was prepared as a tourniquet ischemia model and subjected to 2 hr ischemia
      followed by 1 hr reperfusion to simulate the timing of ischemia during
      microvascular surgery. The dose-response curve of arteriolar reactivity to
      norepinephrine, lipid peroxidation, and ultrastructure of capillaries was
      determined in both the control and postischemic reperfusion stages. Judging from
      the results, we summarize our observations as follows: (1) Postischemic
      reperfusion significantly increased arteriolar reactivity to norepinephrine, in
      which the EC50 for vasoconstriction decreased in all three orders of arterioles.
      These results suggest that reperfusion could have impaired the vasodilation
      control mechanism, possibly being endothelium dependent. (2) Lipid peroxidation
      increased sixfold in the reperfusion group, suggesting that oxygen free radicals
      have produced significant tissue damage under the created conditions. (3)
      Significant endothelial damage in the capillaries shown by electron microscope
      observation supports these studies, indicating that ischemia/reperfusion in
      clinically transplanted skeletal muscles could cause significant damage to the
      tissue microcirculation both physiologically and metabolically.

PMID- 8538428
TI  - Microvenous thrombosis rates following anastomosis with vein grafting and a
      knotted suture.
AB  - An experimental microvenous thrombosis model was developed combining vein
      grafting in femoral vein defects with exaggerated vessel injuries using a knotted
      suture in the vessel repair. The rat femoral vein grafts were separately
      subjected to injuries caused by an anastomosis performed with a suture knotted
      with eight half-hitches at the distal anastomosis (upstream), the proximal
      anastomosis (downstream), and both anastomotic sites. These groups were compared
      to vein grafting done with a standard suture. Vessel patency was assessed at 20
      min and 24 hr, and the thrombus component was histologically analyzed at 24 hr
      after the procedures. One hundred percent of control vein grafts were patent at
      24 hr. All experimental groups had significantly decreased patency at 24 hr (P <
      0.001). Among the experimental groups, knotted suture anastomoses at both
      anastomoses produced significantly lower patency (13.3%, P < 0.05) than knotted
      suture anastomoses at distal anastomoses. Histological analyses of thrombosed
      grafts showed that a large amount of thrombocyte deposition and inflammatory
      cells were noted at both anastomotic sites in the vein grafts with a knotted
      suture at the distal anastomosis and in the grafts with a knotted suture at both
      anastomoses. Thrombocyte deposition and inflammatory cells were seen only at the
      site of proximal anastomosis when using a knotted suture at the proximal
      anastomosis site alone. This study demonstrated that quantified microvenous
      thrombosis can be produced by exaggerating vessel injuries with a knotted suture
      in a vein graft model. This thrombosis model can be used to study the effects of
      antithrombogenic agents.

PMID- 8538429
TI  - Comparison of nylon and polypropylene sutures in a microvenous thrombosis model.
AB  - Thrombosis rates of femoral end-to-end microvenous anastomoses with nylon and
      polypropylene sutures (9-0 suture, 70 mu needle) were compared in a microvenous
      thrombosis model. The vessel injuries were produced during anastomosis by using a
      suture with a knot 1 cm from the needle. Anastomotic thrombosis rates were
      assessed by visual inspection and strip test at 24 hr postoperatively. Low
      thrombosis rates (0% and 20%, respectively) of anastomoses with both unknotted
      nylon and unknotted polypropylene sutures were obtained. Anastomoses with knotted
      nylon and polypropylene sutures resulted in 65% and 45% thrombosis rates,
      respectively. Statistical analyses showed that there were no significant
      differences between thrombosis rates, both in anastomosis performance with
      unknotted nylon and polypropylene sutures (P > 0.05) and with knotted nylon and
      polypropylene sutures (P > 0.05), while there were significant differences
      between the thrombosis rate using unknotted sutures and knotted sutures (P <
      0.01). It was concluded that vascular injury, not suture material, is the main
      factor leading to thrombosis in this model.

PMID- 8538430
TI  - Modified crush-avulsion anastomosis model on the rat femoral vein.
AB  - A crush-avulsion anastomosis model was established on the rat femoral vein.
      Saline or heparin was used as a luminal topical agent and was allowed to contact
      the damaged endothelium for 10 min. Patency and coagulation parameters were
      investigated for 1 week. The heparin treated group had a patency rate of 93% at 1
      hr vs. 13% for the saline treated group (P < 0.001). At 7 days, the heparin
      treated group had an 87% patency vs. 7% for the saline-treated group (P < 0.001).
      Scanning electron micrography (SEM) provided evidence of the deposition of the
      components of early thrombosis in the crushed venous wall. In contrast, the SEM
      of the heparin treated group shows a paucity of any evidence of thrombus. These
      results indicate that the rat vein crush-avulsion model is a reliable and
      reproducible thrombosis model with low patency. The methods used with the topical
      agent may improve the patency rate in crush avulsion injuries.

PMID- 8538431
TI  - Topical GM1 ganglioside to promote crushed rat sciatic nerve regeneration.
AB  - The effects of topical GM1 ganglioside on crushed rat sciatic nerve regeneration
      were studied in this presentation. Thirty-four rats, with 68 bilateral sciatic
      nerves, were divided into seven groups: one group of four rats for measurement of
      normal motor nerve conduction velocity (MNCV), three as controls, and another
      three in the GM1-treated groups. Sciatic nerves were exposed and crushed at a
      site 6 mm distal to the sciatic notch by the standard technique. In this manner,
      3 mm wide crush injuries were created. Then 2.1 microliters of normal saline was
      injected into the crush site in the control groups and an equal volume of GM1
      solution (containing 10 micrograms GM1) was injected into the GM1-treated groups.
      Electrophysiological, histological, and morphometric evaluations were carried out
      at 12, 28, and 56 days. A significantly higher muscle action potential (MAP) rate
      was found in the GM1-treated group (70%) vs. the controls (none) at 12 days (P <
      0.005), and increased MNCV was found in the GM1-treated groups at both 28 and 56
      days, especially at 56 days, when it was 39.59 +/- 9.23 m/sec vs. 31.42 +/- 4.07
      m/sec in controls (P < 0.05). Morphometrically, there were more regenerated
      myelinated fibers (RMFs) at 12 days, and larger diameter of RMFs were observed at
      12, 28, and 56 days in the GM1-treated groups.

PMID- 8538432
TI  - Effects of nerve growth factor on crushed sciatic nerve regeneration in rats.
AB  - The effects of nerve growth factor (NGF) on crushed sciatic nerve regeneration
      were studied in 30 rats, with 60 bilateral nerves. The nerves were crushed at a
      site 6 mm distal to the sciatic notch by the standard technique and 3 mm wide
      crush injuries were created. Then 2.1 microliters of normal saline in the control
      groups and an equal volume of NGF solution (containing 1 microgram of NGF) in the
      NGF-treated groups was injected into the crush sites and followed for 12, 28, and
      56 days, respectively. At the end of the observation, electrophysiological
      evaluation was carried out; then samples 10 mm distal to the crush site were
      removed and prepared for histological and morphometric studies. Evoked muscle
      action potential (MAP) was recorded in 50% of the NGF-treated group at 12 days
      but not in the control group; the difference was statistically significant (P <
      0.05). The motor nerve conduction velocity (MNCV) was increased in NGF-treated
      groups compared with control groups at 28 and 56 days (P < 0.05).
      Morphometrically, significantly more regenerated myelinated fibers (RMFs) were
      seen at 12 days, and larger diameter RMFs were found at 12, 28, and 56 days in
      NGF-treated groups than in control groups. These results indicate that topically
      applied NGF stimulates nerve regeneration and promotes function recovery in
      crushed rat sciatic nerves.

PMID- 8538433
TI  - Application of sciatic functional index in nerve functional assessment.
AB  - In order to confirm the reliability of the sciatic functional index (SFI) in the
      rat, SFI, muscle strength, electrophysiological, and morphometric assessments
      were carried out from the 10th day to the sixth month after nerve injury or
      repair. The results showed that the SFI has a positive correlation with all
      tested indices of muscle strength, electrophysiology, and morphology (r = 0.925
      0.996, P < 0.01 or P < 0.001). These results indicate that the SFI is a reliable
      index for evaluating rat sciatic nerve regeneration and can be widely used.

PMID- 8538434
TI  - Patterns of thermoregulation associated with cold intolerance after digital
      replantation.
AB  - Twelve patients with complete thumb amputations were analyzed to determine the
      interrelations between thermoregulation for pain and cold intolerance and sensory
      nerve recovery. Patients were examined at 3 months, 6 months, 1 year, and after 2
      years following replantation. Medical thermography was introduced to assess
      postoperative circulation following digital replantation, while vasomotor tone
      was assessed by cold-stress plethysmography testing. Postoperative circulation
      was divided into two different patterns based upon skin temperature, the
      transition of which over time correlated well with sensory nerve recovery.
      Patients with cold intolerance showed a persistent vasoconstriction pattern, the
      cold change of which was objectively detected by thermography.

PMID- 8538435
TI  - Aneurysms of the digital artery: a review and report of three cases.
AB  - Aneurysms of the digital artery are rare. Since 1980, we have treated three
      traumatic aneurysms of the digital artery. There were two lesions of the common
      palmar digital artery and one of the ulnar pollicis artery. One case was caused
      by a traumatic laceration with a kitchen knife, and two cases were caused by
      repetitive microtrauma. On histologic examination, there were two true aneurysms
      and one false aneurysm. Two cases were treated by excision only, and one case was
      treated by excision and reanastomosis. The operating microscope was useful during
      neurolysis, excision of the aneurysm, and vascular anastomosis.

PMID- 8538436
TI  - Intercostal nerve crossing to restore elbow flexion and sensibility of the hand
      for a root avulsion type of brachial plexus injury.
AB  - Ten patients with a root avulsion type of brachial plexus injury were treated
      with simultaneous intercostal nerve crossing to the musculocutaneous and median
      nerves, and nine cases were followed for more than 40 months. The average
      interval from injury to surgery was 2.7 months. The average age at operation was
      18.6 years. The elbow flexor was M4 in six patients, M3 in two patients, and M1
      in one patient. The wrist flexor was more than M3 in six patients and less than
      M2 in four patients. The finger flexor was more than M3 in four patients and less
      than M2 in five patients. Protective sensation in the areas innervated by the
      musculocutaneous and median nerves was restored in all cases.

PMID- 8538437
TI  - Evaluation of the effectiveness of sensory reeducation following digital
      replantation and revascularization.
AB  - Sensory recovery following digital replantation plays an important role in the
      restoration of hand function. Twelve patients with twenty-four replanted or
      revascularized digits were randomly selected to enter a program of sensory
      reeducation, and another 15 patients with 22 replanted or revascularized digits
      were selected as controls who did not receive sensory reeducation. A moving two
      point discrimination and a Semmes-Weinstein pressure threshold test were
      evaluated for monitoring the sensory recovery. The period of sensory reeducation
      was 18.83 weeks on average, and the mean follow-up time was 11.94 months. The
      group that received sensory reeducation significantly improved to a better degree
      of moving two-point discrimination and Semmes-Weinstein threshold level by both
      univariate and multiple regression analysis. We suggest that sensory reeducation
      should be an integral part of the postoperative rehabilitation protocol following
      digital replantation and revascularization.

PMID- 8538438
TI  - Delayed sensory reeducation after toe-to-hand transfer.
AB  - The effect of a delayed program of sensory rehabilitation was evaluated in 13
      patients with a total of 22 toe-to-hand transfers. Each patient was begun on a
      protocol of sensory reeducation at a mean of 38 months (range 13-98 months) after
      the transfer. Home rehabilitation, employing a Disk-Criminator (TM) program, was
      monitored at monthly intervals by the therapist for a mean of 3.3 months, at
      which time a final evaluation of sensibility was done. Each of the 22 toe
      transfers improved by an average of 7 mm in static and 6 mm in moving two-point
      discrimination. The improvement in two-point discrimination following delayed
      implementation of sensory reeducation was statistically significant at the P <
      0.0001 level.

PMID- 8538439
TI  - Two immediate synchronous free flap transfers in a severe traumatic mid-hand
      defect: a case report.
AB  - A 66-year-old patient sustained a severe right hand injury resulting in a thumb
      pulp defect and unreplantable amputation of the index, long, and ring fingers at
      the metacarpophalangeal joint with joint exposure. There was also an 8 cm defect
      of the radial digital nerve of the little finger. Immediate one-stage total
      reconstruction of all of the defects was accomplished by a free groin flap and a
      free glabrous skin flap from the foot. Opposable function of the hand was thus
      preserved.

PMID- 8538440
TI  - The role of instance retrieval in understanding complex concepts.
AB  - Conceptual combination studies have found that a property is often judged more
      salient in a complex concept than in its constituents. Medin and Shoben (1988),
      for example, found that metal is more typical than wooden of the simple concept
      SPOON, whereas wooden is more typical than metal of the complex concept LARGE
      SPOON. We explored the possibility that such typicality reversals reflect a
      process of instance retrieval; that is, subjects base their typicality judgments
      on previously stored instances of LARGE SPOON. This hypothesis predicts that
      performance in a task requiring typicality judgments and one requiring instance
      retrieval would be correlated. Three experiments supported this prediction.
      Experiment 1 provided typicality reversals for a set of concepts. Subjects in
      Experiments 2 and 3 described instances of the concepts. Aspects of these
      descriptions were used to predict the reversals. The correlation between
      predicted and obtained typicality reversals was substantial, and higher for
      concepts for which subjects retrieved many instances.

PMID- 8538441
TI  - The effects of interaction with the device described by procedural text on
      recall, true/false, and task performance.
AB  - In two experiments, subjects interacted to different extents with relevant
      devices while reading two complex multistep procedural texts and were then tested
      with task performance time, true/false, and recall measures. While reading,
      subjects performed the task (read and do), saw the experimenter perform the task
      (read and see experimenter do), imagined doing the task (read and imagine),
      looked at the device while reading (read and see), or only read (read only). Van
      Dijk and Kintsch's (1983) text representation theory led to the prediction that
      exposure to the task device (in the read-and-do, read-and-see, and read-and-see
      experimenter-do conditions) would lead to the development of a stronger situation
      model and therefore faster task performance, whereas the read-only and read-and
      see conditions would lead to a better textbase, and therefore better performance
      on the true/false and recall tasks. Paivio's (1991) dual coding theory led to the
      opposite prediction for recall. The results supported the text representation
      theory with task performance and recall. The read-and-see condition produced
      consistently good performance on the true/false measure. Amount of text study
      time contributed to recall performance. These findings support the notion that
      information available while reading leads to differential development of
      representations in memory, which, in turn, causes differences in performance on
      various measures.

PMID- 8538442
TI  - Why is 9 + 7 harder than 2 + 3? Strength and interference as explanations of the
      problem-size effect.
AB  - In four experiments, the problem-size effect was investigated, using an alphabet
      arithmetic task in which subjects verified such problems as A + 2 = C. Problem
      size was manipulated by varying the magnitude of the digit addend (e.g., A + 2, A
      + 3, and A + 4). The frequency and similarity of problems was also manipulated to
      determine the contribution of strength and interference, respectively. Experiment
      1 manipulated frequency at low levels of practice and found that strength could
      account for the problem-size effect. Experiment 2 manipulated frequency at higher
      levels of practice, and found that strength alone could not account for the
      problem-size effect at asymptote. Experiment 3 manipulated frequency and
      similarity and found a substantial problem-size effect at asymptote, suggesting
      that both strength and interference contribute to the problem-size effect.
      Experiment 4 manipulated similarity, keeping frequency constant, and found no
      problem-size effect at asymptote, suggesting that interference alone is not
      responsible for the problem-size effect. The results are related to findings with
      number arithmetic.

PMID- 8538443
TI  - Item-specific interference caused by cue-dependent forgetting.
AB  - Memory for A-B word pairs (e.g., child-apple) was tested by a cued recall test
      (e.g., child-app__). Showing an A-C "relative" (e.g., child-bicycle) reduced
      recall, especially if it was shown recently and was highly accessible
      (Experiments 1 and 2). In Experiment 3, a relative facilitated recall if it was
      semantically similar to the target (A-B': child-cookies) but interfered if it was
      semantically dissimilar (A-C: child-fever). The best explanation for these
      results is that the relative primed features that affected the functional
      retrieval cue, and that interference occurred if the cue did not match the trace
      for the target (Martin, 1972). In other words, the interference effects are an
      example of cue-dependent forgetting. Neither blocking nor a discrimination
      process can account for these findings, although some evidence for a
      discrimination process has been found with other materials.

PMID- 8538444
TI  - Reasoning about the referent of a picture versus reasoning about the picture as
      the referent: an effect of visual realism.
AB  - Research on picture perception and picture-based problem solving has generally
      considered the information that enables one to "see" and think about a picture's
      subject matter. However, people often reason about a picture or representation as
      the referent itself. The question addressed here is whether pictorial features
      themselves help determine when one reasons about the referent of an image, as
      with an engrossing movie, and when one reasons about the image in its own right,
      as with abstract art. Two experiments tested the hypothesis that pictures with
      relatively high fidelity to their referents lead people to think about those
      referents, whereas pictures with relatively low fidelity lead people to think
      about the picture as a referent. Subjects determined whether marks on the bottom
      and top boards of an open hinge would meet if the hinge were closed. Accuracy and
      latency results indicated that subjects who saw realistic displays simulated the
      physical behavior of the hinge through analog imagery. In contrast, subjects who
      saw schematic displays tended to reason about static features of the display such
      as line lengths and angles. The results demonstrate that researchers must be
      cautious when generalizing from reasoning about diagrammatic materials to
      reasoning about the referents themselves.

PMID- 8538445
TI  - Effects of learning contexts on implicit and explicit learning.
AB  - Two parallel tasks involving rule learning were identified in Experiment 1A and
      were used to assess implicit and explicit learning. In both tasks, subjects had
      to input numbers in order to reach the target values of outputs. The relationship
      between inputs and outputs was either simple (in the simple task) or complex (in
      the complex task), and the way in which target values were presented could be in
      the form of either numbers (in the simple task) or lines (in the complex task).
      Experiment 1B examined the validity of the explicit measure in the complex task.
      Experiments 2-4 investigated the interaction between learning contexts and the
      simple/complex learning tasks. Verbalization and instructions to search for the
      rules facilitated the simple-task learning and hurt or have no effect on the
      complex-task learning. In the observational-learning condition, no learning
      occurred for the simple task, and the complex task learning was impaired. These
      results suggest that the complex task and simple task involve two distinct
      learning systems. Other implications are also discussed.

PMID- 8538446
TI  - Individual differences in working memory strategies for reading expository text.
AB  - This study investigated whether individual differences in working memory (WM)
      span are associated with different WM management strategies during the reading of
      expository text. In Experiment 1, probe questions were presented on line during
      reading to determine whether thematic information was maintained in WM throughout
      comprehension. The data indicated that readers across the range of WM span
      maintained thematic information in WM throughout the reading of a given passage.
      In Experiment 2, sentence reading times and accuracy for both topic and detail
      questions were measured in two conditions: when topic sentences were present and
      when topic sentences were absent. Subjects performed similarly across the range
      of WM span in the topic-present condition, but lower span subjects performed more
      poorly on detail questions in the topic-absent condition. In Experiment 3, the
      topic-present condition of the second experiment was replicated, except that
      subjects expected to receive questions about details only. Thematic processing
      and retention of topic and detail information all increased with span. Taken
      together, these results suggest that, for more difficult text processing tasks,
      high- and low-span subjects adopt different WM management strategies and these
      strategies influence what is learned from reading the text.

PMID- 8538447
TI  - The functions of phonology in the acquisition of reading: lexical and sentence
      processing.
AB  - It has been claimed (V. Coltheart, Laxon, Rickard, & Elton, 1988) that learners
      as well as skilled readers use phonology for multiple functions in reading-for
      meaning tasks. This claim was examined using lexical decision and sentence
      evaluation tasks. It was found in the first experiment that the type of
      instruction learners had received determined whether there was prelexical use of
      phonology in responding to items out of sentence context. Type of instruction had
      no effect when the items were in context. In the second experiment, performances
      on a homophone sentence evaluation task and a homophone semantic decision task,
      which excluded sentence processing, were examined. The results suggest that
      phonology served the function of access to lexical meanings in addition to any
      function in postlexical sentence processing. The obtained relationships between
      relative frequencies of the presented and unpresented homophone mates and item
      accuracy on these tasks were inconsistent with exclusive use of "direct access"
      but consistent with access of lexical meaning via phonology and application of a
      "spelling-check" procedure when multiple homophonic meanings are activated.

PMID- 8538448
TI  - Is writing as difficult as it seems?
AB  - Experiment 1 assessed the time and effort allocated to writing subprocesses while
      generating written and verbal protocols over 10 weekly writing sessions. Within a
      40-min session, planning time consumed about 45% in the first 5 min, but
      stabilized at near 30% thereafter. Generating text initially consumed 40% of the
      writers' time, peaked at 50% midway, and then declined to its original level. The
      time spent revising and reviewing was negligible early in writing sessions, but
      increased substantially late in the sessions. The highest and lowest quality
      documents could be differentiated on the basis of the amount of time the writers
      devoted to revising and to the magnitude of their RTs in a secondary interference
      task. Writers showed consistent, distinctive patterns of transitional
      probabilities between writing subprocesses both within and across sessions,
      yielding quantitative representations of their writing styles. In Experiment 2,
      writers overestimated the amount of time they devote to revising and
      overestimated the amount of effort they allocate to planning and text generation.
      Their estimations did not improve after 10 weeks of composing. A time-and-effort
      based analysis of writing is proposed to account for these data.

PMID- 8538449
TI  - Reconstructive memory in the dating of personal and public news events.
AB  - Two experiments investigated memory for the dates of events selected and recorded
      by subjects in diaries. In Experiment 1, personal events and public news events
      were compared, with retention time varying from 1 week up to 9 months. It was
      found that the day of the week was more accurately identified for personal events
      than for news events, that day-of-the-week (DOW) accuracy did not decrease with
      increasing retention time, and that memory of the personal context of both event
      types was more important for DOW accuracy than was memory of the core of the
      events. These results support our view that memory of the day of the week is
      mainly reconstructed by reference to a temporal week schema based on personal
      experiences, and that the relation of news events to the week schema is mediated
      by memory of personal context. The distribution of DOW errors was modeled as the
      outcome of a process of guessing constrained by subdivisions of the week schema,
      without assuming any special temporal memory trace. In Experiment 2, the model
      was shown to fit independently collected data from a different subject pool and
      country equally well.

PMID- 8538450
TI  - Linkage at steady state: allosteric transitions of thrombin.

PMID- 8538451
TI  - Thermal denaturation methods in the study of protein folding.

PMID- 8538453
TI  - Tight binding affinities determined from thermodynamic linkage to protons by
      titration calorimetry.
AB  - A general titration calorimetry method is described that can be used to determine
      the affinity of tight binding interactions with proteins. The method is based on
      the thermodynamic linkage between ligand binding and coupled protonation
      reactions. The protons linked to a given ligand-binding reaction are measured by
      titration calorimetry, and integration of the resulting data set yields the pH
      dependence of the binding affinity based on thermodynamic relationships developed
      elsewhere. When the pH dependence of the binding affinity is combined with the
      absolute affinity determined independently at a pH at which the affinity can be
      conveniently measured, the absolute binding affinity over the entire pH range is
      determined. The method is well suited for determining high-affinity binding
      interactions of protein antigens with antibodies, but is applicable to any
      macromolecular ligand-binding reaction that is coupled to protonation.

PMID- 8538452
TI  - Kinetics of lipid membrane phase transitions: a volume perturbation calorimeter
      study.

PMID- 8538454
TI  - Probes of energy transduction in enzyme catalysis.

PMID- 8538455
TI  - Calorimetric methods for interpreting protein-ligand interactions.

PMID- 8538456
TI  - Extracting thermodynamic data from equilibrium melting curves for oligonucleotide
      order-disorder transitions.

PMID- 8538457
TI  - Predicting thermodynamic properties of RNA.

PMID- 8538458
TI  - Thermodynamics and mutations in RNA-protein interactions.

PMID- 8538459
TI  - Melting studies of RNA unfolding and RNA-ligand interactions.

PMID- 8538460
TI  - Structural-perturbation approaches to thermodynamics of site-specific protein-DNA
      interactions.

PMID- 8538461
TI  - Thermodynamic parameters from hydrogen exchange measurements.
AB  - Just as exchangeable hydrogens that are controlled by global unfolding can be
      used to measure thermodynamic parameters at a global level, hydrogens that are
      exposed to exchange by local unfolding reactions may be used to obtain locally
      resolved energy parameters. Results with the hemoglobin system demonstrate the
      ability of HX methods to locate functionally important changes in a protein and
      to measure the energetic contribution of each. These results offer the promise
      that HX measurements may be used to delineate, in terms of definable bonds and
      their energies and interactions, the network of interactions that Hb and other
      proteins use to produce their various functions.

PMID- 8538462
TI  - Application of pressure to biochemical equilibria: the other thermodynamic
      variable.

PMID- 8538463
TI  - Molecular volume.

PMID- 8538464
TI  - Hydrostatic and osmotic pressure as tools to study macromolecular recognition.
AB  - Clearly, hydrostatic and osmotic pressure techniques offer unique potential in
      the study of fundamental problems of molecular recognition in biological systems.
      With the recent advances in technology such investigations are rapidly becoming
      commonplace. We look forward to further advances and their report in succeeding
      compendiums such as this volume.

PMID- 8538465
TI  - Sedimentation equilibrium as thermodynamic tool.

PMID- 8538466
TI  - Macromolecules and water: probing with osmotic stress.

PMID- 8538467
TI  - Footprint phenotypes: structural models of DNA-binding proteins from chemical
      modification analysis of DNA.

PMID- 8538468
TI  - Low-temperature electrophoresis methods.

PMID- 8538469
TI  - Use of multiple spectroscopic methods to monitor equilibrium unfolding of
      proteins.

PMID- 8538470
TI  - Probing structural and physical basis of protein energetics linked to protons and
      salt.

PMID- 8538471
TI  - Evaluating contribution of hydrogen bonding and hydrophobic bonding to protein
      folding.

PMID- 8538472
TI  - Analyzing solvent reorganization and hydrophobicity.

PMID- 8538473
TI  - Simple force field for study of peptide and protein conformational properties.

PMID- 8538474
TI  - Probes for analysis of stability of different variants of aspartate
      aminotransferase.

PMID- 8538475
TI  - Thermodynamic approaches to understanding aspartate transcarbamylase.

PMID- 8538476
TI  - On the interpretation of data from isothermal processes.

PMID- 8538477
TI  - Linkage of protein assembly to protein-DNA binding.

PMID- 8538478
TI  - Efficacy and tolerance of Menorest compared to Premarin in the treatment of
      postmenopausal women. A randomised, multicentre, double-blind, double-dummy
      study.
AB  - Two-hundred and fourteen (214) menopausal women with moderate to severe vasomotor
      symptoms, aged 40-65 years, were randomised. After a 4-week treatment-free
      period, each women received a continuous regimen of Menorest 50 twice weekly or
      Premarin 0.625 mg daily, for 12 weeks. Didrogesterone 10 mg was also given to all
      women for 12 days of every 28-day cycle. The objectives were to compare the
      efficacy and safety profiles of Menorest and an oral estrogen. A statistically
      significant reduction in the mean number of hot flushes occurred in each group
      compared to baseline with a decrease from 7.1 at baseline to 0.9 at 12 weeks in
      the Menorest group, and from 6.7 to 0.5 in the oral estrogen group; there was no
      statistically significant difference between the two groups (P = 0.36). With each
      successive treatment cycle, there was a continuous improvement in the number of
      hot flushes. The incidence and severity of menopausal symptoms were reduced in
      the same manner in both groups. There were no statistically significant
      differences in the mean plasma estradiol and estrone concentrations between the
      two treatment groups after 10 weeks of therapy. The mean estradiol to estrone
      ratio was similar in both groups, as was the number of adverse events observed.
      In summary, Menorest was as effective as an oral estrogen in alleviating
      menopausal symptoms.

PMID- 8538479
TI  - Effects of a new estrogen/progestin combination in the treatment of
      postmenopausal syndrome.
AB  - Postmenopausal women were randomly given either oral calcium (500 mg/day, control
      group, n = 12) or a combination of estradiol valerate (EV, 2 mg/day for 21 days)
      with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment
      cycle, n = 19). EV+CPA reduced (P < 0.01) postmenopausal complaints, inducing
      regular withdrawal bleeds, with no hysteroscopic or hystologic evidence of
      endometrial hyperstimulation after 12 months of treatment. In the control group,
      spine bone mineral density (BMD) and the total body bone mineral (TBBM) decreased
      (P < 0.01), whereas urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla
      Protein (BGP) and lipid profile did not show any significant modification
      throughout the study. In the EV+CPA group, urinary OHP/Cr and plasma BGP levels
      decreased (P < 0.01) after 6 and 12 months, whereas both BMD and TBBM showed a
      small but significant (P < 0.01) increase. In this group, LDL cholesterol
      significantly (P < 0.01) decreased and HDL levels significantly (P < 0.01)
      increased after 6 and 12 months. In conclusion, the EV+CPA combination is
      effective in relieving menopausal symptoms, produces a good cycle control and a
      favourable lipid profile, preventing postmenopausal bone resorption.

PMID- 8538480
TI  - Influence of two hormone replacement therapy regimens, oral oestradiol valerate
      and cyproterone acetate versus transdermal oestradiol and oral dydrogesterone, on
      lipid metabolism.
AB  - OBJECTIVE: To compare the influence on lipid metabolism of two discontinuous,
      sequentially combined hormone replacement therapy (HRT) regimens. STUDY DESIGN:
      In an open, randomized study in 60 women, a full lipid profile including Lp(a)
      and liver function tests were assessed in a fasting state at the end of treatment
      cycles 6 and 12. Group A was treated with 2 mg oestradiol valerate (days 1-21)
      sequentially combined with 1 mg cyproterone acetate (days 12-21); group B was
      treated with a patch releasing 50 micrograms oestradiol daily, twice a week (3
      weeks), sequentially combined with 20 mg dydrogesterone (days 12-21) orally.
      Statistical analysis by two-sided one-way analysis of covariance (covariable is
      baseline) for adjusted means of lipid parameters and rank transformation analysis
      for lipoprotein(a) (Lp(a)) was performed. RESULTS: Both groups were statistically
      comparable. The trial was completed by 45 subjects. Protocol violations occurred
      in 3 cases. Twelve subjects, equally divided between the groups, dropped out
      mainly because of adverse reactions. Both treatments were equally effective in
      the treatment of climacteric complaints. Liver function tests during the
      treatment period were normal in both groups. In group A, a statistically
      significant (P < 0.05) decrease versus baseline was observed in the serum levels
      (adjusted means) of the following parameters after 6 and 12 treatment cycles:
      total cholesterol (TC)-5% and -7%, respectively; low-density lipoprotein
      cholesterol (LDL-C) -13% and -14%, respectively; low-density lipoprotein
      cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) -16%
      and -18%, respectively. Triglycerides (TG) levels were significantly increased by
      28% and nearly significantly (P = 0.07) by 25% after 6 and 12 treatment cycles,
      respectively. In group B, all lipid parameters (with the exception of
      apolipoprotein A-II which was significantly decreased after 12 treatment cycles)
      remained unchanged during therapy. Statistically significant differences for all
      aforementioned variables were found between the groups after 6 and 12 treatment
      cycles, respectively, with the exception of TC after 12 treatment cycles. After 6
      treatment cycles, Lp(a) was decreased significantly (-18%) in group A as compared
      with baseline; after 12 months the decrease was -17% without reaching statistical
      significance. In group B, Lp(a) showed a slight but not statistically significant
      tendency to increase by 2% and 12% after 6 and 12 treatment cycles, respectively.
      Differences between both groups did not reach the level of significance.
      CONCLUSION: In this randomized, comparative study, a sequentially combined oral
      HRT regimen consisting of oestradiol valerate (2 mg daily on days 1-21) and
      cyproterone acetate (1 mg daily on days 12-21), induced a lipid pattern and
      probably also a change in Lp(a) levels, which is generally viewed to be more
      beneficial with regard to the prevention of cardiovascular disease than the lipid
      pattern induced by a sequentially combined regimen of transdermal 17 beta
      oestradiol (50 micrograms twice weekly during three weeks) and oral
      dydrogesterone (20 mg daily on days 12-21).

PMID- 8538481
TI  - Creatinine clearance at menopause is not related to bone mass in later life.
AB  - OBJECTIVE: To investigate whether creatinine clearance (Ccr) at menopause is
      related to bone mass later in life. METHODS: Ccr was measured within 5 years
      after natural menopause in two groups of normal women. Bone mineral content (BMC)
      of the distal forearm, lumbar spine, and proximal femur were measured by photon
      absorptiometry and dual energy X-ray absorptiometry in these women 6 years (n =
      47) and 14 years later (n = 98). RESULTS: Ccr corrected for body surface area
      just after the menopause did not correlate with BMC, 6.5 years and 14.5 years
      later. CONCLUSION: Low Ccr within the normal range at menopause is not an
      independent risk factor for osteopenia in later life.

PMID- 8538482
TI  - Postmenopausal osteoporosis: patient choices and outcomes.
AB  - OBJECTIVE: Only two medications, estrogen and injectable salmon calcitonin, are
      currently approved by the FDA for the treatment of osteoporosis. Oral etidronate
      has been investigated but not approved for osteoporosis therapy. We compared the
      three available anti-resorptive medications in untreated osteoporotic women.
      DESIGN: A nonrandomized, open label trial. After baseline biochemistry and bone
      mineral density (BMD) determinations, subjects self-selected therapy based on
      descriptions of the three drugs which were similar for all patients. Bone
      densitometry of the lumbar spine, femoral neck and distal and proximal forearm
      sites was repeated every 6 months. RESULTS: Twenty-one patients chose estrogen,
      20 chose etidronate and 11 chose calcitonin. Fear of breast cancer was the most
      common reason given for not choosing estrogen therapy. Mean age was slightly
      lower and spine and hip bone densities slightly higher in the estrogen group
      compared with both the etidronate and calcitonin groups. In the lumbar spine, all
      three agents resulted in similar small increments (mean increments 1.2-4.4% at 2
      years). In the estrogen group, there was no change in femoral neck density while
      there were significant losses in both calcitonin and etidronate groups (3.1
      4.9%). In the forearm, there was either no change (distal site) or an increment
      (proximal site) in the estrogen group, while both etidronate and calcitonin
      groups demonstrated a mean loss at both sites over the 2-year observation period.
      CONCLUSIONS: These preliminary results suggest that all three agents appear
      equally effective at maintaining or increasing BMD of the lumbar spine, while
      estrogen appeared more effective at maintaining or increasing BMD of the
      appendicular skeleton. This study underscores the need for an alternative to
      estrogen therapy which is equally effective and can be given orally for those in
      whom estrogen is either contraindicated or undesirable.

PMID- 8538483
TI  - Evidence that the loss of bone mass induced by GnRH agonists is not totally
      recovered.
AB  - There is disagreement as to whether the loss of bone mass induced by GnRH
      agonists is reversible. In part, the differences of opinion might be attributed
      to the fact that the influence of weight and seasonal changes on bone mass is
      often overlooked. Taking into consideration weight and seasonal changes in bone
      mass, total (TBBMC) and regional body bone mineral content were measured in 38
      women treated with GnRH agonists for 6 months for endometriosis or leiomyomata.
      Measurements were made at the onset of treatment, at 6 months of treatment and at
      6 months after finishing treatment. TBBMC was corrected for body weight. Body
      weight had increased significantly at 6 months of treatment (P = 0.0175).
      Regional bone mineral content showed the following: limbs, no changes; head,
      significantly lower at 12 months than at baseline (P = 0.0036) and at 6 months (P
      = 0.0343) of therapy; trunk, significantly lower at 6 months (P = 0.0002)
      compared to baseline, but the values at 1 year were not significantly different
      from either the baseline or the 6-month values; pelvis, the same pattern of
      change as in the trunk (P = 0.0349). TBBMC was significantly lower at 6 months of
      treatment (P < 0.0001) and at 1 year (P = 0.0162). TBBMC adjusted for weight
      experienced the same changes as unadjusted bone mineral content (P < 0.0001 and P
      < 0.0009 at 6 months and 1 year, respectively). Our findings indicate that the
      bone mass lost with GnRH treatment had not been restored 6 months after
      discontinuing treatment.

PMID- 8538484
TI  - Skin water-holding capacity and transdermal estrogen therapy for menopause: a
      pilot study.
AB  - The effects of menopause and hormone replacement therapy (HRT) on the epidermis
      are largely unknown. The aim of this study was to model and measure the influence
      of estrogen-transdermal HRT on subtle physiological changes taking place in the
      epidermis during the perimenopause. Skin capacitance and transepidermal water
      loss were measured both on normal-looking skin and at the site of a plastic
      occlusion stress test (POST). Two groups of 15 menopausal women were enrolled.
      One group was untreated and the other received transdermal estrogen. The water
      holding capacity of the stratum corneum was significantly increased at the POST
      site in women receiving transdermal estrogen. The improvement in the skin water
      holding capacity, which is known to be associated with a beneficial effect on the
      skin barrier function, may contribute to the prevention of several dermatoses.

PMID- 8538485
TI  - Changes in sex behaviour after menopause: effects of tibolone.
AB  - In order to analyse both sexual desire after menopause and its response to
      treatment with tibolone, a randomized placebo/tibolone trial has been designed
      with 28 postmenopausal patients. They were asked to answer a questionnaire
      designed by us to obtain quantitative measurements to describe changes in sexual
      desire. After selection, the patients were randomly assigned to two groups as
      follows: 14 in the group treated with 2.5 mg/day of tibolone and 14 in the
      placebo group treated with 500 mg/day of calcium. The patients were monitored
      after 3, 6 and 12 months. Before joining this study, they had signed a written
      consent. It was observed that the sexual desire after menopause underwent a
      significant fall, with decline in arousability and intercourse. The comparative
      results show that the patients treated with tibolone experience an improvement
      after the third month of treatment and this improvement was maintained until the
      end of treatment. We conclude that the questionnaire proposed here is a useful
      non-parametric method to diagnose a patient's sexuality status at the baseline
      assessment and a valuable tool for monitoring various therapies. Furthermore,
      tibolone proved to be effective in managing reduced sexual desire which appears
      in postmenopausal patients.

PMID- 8538486
TI  - Should women who have had breast cancer take hormone replacement therapy?

PMID- 8538487
TI  - A community-based study of menopause symptoms and estrogen replacement in older
      women.
AB  - This study examines the symptoms after a natural menopause recalled by women aged
      50-89 years. We determined the frequency and clustering of symptoms, the effect
      of age on symptoms, and the relation of symptoms to the use of estrogen therapy
      in a cross-sectional, community-based study of 589 Caucasian, middle- to upper
      middle-class women from Rancho Bernardo, California. At the time of menopause,
      55% of the women reported that they felt life was getting better and 57% were
      more cheerful. The most frequently recalled symptoms were hot flushes (74%),
      propensity to weight gain (45%), night sweats (35%), tiredness (32%), and
      insomnia (28%). Irritability was reported by one-fourth, depression by one-fifth.
      Nearly 11% reported anxiety about looking older. The recalled prevalence of hot
      flushes, irritability, weepiness and tiredness did not vary by current age, but
      younger women were significantly more likely than older women to have experienced
      night sweats, visible flushes, depression, anxiety about looking older and
      insomnia. Principal components factor analysis yielded four main independent
      factors: psychological symptoms (21% of the variance), vasomotor symptoms (14%),
      positive feelings (11%), and negative self-image (8%). The four symptom groupings
      suggest different causal mechanisms. Forty-two percent reported past, and 27%
      reported current use of estrogen therapy. Both past and current hormone users
      were significantly more likely to report menopause symptoms than non-users.
      Estrogen use was not associated with positive feelings or self-image at the time
      of menopause. Although three-quarters experienced symptoms, the majority of women
      reported positive feelings about menopause.

PMID- 8538488
TI  - Cross-sectional and case-controlled analyses of the association between smoking
      and early menopause.
AB  - To examine potential confounders and dose-response data for the association
      between smoking and menopause, we used both a cross-sectional and case-controlled
      approach. In total, 10,606 middle-aged women residing in eastern Massachusetts
      were surveyed about their age at menopause and smoking history; 344 women (cases)
      with natural menopause prior to age 47 and 344 age-matched women (controls) who
      were still menstruating or who had a menopause after age 46 were selected for
      further study. Risk for menopause was assessed by Kaplan-Meier, Cox proportional
      hazards, or logistic regression models. From cross-sectional data on 8657 women
      aged 45-54, the hazards odds ratio for a natural menopause among women who ever
      smoked compared to non-smokers was 1.31 (95% C.L. 1.21-1.42) and among women who
      had accumulated 30 or more pack-years was 1.87 (95% C.L. 1.67-2.04) after
      adjustment for parity and weight. An additional potential confounder from the
      case-controlled study was lower educational attainment, and after adjustment for
      this variable, significant trends persisted for risk of early menopause
      associated with age began smoking (P = 0.03), years of smoking (P = 0.01) and
      pack-years of smoking (P = 0.03). This study demonstrates an association between
      smoking and early menopause in both cross-sectional and case-controlled data that
      is not confounded by parity, weight, socio-economic status, or nutritional
      variables.

PMID- 8538489
TI  - Trends in the use of climacteric and postclimacteric hormones in Nordic
      countries.
AB  - The extent of menopausal and postmenopausal hormone use in Denmark, Finland,
      Norway, and Sweden during 1981-1992 was studied by means of drug sales figures
      and associations between hormone use, education, employment and occupational
      status, by questionnaire surveys in each of the respective countries in the 1980s
      90s. According to sales figures, hormone use has been different in each of the
      countries studied. In 1981 use was three times more common in Denmark than in
      Norway. In 1992 use had increased in all the other countries except Denmark, and
      was highest in Finland and Sweden. Based on 1981 data for Norway, on 1987 data
      for Denmark and on 1989 data for Finland, use of hormone therapy was related to
      education, employment or occupational status in Finland but not in Denmark or
      Norway. Differences in the phases of innovation diffusion between these countries
      may offer a partial explanation for these results.

PMID- 8538490
TI  - Compliance with long-term oral hormonal replacement therapy.
AB  - OBJECTIVE: To study long-term compliance with oral hormonal replacement therapy
      (HRT). METHODS: A total of 151 early postmenopausal women were initially randomly
      allocated to three groups in a double-blind, placebo controlled trial. Fifty
      women received continuous combined therapy, another 50 were placed on sequential
      therapy, while the remaining 51 women were given placebo for 2 years with no
      subsequent therapy. After 2 years of the trial, the women were followed in an
      open investigation for a total of 8 years. RESULTS: After 8 years, 112 (85%)
      women were interviewed. None of the women in the combined group had changed to
      other therapies (46% were still in treatment), 32% were still being treated with
      sequential therapy and 18% had changed to other HRTs (mainly because the women
      disliked the monthly bleeding induced). Of the placebo group, 18% had started HRT
      while 53% still did not receive any therapy. Of the women who had taken combined
      therapy for 5 years, 95% were still in therapy at the 8-year stage. Of the 25
      women who had taken sequential therapy for 5 years, 52% continued until the 8
      year stage and a further 16% received other types of HRT. The women who changed
      HRT switched to continuous combined therapy. CONCLUSION: The continuous combined
      treatment might provide an alternative to sequential treatment in postmenopausal
      women to achieve high long-term compliance.

PMID- 8538491
TI  - Partial DNA sequence of a beta-lactamase produced by a Shigella flexneri strain.
AB  - A probe was constructed by radioactive labelling, and enzymatically a DNA
      fragment of plasmid pMAM-1, which codes for a beta-lactamase in Shigella flexneri
      UCSM 129, was obtained by amplification of a small part of the gene using the
      polymerase chain reaction technique (PCR). Since previous published work
      indicated that this beta-lactamase was of the TEM type, the primers used to
      amplify the gene were two highly conserved DNA regions in all TEM beta
      lactamases. A 500 bp DNA probe was obtained which, by hybridization assays,
      facilitated the identification of restriction fragments of the plasmid containing
      the beta-lactamase gene. Two DNA fragments were sequenced by the Sanger method
      adapted to the PCR technique, and the sequence obtained showed a 100% homology
      with beta-lactamases TEM-1, TEM-2, TEM-13 and TEM-19. An intragenic restriction
      site, detected for Pst I, suggested that there is only one copy of the beta
      lactamase gene per plasmid copy.

PMID- 8538492
TI  - Correlation of teichoic acid D-alanyl esterification with the expression of
      methicillin resistance in Staphylococcus aureus.
AB  - Methicillin-susceptible and -resistant isolates of Staphylococcus aureus,
      including a teichoic acid-deficient mutant, were examined under varying
      physiological conditions for their degree of teichoic acid and lipoteichoic acid
      D-alanyl esterification. Methicillin-resistant strains grown in the presence of
      methicillin and NaCl possessed significantly decreased amounts of D-alanyl ester
      when compared with methicillin-susceptible isolates. These strains also exhibited
      reduced autolysis. An autoradiographic procedure was used to detect mutants,
      isolated by Tn917 and nitrosoguanidine mutagenesis of methicillin-susceptible
      strains, which were defective in D-alanyl ester formation. The quantitative
      uptake of D-[14C]alanine in these mutants was determined and the effect of
      methicillin on the growth and viability of each mutant was compared with the wild
      type strain. S. aureus mutant strains, defective in the uptake and incorporation
      of D-alanine, were shown to exhibit slightly reduced autolysis and an enhanced
      expression of methicillin resistance.

PMID- 8538493
TI  - A metallo-dependent cysteine proteinase of Cryptosporidium parvum associated with
      the surface of sporozoites.
AB  - A proteinase of 24 kD was found associated with sporozoites of Cryptosporidium
      parvum. Optimal hydrolysis of azocasein, casein, bovine serum albumin, and
      gelatin occurred at a pH of 6.5-7.0. Activity against azocasein was inhibited by
      ethylenediaminotetraacetic acid (EDTA), iodoacetic acid (IAA), trans
      epoxysuccinyl-L-leucylamido(4-guanido) butane (E-64), and phosphoramidon,
      suggesting that the enzyme was a metallo-dependent cysteine proteinase. Both
      serine and aspartate protease inhibitors failed to inhibit enzyme activity. The
      enzyme was partially purified by preparative isoelectric focusing of parasite
      membrane proteins. Polyclonal antiserum to parasite membrane proteins was
      generated in rats. The enzyme-containing fraction was subjected to SDS-PAGE and
      probed with antiserum, and the antibodies against the protease were eluted
      directly from nitrocellulose blots. An indirect immunofluorescence assay using
      these monospecific antibodies revealed that the protease occurred on the surface
      of sporozoites, but was not associated with oocyst walls, rhoptries, or
      micronemes.

PMID- 8538494
TI  - Population dynamics in the co-culture of Shigella flexneri 1b original strain and
      its antigenic 3b mutant carrying a prophage.
AB  - The antigenic mutant Shigella flexneri 3b showed selective prevalence when
      subcultured with the original strain 1b. Mathematical analysis of such co
      cultures showed that the dynamics of bacterial growth may be described by
      equations of the Lotka-Volterra type. The analysis of serial cultivations
      suggests that parameters of the equations may be realizations of random variables
      characterizing strains and media. The mutant carries a prophage lethal for the
      original strain. Distinctive features of the growth of these strains alone and in
      co-culture may be successfully explained by the differences in growth parameters,
      without phage inference. The concurrence model connected only with the existence
      of the phage is not sufficient. A complete description of the dynamics of the co
      culture is obtained by the connection of the assumptions of two models: strains
      in competition and growth of strains with phage, given the random character of
      the parameters.

PMID- 8538495
TI  - Application of an image analysis system to the quantitation of tumor perfusion
      and vascularity in human glioma xenografts.
AB  - A semiautomatic method based on a computerized digital image analysis system was
      developed to quantitate the perfused fraction of blood vessels and the relative
      vascular area in cross-sections of human glioma xenografts, implanted
      subcutaneously in athymic mice or intracerebrally in nude rats. The fluorescent
      dye Hoechst 33342 was injected intravenously to detect perfused tumor vessels. An
      immunofluorescent staining of Collagen type IV visualized the vascular structures
      in the same tumor section. Whole tumor sections were automatically scanned twice
      on a computer-controlled motorized stage of a fluorescence microscope under two
      different settings of the image analysis system. At the beginning of a scanning
      session an interactive routine was used to determine the threshold value for
      segmentation of vascular structures from the darker background. After the first
      scan a composite image was created, from the individually processed microscopic
      images, containing the detected vascular structures. The second scan yielded
      another composite image with objects representing the perfused areas. When both
      composite images were combined the overlapping structures showed the perfused
      vessels. Differences in perfused fractions and relative vascular areas were found
      between different tumors. The reproducibility of this analysis system was tested
      and evaluated. The method developed here provides a fast and accurate technique
      for simultaneous quantitative analysis of tumor perfusion and vasculature.

PMID- 8538496
TI  - Endogenous TNF-alpha modulates the proliferation of rat mesangial cells and their
      prostaglandin E2 synthesis.
AB  - Mesangial cells (MC) are one cellular source of tumor necrosis factor alpha (TNF)
      within the kidney as shown by experimental stimulation with endotoxin. TNF was
      shown to increase MC synthesis of prostaglandins E2 (PGE2) which down regulate MC
      proliferation. The involvement of endogenous TNF as an autocrine factor to
      control MC proliferation is unknown. This role was evaluated in vitro by addition
      of anti-TNF immunoglobulins and soluble TNF receptor-I (sTNF-RI) on rat MC. Anti
      TNF immunoglobulins and sTNF-RI induced a dose-dependent increase of cell
      proliferation when the cells were quiescent in 0.5% FCS P = 0.002). No effect was
      found when the cells were growing in 10% FCS (P = 0.113). Incubation of MC with
      anti-TNF immunoglobulins resulted in a dose-dependent decrease of PGE2 release.
      In order to investigate if the effect of TNF on MC proliferation was mediated by
      the decrease of PGE2 release, PGE2 was added to the culture medium at
      concentrations of 0.1 to 10 micrograms/ml in conjunction with anti-TNF
      immunoglobulins. PGE2 did not modify the proliferation induced by anti-TNF
      immunoglobulins. We conclude that anti-TNF immunoglobulins and sTNF-RI promoted
      MC DNA synthesis and influenced their PGE2 release by blocking the endogenous
      TNF. The mechanism of action on DNA synthesis was not mediated by PGE2. This
      indicates that endogenous TNF has a substantial role in the control of resting
      mesangial cells.

PMID- 8538497
TI  - Capillary reperfusion after L-arginine, L-NMMA, and L-NNA treatment in cheek
      pouch microvasculature.
AB  - The effects of arginine (L-arg), promoter of nitric oxide (NO) production and NO
      synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L
      arginine (L-NNA), on arteriolar responses and capillary perfusion after 30 min
      ischemia were studied in the cheek pouch preparation under pentobarbital
      anesthesia and intravenous drug infusion. Capillary density, venular leukocyte
      sticking, and vessel diameters were investigated by fluorescence microscopy.
      Damage due to photoactivation of intravascular dyes was investigated by injecting
      fluorescent dextran 150,000 MW prior to and after ischemia reperfusion. No
      difference was found indicating that effects were independent from exposure time
      to photoactivated dyes. Capillary perfusion reduction was always present after
      reperfusion in untreated, L-NMMA-treated, and L-NNA-treated animals, with
      increased venular leukocytes adhesion. Arteriolar vasomotion was induced by L
      NMMA treatment. Capillary perfusion recovered in L-arg-treated hamsters, where
      capillary blood flow velocity was lower than in L-NMMA group and the number of
      adhering leukocytes was lower than in untreated controls, L-NMMA, and L-NNA
      groups. It is concluded that L-arg determines perfusion with increased blood flow
      heterogeneity while inhibition of NO preserves capillary perfusion causing
      appearance of vasomotion in the arterial network.

PMID- 8538498
TI  - Lack of general correlation between interstitial fluid pressure and oxygen
      partial pressure in solid tumors.
AB  - Several studies have shown a decrease in blood perfusion and oxygen partial
      pressure (pO2), and an increase in interstitial fluid pressure (IFP) with
      increasing tumor size. However, it is not evident if the elevated IFP is a key
      parameter responsible for the poor perfusion and oxygenation of solid tumors. To
      this end, IFP and pO2 were measured in nine human tumor xenografts in
      immunodeficient mice at a fixed tumor size (approximately 250 mm3). IFP and pO2
      were also measured as a function of tumor volume in one human colon
      adenocarcinoma (LS174T) and in one human glioblastoma (HGL-9). In LS174T tumors
      IFP did not vary with size (P < .07); however, median pO2 decreased from
      approximately 35 mm Hg in 100-mm3 tumors to approximately 15 mm Hg in tumors of
      approximately 500 mm3 (P < 0.001). In HGL-9 tumors an inverse correlation between
      IFP and pO2 was found; IFP increased (P < 0.001) and pO2 decreased (P < 0.001)
      with increasing tumor size. At a fixed tumor size of 250 mm3 no correlation was
      found between mean IFP and median pO2 (P < 0.5) or between the mean IFP and the
      hypoxic fraction (pO2 < 2.5 mm Hg) (P < 0.7) in the nine tumors studied. The
      absence of a general relationship between IFP and pO2 could result in part from
      differences in vascular resistance between tumors. For example, a high geometric
      resistance to blood flow on the arterial side will lead to a low IFP and blood
      flow, whereas an elevation of the venous resistance will reduce blood flow and
      increase IFP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538499
TI  - Measurement of membrane potential of endothelial cells in single perfused
      microvessels.
AB  - The membrane potential is an important modulator of calcium ion flux into
      endothelial cells of venular microvessels. We developed a method to measure the
      membrane potential of endothelial cells forming the walls of individually
      perfused microvessels under the same experimental conditions as those used to
      measure cytoplasmic calcium concentration and microvessel permeability. The
      membrane potential-sensitive fluorescent dye, bis-oxonol (1 microM), was added to
      the perfusate and the changes in bis-oxonol fluorescence intensity (FI) were
      calibrated in terms of changes in membrane potential using the cationic
      ionophore, gramicidin. FI changes an average of 0.625% per millivolt. The resting
      membrane potential of endothelial cells measured in single perfused microvessels,
      each calibrated individually, was 51.6 +/- 4.9 mV (n = 9). In the presence of
      high potassium Ringer's solutions (57.9 and 100 mM, [K+]o), the membrane
      depolarized 25 +/- 3 and 40 +/- 5 mV, respectively. Conversely, low potassium
      solutions (0.1 mM [K+]o) hyperpolarized the membrane by 23 +/- 4 mV. The
      endothelial membrane was also depolarized when the Na-K-ATPase was inhibited with
      ouabain. This method provides new data to test current hypotheses describing the
      role of the endothelial cell membrane potential as a modulator of microvessel
      permeability.

PMID- 8538500
TI  - Quantitative differences in neoglycoprotein binding for vascular endothelial
      cells from porcine brain, ovary, and testis in vitro.
AB  - Carrier-immobilized carbohydrates are valuable tools for assessing the
      glycoligand-binding capacity of cell surfaces. A panel of 10 types of fluorescent
      neoglycoproteins has been synthesized to determine the extent of their specific
      binding to endothelial cells in vitro that have been obtained from porcine brain,
      ovary, and testis. Different sugar moieties revealed a nonuniform capacity to
      bind to the endothelial cells as determined by flow cytometric analysis, the
      histogenetic origin of the preparations being an important factor. Binding of
      mannose, xylose, and glucuronic acid was especially pronounced, but the extent of
      cell-associated fluorescence was significantly different dependent on the source
      of the endothelial cells. These results clearly reveal that endothelial cells in
      vitro display the capacity to specifically recognize defined carbohydrate
      moieties. Moreover, endothelial cells of different tissue origin can exhibit
      variability in this property, potentially endowing this cell type with site
      dependent molecular properties.

PMID- 8538501
TI  - Validation of collagenous protein synthesis as an index for angiogenesis with the
      use of morphological methods.
AB  - A method providing a biochemical index for the evaluation of promoters or
      inhibitors of angiogenesis in the chick chorioallantoic membrane (CAM) is here
      described and validated. This method is based on the determination of collagenous
      protein synthesis which takes place during new vessel formation. Validation was
      done by comparing collagenous protein synthesis to morphological methods of
      determining vascular density either by counting the number of vessels
      intersecting three concentric rings or by computer-assisted image analysis. Five
      compounds which promote or inhibit angiogenesis in the CAM were used for this
      purpose. The protein kinase C activator 4-beta-phorbol 12-myristate 13-acetate
      and alpha-thrombin increased collagenous protein synthesis and these results
      correlated with those obtained by using the two morphological methods mentioned
      above. Similarly, the inhibitors of angiogenesis, Ro318220, tricyclodecan-9-yl
      xanthate (D609), and 8,9-dihydroxy-7-methyl-benzo[b]quinolizinium bromide
      (GPA1734), reduced collagenous protein synthesis and vascular density (determined
      by image analysis or by counting the number of vessels intersecting three
      concentric rings) to a comparable degree. These results indicate that collagenous
      protein synthesis can be used as a reliable, reproducible, and unbiased index of
      angiogenesis in the chick chorioallantoic membrane.

PMID- 8538502
TI  - Platelet activating factor modulates microvascular permeability through nitric
      oxide synthesis.
AB  - Biochemical signaling determines the specific action of vasomediators in the
      control of microvascular permeability and tone. We tested the hypothesis that
      nitric oxide (NO) synthesis is involved in the biochemical signaling pathway of
      platelet activating factor (PAF). The cheek pouch of anesthetized male Syrian
      hamsters was used as a microvascular model. Vessel diameter [expressed as the
      ratio of the experimental to the control (e/c) diameter, with control diameter
      normalized to 1] and extravasation of FITC-dextran 150 by integrated optical
      intensity (IOI) were determined using intravital fluorescent microscopy and
      computer-assisted digital image analysis. N-Nitro-L-arginine methyl ester (L
      NAME) at 10(-5) and 10(-6) M and N-nitro-L-mono-methyl arginine (L-NMMA) at 10(
      4) and 10(-5) M were used as inhibitors of NO synthase (NOS). Acetylcholine (ACh)
      and bradykinin were used as indirect indices of NOS activation. L-NAME and L-NMMA
      attenuated both ACh and bradykinin vasodilatory effects as well as the bradykinin
      induced increase in vascular permeability. Topical PAF (10(-7) M) caused
      vasoconstriction (mean +/- SEM e/c ratio = 0.3 +/- 0.1) and increased IOI from a
      normalized baseline of 0 to 67.4 +/- 12.8. Topical administration of L-NAME
      produced differential effects on the series-arranged arterioles but had no effect
      on postcapillary venular permeability. L-NMMA did not influence the basal
      arteriolar diameter, but at 10(-5) M it caused a small increase in permeability
      (IOI = 14.3 +/- 4.2). In the presence of NOS inhibitors, PAF caused a reduced
      arteriolar constriction (e/c ratio = 0.6 +/- 0.1) relative to PAF alone. Both NOS
      inhibitors reduced the PAF-stimulated increase in vasopermeability. At 10(-5) M L
      NMMA, the PAF-stimulated IOI mean value was 26.1 +/- 5.2, while at 10(-4) M L
      NMMA the PAF-stimulated IOI was 15.2 +/- 2.6 compared to 10(-7) M PAF (67.4 +/-
      12.8). These results support our hypothesis that NO synthesis is a step in the
      biochemical signaling pathway of the postcapillary cellular responses to PAF.

PMID- 8538503
TI  - Effect of increased duration of high perfusion pressure on stress failure of
      pulmonary capillaries.
AB  - We have previously shown that raising the capillary transmural pressure (Ptm) in
      rabbit lung causes disruption of the capillary endothelium, alveolar epithelium,
      or sometimes all layers of the wall. In those studies the lungs were perfused
      with autologous blood (1 min), then saline/dextran (3 min), followed by
      glutaraldehyde fixative (10 min), all at the same pressure. The present study was
      designed to determine whether increasing the time of exposure of the capillaries
      to the increased pressure altered the frequency of stress failure. The procedure
      was identical to that of the previous study except that the duration of the blood
      perfusion was extended from 1 to 10 and 100 min. We chose a Ptm of 32.5 cm H2O
      because our previous studies showed that this caused only a few disruptions per
      millimeter endothelial and epithelial boundary length (0.7 +/- 0.4 and 0.9 +/-
      0.6 (SE), respectively). Ten New Zealand white rabbit lungs were perfused with
      autologous blood plus homologous blood from additional rabbits for 10 and 100
      min. After 100 min of blood perfusion the number of disruptions per millimeter
      endothelial and epithelial boundary length (0.66 +/- 0.4 and 0.52 +/- 0.33 (SE),
      respectively) was not significantly different from the earlier study. Thus,
      increasing the duration of the increased Ptm during blood perfusion by 100-fold
      did not alter the incidence of stress failure. These results indicated that any
      viscoelastic behavior resulting in further strain and ultimately failure of the
      capillary walls is insignificant over a wide range of exposure times to increased
      pressure under the conditions of this study.

PMID- 8538504
TI  - Evidence that the L-arginine pathway plays a role in the regulation of pumping
      activity in bovine mesenteric lymphatic vessels.
AB  - The objective of this study was to investigate the role of the L-arginine pathway
      in the regulation of lymphatic pumping. Bovine mesenteric lymphatic vessels (8 to
      12 cm in length containing four to six lymphangions) were immersed in an organ
      bath with input provided by a reservoir filled with Krebs solution. The vessels
      were stimulated to pump by applying a 6 cm H2O transmural pressure. The addition
      of 10(-7)-10(-4) M oxyhemoglobin, NG-monomethyl-L-arginine (L-NMMA), or methylene
      blue to the reservoir resulted in a reduction in lymphatic pumping. L-Arginine
      (10(-7)-10(-4) M) had no effect on spontaneous pumping activity. However, L
      arginine reversed the inhibition caused by oxyhemoglobin and L-NMMA. When tested
      between 10(-7) and 10(-6) M, sodium nitroprusside (sNP) had variable effects on
      lymphatics. sNP depressed pumping in approximately 2/3 of the vessels and
      increased pumping in the remaining 1/3 of ducts. When the results were meaned,
      sNP caused a significant depression in activity. However, the lower concentration
      of sNP (10(-7) M) was able to reverse the inhibitory effects of oxyhemoglobin, L
      NMMA, and methylene blue whereas the higher concentration (10(-6) M) caused
      further reductions in pumping activity. These results suggest that bovine
      lymphatic vessels produce nitric oxide or a related compound. L-Arginine
      metabolites appear to facilitate the pumping response by an as yet undefined
      mechanism.

PMID- 8538505
TI  - The mechanics of arteriole-tissue interaction.
AB  - Arterioles are embedded in the extensive connective tissue matrix of the
      interstitium. Mechanical interactions with the interstitium may affect the length
      tension characteristics of arterioles, and thus affect their reactivity. However,
      no studies have adequately characterized the coupling between arterioles and the
      interstitium or investigated how the interstitium might change the physiological
      expression of arterioles. Therefore, the goal of this project was to investigate
      the mechanical interactions between arterioles and the interstitium and then to
      predict the physiological consequences of these interactions. We measured in situ
      the mechanical coupling of arterioles to the interstitium, the mechanical
      properties of the interstitium, and the structure of the interstitium in the
      hamster cheek pouch. We demonstrated that there are mechanical interactions
      between arterioles and the interstitium that are mediated both through direct
      connections and through the movement of extracellular fluid through the
      connective tissue network. We also found that the elastic modulus of the
      interstitium increases in the vicinity of the arteriole. Finally, both the
      mechanical coupling of arterioles to the interstitium and the mechanical
      properties of the interstitium are explained by the structure of the connective
      tissue matrix. The arterioles appear to be connected to adjacent fibroblasts and
      fibrocytes by collagen fibrils. These cells are in turn connected to the fiber
      matrix of the interstitium. Furthermore, the presence of these cells may explain
      the mechanical heterogeneity of the interstitium. We propose that the
      physiological role of the interstitium surrounding arterioles is to protect
      arterioles from stretching and deformation of the tissue while allowing these
      vessels to constrict freely.

PMID- 8538506
TI  - Effect of leukocytes and platelets on blood flow through a parallel array of
      microchannels: micro- and macroflow relation and rheological measures of
      leukocyte and platelet activities.
AB  - The effect of leukocytes and platelets on the flow of blood through a parallel
      array of identical microchannels (equivalent diameter 6 microns, equivalent
      length 20 microns, number 2600) was examined by microscopy and total flow rate
      under constant suction (20 cm H2O). Fresh heparinized whole blood was used for
      the measurement with dilution by autologous plasma to give leukocyte counts 1200
      1300/microliters or platelet counts 45,000-50,000/microliters. Despite the
      uniform flow conditions, cells treated with 1-10 nM FMLP or 0.1-1 microM ADP
      produced large temporal and spatial (channel to channel) variations in the flow
      by their transient blocking of the channels. The irregular flow was further
      accentuated by concomitant aggregation of erythrocytes. However, no fluctuations
      were observed in the total flow rate of blood, which decreased exponentially with
      time or with blood volume that had passed through the channels and approached a
      constant value despite a continual increase in erythrocyte aggregation.
      Furthermore, the flow curve pattern, i.e., an exponential approach to a steady
      state, appeared to be independent of both the structural details of the
      microchannels and the degree of blocking within the microchannels. This suggests
      that the total flow rate shows a statistical mechanical behavior, i.e., a
      relaxation process of a macrosystem composed of identical microscopic components
      that fluctuate independently of each other. Phenomenological parameters (rate
      constants of blocking and reopening of the microchannels) which can describe the
      observed flow curves depended on the stimulant does and also differed between
      different subjects, and hence appear to be useful as measures of leukocyte and
      platelet activities related to their rheology.

PMID- 8538507
TI  - Michigan Supreme Court races: physician involvement key.

PMID- 8538508
TI  - What effect are women physicians having on the practice of medicine in Michigan?
      It depends on who you ask.

PMID- 8538509
TI  - Physician wellness target of MSMS Committee.

PMID- 8538510
TI  - [Effect of membranotropic physiologically-active substances on the growth of
      Saccharomyces cerevisiae cultures].
AB  - The effect of Bacillus intermedius RNase and yeast autoregulatory d2 factor on
      growth of Saccharomyces cerevisiae is reported. It is shown that 0.01
      microgram/ml of RNase stimulates the growth of the yeast on malt wort and
      molasses, the peak of the effect being observed for the enzyme added in the
      middle exponential phase. Certain concentrations of the d2 factor can also
      potentiate yeast growth. The effect is more pronounced if the d2 factor and RNase
      are added in combination rather than singly. Although the cell membrane is a
      target for both d2 factor and RNase, the mechanisms of their action are
      presumably different.

PMID- 8538511
TI  - [Biosynthetic regulation of extracellular ribonucleases in native strains of
      bacilli and in recombinant strains of Escherichia coli].
AB  - Regulation of the biosynthesis of extracellular ribonucleases of Bacillus
      amyloliquefaciens H2 (barnase), Bacillus intermedius 7P (binase), and Bacillus
      pumilus KMM 62 (RNase Bp) was studied in their native strains and recombinant
      Escherichia coli strains. Recombinant plasmids were obtained that contained genes
      encoding barnase, binase, and RNase Bp under the control of their own regulatory
      sequences (plasmids pMT415, pML5, and pML61), genes encoding barnase and binase
      under the control of the tac promoter and the phoA leader sequence (plasmids
      pMT416 and pML163), and the binase-encoding gene under the control of the
      regulatory sequences of the barnase and RNase Bp genes (plasmids pML53 and pML67,
      respectively). Inorganic phosphate (Pi) inhibited the biosynthesis of binase and
      RNase Bp in natural strains B. intermedius 7P and B. pumilus KMM 62 and
      recombinant E. coli strains when genes encoding these RNases were under the
      control of their own regulatory sequences. In contrast the biosynthesis of
      barnase-either in the natural B. amylolique-faciens strain or in recombinant E.
      coli strains-was not affected by Pi. Neither did inorganic phosphate produce any
      effect on the biosynthesis of binase when the binase-encoding gene was under the
      control of the barnase gene promoter (pML53). The leader sequences and promoters
      were found to be similar in the binase and RNase Bp genes and differed
      considerably from the leader sequence and promoter of the barnase gene. The
      promoter regions of the binase and RNase Bp genes, but not of the barnase gene,
      contained sequences that resembled the Pho box of the phosphate regulon from E.
      coli.

PMID- 8538512
TI  - [Biosynthesis of alkaline extracellular proteinases in Bacillus intermedius].
AB  - The conditions for growth and serine proteinase biosynthesis were studied in the
      batch culture of Bacillus intermedius. The synthesis of the enzyme was found to
      be inhibited by glucose and by the amino acid mixture and activated by the
      addition of organic compounds-casein and gelatin-to the medium. Inorganic
      phosphate in the medium increased the enzyme yield. The enzyme activity was shown
      to be twofold higher upon the addition of corn extract (1.8%) in the medium than
      in the medium with meat peptone (1.7-2.2%) and inorganic phosphate (0.28-0.30
      miligram).

PMID- 8538513
TI  - [Mechanism of reactivating Escherichia coli inactivated by ultraviolet light with
      cell extracts of propionic acid bacteria].
AB  - Two mechanisms of reactivation of UV-inactivated Escherichia coli cells-
      photoreactivation (PhR) and reactivation by the dialysates of propionic acid
      bacteria--are shown to be different but not completely additive. PhR displays an
      insignificant negative effect on the reactivation by active substances (peptides)
      of the dialysate, whereas reactivation by dialysate inhibits PhR. The maximal
      reactivation can be attained under complete PhR followed by the protective action
      of dialysate. The dialysate protects UV-irradiated E. coli cells with PolA, UvrA,
      and RecA mutations and Salmonella typhimurium TA 100 (UvrB) cells and also exerts
      an antimutagenic effect on S. typhimurium TA 100. Protection by dialysate is
      suggested to be due to restoration of the cell division mechanism damaged by UV
      irradiation.

PMID- 8538514
TI  - [Creation and practical use of a mathematical model of the antagonistic action of
      bacilli in designing probiotics].
AB  - A major problem in constructing probiotics, preparations based on antagonistic
      action of live cultures of saprophytic bacteria, is finding antagonist strains
      with the required properties. A candidate strain must produce antagonistic action
      against a given set of pathogens, show high resistance to adverse environmental
      conditions, and be harmless for the macroorganism. Screening for such strains is
      a prolonged and laborious procedure.

PMID- 8538515
TI  - [Determining the concentration of eukaryotic cells by their integral
      fluorescence].
AB  - A proportional relationship was established between the total luminescence
      intensity of eukaryotic cells trapped on membrane filters and stained with
      fluorescent dyes and the number of cells present on the specimen area
      corresponding to the size of the cytofluorometric unit probe. An integral
      fluorescent method was developed that allows determination of the concentration
      of somatic cells in milk samples with the help of a calibration curve constructed
      on the basis of counting yeast cells. The method allows determination of the cell
      concentration in a 1 x 10(5)-5 x 10(6) cells/ml range. The results obtained using
      the integral fluorescent method are compared with data of direct visual count and
      with readings of the automatic FOSSOMATIK device.

PMID- 8538516
TI  - If it's the virus, why aren't we measuring it?

PMID- 8538517
TI  - Diagnosis of deep vein thrombosis.

PMID- 8538518
TI  - Slip, slop, slap and wrap. Should we do more to prevent skin cancer?

PMID- 8538519
TI  - Treating solid tumours with high dose chemotherapy.

PMID- 8538520
TI  - Colour-assisted compression ultrasound in the diagnosis of calf deep venous
      thrombosis.
AB  - OBJECTIVE: To determine sensitivity and specificity of colour-assisted
      compression ultrasound (CUS) in the diagnosis of deep venous thrombosis (DVT)
      isolated to the calf veins. DESIGN: Prospective comparison of CUS with contrast
      venography in patients undergoing both procedures, with blinded evaluation of
      results. SETTING: Alfred Hospital, Melbourne (an urban tertiary referral
      hospital), between November 1990 and May 1992. SUBJECTS: Patients presenting for
      contrast venography with signs or symptoms of lower limb DVT. OUTCOME MEASURES:
      Presence of DVT; technical adequacy of examination. RESULTS: 92 of 402 patients
      (104 limbs) were examined. DVT was detected by venography in 43 limbs and was
      isolated to the calf veins in 19. It was diagnosed by CUS for eight of these 19.
      Calf CUS was technically inadequate in 26 limbs. Sensitivity and specificity of
      CUS for isolated calf DVT were 67% (95% confidence interval [CI], 40%-94%) and
      93% (95% CI, 83%-100%), respectively, when the CUS was adequate. The low
      sensitivity of CUS was related to small size of the thrombi, inadequate studies
      because of previous DVT or very swollen limbs and technical errors. CONCLUSION:
      CUS is accurate for detecting larger isolated calf DVT when the calf study is
      adequate. Including the calf veins as well as the femoropopliteal veins in the
      initial CUS examination for symptomatic suspected lower limb DVT may reduce the
      need for follow-up CUS.

PMID- 8538521
TI  - Changes in cancer incidence and mortality in New South Wales.
AB  - OBJECTIVE: To assess changes in cancer incidence and mortality in New South Wales
      (NSW) between 1973-1977 and 1988-1992. DESIGN: Descriptive analysis of statutory
      cancer notifications to the NSW Central Cancer Registry. OUTCOME MEASURES: Age
      standardised incidence and mortality rates calculated with the "world" standard
      population. RESULTS: Overall cancer incidence rose markedly, from 251 to 318 per
      100,000 in men and from 202 to 241 per 100,000 in women. The rise was greatest in
      the 60-and-over age group. Cancer mortality fell marginally in men (from 166 to
      162 per 100,000) and did not change in women (100 per 100,000 in both periods).
      It fell in the under-60 age group, and remained stable or rose in older people.
      Prostate and breast cancers and melanoma of the skin accounted for about half the
      increase in incidence. Both incidence and mortality increased significantly (P <
      0.01) for melanoma and non-Hodgkin's lymphomas in men and lung cancer in women,
      and fell substantially for stomach cancer in both sexes, lung cancer in men and
      cervical cancer in women. Despite increasing incidence, mortality, also fell for
      testicular cancer in men and rectal cancer in women and for leukaemias in
      children. CONCLUSIONS: The major factor causing the increased incidence of
      overall cancer was earlier detection. Altered exposure to risk factors could be
      identified for only a minority of the changes.

PMID- 8538522
TI  - Deception and self-harm in the quest for freedom: an audit of Vietnamese boat
      people admitted to a regional hospital in Hong Kong.
AB  - OBJECTIVES: To document the medical problems of detained Vietnamese boat people
      admitted to hospital in Hong Kong, and to identify the medical problems or
      features that may indicate an intention to abscond. DESIGN AND SETTING: A
      retrospective review of the records of all Vietnamese boat people admitted to the
      Medical Unit of the Prince of Wales Hospital, Hong Kong, between 1 October 1993
      and 30 September 1994. RESULTS: 614 Vietnamese boat people were admitted during
      the 12 months (comprising 3% of total admissions). 92 (15%) of these absconded
      from hospital after admission (compared with 0.06% for all other admissions).
      Gastrointestinal bleeding, clinical sepsis, drug overdose and spontaneous
      pneumothorax were the most common presentations among those who absconded. One
      third (33.8%) of the 80 patients whose symptoms indicated gastrointestinal
      bleeding had insignificant endoscopic findings. Needle puncture marks were found
      in nine of the 75 patients with unexplained bacteraemia and in five of the 12
      patients with spontaneous pneumothorax. CONCLUSIONS: Clinicians who provide
      medical care to Vietnamese boat people should be aware of the high incidence of
      absconding from hospital and that self-inflicted injuries are not uncommon and
      may identify intending absconders.

PMID- 8538523
TI  - Impact of laparoscopic cholecystectomy in a major teaching hospital: clinical and
      hospital outcomes.
AB  - OBJECTIVE: To compare the clinical, training and cost implications of
      laparoscopic cholecystectomy with open cholecystectomy. SETTING: A university
      teaching hospital. DESIGN: A retrospective review of all patients who underwent
      cholecystectomy in 1989, before the introduction of the laparoscopic technique,
      and in 1993, after the learning curve for laparoscopic cholecystectomy had been
      overcome. MAIN OUTCOME MEASURES: Surgical indications, feasibility of
      laparoscopic approach, type of surgeon, operating time, hospital stay,
      postoperative complications, and cost analysis. RESULTS: 240 cholecystectomies
      were performed in 1989 and 293 in 1993. This is a 22% increase in overall
      workload and includes a significant increase (85%; P < 0.0001) in elective
      caseload. In 1993, 89% of patients underwent laparoscopic surgery, with
      conversion to open cholecystectomy in 6.8% of elective patients and 33% of
      emergency patients. Surgical indications remained the same, as did the time from
      diagnosis to cholecystectomy. There were significant changes in median length of
      hospital stay (from 10 days in 1989 to 4 days in 1993; P < 0.0001), successful
      intraoperative cholangiography (93% versus 73%; P < 0.0001), and exploration of
      the common bile duct (15% versus 5% of patients; P = 0.0005). The number of
      cholecystectomies performed by surgeons-in-training decreased from 65% to 40%,
      individual treatment costs were reduced by 62% and overall hospital costs were
      reduced by 53%. Complications fell from 12% to 7% (P = 0.07), with the only major
      bile duct injury occurring in 1989. There were three deaths in 1989 and two
      deaths in 1993. All deaths followed open surgery. CONCLUSIONS: Laparoscopic
      cholecystectomy is associated with improved patient outcomes and, despite the
      increased workload, significant savings for hospitals.

PMID- 8538524
TI  - Wernicke-Korsakoff syndrome in Sydney hospitals: before and after thiamine
      enrichment of flour.
AB  - OBJECTIVE: To estimate the incidence of Wernicke-Korsakoff syndrome (WKS) before
      and after the introduction of thiamine enrichment of bread flour in 1991. DESIGN:
      Retrospective survey of hospital records. Patient records with the diagnostic
      codes for Wernicke's encephalopathy (WE) or Korsakoff's psychosis (KP) were
      reviewed and details of acceptable cases were entered onto a data form. SETTING:
      All 17 major public general hospitals in the Sydney area (New South Wales),
      between 1978 and 1993. OUTCOME MEASURES: Numbers of confirmed or probable
      diagnoses of WE, KP or WKS and associated deaths, patient demographic and social
      characteristics and alcohol intake. RESULTS: 1,267 patients with WKS were found,
      with 1,012 acute cases. Although numbers of acute cases may have started to fall
      before 1991, numbers for the last two years were the lowest of all the 16 years
      (P = 0.004). Cases of KP outnumbered those of WE by about 3:1 and men outnumbered
      women 4:1. The peak age was 60-64 years (17%) and beer was the most commonly
      cited alcoholic drink (71%). The red-cell transketolase test was seldom used for
      diagnosis (3% of acute cases). CONCLUSIONS: The lower number of "acute" cases in
      1992 and 1993 is consistent with a preventive effect of mandatory enrichment of
      bread with thiamine, but is not conclusive evidence. Longer follow-up of Sydney
      hospitals, results of postmortem examinations and follow-up in other areas of
      Australia are required.

PMID- 8538526
TI  - Current strategies for hormone replacement therapy for the hypopituitary patient.

PMID- 8538525
TI  - Laparoscopic cholecystectomy: what national benefits have been achieved and at
      what cost?
AB  - Changes in the practice of surgery following the introduction of laparoscopic
      cholecystectomy (removing asymptomatic gallstones, duplicating procedures for
      diagnosing and managing common bile duct stones, and deferring laparoscopic
      management of complicated gallstones) as well as the increased rate of
      complications (particularly duct injury), have eroded the economic benefits to
      health care funders of shorter hospital stays. However, these benefits may be
      achieved if laparoscopic procedures are performed only by experienced surgeons
      and if the procedure is offered to all patients with gallstones, including
      complicated cases. Benefits to the community remain in terms of productivity
      savings as a result of an earlier return to work for patients.

PMID- 8538527
TI  - Are non-allergenic environmental factors important in asthma?
AB  - OBJECTIVE: To review the roles of viral respiratory tract infections,
      environmental tobacco smoke and air pollution in asthma. DATA SOURCES: MEDLINE
      (1992-1995) searches were conducted for publications on asthma, environmental
      tobacco smoke, ozone, nitrogen dioxide and particulates. STUDY SELECTION:
      Representative original experimental and epidemiological studies and reviews of
      viral infections in asthma. DATA SYNTHESIS: Respiratory virus infections are the
      most common and important trigger of asthma attacks in children and probably also
      in adults. Their role in promoting development of asthma is not so clear.
      Exposure to environmental tobacco smoke is almost certainly responsible for some
      cases of childhood asthma, and can also trigger symptoms of bronchoconstriction
      in adults with asthma. Exposure to ozone or nitrogen dioxide is associated with
      symptoms, impaired lung function, bronchial hyperresponsiveness and hospital
      presentations for asthma. These pollutants may also act as cofactors in the
      development of allergen-specific bronchial hyperresponsiveness. CONCLUSIONS:
      Research on preventing upper respiratory viral infections may reduce asthma
      morbidity. The move to non-smoking workplaces is welcome, but new interventions
      are needed to prevent young women taking up smoking and subsequently exposing
      their children. The ambient air quality guideline for ozone should be revised and
      a health-based guideline for respirable particulates introduced.

PMID- 8538528
TI  - Managing early breast cancer.

PMID- 8538529
TI  - Q fever cluster in the southern tablelands district of NSW.

PMID- 8538530
TI  - Tattoo parlours and hepatitis C virus infection.

PMID- 8538531
TI  - Results from a skin cancer screening program in Western Australia.

PMID- 8538532
TI  - High and low roads to aboriginal health.

PMID- 8538533
TI  - The euthanasia controversy. Decision-making in extreme cases.

PMID- 8538534
TI  - Somatisation disorder: a major public health issue.

PMID- 8538535
TI  - Somatisation disorder: a major public health issue.

PMID- 8538536
TI  - The use of controlled release morphine sulfate (MS Contin) in Queensland 1990
      1993.

PMID- 8538537
TI  - Ivermectin and crusted (Norwegian) scabies.

PMID- 8538538
TI  - Canada's Red Cross Society recalls plasma because of possible Creutzfeldt-Jakob
      disease contamination.

PMID- 8538539
TI  - Screening for diabetic retinopathy.

PMID- 8538540
TI  - World AIDS Day: what progress since last year?

PMID- 8538541
TI  - Voice from the Pacific. A plea for public health support.

PMID- 8538542
TI  - Hospitals, doctors and telephones.

PMID- 8538543
TI  - Climate change and global infectious disease threats.
AB  - The world's climate is warming up and, while debate continues about how much
      change we can expect, it is becoming clear that even small changes in climate can
      have major effects on the spread of disease. Erwin K Jackson, a member of
      Greenpeace International's Climate Impacts Unit and a delegate to the 11th
      session of the United Nations Intergovernmental Panel on Climate Change (Rome, 11
      15 December), reviews the scientific evidence of this new global threat to
      health.

PMID- 8538544
TI  - The ozone hole.

PMID- 8538545
TI  - Skin cancer and the ozone hole. When is not enough likely to be too much?

PMID- 8538546
TI  - Success of surf lifesaving resuscitations in Queensland, 1973-1992.
AB  - OBJECTIVE: To determine the success of resuscitations performed by Queensland
      surf lifesavers and the factors associated with successful resuscitation. DESIGN:
      Retrospective case survey, using data from Surf Life Saving Association of
      Australia resuscitation report forms. SETTING: 54 Queensland beaches patrolled by
      surf lifesavers, and nearby areas, between 1973 and 1992. OUTCOME MEASURES:
      Reasons and success rates for resuscitation, distance from surf clubhouse,
      whether inside patrolled area, victim's age, sex, facial colour on presentation,
      occurrence of vomiting, airway difficulties and involvement of alcohol. RESULTS:
      171 resuscitations were reported (80% involving males and 20% females), with a
      success rate of 67%. Seventy-two per cent were performed during patrol hours, 17%
      within patrolled areas (95% successful) and 55% outside patrolled areas (only 62%
      successful) (P = 0.004 for difference in success rates); resuscitation success
      rates fell with increasing distance from the surf clubhouse (P = 0.009). Reasons
      for resuscitation were: immersion, 70% (success rate, 68%); collapse, 22%
      (success rate, 47%); and surf or beach injury, 7% and 1%, respectively (success
      rate, 100% for each). Resuscitation was more likely to be successful if the
      victim's facial colour on presentation was normal, pale or blue, but not if grey,
      and if the victim did not vomit or regurgitate. CONCLUSIONS: Resuscitation by
      surf lifesavers was highly successful when the victim was close to the surf
      patrol, indicating a need for funding to expand patrol areas. Public awareness of
      the greater safety of "bathing between the flags" (in the delineated patrol area)
      should be increased.

PMID- 8538547
TI  - An unusual case of cyclical abdominal pain.

PMID- 8538548
TI  - Liquid nitrogen: how to make it last.
AB  - AIM: To compare the rate of heat flow into two vacuum flasks with vacuum
      envelopes of different materials (glass and stainless steel). DESIGN: Prospective
      non-randomised comparison (n = 2). SETTING: Home (edge of the Great Sandy
      Desert), Sunday. OUTCOME MEASURE: Change in liquid nitrogen content over time.
      RESULTS: Within eight hours, the flask with a stainless steel envelope lost
      almost all its nitrogen (about 800 g), while the flask with a glass envelope lost
      only about 100 g. The stainless steel flask therefore had a heat leakage rate
      about eight times that of the glass flask. CONCLUSION: A glass-lined vacuum flask
      is better for keeping liquid nitrogen cold (and coffee hot) than a steel-lined
      flask.

PMID- 8538549
TI  - The Chocuhaler: sweet deliverance in asthma management.
AB  - OBJECTIVE: To determine the characteristics of a new cocoa-based edible spacer
      device for the delivery of aerosol bronchodilator. DESIGN: In-vitro comparison of
      two spacer devices (standard and edible) and determination of bronchodilator
      response using the edible spacer. SETTING: A university children's hospital in
      Western Australia. SUBJECTS: Two volunteers with moderate asthma. RESULTS:
      Compared with a standard spacer, the edible spacer delivered significantly more
      bronchodilator in droplets of a size likely to enter the respiratory tract. A
      significant bronchodilator response occurred in two out of two subjects when
      salbutamol was inhaled orally via the chocolate spacer. No significant
      bronchodilator response occurred in either subject when the spacer was eaten at
      the end of the study. CONCLUSION: The chocolate spacer used in this study is a
      suitable device to deliver salbutamol by inhalation. However, there may be
      potential drawbacks of weight gain in some patients and meltdown in hot climates.

PMID- 8538550
TI  - Lead poisoning by a mug.

PMID- 8538552
TI  - Supraventricular tachycardia: response to cardioinversion.

PMID- 8538551
TI  - Going bush--helping medical students learn from aboriginal people.
AB  - OBJECTIVE: To help medical students learn about Aboriginal culture and health by
      introducing them to Aboriginal people living in rural and remote areas. SETTING:
      A seven-day field trip to Aboriginal communities and local health services in the
      eastern Goldfields Region of Western Australia. METHODS: Students interviewed
      local Aboriginal people, and representatives of community organisations and
      health service providers, and supplemented this information with their own field
      observations. The field research was used in completing three community health
      projects: one on infant health, another on environmental health, and a third on
      general beliefs of Aboriginal people about health and disease, prevention and
      treatment, and traditional and Western medicine. MAIN OUTCOME MEASURES: Knowledge
      about and attitudes towards Aboriginal people were assessed by anonymous
      questionnaires before and after the field trip. RESULTS: The field trip tripled
      (on average) the number of Aboriginal people with whom the students had ever had
      a conversation. Potentially important increases were seen in the proportion of
      students who could correctly name actions of doctors that Aboriginal people might
      find offensive. Seven of the nine students "strongly agreed" that their attitudes
      to Aboriginal people were more positive as a result of the trip, and the other
      two "agreed". All would recommend such a trip to their colleagues. CONCLUSIONS:
      By visiting Aboriginal communities, medical students can gain important insights
      into Aboriginal health problems and ways in which health services can be made
      more acceptable to Aboriginal people.

PMID- 8538553
TI  - The Walter and Eliza Hall Institute of Medical Research 1965-1995: from basic
      research to clinical triumphs.

PMID- 8538554
TI  - As time goes by: reflections on 40 years of academic medicine and biomedical
      research.
AB  - Professor Firkin of the Department of Medicine at Melbourne's Monash University
      says that, despite considerable advances, many unanswered questions remain in
      modern medicine. The bright medical minds that may answer these questions are
      being lost to the cause because of rigid postgraduate training schemes and
      inadequate remuneration.

PMID- 8538555
TI  - Where the national research dollar goes. Allocation of NHMRC resources to
      clinical categories, 1989-1995. National Health and Medical Research Council of
      Australia.

PMID- 8538556
TI  - The John Curtin School of Medical Research: past achievements and future
      directions.

PMID- 8538557
TI  - Resources down the drain.

PMID- 8538558
TI  - In the tail of the taipan. A personal view of snakebite and serum sickness.

PMID- 8538559
TI  - Snakebite deaths in Australia 1992-1994 and a management update.
AB  - Twelve deaths attributed to snakebite were reported in 1992-1994. Eight of the
      victims were males, and brown snakes (genus Pseudonaja) were involved in six of
      the deaths. Deaths caused by brown snakes were often sudden and unexpected, and
      autopsy findings were usually unremarkable. In no case was prompt effective first
      aid applied. The importance of appropriate first aid is emphasised and an update
      on management presented.

PMID- 8538560
TI  - Psychiatric casualties in the Pacific during World War II: servicemen
      hospitalised in a Brisbane mental hospital.
AB  - World War II created many psychiatric casualties but precise incidences were not
      accurately established. Battle shock was under-reported as some commanding
      officers were reluctant to admit that their men experienced battle stress. The
      objective in triage of any casualties was to retain as many patients in the war
      zone as possible, if further useful service was feasible. This also applied to
      soldiers with stress-related symptoms, who were treated in base hospitals as near
      to an operational zone as possible. The main treating maxims were "immediacy,
      proximity and expectancy", which involved rapid early treatment in the war zone,
      hoping for an early return to duty (which often meant active duty). Only those
      with severe psychiatric illness were sent back to their home country. The medical
      officer had to be sure that the patient had not responded to treatment before
      sending him home. During the war, the terminology used for psychological
      responses to the stress of combat was derived from several classifications in
      textbooks. Psychiatric nomenclature, barely adequate for civilian psychiatry, was
      totally inadequate for military psychiatry during that period. The aim of
      classification was to facilitate data collection rather than to provide
      definitive diagnoses. Psychiatric therapies during World War II were, at least to
      some degree, diagnostically non-specific. Diagnosis varied according to the
      soldier's proximity to the war zone (i.e., less severe diagnoses were given to
      men closer to the frontline, who would be required in battle). In addition, as
      psychiatrists were rarely available, medical officers without relevant (or having
      only limited) specialty training usually diagnosed and treated soldiers with
      psychiatric problems. At the beginning of the war, traumatic psychiatric
      reactions were classified into psychoneurosis, anxiety state and anxiety
      reaction, psychoneurosis mixed, and conversion hysteria. By the end of the war,
      the United States Surgeon General released a revised nomenclature with two new
      diagnostic categories: transient personality reactions to acute and special
      stress; and neurotic-type reactions to routine military stress. It was not until
      the 1950s that formal criteria for the diagnosis of trauma appeared, in the first
      diagnostic and statistical manual (DSM-I) of the American Psychiatric
      Association.

PMID- 8538561
TI  - A gynaecological view of European history.

PMID- 8538562
TI  - The early history of convulsive therapies in Australia.
AB  - The early experience of convulsive therapies in Australia was reported in the
      Medical Journal of Australia from 1935 to 1950. Cardiazol convulsive therapy,
      first used in Australia in 1937, appears to have been widely employed.
      Electroconvulsive therapy, first used here in 1941, rapidly became accepted as a
      mainstream treatment. Early response rates are discussed, as well as Australian
      adaptations of European techniques. Clinicians of the day considered the use of
      these procedures carefully and were circumspect about their future role.

PMID- 8538563
TI  - Iodine nutrition in two Tasmanian cultures.

PMID- 8538564
TI  - Bloodletting: the story of a therapeutic technique.
AB  - Bloodletting has been practised in most cultures for the past two millennia.
      Originally widely applied, it is now only indicated for a small number of
      specific medical conditions. Bloodletting declined in the 19th century at a time
      of revolution in medical thought, and examining its decline illustrates the
      forces that have shaped modern medicine.

PMID- 8538565
TI  - The 1994 eruption of the Rabaul volcano, Papua New Guinea: injuries sustained and
      medical response.
AB  - On 19 September 1994, with little warning, two volcanoes erupted at the Rabaul
      caldera, affecting the heavily populated Gazelle Peninsula, East New Britain
      Province, Papua New Guinea. Local health services were able to deal with the
      disaster without additional external resources. The preparedness of the
      population and their knowledge of safe areas gained from a disaster plan widely
      publicized a decade earlier contributed to the low number of casualties.

PMID- 8538567
TI  - Eastern Europe in transition: the dilemmas of health.
AB  - As the former Iron Curtain countries reconstruct, they must grapple with the
      health problems left by 40 years of public health neglect. Public health expert
      Konrad Jamrozik reports on his observations as a visiting fellow in Krakow,
      Poland, and asks: can they take the best and avoid the worst from the West?

PMID- 8538566
TI  - Paediatric surgery in Cambodia.
AB  - More than half of Cambodia's nine million people are under 17 years of age, but
      there are no certified paediatric surgeons. On a mission sponsored by CARE
      Australia and the International Federation of Surgical Colleges, Paddy A Dewan
      investigated the surgical care of Cambodia's children.

PMID- 8538568
TI  - The Australian Medical Support Force in Rwanda.
AB  - In the aftermath of the Rwandan civil war, Australia's defence forces deployed a
      medical force to support the United Nations Assistance Mission. In this article,
      Wayne Ramsey, Commander of the Australian contingent, Lindsay R Bridgford,
      Officer Commanding Bravo Section, Robert J Lusby, Lt.-Colonel (Surgeon),
      Australian Medical Support Force Hospital, and John H Pearn, Colonel, and
      Director of Intensive Care in the Australian Medical Support Force Hospital,
      describe the Australian effort in the rebuilding of a shattered people and, in
      particular, of Kigali Central Hospital, the country's major medical facility.

PMID- 8538569
TI  - Is Wednesday's child filled with woe? An evidence-based reassessment.

PMID- 8538570
TI  - Is there a "suicide season" in the Northern Territory?

PMID- 8538571
TI  - Stingray envenomation: a suggested new treatment.

PMID- 8538572
TI  - Going up in smoke.

PMID- 8538574
TI  - Measuring resistance to phagocytosis of group A and G streptococci: comparison of
      direct bactericidal assay and flow cytometry.
AB  - M protein is thought to contribute to the ability of non-opsonized group A and
      group G streptococci (GAS and GGS, respectively) to resist phagocytosis by
      polymorphonuclear leukocytes. In previous studies, correlation between M protein
      expression and phagocytosis was determined by incubating these pathogens in human
      blood and comparing colony-forming bacterial counts prior to and after exposure
      to blood (direct bactericidal assay; DBA). Here, we report the application of
      flow cytometry to measure GAS and GGS resistance to phagocytosis. The results of
      the assays were in complete agreement with those from DBAs. Nevertheless, flow
      cytometry was regarded as superior to DBA because of its speed and potential uses
      for quantitative studies. In addition, the use of anti-CD11b monoclonal antibody
      for granulocyte staining guaranteed a non-compromized granulocyte function. The
      optimized protocol for flow cytometry presented here could be utilized to
      directly measure the involvement of individual protein types in bacterial
      resistance to phagocytosis.

PMID- 8538573
TI  - Superantigens and pseudosuperantigens of gram-positive cocci.
AB  - Superantigens use an elaborate and unique mechanism of T lymphocyte stimulation.
      Prototype superantigen are the pyrogenic exotoxins produced by Staphylococcus
      aureus and Streptococcus pyogenes. Many candidate proteins of bacterial, viral
      and protozoal origin have recently been reported to be superantigens. In most
      cases the evidence that these proteins are in fact superantigens is highly
      indirect. In this review the evidence that gram-positive cocci produce
      superantigens other than the pyrogenic exotoxins is critically discussed.
      Evidence in described demonstrating that the epidermolytic toxins of
      Staphylococcus aureus and the pyrogenic exotoxin B and M-proteins of
      Streptococcus pyrogenes are not superantigens. Criteria are described for
      acceptance of a candidate as a superantigen.

PMID- 8538576
TI  - Hemagglutination by Staphylococcus aureus strains responsible for human
      bacteremia or bovine mastitis.
AB  - Although hemagglutination by Staphylococcus aureus has been associated with the
      pathogenesis of bovine mastitis, this trait has not been characterized with
      regard to human disease. In this study, the prevalence of hemagglutination in 100
      strains of S. aureus responsible for bovine mastitis or human bacteremia, was
      characterized. Under optimum conditions hemagglutination was noted in 23% of the
      bovine strains, but only 13% of human strains, leading us to conclude that this
      trait is not a significant virulence determinant in human systemic infection.
      Additional studies indicate the hemagglutinin of S. aureus strains responsible
      for human bacteremia is proteinaceous in character.

PMID- 8538575
TI  - Molecular and immunological characterization of the p83/100 protein of various
      Borrelia burgdorferi sensu lato strains.
AB  - The complete coding regions of the chromosomally encoded p83/100 protein of four
      Borrelia garinii strains and one Borrelia burgdorferi sensu stricto strain have
      been amplified by the polymerase chain reaction (PCR), cloned and sequenced. From
      alignment studies with the deduced amino acid sequences presented here, and five
      other published p83/100 sequences, the most heterologous region of the p83/100
      molecule was identified to be located between amino acid position 390-540. To
      study the structure of this heterogeneous region, and internal fragment of the
      p83/100 genes from 11 additional B. burgdorferi sensu lato strains was amplified
      by PCR. The PCR products were analyzed by DNA sequencing and restriction enzyme
      analysis. These internal p83/100 fragments varied in size and sequence. Cluster
      analysis of internal p83/100 fragments, as well as restriction enzyme analysis,
      revealed three major groups in accordance with grouping into the three species
      causing Lyme disease. Strains within the same species (six B. burgdorferi sensu
      stricto and six B. afzelii strains) showed similar p83/100 partial structures.
      Nevertheless, nine B. garinii strains showed more sequence variations and could
      be further divided into two major subgroups. One group is represented by OspA
      serotype 4 strains, the other more heterogeneous group is represented by OspA
      serotypes 3, 5, 6 and 7 strains. Phenotypic analysis with four p83/100-specific
      monoclonal antibodies revealed four distinct reactivity patterns. Antibody L100
      1B4 recognized a common epitope of B. burgdorferi sensu stricto and B. afzelii.
      Antibodies L100 17D3 and L100 18B4 were reactive with an epitope shared by
      strains of all three species. The broadest reactivity was shown by L100 18B4
      which, in contrast to L100 17D3, additionally recognized the relapsing fever
      borreliae B. turicatae and B. hermsii. L100 8B8 detected a subgroup of the B.
      burgdorferi sensu stricto strains. Since comparison of the p83/100 molecule with
      sequences from protein databases showed similarities with characteristics of
      eukaryotic cell structures, the p83/100 might mimic these structures and may,
      therefore, be involved in the immune escape mechanism of the pathogenic agent of
      Lyme disease.

PMID- 8538577
TI  - Characterization of Vibrio cholerae El Tor cytolysin as an oligomerizing pore
      forming toxin.
AB  - V. cholerae El Tor cytolysin is a secreted, water-soluble protein of M(r) 60,000
      that may be relevant to the pathogenesis of acute diarrhea. In this
      communication, we demonstrate that the toxin binds to and oligomerizes in target
      membranes to form SDS-stable aggregates of M(r) 200,000-250,000 that generate
      small transmembrane pores. Pores formed in erythrocytes were approximately 0.7 nm
      in size, as demonstrated by osmotic protection experiments. Binding was shown to
      occur in a temperature-independent manner preceding the temperature-dependent
      oligomerization step. Pores were also shown to be formed in L929 and HEp-2 cells,
      human fibroblasts and keratinocytes, albeit with highly varying efficacy. At
      neutral pH and in the presence of serum, human fibroblasts were able to repair a
      limited number of lesions. The collective data identify V. cholerae El Tor
      cytolysin as an oligomerizing toxin that damages cells by creating small
      transmembrane pores.

PMID- 8538578
TI  - Antiviral action of interferon-beta on Newcastle disease virus: selectivity to
      the hemagglutinin-neuraminidase gene expression.
AB  - Interferon-beta (IFN-beta) strongly inhibited the expression of the hemagglutinin
      neuraminidase (HN) gene of Newcastle disease virus (NDV), a paramyxovirus, in
      HeLa cells under the conditions where it did not affect the expression of the
      four upstream genes encoding the nucleocapsid protein, phosphoprotein, membrane
      protein and fusion protein. Even the downstream gene, encoding the large protein
      as well as the genome replication, appeared to be less susceptible to IFN-beta
      than the HN gene. This selective action of IFN-beta did not appear to be
      attributable to its well characterized antiviral mechanisms such as acceleration
      of RNA decay and translation inhibition. No similar down-regulation of a
      particular gene expression was found with another paramyxovirus, Sendai virus, or
      with a rhabdovirus, vesicular stomatitis virus, or seems to have been reported
      previously with any negative-strand RNA viruses. This new effect of IFN-beta thus
      suggests gene expression mechanism unique to NDV and may further lead to the
      discovery of a novel biochemical effect of IFN-beta.

PMID- 8538580
TI  - [Adenolymphoma of the salivary glands. The anatomicoclinical, epidemiological and
      therapeutic aspects of 76 cases].
AB  - A series of 76 cases of adenolymphoma (Warthin's tumor) of the salivary glands is
      presented with emphasis on its epidemiological, clinico-pathological and
      therapeutic features; together with the analysis of the clinical records and of
      the epidemiological data, this study has reevaluated the histopathological
      features of the 76 cases of Warthin's tumor on hematoxylin-eosin stained slides.
      On these bases, the authors underline the frequent multifocality and/or
      bilaterality of Warthin's tumor (11.3% of cases), its frequent association with
      tumors of other sites (11.3% of cases), the prevalence in males (M:F ratio =
      24:1) and in adults (mean age: 57 years) of this type of tumor. Furthermore, this
      study confirms the parotid gland as the elective site for Warthin's tumor and the
      possibility to categorize this entity into four different histological types. The
      latter finding should be kept in mind especially when fine needle aspiration
      (FNA) is used as a preoperative diagnostic procedure for Warthin's tumor to avoid
      misleading diagnosis and overtreatment. From the analysis of the results the
      authors underline the need for a complex and multidisciplinary approach to the
      diagnosis of Warthin's tumor in order to allow conservative surgery with
      preservation of the facial nerve.

PMID- 8538581
TI  - [The current therapeutic trends in rhabdomyosarcoma of the cervicofacial area. A
      review of the topic].
AB  - The authors describe the most common clinical characteristics and main parameters
      of classification of rhabdomyosarcoma in the maxillo-facial area. They draw the
      most actual therapeutic iter with particular reference to surgical directions,
      and they examine different prospects of applicability and of prognostic result.

PMID- 8538579
TI  - Comparative cutaneous testing with purified protein derivative and the antigen
      complex A60 in vaccinated subjects and tuberculosis patients.
AB  - Some 840 bacille Calmette-Guerin (BCG)-vaccinated healthy controls and
      tuberculosis patients from two Chinese hospitals were submitted to comparative
      skin tests with purified protein derivative of tuberculin (PPD; as reference) and
      with the antigen complex A60 from Mycobacterium bovis BCG. In a first trial,
      including 581 persons (185 healthy juveniles, 180 healthy adults and 216
      tuberculosis patients), a limited dose of A60 (1 microgram) was used. Performance
      of the A60 test was similar to that of 5 I.U. PPD for controls (cut-off values =
      5 mm induration diameter), but lower than that seen for tuberculosis patients (10
      mm cut-off values). A second survey was conducted on 259 persons (109 recently
      revaccinated healthy persons, considered as tuberculin-negative in the first
      trial, and 150 tuberculosis patients), using a higher dose of A60 (2 micrograms)
      and the same dose of PPD (5 I.U.). Similar results were obtained with the two
      tests in all cases, thus supporting the possibility of PPD replacement by A60 in
      cutaneous testing. The pattern of induration diameter distribution in healthy
      subjects who took part in the first testing round (64% positively rate) was
      displaced to the inactivity side (with a peak at 5 to 9-mm diameter), in
      comparison with the second round (90% positivity rate and peak at 10-14 mm). This
      indicates a progressive fading of cellular immunity reactions after BCG
      vaccination. In tuberculosis patients, no correlation was found among the
      following three parameters: positivity at cutaneous testing (with PPD or A60),
      titer of anti-A60 mycobacterial immunoglobulins in blood (IgG titer higher than
      cut-off line) and presence of mycobacteria in sputum.

PMID- 8538582
TI  - [The role of the basic skeletal system in the stomatognathic apparatus. A
      critical review of the literature].
AB  - The authors make a literature review on the different interpretations of the
      stomatognathic apparatus and try to identify any component of it and to underline
      the importance of the basal skeletal structures (maxilla and mandible). In this
      study the authors examined three female patients affected by different
      pathologies (dysfunctional, malformative, and traumatic) treated at the Maxillo
      Facial Surgery Department of "La Sapienza" University of Rome; in all cases the
      basal skeletal structures were involved with a total functional alteration of the
      stomatognathic apparatus. The primary aim of any maxillo-facial surgical
      treatment is the restoring of skeletal structural harmony with a re-equilibrium
      of all the components of the apparatus. In conclusion the authors confirm the
      importance of the basal skeletal system which is strictly connected to all other
      elements, for the physiologic structural development and functional harmony of
      the stomatognathic apparatus.

PMID- 8538583
TI  - [Brodie's syndrome. A report of 2 atypical cases].
AB  - The aim of the authors is to show the treatment of Brodie's syndrome even in
      atypical cases where this pathology can not offer typical signs but can be
      associated to other skeletal deformities of the face. There are two atypical
      cases of Brodie's syndrome both of them came to our out patient's department.
      They were grown-up (one 20 one 22 years old), one of them with an extreme
      vertical expansion of lower third of the face and with a big transverse expansion
      of the upper maxillary bone, all typical signs of Brodie's syndrome; the other
      patient was with an extreme transverse expansion of the upper maxilla associated
      to a II class and a defect of 11, 12, 21, 22. The first patient was treated with
      orthodontic Tweed technique continued with surgical operation setting out to the
      contraction of the transverse diameter of the upper maxilla, associated to a Le
      Fort I osteotomy and an Epker osteotomy of the jaw. This orthodontic-surgical
      correction, allowed us to achieve a good aesthetic and functional result. The
      second patient was treated with orthodontics followed by surgical correction of
      the excessive transverse expansion of the upper maxilla after a Le Fort I
      osteotomy; a sagittal split of the jaw on Gotte technique was performed to
      correct the III class. We gave the patient a good aesthetic result with the
      restoration of the lost teeth in the upper maxilla, reaching in this way a good
      aesthetic and a well functioning result. We think it's possible to treat patients
      with atypical Brodie's syndrome with orthodontics or surgery in the same way we
      treat Brodie's syndrome and other deformities of the face reaching good aesthetic
      functional results.

PMID- 8538584
TI  - [A new device for the disinfection of handpieces and turbines].
AB  - Dental handpieces are often difficult to disinfect. This is one of the main
      reasons for the considerable risk of cross-infections in dental offices. The aim
      of the present study was the evaluation of the disinfectant property of a recent,
      commercially available, automatic instrument, described as capable to clean,
      disinfect and lubricate dental handpieces. The following experimental evaluations
      were made: 1) antimicrobial activity of the disinfectant (glyoxalaldehyde) used.
      The method described by the European Committee for Standardization was followed.
      Test microorganisms were Pseudomonas aeruginosa and Staphylococcus aureus. 2)
      disinfection of dental handpieces (69 contra-angles and 97 turbines of different
      marks). They were naturally infected using them on patients for 30 minutes at
      least. 3) disinfection of dental handpieces infected with bacterial suspensions
      of Staphylococcus aureus, Streptococcus pyogenes (beta-haemolyticus, group A),
      Candida albicans and Pseudomonas aeruginosa. The results of the first experiment
      showed a strong bactericidal power of the disinfectant with both the tested
      strains, after a contact time of only 1 minute. A great proportion of the dental
      handpieces tested during the second experiment were found disinfected: from 84%
      through 89% out of the various models of turbine handpieces; from 89% through
      100% out of the models of contra-angle handpieces. Even though bacterial
      contamination level was low (about 10(3) microorganisms per handpiece), a
      satisfactory disinfectant ability in natural conditions was found. The results of
      the third experiment were unclear. The tested instrument reduced 10(5)-10(8)
      times the original bacterial count when the gram positive microorganisms
      (Staphylococcus aureus, Streptococcus pyogenes) were used. On the other hand,
      when Pseudomonas aeruginosa and Candida albicans were used, the results were
      different: the bacterial count was reduced 10(6)-10(7) times in some cases, and
      only 10(2) times in other cases. This difference was found in the tests made
      using the same attachment and in those made using various attachments. In
      conclusion, the tested instrument showed, in most cases, a good disinfectant
      property, but the presence of unclear results suggests that some technical
      modifications are required.

PMID- 8538585
TI  - [Oral administration of OK-432 is an effective immunotherapy against colon cancer
      -a study in a murine mesenteric lymphnode metastasis model].
AB  - A simple and highly reproducible mouse colonic cancer model with mesenteric lymph
      node (MLN) metastasis was established by injecting COLON-26 tumor cells into
      lymphatic nodules in the tip of vermiform appendix of BALB/C mice. In this model,
      antitumor effect of orally administered OK-432 was examined. OK-432 was given
      orally at three different periods: before injection of COLON-26 cells (Protocol
      A), early after injection of COLON-26 cells (Protocol-B), and late after
      injection of COLON-26 cells (Protocol-C). As a result, MLN metastasis was
      significantly suppressed and survival rate was significantly improved in every
      protocol as compared to mice without OK-432 administration. Then, in vivo anti
      tumor activities of MLN cells and splenic lymphocytes were evaluated by Winn
      assay. Tumor neutralizing activity against syngenic COLON-26 cells was induced in
      the MLN cells after OK-432 administration and the effector cells were found in
      CD4-positive T lymphocytes because MLN cells treated with anti-L3/T4 and anti-LFA
      plus complement lost their anti-tumor efficacy. In conclusion, oral
      administration of OK-432 appears to be an effective immunotherapy against colonic
      cancer especially in the prevention and the treatment for MLN metastasis.

PMID- 8538586
TI  - [Assessment of disturbance of urinary bladder function after an operation for
      rectal cancer].
AB  - Disturbance of urinary bladder function occurs frequently after operations on
      rectal cancer. Clinical studies of 15 male patients with resected rectal cancers
      revealed a close relationship between the disturbance of urinary bladder function
      and the extent to which the autonomic nerves in the pelvis were disturbed.
      Clinically, transection of the hypogastric nerve did not affect urinary function.
      Branches to the urinary bladder in the pelvic plexus controlled bladder function
      bilaterally. Transection of one side of the pelvic splanchnic nerve (PSN) did not
      affect bladder function. Partial transection of the bilateral PSN strongly
      affected bladder function, but in these cases, compensation by the non-disturbed
      PSN improved urinary bladder function 3 months after the operation. It seems
      possible that the lower-grade branches to the urinary bladder in the PSN may
      control bladder function. Uroflowmetry, amount of residual urine, cystometry, and
      urinary bladder compliance were all useful in assessing disturbance of branches
      to the urinary bladder in the PSN. To assess the grade of severe Clinical cases,
      it proved the most convenient to examine the uroflowmetry and amount of residual
      urine.

PMID- 8538587
TI  - [Studies of liver macrophage function in the intraabdominal infection after
      partial hepatectomy in the rat model].
AB  - The activities of superoxide (O2-), tumor necrosis factor (TNF) and interleukin-1
      (IL-1) of rat liver macrophage (M phi) were studied in the condition of
      intraabdominal infection (E group), hepatectomy (H group) and intraabdominal
      infection following hepatectomy (HE group). In the early stage of E and HE
      groups, O2- production was significantly increased after infection. In the H and
      HE groups, O2- production was significantly increased at 48 hours after
      hepatectomy, probably due to liver regeneration. In every group, the changes of
      TNF activity showed the similar pattern to those of O2- production. In H and E
      groups, the elevation of IL-1 activities was significantly increased. However in
      HE group, the IL-1 level remained low during 72 hours. When the M phi 48 hours
      following hepatectomy was stimulated by lipopolysaccharide (LPS), activities of
      TNF and IL-1 were correlated and reversely correlated with the LPS level,
      respectively. In the excessive stimulation by infection following hepatectomy, IL
      1 activity is significantly suppressed with production of O2- and TNF by M phi
      maintained.

PMID- 8538588
TI  - [The effect of the external biliary diversion on cobalamin functions].
AB  - We studied the effect of the external biliary diversion on cobalamin functions
      clinically and experimentally. Serum cobalamin was rising to 10 ng/ml or more in
      each patient with obstructive jaundice and the diverted bile contained high
      concentrations of cobalamin (10-80 ng/ml). A total volume of diverted cobalamin
      reached to 2-12 micrograms/day after the relief of obstruction and was maintained
      2-8 micrograms/day even after 30 days. In experimental dogs, serum cobalamin
      decreased to 360 +/- 40pg/ml (about 31% decreases) subsequent eight weeks after
      the relief. The cobalamin concentration of liver decreased to 184 +/- 123ng/g
      (19% decreases) after four weeks and to 164 +/- 108ng/g (30% decreases) after
      eight weeks. The concentration of the different cobalamins in the liver showed
      that the proportion of dimethyl benzimidazolyl cobamide coenzyme (DBCC) decreased
      and the proportion of methylcobalamin increased. It is concluded that cobalamin
      (10 micrograms/day at least) should be administered when the diversion continues
      for a long term.

PMID- 8538589
TI  - [Effect of direct current therapy with chemotherapy in 7,12-dimethylbenz[alpha]
      anthracene (DMBA)-induced rat mammary cancer].
AB  - To improve the quality of life of breast cancer patients with local recurrence,
      we investigated the effect of direct current therapy in combination with
      chemotherapy. In this study we chose 3mA of direct current and 1mg/kg of CDDP as
      optimum based upon a prior experimental study. Rats with mammary cancer induced
      by 7,12-dimethylbenz [alpha] anthracene (DMBA) were divided into four groups
      based upon therapeutic methods: direct current therapy alone (Group DC),
      chemotherapy alone (Group CT), direct current therapy with chemotherapy (Group
      DC+CT) and no treatment (control). The percentage of tumor area 6 weeks after
      therapy was 30.8% of the metropeutic size in the Group DC+CT, 46.8% in the Group
      DC, 107% in the Group CT and 267% in the control (Group DC+CT vs the other
      groups: p < 0.05). The response rate in the Group DC+CT (100%) was significantly
      higher than that in the other three groups (chi 2-test, p < 0.05). The platinum
      concentration ratio of both tumor/serum (p < 0.01) and tumor/kidney (p < 0.05) in
      the Group DC+CT was significantly higher than that in the Group CT. We conclude
      that direct current therapy in combination with chemotherapy strongly reduces
      mammary tumor size of rats.

PMID- 8538590
TI  - [A clinicopathological study of angiogenesis in breast cancer].
AB  - To evaluate the clinicopathological significance and the objective methods for
      angiogenesis, we immunohistochemically stained all of the regions around the
      cancer nests with Factor VIII-related antigen staining. We also identified
      microvessels in the many areas all along the border between cancer nests and the
      stroma by 200 x power field. We then examined the relationship between the
      average microvessel count (AC/mm2) and clinicopathological factors and between a
      10-year cumulative survival rate in 109 cases of primary breast cancer from 1971
      to 1979. There were an average of 35 fields counted among all the cases, and AC
      was 39.1 +/- 16.1. AC without blood vessel invasion was 36.4 +/- 15.2, while AC
      with blood vessel invasion was 44.7 +/- 16.6 (p < 0.02). AC without node
      metastasis or with n1 alpha was 37.6 +/- 15.4, while AC with n1 beta or n2 or n3
      was 45.2 +/- 17.4 (p < 0.05). There was no relationship between AC and clinical
      tumor size, histological classification, lymphatic invasion, nuclear grade, and
      histological extension. A 10-year cumulative survival rate in AC (> or = 39) was
      62.4%, while that in AC (< 39) was 82.7% (p < 0.03). Thus AC was considered a
      useful prognostic factor.

PMID- 8538591
TI  - [Calcium metabolism in porcine liver transplantation].
AB  - The influence of warm ischemia on calcium metabolism in liver transplantation
      (LTX) was investigated using temporary portal vein arterialization (PA)
      technique. Group I pigs were added no warm ischemia (n = 6). In group II, donors
      were killed by KCl, and the livers were left in situ for 60 min (n = 6). After
      anastomosing the suprahepatic vena cava, revascularization was carried out
      employing PA. Initial reperfused blood was collected through the infrahepatic
      vena cava. All pigs survived more than 4 days in group I, whereas all died within
      2 days in group II. In group II, Ca2+ levels of initial reperfused blood were
      significantly lower than those of arterial blood. Ca2+ levels of initial
      reperfused blood in group II were significantly lower than those in group I.
      Within 90 min after revascularization, biliary output and biliary calcium content
      and excretion in group I recovered to 30%, 100% and 40% of normal, respectively,
      but in group II only 2 animals could excrete bile. In conclusion, in the liver
      with 60 min warm ischemia, Ca2+ influx occurred immediately after
      revascularization followed by decreased calcium excretion in bile, which
      suggested that accumulation of calcium might be one of the causes of warm
      ischemic injury.

PMID- 8538592
TI  - [Contribution of insulin resistance on intracellular glucose metabolism in
      patients with cancer: preliminary report].

PMID- 8538593
TI  - [Influence of acute aortic dissection, on platelet function second department of
      surgery, department of pharmacy: preliminary report].

PMID- 8538594
TI  - [Dynamic cardiomyoplasty for chronic heart failure induced by femoral
      arteriovenous shunt: preliminary report].

PMID- 8538595
TI  - [Treatment of experimental ascites with retroviral vector producer cells inserted
      with human interleukin-2 gene: preliminary report].

PMID- 8538596
TI  - [Analysis of the distribution of microsatellites of seven motiffs within a cosmid
      of an ordered human chromosome 13 library].

PMID- 8538597
TI  - [Molecular mechanisms of directing biosynthesis of nucleic acids. Theoretical
      study of complementary base pair recognition by DNA polymerases].

PMID- 8538598
TI  - [Multiple alignment of biopolymer sequences, based on the search for
      statistically significant common segments].

PMID- 8538599
TI  - [Electrophoretic study of conformational transitions in poly(A) at acid pHs].

PMID- 8538601
TI  - [Theory of melting of chemically modified DNA containing a cross-link between
      chains].

PMID- 8538600
TI  - [Potential for pseudorotation of deoxyribose within double-helical (C,G)
      oligonucleotides].

PMID- 8538602
TI  - [Dimers of DNA triplexes].

PMID- 8538603
TI  - [A cracked state of the double-helical DNA].

PMID- 8538604
TI  - [Mutant human gamma-interferons with a changed C-terminus and their properties].

PMID- 8538605
TI  - [Comparison of three-dimensional structures of flexible protein molecules].

PMID- 8538606
TI  - [A model system for rapid screening of antiretroviral compounds].

PMID- 8538607
TI  - [Screening of YAC-clones and creation of a contig covering the region of human
      chromosome 13, often deleted in B-cell chronic lymphocytic leukemia].

PMID- 8538608
TI  - [Concentration of proto-oncogenes in hepatocyte nuclei].

PMID- 8538609
TI  - [Multiple drug resistance in yeasts and its effect on stability and karyotype of
      transformants].

PMID- 8538610
TI  - [A new class of repeating elements in the inter-genic spacer in diploid Aegilops
      umbellulata rDNA].

PMID- 8538611
TI  - [Cyclic oligonucleotides. Hybridization properties and ability to cause cleavage
      of RNA by RNAse H].

PMID- 8538612
TI  - [Changes in the conformation of a cofactor in the complex of aspartate
      aminotransferase with D-aspartate].

PMID- 8538613
TI  - [Distribution and phylogenetic analysis of HTLV-I isolates, persisting in the
      Russian Far East].

PMID- 8538614
TI  - [Loop-domain organization of genes in eukaryotic chromosomes].

PMID- 8538615
TI  - [A new method of designing hybrid genes--the homolog recombination method].

PMID- 8538616
TI  - [Analysis of thermostable structural bases of bacilliary secretory
      metalloproteinases based on a model of chimeric enzymes].

PMID- 8538617
TI  - PPAR: a mediator of peroxisome proliferator action.
AB  - Peroxisome proliferators are a diverse group of rodent hepatocarcinogens that
      include hypolipidemic drugs, plasticizers and herbicides. These compounds when
      administered to rats and mice produce a dramatic increase in the size and number
      of hepatic peroxisomes and increase the capacity of the hepatocyte to metabolise
      fatty acids by inducing peroxisomal beta-oxidation enzymes such as acyl CoA
      oxidase. Members of the steroid hormone receptor superfamily of ligand-activated
      transcription factors have been identified that can be activated by peroxisome
      proliferators and are therefore called 'peroxisome proliferator activated
      receptors' (PPAR). There appear to be four PPAR isoforms within vertebrates
      termed alpha, beta, gamma and delta and the alpha isoform appears to be the one
      that is most strongly activated by synthetic peroxisome proliferators such as Wy
      14,643. It has been demonstrated that PPAR alpha forms a heterodimer with the
      retinoid X receptor (RXR) and binds to specific DNA sequences located upstream of
      peroxisome proliferator responsive genes. It is therefore suggested that PPARs
      mediate the pleiotropic effects of peroxisome proliferators including the
      regulation of gene expression and rodent hepatocarcinogenesis. Rodents fed a high
      fat diet develop peroxisome proliferation and many of the enzymes induced by
      peroxisome proliferators are involved in fatty acid metabolism. Furthermore,
      PPARs are activated by a wide range of fatty acids and hypolipidemic drugs, such
      as clofibrate, that lower triglyceride levels in man. Although it remains to be
      determined whether fatty acids and peroxisome proliferators bind directly to any
      PPAR these data suggest that the natural role of PPARs in man is to regulate
      lipid homeostasis. Interestingly, hypolipidaemic drugs fail to elicit peroxisome
      proliferation in human hepatocytes although hypolipidaemic effects are observed
      in patients. A further understanding of the role of PPAR in man will require: (1)
      the identification of additional human PPARs combined with functional analyses
      using these and other nuclear receptors that can antagonise PPAR action; (2) a
      comparison of the expression of these different receptors in human tissues; (3) a
      clearer understanding of how peroxisome proliferators and fatty acids activate
      PPAR; and (4) sequence analysis of the regulatory regions in the human
      counterparts of rodent peroxisome proliferator responsive genes. Together, these
      data will provide an important mechanism-based framework to assess the hazard of
      peroxisome proliferators to humans.

PMID- 8538618
TI  - Receptor-mediated events and the evaluation of the Environmental Protection
      Agency (EPA) of dioxin risks.

PMID- 8538619
TI  - Mechanisms and pathogenesis of thyroid cancer in animals and man.
AB  - The transformation of the normal fully differentiated thyroid follicular cell to
      the rapidly growing undifferentiated anaplastic thyroid carcinoma cell involves a
      number of stages which have been defined morphologically and are now being
      related to various growth pathways and to molecular biological defects. The two
      main factors involved in this transformation are growth stimulation and
      mutagenesis. Growth stimulation alone, through elevated TSH, can lead to the
      development of thyroid tumours, usually benign, and retaining TSH dependency in
      some cases. Mutagens alone, if growth is suppressed, do not produce tumours, the
      combination of mutagens and increased growth is a potent carcinogenic regime. Non
      genotoxic carcinogenesis in the thyroid involves growth, without mutagenesis the
      agent often causes this through affecting one component of thyroid hormone
      synthesis or metabolism, leading to a fall in thyroid hormone levels and a rise
      in TSH. Growth stimulation increases the rate of cell division, and therefore
      increases the chance of a mutation. Continued growth increases the change of
      subsequent events, in particular loss of heterozygosity in a tumour suppressor
      gene. The main oncogenes involved in human thyroid carcinogens are ras in the
      follicular tumour pathway, and ret in the papillary carcinoma pathway. p53 is
      involved in the progression of either papillary or follicular adenoma to an
      undifferentiated carcinoma. In experimental thyroid carcinogenesis, ras is again
      involved, with a link between the mutagenic agent used and the type of ras gene
      showing mutation. Analysis of the involvement of different growth factors and
      oncogenes in thyroid carcinogenesis suggests that genes related to the two
      receptors concerned with normal TSH stimulated growth, TSH receptor and the IGF1
      receptor may be involved in the progression of thyroid tumours of follicular
      pathology. Several tyrosine kinase receptors with unknown ligands or of uncertain
      physiological function are linked to papillary carcinoma. The recent large
      increase in papillary carcinoma of the thyroid in children exposed to fallout
      from the Chernobyl nuclear accident underlines the importance of understanding
      the pathobiology of thyroid neoplasia.

PMID- 8538620
TI  - Mechanistic considerations for the relevance of animal data on thyroid neoplasia
      to human risk assessment.
AB  - There are two basic mechanisms whereby chemicals produce thyroid gland neoplasia
      in rodents. The first involves chemicals that exert a direct carcinogenic effect
      in the thyroid gland and the other involves chemicals which, through a variety of
      mechanisms, disrupt thyroid function and produce thyroid gland neoplasia
      secondary to hormone imbalance. These secondary mechanisms predominantly involve
      effects on thyroid hormone synthesis or peripheral hormone disposition. There are
      important species differences in thyroid gland physiology between rodents and
      humans that may account for a marked species difference in the inherent
      susceptibility for neoplasia to hormone imbalance. Thyroid gland neoplasia,
      secondary to chemically induced hormone imbalance, is mediated by thyroid
      stimulating hormone (TSH) in response to altered thyroid gland function. The
      effect of TSH on cell proliferation and other aspects of thyroid gland function
      is a receptor mediated process and the plasma membrane surface of the follicular
      cell has receptors for TSH and other growth factors. Small organic molecules are
      not known to be direct TSH receptor agonists or antagonists; however, various
      antibodies found in autoimmune disease such as Graves' disease can directly
      stimulate or inhibit the TSH receptor. Certain chemicals can modulate the TSH
      response for autoregulation of follicular cell function and thereby increase or
      decrease the response of the follicular cell to TSH. It is thus important to
      consider mechanisms for the evaluation of potential cancer risks. There would be
      little if any risk for non-genotoxic chemicals that act secondary to hormone
      imbalance at exposure levels that do not disrupt thyroid function. Furthermore,
      the degree of thyroid dysfunction produced by a chemical would present a
      significant toxicological problem before such exposure would increase the risk
      for neoplasia in humans.

PMID- 8538621
TI  - Mechanisms of hormone-mediated carcinogenesis of the ovary in mice.
AB  - Experimental ovarian carcinogenesis has been investigated in inbred and hybrid
      strains of mice and induced by a diversity of mechanisms including X-irradiation,
      oocytotoxic xenobiotic chemicals, ovarian grafting to ectopic or orthotopic
      sites, neonatal thymectomy, mutant genes reducing germ cell populations, and
      aging. The mechanisms are briefly reviewed whereby disruptions in the function of
      graafian follicles results in a spectrum of ovarian proliferative lesions
      including tumors. The findings in mutant mice support the concept of a secondary
      (hormonally-mediated) mechanism of ovarian carcinogenesis in mice associated with
      sterility. Multiple pathogenetic factors that either destroy or diminish the
      numbers of graafian follicles in the ovary result in decreased sex hormone
      secretion (especially estradiol-17 beta) leading to a compensatory over
      production of pituitary gonadotrophins (particularly luteinizing hormone), which
      places the mouse ovary at an increased risk to develop tumors. The intense
      proliferation of ovarian surface epithelium and stromal (interstitial) cells with
      the development of unique tubular adenomas in response to sterility does not
      appear to have a counterpart in the ovaries of women.

PMID- 8538622
TI  - Mechanisms of transcription activation by nuclear receptors: studies on the human
      glucocorticoid receptor tau 1 transactivation domain.
AB  - Nuclear receptors are important signalling molecules that directly mediate the
      effects of hormones, vitamins and xenobiotic compounds at the level of gene
      expression. Several members of this superfamily of proteins have been implicated
      in receptor-dependent carcinogenesis. In this review, we summarise how these
      receptors can function as transcription factors with particular emphasis on the
      mechanism of transcription activation by the human glucocorticoid receptor tau 1
      transactivation domain.

PMID- 8538623
TI  - Protein kinase D (PKD): a novel target for diacylglycerol and phorbol esters.
AB  - A novel serine/threonine protein kinase regulated by phorbol esters and
      diacylglycerol (named PKD) has been identified. PKD contains a cysteine-rich
      repeat sequence homologous to that seen in the regulatory domain of protein
      kinase C (PKC). A bacterially expressed NH2-terminal domain of PKD exhibited high
      affinity phorbol ester binding activity (Kd = 35 nM). Expression of PKD cDNA in
      COS cells conferred increased phorbol ester binding to intact cells. The
      catalytic domain of PKD contains all characteristic sequence motifs of serine
      protein kinases but shows only a low degree of sequence similarity to PKCs. The
      bacterially expressed catalytic domain of PKD efficiently phosphorylated the
      exogenous peptide substrate syntide-2 in serine but did not catalyse significant
      phosphorylation of a variety of other substrates utilised by PKCs and other major
      second messenger regulated kinases. PKD expressed in COS cells showed syntide-2
      kinase activity that was stimulated by phorbol esters in the presence of
      phospholipids. We propose that PKD may be a novel component in the transduction
      of diacylglycerol and phorbol ester signals.

PMID- 8538624
TI  - Protein kinase C and skin tumor promotion.

PMID- 8538625
TI  - Protein serine/threonine phosphatases as binding proteins for okadaic acid.
AB  - Recently, many potent inhibitors of protein serine/threonine phosphatases (PPs)
      have been found. Some of them have proven to be tumor promoters in mouse skin two
      step carcinogenesis and rat liver medium-term tests. Among these inhibitors,
      okadaic acid (OA) selectively inhibits PP2A, and its use has therefore been
      proposed to facilitate analysis of biological roles of this phosphatase. OA shows
      bimodal effects on in vitro transformation and, in addition to such epigenetic
      changes, also induces marked genetic changes. OA treatment for more than 1 week
      flattened NIH 3T3 transformants irreversibly, with loss of the transfected genes.
      It is also known to induce diphtheria toxin-resistant mutations in Chinese
      hamster lung cells and sister chromatid exchanges (SCEs) in Chinese hamster ovary
      cells and human lymphocytes. To analyze roles of protein phosphatases in gene
      stability, we isolated OA-resistant mutants. They were proven to have a mutation
      in the PP2A alpha catalytic subunit, in which cysteine 269 had been substituted
      for glycine; and it was demonstrated that this region interacts with OA. The
      recombinant mutant protein was 4 approximately 9-fold more resistant to OA than
      the wild type. Although the OA resistant mutants of CHO cells expressed high
      levels of P-glycoprotein, inhibition of PP2A itself was suggested to lead to SCE
      induction. However, the number of molecular species of PP which are known to be
      sensitive to OA continues to increase, and we have isolated cDNA for a novel type
      of OA sensitive PP. Our studies indicate that the fact that the roles of PP2A
      cannot be elucidated using only OA is of crucial importance.

PMID- 8538626
TI  - Intercellular communication and carcinogenesis.
AB  - Two types of intercellular communication (humoral and cell contact-mediated) are
      involved in control of cellular function in multicellular organisms, both of them
      mediated by membrane-embedded proteins. Involvement of aberrant humoral
      communication in carcinogenesis has been well documented and genes coding for
      some growth factors and their receptors have been classified as oncogenes. More
      recently, cell contact-mediated communication has been found to have an important
      role in carcinogenesis, and some genes coding for proteins involved in this type
      of communication appear to form a family of tumor-suppressor genes. Both
      homologous (among normal or (pre-)cancerous cells) as well as heterologous
      (between normal and (pre)cancerous cells) communications appear to play important
      roles in cell growth control. Gap junctional intercellular communication (GJIC)
      is the only means by which multicellular organisms can exchange low molecular
      weight signals directly from within one cell to the interior of neighboring
      cells. GJIC is altered by many tumor-promoting agents and in many human and
      rodent tumors. We have recently shown that liver tumor-promoting agents inhibit
      GJIC in the rat liver in vivo. Molecular mechanisms which could lead to aberrant
      GJIC include: (1) mutation of connexin genes; (2) reduced and/or aberrant
      expression of connexin mRNA; (3) aberrant localization of connexin proteins,
      i.e., intracytoplasmic rather than in the cytoplasmic membrane; and (4)
      modulation of connexin functions by other proteins, such as those involved in
      extracellular matrix and cell adhesion. Whilst mutations of the cx 32 gene appear
      to be rare in tumors, cx 37 gene mutations have been reported in a mouse lung
      tumor cell line. Our results suggest that aberrant connexin localization is
      rather common in cancer cells and that possible molecular mechanisms include
      aberrant phosphorylation of connexin proteins and lack of cell adhesion
      molecules. Studies on transfection of connexin genes into tumor cells suggest
      that certain connexin genes (e.g., cx 26, cx 43 and cx 32) act as tumor
      suppressor genes.

PMID- 8538627
TI  - Mechanisms for species differences in receptor-mediated carcinogenesis.
AB  - Species differences resulting from a number of mechanisms are common in receptor
      mediated chemical carcinogenesis. In this review, examples of possible mechanisms
      underlying these differences are discussed, including ligand metabolism, receptor
      polymorphisms, receptor isoforms, receptor levels, and crosstalk between signal
      transduction pathways. In addition, a number of other mechanisms also are likely
      to be important. The developmental state of the animal will determine the
      expression of receptors in different tissues. The regulatory pathways for cell
      proliferation and cell death and cell cycle check point controls can vary among
      species and tissues. Adaptation or potentiation of responses during chronic
      exposures to chemicals can greatly influence species differences. The mechanisms
      of adaptive processes are poorly understood but probably highly important for
      chronic toxicities such as cancer. Finally, different species may have different
      stem cell populations that are the targets for neoplastic transformation, and
      this will influence receptor-mediated carcinogenic responses. The implications of
      species differences in receptor-mediated responses for risk assessment are
      discussed.

PMID- 8538628
TI  - The c-erbB transmembrane growth factor receptors as serum biomarkers in human
      cancer studies.
AB  - Over-expression of the transmembrane growth factor receptors encoded by the c
      erbB oncogenes contributes to cellular transformation in model systems and is
      found to be a frequent occurrence in human tumors. Over-expression of these
      receptors results in accumulation of the extra-cellular domain in the extra
      cellular supernatant in vitro and in elevated levels of the extra-cellular domain
      in serum in vivo in animal models. Similarly, elevated levels of the extra
      cellular domain of these receptors have been detected in the serum of individuals
      with various cancers, including of the breast, ovary, prostate, stomach,
      pancreas, colon, liver, and lung. In some cases, elevated serum levels have been
      detectable prior to the time of clinical diagnosis of disease. Thus, the serum
      levels of the extra-cellular domains of the c-erbB transmembrane growth factor
      receptors may be useful biomarkers of carcinogenesis in human studies.

PMID- 8538629
TI  - Genetic toxicity in relation to receptor-mediated carcinogenesis.
AB  - There is growing agreement on the types and number of assays required to assess
      the ability of a chemical to mutate or to affect in a heritable manner the
      expressional integrity of DNA. This usually involves measurement of the ability
      of a chemical to induce chromosomal aberrations or gene mutations in cultured
      cells, coupled to confirmation of genetic toxicity in rodents. The results of
      such assays, coupled to assessment of the chemical structure of the agent for
      sites of actual or potential electrophilicity, provide a major and primary input
      to estimation of whether a rodent carcinogen is operating by a genotoxic or a non
      genotoxic mechanism. The extent and sites of carcinogenesis also contribute to
      this decision. In cases where the mechanism of action of a carcinogen is to be
      studied in detail, additional assessments of genetic toxicity can be made in the
      species/gender/tissue subject to carcinogenesis. Suitable assays include
      measurements of DNA adducts (e.g., 32P post-labelling), assessment of DNA damage
      using, for example, the single-cell gel electrophoresis (Comet) assay, or the
      determination of transgenic mutation frequencies in appropriate rodent model
      systems. The genetic toxicity of o-anisidine, methyl clophenipate, etoposide and
      taxol are discussed to illustrate these concepts. The present need is for high
      quality genetic toxicity data to be derived and integrated with other relevant
      toxicological data on a new carcinogen in order to provide an informed estimate
      its most likely mechanisms of carcinogenic action.

PMID- 8538630
TI  - Receptor-mediated mechanisms in carcinogenesis: an overview.

PMID- 8538631
TI  - Membrane bound receptor tyrosine kinases and chemical carcinogenesis.

PMID- 8538632
TI  - The aetiology and pathogenesis of human breast cancer.
AB  - Whilst investigators have clearly shown that non-hereditary factors dominate the
      aetiology of human breast cancer, they have failed to identify quantitatively
      important causes, and prospects for prevention remain indeed limited. However,
      progress in epidemiological and basic research has taken place during the last
      few years. Current evidence suggests that breast cancer may be affected by the
      intra-uterine environment, that exposures during adolescence are particularly
      important, and that pregnancy has a dual effect on breast cancer risk: an early
      increase followed by long-term protection. Great variation exists in the
      structural development of the breast ductal system already in the newborn--and by
      inference in utero--and a pregnancy induces permanent structural changes in the
      mammary gland. We suggest that these observations fit into an aetiological model
      with the following key components: (1) breast cancer risk depends on the number
      of cells at risk, the susceptibility of individual cells to malignant
      transformation, and on the degree of cellular proliferation, notably cells which
      can act as founders of breast cancer; (2) the number of target cells is
      determined by the hormonal environment mainly early in life, perhaps already in
      utero; (3) in adult life, hormones which are non-genotoxic, increase breast
      cancer risk by increasing selective cell proliferation and thus number of target
      cells and the risk of retention of spontaneous somatic mutations; (4) while a
      pregnancy stimulates the growth of already malignant cells or cells close to
      malignant transformation (and thereby entails a short-term risk increase) the
      dominating long-term protection occurs due to permanent structural changes,
      terminal differentiation and perhaps decreased cell proliferation and carcinogen
      binding in combination.

PMID- 8538633
TI  - The role of receptors in multistage carcinogenesis.
AB  - The principal characteristic of neoplasia is its inherited alteration of genetic
      expression. The regulation of gene expression may be altered both by mutational
      events and by environmental mediators. During carcinogenesis the permanent
      alterations in genetic expression resulting from mutations occur primarily during
      the final stage of progression when biological malignancy becomes evident. During
      the preceding reversible stage of promotion, alteration and genetic expression
      are the result of the chronic stimulation of an altered (initiated) cell
      responding to the environmental mediator or promoting agent. A major mechanism of
      this effect occurs by receptors exhibiting specificity for the mediator and for
      their interaction with the genome. Withdrawal of the promoting agent prior to the
      genetic alterations characteristic of the stage of progression leads to a
      reversal of the effects of the promoting agent and the death by apoptosis of most
      cells in the stage of promotion. Carcinogenesis mediated by the chronic ligand
      (promoting agent)-receptor interaction increases the probability of the
      development of the stage of progression; thus alteration or prevention of the
      stage of promotion by removal of the promoting agent or inhibition of its action
      remains the best opportunity for cancer prevention. Application of the reversible
      promoting agent-receptor interaction to specific environmental circumstances
      where such plays a major role can lead to a more rational risk estimation of
      promoting agents for the human population.

PMID- 8538634
TI  - Animal models for breast cancer.
AB  - Rodent mammary tumors induced by chemical carcinogens have proven to be very
      useful in the genetic analysis of initiation, promotion and progression of
      mammary carcinogenesis. We are studying rat mammary carcinomas induced by the
      chemical carcinogen, N-nitroso-N-methylurea. The earliest genetic event observed
      in the mammary gland is the activation of Ha-ras oncogenes, which is followed by
      promotion of the initiated cells by hormones involved in puberty. Preferential
      amplification of the mutated Ha-ras allele, of PRAD-1 and IGF2, loss of
      expression of the mitogenic growth factor gene, MK, and mutation in the tumor
      suppressor gene, p53, are seen in the mammary tumors during tumor progression.

PMID- 8538635
TI  - Tissue-specific actions of antioestrogens.

PMID- 8538636
TI  - Risk assessment issues in breast cancer.
AB  - Breast cancer is the most common malignancy affecting women, and its incidence
      has been increasing in many countries. The aetiology of breast cancer is poorly
      understood, so there is concern as to which factors in our environment or
      lifestyle are responsible for the increase. There is a need for reliable risk
      assessment, which involves the steps of hazard identification, hazard evaluation,
      exposure evaluation and risk estimation. Short-term laboratory tests and long
      term tests in animals are useful for priority-setting, but quantitative human
      risk assessment should preferably involve observations of humans. Epidemiological
      studies vary in the degree of reliance that can be placed on their results. The
      main types of epidemiological investigation are illustrated by recent examples
      from the literature on breast cancer. Careful judgement is required in assessing
      whether any association between a factor and a disease is likely to be causal.
      The injectable contraceptive, depot medroxyprogesterone acetate (DMPA, 'Depo
      Provera'), has been controversial because it caused malignant mammary tumours in
      beagle dogs. Two recent case-control studies found no overall association between
      DMPA and the risk of breast cancer in women. There was some evidence of increased
      risk in certain sub-groups of women, which could be interpreted with more
      confidence if there were a better understanding of the biology of human breast
      cancer. Nevertheless, the results do not support the prediction from beagle
      experiments that DMPA might increase the overall risk of breast cancer.

PMID- 8538637
TI  - Hormones and cancer in humans.
AB  - Hormones play a major role in the aetiology of several of the commonest cancers
      worldwide, including cancers of the endometrium, breast and ovary in women and
      cancer of the prostate in men. It is likely that the main mechanisms by which
      hormones affect cancer risk are by controlling the rate of cell division, the
      differentiation of cells and the number of susceptible cells. Hormones have very
      marked effects on cell division in the endometrium; oestrogens stimulate mitosis
      whereas progestins oppose this effect. The risk for endometrial cancer increases
      with late menopause, oestrogen replacement therapy and obesity, and decreases
      with parity and oral contraceptive use; thus risk increases in proportion to the
      duration of exposure to oestrogens unopposed by progestins, probably because
      unopposed oestrogens stimulate endometrial cell division. The effects of hormones
      on breast epithelial cell division in non-pregnant women are much less clear-cut
      than their effects on the endometrium, but both oestrogens and progestins appear
      to stimulate mitosis. Breast cancer risk increases with early menarche, late
      menopause and oestrogen replacement therapy, probably due to increased exposure
      of the breasts to oestrogen and/or progesterone. Early first pregnancy and
      multiparity reduce the risk for breast cancer, probably due to the hormonally
      induced differentiation of breast cells and the corresponding reduction in the
      number of susceptible cells. Hormones do not have marked direct effects on the
      epithelial cells covering the ovaries, but hormones stimulate ovulation which is
      followed by cell division during repair of the epithelium. Risk for ovarian
      cancer increases with late menopause and decreases with parity and oral
      contraceptive use, suggesting that the lifetime number of ovulations may be a
      determinant of risk. For all three of these cancers risk changes within a few
      years of changes in exposure to sex hormones and some of the changes in risk
      persist for many years, indicating that hormones can affect both early and late
      stages of carcinogenesis. Understanding of the role of sex hormones in the
      aetiology of prostate cancer and of some rarer cancers is less complete.

PMID- 8538638
TI  - Role of receptors in human and rodent hepatocarcinogenesis.
AB  - The liver is a major target organ in rodent carcinogenicity assays. Amongst the
      agents that are effective in producing rodent liver tumours are many chemicals
      which are not mutagenic, but are believed to mediate their effects by promoting
      the clonal outgrowth of initiated cells. Some of these chemicals, such as dibenzo
      p-dioxins and certain PCBs, have been demonstrated to interact with specific
      cellular receptors and receptor binding appears crucial for their tumourigenic
      activity. Enzyme-altered foci in rat liver may serve as a sensitive means to
      estimate the promoting activity of these agents in rodents. Mechanistic
      considerations are of relevance when extrapolating these data from rodents to
      humans.

PMID- 8538639
TI  - Apoptosis and multistage carcinogenesis in rat liver.
AB  - Apoptosis is a type of active cell death. It is involved in the homeostasis of
      cell number in tissues and is controlled by the growth regulatory network in the
      organism. It is also involved in the active removal of damaged cells. We have
      studied the role of apoptosis in cancer pre-stages and overt cancer in vivo,
      using rat liver as our main model system. Quantitative determination of apoptosis
      in histological specimens revealed that the rate of apoptosis tends to increase
      from normal to (pre)neoplastic to malignant cells. Thereby active cell death
      largely counterbalances the increasing replicative activity in developing
      malignancy. Tumor promoters shift the balance in favor of cell replication,
      whereas promoter withdrawal, fasting or TGF-beta 1 favor apoptosis (anti
      promotion). Preneoplastic cells are more susceptible than normal liver cells to
      stimulation of both cell replication or cell death. Consequentially
      (pre)neoplastic tissue may preferentially grow or die during the appropriate
      treatment. Regimens that favor apoptosis and lower cell replication are shown to
      result in the elimination of preneoplastic cell clones from the liver (anti
      initiation) and to reduce the cancer risk of the animal.

PMID- 8538640
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits DNA synthesis in rat primary
      hepatocytes.
AB  - Treatment of Sprague-Dawley (SD) rats with a dosing regimen of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) maintaining a steady-state liver concentration
      of 150 ng/g results in enhanced hepatocyte proliferation in the periportal
      region, but reduced proliferation in the remainder of the hepatic lobule (Fox et
      al. (1993) Cancer Res., 53, 2265-2271). Here, we report an initial
      characterization of the actions of TCDD on hepatocyte proliferation by monitoring
      DNA synthesis in primary hepatocytes isolated from SD rats. TCDD caused a dose
      dependent inhibition (EC50 = 10 pM) of DNA synthesis in primary hepatocytes
      isolated from either male or female SD rats in the presence or absence of known
      hepatocyte mitogens (epidermal growth factor, hepatocyte growth factor, and
      transforming growth factor alpha). No change in DNA synthesis was observed at
      TCDD concentrations less than 1 pM. Initial characterization of the EGF response
      system in these cells revealed that TCDD did not alter the specific binding of
      EGF, or the levels of EGF receptor protein measured in intact cells or cell
      lysates. TCDD-dependent inhibition of DNA synthesis occurred independently of the
      suppression observed with transforming growth factor-beta 1. Estradiol did not
      alter DNA synthesis in the presence or absence of TCDD. Taken together, these
      findings indicate that TCDD suppresses DNA synthesis via a novel pathway that is
      non-responsive to estradiol, independent of TGF-beta, and does not involve a
      decreased ability of hepatocytes to recognize (bind) EGF, a prototype mitogen.

PMID- 8538641
TI  - A novel DNA N-glycosylase activity of E. coli T4 endonuclease V that excises 4,6
      diamino-5-formamidopyrimidine from DNA, a UV-radiation- and hydroxyl radical
      induced product of adenine.
AB  - We report on a novel activity of T4 endonuclease V. This enzyme is well known to
      be specific for the excision of pyrimidine dimers from UV-irradiated DNA. In this
      work, we show that T4 endonuclease V excises 4,6-diamino-5-formamidopyrimidine
      from DNA. 4,6-Diamino-5-formamidopyrimidine is formed as a product of adenine in
      DNA upon action of hydroxyl radicals and upon UV-irradiation. DNA substrates were
      prepared by UV-or gamma-irradiation of DNA in aqueous solution. DNA substrates
      were incubated either with active T4 endonuclease V or with heat-inactivated T4
      endonuclease V or without the enzyme. After incubation, DNA was precipitated and
      supernatant fractions were separated. Supernatant fractions after derivatization,
      and pellets after hydrolysis and derivatization were analyzed by gas
      chromatography/isotope-dilution mass spectrometry. The results provide evidence
      for the excision of 4,6-diamino-5-formamidopyrimidine by T4 endonuclease V from
      both gamma-and UV-irradiated DNA. Kinetics of excision were also determined.
      Fifteen other pyrimidine- and purine-derived base lesions that were identified in
      DNA samples were not substrates for this enzyme. It was concluded that, in
      addition to its well known activity for pyrimidine photodimers, T4 endonuclease V
      possesses an N-glycosylase activity for a major UV-radiation- and hydroxyl
      radical-induced monomeric product in DNA.

PMID- 8538642
TI  - Isolation of a cDNA encoding a UV-damaged DNA binding factor defective in
      xeroderma pigmentosum group E cells.
AB  - XPE binding factor (XPE-BF) is deficient in a subset of patients from xeroderma
      pigmentosum complementation group E. Binding activity copurifies with a 125 kDa
      polypeptide (p125) that binds to DNA damaged by ultraviolet (UV) radiation and
      many other agents. We isolated cDNA encoding a polypeptide with a predicted amino
      acid sequence that matched the sequences of eleven tryptic peptides derived from
      digestion of XPE-BF purified from human placenta. In vitro transcription and
      translation of the cDNA yielded a polypeptide of 125 kDa that bound specifically
      to UV-damaged DNA. Therefore the cDNA encodes either all or the major component
      of XPE-BF.

PMID- 8538643
TI  - Thymidine kinase deficient cells with decreased TTP pools are hypersensitive to
      DNA alkylating agents.
AB  - The effect of mutational loss of thymidine kinase (TK) on the sensitivity to
      alkylating agents was investigated in promyelocytic, HL-60, and T-lymphoblastoid,
      Molt-3, human leukemia cell lines. Although both cell lines exhibited approx. 1%
      residual TK activity, only HL-60 TK deficient cells had a decreased intracellular
      TTP pool, i.e., 20% of that of the wild-type. When treated with N-methyl-N'
      nitronitrosoguanidine or ethyl methanesulfonate, HL-60 TK deficient cells showed
      significantly increased killing and mutation frequencies at the hypoxanthine
      guanine phosphoribosyl transferase (HGPRT) locus relative than did wild-type.
      Pretreatment of cells with O6-benzylguanine, an inhibitor of O6-alkylguanine-DNA
      alkyltransferase, partially abolished those differences. Molt-3 wild-type and TK
      deficient cells had similar cell survivals and HGPRT mutation frequencies
      following treatment with alkylating agents. These results indicate that TK
      deficiency, only when a concomitant decrease of TTP pool is detected, plays a
      pivotal role in the sensitivity to the cytotoxic and mutagenic effects of
      alkylating agents.

PMID- 8538644
TI  - Repair and processing of DNA damage: a summary of recent progress.

PMID- 8538645
TI  - Overexpression of the natural recO sequence and its effects on DNA repair of
      Escherichia coli.
AB  - The recO gene is required for the RecF pathway of recombination and the repair of
      DNA daughter-strand gaps in Escherichia coli. In this work, the structural
      portion of recO was synthesized by the polymerase chain reaction (PCR) and cloned
      onto expression vectors at their Nco1 fusion cloning site, to eliminate the
      presence of mRNA leader sequence. While the plasmid carrying a Ptac promoter
      failed to overproduce RecO, the plasmid carrying a T7O10 promoter overproduced
      RecO in large quantity, indicating that the natural recO may be overexpressed. An
      increase of intracellular RecO, which may be due to the increased recO gene
      copies or to the induction of RecO synthesis, increased the UV resistance of
      recA, recF, and ssb cells, but did not increase the UV resistance of uvrB, uvrB
      recF, uvrB recA and uvrB ssb cells. We suggest that an increase of intracellular
      RecO may allow some recombination-deficient cells to perform more excision
      repair, thus increasing the survival. The possible causes for RecO overproduction
      on excision repair, and for the differential expression of recO by the Ptac and
      T7 promoter plasmids are discussed.

PMID- 8538646
TI  - The in vitro more efficiently repaired cisplatin adduct cis-Pt.GG is in vivo a
      more mutagenic lesion than the relative slowly repaired cis-Pt.GCG adduct.
AB  - The toxic effect and the mutagenicity of two differentially repaired site
      specific cis-diamminedichloroplatinum(II) (cis-DDP) lesions were investigated.
      Detailed analysis of the UvrABC-dependent repair of the two lesions in vitro
      showed a more efficient repair of the cis-Pt.GG adduct compared to that of the
      cis-Pt.GCG adduct (Visse et al., 1994). Furthermore, previously, a dependency of
      cis-DDP mutagenesis on UvrA and UvrB, but not on UvrC was found (Brouwer et al.,
      1988). To possibly relate survival and mutagenesis to repair, plasmids containing
      the same site-specific cis-DDP lesions as those that were used in the detailed
      repair studies were transformed into Escherichia coli. The results indicate that
      both lesions are very efficiently bypassed in vivo. Mutation analysis was
      performed using a denaturing gradient gel electrophoresis technique, which allows
      identification of mutations without previous selection. Although the cis-Pt.GG
      adduct is in vitro more efficiently repaired than the cis-Pt.GCG adduct, it
      appeared to be more mutagenic. We present a model in which this result is related
      to the previously observed dependency of the mutagenicity of cis-DDP lesions on
      the Uvr A and B proteins.

PMID- 8538647
TI  - Identification of a 116 kDa protein able to bind 1,3-bis(2-chloroethyl)-1
      nitrosourea-damaged DNA as poly(ADP-ribose) polymerase.
AB  - SKI-1 is a 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-resistant glioma cell line
      and SK-MG-1 is a BCNU-sensitive glioma cell line. Both cell lines do not express
      O6-methylguanine-DNA methyl transferase (MGMT) and exhibit comparable levels of 3
      methyladenine DNA glycosylase. In order to detect DNA binding proteins involved
      in alternative DNA repair mechanisms of BCNU damage, we performed Southwestern
      analysis using a DNA probe damaged with BCNU and nuclear protein extracts from
      SKI-1 and SK-MG-1 cell lines. Both cell lines express a protein of M(r) 116,000
      that is able to bind to BCNU-damaged DNA with higher specificity than to
      undamaged DNA. This protein was identified as poly(ADP-ribose) polymerase (PARP).
      Using glioma extracts depleted of PARP or using antibody to block the DNA binding
      domain of PARP no other protein binding to BCNU-treated probe was observed.
      Addition of methoxyamine, an inhibitor of DNA strand breaks, led to a significant
      reduction of PARP binding to BCNU-treated DNA. BCNU treatment of both glioma cell
      lines led to reduced nicotinamide adenine dinucleotide levels, indicating
      activation of PARP. Thus, the recognition and binding of PARP to BCNU-induced DNA
      nicks with concomitant PARP activation may be important processes that are
      involved in the initial stage of DNA repair of BCNU lesions in glial cells.

PMID- 8538648
TI  - Radiation induced DNA damage and damage repair in three human tumour cell lines.
AB  - Three human tumour cell lines (HX142, RT112 and MGH-U1) with different
      radiosensitivities were tested for differences in the rate and/or extent of DNA
      unwinding in alkali as well as for differences in the induction of DNA double
      strand breaks by means of the pulsed field gel electrophoresis, after X
      irradiation. Unlike that which has been found using the non-denaturing filter
      elution technique (NDE, McMillan et al., 1990), no differences in initial DNA
      damage (the extent of alkaline unwinding and the induction of double strand
      breaks) were found for the three cell lines. These data suggest that rather than
      a different number of DNA lesions per Da per Gy between these cell lines,
      structural differences in chromatin structure (related to radiosensitivity) might
      impair the detectability of lesions in some assays like the NDE. The nature of
      such structure differences remains unclear. However, the differences did not
      affect alkaline unwinding profiles, as all three cell lines showed identical
      rates of DNA unwinding after exposure to X-rays. Furthermore, the three cell
      lines did not show significant differences in the kinetics of DNA strand break
      rejoining nor in the amounts of damage remaining after 24 h repair. The results
      obtained in this study, together with other findings, suggest that the three cell
      lines may differ in their 'presentation' of DNA damage.

PMID- 8538649
TI  - Constitutive increase of RecA protein: its influence on pyrimidine dimer excision
      and survival of UV-irradiated Escherichia coli.
AB  - Transformation of E. coli with the plasmid pRA containing recA gene increased the
      constitutive level of RecA protein 50-67 fold. This slightly inhibited pyrimidine
      dimer excision and reduced cell survival in three investigated, UV-irradiated E.
      coli strains. Our data support the view that RecA protein prematurely present at
      a high level may mask the dimers. The masking subsequently reduces the dimer
      excision and switches off the inducing signal.

PMID- 8538650
TI  - Comparison of the rate of excision of major UV photoproducts in the strands of
      the human HPRT gene of normal and xeroderma pigmentosum variant cells.
AB  - Xeroderma pigmentosum (XP) variant patients are genetically predisposed to
      sunlight-induced skin cancer. Fibroblasts from such patients are extremely
      sensitive to mutations induced by UV radiation, and the spectrum of mutations
      induced in their hypoxanthine phosphoribosyltransferase (HPRT) gene differs
      significantly from that seen in normal cells. To determine if this UV
      hypermutability reflects abnormally slow excision repair of cyclobutane
      pyrimidine dimers (CPD) or 6-4 pyrimidine-pyrimidones (6-4s) in that gene, we
      synchronized XP variant and normal fibroblasts, irradiated them in early G1
      phase, 12 or more hours prior to the scheduled onset of S phase, harvested them
      immediately or after allowing various times for repair, and analyzed the DNA for
      photoproducts in the HPRT gene, using quantitative Southern blotting. To incise
      the DNA at CPD, we used T4 endonuclease V; to incise at 6-4s, we first used
      photolyase and UV365nm to reverse CPD and then UvrABC excinuclease. Excision of
      CPD was rapid, preferential, and strand-specific, but there was no significant
      difference in rate between the two kinds of cells. The half life was 4 h in the
      transcribed strand of the gene and 6.5 h in the nontranscribed strand. For
      excision of CPD in the genome overall, this value is 12 h. Excision of 6-4s from
      either strand of the HPRT gene was extremely rapid and preferential in both kinds
      of cells, with a half life of approximately 30 min. The results indicate that the
      UV hypermutability of the XP variant cells cannot be caused by slower rates of
      repair of CPD and/or 6-4s in the target gene for mutagenesis.

PMID- 8538651
TI  - The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in
      yeast.
AB  - Ixr1 is a yeast HMG-domain protein which binds the major DNA adducts of the
      antitumor drug cisplatin. Previous work demonstrated that Saccharomyces
      cerevisiae cells lacking the IXR1 gene were two-fold less sensitive to cisplatin
      treatment than wild-type cells, and the present investigation reveals a six-fold
      difference in yeast having a different background. The possibility that the lower
      cytotoxicity of cisplatin in the ixr1 strain is the result of enhanced repair was
      investigated in rad1, rad2, rad4, rad6, rad9, rad10, rad14 and rad52 backgrounds.
      In three of the excision repair mutants, rad2, rad4 and rad14, the differential
      sensitivity caused by removing the Ixr1 protein was nearly abolished. This result
      demonstrates that the greater cisplatin resistance in the ixr1 strain is most
      likely a consequence of excision repair, supporting the theory that Ixr1 and
      other HMG-domain proteins can block repair of the major cisplatin-DNA adducts in
      vivo. The differential sensitivity of wild-type cells and those lacking Ixr1
      persisted in the rad1 and rad10 strains, however, indicating that these two
      proteins act at a stage in the excision repair pathway where damage recognition
      is less critical. A model is proposed to account for these results, which is
      strongly supported recently identified functional roles for the rad excision
      repair gene products. A rad52 mutant was more sensitive to cisplatin than the
      RAD52 parental strain, which reveals that Rad52, a double-strand break repair
      protein, repairs cisplatin-DNA adducts, probably interstrand cross-links. A rad52
      ixr1 strain was less sensitive to cisplatin than the rad52 IXR1 strain,
      consistent with Ixr1 not blocking repair of cisplatin adducts removed by Rad52
      rad6 strains behaved similarly, except they were both substantially more
      sensitive to cisplatin. Interruption of the RAD9 gene, which is involved in DNA
      damage-induced cell cycle arrest, had no affect on cisplatin cytotoxicity.

PMID- 8538652
TI  - Identification of a damaged-DNA binding domain of the XPA protein.
AB  - The XPA (xeroderma pigmentosum group A) protein is a zinc metalloprotein
      consisting of 273 amino acids which binds preferentially to UV- or chemical
      carcinogen-damaged DNA, suggesting that it is involved in the recognition of
      several types of DNA damage during nucleotide excision repair processes. Here we
      identify a DNA binding domain of the XPA protein. The region of the XPA protein
      responsible for preferential binding to DNA damaged by UV or cis-diammine
      dichloroplatinum(II) (cisplatin) is contained within a truncated derivative of
      the XPA protein, MF122, consisting of 122 amino acids and containing a C4 type
      zinc finger motif. CD (circular dichroism) measurements of the MF122 protein
      showed that it has a helix-rich secondary structure, suggesting that it is a
      discretely folded, functional mini-domain. The MF122 protein should be useful for
      structural investigation of the XPA protein and of its interaction with damaged
      DNA.

PMID- 8538653
TI  - Disruption of DNA-PK in Ku80 mutant xrs-6 and the implications in DNA double
      strand break repair.
AB  - The Chinese hamster ovary (CHO) mutant cell line xrs-6C is highly sensitive to
      radiation and is deficient in DNA double-strand break (DSB) repair. The repair
      defect of xrs-6C is complemented by the human DSB repair gene designated as
      XRCC5. This gene was recently identified as Ku80, which encodes the human
      autoantigen protein Ku p80. Ku80 protein forms heterodimer with the Ku70 subunit
      to form a complex that possesses a DNA end-binding activity. Ku70/Ku80
      heterodimer can recruit the catalytic p350 subunit of the DNA-dependent protein
      kinase. It is demonstrated here that, while the Ku70 mRNA expression is normal in
      the xrs-6C mutant, Ku70 protein is undetectable. However, introduction of human
      Ku80 gene into the mutant lead to increased expression of Ku70 protein and
      restored Ku70 binding to DNA ends, suggesting that mutation of the Ku80 gene
      affected the formation of Ku70/Ku80 dimers and the stability of the Ku70 protein.
      We also demonstrated that, although p350 protein expression in the mutants was
      unaffected, the capacity of p350 to bind to DNA ends was impaired in the mutants.
      After introduction of the human Ku80 into the mutant, the association of p350
      with DNA end was restored, accompanied by recovery in cell survival and DNA
      double-strand break repair. The results in this report show that mutation of the
      Ku80 gene disrupts formation of the Ku70/Ku80 dimer and compromises the ability
      of Ku protein to recruit the DNA-PK p350 subunit to DNA double-strand breaks,
      causing a dysfunction of DNA DSB repair in the cell.

PMID- 8538654
TI  - Normal mutation frequencies of somatic cells in patients receiving growth hormone
      therapy.
AB  - The number of reported cases of malignancy developing in growth hormone (GH)
      users worldwide has increased to more than 40. However, the causal relationship
      between GH administration and the occurrence of malignancies is still uncertain.
      We investigated somatic cell mutation frequencies (Mfs) or variant frequency (Vf)
      at three gene loci in patients with pituitary dwarfism receiving GH therapy to
      clarify the genetic effect of GH. Eighty-eight patients receiving GH therapy for
      at least 3 months and 42 age-matched healthy controls were studied. Mfs at
      hypoxanthineguanine phosphoribosyltransferase (HPRT) and T-cell receptor (TCR)
      loci in GH users were not significantly higher than in the controls. Although a
      few patients seemed to have a slightly increased Vf at the glycophorin A (GPA)
      locus, the difference was not statistically significant. In addition, there was
      no tendency for the Mfs (Vf) at these loci to increase with the duration of the
      GH therapy. These data seem to exclude the possibility that GH induces genetic
      instability in patients with pituitary dwarfism who are receiving GH therapy.

PMID- 8538655
TI  - Blink reflex recovery curves in blepharospasm, torticollis spasmodica, and
      hemifacial spasm.
AB  - R1 and R2 blink reflex responses to single and paired stimuli were investigated
      in 23 control subjects, 21 patients with blepharospasm (BSP), 20 patients with
      torticollis spasmodica (TS), and 23 with hemifacial spasm (HFS). For paired
      stimuli, we compared measurements of area and peak responses at two and three
      times R2 threshold. R1 and R2 indices were calculated as the average of the
      recovery values at 0.5-, 0.3-, and 0.21-s interstimulus intervals to test
      individual patients. Peak amplitude measurements at three times R2 threshold were
      optimal. The R2 index was abnormal in 67% of BSP patients, 37% of TS patients,
      and 50% of HFS patients on the affected side and 20% on the unaffected side. A
      normal R2 index in one third of patients with BSP may indicate that different
      pathophysiological mechanisms are involved in this type of focal dystonia.

PMID- 8538656
TI  - Decline of muscle fiber conduction velocity during short-term high-dose
      methylprednisolone therapy.

PMID- 8538657
TI  - Limited plasticity of human muscle.

PMID- 8538658
TI  - Isolated inferior calcaneal neuropathy.

PMID- 8538659
TI  - Neuromuscular disorders in systemic malignancy and its treatment.

PMID- 8538660
TI  - Simultaneous electromyography and manometry of the anal sphincters in
      parkinsonian patients: technical considerations.

PMID- 8538661
TI  - Lingual neuropathy after a dental procedure.

PMID- 8538662
TI  - Bilateral proximal sciatic neuropathy caused by a fall.

PMID- 8538663
TI  - Myasthenia gravis presenting as uncontrollable flatus and urinary/fecal
      incontinence.

PMID- 8538664
TI  - Tomaculous neuropathy: a clinical and electrophysiological study in patients with
      and without 1.5-Mb deletions in chromosome 17p11.2.
AB  - Tomaculous neuropathy is the descriptive term for the "sausagelike" swellings of
      myelin characteristic of hereditary neuropathy with liability to pressure palsies
      (HNPP). A 1.5-Mb deletion in chromosome 17p11.2 is present in the majority but
      not all cases of HNPP. We reviewed the clinical and electrophysiological features
      of 18 patients with tomaculous neuropathy and compared these features between
      patients with and without the typical large deletion. Patients presented with a
      variety of pressure-induced nerve palsies and brachial plexopathies. Two patients
      presented with generalized symmetric sensorimotor polyneuropathies. Four patients
      were older than their respective probands but were as yet asymptomatic. Nerve
      conduction studies demonstrated prolonged distal latencies out of proportion to
      slowing of conduction velocities, suggesting a distally accentuated myelinopathy.
      DNA analysis revealed the 1.5-Mb deletion in all the familial cases and in 3 of
      the sporadic patients. The clinical and electrophysiological features were
      similar between patients with and without the 1.5-Mb deletion in chromosome
      17p11.2.

PMID- 8538666
TI  - Inclusion body myositis: investigation of the mumps virus hypothesis by
      polymerase chain reaction.
AB  - Inclusion body myositis (IBM) is a distinctive form of chronic inflammatory
      myopathy characterized pathologically by the finding of rimmed vacuoles and 15
      18nm microtubular filamentous inclusions in muscle fiber nuclei and cytoplasm.
      The observation that these filaments resembled nucleocapsids of the paramyxovirus
      group and showed immunoreactivity with mumps virus (MV) antibodies has led to a
      long-standing postulate that IBM may be a "slow" mumps infection. We searched for
      the presence of MV RNA in 34 muscle biopsies (17 frozen and 17 paraffin-embedded)
      from 18 patients with IBM and 43 control biopsies (mainly from patients with
      other forms of inflammatory myopathy) using a polymerase chain reaction (PCR).
      The MV PCR was shown to be sensitive and specific for MV strains (including J-L)
      and the integrity of muscle RNA extracts was confirmed by PCR detection of
      constitutive Ableson tyrosine kinase mRNA. MV RNA was not found in any biopsy
      from the IBM group nor any of the control cases. Our results therefore do not
      support the mumps hypothesis for IBM.

PMID- 8538665
TI  - Single-fiber electromyography in diabetic peripheral polyneuropathy.
AB  - In this study we examined the value of single-fiber electromyography (SFEMG) in
      assessing the degree of reinnervation in diabetic patients with clinical
      neuropathy. Relationships between reinnervation and the degree of metabolic
      control, and/or duration of diabetes were examined. Thirty-six insulin-dependent
      diabetics and 54 non-insulin-dependent diabetics underwent SFEMG examination of
      the tibialis anterior muscle, as well as conventional nerve conduction studies of
      the upper and lower limbs. All patients examined exhibited some abnormality of
      SFEMG even in the presence of normal nerve conduction studies found in 18% of
      patients. In diabetic patients, the jitter in the tibialis anterior muscle
      correlated positively with glycosylated hemoglobin; whereas lower limb nerve
      conduction studies did not correlate with this measure of diabetic control. These
      data suggest that SFEMG is a sensitive measure of nerve function and
      reinnervation and that it may reflect the dynamic changes in metabolic status in
      diabetic patients.

PMID- 8538667
TI  - Electrophysiological evaluation of spinal reflexes during epidural anesthesia in
      an experimental model.
AB  - We assessed the effects of epidural anesthesia with bupivacaine in the rat by
      serial recordings of spinal reflexes. The H wave from plantar muscles after
      electrical stimulation of the sciatic nerve evaluates a large nerve fiber spinal
      reflex arch. The extensor reflex response recorded from quadriceps muscle after
      stimulation of the contralateral tibial nerve assesses a reflex arch with small
      fiber afferents. After epidural injection of 0.2 mL of bupivacaine (0.25%, 0.5%,
      and 1.0% solutions) at the L5-L6 vertebral space, nociceptive, H, and extensor
      reflex responses were abolished within 1-3 min. Duration of complete blockade
      lasted 20-80 min, increasing with the anesthetic concentration, and complete
      recovery occurred after an additional period of 30-40 min. The responses
      recovered to amplitudes similar to preanesthesia controls, indicating that there
      was no damage to the nervous system. This study shows that electrophysiological
      recording and quantitation of nerve reflex responses is a useful and accurate
      method to evaluate the efficacy of local anesthetic agents.

PMID- 8538668
TI  - Ischemic reperfusion causes lipid peroxidation and fiber degeneration.
AB  - Although the neuropathology of ischemic fiber degeneration (IFD) is relatively
      well known, its pathogenesis is poorly understood. One putative mechanism of IFD
      is oxidative stress, causing a breakdown of the blood-nerve barrier (BNB) and
      lipid peroxidation. We evaluated the effect of ischemic reperfusion of rat
      sciatic-tibial nerve seeking biochemical and pathologic evidence of BNB
      disruption and lipid peroxidation. Ischemia, caused by the ligation of the
      supplying arteries to sciatic-tibial nerve, was maintained for 3 h, followed by
      reperfusion. Reperfusion resulted in an increase in nerve lipid hydroperoxides,
      greatest at 3 h, followed by a gradual decline over the next month. Nerve edema
      and IFD consistently became more severe with reperfusion, indicating that
      oxidative stress impairs the BNB (edema) and causes IFD. Reduced reperfusion was
      greatest over distal sciatic nerve and midtibial nerve at day 7. The most
      ischemic segment (midtibial), of nonreperfused ischemic nerves (duration 3 h),
      underwent both edema and IFD that was as pronounced as those of other segments
      after reperfusion, and underwent a smaller increase with reperfusion, suggesting
      that ischemia alone can also cause IFD and edema. The type of fiber degeneration
      was that of axonal degeneration.

PMID- 8538669
TI  - A useful electrophysiologic parameter for diagnosis of carpal tunnel syndrome.
AB  - In 43 patients (50 hands) with clinical manifestations of mild-moderate carpal
      tunnel syndrome (CTS) and 36 healthy volunteers (40 hands), orthodromic sensory
      nerve conduction velocity (SNCV) was measured with surface electrodes in the
      median nerve between the third digit and palm and between the palm and wrist.
      These figures were used to calculate the ratio of distal to proximal conduction
      (distoproximal ratio). All 90 hands were also subjected to other nerve conduction
      studies used for diagnosis of CTS. All control hands presented distoproximal
      ratios < 1.0 reflecting higher conduction rates in the proximal segment. In
      contrast, 49 of 50 CTS hands (98%) presented reversed ratios (> 1.0) indicating
      compromised proximal conduction. The sensitivity of this test was significantly
      greater than that of other methods evaluated, including comparative studies and
      segmental study of the palm-wrist portion of the median nerve. Segmental study of
      median SNCV with calculation of the distoproximal ratio is a sensitive technique
      for diagnosis of CTS in patients with normal findings in standard nerve
      conduction studies.

PMID- 8538670
TI  - On the nature of endogenous antiexcitatory factors in the cerebrospinal fluid of
      patients with demyelinating neurological disease.
AB  - The cerebrospinal fluid (CSF) of patients with demyelinating neurological
      disease, such as Guillain-Barre syndrome or multiple sclerosis, contains factors
      that inhibit the excitatory Na+ current. Such antiexcitatory factors are
      occasionally also detectable in CSF from patients with other neurological
      diseases but were absent from an artificial CSF containing all major CSF
      constituents (electrolytes, amino acids, vitamins, metabolites, albumin). In an
      attempt to characterize these factors, unphysiological pCa or pH values were
      excluded by the application of the Ca2+ chelator EGTA and the use of buffers.
      Heating the CSF for 10 min to 95 degrees C or digesting it with proteases did not
      destroy the antiexcitatory potency. Fractionation of the CSF contents according
      to molecular weight showed that the factors have a molecular weight < 3 kD. This
      excludes proteins, such as antibodies or cytokines, as candidates. Small peptides
      are known to be resistant to some proteases and heating.

PMID- 8538671
TI  - The influence of the reference electrode on CMAP configuration: leg nerve
      observations and an alternative reference site.
AB  - Peroneal and tibial compound motor action potentials (CMAP) recorded using the
      standard belly-tendon montage have different configurations. The peroneal CMAP is
      a smooth dome shape, while the tibial CMAP has a slow-rising initial component
      followed by a higher amplitude negative peak. To evaluate possible causes of
      these differences we investigated the individual activity recordable at the belly
      and tendon electrodes by using a referential montage with the opposite foot as
      the reference. This type recording shows that the peroneal belly site produces
      most of the nerve CMAP, whereas the tendon site generates most of the high tibial
      CMAP. Some features and technical problems of referential CMAP recording using an
      opposite limb reference are shown. An alternative method using an ipsilateral
      distal leg reference site is described. A montage which separately records the
      activity at the belly or tendon electrodes may provide new insight into
      mechanisms of commonly observed nerve conduction phenomena.

PMID- 8538672
TI  - Porcine malignant hyperthermia: genotype and contractile threshold of immature
      muscles.
AB  - We investigated whether malignant hyperthermia (MH)-related contractile
      abnormalities, such as lowered contractile threshold, were expressed in MH
      susceptible (MHS) immature muscles and myotubes. Muscles from neonatal piglets
      homozygous for Arg615 (normal) or for Cys615 (MHS) ryanodine receptor alleles,
      and heterozygotes were used. Intact cell bundles from piglet muscles generally
      were similar in contractile properties to adult muscles of the same genotype.
      Thresholds for K contractures in normal, heterozygous, and MHS piglet muscles (40
      mmol/L, 25 mmol/L and 15 mmol/L K+, respectively) differed significantly.
      Cultured myotubes were subjected to a series of square pulses of varying
      strengths (-50 to +50 mV) and durations (25-300 ms) using whole cell patch-clamp
      techniques. Threshold for contraction differed significantly among the three
      genotypes, for example, with 300 msec pulses thresholds were -6.9 +/- 0.9, -12.4
      +/- 1.6, and -22.6 +/- 2.6 mV for normal, heterozygous and MHS myotubes,
      respectively. Thus a significantly lower than normal threshold for contraction
      was expressed in MHS and heterozygous piglet muscles and myotubes. Further, these
      developmentally immature preparations are likely to express other differences
      characteristic of adult MHS muscles, and thus provide suitable preparations for
      clinically relevant studies of MH-related cellular abnormalities.

PMID- 8538673
TI  - Longitudinal studies of the duplication form of Charcot-Marie-Tooth
      polyneuropathy.
AB  - This study presents a longitudinal comparison of motor nerve conduction
      velocities (MCVs) in patients with Charcot-Marie-Tooth type 1A with proven
      duplication of a segment of chromosome 17p11.2p12. Results were compared for 8
      CMT1A duplication patients from one family whose MCV measurements were taken 22
      years apart (1967 and 1989). Measurements from a total of seven median motor and
      five peroneal motor MCVs were compared. Median MCVs showed a slight reduction
      that averaged 2.2 m/s, and peroneal MCVs showed an average decrease of 3.0 m/s.
      In addition, mild objective increase in limb weakness was seen in only 1 of 8
      patients and subjective symptoms of gradual worsening of leg strength were noted
      in half the patients over the same period. In this study of a small group of
      CMT1A patients with proven segmental duplication of chromosome 17p11.2p12, the
      motor conduction velocities and clinical motor exam did not change significantly
      over 22 years.

PMID- 8538674
TI  - A transgenic mouse model of the slow-channel syndrome.
AB  - To investigate the effect of acetylcholine receptor (AChR) mutations on
      neuromuscular transmission and to develop a model for the human neuromuscular
      disease, the slow-channel syndrome, we generated transgenic mice with abnormal
      AChRs using a delta subunit with a mutation in the ion channel domain. In three
      transgenic lines, nerve-evoked end-plate currents and spontaneous miniature end
      plate currents (MEPCs) had prolonged decay phases and MEPC amplitudes were
      reduced by 33%. Single nerve stimuli elicited repetitive compound muscle action
      potentials in vivo. Transgenic mice were abnormally sensitive to the
      neuromuscular blocker, curare. These observations demonstrate that we can
      predictably alter AChR function, synaptic responses, and muscle fiber excitation
      in vivo by overexpressing subunits containing well-defined mutations. Furthermore
      these data support the hypothesis that the electrophysiological findings in the
      neuromuscular disorder, the slow-channel syndrome, are due to mutant AChRs.

PMID- 8538675
TI  - Intrauterine onset of a mononeuropathy: peroneal neuropathy in a newborn with
      electromyographic findings at age one day compatible with prenatal onset.
AB  - Mononeuropathies are unusual at birth, and electromyographic (EMG) definition the
      first day of life has not been reported previously. Although neonatal
      mononeuropathies may be related to obstetric complications, prenatal mechanisms
      also merit consideration. We report an infant, born with a peroneal neuropathy,
      whose EMG was performed 18 h after birth. An isolated peroneal nerve lesion with
      lack of compound muscle action potential and the presence of fibrillation
      potentials, confined to the tibialis anterior muscle, suggested a primary
      intrauterine mechanism for this mononeuropathy. Because of an infant's small
      size, the temporal profile used in adults for appearance of EMG signs of
      wallerian degeneration may not apply. Inaccurate conclusions may result if the
      EMG standards for timing adult nerve injury are applied to newborns. To our
      knowledge, previous published cases of neonatal mononeuropathies have not
      included babies whose first EMG was performed before age 4 days. Therefore, an
      EMG study shortly after birth needed to be accomplished if strong support for the
      hypothesis of a prenatal onset were to be generated. Our findings are compatible
      with an intrauterine onset of this baby's peroneal neuropathy.

PMID- 8538676
TI  - Brachial plexopathy secondary to mycotic subclavian-axillary artery aneurysm.

PMID- 8538678
TI  - A composite nerve graft system: extracted rat peripheral nerve injected with
      cultured Schwann cells.

PMID- 8538677
TI  - Ubiquitin expression in acute steroid myopathy with loss of myosin thick
      filaments.

PMID- 8538679
TI  - Analysis of the 170-kDa lectin gene promoter of Entamoeba histolytica.
AB  - The promoter region driving the gene for the 170-kDa heavy subunit of the
      Entamoeba histolytica galactose-inhibitable lectin was analysed by transient
      transfection using the chloramphenicol acetyltransferase gene as reporter. S1
      mapping confirmed our previous notion that the promoter is located within a 1.35
      kb intergenic sequence preceding the structural lectin gene. Transcripts derived
      from the chloramphenicol acetyltransferase gene of transfected trophozoites were
      found to be polyadenylated and the transcriptional start mapped to a position
      similar to that of the wild-type lectin gene. By deletion analysis the entire
      promoter was restricted to a fragment covering about 550 bp upstream from the
      start of transcription. On the other hand, residual promoter activity required a
      sequence of about 140 bp only, encompassing a newly identified CCAAT-box like
      element around position -100, as well as the amebic specific TATA-box. This 140
      bp fragment as well as a stretch of 15 bp, which is located some 100 nt further
      upstream, were found to be conserved within the 5' noncoding region of a second
      E. histolytica lectin gene. Point-mutation analyses indicated that the 15-bp
      fragment, the likely CCAAT-box, as well as the TATA-box are required for full
      promoter activity.

PMID- 8538680
TI  - Sequences with high propensity to form G-quartet structures in kinetoplast DNA
      from Phytomonas serpens.
AB  - Naturally occurring sequences containing repetitive guanine motifs have the
      potential to form tetraplex DNA. Phytomonas serpens minicircle DNA shows some
      regions where one strand is composed mainly of G and T (GT regions). These
      regions contain several stretches of contiguous guanines. An oligonucleotide was
      constructed with the sequence corresponding to one of these regions (Phyto-GT).
      It was demonstrated by native gel electrophoresis and methylation protection that
      Phyto-GT forms tetramolecular (G4), bimolecular (G'2) and unimolecular (G4')
      structures stabilized through G-quartets. Tetraplex DNA formation by this
      sequence could have biological relevance as it can be formed in physiological
      conditions and GT regions comprise approximately one-third of P. serpens and
      Crithidia oncopelti minicircles.

PMID- 8538682
TI  - Processing of the Plasmodium chabaudi chabaudi AS merozoite surface protein 1 in
      vivo and in vitro.
AB  - Processing of the Plasmodium merozoite surface protein 1 (MSP-1) has been
      described for parasites maintained under in vitro conditions. We have now
      demonstrated, using CBA/Ca mice infected with Plasmodium chabaudi chabaudi AS,
      that MSP-1 processing also occurs in vivo. The major proteolytic cleavage sites
      and a processing scheme were deduced from N-terminal amino-acid sequences of the
      MSP-1 breakdown products. Comparison of MSP-1 processing in P. falciparum and
      P.c. chabaudi indicates a degree of conservation and in two cases the position of
      protease cleavage appears identical. Significant amounts of MSP-1 polypeptides
      are found in plasma during schizogony. Various aspects of MSP-1 processing
      including immunological and physiological reactions in the host during the
      critical period of schizogony can now be examined in vivo.

PMID- 8538681
TI  - Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene isolation
      and expression and characterization of the enzyme.
AB  - The gene encoding the bifunctional dihydrofolate reductase (DHFR) and thymidylate
      synthase (TS) of Trypanosoma brucei brucei has been isolated and expressed in
      Escherichia coli, and the enzyme has been purified and characterized. The coding
      sequence of the DHFR-TS is 1581 nt, encoding a 527-amino-acid protein of 58,505
      Da. The gene was expressed under control of the trc promoter in pKK233-2. The
      resulting expression plasmid conferred trimethoprim resistance to E. coli DH5
      alpha and complemented the TS deficiency in chi 2913recA cells indicating the
      presence of active DHFR and TS. DHFR-TS was purified by methotrexate-Sepharose
      chromatography. In addition to the full-length enzyme, the purified enzyme
      contained 31 and 31.5-kDa forms of the enzyme that cross-reacted with anti-L.
      major DHFR-TS antibodies; one was truncated at the N- and C termini, and the
      other at only the C terminus. Despite the presence of sufficient TS for
      complementation, TS activity was not detectable in the crude extract or in the
      final purified enzyme preparation. Although the majority of the enzyme appears to
      be full length, it is possible that the TS domain has been degraded by one of
      more residues, which would inactivate the ability to synthesize thymidylate.
      Kinetic analysis of DHFR yielded kcat and Km values similar to those of related
      enzymes. The T. brucei DHFR has Ki values for antimicrobial antifolates
      pyrimethamine and trimethoprim which are significantly lower than the closely
      related T. cruzi or L. major DHFRs or than human DHFR.

PMID- 8538684
TI  - Cloning and characterization of a putative calcium-transporting ATPase gene from
      Schistosoma mansoni.
AB  - Complementary DNA was isolated, encoding a putative Ca(2+)-transport ATPase
      (SMA1) of the human parasitic trematode Schistosoma mansoni. The cDNA was
      isolated by a nested polymerase chain reaction based strategy. The
      oligonucleotides used were designed on the basis of conserved amino-acid regions
      found in P-type ATPases. The complete nucleotide sequence was determined. The
      primary structure and topology of the enzyme were deduced. SMA1 has 1022 amino
      acids and a predicted molecular mass of 113 kDa. This protein is 67% identical
      and phylogenetically related to several sarco/endoplasmic reticulum Ca(2+)
      ATPases but lacks the phospholamban-binding domain that exists in the SERCA
      isoforms 1 and 2. The membrane topology predicted for SMA1 is characteristic of
      the P-type ATPases, showing two major cytoplasmic loops and ten conserved
      hydrophobic segments. Sequences and residues that are important for the function
      of the SER Ca(2+)-ATPase, such as the high-affinity Ca(2+)-binding sites, the
      putative fluorescein isothiocyanate binding site, the 5'-(p
      fluorosulfonyl)benzoyladenosine binding site and the aspartyl phosphorylation
      site, are conserved in SMA1, suggesting that the cloned gene is a Ca(2+)
      transport ATPase of the SERCA family. In addition, three PCR products were cloned
      which share homology with another SER Ca(2+)-ATPase, with the yeast secretory
      pathway Ca(2+)-ATPase PMR1 and its mammalian homologue, and with the alpha
      subunit of a Na+,K(+)-ATPase.

PMID- 8538683
TI  - Isoprenylation of proteins in the protozoan Giardia lamblia.
AB  - We report the ability of Giardia lamblia to modify several of its cellular
      proteins by isoprenylation. Trophozoites cultured in the presence of
      [3H]mevalonate synthesized radiolabeled proteins of approx. 50 and 21-26 kDa.
      Chemical analysis indicated that farnesyl and geranylgeranyl isoprenoids
      comprised the majority of the radiolabel covalently associated with trophozoite
      proteins. In addition, antibodies to human p21ras immunoprecipitated mevalonate
      labelled species of approx. 21 kDa. Inhibitors of several enzymatic steps of the
      mevalonate pathway dramatically affected Giardia metabolism. Protein
      isoprenylation and cell growth were blocked by compactin and mevinolin,
      competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme in
      isoprenoid biosynthesis. In the presence of these inhibitors, Giardia growth was
      restored by the addition of mevalonate to the culture medium. In contrast, cell
      growth was blocked irreversibly by inhibitors of subsequent steps in the protein
      isoprenylation pathway. Trophozoite growth inhibition by limonene, perillic acid,
      perillyl alcohol and N-acetyl-S-farnesyl-L-cysteine was not reversed after the
      addition of mevalonate, dolichol, ubiquinone or cholesterol to the medium. These
      observations constitute the first description of protein isoprenylation in any
      protozoan and indicate that this post-translational modification is an important
      step in the regulation of the growth of this primitive eukaryote.

PMID- 8538685
TI  - A role for second messengers in the control of activation-associated modification
      of the surface of Trichinella spiralis infective larvae.
AB  - The involvement of second messengers in the control of activation-induced changes
      to the surface of Trichinella spiralis infective larvae was investigated using
      membrane-permeant photo-activatable 'caged' compounds to alter intracellular
      levels of inositol trisphosphate (IP3), calcium ions (Ca2+) and cyclic AMP
      (cAMP). Activation of larvae by incubation in culture medium containing trypsin
      and bile was followed by the loss of the surface coat labelled with the
      fluorescent PKH26 lipid probe and this correlated with the reciprocal acquisition
      of surface lipophilicity detected using the fluorescent lipid probe octadecanoyl
      aminofluorescein (AF18). Optimal surface coat shedding and AF18 insertion was
      also achieved following photolysis of caged mediators liberating IP3, Ca2+ or
      cAMP within the parasite. Chelation of Ca2+, however, abolished the effects of
      larval activation. Nevertheless, addition of cAMP (but not IP3) to Ca(2+)
      depleted larvae overcame this inhibition and restored AF18 insertion to levels
      achieved by activated parasites. Therefore, the existence of a linear second
      messenger pathway involving the sequential release of IP3, Ca2+ and then cAMP is
      likely.

PMID- 8538686
TI  - Selection of diversity at putative glycosylation sites in the immunodominant
      merozoite/piroplasm surface antigen of Theileria parasites.
AB  - The immunodominant merozoite/piroplasm surface antigen of Theileria parasites has
      potential as a diagnostic reagent and as a component of a sub-unit vaccine. This
      molecule is known to be antigenically diverse, and it is important to determine
      the nature and extent of this heterogeneity. In the present study nucleotide
      sequences, representing alleles of the gene (Tams1) encoding this molecule in
      Theileria annulata were compared to each other and to sequences of homologous
      genes in Theileria sergenti, Theileria buffeli and Theileria parva. This analysis
      revealed that a region of the polypeptide which contains putative N-linked
      glycosylation sites is particularly diverse and, in analogy to retroviral
      systems, may indicate selection of variable glycosylation sites or amino acid
      epitopes to evade the bovine immune response. This conclusion was also made from
      the results of a phylogenetic analysis which compared the variable region of the
      genes with a second region, which appeared to show no bias for diversity or
      functional constraint. The results indicated that the variable sequence encoding
      putative glycosylation sites has diverged, both within and between Theileria
      species, at a much faster rate than the rest of the molecule. Southern blot
      analysis of T. annulata populations from within a single geographical region
      detected six possible variant Tams1 alleles. However, a correlation between
      restriction-fragment-length polymorphism (RFLP) patterns detected by the Tams1-1
      gene probe and geographical location could not be made. In addition, although a
      high prevalence of one particular RFLP was found, this is unlikely to be the
      result of a clonal population structure, as we present evidence for significant
      parasite genotypic variability within a single endemic region.

PMID- 8538687
TI  - A Plasmodium falciparum protein kinase with two unusually large kinase inserts.
AB  - A protein kinase gene (PfPK1) has been isolated from the human parasite
      Plasmodium falciparum by using a mixed oligonucleotide pool which corresponds to
      a highly conserved region of serine/threonine protein kinases. The gene, which
      contains one intron, encodes a protein with a predicted length of 909 amino
      acids. The predicted protein contains all the conserved sequences characteristic
      of a protein kinase catalytic domain. These sequences are discontinuous, however,
      since they are separated by two large kinase inserts with 178 and 330 amino acids
      in size. Specific antisera were raised against recombinant fragments of the
      protein and a PfPK1-specific peptide. Using one of these antibodies, a functional
      protein kinase was precipitated from malarial lysates and this kinase recognized
      casein as an exogenous substrate. PfPK1 was expressed in a stage-specific fashion
      and also had a stage-specific cellular localization. During the intraerythrocytic
      life cycle, PfPK1 shifts from the parasite cytosol to the parasite membrane
      fraction. An unusual feature of PfPK1 is its electrophoretic mobility on SDS
      PAGE. Whereas the predicted protein size is about 100 kDa, the apparent size is
      about 70 kDa. There are no indications for RNA processing and we could exclude
      proteolytic processing as an explanation.

PMID- 8538688
TI  - Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon
      vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16
      protein produced in yeast.
AB  - Pfs16 is a sexual stage/sporozoite-specific antigen of Plasmodium falciparum and
      is a potential candidate for a sporozoite-neutralizing vaccine. To obtain more
      information on the function of Pfs16 and to investigate its role during
      transmission and hepatocyte invasion, immunization experiments were performed
      with both a Pfs16-specific recombinant vaccinia virus and virus-like particles
      produced in yeast composed of the hepatitis B surface antigen (HBsAg) and antigen
      Pfs16 fused to HBsAg. Upon transformation of yeast cells, harbouring a genomic
      copy of the HBsAg gene, with a plasmid carrying the fusion gene Pfs16-HBsAg
      (Pfs16-S) virus-like hybrid particles composed of HBsAg and Pfs16-S were formed
      of a size similar to those present in human sera after infection with the
      hepatitis B virus. Cells infected with recombinant Pfs16 vaccinia virus
      synthesized a polypeptide of approx. 16 kDa that reacted with a Pfs16-specific
      polyclonal antibody. Animals vaccinated with the yeast hybrid particles and/or
      recombinant vaccinia virus both produced Pfs16-specific antibodies. These
      antibodies showed no transmission-blocking activity, but they efficiently
      diminished or abolished in vitro invasion of sporozoites into human hepatoma
      cells (HepG2-A16) and primary human hepatocytes.

PMID- 8538689
TI  - Sexual-stage-specific RNA expression of a new Plasmodium falciparum gene detected
      by in situ hybridisation.
AB  - A gene, Pf77, transcribed in the sexual stages of Plasmodium falciparum was
      isolated from a genomic expression library with a polyclonal antibody raised to
      gametocyte proteins. The entire coding region was obtained from a series of
      overlapping genomic and cDNA clones (from gametocyte RNA). A single open reading
      frame is present with no introns and no tandem repeat sequences. A Pf77 probe
      hybridised to a single transcript present in RNA prepared from purified
      gametocytes and could not be detected in RNA prepared from asexual blood stages.
      In situ hybridisation studies confirmed that the expression of Pf77 mRNA is
      sexual-stage-specific and in addition, showed that Pf77 mRNA is present only in
      female gametocytes during the vertebrate stages of the parasite's development.

PMID- 8538690
TI  - Extensive polymorphism at the Gp63 locus in field isolates of Leishmania
      peruviana.
AB  - Genetic diversity within and between tandemly arrayed copies of the Gp63 gene
      occurs in laboratory isolates of Leishmania spp., but the extent to which this
      represents natural genetic diversity has not been assessed. Here, the Gp63 locus
      is examined in 58 fresh isolates of L. peruviana, and clones derived from them,
      collected throughout the Peruvian Andes. Extensive polymorphism is observed, both
      in size of Gp63 containing chromosomes, and for restriction-fragment-length
      polymorphisms (RFLPs) at the Gp63 locus. All clones within an isolate are
      identical, including those with two distinct Gp63-hybridising chromosomal-sized
      pulsed-field gel electrophoresis (PFGE) bands, consistent with diploidy but with
      size differences in homologous chromosomes. For RFLP analysis, three enzymes were
      selected to cut within the coding region (PstI), in the intergenic region (SalI)
      and outside (EcoRI) the Gp63 gene cluster. PstI gave identical banding patterns
      across all isolates/clones. For EcoRI and SalI, all clones within an isolate were
      identical, but isolates were polymorphic for fragments at 13 (2-30 kb) and 8 (2.6
      8.8 kb) different molecular mass locations generating 19 and 16 distinct RFLP
      patterns or genotypes for each enzyme, respectively. EcoRI restriction patterns,
      analysed by PFGE, were consistent with the presence of two clusters of Gp63 genes
      on each homologous chromosome, one contained within EcoRI fragments large enough
      to carry from 3 to 10 copies of the Gp63 gene, the second on fragments which
      could carry 1 or 2 copies of the gene. SalI patterns indicated variable
      restriction sites within clusters, but not within every intergenic region. A
      hierarchical analysis of variance of allele frequencies, expressed in terms of
      Wright's F-statistic, indicated significant barriers to gene flow at all levels,
      valleys within regions (north/south), villages within valleys, and individuals
      within villages. This extreme polymorphism at the Gp63 locus of L. peruviana
      demonstrates the great potential for generation of genetic diversity in parasite
      populations.

PMID- 8538691
TI  - Differentiation of a culture-adapted mutant bloodstream form of Trypanosoma
      brucei into the procyclic form results in growth arrest of the cells.
AB  - The bloodstream forms of Trypanosoma brucei monomorphic strain 427 serially
      passaged in rats can differentiate in vitro equally well in HMI-9, HMI-10, SDM-79
      or Cunningham's medium into the insect (procyclic) forms by a simple temperature
      shift from 37 to 26 degrees C in the presence of citrate and cis-aconitate. The
      procyclic forms thus generated can also continue to multiply at 26 degrees C
      without replacing the culture medium. The same strain of T. brucei pre-adapted to
      grow as bloodstream forms in HMI-10 medium at 37 degrees C is also capable of
      differentiating showing a similar rate of variant surface glycoprotein (VSG)
      disappearance and appearance of phosphoenolpyruvate carboxykinase (PEPCK) under
      the same experimental conditions. However, appearance of both procyclin mRNA and
      procyclin protein is much delayed and the resulting procyclic forms cannot
      multiply. The culture-adapted bloodstream forms are capable of infecting rats,
      and the cells thus harvested from the rats can differentiate but cannot multiply
      in the same manner as the original culture-adapted bloodstream forms. Apparently,
      a certain variant has been selected during the adaptation of T. brucei
      bloodstream forms from rat blood to the culture medium. This variant could be a
      useful tool for identifying the genes involved in differentiation of T. brucei
      and multiplication of the procyclic forms. Comparison of the protein profiles
      between the wild-type and the variant during differentiation showed that a major
      protein band of about 70 kDa remained in the non-dividing variant procyclic forms
      but vanished in the rapidly dividing wild type procyclic forms. N-terminal
      determinations indicated that the 70-kDa protein band consists of bovine serum
      albumin and fetuin. Presumably these two serum proteins are actively taken up by
      the bloodstream forms via endocytosis. Since the procyclic forms are incapable of
      endocytosis, the serum proteins may be rapidly diluted in the growing wild type
      procyclic cells but remain unchanged in the non-dividing procyclic cells of the
      variant. Further studies are underway in trying to identify the key distinctions
      between these two lines of cells at the molecular level.

PMID- 8538692
TI  - The structure of the large subunit rRNA expressed in blood stages of Plasmodium
      falciparum.
AB  - Here we present the sequence of the large subunit (LSU) rRNA expressed in blood
      stage forms (and therefore A-type) of the malaria parasite, Plasmodium
      falciparum, from two different isolates. We determined the genomic sequence of a
      rRNA unit of the CAMP parasite strain from within the internal transcribed spacer
      1 (ITS1) through the 5.8S rRNA gene, the ITS2 and the entire large subunit rRNA
      gene. We have also determined the corresponding sequence of the gene of the FVO
      strain by sequencing cDNA clones derived from blood-stage asexual parasites.
      Differences between the two were due to scattered point mutations in expansion
      segments of the mature rRNA regions. In addition to the point mutations, the rRNA
      genes from the two strains could be distinguished by the presence of a more
      complex polymorphism near the 3' end of the molecule. The most complex
      polymorphic form was localized on a single chromosome and found in only a subset
      of geographically distinct isolates. The sequences of the 5.8S rRNA unit and the
      LSU rRNA unit reported here can be logically assembled into a complete secondary
      structure which conforms to the standard structure conserved in all eukaryotic
      ribosomes. The construction of a model of secondary structure for the LSU rRNA
      has allowed the identification of phylogenetically conserved sequences involved
      in drug interaction with the ribosome, as well as those sequences involved in
      tertiary interactions within the rRNA itself.

PMID- 8538693
TI  - Transient expression mediated by the Trypanosoma cruzi rRNA promoter.
AB  - Plasmid constructs containing a putative Trypanosoma cruzi rRNA promoter and
      transcription start point upstream from the bacterial chloramphenicol
      acetyltransferase (CAT) reporter gene were transfected into cultured T. cruzi
      epimastigotes to verify the presence of a promoter activity. Constructs bearing
      the putative promoter and a 3' trans-splicing acceptor site in the proper
      orientation yielded approx. two orders of magnitude greater CAT expression than
      that previously observed with the T. cruzi spliced leader (SL) gene promoter. In
      contrast, similar constructs lacking the known 3' splice site yielded reduced but
      readily measurable expression suggesting that sequences near the promoter may
      function as cryptic 3' splice sites. A repeated sequence upstream from the
      putative basal rRNA promoter in a position analogous to rRNA gene enhancer
      elements in other eukaryotes did not enhance expression from the T. cruzi rRNA
      promoter. Finally, these constructs were functional in some but not all T. cruzi
      isolates, and were inactive in other kinetoplastid species, suggesting that the
      T. cruzi rRNA promoter may have a limited host range.

PMID- 8538694
TI  - Cloning and sequencing of an excretory/secretory antigen from Ostertagia
      ostertagi fourth-stage larvae containing multiple tandem repeats.

PMID- 8538695
TI  - Evidence for proteolytic processing of a cuticle collagen in a plant-parasitic
      nematode.

PMID- 8538696
TI  - Purification and partial characterization of the cytosolic malate dehydrogenase
      from protoscolices of Echinococcus granulosus.

PMID- 8538697
TI  - Molecular cloning and expression of an immunodominant 53-kDa excretory-secretory
      antigen from Trichinella spiralis muscle larvae.

PMID- 8538698
TI  - The putative promoter for a metacyclic VSG gene in African trypanosomes.
AB  - During their metacyclic developmental stage, African trypanosomes are coated with
      one of 12-15 variant surface glycoproteins (VSGs) that define different
      metacyclic variant antigen types (MVATs). The MVAT VSG genes are located near
      telomeres of large chromosomes and are expressed without rearrangement in the
      metacyclic stage. We have cloned and examined the telomere-linked MVAT5 VSG gene
      and its upstream expression site associated gene (ESAG I) which are separated by
      4.5 kb. Within this 4.5-kb intergenic region is an 87-bp sequence that serves as
      a strong promoter for a luciferase reporter gene in transient transfection
      assays. This 87-bp sequence is similar, but not identical, to the promoter for
      another MVAT VSG gene. UV irradiation experiments were used to detect RNA
      synthesis from this MVAT5 promoter in bloodstream trypanosomes expressing an
      unrelated VSG. We propose that this sequence is a specific promoter for the MVAT5
      VSG mRNA that occurs in about 10% of the trypanosome population during the
      metacyclic stage of the parasites' life cycle.

PMID- 8538699
TI  - Free radical detoxification in Giardia duodenalis.
AB  - Non-denaturing polyacrylamide gels were used to analyse superoxide dismutase
      (SOD), catalase, peroxidase, NADH oxidase and NADH peroxidase in the
      microaerophilic protozoan parasite Giardia duodenalis. A cytosolic H2O-producing
      NADH oxidase and membrane-associated NADH peroxidase were readily detected from
      G. duodenalis. In all Giardia strains investigated the NADH oxidase was present
      in high levels (1.2-2 U (mg protein)-1). Using the same technique, NADH oxidase
      activity was also detected in the microaerophilic protozoan parasites
      Tritrichomonas foetus, Trichomonas vaginalis and Entamoeba histolytica and in the
      bacterium Escherichia coli. The conventional enzymes of oxidative stress
      management (superoxide dismutase, catalase and peroxidase) were not detected in
      particulate or cytosolic extracts from recent and established strains of Giardia
      assayed in situ. Spectrophotometric assays also yielded negative results. The
      same methodology readily detected one or more of these enzyme activities in T.
      foetus, T. vaginalis and E. coli. Superoxide dismutase activity was not detected
      in lines of Giardia resistant to high levels of metronidazole or furazolidone.
      Furthermore, the agents 1,10 phenanthroline, diamide, MnCl2 and KNO3, which
      induce SOD in anaerobically cultured E. coli, did not induce SOD in Giardia. 1,10
      phenanthroline has also been shown to induce iron-containing (Fe-) SOD in
      Entamoeba. Neither peroxidase nor catalase activities were detected in a peroxide
      resistant line of Giardia. Viable trophozoites from parent lines were able to
      decompose H2O2 at a significant rate. It appears that the conventional SOD,
      catalase and peroxidase utilised in aerobic metabolism have been substituted in
      Giardia by NADH oxidase and NADH peroxidase, similar to anaerobic bacteria. The
      O2-scavenging NADH oxidase explains the previously observed futile 'respiration'
      in Giardia.

PMID- 8538700
TI  - Purification and characterization of gamma-glutamylcysteine synthetase from
      Ascaris suum.
AB  - We have purified and characterized the Ascaris suum gamma-glutamylcysteine
      synthetase, the rate-limiting step in the glutathione biosynthesis. The purified
      enzyme exhibited a specific activity of 18 U (mg protein)-1. Estimation of the
      molecular mass of the native enzyme by FPLC on Superdex S-200 revealed the
      presence of two enzyme activity peaks corresponding to molecular masses of 100
      and 70 kDa. The higher-molecular-mass component could be dissociated by repeated
      gel filtration into the 70-kDa protein which is the enzymatically active subunit.
      The apparent Km values of the A. suum enzyme for L-aminobutyrate, L-cysteine and
      L-glutamate were 0.31, 0.41 and 0.94 mM, respectively. D,L-Buthionine-S,R
      sulfoximine and cystamine showed time-dependent irreversible inhibitory effects
      on the A. suum enzyme activity with Ki values of 0.05 and 1.11 microM,
      respectively. The Ki values for the corresponding enzyme from rat kidney with D,L
      buthionine-S,R-sulfoximine and cystamine were 7.19 and 22.2 microM, respectively.
      The time of half-inactivation of the enzyme at infinite concentration of D,L
      buthionine-S,R-sulfoximine, tau 50, was determined to be 3.1 and 1.34 min, for
      the parasite and mammalian enzymes respectively. For cystamine, a tau 50 value of
      3.32 min for the A. suum gamma-glutamylcysteine synthetase was determined, while
      a value of 2 min in case of rat kidney enzyme was found. The A. suum enzyme
      activity was competitively inhibited by glutathione with a Ki value of 0.11
      mM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538701
TI  - RNA-protein interactions in the ribonucleoprotein T-complexes in a mitochondrial
      extract from Leishmania tarentolae.
AB  - We have investigated protein-RNA interactions and the incorporation of [alpha
      32P]UTP into the guide RNA and mRNA components of the 'T-complexes' in a
      mitochondrial extract from Leishmania tarentolae. The terminal uridylyl
      transferase-containing complex T-IV is probably involved in the maturation of the
      3'-oligo(U) tail of the gRNAs, but the biological function and biochemical nature
      of the remaining T-complexes is not known. We have found that the relative extent
      of labeling of the RNA components is dependent on the UTP concentration: at low
      levels, the main endogenous RNA components labeled are the gRNAs in T-IV; at
      higher levels, the mRNAs in all of the T-complexes are preferentially labeled. We
      also show a tentative correlation in the migration pattern of UTP-labeled T
      complexes and complexes which bind exogenous labeled RNA. The relative extent of
      binding to specific complexes is dependent upon the type of RNA. Most of the
      interactions between the labeled RNAs and proteins can be disrupted by heparin or
      a large excess of rRNA, but two labeled complexes were resistant to competition.
      Most of the binding of labeled exogenous gRNA is disrupted by competition with a
      large excess of rRNA, but predigestion of the extract with micrococcal nuclease
      and saturation with rRNA uncovered a high affinity complex, which involves at
      least two proteins interacting with the bound gRNAs. A knowledge of the RNA and
      protein components may aid in understanding the biological roles of these RNP
      complexes.

PMID- 8538702
TI  - Extensive diversity in repeat unit sequences of the cDNA encoding the polyprotein
      antigen/allergen from the bovine lungworm Dictyocaulus viviparus.
AB  - The complete sequence of the cDNA encoding the nematode polyprotein
      allergen/antigen (NPA) of the bovine lungworm Dictyocaulus viviparus was obtained
      by immunoscreening of cDNA expression libraries and by 5' RACE (rapid
      amplification of cDNA ends). The encoded polypeptide is similar in sequence to
      the ABA-1 allergen of Ascaris, the gp15/400 'ladder' protein of Brugia malayi,
      Brugia pahangi and Wuchereria bancrofti, and a 15-kDa antigen of Dirofilaria
      immitis. As with these, the predicted amino-acid sequence comprises a head-to
      tail array of similar polypeptides with regularly spaced consensus proteinase
      cleavage sites. The D. viviparus protein was designated DvA-1 (D. viviparus
      antigen-1) and the gene dva-1. The deduced amino-acid sequence of DvA-1 showed
      features not observed before in other NPAs: (i) a hydrophobic leader peptide is
      present, (ii) none of the 12 units in the array are identical and the sequences
      diverge to a degree hitherto unseen in the NPAs of other nematode parasites,
      (iii) the predicted proteinase cleavage sites are also diverse in sequence and,
      in two instances, no consensus cleavage site was identifiable at the expected
      position, (iv) a short repeat unit is present, which is the only one containing a
      consensus N-glycosylation site and (v) a C-terminal extension peptide is encoded
      which shows no similarity to that from A. suum ABA-1. Comparison of independent
      cDNAs revealed slight variations in the sequence of the gene within the parasite
      population. Antisera to recombinant DvA-1 polypeptide identified 14-15-kDa
      antigens in both parasite somatic and excretory-secretory material. DvA-1 is the
      only NPA for which the complete coding sequence is available and the new
      principles which it illustrates may lie unsuspected in the NPA-encoding genes of
      all nematode parasites.

PMID- 8538703
TI  - Genetic diversity and population structure of Trypanosoma brucei: clonality
      versus sexuality.
AB  - Genomic fingerprinting by arbitrarily primed PCR was used to analyze the genetic
      variability among 59 Trypanosoma brucei stocks representing the three T. brucei
      subspecies isolated from various hosts and different countries in Africa. 14
      oligonucleotide primers revealed 355 polymorphic binary characters which were
      used for phenetic and phylogenetic analysis and to perform recombination tests
      exploring the linkage disequilibrium in the sample. There was good concordance
      between arbitrarily primed PCR polymorphisms and isoenzyme data previously
      collected for many of the same strains [1]. However, the arbitrarily primed PCR
      typing was more discerning than multilocus enzyme electrophoresis typing.
      Phenetic and phylogenetic analysis using arbitrarily primed PCR markers did not
      confirm T. brucei brucei and T. brucei rhodesiense as separate subspecies, but T.
      brucei gambiense group I was monophyletic, confirming this group as suitable for
      the subspecies status. With this exception, there were no clear lineages among
      the sample, other than clustering of East African stocks and clustering of West
      African stocks. Some features of the phylogenetic analysis suggested that the
      population structure was not strictly clonal though recombination tests showed
      linkage disequilibrium, even in the absence of repeated genotypes. While
      genotypes appear stable enough for tracking in applied studies, sexuality will
      impact at the evolutionary time scale, and may be more frequent under some
      ecological conditions. The arbitrarily primed PCR approach should be an effective
      and simple approach to follow epidemics and to quantify the role of sexuality in
      T. brucei populations.

PMID- 8538704
TI  - A controlled trial of two acellular vaccines and one whole-cell vaccine against
      pertussis. Progetto Pertosse Working Group.
AB  - BACKGROUND: Concern about both safety and efficacy has made the use of whole-cell
      pertussis vaccines controversial. In some European countries, including Italy,
      the rate of vaccination against pertussis is low. METHODS: We conducted a double
      blind trial in Italy in which infants were randomly assigned to vaccination at
      two, four, and six months of age with an acellular pertussis vaccine together
      with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell
      pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus
      toxoids without pertussis (DT). The acellular DTP vaccine was either one
      containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated
      with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous
      hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron
      Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with
      infection confirmed by culture or serologic testing. RESULTS: The efficacy of
      each vaccine, given in three doses, against pertussis was determined for 14,751
      children over an average of 17 months, with cases included in the analysis if
      cough began 30 days or more after the completion of immunization. For both of the
      acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence
      intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline
      DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95
      percent confidence interval, 14 to 52 percent). The antibody responses were
      greater to the acellular vaccines than to the whole-cell vaccine. Local and
      systemic adverse events were significantly more frequent after the administration
      of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse
      events was similar to that in the control (DT) group. CONCLUSIONS: The two
      acellular DTP vaccines we studied were safe, immunogenic, and efficacious against
      pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly
      low.

PMID- 8538705
TI  - A controlled trial of a two-component acellular, a five-component acellular, and
      a whole-cell pertussis vaccine.
AB  - BACKGROUND: Because of concern about safety and efficacy, no pertussis vaccine
      has been included in the vaccination program in Sweden since 1979. To provide
      data that might permit the reintroduction of a pertussis vaccine, we conducted a
      placebo-controlled trial of two acellular and one whole-cell pertussis vaccines.
      METHODS: After informed consent was obtained, 9829 children born in 1992 were
      randomly assigned to receive one of four vaccines: a two-component acellular
      diphtheria-tetanus-pertussis (DTP) vaccine (2566 children), a five-component
      acellular DTP vaccine (2587 children), a whole-cell DTP vaccine licensed in the
      United States (2102 children), or (as a control) a vaccine containing diphtheria
      and tetanus toxoids (DT) alone (2574 children). The vaccines were given at 2, 4,
      and 6 months of age, and the children were then followed for signs of pertussis
      for an additional 2 years (to a mean age of 21/2 years). RESULTS: The whole-cell
      vaccine was associated with significantly higher rates of protracted crying,
      cyanosis, fever, and local reactions than the other three vaccines. The rates of
      adverse events were similar for the acellular vaccines and the control DT
      vaccine. After three doses, the efficacy of the vaccines with respect to
      pertussis linked to a laboratory-confirmed case of pertussis or contact with an
      infected household member with paroxysmal cough for > or = 21 days was 58.9
      percent for the two-component vaccine (95 percent confidence interval, 50.9 to
      65.9 percent), 85.2 percent for the five-component vaccine (95 percent confidence
      interval, 80.6 to 88.8 percent), and 48.3 percent for the whole-cell vaccine (95
      percent confidence interval, 37.0 to 57.6 percent). CONCLUSIONS: The five
      component acellular pertussis vaccine we evaluated can be recommended for general
      use, since it has a favorable safety profile and confers sustained protection
      against pertussis. The two-component acellular vaccine and the whole-cell vaccine
      were less efficacious.

PMID- 8538706
TI  - Cohort studies of fat intake and the risk of breast cancer--a pooled analysis.
AB  - BACKGROUND: Experiments in animals, international correlation comparisons, and
      case-control studies support an association between dietary fat intake and the
      incidence of breast cancer. Most cohort studies do not corroborate the
      association, but they have been criticized for involving small numbers of cases,
      homogeneous fat intake, and measurement errors in estimates of fat intake.
      METHODS: We identified seven prospective studies in four countries that met
      specific criteria and analyzed the primary data in a standardized manner. Pooled
      estimates of the relation of fat intake to the risk of breast cancer were
      calculated, and data from study-specific validation studies were used to adjust
      the results for measurement error. RESULTS: Information about 4980 cases from
      studies including 337,819 women was available. When women in the highest quintile
      of energy-adjusted total fat intake were compared with women in the lowest
      quintile, the multivariate pooled relative risk of breast cancer was 1.05 (95
      percent confidence interval, 0.94 to 1.16). Relative risks for saturated,
      monounsaturated, and polyunsaturated fat and for cholesterol, considered
      individually, were also close to unity. There was little overall association
      between the percentage of energy intake from fat and the risk of breast cancer,
      even among women whose energy intake from fat was less than 20 percent.
      Correcting for error in the measurement of nutrient intake did not materially
      alter these findings. CONCLUSIONS: We found no evidence of a positive association
      between total dietary fat intake and the risk of breast cancer. There was no
      reduction in risk even among women whose energy intake from fat was less than 20
      percent of total energy intake. In the context of the Western lifestyle, lowering
      the total intake of fat in midlife is unlikely to reduce the risk of breast
      cancer substantially.

PMID- 8538707
TI  - Brief report: deficiency of a dystrophin-associated glycoprotein (adhalin) in a
      patient with muscular dystrophy and cardiomyopathy.

PMID- 8538708
TI  - Images in clinical medicine. Membranoproliferative glomerulonephritis type 1.

PMID- 8538709
TI  - Relationships between academic institutions and industry in the life sciences--an
      industry survey.
AB  - BACKGROUND: Despite growing acceptance of relationships between academia and
      industry in the life sciences, systematic, up-to-date information about their
      extent and the consequences for the parties involved remains scarce. We attempted
      to collect information about the prevalence, magnitude, commercial benefits, and
      potential risks of such relationships by surveying a representative sample of
      life-science companies in the United States to determine their relationships with
      academic institutions. METHODS: We collected data by telephone from May through
      September 1994 from senior executives of 210 life-science companies (of 306
      companies surveyed; response rate, 69 percent). The sample contained all Fortune
      500 companies in the fields of agriculture, chemicals, and pharmaceuticals; all
      international pharmaceutical companies with sales volumes similar to those of the
      Fortune 500 companies; and a random sample of non-Fortune 500 companies in the
      life sciences drawn from multiple commercial and noncommercial directories. Both
      the survey instrument and the survey methods resembled those of our 1984 study of
      106 biotechnology companies, allowing us to assess the evolution of relationships
      between academia and industry over the past decade. RESULTS: Ninety percent of
      companies conducting life-science research in the United States had relationships
      involving the life sciences with an academic institution in 1994. Fifty-nine
      percent supported research in such institutions, providing an estimated $1.5
      billion, or approximately 11.7 percent of all research-and-development funding
      received that year. The agreements with universities tended to be short-term and
      to involve small amounts, implying that most such relationships supported applied
      research or development. Over 60 percent of companies providing support for life
      science research in universities had received patents, products, and sales as a
      result of those relationships. At the same time, the companies reported that
      their relationships with universities often included agreements to keep the
      results of research secret beyond the time needed to file a patent. From 1984 to
      1994, the involvement of industry with academic institutions has increased, but
      the characteristics of the relationships have remained remarkably stable.
      CONCLUSIONS: After more than a decade of sustained interaction, universities and
      industries seem to have formed durable partnerships in the life sciences,
      although the relationships may pose greater threats to the openness of scientific
      communication than universities generally acknowledge. However, industrial
      support for university research is much smaller in amount than federal support,
      and companies are unlikely to be able to compensate for sizable federal cutbacks.

PMID- 8538710
TI  - Hypertension and associated metabolic abnormalities--the role of insulin
      resistance and the sympathoadrenal system.

PMID- 8538711
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 4-1996. A 40-year-old woman with the rapid onset of flaccid
      paraplegia.

PMID- 8538712
TI  - Acellular pertussis vaccines for infants.

PMID- 8538713
TI  - Secrecy in medical research.

PMID- 8538714
TI  - Benefits and hazards of reporting medical outcomes publicly.

PMID- 8538715
TI  - Methotrexate and misoprostol to terminate early pregnancy.

PMID- 8538716
TI  - Methotrexate and misoprostol to terminate early pregnancy.

PMID- 8538717
TI  - Methotrexate and misoprostol to terminate early pregnancy.

PMID- 8538718
TI  - Methotrexate and misoprostol to terminate early pregnancy.

PMID- 8538719
TI  - Drugs in cardiac transplantation.

PMID- 8538720
TI  - Drugs in cardiac transplantation.

PMID- 8538721
TI  - Vaccination against influenza in healthy adults.

PMID- 8538722
TI  - Vaccination against influenza in healthy adults.

PMID- 8538723
TI  - Vaccination against influenza in healthy adults.

PMID- 8538724
TI  - Immunoglobulin V genes in Reed-Sternberg cells.

PMID- 8538725
TI  - Immunoglobulin V genes in Reed-Sternberg cells.

PMID- 8538726
TI  - Immunoglobulin V genes in Reed-Sternberg cells.

PMID- 8538727
TI  - Medical disorders of alcoholism.

PMID- 8538728
TI  - Lego asthma.

PMID- 8538729
TI  - ORI defended.

PMID- 8538731
TI  - Biosafety regulations.

PMID- 8538730
TI  - Unesco and population genetics.

PMID- 8538733
TI  - O brave new words...

PMID- 8538732
TI  - Blood products.

PMID- 8538734
TI  - Eighteen-ninety-six and all that.
AB  - This year's commemorative platter includes ether anaesthesia, smallpox
      vaccination, radioactivity and several mathematical morsels, as well as an
      accidental death (Otto Lilienthal) and the mother of all births (the Universe).

PMID- 8538735
TI  - Life (and death) in a malignant tumour.

PMID- 8538736
TI  - Vision. When colours move.

PMID- 8538737
TI  - Analgesic effects of myrrh.

PMID- 8538738
TI  - Illusory motion from shadows.

PMID- 8538739
TI  - The crystal structure of the GroES co-chaperonin at 2.8 A resolution.
AB  - The GroES heptamer forms a dome, approximately 75 A in diameter and 30 A high,
      with an 8 A orifice in the centre of its roof. The 'mobile loop' segment,
      previously identified as a GroEL binding determinant, is disordered in the
      crystal structure in six subunits; the single well-ordered copy extends from the
      bottom outer rim of the GroES dome, suggesting that the cavity within the dome is
      continuous with the polypeptide binding chamber of GroEL in the chaperonin
      complex.

PMID- 8538740
TI  - Political uncertainty delays EMBL decision.

PMID- 8538741
TI  - A member of the KNOTTED class of homeodomain proteins encoded by the STM gene of
      Arabidopsis.
AB  - The KNOTTED class of plant genes encodes homeodomain proteins. These genes have
      been found in all plant species where they have been sought and, where examined,
      show expression patterns that suggest they play an important role in shoot
      meristem function. Until now, all mutant phenotypes associated with these genes
      have been due to gain-of-function mutations, making it difficult to deduce their
      wild-type function. Here we present evidence that the Arabidopsis SHOOT
      MERISTEMLESS (STM) gene, required for shoot apical meristem formation during
      embryogenesis, encodes a class I KNOTTED-like protein. We also describe the
      expression pattern of this gene in the wild-type plant. To our knowledge, STM is
      the first gene shown to mark a specific pattern element in the developing plant
      embryo both phenotypically and molecularly.

PMID- 8538742
TI  - A role for glucagon-like peptide-1 in the central regulation of feeding.
AB  - The sequence of glucagon-like peptide-1 (7-36) amide (GLP-1) is completely
      conserved in all mammalian species studied, implying that it plays a critical
      physiological role. We have shown that GLP-1 and its specific receptors are
      present in the hypothalamus. No physiological role for central GLP-1 has been
      established. We report here that intracerebroventricular (ICV) GLP-1 powerfully
      inhibits feeding in fasted rats. ICV injection of the specific GLP-1-receptor
      antagonist, exendin (9-39), blocked the inhibitory effect of GLP-1 on food
      intake. Exendin (9-39) alone had no influence on fast-induced feeding but more
      than doubled food intake in satiated rats, and augmented the feeding response to
      the appetite stimulant, neuropeptide Y. Induction of c-fos is a marker of
      neuronal activation. Following ICV GLP-1 injection, c-fos appeared exclusively in
      the paraventricular nucleus of the hypothalamus and central nucleus of the
      amygdala, and this was inhibited by prior administration of exendin (9-39). Both
      of these regions of the brain are of primary importance in the regulation of
      feeding. These findings suggest that central GLP-1 is a new physiological
      mediator of satiety.

PMID- 8538743
TI  - Rapid colour-specific detection of motion in human vision.
AB  - The human visual system is much better at analysing the motion of luminance
      (black and white) patterns than it is at analysing the motion of colour patterns,
      especially if the pattern is presented very briefly or moves rapidly. We report
      here that observers reliably distinguish the direction of motion of a colour
      pattern presented for only 17 milliseconds, provided that the contrast is several
      times the threshold value (the contrast needed to detect the presence of the
      pattern). A control experiment, in which a static luminance 'mask' is added to
      the moving colour pattern, proves that discrimination of the direction of motion
      of these brief stimuli is colour-specific. The mask drastically impairs
      discrimination of the direction of motion of a luminance pattern, but it has
      little effect on a colour pattern. We conclude that the human visual system
      contains colour-specific motion-detection mechanisms that are capable of
      analysing very brief signals.

PMID- 8538744
TI  - Activation of K+ channels and suppression of neuronal activity by secreted beta
      amyloid-precursor protein.
AB  - The Alzheimer's beta-amyloid precursor protein (beta-APP) is widely expressed in
      neural cells, and in neurons secreted forms of beta-APP (sAPPs) are released from
      membrane-spanning holo-beta APP in an activity-dependent manner. Secreted APPs
      can modulate neurite outgrowth, synaptogenesis, synaptic plasticity and cell
      survival; a signal transduction mechanism of sAPPs may involve modulation of
      intracellular calcium levels ([Ca2+]i). Here we use whole-cell perforated patch
      and single-channel patch-clamp analysis of hippocampal neurons to demonstrate
      that sAPPs suppress action potentials and hyperpolarize neurons by activating
      high-conductance, charybdotoxin-sensitive K+ channels. Activation of K+ channels
      by sAPPs was mimicked by a cyclic GMP analogue and sodium nitroprusside and
      blocked by an antagonist of cGMP-dependent kinase and a phosphatase inhibitor,
      suggesting that the effect is mediated by cGMP and protein dephosphorylation.
      Calcium imaging studies indicate that activation of K+ channels mediates the
      ability of sAPPs to decrease [Ca2+]i. Modulation of neuronal excitability may be
      a major mechanism by which beta-APP regulates developmental and synaptic
      plasticity in the nervous system.

PMID- 8538745
TI  - Regulation of glutamate release by presynaptic kainate receptors in the
      hippocampus.
AB  - Most reported actions of kainate are mediated by AMPA (alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionate) receptors. Here we report that, unlike AMPA which
      stimulates, kainate elicits a dose-dependent decrease in L-glutamate release from
      rat hippocampal synaptosomes and also depresses glutamatergic synaptic
      transmission. Brief exposure to kainate inhibited Ca(2+)-dependent [3H]L
      glutamate release by up to 80%. Inhibition was reversed by kainate antagonists
      but not by the AMPA-selective non-competitive antagonist 1-(4-aminophenyl)-4
      methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466). A corresponding
      reversible kainate-evoked depression of NMDA (N-methyl-D-aspartate) receptor
      mediated excitatory postsynaptic currents (e.p.s.cs) was observed when AMPA
      receptors were blocked by GYKI 52466. The synaptic depression was preceded by a
      brief period of enhanced release and a small inward current was also observed.
      The effects of kainate were unaffected by metabotropic glutamate (mGlu), GABAA,
      GABAB, glycine and adenosine receptor antagonists. These results indicate that
      glutamate release can be modulated directly by kainate autoreceptors.

PMID- 8538746
TI  - Defective thymocyte proliferation and IL-2 production in transgenic mice
      expressing a dominant-negative form of CREB.
AB  - The basic/leucine zipper (bZip) transcription factor, CREB, binds to the CRE
      element (TGANNTCA). The transcriptional activity of CREB requires phosphorylation
      of the protein on a serine residue at position 119 (ref. 6). CREs are present in
      a number of T-cell genes but the precise role of CREB in T-cell differentiation
      and function was unknown. Here we show that resting thymocytes contain
      predominantly unphosphorylated (inactive) CREB, which is rapidly activated by
      phosphorylation on Ser 119 following thymocyte activation. T-cell development is
      normal in transgenic mice that express a dominant-negative form of CREB
      (CREBA119, with alanine at position 119) under the control of the T-cell-specific
      CD2 promoter/enhancer. In contrast, thymocytes and T cells from these animals
      display a profound proliferative defect characterized by markedly decreased
      interleukin-2 production, G1 cell-cycle arrest and subsequent apoptotic death in
      response to a number of different activation signals. This proliferative defect
      is associated with the markedly reduced induction of c-jun, c-fos, Fra-2 and FosB
      following activation of the CREBA119 transgenic thymocytes. We propose that T
      cell activation leads to the phosphorylation and activation of CREB, which in
      turn is required for normal induction of the transcription factor AP1 and
      subsequent interleukin-2 production and cell-cycle progression.

PMID- 8538747
TI  - Sensitization of cells and retroviruses to human serum by (alpha 1-3)
      galactosyltransferase.
AB  - Mammalian C-type retroviruses are inactivated by human serum, following
      triggering of the classical complement cascade. This may have inhibited
      transmission to humans of C-type oncoviruses from other mammals. Indeed, the
      retroviruses human immunodeficiency virus and human T-cell leukaemia virus are
      resistant to human complement. Antibody-independent activation of human C1q, the
      first component of the classical pathway, by retroviral envelope proteins has
      been described. However, retroviruses produced from human cells are resistant to
      inactivation by human complement and human serum is known to contain antibodies
      directed against carbohydrates on retroviral envelopes. Gal(alpha 1-3)Gal
      terminal carbohydrates are expressed by most mammals but are absent in humans,
      which lack a functional (alpha 1-3)galactosyltransferase gene. Here, we
      demonstrate that anti-Gal(alpha 1-3)Gal antibodies in human serum inactivate
      retroviruses produced from animal cells. Expression of porcine (alpha 1
      3)galactosyltransferase in human cells renders the cells and the retroviruses
      they produce sensitive to human serum.

PMID- 8538748
TI  - Hypoxia-mediated selection of cells with diminished apoptotic potential in solid
      tumours.
AB  - Apoptosis is a genetically encoded programme of cell death that can be activated
      under physiological conditions and may be an important safeguard against tumour
      development. Regions of low oxygen (hypoxia) and necrosis are common features of
      solid tumours. Here we report that hypoxia induces apoptosis in oncogenically
      transformed cells and that further genetic alterations, such as loss of the p53
      tumour-suppressor gene or overexpression of the apoptosis-inhibitor protein Bcl
      2, substantially reduce hypoxia-induced cell death. Hypoxia also selects for
      cells with defects in apoptosis, because small numbers of transformed cells
      lacking p53 overtake similar cells expressing wild-type p53 when treated with
      hypoxia. Furthermore, highly apoptotic regions strongly correlate with hypoxic
      regions in transplanted tumours expressing wild-type p53, whereas little
      apoptosis occurs in hypoxic regions of p53-deficient tumours. We propose that
      hypoxia provides a physiological selective pressure in tumours for the expansion
      of variants that have lost their apoptotic potential, and in particular for cells
      acquiring p53 mutations.

PMID- 8538749
TI  - Regulation of cell adhesion and anchorage-dependent growth by a new beta 1
      integrin-linked protein kinase.
AB  - The interaction of cells with the extracellular matrix regulates cell shape,
      motility, growth, survival, differentiation and gene expression, through integrin
      mediated signal transduction. We used a two-hybrid screen to isolate genes
      encoding proteins that interact with the beta 1-integrin cytoplasmic domain. The
      most frequently isolated complementary DNA encoded a new, 59K serine/threonine
      protein kinase, containing four ankyrin-like repeats. We report here that this
      integrin-linked kinase (ILK) phosphorylated a beta 1-integrin cytoplasmic domain
      peptide in vitro and coimmunoprecipitated with beta 1 in lysates of mammalian
      cells. Endogenous ILK kinase activity was reduced in response to fibronectin.
      Overexpression of p59ILK disrupted epithelial cell architecture and inhibited
      adhesion to integrin substrates, while inducing anchorage-independent growth. We
      propose that ILK is a receptor-proximal protein kinase regulating integrin
      mediated signal transduction.

PMID- 8538751
TI  - Agencies warn of grant delays as Washington returns to backlog.

PMID- 8538750
TI  - Conserved residues and the mechanism of protein folding.
AB  - Experimental and simulation studies show that small monomeric proteins fold in
      one kinetic step, which entails overcoming the free-energy barrier between the
      unfolded and the native protein through a transition state. Two models of
      transition state formation have been proposed: a 'nonspecific' one in which it
      depends on the formation of a sufficient number of native-like contacts
      regardless of what amino acids are involved, and a 'specific' one, in which it
      depends on formation of a specific subset of the native structure (a folding
      nucleus). The latter requires that some amino acids form most of their contacts
      in the transition state, whereas others only do so on reaching the native
      conformation. If so, mutations affecting the stability of the transition state
      nucleus should have a greater effect on the folding kinetics than mutations
      elsewhere, and the residues involved should be evolutionarily conserved. Lattice
      model simulations and experiments suggest that such mutations exist. Here we
      present a method for determining the folding nucleus of a protein with known
      structure with two-state folding kinetics. This method is based on the alignment
      of many sequences designed to fold into the native conformation of a protein to
      identify the positions where amino acids are most conserved in designed
      sequences. The method is applied to chymotrypsin inhibitor 2 (CI2), a protein
      whose transition state has been previously studied by protein engineering. The
      involvement of residues in folding nucleus of CI2 is clearly correlated with
      their conservation in design, and the residues forming the nucleus are highly
      conserved in 23 natural sequences homologous to CI2.

PMID- 8538752
TI  - Cancer charity spending comes under fire.

PMID- 8538753
TI  - Money woes fail to weaken Japan's support for science.

PMID- 8538754
TI  - Cancer fund likely to boost basic research under new director.

PMID- 8538756
TI  - Trusting in traditional cures.

PMID- 8538755
TI  - Change of diet unsettles nutrition research in Germany.

PMID- 8538757
TI  - Gene patenting.

PMID- 8538758
TI  - New chapter for the fat controller.

PMID- 8538759
TI  - X-chromosome inactivation. Pinpointing the centre.

PMID- 8538760
TI  - Palaeoanthropology. The nature of the evidence.

PMID- 8538761
TI  - Robustness of cooperation.

PMID- 8538762
TI  - Requirement for Xist in X chromosome inactivation.
AB  - The Xist gene has been proposed as a candidate for the X inactivation centre, the
      master regulatory switch locus that controls X chromosome inactivation. So far
      this hypothesis has been supported solely by indirect evidence. Here we describe
      gene targeting of Xist, and provide evidence for its absolute requirement in the
      process of X chromosome inactivation.

PMID- 8538764
TI  - A Dryopithecus skeleton and the origins of great-ape locomotion.
AB  - The evolution of skeletal adaptations to orthograde postures, characteristic of
      extant hominoids, is of great interest as it provides the key to understanding
      the origins of apes and humans. We report here the recent discovery of an
      extraordinary partial skeleton of Dryopithecus laietanus from Can Llobateres
      (Spain). It provides evidence that orthograde postures and locomotion appeared at
      least 9.5 million years ago. Our results indicate that the body structure of this
      Miocene ape closely resembles that of extant hominoids and differs from the
      pronograde pattern of Miocene proconsulids in a set of important morphological
      characters. Dryopithecus also shows more traits reflecting structural adaptations
      for suspension than occurs in African apes. A similar positional behaviour is
      inferred for Sivapithecus indicus, thus strengthening previous hypotheses linking
      both Miocene forms with Pongo.

PMID- 8538763
TI  - Experimental simulations of the photodecomposition of carbonates and sulphates on
      Mars.
AB  - There is indirect spectroscopic evidence for the presence of sulphates and
      carbonates on the martian surface, and such minerals are also found in SNC
      meteorites, which are thought to be of martian origin. But although carbonates
      are expected to be abundant in the martian regolith, attempts to detect them
      directly have been unsuccessful. Here we report laboratory studies of the
      decompostion of calcium carbonate and magnesium sulphate under ultraviolet
      irradiation, which mimic the conditions under which photodecomposition of surface
      minerals by solar ultraviolet light might occur on Mars. We find that, even for a
      low abundance of carbonate minerals in the martian regolith, the rate of CO2
      release due to photodecomposition is higher than the rate of CO2 loss from the
      atmosphere by solar-wind-induced sputtering processes, making this process a
      potential net source of atmospheric CO2 over time. SO2 is also released from the
      sulphate, albeit more slowly. The rate of carbonate degradation is high enough to
      explain the apparent absence of these compounds at the martian surface.

PMID- 8538765
TI  - Patterning of the Drosophila embryo by a homeodomain-deleted Ftz polypeptide.
AB  - Homeodomain proteins regulate diverse developmental processes in a wide range of
      organisms, yet bind in vitro to DNA sequences that are remarkably similar. This
      has raised the fundamental question of how target gene specificity is achieved in
      vivo. The Drosophila fushi tarazu protein (Ftz) contains a homeodomain and is
      required for the formation of alternate segments. We have shown previously that a
      homeodomain-deleted Ftz polypeptide (Ftz delta HD), incapable of binding DNA in
      vitro, could regulate endogenous ftz gene expression. Here we test Ftz delta HD
      activities in a ftz mutant background and find that, surprisingly, Ftz delta HD
      can directly regulate ftz-dependent segmentation, suggesting that it can control
      target gene expression through interactions with other proteins. A likely
      candidate is the pair-rule protein Paired (Prd). Ftz delta HD bound directly to
      Prd in vitro and required Prd to repress wingless in vivo. These results
      emphasize the pivotal importance of protein-protein interactions in homeodomain
      protein function.

PMID- 8538766
TI  - Early computation of shape and reflectance in the visual system.
AB  - A compelling sense of three-dimensional shape may be conveyed by the photograph
      of an object. Cues such as contour, shading, perspective and occlusion, to name a
      few, contribute to this percept. Psychophysical experiments suggest that certain
      aspects of three-dimensional shape are computed rapidly and in parallel by the
      visual system. Here we report that reflectance is also computed rapidly;
      moreover, it is the apparent reflectance, rather than brightness or perceptual
      three-dimensional shape, that is the primary basis for discrimination during the
      early stages of visual processing.

PMID- 8538767
TI  - Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate
      receptor.
AB  - The inositol 1,4,5-trisphosphate (InsP3) receptor acts as an InsP3-gated Ca2+
      release channel in a variety of cell types. Type 1 InsP3 receptor (IP3R1) is the
      major neuronal member of the IP3R family in the central nervous system,
      predominantly enriched in cerebellar Purkinje cells but also concentrated in
      neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex. Here
      we report that most IP3R1-deficient mice generated by gene targeting die in
      utero, and born animals have severe ataxia and tonic or tonic-clonic seizures and
      die by the weaning period. An electroencephalogram showed that they suffer from
      epilepsy, indicating that IP3R1 is essential for proper brain function. However,
      observation by light microscope of the haematoxylin-eosin staining of the brain
      and peripheral tissues of IP3R1-deficient mice showed no abnormality, and the
      unique electrophysiological properties of the cerebellar Purkinje cells of IP3R1
      deficient mice were not severely impaired.

PMID- 8538768
TI  - Modulation of non-vesicular glutamate release by pH.
AB  - Glutamate uptake into glial cells helps to keep the brain extracellular glutamate
      concentration, [glu]o, below levels that kill neurons. Uptake is powered by the
      transmembrane gradients of Na+, K+ and pH. When the extracellular [K+] rises in
      brain ischaemia, uptake reverses, releasing glutamate into the extracellular
      space. Here we show, by monitoring glutamate transport electrically and detecting
      released glutamate with ion channels in neurons placed outside glial cells, that
      a raised [H+] inhibits both forward and reversed glutamate uptake. No
      electroneutral reversed uptake was detected, contradicting the idea that forward
      and reversed uptake differ fundamentally. Suppression of reversed uptake by the
      low pH occurring in ischaemia will slow the Ca(2+)-independent release of
      glutamate with can raise [glu]o to a neurotoxic level, and will thus protect the
      brain during a transient loss of blood supply.

PMID- 8538769
TI  - Schwann cell apoptosis at developing neuromuscular junctions is regulated by
      glial growth factor.
AB  - Denervated adult mammalian muscle fibres are reinnervated by regenerating axons
      and, in the case of partially denervated muscles, by sprouts extended from
      remaining, intact axons. Recent experiments suggest that Schwann cells (SCs)
      regulate these events, inducing and guiding axonal outgrowth through the
      processes they extend. In contrast to adults, reinnervation o denervated neonatal
      muscles is deficient and axonal sprouting is absent. In light of the proposed
      roles for SCs in these processes, we examined whether SCs in neonatal muscles
      exhibit altered responses to denervation. We report here that neonatal
      denervation leads to the rapid, apoptotic death of SCs at rat neuro-muscular
      junctions. Injection of glial growth factor, a member of the neuregulin family of
      trophic factors present in developing sensory and motor neurons, prevents this
      apoptosis in vivo. These results provide further evidence for the importance of
      SCs in regulating nerve growth and suggest that axon-Schwann cell trophic
      interactions play a role in the normal development of the neuromuscular system.

PMID- 8538770
TI  - The reaction mechanism of the internal thioester in the human complement
      component C4.
AB  - A key step in the elimination of pathogens from the body is the covalent binding
      of complement proteins C3 and C4 to their surfaces. Proteolytic activation of
      these proteins results in a conformational change, and an internal thioester is
      exposed which reacts with amino or hydroxyl groups on the target surface to form
      amide or ester bonds, or is hydrolysed. We report here that the binding of the
      human C4A isotype involves a direct reaction between amino-nucleophiles and the
      thioester. A two-step mechanism is used by the C4B isotype. The histidine at
      position 1,106(aspartic acid in C4A) first attacks the thioester to form an acyl
      imidazole intermediate. The released thiol then acts as a base to catalyse the
      transfer of the acyl group to amino- and hydroxyl-nucleophiles, including water.

PMID- 8538771
TI  - An essential role for the Cdc6 protein in forming the pre-replicative complexes
      of budding yeast.
AB  - Origins of DNA replication in Saccharomyces cerevisiae are bound by two protein
      complexes during the cell cycle. Post-replicative complexes closely resemble
      those generated in vitro by purified origin recognition complex (ORC), which is
      essential for DNA replication in vivo. Pre-replicative complexes (pre-RCs) are
      characterized by an extended region of nuclease protection overlapping the ORC
      footprint. We show here that the Cdc6 protein (Cdc6p), which is necessary for
      origin firing in vivo, is essential for the establishment and maintenance of pre
      RCs, suggesting that it is a component of these complexes. Without Cdc6p, G1
      origins closely resemble post-replicative origins, providing evidence that ORC is
      also a component of pre-RCs. These results suggest that pre-RCs play an essential
      role in initiating DNA replication and support a two-step mechanism for the
      assembly of functional initiation complexes.

PMID- 8538772
TI  - Requirement of mammalian DNA polymerase-beta in base-excision repair.
AB  - Synthesis of DNA by DNA polymerase-beta is distributive on single-stranded DNA
      templates, but short DNA gaps with a 5' PO4 in the gap are filled processively to
      completion. In vitro studies have suggested a role of beta-polymerase in
      different types of DNA repair. However, the significance of these studies to the
      in vivo role of beta-polymerase has remained unclear. Because genetic studies are
      essential for determining the physiological role of a gene, we established
      embryonic fibroblast cell lines homozygous for a deletion mutation in the gene
      encoding DNA polymerase-beta. Extracts from these cell lines were found to be
      defective in uracil-initiated base-excision repair. The beta-polymerase-deleted
      cells are normal in viability and growth characteristics, although they exhibit
      increased sensitivity to monofunctional DNA-alkylating agents, but not to other
      DNA-damaging agents. Both the deficiency in base-excision repair and
      hypersensitivity to DNA-alkylating agents are rescued following stable
      transfection with a wild-type beta-polymerase minitransgene. These studies
      demonstrate that beta-polymerase functions specifically in base-excision repair
      in vivo.

PMID- 8538773
TI  - How not to be charitable.
AB  - A scandal in France reveals that large sums of money intended for cancer research
      have been misdirected. Scientists and government alike have failed colleagues and
      the public.

PMID- 8538774
TI  - Reinforcing access to research data.

PMID- 8538775
TI  - New director for Cambridge biology laboratory.

PMID- 8538776
TI  - A good year for US biotech, but caution is still advised.

PMID- 8538777
TI  - Charity head faces resignation calls.

PMID- 8538778
TI  - MPs challenge rejection of genetics panel.

PMID- 8538779
TI  - European debate on biotech highlights policy differences.

PMID- 8538780
TI  - Crystallographic data deposition.

PMID- 8538781
TI  - Panic and the pill.

PMID- 8538782
TI  - Planetary science. Martians in a deep freeze.

PMID- 8538783
TI  - Virology. New trick from an old foe.

PMID- 8538784
TI  - No diffusion barrier at axon hillock.

PMID- 8538785
TI  - PNA as a rare genome-cutter.

PMID- 8538786
TI  - Role of hydration and water structure in biological and colloidal interactions.
AB  - The conventional explanation of why hydrophilic surfaces and macromolecules
      remain well separated in water is that they experience a monotonically repulsive
      hydration force owing to structuring of water molecules at the surfaces. A
      consideration of recent experimental and theoretical results suggests an
      alternative interpretation in which hydration forces are either attractive or
      oscillatory, and where repulsions have a totally different origin. Further
      experiments are needed to distinguish between these possibilities.

PMID- 8538787
TI  - Structure and mechanism of DNA topoisomerase II.
AB  - The crystal structure of a large fragment of yeast type II DNA topoisomerase
      reveals a heart-shaped dimeric protein with a large central hole. It provides a
      molecular model of the enzyme as an ATP-modulated clamp with two sets of jaws at
      opposite ends, connected by multiple joints. An enzyme with bound DNA can admit a
      second DNA duplex through one set of jaws, transport it through the cleaved first
      duplex, and expel it through the other set of jaws.

PMID- 8538788
TI  - Synthesis of RNA oligomers on heterogeneous templates.
AB  - The concept of an RNA world in the chemical origin of life is appealing, as
      nucleic acids are capable of both information storage and acting as templates
      that catalyse the synthesis of complementary molecules. Template-directed
      synthesis has been demonstrated for homogeneous oligonucleotides that, like
      natural nucleic acids, have 3',5' linkages between the nucleotide monomers. But
      it seems likely that prebiotic routes to RNA-like molecules would have produced
      heterogeneous molecules with various kinds of phosphodiester linkages and both
      linear and cyclic nucleotide chains. Here we show that such heterogeneity need be
      no obstacle to the templating of complementary molecules. Specifically, we show
      that heterogeneous oligocytidylates, formed by the montmorillonite clay-catalysed
      condensation of actuated monomers, can serve as templates for the synthesis of
      oligoguanylates. Furthermore, we show that oligocytidylates that are exclusively
      2',5'-linked can also direct synthesis of oligoguanylates. Such heterogeneous
      templating reactions could have increased the diversity of the pool of
      protonucleic acids from which life ultimately emerged.

PMID- 8538789
TI  - Development of identical orientation maps for two eyes without common visual
      experience.
AB  - In the mammalian visual cortex, many neurons are driven binocularly and response
      properties such as orientation preference or spatial frequency tuning are
      virtually identical for the two eyes. A precise match of orientation is essential
      in order to detect disparity and is therefore a prerequisite for stereoscopic
      vision. It is not clear whether this match is accomplished by activity-dependent
      mechanisms together with the common visual experience normally received by the
      eyes, or whether the visual system relies on other, perhaps even innate, cues to
      achieve this task. Here we test whether visual experience is responsible for the
      match in a reverse-suturing experiment in which kittens were raised so that both
      eyes were never able to see at the same time. A comparison of the layout of the
      two maps formed under these conditions showed them to be virtually identical.
      Considering that the two eyes never had common visual experience, this indicates
      that correlated visual input is not required for the alignment of orientation
      preference maps.

PMID- 8538790
TI  - Conservation of hippocampal memory function in rats and humans.
AB  - The hippocampus is critical to declarative memory in humans. This kind of memory
      involves associations among items or events that can be accessed flexibly to
      guide memory expression in various and even new situations. In animals, there has
      been controversy about whether the hippocampus is specialized for spatial memory
      or whether it mediates a general memory function, as it does in humans. To
      address this issue we trained normal rats and rats with hippocampal damage on non
      spatial stimulus-stimulus associations, then probed the nature of their memory
      representations. We report here that normal rats demonstrated two forms of
      flexible memory expression, transitivity, the ability to judge inferentially
      across stimulus pairs that share a common element, and symmetry, the ability to
      associate paired elements presented in the reverse of training order. Rats with
      neurotoxic damage limited to the hippocampus demonstrated neither form of
      flexible expression, indicating that non-spatial declarative processing depends
      specifically on the hippocampus in animals as it does in humans.

PMID- 8538791
TI  - A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory
      neurons.
AB  - Dorsal root ganglion sensory neurons associated with C-fibres, many of which are
      activated by tissue-damage, express an unusual voltage-gated sodium channel that
      is resistant to tetrodotoxin. We report here that we have identified a 1,957
      amino-acid sodium channel in these cells that shows 65% identity with the rat
      cardiac tetrodotoxin-insensitive sodium channel, and is not expressed in other
      peripheral and central neurons, glia or non-neuronal tissues. In situ
      hybridization shows that the channel is expressed only by small-diameter sensory
      neurons in neonatal and adult dorsal root and trigeminal ganglia. The channel is
      resistant to tetrodotoxin when expressed in Xenopus oocytes. The
      electrophysiological and pharmacological properties of the expressed channel are
      similar to those described for the small-diameter sensory neuron tetrodotoxin
      resistant sodium channels. As some noxious input into the spinal cord is
      resistant to tetrodotoxin, block of expression or function of such a C-fibre
      restricted sodium channel may have a selective analgesic effect.

PMID- 8538792
TI  - Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice.
AB  - Activating transcription factor-2 (ATF-2) is a basic region leucine zipper
      protein whose DNA target sequence is the widely distributed cAMP response element
      (CRE). We report here that mice carrying a germline mutation in ATF-2
      demonstrated unique actions of ATF-2 not duplicated by other ATF/CREB family
      members. Mutant mice had decreased postnatal viability and growth, with a defect
      in endochondral ossification at epiphyseal plates similar to human
      hypochondroplasia. The animals had ataxic gait, hyperactivity and decreased
      hearing. In the brain, there were reduced numbers of cerebellar Purkinje cells,
      atrophic vestibular sense organs and enlarged ventricles. Unlike CREB alpha/delta
      deficient mice whose main defect is in long-term potentiation, the widespread
      abnormalities in ATF-2 mutant mice demonstrate its absolute requirement for
      skeletal and central nervous system development, and for maximal induction of
      select genes with CRE sites, such as E-selectin.

PMID- 8538793
TI  - Adhesion through L-selectin requires a threshold hydrodynamic shear.
AB  - Selectins are cell adhesion molecules that bind carbohydrate ligands and promote
      interaction between leukocytes and the vessel wall in vascular shear flow.
      Selectin-ligand bonds have high mechanical strength, allowing initial tethering
      to the vessel wall through one or few bonds, and have fast on and off rates,
      permitting rolling in response to hydrodynamic drag. The L-selectin molecule on
      leukocytes binds to peripheral node addressin on high endothelial venules of
      lymph nodes to mediate leukocyte rolling and binds to a ligand on neutrophils to
      mediate rolling of leukocytes over one another. Here we describe a surprising
      mechanism for regulation of these interactions, both in vitro and in vivo. Shear
      above a critical threshold is required to promote and maintain rolling
      interactions through L-selectin, but not through E-selectin, P-selectin or VCAM
      1. The shear threshold requirement for L-selectin may be physiologically
      important in low shear to prevent inappropriate aggregation of leukocytes and
      interaction with the vessel wall.

PMID- 8538794
TI  - A bipolar kinesin.
AB  - Chromosome segregation during mitosis depends on the action of the mitotic
      spindle, a self-organizing, bipolar protein machine which uses microtubules (MTs)
      and their associated motors. Members of the BimC subfamily of kinesin-related MT
      motor proteins are believed to be essential for the formation and functioning of
      a normal bipolar spindle. Here we report that KRP130, a homotetrameric BimC
      related kinesin purified from Drosophila melanogaster embryos, has an unusual
      ultrastructure. It consists of four kinesin-related polypeptides assembled into a
      bipolar aggregate with motor domains at opposite ends, analogous to a miniature
      myosin filament. Such a bipolar 'minifilament' could crosslink spindle MTs and
      slide them relative to one another. We do not know of any other MT motors that
      have a bipolar structure.

PMID- 8538797
TI  - ASN (American Society of Nephrology): the year ahead.

PMID- 8538795
TI  - Post-transcriptional transactivation of human retroviral envelope glycoprotein
      expression by herpes simplex virus Us11 protein.
AB  - Herpes simplex virus type 1 (HSV-1) Us11 protein, a true late gene product
      packaged within the virion, is delivered into cells after infection, exhibits a
      nucleocytoplasmic localization at early times, and later accumulates in the
      nucleoli. This RNA-binding basic phosphoprotein, capable of oligomerization, is
      supposed to be involved in post-transcriptional regulation of gene expression
      after HSV-1 infection. Expression of human T-cell leukaemia/lymphoma virus type-I
      (HTLV-I) and of human immunodeficiency virus type 1 (HIV-1) is post
      transcriptionally regulated by Rex and Rev, respectively. These proteins are
      required for the cytoplasmic expression of unspliced gag-pol and singly spliced
      env transcripts. Here we show that HSV-1 Us11 protein is able to bind Rex- and
      Rev-responsive elements and to transactivate envelope retroviral glycoprotein
      expression.

PMID- 8538798
TI  - Minorities and ESRD. Early identification of renal disease among African
      Americans: a continuing problem.

PMID- 8538796
TI  - Spatial constraints on the recognition of phosphoproteins by the tandem SH2
      domains of the phosphatase SH-PTP2.
AB  - The domain organization of many signalling proteins facilitates a segregation of
      binding, catalytic and regulatory functions. The mammalian SH2 domain protein
      tyrosine phosphatases (PTPs) contain tandem SH2 domains and a single carboxy
      terminal catalytic domain. SH-PTP1 (PTP1C, HCP) and SH-PTP2 (Syp, PTP2C, PTP1D)
      function downstream from tyrosine kinase-linked insulin, growth factor, cytokine
      and antigen receptors. As well as directing subcellular localization by binding
      to receptors and their substrates, the two SH2 domains of these PTPs function
      together to regulate catalysis. Here we report the structure of the tandem SH2
      domains of SH-PTP2 in complex with monophosphopeptides. A fixed relative
      orientation of the two domains, stabilized by a disulphide bond and a small
      hydrophobic patch within the interface, separates the peptide binding sites by
      approximately 40 A. The defined orientation of the SH2 domains in the structure,
      and data showing that peptide orientation and spacing between binding sites is
      critical for enzymatic activation, suggest that spatial constraints are important
      in this multidomain protein-protein interaction.

PMID- 8538799
TI  - Minorities and ESRD. Review: African American study of kidney disease and
      hypertension clinical trial.

PMID- 8538800
TI  - Launching CQI in ESRD: the starting point.

PMID- 8538801
TI  - Dialysis in the operating room: the St. Paul's experience.

PMID- 8538802
TI  - Using computers as clinical tools to improve patient care.

PMID- 8538803
TI  - Cardiac intervention for ESRD patients: what is the safest method?

PMID- 8538804
TI  - The war on poverty is over! The poor lost!

PMID- 8538805
TI  - An interview with Duane D. Walker. Interview by Connie R Curran.
AB  - Duane D. Walker, MS, RN, FAAN, is vice president of patient services and the
      executive director of the Nursing Institute at The Queen's Medical Center,
      Honolulu, Hawaii. In this interview he discusses the history of The Queen's
      Medical Center, multidisciplinary care, accountability, and careers in nursing
      management.

PMID- 8538806
TI  - Turnover of hospital chief nursing officers.
AB  - This study examined the factors contributing to chief nursing officer (CNO)
      turnover. Different reasons for departure were cited between the CNOs and chief
      executive officers. Perceptional differences also existed in salaries, job
      performance, and institutional effects of the departure.

PMID- 8538807
TI  - Impact of a CareMap and case management on patient satisfaction and staff
      satisfaction, collaboration, and autonomy.
AB  - The purpose of this research was to evaluate the effect of a CareMap and nursing
      case management on patient satisfaction and staff job satisfaction,
      collaboration, and autonomy. The patients who had a CareMap and a nurse case
      manager were more satisfied with their care. The multidisciplinary staff who
      worked on the experimental unit had increased job satisfaction and nurses who
      applied and were selected for case management positions had higher levels of
      collaboration and increased autonomy. Multidisciplinary team members who
      developed the CareMap also had higher levels of collaboration than other
      multidisciplinary staff on the experimental unit and their job satisfaction with
      quality of care increased under this new care delivery system.

PMID- 8538808
TI  - Nurse practitioners, cost savings, and improved patient care in the department of
      surgery.
AB  - As competition increases and health care demands continue to rise, it is
      essential to constantly evaluate the effectiveness of health care provided while
      delivering cost-effective care which is safe and results in quality outcomes. The
      addition of nurse practitioners to the department of surgery is not another layer
      of health care workers doing tasks, but rather it is a process. The role of nurse
      practitioners and the impact of cost savings and improved care in one department
      of surgery are described.

PMID- 8538809
TI  - Advance directives: the price of life.
AB  - Advance directives support the concepts of patient autonomy and resource
      allocation. Promotion of advance directives by nurse managers according to the
      suggested paradigm should be an economic and policy priority.

PMID- 8538810
TI  - Perspectives of practicing nurses on ethical issues in health care economics.
AB  - Perspectives of nurses working in seven hospitals across the United States are
      described. Most nurses believed that all people should have equal access and
      quality of health care. However, most nurses were unwilling to pay more taxes or
      donate time to achieve these goals.

PMID- 8538811
TI  - The effect of a partnership model on quality and length of stay.
AB  - The differences in patient length of stay and quality indicators pre and post
      implementation of a nursing partnership model were examined. Findings indicated
      no significant difference in length of stay, infection rates, medication or
      procedural errors, but significantly less falls after implementation. Length of
      stay decreased by 0.7 days.

PMID- 8538813
TI  - Professional image: what counts?

PMID- 8538812
TI  - Helicoptering, headlighting, and agility: the nurse manager's challenge.

PMID- 8538814
TI  - Medicaid and Medicare: parties battle over cuts.

PMID- 8538815
TI  - Leadership issues in perioperative nursing: the visionary nurse manager.

PMID- 8538816
TI  - Hypertension and target organ damage.

PMID- 8538817
TI  - Ambulatory blood pressure measurement and the occurrence of hypertensive organ
      involvement.
AB  - Target organ involvement in hypertensive patients carries a poor prognosis,
      especially echocardiographically demonstrated left ventricular hypertrophy.
      Conventional blood pressure measurement correlates with target organ damage and
      mortality. 24-Hour ambulatory blood pressure measurement (ABPM) is a better
      predictor of target organ involvement than conventional blood pressure
      measurement, but there is as yet only scant evidence that 24-hour ABPM predicts
      mortality. The techniques for assessing target organ involvement and the
      superiority of ABPM over conventional measurement in predicting target organ
      damage are reviewed. It is argued that if 24-hour ABPM predicts target organ
      damage better than conventional measurement, then the likelihood is that it will
      also be a better predictor of mortality than conventional measurement. The
      studies underway to determine this important issue are reviewed.

PMID- 8538818
TI  - Arterial distensibility and compliance in hypertension.
AB  - Under normal circumstances arteries, especially the larger elastic ones, distend
      during systole, and hence are able to store volume energy during this phase of
      the cardiac cycle. In this way the increase in blood pressure during systole will
      be leveled off. The amount of energy that can be stored depends not only on the
      degree of distension (distensibility), but also on the initial diameter of the
      vessel--two parameters actually determining the compliance of an artery. In both
      established and borderline hypertension distensibility and compliance of the
      larger elastic arteries are reduced, as compared with normotensives, but not of
      the radial artery, at least in patients with established hypertension. In these
      patients this artery shows a pronounced increase in intima-media thickness. The
      elastic modulus of the radial artery is not different in hypertensive and
      normotensive subjects. In the present state of the art, it cannot be concluded
      whether the loss of artery wall distensibility is caused solely by the increase
      in blood pressure or that also structural wall changes are involved. In
      borderline hypertensive patients distensibility and compliance of the elastic
      arteries are diminished as compared with normotensive subjects. The loss of
      distensibility already occurs in the fourth age decade and is not homogeneous
      along the carotid artery bifurcation. The distensibility is significantly lower
      at all levels in the carotid artery bulb than in the common carotid artery, the
      proximal part of the bulb, where the baroreceptors are predominantly located,
      being most affected. This pattern is similar to that observed in normotensive
      subjects in the sixth age decade, indicating that the carotid arteries age faster
      in borderline hypertensive than in normotensive subjects.

PMID- 8538819
TI  - Effects of antihypertensive drugs on large artery compliance.
AB  - The changes in arterial compliance following drug treatment have been studied
      mainly in hypertension. Physiologically, reduced arterial compliance
      independently affects blood pressure through an increase in systolic pressure and
      a decrease in diastolic pressure at any given value of mean arterial pressure.
      This review summarizes the pharmacological studies performed in recent years on
      the ability of antihypertensive drugs to modify arterial compliance. For the same
      decrease in mean arterial pressure, antihypertensive drugs may have differential
      effects improving arterial compliance (calcium channel blockers, converting
      enzyme inhibitors, alpha-blockers and some beta-blockers) or causing no change
      (dihydralazine, diuretics, propranolol) with resulting consequences on cardiac
      structure and function.

PMID- 8538820
TI  - Coronary blood flow and myocardial ischaemia in hypertension.
AB  - The aim of this investigation was to study the coronary pressure-flow
      relationship in 60 patients with chronic arterial hypertension of diverse
      aetiologies and in 14 normotensive subjects (control group). The hypertensive
      cohort included 6 patients with isolated systolic hypertension (ISH), 7
      renovascular hypertensive patients with abnormally elevated angiotensin II plasma
      levels but without electrocardiographic and/or echocardiographic evidence of left
      ventricular hypertrophy (LVH) and 47 subjects with essential hypertension (EH),
      21 of whom had LVH by electrocardiogram and/or echocardiogram. In the
      hypertensive cohort a Frank-Starling-like curve was found to describe the
      coronary pressure-flow relationship when the baseline values for coronary sinus
      blood flow (CBF, intravascular Doppler technique) were plotted against mean
      aortic pressure (intra-arterial blood pressure). In particular, the descending
      limb of such a curve represented a critical region where CBF was
      "inappropriately" low with respect to perfusion pressure. It was thus concluded
      that this inability of the heart to adapt CBF to its needs might account for the
      higher propensity to develop myocardial ischaemia encountered in severe essential
      hypertensive subjects with concomitant LVH and renovascular hypertensive
      patients.

PMID- 8538821
TI  - Reversibility of left ventricular hypertrophy by antihypertensive drugs.
AB  - Although the development of left ventricular hypertrophy in hypertension is
      mainly explained as a response to an increased pressure load and wall tension,
      the relation of left ventricular mass with blood pressure is usually weak, even
      when 24-hour blood pressure monitoring is used. Other factors have therefore been
      considered, such as anthropometric and demographic characteristics, differences
      in life-style, genetic influences and neurohumoral factors. Antihypertensive
      drugs differ in their effects on neurohumoral factors and it has been suggested
      that these properties may influence their potency to reduce left ventricular
      mass, mainly on the basis of open single-drug studies. Several prospective
      randomized comparative studies have however been performed to assess whether some
      (classes of) drugs are more effective than others in reducing left ventricular
      mass. A meta-analysis of such studies, comparing diuretics, beta-blockers,
      calcium antagonists and/or converting enzyme inhibitors, suggests that the
      reduction of left ventricular mass with each of these classes is similar to the
      reduction obtained with the other 3 classes statistically combined. Of particular
      interest is the observation that the 4 studies which compared a converting enzyme
      inhibitor and a calcium antagonist concluded that the effect on left ventricular
      mass was not significantly different. There is evidence, however, that drugs such
      as minoxidil and hydralazine, do not reduce left ventricular mass.

PMID- 8538822
TI  - Cerebral blood flow in untreated and treated hypertension.
AB  - Cerebral blood flow (CBF) is the same in hypertensive and normotensive man
      without neurological deficit. Chronic hypertension shifts the lower and upper
      blood pressure limits of CBF autoregulation towards higher pressure. Acute blood
      pressure reduction will lower CBF only if the pressure is taken below the lower
      limit of autoregulation. Added to this, some drugs are cerebral vasodilatators
      and have the potential for paralysing autoregulation and raising intracranial
      pressure, an effect also seen with at least some calcium antagonists. Converting
      enzyme inhibitors improve autoregulation during hypotension, probably by
      releasing angiotensin II dependent tone in the larger cerebral resistance
      vessels. With chronic antihypertensive treatment, CBF autoregulation may re-adapt
      towards normal. Converting enzyme inhibitors when given chronically probably
      retain their beneficial effect on the lower limit of autoregulation. Apart from
      this, it is uncertain whether there are chronic pharmacological effects of
      antihypertensive drugs directly on the cerebral circulation.

PMID- 8538823
TI  - Assessing vascular dementia.
AB  - Vascular dementia is the most common cause of dementia in the elderly after
      Alzheimer's disease. Many forms of vascular dementia have been described: multi
      infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy,
      cerebral amyloid angiopathy, white matter lesions associated with dementias,
      single infarct dementia, dementia linked to hypoperfusion and haemorrhagic
      dementia. The difficulty of diagnosing vascular dementia must not be
      underestimated and an international consensus is needed for epidemiological
      studies. The NINCDS-AIREN group has recently published diagnostic criteria. The
      State of California Alzheimer's Disease Diagnostic and Treatment Centers also
      proposed some which differ from the NINCDS-AIREN criteria in considering only
      ischaemic vascular dementia and not other mechanisms such as haemorrhagic or
      hypoxic lesions. Most studies stress hypertension as the most powerful risk
      factor for all forms of vascular dementia. The incidence rate ranges from 7 per
      1000 person-years in normal volunteers to 16 per 1000 person-years in
      hypertensive patients. No therapeutic attempt has influenced the course of the
      disease once the dementing condition is established. The only effective approach
      is preventive treatment. The objective of the SYST-EUR Vascular Dementia project
      is to confirm that the treatment of isolated systolic hypertension is able to
      reduce its incidence.

PMID- 8538824
TI  - Diagnosis and therapeutic aspects of stroke.
AB  - Detailed assessment of stroke is essential to distinguish haemorrhage from
      infarction, to establish the vascular territory affected and to identify patients
      with carotid stenosis or cardio-embolic disease. Computed tomography scanning
      should be routinely undertaken. Duplex Doppler sonography and echocardiography
      should be readily available but used selectively. Hypertension should not be
      treated early after ischaemic stroke. Issues requiring research include the
      optimal time to institute treatment, the degree to which blood pressure should be
      lowered in the presence of carotid stenosis and the value of antihypertensive
      treatment in normotensive survivors of stroke. Anticoagulation should be more
      widely applied in the prevention of stroke in patients with atrial fibrillation.
      Thrombolysis for acute ischaemic stroke has potential benefits and risks. It
      should be used only within randomised clinical trials, some of which may soon
      report. Endogenous glutamate causes excitotoxic damage after cerebral ischaemia.
      Many pharmacological approaches to restrict neuronal loss within the ischaemic
      penumbra are now in clinical trials. Physicians managing hypertension should take
      a lead in researching blood pressure management and neuroprotective strategies
      after acute stroke, and in directing other preventive measures such as
      anticoagulation for atrial fibrillation.

PMID- 8538825
TI  - Renal involvement in essential hypertension and treatment effects.

PMID- 8538826
TI  - Push/pull hemodiafiltration: technical aspects and clinical effectiveness.

PMID- 8538827
TI  - Acute effect of human recombinant insulin-like growth factor I on renal function
      in humans.
AB  - We examined the acute effects of insulin-like growth factor I (IGF-I) on renal
      function in 8 normal subjects who received a 3-hour intravenous infusion of IGF-I
      at a rate of 0.4 micrograms/kg.min. After starting the IGF-I infusion, the plasma
      IGF-I concentration rose quickly and achieved a plateau after 90 min that was
      threefold above the basal value. During IGF-I infusion, progressive rises in
      glomerular filtration rate (from 93 +/- 4 to 121 +/- 6 ml/173 m2.min; p < 0.01)
      and renal plasma flow (from 529 +/- 31 to 703 +/- 55 ml/1.73 m2.min; p < 0.01)
      were observed, with no change in filtration fraction. The plasma levels of
      potassium and phosphate decreased significantly during the last 90 min of the
      study, while the plasma sodium concentration remained unchanged. A significant
      decrease in the fractional excretion of sodium, potassium, and phosphate was
      observed during the last 90 min of the IGF-I infusion period. The heart rate rose
      modestly with no change in mean arterial pressure. These findings show that, when
      administered acutely, IGF-I is a potent renal vasodilator, but is
      antinatriuretic. IGF-I also enhances potassium and phosphate uptake by extrarenal
      tissues and reduces renal potassium and phosphate excretion.

PMID- 8538828
TI  - Therapeutic effect of combined treatment with monoclonal antibodies against
      intercellular adhesion molecule 1 and lymphocyte-function-associated antigen 1 in
      Masugi nephritis of WKY rats.

PMID- 8538829
TI  - Effect of erythropoietin on systolic and diastolic left ventricular function in
      chronic renal failure with anemia.

PMID- 8538830
TI  - Interaction between clonidine and cyclosporine A.

PMID- 8538831
TI  - Effect of oral prostacyclin on microclots in tube lines of a hemodialysis system.

PMID- 8538832
TI  - Cardiac hemolysis and anemia refractory to erythropoietin: on anemia in dialysis
      patients.

PMID- 8538833
TI  - McArdle's disease presenting as acute renal failure.

PMID- 8538834
TI  - Large cell lymphoma of urinary bladder presenting as acute renal failure.

PMID- 8538835
TI  - Treatment of hydrothorax complicating continuous ambulatory peritoneal dialysis.

PMID- 8538836
TI  - Are calcitriol boli worth the return to aluminum hydroxide as a phosphate binder
      in severe secondary hyperparathyroidism?

PMID- 8538837
TI  - Leg ulceration during amezinium methylsulfate therapy for hypotension in a
      hemodialyzed patient with generalized vascular calcification.

PMID- 8538838
TI  - Severe metabolic alkalosis due to choledochoduodenal fistula.

PMID- 8538839
TI  - Lethal relapse of Wegener's disease 4 years after successful kidney
      transplantation.

PMID- 8538840
TI  - Ophthalmic and central retinal artery flow velocities in hemodialysis patients.

PMID- 8538841
TI  - Sudeck's atrophy of the left tibiotarsal joint in a renal transplant patient:
      effects of medical and physical therapy.

PMID- 8538842
TI  - Release of osteocalcin fragments in the serum of dialyzed patients during
      desferrioxamine treatment.

PMID- 8538843
TI  - Nutritional profile of continuous ambulatory peritoneal dialysis patients.
AB  - Undernutrition in dialysis patients contributes to their morbidity and mortality.
      This is a cross-sectional study of the nutritional status of 61 patients treated
      with continuous ambulatory peritoneal dialysis (CAPD). They were studied with
      emphasis on assessment of their nutritional intake, anthropometric measurements,
      and evaluation of biochemical parameters. The correlation between the rate of
      CAPD peritonitis and these measurements was also examined. The majority of the
      patients (63.1%) had inadequate protein intake ( < or = 1.2 g/kg/day). A
      comparable percentage had a low energy intake ( < or = 30 kcal/kg/day). Moderate
      malnutrition, as assessed by a low triceps skinfold thickness (TST) or a reduced
      midarm muscle circumference (MAMC) of < or = 20th percentile, was detected in 52%
      and 39% of the patients, respectively. Severe malnutrition (TST or MAMC < or =
      10th percentile) was present in 36% of the patients. The serum insulin-like
      growth factor I (IGF-I) proved to be the most useful biochemical marker of
      malnutrition. It showed a positive correlation with TST (r = 0.325; p < 0.05). No
      significant correlation was observed with other short-life proteins such a
      transferrin or prealbumin. However, stepwise regression analysis showed the
      predictive value of serum IGF-I for anthropometric values to be low (adjusted R2
      = 34.6%). Wasted patients did not appear to have more infections when compared to
      their healthier counterparts. However, a weak correlation was observed between
      TST and the number of peritonitis episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538844
TI  - Effect of intraperitoneally administered agents on human peritoneal mesothelial
      cell growth.
AB  - During continuous ambulatory peritoneal dialysis, the peritoneal mesothelial cell
      layer is under continuous sloughing and regeneration processes. Agents
      unfavorable for mesothelial cell growth may be harmful to the peritoneal
      membrane. We investigated whether frequent intraperitoneally instilled agents
      affect mesothelial cell growth. Peritoneal mesothelial cells were cultured from
      the human omentum. The proliferation was assessed by using a modified
      methyltetrazolium assay and confirmed by Coulter cell counting. The results
      showed that a high-glucose medium and heparin inhibited mesothelial cell growth.
      Cephalothin at the usual intraperitoneal loading and maintenance doses is toxic
      to mesothelial cells. Ceftazidime is toxic to mesothelial cells at its loading
      dose and inhibits growth at its maintenance dose. Aminoglycosides including
      netilmicin, gentamicin, and amikacin all had inhibitory effects at the loading
      and maintenance dose ranges. Vancomycin had no effect. The usual combinations of
      heparin and cephalothin with netilmicin or gentamicin as the initial treatment
      regimen for bacterial peritonitis are toxic to mesothelial cells. These results
      suggest that some intraperitoneal agents potentially may hamper mesothelial cell
      regeneration. The judicious use of heparin and the proper choice of antibiotic
      combinations may be warranted from the point of view of peritoneal protection.

PMID- 8538845
TI  - Partial recovery of renal function in black patients with apparent end-stage
      renal failure due to primary malignant hypertension.
AB  - We report the largest series in which 12 out of 54 patients with primary
      malignant hypertension requiring dialysis recovered sufficient renal function to
      allow withdrawal of dialysis. The patients were divided into recovery (RC; n =
      12) and non-recovery (N-RC; n = 42) groups. The two groups were compared for
      variables which might predict RC. They were also assessed for survival. Nine of
      the RC and 6 of the N-RC patients presented with acute oliguria (p = 0.01). The
      initial mean arterial pressure was significantly higher in the RC than the N-RC
      group (178 +/- 17 vs. 160 +/- 27 mm Hg; p = 0.03). Although not statistically
      significant, more females recovered (8 of 12 vs. 16 of 42; p < 0.1). More
      patients presenting with serum creatinine concentrations < 1,000 mumol/l (11
      mg/dl) recovered (p = 0.09), while the presence of microangiopathic-haemolytic
      anaemia occurred more frequently in the RC (7 of 10) than in the N-RC (15 of 35)
      group (p = 0.16)> Age, kidney size, and the presence of hypertensive retinopathy
      did not distinguish between the two groups. RC patients had a greater long-term
      survival (Mantel-Cox chi2 = 4.48; p = 0.03). The renal function RC may be related
      to the type of dialysis provided (intermittent peritoneal dialysis) and to the
      use of modern potent peripheral vasodilator antihypertensive agents. Potential
      renal function RC should always be considered in patients being dialyzed for
      primary malignant hypertension.

PMID- 8538846
TI  - The role of antiphospholipid antibodies in lupus nephropathy.
AB  - Although several clinical and morphological changes observed in overt systemic
      lupus erythematosus have been associated with the presence of antiphospholipid
      antibodies (aPL), the relation between these antibodies and lupus nephropathy
      (LN) is not clear. Twenty-three patients with biopsyproved LN were
      retrospectively studied (average age 28.5 +/- 12.3 years, all women) in order to
      investigate the relationship between the presence of aPL and clinical and
      immunobiological data. The average follow-up period was 55 +/- 42 months. The
      presence of aPL (IgG and IgM) was detected at least once in all patients by ELISA
      and/or lupus anticoagulant (kaolin time). Seven patients (30.4%) were aPL+, and
      the remainder aPL-. We did not find differences related to age, period of follow
      up, blood pressure and livedo reticularis. However the prevalence of thrombosis,
      strokes and hemolysis was slightly higher in the aPL+ patients. The levels of
      antinuclear antibodies or anti-DNA antibodies, immunoglobulins and complement
      serum levels (C3, C4) were also similar in both groups. In the aPL+ group,
      proteinuria was significantly higher than in aPL- cases (2.21 +/- 1.5 and 0.91 +/
      1.07 g/24 h, respectively; p = 0.029). The renal histological pattern in both
      series was similar. However, microthrombosis in the glomerular capillary lumens
      was more frequent in the aPL+ group. The evolution of renal function was less
      favorable in aPL+ patients when compared with aPL- patients. We conclude that the
      presence of aPL in patients with LN is associated with several characteristics of
      renal impairment which may contribute to its evolution.

PMID- 8538847
TI  - Clinical profile and course and outcome of late acute rejection episodes in
      living-related-donor renal allograft recipients.
AB  - We prospectively monitored clinical data and renal function at monthly intervals
      in 165 patients who had received living-related-donor renal allografts in our
      institution between January 1981 and December 1991 and had a functioning
      allograft for 1 year or longer. During a mean follow-up period of 47.2 (range 13
      155) months, 32 patients (17.2%) developed late acute rejections, of which 14
      (43.7%) were asymptomatic. Amongst the symptomatic late acute rejections,
      worsening of hypertension was the commonest finding, being present in 11 (61.1%)
      patients, followed by oliguria in 8 (44.4%) and weight gain in 7 (38.8%)
      patients. Of these 32 late acute rejections, as many as 28 (87.5%) showed a
      response to antirejection therapy with high-dose steroids: 5 (15.6%) a complete
      response and 23 (71.9%) a partial response. The response rate was 100% if it was
      the first acute rejection (20% complete and 80% partial), 78.6% if it was the
      second (14.3% complete and 64.3% partial), and no or only a partial response to
      treatment if it was the third acute rejection episode. On long-term follow-up,
      patients who had responded to to antirejection treatment had a significantly
      better graft survival as compared with nonresponding patients: 76 and 27%,
      respectively. Our observations suggest that routine monitoring of the renal
      function at frequent intervals is essential for early diagnosis and treatment of
      acute rejections, even during the late posttransplant period. The chances of a
      response to antirejection therapy are higher during the first episode of late
      acute transplant rejection as compared with second or a third late rejection
      event.

PMID- 8538849
TI  - Hyperglycemia in diarrhea-associated hemolytic-uremic syndrome.
AB  - Hyperglycemia is a recognized complication of diarrhea-associated hemolytic
      uremic syndrome (D + HUS). Hyperglycemia developed in 8 (6.6%) of 121 patients
      with D + HUS. A literature review revealed a further 11 patients with D + HUS who
      developed hyperglycemia. The mortality rate in this group of patients is high.
      Hyperglycemia is more common in patients with D + HUS uremic syndrome who are
      female, who have an elevated white blood cell count on admission, and who develop
      anuria or a central nervous system complication.

PMID- 8538848
TI  - Reduced natriuretic effect of atrial natriuretic peptide in nephrotic syndrome: a
      possible role of decreased cyclic guanosine monophosphate.
AB  - To evaluate therapeutic and side effects, atrial natriuretic peptide (ANP) was
      administered as a pharmacological bolus dose (2 micrograms/kg body weight) to 7
      patients with nephrotic syndrome and to 13 age- and gender-matched control
      subjects. The basal glomerular filtration rate was similar, but the blood
      pressure was slightly higher in the patients than in the controls. Injection of
      ANP induced a significant increase of sodium excretion in controls (from 0.21 to
      0.52 mmol/min, medians, p < 0.01), but not in nephrotics (from 0.21 to 0.32
      mmol/min). Urinary output and free water clearance after ANP had been given were
      also lower in the patients. The natriuretic effect was mediated through
      inhibition of distal tubular fractional sodium reabsorption, as estimated by the
      lithium clearance technique, and through an increase of glomerular filtration
      rate, both effects only significant in the healthy subjects. The blood pressure
      was reduced to the same extent in the two groups. Although similar levels of ANP
      were reached in the groups after injection, cyclic guanosine monophosphate
      (GMP)/ANP was less in the patients, both basally and after ANP injection, and the
      urinary excretion of cyclic GMP did not increase in the nephrotics (from 478 to
      1,220 pmol/min, ns) as in the controls (from 389 to 2,500 pmol/min, p < 0.01).
      The urinary albumin excretion rate increased significantly in patients, whereas
      the prostaglandin E2 excretion increased after ANP administration only in
      controls. Endothelin, angiotensin II, aldosterone, and arginine vasopressin were
      unchanged in the two groups. Basal aldosterone was lower and ANP higher in
      patients than in controls. In conclusion, the natriuretic effect of ANP was
      reduced in nephrotic patients. This could not be attributed to counterregulatory
      haemodynamic or hormonal factors, but probably to reduced second messenger cyclic
      GMP.

PMID- 8538850
TI  - Severe acute renal failure: a comparison of acute continuous hemodiafiltration
      and conventional dialytic therapy.
AB  - It is unknown whether continuous renal replacement techniques result in
      diminished morbidity and mortality when compared to conventional dialytic
      techniques. To investigate this issue a previously described, retrospectively
      studied group of critically ill patients with severe acute renal failure treated
      by conventional dialysis (CD) was compared to a prospectively studied group of
      similar patients treated by acute continuous hemodiafiltration (ACHD). A combined
      retrospective and prospective clinical and laboratory investigation was carried
      out for 234 consecutive critically ill patients with severe acute renal failure
      in the intensive care unit of a tertiary institution. Biochemical, clinical and
      outcome data in all patients treated by conventional dialytic techniques
      (intermittent hemodialysis and/or peritoneal dialysis) during a 5-year period
      were retrospectively analyzed, and a prospective analysis of the same
      biochemical, clinical and outcome data in all patients treated by acute
      continuous hemodiafiltration was done over a similar time span, with statistical
      comparison of findings. One hundred and fifty patients were treated by ACHD and
      84 by CD. ACHD patients were more severely ill (mean APACHE II score: 28.2 vs.
      25.8; p < 0.01) and older (mean age: 59.9 vs. 55.5 years; p < 0.01). There were
      no significant differences in the incidence of sepsis, bacteremia and need for
      mechanical ventilation. ACHD resulted in better control of uremia (mean steady
      state plasma urea level: 20.1 vs. 31.7 mmol/l; p < 0.001) and hyperphosphatemia
      (mean serum phosphate: 1.26 vs. 1.95 mmol/l) after 24 h of initiation of therapy.
      It also allowed the administration of full nutritional support in a significantly
      greater percentage of patients (91.3 vs. 64.8%; p < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8538851
TI  - Prediction of reduction in predialysis concentrations due to interdialysis weight
      gain.
AB  - There is little quantitative information about the influence of weight change
      before and during hemodialysis on the concentration of proteins, lipoproteins,
      lipids, enzymes and other dialysis-resistant compounds in blood. We studied the
      concentration of 12 such compounds before and at the end of high-flux
      hemodialyses, 1.5 h after the start and 1, 2 and 3 h postdialysis and have
      developed formulae for roughly predicting the near steady-state 2-3 h
      postdialysis concentration. For hemoglobin, albumin, total protein and total
      cholesterol, the relationship of mean change in concentration to weight loss in
      groups was linear, and the % increase in concentration correlation correlated
      with % weight reduction (r = 0.64-0.81 and p = 0.002-0.0002). Correlations with
      ultrafiltration rate were comparable. By 3 h postdialysis values were relatively
      stable; the average fall in concentration for theses 4 compounds was 25% from end
      dialysis. The simplest formula we found which roughly predicts the % increase in
      concentration from predialysis to 3 h postdialysis is to multiply the % loss in
      body weight in kg during dialysis by 3.3. More accurate formulae were developed
      using combined and specific regression equations relating % weight loss during
      dialysis to % concentration rise. Mean values for alkaline phosphatase,
      triglycerides, lipoprotein (a), high-density lipoprotein cholesterol, calcium,
      apolipoprotein B, bilirubin and aspartate aminotransferase also rose appreciably
      during dialysis with significant increases for the first five. With major
      interdialytic weight gain, the reduction in predialysis concentrations of
      hemoglobin and cholesterol may be enough to inappropriately modify treatment
      decisions about anemia (e.g. erythropoietin) or hypercholesterolemia, and to
      cause false concern about the concentration of albumin for nutrition and
      prognosis. Major weight gain may also contribute to concentration changes in
      numerous other compounds resistant to dialysis.

PMID- 8538852
TI  - Serum secretory IgA and IgM and free secretory component in IgA nephropathy.
AB  - IgA nephropathy (IgAN) is characterized by the presence of IgA and C3 deposits in
      the mesangium. Mesangial IgA is mostly dimeric IgA1 with a J chain, lacking a
      secretory component. In view of the recent demonstration of elevated serum levels
      of secretory component and secretory IgA in liver disease and HIV infection
      associated with hyper-IgA, we measured the serum secretory component in 50 IgAN
      patients and 45 controls. Free secretory component and secretory IgA and IgM
      levels were determined by enzyme-linked immunosorbent assay. Normal or low levels
      were found patients. These data support previous work suggesting that in IgAN
      circulating and probably mesangial IgA do not originate from the epithelial
      compartment of the mucosal immunoglobulins as it is the case in other hyper-IgA
      diseases.

PMID- 8538853
TI  - Immunohistochemical quantitation for extracellular matrix proteins in rats with
      glomerulonephritis induced by monoclonal anti-Thy-1.1 antibody.
AB  - Extracellular matrix proteins (type I collagen and fibronectin) in frozen
      histologic sections of kidney cortex from rats with glomerulonephritis induced by
      a single intravenous administration of anti-Thy 1.1 antibody were quantified
      using an immunohistochemical micromethod. Type I collagen and fibronectin
      contents in renal cortex of rats with experimental glomerulonephritis (4.33 +/-
      0.79 and 10.41 +/- 2.01 microgram/mg of total protein, respectively) were 262%
      and 151%, respectively, higher than in control rats given normal mouse IgG (1.65
      +/- 0.16 and 6.88 +/- 0.95 microgram/mg, respectively; p < 0.01 in each case). In
      the glomerulonephritic rats, the increase in the contents of extracellular matrix
      proteins, especially type I collagen, correlated with increasing glomeruli with
      expansion of mesangial areas. The increase in type I collagen content correlated
      well with increasing urinary protein excretion and blood urea nitrogen and serum
      total cholesterol levels (r = 0.851, 0.812, and 0.837, respectively; p < 0.05 in
      each case). The decrease in creatinine clearance correlated with increasing
      content of type I collagen (r = 0.781; p < 0.05). The immunohistochemical
      micromethod may make it possible to evaluate the histopathological diagnosis of
      mesangial proliferative glomerulonephritis quantitatively.

PMID- 8538854
TI  - Influence of a high salt diet on glomerular injury and the preventive effects of
      amiloride in adriamycin nephropathy.
AB  - The effects of a high salt diet on glomerular hypertrophy and sclerosis were
      examined in a focal glomerular sclerosis rat model. Sprague-Dawley rats were
      injected twice with Adriamycin (ADR, 2.5 mg/kg body weight) and then divided into
      3 groups: (1) ADR rats fed a 1% sodium chloride (NaCI) diet (control ADR rats);
      (2) ADR rats fed an 8% NaC1 diet (ADR-NaC1 group), and (3) ADR rats fed a 10%
      sodium bicarbonate (NaHCO3) diet (the ADR-NaHCO3 group), and were then observed
      for 8 weeks. There were no differences in the blood pressure levels between the
      control ADR and ADR-NaC1 groups. The urinary protein excretion was significantly
      less in the ADR-NaC1 and ADR-NaHCO3 groups than in the control ADR group.
      However, a progressive increase in the blood urea nitrogen and serum creatinine
      associated with extensive glomerular sclerosis and hypertrophy was only observed
      in the ADR-NaC1 group. An increase in the glomerular diameter preceded the
      development of glomerulosclerosis in this group. Furthermore, a daily
      administration of amiloride, a Na+/H+ exchanger inhibitor, to the ADR-NaC1 rats
      prevented the development of glomerular hypertrophy and sclerosis. These results
      therefore suggest that the aggravated effect of a high salt diet on glomerular
      sclerosis may be related to glomerular hypertrophy which is associated with the
      stimulation of the Na+/H+ exchanger.

PMID- 8538855
TI  - Spontaneous arterial thrombosis associated with nephrotic syndrome: case report
      and review of the literature.
AB  - Hypercoagulability is a recognized complication of the nephrotic syndrome which
      commonly affects the venous system. Arterial thrombosis is very rare. Multiple
      factors contribute to the predisposition to thromboembolism in this condition.
      This report deals with a case of femoral artery thrombosis which responded well
      to thrombectomy and a short course of anticoagulant therapy. In spite of several
      exacerbations of his disease, our patients had no recurrence of thrombosis.
      Review of the literature reveals high rates of limb loss and recurrence of
      thrombosis. We, therefore, feel that it is important to emphasize this rare
      entity in view of the associated morbidity.

PMID- 8538856
TI  - Evidence of hepatitis C virus infection in peritoneal fluid but not in dialysate
      and ultrafiltrate or hemofiltrate.

PMID- 8538857
TI  - High prevalence of hepatitis C virus infection in hemodialysis patients from one
      dialysis unit in Slovenia.

PMID- 8538858
TI  - Characterization of alpha 2A-adrenergic receptors in GT1 neurosecretory cells.
AB  - In this paper, we report the endogenous expression of functional alpha 2
      adrenergic receptors (alpha 2-ARs) in the immortalized hypothalamic cell line,
      GT1. Membranes from GT1 cells exhibited high-affinity binding for the specific
      alpha 2-AR radioligand [3H]RX821002 (Kd = 0.2 +/- 0.03 nM, Bmax = 29.5 +/- 2.1
      fmol/mg protein, n = 3). The Ki values for the adrenergic ligands, oxymetazoline
      (1.6 +/- 0.3 nM, n = 3) and prazosin (287 +/- 89 mM, n = 3), were consistent with
      the pharmacological properties of the A subtype of alpha 2-AR (alpha 2A-AR). The
      presence of mRNA encoding the alpha 2A-AR in GT1 cell extracts was confirmed by
      Northern blot analysis. alpha 2-ARs in GT1 cells were found to be coupled to the
      inhibition of adenylyl cyclase through the pertussis toxin-sensitive class of
      heterotrimeric G-proteins. A maximal dose of the alpha 2-AR agonist UK 14304
      inhibited forskolin-stimulated cAMP production in GT1 cells by 53% (EC50 = 316
      nM). Double labeling of rodent brain sections with antibodies specific for GnRH
      and the alpha 2A-AR indicated a large proportion of neurons labeled with the GnRH
      antibody also contained alpha 2A-AR-like immunoreactivity. In both GT1 cells and
      GnRH-immunopositive neurons in brain, clusters of alpha 2A-AR-like
      immunoreactivity were associated with cell bodies and occasionally with neuritic
      processes. Punctate alpha 2A-AR-like immunoreactivity was localized to
      intracellular compartments in GT1 cells as determined by confocal microscopy.
      Whole cell radioligand binding techniques were used to show that at least one
      third of the alpha 2-AR population in GT1 cells was intracellular. In view of
      these data, GT1 cells may serve as a representative system in which to study the
      biology of alpha 2A-ARs in relation to neuronal and neurosecretory functions.

PMID- 8538859
TI  - Changes in the hypothalamic interaction between norepinephrine and prostaglandin
      E2 during sexual maturation in female rats.
AB  - The present experiments describe the study of the metabolism of 14C-arachidonic
      acid and the effect of exogenous norepinephrine (NE) on prostanoid production in
      the anterior preoptic area and medial basal hypothalamus (APOA-MBH) of
      prepubertal (16 days of age) and peripubertal female rats (30 days old). Four
      prostanoids were produced from 14C-arachidonic acid (6-keto-prostaglandin(PG)F1
      alpha, PGF2 alpha, PGE2 and thromboxane (TX)B2) and were released to the
      incubating medium. The basal percent of conversion was not significantly
      different between them. In prepubertal rats the addition of NE (10(-5) M) to the
      medium did not modify on the synthesis of these eicosanoids. In peripubertal rats
      there are no significant differences in the basal production of 6-keto-PGF1
      alpha, PGF2 alpha, PGE2 and TXB2 as compared to prepubertal rats. Moreover, the
      percentage of conversion of arachidonic acid into the different prostanoids was
      similar in prepubertal and peripubertal hypothalamus. Nevertheless, when NE (10(
      5) M) was added to the incubation medium of peripubertal hypothalamus.
      Nevertheless, significant increase in the synthesis of PGE2 was observed
      (control: 1.75 +/- 0.1; NE 2.90 +/- 0.3; p < 0.01). This increase in the
      synthesis was not accompanied by changes in the synthesis of any of the other
      three prostanoids. Prazosin, a well-known alpha 1-receptor adrenoblocker at a
      dose of 10(-5) M did not modify the production of 6-keto-PGF1 alpha, PGF2 alpha,
      PGE2 and TXB2 but did induce a complete inhibition of the stimulation by NE of
      PGE2 synthesis (NE: 2.85 +/- 0.1; prazosin: 1.9 +/- 0.09; p < 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8538860
TI  - Steroid treatment fails to induce an afternoon luteinizing hormone or prolactin
      surge in rats exposed to short-term constant light at the time of ovariectomy.
AB  - The present study investigated the effects of short-term exposure to constant
      light, initiated at the time of ovariectomy, on the ability of estradiol (E2)
      treatment alone or in conjunction with progesterone (P) to induce afternoon
      surges of LH and prolactin (PRL). Adult Fischer 344 rats, which had been
      ovariectomized (OVX) and placed into constant light (LL) on day 0, were implanted
      with Silastic capsules containing E2 on day 7 and an atrial cannula on day 8. On
      the following day (day 9), hourly blood samples were collected between 12.00 and
      20.00 h from LL-exposed animals which had received E2 treatment alone or from LL
      E2-treated animals which had also received P at 12.20 h. Blood samples from
      control animals which were OVX and treated with E2, but maintained under a 12
      hour light:12-hour dark photoperiod, were also collected. Exposure to 9 days of
      LL abolished the ability of E2 treatment to induce an afternoon surge of LH or
      PRL. The addition of P treatment to LL E2-treated animals failed to reinstate an
      LH or PRL surge. While P treatment in LL E2-treated animals induced a rise in PRL
      levels, it is unlikely, given the timing, duration, and magnitude of PRL release,
      that this enhancement was initiated by the same mechanisms which normally
      generate the afternoon surge. The results from the present study demonstrate that
      short-term exposure to LL, initiated at the time of OVX, abolishes the E2-induced
      afternoon surges of LH and PRL.

PMID- 8538861
TI  - Prenatal testosterone differentially masculinizes tonic and surge modes of
      luteinizing hormone secretion in the developing sheep.
AB  - In sheep, prenatal exposure to androgens during a critical period for sexual
      differentiation can masculinize tonic luteinizing hormone (LH) secretion and
      defeminize the LH surge. The present study investigated the possible independent
      control of these two modes of LH secretion, as revealed by their developmental
      history. Specifically, we tested the hypothesis that separate critical periods
      exist for androgenization of tonic and surge LH secretion. Pregnant ewes were
      treated weekly with testosterone cypionate (200 mg in oil). As a control and to
      induce robust masculinization of reproductive neuroendocrine function, one group
      of females received testosterone from day 30 to 86 of gestation (LONG group). To
      determine if masculinization of tonic LH secretion develops separately from that
      of the LH surge, two additional groups were treated from day 30 to 51 (EARLY
      group) or 65-86 (LATE group). At birth, the external genitalia of the LONG- and
      EARLY-treated females were masculinized; those of the LATE-treated group were
      normal. At 2 weeks of age, all androgenized females, together with normal males
      and females (n = 8 each), were gonadectomized and steroids replaced using an
      estradiol-filled Silastic capsule. First, to determine the timing of the pubertal
      decrease in steroid sensitivity, circulating LH was monitored twice weekly.
      Second, to test the function of the LH surge system, LH was measured every 1-2 h
      for 60 h after an acute increase in estradiol at 9 months of age. With regard to
      tonic LH secretion, in control males and LONG-treated females, a sustained
      increase in tonic LH in the presence of constant steroid feedback occurred at 7.1
      +/- 0.3 and 10.9 +/- 1.7 weeks of age, respectively (mean +/- SE). In control
      females, tonic LH increased at 27.1 +/- 0.8 weeks. Despite the differences in
      their genitalia, EARLY and LATE testosterone treatment produced intermediate
      effects: LH secretion increased at 19.3 +/- 1.2 and 20.4 +/- 0.8 weeks,
      respectively. In response to acute estradiol stimulation, all control females
      produced a surge of LH that peaked 18.4 +/- 0.6 h after steroid treatment. For
      the control males and LONG-treated females, LH concentrations were not sustained
      above unsuppressed pretreatment levels throughout the 60-hour sampling period.
      All but 4 of the 18 EARLY- and LATE-treated females responded to estradiol
      stimulation with a surge of LH that peaked at 29.8 +/- 1.6 and 31.8 +/- 1.3 h,
      significantly later than that of control females.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8538862
TI  - Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing
      hormone secretion.
AB  - The present studies tested the hypothesis that either short or ultrashort loop
      negative feedback regulation of gonadotropin-releasing hormone (GnRH) secretion
      occurs in the ewe. As part of ongoing studies investigating the regulation of
      follicle-stimulating-hormone secretion, we obtained the unexpected result that a
      GnRH antagonist (Nal-Glu) may stimulate GnRH secretion. In that experiment,
      hypophyseal portal blood was collected from five short-term ovariectomized ewes
      at 5-min intervals for 6 h before and 6 h after intravenous injection of Nal-Glu
      (10 micrograms/kg body weight). An increase in GnRH pulse frequency in
      association with the blockade of luteinizing hormone (LH) release was evident in
      3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH
      secretion would be more evident in an animal model in which low-frequency pulses
      of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the
      estrous cycle and six ovariectomized ewes bearing estradiol and progesterone
      implants to suppress GnRH release (artificial luteal model). In luteal-phase
      ewes, administration of Nal-Glu was followed by an increase in GnRH pulse
      frequency, pulse size and the secretion of GnRH between pulses, and by a blockade
      of LH release. In ovariectomized ewes treated with estradiol and progesterone,
      Nal-Glu administration also stimulated GnRH and inhibited LH secretion. Our
      finding that the GnRH antagonist stimulated GnRH secretion is consistent with the
      hypothesis that endogenous GnRH may influence its own release via either a short
      or ultrashort loop feedback mechanism.

PMID- 8538863
TI  - A relative depletion of luteinizing hormone-releasing hormone was observed in the
      median eminence of young but not middle-aged rats on the evening of proestrus.
AB  - Computer-assisted analysis was used to examine LHRH reaction product in the
      median eminence of young and middle-aged rats prior to and after the expected
      peak of the LH surge on proestrus. The area of LHRH reaction product was analyzed
      in 5 rostral-caudal levels (A-E) of the median eminence. The relative depletion
      of LHRH in the median eminence of young females on the evening compared to the
      afternoon of proestrus suggested LHRH neurosecretion in conjunction with the
      preovulatory LH surge. The pattern of depletion observed further suggested that
      LHRH release may occur preferentially from restricted regions of the median
      eminence or in a coordinated wave-like pattern. Four of the five levels of the
      median eminence exhibited a relative decrease in LHRH on the evening of proestrus
      in young females, and this time-related difference in LHRH reaction product was
      statistically significant in median eminence levels B and C. In contrast, little
      evidence of a relative depletion in LHRH reaction product from early to late
      proestrus was observed in the median eminence of aging animals. Moreover, the
      concentration of the densest LHRH reaction product appeared diminished in the
      median eminence of middle-aged compared to young females at the time points
      examined in the present study. The age-related differences observed in LHRH
      reaction product in the median eminence may contribute to the attenuated LH surge
      documented in middle-aged female rats. Whether these changes in LHRH
      immunoreactivity can be attributed to age-related alterations in afferents
      received by LHRH neuronal cell bodies or terminals or to intrinsic deficits in
      signalling mechanisms within LHRH neurons remains to be determined. Computer
      assisted analysis of the immunocytochemical data enabled the assessment of
      relative changes in reaction product within specific elements of LHRH neurons in
      precise regions of the median eminence.

PMID- 8538864
TI  - Acute stress suppresses the N-methyl-D-aspartate-induced luteinizing hormone
      release in the ovariectomized estrogen-primed rat.
AB  - The effects of N-methyl-D-aspartate (NMDA) and luteinizing hormone releasing
      hormone (LH-RH) on luteinizing hormone (LH) secretion were examined in
      ovariectomized estrogen-primed rats under nonstressed and acutely stressed
      conditions. The basal LH levels were significantly elevated 15 min after the
      onset of acute immobilization stress, but were not altered in emotionally
      stressed or nonstressed rats. Intravenous injections of 10 and 40 mg/kg NMDA
      significantly elevated serum LH levels by 161 and 212%, respectively, from
      baseline within 10 min in nonstressed animals. However, the NMDA-induced LH
      release was significantly reduced when tested 30 min after the onset of acute
      immobilization stress. Acute emotional stress, which did not affect the baseline
      LH, also suppressed the LH release response to NMDA, suggesting that the reduced
      LH responses to NMDA in stressed animals was not due to the elevated baseline
      level. Pituitary LH release responses to LH-RH were not affected by acute
      immobilization. We conclude from these results: (1) acute immobilization stress
      exerts both stimulatory and inhibitory effects on LH release, while acute
      emotional stress has only an inhibitory effect in estrogen-primed ovariectomized
      rats; (2) this inhibition occurs at the suprapituitary level, and (3) it involves
      a suppression of the responsiveness of the hypothalamic LH-RH neuronal system to
      the excitatory amino acid input.

PMID- 8538865
TI  - In vitro morphometric and proliferative variations in VIP-immunoreactive
      pituitary cells induced by estradiol.
AB  - Using double labelling for proliferating cell nuclear antigen (PCNA) and
      vasoactive intestinal peptide (VIP), a study was conducted to elucidate the
      repercussions of the addition of estradiol to monolayer pituitary cultures on the
      morphology, size, number, mitotic index and PCNA labelling index of VIP
      immunoreactive cells, comparing the results with those obtained in control
      cultures. The addition of estradiol (100 nM) over 3 h of incubation led to a
      significant increase (p < 0.01) in the cellular, cytoplasmic and nuclear areas of
      VIP-immunoreactive cells and in the number of these cells. The same treatment
      elicited an even greater increase in the mitotic index (p < 0.01) and PCNA
      labelling index (p < 0.01) of VIP-immunoreactive cells. The results obtained
      suggest that estrogens induce proliferation and hyperplasia of in vitro VIP
      immunoreactive pituitary cells.

PMID- 8538866
TI  - Gonadal steroid hormone regulation of proopiomelanocortin gene expression in
      arcuate neurons that innervate the medial preoptic area of the rat.
AB  - The density of beta-endorphin (beta-endo)-like immunoreactive (IR) fibers in the
      medial preoptic area (MPOA) has been shown to vary across the estrous cycle and
      is gonadal steroid hormone-dependent. These beta-endo-containing fibers are
      presumably projections of proopiomelanocortin (POMC) neurons which are located in
      the arcuate nucleus (ARC). POMC mRNA level varies across the estrous cycle in the
      ARC and its expression is differentially altered by gonadal steroid hormones.
      However, it is unclear how gonadal steroids regulate POMC gene expression in ARC
      neurons that innervate the MPOA. Therefore, combined fluorogold (FG) retrograde
      neuronal labeling and in situ hybridization histochemistry were used to
      investigate the effects of gonadal steroid hormone treatment on POMC gene
      expression in ARC neurons supplying the MPOA of ovariectomized (OVX) female rats.
      POMC-expressing cells were located in the ARC and median eminence (ME), wherein
      such neurons were significantly larger than unlabeled cells that surround them. A
      relatively greater number of ARC POMC neurons were observed to innervate the
      medial portion of the medial preoptic nucleus (MPN) than the lateral portion of
      the MPN. Estradiol (E2) and progesterone (P) treatment before FG injection did
      not affect the number of FG and POMC double-labeled neurons in the ARC, which
      suggests that hormone treatment did not alter the number of POMC-expressing
      neurons projecting to the MPN. In OVX animals, ARC POMC mRNA labeling was
      relatively low, and increased significantly in neurons of the most rostral ARC
      region 48 h after E2 treatment. P administration enhanced and prolonged the
      effect of E2 in this group of ARC neurons. E2P treatment significantly increased
      POMC mRNA expression beginning 13 h after P injection in all but the most caudal
      ARC POMC neurons. Thereafter, E2P treatment gradually increased POMC mRNA
      expression for at least 1 additional day. Gonadal steroid hormone treatment
      apparently affects POMC mRNA expression uniformly in neurons of the same ARC
      subdivision without regard to their efferent targets. Diurnal variation of POMC
      mRNA expression is present only in the most rostral ARC region, which contains a
      population of E2-sensitive POMC neurons. The results suggest that the relatively
      greater beta-endo-like IR fiber density in the medial MPN is due to a greater
      number of POMC neurons innervating this region. The pattern of innervation of the
      MPN by POMC neurons is unaffected by gonadal steroid hormone treatment, which
      appears to induce POMC expression in ARC neurons, and eventually to stimulate the
      synthesis and transport of beta-endo in POMC neuronal axons which project to the
      MPOA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8538867
TI  - Sex differences in estrogen and progesterone receptor messenger ribonucleic acid
      regulation in the brain of little striped whiptail lizards.
AB  - Sex differences in the regulation of steroid hormone receptors in brain areas
      controlling female- and male-typical sexual behavior may be important in
      determining sex differences in the display of these behaviors. This study
      examined sex differences in estrogenic effects on the relative abundance of
      messenger RNA for estrogen receptor (ER) and progesterone receptor (PR) in
      discrete brain areas of whiptail lizards, Cnemidophorus inornatus, by in situ
      hybridization with radiolabeled riboprobes. Gonadectomized females and males
      received an estradiol benzoate (EB) injection (0.5 microgram) which effectively
      induces receptive behavior in females; controls received vehicle alone. Sex and
      regional differences in estrogenic effects on ER- and PR-mRNA abundance were
      found. Females responded to EB treatment with increases in ER- and PR-mRNA
      relative abundance in the ventromedial nucleus of the hypothalamus (VMH). Males
      had similar relative mRNA abundances to females in gonadectomized controls, but
      did not exhibit increases with EB treatment. EB treatment increased ER-mRNA
      abundance in the dorsal hypothalamus of females, but not males. ER-mRNA decreases
      in the lateral septum and PR-mRNA increases in the posterior hypothalamus with
      hormone treatment were also found, but did not differ by sex. Neither sex nor
      treatment effects were definitively shown for ER- or PR-mRNA abundance in the
      anterior hypothalamus-preoptic area. The VMH controls female-typical receptive
      behavior in this species. Sex differences in the response to estrogen in this
      nucleus may therefore underlie sex differences in the display of receptive
      behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538868
TI  - The development of sexually dimorphic sensitivity to growth hormone (GH) feedback
      of the clonidine-induced GH surge in the rat.
AB  - This study investigates the development of sexually dimorphic sensitivity of the
      GH system to alpha 2-adrenergic stimulation and GH feedback in the rat.
      Sensitivity to alpha 2-adrenergic stimulation was tested with clonidine (CLN, an
      alpha 2-adrenergic agonist) which stimulates GH release in the adult male rat.
      Feedback was examined by testing whether human (h)GH suppressed the CLN-induced
      GH surge as previously demonstrated in adult male rats. The integrity of the
      pituitary and its capacity to respond to stimulation was tested at the end of the
      experiment by perifusing with GRF. Studies were conducted using a hypothalamic
      pituitary coperifusion system which allows incubation of these tissues without
      the confounding influences of peripheral hormonal and extrahypothalamic neural
      factors. Tissue from prepubertal rats of 10, 20, 25 and 30 days of age, 50-day
      old and adult rats (90-100 days) were evaluated. Results indicate that tissue
      from both male and female rats is sensitive to alpha 2-adrenergic stimulation at
      10 days of age. In male tissue, there is an increase in GH release in response to
      CLN until 30 days of age, after which a slight decline in sensitivity occurs by
      50 days of age and is maintained in adulthood. In regard to GH release from
      female tissue, a GH surge occurs in response to CLN until 30 days of age. At 50
      days and in adulthood, this response is substantially diminished. Additionally,
      there is a profound sexual dimorphism in the capacity of hGH to suppress the CLN
      induced GH surge. In tissue from male rats, by 20 days of age there is an
      apparent GH-associated inhibition of the CLN-induced GH surge which is
      significant by 25 days, is more pronounced by 30 days of age, and is maintained
      after puberty at 50 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538869
TI  - Effects of perinatal administration of haloperidol on GH pituitary contents and
      serum levels during the first postnatal month.
AB  - Perinatal dopaminergic blockade with haloperidol caused PRL increases in rat
      pituitary gland and serum which persisted during the first postnatal month.
      However the effects of dopamine on the synthesis and secretion of GH at these
      early ages are unknown. With the aim of investigating the effects of this
      blockade on postnatal GH secretion, haloperidol (1 mg/kg i.p.) was injected daily
      to pregnant rats from gestational day 16 until delivery and to pups from
      untreated mothers between postnatal days 2-6. GH pituitary contents and serum
      levels were measured weekly by RIA during the first postnatal month. The results
      showed that haloperidol induced a long-term increase in GH pituitary contents as
      well as a transient increase in serum levels. The results in serum are similar to
      those from human neonates indicating that dopamine plays a more important role as
      controller of the GH secretion in newborns than in adults.

PMID- 8538871
TI  - Current bibliographies of neuropeptides prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8538870
TI  - Inhibitory effect of amylin on growth hormone responsiveness to growth-hormone
      releasing hormone in the rat.
AB  - The effects of intracerebroventricular (i.c.v.) or intracarotid (i.a.)
      administration of amylin (AMY) on growth hormone (GH) release induced by GH
      releasing hormone (GHRH) were examined in conscious male rats. Amylin (25 ng-5
      micrograms/rat, i.c.v. or 10 micrograms/rat, i.a.) was administered 10 min before
      GHRH (2 micrograms/kg, i.a.). I.c.v. administration of AMY dose-dependently
      inhibited GH secretion induced by GHRH but when given peripherally, AMY did not
      modify the GH response to GHRH. Amylin (10(-8)-10(-6) M) had no direct effect on
      the rat anterior pituitary in vitro either alone or when incubated with GHRH. To
      characterize the mechanism(s) involved in vivo in the inhibition of GH by AMY, we
      examined, at first, the effects of AMY on GHRH-induced GH release in rats
      depleted of somatostatin by pretreatment (4 h before) with cysteamine (300 mg/kg
      s.c.). The inhibitory activity of AMY on GH secretion elicited by GHRH seems to
      be independent of hypothalamic somatostatin; in fact, AMY was still active in
      rats treated with cysteamine. In addition, we examined the effects of i.c.v. AMY
      administration on clonidine (CLO)-induced GH secretion and on dopamine and
      noradrenaline content in the brain, since it is known that GHRH is a stimulus
      sensitive to changes in central catecholaminergic activity. The failure of AMY to
      affect GH secretion induced by activation of postsynaptic alpha 2-receptors by
      CLO and the finding that the peptide decreased noradrenaline content in the
      hypothalamus and striatum, indicates that AMY may inhibit GH release by
      interfering with the facilitatory influence of the catecholaminergic system on GH
      secretion.

PMID- 8538873
TI  - The involvement of calcitonin gene-related peptide (CGRP) and substance P in
      feline pial artery diameter responses evoked by capsaicin.
AB  - The effects of capsaicin and selective neuropeptide antagonists on pial artery
      diameter were measured using an on-line image analyser in anaesthetised cats, in
      order to monitor the effects of mediators released in response to activation of
      trigeminal nerves. Perivascular injection of CGRP (10(-8) M) and the neurokinin-1
      (NK1) receptor agonist substance P methyl ester, SPOMe (10(-6) M) produced an
      increase in pial artery diameter. The vasodilatory action of these agonists was
      significantly and selectively inhibited using the CGRP receptor antagonist, CGRP8
      37 (10(-6) M), and the NK1 receptor antagonist, CP99994 (10(-6) M) respectively.
      Capsaicin (10(-8)-10(-5) M) produced a biphasic response upon perivascular
      injection that was concentration dependent. At 10(-6) M capsaicin an initial
      transient vasoconstriction was observed followed by a longer-lasting
      vasodilatation. The vasodilator component was significantly reduced by CGRP8-37
      (10(-6) M) or CP99994 (10(-6) M). These results show that chemical (capsaicin)
      activation of trigeminal nerves leads to vasodilatation of feline arteries in
      situ. This vasodilatation is mediated via the activation of CGRP and NK1
      receptors probably via the efferent release of CGRP and a substance P-like
      peptide.

PMID- 8538872
TI  - Relaxant effects of pituitary adenylate cyclase activating polypeptide (PACAP) on
      epithelium-intact and -denuded guinea-pig trachea: a comparison with vasoactive
      intestinal peptide (VIP).
AB  - The effect of pituitary adenylate cyclase activating peptide (PACAP 1-27) was
      examined on epithelium-intact and -denuded guinea-pig tracheal strips (GPT) and
      compared to vasoactive intestinal peptide (VIP) and salbutamol. PACAP (10(-11)
      10(-8) moles) induced dose-dependent relaxations of the basal tone of both
      epithelium-intact and -denuded GPT. PACAP was approximately three times less
      potent than either VIP or salbutamol in relaxing epithelium-intact GPT. The
      relaxant effects of both peptides and salbutamol were markedly attenuated
      following removal of the epithelial layer. L-NAME (10(-4) M), a nitric oxide
      synthase inhibitor, did not affect the responses induced by either PACAP or VIP
      demonstrating that the relaxant effect is independent of nitric oxide synthesis.
      Phosphoramidon (5 x 10(-6) M) potentiated the relaxant responses of epithelium
      intact GPT to both PACAP and VIP but did not affect the responses of epithelium
      denuded GPT. PACAP and VIP also induced relaxations of the guinea-pig upper
      bronchus. In addition, PACAP (10(-6) M), as well as VIP, significantly inhibited
      the release of TxB2 induced by LTD4 (10(-7) M) from chopped guinea-pig lung
      suggesting that this newly isolated peptide, which has 68% homology with VIP, may
      possess anti-inflammatory action in the lung.

PMID- 8538874
TI  - Metabolism of galanin and galanin (1-16) in isolated cerebrospinal fluid and
      spinal cord membranes from rat.
AB  - The occurrence of galanin (GAL) in the spinal cord and reports suggesting that it
      acts as an endogenous inhibitory spinal modulator in sensory/noxious
      transmission, have focused interest on its metabolism in the spinal cord. The
      metabolic half-lives and degradation patterns of GAL(1-29) and the high affinity
      N-terminal fragment GAL(1-16), were determined in isolated cerebrospinal fluid
      (CSF) from rats, and analysed by reverse phase HPLC. The half-lives for GAL(1-29)
      and GAL(1-16) in isolated rat CSF at 37 degrees C were 120 min and 60 min,
      respectively. The first degradation products which we could isolate and identify
      of GAL(1-16) were: GAL(3-16) and GAL(3-12) and for GAL(1-29): GAL(1-5) and GAL(1
      4), all without affinity to spinal galanin receptors. Degradation studies of
      GAL(1-29) and GAL(1-16) in a spinal cord membrane preparation, in absence or
      presence of different protease inhibitors: E-64, pepstatin A, 3,4-DCI, bestatin,
      phosphoramidon, kelatorphan and thiorphan, or metal chelators: EDTA, EGTA and o
      phenanthrolin, suggest that a phosphoramidon sensitive zinc-metalloprotease is
      mainly responsible for the degradation of GAL(1-29) and GAL(1-16), since both o
      phenanthrolin (0.3 mM) and phosphoramidon (920 microM) substantially prolong
      their half-lives.

PMID- 8538875
TI  - C-type natriuretic peptide can modify the acute and chronic effects of morphine.
AB  - Different doses (0.2-200 ng) of C-type natriuretic peptide (CNP) were
      administered into the lateral brain ventricle, and morphine (5 mg/kg) was
      injected subcutaneously. The analgesic effect was measured in a tail-flick test,
      in CFLP mice. CNP administered centrally did not itself affect pain sensitivity,
      but it depressed the acute antinociceptive effect of morphine 30 min after icv
      (0.2, 2 or 20 ng) CNP administration and the 2 and 20 ng doses also decreased
      this action after 60 min. CNP in a 0.2 or 200 ng dose blocked the development of
      acute tolerance to morphine after 30 min, as did the 200 ng dose at 60 min. CNP
      in a 0.2 ng dose blocked the development of chronic tolerance to morphine after
      30 min, but there was no effect at 60 min. Morphine withdrawal signs were studied
      by injecting naloxone (1 mg/kg sc). There was no significant difference in
      symptoms between the tolerant group and the animals treated with CNP.

PMID- 8538876
TI  - In vivo effects of lamprey GnRH-I and cyclized analogs: a structure-activity
      study.
AB  - Lamprey GnRH-I and lamprey GnRH-III are the only two members of the GnRH family
      to have substitutions in the sixth position, Glu6 and Asp6, respectively; all
      other GnRH peptides have Gly in the sixth position suggesting a different
      conformational structure. Thus, a structure-activity study of lamprey GnRH-I or
      analogs that were cyclized or with sixth position substitutions were determined
      in vivo in adult female sea lamprey, Petromyzon marinus. The following analogs
      which were tested, ([D-Glu6]-GnRH-I; cyclo-[D-Glu6-Trp7-Lys8]-GnRH-I; or cyclo
      [Glu6-Trp7-Lys8]-GnRH-I), significantly elevated plasma estradiol compared to
      controls. However, [D-Glu6]-lamprey GnRH-I was the only analog to significantly
      stimulate ovulation while another analog [Gly6]-lamprey GnRH-I significantly
      delayed ovulation. These data suggest that the sixth position of lamprey GnRH is
      critical for function.

PMID- 8538877
TI  - Increases in cortical neuropeptide Y and somatostatin concentrations following
      haloperidol-depot treatment in rats.
AB  - The concentrations of neuropeptide Y (NPY) and somatostatin (SS) have been said
      to be altered in the brain and cerebrospinal fluid of schizophrenic patients.
      This alteration could result from the neuroleptic treatment. Therefore, it is of
      interest to evaluate effects of long-term treatment with neuroleptics on the
      peptide concentrations in the brain. Haloperidol (HPD) is one of the most
      frequently used neuroleptics for the treatment of schizophrenia. We determined
      regional brain levels of NPY and SS following HPD administration in the rat. A
      single intraperitoneal injection of HPD, at a dose of 1 mg/kg, did not affect
      peptide levels in the brain regions studied. Four weeks after an intramuscular
      deposit injection of HPD decanoate, 50 mg/kg, NPY concentrations were increased
      in a number of areas of the cerebral cortex. SS content was also significantly
      increased in the lateral prefrontal cortex and anterior cingulate cortex. Both
      peptide levels were decreased in the striatum. These results suggest that the
      reduction found in these peptides' levels in the cerebral cortex of the brain
      from schizophrenic patients may not be the consequence of HPD treatment and that
      these peptides' levels might be increased in the cerebral cortex of the brain of
      schizophrenic patients following the treatment with HPD.

PMID- 8538878
TI  - Penicillin-G induced interictal activity increases both opioid peptide tissue
      content and in vitro release in the rat brain.
AB  - Penicillin-G has been used as a common agent to produce epileptic foci and
      interictal activity. The development of the interictal spikes has been associated
      with enhanced inhibitory effects. There is evidence that the opioid peptides play
      an important role in the production of some transient postictal behaviors. In
      order to test whether enkephalins are involved during the interictal activity, we
      analyzed immunoreactive met- and leu-enkephalin content and their release in
      vitro, after the injection of 50 IU of penicillin-G into the left amygdala. Male
      Wistar rats were injected once daily for 5 days, and sacrificed by decapitation
      (15 min after the penicillin-G infusion) on the fifth day. The rats were divided
      into two groups: 1. In one group we analyzed the tissue content of enkephalins in
      hypothalamus, hippocampus, amygdala, striatum and cerebral cortext. 2. The second
      group was used for the assessment of the in vitro release of enkephalins from
      amygdala slices. In the amygdala, the drug treatment produced an increase in the
      tissue content of IR-ME. No changes occurred in the other structures. The content
      of IR-Leu-enkephalin increased in all structures analyzed except the cerebral
      cortex. In vitro release of both enkephalins increased in drug treated animals.
      These results suggest that the enkephalins could be involved in postictal
      mechanisms, as a result of repetitive interictal spiking.

PMID- 8538879
TI  - The effects of repeated amphetamine administration on the thyrotropin-releasing
      hormone level. Its release and receptors in the rat brain.
AB  - The effects of single and repeated administration of amphetamine (5 mg/kg, i.p.,
      twice a day for 14 days) on the thyrotropin-releasing hormone (TRH) level,
      release and receptors in the rat striatum and nucleus accumbens were evaluated.
      Both treatments decreased the TRH level in those structures at 2 h after the drug
      injection. These effects were accompanied with elevation of the basal release of
      TRH from the nucleus accumbens and striatal slices at the same time point,
      whereas the stimulated (K+, 56 mM) TRH release was attenuated following repeated
      amphetamine administration. Acute amphetamine had no effect on the density and
      affinity of TRH receptors. Repeated amphetamine increased the Bmax of TRH
      receptors in the striatum (by ca 49%) and nucleus accumbens (by ca 38%) at 2 h
      after the last drug injection. At 72 h after the last amphetamine administration,
      the Bmax of the TRH receptor in the striatum was still elevated (by ca 42%),
      whereas in the nucleus accumbens it returned to control level. No changes in the
      affinity of TRH receptors following repeated amphetamine were found. The obtained
      results indicate that repeated amphetamine evokes long- and short-term up
      regulation of TRH receptors in the rat striatum and nucleus accumbens,
      respectively. Furthermore, it is suggested that these changes may be an adaptive
      response to the amphetamine-induced alterations in the TRH tissue level and
      release.

PMID- 8538880
TI  - Aged rats are still responsive to the antidepressant and memory-improving effects
      of oxytocin.
AB  - Oxytocin, intraperitoneally injected to 26-month-old male rats 60 min before
      testing, significantly improved social memory (at doses of 3 and 6 ng/kg) and
      reduced the duration of immobility in the behavioral despair test (at doses of 50
      and 500 micrograms/kg). These results are in agreement with previous data
      obtained in adult rats and indicate that aging does not compromise the social
      memory improving and antidepressant-like activities of oxytocin.

PMID- 8538881
TI  - Central pain: diagnosis and treatment strategies.
AB  - The pathophysiology of central pain (CP) remains poorly understood. The paucity
      of objective findings on clinical examination of some of these patients can add
      to the difficulty in establishing a concrete diagnosis of CP. A pathophysiologic
      conceptual framework has been established to provide guidance. The goal of
      treatment should be pain reduction rather than complete pain relief. Surgical
      procedures have been used for specific causes of CP, but no one surgical
      technique helps relieve pain over the long term in all CP patients. Likewise, no
      one pharmacologic agent is successful in all CP patients, and pain relief is
      often incomplete. Pharmacologic treatment may take the form of stepwise addition
      of various agents, the cornerstone of which are antidepressants, followed by
      anticonvulsants, opioids, and other drugs. If all standard pharmacologic
      treatments fail, treatment of psychological problems induced by chronic pain is
      necessary since depression and the risk of suicide are significant in patients
      with poorly controlled CP.

PMID- 8538882
TI  - Neuropathic pain of peripheral origin: advances in pharmacologic treatment.
AB  - A variety of mechanisms may generate pain resulting from injury to the peripheral
      nervous system. None of these mechanisms is disease-specific, and several
      different pain mechanisms may be simultaneously present in any one patient,
      independent of diagnosis. Diagnosis of neuropathic pain is often easily made from
      information gathered on neurologic examination and from patient history. Evidence
      of sensory disturbances elicited on examination combined with laboratory tests
      confirming injury to peripheral nerve establishes the diagnosis of neuropathic
      pain. Although treatment of neuropathic pain may be difficult, optimum treatment
      can be achieved if the neurologist has a complete understanding of the
      therapeutic options, the mainstay of which is pharmacotherapy. Selection of an
      appropriate pharmacologic agent is by trial and error since individual responses
      to different agents, doses, and serum levels are highly variable. An adequate
      trial for each agent tried is key to pharmacologic treatment of neuropathic pain.
      Tricyclic antidepressants are first-line agents, although other drugs, including
      anticonvulsants, local anesthetic antiarrhythmics, clonidine, opioids, and
      certain topical agents, also offer pain relief in some patient populations. The
      novel antidepressants venlafaxine and nefazodone are potentially useful new drugs
      that are better tolerated than tricyclic antidepressants.

PMID- 8538883
TI  - Psychiatric aspects of chronic pain.
AB  - Chronic pain complaints often reflect or are influenced by psychiatric factors.
      Physicians commonly encounter "illness-affirming behaviors" in which patient
      complaints or symptoms go beyond what should be expected from a specific disease
      process. In this paper, I describe common psychiatric conditions that often
      feature pain as part of the illness: somatization disorder, hypochondriasis,
      factitious physical disorders, pain associated with psychological factors (new
      DSM-IV nomenclature), and malingering. These conditions can be distinguished
      based on the conscious awareness (or lack of awareness) of both motivation and
      symptom production. Other psychiatric disorders may strongly influence chronic
      pain without directly causing it--depression, anxiety, panic, and post-traumatic
      stress disorders. Except for malingering and factitious pain, chronic pain should
      be regarded as genuine. Effective management requires psychiatric as well as
      biological considerations.

PMID- 8538884
TI  - Chronic pain: from theory to practical management.
AB  - The neurologist is an important part of the pain management team. Factors that
      can alter presentation and complicate establishing a diagnosis are reviewed. A
      multidisciplinary approach to evaluation is advocated, particularly the inclusion
      of independent psychiatric or psychological evaluation. Treatment planning
      consists of addressing potential sources of failure of pain management, setting
      appropriate goals, and using the diagnostic assessment to plan pharmacologic and
      nonpharmacologic interventions based on pain mechanisms. Even if pharmacologic
      interventions do not alter pain, an education-oriented behavioral pain program
      integrated with physical therapy can improve function and foster self-reliance in
      controlling pain.

PMID- 8538885
TI  - Commissary tobacco sales: the elimination of a historic artifact.

PMID- 8538886
TI  - Good Lord, deliver us.

PMID- 8538887
TI  - Biological warfare in the twentieth century: lessons from the past, challenges
      for the future.
AB  - Biological warfare and fear of biological warfare have affected our wars, our
      peace, and our research throughout this century. During World War I, animals were
      deliberately infected with glanders. During World War II, biowarfare research was
      carried out by Japan, Germany, England, and the United States. Japan carried out
      biological warfare attacks in China. England used biological warfare for the
      assassination of Reinhard Heydrich. In the 1950s and 1960s, Army researchers
      released bacteria over U.S. cities in biological warfare tests. The most frequent
      biological warfare terrorist episodes have been contamination of food and water.
      Although biological warfare can be very low tech, genetic engineering is capable
      of making biowarfare agents available in vast quantities. Biowarfare research
      should continue, but the National Institutes of Health should oversee human
      biological warfare research.

PMID- 8538888
TI  - A study of the efficacy of nonoperative treatment of presumed traumatic
      spondylolysis in a young patient population.
AB  - The purpose of this study is to report the results of nonoperative treatment of
      presumed traumatic spondylolysis in a young patient population seen at the Walter
      Reed Army Medical Center Orthopaedic Surgery Spine Service from 1986 to 1994. A
      retrospective chart review analysis with recent follow-up was performed on 29
      patients diagnosed through clinical examination and plain radiographs. Bone scan
      was reserved for those patients with an examination consistent with spondylolysis
      yet inconclusive plain films. All patients were treated with activity
      modification (to include a temporary profile for active duty military), full-time
      bracing (most commonly a thoracolumbosacral orthosis), and nonsteroidal anti
      inflammatory drugs. Narcotic analgesics were added to this regimen, if indicated.
      There were 23 males and 6 females with an average age of 21 (range 13-31). There
      were 7 United States Military Academy cadets, 7 dependent children, 5
      noncommissioned officers, 6 enlisted, and 4 officers. Of the 29 patients with
      spondylolysis, 20 had an L5 defect, 6 had an L4 defect, 4 had an L3 defect, and 1
      had an L2 defect. Two of the 29 patients healed their spondylolysis, but the
      remainder failed nonoperative treatment. In the population of patients referred
      to our institution, spondylolysis is not a benign process. The literature
      suggests that the majority of these injuries heal, yet this has not been our
      experience. We propose that if the patient is diagnosed acutely with a fracture
      of the pars interarticularis and the aforementioned proven regimen is initiated,
      the chances for a successful nonoperative outcome are optimized.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8538889
TI  - Dental emergency visits of Marine Corps personnel.
AB  - The purpose of this study was to determine the incidence and distribution of
      dental emergencies in Marine Corps personnel. Dental emergencies were recorded
      from June 1989 to June 1990 for personnel who were in garrison, deployed, or
      participating in field exercises. A standardized data-collection form was
      distributed to participating Marine Corps dental clinics and to dental officers
      assigned to Marine Corps deployments or field exercises. A total of 890 dental
      emergency visits by Marines were recorded: 699 for Marines while in garrison, 136
      while deployed, and 55 while participating in field exercises. Tooth/restoration
      fracture without pulpal involvement and pericoronitis were the most frequent
      diagnoses at emergency visits in each of the three environments. The mean
      incidence rate of dental emergencies per 1,000 person-years for deployed Marine
      Corps personnel was 57.2.

PMID- 8538890
TI  - Women as prisoners of war.
AB  - American women are increasingly becoming involved in combat-related roles.
      Inevitably, our country will have several killed and taken prisoner. No National
      Academy of Science/National Research Council or VA study has ever been undertaken
      to examine the chronic sequelae of the experiences undergone by these captured
      women. This paper examines the after-effects of 3.5 years of incarceration on the
      79 American women taken prisoner by the Japanese in the Philippines during World
      War II. Emphasis is given to their living conditions in a prisoner-of-war camp
      and their resulting long-term disabilities. Comparison of data reported in this
      paper with those of several epidemiological studies of male survivors of
      Philippine camps allows several novel points to be made. Overall, half of the
      women had a service-connected disability, exactly like the men. Furthermore,
      although the average degree of service-connected disability, 37%, is the same as
      that of the men, not one of the women in this study was service-connected for
      tuberculosis or peptic ulcer disease. This is a major finding, since, compared to
      age-matched combat controls, the men had a higher post-repatriation death rate
      for the first 7 years due to tuberculosis; likewise, peptic ulcer disease is so
      common in the male survivors that it is a presumptive service-connected
      disability.

PMID- 8538891
TI  - Impact of pharmacist counseling on medication knowledge and compliance.
AB  - The impact of discharge counseling was measured in a veteran patient population
      in a large tertiary-care government medical center. Upon discharge, seventy
      patients were randomly assigned to one of two groups: one group received verbal
      medication counseling from a pharmacist, the other group did not. Medication
      knowledge and compliance were assessed by interviewing each patient approximately
      6 weeks after discharge. Sixty patients (31 counseled, 29 uncounseled) completed
      the study. Forty-five patients were from our rehabilitation division (housing
      psychiatric, intermediate, and long-term care patients), and 15 patients were
      from our acute-care division. Overall, counseled patients were no more
      knowledgeable or compliant than uncounseled patients. However, among those
      patients discharged from our acute-care division, counseled patients were more
      knowledgeable and compliant than uncounseled patients. In all patients,
      medication knowledge and compliance decreased as their number of medications
      increased. Our discharge counseling program had little impact when examining all
      study patients. But in acute-care patients, discharge counseling did increase
      both medication knowledge and compliance. Our study also showed that, in both
      counseled and uncounseled patients, medication knowledge and compliance decreased
      as the number of discharge medications increased, and additional pharmacist
      counseling would likely prove beneficial to those patients discharged on multiple
      medications.

PMID- 8538892
TI  - Family practice management in an overseas theater.
AB  - The mandate to convert outpatient primary care programs to family practice
      programs reached the overseas military theater a number of years ago. Everyone
      seemed positive about initiating a system that facilitated the relationship
      between the patient and the health care professional of his/her choice. As a
      consequence, many new programs were started. A number of concerns have been
      raised by local medical treatment facility commanders. These concerns demonstrate
      uncertainty regarding the goals, principles, and expectations of family practice
      programs. This article endeavors to bring helpful information regarding the
      philosophy and strengths of family practice. Two very different patterns of
      organizational structure are discussed and practical advice is given that will,
      it is hoped, be helpful to senior clinical managers.

PMID- 8538893
TI  - Prescribed medication use among troops deploying to Somalia:
      pharmacoepidemiologic analysis.
AB  - To describe the frequency of chronic ambulatory prescriptions dispensed to
      troops, pharmacists analyzed records of soldiers deploying to Somalia for
      Operation Restore Hope. Prescriptions recorded in the Fort Drum pharmacy data
      base for soldiers deploying between November 24, 1992, and January 12, 1993, were
      compared to the roster of troops deployed. Among 3,701 deploying soldiers, 273
      patients (7.4%) received 425 prescriptions. For each 1,000 troops, 114.8
      prescriptions were dispensed. Of 333 presumptive diagnoses, the most common
      diagnostic groups were contraceptive, musculoskeletal, dermatologic, respiratory,
      and cardiovascular. Of 425 prescriptions, the most common therapeutic classes of
      medication dispensed were oral contraceptives, anti-inflammatory drugs, acne
      treatments, and beta-adrenergic agonists. Generically, the common prescribed
      substances were contraceptives, ibuprofen, pirbuterol, temazepam, piroxicam, and
      beclomethasone. Although women represented 6.8% of troops, women represented
      31.5% of prescription recipients and received 29.4% of prescriptions. Women were
      6.5 times as likely to receive a prescription as men (p < 0.0001); this relative
      risk was 3.4 if contraceptives were omitted from analysis (p < 0.0001). Two
      hospitalizations in Somalia may have been related to medication use.

PMID- 8538894
TI  - Abnormal cervical smears in the military recruit population.
AB  - Human papillomavirus is a common genital tract infection believed to be a
      causative agent of uterine cervical dysplasia. In a minority of cases, dysplasia
      progresses to squamous cell carcinoma. We reviewed the cervical smear reports for
      all female recruits who reported for training at Navy Recruit Training Center,
      Orlando, in calendar year 1993. During this period, 8,029 female recruits
      reported for training. We found that 24 recruits (0.30%) had a finding of high
      grade squamous intra-epithelial lesion (HSIL); 203 (2.5%) had a finding of low
      grade squamous intraepithelial lesion (LSIL); 377 (4.7%) had abnormalities other
      than HSIL or LSIL; and 7,425 (92%) had no abnormalities. These prevalence rates
      are lower than those reported for other populations.

PMID- 8538895
TI  - Comparison of rectal to intranasal administration of midazolam for premedication
      of children.
AB  - Sixty children aged 3 to 9, undergoing minor surgical procedures, were studied to
      compare 0.5 mg/kg intranasal with 0.5 mg/kg rectal midazolam as a premedication.
      The children were evaluated for their ability to tolerate the medication,
      preanesthetic sedation, and alertness after anesthesia. Both premedication routes
      were equally effective in sedating the children. In both groups, a significant
      loss of effectiveness was noted if induction of the anesthesia began more than 30
      minutes after administration of the medication (p < 0.0003). Rectal midazolam was
      much better tolerated by the children than the intranasal route (30 versus 3, p <
      0.0001). We advocate the rectal over the intranasal route for premedication with
      midazolam in children, and anesthetic induction should occur no more than 30
      minutes after administration of premedication.

PMID- 8538896
TI  - Stress and arousal in deployment of a combat support hospital.
AB  - Two hundred thirty-nine soldiers from the 28th Combat Support Hospital were
      evaluated for stress and arousal during deployment preparations for Operation
      Uphold Democracy. We measured stress and arousal using the Stress Arousal
      Checklist and found increased levels of arousal in officers and older soldiers.
      We also found higher levels of arousal in soldiers reporting a greater number of
      hours of sleep during the preceding 24 hours. We found no significant difference
      in stress scores for several demographic and coping behavior groups. Based on
      lower arousal scores, younger, sleep-deprived, and enlisted soldiers may be at
      the highest risk for accidents during deployment preparations.

PMID- 8538897
TI  - Reflections on a humanitarian mission 20 years later: Operation Babylift.
AB  - Humanitarian missions command a dominant share of military operations in the
      current world situation. It is imperative that the lessons learned from such
      missions include the personal and personnel costs of such missions if those
      individuals who will participate in such operations are to be prepared for the
      uncertainties and the emotional pain entailed in these missions. Sharing a
      personal experience of participation in one such mission--Operation Babylift--can
      provide an avenue for learning about the costs of such missions and indicating
      ways in which individuals can prepare themselves before actually participating in
      such missions.

PMID- 8538898
TI  - Work of the Slavonski Brod General Hospital during the war in Croatia and Bosnia
      and Herzegovina in 1991-1992.
AB  - Between September 1, 1991, and December 31, 1992, 7,043 wounded persons, 4,566 of
      them heavily wounded, were treated at the Slavonski Brod General Hospital. There
      were three characteristic periods in the work of the hospital during the war.
      Until March 31, 1992, the hospital provided care for the wounded from the east-
      and west-Slavonian fronts, at the level of the fourth echelon. The second period
      started with war actions in Bosanska Posavina and Bosnia and Herzegovina, when
      the Slavonski Brod General Hospital was the only place offering appropriate care
      to the wounded from the area. During that period, surgical professions and, to a
      limited extent, conservative professions were working at the hospital. The third
      period began with the fall of Bosanska Posavina, toward the end of October 1992,
      and lasted until the end of the year. During that period, the number of the
      wounded and previously surgically treated at the Tolisa War Hospital, in the
      unoccupied area of Bosnia and Herzegovina, admitted to the Slavonski Brod General
      Hospital, decreased. The total mortality rate in the treated subjects was 2.66%,
      whereas during the war in Bosanska Posavina it was 3.0%. Throughout the war,
      there was no interruption in the work of hospital conservative professions,
      although the extent of their work was reduced.

PMID- 8538899
TI  - Air evacuation of critically burned patients.
AB  - We analyze the repercussions of air evacuation on the physiopathology of the
      critically burned patient based on the experience on 63 patients evacuated by
      air. Clinical repercussions are due to accelerations, vibrations, noise, and,
      primarily, to altitude. Accelerations are important during take-off and landing,
      and vibrations may be important in helicopter evacuations in the presence of
      craniofacial trauma. The noise, especially in helicopters, can interfere with
      diagnostic and therapeutic maneuvers in-flight. The altitude modifies atmospheric
      pressure, partial pressure of oxygen, and water concentration in inhaled air. In
      the aircraft we use, atmospheric pressure is between 550 and 532 mm Hg at the
      normal flight altitudes. This situation determines the expansion of body gases.
      Hypoxia seriously worsens any respiratory insufficiency, primarily in the
      presence of smoke inhalation. The decrease of water concentration in the inhaled
      air compels the increase of fluid perfusion. Pre-flight and in-flight measures
      are analyzed, especially with regard to smoke inhalation, pneumothorax, and
      parenteral perfusion.

PMID- 8538900
TI  - Occult inguinal hernia, a cause of rapid onset of penile and scrotal edema in
      patients on chronic peritoneal dialysis.
AB  - From 1976 to 1993 we inserted 160 chronic peritoneal dialysis catheters for renal
      failure patients. Three of these patients developed sudden onset of penile and
      scrotal edema after the catheter had been in place for several months. The first
      patient was diagnosed by instilling technetium sulfur colloid in the peritoneal
      cavity, which showed the radioisotope flowing via the right inguinal canal. He
      was operated on and the processus vaginalis was tied off and the scrotal and
      penile edema resolved. Subsequently, two more patients were seen with similar
      problems and had their inguinal canals explored and the processus vaginalis in
      one and the hernia sac in the other were found and tied off, which resulted in
      resolution of the problem. This is an uncommon complication, reported to occur in
      3 to 4% of patients.

PMID- 8538901
TI  - Pathological study of implanted dacron grafts in surgery of thoracic aortic
      aneurysms.
AB  - We studied woven dacron grafts that had been implanted in 5 patients of thoracic
      aortic aneurysms. In addition to usual stains, immunocytochemical analysis was
      performed using monoclonal antibodies to the muscle actin (HHF35) and to the
      macrophage (HAM56). In the graft of 5 and 24 days implantation, thin thrombi
      containing red cells and fibrin covered the luminal surface in some places, and
      macrophages came into the thrombi. In the grafts of 12 and 38 months
      implantation, intimal hyperplasia of 0.2-1.0 mm thickness was seen at the
      anastomotic segments with the accumulation of smooth muscle cells. Except for the
      anastomotic segments, connective tissue matrix with collagen fibers covered the
      luminal surface, and in some hollows of the graft crimps, old and fresh thombi
      were seen in layers. Organizing thrombi of 1.0 mm thickness attached where the
      branched graft was anastomosed to the main graft. Anastomotic intimal hyperplasia
      in the graft of 148 month implantation was 0.4-1.0 mm in thickness and 5-10 mm in
      length, and aside from the intimal hyperplasia, an endothelial lining did not
      cover the luminal surface of the graft. In the thoracic aorta, woven dacron graft
      implantation did not cause a critical stenosis with the intimal hyperplasia. The
      mural thrombi formed at the branched graft, however, threatened to result in
      graft occlusion or embolization.

PMID- 8538902
TI  - Myocardial revascularization using both attached internal thoracic arteries. Mid
      term clinical evaluation of 117 cases.
AB  - The current trend in myocardial revascularization is to use arterial grafts in
      most, if not all cases. The right internal thoracic artery was a logical choice
      once the left internal thoracic artery patency on the LAD was known. This study
      presents our experience of using both attached internal thoracic arteries (ITA).
      Between January and October 1990, 159 myocardial revascularizations were
      performed in our department. In 117 cases, bilateral ITA grafting was used with
      non exclusion criteria. There were 100 male and 17 female patients, with a mean
      age of 61 +/- 8. The LITA was anastomosed to the LAD in 44 cases, and to the
      marginal artery in 74. The RITA was anastomosed to the LAD in 68 cases, to the
      marginal artery in 47 and to the right coronary artery in 2. An average of 3.5
      bypasses per patient, including saphenous vein grafts, were performed. Six
      patients (5%) died within 30 days. Four patients (3.4%) were diagnosed as having
      periperative myocardial infarcts. There were no reoperations for bleeding. One
      patient (0.9%) presented a sternal wound infection. Mean follow-up was 18 +/- 7
      months. Six patients died during the follow-up and the survival rate was 91%.
      Ninety-five patients (91%) were symptom-free, 9 patients had a recurrent angina.
      Postoperative coronary angiography was performed in 11 patients (10%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8538903
TI  - [Variations in microalbuminuria in essential hypertension treated with ACE
      inhibitors, calcium antagonists and their association].
AB  - OBJECTIVE: Microalbuminuria is an early and sensible marker of renal impairment;
      furthermore, many authors consider it an independent predictive index for
      cardiovascular morbidity and mortality. In our study we observed this parameter
      in hypertensive patients treated respectively with ACE-inhibitors, calcium
      channel blockers and their combination. EXPERIMENTAL DESIGN: Open comparative
      trial, 6 months follow-up. ENVIRONMENT: Outpatients, with no changes from usual
      lifestyle; office measurements. PATIENTS: Forty patients (22 men and 18 women)
      aged 52-78 years, with essential hypertension and microalbuminuria; diabetics and
      subjects with renal impairment were excluded. TREATMENT: Chronic antihypertensive
      drug therapy, respectively with nitrendipine 20 mg/die (Group A, n = 10),
      lisinopril 20 mg/die (Group B, n = 20), and lisinopril 20 mg/die+nitrendipine 20
      mg/die (Group C, n = 10); all drugs were administered orally. MEASUREMENTS:
      Detection of urinary albumin excretion with immunochemical method (Micral Test);
      urine samples were taken immediately after arousal for three consecutive days;
      office blood pressure monitoring (sitting and standing) during the same day, with
      at least 2 separate readings. RESULTS: Out of 34 patients examined at follow-up,
      (8 from Group A, 17 from Group B and 9 from Group C) urinary albumin excretion
      rates were as follows: Group A: reduction (but not disappearance) in 3 patients
      (37%), no change in 4 patients (50%), increase in 1 patient (13%); Group B:
      disappearance in 11 patients (65%), reduction in 3 patients (17.5%), no changes
      in 3 patients (17.5%); Group C: reduction (but not disappearance) in 5 patients
      (55.5%), no changes in 4 patients (44.5%). CONCLUSIONS: In hypertensive patients
      not diabetics and not renally impaired with microalbuminuria, ACE-inhibitors
      appear to be a move suitable drug therapy than calcium channel blockers or the
      combination ACE-inhibitor+calcium channel blocker.

PMID- 8538904
TI  - [Quality of life in patients undergoing mitral valve substitution].
AB  - AIM: The aim of the present study was to evaluate the quality of life after
      mitral valve replacement through the analysis of behavioural, psychological,
      functional, economic and working changes, as well as alterations in social and
      sexual life after surgery. SETTING: The study was performed before and after
      surgery in a cardiological ward. POPULATION: The population studied included 206
      patients undergoing mitral valve replacement surgery. Results were compared with
      a control population of patients suffering from mitral valve disease and
      receiving medical therapy. METHOD: All patients were asked by medical staff to
      compile a series of five self-evaluation questionnaires: General Well-Being
      Schedule, Physical Symptoms Distress Index B, Social Participation, Sexual
      Satisfaction Unified Test and Work Performance and Satisfaction. RESULTS: Our
      results showed a significant improvement in the perception of quality of life
      after mitral valve replacement. In particular, the state of general well-being
      improved significantly with a clear reduction in symptoms. This was accompanied
      by a reduction in sexual activity and no change in social life or working
      capacity. Data obtained in the group of patients operated showed a significant
      improvement in the perception of the quality of life and psycho-physical well
      being compared to patients receiving medical treatment alone. CONCLUSIONS: From
      this study it can be seen that patients undergoing mitral valve replacement
      surgery experience a marked improvement in the quality of life compared to pre
      operative conditions and to the group of patients receiving medical therapy for
      mitral valve diseases. The use of specific working and social rehabilitation
      programmes can certainly optimise the results also with regard to affective
      relations.

PMID- 8538905
TI  - [Quality of life after an episode of myocardial infarct].
AB  - We studied the quality of life of two groups of myocardial infarction patients
      (AMI) and a control group of normal subjects: 1) 100 post-AMI patients following
      a cardiac rehabilitation programme of 12 weeks (CRG); 2) 33 post-AMI patients
      following a conventional care by cardiologists (CCG); 3) 40 healthy subjects as
      control (CG). To determine the loss of quality of life we administered the
      questionnaire of De Velasco-Del Barrio. The use of the questionnaire was possible
      by authors permission. MI patients had significantly poorer quality of life than
      the healthy subjects (p < 0.0001). Cardiac rehabilitation improved quality of
      life (p < 0.001) more than the conventional care. Women reported poorer quality
      of life that men. Before and after rehabilitation programme the quality of life
      of the subjects age 50 years or more was worse than their younger counterparts.
      Invasive therapies such percutaneous transluminal coronary angioplasty and
      coronary artery bypass grafting are associated with an improvement of post
      operative quality of life. In order to study the influence of social class on
      quality of life we divided our subjects into three groupings: high, medium and
      low according to code representing jobs and professional: a significant
      difference was found between high and low social class (p < 0.03). These findings
      suggest that cardiac rehabilitation may have positive effects on the quality of
      life in the MI patients. Aged patients, women, and with low social position
      reported poorer quality of life that younger, men and high social position
      patients. It seems that these patients should be assessed with psycho-social and
      treated with psychological and social support for improvement their quality of
      life.

PMID- 8538906
TI  - [Role of transesophageal echocardiography in the evaluation of the potential
      embolic risk in left atrial thrombosis. Report of a clinical case].
AB  - We describe the case of a 73-year-old man with cardiac failure due to
      hypertensive heart disease, chronic atrial fibrillation, prior ischemic stroke
      and acute ischemia of the left leg probably embolic in nature, in whom
      transthoracic echocardiography (TTE) detected a large left atrial mass compatible
      with thrombus. Transesophageal echocardiography (TEE) was performed to better
      evaluate the atrial mass. TTE showed a mass that was firmly attached to the wall
      of the left atrium, compact, homogeneous and stationary, indicating a relatively
      low embolic risk. On the other hand TEE clearly detected a marked motility and
      echographic unhomogeneity of the atrial mass, suggesting a poorer prognosis and
      urgent surgical referral due to high impending embolik risk. This case further
      supports the superiority of TEE to TTE in the assessment of intracardiac masses
      and, in particular, of embolik risk in a patient with left atrial thrombosis.

PMID- 8538907
TI  - [Bilateral femoro-popliteal acute recurrent arterial thrombosis in the course of
      heparin-induced thrombocytopenia (white thrombus syndrome)].
AB  - Heparin induced thrombocytopenia with thrombosis, or the "white clot syndrome" is
      a rare but very important complication of heparin therapy. The syndrome is
      idiosyncrasic, immune-mediated and not dose dependent and therefore is equally
      likely to occur with prophylactic and therapeutic heparin dosage regimens. We
      report a typical case of HIT that occurs with prophylactic heparin therapy and
      results in bilateral amputation of the lower limbs. We discuss this important
      condition and some guidelines on its prevention and treatment.

PMID- 8538908
TI  - [Atrial septal aneurysm. Report of two clinical cases and review of the
      literature].
AB  - We report two cases of atrial septal aneurysm, one associated with paroxysmal
      supraventricular tachycardia, the second with atrial septal defect. In both cases
      there were verified some transitory ischemic attacks. Carotid ultrasonography
      excluded atherosclerosis lesions. Two-dimensional transthoracic echocardiography
      showed an atrial septal aneurysm which, in the second case, was associated with
      atrial septal defect as demonstrated by color Doppler. The therapy is discussed
      in the case of septal atrial aneurysm associated with transitory ischemic attack,
      anticoagulant therapy is indicated; in the other, surgical correction of the
      defect is necessary.

PMID- 8538909
TI  - Is microalbuminuria in diabetes due to changes in glomerular heparan sulphate?

PMID- 8538910
TI  - Is type II mixed cryoglobulinaemia an essential part of hepatitis C virus (HCV)
      associated glomerulonephritis?

PMID- 8538911
TI  - The TH1/TH2 concept and its relevance to renal disorders and transplantation
      immunity.

PMID- 8538912
TI  - The diagnosis of renovascular hypertension: state of the art 1995.

PMID- 8538913
TI  - Sodium and insulin--is there a relationship?

PMID- 8538915
TI  - Banff classification for the histological diagnosis of renal graft rejection:
      what are the advantages?

PMID- 8538914
TI  - How do AV fistulae lose function? The roles of haemodynamics, vascular
      remodelling, and intimal hyperplasia.

PMID- 8538916
TI  - Transplantation in primary hyperoxaluria type 1.

PMID- 8538917
TI  - Volaemia and blood pressure in renal failure: have old truths been forgotten?

PMID- 8538918
TI  - Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by
      endothelin in human glomerular epithelial cells.
AB  - The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET)
      peptides was investigated in human glomerular epithelial cells in culture.
      Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and
      dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was
      109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused
      a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry
      studies. The endothelin-1-induced inositol phosphate accumulation was inhibited
      by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a
      selective ETB receptor agonist, showed no effect. The results suggest an ETA
      mediated pathway. This study demonstrates an ETA-mediated transmembrane
      signalling via phospholipase C with consecutive elevation of inositol phosphates
      and intracellular calcium. Since endothelin peptides contribute to both normal
      renal function and renal dysfunction, this study adds further knowledge on
      glomerular cell regulation.

PMID- 8538919
TI  - Angiotensin-II-induced cell hypertrophy: potential role of impaired proteolytic
      activity in cultured LLC-PK1 cells.
AB  - BACKGROUND: Angiotensin II-induced hypertrophy of both mesangial and tubular
      cells has been shown to be caused by enhanced protein synthesis. There are no
      data about its role on protein breakdown. Therefore, protein turnover and
      proteolytic activities were investigated in LLC-PK1 cells. METHODS: Protein
      turnover was measured by determining the incorporation and release of
      [14C]phenylalanine; collagenolytic and gelatinolytic activities were assayed by
      using fluorogenic peptidyl substrates. RESULTS: Angiotensin II (10(-8)-10(-6) M)
      exerted a dose-dependent inhibition of collagenolytic and gelatinolytic
      activities, associated with reduction of protein degradation rate. In addition
      angiotensin II stimulated protein synthesis in the cells. These combined effects
      on protein turnover resulted in an increase in both cell size and cell protein
      content (31.7% after 48 h). However, the rise of cell protein content was only
      partly (48.0%) prevented by the protein synthesis inhibitor cycloheximide (10(
      5)M), which supports the role of decreased protein degradation in the angiotensin
      II-induced cell hypertrophy. The angiotensin-II-induced effects on proteolytic
      activities as well as on cell protein content could be abolished by coincubation
      with the angiotensin II type I-receptor antagonist DuP 753 (10(-6)M). The calcium
      channel blocker verapamil (10(-6)M) ameliorated the impairment of collagenolytic
      activity. On the contrary the calcium ionophore A23187 (10(-6)M) mimicked the
      action of angiotensin II on this enzyme activity (control 34.5 +/- 1.9;
      angiotensin II 24.0 +/- 2.0; A23187 23.0 +/- 2.2 and angiotensin II+verapamil,
      33.8 +/- 2.6 pmol/min/micrograms DNA). The role of cytosolic [Ca2+] in the
      actions of angiotensin II could be finally shown by a dose-dependent rise which
      was partly blunted by verapamil. CONCLUSION: The angiotensin-II-induced
      hypertrophy in LLC-PK1 cells is caused not only by enhanced protein synthesis but
      also by reduced protein degradation. The concomitant decline of collagenolytic
      and gelatinolytic activities may contribute to the accumulation of extracellular
      matrix, and presumably also to cell hypertrophy. These effects are obviously
      mediated via angiotensin II type I receptors and seem to be [Ca2+] dependent.

PMID- 8538920
TI  - Renal tubular function in children and adolescents with Gitelman's syndrome, the
      hypocalciuric variant of Bartter's syndrome.
AB  - Renal tubular function was studied in 14 patients with Gitelman's syndrome and 14
      control subjects. Apart from the biochemical hallmarks of Gitelman's syndrome,
      namely alkalaemia, hyperbicarbonataemia, hypokalaemia, hypomagnesaemia (with
      increased magnesium over creatinine ratio), increased urinary chloride over
      creatinine ratio, and low urinary calcium over creatinine, the patients were
      found to have hyperproteinaemia, hypochloraemia, high total plasma calcium
      concentration, reduced plasma ionized calcium concentration, and high urinary
      sodium excretion. A statistically significant negative linear relationship
      between plasma magnesium concentration and magnesium excretion corrected for
      glomerular filtration was observed in patients. The fractional calcium clearance
      and the urinary excretion of calcium corrected for glomerular filtration was
      significantly decreased in patients. In patients the urinary osmolality after
      overnight water deprivation ranged from 526 to 1067 mmol/kg. Glucosuria and
      aminoaciduria were similar in patients and controls. The results of the study
      demonstrate the renal origin of hypomagnesaemia and hypocalciuria in Gitelman's
      syndrome. The failure to demonstrate hyperaminoaciduria, hyperglucosuria,
      hyperphosphaturia, hyperuricosuria, and severely impaired urinary concentrating
      ability provide evidence for a defect residing in the distal convoluted tubule.

PMID- 8538921
TI  - Urinary and plasma endothelin 1 in essential hypertension and in hypertension
      secondary to renoparenchymal disease.
AB  - An alteration in renal metabolism of endothelin may contribute to hypertension in
      the SHR and it has been shown that the excretion rate of endothelin is reduced in
      patients with essential hypertension. We measured plasma and urinary endothelin 1
      (ET-1) in 20 untreated essential hypertensives with normal renal function, in
      eight normotensive healthy subjects, and in 13 hypertensive patients with primary
      renoparenchymal disease. Plasma ET-1 was higher (P < 0.01) in essential
      hypertensives (median 1.69, interquartile range 1.2-3.3 pg/ml) than in normal
      subjects (0.84, 0.37-1.10 pg/ml) but significantly less (P < 0.01) than in
      hypertensives with renoparenchymal disease (3.57, 1.45-9.52 pg/ml). ET-1 levels
      slightly correlated with diastolic pressure in essential hypertensives (r = 0.43,
      P < 0.05) and tended to be correlated with systolic pressure in hypertensives
      with renal disease (r = 0.47, P = 0.08). ET-1 excretion in essential
      hypertensives (137, 99-154 ng/24 h) and in normal subjects (120, 62-150 ng/24 h)
      was significantly lower than in renal hypertensives (191, 123-241 ng/24 h). The
      ET clearance/GFR ratio (ClET/GFR) was markedly reduced (30%, 21-67%) in essential
      hypertensives and substantially raised in renal hypertensives (164%, 86-314%) in
      comparison with normal subjects (83%, 35-94%). Since the ClET/GFR ratio should be
      100% if all filtered ET-1 is excreted, the data indicate that ET-1 is synthesized
      at a reduced rate and/or broken down at an enhanced rate by the kidney in
      essential hypertension and confirm that there is a high ET-1 generation rate in
      remnant nephrons in hypertension secondary to renal disease.

PMID- 8538922
TI  - Effect of isradipine on renal haemodynamics and systemic blood pressure changes
      induced by intravenous infusion of endothelin in healthy humans.
AB  - BACKGROUND: In some vascular beds calcium-channel-blocking agents have been shown
      to possess some antagonism to endothelin-1 (ET-1)-induced vasoconstriction. This
      issue has not been well investigated in humans, however. METHODS: The study had a
      double-blind cross-over design. In 12 healthy human volunteers we investigated
      the effect of pretreatment with either isradipine 10 mg daily for 1 week or
      placebo on changes in (i) systemic and renal haemodynamics and (ii) renal
      handling of sodium and water induced by intravenous infusion of ET-1 at a rate of
      1 pmol/min/kg for 60 min. RESULTS: Infusion of ET-1 affected systemic
      haemodynamics. The increase in diastolic blood pressure was similar after
      pretreatment with placebo (+6.8%) or isradipine (+5.3%). The changes in renal
      haemodynamics in response to ET-1 infusion were also familiar, e.g. renal plasma
      flow (-32.1% versus -31.2%), glomerular filtration rate (-8.8% versus -10.9%) and
      renal vascular resistance (+55.1% versus +52.7%). Likewise the changes in renal
      handling of sodium and water in response to ET-1 infusion were unaffected by
      pretreatment with placebo or isradipine, e.g. sodium excretion (-44.6% versus 
      40.8%), urine flow rate (-49.8% versus -38.9%) and clearance of lithium (-32.0%
      versus -29.1%). CONCLUSIONS: Intravenous infusion of ET-1 in healthy humans
      discretely increases diastolic blood pressure and profoundly decreases renal
      haemodynamics and excretion of sodium and water. Pretreatment with the calcium
      channel blocking agent isradipine for 1 week in a clinically relevant dose does
      not interfere with the action of ET-1.

PMID- 8538923
TI  - Borderline hypertensive autosomal dominant polycystic kidney disease patients
      have enhanced production of renal dopamine. Normalization of renal haemodynamics
      by DOPA infusion.
AB  - BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) the
      pathophysiology of hypertension, which is frequently observed before loss of
      renal function, is not well understood. We investigated intrarenal dopamine, the
      renin-angiotensin-aldosterone system (RAAS), and plasma endothelin in relation to
      sodium homeostasis as potential hypertensive factors in this disease. METHODS:
      Eight borderline hypertensive ADPKD patients with (near) normal renal function
      and seven matched healthy control subjects were investigated at three levels of
      daily dietary sodium intake: 150, 50 and 450 mmol. In the 450-mmol sodium intake
      period we studied the effects of renally formed dopamine by infusing its
      precursor DOPA (DOPAi.v., 7 micrograms kg-1 min-1). In the 50-mmol sodium intake
      period we studied the influence of the RAAS by administering enalaprilate (42
      micrograms kg-1), followed by angiotensin II (12 ng kg-1 min-1) intravenously.
      GFR and ERPF were measured by continuous infusion of inulin and PAH. RESULTS: At
      all levels of sodium intake sodium balances were equal, but daily urinary
      excretions of dopamine and DOPA were higher (P < 0.01) in the ADPKD patients than
      in the controls. Renal vascular resistance, filtration fraction and blood
      pressure were higher in the ADPKD patients (all P < 0.05) while plasma renin
      activity was similar. DOPAi.v. normalized renal haemodynamics and increased
      plasma endothelin in ADPKD patients (all P < 0.05), while stimulation of
      natriuresis was equal in both groups. Enalaprilate increased plasma endothelin in
      the ADPKD patients and only partially normalized renal haemodynamics.
      CONCLUSIONS: In borderline hypertensive ADPKD patients: (1) urinary dopamine
      excretion is increased at all levels of sodium intake, suggesting that this may
      be needed to maintain sodium balance; (2) stimulation of renal dopamine
      production is able to normalize renal haemodynamics, making dopamine receptor
      agonism a potential therapeutic option; (3) the activity of the RAAS is not
      clearly enhanced; (4) renal vasodilatation increases plasma endothelin levels.

PMID- 8538924
TI  - Expression and function of fibronectin receptors on peripheral mononuclear cells
      in IgA nephropathy.
AB  - The beta 1 integrin family, major adhesive receptors for the extracellular matrix
      (ECM), have been reported to be present in normal and diseased kidneys.
      Attachment of glomerular cells to ECM is mediated by beta 1 integrins. Several
      members of the beta 1 integrins are referred to as VLA (very late activation)
      antigens. Peripheral mononuclear cells also express VLA antigens in both resting
      and activated states. We examined the expression and function of VLA antigens on
      peripheral lymphocytes and monocytes in patients with IgA nephropathy using
      monoclonal antibodies (mAbs) specific for VLA alpha-chains. Peripheral
      lymphocytes from patients with IgA nephropathy expressed VLA-4 alpha and 5 alpha,
      but not VLA-1 alpha, 2 alpha or 3 alpha. Peripheral monocytes from patients with
      IgA nephropathy expressed VLA-2 alpha, 4 alpha and 5 alpha, but not VLA-1 alpha
      or 3 alpha. The expression of VLA adhesive receptors was observed in healthy
      individuals. Adhesion assay to fibronectin revealed augmented adhesion of
      mononuclear cells in IgA nephropathy (P < 0.05), and this increased adhesion was
      inhibited by mAbs to VLA-4 alpha and 5 alpha. The expression of beta 1 integrins
      in IgA nephropathy was similar to that of healthy individuals, but the function
      of these molecules in terms of adhesion to fibronectin though VLA-4 and VLA-5 is
      increased in these patients. These findings suggest that the activation of
      fibronectin receptors on peripheral mononuclear cells plays an important role in
      the pathogenic process of IgA nephropathy.

PMID- 8538925
TI  - T-lymphocyte activation in steroid-sensitive nephrotic syndrome in childhood.
AB  - We undertook a sequential study in 29 children with steroid-sensitive nephrotic
      syndrome (SSNS) off treatment to seek evidence for T-cell activation in relapse.
      T-cell subsets and activation markers were analysed using two-colour flow
      cytometry. Soluble IL2 receptor (sIL2R) was measured in serum and urine by enzyme
      linked immunosorbent assay (ELISA). Fifteen children were examined in remission
      and subsequent relapse (group A) and fourteen remained in remission (group B). In
      group A the proportion of CD4+ cells expressing the activation marker CD25 (alpha
      chain of the IL2 receptor) increased significantly from remission to relapse:
      CD4+25+ cells rose from 5.6 to 7.0% of total lymphocytes, and from 15.8 to 19.1%
      of CD4+ lymphocytes (paired t test: P < 0.0005 and < 0.001 respectively). No
      correlations were found between CD4+25+ cells and plasma albumin or cholesterol
      concentrations. SIL2R concentration in serum did not change in relapse, but
      increased significantly in urine from 272 to 592 U/mg creatinine (P < 0.01). No
      significant difference was found in remission between groups A and B. We conclude
      that early relapse in SSNS is associated with activation of CD4+ (T-helper) cells
      which is not secondary due to the nephrotic state itself.

PMID- 8538926
TI  - Progression rate to end-stage renal failure in non-diabetic kidney diseases: a
      multivariate analysis of determinant factors.
AB  - BACKGROUND: The respective contribution of the type of nephropathy, gender, and
      proteinuria, and of the potentially alterable factors blood pressure level and
      daily protein intake on the rate of progression in non-diabetic renal diseases is
      debated. METHODS: We retrospectively analysed the influence of primary renal
      disease, gender, urinary protein excretion, mean arterial pressure (MAP), and
      dietary protein intake on the rate of decline in creatinine clearance (delta Ccr)
      in 159 adult patients with well-defined nondiabetic kidney diseases. All patients
      had been followed from a baseline Crr of 40-50 ml/min/1.73 m2 until endstage
      renal disease and need for dialysis. RESULTS: Mean (+/- SD) delta Ccr
      (ml/min/1.73 m2/year) was 9.9 +/- 6.5 in 51 patients (45 males) with chronic
      glomerulonephritis, 6 +/- 2.5 in 50 patients (26 males) with polycystic kidney
      disease, 5.5 +/- 2.4 in 17 patients (16 males) with hypertensive
      angionephrosclerosis, and 3.9 +/- 2 in 41 patients (21 males) with chronic
      tubulointerstitial nephritis. delta Ccr was higher in males than in females (7.5
      +/- 5.2 versus 4.8 +/- 2.5; P < 0.001). Linear regression analysis of the whole
      population disclosed a strong relationship between delta Ccr and proteinuria (r2
      = 0.23; P < 0.001), and a weak relationship between delta Ccr and protein intake
      (r2 = 0.03; P = 0.02), but no relationship between delta Ccr and MAP (r2 = 0.01;
      P = 0.23). Stepwise multiple regression analysis identified the type of
      nephropathy, gender, and proteinuria as independent predictive factors of
      progression; however, these factors together accounted for only 36% of the
      variation in delta Ccr, suggesting the contribution of other yet unidentified
      factors. CONCLUSIONS: Primary kidney disease and urinary protein excretion
      (reflecting the severity of renal disease in individual cases) appear as the
      major determinants of the rate of progression, with faster progression in males
      in all types of nephropathy, whereas potentially alterable factors such as blood
      pressure and protein intake had only a modest influence in the range of values
      observed in our patients.

PMID- 8538927
TI  - Time course of growth factor expression in mercuric chloride acute renal failure.
AB  - BACKGROUND: Renal EGF expression decreases in varying models of acute renal
      failure (ARF). We found previously that the loss of distal tubular EGF during
      gentamicin ARF is strongest in the cortex, where proximal tubular injury was most
      severe. To gain more insight into the mechanism underlying this apparent
      anatomical association, renal growth factor expression was investigated during
      mercuric chloride ARF, in which proximal tubular injury is most severe in the
      outer stripe of the outer medulla (OSOM). METHODS: Endogenous renal growth factor
      expression was investigated by RNA hybridization and by immunohistochemistry in a
      rat model of mercuric chloride ARF. In addition we determined temporal and
      spatial profiles of tubular injury, cell proliferation, and mononuclear cell
      infiltration during the 3-week observation period. RESULTS: Serum creatinine
      values were maximal 2 days after treatment and were again normalized at day 6.
      Tubular injury was most severe in the PST and maximal at day 2. Cell
      proliferation was also higher in the PST and maximal at day 4. Three weeks after
      treatment, normal renal morphology was restored. Increased numbers of mononuclear
      cells appeared transiently in the renal interstitium from day 1 on. Most of these
      cells were macrophages and T lymphocytes; macrophages surrounded preferentially
      the severely injured PST in the OSOM. In analogy to gentamicin ARF, renal EGF and
      IGF-I gene expression were decreased early in the setting of mercuric chloride
      ARF. The decrease in distal tubular EGF staining was most pronounced in the OSOM,
      i.e. the anatomical area where mercuric-chloride-induced proximal tubular injury
      was most severe. CONCLUSIONS: Renal EGF and IGF-I gene expression decreases
      strongly during mercuric chloride ARF. The spatial association between the
      initial decrease of distal tubular EGF expression and the zone of major proximal
      tubular injury could originate from metabolic alterations secondary to oxygen
      starvation. A possible role of mononuclear cells remains to be determined.

PMID- 8538928
TI  - Identification of auto-transplanted parathyroid tissue by Tc-99m methoxy isobutyl
      isonitrile scintigraphy.
AB  - Parathyroid tissue is sometimes auto-transplanted into the forearm after 'total'
      parathyroidectomy in patients with renal failure. Recurrent hyperparathyroidism
      demands identification of the source of PTH secretion which cannot be assumed to
      be the forearm. To this end, Tc-99m methoxy isobutyl isonitrile (MIBI)
      scintigraphy was used to identify functioning auto-transplanted parathyroid
      tissue in seven patients undergoing renal replacement therapy (five with
      functioning renal transplants and two on haemodialysis). Serum PTH was estimated
      in venous blood taken proximal and distal to the forearm graft and from the
      contralateral arm, and subsequent Tc-99m MIBI scanning was carried out without
      knowledge of the PTH results. Five patients had a significant gradient in PTH
      levels between sites proximal and distal to the graft, and between the proximal
      site and the contralateral arm, suggesting functioning parathyroid tissue in the
      graft. Subsequent Tc-99m MIBI scintigraphy confirmed the activity of the auto
      transplanted parathyroid tissue in these five patients. In the remaining two
      patients without a significant PTH gradient between the sampling sites, Tc-99m
      MIBI scintigraphy did not identify any functioning forearm parathyroid tissue.
      The scan results therefore correlated well with the gradients in PTH levels,
      suggesting that MIBI scintigraphy can be used to identify functioning auto
      transplanted parathyroid tissue. The results also indicate that any patient who
      has undergone auto-transplantation of parathyroid tissue must have blood samples
      taken from veins proximal to the graft and either distal to it, or from the
      contralateral arm when parathyroid status is re-assessed, particularly when
      surgery is being considered for recurrent hyperparathyroidism.

PMID- 8538929
TI  - Effect of gastric acid secretion on intestinal phosphate and calcium absorption
      in normal subjects.
AB  - BACKGROUND: Phosphate-induced hyperparathyroidism still represents an intriguing
      problem in dialysis patients. Postprandial hyperphosphataemia is considered to be
      the main stimulus to parathyroid hyperfunction, and therefore many efforts have
      focused on the use of phosphate binders to prevent phosphate absorption. METHODS:
      We investigated whether the pH-mediated gastric ionization of calcium phosphate
      dietary salts is necessary for its intestinal absorption. In eight normal
      subjects we measured 24-h urinary calcium phosphate excretion and the
      postprandial blood calcium phosphate profile after a meal containing 1 g of
      calcium and 2 g of phosphate salts in a crossover placebo-omeprazole study. On
      two occasions the subjects received either placebo or omeprazole 60 mg/day 2 days
      before and during the day test. RESULTS: Serum gastrin levels were measured as an
      indicator of achlorhydria and were 13.7 +/- 1 pg/ml after placebo and 30.4 +/-
      4.7 after omeprazole (P < 0.003). Postprandial plasma phosphate profiles were not
      significantly different between the two studies (+36 +/- 8% after placebo and +24
      +/- 8% after omeprazole, NS), while plasma calcium increased by +6.1 +/- 1% after
      placebo and decreased by -4.2 +/- 0.7% after omeprazole (P < 0.01). The 24-h
      urinary phosphate excretion was 1068 +/- 85 mg after placebo and 773 +/- 55 after
      omeprazole (P < 0.002), while the 24-h urinary calcium excretion was 360 +/- 21
      after placebo and 238 +/- 15 after omeprazole (P < 0.0001). A negative
      relationship was observed between absolute changes in plasma gastrin and those in
      urinary calcium (P < 0.009) and phosphate (P < 0.05). CONCLUSIONS: The inhibition
      of gastric acid secretion by omeprazole significantly reduces both urinary
      phosphate and calcium excretion after an oral load. The behaviour of the
      postprandial calcium-phosphate plasma profile suggests that gastric acid
      inhibition is more effective in reducing calcium rather than phosphate dietary
      salts absorption in normal subjects.

PMID- 8538930
TI  - Detection of primary hyperoxaluria type 2 (L-glyceric aciduria) in patients with
      maintained renal function or end-stage renal failure.
AB  - Primary hyperoxaluria (PH) type 1 and type 2 are autosomal recessive defects of
      oxalate metabolism resulting from glyoxylate accumulation which occurs by two
      distinct pathways. PH1 is associated to glycolic aciduria; PH2 to L-glyceric
      aciduria. Because hyperoxaluria leads to nephrolithiasis or nephrocalcinosis in
      both, they can be differentiated only through detection of the associated
      acidurias. However, glycolate and L-glycerate assays are not widely available
      and, in the setting of ESRF, diagnosis is hampered by a number of misleading
      events. At any stage of the disease diagnosis is crucial because there are
      differences between the two forms in clinical behaviour, long-term prognosis, and
      treatment. In this paper we outline diagnostic criteria for identification of PH2
      in two patients, one with maintained renal function and one with ESRF on CPD,
      based on the use of a novel HPLC assay of L-glycerate in different body fluids.
      With the routine application of this procedure PH2 has been identified in two of
      23 patients fulfilling criteria for diagnosis of PH. This suggests that the type
      2 variant of PH may occur more frequently than so far suspected, and should be
      tested for even in the setting of ESRF.

PMID- 8538931
TI  - Regulation of nitric oxide synthesis in uraemia.
AB  - Nitric oxide (NO) is a cell-to-cell mediator involved in the regulation of
      vascular tone and in the mechanisms of host defence. Since uraemic syndrome is
      characterized by abnormalities in blood pressure and flow and by impairment of
      white cell function, we studied the regulation of nitric oxide synthase (NOS)
      activity by uraemic plasma. We used three different cellular types having
      different levels of NOS activity: tEnd.1 murine endothelial cell line transformed
      by mT oncogene of polyomavirus had a high NOS activity and expressed endothelial
      NOS (eNOS) and inducible-NOS (iNOS) isoforms; human endothelial cells from cord
      umbilical vein (HUVEC) had low enzymatic activity and expressed only eNOS;
      finally, J774 murine macrophage line was characterised by iNOS induced after
      treatment with cytokines. We demonstrated that most (79%) of end-stage uraemic
      plasma studied inhibited NOS activity in tEnd.1 and in cytokine induced -J774,
      whereas they were ineffective on HUVEC. Twenty percent of plasma samples (14 of
      67) activated NOS activity in tEnd.1 and in J774 cells, but not in HUVEC,
      suggesting the presence of molecule(s) which influence iNOS. The effect of plasma
      was not dependent on the type of haemodialysis treatment. A great number of
      plasmas from patients with moderate renal failure also inhibited NOS activity in
      tEnd.1, suggesting that the accumulation of molecules affecting NOS was caused by
      the renal failure rather than the haemodialytic treatment. However, the
      haemodialysis modified the effect of plasmas on NOS activity. Plasma taken after
      haemodialysis session showed a reduced inhibitory activity in tEnd.1 and in some
      cases it enhanced NOS activity. Simultaneously, molecules reducing NOS activity
      accumulated in the ultrafiltrate. The plasma concentration of NG-NG dimethyl-L
      arginine (asymmetrical dimethylarginine, ADMA), an inhibitor of NOS, increased in
      end-stage uraemic patients and was reduced by haemodialysis. However, the
      concentrations reached in uraemic plasmas were lower than the ADMA IC50 on tEnd.1
      NOS, indicating that this compound contributes with other molecules to the
      inhibitory effect of uraemic plasma. Haemodialysis reduced also the enhanced
      effect exerted by some plasmas on NOS in J774. Therefore, the effect of end-stage
      uraemic plasma on NOS activity derive from the balance between inhibitors and
      activators.

PMID- 8538933
TI  - Creatinine kinetic modelling: a simple and reliable tool for the assessment of
      protein nutritional status in haemodialysis patients.
AB  - While the mathematical modelling of urea kinetics is in wide use for evaluating
      treatment adequacy and protein nutrition in dialysis patients, the kinetics of
      creatinine generation in dialysis patients has been relatively unexplored. In
      this study creatinine kinetic modelling as a clinical tool was investigated in a
      group of 90 patients treated by haemodialysis (n = 20), haemodiafiltration (60),
      haemofiltration (7), or biofiltration (3) over a 6-36-month period. A single pool
      model of creatinine kinetics was employed to obtain monthly values of creatinine
      distribution space and creatinine appearance rate. Extrarenal creatinine
      degradation rate, estimated using a clearance of 0.038 l/kg/24 h as suggested by
      Mitch and co-workers, was added to creatinine appearance rate in urine and
      dialysate to calculate a corrected creatinine index (CI). Extrarenal degradation
      accounted for 12 +/- 2% of CI. CI was higher in males (22.4 +/- 4.5 mg/kg/24 h)
      than females (19.8 +/- 4.8) and decreased with age, falling off more sharply for
      the female group (CI = 29.9-0.185.age, R = 0.72) than the males (CI = 24.1
      0.030.age, R = 0.31). CI was found to correlate strongly with protein catabolic
      rate determined by urea kinetic modelling (CI = 8.84 +/- 10.91.PCR). Low or
      reduced CI was associated in this study group with severe malnutrition status and
      high mortality rate. CI is suggested as a strong predictor of patient morbidity
      and mortality.

PMID- 8538932
TI  - Haemodynamic changes and exercise tolerance in dialysis patients treated with
      erythropoietin.
AB  - The aim of our study was to evaluate cardiovascular function at rest and during
      exercise in dialysis patients before and after treatment with Epo and to examine
      the changes in left ventricular mass as the consequence of treatment for anaemia.
      We applied echocardiography and radionuclide ventriculography at rest and after
      exercise in our research. Following treatment with Epo there was a decrease in
      the initially high cardiac output (CO) and cardiac index (CI) from 7.5 to
      6.31/min and from 4.3 to 3.61/min/m2 respectively. No changes were noted in mean
      diastolic (DPB) and mean blood pressure (MBP), as well as the initially increased
      peripheral resistance index (TPRi) of 2582.3 +/- 2097.3 dyn-s-cm-5.m2.
      Nevertheless, end-diastolic (EDV) and end-systolic (ESV) volume were
      significantly decreased (P < 0.05), but the ejection fraction (EF) remained
      unchanged (73.9%). The decrease in the mean values for left ventricular mass
      (LVM) was significant only within the subgroup of dialysed patients who initially
      had larger left ventricular mass (P < 0.01). The functional capacity of the CV
      system measured during exercise increased from four metabolic equivalents (METs)
      to 6 METs (P < 0.01). A significant increase in blood volume was also observed
      following treatment of anaemia. The haemodynamic consequences of Epo therapy for
      the treatment of anaemia were quite positive. However, we would like to point out
      certain concerns regarding the dialysed patients with initially lower values for
      left ventricular mass and cardiac output, since the patients within this group
      developed left ventricular hypertrophy and an increase in cardiac output.

PMID- 8538934
TI  - Intradialytic parenteral nutrition in malnourished patients on chronic
      haemodialysis therapy.
AB  - BACKGROUND: Malnutrition is frequently encountered in patients on regular
      haemodialysis therapy and presents an important determinant of morbidity and
      mortality. Usual therapeutic approaches to alleviate malnutrition have been
      unsuccessful. The objective of this study was to assess the impact of
      intradialytic parenteral nutrition (IDPN) with amino acids (in combination with a
      glucose-containing dialysate) on nutritional parameters and immunocompetence in
      patients on regular haemodialysis treatment. METHODS: Effects of IDPN were
      evaluated in 16 malnourished patients. After a run-in period of 4 weeks (to
      define stable baseline conditions) 0.8 g amino acids/kg bodyweight using a novel
      amino-acid solution (adapted to metabolic alteration of uraemia and including the
      dipeptide glycyl-tyrosine as tyrosine source) was infused thrice weekly during
      each haemodialysis session for 16 weeks. RESULTS: Intradialytic amino-acid
      infusion was well tolerated and the dipeptide was rapidly utilized with only
      traces being detectable in plasma after dialysis. Visceral protein synthesis was
      improved, serum albumin, prealbumin, and cholinesterase increased during IDPN (P
      < 0.05). As indicators of augmented immunocompetence skin test reactivity against
      multiple antigens was improved (P < 0.02) and total lymphocyte count was raised
      (P < 0.05). Plasma amino acid pattern did not deteriorate but failed to normalize
      during IDPN and phenylalanine/tyrosine ratio remained stable. Anthropometric
      measurements and eating behaviour as assessed by dietary records were not altered
      during IDPN. CONCLUSIONS: Even using a simple and limited intradialytic
      nutritional support with amino acids can improve visceral protein status and
      stimulate immunocompetence in malnourished patients on regular haemodialysis
      therapy.

PMID- 8538935
TI  - 'Paradoxical' rise in blood pressure during ultrafiltration in dialysis patients.
AB  - In some hypertensive haemodialysis (HD) patients, blood pressure rises further
      during ultrafiltration (UF). We investigated seven such patients, who were not
      responsive to hypotensive drugs, including converting enzyme inhibitors. All had
      marked cardiac dilatation, but most were non-oedematous. They were treated with
      repeated intense UF while monitoring cardiac function by echocardiography. After
      a variable time period they all became (near) normotensive without medication.
      Mean systolic and diastolic blood pressure decreased by 46 +/- 18 and 22 +/- 9
      mmHg respectively while bodyweight decreased by a mean of 6.7 +/- 3.0 kg. Plasma
      volume decreased by 22%, and mean albumin increased from 3.9 +/- 0.3 to 4.2 +/-
      0.3 g/dl. Cardiothoracic index decreased from a 0.56 +/- 0.02 to 0.45 +/- 0.03.
      Mitral and tricuspid insufficiency was present in four patients and improved or
      disappeared in all of them. Diameters of the inferior vena cava, left atrium, and
      end systolic and diastolic left ventricle markedly decreased in all patients.
      Ejection fraction increased, but remained subnormal in some patients, while
      cardiac output increased in five and decreased in two patients. We conclude that
      paradoxical blood pressure rise with UF usually occurs in the presence
      overhydration and cardiac dilatation and should be treated by intensified UF. The
      explanation of this phenomenon remains speculative.

PMID- 8538936
TI  - Failure of arginine-vasopressin and other pressor hormones to increase in severe
      recurrent dialysis hypotension.
AB  - BACKGROUND: Recurrent dialysis hypotension is common in long-term dialysis
      patients. Arginine-vasopressin (AVP) is a potent vasoconstrictor hormone, release
      of which is stimulated in hypotension. STUDY DESIGN: We measured AVP as well as
      adrenaline and noradrenaline in 23 patients with recurrent dialysis hypotension
      during severe symptomatic episodes of dialysis hypotension (BP syst. < 70 mmHg).
      We also tested autonomic function (amyl nitrate inhalation, cold pressor test)
      during the interdialytic interval. RESULTS: We observed that systolic blood
      pressure decreased from 127 +/- 8 (at the end of the first hour of dialysis;
      taken as control state) to 64 +/- 1 mmHg (symptomatic hypotension) in 23
      patients. In six of the 23 patients hypotension was accompanied by nausea, which
      is a known direct stimulus of AVP. In these six patients, plasma AVP showed a
      large increase: control state, 6.2 +/- 0.9; hypotension, 130.4 +/- 51.1 pg/ml; P
      < 0.5). Of the remaining 17 patients without nausea, AVP fell moderately in nine
      and increased in eight. Taken together, this group of 17 hypotensive patients
      failed to show significant AVP stimulation: control state, 9.0 +/- 1.4;
      hypotension, 13.8 +/- 3.8 pg/ml, NS). Adrenaline and noradrenaline did not change
      during hypotension. During autonomic testing the patients with recurrent dialysis
      hypotension (compared to healthy controls) showed blunted baroreflex response
      (assessed by amyl nitrate inhalation) but intact sympathetic outflow (assessed by
      cold pressor test). CONCLUSION: The observations of AVP are taken as further
      evidence of defects in the afferent rather than the efferent limb of autonomic
      reflexes in dialysis patients with recurrent dialysis hypotension.

PMID- 8538937
TI  - The renal medulla in acute renal allograft rejection: comparison with renal
      cortex.
AB  - A retrospective cohort study was undertaken to evaluate the diagnostic value of
      the renal medulla in acute renal allograft rejection (ARAR). One hundred and
      ninety-five biopsies from 98 patients were randomly selected out of 565
      transplant biopsies. Biopsies were graded blindly from Grade 0 (no rejection) to
      Grade 3 (severe rejection) using standard criteria; ARAR was confirmed by a fall
      in all cases of mean serum creatinine concentration from 0.331 +/- 0.182 to 0.184
      +/- 0.079 mmol/l, with anti-rejection therapy. In the 43 biopsies which contained
      both cortex and medulla, the ARAR grades and the intensities of mononuclear cell,
      plasma cell, polymorphonuclear cell and eosinophil infiltrates, and of
      interstitial oedema and haemorrhage, were similar in cortex and medulla
      (Spearman's Rank Correlation r = 0.55-0.81, P < 0.001). The sensitivity,
      specificity and overall accuracy of medullary changes in predicting ARAR changes
      in the cortex were 77%, 100% and 38%, respectively. Acute vascular rejection
      changes could not be compared between renal cortex and renal medulla because of
      the anatomical differences between cortex and medulla. Further evaluation of ARAR
      in the all 195 biopsies, of which 188 had cortical tissue and 50 had medullary
      tissue, showed no significant differences in histological features (P > 0.05),
      except for more cortical biopsies with plasma cells (29%) than medullary biopsies
      with plasma cells (10%; P < 0.02). It is concluded that: (1) ARAR histological
      changes are similar in cortex and medulla; (2) the predictive value of ARAR
      medullary changes for cortical rejection changes has low sensitivity (77%) and
      high specificity (100%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8538938
TI  - Clinical evaluation of an optimized 1.1% amino-acid solution for peritoneal
      dialysis.
AB  - A significant percentage of dialysed patients have inadequate protein intake. One
      strategy for treating the protein malnutrition in peritoneal dialysis patients is
      to replace glucose in the dialysis solution by amino acids. A new peritoneal
      dialysis solution containing 1.1% amino acids in a formulation optimized for
      renal patients and with a lactate concentration of 40 mmol/l has been evaluated.
      Fifteen CAPD patients completed a non-randomized prospective 3-month study. Each
      patient received 2 litres of the optimised 1.1% amino acid solution for the
      second exchange of the day with a dwell time of 5-6 h. Indicators of efficacy
      were serum albumin and transferrin. After 3 months of intraperitoneal amino
      acids, serum albumin levels significantly increased from 32.7 +/- 2.3 to 35.1 +/-
      2.2 g/l (mean +/- SD; P < 0.01). This occurred in parallel with a significant
      increase in transferrin levels from 2.21 +/- 0.26 to 2.39 +/- 0.27 g/l (P <
      0.05). As expected, urea rose from 23.7 +/- 6.8 to 29.9 +/- 9.4 mmol/l.
      Interestingly bicarbonate did not change (25.5 +/- 4.2 versus 25.2 +/- 3.3
      mmol/l). These results suggest that the optimized formulation is effective in
      improving nutritional parameters in CAPD patients while avoiding unwanted side
      effects such as acidosis.

PMID- 8538939
TI  - Extramedullary haematopoeisis in the renal parenchyma as a cause of acute renal
      failure in myelofibrosis.

PMID- 8538940
TI  - Acute renal failure associated with alpha-interferon therapy for chronic
      hepatitis B.

PMID- 8538941
TI  - Pulmonary acremonium abscesses and gastrointestinal tuberculosis manifested as
      massive upper gastrointestinal bleeding.

PMID- 8538942
TI  - ANCA-positive crescentic glomerulonephritis in chronic bronchiectasis.

PMID- 8538943
TI  - Primary ascites as the presenting feature of systemic lupus erythematosus:
      response to cyclosporin therapy.

PMID- 8538944
TI  - Henoch-Schonlein purpura and alpha 1-antitrypsin deficiency.

PMID- 8538945
TI  - Spontaneous disappearance of complicated staghorn calculus.

PMID- 8538946
TI  - Reversal of the nephrotic syndrome due to renovascular hypertension by successful
      percutaneous angioplasty and stenting.

PMID- 8538947
TI  - Severe aplastic anaemia due to B19 parvovirus infection in renal transplant
      recipient.

PMID- 8538948
TI  - Traumatic infarct at the lower pole of a renal transplant secondary to seat belt
      compression.

PMID- 8538949
TI  - Seven-year survival of renal transplant for oxalate nephropathy due to short
      bowel syndrome.

PMID- 8538950
TI  - The child with renal insufficiency and a 'white kidney' by ultrasound.

PMID- 8538951
TI  - Effect of pefloxacin on experimental adriamycin-induced nephrotic syndrome.

PMID- 8538952
TI  - Behcet's syndrome presenting as end-stage chronic renal failure due to
      amyloidosis.

PMID- 8538953
TI  - Amyloid deposition in the thyroid gland in patients with amyloidosis: an
      incidence study with fine-needle aspiration biopsy of the thyroid.

PMID- 8538955
TI  - Treatment options for HCV-positive haemodialysis patients?

PMID- 8538954
TI  - Prevention of hepatitis C infection in haemodialysis units.

PMID- 8538956
TI  - Complement activation by LDL-apheresis using dextran sulphate.

PMID- 8538957
TI  - ACE inhibitors do not decrease rHuEpo response in patients with end-stage renal
      failure.

PMID- 8538958
TI  - Tolerance and pharmacokinetics of antimony in a patient with renal failure.

PMID- 8538959
TI  - Typhoid vaccination and IgA nephropathy.

PMID- 8538960
TI  - Nutritional antioxidants: their role in disease prevention.

PMID- 8538961
TI  - Trends in coronary heart disease risk factors in Auckland 1982-94.
AB  - AIMS: This paper describes trends in major coronary heart disease risk factors
      over the period 1982 to 1994 in the city of Auckland, New Zealand. METHODS:
      Coronary heart disease risk factor levels were measured in three cross-sectional
      surveys in Auckland in 1982, 1986-8 and 1993-4, following a standardised
      protocol. Random samples of nonMaori, nonPacific Island adults aged 35-64 years
      were selected from the Auckland general electoral rolls using similar methods in
      all three surveys. Participants attended a study centre for interview and risk
      factor measurement. RESULTS: The analyses presented are based on samples of 1029
      men and 569 women in 1982, 541 men and 365 women in 1986-8, and 712 men and 685
      women in 1993-4. The data are directly age-standardised to the 1986 New Zealand
      population. Over the 12 year period the prevalence of self-reported cigarette
      consumption declined significantly from 28.6% to 16.9% in men and from 24.5% to
      14.8% in women. Mean serum total cholesterol showed little change between 1982
      and 1986-8 but declined significantly between 1986-8 and 1993-4 by approximately
      6% from 6.12 mmol/L to 5.73 mmol/L in men and by 9% from 6.17 mmol/L to 5.60
      mmol/L in women. Mean serum high density lipoprotein (HDL) cholesterol showed a
      modest increase between 1982 and 1986-8 but declined significantly between 1986-8
      and 1993-4 by 12% from 1.25 mmol/L to 1.10 mmol/L in men and by 9% from 1.55
      mmol/L in women to 1.40 mmol/L in women. The total cholesterol to HDL cholesterol
      ratio increased significantly between 1986-8 and 1993-4 by 6% in men but showed
      little change in women. Mean blood pressure levels fell by 4-6 mmHg systolic and
      6-7 mmHg diastolic over the 12 year period in men and women. Mean body mass index
      increased significantly from 25.6 to 26.4 in men and from 24.5 to 25.1 in women
      during this period. CONCLUSIONS: Over the 12 year period, 1982-94 there have been
      substantial reductions in the prevalence of self reported cigarette smoking, mean
      serum total cholesterol levels and mean blood pressure levels in middle aged
      Aucklanders. Of concern, the prevalence of obesity has increased and mean serum
      HDL cholesterol levels have fallen over the period. Coronary heart disease
      prevention and control programmes appear to have been successful in reducing the
      prevalence of most major coronary heart disease risk factors however some
      reorientation will be required to redress the adverse trends in HDL cholesterol
      levels and obesity.

PMID- 8538962
TI  - A national survey of cigarette smoking in fourth-form school children in New
      Zealand.
AB  - AIMS: To determine the prevalence of cigarette smoking in 14 and 15 year old
      school children in New Zealand and to examine associated risk factors. METHODS:
      Nationwide cross-sectional survey of fourth-form school children in New Zealand
      by means of an anonymous self administered questionnaire in November 1992.
      RESULTS: Questionnaires from 14,097 fourteen and fifteen year-olds were analysed.
      65.6% had tried smoking, and 36.1% regarded themselves as smokers. Females and
      Maori had significantly higher prevalence rates. Of Maori females 44.6% were
      current smokers (more than one per month) compared to 24.0% for the whole group,
      and 33.0% were daily smokers. Pacific Island students, who have similar
      socioeconomic disadvantage to Maori, have a lower relative risk of smoking (RR)
      0.79, (95% confidence interval (CI) 0.68, 0.91), than Europeans. Major
      independent risk factors were identified and population attributable risk was
      calculated for parental smoking (22.9%), poor knowledge of adverse health effects
      (7.3%) and watching televised sports (13.4%). These three modifiable factors
      accounted for 36.1% of the total smoking prevalence in these children.
      CONCLUSION: The continued high prevalence of smoking in New Zealand children,
      especially in Maori and in females, prove current public health measures to be
      inadequate. Our results suggest that strategies aimed at decreasing parental
      smoking, improving student knowledge of adverse health effects and preventing
      tobacco sponsorship of television sports could greatly decrease the smoking
      prevalence in this age group.

PMID- 8538963
TI  - Osteosarcoma in New Zealand 1981-7: an overview.
AB  - AIMS: To examine the incidence, and results of treatment of osteosarcoma in New
      Zealand between 1981 and 1987. METHOD: Data was obtained from the Cancer Registry
      for all patients registered with osteosarcoma between 1981 and 1987. RESULTS:
      There were 104 patients in the study group. There was a peak incidence in the
      second decade with a second smaller peak in the seventh and eight decades. The
      overall 5 year survival rate was 29%. For the group aged under 30 years there was
      a 44% 5 year survival rate. Those aged over 60 years had a 3.2% 5 year survival.
      Survival rates were better when treated with surgery and chemotherapy and where
      the tumour was of the appendicular skeleton. CONCLUSION: This is a mixed group of
      patients. The 5 year survival rates appear to be at the lower end of the spectrum
      of the results reported for similar groups in other countries.

PMID- 8538965
TI  - Rest home policy about cardiopulmonary resuscitation and life threatening illness
      in their residents.

PMID- 8538964
TI  - Is New Zealand's recent increase in campylobacteriosis due to changes in
      laboratory procedures? A survey of 69 medical laboratories.
AB  - AIMS: To evaluate the contribution of changing procedures in microbiology
      laboratories over the previous 5 years to the increase in campylobacteriosis
      notifications. To assess whether regional differences in notification rates are
      due to variations in laboratory procedures. METHODS: A questionnaire was sent to
      69 New Zealand medical laboratories, requesting data on their identification
      procedures for enteric pathogens, including campylobacter. RESULTS: Changes over
      the last 5 years in laboratory techniques were insufficient to account for a
      marked increase in campylobacter isolations. On the basis of data provided by 12
      laboratories, the number of specimens that grew campylobacter increased by 49%
      between 1992 and 1993. Differences in laboratory methods do not explain regional
      differences in campylobacter notification rates. CONCLUSION: Changes in
      laboratory methodologies over the last 5 years do not appear to account for the
      recent national increase in campylobacteriosis notifications.

PMID- 8538966
TI  - Acute polymyositis and myoglobinuric renal failure associated with influenza A
      infection.

PMID- 8538967
TI  - Screening for diabetes in asymptomatic individuals. New Zealand Society for the
      Study of Diabetes.

PMID- 8538968
TI  - Continuing problems with the use of Augmentin for urinary tract infections.

PMID- 8538969
TI  - Microcytic anaemia and depression in hyperthyroidism.

PMID- 8538970
TI  - Seat belts and pregnancy.

PMID- 8538971
TI  - Warfarin therapy at 6 pm.

PMID- 8538972
TI  - Toxicity of herbal products.

PMID- 8538973
TI  - Hospital admissions and deaths due to congestive heart failure in New Zealand,
      1988-91.
AB  - AIMS: Congestive heart failure is believed to be a major public health problem in
      most Western countries; however, little is known about the extent of morbidity
      and mortality from congestive heart failure in New Zealand. This paper reports
      data on hospital admissions and mortality due to congestive heart failure in New
      Zealand during the years 1988-91. METHODS: All data were obtained from the New
      Zealand Health Information Service. Deaths from congestive heart failure were
      identified from ICD-9 codes indicating a primary diagnosis of congestive heart
      failure. Hospitalisations for congestive heart failure were identified both from
      ICD-9 codes indicating a primary diagnosis of congestive heart failure and from
      codes indicating a diagnosis of congestive heart failure secondary to chronic
      rheumatic heart disease, ischaemic heart disease or valvular heart disease
      (nonrheumatic). RESULTS: Each year there was an average of about 850 deaths
      ascribed to heart failure; two-thirds of these occurred in patients over the age
      of 75 years. Each year there was also an average of about 8000 hospital
      admissions of about 5000 patients for congestive heart failure; 75% of these
      admissions involved patients over 65 years old. The mean duration of hospital
      stay for congestive heart failure was 16 days. On this basis, it is estimated
      that hospital admissions for congestive heart failure are likely to cost about
      NZ$50 million each year, or about 1% of the total health budget. CONCLUSIONS:
      Congestive heart failure is clearly a major public health problem in New Zealand
      with high hospitalisation and mortality rates. Several strategies have been
      proven to reduce mortality and hospital admissions for congestive heart failure
      and these should be utilised widely in patients at risk.

PMID- 8538974
TI  - Telephone support for pregnant women: outcome in late pregnancy.
AB  - AIM: The aim of the study was to test the psychosocial benefits of a telephone
      support program for pregnant women. METHOD: Randomised controlled trial. The
      study sample were women recruited from an antenatal clinic and general practice
      surgeries who were less than 20 weeks gestation and either single or in a
      relationship where the partner was unemployed. Women in the intervention group
      received weekly telephone calls throughout their pregnancy. All women were
      interviewed initially and at 34 weeks gestation. There were 66 women in the
      control group and 65 women in the intervention group. RESULTS: The intervention
      and control groups did not differ significantly on the psychosocial measures at
      baseline. Comparisons at 34 weeks were made by analysis of covariance using the
      baseline scores. The intervention group at 34 weeks had lower stress scores than
      the control group (means 16.5 vs 18.4, p = 0.02), lower trait anxiety (means 35.2
      vs 39.4, p = 0.04) and less depressed mood (means 6.6 vs 8.1, p = 0.02). Self
      esteem was higher for the intervention group (means 34.9 vs 32.5, p = 0.008). The
      intervention failed to alter smoking but the intervention women did report more
      use of community resources (p = 0.02) and were less likely to skip meals (p =
      0.03). CONCLUSION: A low cost health promotion program of telephone support
      during pregnancy can significantly improve a woman's psychosocial status during
      pregnancy.

PMID- 8538975
TI  - The length of the referral chain after failing preschool tympanometry.
AB  - AIMS: To describe the time intervals during the process of detection and
      management of chronic secretory otitis media/glue ear. METHOD: Tympanometry
      records of 508 preschool children who failed both tympanometry screening and the
      subsequent retest were examined. Additional information was obtained from 205
      parents/caregivers by telephone interview. RESULTS: Calculations of time
      intervals between tympanometry screening and retesting showed that 75% of
      children had been retested within 20 weeks and 95% by 40 weeks. Two-thirds (67%)
      of children had visited their general practitioner within 4 weeks of failing
      their retest, although 13% had still yet to be seen by 20 weeks. The mean time
      interval between the initial general practitioner visit and subsequently being
      seen by an ENT specialist was 20 weeks in the public system compared to 5 weeks
      if seen privately (p < 0.001). CONCLUSION: The preschool tympanometry screening
      programme functioned well, although there were delays in retesting 25% of
      preschoolers. There were substantial time intervals for some children for each
      link in the referral chain. The reasons for these delays needs investigation to
      determine how much it is a part of the treatment process and how much due to
      waiting list problems.

PMID- 8538976
TI  - Medical discipline and sexual activity between doctors and patients.
AB  - AIM: The Medical Council of New Zealand has adopted a policy which presumes that
      any sexual contact between a doctor and patient is unacceptable. This 'zero
      tolerance' approach will presumably form the basis of disciplinary investigations
      and charges. METHODS: All 412 Auckland general practitioners on the indicative
      register were surveyed by mail, and asked to indicate into which disciplinary
      category each of six scenarios fell. RESULTS: One hundred and sixty-five (40%)
      completed forms were received. Sixty-two percent of respondents did not believe a
      disciplinary offence was committed when a sexual relationship developed after a
      general practitioner invited a patient to meet her at a bar for a drink, as long
      as the patient was then advised to seek the services of another general
      practitioner. CONCLUSION: Under New Zealand law a disciplinary tribunal merely
      transmits the standards of an accused doctor's colleagues. It is argued that a
      simple qualitative survey demonstrating that colleagues do not regard an action
      as meriting disciplinary action may provide a complete defence to any charge.

PMID- 8538977
TI  - Naproxen induced thrombocytopenia: a case report.

PMID- 8538978
TI  - The management of acute viral croup. The Respiratory Committee of the Paediatric
      Society of New Zealand.

PMID- 8538979
TI  - Centre for Adverse Reactions Monitoring report for the year ending 30 June, 1994.

PMID- 8538980
TI  - Cot death and cot mattresses.

PMID- 8538981
TI  - Opioids in chronic pain of non-malignant origin: an interim consensus.

PMID- 8538982
TI  - EGb 761 and the recovery of ion imbalance in ischemic reperfused diabetic rat
      retina.
AB  - We studied the effects of a free-radical scavenger, EGb 761, on electrolyte
      shifts (Na+, Ca2+, and K+) induced by ischemia and reperfusion in the retinas
      obtained from streptozotocin-induced diabetic rats. Eyes were subjected to 90 min
      ischemia followed by 24 h of reperfusion by clamping and releasing the central
      retinal artery. Ten days before the induction of ischemia and reperfusion,
      diabetic rats received a daily dose of 25, 50, and 100 mg/kg p.o. of EGb 761,
      respectively (n = 12 in each group). In the drug-free diabetic control group, 90
      min ischemia followed by 24 h of reperfusion resulted in an increase in retinal
      Na+ and Ca2+ (measured by atomic absorption spectrophotometry) compared to
      nonischemic control values of 73 +/- 4 and 2.6 +/- 0.3 mumol/g dry weight to 113
      +/- 5 (p < 0.05) and 5.3 +/- 0.3 mumol/g dry weight (p < 0.05), respectively.
      Tissue K+ content was significantly reduced compared to its nonischemic diabetic
      control value of 268 +/- 7 to 213 +/- 6 mumol/g dry weight (p < 0.05). EGb 761
      dose-dependently reduced reperfusion-induced ion imbalance, improving the
      recovery of ion content in diabetic rat retina. EGb 761 did not reduce blood
      glucose in streptozotocin-induced diabetic rats. Therefore we may conclude that
      these protective effects of EGb 761 are independent of blood glucose content or
      of the severity of diabetes and protect against electrolyte shifts directly in
      retinal cells.

PMID- 8538983
TI  - Delay of pattern electroretinogram peaks and its correlation to contrast
      threshold for motion perception in glaucoma.
AB  - Peak latencies of pattern electroretinogram (PERG) were compared between
      glaucomatous eyes and non-glaucomatous eyes. Contrast threshold for motion
      perception (CTMP) was also measured with a new device in addition to routine
      static contrast sensitivity, static visual field and visual acuity. In the
      present recording, configurations for PERG, i.e. low reversal rate, low mean
      luminance and presence of background illumination, the PERG peak and trough (P1
      and N2, respectively) latencies, were significantly prolonged in the glaucomatous
      eyes. Although both of the two PERG latencies were strongly correlated with the
      CTMP, only the P1 peak latency was strongly correlated with the perimetric
      indices. These results suggest that the P1 and N2 latencies reflect different
      aspects of signal processing in the retina, especially for moving targets.

PMID- 8538984
TI  - Histological and immunohistochemical study of idiopathic epiretinal membrane.
AB  - We used electron microscopy and light-microscopic immunohistochemistry of
      cellular and extracellular markers to characterize the cellular and extracellular
      components of 15 surgically resected idiopathic epiretinal membranes (IEMs). Ten
      specimens from the eyes with posterior vitreous detachment (PVD) consisted of
      inner limiting membrane, collagen layer and a flattened cell layer. Six out of
      the 10 specimens were also examined immunohistochemically, and fibronectin and
      type I, II, III and IV collagens were identified in a characteristic lamellar
      construct in the IEMs. On the other hand, 5 specimens obtained from the eyes
      without PVD consisted mainly of a thick layer of collagen fibrils with or without
      a flattened cell layer. Two of the 5 specimens were also examined
      immunohistochemically, and the collagen fibrils in the specimens were identified
      as type II collagen. Glial cells (glial fibrillary acidic protein-immunoreactive
      cells) were also identified in 3 specimens. These results indicate that there are
      some variations in the IEMs.

PMID- 8538985
TI  - Correlation study of two methods for evaluating corneal endothelial damage in
      vitro: the Janus green photometry technique versus cell counting.
AB  - Counting of endothelial cells after vital staining is a time-consuming method
      which, in addition, requires considerable experience and does not normally allow
      for the study of the entire endothelial cell surface. However, the Janus green
      photometry technique (JGPT) is an objective, time- and personnel-saving procedure
      which also has the advantage of allowing for the evaluation of the whole
      endothelial cell surface. A comparative simultaneous experimental study of the
      two methods had not been reported. Freshly excised pig corneas (n = 58) were
      preserved in MK storage medium for 4, 7, 14 and 20 days at 4 degrees C. All
      corneas were stained with Janus green and alizarin red. A 7-mm corneal button
      corresponding to an endothelial surface of 38.46 mm2 was punched out. The
      percentage of damaged cells was determined with cell counting (CC) and with JGPT,
      and the results were statistically compared. Two methods for CC were used. Cells
      were counted either directly under the microscope or in photomicrographs. The
      overall correlation between the results of CC and JGPT was R = 0.98. However,
      when endothelial cell damage was higher than 30%, CC became an estimation by
      approximation, since necrotic areas were confluent, whereas with JGPT the results
      were usable even when the damage was 100%. Thus it appears that although the two
      methods can be used interchangeably, JGPT may in some instances be the method of
      choice.

PMID- 8538986
TI  - Corneal autofluorescence and epithelial barrier function in diabetic patients.
AB  - Corneal autofluorescence and corneal epithelial barrier function of 146 diabetic
      patients and 121 controls were examined using anterior segment fluorophotometry.
      Corneal autofluorescence in diabetic patients was significantly higher when
      compared with that of controls (14.6 +/- 3.7 vs. 10.9 +/- 2.7 ng/ml, p < 0.001),
      and was increased in patients with more severe diabetic retinopathy (r = 0.23, p
      = 0.005), higher postprandial blood glucose level (r = 0.25, p = 0.009), and
      higher glycosylated hemoglobin (r = 0.21, p = 0.047). No correlation existed
      between corneal autofluorescence and the duration of diabetes mellitus. The
      corneal fluorescein concentration 45 min after topical application of 20
      microliters of 2% sodium fluorescein was also significantly higher in diabetics
      than in controls (1,373.2 +/- 1,081.5 vs. 363.0 +/- 308.3 ng/ml, p < 0.001). No
      correlation existed with postprandial blood sugar (r = -0.19, p = 0.056) nor with
      glycosylated hemoglobin (r = -0.13, p = 0.20). The corneas in diabetics became
      more hypesthetic with longer duration of diabetes mellitus (r = -0.19, p = 0.02),
      although the mean corneal sensitivity threshold was not statistically higher in
      the diabetic group (p = 0.57). There was no correlation of the epithelial barrier
      function with the duration of diabetes (r = -0.07, p = 0.38), the severity of
      diabetic retinopathy (r = 0.07, p = 0.38), and the corneal sensitivity threshold
      (r = -0.06, p = 0.43).

PMID- 8538987
TI  - Rapid morphological reorganization of the rabbit corneal endothelium after acute
      exposure to sodium lactate in vitro.
AB  - Corneal stroma-endothelial preparations from 2-kg albino rabbits were incubated
      in vitro in a bicarbonate-Ringer solution equilibrated with 5% CO2-9% O2 over 4 h
      in half-chambers at 37 degrees C. An average net fluid pump activity of 6.8
      microliters/h was measured in the 4th hour. If such preparations were initially
      equilibrated with bicarbonate-Ringer for 90 min and then challenged for 20 min
      with 15 mM sodium lactate or NaCl, an osmotically induced increase in fluid flow
      occurred. After removal of the challenge and return to bicarbonate-Ringer for 2.5
      h, the net fluid pump returned to baseline and then increased again (to an
      average of 9.7 microliters/h) for the lactate- but not NaCl-challenged
      endothelia. Scanning electron microscopy showed that lactate-challenged (but not
      the control or NaCl-challenged) endothelial contained a moderate number of very
      large pleomorphic cells within an otherwise regular mosaic. It is proposed that
      the large cells develop as a result of cell fusion (coalescence).

PMID- 8538988
TI  - Changes in light scattering intensity of the transparent lenses of subjects
      selected from population-based surveys depending on age: analysis through
      Scheimpflug images.
AB  - The physiological ageing changes of decreasing lens transparency were objectively
      evaluated in a total of 1,040 eyes selected from 1,685 individuals who were the
      subjects of population-based cataract epidemiological surveys performed in three
      climatically different survey fields in Japan. The lens transparency changes were
      evaluated from the light scattering intensity on thirteen different lens layers
      seen in slit images taken by the latest type of Scheimpflug camera. The mean
      percentage prevalence of cataracts in all the epidemiological survey subjects
      including grading from I to III, which was also judged objectively through
      documented images, was 64.6% in the Noto subjects, 46.6% in the Hokkaido subjects
      and 38.0% in the Okinawa subjects. The lens transparency at all of the measuring
      points decreased with ageing. The above changes, seen in the lenses of subjects
      in their 40s to 60s, were obviously more prominent compared with those seen in
      subjects in their 40s. Although there were some differences in transparency
      decrease with ageing among the subjects of the three areas, the authors
      tentatively propose to show the data obtained from the Noto subjects as
      representative of Japanese individuals. Lens transparency changes on each lens
      layer showed characteristic ageing changes and those of the representative four
      layers showed an exponential decrease in transparency. The decreasing ratio might
      accelerate from age as early as the mid-40s.

PMID- 8538989
TI  - Type IV collagen in the basement membrane of the corneal epithelium after alkali
      burns in guinea pigs.
AB  - To investigate the changes in the corneal epithelial basement membrane following
      an alkali burn, we examined the immunolocalization of type IV collagen and
      laminin in the eye of the guinea pig burned with alkali. The burn damaged the
      corneal, limbal and conjunctival epithelium. After regeneration, basement
      membrane was interrupted, as indicated by laminin immunoreactivity. Type IV
      collagen immunoreactivity was transiently expressed in the early healing phase in
      the epithelial derived from both the cornea and conjunctiva, but was not seen in
      the normal corneal epithelial basement membrane. Later in the healing process,
      following transdifferentiation of the conjunctival epithelium into a cornea-like
      epithelium, its type IV collagen immunoreactivity was weaker than that in the
      basement membrane of the nontransdifferentiated epithelium. Conjunctival
      transdifferentiation during healing may have led to transient development of type
      IV collagen immunoreactivity.

PMID- 8538990
TI  - Antioxidant therapy in the treatment of experimental acute corneal inflammation.
AB  - To ascertain the effectiveness of topical antioxidant therapy on acute corneal
      inflammation, we have studied the effectiveness of topical treatment with a
      saline solution and with antioxidants such as 0.2% superoxide dismutase and 0.5%
      dimethylthiourea (DMTU) in a controlled experimental study. The evolution of the
      inflammatory process was evaluated by a multimodel approach, including computer
      assisted planimetry of the corneal ulcer and infiltrate, ultrasonic pachymetry,
      luminol-amplified chemiluminescence and the study of corneal transparency by
      direct spectral spectrophotometry transmittance. The experimental model was a
      corneal ulcer created by a 60-second application of 1 N sodium hydroxide. Topical
      treatment with DMTU was shown to significantly improve all parameters tested,
      while superoxide dismutase reduced only the corneal ulcers. Antioxidant topical
      therapy with DMTU was shown to be efficient in reducing the inflammatory reaction
      that occurs during acute corneal inflammation. This suggests that antioxidant
      therapy could be considered as a complementary treatment in the pharmacological
      modulation of acute corneal inflammation.

PMID- 8538991
TI  - Influence of bFGF as a potent growth stimulator and TGF-beta as a growth
      regulator on scleral chondrocytes and scleral fibroblasts in vitro.
AB  - We investigated the proliferation of scleral cells in response to several growth
      factors in vitro to elucidate the mechanism of scleral growth in visual
      deprivation myopia. Scleral chondrocytes and scleral fibroblasts were cultured
      separately in 24-well culture dishes. The number of plated cells was counted
      after the addition of basic fibroblast growth factor (bFGF), transforming growth
      factor alpha (TGF-alpha), TGF-beta, insulin-like growth factor I (IGF-I), IGF-II,
      platelet-derived growth factor AA (PDGF-AA), PDGF-AB and PDGF-BB. All the growth
      factors studied, except for PDGF-AA, stimulated the proliferation of both scleral
      chondrocytes and scleral fibroblasts. bFGF showed the highest effect. TGF-beta
      caused morphologic changes in both scleral chondrocytes and scleral fibroblasts.
      Various growth factors stimulated the proliferation of scleral chondrocytes and
      scleral fibroblasts in a similar manner. bFGF was a potent growth stimulator and
      TGF-beta was suggested to be a growth regulator on scleral chondrocytes and
      scleral fibroblasts.

PMID- 8538992
TI  - Inhibition of platelet-activating factor-induced retinal impairments by cholera
      and pertussis toxins.
AB  - Platelet-activating factor (PAF) has been shown to alter the trans-retinal
      potential recorded from light-stimulated isolated retina. In the present study,
      we investigated the effect of cholera and pertussis toxins on PAF-induced
      impairment of the electroretinogram (ERG). Administered alone, 2 x 10(-7) M PAF
      induced a very marked and rapid drop in the b-wave amplitude. When 75
      micrograms/l of cholera toxin was coadministered with PAF in the perfusion
      solution, no b-wave drop was observed, suggesting that the effect of PAF on
      retinal function was mediated by GTP-binding protein (G protein). Similarly, a
      low dose of pertussis toxin (5 micrograms/l) was sufficient to antagonize the
      action of PAF on the ERG. Our results suggest that the irreversible and
      deleterious effect of PAF on ERG is mediated by a G protein mechanism, located in
      the neural retina.

PMID- 8538993
TI  - Ultrastructural study of basal lamina of retinal pigment epithelium.
AB  - The ultrastructure of basal lamina (BL) of retinal pigment epithelium (RPE) in
      guinea pigs was studied by the quick-freezing, deep-etching (QF-DE) method. The
      retinal tissue was quickly frozen, fractured and deeply etched. A replica was
      prepared by shadowing with platinum and carbon. Electron micrographs of the BL of
      RPE provide a three-dimensional (3-D) ultrastructure. The lamina lucida was
      filled with traversing filamentous structures, which connected the basal
      infolding of RPE with the lamina densa. The lamina densa consisted of a 3-D
      meshwork structure. It is suggested that the traversing filamentous structures in
      the lamina lucida might play a role in anchoring the basal infolding of RPE and
      in maintaining the normal architecture.

PMID- 8538994
TI  - Circadian rhythm of intraocular pressure: a rat model.
AB  - The purpose of this study was to examine whether there is a circadian rhythm of
      intraocular pressure (IOP) in the Lewis rat. Therefore, 20 Lewis rats (40 eyes)
      were subjected to an alternating 12-hour-light and 12-hour-dark cycle. Using a
      Tono-Pen 1, IOP was measured every 2 h between 6 a.m. and 12 midnight and every 3
      h between 12 midnight and 6 a.m. for 2 consecutive days. These measurements in
      the Lewis rat revealed a reproducible circadian rhythm with a peak at 8 p.m. and
      a trough at 6 a.m. In conclusion, when using the Lewis rat as an animal model in
      longitudinal studies that involve the IOP, the IOP should be measured at the same
      time each day to correct for diurnal variations. Additionally, Lewis rats may be
      a useful model to study the causes of circadian rhythms of IOP and for
      pharmacologic studies of new glaucoma medications.

PMID- 8538995
TI  - Pattern electroretinogram in treated ocular hypertension: a cross-sectional study
      after timolol maleate therapy.
AB  - To investigate pattern electroretinogram changes in treated ocular hypertension,
      we evaluated pattern electroretinogram recordings of 48 hypertensive eyes
      following an 8-month timolol maleate therapy. During treatment, 27 of 48 eyes had
      normalized intraocular pressures (15-18 mm Hg), while 21 retained elevated values
      (21-25 mm Hg). Twenty-eight eyes with untreated hypertension (22-25 mm Hg)
      lasting at least 8 months, as well as 32 untreated, normotensive eyes served as
      controls. When compared to untreated normotensive controls, timolol-treated eyes
      with either elevated or normalized intraocular pressures showed reductions in the
      mean electroretinographic amplitudes. However, these amplitude reductions were
      substantially greater in treated eyes with elevated pressures as compared to
      those with normalized ones. Untreated hypertensive controls showed pattern
      electroretinogram reductions, with respect to normal values, that were comparable
      to those of treated hypertensive eyes, but larger than those of treated
      normotensive ones. These results indicate that, in treated ocular hypertension,
      pattern electroretinogram losses tend to be associated with moderately increased
      intraocular pressures in the range of 21-25 mm Hg. Electroretinographic
      abnormalities may be, at least in part, prevented only by lowering intraocular
      pressure into a normal range.

PMID- 8538996
TI  - In vivo morphological changes in rat lenses induced by the administration of
      prednisolone after subliminal X-irradiation. A preliminary report.
AB  - In order to induce steroid cataracts in rat lenses, prednisolone acetate was
      administered together with a single subliminal dose of X-irradiation, which was
      applied unilaterally before steroid application started. The rats were divided
      into a control group (without prednisolone acetate administration), a group with
      a topically administered daily dose of 1 mg/kg prednisolone acetate suspension
      and a group with a systemically applied daily dose of 0.8-1.0 mg/kg prednisolone
      acetate suspension. Changes in the lens were objectively evaluated with in vivo
      Scheimpflug slit images during a 30-week period. Although body weight increase
      was significantly affected in both groups administered prednisolone, animals
      survived until the end of the observation period. The initial changes in the lens
      were the dissociation of the Y-suture and a slight increase in scattering light
      intensity at the posterior embryonic nucleus after both topical and systemic
      steroid administration.

PMID- 8538997
TI  - Morphological and biochemical changes in lenses of guinea pigs after vitamin-C
      deficient diet and UV-B radiation.
AB  - The effect of ultraviolet B (UV-B) radiation and a vitamin-C-deficient (VCD) diet
      on guinea pig lenses was investigated. The initial lens changes in the VCD group
      were observed by slit-lamp examination 6 weeks after the start of the VCD
      treatment; after 12 weeks the changes in the posterior subcapsular region became
      more prominent, and the dissociation around the posterior suture became wider and
      slightly deeper toward the posterior cortex. The high concentration of lens
      oxidized glutathione (GSSG), and the low ratio of reduced glutathione (GSH) to
      oxidized glutathione (GSH/GSSG) on the lens posterior region correlated with
      density changes in the corresponding layers as measured by Scheimpflug images
      with linear microdensitometry. It is suggested that the strong oxidative stress
      of the VCD diet caused the damage at the posterior part of the lens. UV-B
      radiation appeared to accelerate cataract progression in lenses that lack vitamin
      C.

PMID- 8538998
TI  - Influence of 17 beta-estradiol and progesterone on rat ocular lens.
AB  - The effect of 17 beta-estradiol and progesterone on ocular lens in rats and
      untreated controls was studied. In the treated lenses, the activity of hexokinase
      and glucose-6-phosphate dehydrogenase remained unchanged. The activity of
      aldolase was increased in 18- and 20-month-old lenses as compared to controls.
      Aldose reductase activity was decreased at the age of 20 months (p < 0.001).
      Structural lens proteins studies by SDS polyacrylamide gel electrophoresis and
      immunodecoration with specific antibodies for crystallines alpha A + alpha B and
      beta + gamma suggest some protective effect in treated animals.

PMID- 8538999
TI  - Cell biological analysis of the human cataractous lens: implication of lens
      epithelial cells in the development of aftercataract.
AB  - Lens epithelial cells (LECs) from 3 patients with congenital cataract aged 2, 4
      and 12 months, respectively, were cultured. The findings were compared with those
      from 26 eyes of 26 patients with senile cataract, with ages ranging from 60 to 89
      years. The significantly higher growth potential of LECs in patients with
      congenital cataract compared to those with senile cataract, seems to be the cause
      of the higher frequency of aftercataract following cataract surgery in infants.

PMID- 8539000
TI  - Detection of proteoglycans in human posterior capsule opacification.
AB  - Using cuprolinic blue staining, we histochemically examined the ultrastructural
      localization of proteoglycans in the fibrous-type human posterior capsule
      opacification. This capsule opacification contained proteoglycans that showed
      positive staining with cuprolinic blue. Many cuprolinic-blue-positive filaments
      were present within the bundles of collagen fibrils, basal lamina-like material
      and basal lamina of proliferated lens epithelial cells. Pretreatment with enzymes
      and nitrous acid revealed that the collagen fibrils contained chondroitin sulfate
      and dermatan sulfate, whereas the basal lamina-like material and basal lamina of
      epithelial cells contained heparan sulfate. These results suggest that
      proteoglycans are one of the components in posterior capsule opacification.

PMID- 8539001
TI  - Inter-ethnic risk ratios for different types of cataract.
AB  - Patients at Moorfields Eye Hospital were divided according to five broad
      geographical areas of origin in four continents, and classified according as they
      had cortical, nuclear, posterior subcapsular cataract or any of their
      combinations. Relative risk ratios and their tolerances were calculated. Risk
      ratios for some types of cataract were inter-related. Ethnic traits appear to be
      more important than climatic conditions.

PMID- 8539002
TI  - Immunocytochemical study of dystrophin-related protein in the rat retina.
AB  - Dystrophin-related protein (DRP) has been reported to exist in the brain, but
      there are no reports describing its existence in the retina. In the present
      study, DRP localization was examined in rat retinas by immunohistochemistry in
      comparison to dystrophin localization. Rat retinas were fixed using
      paraformaldehyde and immunostained with one antidystrophin antibody and two anti
      DPR antibodies. Dystrophin was observed in the outer plexiform layer, but DRP was
      recognized in ganglion cell layer and inner nuclear layer, but not in the outer
      plexiform layer. DRP has been thought to exist under the plasma membrane, but the
      present study clarified that DRP in the retina was localized throughout the
      perikaryon of the neuronal cells. These results suggest that DRP may play a
      distinct role from that of dystrophin in the rat retina.

PMID- 8539003
TI  - Ontogeny of copper-zinc and manganese superoxide dismutase in the developing rat
      retina: immunohistochemical and immunochemical study.
AB  - The localization of copper-zinc and manganese superoxide dismutase (SOD) in the
      developing rat retina was studied immunohistochemically and immunochemically.
      Immunoreactivity to Cu/Zn SOD was observed in the inner limiting membrane, nerve
      fiber layer, ganglion cell layer (GCL) and pigment epithelium on postnatal day
      (P) 7. From P7 to at least 10 weeks, the distribution of Cu/Zn SOD remained
      unchanged in rats. From P15 to P30, the immunoreactivity to Mn SOD appeared in
      the GCL and inner plexiform layer. The distribution of Mn SOD remained unchanged
      between P30 and 10 weeks. Our immunochemical study revealed that the
      concentration of Cu/Zn SOD was higher than that of Mn SOD throughout the
      postnatal period. The differential distributions of Cu/Zn SOD in the developing
      rat retina support the hypothesis that Cu/Zn and Mn SOD play an important role in
      the protection against oxygen free radicals in the different layers of the retina
      throughout development.

PMID- 8539004
TI  - Pattern-reversal visual-evoked response in bull's eye maculopathy associated with
      Stargardt's disease.
AB  - Using steady-state pattern-reversal visual-evoked response (PVER), we studied the
      macular function in patients with bull's eye maculopathy. The results were
      correlated with fluorescein angiography. Study patients with an established (25
      eyes of 14 patients) and a suspected (8 eyes of 4 patients) diagnosis of
      Stargardt's disease with bull's eye maculopathy were divided into group G (good
      vision group: 15 eyes with visual acuity of 20/40 or better) and group P (poor
      vision group: 18 eyes with visual acuity of 20/50 or worse). The diameters of the
      atrophic area and the normal or less affected central area of the bull's eye were
      measured form the fluorescein angiograms. The mean diameter of the central area
      in group G (2.0 degrees) was significantly larger than that in group P (0.6
      degrees; d.f. = 17, p = 0.0227). The PVER amplitudes were reduced in the patient
      groups with all check sizes and the amplitude-check size functions were flat.
      Amplitude differences were observed between the patient groups with the 20'
      checks (d.f. = 17, p = 0.0638), probably due to the difference in the mean
      central diameters (2.0 degrees vs. 0.6 degrees). Patients with a perifoveal
      abnormality can have an abnormal PVER despite relatively good visual acuity. We
      also recorded the PVER in 7 normal controls tested with simulated ring-shaped
      scotomas, the sizes of which matched the mean diameters of the scotomas in the
      patient groups (7.0 degrees x 0.6 degrees and 7.0 degrees x 2.0 degrees). The
      controls also showed markedly reduced responses with all check sizes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8539005
TI  - Biphasic intraocular pressure response to laser irradiation of the iris in
      rabbits.
AB  - The possibility of an acute increase in intraocular pressure (IOP) following
      laser iridotomy is well known. However, little attention has been paid to the
      hypotony after laser irradiation of the iris. We performed this study to evaluate
      the effect of laser irradiation of the iris on the IOP in pigmented rabbits. IOP,
      aqueous flare values, and aqueous prostaglandin E2 levels were measured before
      and 1, 4, 12, and 24 h after argon laser treatment. The IOP showed a prolonged
      reduction for 24 h following an initial transient increase. Flare values and
      aqueous prostaglandin E2 levels reached a peak 1 h after laser treatment,
      followed by a progressive reduction. Argon laser peripheral iridoplasty that can
      separate the iris from the trabecular meshwork by the mechanical force resulting
      from a contraction burn is used sometimes in treating angle-closure glaucoma. Our
      results showed that the laser irradiation of the iris itself can cause ocular
      hypotony, so that this phenomenon may be another explanation of the IOP response
      after peripheral iridoplasty.

PMID- 8539006
TI  - Starkfest Vision and Clinic Science Symposium in honor of Dr. Lawrence W. Stark.
      Berkeley, California, June 24-25, 1994.

PMID- 8539007
TI  - String editing analysis of human visual search.
AB  - Eye movement (EM) data were recorded for human subjects performing a visual
      search task in a stereoscopic computer-generated three-dimensional scene. Each
      experimental run consisted of six presentations: three different object
      placements on a common background (quasi-natural scene) were used and one of the
      placements was repeated three additional times. Raw EM searchpath data were
      linearized, fixation points were defined via a fixation algorithm and, finally,
      strings of fixation region labels were obtained based upon a priori
      regionalization schemes. Use of string editing techniques allowed quantitative
      comparison of the similarity of various searchpaths. Analysis of the similarity
      of searchpaths for each subject, as well as across subjects, led us to conclude
      that presentation of repeated object placements caused each subject to develop a
      partly self-consistent, but idiosyncratic searchpath based upon a spatial model
      for that placement pattern.

PMID- 8539008
TI  - Context effect of common objects on visual processing.
AB  - In previous experiments on visual processing it was shown that correct
      identification of sequentially and simultaneously presented numerals declined as
      the presentation interval was decreased from 50.0 to 16.7 ms/numeral. To
      determine how performance was influenced in context, common everyday objects were
      used in place of the numerals. These objects were grouped into 36 different
      categories with 4 objects per category. An example of a category was fruit:
      apple, banana, pear, pineapple. For all experimental trials, objects (ranging in
      number from one to four) were presented randomly at four possible positions 1.5
      degrees from a central fixation point. In a sequential trial, the objects were
      displayed in succession at different locations for a stimulus onset asynchrony
      (SOA) of either 16.7, 33.3, or 50.0 ms. The masking of a previous object
      coincided with the onset of the object that followed in the sequence. A
      simultaneous trial consisted of 2, 3, or 4 objects presented concurrently. For
      these trials, simultaneous masking occurred at SOA's of 16.7, 33.3, or 50.0 ms.
      For both experimental paradigms, one-half of the trials consisted of objects from
      the same category, and one-half from mixed categories. Results taken from four
      observers showed that performance for all three SOA's was consistently better
      when the objects were related as opposed to when the objects were not for both
      presentation protocols. This lent support to the theory that there was
      simultaneous interaction of top-down and bottom-up processes in visual
      processing. In addition, as was found in the numerals study, performance was
      better when the objects were presented simultaneously as opposed to sequentially.

PMID- 8539009
TI  - Visual search: eye movements and peripheral vision.
AB  - The visual search task allows investigation of the way in which central processes
      can influence the programming of saccadic eye movements. In this paper, a simple
      search task is studied in which a target is presented in a ring-shaped display of
      eight stimuli. The subject is required to locate the target with a saccadic eye
      movement. Targets were colored disks and the task was to search for a target of a
      particular color. Sensory factors (when all nontargets are identical, the target
      stands out) and central factor (prespecification of the target) both contribute
      to search efficiency. When the display contains a double target, saccades
      sometimes land at an intermediate position between the two targets. This shows
      that the signal delivered by the search procedure is not necessarily highly
      localized.

PMID- 8539010
TI  - Short-term adaptation of eye movements in patients with visual hemifield defects
      indicates high level control of human scanpath.
AB  - In continuation of earlier studies, we recorded gaze movements in patients with
      hemianopic visual field defects primarily due to stroke. Use of high resolution
      infrared oculography enabled us to record and analyze a variety of tasks
      including paradigms of visual search, reading, and scanpath eye movements. The
      tasks were recorded several times in sequential order. Through these sequences,
      we observed short-term adaptation, i.e., training effects of eye movement
      strategies to improve the initially deficient results on the side of the blind
      hemifield with respect to the relative difficulty of the specific task. This
      quantitative and statistically confirmed finding adds new evidence for the top
      down control of the human scanpath even in hemianopic patients.

PMID- 8539011
TI  - Distance cues for vertical vergence adaptation.
AB  - Vertical vergence can be trained to respond to vertical and/or horizontal
      conjugate eye position, horizontal vergence, and vertical head tilt. This cross
      coupling is manifest as a vertical phoria aftereffect (monocular vertical
      vergence response) that varies with direction and distance of gaze. The function
      of the spatially dependent adaptation is to maintain the calibration between
      vertical eye alignment and intended placement of the two retinal images.
      Oculomotor adaptation stabilizes our sense of spatial localization and calibrates
      a body-referenced coordinate representation of visual space that is necessary for
      visually guided motor responses. We have tested the possible association of
      vertical phoria adaptation with perceptual cues to distance in the absence of any
      other associated motor activity. During adaptive training, vertical disparity
      vergence was associated with variations of perceptual distance cues (including
      loom, overlap, relative size, and relative motion), oculomotor distance cues
      (horizontal vergence), or a combination of both classes of cues. We observed that
      in a 2-h period the open-loop (monocular) vertical vergence response could not be
      trained to occur as an aftereffect in association with the perceptual cues to
      distance, whereas it could be trained in association with oculomotor cues. We
      conclude that the spatial specificity of vertical vergence aftereffects caused by
      short-term adaptation results from an associated cross-coupling with supranuclear
      sources of oculomotor activity.

PMID- 8539012
TI  - Effects of heterophoria on stereopsis.
AB  - The effects of horizontal heterophoria on Howard-Dolman stereopsis scores were
      investigated in a population of 1765 stereophotogrammetrists with no obvious
      impediment to binocular vision as determined in a vision screening. Exophoria
      over the 1 to 7 delta range showed no systematic and statistically valid effect
      on stereopsis but esophoria did show an effect. In a related population of 1339
      stereophotogrammetrists, subjects with as little as 1 delta (+/- 0.5 delta) of
      vertical heterophoria exhibited a small but statistically significant decrease in
      stereopsis test scores compared to those with vertical orthophoria. Therefore, a
      heterophoria had different effects on stereoacuity depending on whether it was in
      the exo, eso, or vertical direction. An explanation for the difference is
      proposed using the known dependence of heterophoria and stereoacuity on fixation
      disparity.

PMID- 8539013
TI  - Relation between backward masking deficits and smooth pursuit dysfunction in
      schizophrenia?
AB  - Backward masking deficit and smooth pursuit dysfunction are cognitive,
      information processing markers associated with schizophrenia. In schizophrenia,
      backward masking is typically manifest as a longer interstimulus interval over
      which a mask is still effective in interfering with the processing of a preceding
      target. Smooth pursuit dysfunction is characterized by saccadic smooth pursuit,
      saccadic intrusions, and low-gain pursuit. Although the natures of the two
      markers relative to schizophrenia are somewhat different (e.g., smooth pursuit
      dysfunction is a genetic marker; backward masking is associated more strongly
      with negative symptoms, poor prognosis schizophrenia), information processing
      theory indicates a possible neurocognitive relation between the two.

PMID- 8539014
TI  - Effect of target proximity on transient myopia induced by equidioptric stimuli.
AB  - Transient myopia may be exhibited after sustained focus on a near target. This
      appears to be related to the within-task accommodative response. Although
      proximally induced accommodation has been shown to produce considerable transient
      myopia under open-loop conditions, its effect under naturalistic closed-loop
      conditions remains unclear. Accordingly, the present study examined the effect of
      target distance on transient myopia for equidioptric stimuli (5 D). A Canon R-1
      autorefractor was used to assess the pre- and post-task refractive state
      objectively. Two tasks were performed monocularly and consisted of either
      accommodating on a near target at 20 cm (5 D) or a far target at 6 m viewed
      through a -5 D lens. The former task involved both blur and proximally induced
      accommodation, whereas the latter consisted of a blur stimulus only. Similar
      amounts of transient myopia were found under both conditions. These equivalent
      responses may be related to the relatively small output of proximally induced
      accommodation believed to be present under closed-loop conditions.

PMID- 8539015
TI  - Abnormal transient myopia in symptomatic individuals after sustained nearwork.
AB  - After a sustained period of nearwork, some patients report slightly blurred
      distance vision for several seconds or even minutes. This presumed large and
      prolonged "abnormal transient myopia" has never been objectively documented. A
      Canon R-1 infrared autorefractor was used to assess distance refractive state
      every 2 s before and immediately after a binocular near task in three such
      individuals. Results showed a large post-task myopic shift, slowed baseline
      decay, and increased response variability as compared with that found in
      asymptomatic visually normal individuals. These findings suggested that this
      transient distance blur was related to the increased transient myopia resulting
      from one or more possible abnormalities related to the accommodative system.

PMID- 8539017
TI  - L. Stark bibliography (1952-1994).

PMID- 8539016
TI  - The "Expected Visual Outcome" (EVO) model: methodology and clinical validation.
AB  - PROBLEM: If changes are made to the optics of the eye (e.g., intraocular lens
      implants, contact lenses, etc.) how will they affect performance on clinical
      tests of vision? METHOD: A phenomenological method is presented based on in vitro
      optical transfer function (OTF) and a simple model of human threshold detection.
      RESULTS: The model is used to predict and the results are compared with clinical
      data (acuity, contrast sensitivity) obtained from pseudophakic patients implanted
      with a multifocal intraocular lens (IOL). A good qualitative agreement is found
      with the clinical data. SIGNIFICANCE: This model predicts the relative change in
      clinical performance for a given change in the optical components of the human
      eye. This simple phenomenological model permits numerical prediction of clinical
      tests and is easily calculable.

PMID- 8539018
TI  - Goldmann field testing in glaucoma.

PMID- 8539019
TI  - Recognition of TNO stereotest figures in the absence of true stereopsis.

PMID- 8539020
TI  - Colors of maximal saturation.
AB  - The spectrum locus on the CIE Chromaticity Diagram represents monochromatic
      stimuli which have been exposed to a dark adapted fovea. Some of these colors can
      be made to appear more saturated by chromatic adaptation. The colors both inside
      the spectrum locus and the supersaturated colors outside are bounded by a four
      sided boundary line which constitutes the locus of colors of maximal saturation.
      An attempt has been made to show how this quadrilateral is related to the
      fundamental colors and to a zone theory of color vision.

PMID- 8539021
TI  - Scoring the Farnsworth-Munsell 100-hue for vocational guidance.
AB  - BACKGROUND: We considered whether the color discrimination of mild color
      defectives scoring < or = 100 is the same as that of normals. METHODS: We
      analyzed the FM 100-hue results of 126 normals and 94 congenital color defectives
      retrospectively by considering the Total Error Score (TES) and individual cap
      errors (error profiles). RESULTS: A TES of 100 passes 95% of normals and 24% of
      congenital color defectives. The error profiles of some of the mild defectives
      who pass show abnormal peaks along a red-green axis. An error > or = 5 in these
      regions is a good indicator of abnormal color discrimination. CONCLUSIONS: Some
      30% of mild defectives (TES < or = 100) have limited hue discrimination in the
      red-green domain, so both the TES and error profiles need to be considered when
      providing vocational guidance.

PMID- 8539022
TI  - Dapiprazole's effect upon accommodative recovery: is it due entirely to changes
      in depth of field?
AB  - We conducted a study to evaluate the ability of dapiprazole 0.5% ophthalmic
      solution to reverse accommodative loss brought about by mydriatic drugs having
      mild cycloplegic effects. To accomplish this, we analyzed data from several
      earlier randomized, masked clinical studies. Our composite data include over 90
      subjects dilated with tropicamide. Tropicamide was used alone in 1%
      concentration, as well as in combination with phenylephrine, 2.5% and in the
      proprietary preparation, Paremyd (Allergan Pharmaceuticals). Accommodative
      amplitude and pupillary diameter were measured before instilling dilating drops
      and then again one-half hour later, immediately before instilling either
      dapiprazole or a placebo. Accommodative amplitude and pupil diameter measurements
      were then repeated four more times, on both the treatment and control eyes and at
      30, 60, 120, and 180 min after instillation of the last drop of dapiprazole or
      placebo. We found accelerated "accommodative" recovery with dapiprazole for each
      of the three tropicamide-containing drugs used in our study. This is not
      surprising because some recovery of accommodative amplitude after dapiprazole's
      administration is expected. This is because dapiprazole accelerates pupillary
      recovery and a narrowing of the pupil gives rise to an increase in ocular depth
      of field. Rate of accommodative recovery with dapiprazole was found not to be
      significantly different for all three tropicamide-containing preparations tested
      (p > 0.05). Does dapiprazole produce improvement in amplitude of accommodation
      beyond that attributable to increased depth of field?(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8539023
TI  - Normal values of ocular protrusion in Saudi Arabian male children.
AB  - The extent of ocular protrusion from the orbit is an important sign in the
      diagnosis and management of ocular and orbital diseases. Ocular protrusion is
      dependent, among other factors, on ethnic origin, age, gender, high refractive
      error, axial length, inter outer orbital distance (IOOD), and interpupillary
      distance (IPD). The purpose of this study was to provide normal absolute and
      relative ocular protrusion values for Saudi Arabian male children of Arab origin
      and to furnish regression equations relating ocular protrusion to age, IOOD, and
      IPD. A cross-sectional study was designed and ocular protrusion and IOOD were
      measured using a Hertel prism exophthalmometer. The IPD was measured by using a
      corneal reflection pupillometer. The data were analyzed using t-test and analysis
      of variance tests. The average absolute ocular protrusion of the right and left
      eye was 15.4 mm +/- 1.6 and 15.2 mm +/- 1.6, respectively. The maximum difference
      in protrusion between the eyes was 2.0 mm. Saudi Arabian male children of Arab
      origin who have ocular protrusion values outside the 95% confidence intervals
      should be advised to undergo additional diagnostic tests. A relative ocular
      protrusion value greater than 2.0 mm may be indicative of unilateral proptosis
      among these subjects. On the average, Arab children have more ocular protrusion
      than Caucasians but less than Chinese children.

PMID- 8539024
TI  - Statistical procedures for impact resistance testing at increased drop-ball
      heights.
AB  - PURPOSE: Impact resistance testing of prescription eyewear and nonprescription
      sunglasses is normally performed at a drop-ball height of 50 in (1.27 m). This
      paper presents a statistics-based testing method that uses increased drop-ball
      heights. METHODS: Impact resistance values for glass and plastic lens materials
      were obtained from the available literature. These values were used to determine
      the characteristics of marginal quality and high quality batches of lenses.
      Impact resistance testing procedures were then developed that accepted these
      batches at low and high probabilities, respectively. RESULTS: A large number of
      test parameter combinations met the requirements of the impact resistance testing
      procedure. In general, increasing the drop-ball test height decreased the sample
      size needed to demonstrate that a batch of lenses was impact resistant.
      CONCLUSIONS: Impact resistance testing at increased drop-ball heights is an
      alternative to traditional statistics-based testing procedures. Sample size can
      be smaller, and equipment is relatively inexpensive and readily available.

PMID- 8539025
TI  - Is there a difference in dental caries between myopic and nonmyopic children?
AB  - A number of authors have reported that myopia is associated with high amounts of
      dental caries. Collagen is a major constituent of dentine and it is possible that
      the association between myopia and dental caries is a sign of a common collagen
      defect. Dental caries was quantified in an unselected sample of 9-year-old Hong
      Kong Chinese children, of whom 22 were subsequently classified as myopic and 80
      as nonmyopic. Dental and refractive examinations were carried out independently
      of each other. No association was found between the presence of dental caries and
      the refractive state of the eye.

PMID- 8539026
TI  - Repeatability of subjective and objective refraction.
AB  - Although several studies have examined the repeatability of objective refraction,
      data concerning the repeatability of subjective refraction under masked
      conditions, i.e., where the examiner is unaware of the refractive results, are
      limited. Accordingly, the present study compared the variability of both
      subjective and objective refractive techniques. Refractive error was measured in
      12 subjects on 5 separate occasions. Conventional subjective procedures were
      used, with the exception that the sphere power scale on the phoropter was covered
      so that the examiner was unaware of the final result. Objective measurements were
      obtained using a Canon Autoref R-1 infrared autorefractor. The standard deviation
      (SD) of the five examinations was calculated for each individual and the mean
      values for the population sample determined. The mean SD's for the subjective and
      objective techniques were +/- 0.14 and +/- 0.18 D, indicating 95% confidence
      limits of +/- 0.27 and +/- 0.35 D, respectively. It is concluded that with either
      assessment technique, a change in refractive error of at least +/- 0.50 D should
      be adopted as the minimum significant shift in refractive status.

PMID- 8539027
TI  - Comparison of fixation disparity curve variables measured with the Sheedy
      Disparometer and the Wesson Fixation Disparity Card.
AB  - BACKGROUND: Previous studies suggest differences in the fixation disparity curves
      obtained with the Sheedy Disparometer and the Wesson Fixation Disparity Card, the
      two most commonly used methods for measuring fixation disparity. In one study the
      investigators proposed that the differences do not exist for subgroups divided by
      phoria. The purpose of this paper is to try to clarify this issue by use of two
      large sets of data. METHODS: Dissociated phorias were measured by the von Graefe
      method. Fixation disparity curves were plotted using the Disparometer and the
      Wesson card. RESULTS: Type I fixation disparity curves were most common with the
      Wesson card. Type II curves were found more often with the Disparometer than with
      the Wesson card. The x-intercepts were shifted in the base-in (BI) direction with
      the Wesson card compared to the Disparometer. The y-intercepts were shifted in
      the exo direction with the Wesson card compared to the Disparometer. The
      differences were statistically significant regardless of whether the dissociated
      phoria was exo or eso. The slope of the fixation disparity curve was steeper with
      the Wesson card than with the Disparometer. The difference was statistically
      significant for exophores but not for esophores. The differences between results
      obtained with the two instruments are not consistent from one subject to another
      as shown by high standard deviations of the differences. CONCLUSIONS: The
      fixation disparity curves measured with these two instruments are different.
      Fixation disparity parameters obtained from one of these instruments cannot be
      used with normative findings from the other.

PMID- 8539028
TI  - Optometry admission interviewing practices in Canada and United States.
AB  - This study of optometry programs in Canada and the United States identified both
      the extent of and approach to admission interviewing as well as the reasons for
      its inclusion or exclusion. A written questionnaire was designed, piloted, and
      revised before it was sent to each of the 18 optometry programs. The 15 (83%)
      completed questionnaires were analyzed and discussed in terms of comparisons with
      similar surveys of medical and dental programs. Evidence in the psychology
      literature was presented about the strengths and limitations of this selection
      tool. Eighty percent of the optometry programs that responded provided admission
      interviews. Concerns about interview reliability, validity, and costs precluded
      its use by 20% of the responding programs. Of four variables, the interview was
      the third most important variable in admission decisions. Unlike medical and
      dental programs, optometry programs frequently used a panel format; an approach
      which is recommended in the psychology literature. Similar to surveys of dental
      and medical programs, the reliability and validity of optometry admission
      interviews were likely reduced by insufficient interviewer training and interview
      structure. A need for greater program evaluation of the optometry interview
      process as well as dissemination of the results was indicated.

PMID- 8539029
TI  - Paired-ion extraction and high-performance liquid chromatographic determination
      of diminazene in cattle plasma: a modified method.
AB  - The high-performance liquid chromatographic method published by Aliu & Odegaard
      (1983) was found to give poor peak separation when used to determine plasma
      diminazene concentrations in cattle. Before bioequivalence studies could be
      carried out, the method had to be modified. Solid-phase extraction with
      acetonitrile/0.025 M Na-octane sulphonate and 2% acetic acid as eluent, followed
      by sample concentration, gave recoveries of > 90% for diminazene and the internal
      standard. A mobile phase of acetonitrile/0,005 M Na-octane sulphonate, 0.1%
      triethylamine, pH 3.2 with acetic acid on a Nova Pak C18 column was used for the
      analysis. Wavelength switching was used to determine the internal standard
      (imidocarb) and diminazene at their respective wavelengths of maximum absorbance,
      resulting in a fivefold increase in the limit of detection for diminazene. The
      modified method attained a detection limit of 2 ng.m.-1 (peak 4x baseline noise),
      limit of quantitation of 10 ng.m.-1 (coefficient of variation < 15%) and an
      accuracy of > 96% over the range from 10-5000 ng.m.-1.

PMID- 8539030
TI  - Reactions to heartwater vaccination in crossbred Zebu cattle.
AB  - One thousand and ninety-four crossbred Zebu cattle were immunized against
      heartwater with a sheep-blood vaccine containing the Ball 3 strain of Cowdria
      ruminantium. Animals experiencing febrile reactions were treated at various
      stages of the reaction with tetracycline. Four hundred and sixty-two (42.2%)
      reacted, six (0.6%) of which died. Deaths were significantly less frequent in
      cattle treated on the first day of reaction (2/323, 0.6%) than those treated at a
      later stage (4/61, 6,6%). The mean incubation period was 15,6 d (range 7-23 d).
      Incubation period and frequency of reactions varied significantly between farms,
      between vaccine batches and between vaccine doses. Variations in frequency of
      reactions, incubation period and severity of reaction did not affect the efficacy
      of immunization, as assessed by seroconversion.

PMID- 8539031
TI  - A rapid method to determine bacterial contamination on hatching eggs. 2.
      Correlation of the optical-density measurements after incubation to bacterial
      counts on hatching eggs.
AB  - The suitability of using optical-density (OD) measurements after a 6-h incubation
      period to determine bacterial contamination on hatching eggs was evaluated. A
      total of 154 hatching eggs, from five different flocks, were examined visually
      and bacterial counts and OD measurements of egg washings after 6 h of incubation
      at 37 degrees C were carried out to determine the levels of bacterial
      contamination, and these results were compared. A relationship between the OD
      measurements of egg washings and the log of the bacterial plate counts, was
      demonstrated. The OD measurements provide accurate and quantitative information
      to detect bacterial contamination on hatching eggs, as they are simple to
      perform, repeatable and reliable.

PMID- 8539032
TI  - A rapid method to determine bacterial contamination on hatching eggs. 3. Use of
      commercial DNA probe kits for detection of specific pathogens after six hours of
      incubation.
AB  - The usefulness of commercially available DNA probe kits for the detection of
      Escherichia coli and Salmonella spp. after only 6 h of incubation, was
      determined. It was established that the commercially available probe kits used
      could detect E. coli at initial levels of approximately 4.5 x 10(2) colony
      forming units (cfu) per ml after only 6 h of incubation in nutrient broth (NB).
      Initial bacterial levels as low as 4.5 x 10(1) cfu/ml could be detected when the
      NB was incubated for 18 h. Salmonella Enteritidis, at initial levels of 2.86 x
      10(2) cfu/ml could be detected after 6 h of incubation at 37 degrees C in NB,
      while initial levels as low as 2.86 x 10(-1) cfu/ml could be detected after 18 h
      at 37 degrees C in both NB and selected media, as specified by the manufacturers
      of the probe kits. Commercially available DNA probe kits can therefore be used to
      detect specific pathogens on the surface of hatching eggs and these probes can be
      used in conjunction with an egg-washing system, which is used to determine total
      bacterial contamination, although a longer incubation period greatly improves the
      sensitivity of these tests.

PMID- 8539033
TI  - Canine ehrlichiosis in Egypt: sero-epidemiological survey.
AB  - A total of 374 dogs, 252 from five military kennels and 122 privately owned, were
      tested for Ehrlichia canis antibody. Sera were tested at a 1:20 dilution by
      indirect fluorescent antibody with the use of E. canis cell-culture antigen
      slides. The overall prevalence of E. canis antibody was 33%. Antibody prevalence
      among military dogs (29%) was significantly lower than among privately owned dogs
      (41%; P < 0.05). The E. canis seroprevalence among dogs infested with ticks
      (Rhipicephalus sanguineus) was higher (44%) than that among uninfested dogs (31%;
      P = 0.08). The seroprevalence among military dogs varied from 21-46% at the five
      kennels; lower prevalences were observed in kennels with higher sanitary and
      hygienic conditions. Age- and sex-related E. canis antibody prevalences were not
      significantly different among military and privately owned dogs, although adult
      and male privately owned dogs had the highest seroprevalences (45% and 44%,
      respectively). Three dogs with epistaxis had E. canis antibody titres > 1:320.
      These data demonstrate the first laboratory evidence of E. canis infection among
      dogs in Egypt.

PMID- 8539034
TI  - Mycoplasma-associated polyarthritis in farmed crocodiles (Crocodylus niloticus)
      in Zimbabwe.
AB  - Outbreaks of polyarthritis in farmed crocodiles (Crocodylus niloticus) on five
      farms in Zimbabwe are described. Cases were reported only among the rearing stock
      aged 1-3 years. No breeding stock suffered. Morbidity was about 10% and the
      mortality even lower. All the sick animals consistently displayed swollen limb
      joints as well as progressive lameness and paresis. The synovial structures in
      subacute cases contained mycoplasmas and excess turbid mucus which, at a later
      stage of the disease, became yellowish, inspissated and sterile. Cellular changes
      in the joint capsule included oedema, necrosis of the superficial layers of
      membrane, lymphocytic infiltration and fibrosis. Evidence of pneumonia was
      observed only at necropsies. Fifteen isolates of Mycoplasma were cultured from
      the clinical specimens collected from the four sick and three dead crocodiles.
      The affected joints of all these animals yielded Mycoplasma in pure culture, but
      the culture from lungs yielded post-mortem invaders also. The sick animals were
      treated with a single intramuscular injection of long-acting tetracycline (10
      mg/kg), and oxytetracycline mixed in feed at 550 mg/kg was fed for 10 d. The
      treatment appeared to be effective in ameliorating the clinical signs, but in
      some cases inflammatory swelling persisted. All 15 the isolates conformed to the
      characteristics of the genus Mycoplasma, and were serologically indistinguishable
      in growth-inhibition (Gl) tests. Although these isolates shared the main
      biochemical characteristics of Mycoplasma capricolum, they differed
      serologically. Also goats were refractory to experimental infection with
      crocodile strains. In crocodile yearlings, however, the disease was reproduced
      with an isolate from one of the affected farms. The source of infection remained
      elusive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539035
TI  - Cardiomyopathy of ruminants induced by the litter of poultry fed on rations
      containing the ionophore antibiotic, maduramicin. II. Macropathology and
      histopathology.
AB  - This report contains an account of the gross and histopathological lesions of 20
      cattle and four sheep in 15 field outbreaks of poultry litter toxicity, one steer
      fed ad lib. and six sheep dosed with toxic poultry litter, and ten sheep fed
      experimental rations containing c 2,5 ppm and 5 ppm maduramicin. The principle
      macroscopic lesions in most cattle that died in field outbreaks were indicative
      of congestive heart failure. The lesions in sheep were similar, but generally
      milder. Cardiac dilatation was observed in both sheep and cattle.
      Microscopically, the cardiac lesions were more pronounced in cattle and comprised
      varying degrees of atrophy, hypertrophy, degeneration, necrosis of myocardial
      fibres, and interstitial fibrosis. Skeletal muscle lesions were usually more
      severe in sheep, particularly in the muscles of the hindquarters which appeared
      pale, oedematous and mottled. One of the sheep in the poultry litter dosing trial
      developed signs of congestive heart failure and the hearts of two others were
      dilated. Extensive hypertrophy and atrophy of myocardial fibres were evident in
      the steer fed ad lib. with this material. As in field cases, the myocardial
      lesions of the sheep were less severe than those of the steer. Mild cardiac
      dilatation was present in four of the seven sheep in the maduramicin feeding
      trial. Diffuse hypertrophy of myocardial nuclei was present in all seven cases,
      myocardial fibre atrophy in six, multifocal fibrosis and necrosis in six and two
      cases, respectively, and focal endocardial thickening in two. The skeletal
      muscles revealed granular degeneration and foci of necrosis and regeneration. The
      cardiac and skeletal lesions in the field outbreaks, poultry litter feeding
      trials and maduramicin feeding trials, were highly comparable. This suggests that
      this form of poultry litter intoxication is a chronic form of ionophore toxicity
      the pathology of which is characterized by a dilated cardiomyopathy with
      congestive heart failure and mild (cattle) to severe (sheep) skeletal muscle
      lesions.

PMID- 8539036
TI  - A survey of the Culicoides (Diptera: Ceratopogonidae) of the Umlalazi Nature
      Reserve in Zululand, South Africa, with notes on two species biting man.
AB  - Culicoides biting midges were intermittently collected between July 1988 and
      December 1992 in the Umlalazi Nature. Reserve on the subtropical eastern coastal
      margin of South Africa. Altogether 34 species were collected in a diversity of
      habitats that included a mangrove community, dune forest and mixed thornveld.
      Most Culicoides were collected with the aid of light traps and whilst biting man.
      The pupae of ten species were collected from substrata in an open salt marsh, as
      well as from fresh and stagnant groundwater situations. It was the first time
      that the pupae of six of these ten species were collected. Of the species
      collected in light traps, the two most abundant species, C. leucostictus Kieffer
      (49.1% of 16,563 identified) and C. rhizophorensis Khamala & Kettle (22.3%), were
      also the two species found biting man. The larval habitat of C. leucostictus was
      widespread except in the more saline, tidal areas, but that of C. rhizophorensis
      appeared to be restricted to the tidal salt-march area. Two of the species
      collected, C. fulvithorax Austen and C. moreli Clastrier, are new records for
      South Africa.

PMID- 8539037
TI  - Evaluation of some reproductive parameters in the indigenous boar of Zimbabwe.
AB  - A number of reproductive parameters were evaluated in 12 adult indigenous boars.
      The seminal vesicles, prostate and bulbourethral glands had masses of 184.41 +/-
      18.00 g, 16.69 +/- 2.42 g and 142.05 +/- 16.12 g, respectively, while the penile
      length measured 45.71 +/- 4.49 cm. The testes and epididymides had masses of
      211.82 +/- 26.74 g and 108.81 +/- 11.49 g. The number of sperm averaged 2.78 +/-
      0.59 x 10(9) in the testes and 11.76 +/- 2.11 x 10(9) in the epididymides. The
      daily sperm production per gram (DSPG) of testicular tissue and the daily sperm
      production rate (DSP) were calculated to be 2.98 +/- 0.31 x 10(6) and 0.62 +/-
      0.14 x 10(9) spermatozoa, respectively. The serum level of testosterone measured
      11.98 +/- 0.81 ng/ml. These values suggest a reduced reproductive capacity in
      these animals. However, appropriate selection techniques may be evolved to
      upgrade this indigenous stock while nutrition and management may be improved to
      increase body size, and hence, gonadal development.

PMID- 8539038
TI  - Cryopreservation of sheathed third-stage larvae of Gaigeria pachyscelis (Sandveld
      hookworm).
AB  - A technique for the cryopreservation of third stage larvae of Gaigeria
      pachyscelis is described. It consists of incubating sheathed third-stage larvae
      in 80% (v/v) ethylene glycol as a cryoprotectant for 30 s at 0 degrees C, prior
      to transfer into liquid nitrogen. The survival rate, as assessed by motility, was
      37.6% after 30 d cryopreservation. A sheep infected percutaneously with 700 live
      cryopreserved third-stage larvae, harboured 41 adult worms (infectivity rate:
      5.8%) when necropsied 78 d later.

PMID- 8539039
TI  - The prevalence of intestinal Salmonella infection in horses submitted for
      necropsy.
AB  - Specimens from the ileum, colon and rectum were aseptically collected from 50
      consecutive horse carcases submitted for necropsy to the Department of Pathology,
      Faculty of Veterinary Science, University of Pretoria. These were
      bacteriologically examined for the presence of Salmonella. Seventeen of these
      were positive for Salmonella at one or more sites. Serotyping of the isolates
      revealed a dominance of Salmonella Hayindogo in these horses.

PMID- 8539040
TI  - Overview and classification of spinal infections.
AB  - Hematogenous spread is the most common cause for vertebral osteomyelitis. S.
      aureus is the most common organism in pyogenic vertebral osteomyelitis.
      Hematogenous osteomyelitis is common among diabetics and intravenous drug
      abusers. Tuberculous spondylitis remains common worldwide. In general, vertebral
      body infections not responding to antibiotic treatment and those creating
      unacceptable deformity or neurologic compromise require debridement via an
      anterior approach with strut grafting. Posterior infections are almost always
      postsurgical and require posterior irrigation and debridement in addition to
      antibiotics. Abscesses within the canal require antibiotics and surgical
      debridement especially when neurologic symptoms are present. Infections within
      the canal are approached posteriorly unless the pathology involves the anterior
      spine. Use of metal fixation within the site of an adequately debrided spinal
      infection is controversial but necessary on rare occasions. Posterior fixation
      for anterior infections is preferred. Much has been written about spinal
      infections and their treatment. Landmark articles and additional comprehensive
      sources on spinal infections have been included in the references.

PMID- 8539041
TI  - Wound infections in reconstructive spine surgery.
AB  - The development of a wound infection following reconstructive spine surgery
      depends on a multitude of factors. Although the diagnosis is often difficult,
      prompt recognition of the infection through appropriate testing is vital.
      Diagnosis should result in aggressive, surgical treatment combined with systemic
      antibiotics. Ultimately, though, the best treatment is prevention.

PMID- 8539042
TI  - Pediatric spinal infections.
AB  - A high index of suspicion for spinal infection and an appropriate and prompt
      diagnosis are essential for the treatment of pediatric spinal infections. A 3
      week course of antibiotics and supportive therapy is effective in the majority of
      cases of discitis, the most common pediatric spinal infection. Patients who are
      not toxic may be treated with bracing, or with casting alone in many cases.
      Neurologic deficit or a failure to respond to early treatment requires more
      aggressive measures, including biopsy or surgical debridement. It is essential to
      diagnose rare but serious conditions such as epidural abscess, tuberculosis, or
      opportunistic infections in patients at risk. The authors stress that clinical
      evaluation and appropriate diagnosis are critical for prevention of permanent
      neurologic damage or late bony deformity.

PMID- 8539043
TI  - Neurosurgical care of spinal epidural, subdural, and intramedullary abscesses and
      arachnoiditis.
AB  - Epidural abscess of the spinal column is a rare but potentially devastating
      disease. When recognized early and treated appropriately, the outcome can be
      excellent. Abscesses in the spinal subdural space or in the spinal cord proper
      are even more unusual but can also lead to complete and irreversible loss of
      neurologic function if not diagnosed and treated rapidly. Although infection
      frequently can result in arachnoiditis, there are other more common causes, such
      as surgery and chemical irritants. It remains a difficult condition to treat, and
      long-term therapeutic results are mediocre. Newer technology with spinal cord
      stimulation seems to show improved results but pain relief is incomplete, and the
      percentage of patients with poor results remains high.

PMID- 8539044
TI  - Wound management in spinal infection.
AB  - Wound management in the spine-infected patient is a complex problem. Treatment is
      determined by the primary diagnosis, which may have bearing on wound healing. The
      most common site of wounds requiring plastic surgical intervention in the
      neurologically intact patient is in the posterior thoracic area. In spinal cord
      injured patients, the most common site is in the lumbosacral area. The cause of
      these wounds are iatrogenic because of infection after attempted thoracic fusion
      in the first case. In the spinal cord-injured patient it is caused either by
      postoperative infection or extension of a pressure ulcer in the area of insensate
      skin. Preoperative preparation is a prerequisite before wound closure. Muscle and
      myocutaneous flaps represent the best options in managing these complex wounds.

PMID- 8539045
TI  - The diagnosis of infections of the spine by modern imaging techniques.
AB  - MR image scanning is the most sensitive and specific imaging modality to diagnose
      infection of the spine. The infected disc and adjacent vertebral end plates will
      show increased water signal owing to the infection. The diagnosis of infection of
      the spine and the differentiation between infection and lesions simulating
      infection is described.

PMID- 8539046
TI  - Use of tissue expanders for wound closure of spinal infections or dehiscence.
AB  - Posterior spinal incisions that are made through skin and have been compromised
      by radiation or prior incisions can be difficult to obtain stable closure. In
      addition, if a wound has developed a postoperative infection or wound dehiscence
      caused by poor wound healing, severe complications can develop. The technique of
      expanding adjacent normal skin with implantable tissue expanders has been used in
      select cases with success. The techniques and indications for tissue expansion in
      posterior lumbar wounds is reviewed and several case reports presented.

PMID- 8539047
TI  - Cost of medical care for postoperative spinal infections.
AB  - The movement towards managed care has raised the awareness of health care costs
      in today's society. The additional expense involved in treating patients with
      deep postoperative spinal infections after lower back fusion increases the total
      cost of care more than four times. Three areas of greatest increase in cost are
      room and board, pharmacy and laboratory charges. Decreasing the expense of this
      complication can best be effected through use of home nursing care, choice, and
      duration of antibiotic treatment and prudent laboratory testing.

PMID- 8539048
TI  - Minimally invasive surgical techniques to treat spine infections.
AB  - Minimally invasive techniques including closed laparoscopy and thoracoscopy as
      well as video-assisted procedures using limited open incisions provide an
      excellent alternative for treating vertebral osteomyelitis and tuberculous
      infections in the thoracic and lumbar spine. The traditional principles of
      surgical debridement and a stable interbody fusion are unchanged when applying
      endoscopic techniques. In the future, the spinal endoscopist will have available
      a larger selection of endoscopic instruments, more sophisticated video
      technology, and the development of anterior instrumentation systems to allow for
      rigid internal fixation. These advances, along with the surgeon's endoscopic
      experience and refined techniques, will further establish minimally invasive
      surgical techniques in the field of spinal surgery.

PMID- 8539049
TI  - Outcome assessment in spinal infections.
AB  - The importance of outcome studies in patients undergoing spinal surgery is
      discussed. There are numerous questionnaires used to assess quality of life
      results in orthopedic patients. This suggests disagreement and difficulty in the
      assessing and comparing outcomes. Several of these instruments for assessing
      outcome are reviewed. Postoperative spinal infection can prolong a patients
      recovery from spinal surgery and exacerbate symptoms of lower back pain. A review
      of the authors' patients at 3 years follow-up suggests that outcome with
      postoperative infections was similar to other patients with low back pain
      undergoing fusion without postoperative infectious complications.

PMID- 8539050
TI  - Nutritional status in the patient with spinal infection.
AB  - Patients that undergo spinal reconstructive surgery are nutritionally at risk.
      The elderly, the chronically ill, and the developmentally disabled are often
      malnourished preoperatively. Those patients undergoing combined or staged
      anterior and posterior procedures often become malnourished in the postoperative
      period. Poor nutritional status is unequivocally associated with increased
      postoperative complications, including infectious complications. Close attention
      should be paid to the perioperative nutritional status of these patients and
      strong consideration given to preoperative and postoperative nutritional
      supplementation when indicated.

PMID- 8539051
TI  - Spinal infections in the immunocompromised host.
AB  - There is an increasing population of immunocompromised patients with HIV, IV drug
      abuse, organ transplantation, and long-term steroid treatment developing spinal
      infections. Delayed diagnosis because of blunted host immune response and lack of
      outward signs and symptoms places the treating physician at a disadvantage in the
      treatment of this type of disease, which presents at a later stage of
      development. Immunocompromised patients are infected by a different group of
      pathogens than their healthier cohorts (e.g., Pseudomonas, gram-negative bacteria
      and fungal infections) because their host defenses are diminished. Osteomyelitis
      with or with out pyomyositis and epidural abscess may occur. The overriding
      symptom is back pain. Radiculopathy, myelopathy, and sensory loss may accompany
      local pain and tenderness. Plain film radiography, CT scan, MR image, and bone
      scan is invaluable in the diagnosis of these infections. The cornerstone of
      treatment is identification of the responsible pathogen, appropriate medical
      therapy, immobilization of the affected segment of the spine, and physical
      therapy to combat physical deconditioning. Psoas abscesses may require surgical
      debridement if they cannot be adequately drained by CT-guided percutaneous
      catheterization. Epidural abscesses with neurologic compromise require surgical
      drainage. Impingement of the spinal cord or cauda equina by collapsed
      osteomyelitic vertebral bodies requires surgical debridement by anterior
      vertebrectomy, with an autologous tricortical iliac crest strut and
      immobilization of the spine using external bracing or posterior instrumentation
      as dictated by the disease.

PMID- 8539052
TI  - The use of antibiotics for wound prophylaxis in spinal surgery.
AB  - The principle of spinal surgery prophylaxis is to prevent naturally occurring
      organisms from infecting a sterile site. Avoiding infection is the most important
      concern in decreasing morbidity in the immediate perioperative period.
      Prophylactic cephalosporin is mandatory. Suction drains should be used until
      output is minimal. This lessons the chance of hematoma formation. Hematomas are
      excellent culture media and may result in seromas. Aspiration of seromas that are
      painful can lead to another source of possible infection. The efficacy of topical
      irrigants in preventing infections during lumbar spine surgery remains to be
      answered.

PMID- 8539053
TI  - Cervical spine infections.
AB  - Cervical spine infections arise from a variety of etiologies including
      postsurgical, iatrogenic, and hematogenous routes. Clinical history, physical
      examinations, and diagnostic studies all play an integral role in the diagnosis
      and treatment of these infections. Successful treatment depends on a proper and
      timely diagnosis, understanding the etiology, and defining the extent to which
      the infectious process involves the spinal supporting and neurologic elements.
      Surgical treatment is required when there is abscess formation, instability,
      progressive kyphosis secondary to vertebral body collapse, or canal compromise
      with neurologic deficits.

PMID- 8539055
TI  - Perioperative risk factors for wound infections after lower back fusions.
AB  - Although reduced by technology, antibiotics and surgical technique, spinal
      infection from surgery remains a recognizable risk. The rate of infection in
      spinal surgery is reviewed. Identification of risk factors are important in
      preoperative planning. Preoperative risk factors for postoperative spinal
      infection include obesity and smoking. Attention to sterility and efficient
      technique can reduce potential wound contamination intraoperatively. Excessive
      wound drainage and seroma formation should warn of a potential wound infection.

PMID- 8539054
TI  - Thoracolumbar infections in penetrating injuries to the spine.
AB  - A detailed review of the TJUH experience and the published literature on gunshot
      and stab wounds to the spine has been presented. The following statements are
      supported. (1) Military (high-velocity) gunshot wounds are distinct entities, and
      the management of these injuries cannot be carried over to civilian (low
      velocity) handgun wounds. (2) Gunshot wounds with a resultant neurologic deficit
      are much more common than stab wounds and carry a worse prognosis. (3) Spinal
      infections are rare following a penetrating wound of the spine and a high index
      of suspicion is needed to detect them. (4) Extraspinal infections (septic
      complications) are much more common than spinal infections following a gunshot or
      stab wound to the spine. (5) Steroids are of no use in gunshot wounds to the
      spine. In fact, there was an increased incidence of spinal and extraspinal
      infections without a difference in neurologic outcome compared with those who did
      not receive steroids. (6) Spinal surgery is rarely indicated in the management of
      penetrating wounds of the spine. The recommendations for treatment at TJUH of
      victims of gunshot or stab wounds with a resultant neurologic deficit are as
      follows. (1) Spine surgery is indicated for progressive neurologic deficits and
      persistent cerebrospinal fluid leaks (particularly if meningitis is present),
      although these situations rarely occur. (2) Consider spine surgery for incomplete
      neurologic deficits with radiographic evidence of neural compression.
      Particularly in the cauda equina region, these surgeries may be technically
      demanding because of frequent dural violations and nerve root
      injuries/extrusions. These cases must be evaluated in an individual case-by-case
      manner. The neurologic outcomes of patients with incomplete neurologic deficits
      at TJUH who underwent acute spine surgery (usually for neural compression
      secondary to a bullet) were worse than the outcomes for the patients who did not
      have spine surgery. A selection bias against the patients undergoing spine
      surgery was likely present as these patients had evidence of ongoing neural
      compression. (3) A high index of suspicion is necessary to detect spinal and
      extraspinal infections. (4) Do not use glucorticoid steroids for gunshot wound
      victims. (5) Conservative (nonoperative) treatment with intravenous broad
      spectrum antibiotics and tetanus prophylaxis is the sole therapy indicated in the
      majority of patients who sustain a penetrating wound to the thoracic or lumbar
      spines.

PMID- 8539056
TI  - Pyogenic vertebral osteomyelitis and postsurgical disc space infections.
AB  - The presentation and clinical course for hematogenous vertebral osteomyelitis and
      postoperative discitis is presented. The treatment is primarily conservative care
      in the form of immobilization and parenteral antibiotics. The indications for
      surgery are rare and should be reserved for patients resistant to treatment or
      with septic course, abscess formation, or neurologic deficits. In these cases,
      the infectious process has generally involved the adjacent vertebrae or the
      neural elements. Surgery usually involves an anterior approach. The principles of
      surgical treatment involve debridement of necrotic tissue, decompression of
      neural elements, and stabilization of the spine. The outcome of patients with
      vertebral osteomyelitis and secondary discitis in general is favorable when
      appropriate treatment is rendered. Extension of the infection to the spinal canal
      in the form of an epidural abscess is also reviewed.

PMID- 8539057
TI  - Microbiology and antimicrobial therapy of spinal infections.
AB  - Hematogenous vertebral osteomyelitis is almost always a monomicrobial infection
      affecting predominantly the older population. S. aureus is the most common micro
      organism isolated. Gram-negative bacilli, however, are seen primarily in elderly
      males with the urinary tract as the source of infection, as well as in IVDA. In
      the latter group, P. aeruginosa, as well as S. aureus, are the dominant
      microorganisms. The offending organisms are generally isolated by needle biopsy,
      using a cutting needle, or by open surgical biopsy when necessary. Spinal
      epidural abscesses have very similar microbiology. Antimicrobial therapy is
      generally given parenterally in high doses, together with surgical evacuation of
      abscesses and debridement of necrotic tissue, when necessary. Therapy may be
      guided by the ESR. In VO, when the patient is doing clinically well and the ESR
      decreases to at least half of the pretherapy value, therapy may be stopped, but
      continued elevation of the ESR and the presence of abscesses may necessitate more
      prolonged therapy. The role of oral antimicrobial therapy is currently unclear.

PMID- 8539058
TI  - Tuberculosis of the spine.
AB  - Chemotherapeutic agents remain the cornerstone of treatment for spinal
      tuberculosis. The arguments that surgery is necessary for biopsy and to allow for
      removal of infection and its byproducts have been usurped by advanced biopsy
      techniques and trials demonstrating resolution of infection and most abscesses
      using chemotherapy. Although chemotherapy alone has been demonstrated to be
      effective for some neurologic deficits, those lesions that may be safely treated
      without surgery remain to be fully defined. Modern imaging techniques have
      allowed more precise diagnosis and identification of neural compression and the
      extent of bony involvement. Refinement and popularization of anterior surgical
      techniques have made decompression and reconstruction relatively safe in
      experienced hands. Lesions that possess a propensity towards kyphosis are more
      readily identifiable. The use of instrumentation in the face of active disease
      appears to be promising, though at present there is a relative paucity of
      supporting data. Despite these advances in treatment, it must be borne in mind
      that ultimately, the diagnosis of this relatively uncommon disorder must precede
      the treatment.

PMID- 8539059
TI  - [Immunologic studies in chronic urticaria].
AB  - Chronic urticaria is considered to be a heterogeneous disease, which can be
      divided into several subclasses. The authors investigated 126 patients suffering
      from chronic urticaria with 41 of unknown origin. The aim of the present study
      was to work out a strategy for the complete investigation of patients with
      chronic urticaria. The findings of the immunological study modified the results
      obtained by medical assessment of the 126 chronic urticaria cases, diminished the
      number of the patient with chronic urticaria unknown etiology.

PMID- 8539060
TI  - [Effect of pancreas transplantation on triglyceride metabolism].
AB  - Transplantation of pancreatic gland with systemic venous drainage of the graft
      causes elevated plasma levels of insulin. To examine lipid metabolism
      triglyceride clearance capacity, lipolytic enzymes, plasma lipids and
      lipoproteins were quantified in pancreas-kidney transplant recipients and
      compared them to lipid parameters of healthy controls and those of patients who
      had received only kidney transplants. Eleven pancreas-kidney transplant
      recipients with type I diabetes, 9 non-diabetic kidney transplant recipients as
      controls for the effects of immunosuppressive medication, and 11 healthy controls
      were studied. In pancreas-kidney transplant recipients fasting cholesterol, non
      HDL cholesterol, triglyceride levels were found 5.5 (+/- 1.0), 3.4 (+/- 0.78) and
      1.06 (+/- 0.29) respectively and expressed in mmol/L (mean +/- SE). The results
      were statistically not different from those of healthy controls. In contrast, non
      diabetic kidney transplant recipients cholesterol, non-HDL cholesterol and
      triglyceride levels were increased to 6.1 (+/- 0.81) (p < 0.05), 4.6 (+/- 1.1) (p
      < 0.05) and 2.34 (+/- 1.53) mmol/L (p < 0.05). HDL cholesterol averaged 2.08 (+/-
      0.36) in pancreas-kidney transplant recipients, clearly higher than that of
      kidney transplant recipients 1.53 (+/- 0.39) mmol/L (p > 0.01), or of controls
      1.61 (+/- 0.37) mmol/L (p < 0.05). In pancreas-kidney transplant recipients
      postprandial lipaemia was the lowest and lipase activity was the highest compared
      both to kidney transplant recipients (p < 0.001, p < 0.05) and controls (p <
      0.01, p < 0.05). This excellent triglyceride clearing capacity appears to be the
      result of a high activity of lipoprotein lipase, which, can be explained by the
      peripheral hyperinsulinaemia.

PMID- 8539061
TI  - [Evaluation of hearing loss by means of inner ear acoustic emission in neonates
      treated with aminoglycoside].
AB  - Despite their ototoxic and other side effects, aminoglycosides are still widely
      used in the treatment of neonatal infections. A novel method for evaluation of
      hearing loss is distortion product otoacoustic emission (DPOAE). Physiologic
      acoustic energy-emission produced by sound stimulus in the inner ear is detected
      by DPOAE. Existing acoustic emission indicates the functional integrity of the
      inner ear. DPOAE was performed in 19 newborns treated with netilmicin for
      different infections. Serum netilmicin levels did not exceed 12 mg/l; renal
      functions were normal. Existence of emission was detected in 15 newborns. There
      was no emission found in 4 newborns unilaterally, which was fully restored in 2
      months. In conclusion, aminoglycosides have no considerable ototoxic side
      effects. DPOAE is thought to be an objective, fast, and non-invasive method for
      hearing screening in the newborn period.

PMID- 8539062
TI  - [Practical questions about organizing a gynecologic outpatient clinic for
      climacteric-osteoporosis patients].
AB  - The author established a climacteric-osteoporosis outpatient clinic at his
      department of obstetrics and gynecology among the first ones in Hungary. On the
      basis obtained with the care of 3000 patients the author outlines the most
      important duties connected with such a clinic. In his opinion it is of special
      importance to screen women with several risk factors for postmenopausal
      osteoporosis,--supply these women at risk with hormone replacement therapy (HRT)
      and to care them,--include diseases which contraindicate HRT before starting it, 
      -work out rational cooperation between the interested specialties and to delimit
      the duties,--make the rules of direction of patients clear,--supply osteoporotic
      women treated by rheumatologists with HRT, --use uniformed diagnostic and
      therapeutical protocol, --inform the women population and to prepare the
      specialists and family doctors and to take part in their further education.
      According to experiences of the author HRT is especially effective to stop
      climacteric complaints and to prevent and treat osteoporosis.

PMID- 8539064
TI  - [Bernat Vas (1864-1930), co-author of the first laboratory manual in Hungary].

PMID- 8539065
TI  - [The fate and diseases of Napoleon].

PMID- 8539063
TI  - [Dysembryoplastic neuroepithelial tumor].
AB  - The dysembryoplastic neuroepithelial tumor is a benign central nervous system
      neoplasm of children and young adults manifesting almost exclusively in complex
      partial seizures. The authors report the case of an 8-year-old boy presenting
      with characteristic clinical and radiologic features who subsequently underwent
      surgery. Light microscopic, immunohistochemical and ultrastructural traits of the
      tumor are described demonstrating pluripotential differentiation of tumor cells
      and architectural features suggesting a dysontogenic lesion. A brief literature
      review on the biology and histologic diagnosis of the dysembryoplastic
      neuroepithelial tumor is provided. Although this uncommon tumor accounts for only
      a minority of intracranial neoplasms, its pathogenetic role has to be considered
      in the differential diagnosis of temporal lobe epilepsies. This is the first
      report on this recently described, rare neoplastic condition in Hungary.

PMID- 8539066
TI  - [Raynaud phenomenon, caused by vibration of a hedge-clipping tool].

PMID- 8539067
TI  - [Azithromycin: from macrolides to azalides].

PMID- 8539068
TI  - [Special issue devoted to azithromycin].

PMID- 8539069
TI  - [Effect of the molecular structure of azithromycin on pharmacokinetics and the
      antimicrobial activity].
AB  - Azithromycin possesses in position 9 of the lactone cycle a nitrogen atom which
      provides a second site of protonation. Hence, and compared to erythromycin,
      azithromycin is more stable in the gastric environment, enjoys improved digestive
      absorption and improved digestive toleration, displays much higher intracellular
      accumulation responsible for prolonged serum and tissue half-lives, which allows
      simplified therapeutic schedules. It is also postulated that improved activity
      against Gram negative isolates such as H. influenzae and B. catarrhalis results
      from the same structural particularities.

PMID- 8539070
TI  - [Azithromycin: critical points].
AB  - The determination of the French breakpoints (< or = c, > C) were selected by the
      use of different criteria including bacteriological, pharmacokinetic and
      obviously clinical criteria. Concerning the bacteriological results,
      azithromycin, being an acid stable orally administered antimicrobial drug, is in
      vitro marginally less active than erythromycin against Gram-positive organisms
      including beta-haemolytic streptococci and Staphylococcus aureus. But in
      contrast, this azalide is more active than erytromycin against many Gram-negative
      pathogens, notably Neisseria gonorrhoeae, H. influenzae, Branhamella (Moraxella)
      catarrhalis, Ureaplasma urealyticum, and Borrelia burgdorferi. The activity of
      azithromycin is unaffected by the inoculum, unlike of pH, serum, and presence of
      CO2 for anaerobes. However, erythromycin-resistant micro-organisms are also
      resistant to azithromycin. Considering the pharmacokinetic criteria and the
      clinical results such as infections of the lower and upper respiratory tracts,
      skin and soft tissues, uncomplicated urethritis/cervicitis associated with N.
      gonorrhoeae, Chlamydia trachomatis or U. urealyticum, the preliminary breakpoints
      of azithromycin are defined by the following concentrations (< or = 0.12 and > 4
      mg/l). Additional experimental and clinical results are required to confirm the
      in vitro activity against some other bacterial species (E. faecalis, L.
      monocytogenes, Brucella, P. multocida, or even Salmonella and Shigella).

PMID- 8539071
TI  - [Azithromycin: tissue pharmacology].
AB  - Among macrolide derivatives, azithromycin which is an azalide, is a totally
      original new drug as to its pharmacokinetics in serum and tissues. Compared to
      reference compounds such as erythromycin or roxithromycin, pharmacokinetic
      parameters of azithromycin are characterized by: (i) much lower serum
      concentrations; (ii) a much longer elimination half-life (48-96 h); (iii) high
      and persistent tissue concentrations. The latter characteristic has been
      demonstrated in animal models (experimental H. influenzae pneumonia in mice) and
      in human studies. In lung parenchyma, azithromycin concentrations were higher and
      more persistent (72 h) in infected mice (12 mg/kg) as compared to non infected
      mice (controls) receiving the same dose of azithromycin (50 mg/kg); this may
      result from high intracellular concentrations in polymorphonuclear leucocytes and
      release of the drug at pulmonary sites of infection. In man, concentrations of
      azithromycin have been measured in lung parenchyma, bronchial secretions,
      tonsils, during exploratory or surgical conditions. After a single dose of 500 mg
      of azithromycin, local levels may reach up to 10 mg/kg with persistence of high
      levels for > or = 72 h in lungs, tonsils, sinus and bronchial secretions (1.5 to
      8.6 mg/kg or mg/l). Five consecutive doses of azithromycin (500 mg per day)
      maintained for 10 days tonsil concentrations higher than the MICs for susceptible
      bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539072
TI  - [Clinical pharmacokinetics of azithromycin].
AB  - The bioavailability of azithromycin is approximately 37%. Concomitant
      administration of oral azithromycin with food significantly decreases by 50% drug
      bioavailability. Following a single oral 500 mg dose, peak plasma concentrations
      of about 0.35-0.45 mg/l are attained within approximately 2 hours. With a 500 mg
      oral dose on day 1, followed by 250 mg daily on days 2 to 5, peak and through
      plasma concentrations on day 5 are around 0.25 and 0.05 mg/l respectively. These
      low plasma concentrations are the consequence of extensive and rapid distribution
      from plasma to tissues. Plasma protein binding is low, less than 50% at plasma
      concentrations obtained with the usual dosage regimen. Apparent volume of
      distribution is very large, 25 to 35 l/kg. Azithromycin is mainly eliminated
      unchanged in the faeces via biliary excretion and transintestinal secretion.
      Urinary excretion is a minor elimination route: about 6% and an oral dose and 12%
      of an intravenous dose are recovered unchanged in urine. The mean terminal
      elimination half-life of azithromycin is 2 to 4 days. The pharmacokinetics of
      azithromycin is not significantly altered in elderly subjects and in patients
      with mild to moderate renal or hepatic insufficiency.

PMID- 8539073
TI  - Azithromycin drug interactions.
AB  - Pre clinical work in vivo and in vitro have suggested that azithromycin has a low
      potential for significant drug interactions. Clinical studies conducted thus far
      have generated results in accordance with the preclinical science [6]. Direct
      comparisons with the most modern macrolides have been published and evidence
      suggests that azithromycin is likely to be associated with fewer significant drug
      interactions. However, as a final point, I wish to point out that proof of an
      absolute negative is not possible and therefore in any patient, on multiple
      medication with adverse findings, a drug interaction should be considered as part
      of the differential diagnosis.

PMID- 8539074
TI  - [Azithromycin, pharmacodynamic evaluation in animal models].
AB  - Several experimental models have been used in order to evaluate the in vivo
      efficacy of azithromycin against numerous human pathogenic bacteria and
      parasites, including comparison between azithromycin and other antibiotics
      belonging or not to the macrolide family. Using the experimental models, three
      major objectives can be distinguished: the comparative studies of the efficacy
      dose 50 (ED50) of azithromycin compared to other orally given antibiotics, the
      azithromycin efficacy in animal infected with intracellular multiplying micro
      organisms, and the demonstration of the specific azithromycin accumulation in
      tissues in direct relationship with the local recruitment of phagocytic cells at
      the infectious foci. The ED50 of azithromycin has been compared with those of
      erythromycin or cefaclor in varying acute murine infections. Evidence was given
      of a similar efficacy for the three tested antibiotics. Nevertheless a marked
      advantage for azithromycin was observed in experimental local infections and with
      infections due to Gram-negative bacteria (Haemophilus influenzae, Branhamella
      catarrhalis). The second objective was to confirm in vivo the preferential
      efficacy of azithromycin in models using intracellular multiplying
      microorganisms, due to its great capacity to accumulate inside of professional
      phagocytes. Several models have been used, such as those performed with Listeria
      monocytogenes, Legionella pneumophila, S. typhimurium, Brucella melitensis, M.
      avium and C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539075
TI  - [The particular case of azalides: antibiotic diapedesis. Experimental data from a
      murine model of pneumococcal pneumonia].
AB  - The relations between the clinical efficacy, phagocytic transport phenomena,
      tissular and sera kinetics have been assessed in a pneumonia murine model. At
      first, the correlation between the clinical efficacy and pharmacokinetics
      characteristics has been studied for the erythromycin, spiramycin, roxithromycin,
      clarithromycin and azithromycin. An in vivo clinical efficacy hierarchy has been
      established (azi > ery > roxi = azi > spira). A hierarchy identical to the
      clinical efficacy, has been recognised for the pulmonary elimination half lives
      and the pulmonar AUC. These could be considered as predictive of these
      antibiotics activity in the respiratory infections. In a second time, the
      tissular pharmacokinetics of the azithromycin in leukopenic mice allowed to
      confirm the leukocytes role in the transport and release of this antibiotic in
      the midst of the infections site. Finally, this antibiotic demonstrated its
      efficacy in a bacterienic infection even when administered at a low dosage thus
      allowing to have sera concentrations identical to those obtained in human
      clinical case and close to MIC's for S. pneumoniae. The pharmacokinetic novelty
      displayed by its strong tissular penetration can explain its remarkable efficacy.

PMID- 8539076
TI  - [Azithromycin: clinical assessment].

PMID- 8539077
TI  - [Use of azithromycin in ORL].
AB  - If the demonstration of the interest to treat beta-haemolytic streptococcal
      pharyngitis is not to be done, the recommended antibiotics, most of the time,
      display the drawback of a treatment with one to three intakes daily for 10 days.
      The azithromycin, with its numerous properties, allows for the required treatment
      duration, to decrease the intakes number, thus facilitating the compliance. Its
      in vitro activity is very good on streptococci with a MIC90 of 0.06 mg/l. Its in
      vivo activity in animal, with experimental Streptococcus pyogenes infection
      models is identical to the amoxicillin activity, and better than those of other
      tested macrolides. One of the major characteristics of azithromycin in man is its
      most peculiar pharmacokinetic with an extended half life and very high tonsillar
      concentrations, for at least 10 days after the administration of the product at
      the 1.5 g dose regimen over 3 days. In streptococcal acute tonsillitis clinical
      studies, with a 1.5 g dose regimen over 5 days, clinical results and bacterial
      eradication are identical to those obtained in the Penicillin V groups. This
      administration facility should greatly improve the treatment compliance and lower
      the risks of a prematurely discontinued treatment.

PMID- 8539078
TI  - [Azithromycin and bronchopulmonary infections].
AB  - Azithromycin is a molecule of the macrolide family, belonging to the azalides
      class. Several of its characteristics allow for its use in the treatment of the
      community-acquired lower respiratory tract infections. Commonly isolated
      pathogens in bronchial infections are most frequently H. influenzae, S.
      pneumoniae, M. catarrhalis, C. pneumoniae and M. pneumoniae, and more rarely or
      in the context of a particular background, S. aureus, Gram negative bacteria and
      L. pneumophila. MIC90 of these germs is generally low or slightly elevated,
      displaying an inhibitory activity of the azithromycin on these bacteria.
      Nevertheless, the frequency of macrolide-resistant S. pneumoniae is not
      negligible and this germ must be considered as inconstantly susceptible to the
      macrolide family. Pharmacokinetics studies evidenced from high to very high
      azithromycin concentrations in the pulmonary tissues, reaching values well above
      MIC of pathogens commonly isolated. Given the long half-life, these
      concentrations persist a long time after oral administration. As azithromycin
      concentrates much in polymorphonuclear leucocytes, they release azithromycin
      after having migrated into the infectious site by chimiotactism, thus allowing to
      increase the antibiotic concentration at infection site. These requirements have
      been confirmed in vivo in animal models and in clinical studies. Two experimental
      models on macrolide susceptible S. pneumoniae, and H. influenzae evidenced a
      better activity of azithromycin in comparison to other macrolides tested against
      these two germs.

PMID- 8539079
TI  - [Azithromycin and genital infections].
AB  - The lower genital tract infections due to Chlamydia trachomatis are frequent,
      essentially occurring in young patients, with possible complications and severe
      sequela, particularly in women where the sterility risk is one of the major
      consequences. If an effective treatment could be systematically proposed, a good
      compliance (easy administration and good toleration) is one of the key factor to
      success. In this context, the azithromycin displays numerous advantages. The
      azithromycin in vitro activity on Chl. trachomatis strains is permanent with MIC
      comprised between 0.06 and 0.125 micrograms/ml, with an activity equivalent to
      those of other macrolides, to tetracyclines and quinolones. Different animal
      models allow to demonstrate the curative activity of the azithromycin
      administered as a single dose, at dosage regimen equivalent to those used in man,
      and a prophylactic activity on the salpingitis onset in provoked Chl. trachomatis
      infections. Several comparative clinical studies with azithromycin administered
      as a 1 g single dose displayed very satisfactory results with 98% of bacterial
      eradication, identical to those obtained with reference treatment. On the other
      hand, restrictions to the product use are a less constant activity against
      Neisseria gonorrhoeae and a lack of efficacy on Mycoplasma hominis. The efficacy
      on Treponema pallidum remains to be clinically tested.

PMID- 8539080
TI  - [Azithromycin: new orientations].

PMID- 8539081
TI  - [Effects of azithromycin on the virulence of Pseudomonas aeruginosa].
AB  - Pseudomonas aeruginosa is a saprophyte opportunistic bacteria which frequently
      colonizes the respiratory tract of patients presenting a severe chronic
      bronchitis pathology. Secreting a number of exotoxins and enzymes inducing an
      inflammation and necrosing of the surrounding tissues, it provokes irreversible
      pulmonary lesions. Different experimental in vitro works evidenced macrolides
      activity on the production and/or secretion of these factors, with a diminution
      of elastase, protease, lecithinase and D-nase synthesis. Among the macrolides,
      azithromycin seems to have the most pronounced activity. In vivo, some patients
      suffering from bronchiolitis or cystic fibrosis have been clinically improved
      with a treatment using erythromycin, or clarithromycin or azithromycin. These
      very preliminary results demand to be confirmed but the macrolides could allow a
      decrease of Pseudomonas aeruginosa pathogenicity and thus stop the deterioration
      of pulmonary functions.

PMID- 8539082
TI  - [Helicobacter pylori and azithromycin].
AB  - Helicobacter pylori is a Gram-negative bacterium with man as the unique reservoir
      and where the niche is the stomach. Transmission between individuals could be by
      fecal and oral route. In the stomach, the bacterium is mainly located at the
      mucus level and adhere to antral cells which are the privileged target. Within
      the colonized mucosa, H. pylori generates or secretes different deleterious
      compounds against the epithelial cells: urease, hydrolyzing urea into ammonia, a
      cytotoxic agent: monochloramine also cytotoxic, various enzymes and a vacuolyzing
      cytotoxin; all of these also contribute to the pathogenic potential. In addition
      the associated inflammatory reaction probably plays a part in the lesion process.
      One important consequence is peptic ulcer disease and particularly duodenal ulcer
      which can further degenerate into a precancer lesion and to a lesser extent some
      dyspeptic syndromes. Bacterial eradication can be obtained by the combination of
      an antisecretory drug with an antibiotic. Macrolides have a good activity against
      this bacterium. The azithromycin MIC50 is 0.12 mg/l. A bactericidal activity is
      observed at concentrations equal or higher than 0.10 mg/l. After a single dose of
      500 mg, azithromycin concentrations are 0.48 micrograms/g in the mucus and 4
      micrograms/g in the gastric tissue. Concentrations persist for a long time, due
      to long half life (3 days). In pilot clinical trials, with a tritherapy combining
      azithromycin with metronidazole and omeprazole, 80% of bacterial eradication was
      obtained. These promising need to be validated by larger clinical trials.

PMID- 8539083
TI  - [New pathogens and mode of action of azithromycin: Toxoplasma gondii].
AB  - Azithromycin can inhibit the growth of Toxoplasma gondii tachyzoites in vitro,
      but the effect is only observed with prolonged incubation with the drug,
      reflecting the delayed mode of action of this macrolide on the parasite.
      Azithromycin is probably acting by inhibition of protein synthesis but the site
      of action and fixation in the parasite has not been demonstrated. Azithromycin is
      also effective against intracystic bradyzoites in vitro, but long term
      administration of azithromycin to chronically infected mice failed to reduce the
      mean number of brain cysts. In models of acute toxoplasmosis, azithromycin was
      found to have a limited effect on brain infection, whereas parasites were cleared
      from blood and lungs of infected mice, resulting in a significant protection of
      treated mice comparatively to untreated controls. When azithromycin is combined
      with pyrimethamine or sulfadiazine, an additive effect is observed in vitro, and
      a remarkable synergistic effect is observed in vivo in the treatment of acute
      toxoplasmosis. Together, these results are in favor of the use of azithromycin in
      combined therapies for the treatment and/or prophylaxis of toxoplasmosis.

PMID- 8539085
TI  - Review of azithromycin activity against Legionella spp.
AB  - Azithromycin is about as active against Legionella spp. in vitro as is
      erythromycin, with modal MICs approximately 0.5 to 0.125 microgram/ml, depending
      on the method used. In contrast, azithromycin is much more active against
      intracellular L. pneumophila than is erythromycin. In a guinea pig model of
      Legionnaires' disease, azithromycin is much more active than is erythromycin or
      clarithromycin. Despite the paucity of reports of treatment of Legionnaires'
      disease with azithromycin, it is likely to be as or more effective than
      erythromycin.

PMID- 8539084
TI  - [Azithromycin and Mycobacterium avium infection].
AB  - Mycobacterium avium infection is a frequent complication during the late stage of
      AIDS. M. avium is resistant or poorly susceptible to classical antituberculosis
      drugs. Some new macrolide antibiotics such as clarithromycin or azithromycin are
      bactericidal against M. avium, and their use has dramatically improved the
      prognosis of this infection. In vitro, azithromycin has MICs against M. avium
      ranging from 4 to 64 MIC50 being 16 mg/l and a MIC90 being 32 mg/l. Despite low
      concentrations in serum, close to 0.4 mg/l, very high intracellular
      concentrations of azithromycin, above the MIC, may be achieved. Azithromycin is
      active in vitro in the model of macrophage infection. Furthermore, azithromycin
      is active against murine experimental infection with M. avium. Clinical studies
      conducted among patients with AIDS have shown that azithromycin was active
      against disseminated M. avium infection, with a dose of 600 mg/d. Ongoing studies
      are designed to better determine the ideal dose, to compare its activity with
      that of clarithromycin and to determine the antibiotics that could be combined to
      prevent the selection of resistant mutants. Other ongoing studies are evaluating
      the efficacy of azithromycin for the chemoprophylaxis of M. avium infection in
      HIV infected patients with a CD4T lymphocyte concentration lower than 100/mm3.

PMID- 8539086
TI  - The incremental priming technique: a method for determining within-condition
      priming effects.
AB  - A novel priming technique is applied in two experiments using an alphabetic
      decision and a lexical decision task to study effects of repetition, and form
      related priming on letter and word recognition. The incremental priming technique
      consists of a gradual increase of the prime's informational value
      (operationalized as prime intensity). The minimum prime-intensity level serves as
      a within-condition baseline for each priming condition. Thus, we can define any
      priming effect with respect to two baseline conditions: one is the minimum
      intensity condition of the particular priming condition (within-condition
      baseline), and the other is a different priming condition (across-condition
      baseline). This double-baseline approach makes measuring of priming effects more
      reliable and imposes stronger constraints on our interpretations of these
      effects.

PMID- 8539087
TI  - Identifying objects from a haptic glance.
AB  - Subjects identified common objects under conditions of a "haptic glance," a brief
      haptic exposure that placed severe spatial and temporal constraints on stimulus
      processing. They received no advance cue, a superordinate-level name as cue, or a
      superordinate and basic-level name as cue. The objects varied in size relative to
      the fingertip and in the most diagnostic attribute, either texture or shape. The
      data suggest that object recognition can occur when global volumetric primitives
      cannot directly be extracted. Even with no cue, confusion errors resembled the
      target object and indicated extraction of material and local shape information,
      which was sufficient to provide accuracy above 20%. Performance improved with
      cuing, and the effect of exposure duration was observed primarily with minimal
      cuing, indicating compensatory effects of top-down processing.

PMID- 8539088
TI  - Facial identity and facial speech processing: familiar faces and voices in the
      McGurk effect.
AB  - An experiment was conducted to investigate the claims made by Bruce and Young
      (1986) for the independence of facial identity and facial speech processing. A
      well-reported phenomenon in audio-visual speech perception--the McGurk effect
      (McGurk & MacDonald, 1976), in which synchronous but conflicting auditory and
      visual phonetic information is presented to subjects--was utilized as a dynamic
      facial speech processing task. An element of facial identity processing was
      introduced into this task by manipulating the faces used for the creation of the
      McGurk-effect stimuli such that (1) they were familiar to some subjects and
      unfamiliar to others, and (2) the faces and voices used were either congruent
      (from the same person) or incongruent (from different people). A comparison was
      made between the different subject groups in their susceptibility to the McGurk
      illusion, and the results show that when the faces and voices are incongruent,
      subjects who are familiar with the faces are less susceptible to McGurk effects
      than those who are unfamiliar with the faces. The results suggest that facial
      identity and facial speech processing are not entirely independent, and these
      findings are discussed in relation to Bruce and Young's (1986) functional model
      of face recognition.

PMID- 8539089
TI  - The interaction of objective and subjective organizations in a localization
      search task.
AB  - We investigated how both objective and subjective organizations affect perceptual
      organization and how this perceptual organization, in turn, influences observers'
      performance in a localization search task. Two groups of observers viewing
      exactly the same stimuli (objective organization) performed in significantly
      different ways, depending on how they were induced to parse the display
      (subjective organization). In Experiments 1 and 2, the observers were asked to
      describe the location of a tilted target among a varying number of vertical or
      horizontal distractors. Subjective organization was induced by instructing
      observers to parse the display into either three horizontal regions (rows) or
      three vertical regions (columns). The position of the target was critical:
      location performance, as assessed by reaction time and errors, was consistently
      impaired at the locations adjacent to the boundaries defining the regions,
      producing what we refer to as the subjective boundary effect. Furthermore, the
      extent of this effect depended on whether the stimulus-driven and conceptually
      driven information concurred or conflicted. This made location information more
      or less accessible. In Experiment 1, the strength of objective grouping was a
      function of the proximity of the items (near or far conditions) and their
      orientation in a 6 x 6 matrix. In Experiment 2, the strength of objective
      grouping was a function of similarity of color (items were color coded by rows or
      by columns) and the orientation of the items in a 9 x 9 matrix. The subjective
      boundary effect was more pronounced when the display promoted grouping in the
      direction orthogonal to that of the task (e.g., when observers parsed by rows but
      vertical distractors were closer together [Experiment 1] or color coded
      [Experiment 2] to induce global columns). In contrast, this effect decreased when
      the direction of both objective and subjective organizations was parallel (e.g.,
      when observers parsed by rows and horizontal distractors were closer together
      [Experiment 1] or were color coded [Experiment 2] to induce global rows). A
      localization search task proved to be an ideal forum in which objective and
      subjective organizations interacted. We discuss how these results indicated that
      observers' performance in a localization task was determined by the interaction
      of objective and subjective organizations, and that the resulting perceptual
      organization constrained coarse location information.

PMID- 8539090
TI  - Visual-auditory interaction in speeded classification: role of stimulus
      difference.
AB  - An experiment examined cross-modal interference and congruence in speeded
      classification: Subjects had to identify compound (visual-auditory) stimuli as
      either low or high in spatial position (visual judgment) or low or high in pitch
      (auditory judgment), in 16 conditions, each of which combined one of four
      possible pairs of tones, varying in frequency difference, with one of four
      possible pairs of dots, varying in positional difference. Both classification by
      position and classification by pitch revealed Garner interference (poorer
      performance than baseline, with orthogonal variation in the irrelevant dimension)
      and congruence effects (better performance with congruent than with incongruent
      stimulus combinations), but pitch classification showed more. Furthermore, the
      size of the pitch difference strongly affected classification by pitch and less
      strongly affected classification by position, but the size of the position
      difference affected neither. The findings are consistent with the view that
      Garner interference and congruence effects are closely related, perhaps arising
      from a common source, and suggest that the asymmetries could depend in part on
      the degree of dimensional overlap between stimuli and responses.

PMID- 8539091
TI  - The box alignment illusion: an orientation illusion induced by pictorial depth.
AB  - In four experiments, observers attempted to align two sets of oblique edges to
      parallel. The contexts for these alignments included lines in isolation (2-D
      control), lines embedded in orthogonal drawings of same-oriented and different
      oriented boxes (3-D objects), and each of these viewed against backgrounds
      depicting strong linear perspective (3-D backgrounds). A consistent distortion
      was observed in the alignments of different-oriented boxes relative to control
      lines, indicating that the parallel lines in these stimuli appeared to diverge
      toward the top of the picture. Furthermore, this box alignment illusion decreased
      with interstimulus distance, whereas alignment distortions in control lines and
      same-oriented boxes increased with distance. Viewing the stimuli against 3-D
      backgrounds produced a dramatic reversal of the illusion, with control lines now
      appearing to converge more than the boxes. These results suggest that the
      illusion reflects basic processes involved in pictorial depth perception.

PMID- 8539092
TI  - Cross-modal slant and curvature matching of stereo- and motion-induced surfaces.
AB  - In many laboratory setups and in many day-to-day situations, a unique solution of
      the structure-from-two-views problem is unobtainable. Yet, when the visual system
      is presented with two projections in a sequence, it nevertheless appears to
      generate a reasonably stable percept of structure. In the research reported here,
      we examined whether the same surface would be perceived when subjects were
      presented with a pair of views that alternated in time monocularly (two-frame
      motion) or were shown simultaneously to both eyes (stereo). In Experiment 1, we
      studied slant perception: human observers were asked to match the slant of a
      motion-induced planar surface with its stereo-induced counterpart. In Experiment
      2, the perceived curvature of parabolic surfaces was matched in a similar way.
      The results show that motion-induced slant is matched with a higher value of the
      stereo-induced slant. However, the curvature experiment showed that motion
      induced curvature is matched with a lower stereo-induced curvature. One possible
      explanation may be that the slant and curvature are internally inconsistent in at
      least one of the modalities.

PMID- 8539093
TI  - Shifts in the perceived location of a blurred edge increase with contrast.
AB  - Perceived brightness is nonlinearly related to luminance. Consequently, any
      mechanism operating on the (transformed) luminance profile of a blurred edge to
      detect its location should make errors, and the magnitude of these errors should
      increase with contrast. The perceived location of a blurred edge was measured at
      a range of contrasts and a range of blur space constants in a vernier alignment
      task. It was found that the perceived location of a blurred edge was affected by
      the contrast and the blur space constant of the edge. At low contrasts, the
      apparent location of the blurred edge was near the calculated location of the
      edge, assuming the linear transduction of luminance. At higher contrasts, the
      perceived location of a blurred edge was shifted toward the dark side of the
      edge, and the shift increased with contrast.

PMID- 8539094
TI  - Vibrotactile masking: the role of response competition.
AB  - When two tactile patterns, a target and a nontarget pattern, are presented in
      close temporal proximity to the same location, the nontarget pattern may
      interfere with the identification of the target. A series of experiments examined
      the extent to which the interference in target identification results from
      masking (interference in the representation of the target at an early stage of
      processing) or from response competition. A response competition view of pattern
      perception holds that both the target and nontarget are fully processed to the
      level of evoking responses. Interference is produced when subjects select the
      nontarget rather than the target. This view was tested with a paradigm developed
      in studies of selective attention. Pairs of tactile patterns were presented to
      subjects' left index fingerpads. The amount of interference produced by a
      nontarget that is physically different from a target depends on whether the
      nontarget is associated with the same response as the target or a different
      response. The amount of masking also depends on the set of target and nontarget
      patterns that are used. The results support the conclusion that subjects have
      available a representation of both the target and the nontarget and that a
      substantial portion of the interference previously attributed to masking may be
      due to response competition.

PMID- 8539095
TI  - Preferential processing of target features in texture segmentation.
AB  - In five experiments, observers were required to detect a texture target and/or
      identify the orientation of elements composing target and nontarget regions. They
      were significantly worse at discerning the orientation of nontarget regions than
      at detecting target presence (Experiment 1). On the other hand, accuracy of
      identifying target orientation was found to be near 100% (Experiment 2). When
      observers were required only to identify surround orientation (Experiment 3),
      accuracy was diminished on target-present trials relative to that on target
      absent trials. The superiority of target processing and the interference produced
      by target presence on surround processing were demonstrated in unpracticed
      observers (Experiment 4). In Experiment 5, it was found that information
      regarding target presence is available before information regarding feature
      values of the target. These findings are consistent with a model of visual
      attention and search that incorporates a fast generalized difference operator and
      a slower feature comparison process.

PMID- 8539096
TI  - Binaural summation after learning psychophysical functions for loudness.
AB  - Do response-related processes affect perceptual processes? Sometimes they may:
      Algom and Marks (1990) produced different loudness exponents by manipulating
      stimulus range, and thereby also modified the rules of loudness summation
      determined by magnitude scaling. The present study manipulated exponents by
      having a dozen subjects learn prescribed power functions with exponents of 0.3,
      0.6, or 1.2 (re sound pressure). Subjects gave magnitude estimates of the
      loudness of binaural signals during training, and of monaural and binaural
      signals after training. During training, subjects' responses followed the nominal
      functions reasonably well. Immediately following training, subjects applied the
      numeric response scales uniformly to binaural and monaural signals alike; the
      implicit monaural-binaural loudness matches, and thus the basic rules underlying
      binaural summation, were unaffected by the exponent learned. Comparison of these
      results with those of Algom and Marks leads us to conclude that changing stimulus
      range likely influences underlying perceptual events, whereas "calibrating" a
      loudness scale through pretraining leaves the perceptual processes unaffected.

PMID- 8539097
TI  - Detectability of duration and intensity increments in melody tones: a partial
      connection between music perception and performance.
AB  - Two experiments demonstrate positional variation in the relative detectability
      of, respectively, local temporal and dynamic perturbations in an isochronous and
      isodynamic sequence of melody tones, played on a computer-controlled piano. This
      variation may reflect listeners' expectations of expressive performance
      microstructure (the top-down hypothesis), or it may be due to psychoacoustic
      (pitch-related) stimulus factors (the bottom-up hypothesis). Percent correct
      scores for increments in tone duration correlated significantly with the average
      timing profile of pianists' expressive performances of the music, as predicted
      specifically by the top-down hypothesis. For intensity increments, the analogous
      perception-performance correlation was weak and the bottom-up factors of relative
      pitch height and/or direction of pitch change accounted for some of the
      perceptual variation. Subjects' musical training increased overall detection
      accuracy but did not affect the positional variation in accuracy scores in either
      experiment. These results are consistent with the top-down hypothesis for timing,
      but they favor the bottom-up hypothesis for dynamics. The perception-performance
      correlation for timing may also be viewed as being due to complex stimulus
      properties such as tonal motion and tension/relaxation that influence performers
      and listeners in similar ways.

PMID- 8539098
TI  - Visual discrimination of local surface depth and orientation.
AB  - Many theoretical analyses of 3-dimensional form perception assume that visible
      surfaces in the environment are perceptually represented in terms of local
      mappings of metric depth and/or orientation. Although this approach is often
      taken for granted in the study of human vision, there have been relatively few
      attempts to demonstrate its psychological validity empirically. In an effort to
      shed new light on this issue, our research has been designed to investigate the
      accuracy with which observers can discriminate metric depth and orientation
      intervals on smoothly curved surfaces. Observers were presented with visual
      images of surfaces defined by shading and/or texture, on which two pairs of
      points were designated with small dots. In Experiment 1, their task was to
      identify which pair of points had a greater difference in depth; in Experiment 2
      they were required to judge which pair had a greater difference in orientation.
      The Weber fractions obtained for these tasks were 10 to 100 times greater than
      those that have been reported for other types of sensory discrimination,
      indicating that the perception of metric structure from these displays is
      surprisingly coarse grained.

PMID- 8539100
TI  - Support for the cue-heuristic model is based on suboptimal observer performance:
      response to Gilden and Proffitt (1994)

PMID- 8539099
TI  - The eccentricity effect: target eccentricity affects performance on conjunction
      searches.
AB  - The serial pattern found for conjunction visual-search tasks has been attributed
      to covert attentional shifts, even though the possible contributions of target
      location have not been considered. To investigate the effect of target location
      on orientation x color conjunction searches, the target's duration and its
      position in the display were manipulated. The display was present either until
      observers responded (Experiment 1), for 104 msec (Experiment 2), or for 62 msec
      (Experiment 3). Target eccentricity critically affected performance: A pronounced
      eccentricity effect was very similar for all three experiments; as eccentricity
      increased, reaction times and errors increased gradually. Furthermore, the set
      size effect became more pronounced as target eccentricity increased, and the
      extent of the eccentricity effect increased for larger set sizes. In addition,
      according to stepwise regressions, target eccentricity as well as its interaction
      with set size were good predictors of performance. We suggest that these findings
      could be explained by spatial-resolution and lateral-inhibition factors. The
      serial self-terminating hypothesis for orientation x color conjunction searches
      was evaluated and rejected. We compared the eccentricity effect as well as the
      extent of the orientation asymmetry in these three conjunction experiments with
      those found in feature experiments (Carrasco & Katz, 1992). The roles of eye
      movements, spatial resolution, and covert attention in the eccentricity effect,
      as well as their implications, are discussed.

PMID- 8539101
TI  - [MR imaging findings of the femoral marrow in myelodysplastic syndrome].
AB  - MR imaging of the femoral marrow was performed in 30 patients with
      myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid
      leukemia (AML). The MRI appearance was classified into five patterns: 1) fatty
      marrow; 2) faint signal; 3) nodular pattern; 4) heterogeneous infiltration; and
      5) diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow
      were evaluated and compared with those in normal subjects as well as in patients
      with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE
      image and a high signal on STIR image, began in the proximal femoral marrow
      almost symmetrically in patients with MDS. The area of abnormal signal intensity
      tended to gradually extend towards the distal portion of the femur as the disease
      progressed. MRI patterns of the femoral marrow correlated with marrow
      cellularity, and diffuse marrow infiltration was noted in patients with a more
      advanced type of MDS or with severe anemia. There were limitations to making an
      accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression
      of the MRI appearance in the course of MDS was thought to be a sign suggesting
      evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic
      anemia, although the nodular pattern was commonly seen in the latter disease.

PMID- 8539102
TI  - [Late phase contrast enhanced-CT analysis of thrombosed type aortic dissection].
AB  - Seven patients with thrombosed type aortic dissection who underwent both early-
      and late-phase contrast enhanced (CE)-CT scans were analyzed. The image
      acquisition of early-phase CE-CT began 30 seconds after the intravenous
      administration of contrast material at an injection rate of 1.5 ml per second.
      Late-phase CE-CT began 6 minutes after contrast material injection. The
      thrombosed false lumens were not enhanced on early-phase CE-CTs in any of the
      cases. In five of seven cases, on the other hand, false lumens of the descending
      aorta were enhanced on late-phase images. Late enhancement in the false lumen was
      roughly divided into two patterns; (1) a crescentic enhancement of the sub
      adventitial region (3 cases), and (2) a vague enhancement around the ulcerlike
      projection (2 cases). The mechanism of late enhancement in the false lumen was
      not fully elucidated. Although the clinical significance of late enhancement has
      not yet been established, it will be useful to demonstrate an unstable status of
      the thrombosed false lumens before organization.

PMID- 8539103
TI  - [Ultrasonography of pediatric right lower abdominal pain: correlation with
      clinical and pathological results].
AB  - Right lower abdominal pain is a common problem in the pediatric population.
      Ultrasonography (US) is a well-accepted imaging modality in the clinical
      management of this problem. One hundred and six consecutive pediatric patients
      with right lower abdominal pain were prospectively evaluated. There were 54 boys
      and 52 girls, with ages ranging from 3 to 15 years (mean: 9.9 years). Final
      diagnoses were established based on pathological findings or clinical follow-up.
      US had sensitivity of 90%, specificity of 98%, and accuracy of 94% in the
      diagnosis of acute appendicitis. Among all true negative cases (n = 55), there
      was a variety of US findings other than appendiceal abnormality in 21 cases
      including intestinal and/or mesenteric (n = 19), gallbladder (n = 1), and ovarian
      (n = 1) abnormalities. All 21 cases were managed medically without complication.
      We conclude that US of pediatric right lower abdominal pain is a reliable imaging
      modality not only for the diagnosis of surgical cases but for eliminating the
      unexpected surgical intervention.

PMID- 8539104
TI  - [CT findings of primary retroperitoneal cystic tumors: special emphasis on the
      distinction benignancy from malignancy].
AB  - We describe the CT findings of primary retroperitoneal cystic tumors in 20
      patients (cystic lymphangioma, 9; cystic teratoma, 3; cystic neurinoma, 4;
      mucinous cystadenocarcinoma, 3; synovial sarcoma, 1). CT findings were
      retrospectively reviewed and the findings correlated with the pathological
      findings to determine malignant or benign cystic tumors. Definite criteria for
      malignancy were invasion to surrounding organ and the presence of distant
      metastasis. However, the sensitivity of these criteria was very low (25%).
      Enhancement of an intracystic solid component was a reliable criterion (p < 0.05)
      for malignancy (sensitivity 75%, specificity 81%, accuracy 80%). Either
      unilocular cystic appearance or the presence of a "neck" (between the cystic mass
      and paraaortic region) strongly suggested the possibility of benignancy
      (specificity 100%). The "neck" was thought to be morphologically specific for
      cystic lymphangioma.

PMID- 8539105
TI  - [Intratumoral LPD deposition within hepatocellular carcinoma without arterial
      tumor staining].
AB  - The dissociation of intratumoral LPD deposition and arterial tumor staining was
      investigated in 20 cases of hepatocellular carcinoma (HCC) without arterial tumor
      staining. The intratumoral deposition of LPD injected from the hepatic artery was
      observed in nine cases of HCC and coincided with the decrease in tumor vascular
      bed evaluated by photomicroscopic study and arterial portography. LPD deposition
      was not observed within the 11 other tumors, which were diagnosed as well
      differentiated HCC. Infusion angiographic CT revealed that the arterial and
      portal vascular beds were separated from each other. Therefore, arterial tumor
      staining was insufficient for accurate evaluation of the tumor vascular bed. The
      vascular bed in cancerous and noncancerous tissue was accurately evaluated by the
      addition of the contrast enhancements from the hepatic artery and the portal
      vein.

PMID- 8539106
TI  - [Ultrasonography for traction injuries of the brachial plexus].
AB  - Results of preoperative ultrasonography (US) were compared with the subsequently
      offered operative findings retrospectively on 35 ventral rami of the cervical
      nerves (11 C5, 11 C6 and 13 C7) in 12 patients injured in motorcycle accidents in
      order to examine the usefulness of US in the diagnosis of nerve injury. The
      findings of a US-scanned ramus consisted of shape, internal echo pattern,
      regularity of border, and ratio of the diameter of an injured nerve to that of
      the corresponding nerve on the intact side (I/C). An intact ventral ramus was
      shown as a hypoechoic tubular structure with many parallel fine linear internal
      echoes, a regular border, and I/C ranging from 1.0 to 1.2. Categories such as I/C
      and shape improved the accuracy of differential diagnosis of severe nerve
      injuries. Avulsion of the ganglion was observed as a winding or tadpole-shaped
      remarkably enlarged (2.3 < or = I/C < or = 5.0) mass lesion, intraforaminal
      lesion as a thick (1.5 < or = I/C < or = 3.2) structure with an irregular shape
      and border close to the transverse process, and pseudocontinuity as irregular
      internal echoes. It was difficult to discriminate a lesion with continuity and
      localized scar formation around the nerve from normal fasciculi. These results
      strongly suggest that the application of improved US diagnosis to cervical nerve
      injury should make it much easier to select the best treatment for the patient,
      in that we can detect preoperatively those injuries to which nerve
      transplantation is not applicable.

PMID- 8539107
TI  - [Clinical usefulness of helical-scanning CT for the evaluation of
      arteriosclerotic carotid lesions].
AB  - We examined arteriosclerotic carotid lesions in 76 patients using helical
      scanning CT (HES-CT), and evaluated the clinical usefulness of this method. A
      high speed slip-ring X-ray CT system was used. Scanning of the neck was performed
      for a 30 second period following intravenous bolus injection of non-ionic
      contrast medium, while couch top movement was 2.0 mm/sec. Multiplannar
      reconstruction images (MPR-image) and 3-dimensional surface images (3D-image)
      were reconstructed from the continuous raw data. MPR-images offered axial,
      coronal and sagittal images in which the lesion could be seen from any direction,
      and 3D-images that could be freely rotated were obtained by using a track ball
      and monitor. Eighteen cases were also evaluated by conventional angiography.
      Excellent HES-CT images were obtained in 73 cases, showing occlusion in 13,
      stenosis in 34, plaques without calcification in 15 and plaques with
      calcification in 74 vessels. A good correlation was obtained between HES-CT and
      angiogram in most cases, and in 6 cases, HES-CT was superior in the detection of
      stenosis, because it enabled us to observe the lesion from various directions.
      These results suggested that HES-CT was a minimally invasive, useful diagnostic
      method for the evaluation of arteriosclerotic carotid disease.

PMID- 8539108
TI  - [Distal pulmonary vessels demonstration by magnetic resonance angiography and its
      usefulness in the diagnosis of peripheral nodules].
AB  - To evaluate the usefulness of MRA in the diagnosis of peripheral pulmonary
      nodules, 18 lung cancers and 12 old inflammatory nodules were studied employing
      multiplanar fast radiofrequency spoiled gradient echo sequence (SPGR) with phased
      array coils. For each case, 12 images in coronal and sagittal sections were
      obtained after administration of Gd-DTPA, and original images, maximum intensity
      projection (MIP) images and multiplanar reconstruction (MPR) images were used for
      the interpretation. In ten cases, MRA images were compared with resected
      specimens and we found that the minimum diameter of pulmonary vessels which could
      be demonstrated by our method was about 1.5mm. As the results of the
      interpretation of MRA images in 30 cases, venous involvement, which is one of the
      classical important findings indicative of malignancy, was clearly demonstrated
      in 15 of 18 (83%) lung cancers, whereas such involvement was detected in only 3
      of 12 (25%) inflammatory nodules. Pulmonary MRA, especially MIP and MPR images
      could make it easy to identify involved vessels, and proved to be useful in
      differentiating pulmonary nodules.

PMID- 8539109
TI  - [Radiotherapy for carcinoma of the esophagus in aged patients].
AB  - One hundred fifty-four patients with esophageal carcinoma were treated with
      either irradiation alone or irradiation combined with surgery at the University
      of Occupational and Environmental Health Hospital between January 1980 and
      February 1992. The number of patients 75 years old and older was 25. In patients
      74 years old and younger, the overall five-year survival rate by Kaplan-Meier
      method was 24.5%. The survival rate was best in the patients who were treated by
      a combination of irradiation and surgery. In patients 75 years old and older, the
      one-year survival rate was 59%, and the three-year rate was 20%. Aged patients
      had a tendency to be worse in performance status, and there was no correlation
      between treatment modality and survival time. We conclude that radiotherapy is
      useful for treating esophageal cancer in aged patients particularly when
      maintenance of the quality of life is considered.

PMID- 8539110
TI  - [Techniques for determining position from more than two radiographs intersecting
      at arbitrary angles in brachytherapy].
AB  - The least squares method and geometrical solution for calculating position were
      used in the two-projection method. Five coordinate systems were defined as a
      normal system, image system on film intersecting the beam central axes at an
      arbitrary angle and the projection, virtual coordinate and virtual image
      coordinate systems with beam central axis as one of the three coordinate axes to
      determine the geometrical relationship between a point and image on the film.
      Normal coordinates of the point were calculated by six geometrical solution sets
      and two forms of the least squares method using the rotation matrixes of the
      coordinate systems. One least squares method solves simultaneous nonlinear
      equations, and the other derives a strict solution from simultaneous linear
      equations. The latter least squares method has little physical meaning and is not
      as useful as the former. Although the former has physical meaning, the iterative
      approximation method should be used to determine position since a strict solution
      cannot be obtained directly. By these least squares methods, position is
      determined with less error using the projections at more than two focal spots.

PMID- 8539111
TI  - [Quantitative image feature analysis of echographic textures using the normalized
      first moment of the power spectra: comparison of normal thyroid with chronic
      thyroiditis].
AB  - In order to evaluate the coarseness of echographic textures objectively,
      ultrasonic B-mode data from the thyroid glands in 10 normal subjects and 10
      patients with chronic thyroiditis were digitized. The normalized first moment of
      the power spectra in the digitized matrix data that were obtained was calculated
      by computer processing of a Fourier transformation algorithm. On phantom study,
      when the location of the region to be analyzed or the gray scale level of the
      images was changed, the normalized first moment of the power spectra in the low
      frequency region of less than 1.0 cycle/mm varied significantly, and noise
      components in the high frequency region of more than 2.5 cycles/mm exceeded the
      signal components. Thus we attempted to calculate the normalized first moment of
      the power spectra from 1.0 to 2.5 cycles/mm in human thyroid glands. The values
      of the normalized first moment of the power spectra in the thyroid glands with
      normal (n = 20) and chronic thyroiditis (n = 20) were 0.989 +/- 0.036 and 1.065
      +/- 0.063, respectively. These values were significantly different between the
      two groups (p < 0.01). It is concluded that the normalized first moment of the
      power spectra calculated within the limited frequency is useful in characterizing
      the echographic texture of chronic thyroiditis.

PMID- 8539112
TI  - [Experimental study on embolic materials for simultaneous segmental embolization
      through transarterial route].
AB  - To determine suitable embolic materials for simultaneous arterioportal
      embolization through the arterial route, transcatheter arterial embolization
      (TAE) using iodized oil (Lipiodol) mixed with monomeric n-butyl-2-cyanoacrylate,
      with absolute ethanol, or mixed with Gelfoam powder was carried out in 14 dogs.
      Following TAE, the distribution of Lipiodol in hepatic artery, peribiliary
      plexus, and portal vein was analyzed by soft tissue x-ray radiography and en bloc
      silver impregnation. As a result, Lipiodol mixed with absolute ethanol, and
      Gelfoam powder was considered to be the most reasonable embolic materials for
      this purpose.

PMID- 8539113
TI  - Nurse-led unity.

PMID- 8539114
TI  - Drying out.

PMID- 8539115
TI  - In the cuckoo's nest.

PMID- 8539116
TI  - What price PREP?

PMID- 8539118
TI  - Caring for confused people in the general hospital setting.

PMID- 8539117
TI  - Can do, can't do?

PMID- 8539119
TI  - Alzheimer's disease and carers.
AB  - This paper is based on the author's impressions of his placement in mental health
      centres in North Lincolnshire. The focus is on the nature of the relationship
      between the older person with dementia and those who care for them--nurses and
      relatives.

PMID- 8539120
TI  - Exclusion zones.

PMID- 8539121
TI  - The named-nurse initiative: what is the point?
AB  - The first two papers in this short series explored different views of the named
      nurse initiative. The first, more sceptical view, questioned the value of the
      initiative for nurses, while the second explored the potential value for
      improving patient care. This paper draws the arguments together and suggests ways
      in which lessons may be learnt that will help nurses make sense of the named
      nurse initiative.

PMID- 8539122
TI  - Risk: the sociological view of perception and management.
AB  - In this final article on sociology we focus on one issue which is central to
      health and health care--risk--and consider the contribution of sociology to an
      understanding of the ways in which risk is perceived and managed.

PMID- 8539123
TI  - Understanding acute and chronic myeloid leukaemia.

PMID- 8539124
TI  - Direct action.

PMID- 8539125
TI  - Clearing the air.

PMID- 8539126
TI  - Careful recording.

PMID- 8539127
TI  - Roadside sanctuary.

PMID- 8539128
TI  - Playing politics.

PMID- 8539129
TI  - An integrated care approach.

PMID- 8539130
TI  - Easing the pressure.

PMID- 8539131
TI  - Changing the mattress.

PMID- 8539132
TI  - Management of burns.

PMID- 8539133
TI  - Fungating wounds.

PMID- 8539134
TI  - Dealing with difficult client behaviour.

PMID- 8539136
TI  - Health under fire.

PMID- 8539135
TI  - Trials of strength.

PMID- 8539137
TI  - D-grading debacle.

PMID- 8539138
TI  - Hungry fears.

PMID- 8539139
TI  - Men's health. Their own worst enemy.

PMID- 8539140
TI  - The life of Riley.

PMID- 8539141
TI  - Seclusion: the use of a stress model to appraise the problem.
AB  - This paper raises the issue of the use of seclusion in psychiatric practice by
      analysing the general theoretical underpinnings and the work of the RCN in this
      area. The literature suggests an impasse in understanding the thorny problem of
      the use of controlling measures in the management of the violent and aggressive
      individual. A new model of understanding is presented which deals with the issue
      of staff fear in relation to the decision to use seclusion which contributes
      towards both theory and practice development.

PMID- 8539142
TI  - Care management in the community: a case study.
AB  - The rhetoric surrounding the reforms of the NHS and Community Care Act makes much
      of the benefits to clients. The reforms have been promoted as a means of
      improving efficiency and making services more responsive to the needs of clients
      and carers. A case study is described here and the issues raised are considered.
      The incident occurred in 1994, the year following the implementation of the NHS
      and Community Care Act. It shows lack of coordination of services and teamwork, a
      poor response to identified needs and gaps in service provision.

PMID- 8539143
TI  - A study of the effectiveness of staff support groups.
AB  - This paper sets out to explore the value of attending a staff support group from
      the group members' perspective. Thirty four staff employed by King's Healthcare
      NHS Trust in South London were asked to complete a questionnaire which sought
      their views on two topics. First, their views on the advantages and disadvantages
      of attending a staff support group and second, their views on an outside
      facilitator for the groups. Group members came from community and school nursing
      backgrounds.

PMID- 8539144
TI  - The aggressive ward visitor: a critical incident analysis.
AB  - Since its conception by the aviation psychologist Flanagan the critical incident
      technique has been used in nursing studies to investigate many aspects of nursing
      practice. While its use as a nursing research tool and a classroom teaching aid
      have been discussed, little has been written on the use of the technique for
      individual reflection for those doing post-registration courses. In this paper,
      the author discusses her personal reflections following a critical incident and
      the need for the technique to be refined. The framework for reflection is taken
      primarily from Boyd and Fales. The model describes the process of creating and
      clarifying the meaning of an experience for oneself.

PMID- 8539145
TI  - Weight on their minds.

PMID- 8539146
TI  - Nutrition. Enteral feeding at home.

PMID- 8539148
TI  - Poor reception.

PMID- 8539147
TI  - The West end.

PMID- 8539149
TI  - Obstetric cholestasis.

PMID- 8539150
TI  - A positive contribution.

PMID- 8539151
TI  - Matching optimal pacemaker to patient: do we need a large scale clinical trial of
      pacemaker mode selection?

PMID- 8539152
TI  - Relationship between heart rate and oxygen kinetics during constant workload
      exercise.
AB  - BACKGROUND: Oxygen uptake during constant workload exercise increases
      exponentially from its resting value before reaching a steady state. The
      difference between the actual rate of oxygen consumption at the onset of exercise
      and the steady state is an oxygen deficit. Similarly, the normal sinus node
      increases its rate at the onset of exercise before achieving a steady state,
      thereby producing a heart rate deficit. The purpose of this study was to test the
      hypothesis that elimination of the heart rate deficit by an instantaneous
      increase in heart rate at the onset of constant workload exercise to the steady
      state level would reduce the oxygen deficit and improve the perceived difficulty
      of exertion as compared with the chronotropic response of the normal sinus node.
      METHODS AND RESULTS: Ten subjects with normal sinus node function who had DDD
      pacemakers implanted for AV block completed a symptom-limited maximal treadmill
      exercise test using the Chronotropic Assessment Exercise Protocol (CAEP) to
      assess sinus node function, maximal heart rate, and VO2max. The subjects then
      performed constant workload exercise tests (6-min duration) at a workload equal
      to approximately 50% of metabolic reserve with the pacemaker randomly programmed
      to each of three patterns of chronotropic response: (1) DDD (lower rate 60
      beats/min); (2) Fast (lower rate abruptly programmed to the expected value at 50%
      metabolic reserve); and (3) Overpaced (lower rate at least 80% of the age
      predicted maximum). The oxygen deficit was lower with the fast chronotropic
      response (434 +/- 238 mL O2) than with either the DDD (512 +/- 233; P = 0.02), or
      overpaced chronotropic patterns (488 +/- 238; P = 0.02 vs fast). The rate
      constant for change in VO2 was highest with the fast chronotropic pattern (2.85
      +/- 1.38) compared with either the DDD (2.25 +/- 0.64; P = 0.01) or overpaced
      (2.38 +/- 0.43; P = 0.02) patterns. The Borg perceived exertion rating was lowest
      with the fast chronotropic response (P = 0.02 vs DDD and P = 0.02 vs overpaced).
      CONCLUSIONS: The results of this study suggest that oxygen kinetics and
      exertional symptoms are improved by an abrupt increase in pacing rate at the
      onset of exercise to a value that is appropriate for metabolic demand as compared
      with the DDD pacing mode in patients with normal sinus node function. In
      contrast, an overly aggressive chronotropic response was not associated with
      improved oxygen kinetics or exertional symptoms.

PMID- 8539153
TI  - An approach in the assessment of pacing hemodynamics: a comparison of VVI and
      DDD.
AB  - Previous methods for assessment of pacemaker hemodynamics have been limited to a
      rigid hospital environment. An alternative is the ambulatory ventricular function
      monitor (C-VEST) that, with a single injection of technetium-99m, permits the
      continuous measurement of relative ejection fraction (EF) and cardiac output (CO)
      during the activities of daily living. A study of reproducibility and a
      comparison of dual chamber (DDD) and fixed rate ventricular (VVI) pacing are
      presented. Reproducibility was assessed in six patients (4 males; mean age 58,
      range 27-78 years) with a mean EF of 48.5% (range 34%-62%) and DDD pacemakers,
      implanted for conduction abnormalities. In addition, 11 patients (7 males; mean
      age 55.5, range 34-75 years) with a mean EF of 48.5% (range 34%-65%), chronic
      complete heart block, and DDD pacemakers were used for the comparative study.
      After an initial multigated scan, the monitor was positioned over the left
      ventricle and kept in place with the plastic C-VEST. The patients undergoing the
      reproducibility study performed three shuttle walking tests with 20 minutes of
      rest in between. The patients in the comparative study were randomized to either
      VVI or DDD mode and performed one shuttle walking test in each pacing mode. The
      results confirmed that the C-VEST produces reproducible results with no
      significant difference in peak CO between the three shuttle walks. In addition,
      it confirmed previous hemodynamic studies showing that DDD pacing was superior to
      VVI pacing both at rest (P < 0.004) and at exercise (P < 0.002). These findings
      show the C-VEST to be an extremely useful tool for the hemodynamic assessment of
      pacemaker patients.

PMID- 8539154
TI  - Low energy endocardial cardioversion of atrial arrhythmias in humans.
AB  - We assessed the feasibility of low energy endocardial defibrillation in patients
      with atrial fibrillation or atrial flutter who had failed a trial of
      pharmacological reversion with amiodarone. Low energy endocardial defibrillation
      under general anesthesia was attempted in 9 patients, 5 with atrial flutter and 4
      with atrial fibrillation (median duration of arrhythmia 3.75 months). Two large
      surface area endocardial leads were introduced percutaneously and sited in the
      right atrial appendage and at the right ventricular apex. A cutaneous patch
      electrode was placed on the left thorax. Biphasic shocks synchronized to the
      ventricular electrogram were used to terminate atrial arrhythmias. Three
      electrode configurations were evaluated in the following sequence at each energy
      level: atrial cathode to ventricular anode; ventricular cathode to atrial anode;
      atrial cathode to a combined ventricular and cutaneous anode. If endocardial
      defibrillation failed (0.5-10 J), transthoracic defibrillation using 200 joules
      followed by 360 joules, if required, was performed. Endocardial defibrillation
      was successful in all five patients with atrial flutter (0.5 J, 1.0 J, 1.0 J, 4.0
      J, and 10.0 J) but in only one patient with atrial fibrillation (10 J). On no
      occasion did successful defibrillation occur with one configuration when it had
      failed with an alternate configuration at that particular energy level.
      Ventricular fibrillation did not occur, and there were no other significant
      complications. Low energy endocardial defibrillation is feasible in patients with
      atrial flutter using large surface area electrodes. Although the success rate of
      atrial defibrillation was low, further work is required, particularly in patients
      with more recent onset of the arrhythmia and using a right to left electrode
      configuration.

PMID- 8539155
TI  - Analysis of the body surface ECG measured in independent leads during ventricular
      fibrillation in humans.
AB  - The degree of myocardial electrical organization during ventricular fibrillation
      remains unknown. The aim of this study was to compare the characteristics of the
      surface ECG on three independent and approximately orthogonal leads. Ten
      recordings of ventricular fibrillation, each induced at electrophysiology study
      and successfully terminated by direct current shock, were analyzed. Each
      recording was divided into 1-second epochs for analysis. Frequency analysis using
      the Fast Fourier Transform showed that the frequency of the dominant spectral
      peak increased significantly from a mean of 4.1 +/- 0.8 Hz to 5.2 +/- 0.7 Hz
      during the first 5 seconds of ventricular fibrillation. In 95% of the epochs
      analyzed, a similar dominant frequency was observed on either two or three ECG
      leads. Frequency agreement tended to increase as ventricular fibrillation
      evolved. This study shows that the rate of ventricular fibrillation increases
      rapidly during the first 5 seconds but only gradually thereafter, and that
      similar signal characteristics are observed on independent ECG leads. These
      findings are not compatible with the traditional view of incoherent myocardial
      activity during ventricular fibrillation.

PMID- 8539156
TI  - Comparison of sinus node response to exercise with responses from two different
      activity-based rate adaptive pacemakers in healthy subjects of different age
      groups.
AB  - The pacing rates from accelerometer-based (Excel) and piezoelectric-based
      (Legend) activity sensing rate adaptive pacemakers, both strapped externally in
      the pectoral position, were compared with sinus rate response in normal
      volunteers of two different age groups (group 1, mean age 35 +/- 16 years; group
      2, mean age 72 +/- 9 years) during various physical activities. Both pacemakers
      were programmed in manufacturers' nominal rate adaptive settings. Both types of
      activity sensing pacemakers programmed in this way showed chronotropic
      deficiencies to metabolic demand in healthy young subjects and in those matching
      the usual age of pacemaker implant, especially during "burst" activities. These
      data suggest that present recommended activity sensing rate response algorithms
      for accelerometer and piezoelectric pacemakers are inappropriate for many
      physical activities.

PMID- 8539157
TI  - Effects of initial polarity on defibrillation threshold with biphasic pulses.
AB  - BACKGROUND: Previous studies have shown that the polarity of epicardial patches
      significantly affects the defibrillation efficacy of monophasic shocks. However,
      whether this improvement can be extended to different pulsing methods and lead
      systems, such as biphasic shocks using endocardial defibrillating electrodes, is
      unknown. METHODS: Twenty consecutive patients undergoing testing and permanent
      implant using an Endotak lead system with a biphasic device were included in the
      study. In each patient the defibrillation threshold was determined delivering
      biphasic pulses with the distal coil as the cathode and the proximal coil as the
      anode during the positive phase and with the polarity reversed. The initial
      electrode polarity tested was chosen randomly. The defibrillation threshold was
      defined as the lowest pulse amplitude that effectively terminated ventricular
      fibrillation induced with 60-Hz alternating current. For each biphasic pulse peak
      voltage, pulse duration, resistance, and stored energy were recorded. RESULTS: Of
      the 20 patients, 12 (60%) had lower defibrillation threshold when the proximal
      coil was negative, whereas only 2 patients had a lower defibrillation threshold
      when the distal coil was negative. In four patients a subcutaneous patch would
      have been required if only the biphasic pulse with the distal coil as negative
      had been tested. The mean stored defibrillation threshold energy was lower with
      the configuration using the proximal coil as cathode (16.3 +/- 8.8 J vs 21.5 +/-
      11 J; P < 0.01). CONCLUSION: Change in the initial polarity of biphasic shocks
      may influence defibrillation efficacy and should, therefore, be assessed in each
      patient to achieve a more satisfactory safety margin and minimize the use of more
      invasive lead configurations.

PMID- 8539158
TI  - A technique for stable His-bundle recording and pacing: electrophysiological and
      hemodynamic correlates.
AB  - His-bundle electrograms recorded from intracardiac electrode catheters have been
      a mainstay of basic and clinical electrophysiology. However, consistent His
      bundle pacing has not been as readily achieved. In 13 dogs anesthetized with
      sodium pentobarbital (30 mg/kg), we recorded leads II and aVR as well as the His
      bundle electrogram from the aortic root. A deflectable tip multipolar catheter (4
      rings, 5 mm apart) was introduced via the right jugular vein into the right
      ventricle (RV). In 7 dogs, using fluoroscopy, the tip was placed under the
      tricuspid septal leaflet. In the other 6, after thoracotomy, the same placement
      was made by palpation through the right atrial wall. Stable His-bundle and right
      bundle (Rb) branch recordings were made from distal and proximal electrode pairs,
      respectively. H-V intervals measured 35 +/- 6 ms from the aortic root and 33 +/-
      5 ms from under the tricuspid leaflet (P = NS). Rb-V measured 25 +/- 4 ms.
      Consistent His-bundle pacing was accomplished from the aortic root with an
      average stimulus intensity of 6 +/- 10 mA and from the tricuspid leaflet at 16 +/
      8 mA (P < 0.05). In 7 anesthetized dogs we compared the hemodynamic effects of A
      V sequential pacing at the same heart rates using the His-bundle recording site
      under the septal leaflet of the tricuspid valve (A-H pacing) or pacing from the
      RV apex (A-RV pacing). Under normal conditions there was a significant depression
      of mean blood pressure when A-RV pacing was compared with atrial pacing (AOO);
      but no difference was found between AOO and A-H pacing.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8539159
TI  - Carotid sinus syndrome: acute hemodynamic evaluation of a dual chamber pacing
      mode.
AB  - Cardiac pacing is the treatment of choice in patients with carotid sinus syndrome
      (CSS). Three different pacing modes were tested in 20 patients (16 males, 4
      females; mean age 75 +/- 9 years) with documented symptomatic CSS. Three carotid
      sinus massages (CSM) were performed in each supine patient successively paced in
      random order in: DDI--the reference pacing mode; DDD--automatic mode conversion
      (DDD/AMC) allowing automatic switching from AAI to DDD when AV block occurs;
      DDD/AMC plus atrial acceleration (DDD/AMC+acc); and OOO (CSM without pacing) to
      determine whether the vasodepressive effect was still present 10 minutes after
      the preceding CSM. Intraarterial blood pressure was continuously monitored.
      Results were expressed as the value of the mean systolic BP at T0 + 3 s + 6 s ...
      T0 + 30 s divided by the value of the mean systolic blood pressure prior to onset
      of CSM. The drop in arterial blood pressure was more severe in the DDI mode than
      in DDD/AMC (P < 0.001) and DDD/AMC+acc (P < 0.0001) in 20 patients. In the OOO
      mode, the drop in arterial blood pressure was most marked and greater than in the
      DDI mode (P < 0.0001). The average time between start of the CSM and onset of the
      drop in blood pressure was the same in the three dual chamber modes. We conclude
      that the DDD/AMC mode significantly improves the vasodepressor response to CSM
      compared to the DDI mode. There is a current trend favoring DDD/AMC+acc over
      DDD/AMC.

PMID- 8539160
TI  - Dynamic relationship between the Q-aT interval and heart rate in patients with
      long QT syndrome during 24-hour Holter ECG monitoring.
AB  - The purpose of this study was to investigate the dynamic relationship between
      heart rate and the Q-aT interval (the interval from the Q wave to the T wave
      apex) in patients with long QT syndrome. The QT to heart rate relation is useful
      for evaluating abnormalities of the ventricular repolarization, but its clinical
      application to the long QT syndrome requires accurate computer aided measurement
      of the QT interval and the sampling of a large number of beats. Therefore, the Q
      aT interval was used on the basis of some reports that the heart rate dependency
      of the QT interval was concentrated in the Q-aT interval. Recent advances in the
      computer technology have allowed analysis of the relationship between the Q-aT
      and RR intervals on Holter ECG recordings. However, in addition to a prolonged QT
      interval, most patients with long QT syndrome have bizarre and variable T waves
      and the influence of this T wave morphology on the Q-aT to heart rate relation
      has not been clarified. We investigated the dynamic relationship between the Q-aT
      interval and heart rate in 10 patients with long QT syndrome and 11 control
      subjects using our original computer algorithm for the analysis of 24-hour Holter
      ECG recordings. The patients showed morphological T wave changes associated with
      heart rate changes during Holter recordings and these affected the Q-aT interval.
      The patients showed the following characteristics in the relationship between the
      major T wave peak and the RR interval: (1) a modestly decreased correlation
      between Q-aT and RR than in the control subjects (a median r value of 0.87 vs
      0.93; P = 0.001); and (2) a steeper Q-aT/RR slope than in controls (a median
      slope of 0.24 vs 0.16; P < 0.05). Abnormal and variable T wave morphology in the
      long QT patients was closely related to a modestly decreased correlation between
      Q-aT and RR than in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539161
TI  - Resetting and transient entrainment of ventricular tachycardia.

PMID- 8539162
TI  - Conversion of analog signals into computer oriented data.

PMID- 8539163
TI  - Improving cost, access, and quality: why did they fail and how do we succeed?

PMID- 8539164
TI  - Third successful pregnancy and delivery in a patient with permanent junctional
      reciprocating tachycardia.

PMID- 8539165
TI  - Emergent radiofrequency ablation of the AV node in a neonate with unstable,
      refractory supraventricular tachycardia.
AB  - Supraventricular tachycardia due to accessory atrioventricular connections in
      infants is usually well-tolerated. Rarely an infant can have supraventricular
      tachycardia that is incessant and refractory to medical therapy. We describe a
      patient with supraventricular tachycardia detected prenatally that caused severe
      cardiac dysfunction and hemodynamic instability after birth.

PMID- 8539166
TI  - Pacemaker inhibition and asystole in a pacemaker dependent patient.
AB  - A 17-year-old female with Kearns Sayre syndrome, complete heart block, and an
      implanted single chamber (VVIR) pacemaker, underwent testing with a GSM cellular
      phone that was placed directly over the pacemaker site. The pacemaker was
      immediately inhibited when the phone began to operate. A 6.5-second period of
      complete heart block with asystole occurred until the phone was switched off.

PMID- 8539167
TI  - Catheter aided repositioning of a displaced permanent pacemaker lead.
AB  - A 91-year-old woman, who had a pacemaker implanted in 1977, underwent replacement
      of a pulse generator and lead in 1995 because of recurrent syncope. The new lead
      dislodged the next day and migrated to the pulmonary artery. Because of her
      dependence on continued pacing, repeated resuscitation was required. Considering
      her advanced age and the impact of cardiopulmonary resuscitation on her general
      condition, we attempted catheter aided repositioning of the pacemaker lead. The
      procedure was technically successful; lead position was stable and optimal pacing
      parameters were attained. She was discharged in good condition.

PMID- 8539168
TI  - Migration of a fractured retention wire in the pulmonary artery from an active
      fixation atrial lead.
AB  - A fragment of fractured retention wire of an atrial J lead (Accufix) was found in
      the pulmonary artery in an asymptomatic patient by routine chest X ray,
      fluoroscopy, and pulmonary angiography. The lead itself looked normal in these
      imaging studies. Results after successful surgical removal was reported.

PMID- 8539169
TI  - Spurious programming.

PMID- 8539170
TI  - Transvenous defibrillator lead damage.

PMID- 8539171
TI  - Transtelephonic monitoring.

PMID- 8539172
TI  - STIMAREC report.

PMID- 8539173
TI  - Smoke screen.

PMID- 8539174
TI  - Bereavement cards successful for oncology unit.

PMID- 8539175
TI  - Patient literacy and the readability of written cancer educational materials.
AB  - PURPOSE/OBJECTIVES: The purpose of this study was to determine whether the
      reading level of educational materials for patients with cancer corresponds to
      the reading abilities of a sample of patients. A secondary aim was to describe
      what type of educational materials patients with cancer report as most helpful.
      DESIGN: Descriptive, cross-sectional. SETTING: Outpatient oncology clinics at an
      urban Veterans Affairs Medical Center. SAMPLE: A convenience sample of 63
      outpatients with cancer. METHODS: Investigators used the Word Recognition
      Achievement Test-Revised Level (WRAT-R2) to measure patients' reading levels.
      They used the Flesch Index to analyze the reading levels of the booklets that the
      patients used (14 booklets developed by the American Cancer Society and 16
      developed by the National Cancer Institute). Data were analyzed through
      descriptive statistics and a Wilcoxon signed rank test. MAIN RESEARCH VARIABLES:
      Patient and booklet reading levels. FINDINGS: The reading level of 27% of the
      sample was less than that of all 30 pamphlets (less than a sixth-grade reading
      level). Seventeen percent of the patients had a reading level between sixth and
      eighth grades (representing 47% of the pamphlets). Twenty-nine percent of the
      sample had WRAT scores between 9th and 12th grades (representing 80% of the
      pamphlets). Only 27% had WRAT scores of the 13th grade and above. Twenty-six
      percent of the patients preferred written educational materials alone, while 57%
      of patients desired more than one method of instruction. CONCLUSION: Written
      materials for the education of patients with cancer must be carefully matched to
      patient reading levels. Written materials may not be the only desirable mode of
      instruction. IMPLICATIONS FOR NURSING PRACTICE: Given the increasing complexity
      of cancer care, shorter hospital stays, and a shift toward busy ambulatory care
      centers, nurses need to develop creative, innovative, and comprehensive patient
      education programs that are understandable to patients and that use multiple
      types of instruction.

PMID- 8539176
TI  - Cancer fatalism among elderly Caucasians and African Americans.
AB  - PURPOSE: To determine the relationship between selected demographic factors
      (e.g., education, income, ethnicity, gender, age) and cancer fatalism. DESIGN:
      Descriptive study. SETTING: Randomly selected senior citizen centers in a
      southern state. SAMPLE: The majority of the participants (N = 192) were female
      African Americans. Mean age of participants was 76 years, mean years of education
      was < or = 8 years, and mean income was below $6,500 per year. METHODS:
      Demographic data was collected and Powe Fatalism Inventory was completed in face
      to-face interviews. MAIN RESEARCH VARIABLES: Education, income, ethnicity,
      gender, age, and cancer fatalism. FINDINGS: Significant negative correlations
      between cancer fatalism and education and income were found. Significant
      correlations also existed between cancer fatalism and ethnicity and gender. Age
      was not a significant predictor of cancer fatalism. CONCLUSIONS: As participants'
      level of education and income decreased, cancer fatalism scores increased.
      African Americans and females had higher mean cancer fatalism scores. Education,
      income, ethnicity, and gender could be used to predict cancer fatalism scores.
      IMPLICATIONS FOR NURSING PRACTICE: Future research should evaluate the
      relationship between cancer fatalism and early detection practices.

PMID- 8539177
TI  - Leukemia during pregnancy.
AB  - PURPOSE/OBJECTIVE: To review the literature on pregnancy and leukemia and present
      a case report that describes the effects of cancer treatment on a developing
      fetus. DATA SOURCES: Published articles, book chapters, personal observation.
      DATA SYNTHESIS: A diagnosis of acute myelogenous leukemia requires urgent
      initiation of intensive treatment. During pregnancy, chemotherapy treatment is
      determined by gestational development and the woman's general health status.
      CONCLUSIONS: Babies born to leukemic mothers treated after the first trimester
      rarely are affected by the disease. Meticulous medical and nursing management is
      critical to ensure that treatment and side effects do not adversely affect the
      baby or the patient. IMPLICATIONS FOR NURSING PRACTICE: Goals of care are to
      prevent bleeding, infection, injury, and premature delivery; to assist the
      patient and family in coping with a new diagnosis, alteration in role
      performance, and body image changes; and to maintain adequate nutritional status.

PMID- 8539178
TI  - The effects of psychoeducational care provided to adults with cancer: meta
      analysis of 116 studies.
AB  - PURPOSE/OBJECTIVES: To determine how educational and psychosocial care provided
      to adults with cancer affects seven outcomes--anxiety, depression, mood, nausea,
      vomiting, pain, and knowledge. DESIGN: Meta-analysis. SAMPLE: 116 intervention
      studies. A standardized mean difference between a treatment and control group
      (i.e., an effect-size value) was calculated for 98 studies; for 18 additional
      studies, it was only possible to code the direction of treatment effect (i.e.,
      whether the treatment or control group had a higher score). Most analyses were
      limited to the 98 studies from which an effect-size value was obtainable. These
      studies were published between 1976 and 1993 and were based on data obtained from
      5,326 patients with cancer. METHODS: A comprehensive literature search yielded
      more than 20,000 potentially relevant citations that were reviewed. Study,
      subject, treatment, and outcome characteristics of the studies meeting selection
      criteria were coded. MAIN RESEARCH VARIABLES: Manner of subject assignment to
      treatment condition; type of control group; publication form; type of
      psychoeducational care; and the outcomes of anxiety, depression, mood, nausea,
      vomiting, pain, and knowledge. FINDINGS: Statistically significant, beneficial
      effects were found in relation to all seven of the outcomes. Three threats to
      validity were examined and were not found to be a problem related to the outcomes
      examined. CONCLUSIONS: Psychoeducational care was found to benefit adults with
      cancer in relation to anxiety, depression, mood, nausea, vomiting, pain, and
      knowledge. Differentiating among the effectiveness of various types of
      psychoeducational care was problematic. To maximize the utility of this knowledge
      for clinicians, more research is needed to evaluate the relative effectiveness of
      different types of psychoeducational care. IMPLICATIONS FOR NURSING PRACTICE: A
      strong research base has established the beneficial effects of psychoeducational
      care. Clinicians should examine their practice to determine if research-based
      psychoeducational care is being used sufficiently.

PMID- 8539179
TI  - Reaching out to the African American community through innovative strategies.
AB  - PURPOSE/OBJECTIVES: To describe the University of Pittsburgh Cancer Institute's
      African American Cancer Program, including innovative strategies that were used,
      barriers that were encountered, an evaluation of each component, and future
      directions and implications. DATA SOURCES: Published articles, references from
      bibliographies, census data, personal contact, unpublished data. DATA SYNTHESIS:
      Cancer morbidity and mortality is higher among African Americans than Caucasians.
      The University of Pittsburgh Cancer Institute pilot-tested four interventions to
      increase awareness, provide education and early detection opportunities, and
      overcome barriers to cancer care among African Americans. CONCLUSION: Constant
      presence, cultural sensitivity, and repetition are necessary to overcome the
      barriers to increased awareness and behavioral changes in the African American
      community. A more formalized evaluation component is necessary to draw definitive
      conclusions. IMPLICATIONS FOR NURSING PRACTICE: To develop cancer prevention and
      education programs that meet the unique needs of African Americans, nurses must
      be aware of barriers and cultural differences.

PMID- 8539180
TI  - The role of cladribine in the treatment of lymphoid malignancies.
AB  - PURPOSE/OBJECTIVES: To review clinical applications and nursing care activities
      for patients receiving cladribine, a synthetic antineoplastic agent used to treat
      lymphoid malignancies. DATA SOURCES: Clinical trial data, published articles,
      reports from oncology nurses, and personal observations. DATA SYNTHESIS:
      Cladribine has shown response rates of nearly 90% in patients with hairy cell
      leukemia after a single, seven-day continuous infusion. Toxicities generally are
      mild, predictable, and rapidly reversible after therapy is discontinued.
      CONCLUSIONS: Currently, cladribine primarily is used in hairy cell leukemia
      therapy. Clinical trials of cladribine in treating other hematologic
      malignancies, primarily chronic lymphocytic leukemia and non-Hodgkin's lymphoma,
      have demonstrated encouraging results. IMPLICATIONS FOR NURSING PRACTICE: Nursing
      care for patients who receive cladribine involves management of side effects,
      which commonly include myelosuppression and fever, and monitoring of hemoglobin,
      platelet levels, and body temperature. Fever develops in most patients receiving
      cladribine but is usually transient and easily treated with acetaminophen.
      Infection as a cause of fever must be ruled out, especially in patients with
      neutropenia.

PMID- 8539181
TI  - Information and decision-making preferences of men with prostate cancer.
AB  - PURPOSE/OBJECTIVES: To determine whether a relationship exists between
      preferences for involvement in decision making and type of information in
      patients with cancer. DESIGN: Survey, correlational. SETTING: Community urology
      clinic in Winnipeg, Manitoba, Canada. SAMPLE: Convenience sample of 57 men (mean
      age of 71 years). METHODS: Subjects completed a card sort to elicit their
      preferred role in treatment decision making. A two-part questionnaire measured
      the type and amount of information preferred. FINDINGS: The majority (57.9%) of
      men preferred a passive decision-making role. Information on disease advancement,
      likelihood of cure, and types of treatment available were the three preferred
      categories of information. Men in the collaborative group and those who wanted
      their physician to make treatment decisions-only after seriously considering
      their opinions-also wanted significantly more information in these three
      categories. Married men ranked self-care information as significantly less
      important than did single men. Information preferences were similar regardless of
      preferred decision-making role. CONCLUSIONS: Although the majority of men in this
      sample wanted their physician to make final treatment decisions, they did want to
      be informed. Information preferences were similar to other groups of patients
      with cancer. Future clinical studies are required to determine if providing these
      men with more information will enable them to assume a more active decision
      making role. IMPLICATIONS FOR NURSING PRACTICE: Given the small variance in
      decision-making and information preferences accounted for by sociodemographic and
      treatment/disease-related factors, individual assessment of these preferences
      remains the best clinical approach.

PMID- 8539183
TI  - Cancer resources in the United States.

PMID- 8539184
TI  - Developing pain management education using guidelines.

PMID- 8539182
TI  - Using brochures to educate the public about the early detection of prostate and
      colorectal cancer.
AB  - PURPOSE: To describe the development and the evaluation of two brochures intended
      to educate the public about prostate and colorectal cancer screening. DATA
      SOURCES: Clinical experience and published books, articles, and brochures. DATA
      SYNTHESIS: Personnel at the Cancer Screening Center of the Deaconess Health
      System in St. Louis, MO, developed two brochures intended to educate the public
      about prostate cancer and colorectal cancer screening. These brochures focus on
      early detection (based on American Cancer Society guidelines), signs and
      symptoms, and risk factors related to prostate and colorectal cancer.
      CONCLUSIONS: These brochures can be used effectively to educate a large number of
      people about prostate and colorectal cancer. IMPLICATIONS FOR NURSES: Oncology
      nurses may find these brochures to be an effective adjunct to existing resources
      used to educate the public about early detection of prostate and colorectal
      cancer.

PMID- 8539185
TI  - Using guidelines for education, policy making, and assessing quality of care.

PMID- 8539186
TI  - Putting guidelines to work in an ambulatory care setting.

PMID- 8539187
TI  - Implementing guidelines on acute pain management.

PMID- 8539188
TI  - Standard of care for pain management interventions.

PMID- 8539189
TI  - Guidelines supplement comprehensive staff education program.

PMID- 8539190
TI  - Therapeutic uses of intravenous immunoglobulin (IVIG) in children.

PMID- 8539191
TI  - Cerebral palsy.

PMID- 8539192
TI  - Management of fatal illness and death in children or their parents.
AB  - Assisting families facing a death necessitates constant reevaluation of each
      family's adaptation to the illness. Protracted terminal illness is particularly
      difficult because the prolonged stress, suffering, and pain may be much more
      difficult to cope with than the death itself. Successful management requires
      acknowledging the families' emotions, assuring them that their responses are
      normal, and providing them a balanced perspective through supportive, honest, and
      open communication. In so doing, the pediatrician can help families predict
      reactions, manage problems, and avoid long-term psychological consequences.

PMID- 8539193
TI  - Degenerative central nervous system disease.

PMID- 8539195
TI  - Index of suspicion. Case 2. Wiedemann-Beckwith syndrome.

PMID- 8539194
TI  - Index of suspicion. Case 1. Toxocara canis and Ascaris infection with lead
      poisoning.

PMID- 8539196
TI  - Index of suspicion. Case 3. Strangulated hernia of the small intestine.

PMID- 8539197
TI  - Community-acquired pneumonia. Cost-effective antimicrobial therapy.
AB  - At present, three antibiotics (doxycycline, ofloxacin [Floxin], and azithromycin
      [Zithromax]) provide optimal therapy for both typical and atypical community
      acquired pneumonias. These agents permit a monotherapeutic approach and are also
      ideal for intravenous-to-oral switch therapy, which results in great cost savings
      for an institution and an earlier discharge for the patient. The era of oral
      therapy has been ushered in because of economic imperatives. Fortunately,
      bioavailability of these three antibiotics is essentially the same when
      administered intravenously or orally. Moderately to severely ill patients may be
      safely and effectively treated via the oral route alone; however, most patients
      who require admission to the hospital are initially given intravenous therapy,
      after which a change is made to an oral antibiotic equivalent as soon as
      possible.

PMID- 8539198
TI  - Atypical pneumonia. Extrapulmonary clues guide the way to diagnosis.
AB  - In atypical pneumonia, causative organisms are difficult to isolate, so careful
      clinical assessment is essential in arriving at a working diagnosis. Definitive
      diagnosis through serologic testing is usually retrospective. Either a high
      initial titer or a fourfold or greater rise between the acute and convalescent
      titer is considered diagnostic in a patient with compatible illness. Legionella
      and mycoplasma organisms may be cultured from respiratory secretions if plated on
      appropriate culture media. Using a syndromic approach, physicians can almost
      always differentiate typical from atypical community-acquired pneumonia and
      narrow diagnostic possibilities among the atypical pathogens, making possible
      institution of early, possibly lifesaving, empirical therapy.

PMID- 8539199
TI  - Radiographic mimics of pneumonia. Pulmonary disorders to consider in differential
      diagnosis.
AB  - Pinpointing the source of roentgenographic lung abnormalities can be challenging
      because many noninfectious pulmonary disorders mimic pneumonia. The authors of
      this article discuss the most common radiographic presentations of lung disorders
      that may be mistaken for pneumonia, including focal and diffuse infiltrates,
      nodules, cavities, and pleural effusion. They also outline the role of thorough
      history taking and examination in prompt and accurate diagnosis of pulmonary
      disorders.

PMID- 8539200
TI  - The cost of caring: who heals the healer?

PMID- 8539201
TI  - Delayed resolution of pneumonia. When is slow healing too slow?
AB  - Slowly resolving or nonresolving pneumonia is a clinical challenge, but we
      believe it can be dealt with in a rational and decisive manner. The following
      risk factors have been established for delayed radiographic resolution of
      pneumonia and should be considered in patient evaluation: Coexisting medical
      conditions History of smoking, Advanced age, Multilobar involvement, Persistent
      fever or leukocytosis. Diabetes, chronic obstructive pulmonary disease, renal
      failure, and alcohol abuse can impair immune function, which slows normal
      clearing of infiltrates. Common and uncommon infectious agents, conditions that
      mimic pneumonia (eg, a neoplasm, congestive heart failure), and pulmonary
      complications (eg, abscess) can also result in delayed resolution.

PMID- 8539202
TI  - Anorexia nervosa and bulimia nervosa. When the pursuit of bodily 'perfection'
      becomes a killer.
AB  - Eating disorders probably result from a combination of emotional, physical, and
      sociologic factors and are encouraged by a society that values appearance as a
      measure of worth. Once believed to be a problem largely among young women, the
      disorders are being found increasingly among children, young athletes, men, and
      elderly women. Often accompanied by depression, anxiety, and personality
      disorders, eating disorders may be difficult to diagnose. Patients with anorexia
      nervosa often deny that they have a problem, despite obvious physical signs.
      Patients with bulimia nervosa may hide their binging and purging and have no
      overt signs. Primary care physicians may be the first to suspect potential
      problems, including a patient's fixation on food, weight, dieting, physique, and
      exercise. Sometimes, patients who have struggled in silence for years turn to
      their trusted physician for support and understanding. The first step in
      treatment is to address the medical complications caused by the unhealthy eating
      habits. Once nutritional health has been restored, patients need to reverse their
      entrenched and distorted body-image ideas through psychotherapy.

PMID- 8539203
TI  - Treating pruritus. What's new in safe relief of symptoms?
AB  - In several cutaneous disorders, pruritus is both the primary symptom and the
      cause of perpetuating factor. Therefore, one focus of therapy should be on
      treating pruritus and thereby preventing or aiding in the resolution of skin
      lesions. Several treatment options are available, including nonpharmacologic
      methods; use of emollients, tar preparations, and other topical agents;
      ultraviolet B therapy; and use of oral antihistamines or corticosteroids. A new
      topical tricyclic agent is now available that adds a promising therapeutic
      approach.

PMID- 8539204
TI  - Hypertensive crises. The need for urgent management.
AB  - Although hypertensive crises are now relatively uncommon, they often are life
      threatening when they do occur and demand early recognition and management to
      minimize morbidity and mortality. Most patients have essential hypertension, and
      withdrawal from an antihypertensive drug is the most common cause of acute
      elevation of blood pressure. Short-acting parenteral agents are generally
      recommended for management of hypertensive crises. In most patients with
      hypertensive emergencies, the mean arterial pressure is lowered 25% over 2 to 4
      hours. Both cerebral and coronary hypoperfusion must be avoided.

PMID- 8539205
TI  - Two by two.

PMID- 8539206
TI  - Your 'window' to the world's information.

PMID- 8539207
TI  - Defining the referral process.

PMID- 8539208
TI  - NSAIDs and anticoagulant therapy.

PMID- 8539209
TI  - Treatment of giardiasis.

PMID- 8539210
TI  - Moderate Parkinson's disease. Strategies for maximizing treatment.
AB  - Motor fluctuations and dyskinesia often develop in patients with Parkinson's
      disease after 3 to 5 years of levodopa therapy. Dosage adjustments, addition of a
      second medication to the drug regimen, and dietary modifications may help
      maximize response to symptomatic therapy. Given the dramatic variability of
      symptoms and response to treatment, drug regimens must be individualized
      according to the patient's needs. In newly diagnosed cases of Parkinson's
      disease, administration of selegiline hydrochloride (Eldepryl) may slow symptom
      development and delay the need for levodopa therapy. Many physicians prescribe
      selegiline initially for its symptomatic and potential neuroprotective benefits.

PMID- 8539211
TI  - Accidental hypothermia. When thermoregulation is overwhelmed.
AB  - The diagnosis of hypothermia must be entertained when patients present with
      unexplained mental status changes or arrhythmias. Prompt recognition and
      aggressive treatment of complications should reduce cold-related fatalities. The
      choice of an appropriate rewarming method must be individualized and depends on
      the severity of hypothermia and the patient's degree of hemodynamic tolerance.

PMID- 8539212
TI  - Community-acquired pneumonia. What's needed for accurate diagnosis.
AB  - Characteristic clinical findings of fever, cough, and rhonchi, together with a
      new infiltrate on chest films and documentation of a pathogen, establish a
      diagnosis of infectious pneumonia. Several factors have had an impact on the
      approach to diagnosis of community-acquired pneumonia by the primary care
      physician. These include the expanding number of possible pathogens as well as
      their increasing resistance to antimicrobial therapy. Although the clinical
      presentation may suggest a specific cause, findings often overlap too much for
      reliable identification of the specific agent on clinical grounds alone.
      Isolation of the microorganism or determination of the presence of a specific
      antigen or antibody is necessary. However, even after extensive studies are
      performed, the pathogen remains unidentified in 30% to 50% of cases. The primary
      care physician therefore needs to balance reasonable use of diagnostic tests with
      empirical therapy.

PMID- 8539213
TI  - [Small thyroid nodules and microcancers].
AB  - Thyroid nodules less than one centimetre in diameter raise the problem of
      differential diagnosis between a benign formation and cancer. The question is of
      major importance since nodules can be found in approximately one-half of the
      population. Fine-Needle Aspiration should be performed if the nodule is palpable.
      When cytologic diagnosis is not possible, the discovery of a small nodule in the
      thyroid gland is not an alarming finding in itself as long as the absence of
      involvement of the satellite nodes or other associated symptomatology is
      confirmed. We have operated 102 patients with differentiated microcancers with no
      metastasis other than local node involvement. All have been seen regularly for
      annual check-ups and only 2 have developed pulmonary and bone metastases with a
      fatal outcome. The prognosis of microcancers is thus much better than that of
      larger tumours since in a series of more than 500 cancers we have observed 5 and
      10 year survivals of 96 and 92% respectively. In addition, unlike large tumours,
      small cancers of the thyroid are not anaplastic. We thus propose annual
      surveillance for patients with uncomplicated small nodules of the thyroid gland
      less than 2 cm in diameter. Complementary examinations should be limited.
      Conversely we operate the nodules exceeding 2 cm in order to reduce the frequency
      and severity of thyroid cancer. It should be recalled that neither clinical
      manifestations, echography, thyroglobulin, needle biopsy, nor any other
      diagnostic tool has been shown to have sufficient prognostic power to predict the
      benign nature of a voluminous nodule.

PMID- 8539214
TI  - [Destructive arthritis of the hip in Crohn disease. 10 cases].
AB  - OBJECTIVES: Destructive arthritis of the hip joint is a rare manifestation of
      Crohn's disease. We evaluated its frequency and clinical features in comparison
      with spondylarthritis and assessed the clinical course. METHODS: One hundred
      patients with Crohn's disease were followed prospectively in search of
      destructive arthritis of the hip joint. Patients with both Crohn's disease and
      manifestations of inflammatory joint disease hospitalized in three rheumatology
      units were also evaluated retrospectively. RESULTS: The prevalence of destructive
      hip disease was 2% in patients with Crohn's disease. Ten patients had destructive
      arthritis of the hip. Three had ankylosing spondylitis, 5 had spondylarthritis
      not responding to the criteria of ankylosing spondylitis and 2 had no axial joint
      disease. In all patients, signs of hip joint disease were a narrowed intra
      articular space, bone condensation, osteophytosis and features of joint
      destruction. Manifestations were similar to those in patients with hip joint
      disease related to idiopathic ankylosing spondylarthritis. The clinical course
      was poorly controlled by anti-inflammatory drugs or treatment of the inflammatory
      bowel disease. Synoviorthesis were required and were effective in most cases.
      Total hip replacement was required in 3 cases. CONCLUSION: Destructive arthritis
      of the hip in patients with Crohn's disease is a rare complication causing severe
      functional impairment further handicapping the patient with a chronic bowel
      disease.

PMID- 8539215
TI  - [Evaluation of the lithogenic risk in renal lithiasis. Value of urine density
      measurement].
AB  - OBJECTIVE: Measuring specific gravity of urine is a simple means of self
      monitoring for urolithiasis patients. METHODS: We evaluated the reliability of
      two test strips (N-Multistix and Combur-Stix) and determined the relationship
      between urine specific gravity and crystal formation in first morning urine in
      179 patients with calcium oxalate lithiasis. Urine hydrometry was used as the
      reference method. RESULTS: There was a good correlation between urine density
      read on the test strips and hydrometry (r = 0.733 for N-Multistix and 0.697 for
      Combur-Stix). Hydrometry showed little pH effect but the test strips gave results
      correlated with urine pH (r = 0.764 and 0.813 respectively). When urine pH was
      below 6.5, the specific gravity of the urine was overestimated; inversely for pH
      > 7, it was underestimated. Correction factors were obtained by comparing test
      strip values with specific gravity measurements for pH level between 4.5 and 8.
      There were crystals in 66% of the urine samples with a density > or = 1012 g/l.
      In contrast, 75% of the samples below this value were crystal free. There was a
      close relationship between 24-hour urine volume and specific gravity (n = 124; r
      = 0.778): a specific gravity of 1.012 corresponded to 2100 ml urine output. For
      24% of the patients, specific gravity of the morning urine was > or = 1.012
      despite a 24-h urine output > or = 2100 ml, indicating insufficient urine
      dilution during the night. CONCLUSION: Measurement of specific gravity with test
      strips with correction for pH can be a simple way to measure the specific gravity
      of urine and assess whether urine dilution is sufficient to reduce the risk of
      crystal formation, the main risk factor in urolithiasis patients.

PMID- 8539216
TI  - [Long-term results of total conservative parotidectomy for pleomorphic adenoma].
AB  - OBJECTIVES: Evaluation of the long-term results (10 and 15 years) achieved with
      total conservative parotidectomy for pleomorphic adenoma. METHODS: A
      retrospective analysis of the files of 127 patients with pleomorphic adenoma of
      the parotid gland consecutively treated with a total conservative parotidectomy
      at our department from 1970 to 1985. Actuarial analysis (Kaplan Meier method) of
      survival and local recurrence, as well as overall estimation of immediate and
      definite postoperative facial paresis and paralysis was performed. RESULTS: Ten-
      and fifteen-year survival and local control estimations were 90.8% and 99.1%,
      respectively. Immediate and permanent facial paresis and paralysis overall
      estimates were 64.6% and 6.3% and 2.1% and 0%, respectively. CONCLUSION: Total
      conservative parotidectomy for pleomorphic adenoma results in a very high long
      term local control associated with a very low rate of facial dysfunction.

PMID- 8539217
TI  - [Pneumococcal septic arthritis in HIV infection].
AB  - Infections due to pneumococci are frequent in patients infected with the human
      immunodeficiency virus (HIV), but joint infections are rare. We observed two
      cases of septic arthritis due to pneumococci in two non-haemophilic HIV
      seropositive patients. In the first case, a 31-year old drug addict who had
      undergone splenectomy, developed hip joint infection during an episode of
      meningitis due to pneumococci. The germ was moderately sensitive to ampicillin.
      The second case involved the knee joint in a 29-year-old woman who developed
      pneumococcal pneumonia after a trip to Zaire. In both cases, joint infection
      developed after antibiotics had been initiated, and in the first case, after the
      infection appear to be under control. This would be similar to "post-infectious"
      arthritis described in gonococcal and meningococcal infections. In HIV positive
      patients, joint infections are rare compared with other types of
      immunodepression, but can be observed in all stages of the disease. A total of 75
      cases have been reported in the literature, including 8 cases due to pneumococci.
      These joint infections could be another argument in favour of anti-pneumococcal
      vaccination in HIV positive patients.

PMID- 8539218
TI  - [Treatment of primary hyperhidrosis of the upper limbs by transthoracic
      endoscopic sympathectomy].
AB  - Primary hyperhidrosis of the upper limbs has an important impact on the subject's
      social and psycho-affective equilibrium. These patients have two main problems.
      First physicians are not sufficiently aware of the therapeutic possibilities and
      secondly the generally poor reputation of surgery in this indication.
      Transthoracic endoscopic sympathectomy has completely changed the treatment of
      hyperhidrosis of the upper limbs. It is now considered to be the reference
      treatment in severe cases. The surgical procedure is simple and allows
      simultaneous treatment of both sides. There is no mortality and morbidity is
      extremely low quantitatively and of little consequence qualitatively. The
      therapeutic protocol is short and immediate and long-term results are excellent
      in 98 to 100% of the patients.

PMID- 8539219
TI  - [Pulmonary arterial hypertension: medical treatment and surgical indications].
AB  - Pulmonary hypertension is characterized by a poor prognosis which, therefore,
      justifies its treatment. Pulmonary vascular endothelium plays a pivotal role in
      the underlying mechanisms of different forms of pulmonary hypertension. Various
      paracrine factors, including nitric oxide, prostacyclin and endothelium-1, are
      synthesized by the endothelium. Nitric oxide and prostacyclin are powerful
      vasodilators, which also inhibit vascular smooth muscle proliferation and
      platelet aggregation. Endothelium-1 is probably one of the most potent
      vasoconstrictor known to date. The net effect of endothelial dysfunction results
      in increased vasoconstriction, platelet aggregation and occurrence of thrombosis,
      whereas vasodilatation is impeded. In primary pulmonary hypertension, acute
      pulmonary vasodilatation is currently sought using inhaled nitric oxide, oral
      calcium channel blockers or infused prostacyclin to predict the long-term effects
      of pulmonary vasodilators which might improve the quality of life and survival in
      some patients. Similar result could be obtained with anticoagulation. The most
      common cause of secondary pulmonary hypertension is alveolar hypoxia associated
      with chronic lung diseases. Long-term oxygen therapy improves survival and
      partially reverses the development of pulmonary hypertension. In chronic
      thromboembolic pulmonary hypertension, therapy includes anticoagulation and, in
      the case of lower limb venous thrombosis, inferior vena cava filtration. On the
      other hand, selected subsets of patients can undergo thromboendarterectomy. If
      the latter is contraindicated, lung transplantation is the only remaining
      curative treatment. However, lung transplantation should only be performed in end
      stage diseased patients. Inclusion criteria are similar to those applied for
      primary pulmonary hypertension. The respective indications of heart-lung, double
      lung, and single lung transplantation, in primary or chronic thromboembolic
      pulmonary hypertension, remain to be evaluated.

PMID- 8539220
TI  - [Idiopathic segmentary infarction of the greater omentum: an indication for
      celioscopy].

PMID- 8539221
TI  - [Invasive anal carcinoma in a homosexual patient with HIV infection].

PMID- 8539222
TI  - [Blastocystis hominis, a potentially pathogenic parasite frequently identified
      after a travel in tropical regions].

PMID- 8539223
TI  - [Anticardiolipin antibodies and thrombosis].

PMID- 8539224
TI  - Guardians of the wax ... and the patient.

PMID- 8539225
TI  - Overexpression of the c-myc proto-oncogene occurs frequently in uterine sarcomas.
AB  - Overexpression of the c-myc proto-oncogene occurs in carcinoma of the ovary,
      endometrium, and cervix, and is associated with an adverse prognosis, but little
      is known about the pattern of c-myc expression in uterine sarcomas. This study
      investigates the expression of c-myc in uterine smooth muscle tumors and
      malignant mixed mullerian tumors. Twenty-three leiomyosarcomas, 10 leiomyomas,
      and 9 malignant mixed mullerian tumors were examined for c-myc overexpression by
      immunohistochemistry. Differences in mitotic rate and in survival were compared
      in c-myc positive and negative cases of leiomyosarcoma. Overexpression of c-myc
      was seen in 6/12 leiomyomas, 11/23 leiomyosarcomas, and 9/9 malignant mixed
      mullerian tumors. Positive staining was restricted to a perinuclear location in
      all of the leiomyomas and one leiomyosarcoma. Diffuse cytoplasmic staining was
      seen in the remaining 10 positive leiomyosarcomas. Positive staining was seen in
      both epithelial and stromal elements of malignant mixed mullerian tumors,
      including homologous and heterologous areas of stromal differentiation. There was
      no significant difference in mitotic rate or in survival between c-myc positive
      and negative cases of leiomyosarcoma. Overexpression of c-myc occurs in many
      uterine leiomyosarcomas and the majority of malignant mixed mullerian tumors.
      Overexpression of c-myc also occurs in benign uterine smooth muscle tumors but
      with a different pattern than that seen in malignant tumors. This overexpression
      does not correlate with survival and the significance of overexpression of c-myc
      in these tumors is unclear.

PMID- 8539226
TI  - Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a
      simplified system for grading.
AB  - Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas,
      it is difficult to test standardized treatment protocols for individual tumor
      entities. Grading has been used successfully to predict outcome of adult
      sarcomas, but pediatric soft tissue tumors display a notable difference in
      clinical behavior when compared to older patients. To test systematically a
      standardized treatment strategy for pediatric nonrhabdomyosarcomastous soft
      tissue sarcomas devised by the Pediatric Oncology Group, the authors devised a
      grading schema using concepts of adult grading systems and integrating the unique
      clinical and morphologic features of pediatric sarcomas. Three grading tiers were
      devised: Grade I, which includes certain pediatric tumors with little propensity
      for malignancy; Grade II, which is composed of tumors excluded from Grades I or
      III by virtue of histologic diagnosis and having <5 mitoses/10 high-power fields
      or <15% geographic necrosis; and Grade III, which comprises certain tumors known
      to be clinically aggressive by virtue of histologic diagnosis and non-Grade I
      tumors with >4 mitoses/10 high-power fields or > 15% necrosis. An initial
      retrospective analysis on a series of lesions treated at a single institution
      indicated a strong predictive value for grading. Subsequent prospective studies
      by the Pediatric Oncology Group continue to verify the prognostic value of
      pediatric nonrhabdomyosarcomatous soft tissue sarcoma grading, and studies on
      individual pediatric nonrhabdomyosarcomatous soft tissue sarcomas, such as
      synovial sarcoma, also indicate the relatively poor outcome of higher grade
      lesions. Grade can be used to predict outcome of pediatric
      nonrhabdomyosarcomatous soft tissue sarcomas and to devise treatment strategies
      for experimental protocols.

PMID- 8539227
TI  - Spindle cell malignant lymphoepithelial lesion of the parotid gland: clinical,
      light microscopic, ultrastructural, and in situ hybridization findings in one
      case.
AB  - Malignant lymphoepithelial lesions (MLEL) are rare tumors of the salivary glands
      that show high incidence in Inuit Canadians, Alaskans, and Greenland Eskimos. The
      tumors are usually anaplastic or poorly differentiated squamous cell carcinomas.
      Focal spindle cell elements have been rarely reported. The tumors have been
      epidemiologically linked to Epstein-Barr virus infection. We present a case of
      malignant lymphoepithelial lesion showing exclusive spindle cell morphology. The
      patient is a 44-year-old male Inuit Canadian who presented with a long-standing
      history of a left parotid mass. The mass did not show evidence of rapid growth or
      facial nerve involvement. Parotidectomy was performed. The tumor was
      histologically composed of spindle cells nodules in a background of lymphocytes.
      The spindle cells showed no evidence of cytologic atypia but were mitotically
      active. Immunohistochemical staining for low-molecular-weight cytokeratin was
      only focally positive. The differential diagnosis included a mesenchymal neoplasm
      and malignant lymphoepithelial lesion. Electron microscopic examination confirmed
      the squamous nature of the neoplasm. Intracytoplasmic viral particles were also
      identified ultrastructurally. In situ hybridization for Epstein-Barr virus mRNA
      using a 30-base oligonucleotide probe specific for the EBER-1 gene showed very
      high level of expression in the tumor cells. No expression was noted in the
      adjacent parotid gland tissue. Our findings confirm the squamous nature of
      malignant lymphoepithelial lesions despite the spindle cell morphology
      occasionally seen in these neoplasms. They also confirm the strong role of
      Epstein-Barr virus infection in the pathogenesis of these tumors. This may have
      further diagnostic and therapeutic implications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539228
TI  - Histopathologic effects of laser radiation on the human prostate.
AB  - High levels of applied laser irradiation to the prostate will carbonize or
      vaporize tissue, and may cause explosive expansion of superheated tissue water.
      Lower levels, used most often to relieve obstruction caused by benign prostatic
      hypertrophy, will cause coagulation necrosis. This effect is apparent within 1 h
      of application. In contrast to the canine, in which laser-coagulated prostate
      sloughs in 2 to 3 weeks leaving a smooth cavity, in the human necrotic tissue is
      sloughed irregularly over a period ranging up to 12 weeks. This difference is
      attributed to the dominantly glandular nature of the canine prostate, and the
      dense fibromuscular composition of the human prostate stroma. Sloughing is
      accomplished by surface liquefaction, cavitation of the necrotic coagulum, and to
      a lesser degree, formation of granulation tissue at the margins. As often occurs
      at the margin of spontaneous infarcts in the prostate, squamous metaplasia may be
      prominent at the margins of laser-induced coagulation necrosis.

PMID- 8539229
TI  - Nephrogenic adenoma of the urinary tract: a review of the microscopic appearance
      of 80 cases with emphasis on unusual features.
AB  - A detailed review of the microscopic features of 80 nephrogenic adenomas of the
      urinary tract was undertaken. The lesions occurred in patients who ranged in age
      from 15 to 94 (average, 52) years. There was a 2:1 male/female ratio. Fifty-five
      percent of the lesions occurred in the urinary bladder, 41% in the urethra, and
      4% in the ureter. The most common microscopic pattern, present in 96% of the
      cases, was tubular. The tubules were usually small, hollow, and round, but some
      were solid and occasionally elongated. Their arrangement varied from orderly,
      sometimes laminar, to pseudoinfiltrative. A basement membrane was appreciable
      around the tubules in 25% of the cases but was rarely prominent. In two prostatic
      urethral cases tubules involved the fibromuscular prostatic stroma. A cystic
      pattern was seen in 72% of the cases. The tubules and cysts most commonly
      contained eosinophilic secretion but in 25% of the cases the secretion was
      basophilic. In 12% of the cases some of the tubules were tiny and when they
      contained basophilic secretion occasionally mimicked signet-ring cells. The third
      most frequent pattern, seen in 65% of the cases, was papillary to polypoid.
      Edematous polyps were commonest but thin, delicate filiform papillae were present
      in 10% of the cases. A complex branching pattern with prominent budding of small
      papillae was seen in three cases. The papillary-polypoid pattern was usually
      associated with a tubular component but in three cases it was pure. The final
      pattern, present in 14% of the cases, was diffuse, but it was prominent in only
      one case.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539230
TI  - "Adenoid cystic" and basaloid carcinomas of the ovary: evidence for a surface
      epithelial lineage. A report of 12 cases.
AB  - Twelve ovarian neoplasms resembling salivary gland carcinomas and cutaneous basal
      cell carcinomas were studied and assigned to two groups: six with an exclusive or
      conspicuous component resembling adenoid cystic carcinoma and six with an
      exclusive or predominant component resembling basal cell carcinoma. The patients
      whose tumors simulated an adenoid cystic carcinoma presented at 60 to 78 (mean,
      67) years of age. The adenoid cystic-like pattern was present in the primary
      ovarian tumor in five cases and four of these tumors had an additional surface
      epithelial-stromal component (serous adenocarcinoma in two, endometrioid
      adenocarcinoma in one, and mixed clear cell/endometrioid adenocarcinoma in one).
      The one patient with a Stage Ia tumor was free of disease at 37 months. Of the
      four patients whose tumors were Stage IIIc, two died of tumor at 13 and 123
      months, respectively; another was alive with tumor at 27 months; and one was lost
      to follow-up. In the sixth case, an adenoid cystic-like pattern was present in a
      recurrent tumor in a patient from whom an ovarian endometrioid adenocarcinoma had
      been excised 11 years earlier. The patients whose carcinomas were predominantly
      or entirely basaloid presented at 19 to 65 (mean, 49) years of age. Three of
      these tumors had prominent squamous differentiation and gland formation,
      suggesting a relation to endometrioid carcinoma; three other tumors had an
      ameloblastoma-like pattern, with focal squamous differentiation in one, and a
      minor component of endometrioid adenocarcinoma adjacent to another. The four
      patients in the basaloid carcinoma group with Stage Ia tumors were alive without
      tumor at 16 to 71 (mean, 35) months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539231
TI  - Thymolipoma: clinicopathologic review of 33 cases.
AB  - The clinical, radiologic, and pathologic features of 33 cases of mediastinal
      thymolipoma are presented. The patients' ages ranged from 2 to 64 (mean, 33)
      years; 18 were male and 15 were female. Clinically, the majority of patients (18
      cases) were asymptomatic. Five patients presented with upper respiratory
      symptoms, two patients presented with chest pain, two patients with myasthenia
      gravis, and one patient with a neck mass; no clinical information was available
      in four patients. All the tumors were located in the anterior mediastinum and in
      all cases complete surgical resection of the mass was accomplished.
      Radiographically, 20 cases showed an anterior mediastinal tumor; when available,
      computed tomography and/or magnetic resonance imaging demonstrated a mixture of
      fat and soft tissue elements in these tumors. Grossly, the tumors were described
      as fairly well-circumscribed, soft, yellowish, fatty tumors with focal solid
      areas. The tumors varied in size from 4.5 to 36 cm in greatest dimension.
      Histologically, they were characterized by the presence of abundant mature
      adipose tissue admixed with areas containing remnants of thymic tissue. The fatty
      tissue consisted of mature adipocytes devoid of atypia, and the thymic tissue
      component varied from strands of atrophic thymic epithelium to large areas
      containing thymic parenchyma showing the typical mixed epithelial/lymphocytic
      architecture with numerous Hassall's corpuscles. Areas of calcification and
      cystic degeneration of Hassall's corpuscles were quite prominent in a large
      number of cases. Our study shows that thymolipomas span the age ranges from the
      very young to adult individuals with a slight prevalence for patients under the
      age of 40.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539232
TI  - Comparison of different immunohistochemical methods in the assessment of
      angiogenesis: lack of prognostic value in a group of 77 selected node-negative
      breast carcinomas.
AB  - There is evidence that tumor angiogenesis, as detected by immunohistochemical
      staining of endothelium, is of prognostic significance in breast cancer. However,
      little attention has been paid to possible differences between antibodies or to
      quantitation of the stained microvessels. We compared three endothelial cell
      antibodies [anti-human von Willebrand factor (anti-VWF, also termed factor VIII),
      anti-CD31, and anti-CD34] in archival paraffin-embedded specimens. Anti-CD34 and
      anti-VWF showed better staining performances than anti-CD31, although the
      staining results with different antibodies were comparable. Two different methods
      of microvessel quantitation (the highest microvessel count and percentage
      microvessel area) were evaluated and also showed significant correlation. From a
      retrospective database (n = 1000), 77 axillary node-negative invasive ductal
      breast carcinomas were selected on the basis of clinical outcome to maximize the
      prognostic power of the sample set (37 died due to a metastatic breast carcinoma,
      40 showed no recurrence during 8-yr follow-up). Microvessel quantitations were
      related to flow cytometric DNA ploidy, c-erb-B-2 overexpression, and estrogen
      receptor status of the tumor. Surprisingly, neither highest microvessel counts
      nor microvessel area measurements quantitated with anti-CD34 or anti-VWF
      immunohistochemistry were able to discriminate between favorable and unfavorable
      outcome patients. Thus, our results suggest that further evidence is still needed
      on tumor angiogenesis immunohistochemistry before it can be adopted as a
      prognostic marker in routine, clinical practice.

PMID- 8539233
TI  - Enteropathy-associated T-cell lymphoma in the West of Ireland: low-frequency of
      Epstein-Barr virus in these tumors.
AB  - The Epstein-Barr virus has been implicated in the etiology of endemic Burkitt's
      lymphoma, post-transplant lymphoma, large-cell anaplastic CD30 (Ki-1)-positive
      lymphoma, and in many T-cell lymphomas. A recent report has found Epstein-Barr
      virus genome in association with 4 of 11 cases (36%) of enteropathy-associated T
      cell lymphoma. In a retrospective study, we have characterized 22 consecutive
      cases of enteropathy-associated T-cell lymphoma from the West of Ireland where
      celiac disease is endemic. All cases were immunophenotyped with T- and B-cell
      markers including the anaplastic large-cell lymphoma marker CD30 or Ki-1.
      Nineteen cases were studied for latent membrane protein expression and 16 for
      Epstein-Barr virus small RNAs by in situ hybridization using EBER
      oligonucleotides on routinely processed sections. Only 1 of 16 cases (6%) showed
      Epstein-Barr virus in tumor cells and no cases stained with latent membrane
      protein. Eight of 22 cases (36%) including the EBER-positive case were positive
      for CD30. These results suggest that the Epstein-Barr virus does not commonly
      play a role in the pathogenesis of enteropathy-associated T-cell lymphoma from
      this area.

PMID- 8539234
TI  - Molecular and immunohistochemical evaluation of epidermal growth factor receptor
      and c-erb-B-2 gene product in transitional cell carcinomas of the urinary
      bladder: a study in Greek patients.
AB  - In this study, the expression of epidermal growth factor receptor (EGFr) and c
      erb-B-2 was evaluated in 35 formalin-fixed, paraffin-embedded cases of
      transitional cell carcinomas of the urinary bladder (TCCs). EGFr and c-erb-B-2
      expression was assessed with immunohistochemistry, and molecular analysis of the
      respective genes was performed with the differential polymerase chain reaction.
      The results were statistically analyzed in relationship to histologic grade,
      stage, and clinical outcome. Strong cytoplasmic expression of the EGFr using the
      polyclonal antibody Ab-4 was found in three (25%) Grade 2 and eight (67%) Grade 3
      TCCs (P < 0.01). Two Grade 2 (17%) and 11 (92%) Grade 3 TCCs strongly expressed
      the anti-c-erb-B-2 Ab-3 antibody. None of Ta/T1 TCCs cases showed strong
      expression against EGFr, in contrast to c-erb-B-2 where two cases (18%) were
      found to express an intense immunosignal. Eleven (85%) T2/T3 cases showed strong
      positivity either against EGFr or c-erb-B-2 (P < 0.001). Eleven patients died
      within 12 months after the diagnosis, and all of them showed strong expression of
      EGFr and c-erb-B-2. Amplification of EGFr and c-erb-B-2 genes was identified in
      one (3%) and four (11%) TCCs cases, respectively. All patients with amplified
      genes died within 12 months from the date of diagnosis. Our results indicate that
      simultaneous expression of EGFr and c-erb-B-2 occurs in TCCs, is related to the
      histologic grade and the stage of the disease, and denotes aggressive biologic
      behavior.

PMID- 8539235
TI  - t(9;22)(q22-31;q11-12) is a consistent marker of extraskeletal myxoid
      chondrosarcoma: evaluation of three cases.
AB  - Three cases of extraskeletal myxoid chondrosarcoma with typical histologic and
      ultrastructural features were investigated cytogenetically. All three cases
      showed a reciprocal chromosome translocation characterized as t(9;22)(q22-31)(q11
      12), thus confirming the findings in three previously karyotyped cases of
      extraskeletal myxoid chondrosarcoma in the literature. These data add
      significantly to the evidence of t(9;22) being diagnostic for extraskeletal
      myxoid chondrosarcoma. Other previously published cases with a range of complex
      karyotypes were less well defined morphologically. In cases with limited
      diagnostic material this karyotype might facilitate distinction from myxoid
      liposarcoma, which consistently shows t(12;16). Clear cell sarcoma, Ewing's
      sarcoma/primitive neuroectodermal tumor, and desmoplastic round cell tumor also
      show involvement of chromosome 22 with formation of a hybrid gene between the
      Ewing's sarcoma gene on band q12 and a transcription factor gene. Whether
      rearrangement of the Ewing's sarcoma gene is also present in extraskeletal myxoid
      chondrosarcoma is not clear at present. Cloning of the (9;22) translocation might
      provide important clues to the pathogenesis of this type of chondrosarcoma.

PMID- 8539236
TI  - Cutaneous lymphoma-simulating Merkel cell carcinoma-molecular genetic
      demonstration of a clonal disease with divergent immunophenotypes.
AB  - Merkel cell carcinoma and malignant lymphoma are important differential diagnoses
      for undifferentiated cutaneous round cell tumors and immunohistochemistry is
      instrumental in their evaluation. We describe a case of a 73-year-old man who had
      cutaneous large cell lymphoma in the right leg (immunophenotype CD45+, CD19+,
      CD20+ CD22+, lambda clonal, cytokeratin-, NSE-) and lymphoma in left leg
      simulating Merkel cell carcinoma showing absence of leukocyte antigens (CD45-,
      CD20-, no light chains) and focal expression of keratin and NSE. However,
      analysis of polymerase chain reaction amplification products of DNA extracted
      from both lesions showed two amplifiable sharp bands indicating clonal
      rearrangements of both alleles of the immunoglobulin heavy chain. Cloning and
      sequencing of the products from left and right leg lesions showed either 100%
      homology (one band), or close similarity (the other band), indicating that both
      tumors were derived from the same B-cell lymphoma clone. This case shows the
      value of polymerase chain reaction and sequencing in analyzing the ultimate
      nature of lymphoproliferations and illustrates the potential limitations of
      immunophenotyping.

PMID- 8539237
TI  - DNA ploidy of hydatidiform moles and nonmolar conceptuses: a study using flow and
      tissue section image cytometry.
AB  - This study was performed to investigate the role of DNA cytometry in the
      evaluation of molar and nonmolar pregnancies. DNA ploidy analysis was performed
      on paraffin-embedded tissue from 53 molar (35 complete, 18 partial) and 24
      nonmolar (13 hydropic, 11 nonhydropic) conceptuses. Nuclear suspensions were
      analyzed by both flow and image cytometry and there was excellent correlation
      (96%) in the classification of DNA diploid, triploid, and tetraploid cases using
      these two methods. DNA ploidy analysis revealed a high proportion of tetraploid
      nonmolar conceptuses (42%) and complete moles (47%). The majority of partial
      moles were triploid (89%). Tissue sections from all cases were also studied by
      image cytometry to identify the cellular subpopulations (decidua, villous stromal
      cells, inner trophoblast, and extravillous trophoblast) with abnormal DNA
      content. In the triploid cases, all of the villous cell subtypes had an abnormal
      DNA content consistent with the development of partial moles from a triploid
      conceptus. In contrast, the majority of tetraploid cases showed high
      proliferative activity of the extravillous trophoblast whereas the other villous
      cell subtypes were diploid. These results suggest that tetraploid complete moles
      may arise from a diploid conceptus with the development of tetraploidy related to
      polyploidization of the hyperplastic extravillous trophoblast. Tissue section
      image cytometric DNA analysis can aid in our interpretation of ploidy results and
      our understanding of the biology of molar pregnancies.

PMID- 8539238
TI  - Ringed sideroblasts: a frequent observation after bone marrow transplantation.
AB  - Dyserythropoiesis after bone marrow transplantation is common, but the presence
      of ringed sideroblasts (RS) has not been evaluated fully. To examine for RS, a
      combined silver and Perls' Prussian blue stain, shown previously to be more
      sensitive for detecting RS than Perls' Prussian blue stain alone, was used on
      post-transplant marrow aspirate sections from 39 patients who received marrow
      transplants (allogeneic, 28; autologous, 11) for a variety of disorders. Marrow
      aspirate sections were available for comparison from 11 of these patients before
      any treatment as well as from five patients with normal marrows and normal
      peripheral blood cell counts. Aspirates were not performed on donor marrows. By
      the modified silver stain, RS were present in 34 (87%) patients whose marrows
      were sampled 0.5 to 39 (median, 1.5) months post-transplant including 10 of 11
      patients with autologous transplants (no graft versus host disease prophylaxis).
      In contrast, seven of 36 (19%) of these marrows contained RS when stained with
      Perls' reaction alone. Only one of 11 pretransplant marrows and none of five
      normal marrows contained RS when stained by either method. These results
      demonstrate that RS are present in most post-transplant marrows even beyond the
      usual period of reconstitution (28 days), and this finding can be included among
      the features of dyserythropoiesis seen after transplantation. RS apparently are
      not related to pretransplant pathology or post-transplant therapy. This study
      also confirms previous observations that modified silver stains are more
      sensitive for detecting RS than Perls' Prussian blue stain.

PMID- 8539239
TI  - Recognition of atypical reserve cell hyperplasia in cervical smears and its
      diagnostic significance.
AB  - In this study, the histological, cytological, and electron microscopical features
      of cervical atypical reserve cell hyperplasia are presented. The most important
      feature of atypical reserve cells in smears is the absence of cytoplasm. Thus,
      they must be recognized on the absence and not on the presence of a feature,
      which makes identifying these cells a controversial issue. These stripped nuclei
      are erroneously believed to be degenerated cylindrical cells, and accordingly are
      ignored. The atypical reserve cell nuclei are easily damaged in the smear
      process; however, the MIB-1 staining shows that these disrupted nuclei are
      derived from proliferating cells. In a follow-up histological study of cases
      diagnosed as mild dysplasia in a smear, it was found that the presence of MIB-1
      positive staining atypical reserve cells was closely related to the development
      of carcinoma in situ. Recognizing the atypical reserve cells and observing their
      proliferating activity in a smear might prove to be more important than focusing
      on the better-known dysplastic cells.

PMID- 8539240
TI  - Recommendations for the reporting of resected primary lung carcinomas.
      Association of Directors of Anatomic and Surgical Pathology.

PMID- 8539241
TI  - Consensus preferred hydration sites in six FKBP12-drug complexes.
AB  - A set of consensus hydration sites for the FK506-FKBP12 complex are derived by
      comparing six FKBP12-drug complexes. These hydration sites include a subset of
      the observed water molecules plus some sites that are occupied by neighboring
      protein atoms in the FK506-FKBP12 crystal structure. Two hydration prediction
      algorithms, AUTO-SOL and AQUARIUS2, showed significant increases in apparent
      efficacy using these consensus water sites, suggesting that our proposed set of
      consensus hydration sites is truly a better representation of the hydration
      properties of FKBP12 in solution. Predictably, the consensus hydration sites
      include all buried water molecules. Otherwise, the features of solvation sites
      included in the consensus list versus those discarded reveal no distinctive
      features that would allow them to be selected unambiguously without reference to
      multiple crystal forms. We suggest that analyses such as this one are a crucial
      prelude to any theoretical analysis aimed at understanding hydration properties.

PMID- 8539242
TI  - Characterization of crystals of the thermostable DNA polymerase I from Thermus
      aquaticus.
AB  - Thermus aquaticus DNA polymerase I is an enzyme that is of both physiological and
      technological interest. It carries out template-directed polymerization of DNA at
      elevated temperatures and is widely used in polymerase chain reaction (PCR). We
      have obtained crystals of the enzyme that diffracts X-rays to at least 3.0 A
      resolution in a cubic space group. Determination of the three-dimensional
      structure of the native enzyme along with those of relevant complexes will
      greatly enhance our knowledge of molecular events involved in DNA replication,
      will permit improvements in PCR, and will add to our knowledge of the structural
      bases of thermostability in proteins.

PMID- 8539243
TI  - Crystallization and preliminary X-ray diffraction studies of complexes between an
      influenza hemagglutinin and Fab fragments of two different monoclonal antibodies.
AB  - Fab fragments from two different monoclonal antibodies (BH151 and HC45) which
      bind to the same antigenic region of the influenza hemagglutinin were
      crystallized as complexes with the hemagglutinin. The complexes crystallize in
      PEG 600, pH 6.0, and PEG 2000, pH 8.5, respectively. Both crystals belong to
      space group P321, with very similar unit cell dimensions.

PMID- 8539244
TI  - Crystallization and X-ray diffraction data of the cleaved form of plasminogen
      activator inhibitor-1.
AB  - To characterize the structural requirements for the conformational flexibility in
      plasminogen activator inhibitor-1 (PAI-1) we have crystallized human PAI-1,
      carrying a mutation which stabilizes PAI-1 in its substrate form. Crystallization
      was performed by the hanging drop diffusion method at pH 8.5 in the presence of
      19% (w/v) polyethyleneglycol 4000 as a precipitant. The crystals appear after 3
      days at 23 degrees C and belong to the monoclinic space group C2 with cell
      dimensions of a = 151.8 A, b = 47.5 A, c = 62.7 A, and beta = 113.9 degrees, and
      one molecule in the asymmetric unit. The X-ray diffraction data set contains data
      with a limiting resolution of 2.5 A. Biochemical analysis of the redissolved
      crystals indicated that during the crystallization process, cleavage had occurred
      in the active site loop at the P1-P1' position. The availability of good-quality
      crystals of the cleaved form of this serpin will allow its three-dimensional
      structure to be solved and will provide detailed information on the structure
      function relationship in PAI-1.

PMID- 8539245
TI  - Zinc binding in proteins and solution: a simple but accurate nonbonded
      representation.
AB  - Force field parameters that use a combination of Lennard-Jones and electrostatic
      interactions are developed for divalent zinc and tested in solution and protein
      simulations. It is shown that the parameter set gives free energies of solution
      in good agreement with experiment. Molecular dynamics simulations of
      carboxypeptidase A and carbonic anhydrase are performed with these zinc
      parameters and the CHARMM 22 beta all-atom parameter set. The structural results
      are as accurate as those obtained in published simulations that use specifically
      bonded models for the zinc ion and the AMBER force field. The inclusion of longer
      range electrostatic interactions by use of the Extended Electrostatics model is
      found to improve the equilibrium conformation of the active site It is concluded
      that the present parameter set, which permits different coordination geometries
      and ligand exchange for the zinc ion, can be employed effectively for both
      solution and protein simulations of zinc-containing systems.

PMID- 8539246
TI  - Crystallization of a soluble, catalytically active form of Escherichia coli
      leader peptidase.
AB  - Leader peptidase, a novel serine protease in Escherichia coli, catalyzes the
      cleavage of the amino-terminal leader sequences from exported proteins. It is an
      integral membrane protein containing two transmembrane segments with its carboxy
      terminal catalytic domain residing in the periplasmic space. Here, we report a
      procedure for the purification and the crystallization of a soluble non-membrane
      bound form of leader peptidase (delta 2-75). Crystals were obtained by the
      sitting-drop vapor diffusion technique using ammonium dihydrogen phosphate as the
      precipitant. Interestingly, we have found that the presence of the detergent
      Triton X-100 is required to obtain crystals sufficiently large for X-ray
      analysis. The crystals belong to the tetragonal space group P4(2)2(1)2, with unit
      cell dimensions of a = b = 115 A and c = 100 A, and contain 2 molecules per
      asymmetric unit. This is the first report of the crystallization of a leader (or
      signal) peptidase.

PMID- 8539247
TI  - Crystallization and preliminary crystallographic analysis of recombinant abrin-a
      A-chain with ribosome inactivating activity.
AB  - Crystals have been obtained for a recombinant abrin-a A-chain produced by E.
      coli. The crystals were grown using PEG6000 as the precipitating agent. The
      crystals belong to an orthrhombic space group (P2(1)2(1)2(1)) and diffract to 1.7
      A.

PMID- 8539248
TI  - Circular dichroism of the parallel beta helical proteins pectate lyase C and E.
AB  - The pectate lyases, PelC and PelE, have an unusual folding motif, known as a
      parallel beta-helix, in which the polypeptide chain is coiled into a larger helix
      composed of three parallel beta-sheets connected by loops having variable lengths
      and conformations. Since the regular secondary structure consists almost entirely
      of parallel beta-sheets these proteins provide a unique opportunity to study the
      effect of parallel beta-helical structure on circular dichroism (CD). We report
      here the CD spectra of PelC and PelE in the presence and absence of Ca2+, derive
      the parallel beta-helical components of the spectra, and compare these results
      with previous CD studies of parallel beta-sheet structure. The shape and
      intensity of the parallel beta-sheet spectrum is distinctive and may be useful in
      identifying other proteins that contain the parallel beta-helical folding motif.

PMID- 8539249
TI  - Rigid domains in proteins: an algorithmic approach to their identification.
AB  - A rigid domain, defined here as a tertiary structure common to two or more
      different protein conformations, can be identified numerically from atomic
      coordinates by finding sets of residues, one in each conformation, such that the
      distance between any two residues within the set belonging to one conformation is
      the same as the distance between the two structurally equivalent residues within
      the set belonging to any other conformation. The distance between two residues is
      taken to be the distance between their respective alpha carbon atoms. With the
      methods of this paper we have found in the deoxy and oxy conformations of the
      human hemoglobin alpha 1 beta 1 dimer a rigid domain closely related to that
      previously identified by Baldwin and Chothia (J. Mol. Biol. 129: 175-220, 1979).
      We provide two algorithms, both using the difference-distance matrix, with which
      to search for rigid domains directly from atomic coordinates. The first finds all
      rigid domains in a protein but has storage and processing demands that become
      prohibitively large with increasing protein size. The second, although not
      necessarily finding every rigid domain, is computationally tractable for proteins
      of any size. Because of its efficiency we are able to search protein
      conformations recursively for groups of non-intersecting domains. Different
      protein conformations, when aligned by superimposing their respective domain
      structures, can be examined for structural differences in regions complementing a
      rigid domain.

PMID- 8539250
TI  - Structure and internal dynamics of the bovine pancreatic trypsin inhibitor in
      aqueous solution from long-time molecular dynamics simulations.
AB  - Structural and dynamic properties of bovine pancreatic trypsin inhibitor (BPTI)
      in aqueous solution are investigated using two molecular dynamics (MD)
      simulations: one of 1.4 ns length and one of 0.8 ns length in which atom-atom
      distance bounds derived from NMR spectroscopy are included in the potential
      energy function to make the trajectory satisfy these experimental data more
      closely. The simulated properties of BPTI are compared with crystal and solution
      structures of BPTI, and found to be in agreement with the available experimental
      data. The best agreement with experiment was obtained when atom-atom distance
      restraints were applied in a time-averaged manner in the simulation. The
      polypeptide segments found to be most flexible in the MD simulations coincide
      closely with those showing differences between the crystal and solution
      structures of BPTI.

PMID- 8539251
TI  - Stability of TEM beta-lactamase mutants hydrolyzing third generation
      cephalosporins.
AB  - The stability properties of six natural mutants of the TEM-1 beta-lactamase have
      been studied. The glutamate to lysine substitution at positions 104 and 240
      stabilize the enzyme. Conversely, the G238S mutant's decreased stability might
      reflect an altered conformation of the active site and thus be related to the
      modified substrate profile. The relative stability of the R164S and R164H mutants
      is explained by the formation of a hydrogen bond between these residues and Asp
      179 conferring a somewhat different structure to the omega loop and thus also
      explaining the extended substrate profile of these mutants. The loss of stability
      of the R164H mutant with increasing pH values can be explained by the titration
      of a hydrogen bond between the N delta of His-164 and the O delta of Asp-179. The
      properties of the G238S + E104K double mutant which is the most active against
      third-generation cephalosporins result from a balance of destabilizing and
      stabilizing substitutions, and their effects seem to be additive. The behavior of
      the R164S + E240K mutant might be explained on the basis of a similar
      compensation phenomenon.

PMID- 8539252
TI  - Local moves: an efficient algorithm for simulation of protein folding.
AB  - We have enhanced genetic algorithms and Monte Carlo methods for simulation of
      protein folding by introducing "local moves" in dihedral space. A local move
      consists of changes in backbone dihedral angles in a sequential window while the
      positions of all atoms outside the window remain unchanged. We find three
      advantages of local moves: (1) For some energy functions, protein conformations
      of lower energy are found; (2) these low energy conformations are found in fewer
      steps; and (3) the simulations are less sensitive to the details of the annealing
      protocol. To distinguish the effectiveness of local move algorithm from the
      complexity of the energy function, we have used several different energy
      functions. These energy functions include the Profile score (Bowie et al.,
      Science 253:164-170, 1991), the knowledge-based energy function used by Bowie and
      Eisenberg 1994 (Proc. Natl. Acad. Sci. U.S.A. 91:4434-4440, 1994), two energy
      terms developed as suggested by Sippl and coworkers (Hendlich et al., J. Mol.
      Biol. 216:167-180, 1990), and AMBER (Weiner and Kollman, J. Comp. Chem. 2:287
      303, 1981). Besides these energy functions we have used three energy functions
      that include knowledge of the native structures: the RMSD from the native
      structure, the distance matrix error, and an energy term based on the distance
      between different residue types called DBIN. In some of these simulations the
      main advantage of local moves is the reduced dependence on the details of the
      annealing schedule. In other simulations, local moves are superior to other
      algorithms as structures with lower energy are found.

PMID- 8539253
TI  - Effects of cavity-creating mutations on conformational stability and structure of
      the dimeric 4-alpha-helical protein ROP: thermal unfolding studies.
AB  - The structural and energetic perturbations caused by cavity-creating mutations
      (Leu-41-->Val and Leu-41-->Ala) in the dimeric 4-alpha-helical-bundle protein ROP
      have been characterized by CD spectroscopy and differential scanning calorimetry
      (DSC). Deconvolution of the CD spectra showed a decrease in alpha-helicity as a
      result of the amino acid exchanges that follows qualitatively the overall
      decrease in conformational stability. Transition enthalpies are sensitive probes
      of the energetic change associated with point mutations. delta H zero values at
      the respective transition temperatures, T 1/2 (71.0, 65.3, and 52.9 degrees C at
      0.5 mg/ml) decrease from 580 +/- 20 to 461 +/- 20 kJ/(mol of dimer) and 335 +/-
      20 kJ/(mol of dimer) for wild-type ROP (Steif, C., Weber, P., Hinz, H.-J.,
      Flossdorf, J., Cesareni, G., Kokkinidis, M. Biochemistry 32:3867-3876, 1993),
      L41V, and L41A, respectively. The conformational stabilities at 25 degrees C
      expressed by the standard Gibbs energies of denaturation, delta GzeroD, are 71.7,
      61.1, and 46.1 kJ/(mol of dimer). The corresponding transition enthalpies have
      been obtained from extrapolation using the cDp(T) and cNp(T) functions. Their
      values at 25 degrees C are 176.3, 101.9, and 141.7 kJ/(mol of dimer) for wild
      type ROP, L41V, and L41A, respectively. When the stability perturbation resulting
      from the cavity creating mutations is referred to the exchange of 1 mol of CH2
      group, the average delta delta GzeroD value is -5.0 +/- 1 kJ/(mol of CH2 group).
      This decrease in conformation stability suggests that dimeric ROP exhibits the
      same susceptibility to Leu-->Val and Leu-->Ala exchanges as small monomeric
      proteins. Careful determinations of the partial specific heat capacities of wild
      type and mutated protein solutions suggest that the mutational effects are
      predominantly manifested in the native rather than the unfolded state.

PMID- 8539255
TI  - Directory of members.

PMID- 8539254
TI  - Protein conformational landscapes: energy minimization and clustering of a long
      molecular dynamics trajectory.
AB  - Using energy minimization and cluster analysis, we have analyzed a 1020 ps
      molecular dynamics trajectory of solvated bovine pancreatic trypsin inhibitor.
      Elucidation of conformational substates in this way both illustrates the degree
      of conformational convergence in the simulation and reduces the structural data
      to a tractable subset. The relative movement of structures upon energy
      minimization was used to estimate the sizes of features on the protein potential
      energy surface. The structures were analyzed using their pairwise root-mean
      square C alpha deviations, which gave a global measure of conformational changes
      that would not be apparent by monitoring single degrees of freedom. At time
      scales of 0.1 ps, energy minimization detected sharp transitions between energy
      minima separated by 0.1 A rms deviation. Larger conformational clusters
      containing these smaller minima and separated by 0.25 A were seen at 1 ps time
      scales. Both of these small features of the conformational landscape were
      characterized by movements in loop regions associated with small, correlated
      backbone dihedral angle shifts. On a nanosecond time scale, the main features of
      the protein energy landscape were clusters separated by over 0.7 A rms deviation,
      with only seven of these substates visited over the 1 ns trajectory. These
      substrates, discernible both before and after energy minimization, differ mainly
      in a monotonic pivot of the loop residues 11-18 over the course of the
      simulation. This loop contains lysine 17, which specifically binds to trypsin in
      the active site. The trajectory did not return to previously visited clusters,
      indicating that this trajectory has not been shown to have completely sampled the
      conformational substates available to it. Because the apparent convergence to a
      single region of conformation space depends on both the time scale of observation
      and the size of the conformational features examined, convergence must be
      operationally defined within the context of the simulation.

PMID- 8539256
TI  - Radiation protection and radiation recovery with essential metalloelement
      chelates.
AB  - Understanding essential metalloelement metabolism and its role in tissue
      maintenance and function, as well as the roles of essential metalloelement
      dependent enzymes in responding to injury, offer a new approach to decreasing
      and/or treating radiation injury. This review presents the roles of some
      essential metalloelement-dependent enzymes in tissue maintenance and function,
      and their responses to radiation injury in accounting for radiation protection
      and recovery effects observed for nontoxic doses of essential metalloelement
      compounds. Effects of biochemicals including water undergoing bond radiolysis and
      the effects of free radicals derived from diatomic oxygen account for the acute
      and chronic aspects of radiation injury. Recognized biochemical roles of
      essential metalloelement-dependent enzymes and the observed pharmacological
      effects of small-molecular mass chelates predict the therapeutic usefulness of
      essential metalloelement complexes in decreasing and/or treatment of radiation
      injury. Copper chelates have radiation protection and radiation recovery
      activities and cause rapid recovery of immunocompetency and recovery from
      radiation-induced histopathology. Mice treated with Cu(II)2(3,5
      diisopropylsalicylate)4[Cu (II)2(3,5-DIPS)4] had increased survival and
      corresponding increases in numbers of myeloid and multipotential progenitor cells
      early after irradiation and earlier recovery of immune reactivity. Examination of
      radiation-induced histopathology in spleen, bone marrow, thymus, and small
      intestine also revealed Cu(II)2(3,5-DIPS)4-mediated rapid recovery of radiation
      induced histopathology. Most recently, Fe, Mn, and Zn complexes have also been
      found to prevent death in lethally irradiated mice. These pharmacological effects
      of essential metalloelement chelates can be understood as due to facilitation of
      de novo synthesis of essential metalloelement-dependent enzymes which have roles
      in preventing the accumulation of pathological concentrations of oxygen radicals
      or repairing biochemical damage caused by radiation-induced bond homolysis.
      Essential metalloelement chelates offer a physiological approach to prevention
      and/or treatment of radiation injury.

PMID- 8539257
TI  - The ratio of retinoblastoma (RB) to fos and RB to myc expression during the cell
      cycle.
AB  - The putative transregulatory activity of the RB (retinoblastoma tumor suppressor)
      gene product on the expression of the c-myc and c-fos proteins during the cell
      cycle was assessed in HL-60 promyelocytic leukemia cells. Multiparameter flow
      cytometry was used to simultaneously measure nuclear DNA content, RB protein, and
      MYC or FOS protein per cell. The amount of RB protein per cell increased with
      progression through the cell cycle. As the amount of RB protein increased, the
      ratio of RB to MYC or to FOS protein could be determined per cell as a function
      of cell cycle phase. Although the amount of RB protein per cell increased with
      progression through successive cell cycle phases, during S phase the relative
      rate of increase was not as rapid as that of nuclear DNA. The amount of MYC and
      FOS per cell also increased throughout the cell cycle, but also more slowly than
      DNA during S. The ratio of the amount of RB protein to MYC protein remained
      constant throughout the cell cycle, consistent with putative co-regulation
      suggested by previous studies of promoter structure. In contrast, the ratio of RB
      protein to FOS protein increased with progression through the phases of the cell
      cycle, consistent with a putative negative effect of RB on FOS which was found in
      previous studies with transgenes and reporters. There was no significant change
      in these ratios with myelo-monocytic differentiation. Although MYC and FOS have
      both been implicated as growth-promoting oncogenes putatively transregulated by
      RB, their behavior during the cell cycle relative to RB is thus distinguishable.
      Interestingly, in the case of all three of these putative cell cycle regulatory
      proteins, their cell cycle phase-specific expression levels are consistent with a
      minimum amount per cell that is necessary but not sufficient for progression to
      the next cell cycle phase.

PMID- 8539258
TI  - Sumatriptan (Imitrex) transport by the human placenta.
AB  - Sumatriptan (Imitrex), a selective 5-hydroxytryptamine receptor agonist, has been
      found to be of therapeutic benefit in the acute management of migraine. There is
      no information on the transfer of this agent across the human placenta.
      Accordingly, the current study assessed the transport of this drug across the
      normal term human placenta, using the isolated perfused single cotyledon
      technique. We found that only about 15% of a single dose of the agent placed in
      the maternal reservoir crossed into the fetal compartment over 4 hr. Given the
      average elimination half-life of 2 hr for sumatriptan, it is evident that only
      very small amounts of the agent will cross from mother to fetus after single
      doses of Imitrex. Only the parent drug entered the fetal compartment. Metabolites
      were not detected in the perfusates, but there was evidence of some metabolism of
      sumatriptan in the placenta. The nature of the metabolites has not been
      determined. The mechanism of transfer of the drug across the placenta is passive
      (i.e., the clearance is similar to L-glucose which is passively transported), the
      rate of transfer is equal in both directions (maternal to fetal and in the
      reverse), and the drug does not cross into the fetus against a concentration
      gradient. This passive transport of sumatriptan across the placenta is consistent
      with its molecular weight, its water solubility, and its slow penetration across
      the blood-brain barrier in experimental animals.

PMID- 8539259
TI  - Inhibitors of angiotensin-converting enzyme modulate mitosis and gene expression
      in pancreatic cancer cells.
AB  - The angiotensin-converting enzyme (ACE) inhibitor captopril inhibits mitosis in
      several cell types that contain ACE and renin activity. In the present study, we
      evaluated the effect of the ACE inhibitors captopril and CGS 13945 (10(-8) to 10(
      2) M) on proliferation and gene expression in hamster pancreatic duct carcinoma
      cells in culture. These cells lack renin and ACE activity. Both ACE inhibitors
      produced a dose-dependent reduction in tumor cell proliferation within 24 hr.
      Captopril at a concentration of 0.36 mM and CGS 13945 at 150 microM decreased
      cellular growth rate to approximately half that of the control. Neither drug
      influenced the viability or the cell cycle distribution of the tumor cells. Slot
      blot analysis of mRNA for four genes, proliferation associated cell nuclear
      antigen (PCNA), K-ras, protein kinase C-beta (PKC-beta) and carbonic anhydrase II
      (CA II) was performed. Both ACE inhibitors increased K-ras expression by a factor
      of 2, and had no effect on CA II mRNA levels. Captopril also lowered PCNA by 40%
      and CGS 13945 lowered PKC-beta gene expression to 30% of the control level. The
      data demonstrate that ACE inhibitors exhibit antimitotic activity and
      differential gene modulation in hamster pancreatic duct carcinoma cells. The
      absence of renin and ACE activity in these cells suggests that the antimitotic
      action of captopril and CGS 13945 is independent of renin-angiotensin regulation.
      The growth inhibition may occur through downregulation of growth-related gene
      expression.

PMID- 8539260
TI  - Omega-3 fatty acid-containing liposomes in cancer therapy.
AB  - omega-3 fatty acids are associated with reduced growth and incidence of certain
      cancers, and in this report we demonstrate that a fish oil diet (rich in omega-3
      fatty acids) enhances the longevity of mice bearing the myeloid leukemia T27A. We
      have proposed that the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6 delta
      4,7,10,13,16,19) may induce structural changes in tumor cell plasma membranes
      resulting in reduced tumor growth in vitro. Here, we test whether liposomes
      containing DHA (18:0, 22:6 PC) have antitumor effects in vivo, leading to
      enhanced longevity of the tumor-bearing host. Male BALB/c mice (6-8 weeks old)
      were inoculated intraperitoneally with a T27A tumor dose known to cause 100%
      mortality of syngeneic (BALB/c) mice in less than 2 weeks. Small unilamellar
      vesicles (liposomes) were prepared, composed of phosphatidylcholine (PC) with
      18:0 in the sn-l position and one of the following fatty acids in the sn-2
      position: 18:0, 18:1 omega 9 (oleic), 18:3 omega 3 (alpha-linolenic), 20:4 omega
      6 (arachidonic), 22:6 omega 3 (docosahexaenoic). The liposomes were injected
      intraperitoneally into tumor-bearing mice at various times: concurrently with the
      tumor inoculum, at select times during tumor growth, and when the mice were
      moribund. Mouse survival was then charted. DHA-containing lipid vesicles (18:0,
      22:6 PC) caused a statistically significant increase in survival of the tumor
      bearing mice when compared with 18:0, 18:1 PC. Lipid vesicles of 18:0, 18:0 PC
      showed no benefit, and 18:0, 20:4 PC was not significantly different than 18:0,
      18:1 PC. Lipid vesicles containing a different omega-3 fatty acid, 18:0, 18:3 PC,
      also effectively enhanced tumor-bearing mouse survival. The greatest benefit was
      achieved if either the liposome treatments were spaced throughout the tumor
      growth period, or if the tumor inoculum was suspended in the liposome preparation
      (without further liposome treatments). Neither lipid peroxidation nor prolonged
      inflammatory responses appeared to be pertinent, leaving membrane structural
      changes as a feasible mode of liposome action. With antitumor properties of their
      own, omega-3 fatty acid-containing lipid vesicles may offer an important new
      avenue in combination cancer therapies.

PMID- 8539261
TI  - Regulation of insulin-like growth factor-binding proteins in rats with insulin
      dependent diabetes mellitus.
AB  - As previously reported, activation of the adrenocorticotropic hormone (ACTH)
      adrenal cortical axis in rats with insulin-dependent diabetes mellitus (IDDM)
      reduces their growth and circulating insulin-like growth factor-I (IGF-I) levels
      and induces a resistance to growth hormone (GH) and IGF-I. The studies reported
      herein were conducted to determine whether the pituitary and/or adrenal gland
      influence the changes in basal and GH-stimulated serum concentrations of IGF
      binding proteins (IGFBPs) in rats with IDDM. Male rats were made diabetic by
      injections of streptozotocin. Intact nondiabetic (NonDb), diabetic (Db),
      hypophysectomized diabetic (HxDb), and adrenalectomized diabetic (AxDb) rats were
      injected twice daily with 50 micrograms porcine (p) GH or with 0.9% saline for 2
      weeks following the surgeries. Changes in serum IGFBP concentrations were
      determined by Western ligand- or immuno-blot analysis. Neither IGFBP-5 nor -6 was
      detected in any of the treatment groups. Induction of IDDM increased serum
      concentrations of IGFBP-1 and -2 and reduced those of IGFBP-3 and -4. Although
      serum IGFBP-1 and -2 concentrations remained elevated in the HxDb rats compared
      with the NonDb controls, IGFBP-1 levels were reduced compared with those in the
      Db controls. Serum IGFBP-3 and -4 were reduced to levels below those in Db
      controls. Although IGFBP-3 and -4 concentrations were elevated to normal in AxDb
      rats, the IGFBP-2 concentration was increased above those in both NonDb and Db
      rats and the IGFBP-1 concentration was reduced. Administration of pGH increased
      serum IGFBP-4 concentrations in all groups and IGFBP-3 concentrations in all
      groups except the Db. In addition, pGH reduced the concentration of IGFBP-1 in
      HxDb rats and nearly abolished it in AxDb rats, but had no effect on IGFBP-1
      concentration in NonDb or Db rats. Administration of corticosterone (B; 25
      micrograms/ml of 0.9% saline drinking water) to AxDb rats restored Db-like
      profiles of all IGFBPs. The refractoriness of Db rats to pGH is associated with a
      failure of the hormone to elevate IGFBP-2 and -3 titers and to reduce those of
      IGFBP-1. Adrenal B production appears to be responsible for this resistance to
      GH. However, the elevated IGFBP-2 concentration in Db rats does not appear to be
      due to B or any other pituitary-controlled or -derived factors. Impaired growth
      was associated with substantially reduced IGFBP-3 concentrations and elevated
      IGFBP-1, whereas growth restoration was associated with the opposite changes.

PMID- 8539262
TI  - Influenza viral infections enhance sleep in mice.
AB  - Sleepiness is a common perception during viral infection. Nevertheless, very
      little is known about the effects of viral infection on sleep. The aim of the
      present study was to test whether sleep was altered by influenza viral infection
      in mice. After 2-3 days of baseline sleep recordings, Swiss-Webster mice were
      infected intranasally with a lethal (H1N1) or a nonlethal (H3N2) strain of
      influenza virus. Sleep was recorded again for an additional 3 days. Non-rapid eye
      movement sleep (NREMS) was dramatically increased after inoculation of the H1N1
      virus with a latency about 16 hr. Rapid eye movement sleep (REMS) was
      significantly suppressed after a long latency. Both changes lasted until the end
      of the recording and occurred in both young (35-day-old) and adult (90- to 100
      day-old) animals. Control animals did not show changes in sleep after sham
      infection with allantoic fluid. The H1N1 virus also caused dramatic decreases in
      body temperature and locomotor activities with a latency about 4-5 hr after viral
      inoculation. The H3N2 virus induced very similar changes in sleep, although the
      effects were much smaller in magnitude than those induced by the H1N1 virus, even
      though a much higher dose (10-fold) of the H3N2 virus was used. The present study
      shows that influenza viral infection induces profound and long-lasting increase
      of NREMS and suppression of REMS. These viral-induced changes in sleep likely
      represent a host-defense response.

PMID- 8539263
TI  - Biliary lithocholate and cholestasis during and after total parenteral nutrition:
      an experimental study.
AB  - To evaluate the role of lithocholic acid (LCA) in the etiology of parenteral
      nutrition-associated cholestasis (PN-AC), we studied (i) the changes in the
      percentage of biliary LCA and (ii) the emergence and resolution of cholestatic
      changes in the liver after total parenteral nutrition (TPN) and after 6 weeks of
      oral feeding following the TPN. We compared these changes in rabbits on TPN
      support (via a central vein) for 14 days (TPN, n = 8) with those after 6 weeks of
      refeeding (Post-TPN, n = 8). Age-matched rabbits on lab chow served as controls
      (CHOW, n = 8). At the end of the diet regimens, the common bile duct was
      cannulated under anesthesia, and hepatic bile collected for measurements of bile
      flow and bile acid (BA) secretion rates, and BA profiles. The 60-min biliary
      excretion of sulfobromophthalein (BSP) after an intravenous bolus (5 mg/kg) was
      determined. A liver biopsy was taken for light microscopy. After 14 days of TPN,
      bile flow was reduced by 60%, bile acid secretion by 52%, and BSP excretion by
      38%. On refeeding, only the BSP excretory rate recovered fully. In the TPN group,
      histology of the liver showed hepatocellular degeneration and portal tract
      inflammation; these resolved after refeeding leaving a mild portal fibrosis in
      4/8 rabbits. Total colonic stasis occurred during TPN. With TPN, a decrease in
      the percentage of biliary glycochenodeoxycholate and an increase in LCA% were
      seen, whereas after refeeding the increase was in the percentage of
      glycoursodeoxycholate. An LCA% > or = 6 was associated with liver cell damage.
      After 6 weeks of refeeding, the structural cholestasis disappeared, but the
      decreases in basal bile flow and bile acid secretion (functional cholestasis)
      persisted. These data associate an increase in biliary LCA with the emergence of
      cholestasis during TPN in rabbits.

PMID- 8539264
TI  - Altered tissue amino acid metabolism in acute T-2 toxicosis.
AB  - T-2 toxin is a Fusarium trichothecene mycotoxin that has been shown to alter
      brain neurochemistry and eating behavior in animals eating contaminated diets.
      Experiments were conducted to determine the role of altered tissue amino acid
      metabolism in the etiology of acute T-2 toxicosis. Fasted weanling rats were
      orally dosed with 0 or 2.0 mg T-2 toxin/kg body weight. Blood, brain, liver, and
      muscle tissue were excised 4 and 8 hr after dosing, and amino acid concentrations
      were determined. Hepatic enlargement coupled with reduced liver concentrations of
      free small neutral, large neutral, and basic amino acids were seen 4 hr after
      dosing. Brain and muscle amino acid concentrations were largely refractory to
      treatment, while the plasma concentrations of tyrosine and lysine, and the sum of
      the basic amino acids fell. Hepatic amino acid concentrations returned to control
      levels 8 hr after dosing at which time aminoacidemia was seen. This was due
      partially to an increase in plasma concentrations of large neutral amino acids
      including particularly the branched-chain amino acids. A subsequent experiment
      was conducted to determine the effect of T-2 toxin on 14C-leucine uptake and
      incorporation into protein in liver slices 4 hr after dosing. Exposure to T-2
      toxin reduced total (free + protein-bound) uptake of leucine due primarily to
      reduced incorporation of leucine into newly-synthesized hepatic protein. It was
      concluded that reduced amino acid uptake by liver preceded aminoacidemia in acute
      T-2 toxicosis, although it is not clear how this might influence subsequent
      changes in brain neurochemistry and behavior.

PMID- 8539265
TI  - Early genes induction in spontaneously hypertensive rats left ventricle with
      angiotensin-converting enzyme inhibitors but not hydralazine.
AB  - Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE)
      inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr.
      To examine whether administration of antihypertensive agents affects expression
      of immediate early genes in left ventricular myocardium, groups of rats were
      sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left
      ventricular tissue and analyzed by blot hybridization technique using labeled
      probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents
      reduced pressure similarly, and treatment with the two ACE inhibitors increased c
      fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did
      not increase steady-state mRNA expression of either proto-oncogene. Thus, in
      parallel with the pressure fall, acute administration of the ACE inhibitors
      induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the
      equidepressor dose of hydralazine did not affect expression of these proto
      oncogenes, this effect of ACE inhibitors is independent of their hemodynamic
      action.

PMID- 8539266
TI  - Use of stable isotopic selenium as a tracer to follow incorporation of selenium
      into selenoproteins.
AB  - Stable isotopes of selenium (Se) have been used in human studies to measure Se
      absorption, retention and excretion. The purpose of this study was to examine
      whether stable Se could also be used to follow the incorporation of Se into
      selenoproteins and whether selenoproteins are labeled with stable isotopes the
      same way they are with radioactive Se. Rats fed either a Se-deficient or a high
      Se diet were injected with either a radioactive (75Se) or a stable isotope of Se
      (77Se), and the liver cytosol was chromatographed on Sephadex G-200. Compared
      with 75Se, a greater percentage of 77Se was incorporated into cytosol, but the
      distribution and the effect of dietary Se was similar for both isotopes. New
      Zealand long-eared rabbits were also injected with either 77Se or 75Se, and the
      plasma was chromatographed. More of the 75Se was incorporated into the plasma,
      but again the patterns of incorporation were similar for both isotopes. Plasma
      from a male subject who ingested 60 micrograms of 77Se was chromatographed, and
      the stable Se was detected in column fractions and showed a distribution similar
      to that observed for rabbit plasma. Finally, a polyacrylamide gel electrophoresis
      (PAGE) method was developed that allowed loading of sufficient protein to analyze
      for 77Se in individual protein fractions. The distribution of 77Se and 75Se in
      rabbit plasma was similar. Human plasma was electrophoresed by a similar method
      and peaks of 56 and 23 kDa were detected. These data show that stable isotopes of
      Se can be used for selenoprotein production in the same way as radioactive
      isotopes. They also show that, when physiological amounts of stable Se are
      ingested by humans, the isotope can be detected in blood-borne proteins separated
      by column chromatography and PAGE.

PMID- 8539267
TI  - A protein less sensitive to trypsin, guanidinated casein, is a potent stimulator
      of exocrine pancreas in rats.
AB  - Previously, we have shown that, in rats that have had bile-pancreatic juice (BPJ)
      diverted from the proximal small intestine for 7 days, the exocrine pancreatic
      secretion was enhanced after they were fed a casein, fat-free diet. This
      demonstrates that the pancreatic secretion is stimulated by dietary protein with
      a pancreatic protease-independent pathway. To examine the chemical structure of
      casein responsible for the enhancement of pancreatic secretion, we prepared
      chemically modified casein in which lysine residues were guanidinated. Secretion
      of protein, amylase, and chymotrypsin in the chronic BPJ-diverted rat was
      increased much more after the rats were fed a diet containing guanidinated casein
      (250 g/kg diet) than after they were fed a diet containing intact casein (250
      g/kg diet). In normal rats whose diverted BPJ was returned to the duodenum, the
      increases in the pancreatic secretion after consuming the guanidinated casein
      diet were comparable to those after consuming the intact casein diet. In vitro
      digestibility of guanidinated casein by trypsin and chymotrypsin was much lower
      than that of intact casein. Also, guanidinated casein inhibited tryptic
      hydrolysis of benzoyl-L-arginine p-nitroanilide to a lesser extent than did
      intact casein as determined by an in vitro assay. These results demonstrate that
      guanidinated casein is less sensitive to trypsin than is intact casein and that
      the structure that is sensitive to trypsin is not involved in the stimulation of
      pancreatic secretion in diverted rats. The results evidence that masking luminal
      trypsin activity does not predominantly contribute to the enhancement of
      pancreatic secretion in 7-day BPJ-diverted rats. Also, in normal rats, the
      luminal protease-independent mechanism may play a role partly in increasing the
      pancreatic secretion by dietary protein.

PMID- 8539268
TI  - Pharmacological and physiological significance of ion channels and factors that
      modulate them in vascular tissues.

PMID- 8539269
TI  - Pulmonary edema.

PMID- 8539270
TI  - Evolution of undergraduate education in ambulatory settings: historical models.

PMID- 8539271
TI  - The metaphysics of holism: laughter in carnival with alternative medicine.

PMID- 8539272
TI  - Academic medical research: will collaboration with industry and national
      laboratories save it?

PMID- 8539274
TI  - An overview of medical education in Italy.

PMID- 8539273
TI  - The language of acupuncture: should Western physicians learn it?

PMID- 8539275
TI  - Vincent van Gogh's birthday.

PMID- 8539276
TI  - The essentiality of biomedical research.

PMID- 8539277
TI  - After the generalist, what?

PMID- 8539279
TI  - A reason to choose medicine.

PMID- 8539278
TI  - Lessons to be learned.

PMID- 8539280
TI  - The morality of using antidepressants.

PMID- 8539281
TI  - Did George III have porphyria?

PMID- 8539282
TI  - William James and vivisection.

PMID- 8539283
TI  - Coming together during World War I: medicine's response to the challenges of
      trench warfare.

PMID- 8539284
TI  - Annexins of plant cells.

PMID- 8539285
TI  - Phytochelatins and related peptides. Structure, biosynthesis, and function.

PMID- 8539286
TI  - Arabidopsis mutants lacking phenolic sunscreens exhibit enhanced ultraviolet-B
      injury and oxidative damage.
AB  - We have assessed ultraviolet-B (UV-B)-induced injury in wild-type Arabidopsis
      thaliana and two mutants with altered aromatic secondary product biosynthesis.
      Arabidopsis mutants defective in the ability to synthesize UV-B-absorbing
      compounds (flavonoids in transparent testa 5 [tt5] and sinapate esters in ferulic
      acid hydroxylase 1 [fah1]) are more sensitive to UV-B than is the wild-type
      Landsberg erecta. Despite its ability to accumulate UV-absorptive flavonoid
      compounds, the ferulic acid hydroxylase mutant fah1 exhibits more physiological
      injury (growth inhibition and foliar lesions) than either wild type or tt5. The
      extreme UV-B sensitivity of fah1 demonstrates the importance of hydroxycinnamate
      esters as UV-B protectants. Consistent with the whole-plant response, the highest
      levels of lipid and protein oxidation products were seen in fah1. Ascorbate
      peroxidase enzyme activity was also increased in the leaves of UV-B-treated
      plants in a dose- and genotype-dependent manner. These results demonstrate that,
      in A. thaliana, hydroxycinnamates are more effective UV-B protectants than
      flavonoids. The data also indicate that A. thaliana responds to UV-B as an
      oxidative stress, and sunscreen compounds reduce the oxidative damage caused by
      UV-B.

PMID- 8539287
TI  - Induction of nopaline synthase promoter activity by H2O2 has no direct
      correlation with salicylic acid.
AB  - Transgenic tobacco (Nicotiana tabacum L.) plants carrying a fusion between the
      nopaline synthase (nos) promoter and chloramphenicol acetyltransferase (CAT)
      reporter gene (caf) were tested for their response to treatment with H2O2. The
      nos promoter-driven CAT activity increased significantly by addition of H2O2,
      reaching the maximum level at 15 mM. Kinetic analysis for CAT activity showed
      that induction by H2O2 was similar to that of methyl jasmonate (MJ), but was much
      slower than induction by salicylic acid (SA). Time-course experiments for mRNA
      level also revealed that the response to H2O2 treatment was similar to that of
      MJ. The nos promoter displayed a rapid and transient induction of mRNA with SA
      treatment, with the maximum levels occurring at 3 h, whereas the levels induced
      by H2O2 or MJ treatment increased continuously during the 11-h experimental
      period. The antioxidants N-acetyl-L-cysteine and catechol did not alter the SA
      effect. The responses of the nos promoter to H2O2, MJ, and wounding were
      significantly reduced by deletions of the CAAT box region and the sequence
      between -112 and -101. However, these deletions did not significantly alter the
      SA response. This suggests that H2O2 may have a different mechanism from that of
      SA for inducing nos promotor activity.

PMID- 8539288
TI  - Stable accumulation of Aspergillus niger phytase in transgenic tobacco leaves.
AB  - Phytase from Aspergillus niger increases the availability of phosphorus from feed
      for monogastric animals by releasing phosphate from the substrate phytic acid. A
      phytase cDNA was constitutively expressed in transgenic tobacco (Nicotiana
      tabacum) plants. Secretion of the protein to the extracellular fluid was
      established by use of the signal sequence from the tobacco pathogen-related
      protein S. The specific phytase activity in isolated extracellular fluid was
      found to be approximately 90-fold higher than in total leaf extract, showing that
      the enzyme was secreted. This was confirmed by use of immunolocalization. Despite
      differences in glycosylation, specific activities of tobacco and Aspergillus
      phytase were identical. Phytase was found to be biologically active and to
      accumulate in leaves up to 14.4% of total soluble protein during plant
      maturation. Comparison of phytase accumulation and relative mRNA levels showed
      that phytase stably accumulated in transgenic leaves during plant growth.

PMID- 8539289
TI  - Seed and 4-chloroindole-3-acetic acid regulation of gibberellin metabolism in pea
      pericarp.
AB  - In this study, we investigated seed and auxin regulation of gibberellin (GA)
      biosynthesis in pea (Pisum sativum L.) pericarp tissue in situ, specifically the
      conversion of [14C]GA19 to [14C]GA20. [14C]GA19 metabolism was monitored in
      pericarp with seeds, deseeded pericarp, and deseeded pericarp treated with 4
      chloroindole-3-acetic acid (4-CI-IAA). Pericarp with seeds and deseeded pericarp
      treated with 4-CI-IAA continued to convert [14C]GA19 to [14C]GA20 throughout the
      incubation period (2-24 h). However, seed removal resulted in minimal or no
      accumulation of [14C]GA20 in pericarp tissue. [14C]GA29 was also identified as a
      product of [14C]GA19 metabolism in pea pericarp. The ratio of [14C]GA29 to
      [14C]GA20 was significantly higher in deseeded pericarp (with or without
      exogenous 4-CI-IAA) than in pericarp with seeds. Therefore, conversion of
      [14C]GA20 to [14C]GA29 may also be seed regulated in pea fruit. These data
      support the hypothesis that the conversion of GA19 to GA20 in pea pericarp is
      seed regulated and that the auxin 4-CI-IAA can substitute for the seeds in the
      stimulation of pericarp growth and the conversion of GA19 to GA20.

PMID- 8539290
TI  - Effect of volatile methyl jasmonate on the oxylipin pathway in tobacco, cucumber,
      and arabidopsis.
AB  - The effect of atmospheric methyl jasmonate on the oxylipin pathway was
      investigated in leaves of tobacco (Nicotiana tabacum L.), cucumber (Cucumis
      sativa L.), and Arabidopsis thaliana (L.). Differential sensitivities of test
      plants to methyl jasmonate were observed. Thus, different concentrations of
      methyl jasmonate were required for induction of changes in the oxylipin pathway.
      Arabidopsis was the least and cucumber the most sensitive to methyl jasmonate.
      Methyl jasmonate induced the accumulation of lipoxygenase protein and a
      corresponding increase in extractable lipoxygenase activity. Atmospheric methyl
      jasmonate additionally induced hydroperoxide lyase activity and the enhanced
      production of several volatile six-carbon products. It is interesting that lipid
      hydroperoxidase activity, which is a measure of hydroperoxide lyase plus allene
      oxide synthase plus possibly other lipid hydroperoxide-metabolizing activities,
      was not changed by methyl jasmonate treatment. Methyl jasmonate selectively
      altered the activity of certain enzymes of the oxylipin pathway (lipoxygenase and
      hydroperoxide lyase) and increased the potential of leaves for greatly enhanced
      six-carbon-volatile production.

PMID- 8539292
TI  - Examination of the contribution of vacuolar proteases to intracellular protein
      degradation in Chara corallina.
AB  - The contribution of proteases in the central vacuole of Chara corallina
      internodal cells to overall cellular protein degradation was examined. I measured
      the decrease in the trichloroacetic acid (TCA)-precipitable radioactivity in the
      cell for a 6-d chase period after labeling cellular proteins with [3H]leucine.
      The kinetics of [3H]leucine-labeled protein disappearance showed that the half
      life of the cellular soluble proteins was 4 to 5 d. This value did not change
      when cells were treated with (2S,3S)-trans-epoxysuccinyl-L-leucylamido- 3-methyl
      butane ethyl ester, a permeant inhibitor of cysteine proteases. This inhibitor
      mostly inhibited bovine serum albumin-degrading activity in the vacuole. I also
      measured the release of TCA-soluble radioactivity from the TCA-insoluble fraction
      in the cell. This experiment showed that 13% of [3H]leucine-labeled cellular
      proteins were degraded in 1 d. This value agreed well with the half-life obtained
      for soluble proteins in the above experiment. This value did not change even when
      both trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, a cysteine protease
      inhibitor, and pepstatin A, an aspartic protease inhibitor, were introduced into
      the vacuole. With this operation, bovine serum albumin-degrading activity in the
      vacuole was almost completely inhibited. These data suggest that the cytoplasmic
      but not the vacuolar proteases contribute to cellular protein turnover in Chara
      internodal cells.

PMID- 8539291
TI  - Light-harvesting chlorophyll a/b-binding protein inserted into isolated
      thylakoids binds pigments and is assembled into trimeric light-harvesting
      complex.
AB  - The light-harvesting chlorophyll a/b-binding protein (LHCP) is largely protected
      against protease (except for about 1 kD on the N terminus) in the thylakoid
      membrane; this protease resistance is often used to assay successful insertion of
      LHCP into isolated thylakoids in vitro. In this paper we show that this protease
      resistance is exhibited by trimeric light-harvesting complex of photosystem II
      (LHCII) but not by monomeric LHCII in which about 5 kD on the N terminus of LHCP
      are cleaved off by protease. When a mutant version of LHCP that is unable to
      trimerize in an in vitro reconstitution assay is inserted into isolated
      thylakoids, it gives rise to only the shorter protease digestion product
      indicative of monomeric LHCII. We conclude that more of the N-terminal domain of
      LHCP is shielded in trimeric than in monomeric LHCII and that this difference in
      protease sensitivity can be used to distinguish between LHCP assembled in LHCII
      monomers or trimers. The data presented prove that upon insertion of LHCP into
      isolated thylakoids at least part of the protein spontaneously binds pigments to
      form LHCII, which then is assembled in trimers. The dependence of the protease
      sensitivity of thylakoid-inserted LHCP on the oligomerization state of the newly
      formed LHCII justifies caution when using a protease assay to verify successful
      insertion of LHCP into the membrane.

PMID- 8539293
TI  - Molecular characterization of the plastidic glucose-6-phosphate dehydrogenase
      from potato in comparison to its cytosolic counterpart.
AB  - We report on the cloning of a plastidic glucose-6-phosphate dehydrogenase (EC
      1.1.1.49) from higher plants. The complete sequence of the plastidic enzyme was
      obtained after rapid amplification of cDNA ends and comprises a putative
      plastidic transit peptide. Sequences amplified from leaf or root poly(A+) RNA are
      identical. In contrast to the cytosolic enzyme, the plastidic isoform is subject
      to redox modulation, i.e. thioredoxin-mediated inactivation by light. But when
      the plastidic enzyme is compared to a cyanobacterial homolog, none of the
      cysteine residues is conserved. The recombinant enzyme was used to raise
      antibodies in rabbits. Gene expression was studied in potato (Solanum tuberosum
      L.), at both the RNA and protein levels, revealing different patterns for the
      isoforms. The gene encoding the cytosolic enzyme was transcribed in all tissues
      tested, and the highest transcription was detected in tubers. In contrast,
      expression of the gene encoding the plastidic enzyme was confined to green
      tissues. Wounding of leaves resulted in a slight increase in the expression of
      the gene encoding the cytosolic isoform and a shutdown of the plastidic
      counterpart. Compared to the situation in soil, elevated transcription of the
      gene encoding the plastidic enzyme is found in roots of hydroponically grown
      potato plants, which is in agreement with the postulated role for this isoform in
      nitrite reduction.

PMID- 8539294
TI  - Lupinus albus L. pathogenesis-related proteins that show similarity to PR-10
      proteins.
AB  - We describe a group of three acidic proteins, pathogenesis-related (PR)-p16.5a,
      PR-p16.5b, and PR-p16.5c, that accumulate in the leaves of Lupinus albus L. cv
      Rio Maior plants when infected with the fungus Colletotrichum gloeosporioides
      Penz. These proteins co-migrate in sodium dodecyl sulfate-polyacrylamide gels as
      a single band of 16.5 kD, behaving as charge isomers, and are related to several
      members of the defense-related PR-10 protein family. Localization of the proteins
      was investigated by techniques of tissue printing and immunogold electron
      microscopy; they are predominantly associated with the vascular system and are
      localized extracellularly. The accumulation of PR-p16.5a, PR-p16.5b, and PR
      p16.5c also seems to be induced by cucumber mosaic virus and by two forms of
      abiotic stress, salicylic acid and ultraviolet, suggesting a general defense role
      for these proteins.

PMID- 8539295
TI  - Structural requirements of oleosin domains for subcellular targeting to the oil
      body.
AB  - We have investigated the protein domains responsible for the correct subcellular
      targeting of plant seed oleosins. We have attempted to study this targeting in
      vivo using "tagged" oleosins in transgenic plants. Different constructs were
      prepared lacking gene sequences encoding one of three structural domains of
      natural oleosins. Each was fused in frame to the Escherichia coli uid A gene
      encoding beta-glucuronidase (GUS). These constructs were introduced into Brassica
      napus using Agrobacterium-mediated transformation. GUS activity was measured in
      washed oil bodies and in the soluble protein fraction of the transgenic seeds. It
      was found that complete Arabidopsis oleosin-GUS fusions undergo correct
      subcellular targeting in transgenic Brassica seeds. Removal of the C-terminal
      domain of the Arabidopsis oleosin comprising the last 48 amino acids had no
      effect on overall subcellular targeting. In contrast, loss of the first 47 amino
      acids (N terminus) or amino acids 48 to 113 (which make up a lipophilic core)
      resulted in impaired targeting of the fusion protein to the oil bodies and
      greatly reduced accumulation of the fusion protein. Northern blotting revealed
      that this reduction is not due to differences in mRNA accumulation. Results from
      these measurements indicated that both the N-terminal and central oleosin domain
      are important for targeting to the oil body and show that there is a direct
      correlation between the inability to target to the oil body and protein
      stability.

PMID- 8539296
TI  - Isolation of a polyubiquitin promoter and its expression in transgenic potato
      plants.
AB  - A polyubiquitin clone (ubi7) was isolated from a potato (Solanum tuberosum)
      genomic library using a copy-specific probe from a stress-induced ubiquitin cDNA.
      The genomic clone contained a 569-bp intron immediately 5' to the initiation
      codon for the first ubiquitin-coding unit. Two chimeric beta-glucuronidase (GUS)
      fusion transgenes were introduced into potato. The first contained GUS fused to a
      1156-bp promoter fragment containing only 5' flanking and 5' untranslated
      sequences from ubi7. The second transgene contained GUS translationally fused to
      the carboxy terminus of the first ubiquitin-coding unit and thus included the
      intron present in the 5' untranslated region of the polyubiquitin gene. Both ubi7
      GUS transgenes were activated by wounding in tuber tissue and in leaves by
      application of exogenous methyl jasmonate. They were also expressed
      constitutively in the potato tuber peel (outer 1-2 mm). Both transgenes were
      actively expressed in mature leaves. Exceptionally high levels of expression were
      observed in senescent leaves. Transgenic clones containing the ubi7 intron and
      the first ubiquitin-coding unit showed GUS expression levels at least 10 times
      higher than clones containing GUS fused to the intronless promoter.

PMID- 8539297
TI  - Molecular dissection of the epsilon subunit of the chloroplast ATP synthase of
      spinach.
AB  - The gene encoding the epsilon subunit (atpE) of the chloroplast ATP synthase of
      Spinacia oleracea has been overexpressed in Escherichia coli. The recombinant
      protein can be solubilized in 8 M urea and directly diluted into buffer
      containing ethanol and glycerol to obtain epsilon that is as biologically active
      as epsilon purified from chloroplast-coupling factor 1 (CF1). Recombinant epsilon
      folded in this manner inhibits the ATPase activity of soluble and membrane-bound
      CF1 deficient in epsilon and restores proton impermeability to thylakoid
      membranes reconstituted with CF1 deficient in epsilon. Site-directed mutagenesis
      was used to generate truncations and single amino acid substitutions in the
      primary structure of epsilon. In the five mutants tested, alterations that weaken
      ATPase inhibition by recombinant epsilon affect its ability to restore proton
      impermeability to a similar extent, with one exception. Substitution of histidine
      37 with arginine appears to uncouple ATPase inhibition and the restoration of
      proton impermeability. As in the case of E. coli, it appears that N-terminal
      truncations of the epsilon subunit have more profound effects than C-terminal
      deletions on the function of epsilon. Recombinant epsilon with six amino acids
      deleted from the C terminus, which is the only region of significant mismatch
      between the epsilon of spinach and the epsilon of Pisum sativum, inhibits ATPase
      activity with a reduced potency similar to that of purified pea epsilon. Four of
      the six amino acids are serine or threonine. These hydroxylated amino acids may
      be important in epsilon-CF1 interactions.

PMID- 8539298
TI  - Lysophosphatidic acid acyltransferase from meadowfoam mediates insertion of
      erucic acid at the sn-2 position of triacylglycerol in transgenic rapeseed oil.
AB  - Lysophosphatidic acid acyltransferase acylates the sn-2 hydroxyl group of
      lysophosphatidic acid to form phosphatidic acid, a precursor to triacylglycerol.
      A cDNA encoding lysophosphatidic acid acyltransferase was isolated from
      developing seeds of meadowfoam (Limnanthes alba alba). The cDNA encodes a 281
      amino acid protein with a molecular mass of 32 kD. The cDNA was expressed in
      developing seeds of transgenic high-erucic-acid rapeseed (Brassica napus) using a
      napin expression cassette. Erucic acid was present at the sn-2 position of
      triacylglycerols from transgenic plants but was absent from that position of seed
      oil extracted from control plants. Trierucin was present in the transgenic oil.
      Alteration of the sn-2 erucic acid composition did not affect the total erucic
      acid content. These experiments demonstrate the feasibility of using
      acyltransferases to alter the stereochemical composition of transgenic seed oils
      and also represent a necessary step toward increasing the erucic acid content of
      rapeseed oil.

PMID- 8539300
TI  - The electronic Plant Gene Register.

PMID- 8539299
TI  - Differential induction of cytochrome P450-mediated triasulfuron metabolism by
      naphthalic anhydride and triasulfuron.
AB  - Cytochrome P450 monooxygenases play paramount roles in the detoxification of
      herbicides as well as in the synthesis of lignins, flavonoids, and phenolic
      acids. Biochemical analysis of triasulfuron metabolism in maize (Zea mays)
      seedlings has demonstrated that the P450(s) responsible for detoxification of
      this herbicide is induced by naphthalic anhydride (NA), a plant safener, and by
      triasulfuron, the herbicide itself. Induction studies conducted with seedlings of
      different ages suggest that two separate response pathways modulate this P-450
      activity. Induction by NA is independent of the developmental age of the
      seedlings up to 6.5 d; induction by triasulfuron is tightly modulated with
      respect to developmental age in that triasulfuron metabolism can be induced by
      triasulfuron in young (2.5 d) but not older (6.5 d) seedlings. Induction by NA
      administered in combination with triasulfuron synergistically enhances
      triasulfuron metabolism in younger seedlings to levels substantially above that
      obtained with either herbicide or safener treatment alone. In older seedlings, NA
      plus triasulfuron treatment induces triasulfuron metabolism to only the level of
      NA treatment alone, indicating again that the induction cascade responding to
      triasulfuron is nonfunctional in later development. MnCl2 studies indicate that
      the triasulfuron insensitivity of older seedlings does not result from a general
      limitation in the inducibility of this P-450 detoxification system but rather
      from specific limitations in the triasulfuron-response pathway.

PMID- 8539301
TI  - Autobiographical memory for childhood events: patterns of recall in psychiatric
      patients with a history of alleged trauma.
AB  - Social scientists are currently being pressed upon by the legal and scientific
      communities to provide more definitive explanations regarding the nature and
      functions of memory (Loftus 1993). At the forefront of this debate is
      autobiographical memory. Autobiographical memory is a subclassification of memory
      within the declarative memory system and signifies memory for one's own personal
      life experiences in the recent and/or remote past. This study investigates the
      relationship between early trauma and memory for childhood events in adult
      psychiatric patients. The findings suggest that patients with an alleged history
      of trauma have a measurably different pattern of recall for early events than the
      patient and nonpatient comparison groups.

PMID- 8539302
TI  - The neurosociology of schizophrenia: vulnerability and functional disability.
AB  - It has been maintained that becoming a schizophrenic is essentially "a social and
      interpersonal process, not an inevitable consequence of primary symptoms and
      neurochemical abnormality" (Estroff 1989). It is the intent of this paper to
      elaborate on this theme by exploring how the neuropsychological deficits of
      schizophrenia relate to the observed social handicaps of people who carry the
      diagnosis. We argue that a better understanding of schizophrenia requires inquiry
      into the handicaps as well as the process whereby schizophrenic and
      preschizophrenic men and women try and fail to negotiate socially mandated roles.
      Of necessity, such an inquiry will require mixing levels of explanation (Meehl
      1990) and will draw upon insights from the disciplines of psychiatry,
      neuropsychology, and sociology.

PMID- 8539303
TI  - Four encounters between descendants of survivors and descendants of perpetrators
      of the Holocaust: building social bonds out of silence.

PMID- 8539304
TI  - Narrative constructions of historical realities in testimony with Bosnian
      survivors of "ethnic cleansing".
AB  - Mental health care for traumatized refugees includes practices common to
      mainstream mental health care but also modifications and innovations in technique
      and approach. One such innovation, the testimony method, was first described by a
      group of Chilean psychiatrists working with Chilean survivors of torture from
      political repression (Cienfuego and Monelli 1983). The testimony method has been
      used as a time-limited psychotherapeutic intervention, often within the context
      of an extended, supportive psychotherapy. This method consists of asking
      individuals to tell in detail the story of their experiences of victimization
      from state-sponsored violence and recording their narrative accounts verbatim.
      Agger and Jensen's account of this method depicts testimony as a universal
      practice, appearing in multiple cultures and at different points in history
      (Agger and Jensen 1990). They also note that testimony simultaneously functions
      in both the private and public domains; and as confession embodying the person's
      spiritual, ethical, aesthetic, and philosophical values, and as evidence
      documenting the occurrence of evil events to the world.

PMID- 8539305
TI  - Interviewing Eddie.

PMID- 8539306
TI  - Truths that cannot go naked: shame in many forms.

PMID- 8539307
TI  - Sex differences in depression: a role for preexisting anxiety.
AB  - The role of anxiety disorders in the development of sex differences in major
      depression is analyzed. Data come from a longitudinal epidemiologic study of
      young adults in the Detroit, Michigan area. The Diagnostic Interview Schedule,
      revised according to DSM-III-R, was used at baseline to measure lifetime
      psychiatric disorders and at follow-up to measure psychiatric disorders during
      the 3.5-year interval since baseline assessment. Consistent with previous
      reports, the lifetime prevalence of major depression was nearly two-fold higher
      in females than in males. The sex difference was primarily in major depression
      comorbid with anxiety disorders. Results from Cox-proportional hazards models,
      with time-dependent covariates, showed that prior anxiety disorder increased the
      risk for subsequent major depression in both sexes, with no evidence of an
      interaction. History of anxiety disorder, including number of prior anxiety
      disorders, accounted for a considerable part of the observed sex difference in
      major depression. Controlling for prior anxiety reduced by more than 50% the
      coefficient that estimates the association between gender and major depression.
      The results suggest that the higher occurrence of anxiety disorders in females
      than males beginning early in life might explain in large part the higher female
      risk for major depression. They emphasize the need for further research on sex
      differences in anxiety disorders.

PMID- 8539308
TI  - Comparing the cost effectiveness of psychiatric treatments: bulimia nervosa.
AB  - We conducted an exploratory post hoc study that compared the cost effectiveness
      of five treatments for bulimia nervosa: 15 weeks of cognitive behavioral therapy
      (CB) followed by three monthly sessions, 16 weeks (Med16) and 24 weeks (Med24) of
      desipramine (< or = 300 mg/day), and CB combined with desipramine for those
      durations (Combo16 and Combo24). We illustrate how a treatment's cost
      effectiveness varies according to when evaluation is done and how effectiveness
      and cost are defined. At 32 weeks, Med16 appears the most cost-effective
      treatment, and Combo16 appears the least. At 1 year, Med24 appears the most cost
      effective treatment, and Combo16 appears the least. Using this post hoc analysis
      as an example, we discuss the pitfalls and limitations of cost-effectiveness
      analysis of psychiatric treatments.

PMID- 8539309
TI  - Time course of the corticosteroid-dopaminergic interaction during metyrapone and
      dexamethasone administration.
AB  - Recent studies performed with depressed patients and normal subjects suggest that
      corticosteroids may alter dopaminergic activity. We measured the time course of
      the interaction between corticosteroid and plasma homovanillic acid (HVA) levels
      in 10 young healthy subjects after the administration of 2 mg of dexamethasone in
      session 1 and after the administration of 4.5 g of metyrapone in session 2.
      Plasma levels of adrenocorticotropic hormone (ACTH), 11-desoxycortisol, cortisol,
      HVA, and prolactin (PRL) were measured at 08:00, 09:00, 12:00, 15:00, and 16:00 h
      on a baseline day and during both drug-administration sessions. Dexamethasone
      administration resulted in a significant decrease in plasma levels of ACTH, 11
      desoxycortisol, and cortisol at all time points and to a significant decrease in
      PRL secretion in the early morning. Plasma HVA levels were unchanged after
      dexamethasone administration. Metyrapone administration resulted in a significant
      decrease in cortisol levels and a significant increase in ACTH and 11
      desoxycortisol levels. Plasma HVA levels were significantly increased in the
      early morning, while PRL levels were unaltered. These results are discussed in
      relation to the neurochemical and behavioral changes associated with steroid
      administration and interpreted with regard to a possible association between HVA
      and PRL in the effects of corticosteroids on dopaminergic activity.

PMID- 8539310
TI  - Wisconsin Card Sorting Test performance in obsessive-compulsive disorder: no
      evidence for involvement of dorsolateral prefrontal cortex.
AB  - Wisconsin Card Sorting Test (WCST) performances were studied in 33 patients with
      obsessive-compulsive disorder (OCD) and 33 age-, sex-, and education-matched
      normal comparison subjects; the OCD patients were divided into four subgroups on
      the basis of their symptomatology. Neither the two groups of subjects nor the
      four OCD subgroups differed on any of the WCST neuropsychological indices. No
      relationship was demonstrated between test performance and clinical
      epidemiological characteristics of the OCD patients. All of the OCD patients were
      being treated with fluvoxamine maleate, which improves OCD symptoms and could
      also improve WCST performances. Nevertheless, no remarkable differences in the
      WCST indices were observed in patients treated with fluvoxamine when compared
      with patients who had not received a specific therapy for at least 3 weeks. Since
      the WCST is widely considered sensitive to dysfunction of the dorsolateral
      prefrontal cortex, our results do not support the involvement of that brain
      region in OCD.

PMID- 8539311
TI  - Schizophrenic syndrome and Wisconsin Card Sorting Test dimensions.
AB  - A principal component analysis of Wisconsin Card Sorting Test (WCST) scores has
      recently shown three factors. Only the Perseveration factor may measure the
      activity of the dorsolateral prefrontal cortex in schizophrenic patients. Liddle
      has hypothesized that a dysfunction in this area is specifically related to the
      negative syndrome and not to other schizophrenic syndromes (positive and
      disorganization). The factor analysis of the WCST was replicated with similar
      results in 38 schizophrenic or schizoaffective patients. In the total group, the
      correlation between the negative syndrome and the Perseveration factor did not
      reach significant levels. In the patients with a DSM-III-R diagnosis of
      schizophrenia (n = 30), the correlations did reach significant levels.

PMID- 8539312
TI  - Abnormal smooth pursuit eye movements in schizophrenic patients are associated
      with cerebral glucose metabolism in oculomotor regions.
AB  - The purpose of this study was to test the hypothesis that abnormal smooth pursuit
      eye movements in schizophrenic patients would be related to cerebral glucose
      utilization in specific oculomotor regions. Eye movements were assessed with
      infrared oculography in 11 unmedicated schizophrenic patients and 13 normal
      comparison subjects. For the patients only, regional cerebral metabolic rate of
      glucose utilization was measured with positron emission tomography. Abnormal
      pursuit tracking in the patients was associated with relatively decreased
      metabolism in the frontal eye fields and increased metabolism in the caudate
      nuclei. The results are consistent with the hypothesis that these cerebral
      regions are involved in the pathophysiology of abnormal pursuit as related parts
      of a cortical-subcortical oculomotor circuit.

PMID- 8539313
TI  - Numbers of preceding nontargets differentially affect responses to targets in
      normal volunteers and patients with schizophrenia: a study of event-related
      potentials.
AB  - This event-related potential study systematically varied the number of nontargets
      (1, 3, 5, 7, 9) preceding the target tone in an oddball experiment and examined
      the effect of this on N2, P3, and reaction time measures in schizophrenic
      patients and normal volunteers. Schizophrenic patients were found to have reduced
      P3 amplitudes, but this reduction was restricted to series when the targets
      followed an intermediate number (3-7) of nontargets, and not when targets
      followed a short (1) or long series (9) of nontargets. Although other
      interpretations of this finding are possible, the pattern of results could be
      explained by the hypothesis that the refractory period governing the generation
      of the P3 component was prolonged in schizophrenia.

PMID- 8539314
TI  - Initial assessment of hospital treatment by patients with paranoid schizophrenia:
      a predictor of outcome.
AB  - The value of schizophrenic inpatients' initial global assessments of treatment in
      the prediction of outcome was investigated. Within 3 days of admission, 31
      patients with an acute paranoid schizophrenic psychosis according to ICD-10 rated
      on a visual analog scale to what extent they believed the treatment they were
      receiving was right for them. Outcome criteria were overall clinical changes
      measured on the Brief Psychiatric Rating Scale and the Intentionality Scale. The
      patients' initial global assessments of treatment were significantly correlated
      to both outcome criteria, indicating that patients with a more positive initial
      assessment of treatment ultimately benefited more than those with a more negative
      appraisal. The predictive correlations were independent of the influence of other
      variables recorded in the study. Patients' initial global assessments should be
      taken seriously in clinical practice and studied systematically in research.

PMID- 8539315
TI  - Screening psychiatric admissions for anticardiolipin antibody.
AB  - Anticardiolipin antibody (aCL) may provide an instrument for screening in
      neuropsychiatric syndromes due to cerebral ischemia. Thirty-five psychiatric
      patients, aCL-positive on admission, were matched against aCL-negative patients.
      Their clinical records on admission and after 2-years of follow-up were analyzed
      without knowledge of aCL results. An inventory was made of cerebrovascular and
      systemic vascular symptoms. In 13 out of 35 aCL-positive cases, vascular
      morbidity, suggesting ischemic causes of central nervous system pathology, could
      be demonstrated during follow-up and none in the comparison group. No correlation
      was found, however, between Hachinski ischemic scores on admission and aCL
      positivity. Yet, if only on the basis of increased incidence of subsequent
      ischemia, the aCL-IgG/M isotype appears to be a valuable predictor of vascular
      neuropsychiatric symptoms.

PMID- 8539316
TI  - Action of intravenously administered talipexole on the rat striatal neurons
      receiving excitatory input from nigral dopamine neurons.
AB  - Electrophysiological studies using rats anesthetized with chloral hydrate were
      performed to elucidate whether or not intravenously injected talipexole acted as
      a D2 receptor agonist on the striatal neurons in comparison with the action of
      bromocriptine. The activities of the striatal neurons were extracellularly
      recorded using a glass microelectrode attached along a seven-barreled
      micropipette, each barrel of which was filled with talipexole, bromocriptine,
      SCH23390 (D1 antagonist), domperidone (D2 antagonist), glutamate or 2 M NaCl.
      These drugs were iontophoretically applied to the immediate vicinity of the
      target neuron being recorded. The effects of talipexole and bromocriptine were
      examined on the neurons, whose spikes (induced by the stimulation of the
      substantia nigra pars compacta) were inhibited by the iontophoretic application
      of domperidone. Iontophoretic application of talipexole or bromocriptine
      increased spontaneous firing of these neurons and this increase in firing was
      also inhibited by iontophoretically applied domperidone. In the same neurons,
      intravenously administered talipexole (0.01, 0.02 and 0.04 mg/kg) dose
      dependently increased firing, and this increase was inhibited by
      microiontophoretically applied domperidone, but not by SCH23390. On the other
      hand, the intravenous injection of bromocriptine (0.1, 0.2 and 0.4 mg/kg) also
      increased the firing rate. However, the increase was not dose-dependent and
      fluctuated; the firing transiently decreased during the increase in firing with
      intravenously administered bromocriptine. However, the bromocriptine-induced
      increase in firing was also suppressed by domperidone, and decrease in firing was
      inhibited by SCH23390. These findings suggest that talipexole acts as a D2
      agonist on the striatal neurons receiving input from substantia nigra pars
      compacta and increases firing when intravenously applied.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8539317
TI  - Post-synaptic 5-HT1A receptor involvement in yawning and penile erections induced
      by apomorphine, physostigmine and mCPP in rats.
AB  - Apomorphine and mCPP induced yawning associated with penile erections in rats,
      whereas physostigmine induced only yawns. Apomorphine-induced yawning and penile
      erections were antagonized by low doses of raclopride, whereas physostigmine
      induced yawning and mCPP-induced effects were only partly inhibited at high doses
      of raclopride. Scopolamine as well as clozapine antagonized yawning and penile
      erections induced by apomorphine, mCPP and physostigmine. Similarly, the 5-HT1A
      agonists 8-OH-DPAT and S 14506 inhibited yawning and penile erections induced by
      apomorphine, mCPP and physostigmine, and at similar doses induced lower lip
      retraction and hyperreactivity to handling. The beta/5-HT1A antagonist tertatolol
      reversed the inhibitory effects of 8-OH-DPAT and S 14506 on drug-induced yawning
      and penile erections and increased apomorphine- and physostigmine-induced yawn
      frequency but not penile erection frequency. Like tertatolol, propranolol
      increased apomorphine- and physostigmine-induced yawn frequency, whereas ICI
      118551 increased only physostigmine-induced yawning. 8-OH-DPAT- and S 14506
      induced lower lip retraction and hyperreactivity to handling were also
      significantly antagonized by tertatolol. Finally, p-chlorophenylalanine
      pretreatment produced about 95% depletion in 5-HT in hypothalamus, hippocampus,
      striatum and frontal cortex and modified neither the responses of the inducing
      drugs nor the inhibitory effects of 8-OH-DPAT and S 14506 on drug-induced yawning
      and penile erections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539318
TI  - Complex stimulus properties of LSD: a drug discrimination study with alpha 2
      adrenoceptor agonists and antagonists.
AB  - The influence of several alpha 2-adrenergic agents on the discriminative stimulus
      (DS) properties of lysergic acid diethylamide (LSD) was studied in rats trained
      to discriminate 0.08 mg/kg (186 nmol/kg) of LSD from saline in a two-lever
      operant paradigm. Only yohimbine fully mimicked LSD with an ED50 of 2.05 mg/kg
      (5.24 mumol/kg). Yohimbine's 5-HT1A agonist properties may be responsible for
      this substitution. Other alpha 2-adrenoceptor antagonists, idazoxan with an
      agonist/antagonist profile at 5-HT1A receptors and RS 26026-197, a highly
      selective alpha 2-adrenoceptor antagonist, failed to produce substitution.
      Clonidine, an alpha 2-adrenoceptor agonist, did not substitute for LSD but the
      response rate was dose-dependently reduced. None of the alpha 2-adrenergic agents
      used for pretreatment before LSD inhibited the response to the LSD training dose.
      Coadministration of clonidine with LSD produced a leftward shift of the dose
      response relationship of LSD without a significant change in the slope of the
      dose-response line. Simultaneous administration of alpha 2-adrenergic agents with
      LSD shifted the dose-response curve to the left only when the adrenergic agent
      also possessed at least moderate affinity for the 5-HT1A receptor. In addition,
      radioligand competition experiments were performed that showed LSD to have
      relatively high affinity (Ki = 37 nM) for [3H]clonidine-labeled sites in rat
      cortex with lower affinity for [3H]yohimbine labeled sites. While previous
      studies have suggested that the nature of the LSD cue may be essentially
      expressed by 5-HT2 receptor activation, the present data show that this cue can
      be modulated by effects of LSD at 5-HT1A and at other monoamine neurotransmitter
      receptors.

PMID- 8539319
TI  - The effects of the kappa agonist U-50,488 on cocaine-induced conditioned and
      unconditioned behaviors and Fos immunoreactivity.
AB  - The ability of kappa opioid agonists to modulate dopamine-mediated behavior and
      Fos immunoreactivity was assessed in adult rats. It was predicted that kappa
      agonist treatment would block the unconditioned and conditioned behaviors
      produced by cocaine (an indirect dopamine agonist). In the initial experiments,
      cocaine-induced locomotor activity was assessed after either acute or chronic
      injections of the kappa receptor agonist U-50,488 (5 mg/kg, SC). As expected, U
      50,488 decreased cocaine-induced activity, while leaving baseline activity levels
      unaffected. Interestingly, chronic treatment with U-50,488 did not induce
      behavioral tolerance. The conditioned effects of cocaine (20 mg/kg, IP) were
      assessed using the conditioned place preference (CPP) paradigm. As expected, rats
      showed a preference for the cocaine-paired compartment, an effect blocked by U
      50,488 (5 mg/kg, SC). One hour after CPP testing, rats were killed and Fos
      immunoreactivity was assessed. Rats conditioned with cocaine, but not U-50,488,
      showed increased Fos activity in the anterior cingulate cortex, piriform cortex,
      lateral septal area, and olfactory tubercles. When considered together, these
      results suggest that U-50,488 was effective at blocking the unconditioned and
      conditioned effects of cocaine, as well as cocaine-induced neuronal activity (as
      measured by Fos induction).

PMID- 8539320
TI  - Opposite role of CCKA and CCKB receptors in the modulation of endogenous
      enkephalin antidepressant-like effects.
AB  - Systemic administration of RB 101, a complete inhibitor of the enkephalin
      degrading enzymes, has been reported to induce naltrindole-reversed
      antidepressant-like effects in the conditioned suppression of motility (CSM) test
      in mice. The selective CCKB antagonist L-365,260 also elicits the same
      naltrindole-blocked responses on CSM. The aim of this study was therefore to
      investigate the possible modulation of RB 101 induced behavioral responses by
      activation or blockade of CCK receptors. Thus, the effects induced by RB 101
      administered alone or associated with an ineffective dose of a selective CCKB
      agonist (BC 264), a CCKB antagonist (L-365,260) or a CCKA antagonist (L-364,718),
      were evaluated on the CSM in mice. RB 101 alone decreased the stress-induced loss
      of motility, as previously reported. The antidepressant-like effect of RB 101 was
      potentiated by L-365,260, and suppressed by BC 264 and to a lesser extent by L
      364,718. The facilitatory effect induced by L-365,260 on RB 101 responses was
      blocked by the delta selective antagonist naltrindole. All these effects occurred
      only in shocked animals. The present results suggest that the activation of CCKA
      and CCKB receptors by endogenous CCK, could play an opposite role in the control
      of behavioral responses induced by endogenous enkephalins. Delta opioid receptors
      seem to be selectively involved in this interaction.

PMID- 8539321
TI  - Ondansetron improves cognitive performance in the Morris water maze spatial
      navigation task.
AB  - In the present studies we investigated the actions of ondansetron, a prototypic 5
      hydroxytryptamine3 (5-HT3) receptor antagonist, on performance in a complex
      spatial navigation/memory task in rats. Specifically, we compared the activity of
      ondansetron to that of the cholinesterase inhibitor physostigmine in attenuating
      two distinct cognitive deficits in the Morris water maze. In the first model,
      rats treated with the muscarinic receptor antagonist atropine (30 mg/kg) had
      significantly longer latencies to find the submerged platform across two days of
      testing. Physostigmine (0.03, 0.1 and 0.3 mg/kg) and ondansetron (0.03-1 mg/kg)
      significantly reduced the latencies to find the submerged platform in atropine
      treated animals, suggesting an increase in cognitive performance. There was
      little evidence of a dose-response relationship for either compound, and a loss
      of efficacy for ondansetron was seen at 3 mg/kg. In the second model, pre
      screened, aged (23 months), cognition-impaired and nonimpaired rats were tested.
      Ondansetron (0.1 mg/kg), but not physostigmine (0.1 mg/kg), decreased the
      latencies to find the submerged platform in the aged-impaired rats, while neither
      compound improved performance of aged-nonimpaired rats. These data suggest that
      ondansetron may have cognition enhancing properties in animal models of aging and
      cholinergic hypofunction.

PMID- 8539322
TI  - Naltrexone, smoking behaviour and cigarette withdrawal.
AB  - In order to examine the role of endogenous opioids in the reinforcing effects of
      nicotine, a double-blind, placebo-controlled, cross-over design was used to study
      the effects of the opiate antagonist, naltrexone, on smoking behaviour and
      cigarette withdrawal in 12 heavy smokers. Although naltrexone (50 mg) appeared to
      reduce the perceived difficulty of abstaining during 24-h cigarette withdrawal,
      other withdrawal symptoms were unaffected. Naltrexone also had no effect on a
      variety of biochemical and behavioural measures of nicotine intake or on
      subjective satisfaction and enjoyment from the first cigarette smoked after 24-h
      abstinence. Similarly naltrexone (100 mg) had no effect on smoking behaviour,
      nicotine intake or satisfaction from smoking during a 48-h period of ad libitum
      smoking. However, during the ad libitum smoking period naltrexone caused mood
      changes of the kind that occur during tobacco withdrawal. Since nicotine intake
      and smoking behaviour were unaffected, the mood changes are unlikely to have been
      mediated by blockade or any other form of opioid interaction with nicotinic
      mechanisms. These findings provide evidence against the notion that the
      endogenous opioids are involved in mediating the reinforcing properties of
      nicotine in smokers under normal conditions.

PMID- 8539323
TI  - Cognitive and EEG recovery following bolus intravenous administration of
      anesthetic agents.
AB  - Bolus intravenous (IV) administration of commonly used IV anesthetic agents such
      as fentanyl and the fentanyl analogues, alfentanil, remifentanil, and sufentanil,
      etomidate and propofol, produced anesthesia in rats as measured by the loss of
      righting (LOR) with calculated ED150 doses of 0.06, 0.09, 0.037, 0.007, 2.51 and
      6.12 mg/kg, respectively. Animals trained in an eight arm radial maze (RAM) were
      assessed for cognitive recovery, as measured by response efficiency (percentage
      of correct arm entries within 10 min), immediately, 15 min and 30 min following
      IV administration of the calculated ED150 dose of each of these agents, and the
      subsequent return of righting (ROR). Animals administered fentanyl or sufentanil
      were unable to successfully complete the maze throughout the testing periods.
      Animals receiving remifentanil showed cognitive recovery within the first testing
      interval (immediately following the return of righting), while animals receiving
      alfentanil, etomidate or propofol showed recovery at the 15-min testing interval
      following ROR. In a separate experiment, bolus IV administration of the ED150
      dose of these agents was evaluated in an acute rat EEG model. Following ROR,
      return to baseline EEG levels occurred at 0.30, 2.88, 5.06, 16.25, 31.29 and
      43.98 min for remifentanil, propofol, alfentanil, etomidate, fentanyl and
      sufentanil, respectively. These data show that the return to efficient cognitive
      functioning corresponds to the return to normal baseline EEG waveforms.

PMID- 8539325
TI  - Lack of involvement of delta-opioid receptors in mediating the rewarding effects
      of cocaine.
AB  - The non-selective opioid antagonist naltrexone and the partial agonist
      buprenorphine have been reported to reduce cocaine self-administration (SA) and
      relapse in both humans and rhesus monkeys. Data suggesting an involvement of
      delta-opioid receptors in modulating the conditioned rewarding effects of cocaine
      were also recently presented. In view of such findings, the present SA and place
      conditioning studies were conducted to examine the influence of the selective
      delta-opioid receptor antagonist naltrindole upon the rewarding effects of
      cocaine. Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg
      per infusion) on an FR2 schedule of reinforcement. Dose-response and antagonist
      testing commenced once stable rates of cocaine SA were achieved. For antagonist
      testing, rats received naltrindole (0.03-10.0 mg/kg, IP) 30 min prior to the
      start of 2-h SA sessions. SA behavior in response to cocaine delivery (0.25 and
      1.0 mg/kg per infusion) was then determined. Naltrindole in doses of 0.03-3.0
      mg/kg did not alter the number of cocaine infusions taken by the rats. A higher
      dose of naltrindole (10.0 mg/kg), which markedly depressed locomotor activity,
      resulted in a 16% reduction of cocaine (0.25 mg/kg per infusion) SA behavior.
      When SA sessions were terminated and naltrindole (1.0 mg/kg) was administered
      repeatedly for 3 days, no alterations in the re-acquisition of cocaine SA were
      seen. Place conditioning studies also failed to find an effect of naltrindole
      (0.1-3.0 mg/kg) on cocaine (10 mg/kg)-induced conditioned place preferences.
      Naltrindole, by itself, did not induce significant place conditioning.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8539324
TI  - Presynaptic dopamine-glutamate interactions in the nucleus accumbens regulate
      sensorimotor gating.
AB  - Prepulse inhibition (PPI) is the normal reduction in startle reflex that occurs
      when a startling stimulus is preceded by a weak prepulse. PPI is reduced in
      patients with schizophrenia and in rats after central dopamine (DA) activation.
      The DA agonist-induced disruption of PPI in rats may thus model some features of
      impaired sensorimotor gating in schizophrenia. Ascending DAergic and descending
      glutamatergic fibers converge within the nucleus accumbens (NAC), and
      interactions at this DA-glutamate interface have been implicated in the
      pathophysiology of schizophrenia. In this study, we examined the role of NAC DA
      glutamate interactions in the regulation of PPI in rats. Intra-NAC infusion of
      the non-NMDA antagonist, CNQX, attenuated the PPI-disruptive effects of d
      amphetamine (AMPH), but CNQX did not affect PPI when injected alone, nor did it
      reverse the PPI-disruptive effects of the direct D2/D3 agonist quinpirole. Intra
      NAC infusion of the non-NMDA agonist AMPA significantly reduced PPI. The PPI
      disruptive effects of AMPA were blocked by haloperidol and by 6-hydroxydopamine
      (6OHDA) lesions of the NAC. These data suggest that the PPI-disruptive effects of
      AMPH are dependent on tonic non-NMDA receptor activation in the NAC, and that non
      NMDA receptor activation in the NAC results in a DA-dependent reduction in PPI.
      The parsimonious interpretation of these data is that non-NMDA glutamate
      receptors in the NAC facilitate presynaptic DA function, and that this DA
      glutamate interaction is a critical regulatory substrate of sensorimotor gating.

PMID- 8539326
TI  - Effects of flumazenil on recovery sleep and hormonal secretion after sleep
      deprivation in male controls.
AB  - The effects of flumazenil, a benzodiazepine antagonist, on the sleep
      electroencephalogram (EEG) and neuroendocrine secretion in early morning recovery
      sleep (0500-0800 hours) following sleep deprivation (SD; 2300-0500 hours) were
      studied in seven healthy men. SD induced an increase in slow wave sleep (SWS), a
      decrease in sleep onset latency (SOL), an enhancement of EEG delta and theta
      power in non-rapid-eye-movement sleep, an increase in plasma human growth hormone
      (GH) concentration, and a decrease in plasma cortisol levels in recovery sleep
      (0500-0800 hours). Plasma GH, but neither plasma cortisol nor
      adrenocorticotrophic hormone (ACTH) concentration was attenuated during SD as
      compared to sleep (2300-0445 hours). The administration of flumazenil (3 x 1 mg
      intravenously) during recovery sleep resulted in an inhibition in SWS, an
      increase in stage 2 sleep, a selective reduction in delta and theta power, and a
      tendency to prolongation of SOL. Plasma GH concentration was decreased but plasma
      cortisol and ACTH remained unaffected. Since the SD-induced changes in sleep EEG
      and plasma GH secretion were antagonized by flumazenil, it is suggested that
      electrophysiological and hormonal effects of SD are mediated at least in part
      through GABAergic mechanisms.

PMID- 8539327
TI  - Overnight caffeine abstinence and negative reinforcement of preference for
      caffeine-containing drinks.
AB  - It has been suggested that liking for the taste, flavour and aroma of, for
      example, coffee and tea is acquired through the process of classical
      conditioning, involving association of these orosensory cues with the
      psychopharmacological consequences of caffeine ingestion. Accordingly, this study
      investigated caffeine reinforcement by assessing changes in preference for a
      novel drink consumed with or without caffeine. Particular care was taken to use
      "ecologically valid" procedures; that is, overnight caffeine abstinence followed
      by a cup-of-coffee equivalent dose of caffeine (70 mg) at breakfast. Caffeine had
      no significant effects on drink preference or mood in subjects with habitually
      low intakes of caffeine. In contrast, moderate users of caffeine developed a
      relative dislike for the drink lacking caffeine and showed somewhat lowered mood
      following overnight caffeine abstinence (e.g., less lively, clearheaded and
      cheerful), which was significantly improved by caffeine. These together with
      other recent results strongly suggest that, in everyday life, caffeine
      reinforcement can occur as the result of the alleviation by caffeine of the
      adverse effects of overnight caffeine abstinence (negative reinforcement). They
      also demonstrate the utility of this flavour-conditioning procedure, which could
      be applied in the wider investigation of the reinforcing properties of drugs.

PMID- 8539328
TI  - Kynurenic acid and 5,7-dichlorokynurenic acids improve social and object
      recognition in male rats.
AB  - The present study describes the effect of kynurenic (KYNA) and 5,7
      dichlorokynurenic (DCKA) acids, acting as selective antagonists at the glycine
      site on the NMDA receptor complex, upon short-term memory of male rats.
      Oxiracetam (OXIR) or pramiracetam (PRAM) were used as reference compounds. In the
      social recognition test, adult animals were injected SC with a drug or vehicle
      immediately after the first exposure to a juvenile male, 21-24 days old, and
      reexposed to the same or a novel juvenile 120 min later. Time spent by adults in
      social investigation of juveniles was measured. Animals treated with KYNA or DCKA
      (0.3, 3 and 30 mg/kg in both cases) and OXIR (30 and 60 mg/kg) had significantly
      reduced investigation time when reexposed to the same juvenile as compared to
      controls. No reduction of investigation time was found in those drugged animals
      reexposed to a novel juvenile. The findings suggest that KYNA and DCKA improved
      retention of memory for olfactory stimuli in adult male rats. In the object
      recognition test, the duration of exploration of two identical objects during the
      sample trial and the familiar and a new object during the choice trial, performed
      60 min later, was evaluated. Drugs or vehicles were administered SC 30 min prior
      to the sample trial. On choice one, animals treated with KYNA or DCKA (0.6 and 30
      mg/kg in both cases) and PRAM (30 mg/kg) spent more time in exploring a new
      object than the familiar one as compared to controls. This suggests that the
      drugged animals were able to remember the familiar object.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8539329
TI  - Effects of microinjections of mu and kappa receptor agonists into the dorsal
      periaqueductal gray of rats submitted to the plus maze test.
AB  - Several lines of evidence have shown that aversive states are under the influence
      of opioid mechanisms in the dorsal periaqueductal gray (DPAG). In order to
      characterize the type of opioid receptors involved in these effects in this work
      we injected DAMGO and U50,488H, mu and kappa selective agonists, respectively,
      directly in this structure. Rats implanted with chemitrode in the DPAG were
      submitted to the elevated plus maze test for 5 min. The effects of DAMGO (0.1-1
      nmol/0.2 microliter) and U50,488H (1-10 nmol/0.2 microliter) following
      administration into DPAG were studied. Low doses of DAMGO (0.1 and 0.3 nmol)
      caused dose-dependent increases in the number of entries and time spent in the
      open arms while an overall deficit in the exploratory activity was produced by
      the higher dose used (1.0 nmol). Clear aversive effects were observed following
      the administration of U50,488H in the DPAG. The antiaversive effects of 0.3 nmol
      DAMGO were inhibited by the intraperitoneal administration of the mu receptor
      antagonist naltrexone (2.0 mg/kg, IP) whereas the aversive effects of 5.0 nmol
      U50,488H were antagonized by the selective kappa receptor antagonist nor
      binaltorphimine (1.0 mg/kg, IP). It is suggested that activation of mu receptors
      inhibit and kappa receptors enhance the neural substrate of aversion in the DPAG.

PMID- 8539330
TI  - Haloperidol prevents ethanol-stimulated locomotor activity but fails to block
      sensitization.
AB  - The effect of the dopamine receptor antagonist haloperidol on the development of
      sensitization to ethanol-induced increases in locomotor activity was examined in
      DBA/2J mice. In Experiment 1, different groups of mice were given saline or
      ethanol (2 g/kg) immediately before each of four locomotor activity sessions (48
      h intervals), and 1 h after pretreatment with saline, 0.10 or 0.15 mg/kg
      haloperidol. During a subsequent test, mice showed locomotor sensitization
      despite blockade of ethanol stimulated activity by haloperidol on the first
      conditioning trial. Moreover, test session activity was reduced in subjects that
      had previously received haloperidol, even though haloperidol was not present
      during testing. The second experiment examined the nature of the latter finding
      by comparing subjects that received equal exposure to haloperidol but differed in
      the pairing of its administration with the activity chambers. After four
      conditioning trials, each group was tested in the absence of haloperidol. Mice
      that had previously received haloperidol paired with the activity chambers were
      less active than control groups, suggesting development of a conditioned
      suppression of activity. Overall, these results suggest a dissociation of the
      neurobiological mechanisms that mediate the acute locomotor stimulant effects of
      ethanol and those mediating sensitization. Further, these studies illustrate the
      importance of antagonist-alone control groups that assess the possible influence
      of associative learning induced by the antagonist itself.

PMID- 8539331
TI  - Comparative pharmacology of nicotine and ABT-418, a new nicotinic agonist.
AB  - ABT-418, a novel cholinergic ligand, was reported to possess potent cognitive
      enhancing and anxiolytic properties in animal models with reduced side effects
      (Decker et al. 1994; Garvey et al. 1994) suggesting selectivity of effects. In
      this study, the binding properties of ABT-418 to [3H]-nicotine sites were
      evaluated and its pharmacology investigated in different tests in laboratory
      animals. ABT-418 binds with high affinity to 3H-nicotine binding sites in the
      brain with, however, a Ki (6 nM) less than that of nicotine (four-fold). In
      addition, it acts as a full nicotinic agonist in producing hypomotility,
      hypothermia and antinociception in mice and engendering nicotine-like responding
      in rat drug discrimination. The potency of ABT-418 is three to four times less
      than that of nicotine in all of the animal models, except for hypothermia. In
      addition, its behavioral effects are completely blocked by mecamylamine, a non
      competitive nicotinic antagonist. Although activation of nicotinic receptors by
      ABT-418 produced several behavioral and pharmacological effects, our results do
      not suggest high selectivity of different effects as reported by Decker et al.
      (1994) and Garvey et al. (1994). However, it should be noted that we did not
      perform some of these tests that produced effects at low doses (Decker et al.
      1994) and additional pharmacological studies are needed to establish its
      selectivity at multiple nicotinic receptors.

PMID- 8539332
TI  - Mianserin as a discriminative stimulus in rats: asymmetrical cross-generalization
      with scopolamine.
AB  - The present study was conducted to determine if the tetracyclic antidepressant
      mianserin could be established as a discriminative stimulus in rats. One group of
      rats was trained to discriminate mianserin (4.0 mg/kg, IP) from saline in a two
      lever drug discrimination procedure, and a second group of rats was trained to
      discriminate the muscarinic cholinergic antagonist scopolamine (0.25 mg/kg, IP)
      from saline. Generalization testing with the training drugs yielded an ED50 of
      0.502 mg/kg for the mianserin-trained rats and an ED50 of 0.048 mg/kg for the
      scopolamine-trained rats. Asymmetrical cross-generalization between mianserin and
      scopolamine was observed, because scopolamine produced mianserin-appropriate
      responding, but mianserin did not produce scopolamine-appropriate responding.
      This study is the first demonstration that rats can be trained to discriminate
      mianserin from saline and that antagonism of muscarinic cholinergic receptors is
      sufficient to produce mianserin-appropriate responding.

PMID- 8539334
TI  - Benzodiazepine (omega) receptor partial agonists and the acquisition of
      conditioned fear in mice.
AB  - It is well established that benzodiazepines can produce anterograde amnesia in
      humans and interfere with the acquisition of passive avoidance and spatial
      responses in rodents. However, the extent to which the disruption of learning is
      a secondary effect of the sedation produced by these drugs has not been clearly
      established. In order to investigate this question, the effects of several BZ
      (omega) receptor partial agonists were studied on the acquisition of conditioned
      fear (passive avoidance learning) in mice. As these drugs have been shown to
      produce anticonvulsant and anxiolytic-like effects without sedation or depression
      of motor activity, it was of interest to see whether they could disrupt learning.
      Clear effects on the acquisition of conditioned fear were produced by imidazenil
      (0.01-1.0 mg/kg), divaplon (1-60 mg/kg), ZK 91296 (3-60 mg/kg), and Ro 17-1812
      (0.1-10 mg/kg). However, bretazenil (0.1-10 mg/kg) did not produce statistically
      significant effects. Only the high dose of imidazenil (1.0 mg/kg) decreased
      levels of exploratory behaviour. These results show that BZ (omega) receptor
      partial agonists without apparent sedative actions can disrupt fear learning,
      indicating that the effects of this class of drugs on passive avoidance learning
      can be dissociated from sedation. The reasons for the observed differences
      between the different compounds studied are unclear at present and may be related
      to differences in intrinsic activity or receptor subtype selectivity.

PMID- 8539333
TI  - 5-HT1A receptor agonists: recent developments and controversial issues.
AB  - During the last decade, serotonin (5-HT)1A receptors have been a major target for
      neurobiological research and drug development. 5-HT1A receptors have been cloned
      and a variety of selective agonists, such as the aminotetraline 8-OH-DPAT and the
      pyrimidinylpiperazine ipsapirone, have become available. Demonstrations of
      apparent intrinsic activity of these ligands at 5-HT1A receptors, however, depend
      highly on the particular assay system. This may be due to the possible existence
      of receptor subtypes and to assay (or brain region)-dependent differences in
      receptor reserve and the nature of receptor-effector coupling. Nevertheless, the
      apparent intrinsic activity of 8-OH-DPAT seems to be higher (although possibly
      not yet maximal) than that of the pyrimidinylpiperazines. In the brain, 5-HT1A
      receptors are located presynaptically as somatodendritic receptors on 5-HT
      neurons and postsynaptically in particular limbic and cortical regions. Although
      it is generally accepted that presynaptic 5-HT1A receptors control 5-HT neuronal
      activity, recent evidence suggests an additional role of postsynaptic 5-HT1A
      receptors in cortex as part of a negative feedback loop. Anxiolytic and
      antidepressive properties of selective 5-HT1A receptor agonists have now been
      confirmed by clinical studies. Although it is well established that the latter
      properties depend on the agonistic activity of these compounds, the optimal level
      of intrinsic activity is still a matter of debate and may be dependent on the
      clinical indication. Such compounds may also have antiaggressive effects, and
      possibly anticraving effects (manifested by their alcohol intake-reducing effects
      in dependent animals), but the specificity of these so-called anti-impulsivity
      effects is still controversial and not yet tested clinically. Anticataleptic,
      antiemetic and neuroprotective properties have been demonstrated in different
      species. Behavioral studies on the mechanisms underlying the anxiolytic and
      antidepressive effects have examined the relative contribution of pre- and
      postsynaptic 5-HT1A receptors by means of local cerebral application and lesion
      techniques. Most evidence points towards a critical involvement of presynaptic
      receptors in the anxiolytic effects of 5-HT1A receptor agonists (although a
      possible contribution of postsynaptic receptors cannot be excluded). With regard
      to the antidepressive properties, a case can be made for the reverse; i.e., a
      strong involvement of postsynaptic receptors and a questionable contribution of
      presynaptic receptors. However, as the therapeutic effects of those 5-HT1A
      receptor (partial) agonists which have been tested clinically require repeated
      administration, attention has been directed increasingly towards chronic
      studies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8539335
TI  - Lack of effect of CCKB receptor antagonists in ethological and conditioned animal
      screens for anxiolytic drugs.
AB  - The effects of the CCKB receptor antagonists L-365,260, CI-988 and L-740,093, a
      new compound with improved bioavailability and CNS penetration, were assessed for
      anxiolytic-like effects in three rat anxiolytic screens sensitive to
      benzodiazepines, the elevated plus maze (EPM), conditioned suppression of
      drinking (CSD) and conditioned emotional response (CER) tests. In the EPM, L
      740,093 (0.1-1.0 mg/kg), L-365,260 (0.00001-10.0 mg/kg), and CI-988 (0.01-1.0
      mg/kg) did not increase the time spent on the open arms of the maze or the number
      of entries onto the open arms. In contrast, the benzodiazepine receptor partial
      agonist, bretazenil (0.3-10.0 mg/kg), significantly increased both the time spent
      on the open arms and the number of open arm entries. In the CSD and the CER
      tests, L-740,093 (0.1-1.0 mg/kg) L-365,260 (0.0001-0.1 mg/kg) and CI-988 (0.01
      10.0 mg/kg) failed to increase suppression ratios compared to the vehicle-treated
      control rats, whereas, the benzodiazepine receptor partial agonist FG 8205 (10.0
      mg/kg) (CSD) and bretazenil (0.3-3.0 mg/kg) (CER) both significantly increased
      suppression ratios compared to vehicle-treated control rats. In addition, L
      365,260 (1.0-50.0 mg/kg), CI-988 (0.1-10.0 mg/kg) and diazepam (0.1-1.0 mg/kg)
      were assessed in a squirrel monkey conflict procedure. Although diazepam
      significantly increased suppressed lever pressing rates, L-365,260 and CI-988
      were without effect. The present findings provide little support for the
      hypothesis that CCKB receptor antagonists have anti-anxiety effects in animals.

PMID- 8539337
TI  - Failure of CCK receptor ligands to modify anxiety-related behavioural suppression
      in an operant conflict paradigm in rats.
AB  - The effects of cholecystokinin (CCK) receptor ligands were studied in the rat
      safety signal withdrawal conflict procedure, an operant paradigm sensitive to
      both anxiolytic and anxiogenic compounds. In this procedure, behavioural
      suppression of lever pressing for food was induced by the withdrawal of a
      conditioned signal for safety without the usual presentation of a conditioned
      signal for danger. The compounds tested were selective CCK-B antagonists [CI-988
      (0.01-1 mg/kg SC), L-365,260 (0.004-2 mg/kg IP) and LY 262,691 (0.001-1 mg/kg
      SC)], CCK-B agonists [CCK-4 (0.01-1 mg/kg SC) and BC 264 (0.004-1 mg/kg IP)] and
      CCK-A antagonists [devazepide (0.001-1 mg/kg SC) and lorglumide (0.01-1 mg/kg
      SC)]. None of these drugs induced the expected behavioural effects, i.e. an
      anxiolytic-like release of the behavioural suppression with CCK-B and, possibly,
      CCK-A antagonists and/or a further reduction of lever pressing with CCK-B
      agonists, indicative of an anxiogenic-like potential. In contrast, the
      established anxiolytic lorazepam (0.06-0.25 mg/kg IP), as well as diazepam (2
      mg/kg IP) and buspirone (0.25 mg/kg SC) used as positive control drugs, released
      the suppression of pressing for food during the period associated with the safety
      signal withdrawal, whereas picrotoxin (1 mg/kg IP), used as an anxiogenic
      control, further reduced responding during this conflict period. The present
      results contrast with a series of published data suggesting the involvement of
      CCK processes in anxiety-related behaviour in rodent models such as the elevated
      plus-maze or the light:dark two compartment test, and in panic disorders in
      humans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539336
TI  - Effects of benzodiazepine receptor partial inverse agonists in the elevated plus
      maze test of anxiety in the rat.
AB  - The present series of experiments examined the effects of five benzodiazepine
      receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated
      plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to
      the open arms, as this has been shown to increase the sensitivity of the plus
      maze to anxiogenic-like drugs effects (Jones and Cole 1995). The drugs tested
      were FG 7142 (0-100 mg/kg), beta-CCE (0-30 mg/kg), ZK 132,556 (0-100 mg/kg), ZK
      90 886 (0-30 mg/kg) and Ro 15-4513 (0-30 mg/kg). In addition, to allow a
      comparison with previous studies, the effects of three reference substances, DMCM
      (0-2.5 mg/kg), pentylenetetrazol (PTZ; 0-30 mg/kg) and yohimbine (0-5 mg/kg),
      were also examined. These three reference compounds produced a dose-dependent
      reduction in the duration of open arm exploration and the total number of open
      arm entries, indicative of anxiogenic-like effects. DMCM produced significant
      effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5
      mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also
      reduced the duration of open arm exploration and the total number of arm entries.
      The minimally effective dose resulted in a receptor occupancy of approximately
      80%. Ro 15-4513 also produced anxiogenic-like effects, but only at a dose (30
      mg/kg) that resulted in a receptor occupancy of approximately 95%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8539338
TI  - Alcohol, anxiolytics and social stress in rats.
AB  - The main objective was to compare the anxiolytic-like profiles of alcohol,
      diazepam and gepirone along the stress intensity gradient which characterizes
      consecutive phases of a social confrontation. The acute social stress situation
      consisted of initially placing the experimental rat as an intruder into the
      homecage of a resident while the resident was not present, termed the
      "anticipatory" phase, thereafter permitting brief physical agonistic interactions
      with the re-introduced resident until the intruder was forced into a submissive
      supine posture and emitted ultrasonic vocalizations (USV), and eventually
      exposing the intruder to the resident's threats for 1 h, while being shielded
      from potential injurious attacks. The hyperthermia, measured via telemetry, in
      the "anticipatory" phase prior to defeat and in reaction to threats, was
      decreased by alcohol, gepirone and diazepam; alcohol and gepirone were also
      effective in attenuating "anticipatory" tachycardia. Alcohol, like gepirone and
      diazepam, also decreased defensive responses and ultrasonic vocalizations in the
      "anticipatory" phase of the confrontation, but none of these drugs affected
      defensive reactions to threats which immediately followed defeat. Gepirone had no
      systematic sedative effects throughout the confrontation; infact, it dose
      dependently reduced the stress-induced suppression of locomotor activity during
      the "anticipatory" phase. In contrast, at higher doses, alcohol as well as
      diazepam had marked sedative effects as evidenced by several behavioral
      parameters (i.e. lie, crouch, walk). The anxiolytic-like profile of hyperthermia,
      tachycardia, USV and defensive behavior in the "anticipatory" phase of the
      confrontation by alcohol, gepirone and diazepam contrasted with the lack thereof
      during the more intense reactive phase. This differential pattern of effects
      appears to be relevant to the clinical distinctions between anticipatory anxiety
      and other affective disturbances.

PMID- 8539339
TI  - Administration of antidepressants, diazepam and psychomotor stimulants further
      confirms the utility of Flinders Sensitive Line rats as an animal model of
      depression.
AB  - Flinders Sensitive Line (FSL) rats have been proposed as an animal model of
      depression because they resemble depressed humans in that they have elevated REM
      sleep, reduced activity, and increased immobility and anhedonia after exposure to
      stressors. The present paper reviews experiments on the drug treatment of FSL and
      control Flinders Resistant Line (FRL) rats related to their utility as an animal
      model of depression, and presents new information. FSL rats exhibited exaggerated
      immobility in the forced swim test which is counteracted by the tricyclic
      antidepressants imipramine and desipramine and the serotonin reuptake blocker
      sertraline; the low immobility exhibited by the FRL rats is generally unaffected
      by these compounds. In contrast to these "therapeutic" effects of well recognized
      antidepressants, lithium and bright light treatment did not alter the exaggerated
      immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats
      exhibited alterations in swim test immobility following chronic administration of
      the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic
      scopolamine (2 mg/kg), which typically reduce immobility after acute
      administration. However, it was found that the calcium channel blockers verapamil
      (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility
      in FSL rats following chronic administration, suggesting that these compounds
      need to be evaluated further in humans. Previous studies have indicated no
      differences between FSL and FRL rats evaluated in the elevated plus maze, either
      at baseline or after the administration of diazepam, suggesting that the FSL rat
      may not differ from controls in anxiety-related behavior. Another recently
      published study showed that the FSL rat also did not differ from normal Sprague
      Dawley rats in startle tests, indicating that the FSL rats do not exhibit
      behaviors shown in animal models of schizophrenia. These findings confirm the
      utility of FSL rats as an animal model of depression because the FSL rats do not
      appear to exhibit behaviors analogous to anxiety or schizophrenia and because
      they respond "therapeutically" to antidepressants and not psychomotor stimulants.

PMID- 8539341
TI  - Amphetamine analogs have differential effects on DRL 36-s schedule performance.
AB  - Amphetamine and related compounds have previously been shown to differentially
      release dopamine (DA) and serotonin (5HT) in vivo and in vitro. The purpose of
      this report is directly to compare five amphetamine analogs on differential
      reinforcement of low rate 36-s (DRL 36-s) schedule performance, and to determine
      whether the reported increases in dopamine and/or serotonin release induced by
      these drugs can be related to observed behavioral differences. Amphetamine (AMPH)
      and methamphetamine (METH) induced large increases in response rate,
      methylenedioxymethamphetamine (MDMA) and para-chloroamphetamine (PCA) caused
      small increases in response rate, while fenfluramine (FEN) had no effect on
      response rate. AMPH, METH, PCA and MDMA caused a dose-dependent decrease in
      reinforcement rate, and FEN had no effect on reinforcement rate. AMPH, METH, and
      PCA but not FEN, shifted the peak of the inter-response time (IRT) distribution
      toward shorter intervals, MDMA decreased peak location only at the highest dose.
      All five drugs caused a dose-dependent decrease in peak area, indicating a loss
      of schedule control on the DRL 36-s schedule. Consistent with in vitro and in
      vivo release studies, the differential results of these five drugs on DRL 36-s
      schedule performance suggest a predominant dopamine role for AMPH and METH, a
      predominant serotonin role for FEN, and different degrees of combined
      dopaminergic and serotonergic roles for MDMA and PCA in the mediation of the
      task.

PMID- 8539340
TI  - Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics.
AB  - A continuing challenge for preclinical research on anxiolytic drugs is to capture
      the affective dimension that characterizes anxiety and aggression, either in
      their adaptive forms or when they become of clinical concern. Experimental
      protocols for the preclinical study of anxiolytic drugs typically involve the
      suppression of conditioned or unconditioned social and exploratory behavior
      (e.g., punished drinking or social interactions) and demonstrate the reversal of
      this behavioral suppression by drugs acting on the benzodiazepine-GABAA complex.
      Less frequently, aversive events engender increases in conditioned or
      unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear
      potentiated startle). More recently, putative anxiolytics which target 5-HT
      receptor subtypes produced effects in these traditional protocols that often are
      not systematic and robust. We propose ethological studies of vocal expressions in
      rodents and primates during social confrontations, separation from social
      companions, or exposure to aversive environmental events as promising sources of
      information on the affective features of behavior. This approach focuses on vocal
      and other display behavior with clear functional validity and homology. Drugs
      with anxiolytic effects that act on the benzodiazepine-GABAA receptor complex and
      on 5-HT1A receptors systematically and potently alter specific vocalizations in
      rodents and primates in a pharmacologically reversible manner; the specificity of
      these effects on vocalizations is evident due to the effectiveness of low doses
      that do not compromise other physiological and behavioral processes. Antagonists
      at the benzodiazepine receptor reverse the effects of full agonists on
      vocalizations, particularly when these occur in threatening, startling and
      distressing contexts. With the development of antagonists at 5-HT receptor
      subtypes, it can be anticipated that similar receptor-specificity can be
      established for the effects of 5-HT anxiolytics.

PMID- 8539342
TI  - Active behaviors in the rat forced swimming test differentially produced by
      serotonergic and noradrenergic antidepressants.
AB  - This study demonstrated that distinct patterns of active behaviors are produced
      by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5
      HT) uptake in the rat forced swimming test (FST). A behavior sampling technique
      was developed to score the active behaviors swimming, climbing and diving, as
      well as immobility. The rat's behavior was recorded at the end of each 5-s period
      during the test session. The sampling technique was both reliable, as
      demonstrated by test-retest reliability and inter-rater reliability, and valid,
      as shown by comparison to the timing of behavior durations. Five different
      antidepressant drugs which block monoamine uptake and two 5-HT1A receptor
      agonists were shown to decrease immobility in the FST; however, they produced
      distinct patterns of active behaviors. The selective NE uptake inhibitors
      desipramine and maprotiline selectively increased climbing, whereas the selective
      serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine
      selectively increased swimming. The 5-HT1A receptor agonists 8-OH-DPAT and
      gepirone also selectively increased swimming. These results show that:1) SSRIs
      are not false negatives in the FST; 2) at least two behaviorally distinct
      processes occur in the FST; and 3) enhancement of NE neurotransmission may
      mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may
      mediate swimming.

PMID- 8539343
TI  - A comparison of the behavioral effects of minaprine, amphetamine and stress.
AB  - Different types of clinically effective antidepressants prevent the behavioral
      effects of experimental stress, and some of these treatments affect mesolimbic
      dopamine (DA) functioning. Animal studies have demonstrated that repeated
      psychostimulant administration and repeated or chronic stressful experiences also
      affect mesolimbic DA functioning. These results could suggest homologies among
      stress, psychostimulants and antidepressants. The present experiments show that
      either repeated stress (120 min restraint daily for 10 consecutive days) or
      subchronic treatment with the antidepressant minaprine (5 mg/kg daily for 10
      consecutive days) significantly reduced the inhibitory effect of 120 min of
      restraint on climbing, a behavioral response dependent on mesolimbic DA
      functioning. However, the antidepressant did not induce the altered sensitivity
      of presynaptic DA receptors promoted by repeated stress. Chronic stressful
      experience (13 days of food restriction) and repeated amphetamine (2.5 mg/kg
      daily for 10 consecutive days) were as effective as subchronic minaprine in
      reducing immobility in the Porsolt's swimming test. However, whilst both stress
      and amphetamine enhanced struggling, minaprine promoted swimming. Finally,
      chronically stressed mice and mice pretreated with amphetamine showed enhanced
      sensitivity to amphetamine-induced locomotion, whilst this effect was absent in
      animals pretreated with the antidepressant. These results indicate that although
      chronic and repeated stress as well as amphetamine have some antidepressant-like
      behavioral effects, their mode of action could be different from that of
      clinically active substances.

PMID- 8539344
TI  - The ambivalent behaviour "stretched approach posture" in the rat as a paradigm to
      characterize anxiolytic drugs.
AB  - The effect of various psychotropic drugs on the ambivalent behaviour "stretched
      approach posture" (SAP) in the rat was assessed. SAP was elicited after a mild
      startle reaction due to physical contact with an electrified prod at one end of a
      straight runway. Using ethological observation methods, SAP as well as intention
      movements, prod contact, crossings, rearing, exploration, grooming and immobility
      were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam
      and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5
      HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced
      SAP. Except for alprazolam, these drugs also reduced intention movements. In
      addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP
      and intentions with concomitant reductions of crossings (nonspecific
      antiambivalent effects) were established for the alpha 2-adrenoceptor agonist
      clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine
      suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor
      imipramine did not significantly affect SAP or intentions, but reduced crossings.
      The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142
      and DMCM, and the alpha 2-adrenoceptor antagonist yohimbine, to all of which
      putative anxiogenic effects have been ascribed, had no effect on SAP directed
      towards the prod. m-CPP, however, produced an increase in the stretched posture
      directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly
      enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect
      anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol
      false positively reduced SAP while increasing exploration. The dopamine-D2
      receptor antagonist haloperidol and the catecholamine releaser dl-amphetamine had
      no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine
      reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C
      receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the
      CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site
      antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this
      paradigm using single doses. In conclusion, SAP and intention movements were
      reduced selectively by anxiolytic agents from different classes, including
      benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake
      inhibitor, whereas an alpha 2-adrenoceptor agonist and a MAO inhibitor reduced
      SAP non-selectively. SAP in relation to other behaviours may therefore serve as a
      valuable paradigm to characterize anxiolytic drugs.

PMID- 8539345
TI  - Preferences for ethanol and diazepam in anxious individuals: an evaluation of the
      self-medication hypothesis.
AB  - The self-medication hypothesis of addictive disorders postulates that individuals
      with psychiatric symptoms use drugs to alleviate their symptoms. Although
      commonly cited to explain the etiology of substance abuse, self-medication has
      not been experimentally validated. This study evaluated one version of the self
      medication hypothesis by formulating it into a testable hypothesis: are highly
      anxious volunteers more likely to self-administer anxiolytic drugs than non
      anxious controls. Anxious (ANX, n = 22) and control (CTL, n = 23) subjects
      participated in two double-blind placebo-controlled experiments, one testing
      ethanol (0.8 g/kg) and the other testing diazepam (20 mg). Subjects sampled and
      then chose between ethanol and placebo in one experiment, and diazepam and
      placebo in the other. The main dependent measures were choice of drug over
      placebo and subjective responses to the drugs. Ethanol decreased self-reported
      anxiety in ANX subjects, but ANX subjects did not choose ethanol more often than
      CTL subjects. Diazepam did not measurably reduce anxiety, but ANX subjects
      nevertheless chose diazepam more often than did CTL subjects. Thus, there were
      some differences in drug responses between the ANX and CTL subjects, and the
      study provided limited support for the self-medication hypothesis. However, drug
      choice was not directly related to anxiolytic drug effects with either ethanol or
      diazepam. The procedure may be used to test other formulations of the self
      medication hypothesis (e.g., examining other psychiatric risk factors).

PMID- 8539346
TI  - Portable chest radiography techniques and teleradiology.
AB  - Despite the large number of portable examinations performed, the quality of
      bedside radiography is highly variable and has lagged behind the rapid advances
      in other fields of medical imaging. The authors discuss the technical factors of
      image production in relation to methods for improving image quality in portable
      radiography. Digital radiography has significant practical technical advantages
      in portable applications and also allows transmission and accessibility of images
      on a computer network.

PMID- 8539347
TI  - Radiologic evaluation of the patient after cardiac surgery.
AB  - The chest radiograph traditionally has played a central role in the preoperative
      and postoperative care of cardiac surgery patients. Familiarity with the
      preoperative evaluation, the basics of the process of cardiopulmonary bypass, and
      the nuances of care in the postoperative period enables the radiologist to
      provide a more meaningful radiologic consultation.

PMID- 8539348
TI  - Noncardiac thoracic surgical procedures. Definitions, indications, and
      postoperative radiology.
AB  - The radiologist should be familiar with the various operative procedures of the
      chest to accurately interpret routine postoperative radiologic studies. This also
      will assist them in the detection of common iatrogenic problems and postoperative
      complications such as bleeding, air leak, and infection. Furthermore, knowledge
      of serious and specific complications such as cardiac herniation and post
      pneumonectomy syndrome can help the radiologist play an active role in the
      postoperative care of such patients.

PMID- 8539349
TI  - Interventional procedures in the intensive care unit patient.
AB  - Image-guided interventional techniques have markedly altered the management of
      many cardiothoracic problems in the intensive care unit. These techniques are
      less invasive, more patient friendly, and cost-effective. This article covers
      venous line placement and management, transpleural and transpulmonary biopsy and
      drainage procedures and interventions for variceal bleeding, massive hemoptysis,
      massive pulmonary embolism, and veno-occlusive disease.

PMID- 8539350
TI  - Evaluation of the abdomen in sepsis of unknown origin.
AB  - The radiologic evaluation of sepsis of unknown origin has changed dramatically
      since the introduction of cross-sectional imaging. Interventional procedures such
      as abscess drainage, cholecystostomy, biliary drainage, nephrostomy, and fluid
      aspiration have reduced the morbidity and mortality associated with occult
      sources of sepsis. This article examines some of the common etiologies and
      treatments of sepsis in the hospitalized patient.

PMID- 8539352
TI  - Congestive heart failure and adult respiratory distress syndrome. New insights
      using computed tomography.
AB  - CT has brought new insights into our understanding of the patient with acute
      respiratory distress, pulmonary edema, and adult respiratory distress syndrome.
      This article documents some of the physiologic and imaging information gained
      from axial imaging of the critically ill.

PMID- 8539351
TI  - Accuracy and efficacy of chest radiography in the intensive care unit.
AB  - In summary, the chest radiograph has only moderate accuracy in visualizing
      opacification caused by cardiopulmonary abnormalities and may be quite
      nonspecific as to etiology, whereas it has high diagnostic accuracy for detecting
      malpositioning of tubes and lines. While focal parenchymal abnormalities are
      usually visualized on chest radiographs, identification of concomitant
      abnormalities when ARDS or PE already exist is more difficult. Atelectasis,
      aspiration, pneumonia, pulmonary hemorrhage, pulmonary thromboembolism, atypical
      cardiogenic edema, asymmetric ARDS, and neoplasms may be indistinguishable.
      Repeat chest radiographs and different views may be helpful, as the progression
      and time course of various etiologies can be quite different. On the other hand,
      Winer-Muram et al found that review of prior radiographs and clinical data did
      not improve the diagnostic accuracy for either ARDS or pneumonia. Pleural
      effusions may even be difficult to distinguish from parenchymal processes,
      particularly when the patient is in the supine position. Additional views with
      the patient in a different position--semi-erect, decubitus, or cross-table
      lateral--may be of assistance. In most cases, pneumothorax is readily detected.
      Additional studies such as the decubitus view occasionally may be necessary for
      further evaluation when there is uncertainty about the findings. Subcutaneous air
      is readily visualized radiographically. Pneumomediastinum and interstitial
      pulmonary emphysema may be more difficult to see. It is well known that CT allows
      visualization of much smaller abnormal air collections than radiography. Despite
      this lack of sensitivity and specificity of chest films, studies have shown that
      up to 65% of daily films in the ICU reveal significant and/or unsuspected
      abnormalities that may change the patient's diagnosis or management. Based on
      these results, the consensus opinion of the ACR Expert Panel found that daily
      chest radiographs are indicated on patients with acute cardiopulmonary problems
      and those receiving mechanical ventilation. Patients who require cardiac
      monitoring but are otherwise stable require only an initial admission film.
      Additional radiographs are indicated only when a new device is placed or when
      there is a specific question regarding cardiopulmonary status. It is also
      noteworthy that despite the chest film being the most commonly ordered radiologic
      examination for inpatients, there are no comprehensive studies evaluating its
      cost-effectiveness. Although several studies have done a very limited cost
      accounting of the potential savings by eliminating routine films in the
      evaluation of specific subsets of patients, overall impact on patient outcome has
      not been investigated. Thus, a true assessment of cost-effectiveness has yet to
      be determined.

PMID- 8539353
TI  - Nosocomial pneumonia.
AB  - Nosocomial pneumonia continues to be a major problem plaguing hospitalized
      patients, especially those on ventilators. Gram-negative bacteria and S. aureus
      are the most common causitive organisms. Alteration of the normal oropharyngeal
      flora and contamination of the respiratory tract from the pharynx and stomach are
      now recognized to be important factors in its development. As there is no
      definitive diagnostic test, nosocomial pneumonia remains a clinical diagnosis;
      however bronchoscopy with protected specimen brush cultures and BAL are
      diagnostic methods under study. Noninvasive radiologic examinations and clinical
      criteria have poor specificity in diagnosis.

PMID- 8539354
TI  - Barotrauma.
AB  - Barotrauma remains a significant complication of mechanical ventilation,
      particularly in ARDS. A number of alternative techniques for mechanical
      ventilation are being investigated with the purpose of minimizing ventilator
      related lung injury and air leak phenomena while maintaining adequate
      oxygenation. Among them pressure-controlled inverse-ratio ventilation and
      extracorporeal carbon dioxide removal have not resulted in a definite reduction
      of barotrauma thus far. The radiologist plays an important role in the early
      recognition of barotrauma and may assist in the treatment of its sequelae.

PMID- 8539355
TI  - Aspiration in patients in critical care units.
AB  - Pulmonary aspiration is a serious cause of morbidity and mortality in patients
      with a depressed sensorium, patients with neuromuscular discoordination, or
      patients having a structural disorder of the upper aerodigestive tract. This
      problem is relatively frequent in patients in critical care units and other areas
      where anesthesia is used. The most common manifestations of pulmonary aspiration
      are chemical pneumonitis, pleuropulmonary infection, and acute airway
      obstruction. The clinical and radiographic manifestations of pulmonary aspiration
      are nonspecific and diagnosis depends on a consistent constellation of clinical
      and radiographic criteria.

PMID- 8539356
TI  - Pulmonary complications after bone marrow transplantation.
AB  - Many of the pulmonary complications that we have described have a nonspecific
      radiographic appearance. The most crucial information for proper interpretation
      of the chest radiographs is the chronologic onset of radiographic abnormalities
      after transplantation. Before and immediately after engraftment, local peripheral
      opacities accompanied by a surrounding rim of edema are regarded as fungal
      infections, and therapy with granulocyte transfusions and amphotericin B is
      initiated. Diffuse interstitial thickening is likely to represent edema,
      pulmonary hemorrhage, bacterial infection, or ARDS rather than CMV or P. carinii
      pneumonia in the neutropenic host. After engraftment, diffuse interstitial
      processes become the predominant lung abnormalities. In allogeneic transplant
      patients who are serologically positive for CMV or who receive serologically
      positive donor marrow for CMV, pneumonitis caused by this virus is perhaps the
      most common treatable lung infection. Idiopathic interstitial pneumonias present
      in a similar fashion to CMV pneumonia; however, the response to corticosteroid
      therapy is only occasionally gratifying. The onset of nodular opacities in this
      period may be due to a number of disorders, such as opportunistic infection,
      BOOP, PTLPD or recurrent tumor. Open lung biopsy usually is required for
      definitive diagnosis.

PMID- 8539357
TI  - Pseudomembranous colitis.

PMID- 8539358
TI  - First, do no harm.

PMID- 8539359
TI  - Wallstents for the treatment of extrinsic malignant ureteral obstruction: midterm
      results.
AB  - PURPOSE: To test the clinical efficacy of metal stents in the treatment of
      malignant ureteral obstruction and to maximize the effectiveness of the method.
      MATERIALS AND METHODS: Fifty-four malignant stenoses of the ureter were treated
      in 40 patients by implantation of a self-expandable permanent endoluminal stent
      (SPES). RESULTS: The mean follow-up time was 10.5 months (range, 1-44 months).
      Recanalization was possible in all but one ureter. Fifty-one ureters were kept
      sufficiently open during the follow-up period. Fifty-one percent needed no
      further intervention, whereas 49% needed reintervention to reestablish patency.
      Three ureters in the latter group finally had to be abandoned. The primary
      patency after 12 months was 31% according to the Kaplan-Meier estimation. The
      survival rates of the patients were 40% after 12 months and 22% after 24 months
      and were unrelated to stent placement. CONCLUSION: Since no major complications
      occurred and hydronephrosis and its sequelae could be prevented in most cases
      during the observation period, the authors conclude that the implantation of a
      SPES into the ureter is a safe and effective method for the palliative treatment
      of tumor-associated ureteral strictures.

PMID- 8539360
TI  - Adnexal masses: transvaginal US and gadolinium-enhanced MR imaging assessment of
      intratumoral structure.
AB  - PURPOSE: To evaluate the accuracy of transvaginal ultrasound (US) and gadolinium
      enhanced magnetic resonance (MR) imaging in the assessment of the intratumoral
      structure of an adnexal mass. MATERIALS AND METHODS: The population comprised 82
      patients with an adnexal mass who underwent both transvaginal US and gadolinium
      enhanced MR imaging and had surgical confirmation. The findings from both
      modalities were compared retrospectively with those of surgery. RESULTS: The
      sensitivity, specificity, and accuracy were 100%, 98%, and 99% with MR imaging
      and were 97%, 46%, and 68% with transvaginal US for the identification of solid
      tissue in the masses. Transvaginal US exhibited many (n = 25) false-positive
      results, especially in evaluation of lesions filled with blood or fatty tissue
      and small echogenic excrescences adherent to the wall, such as blood or fatty
      tissue. CONCLUSION: Both transvaginal US and gadolinium-enhanced MR imaging were
      highly sensitive in identification of solid components within an adnexal mass.
      Gadolinium-enhanced MR imaging was specific, whereas transvaginal US was
      nonspecific.

PMID- 8539361
TI  - Pseudoangiomatous stromal hyperplasia: mammographic, sonographic, and clinical
      patterns.
AB  - PURPOSE: To analyze the mammographic, ultrasonographic (US), and clinical
      patterns of pseudoangiomatous stromal hyperplasia (PASH). MATERIALS AND METHODS:
      Preoperative mammographic and US images, clinical records, and histologic
      assessments were reviewed in seven cases of PASH as the sole component or
      dominant stromal component of a clinically or mammographically defined mass
      lesion. In five, a PASH tumor was diagnosed at image-guided 14-gauge core-needle
      biopsy; in two, it was diagnosed at surgical excisional biopsy. RESULTS: Four
      women were premenopausal, two were postmenopausal, and one 40-year-old patient
      had iatrogenic primary amenorrhea. Four of seven masses were palpable; three were
      discovered at mammography. Four masses enlarged over 6 months to 5 years. At
      mammography, all masses lacked calcifications; six were well defined, and one was
      spiculated. One was inapparent at US; the remaining six were well defined and
      hypoechoic. CONCLUSION: The diagnosis of this rare lesion with image-guided
      breast biopsy or surgical biopsy is consistent with a well-defined uncalcified
      mass at mammography and a solid hypoechoic mass at US, usually in a premenopausal
      woman.

PMID- 8539362
TI  - Benign and malignant phyllodes tumors: mammographic and sonographic findings.
AB  - PURPOSE: To characterize imaging findings that suggest the benign or malignant
      histologic nature of phyllodes tumors. MATERIALS AND METHODS: Clinical and
      imaging findings were retrospectively reviewed in 46 women with 51 phyllodes
      tumors (32 benign, 19 malignant) identified at preoperative mammography. Thirty
      of these tumors were also evaluated with preoperative sonography. RESULTS:
      Mammography showed nonspiculated soft-tissue masses in 49 tumors. Four masses
      contained calcifications; three of these masses were benign. The tumors were 1-20
      cm in diameter; tumors 3 cm or larger were statistically significantly more
      likely to be malignant (P < .004). Sonography showed solid, hypoechoic masses in
      28 cases. At sonography, cystic areas were more often seen in malignant than in
      benign tumors, but the difference was not statistically significant. CONCLUSION:
      There is substantial overlap in the imaging characteristics of benign and
      malignant phyllodes tumors. A tumor diameter of 3 cm or greater appears to be
      associated with a higher likelihood of malignancy.

PMID- 8539364
TI  - RSNA EJ: a supplement to RadioGraphics and a new venture in radiologic
      publishing.

PMID- 8539363
TI  - Nova Scotia Breast Screening Program experience: use of needle core biopsy in the
      diagnosis of screening-detected abnormalities.
AB  - PURPOSE: To evaluate a mammography screening program that uses a
      multidisciplinary team approach and needle core biopsy. MATERIALS AND METHODS: A
      total of 10,000 asymptomatic women (aged 40-74 years) underwent screening in the
      Nova Scotia Breast Screening Program between June 1991 and April 1994. Women aged
      50-69 years were the target group. All mammograms were read by one of four
      radiologists. Patients with abnormal screening findings underwent work-up, which
      included needle core biopsy, at one of two diagnostic centers. RESULTS: Of 10,000
      women, 2,794 were aged 40-49 years; 4,097, 50-59 years; 2,941, 60-69 years; and
      168, 70-74 years, with 3.9, 6.4, 12.2, and 23.8 cancers detected per 1,000
      patients, respectively. The overall rate was 7.7 cancers detected per 1,000
      patients. Abnormalities were detected at screening in 838 patients (8.4%), 181 of
      whom underwent open surgery, with malignancy diagnosed in 77 (42%). Sixty-one
      (79%) of 77 patients had stage 0 or I cancer. In 43 (72%) of 60 patients in whom
      node status was assessed, findings were negative. CONCLUSION: A screening program
      with needle core biopsy and a multidisciplinary team approach to diagnosis is
      effective.

PMID- 8539365
TI  - Artificial neural network: improving the quality of breast biopsy
      recommendations.
AB  - PURPOSE: To evaluate the performance and inter- and intraobserver variability of
      an artificial neural network (ANN) for predicting breast biopsy outcome.
      MATERIALS AND METHODS: Five radiologists described 60 mammographically detected
      lesions with the American College of Radiology Breast Imaging Reporting and Data
      System (BI-RADS) nomenclature. A previously programmed ANN used the BI-RADS
      descriptors and patient histories to predict biopsy results. ANN predictive
      performance was compared with the clinical decision to perform biopsy. Inter- and
      intraobserver variability of radiologists' interpretations and ANN predictions
      were evaluated with Cohen kappa analysis. RESULTS: The ANN maintained 100%
      sensitivity (23 of 23 cancers) while improving the positive predictive value of
      biopsy results from 38% (23 of 60 lesions) to between 58% (23 of 40 lesions) and
      66% (23 of 35 lesions; P < .001). Interobserver variability for interpretation of
      the lesions was significantly reduced by the ANN (P < .001); there was no
      statistically significant effect on nearly perfect intraobserver reproducibility.
      CONCLUSION: Use of an ANN with radiologists' descriptions of abnormal findings
      may improve interpretation of mammographic abnormalities.

PMID- 8539366
TI  - Partial liquid ventilation with perflubron during extracorporeal life support in
      adults: radiographic appearance.
AB  - PURPOSE: To describe the radiographic appearance of perflubron-filled lungs
      during partial liquid ventilation (PLV). MATERIALS AND METHODS: Supine chest
      radiographs (391 anteroposterior, 154 lateral radiographs) were obtained before
      and after daily perflubron instillation in 13 adults undergoing PLV who were
      receiving extracorporeal life support. Perflubron distribution, barotrauma, and
      inability to discern catheters were evaluated. RESULTS: Immediately after
      instillation of perflubron, opacification of more than two-thirds of the lungs
      was shown in 12 of 13 patients. A gravity-dependent distribution of perflubron
      was shown on 146 (95%) of 154 lateral radiographs. Perflubron gradually cleared
      until it filled less than one-third of the lungs 6.8 days later (range, 2-20
      days). In the five survivors, minimal perflubron was visible up to 138 days. In
      five patients, perflubron increased the visibility of small pneumothoraces
      present before PLV. Location of intrathoracic catheters was obscured on 44
      radiographs. CONCLUSION: Perflubron symmetrically opacifies the lungs in a
      gravity-dependent distribution during PLV and clears to minimal levels within 3
      weeks.

PMID- 8539367
TI  - Stent-grafts for endovascular treatment of abdominal aortic aneurysms: how much
      do we really know?

PMID- 8539368
TI  - Juxtaphrenic peak in upper and middle lobe volume loss: assessment with CT.
AB  - PURPOSE: To investigate the anatomic basis for the juxtaphrenic peak (JP) in
      upper and/or middle lobe volume loss through radiographic and computed
      tomographic (CT) correlation. MATERIALS AND METHODS: Chest radiographs and CT
      scans were reviewed in 32 patients with upper or middle lobe volume loss. The
      study included 33 cases of volume loss: 12 affected the left upper lobe; 12, the
      right upper lobe; five, the right upper and middle lobes; and four, the middle
      lobe. JPs and linear opacities identified on chest radiographs were correlated
      with juxtadiaphragmatic structures on CT scans. RESULTS: A JP was identified in
      22 of 33 (67%) cases, including nine of 12 (75%) with left upper lobe volume loss
      and eight of 12 (67%) with right upper lobe, four of five (80%) with combined
      upper and middle lobe, and one of four (25%) with middle lobe volume loss. The JP
      was due to an inferior accessory fissure in 14 of 22 (64%) cases. Other causes
      included a medial septum and an accessory fissure other than the inferior
      accessory fissure. CONCLUSION: The JP sign is seen in the majority of cases with
      upper lobe or combined upper and middle lobe volume loss. The sign is most
      commonly related to an inferior accessory fissure.

PMID- 8539369
TI  - Laryngeal carcinoma after radiation therapy: correlation of abnormal MR imaging
      signal patterns in laryngeal cartilage with the risk of recurrence.
AB  - PURPOSE: To correlate abnormal magnetic resonance (MR) imaging signal patterns in
      cartilage with the effectiveness of radiation treatment. MATERIALS AND METHODS:
      Eighty previously untreated patients underwent MR imaging and radiation therapy
      with a curative intent. Cartilage was considered to have an abnormal signal
      pattern if it had intermediate signal intensity on T1-weighted spin-echo (SE) MR
      images and high signal intensity on T2-weighted SE MR images. The minimum follow
      up was 2 years. RESULTS: Abnormal MR imaging signal patterns of the thyroid
      cartilage (P < .001; P < .04) were more ominous than those of other cartilage.
      Abnormal signal patterns in cartilage of patients with small tumors (< 5 cm3 and
      especially < 1 cm3) were less significant. Abnormal signal patterns in cartilage
      combined with a large tumor (> 5 cm3) worsened the prognosis significantly (P <
      .05). CONCLUSION: Abnormal MR imaging signal patterns in cartilage may not
      indicate a poor prognosis in every case. Abnormal signal intensity in the thyroid
      cartilage combined with a tumor volume of > 5 cm3, however, appears to indicate
      an adverse prognosis with regard to tumor recurrence.

PMID- 8539370
TI  - Squamous cell carcinomas that arise in the oral cavity and tongue base: can CT
      help predict perineural or vascular invasion?
AB  - PURPOSE: To determine the ability to use computed tomography (CT) to predict
      invasion of adjacent nerves or vessels by oral cavity tumors. MATERIALS AND
      METHODS: Contrast material-enhanced CT scans and histopathologic reports were
      retrospectively reviewed in 48 patients (36 men, 12 women) aged 38-75 years who
      underwent gross total resection of squamous cell carcinomas arising in the
      tongue, the base of the tongue, and the floor of the mouth. CT criteria for
      diagnosis of perineural or vascular invasion were aggressive tumor margins,
      invasion of the sublingual space, and direct adjacency of the tumor to the
      enhanced lingual vasculature in the sublingual space. CT and histopathologic
      findings of perineural and/or vascular invasion by tumor were correlated in all
      patients. RESULTS: With the above criteria, CT findings predictive of perineural
      or vascular invasion had a sensitivity of 88%; specificity, 83%; positive
      predictive value, 85%; and negative predictive value, 84%. CONCLUSION: CT
      findings can be used to predict perineural or vascular invasion by oral cavity
      tumors.

PMID- 8539371
TI  - Cerebral CT venography.
AB  - PURPOSE: To produce cerebral venograms with thin-section helical computed
      tomography (CT) and to assess their diagnostic utility. MATERIALS AND METHODS:
      Thirty-six CT venograms were obtained in 33 patients after intravenous
      administration of iodinated contrast material. Eighteen patients had suspected
      dural sinus thrombosis. Twelve patients had tumor adjacent to a major venous
      structure. Three patients underwent CT venography during CT angiography. RESULTS:
      Superior sagittal, transverse, and straight sinuses were identified on every CT
      venogram. Other veins were seen with high frequency. Dural sinus thrombosis was
      diagnosed in seven patients, with magnetic resonance (MR) venographic correlation
      in five patients. CT venograms were easier to interpret and had fewer artifacts
      than MR venograms. Relationships of tumor to adjacent cerebral venous structures
      were well shown on CT venograms. CONCLUSION: CT venography yields detailed images
      of the intracranial venous circulation with consistently high quality. It is a
      rapid, useful method for diagnosis of dural sinus thrombosis and for preoperative
      mapping of venous structures in patients with neoplasm.

PMID- 8539372
TI  - Resuscitation and radiology.

PMID- 8539373
TI  - Intracranial calcification on gradient-echo phase image: depiction of diamagnetic
      susceptibility.
AB  - PURPOSE: To differentiate calcification from hemorrhage on the basis of
      susceptibility at magnetic resonance imaging. MATERIALS AND METHODS: Gradient
      recalled echo (GRE) phase imaging was performed at 1.5 T in 101 calcified areas
      (15 in the basal ganglia, 86 out of the basal ganglia) and 39 uncalcified
      locations (13 choroid plexus and pineal glands, 26 old hemorrhages). Experiments
      with a small lead particle and a numerical simulation were also performed.
      RESULTS: The majority of calcifications outside the basal ganglia (n = 63)
      revealed a phase shift that represents diamagnetic susceptibility and was similar
      to the phase shift in the lead particle and to the calculated phase shift for a
      diamagnetic sphere. All hemorrhages and almost all calcified basal ganglia
      revealed a phase shift that represents paramagnetic susceptibility. All
      uncalcified choroid plexus and pineal glands revealed no obvious phase shift. Any
      location without calcification did not reveal the diamagnetic phase shift.
      CONCLUSION: GRE phase imaging differentiated paramagnetic from diamagnetic
      susceptibility, which was specific for calcification.

PMID- 8539374
TI  - Cerebral vasospastic vessels: histologic changes after percutaneous transluminal
      angioplasty.
AB  - PURPOSE: To investigate histologic changes before and after percutaneous
      transluminal angioplasty (PTA) in experimental cerebral vasospasm in comparison
      with normal vessels. MATERIALS AND METHODS: In seven monkeys, vasospasm was
      induced in the subarachnoid space. After 7 days, PTA was performed. Microscopic
      studies were performed in vasospastic vessels. In two animals, vasospasm was
      induced but angioplasty was not performed. The controls were two animals without
      vasospasm who underwent only contralateral angioplasty. RESULTS: Angiography
      after vasospasm revealed marked narrowing but dilatation after PTA, without
      changes in distal spastic vessels. Specimens after PTA showed platelets that
      covered denuded endothelium, stretching, and focal dehiscence of internal elastic
      lamina and altered myocytes in media. Myocytes were deformed and arranged
      irregularly. These changes were not uniform. CONCLUSION: The prolonged effect of
      PTA may be caused by mechanical damage of myocytes and the nonuniformity of
      histologic changes in vascular walls.

PMID- 8539375
TI  - Early-stage rheumatoid arthritis: diagnostic accuracy of MR imaging.
AB  - PURPOSE: To investigate the role of magnetic resonance (MR) imaging in diagnosing
      early rheumatoid arthritis (RA). MATERIALS AND METHODS: Twenty patients (three
      men, 17 women; age range, 21-72 years) with clinically and radiologically proved
      RA underwent evaluation to define an MR imaging criterion for diagnosing synovial
      inflammation due to RA. Twenty-seven patients (16 with RA, 11 without RA [control
      patients]; three men, 24 women; age range, 19-75 years) suspected to have early
      RA but without radiographic abnormalities underwent evaluation to test the
      accuracy of using the criterion to diagnose RA. In each patient, coronal, fat
      suppressed, and gadolinium contrast material-enhanced, T1-weighted images of both
      hands were obtained. RESULTS: The MR imaging criterion was periarticular contrast
      material enhancement of the wrists or the metacarpophalangeal and/or proximal
      interphalangeal joints in both hands. In the diagnosis of early RA, sensitivity
      and negative predictive value were both 100%, specificity was 73%, and accuracy
      was 89%. CONCLUSION: MR imaging is extremely useful in diagnosing early RA.

PMID- 8539376
TI  - Complications after emergency tube thoracostomy: assessment with CT.

PMID- 8539377
TI  - Sternoclavicular joint: MR imaging--anatomic correlation.
AB  - PURPOSE: To correlate magnetic resonance (MR) images of the sternoclavicular
      joint with anatomic sections. MATERIALS AND METHODS: MR imaging was performed on
      14 sternoclavicular joints in seven specimens from cadavers (three men and four
      women 64-94 years of age at death; mean, 84 years). MR arthrography was performed
      in four specimens (eight joints), after injection of gadopentetate dimeglumine.
      After imaging, the specimens were frozen and cut into 3-mm-thick slices along the
      MR imaging planes. Images were correlated with the anatomic slices. RESULTS: MR
      imaging depicted the anatomy of the sternoclavicular joint and surrounding soft
      tissue. T2-weighted and proton-density-weighted images were superior to T1
      weighted images in depiction of the intraarticular disk. MR arthrography depicted
      best the intraarticular disk and four of five perforations and delineated the
      joint capsule. All perforations also were depicted on T2-weighted images.
      CONCLUSION: MR imaging allows delineation of all structures of the
      sternoclavicular joint. MR arthrography allows delineation of perforations of the
      intraarticular disk.

PMID- 8539378
TI  - Posterolateral aspect of the knee: improved MR imaging with a coronal oblique
      technique.
AB  - PURPOSE: To determine if angling the coronal plane in magnetic resonance (MR)
      imaging of the knee increases the conspicuity of the posterolateral structures.
      MATERIALS AND METHODS: A coronal oblique MR imaging sequence performed parallel
      to the popliteal tendon proximally was added to our routine study in patient knee
      examinations. One hundred patients (age range, 12-72 years) underwent MR imaging.
      RESULTS: Coronal oblique images depicted the arcuate ligament in 46%, the
      fabellofibular ligament in 48%, and the fibular origin of the popliteal muscle in
      53% of the patients, whereas standard coronal images depicted these in 10%, 34%,
      and 8% of the patients, respectively. Sagittal oblique images did not adequately
      depict these structures. CONCLUSION: Depiction of the structures in the
      posterolateral aspect of the knee was optimal on coronal oblique images. We
      advocate obtaining coronal oblique T2-weighted images in patients with either
      posterolateral knee pain or suspected injury to the posterolateral ligamentous
      structures.

PMID- 8539379
TI  - Lateral-compartment bone contusions in adolescents with intact anterior cruciate
      ligaments.
AB  - PURPOSE: To determine how often lateral-compartment bone contusions are seen on
      magnetic resonance (MR) images of knees in adolescents with intact anterior
      cruciate ligaments (ACLs). MATERIALS AND METHODS: MR images obtained in 53
      adolescent patients (30 male, 23 female; aged 10-20 years) were reviewed to
      detect bone contusions in the posterolateral tibial plateau or the lateral
      femoral condyle. ACLs were also evaluated with accepted criteria for the
      diagnosis of ligamental disruption. Only patients referred for evaluation of a
      knee injury or mechanical symptoms were included. RESULTS: Five patients with
      bone contusions had an intact ACL at MR imaging. One of the five had arthroscopic
      confirmation. Fifteen other patients had complete ACL disruptions: 13 of these
      patients had typical bone contusions; the other two had no bone abnormalities but
      had chronic ACL tears. Thus, 28% of the 18 patients with typical bone contusions
      had intact ACLs. CONCLUSION: Adolescents may have the same pattern of contusions
      as adults but may maintain an intact ACL owing to increased ligamentous laxity.

PMID- 8539380
TI  - Accuracy of fat-suppressed three-dimensional spoiled gradient-echo FLASH MR
      imaging in the detection of patellofemoral articular cartilage abnormalities.
AB  - PURPOSE: To determine the accuracy of T1-weighted fat-suppressed (FS) three
      dimensional (3D) fast low-angle shot (FLASH) magnetic resonance (MR) imaging for
      the detection of articular cartilage abnormalities of the patellofemoral joint.
      MATERIALS AND METHODS: Forty-one patients with suspected internal derangement of
      the knee were examined with a T1-weighted FS 3D FLASH sequence and subsequently
      underwent arthroscopy. The patellofemoral articular cartilage was graded blindly
      on both the MR and arthroscopic images with a modification of the Noyes
      classification scheme. RESULTS: For the detection of abnormal articular cartilage
      of the patellofemoral joint with the FS 3D FLASH sequence, sensitivity was 81%,
      specificity was 97%, and accuracy was 97%. Of the lesions detected on MR images,
      77% were graded identically on MR and arthroscopic images. For the remaining 23%,
      MR imaging and arthroscopic ratings were within one grade of each other.
      CONCLUSION: T1-weighted FS 3D FLASH imaging is accurate for the detection and
      grading of articular cartilage abnormalities of the patellofemoral joint.

PMID- 8539381
TI  - "Do not resuscitate" orders in the radiology department: an interpretation.

PMID- 8539382
TI  - Distal radius: in vivo assessment with quantitative MR imaging, peripheral
      quantitative CT, and dual X-ray absorptiometry.
AB  - PURPOSE: To evaluate in vivo the relationship between magnetic resonance (MR)
      imaging relaxation time and bone mineral density (BMD) at the distal radius.
      MATERIALS AND METHODS: The 1/T2* MR imaging relaxation rates and dual X-ray
      absorptiometry (DXA) measurements were evaluated in the trabecular bone of the
      distal 5 cm of the radius in 14 healthy premenopausal women and 11 healthy
      postmenopausal women and in 11 women with osteoporosis. Trabecular and total BMD
      were measured with peripheral quantitative computed tomography (CT). RESULTS: In
      healthy women, 1/T2* values and trabecular BMD at peripheral quantitative CT were
      significantly correlated but 1/T2* and total BMD were not. Statistically
      significant (P = .03) correlations between 1/T2* and DXA were found only in the
      most distal area covered with DXA. The 1/T2* values were more closely correlated
      with age and showed higher relative annual decreases (0.47%-0.81%) than
      peripheral quantitative CT (0.20%-0.59%) or DXA (0.10%-0.39%). Pre- and
      postmenopausal healthy subjects could be distinguished only with MR imaging, and
      postmenopausal healthy and osteoporotic subjects only with CT and DXA.
      CONCLUSION: MR imaging relaxation rates correlate well with trabecular BMD in
      vivo.

PMID- 8539383
TI  - Complications of flexor tendon repair in the hand: MR imaging assessment.
AB  - PURPOSE: To determine if magnetic resonance (MR) imaging enables differentiation
      of adhesions from tendon rupture after repair of digital flexor tendon injuries.
      MATERIALS AND METHODS: The reference group comprised eight tendon sutures with a
      good clinical outcome. Axial and sagittal spin-echo sequences and three
      dimensional gradient-echo sequences with curved reconstructions were analyzed in
      63 injured fingers. Reoperation was performed in 41 fingers. RESULTS: MR imaging
      depicted isolated peritendinous adhesions (n = 31), most often with a continuous,
      uniform tendon (sensitivity 91%, specificity 100%). There were two types of
      rupture: frank rupture (n = 140; sensitivity 100%, specificity 100%) or elongated
      callus (n = 18; sensitivity 100%, specificity 94%). Tendon gap was significantly
      longer in frank rupture (P = .0011). Thin fibrous continuity existed with
      elongated callus. Tenolysis was sufficient when the callus was short and mature
      with predominant new collagen fibers. Axial spin-echo sections were essential, as
      they showed the maturation of the callus. CONCLUSION: MR imaging may enable
      distinction among several complications that occur after repair of an injured
      digital flexor tendon.

PMID- 8539384
TI  - Detection of malignancies with SPECT versus PET, with 2-[fluorine-18]fluoro-2
      deoxy-D-glucose.
AB  - PURPOSE: To compare single photon emission computed tomography (SPECT) with 2
      [fluorine-18]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography
      (PET) with FDG to evaluate malignancies. MATERIALS AND METHODS: PET and SPECT,
      with fluorine-18 sodium fluoride, were performed sequentially in a cylindric
      phantom that contained different size spheres with activity ratios of 5:1, 10:1,
      and 15:1. PET and SPECT were also performed in 24 patients with known or
      suspected malignancies. RESULTS: Sensitivities of PET and SPECT were 2,238
      cpm/microCi (82.8 cpm/MBq) and 129 cpm/microCi (4.8 cpm/MBq), respectively
      (reconstructed spatial resolution, 7 and 17 mm, respectively [13-cm radius of
      rotation]). In the phantom studies, lesions of 1.5 and 1.3 cm or more in diameter
      were detected with a ratio of 5:1 and 10:1, respectively, and an information
      density of 150 counts per square centimeter. At FDG PET, 46 hypermetabolic
      lesions consistent with tumor were depicted in patients; at FDG SPECT, 36 (78%)
      were depicted. Sensitivity of FDG SPECT was 92% for detection of malignancies 1.8
      cm or more in diameter seen at FDG PET. CONCLUSION: Findings at FDG SPECT can
      help differentiate benign from malignant lesions.

PMID- 8539385
TI  - Recurrent hepatocellular carcinoma after liver transplantation: spectrum of CT
      findings and recurrence patterns.
AB  - PURPOSE: To correlate computed tomographic (CT) and serum tumor marker (alpha
      fetoprotein [AFP] and des-gamma-carboxy-prothrombin [DGCP]) findings in recurrent
      hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT).
      MATERIALS AND METHODS: At retrospective review of the cases in 124 patients, CT
      findings were recorded by consensus of at least two nonblinded observers and
      compared with levels of AFP and DGCP. RESULTS: In 35 patients (68 sites), CT
      depicted recurrent HCC (most frequently in lungs [n = 18] and liver allograft [n
      = 16]) in a single site in 19 patients (54%) and in more than one site in 16
      patients (46%). No stage I or II HCC recurred after 18-78 months (mean
      recurrence, 39 months). Stage IVA HCC recurred four times as often as stage III
      HCC (P < .001). Abnormally high serum AFP and DGCP levels indicated 69% and 43%,
      respectively, in patients with recurrent disease. CONCLUSION: HCC recurrence
      after OLT correlates with initial stage, and CT is more sensitive than serum
      tumor markers in its detection.

PMID- 8539386
TI  - Liver necrosis and regeneration after fulminant hepatitis: pathologic correlation
      with CT and MR findings.
AB  - PURPOSE: To characterize computed tomographic (CT) and magnetic resonance (MR)
      findings of liver necrosis and regeneration after fulminant hepatitis. MATERIALS
      AND METHODS: Three patients with fulminant hepatitis underwent CT before
      orthotopic liver transplantation; one also underwent MR imaging. These findings
      were retrospectively reviewed and compared with gross and histologic findings
      obtained after transplantation. RESULTS: Regions of liver necrosis demonstrated
      low attenuation on CT scans before contrast material was administered and
      enhanced to attenuation equal to or greater than that of liver regeneration on
      postcontrast CT images. Conversely, nodular liver regeneration demonstrated
      hyperattenuation on precontrast and hypoattenuation on postcontrast CT images,
      which simulated neoplastic lesions. The necrotic liver parenchyma was seen as
      high and low intensity on T2- and T1-weighted MR images, respectively, whereas
      areas of regeneration appeared as hypo- and hyperintense. CONCLUSION:
      Characteristic patterns of liver regeneration after fulminant hepatitis may be
      seen at CT and MR imaging. Recognition of this regeneration process may avoid an
      incorrect diagnosis of malignancy.

PMID- 8539387
TI  - Biliary stones and sludge in liver transplant patients: a 13-year experience.
AB  - PURPOSE: To determine the prevalence, radiologic features, and clinical
      significance of bile duct filling defects (BDFDs) in liver transplant recipients
      studied with cholangiography. MATERIALS AND METHODS: During 13 years, 4,100
      cholangiograms were obtained in 1,650 patients. All studies showing BDFD
      suggestive of stones, sludge, cast, or necrotic debris were retrospectively
      evaluated. RESULTS: The prevalence of BDFD was 5.7% (n = 94). On the basis of
      cholangiographic appearance, BDFDs were categorized as sludge or cast in 53
      grafts (56%), stones in 32 (34%), and necrotic debris in nine (10%). Forty-three
      patients (46%) underwent surgical biliary reconstruction, while 14 (15%)
      underwent interventional radiologic treatments. Twenty-four of 32 stones (75%)
      were treated with surgical reconstruction, compared with 31% (19 of 62 grafts) of
      other BDFDs (P < .0001). Necrotic debris and sludge were associated with hepatic
      artery occlusion in seven of nine (78%) and 16 of 53 (30%) grafts, respectively.
      CONCLUSION: Stones and sludge are relatively infrequent after liver
      transplantation but are associated with high morbidity. Surgical or
      interventional radiologic treatments are usually performed. Bile duct stones are
      usually treated with surgical biliary reconstruction. While debris and bile duct
      necrosis are due to ischemia from hepatic artery occlusion, sludge may also have
      an ischemic pathogenesis in some cases.

PMID- 8539388
TI  - Intraductal mucin-producing tumors of the pancreas: imaging findings.
AB  - PURPOSE: To evaluate the radiologic characteristics of intraductal mucin
      producing tumors of the pancreas. MATERIALS AND METHODS: Sixteen patients with
      intraductal tumors underwent ultrasound (US); (n = 15), computed tomography (CT);
      (n = 16), endoscopic retrograde cholangiopancreatography (ERCP); (n = 12), and
      intraoperative pancreatography (n = 2). Findings were compared with those from
      surgery (n = 14) or biopsy (n = 2). RESULTS: Lesions were classified as either
      main duct type or branch duct type tumors. Main duct tumors were characterized at
      US and CT by either diffuse or segmental dilatation of the Wirsung duct.
      Pancreatography showed ductal dilatation and filling defects caused by mucin
      deposits. At US and CT, branch duct tumors, which were mainly located at the
      uncinate process, were seen as fluid-filled masses with central septa and the
      pancreatic duct was dilated. ERCP showed partial or complete opacification of the
      lesion. In four patients, endoscopy showed protrusion of the papilla into the
      duodenal lumen and mucin leaking from its dilated orifice. CONCLUSION: Imaging
      modalities, especially US and ERCP, enable early diagnosis of mucin-producing
      pancreatic tumors.

PMID- 8539390
TI  - Liver hydatid disease: long-term results of percutaneous treatment.
AB  - PURPOSE: To evaluate the long-term effectiveness of percutaneous treatment of
      liver hydatid cysts. MATERIALS AND METHODS: Thirty-one patients (19 female
      patients and 12 male patients; age range, 8-78 years; mean age, 41 years) with 57
      liver hydatid cysts underwent percutaneous treatment. The cysts were treated with
      hypertonic saline (15% NaCl) and/or absolute alcohol. Sonographic and/or
      fluoroscopic guidance was used. RESULTS: Repeated sonography revealed a gradual
      decrease in cyst size. Volume reduction was 18%-99% (mean, 83%). With the
      disappearance of the fluid component, pseudotumor appearance occurred. In all
      treated cases, the cyst wall became irregular and thicker during follow-up. No
      mortality occurred. No abdominal dissemination was encountered during follow-up.
      Major complications were infection of the cavity, hypersensitivity reaction, and
      development of biliary fistula. One cyst recurred 11 months after primary
      drainage. CONCLUSION: Long-term results indicate that percutaneous treatment of
      liver hydatid cysts is an effective and safe method in selected cases.

PMID- 8539389
TI  - Abdominal aortic aneurysms: preliminary technical and clinical results with
      transfemoral placement of endovascular self-expanding stent-grafts.
AB  - PURPOSE: To evaluate treatment of infrarenal abdominal aortic aneurysm (AAA) with
      a new endoluminal stent-graft. MATERIALS AND METHODS: In 26 male patients,
      straight or bifurcated nitinol stents covered with woven Dacron graft material
      were implanted to treat eccentric saccular AAA (n = 3) or AAA involving the
      bifurcation and common iliac arteries (n = 23), with follow-up from 8 days to 8
      1/2 months. RESULTS: Implantation was technically successful in all but one of
      the 26 (96%) patients (leak of the stent-graft for more than 3 months
      necessitated implantation of an additional covered stent). In seven of the 26
      patients, minor residual perfusion persisted immediately after implantation, but
      complete thrombosis occurred within 7 days. Five procedure-related complications
      occurred: distal embolization (n = 2); local hematoma, which necessitated surgery
      (n = 1); acute hepatic failure due to gastric bleeding, in a patient with liver
      cirrhosis (n = 1); and stent-graft occlusion due to emboli originating from the
      left atrium (n = 1). CONCLUSION: Exclusion of AAA from circulation was feasible,
      safe, and clinically effective with the new stent-graft.

PMID- 8539391
TI  - Benign adenomatous kidney neoplasms in children with polycythemia: imaging
      findings.
AB  - PURPOSE: To correlate pathologic, computed tomographic (CT), and ultrasound (US)
      characteristics of nephrogenic adenofibromas and embryonal adenomas (uncommon
      pediatric renal tumors) in children. MATERIALS AND METHODS: Medical records and
      imaging and pathologic findings were reviewed in three children (aged 6 1/2, 7,
      and 11 years) with adenomatous renal tumors and polycythemia. Specimens were
      reviewed at the National Wilms Tumor Study Pathology Center (Loma Linda, Calif).
      RESULTS: All tumors were smaller than 3 cm in greatest dimension. They were
      hyperechoic on US scans and had high attenuation on unenhanced CT scans. Two
      patients underwent nephrectomy for initial diagnosis of Wilms tumor. The third
      underwent local excision. At pathologic examination, embryonal-appearing
      adenomatous epithelial cells were found to form tubules and papillae with
      abundant psammomatous calcifications. Two masses were classified as embryonal
      adenomas and one as nephrogenic adenofibroma. CONCLUSION: Increased attenuation
      on CT scans and increased echogenicity on US scans of renal adenomatous tumors
      are distinctive findings that may reflect the presence of tubulopapillary
      structures and psammomatous calcifications.

PMID- 8539392
TI  - Functional bladder capacity measured during radionuclide cystography in children.
AB  - PURPOSE: To estimate functional bladder capacity (FBC) during direct radionuclide
      cystography and to assess the relationship between vesicoureteral reflux and FBC.
      MATERIALS AND METHODS: By using 5,165 direct radionuclide cystograms in patients
      aged newborn to 14 years, linear and nonlinear models were fit to estimate FBC
      from age. Analysis was performed on girls and boys separately. In a subgroup,
      height and weight were evaluated as predictors of FBC. Linear models were used to
      assess differences in predicted FBC according to sex and reflux status. RESULTS:
      The relationship between FBC and age is best described by a nonlinear power
      function. Percentiles derived from this model are close to the empiric
      percentiles of FBC. When controlling for age, girls and patients with reflux had
      larger bladder capacities (P < .01). Height and weight did not improve FBC
      prediction accuracy. CONCLUSION: FBC follows a curve with increasing age. The
      nonlinear relationship between FBC and age appears to be consistent with
      maturation in infants and children.

PMID- 8539393
TI  - Patterns of contrast enhancement in the pediatric spine at MR imaging with single
      and triple-dose gadolinium.
AB  - PURPOSE: To assess patterns of nerve root and spinal cord contrast enhancement in
      the pediatric spine at magnetic resonance (MR) imaging with single- and triple
      dose gadolinium. MATERIALS AND METHODS: In three control patients with no
      suspected pathologic spinal condition and 19 patients with a suspected condition,
      spinal cords were evaluated prospectively for potential spread of tumor to
      cerebrospinal fluid ("drop metastases") (n = 18) or Guillain-Barre syndrome (n =
      1). After enhancement with 0.1 mmol/kg gadolinium, patients without definite drop
      metastases (n = 8) received a booster of 0.2 mmol/kg gadolinium 30-40 minutes
      later; clinical follow-up was obtained 12 1/2 to 19 months later. RESULTS: Drop
      metastases appeared as nodular areas of enhancement in 11 patients. Vascular
      enhancement related to the spinal cord surface and emerging nerve roots was
      observed in images obtained in all control patients, as well as in patients with
      negative findings at lumbar puncture and at clinical or MR imaging follow-up
      examination (n = 6). Vascular and nerve root enhancement increased with triple
      dose gadolinium and was greater in patients after radiation therapy (n = 17) than
      in control patients (n = 3). CONCLUSION: Use of triple-dose gadolinium did not
      result in detection of additional cases of drop metastases.

PMID- 8539394
TI  - Early-stage breast cancer: arm edema after wide excision and breast irradiation.
AB  - PURPOSE: To determine the incidence of arm edema in women with early-stage breast
      cancer after breast-conserving surgery and irradiation. MATERIALS AND METHODS:
      Women aged 29-83 years (mean, 55.9 years) treated with breast-conserving surgery
      and irradiation (n = 183) underwent a series of measurements of the circumference
      of each arm. Patient and treatment factors were analyzed for predictive value.
      RESULTS: Arm edema developed in 35.0% (n = 64), and clinically significant edema
      developed in 17.5% (n = 32) of patients. Dissections that yielded 16 or more
      nodes led to a 44% actuarial incidence of edema and a 29% actuarial incidence of
      clinically significant edema. Clinically significant arm changes occurred in 19
      of the 87 (22%) women older than 55 years and in 13 of the 96 (14%) women younger
      than 55 years (P = .002). Chemotherapy, breast radiation dose, and use of
      tamoxifen had no effect on development of edema. CONCLUSION: Axillary dissection
      producing more than 15 nodes and age older than 55 years are predictive of arm
      edema.

PMID- 8539395
TI  - Hepatocellular carcinoma: detection with double-phase helical CT during arterial
      portography.
AB  - Retrospective analysis of findings at double-phase helical computed tomography
      (CT) during arterial portography was performed in 42 hepatocellular carcinomas
      (HCCs) in 31 patients. Phase 1 scanning started 30-35 seconds after the beginning
      of injection of contrast material; phase 2 scanning started 10-18 seconds after
      the end of phase 1. The overall detection rate for HCCs was 83% (35 of 42) in
      phase 1, 81% (34 of 42) in phase 2, and 90% (38 of 42) for combined phase 1 and 2
      findings.

PMID- 8539396
TI  - Stereoscopically guided characterization of three-dimensional dynamic MR images
      of the breast.
AB  - A workstation was used to postprocess volume-rendered three-dimensional (3D)
      dynamic contrast material-enhanced magnetic resonance (MR) images of a breast
      carcinoma and a breast adenoma. Use of a 3D cursor allowed stereoscopic
      interactive probing of specific voxels to quantify contrast enhancement over
      time, which was mapped to a gray scale that effectively displayed enhancement as
      a fourth dimension. This technique is generally applicable to any time-dependent
      3D imaging modality.

PMID- 8539397
TI  - Academy of radiology research begins operations.

PMID- 8539398
TI  - Accuracy of fat-suppressed MR imaging of the shoulder for detection of partial
      thickness rotator cuff tears.

PMID- 8539399
TI  - Percutaneous, radiographically guided biopsy: a history.

PMID- 8539400
TI  - The RSNA Electronic Journal: RSNA EJ.

PMID- 8539401
TI  - Hepatic tumors: predisposing factors for complications of transcatheter oily
      chemoembolization.
AB  - PURPOSE: To elucidate major complications and their predisposing factors in
      transcatheter oily chemoembolization (TOCE) for hepatic tumors. MATERIALS AND
      METHODS: In a retrospective study of 351 patients (aged 26-82 years) with hepatic
      tumors, TOCE was performed 942 times with an emulsion of iodized oil (3-40 mL)
      and doxorubicin hydrochloride (20-60 mg). In 126 patients, TOCE was followed by
      absorbable gelatin sponge embolization. RESULTS: Complications were severe
      postembolization syndrome (n = 53); hepatic insufficiency (n = 20), infarction (n
      = 1), or abscess (n = 1); intrahepatic biloma formation (n = 3); tumor rupture (n
      = 3); septicemia (n = 9); coagulopathy (n = 1); gastrointestinal bleeding (n =
      10); gallbladder (n = 5) or splenic infarction (n = 4); pulmonary oil embolism (n
      = 6); and spinal cord injury (n = 1). Important predisposing factors were major
      portal vein obstruction, compromised hepatic functional reserve, biliary
      obstruction, previous biliary surgery, excessive amount (> 20 mL) of iodized oil,
      hepatic arterial occlusion after repeated TOCE, and nonselective embolization.
      CONCLUSION: Most patients with major complications after TOCE had preexisting
      risk factors.

PMID- 8539402
TI  - Fibrin sleeve stripping for salvage of failing hemodialysis catheters: technique
      and initial results.
AB  - PURPOSE: To evaluate percutaneous fibrin sleeve stripping (PFSS) to prolong
      functional patency in failing hemodialysis catheters. MATERIALS AND METHODS:
      Forty PFSS procedures were performed in 24 catheters in 23 consecutive patients
      with an inadequate blood flow rate (< 200 mL/min) during hemodialysis. The fibrin
      sleeve was mechanically stripped off the shaft of the catheter with a snare
      introduced via the common femoral vein. Durability of PFSS was determined with
      life-table analysis. RESULTS: Median time from catheter placement to initial
      failure was 3.5 months (range, 5 days to 22 months). The technical success rate
      for PFSS was 100%; initial patency was restored in 39 of 40 procedures (98%), and
      no symptomatic pulmonary embolism occurred. Primary patency after single PFSS was
      45% at 3 months and 28% at 6 months (median added patency, 2.8 months).
      Postprocedure secondary patency with multiple PFSS procedures was 83% at 3 months
      and 72% at 6 months (P = .01) (overall catheter patency, 90% at 6 months and 81%
      at 1 year [P < .001]). CONCLUSION: Multiple PFSS procedures can prolong patency
      in hemodialysis catheters with a fibrin sleeve.

PMID- 8539403
TI  - Aortic and iliac stenoses: follow-up results of stent placement after
      insufficient balloon angioplasty in 118 cases.
AB  - PURPOSE: To demonstrate follow-up results of stent placement in aortic and iliac
      stenoses. MATERIALS AND METHODS: A total of 109 patients with 118 aortoiliac
      stenoses underwent placement of self-expanding stents. Mean length of the
      stenotic segments was 3 cm +/- 2 (standard deviation). Mean ankle-arm index at
      rest was 0.58 +/- 0.2. A total of 101 patients were followed up angiographically
      or clinically. RESULTS: A mean of 1.2 stents +/- 0.5 were inserted per case.
      Clinical stage improved in 112 cases; it improved two or more stages in 89 cases.
      Mean ankle-arm index improved to 0.92 +/- 0.17. Total and major complication
      rates were 6.8% and 3.4%, respectively. Subacute occlusion occurred in four
      patients. Late stent obstruction occurred after a mean of 27 months (range, 16-48
      months) in 10 cases. Primary patency was 95% after 1 year and 88% after 2 years;
      4-year patency was 82%. Secondary patency was 96% after 1 year and 93% after 2
      years. Three- and 4-year secondary patency were both 91%. CONCLUSION: Placement
      of self-expanding stents in iliac stenoses is technically safe and offers
      sufficient follow-up patency.

PMID- 8539404
TI  - The ABCs of radiology.

PMID- 8539405
TI  - Arterial thrombosis below the inguinal ligament: percutaneous treatment with a
      thrombosuction catheter.
AB  - PURPOSE: To assess the safety and clinical efficacy of using a thrombosuction
      catheter for treatment of arterial thrombosis below the inguinal ligament.
      MATERIALS AND METHODS: The catheter was used in a consecutive group of 28
      patients (10 women, 18 men; age range, 38-87 years; mean age, 66.7 years; with 11
      native vessels and 17 grafts) with acute infrainguinal thrombosis. Initial local
      success, clinical success, and 30-day outcome were studied. RESULTS: The initial
      local success rate was 82%. The clinical success rate was 73% for native vessels
      and 53% for grafts. The 30-day success rate was 73% for native vessels and 35%
      for grafts. Displacement of thrombotic material during the procedure resulted in
      a clinical complication in one patient. There were no bleeding complications. In
      58% of all patients (n = 26), no lytic drug was used. CONCLUSION: The
      thrombosuction catheter seems to be a safe, fast-acting alternative or supplement
      to local lysis therapy for infrainguinal arterial thrombosis.

PMID- 8539406
TI  - Navigator-echo-based real-time respiratory gating and triggering for reduction of
      respiration effects in three-dimensional coronary MR angiography.
AB  - PURPOSE: To test the hypothesis that respiration effects in three-dimensional
      (3D) coronary magnetic resonance (MR) imaging can be reduced with navigator-echo
      based gating or triggering according to the superior-inferior position of the
      diaphragm. MATERIALS AND METHODS: Real-time respiratory gating and respiratory
      triggering (breath hold with feedback) were implemented with navigator echoes in
      a magnetization-prepared, segmented, 3D coronary imaging sequence. The two
      techniques were first tested with a motion phantom. An imaging protocol that
      compared real-time respiratory-gated acquisition, real-time respiratory-triggered
      acquisition, and continuous acquisition was then evaluated in six healthy
      subjects. RESULTS: Real-time respiratory-gated and respiratory-triggered
      acquisition were superior to continuous acquisition with two signals averaged (P
      = .025). The performance of the gated acquisition was about the same as that of
      the triggered acquisition (P = .05). CONCLUSION: Navigator-echo-based, real-time
      respiratory-gating and respiratory-triggering techniques are practical methods
      for effective reduction of respiration effects in coronary MR imaging.

PMID- 8539407
TI  - Pulmonary angiography performed with iopamidol: complications in 1,434 patients.
AB  - PURPOSE: To evaluate the safety of pulmonary angiography performed with iopamidol
      compared with pulmonary angiography performed with ionic contrast media.
      MATERIALS AND METHODS: The data in 1,434 patients who underwent pulmonary
      angiography with iopamidol 76% were retrospectively reviewed. Complications that
      occurred within 48 hours were identified with review of hospital charts and/or
      computer records. RESULTS: Pulmonary arterial hypertension was present in 402
      patients and was severe in 99. Pulmonary embolus was diagnosed in 357 patients
      (24.9%). Major complications occurred in four patients (0.3%). Respiratory
      insufficiency occurred in two of these patients. Catheterization was not
      completed in two patients due to catheter-induced cardiac arrhythmia that was
      refractory to treatment. No procedure-related deaths occurred. During the
      periprocedural period, eight patients required intubation and 10 patients died;
      all patients previously were critically ill. CONCLUSION: Pulmonary angiography is
      a safe procedure, and the margin of safety is enhanced by the use of iopamidol.

PMID- 8539408
TI  - Symptomatic deep vein thrombosis: diagnosis with limited compression US.
AB  - PURPOSE: To evaluate the utility of limited compression ultrasound (US) in the
      diagnosis of deep vein thrombosis (DVT). MATERIALS AND METHODS: Positive
      sonograms (n = 160) in 155 symptomatic patients were reviewed retrospectively to
      assess the distribution of DVT. Fifty-three symptomatic patients underwent 56
      limited US examinations of the common femoral and popliteal veins only, followed
      by traditional US of the entire venous system of the lower extremity from the
      inguinal ligament to the calf veins. RESULTS: Proximal vein thrombosis was seen
      in 146 cases (91%); the other 14 cases (9%) showed isolated calf vein thrombosis.
      In 145 cases (99%), either the common femoral or the popliteal vein was involved.
      Seven (12%) of 56 examinations showed the presence of thrombosis. Limited
      examination depicted each case of DVT that was detected with the complete
      examination, with an average decrease in examination time of 9.7 minutes, or 54%.
      CONCLUSION: Limited compression US in patients with symptomatic DVT is a viable
      alternative to routine US; the examination time is decreased by greater than one
      half.

PMID- 8539409
TI  - Guide-wire entrapment by inferior vena caval filters: in vitro evaluation.
AB  - PURPOSE: To study guide-wire engagement and entrapment by inferior vena caval
      (IVC) filters. MATERIALS AND METHODS: Patterns of engagement were determined in
      six IVC filters with four commonly used guide wires in a simulated IVC. Force
      required to disengage guide wires from filters was measured. RESULTS: Eleven
      engagement patterns were identified with J-tipped guide wires; straight guide
      wires never engaged. The Simon-Nitinol filter engaged guide wires with the
      highest frequency (P < .05). The 15-J wire was engaged most frequently overall (P
      < .0005) but disengaged with forces not significantly different (P > .05) from
      those required to open the J. Entrapment occurred with only the Vena-Tech (VT)
      and 12-F stainless steel Greenfield (12SSG) filters and the 1.5-J and 3-J guide
      wires. The former guide wire became entrapped regardless of engagement pattern;
      the latter became entrapped only when engaged in the hole in the apex of the
      12SSG and VT filters. CONCLUSION: Guide wires with a J tip 3 mm or less in radius
      are at risk for entrapment by the 12SSG and VT filters.

PMID- 8539410
TI  - Metastatic gastrinomas: localization with selective arterial injection of
      secretin.
AB  - PURPOSE: To evaluate localization of hepatic metastases with the intraarterial
      secretin injection test in Zollinger-Ellison syndrome (ZES). MATERIALS AND
      METHODS: Results in 74 patients with ZES (aged 15-70 years) were retrospectively
      studied. All patients had undergone computed tomography (CT), magnetic resonance
      (MR) imaging, ultrasound, abdominal angiography, and an intraarterial secretin
      test, in which venous blood is sampled periodically after injection of secretin.
      RESULTS: Twenty-two patients had liver metastases. An increase in venous gastrin
      concentration of at least 25% at 20 seconds or 50% at 30 seconds after injection
      indicated a positive result. Results were positive in 41% of patients with and 2%
      without liver metastases (P < .0001). Sensitivity of the intraarterial secretin
      test was 41%; of CT and ultrasound, 64%; and of MR imaging and angiography, 77%.
      Intraarterial secretin test results assisted in clinical management in 22% of
      patients. CONCLUSION: With the criteria developed, the intraarterial secretin
      test had high specificity but low sensitivity. It should be used when imaging
      results are unclear.

PMID- 8539411
TI  - Outpatient percutaneous nephrostomy.
AB  - PURPOSE: To assess the feasibility of performing percutaneous nephrostomy (PCN)
      on an outpatient basis in a select group of patients. MATERIALS AND METHODS: In 6
      years, 60 PCN procedures were performed in a subgroup of 48 patients (22 men, 26
      women) carefully selected from a larger group of 881 nephrostomy procedures in
      589 patients. Exclusion criteria included hypertension; untreated urinary tract
      infection, coagulopathy, and staghorn calculi. Indications were calculus (n =
      17), benign stricture (n = 10), and malignant ureteric obstruction (n = 21).
      RESULTS: There was 100% technical success. Six of 48 patients (12%) were admitted
      within a week of PCN; there were no cost savings in these patients. Three of
      these patients (6%) were admitted as a direct consequence of PCN; one had sepsis,
      one had bleeding, and one was unable to manage the PCN tube. Outpatient treatment
      saved the cost of hospitalization in 42 patients (88%). CONCLUSION: Outpatient
      PCN is feasible and safe in carefully selected patients and yields major cost
      savings because it precludes hospital admission.

PMID- 8539412
TI  - Urothelial striations revisited.
AB  - PURPOSE: To confirm that use of low-osmolality contrast media (LOCM) in urography
      increases the frequency with which striations occur in otherwise healthy adults.
      MATERIALS AND METHODS: Two series of urograms obtained in 207 adult patients (101
      men, 106 women) at two institutions after the administration of either LOCM or
      high-osmolality contrast media (HOCM) were reviewed. At the first, 106 patients
      had received LOCM; at the second, 101 had received HOCM. Protocols were similar.
      Urograms were evaluated for the presence and extent of striations. RESULTS: Of
      106 LOCM urograms, 16 (15%) showed striations. Of 101 HOCM urograms, only two
      (2%) showed striations. The difference in striations shown between the two groups
      was significant (P < .002). Striations were most common in renal pelves and
      distal ureters and on radiographs obtained after voiding. CONCLUSION: Detection
      of urothelial striations on LOCM urograms in adults is most often normal.
      Increased prevalence of striations is likely due to decreased urinary tract
      distention associated with LOCM use.

PMID- 8539413
TI  - Nutcracker syndrome: diagnosis with Doppler US.
AB  - PURPOSE: To assess diagnosis of the nutcracker (renal vein entrapment) syndrome
      with Doppler ultrasonography (US). MATERIALS AND METHODS: Doppler US findings in
      16 patients with the nutcracker syndrome and in 18 healthy control subjects were
      compared. The anteroposterior (AP) diameter and peak velocity (PV) were measured
      at the hilar portion of the left renal vein (LRV) and at the LRV between the
      aorta and the superior mesenteric artery. RESULTS: The mean AP diameters of the
      LRV were 10.0 mm +/- 2.0 (standard deviation) and 1.9 mm +/- 1.0 (ratio, 5.0 +/-
      2.3) in the patient group and 7.2 mm +/- 1.8 and 2.3 mm +/- 0.6 (ratio, 3.3 +/-
      1.1) in the control group. The PVs at the two locations were 14.2 cm/sec +/- 2.5
      and 110.7 cm/sec +/- 35.8 (ratio, 7.9 +/- 2.7) in the patient group and 18.6
      cm/sec +/- 3.7 and 50.9 cm/sec +/- 27.9 (ratio, 2.8 +/- 1.5) in the control
      group. Differences in AP diameter and PV were statistically significant between
      the two groups (P < .01). CONCLUSION: Doppler US of the LRV with measurement of
      the AP diameter and PV may be useful in diagnosing the nutcracker syndrome.

PMID- 8539414
TI  - Testicular adrenal rest tissue in congenital adrenal hyperplasia: findings at
      Gray-scale and color Doppler US.
AB  - PURPOSE: To study the ultrasound (US) features of scrotal adrenal rest tissue in
      congenital adrenal hyperplasia (CAH). MATERIALS AND METHODS: Gray-scale and color
      Doppler US examinations were performed of scrotal masses in eight patients. The
      masses were evaluated for size, location, echogenicity, sound attenuation, and
      vascularity. RESULTS: Seventeen intratesticular masses and one extratesticular
      mass were examined. All were hypoechoic except for one intratesticular mass that
      contained hyperechoic areas. Six masses demonstrated sound attenuation. The
      mediastinum testis was found in the center of 11 of the 17 intratesticular
      masses. At color Doppler US, six masses were hypervascular, seven were
      isovascular, and five were hypovascular relative to the normal testicle. All
      intratesticular masses contained vascular structures that entered them from the
      normal testis without change in course or caliber. Eleven masses showed a spoke
      like pattern of converging vessels. CONCLUSION: The US features of scrotal
      adrenal rests assist diagnosis of CAH.

PMID- 8539415
TI  - D-1 receptors in neurology and psychiatry an overview.

PMID- 8539416
TI  - D-1 receptor mediated modulation of the release of gamma-aminobutyric acid by
      endogenous dopamine in the basal ganglia of the rat.
AB  - 1. Presynaptic D1 receptors are present on GABAergic terminals of neostriatal
      projections. 2. By activating these receptors, exogenous dopamine enhances the
      release of GABA. 3. Here the authors have explored whether endogenous dopamine
      was also able to activate the receptors, thus enhancing GABA release. 4. The
      effect of methamphetamine, a dopamine releaser, on the release of tritiated GABA
      was studied in slices of substantia nigra pars reticulata, entopeduncular nucleus
      and caudate-putamen, targets of the striatal projections. 5. Methamphetamine
      enhanced the release of the label. However the enhancement required an intact
      dopaminergic innervation, since it was lost in slices isolated from rats with 6
      hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system. 6. The
      activation of the receptors by endogenous dopamine was also judged by the effect
      of the selective D1 antagonist SCH 23390 in potassium depolarized slices. By
      preventing activation of the receptors by dopamine released as result of
      depolarization, the antagonist reduced GABA release. In 6-OHDA lesioned slices,
      no reduction was observed, even though the slices were also depolarized. 7. The
      results indicate that endogenous dopamine enhances GABA release from striatal
      terminals in the pars reticulata of the substantia nigra, entopeduncular nucleus
      and caudate-putamen. This would facilitate GABAergic neurotransmission. 8. The
      study suggests that the function of DA in the basal ganglia is widespread,
      modulating not only the firing of the striatal efferent neurons but also the
      transmission of the fired impulses across synapses in the target nuclei of these
      neurons.

PMID- 8539417
TI  - Desensitization of the D1 dopamine receptors in rats reproduces a model of escape
      deficit reverted by imipramine, fluoxetine and clomipramine.
AB  - 1. The present study investigated the effect of long-term D1 dopamine receptor
      stimulation on an animal model of depression derived from the learned
      helplessness paradigm. 2. The model used is based on the escape deficit produced
      by a series of unavoidable shocks administered to rats 24 h before the test
      session. SKF 38393 administered acutely, completely prevented the development of
      animal hyporeactivity, while given repeatedly produced tolerance to its own
      protective effect. Moreover it also reduced the spontaneous escape reactivity of
      rats not exposed to the inescapable shocks. Animals chronically receiving SKF
      38393 and showing a clearcut escape deficit, were treated daily with either
      imipramine, fluoxetine, or clomipramine. After 21 days of combined treatment the
      3 antidepressants appeared equally effective in reverting the behavioral deficit.
      Moreover, long term administration of both imipramine or SKF 38393 down regulated
      D1 dopamine receptor number in the prefrontal cortex, while the association of
      the two drugs resulted in a receptor density similar to that of control rats. 3.
      The present results further support the crucial role played by D1 dopamine
      receptors in the control of animal reactivity to stressful stimuli and in the
      mechanism of action of imipramine. Moreover they show that the D1 dopamine
      receptor related escape deficit is sensitive also to compounds selectively acting
      through the serotonergic neuronal system.

PMID- 8539418
TI  - The D-1 dopamine receptor: past, present and future an idiosyncratic review.
AB  - 1. Key events in the experimental investigation of the D-1 dopamine receptor are
      reviewed. 2. The efficacy of D-1 receptor agonists in the treatment of
      experimental parkinsonism in MPTP-treated primates is demonstrated. The
      diminished dyskinetic liability of D-1 agonists is discussed. 3. The significance
      of the dopa-induced dyskinesias is discussed from the perspective of
      deterministic chaos. The unpredictibility and irreproducibility of dyskinetic
      movements is highlighted and compared with features of the logistic equation. 4.
      The authors propose that the dopa-induced dyskinesias should be considered to be
      a manifestation of a chaotic process within the basal ganglia. The loss of the
      dopaminergic innervation and the subsequent repeated exposure to dopamine
      (derived from the exogenous dopa administered to the subjects) alters the
      response properties of the basal ganglia circuitry so that stimulation of
      dopamine receptors now elicits the dyskinetic movements.

PMID- 8539419
TI  - Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and
      new perspectives.
AB  - 1. The dopamine (DA) D1-receptor family is highly represented in the mammalian
      brain and particularly in the nigrostriatal system, whose integrity is crucial
      for the execution of motor performances. 2. In the last decade, our understanding
      of the electrophysiology of D1 receptors on caudate-putamen neurons has greatly
      improved. The effects of the activation of striatal D1 receptors were studied by
      extracellular single unit recordings in the intact animal as well as by
      intracellular recordings in rat brain slice preparation. More recently, whole
      cell recordings on isolated striatal neurons have further addressed this issue
      and confirmed the inhibitory modulatory role of D1 receptor on the electrical
      activity of striatal neurons. 3. Several important questions, however, concerning
      the functional effects of D1 receptor activation in the basal ganglia are still
      debated: the cellular segregation of the distribution of D1-D2-like receptors,
      their synergistic or opposite functional roles at the second messenger level, the
      effects of D1 receptor activation on the transmitter release and the
      modifications of D1 receptor pharmacology in dopamine-denervated striata. 4. A
      different perspective will also be discussed: the involvement of D1 receptors in
      long-term changes of synaptic efficacy in the striatum as a possible correlate of
      motor learning.

PMID- 8539420
TI  - D1/D2 actions of dopaminergic drugs studied with [14C]-2-deoxyglucose
      autoradiography.
AB  - 1. To define the neural circuits activated by dopaminergic stimulation in rat
      models of parkinsonism, the author studied the effects of L-dopa and selective D1
      and D2 agonists on RCGU in rats with unilateral 6-OHDA substantia nigra lesions.
      2. Systemic administration of L-dopa markedly increased RCGU in the EP and SNr
      ipsilateral to the nigral lesions; it is suggested that this represents metabolic
      activity primarily in axon terminals of GABAergic striatal projection neurons.
      These effects were reproduced by selective D1, but not D2, dopamine agonists, and
      were blocked completely by a D1 antagonist, indicating their critical dependence
      on D1 stimulation. L-dopa moderately increased RCGU in the STN; this effect was
      reproduced by D1 and D2 agonists and was blocked completely only by combined D1
      and D2 antagonist pretreatment. 3. The RCGU data support a direct stimulatory
      action of dopamine, formed from L-dopa, on D1 receptor-bearing striatal GABAergic
      neurons projecting to the EP and SNr as well as a net stimulatory action on the
      GP output to the STN. 4. The marked D1-mediated RCGU increase in the SNr
      ipsilateral to the dopamine depletion contrasts with the modest increase seen on
      the contralateral side and in naive rats, suggesting that the enhanced RCGU
      response to D1 stimulation is an index of dopaminergic supersensitivity. The
      stimulatory effect of the D1 agonist SKF 38393 on RCGU in the SNr is enhanced 6
      12 hours after acute dopamine depletion with reserpine/AMPT indicating that
      supersensitive responses develop within this rapid time frame. 5. The RCGU data
      indicate that D1 receptor stimulation contributes importantly, in an anatomically
      selective manner, to the effects of L-dopa on basal ganglia circuits and that the
      response to D1 stimulation is rapidly modifiable by dopamine depletion.

PMID- 8539421
TI  - Behavioural pharmacology of 'D-1-like' dopamine receptors: further subtyping, new
      pharmacological probes and interactions with 'D-2-like' receptors.
AB  - 1. D-1 receptors are now recognised to play a critical psychopharmacological role
      in the regulation of unconditioned motor and numerous other aspects of behaviour.
      2. There appears to exist a broad family of 'D-1-like' receptors in terms both of
      differential coupling to distinct messenger/transduction mechanisms and of gene
      cloning, whose behavioural roles remain to be clarified. 3. The adenylyl cyclase
      inhibiting benzazepine SK&F 83959 induces behavioural responses in rats that are
      similar to those induced by the full efficacy cyclase-stimulating isochroman A
      68930 but not to those induced by its high efficacy partial agonist benzazepine
      congener R-6-Br-APB; these data indicate roles for individual 'D-1-like'
      receptors in mediating distinct elements of dopaminergic behaviour. 4. The
      putative D-1 autoreceptor agonist B-HT 920 and the putative D-3 agonist 7-OH-DPAT
      demonstrate different behavioural profiles when given both alone and in
      combination with the selective 'D-1-like' antagonist BW 737C; D-3 receptors may
      participate in cooperative/synergistic but not in oppositional 'D-1-like': 'D-2
      like' interactions. 5. Such interactions apparent at the level of behaviour are
      complemented by evidence for similar interactions at numerous alternative levels
      of function, though these may differ between rodent and primate species. 6. A
      broader range of more selective agonists and antagonists, able to distinguish
      between individual members of the 'D-1-like' and of the 'D-2-like' receptor
      families are needed to clarify these issues.

PMID- 8539422
TI  - Psychosis in Parkinson's disease: diagnosis and treatment.
AB  - 1. This article reviews the prevalence, diagnosis, pathophysiology and management
      of psychosis in Parkinson's disease. 2. Psychosis in Parkinson's disease has been
      associated with all antiparkinsonian medications. The most common symptoms are
      vivid disturbing dreams, visual hallucinations and paranoid delusions. 3. The
      emergence of psychosis reduces the patient's functional capacity and increases
      caregiver burden. It also poses a therapeutic dilemma because effective treatment
      of psychotic symptoms may result in worsening of motor symptoms and vice versa.
      4. Increased physician awareness is essential for proper diagnosis and
      management. Withdrawal of anticholinergic medications and amantadine followed by
      levodopa dose adjustment is effective in many patients. 5. Atypical neuroleptics,
      in low doses, may be successful when other measures have failed. However, these
      agents are not approved for treating Parkinsonian psychosis and must be
      considered as investigational therapies.

PMID- 8539423
TI  - Depressive symptoms in the elderly: association with total white blood cell
      count.
AB  - 1. The white blood cell (WBC) count in those with high depressive symptoms and
      non-depressed participants in the Established Populations for Epidemiologic
      Studies of the Elderly (EPESE) were compared. 2. Of 3769 participants 10.8% had
      high depressive symptoms as assessed by the Centers for Epidemiologic Studies
      Depression (CES-D) Scale. The mean white blood cell count was higher in the high
      depressive symptoms group compared to the non-depressed group (6.8 +/- 0.12 x
      10(9) WBC/1 and 6.5 +/- 0.03 x 10(9) WBC/1, respectively, p < 0.01). 3. Because
      older adults frequently have disabling chronic conditions which could both
      influence their leukocyte count and cause depressive symptoms, models were
      developed which controlled for the potential confounding. Even after adjusting
      for potential confounders, high depressive symptoms were still associated with
      higher white blood cell counts.

PMID- 8539424
TI  - Quantified EEG changes associated with a positive clinical response to clozapine
      in schizophrenia.
AB  - 1. The authors conducted a retrospective exploratory computerized EEG study on
      the effect of clozapine in treatment-refractory schizophrenics, 10 high
      responders (HRs) and 10 low-responders (LRs), in an attempt to correlate
      amplitude but especially coherence changes with a positive clinical response to
      clozapine. 2. EEGs with eyes closed were obtained before and during a clozapine
      treatment. Both groups had a similar drug profile with regards to non-clozapine
      medication. Probability maps were computed to illustrate changes of amplitude and
      coherence (for all combinations of paired electrodes) for 4 frequency bands
      (theta, alpha, beta 1 and 2). 3. The effect on AMPLITUDE was a generalized
      increase in lower bands and a decrease in anterior regions in higher bands of
      both HRs and LRs. Considerable changes of COHERENCE were observed on a wide set
      of paired electrodes in most frequency bands with some electrodes involved in HRs
      but uninvolved or differently involved in LRs suggesting differences in selected
      brain regions. 4. Changes of coherence but not amplitude were correlated with
      changes on the BPRS, thus to clinical improvement, and concerned mostly the right
      anterior-medial temporal (T4) and central (C4) electrodes paired with prefrontal
      electrodes, left central (C3), temporal (T3) and parietal (P3) electrodes in the
      theta band. 5. Clozapine has both generalized and regional effects as can be
      suspected considering its effect on many subtypes of brain receptors. A brain
      dysfunction centralized on the right anterior-medial temporal region may
      characterize treatment-refractory schizophrenics.

PMID- 8539425
TI  - Association of biogenic amine metabolites with symptomatology in delusional
      (psychotic) and nondelusional depressed patients.
AB  - 1. The levels of the main norepinephrine, serotonin, and dopamine metabolite
      excretion in the urine, MHPG, 5HIAA and HVA respectively, were measured in 84
      patients with major depressive disorder, 34 delusional (psychotic) and 50
      nondelusional (DSM-III-R criteria). 2. Associations with the 17 items of the HDRS
      were evaluated using the multiple regression analysis model. In the delusional
      group, MHPG excretion was positively related to the scores in the items of
      depressed mood (p = 0.04), middle insomnia (p = 0.008) and genital symptoms (p =
      0.001). 5HIAA excretion was negatively associated with late insomnia (p = 0.02),
      work and interests (p = 0.001) and genital symptoms (p = 0.007). HVA was
      positively related to agitation (p = 0.043). In the nondelusional group the only
      association found was between agitation and HVA excretion (p = 0.03).

PMID- 8539426
TI  - Cerebral and cerebellar diaschisis following carbamazepine therapy.
AB  - 1. The regional cerebral blood flow was studied by SPECT in patients with partial
      epilepsy before and after 30 days of monotherapy with carbamazepine (CBZ). 2.
      Both a qualitative visual interpretation and a semiquantitative analysis of SPECT
      was performed. All patients underwent EEG, CT scan, and MRI studies. The CBZ
      serum concentrations were assayed. 3. After therapy, in three patients with focal
      epilepsy, both a crossed cerebral and cerebellar diaschisis were observed, with
      respect to the side of the epileptic focus in the opposite hemisphere. No
      morphologic changes were detected at MRI in the cerebral or cerebellar remote
      hypometabolic areas found at SPECT. 4. CBZ may have a depressant action on the
      corticopontocerebellar pathways and on the corticocallosal connections.

PMID- 8539427
TI  - Decrease in red blood cell L-tryptophan uptake in schizophrenic patients:
      possible link with loss of impulse control.
AB  - 1. Kinetic parameters of erythrocyte L-tryptophan (TRP) uptake (Vmax, maximal
      velocity and Km, Michaelis constant) were determined in 19 neuroleptic-free
      schizophrenic patients and in 19 healthy volunteers. Both Vmax and Km values were
      significantly lower in schizophrenic patients than in controls. 2. Mean Vmax
      value was found to be lower in patients who had attempted suicide than in
      patients who had not. No difference was observed when patients were subdivided on
      the basis of the violence of suicide attempts. 3. A significant negative
      correlation was observed between Vmax and scores on the loss of impulse control
      item as assessed on the PANS scale. 4. Decrease in red blood cell L-TRP uptake
      reflects a disturbance in the peripheral metabolism of TRP that may result in a
      deficiency of the plasma L-TRP availability on which the central serotonin (5HT)
      synthesis closely depends. 5. In addition, the results suggest that the
      alteration in RBC L-TRP uptake is associated with loss of impulse control in
      schizophrenic patients.

PMID- 8539428
TI  - Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by
      electrical stimulation of hippocampus and amygdala in the rabbit.
AB  - 1. The differential role played by blockade of D-1 or D-2 dopamine receptors in
      mechanisms underlying seizures was studied in a model of EEG after-discharge
      induced by electrical stimulation of selective brain regions (dorsal hippocampus
      and amygdala) in the rabbit. 2. The D-2 antagonist haloperidol (1 mg/Kg)
      increased significantly after-discharge duration after stimulation of either
      hippocampus or amygdala and lowered after-discharge threshold in few animals. 3.
      The D-1 antagonist SCH 23390 (0.3 mg/Kg) caused no changes following stimulation
      of amygdala and reduced after-discharge duration when hippocampus was stimulated.
      4. Haloperidol exerted a proconvulsant action in this experimental model, having
      a clearer influence on D-2 receptors. SCH 23390 had no effect on amygdala whereas
      it exerted protection on the hippocampus. 5. The present data suggest that D-1
      and D-2 receptors have different roles in generating and spreading the epileptic
      activity.

PMID- 8539429
TI  - Effect of isolation on behavioural models involving serotonergic 5-HT2 and 5-HT1A
      receptors.
AB  - 1. The effect of 7 days of isolation were observed in mice on behavioural models
      involving 5-HT2 and 5-HT1A receptors. 2. The sensitivity of 5-HT2 receptors as
      assessed through L-5-HTP or 5-MeODMT induced head-twitches was reduced. 3. The
      sensitivity of the 5-HT1A receptors implicated in the 8-OH-DPAT induced feeding
      was unchanged. 4. The sensitivity of the 5-HT1A receptors involved in the 8-OH
      DPAT induced hypothermia was diminished. 5. On the whole, these results show that
      after 7 days of isolation, the responses to the stimulation of serotonergic
      receptors is unchanged or diminished according to both the receptor's subtype and
      the model used.

PMID- 8539430
TI  - Lidocaine reduces the hypoxia-induced release of an excitatory amino acid analog
      from rat striatal slices in superfusion.
AB  - 1. Lidocaine has been extensively investigated as a potential neuroprotective
      drug against ischemia-induced neurodegeneration without reaching any satisfactory
      conclusion. 2. The present work evaluates the effect of lidocaine -17 microM- on
      the hypoxia-induced release of tritiated D-aspartate from rat striatal slices in
      superfusion. 3. Hypoxia resulted in a significant increase in the amount of D
      aspartate released from striatal slices preloaded with the tritiated excitatory
      amino acid analog. 4. The addition of lidocaine to the superfusion solution
      resulted in a drastic reduction in the amount of D-aspartate release evoked by
      hypoxia, rendering it close to normal values.

PMID- 8539431
TI  - An animal model for mania: preliminary results.
AB  - 1. In human bipolar patients mania and bipolar depression are both characterized
      by decreased membrane Na,K-AtPase activity. Additionally, digoxin neurotoxicity
      in patients frequently presents with symptoms of mania or depression. 2. These
      findings suggest that central nervous system Na,K-ATPase inhibition may play a
      pathophysiologic role in bipolar illness. 3. The authors tested this hypothesis
      by administering intracerebroventricular (i.c.v.) ouabain to rats at sublethal
      doses. The authors then measured behavioral activity as total square crossings in
      an open field. 4. Motoric activity was significantly increased by i.c.v.
      administration of 5 microliters of ouabain at 10(-3) M. This preliminary study
      suggests that i.c.v. ouabain administration may provide a useful animal model of
      mania that is based on observed biochemical changes in humans.

PMID- 8539432
TI  - TJS-010, a new prescription of oriental medicine, antagonizes tetrabenazine
      induced suppression of spontaneous locomotor activity in rats.
AB  - 1. The authors have determined the effect of TJS-010, a new prescription of
      oriental medicine, on the locomotor activity in rats. 2. Tetrabenazine(TBZ)
      decreased the spontaneous locomotion in rats, and attenuated the contents of
      amines and increased their metabolism in various regions in rat brain. 3. TJS-010
      inhibited the locomotor suppression induced by TBZ: however, neither amine
      contents nor their metabolism was not altered, which suggested that TJS-010
      postsynaptically modulated the transmission or transduction. 4. Imipramine also
      inhibited the decrease in locomotion induced by TBZ. 5. These results suggest a
      possibility that TJS-010 has an antidepressive effect.

PMID- 8539433
TI  - Study of the mechanisms involved in behavioral changes induced by flunitrazepam
      in morphine withdrawal.
AB  - 1. The attenuation of morphine withdrawal syndrome by acute benzodiazepine
      administration has been well documented. However, the pharmacological mechanisms
      implicated in this effect remain unclear. 2. In this study, the possible
      participation of noradrenergic, serotonergic and benzodiazepine receptors on
      flunitrazepam-modified morphine withdrawal syndrome was investigated in mice.
      Flunitrazepam was associated to the noradrenergic antagonists prazosin (1 mg/kg)
      and propranolol (0.5 mg/kg), the serotonergic agents ritanserine (1 mg/kg) and p
      chloro phenylalanine (600 mg/kg), the benzodiazepine antagonist flumazenil (10
      mg/kg), and the benzodiazepine partial inverse agonist Ro 15-4513 (5 mg/kg). 3.
      The decrease in jumping behavior-induced by flunitrazepam was potentiated by
      prazosin, while ritanserine, flumazenil and Ro 15-4513 blocked this effect. 4.
      Flunitrazepam-induced increase on wet dog shake frequency was partially reduced
      by flumazenil, and strongly antagonized by ritanserine and Ro 15-4513. 5.
      Noradrenergic and serotonergic systems seem to be primarily implicated in the
      changes induced on jumping and wet dog shakes respectively. These modifications
      are induced through the activation of the benzodiazepine receptors.

PMID- 8539434
TI  - In memoriam--Michaela Modan (1935-1993).

PMID- 8539435
TI  - Cancer prevention policy. Authority and responsibility--who is in charge of
      carcinogenic hazards and their sequelae?

PMID- 8539436
TI  - Setting and monitoring health objectives for the nation.
AB  - Healthy People 2000 is a national effort to focus and coordinate a wide variety
      of efforts to improve the health and longevity of the American people. By
      establishing specific objectives, each with measurable targets for the year 2000,
      the success of programs to improve health and prevent disease can be assessed.
      The cancer objectives concentrate on the leading sites that account for more than
      half of all cancer deaths. They include risk reduction objectives to modify
      individuals' behaviors towards more healthful practices, and services and
      protection objectives to enhance counselling and early detection efforts.
      National surveys conducted by the National Center for Health Statistics are in
      place to monitor the progress towards accomplishment of these objectives and to
      guide policies for effective actions.

PMID- 8539437
TI  - The health of the Polish population.

PMID- 8539438
TI  - The etiology of breast cancer--from epidemiology to prevention.
AB  - Breast cancer is likely caused by the interaction of exposure to environmental
      carcinogens at an early age, resulting in initiation of neoplastic transformation
      and growth factors that determine the likelihood of progression to clinical
      disease. The environmental carcinogens are numerous (each contributing relatively
      little to overall risk) and probably interact with genetic "host susceptibility".
      Most women probably have subclinical breast cancer. The growth of the breast
      cancer is related to sex-hormone levels at the breast and stimulation of local
      growth factors. Genetic factors (i.e. host susceptibility including polymorphisms
      related to the enzymes that affect hormone levels, estrogen/progesterone
      receptors, and protein synthesis) are probably very important. Reproductive and
      menstrual patterning during the premenopause, especially related to pregnancy,
      menstrual cycling and lactation are very important determinants of the risks of
      breast cancer. More attention needs to be placed on the determinants of menstrual
      cycling and hormone levels in premenopausal women, especially the relationship of
      obesity, fat distribution and exercise. The degree of obesity, age at onset of
      obesity, weight gain (peri- to postmenopausal), and possibly body fat
      distribution are the major determinants of postmenopausal estrogen levels are key
      risk factors for postmenopausal breast cancer. Dietary fat, fiber, and perhaps
      other nutrients, also contribute to blood estrogen levels. Other hormones,
      especially insulin and insulin-like growth factors, and possibly testosterone and
      androgens, may also contribute to the increased risk of breast cancer. The
      reduction of breast cancer incidence and mortality will depend, primarily, on
      modifications of women's lifestyles which would move them from higher to lower
      estrogen characteristics.

PMID- 8539439
TI  - Classification of hematopoietic regions in out-of-phase T1-weighted images: a
      quantitative comparison study with T1-weighted and STIR images.
AB  - The hematopoietic regions were classified into two groups on the basis of out-of
      phase T1-weighted images (op-T1WI): regions with lower intensity than that of
      muscle (LH) and regions with intensity equal to or higher than that of muscle
      (HH). We quantitatively evaluated the differences in signal intensity between LH
      and HH in order to examine this classification. Forty-two hematopoietic areas in
      aplastic anemia were classified into two groups of 23 LH and 19 HH. The signal
      ratios of hematopoietic areas to muscle on T1WI and STIR were calculated, and the
      differences between LH and HH were statistically evaluated. The signal ratios of
      LH were significantly higher on T1WI and lower on STIR than those of HH (unpaired
      t-test, p < 0.05). This result indicated that LH consisted of more hypocellular
      marrow than HH. Op-T1WI were useful in differentiating between LH and HH and
      defining the degree of hematopoiesis in aplastic anemia.

PMID- 8539440
TI  - Postcontrast 3D-TOF-MR angiography of intracranial venous angiomas.
AB  - The clinical value of three-dimensional time-of-flight magnetic resonance
      angiography (3D-TOF-MRA) was assessed in 15 patients with intracranial venous
      angiomas (VAs), by comparing results thereof with those of postcontrast T1
      weighted MR images (MRIs). All 15 VAs were identified both on the postcontrast
      MRIs and MRAs. The MRAs surpassed the MRIs in imaging entire structures,
      including the draining veins of the supratentorial VAs. For the infratentorial
      VAs, the MRAs and the MRIs were of equal value. Although the addition of MRA to
      the MRI procedure incurs more time and expense, the complete structure of the VA
      can thereby be identified three-dimensionally on MRA. Conventional angiography is
      apparently not required for the confirmation of a VA. Thus, it is concluded that
      MRA is very useful for diagnosing VAs.

PMID- 8539441
TI  - C-reactive protein as an indicator of effect and of adverse reaction to
      transcatheter arterial embolization.
AB  - Serum C-reactive protein (sCRP) levels were measured before and after angiography
      and transcatheter arterial embolization (TAE) in 25 patients (four angiography,
      21 TAE for hepatocellular carcinoma) to examine the correlation of sCRP to
      patients' reaction to TAE and the efficacy of TAE. Four patients without TAE
      showed little elevation of sCRP. Twenty-one patients with TAE showed a
      significant increase in sCRP. Peak levels of sCRP in the patients who achieved
      partial response were higher than those of the no-change group after TAE (p =
      0.005). Peak sCRP levels of patients who showed an adverse reaction to TAE were
      higher than those of patients with no adverse reaction (p = 0.02). Increased sCRP
      after TAE reflects not only the degree of untoward reaction but also the
      effectiveness of TAE. Therefore, measurement of sCRP may be a useful means to
      assess the effect of TAE.

PMID- 8539442
TI  - Dynamic MRI with slow injection of contrast material for the diagnosis of
      pituitary adenoma.
AB  - Magnetic resonance (MR) imaging of pituitary adenoma is usually carried out in
      dynamic studies with bolus contrast material injections, with the result that few
      strong images are obtained. Dynamic studies using a slowly injected contrast
      material were carried out in 14 cases of pituitary adenomas. The examinations
      were performed with a 1.5 Tesla superconducting MR imaging system using the spin
      echo technique. Gd-DTPA (0.1 mmol/kg) was slowly injected (within 90 sec) by
      hand, providing seven to nine dynamic images during 350 sec from the start of
      injection. The average time to reach the maximum signal intensity was 170.6 sec
      in adenoma and 156.2 sec in normal gland tissue. The maximum contrast signal
      intensity ratio of adenoma to normal gland was 0.527 in the fifth image. The
      contrast of adenoma to normal gland tissue was calculated by the following
      formula: ASII (adenoma signal intensity index) = (adenoma signal intensity-tissue
      signal intensity)/tissue signal intensity. The most remarkable contrast between
      adenoma and normal tissue was obtained from the fourth to eighth images. In other
      words, we could obtain the strongest contrast at 144.8 sec to 299.6 sec from the
      start of contrast injection. Our results with slow injection suggest that
      stronger images can be obtained a longer period after contrast injection.

PMID- 8539443
TI  - Tuberculosis of the prostate: MR imaging.
AB  - Tuberculosis of the genitourinary tract is still encountered in routine
      examinations. We present a case of tuberculosis of the prostate with its MR
      findings.

PMID- 8539445
TI  - MR imaging in alveolar echinococcosis of bone.
AB  - We report two cases of alveolar echinococcosis (AE) of the bone, and present the
      computed tomography (CT) and magnetic resonance (MR) imaging findings of these
      surgically proven cases of AE of the ilium and clavicle. CT and MR imaging showed
      destruction of the ilium and clavicle, and numerous cysts of the bone and
      surrounding tissues. Moreover, CT and MR imaging clearly demonstrated spread of
      the parailiac region and superior mediastinum. CT and MR imaging were very useful
      in determining the extent of surgery. Our experience suggested that CT and MR
      imaging are complementary studies.

PMID- 8539444
TI  - Anterior mediastinal schwannoma: a case report.
AB  - The most common neoplasms of the mediastinum are those of neurogenic origin, and
      the majority of these arise in the posterior compartment. We report a case of
      benign schwannoma originating in rare location, the anterior mediastinum, and its
      imaging findings.

PMID- 8539446
TI  - Primary hepatic neuroendocrine carcinoma with multiple metastases: a case report.
AB  - We report a rare case of primary hepatic neuroendocrine cell carcinoma with
      multiple metastases to the liver, lung, diaphragm, bone, and pancreas. The
      patient was a 45-year-old man with jaundice and a large hepatic tumor measuring
      12 x 16 cm at autopsy. Located in the right lobe, it was hyperechoic and
      inhomogeneous on US, a diffusely low density mass that contained capsule- and
      septum-like structures enhanced by contrast medium on CT, an inhomogeneously low
      intensity mass with much lower intensity foci on T1-weighted MRI, and a diffusely
      high intensity mass containing small higher and lower intensity foci on T2
      weighted MRI. These findings are similar to those of a few previously reported
      cases, but are not specific to this tumor.

PMID- 8539447
TI  - Case report: breast hamartoma: MR findings.
AB  - We report a case of breast hamartoma which was diagnosed by magnetic resonance
      (MR) imaging and describe the MR features of this lesion. There was a perfect
      correlation between the findings at MR imaging and the macroscopic appearance of
      the tumor.

PMID- 8539448
TI  - Chemodectoma of the carotid body treated with radiation therapy: a case report.
AB  - The response to radiation of a huge chemodectoma arising in the carotid body is
      reported. Diagnostic imaging and a resected specimen demonstrated a rich supply
      of blood vessels in the tumor. A radiation dose of 40 Gy was applied to the tumor
      over four weeks with a 10 megavolt photon beam. The tumor had a non-enhanced area
      in the middle 1.5 years after radiation therapy. The whole tumor as well as the
      non-enhanced area was obviously shrunken three years after treatment.

PMID- 8539449
TI  - Observation of glucose metabolism in the rat liver by in vivo 13C MR spectroscopy
      without proton decoupling.
AB  - Glucose metabolism in rat liver was investigated by in vivo 13C-MR spectroscopy
      using [1-13C]glucose. Experiments were performed with a 7.05 Tesla small bore MR
      system using a 13C surface coil without 1H decoupling. Sprague-Dawley rat was
      anesthetized and kept in the spine position. [1-13C]glucose (99% enriched) was
      injected intravenously in a dose of 1 g per kg of body weight. The circular
      surface coil of 25.4 mm in diameter was placed on the surgically exposed liver in
      the incised abdomen. A total time of one scan was about 8 min and time course for
      glycogenesis was observed every 10 min, for total 90 min. The in vivo 13C-1
      carbon resonances of hepatic glucose and glycogen were well resolved in spite of
      splitting by J-coupling, enabling the time course for the relative change in
      concentrations for both metabolites to be established simultaneously. The 13C
      resonance of glucose gradually decreased, and the 13C resonance of glycogen
      gradually increased to peak level at 40 min after the injection of [1
      13C]glucose. We have developed a simple method of 13C-MR spectroscopy for use in
      rat liver.

PMID- 8539450
TI  - Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in
      cervical carcinoma.
AB  - Apoptosis is an important mechanism of cell death in tumours and it is seen both
      prior to and following radiotherapy. In this study patients with proven carcinoma
      of the cervix had measurement made of the percentage of apoptotic cells
      (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic
      radiosensitivity (SF2), already shown to be a predictor of outcome, had
      previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki
      67 antigen staining were also recorded as markers for proliferation. Patients
      were divided into those with an AI above or below the median and in general
      increasing apoptosis was associated with poor prognosis. The 5-year survival rate
      for tumours with an AI below the median was 79% and was significantly greater
      than the rate of 47% for those with an AI above the median (p = 0.003). There was
      also a significantly increased 5-year local recurrence-free rate for patients
      with an AI below the median compared with those with an AI above the median (79
      versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic
      indicators. Patients with both an SF2 and AI value above the median did badly
      (25% 5-year survival, 46% local control) compared with those with an SF2 and AI
      below the median (80% 5-year survival, 100% local control). Apoptosis showed
      correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67
      antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to
      patient outcome. This suggests that while apoptosis may be a reflection of tumour
      proliferation this cannot in itself explain the ability of apoptosis to predict
      clinical outcome for this series of patients. The study raises the possibility of
      AI and SF2 being used together as predictors of tumour response to radiotherapy.

PMID- 8539451
TI  - Multivariate analysis of prognostic factors in 75 patients with soft tissue
      sarcoma.
AB  - The results of 75 patients with soft-tissue sarcomas treated by the combination
      of local surgical excision plus postoperative radiotherapy are reported. Thirty
      five tumors were situated in the extremities, 32 in the trunk, and eight in the
      head and neck. Twenty-eight tumors were high grade, 33 intermediate and 14 low
      grade. Sixty-two patients had complete resections (wide or marginal) and 13
      incomplete resections (intralesional). Radiation was administered with a
      shrinking-field technique (median total dose, 64 Gy; range, 50-78). Twenty-five
      patients developed local recurrence (33%). The 5-year local control rate was 67%.
      On univariate analysis, a tumor site other than extremity (p < 0.05), unfavorable
      histology (p < 0.01), and incomplete resection (p < 0.01) were poor risk factors
      for local recurrence. When multivariate analysis were performed, only incomplete
      resection (relative risk (RR) 7.2) remained a poor risk factor. The 5-year
      overall survival rate was 50.5% for the entire group. Following a univariate
      analysis of host tumor and treatment-related factors, a tumor site other than
      extremity (p < 0.05), high tumor grade (p < 0.01) unfavorable histology (p <
      0.05), and incomplete tumor resection (p < 0.01) were found to significantly
      increase the risk of further tumor death. Multivariate analysis found high tumor
      grade (RR 5.6), and incomplete resection (RR 7) to be independent poor risk
      factors for survival.

PMID- 8539452
TI  - Where exactly does failure occur after radiation in head and neck cancer?
AB  - Loco-regional recurrence in squamous cell carcinoma of the head and neck can
      occur at the site of the original primary tumour or in the marginal zone at its
      periphery. While nodal recurrence may occur in previously involved nodes or in
      uninvolved nodes within or outside the treatment volume. The exact site of
      failure was determined in 89 patients treated with radical radiotherapy for
      carcinoma of the head and neck. Of 73 patients who failed at the primary site 71
      (97%) did so within the site of the original tumour; only two patients developed
      a marginal recurrence. Of the 30 (93%) patients with N1-3 disease who later
      showed failure in the lymph nodes, 28 (93%) did so at their original site of
      disease. These results support the view that when radiation fails it usually does
      so in the centre of the tumour. In order to improve our results we need to deal
      with radioresistance at the site of mass disease. Ways of approaching this
      include the combination of surgery with radiotherapy, the addition of a
      sensitiser or an increase in the dose to the tumour mass by boosting a 'mini'
      volume using conformal techniques.

PMID- 8539453
TI  - Radiation induced G1-block and p53 status in six human cell lines.
AB  - Considerable attention has recently been focused on the fact that the tumor
      suppressor protein p53 is involved in the cellular response to radiation. In its
      wild-type form the protein appears to control a cell cycle checkpoint, preventing
      entry into S-phase following DNA damage. A number of authors observed a radiation
      induced G1-block in cells expressing wild-type p53, but not in p53 mutant cells.
      We obtained similar results with four human tumour cell lines as well as two
      strains of human fibroblasts, whose p53 status was ascertained at the protein as
      well as DNA levels. In addition to cell cycle delays in exponentially growing
      cell cultures, we have studied the possible role of the p53 in the transition
      from quiescence to active proliferation. Cells were irradiated after 6 days of
      serum-starvation and labelled with BrdU at different times after addition of
      fresh medium. Entry into S-phase was found to be delayed by several hours in the
      p53 wild-type cells, but no such effect was observed in the p53 mutants. Where a
      delay occurred, it was roughly proportional to the X-ray dose. Although it
      remains to be clarified, whether the cells were delayed only in G1 or also in G0,
      it is interesting to note that entry into S-phase can be delayed by irradiation
      in a quiescent state immediately before serum-stimulation, provided the cells are
      wild-type with respect to p53. Certain differences in the cell cycle response of
      transformed and untransformed cells were noted.

PMID- 8539454
TI  - Comparison of treatment techniques for conformal radiotherapy of the prostate
      using dose-volume histograms and normal tissue complication probabilities.
AB  - The aim of this study was to evaluate the relative merits of the coplanar field
      arrangements most frequently used for conformal radiotherapy of the prostate
      using dose-volume histograms and normal tissue complication probabilities
      (NTCPs). Twelve patients with early prostate cancer underwent a planning CT scan
      of the pelvis. Isocentric plans for each patient were devised using three, four,
      six and eight conformal fields and beam-weights optimised using fast simulated
      annealing to give a dose homogeneity across the planning target volume of +/- 5%
      or better while minimising irradiation of the relevant organs at risk. The plans
      were then evaluated using dose-volume histograms of the organs at risk (bladder,
      rectum and both femoral heads) and the Lyman model of normal tissue complication
      probability for the rectum. Analysis of dose-volume histogram data averaged over
      the 12 patients indicates an advantage for six (p = 0.002) and eight (p = 0.0001)
      fields with respect to the percentage volume of the femoral heads receiving > 50%
      of the prescribed dose compared with three fields. There was a similar advantage
      for six (p = 0.0007) and eight (p = 0.0001) fields compared with four fields.
      Ranking of the treatment techniques indicates that the four-field technique is
      the worst with respect to femoral head irradiation but the best with respect to
      reducing rectal irradiation. A higher dose can be prescribed to the isocentre
      with the four-field technique for a 5% rectal NTCP. The six-field technique led
      to sparing of the bladder when the different treatment techniques were ranked
      using bladder dose-volume histogram data. We conclude that none of the techniques
      studied consistently proved to be superior when applied to this sample of
      patients with prostate cancer with respect to sparing all the organs at risk. The
      absolute differences between techniques are small and would be very difficult to
      detect with respect to clinically relevant endpoints.

PMID- 8539455
TI  - Prostate motion during standard radiotherapy as assessed by fiducial markers.
AB  - From November 1993 to August 1994, 55 patients with localized prostate carcinoma
      had three gold seeds placed in the prostate under transrectal ultrasound guidance
      prior to the start of radiotherapy in order to track prostate motion. Patients
      had a planning CT scan before initial simulation and again at about 40 Gy, just
      prior to simulation of a field reduction. Seed position relative to fixed bony
      landmarks (pubic symphysis and both ischial tuberosities) was digitized from each
      pair of orthogonal films from the initial and boost simulation using the
      Nucletron brachytherapy planning system. Vector analysis was performed to rule
      out the possibility of independent seed migration within the prostate between the
      time of initial and boost simulation. Prostate motion was seen in the posterior
      (mean: 0.56 cm; SD: 0.41 cm) and inferior directions (mean: 0.59 cm; SD: 0.45
      cm). The base of the prostate was displaced more than 1 cm posteriorly in 30% of
      patients and in 11% in the inferior direction. Prostate position is related to
      rectal and bladder filling. Distension of these organs displaces the prostate in
      an anterosuperior direction, with lesser degrees of filling allowing the prostate
      to move posteriorly and inferiorly. Conformal therapy planning must take this
      motion into consideration. Changes in prostate position of this magnitude
      preclude the use of standard margins.

PMID- 8539457
TI  - Daily dosimetric quality control of the MM50 Racetrack Microtron using an
      electronic portal imaging device.
AB  - The MM50 Racetrack Microtron, suited for advanced three-dimensional conformal
      radiotherapy techniques, is a complex machine in various respects. Therefore, for
      a number of gantry angles, daily quality control of the absolute output and
      fluence profiles of the scanned beams are mandatory. For the applied photon
      beams, a fast method for these daily checks, based on dosimetric measurements
      with the Philips SRI-100 Electronic Portal Imaging Device (EPID), has been
      developed and tested. Open beams are checked for four different gantry angles;
      for gantry angle 0, a wedged field is checked as well. Performing and analyzing
      the measurements takes about 10 min. The applied EPID has favourable
      characteristics for dosimetric quality control measurements: absolute output
      measurements reproduce within 0.5% (1 SD) and the reproducibility of relative
      (2D) beam profile measurements is 0.2% (1 SD). The day-to-day sensitivity
      stability over a period of one month is 0.6% (1 SD). Measured grey scale values
      are within 0.2% linear with the applied dose. The 2D fluence profile of the 25 MV
      photon beam of the MM50 is very stable in time: during a period of 5 months a
      maximum fluctuation of 2.2% has been observed. Once, a deviation in the cGy/MU
      value of 6% was detected. There is no interlock in the MM50-system that would
      have prevented patient treatment with this strongly deviating output. Based on
      the results of this study and on clinical requirements regarding acceptability of
      deviations of beam characteristics, a protocol has been developed including
      action levels for additional investigations and, if necessary, adjustment of the
      beam characteristics.

PMID- 8539456
TI  - Design of compensators for breast radiotherapy using electronic portal imaging.
AB  - A novel method of designing intensity modulated beams (IMBs) to achieve
      compensation in external beam radiotherapy of the breast, without the need for CT
      scans, is presented. The design method comprises three parts: (1) an electronic
      portal image is used to generate a map of radiological thickness; (2) this map is
      then used to obtain an estimate of the breast and lung outline; (3) a TMR-based
      dose calculation algorithm is then used to determine the optimum beam profile to
      achieve the best dose distribution. The dose distributions calculated for IMBs
      were compared with those calculated for the use of simple wedges. The results for
      two patients studied indicate that the dose inhomogeneity for IMBs is +/- 5%,
      compared with a value of +/- 10% for a wedged plan. The uncertainty in
      radiological thickness measurement corresponds to a dosimetric error of +/- 2%.
      Other errors associated with outline estimation are typically less than 2%, with
      a largest value of +5% for one of the patients who had a large and highly
      asymmetrical breast. The results for the two patients studied suggest that the
      uncertainties in the method are significantly smaller than the improvement in
      dose uniformity produced.

PMID- 8539458
TI  - Multileaf collimation versus conventional shielding blocks: a time and motion
      study of beam shaping in radiotherapy.
AB  - The work processes for the planning and delivery of shaped beams using a Philips
      multileaf collimator were studied for two treatment techniques and compared to
      those for conventional shielding blocks. The MLC proved faster in all cases of
      treatment delivery providing time reductions of 19-48% for parallel opposed beams
      and 6-44% for conformal isocentric beams. The workload in the mould room and
      workshop would be reduced if multileaf collimation is used. Time spent
      manufacturing and mounting blocks (average 2 h 30 min and 37 min, respectively)
      is eliminated for the techniques studied. The physics process for generating
      conformal MLC beams proved faster (average 1 h 36 min) than for blocks (average 2
      h 30 min); this was not so for parallel opposed beams. Overall the results
      suggest that using the MLC is a time- and resource-saving alternative to blocks.

PMID- 8539459
TI  - The impact of 3-D radiotherapy planning after a pneumonectomy compared to a
      conventional treatment set-up.
AB  - Three-dimensional radiotherapy planning (3-D RTP) is becoming more available in
      clinical practice, although so far there is little data showing its clinical
      advantage. The goal of this study was to compare 3-D RTP and dose delivery with
      conventional treatment planning in pneumonected lung cancer patients, receiving
      postoperative irradiation. Adjuvant radiotherapy in 20 pneumonected patients was
      planned with a 3-D system and patients were irradiated according to this plan.
      The resulting dose distribution was compared with the combination of a simulator
      and 2-D planned treatment to the same target volume. Dose volume histograms of
      the target, the lung and the heart of both treatment plans were analysed. A
      biophysical model was added to estimate the differences in the biological effect.
      3-D RTP significantly reduced the mean dose to the lung in 14/20 patients and to
      the heart in 20/20 patients. The mean dose delivered to the target was equal in
      both planning methods. The early clinical results do not differ from published
      results in postoperatively treated lung cancer patients.

PMID- 8539460
TI  - A concave tray with divergent block for desired dose distribution around shielded
      region in megavoltage radiation therapy.
AB  - In clinical situations large numbers of rectangular divergent blocks are required
      at different off-axis positions from central axis to shield sensitive organs.
      Superiority of divergent blocks over non-divergent blocks on a flat tray lies in
      improving the dose homogeneity. A method has been developed to minimize the
      number of divergent shielding blocks by using a concave tray at the collimator.
      The results of use of a single divergent block are similar to that of the use of
      several divergent blocks, each to match at different off-axis positions in the
      radiation beam. This type of single concave tray thus provides a considerable
      ease of handling divergent blocks in a busy radiotherapy centre.

PMID- 8539461
TI  - Limitations of a pencil beam approach to photon dose calculations in the head and
      neck region.
AB  - The inherent limitations of a specific pencil beam model have been studied when
      applied to a cylindrical geometry simulating the neck region. A comparison is
      made between measured and calculated absorbed dose in a cylindrical phantom. The
      goal is to quantify the deviations in the absorbed dose level, i.e., the dose per
      monitor unit, when photons are used for the treatment of head and neck tumours.
      Square fields ranging from 5 x 5 up to 30 x 30 cm2 are studied for photon beam
      energies of 60Co, 4, 6 and 18 MV. Ionisation chamber measurements have been
      performed in the cylinder as well as in two other configurations in order to
      trace the origin of possible deviations. For 18 MV no significant deviations are
      found between measurement and calculation in the cylindrical configuration. For
      the lower energies, an overestimation of the calculated dose in the cylindrical
      configuration up to about 6% for a 20 x 20-cm2 60Co field has been found. These
      deviations have been traced to the basic approximation for the integration volume
      for phantom scatter calculations inherent in this pencil beam implementation.

PMID- 8539462
TI  - 3rd Biennial ESTRO meeting on Physics in Clinical Radiotherapy. Gardone Riviera,
      Italy, 8-11 October 1995. Abstracts.

PMID- 8539463
TI  - [Gastrointestinal lymphomas].
AB  - Non-Hodgkin lymphomas affecting extranodal tissues can be primitive or secondary.
      The area most frequently involved is the gastrointestinal tract. MALT-type
      lymphomas are B-cell lymphomas characterized by small cells originating from the
      lymphoid tissue of the mucosa. The criteria for a correct diagnosis of extranodal
      lymphomas are morphological, but include immunophenotypic and immunogenotypic
      analysis. Gastrointestinal lymphomas consist of B-cell and T-cell lymphomas. B
      cell-lymphomas include: small cell B-lymphomas, large cell B-lymphomas,
      immunoproliferative small intestinal disease; multiple lymphomatous polyposis,
      follicular lymphomas, B-cell lymphomas centrocytic type. T-cell lymphomas include
      enteropathy-associated and non enteropathy-associated lymphomas.

PMID- 8539465
TI  - [Nosography of intestinal lymphomas].
AB  - Lymphomas can be localized to the gastrointestinal tract and can be primitive or
      secondary to a systemic lymphoma. Lymphomas can be classified as Hodgkin's and
      non-Hodgkin's. The latter include IPSID (all of the B-cell) and non-IPSID
      lymphomas. The involvement of the small intestine in its entire length is a
      feature of IPSID lymphomas. Non-IPSID lymphomas include MALT-type, which is a B
      cell lymphoma, and EATCL, a T-cell lymphoma which is a not infrequent
      complication of coeliac disease. There are several classifications of lymphomas:
      the one by Isaacson is the most widely used at present.

PMID- 8539464
TI  - [Primary lymphomas of the gastrointestinal tract: clinical picture].
AB  - Approximately 5% of all lymphomas are located in the gastrointestinal tract.
      These lesions may be secondary manifestations of systemic lymphomatous disease,
      but there are also primary lesions that are not associated with superficial lymph
      node enlargement mediastinal adenopathy, liver and spleen involvement or
      hematologic alterations. Primary lymphomas may arise in the stomach or intestine.
      Small intestinal lesions may or may not be preceded by other types of intestinal
      pathology, such as celiac or inflammatory disease. The former cases are
      characterized by persistent diarrhea, malabsorption and weight loss. Abdominal
      pain and later nausea and/or vomiting are the most common presenting symptoms of
      lesions that arise in an already diseased bowel, palpable abdominal masses are
      present in approximately one third of these cases. Gastric lymphomas often
      presents with non-specific symptoms: cramp-like epigastric pain, anorexia and
      weight loss.

PMID- 8539466
TI  - Primary gastric lymphoma.
AB  - Primary gastric lymphoma is the most frequent non-Hodgkin's lymphoma (NHL) of
      extranodal origin (25%). It accounts for 5% of all NHL and 4% of primary gastric
      malignancies. Recent studies suggest its origin from B-cell immune system. The
      majority of these tumors are high-grade centroblastic and immunoblastic subtype.
      The extent of disease is by far the most important guide to prognosis. Patients
      with gastric lymphoma usually recur in the gastrointestinal tract, but one-half
      of those recurring in abdomen also have tumor spread to extra-abdominal sites.
      Gastrectomy as a single treatment modality cures about one-third of patients with
      gastric lymphoma. The role of adjuvant therapy both in terms of radiotherapy and
      chemotherapy is not sufficiently known. In advanced stage when chemotherapy is
      indicated, CHOP combination seems to be appropriate in favorable prognostic
      situation, whereas aggressive third-generation combinations should be used for
      unfavorable cases.

PMID- 8539467
TI  - [Intestinal malabsorption, celiac disease and associated lymphoma: from symptoms
      to diagnosis].
AB  - The clinical consequences of intestinal malabsorption are extremely variable and
      a dissociation between malabsorption, malabsorption syndrome and enteropathy is
      often noted. Enteropathy does not always results in malabsorption and in an
      alteration of the tests exploring the absorptive function. The following have
      particular relevance in clinical practice: coeliac disease, malabsorption induced
      by microbiologic agent (including Whipple's disease), post-surgical malabsorption
      and selective carbohydrate malabsorption. In particular, coeliac disease has been
      analyzed in its various aspects, from studies with organ cultures to
      immunological hypotheses, from the classical variety to subclinical forms and to
      serious complications, such as enteropathy-associated T cell lymphoma.
      Malabsorption syndromes are dramatically underdiagnosed: in the typical case of
      coeliac disease, enteropathy represents a clinical iceberg, and the discovery of
      the submerged portion, represented by the polymorphous subclinical varieties, has
      just started. As far as intestinal malabsorption is concerned, the main clinical
      problem regards diagnosis.

PMID- 8539468
TI  - [Procedures for staging primary gastrointestinal lymphoma].
AB  - The non-Hodgkin's lymphomas (NHL) are usually generalized diseases and can
      involve almost any organ or tissue. Nevertheless also primary extranodal disease
      is frequent in NHL and some localizations are accomplished by a worse prognosis
      (brain, testicle) other, in particular primary gastrointestinal involvement, can
      be cured in a high percentage of cases with surgery, chemotherapy and
      radiotherapy. The gastrointestinal localization's symptomatology is not
      characteristic: abdominal pain is frequent and other symptoms can be present in
      other gastrointestinal diseases. Endoscopy, radiology and surgery are the most
      important diagnostic procedures. The first gives important information about the
      disease and it permits pre-operative diagnosis. The second is useful to detect
      both nodal extension (CT scan and MRI imaging) and intrinsic stomach or bowel
      involvement (contrast radiology of the gastrointestinal tract). The third is an
      important diagnostic and therapeutic moment. Some Authors recently don't agree
      with this invasive procedures routinely because of its potential morbidity and
      mortality. The determination of the extent of disease in patients with NHL is
      very important and serves multiple purposes: information regarding the imminence
      of potential complications, indication of prognosis and treatment planning. The
      most used staging system is the Ann Arbor scheme, originally designed for HG
      disease. This scheme is inadequate in particular for primary gastrointestinal
      NHL. Others, like Blackledge or Mushoff schemes show more correlation between
      tumor burden, nodal and extranodal involvement. An exact diagnosis, precise
      staging and a correct treatment bring to a potential curability.

PMID- 8539469
TI  - [The role of ultrasonography in the diagnosis and staging of gastroenteric
      lymphoma].
AB  - Ultrasonography (US) plays an important role in the diagnosis, staging and follow
      up of gastrointestinal lymphomas particularly when associated with complementary
      techniques such as echo-guided biopsy and endoscopic ultrasonography. Besides the
      well-known ultrasonographic "pseudo-kidney" image as sign of gastrointestinal
      pathology, the "spoke wheel" image is suggestive of gastroenteric lymphoma. This
      lesion is due to the lymphomatous infiltration of intestinal wall that looks
      ipoechoic compared to the iperechoic lumen. An early abdominal US study performed
      after clinical suspicion, should allow a presumptive identification of the
      enteric tract involved on the basis of the relationship between the
      "pseudokidney" image and the other abdominal organs. US study of the abdomen may
      be useful also to demonstrate enlarged retroperitoneal or visceral lymph nodes
      both in primary gastroenteric or systemic lymphomas. Fine needle biopsy (FNB) of
      deep lymph nodes is mandatory when superficial enlarged lymph nodes are not found
      showing a specificity and sensitivity of 100% and 66% respectively. The typical
      image of gastric wall on endoscopic US is constituted of five layers; the second
      one represents the lamina propria with the lymphatic tissue. The thickness
      increase of this layer suggest the diagnosis of gastric lymphoma. Therefore the
      endoscopic US examination is particularly important when the endoscopic features
      and the endoscopic biopsies are negative. Finally endoscopic US may be used to
      guide FNB of gastrointestinal tract lesions.

PMID- 8539470
TI  - [Gastric lymphoma: diagnostic radiology in the staging of the disease].
AB  - In the staging of gastric lymphoma, the radiologist has very important role,
      because he has many means to define correctly the stage. Conventional radiology
      is useful for detection of the lesion. Moreover, Ultrasound, Computed Tomography,
      and Magnetic Resonance are useful to define parietal extension and eventual nodal
      involvement. Lymphography remains a study kept to negative or doubt cases. In the
      future, the Magnetic Resonance will have a bigger role than now, in the
      definition of abdominal and pelvis nodal involvement.

PMID- 8539471
TI  - [Treatment of gastrointestinal non-Hodgkin's lymphoma].
AB  - Primary gastrointestinal Lymphoma is a relatively infrequent tumor, who could be
      effectively treated with both surgery and chemotherapy or radiotherapy. The
      design of treatment depends on prognostic factors, namely stage and histologic
      grade. The most functional staging system seems that of Mushoff, while the recent
      concept of "Mucosa-associated lymphoid tissue" has allowed to correlate the
      histologic grading with prognosis. Surgery is the most used therapeutic approach
      in IE and IIE stages, but both chemotherapy and radiotherapy or their combination
      seem to have similar activity. Adjuvant chemo- and/or radio-therapy after surgery
      increases survival compared to surgery alone. Chemotherapy is the treatment of
      choice in more advanced stages.

PMID- 8539472
TI  - [XXXI National Congress of the Spanish Society of Cardiology. La Coruna, 18-21
      October 1995. Abstracts].

PMID- 8539473
TI  - [Report on long-term hemofiltration in the treatment of end-stage renal failure].
AB  - Thirteen uraemic patients in chronic hemofiltration was studied over a 37.3 +/-
      25.4 months period. Hemofiltration value in long-term treatment of uraemia was
      verified by: dialytic adequacy, clinical data, complications, drop-out morbidity
      and survival. Our experience indicates that hemofiltration and especially high
      efficiency hemofiltration is an effective and soft therapy for substitutive long
      term treatment in high risk patients.

PMID- 8539474
TI  - [Plasma, erythrocyte and platelet magnesium in essential hyperTension, diabetes
      mellitus without and with macrovascular complications and atherosclerotic
      vascular disease].
AB  - In 4 groups of subjects with different clinical conditions: essential
      hypertension, diabetes mellitus without and with macrovascular complications,
      vascular atherosclerotic disease (VAD), we evaluated the plasma, erythrocyte and
      platelet magnesium content, the correlations between them and the relationships
      among all these parameters and metabolic and haemodynamic determinants. From the
      obtained data, it is evident that platelet magnesium content is decreased in
      hypertensives and in type 2 diabetics with macrovascular complications, and in
      subjects with VAD, while the red cell magnesium content in VAD subjects and in
      type 2 diabetics with macrovascular complications is increased; in type 1
      diabetics we observed a decrease of the plasma magnesium level. The relationships
      between the plasma and cellular magnesium content, in the different clinical
      conditions, seem interesting.

PMID- 8539475
TI  - [Surgery of abdominal aortic aneurysms in octogenarians. Critical remarks on
      indications for surgical intervention in different age groups].
AB  - Following the increased frequency of surgery for aortic abdominal aneurysm, due
      to increasing population age and to improved surgical and anaesthesiological
      techniques, results in octogenarians are presented and compared. The analysed
      data derive from 809 consecutive patients operated between January 1987 and
      December 1993. These have been divided into three age groups: group A = under 65
      years, group B = from 65 to 79, group C = from 80 to 93. For each group surgery
      has been divided in planned operations (symptomatic and asymptomatic cases) and
      emergency operations (performed after aneurysm rupture) and results are compared.
      Surgery has been performed as an emergency in 8.6% of cases of group A, in 18.4%
      of group B and in 41.3% of cases of group C. Death rate in the three groups was
      respectively of 1.78%, 1.90% and 4.68% for planned operations and 12.50%, 32.63%
      and 46.67% for the emergency operations. These data confirm the experience of
      other Authors and indicate that age factor must not be considered a
      controindication for planned surgery. The importance of this factor in emergency
      surgery, the greater frequency of ruptures with increased age and the quality of
      the results in planned surgery suggest a widening of the indications for surgery:
      the aneurysm transverse diameter of 5 cm, as a minimal measure for planned
      surgery, must be reconsidered.

PMID- 8539476
TI  - POEMS syndrome in a female Italian patient. A case report.
AB  - POEMS syndrome is an uncommon association of polyneuropathy, organomegaly (liver,
      spleen, lymph nodes), endocrinopathy (hypogonadism primary hypothyroidism,
      diabetes mellitus, adrenal insufficiency), monoclonal gammopathy and skin
      changes; bone lesions (generally osteosclerotic, less frequently osteolytic or
      mixed) are nearly always present in this multisystem disease. We describe the
      first case of a female Italian patient with POEMS syndrome. Therapy with
      prednisone was of scant benefit and the patient died of cardiogenic shock some
      days after temporary pacemaker implantation, performed for recurrent episodes of
      bradycardia. From the beginning of steroid therapy she survived about fifteen
      months.

PMID- 8539477
TI  - Benign recurrent intrahepatic cholestasis. Some reflections on a case followed
      for 20 years.
AB  - Benign recurrent intrahepatic cholestasis (BRIC) is a form of cholestasis of
      obscure aetiology characterized by recurrent episodes of jaundice and itching
      associated with a morphological picture of pure intrahepatic cholestasis. No
      effective treatment has yet been found among the many that have been proposed and
      the invariably benign nature of the condition has been questioned. A case of BRIC
      followed for a period of 20 years is described. This case is of great interest
      from these two points of view: 1) the histologic and electron microscopic
      findings 23 and 41 years after the first episode of cholestasis, respectively,
      failed to reveal evidence of the possible future development of cirrhosis; 2)
      treatment with ursodeoxycholic acid proved ineffective both therapeutically and
      in the prevention of episodes of bile stasis: on the contrary, calculosis of the
      common bile duct appeared after 8 months from the onset of the treatment.

PMID- 8539478
TI  - [Multiple osseous avascular necrosis in a patient with systemic lupus
      erythematosus with antiphospholipid antibody positivity].

PMID- 8539479
TI  - [Prospects of medicine in 2000].

PMID- 8539480
TI  - [Guidelines for clinical practice: instructions for use].

PMID- 8539481
TI  - [Usefulness of the determination of C reactive protein and other acute phase
      proteins in rheumatoid arthritis].
AB  - The acute phase response is defined as a large number of diverse reactions which
      attempt to adjust the organism to the effects of stress/injury. It is now clear
      that there is a complex interaction between the cytokines with interleukin-6
      predominant, but also involving interleukin-1, tumor necrosis factor and a group
      of recently described cytokines including as well interleukin-11, leukaemia
      inhibitory factor and oncostatin M all of which influence the levels of acute
      phase proteins. In clinical practice, C reactive protein (CRP) is frequently used
      as marker of the acute-phase response. It has a short half-life and consequently
      it is a sensitive measure of cytokine-induced protein synthesis. In rheumatoid
      arthritis (RA) the rate appearance of bony erosions in the early phase of the
      disease correlated with the mean serum concentration of CRP in some studies. A
      recent study examining the rate of spinal trabecular bone loss in the first year
      of rheumatoid disease found a strong correlation between bone loss and serum CRP
      concentrations. It appears that CRP concentrations reflect the level of "systemic
      osteoclast-activating factor" and are, therefore, a good measure of the general
      catabolic state of the patient. Many would now consider that persistently
      elevated serum CRP in patients with RA is in itself an indication for
      immunosuppressive therapy.

PMID- 8539482
TI  - [High incidence of oxacillin-resistant Staphylococcus aureus in a general
      hospital].

PMID- 8539483
TI  - [Methemoglobin in AIDS].

PMID- 8539484
TI  - Epidemiology of hepatitis B and delta virus infection in Albania: an approach to
      universal vaccination.

PMID- 8539485
TI  - The epidemiology of hepatitis A in Italy.

PMID- 8539486
TI  - Epidemiology and prevention of hepatitis type C in Italy.
AB  - Viral hepatitis type C is of public health importance in all parts of the world.
      In Italy, hepatitis C accounts for approximately 18% of the annually reported
      cases of acute viral hepatitis. The national rate of acute non-A, non-B hepatitis
      (the majority of which are hepatitis C) has significantly decreased during the
      last decades. At present, the onset of the disease occurs more frequently in
      individuals 15-24 years old, in men more frequently than in women and in persons
      living in the south of the country. During the last 5 years the rate of
      transfusion-associated hepatitis C has dropped (4.8 cases per 1,000,000 in 1989
      versus 0.4 per 1,000,000 in 1993), while the percentage of patients who are
      intravenous drug abusers (IVDA) has increased from 18% to 33%. The high
      prevalence of anti-HCV (hepatitis C virus) antibody in blood and blood products
      recipients, IVDA and health-care workers with occupational exposure to blood
      indicates that HCV is efficiently transmitted parenterally. Data concerning
      transmission of HCV from mother to infant or by person-to-person contact, either
      by sexual or by non-sexual household contact, are controversial. However, there
      is almost universal agreement that the presence of concurrent infection with HCV
      and human immunodeficiency virus enhances the rate of vertical/perinatal HCV
      transmission as well as transmission through sexual and other types of person-to
      person contact.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539487
TI  - DNA-mediated immunization: prospects for hepatitis B vaccination.

PMID- 8539488
TI  - Virus escape from immune control: mechanisms of persistence within the host.

PMID- 8539489
TI  - Host and viral features in chronic HCV infection: relevance to interferon
      responsiveness.
AB  - Host and viral variables interact in determining the course and responsiveness to
      therapy of any viral infection. Presence of cirrhosis, serum levels of hepatitis
      C virus (HCV) RNA and the genotype of infecting virus are considered predictive
      of response to interferon (IFN) in chronic HCV infection. We evaluated these
      parameters in relation to IFN therapy in a cohort of anti-HCV-positive subjects
      with chronic hepatitis or cirrhosis. HCV RNA was detected by polymerase chain
      reaction (PCR) and by the branched DNA assay (bDNA), to quantify viraemia. HCV
      typing was performed by reverse-hybridization line probe assay. HCV RNA was
      detected in almost all anti-HCV-positive subjects with liver disease, PCR being
      more sensitive than bDNA. Hepatitis C viraemia was lowest in cirrhosis. Low
      pretreatment viraemia selected for those patients with chronic hepatitis
      obtaining a high rate of sustained response to IFN. The role of HCV type was less
      clearcut, due to the high prevalence in our population of type 1 (especially
      subtype 1b, accounting for 80% of cases). A trend towards a better response of
      non-1b genotypes was confirmed. This may be related to higher HCV RNA levels in
      type 1b-infected subjects. Cirrhosis remains however, independently from
      virological features, the strongest predictor of non-response to IFN.

PMID- 8539491
TI  - Detection of a 5' UTR variation in the HCV genome after a long-term in vitro
      infection.
AB  - The TOFE lymphoid cell line from normal human bone marrow is susceptible to
      infection by a hepatitis C virus (HCV) serum strain. A sequence analysis of the
      5' untranslated region (UTR) of HCV before and after long-term in vitro infection
      revealed one base substitution at position -158 (C > T) of the 5' UTR. We
      performed the direct sequencing of 5' UTR polymerase chain reaction-amplified
      sequences of the HCV genome: a) from the original serum-derived strain; b) from
      TOFE cell extracts 6 months post infection. This base substitution in the
      regulatory elements of the 5' UTR might be related to the ability of the virus to
      grow in cell culture.

PMID- 8539490
TI  - Viral load in samples from hepatitis C virus (HCV)-infected patients with various
      clinical conditions.
AB  - Molecular methods for the absolute quantitation of nucleic acids present in
      biological samples have recently been developed and applied in basic and in
      medical virology; these studies indicated that competitive polymerase chain
      reaction (PCR) and competitive reverse transcription PCR (cRT-PCR)-based
      methodologies are currently the methods of choice for quantifying DNA and RNA
      species present in clinical samples at low concentration. Recently, quantitative
      molecular techniques were developed to study the hepatitis C virus (HCV)
      pathogenic potential, the natural history of HCV-infected patients and the
      efficiency of antiviral therapies in real time. The pilot study reported here was
      carried out using a cRT-PCR application for the direct quantitation of HCV RNA
      molecules in plasma samples of infected individuals which was recently developed
      in our laboratory. Although sharp individual variability of viral load was
      documented in this study, the mean HCV RNA copy number detected in samples from
      untreated HCV-infected patients with various clinical conditions (chronic active
      hepatitis, cirrhosis, cryoglobulinaemia and chronic hepatitis) was substantially
      similar, with only one exception: in samples from patients tested positive for
      anti-liver-kidney microsomal (anti LKM1) auto-antibodies, a significantly lower
      HCV viraemia level was revealed. Additionally, HCV viraemia was monitored in four
      patients with sustained biochemical and histological response (at least 12
      months) following interferon-alpha discontinuation.

PMID- 8539492
TI  - Engineered liposomes and virosomes for delivery of macromolecules.
AB  - In order to utilize virosomes or proteoliposomes for the delivery of drugs or
      macromolecules to specific pathologic target cells we elaborated a system to
      shuttle drugs to solid tissue (liver) as well as to the macrophages, a crucial
      cellular compartment of the immune system. Using virosomes prepared from the
      P3HR1 strain of Epstein-Barr virus, we demonstrated that these particles fused
      with human hepatocarcinoma cell line Li7A and therefore might be used as drug
      vectors. Furthermore, we report that proteoliposomes prepared by reconstituting
      in a cocktail of phosphatidylserine-phosphatidylcholine the anion transporter
      band 3 protein markedly increased the phagocytic activity of macrophages in
      culture. This could represent a new device to be used as a drug delivery system
      to enhance specific macrophagic functions.

PMID- 8539493
TI  - Fusion of EBV with the surface of receptor-negative human hepatoma cell line Li7A
      permits virus penetration and infection.
AB  - Our preliminary data suggest that Epstein-Barr virus (EBV) is able to bind to and
      fuse with the surface membranes of hepatoma cell line Li7A. In order to obtain
      further evidence, we utilized the relief of rhodamine fluorescence to monitor
      whether fusion would also take place when Li7A cells were exposed to experimental
      conditions such as neutral or low pH. It is well known that for some viruses,
      protonation in the endosomal compartment is needed to trigger the fusion. We
      show, furthermore, that the rate and extent of fusion are not affected by
      pretreatment of the cells with agents known to elevate the lysosomal and
      ensodomal pH, such as chloroquine or NH4Cl (lysosomotropic agent). By indirect
      immunofluorescence assay, in addition, we confirmed the binding of the EBV to the
      Li7A cell surface membrane. We attempted finally to correlate the above processes
      with successful infection of Li7A cells by EBV detected using the polymerase
      chain reaction technique. In spite of the apparent lack of viral receptor CD21,
      these nonlymphoid cells appeared susceptible to EBV penetration and infection
      through fusion with the plasma membrane at the surface of the cells.

PMID- 8539494
TI  - Role of Akata cell membrane fluidity in susceptibility to Epstein-Barr virus
      infection.
AB  - Infection by Epstein-Barr virus (EBV), a B lymphotropic human herpesvirus, of its
      target cells is initiated by the binding of the viral envelope glycoprotein
      gp350/220 to a 145-kDa cell membrane glycoprotein (CD21, CR2) which also serves
      as the receptor for the complement fragment C3d (Fingeroth et al., 1984; Nemerow
      et al., 1987). We used the fluorescent probe 1-6-diphenyl-1,3,5-hexatriene (DPH),
      extremely sensitive to the polar environment, in order to analyse the membrane
      viscosity distribution in single cells of two lymphoid cell lines, Raji and
      Akata. Lipid analysis on both cell lines showed a slightly lower
      cholesterol:phospholipid molar ratio on Akata than on Raji cells. Measurements of
      cell fluidity by DPH polarization in native cells and after cholesterol
      enrichment indicated that the apparent Akata membrane viscosity was lower than
      the viscosity of Raji cells. To examine the possibility that this difference
      could be correlated to a difference in the behaviour of Akata and Raji cells in
      expressing EBV early antigens, both lines were superinfected with the EBV non
      transforming P3HR1 strain. We report here evidence that lipid composition can
      regulate EBV entry into cells.

PMID- 8539495
TI  - [What is your diagnosis? Cystic fibrosis].

PMID- 8539496
TI  - [Progress in neurology in the 20th century].

PMID- 8539497
TI  - [Social change and sciences in the 20th century].
AB  - The symbiotic interdependence of state, economy and science is one of the most
      significant structural characteristics of the 20th century. This development
      results from inherent scientific as well as from social procedures and needs, and
      it has been favoured by the two World Wars, culminating in the Cold War. This led
      to new structures: institutions of large scale research, think tanks, and the
      military-industrial complex. Big government, big business, and big science are
      depending on each other. Parallel to the new way of thinking in physics
      (Einstein, Bohr and others), finally accomplished by the revolution in
      cybernetics (Wiener), the traditional borders between disciplines have been
      overcome. The production of new knowledge is now of primary importance. Today,
      information proves to be one of the strategic resources which determines
      prosperity, power and prestige as well as success in economic and political
      markets.

PMID- 8539498
TI  - [The doctrine of brain localization and its development in the 20th century].
AB  - The discovery of the cerebral motor cortex in the last third of the 19th century
      has decisively influenced the doctrine of cerebral localization. It has dominated
      brain research from there on. Its considerable practical importance for focalized
      local diagnosis was recognized from the clinical point of view. As a consequence,
      interdisciplinary institutions for brain research developed in Europe and in the
      USA for the study of functional localization in the brain by means of cyto- and
      myeloarchitecture, electrical brain stimulation and lesion experiments in close
      connection with clinico-neurologic centers. From this research resulted the
      cerebral cortical maps with more or less numerous areas linked to either sensory,
      motor or 'higher' psychic functions. An intensive, emotional critique developed
      against the brain-localization theory from its onset. This article demonstrates
      that the arguments of the anti-localizationists gave rise in part to new
      knowledge about some principles of cerebral function. Some of these are the
      concept of 'diaschisis' (distant effects of acute lesions and functional
      recovery, von Monakow, 1902), the concept of 'motor equivalence' (Lashley, 1930)
      and of neuronal plasticity of the cerebral cortex (Cajal, 1911). Furthermore,
      modern imaging techniques (position emission tomography, functional nuclear spin
      resonance) show that complex functions in particular, such as the natural,
      targeted arm and grasp synergy, are not 'localized' within a small area of the
      cortex but do activate multiple neuronal networks interconnected dynamically and
      in alternating composition in the process of movement initiation and execution.

PMID- 8539499
TI  - [Neurology at the threshold of the 21st century].
AB  - In the controversial field of a continuously changing neurology with the problem
      of rising medical costs, the perspectives of modern neurology at the beginning of
      a new century are described by four aspects: 1. Relatively new are the studies of
      neuropsychiatric symptoms in neurologic diseases. An immediate diagnosis and
      treatment of these symptoms can improve the outcome of the neurologic disease. 2.
      An example for the progress in investigative methods by medical technology is
      magnetic resonance imaging which allows a more refined diagnosis and which
      improves and reevaluates the importance of the clinical examination. There is a
      warning on the other hand about unnecessary and badly planned examinations. 3.
      Advances in clinical neurology are mentioned by describing neurogenetic diseases,
      infectious neurologic diseases and new forms of dementia. 4. Some therapeutical
      aspects concerning neuroprotection and neurologic intensive care are discussed.
      Finally, the aims for the training of future neurologists are briefly outlined.

PMID- 8539500
TI  - [Electroencephalography and epileptology in the 20th century].
AB  - In 1875, Caton was already able to detect cerebral electric currents during
      experimental studies in animals. In 1914, Cybulski and Jelenska-Macieszyna
      reported on the increase of current-intensity during a focal motor epileptic
      seizure. In 1929 in Jena, Berger revolutionized the study of epilepsy with his
      paper on the human electroencephalogram 'Uber das Elektrenkephalogramm des
      Menschen'. His discovery and further publications as well as later works of
      numerous researchers, especially F. and E. Gibbs, Lennox, Penfield and Jasper,
      made it possible to distinguish different forms of 'little' epileptic seizures
      and to separate them from nonepileptic paroxysmal disorders. New epileptic
      syndromes could be singled out, as e.g. the symptomatic epilepsy of childhood
      with variable clinical manifestations of seizures and slow spike-wave complexes
      in the EEG (Lennox-Gastaut syndrome) or the benign partial epilepsy of childhood
      with centrotemporal EEG spikes. In these fields, as well as for the epileptic
      seizures in newborns and babies and for the differentiation between epileptic and
      nonepileptic twilight states in later stages of life, the EEG remains an
      indispensable tool in the CT and MRI era. It also contributes largely to the
      diagnosis of nonepileptic cerebral illness such as herpes simplex encephalitis,
      subacute sclerosing panencephalitis van Bogaert and Creutzfeldt-Jakob disease.
      Since the introduction of phenobarbital by Hauptmann in 1912, the palet of
      effective drugs against epilepsy, such as phenytoin, carbamazepine, valproate and
      benzodiazepines used for status-epilepticus treatment, became essentially larger.
      The value of newer substances (vigabatrin, progabide, gabapentin, lamotrigin)
      can't be estimated actually.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539501
TI  - [The history of sleep research in the 20th century].
AB  - Not until the 19th century theories on sleep were based upon experimental
      findings in animal and humans. The so-called 'hypnotoxin theory' culminated, when
      Legendre and Pieron successfully induced sleep in a dog by transmission of
      cerebrospinal fluid from a dog deprived of sleep. The main discussion concerning
      the origin of sleep has been the question if sleep is a passive or an active
      state. Similarities with coma, the positive Babinski sign and pathoanatomical
      findings in patients who died after encephalitis lethargica were the arguments
      for the 'deafferentiation hypothesis'. Bremer's classical brainstem-transsections
      in cats confirmed this idea. Pavlov was the major representative of the idea that
      sleep was due to a general inhibition of the brain. Hess induced physiological
      sleep in cats by electrical stimulation of the diencephalon, proving the active
      nature of sleep. The introduction of the EEG in animals by Caton and in humans by
      Berger allowed for the first time the measurement of sleep depth without waking
      the sleeper. After discovery of the REM sleep periods by Aserinsky and Kleitman
      in 1953 and the demonstration of periodical sleep cycles by Dement and Kleitman,
      polysomnography with simultaneous whole night recording of EEG, EMG,
      electrooculogram and other physiological parameters was established as the major
      diagnostic tool in sleep disorders. One of the most important questions about the
      function of sleep is still unresolved. NREM sleep is believed to have a
      restorative function, whereas REM sleep might be involved in learning processes.
      According to the sleep interpretation of Sigmund Freud, the dream content
      represents endogenous wishes which cannot be expressed during wakefulness because
      of an internal 'sensor'. A more recent theory by Hobson explains the dreams by a
      very unspecific brainstem activity occurring during REM sleep which projects to
      the frontal brain and activates stored memory. The most important sleep disease
      of the 20th century is certainly the sleep-apnea syndrome. Charles Dickens
      described in his 'Pickwick Papers' subjects with this illness already 150 years
      ago. The pathogenetic significance of the apneas during sleep, however, were
      recognized in 1965 only by Gastaut and at the same time by Jung and Kuhlo.
      Treatment for insomniacs was restricted for many years to alcohol, opium and
      barbiturates. Following the horrible sequelae of thalidomide therapy in 1956, a
      more efficient treatment was available through the introduction of
      benzodiazepines after 1960.

PMID- 8539502
TI  - [The history of clinical neurophysiology in the 20th century].
AB  - The history of clinical application of electromyographic and electroneurographic
      techniques is not even 60 years old. For a long time the clinicians' need could
      not be fulfilled, due to the imperfection of the electronic equipment. Nowadays,
      electromyography and electroneurography are established methods not only for the
      diagnosis of neuromuscular disorders, but since the recording of cortical and
      spinal evoked potentials has been introduced, diseases of the central nervous
      system lie also within its scope.

PMID- 8539503
TI  - [Neuroradiology--past and future].
AB  - After the discovery of X-rays by Roentgen exactly 100 years ago, neurosurgeons
      and neurologists have been promoting an imaging diagnosis of the central nervous
      system around the turn of the century with methods like pneumencephalography and
      angiography. With the induction of computed tomography and magnetic resonance
      imaging (MRI) in the last two decades, seemingly simple examination methods
      became available which led to a temporary separation of neuroradiology from its
      parent fields. Further development of MRI with methods that allow to measure
      brain perfusion and to visualize brain function has led this diagnostic modality
      back to its origin, neurology: adequate evaluation of such multimodality imaging
      is only possible in the context of all neurosciences. On the other hand,
      interventional neuroradiology with endovascular procedures in the brain has
      evolved to an operative field that is only feasible in close cooperation with
      neurosurgery. This also applies to MRI, where the 'open magnets' require close
      cooperation between neuroradiologist and neurosurgeon to perform image guided
      procedures online.

PMID- 8539504
TI  - [Neuropsychiatry and neuropsychology].
AB  - The 17th centurys origins of neuropsychiatry are found in the works of Thomas
      Willis, who introduced the terms 'psychologia' and 'neurologia' and developed a
      complete neuropsychiatric concept. His views were revived by 18th-century
      animists and vitalists who were able to accept body-mind interactions, unlike the
      followers of Leibniz (e.g. Haller) who stuck to his psychophysical parallelism
      without possible interaction. This was also the creed of John Hughlings Jackson,
      whose influence on the development of neuropsychiatry and neuropsychology in the
      first decades of the 20th century was second to none. Neuropsychiatry, a Germanic
      specialty, was able to germinate in 1845 in Griesinger's 'Pathology and therapy
      of mental diseases', after Gall, Mesmer, Johannes Muller and many others had
      reformed and expanded the concept of mind-body interaction. In the second half of
      the 19th century, in the German-speaking countries progress in both neurology and
      psychiatry was usually achieved by neuro-psychiatrists. Neuropsychology (Lashley,
      1913) was a product of both Jacksonian and Germanic neuropsychiatric ideas.
      During the 20th century neurology was separated from psychiatry, but new trends
      and their names such as 'psychobiology' and 'biological psychiatry', although
      quite old, are suggestive of a new kind of neuropsychiatry.

PMID- 8539505
TI  - [Critical study of the characterization of hyperandrogenism in a group of obese
      women].
AB  - The authors report the hormonologic characteristics of 20 obese and hirsute women
      meeting the criteria for adrenaltype hyperandrogenism, suppressible by
      dexamethasone, without hyperprolactinemia and without any late developing partial
      enzyme block appearance. The laboratory profile of these women differed from that
      of a group of women with type 1 polycystic ovaries syndrome. In this same group
      obese women in whom LH/FSH ratio was below 1, there was evidence under baseline
      conditions of a moderate increase in testosterone and delta 4-androstenedione in
      relation to increased plasma levels of DHA and SDHA, plasma delta 4 and delta 5
      androgen levels falling precipitalely during the dexamethasone suppression test.
      The ACTH stimulation test revealed greater reactivity for 17 hydroxy-pregnenolone
      (p < 0.001) and less for 21-deoxycortisol than in the control group of normal
      women (p < 0.01). The essentially adrenal origin of plasma hyperandrogenism in
      certain cases of obesity is discussed. Insulin could increase adrenal sensitivity
      to ACTH and its possible action in vivo on the activity of adrenal enzymes
      requires clarification. The accumulation of certain androgens in the adrenal
      cortex could also be responsible for dysregulation of 3 beta ol-dehydrogenase and
      11-hydroxylase.

PMID- 8539506
TI  - [Laparoscopic surgery of an intraperitoneal intrauterine device].
AB  - This study involved 13 cases of patients fitted with intra-uterine contraceptive
      devices which migrated in the abdominal cavity. Laparoscopy enabled localization
      of the IUCD and full lesion assessment. It was removed by celio-surgery in all 13
      cases. Difficulties encountered were due to parietoepiploic adhesions and IUCD
      impacted in the wall of the rectum.

PMID- 8539507
TI  - [Amniocentesis and single choroid plexus cyst. Current status].
AB  - Management of a patient with a diagnosed choroid plexus cyst (CPC) is probably
      one of the most difficult of all prenatal diagnostic problems. Similarity between
      the risk of chromosomopathy due to the appearance of CPC only and the risk of
      fetal mortality due to amniocentesis (both being about 1/200) is such that an
      individual approach must be adopted in each case. The couple must be given a full
      explanation of all the details, which will enable them to finally decide whether
      a conservative attitude is appropriate or, on the contrary, if a specific
      diagnosis should be sought by amniocentesis.

PMID- 8539508
TI  - [Possible implication of obstetric risk factors in the etiopathogenesis of
      schizophrenia].
AB  - Neuroradiologic and neuropathologic studies have revealed evidence of the
      existence of structural brain damage in schizophrenics, the ethiopathogenesis of
      which could include early neurodevelopmental disturbances. Exposure to obstetric
      complications could be an environmental risk factor predisposing to the later
      occurrence of schizophrenic disorder in adolescence. The majority of studies
      evaluating such an association have found an excess of obstetric complications in
      schizophrenia patients, tough without revealing the existence of a preferential
      link with a specific type of complications. These interpretation of these results
      in terms of cause-and-effect must remain cautious, because of the methodological
      limitations of the studies.

PMID- 8539509
TI  - [Are there still indications for cerclage in 1995?].
AB  - AIM: In order to assess their undertook a retrospective study in their department
      over a 4 year period: from January 1991 to December 1994. METHOD: the study
      concerned 129 patients who were treated by cerclage. This procedure was performed
      prophylactically in the great majority of them (97), while it was carried out as
      an emergency in 32 (25%). RESULTS: the authors drew a distinction between two
      groups (prophylactic and emergency suture) when analyzing the various results:
      complications due to suture, mean age of pregnancy at delivery, threatened
      premature labor, mean length of prolongation obtained. These personal data formed
      the basis of a review of the literature, in order to specify the indications for
      suture adopted by various authors at the present time. CONCLUSION: the authors
      found themselves to be in agreement with data from the literature, considering a
      history of at least two obstetric accidents (late abortions) and/or the existence
      of a severe uterine malformation to be the principal indication for prophylactic
      suture. "Emergency" suture should be performed whenever there is a serious threat
      of early premature labor in the presence of cervical changes such that suture
      offers the only chance of prolonging the pregnancy.

PMID- 8539510
TI  - [Peripartum hysterectomy. Report of eleven cases].
AB  - A series of hysterectomies performed during labor or shortly after delivery, all
      as emergencies is reported. The study covered the ten years 1982-1991, during
      which 65,488 deliveries resulted in infants with a birth weight of 500 g or more.
      There were no hysterectomies among the 21,998 primipara, the incidence in
      multipara being 1 per 3,954 deliveries. Five operations were performed for
      rupture of the uterus and six for cataclysmic bleeding. Seven of the 11 patients
      had history of caesarean section. In multipara, the existence of a caesarean scar
      multiplied the risk of emergency hysterectomy by a factor of 18. There were no
      maternal deaths but all patients required transfusion with more than 6 units of
      packed cells. These results emphasize the fact that a history of caesarean is the
      principal etiologic factor in patients experiencing complications of pregnancy
      which require emergency peri-partum hysterectomy.

PMID- 8539511
TI  - [Breast angiosarcoma. Five case reports].
AB  - The authors report 5 cases of breast angiosarcoma collected in the Salah Azaiz
      Institute of Tunis, the only oncology center in this country, between 1969 and
      1990. They enumerated 4,000 malignant breast tumors during this period; i.e. an
      incidence of 1.25%, higher than that in the world literature (0.4%). The mean age
      of patients was 44. Three were post-menopausal, and two were of childbearing age,
      one of whom was pregnant. This rare tumor is virtually limited to women.
      Affection is scarce, it affect's almost exclusively women. It generally present
      as a painless, ill-defined mass, without regional lymphadenopathy. The diagnosis
      of angiosarcoma is difficult since the histologic appearance is sometimes
      identical to that of a hemangioma. Hence the value of very thorough histologic
      examination of the entire operative specimen. Treatment is based upon mastectomy.
      The usefulness of adjuvant chemotherapy and/or radiotherapy is uncertain. The
      prognosis remains gloomy despite early diagnosis and treatment. The authors
      attempt in this study to identify the various features of this serious and
      uncommon condition, based upon the rare published cases in the world literature.

PMID- 8539512
TI  - [Umbilical endometriosis. A case report].
AB  - Umbilical endometriosis is a rare site of the disease. The authors report a case
      of umbilical endometriosis only. Umbilical involvement is estimated at 0.5 to 1%
      of all site of the disease. This is a disorder affecting women of childbearing
      age, with a mean age of about 40. Medical treatment by progestogens or Danazol is
      inconstantly and partially effective regarding umbilical endometriosis. Surgical
      excision remains the only effective treatment: omphalectomy with wide removal of
      the tumor and reconstruction of an umbilicus. Surgery enables histologic study
      and, in the presence of suggestive symptomatology, search for and treatment of
      other genital sites.

PMID- 8539513
TI  - [Postpartum depression: too often neglected!].

PMID- 8539514
TI  - [Education and the management of change].

PMID- 8539515
TI  - [Qualitative evaluation of primary nursing services. Perspectives of the Catalan
      Health Service].

PMID- 8539516
TI  - [Psychomotor development during the first 6 years. Measuring instrument: the
      Levant test].

PMID- 8539517
TI  - [Treatment of pressure ulcers at home. Multicenter study of a dressing made of a
      combination of carboxymethyl-cellulose and calcium alginate with hydro-regulatory
      activity].

PMID- 8539518
TI  - [Nurses get together to discuss AIDS. Quality of life, an endless search].

PMID- 8539519
TI  - [It is necessary to preserve historical records].

PMID- 8539520
TI  - [Gimbernat University schools. History of schools with varying programs].

PMID- 8539521
TI  - [Psychological motivators "COMPLACE". Effects on the selection on the selection
      of nursing].

PMID- 8539522
TI  - [Hospital associated professor. An experience].

PMID- 8539523
TI  - [Low temperature sterilization. A solution for every problem].

PMID- 8539524
TI  - [How to organize a congress. Various rules].

PMID- 8539525
TI  - [Research, in Brazil?].

PMID- 8539526
TI  - [Risk factors for cancer of the esophagus: a case control study in a metropolitan
      area of south-eastern Brazil].
AB  - The association between esophageal cancer and smoking and drinking habits,
      instruction and nutritional factors was examined by means of the utilization of
      data of a case-control study which was undertaken in the city of S. Paulo
      (Brazil). Eighty five cases were compared with two hundred and ninety two
      hospital controls, with different diseases, including other kinds of cancer. The
      crude estimations of the odds ratios were calculated for all the variables.
      Logistic regression was used in the next steps of the analysis. The drinking
      habit [odds ratio = 3.68, 95% confidence interval (1.74 - 7.78)], the smoking
      habit [odds ratio 4.86; 95% confidence interval (1.95 - 12.13)] and the frequent
      eating of hot pepper [odds ratio = 2.48; 95% confidence interval (1.46 - 4.23)]
      are important risk factors for the disease. The estimate of odds ratio for
      smoking ordinary cigarette was 3.43 (1.31-8.97) and for smoking of corn straw
      hand-rolled cigarrette was of 4.18 (1.38-12.66).

PMID- 8539527
TI  - [Industrial work and lung cancer].
AB  - In a hospital-based case-control study, 316 lung cancer cases and 536 controls
      were interviewed for their occupational, smoking, passive smoking, cancer in the
      family and residential histories as well as social economic status, by trained
      interviewers, using a standardized questionnaire. Cases and controls were matched
      by hospital, sex and age. The study was carried out between 1st July 1990 and
      31st January 1991 in 14 hospitals in the Metropolitan Region of S. Paulo, the
      most highly industrialized and urbanized region in Brazil. Score criteria were
      developed for the ordering of the individuals of the study by occupational
      exposure to know carcinogens to the lung, in order to evaluate this exposure
      during the occupational life of each person. The criteria accumulated information
      on exposure to carcinogens as regards type, sector of work and time in each
      employment. The unconditional logistic regression analysis showed an odds ratio
      of 1.97 (95% IC: 1.52 to 2.55) for the highest exposure group. This result showed
      that workers linked to the production sectors of several industries have about
      twice the risk of developing lung cancer as workers involved in non-industrial
      activities.

PMID- 8539529
TI  - [Mosquito (Diptera: Culicidae) ecology in natural and artificial breeding places
      in rural areas of the northern Parana State, Brazil. I.--Collections from a
      riverbed].
AB  - The objective of this study is to identify the Culicidae species apt to colonize
      the waters of a creek with reduced gallery forest in the southern region of
      Brazil. Captures were performed using a water insect-collecting net. The
      following species were captured. Aedes crinifer, Aedomya squamipennis, Anopheles
      fluminensis, An. intermedius, An. albitarsis, An. argyritarsis, An. evansae, An.
      strodei, An. oswaldoi, An. Triannulatus, Chagasia fajardi, Culex bidens, Cx.
      group coronator, Cx. eduardoi, Cx. Mollis, Cx. quinquefasciatus, Cx.
      coppenamensis, Cx. vaxus, Cx. group inhibitor, Cx. intrincatus, Cx.
      (Melanoconion) sp, Psorophora saeva (?) and Uranotaenia pulcherrima. As for the
      species which showed the highest frequency rate, the following aspects were
      studied: population fluctuation, environmental factor correlated with geographic
      distribution along the area. It was concluded that superficial waters with
      reduced gallery forest may serve as a refuge for some Culicidae. This fact may
      contribute to the domiciliation process of the species.

PMID- 8539528
TI  - Erythroderma: analysis of 247 cases.
AB  - The profile of 247 patients with erythroderma during a 23 year period from
      January, 1962 through March, 1985, with a follow-up period ranging from 1 to 26
      years were analysed. The patients presented with diffuse erythema, scaling and
      pruritus of more than 2 months' duration, and the age ranged from 16 to 60 years.
      Psoriasis was the most frequent underlying disease with an estimated frequency of
      44.9%, the reaction to the use of drugs appeared in 7.3% of total cases and
      association with reticulosis showed a frequency of 4.1%. The cause of the
      erythroderma could not be determined in 29.2% of the cases. Six differences in
      terms of underlying diseases were not observed. One or more skin biopsies along
      with clinical findings were diagnostic or suggestive of the underlying disease in
      63.6% of the cases. Repeated skin biopsies are recommended as the best method for
      etiologic diagnosis of erythroderma. At P = 0.05 significance level,
      masculine/feminine ratio of 2:1 was found. The question arises whether causal
      agent of erythroderma may not be somehow related to different exposure by sex to
      environmental antigens.

PMID- 8539530
TI  - [Urban ecology of Triatoma infestans in Argentina. Association between Triatoma
      infestans and pigeon cotes].
AB  - A study was undertaken in an urban area of the capital city of the province of
      San Juan, Argentina, in a housing complex of 768 flats distributed in buildings
      of 3 and 7 floors each surrounding an abandoned central winery. A total of 329
      Triatoma infestans were captured, 293 on 4 terraces of seven-floor-towers and 36
      inside the winery, associated with the greater number of pigeons which nest in
      those places. The bugs were sheltered in the dung accumulated between the cement
      blocks used to floor the terraces and inside the unused tuns in the winery. Two
      main bug foci were identified associated with the dense pigeon colonies: 81.5% of
      the T. infestans collected were found in one of the towers (4B) and 11% in the
      central winery. After six months of insecticidal spraying of the infested areas,
      those terraces in which T. infestans has not been previously found resulted gave
      positive results. The feeding profile of triatomines shows a predominance of
      simple bird blood meals; in the buildings and the winery 95% of the T. infestans
      analyzed were identified for bird blood meals; the rest had fed on one or more
      sources: human, dogs or cats. None of the T. infestans was infected by T. cruzi.

PMID- 8539531
TI  - Studies on mosquitoes (Diptera: Culicidae) and anthropic environment. 9
      Synanthropy and epidemiological vector role of Aedes scapularis in south-eastern
      Brazil.
AB  - Behaviour comparisons of Aedes scapularis and Ae. serratus are presented. Results
      were obtained by sampling Aedes adult mosquitoes at several places in the rural
      anthropic environment in the Ribeira Valley region of S. Paulo State, Brazil.
      Aedes dominance was shared by those two species, but Ae. scapularis showed a
      clear tendency to frequent the modified environment, while Ae. serratus was to be
      found in the more preserved ones, here represented by the vestigial patchy
      forests. Regarding the open cultivated land and the dwelling environments, Ae.
      scapularis preponderates. Considering the regional development phases, this
      mosquito showed a remarkable increase in the modified environment differently
      from Ae. serratus that underwent a considerable decrease in migrating from the
      forest to the anthropic environment. As a consequence of these results it is
      reasonable to conclude that Ae. scapularis may be considered as an
      epidemiologically efficient vector and that it quite probably played this role in
      the Rocio encephalitis and other arbovirus epidemics.

PMID- 8539532
TI  - [Assessment of vaccination coverage of the basic schedule for the 1st year of
      life].
AB  - Immunization coverage was evaluated in all 12-23 month-old children living in the
      area were five years before a Primary Care Practice had been set up. All children
      were investigated through home visits, checking of the immunization chart and
      relying on mothers' information. In 1986, a baseline study had identified an
      immunization coverage of under 60% for each of the scheduled vaccines. The
      current study confirmed that coverage was of 87% for three doses of DTP, 89% for
      Sabin, 88% for one dose of measles vaccine and 79% for BCG. Despite the high
      coverage achieved for each specific vaccine, when the basic schedule for the
      first year was verified, it was observed that only 75% of the children had
      received the full scheme. Immunization coverage is uneven in different census
      tracts, being higher in the poorest and more remote areas, where seam the health
      was given extra attention. A comparison with the routine administrative
      evaluation of the immunization coverage showed that this underestimated the real
      coverage. Maternal immunization uptake was also evaluated (antitetanus vaccine
      during pregnancy) and only 49% of the women were found to be adequately
      protected. The information collected led to a reorganization of the whole
      immunization program in a 100% coverage.

PMID- 8539533
TI  - [Medical education and the integration of teaching and health care activities].
AB  - A research project involving eighty first-year medical students who observed the
      experiences of first-time patients admitted to a university hospital in South
      eastern Brazil was undertaken during the first semester of 1989. The students
      conducted 260 interviews and followed the patients through from the time of
      admittance, observing the patients' expectations, values and attitudes towards
      minor complaints. The objective of the experience was to open a forum for
      discussion about excessive specialization and inadequacies in the curriculum in
      preparing the future medical professional to meet the needs of the population.
      Both the criticisms in the students' testimonies and the data collected at the
      interviews, as well as the concrete facts and practical proposals regarding the
      modification of the curriculum, concur with the Edinburgh Declaration of 1988.
      They point to the need for the adoption of a mode by which teaching and
      assistance activities, might be integrated from the very beginning of the
      physician's training.

PMID- 8539534
TI  - [Knowledge and use of alternative medicine among elementary school students and
      teachers].
AB  - The knowledge and use of popular cures was investigated as part of health
      education project in such a way as to develop and expand the existing
      possibilities for critical and constructive discussion in the school within the
      health program. It was hoped that this would result in the retrieval and in an
      increase in the value attributed to information concerning this nonsystematized
      knowledge present in a controversial and poorly accepted form in the practices of
      the population. One hundred and five teachers and 162 students of the 1st to 4th
      grades of the four primary schools on the outskirts of Belo Horizonte were
      interviewed. One hundred and five of the teachers answered the questions put.
      Twenty-three (32.4%) of the teachers said they believed in special cures, 69
      (65.7%) thought that certain diseases could be treated with homemade remedies for
      these, 54 (78.3%) were able to associate a particular disease with a particular
      medicinal plant and 15 (21.7%) prescribed a treatment without any association
      with a particular disease, 36 (34.3%) cited a disease without relating this to a
      particular herb. One hundred and one (62.3%) of the students believed that
      homemade remedies are effective for certain diseases. Amongst the teachers and
      students various diseases were mentioned as well as different symptoms and organs
      that can be cured by medicinal plants, roots or traditional healers. A little
      more than 50% of the two groups of students (1st and 2nd grade, 3rd and 4th
      grade) live in families who make use of traditional healers to provide
      alternative cures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539535
TI  - [Hexachlorocyclohexane contamination in urban areas of the south eastern region
      of Brazil].
AB  - A factory for producing the pesticide hexachlorocyclohexane (HCR) in its
      technical grade (mix of the alpha, beta, gamma, and delta isomers), that belonged
      to the former Institute of Malaria Sciences, then Ministry of Education and
      Health, located in the "Cidade dos Meninos", county of Duque de Caxias, State of
      Rio de Janeiro, was closed down in 1955. Part of its production and wastes - many
      tons this mix - were left behind on the site. The action of winds and rain as
      well as the movement of the local inhabitants - approximately 1,000 people,
      including 400 children, have caused the scaltering of this agent. Blood specimens
      from the inhabitants showed a high human contamination levels, with the highest
      concentration (beta isomers) being found in people living within a 100 meter
      radius of the ruin of the factory. Local soil and pasture samples taken at
      distances of less than 100 m from the ruin of the former factory showed HCH
      isomer concentrations of the order of thousands of ppb, thus providing evidence
      of high environmental contamination.

PMID- 8539536
TI  - [Alternatives for the financing of health care in Latin America and the
      Caribbean].
AB  - Latin America and the Caribbean (LAC) countries are experiencing both an economic
      crisis and a crisis in the public sector. As a result it is impossible to
      increase the amount of resources available to the health sector, unless there is
      a drastic restructuring of the way in which financing occurs. The measures so far
      referred to in the economic debate - user fees, cost recovery, privatization - at
      best represent partial solutions. Given the magnitude of health problem in LAC
      countries, they are unable to generate the amount of money needed to cover the
      deficit of financial resources for medical treatment. The central idea behind
      this article is that in order to cover the deficit of resources for medical it is
      necessary to utilize fiscal resources. It is shown that it is possible to
      increase the amount of financial resources available for medical treatment either
      through increases in taxes and/or through an increase in the proportion of the
      government budget dedicated to medical treatment. Increases in taxes collected
      provide a feasible alternative. In some of the poor countries of Latin America
      and the Caribbean, the proportion of the Gross National Product that goes for the
      payment of taxes is well below the figure for that proportion found in developed
      countries. To increase the proportion of the government budget dedicated to
      medical treatment is a political decision that depends solely upon the discretion
      of the governments concerned. The potential of Social Emergency Funds and debt
      swaps to finance innovations in the production of medical treatment services,
      thus maintaining the current level to activity in the sector, is discussed.

PMID- 8539537
TI  - [Inequities in health policies: the Latin American case].
AB  - Four points relating to the iniquities of the health services are brought out. In
      the first, the economic crisis the region has been going through during recent
      decades, is discussed and the contention that the tendency to an overall
      improvement of the living conditions has not been deeply affected by this crisis
      is questioned. In the second the characteristics of the Latin-American process of
      development, marked by the deepening of the iniquities is examined. In the third
      an analysis of the pattern of social protection in the region is presented and in
      the last two polar models for the reformation of this pattern are discussed.

PMID- 8539538
TI  - [The first cholera outbreaks in Mozambique].

PMID- 8539540
TI  - Decline of herpes simplex virus type 2 and Chlamydia trachomatis infections from
      1970 to 1993 indicated by a similar change in antibody pattern.
AB  - Antibodies to herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis (Ct)
      were determined in sera from pregnant women from 1970 and at intervals up to
      1993. The trends for HSV-2 and Ct infections were deduced from the observed
      antibody rates in different age groups during the observation period. Total
      antibody rates for HSV-2 tended to decline toward the end of the period when age
      matched groups were compared, while the Ct antibody rates peaked in 1979 and then
      declined gradually. Age-specific antibody rates showed declining frequencies in
      women younger than 20 years for both HSV-2 and Ct over the study period. Women 35
      years of age and older in the early 1990s had significantly higher antibody rates
      than younger women at that time or than women of similar age in the early 1970s.
      This group of slightly older women with high antibody rates in the 1990s were 15
      20 years of age in 1970 when a high antibody frequency was noted in this age
      group. High antibody rates against both HSV-2 and Ct in older pregnant women in
      the early 1990s may thus reflect a high incidence of these infections around
      1970. The declining rates of antibodies in the youngest women would suggest a
      declining incidence of primary infections in this group.

PMID- 8539539
TI  - Antibodies against hepatitis viruses in merchant seamen.
AB  - Seamen constitute a special group of international travellers who may run an
      increased risk of contracting hepatitis, because of visits to foreign ports and
      the particular environment on board ship. The purpose of the survey was to assess
      the prevalence of serological markers for hepatitis A, B and C virus infection
      among seamen and to identify present and previous risk factors for infection. 515
      seamen were studied. The prevalence of antibodies against hepatitis A was 0.3% in
      subjects below 40 years of age, increasing with age above 40 years, and highest
      among those who had sailed in international trade. The prevalence of antibodies
      against hepatitis B was 2.7% in subjects below 40 years of age, increasing to
      35.7% in the group above 60 years of age. Hepatitis C antibodies occurred in
      1.2%. Vaccination of sailors against hepatitis A should follow the same
      recommendations as to other travellers. The prevalence of hepatitis B was higher
      than in reference groups of non-seamen but, because hepatitis B is only one of
      many blood-borne diseases, prevention should be directed towards changes in
      behaviour rather than vaccination, except for special groups. Young seamen in
      international trade were found to be most at risk of contracting sexually
      transmitted diseases.

PMID- 8539541
TI  - Severe community-acquired pneumococcal pneumonia. The French Study Group of
      Community-Acquired Pneumonia in ICU.
AB  - Streptococcus pneumoniae is the most frequent pathogen of severe community
      acquired pneumonia (CAP) necessitating hospitalization. The main objective of
      this multicentre prospective study was to determine the value of clinical,
      biological, and radiological features for predicting pneumococcal etiology and to
      define prognostic factors. Streptococcus pneumoniae was isolated in 43/132
      patients (33%) with CAP requiring ICU treatment. The mean age of the patients
      with pneumococcal pneumonia was 55 +/- 17 (SD) yrs and 34 were male. On
      admission, 14 patients with pneumococcal pneumonia were in shock, 24 were
      mentally confused, and 27 required mechanical ventilation during their
      hospitalization. Among the clinical, biological, and radiological features, fever
      > 39 degrees C, pleuritic chest pain, lobar distribution or alveolar
      consolidation, and an increase in immature granulocytes > or = 5% of WBC were
      more frequent in pneumococcal pneumonia than in other etiologies. Mortality was
      35%. Fatal outcome was significantly related to the presence of impaired
      alertness, septic shock, mechanical ventilation, acute renal failure, and
      bacteremic pneumonia.

PMID- 8539542
TI  - Role of aeromonas isolated from feces of Finnish patients.
AB  - Aeromonas species were isolated from 249/13,027 (1.9%) stool samples submitted to
      the Dept. of Bacteriology and Immunology, University of Helsinki, during 1 year,
      to be cultured for bacterial enteropathogens. Aeromonas was the third most common
      enteropathogen isolated, after campylobacter (3.6%) and salmonella (3.3%).
      Isolates and clinical information from 234 Aeromonas patients were available for
      further study. A. caviae (41%), A. hydrophila (27%), and A. veronii biovar sobria
      (22%) were the most frequent isolates. In 15% of the patients, other
      enteropathogens were found along with aeromonas. Only 2% of all aeromonas
      positive patients were found to be asymptomatic, whereas no aeromonas isolates
      were detected in the stools of 343 asymptomatic individuals. Almost all (96%)
      patients with aeromonas in their feces had gastroenteritis. Patients infected
      with A. veronii biovar sobria had a shorter illness course and had more often
      travelled abroad. In conclusion, Aeromonas spp. were found to be a potential
      cause of diarrhea in Finnish patients.

PMID- 8539543
TI  - Association of Bacteroides fragilis with childhood diarrhea.
AB  - Enterotoxigenic strains of Bacteriodes fragilis (ETBF) have recently been found
      to be associated with diarrheal illness in Apache and Bangladeshi children. This
      study was conducted to define the role of ETBF in diarrhea of children in an
      urban setting. Fecal specimens from 991 children with diarrhea and 581
      asymptomatic age-matched controls were cultured for B. fragilis (BF). The
      isolates were tested for enterotoxin production using a human colonic epithelial
      cell line. BF was isolated from 318 (32.1%) of the patients and 123 (21.2%) of
      the controls (p < 0.001). In children < 1 year old which comprised about 50% of
      both patients and controls, the BF isolation rates were comparable (26.5% vs
      25.7%; p = 0.812), contrasting with the significant difference in isolation rates
      for children > or = 1 year (37.6% vs 16.5%; p = < 0.001). Overall, ETBF were
      identified in 4.4% of patients and 3.1% of controls (p = 0.2). However, ETBF were
      significantly associated with diarrheal disease in children 1-5 years (5.4% vs
      1.8%; p = 0.033) and 1-10 years (4.8% vs 1.5%; p = 0.021) in age. ETBF were
      isolated the year round and comprised 14.4% and 15% of the BF isolated from the
      patients and controls, respectively, suggesting that part of the indigenous BF
      are inherently enterotoxin producers. In this study, BF and ETBF were associated
      with diarrheal illness in children 1-10 years old.

PMID- 8539544
TI  - Randomized study of sulfamethoxazole-trimethoprim versus aerosolized pentamidine
      for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with
      AIDS.
AB  - In a prospective, randomized open-label trial, the efficacy of sulfamethoxazole
      trimethoprim (SMX-TMP) 400/80 mg b.i.d. was compared with the efficacy of
      aerosolized pentamidine (AP) 60 mg every 2nd week as secondary prophylaxis (SP)
      against recurrence of Pneumocystis carinii pneumonia (PCP) in AIDS patients. 94
      patients participated in the study, 47 in each group. The patients were observed
      for a mean period of 17.2 months. PCP recurred in the AP group in 8 cases, while
      1 relapse occurred in the SMX-TMP group. The one-year cumulative relapse rate was
      9.0% (95% CI 0-19%) in the AP group compared with 2.4% (95% CI 0-8%) in the SMX
      TMP group (p < 0.05). The odds ratio was 4.2 (95% CI 0.5-39.8) in favour of SMX
      TMP. Furthermore, we found a tendency towards a protective effect against
      toxoplasmosis in the SMX-TMP group, though there was no difference in survival
      between the two groups. There was no statistical difference in frequency of
      crossover from one therapy form to the other. Based on these data we recommend
      SMX-TMP for secondary PCP prophylaxis.

PMID- 8539545
TI  - Is penicillin the appropriate treatment for recurrent tonsillopharyngitis?
      Results from a comparative randomized blind study of cefuroxime axetil and
      phenoxymethylpenicillin in children. The Swedish Study Group.
AB  - The efficacy of cefuroxime axetil compared with phenoxymethylpenicillin (PcV) was
      studied in group A beta-haemolytic streptococci (GAS) culture-proven tonsillitis
      in children aged 3-12 years with a history of at least 1 episode of
      tonsillopharyngitis requiring antibiotic therapy during the previous 3 months.
      This was a comparative, randomized, investigator-blind, multicentre study. A
      total of 236 children received either cefuroxime axetil suspension or PcV syrup.
      Inclusion criteria were a positive, rapid, group A strep test verified by
      bacteriological culture and clinical signs and symptoms of tonsillopharyngitis.
      Cefuroxime axetil treatment gave a significantly higher bacteriological
      eradication rate and clinical cure rate than PcV. At day 2-5 post treatment the
      eradication rates were 99/114 (87%) for cefuroxime axetil vs 61/109 (56%) for PcV
      (p < 0.001). The clinical cure rates were 98/114 (86%) and 73/109 (67%)
      respectively (p < 0.01). Up to 21-28 days post-treatment, 9/114 (8%) cefuroxime
      axetil patients and 37/109 (34%) PcV patients were treatment failures or had
      recurrence/reinfection of GAS tonsillopharyngitis (p < 0.001). More than 90% of
      the patients who experienced bacteriological treatment failure at either the
      first or second follow-up had the same serotype isolated pre- and post-treatment.
      During the study period, 21/114 (18%) patients in the cefuroxime axetil group and
      50/109 (46%) patients in the PcV group received additional antibiotics (p <
      0.001). No serious adverse events were noted and the mild adverse events were
      equally distributed among the patients in the 2 study groups: 15% for cefuroxime
      axetil and 14% for PcV.

PMID- 8539546
TI  - Treatment of acute maxillary sinusitis--comparing cefpodoxime proxetil with
      amoxicillin.
AB  - In order to evaluate the clinical efficacy and tolerance of cefpodoxime proxetil,
      compared with that of amoxicillin in the treatment of acute bacterial maxillary
      sinusitis, a randomized, double-blind, parallel group comparative study was
      performed. A total of 286 adults patients were included at 12 centres, each
      treatment group consisting of 143 patients. Each patient was treated for 10 days
      and observed before and after treatment. The observations included clinical,
      roentgenological, bacteriological and laboratory examinations. At inclusion, the
      most common pathogens were Haemophilus influenzae (24%) and Streptococcus
      pneumoniae (17%). In the per protocol analysis, 117 patients in the cefpodoxime
      group and 113 in the amoxicillin group were evaluable for clinical efficacy. The
      clinical response rates were 96% and 91%, respectively. The corresponding figures
      in the intent-to-treat analysis were 130 and 128 patients, with clinical response
      rates of 93% and 88%, respectively. Cefpodoxime proxetil proved clinically as
      effective as amoxicillin in the treatment of acute bacterial maxillary sinusitis.
      It was more effective in eradicating H. influenzae and was more efficient in
      improving the radiological score. Adverse events were reported in 20% of
      cefpodoxime cases and in 16% of amoxicillin cases. There was no statistically
      significant difference between the groups.

PMID- 8539547
TI  - Fluconazole for primary prophylaxis of AIDS-associated cryptococcosis: a case
      control study.
AB  - In order to verify whether fluconazole has a prophylactive effect against the
      occurrence of cryptococcosis in HIV-infected patients and to identify other
      factors capable of increasing or reducing the risk of this infection, we arranged
      a case-control study of 17 patients with cryptococcal infection. 34 controls were
      selected, matched by presence of an AIDS-defining event, CD4 cell count, and date
      of T-cell phenotyping. No significant difference in exposure to fluconazole, in
      total days of treatment, or in total dose administered was observed between cases
      and controls. However, control patients took a significantly higher average daily
      dosage of fluconazole and a linear tendency in risk reduction (p = 0.04) in
      relation to increasing dosage was observed. Antiretroviral therapy and an average
      daily fluconazole dose exceeding 150 mg both each reduced the risk of a
      cryptococcal infection.

PMID- 8539548
TI  - Intravenous immunoglobulin treatment in children with Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome is an acquired demyelinating polyneuropathy that is
      presumed to be immune-mediated. On the basis of this assumption, intravenous
      immunoglobulin (IVIG) has been used in the treatment of Guillain-Barre syndrome
      in recent years and found to be effective. To test this we performed a randomized
      study in patients with Guillain-Barre syndrome by giving IVIG (1 g/kg body weight
      per day over 2 consecutive days) in 9 children who were compared with 9 patients
      who were observed but not given specific therapy. We concluded that intravenous
      immunoglobulin is a safe and effective treatment for childhood Guillain-Barre
      syndrome which shortens the time to recovery.

PMID- 8539549
TI  - Bacteremia at a Danish university hospital during a twenty-five-year period (1968
      1992).
AB  - In the 25-year period 1968-92, 3,317 out of 477,420 patients admitted to
      Frederiksberg Hospital experienced 3,491 episodes of bacteremia.
      Enterobacteriaceae dominated as causative agents (57%), following by Gram
      positive cocci (31%) and anaerobes (7%). Polymicrobial bacteremia was found in 8%
      of the episodes. The incidence of Enterobacteriaceae bacteremia culminated in the
      middle (1978-82) of the period (4.7/1,000 admissions) and decreased during the
      last decade. Gram-positive bacteremia increased throughout the period (from 1.8
      to 2.9; p < 0.001), due mainly to increasing incidences of bacteremia caused by
      non-hemolytic streptococci, Streptococcus pneumoniae and coagulase-negative
      staphylococci. Bacteroides fragilis accounted for a rising incidence of anaerobic
      bacteremia (from 0.3 to 0.7; p < 0.05). Clinical data were available for the
      2,599 bacteremic episodes in the 20-year period 1968-87. 59% of these were
      hospital acquired. Of those, 38% were associated with indwelling catheters,
      mainly bladder catheters (28%) and i.v. lines (7%). The urinary tract dominated
      as source of bacteremia (46%), followed by the respiratory (11%) and the
      gastrointestinal tract (9%). Half of the patients had predisposing underlying
      diseases, most frequently malignancies (20%) and diabetes mellitus (7%). The
      mortality rate related to bacteremia decreased from 25% to 11% (p < 0.001). More
      than half (55%) of the fatal cases related to bacteremia occurred within the
      first 2 days after the first positive blood culture was obtained. Logistic
      regression analysis defined 7 variables that independently influenced the outcome
      related to bacteremia: age, source, culture verification of source, shock, body
      temperature, leukocyte count and empiric antibiotic treatment.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8539550
TI  - Bacteraemia due to Escherichia coli in a Danish university hospital, 1986-1990.
AB  - 433 episodes of E. coli bactereaemia over a 5-year period in a Danish university
      hospital were studied with special emphasis on possible differences between
      nosocomial (NO) and community-acquired (CA) cases. Data from 186 males and 247
      females with ages ranging from 9 days to 94 years were recorded. The average
      incidence of E. coli bacteraemia was 24.4 episodes/10,000 admissions/year. Older
      females accounted for the largest number of cases, which reflected the
      composition of the background population. The highest risk of infection was in
      males 80-89 years of age. The highest frequency of NO infections was in the
      departments of Intensive Care (90%) Orthopaedic Surgery (87%) and Haematology
      (80%). The most common focus was the urinary tract, with 72% of the episodes with
      a known focus, while the biliary tract was the focus in 14%. NO bacteraemia was
      independently related to immunosuppressive therapy, presence of predisposing
      factors, polymicrobial bacteraemia and presence of a non-urinary tract focus. A
      urinary tract focus was associated with CA bacteraemia, monomicrobial infection,
      female sex and a normal or elevated total white blood cell count. Patients with
      NO bacteraemia had predisposing factors more often than had CA patients,
      especially haematological malignancies and immunosuppressive therapy. Lack of a
      known bacterial focus was more common in NO than CA episodes, particularly among
      patients with haematologic malignancies. The overall mortality was 21%. Increased
      mortality was independently related to leukopenia (45%), immunosuppressive
      therapy and NO bacteraemia.

PMID- 8539551
TI  - Detection by enzyme immunosorbent assay of Toxoplasma gondii IgG antibodies in
      dried blood spots on PKU-filter paper from newborns.
AB  - Different ways of eluting IgG antibodies against Toxoplasma gondii from blood
      spots on PKU filter papers from newborns were examined, and the eluate was
      analysed by Enzyme Immunosorbent Assay (EIA). 10-mm diameter discs (method A),
      and 3-mm discs (method B) were eluted overnight, and 3-mm discs were eluted
      directly for 2 hours in the EIA wells (method C). Two groups of paired samples
      were tested: blood spots on the PKU card from the newborn, cord blood, and a
      venous blood sample from the mother collected shortly after delivery (Group 1,
      191 samples); or PKU cards from the newborns and serum collected from the mother
      during the first trimester (Group 2, 426 samples). The best results were found
      for Group 1; method A, a sensitivity of 100% (63/63), and a specificity of 100%
      (128/128) (r = 0.934, P < 0.0001), and for Group 2; method C, a sensitivity of
      100% (125/125), and a specificity of 100% (301/301) (r = 0.822, P < 0.0001). When
      method C, was used on 188 samples stored for 16-18 month at -20 degrees C, a
      sensitivity of 100% (62/62) and a specificity of 99.2% (125/126) (r = 0.913, P <
      0.0001) were found. The PKU filter paper method is reliable and reproducible, and
      can be used in screening projects based on analysis of neonatal samples, and in
      epidemiological studies on toxoplasmosis in pregnant women.

PMID- 8539552
TI  - Cost-benefit analysis of screening for toxoplasmosis during pregnancy.
AB  - Congenital toxoplasmosis is a risk for fetus both in 'low' and 'high risk' areas.
      A cost-benefit analysis based on data from a Finnish prospective study (20.3%
      seropositivity of pregnant mothers and incidence of 2.4/1,000 seronegative
      pregnancies) and on Finnish cost data was performed to compare the no-screening
      and screening alternatives for primary toxoplasma infections during pregnancy. A
      maternal-feto transmission risk of 40%, effectiveness of treatment of 50%, and
      discount rate of 4% were used as other baseline probabilities. The calculations
      were carried out by decision analysis combined with sensitivity analysis. The
      total annual costs of congenital toxoplasmosis without screening amount to US$
      128/pregnancy/year, and with systematic serological screening, US$ 95/pregnancy.
      Thus screening reduces the costs by 25%. The present value of net savings in
      Finland would be US$ 2.1 million every year. A one-way sensitivity analysis
      showed that screening together with health education is preferable to health
      education without screening if the incidence of maternal primary infections
      exceeds 1.1/1,000 and effectiveness of treatment is better than 22.1%. Screening
      for toxoplasma infections during pregnancy is economically worthwhile even in a
      country with a low incidence. A scheme of systematic screening for maternal
      primary toxoplasma infections combined with health education should be
      considered.

PMID- 8539553
TI  - Response and decline of serum IgG antibodies to pertussis toxin, filamentous
      hemagglutinin and pertactin in children with pertussis.
AB  - The serum IgG antibody response and decrease to 3 Bordetella pertussis antigens
      was compared in children with pertussis. Sera were obtained at the first clinical
      visit and 1, 3 and 12 months later from 89 children with > or = 3 weeks of
      paroxysmal cough. IgG antibodies to pertussis toxin (PT), to filamentous
      hemagglutinin (FHA) and to pertactin were determined with ELISA. Of 54 children
      with culture-confirmed pertussis or culture-confirmed familial exposure, 45 (83%)
      had a significant (> or = 3 fold) increase in PT IgG and 40 (74%) in FHA IgG
      antibodies, while only 29 (54%) had a significant increase in pertactin IgG
      antibodies. Significant decreases in PT, FHA and pertactin IgG antibodies were
      found in 34 (63%), 9 (17%) and 28 (52%) children, respectively. In the remaining
      35 who did not have culture-confirmed disease, significant PT and/or FHA IgG
      antibody increases (criteria for pertussis according to the WHO definition) were
      found in 17 (49%). Only 6 of these 17 children had a significant pertactin IgG
      antibody increase. Of the remaining 18 children (who did not fulfil WHO criteria
      for pertussis), significant decreases in PT and/or FHA IgG antibodies were found
      in 13. We conclude that a serum IgG reaction to PT and FHA occurs in almost all
      children with pertussis. An increase in pertactin IgG antibodies occurs less
      frequently than against PT and FHA. Significant decreases in PT or FHA IgG
      antibodies in children with clinical pertussis might be of use as a diagnostic
      criterion in children brought late for examination.

PMID- 8539555
TI  - Actinobacillus actinomycetemcomitans pneumonia with chest wall and subphrenic
      abscess.
AB  - A 14-year-old girl had progressive dyspnea and right lower chest pain for about 1
      1/2 months and a weight loss of 3 kg in 2 months. Chest X-ray revealed right
      pleural effusion and a round infiltration over the right lower chest, initially
      suspected to be malignant. Image study revealed consolidation in the right middle
      and lower lobes with abscess-like lesions around the right lower pleura and
      transdiaphrenic involvement to the subphrenic region. The lesion had also invaded
      the intercostal muscle. The pleural abscess was obtained by fiberoptic
      thoracoscopy, and culture of the pus grew typical colonies of Actinobacillus
      actinomycetemcomitans. After the causative microorganism had been identified,
      cefoxitin was given for 2 weeks followed by oral amoxicillin (250 mg/6 h) for a
      total period of 3 months. Follow-up chest X-ray revealed resolution of the lung
      lesions and the patient recovered gradually without any sequelae.

PMID- 8539556
TI  - Haemophilus aphrophilus discitis and vertebral osteomyelitis.
AB  - An unusual case of discitis and vertebral osteomyelitis due to Haemophilus
      aphrophilus is described. Infections due to this organism have usually responded
      to treatment with beta-lactam antibiotics. However, our isolate was resistant to
      third-generation cephalosporins which has not been reported previously in the
      world literature. The patient made a good clinical response to ciprofloxacin
      treatment.

PMID- 8539554
TI  - Safety and immunogenicity of two acellular pertussis vaccines with different
      pertussis toxoid and filamentous hemagglutinin content in infants 2-6 months old.
AB  - The optimal composition and antigen content of acellular pertussis vaccines is
      not known. Two vaccines with different quantities of pertussis toxoid (10 and 20
      micrograms) and filamentous hemagglutinin (5 and 20 micrograms) and identical 69
      kD protein (3 micrograms) and fimbriae 2 and 3 (5 micrograms) combined with
      diphtheria and tetanus toxoids were compared in a randomized, double-blind study
      in 2,050 infants undergoing their primary immunization series at 8 centers in the
      US and Canada. A 6:1 increased antigen to lower antigen allocation was used; 96%
      of infants received 3 doses and completed the study. A 'clinically significant'
      local reaction was reported in 3-6% of participants after each dose. Erythema was
      the most common reaction occurring in 3-5% of infants after the second or third
      dose. A clinically significant systemic adverse reaction was reported in 28-34%
      of vaccinees (or vaccinated children) after each dose; fever (7-18%) and
      fussiness (12-17%) were most common. There were no differences in adverse events
      between the 2 vaccine formulations. Antibody responses were measured in 292
      infants at 1 center. At 7 months, geometric mean anti-filamentous hemagglutinin
      antibody titers were higher in recipients of the higher antigen content vaccine
      (p < 0.001) whereas recipients of the lower antigen content formulation had
      higher anti-fimbriae antibody (p < 0.001) and agglutinin titers (p < 0.05). No
      differences were detected in anti-pertussis toxin or other antibody responses
      between the formulations. We conclude that increasing the antigen content of the
      acellular pertussis vaccine had a variable effect on antibody response but was
      not associated with increased adverse reactions.

PMID- 8539557
TI  - Aeromonas hydrophila lung abscess in a previously healthy man.
AB  - We present a case of multilocular lung abscess caused by Aeromonas hydrophila,
      found in both sputum and bronchial washing. No aspiration or other significantly
      contributory medical conditions were found. We believe this to be the first
      report of lung abscess caused by this organism in a previously healthy
      individual.

PMID- 8539558
TI  - An unusual gastrointestinal presentation of leishmaniasis.
AB  - While visceral leishmaniasis (VL) generally occurs in immunocompetent subjects in
      endemic areas, it has been increasingly recognised as an important opportunistic
      infection in the immunocompromised including those infected with the human
      immunodeficiency virus. We report an unusual presentation of visceral
      leishmaniasis in a patient with the acquired immunodeficiency syndrome (AIDS)
      with disease which appeared to be limited to the gastrointestinal tract.

PMID- 8539559
TI  - Hepatitis B in parts of former USSR.
AB  - Hepatitis B is more frequent in many countries in eastern Europe than in the
      western part. In Poland the incidence is as high as 34 notified cases per 100,000
      inhabitants. In the Baltic states the incidence is between 10 and 20, and in
      Russia 23 cases per 100,000 inhabitants. In the Baltic states the incidence has
      declined since 1986. This reduction has been most prominent in Lithuania, with
      69%, followed by Latvia with 43% and Estonia with 23%. The infection is very
      often (> 50%) spread by non-sterile medical instruments.

PMID- 8539560
TI  - Reorganisation of primary afferent nerve terminals in the brainstem after
      peripheral nerve injury. An anatomical study in cats.
AB  - A pure sensory nerve (the superficial branch of the radial nerve) in adult cats
      was cut to investigate the changes in the nerve endings (terminals) on the
      neurons of the nucleus cuneatus of the brainstem. In one group of cats (n = 22)
      the ends of the cut nerve were approximated immediately by epineural suturing to
      promote optimum regeneration. In another group (n = 11) the proximals tump of the
      nerve was enclosed in a capsule to prevent regeneration. Four to 17 months later
      the same nerve was re-exposed. The sutured nerves were cut and nerve-tracer was
      exhibited to the proximal end of the cut nerves and to the proximal stump of the
      nerves which had been encapsulated. The purpose was to investigate the labelling
      of nerve terminals in the cuneate nucleus, because it receives an input of
      primary afferents from the front leg. The nerve and the cuneate nucleus of the
      opposite side served as controls. Labelled terminals were distributed throughout
      the dorsal part of the entire rostrocaudal extent of the cuneate nucleus. The
      distribution was patchy and was superimposed on clusters of nerve cells. The
      quantity of labelled nerve terminals on the experimental and control sides was
      compared: 60% of the labelling observed on the control side was in the sutured
      nerves while the encapsulated nerves exhibited only 32%. This difference was
      apparent 4 months after transection of the nerve. Up to 17 months after the nerve
      was cut, however, there was some increase in the quantity of labelled nerve
      terminals and this was most apparent in cats in which the nerves had been
      sutured.

PMID- 8539561
TI  - Fibrin sealant matrix supports outgrowth of peripheral sensory axons.
AB  - It has been suggested that fibrin-based matrix has an important role during the
      early stage of nerve regeneration. A fibrin sealant matrix, which was made by
      combining diluted human fibrinogen and thrombin, was used as a substrate for in
      vitro elongation of neurites and in vivo regeneration of axons. In the in vitro
      experiment, dissociated embryonic chick sensory neurons were cultured on dishes
      coated with fibrin sealant matrix and compared with the solution of
      thrombin/calcium chloride, or with poly-D-lysine (PDLctr). After 16 hours,
      cultures were stained immunohistochemically with a monoclonal antineurofilament
      antibody. The neurons survived well, and an abundant network of neurites,
      qualitatively similar to that on PDLctr, developed on the fibrin sealant matrix.
      The percentage of neurons that had outsprout at 16 hours was the same both in the
      fibrin sealant matrix and PDLctr groups. By contrast, all the neurons plated on
      the dishes treated with the solution of thrombin/calcium chloride were dead after
      16 hours. Immunohistochemical staining of fibrinogen also showed an even
      distribution of fibrin matrix over the culture dishes. For the in vivo
      experiments, 48 rat sciatic nerves were cut and reconnected with two epineurial
      stitches. Fibrin sealant matrix or phosphate buffer solution was applied to the
      transsected and repaired region. Pinch reflex test showed that the regeneration
      of the leading sensory fibre was significantly faster in the fibrin sealant
      matrix group than in the control group at 3 and 4 days. These results indicate
      that fibrin sealant matrix accelerates regeneration of axons in vivo during the
      early phase, and also supports elongation of neurites in vitro.

PMID- 8539562
TI  - Survival and development of reimplanted fetal epiphyses. An experimental study.
AB  - An experiment was undertaken to study the survival and development of fetal
      epiphyses after excision and reimplantation in rats. The proximal part of fibula
      in the hindlimb was dissected free from surrounding tissues and then reimplanted
      again. Of 80 fetuses that were operated on, nine that had been operated on
      survived to birth. Histological examination on the hindlimbs of these rats at
      four and six weeks after birth showed that the reimplanted segments survived, and
      the bony nuclei of the epiphyses were present. Radiographically, at 6 weeks old,
      secondary centres of ossification at proximal ends of the fibulas could be seen
      in both operated and normal limbs. These results indicate the clinical
      possibility of correcting congenital musculoskeletal abnormalities in the future
      by in utero transplantation of epiphyses.

PMID- 8539563
TI  - Evaluation of an allogeneic cultured dermal substitute composed of fibroblasts
      within a spongy collagen matrix as a wound dressing.
AB  - The purpose of this study was to examine whether epithelialisation is promoted
      when an allogeneic cultured dermal substitute is used as a biological wound
      dressing. The dermal substitute was prepared by plating fibroblasts on to a
      spongy collagen matrix, and then culturing them for 7 to 10 days. A new animal
      wound model was designed to measure re-epithelialisation quantitatively. A full
      thickness skin defect was made on the dorsum of each of 33 rats; the skin was
      excised, leaving a layer of pannicular carnosus with an island of intact skin in
      the central portion of the skin defect. In the first group of rats (n = 13), a
      piece of cultured dermal substitute was applied to the wound, and a medicated
      covering material was placed over it. Re-epithelialisation from the island of
      intact skin was monitored over a period of 7 days. In the second group of rats (n
      = 10), the wound was covered with an acellular collagen matrix in conjunction
      with the medicated covering material, and in the third group of rats (n = 10),
      the wound was covered with the medicated covering material alone. Both the
      macroscopic and histological findings indicated that the epithelial migration of
      the first group of rats was far more rapid than that in the other two groups. It
      comes to the conclusion that the application of this new fibroblastic cultured
      dermal substitute provided a good environment for the promotion of wound healing.

PMID- 8539564
TI  - The "bottle brush": a new concept for uncemented anchorage of bone implants.
      Preliminary mechanical and biomechanical studies.
AB  - We present a new concept for bone of implants, the "bottle brush". It may be
      suitable for joint prostheses, dental or percutaneous implants, or other devices
      fixed into bone. Mechanical pullout studies in artificial brass cavities of
      different sizes and shapes and implantation studies in 20 rabbits, have been
      successfully carried out. Further experimental and clinical studies are in
      progress.

PMID- 8539565
TI  - Casting the implant for reconstruction of pectus excavatum.
AB  - Fourteen patients with pectus excavatum underwent a total of 17 operations for
      the insertion of subcutaneous implants aimed at camouflaging their defects. A
      silicone prosthesis in one patient early in the series caused severe capsular
      formation. Although a block of Proplast may occasionally be used with success,
      the rational solution to the problem is to produce a custom made Silastic implant
      that adheres optimally to the defect in each individual case. This retrospective
      study shows that a subcutaneous implant clearly improves the appearance of the
      chest wall in most of the patients.

PMID- 8539566
TI  - Long term results of skin expansion.
AB  - A series of thirty patients who underwent skin expansion have been followed up
      for at least three years. The residual scars were analysed with respect to site
      and disturbed sensitivity in expanded skin. In the head and neck region, the mean
      width of definitive scars was 3.5 mm for lesions that had originally measured a
      mean of 40 mm. On the trunk the postoperative width was 14 mm for lesions that
      had originally measured a mean of 82 mm. In the limbs, the corresponding lesions
      were 11 mm and 80 mm. The best cosmetic results were obtained on the forehead and
      limbs, taking into account the original lesions. There was objective disturbance
      on sensitivity (hypoaesthesiae) whatever the site of the lesion.

PMID- 8539567
TI  - Temporal artery island flap in reconstruction of the eyelid.
AB  - The temporal artery island flap, based on the anterior branch of the superficial
      temporal artery, was used in full thickness eyelid reconstructions of 11 patients
      (in four for both lids, in two for the upper lid and in five for extensive lower
      lid defects). The skin island was taken from the upper lateral frontal skin in
      front of the hairline to leave minimal scaring and create a long vascular
      pedicle. Mucosal or chondromucosal graft was used for the inner lining. In seven
      patients the arterial pedicle surrounded by a 0.5 cm wide band of subcutaneous
      tissue containing the corresponding veins, was tunnelled under the skin in a one
      stage procedure. In four cases, the pedicle was temporarily left above the skin
      to shorten the operating time. The temporal artery island flap is a reliable way
      of reconstructing both lids, or the lower lid in cases where the local flaps have
      been used in earlier operations. Because of the risk of bulging and for
      functional reasons, we do not recommend the flap for upper eyelid
      reconstructions.

PMID- 8539568
TI  - Effect of method of cleft palate repair on the quality of speech at the age of 6
      years.
AB  - Two methods of primary palatal repair were compared for the effect that they had
      on the speech of 6 year old children with cleft (lip and) palate. A Veau-Wardill
      Kilner V to Y pushback operation was done for 43 children (group V) and the
      Cronin modification for 60 children (group C) between the ages of 12 and 18
      months. The groups were compared with respect to the quality of speech assessed
      clinically by perception, by instrumental measures of nasalance, and by the
      number of velopharyngeal flaps required. The quality of speech was assessed in
      terms of perceived signs of velopharyngeal insufficiency: hypernasality, audible
      nasal air emissions, weakness of plosives and compensatory articulations.
      Hypernasality was significantly more common in group V (16/33, 48%) than in group
      C (11/49, 22%) (p = 0.01). The number of velopharyngeal flaps and the nasalance
      scores derived from most of the individual test sentences were similar in the two
      groups. The mean nasalance score for the whole set of test sentences was
      significantly higher in group V.

PMID- 8539569
TI  - Psychosocial adjustment in Norwegian adults who had undergone standardised
      treatment of complete cleft lip and palate. I. Education, employment and
      marriage.
AB  - Aspects of social and psychological adjustment were investigated in a sample of
      233 Norwegian adults 20-35 years old with repaired complete cleft of the lip and
      palate (CLP); in 126 the cleft was on the left, in 45 on the right, and in 62 it
      was bilateral. All subjects received a standardised regimen of care from the Oslo
      cleft palate team. The investigation, based on response to a questionnaire,
      partly replicated a national survey of social and economic life in the
      population, so that adults with complete clefts could be compared with a large
      control sample of the same age. This report covers education, employment, and
      marriage. The results confirm previous findings that there are few differences in
      educational attainment and employment between adults with CLP and other people.
      Fewer with CLP marry, and when they marry they do so later in life, particularly
      if the CLP is bilateral. Income seemed to be lower among married men and single
      women with CLP than among the control population.

PMID- 8539570
TI  - Penetration of flomoxef into human maxillary and mandibular bones.
AB  - Penetration of flomoxef into the maxillary and mandibular bones was assayed
      clinically to provide data about its usefulness for the prevention of
      postoperative infection after maxillofacial surgery. Twenty-one patients
      undergoing maxillofacial surgery at our department were given flomoxef 2 g
      dissolved in 20 ml of physiological saline intravenously over 3 minutes during
      operation, and the serum, maxillary and mandibular concentrations were measured
      1, 3, and 6 hours after injection by the band culture method using Escherichia
      coli 7437 as the indicator strain. The mean concentrations were 53.4, 16.1, and
      2.6 micrograms/ml, respectively, in the serum, 17.6, 7.8, and 1.0 micrograms/g in
      maxillary bone, and 16.4, 4.2, and 0.9 micrograms/g in mandibular bone. The mean
      bone:serum ratios at 1, 3, and 6 hours were 33.0%, 48.2%, and 36.8%,
      respectively, for maxillary bone, and 30.7%, 26.2%, and 35.7% for mandibular
      bone. When compared with previously reported data on the bone:serum ratios in jaw
      of various other intravenous antibiotics, our results show that penetration of
      flomoxef into maxillary and mandibular bone is extremely high. As all the
      intramaxillary and intramandibular concentrations exceed its MIC80 values against
      clinical isolates of bacteria frequently isolated in cases of infection in the
      oral and maxillofacial region, it is apparent that one intravenous shot of
      flomoxef 2 g allows penetration of the drug into the maxillary and mandibular
      bones at effective concentrations. Flomoxef is therefore potentially useful for
      the prevention and treatment of infections in the oral and maxillofacial region,
      as it has excellent penetration into the maxillary and mandibular bones.

PMID- 8539572
TI  - Subcapital fractures of the fourth and fifth metacarpals treated without
      splinting and reposition.
AB  - The aim of the study was to evaluate the results after treating subcapital
      fractures in the fourth and fifth metacarpals with immediate mobilisation and
      without splinting or reduction. We undertook a prospective clinical evaluation of
      36 subcapital fractures of the fourth and fifth metacarpals treated with
      immediate mobilisation and without splinting or reduction during the period 1
      January 1990 to 31 December 1992 in the accident and emergency department,
      Holstebro Central Hospital. After 4 weeks only 4 patients (11%) had restricted
      movement in the metacarpophalangeal joint (less than 0-80 degrees of movement).
      The fracture had healed in 33 patients (92%), and 31 of the patients (86%) were
      completely satisfied. We conclude that subcapital fractures in the fourth and
      fifth metacarpals can be treated without immobilisation or reposition.

PMID- 8539571
TI  - Fractures of the distal radius in a Norwegian city.
AB  - During a prospective one-year study (1988) all fractures of the distal radius in
      people over 20 years old were registered in Bergen, Norway. Six hundred patients
      with 609 fractures were treated. The incidence was 38/10000 population, and 79%
      of the fractures occurred in women. The age-specific incidence in women increased
      rapidly after the menopause and reached a maximum between 60 and 69 years. The
      incidence for women over 60 years of age is the highest reported. Among women
      over 50 years the incidence of fractures caused by minor falls varied depending
      on the season. The mean number of fractures was 3.6 times higher on days when
      there was snow on the ground compared with days when there was no snow. More than
      half the distal radial fractures occurred while out walking. Possible strategies
      to prevent fractures must include prevention of falls, in particular among
      postmenopausal women on winter days.

PMID- 8539573
TI  - Gait patterns after free flap reconstruction of the foot sole.
AB  - Walking patterns after reconstruction of soft tissue defects of the sole of the
      foot with free flap were studied in seven patients. Measurements included walking
      technique, ground reaction forces and electromyographic (EMG) activity during the
      gait cycle. The results showed that only one patient walked symmetrically; the
      remaining six had many differences between the legs, the asymmetry usually being
      noticed when the subjects walked barefoot. The most common change was the
      shortening of the stance phase of the injured foot. The maximal vertical ground
      reaction force decreased in the braking phase and in the push-off phase.
      Quantitative differences in EMG between the legs were less than expected. The
      present study gives some support to the hypothesis that altering the pattern of
      gait may contribute to soft tissue stability after resurfacing of the sole.

PMID- 8539574
TI  - [Diagnosis and treatment of hypertensive emergencies].
AB  - In hospital as well as in the office, the physician is often confronted with
      clinical situations in which blood pressure values are very high. In each case,
      he will have to evaluate rapidly the degree of emergency and the need for
      immediate antihypertensive therapy. In the last few years, the therapeutic
      approach to some hypertensive emergencies has changed. The purpose of the present
      article is to review: 1) the clinical situations where immediate control of blood
      pressure is necessary, 2) the present therapeutic approaches and 3) the cardiac
      and cerebral risks linked to an excessive and too rapid fall in blood pressure.

PMID- 8539575
TI  - [Sleep apnea syndrome, arterial hypertension and cardiovascular risks].
AB  - Excessive daytime somnolence is the main symptom of the obstructive sleep apnea
      syndrome (OSAS). Repetitive upper airway obstructions during sleep are followed
      by arousals and consequent sleep fragmentation. Furthermore, obstructive apneas
      or hypopneas and arousals are accompanied by fluctuations of blood pressure and
      heart rate. Several recent studies have found OSAS to be an independent risk
      factor for arterial hypertension and cardiovascular diseases.

PMID- 8539577
TI  - [Assessment and diagnosis of transient ischemic attacks].
AB  - Transient ischemic attacks (TIA) are defined as acute, retinal or focal-cerebral
      neurological symptoms, resulting from vascular disease, which resolve in less
      than 24 hours. Typical clinical signs are transient visual obscuration, sudden
      weakness of one arm or leg, loss of speech, and dizzy spells. These patients run
      a considerable risk of stroke; hence rapid diagnosis and treatment are mandatory.
      Differential diagnosis includes transient global cerebral function loss, non
      vascular transient focal attacks, as well as extracerebral causes of transient
      neurological symptoms. The following basic investigations are necessary for most
      patients with TIA: simple laboratory work-up, extra- and transcranial
      doppler/duplex-ultrasonography, cardiological examination and CT-scan.
      Angiography and MR-angiography are reserved for specific questions.

PMID- 8539576
TI  - [Hypertension and pregnancy. Diagnosis, physiopathology and treatment].
AB  - This review on hypertension in pregnancy focuses mainly on the pathophysiology
      and prevention of pregnancy induced hypertension which, when associated with
      proteinuria, is usually called preeclampsia. Rather than a genuine hypertensive
      disease, preeclampsia is mainly a systemic endothelial disease causing activation
      of platelets and diffuse ischemic disorders whose most obvious clinical
      manifestations involve the kidney (hence the proteinuria, edema and
      hyperuricemia), the liver (hence the hemolytic elevated liver enzymes and low
      platelets, or HELLP syndrome), and the brain (hence eclamptic convulsions).
      Hypertension is explained by increased vascular reactivity rather than by an
      imbalance between vasoconstrictive and vasodilating circulating hormones. This
      increased reactivity is due to endothelial dysfunction with imbalance between
      prostacyclin and thromboxane A2 and possibly dysfunction of NO and endothelin
      synthesis. The aggressive substances for endothelium are thought to be of
      placentar origin and the cause of their release is explained by placentar
      ischemia related to a defect of trophoblastic invasion of the spiral arteries.
      The etiology of this latter defect is unknown but involves immunologic mechanisms
      with genetic predisposition. The only effective treatment for PIH is extraction
      of the baby with the whole placenta. The decision for extraction is often a very
      delicate obstetric problem. Antihypertensive drugs are mainly indicated in severe
      hypertension (> 160-100 mm Hg), with the aim of preventing cerebral hemorrhage in
      the mother, but have not been shown to improve fetal morbidity or mortality.
      Eclamptic seizures can be prevented and treated more effectively with magnesium
      sulfate than with diazepam or phenytoin. Prevention of preeclampsia remains the
      main challenge. Whereas antihypertensive drugs are ineffective, calcium
      supplementation and low dose aspirin have proven effective but mainly in selected
      populations with a relatively high incidence of preeclampsia (> 8-10%). In
      multiparas the selection of such a high risk population is relatively easy when
      at least 2 (or 1?) previous pregnancies were complicated with early preeclampsia
      and/or intrauterine growth retardation. In nulliparas the selection of the high
      risk population is still a subject of research. The 2 most promising criteria are
      abnormal Doppler velocimetry of the uterine arteries at around 20 weeks of
      amenorrhea, and abnormally high plasma levels of beta HCG at 17 weeks of
      amenorrhea.

PMID- 8539578
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Modification of
      phosphate metabolism by administration of aluminum hydroxide. 1956].

PMID- 8539579
TI  - [Clinical research: where does it come from? Where is it going?].
AB  - In this editorial the author examines briefly the past, present and future of
      clinical investigation in general and particularly in Switzerland, where the same
      problems are encountered as in other European countries and North America. The
      main problems reside in the fragmentation of internal medicine into
      subspecialities with their own separate meetings and journals, at the expense of
      multidisciplinary sources of information on medical progress, thus widening the
      gap between the practitioners and the scientific community. Through examples, it
      is pointed out that the progression of medical knowledge follows the path from
      basic research in biochemistry, cellular biology, animal experiments, clinical
      investigation and finally clinical medicine not unidirectionally but
      bidirectionally. Thanks to the Swiss National Science Foundation, the Medical
      Schools of the five Universities and many private foundations, a considerable
      effort has been made in past decades to foster basic and clinical research,
      resulting in a most favorable position for our country on the international
      scene. There is a fear that political and administrative decision could
      jeopardize the present situation and imperil the future. Finally, citing Osler
      from his work "Aequanimitas", the author stresses that "the true test of a
      nation's life... is to be found in its intellectual and moral standards", and
      that "the measure of the value of a nation to the world is neither the bushel nor
      the barrel, but mind".

PMID- 8539581
TI  - [Generalized osteopathy with pathological fractures in a patient with long-term
      exposure to fluorine-containing plastics].
AB  - In a 68-year-old man with a painful syndrome of the lower extremities which began
      at the age of 64 years, workup revealed a generalized osteopathy with sclerosis
      of the axial skeleton and osteopenia at the extremities associated with
      pathologic fractures. The occupational history showed exposure to several
      synthetics such as vinyl chloride, polyethylene, delrine and polyamides over 30
      years. However, a presumptive connection between the skeletal disorder and the
      occupational exposure could not initially be substantiated. In a later analysis
      of the bone biopsies from 1991, a significant increase of fluorine in the tibia
      and fibula of the patient was detected and thus the diagnosis of industrial
      fluorosis established. The fluorine presumably originated from the workup of
      polytetrafluorethylene plates. A detailed analysis of the workplace is ongoing.
      The fluorosis may obviously appear as a variable skeletal disease. The clinical
      picture of fluorosis is incompletely described in most of the German textbooks.
      It calls for an extended description of the X-ray findings associated with
      fluorosis and a new definition of the disease.

PMID- 8539580
TI  - [HIV and pregnancy].
AB  - Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing
      nationwide study named "HIV and Pregnancy" financed by the Swiss Federal Office
      of Health (No. 90-7007 and 93-7131). Of a total of 228 recorded pregnancies 154
      continued to parturition. Until now it has been definitively established whether
      or not 89 offsprings have been infected with HIV by their mothers. According to
      clinical and immunological findings most of the pregnant women are still in
      early, stable stages of HIV-infection (stages II and III of the CDC
      classification system in 94% of the subjects; mean CD4-cell count around
      600/microliters). HIV infection was the consequence of an intravenous substance
      abuse in two thirds of the women. Detailed interviews revealed an alarming
      negligence with regard to compliance with safer sex recommendations and
      contraception. Advisory services of specialized AIDS information centers have
      very rarely been called on. In our group, the vertical transmission rate shows a
      statistically significant correlation with low maternal anti-HIV-p24 antibody
      titers, high serum neopterin- and IgA-concentrations, and also with the use of
      forceps and vacuum in vaginal delivery. Maternal substance abuse but not HIV
      infection itself resulted in an incidence of preterm deliveries roughly twice as
      high as in the normal Swiss population.

PMID- 8539582
TI  - [Physiology and pathophysiology of sleep].
AB  - Human sleep is characterized by the cyclic occurrence of nonREM and REM periods
      and by distinct patterns of nocturnal hormone secretion. A host of factors may
      result in disturbed sleep, including normal aging and depression. In both states,
      similar changes in sleep-endocrine activity occur, including decreases in slow
      wave sleep and in growth hormone secretion. Preclinical investigations and
      studies by our laboratory in young and elderly normal controls and in patients
      with depression demonstrate that neuropeptides play a key role in sleep
      regulation. As an example, growth hormone-releasing hormone (GHRH) is a common
      stimulus of slow wave sleep and growth hormone release, whereas corticotropin
      releasing hormone (CRH) exerts opposite effects. We suggest that an imbalance of
      both peptides in favor of CRH contributes to changes in sleep-endocrine activity
      during depression and aging.

PMID- 8539583
TI  - [Sleep disorders: diagnosis and treatment].
AB  - Disturbed or inadequate sleep is a frequent complaint with a great impact on
      daily functions and an often chronic course requiring adequate treatment. To
      choose an appropriate therapy it is necessary to develop a useful, reliable,
      valid and specific diagnostic procedure. Primary care physicians can recognize
      and treat most sleep disorders. For special diagnostic cases sleep centers are
      recommended. Sleep disorders may be managed by adequate pharmacological as well
      as nonpharmacological treatment. Besides specific pharmacological means,
      education in sleep/wake physiology and hygiene and several psychotherapeutic
      strategies may be valuable.

PMID- 8539584
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Diagnostic use of
      a new adrenostatic agents. 1959].

PMID- 8539585
TI  - The bell curve: a statement.

PMID- 8539586
TI  - Genetic patents.

PMID- 8539587
TI  - Explaining "linguistic features" of noncoding DNA.

PMID- 8539588
TI  - AIDS trials take on peer review.

PMID- 8539589
TI  - Impasse puts NIH grants on hold.

PMID- 8539590
TI  - Giving language skills a boost.

PMID- 8539591
TI  - Obesity: leptin receptor weighs in.

PMID- 8539592
TI  - A second breast cancer susceptibility gene is found.

PMID- 8539594
TI  - New skull turns up in northeast Africa.

PMID- 8539593
TI  - Flexing muscle with just one amino acid.

PMID- 8539595
TI  - Sperm protein makes its mark upon the worm embryo.

PMID- 8539596
TI  - Putting a new spin on spider silk.

PMID- 8539597
TI  - Ecdysis control sheds another layer.

PMID- 8539598
TI  - Stardust in the laboratory.

PMID- 8539599
TI  - Supported membranes: scientific and practical applications.
AB  - Scientific and practical applications of supported lipid-protein bilayers are
      described. Membranes can be covalently coupled to or separated from solids by
      ultrathin layers of water or soft polymer cushions. The latter systems maintain
      the structural and dynamic properties of free bilayers, forming a class of models
      of biomembranes that allow the application of a manifold of surface-sensitive
      techniques. They form versatile models of low-dimensionality complex fluids,
      which can be used to study interfacial forces and wetting phenomena, and enable
      the design of phantom cells to explore the interplay of lock-and-key forces (such
      as receptor-ligand binding) and universal forces for cell adhesion. Practical
      applications are the design of (highly selective) receptor surfaces of biosensors
      on electrooptical devices or the biofunctionalization of inorganic solids.

PMID- 8539600
TI  - Criticality and parallelism in combinatorial optimization.
AB  - Local search methods constitute one of the most successful approaches to solving
      large-scale combinatorial optimization problems. As these methods are
      increasingly parallelized, optimization performance initially improves but then
      abruptly degrades to no better than that of random search beyond a certain point.
      The existence of this transition is demonstrated for a family of generalized spin
      glass models and the traveling salesman problem. Finite-size scaling is used to
      characterize size-dependent effects near the transition, and analytical insight
      is obtained through a mean-field approximation.

PMID- 8539601
TI  - Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung
      infections.
AB  - Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomonas
      aeruginosa lung infections. Cultured human airway epithelial cells expressing the
      delta F508 allele of the cystic fibrosis transmembrane conductance regulator
      (CFTR) were defective in uptake of P. aeruginosa compared with cells expressing
      the wild-type allele. Pseudomonas aeruginosa lipopolysaccharide (LPS)-core
      oligosaccharide was identified as the bacterial ligand for epithelial cell
      ingestion; exogenous oligosaccharide inhibited bacterial ingestion in a neonatal
      mouse model, resulting in increased amounts of bacteria in the lungs. CFTR may
      contribute to a host-defense mechanism that is important for clearance of P.
      aeruginosa from the respiratory tract.

PMID- 8539602
TI  - Direct observation of protein solvation and discrete disorder with experimental
      crystallographic phases.
AB  - A complete and accurate set of experimental crystallographic phases to a
      resolution of 1.8 angstroms was obtained for a 230-residue dimeric fragment of
      rat mannose-binding protein A with the use of multiwavelength anomalous
      dispersion (MAD) phasing. An accurate image of the crystal structure could thus
      be obtained without resort to phases calculated from a model. Partially reduced
      disulfide bonds, local disorder, and differences in the mobility of chemically
      equivalent molecules are apparent in the experimental electron density map. A
      solvation layer is visible that includes well-ordered sites of hydration around
      polar and charged protein atoms, as well as diffuse, partially disordered solvent
      shells around exposed hydrophobic groups. Because the experimental phases and the
      resulting electron density map are free from the influence of a model, they
      provide a stringent test of theoretical models of macromolecular solvation,
      motion, and conformational heterogeneity.

PMID- 8539603
TI  - Temporal processing deficits of language-learning impaired children ameliorated
      by training.
AB  - Children with language-based learning impairments (LLIs) have major deficits in
      their recognition of some rapidly successive phonetic elements and nonspeech
      sound stimuli. In the current study, LLI children were engaged in adaptive
      training exercises mounted as computer "games" designed to drive improvements in
      their "temporal processing" skills. With 8 to 16 hours of training during a 20
      day period, LLI children improved markedly in their abilities to recognize brief
      and fast sequences of nonspeech and speech stimuli.

PMID- 8539604
TI  - Language comprehension in language-learning impaired children improved with
      acoustically modified speech.
AB  - A speech processing algorithm was developed to create more salient versions of
      the rapidly changing elements in the acoustic waveform of speech that have been
      shown to be deficiently processed by language-learning impaired (LLI) children.
      LLI children received extensive daily training, over a 4-week period, with
      listening exercises in which all speech was translated into this synthetic form.
      They also received daily training with computer "games" designed to adaptively
      drive improvements in temporal processing thresholds. Significant improvements in
      speech discrimination and language comprehension abilities were demonstrated in
      two independent groups of LLI children.

PMID- 8539605
TI  - Molecular orientation and two-component nature of the crystalline fraction of
      spider dragline silk.
AB  - The molecular origin of the exceptional mechanical properties of spider silk is
      unclear. This paper presents solid-state 2H nuclear magnetic resonance data from
      unoriented, oriented, and supercontracted fibers, indicating that the crystalline
      fraction of dragline silk consists of two types of alanine-rich regions, one that
      is highly oriented and one that is poorly oriented and less densely packed. A new
      model for the molecular-level structure of individual silk molecules and their
      arrangement in the fibers is proposed. These data suggest that it will be
      necessary to control the secondary structure of individual polymer molecules in
      order to obtain optimum properties in bio-inspired polymers.

PMID- 8539606
TI  - Identification of ecdysis-triggering hormone from an epitracheal endocrine
      system.
AB  - Developing insects repeatedly shed their cuticle by means of a stereotyped
      behavior called ecdysis, thought to be initiated by the brain peptide eclosion
      hormone. Here an ecdysis-triggering hormone, Mas-ETH, is described from the
      tobacco hornworm Manduca sexta. Mas-ETH contains 26 amino acids and is produced
      by a segmentally distributed endocrine system of epitracheal glands (EGs). The
      EGs undergo a marked reduction in volume, appearance, and immunohistochemical
      staining during ecdysis, at which time Mas-ETH is found in the hemolymph.
      Injection of EGs extract or synthetic Mas-ETH into pharate larvae, pupae, or
      adults initiates preecdysis within 2 to 10 minutes, followed by ecdysis.
      Sensitivity to injected Mas-ETH appears much earlier before ecdysis and occurs
      with shorter latency than that reported for eclosion hormone. The isolated
      central nervous system responds to Mas-ETH, but not to eclosion hormone, with
      patterned motor bursting corresponding to in vivo preecdysis and ecdysis. Mas-ETH
      may be an immediate blood-borne trigger for ecdysis through a direct action on
      the nervous system.

PMID- 8539607
TI  - Collaboration and data sharing: continued.

PMID- 8539608
TI  - When Federal science stopped.

PMID- 8539609
TI  - Med schools receive Hughes windfall.

PMID- 8539611
TI  - Cancer charity falls afoul of audit court.

PMID- 8539610
TI  - Guarding against premature birth.

PMID- 8539613
TI  - Selector genes, polymorphisms, and evolution.

PMID- 8539612
TI  - Genetic clues to Alzheimer's disease.

PMID- 8539614
TI  - Lord of the rings: GroES structure.

PMID- 8539615
TI  - Cation-pi interactions in chemistry and biology: a new view of benzene, Phe, Tyr,
      and Trp.
AB  - Cations bind to the pi face of an aromatic structure through a surprisingly
      strong, non-covalent force termed the cation-pi interaction. The magnitude and
      generality of the effect have been established by gas-phase measurements and by
      studies of model receptors in aqueous media. To first order, the interaction can
      be considered an electrostatic attraction between a positive charge and the
      quadrupole moment of the aromatic. A great deal of direct and circumstantial
      evidence indicates that cation-pi interactions are important in a variety of
      proteins that bind cationic ligands or substrates. In this context, the amino
      acids phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp) can be viewed as
      polar, yet hydrophobic, residues.

PMID- 8539616
TI  - Immunology taught by viruses.
AB  - The survival of viruses depends on the survival of susceptible hosts. The
      vertebrate immune system and viruses have therefore coevolved complementary
      facets. Evidence from various balanced virus-host relationships illustrates that
      immunological specificity and memory may best be defined biologically and that
      the mature immune system does not discriminate between "self" and "nonself."
      Rather, B cells distinguish antigen patterns, whereas T cell responses depend on
      localization, transport, and kinetics of antigen within lymphatic organs.

PMID- 8539617
TI  - Functional evidence for indirect recognition of G.U in tRNA(Ala) by alanyl-tRNA
      synthetase.
AB  - The structural features of the G.U wobble pair in Escherichia coli alanine
      transfer RNA (tRNA(Ala)) that are associated with aminoacylation by alanyl-tRNA
      synthetase (AlaRS) were investigated in vivo for wild-type tRNA(Ala) and mutant
      tRNAs with G.U substitutions. tRNA(Ala) with G.U, C.A, or G.A gave similar
      amounts of charged tRNA(Ala) and supported viability of E. coli lacking
      chromosomal tRNA(Ala) genes. tRNA(Ala) with G.C was inactive. Recognition of G.U
      by AlaRS thus requires more than the functional groups on G.U in a regular helix
      and may involve detection of a helical distortion.

PMID- 8539618
TI  - A role for CD81 in early T cell development.
AB  - Early stages of T cell development are thought to include a series of coordinated
      interactions between thymocytes and other cells of the thymus. A monoclonal
      antibody specific for mouse CD81 was identified that blocked the appearance of
      alpha beta but not gamma delta T cells in fetal organ cultures initiated with day
      14.5 thymus lobes. In reaggregation cultures with CD81-transfected fibroblasts,
      CD4-CD8- thymocytes differentiated into CD4+CD8+ T cells. Thus, interactions
      between immature thymocytes and stromal cells expressing CD81 are required and
      may be sufficient to induce early events associated with T cell development.

PMID- 8539619
TI  - Effect of polymorphism in the Drosophila regulatory gene Ultrabithorax on
      homeotic stability.
AB  - Development is buffered against unpredictable environmental and genetic effects.
      Here, a molecular genetic analysis of one type of developmental homeostasis, the
      establishment of thoracic segmental identity under the control of the
      Ultrabithorax (Ubx) gene in Drosophila melanogaster, is presented. Flies were
      artificially selected for differential sensitivity to the induction of bithorax
      phenocopies by ether vapor. The experiments demonstrated that increased
      sensitivity to ether correlated with a loss of expression of UBX in the third
      thoracic imaginal discs and that a significant proportion of the genetic
      variation for transcriptional stability can be attributed to polymorphism in the
      Ubx gene.

PMID- 8539620
TI  - Structure of the heat shock protein chaperonin-10 of Mycobacterium leprae.
AB  - Members of the chaperonin-10 (cpn10) protein family, also called heat shock
      protein 10 and in Escherichia coli GroES, play an important role in ensuring the
      proper folding of many proteins. The crystal structure of the Mycobacterium
      leprae cpn10 (Ml-cpn10) oligomer has been elucidated at a resolution of 3.5
      angstroms. The architecture of the Ml-cpn10 heptamer resembles a dome with an
      oculus in its roof. The inner surface of the dome is hydrophilic and highly
      charged. A flexible region, known to interact with cpn60, extends from the lower
      rim of the dome. With the structure of a cpn10 heptamer now revealed and the
      structure of the E. coli GroEL previously known, models of cpn10:cpn60 and
      GroEL:GroES complexes are proposed.

PMID- 8539621
TI  - Protection against osmotic stress by cGMP-mediated myosin phosphorylation.
AB  - Conventional myosin functions universally as a generator of motive force in
      eukaryotic cells. Analysis of mutants of the microorganism Dictyostelium
      discoideum revealed that myosin also provides resistance against high external
      osmolarities. An osmo-induced increase of intracellular guanosine 3',5'
      monophosphate was shown to mediate phosphorylation of three threonine residues on
      the myosin tail, which caused a relocalization of myosin required to resist
      osmotic stress. This redistribution of myosin allowed cells to adopt a spherical
      shape and may provide physical strength to withstand extensive cell shrinkage in
      high osmolarities.

PMID- 8539622
TI  - Regulation of PHO4 nuclear localization by the PHO80-PHO85 cyclin-CDK complex.
AB  - PHO4, a transcription factor required for induction of the PHO5 gene in response
      to phosphate starvation, is phosphorylated by the PHO80-PHO85 cyclin-CDK (cyclin
      dependent kinase) complex when yeast are grown in phosphate-rich medium. PHO4 was
      shown to be concentrated in the nucleus when yeast were starved for phosphate and
      was predominantly cytoplasmic when yeast were grown in phosphate-rich medium. The
      sites of phosphorylation on PHO4 were identified, and phosphorylation was shown
      to be required for full repression of PHO5 transcription when yeast were grown in
      high phosphate. Thus, phosphorylation of PHO4 by PHO80-PHO85 turns off PHO5
      transcription by regulating the nuclear localization of PHO4.

PMID- 8539623
TI  - Direct physical measure of conformational rearrangement underlying potassium
      channel gating.
AB  - In response to membrane depolarization, voltage-gated ion channels undergo a
      structural rearrangement that moves charges or dipoles in the membrane electric
      field and opens the channel-conducting pathway. By combination of site-specific
      fluorescent labeling of the Shaker potassium channel protein with voltage
      clamping, this gating conformational change was measured in real time. During
      channel activation, a stretch of at least seven amino acids of the putative
      transmembrane segment S4 moved from a buried position into the extracellular
      environment. This movement correlated with the displacement of the gating charge,
      providing physical evidence in support of the hypothesis that S4 is the voltage
      sensor of voltage-gated ion channels.

PMID- 8539624
TI  - Activation of ventrolateral preoptic neurons during sleep.
AB  - The rostral hypothalamus and adjacent basal forebrain participate in the
      generation of sleep, but the neuronal circuitry involved in this process remains
      poorly characterized. Immunocytochemistry was used to identify the FOS protein,
      an immediate-early gene product, in a group of ventrolateral preoptic neurons
      that is specifically activated during sleep. The retrograde tracer cholera toxin
      B, in combination with FOS immunocytochemistry, was used to show that sleep
      activated ventrolateral preoptic neurons innervate the tuberomammillary nucleus,
      a posterior hypothalamic cell group thought to participate in the modulation of
      arousal. This monosynaptic pathway in the hypothalamus may play a key role in
      determining sleep-wake states.

PMID- 8539625
TI  - Plasmodium hemozoin formation mediated by histidine-rich proteins.
AB  - The digestive vacuole of Plasmodium falciparum is the site of hemoglobin
      degradation, heme polymerization into crystalline hemozoin, and antimalarial drug
      accumulation. Antibodies identified histidine-rich protein II (HRP II) in
      purified digestive vacuoles. Recombinant or native HRP II promoted the formation
      of hemozoin, and chloroquine inhibited the reaction. The related HRP III also
      polymerized heme, and an additional HRP was identified in vacuoles. It is
      proposed that after secretion by the parasite into the host erythrocyte cytosol,
      HRPs are brought into the acidic digestive vacuole along with hemoglobin. After
      hemoglobin proteolysis, HRPs bind the liberated heme and mediate hemozoin
      formation.

PMID- 8539626
TI  - Polypropylene tube surfaces may induce denaturation and multimerization of DNA.

PMID- 8539627
TI  - Hepatic fibrosis in Ahr-/- mice.

PMID- 8539628
TI  - Hodgkin's disease: is staging laparotomy still necessary?

PMID- 8539629
TI  - Introduction: adjuvant and neoadjuvant therapy.

PMID- 8539630
TI  - Adjuvant and neoadjuvant treatment for primary brain tumors in adults.

PMID- 8539631
TI  - Adjuvant and neoadjuvant treatment of head and neck cancers: the next chapter.

PMID- 8539632
TI  - Adjuvant systemic therapy for breast cancer.

PMID- 8539633
TI  - Perioperative therapy of non-small cell lung cancer: a review of adjuvant and
      neoadjuvant approaches.

PMID- 8539634
TI  - Adjuvant therapy of upper gastrointestinal tract cancers.

PMID- 8539635
TI  - Adjuvant therapy of colon cancer.

PMID- 8539636
TI  - Adjuvant and neoadjuvant treatment of rectal cancer.

PMID- 8539637
TI  - Neoadjuvant and adjuvant chemotherapy for invasive bladder cancer.
AB  - Patients with muscle-invasive transitional cell carcinoma of the bladder are at
      high risk of systemic relapse following primary therapy. Several randomized
      trials of neoadjuvant and adjuvant chemotherapy suggest that chemotherapy
      administered before or after primary therapy may improve the disease-free
      survival of patients with invasive bladder cancer. The effects of neoadjuvant and
      adjuvant chemotherapy on long-term survival remain controversial. Potential
      differences in the long-term outcome of patients treated with neoadjuvant and
      adjuvant chemotherapy are not known. The only randomized trial comparing these 2
      approaches showed no difference in survival with short median follow-up.
      Treatment recommendations for an individual patient require consideration of the
      relative advantages and disadvantages of chemotherapy administered before or
      after primary therapy. Recommendations regarding the optimal treatment of
      patients with invasive bladder cancer await the results of ongoing randomized
      trials. Because the use of adjuvant and neoadjuvant chemotherapy in patients with
      invasive bladder cancer represents a promising but unproven approach, physicians
      should encourage patients with invasive bladder cancer to enroll in clinical
      trials.

PMID- 8539638
TI  - Adjuvant systemic therapy of prostate cancer.

PMID- 8539639
TI  - Adjuvant chemotherapy for patients with stage II nonseminomatous testis cancer.

PMID- 8539640
TI  - Adjuvant therapy for cutaneous melanoma.

PMID- 8539641
TI  - A change in expectations.

PMID- 8539642
TI  - Computed tomography imaging of focal hepatic lesions.

PMID- 8539643
TI  - Ultrasound of focal hepatic lesions.
AB  - Hepatic sonography is useful in characterizing many focal liver lesions (Tables 2
      6). It is safe, portable, and relatively inexpensive. With the development of
      color Doppler imaging, power Doppler imaging, and intravenous-ultrasound contrast
      agents, the ability to detect and precisely diagnose a focal hepatic lesion may
      be improved.

PMID- 8539644
TI  - Magnetic resonance imaging of focal liver lesions.

PMID- 8539645
TI  - Angiographic evaluation of focal liver masses.

PMID- 8539647
TI  - [The gene plays in a concert. Interview with Dr. H. Muller by Klaus Reinhardt)].

PMID- 8539646
TI  - Nuclear imaging of solid hepatic masses.
AB  - This review has focused on the unique role of radionuclide scintigraphy in
      characterization of hepatic mass lesions. Radionuclide scintigraphy, unlike most
      other imaging modalities, is based on specific physiological and biochemical
      properties of each pathological entity that affects the liver. Hepatic
      scintigraphy, with its widespread availability, noninvasive nature, and
      relatively low cost is a powerful adjunct to other imaging techniques in the
      investigation of hepatic mass lesions. We have reviewed clinical presentation and
      characteristic findings of most hepatic lesions and have described reported
      findings with all available imaging modalities with particular emphasis on
      hepatic scintigraphy (Table 1) as well as a suggested algorithm for workup of
      solid hepatic masses (Fig 6). Additionally, the role of newer, more specialized
      techniques including PET scanning, 123I-labeled VIP, and 111In-labeled DTPA-D-Phe
      octreotide scanning are reviewed. Hepatic nuclear scintigraphy continues to play
      an important role in the management of patients with solid hepatic masses.

PMID- 8539648
TI  - [Dr. Heinrich Rellstab, pioneer in medical genealogic research in Switzerland].

PMID- 8539649
TI  - [Prenatal diagnosis].
AB  - A growing number of methods for the in-utero diagnosis of fetal disease became
      available during recent decades, mainly due to rapid advances in ultrasound
      technology and laboratory methods. Exclusion of fetal aneuploidy in pregnancies
      of women beyond 34 years is still by far the most common reason for an invasive
      procedure event at a time when the number of diagnosable inborn errors of
      metabolism and monogenetic disorders is increasing rapidly. Great efforts have
      been made to improve the poor predictive value of maternal age as an indicator
      for an increased risk for fetal aneuploidy. Maternal serum screening using
      various parameters [e.g. AFP, hCG, uE3] has been found effective in identifying
      the majority of pregnancies with Down syndrome in the second trimester. Current
      research goals are the optimal choice of markers and the introduction of maternal
      serum screening in the first trimester of pregnancy. Ultrasound is another
      suitable tool to identify pregnancies at high risk for aneuploidy at least in the
      hands of experienced operators. The diagnostic use of fetal cells in the maternal
      circulation is presently investigated in a large collaborative trial. Second
      trimester amniocentesis still is the most widely applied invasive technique in
      pregnancies with maternal age related risks for fetal aneuploidy. Safety and
      diagnostic accuracy are well established and amniotic fluid can easily be
      shipped. Without major changes in conventional sampling and laboratory techniques
      the procedure can be performed at 13 weeks of gestation and later. The safety and
      efficacy of first-trimester amniocentesis has still to be established in larger
      series. First-trimester chorionic villus sampling is a well-established
      alternative to amniocentesis with comparable procedure-related risks. It is the
      method of first choice in pregnancies at high risk for aneuploidy, inborn errors
      of metabolism and monogenic disorders, since uncultured villi can be used for a
      rapid diagnosis. Placental biopsy should also be considered in the second and
      third trimester of pregnancy for these indications whenever time is a critical
      issue. Fetal blood obtained by ultrasound-guided cordocentesis has successfully
      been used for the diagnosis of fetal infection and is at the same time another
      good source of cells for rapid karyotyping. Other invasive procedures such as
      fetal skin or liver biopsies for electron microscopy or specific metabolic tests
      are restricted to the relatively rare instances of diseases where DNA diagnosis
      is currently not available or uninformative. Providing information on the
      different alternatives in an individual situation is one of the critical issues
      in pregnancy care today.

PMID- 8539650
TI  - [Molecular diagnosis of cystic fibrosis].
AB  - Cystic fibrosis [CF] is the most common autosomal recessively inherited disease
      in the caucasian population. Based upon the population frequency of approximately
      1 in 2000 in Switzerland, the heterozygote frequency can be calculated to be 1 in
      22. The genetic basis for CF has been shown to be mutations in the gene coding
      for an epithelial membrane chloride channel, the Cystic Fibrosis Transmembrane
      conductance Regulator [CFTR]. To date over 500 mutations have been characterized
      in this gene. The frequency of specific mutations varies amongst different ethnic
      groups. In Switzerland 8 mutations have been shown to account for approximately
      90% of all CF causing alleles. The cloning and molecular characterization of the
      CFTR gene has lead to a major breakthrough in the understanding of the
      biochemical basis of CF pathogenesis. Advances through analysis of cellular and
      animal model systems have made a genetic based therapy for CF a real possibility.

PMID- 8539651
TI  - [Fragile X syndrome: clinical and molecular genetics correlations].
AB  - The fragile X form of mental retardation is presently recognized as the most
      frequent hereditable cause of mental impairment. The estimated frequency among
      males is 1 in 1250, and 1 in 2000 among females. Beside mental impairment and
      behavioural disturbance with hyperactivity and autistic features, the patients
      are characterized by morphological anomalies, such as an oblong face, broad,
      rectangular chin, large protruding ears and macro-orchidism. A less severe
      clinical expression can be found among females heterozygotes of the disorder,
      manifesting mainly as learning disability. The disorder is associated with the
      expression of a fragile site at Xq27.3 under conditions of folate depletion in
      the chromosome culture medium. The molecular mechanism is based on the expansion
      of a trinucleotide repeat [CCG]n in the promoter region of the FMR1 gene
      resulting in methylation of the gene. The trinucleotide repeat shows variable
      lengths of 6 to 53 repeats in the general population, 60 to 200 repeats in
      carriers of a premutation and over 200 repeats in patients with fragile X
      syndrome.

PMID- 8539652
TI  - [Diagnostic studies in patients and relatives with hereditary neuromuscular
      diseases].
AB  - Preclinical and prenatal diagnosis as well as detection of healthy carriers is
      now theoretically possible for more than 200 monogenic inherited neurological and
      neuromuscular diseases and practically performed in many of them. However, it has
      to be made a condition, that the diagnosis in the index patient is secured by all
      clinical and laboratory methods available today, and that the specific mutation
      has been localized or even sequenced, and of course the families must give their
      full consent to the examinations. It is important to submit material for the
      different laboratory investigations from patients and their relatives as early as
      possible [biopsies, blood samples for DNA, etc.], at least for rapidly
      progressive diseases with a poor prognosis. In order to obtain very high
      probabilities in diagnostic predictions a family has to be examined either with
      mutation-specific DNA-probes and/or with probes for closely linked polymorphic
      DNA-markers. This requires a close cooperation between genetic services and DNA
      laboratories on the one hand and the family doctors, specialists and clinics on
      the other. Specific strategies are discussed for hereditary sensory and motor
      neuropathy [HMSN la or Charcot-Marie-Tooth disease], Duchenne und Becker muscular
      dystrophy and childhood spinal muscular atrophies.

PMID- 8539653
TI  - [Huntington's chorea: clinical aspects, genetics and current diagnosis].
AB  - Huntington's disease is a late manifesting autosomal dominant neurodegenerative
      disorder. It is characterized by motor disturbance, loss of cognitive functions
      and psychiatric manifestations. The disease causing mutation, an unstable DNA
      sequence in the coding region of the Huntington gene on chromosome 2p, has
      recently been identified. A trinucleotide [CAG] repeat is expanded over the
      normal range and can be easily detected by standard laboratory methods. Accurate
      genetic testing can now be offered in clinically questionable cases and to
      presymptomatic subjects at risk for Huntington's disease. Furthermore, there is a
      correlation between the size of the expanded CAG repeat and the age of onset in
      affected individuals. The predictive value of this correlation, however, is
      limited due to the range of onset ages found at a given repeat length in large
      series of patients. Expanded triplet repeats exhibit a marked instability
      especially in male meiosis with a tendency to further increase during
      transmission over the generations. This is likely to be the molecular mechanism
      explaining anticipation, as well as the occurrence of juvenile cases and new
      mutations.

PMID- 8539654
TI  - [Genetic predisposition for Alzheimer's disease].
AB  - Alzheimer's disease comprises senile and presenile dementia. Aetiologically the
      disease is heterogeneous but has common clinical and pathological
      characteristics. Furthermore, in patients with a family history of dementia, its
      incidence is higher than in the general population. In families which inherit
      early-onset forms of the disease in an autosomal dominant fashion, several
      apparently pathogenic mutations were identified in three different genes.
      Dominant hereditary factors are not known for the much more common late-onset
      forms of Alzheimer's dementia. There are, however, genetic risk factors which
      contribute to the development of the disease. To date just one of these factors,
      the apolipoprotein E allele epsilon 4 has been definitively identified. Genetic
      testing can currently only be done for prognosis of the early onset but not the
      late onset forms of the disease.

PMID- 8539655
TI  - [Familial colorectal and breast carcinoma--genetic counseling and presymptomatic
      diagnosis].
AB  - Several types of hereditary cancer can be prevented from progressing to advanced
      stages by regular surveillance of the person at risk and hence by the early
      treatment of a developing neoplasia. Genetic counselling of such patients and
      their relatives is therefore an important task whose value often remains
      unrecognized. This is especially true for the common forms of hereditary cancer
      such as breast and colorectal cancer, which aggregate in up to 5% of all patients
      according to the rules of autosomal-dominant inheritance. Preventive measures are
      particularly promising in the case of familial cancer because persons at risk are
      motivated to seek medical help. Genetic counselling is a multifaceted process and
      involves more than an accurate diagnosis and risk estimate. The counseled patient
      expects and deserves an open and reasonable answer to his questions about the
      implications of his/her cancer predisposition or his family history. Accurate
      diagnosis of the underlying susceptibility is the cornerstone of genetic
      counselling because most cancers seem to have multiple causes. Different genes
      located on different chromosomes can independently give rise to the same
      malignancy. Besides heterogeneity, presymptomatic testing for inherited
      susceptibilities to cancer raises many issues including therapy, access, intense
      anxiety, and discrimination.

PMID- 8539656
TI  - [Application of genetic principles to the causal assessment of atherosclerosis].
AB  - The pathophysiological mechanisms responsible for the development of
      atherosclerosis are complex and influenced by numerous genetic factors
      [polygenic] as well as environmental factors. Specific disorders caused by single
      gene mutations [monogenic] may considerably enhance the risk for atherosclerosis.
      In such cases, other genes or environmental factors are often secondary
      importance. A detailed family history including a pedigree analysis may lead to
      the correct diagnosis; molecular genetic methods can confirm the clinical
      diagnosis. The association between a particular gene [candidate gene] and a
      disorder characterized by an increased risk for atherosclerosis can be verified
      indirectly by linkage analysis or directly by the detection of the gene mutation
      causing the disorder. Both approaches are based on the fact that a polymorphism
      used as a marker for a gene locus or a mutation responsible for a particular
      disorder may destroy or create a restriction site [restriction fragment length
      polymorphism, RFLP] or may modify the electrophoretic mobility of a fragment
      amplified by the polymerase chain reaction [PCR]. The latter property is the
      basis of the single-strand conformation polymorphism [SSCP] technique, followed
      by sequencing for the exact localization of the polymorphism or the mutation.
      Using these methods, other family members carrying the underlying gene defect can
      be identified and treated before the manifestation of their atherosclerotic
      lesions.

PMID- 8539657
TI  - [Blood relationship].
AB  - In every-day medical practice, blood relationship of spouses hardly ever play an
      important part. Mainly for genetic counselors and pediatricians the question of
      consanguinity of a child's parents arises when either a rare, often hereditary,
      disorder is diagnosed for the first time in a family, or potential parents want
      information on the risk for hereditary diseases. A probability calculus based on
      the corresponding hereditary factors of the joint ancestors establishes how
      likely homozygotes for hereditary diseases among the offspring of [blood]-related
      spouses - often cousins of the first or second degree - is. Furthermore, proof of
      the parents' consanguinity may explain a child's unexpected hereditary disease
      [especially autosomal recessive disorders] and, at the same time, it means a
      higher risk of repetition for the affected child's desired siblings. Incest
      represents a special form of genetic risk; this question arises either in
      connection with the adoption of a child, which was conceived by an incestuous
      couple, or with such a child's own family planning later on. Even the parents'
      descent from an ethnically, politically, religiously or linguistically isolated
      background may gave a similar impact on the appearance of hereditary disorders:
      an accumulation of rare genes has to be taken into account; factors causing
      disorders have to be expected among these genes, too. In the following, all major
      aspects of the situations described above will be given in detail.

PMID- 8539658
TI  - [Gene therapy, gene pharmacology: concepts, fields of application, problems].
AB  - Gene therapy represents a new strategy for the treatment of genetic disorders, of
      viral infections and of cancer. At the present time it is still an experimental
      phase. However, it is assumed that gene therapy will belong to the spectrum of
      established therapeutic procedure in the next century. Gene pharmacology is an
      extension of traditional pharmacology. Chemical agents will be to given to
      patients with viral infections with the goal to impair the expression of the
      viral genes. Not only ethical aspects but also biological and medical
      considerations are hurdles in the realisation of germ-line gene therapy.

PMID- 8539659
TI  - [Family anamnesis--pedigree analysis].
AB  - A thoroughly compiled medical family history is a cheap and beneficial component
      of the patient's work-up which gives clues for the identification and
      classification of susceptibilities to genetic disorders. The information can
      easily be summarized in diagrammatic form. The pedigree is drawn up in accordance
      with loosely standardize rules whose symbols are described in the accompanying
      article.

PMID- 8539661
TI  - Successful stenting of a pulmonary arterial stenosis after a single lung
      transplant.
AB  - A 44 year old patient with end stage idiopathic pulmonary fibrosis underwent
      single left lung transplantation. A perfusion lung scan performed 13 days after
      transplantation revealed deficient perfusion in the transplanted lung. Pulmonary
      angiography showed severe pulmonary artery anastomotic stenosis. Percutaneous
      insertion of a balloon expandable stent improved both pulmonary perfusion and
      respiratory function.

PMID- 8539662
TI  - Pulmonary arterial aneurysm presenting as an endobronchial mass.
AB  - The case is presented of a 25 year old man with haemoptysis who exsanguinated
      following endoscopic fine needle aspiration of an endobronchial mass. Necroscopic
      examination revealed an aneurysm of the proximal left pulmonary artery.

PMID- 8539660
TI  - Cysteinyl leukotrienes in asthma: current state of therapeutic evaluation.

PMID- 8539663
TI  - Preoperative diagnosis of a pulmonary artery sarcoma.
AB  - A pulmonary artery sarcoma was diagnosed preoperatively by magnetic resonance
      imaging enhanced with gadolinium and confirmed by percutaneous computed
      tomographic guided needle biopsy. Accurate preoperative diagnosis allowed planned
      curative surgery with removal of the right ventricular outflow tract and
      reconstructive surgery using a cryopreserved homograft.

PMID- 8539664
TI  - Chronic lung abscess due to Pasteurella multocida.
AB  - A case of chronic lung abscess due to Pasteurella multocida presenting as a
      solitary pulmonary mass with a computed tomographic appearance suggestive of
      malignancy is described.

PMID- 8539665
TI  - Chylothorax due to Mycobacterium tuberculosis.
AB  - Chylothorax in an adult is a rare cause of pleural effusion. Mycobacterium
      tuberculosis may cause chylous effusion, but usually in association with
      extensive intrapulmonary involvement. A case of chylothorax is presented in which
      M tuberculosis was isolated from the pleural fluid and was the only intrathoracic
      manifestation of tuberculosis.

PMID- 8539666
TI  - Asthma morbidity and mortality in New Zealand.

PMID- 8539667
TI  - Asthma morbidity and mortality in New Zealand.

PMID- 8539668
TI  - T cell receptor genetics, autoimmunity and asthma.

PMID- 8539670
TI  - Diagnosis of pulmonary embolism.

PMID- 8539669
TI  - High altitude pulmonary oedema: still a place for controversy?

PMID- 8539671
TI  - Effect of readmissions on increasing hospital admissions for asthma in children.
AB  - BACKGROUND: Previous studies have reported increases in the number of hospital
      admissions for asthma in children. The aim of the present study was to examine
      the effect of readmissions on these increased hospital admissions and to
      investigate gender differences in asthma readmissions. METHODS: The Provincial
      Government of Saskatchewan provides universal health care to its residents.
      Hospital admissions data for asthma were obtained from the Saskatchewan Health
      Department for all 134 hospitals in the province between 1980 and 1989. Age
      specific and sex-specific hospital admission rates for asthma were calculated for
      each calendar year using first admissions and all admissions. The ratio between
      the number of readmissions and all admissions in a year was defined as the
      readmission rate for that year. RESULTS: Although rates based on all admissions
      for asthma were greater than rates based on first admissions, trends and sex
      differences were similar for the two rates. Despite the higher hospital admission
      rates for boys aged 10-14 years, girls in this age group had higher readmission
      rates for asthma from 1981 to 1989 (odds ratio (OR) 1.6 for girls; 95% confidence
      intervals (CI) 1.3 to 1.9). Similar increases were observed in readmission rates
      for asthma among children aged 5-9 years from 1985 to 1989 (OR 1.3 for girls; 95%
      CI 1.1 to 1.5). CONCLUSIONS: Readmissions for asthma do not seem to explain the
      increasing trend in hospital admissions for asthma in children. In children aged
      10-14 years girls had higher hospital readmission rates for asthma than boys, and
      further studies are required to find factors related to the increased
      readmissions among girls in this age group.

PMID- 8539672
TI  - Effects of propranolol inhalation on the diurnal increase in FEV1 and on
      propranolol airways responsiveness in atopic subjects with asthma.
AB  - BACKGROUND: Propranolol inhalation provocation tests are used to measure indirect
      airways responsiveness in the investigation of asthma. In this study the effects
      of repeated propranolol inhalation provocation tests within the same day on
      normal diurnal variation in the forced expiratory volume in one second (FEV1) and
      subsequent propranolol airways responsiveness were investigated. METHODS: Fifteen
      atopic asthmatic subjects were challenged with doubling concentrations of
      propranolol at 08.00 and 16.00 hours on the same study day and at 16.00 hours on
      a control day to exclude changes related to normal diurnal variation. RESULTS:
      Mean (SD) baseline FEV1 at 16.00 hours on the study day was 3.38 (0.23) 1,
      significantly lower than the value at 16.00 hours on the control day of 3.70
      (0.24) 1 (p = 0.001). No differences were found between the geometric mean
      provocative concentration of propranolol causing a 20% fall in FEV1 (PC20)
      measured on the study day (08.00 hours, 9.3 mg/ml; 16.00 hours, 11.3 mg/ml) and
      on the control day (16.00 hours 9.3 mg/ml). CONCLUSIONS: The results suggest that
      propranolol provocation at 08.00 hours has a long lasting effect on FEV1, thereby
      counteracting the normal diurnal increase in diameter of the airways. This makes
      propranolol challenge tests less suitable for studying indirect airways
      responsiveness in the course of one day. Because the FEV1 does not return to
      control values, it is not possible to determine whether tachyphylaxis to repeated
      propranolol challenge with a time interval of up to eight hours occurs.

PMID- 8539673
TI  - Effect of dietary sodium on airways responsiveness and its importance in the
      epidemiology of asthma: an evaluation in three areas of northern England.
AB  - BACKGROUND: Although several investigations have shown a relationship between
      asthma (or its surrogate, airways responsiveness) and dietary or urinary sodium,
      others have not, and the matter remains controversial. This "salt effect" has
      been investigated during two recent epidemiological surveys of men in northern
      England. The first assessed the possible effect on airways responsiveness of
      occupational exposure to welding fumes, and the second characterised airways
      responsiveness in two geographically distinct residential areas. Thus, three
      separate study areas/populations were involved. METHODS: Investigation 1 involved
      1059 shipyard workers aged 16-27 years who were exposed variously to welding
      fumes, and Investigation 2 involved 587 men aged 20-44 years who lived in rural
      West Cumbria or in urban Newcastle upon Tyne. In Investigation 1, a 24 hour urine
      specimen was requested from each subject with quantifiable airways responsiveness
      (PD20 < or = 6400 micrograms methacholine) and from an equal number of subjects
      without measurable airways responsiveness from the same occupational subgroup. In
      Investigation 2, every subject was asked to provide a 24 hour urine specimen.
      RESULTS: Of the men undergoing methacholine tests, satisfactory 24 hour urine
      specimens were obtained from 234 (22.1%) in Investigation 1 and 232 (39.5%) in
      Investigation 2. Analysis using multiple linear regression, multiple linear
      logistic regression, and multiple regression for censored data produced
      consistent results within each study population but conflicting results between
      them, such that there was no hint of a relationship between airways
      responsiveness and 24 hour urinary sodium excretion in the shipyard workers of
      Investigation 1 nor in the rural West Cumbrian population of Investigation 2, but
      an association was found in the urban Newcastle population of Investigation 2.
      All study populations were sufficiently large to demonstrate anticipated
      relationships between airways responsiveness and atopy, baseline FEV1, and
      (Newcastle only) age. CONCLUSIONS: If airways responsiveness is related to
      dietary sodium the relationship is not likely to be strong.

PMID- 8539674
TI  - Hospital admission rates for asthma and respiratory disease in the West Midlands:
      their relationship to air pollution levels.
AB  - BACKGROUND: A study was undertaken to determine the relationship between hospital
      admissions for asthma and all respiratory conditions in electoral wards in the
      West Midlands and ambient levels of smoke, sulphur dioxide, and nitrogen dioxide,
      and to establish whether the relationship is independent of social deprivation
      and ethnicity, and is different for young children and older individuals.
      METHODS: Data on hospital admissions for acute respiratory conditions were
      obtained by electoral ward from the West Midlands Regional Health Authority
      Information Department Korner inpatient data including asthma (ICD 493) and all
      acute respiratory disease (466, 480-486, 490-496) for the period April 1988 to
      March 1990. The population for each electoral ward, percentage of ward population
      that was from non-white ethnic groups, and Townsend deprivation score were all
      calculated from 1991 census information. Data on smoke and sulphur dioxide (SO2)
      levels were obtained for 24 wards in Birmingham, Coventry, Wolverhampton, Dudley,
      Stafford, and Burton-on-Trent, and on nitrogen dioxide (NO2) levels from 39 wards
      in the same local authority areas. All were background urban sites and most
      participated in the Warren Spring national quality control programme for SO2 and
      smoke monitoring. Indirect age-sex standardised hospitalisation rates (SHR) for
      all respiratory conditions and asthma were calculated using the 1991 rates for
      the West Midlands RHA as the standard. Multivariate regression models were used
      to assess the relationship between individual pollutants and the SHR. The
      Townsend score and percentage of the population from non-white ethnic groups were
      included in all models to adjust for ethnicity and socioeconomic deprivation.
      RESULTS: The SHR for asthma varied almost fourfold across the region, and all
      respiratory SHR showed more than three fold variation. Bivariate regression
      revealed both Townsend score and percentage of non-white individuals to be
      associated with SHR for asthma and all respiratory conditions at all ages, but
      not for children under 5 years. NO2 was associated with hospital admission rates
      for all ages including children under 5. SO2 and smoke were not associated with
      hospital admissions. Multivariate analysis including Townsend score and
      percentage of non-white subjects in the model revealed that NO2 was associated
      with hospital admission rates for all respiratory conditions only for children
      under 5. The Townsend score was associated with SHR for all respiratory
      conditions, and both the Townsend score and percentage of non-white subjects were
      associated with SHR for asthma in children under 5 in two of three models. The
      association between SHR for asthma and percentage of non-white subjects was
      negative. CONCLUSIONS: Socioeconomic deprivation, as measured by the Townsend
      score, is a significant predictor of hospital admission rates for respiratory
      disease in older individuals, and both the percentage of non-white subjects and
      the Townsend score are significant predictors of hospital admission rates for
      asthma in children. After correction for socioeconomic deprivation and ethnicity,
      background urban NO2 levels in the ward of residence are significantly associated
      with standardised hospital admission rates for all respiratory disease in
      children under 5. This may represent a causal effect of NO2 on the respiratory
      health of children, or the effect of confounding factors not corrected by use of
      the Townsend score.

PMID- 8539675
TI  - Potential for lung sound monitoring during bronchial provocation testing.
AB  - BACKGROUND: The use of lung sound monitoring during bronchial provocation testing
      has not been clearly demonstrated. The appearance of wheeze and changes in
      inspiratory breath sound intensity have been analysed and related to changes in
      spirometric parameters and to airways hyperresponsiveness. METHODS: Lung sounds
      were recorded in 38 patients undergoing a routine carbachol airway challenge
      (CAC) test. Spirometric testing was performed before and after the inhalation of
      each of five cumulative doses of 320 micrograms carbachol; a fall in forced
      expiratory volume in one second (FEV1) by 20% or more was considered as
      significant. Lung sound analysis was carried out using a computerised system.
      RESULTS: The CAC test was positive (CAC+) in 21 patients and negative (CAC-) in
      17. At the final stage of the challenge, wheeze was identified in 10 positive
      patients (48%) and in one negative patient (6%); in non-wheezers the inspiratory
      breath sound intensity decreased significantly from baseline in 11 CAC+ patients
      (mean (SD) change -35 (24%)) but not in 16 CAC- patients (mean (SD) change 5
      (24%)). In all non-wheezers a linear relationship was found between breath sound
      intensity and the squared inspiratory airflow (r = 0.53-0.92) which became looser
      after the inhalation of carbachol. CONCLUSION: When unertaking bronchial
      provocation testing the accurate identification of wheeze may prove useful in
      avoiding or shortening the test because of the presumed relationship between
      wheeze and airways hyperresponsiveness. Changes in breath sound intensity may
      also be useful, but further studies are required to define the threshold for
      significant changes in this index.

PMID- 8539676
TI  - Control of breathing in patients with limb girdle dystrophy: a controlled study.
AB  - BACKGROUND: In patients with limb girdle dystrophy the relative contribution of
      peripheral factors (respiratory muscle weakness, and lung and/or airway
      involvement) and central factors (blunted and/or inadequate chemoresponsiveness)
      in respiratory insufficiency has not yet been established. To resolve this, lung
      volumes, arterial blood gas tensions, respiratory muscle strength, breathing
      pattern and neural respiratory drive were investigated in a group of 15 patients
      with limb girdle dystrophy. An age-matched normal group was studied as a control.
      METHODS: Respiratory muscle strength was assessed as an arithmetic mean of
      maximal inspiratory (MIP) and expiratory (MEP) pressures. Breathing pattern was
      evaluated in terms of volume (ventilation VE, tidal volume VT) and time
      (respiratory frequency Rf, inspiratory time TI, expiratory time TE) components of
      the respiratory cycle. Neural respiratory drive was assessed as the mean
      inspiratory flow (VT/TI), mouth occlusion pressure (P0.1) and electromyographic
      activity (EMG) of the diaphragm (EMGd) and the intercostal parasternal (EMGp)
      muscles. In 10 of the 15 patients the responses to carbon dioxide (PCO2)
      stimulation were also evaluated. RESULTS: Most patients exhibited a moderate
      decrease in vital capacity (VC) (range 37-87% of predicted), MIP (range 23-84% of
      predicted), and/or MEP (range 13-41% of predicted). The arterial carbon dioxide
      tension (PaCO2) was increased in three patients breathing room air, while PaO2
      was normal in all. Compared with the control group Rf was higher, and VT, TI and
      TE were lower in the patients. EMGd and EMGp were higher whilst VT/TI and P0.1
      were normal in the patients. Respiratory muscle strength was inversely related to
      EMGd and EMGp. PaCO2 was found to relate primarily to VC and duration of illness,
      but not to respiratory muscle strength. During hypercapnic rebreathing delta
      VE/delta PCO2, delta VT/delta PCO2, and delta P0.1/delta PCO2 were lower than
      normal, whilst delta EMGd/delta PCO2 and delta EMGp/delta PCO2 were normal in
      most patients. A direct relation between respiratory muscle strength and delta
      VT/delta PCO2 was found. CONCLUSIONS: The respiratory muscles, especially
      expiratory ones, are weak in patients with limb girdle dystrophy. Reductions in
      respiratory muscle strength are associated with increased neural drive and
      decreased ventilatory output (delta VT/delta PCO2). The decrease in VC, together
      with the duration of disease, influence PaCO2. VC is a more useful test than
      respiratory muscle strength for following the course of limb girdle dystrophy.

PMID- 8539677
TI  - Adequacy of prescribing nasal continuous positive airway pressure therapy for the
      sleep apnoea/hypopnoea syndrome on the basis of night time respiratory recording
      variables.
AB  - BACKGROUND: The increased demand of full polysomnographic studies, not only for
      diagnostic purposes but also for continuous positive airway pressure (CPAP)
      titration, has produced long waiting lists. Simpler methods are therefore needed
      to avoid having to refer all patients for full polysomnography. The hypothesis
      that CPAP therapy for the sleep apnoea/hypopnoea syndrome (SAHS) can be performed
      exclusively on the basis of recording night time respiratory variables was
      tested. METHODS: The level of CPAP in a group of 41 patients (three women) of
      mean (SD) age 52 (10) years, body mass index 31.5 (4.4) kg/m2, and
      apnoea/hypopnoea index (AHI) 53(16) events/hour was measured. During a two week
      period CPAP titration was performed in a random order in two settings: (1) in the
      sleep laboratory using full polysomnography; and (2) in the respiratory ward
      using equipment which continuously recorded and displayed pulse oximetry,
      airflow, chest and abdominal motion, and body position. The level of CPAP was
      increased progressively until apnoea, hypopnoea, snoring, and thoraco-abdominal
      paradox disappeared. RESULTS: No differences in CPAP levels (9.34(2.2) versus
      9.68 (2.1) cm H2O) were found between full polysomnography and night time
      respiratory recordings. The accuracy of the measurement of both procedures showed
      good agreement. Only one patient showed a significant difference in CPAP level
      requirements between the two methods. CONCLUSIONS: Night time respiratory
      recording is sufficient to permit a reasonable choice of CPAP levels to abolish
      all the respiratory disturbances in most of the patients studied.

PMID- 8539678
TI  - Validation of British Thoracic Society guidelines for the diagnosis of the sleep
      apnoea/hypopnoea syndrome: can polysomnography be avoided?
AB  - BACKGROUND: The British Thoracic Society report on the diagnosis and treatment of
      the sleep apnoea/hypopnoea syndrome (SAHS) suggests that, if the pulse oximetry
      baseline oxygen saturation is above 90%, then 15 4% oxygen desaturation/hour in
      bed will diagnose SAHS requiring treatment. The diagnostic outcome of applying
      these guidelines has been studied. METHODS: One hundred patients referred to a
      district general hospital sleep clinic were recruited. After initial clinical
      assessment, overnight pulse oximetry measurements were performed, followed by
      full polysomnography at the regional laboratory. RESULTS: Sixty nine patients
      underwent both pulse oximetry and polysomnography. All 10 patients with more than
      15 4% desaturations/hour on pulse oximetry had SAHS confirmed on polysomnography
      (specificity = 100%). Twenty two patients with SAHS were misdiagnosed using pulse
      oximetry alone (sensitivity = 31%). These patients had low apnoea scores but high
      hypopnoea scores. CONCLUSIONS: The BTS pulse oximetry criteria are highly
      specific when positive (specificity = 100%), but may miss patients with the SAHS
      who have hypopnoeic episodes which cause arousal but not significant oxygen
      desaturation (sensitivity = 31%). It should be emphasised that pulse oximetry
      alone does not always give sufficient information to discriminate between those
      patients with or without SAHS. Patients with "negative" pulse oximetry and
      symptoms of SAHS should undergo polysomnography or multi-channel recording.

PMID- 8539679
TI  - Trends in mortality from tuberculosis in England and Wales: effect of age on
      deaths from non-respiratory disease.
AB  - BACKGROUND: Although mortality from tuberculosis has continued to fall in recent
      years, there has been little change in the case fatality rate for tuberculosis
      over the same period. This has previously been shown to be due to the increasing
      proportion of cases of tuberculosis occurring in the elderly. Tuberculosis
      mortality and case fatality were therefore analysed to determine if this
      disappointing trend in case fatality rate has occurred from disease in all or
      only certain sites. METHODS: A retrospective analysis of the tuberculosis
      mortality and case fatality rates in England and Wales for the period 1972-92 was
      carried out. The average annual percentage change in tuberculosis was calculated
      for each disease site and by age group and the results were compared. RESULTS:
      The analysis showed that, although the mortality rate fell steadily by 5.6% per
      annum, the case fatality rate decreased by only 0.9% (95% CI -1.7 to -0.1) per
      annum. The case fatality rate for respiratory and central nervous system disease
      declined, but no decline in tuberculosis at "other" sites was observed (1.01%
      (+2.2 to -0.2) for all age groups combined). In the group aged 75 and over,
      however, the proportion of deaths due to disease at other sites increased by 3.2%
      (2.2 to 4.3) per annum whilst in the other age groups the mortality rate
      declined. CONCLUSIONS: This analysis suggests that clinicians may be becoming
      less able to recognise non-respiratory presentations of tuberculosis,
      particularly in the elderly, and underlines the need to consider tuberculosis as
      a diagnosis to avoid delay in treatment.

PMID- 8539680
TI  - Efficiency of oxidative work performance of skeletal muscle in patients with
      cystic fibrosis.
AB  - BACKGROUND: Exercise intolerance in patients with cystic fibrosis is commonly
      attributed to reduced pulmonary and nutritional status. The possible role of
      diminished efficiency of mitochondrial oxidative phosphorylation in relation to
      skeletal muscle performance was investigated in patients with cystic fibrosis.
      METHODS: In vivo synthesis of ATP in skeletal muscle during submaximal exercise
      was studied in eight patients with cystic fibrosis aged 12-17 years, and in 19
      healthy control subjects aged 8-36 years. The intracellular pH and concentrations
      of phosphate compounds were calculated at four steady states from phosphorus-31
      labelled nuclear magnetic resonance spectroscopy measurements in the forearm
      muscle during bulb squeezing in an exercise protocol. Normalised power output,
      expressed as percentage maximal voluntary contraction (Y, in %MVC), was related
      to the energy force of ATP hydrolysis (X = ln [ATP]/[ADP][Pi]). This relationship
      provides an in vivo measure of efficiency of oxidative work performance of
      skeletal muscle. RESULTS: During all workloads (but not at rest) intracellular pH
      was higher in the patients with cystic fibrosis than in the controls. The linear
      least square fit for Y = a-bX showed high correlations in both groups; the slope
      b was 19% lower in the patients than in the controls (11.8% v 14.5% MVC/ln M; 95%
      confidence interval for difference 0.3 to 5.0). CONCLUSIONS: In patients with
      cystic fibrosis oxidative work performance of skeletal muscle is reduced. This
      may be related to secondary pathophysiological changes in skeletal muscle in
      cystic fibrosis.

PMID- 8539681
TI  - Enhanced migration of fibroblasts derived from lungs with fibrotic lesions.
AB  - BACKGROUND: The migration and proliferation of fibroblasts may be important in
      the pathogenesis of pulmonary fibrosis. Considerable data are available on the
      proliferation of fibroblasts, but very few on their migration. METHODS: The
      migratory activity of fibroblasts obtained from lung biopsy specimens from 11
      patients with idiopathic pulmonary fibrosis (IPF) was studied using a 96-well
      chemotaxis chamber. Fibroblasts from eight normal controls, seven patients with
      interstitial fibrosis associated with a collagen vascular disease (IP-CVD), and
      13 patients with sarcoidosis were also examined. Migratory activity was tested in
      a serum-free medium in the presence and absence of platelet derived growth factor
      (PDGF), 30 ng/ml, as a chemoattractant. RESULTS: Migration of fibroblasts from
      patients with IPF was enhanced in serum-free maintenance medium alone (mean (SD)
      controls v IPF: 183 (86) v 689 (491) cells/field), and was also enhanced when
      cells were stimulated by PDGF (controls v IPF: 829 (222) v 1928 (600)
      cells/field). Fibroblasts from tissues with dense fibrosis had a greater capacity
      for migration than those from an earlier stage of fibrosis. No correlation was
      found between migratory activity and proliferative capacity of the individual
      cells. CONCLUSIONS: The fact that fibroblasts from fibrotic lungs migrate faster
      than those from controls suggests that migration is related to the initiation of
      the pulmonary fibrotic process. These in vitro studies suggest that fibroblasts
      derived from the lungs of patients with pulmonary fibrosis have a migratory
      phenotype. Such a change in fibroblast phenotype, if it occurred in vivo, may be
      important in the context of the pathogenesis of pulmonary fibrosis.

PMID- 8539682
TI  - Lung injury in patients following thoracotomy.
AB  - BACKGROUND: Postoperative lung injury is a recognised complication of thoracotomy
      for which there are few data regarding incidence and outcome. METHODS: In a case
      controlled study the notes of all adult patients who developed acute lung injury
      (ALI) or acute respiratory distress syndrome (ARDS) following thoracotomy between
      1991 and 1994 were examined and classified according to the guidelines of the
      American Thoracic Society/European Respiratory Society for ALI/ARDS. The
      predictive value of a routine preoperative assessment and duration of anaesthesia
      in determining those patients most likely to develop ALI/ARDS was assessed.
      RESULTS: Between 1991 and 1994 231 lobectomies, 103 pneumonectomies, and 135
      wedge resections and segmentectomies were performed. The overall incidence of
      lung injury was 5.1%; 17 patients developed ARDS (two survived) and seven
      developed ALI (five survived). There was no significant difference compared with
      case matched controls in preoperative spirometric values, arterial oxygen tension
      (PaO2), or duration of anaesthesia. None of these parameters was useful in
      predicting those patients most likely to develop lung injury. CONCLUSION: Lung
      injury after thoracotomy is associated with a high mortality. Conventional
      parameters for preoperative assessment do not predict those patients most likely
      to develop ALI/ARDS in these circumstances.

PMID- 8539683
TI  - Trends in the prevalence of asthma in Scottish and English primary school
      children 1982-92.
AB  - BACKGROUND: Some doubts exist as to whether the increase in the prevalence of
      asthma is real or an artefact. The 10 year trend of asthma up to 1993 in England
      and Scotland was therefore assessed. METHODS: Information on asthma and
      bronchitis attacks, occasional wheeze, and persistent wheeze in the last 12
      months, was obtained using a self administered questionnaire completed by the
      parents. Exactly the same questions were asked in 14 study areas in Scotland and
      22 study areas in England in 1982 or 1983 and in 1992 or 1993 in 5-11 year old
      children. RESULTS: The numbers of children with data for all respiratory illness
      were 5556 (85.2%) and 5801 (87.1%) in England and 3748 (90.4%) and 3738 (90.4%)
      in Scotland in 1982 and 1992, respectively. There was a significant increase in
      asthma attacks (approximately three times more in 1992 than in 1982) and
      occasional wheeze (30-60% more in 1992 than in 1982) in both sexes in England and
      Scotland. Persistent wheeze also increased in both countries, but the increase
      was significant only in England (30-40% more in 1992 than in 1982). CONCLUSIONS:
      The study coincides with others that suggest that the increased prevalence of
      asthma may be due, in part, to changes in diagnostic behaviour. However, the
      continuing increase of persistent wheeze in the total sample suggests that part
      of the increase is real. There was no difference in the increase of persistent
      wheeze between Scotland and England, but the trend was only significant in
      England.

PMID- 8539684
TI  - Self assessment of daytime sleepiness: patient versus partner.
AB  - BACKGROUND: Patients with the sleep apnoea/hypopnoea syndrome (SAHS) and their
      spouses often differ in their assessment of the patient's sleepiness. A study was
      therefore undertaken to investigate whether either the patient's or partner's
      rating on the Epworth sleepiness scale (ESS) was better related to illness
      severity. METHODS: Nocturnal variables (apnoeas+hypopnoeas/hour (AHI) and
      arousals/hour) and patient and partner ESS scores were compared in 103 new
      patients attending the sleep clinic. RESULTS: Mean patient and partner ESS scores
      were not different. In the whole population neither patient nor partner ESS
      variables correlated with AHI or arousal frequency. In the patients with SAHS
      (AHI > or = 15), partner ESS correlated weakly with AHI, but patient ESS did not.
      CONCLUSIONS: This study suggests that neither patient nor partner ESS ratings are
      strong predictors of SAHS severity.

PMID- 8539685
TI  - Attitudes of Asian medical students towards smoking.
AB  - BACKGROUND: There have been numerous studies on smoking habits among young adults
      in developed countries. Similar data from developing countries are scanty.
      METHODS: A survey of medical students from one of the medical colleges in
      Pakistan assessed their smoking habits and attitudes towards smoking. In June
      1993 a coded survey questionnaire was sent to each medical student at The Aga
      Khan Medical University in Karachi requesting data on their smoking habits, their
      attitudes towards smoking in various areas of the hospital, and their views about
      passive smoking and tobacco publicity. RESULTS: Of 324 medical students, 89%
      responded of whom 11% were current smokers. The incidence of smoking was greater
      among male students than females (17% versus 4%). The average age of initiation
      of smoking was 17 years and the major influence was friends. There was an
      increased awareness of harmful effects of smoking among medical students. Almost
      all felt that passive smoking was injurious to health. CONCLUSION: The prevalence
      of current smokers among Asian medical students was found to be 11%. Females
      smoked less than their male counterparts. There has been an increased awareness
      of the hazards of passive smoking among the medical students and most were in
      favour of legislative actions to discourage tobacco advertising.

PMID- 8539687
TI  - [Hospitals as battle fields].

PMID- 8539688
TI  - [When happiness of marriage depends on epidemiologic knowledge].

PMID- 8539689
TI  - [Organized mammography screening--a test project in 4 Norwegian counties].

PMID- 8539690
TI  - [How to make quality assurance of the meeting between two people?].

PMID- 8539686
TI  - Sleep-related breathing disorders. 4. Consequences of sleep disordered breathing.

PMID- 8539691
TI  - [Standardized patients in general practice--a new method for quality assurance in
      Noway].
AB  - Standardized patients were sent to general practitioners who use the patient list
      system in Trondheim in order to register daily clinical practice without the
      patient being unmasked. The authors explain what a standardized patient is, how
      they are taught to present a disease, and how they report on the consultation in
      a valid and reliable way. They also describe how the standardized patients were
      introduced into the doctors' patient list system. The doctors were informed about
      the project in advance. Twenty-three doctors were visited twice and one doctor
      was visited once by a standardized patient. At two of the visits the patient was
      unmasked. The conclusion is that the use of standardized patients is a valid,
      reliable and practical method for quality assurance in general practice in
      Norway.

PMID- 8539692
TI  - [Better consultations with patients' help--a method for quality assurance in
      general practice].
AB  - The authors have developed an instrument which is intended to improve
      consultations in general practice through feedback from patients. The instrument
      consists of a set of questionnaires with identical questions to patient and
      physician regarding a recently accomplished consultation. The physician is also
      asked to fill in a summary evaluation form. The emphasis is placed on the issue
      of communication between patient and physician. The answers to these
      questionnaires are used to identify areas where the physician could improve
      future consultations. Experience has shown that the instrument is easy to use,
      and provides valuable knowledge. It can be used by physicians working in a one
      physician practice or group practice. The benefit will be greatest if the
      physicians cooperate with colleagues.

PMID- 8539693
TI  - [Use and yield of microbiological diagnosis of sexually transmitted Chlamydia
      trachomatis infections in Vestfold 1984-93].
AB  - Testing for Chlamydia trachomatis has become widely available in Norway during
      the last ten years. We have evaluated the number and yield of tests in Vestfold
      county. The number of performed tests increased from 0.6 per 100 inhabitants in
      1984 to 6.5 in 1993, while the yield declined from 14.7% to 3.4%. The incidence
      of diagnosed infection declined from 4.0 per 1,000 person-years in 1988 to 2.2 in
      1993. In 1991, 59.6% of the samples were taken from women aged 15 to 29 years.
      Male patients provided 7.1% of the samples. Between 40 and 50 tests were
      performed among every 100 Vestfold women in their twenties. More than three
      quarters of the positive tests were found in women under 25 years of age or in
      men. Women 30 years of age or older accounted for 32.4% of the tests, but only
      9.3% of the positive tests; reaching a yield of less than 1.1%. We recommend that
      doctors perform fewer screening tests in women older than 25 years and more tests
      in men following notification by partner. This will increase the yield and reduce
      the number of false positive tests.

PMID- 8539694
TI  - [Routines for infection testing and vaccination against hepatitis B among
      applicants for asylum. A questionnaire study among health personnel responsible
      for reception of asylum applicants].
AB  - The authors performed a questionnaire survey to investigate the current routines
      for screening applicants for asylum for hepatitis B virus, HIV and intestinal
      parasites, and for vaccination against hepatitis B. The response rate was 82% (n
      = 80). Of the respondents, 58% were physicians, 23% public health nurses and 18%
      nurses. Without regard to country of origin of the applicant 71% of the health
      personnel usually offer an HIV-test and 77% an HBsAg-test. Few differentiated
      their testing routines according to country of origin. Many agreed that an HIV
      test (49%) and an HBsAg-test (65%) ought to be made compulsory. 26% usually offer
      vaccination against hepatitis B, while 54% do so if the person concerned is an
      infant. Routine screening for intestinal parasites was reported by 27% of the
      health personnel, but more than half (54%) take only one sample from each
      patient. Health control of applicants for asylum provides a good opportunity to
      give information about the transmission of hepatitis B and HIV, preventive
      measures, and testing.

PMID- 8539695
TI  - [Increased incidence of severe Streptococcus group A infections in Noway during
      the last 10 years. New outbreak 1993-94].
AB  - The article summarizes the epidemiology of disease caused by Streptococcus
      pyogenes in Norway during the last two decades, with emphasis on trends since the
      late 1980s. The description is based on the National Notification System for
      Infectious Diseases, and on microbiological data. The nationwide outbreak in 1987
      88, caused mainly by M-1 organisms, was followed by several years with remarkably
      low incidences of invasive disease. However, since late in 1992 there has again
      been a nationwide outbreak that reached even higher numbers of invasive cases
      than the one in 1988. While 106 cases of systemic group A streptococcal disease
      were recorded in 1988, the numbers for 1993 and 1994 were 143 and 188
      respectively (population 4.3 million). No change has taken place in the
      laboratory-based notification system that could explain the observed phenomena.
      Previously seldom observed clinical manifestations, such as fulminant
      septicaemia, necrotising fasciitis and pneumonia with empyema, were again
      recorded; as during the 1988 outbreak.

PMID- 8539696
TI  - [Transmissible spongiform encephalopathies--an unconventional contagious agent].
AB  - The clinical appearance, pathogenesis and epidemiology of the most important
      human and animal spongiform encephalopathies is reviewed. These comprise a
      heterogenous group of diseases with both transmissible and hereditary elements in
      their etiology. They are characterized by neurodegenerative changes in complete
      absence of inflammatory and immunological reaction. After a long incubation time
      there is a progressive development which usually leads to death. The most usual
      symptoms are motoric disturbances, coordination problems and mental retardation.
      The transmissible agent involved is unconventional, probably a modified host
      protein, called prion. Post-translational alterations of the prion protein seem
      to be of key importance in the development of pathogenic properties. The
      mechanism of replication and transmission of prions is not clear.

PMID- 8539697
TI  - [Indications for testing for sexually transmitted Chlamydia trachomatis
      infections].
AB  - Laboratory testing for sexually transmitted Chlamydia trachomatis infection is
      widely used in Norwegian general practice. The yield of this testing is
      declining, since the prevalence of infection in the community has decreased.
      Thus, the cost-effectiveness of testing is reduced, and the risk of false
      positive results using non-culture methods has increased. In cooperation with a
      panel of medical microbiologists, gynaecologists, venerologists, general
      practitioners and public health specialists, we have reviewed the literature and
      drawn up a set of recommendations for the use of laboratory testing for genital
      C. trachomatis infection. We emphasize clinical testing of men and women,
      notification of partners in order to reach males, and screening of women under
      the age of 25 after each change of sexual partner.

PMID- 8539698
TI  - [False positive tests of sexually transmitted Chlamydia trachomatis infections].
AB  - We describe the cases of three women who, in 1994, filed complaints of alleged
      false-positive diagnosis of Chlamydia infection with the Norwegian Patients'
      Association. They were living in mutually monogamous relationships, but had
      genital symptoms when they visited their doctor. The positive tests had adverse
      psychological and social consequences. Two women and their partners had negative
      repeat tests elsewhere, while one woman found that the laboratory, but not her
      doctor, had registered her primary test as negative. We suggest measures to
      reduce the number of false-positive tests and to prevent adverse psychological
      and social consequences of such tests. Patients should be involved in the
      decision to perform a Chlamydia test. The doctors should be aware of the
      possibility of false results, and must improve their information to patients with
      positive tests.

PMID- 8539699
TI  - [Scientific misconduct and medical research in Norway].
AB  - To evaluate the occurrence of scientific misconduct in medical research in
      Norway, 274 randomly selected Norwegian scientists were asked to complete a
      questionnaire on their knowledge and experience of deviations from the Medical
      Research Council's professional standard. Altogether 215 (80%) completed the
      questionnaire. Knowledge of severe misconduct was reported by 22% while 3%
      reported occurrence of falsification or fabrication of data within their own
      research group. Ten percent of the respondents knew of plagiarism, while 58%
      confirmed experience of less severe misconduct, most frequently misleading
      authorship. Nine percent had themselves contributed to one or more incidents of
      misconduct. Occurrence of misconduct was not related to area of research. The gap
      between admitting own misconduct and knowledge of misconduct by others was
      striking. According to 54% of the respondents, organized ethical education for
      young scientists would be an effective way of preventing misconduct. Altogether,
      the present data show that efforts are needed to prevent misconduct in medical
      research.

PMID- 8539700
TI  - [the Liland case. The medical-legal declarations].
AB  - On the basis of new medico-legal experts' opinions the Norwegian High Court
      decided in the Liland case that the original medico-legal experts had been
      mistaken. The prosecution wanted the High Court to hear the experts, but this
      request was rejected. The High Court's decision led to acquittal of Liland who
      had been convicted 24 years earlier of a double murder. With the support of seven
      British and two German forensic pathologists it is maintained that the original
      experts were right. This does not mean that a standpoint has been taken as to who
      could have committed the crime.

PMID- 8539701
TI  - [Conflicts in connection with leadership of medical laboratories].

PMID- 8539703
TI  - [Alcohol consumption among adolescents in 3 municipalities].

PMID- 8539702
TI  - [Alcohol abusers after treatment at clinics--a follow-up study].

PMID- 8539704
TI  - [3 independent observations].

PMID- 8539705
TI  - [Literature lists--authorship].

PMID- 8539706
TI  - [The rise and fall of permanently employed physicians in primary health care
      (1970-2000)].

PMID- 8539707
TI  - [Are lecturers for the courses of the Medical Society not wanted?].

PMID- 8539708
TI  - [Hospitals misuse employments of trainee physicians].

PMID- 8539709
TI  - [Tumor cells in peripheral blood and bone marrow in patients with prostatic
      cancer. Many unanswered questions].

PMID- 8539710
TI  - [Computer tomography for spinal puncture in suspected purulent meningitis?].

PMID- 8539711
TI  - [Hyperlipidemia, coronary disease and antilipemic drugs--do they help?].

PMID- 8539712
TI  - [New therapeutic methods for tachycardia].

PMID- 8539713
TI  - [Radiofrequency ablation of heart arrhythmias. Results in the first 150 patients
      treated at the Arrhythmia center in Oslo].
AB  - The authors review the first 150 patients with cardiac arrhythmias who were
      treated with radio-frequency ablation at a Norwegian arrhythmia centre. The
      clinical success rate (either electrophysiological cure or a dramatic reduction
      in the severity and frequency of the attacks) was 97%. 11 patients were treated
      for two or more arrhythmias. In 27 patients two, occasionally three, sessions
      were required to obtain a satisfactory clinical result. Repeat ablation is
      scheduled for three cases where the treatment was unsuccessful. Among 190
      ablations, 13 complications occurred, none of which resulted in permanent
      sequelae. The time spent on each procedure, and particularly the long time spent
      on fluoroscopy during the earlier procedures, demonstrates the existence of a
      learning curve for ablation. This lends support to the authorities' restriction
      of treatment of arrhythmias by ablation to only two laboratories in a population
      of four million.

PMID- 8539714
TI  - [Prostate-specific membrane antigen. A new sensitive molecular indicator in
      metastasizing prostatic cancer].
AB  - Prostate cancer is the most common malignant disease in men in western societies.
      Extracapsular spread of carcinoma is found in approximately half of the patients
      that are treated by radical prostatectomy. Recently, a new prostate-specific
      membrane glycoprotein was cloned and sequenced. A highly sensitive and specific
      nested reverse transcriptase polymerase chain reaction has been developed to
      detect early occult haematogeneous micrometastatic prostate cells. We analysed
      venous samples from 17 patients with metastatic prostate cancer using a modified
      reaction assay. This showed presence of micrometastatic prostate cells in 14
      patients. Molecular detection of circulating prostatic epithelial cells could
      improve clinical staging and treatment of early prostate cancer.

PMID- 8539715
TI  - [Adult-onset Still's disease. An underdiagnosed condition?].
AB  - Adult onset Still's disease is a variant of systemic juvenile chronic arthritis
      in adulthood. The clinical picture is characterized by high spiking fever,
      arthralgia/arthritis, transient erythema, acute-phase reaction including elevated
      ESR, CRP and neutrophilia, resembling acute bacterial infections.
      Hyperferritinaemia and hepatic dysfunction are usually present, and the patients
      frequently have a sore throat. Extraarticular features, such as splenomegalia,
      serositis and pericarditis may be parts of this disease as well. Two cases are
      described, who were admitted to the Department of Internal Medicine of a small
      Norwegian hospital. Both patients were subjected to exhaustive and laborious
      investigations for the purpose of disclosing malignancy and/or septicaemia.
      Following adequate glucocorticoid therapy, both were asymptomatic after less than
      a week's treatment and after five months' follow-up. Two sets of diagnostic
      criteria are presented, having different sensitivity, although almost equal
      specificity. Still's disease in the adult may be an underdiagnosed clinical
      entity, but should definitely be considered to be a possible differential
      diagnosis when investigating suspected malignancy, including lymphoma and febrile
      conditions suspected of septicaemia.

PMID- 8539716
TI  - [Systemic sclerosis. A rare connective tissue disease with manifestations in many
      organs].
AB  - Systemic sclerosis (scleroderma) is a rare connective tissue disease which can
      affect most human organs. Systemic sclerosis is divided into two groups: one
      diffuse scleroderma form, which is often more serious, with extensive organ
      involvement, and a limited scleroderma form with good prognosis. During a period
      of 20 years from 1974 to 1994, 14 patients were diagnosed as having systemic
      sclerosis in a population of approximately 150,000. Five were classified as
      having the diffuse form, and nine as having the limited form. Ten patients were
      found to have antinuclear antibodies. All patients had Raynaud's phenomena and
      scleroderma. Involvement of the gastrointestinal tract/lungs and joint-tendon
      sheets were found in six and eight patients respectively. Muscles, heart and
      kidneys were involved in three of the patients. Our results correspond with those
      described in the literature.

PMID- 8539718
TI  - [Arteriovenous fistula as a complication of percutaneous renal biopsy].
AB  - Arteriovenous fistulae is a well known but rarely diagnosed complication of
      percutaneous biopsy of kidney allografts. In most cases the fistula are
      clinically occult. Most of the remaining fistulas disappear spontaneously.
      However they may result in severe bleeding, uncontrollable hypertension or
      deterioration of renal function. These are features that may require correction,
      either surgically or by arteriographic embolition. Between 1991 and 1994
      arteriovenous fistulas were identified in two patients who had undergone
      percutaneous renal biopsy. In our cases the fistulas never became clinically
      significant.

PMID- 8539717
TI  - [Acute psychosis--an unusual clinical manifestation of primary
      hyperparathyroidism].
AB  - In 1942, the Norwegian psychiatrist Eitinger drew attention to the fact that
      acute psychosis may be the presenting and major symptom of primary
      hyperparathyroidism. A case of this variety is reported. In the course of two
      months a 77-year old woman developed an acute psychosis characterized by apathy,
      amnesia, somatic delusions and hallucinations. Initially, the case was
      misinterpreted as senile dementia. The serum calcium level was 4.3 mmol/l. After
      parathyroidectomy her mental symptoms were completely relieved.

PMID- 8539719
TI  - [Omentoplasty in bronchopleural fistulas after pneumonectomy].
AB  - A bronchopleural fistula after pneumonectomy is a serious complication, and
      successful healing is a therapeutic challenge. Increasing evidence indicates that
      closing of the fistula combined with wrapping the bronchus with omentum
      (omentoplasty) can secure permanent healing in the majority of cases. The omentum
      is highly vascularized, and has angiogenetic and anti-inflammatory properties. We
      describe two patients with bronchopleural fistulas after surgery for lung cancer.
      The fistulas were diagnosed respectively one and fifteen months after operation.
      Both were treated successfully with antibiotics, surgical debridement, secondary
      closure and wrapping of the fistulas with omentum transposed from the abdomen
      with its attachment to the right gastroepiploic artery preserved.

PMID- 8539720
TI  - [Treatment of hyperlipidemia. Guidelines for treatment of hyperlipidemia for
      secondary prevention of ischemic heart disease].
AB  - The new programme and guidelines have been developed for secondary prevention of
      coronary heart disease in patients with hyperlipaemia. All patients who have
      suffered myocardial infarction, have angina pectoris, have had a coronary by
      pass, or have undergone angioplastic surgery, should have the following serum
      lipid profile established within one to two months: total cholesterol < 5 mmol/l,
      ratio total cholesterol/HDL-cholesterol < 4, LDL-cholesterol < 3 mmol/l,
      triglycerides < 2 mmol/l and HDL-cholesterol > 1 mmol/l in men and 1.3 mmol/l in
      women.

PMID- 8539721
TI  - [Spinal puncture in suspected purulent meningitis].
AB  - Today, CT scan of the brain is performed as a routine a the first diagnostic
      procedure in cases of suspected acute subarachnoid haemorrhage. Subarachnoid
      blood is demonstrated in a high percent of these cases provided that the scan is
      carried out within the first few days after the bleeding. Furthermore, the scan
      may also disclose localised intracranial haematoma or other expansive lesions
      with brain shift. In such cases, lumbar puncture may be dangerous, due to the
      risk of herniation. In cases of suspected acute bacterial meningitis or other
      infectious disease of the central nervous system, performance of a CT scan before
      lumbar puncture is not a well established procedure. Two case histories are
      described. Both patients had brain abscesses and deteriorated dramatically after
      lumbar puncture. The role of brain CT scanning in the management of such patients
      is discussed.

PMID- 8539722
TI  - [Reduction in prescription of B-preparations in general practice].
AB  - In order to evaluate the effect of a collective agreement on change in GP's
      prescribing habits with regard to benzodiazepines and analgetics containing
      codeine, the prescriptions, measured in DDD, for the period September - November
      1993 were compared with the prescriptions issued during the same period in 1994.
      All 11 general practitioners in three neighboring municipalities around the small
      town of Roros took part in the project. Co-operation with the only pharmacy in
      the region was established. In 1993, baseline consumption of the actual drugs was
      slightly below the average for Norway. A total decline of approximately 50% in
      prescribed DDD was obtained, with a reduction in prescriptions for hypnotics,
      anxiolytics and analgetics alike.

PMID- 8539724
TI  - [Health and work conditions of physicians. Experiences and visions 35 years after
      certification].

PMID- 8539723
TI  - [Long-term psychiatric patients in a sector of Oslo].
AB  - A prevalence of 6.9/1000 for long term psychiatric patients was found in an Oslo
      catchment area by sending a questionnaire to practising physicians and medical
      and social agencies. The respondents were asked to state the diagnoses. This
      produced prevalences of 2.6 for schizophrenia, 1.1 for affective psychoses and
      0.8 for paranoid psychoses. The majority of the subjects were served primarily by
      the outpatient clinic and only a small minority by inpatient units. The primary
      health care and social care institutions were inadequately involved and
      coordinated. Less than 50% of the subjects obtained sufficient service in spite
      of an average of 2.1 treatment contacts. It is of interest to note that the
      larger the number of contacts, the more the service was found to be inadequate.

PMID- 8539725
TI  - [Structural changes of health care in Germany].

PMID- 8539726
TI  - [Who should perform abortion counseling?].

PMID- 8539728
TI  - [Who should perform abortion counseling?].

PMID- 8539727
TI  - [Who should perform abortion counseling?].

PMID- 8539729
TI  - [Indications for testing of sexually transmitted Chlamydia trachomatis
      infections].

PMID- 8539730
TI  - [About co-authors and pathologists].

PMID- 8539732
TI  - [Mandatory information and cheaper drugs].

PMID- 8539731
TI  - [Prescription drugs against osteoporosis].

PMID- 8539733
TI  - [1995 Nobel Prize in physiology and medicine. The mystery of fetal development].

PMID- 8539734
TI  - [Caffeine--the gentle addictive stimulant].

PMID- 8539735
TI  - [Finding winter horrible...].

PMID- 8539736
TI  - [Is health education actually beneficial?].

PMID- 8539737
TI  - [Development of risk factors for cardiovascular diseases among persons aged 40-42
      years in the county of Finnmark 1973-93].
AB  - During the period 1973-1993, the National Health Screening Service carried out
      five screenings of risk factors for cardiovascular disease among 40-42 years of
      age in the county of Finnmark. Risk for myocardial infarction has decreased,
      mainly due to reductions in total cholesterol, which fell by more than 10% in
      both sexes from 1973-74 to 1993. Cholesterol levels now seem to be stabilizing.
      Considerably fewer persons smoked daily in 1977-78 than in 1973-74. From 1977-78
      to 1993, little change occurred among men, but the percentage of women who smoked
      daily increased by 10%. Systolic and diastolic blood pressure were slightly
      higher in 1993 than in 1990. Since 1987-88 consumption of butter and of
      traditionally made coffee (boiled, not filtered) has decreased. Compared with
      other counties, Finnmark shows high values for cholesterol, smoking habits and
      "boiled" coffee. Preventive measures still have a potential to influence the
      future trend.

PMID- 8539738
TI  - [Cornelia de Lange syndrome and the woman behind the syndrome].
AB  - The phrase syndrome indicates that certain symptoms and signs run together as a
      clinical entity. Collectively they characterize a particular disease or abnormal
      condition. Some syndromes are rare, but it is important to recognize them.
      Correct and early diagnosis is important for the individuals concerned, and for
      their families. Cornelia de Lange syndrome in its classical form is a syndrome of
      several congenital abnormalities and mental retardation. When not fully developed
      the syndrome may cause diagnostic problems. The authors discuss some biographical
      data about Cornelia de Lange and some matters concerning the syndrome.

PMID- 8539739
TI  - [Cocaine abuse and acute heart disease].
AB  - Cocaine abuse is an increasing problem in western societies, and health personnel
      should be aware of the cardiovascular effects of cocaine, of which myocardial
      infarction is the most frequent reported complication. Cardiac arrhythmia is
      another serious complication. We describe a young female who, after injecting
      cocaine intravenously, suffered from circulatory collapse, thought to represent
      an arrhythmia. The authors discuss the pharmacological and clinical aspects of
      cocaine-induced myocardial infarction and arrhythmias, and suggest guidelines for
      treatment.

PMID- 8539740
TI  - [Reactions to food].
AB  - Adverse reactions to food occur in about 1-2% of the population, but are reported
      more frequently by patients. Most reactions to food are not caused by allergy.
      IgE-mediated food reactions are well known and of major clinical significance
      owing to their potentially dangerous, even life-threatening character. Adverse
      reactions to food can also be caused by immunological mechanisms other than IgE
      mediated reactions such as, enzyme deficiencies, active pharmacological
      substances in food and psychological mechanisms. Double-blind provocation is the
      only way to diagnose a positive reaction to a food item with some certainty.
      Regretably no objective measures for food reactions exist.

PMID- 8539741
TI  - [Henrik Wergeland's disease and death. 150th anniversary].
AB  - It is 150 years since the Norwegian poet Henrik Wergeland (1808-45) died. It is
      commonly assumed that the suffered from "phthisis" or--as we now call it-
      tuberculosis. This paper discusses the symptoms mentioned in Wergeland's own
      letters, which seem to indicate that the diagnosis was instead pulmonary cancer.

PMID- 8539742
TI  - [Johan Sebastian Welhaven's parkinsonism. An insight into the history of
      literature].
AB  - The article is meant to give new insight into the history of literature: During
      the last ten years of his life, Welhaven produced neither poetry nor prose and
      lived withdrawn in his own house, mainly because he had Parkinson's disease. He
      understood himself, as his doctors did--and his biographers--that he suffered
      from a brain disease. However, nobody was able to make a Parkinson diagnosis in
      Norway in the 1860s. This was perhaps possible for a handful of French
      neurologists, who at this time "rediscovered" James Parkinson's "An Essay on the
      shaking palsy" from 1817--and named the disease Maladie de Parkinson, or
      Parkinson's disease. When a neurologist today reads Welhaven's own observations
      or those of his contemporaries, and his biographies, he has little doubt about
      the diagnosis.

PMID- 8539743
TI  - [Medical treatment abroad. Why Bjornstjerne Bjornson died in Paris 1910].
AB  - The Norwegian poet and playwright Bjornstjerne Bjornson (1832-1910), Nobel prize
      laureate in literature 1903, died in Paris. He had suffered from angina pectoris
      for a few years and had difficulties in walking because of thrombophlebitis in
      his right leg. In 1909, he had received electrotherapy from a French
      physiologist, Dr. d'Arsonval, in Paris and felt rejuvenated after the treatment.
      In May 1909, while undergoing spa treatment in Larvik, he had an apoplexy which
      left him with a left hemiparesis, presumably due to a thrombosis of the right
      internal carotid artery. He became bedridden, developed focal epilepsy and was
      unable to participate in the national cultural activities that used to be part of
      his life. He then decided to return to Paris for another series of
      electrotherapy. He was brought to Paris in the Royal Danish railway carriage, and
      was received at the border as an official guest of the French republic. The
      electrotherapy machine was installed in his room at Hotel Wagram, where he stayed
      for several months while receiving treatment. However, his health deteriorated
      during the treatment and he died in Paris in April 1910.

PMID- 8539744
TI  - [Circumstances surrounding the discovery of Rontgen rays].
AB  - The 8th of November marks the centennial of the discovery of Rontgen rays. This
      discovery occurred serendipitously during an experiment with cathode rays by the
      physicist Wilhelm Conrad Rontgen in Wurzburg, Germany. Not many other discoveries
      in basic natural science have had such an enormous impact and immediate
      application in medicine. Rontgen had a Dutch connection, since he spent 17 years
      of his childhood and youth in the Netherlands. In his final school report, the
      only subject in which the later Nobel prize winner in physics received poor marks
      was physics! Notes released 70 years after Rontgen received his prize revealed
      that the Nobel Committee for Physics actually had recommended that the prize be
      divided equally between Rontgen and Philipp Lenard, another eminent German
      physicist.

PMID- 8539745
TI  - [100 years of medical radiology--development in Norway].

PMID- 8539746
TI  - [Academic degrees and changing ceremonies].
AB  - The traditions and ceremonies regarding doctoral dissertations in Europe date
      back to early medieval times, to the school of health at Salerno. The University
      of Oslo, founded in 1811, inherited the traditions from Denmark. Up to 1845, the
      dissertations were held in Latin, which was a burden on the candidates. The first
      four candidates who presented a thesis for a doctorate were all from the Faculty
      of Medicine. After 1845, the Norwegian language was permitted, but up to the end
      of the century there were still only few dissertations, and a doctorate degree
      was not highly valued. The number has since increased, and this degree is more
      highly esteemed. The ceremonies around the dissertations have also changed. The
      first promotions included solemn procedures in Latin, but later on the promotion
      ceremonies disappeared for 91 years. Promotion ceremonies reappeared in 1933, but
      changes have been observed more recently, probably related to changing cultural
      opinions and trends. The policy today seems to indicate a trend towards more
      ceremony, accompanied by festivity.

PMID- 8539747
TI  - [Publicly employed physicians--war years and post-war judicial process].
AB  - During the Second World War, publicly employed medical officers in Norway were
      given a role which disharmonized in many ways with the role they had before 9
      April 1940. They had been employed on terms which included loyalty towards
      employer, colleagues and patients. After the outbreak of the war and for five
      years to come, loyalties were put to the test. At the same time their actual
      services became more demanding. Their daily work was complicated by various laws
      and regulations, and the political situation in general hindered personal and
      professional development and free communication between doctors and patients, and
      between colleagues. After the war the central medical administration was
      relentless and the sanctions against those who had supported the occupying powers
      were exceptionally hard. The author emphasizes the doctors' personal experiences
      during the war and the first postwar years. The most important sources are
      personal testimonies, as they come forth in public records, biographies and
      interviews.

PMID- 8539748
TI  - [The 50th anniversary--seen from the other side. A German colleague's impressions
      from his years in Norway as a military surgeon during 1940-45].

PMID- 8539749
TI  - [The Pickwick syndrome. From literary speculations to sleep research].
AB  - The "wonderfully fat boy" Joe described in The Pickwick Papers, by Charles
      Dickens, is remarkable for his glorious appetite and many attacks of sleep during
      the day. His medical condition was introduced as the Pickwick syndrome by Burwell
      et al. in 1956. For some 20 years this was an important stimulus for sleep
      research. Some literary and historical aspects of The Pickwick Papers are
      presented. The many diagnoses given to poor Joe are discussed. This diagnostic
      survey may still be of interest, even if the syndrome has virtually disappeared
      from medical literature. How does the Pickwick syndrome, as doctors today see it,
      fit Dickens' original description? Did Joe really suffer from the Pickwick
      syndrome?

PMID- 8539750
TI  - [In search of medicine in literature. An introduction to the field of literature
      and medicine].
AB  - In the last two decades increasing academic interest has been shown for the field
      of literature and medicine. This article introduces the field, and outlines
      different approaches. Teaching literature in medical education may help
      physicians and medical students to develop skills and insight of importance for
      good understanding and practice of their profession. Literary theories may
      contribute to the understanding of medical practice.

PMID- 8539751
TI  - [About physicians as characters in Norwegian literature].
AB  - A journey has been made through Norwegian literature of the last century for the
      purpose of presenting to the readers of this journal what is to be found of
      literature describing doctors. The purpose was also to find literary
      interpretations of the historical evolution of the doctor's role. A
      characteristic common to all the doctors in the study is that they all suffer
      from various personal problems such as neuroses, drug abuse, overindulgence in
      alcohol, family problems, loneliness, maltreatment of children, suicide or
      murder. A closer study of the description of six local doctors shows small
      changes in work structure and social relations during the century, but more
      popular behaviour is found in the portrayal of more modern characters. Good and
      rich portraits of doctors in Norwegian literature are rare. Those that are found
      have been created to describe personal or social problems rather than to tell
      especially what it is like to be a doctor.

PMID- 8539752
TI  - [Mikhail Bulgakov--a colleague and cult figure].
AB  - Mikhail Bulgakov (1891-1940) was medically qualified, but practised as a doctor
      only a few years before he launched on a full time career as a writer. His
      writings are marked by exuberant satire and burlesque phantasy, a genre condemned
      anti-Sovietic. Throughout his writing life, Bulgakov found it extremely difficult
      to get his writings published. He did not become known to the reading public
      inside and outside USSR until 30 years after his death.

PMID- 8539753
TI  - [Health service for physicians. What do physicians want--form and substance?].
AB  - In 1991, a special health service for doctors was started in Rogaland county.
      Three years later this service was evaluated via a questionnaire. Two thirds of
      109 doctors were very satisfied, and only one was dissatisfied with this health
      service. The results show a need for both psychosocial and somatic health
      examinations for doctors.

PMID- 8539754
TI  - [Physician's role in Norwegian art of painting].
AB  - The author reviews paintings of doctors by Norwegian artists. Many interesting
      pictures have been painted, especially during the era of naturalism at the end of
      the last century. The artist and journalist Christian Krohg contributed to an
      early discussion of the role of the doctors in connection with social problems in
      Norway. In the 1930s, Finn Faaborg illustrated the relation between doctor and
      patient in the case of tuberculosis, and Carl von Hanno revived the problem of
      prostitution. Bendik Riis, himself a psychiatric patient, with his huge painting
      Castraktion, shows his fear of castration and lobotomy, and also his opinion of
      the health authorities' lack of respect for the patient. Norwegian painters have
      obviously contributed to a fruitful discussion of the role of the doctor in
      society.

PMID- 8539755
TI  - [German medicine during the Nazi regime--cooperation and resistance].
AB  - The author reviews the collaboration between the medical profession and the Nazis
      in Germany during the period 1933-45, based mainly on recent literature. As
      several authors have pointed out, the medical profession became extensively
      involved in the implementation of a sterilisation programme, the practice of the
      racial laws, the exclusion of Jews from the medical practice, the Euthanasia
      Programme and the performance of painful and dangerous experiments on prisoners.
      Although the resistance to Nazism was weak and did not succeed in preventing the
      atrocities, it deserves historical attention. The resistance seems to have been
      motivated by an alternative ideology, such as Socialism, Christianity and
      Humanism. There were also some protests based on principles of medical ethics.
      Passive neutrality through "internal exile" seemed to have been difficult, and
      heroic resistance was rare, but did occur.

PMID- 8539756
TI  - [The normal and the pathological].
AB  - The main problem of modern health care is to express its goals and its limits. To
      do this it is necessary to answer the fundamental question: what is normal and
      what is pathological? The French physician and philosopher Georges Canguilhem has
      tried to answer this question. He claims that for medicine, the difference
      between these fundamentals is determined by normativity and not by science. In
      doing this he wishes to save the autonomy of the individual patient and to
      delimit medicine from science.

PMID- 8539757
TI  - [Planning of a museum of medical history--thoughts about why and how].
AB  - Plans are being made for a new, national museum of medical history. The need for
      a central institution to take care of the dimension of time in the development of
      medical and health science has become more and more obvious in recent years. A
      new museum should meet the visitors by means of modern exhibition and teaching
      techniques, but should also serve as a center of competence for historical
      research on health-related topics. The building of a new University Hospital in
      Oslo has opened up possibilities of converting one of the old buildings into a
      museum.

PMID- 8539758
TI  - [Medicine and modernism].

PMID- 8539759
TI  - [Predictive value of Calprotect Phical].

PMID- 8539760
TI  - [More on lichen].

PMID- 8539761
TI  - [Special issue dedicated to the 90th anniversary of the day of birth of the
      academician A. A. Smorodintsev].

PMID- 8539762
TI  - [Vaccines against viral hepatitis B: results and prospects].

PMID- 8539763
TI  - [Rubella and prospects for vaccine prophylaxis of it].

PMID- 8539764
TI  - [Poliomyelitis in Europe: 1950-1951].

PMID- 8539765
TI  - [In memory of the creator of domestic virology, Academician Anatolii
      Aleksandrovich Smorodintsev].

PMID- 8539766
TI  - [Major results of the study of arbovirus infections in the Soviet Union,
      conducted under the supervision of A.A. Smorodintsev].

PMID- 8539767
TI  - [Vaccine prophylaxis of influenza].

PMID- 8539768
TI  - [The nature of pandemic strains of the influenza virus].

PMID- 8539769
TI  - [Immunoprophylaxis of childhood viral infections].

PMID- 8539770
TI  - [Immunoprophylaxis of respiratory syncytial (RS-viral) infection: results and
      prospects].

PMID- 8539771
TI  - [The creative legacy of academician of the Academy of Medical Sciences of the
      USSR, Anatolii Aleksandrovich Smorodintsev (on his 90th birthday)].

PMID- 8539772
TI  - [History of purification, attenuation and testing a measles vaccine made from the
      strain "Leningrad-16" (L-16)].

PMID- 8539773
TI  - [Basis for the need for mass revaccination against measles and results of
      conducting it].

PMID- 8539774
TI  - New cytotoxic steroids from the marine sponge Dysidea fragilis coming from the
      lagoon of Venice.
AB  - The sterol composition of the sponge Dysidea fragilis, coming from the lagoon of
      Venice, has been investigated; our results confirmed the variability of D.
      fragilis biochemistry. The sponge elaborates, in addition to eight usual 3 beta
      hydroxy sterols, thirteen polyhydroxysterols, eight of them (6-13) were novel
      compounds. Their structures were established by spectroscopic data. New compounds
      3 beta,5 alpha,6 beta,7 alpha-tetrahydroxy-cholest-8(9)-en-11-one (8), 3 beta,5
      alpha,6 alpha-trihydroxy-9,11-secocholest-7-en-9-one (9) and 3 beta,5 alpha,6
      alpha,9 alpha-tetrahydroxy-cholest-7-ene-6-sulfate (11) were proved to be
      cytotoxic on two different tumor cell lines in vitro.

PMID- 8539775
TI  - Steroid saponins from fenugreek seeds: extraction, purification, and
      pharmacological investigation on feeding behavior and plasma cholesterol.
AB  - The seeds of fenugreek (Trigonella foenum graecum L.) are traditionally assumed
      to have restorative properties. We have recently shown that a fenugreek seed
      extract containing steroid saponins increased food consumption and induced
      hypocholesterolemia in rats. This study aims to investigate the specific role of
      purified steroid saponins in these properties. For this purpose, an original
      technique for extraction and purification of steroid saponins was carried out.
      Thereafter, the effects of these steroid saponins were investigated on feeding
      behavior and metabolic endocrine changes in normal and diabetic rats. All the
      steroid saponins (furostanol type) were extracted from the seeds and separated
      from all other constituents of the entire extract by using several purification
      procedures to give an extract containing at least 90% of steroid saponins.
      Pharmcological experiments were performed in vivo in normal and streptozotocin
      diabetic rats: steroid saponins were administered chronically mixed with food
      (12.5 mg/day per 300 g body weight). Our data show that the treatment with
      steroid saponins significantly increased food intake and the motivation to eat in
      normal rats, while modifying the circadian rhythm of feeding behavior; it also
      stabilized the food consumption in diabetic rats, which resulted in a progressive
      weight gain in these animals, in contrast to untreated diabetic controls. Both in
      normal and diabetic rats, steroid saponins decreased total plasma cholesterol
      without any change in triglycerides. In conclusion, the present work reports a
      clear methodology to obtain all the steroid saponins and demonstrates that these
      saponins enhance food consumption and motivation to eat, and reduce plasma
      cholesterol levels in rats.

PMID- 8539776
TI  - Steroid sulfatase and the Y chromosome hypertensive locus of the spontaneously
      hypertensive rat.
AB  - The spontaneously hypertensive rat (SHR) has a Y chromosome locus that increases
      blood pressure. This locus requires an androgen receptor and testosterone for
      maximum expression. Steroid sulfatase (STS) catalyzes the conversion of steroid
      sulfates to their active nonconjugated form. In some mammals the steroid
      sulfatase locus (Sts) is on the Y chromosome, although the rat Sts is on the X
      chromosome. We measured STS activity levels in SHR and normotensive Wistar Kyoto
      (WKY) males. SHR had significantly higher STS activity in testes, adrenal gland,
      liver, and hypothalamus. The Km values for STS in the two strains were not
      significantly different; thus, activity differences were likely due to
      differences in enzyme amounts. STS activity was measured in the backcross strains
      SHR/y and SHR/a to test and/or confirm a Y chromosome influence on STS. STS
      activity levels in these strains were intermediate between those of SHR and WKY.
      Because the blood pressures of SHR/y and SHR/a were also intermediate between SHR
      and WKY, the STS activity could be a secondary response to the hypertension. An
      alternative hypotheses is that a regulatory locus in addition to the structural
      locus is responsible for STS activity levels, and this regulatory locus is on the
      rat Y chromosome. Further study is needed to discriminate between these
      possibilities, and until the second hypothesis can be eliminated, the Sts locus
      or its modifier loci remain a potential component of the Y chromosome
      hypertensive locus.

PMID- 8539777
TI  - Use of non-radioactive labels for half-life measurement of sex hormone-binding
      globulin in the rabbit.
AB  - The purpose of this study was to investigate two methods for labeling rabbit sex
      hormone-binding globulin (rSHBG) with non-radioactive material, biotin (B) and
      europium (Eu3+), in order to obtain stable labeled SHBG and measure in vivo its
      metabolism and distribution. The obtained half-life values were compared with
      [125I]rSHBG half-lives. rSHBG was first isolated by immunoaffinity chromatography
      using an immobilized monoclonal anti-human SHBG (hSHBG) antibody that cross
      reacts with rSHBG. This purified rSHBG was labeled by either biotin-X-N
      hydroxysuccinimide ester (rSHBG-B), Eu3(+)-diethylenetriaminepentaacetic
      dianhydride, or Eu(3+)-isothiocyanatobenzyldiethylenetriamine-tetraacetic acid
      reagents (rSHBG-Eu3+) or by 125I using Bolton and Hunter reagent ([125I]rSHBG).
      The labeling procedure preserved the main properties of native SHBG: interaction
      with the lectine concanavaline A-Sepharose, recognition by anti-hSHBG monoclonal
      antibody, and, although lower than in native SHBG, the binding affinity for 5
      alpha-dihydrotestosterone. These characteristics were the prerequisite for
      reliable measurement of the metabolism of labeled SHBG. Labeled rSHBG was
      injected into various rabbits with blood sampling at 2 min and at 1, 2, 4, 8, 12,
      24, 48, 72, and 96 h after injection. rSHBG-B or desiaylated rSHBG-B and rSHBG
      Eu3+ were captured from serum samples by tubes coated with anti-hSHBG antibody
      prior to the following detection procedure: biotin was detected by luminometry
      with the [streptavidin-alkaline phosphatase-dioxetane (AMPPD)] system and
      europium by time-resolved fluorimetry. [125I]rSHBG was detected by measurement of
      radioactivity either directly on serum or after fixation on concanavaline A
      Sepharose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8539778
TI  - Synthesis of novel intranuclear diazasteroids.
AB  - By use of the aza Diels-Alder reaction a series of aminoisoquinolines and
      aminoquinolines have been elaborated to provide an effective synthesis of diverse
      diazasteroids. In particular, representative 1,11-diaza-, 3,11-diaza-, and 4,11
      diazasteroids have been synthesized from cyclopentadiene. From dihydropyran a
      4,11-diaza-15-oxa-D-homosteroid has been obtained.

PMID- 8539780
TI  - Determination of the glucurono-conjugated position in bile alcohol glucuronides
      present in a patient with cerebrotendinous xanthomatosis.
AB  - The determination of the glucurono-conjugated position in three bile alcohol
      glucuronides secreted in bile of a patient with cerebrotendinous xanthomatosis
      was carried out by a nuclear magnetic resonance study. The bile sample was
      extracted with ethanol and chromatographed on an ion-exchange column, a reverse
      phase partition column and a silica gel column to isolate glucurono-conjugates of
      5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol, 5 beta-cholestane-3
      alpha, 7 alpha 12 alpha, 23-tetrol, and 5 beta-cholestane-3 alpha, 7 alpha, 12
      alpha, 23, 25-pentol. Proton and 13C nuclear magnetic resonance spectra of the
      two biliary bile alcohol glucuronides, 5 beta-cholestane-3 alpha, 7 alpha, 12
      alpha, 25-tetrol glucuronide and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,
      23, 25-pentol glucuronide were identical with those of the synthetic glucuronide
      7 alpha, 12 alpha, 25-trihydroxy-5 beta-cholestane-3 alpha-O beta-D
      glucopyranosyluronic acid and the isolated glucuronide 3 alpha, 7 alpha, 12
      alpha, 25-tetrahydroxy-5 beta-cholestane-23-O-beta-D-glucopyranosyluronic acid
      from urine of a patient with cerebrotendinous xanthomatosis, respectively. Hence,
      the glucurono-conjugated positions of the biliary 25-tetrol glucuronide and the
      biliary 23,25-pentol glucuronide were C-3 and C-23, respectively. By comparison
      of the 13C chemical shift data with that of the unconjugated bile alcohol, 5 beta
      cholestane-3 alpha, 7 alpha, 12 alpha, 23-tetrol, the glucurono-conjugated
      position of the natural 23-tetrol glucuronide was determined to be C-23. Thus,
      the natural 23-tetrol glucuronide can be formulated as 3 alpha, 7 alpha, 12 alpha
      trihydroxy-5 beta-cholestane-23-O-beta-D-glucopyranosyluronic acid.

PMID- 8539779
TI  - The synthesis and reactivity of 3 beta-(2-alkynylsulfonyl)- and 3 beta-(2
      alkynylsulfonylmethyl) androst-5-en-17-ones as inhibitors of glucose-6-phosphate
      dehydrogenase.
AB  - 3 beta-(Hexadec-2-ynylsulfonyl)androst-5-en-17-one, 2c, was designed as an analog
      of dehydroepiandrosterone sulfatide 1c, a potent, natural inhibitor of glucose-6
      phosphate dehydrogenase (G6PDH). Nucleophilic substitution of 1-bromo hexadec-2
      yne 11 with 3 beta-mercaptoandrost-5-en-17-one followed by oxidation afforded 2c.
      The propargylic sulfone 2c may tautomerize to the electrophilic allenic sulfone
      3a and thus function as a masked affinity label of the steroidal binding site of
      G6PDH. Since 2c demonstrated low potency as an inhibitor of G6PDH, a
      sulfonylmethyl analog 4b was also designed and synthesized. Synthesis of 4b began
      by methylenation of androst-5-en-3,17-dione 17-ketal 6 with the Tebbe reagent, to
      yield the 3-methyleneandrost-5-ene 7. Hydroboration, followed by oxidation, gave
      a mixture of 3 alpha- and 3 beta-hydroxymethyl isomers 8a and 8b, respectively.
      The 3 beta alcohol 8b was converted to the thiol 10. Alkylation of 10 with 1
      bromo-2-hexadecyne 11, followed by selective oxidation, gave the desired
      acetylenic sulfone 4b. Insertion of the methylene in 4a and 4b significantly
      increased their G6PDH inhibitory properties over the initial compounds, 2b and
      2c.

PMID- 8539781
TI  - A comparative structural study on the steroids [1,2,5]oxadiazolo[3', 4':3,4]-5
      alpha-pregn-16-en-20-one oxime (HS998), [1,2,5]oxadiazolo[3, 4':3,4]-5 beta-pregn
      16-en-20-one (HS973) by NMR, molecular modeling, and X-ray investigations.
AB  - The molecular structure of the steroids [1,2,5]oxadiazolo[3', 4':3,4]-5 alpha
      pregn-16-en-20-one oxime, [1,2,5]oxadiazolo[3',4':3, 4':3,4]-5 alpha-pregn-16-en
      20-one and [1,2,5]oxadiazole]3',4':3,4]-5 beta-pregn-16-en-20-one has been
      determined. The proton-proton distances in the solid state from previous
      crystallographic studies are compared with the corresponding distances from novel
      and previous solution NMR as well as from novel in vacuo modeling studies.

PMID- 8539782
TI  - Expression of corticosteroid-binding globulin mRNA in human uterine endometrial
      cancers.
AB  - Since it has been demonstrated that corticosteroid-binding globulin (CBG) plays a
      role in intracellar steroidal actions in target cells, the expression of CBG mRNA
      as the measure of CBG expression was investigated in human endometrial cancers in
      order to assess the biological implications of CBG. The level of CBG mRNA was
      analyzed using competitive reverse transcription-polymerase chain reaction
      Southern blot analysis. While the level of CBG mRNA was significantly (P < 0.01)
      higher in secretory phase endometrium than in early and late proliferative phase
      endometrium, the level of CBG mRNA tended to decrease with advanced
      dedifferentiation of endometrial cancers as compared to normal endometrium. These
      results suggest that dedifferentiation of endometrial cancers induces a reduction
      in intracellular CBG synthesis.

PMID- 8539783
TI  - A novel synthesis of 14 alpha, 15 alpha-methylene estradiol (J 824).
AB  - A novel approach to the synthesis of the orally active estrogen 14 alpha,15 alpha
      methylene estradiol (8, J 824) is described, starting with 3-methoxy-estra
      1,3,5(10),8,14-pentaen-17 alpha-ol (5). The 14 alpha, 15 alpha-methylene bridge
      was sonochemically introduced by regioselective and stereoselective Simmons-Smith
      methylenation of the 14-double bond. Birch reduction of the 8-double bond
      provided the desired 8 beta-H, 9 alpha-H steroid, whereas ionic hydrogenation
      afforded the 8 beta-H, 9 beta-H isomer, together with an epimerization of the 17
      alpha-hydroxy group. Oxidation of the Birch product yielded the corresponding 17
      oxo steroid, which gave the title compound by diborane reduction. For
      radioimmunoassay development the 6-(O-carboxymethyl)-oximino derivative of 8 was
      prepared as hapten and the 2-hydroxy derivative of 8 was synthesized as a
      potential metabolite of 8, and 8 was tritium labeled as well.

PMID- 8539784
TI  - New polar steroids from the sponges Trachyopsis halichondroides and Cymbastela
      coralliophila.
AB  - Fractions of trisulfated trihydroxysteroids from the sponges Trachyopsis
      halichondroides (two different collections) and Cymbastela coralliophila have
      been isolated and investigated. Ten triacetates were obtained from these
      fractions by desulfatation/acetylation followed by chromatographic separation,
      and their structures have been established. Four of these derivatives--namely,
      triacetates of 5 alpha-pregnane-2 beta,3 alpha,6 alpha-triol (3c), 23,24-dinor-5
      alpha-cholane-2 beta,3 alpha,6 alpha-triol (4c), 5 alpha-cholest-22-ene-2 beta,3
      alpha,6 alpha-triol (7c), and 24-isopropyl-5 alpha-cholestane-2 beta,3 alpha,6
      alpha-triol (11c)-- are described as new derivatives of natural steroids.

PMID- 8539785
TI  - The syntheses of 3 beta-steroidal diacylglyceryl sulfides, sulfoxides, and
      sulfones.
AB  - The syntheses of the diacylglyceryl-sulfide 4a, sulfoxide 4b, and sulfone 4c of
      dehydroepiandrosterone (3 beta-hydroxyandrost-5-en-17-one, DHEA, 1a) are
      described. Nucleophilic substitution of 1,2-dipalmitoyl-3-iodo-rac-3
      deoxyglycerol (2) with 3 beta-mercaptoandrost-5-en-17-one (3) afforded the
      diacylglyceryl-sulfide (4). Selective oxidation of 4 with m-chloroperbenzoic acid
      gave the diacylglyceryl-sulfoxide 4b and diacylglyceryl-sulfone 4c of DHEA. The
      sulfide 4a was a very weak inhibitor of glucose-6-phosphate dehydrogenase,
      whereas the sulfone 4c did not inhibit the enzyme.

PMID- 8539786
TI  - Biological evaluation of epoxy analogs of 1 alpha,25-dihydroxyvitamin D3.
AB  - The biological activity of 16-epoxy side-chain analogs of 1 alpha,25
      dihydroxyvitamin D3, (1 alpha,25(OH)2D3) was evaluated in vitro and in vivo.
      Compared to 1 alpha,25(0H)2D3, all analogs had lower affinities for the pig
      duodenal vitamin D receptor and also for the human serum vitamin D binding
      protein. The in vitro effects on cell proliferation or differentiation of human
      promyeloid leukemia (induction of superoxide production in HL-60 cells), human
      osteosarcoma MG-63 cells (osteocalcin secretion), or human breast cancer cells
      (incorporation of thymidine in MCF-7 cells), was markedly inhibited by several
      epoxy analogs, compared to 1 alpha,25(OH)2D3, but the rank order of their
      activity widely varied among different cancer cells. The most potent analogs
      (24S,25S-24-hydroxy-25,26-epoxy-22-ene-1 alpha-OHD3, 25,26-epoxy-23-yne-1 alpha
      OHD3, and 25,26-epoxy-23-yne-20-epi-1 alpha-OHD3 or compounds, 16, 5, and 7,
      respectively) were equipotent (16 and 5) or 30-fold (compound 7 on MG-63 cells)
      to 40-fold (compound 7 on MCF-7 cells) more active than 1 alpha,25-(OH)2D3. These
      analogs were nevertheless poorly antirachitic (< 3%) when tested in vitamin D
      deficient chicks (using serum and bone calcium, serum osteocalcin and duodenal
      calbindin D-28K, as end points). Compound 7 was also 100-fold more active than 1
      alpha,25-(OH)2D3 in inhibition of proliferation of human foreskin keratinocytes.
      Some epoxy analogs of 1 alpha,25-(OH)2D3 thus display interesting dissociations
      between their receptor affinity and their potency to induce cell differentiation,
      whereas their effect on cell proliferation/differentiation exceed their calcemic
      effects more than 100- to 1000-fold.

PMID- 8539787
TI  - Studies on the synthesis of dehydroepiandrosterone (DHEA) phosphatide.
AB  - Synthetic dehydroepiandrosterone (DHEA) phosphatide 1c, (R = C15H31), was
      prepared by three methods. The most efficient of these involved the coupling of
      the commercially available DHEA 1a and commercially available phosphatidic acid
      2, via mesitylene sulfonyl chloride and pyridine. Alternatively, DHEA-3-phosphate
      1b was coupled with dipalmitoyl glycerol 3 in the same way. The third synthesis
      gave 1c by coupling DHEA with the cyclic phosphotriester 4 followed by
      deblocking.

PMID- 8539788
TI  - Microbial transformation of steroids: contribution to 14 alpha-hydroxylations.
AB  - The regioselective and stereoselective hydroxylation of steroids by fungal
      strains previously known for their hydroxylation capabilities, such as
      Thamnostylum (= Helicostylum) piriforme ATCC 8992, Mucor griseocyanus ATCC 1207a,
      Actinomucor elegans (= Mucor parasiticus) MMP 3122 (Mucorales), and Zygodesmus
      sp. ATCC 14716, was investigated with special interest for the 14 alpha
      hydroxylation reaction. A preliminary screening had shown that some of these
      microorganisms were adequate for the production of 14 alpha-hydroxylated
      derivatives of the following steroids: progesterone, 5 beta-pregnane-3,20-dione,
      3 beta-hydroxy-5 beta-pregnane-20-one, 3 beta-hydroxy-5 beta-17 (alpha H)-etianic
      acid methyl ester, androst-4-ene-3,17-dione, and testosterone. About 20
      metabolites have been isolated and purified by silicagel chromatography and semi
      preparative reverse-phase HPLC. These metabolites have been fully characterized
      by 1H, 13C NMR and mass spectrometry. All the identified metabolites were
      hydroxylated at some distinct positions, such as 6 beta-, 7 alpha-, 9 alpha-, 14
      alpha-, 15 beta-, or dihydroxylated at 6 beta,14 alpha-,7 alpha,14 alpha-, 9
      alpha,14 alpha-, 14 alpha,15 alpha-, 14 alpha,15 beta-positions; nine of these
      metabolites have not been reported previously. The relationship between the
      structural features of the investigated steroids and the site-specific
      hydroxylation has been delineated, and progesterone was found to be the best
      substrate for the production of 14 alpha-hydroxylated derivative, using T.
      piriforme.

PMID- 8539789
TI  - Metabolism of anabolic steroids in humans: synthesis of 6 beta-hydroxy
      metabolites of 4-chloro-1,2-dehydro-17 alpha-methyltestosterone, fluoxymesterone,
      and metandienone.
AB  - Hydroxylation at position 6 beta testosterone I (17 beta-hydroxyandrost-4-en-3
      one) and the anabolic steroids 17 alpha-methyltestosterone II (17 beta-hydroxy-17
      alpha-methylandrost-4-en-3-one), metandienone III (17 beta-hydroxy-17 alpha
      methylandrosta-1,4-dien-3-one), 4-chloro-1,2-dehydro-17 alpha-methyltestosterone
      IV (4-chloro-17 beta-hydroxy-17 alpha-methylandrosta-1,4-dien-3-one), and
      fluoxymesterone V (9-fluoro-11 beta, 17 beta-dihydroxy-17 alpha-methylandrost-4
      en-3-one) was achieved via light-induced autooxidation of the corresponding
      trimethysilyl 3,5-dienol ethers dissolved in isopropanol or ethanol. The reaction
      further yielded the 6 alpha-hydroxy isomer in low amounts. The 6 beta-hydroxy
      isomer of I-V and the 6 alpha-hydroxy isomers of I, III, and IV were isolated and
      characterized by 1H and 13C NMR, high-performance liquid chromatography, gas
      chromatography, and mass spectrometry. Human excretion studies with single
      administered doses of boldenone (17 beta-hydroxyandrosta-1,4-dien-3-one), 4
      chloro-1,2-dehydro-17 alpha-methyltestosterone, fluoxymesterone, metandienone, 17
      alpha-methyltestosterone, and [16,16,17-2H3] testosterone showed that 6 beta
      hydroxylation is the major metabolic pathway in the metabolism of 4-chloro-1,2
      dehydro-17 alpha-methyltestosterone, fluoxymesterone, and metandienone, whereas
      for boldenone, 17 alpha-methyltestosterone, and testosterone, 6 beta
      hydroxylation is negligible.

PMID- 8539790
TI  - Thirty years of steroid hormone action: personal recollections of an
      investigator.

PMID- 8539791
TI  - Competing pathway involved in allylic acetoxylation of androst-5-en-17-one, and
      oxidation of allylic alcohols with chromium oxides.
AB  - Allylic acetoxylation of androst-5-en-17-one (1) with bromine and silver acetate
      gave 6 alpha- and 6 beta-acetoxyandrost-4-en-17-ones [4 (3%) and 5 (12%)] and 5
      alpha-bromo-6 beta-acetoxy steroid 8 (4%) along with the expected product 4 beta
      acetoxy derivative 2 (45%). Treatment of 5 alpha,6 beta-bromide 12, an
      intermediate of the acetoxylation reaction, with silver acetate also produced the
      acetates 2, 4, 5, and 8 in relative yields similar to those above. These results
      indicate that the 6-acetates 4 and 5 are produced through a competing pathway
      involving formation of a bridged carbonium ion 13 followed by attack of an
      acetate anion. Oxidation of the axial allylic alcohol, 5-en-4 beta-ol 3, with
      Jones reagent yielded no trace of the previously reported androst-5-ene-4,17
      dione (18) but instead gave a 1:4 mixture of 5 beta,6 beta-epoxy-4-one 16 and 4
      beta,5 beta-epoxy-6-one 17 in high yield. In contrast, a 1:4 mixture of androst-4
      ene-6,17-dione (10) and compound 18 was obtained upon treatment with chromium
      trioxide in pyridine. Similar results were also found with the oxidation of
      another axial allylic alcohol, 4-en-6 beta-ol 7.

PMID- 8539792
TI  - Further studies on 6-alkylandrost-4-ene-3,17-diones as aromatase inhibitors:
      elongation of the 6-alkyl chain.
AB  - To gain further insight on the relationship between 6-alkylandrost-4-ene-3,17
      diones and their aromatase inhibition activity, a series of alkyl steroids with
      long alkyl chains (n-pentyl, n-hexyl, or n-octyl) at C-6 alpha and 6 beta were
      synthesized. All of the steroids studied inhibited human placental aromatase in a
      competitive manner with apparent Ki values ranging from 2.8 to 80 nM. The 6 beta
      pentyl analog 4a (Ki = 2.8 nM) was the most potent inhibitor. The inhibitory
      activities of the 6 beta-alkyl steroids 4 were more powerful than those of the
      corresponding 6 alpha-isomers 5. The addition of one methylene unit to the 6
      alpha- and 6 beta-n-butyl moieties of androst-4-ene-3,17-dione markedly increased
      the affinity to aromatase, whereas further elongation of the n-pentyl group
      decreased affinity in relation to the carbon number of the alkyl chain. These
      results, along with molecular modeling with the PM3 method, suggest that the
      increased affinities of the pentyl steroids 4a and 5a may essentially depend on
      the formation of thermodynamically stable enzyme-inhibitor complex in the
      hydrophobic binding pocket.

PMID- 8539793
TI  - Antiestrogenic activity of two 11 beta-estradiol derivatives on MCF-7 breast
      cancer cells.
AB  - Two 11 beta-derivatives of estradiol (E2) were tested for their potential
      antiestrogenic activity in the MCF-7 breast cancer model: one contained a
      phenoxydimethylaminoethyl side-chain (RU 39,411), the other a
      pentafluoropentylsulfinyl side-chain (RU 58,668). The former compound displayed
      mixed estrogenic/antiestrogenic properties, while the latter indicated only an
      antiestrogenic activity. Both the compounds produced a growth inhibition of MCF-7
      cells at doses related to their binding affinity for the estrogen receptor (ER);
      E2 suppressed this inhibition. The compounds also down-regulated the estrogen
      binding capacity of the cells but failed to reduce ER mRNA levels, indicating
      that the grafting of their side-chains prevented this antagonistic effect usually
      observed with steroidal estrogens. Assessment of ER levels by enzyme immunoassay
      revealed a marked increase with RU 39,411 and a decrease with RU 58,668;
      different mechanisms of action should, therefore, be considered. Finally, the
      estrogenic activity of RU 39,411 was demonstrated by its strong ability to induce
      synthesis of the progesterone receptor; RU 58,668 failed to display this
      agonistic activity.

PMID- 8539794
TI  - 17 beta-estradiol treatment increases the levels of estrogen receptor and its
      mRNA in male rat liver.
AB  - This study examined estrogen receptor dynamics in the livers of male obese rats
      (SHHF/Mcc-cp) treated for two weeks with a continuous, low dose of 17 beta
      estradiol compared with untreated controls. An increased binding capacity for
      tritiated 17 beta-estradiol in the cytosol, consistent with binding to the
      estrogen receptor, was demonstrated in treated males relative to control males (P
      < 0.01). These observations were confirmed using curve-peeling techniques with
      saturation analysis, ammonium sulfate precipitation/fractionation of cytosol
      protein, and chromatographic techniques to isolate the high-affinity binding from
      other interfering factors. Increased hepatic nuclear estrogen receptor levels in
      treated males (112.3 +/- 8.3 fmol/g liver) compared with controls (64.1 +/- 6.8
      fmol/g liver) suggested that the liver was under estrogenic influences. This
      interpretation was supported by an increase in serum triglyceride levels,
      reflecting increased very low density lipoprotein secretion by the liver.
      Reductions in testosterone levels and in the weights of seminal vesicles and the
      testes in treated males indicated detrimental effects on reproduction. An
      interpretation of increased synthesis of estrogen receptor with 17 beta-estradiol
      treatment was supported by the observation of an increase in the mRNA for
      estrogen receptor. Taken together, these observations indicate that continuous,
      low-dose 17 beta-estradiol treatment induces estrogenic action in the livers of
      male rats and also increases hepatic estrogen receptor, probably indirectly, via
      an increase in its mRNA.

PMID- 8539795
TI  - Aminopropylation of vitamin D hormone (1 alpha,25-dihydroxyvitamin D3), its
      biological precursors, and other steroidal alcohols: an anchoring moiety for
      affinity studies of sterols.
AB  - In this communication we describe a simple two-step procedure for the conversion
      of several steroidal alcohols to their aminopropyl ether derivatives. To
      demonstrate the usefulness of this procedure we synthesized a second-generation
      photoaffinity labeling analog of 1 alpha,25-dihydroxyvitamin D3, and a 25
      hydroxyvitamin D3 derivative containing a long and chemically stable tether.
      Utilities of these aminopropyl ether derivatives of steroids in various affinity
      studies of receptor proteins are discussed.

PMID- 8539796
TI  - Accelerated stability studies on 16-methylene-17 alpha-acetoxy-19-nor-pregn- 4
      ene-3,20-dione (Nestorone).
AB  - The stability of the contraceptive steroid, Nestorone (16-methylene-17 alpha
      acetoxy-19-nor-pregn-4-ene-3,20-dione) in the solid state and in aqueous
      solutions, was investigated using reverse-phase high-performance liquid
      chromatography. In the solid state, whether as a powder or when it is
      incorporated into Silastic implants, the steroid does not undergo detectable
      degradation even under severe experimental conditions. In solution, the drug
      undergoes slow degradation that is dependent on temperature and pH of the medium.
      The decomposition is defined by first-order mechanism. As expected, the reaction
      rate increases with increasing storage temperature. The linearity of the
      Arrhenius plot indicates that there is no change in the reaction mechanism within
      the temperature range studied. In alkaline media, the drug degrades at a faster
      rate through hydrolytic rather than an oxidative mechanism. The major hydrolytic
      degradation product, 16-methylene-17 alpha-hydroxy-19-nor-pregn-4-ene-3,20-dione,
      was separated and identified by mass spectrometry.

PMID- 8539797
TI  - Immunosuppressive regimens of tomorrow.

PMID- 8539798
TI  - Long-term function (> 5 years) of pancreas grafts from the International Pancreas
      Transplant Registry database.

PMID- 8539800
TI  - Experience with clinical pancreatic transplantation using the bladder drainage
      technique.

PMID- 8539799
TI  - Conversion from cyclosporine to tacrolimus after pancreas transplantation.

PMID- 8539801
TI  - Efficacy and safety of dithizone in staining of islet cell transplants.

PMID- 8539802
TI  - Use of glucose disappearance rates to monitor beta-cell function of pancreas
      allografts.

PMID- 8539803
TI  - Experimental heterotopic autotransplantation of tail of the pancreas:
      immunohistochemical findings.

PMID- 8539804
TI  - Experimental heterotopic allotransplantation of the tail of the pancreas:
      immunohistochemical results.

PMID- 8539805
TI  - Proliferation of rat pancreatic ductal-epithelial cells in vitro, and in response
      to partial hepatectomy and pancreatectomy in vivo.

PMID- 8539806
TI  - Prophylaxis for cytomegalovirus in pancreas transplant recipients using
      intravenous ganciclovir.

PMID- 8539807
TI  - Cystoscopic management of pancreatic allograft duct obstruction.

PMID- 8539808
TI  - Carotid intima-media thickness by ultrasound measurement in pancreas transplant
      candidates.

PMID- 8539810
TI  - Learning curve in pancreatic transplantation at a single center.

PMID- 8539809
TI  - Lipids following pancreas transplantation in recipients receiving FK 506.

PMID- 8539811
TI  - Rat whole pancreaticoduodenal allotransplantation treated with 15-deoxyspergualin
      alone and with splenectomy.

PMID- 8539812
TI  - Pancreas transplantation with portal venous drainage and enteric exocrine
      drainage offers early advantages without compromising safety or allograft
      function.

PMID- 8539813
TI  - Effects of long-term exposure to urine on proliferative lesions of the duodenum
      in bladder-drained pancreas transplants.

PMID- 8539814
TI  - Intracellular adhesion molecule 1 expression on rat pancreatic allografts.

PMID- 8539815
TI  - Iliac artery-bladder fistula: a late complication of rejected pancreas
      transplants with bladder drainage.

PMID- 8539816
TI  - Effect of major histocompatibility disparity on mycophenolate mofetil
      immunosuppression in rat pancreas transplantation.

PMID- 8539817
TI  - Experience with protocol biopsies after solitary pancreas transplantation.

PMID- 8539818
TI  - Experience with enteric conversion after pancreas transplantation with bladder
      drainage.

PMID- 8539819
TI  - Increased risk of pulmonary edema in diabetic patients undergoing preemptive
      pancreas transplantation with OKT3 induction.

PMID- 8539820
TI  - Infection prophylaxis in pancreas transplant recipients.

PMID- 8539821
TI  - Experience with pancreas retransplantation.

PMID- 8539822
TI  - Solitary pancreas transplantation: experience with 50 consecutive cases.

PMID- 8539823
TI  - Preliminary experience with FK 506 in pancreas transplant recipients.

PMID- 8539824
TI  - Influence of delayed completion pancreatectomy on engraftment of islets isolated
      from the previously excised segment in dogs: histological findings.

PMID- 8539825
TI  - Simplifying the technique for pancreaticoduodenal transplantation with enteric
      exocrine drainage.

PMID- 8539826
TI  - Metabolic control in recipients of segmental pancreatic grafts functioning beyond
      8 years.

PMID- 8539828
TI  - Conversion of pancreas transplants to FK 506 from CsA.

PMID- 8539827
TI  - FK 506-based immunosuppression in clinical pancreas transplantation.

PMID- 8539829
TI  - The magnetic resonance-derived pancreas to psoas ratio (PPR): objective and
      reliable noninvasive diagnosis of pancreatic rejection.

PMID- 8539830
TI  - The efficacy of CMH (Collins modified with HES) solution in canine pancreatic
      graft preservation.

PMID- 8539831
TI  - Serum sialic acid, a risk factor for cardiovascular disease, improves following
      pancreas transplantation.

PMID- 8539832
TI  - Sensitivity and responsiveness of glucose removal to insulin decrease following
      systemic pancreatic venous drainage.

PMID- 8539833
TI  - Hemipancreatectomy, peripheral diversion of pancreatic venous drainage, and
      insulin sensitivity.
AB  - It has been previously noted that a mild insulin deficiency could increase
      insulin sensitivity in rats. The data shown here are consistent with such an
      observation in that the insulin resistance, which was induced by diversion of
      pancreatic venous drainage to the peripheral circulation, was corrected by the
      insulin deficiency which was secondary to the hemipancreatectomy performed. These
      results also help to explain some of the apparent inconsistencies that appear to
      be present in the comparison often made of insulin sensitivity following various
      transplantation procedures. Both the site of pancreatic venous drainage and any
      decrease in beta-cell mass which may accompany pancreas or islet transplantation
      appear to have independent and opposite effects on insulin sensitivity.

PMID- 8539834
TI  - Conservative management of intrapancreatic collections after whole pancreas
      transplantation: report of two cases.

PMID- 8539835
TI  - Pregnancy after pancreas transplantation: report of four new cases and review of
      the literature.

PMID- 8539836
TI  - How to treat graft infection after pancreatic transplantation.

PMID- 8539837
TI  - Enteric drainage of pancreas transplants revisited.

PMID- 8539838
TI  - Advantages of the rapid en bloc technique for pancreas/liver recovery.

PMID- 8539839
TI  - Tissue hydration in UW-preserved pancreas allografts: evaluation by magnetic
      resonance relaxometry.

PMID- 8539840
TI  - Hand-sewn versus stapled duodenocystostomy in bladder-drained pancreas
      transplants.

PMID- 8539841
TI  - Fine-needle aspiration biopsy in pancreatic transplantation.

PMID- 8539842
TI  - Diagnosis and treatment of symptomatic peripancreatic fluid collections after
      pancreas transplant.

PMID- 8539843
TI  - Cost analysis of kidney-pancreas and kidney-islet transplant.

PMID- 8539844
TI  - Identification of quality-of-life outcomes distinguishing diabetic kidney-alone
      and pancreas-kidney recipients.

PMID- 8539845
TI  - One-year change in quality-of-life profiles in patients receiving pancreas and
      kidney transplants.

PMID- 8539846
TI  - Low postoperative wound infection rates are possible following simultaneous
      pancreas-kidney transplantation.

PMID- 8539847
TI  - Outcome of combined kidney/pancreas transplantation in recipients with coronary
      artery disease.

PMID- 8539848
TI  - Evolution of carotid vascular lesions in kidney-pancreas and kidney-alone
      transplanted insulin-dependent diabetic patients.

PMID- 8539849
TI  - Insulin secretion and glucose tolerance evolution in kidney-pancreas graft.

PMID- 8539850
TI  - Long-term function and rehabilitation in combined kidney and pancreatic
      transplants.

PMID- 8539851
TI  - Impact of ganciclovir prophylaxis on cytomegalovirus infection in cadaveric
      kidney vs combined kidney and pancreas transplantation.

PMID- 8539852
TI  - Factors affecting oral glucose tolerance after pancreas-kidney transplantation.

PMID- 8539853
TI  - First experience with combined pancreatic-renal transplantation with
      extraperitoneal placement of the whole pancreatic graft.

PMID- 8539854
TI  - Selection for low cardiovascular risk markedly improves patient and graft
      survival in pancreaticorenal transplant recipients.

PMID- 8539855
TI  - Pre and posttransplant urologic work-up in simultaneous kidney/pancreas
      transplant: preliminary results of an ongoing study.

PMID- 8539856
TI  - High intravesical pressures and related urologic complications in simultaneous
      kidney/pancreas transplant recipients.

PMID- 8539857
TI  - Successful pancreas-renal transplantation without anti-T-cell antibody induction.

PMID- 8539858
TI  - Major bacterial and fungal infections after 50 simultaneous pancreas-kidney
      transplantations.

PMID- 8539859
TI  - Improvement in nerve conduction 8 years after combined pancreatic and renal
      transplantation.

PMID- 8539860
TI  - Use of granulocyte-macrophage colony-stimulating factor for reversal of
      neutropenia following combined kidney-pancreas transplantation.

PMID- 8539861
TI  - Cyclosporine resorption in diabetic patients after simultaneous pancreas and
      kidney transplantation.

PMID- 8539862
TI  - Is there a transfusion effect in combined pancreas-kidney transplantation?

PMID- 8539863
TI  - Donor criteria and technical aspects of procurement in combined pancreas and
      kidney transplantation from non-heart-beating cadavers.

PMID- 8539864
TI  - Positive duodenal segment cultures are not associated with increased surgical
      complications after whole organ, bladder-drained pancreas transplantation in
      three recipient categories.

PMID- 8539865
TI  - Risk factors of long-term survivals in combined kidney/pancreas transplantation:
      a multivariate analysis of 259 recipients.

PMID- 8539866
TI  - Urologic infections and problems after 50 simultaneous pancreas-kidney
      transplantations.

PMID- 8539867
TI  - Decreased graft survival rate in obese pancreas/kidney recipients.

PMID- 8539869
TI  - Analysis of the rejection markers tumor necrosis factor, ICAM-1, neopterin,
      interleukin-10, and soluble HLA in simultaneous pancreas and kidney
      transplantation with bladder drainage.

PMID- 8539868
TI  - Cost-effective treatment for diabetic end-stage renal disease: dialysis, kidney,
      or kidney-pancreas transplantation?

PMID- 8539870
TI  - Low urinary tract infections in simultaneous pancreas and kidney transplantation:
      comparison between bladder and enteric drainage of exocrine secretions.

PMID- 8539871
TI  - Late complications in kidney-pancreas transplant recipients.

PMID- 8539872
TI  - Use of FK 506 in simultaneous pancreas/kidney transplantation: lack of impairment
      of glycemic or lipid metabolism.

PMID- 8539873
TI  - Donor bone marrow infusion in simultaneous pancreas/kidney transplant recipients:
      a preliminary study.

PMID- 8539874
TI  - The use of FK506 in simultaneous pancreas/kidney transplantation: rescue,
      induction, and maintenance immunosuppression.

PMID- 8539875
TI  - Urological complications following simultaneous pancreas-kidney transplantation.

PMID- 8539876
TI  - Stability of bladder function two years following simultaneous pancreas-kidney
      transplantation.

PMID- 8539877
TI  - Multivariate analysis of donor and recipient risk factors for renal and pancreas
      allograft failure after pancreas-kidney transplantation.

PMID- 8539878
TI  - Wound complications after simultaneous pancreas-kidney transplants: midline
      versus transverse incision.

PMID- 8539879
TI  - Comparison between methylprednisolone and OKT3 treatment for the first acute
      rejection episode in combined kidney and pancreas transplant recipients.

PMID- 8539880
TI  - Combined pancreas-kidney transplants using quadruple immunosuppression therapy: a
      comparison between antilymphoblast and antithymocyte globulins.

PMID- 8539881
TI  - Clinical and laboratory features of pancreatic transplant bladder leaks.

PMID- 8539882
TI  - A comparison of the sensitivities of contrast and isotope voiding
      cystourethrograms for the detection of pancreas transplant bladder leaks.

PMID- 8539883
TI  - Long-term effects of fetal islet transplantation on complication of diabetes, as
      compared with effects of intensive insulin therapy.

PMID- 8539884
TI  - Human fetal islet transplantation in IDDM patients: an 8-year experience.

PMID- 8539885
TI  - Indications for human islet transplantation: chronic pancreatitis and cystic
      fibrosis.

PMID- 8539886
TI  - Islet and kidney transplantation using ATG and cyclosporin monotherapy and a
      central facility for islet isolation and purification.

PMID- 8539887
TI  - Long-term function of islet allograft in type I diabetes mellitus.

PMID- 8539888
TI  - Natural history of insulin independence after transplantation of multidonor
      cryopreserved pancreatic islets in type 1 diabetic humans.

PMID- 8539889
TI  - Clinical islet autotransplantation after pancreatectomy: determinants of success
      and implications for allotransplantation?

PMID- 8539890
TI  - Human islet transplantation: results of the first 37 patients.

PMID- 8539891
TI  - Insulin independence for 58 months following pancreatic islet cell
      transplantation in a patient undergoing upper abdominal exenteration.

PMID- 8539892
TI  - Islet transplantation in type II diabetes.

PMID- 8539893
TI  - Reversal of type II (NIDDM) diabetes by pancreas islet transplantation: an
      emerging new concept in pathophysiology of an enigmatic disease.

PMID- 8539894
TI  - Use of an on-line computer system for quantifying insulin requirements before and
      after islet cell transplantation: first experience.

PMID- 8539895
TI  - Canine islet allograft survival after donor specific vertebral body derived bone
      marrow cell transplantation without irradiation conditioning of the recipient.

PMID- 8539896
TI  - Comparison of histidine-tryptophane-ketoglutarate (HTK) and University of
      Wisconsin (UW) solution for pancreas perfusion prior to islet isolation, culture
      and transplantation.

PMID- 8539897
TI  - Effects of islet transplantation on advanced glycosylation end products in
      diabetic rats.

PMID- 8539898
TI  - Pig islet isolation and allotransplantation.

PMID- 8539899
TI  - Substantial peripheral T-cell depletion before grafting is beneficial in islet
      transplantation.

PMID- 8539900
TI  - Transplantation of fetal and neonatal islet tissue: functional and morphological
      evaluation of free and encapsulated islet grafts.

PMID- 8539901
TI  - Long-term normalization of GLUT 4 protein content in skeletal muscle of
      streptozotocin-diabetic Lewis rats after islet transplantation.
AB  - Islet transplantation under the kidney capsule of STZ-diabetic Lewis rats was
      able to maintain near-normoglycemia over a period of 6 months. Fasting insulin in
      these animals was higher compared to controls but did not increase after feeding.
      Plasma glucose following an OGTT at 2 months was only slightly impaired, and
      after 6 months was more severely impaired in the Tx rats. An IVGTT 6 months after
      Tx confirmed impaired glucose tolerance and showed a loss of first phase insulin
      release. GLUT 4 protein content in skeletal muscle was completely restored in Tx
      animals. In conclusion, long-term near-normoglycemia after syngeneic islet
      transplantation under the kidney capsule of STZ-diabetic Lewis rats is associated
      with complete normalization of skeletal muscle GLUT 4 protein content, even in
      the presence of abnormal glucose tolerance and impaired insulin secretion.

PMID- 8539902
TI  - Decreased chronic failure of intraperitoneal impure islets versus intrahepatic
      pure islets in a canine autograft model.

PMID- 8539903
TI  - Glycemic control mechanisms after canine islet autografting.

PMID- 8539904
TI  - T-cell vaccination prolongs heart but not islet allograft survival in rats.

PMID- 8539906
TI  - Nafamostat mesilate prevents warm ischemia-reperfusion injury in canine pancreas
      autotransplantation.

PMID- 8539905
TI  - Indefinite acceptance of heart but not skin or islet allografts in rats by total
      lymphoid irradiation without intrathymic injection of donor cells.

PMID- 8539907
TI  - Tolerance induction to islet allografts following infusion of perforin deficient
      bone marrow.

PMID- 8539908
TI  - Prevention and cure of type 1 diabetes in the BB rat by islet allotransplantation
      and glimepiride treatment.

PMID- 8539909
TI  - Islets deficient in cell-surface class I MHC (B2M-/-) induce unresponsiveness in
      allogeneic recipients.

PMID- 8539911
TI  - Repeated intrahepatic islet allografts restore normoglycemia in cyclosporine
      immunosuppressed diabetic pigs.

PMID- 8539910
TI  - Protective effects of nicotinamide on renal subcapsular islet isografts with a
      marginal mass from sustained hyperglycemia in the streptozotocin-induced diabetic
      rats.

PMID- 8539912
TI  - Intrathymic transplantation of rat perinatal islets, devoid of class II bearing
      cells, does not induce donor-specific tolerance.

PMID- 8539913
TI  - Beta-cell replication in long-term transplanted islets.

PMID- 8539914
TI  - Increase of islet yields obtained from human pancreas donor following change of
      pH value in collagenase digestion medium.

PMID- 8539915
TI  - Causes of islet allograft primary nonfunction.

PMID- 8539916
TI  - A new method for isolation of murine islets with markedly improved yields.

PMID- 8539917
TI  - Successful bovine islet xenografts in rodents and dogs using injectable
      microreactors.

PMID- 8539918
TI  - Successful reversal of diabetes in nude mice by transplantation of
      microencapsulated porcine neonatal islet cell aggregates.

PMID- 8539919
TI  - Beneficial metabolic impact of the novel immunosuppressant rapamycin in chronic
      canine islet autograft recipients.

PMID- 8539920
TI  - Efficacy of ICAM-1 antisense oligonucleotide in pancreatic islet transplantation.
AB  - Significant islet allograft prolongation was achieved by ICAM-1/LFA-1 blockade.
      ICAM-1 antisense oligonucleotide IP-3082 was effective in improving islet
      function as well as prolonging graft survival.

PMID- 8539921
TI  - Outcome of subcutaneous islet transplantation improved by a polymer device.

PMID- 8539922
TI  - Severity of hypoglycemia in rats when insulin is applied after islet
      allotransplantation in the liver.

PMID- 8539923
TI  - Toxic effects of superoxide, hydrogen peroxide, and nitric oxide on human and pig
      islets.

PMID- 8539924
TI  - Fine specificity of class I MHC recognition in islet allografts.

PMID- 8539925
TI  - Experimental intraportal allotransplantation of pancreatic islets in pigs:
      influence on liver function.

PMID- 8539926
TI  - Does immunoisolation need to prevent the passage of antibodies and complements?

PMID- 8539927
TI  - Membrane compactness affects the integrity and immunoprotection of alginate-poly
      L-lysine-alginate microcapsules.

PMID- 8539928
TI  - Transplantation of microencapsulated islets in rats: influence of low temperature
      culture before or after the encapsulation procedure on the graft function.

PMID- 8539929
TI  - Class I and class II antigens in the rejection of murine islet cell transplants.

PMID- 8539930
TI  - Liver-omental pouch and intrahepatic islet transplants produce portal insulin
      delivery and prevent hyperinsulinemia in rats.

PMID- 8539931
TI  - Portal insulin delivery prevents hyperinsulinemia in rats with renal-mesenteric
      vein anastomosis after renal islet transplants.

PMID- 8539932
TI  - Early changes in syngeneic islet grafts: effect of recipient's metabolic control
      on graft outcome.

PMID- 8539933
TI  - Prevention and treatment of type I diabetes in NOD mice by linomide.

PMID- 8539934
TI  - Retrospective analysis of in vitro function of isolated human islets from 56
      pancreata.

PMID- 8539935
TI  - Viability of islet-contaminated acinar cells as assessed by cholecystokinin
      stimulation.

PMID- 8539936
TI  - Image analysis of human pancreatic islets: a time-course approach to the
      evaluation of pancreatic dissociation.

PMID- 8539937
TI  - Household bleach effectively reduces microbial contamination in porcine islet
      isolation.

PMID- 8539938
TI  - The influence of hemodynamic status in heart-beating cadaveric organ donors on
      subsequent pancreatic islet yield.

PMID- 8539939
TI  - Hormone secretion from transplanted islets is dependent upon changes in islet
      revascularization and islet architecture.

PMID- 8539940
TI  - Cholinergic and adrenergic effects on insulin secretion from islet transplants.

PMID- 8539941
TI  - The effect of donor age on the outcome of islets isolated from human pancreata.

PMID- 8539942
TI  - Superiority of RPMI 1640 medium for packaging and transportation of islets at
      ambient temperature.

PMID- 8539943
TI  - Survival of islet grafts in perforin-deficient mice.

PMID- 8539944
TI  - Comparison of collagenase type P and Liberase during human islet isolation using
      the automated method.

PMID- 8539945
TI  - Factors in cadaveric donors that affect recovery of human islets of Langerhans.

PMID- 8539946
TI  - Recovery and in vivo function of canine islets cryopreserved in a freezer bag.

PMID- 8539947
TI  - Large-scale isolation of viable porcine neonatal islet cell (NIC) aggregates.

PMID- 8539948
TI  - Model for human islet neogenesis in vitro from adult pancreatic preparations.

PMID- 8539949
TI  - Short exposure to hepatocyte growth factor stimulates adult human pancreatic beta
      cell proliferation.

PMID- 8539950
TI  - Isolated human pancreatic islets in vitro activate human complement.

PMID- 8539951
TI  - Expression of apoptosis-inducing CD95 (Fas/Apo-1) on human beta-cells sorted by
      flow-cytometry and cultured in vitro.

PMID- 8539953
TI  - Biolistic transformation of pancreatic islets.

PMID- 8539952
TI  - Safety testing of Liberase, a purified enzyme blend for human islet isolation.

PMID- 8539954
TI  - Use of amphotericin B to clear fungal contamination of islet tissue isolated from
      contaminated source pancreas.

PMID- 8539955
TI  - The effect of a pancreatic allograft distal arteriovenous fistula on islet
      hormone secretions.

PMID- 8539956
TI  - Human pancreatic dissociation using a purified enzyme blend.

PMID- 8539957
TI  - A simple in vitro method for evaluating the efficacy of different batches of
      crude Clostridium histolyticum collagenase for islet isolation.

PMID- 8539958
TI  - University of Wisconsin solution inhibits the class II collagenase within crude
      Clostridium histolyticum collagenase.

PMID- 8539959
TI  - Recombinant enzymes for islet isolation: purification of a collagenase from
      Clostridium histolyticum and cloning/expression of the gene.

PMID- 8539960
TI  - Fludarabine phosphate and 2-chlorodeoxyadenosine: immunosuppressive DNA synthesis
      inhibitors with potential application in islet allo- and xenotransplantation.

PMID- 8539961
TI  - Engraftment and survival of human islet xenografts irradiated with ultraviolet B
      in immunocompetent diabetic mice.

PMID- 8539962
TI  - Successful xenografts in mice with microencapsulated rat and dog islets.

PMID- 8539963
TI  - Cellular requirements for pancreatic islet xenograft rejection.

PMID- 8539964
TI  - Lama glama (the South American camelid, llama): a unique model for evaluation of
      xenogenic islet transplants in a cerebral spinal fluid driven artificial organ.

PMID- 8539966
TI  - Immunomodulation with ionizing radiation does not prolong fish-to-mouse islet
      xenograft survival.

PMID- 8539965
TI  - Encapsulated islet iso-, allo-, and xenografts in diabetic NOD mice.

PMID- 8539967
TI  - Immunosuppression with leflunomide and cyclosporine prevents pig-to-rat islet
      xenograft rejection.

PMID- 8539968
TI  - In vivo function of pig islet xenografts in immunosuppressed diabetic mice.

PMID- 8539969
TI  - Xenogeneic discordant islet transplantation: natural antibodies and complement in
      a human-to-rat model.

PMID- 8539970
TI  - Assessment of pore size of a semipermeable membrane for immunoisolation on
      xenoimplantation of pancreatic B cells using a diffusion chamber.

PMID- 8539971
TI  - Transplantation of porcine and bovine islets into mice without immunosuppression
      using uncoated alginate microspheres.

PMID- 8539972
TI  - A simple and inexpensive method for transplanting xenogeneic cells and tissues
      into rats using alginate gel spheres.

PMID- 8539973
TI  - Induction of functional xenograft tolerance of pig islets in the autoimmune NOD
      mouse.

PMID- 8539974
TI  - Fasting and postprandial plasma glucose and peripheral insulin levels in insulin
      dependent diabetes mellitus and non-insulin-dependent diabetes mellitus subjects
      during continuous intraperitoneal versus subcutaneous insulin delivery.

PMID- 8539975
TI  - Isolation and function of islets from 6-week-old gnotobiotic pigs.

PMID- 8539976
TI  - Application of organic bound chrome in disturbed glycoregulation therapy.

PMID- 8539977
TI  - E-cadherin, NCAM, and EpCAM expression in human fetal pancreata.

PMID- 8539978
TI  - Effect of cryopreservation on islet recovery and in vivo function.

PMID- 8539979
TI  - Effects of bicarbonate and amino acid buffered media on survival and viability of
      long-term bulk cultured human islets.

PMID- 8539980
TI  - Isolated porcine pancreatic islets in long-term culture: effects of temperature
      on survival, viability, and function of islets.

PMID- 8539981
TI  - Human vertebral body bone marrow harvest: comparison between manual and automated
      methods.

PMID- 8539982
TI  - A model of islet vascularization in vitro: contrasting metabolic effects of mixed
      islet/vascular cell cocultures on xenogeneic versus allogeneic vascular
      endothelium.

PMID- 8539983
TI  - In vivo maturation and growth potential of human fetal pancreases: fresh versus
      cultured tissue.

PMID- 8539984
TI  - Expression of a fluorescent reporter gene in skeletal muscle cells from a virus
      based vector: implications for diabetes treatment.

PMID- 8539985
TI  - In vitro advanced glycation end product formation in rat tail tendon fibers:
      influence of aminoguanidine.

PMID- 8539986
TI  - Fully integrated optical microscope system and computer workstation system for
      standardized islet cell measurements and analyses.

PMID- 8539987
TI  - Microencapsulation improves canine islet survival in vivo.

PMID- 8539988
TI  - Microencapsulation enhances canine islet survival during long-term culture.

PMID- 8539989
TI  - Use of confocal laser scanning microscopy for assessing islet viability.

PMID- 8539990
TI  - Preparation of pig pure islets without using density gradients.

PMID- 8539991
TI  - Soluble interleukin-2 receptor release during culture of human lymphocytes with
      human, porcine, or bovine islets and the effect of culture and cryopreservation.

PMID- 8539992
TI  - Preparation and long-term storage by culture or cryopreservation of purified
      bovine pancreatic islets.

PMID- 8539993
TI  - Large-scale isolation and functional characterization of bovine pancreatic
      islets.

PMID- 8539994
TI  - Xenotransplantation of a novel B-cell line (MIN6) in mesh-reinforced polyvinyl
      alcohol hydrogel bag.

PMID- 8539995
TI  - Mixed lymphocyte islet culture for assessment of immunoprotection by islet
      microencapsulation.

PMID- 8539996
TI  - Phenotypic transformation of isolated human islets in collagen matrix culture.

PMID- 8539997
TI  - An investigation into different approaches for minimizing microbial contamination
      of purified porcine islets.

PMID- 8539998
TI  - The intraductal administration of collagenase in University of Wisconsin solution
      at the time of harvesting significantly improves porcine islet isolation.

PMID- 8539999
TI  - Production of TNF alpha, IL-1, IL-6 and nitric oxide by isolated human islets.

PMID- 8540000
TI  - Immuno-histochemical and ultrastructural study of adult porcine pancreas during
      the different steps of islet isolation.

PMID- 8540001
TI  - Survival of allografted fetal pig pancreatic islet-like cell clusters [ICCs].

PMID- 8540002
TI  - Characterisation and origin of pig fetal islet-like cell clusters.

PMID- 8540003
TI  - The Diabetes Prevention Trial-Type 1 diabetes (DPT-1): implementation of
      screening and staging of relatives. DPT-1 Study Group.

PMID- 8540004
TI  - Stationary digestion after intraductal collagenase improves islet recovery in the
      rat.

PMID- 8540005
TI  - Decreased nitric oxide generation following human islet culture in serum-free
      media.

PMID- 8540006
TI  - Enhanced allograft acceptance by multiple infusions of donor bone marrow in
      humans.

PMID- 8540007
TI  - Long-term in vivo function of human mantled islets obtained by incomplete
      pancreatic dissociation and purification.

PMID- 8540008
TI  - Long-term culture of viable human pancreatic islets in pyruvate-rich medium.

PMID- 8540009
TI  - Functional evaluation of isolated islets from baboon pancreata.

PMID- 8540011
TI  - Cryopreservation of microencapsulated canine islets.

PMID- 8540010
TI  - Enhancement of donor cell chimerism in whole organ allograft recipients by
      adjuvant bone marrow transplantation.

PMID- 8540012
TI  - Tolerance induction to multiple donor rat islet allografts by intrathymic
      inoculation of spleen cell membrane antigens.

PMID- 8540013
TI  - Intrathymic tolerance and age.

PMID- 8540014
TI  - The INS B allele (1,428 Fok I) is associated with reduced IDDM incidence in
      autoantibody-positive first degree relatives despite the presence of
      autoantibodies and high-risk HLA alleles.

PMID- 8540015
TI  - Application of AN69 hydrogel to islet encapsulation: evaluation in the
      streptozotocin-induced diabetic rat model.

PMID- 8540016
TI  - Large-scale isolation of porcine pancreatic islets: significant improvement of
      the process.

PMID- 8540017
TI  - Streptozotocin-induced hyperglycemia in rats: analysis of complement activity
      after streptozotocin administration.

PMID- 8540018
TI  - Albumin improves islet isolation: specific versus nonspecific effects.
AB  - 1. BSA-containing solutions improve islet yields using standard collagenase
      digestion techniques. 2. The BSA effect on islet isolation is independent of
      source and lot of collagenase. 3. The BSA effect on islet isolation is not due
      solely to its colloid action, as HES failed to achieve the same level of
      improvement seen with albumin. 4. BSA can protect islets from warm ischemic
      injury, and the protective action appears to be unique to albumin, as HES was not
      as effective.

PMID- 8540019
TI  - Ultimate assessment of pig islet isolation by autotransplantation after
      pancreatectomy.

PMID- 8540020
TI  - A potential solution for the shortage of donors in islet transplantation using a
      novel oral antidiabetic agent, troglitazone.

PMID- 8540021
TI  - Immunogenicity of cryopreserved human islets.

PMID- 8540022
TI  - Enhanced expression of CD44 isoforms in nonobese diabetic (NOD) mice.

PMID- 8540023
TI  - Development of a cell line from the human fetal pancreas.

PMID- 8540024
TI  - Influence of gestational age on growth hormone-induced potentiation of insulin
      secretion from isolated human fetal islets.

PMID- 8540025
TI  - Dose dependence of bacillus Calmette-Guerin on the prevention of autoimmune
      diabetes in syngeneic islet transplantation.

PMID- 8540026
TI  - Expression of beta-galactosidase in mouse pancreatic islets by adenoviral
      mediated gene transfer.

PMID- 8540027
TI  - Effect of preservation conditions on human vertebral body marrow.

PMID- 8540028
TI  - Suitability of neonatal vertebral body marrow for transplant applications.

PMID- 8540029
TI  - A simple method for depletion of bone fragments from human vertebral body marrow.

PMID- 8540030
TI  - Automated processing of human vertebral body bone marrow yields preparations with
      stem cell content similar to that obtained with traditional manual preparation.

PMID- 8540031
TI  - Effect of depletion of class II bright cells on the immunogenicity and stem cell
      content of human vertebral body bone marrow.

PMID- 8540032
TI  - Rescue therapy with Tacrolimus (FK506) in renal transplant recipients--a
      multicenter analysis.

PMID- 8540033
TI  - Optimization of azathioprine therapy by measuring 6-thioguanine nucleotides and
      methylated mercaptopurine in renal allograft recipients.

PMID- 8540034
TI  - Neoral--a new microemulsion formula of cyclosporine A: interpatient
      pharmacokinetic variability in renal transplant recipients.

PMID- 8540035
TI  - Low-dose ATGAM treatment sufficiently reduces total T-cell counts and remains
      clinically effective in prophylactic and anti-rejection protocols.

PMID- 8540036
TI  - Decreased nephrotoxicity after the use of a microemulsion formulation of
      cyclosporine A compared to conventional solution.

PMID- 8540037
TI  - Three-day or ten-day ATG treatment for steroid-resistant rejection in kidney
      transplanted patients.

PMID- 8540038
TI  - A study to assess the efficacy, tolerability, and safety of a new oral
      formulation of Sandimmun--Sandimmun Neoral--in stable renal transplant patients.

PMID- 8540039
TI  - Clean intermittent catheterisation in kidney transplanted children with abnormal
      lower urinary tracts.

PMID- 8540041
TI  - Pediatric renal transplantation in the Nordic countries.

PMID- 8540040
TI  - Renal transplantation in children under 6 years of age.

PMID- 8540042
TI  - Magnesium deficiency after renal transplantation and cyclosporine treatment
      despite normal serum-magnesium detected by a modified magnesium-loading-test.

PMID- 8540043
TI  - Obesity and renal transplantation.

PMID- 8540044
TI  - Safe utilization and long-term follow-up of 368 marginal kidneys.
AB  - Three-hundred sixty-eight grafts of 1701 KTs performed during a 25-year period
      showed major anatomical anomalies: 358 kidneys presented an abnormal vascular
      supply, 8 organs had a double ureters, 2 were indivisible horseshoe kidneys. The
      outcome of these MKs is virtually identical (84%) to those obtained with
      transplant of normal grafts (85%). The advantages of ex vivo arterioplasty have
      been advocated.

PMID- 8540045
TI  - Pretransplantation plasmapheresis in HLA-sensitized patients: five years
      experience.

PMID- 8540046
TI  - Laparoscopic management of posttransplant pelvic lymphoceles.

PMID- 8540047
TI  - Outcome after transplantation of paired kidneys from the same cadaveric donors
      that were shared by two hospitals.

PMID- 8540048
TI  - Strong impact of HLA-DR-matching on graft survival in 413 consecutive cadaver
      kidney transplants performed in Copenhagen over an eight-year period.

PMID- 8540049
TI  - Organ sharing or local transplantation? Results of the kidney transplantation
      program in Bonn.

PMID- 8540050
TI  - Study of the effect of HLA-matched antigens shared between subsequent donors on
      the second kidney graft outcome.

PMID- 8540051
TI  - How safe is transplant nephrectomy? A retrospective study of 107 cases.

PMID- 8540052
TI  - Successful kidney transplantation after suppression of HLA alloantibodies with
      intravenous immunoglobulin in a highly sensitized patient.

PMID- 8540053
TI  - Calcium homeostasis after kidney transplantation: a prospective study.

PMID- 8540054
TI  - Immunoadsorption in acute vascular rejection after renal transplantation.

PMID- 8540055
TI  - EBV-induced post-transplant lymphoproliferative disorder (PTLD).

PMID- 8540056
TI  - Cytomegalovirus prophylaxis in antibody-treated renal transplanted patients.

PMID- 8540057
TI  - Neoral conversion study: shift from Sandimmune classic formulation to Sandimmune
      Neoral in heart and lung transplant patients.

PMID- 8540058
TI  - Avoidance of atrioventricular valve incompetence following orthotopic heart
      transplantation using direct bicaval anastomosis.

PMID- 8540059
TI  - Transplantation of a lobe of lung from mother to child following previous
      transplantation with maternal bone marrow.

PMID- 8540060
TI  - Double lung transplantation with bronchial artery revascularization using mammary
      artery.

PMID- 8540061
TI  - Lung transplantation in The Netherlands: first results of the medical technology
      assessment.

PMID- 8540062
TI  - Assessment of FEV1 fraction of the transplant and the native lung with 133Xe
      radiospirometry after single lung transplantation.

PMID- 8540063
TI  - Acute carpal tunnel syndrome immediately after combined kidney and pancreas
      transplantation.

PMID- 8540064
TI  - Persistent pancreatic fistula after pancreas transplantation treated with fibrin
      glue and octreotide.

PMID- 8540065
TI  - Experience with 150 pancreatic transplants.

PMID- 8540066
TI  - Hepatic malignancies, a controversial indication for liver replacement: 10 year
      experience from a Scandinavian center.

PMID- 8540067
TI  - Early postoperative renal dysfunction after adult liver transplantation.

PMID- 8540068
TI  - Central cardiovascular responses to surgical incision at a maximal mixed venous
      oxygen saturation.

PMID- 8540069
TI  - Effect of ursodeoxycholic acid treatment for cholestasis in liver transplant
      recipients.

PMID- 8540070
TI  - Sequential changes in serum and biliary bile acids after liver transplantation.

PMID- 8540071
TI  - Is an initial small-spectrum antibiotic regimen safe in fulminant hepatic
      failure?

PMID- 8540072
TI  - Central cardiovascular variables at a maximal mixed venous oxygen saturation in
      severe hepatic failure.

PMID- 8540073
TI  - Endothelin-1 in patients with fulminant hepatic failure: influence of high-volume
      plasmapheresis.

PMID- 8540074
TI  - Transcranial Doppler sonography may predict brain death in patients with
      fulminant hepatic failure.

PMID- 8540075
TI  - Percutaneous transhepatic cholangioscopic lithotripsy in liver transplant
      recipients.

PMID- 8540076
TI  - Cytomegalovirus DNA persists in various structures of liver allografts with
      chronic rejection.

PMID- 8540077
TI  - Combined use of fluconazole and selective digestive decontamination in the
      prevention of fungal infection after adult liver transplantation.

PMID- 8540078
TI  - Liver transplantation in acute liver failure can be as successful as in chronic
      liver disease.

PMID- 8540079
TI  - The Danish liver transplantation program and patients with serious acetaminophen
      intoxication.

PMID- 8540080
TI  - Organ donation: number of brain deaths, refusal rate, actual donation, and
      multiorgan transplantation 1990-1994 in a Danish population of 1 million compared
      to the whole of Denmark.

PMID- 8540081
TI  - Nordic collaboration in the supply of organs for transplantation.

PMID- 8540082
TI  - Reasons for non-acceptance of living kidney donors.

PMID- 8540083
TI  - Potential risk factors affecting delayed graft function after kidney
      transplantation.

PMID- 8540084
TI  - Less acute GVHD in patients receiving totally matched transplants from unrelated
      donors.

PMID- 8540085
TI  - Risk factors for septicemia during aplastic period after allogeneic bone marrow
      transplantation.

PMID- 8540086
TI  - Bone marrow transplantation for chronic myelogenous leukemia using unrelated
      donors: the experience at Huddinge Hospital.

PMID- 8540087
TI  - Cytokines in veno-occlusive disease of the liver after bone marrow
      transplantation.

PMID- 8540088
TI  - No beneficial effects, but severe side effects caused by recombinant human tissue
      plasminogen activator for treatment of hepatic veno-occlusive disease after
      allogeneic bone marrow transplantation.

PMID- 8540089
TI  - Intravenous immunoglobulin: immune modulatory effects in vitro and clinical
      effects in allogeneic bone marrow transplant recipients.

PMID- 8540090
TI  - Vitamin D analogues for immunosuppression: a comparison between various routes of
      administration.

PMID- 8540091
TI  - Additive immunosuppressive effect of combined mycophenolate mofetil and
      cyclosporin A in experimental rat cardiac transplantation.

PMID- 8540092
TI  - Inhibition of ATG-induced experimental transplantation tolerance with LS2616.

PMID- 8540093
TI  - Rat heart allograft survival after treatment with verapamil, captopril, and
      enalapril.

PMID- 8540095
TI  - Deoxyspergualin is synergistic with cyclosporin A, but not with FK506 in a rat
      heart allograft transplantation model.

PMID- 8540094
TI  - Suppression of immunoglobulin resynthesis after plasmapheresis: efficacy of
      various immunosuppressive drugs--a study in rats.

PMID- 8540096
TI  - Evidence that graft-versus-host reaction and rejection can occur simultaneously
      after allogeneic small-bowel transplantation.

PMID- 8540097
TI  - An experimental model of rat liver allograft rejection monitored with FNAB.

PMID- 8540098
TI  - Initial endothelial injury and cytomegalovirus infection accelerate the
      development of allograft arteriosclerosis.

PMID- 8540100
TI  - Study of CD11a/CD18 expression and mRNA synthesis in human polymorphonuclear
      cells.

PMID- 8540099
TI  - Experimental transplant arteriosclerosis: inhibition by angiopeptin and low
      molecular weight heparin derivatives.

PMID- 8540101
TI  - Ultrasound and fine-needle aspiration biopsy in the monitoring of rat kidney
      allografts.

PMID- 8540102
TI  - Ex vivo model for xenotransplantation.

PMID- 8540103
TI  - Expression and function of human CD59 and human CD55 in transgenic mice.

PMID- 8540104
TI  - Expression of functional decay-accelerating factor in transgenic mice.

PMID- 8540105
TI  - The effect of a depleting anti-CD4 monoclonal antibody on T cells and fetal pig
      islet xenograft survival in various strains of mice.

PMID- 8540106
TI  - Fetal pig xenografts in NOD/Lt mice: lack of expression of Gal(alpha 1-3)Gal on
      endocrine cells and the effect of peritransplant anti-CD4 monoclonal antibody and
      graft immunomodification on graft survival.

PMID- 8540107
TI  - Role of IL-4 in pig proislet xenograft rejection in mice.

PMID- 8540108
TI  - Metabolic aspects of cultured hepatocytes for use in a bioartificial liver
      support system.

PMID- 8540109
TI  - Lazaroid U74500A enhances donor lung preservation in the rat transplant model.

PMID- 8540110
TI  - Strong tolerance mediated by allografting in the rat is due to donor liver
      leukocytes.

PMID- 8540111
TI  - High frequency of alloreactive T cells is a consequence of the presentation of
      many peptides by allogeneic MHC molecules.

PMID- 8540112
TI  - Chronic rejection after small-bowel transplantation.

PMID- 8540114
TI  - HCMV-induced chorioretinitis in the rabbit.

PMID- 8540113
TI  - Upregulated cytokine expression in chronic renal allograft rejection.

PMID- 8540115
TI  - Comparing two modalities of screening for prostate cancer: digital rectal
      examination + transrectal ultrasonography vs. prostate-specific antigen.
AB  - AIMS AND BACKGROUND: To evaluate the performance and feasibility of screening for
      prostate cancer by comparing screening modalities. METHODS: Prospective study of
      two comparable cohorts of healthy resident males aged 60 to 75 years. Screening
      attenders in the two invited cohorts were screened either by digital rectal
      examination (DRE) and transrectal ultrasonography (TRUS), or by serum prostate
      specific antigen determination (PSA: cutoff 4 ng/ml). Attendance and biopsy
      rates, predictive values, prevalence of screen-detected cancers, as well as
      screening costs were determined, and the efficiency of the two screening
      modalities was compared. RESULTS: 1425 subjects were screened by DRE+TRUS.
      Attendance rate was 33.7%, the biopsy rate was 2.7%, and the prevalence of
      detected cancers was 1.82%. A total of 1315 subjects was screened by PSA.
      Attendance rate was 66.9%, the biopsy rate was 2.8%, and the prevalence of
      detected cancers was 1.67%. Screen-detected cancer stage was more favorable than
      observed in clinical practice, and early detection was evident, with the
      prevalence/incidence ratio higher than 10:1 in both programs. The cost per
      subject screened was about 34,000 Lire for DRE+TRSU and about 30,000 Lire for PSA
      program. CONCLUSIONS: The study confirms that early detection of prostate cancer
      is possible and that screening is practically feasible. Both screening modalities
      achieved comparable results as regards early detection, but screening by PSA had
      a higher compliance and lower costs. PSA seems the ideal test to be used in
      prospective controlled studies aimed at demonstrating screening efficacy.

PMID- 8540116
TI  - Colorectal cancer in young adults.
AB  - The study was carried out to promote a greater awareness of the potential for
      colorectal cancer in young adults under 40 years of age. During the 8 years
      between 1986 and 1993, 237 patients with adenocarcinoma of the colon and rectum
      were operated at the Uludag University Hospital. Of these 237 cases, 46 patients
      under 40 years old were reviewed retrospectively. They accounted for 19.4% of the
      total number of patients with carcinoma of the colon and rectum operated during
      the same period. Rectal bleeding was the most common presenting symptom. The mean
      duration of time from the onset of symptoms to diagnosis was 5.8 months. The
      rectosigmoid area was the most frequently involved site (80%). Seventy-six
      percent of the patients had Dukes' stage C or D tumors. Forty-eight percent of
      the tumors were either poorly differentiated or mucinous. The cumulative survival
      rate at 5 years was 43.4%. Patients under 40 years old with carcinoma of the
      colon and rectum are usually symptomatic and have advanced disease at the time of
      presentation. Although colorectal cancer is usually a disease of older patients
      it is becoming more common in younger populations.

PMID- 8540117
TI  - Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight
      patients with primary tonsillary lymphoma.
AB  - AIMS: To analyze the clinical and therapeutic aspects of patients with primary
      tonsillary non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with primary
      tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology
      Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients
      were male, 13 were female. Median age was 55 years. RESULTS: Constitutional
      symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor
      classification were I and II in 12 and 16 patients, respectively. According to
      the Rappaport classification, poorly differentiated lymphocytic was the most
      common pathologic subgroup (42.9%). Grades according to the Working Formulation
      were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two
      patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone
      (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were
      the regimens most commonly employed. Eighteen patients received radiotherapy to
      Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy
      plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with
      radiotherapy alone. In addition to the 20 patients who achieved complete
      remission, 3 patients achieved partial remission; the overall response rate was
      82.1%. The response rates and survival attained with the combined modality,
      chemotherapy, or radiotherapy alone were not statistically different (P > 0.05).
      The median follow-up was 14 months. Overall and disease-free survival at 5 years
      were 62.6% and 77.6%, respectively. Pathologic grade was the most important
      prognostic factor influencing overall survival in the Cox multivariate model.
      CONCLUSIONS: Poorly differentiated lymphocytic lymphomas were the most common
      pathologic subtype, and pathologic grade was the most important prognostic factor
      to influence survival in the present study. Although combined modality treatment
      did not appear to be superior to chemotherapy or radiotherapy alone, a larger
      number of patients is needed to draw definite conclusions.

PMID- 8540118
TI  - Combined carboplatin and cytosine arabinoside in metastatic melanoma refractory
      to dacarbazine.
AB  - This is a preliminary report on the efficacy and toxicity of the combination
      chemotherapy regimen with carboplatin and cytosine arabinoside in dacarbazine
      resistant metastatic melanoma. Patients were considered eligible in the presence
      of measurable disease sites, an ECOG performance status of 2 or less, a life
      expectancy of at least 2 months, and prior dacarbazine treatment. The planned
      schedule consisted of cytosine arabinoside (150 mg/m2 intravenously plus 50 mg
      subcutaneously), followed by a rapid infusion of carboplatin (350 mg/m2 on day
      1). Courses were administered every 3 weeks according to hematologic recovery.
      Twenty-one consecutive patients were evaluable for activity and toxicity, the
      response rate was 19% (95% confidence interval, 5-42%). There was no complete
      remission. Toxicity was tolerable being myelosuppression the main side effect. In
      conclusion, the combination of carboplatin and cytosine arabinoside has limited
      activity as a salvage treatment in melanoma patients failing on dacarbazine
      chemotherapy. Moreover, the regimen is well tolerated and easy to administer in
      an outpatient setting.

PMID- 8540119
TI  - Cisplatin and VP16 in metastatic breast carcinoma as a third-line chemotherapy: a
      randomized study comparing low versus high doses of cisplatin.
AB  - AIMS AND BACKGROUND: The study was designed to define the activity of the
      combination of cisplatin and etoposide as third-line chemotherapy for advanced
      breast cancer and to investigate the role of the dosage of cisplatin on the
      effectiveness of the combination. METHODS: Ninety-five eligible patients with
      advanced breast cancer who had failed or relapsed on two previous lines of
      chemotherapy were randomized to receive cisplatin at a high dose (100 mg/m2 i.v.
      day 1, arm A) or a low dose (60 mg/m2 day 1, arm B), combined with etoposide (100
      mg/m2 i.v. days 4, 6 and 8). Cycles were repeated every 3 weeks. RESULTS: Of the
      78 patients evaluable for response (39 in arm A and 39 in arm B), 9 (12%) showed
      complete or partial response, 5 (13%) in the high-dose arm and 4 (10%) in the low
      dose arm. One complete response was seen in the high-dose arm and none in the low
      dose arm. The only 2 patients with brain involvement showed an objective response
      (one CR in arm A and one PR in arm B). Median time to progression was 14 weeks in
      arm A and 10 weeks in arm B, median duration of remission 28 and 34 weeks, and
      survival 36 and 35 weeks, respectively. The differences were not significant. As
      expected, the patients in the high-dose arm experienced more severe toxicity. One
      toxic death was observed in each arm due to sepsis in agranulocytosis. The
      difference was statistically significant regarding nausea and vomiting.
      Neurotoxicity and ototoxicity were not relevant problems in this patient setting.
      CONCLUSIONS: Considering the very poor prognostic factors presented by these
      patients, the combination showed a certain activity, and further evaluation in
      earlier stages of disease is warranted. A particular responsiveness on brain
      metastases is suggested. The dose of cisplatin was not proven to be of
      significant importance.

PMID- 8540120
TI  - Alpha interferon as initial treatment of essential thrombocythemia. Analysis
      after two years of follow-up.
AB  - AIMS AND BACKGROUND: Recombinant alpha-interferon has been shown to be effective
      in essential thrombocythemia and in thrombocytosis associated with other
      myeloproliferative disorders. PATIENTS AND METHODS: Twenty-five untreated
      patients were enrolled in our study from May 1989 to April 1992. Recombinant
      alpha interferon-2b was administered at an initial dose of 2 megaunits (MU)/m2
      three times a week at escalating doses to 5 MU/m2 or the maximum tolerated dose.
      The mean follow-up for patients still in treatment at the time of this report was
      35.9 months (range, 24-63). RESULTS: Fourteen patients (56%) had achieved a
      complete remission by a mean time of 152 days; 6 patients (24%) had achieved a
      good partial remission by a mean of 180 days. In addition to the favorable effect
      on platelet count, a marked improvement in clinical symptoms was observed.
      Treatment had to be discontinued in 9 patients (36%), 5 for toxicity (3
      neurologic, 1 anemia and 1 severe hypertriglyceridemia) at a median of 155 days
      from the beginning of therapy (range, 30-400). Four patients refused to continue
      therapy because of low tolerance (flu-like syndrome) at mean of 160 days from the
      beginning of therapy (range, 34-301). CONCLUSIONS: In our study, lower doses were
      administered compared with previous short-time trials. The present data show that
      interferon is an effective alternative to cytostatic agents in long-term
      treatment of patients with essential thrombocythemia, even when used at lower
      dosages.

PMID- 8540121
TI  - Hairy cell leukemia: an ultrastructural study of hairy cells before and after
      interferon therapy.
AB  - AIMS AND BACKGROUND: To test the diagnostic relevance of the presence of ribosome
      lamellae complexes (RLC) in 18 hairy cell leukemia (HCL) cases, and to correlate
      clinical response to interferon (IFN) therapy with hairy cell ultrastructural
      modifications in 5 of these cases. METHODS: Peripheral blood samples of 18 HCL
      patients were studied by transmission electron microscopy. Five of these patients
      received IFN treatment and subsequently were evaluated at different intervals for
      ultrastructural modifications of the peripheral blood. RESULTS: RLC were observed
      in 66.66% of our 18 HCL patients, but in less than 1% of all the cases contained
      in the files (consisting of over 8,000 cases) of our Electron Microscopy Unit.
      The microvilli disappeared after IFN therapy in the patients who did not display
      RLC before therapy (2 cases), whereas they were fewer, shortened and blunted, but
      still evident, in the cases where RLC had been observed before therapy (3 cases).
      Moreover, in the HCL cases with pretherapy RLC, neoplastic cells still
      synthesized RLC after IFN treatment, but their morphologic aspect was immature.
      CONCLUSIONS: Our study suggests that: 1) the presence of RLC, when associated to
      the hairy aspect of the cells, has considerable diagnostic value even though RLC
      are observed in other rare neoplastic and non-neoplastic conditions; 2) HCL cases
      with pre-therapy RLC exhibited a morphologic response to IFN therapy different
      from that of cases without pre-therapy RLC; 3) the quantitative and qualitative
      modifications of RLC following IFN treatment, as yet unexplained, are probably
      related to IFN action, in line with a previous report.

PMID- 8540122
TI  - Endometrial stage I carcinoma treated with surgery and adjuvant irradiation: a
      retrospective analysis.
AB  - AIMS AND BACKGROUND: Data from the literature show that the incidence of pelvic
      recurrences in poor prognosis endometrial carcinoma is significantly reduced by
      combined surgery and radiotherapy compared to surgery alone. METHODS: In this
      paper we analyze the results of the combined treatment surgery and adjuvant
      irradiation in patients with endometrial carcinoma with regard to survival, site
      of progression, and toxicity. The surgical treatment consisted of total abdominal
      hysterectomy and bilateral salpingo-oophorectomy in 40 patients. Pelvic and para
      aortic node dissection was performed in 19 patients and lymph node sampling in 5.
      RESULTS: Overall 5-year survival was 85%. One patient had local failure, and 5
      patients with local control of disease had distant metastases. Toxicity was mild
      and transient. CONCLUSIONS: Our experience confirms the data of the literature.
      Postoperative irradiation is a safe and well-tolerated treatment that can achieve
      a good local control in high risk, stage I, endometrial carcinoma. The control of
      distant metastases remains an open question.

PMID- 8540123
TI  - Clinical efficacy of cancer subcutaneous immunotherapy with interleukin-2 in
      relation to the pretreatment levels of tumor growth factor insulin-like growth
      factor-1.
AB  - AIMS AND BACKGROUND: IGF-1 has been proven to be one of the most important growth
      factors for normal and neoplastic cells. Abnormally high levels of IGF-1 have
      been observed in cancer patients. Since it has been demonstrated that some growth
      factors may counteract the action of antitumor cytokines, the presence of
      increased IGF-1 concentrations could reduce the efficacy of cancer biotherapies
      with cytokines, such as IL-2. The present study was performed to evaluate the
      efficacy of IL-2 immunotherapy in relation to the pretreatment levels of IGF-1 in
      advanced cancer patients. METHODS: The study included 20 consecutive patients
      with metastatic renal cell cancer who were treated subcutaneously with IL-2 at 6
      million IU/day for 5 days/week for 6 weeks. IGF-1 serum levels were measured by
      RIA on venous blood samples collected before the immunotherapy, after 3 weeks,
      and at the end of IL-2 injection. RESULTS: Objective tumor regressions were
      obtained in 5/20 patients, consisting of 1 complete response (CR) and 4 partial
      responses (PR). Nine patients had stable disease and the last 6 patients
      progressed. Abnormally high pretreatment levels of IGF-1 were seen in 13/20
      patients. The percent of clinical responses (CR + PR) was significantly higher in
      patients with normal pretreatment concentrations of IGF-1 than in those with
      elevated levels (4/7 vs 1/13, P < 0.01). No significant changes in mean IGF-1
      levels occurred during IL-2 therapy. However, mean IGF-1 levels increased in
      progressing patients and decreased in those with a response or stable disease,
      even though none of the differences was statistically significant. CONCLUSIONS:
      The study showed that high pretreatment levels of IGF-1 are associated with a
      reduced efficacy of IL-2 immunotherapy of renal cancer. Further studies are
      required to establish whether IGF-1 levels simply reflect the extension of
      disease, or whether they may influence per se the action of IL-2.

PMID- 8540124
TI  - Long-term relapses in breast cancer patients (estrogen receptor status).
AB  - To investigate the relation between estrogen receptor (ER) status and timing of
      relapse, we retrospectively studied two groups of patients (200 cases in each
      group) who underwent radical mastectomy and developed an early relapse (within 3
      years of the surgery) or a long-term relapse (more than 8 years after surgery).
      One-hundred and eighty-two (91%) patients who developed a long-term relapse were
      ER-positive (ER+), whereas only 64% of patients who developed an early relapse
      were ER+ (P < 0.001), supporting the hypothesis that a long-term relapse is more
      frequently associated with an ER+ tumor. A review of the literature, which
      indicated that a long-term relapse arises more frequently in patients in whom a
      partial hormone control is maintained, seems to support this finding, albeit the
      presence of 18 ER-negative (ER-) cases in our study. However, this apparent
      contradictory observation could be explained by the fact that 12 of our patients
      were in premenopause and that ER-status could have been false ER- results due to
      the binding of endogenous estradiol to ER.

PMID- 8540125
TI  - Spontaneous mutation of cell oncogenes plays a minor role in neoplastic
      transformation of virus-induced murine T-cell lymphomas.
AB  - Mink cell focus-forming viruses (MCF) are slow-transforming retroviruses that are
      able to accelerate the appearance of T-cell lymphomas when injected in newborn
      AKR mice. Activation of proto-oncogenes by proviral insertion is thought to be
      the major mechanism by which these viruses exert their oncogenic potential.
      However, molecular phenomena not strictly virus-determined, such as mutations in
      cellular oncogenes/tumor suppressor genes or chromosome aberrations, have been
      hypothesized to contribute to the achievement of the fully neoplastic phenotype
      in MCF-infected mice. To evaluate the role of spontaneous mutagenesis phenomena
      in murine virus-induced lymphomagenesis, we analyzed a series of 18 MCF247
      induced thymic lymphomas and derived cell lines for the presence of p53 and c-ras
      gene mutations. Only 1 mutation at the p53 gene and 1 mutation at the ki-ras gene
      were detected in our study. Our results suggest that spontaneous mutagenesis
      plays a minor role in virus-induced lymphomagenesis and support the notion that
      multiple proviral insertions could be the prevalent mechanism of transformation
      in this experimental system.

PMID- 8540126
TI  - Proliferating cell nuclear antigen immunoreaction in adrenal tumors.
AB  - AIMS AND BACKGROUND: We studied, retrospectively, 33 cases of adrenal tumors of
      children at the Pediatric Endocrinology Unit, Children's Institute, Sao Paulo
      State University Medical School, from 1975 to 1993. All patients had at least 2
      years of follow-up with a few exceptions. METHODS: Clinical follow-up data were
      correlated with histopathologic review, laboratory data and cell kinetic
      evaluation (based on detection of proliferating cell nuclear antigens). RESULTS:
      With one exception, all the patients had presented signs of androgen production
      and had high levels of dehydro-epiandrosterone-sulfate. Tumor weight evaluation
      represented a good parameter of neoplasm evolution: of 19 cases weighing less
      than 250 g, 17 had no evidence of disease after surgery, and 2 had an unfavorable
      prognosis. Of 14 cases weighing more than 250 g, only 1 had no evidence of
      disease and 13 had an unfavorable evolution. CONCLUSIONS: Proliferating cell
      nuclear antigen (PCNA) was not helpful to evaluate adrenal neoplasm evolution:
      our study did not show any correlation between PCNA score and prognosis.

PMID- 8540127
TI  - Comparative in vitro and in vivo study of a nitroxyl derivative of 5-fluorouracil
      (magnizil) on human gastrointestinal tumors.
AB  - AIMS AND BACKGROUND: There is much interest in nitroxyl derivatives of cytotoxic
      agents. We evaluated the potential activity of magnizil, a derivative of 5
      fluorouracil, on human gastrointestinal tumors in 3 different in vitro and in
      vivo experimental models. METHODS: The activities of magnizil and 5-fluorouracil
      were comparatively determined in vitro on the HT29 cell line by a clonogenic
      assay and on tumor clinical specimens by an antimetabolic assay. The activity of
      both the drugs against human tumors was also assessed in mice with the subrenal
      capsule assay. RESULTS: A similar cytotoxic activity was found for magnizil and 5
      fluorouracil on the HT29 cell line. As regards human tumors, a lower activity was
      observed for the nitroxyl derivative than for 5-fluorouracil, with response rates
      of 25% and 50%, respectively, at comparable concentrations. Moreover, among the
      tumors transplanted in the subrenal capsule of mice, two were sensitive to
      magnizil and 3 to 5-fluorouracil. CONCLUSIONS: Even though experimental results
      on human tumors indicate a somewhat lower activity for magnizil than the parent
      compound, its low toxicity and the possibility to clinically use high doses
      suggest the opportunity to further investigate the potential of this new
      anticancer agent on larger series of colorectal cancers in experimental systems.

PMID- 8540128
TI  - Unusual ultrastructural findings in giant-cell fibroblastoma.
AB  - We report on a 4-year-old boy with recurrent giant-cell fibroblastoma of the
      right nasal genal region. Histologic examination revealed that both lesions were
      constituted of spindle and stellate cells and a minor amount of multinucleated
      giant cells in a myxoid stroma containing cisternal-like spaces.
      Immunohistochemical examination revealed positivity for vimentin in both cellular
      components. Ultrastructural examination showed, in some spindle and
      multinucleated cells, two kinds of intracellular crystalline inclusions, located,
      respectively, in the cisternae of the rough endoplasmic reticulum and, apparently
      free, in the cytoplasm. To the best of our knowledge, this case, unusual for its
      location, is the first example of giant-cell fibroblastoma bearing intracellular
      crystalline inclusions.

PMID- 8540129
TI  - Iatrogenic pneumocephalus in a man with undifferentiated nasopharyngeal
      carcinoma. A case report.
AB  - A case of pneumocephalus in a 45-year-old male with undifferentiated
      rhinopharyngeal carcinoma is described. The patient was initially subjected to
      radiotherapy and then to transmaxillary resection and a second course of
      stereotactic radiotherapy for recurrent disease. Lastly, the patient was treated
      with chemotherapy because of local-regional disease progression. After two cycles
      of cisplatin, adriablastine and bleomycin, the patient suddenly entered in coma.
      Cerebral CT scan evidenced the presence of air in the frontal and lateral cornua,
      in the subarachnoid space of the base cisternae extending to the 7th cervical
      vertebra. After 8 months of a clinical stationary condition, the patient died.
      The various treatments used are critically reviewed, and modern therapeutic
      approaches for the neoplasm and the toxicity involved are discussed. We conclude
      that in nasopharyngeal carcinoma, for patients who relapse after radiotherapy,
      successive local-regional therapies (surgery, re-irradiation) should be carefully
      evaluated to avoid demolishing treatments, which are burdened with severe side
      effects that might influence the quality of life with only slight improvement of
      overall survival. Furthermore, the presence of persistant aqueous rhinorrhea in
      these patients should be carefully evaluated, because it could be an early
      symptom of a cerebrospinal fluid leak.

PMID- 8540130
TI  - Follicular thyroid carcinoma with a predominant insular component in a child: a
      case report.
AB  - Thyroid carcinoma is rare in children and differs from its adult counterpart in
      many aspects, including that childhood thyroid carcinomas are all well
      differentiated. Here we present a 14-year-old female from a goitrous area with
      follicular thyroid carcinoma with a predominant insular component. The child was
      well without recurrence or metastases after 5 years of follow-up.

PMID- 8540131
TI  - Acute myeloblastic leukemia associated with mediastinal nonseminomatous germ cell
      tumors. Report on two cases.
AB  - The demonstrated association with hematologic neoplasms may partially account for
      the poor survival of patients with mediastinal nonseminomatous germ cell tumors
      (MNSGCT) compared to patients with testicular and retroperitoneal counterparts.
      It has been shown that the median interval from the diagnosis of MNSGCT to the
      diagnosis of the hematologic disorders is 6 months, which contrasts sharply with
      the average time of 2 to 3 years for the development of therapy-related
      leukemias. The 2 cases herein described, 1 male and 1 female, developed acute M2
      leukemia 4 and 2 years after the diagnosis of MNSGCT. In the second patient (the
      first female ever described), we cannot exclude a pathogenetic role of the PEB
      regimen (platinum, etoposide, bleomicin), even though the total dose of etoposide
      administered has been demonstrated to have a mild leukemogenic potential. This is
      not the case of the first patient, who did not receive adjuvant chemotherapy
      after the radical resection of primary MNGSCT and developed the hematologic
      disorder a few months after local recurrence. In conclusion, the time elapsed
      from chemotherapy administration does not discriminate the hematologic neoplasms
      associated to MNGSCT from those related to therapy.

PMID- 8540133
TI  - [Sequelae of laparoscopic sterilization].

PMID- 8540134
TI  - [Laparoscopic sterilization. Late complications of the endocoagulation method].
AB  - The objective of this analysis was to assess the failure rate and incidence of
      regret of tubal sterilization performed by the endocoagulation technique. The
      design was a register-based retrospective study. A total of 585 sterilizations
      were performed from January 1986 to December 1992 in the county hospital of
      Sonderborg. The patients who had undergone sterilization were identified by
      diagnosis from the database of "Kommune-data". Forty patients were excluded due
      to different reasons. The frequency of hospitalization from the operation to July
      94 was registered. The actual case records were examined. The failure rate
      following endocoagulation was 0.92% (one intrauterine and four extrauterine
      pregnancies) corresponding to an incidence of 1.77/1000 women/year. Two women
      (0.37%) developed hydrosalpinx after the operation. Ten patients (1.8%) wanted a
      reversal of sterilization. It was concluded, that tubal sterilization by the
      endocoagulation method is cheap and safe. The failure rate is similar to that of
      other methods. Implantation in the peritoneal space is avoided. Thermic
      destruction is minimized, and the risk of peroperative burning of the tissue is
      therefore reduced.

PMID- 8540132
TI  - Vimentin, AgNORs and estrogen-receptor-related protein-29 in breast carcinoma.

PMID- 8540135
TI  - [Is smoking during pregnancy a cause of premature delivery?].
AB  - Preterm birth is an important determinant of perinatal mortality and morbidity.
      During the last ten years the rate of preterm birth has remained unchanged, and
      even though advances in neonatal intensive care have improved the chances of
      survival of the preterm child, the mortality remains high. In most cases the
      etiology is unknown, but several factors have been associated with preterm birth.
      However, most of these factors are not accessible for prevention. The search for
      preventable causes of preterm birth is therefore important. We reviewed English
      publications concerning smoking during pregnancy and preterm birth. We conclude
      that smokers have about a 50% higher risk of preterm birth compared to non
      smokers. Furthermore, a dose response relationship seems to be present; the more
      the pregnant women smoke the higher the risk of preterm birth. If all pregnant
      women stopped smoking it can be estimated that between 5% and 20% of all preterm
      births could be avoided.

PMID- 8540136
TI  - [Desmopressin in the treatment of hemorrhagic diathesis].
AB  - Over the past several years, the use of 1-deamino-8-D-arginine vasopressin
      (DDAVP), a synthetic analogue of vasopressin, has been found to be useful in the
      treatment of patients with abnormal bleeding tendency. This article is a review
      of inherited and acquired disorders with prolonged bleeding time in which DDAVP
      is supposed to shorten the bleeding time. DDAVP is established as effective
      therapy of the abnormal haemostasis in mild or moderate haemophilia A and von
      Willebrand's disease. Frequently, DDAVP infusions are used to control bleeding in
      patients with uraemia. Bleeding time is also significantly shortened in patients
      with liver cirrhosis, although randomized trials of DDAVP therapy of
      gastrointestinal bleeding in this group of patients are still needed. Shortening
      or normalization of the bleeding time with DDAVP has also been observed in
      patients with inherited platelet dysfunctions, acquired disorders of haemostasis
      and abnormal haemostasis in chronic myeloproliferative diseases. In addition,
      preoperative treatment with DDAVP seems to reduce blood loss during surgery.

PMID- 8540137
TI  - [Mortality among victims of traffic accidents with multiple injuries. A
      descriptive study 1986-1990].
AB  - In the period 1986-1990, 16,307 patients were injured in road traffic accidents
      in the city of Odense, Denmark. 251 had multiple injuries according to the
      definition: AIS > or = 3 in at least two body regions. Overall mortality was 41%,
      while the mortality in hospital was 20%. 19 patients died within the first 24
      hours after admission mainly due to brain damage, while 18 patients died later
      than 24 hours mainly from complications. These patients also had a higher average
      age (55 years) than the rest (34 years). The median Injury Sverity Score (ISS)
      was 26 for the whole series, and 19 for survivors. Median ISS was 59 for patients
      who were dead on arrival, whereafter it fell to 43 for patients who died within
      the first 24 hours after admission, with a further decrease to 29 for patients
      who died after 24 hours. 50% of all serious injuries were located in the thorax,
      27% in the brain and 22% in the abdomen. The litterature on the subject is
      reviewed.

PMID- 8540139
TI  - [Surgical treatment of carotid-cavernous fistulas. A description of open surgical
      techniques in the treatment of carotid-cavernous fistula with preserved normal
      flow in the internal carotid artery].
AB  - We have used a packing technique for surgical treatment of carotico-cavernous
      fistulas, which allows preservation of the flow in the internal carotid artery.
      We have treated six patients for carotico-cavernous fistulas with this technique,
      and in all patients the preoperative symptoms and signs disappeared completely.
      One patient still had a slight paresis of the left abducent nerve due to the
      operation three months after the operation. Surgical treatment of carotico
      cavernous fistulas is effective and probably preserves the flow in the internal
      carotid artery.

PMID- 8540138
TI  - [Perioperative risk in heart surgery. An original material and review of
      difficulties in correct comparisons with other materials].
AB  - The purpose of this study was to present data concerning morbidity and mortality
      after cardiac surgery and to establish a method to make the presentation
      comparable to other reports. The main difficulty in comparing results of surgery
      of one institution with those of another is the lack of a simple and widely
      acceptable quantification of risk. A preoperative risk classification of patients
      requires readily available and objective data. The shortage of standardized
      criteria for comparing outcome was obvious as only a few comprehensive reports
      regarding preoperative predictors were found in the literature. The method of
      Tuman et al is based on 12 preoperative risk factors that are reasonably free of
      observer bias and practically obtainable. This method was used to report the
      results of 628 consecutive patients undergoing coronary revascularization or
      valvular surgery. Total in-hospital morbidity was 3.5% and mortality 1.0%. The
      most important predictors for postoperative morbidity were valvular surgery,
      advanced age, renal dysfunction, recent myocardial infarction and pulmonary
      hypertension. The system is most useful in predicting good outcome in low-risk
      patients. The identification of high-risk patients is valuable in spite of the
      limited predictive ability, by allowing special attention to be directed to the
      patient at risk.

PMID- 8540140
TI  - [Extensive rectal cancer--preserved intestinal and urinary continence after en
      block rectal resection and radical cystectomy].
AB  - A patient with rectal cancer and invasion of the urinary bladder without extra
      pelvic spread underwent total pelvic exenteration with rectal resection and
      bladder substitution with the urethro-ileal Kock reservoir. The patient has
      normal bowel and voiding functions and is without recurrence after two years.

PMID- 8540141
TI  - [Fluid retention in cirrhosis].

PMID- 8540142
TI  - [Paracetamol poisoning].

PMID- 8540143
TI  - [Ketamine and phantom pain].

PMID- 8540144
TI  - [A 35-year-old woman referred for hypoglycemia].

PMID- 8540145
TI  - [Topical corticosteroids].

PMID- 8540146
TI  - [Topical capsaicin and joint pain: a therapeutic break-through?].

PMID- 8540147
TI  - [Hypotension during anesthesia induction in a young patient].

PMID- 8540148
TI  - [Verlaine: long sobs on Normandy].

PMID- 8540149
TI  - [Gastroesophageal reflux (round table I)].

PMID- 8540150
TI  - [Gastroesophageal reflux (round table II)].

PMID- 8540151
TI  - [Anicteric cholestasis in a 75-year-old man].

PMID- 8540152
TI  - [What is becoming of psychosomatic medicine? From psychogenesis to
      psychopharmacology].

PMID- 8540153
TI  - Relationship of the structure of ureteral muscularis to in vitro spontaneous
      contractions.
AB  - We investigated the anatomical structure of the smooth muscle layers of the mid
      portion of the canine ureter. In transverse sections the inner muscle bundles
      appear to be oriented longitudinally and the outer muscle bundles appear to be
      oriented in a circular configuration. In sections cut parallel with the
      longitudinal axis of the ureter, the inner and outer bundles appear to be oblique
      and are oriented in a mesh-line manner. In oblique sections, cut parallel with
      the helically oriented ureteral muscle, bundles appear to be oriented in a
      lengthwise configuration. These anatomical studies show that canine ureteral
      smooth muscle is composed of spiral fibers in a mesh structure and that helical
      muscle strips which include a significant percentage of continuous bundles have a
      greater capacity to generate spontaneous contractions in vitro than do transverse
      and longitudinal muscle strips.

PMID- 8540154
TI  - Clinicopathological study on upper urinary tract tumors and associated bladder
      tumors.
AB  - We reviewed 82 patients with 83 upper urinary tract tumors and investigated those
      who had associated bladder tumors. Of these patients, 7 (9%) had previous bladder
      tumors, 14 (17%) had concurrent bladder tumors, and 18 (22%) subsequently
      developed bladder tumors. As 1 patient subsequently developed a bladder and a
      upper urinary tract tumor at different times, 38 patients (46%) had associated
      bladder tumors. The time interval between the occurrence of a previous bladder
      tumor and the subsequent upper urinary tract tumor was 11 to 144 months (mean: 41
      months), while that between an upper urinary tract tumor and the subsequent
      bladder tumor was 3-31 months (mean: 12 months). Most of the previous bladder
      tumors were papillary, multiple, and noninvasive (pT1 or less). Multiple upper
      urinary tract tumors were associated with a high incidence of concurrent bladder
      tumors, while high-grade (G2, G3) or invasive (pT2 or more) upper urinary tract
      tumors were associated with a high incidence of concurrent and subsequent bladder
      tumors. Patients with concurrent bladder tumors had a worse prognosis than those
      with previous or subsequent bladder tumors due to the increased incidence of high
      stage tumors at either the upper tract or bladder site. Our findings suggest that
      tumor cell implantation is a possible mechanism for the recurrence of bladder
      tumors and upper urinary tract tumors.

PMID- 8540155
TI  - Clinical implication of neuroendocrine differentiation in prostatic
      adenocarcinomas.
AB  - Specimens from 75 cases of prostatic adenocarcinoma of different M.D. Anderson
      degrees of malignancy were stained immunohistochemically for neuron-specific
      enolase (NSE), prostatic specific antigen (PSA) and prostatic acid phosphatase
      (PAP). None of these tumors presented on hematoxylineosin sections any features
      suggesting neuroendocrine differentiation; nevertheless, 18.7% of the tumors were
      at least focally NSE positive. Because of the synchronous antigenic expression of
      the NSE-positive cells to PSA and PAP, the authors suggest that prostatic
      exocrine and neuroendocrine cells derive from a common precursor stem cell. The
      possibility of a more aggressive biological behavior of these tumors in
      comparison to the conventional carcinomas is discussed. The probable clinical
      necessity for a combined therapeutic approach is also investigated.

PMID- 8540156
TI  - Intraoperative irradiation: another option for the treatment of > or = 3 cm
      residual mass following chemotherapy for advanced testicular seminoma.
AB  - Four patients with advanced testicular seminoma and > or = 3 cm postchemotherapy
      residual retroperitoneal masses underwent retroperitoneal lymph node dissection
      (RPLND) followed by intraoperative irradiation (IORT) to a dose of 20 Gy. The
      RPLND was incomplete in all cases and hence all patients received IORT. Two
      patients showed viable carcinoma in the resected specimen and were administered
      additional chemotherapy. There were no complications of IORT (bowel, ureteric,
      haematologic, neurogenic). All patients are alive and disease-free at a mean
      follow-up period of 19 months (range 10-26). IORT is an attractive treatment
      alternative in this situation. Further, this approach also identifies patients
      with viable carcinoma, who are candidates for additional chemotherapy.

PMID- 8540157
TI  - Epididymo-orchitis as a complication of brucellosis.
AB  - A study of 84 patients who were diagnosed with epididymo-orchitis between July
      1987 and September 1993 is presented. Brucellosis was a complication in 14 cases
      (17%). All 14 cases had elevated agglutination titers. Brucella blood culture was
      found to be positive in 4 of 14 cases (28.5%). Standard therapy regime
      (streptomycin plus tetracycline) was effective in 13 of 14 (93%) cases.

PMID- 8540158
TI  - Value of color Doppler sonography in the diagnosis of venous impotence.
AB  - The gold standard in the diagnosis of venous impotence is cavernosometry. But a
      less invasive and time-consuming screening test for patients with a high
      probability of venous impotence is required. Therefore we evaluated 82 men with
      erectile dysfunction by color Doppler sonography after intracavernosal injection
      of 60 mg papaverine. 28 of them who had a poor erectile response but sufficient
      arterial inflow were included in this study. 6 patients who were previously found
      to have psychogenic impotence formed the control group. After pharmacological
      stimulation by papaverine, all patients were examined for 20 min by color Doppler
      sonography in order to detect diastolic flow velocities in the cavernosal
      arteries and erectile responses. Both groups of patients underwent pharmaco
      cavernosometry in a blind fashion afterwards. The diagnosis of venous impotence
      with color Doppler sonography was confirmed by dynamic pharmaco-cavernosometry in
      25 of 28 (89%) and 6 of 6 (100%) subjects of the study and control groups,
      respectively. Statistically, in the diagnosis of venous dysfunction, color
      Doppler sonography had a sensitivity of 100%, specificity of 66.6%, accuracy rate
      of 91% and a positive predictive value of 0.892. The gold standard in the
      diagnosis of venous impotence is still cavernosometry, but it seems that color
      Doppler sonography may provide a sensitive assessment of penile venous
      competence.

PMID- 8540159
TI  - Management of rectal injury during perineal prostatectomy.
AB  - 109 patients with locally confined prostate cancer underwent radical perineal
      prostatectomy. In 12 (11%) patients a rectal laceration was noted
      intraoperatively and closed in two layers. No patient had complications or
      prolonged hospital stay associated with the laceration.

PMID- 8540160
TI  - Transurethral laser urethrotomy with argon laser: experience with 900
      urethrotomies in 450 patients from 1978 to 1993.
AB  - From April 1978 to September 1993, the Department of Urology of Giessen Medical
      School used laser urethrotomy as standard endoscopic treatment in benign urethral
      strictures. In this period, 900 urethrotomies were performed in 450 patients. The
      majority of strictures treated were iatrogenic (65%), located in the posterior
      urethra (62.8%) and classified as short (< or = 1 cm) (71%). Argon laser
      urethrotomy was carried out in the 12 degrees position according to the technique
      of internal optical urethrotomy. An indwelling transurethral catheter was left
      for 48 h after urethrotomy. Uroflowmetry after argon laser urethrotomy revealed
      the efficacy of the method. A retrospective analysis of the operations was
      performed. Analysis showed that recurrence appeared on average after 15.2 months
      (range 1-39) in up to 70.1%. Nearly 50% of recurrence was evident within 1 year
      following surgery. Recurrence was independent of location, length and etiology of
      the stricture. We conclude according to our data that argon laser urethrotomy is
      technically feasible. Due to the high recurrence rate the method offers no
      advantage over conventional internal optical urethrotomy.

PMID- 8540161
TI  - Correlation of transrectal ultrasonographic findings of the prostate with the
      occurrence of detrusor instability in patients with benign prostatic hyperplasia.
AB  - Forty patients with benign prostatic hyperplasia were evaluated with urodynamics
      and transrectal ultrasonography. Seventeen patients were found to have detrusor
      instability while the remaining 23 did not. No significant differences were noted
      during ultrasonography in the estimated prostatic volume, the presumed circle
      area ratio and the incidence of finding prostatic calcification between these two
      groups. However, the incidence of detecting intravesical protrusion of the
      prostate is significantly higher in patients with instability than in patients
      with stable bladder (53 vs. 13%, p < 0.01). It is therefore postulated that
      intravesical protrusion may increase afferent impulses from the prostate and
      alter the stability status of the urinary bladder.

PMID- 8540162
TI  - Primary renal osteosarcoma. Case report and review of the literature.
AB  - We report a case of primary renal osteosarcoma diagnosed during the patient's
      life. A review of the literature revealed only 10 cases of primary osteogenic
      renal sarcoma. Differential diagnoses and possible treatment are discussed.

PMID- 8540163
TI  - Renal hemangiopericytoma. Case report and review of the literature.
AB  - Hemangiopericytoma (HPC) is an uncommon tumor which was first described in 1942.
      There are no unique radiological or clinical identifiers that can reliably aid in
      preoperative diagnosis. Surgery is the only reliable therapy as both chemotherapy
      and radiotherapy have proven ineffective in several series. The outcome is
      difficult to predict; the only reliable predictor is the presence or absence of
      metastasis. We report on a 63-year-old female with a large left renal HPC.

PMID- 8540164
TI  - Kidney conservation by delayed contralateral autotransplantation in a case of
      retroperitoneal lymphoma involving the ureter.
AB  - Large-cell retroperitoneal lymphoma was partially resected including a long
      segment of ureter. The proximal end of the ureter was clipped during surgery. A
      percutaneous nephrostomy was inserted after 48 h. Adjuvant chemotherapy was then
      delivered and the kidney was autotransplanted to the contralateral iliac fossa.
      Salvage of a hydronephrotic functioning kidney by nephrostomy and delayed
      contralateral autotransplantation in a case of huge retroperitoneal tumor
      involving the ureter has not, to the best of our knowledge, been described
      previously. This might suggest a reasonable approach for young patients with
      large retroperitoneal tumors involving long segments of the ureter.
      Autotransplantation was performed only after a disease-free status was confirmed
      following chemotherapy.

PMID- 8540165
TI  - Crossed ureteral ectopia with an ectopic blind-ending ureter.
AB  - A rare case of multiple urological anomalies is presented. The chief complaint of
      the patient, a 12-year-old girl, was urinary incontinence. Radiologic and
      endoscopic examinations revealed that the patient had a normal left kidney and
      ureter, a left ectopic blind-ending ureter that opened near the neck of the
      bladder, and right complete double ureters with an ectopic orifice that opened on
      the left of the external urethral meatus. This orifice was responsible for her
      urinary incontinence. Right ureteroneocystostomy was performed and the
      incontinence was cured. An attempt was made to explain the embryological origin
      of the anomalies observed in this case. We postulated that during development, on
      the left, there were three ureteral buds on the mesonephric duct. The first bud
      was at the normal position and drained the left kidney in a normal manner. The
      second bud was cranial from the normal position on the mesonephric duct and was
      associated with growth in an abnormal direction. This bud made contact with the
      upper portion of the right metanephric mass. The last bud grew between the two
      aforementioned buds. This bud was not draped by the metanephric mass and became
      the blind-ending ureter. On the right, one ureteral bud was located on the
      mesonephric duct and it made contact with a metanephric mass that became the
      right kidney. The upper part of the right kidney was drained by the ureter that
      had originally been located on the left mesonephric duct. This condition should
      be termed crossed ureteral ectopia rather than crossed renal ectopia, since the
      ureter was the structure that crossed.

PMID- 8540166
TI  - Inflammatory pseudotumor of the urinary bladder. A clinicopathological analysis
      of two cases.
AB  - We report 2 cases of inflammatory pseudotumor (IPS) of the urinary bladder
      observed in a man and a woman aged 63 and 66, respectively. Gross hematuria was
      the chief complaint. Immunohistochemical profile of IPS suggested a
      myofibroblastic proliferation. The DNA diploid pattern of IPS further supported
      the benign nature of the process. Immunohistochemistry seems to be the method of
      election in differentiating IPS from other spindle cell proliferations of the
      bladder.

PMID- 8540167
TI  - Primary non-Hodgkin's lymphoma of the male urethra. A case report and review of
      the literature.
AB  - Approximately 15-25% of malignant non-Hodgkin's lymphomas (NHLs) are primarily
      extranodal and only 2.7% of these are located in the genitourinary tract. Only a
      few particular cases of primary manifestation of NHL in the urethra have been
      described, most of them in female patients, whereas a secondary involvement
      occurs more frequently. In the present case a high-grade malignant NHL of the B
      cell type was located in the urethra of a 29-year-old male patient. No other
      manifestations of NHL could be found. After surgical removal of the urethral
      neoplasm the patient was treated with combined chemotherapy (6 cycles of the CHOP
      scheme). Thereafter, reconstruction of the urethra by the island flap method of
      Duckett was carried out. Two years after diagnosis the patient is alive and in
      complete remission with good functional and cosmetic results of surgery and a
      normal sexual life.

PMID- 8540168
TI  - Calculus in the vas deferens in a case of obstructive azoospermia.
AB  - Calcific lesions of the vas deferens are uncommon. We report a case of
      obstructive azoospermia in which a well-formed calcific lesion was found in the
      vas deferens during performance of a vaso-epididymotomy.

PMID- 8540169
TI  - [The surgical treatment of focal liver lesions].

PMID- 8540170
TI  - [The use of laser radiation in the combined treatment of suppurative
      complications from the osteosynthesis of the long tubular bones].

PMID- 8540171
TI  - [Anastomositis after gastric resection and its treatment].

PMID- 8540172
TI  - [A combination of multiple teratomatous multichambered cysts of the mesentery of
      the small and large intestines and of a teratoma of the left testis].

PMID- 8540173
TI  - [A new surgical approach to the membranous heart septum and a method for
      eliminating its defect by a closed procedure].
AB  - On the basis of an analysis of the operative wound parameters carried out in
      significant autopsy material it is concluded that longitudinal median sternotomy
      and anterolateral thoracotomy in the third intercostal right space permit
      reaching the upper edge of the membranous septum of the heart using the new para
      aortal access. This access allows to place a suture around the septum without
      opening the heart cavities by the closed method which is an alternative to the
      open correction of the interventricular septum defect in this ares. In clinical
      conditions the defect of interventricular septum was completely sutured in 3
      patients, partially--in 2 patients, was not sutured in 1. In one patient only on
      of two interventricular septum defects was closed.

PMID- 8540174
TI  - [The reinfusion of blood from the abdominal cavity in a penetrating knife wound
      of the stomach and jejunum].

PMID- 8540175
TI  - [Experience with single-stage operations using a modified A. G. Savinykh approach
      in the cardio- and gastroesophageal localization of cancer].

PMID- 8540176
TI  - [Arterial air embolism in explosive trauma to the lungs].

PMID- 8540177
TI  - [Endarterectomy of the carotid artery with the patient remaining conscious].
AB  - Based on an experience with carotid endarterectomies in 54 patients the authors
      show advantages of regional anaesthesia in conscious patients. It allow the well
      timed detection of symptoms of brain ischemia and prevention of them by means of
      temporal intraluminal shunts.

PMID- 8540179
TI  - [The treatment and prevention of postoperative pancreatitis].

PMID- 8540178
TI  - [The surgical treatment of chronic duodenal obstruction].
AB  - An analysis of indications to operative treatment has been made on the basis of
      clinical examinations of 162 patients with chronic disturbances of duodenal
      patency. The operation is indicated to patients with mechanical forms with any
      stage and to all the patients with the stage of subcompensation and
      decompensation. Operations were performed on 98 patients. In patients with the
      stage of subcompensation the operations were most effective which excluded the
      duodenal passage, especially antrumectomy after Roux with the elimination of the
      mechanical obstacles at the level of the duodenojejunal passage. At the stage of
      decompensation only such combined operations are thought to be effective which
      include additional drainage of the excluded duodenum.

PMID- 8540180
TI  - [A method of forming the gastric transplant for esophagoplasty].
AB  - A principally new method of forming the gastric transplant was developed on the
      basis of the anatomical investigation of the stomach blood supply, based on the
      intraorganic vascular way between 3 main collectors of the stomach--the right
      gastro-omental, left gastric and left gastro-omental arteries. The method was
      used in 65 patients operated upon with good results.

PMID- 8540181
TI  - [The individual immunotherapy of the intracranial complications after
      neurosurgical operations].
AB  - A system of individual immunotherapy is proposed which is based on the selection
      of an immunomodulator maximally suitable for the patients' immune system which is
      the therapeutic measure directed to the stimulation of forming the functional
      adaptive CNS dominant adequate to the pathological focus--the main component of
      sanogenesis in neuroanimatologic patients representing a complex of
      psychoneuroimmunoendocrine connections of the organism. As a result of
      immunotherapy the adequate adaptive CNS dominant makes concrete effector adaptive
      functional systems, determines the rate and sequence of the course of the
      adaptive reactions.

PMID- 8540182
TI  - [Selective surgical cholangiography].
AB  - Based on an analysis of data of ultrasonic examinations, cholangiography and
      operative findings, the authors consider that intraoperative cholangiography is
      necessary but in 48% of patients. The article gives grounds for indications to
      intraoperative cholangiography.

PMID- 8540183
TI  - [Laparoscopic appendectomy in acute appendicitis].
AB  - Laparoscopic technology was applied as diagnostic method in 608 patients, 50
      patients have undergone laparoscopic appendectomy. There were no diagnostic
      errors in laparoscopy application. Laparoscopic technology allowed to perform
      appendectomy quite safely and without any complications. This method permitted
      considerably reduce terms of treatment of the acute appendicitis patients and
      quickly restore their ability to work.

PMID- 8540184
TI  - [THe diagnostic and treatment characteristics of strangulated postoperative
      hernias].
AB  - Under analysis are clinical observations including 1028 patients with
      postoperative hernias. Emergency operations were performed in 62 of them for
      incarcerated hernias. Operations performed for postoperative hernias have
      peculiarities and if they are not taken into account recurrences and lethal
      outcomes can follow. Active methods of treatment of postoperative hernias in
      planned order are justified.

PMID- 8540185
TI  - [The importance of monitoring the motor activity of the small intestine in the
      postoperative period].
AB  - Monitor control of the digestive tract activity used in the postoperative period
      is of considerable significance in prophylactics of most dangerous complications.
      Monitoring at different levels of the digestive tract allows to at most decrease
      the danger of early enteral feeding, and to estimate the efficiency of numerous
      measures for the stimulation of intestinal activity.

PMID- 8540186
TI  - [The partial removal of nonorganic tumors of the retroperitoneal space].
AB  - An analysis of observation of 24 patients after partial resection of nonorganic
      retroperitoneal tumors has shown that 3 years survival of the patients subjected
      to partial resection of the tumor was equal to (57.7 +/- 10.8)% and 5 years
      survival was noted in (47.2 +/- 11.1)% of the patients. None of the patients
      subjected to explorative operations survived more than 3 years.

PMID- 8540187
TI  - [The intraorganic endolymphatic antibiotic therapy of lactation mastitis].

PMID- 8540188
TI  - [Postvagotomy diarrhea].
AB  - Main pathogenic factors of postvagotomy diarrhea are considered. Among them are:
      rapid emptying of the stomach due to the draining operation and accelerated
      passage of chyme along the small intestine, development of a relative
      insufficiency of digestion and absorption, entrance of the hyperosmolar content
      into the colon. Diarrhea appears more often after truncal vagotomy, is
      paroxysmal, then in time regresses and is successfully treated with
      benzohexamethonium and diet. Surgical correction as the inversion of the segment
      of the small intestine or restoration of the pyloric sphincter is required in
      single cases with critical continuously recurring form of diarrhea.

PMID- 8540189
TI  - [The treatment and prosthesis after an interilioabdominal amputation for sarcomas
      of the bones and soft tissues].
AB  - According to data of the Research Institute of Oncology named after N. N. Petrov,
      progress was achieved in treatment of patients who were subject to
      interilioabdominal amputation for malignant tumors. Five years survival after
      such operations was 19.7 +/- 3.4%. The prosthesis for patients subjected to
      interilioabdominal amputations was developed in Research Institute of Prosthesis
      (Saint Petersburg). It was successfully used in 11 patients in the age from 8 to
      51 years. The original construction of the prosthesis gives the patients
      possibility to walk without crutches, move along staircases with 25-cm-high
      footsteps and to use urban transport.

PMID- 8540190
TI  - [A first trial of the use of human recombinant interleukin (rIL-2) in patients
      with tumorous diseases].
AB  - Clinical approbation of human recombinant yeast human interleukin-2 (rIL-2) was
      carried out in 10 patients with III-IV stages of tumor that have undergone 65
      intravenous drop by drop infusions of the drug as a course of 5-11 injections in
      the dosage of 1-8 mln/un. The drug toxicity was shown in 4 mln and especially, in
      8 mln/un dose administration. That's why the dose of 1-2 mln/un is recommended.
      This dose was not followed by any serious complications, and the number of
      slightly complicated cases was significantly decreased as compared to similar rIL
      2 drug made by the "Cetus Corporation" firm. Immunostimulating effect of yeast
      rIL-2 was found which appeared to be able to reach it's maximum by 3-4
      administrations, with it's following disappearance or inversion, which may cause
      immunosuppression.

PMID- 8540191
TI  - [The optimization of the heparin prophylaxis of postoperative thromboembolic
      complications].
AB  - Using the methods of early diagnostics of phlebothromboses and thromboembolisms
      of pulmonary arteries allowed the author to establish that the optimum method of
      prophylactics of thromboembolic complications is considered to be the individual
      doses and schemes of administration of heparin which do not cause hypocoagulation
      shifts in the hemostasis system and greater bleeding of the wound at the early
      postoperative period.

PMID- 8540192
TI  - [Prehospital care in traumatic shock].
AB  - Clinical investigations performed in 735 patients have shown that in addition to
      the improvement of organisation of the medical aid and the universally recognized
      resuscitation measures for trauma shock, the prophylactics and treatment of
      intoxication, metabolic, immune and other disorders developing in the patients
      soon after trauma should be started as early as at the prehospital step.

PMID- 8540193
TI  - [The first surgical journal in Russia].

PMID- 8540194
TI  - [Combined thoracoscopy in thoracoabdominal wounds using ultrasound, the CO2 laser
      and the plasma jet].
AB  - Under analysis is an experience with treatment of 178 patients with
      thoracoabdominal wounds. The authors have developed a rational curative methods
      and original thoracoscopic techniques, which allowed to considerably reduce the
      amount of thoracotomies. Thoracoscopy was performed in 157 (88%) of 178 patients.
      Indications for thoracotomy were established in 7 patients, in 19 patients only
      drainage of the pleural cavity was made. Curative thoracoscopy was used in 131
      patients, in 60 of them ultrasonic glue hermetization of the lung wound was made,
      36 patients had laser photocoagulation of the lung wound, 21 patients had plasma
      coagulation of pleuro-pulmonary defects, in 14 patients--coagulated hemothorax
      was removed. Clinical effectiveness of thoracoscopic techniques was more than
      90%. Thoracotomy was performed in 28 (15%) patients, in 11 patients it was
      supplemented with diaphragmotomy. Laparotomy was performed in 167 patients.
      Lethality was 6.8%.

PMID- 8540195
TI  - [Reiter's disease as the source of errors in the diagnosis of traumatic
      arthritis].

PMID- 8540196
TI  - [Preoperative plasma- and thrombocytapheresis in patients with ischemic heart
      disease].

PMID- 8540197
TI  - [A combination of exchange plasmapheresis with the extracorporeal laser
      irradiation of the erythrocyte mass as a new component in the treatment of
      suppurative diseases in pulmonology].

PMID- 8540198
TI  - [A method of tubular resection of the stomach with the application of a lateral
      antireflux esophagofundic anastomosis in cardial ulcers].

PMID- 8540199
TI  - [A new method for the surgical treatment of umbilical hernias].

PMID- 8540200
TI  - [The surgical treatment of strictures and injuries of the extrahepatic bile
      ducts].

PMID- 8540201
TI  - [Plastic repair of the carotid artery in carotid endarterectomy].
AB  - The work is based on an analysis of results of 70 carotid endarterectomies
      performed on 68 patients aged from 43 to 67 years. 53% of the patients were
      operated upon at the stage of a relative compensation of brain blood circulation.
      Multiple character of injuries of the brachiocephalic arteries took place in
      70.5% of the cases. Plasty of the internal carotid artery is thought by the
      authors to be necessary by means of using a flap of lyophylized allopericardium,
      with the diameter of its orifice less than 8 mm.

PMID- 8540202
TI  - [The invagination of an excluded loop of small intestine after a jejunoileal
      bypass operation in patients with pathological obesity].

PMID- 8540203
TI  - [The achievements of cardiac electrotherapy].

PMID- 8540204
TI  - Quarantine, 'a ludicrous waste of money', select committee chairman says.

PMID- 8540205
TI  - Comparison of the workload of Dutch warmblood horses ridden normally and on a
      treadmill.
AB  - Six Dutch warmblood horses, ridden by an experienced rider, cantered 3320 m at a
      speed adapted to the individual horse's anaerobic threshold, under four different
      conditions: 1, on a firm shell track with the speed varying from 6.5 to 9.4 m/s;
      2, on a horizontal treadmill at the same speeds and for the same duration as in
      test 1; 3, on a horizontal treadmill for the same duration as in tests 1 and 2,
      but at a 10 per cent higher speed; and 4, on a treadmill at the same speed and
      for the same duration as in test 1, but at an inclination of 1 to 2 per cent
      adjusted individually to obtain heart rates similar to those recorded in test 1.
      On the basis of the heart rates and plasma lactate concentrations, the workload
      of the horses was significantly greater in the normal exercise test (1) than in
      the first treadmill test (2). Increasing the speed of the test on the horizontal
      treadmill by 10 per cent (test 3) resulted in heart rates and plasma lactate
      concentrations similar to those recorded in test 1. Inclining the treadmill on
      the basis of the heart rates achieved in test 1 had a less consistent effect than
      increasing the speed, but imitated a normal exercise test better than the
      horizontal treadmill test 2.

PMID- 8540206
TI  - An evaluation of the accuracy of ageing horses by their dentition: can a computer
      model be accurate?
AB  - The prediction of the age of a horse from its dentition has been widely accepted
      as an accurate technique, but recent reports have questioned this belief. In this
      study the dental features of 434 thoroughbreds of known age were documented and a
      multiple regression equation was calculated from the 13 dental features which had
      the highest correlation with true age. The accuracy of the ages assessed by a
      computer model were compared with the ages estimated by experienced equine
      clinicians. There was little difference between the accuracy of the computer
      model and the human observers, and neither method provided an acceptable level of
      accuracy for ageing horses from their dentition.

PMID- 8540207
TI  - Clinical, and light and electron microscopical findings in sows with cystitis.
AB  - The clinical findings, and urinary and morphological changes in the urinary
      bladder were investigated in 25 sows with a urinary tract infection. Eubacterium
      suis was isolated from 12 of the sows but not from the other 13. The clinical
      signs did not always correlate with the morphological changes. The only clinical
      sign indicating the beginning of cystitis appeared to be a significant
      bacteriuria. Other urinary changes occurred later when the inflammatory processes
      were more severe. In contrast with cystitis due to other bacteria, infection with
      E suis frequently resulted in a macrohaematuria and urinary pH values above 8.0.
      However, the light and electron microscopical findings in the bladder mucosa were
      similar in the sows with and without cystitis due to E suis. The transformation
      of goblet cells and the development of mucin cysts were probably due to the local
      bladder defence mechanisms. More severe lesions were observed with E suis
      infections, which resulted in changes in the ureterovesical junctions and in
      ascending renal infection and uraemia.

PMID- 8540208
TI  - Diagnosis of Brucella ovis infection of rams with an ELISA using protein G as
      conjugate.
AB  - The complement fixation and gel diffusion tests for Brucella ovis ram
      epididymitis were compared with an indirect ELISA using antigens from B ovis
      extracted in hot saline, rough B ovis lipopolysaccharide or a cytosolic fraction
      of rough B melitensis 115, and commercial anti-IgG (heavy and light chain
      specificity) or protein G conjugates. None of the antigens and conjugates used in
      the ELISA gave better results in terms of sensitivity and specificity than the
      complement fixation or the gel diffusion tests with the sera of 41 rams naturally
      infected with B ovis, 17 rams inoculated conjunctivally with B ovis and 53
      Brucella-free rams. The protein G conjugate significantly reduced the background
      reactivity of the sera from the Brucella-free rams but did not improve the
      sensitivity of the ELISA with the anti-IgG conjugate.

PMID- 8540209
TI  - Hydatid cyst development in an experimentally infected wild rabbit.

PMID- 8540210
TI  - Evaluation of homoeopathic treatment.

PMID- 8540211
TI  - Pregnancy diagnosis by ultrasound.

PMID- 8540212
TI  - Experimental poisoning of cattle by the mushroom Ramaria flavo-brunnescens
      (Clavariaceae): a study of the morphology and pathogenesis of lesions in hooves,
      tail, horns and tongue.
AB  - Seven 2 to 7-mo-old calves were fed the mushroom Ramaria flavo-brunnescens.
      Clinical signs of toxicosis included salivation, nasal serous discharge,
      smoothing of the dorsum of the tongue, increased sensitivity in the hooves,
      reddening of the coronary bands, loss of the long hairs of the tip of the tail,
      softening of the base of the horns, and progressive weight loss. Affected calves
      either died or were euthanatized in extremis within 12-37 d from the initiation
      of feeding. Postmortem examination confirmed changes observed in the live calves.
      Histopathologic changes were marked in those structures where hard keratinization
      occurred and there normally is a high uptake of sulfur in the form of cystine
      during the keratinization process. Toxicosis appeared to alter the metabolism of
      sulfur-containing amino acids in keratinocytes, particularly cystine, with
      resultant strength loss in the molecular structure of hard keratin and loosening
      of the hooves, hairs and horns, and flattening of the lingual filiform papillae.

PMID- 8540213
TI  - Chronic effects of hexachlorocyclohexane exposure: clinical, hematologic and
      electrocardiographic studies.
AB  - Twenty-six farm workers handling about 4 kg of commercial grade
      hexachlorocyclohexane (HCH)/y for 2-5 y and 21 control subjects were studied for
      chronic effects in clinical, hematological and cardiac variables. No clinically
      apparent morbidity was detected, but changes in hemoglobin and electrocardiograms
      were early effects of HCH exposure.

PMID- 8540214
TI  - Malathion and dichlorvos toxicokinetics after the oral administration of
      malathion and trichlorfon.
AB  - We studied the distribution and persistence of malathion and dichlorvos in the
      Wistar rat and established their toxicokinetics with the help of the PCNONLIN
      software program.

PMID- 8540215
TI  - Testicular toxicity of Di(2-ethylhexyl)phthalate in developing rats.
AB  - To understand the factors involved in the enhanced testicular toxicity of di(2
      ethylhexyl)phthalate (DEHP) in developing animals, po doses of 50, 100, 250 or
      500 mg DEHP/kg were administered to 25-d-old albino rats for 30 consecutive days.
      Activities of testicular and hepatic cytochrome P-450 enzymes were determined. A
      dose-dependent increase in the activities of lactate dehydrogenase and gamma
      glutamyl transpeptidase and a decrease in sorbitol dehydrogenase was observed in
      the testes. The activity of beta-glucuronidase increased at dosages of 250 and
      500 mg/kg, while acid phosphatase decreased. Testes had marked destructive
      changes in the advanced germ cell layers at dosages of 250 and 500 mg/kg, which
      supports biochemical studies indicating that DEHP interacts with the maturation
      process of the testes. The dose-dependent decrease in hepatic cytochrome P-450
      levels and the activities of ethylmorphine N-demethylase and aniline hydroxylase
      suggest that impaired metabolism of DEHP could lead to higher amounts of the
      diester or its metabolites reaching the testes; this may result in enhanced
      vulnerability of the testes to DEHP in developing animals.

PMID- 8540216
TI  - Furazolidone toxicosis in young broiler chicks: morphometric and pathological
      observations on heart and testes.
AB  - Broiler chicks 1 d and 3 w of age were given 0, 400, 800, or 1000 mg furazolidone
      (Fz)/kg feed for 4 w. Bi-ventricular heart dilatation (as measured by increases
      in ventricular diameter and thinning of the ventricular walls) was present in 1-d
      old chicks fed 800 mg Fz, whereas in 3-w-old groups these changes occurred at
      1000 mg Fz. There was no heart hypertrophy. Microscopic changes in the heart were
      not discernible in and Fz-fed birds. The liver had congestion and cytoplasmic
      vacuolation of hepatocytes. About 37-50% of the male birds in the different Fz
      fed groups had testicular degeneration varying from mild to cystic enlargement.
      The degenerated testes had dilatation of seminiferous tubules; in cystic testes
      the seminiferous tubules were extremely dilated and had flattened epithelium. The
      interstitial tissue between the dilated tubules was compressed and atrophic.

PMID- 8540217
TI  - Multiple birth concordance of street drug assays of meconium analysis.
AB  - To determine the prevalence of maternal drug usage in a mid-size midwestern city
      (population 250,000), we analyzed 1,175 consecutive meconium samples from the
      neonatal intensive care unit from March 1991 through December 1993. We focused on
      meconium assays from multiple births as a quality control method. Meconium
      specimens were analyzed using fluorescence polarization immunoassay (FPIA-Abbott
      Diagnostics) with confirmation done by gas chromatography/mass spectrometry
      (GC/MS). Cutoff concentrations of 5 ng/g were utilized for all analytes. A total
      of 151 samples (12.9%) tested positive. Cocaine-exposed neonates had the highest
      positive rate (63 or 5.4%), followed by marijuana (52 cases or 4.4%),
      cocaethylene (12 cases or 1%), and amphetamine (1 case or 0.1%). Nine patients
      (0.8%) had multiple drugs present. There were a total of 23 sets of multiple
      births (21 twins, 2 triplets); 20 sets of multiple births (42 patients) had
      concordance with all births testing negative. Three sets of twins had concordance
      in testing positive, with 1 twin testing positive for cocaine while the other
      twin tested positive for cocaine and marijuana. No absolute discordance of twins
      assays were noted. The rate of maternal drug use through measurement of meconium
      is about 12.95% in this mid-sized midwestern city. Twin studies provide an
      excellent method for verifying fetal drug exposure. The use of sets of multiple
      births provides a unique internal quality control mechanism in determining fetal
      drug exposure.

PMID- 8540218
TI  - Chromium fetotoxicity in mice during late pregnancy.
AB  - Female mice received 250, 500 or 750 ppm chromium (VI) as potassium dichromate in
      drinking water on days 14 to 19 of pregnancy. Gestational weight gain of mothers,
      fetal weight and crown-rump length decreased in the 500 and 750 ppm groups. The
      high-dose group also had significantly higher incidences of postimplantation
      loss. Significant increases in drooping wrists, subdermal hemorrhagic patches,
      kinky and short tails, and reduced ossification were also found in the 750 ppm
      group. Chromium levels were increased in a dose-dependent manner in maternal
      blood and placenta and in fetuses. Our study suggests a risk to the developing
      fetus if the mother is exposed to high concentrations of chromium (VI) during
      pregnancy.

PMID- 8540219
TI  - Bittering agents: their potential application in reducing ingestions of engine
      coolants and windshield wash.
AB  - Ethylene glycol automobile engine coolants and methanol-based windshield washer
      liquids are toxic. Despite international attempts to improve the safety of these
      products through better labelling and packaging, accidental and intentional
      ingestions continue a source of poisonings worldwide. The rejection of bitter
      tasting substances forms part of the human defense against ingestion of harmful
      substances. Denatonium benzoate (DB) is currently recognised as a means to
      prevent ingestion of ethyl alcohol intended for industrial use. This study
      investigated the use of this bitter substance also as a deterrent against
      ingesting ethylene glycol and methanol. The palatability of ethylene glycol and
      methanol with and without the addition of DB was assessed using a human taste
      panel; 30 ppm DB rendered each product intolerable to the panel. The addition of
      DB to ethylene glycol engine coolants and methanol-based windshield washer
      liquids at low concentrations could afford protection against accidental
      ingestions.

PMID- 8540220
TI  - Trace element concentrations in tissues of goats from Alabama.
AB  - Liver, kidney and muscle tissues of goats slaughtered in Alabama were analyzed
      for Cu, Fe, Mn and Zn. The Cu, Fe and Mn concentrations were significantly higher
      in livers than in kidneys and muscles. The Zn was significantly higher in livers
      and muscles than in kidneys. The concentrations of Cu, Fe, Mn and Zn in muscle
      were not significantly different between male and female goats. However, the Cu,
      Fe and Mn in livers and Fe in kidneys were significantly different between males
      and females. The concentrations of Fe, Mn and Zn in livers, Fe and Zn in muscles,
      and Fe in kidneys were significantly different between young and old goats. The
      Cu, Mn and Zn in kidneys were not significantly different between the young and
      old.

PMID- 8540221
TI  - Effects of acute 2,4-dichlorophenoxyacetic acid on cattle serum components and
      enzyme activities.
AB  - The acute toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in
      cattle. Steers were dosed po with 100, 300 or 600 mg 2,4-D/kg bw. Serum aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (AP), O-glutamyl transferase (O-GT), creatine kinase (CK), lactate dehydrogenase
      (LDH) activities and urea, creatinine, glucose, total proteins and albumin levels
      were determined at intervals after dosing. The lowest 2,4-D dose did not change
      the biochemical parameters studied; the 300 mg/kg dose decreased AST, O-GT and CK
      activities and increased urea and glucose levels; the highest dose of 2,4-D
      increased LDH and CK activities and protein, urea, creatinine and glucose levels.
      These changes were time and dose-dependent and completely reversible. Acute 2,4-D
      intoxication disrupted the serum levels of several enzymes and blood components
      which mainly reflect kidney and muscle damage induced by the herbicide.

PMID- 8540222
TI  - In vitro comparison of aldicarb oxidation in various food-producing animal
      species.
AB  - Aldicarb (ALD) metabolism was studied in vitro using hepatic microsomes from
      chickens, rabbits, sheep and pigs. The microsomal activities of mono-ooxygenase
      enzymes (flavin-containing and cytochrome P-450-dependent mixed function
      oxygenases) were compared by measuring the quantity of the 2 oxidized
      metabolites, ALD sulfoxide and ALD sulfone, produced during 60 min of incubation.
      Pig microsomes produced the greatest quantity of ALD sulfoxide and the lowest
      quantity of ALD sulfone; the latter being produced in greater quantities in sheep
      than in chickens and rabbits. Aldicarb and its metabolites were degraded fastest
      in rabbits, probably by hydrolytic reactions. These in vitro results, which are
      consistent both with the levels of cytochrome P450 found in hepatic microsomes
      and previous in vivo data on ALD kinetics in pigs, rabbits and chickens, indicate
      that preliminary in vitro studies can limit the necessary use of animals for drug
      metabolism experiments.

PMID- 8540223
TI  - Tissue and serum swainsonine concentrations in sheep ingesting Astragalus
      lentiginosus (locoweed).
AB  - Locoweed intoxication or locoism results when animals continuously graze certain
      plants of the general Astragalus or Oxytropis. The locoweed toxin, swainsonine,
      is water soluble and is rapidly absorbed and eliminated. The purpose of this
      study was to determine the distribution of swainsonine in tissues of sheep eating
      locoweed and to determine if the tissue swainsonine concentrations change with
      continued locoweed ingestion. Fifteen cross-breed whethers were divided into 3
      groups of 5 each and fed alfalfa pellets (Group 1) or alfalfa pellets with 10%
      Astragalus lentiginosus for 13 d (Group 2) or for 21 d (Group 3). After the
      feeding periods, the animals were slaughtered and tissues were collected, frozen
      and later analyzed for swainsonine using an in vitro, alpha-mannosidase
      inhibition assay. Significant alpha-mannosidase inhibitory activity (interpreted
      as ng/ml of swainsonine) was detected in whole blood, skeletal muscle, brain,
      kidney, liver, thyroid and urine. The swainsonine concentrations in tissues were
      significantly correlated with daily swainsonine intake (r = 0.58 to 0.96). With
      the exception of kidney, longer exposure did not result in significant increases
      in the swainsonine concentrations in blood, muscle, brain, liver or thyroid.
      Liver had the highest swainsonine concentrations with 3049 +/- 1952 and 3947 +/-
      457 ng/ml (mean +/- SD) in Groups 2 and 3 respectively. Swainsonine
      concentrations varied widely within the groups suggesting individual animal
      variability in swainsonine absorption, metabolism and excretion. These findings
      suggest that swainsonine is present in tissues of animals eating locoweed and
      that in most tissues the amount was directly correlated to the swainsonine dose
      ingested, but not to the length of exposure.

PMID- 8540224
TI  - Effect of sulfamethazine on mixed function oxidase in chickens.
AB  - Sulfamethazine (SMZ) ip administration for 3 d to chickens showed significant
      induction of cytochrome P-450 levels and in the activities of aminopyrine N
      demethylase, aniline hydroxylase and glutathione s-transferase at the dosage of
      150 mg SMZ/kg body weight. Cytochrome P-450 and the activity of aniline
      hydroxylase were significantly decreased at 300 mg SMZ/kg body weight when
      compared to 150 mg SMZ/kg body weight. Other doses produced no significant
      changes in the parameters studied. One hundred fifty mg SMZ/kg for 1 or 3 d
      caused significant induction of cytochrome b5, cytochrome P-450, the drug
      metabolizing enzymes and glutathione s-transferase; however, 5 d of SMZ produced
      no significant changes. The in vitro 10 mM SMZ inhibition of aminopyrine N
      demethylase and aniline hydroxylase and the induction of enzymes at 150 mg SMZ/kg
      body weight indicates that SMZ is a substrate of the mixed function oxidase
      system and may be an inducer of specific forms of cytochrome P-450.

PMID- 8540225
TI  - Pyridoxine as therapy in theophylline-induced seizures.
AB  - Theophylline-induced seizures have significant morbidity and mortality and are
      difficult to treat. Theophylline therapy for asthma has been observed to depress
      plasma pyridoxal 5'-phosphate (PLP) levels which may decrease gamma-aminobutyric
      acid (GABA) synthesis and thereby contribute to seizures. We hypothesized that
      treatment with pyridoxine might prove beneficial in theophylline-induced
      seizures. One hundred thirty-nine mice were injected with 250 mg theophylline/kg
      ip and 89 mice were injected with 250-750 mg pyridoxine/kg ip as treatment.
      Decreased rates of seizure (42 vs 70%, p < 0.002) and death (29 vs 56%, p <
      0.002) were observed. Six New Zealand White rabbits were given 115 mg
      theophylline/kg iv over 50 min followed by treatment with an iv bolus of 115 mg
      pyridoxine/kg, with subsequent continuous drip infusion of 230 mg/kg over 50 min.
      Serum theophylline levels and plasma PLP levels showed significant negative
      correlation prior to pyridoxine infusion with a mean peak theophylline level of
      182 micrograms/ml and a mean low PLP level of 64 nM/L. Electroencephalogram (EEG)
      tracings were obtained before infusions, during theophylline infusion and during
      pyridoxine infusion. All 6 rabbits developed abnormal EEGs during theophylline
      infusion and all 6 rabbit EEG patterns returned to baseline during treatment with
      pyridoxine. These findings suggest that pyridoxine may partially reverse
      theophylline-induced central nervous system toxicity.

PMID- 8540226
TI  - Four-week oral toxicity study of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in uremic
      rats.
AB  - A short-term oral toxicity study of 1,2-dimethyl-3-hydroxypyrid-4-one (L1), a
      promising oral chelating agent for the treatment of iron and aluminum overload,
      was carried out in uremic rats. L1 was administered to male uremic rats by
      gastric intubation at 0, 20, 40, 80 or 160 mg/kg/d for 4 w. Body weight and food
      and fluid intake were monitored daily. Complete hematologic examinations, serum
      biochemical parameter determinations and histological examinations were carried
      out. Although body weight gain was significantly reduced at 80 and 160 mg/kg/d,
      there were no effects of L1 on food and fluid consumption. There were no
      significant differences between controls and L1-treated groups in most of the
      hematological and biochemical parameters analyzed. No significant dose-dependent
      changes in relative organ weights were noted. The non-observed-adverse-effect
      level (NOAEL) for L1 in uremic rats was 40 mg/kg/d. According to the results of
      this study, uremia did not increase the toxic effects of L1.

PMID- 8540227
TI  - Accumulation of trace elements in sheep and the effects upon qualitative and
      quantitative ovarian changes.
AB  - The distribution of Cu, Zn, Fe, Mo, Se, As, Cd and Pb was determined in the
      organs of sheep that died of Cu intoxication from a Cu plants emissions.
      Simultaneously, quantitative and qualitative changes in the ovaries were
      evaluated. In sheep that died of copper intoxication, the highest Cu levels were
      in the liver (1797 +/- 946.1 mg/kg dry matter) and the kidneys (425.5 +/- 426.4
      mg/kg dry matter). The liver and kidneys accumulated Zn, whereas Fe was primarily
      accumulated by spleen and kidneys. Selenium was mainly in the ovaries and uterus
      (7.72 +/- 4.88 and 5.30 +/- 5.33 mg/kg dry matter respectively). The ovaries and
      the uterus were the organs that accumulated As, Cd and Pb, respectively.
      Histological changes in the number of ovarian follicles and the increased
      occurrence of primary atretic follicles indicated alterations in the membrane
      structures and organelles of oocytes and in the follicular cells of the stratum
      granulosum.

PMID- 8540228
TI  - An estimation of Citrullus colocynthis toxicity for chicks.
AB  - Citrullus colocynthis seed was fed at 2% and 10% of the basal diet to 7-d-old
      Bovans-type chicks for 6 w. Average body weights and efficiency of feed
      utilization were markedly depressed in the chicks on 10% Citrullus feed, and the
      serum activities of LDH, AST and CK and concentrations of total lipid and zinc
      were significantly increased. The concentration of serum total iron binding
      capacity was particularly reduced in chicks on 2% Citrullus feed. The
      concentrations of other serum and blood constituents and of hepatic copper,
      manganese and zinc were not significantly changes. Lesions seen in the
      intestines, livers, kidneys and other tissues were fully reversed 4 w after
      removal from the experimental diet.

PMID- 8540230
TI  - Washington's experience and recommendations Re: Anticoagulant rodenticides.

PMID- 8540229
TI  - Zearalenone mycotoxicosis in piglets suckling sows fed contaminated grain.
AB  - An outbreak of zearalenone mycotoxicosis occurred between early March and mid
      April involving 62 suckling piglets of both sexes. The clinical picture was
      characterized by edematous swelling and reddening of the vulva, sometimes
      associated with reddening and/or necrosis of the tail. Six female piglets had
      congenital lesions of the external genitalia while in the remainder clinical
      signs appeared 2 to 3 d after birth. No sows ingesting the contaminated feed had
      signs of hyperestrogenism. The distribution of affected litters showed a
      correlation with poor hygienical conditions. Zearalenone residues were detected
      only in feed samples from mangers where the hyperestrogenic syndrome occurred.

PMID- 8540231
TI  - Valerian overdose: a case report.
AB  - We present the first reported case of valerian (Valeriana officianalis) overdose.
      This herb is popular as a sedative but little is known about its toxic effects.
      The patient presented with mild symptoms, all of which resolved within 24 h.
      Valerian overdose, at approximately 20 times the recommended therapeutic dose,
      appears to be benign.

PMID- 8540232
TI  - Overdose of colchicine in a three-year-old child.
AB  - We report the case of a previously healthy girl who developed a multi-systemic
      failure after an inappropriate dose of colchicine. The patient recovered
      completely and had no residual effects.

PMID- 8540233
TI  - Epidemiology of ingestions in a regional poison control center over twenty years.
AB  - This analysis was conducted to demonstrate the pattern and changes of potential
      intoxications reported to a German regional poison control center from 1974 to
      1993. During this period 155,654 calls were reported of which 111,313 were
      analyzed. The remaining 44,341 were either of minor importance of preventive
      calls; 56% referred to children and 44% to adults. Substance categories most
      commonly implicated were drugs, with a yearly average of 37.6% of the total,
      followed by household articles (31.2%), plants (9.7%) and chemicals (5.9%). In
      pediatric cases household articles were the most frequent source of ingestion
      followed by drugs, plants and nutritional substances, whereas in adults drugs
      were followed by household articles, chemicals and pesticides. Only 13.4% of all
      ingestions were classified as toxic or very toxic. There were no major changes in
      the incidences of the different substance categories during the 20 years.
      However, there were some changes in the pharmaceuticals, probably due to the
      introduction of new drugs or the withdrawal of the OTC-status of selected drugs.

PMID- 8540234
TI  - Utilization of expert consultants by poison centers in the United States.
AB  - A survey was mailed to 103 poison centers in the US during March 1990 to
      characterize the use of outside experts for patient-specific problems; 69 centers
      responded. Outside experts were utilized by 64 centers (93%) with contact being
      made < 3 times monthly by 58% of the respondents. There were 84 different types
      of experts utilized with near equal distribution of medical and non-medical
      specialties. A minority (18%) of the centers had organized a committee of experts
      and only 7% of the centers compensate outside experts. There was no association
      between the utilization of experts and characteristics of a poison center, such
      as receipt of state funding, funding level or certification. With the variety of
      practices in utilizing experts, poison centers may wish to review their
      approaches to the use of outside consultants.

PMID- 8540235
TI  - Evaluation of the US pharmacopeia adsorption tests for activated charcoals and
      proposals for changes.
AB  - The current USP adsorption tests for activated charcoals, involving methylene
      blue (MB) and strychnine sulfate (SS), were conducted for 6 activated charcoals
      having surface areas ranging from 600 to 2000 m2/g. The MB test is relatively
      complex and tedious, and uses a pass/fail criterion which is of such small
      magnitude that substantial uncertainties are likely. The SS test is only
      qualitative. Modification, using quantification of the turbidities, permitted
      quantitative interpretation. The test was failed by 2 charcoals of surface area
      660 m2/g or less, and was passed by 4 charcoals of 720 m2/g surface area or
      higher. Neither test was able to reflect the substantial drug adsorption
      differences which exist for charcoals of average, above average, and high surface
      areas. Alternative tests for MB and SS were developed and evaluated using 6
      charcoals. These tests, which are proposed for consideration by the US
      Pharmacopeial Convention, are simpler and faster than the current tests and yield
      precise values for the percentages of the 2 compounds adsorbed. Moreover, they
      clearly reflect the wide differences in adsorption performance of charcoals
      having widely different surface areas. Minimum percent adsorption values that
      must be attained for a charcoal to qualify as "USP grade" are proposed for both
      alternative tests (these would not exclude any current USP grade charcoal).
      Performance classifications of charcoals into categories of Low, Average, Above
      Average, and High are also proposed for both tests. These are shown to correspond
      to surface area ranges of < 700, 700-950, 950-1200, and > 1200 m2/g,
      respectively.

PMID- 8540236
TI  - Earth day, clean water and...

PMID- 8540238
TI  - Genotyping of isolates of Taylorella equigenitalis from thoroughbred brood mares
      in Japan.
AB  - Profiles of the genomic DNA of 104 strains of T. equigenitalis isolated from
      brood mares with contagious equine metritis in Hokkaido during the breeding
      seasons from 1980 to 1993, as well as those of five strains (SS28, EQ56, EQ59,
      EQ70 and HH139) previously isolated in Japan were examined after restriction
      digestion and crossed-field gel electrophoresis. These profiles were essentially
      identical to each other and the various isolates and strains appeared to have a
      common genotype, designated 'genotype J', with respect to two restriction
      enzymes, ApaI and NotI. These results suggest a common source for all these
      isolates obtained over the course of more than 10 years in Japan.

PMID- 8540237
TI  - A detection assay for Campylobacter fetus in bovine semen by restriction analysis
      of PCR amplified DNA.
AB  - A rapid screening assay for Campylobacter fetus in bull semen was developed using
      the polymerase chain reaction (PCR) and restriction endonuclease analysis (REA)
      to complement isolation by culture. An oligonucleotide primer pair (C1/C2) from
      the hypervariable region of 16S rRNA of C. fetus was used to amplify a 362 base
      pair fragment by PCR. The PCR/REA assay, which is completed in 10 hours, detected
      as few as three C. fetus subsp. venerealis cells in experimentally infected raw
      bull semen and in semen diluted with milk or egg yolk Tris (EYT). All the strains
      tested, of both subspecies of C. fetus, were amplified, as were some other
      Campylobacter species. Restricting the amplified products by AluI differentiated
      C. fetus from the other organisms. There was no visible product generated by PCR
      from C. sputorum subsp. bubulus, a saprophytic organism found in the prepuce of
      bulls, or from seven other species of bacteria found in semen. A modification of
      the PCR assay, using another primer pair (C3/C2) and two temperature PCR cycling
      conditions, increased the probability of detecting C. fetus subsp. venerealis.
      PCR amplification followed by REA could be used to screen bovine semen rapidly
      for C. fetus. In most cases, sequencing of C1/C2 PCR generated products would be
      preferable for distinguishing between the two subspecies of C. fetus.

PMID- 8540239
TI  - A preliminary study on the effect of dietary supplementation with cod liver oil
      on the polyunsaturated fatty acid composition of boar semen.
AB  - Eight mature Norwegian Landrace boars, of proven fertility and in routine semen
      production for AI, were fed individually with the same basic diet for 9 weeks.
      One group of 4 animals served as the control, the remaining 4 boars received a
      daily supplement of 75 ml cod liver oil (CLO-group). Fifteen consecutive semen
      samples were collected from each boar. The fatty acid composition of the semen
      was determined, and the content of the 15 most numerous fatty acids with a chain
      length longer than 12 carbon atoms was followed over time. In both groups, the
      proportion of 16:1n-7 decreased significantly, while 16:0 and 22:6n-3 (DHA)
      increased. By the end of the experiment, DHA had tended to increase and 22:5n-6
      to decrease to a greater extent in the CLO-group. A significant difference
      between the groups was seen for one n-6 PUFA (22:4n-6), which remained unchanged
      in the control group but decreased in the CLO-group. No change was seen in
      docosapentaenoic acid (22:5n-3) and eicosapentaenoic acid (20:5n-3) was not found
      in any sample. These results indicate that CLO supplementation affects the fatty
      acid composition of boar semen. There were no significant differences in the non
      return rates (4-25 days) between the two groups before, during or after the
      experiment.

PMID- 8540240
TI  - Detection of beta 2-agonists in milk replacer.
AB  - beta 2-Agonist drugs may be illegally used as growth promoters for feedlot
      calves, when mixed into milk replacer immediately before feeding. To check for
      the presence of clenbuterol, salbutamol and terbutaline in such food, an
      analytical system was established using a screening method based on two
      commercial qualitative competitive ELISA tests, with antibodies raised against
      the arylamino group and the t-butyl group. The extraction procedure was based on
      precipitation of the milk samples with acetonitrile followed by filtration. The
      absence of any significant interference by other substances in the filtrate
      allowed detection of beta 2-agonist drugs in spiked samples at the lowest
      concentration having a repartitioning effect (50 ppb for clenbuterol, mabuterol
      and terbutaline, 500 ppb for salbutamol). In view of a false positive response
      with tetracycline in milk samples and a cross-reaction between clenbuterol and
      mabuterol, an HPLC-MS technique was developed which, after extraction and
      purification of the samples with SPE C18 Polar Plus, was able to confirm the
      presence of these drugs. The good recovery after extraction (ranging from 84% to
      90.2%) and the low detection limit with this method (250 ng/ml for clenbuterol,
      mabuterol and terbutaline, and 2.5 micrograms/ml for salbutamol) allowed easy
      confirmation and simultaneous detection of the four beta 2-agonists at the lowest
      concentrations at which they are used in adulterated milk for calves.

PMID- 8540241
TI  - Comparative ultrastructural studies on Besnoitia besnoiti and Besnoitia caprae.
AB  - Comparative transmission electron microscopy on Besnoitia besnoiti and on a
      strain of Besnoitia derived from goats in Kenya revealed that the two organisms
      differ in their pellicle, micropore, microtubules, nucleus, wall-forming body 1
      (W1), amount of lipids and amylopectin. Thus the caprine besnoitia is probably a
      different organism and the term Besnoitia caprae should continue to be used.

PMID- 8540242
TI  - The effect of diethylene glycol monoethyl ether as a vehicle for topical delivery
      of ivermectin.
AB  - The effect of diethylene glycol monoethyl ether (DGME; Transcutol) on the
      permeation of ivermectin, a broad-spectrum antiparasitic agent, through bovine
      skin was evaluated by in vitro permeation experiments followed by serial
      sectioning of the skin to assess the amount of ivermectin retained in the skin.
      Ivermectin permeation through bovine skin was enhanced by DGME and this
      enhancement was DGME-concentration-dependent. Permeation of ivermectin was
      effectively enhanced in vehicles with low proportions of DGME, but the magnitude
      of permeation enhancement decreased as the proportion of DGME increased. The
      permeation was accompanied by the formation of cutaneous depots of ivermectin.
      Furthermore, the data indicated that the flux and the cutaneous accumulation of
      ivermectin were sensitive to the concentration gradient of DGME across the skin.
      This suggested that ivermectin was permeating with DGME, in which it is very
      soluble. Hence, the enhancing mechanism involves solubilization of the ivermectin
      by DGME and the transport of DGME itself across the skin. Based on these results,
      DGME appears to be a potential vehicle for topical delivery of ivermectin by
      transport through the skin and through formation of cutaneous depots of
      ivermectin.

PMID- 8540243
TI  - Dose-response relationship for the antipyretic effect of meloxicam in an
      endotoxin model in cats.
AB  - The antipyretic efficacy of meloxicam was evaluated in a feline endotoxin model
      using a replicated change-over design. Twelve adult cats of both sexes were
      allocated at random to three experimental groups. At 30 min prior to the
      intravenous (i.v.) endotoxin challenge (0.5 microgram/kg body weight(b.w.)), 2
      animals in each group received an i.v. injection of 0.1, 0.3 or 0.5 mg
      meloxicam/kg b.w. and the two remaining animals in each group received
      physiological saline. In a second phase, 21 days later, the meloxicam/placebo
      treatment was exchanged within each group. The rectal temperature and scores for
      general demeanour were determined at 30-min intervals from before dosing to 300
      min after the endotoxin challenge. Haematological parameters were analysed before
      and 60 min after administration of endotoxin. The results indicated a significant
      dose-dependent antipyretic response to meloxicam after endotoxin challenge. The
      antipyretic response in the medium- and high-dose meloxicam groups did not differ
      significantly, but both were significantly different from the low-dosage group.
      The individual effects of endotoxin on general demeanour were rather variable but
      meloxicam tended to have a beneficial effect. Endotoxin induced a reduction in
      the white blood cell count but this was not influenced by meloxicam. It was
      concluded that the pyretic endotoxin model is very suitable for studying new
      NSAIDs in cats and that the optimum single dose of meloxicam in this model was
      0.3 mg/kg b.w.

PMID- 8540244
TI  - Characterization of normal tidal breathing flow-volume loops for thoroughbred
      horses.
AB  - The purpose of this study was to characterize the normal equine tidal breathing
      flow-volume loop (TBFVL). The study was performed using 18 healthy Thoroughbred
      horses. TBFVLs constructed from data collected from resting horses had a typical
      biphasic inspiratory and expiratory phase. The interindividual variability of the
      indices used to describe TBFVLs was in the range 16-32%, which is comparable to
      the variability of other measures of equine pulmonary mechanics. The large
      variability of these data probably limits the value of resting TBFVL indices for
      detecting subclinical respiratory conditions in individual horses. Factor
      analysis of these data revealed that in excess of 90% of the variance of the
      initial response variables could be explained in terms of three common factors.
      Varimax rotation of these three common factors provided three subsequent factors
      that were readily identifiable as (1) a factor describing the time-volume
      relationships of TBFVLs, responsible for 81% of the total variance, (2) a factor
      explaining the expiratory portion of the TBFVL, explaining 12% of the variance,
      and (3) a factor describing the inspiratory portion of the loops, responsible for
      the remaining 7% of the variance. The analysis also provided standardized factor
      scoring coefficients for use in subsequent studies using similar experimental
      techniques.

PMID- 8540245
TI  - Vector control for malaria and other mosquito-borne diseases. Report of a WHO
      study group.
AB  - Since the Ministerial Conference on Malaria in 1992, which acknowledged the
      urgent need for worldwide commitment to malaria control, efforts have been
      directed to implementation of a Global Malaria Control Strategy. Vector control,
      an essential component of malaria control, has become less effective in recent
      years, partly as a result of poor use of alternative control tools, inappropriate
      use of insecticides, lack of an epidemiological basis for interventions,
      inadequate resources and infrastructure, and weak management. Changing
      environmental conditions, the behavioural characteristics of certain vectors, and
      resistance to insecticides have added to the difficulties. This report of a WHO
      Study Group provides guidelines for the planning, implementation and evaluation
      of cost-effective and sustainable vector control in the context of the Global
      Malaria Control Strategy. It reviews the available methods - indoor residual
      spraying, personal protection, larval control and environmental management -
      stressing the need for selective and flexible use of interventions according to
      local conditions. Requirements for data collection and the appropriate use of
      entomological parameters and techniques are discussed and priorities identified
      for the development of local capacity for vector control and for operational
      research. Emphasis is placed both on the monitoring and evaluation of vector
      control to ensure cost-effectiveness and on the development of strong managerial
      structures, which can support community participation and intersectoral
      collaboration and accommodate the control of other vector-borne diseases. The
      report concludes with recommendations aimed at promoting the targeted and
      efficient use of vector control in preventing and controlling malaria, thereby
      reducing the threat to health and socioeconomic development in many tropical
      countries.

PMID- 8540246
TI  - [Motivation and reinforcement in the systemic mechanisms of behavior: the dynamic
      engrams of reinforcement].
AB  - Theoretical and experimental data are presented which give evidence that in
      systemic organization of behaviour motivation and reinforcement interact in
      separate brain neurons. It has been shown that the immunity mechanisms
      participate in motivation-reinforcement interaction. It is postulated that in the
      process of learning the reinforcement by means of feedback afferentation forms
      molecular engrams on the neuronal structures of action acceptor. Such engrams are
      built by DNA and protein synthesis in ribosomes. Later on these engrams can be
      activated by the dominant motivation.

PMID- 8540247
TI  - [Cortical activation: the role of the indeterminacy/determinacy of a situation].
AB  - Ontogenetic data concerning EEG correlates of activation during attention were
      analysed in various paradigms. The results were compared with the degree of
      certainty/uncertainty of situation established by the instruction or determined
      by the subject. A proposition is made about two activation types in human EEG
      desynchronization and synchronization within the alpha-band. Both activation
      types which facilitate brain organization of present or forthcoming activity
      realize it in their own ways. Desynchronization which leads to disintegration of
      the system promotes formation of the new one. Synchronization immediately
      facilitates functional integration of brain structures involved into a specific
      form of activity. The results of processing and evaluation of information which
      characterize certainty/uncertainty of situation determine the balance between the
      two activation types.

PMID- 8540248
TI  - [The dependence of the heart rhythm on anxiousness as a stable individual
      characteristic].
AB  - In 90 subjects (25 males and 65 females) aged 17-19 heart and respiration rates
      were telemetrically recorded with a "Sport" polygraph under conditions of rest
      and arithmetical load (periods of 3 min each). Spectral analysis of heart rate
      and respiration and statistical processing was performed off-line by an IBM PC XT
      with the software package PFE2. Anxiety was tested according to Spielberger State
      Trait-Anxiety Inventory with Hanin modification and strength of excitation and
      inhibition according to Strelau Temperament Inventory. It was shown that the
      group characterized by the high trait-anxiety had significantly higher resting
      heart rate and Baevskii index of strain than the group with low trait-anxiety.
      The groups differed also in R-R interval variability (standard deviation) under
      arithmetic load. In the group with high trait-anxiety R-R interval variability
      was lower than in the other group mainly in two frequency bands of R-R power
      spectrum, i. e., those of respiratory arrhythmia (RA) and Traube-Hering-Mayer
      waves (THM). Mental load evoked an increase in the heart rate and Baevskii index
      and decrease in the power of RA and THM frequency bands. Such peculiarities of
      the heart rate in both groups during the periods of rest and informational load
      can be explained in the framework of reciprocal relationship between orienting
      (lower trait-anxiety, lower heart rate, higher R-R interval variability mainly in
      RA and THM bands of R-R power spectrum) and defensive reflexes (higher trait
      anxiety, higher heart rate, lower R-R interval variability, in particular in RA
      and THM bands of R-R power spectrum.

PMID- 8540249
TI  - [The bioelectrical correlates of the personality anxiousness of 2 strong types of
      higher nervous activity].
AB  - Bioelectrical correlates of personality anxiety were studied in subjects with
      strong types of higher nervous activity. It was shown that the index of general
      power of the alpha-rhythm inversely depended on the level of anxiety. In sanguine
      persons the low level of anxiety and incapacity for vivid reproduction of fear
      were associated with frequent change of asymmetry sign in all EEG recordings.
      Choleric persons were characterized by the high level of anxiety and the stable
      dominance of one of the hemispheres manifested in EEG of the frontal and temporal
      areas.

PMID- 8540250
TI  - [The electroencephalographic correlates of the intellectual abilities of
      adolescents].
AB  - Analysis of correlation between intellectual faculties of schoolchildren and
      spatiotemporal organization of their brain electrical activity was carried out.
      The less intelligent teen-agers showed more expressed alpha-activity in the EEG
      of rest, higher level of EEG coherence, and insignificant restructuring of the
      rhythmical activity under conditions of "open eyes" as compared with the "closed
      eyes". In the resting EEG of highly intelligent teen-agers beta-frequencies were
      more expressed and desynchronization after opening the eyes was clearly
      detectable.

PMID- 8540251
TI  - [The conditioning of the N100-P200 component of the human visual evoked potential
      by using biofeedback].
AB  - Subjects were instructed to modify their N100-P200 component of VEP (in Cz
      recording) within selected time window. The aim was to increase the number of
      VEPs for which the amplitude of segment in question exceeded the definite
      threshold. The success in task performance suggests several modifications of the
      to-be-conditioned segment through different mechanisms. Of our 26 subjects, 14
      were able to modify their VEPs according to the task demands. However, the latter
      subjects could be divided into 2 groups on the basis of the rate of increase in
      the number of correct responses under conditioning. Subjects which did not
      succeed in task performance could be also classed into 2 groups: one group with
      statistically negligible changes and the other decreasing the number of correct
      responses. ANOVA has shown significant distinctions in task performance for the
      groups with different levels of self-estimation of tiredness after experiment and
      different personal strategies. The success in task performance is likely to be
      dependent on the values of Eysenck questionnaire scales and topography of alpha
      activity.

PMID- 8540252
TI  - [Delayed reactions of active avoidance in white rats under conditions of an
      alternative choice].
AB  - It was shown that if the rats had been learned and then tested using conventional
      pain punishment of erroneous choice they were able to solve the problem of
      alternative choice only in the period of immediate action of conditioned stimuli.
      If the pain punishment for erroneously chosen compartment had not been applied in
      animal learning and testing, rats successfully solved the problem of alternative
      choice even after 5-second delay. Introduction of pain punishment led to the
      frustration of earlier elaborated delayed avoidance reactions. Analysis of the
      obtained results allows us to argue that the apparent incapability of white rats
      for solving the problems of delayed avoidance is caused by simultaneous action of
      two different mechanisms, i.e., those of the active and passive avoidance rather
      than short-term memory deficit.

PMID- 8540253
TI  - [The ontogenetic characteristics of the motor exploratory reaction of female
      laboratory mice during exposure to the urinary pheromones of sexually mature
      males].
AB  - Motor exploratory activity of 36 and 41 days old female laboratory mice CBA and
      C57BL/6 and their hybrids CBAB6F1 was studied after the action of urine of male
      mice CBA and C57BL/6. Five parameters were recorded. It was shown that formation
      of behavioural response to the socially important stimulus of pheromonal nature
      occurred during puberty process depending on the donor and recipient genotypes
      and on the previous experience of interaction with the stimulus. The critical
      period of formation of this reaction was revealed in the ontogeny of females.

PMID- 8540254
TI  - [The solving of the Revecz-Krushinskii test by Norway rats].
AB  - Reasoning abilities of Norway rats were studied in Revecz-Krushinskii test. In
      this test 12 opaque plastic cylinders were placed in a row. Rats obtained the
      bait (sunflower seeds) after tipping the goal cylinder (from the feeder situated
      under it) independently of the number of one tipped before. Positions of the
      baits were changed in the following order: the cylinder No 1 in the first trial,
      No 2--in the second and so on up to the twelfth one. Rats were tested 3 times (12
      trials, once a week) in a rectangular box with a starting chamber and a working
      part with a special device which excluded the influence of olfactory stimuli.
      Solution scores demonstrated that rats chose cylinders in the nonrandom manner
      and their behaviour scores were similar to those of crows and monkeys. Analysis
      of errors and strategies of behaviour of rats showed that quick improvement of
      feeding was at least partly determined by easy acquisition of recent food
      positions (i.e., the algorithm of shifting).

PMID- 8540255
TI  - [The capacity for transitive inference in birds: the solving of the Gillan test
      by Corvidae and pigeons].
AB  - Transitive inference in birds was investigated using D. J. Gillan (1981)
      experimental procedure. In the initial experiment 11 pigeons and 14 crows were
      trained to differentiate colour stimuli in pairs of adjacent ones from five
      stimulus succession A, B, C, D, and E. The birds learned that stimulus E was
      associated with more food items than D, D, in turn, signalled less food items
      than C, and so on. Then the birds were tested by newly formed pairs of stimuli
      from the same succession (BD, CE, and BE). There were two series of testing. Both
      crows and pigeons solved the transitive inference test successfully (choosing D
      and E) in the series with small numbers of food items. In the series with larger
      numbers of food items the pigeons shifted to random performance while in crows
      the percentage of correct choices decreased. The proportion of adequate test
      solutions grew with the absolute difference between the numbers of food items
      associated with stimuli to compare. The capacity for solving the test in our
      experiments can be considered as the result of immediate comparison of the
      absolute numbers of food items associated with each stimulus. Thus, the data
      cannot be regarded as the final proof that these species are capable for
      transitive inference.

PMID- 8540256
TI  - [The physiological characteristics of new agressotropic neuropeptides].
AB  - Physiological effects of the structural analogs of earlier unknown neuropeptides
      isolated from the bovine brain were studied. It was shown that intraventricularly
      and intraperitoneally administered peptides strongly affected different kinds of
      aggressive behaviour of rats. In addition, the peptides under study influenced
      various kinds of behaviour presumably linked to formation of the aggressive state
      of the animal (food and water intake, fear, locomotion). The findings suggest
      that the peptides modulate dopamine-, serotonin- and glutamatergic
      neurotransmission which underlie neurochemical mechanisms of aggressive activity.

PMID- 8540257
TI  - [Generalized and signal-specific long-term nociceptive sensitization in the snail
      Helix lucorum].
AB  - Neurophysiological and behavioural correlates of the long-term sensitization were
      investigated in Helix lucorum small. Application of 10% quinine solution on the
      snail's head initiated a long-term (for more than 24 hours) facilitation of
      defensive reactions. The behavioural effects correlated with the changes in
      evoked and spontaneous activity of L-PP11 neurons, i.e., facilitation of synaptic
      components in responses to testing stimulation, increase in membrane excitability
      and depolarization. Efficacy of sensitization depended on the duration of the
      experimental procedure. After daily training site-specific and modality-specific
      effects dominated (i.e., more expressed facilitation of responses to testing
      stimulation of the sensitized body site than that of the other sites or to
      testing stimulation of the same modality as sensitizing stimulation). After 3
      days of training the effects of general sensitization were predominantly
      observed, i.e., facilitation of neuronal responses to stimulation of different
      modalities and body sites, depolarization of the membrane and increase in its
      excitability.

PMID- 8540258
TI  - [The formation of taste aversion and preference under conditions of protein
      synthesis inhibition in rats].
AB  - The study is devoted to the role of protein synthesis in formation of
      chemosensory memory in rats. Two experimental models of taste memorizing were
      used, i.e., conditioned taste aversion (CTA) caused by association of succharin
      intake with being poisoned by lithium chloride, and increased taste preference
      (ITP) caused by the influence of primary consumption of succharin solution on its
      repeated intake. It was found out that CTA was not formed under conditions both
      of 43% inhibition of brain protein synthesis by cycloheximide and of 59% its
      inhibition by 8-azaguanine. Cycloheximide but not 8-azaguanine prevented
      formation of ITP. A proposal was made about participation of different spectra of
      protein and peptide molecules in formation of taste aversion and preference. The
      effect of protein synthesis inhibitors on the process of taste memory retrieval
      was not found.

PMID- 8540259
TI  - [The characteristics of the neurophysiological mechanisms of the acquisition and
      extinction of defensive behavior in rabbits under the action of the
      immunomodulator neurotropin].
AB  - Effects of neurotropin (NSP), a substance extracted from the inflammatory dermis
      of rabbits inoculated with Vaccine virus, on avoidance conditioning and
      extinction were studied in rabbits. Intravenous administration of NSP produced
      reorganization of the neuronal activity in CA1 area of the hippocampus making it
      more regular. Under the influence of NSP conditioned heart rate bradycardia
      became more expressed. NSP led to longer persistence of avoidance response during
      extinction. Under the action of NSP time patterns of intersignal neuronal
      activity, heart rate and respiration were similar to those during conditioning
      trials. The results suggest that NSP administration activates intersignal
      retention process which results in more steady consolidation of avoidance
      behaviour.

PMID- 8540260
TI  - [The neuronal reaction of the sensorimotor cortex to stimulation of the lateral
      hypothalamus with a background of the microiontophoretic administration of
      tetragastrin and bradykinin: the role of food reinforcement].
AB  - Reactions of neurons of sensorimotor cortex to stimulation of the "center of
      hunger" in the lateral hypothalamus were studied at the background of
      microiontophoretic application of gastrin, and bradikinin in satiated freely
      behaving rabbits under conditions of presence or absence of free access to food.
      It was shown that food reinforcement essentially changed reactions of neurons to
      electrical stimulation of the lateral hypothalamus at the background of
      application of neuropeptides under study. This probably led to specific
      reorganization in the neuronal system which underlay the mechanism of interaction
      between motivation and reinforcement influences on the neurons.

PMID- 8540261
TI  - [A comparative analysis of the complex realization of the goal-directed behavior
      of animals under chronic morphine and cocaine administration].
AB  - A new approach to estimation and prediction of morphine and cocaine effects was
      proposed based on the analysis of animal behaviour directed to a satisfaction of
      one of the main biological needs, thirst. Both morphine and cocaine did not
      essentially effect the level of the basic biological (drinking) motivation by the
      index of the general volume of liquid consumption. Both drugs produced opposite
      effects on the duration of recognition/manipulation and drinking components of
      the structure of water-reinforced instrumental act. The proposed methodology is
      of diagnostic and prognostic value in respect of the complex behavioural effects
      of the drugs and presumably some other active factors.

PMID- 8540262
TI  - [The open-field test as a prognostic criterion of resistance to emotional stress
      in Wistar rats].
AB  - The open-field test was studied as a predictive behavioural criterion of
      resistance to emotional stress. Emotional stress was induced in Wistar rats by
      immobilization with simultaneous electrical skin stimulation 3 days after
      behavioural testing. Severity of stress was evaluated by the rate of survival and
      changes in the weight of thymus and adrenals. Rats which displayed longer
      latencies of the first movement in the open field and of crossing the central
      areas, lower locomotor and exploratory activity, higher rate of defecation had
      lower survival rate and more pronounced adrenal hypertrophy in stress.

PMID- 8540263
TI  - [The electrical activity of the isolated rabbit cerebral cortex after
      acetylcholine application].
AB  - Within 6 weeks after surgical isolation of a wide area of the rabbit neocortex
      EEG spectra were studied before and after acetylcholine application to the
      isolated cortex. Acetylcholine application initiated an intricate multiphase
      reaction in the sensorimotor and visual areas of the isolated cortex which lasted
      for more than 10 minutes. It consisted of an increase in EEG amplitude and
      progressive change in EEG rhythms, i. e., enhancement of the theta-waves and
      appearance of higher frequencies (up to 15 Hz) in the EEG. In the control series
      of experiments (rabbits with the intact neocortex) acetylcholine application
      produced an increase in EEG amplitude and enhancement of peaks in EEG spectrum.
      The response of the isolated cortex is interpreted as an artificially induced
      activation. The distinctions between responses of the isolated and intact
      neocortex are explained by retention of subcortical control over the state of the
      intact cortex.

PMID- 8540264
TI  - [Changes in the indices of neuronal functional activity under the action of
      piracetam as a possible basis for realizing the effects of nootropic agents].
AB  - Effects of piracetam (PA, 4-20 mM) on some electric characteristics of neuron
      activity were studied in vitro in identified neurons of Lymnaea stagnalis.
      Stimulation, single-electrode voltage clamping and recording of activity of the
      neuron were realized via the same intracellular microelectrode. PA-induced
      alterations of the characteristics under study were observed in 60-70% of
      recorded neurons. Modifications of action potential generation threshold, of the
      slope and shape of steady-state membrane current-voltage characteristics and
      appearance of PA-induced transmembrane ion currents occurred more frequently than
      changes in other parameters. Typically, Ca channel blockers (nifedipine and Cd
      ions) reversed or reduced the influence of PA on the studied characteristics of
      tested cell activity, i. e., acted as PA antagonists. This suggests that
      realization of observed PA effects is due to its action on Ca channel
      functioning. Selective modification of the latter can determine development of
      various PA effects at the cellular level. An assumption is discussed that
      piracetam, being a highly efficient cellular adaptogen and modifying specifically
      Ca channels of cells, is capable of moving them to a new level of functioning
      which is necessary for ensuring complex forms of nervous activity.

PMID- 8540265
TI  - [The reinforcing properties of psychostimulating preparations on models of
      conditioned-reflex place preference in mice].
AB  - Secondary reinforcing properties of cocaine, amphetamine, methylcathinone,
      ephedrine, apomorphine, and bromocriptine were studied with the aid of
      conditioned place preference technique in mice. All explored drugs, except
      apomorphine, induced dose-related conditioned place preference in mice. Technique
      of comparative analysis of addictive potentialities of drugs is proposed.
      Procedure and analysis aspects of described technique as well as the
      possibilities of its implementation for screening of addictive substances are
      discussed.

PMID- 8540266
TI  - [The microcirculation and the succinate and NADH dehydrogenase activities of the
      brain in neurotic disorders of the higher nervous activity in white rats].
AB  - A correlation was made between microcirculation and energy metabolism in the
      brain of 50 neurotized rats. Neurotic disorders were defined by characteristics
      of conditioning, arterial pressure, breathing rate and heart rate. In vivo
      biomicroscopy revealed modification of the state of blood vessels at rest and
      inverted reaction of brain pial vessels of neurotized rats to bilateral occlusion
      of common carotid arteries. Ratio of activities of respiratory cycle enzymes
      (succinate and NADH-dehydrogenases) was indicative of hypoxic state of the
      animals under study.

PMID- 8540267
TI  - [The neurotropic effects developing on the administration of Freund's complete
      adjuvant (FCA) to rats].

PMID- 8540268
TI  - [An analysis of evoked brain activity by computing the average duration of the
      wave half-period].
AB  - Poststimulus spectral EEG changes and their relation to averaged evoked potential
      (AEP) were analysed using average wave half period length (AWHL) computation
      method. In 5 healthy subjects increase of AWHL in the latency range of slow AEP
      components was revealed during simple motor reaction to visual stimuli. It was
      shown that AWHL increase could not be explained by AEP contribution to single
      realizations and/or by the process of suppression of EEG rhythms.

PMID- 8540269
TI  - European certification of clinical competence in adult echocardiography issued in
      Belgium. The Steering Committee of the Belgian Working Group on Echocardiography
      and Cardiac Doppler.
AB  - In accordance with the European proposals, adapted guidelines are proposed for a
      certification of clinical competence in adult echocardiography, with
      transoesophageal echocardiography as a special option. The conditions required to
      be candidate to the certification, the exemptions of practical training for long
      term echocardiographers and the organisation of the training itself are
      successively considered. Standards for training, site accreditation, official
      logbook characteristics, minimal numbers of examinations and minimal stage
      duration are defined. Content of theoretical training, as well as organisation of
      formal and informal education and of final examination, are described.

PMID- 8540270
TI  - Left systolic atrioventricular plane displacement in the assessment of myocardial
      viability in patients with previous myocardial infarction.
AB  - In order to detect myocardial viability in coronary artery disease patients (CAD)
      with a previous myocardial infarction and dysfunction of the left ventricle (LV),
      the reliability of the left atrioventricular plane displacement (LAVPD) during
      low dose dobutamine stress echocardiography (DSE), was validated. The study
      population consisted of 70 CAD patients and 35 age and sex matched healthy
      subjects. From the apical four and two chamber views the LAVPD was recorded and
      measured by M-mode echocardiography, at four sites corresponding to the septal,
      lateral, anterior and inferior walls of the LV, prior and during the DSE (5-10
      micrograms/kg/min). All patients underwent exercise SPECT Thallium-201 with four
      hour redistribution and rest-reinjection, in order to determine tissue viability.
      Intraobserver and interobserver variability for the LAVPD was insignificant (5.8%
      and 7.2%, respectively). Healthy subjects exhibited a significant and equally
      distributed maximal increase of the LAVPD, at all sites during dobutamine
      infusion (DI) (p < 0.001). Patients also, showed a significant maximal increase
      of the LAVPD during DI, at all asynergic sites in which viable tissue was found
      (p < 0.001). However, in the asynergic sites without viable tissue the LAVPD did
      not significantly change (p < 0.05). Selecting a LAVPD increase of > 2 mm to
      detect viable myocardium at any asynergic site of LV, resulted in a sensitivity
      of 91% and specificity of 89%. When DSE was used for the detection of viable
      myocardium, sensitivity and specificity were found to be 80% and 87%
      respectively. The proportion of agreement between the two above mentioned methods
      was 82%. When the two methods were in agreement, the positive and negative
      predictive values were 94% and 97%, respectively. The validity of the above
      mentioned increase of the LAVPD was also prospectively examined in a similar
      group of 35 CAD patients exhibiting myocardial dysfunction as a result of a
      previous myocardial infarction (sensitivity 85% and specificity 90%,
      respectively). CONCLUSIONS: 1) The assessment of left LAVPD during DI is a new
      quantitative, accurate method with a low intraobserver and interobserver
      variability, in detecting viable myocardium. 2) Combination of this method and
      DSE proved good diagnostic markers of myocardial viability.

PMID- 8540271
TI  - The sinus node and the autonomic nervous system in normals and in sick sinus
      patients.
AB  - To determine the evolution with age, of extrinsic and intrinsic sinus node
      electrophysiological parameters and to assess the role of each component of the
      autonomic nervous system relative to age in patients with and without sick sinus
      syndrome, electrophysiological studies of sinus node function were performed in
      227 patients subdivided into four groups according to the results of their
      electrophysiological testings: group I included patients with normal extrinsic
      and intrinsic sinus node function, group II patients with exclusive extrinsic
      sinus dysfunction, group III patients with exclusive intrinsic sinus dysfunction
      and group IV patients with extrinsic and intrinsic sinus node dysfunction. The
      electrophysiological study was performed 4 times: at basal state, after
      sympathetic, autonomic and parasympathetic blockades. Whatever the sinus node
      function (normal or abnormal) the extrinsic sinus node electrophysiological
      variables did not correlate with age; inversely all the electrophysiological
      measurements of the intrinsic sinus node (normal or abnormal) lengthened
      progressively with age, suggesting an ageing phenomenon of the intrinsic sinus
      node throughout life. Moreover, the study of the percentage of chronotropy of the
      sinus node electrophysiological variables shows a predominance of vagal tone in
      young subjects, whereas sympathetic activity is most prominent in elderly
      patients with and without sick sinus syndrome. Besides, sympathetic activity
      increases and vagal tone decreases with increasing age in normals whereas the age
      related modifications of each component of the autonomic nervous system in sick
      sinus patients vary according to the type of sinus node dysfunction. The sinus
      node (normal or pathological) represents an equilibrated system: the age-related
      modification of the autonomic nervous system counterbalances the senescence of
      the intrinsic sinus node in such a way that the basal electrophysiological
      characteristics remain stable throughout life.

PMID- 8540273
TI  - Successful radiofrequency ablation of a true paraHissian accessory pathway.
AB  - Radiofrequency catheter ablation seems to become a first-line therapy for
      patients with paroxysmal tachycardias using an accessory pathway. We report the
      case of a 31-year-old woman who suffered from drug-resistant recurrent
      reciprocating tachycardia, using an uncommon accessory pathway. The 12-lead
      electrocardiogram in sinus rhythm showed the following characteristics: a
      positive delta waves in leads I, II, aVL, aVF, QRS axis = 0 degrees, R/S in lead
      V1 < 1, and a special QRS pattern in the precordial leads (QS or Qr in V1-V3 and
      QRS transition > V3). A deep septal parahissian accessory pathway has been
      localized using classic endocardial mapping procedures and has been confirmed
      during successful radiofrequency catheter ablation. Normal auriculo-ventricular
      conduction has been totally preserved. No complications or recurrence were
      observed during the follow-up. We have reviewed the electrophysiologic criteria
      to confirm this rare accessory pathway location.

PMID- 8540272
TI  - The predictive value of troponin T in patients who underwent an extracardiac
      surgery operation.
AB  - Purpose of the study is the research of the diagnostic value of the determination
      of Troponin T in relation with the other cardiac enzymes in patients who
      underwent extracardiac surgery operation. METHODS: 42 pts (M = 24, F = 18, mean
      age 51.7 +/- 17 years) who underwent a surgery operation were studies. For all
      pts serum enzyme CPK, CPK MB, SGOT and Troponin T was determined 24 hours before
      and after the operation. RESULTS: increased value of CPK was observed in all
      patients. In 14.3% of pts was found abnormal value of CPK. In 1 pt CPK MB was
      found increased. In no one of the above pts was observed an increased value of Tr
      T. No one of the pts had ECG changes and clinical symptoms indicative of ischemic
      heart disease. CONCLUSIONS: these results suggest that the determination of Tr-T
      in serum is more useful diagnostic index for myocardial cell injury in pts who
      underwent an extracardiac surgery because is not detected in skeletal muscle
      injury.

PMID- 8540274
TI  - A cardiac giant hydatid cyst of the interventricular septum masquerading as
      ischemic heart disease: role of MR imaging.
AB  - Cardiac echinococcosis is a very rare disease, especially in girls. We report a
      case of interventricular septum echinococcosis. A 14-year-old girl was referred
      for chest pain. Magnetic resonance imaging and two-dimensional echocardiography
      revealed a cyst in the distal interventricular septum. We concluded that MR
      imaging is useful in diagnosis and planning of surgery. Cardiac hydatid cyst
      should be considered in the differential diagnosis of patients with anginalike
      pain in endemic areas.

PMID- 8540275
TI  - [Descending pathways of the basal ganglia].

PMID- 8540276
TI  - [Progress in molecular histochemistry].

PMID- 8540277
TI  - [Tissue localization and possible function of type VI collagen].
AB  - Type VI collagen was once considered a minor collagen, but now it is known as a
      major component of the extracellular matrices of most tissues. Type VI collagen
      tetramers aggregate into beaded filaments with repeats of approximately 100 nm,
      and the beaded filaments align laterally to form type VI collagen periodic
      fibrils by incubation with acidic ATP solution. Polyanionic ATP could cause
      lateral alignment of type VI collagen beaded filaments. Since the periodic
      structure is observable by transmission electron microscopy, we can examine the
      tissue distribution of type VI collagen by ATP treatment. Moreover, the
      interaction of type VI collagen with other extracellular matrix components can be
      examined by combining ruthenium red (RR) staining, which specifically interacts
      with tissue glycosaminoglycans (GAGs), with the ATP treatment. I here describe
      the localization and possible function of type VI collagen examined in our
      laboratory. After ATP incubation, numerous type VI collagen periodic fibrils
      appeared closely associated with striated collagen fibrils (mouse cornea and
      fibrous layer of mandibular condyle), with trophoblastic and endothelial basal
      lamina (human placenta), or with cell surface of fibroblasts (mouse tendon) and
      synovial cells (mouse synovium). The dark bands of the type VI collagen periodic
      fibrils were stained by RR, indicating the association of proteoglycans
      (PGs)/GAGs with this collagen. If the mouse corneal tissue was digested with
      chondroitinase ABC or testicular hyaluronidase prior to ATP treatment, type VI
      collagens were segregated to form periodic structures apart from striated
      collagen fibrils. In the mouse mandibular condyle, hyaluronidase digestion before
      ATP treatment caused unmasking of type VI collagen.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8540278
TI  - A comparative study of the correlation of weights of the body, testis, and
      epididymis in the goat, ram, bat and rat.
AB  - This study was undertaken to correlate the weights of the body (Bw), testis (Tw),
      epididymis (Ew), cauda epididymidis (CEw), length (TL), diameter (TD), and area
      (TLD) of testis in adult Wistar rats, Eidolon helvum (mogachiropteran bat), red
      Sokoto goats, and white Yankassa rams. The results showed that it was only in the
      Wistar rats that TL, TD and TLD correlated significantly with TW (p < 0.01). Bw
      showed no significant correlation with Tw in the mammals. Tw correlated very
      significantly (p < 0.01) with Ew, and CEw in the rat, goat, and ram but not in
      the bat. These findings suggest that testicular weight, a measure of daily sperm
      production, relates with testis length, diameter and area, measures of testicular
      size, only in Wistar rat but not in the red Sokoto goat, white Yankassa ram, or
      Eidolon helvum; and that body weight has no relevance in the assessment of the
      reproductive performance of the males of these mammalian species. It further
      suggests that in the bat, a flying mammal, testicular weight does not relate to
      indices of sperm transport (epididymal weight) and storage (cauda epididymal
      weight) unlike in the terrestrial mammals studied.

PMID- 8540279
TI  - [Study on the distribution of muscle spindles in the rat extensor digitorum
      longus muscle].
AB  - The distribution of muscle spindles (MS) in the extensor digitorum longus (EDL)
      muscle of the rat hind limb was morphologically studied on a series of
      longitudinal cryostat sections. The intrafusal muscle fibers were brownishly
      stained with the acetylcholinesterase reaction, and the mucopolysaccharide
      contained in the equatorial periaxial space was stained with alcian blue. This
      double-staining method made it easy for us to find the MS and to decide the
      equatorial portion and the whole extension of MS. From a series of camera lucida
      drawings the distribution of all MS was reconstructed on a sheet of paper and
      three-dimensionally imaged on a personal computer using image reconstructing
      software. The MS were distributed mainly in the superficial and lateral part of
      EDL muscle. Additionally, an ATPase reaction was employed to detect the red
      muscle fibers, and it was confirmed that their distribution of them is similar to
      that of MS.

PMID- 8540280
TI  - On the developing periodontal ligament of rats, using a new specimen preparation
      method for SEM in comparison with histochemistry.
AB  - To visualize the cells and fibers of the developing periodontal ligament (PDL) by
      scanning electron microscope (SEM), we examined a new tissue preparation method
      including decalcification, sectioning by cryomicrotome, and chemical treatment
      for removal of cells or collagen fibers. The advantages of this method were as
      follows: (1) it was possible to expose the restricted area, (2) it caused no
      damage by heat or various embedding agents such as paraffin or resin, and (3) it
      was possible to make comparisons the SEM observation with histochemical or
      immunohistochemical observation using the neighboring sections. We could classify
      the development of PDL into three stages by alkaline phosphatase (ALPase)
      activity and observe each stage by this method. Stage I was the zone of dental
      follicle proper that showed negative ALPase activity. Stage II was the tissue
      surrounding the disrupted Hertwig's epithelial root sheath (HERS) which evinced
      intense ALPase activity, and stage III was the further advanced zone of
      differentiation that displayed moderate ALPase activity. Using this new method
      for SEM, cells with many processes and thin fibers were seen irregularly at stage
      II. On the other hand, at stage III, fibers were seen as interconnecting
      meshworks of thick bundles and cells that showed regularly arranged rows running
      obliquely to the surface of the root and alveolar bone. At the transition between
      stages II and III, the thickness and orientation of fibers changed abruptly.

PMID- 8540281
TI  - [Function of myoepithelial cells in salivary secretion: reevaluation of the
      expulsion theory].
AB  - Although myoepithelial cells have been suggested to provide the expulsive force
      to secrete saliva into the mouth, direct evidence to support this idea has been
      lacking. We examined the structure and distribution of myoepithelial cells in rat
      parotid and sublingual glands, and observed whether contraction occurs in living
      acini during secretion in vitro. Scanning electron microscopy and the whole mount
      alkaline phosphatase histochemistry revealed well-developed myoepithelial cells
      around the sublingual acini. In the parotid gland, myoepithelial cells were
      abundant along the intercalated ducts but were sparse around the acini. A stress
      fiber-like distribution of actin fibers was demonstrated by rhodamine phalloidin
      staining in the myoepithelial cells of sublingual glands. Under a video-enhanced
      microscope, a rapid shrinkage of sublingual acini was observed within 2 min of
      secretory stimulation. However, the shrinkage was slight and transient, and
      thereafter the acinar shape was almost maintained over 30 min, during which time
      considerable amounts of secretory granules were released. It was suggested that
      the major function of myoepithelial cells in salivary secretion is the support
      for the glandular structure through isometric contraction. This conclusion is
      compatible with our previous morphometric analyses on fixed cells (Noriko Shoi:
      Kitasato Med 24: 432-434, 1994).

PMID- 8540282
TI  - [On the hepatic artery arising from the superior mesenteric artery].
AB  - This report describes anomalous cases having the so-called gastro-lienal and the
      hepato-mesenteric trunks instead of the celiac and superior mesenteric arteries.
      These anomalous cases were divided into 4 types and 6 classes according to
      difference of running form of the hepatic artery as follows. Type I: This hepatic
      artery arose from an unusual hepato-mesenteric trunk off the aorta immediately
      inferior to the gastro-lienal trunk. This artery ascended behind the portal vein
      and splenic vein, passed around in front of the left side of the portal vein, and
      arrived in the liver. Type II: This hepatic artery arose from an unusual hepato
      mesenteric trunk off the aorta immediately inferior to the gastro-lienal trunk.
      This hepatic artery ascended behind the portal vein, passed around front from the
      right side of the portal vein, and arrived in the liver. Type III: This hepatic
      artery arose from an unusual hepato-mesenteric trunk off the aorta immediately
      inferior to the gastrolienal trunk. This hepatic artery of III-P ascended between
      the portal vein and pancreas, III-A ascended in front of the pancreas. Type IV:
      This hepatic artery arose from an unusual hepato-mesenteric trunk off the aorta
      immediately inferior to the gastro-lienal trunk. This type of hepatic artery
      ascended behind the superior mesenteric vein, passed around in front from the
      right side of the portal vein, and arrived in the liver. This hepatic artery of
      IV-P ascended behind pancreas, IV-A ascended in front of the pancreas.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8540283
TI  - [A case of congenital quadricuspid pulmonary valve].
AB  - The present report describes a case of congenital quadricuspid pulmonary valve,
      encountered during the dissection of an 84 year-old Japanese female cadaver at
      Kanazawa Medical University. In this case, no evidence of heart failure was found
      clinically or pathologically. The semilunar valve on the right posterior was the
      biggest and that of the left anterior was the smallest.

PMID- 8540284
TI  - [A case of the three branches of the celiac trunk arising directly from the
      abdominal aorta].
AB  - The present report describes the dissection of an 81 year-old Japanese female
      cadaver in the Kanazawa Medical University in which the celiac trunk was not
      present, that is, the left gastric, the splenic and the common hepatic arteries
      arose independently from the abdominal aorta in that order. In this case, the
      left gastric artery arose from the front wall of the abdominal aorta at a level
      between the 11th intercostal posterior and subcostal arteries. The splenic artery
      arose from the left front wall of the abdominal aorta about 5.0 mm below the
      origin of the left gastric artery. The common hepatic artery arose from the right
      front wall of the abdominal aorta about 4.0 mm below the origin of the splenic
      artery. The superior mesenteric artery dividing from the front wall of the
      abdominal aorta about 9.0 mm below the origin of the common hepatic artery, ran
      about 17.0 mm to give off the right accessory hepatic artery upwards to the
      right. This case belongs to type V of Morita's classification (1935), but was not
      described in Adachi's classification (1928). There seems to be only six such
      cases reported so far in Japan.

PMID- 8540285
TI  - [Computerized three-dimensional reconstruction of human embryos and their organs
      using the "NIH image" software].
AB  - Three-dimensional structures of human embryos and their internal organs were
      reconstructed on a CRT from their serial histological sections using a free
      computer software system "NIH Image." It was possible to rotate the computer
      images on CRT and to make cut models on any desired plane. In addition, various
      developmental changes could be animated by artificial "morphing" between the
      models at different stages. Computer graphic modeling should be of great value in
      the study of normal and abnormal morphogenesis. The "NIH Image" software is
      freely available via computer networks and has a lot of advantages over
      previously developed software programs used for three-dimensional reconstruction.

PMID- 8540286
TI  - Stimulated thyrotropin and prolactin secretion in lactating and non-lactating
      women.
AB  - During the postpartum period, lactation is initiated by a massive release of
      prolactin which, in turn, reflects reduced dopaminergic inhibition of the
      pituitary lactotrophs. This postpartum prolactin rise can be prevented by
      administration of dopamine agonists. The release of thyrotropin (TSH) is also
      controlled by dopaminergic inputs and, therefore, TSH secretion may also be
      affected by postpartum alterations in dopaminergic activity. To gain further
      insight into the regulation of TSH and prolactin secretion during the postpartum
      period, we compared the basal and stimulated TSH and prolactin levels of
      postpartum lactating (n = 10) and non-lactating women (treated with 5 mg
      bromocriptine daily, n = 9) with those of normal cycling women (n = 9). Frequent
      blood samples were obtained on postpartum day 5 or in the early follicular phase
      before and after administration of thyrotropin-releasing hormone (TRH) for serial
      determination of TSH and prolactin by immunoradiometric assay (IRMA). Based serum
      prolactin levels were high (p < 0.001) in lactating women and low in both non
      lactating and normal cycling women. When these differences in the basal prolactin
      concentrations were taken into account, the stimulated prolactin release
      (relative prolactin increase and area under the prolactin curve) was found to be
      highest (p < 0.05) in non-lactating women and lowest in lactating women. Basal
      TSH secretion was not significantly different between the groups of women (p >
      0.2). Yet, both the relative TSH increases and the response curves following TRH
      stimulations were high (p < 0.05) in normal cycling women and low in both
      lactating and non-lactating postpartum women. These observations confirm a
      difference in the basal and stimulated prolactin release between lactating and
      non-lactating women. They also indicate that the TRH-stimulated TSH release is
      greatly affected by the postpartum state, irrespective of lactation or
      therapeutic weaning. The observation of a decreased sensitivity of pituitary
      thyrotrophs in concert with unchanged basal TSH secretion is suggestive of
      changes in hypothalamic TRH secretion and/or in the TSH metabolic half-life
      during the postpartum period.

PMID- 8540288
TI  - Sex hormone-binding globulin and corticosteroid-binding globulin mRNA levels in
      infertile women with luteal phase deficiency.
AB  - This study was designed to investigate the biological significance in
      intracellular expression of sex hormone-binding globulin (SHBG) and
      corticosteroid-binding globulin (CBG) mRNA in uterine endometrium with luteal
      phase deficiency (designated as out-of-phase endometrium or low serum
      progesterone level). The levels of such mRNAs were measured by the quantitative
      reverse transcription-polymerase chain reaction. Under the normal serum 17 beta
      estradiol and progesterone levels in the mid-luteal phase, the levels of SHBG and
      CBG mRNAs in the out-of-phase endometria were not significantly different from
      those in the normal endometria. On the other hand, SHBG and CBG mRNA levels in
      the endometria of low serum midluteal progesterone level were significantly (p <
      0.05) reduced and raised, respectively, compared with normal levels. These
      findings suggest that the synthesis of endometrial steroid-binding proteins in
      the out-of-phase endometrium is conserved, as that in the in-phase endometrium,
      whereas the decreased progesterone level might up-regulate CBG expression with
      down-regulation of SHBG expression.

PMID- 8540287
TI  - A patient with a progesterone-producing adrenal adenoma who presented with
      primary amenorrhea.
AB  - A case report is presented of a patient with a primary amenorrhea due to a
      progesterone-producing adrenocortical adenoma. Clinical and endocrinological
      abnormalities disappeared after removal of the tumor, and the patient experienced
      her menarche. To our knowledge, a predominantly progesterone-producing adrenal
      adenoma--in this patient associated with the clinical picture of primary
      amenorrhea--has not previously been described.

PMID- 8540289
TI  - Timing of hCG administration in cycles stimulated for in vitro fertilization:
      specific impact of heterogeneous follicle sizes and steroid concentrations in
      plasma and follicle fluid on decision procedures.
AB  - The timing of ovulation induction is usually decided according to estradiol
      plasma concentrations and follicle size. We administered human chorionic
      gonadotropin (hCG) when at least three follicles of 16 mm or more in diameter and
      adequate estradiol plasma concentrations were detected. We studied the percentage
      of mature oocyte-cumulus-corona radiata complexes, estradiol and progesterone
      concentrations in a heterogeneous sized follicle population (range 10-20 mm, n =
      90) to perform a retrospective analysis of the adequacy of criteria adopted for
      the timing of ovulation induction. Plasma and follicular fluid were obtained from
      20 normo-ovulating women (aged 28-37 years) treated with gonadotropin releasing
      hormone analogs (GnRH-a) and human menopausal gonadotropin (hMG) for in vitro
      fertilization (IVF). No correlation was found between the mean individual
      follicular fluid estradiol concentration (500-5640 nmol/l) and the respective
      maximum concentration in plasma (2-16 nmol/l). The estradiol concentration was
      similar in all follicles. Total follicular fluid estradiol concentration was
      found to be correlated with follicular fluid volume (r = 0.771, p < 0.01). On the
      day of hCG administration, the concentration of estradiol in the plasma but not
      the follicular fluid was correlated with the number of oocyte-cumulus-corona
      radiata complexes collected (p < 0.01) and the number of mature complexes (p <
      0.01). At oocyte pick-up, the plasma concentration of progesterone was correlated
      (p < 0.01) with number of complexes collected and the number of mature complexes.
      The percentage of mature complexes collected (77.5%) was higher than suggested by
      the number of leading follicles. This indicates that our criteria for
      administering hCG were adequate and that heterogeneous follicle size does not
      exclude a high rate of mature oocyte-cumulus-corona radiata complexes.

PMID- 8540290
TI  - Comparison of androgen levels in conception vs. non-conception cycles following
      controlled ovarian stimulation using the luteal phase gonadotropin-releasing
      hormone agonist protocol.
AB  - Serum concentrations of androstenedione, testosterone and dehypdroepiandrosterone
      sulfate (DHEAS) as well as estradiol and progesterone were measured throughout
      the in vitro fertilization (IVF) cycle and compared by conception outcome to try
      to determine if differing levels of androgens could help elucidate the endocrine
      environment conducive to successful IVF cycles. The luteal phase gonadotropin
      releasing hormone agonist (GnRH-a) protocol was used for ovarian stimulation. of
      the 46 women enrolled in the study, 11 conceived and 35 did not conceive.
      Throughout the follicular phase, levels of androstenedione and DHEAS were found
      to rise but the same pattern of increase was found in both conception and non
      conception cycles. The pattern of testosterone increase in non-conception cycles
      was faster than that in conception cycles. Differences in mean levels of
      androstenedione, testosterone, estradiol and progesterone by conception outcome
      in the late luteal phase can be attributed to secretion by the corpus luteum. It
      is possible that those women having multiple failed cycles with rapidly rising
      serum testosterone levels should be considered for longer use of the GnRH-a.
      Differences in the pattern of testosterone rise should be monitored.

PMID- 8540291
TI  - Time-dependent changes in serum 3 alpha-androstanediol glucuronide correlate with
      hirsutism scores after ovarian suppression.
AB  - The clinical utility of serum 3 alpha-androstanediol glucuronide level has been
      controversial. Among the concerns regarding its lack of utility has been the
      finding that suppression of serum 3 alpha-androstanediol glucuronide does not
      occur readily with treatment. We hypothesized that because the treatment of
      hirsutism requires a prolonged duration, a longer observation period is required
      for changes in serum 3 alpha-androstanediol glucuronide to be measured.
      Therefore, we studied the clinical and hormonal changes in 11 women treated for
      hirsutism with a gonadotropin-releasing hormone agonist (GnRH-a) for 1 year. A
      progressive reduction in Ferriman-Gallwey scores occurred, which was significant
      at 6 weeks and was maximal at 12 months. Serum 3 alpha-androstanediol glucuronide
      and another peripheral marker, androsterone glucuronide, also fell
      commensurately. While there was no correlation at 3 months, by 6 weeks a
      significant correlation had occurred between the suppression in Ferriman-Gallwey
      scores and the suppression of serum 3 alpha-androstanediol glucuronide and
      androsterone glucuronide. The suppression of these steroids also correlated with
      the suppression of non-sex hormone-binding globulin-bound testosterone. These
      data confirm that markers of peripheral androgen action, particularly serum 3
      alpha-androstanediol glucuronide, reflect the clinical manifestation of
      hirsutism. However, it appears that modifications in peripheral androgen activity
      (presumably through 5 alpha-reductase activity) are time-dependent, and that
      serum markers reflect changes after 6 months of treatment.

PMID- 8540293
TI  - A contribution to the classification of cases of non-classic 21-hydroxylase
      deficient congenital adrenal hyperplasia.
AB  - The aim of this study was to classify the degree of 21 alpha-hydroxylase
      deficiency in patients suspected for non-classic 21-hydroxylase-deficient
      congenital adrenal hyperplasia (CAH). In 66 selected subjects (45 young women
      with polycystic ovary (PCO)-like symptoms and members of their families, of whom
      12 were men), progesterone, 17-hydroxyprogesterone (17-OHP) and cortisol were
      measured at 0, 15, 30, 45 and 60 min after adrenocorticotropic hormone (ACTH)
      stimulation. The markers [(17-OHP at 30 min--17-OHP at 0 min) + (progesterone at
      30 min--progesterone at 0 min)]/30 proposed by Gutai and the ratio of cortisol to
      17-OHP at 30 min (cortisol30/17-OHP30) were calculated and cluster analysis was
      performed using the above two markers and 17-OHP at 60 min (17-OHP60). Our
      patients were grouped by cluster analysis into four Groups: I, II, III and IV (n
      = 3, 11, 35 and 16, respectively) with (1) Gutai (mean +/- SE) 107.0 +/- 21.7,
      29.9 +/- 4.4, 10.5 +/- 0.54 and 4.0 +/- 0.37 ng/dl per min, respectively, (2) 17
      OHP60 169.7 +/- 28.3, 10.8 +/- 1.3, 4.6 +/- 0.2 and 3.7 +/- 0.4 ng/ml,
      respectively, and (3) cortisol/17-OHP30 0.97 +/- 0.28, 38.5 +/- 6.9, 82.3 +/- 5.5
      and 112.0 +/- 8.9, respectively. All three markers showed highly significant
      differences between the four groups (p < 0.0001). The patterns of 17-OHP,
      cortisol and cortisol/17-OHP ratio following ACTH testing revealed the degree of
      21-hydroxylase deficiency in every group. HLA typing effected in 20 studied
      individuals confirmed the classification derived from cluster analysis. Thus, it
      seems that Groups I, II and III include, respectively, patients with severe, mild
      and minimal forms of non-classic 21-hydroxylase-deficient CAH, while in patients
      of Group IV the hyperandrogenemic symptoms are of different etiology. In
      conclusion, the concurrent evaluation of the three markers together with the
      variations of 17-OHP, cortisol and the cortisol/17-OHP ratio after ACTH testing
      enhance the accurate identification of a patient suspected for non-classic 21
      hydroxylase-deficient CAH in relation to the severity of the enzymatic defect.

PMID- 8540292
TI  - Prolonged treatment of hirsutism with flutamide alone in patients affected by
      polycystic ovary syndrome.
AB  - Hirsutism is a common symptom of women affected by polycystic ovary syndrome
      (PCOS). The effectiveness of the antiandrogen flutamide alone was studied in 25
      patients affected by PCOS with severe hirsutism for a period of 24 months.
      Seventeen of these patients had not been treated before and eight had had
      previous but unsatisfactory therapy. Nineteen patients showed a normal body
      weight (BMI < 25 kg/m2) whereas six were obese (BMI > 35 kg/m2). A chemical and
      endocrinological evaluation and an assessment of the degree of hirsutism,
      assigned by Ferriman-Gallwey score (mean 22 +/- 3.038), was performed under
      baseline conditions. Patients started treatment with flutamide (Eulexin, Schering
      Plough, Kenilworth, USA) at the dose of 500 mg daily. A chronobiological
      assessment of gonadotropin episodic secretion and of gonadotropin response to
      GnRH challenge (10 micrograms in bolus) was done before and on day 7 of flutamide
      administration. During treatment, our patients showed a marked and significant
      reduction of hirsutism starting from a score of 6 and reaching the maximum (9.6 +
      2.1) at 24 months of therapy. No relevant hormonal changes or side-effects were
      observed during therapy. Our data demonstrate that hirsutism in PCOS can rapidly
      and markedly respond to treatment with flutamide alone without important side
      effects even if administered for a long period.

PMID- 8540294
TI  - Partial uncoupling of luteinizing hormone and prolactin pulse coincidence in
      hyperandrogenemic women.
AB  - A partly synchronized pulsatile secretion of luteinizing hormone (LH) and
      prolactin has previously been suggested as an indication of the coupling of the
      respective pulse generators under certain conditions. In women with
      hyperandrogenemic chronic anovulation, episodic LH secretion is disturbed. It
      was, therefore, the aim of the present study to evaluate possible changes in
      episodic prolactin secretion pattern and in LH/prolactin co-pulsatility, and to
      relate the results to the accelerated LH pulse frequencies often seen in patients
      with hyperandrogenemic chronic anovulation. Blood samples of 32 patients with
      hyperandrogenemia were taken at 10-min intervals between 10.00 and 20.00. Nine
      regularly cycling women with normal hormone levels served as controls. In the
      women with hyperandrogenemia, despite an average 41% rise of LH pulse frequency,
      prolactin pulse frequency decreased slightly by 14% as compared to controls; no
      correlation between the two parameters was found (r = 0.162). The number of
      coincident LH and prolactin pulses increased continuously with accelerating LH
      frequency. The best fitting function was a hyperbola which was limited by the
      maximal observed prolactin frequency. As a consequence, the fraction of LH pulses
      that were co-secreted with prolactin episodes decreased with higher LH pulse
      frequencies, while the fraction of prolactin pulses concomitant with LH pulses
      increased. Our data provide evidence that in women with hyperandrogenemic chronic
      anovulation a pathological LH pulse frequency is no longer coupled with pulsatile
      prolactin secretion, suggesting an isolated alteration of the central neuronal
      control mechanism for LH secretion.

PMID- 8540295
TI  - Hysterectomy increases the symptomatology of postmenopausal syndrome.
AB  - The purpose of our investigation was to verify whether or not women who have
      undergone hysterectomy react differently to the menopause compared with women who
      have not. The study was performed in a prospective documentation on 203 women,
      and the assessments of discomforts were provided by the patients themselves using
      questionnaires. For statistical purposes, the Mann-Whitney test and chi 2 test
      were used. In both groups of patients--with and without hysterectomy--a
      determination was made concerning the significance of differences in the degree
      of intensity of problems: breast tension (p < 0.05), muscle pains (p < 0.05),
      palpitations (p < 0.05) and dizziness (p < 0.01). Concerning the frequency of
      climacteric symptoms, a significant difference was noted for urogenital ailments.
      While only 29.6% of women who had not been operated on complained about
      discomfort caused by atrophy of the urogenital tract, the number of women with
      such discomfort who had had a hysterectomy was 42.6% (p < 0.01). In other words,
      women who underwent hysterectomy suffered more discomfort and showed frequent
      symptoms of urogenital atrophy.

PMID- 8540296
TI  - The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity:
      a prospective study using transvaginal color Doppler sonography.
AB  - The objective of this study was to correlate, during 12 weeks of therapy with
      gonadotropin releasing hormone agonist (GnRH-a), the chronological effect and the
      hemodynamic changes on the uterine artery and the leiomyometrial supplying
      vessels. Twenty-three premenopausal women with clinically diagnosed uterine
      leiomyomas received 3.75 mg of leuprolide acetate intramuscularly every 4 weeks
      for 12 weeks. Pretreatment values of serum estradiol, uterine and leiomyoma
      volumes and blood flow characteristics of the main uterine artery and leiomyoma
      supplying vessels-resistance index (RI), pulsatility index (PI) and peak-systolic
      velocity, obtained by transvaginal color Doppler sonography-were compared with
      treatment values at 4, 8 and 12 weeks of leuprolide acetate therapy. The first
      event in the chronological response to the GnRH-a therapy was a statistically
      significant increase in RI and PI values for major leiomyoma vessels, observed at
      the end of the 4th week (p < 0.05), which increased significantly after 8 and 12
      weeks (p < 0.01 and p < 0.001, respectively). These findings were in direct
      correlation with a significant decrease of estradiol levels after 4, 8 and 12
      weeks (p < 0.05, p < 0.001 and p < 0.001, respectively). The significant decrease
      of blood flow in the leiomyometrial vessels was followed by a significant
      decrease of the main uterine artery blood flow after 8 weeks and uterine and
      leiomyoma volumes by 42% and 55%, respectively, after 12 weeks of GnRH-a therapy.
      We concluded that a significant increase in leiomyometrial vessels RI and PI
      values, which was found 4 weeks after the first dose of GnRH-a, but without major
      leiomyoma volume decrease, emphasizes that the first significant effect of GnRH
      therapy in the process of uterine and leiomyoma volume shrinkage is the reduction
      of leiomyometrial rather than uterine blood flow. This effect is followed by a
      considerable reduction of uterine vascularity and a significant decrease of
      uterine and leiomyoma volumes. If a decrease of blood loss during myomectomy is
      the main aim of GnRH-a therapy, we believe that 8 weeks would be an appropriate
      therapy duration.

PMID- 8540297
TI  - The biological basis of medical treatment of endometriosis.
AB  - Efficacy of medical treatment for the management of endometriosis has been
      documented in several trials, but clinical results cannot always be maintained
      after the suspension of treatment. Surgical treatment, either laparotomic or
      laparoscopic, is affected by up to 20% in the recurrence of clinical symptoms
      after long-term follow-up. The appearance of endometriosis is heterogeneous, its
      functional status is variable and could lack hormone responsiveness. After
      medical, surgical or combined treatment the persistence of the failure of defence
      mechanisms accounts for the recurrence of disease. Unfortunately, all schemes to
      classify stages of endometriosis have so far failed to identify manifestations of
      the disease that respond in a predictable way to specific treatments. An analysis
      of the morphological appearance, implant biological activity and immune system
      involvement might better define the roles for medical management of
      endometriosis.

PMID- 8540298
TI  - Use of multivariate mathematical methods for the evaluation of retention data
      matrices.

PMID- 8540299
TI  - Emerging technologies for sequencing antisense oligonucleotides: capillary
      electrophoresis and mass spectrometry.

PMID- 8540300
TI  - Analysis of drugs of abuse in biological fluids by liquid chromatography.

PMID- 8540301
TI  - Electrochemical detection of biomolecules in liquid chromatography and capillary
      electrophoresis.

PMID- 8540302
TI  - The development and application of coupled HPLC-NMR spectroscopy.

PMID- 8540303
TI  - Microdialysis sampling for pharmacological studies: HPLC and CE analysis.

PMID- 8540304
TI  - Proceedings of the 5th International Conference on Aspartic Proteinases.
      Kawashimacho, Gifu Prefecture, Japan, September 19-24, 1993.

PMID- 8540305
TI  - Comparison of the active site specificity of the aspartic proteinases based on a
      systematic series of peptide substrates.

PMID- 8540306
TI  - Seminal progastricsin.

PMID- 8540307
TI  - Effects of hydrocortisone on the pepsinogen-producing cells in rat stomach
      mucosa.

PMID- 8540308
TI  - The molecular structure of human progastricsin and its comparison with that of
      porcine pepsinogen.

PMID- 8540309
TI  - Effects of omeprazole, a proton pump inhibitor, on pepsinogen-producing cells,
      with special reference to neonatal development.

PMID- 8540310
TI  - Transcription of embryonic chick pepsinogen gene is affected by mesenchymal
      signals through its 5'-flanking region.

PMID- 8540311
TI  - Serum pepsinogen values as possible markers for evaluating the possibility of
      peptic ulcer recurrence under H2-blocker half-dose maintenance therapy.

PMID- 8540312
TI  - The clinical application of the serum pepsinogen I and II levels as a mass
      screening method for gastric cancer.

PMID- 8540313
TI  - A minute gastric cancer detected by a new screening method using serum pepsinogen
      I and II.

PMID- 8540314
TI  - Two cases of early colorectal cancer associated with gastric adenoma detected by
      serum pepsinogen screening method.

PMID- 8540315
TI  - Comparisons of the three-dimensional structures, specificities and glycosylation
      of renins, yeast proteinase A and cathepsin D.
AB  - The crystal structures of complexes of the aspartic proteinases, human and mouse
      renins, yeast proteinase A and cathepsin D, with peptide analogue inhibitors are
      compared. Differences occur in the relative positions of the domain comprising
      residues 190-302 (pepsin numbering) compared to the remaining structure and in
      the nature and position of the irregular regions joining the beta-strands and
      alpha-helices. The first three of the five residues of the oligosaccharide
      structures attached to Asn 67 of yeast proteinase and cathepsin D cover the same
      region of the protein surface. All enzymes have an unusual, proline-rich region
      (292-297) which acts as a second flap (in addition to that involving residues 72
      81). This covers the active site cleft, but can be very close to the
      substrate/inhibitor at P3' and P4' only in the renins.

PMID- 8540316
TI  - Discovery of inhibitors of human renin with high oral bioavailability.
AB  - Knowledge of the sequence of a bioactive protein (angiotensinogen) and the
      availability of a natural product inhibitor lead (pepstatin) were the starting
      point for discovery of potent penta- and hexapeptide renin inhibitors. Study of
      the metabolism and disposition of these substances forced the discovery of
      simpler inhibitors leading to the discovery of oral activity in Terlakiren (22).
      Modification of physical properties led to the synthesis of aminopiperidine 30,
      which was identified by oral efficacy profiling. Structural modification to give
      enzymatic stability produced the bioavailable benzylsuccinate inhibitor 34. Its
      bioactive monomethylamine metabolite (35, CP-108,671) was subsequently found to
      have uniformly high oral bioavailability and activity in various species
      including primates.

PMID- 8540317
TI  - Structure of human cathepsin D: comparison of inhibitor binding and subdomain
      displacement with other aspartic proteases.

PMID- 8540318
TI  - A new way of looking at aspartic proteinase structures: a comparison of pepsin
      structure to other aspartic proteinases in the near active site region.

PMID- 8540319
TI  - Cathepsin D crystal structures and lysosomal sorting.

PMID- 8540320
TI  - Isolation and characterization of human gastric procathepsin E and cathepsin E.

PMID- 8540321
TI  - Isolation, characterization, and structure of procathepsin E and cathepsin E from
      the gastric mucosa of guinea pig.

PMID- 8540322
TI  - Cathepsin E and cathepsin D: biosynthesis, processing and subcellular location.

PMID- 8540323
TI  - Glycoproteins of the aspartyl proteinase gene family secreted by the developing
      placenta.
AB  - Pregnancy in cattle and sheep can be diagnosed by the presence of placentally
      derived antigens (pregnancy-associated glycoproteins or PAG-1) in maternal serum
      soon after implantation begins at about Day 20 following conception. Molecular
      cloning of their cDNA has revealed that PAG-1 belong to the aspartic proteinase
      gene family and have about 50% amino acid sequence identity to pepsin. However,
      critical amino acid substitutions at the active site regions suggest that both
      bovine and ovine PAG-1 are enzymatically inactive. PAG-1 expression has been
      shown by in situ hybridization and immunocytochemistry to be localized to the
      trophoblast binucleate cells, which invade maternal uterine endometrium during
      implantation. The glycoproteins are concentrated in dense cytoplasmic granules
      that are discharged after the binucleate cells have migrated to the maternal side
      of the placental barrier. We suggest, therefore, that the PAG-1 might have an
      endocrine function either as carriers of other bioactive peptides or by acting as
      hormones themselves. Recently screening of placental libraries with nucleic acid
      probes has identified additional cDNA that are very abundant and code for
      polypeptides (PAG-2 and PAG-3) related to, but antigenically and structurally
      distinct from PAG-1 described above. These molecules have sequences of amino
      acids at their catalytic centers that are consistent with their being potentially
      functional proteinases but their role during pregnancy, like that of PAG-1, is
      unclear.

PMID- 8540324
TI  - Structure and possible function of aspartic proteinases in barley and other
      plants.

PMID- 8540325
TI  - Aspartic proteinases (cyprosins) from Cynara cardunculus spp. Flavescens cv.
      cardoon; purification, characterisation, and tissue-specific expression.

PMID- 8540326
TI  - Acid-activation of rat prorenin following non-proteolytic alteration.

PMID- 8540327
TI  - Human procathepsin D: three-dimensional model and isolation.
AB  - Human procathepsin D was isolated from medium of human breast cancer cell line ZR
      75-1 potentiated with estrogen. The isolation involved both immunoaffinity
      chromatography and ion-exchange chromatography. The affinity chromatography
      employed polyclonal antibodies raised against a synthetic activation peptide of
      human cathepsin D. We have started preliminary crystallization trials using the
      isolated material. A model of human procathepsin D was also built using
      coordinates of human cathepsin D and pig pepsinogen. The model aids understanding
      of multiple roles played by activation peptides of aspartic proteinases and will
      be used as a starting model for molecular replacement.

PMID- 8540328
TI  - Identification of five molecular forms of cathepsin D in bovine milk.

PMID- 8540329
TI  - Site-directed mutagenesis of a disulfide bridge in cathepsin D: expression,
      activation, purification, and characterization.

PMID- 8540330
TI  - Expression of rat cathepsin D cDNA in Saccharomyces cerevisiae: intracellular
      sorting of cathepsin D to yeast vacuole.

PMID- 8540331
TI  - Molecular cloning and immunocytochemical localization of jasmonic acid inducible
      cathepsin D inhibitors from potato.

PMID- 8540332
TI  - Purification and characterization of an acid proteinase from Dirofilaria immitis
      worms.
AB  - An acid proteinase of Dirofilaria immitis worms was purified 437-fold by gel
      filtration on Sephadex G-75 followed by pepstatin-Agarose gel affinity
      chromatography. The enzyme with a molecular weight of 42 kDa was homogeneous as
      judged by both affinity chromatography and SDS-polyacrylamide gel
      electrophoresis. Polyacrylamide disc electrophoresis at pH 8.9, however, revealed
      that the enzyme was composed of five multi-forms, all carrying proteinase
      activity. Optimum pH of the enzyme was in the range of pH 2.8 to 3.4, and its
      isoelectric point ranged between 5.8 and 6.4. The purified proteinase showed a
      potent activity against hemoglobin and myoglobin releasing acid soluble peptides,
      but not free amino acids. When enzymatic properties of the proteinase was
      compared with mammalian cathepsin D and pepsin, D. immitis proteinase activity
      was reduced to about 80% of the initial activity by incubating at neutral pH and
      50 degrees C for 5 min, just like cathepsin D, which remained intact. Pepsin
      activity was completely destroyed under the same condition. An aspartic
      proteinase inhibitor, 1,2-epoxy-3-(p-nitrophenoxy)propane, which inhibited pepsin
      by 30% at 37 degrees C for 10 min, did show little effects on D. immitis
      proteinase and cathepsin D. Inhibitory effect of diazoacetyl-DL-norleucine methyl
      ester (DAN) on D. immitis proteinase was intermediate (50% after 60 min).
      Immunolocalization of the proteinase in the worm tissue using its monoclonal
      antibodies revealed that the enzyme was localized in the intestine as well as
      uterine wall and some small granules of microfilariae in the uterus.

PMID- 8540333
TI  - Inhibition and entrapment of aspartic proteinases by alpha 2-macroglobulin.

PMID- 8540334
TI  - Recombinant human cathepsin E.

PMID- 8540336
TI  - Purification and characterization of recombinant human cathepsin E.
AB  - The human cathepsin E was purified from the culture supernatant of Pichia
      pastoris strain transformed with a human cathepsin E expression plasmid.
      Purification was performed by a three-step procedure, TSKgel Phenyl-5PW,
      Toyopearl HW55S and TSKgel DEAE-5PW column chromatographies. The purified
      recombinant cathepsin E had the molecular mass of around 82-kDa with the amino
      terminal sequence started with Ile37 of the predicted amino acid sequence,
      suggesting the human cathepsin E was accumulated in the culture suparnatant as
      the mature dimer enzyme. The result of endoglycosidase-H digestion followed by
      Western blot analysis of the purified recombinant cathepsin E suggested that the
      human cathepsin E expressed in Pichia pastoris received N-linked high-mannose
      type glycosylation.

PMID- 8540335
TI  - Expression of human cathepsin E in methylotrophic yeast, Pichia pastoris.
AB  - The human gastric cathepsin E (CTSE) was expressed in the methylotrophic yeast
      Pichia pastoris by placing the CTSE cDNA under the control of the methanol
      inducible alcohol oxidase promoter. The human CTSE expressed in P. pastoris was
      efficiently secreted into the culture medium as an active enzyme directed by its
      native signal sequence, whereas CTSE has been shown to be retained in mammalian
      tissue cells. The recombinant human CTSE was secreted as a 90-kDa molecule and
      then converted via an 84-kDa intermediate to an 82-kDa molecule. The 90-kDa
      molecule and the 82-kDa molecule were considered to be the proenzyme and the
      mature enzyme as dimeric forms, respectively.

PMID- 8540337
TI  - Rearranging pepsinogen and pepsin by protein engineering.

PMID- 8540338
TI  - Comparison of biochemical properties of natural and recombinant cathepsin E.

PMID- 8540339
TI  - Increased expression and specific localization of cathepsins E and D in
      vulnerable brain regions of aged and postischemic rats.

PMID- 8540340
TI  - Characterization of cathepsins E and D accumulated at early stages of neuronal
      damage in hippocampal neurons of rats.

PMID- 8540341
TI  - Functional aspects of cathepsin E: is it an embryonic or fetal type of aspartic
      proteinase?

PMID- 8540342
TI  - Tissue- and cell-specific control of guinea pig cathepsin E gene expression.

PMID- 8540343
TI  - Cathepsin E is expressed in fetal rat glandular stomach epithelial cells in
      primary culture in the absence of mesenchymes.

PMID- 8540344
TI  - Cathepsin E expressed in pancreatic cancer.

PMID- 8540345
TI  - Plant aspartic proteinases from Cynara cardunculus spp. flavescens cv. cardoon;
      nucleotide sequence of a cDNA encoding cyprosin and its organ-specific
      expression.

PMID- 8540346
TI  - Cardosin A and B, aspartic proteases from the flowers of cardoon.

PMID- 8540347
TI  - Mechanism of autoprocessing of a mini-precursor of the aspartic protease of human
      immunodeficiency virus type 1.

PMID- 8540348
TI  - Mutants of HIV-1 protease with enhanced stability to autodegradation.

PMID- 8540349
TI  - Identification of amino acid residues of the retroviral aspartic proteinases
      important for substrate specificity and catalytic efficiency.

PMID- 8540350
TI  - Inhibitor-resistant mutants of the HIV-1 aspartic protease.

PMID- 8540351
TI  - Comparative investigations on pig gastric proteases and their zymogens.

PMID- 8540352
TI  - Design and synthesis of HIV protease inhibitors containing allophenylnorstatine
      as a transition-state mimic.

PMID- 8540354
TI  - X-ray structure of a tethered dimer for HIV-1 protease.

PMID- 8540353
TI  - Breaking the shackles of the genetic code: engineering retroviral proteases
      through total chemical synthesis.

PMID- 8540355
TI  - Structure of HIV-1 protease with KNI-272: a transition state mimetic inhibitor
      containing allophenylnorstatine.

PMID- 8540356
TI  - Molecular dynamics of HIV-1 protease in complex with a difluoroketone-containing
      inhibitor: implications for the catalytic mechanism.

PMID- 8540357
TI  - Activated dynamics of flap opening in HIV-1 protease.

PMID- 8540358
TI  - Computer simulation and analysis of the reaction pathway for the decomposition of
      the hydrated peptide bond in aspartic proteases.

PMID- 8540359
TI  - Activities of precursor and tethered dimer forms of HIV proteinase.

PMID- 8540360
TI  - Site-directed mutagenesis of HIV-1 protease: generation of mutant proteases with
      increased stability to autodigestion.

PMID- 8540361
TI  - Molecular modeling of the structure of FIV protease.

PMID- 8540362
TI  - Processing, purification, and kinetic characterization of the Gag-Pol encoded
      retroviral proteinase of myeloblastosis associated virus expressed in E. coli.

PMID- 8540363
TI  - Extracellular aspartic proteinases from Candida yeasts.

PMID- 8540365
TI  - Aspartic proteinases from the human malaria parasite Plasmodium falciparum.

PMID- 8540364
TI  - Tyrosine 75 on the flap contributes to enhance catalytic efficiency of a fungal
      aspartic proteinase, Mucor pusillus pepsin.

PMID- 8540366
TI  - Yeast and mammalian basic residue-specific aspartic proteases in prohormone
      conversion.

PMID- 8540367
TI  - Pepstatin-insensitive carboxyl proteinases.

PMID- 8540368
TI  - Non-mammalian vertebrate pepsinogens and pepsins: isolation and characterization.

PMID- 8540370
TI  - A quantum mechanical model of the hydration and acidity of the active site in
      aspartic proteases.

PMID- 8540369
TI  - The three-dimensional X-ray crystal structure of the aspartic proteinase native
      to Trichoderma reesei complexed with a renin inhibitor CP-80794.

PMID- 8540371
TI  - Site-directed mutagenesis of rhizopuspepsin: an analysis of unique specificity.

PMID- 8540372
TI  - Site-directed mutagenesis revealed role of subsite residues of Mucor pusillus
      pepsin in catalytic function.

PMID- 8540373
TI  - A novel intracellular acid proteinase from the plasmodia of a true slime mold,
      Physarum polycephalum.

PMID- 8540374
TI  - Characteristics of YAP3, a new prohormone processing aspartic protease from S.
      cerevisiae.

PMID- 8540375
TI  - Candida albicans aspartic proteinase: cDNA cloning and comparison among strains.

PMID- 8540376
TI  - Molecular cloning and sequence analysis of a gene encoding an aspartic proteinase
      from Aspergillus oryzae.

PMID- 8540377
TI  - Aspergillus niger var. macrosporus proteinase B. cDNA cloning, expression, and
      activation of the proenzyme.

PMID- 8540378
TI  - Expression and secretion of recombinant aspartic proteinases by Bacillus brevis.

PMID- 8540379
TI  - Expression in E. coli of Aspergillus niger var. macrosporus proteinase A, a non
      pepsin type acid proteinase.

PMID- 8540380
TI  - X-ray crystallographic study of a non-pepsin-type acid proteinase, Aspergillus
      niger proteinase A.

PMID- 8540382
TI  - Transcription regulation of human and porcine pepsinogen A.

PMID- 8540381
TI  - Conformation analysis of non-pepsin-type acid proteinase A from the fungus
      Aspergillus niger by NMR.

PMID- 8540383
TI  - A comparative study on amino acid sequences of three major isoforms of human
      pepsin A.

PMID- 8540384
TI  - Molecular mass determination by electrospray mass spectrometry of human pepsins,
      gastricsin, and porcine pepsin A variants.

PMID- 8540385
TI  - Evidence for electrostatic interactions in the S2 subsite of porcine pepsin.

PMID- 8540386
TI  - Protein engineering of surface loops: preliminary X-ray analysis of the CHY155
      165RHI mutant.

PMID- 8540387
TI  - Troponin C - troponin I interactions and molecular signalling in cardiac
      myofilaments.
AB  - This chapter describes a current perception of the molecular interactions
      regulating myofilament activity in heart cells. The focus is on the interaction
      between troponin-C (TnC), the Ca(2+)-receptor and troponin I (TnI), an inhibitory
      protein. It is this interaction that appears to form a molecular switch that
      turns on the thin filament. It will be seen that control of the actin-myosin
      reaction is not only through Ca(2+)-binding to TnC, but also through steric,
      cooperative and allosteric processes involving all of the main myofilament
      proteins-actin, myosin, tropomyosin (Tm), troponin T (TnT), TnC, and TnI. The
      process is modulated by covalent and non-covalent mechanisms. The process is
      altered in diverse myopathies and pathologies of the heart and is a target for
      pharmacological manipulation by a new class of inotropic agents, the "Ca(2+)
      sensitizers".

PMID- 8540388
TI  - Molecular mechanisms of K+ channel blockade: 4-aminopyridine interaction with a
      cloned cardiac transient K+ (Kv1.4) channel.
AB  - We studied the blocking effects of 4-aminopyridine (4-AP) on a Kv1.4 K+ channel.
      A permanently charged 4-AP derivative only produced block when applied
      intracellularly. 4-AP block accumulated from pulse to pulse indicating trapping
      of 4-AP in deactivated channels. For long trains of depolarizing pulses, 4-AP
      block increased with decreasing pulse duration. This increase took many pulses (>
      10) to accumulate and was relieved by two to three subsequent pulses of 500 msec
      duration. We conclude that the time- and voltage-dependence of 4-AP block can not
      be accounted for solely by either simple pure open channel or pure closed channel
      blocking schemes. We propose that the data can be explained by a model in which 4
      AP binding is most stable when the channel has a symmetric arrangement in the
      binding regions.

PMID- 8540389
TI  - The GATA-4 transcription factor transactivates the cardiac-specific troponin C
      promoter-enhancer in non-muscle cells.
AB  - The unique contractile phenotype of cardiac myocytes is determined by the
      expression of a set of cardiac-specific genes. By analogy to other mammalian
      developmental systems, it is likely that the coordinate expression of cardiac
      genes is controlled by lineage-specific transcription factors that interact with
      promoter and enhancer elements in the transcriptional regulatory regions of these
      genes. Here, we demonstrate that the slow/cardiac-specific troponin C (cTnC)
      enhancer contains a specific binding site for the lineage-restricted, zinc finger
      transcription factor, GATA-4 and that GATA-4 mRNA and protein is expressed in
      cardiac myocytes. In addition, GATA-4 binding sites were identified in several
      previously characterized cardiac-specific transcriptional regulatory elements.
      The cTnC GATA-4 binding site is required for transcriptional enhancer activity in
      primary cardiac myocytes. Moreover, the cTnC enhancer can be transactivated by
      over-expression of GATA-4 in non-cardiac muscle cells such as NIH 3T3 cells.
      Taken together, these results are consistent with a model in which GATA-4
      functions to direct tissue-specific gene expression during mammalian cardiac
      development.

PMID- 8540391
TI  - Crossbridge dynamics in muscle contraction.
AB  - The study deals with the description of muscle contraction based on biochemical
      studies and describes four major approaches for coupling calcium kinetics with
      crossbridge (Xb) cycling. The analysis illuminates two controversial points: 1)
      the relationship between Xb attachment/detachment and Xb cycling, i.e., the
      transition between weak to strong conformations, and 2) the effect of calcium on
      Xb function: does it regulate Xb kinetics or Xb recruitment.

PMID- 8540390
TI  - Sarcomere function and crossbridge cycling.
AB  - The power of the heart is dictated by the force development and velocity of
      shortening (V) of the cardiac sarcomere. Both depend on the amount of Ca++
      released by the sarcoplasmic reticulum during the action potential. We have
      investigated the inter-relationship between force (F) sarcomere length (SL) and V
      and the intracellular Ca++ concentration ([Ca++]i) in trabeculae isolated from
      the right ventricle of rat heart. Activation of the contractile filaments during
      a normal heartbeat requires approximately 30 microM Ca++ ions, which rapidly bind
      to cytosolic ligands. Consequently the [Ca++]i transient detected by
      intracellular probes is less than 2 microM. Length dependent binding of Ca++ to
      Troponin-C is responsible for the shape of the F-SL relationship. Ca++ ions are
      bound to Troponin-C long enough to allow the F-SL relationship, and consequently
      the end-systolic pressure volume relationship in the intact ventricle, to be
      largely--but not completely--independent of the loading conditions. V increases
      hyperbolically with decreasing load during contraction against a load. Stiffness
      studies reveal that the number of attached crossbridges increases in linear
      proportion to an increase of the external load. At low external loads the V was
      large enough to induce a substantial viscoelastic load within the sarcomere
      itself. The F-V relationship of a single crossbridge appeared to be linear after
      correction for the observed viscoelastic properties of the muscle and for load
      dependence of the number of crossbridges. Maximal V of sarcomere shortening
      without an external load (Vo), depends on the level of activation by Ca++ ions
      because of the internal viscous load. Our studies of the rate of ATP hydrolysis
      by the actin-activated S1 fragment of myosin suggest that Vo is limited by the
      detachment rate of the crossbridge from actin. These studies also suggest that
      the difference between the fast (V1) and slow (V2) myosin iso-enzyme can be
      explained by a difference in the amino acid domain on S1 involved in binding of
      the crossbridge to the actin filament.

PMID- 8540392
TI  - Mechanisms of the Frank-Starling phenomena studied in intact hearts.
AB  - The impact of ventricular volume on the relationship between intracellular
      calcium and ventricular pressure under steady-state conditions was determined in
      intact ferret hearts. The results reveal major quantitative differences and minor
      qualitative differences between these relations and those previously measured in
      isolated intact and skinned cardiac muscle. The importance of these differences
      is discussed within the context of developing a comprehensive mechanistic theory
      to describe load-dependence of the intact ventricle.

PMID- 8540393
TI  - Metabolic oscillations in heart cells.
AB  - Oscillatory rhythms underlie biological processes as diverse and fundamental as
      neuronal firing, secretion, and muscle contraction. We have detected periodic
      changes in membrane ionic current driven by intrinsic oscillations of energy
      metabolism in guinea pig heart cells. Withdrawal of exogenous substrates
      initiated oscillatory activation of ATP-sensitive potassium current and cyclical
      suppression of depolarization-evoked intracellular calcium transients. The
      oscillations in membrane current were not driven by pacemaker currents or by
      alterations in intracellular calcium and thus represent a novel cytoplasmic
      cardiac oscillator. The linkage to energy metabolism was demonstrated by
      monitoring oscillations in the oxidation state of pyridine nucleotides.
      Interventions which altered the rate of glucose metabolism modulated the
      oscillations, suggesting that the rhythms originated at the level of glycolysis.
      The metabolic oscillations produced cyclical changes in electrical excitability,
      underscoring the potential importance of this intrinsic oscillator in the genesis
      of cardiac arrhythmias.

PMID- 8540394
TI  - Altered gene transcription following brief episodes of coronary occlusions.
AB  - This study was designed to elucidate whether previously observed enhanced mRNAs
      were due to accelerated transcription, enhanced mRNA stability or both
      mechanisms. We employed the nuclear run-on technique on myocardial nuclei and
      found the transcriptional induction of several genes, especially nuclear
      protooncogenes, Ca2+ regulating and heat shock protein genes.

PMID- 8540395
TI  - Mechanoperception and mechanotransduction in cardiac adaptation: mechanical and
      molecular aspects.
AB  - Cardiomyocytes grow in hypertrophy due to a net increase in the synthesis of
      proteins, especially contractile proteins, in the cell. There is abundant
      information about the molecular and biochemical changes involved in this process,
      but it is not completely understood how cells sense mechanical stimuli and how
      these stimuli are transferred into a biochemical signal inducing the growth
      response. This mechanotransduction most likely takes place at the cellular
      membrane. The resulting signal is transferred to the nucleus, where it can
      initiate alterations in gene expression.

PMID- 8540396
TI  - Molecular manifestations of cardiac hypertrophy in the spontaneously hypertensive
      rat effects of antihypertensive treatments.
AB  - Antihypertensive treatments were given to young and adult SHRs, to prevent and
      reverse hypertension, respectively. Cardiac hypertrophy and the steady state
      level of the "fetal" genes, ANP, alpha-skeletal actin (alpha-skA), and beta
      myosin heavy chain (beta-MHC) mRNAs were assessed. Our findings show that the
      reduction of blood pressure does not consistently result in a similar regression
      of the "fetal gene program".

PMID- 8540397
TI  - Regulation of adenosine receptors in cultured heart cells.
AB  - A1 adenosine receptors were studied on heart cells grown in cultures by the
      radioligand binding technique. Treatments with agents that accelerated heart rate
      for 3-4 days, caused an increase in the level of adenosine receptors. Treatments
      that attenuated heart rate, reduced the level of the receptors. Thus, the cardiac
      cells respond to environmental conditions affecting heart contraction so as to
      restore the basal rate of heart activity.

PMID- 8540398
TI  - A model approach to the adaptation of cardiac structure by mechanical feedback in
      the environment of the cell.
AB  - The uniformity of the mechanical load of the cardiac fibers in the wall is
      maintained by continuous remodeling. In this proposed model the myocyte changes
      direction in optimizing systolic sarcomere shortening. Early systolic stretch and
      contractility increases the mass of contractile proteins. Cyclic strain of the
      myocardial tissue diminishes passive stiffness, resulting in the control of
      ventricular end-diastolic volume. Utilizing these rules of remodeling in our
      mathematical model yields that the natural helical pathways of the myocardial
      fibers in the wall are formed automatically.

PMID- 8540399
TI  - The effect of cytotoxic lymphocytes on contraction, action potential and calcium
      handling in cultured myocardial cells.
AB  - Cytotoxic T lymphocytes are important in the pathogenesis of several disease
      states, yet the pathophysiology of the lymphocyte-myocyte interaction is not well
      known. We have developed in vitro viral and autoimmune models to study the
      physiological phenomena associated with this interaction. To produce these
      models, lymphocytes were obtained from adult rats injected either with mengo
      virus or autologous cardiac myocytes. Cardiac myocytes from neonatal rats were
      then exposed to these lymphocytes. In both models, reversible physiologic changes
      in myocytes preceded irreversible cell damage. The physiologic changes included
      reduced amplitude of myocyte contraction, impairment of relaxation and
      prolongation of the duration of contraction and action potential. In addition,
      oscillations were noted in the plateau phase of the action potentials. These
      physiologic changes were accompanied by an early elevation in the cytosolic free
      calcium concentration, a late elevation in the total exchangeable calcium pool,
      and attenuation of the [Ca2+]i transient signals. Verapamil inhibited the late
      elevation in the total exchangeable calcium pool, but failed to inhibit the early
      elevation in the cytosolic free calcium concentration. These phenomena may
      explain transient cardiac functional abnormalities that may appear during
      myocarditis prior to cell destruction.

PMID- 8540400
TI  - Na+, K(+)-ATPase and heart excitability.
AB  - The Na+, K(+)-activated adenosine triphosphatase (ATPase) is present in the
      membrane of eukaryotic cells and represent a major pathway for Na+ and K+
      transport across the plasma membrane. Cardiac glycosides, such as digoxin or
      ouabain, inhibit this enzyme activity by binding to a specific receptor on the
      membrane. Studies conducted in this and other laboratories have proven the
      existence of digitalis-like compounds in animal and human tissues which may serve
      as regulators, in vivo, of the Na+, K(+)-pump activity. The levels of digitalis
      like compounds in the plasma are increased in hypertension and other illnesses. A
      possible link at the cellular and molecular level between these compounds and
      etiology of arrhythmias, an important cause of morbidity and mortality in
      patients with various diseases of the heart, can be postulated: Na+, K(+)-ATPase
      activity contributes directly and indirectly to the electrical membrane potential
      of cardiac cells. The inhibition of this pump by the endogenous digitalis-like
      compounds, in discrete areas of the heart, can induce changes of the membrane
      potential of these cells. These changes may cause an increase in excitability of
      the particular cells and contribute to the generation of arrhythmias.

PMID- 8540401
TI  - Ventricular remodeling in heart failure: the role of myocardial collagen.
AB  - Collagen which is present in the myocardium in relatively small amounts is the
      most abundant structural protein of the connective tissue network. Its structural
      organization consists of a complex weave of collagen fibers that surrounds and
      interconnects myocytes, groups of myocytes, muscle fibers and muscle bundles. The
      conformation of interstitial fibrillar collagen makes it highly resistant to
      degradation by all proteinases other than specific collagenases. In hearts with
      myocardial damage secondary to myocardial infarction, chronic ischemia,
      inflammation, or cardiomyopathy, a complex sequence of compensatory events occur
      that eventually result in an adverse left ventricular remodeling. This continual
      state of remodeling is characterized by persistent collagenase activity,
      fibrillar collagen degradation, and progressive myocyte loss. The net effect is a
      shift in the balance between collagen synthesis and degradation which leads to an
      inadequate fibrillar collagen matrix, progressive ventricular dilatation and
      sphericalization with wall thinning and eventual congestive heart failure.

PMID- 8540402
TI  - Mechanisms of endocardial endothelium modulation of myocardial performance.
AB  - The endocardial endothelium (EE) modulates the performance of the subjacent
      myocardium and plays an important role in regulation of cardiac function. This
      modulation has been confirmed in a number of different species and in both in
      vitro and in vivo conditions. The mechanisms of EE modulation of myocardial
      performance are still under investigation and the possibilities include the role
      of EE as a transendothelial physico-chemical barrier and/or the release of
      various chemical messengers by the EE.

PMID- 8540403
TI  - Myocardial microcirculation as evaluated with CT.
AB  - This study explores use of whole-body CT imaging to separately quantitate the
      physiological behavior of the nonrecruitable (e.g., arterioles) and recruitable
      (mostly capillary) components of the intramyocardial microcirculation. In two
      groups of dogs, one with microembolization and one with epicardial artery
      stenosis, we demonstrate that intramyocardial blood volume (rho) and blood flow
      (F) follow the relationship rho = AF + BF1/2 where A represents the transit time
      of the recruitable and BF-1/2 is the transit time of the nonrecruitable
      components. These transit times are shown to change in different, but
      characteristic, patterns.

PMID- 8540404
TI  - Vascular gene therapy.
AB  - Gene therapy is emerging as a new and exciting therapeutic modality for
      cardiovascular pathology. The work reported here was carried out in the National
      Heart, Lung and Blood Institute (NHLBI) in Bethesda, MD, USA, where genetically
      engineered endothelial cells were used to seed endovascular prostheses and cell
      adhesion to the prostheses was tested both in vitro and in vivo. Two catheter
      based systems were used to deliver genes to the arterial wall cells in vivo,
      employing retroviral and adenoviral vectors. Efficient gene transfer to vascular
      cells in vivo was achieved with adenoviral vectors.

PMID- 8540405
TI  - Integration of structure, function and mass transport in the myocardium.
AB  - A left ventricular (LV) model that integrates muscle mechanics, coronary flow,
      and fluid transport, and accounts for the three-phase (fiber-blood-interstitium)
      myocardial structure and composition, is used to study the interactions between
      the mechanics, coronary flow and fluid and mass transport in the myocardium.
      Theoretical simulations elucidate the effects of ventricular load, coronary
      perfusion pressure, and fluid and mass transport on ventricular performance and
      coronary dynamics. The analysis yields a direct relation between cardiac function
      and structure to cardiac mechanics, coronary flow, and intramyocardial fluid (and
      mass) transport, and allows to study the interactions between coronary flow,
      ventricular and myocardial mechanics and intramyocardial fluid shifts.

PMID- 8540406
TI  - Hypertrophic cardiomyopathy: functional aspects by tagged magnetic resonance
      imaging.
AB  - Studies addressing the issue of regional function in hypertrophic cardiomyopathy
      patients (HCM) are reviewed. The relationship between regional wall thickness and
      function in these patients was studied by three dimensional (3D) tagged magnetic
      resonance imaging (MRI) utilizing the volume-element approach. Regional function
      was indexed by myocardial thickening and circumferential shortening and related
      to the local thickness and wall stress index. An inverse relationship was found
      between wall thickening and thickness as well as between circumferential
      shortening and wall thickness. Lower stresses were obtained for thicker
      myocardial segments. Function of the normal-thickness regions was enhanced in the
      HCM patients relative to the normal subjects. Thicker segments in patients with
      HCM are thus characterized by reduced systolic function, which occurs at segments
      with relatively low stress levels. This pattern is consistent with the hypothesis
      that the thick myocardial segments have reduced contractile activity, probably
      due to recently identified mutations in the gene responsible for production of
      beta heavy chain myosin as well as other contractile proteins.

PMID- 8540407
TI  - Ion channels and pumps in cardiac function.
AB  - Ion channels and pumps are intrinsic membrane proteins that regulate the membrane
      potential and transport of ions and substrates, controlling excitation and
      excitation-contraction coupling. Several have been cloned and an example of our
      progress in structure-function correlation is the identification of the pore
      region of the Na channel.

PMID- 8540408
TI  - Myocardial constitutive laws for continuum mechanics models of the heart.
AB  - Myocardial constitutive laws, for use in anatomically accurate finite element
      models of the heart, are presented for the passive and active mechanical
      properties of cardiac muscle. Biaxial testing of tissue sheets together with
      observations of tissue microstructure are used to define a "pole-zero" strain
      energy function for passive myocardium. A "fading memory" model of actively
      developed tension is based here on published work on the active properties of
      cardiac trabeculae.

PMID- 8540409
TI  - Excitation-contraction coupling in ventricular myocytes: effects of angiotensin
      II.
AB  - The effects of the vasoactive peptide angiotensin II (AII) on contractility and
      excitation-contraction coupling in isolated adult rabbit ventricular myocytes
      were investigated. In most ventricular myocytes, AII (10(-8) M) induced a
      significant increase in fractional shortening which was not associated with an
      increase in the calcium transient measured with indo-1. AII did increase the
      intracellular pH by approximately 0.2 5 pH units coincident with the positive
      inotropic effect. Effects of AII on pH and contractility were blocked by
      inhibitors of Na+/H+ exchange. AII also increased the rate of pHi recovery from
      intracellular acidosis at pHi values above 6.9. AII was shown not to affect the L
      type inward calcium current. However, in an occasional cell, AII was observed to
      cause a slight increase in the calcium transient. We hypothesize that this
      response may reflect an increase of calcium influx on the sodium calcium
      exchanger, as a consequence of an increase in subsarcolemmal sodium concentration
      resulting from enhanced Na(+)-H+ exchange.

PMID- 8540410
TI  - Distribution of myocardial strains: an MRI study.
AB  - Quantification of myocardial strains is essential for understanding cardiac
      mechanics. Previous techniques for assessing regional myocardial strains have
      been mainly limited to invasive procedures. A technique by which tagging can be
      added to magnetic resonance images (MRI) has recently been introduced and allows
      for noninvasive measurement of myocardial deformations. We have applied MRI
      tagging to two sets of orthogonal planes and have obtained three dimensional (3D)
      reconstructions of 24 myocardial cuboids at end-diastole (ED) and at end-systole
      (ES). Applying finite strain analysis to these cuboids we were able to study the
      longitudinal distribution of the endocardial and epicardial principal strains
      (PS) in the normal canine heart. In addition we have calculated the longitudinal
      distribution of the left ventricular (LV) transmural thickening using a 3D
      approach. Our results show similarity in the longitudinal distribution of
      endocardial PS and transmural thickening. These results imply that endocardial
      strains are determined not only by endocardial fiber deformations but mainly by
      geometrical coupling through transmural thickening.

PMID- 8540411
TI  - Toward modeling the human physionome.
AB  - The physionome is the description of the physiological dynamics of the normal
      intact organism. The march of science brings us now into the era where
      integration of the various facets of the knowledge of biology and medicine has
      become a major issue. Modeling is a vehicle for the combining of information from
      molecular biology, biophysics, and medical biology, but must be combined with
      strategies for databasing the raw data with greater efficiency than is currently
      possible. The lessons from the genome project can be applied to the next level
      major projects, the morphonome and the physionome, the objective being to put
      integrated forms of the data into the hands of physicians and medical scientists.

PMID- 8540412
TI  - Prospects for genetic manipulation of cardiac excitability.
AB  - Despite impressive advances in the therapy of a number of types of heart disease
      in the last two decades, sudden cardiac death remains a public health problem of
      staggering dimensions. Current treatment options include antiarrhythmic drugs
      that have higher than desired failure rates and implantable defibrillators that
      incur significant costs to the patient and society. The development of therapies
      that better suppress the cardiac arrhythmias responsible for sudden cardiac death
      requires a broad and comprehensive understanding of the basic mechanisms
      underlying electrical instability in the heart. This study explores the
      scientific basis for a molecular genetic approach to modify cardiac excitability
      and thereby to create animal models of sudden cardiac death. The availability of
      such models will open up new avenues of research in arrhythmogenesis and
      facilitate the development of novel antiarrhythmic agents.

PMID- 8540413
TI  - Integrative models and responses in cardiac ischemia.
AB  - This chapter considers the study of electrophysiological changes during ischemia
      and incorporates mechanoelectric feedback, i.e., mechanical changes affecting
      electrophysiology. It considers these interactions in the cell, through multicell
      systems, the intact heart and the intact organism.

PMID- 8540414
TI  - Rich dynamics in a simplified excitable system.
AB  - The study aims at exploring effects of microscopic channel fluctuations on
      macroscopic dynamics of excitable systems. Molecular biology techniques are used
      in order to construct a minimal excitable system that is built of cloned channels
      embedded in a small (approximately 1 micron 2) isolated patch of membrane. This
      simple synthetic "point" system exhibits dynamics in time scales that are several
      orders of magnitude longer then a single spike.

PMID- 8540415
TI  - Model studies of cellular excitation.
AB  - A mathematical model of the cardiac ventricular cell is used to describe ionic
      currents and dynamic concentration changes during a normal action potential. The
      model is also used to study arrhythmogenic activity of the single cell including
      early afterdepolarizations, delayed afterdepolarizations and rhythmic
      (spontaneous and triggered) activity under various degrees of calcium overload.

PMID- 8540416
TI  - Confocal microscopy reveals local SR calcium release in voltage-clamped cardiac
      cells.
AB  - Confocal microscopy during voltage-clamp depolarization of mammalian heart cells
      revealed distinct local [Ca2+]i-transients that resulted from Ca2+ released
      through sarcoplasmic reticulum (SR) release channel(s). When voltage was varied,
      the latency to occurrence and the relative probability of local [Ca2+]i
      transients varied as predicted if SR Ca(2+)-release is linked tightly to Ca2+
      flux through co-associated L-type Ca(2+)-channels.

PMID- 8540417
TI  - Signaling of Ca2+ release and contraction in cardiac myocytes.
AB  - Cross signaling between Ca2+ channel and ryanodine receptor was explored in whole
      cell clamped rat ventricular myocyte under conditions where global myoplasmic
      Ca2+ concentrations were strongly buffered by dialyzing the myocytes with high
      concentrations of Fura 2 and EGTA. Ca2+ channel and ryanodine receptor were
      respectively activated by a depolarizing pulse to -10 mV and rapid (< 50 ms)
      application of 5 mM caffeine. Temporal analysis of kinetics of inactivation of
      Ca2+ channel with respect to the time of application of caffeine pulse provided
      experimental evidence that signalling between the ryanodine and Ca2+ channel is
      mediated exclusively through the Ca2+ microdomains surrounding the DHP/ryanodine
      receptor complex independent of global myoplasmic Ca2+ concentrations.

PMID- 8540418
TI  - A model of Ca2+ release from the sarcoplasmic reticulum.
AB  - Various functions in the myocyte depend on Ca2+ transport, yet the control of
      these processes is still obscure. In order to better understand the intracellular
      Ca2+ processes, a model of Ca2+ release from the cardiac sarcoplasmic reticulum
      (SR) is suggested, in which the release of Ca2+ from the SR is mainly regulated
      by the kinetics of Ca2+ channels within the SR membrane. These kinetics are
      controlled by changes in the concentration of free Ca2+ near the openings of Ca2+
      channels, and are affected by Ca2+ competitors, e.g., ryanodine. The control
      mechanism is based on a combination of positive and negative control loops,
      associated with two respective types of Ca2+ binding sites located on the SR
      membrane: 1) activating sites with low affinity to Ca2+ and high binding rate,
      and 2) inactivating sites with high affinity but low binding rate. The model also
      assumes that the activation of the Ca2+ channels depends on the preceding
      stimulation pattern (short term memory), an additional activation mechanism which
      is Ca2+ independent. This report describes the cytoplasmatic Ca2+ concentration
      in response to Ca2+ release from the SR, including the dependence on the beat
      intervals, either in the steady state or during response to premature and delayed
      beats. The analysis of ryanodine intervention supports a control mechanism based
      on two feedback loops, and available interval-dependent data favors inclusion of
      the short-term memory mechanism in the proposed model.

PMID- 8540419
TI  - Cellulose hydrolysis by bacteria and fungi.

PMID- 8540420
TI  - Cationic bactericidal peptides.

PMID- 8540421
TI  - Methylglyoxal and regulation of its metabolism in microorganisms.

PMID- 8540422
TI  - Molecular responses of microbes to environmental pH stress.

PMID- 8540423
TI  - Osmoadaptation in bacteria.

PMID- 8540424
TI  - Calcium and bacteria.

PMID- 8540425
TI  - Hypoxic and ischemic central nervous system disorders in infants and children.
AB  - Brain damage from severe hypoxemia and ischemia is involved in many childhood
      disorders that produce permanent disability. Recent progress in diagnosis and
      brain imaging as well as in the laboratory has expanded understanding of the
      pathophysiology of these disorders. They are currently thought to trigger a
      neurotoxic biochemical cascade that produces permanent cell death over a period
      of hours to days. A prominent feature of this cascade is synaptic dysfunction and
      overactivation of excitatory amino acid receptors that carry a majority of the
      excitatory messages transmitted in the brain. In premature infants the
      periventricular white matter is especially vulnerable, whereas neuronal
      structures are more vulnerable at term and at older ages. Numerous drugs are now
      known to protect the brain from neuronal damage in laboratory models. Application
      of this new pharmacology will require techniques to monitor cerebral metabolism
      and blood flow at the bedside in order to ensure that only high-risk infants are
      included. Although the new medications can be expected to have significant
      adverse effects as well as benefits, it seems likely that this therapy will be
      applied to certain high-risk groups over the next decade.

PMID- 8540426
TI  - Congenital adrenal hyperplasia: molecular genetics and alternative approaches to
      treatment.

PMID- 8540427
TI  - Gene expression in the intestine: the effect of dietary nucleotides.
AB  - There is scientific concern regarding the role of dietary nucleotides in the
      maintenance and repair of the gastrointestinal tract. This concern is based on a
      growing body of research that demonstrates potential mechanisms for dietary
      nucleotides to affect intestinal development and turnover. It seems clear that
      intestinal gene transcription as well as the activity of transcription factors is
      at least sometimes directly related to nutrition. Implications of this work
      include the potential role of dietary nucleotides in infant nutrition and in
      intestinal repair. The techniques of molecular biology will now allow us to
      explore and explain how dietary factors such as nucleotides affect intestinal
      mucosal development, function, adaptation, and repair.

PMID- 8540428
TI  - Human milk and intestinal host defense in newborns: an update.
AB  - In this update of the role of breast milk ingestion on passive and active
      protection of the human neonate, new observations and studies are presented that
      appear to support the concept that preterm and term infants should receive their
      mother's milk so far as possible. New objective evidence has been presented to
      support the role of breast milk in the protection of the newborn from intestinal
      and systemic infections. New concepts of the active role of breast milk growth
      factors on an accelerated development of the infant's own mucosal barrier
      function are presented, as well as preliminary data to support the role of breast
      milk growth factors in gut development. This new area of breast milk function,
      however, requires extensive clinical studies to support the practical value of
      breast milk in the development of the infant's own defenses.

PMID- 8540429
TI  - Carnitine disorders.

PMID- 8540430
TI  - Oxyradical pathophysiology.

PMID- 8540432
TI  - Hyperbaric oxygen therapy in pediatrics.

PMID- 8540431
TI  - Carbon monoxide and carboxyhemoglobin.

PMID- 8540433
TI  - Nitric oxide in the developing lung.

PMID- 8540434
TI  - Update on pediatric movement disorders.

PMID- 8540435
TI  - Sports injuries in young athletes.
AB  - Injuries to a skeletally immature athlete are common, but most of the injuries do
      not have long-term implications. There is no risk-free sport, and children tend
      to select the sports they wish to participate in based on their own desire, peer
      pressure, and their own talent regardless of the injury rate. Both acute and
      overuse injuries may occur. Open physes and apophyses represent unique structures
      that may be injured in this population. Prompt and proper identification of many
      of these injuries may allow the young athlete a relatively timely return to
      sports competition or recreation. Pediatricians and other primary care providers
      can make an active commitment to youth sports by learning more about these common
      sports-related injuries and becoming team physicians or joining local sports
      medicine advisory councils.

PMID- 8540436
TI  - Critical care of children with acute brain injury.
AB  - Severe neurologic illness and injury in children may occur in a wide range of
      clinical and environmental settings. The majority of children who sustain
      traumatic brain injury will achieve a good outcome if intensive care is directed
      toward preventing secondary injury. The most important aspect of care is ensuring
      adequate oxygenation, ventilation, and perfusion. Together with standard
      supportive care, the aggressive use of intraventricular pressure monitoring and
      CSF drainage to treat intracranial hypertension can attenuate or prevent
      continuing brain injury. Sustained hyperventilation, aggressive diuresis,
      hypothermia, and induction of barbiturate coma are reserved for children for whom
      the first tier of therapy is not effective.

PMID- 8540437
TI  - Management of pediatric limb length inequality.
AB  - The treatment of limb length inequality in pediatric patients is a complicated
      and long-term procedure, and careful evaluation is necessary over several visits.
      A team approach with an involved family is essential, as is knowledge and
      familiarity with the various conservative and surgical options. Treatment must
      not be rushed, and it is important to realize that not everyone needs a
      lengthening. Soft tissue and osseous complications are significant in these
      procedures, so shoe lifts and shortening procedures are attractive alternatives
      in smaller discrepancies. This condition is in a growing child and therefore not
      static. Future growth may dictate that procedures be staged. Most importantly, we
      must carefully equalize limb length in a manner that is neither physically nor
      emotionally scarring (Fig 26). These children are best served by a well-thought
      out plan that minimizes both kinds of trauma, decreases hospital and treatment
      time, and involves the family and patient in the planning and understanding of
      the proposed intervention and potential complications.

PMID- 8540438
TI  - Growth and its assessment.

PMID- 8540439
TI  - Unilateral renal agenesis.
AB  - Unilateral renal agenesis is a relatively common congenital urinary malformation
      that is usually diagnosed during fetal ultrasonography. Some cases of URA may
      represent involution of a previous MCDK. Unilateral renal agenesis may be an
      isolated congenital malformation or may be associated with chromosomal
      abnormalities or a variety of nonchromosomal syndromes including the VACTERL and
      MURCS associations. Congenital cardiac malformations are the most common
      malformations associated with URA. Girls with URA should have a pelvic ultrasound
      to look for abnormalities in the mullerian structures. Vesicoureteral reflux is
      the most common abnormality noted in the contralateral kidney. The prognosis of
      individuals with isolated URA is good. There are reports of hypertension and
      renal insufficiency in long-term studies of patients with a single kidney, and
      lifetime follow-up is recommended.

PMID- 8540440
TI  - Advances in pediatric pharmacology and toxicology.

PMID- 8540441
TI  - New mechanisms for genetic disease and nontraditional modes of inheritance.

PMID- 8540442
TI  - British Geriatrics Society spring meeting. Torquay, 6-8 April 1995. Abstracts.

PMID- 8540443
TI  - Psychological determinants of anginal pain perception during exercise testing of
      stable patients after recovery from acute myocardial infarction or unstable
      angina pectoris.
AB  - The objective of this study was to test the hypothesis that psychological factors
      are determinants of anginal symptoms during positive exercise tests. The sample
      consisted of clinically stable patients who were enrolled in the Multicenter
      Study of Myocardial Ischemia 1 to 6 months after admission to a coronary care
      unit. Among 186 post-myocardial infarction patients, 151 developed ischemia
      (i.e., a stress-induced myocardial perfusion defect) without symptoms (silent
      ischemia) and 35 developed angina with ischemia (symptomatic ischemia) during a
      thallium exercise test; among 39 patients who had been hospitalized for unstable
      angina, 24 developed silent ischemia and 15 developed symptomatic ischemia. Two
      sets of psychometric tests were administered: set 1, factors that influence
      awareness of physical symptoms, and set 2, factors associated with biases toward
      or against reporting perceived symptoms. Two hundred eleven patients produced
      complete data in each set. Analysis of set 1 factor scores revealed significant
      effects of symptom status (p = 0.006) and index event (p = 0.02), but no
      interaction. No effects were found in set 2. Patients who are clinically stable
      after recovery from an acute coronary event and who experience angina during
      exercise testing are more aware of physical symptoms in general than are
      comparable patients with silent ischemia. Psychological biases toward or against
      reporting perceived symptoms do not differentiate these groups. Thus, it appears
      that silent ischemia is probably "silent" in the sense of being truly
      asymptomatic rather than of stoic endurance or denial of perceived symptoms.

PMID- 8540444
TI  - Results of direct percutaneous transluminal coronary angioplasty in
      octogenarians.
AB  - Direct percutaneous transluminal coronary angioplasty (PTCA) has emerged as
      effective reperfusion therapy for acute myocardial infarction; however, few data
      exist on its use in octogenarians. Thrombolytic therapy in this age group has
      reduced early mortality from approximately 30% to 20%, but is associated with an
      increased risk of stroke and major hemorrhage. We analyzed the acute and long
      term results of direct PTCA performed on patients aged > or = 80 years at our
      institution between 1980 and 1993. The study group consisted of 55 patients (mean
      patient age 83.3 +/- 2.3 years). Infarcts were anterior in 27 patients (49%).
      Cardiogenic shock was present in 6 patients (11%). The mean time to reperfusion
      was 4.3 +/- 2.8 hours. Direct PTCA was successful in 53 patients (96%). There
      were no emergent bypass operations. In-hospital death occurred in 9 patients
      (16%), including 4 of 6 (67%) presenting in cardiogenic shock and 5 of 49 (10%)
      who were hemodynamically stable on presentation. Repeat PTCA for recurrent
      ischemia was performed in 6 patients (11%). There were no strokes during
      hospitalization. Bleeding complications requiring blood transfusion were present
      in 4 patients (7%). Thirty-day mortality was 16% and 1-year actuarial survival
      was 67%. Direct PTCA in patients aged > or = 80 years can be performed safely
      with a high procedural success rate. The clinical outcome with PTCA in this high
      risk subset of patients compares favorably with that reported previously for both
      thrombolytic and medical therapy.

PMID- 8540445
TI  - Atrial natriuretic peptide and nitric oxide in children with pulmonary
      hypertension after surgical repair of congenital heart disease.
AB  - ANP causes pulmonary vasodilation in some children with pulmonary hypertension
      secondary to congenital heart disease. In a small group of patients, ANP lowered
      mean pulmonary artery pressure and pulmonary vascular resistance index > 20%
      without changing systemic vascular resistance index. Inhaled NO is an effective
      pulmonary vasodilator and is a more selective pulmonary vasodilator than ANP. The
      utility of ANP may be limited by its nonselective effects as more selective
      vasodilator agents are available.

PMID- 8540446
TI  - Usefulness of transesophageal echocardiography for positioning the intraaortic
      balloon pump in the operating room.

PMID- 8540447
TI  - Frequency of primary tumors of the heart.
AB  - Primary tumors of the heart are rare. Based upon the data of 22 large autopsy
      series, the frequency of primary cardiac tumors is approximately 0.02%-
      corresponding to 200 tumors in 1 million autopsies (Table I).

PMID- 8540448
TI  - Ultrasound imaging of the radial artery following its use for cardiac
      catheterization.
AB  - Our experience suggests transradial arterial access with 5Fr catheters can be
      used for cardiac angiography with a low incidence of clinical complications, and
      supports the findings of previous investigators. Subclinical complications at the
      catheterization site were infrequent in this study (1 patient with asymptomatic
      radial artery occlusion). The presence of a palpable radial pulse may not be a
      reliable estimate of artery patency as evidenced by our patient with a palpable
      pulse due to retrograde flow. The theoretical advantage of the procedure is
      derived from the dual vascular supply to the hand. Radial artery occlusion, while
      uncommon, results in no ischemic sequelae in the setting of a patent ulnar
      artery.

PMID- 8540449
TI  - Danger of amiodarone therapy and elevated inspired oxygen concentrations in mice.
AB  - Our study showed a statistically significant incidence of pulmonary edema in mice
      receiving amiodarone and 100% oxygen. This finding, together with a variety of
      clinical reports, indicates that in patients receiving amiodarone therapy, FiO2
      should be maintained at the lowest possible level, consistent with adequate
      oxygenation.

PMID- 8540450
TI  - Percutaneous cardiopulmonary bypass-supported coronary angioplasty in patients
      with unstable angina pectoris or myocardial infarction and a left ventricular
      ejection fraction < or = 25%.
AB  - The objective of this study was to determine the acute and long-term results of
      percutaneous cardiopulmonary bypass-supported angioplasty in treating high-risk
      patients with unstable presentations and severely depressed left ventricular (LV)
      function (ejection fraction [EF] < or = 25%). One hundred seven consecutive
      patients with a mean LVEF of 19 +/- 3% were studied. Seventy-four patients (69%)
      had unstable angina, 60 (56%) had New York Heart Association class III or IV
      symptoms, 74 (69%) had recent (< 15 days) documented acute myocardial infarction,
      103 (96%) had 3-vessel disease, and 58 (54%) had only 1 remaining patent artery.
      A total of 50 patients (47%) were deemed unsuitable for bypass surgery. Of 196
      severe narrowings attempted in 166 coronary arteries, 193 (98%) were successfully
      dilated in 105 patients (98%), and there was no procedure-related mortality, Q
      wave myocardial infarction, or urgent requirement for coronary bypass surgery.
      There were 5 in-hospital deaths (4.7%) and the remaining 102 patients have been
      followed for 24.5 +/- 1.3 (mean +/- SE) months. Twenty-three patients (21%) died
      between 1 and 23 months after the procedure. One- and 2-year survival free of
      cardiac death was 83% and 77%, respectively. Of the 79 surviving patients, 65
      have survived event free of myocardial infarction and revascularization; event
      free survival for 1 and 2 years was 76% and 69.5%, respectively. In the 64
      patients in whom LV function was measured before and after the procedure, global
      EF increased from 20.6% to 29.3% (p < 0.001). Patients who remained event free
      had a greater improvement in LVEF than those who had a cardiac event during
      follow-up (p < 0.05). Thus, this study demonstrates the safety and efficacy of
      percutaneous cardiopulmonary bypass-supported angioplasty in the immediate
      treatment of high-risk unstable patients with multivessel coronary artery disease
      and severely depressed LV function.

PMID- 8540451
TI  - Effect of beta blockade on heart rate variability during vessel occlusion at the
      time of coronary angioplasty.
AB  - Beta blockers modify cardiovascular neural regulation, which may contribute to
      their protective effect against sudden cardiac death. To evaluate the effects of
      beta blockade on cardiovascular autonomic reactions caused by acute coronary
      occlusion in humans, heart rate (HR) variability was analyzed in the time and
      frequency domains immediately before and during balloon occlusion of a coronary
      artery in 116 patients randomly assigned to either chronic beta-blocker therapy
      (beta-blocker group) or no beta blockade (control group) during elective 1-vessel
      coronary angioplasty. Coronary occlusion (mean 112 seconds) caused a significant
      increase in both the high- and low-frequency components of HR variability in the
      control group (n = 58), from 2.7 +/- 1.6 to 3.4 +/- 1.7 (logarithmic units, p <
      0.001) and from 4.3 +/- 1.3 to 4.8 +/- 1.5 (p < 0.01), respectively, whereas in
      the beta-blocker group (n = 58), the high-frequency power did not change during
      occlusion, but the low-frequency power increased from 3.9 +/- 1.4 to 4.4 +/- 1.4
      (p = 0.01). Changes in high- and low-frequency components and HR were related to
      the change in systolic blood pressure during occlusion in the beta-blocker group
      (r = 0.53, p < 0.001; r = 0.34, p < 0.05; and r = -0.41, p < 0.01, respectively),
      but not in the control group (r = -0.17, r = -0.14, and r = 0.24, respectively).
      Thus, beta blockade attenuates the initial vagal activation associated with acute
      coronary occlusion and seems to maintain baroreflex-mediated cardiovascular
      control. The maintained integrity of baroreflex regulation and the alleviation of
      extreme autonomic reactions during beta blockade may modify the clinical outcome
      of acute coronary occlusion in a beneficial way.

PMID- 8540452
TI  - Postischemic functional recovery and BMIPP uptake after primary percutaneous
      transluminal coronary angioplasty in acute myocardial infarction.
AB  - To correlate asynergic wall motion after primary percutaneous transluminal
      coronary angioplasty with myocardial perfusion and fatty acid metabolism,
      quantitative tomographies using thallium and radioiodinated 15-(p-iodophenyl)-3
      R,S-methylpentadecanoic acid (BMIPP) were performed during the acute and recovery
      stages in 56 consecutive patients with acute myocardial infarction, of whom 32
      underwent primary percutaneous transluminal coronary angioplasty (group A) and 24
      were conservatively treated (group B); 44 patients (79%) had 1-vessel disease.
      Reduced myocardial uptakes of thallium and BMIPP and regional wall motion were
      quantified with a bull's eye technique and a centerline method using contrast
      left ventriculography, respectively. BMIPP activity was significantly lower than
      that of thallium at an acute stage in both groups. Abnormal BMIPP activities and
      the difference in thallium and BMIPP abnormalities (perfusion metabolism
      mismatch) at an acute stage decreased significantly during follow-up in group A
      (111 +/- 13 to 99 +/- 12 and 30 +/- 10 to 15 +/- 10, respectively), and not in
      group B (129 +/- 31 vs 118 +/- 29 and 29 +/- 13 vs 30 +/- 10, respectively).
      Improvement in regional wall motion abnormality correlated closely with the
      improved uptakes of thallium and BMIPP (y = 0.64x + 26.4, r = 0.56, p < 0.05; y =
      1.1x + 11.1, r = 0.81, p < 0.001; respectively). The mismatched uptake of both
      tracers at an acute stage was significantly related to recovery from asynergic
      wall motion during follow-up in group A (y = 0.45x + 13.9, r = 0.65, p < 0.005).
      In conclusion, despite restored myocardial perfusion by primary coronary
      angioplasty, BMIPP uptake is impaired in salvaged myocardium at an acute stage of
      infarction. However, the degree and improvement of perfusion metabolism mismatch
      in acute myocardial infarction may reflect subsequent recovery from postischemic
      wall motion abnormality in metabolically impaired but viable myocardium after
      coronary reperfusion.

PMID- 8540453
TI  - Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass
      graft patency.
AB  - Epidemiologic and experimental data suggest that a high dietary intake of long
      chain polyunsaturated n-3 fatty acids may reduce the risk of atherothrombotic
      disease. In a randomized, controlled study, 610 patients undergoing coronary
      artery bypass grafting were assigned either to a fish oil group, receiving 4
      g/day of fish oil concentrate, or to a control group. All patients received
      antithrombotic treatment, either aspirin or warfarin. Their diet and serum
      phospholipid fatty acid profiles were monitored. The primary end point was 1-year
      graft patency, which was assessed by angiography in 95% of patients. Vein graft
      occlusion rates per distal anastomoses were 27% in the fish oil group and 33% in
      the control group (odds ratio 0.77, 95% confidence interval, 0.60 to 0.99, p =
      0.034). In the fish oil group, 43% of the patients had > or = 1 occluded vein
      graft(s) compared with 51% in the control group (odds ratio 0.72, 95% confidence
      interval, 0.51 to 1.01, p = 0.05). Moreover, in the entire patient group, there
      was a significant trend to fewer patients with vein graft occlusions with
      increasing relative change in serum phospholipid n-3 fatty acids during the study
      period (p for linear trend = 0.0037). Thus, in patients undergoing coronary
      artery bypass grafting, dietary supplementation with n-3 fatty acids reduced the
      incidence of vein graft occlusion, and an inverse relation between relative
      change in serum phospholipid n-3 fatty acids and vein graft occlusions was
      observed.

PMID- 8540454
TI  - Changes in flow-mediated brachial artery vasoactivity with lowering of desirable
      cholesterol levels in healthy middle-aged men.
AB  - Current National Cholesterol Education Program guidelines consider desirable
      total and low-density lipoprotein cholesterol levels to be < 200 and < 160 mg/dl,
      respectively, for healthy individuals without multiple coronary risk factors. To
      determine the extent to which these levels affect vascular function, we assessed
      flow-mediated (endothelium-dependent) brachial artery vasoactivity noninvasively
      before, during, and after cholesterol lowering (simvastatin 10 mg/day) in 7
      healthy middle-aged men with cholesterol levels meeting current recommendations.
      Flow-mediated brachial artery vasoactivity was measured using 7.5 MHz ultrasound
      and expressed as percent diameter change from baseline to hyperemic conditions (1
      minute following 5 minutes of blood pressure cuff arterial occlusion). Flow
      mediated vasoactivity rose from 5.0 +/- 3.6% at baseline to 10.5 +/- 5.6%, 13.3
      +/- 4.3%, and 15.7 +/- 4.9% (all p < 0.05) as cholesterol fell from 200 +/- 12 to
      161 +/- 18, 169 +/- 16, and 153 +/- 11 mg/dl after 2, 4, and 12 weeks,
      respectively, of cholesterol-lowering therapy. Vasoactivity and cholesterol
      returned to baseline levels 12 weeks after simvastatin discontinuation. Overall,
      vasoactivity was found to correlate inversely with cholesterol levels (r = -0.47,
      p = 0.004). These data suggest that flow-mediated brachial artery vasoactivity
      responds rapidly to changes in cholesterol levels and that endothelial function
      improves by lowering cholesterol levels below recommendations of current
      guidelines.

PMID- 8540455
TI  - Complications of diagnostic electrophysiologic studies and radiofrequency
      catheter ablation in patients with tachyarrhythmias: an eight-year survey of
      3,966 consecutive procedures in a tertiary referral center.
AB  - Predictors and comparisons of complications in patients with electrophysiologic
      study or radiofrequency ablation have not been assessed in previous published
      reports. The purpose of this study was to prospectively evaluate the procedure
      specific complications and investigate the possible causes and predictors of
      complications in electrophysiologic study and radiofrequency ablation. Data of
      diagnostic electrophysiologic studies and radiofrequency ablation were
      prospective, and represented a consecutive series of 2,593 patients with 3,966
      procedures. The present study showed that a significantly higher complication
      rate occurred in radiofrequency ablation than in electrophysiologic study (3.1%
      vs. 1.1%, respectively, p = 0.00002) and a significantly higher complication rate
      occurred in elderly than in young patients with electrophysiologic study (2.2% vs
      0.5%, p = 0.0002) or radiofrequency ablation (6.1% vs 2.0%, p = 0.00015).
      Multiple logistic analysis found that older age (p < 0.01) and systemic disease
      in elderly patients (p < 0.01) were the independent predictors of complications
      in both procedures. Furthermore, there was no temporal trend in the incidence of
      complication. We conclude that the incidence of complication was higher in
      radiofrequency ablation, and elderly patients had a higher incidence of
      complications in both electrophysiologic study and radiofrequency ablation; these
      procedures, when performed by experienced personnel in an appropriately staffed
      and equipped laboratory, can be undertaken with an acceptable risk.

PMID- 8540456
TI  - Natural history, determinants, and clinical relevance of conduction abnormalities
      following orthotopic heart transplantation.
AB  - To study the long-term evolution, determinants, and clinical relevance of the
      conduction abnormalities after orthotopic heart transplantation, 87 patients,
      followed for a mean of 105 +/- 72 weeks, were divided into 3 groups according to
      the characteristics of their electrocardiograms compared with their initial
      electrocardiogram recorded at study entry. The first group consisted of 24
      patients whose initial electrocardiogram was normal, and subsequent
      electrocardiograms remained normal throughout the study. The second group
      included 27 patients who developed electrocardiographic evidence of progressive
      conduction system damage. The third group comprised 36 patients whose initial
      electrocardiogram was abnormal and subsequent electrocardiograms remained
      unchanged during follow-up. Although the hemodynamic and echocardiographic
      evaluation of right and left ventricular function were initially similar among
      the 3 groups, groups 2 and 3 demonstrated a significant deterioration of left
      ventricular ejection fraction (62 +/- 12% to 55 +/- 16% and 62 +/- 8% to 57 +/-
      14%, respectively; p < 0.05) and cardiac index (2.7 +/- 0.6 to 2.3 +/- 0.5 and
      3.0 +/- 0.9 to 2.5 +/- 0.9 L/min/m2, respectively; p < 0.05) while patients in
      group 1 maintained their normal baseline indices. Incidence and progression of
      coronary artery disease, as well as frequency of rejection episodes, were
      comparable among the groups. Mortality was higher in the 2 groups with evidence
      of conduction defects. Sudden death associated with complete heart block (2
      patients) or ventricular arrhythmias (3 patients) was exclusively confined to
      patients with evidence of progressive electrocardiogram abnormalities. We
      conclude that, following orthotopic heart transplantation, stable or progressive
      conduction system damage on the electrocardiogram is associated with left
      ventricular dysfunction and increased mortality. Sudden death is not uncommon
      among patients demonstrating worsening cardiac conduction and, in some cases, is
      related to the development of potentially preventable complete heart block.

PMID- 8540457
TI  - Sympathetic reinnervation after acute myocardial infarction.
AB  - Myocardial infarction produces sympathetic denervation of the necrotic myocardium
      and noninfarcted myocardium apical to the injury. Proof of sympathetic
      reinnervation after myocardial infarction has, however, remained elusive. In this
      study, we investigated whether cardiac sympathetic reinnervation occurs in men
      recovering from myocardial infarction. I-123 metaiodobenzylguanidine (MIBG), I
      123 paraphenylpentadecanoic acid, and Tc-99m sestamibi scintigraphic imaging were
      conducted in 13 men 3 and 12 months after a first myocardial infarction to
      determine the extent of denervated myocardium, the size of the infarct, and the
      size of the myocardium with reduced perfusion, respectively. A defect was
      determined as regional uptake of < or = 30% of the maximal myocardial activity.
      The size of the MIBG defect was not significantly different between 3 and 12
      months after infarction (17 +/- 8% and 18 +/- 8% of left ventricular mass,
      respectively). There was also no significant change in the extent of viable but
      denervated myocardium at 3 and 12 months (average 9 +/- 6% and 10 +/- 5%,
      respectively). MIBG activity of the infarct zone (expressed as a percentage of
      MIBG activity of the myocardium with normal perfusion) did not change (17 +/- 13%
      and 20 +/- 16%), whereas MIBG activity of the periinfarct zone increased during
      follow-up (32 +/- 11% and 41 +/- 14%, p < 0.01). This was associated with an
      increase in periinfarct I-123 paraphenylpentadecanoic acid activity (40 +/- 11%
      and 48 +/- 9%, p < 0.05), but not Tc-99m sestamibi activity (48 +/- 10% and 48 +/
      11%). In conclusion, we did not observe sympathetic reinnervation in the infarct
      zone between 3 and 12 months after myocardial infarction. However, MIBG activity
      of the periinfarct zone increased, suggesting partial reinnervation, and this was
      associated with a recovery of myocardial metabolic activity of the periinfarct
      zone.

PMID- 8540458
TI  - Electrophysiologic characteristics and radiofrequency catheter ablation in
      patients with multiple atrioventricular nodal reentry tachycardias.
AB  - Information about the mechanism and radiofrequency catheter ablation of multiple
      atrioventricular (AV) nodal reentry tachycardias is limited. Among the 550
      consecutive patients with AV nodal reentry tachycardia, 36 with multiple forms of
      AV nodal reentry tachycardia were included in this study. Electrophysiologic
      characteristics, as well as the efficacy and safety of radiofrequency ablation,
      were evaluated. Results showed that anterograde dual pathways were seen in 32
      patients and triple pathways in 2, and retrograde dual pathways were seen in 23
      patients and triple pathways in 11. Twenty-two patients had 2 types, 7 had 3
      types, 5 had 4 types, and 2 had 5 types of AV nodal reentry tachycardia and
      echoes. After delivering radiofrequency energy to the target sites, 32 patients
      had no induction of AV nodal reentry tachycardia and only 4 had induction of 1
      echo. Furthermore, 22 patients (61%) had simultaneous elimination or modification
      of the slow and/or intermediate pathways in the anterograde and retrograde
      direction. During the follow-up period of 19 +/- 14 months, 2 patients had
      recurrence of tachycardia. Thus, multiple anterograde and retrograde AV nodal
      pathways were present in the human AV node and they constituted the substrates of
      reentry circuits. Radiofrequency catheter ablation was safe and effective in
      eliminating the slow and intermediate pathways for maintenance of multiple AV
      nodal reentry tachycardias.

PMID- 8540459
TI  - Body surface distribution of significant changes in QRST time-integral values
      after radiofrequency catheter ablation in patients with Wolff-Parkinson-White
      syndrome.
AB  - We analyzed 87-lead body surface QRST time-integral values (QRST values) in 29
      patients with Wolff-Parkinson-White syndrome (group A, 17 patients with manifest
      left-sided accessory pathway; group B, 6 patients with manifest right-sided
      accessory pathway; and group C, 6 patients with concealed left-sided accessory
      pathway), before, 1 day after, and 1 week after radiofrequency catheter ablation
      (RCA). The number of leads with abnormal QRST values was significantly lower 1
      week after RCA compared with those before RCA and 1 day after RCA in groups A and
      B (p < 0.05); there was no significant difference in QRST values before and 1 day
      after RCA in groups A and B. The QRST values over areas with preexisting
      repolarization abnormalities were significantly altered 1 week after RCA compared
      with before and 1 day after RCA in groups A and B (p < 0.01). However, there was
      no significant difference in the QRST values over areas without preexisting
      abnormalities before RCA. In group C, there were no significant differences in
      the QRST values or the number of leads with abnormal QRST values before, 1 day
      and 1 week after RCA. In conclusion, RCA did not significantly influence
      repolarization properties over areas without preexisting abnormalities, but
      gradually reduced preexisting repolarization abnormalities, which were closely
      related to the location of the accessory pathway in patients with manifest Wolff
      Parkinson-White syndrome. Our results suggest that body surface QRST values are
      useful for assessment of repolarization abnormalities during the periablation
      period.

PMID- 8540460
TI  - Transesophageal echo phase imaging for localizing accessory pathways during
      adenosine-induced preexcitation in patients with the Wolff-Parkinson-White
      syndrome.
AB  - Transesophageal phase images and precordial electrocardiography (ECG) were used
      to localize accessory pathways during adenosine-induced preexcitation in 30
      patients (18 men, mean age +/- SD 33 +/- 14 years) undergoing endocardial mapping
      for suspected Wolff-Parkinson-White syndrome. Digitized 2-dimensional
      echocardiographic cine loops were mathematically transformed using a first
      harmonic Fourier algorithm before and after catheter ablation. Endocardial
      mapping found single accessory pathways with anterograde conduction in 20
      patients, concealed pathways in 7, and atrioventricular reentry circuits in 3
      patients. At baseline, precordial ECG correctly localized 8 pathways (40%) with
      anterograde conduction and predicted 5 adjacent locations (25%), but findings
      were normal in 7 patients (35%). Phase imaging correctly identified only 3
      pathway locations (15%), findings were normal in 15 (75%), and could not be
      obtained in 2 patients (10%). Adenosine augmented manifest but minimal
      preexcitation in 9 patients and unmasked latent preexcitation in 7. In 4
      patients, preexcitation was already maximal at baseline. During adenosine
      augmented preexcitation, ECG correctly identified 13 locations (65%), but still
      predicted 7 adjacent locations (35%). However, phase imaging correctly identified
      15 locations (75%) and predicted only 3 adjacent locations (15%). All midseptal
      (n = 2) and anteroseptal (n = 2) locations were correctly identified by phase
      imaging, but none by ECG. On follow-up studies in 16 patients, successful
      catheter ablation (n = 13) was equally well confirmed by ECG and phase imaging.
      Therefore, transesophageal echocardiographic phase imaging during adenosine
      induced preexcitation is a readily available and safe procedure that appears
      clinically most useful for identifying septal pathways.

PMID- 8540461
TI  - Early assessment by transesophageal echocardiography of left atrial appendage
      function after percutaneous mitral commissurotomy.
AB  - Thirty-seven consecutively admitted patients with severe mitral stenosis
      underwent percutaneous mitral commissurotomy with a transthoracic and biplane or
      multiplane transesophageal echocardiographic examination before and between 24
      and 48 hours after percutaneous mitral commissurotomy. Thirty patients (81%) were
      in sinus rhythm and 7 were in atrial fibrillation. Left atrial appendage (LAA)
      function was evaluated in both the transverse and the longitudinal planes by
      planimetry and pulsed Doppler echocardiographic interrogation at the LAA outlet.
      Percutaneous mitral commissurotomy resulted in a twofold increase in mitral valve
      area, and no severe mitral regurgitation occurred. With use of the planimetry
      method, there was no significant improvement in LAA ejection fraction, except in
      the transverse plane for patients in sinus rhythm (p = 0.03). With use of Doppler
      method, 3 distinct flow patterns were observed before the procedure: a "sinus
      pattern" in patients in sinus rhythm, and a "fibrillatory pattern" (n = 3) or a
      "no-flow pattern" (n = 4) in patients in atrial fibrillation. After
      commissurotomy, there was a marked increase in LAA peak Doppler velocity (+62%)
      and in LAA velocity time integral (+31%). Of the 4 patients in atrial
      fibrillation with a no-flow pattern, 2 had recovery of a typical effective
      fibrillatory flow pattern after the procedure. The increase in peak Doppler
      velocity after commissurotomy was related to the decrease or regression in left
      atrial spontaneous echo contrast, and correlated with the increase in mitral
      valve area, the decrease in tranmitral pressure gradient, and the increase in
      cardiac index; improvement in valve function after successful percutaneous mitral
      commissurotomy is associated with early improvement in LAA function.

PMID- 8540462
TI  - Frequency and significance of left ventricular thickening in transplanted hearts
      in children.
AB  - The pediatric myocardium has been shown to thicken markedly during steroid
      administration for the treatment of pulmonary or neurologic disease. Yet, in the
      pediatric heart transplant patient, left ventricular (LV) thickening is sometimes
      used as a marker for rejection without accounting for steroid immunosuppression.
      The aim of this study was to determine timing and correlates of changes in LV
      thickness in pediatric cardiac transplant patients. In 11 patients (11 days old
      to 16 years old), LV thickness (mass) was first measured during the entire post
      transplant course. Second, thickness was measured before and during rejection.
      Last, to separate the independent effects of rejection and steroids on LV mass,
      echocardiograms were reviewed in the immediate post-transplant period, when our
      protocol prescribes dramatic changes in steroid doses and rejection episodes were
      rare. Specifically, the donor heart underwent 5 evaluations: at donation, at peak
      steroid dose, 5 days after peak steroid dose, at moderate steroid dose, and at
      very low maintenance dose. LV mass changed most dramatically and consistently
      during the first 20 to 40 days after transplant. Thereafter, mass had little
      consistent changes and did not change significantly during any of the 52
      rejection episodes. Mass increased 5 days after peak steroid dose (54 +/- 30 to
      74 +/- 38 g/ht2.7, p < 0.05) and decreased during low maintenance levels of
      steroids. Thickening was associated with cumulative steroid dose (r = 0.66, p =
      0.03) and age (r = -0.62, p = 0.04). Thus, in pediatric heart transplant
      patients, as in other pediatric diseases, LV thickening is associated with
      steroid administration. Thickening may be an unreliable marker for acute cellular
      rejection.

PMID- 8540463
TI  - Do calcium antagonists cause myocardial infarction?

PMID- 8540464
TI  - The efficacy and safety of pravastatin in patients aged 60 to 85 years with low
      density lipoprotein cholesterol > 160 mg/dl.
AB  - This study demonstrated that pravastatin 20 mg once daily significantly lowered
      total cholesterol (by 19%) and LDL cholesterol by 25%.

PMID- 8540466
TI  - Fate of the resting perfusion defect as assessed with technetium-99m methoxy
      isobutyl-isonitrile single-photon emission computed tomography after successful
      revascularization in patients with healed myocardial infarction.
AB  - It is concluded that in patients with healed myocardial infarction, MIBI uptake
      at rest underestimates myocardial viability and may improve significantly if
      blood flow is restored. Patients with MIBI defects at rest may therefore take
      advantage of revascularization.

PMID- 8540467
TI  - Imaging of coronary artery microstructure (in vitro) with optical coherence
      tomography.
AB  - OCT achieves high-resolution and image differentiation of vascular tissues to a
      degree that has not been previously possible with any method except excisional
      biopsy. Thus, OCT represents a promising new diagnostic technology for
      intracoronary imaging, which could permit the in vivo evaluation of critical
      vascular pathology.

PMID- 8540465
TI  - Episodic activation of the coagulation system in unstable angina does not elicit
      an acute phase reaction.
AB  - The results of our study suggest that the acute phase response may be partly
      related to a yet unknown primary inflammatory component in unstable angina.
      Further studies are needed to elucidate the actual role of inflammation in
      unstable angina and its relation to activation of the coagulation system.

PMID- 8540468
TI  - Reduction in left ventricular mass in patients with systemic hypertension treated
      with enalapril, lisinopril, or fosenopril.
AB  - There are still conflicting data as to whether reduction in LV mass is
      beneficial. In the present study, no deterioration in LV systolic function
      occurred in patients in whom regression of LV mass was achieved. Impairment in LV
      compliance has been shown in hypertensive patients, even in the presence of
      preserved systolic function and normal LV mass. In our study, improvement in
      diastolic function was observed only in patients whose LV mass decreased, and it
      was related to reduction in mass and not to a decrease in mean arterial pressure.
      Therefore, we suggest that because diastolic function is the first activity to
      deteriorate in hypertensive patients, it may be the first activity to improve,
      and this improvement may be related to reduction in LV mass with ACE inhibitors.

PMID- 8540469
TI  - Prevalence and predictors of atrial fibrillation in rheumatic valvular heart
      disease.
AB  - The highest frequency of AF in RHD occurs in those with mitral stenosis, mitral
      regurgitation, and tricuspid regurgitation in combination. AF, while occurring in
      29% of patients with isolated mitral stenosis and in 16% with isolated mitral
      regurgitation, is an infrequent finding (1%) in patients with aortic valvular
      disease. Left atrial diameter by univariate analysis, and age and left atrial
      diameter by multivariate analysis have been shown to be the most important
      parameters to determine the occurrence of AF in patients with RHD.

PMID- 8540470
TI  - Effects of mitral and/or aortic valve replacement or repair on endothelium
      dependent peripheral vasorelaxation and its relation to improvement in exercise
      capacity.

PMID- 8540471
TI  - Treatment of a Class II, Division 1 malocclusion with the Jasper Jumper: a case
      report.

PMID- 8540472
TI  - Windows 95: should you upgrade now or wait.

PMID- 8540473
TI  - Comment on correction of a severe Class II malocclusion case report.

PMID- 8540474
TI  - The wrong paradigm.

PMID- 8540475
TI  - Comment on soft tissue profile by Dr. Polk.

PMID- 8540476
TI  - Fracture strength of ceramic brackets during arch wire torsion.
AB  - This study evaluated the fracture strengths of eight new vintage ceramic brackets
      with application of torsional forces. Palatal root torque was applied at the
      distal side of right maxillary central incisor brackets with 0.022-inch slots by
      means of a 0.0215 x 0.027-inch rounded edge stainless steel arch wire. A
      specially designed apparatus that attached to an Instron machine was used to test
      the ceramic brackets. The amount of torque, degrees of torsion at failure, and
      fracture locations were measured. The monocrystalline bracket did not break when
      the torquing test was applied; the portion of the wire outside the slot of the
      bracket twisted on itself. The mean torquing forces at failure ranged from 5755.2
      gm-mm to 9316.5 gm-mm and could be separated into three statistically different
      groups. The mean torsional rotation at fracture ranged from 32.7 degrees to 68.1
      degrees for the polycrystalline brackets. The results suggested that all the
      brackets studied were sufficiently strong to withstand the commonly accepted
      magnitudes of arch wire torquing forces. The present investigation showed higher
      angulation values for all the brackets than those reported by Holt who used the
      same apparatus with older style brackets.

PMID- 8540477
TI  - Comment on cost, risk, regulation, fees.

PMID- 8540478
TI  - Comment on health care.

PMID- 8540479
TI  - Comment on extrusion of the ectopic maxillary canine.

PMID- 8540480
TI  - Prevalence and severity of apical root resorption and alveolar bone loss in
      orthodontically treated adults.
AB  - This study assessed the frequency of root resorption and alveolar bone loss in 88
      adults who had undergone orthodontic treatment. Pretreatment and posttreatment
      periapical radiographs were used to determine the amount of external apical root
      resorption and alveolar bone loss of the maxillary and mandibular incisors.
      Alveolar bone loss in the posterior quadrants was determined from bite-wing
      radiographs. The number of incisors showing root resorption, including blunting,
      increased from 15% before treatment to 73% after treatment. The number of
      incisors having moderate to severe apical root resorption was 2% before treatment
      and 24.5% after treatment. The number of anterior sites in which loss of alveolar
      bone height exceeded 2 mm from the cementoenamel junction to the alveolar crest
      increased from 19% before treatment to 37% after treatment; the number of
      posterior sites was 7% before treatment and 14% after treatment. Bone LOSS > or =
      1.5 mm from the pretreatment to posttreatment stages occurred in 11% of the
      incisors and 3% of the posterior sites. A marked increase in the prevalence of
      root resorption and alveolar bone loss occurred over the course of treatment. The
      prevalence of iatrogenic effects for adults may be higher for incisors than in
      previously reported adolescent studies. A small subgroup with multiple sites of
      either root resorption or bone loss account for a disproportionate number of
      iatrogenic sequelae. However, in general, the iatrogenic experience did not
      preclude the orthodontic treatment of adults.

PMID- 8540481
TI  - Soft tissue and dentoskeletal profile changes associated with maxillary expansion
      and protraction headgear treatment.
AB  - One of the goals of early treatment of Class III malocclusion with maxillary
      expansion and protraction headgear is to significantly improve the dentofacial
      profile. The objectives of the present study were to determine (1) the
      interrelationships of the soft tissue and dentoskeletal profiles after maxillary
      expansion and protraction headgear treatment and (2) which cephalometric
      variables could contribute to an accurate prediction of the protraction effect on
      the soft tissue profile. Lateral cephalometric radiographs of 20 consecutively
      treated Class III patients (10 males, 10 females) by protraction headgear were
      included in this study. Their ages at the start of protraction headgear treatment
      ranged from 6 to 11 years, with an average of 8.1 +/- 2.1 years. None of the
      patients had previous orthodontic treatment. For each patient, the first lateral
      cephalogram was taken 6 months before the initiation of headgear treatment (T0),
      and the second radiograph at the start of treatment (T1). Therefore (T1-T0)
      represented 6 months of growth with no treatment. A third radiograph was taken 6
      months after start of treatment (T2). In this way, (T2-T1)-(T1-T0) represented
      the effect the result of appliance therapy alone and each subject served as
      his/her own control. A computerized cephalometric analysis was used including
      variables assessing sagittal and vertical relationships of skeletal and soft
      tissue profiles, incisal relationships, soft tissue thickness, and lip structure.
      Data were analyzed by means of paired t tests, Pearson's product-moment
      coefficient correlation, and multiple regression analyses. The results showed
      significant improvements in dentofacial profile after 6 months of maxillary
      protraction. The skeletal and soft tissue facial profiles were straightened and
      the posture of the lips was improved. The normal incisal relationship (overjet)
      that was achieved had a significant impact on the soft tissues overlying both
      upper and lower incisors resulting in better lip competence and posture.
      Significant correlations were found between changes in the sagittal relationships
      of skeletal and soft tissue profiles in both the maxilla and the mandible (p <
      0.05). The forward movement of the maxilla was accompanied by a corresponding
      forward movement of the soft tissue profile at 50% to 79% of the hard tissue. In
      the mandible, the downward and backward movements of the soft tissues were
      equivalent to 71% to 81% of the corresponding hard tissues. The lack of high r
      square values in the multiple regression analyses reflected a low prediction
      value for the maxillary variables, but moderately high prediction value for the
      mandibular variables that could be used in preorthopedic treatment planning. This
      study showed that significant dentoskeletal changes and improvements in
      dentofacial profile resulted from 6 months of treatment with maxillary expansion
      and protraction.

PMID- 8540482
TI  - A study of force application, amount of retarding force, and bracket width in
      sliding mechanics.
AB  - We investigated the relationship of the retraction force to the location of force
      application, retarding force and bracket width during simulated sliding tooth
      movement along an arch wire. Point 1 for retraction was located at the center of
      the bracket, and points 2 and 3 were at 4.0 mm and 6.0 mm from the bracket slot,
      respectively. Weights of 100 gm, 200 gm, and 400 gm were suspended at 9.0 mm from
      the bracket slot as the point of simulated center of resistance. Stainless steel
      standard edgewise wide, medium, and narrow twin brackets were engaged with two
      elastomeric ligatures on a stainless steel wire (0.016 x 0.016 inch). The bracket
      was retracted at the rate of 0.1 mm per second for a distance of 2.0 mm.
      Measurements were repeated six times, and the results were compared with multiple
      ANOVA tests. For all brackets, with an increase of the retarding weight, the mean
      retraction force at points 1 and 2 increased but decreased at point 3. The mean
      retraction force at point 1 for the narrow twin bracket was significantly (p <
      0.05) higher than that for the wide twin bracket at all retarding force levels.
      However, the mean retraction force at points 2 and 3 for the narrow twin bracket
      was significantly (p < 0.05) lower than for the wide twin bracket at all
      retarding force levels. These findings indicated that the point of force
      application, the resistance force of a tooth, and the width of the bracket are
      crucial in consideration of the tipping moments on the bracket.

PMID- 8540483
TI  - A scanning electron microscopy comparison of enamel polishing methods after air
      rotor stripping.
AB  - In the last few years, orthodontic literature has shown particular interest in
      the interproximal enamel reduction technique described as stripping or
      slenderizing. Most researchers have shown, by scanning electron microscopy (SEM)
      studies, the difficulties encountered while attempting to remove coarse abrasions
      left after stripping with the first instrument. The objective of this SEM study
      was to compare the different polishing methods proposed in the literature and to
      assess the efficiency of our own procedure. For this purpose, 48 healthy human
      teeth (premolars and molars) were used after removal for orthodontic or
      periodontal reasons. The teeth were divided into eight groups of six teeth each
      (two molars and four premolars), and mounted on a typodont to simulate a clinical
      situation. Each group underwent stripping according to one of the following
      techniques: 16-blade tungsten carbide bur and fine and ultrafine diamond burs;
      coarse diamond bur and fine and ultrafine diamond burs; coarse diamond disk and
      Sof-Lex disks (Dental products/3M, St. Paul, Minn.); 16-blade tungsten carbide
      bur and phosphoric acid on finishing strip; and 8-straight blade tungsten carbide
      diamond bur and Sof-Lex disks. The SEM investigations demonstrated that it is not
      possible to eliminate, with normal polishing and cleaning methods, the furrows
      left on the enamel both by the diamond burs and the diamond disks and the 16
      blade tungsten carbide burs. Mechanical and chemical stripping as well did not
      prove to be effective. By contrast, with the use of a 8-straight blade tungsten
      carbide bur followed by Sof-Lex disks for polishing the enamel, it is possible to
      obtain well-polished surfaces that many times appear smoother than the intact or
      untreated enamel.

PMID- 8540484
TI  - Bond strength of rebonded orthodontic brackets.
AB  - A study was undertaken to determine the bond strength of brackets rebonded with a
      no-mix resin system or a paste-paste resin system. The efficacy of plastic
      conditioner and Enhance adhesion booster (Reliance Orthodontic Products, Inc.,
      Itasca, Ill.) as an aid in rebonding was also evaluated. Sixty extracted human
      premolars were divided into two groups based on the two adhesive systems used.
      Both groups of 30 were subdivided and (1) initial bond, (2) rebond, and (3)
      rebond using plastic conditioner and adhesion booster. Samples were stressed to
      bond failure using an Instron machine. Bond separation occurred in the majority
      of samples at the enamel/resin interface. Mean bond strengths ranged from 78.8 kg
      cm-2 for rebonding with a no-mix adhesive and no other conditioners, to 182.7 kg
      cm-2 for initial bonding using a paste-paste adhesive. Rebonding using a paste
      paste adhesive with no other conditioners produced a bond strength statistically
      indistinguishable from initial bonding with either system. Plastic conditioner
      and adhesion booster failed to improve rebond strength. The data suggest that,
      given certain circumstances, rebonding is a viable option when a bracket has been
      debonded.

PMID- 8540485
TI  - The role of interdigitation in sagittal growth of the maxillomandibular complex
      in Macaca fascicularis.
AB  - The role of the interdigitation of posterior teeth in maxillomandibular growth
      and development was studied longitudinally in Macaca fascicularis monkeys.
      Fourteen monkeys were divided into a control group (n = 7) and an experimental
      group (n = 7). At the start of the study, the mean age of the animals was 29
      weeks. At that stage the interdigitation in the experimental group was eliminated
      by grinding the cusps of the molars and canines. The animals were followed until
      143 weeks of age and studied with the aid of tantalum implants and lateral
      radiographs. The findings indicated that elimination of the interdigitation
      resulted in a deviating anteroposterior relationship between the jaws and a
      significant inhibition of the vertical growth of the maxilla in the second half
      of the experimental period, while total face height was not noticeably affected.
      As a result, a more prognathic mandible and a more mesial occlusion developed. It
      can be concluded that the interdigitation plays a role in the regulation of
      vertical and anteroposterior facial growth and constitutes an important factor in
      the jaw relation in Macaca fascicularis monkeys.

PMID- 8540486
TI  - Prediction of coronal size of third molars by factor and multiple regression
      analyses.
AB  - Factor analysis and multiple regression analysis were made to establish a method
      for the prediction of the unerupted third molar size. The samples were dental
      casts of 138 adults (69 women and 69 men) who had all their teeth from the
      central incisor to the third molar, at least in one side of each maxillary and
      mandibular dentition. Mesiodistal and buccolingual tooth crown sizes were
      measured with sliding calipers. Five factors were selected from the factor
      analysis on the tooth crown sizes. Multiple regression analysis with the third
      molar as the dependent variable was carried out. Independent variables were
      selected on the basis of the factors obtained from the factor analysis. Two kinds
      of multiple regression equations were obtained (the first molar was used as an
      independent variable in one equation and the second molar was used in the other).
      The accuracy of the prediction was highest when the lateral incisor, the second
      premolar, and the second molar were used as independent variables in the
      maxillary dentition, and the central incisor, the first premolar, and the second
      molar in the mandibular dentition. The mean of the absolute values of the
      differences between the predicted values and the actual values was 0.5 mm in the
      maxillary third molar, and 0.42 mm in the mandibular third molar.

PMID- 8540487
TI  - Force delivery of Ni-Ti coil springs.
AB  - Sentalloy springs (GAC, Central Islip, N.Y.) of the open and closed type were
      investigated with a special designed device. The closed coil springs were
      subjected to a tensile and the open coil springs to a compression test. After a
      first measurement, the springs were activated for a period of 4 weeks and then
      reinvestigated with the same procedure. It could be shown distinctly that, with
      the different coil springs, the force delivery given by the producer could be
      achieved only within certain limits. To remain in the martensitic plateau,
      changed activation ranges, and for the Sentalloy coil springs white and red of
      the open and closed type, also changed force deliveries had to be taken into
      account. There was a distinct decrease in force delivery between the first and
      second measurement. After considering the loading curves of all the Sentalloy
      coil springs and choosing the right activation range respective to the force
      delivery, it was found that the coil springs deliver a superior clinical behavior
      and open new treatment possibilities.

PMID- 8540488
TI  - Facial three-dimensional morphometry.
AB  - Three-dimensional facial morphometry was investigated in a sample of 40 men and
      40 women, with a new noninvasive computerized method. Subjects ranged in age
      between 19 and 32 years, had sound dentitions, and no craniocervical disorders.
      For each subject, 16 cutaneous facial landmarks were automatically collected by a
      system consisting of two infrared camera coupled device (CCD) cameras, real time
      hardware for the recognition of markers, and software for the three-dimensional
      reconstruction of landmarks' x, y, z coordinates. From these landmarks, 15 linear
      and 10 angular measurements, and four linear distance ratios were computed and
      averaged for sex. For all angular values, both samples showed a narrow
      variability and no significant gender differences were demonstrated. Conversely,
      all the linear measurements were significantly higher in men than in women. The
      highest intersample variability was observed for the measurements of facial
      height (prevalent vertical dimension), and the lowest for the measurements of
      facial depth (prevalent horizontal dimension). The proportions of upper and lower
      face height relative to the anterior face height showed a significant sex
      difference. Mean values were in good agreement with literature data collected
      with traditional methods. The described method allowed the direct and noninvasive
      calculation of three-dimensional linear and angular measurements that would be
      usefully applied in clinics as a supplement to the classic x-ray cephalometric
      analyses.

PMID- 8540489
TI  - Orthodontic challenges.

PMID- 8540490
TI  - My thoughts on using cyclosporine in the treatment of inflammatory bowel disease.

PMID- 8540491
TI  - Peritoneovenous shunting in cirrhosis: its role in the management of refractory
      ascites in the 1990s.

PMID- 8540492
TI  - Breathtaking technology for the detection of Helicobacter pylori.

PMID- 8540493
TI  - Surveillance colonoscopy in ulcerative colitis: is the message loud and clear?

PMID- 8540494
TI  - Cyclosporin use in the precolectomy chronic ulcerative colitis patient: a
      community experience and its relationship to prospective and controlled clinical
      trials. Pacific Northwest Gastroenterology Society.
AB  - OBJECTIVE: To define what effect seminal and controlled clinical trials have on
      practice patterns within a gastroenterological community. To define whether these
      practice patterns reproduce reported treatment methods and whether results
      comparable with those reported in such trials are noted within a community
      practice setting. METHODS: Mailed surveies, with telephone follow-up, were sent
      to all members of the Pacific Northwest Gastroenterology Society. Respondents
      were queried regarding cyclosporin use in the precolectomy chronic ulcerative
      colitis (CUC) patient. Data collected included patient demographics, disease
      duration and extent, pre-treatment use of steroids, method, dosage, and duration
      of cyclosporin therapy, side effects, and short-term and subsequent clinical
      results. RESULTS: Twenty-one percent of 81 respondents had used cyclosporin for
      precolectomy CUC, approximately one-half using constant infusion and one-half
      using parenteral bolus therapy. Side effects attributed to the cyclosporin were
      noted in eight of 30 patients (27%), and acute colectomy was avoided in 17
      patients (57%). Subsequent colectomy was required in an additional nine patients
      (73% total) within a 6-month follow-up period, a significantly higher colectomy
      rate than that reported in prospective trials. CONCLUSIONS: Potential reasons
      precluding cyclosporin use within the gastroenterological community may include
      lack of knowledge about cyclosporin therapy for CUC, lack of opportunity,
      skepticism, fear of medication side effects, survey sampling error, or treatment
      philosophy. Potential reasons for failure to duplicate the results reported in
      controlled trials are more complex but may include inadequate treatment duration
      the learning curve associated with the use of a new medication, or acceptance of
      colectomy as the treatment of choice in patients with acutely or chronically
      debilitating disease.

PMID- 8540495
TI  - Prognosis assessment of cirrhotic patients with refractory ascites treated with a
      peritoneovenous shunt.
AB  - OBJECTIVE: The role of peritoneovenous shunt in the management of refractory
      ascites has not been clearly established. The aim of this study was to determine
      readily accessible predictive survival factors in cirrhotic patients with
      refractory ascites treated with a peritoneovenous shunt. METHODS: We studied a
      cohort of 100 cirrhotic patients with refractory ascites who underwent
      peritoneovenous-shunt placement in a university-based reference hospital.
      RESULTS: The estimated median survival of patients after shunt placement was 11
      months (95% CI, 7-14 months). Multivariate analysis based on the proportional
      hazards model disclosed four independent variables associated with poor survival:
      high Pugh score, nonalcoholic etiology, low ascitic fluid protein concentration,
      and history of spontaneous bacterial peritonitis. CONCLUSIONS: Mortality of
      cirrhotic patients treated with a peritoneovenous shunt can be determined by a
      prognostic index using four easily available variables. Such a prognostic index,
      once prospectively validated, could be used as an adjunct in planning treatment
      of cirrhotic patients with refractory ascites.

PMID- 8540496
TI  - Reproducibility of the 14C urea breath test repeated after 1 week.
AB  - OBJECTIVES: The aim of this study was to determine the numerical and categorical
      reproducibility of the 14C urea breath test in a routine clinical setting.
      BACKGROUND: The 14C urea breath test is used for diagnosis of Helicobacter pylori
      infection and is regarded by some centers as the gold standard. METHODS: In 140
      referrals, duplicate tests were performed 1 wk apart. Eighteen patients were
      excluded because they had taken antibiotics or had changed medication that could
      influence the gastric urease activity between the tests. RESULTS: The limits of
      agreement between the repeated tests were 45-234%. Hence, the numerical result of
      a repeated test was 95% likely to differ from the first with a factor of
      approximately two or less. However, when patients were classified as "positive"
      or "negative" according to our previously determined cut-off limit, only three
      patients were discordantly classified by the two tests. The observed agreement
      between the tests was 98%, and the chance-corrected proportional agreement
      (kappa) was 95%, which is far better than that reported for the histological
      diagnosis of gastric H. pylori infection. CONCLUSION: The diagnostic
      reproducibility of the urea breath test was very good.

PMID- 8540497
TI  - Physicians' perceptions of dysplasia and approaches to surveillance colonoscopy
      in ulcerative colitis.
AB  - OBJECTIVE: Colonoscopic biopsy surveillance to detect dysplasia, defined as a
      neoplastic change of the epithelium without invasion into the lamina propria, in
      patients with ulcerative colitis has become a widespread practice. We undertook a
      survey study to determine physicians' perceptions of, and approaches to,
      dysplasia surveillance colonoscopy in ulcerative colitis. METHODS: Members of two
      regional gastroenterology associations in the United States, including both
      academic and private practice-based gastroenterologists, and a group of senior
      gastroenterology trainees were surveyed by means of a written questionnaire. The
      questionnaires were distributed at three separate meetings of practicing
      gastroenterologists or trainees: 1) a Gastrointestinal pathology course for
      second-year gastroenterology fellows from training programs around the United
      States (February 1993, Los Angeles, CA); 2) a meeting of the Southern California
      Gastroenterology Society (March 1993, Los Angeles, CA); and 3) a meeting of the
      Pacific Northwest Gastroenterology Society (June 1993, Seattle, Washington). The
      percentages of all responses were tallied and analyzed for the group as a whole
      as well as by subgroup analysis. Understanding of the definition of dysplasia and
      specific practice techniques and approaches were the main outcomes sought.
      RESULTS: Only 19% of respondents correctly identified the definition of
      dysplasia. More respondents (48%) correctly defined high grade dysplasia
      specifically compared with only 16% who correctly defined low grade dysplasia.
      The majority of respondents (69%) recommended colectomy when high grade dysplasia
      was diagnosed, yet nearly one-third of respondents pursued continued surveillance
      in this setting. Almost uniformly, respondents pursued continued surveillance and
      not colectomy when low grade dysplasia was diagnosed. Nearly one-half of the
      respondents thought that there was only < 20% chance of finding invasive cancer
      in patients with preoperative diagnoses of high grade dysplasia. On average,
      respondents performed surveillance colonoscopy every 1-2 yr and took an average
      of three biopsies per site, at approximately eight sites in the colon, and most
      respondents confidently relied on their local pathologist at making the
      diagnosis. There were, however, wide variations in the practice of dysplasia
      surveillance. CONCLUSIONS: The majority of respondents did not know the
      definition of dysplasia, and most viewed it as a preneoplastic lesion.
      Furthermore, there was a lack of appreciation that the difference between low
      grade and high grade dysplasia is one of degree or severity of neoplastic change
      and for the likelihood of finding invasive cancer at surgery if there is only a
      diagnosis of dysplasia preoperatively. Dysplasia surveillance colonoscopy in
      ulcerative colitis is not a well standardized, clearly understood screening tool,
      and continued education of the gastroenterology community regarding its outcomes
      and pitfalls is needed.

PMID- 8540498
TI  - Psychological distress and seasonal symptom changes in irritable bowel syndrome.
AB  - OBJECTIVE: It is not known whether irritable bowel syndrome (IBS) fluctuates with
      the seasons. We aimed to determine whether seasonal changes in symptoms occur in
      IBS and to examine the relationships between IBS, seasonality, and psychological
      factors. METHODS: A random sample of the community (n = 99) and hospital staff
      volunteers (n = 163) in Sydney, Australia, completed a previously validated
      questionnaire that measured bowel symptoms, psychosocial factors, and
      seasonality. RESULTS: IBS (n = 60; 23%) was significantly associated with
      somatization (by the Psychosomatic Symptom Checklist) and lifetime depression but
      not neuroticism (by the Eysenck Personality Questionnaire) or psychological
      morbidity (by the General Health Questionnaire). A seasonal variation in behavior
      score (measuring sleep, eating, including carbohydrate craving, weight gain,
      socializing, energy level, and mood by the Seasonal Pattern Assessment
      Questionnaire) was associated with somatization (p < 0.001) and IBS (p < 0.05) in
      a stepwise multiple regression model. Of those with IBS, 23% reported moderate or
      greater seasonal change in bowel symptoms. Subjects with IBS (vs subjects with
      some bowel symptoms) were significantly more likely to report seasonal changes in
      pain and/or disturbed defecation (odds ratio = 3.2; 95% CI = 1.25-8.23); the
      latter was significantly associated with somatization but not the other
      psychological variables. CONCLUSIONS: A subset of IBS may be seasonally
      determined, and this is explained in part by somatization.

PMID- 8540499
TI  - Clinical outcome of post-ERCP pancreatitis: relationship to history of previous
      pancreatitis.
AB  - OBJECTIVE: The aim of this prospective study was to evaluate the relationship
      between clinical outcome of post-ERCP pancreatitis and history of previous
      pancreatitis. METHODS: Fifty patients (3.5%) developed procedure-related
      pancreatitis during the study period. Twenty-one patients had a history of
      previous pancreatitis (group I), and 29 patients had no history of previous
      pancreatitis (group II). There were no significant differences between the two
      groups with regard to age, gender, pancreatic duct injection, acinarization, or
      type of ERCP procedure. Grading of clinical severity was based on length of
      hospitalization, presence of pancreatic complications, and need for intervention:
      mild 28%, moderate 54%, and severe 18%. Four patients (8.0%) had pancreatic
      complications, but only one patient required surgery. There were no associated
      mortalities. RESULTS: Patients in group I had a shorter median hospital stay and
      were less likely to develop severe pancreatitis than patients in group II: 4.0
      versus 7.0 days, p = 0.001 and 4.8 versus 27.6%, p = 0.038, respectively.
      CONCLUSIONS: Intralobular and/or periductal fibrosis secondary to prior
      pancreatitis may limit the degree of ERCP-induced pancreatic acinar damage.

PMID- 8540500
TI  - Is ERCP necessary for symptomatic gallbladder stone patients before laparoscopic
      cholecystectomy?
AB  - OBJECTIVE: Laparoscopic cholecystectomy (LC) has become the choice of treatment
      for symptomatic gallbladder stones. The goal of this study was to predict the
      necessity for ERCP before LC using the noninvasive method of liver function
      testing (LFT) and sonography. METHODS: Before LC, 115 symptomatic gallbladder
      stone patients, whose diagnoses were confirmed by sonography, were studied by
      both LFT and ERCP. Patients who were already found to have either tumors or
      intrahepatic biliary stones on sonogram were excluded. Patients were classified
      into normal and dilated biliary tree groups by sonographic findings and normal
      and abnormal LFT (including bilirubin, alkaline phosphatase, gamma glutamyl
      transferase and amylase) groups. RESULTS: In patients with both normal biliary
      sonogram and LFT, 97.6% of patients had a negative ERCP study. Biliary tree
      dilation on sonogram had an 87% positive predictability for ductal pathology on
      ERCP (40/46). A normal biliary tree on sonogram had a 17.4% incidence of positive
      ductal pathology on ERCP (12/69). A single abnormal LFT equated to a 68.8%
      positive predictability for ductal pathology on ERCP. CONCLUSION: ERCP is not
      necessary before LC for patients with symptomatic gallbladder stones who have
      both a normal biliary tree on sonogram and normal LFT. A patient with either a
      dilated bile duct on sonogram or an abnormal liver function test does require
      ERCP study.

PMID- 8540501
TI  - Postsurgical bile leaks: endoscopic obliteration of the transpapillary pressure
      gradient is enough.
AB  - OBJECTIVES: Bile leaks are a well documented complication of biliary surgery,
      occurring more frequently with laparoscopic procedures. Endoscopic therapy with a
      long biliary endoprosthesis traversing the site of the leak is effective. We have
      evaluated the hypothesis that equalizing biliary and duodenal pressures with a
      short transpapillary stent is an equally effective therapy for bile leaks.
      METHODS: Thirty one consecutive patients presenting over a 52-month period with
      postsurgical bile leaks were evaluated. Patients had been treated with long
      endoprostheses (stents or nasobiliary tubes), sphincterotomy, or short
      transpapillary stents. The success, complication rate, need for additional
      therapy, and hospitalization time of each therapeutic approach were determined.
      RESULTS: Endoscopic therapy was successful in all 25 patients in whom a bile leak
      could be documented. The clinical success, need for radiological drainage, length
      of hospitalization, and incidence of pancreatitis were similar for all methods of
      treatment. CONCLUSIONS: These results confirm that endoscopic therapy is highly
      successful in the treatment of postoperative bile leaks and suggest that the
      mechanism of healing is the equalization of bile duct and duodenal pressures,
      allowing flow of bile into the duodenum. The endoscopic placement of short
      transpapillary stents without sphincterotomy is a temporary, effective, and
      technically simple method of pressure equalization. This should be considered as
      the primary therapy for most postoperative bile leaks.

PMID- 8540502
TI  - Clinical assessment of hyperlipidemic pancreatitis.
AB  - OBJECTIVE: This study addresses three questions: 1) What are the clinical
      presentations of pancreatitis secondary to hyperlipidemia? 2) What is the role of
      alcohol, diabetes, or known causes of hypertriglyceridemia? and 3) Does the
      course of pancreatitis secondary to hypertriglyceridemia differ from that of
      other etiologies? METHODS: We reviewed patients between 1982 and 1994 with a
      diagnosis of pancreatitis (577.0) and hypertriglyceridemia (272.0). Four
      hospitals participated. Seventy patients had a clinical presentation consistent
      with pancreatitis, that is elevated amylase and lipase or evidence of
      pancreatitis by ultrasound or CT imaging and serum triglyceride levels greater
      than 500 mg/dl or lactescent serum. Clinical data were derived from hospital
      admissions. RESULTS: Hypertriglyceridemia was the etiology in 1.3-3.8% of
      patients discharged with a diagnosis of pancreatitis. A history of diabetes
      mellitus was present in 72%, hypertriglyceridemia in 77%, alcohol use 23%, and
      gallstones in 7%. Lipemic serum was described on admission in 45%. Mean
      triglyceride levels were 4587 +/- 3616 ml/dl. Amylase was elevated two times
      normal in 54%, and lipase was elevated two times normal in 67%. CT scans were
      abnormal in 82%, with peripancreatic fluid in 34%, pseudocyst 37%, and necrosis
      in 15%. Abscess occurred in 13%, death in 6%. CONCLUSION: Acute pancreatitis
      secondary to hyperlipidemia is characterized by three presentations. All patients
      present with abdominal pain, nausea, and vomiting of hours to days duration. The
      most common presentation is a poorly controlled diabetic with a history of
      hypertriglyceridemia. The second presentation is the alcoholic found to have
      hypertriglyceridemia or lactescent serum on admission. The third, about 15-20% of
      patients, is the nondiabetic, nonalcoholic, nonobese patient with drug- or diet
      induced hypertriglyceridemia.

PMID- 8540503
TI  - Self-expanding metal stents for palliation of inoperable carcinoma of the
      esophagus and gastroesophageal junction.
AB  - OBJECTIVES: Rapid palliation of malignant dysphagia is usually possible with
      endoscopic implantation of plastic prosthesis, but this device has a high rate of
      complications. Recently expandable metal stents have become available that may
      have a reduced complications rate. METHODS: This report details our experience
      with 32 patients treated from September of 1992 through June of 1994. Twenty
      three patients were treated primarily with the Ultraflex esophageal prosthesis,
      and five patients were treated with postoperative malignant stricture, three with
      failed laser therapy and one with postradiation therapy malignant stricturing.
      Implantation was successful in 30/32 patients (94%). No major bleeding or
      perforation followed placement. The dysphagia score improved dramatically from 3
      to 0.5. Twenty-six patients had a follow-up of at least 30 days. No stent
      migration occurred. Food impaction was seen in three patients, tumor ingrowth in
      three, and overgrowth in one patient. The median survival was 6.2 months with a
      range of 1.8-11.3 months. CONCLUSIONS: Expandable metal stents are effective and
      safe for palliation of malignant obstruction of the esophagus and gastro
      esophageal junction. However, long term problems remain to be addressed, such as
      ingrowth by tumor, food impaction, and limitation of stent expansion by tumor
      rigidity.

PMID- 8540504
TI  - Treatment of esophageal fistulas with a new polyurethane-covered, self-expanding
      mesh stent: a prospective study.
AB  - OBJECTIVES: Esophagorespiratory fistulas are serious complications of malignant
      disease in the esophagus and are associated with rapid deterioration and death.
      Palliation has thus far consisted of insertion of a plastic stent to occlude the
      fistula opening. Insertion of these stents is associated with a high complication
      rate. Our aims were to study the efficacy of a new class of metal stents covered
      with a membrane with regard to fistula occlusion and lumen patency. METHODS: Six
      consecutive patients with esophagorespiratory fistulas were treated with covered
      expandable metal stents. RESULTS: In all six patients, no evidence of persisting
      fistula was seen on contrast radiographs 2 h after stent placement. All patients
      were able to eat a normal diet after stent insertion and had complete occlusion
      of their esophagorespiratory fistula. One patient reported pain after the
      procedure, and the symptoms persisted until death. One patient died of massive
      hematemesis 5 days after the procedure. Dysphagia scores improved in all patients
      from a median of 4 to a median of 1, and the Karnofsky score improved from a
      median of 40% to a median of 65%. Fistulas remained closed until death in all
      patients. CONCLUSIONS: Covered expandable metal stents are safe and effective in
      the palliation of esophagorespiratory fistulas.

PMID- 8540505
TI  - The surgeon's role in the treatment of chronic intestinal pseudoobstruction.
AB  - OBJECTIVE: The surgeon's role in the treatment of patients with chronic
      intestinal pseudoobstruction (CIP) is under-appreciated. Our aim was to determine
      the effects of operative treatment on symptomatic relief of CIP. METHODS: Records
      of all 21 patients who underwent surgery for CIP from 1980 to 1990 were reviewed.
      CIP was diagnosed by a combination of manometric, radiological, and/or
      histological examinations. RESULTS: Six of the nine patients who underwent
      resection or bypass of presumably localized disease are currently maintained on
      oral intake; one patient with multiple sclerosis who cannot eat is fed via a
      gastrostomy tube. Enterostomy tube(s) were placed in the other 12 patients; four
      no longer use the enterostomy tube(s), and eight rely on these decompressive tube
      enterostomies for symptomatic relief. After operative treatment, hospital
      readmissions decreased from a mean of 0.5 to 0.1 admission/year. All 19 patients
      currently alive report improved quality of life. CONCLUSIONS: Selective and
      directed operative treatment of patients with CIP can result in therapeutic and
      palliative benefits. The surgeon should have an active role in the evaluation and
      possible treatment of patients with CIP.

PMID- 8540506
TI  - Malignant transformation of benign epithelial gastric polyps.
AB  - OBJECTIVES: To compare the malignant potential of hyperplastic polyps and
      adenomas in relation to different histological classifications and to try to
      follow the natural history of the BEGP-carcinoma sequence. METHODS: During a 13
      yr period (1981-1993), 811 BEGP were discovered in 432 patients in consecutive
      esophagogastroscopic examinations in our department. Adequate endoscopic biopsies
      or polypectomy specimens were histologically diagnosed as hyperplastic polyp in
      751 (92.6%) and adenoma in 60 (7.4%) of the lesions, according to WHO
      classification. Hyperplastic lesions were further divided into two subgroups: 268
      were polypoid foveolar hyperplasia (FH) and 483 were typical hyperplastic polyps
      (HP), according to Elster's classification. Special attention was paid to focal
      malignancy at the first examination or malignant transformation of BEGP during
      follow-up. Ninety-six patients with 220 BEGP were followed for 1-11 yr, with an
      average of 2 yr and 8 months. RESULTS: According to Elster's classification,
      there were 10/483 (2.1%) HP and 6/60 (10.0%) adenomas with focal carcinoma.
      Moreover, in 19/265 patients (7.1%) with HP and in 4/30 patients (13.3%) with
      adenomas, carcinoma was found elsewhere in the stomach. During our follow-up,
      5/131 HP showed different steps of histological transformation: focal intestinal
      metaplasia in two, focal dysplasia in one, and focal carcinoma in two of them,
      which is 1.6%, 0.8%, and 1.6%, respectively. In 1/23 adenomas, focal carcinoma
      developed after 1 yr of observation (4.3%). Separate gastric carcinomas developed
      outside polyps during follow-up in 2/58 (3.5%) patients with hyperplastic polyps
      only. None of those with FH had focal carcinoma either at primary biopsy or
      during long-term observation. All proportions concerning gradual transformation
      of hyperplastic polyps classified as only one group according to WHO were lower.
      CONCLUSIONS: In contrast to hitherto existing opinions, our results give support
      to the idea that gastric HP, like adenomas, are susceptible to malignant
      transformation. It seems sensible to separate a subgroup of FH from HP, since FH
      have no malignant potential until they change their histology to HP. The
      treatment of FH and HP as one group is the main reason why the malignant
      potential of hyperplastic polyps is still underestimated.

PMID- 8540507
TI  - Colocare self-test versus Hemoccult II Sensa for fecal occult blood testing.
AB  - OBJECTIVES: To compare the efficacy of ColoCARE Self-Test pads against Hemooccult
      II SENSA, a traditional guaiac-based card test, in the screening for colorectal
      neoplasia. METHODS: Prospective crossover analysis of 102 high-risk patients for
      screening of colorectal neoplasia with fecal occult blood testing, using ColoCARE
      Self-Test pads and Hemoccult II SENSA cards. RESULTS: Sixty-eight of the 102
      patients (67%) had colorectal lesions diagnosed at colonoscopy. Of this group, 55
      patients (81%) had either a polyp or cancer diagnosed at colonoscopy, with 13 of
      these 55 patients having polyps > or = 1 cm. ColoCARE detected 21% of all
      lesions, compared with 72% for Hemoccult II SENSA. ColoCARE detected only 16% of
      cases involving either a cancer or a polyp, and 24% of cases involving either a
      cancer or polyp > or = 1 cm in size. This compares with 75% and 95%,
      respectively, for Hemoccult II SENSA. Significantly more patients preferred
      ColoCARE (84%) to Hemoccult II SENSA (5%) (p < 0.00001), and patients found it
      easier to use ColoCARE (p < 0.01). However, 33% of patients did not feel
      comfortable interpreting the ColoCARE results, and 29% found it difficult to
      interpret the color change. CONCLUSION: These results indicate that patients may
      prefer the simplicity and convenience of ColoCARE; however, the test is not
      sensitive for the detection of colorectal neoplasia. Furthermore, patients do not
      feel comfortable interpreting ColoCARE results and prefer to have fecal occult
      blood testing interpreted by medical personnel.

PMID- 8540508
TI  - Talc in the liver of patients with chronic hepatitis C infection.
AB  - OBJECTIVES: The presence of talc crystals in the liver has been associated with
      prior history of i.v. drug abuse (IVDA). Patients with hepatitis C virus (HCV)
      infection often deny IVDA, and many patients have no other identifiable risk
      factors. To evaluate the role of prior surreptitous IVDA in patients with chronic
      HCV infection and to assess the role of talc identification in liver tissue, an
      epidemiological evaluation was performed. METHODS: One hundred and nine patients
      with chronic HCV (ALT abnormal > 6 months, HCV ELISA and recombinant immunoblot
      assay positive) underwent careful evaluation for risk factors potentially
      associated with HCV infection. All patients then had liver biopsy. Liver biopsies
      were reviewed by two observers to determine histological stage and were then
      examined by polarized light microscopy to reveal the presence or absence of
      typical talc crystals. Patients with discordance between history and histological
      findings were re-interviewed and were confronted with the information. RESULTS:
      Patient interviews revealed the following risk factors: IVDA, 17.1%; blood
      transfusion, 24.3%; possible household/occupational exposure, 14.4%; and tattoos,
      15.3%. No identifiable risk factors were noted in 28.8% of the cohort. Talc
      crystals were seen in 9/109 (8.3%) of liver specimens. Of this group, only two
      patients admitted to prior history of IVDA. Seventeen patients with an IVDA
      history did not have identifiable talc crystals. Follow-up phone interviews were
      possible with five out of seven patients with liver talc who had previously
      denied IVDA history. Of the five patients, three admitted to prior IVDA but only
      after being confronted with the liver biopsy evidence. CONCLUSIONS: The findings
      of talc crystals in liver biopsy specimens appears to be a specific, but not a
      sensitive, marker for prior IVDA. Identification of talc crystals from liver
      tissue may contribute to categorization of risk factors in patients with
      community-acquired HCV infection. Tattoos are an important, and frequently
      unrecognized, risk factor for HCV infection. Despite these findings, a
      significant proportion of patients still have no identifiable risk factor for HCV
      acquisition.

PMID- 8540509
TI  - High prevalence of Helicobacter pylori antibodies in an institutionalized
      population: evidence for person-to-person transmission.
AB  - OBJECTIVE: To evaluate the prevalence of H. pylori antibodies in mentally and
      physically handicapped adults living together in a long-term care facility.
      METHODS: One hundred twenty-two institutionalized subjects from six living areas
      were compared to a normal representative Caucasian population obtained by random
      sampling from the urban population area of Melbourne. Serum samples from 1977 and
      1989 from 122 subjects were tested for H. pylori antibody by an ELISA technique.
      The data were analyzed by Student's t test, chi 2 test and logistic regression.
      RESULTS: Ninety-two of the 122 subjects (75%) from whom sera was collected in
      1989 were seropositive for H. pylori, compared with only 23% in age- and sex
      matched control subjects (p < 0.0001). The prevalence of H. pylori antibodies in
      1977 was 34% (42/122). Of the remaining 80 seronegative subjects, 51 (61.4%)
      converted to became positive in the 12-yr interval. The annual seroconversion
      rate was 7.4%, with an average of 4.25 newly positive subjects each year. The
      prevalence of H. pylori in 1989 was significantly higher than in 1977 after
      adjustment for age (odds ratio 2.39, 95% CI 1.1-5.3, p = 0.03). CONCLUSIONS: H.
      pylori antibodies are significantly more prevalent in institutionalized adults
      compared with controls from the general population. These data support the
      hypothesis that H. pylori is acquired by either fecal-oral or oral-oral
      transmission.

PMID- 8540510
TI  - Short- and long-term omeprazole for the treatment and prevention of duodenal
      ulcer, and effect on Helicobacter pylori.
AB  - OBJECTIVE: This study analyzes the effect of short- and long-term omeprazole (OM)
      on duodenal ulcer healing, recurrence, and H. pylori status. METHODS: Patients
      affected by active duodenal ulcer were randomly allocated to treatment with OM 20
      mg or 40 mg once daily for 4 wk. Subsequently, patients with healed duodenal
      ulcer were randomly assigned to one of the following three groups: OM 20 mg once
      daily for 12 months, OM 20 mg alternate days for 12 months, and no treatment.
      Endoscopy was performed at entry, at 4 wk, and after 4, 8, and 12 months. Two
      biopsy specimens from antrum, body, and fundus were taken for histology and
      search for H. pylori. One hundred and eighty patients with active duodenal ulcer
      were admitted. Ninety-one were treated with OM 20 mg once daily and 89 with OM 40
      mg for 4 wk. RESULTS: The results at 4 wk show 92.8% patients healed with OM 20
      mg and 95.1% at 40 mg (NS). In the second part of the study, 96 of the patients
      who healed at 4 wk (45 with OM 20 mg, and 51 with OM 40 mg) entered the long-term
      study. Thirty-six patients received OM 20 mg daily for 12 months, 35 OM 20 mg on
      alternate days for 12 months, and 25 patients no treatment. The results show a
      healing rate of 100%, 100%, and 95% with OM 20 mg daily, of 97%, 95%, and 93%
      with OM 20 mg on alternate days, and of 81%, 50%, and 40% (p < 0.01) with no
      treatment at 4, 8, and 12 months, respectively. H. pylori that was found in 97%
      of patients at entry, at 4 wk was found in 92.8% of patients treated with OM 20
      mg and in 97.5% of patients treated with OM 40 mg (NS). In one-third of the
      patients, H. pylori disappeared from the antrum but was found in the fundus. A
      30% reduction in the presence of H. pylori was seen in the group treated with 20
      mg daily for 12 months. CONCLUSIONS: We conclude that both continuous and
      alternate-day long-term OM treatment at 20 mg are similarly efficacious in the
      prevention of duodenal ulcer recurrence. Healing active duodenal ulcers with 20
      or 40 mg does not influence subsequent treatment. Long-term OM at 20 mg daily for
      12 months suppresses H. pylori temporarily in one-third of the patients. In these
      patients however, H. pylori reactivates after the end of treatment.

PMID- 8540511
TI  - Pouchitis disease course after orthotopic liver transplantation in patients with
      primary sclerosing cholangitis and an ileal pouch-anal anastomosis.
AB  - OBJECTIVE: Primary sclerosing cholangitis is associated with the development of
      pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. This study
      determined the effect of liver transplantation for primary sclerosing cholangitis
      on the disease course of pouchitis. METHODS: Seven patients with an ileal pouch
      anal anastomosis for ulcerative colitis underwent liver transplantation for
      primary sclerosing cholangitis. The medical record was reviewed to determine the
      pouchitis activity and pattern (no pouchitis, single acute, recurrent acute,
      chronic) before and after transplantation. RESULTS: Five of seven patients had
      pouchitis before transplant [recurrent acute (n = 3), chronic (n = 2)], and four
      of those five continued to have pouchitis after transplant (all chronic).
      Pretransplant sera were positive for antineutrophil cytoplasmic antibody in 6/6
      patients, compared to 5/6 patients posttransplant. One patient with pouchitis
      pretransplant became negative for antineutrophil cytoplasmic antibody
      posttransplant but continued to have pouchitis. CONCLUSION: Pouchitis occurs
      frequently in patients with primary sclerosing cholangitis and an ileal pouch
      anal anastomosis for ulcerative colitis. Liver transplantation does not alter the
      disease course of pouchitis for most of these patients.

PMID- 8540512
TI  - A noninvasive stable-isotope method to simultaneously assess pancreatic exocrine
      function and small bowel absorption.
AB  - OBJECTIVE: To determine if a single-step noninvasive stable isotope method of
      assessing digestive function could separate normal subjects from subjects with
      pancreatic insufficiency (maldigestion) or small bowel dysfunction
      (malabsorption) and to see if subjects with maldigestion could be simultaneously
      separated from subjects with malabsorption. METHODS: Forty (40) normal
      volunteers, 18 adults with cystic fibrosis and four adults with celiac sprue,
      ingested a liquid test meal along with bentiromide, [13C6]PABA, and xylose (PABAX
      test). Serum was collected at 1 h and analyzed for PABA, [13C6]PABA, and xylose
      by stable isotope dilution methods using gas chromatography mass spectrometry.
      RESULTS: All subjects with cystic fibrosis had abnormal pancreatic function test
      results, whereas three of four adults with sprue had normal values of pancreatic
      function. All subjects with sprue had abnormal small bowel absorption tests,
      whereas all adults with cystic fibrosis had apparently normal intestinal
      function. CONCLUSION: The one-step, 1-h PABAX test can reliably separate normal
      subjects from those with either maldigestion or malabsorption and can also
      separate subjects with maldigestion from those with malabsorption.

PMID- 8540513
TI  - Supplemental oxygen during endoscopic variceal ligation: effects on arterial
      oxygenation and cardiac arrhythmia.
AB  - OBJECTIVES: Endoscopic variceal ligation may affect cardiopulmonary function. The
      aim of this study was to determine the effect of either nasal oxygen (2 L/min) or
      no oxygen on arterial oxygenation and cardiac arrhythmia during variceal
      ligation. METHODS: A prospective, endoscopy team-blinded, randomized, cross-over
      study (first session vs second session) was conducted in 30 cirrhotic patients
      undergoing variceal ligation. Oxygen saturation (SaO2) and cardiac arrhythmia
      were assessed by a pulse oximeter. In this study, 15 patients received
      supplemental oxygen in the first sessions, and 15 received oxygen in the second
      sessions. RESULTS: Oxygen desaturation (nadir SaO2 < 90%) occurred in 23% of
      patients breathing room air but was prevented by oxygen (p < 0.01), and the nadir
      SaO2 was significantly lower in patients breathing room air than in those
      receiving oxygen (93.2 +/- 0.7% vs 98.3 +/- 0.3%, p < 0.01). During the
      procedure, premature ventricular contraction was more frequently observed in
      patients breathing room air than in those receiving oxygen (14.0 +/- 3.2/h vs 5.4
      +/- 1.5/r, p < 0.05). CONCLUSIONS: These data suggest that oxygen desaturation
      and cardiac arrhythmia are common in patients undergoing variceal ligation and
      that low flow nasal oxygen can alleviate these events. Supplemental oxygen is
      therefore advisable to avoid potential serious cardiopulmonary accidents in
      patients undergoing variceal ligation.

PMID- 8540514
TI  - A prospective comparison of laparoscopy and imaging in the staging of
      esophagogastric cancer before surgery.
AB  - OBJECTIVE: To carry out a prospective comparison of laparoscopy and combined
      imaging (CT and ultrasound) in the preoperative staging of distal esophageal and
      gastric cancer in patients who were selected for surgery. METHODS: Patients with
      clinically overt metastases or a contraindication to major surgery were excluded.
      One hundred and forty-five patients underwent chest radiography, CT of
      mediastinum and abdomen, and ultrasonography of abdomen and laparoscopy. The
      primary diagnoses were adenocarcinoma of the esophagogastric region in 110 cases,
      squamous cell carcinoma of the distal esophagus in 30 patients, and five
      miscellaneous. RESULTS: Thirty nine (27%) patients had metastatic disease outside
      the potential field of resection. Metastases were detected preoperatively by
      laparoscopy in 30 patients (sensitivity 77%) and by combined imaging in 15
      (sensitivity 38%) (p < 0.01). Twenty four patients with adenocarcinoma had
      metastases to the peritoneal cavity, which were detected preoperatively by
      laparoscopy in 23 (sensitivity 96%) and by combined imaging in five (sensitivity
      21%) (p < 0.01). Peritoneal metastases were not seen in patients with squamous
      cell carcinoma. Fifteen patients had hepatic metastases, which were detected
      preoperatively by laparoscopy in nine (sensitivity 60%) and by combined imaging
      in seven (sensitivity 47%). Laparoscopy was more sensitive than combined imaging
      in detecting metastases in patients with adenocarcinoma [laparoscopy 28, combined
      imaging 10 (p < 0.01)]. CONCLUSION: Addition of laparoscopy to the staging
      protocol prevented unbeneficial thoraco-abdominal exploration in 20 patients with
      adenocarcinoma. Thus, laparoscopy should be used in the assessment of patients
      with adenocarcinoma of the esophagogastric region before performing excisional
      surgery.

PMID- 8540515
TI  - Is radical surgery in locally advanced gallbladder carcinoma justified?
AB  - OBJECTIVES: Advanced gallbladder carcinoma is associated with a dismal long term
      prognosis. The aim of the present study was to evaluate the effectiveness of
      radical surgery in advanced stages of gallbladder carcinoma. METHODS: The course
      of 66 patients operated for advanced gallbladder carcinoma was evaluated in a
      retrospective study; 14% of patients had stage II, 29% had stage III, and 57% had
      stage IV tumors. Twelve patients underwent cholecystectomy (CHE) and
      lymphadenectomy of the hepatoduodenal ligament (LA); 17 patients underwent
      cholecystectomy combined with segment IV/V liver resection (CHE+LR) and LA; and
      10 patients underwent right extended hemihepatectomy (EHH). Complete tumor
      resection (R0) was achieved in six patients with CHE and LA, in 14 patients with
      CHE combined with segment IV/V LR and LA, and in all patients with right EHH.
      Resections with microscopic residual tumor (R1) were performed in nine patients.
      Mean follow-up was 15.4 months (range 3-90 months). RESULTS: The perioperative
      mortality rate was 1.5%, and the morbidity rate was 20%. In R0 resections, mean
      survival was 23.3, 25.0, and 26.3 months for the patients who underwent CHE and
      LA, CHE combined with segment IV/V LR and LA, and right EHH, respectively. After
      24 months, 46.4% of the patients with R0 resection were still alive compared with
      none of the patients with residual tumor. In the patients with R0 resection, no
      difference in survival was detected when node-negative status (pN0) was compared
      with positive locoregional lymph nodes (pN1a), whereas the degree of
      dedifferentiation (G2/G3) influenced survival. CONCLUSIONS: If complete resection
      is achieved, radical surgical procedures, including segment IV/V liver resection
      and extended right hepatectomy, significantly improve survival rates with an
      acceptable morbidity and mortality rate.

PMID- 8540516
TI  - Esophageal adenocarcinoma associated with Barrett's esophagus: long-term
      management with laser ablation.
AB  - We report the use of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser ablation to
      treat high-grade dysplasia and intramucosal esophageal adenocarcinoma associated
      with Barrett's esophagus in a patient who refused surgery. Throughout laser
      therapy, the patient received omeprazole 40 mg/day. After 1 1/2 yr, five laser
      treatments totaling 22,055 J given over a period of 13 months achieved squamous
      reepithelialization and absence of malignant transformation in the first area in
      which carcinoma was diagnosed. Squamous reepithelialization was maintained 1 yr
      later, confirming recent reports that photoablation plus omeprazole can achieve
      regression of Barrett's esophagus. During the last year of follow-up, a second
      contiguous area discovered to contain carcinoma was treated three times by
      photoablation, with a total of 13,164 J; biopsy showed only low-grade dysplasia
      in this area after two laser treatments totaling 8,108 J. No complications were
      seen during or after any of the laser sessions, and the patient remained
      asymptomatic 2 1/2 yr after the first photoablation and 3 yr after presentation.

PMID- 8540517
TI  - Gastroesophageal reflux-induced cough syncope.
AB  - Respiratory complications of gastroesophageal reflux disease that have been
      reported include hoarseness, wheezing, bronchospasm, stridor, laryngitis, and
      chronic cough. Syncope as a manifestation of gastroesophageal reflux disease
      induced cough has not been described in the literature. We present an unusual
      case of gastroesophageal reflux that resulted in frequent cough-induced syncope.
      Treatment ultimately consisted of a laparoscopic Nissen fundoplication which
      resulted in sustained relief from both cough and syncope.

PMID- 8540518
TI  - Fulminant hepatic failure as the initial manifestation of non-Hodgkins lymphoma.

PMID- 8540519
TI  - The black esophagus.
AB  - A dark-pigmented (black) esophagus is a rare observation during the course of
      upper endoscopy. The differential diagnosis of a black esophagus includes acute
      necrotizing esophagitis, exogenous dye ingestion, lye ingestion, malignant
      melanoma, melanosis, and pseudomelanosis esophagi. Many of these conditions are
      suggested by the history and associated endoscopic findings. In most patients, a
      biopsy is needed to establish a definitive diagnosis and explanation for the
      black-appearing esophagus. We describe a patient with a black esophagus
      encountered during routine endoscopy. The clinical, endoscopic, and
      histopathological features of this unusual finding are presented, along with a
      review of the literature.

PMID- 8540520
TI  - Early gastric carcinoma after gastrojejunostomy: clinical and pathological
      aspects.
AB  - Two rare cases of early gastric carcinoma that followed gastrojejunostomy without
      gastrectomy are reported. The time intervals between the initial
      gastrojejunostomy and resection of the distal stomach with the formation of a
      gastrojejunal stoma were 30 yr and 33 yr, respectively. The Japanese
      classification confirmed both lesions as type IIc type mucosal early gastric
      cancer. In these two cases, with coexisting gastric ulcers, atrophic gastritis
      and diffuse intestinal metaplasia were observed in the lesions of the carcinomas.
      The potential correlation between the exposure of tissue to duodenal juice and
      the subsequent development of a gastric carcinoma is discussed. Literature
      regarding gastric carcinoma after gastrojejunostomy is reviewed.

PMID- 8540521
TI  - Early detection of pancreatic glucagonoma.
AB  - Glucagonoma is a rare islet cell tumor of pancreas. Only 122 proven cases have
      been reported in the English literature so far. Diagnosis of glucagonoma has
      usually been delayed. The average size of clinically detected glucagonomas was
      5.8 cm, and 54.7% of them exhibited metastasis. We describe the case of a 0.7-cm
      asymptomatic pancreatic glucagonoma. A 45-yr-old female was demonstrated to have
      a demarcated, small, low echoic mass in the pancreatic head by routine
      ultrasonography. Table incremental dynamic computed tomography showed a small
      well-enhanced mass recognized only in an early phase. A 0.7 x 0.7 cm firm nodule
      on the pancreatic head was excised at operation. Immunohistochemical and
      ultrastructural studies revealed that this tumor was a glucagon-producing
      adenoma. This may be the smallest glucagonoma detected by image diagnostics that
      has been reported in the English literature. Possible early detection of
      glucagonoma was discussed in this report.

PMID- 8540522
TI  - Retention of nifedipine extended release tabs in a patient with a colonic
      stricture.

PMID- 8540523
TI  - Isolated tuberculosis of the pancreas masquerading as a pancreatic mass.
AB  - A 65-yr-old woman presented for evaluation of a pancreatic mass. She had been
      suffering from severe constitutional symptoms for 18 months; those symptoms
      included weight loss, increasing fatigue, night sweats, and recurrent fever
      attacks up to 40 degrees C. Later, bluish subcutaneous nodules developed on her
      lower limbs. Laboratory tests yielded signs of chronic inflammation and impaired
      glucose tolerance with elevated serum insulin and glucagon concentrations. Skin
      biopsy revealed lobular panniculitis. Ultrasonography and a CT scan demonstrated
      enlargement of the pancreas, and endoscopic retrograde pancreaticography
      disclosed displacement and stenosis of the main pancreatic duct. The patient was
      referred for explorative laparotomy, which was highly suggestive of a malignant
      pancreatic tumor. However, histological examination of the resected pancreatic
      and peripancreatic mass revealed tuberculous pancreatitis. This form of isolated
      tuberculous pancreatitis, associated with lobular panniculitis and laboratory
      features consistent with a tumor of the endocrine pancreas, has not been reported
      previously. Active tuberculosis should be a leading differential diagnosis in a
      patient with an enlarged pancreas when the usual diagnostic reasoning does not
      yield conclusive results.

PMID- 8540524
TI  - Enteroenteric intussusception: an unusual presentation of Crohn's disease in an
      adult patient.

PMID- 8540525
TI  - Pediatric rectal Dieulafoy's lesion.
AB  - Dieulafoy's lesions are an unusual cause of gastrointestinal hemorrhage. The
      overwhelming majority of lesions are found in the upper gastrointestinal tract,
      particularly along the lesser curvature of the stomach in the region supplied by
      the left gastric artery. Rectal Dieulafoy's lesions have never before been
      reported in the pediatric population, and our case represents only the third
      reported occurrence of a rectal Dieulafoy's lesion in the English medical
      literature. Successful treatment was administered, i.e., the combination of
      sclerotherapy followed by thermocoagulation. We therefore recommend that rectal
      Dieulafoy's lesion be included in the differential diagnosis of children with
      severe rectal bleeding and that management follow the same principles used to
      treat upper gastrointestinal tract Dieulafoy's lesions: injection therapy
      followed by heater probe coagulation.

PMID- 8540526
TI  - Macrolipasemia and celiac disease.
AB  - A case of undiagnosed celiac disease associated with macrolipasemia and
      macroamylasemia is reported. This association is almost unique. To our knowledge,
      only one case has been previously diagnosed. Previous case reports about
      macroamylasemia and celiac disease, as well as macrolipasemia, are briefly
      discussed.

PMID- 8540527
TI  - Aeromonas sobria infection with severe muscle degeneration in a patient with
      alcoholic liver cirrhosis.
AB  - A 56-yr-old male who had been followed for alcoholic liver disease was admitted
      for abdominal pain and a high fever. Gastrointestinal endoscopy revealed bleeding
      esophageal varices that were treated by endoscopic sclerotherapy. Blood culture
      on admission was positive for Aeromonas sobria. Then skin bullas and ulcers and
      severe muscle degeneration developed. The patient died despite extensive
      treatment with antibiotics. A. sobria infection in patients with liver cirrhosis
      is rare.

PMID- 8540528
TI  - Plesiomonas shigelloides: an unusual cause of diarrhea.

PMID- 8540529
TI  - AIDS and esophageal tuberculosis.

PMID- 8540530
TI  - Intrahepatic sequestered segment of liver presenting as focal fatty change.
AB  - Focal fatty change of the liver is a lesion that is often discovered on imaging
      studies and must be distinguished from space-occupying lesions. The pathogenesis
      is unknown. We report a lesion of focal fatty change in which the portal supply
      and biliary drainage were anomalous so that the lesion represents sequestered
      liver tissue. Because insulin favors the development of steatosis, the
      pathogenesis of focal fatty change could be explained if the aberrant portal
      supply contained more insulin than the main portal vein, as would occur if the
      portal supply arose from pancreatic veins via the parabiliary venous plexus of
      Couinaud. Furthermore, focal fatty sparing could be explained if the spared
      segment was supplied by veins draining from the stomach that carry blood with
      lower insulin levels than the main portal vein.

PMID- 8540532
TI  - "Cloggology" (unclogging pipes) revisited: radiologist to the rescue?

PMID- 8540531
TI  - Acute exacerbation of antiliver cytosol antibody-positive autoimmune chronic
      hepatitis by alpha-interferon.

PMID- 8540533
TI  - The night of the Iguana.

PMID- 8540534
TI  - Contrasting laporoscopic antireflux surgeries: is there a "best"?

PMID- 8540535
TI  - First description of the "migrating motor complex" and its physiological function
      in the human jejunum.

PMID- 8540536
TI  - Membranous obstruction of inferior vena cava causing Budd-Chiari syndrome.

PMID- 8540537
TI  - What is the meaning of ranitidine in successful triple-therapy against
      Helicobacter pylori infection?

PMID- 8540538
TI  - Dysphagia revealing esophageal and gastric metastases of renal carcinoma.

PMID- 8540539
TI  - Ammonia clearance as a rapid index of viability in liver transplantation.

PMID- 8540540
TI  - Mechanisms of pennicillamine and zinc in the treatment of Wilson's disease.

PMID- 8540541
TI  - The value of p-ANCA as a serological marker in diagnosing the coexistence of
      chronic active invasive amebic colitis and ulcerative colitis.

PMID- 8540542
TI  - A long-surviving case of gastric cancer with metachronous liver and lung
      metastases.

PMID- 8540543
TI  - Prevent Blindness America visual field screening study. The Prevent Blindness
      America Glaucoma Advisory Committee.
AB  - PURPOSE: To assess the screening efficacy and practical use of two portable
      devices to detect moderate to severe visual field loss rapidly in population
      screening. METHODS: Henson visual field analysis and Damato campimetry for
      glaucoma were performed in a healthy adult population, to determine false
      positive rates; in established glaucoma patients and suspects, to determine false
      negative rates; and in a general adult population, to assess practical use in
      actual screenings. RESULTS: There were no false-positive test failures among the
      82 normal subjects who completed the Henson two-step screening. Eighty of 83
      normal subjects passed Damato campimetry, resulting in a false-positive rate of
      3.6%. Among 83 glaucoma suspects and patients, the Henson test identified 49
      (84%) of 58 subjects whose full-threshold fields from Humphrey perimetry were
      abnormal, 38 (97%) of 39 of whom had moderate to severe visual field loss. The
      Damato campimeter detected 55 (81%) of 68 subjects with any pathologic loss on
      full-threshold visual fields, 44 (92%) of 48 of whom had moderate to severe
      visual field loss. Among 1,278 subjects tested in general population screenings,
      55 subjects (4.3%) failed either or both tests. CONCLUSIONS: The Henson visual
      field analyzer can discriminate moderately to severely diseased from normal
      visual fields with high sensitivity and specificity. The Damato campimeter can
      reliably detect moderate to severe visual field loss with a tolerably low false
      positive rate. To overcome the weakness of glaucoma screening by tonometry alone,
      some forms of visual field testing may be acceptably brief (cost effective) and
      accurate (sensitive and specific).

PMID- 8540544
TI  - Incidence of acute angle-closure glaucoma after pharmacologic mydriasis.
AB  - PURPOSE: To study the incidence of acute angle-closure glaucoma secondary to
      pupillary dilation and to identify screening methods for detecting angles at risk
      of occlusion. METHODS: We studied 5,308 respondents to the Baltimore Eye Survey,
      a cross-sectional, population-based survey conducted in a multiracial urban
      community. We measured incidence of acute angle-closure glaucoma after
      pharmacologic mydriasis and the specificity and sensitivity associated with three
      screening criteria in identifying those with potentially occludable angles. The
      screening factors were presence of shallow anterior chamber on penlight
      examination, history of glaucoma, and blindness. RESULTS: Of the 4,870 subjects
      whose eyes were dilated on screening examination, none developed acute angle
      closure glaucoma. However, 38 patients of the 1,770 who were referred for
      definitive eye examination were judged to have occludable angles on the basis of
      gonioscopic methods. Of note, subjects aged 70 years and more were three times
      more likely to have occludable angles than those aged 40 to 69 years (P < .004)
      In 14 black subjects with occludable angles, six were detected by history of
      glaucoma and not by shallow anterior chamber configuration; alternatively, in 24
      white subjects, 11 (46%) were detected on the basis of shallow anterior chambers
      (Fisher's exact test, P = .014). When the three screening factors were considered
      alone and in combination, the most effective combination for predicting a
      potentially occludable angle was to use shallow anterior chamber on penlight
      examination and history of glaucoma. These criteria provide 60.5% sensitivity and
      93.3% specificity. CONCLUSION: If screening is performed accurately and the
      results are negative, the risk of dilating a potentially occludable angle was
      less than one in 333 subjects (negative predictive value, 0.997) in this
      population.

PMID- 8540545
TI  - The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7.
      Results. Glaucoma Laser Trial Research Group.
AB  - PURPOSE: To determine differences between the two treatment groups of the
      Glaucoma Laser Trial with respect to intraocular pressure, visual fields, optic
      disk cupping, and therapy for primary open-angle glaucoma. METHODS: The Glaucoma
      Laser Trial was a multicenter, randomized clinical trial designed to assess the
      efficacy and safety of starting treatment for primary open-angle glaucoma with
      argon laser trabeculoplasty vs starting with topical medication. The Glaucoma
      Laser Trial Follow-up Study was a follow-up study of 203 of the 271 patients who
      enrolled in the Glaucoma Laser Trial. By the close of the Glaucoma Laser Trial
      Follow-up Study, median duration of follow-up since diagnosis of primary open
      angle glaucoma was seven years (maximum, nine years). RESULTS: Over the course of
      the Glaucoma Laser Trial and Glaucoma Laser Trial Follow-up Study, the eyes
      treated initially with argon laser trabeculoplasty had lower intraocular pressure
      and better visual field and optic disk status than their fellow eyes treated
      initially with topical medication. As compared to eyes initially treated with
      medication, eyes initially treated with laser trabeculoplasty had 1.2 mm Hg
      greater reduction in intraocular pressure (P < .001) and 0.6 dB greater
      improvement in the visual field (P < .001) from entry into the Glaucoma Laser
      Trial. The overall difference between eyes with regard to change in ratio of
      optic cup area to optic disk area from entry into the Glaucoma Laser Trial was 
      0.01 (P = .005), which indicated slightly more deterioration for eyes initially
      treated with medication. CONCLUSIONS: Initial treatment with argon laser
      trabeculoplasty was at least as efficacious as initial treatment with topical
      medication.

PMID- 8540546
TI  - Association between quantitative nerve fiber layer measurement and visual field
      loss in glaucoma.
AB  - PURPOSE: To evaluate the association between quantitative nerve fiber layer
      measurements and visual field loss in patients with primary open-angle glaucoma.
      METHODS: Quantitative retinal nerve fiber layer measurements were obtained in 53
      patients with primary open-angle glaucoma by using confocal scanning laser
      ophthalmoscopy (cross-section area) and confocal scanning laser polarimetry
      (retardation ratio). For each eye, three images were obtained with each
      instrument. An image that was the mean of those three was created and used in all
      analyses. We investigated the association between global, regional, and hemifield
      differences in retinal nerve fiber layer measurements and visual field loss with
      linear regression techniques. RESULTS: The retardation ratio decreased with
      increasing mean visual field loss, measured both globally and regionally; R2 (the
      amount of variation explained by the model) ranged from 8% to 21%. Retinal nerve
      fiber layer cross-section area was not significantly associated with global
      measures of visual field loss. The inferior visual field mean deviation increased
      with decreasing superior retinal nerve fiber layer cross-section area (R2 = 8.2%,
      P = .04); superior visual field mean deviation was not associated with inferior
      retinal nerve fiber layer cross-section area (R2 = 2.6%, P = .25). Hemifield
      differences in visual field mean deviation increased with increasing hemifield
      differences in retinal nerve fiber layer cross-section area (R2 = 20.0%, P <
      .001), but not with retardation ratio (R2 = 0.9%, P = .48). CONCLUSIONS:
      Quantitative measures of the retinal nerve fiber layer using both confocal
      scanning laser ophthalmoscopy and confocal scanning laser polarimetry were
      correlated with visual field loss in glaucoma patients.

PMID- 8540547
TI  - Calculation of intraocular lens power after radial keratotomy with computerized
      videokeratography.
AB  - PURPOSE: Because standard methods to determine intraocular lens power are not
      adequate in eyes that have had radial keratotomy, we undertook this study to
      evaluate the corneal power derived from computerized videokeratography for use in
      intraocular lens power calculations. METHODS: We examined four eyes of three
      patients who had radial keratotomy and who underwent phacoemulsification cataract
      surgery with implantation of a posterior chamber intraocular lens. We used a
      computerized videokeratography-derived corneal curvature value in the Holladay
      formula for intraocular lens calculations. We determined the ideal intraocular
      lens power and the keratometric value that would have led to the ideal
      intraocular lens power from the postoperative refraction at 6.1 +/- 1.1 months
      after cataract extraction. The ideal keratometric value was compared with the
      keratometric values derived from computerized videokeratography, standard
      keratometry, contact lens overrefraction, and refractions before and after radial
      keratotomy. RESULTS: The postoperative refraction at approximately six months
      averaged -0.32 +/- 0.63 diopter (range, -0.88 to +0.75 diopter) different than
      the aim. The mean power in ring 3, which was the closest keratometric value to
      the ideal, disclosed only 0.09 +/- 0.73 diopter and -0.10 +/- 0.72 diopter of
      deviation from the ideal keratometric and intraocular lens powers, respectively.
      One to two weeks after phacoemulsification cataract surgery with implantation of
      a posterior chamber intraocular lens, the videokeratographic differential map
      disclosed steepening at the wound site with variable regression by six months in
      all patients. CONCLUSION: Results suggest that, after radial keratotomy, using
      the keratometric value derived from computerized videokeratography in intraocular
      lens calculations is more accurate than using keratometric values measured by
      routine methods.

PMID- 8540548
TI  - Reversible loss of light perception after vitreoretinal surgery.
AB  - PURPOSE: We studied reversible loss of light perception after vitreoretinal
      surgery to show that functional vision can return in some patients. METHODS: We
      reviewed the medical records of seven patients who had postoperative reversible
      loss of light perception in the eye that underwent vitreoretinal surgery.
      Differences in the postoperative courses and interventions were studied. RESULTS:
      Five of the seven patients had diabetes mellitus but none had hypertension. The
      indications for vitreoretinal surgery were severe proliferative diabetic
      retinopathy in five patients and retinal detachment with advanced proliferative
      vitreoretinopathy in two patients. Seven patients had reversible loss of light
      perception within the first three postoperative days. Six of the seven patients
      had an intraocular pressure greater than 26 mm Hg at the time the eye had no
      light perception. Decreasing the intraocular pressure was associated with return
      of light perception in five of seven patients. Return of useful vision was
      gradual. Four of seven patients had a visual acuity of 20/400 or better one month
      after surgery, and all seven had a visual acuity of 20/400 or better three months
      after surgery. Visual acuity in four eyes improved further to 20/70 or better at
      six months or more after surgery. CONCLUSION: Reversible loss of light perception
      after vitreoretinal surgery does occur in some patients. Monitoring vision and
      intraocular pressure is important because prompt treatment may assist in the
      recovery of functional vision.

PMID- 8540549
TI  - A twin study of age-related macular degeneration.
AB  - PURPOSE: To determine the importance of genetic factors in age-related macular
      degeneration by using a twin study to compare the concordance of age-related
      macular degeneration in monozygotic and dizygotic twin pairs. METHODS: We
      prospectively examined 134 consecutive twin pairs and two triplet sets for age
      related macular degeneration. The zygosity was determined by genetic laboratory
      tests. RESULTS: The concordance of age-related macular degeneration was 100% (25
      of 25) in monozygotic and 42% (five of 12) in dizygotic twin pairs. The other
      twins or triplets had no macular changes of age-related macular degeneration.
      CONCLUSIONS: The statistically significant higher concordance of age-related
      macular degeneration in monozygotic than in dizygotic twin pairs and the clinical
      heterogeneity of age-related macular degeneration strongly suggest the importance
      of genetic and nongenetic factors, respectively, in age-related macular
      degeneration.

PMID- 8540550
TI  - Spontaneous resolution of foveal detachments and macular breaks.
AB  - PURPOSE: To evaluate the mechanism of spontaneous resolution of foveal
      detachments and idiopathic macular breaks. METHODS: We reviewed the records of
      139 consecutive eyes (94 patients) with either a foveal detachment or a macular
      break in patients who were examined between 1989 and 1992. There were 26 men and
      68 women (mean age, 66.9 +/- 6.9 years). They were either unoperated on or
      observed during the period that preceded surgery. Each patient underwent complete
      ophthalmic examination in addition to slit-lamp photography of the vitreomacular
      interface and microperimetry with the scanning laser ophthalmoscope. RESULTS:
      Eight eyes demonstrated spontaneous resolution. A foveal detachment was noted in
      five eyes (five patients) and a stage 2 macular break in three eyes (three
      patients). The mean duration of observation was 33 months (range, one to 144
      months). Resolution of the foveal detachments occurred without the development of
      posterior vitreous detachment. In each eye, the presence of a pseudo-operculum,
      indicating vitreofoveal separation, was accompanied by flattening of the foveal
      detachment without detectable posterior vitreous detachment. The three eyes with
      stage 2 macular break resolved after premature development of a posterior
      vitreous detachment. CONCLUSIONS: Foveal detachment and macular break resolution
      seem to result from the release or weakening of vitreous traction on the fovea.
      Reattachment of the foveal retina preserves fair to good visual acuity. Surgical
      intervention is contraindicated (1) in eyes in which foveal detachment flattens
      and develops a pseudo-operculum and (2) when a posterior vitreous detachment
      develops in an eye with a stage 2 macular break. Careful biomicroscopic vitreous
      examination and microperimetry with the scanning laser ophthalmoscope are
      extremely useful methods for adequate examination of these patients.

PMID- 8540551
TI  - Retinal arterial occlusions in young adults.
AB  - PURPOSE: To determine the cause, associated factors, visual results, and systemic
      morbidity in patients less than 40 years old with retinal arterial occlusions.
      METHODS: We studied 27 eyes with nontraumatic retinal arterial occlusions in 21
      patients less than 40 years old (range, 22 to 38 years; mean, 28 years). RESULTS:
      Of the 21 patients, branch retinal artery (arteriolar) occlusion occurred in 15
      (71%), central retinal artery occlusion occurred in five (24%), and cilioretinal
      artery occlusion occurred in one (5%). Retinal artery occlusions were bilateral
      in six patients (29%) and occurred in 14 women (67%). Emboli were identifiable in
      seven patients (33%). Cardiac valvular disease was the most commonly recognized
      etiologic agent and was present in four patients (19%). Various associated
      factors leading to a hypercoagulable state or embolic condition were identified
      in 19 patients (91%). CONCLUSION: Retinal arterial occlusions in young adults
      occur via multiple mechanisms. Systemic evaluation allows detection of a risk
      factor for retinal arterial occlusive disease in most patients.

PMID- 8540552
TI  - Streptococcal gangrene of the eyelids and orbit.
AB  - PURPOSE: Streptococcal gangrene, also termed streptococcal necrotizing fasciitis,
      is resurgent but remains exceedingly rare. Ophthalmologists and dermatologists
      must be aware of streptococcal gangrene, as eyelids are the most commonly
      affected area of the head and neck. METHODS: We studied two cases of
      streptococcal gangrene of the orbit with clinical manifestations
      indistinguishable from common nonnecrotizing orbital cellulitis. RESULTS:
      Infection progressed with dramatic rapidity to produce eyelid necrosis,
      respiratory failure, sepsis, and severe permanent visual loss caused by
      ophthalmic artery occlusions. Histopathologic analysis disclosed vascular
      thrombosis, necrosis, acute inflammation, and the presence of gram-positive
      cocci. Cultures grew heavy group A beta hemolytic Streptococcus. The first
      patient was infected with M type 1 carrying exotoxins A and B. The second patient
      was also infected with Streptococcus carrying exotoxin A. CONCLUSION: Early
      diagnosis of this life-threatening infection is of paramount importance because
      survival may depend on early surgical debridement.

PMID- 8540553
TI  - The challenge of screening for glaucoma.

PMID- 8540554
TI  - Serous retinal detachment of the macula associated with cat scratch disease.
AB  - PURPOSE: We studied an unusual ocular manifestation of cat scratch disease.
      METHODS: We examined a patient who had a serous retinal detachment of the macula
      with vision loss out of proportion to her retinal findings. RESULTS: The patient
      was found to have cat scratch disease by antibody titers. CONCLUSION: Cat scratch
      disease should be considered in patients with a serous neurosensory retinal
      detachment of the macula and a history of cat exposure or systemic signs or
      symptoms consistent with the disease.

PMID- 8540555
TI  - Fluorescein labeling of tissue plasminogen activator for subretinal thrombolysis.
AB  - PURPOSE: To assess a technique that facilitated the use of tissue plasminogen
      activator in the dissolution and evacuation of subretinal blood. METHODS:
      Fluorescein dye was added to the tissue plasminogen activator solution before
      subretinal injection. RESULTS: Labeling tissue plasminogen activator solution
      with fluorescein made the solution easily visible, enhancing the ability of the
      surgeon to assess clot lavage, detect reflux into the vitreous cavity, and judge
      the extent of clot dissolution. CONCLUSIONS: Adding fluorescein dye to tissue
      plasminogen activator solution is simple and gives the surgeon added control of
      clot lysis.

PMID- 8540556
TI  - Coloboma of the optic disk associated with retinal vascular abnormalities.
AB  - PURPOSE: We studied a case of congenital optic disk pit and coloboma with
      associated malformations of the retinal vessels. METHODS: Slit-lamp biomicroscopy
      and fluorescein angiography were performed. RESULTS: Multiple retinal venous
      anastomoses associated with a congenital coloboma and pit of the optic disk were
      observed. The retinal vascular anomalies extended from the optic disk to the
      temporal periphery. CONCLUSIONS: We consider the coexistence of retinal venous
      anastomoses with optic disk coloboma and pit to be an extremely rare congenital
      retinal anomaly.

PMID- 8540557
TI  - Air bag-related corneal rupture after radial keratotomy.
AB  - PURPOSE: We studied a case of air bag-associated corneal rupture in a patient who
      had previously undergone radial keratotomy surgery. METHODS: The patient was
      struck in the right eye when his driver's side air bag inflated during a low
      speed collision. RESULTS: Inflation of the air bag resulted in rupture of the
      patient's right cornea. The rupture involved all but one of his old radial
      keratotomy wounds. CONCLUSIONS: Patients who have undergone radial keratotomy may
      be at increased risk for corneal rupture caused by air bag trauma. These patients
      may benefit by wearing protective eyewear while driving cars equipped with air
      bags.

PMID- 8540558
TI  - Disappearance of crystals in Schnyder's crystalline corneal dystrophy after
      epithelial erosion.
AB  - PURPOSE: A 40-year-old woman with Schnyder's crystalline corneal dystrophy had
      two episodes of epithelial erosion. METHODS: We reviewed the patient's medical
      record and photographic file. RESULTS: In the areas underlying the epithelial
      erosion, the crystalline opacities disappeared. The crystals recurred in the
      subsequent five years but were not as dense. CONCLUSIONS: Crystals in the
      subepithelial or Bowman's layer may lead to epithelial destabilization and
      corneal epithelial erosion. Disappearance of the crystalline opacities may occur
      after disruption of the epithelium.

PMID- 8540559
TI  - Inadequately irradiated solitary extramedullary plasmacytoma of the orbit
      requiring exenteration.
AB  - PURPOSE: To emphasize that solitary orbital extramedullary plasmacytoma, a rare
      tumor, is not invariably radiosensitive. METHOD: We examined a patient who had
      undergone empirical irradiation that failed to control an orbital tumor. RESULTS:
      After a second biopsy had secured the diagnosis of a solitary extramedullary
      plasmacytoma, further irradiation proved ineffective and exenteration was
      required. The patient was free of recurrence one year after exenteration and had
      satisfactory cosmesis with a prosthesis. CONCLUSION: A histologic diagnosis is
      essential before treatment is commenced so that the correct radiation dosage is
      used.

PMID- 8540560
TI  - Color Doppler imaging and spectral analysis of the optic nerve vasculature in
      glaucoma.

PMID- 8540561
TI  - The effect of povidone-iodine solution applied at the conclusion of ophthalmic
      surgery.

PMID- 8540562
TI  - Reappraisal of biomicroscopic classification of stages of development of a
      macular hole.

PMID- 8540563
TI  - Lifetime perturbations of bipolar disorder.

PMID- 8540564
TI  - The thalamus as a site of action of antipsychotic drugs.
AB  - OBJECTIVE: Because recent data suggest that there are abnormalities of the
      thalamus in schizophrenia, the authors tested the effects of antipsychotic drugs
      on thalamic sites. METHOD: Nine rats were given acute doses of the typical
      neuroleptic haloperidol (N = 3), the atypical neuroleptic clozapine (N = 3), or a
      drug-free vehicle (N = 3). Cellular activation was assessed by using
      immunohistochemistry to determine expression of the immediate response gene c
      fos. RESULTS: Both antipsychotic drugs induced increased Fos immunoreactivity,
      suggesting increased activity in cells of the midline nuclei of the thalamus.
      CONCLUSIONS: The shared clinical effects of antipsychotic drugs may be mediated
      in part through actions on the thalamus.

PMID- 8540565
TI  - Linkage study of the D5 dopamine receptor gene (DRD5) in multiplex Icelandic and
      English schizophrenia pedigrees.
AB  - OBJECTIVE: The authors investigated the possibility that genetic variation or
      mutation of the dopamine D5 receptor gene might modify susceptibility to
      schizophrenia. METHOD: Twenty-three Icelandic and English pedigrees containing
      multiple cases of schizophrenia were genotyped by using a highly informative
      microsatellite for the D5 dopamine receptor gene DRD5. RESULTS: By means of three
      different affection models, negative lod scores were obtained under assumptions
      of autosomal dominant and recessive inheritance. There was no evidence for locus
      heterogeneity. Nonparametric extended relative pair analysis also produced
      negative results. CONCLUSIONS: These data indicate that mutations of the D5
      dopamine receptor gene are not a major cause of schizophrenia in these pedigrees.
      Because of the probable existence of locus heterogeneity, the D5 receptor gene
      may be of etiologic importance in other families with schizophrenia.

PMID- 8540566
TI  - Parenting: a genetic-epidemiologic perspective.
AB  - OBJECTIVE: To understand the relation between parenting and later
      psychopathology, it is important to clarify the role of genetic and environmental
      factors in both the elicitation and the provision of parenting behavior. METHOD:
      A 16-item version of the Parental Bonding Instrument was administered to 1) 606
      fathers and 848 mothers of an epidemiologic sample of adult female-female twin
      pairs, who reported on their parenting of their twins; 2) the twins (both members
      of 546 monozygotic and 390 dizygotic pairs), who reported on the parenting they
      had received from their father and mother; 3) co-twins from these pairs, who
      reported on the parenting provided by their father and mother to their twin
      sister; and 4) members of the adult twin pairs (145 monozygotic and 117
      dizygotic) who both had children, who reported on the parenting they provided to
      their offspring. The data were subjected to model fitting decomposing three
      sources of variance: additive genetic factors; family, or common, environment;
      and an individual's unique environment. RESULTS: Responses to the Parental
      Bonding Instrument produced three factors: parental warmth, protectiveness, and
      authoritarianism. According to parents, these factors were largely a common
      environmental experience for their children. Responses from twins, however,
      indicated that genetic factors played a substantial role in the elicitation of
      warmth from parents and a more modest role in influencing parental protectiveness
      and authoritarianism. While reports of twins and co-twins on protectiveness and
      authoritarianism yielded similar results, analysis of responses from co-twins
      indicated a degree of importance of genetic factors in eliciting parental warmth
      which was midway between that from parents' reports and twins' reports. Answers
      from twins as parents indicated that provision of warmth was substantially
      heritable, while resemblance between twins in providing protectiveness and
      authoritarianism was due to family environment. CONCLUSIONS: The provision of
      parenting is influenced by attitudes derived from the parent's family of origin
      as well as by genetically influenced parental temperamental characteristics. The
      elicitation of parenting is influenced by temperamental traits of the offspring
      that are, in turn, under partial genetic control. Genetic factors in both parent
      and child are more important for warmth than for protectiveness or
      authoritarianism.

PMID- 8540567
TI  - Prevalence of panic in patients referred for pulmonary function testing at a
      major medical center.
AB  - OBJECTIVE: The authors examined the prevalence and correlates of panic disorder
      in a group of patients who were referred for pulmonary function testing. METHOD:
      Patients (N = 115) were screened for the presence of panic attacks and panic
      disorder with a self-report questionnaire; a subgroup (N = 25) received
      structured diagnostic assessment. RESULTS: Of the 115 patients, 41% (N = 47)
      reported panic attacks and 17% (N = 20) met screening criteria for panic
      disorder. From the confirmed rate of panic disorder among the subgroup who
      received structured diagnostic assessment, the overall prevalence rate of panic
      disorder was estimated to be 11% and included six of the nine patients (67%) who
      had a diagnosis of chronic obstructive pulmonary disease. There were no
      significant differences between patients with and without panic in the severity
      of pulmonary function abnormalities or in the response to bronchodilators.
      However, patients with panic attacks were significantly more likely to report
      dyspnea at rest and irritable bowel symptoms and tended to report difficulty
      swallowing. CONCLUSIONS: This study suggests that panic disorder and subsyndromal
      panic are relatively common and may be unrecognized and inadequately treated in
      patients who present with respiratory symptoms.

PMID- 8540568
TI  - Elevated plasma levels of neuropeptide Y in patients with panic disorder.
AB  - OBJECTIVE: Neuropeptide Y is a pancreatic polypeptide closely associated with
      noradrenergic activity both in the central and peripheral nervous systems. The
      objective of this study was to assess plasma neuropeptide Y-like immunoreactivity
      in panic disorder. METHOD: Radioimmunoassays were performed in 12 patients with
      DSM-III-R panic disorder and two groups of normal comparison subjects (N = 22 and
      N = 16). RESULTS: Markedly higher plasma neuropeptide Y-like immunoreactivity was
      found in patients with panic disorder. CONCLUSIONS: Higher plasma neuropeptide Y
      like immunoreactivity suggests that this peptide may be implicated in the
      etiology or expression of symptoms of panic disorder.

PMID- 8540569
TI  - Prevalence of borderline personality symptoms in two groups of obese subjects.
AB  - OBJECTIVE: The purpose of this study was to compare the prevalence of borderline
      personality symptoms and self-harm behavior in two distinct groups of obese
      subjects. METHOD: Obese women, 17 from an eating disorders program and 60 from a
      primary care setting, were administered the borderline personality scale of the
      Personality Diagnostic Questionnaire--Revised, the Diagnostic Interview for
      Borderline Patients, and the Self-Harm Inventory. RESULTS: There was a
      significant between-group difference on all study measures, with subjects in the
      eating disorders program displaying more psychopathology. CONCLUSIONS: Study
      group membership appears to have a significant effect on the prevalence of
      psychopathology in obese women.

PMID- 8540570
TI  - Pathological gambling and platelet MAO activity: a psychobiological study.
AB  - OBJECTIVE: The authors studied platelet monoamine oxidase (MAO) activity and
      psychological characteristics of male pathological gamblers. METHOD: Twenty-seven
      male pathological gamblers were compared with a group of healthy individuals who
      were matched by age, sex, and tobacco consumption. Measures included platelet MAO
      activity and scores on the MMPI and Zuckerman's Sensation Seeking Scale. RESULTS:
      Platelet MAO activity and scores on several MMPI scales for the two groups were
      significantly different, but measures of sensation seeking were not. No
      correlations of biological significance were found between platelet MAO activity
      and psychological ratings. CONCLUSIONS: Low platelet MAO activity may be a
      biological predisposition for impulsivity in pathological gamblers. Although no
      psychological pattern is characteristic of pathological gamblers, they differ
      from healthy individuals in some personality traits. No significant relationship
      could be established between platelet MAO activity and psychological measures.

PMID- 8540571
TI  - Nicotine toxicity misdiagnosed as lithium toxicity.

PMID- 8540572
TI  - Respiridone and mania.

PMID- 8540573
TI  - Treating compulsive self-mutilation in a mentally retarded patient.

PMID- 8540574
TI  - Therapeutic effect of clozapine at an unusually high plasma level.

PMID- 8540575
TI  - Recurrent hyponatremia associated with fluoxetine and paroxetine.

PMID- 8540576
TI  - To sleep--perchance to dream ... of affective disorders.

PMID- 8540577
TI  - Cardiac effects of haloperidol and carbamazepine treatment.

PMID- 8540578
TI  - SSRI treatment of depression with comorbid cardiac disease.

PMID- 8540579
TI  - Patients' preferences for sex of therapist.

PMID- 8540580
TI  - Combining risperidone with standard neuroleptics for refractory schizophrenic
      patients.

PMID- 8540581
TI  - Where have two DSM revisions taken us for the diagnosis of pain disorder in
      chronic pain patients?

PMID- 8540582
TI  - Reliability of the SANS.

PMID- 8540583
TI  - Relationship between alcohol problems and anxiety disorders.

PMID- 8540584
TI  - Treatable risk factor for osteoporosis?

PMID- 8540585
TI  - Validating psychiatric diagnoses.

PMID- 8540586
TI  - Antecedents and consequences of negative life events in adulthood: a longitudinal
      study.
AB  - OBJECTIVE: This study investigated whether negative life events affected
      subjects' long-term physical and mental health. METHOD: One hundred thirteen
      normal college men completed biennial follow-up questionnaires from age 26 until
      age 62. At age 62 they retrospectively assessed 16 major negative life events
      with a self-report checklist. A blind rater read each man's complete records over
      the 35 years and completed the same checklist prospectively. The men had
      independent physical examinations at age 65. RESULTS: It was demonstrated that
      negative life events affect men's psychological health more than their physical
      health. The correlation of negative life events with physical health was so low
      that no significant relationship between the two variables could be established.
      Negative life events were significantly associated with affective spectrum
      disorder and its relevant indicators. Further, the Cox proportional hazards model
      revealed that negative life events, family history of depression, and
      psychosocial stability during the college years were independent and
      statistically significant predictors of depression. CONCLUSIONS: This study
      supports the widely held belief that biological factors (heredity), psychological
      factors (unstable personality), and social factors (negative life events) are all
      etiologically related to depression.

PMID- 8540587
TI  - Homosexuality in men and number of older brothers.
AB  - OBJECTIVE: This study investigated whether homosexual men have a higher mean
      birth order than heterosexual men primarily because they have more older brothers
      or because they have more older siblings of both sexes. METHOD: For the main
      analyses, 302 heterosexual men were individually matched on year of birth with an
      equal number of heterosexual men. Each completed a self-administered, anonymous
      questionnaire concerning family background and other biodemographic information.
      RESULTS: Logistic regression analysis showed that homosexuality was positively
      correlated with the proband's number of older brothers but not with older
      sisters, younger brothers, younger sisters, or parental age at the time of the
      proband's birth. Each additional older brother increased the odds of
      homosexuality by 33%. CONCLUSIONS: These results restrict the range of possible
      theories of the birth order phenomenon to those that can explain not only why
      older brothers increase the probability of homosexuality in later-born males but
      also why older sisters neither enhance this effect nor counteract it.

PMID- 8540588
TI  - Seed or soil: how does our garden grow?

PMID- 8540589
TI  - Visual cortical dysfunction in Alzheimer's disease evaluated with a temporally
      graded "stress test" during PET.
AB  - OBJECTIVE: Visual-processing abnormalities commonly contribute to typical
      Alzheimer's disease symptoms, but their detailed pathophysiology remains unknown.
      To investigate why patients with Alzheimer's disease have greater difficulty
      performing visuoconstructive (magnocellular-dominated) tasks than face- or color
      perception (parvocellular-dominated) tasks, the authors measured brain activation
      in response to a temporally graded visual stimulus (neural stress test) during
      positron emission tomography. METHOD: The stress test measured regional cerebral
      blood flow (CBF) in response to a patterned flash stimulus in the resting state
      (0 Hz in the dark) and at frequencies of 1, 2, 4, 7, and 14 Hz. Ten patients with
      Alzheimer's disease and 12 age- and sex-matched comparison subjects were studied.
      RESULTS: The striate response at 7 Hz and 14 Hz (the degree of regional CBF
      increase from that at 0 Hz) was significantly less in the patients than in the
      comparison subjects, whereas the change in regional CBF at the lower frequencies
      did not differ between groups. In bilateral middle temporal association areas
      activated by motion and dominated by magnocellular input, regional CBF at 1 Hz
      (the frequency with maximal apparent motion) was significantly greater than at 0
      Hz in the comparison subjects but not in the patients. CONCLUSIONS: The
      magnocellular visual system normally responds to high-frequency input and motion;
      the failure of response in the striate cortex at high but not low frequencies in
      the Alzheimer's patients suggests greater magnocellular than parvocellular
      dysfunction at these levels. Activation failure in the middle temporal areas in
      the patients supports magnocellular dysfunction. The finding that the Alzheimer's
      disease group had abnormal visual cortical function emphasizes the importance of
      clinical visuospatial evaluation of patients with Alzheimer's disease to fully
      understand symptom production and to plan interventions.

PMID- 8540591
TI  - Superior temporal gyrus volume in schizophrenia: a study using MRI morphometry
      assisted by surface rendering.
AB  - OBJECTIVE: Interpretation of the literature concerning superior temporal gyrus
      volume in patients with schizophrenia is complicated by methodological variation
      between studies and by the difficulty of identifying gyral boundaries in serial
      sections. METHOD: With the aid of three-dimensional cortical renderings, the
      authors developed a morphometric approach in which information from the cortical
      surface is incorporated into gyral boundary decisions. Using this technique, they
      assessed superior temporal gyrus volume in young, right-handed male patients with
      schizophrenia and in right-handed male comparison subjects. They also compared
      their technique with existing slice-based morphometric methods by using
      previously reported subcortical landmarks to define the gyral boundaries.
      RESULTS: There was no significant main effect of diagnosis and no significant
      diagnosis-by-hemisphere interaction. Significant leftward laterality was present
      only among comparison subjects. Leftward superior temporal gyrus laterality did
      not correlate with leftward laterality of the planum temporale. No significant
      reduction in superior temporal gyrus volume was revealed in the patients. No
      significant leftward laterality was detected with the slice-based technique,
      suggesting that a significant portion of superior temporal gyrus tissue is
      omitted with this approach. The lack of findings could not be explained by a
      general absence of morphometric abnormalities in this group of subjects because
      the patients had significantly larger lateral ventricles. CONCLUSIONS:
      Significant reduction in the superior temporal gyrus volume was not confirmed in
      this group of patients with schizophrenia, probably because of the small effect
      size of this finding. Methodological variation is an important factor in
      determining superior temporal gyrus volume on magnetic resonance imaging scans.

PMID- 8540590
TI  - Functional sites of neuroleptic drug action in the human brain: PET/FDG studies
      with and without haloperidol.
AB  - OBJECTIVE: The functional pathways through which antipsychotic drugs act in the
      brain to decrease psychosis remain unknown, despite our knowledge that their site
      of initial action is through blockade of dopamine D2 receptors. The authors
      sought to define the brain regions that are functionally altered by neuroleptic
      drugs. METHODS: Regional cerebral glucose metabolism was studied in 12 subjects
      with schizophrenia while they were receiving a fixed dose of haloperidol, again 5
      days after withdrawal of the drug, and a third time 30 days after withdrawal.
      Positron emission tomography with an [18F]fluorodeoxyglucose tracer was used in a
      within-subject design. RESULTS: The analysis demonstrated a decrease in glucose
      metabolism in the caudate and putamen 30 days after withdrawal, indicating that
      haloperidol treatment enhanced glucose utilization in these areas. The thalamus,
      bilaterally but only in anterior areas, showed the same response to haloperidol.
      Only in the frontal cortex and in the anterior cingulate had metabolism increased
      30 days after withdrawal, indicating that in those two cortical areas haloperidol
      depressed glucose metabolism. In the 5-day drug free scans, no regions differed
      significantly from those in the haloperidol condition, despite numerical changes.
      CONCLUSIONS: It appears that 5 days of neuroleptic withdrawal are inadequate to
      escape the effects of neuroleptic drugs on regional cerebral glucose metabolism.
      The pattern and localization of changes in metabolic activity between the
      haloperidol condition and the 30-day drug-free condition suggest that haloperidol
      exerts its primary antidopaminergic action in the basal ganglia. It is proposed
      that the additional changes in the thalamus and cortex are secondary to this
      primary site of drug action, mediated through classically described striato
      thalamo-cortical pathways.

PMID- 8540592
TI  - Psychodynamics and psychiatric diagnoses of pseudoseizure subjects.
AB  - OBJECTIVE: The goal of this study was to determine current and lifetime rates of
      DSM-III-R disorders in patients with pseudoseizures and to ascertain whether
      trauma is associated with the occurrence of pseudoseizures. METHODS: Adult
      pseudoseizure patients (N = 45) were interviewed regarding seizure course and
      life events, and they were given the Structured Clinical Interview for DSM-III-R-
      Patient Version, the Structured Clinical Interview for DSM-III-R Dissociative
      Disorders, the Dissociative Experiences Scale, and the Personality Diagnostic
      Questionnaire--Revised. The pseudoseizures were diagnosed in a tertiary-care
      video-EEG facility. Most of the subjects (78%) were female, and the mean age of
      the overall patient group was 37.5 years (SD = 9.7). RESULTS: The mean duration
      of the subjects' seizure history was 8.3 years (SD = 8.0). Common current
      psychiatric diagnoses included somatoform disorders (89%), dissociative disorders
      (91%), affective disorders (64%), personality disorders (62%), posttraumatic
      stress disorder (PTSD) (49%), and other anxiety disorders (47%). The lifetime
      occurrence of nonseizure conversion disorders was 82%. The mean Dissociative
      Experiences Scale score was 20.2 (SD = 18.2). Trauma was reported by 84% of the
      subjects: sexual abuse by 67%, physical abuse by 67%, and other traumas by 73%.
      CONCLUSIONS: Pseudoseizure subjects have high rates of the psychiatric disorders
      found in traumatized groups; they closely resemble patients with dissociative
      disorders. Reclassification of conversion seizures with the dissociative
      disorders should be considered. Pseudoseizures often appear to express distress
      related to abuse reports. Clinicians should screen pseudoseizure patients for
      adult and childhood trauma, dissociative disorders, depression, and PTSD.

PMID- 8540593
TI  - PET and the [15O]H2O technique, Part 2: Choosing a significance threshold.

PMID- 8540594
TI  - Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic
      stress disorder.
AB  - OBJECTIVE: Exaggerated startle reflex is reputed to be one of the cardinal
      symptoms of posttraumatic stress disorder (PTSD). The goal of this study was to
      assess the magnitude of the acoustic startle reflex in Gulf War veterans with
      PTSD. METHOD: The eye-blink component of the startle reflex was measured in
      response to six blocks of pseudorandomized 40-msec white noise bursts of varying
      intensities (90, 96, 102, 108, and 114 dB) in 10 Gulf War veterans with PTSD,
      seven Gulf War veterans without PTSD, and 15 civilian subjects without PTSD.
      RESULTS: The magnitude of the first startle response, as well as the magnitude of
      startle response averaged across blocks of testing, was significantly greater in
      Gulf War veterans with PTSD than in veteran and civilian comparison groups.
      CONCLUSIONS: Consistent with some clinical studies investigating the startle
      response in Vietnam veterans with PTSD, this investigation provides evidence for
      exaggerated startle response in this disorder. Preclinical studies of shock
      sensitization of the startle response suggest that the higher levels of startle
      response seen in the PTSD subjects may reflect a sensitization of the fear/alarm
      response created by the stress of combat trauma.

PMID- 8540595
TI  - Hypothalamic-pituitary-adrenal axis activity in panic disorder: prediction of
      long-term outcome by pretreatment cortisol levels.
AB  - OBJECTIVE: The authors sought to determine whether hypothalamic-pituitary-adrenal
      (HPA) axis activity in patients before their treatment for panic disorder can
      predict follow-up functional status. Although baseline HPA axis disturbances in
      patients with panic disorder appear to attenuate with treatment, there is
      evidence that they may be linked to poorer long-term outcomes. METHOD: Follow-up
      clinical data were obtained for 18 of 20 patients with panic disorder who
      participated in a detailed study of HPA axis activity in panic, both before and
      during their treatment with alprazolam. HPA axis assessment included monitoring
      of adrenocorticotropin and cortisol over a full circadian cycle. The
      relationships between disability and clinical status at 2-year follow-up and HPA
      axis overactivity at entry were examined. RESULTS: Mean 24-hour cortisol levels
      before treatment provided a strong, positive predictor of disability scores at
      follow-up. Those patients who achieved the treatment goal of medication-free
      remissions had less evidence of HPA axis overactivity at entry than those who
      were not in remission. CONCLUSIONS: HPA axis activity before treatment did
      predict outcome 2 years later. This relationship appears robust and reproducible.
      Further work is needed to define the neuroendocrine mechanisms underlying the HPA
      axis markers that are linked to long-term functioning and to determine the
      biological, psychological, and social processes that link HPA axis disturbance to
      poorer outcomes.

PMID- 8540596
TI  - Money matters: a meta-analytic review of the effects of financial incentives on
      recovery after closed-head injury.
AB  - OBJECTIVE: The authors evaluated the impact of financial incentives on
      disability, symptoms, and objective findings after closed-head injury. METHOD:
      Meta-analysis was used to review the literature. Seventeen reports, covering 18
      study groups and a total of 2,353 subjects, contained data from which effect
      sizes could be calculated. Effect sizes were aggregated after weighting for group
      size. After discussion, there was 100% agreement between the authors on all
      calculations. RESULTS: A moderate overall effect size, 0.47, was found. The
      effect was particularly strong for mild head trauma. The data showed more
      abnormality and disability in patients with financial incentives despite less
      severe injuries. CONCLUSIONS: Clinical evaluation of patients after closed-head
      injury, particularly mild head trauma, must include consideration of the effect
      of financial incentives on symptoms and disability.

PMID- 8540597
TI  - Anorexia nervosa and bulimia nervosa in alcohol-dependent men and women and their
      relatives.
AB  - OBJECTIVE: Many of the studies linking anorexia nervosa and bulimia nervosa to
      substance use disorders suffer from problems with small samples; some lack
      rigorous definitions of the syndromes, and it is difficult to determine whether
      eating problems were primarily temporary consequences of heavy substance use or
      drugs were temporarily used in an effort to control appetite. The goal of this
      study was to evaluate the relationship between alcohol dependence and eating
      disorders. METHOD: Structured interviews were carried out with 2,283 women and
      1,982 men as part of the Collaborative Study on the Genetics of Alcoholism. Data
      on drug abuse and dependence, psychiatric disorders, and symptoms of anorexia and
      bulimia were evaluated among alcohol-dependent probands, their relatives,
      comparison probands, and their relatives. RESULTS: Lifetime rates for anorexia
      and bulimia were 1.41% and 6.17%, respectively, for the alcohol-dependent women,
      and bulimia was observed in 1.35% of the alcoholic men. However, once the impact
      of additional primary diagnoses was controlled for, anorexia was seen in only
      1.26% of the women with primary alcohol dependence and none of the alcohol
      dependent men; the rates for bulimia were 3.46% and 0.72%, respectively. There
      was no evidence of a strong familial crossover between alcohol dependence and
      anorexia or bulimia. CONCLUSIONS: While the rate of anorexia was not elevated in
      alcoholics after controlling for other disorders, bulimia did occur at a greater
      than expected rate. However, both eating disorders were relatively rare, and much
      of the association with alcoholism occurred in the context of additional
      preexisting or secondary psychiatric disorders.

PMID- 8540598
TI  - Serotonergic and noradrenergic dysregulation in alcoholism: m
      chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics
      and healthy comparison subjects.
AB  - OBJECTIVE: This study compared serotonergic (5-HT) and noradrenergic reactivity
      in recently detoxified alcoholic patients and healthy comparison subjects.
      METHOD: Participants were 22 male inpatients who met DSM-III-R criteria for
      alcohol dependence and who were abstinent for 12-26 days and 13 male healthy
      comparison subjects. Subjects completed 3 days of testing over 2 weeks under
      double-blind conditions that involved the intravenous infusions of m
      chlorophenylpiperazine (mCPP), yohimbine, or a saline placebo. Drug effects on
      mood, physiologic responses, and plasma levels of cortisol, prolactin, and 3
      methoxy-4-hydroxyphenylglycol (MHPG) were measured. RESULTS: Both mCPP and
      yohimbine infusion increased nervousness, vital signs, and plasma cortisol,
      prolactin, and MHPG levels relative to placebo Cortisol responses to mCPP were
      blunted in the alcoholic patients relative to the comparison subjects. Cortisol
      and prolactin responses to yohimbine were greater in the alcoholic patients,
      whereas their pulse increases after yohimbine infusion were blunted. No group
      differences emerged in MHPG, nervousness, or blood pressure responses to either
      drug. CONCLUSIONS: This study documents persistent alterations in neuroendocrine
      responsivity of both 5-HT and noradrenergic systems in alcoholic patients after
      detoxification. Blunted cortisol responses to mCPP in these recently detoxified
      patients may reflect reductions in 5-HT2 receptor function. The absence of
      altered MHPG responses to yohimbine in the alcoholic patients suggests that
      presynaptic noradrenergic responsivity is not persistently altered in these
      patients. In contrast, the enhanced cortisol responses and reduced pulse
      responses to yohimbine in alcoholic patients may reflect down-regulation of
      postsynaptic noradrenergic receptors.

PMID- 8540599
TI  - Pituitary-adrenal-system regulation and psychopathology during amitriptyline
      treatment in elderly depressed patients and normal comparison subjects.
AB  - OBJECTIVE: This study was done to compare the effects of 6-week treatment with
      amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) regulation in
      elderly depressed patients and age-matched comparison subjects. METHOD: A
      combined dexamethasone-suppression/CRH-stimulation (dexamethasone/CRH) test was
      administered before initiation of amitriptyline treatment and at the end of weeks
      1, 3, and 6 of treatment. Thirty-nine depressed inpatients, mean age = 69 years,
      completed the study. Fourteen normal volunteers, mean age = 67 years, served as
      comparison subjects. RESULTS: In relation to the comparison subjects, the
      depressed patients had a profoundly abnormal HPA response, in particular an
      exaggerated cortisol release in the dexamethasone/CRH test. This abnormality
      began to disappear after 1 week of treatment with amitriptyline. In contrast,
      amitriptyline did not affect neuroendocrine regulation in the comparison subjects
      at any time during the test period. CONCLUSIONS: The data suggest that
      amitriptyline affects HPA regulation in hypercortisolemic depression only, and
      they raise the possibility that normalization of its feedback control is related
      to the antidepressive effect of amitriptyline.

PMID- 8540600
TI  - Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus.
      A clinicopathologic study of 55 cases.
AB  - We present the clinicopathological and immunohistochemical features of 55
      atypical polypoid adenomyofibromas, a definitional expansion of an entity
      previously reported as "atypical polypoid adenomyoma" (APA) of the uterus.
      Patients ranged in age from 25 to 73 (mean, 39.9) years. All but two of the
      patients were premenopausal, and 14 were undergoing evaluation for infertility.
      Histologically, the lesions featured a biphasic proliferation of architecturally
      complex and cytologically atypical endometrial glands within a myofibromatous
      stroma. The histologic pattern ranged from widely separated and loosely clustered
      irregular but branched glands embedded in broad zones of cellular myofibromatous
      stroma to those possessing crowded, markedly complex, branching glands separated
      by sparse intersecting fascicles of fibromuscular tissue. The stroma in all cases
      was actin or desmin positive or both. Morular/squamous metaplasia was present in
      all but two cases and florid in most. All cases exhibited architecturally complex
      glands, and in 25 cases the architectural complexity was indistinguishable from
      that of well-differentiated endometrial adenocarcinoma, as we have defined it;
      that is, they had a high architectural index. Twenty-nine patients were initially
      treated with polypectomy or curettage followed by hormonal therapy; persistent or
      recurrent APA developed in 45% of the patients in this group (33% with low
      architectural index vs. 60% with high architectural index). Five patients had
      successful pregnancies despite persistent disease. Superficial myoinvasion was
      identified in the hysterectomy specimen in two of 12 APAs with a high
      architectural index but not in 21 APAs with a low architectural index. All
      patients are alive and well 1 to 112 months after diagnosis (mean, 25.2 months).
      On the basis of this study, we propose that APAs with markedly complex glands
      (high architectural index) be designated "atypical polypoid adenomyofibromas of
      low malignant potential" (APA-LMP) to emphasize the potential risk for myometrial
      invasion. A treatment program featuring local excision accompanied by close
      follow-up is warranted for APA despite the presence of recurrent or persistent
      disease. Patients with APA-LMP may also, in selected cases, be managed with less
      than hysterectomy, although (as with the usual well-differentiated carcinoma)
      there is a small but definite risk associated with this approach.

PMID- 8540601
TI  - Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural
      Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology.
AB  - A workshop jointly sponsored by the University of Hong Kong and the Society for
      Hematopathology explored the definition, differential diagnosis, and epidemiology
      of angiocentric lymphomas presenting in the nose and other extranodal sites. The
      participants concluded that nasal T/natural killer (NK) cell lymphoma is a
      distinct clinicopathologic entity highly associated with Epstein-Barr virus
      (EBV). In situ hybridization for EBV an be very valuable in early diagnosis,
      especially if tissue is sparse. The cytologic spectrum is broad, ranging from
      small or medium-sized cells to large transformed cells. Histologic progression
      often occurs with time. Necrosis is nearly always present, and angioinvasion by
      tumor cells is seen in most cases. Nasal T/NK cell lymphoma has a characteristic
      immunophenotype: CD2-positive, CD56-positive, but usually negative for surface
      CD3. Cytoplasmic CD3 can be detected in paraffin sections. Clonal T-cell receptor
      gene rearrangement is not found. Tumors with an identical phenotype and genotype
      occur in other extranodal sites, most commonly in the skin, subcutis, and
      gastrointestinal tract, and should be referred to as nasal-type T/NK cell
      lymphomas. The differential diagnosis includes lymphomatoid granulomatosis,
      blastic or monomorphic NK cell lymphoma/leukemia, CD56-positive peripheral T-cell
      lymphoma, and enteropathy-associated T-cell lymphoma.

PMID- 8540602
TI  - Intracranial desmoplastic small-cell tumor. Report of a case.
AB  - We report a case of desmoplastic small-cell tumor occurring in the CNS in
      relation to the tentorium in a 24-year-old man. Morphologically, the neoplasm had
      the typical appearance of small, round tumor cells of primitive appearance
      growing as well-defined nests separated by abundant desmoplastic stroma. The
      diagnosis was confirmed through the demonstration of immunoreactivity for
      keratin, desmin, and neuron-specific enolase and the detection by Southern blot
      analysis of a unique gene resulting from the fusion of the WT1 gene in chromosome
      11 and the EWS gene in chromosome 22. This is the first documented instance of
      the occurrence of this tumor type at a distance from a mesothelial-lined surface.

PMID- 8540603
TI  - A unique dysembryonic neoplasm of the adrenal gland composed of nephrogenic rests
      in a child.
AB  - A primary neoplasm of the right adrenal gland in a 4-year-old boy was discovered
      after the patient developed bowel obstruction following an appendectomy. Until
      the histologic examination, the tumor was thought to be a neuroblastoma. However,
      the intra-adrenal tumor was composed of blastematous nodules, primitive tubules,
      and glomeruloid structures whose overall composition resembled a Wilms' tumor.
      Other than a single focus of mucinous glands, the tumor lacked the range of
      somatic tissue types of a teratoma. Approximately 50 cases of putative extrarenal
      Wilms' tumor have been reported. The retroperitoneum is one of the more common
      primary sites, yet our case is the first documented example of a neoplasm with
      features of a Wilms' tumor arising in the adrenal. Based on the embryologic and
      anatomic relationship between the adrenal gland and kidney, it is somewhat
      surprising that other instances of similar appearing tumors have not been
      described before the present case. Our patient was managed on a Wilms' tumor
      protocol and remains tumor free 15 months after surgery.

PMID- 8540604
TI  - Papillary transitional cell carcinoma.

PMID- 8540605
TI  - Pleomorphic hyalinizing angiectatic tumor of soft parts. A low-grade neoplasm
      resembling neurilemoma.
AB  - Fourteen examples of an unusual mesenchymal tumor characterized by sheets and
      fascicles of mitotically inactive, hemosiderin-stippled, spindled, and
      pleomorphic cells, situated around an angiectatic vasculature, are described. The
      14 tumours developed in eight women and six men (aged 32-83 years) and ranged in
      size from 2.3 to 8 cm. Eleven cases presented in the subcutaneous tissues, of
      which eight were located in the lower extremity. All featured prominent clusters
      of thin-walled ectatic vessels surrounded by perivascular hyaline material
      representing a combination of fibrin and collagen. In three cases the
      perivascular hyalinization was so extensive that it constituted more than half of
      the total tumor area. The tumor cells were similar to those of malignant fibrous
      hystiocytoma but differed from them by the presence of prominent intranuclear
      cytoplasmic inclusions, the extreme scarcity of mitotic figures, and the
      occasional presence of CD-34 expression. These tumors also shared several
      features with neurilemomas, such as their unusual vasculature, intranuclear
      cytoplasmic inclusions, lack of mitotic figures, and abundance of mast cells.
      They could be distinguished from neurilemomas, however, by the usual presence of
      infiltrative margins and the absence of S-100 protein. Follow-up information on
      eight patients (6 months to 25 years) indicated recurrences in four cases, with
      one of the three patients experiencing numerous recurrences over a 25-year
      period. No patient has developed metastases, however. We suggest that this tumor
      is a low-grade sarcoma of uncertain lineage in which the vascular changes are, in
      part, reflective of its slow growth.

PMID- 8540606
TI  - Borderline papillary serous tumour of the fallopian tube.
AB  - We report a case of borderline papillary serous tumor of the fallopian tube in a
      31-year-old woman. The tumor was characterized by the formation of papillary
      projections with focally prominent epithelial stratification and atypia. The
      histologic features of the tumor were largely similar to a borderline serous
      tumor of the ovary. Two years after initial presentation, the patient underwent
      in vitro fertilization and carried the ensuing pregnancy to term. There is no
      evidence of disease nearly 6 years after presentation, which suggests that these
      extremely uncommon tumors can be managed conservatively.

PMID- 8540607
TI  - Biphasic synovial sarcomas arising in the pleural cavity. A clinicopathologic
      study of five cases.
AB  - Five cases of primary synovial sarcoma of the pleura are presented with a
      discussion of differentiation from other biphasic malignant neoplasms, most
      notably malignant mesothelioma. The cases have clinical, histologic, and
      immunohistochemical features consistent with synovial sarcoma of soft tissue. The
      average age at initial presentation of the reported patients was 25 years with an
      approximate range of 9 to 50 years. A large pleural-based intrathoracic mass was
      identified in each case. Histologic analysis showed a biphasic (mixed) pattern
      composed of epithelial and spindle cells. The epithelial cells showed cleft-like
      to tubulopapillary growth with focal intraluminal periodic acid Schiff's (PAS)
      positive, diastase-resistant secretions identified in four of the five cases. The
      spindle cell component was composed predominantly of densely packed, elongated,
      fusiform cells. Immunohistochemical staining showed positivity with antibodies
      against cytokeratin, BER.EP4, epithelial membrane antigen, and vimentin in all
      cases. The patients seem to have an aggressive course, with four deaths reported
      within 3 years from initial surgery. These cases represent the first reported
      cases of primary synovial sarcoma of the pleura and lend further credence to the
      theory that synovial sarcomas are derived from immature mesenchymal elements, not
      from synovium.

PMID- 8540608
TI  - Tubular adenosis of the breast. A distinctive benign lesion mimicking invasive
      carcinoma.
AB  - Tubular adenosis, a term first coined by Oberman, is an uncommon benign lesion of
      the breast that may mimic invasive carcinoma. There is no formal description of
      this condition in the literature. We report the findings on six specimens from
      five patients (one with bilateral disease), including three that showed
      cancerization by intraductal carcinoma (DCIS). The ages of the patients ranged
      from 40 to 82 years. One patient presented with a 3-cm breast mass, and the
      others were found in specimens resected for infiltrating ductal carcinoma (two
      specimens) or DCIS (three specimens). The histologic hallmark of tubular adenosis
      was haphazard proliferation of elongated tubules that were noncrowded, narrow,
      and sometimes branching. There was no lobular arrangement or, at most, vague
      lobular grouping, with some tubules often extending into the fat. The tubules
      contained basophilic or granular eosinophilic secretion. The stroma was sclerotic
      to edematous. The tubules were lined by bland-looking ductal cells and were
      surrounded by an intact myoepithelial layer, a phenomenon well highlighted by
      immunostaining for muscle-specific actin (HHF-35) or S-100 protein. In three
      specimens, the tubular adenosis was cancerized by noncomedo DCIS, producing a
      pattern strongly mimicking infiltrating carcinoma; the in situ nature of the
      carcinoma was confirmed by actin immunoreactivity in the residual myoepithelium
      as well as by the presence of architecturally similar tubular adenosis in the
      vicinity. Tubular adenosis shows an infiltrative growth similar to microglandular
      adenosis and adenomyoepithelial adenosis, but it differs from them by the
      interdigitating tubular configuration and also differs from microglandular
      adenosis by the presence of myoepithelium. Tubular adenosis can be distinguished
      from sclerosing adenosis by the lack of obvious lobular architecture or whorled
      arrangement and wider separation of the tubules. Tubular adenosis appears to be a
      benign lesion per se, but whether it has premalignant potential remains to be
      determined. The importance of recognizing this entity lies in its being
      potentially mistaken for invasive carcinoma, especially at intraoperative frozen
      section or when the lesion is cancerized by DCIS.

PMID- 8540609
TI  - Granular cell change in astrocytic tumors.
AB  - Intracerebral granular cell neoplasms are uncommon. We report five hemispheric
      astrocytomas, all of which showed the distinctive features of granular cell
      change, being composed exclusively or predominantly of rounded cells with coarse
      granular eosinophilic cytoplasm and eccentrically placed nuclei. Four showed
      clear foci of transition from an anaplastic astrocytoma and contained lipidized
      as well as granular cells. In all tumors, the cytoplasmic granules were positive
      for periodic acid Schiff and resistant to diastase digestion, and there was focal
      glial fibrillary acidic protein expression. In addition, diffuse cytoplasmic
      positivity with epithelial membrane antigen antiserum was present, but in no case
      was there true membrane staining. Ultrastructural appearances were similar in
      four cases, showing the cytoplasm of tumor cells to be filled with membrane-bound
      autophagic vacuoles; bundles of intermediate filaments were also seen in some
      cells. Despite earlier controversy over the histogenesis of granular cell tumors,
      it is now clear that granular change is a degenerative phenomenon that, like
      lipidization, can occur in tumors of different cell types, including--rarely-
      astrocytic neoplasms. It is important that this histologic variant be recognized,
      as on a small biopsy sample diagnostic confusion with an infarct, demyelinating
      disease or a secondary carcinoma is a real possibility.

PMID- 8540610
TI  - Lymphoid monoclonal antibodies reactive with lung tumors. Diagnostic
      applications.
AB  - In the course of investigating 30 monoclonal antibodies (MAbs) for their
      potential reactivity with 25 lung tumors of different histologic types, we found
      that three MAbs commonly used for their specificities for lymphoid markers were
      highly reactive with non-small-cell carcinomas (NSCLC) and totally nonreactive
      with small-cell carcinomas (SCLC). Immunostaining was performed by the standard
      streptavidin-biotin-peroxidase method after microwave antigen retrieval on
      formalin-fixed, paraffin-embedded tissue sections. LN2 (CD74), LN3 (HLA-DR), and
      BLA-36, which are commonly used for the identification of B-lymphocytes, strongly
      immunostained 19 of 25 squamous and adenocarcinomas and none of 34 small-cell
      carcinomas and carcinoids. Moreover, in combined tumors, these MAbs selectively
      stained the adenocarcinoma cells but not the adjacent small-cell carcinoma cells.
      A cocktail mixture of LN2, LN3, and BLA-36 assayed on 24 additional lung tumors
      produced similar results with even stronger and sharper stainings. Other lymphoid
      MAbs showed some selective staining but to a lesser degree. Among nonlymphoid
      MAbs, the results were as expected, with MAbs for cytokeratin (B72.3) and
      epithelial membrane antigen staining NSCLC but also some SCLC. The MAbs for
      chromogranin and neuron-specific enolase were not entirely specific, whereas some
      nerve-cell adhesion molecule MAbs showed good specificity for SCLC. In a field
      with few specific MAbs, the newly discovered ability of these lymphoid MAbs to
      discriminate between SCLC and NSCLC may prove useful in the immunohistochemical
      diagnosis of lung tumors.

PMID- 8540611
TI  - Juvenile granulosa cell tumor of the infantile testis. Evidence of a dual
      epithelial-smooth muscle differentiation.
AB  - We report the ultrastructure and immunohistochemical profile of seven juvenile
      granulosa cell tumors of the infantile testis. The infants' ages ranged from 1
      day to 11 months. All tumors had characteristics ultrastructure with a mixture of
      spindle smooth-muscle and theca cells and polygonal granulosa cells. Clusters of
      polygonal granulosa cells were invested by a continuous basal lamina and
      contained bundles of distinct cytoplasmic filaments with evenly distributed dense
      bodies resembling smooth muscle. These filaments were occasionally attached to
      well-developed, prominent desmosomes. Tumor cells had a conspicuous rough
      endoplasmic reticulum and Golgi complex and occasional neutral fat droplets. In
      all tumors, mitochondria had laminated cristae and only rarely were there cristae
      with a tubulovesicular pattern characteristic of steroid secreting cells. Tumor
      cells stained focally with low-molecular-weight cytokeratins (8,18, and 19),
      smooth-muscle-specific actin, desmin, and more noticeably with vimentin. These
      ultrastructural and immunohistochemical features of dual epithelial-mesenchymal
      differentiation and distinct muscle-like filaments with dense bodies are
      characteristic of the juvenile granulosa cell tumor of the infantile testis.

PMID- 8540612
TI  - Divergent differentiation in pleomorphic xanthoastrocytoma. Evidence for a
      neuronal element and possible relationship to ganglion cell tumors.
AB  - We report the detection of cytoplasmic immunoreactivity for
      neuronal/neuroendocrine antigens in a subpopulation of tumor cells within seven
      pleomorphic xanthoastrocytomas (PXAs). The expression of glial and neuronal
      polypeptides was examined in routinely prepared surgical resections by
      immunohistochemistry using well-characterized antibodies that recognize glial
      fibrillary acidic protein (GFAP), synaptophysin (SYN), and neurofilament triplet
      polypeptides (NFPs) in microwave-enhanced single- and double-immunolabelling
      experiments. Each neoplasm contained cells that were immunoreactive for SYN
      and/or NFPs, GFAP, and occasionally for both GFAP and either NFP or SYN. We
      conclude that abortive neuronal/neuroendocrine differentiation may occur in PXAs,
      suggesting a relationship between PXA and other developmental neoplasms that
      reveal a more overt neuronal phenotype, such as ganglioglioma, dysembryoplastic
      neuroepithelial tumor, and desmoplastic ganglioglioma, and with tumors expressing
      ambiguous glial/neuronal lineage, such as the subependymal giant cell tumor of
      tuberous sclerosis. These findings suggest that aberrant expression and
      accumulation of neuronal intermediate filaments may account for the large,
      pleomorphic cell morphology observed in many of these tumors.

PMID- 8540613
TI  - Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal
      prostate and prostatic carcinoma. A randomized study.
AB  - The morphologic changes induced by neoadjuvant combination endocrine therapy were
      evaluated in prostatectomy specimens from patients diagnosed with localized
      prostate cancer. These patients participated in a prospective, randomized
      clinical trial investigating the effect of 3 months of combination therapy with
      flutamide and an LHRH agonist prior to radical prostatectomy versus radical
      prostatectomy alone. Ninety-six radical prostatectomy specimens processed
      according to the same protocol were evaluated without knowledge of prior
      treatment. Forty-seven patients were randomly assigned to the neoadjuvant
      combination therapy group and 49 to the control arm. Compared with the control
      group, several changes were strongly and significantly associated with exposure
      to neoadjuvant combination therapy. The nonmalignant prostatic tissue showed
      strong prominence and hyperplasia of the basal cell layer, accompanied by
      epithelial cell vacuolization and markedly reduced occurrence of prostatic
      intraepithelial neoplasia (p < 0.001) after combination therapy. Prostate cancer
      tissue, on the other hand, showed smaller nucleoli (p < 0.001), cell
      vacuolization (p < 0.001), rare intraluminal crystalloids (p < 0.001), higher
      Gleason grade (p < 0.001), lower prevalence of capsular penetration (p < 0.001),
      and less frequent invasion of the perineural spaces (p < 0.001) and surgical
      margins (p = 0.002). Tumor volume, was also reduced by more than 40% in the
      treated group (p = 0.007). The present findings show that preoperative endocrine
      combination therapy induces highly characteristic changes in both nonmalignant
      and cancerous prostatic tissue. Furthermore, following endocrine treatment, the
      surgical margins are less likely to be involved by cancer and capsular
      penetration is reduced.

PMID- 8540614
TI  - Diverticular disease-associated chronic colitis.
AB  - A clinical syndrome of chronic colitis unique to the sigmoid colon harboring
      diverticular was recently reported; its histopathological appearance has not been
      fully elucidated. In this study, the authors analyzed the clinical and
      pathological features of 23 patients (age range, 38-87 years; median age, 72
      years) with diverticular disease-associated chronic colitis. Nineteen presented
      with hematochezia; four had abdominal pain. Colonoscopic visualization of the
      mucosa showed patchy or confluent granularity and friability affecting the
      sigmoid colon encompassing diverticular ostia. Colonic mucosae proximal and
      distal to the sigmoid were endoscopically normal. Mucosal biopsy specimens showed
      features of idiopathic inflammatory bowel disease that included plasmacellular
      and eosinophilic expansion of the lamina propria (100%), neutrophilic cryptitis
      (100%) with crypt abscesses (61%), basal lymphoid aggregates (100%), distorted
      crypt architecture (87%), basal plasmacytosis (61%), surface epithelial sloughing
      (61%), focal Paneth cell metaplasia (48%), and granulomatous cryptitis (26%).
      Concomitant rectal biopsies obtained in five patients demonstrated histologically
      normal mucosa. Fourteen patients treated with high-fiber diet or antibiotics or
      both improved clinically, as did nine patients administered sulfasalazine or 5
      aminosalicylic acid. Five patients underwent sigmoid colonic resection, three for
      stricture with obstruction and two for chronic blood loss anemia. Among a control
      population of 23 age- and gender-matched patients with diverticular disease
      without luminal surface mucosal abnormality, none required resection during the
      same follow-up period. By Fisher's exact test, a statistically significant
      difference in outcome for patients with and without colitis was detected (p =
      0.049). In addition, three patients developed ulcerative proctosigmoiditis 6, 9,
      and 17 months after the onset of diverticular disease-associted colitis. The data
      indicate that diverticular disease-associated chronic sigmoid colitis expresses
      morphological features traditionally reserved for idiopathic inflammatory bowel
      disease. Its clinical and endoscopic profiles permit distinction from Crohn's
      disease and ulcerative colitis. Patients with chronic colitis in conjunction with
      diverticula are at increased risk for sigmoid colonic resection. Diverticular
      disease-associated chronic colitis may also precede the onset of conventional
      ulcerative proctosigmoiditis in some cases.

PMID- 8540615
TI  - Simple and rapid method for simultaneous gas chromatographic determination of
      bitertanol, metalaxyl, oxadixyl, propiconazole, and triadimefon residues in
      cucumbers.
AB  - A simple and rapid method for the determination of bitertanol, metalaxyl,
      oxadixyl, propiconazole and triadimefon residues in cucumbers has been developed.
      The fungicide residues were extracted from the sample with ethyl acetate and
      determined, after an automated gel permeation chromatographic clean-up, by GC
      with nitrogen-phosphorus detection. Cucumbers fortified with fungicides in the
      laboratory were analysed using the proposed method and that of Luke, Frooberg,
      Masumoto and Doose (J. Assoc. Off. Anal. Chem., 1981, 64, 1187). For the proposed
      method, mean recoveries ranged from 87.9% for bitertanol to 96.5% for oxadixyl.
      For the method of Luke et al. mean recoveries ranged from 79.8% for triadimefon
      to 97.8% for bitertanol. Cucumbers treated with the fungicides in the field were
      also analysed by these two methods. For the determination of all these five
      fungicides, no difference was observed at the 5% significance level.

PMID- 8540616
TI  - Determination of carbosulfan in oranges by high-performance liquid chromatography
      with post-column fluorescence.
AB  - High-performance liquid chromatography equipped with post-column fluorescence
      derivatization provides an automated and specific analytical method for pesticide
      determination. Carbosulfan, a carbamate pesticide, can be analysed utilizing an
      existing and proven carbamate system after the addition of one additional
      hydrolytic reactor in-line. Extraction of this compound from citris crops
      requires careful handling owing to the volatility and unstable nature of the
      analyte in acid conditions. This paper describes the necessary instrument
      modifications and presents a method for carbosulfan extraction. Analyses of
      orange homogenates were performed rapidly with recoveries of between 66 and 98%
      for residue levels between 0.03 and 0.25 micrograms kg-1.

PMID- 8540617
TI  - Determination of benzoic and sorbic acids in packaged vegetable products.
      Comparative evaluation of methods.
AB  - Three analytical methods for determining sorbic and benzoic acids in various
      packaged vegetable products were evaluated, with special attention being paid to
      green olives. Two of these methods used a simple, isocratic, reversed-phase HPLC
      technique for separating and detecting the preservatives, but differed in the
      preparation of the sample (extraction with 60% methanol or steam distillation).
      The third method was based on separation by steam distillation and determination
      of the acids in the distillate by spectrophotometry. For the olives, while this
      method proved to be excellent (total error < 25%) for high concentrations (> 100
      ppm), the HPLC methods were more efficient for the whole range of concentrations
      studied (5-500 ppm). Both HPLC methods had detection limits of approximately 1
      ppm for the two preservatives. With other sample matrices (tomatoes, cucumbers,
      caperberries, silver-skinned onions and hot peppers), the three methods proved to
      be excellent for high concentrations of preservatives (500 ppm), but at low
      levels (20 ppm), the spectrophotometric method and the HPLC method with
      extraction by 60% methanol proved to be unacceptable (total error > 50%) in some
      cases.

PMID- 8540618
TI  - Determination of vitamins A, E and K1 in milk by high-performance liquid
      chromatography with dual amperometric detection.
AB  - A high-performance liquid chromatographic method with dual-electrochemical
      detection (HPLC-DEC) for the simultaneous determination of vitamins A, E and K1
      is described. Separation was carried out using a C18 reversed-phase column and
      2.5 mmol l-1 acetic acid-sodium acetate in methanol-water (99 + 1, v/v) as the
      mobile phase. The compounds eluted with good resolution in the above mentioned
      order within about 20 min and were quantified by dual-amperometric detection with
      a glassy carbon electrode at -1100 mV (E1) and + 700 mV (E2) (versus Ag/AgCl).
      This reductive-oxidative detection mode gave reproducible results and the
      detection limits were of the order of 0.06, 0.19 and 3.1 ng for vitamins A, E and
      K1, respectively. The HPLC-DEC method was successfully applied to the analysis of
      vitamins A, E and K1 in liquid cows' milk and infant-formula powdered-milk
      samples after applying alkaline hydrolysis of the fatty material and extraction
      of the vitamins with hexane for the analysis of vitamins A and E. In the case of
      vitamin K1 it was necessary to carry out enzymic hydrolysis, since this vitamin
      is degraded in basic medium, followed by cleaning with a Sep-Pak silica cartridge
      to isolate it from the other vitamins. Good recoveries (between 81 and 106%) were
      obtained.

PMID- 8540620
TI  - Determination of sulfadoxine concentrations in whole blood using C18 solid-phase
      extraction, sodium dodecyl sulfate and dimethylaminocinnamaldehyde.
AB  - A simple method is described for the extraction and subsequent analysis of
      sulfadoxine in human whole blood using a solid-phase extraction technique and
      colorimetric reaction. This procedure utilizes the micellar properties of sodium
      dodecyl sulfate to: (1) extract sulfadoxine from a C18 solid-phase sample
      preparation column; (2) enhance the colorimetric reaction produced by the
      addition of p-dimethylaminocinnamaldehyde (DMAC); and (3) provide stability to
      the coloured product generated by the reaction of sulfadoxine with DMAC. The
      intense, violet-red colour reaction can be conveniently used for qualitative and
      semiquantitative visual interpretations of sulfadoxine levels. Under the assay
      conditions, drug concentrations in the blood of subjects receiving sulfadoxine
      were determined from absorbance measurements. These results correlated well with
      the sulfadoxine levels determined from high-performance liquid chromatographic
      analysis. Important advantages of the procedure include the ability to evaluate
      small samples of whole blood (100 microliters), the minimal use of organic
      solvents, no sophisticated instrumentation, and formation of a stable, coloured
      reaction product. The method proved to be a suitable field assay for determining
      whole-blood levels of sulfonamides in the concentration range from 5 to 100
      micrograms ml-1.

PMID- 8540619
TI  - Simultaneous determination of rufloxacin and theophylline by high-performance
      liquid chromatography in human plasma.
AB  - A sensitive, specific and rapid liquid chromatographic procedure to monitor
      rufloxacin and theophylline selectively in human plasma has been developed and
      validated. Plasma samples were extracted with a mixture of dichloromethane
      diethyl ether. The organic layer was evaporated to dryness, reconstituted with
      mobile phase, and the analytes were separated and quantified by LC on an
      octadecylsilane column with acetonitrile-0.1 mol dm-3 phosphate buffer (pH3) as
      mobile phase and UV detection at 280 nm. The procedure was linear from 0.05 to
      5.0 micrograms cm-3, with a detection limit of 0.03 micrograms cm-3 for
      rufloxacin, and from 0.5 to 30 micrograms cm-3, with a detection limit of 0.02
      micrograms cm-3 for theophylline. The accuracy of the method was defined by
      relative errors of 4.2, 5.0 and 1.6% for human plasma containing 0.1, 1.0 and 5.0
      micrograms cm-3 of rufloxacin and 2.4, 2.0 and 2.7% at the concentrations of 1.0,
      5.0 and 20 micrograms cm-3 for theophylline. The corresponding relative standard
      deviations were 3.4, 2.8 and 1.7% for rufloxacin and 2.1, 3.7 and 3.8% for
      theophylline at the same concentrations, respectively. The assay has been
      successfully applied to pharmacology, toxicology and pharmacokinetics studies in
      humans.

PMID- 8540621
TI  - Cadmium, copper and zinc complexes of poly-L-cysteine.
AB  - The metal complexes of poly-L-cysteine (PLC) were evaluated for their potential
      use in trace metal preconcentration and separation. Formation constants (log K)
      for the Cd2+ and Zn2+ complexes of PLC estimated by spectrophotometric titration
      were 8.0 +/- 0.8 and 9.5 +/- 0.5, respectively. The PLC sulfhydryl groups were
      most likely oxidized to disulfides by Cu2+, and binding of Cu+ with the molecule
      was expected. The moles of metal bound by PLC reflecting its strongest sites
      relative to a stable competing ligand for Cu2+ and Zn2+ were 1.4 and 0.40 mmol g
      1 of PLC, respectively. The presence of Na+ (29 mmol l-1) or Ca2+ (0.5 mmol l-1)
      had no measurable effect on the amount of Zn-PLC complex formed.

PMID- 8540622
TI  - Morphology of the dorsal phalangeal connective tissue body.
AB  - BACKGROUND: The connective tissue body of the dorsal finger is partitioned by
      multiple horizontal lamellae derived from expansions of intercellular spaces.
      These connective fibres are involved in providing gliding spaces for the extensor
      apparatus, and they formed spreading rooms of infection processes. METHODS: In
      order to describe the topographical histological and histochemical behavior of
      cellular and intercellular elements of the border lamellae of the dorsal
      aponeurosis of the fingers, a modified method of Epoxid resin embedding technique
      without pre-infiltration is used. RESULTS: The bordering elements of the
      connective tissue lamellae described in this investigation are especially well
      defined in the region of the dorsal aponeurosis. The morphological examinations
      show that both the expansions of the intercellular space as well as defined
      fibrocytic cellular elements function in a manner equivalent to a synovial
      membrane of tendon sheaths. CONCLUSIONS: Saving or reconstructing these
      structures appears to be of importance in preventing for adhesive disorders of
      finger motion following surgical intervention in this region.

PMID- 8540623
TI  - Distribution and colocalization of NADPH-diaphorase activity, nitric oxide
      synthase immunoreactivity, and VIP immunoreactivity in the newly hatched chicken
      gut.
AB  - BACKGROUND: The distribution and colocalization of nitric oxide synthase and
      NADPH-diaphorase have been investigated quite extensively in the mammalian gut;
      however, no such study has been undertaken in the avian gut. In the present
      report, we have therefore studied the distribution and coexpression of nitric
      oxide synthase (NOS), NADPH-diaphorase, and vasoactive intestinal polypeptide
      (VIP) in enteric neurons of the newly hatched chicken gut. METHODS:
      Immunohistochemical methods were used to detect NOS immunoreactivity (NOS-IR) and
      VIP immunoreactivity (VIP-IR). NADPH-diaphorase activity was detected using a
      histochemical technique. RESULTS: Neurons expressing NADPH-diaphorase activity,
      NOS-IR, and VIP-IR were detected in both the myenteric and submucous plexus of
      all regions of the gastrointestinal tract examined. All NADPH-diaphorase positive
      neurons were also NOS-IR and all NOS-IR neurons were NADPH-diaphorase positive,
      in both plexuses, indicating that NADPH-diaphorase can be used as a marker for
      NOS containing neurons in the chicken gut. The majority of VIP-IR neurons also
      expressed NADPH-diaphorase activity. Only few neurons that expressed NADPH
      diaphorase activity did not express VIP-IR. The proportion of VIP immunopositive
      neurons that were NADPH-diaphorase negative increased anally and these neurons
      were more prominent in the submucous than the myenteric plexus ganglia. NADPH
      diaphorase positive, NOS-IR, and VIP-IR nerve fibres were detected in the
      circular muscle, but very few, if any, were present in the longitudinal muscle.
      VIP-IR, but not NOS-IR or NADPH-diaphorase activity, was detected in mucosal
      fibres, in contrast to the situation in the mammalian gut. CONCLUSIONS: These
      results indicate that in birds, as in mammals, nitric oxide may play a role in
      the neural control of the gut musculature, but that it is unlikely to be involved
      in the nervous control of mucosal activity.

PMID- 8540624
TI  - Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid
      treatment.
AB  - BACKGROUND: In a recently developed chick model the teratogen retinoic acid has
      appeared to induce a spectrum of double outlet right ventricle, which needs
      further detailed evaluation. It is known that retinoic acid is able to induce
      cardiac malformations. Although the exact mechanism is not known, an interaction
      with neural crest cell function is thought to exist. METHODS: After treatment
      with 1 microgram all-trans retinoic acid at Hamburger and Hamilton stage 15 and
      reincubation until stage 34 of development 41 chicken embryos were evaluated
      macroscopically and microscopically, supported by graphic reconstructions. These
      retinoic acid treated embryos were compared with a control group (n = 8).
      RESULTS: The retinoic acid treated embryos could be divided in three groups.
      Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular
      septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle
      (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal
      course of the subaortic outflow tract. In the group with DORV a straddling
      tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be
      distinguished. Considering the external contour, the hearts in the DORV group all
      showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found
      in all three groups (11/41) and with a great diversity. CONCLUSIONS: The present
      cardiac malformations in the chicken as a result of retinoic acid treatment are
      part of a continuous spectrum, varying from hearts with an intact ventricular
      septum and a normal course of the subaortic outflow tract to a double outlet
      right ventricle with a straddling tricuspid orifice or even a double inlet left
      ventricle. A remarkable observation in this spectrum concerns the correlation of
      malformations of the inflow and outflow tracts, which is explained as a cardiac
      looping disturbance. The disturbance of the looping process seems to lead to
      malalignment of septal components, although, in the chick, retinoic acid does not
      in general interfere with the formation of these septal components themselves.

PMID- 8540625
TI  - Immunocytochemical localization of the protein reactive to human beta-1, 4
      galactosyltransferase antibodies during chick embryonic skin differentiation.
AB  - BACKGROUND: beta-1, 4-Galactosyltransferase (GalTase) transfers galactose from
      UDP-galactose to terminal N-acetylglucosamine in glycoconjugates and is located
      both in the Golgi apparatus and in the plasma membrane. The cell surface GalTase
      is thought to be involved in cell-to-cell recognition and cell-to-extracellular
      matrix interaction. METHODS: By the use of specific monoclonal antibodies against
      human GalTase, changes in cell surface localization of the protein reactive to
      the antibodies in chick embryonic skin during its differentiation in vivo and in
      vitro were detected immunohistochemically at both light- and electron microscopic
      levels. The distribution of glycoconjugates having terminal N-acetylglucosamine
      residues was detected by staining with succinylated wheat germ agglutinin (s
      WGA). RESULTS: Under the light microscope, intense immunostaining was observed in
      the keratinized epidermis, particularly in the intermediate layer. Marked changes
      in the localization of the staining were observed in vitamin A-induced mucus
      secreting skin, in which keratinization was suppressed. The localization of the
      immunostaining was in parallel with that of glycoconjugates having terminal N
      acetylglucosamine residues. Immunoelectron microscopically the immunostaining was
      located on the cell surface and in the intercellular space of the desmosomes in
      the intermediate cells of the keratinized epidermis. However, the staining was
      not present on the cell surface but was detected on the limiting membrane of the
      mucous granules, in the mucous metaplastic epidermis. In contrast, the staining
      was always found in the Golgi apparatus in all of the cells. CONCLUSIONS: These
      results suggest that the protein reactive to human GalTase antibody may be
      involved in chick epidermal differentiation.

PMID- 8540626
TI  - Development and degeneration of the arterial system in the mesonephros and
      metanephros of chicken embryos.
AB  - BACKGROUND: The general morphology of the mesonephric and metanephric arteries in
      chicken embryos has already been described previously. Moreover, the general
      basis of glomerulogenesis has also been established. However, the degeneration of
      the mesonephric vascular system, and especially glomerular degeneration, have not
      been well established yet. Also the morphology of the metanephric angiogenic buds
      has not been studied yet. METHODS: Scanning electron microscopy of vascular
      corrosion casts and critical point dried specimens as well as light microscopy of
      serially sectioned material has been used in this study. Mesonephric degeneration
      coincides in time with metanephros growth and maturation in the developmental
      stages of chicken embryos chosen for this investigation (7.5, 9, 11, and 14 days
      of incubation). RESULTS: The arterial system of the mesonephros in embryonic
      chicken is similar to that of the anuran kidney, as described in the literature.
      The morphology of the degenerating mesonephric glomeruli shows that the
      glomerular capillaries are more thick, tortuous, and numerous than those in
      normal glomeruli. The podocytes also show degeneration. The arterial system of
      the metanephros grows directly from the aorta and from the mesonephric arterial
      system. During these stages of rapid growth, the metanephros shows angiogenic
      buds. These angiogenic buds can be either pointed or round blind endings.
      CONCLUSIONS: The distribution and topography of the mesonephric and metanephric
      arteries is in general accordance with the literature. The process of glomerular
      degeneration in the mesonephros seems similar to glomerular senescence in man but
      is different from that of the aged rat glomeruli. The round angiogenic buds
      observed in the metanephros resemble tumoral angiogenic buds in some aspects.
      However, both angiogenesis and the degenerative phenomena are part of the normal
      developmental process. Consequently, the involved mechanisms are probably under
      sole genetic control. The system studied here offers therefore the possibility to
      study vascular growth and degeneration on the same model in physiological
      conditions without application of vasoactive or pathological agents.

PMID- 8540627
TI  - Age-induced hypertrophy of astrocytes in rat supraoptic nucleus: a cytological,
      morphometric, and immunocytochemical study.
AB  - BACKGROUND: In the adult rat, neuron-astroglia interactions in the supraoptic
      nucleus (SON) are characterized by the structural and functional plasticity of
      astrocytes in response to several physiological and experimental conditions. This
      study has analyzed the plasticity of the supraoptic nucleus astrocytes in
      response to the age-induced changes in neuronal activity. METHODS: The study was
      performed in 5-, 12-, 18- and 24-month-old rats. The cytology and organization of
      astrocytes in the SON were examined using glial fibrillary acidic and vimentin
      immunocytochemistry and ultrastructural and morphometric analysis. RESULTS: No
      significant age-related variations in the total number of neurons and astrocytes
      in the SON were detected, although a few degenerating neurons were found in old
      rats. An age-dependent increase in GFAP immunoreactivity was observed at the
      ventral glial lamina, perivascularly and between neuronal perikarya. Vimentin
      overexpression was also detected in ventral lamina astrocytes with advancing age.
      At the cell nucleus level, we observed an age-associated increase in nuclear size
      and in the number of coiled bodies, nuclear bodies, and "cleared" nucleoplasmic
      areas, as well as changes in the nucleolar organization. At the cytoplasmic
      level, characteristic ultrastructural features in astrocytes of old rats were the
      hypertrophy of intermediate filament bundles and the formation of an extensive
      network of Golgi stacks interlinked by tubulovesicular elements. Glial filaments
      were often associated with the nuclear envelope and polyribosomes. CONCLUSIONS:
      The increased GFAP and vimentin immunoreactivity and the morphometric and
      cytological changes in rat SON astrocytes may reflect a sustained upregulation of
      cellular activity with age, resulting in hypertrophy of glial perikarya and cell
      processes. Several factors that are known to influence the expression of the
      astrocytic phenotype, such as signals produced by degenerating neurons and
      activated microglia, as well as variations in neuronal activity are considered
      possible causes of the age-associated changes in SON astrocytes.

PMID- 8540628
TI  - Gemelli and obturator internus muscles: different heads of one muscle?
AB  - BACKGROUND: The superior gemellus, inferior gemellus, and obturator internus
      muscles were once regarded as a single muscle judging from their insertion and
      function. However, current textbooks of anatomy do not treat them as one muscle.
      In gross anatomy, the classification of muscles depends largely upon the nerve
      supply, so that the present author re-examined the nerve supply to the three
      muscles. METHODS: Fourteen nerve-muscle specimens were taken from 12 cadavers
      (five males and seven females) and examined with the unaided eye and under a
      dissecting microscope. RESULTS: (1) The modes of nerve supply to the superior
      gemellus, inferior gemellus, and obturator internus muscles differed; however,
      the nerves to the muscles shared the same spinal nerve components. (2) The
      gemelli formed a muscular pocket ("gemellus pocket") through which obturator
      internus muscle passed. CONCLUSIONS: In light of this knowledge on nerve muscle
      relationships, the difference in the pattern of nerve supply to the superior
      gemellus, inferior gemellus, and obturator internus muscles cannot be the basis
      for stating that the muscle are independent. Rather, their fusion to form the
      gemellus pocket and their common insertion suggest that they are different heads
      of one muscle.

PMID- 8540629
TI  - Three-dimensional (3D-) reconstruction of M cells in rabbit Peyer's patches:
      definition of the intraepithelial compartment of the follicle-associated
      epithelium.
AB  - One of the major cell components of the rabbit follicle-associated epithelium is
      represented by the M cells. M cells are able to harbour variable amounts of
      immunocompetent cells inside peculiar invaginations of their basolateral
      cytoplasmic membrane, currently referred to as "pockets." This study provides a
      description of the exact spatial relationships between the M cells and the cells
      harboured in these so-called "pockets." Pieces of Peyer's patches, taken from the
      small intestine of an adult male rabbit, were treated as usual for conventional
      electron microscopy. Consecutive semithin and ultrathin sections were made
      through the entire thickness of the follicle-associated epithelium along planes
      parallel to the mucosal surface. Micrographs, taken from the ultrathin sections,
      were transposed into a software MacDraw Pro to obtain a computerized three
      dimensional reconstruction. Three-dimensional reconstruction of the M cells
      showed that the "pockets" were not formed by mere invaginations of the
      cytoplasmic membrane, but that they resulted from the branching of the
      supranuclear portion of the M cell cytoplasm around the M cell-infiltrating
      lymphocytes. These intrusive cells could be found inside the "pockets" or lined
      up with one another, in vertical columns, bordering on the basal aspect of the M
      cells. The particular arrangement of the M cell apical cytoplasm created a
      labyrinth within the follicle-associated epithelium, which could be assumed as a
      real intraepithelial compartment expandable virtually throughout all the
      epithelium. The functional meaning of the intraepithelial compartment delimited
      by the M cells and its possible role is discussed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8540630
TI  - Loss of laminin and type IV collagen in uterine luminal epithelial basement
      membranes during blastocyst implantation in the mouse.
AB  - BACKGROUND: Removal of the uterine luminal epithelium and its basement membrane
      is necessary for successful implantation of invasive blastocysts. Few reports,
      however, have specifically addressed the penetration and loss of the uterine
      luminal epithelial basement membrane (UEBM). We investigated the loss of UEBM by
      examining the distribution of laminin and type IV collagen. METHODS: Blastocyst
      implantation sites were collected from mice on days 5, 6, and 7 of pregnancy.
      Paraffin sections were prepared from these tissues and processed with standard
      immunoperoxidase techniques to reveal the distribution of laminin and type IV
      collagen. RESULTS: On day 5 of pregnancy blastocysts were adherent to the uterine
      epithelium. The epithelium and UEBM were complete and uninterrupted. On day 6 the
      juxtaembryonic uterine epithelium was lost and focal discontinuities were seen
      along the UEBM. By 1200 hr the UEBM had receded to the region near the
      ectoplacental cone, but staining was reduced for both antigens over the entire
      region surrounded by decidual cells. This decreased staining of the UEBM occurred
      in areas not yet occupied by trophoblast cells. On day 7 the UEBM was lost over
      the entire embryonic half of the uterine lining, corresponding to the
      distribution of decidual cells. CONCLUSIONS: Progressive loss of the UEBM
      occurred in a consistent spatiotemporal pattern following the onset of blastocyst
      implantation. Diminished immunoreactivity of laminin and type IV collagen in the
      UEBM was closely correlated with the area occupied by decidualized endometrial
      stroma and occurred in areas not yet in contact with trophoblast cells. We
      conclude that decidual cells are instrumental in the removal of UEBM during early
      pregnancy.

PMID- 8540631
TI  - Dynamics of follicular growth and atresia of large follicles during the ovarian
      cycle of the guinea pig: fate of the degenerating follicles, a quantitative
      study.
AB  - BACKGROUND: A quantitative integrated study of healthy ovarian follicles of
      different sizes and their mitotic activity and of clearly defined atretic stages
      of involuting large growing follicles at different stages of the guinea pig
      ovarian cycle is not available in the literature. We considered that such a study
      would reveal new aspects of ovarian tissue dynamics and provide new information
      in an organ with a continuous phenotypic transformation of its cellular
      components. METHODS: Ovaries from guinea pigs were removed on days 1 (opening of
      the vagina), 3, 6, 9, 13, and 16 of the cycle, and the following were measured in
      serial sections: (1) total number of healthy follicles falling into categories
      based on the volume occupied by granulosa cells, (2) total number of atretic
      follicles falling into clearly defined morphological stages of the degenerative
      and involutionary process affecting medium to large follicles, and (3) proportion
      of metaphase-arrested granulosa cells, after colcemid injection, in healthy
      follicles of different size categories. RESULTS: Dynamic patterns of follicular
      growth and degeneration were revealed that permitted the following main
      conclusions and observations: (1) small to middle-size follicles can reach the
      maximal category mass of granulosa mass within 6-7 days, and the number of
      granulosa cells can increase 6-7-fold during this interval, (2) the cohort that
      gives rise to 2-6 preovulatory follicles and to the large follicles that will
      undergo atresia during each cycle varied from 68 to 108 follicles, (3) cell death
      starts in the granulosa cell layers of large follicles even when neighbouring
      cells maintain a high mitotic activity and it spreads rapidly; dead granulosa
      cells are cleare by nucleolysis and cytolysis in the absence of blood leucocytes
      or neovascularization, (4) foci of atresia are observed also in a few
      preovulatory follicles, (5) antral cavities of follicles with dead granulosa
      cells in the process of being lysed shrink and are filled within 2-3 days with
      large fibroblast-like cells arising from phenotypic transformation of inner
      layers of theca interna, with no evidence of mitotic activity or angiogenesis;
      the outer layers of theca interna involute, and by progressive atrophy and a
      process of cell death, minute nodular structures arise with remnants of the ovum
      and zona pellucida, and (6) a transient wave of degeneration affects a proportion
      of small and middle-size follicles during the metestrous period. This process
      does not resemble the morphological phenomenology of follicular involution, which
      affects only large follicles. CONCLUSIONS: This study contributes to a fuller
      understanding of the dynamics and time relationships of follicular growth and
      loss in the guinea pig ovary and provides new morphogenetic information on the
      atretic process. It would be valuable for the design of experiments on endocrine
      and paracrine interactions involved in follicular growth and atresia.

PMID- 8540632
TI  - Morphometric characterisation of the fine structure of human type II pneumocytes.
AB  - BACKGROUND: Pulmonary type II pneumocytes have been examined by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and morphometry in
      numerous mammals. Until now, the fine structure of the human type II pneumocyte
      has not been studied by means of morphometry. METHODS: Eleven human donor lungs,
      which could not be made available for a suitable recipient, were preserved with
      Euro Collins solution (ECS) according to clinical organ preservation techniques.
      The lungs were fixed via the airways. Systematic random samples were analyzed by
      SEM, TEM, and classical stereological methods. RESULTS: Type II pneumocytes
      showed normal fine structural characteristics. Morphometry revealed that although
      inter-individual variation due to some oedematous swelling was present, the cells
      were in a normal size range as indicated by an estimated mean volume of 763 +/-
      64 microns 3. The volume densities were: nucleus 21.9 +/- 2.2%, mitochondria 5.8
      +/- 0.9%, lamellar bodies 9.8 +/- 3.6%, and remaining cytoplasmic components 62.4
      +/- 2.9% of the cell volume. Since the inter-individual variations in the volume
      densities referred to the cell may, to variable degrees, reflect the variation in
      the reference space, the volume densities referred to the constant test point
      system and the respective volume-to-surface ratios were used for inter-individual
      comparisons. These parameters indicate that lamellar bodies were independent of
      cellular swelling, while mitochondria < nucleus < remaining cytoplasmic
      components increased in size with increasing cell size. CONCLUSIONS: Two to 7.5
      hours of cold ischemia following ECS preservation do not deteriorate the fine
      structure of type II pneumocytes of human donor lungs. For reliable assessment of
      fine structural variations, morphometric parameters are required that are
      independent of variations in cell size.

PMID- 8540633
TI  - Three-dimensional organization of the elastic fibres in the rat lung.
AB  - BACKGROUND: The elastic framework of the distal lung has been studied by light
      microscopy (LM) and transmission electron microscopy (TEM). The preservation of
      the elastic fibres, for the three-dimensional observation in their relative
      positions, is difficult because they lack support when the normal methods of
      tissue processing are used. The goal of the present study was to understand the
      three-dimensional ultrastructure and organization of the elastic fibres of the
      lung preserved in their relative positions. METHODS: A combination of
      intravascular resin injection and formic acid digestion was used. The resin cast
      of the microvasculature acted as a scaffold to preserve the in vivo arrangement
      of the elastic fibres that are, otherwise, easily collapsible. Scanning electron
      microscopy (SEM) samples were further processed for TEM in order to confirm that
      the fibres were indeed components of the elastic system. RESULTS: SEM
      demonstrated a fine framework of elastic fibres, representing remnants of the
      alveolar walls, with the casted capillaries interwoven with the network of
      elastin. Each individual elastic fibre is composed of a small bundle of discrete
      fibrils. Some of these fibrils emerge from the fibre and join other fibres,
      producing an anastomosing appearance. Several elastic fibres link the walls of
      the intrapulmonary conducting airways, the vessels walls and the alveolar
      network, thus establishing an interrelated and interlaced framework. CONCLUSIONS:
      The method we have applied to visualize the elastic fibres of the lung is a
      unique approach to define the spatial organization of the pulmonary elastic
      fibres. We have demonstrated here the close relationship between the elastic
      fibres and the capillaries of the septal alveoli. The arrangement of the
      interwoven network of elastin and its relationship with the capillaries offers
      the structural setting for the distending capacity of the alveolar wall.

PMID- 8540634
TI  - Central cardiovascular shunts in the perinatal marsupial.
AB  - BACKGROUND: Marsupials are born at an early stage of development after a short
      period of gestation. In this study the nature and timing of closure of the
      central cardiovascular shunts was investigated. METHODS: Light and scanning
      electron microscopy were used to determine changes in central cardiovascular
      shunts in eight marsupial species with gestation periods of between 12.5 and 36.5
      days and birth weights ranging from 12.5 mg to 740 mg. Laboratory mice with a
      birth weight of about 1,000 mg and a gestation period of 21 days were included
      for comparison. RESULTS: Marsupials have a ductus arteriosus and an interatrial
      communication. The former closes rapidly after birth in the marsupial; however
      the interatrial communication is in the form of a fenestrated septum, which
      closes as a result of tissue proliferation over a period of days after birth. An
      additional central shunt, an interventricular foramen, was found to persist in
      three species for a short time after birth. In one species, the eastern native
      cat, Dasyurus viverrinus, which has a gestation period of about 19 days and low
      birth weight of about 12.5 mg, in addition to the two common shunts there was a
      large interventricular communication and septation of the outflow tract was
      incomplete. CONCLUSION: In adapting from intra-uterine life, it seems that
      marsupials have adopted different, but equally effective strategies, with regard
      to the circulatory system.

PMID- 8540635
TI  - In normal development pulmonary veins are connected to the sinus venosus segment
      in the left atrium.
AB  - BACKGROUND: Classic theories describe that the common pulmonary vein develops as
      an outgrowth from either the sinus venosus or atrial segment. Recent studies show
      that the pulmonary veins are connected to the sinu-atrial region before its
      differentiation into a sinus venosus and atrial segment. METHODS: The development
      of the sinu-atrial region with regard to the developing common pulmonary vein and
      the growth of the atrial septum was investigated in avian embryos, using both
      scanning electron microscopy and immunohistochemistry. Embryos ranging between
      stage HH12 and HH28 were incubated with QH-1 that recognizes quail endothelial
      cells and precursors, HNK-1, that appears in this study to detect the myocardium
      of the sinus venosus, or with HHF-35, being specific for muscle actins. Also
      vascular casts of the heart were produced by injecting prepolymerized Mercox into
      the vascular system. RESULTS: In preseptation stages the common pulmonary vein
      drains into the left part of the sinus venosus, that is clearly demarcated by the
      sinu-atrial fold and HNK-1 expression. During atrial septation the left part of
      the sinus venosus, in contrast to the right part, loses its HNK-1 antigen from
      stage HH23 onwards, while at the same time the sinu-atrial fold in the left
      atrial dorsal wall flattens and disappears. From stage HH25 onwards HNK-1
      expression is restricted to the right part of the sinus venosus, which
      contributes to the right atrium. The myocardial atrial septum never expresses the
      HNK-1 antigen, suggesting that the septum is of atrial origin. DISCUSSION: It
      appeared that the sinus venosus does not only contribute to the sinus venarum of
      the right atrium, but also to the left atrium.

PMID- 8540637
TI  - [37th National Congress of Anesthesia and Resuscitation. Xth Meeting French
      Quebec. Paris, 14-17 September 1995. Abstracts].

PMID- 8540636
TI  - Growth of the myocardial volumes of the individual cardiac segments in the rat
      embryo.
AB  - BACKGROUND: Although the growth of the developing heart in relation to an
      increase of ventricular systolic pressure and the growth of the entire embryo
      during development has been described, no data are available on the growth of the
      individual segments and intersegmental junctions. Because these different
      portions are known to function differently, the need for data on their individual
      development is obvious. METHODS: We have measured the volumes of these different
      compartments by Cavalieri's point counting method in rat embryos from 11 to 17
      days. RESULTS: It is shown that sinus venosus and sinu-atrial junction as well as
      the main compartments atrium, inlet, and proximal outlet segment grow roughly
      proportional to the total myocardial volume. Atrio-ventricular canal and distal
      outlet segment show a restricted growth and their proportional volumes decrease
      in time. The inlet segment is the most important part of the ventricular mass at
      11 days of gestation, when it is still larger than the proximal outlet segment
      and, thus, takes the greater part in systolic action of the ventricular mass. The
      growth of the primary fold increases from day 13 onwards and can be considered as
      part of the wall of the inlet segment which gives rise to the main part of the
      ventricular septum. CONCLUSIONS: The timing of the septal volume increase fits
      with qualitative descriptions of ventricular septation. The atrio-ventricular
      canal and distal outlet segment have an important constrictive function in early
      stages, when valves are not yet present. Slow conduction and contraction patterns
      have been reported to be a characteristic feature of these portions of the
      embryonic heart. With development of valves these segments are loosing their
      mechanical function and, thus, their proportional volume declines.

PMID- 8540638
TI  - Unequivocal priorities in times of unprecedented change.

PMID- 8540639
TI  - The beneficial effect of enhanced macrophage function on the healing of bowel
      anastomoses.
AB  - Inadequate healing and subsequent leakage of bowel anastomoses are serious
      postoperative complications in abdominal surgery. Previous studies have
      demonstrated the macrophage to be a key cell in the physiology of wound healing.
      The current study was undertaken to evaluate the effects of enhanced macrophage
      function on the healing of bowel anastomoses. Sprague-Dawley rats (250 gm)
      underwent laparotomy and jejunojejunostomy following IV treatment with glucan
      (100 mg per kg), a potent macrophage stimulant, or 5 per cent dextrose 24 hours
      before surgery and again on the day of surgery. Animals were killed and the
      anastomoses underwent wound tensiometry on Day 3 using a computer-assisted
      constant velocity tensiometer. The glucan treated animals had a significantly
      greater anastomotic breaking strength (88.5 gm +/- 10.7 versus 45.45 gm +/- 5.1)
      (P < 0.01). Formalin fixation increased the breaking strength of the untreated
      anastomosis but not of the treated anastomosis (92.9 gm +/- 11.77 versus 92.3 +/-
      12.44). Analysis of macrophage supernatant for the growth factors epidermal
      growth factor (EGF), platelet derived growth factor (PDGF), and transforming
      growth factor-beta (TGF-beta) was accomplished by immunoblot assay. Results
      indicated no difference in the presence of EGF in the stimulated and unstimulated
      macrophage supernatants. PDGF and TGF-beta were decreased in the stimulated
      macrophage supernatants. We conclude that 1) Enhanced macrophage function had a
      beneficial effect on the early tensile strength of bowel anastomoses. 2) Effects
      of the activated macrophage on bowel anastomoses may not be related to secretion
      of conventional growth factors. 3) Immunopharmacologic agents that enhance
      macrophage function may be an important adjunct to surgical therapy requiring
      bowel anastomosis.

PMID- 8540640
TI  - Prediction of long-term ventilatory support in trauma patients.
AB  - Mechanical ventilatory support requiring tracheal intubation may be necessary for
      variable lengths of time in injured patients. Criteria useful in predicting the
      need for prolonged tracheal intubation has not been clearly established in the
      trauma population. Early identification of patients requiring prolonged tracheal
      intubation and mechanical ventilatory support could lead to earlier tracheostomy
      and subsequent reductions in complications associated with prolonged endotracheal
      intubation. This study evaluated the ability of clinical measures of injury
      severity, mental status, oxygenation, and ventilation to predict the need for
      prolonged mechanical ventilatory support (> or = 14 days) early in the postinjury
      course of the adult trauma patient requiring endotracheal intubation and
      mechanical ventilatory support within the first 24 hours of injury. All adult
      trauma patients admitted to our Level I trauma center over a 4-year period
      between January 1990-December 1993 were evaluated. A total of 212 patients met
      study criteria that included intubation within the first 24 hours of injury,
      ventilatory support requirement > or = 72 hours, and a survival time of at least
      14 days postinjury. Data pertaining to measures of injury severity (RTS, AIS,
      ISS), mental status (GCS), oxygenation [(A-a)O2], and ventilation (VE,EDC) were
      recorded for postinjury Day 1 and Day 5. There were 157 males and 55 females (age
      range of 16-91 years, mean 39.5 years). Mechanism of injury was blunt in 198 and
      penetrating in 14 patients. One hundred patients required prolonged mechanical
      ventilatory support. Data were analyzed by stepwise logistic regression analysis.
      Age and GCS values on Day 1 predicted the need for long term mechanical
      ventilatory support in a select group of patients, age 20 and GCS of 3 (P <
      0.05). At Day 5, age, GCS, and (A-a)O2 gradient were predictive of the need for
      prolonged mechanical ventilatory support (P < 0.05). On Day 5, GCS of 3 predicted
      the need for long-term mechanic al ventilatory support regardless of age or (A
      a)O2 gradient. GCS < or = 5 and (A-a)O2 > or = 150 predicted prolonged mechanical
      ventilatory support in young patients (age 20). At ages of 40 to 60, GCS < or = 7
      and (A-a)O2 > or = 150 indicated the need for long term mechanical ventilatory
      support. In older patients (age > or = 80), GCS < or = 7 and (A-a)O2 gradient >
      or = 100 were predictive of long-term mechanical ventilatory support. Appropriate
      use of these clinical indicators may assist in early identification of patients
      requiring prolonged mechanical ventilatory support, and subsequent conversion
      from endotracheal intubation to tracheostomy with anticipated reduction in
      complications.

PMID- 8540641
TI  - Perforated jejunal diverticula.
AB  - Jejunal diverticular (JD) perforation is an uncommon cause of acute abdominal
      pain in the elderly. From 1971 to 1994 we treated 13 such patients, 9 men and 4
      women, with a mean age of 68 years. All patients experienced sudden onset of
      abdominal pain, nausea and vomiting, and leukocytosis (range of white blood cell
      counts, 14,000-21,000). On physical examination, three patients had localized
      peritonitis, were thought to have appendicitis, and underwent immediate
      laparotomy and segmental jejunal resection for perforated JD. The remaining 10
      patients had abdominal tenderness without peritoneal signs. They were
      hospitalized and managed expectantly. All experienced worsening signs and
      symptoms and underwent exploratory laparotomy and resection of the involved
      jejunal segment 13 hours to 8 days after admission. Although 6 of 13 patients had
      had JD documented previously, in only 2 patients was perforated JD diagnosed
      preoperatively. In 8 of 13 patients peritoneal contamination was minimal and was
      contained within the leaves of the mesentery. Soilage was severe with abscess
      formation in 5 patients. The longer the delay in operative intervention, the
      greater the peritoneal soilage. The 3 patients undergoing immediate surgery had
      minimal contamination. Of the 10 patients initially observed, the mean interval
      before operation was 74 hours in the 5 patients with severe soilage versus 21
      hours in those with minimal contamination. The postoperative course was
      uneventful in 11 patients. Two patients died. Surgical consultation was delayed
      (8 days, 12 days) in both patients, who had severe peritoneal contamination and
      died of sepsis. In conclusion, JD perforation is an uncommon and frequently
      overlooked cause of acute abdominal pain in elderly patients. Timely operative
      intervention and resection of the involved jejunum are the keys to a successful
      outcome. Because the presentation and physical findings of perforated JD can be
      highly variable, a history of preexisting JD should arouse suspicion for JD
      perforation as the etiology of acute abdominal pain in the elderly.

PMID- 8540642
TI  - Choledochal cysts: a ten year experience.
AB  - Choledochal cyst (CC) is a rare disorder that usually presents in childhood.
      Prognosis depends on early diagnosis, complete excision of the cyst, and
      reconstruction by hepaticojejunostomy. This report details our 10-year experience
      and emphasizes innovations in our management. Sixteen patients presented with CC
      at a mean age of 3 years. (Range, newborn to 21 years, with a M:F ratio 1:4). Two
      groups could be identified on the basis of age at presentation. Group I (N = 7),
      presented in the neonatal period, three with obstructive jaundice and four
      without symptoms. In Group II (N = 9), all patients presented with ascending
      cholangitis at a mean age of 6 years. Thirteen patients had a type 1 CC, one
      patient had a type 3 CC, and two had type 4 CC. The patients with type 1 and type
      4 CC underwent primary cyst excision with Roux-en-Y hepaticojejunostomy, whereas
      the patient with type 3 CC underwent cyst excision with sphincteroplasty of the
      ampulla. There was only one complication of postop cholangitis that cleared with
      antibiotic therapy. All patients have remained free from symptoms in the follow
      up period (6 months-10 years). Our four most recent cases were diagnosed in utero
      by prenatal ultrasonography. This led to appropriate antenatal counseling and
      prospectively planned neonatal surgery. These infants were asymptomatic, with no
      clinical signs at birth, and antenatal ultrasonography prevented diagnostic
      delay. Excision of the choledochal cyst and primary hepatico-enteric anastomosis
      is confirmed as the therapy of choice. Antenatal sonography is a sensitive method
      in the diagnosis of CC and offers the opportunity for early diagnosis and planned
      surgery before the onset of complications.

PMID- 8540643
TI  - In situ prosthetic graft replacement for mycotic thoracoabdominal aneurysms.
AB  - Infected aortic aneurysms remain a difficult surgical problem associated with
      high morbidity and mortality. We report three cases of mycotic thoracoabdominal
      aneurysms treated by debridement of infected aortic tissue, in situ prosthetic
      graft replacement, and intensive antibiotic therapy. One early death occurred in
      a patient with systemic sepsis related to Salmonella enteritidis infection of the
      thoracic aorta secondary to a colovesical fistula. The two other patients remain
      alive at 2 years without further complications of the surgery. Bacteriology is as
      follows: Staphylococcus aureus, Streptococcus pneumoniae, and Salmonella
      enteritidis. In all patients the operation was performed immediately after the
      diagnosis was confirmed. Antibiotic therapy was begun intraoperatively and was
      continued for at least 6 months. Two patients were followed regularly, and there
      have been no septic recurrences in our 2-year follow-up period. In situ
      prosthetic graft replacement in conjunction with intensive antibiotic therapy is
      a viable option in the treatment of mycotic thoracoabdominal aortic aneurysms.

PMID- 8540644
TI  - Analysis of complications and long-term outcome of trauma patients with needle
      catheter jejunostomy.
AB  - Enteral feedings demonstrably lower the risk of septic complications. However,
      complications associated with the specific method of enteral feeding may diminish
      the intended benefits. The objective was to determine the short and long-term
      complications associated with needle catheter jejunostomy (NCJ). All NCJs placed
      at a Level I trauma center over an 8-year period were reviewed. Short-term
      complications directly attributable to NCJ were defined as tube leakage with
      intraabdominal or intraparietal spillage, intraabdominal abscess, small bowel
      obstruction at the catheter site, tube blockage or dislodgement, or soft tissue
      infection. Telephone interviews were conducted to elicit long-term complications,
      including operations to correct a complication of the NCJ, chronic nausea,
      vomiting, diarrhea, bloating, hernia, or change in appetite. Of 122 study
      patients, short-term complications (N = 22) included two abscesses, one bowel
      obstruction, two abdominal wall infections, three leaks, one local soft tissue
      infection, one enterocutaneous fistula, three blocked catheters, and nine tube
      dislodgements. Fifty patients were contacted by telephone; 19 had long-term
      complications, including two operations for adhesions. Complications associated
      with NCJ are common, may be life-threatening, and may require surgical
      intervention. In many cases, other methods of enteral feeding access may be
      preferable to NCJ.

PMID- 8540645
TI  - Postoperative pulmonary complications and morbidity after abdominal
      aneurysmectomy: a comparison of postoperative epidural versus parenteral opioid
      analgesia.
AB  - Patients undergoing aortic aneurysm repair have a high prevalence of coexisting
      cardiac and pulmonary disease, and the postoperative recovery is especially
      delayed by pulmonary complications. A review of all elective abdominal aneurysm
      repairs over a 29-month period was undertaken to evaluate the effectiveness of
      postoperative epidural analgesia in decreasing morbidity and mortality, and
      specifically pulmonary complications. Patients were placed into two groups; Group
      1 (34 patients) used an epidural catheter for postoperative pain control, and
      Group II (31 patients) used standard parenteral opioid analgesia. The two groups
      were similar in preoperative combined factors including known risk factors for
      atherosclerotic cardiovascular disease, preexisting cardiac or pulmonary disease,
      and preexisting renal insufficiency. A statistically significant decrease (P = <
      0.05) was found in both cardiac (P = 0.0002) and pulmonary (P = 0.019)
      complications in comparison, favoring Group I patients. A significant decrease
      was also seen in the time to liquid intake (P = 0.044), time out of bed to a
      chair (P = 0.002), length of stay in the Intensive Care Unit (P = 0.024), and
      overall hospital charges (P = 0.046) in favor of Group I patients. Although no
      significant difference (P = > 0.05) was seen in decreasing time to ambulation (P
      = 0.054), average time required on the ventilator (P = 0.053), or hospital days
      (P = 0.181), all of these did show a trend in favor of epidural catheter
      utilization. There were no complications or infections related to the use of the
      epidural catheter during this study period. In conclusion, the use of an epidural
      catheter for postoperative pain control has been shown to decrease time of
      intubation, time in the ICU, number of cardiac and pulmonary complications, which
      should lead to an overall decrease in hospital charges after elective repair of
      abdominal aortic aneurysms.

PMID- 8540646
TI  - Unplanned reoperation for bleeding.
AB  - Thirty (0.46%) patients required one or more reoperations to control bleeding
      after 6499 elective surgical procedures. A specific bleeding site was identified
      in 10 (0.15%), and bleeding was diffuse in 20 (0.31%). Bleeding occurred despite
      normal prothrombin and partial thromboplastin times and adequate platelet counts
      in all 30 cases. Diffuse bleeding was associated with the preoperative use of
      aspirin alone or in combination with other nonsteroidal anti-inflammatory drugs
      (NSAIDS) in 19 of 20 patients (95%). None of the patients with a discrete
      bleeding point identified at reoperation were taking these products (P < 0.001).
      More than one reoperation was more often required in the patients with diffuse
      postoperative bleeding than those with a specific site of hemorrhage. Many of
      these subsequent procedures were required to manage infections that developed
      after the first reoperation to control bleeding. Intensive care unit use, length
      of intensive care unit stay, total hospital stay, and hospital charges were all
      significantly increased when diffuse postoperative bleeding was noted.
      Postoperative bleeding, especially when it is diffuse rather than from a specific
      bleeding point, significantly prolongs hospital stay and increases costs.
      Bleeding is not prevented by obtaining routine screening coagulation profiles. A
      medication history with special attention to the recent use of aspirin and NSAIDS
      is advised before elective operations. Delaying surgery until the antiplatelet
      effects of these drugs have worn off may be advisable.

PMID- 8540647
TI  - The use of computed tomography in blunt abdominal injuries.
AB  - A retrospective study was performed to evaluate the use of abdominopelvic
      computed tomography of the abdomen (CTA) in the initial evaluation of
      hemodynamically stable blunt trauma patients. Two hundred fifty-six of 2,047
      injury admissions over a 2-year period underwent CTA. Sixty-two (24.2%) scans
      were positive for visceral injury. Sensitivity of CTA for patients with visceral
      injury was 92.4 per cent, specificity was 99.5 per cent, and overall accuracy was
      97.6 per cent. Of all injuries documented by CTA or laparotomy, CTA detected 83.7
      per cent. Injury-specific sensitivities were lowest in injuries of the pancreas
      (0%), intestinal tract (41.6%), and bladder (50%). False negative scans occurred
      in 1.9 per cent of patients, with no deaths or major complications attributable
      to delay in diagnosis. Nonoperative management was possible in 72 per cent of 57
      patients with solid viscus injuries; splenic preservation was possible in 81.5
      per cent of injured organs. Urine dipsticks and urinalysis performed poorly as
      predictors of either significant urological injury or intra-abdominal injury in
      general. When indications included early need for nonabdominal operation, only
      three of 41 scans were positive. Yield for patients scanned with obtundation as
      an isolated indication was diminished. Cost of CTA exceeds that of DPL, but lower
      procedure-related risk and lower estimated rate of nontherapeutic laparotomy
      leads to clinical favor of CTA in this group of patients.

PMID- 8540648
TI  - The spectrum of Helicobacter pylori in upper gastrointestinal disease.
AB  - Helicobacter pylori has been recognized as a contributing factor in
      gastrointestinal disease. Yet, questions remain as to its clinical significance.
      This prospective study was done to determine the prevalence, distribution,
      clinical significance, and treatment response of H. pylori gastrointestinal
      infection. A total of 91 patients with upper gastrointestinal symptoms underwent
      122 esophagogastroduodenoscopies (EGD). Biopsies were taken for H. pylori from
      the gastric fundus, body, antrum, prepylorus, and duodenal bulb; 45.3 per cent of
      patients with abdominal pain, 27.8 per cent with "heartburn," and 55.6 per cent
      with anemia/GI bleed had H. pylori infections. Pertaining to EGD findings: 54.2
      per cent of patients with gastroduodenal ulcer, 56.4 per cent with
      gastritis/duodenitis, 37.5 per cent with esophagitis/esophageal ulcer, but only
      17.6 per cent with normal findings had H. pylori infection. The distribution of
      H. pylori: fundus (53.3%); body (55.6%); antrum (85.4%); prepylorus (78.4%);
      duodenum (15.6%). Treatment for H. pylori was amoxicillin, metronidazole, colloid
      bismuth with an antisecretory drug. H. pylori was eradicated in 78.9 per cent of
      patients; 93.3 per cent of these patients had symptomatic improvement and/or
      ulcer healing. Using stepwise logistic regression, H. pylori eradication was an
      independent predictor of symptomatic improvement.

PMID- 8540649
TI  - Laparoscopic L5-S1 diskectomy: a cost-effective, minimally invasive general
      surgery--neurosurgery team alternative to laminectomy.
AB  - Laparoscopic L5-S1 diskectomy (LLD) is a promising new technique for managing
      disabling pain from herniated lumbar disks. It is unknown, however, whether the
      clinical results of LLD are superior to those of traditional laminectomy (LAM).
      This study was undertaken, therefore, in order to compare LLD and LAM in the
      management of L5-S1 disk herniation unresponsive to conservative treatment
      measures. Clinical records of 22 patients who underwent 23 LLD procedures and of
      23 LAM patients were reviewed with respect to demographics and median age,
      operative blood loss, operative time, hospital stay, and time of rehabilitation
      to work/normal activity, as well as postoperative morbidity, recurrent symptoms,
      long-term functional status, and inhospital patient charges. Two LLD patients had
      undergone LAM previously, and one had a percutaneous microdiskectomy. All LLD
      patients had relief of disk pain immediately after surgery. Morbidity after LLD
      included transient brachial plexus neuropraxia (1), urinary retention (1), and
      rectus hematoma (1). No LAM complications were reported. Among LLD patients,
      compared with LAM, median age (34.5 years versus 40 years), estimated blood loss
      (12 mL versus 68 mL), hospital length of stay (1 day versus 3 days), time to
      normal activity (17 days versus 79 days) and mean inhospital patient charges
      ($5,737 +/- 283 versus $7,762 +/- 662) were reduced significantly (P < 0.05). LLD
      operating time was significantly longer than LAM (210 versus 160 minutes median,
      P < 0.01). With a median follow-up time of 11.0 months (range, 2 to 23 months)
      all LLD patients had returned to normal activity, whereas 7 of the LAM group
      (30%) remained disabled (P < 0.01). Sixty-eight per cent of LLD patients were
      pain-free during follow-up, compared with 39 per cent of the LAM group (P <
      0.05). Sixty-four per cent of LLD patients and 57 per cent of the LAM group
      needed postoperatively physical therapy. One LLD and 4 LAM patients required
      reoperation, by LLD and LAM, respectively, for recurrent disk herniation. LLD is
      a safe, cost-effective, minimally invasive operation for managing disabling L5-S1
      disk herniation. Compared with LAM, LLD reduces blood loss, length of stay,
      rehabilitation time, and patient charges, and improves long-term functional and
      pain-free status. LLD should be considered as an alternative to LAM for patients
      with herniated L5-S1 intervertebral disks unresponsive to conservative
      management.

PMID- 8540650
TI  - Technical considerations of the different approaches to laparoscopic
      herniorrhaphy: an analysis of 500 cases.
AB  - Between April 1991 and April 1994, 500 laparoscopic herniorrhaphies have been
      performed at our institution. The transabdominal preperitoneal approach was used
      for 290 repairs, and the total extraperitoneal approach was used for 210 repairs.
      Although both repairs resulted in acceptable recurrence and complication rates,
      we adopted the total extraperitoneal approach in June 1993, with a resulting
      lower recurrence rate (0.5% versus 2.1%) and lower complication rate (3.1% versus
      11.1%) when compared with the transabdominal approach. In this retrospective
      review, four epigastric vessel injuries (1.6%) and one bowel obstruction from a
      port hernia (0.5%) were attributed to the lateral port placement in the
      transabdominal approach. There were also two visceral injuries (1.0%) from
      entering the abdominal cavity in the transabdominal approach. The one visceral
      injury (0.6%) in the total extraperitoneal approach was a result of the balloon
      dissection in a patient with multiple previous lower abdominal operations. Better
      exposure and lateral visualization of the extraperitoneal space has led to less
      incidence of nerve injury (0.0% versus 2.4%) and a lower recurrence rate (0.5%
      versus 2.1%) in the total extraperitoneal approach. The total extraperitoneal
      approach to laparoscopic herniorrhaphy compares favorably to the transabdominal
      approach in our institution. The improved results may have been due to the
      technical differences between these approaches.

PMID- 8540651
TI  - Supraventricular tachyarrhythmias in the surgical intensive care unit: an under
      recognized event.
AB  - Over a 1-year period, 28 patients (13.6% of admissions to one surgical intensive
      care unit) developed the new onset of a supraventricular tachyarrhythmia
      requiring treatment. None was associated with intravascular catheter placement.
      There were 16 women and 12 men with an average age of 69.8 years (range 49-92).
      In nine of the patients, the diagnosis was made coincidental with or immediately
      before the onset of postoperative sepsis. Twenty-six patients responded to
      medication and two required cardioversion. Mortality was 28.6 per cent (8/28),
      but none as a direct result of the arrhythmia. One patient had a myocardial
      infarction secondary to the arrhythmia. Supraventricular tachyarrhythmias are a
      relatively common problem in the critically ill surgical patient. Surgeons who
      care for such individuals need to be familiar with the differential diagnosis and
      treatment of arrhythmias. The new onset of a supraventricular tachyarrhythmia in
      an otherwise stable patient should prompt a search for a treatable cause of
      sepsis.

PMID- 8540652
TI  - A retrospective study of the efficacy of transjugular intrahepatic portosystemic
      shunts.
AB  - Transjugular intrahepatic portosystemic shunts (TIPS) are being used increasingly
      for complications of portal hypertension, including active and recurrent variceal
      hemorrhage and intractable ascites, as well as for portal decompression in
      patients awaiting orthotopic liver transplantation. We reviewed the initial 2
      year experience with TIPS at Louisiana State University Medical Center-Shreveport
      and Willis-Knighton Medical Center, Shreveport, Louisiana, which involved 31
      patients. Clinical findings (with some patients having more than one finding)
      revealed that 16 per cent (five) of the patients had active hemorrhage; 61 per
      cent (19), multiple episodes of (recurrent) variceal hemorrhage; and 48 per cent
      (15), ascites. The mean follow-up period was 6.2 months, with a patient mortality
      of 13 per cent. Results showed that in 87 per cent (27 of 31) of patients the
      TIPS procedure was successfully placed. There was 100 per cent control of active
      variceal hemorrhage (five patients) and ascites (12 patients; excludes three
      patients who died). Rebleeding occurred in 18 per cent (four of 22) of patients,
      all related to stenosis or occlusion of the TIPS. The overall incidence of
      occlusion and stenosis was 11 per cent and 22 per cent, respectively. Seventy
      seven per cent (seven of nine) of the patients experiencing the latter
      complications underwent successful angioplasty or revision of their TIPS. The
      results of our experience indicate that TIPS placement can be performed
      successfully with low procedural morbidity. The procedure is effective in
      controlling active variceal hemorrhage refractory to endoscopic sclerotherapy.
      The use of TIPS may be particularly beneficial for patients who are either
      awaiting liver transplantation or poor candidates for surgical shunt procedures.
      TIPS may not be a long-term solution for patients with portal hypertension, given
      the current rates of occlusion and stenosis.

PMID- 8540653
TI  - Inhibition of TNF alpha improves survival in an experimental model of acute
      pancreatitis.
AB  - The development of systemic complications in acute pancreatitis is largely
      responsible for the mortality associated with this disease. The systemic sequelae
      encountered in acute pancreatitis are similar to those occurring in patients with
      septic shock, a syndrome of multiple organ failure thought to be related to
      overproduction of inflammatory cytokines. As with sepsis, data is mounting that
      cytokines, particularly TNF alpha, may play a central role in acute pancreatitis
      and mediate the systemic sequelae of the disease. We have previously shown
      elevated levels of TNF alpha in the serum of animals with experimental acute
      pancreatitis. In this study, we use a bile-infusion model of pancreatitis in the
      rat to show amelioration of disease severity as well as a distinct survival
      advantage by TNF alpha blockade using anti-TNF alpha polyclonal antibody. These
      data provide strong evidence that TNF alpha is a major contributor to the
      morbidity and mortality from acute pancreatitis.

PMID- 8540655
TI  - Current challenges for outcome measurement in surgical practice.

PMID- 8540654
TI  - The tumor biology of melanoma nodal metastases.
AB  - Approximately 20 per cent of melanomas greater than 0.76 mm in thickness will
      metastasize to the regional lymph nodes if treated with wide local excision alone
      (WLE). Elective lymph node dissection (ELND) is associated with significant
      morbidity, which includes lymphedema, wound complications, and paresthesias of
      the extremity. An alternative operative approach uses selective lymphadenectomy
      with the identification of the sentinel node, defined as the first node in the
      lymphatic basin that drains the primary cutaneous site. This study consisted of
      132 patients with melanomas greater than 0.76 mm. One hundred nine patients (83%)
      had histologic negative sentinel nodes, and 23 patients (17%) had one or more
      sentinel nodes positive for disease. In patients with metastatic disease, 30/35
      (86%) sentinel nodes were positive, and 25/357 (7%) nonsentinel nodes were
      positive (P < 0.001). In 18 patients (78%) of the 23 patients with metastatic
      disease, the sentinel node was the only node positive, strongly suggesting that
      there is an orderly progression of metastases. Two patients developed metastatic
      nodal disease after removal of a negative sentinel node (false negative rate =
      1.5). The mean follow-up was 1 year. Sentinel node histology reflects the
      histology of the remainder of the nodes in the lymphatic basin and "skip"
      metastases, defined as a negative sentinel node but positive nodes higher in the
      regional chain positive for metastases or an axillary recurrence after a negative
      sentinel node biopsy, are rare for malignant melanoma. Harvesting the sentinel
      node in patients with intermediate or greater thickness melanoma will, therefore,
      identify a subset of patients with metastatic disease who have the most to
      benefit from a complete node dissection. This surgical approach allows for
      complete pathological staging and therapeutic management of patients while
      significantly reducing expense and overall morbidity.

PMID- 8540656
TI  - Management of oral cancer.
AB  - Oral cancer is a serious disease that is on the increase. The most pressing need
      is early recognition and referral for specialist treatment. Too many cases
      present with advanced tumours. Radiotherapy and surgery remain the primary
      modalities of curative treatment, but understanding of tumour pathology and
      developments in surgical and radiotherapeutic technique have combined to produce
      a rational approach to management. In many instances 'radical' methods of
      surgical access can be combined with a more 'conservative' resection of the
      mandible or cervical lymph nodes. One-stage reconstructive procedures, often
      incorporating osteotomy techniques, miniature bone plating and free tissue
      transfer, have minimised the morbidity and functional deficit so often seen after
      earlier operations. All surgeons involved in the modern management of oral cancer
      should have expertise in these techniques or be part of a team which can provide
      them.

PMID- 8540657
TI  - Experience with 300 laparoscopic inguinal hernia repairs with up to 3 years
      follow-up.
AB  - The long-term results of 300 laparoscopic inguinal hernia repairs are reported
      with 11 cases followed up more than 3 years, 104 cases more than 2 years, and 225
      cases more than 1 year. There were five early failures owing to the use of too
      small a piece of mesh. There have been no long-term recurrences. The results
      indicate that transabdominal preperitoneal laparoscopic mesh repair of hernias is
      a satisfactory technique with a low recurrence rate and a low major complication
      rate (4%). Patients have found the procedure to be remarkably pain free and 51%
      have taken no analgesics after discharge from hospital. Of the patients, 78%
      returned to work within 2 weeks of the operation. These results suggest that
      laparoscopic hernia repair can be performed safely with excellent long-term
      results.

PMID- 8540658
TI  - Femorotibial bypass: the learning curve.
AB  - Femorotibial bypass is still infrequently performed in many district hospitals,
      because it is time consuming and the risk of failure is high, especially during
      the learning curve. This article reviews the results of a single consultant
      surgeon and his team after starting femorotibial bypass de novo in a district
      general hospital. During the period 1987 to 1992, 85 femorotibial grafts were
      performed in 76 patients for ulceration and gangrene (57), rest pain (19) and
      severe claudication (9). Sixty-six were autogenous vein, 15 were PTFE with distal
      vein cuff, two were composites and two were umbilical vein. Overall, 22 grafts
      (26%) failed within the first 30 days (two were salvaged) and 21 amputations were
      required (five despite patent grafts). There were three early deaths (mortality
      3.9%). At the end of 1993, 39 limbs had been amputated and 24 patients had died
      (eight with amputations). Twenty-three (44% of survivors) were alive with patent
      grafts. These disappointing early results were due to an initial technical
      learning curve, after which increased confidence may have led to reconstructing
      some patients with inadequate distal arteries. A more selective approach is now
      used. Limb salvage can be achieved in a worthwhile proportion of these patients
      and 3-year primary patency rates are similar to those of teaching hospitals in
      this country.

PMID- 8540659
TI  - Vascular trauma in civilian practice.
AB  - Vascular trauma is associated with major morbidity and mortality, but little is
      known about its incidence or nature in Britain. A retrospective study of 36
      patients requiring operative intervention for vascular trauma under one vascular
      surgeon over a 6-year period was undertaken. Twenty-four patients suffered
      iatrogenic trauma (median age 61 years); including cardiological intervention
      (19), radiological intervention (2), varicose vein surgery (1), umbilical vein
      catherisation (1) and isolated hyperthermic limb perfusion (1). There were 23
      arterial and three venous injuries. Twelve patients had accidental trauma (median
      age 23 years). Three of the ten patients with blunt trauma were referred for
      vascular assessment before orthopaedic intervention, two after an on-table
      angiogram and five only after an initial orthopaedic procedure (range of delay 6
      h to 10 days). Injuries were arterial in nine, venous in two and combined in one.
      Angiography was obtained in six patients, and in two patients with multiple upper
      limb fractures identified the site of injury when clinical localisation was
      difficult. A variety of vascular techniques were used to treat the injuries. Two
      patients died postoperatively and one underwent major limb amputation. Thirty-two
      (89%) remain free of vascular sequelae after a median follow-up of 48 months
      (range 3-72 months). Vascular trauma is uncommon in the United Kingdom. To repair
      the injuries a limited repertoire of vascular surgery techniques is needed.
      Therefore, vascular surgical assessment should be sought at an early stage to
      prevent major limb loss.

PMID- 8540660
TI  - Surgical treatment for venous ulcers: is it worthwhile?
AB  - We have reviewed the results of treatment of 159 consecutive limbs presenting
      with a clinical diagnosis of venous ulcer in 140 patients (70 male, aged 28-90
      years, median 66 years). Of the patients, 61% were referred because of severe
      pain and 53% of the ulcers had been present > 2 years. Patients were evaluated
      clinically and by Doppler, with selective use of venography,
      photoplethysmography, arteriography and latterly duplex scanning. Seventy-one
      limbs had surgery to the superficial veins, 18 limbs had arterial reconstruction,
      and 10 limbs had skin grafting alone. There was one operative death after
      arterial reconstruction but none after venous surgery. Patients were followed up
      for 1-5 years (median 3 years). Of those who had been treated surgically, healing
      was achieved in 88%, and ulcers healed in 52% of those treated non-operatively.
      In all, 18% of the ulcers recurred in each group. These results show a favourable
      association between appropriate venous and arterial surgery and the healing of
      venous ulcers, with relief of pain. They support a policy of thorough evaluation
      and appropriate surgical treatment in these patients.

PMID- 8540661
TI  - A regional study of thyroidectomy: surgical pathology suggests scope to improve
      quality and reduce cost.
AB  - This study of thyroid histopathological data from hospitals in the South West
      Thames region was undertaken to assess current practice and the scope for
      improvement. Over a 6 month period, 186 thyroid operations were performed on 179
      patients at eight hospitals serving almost 1.7 million people. The frequency of
      thyroidectomy in different hospitals varied from 13 to 35 per 100,000 per year
      and 6.4% of the operations were second thyroidectomies. Benign multinodular
      goitre was the most common histological finding (34%). A benign solitary nodule
      was found in 36% and malignancy in 8.4% of the specimens. Correlation of
      histological analysis and type of operation suggested that a variety of
      operations were performed for the same pathological condition and that some
      operations were diagnostic procedures only. Overall, 63 of the 186 operations
      (34%) might have been avoided by a firm preoperative diagnosis. Only 67 thyroid
      fine needle aspiration biopsies (FNAC) were performed at the eight hospitals
      during the study period. Only 15 (8%) of the patients who underwent thyroid
      operation had been investigated by FNAC. Reduction in thyroid surgery through
      more widespread use of FNAC could result in savings of 100,000 pounds per million
      population per year. Regional activity data show that more than 50 surgeons
      currently undertake a workload of less than 500 thyroidectomies each year.
      Increased subspecialisation may be required to reduce costs and raise standards.

PMID- 8540662
TI  - Extended lymph node dissection (D2 resection) should now be performed routinely
      in the curative surgical treatment of gastric carcinoma.
AB  - Gastric cancer has a dismal prognosis in the Western world. In contrast, in Japan
      where extended lymphadenectomy is the rule in curative gastric cancer surgery,
      the prognosis is much better. The arguments for and against the adoption of this
      procedure in the West are presented. This procedure is safe in the hands of
      experienced surgeons and by improving locoregional control, may improve survival.
      However, in the absence of controlled data supporting a survival advantage, the
      excess morbidity and mortality of this extended procedure in the West may not be
      justified.

PMID- 8540663
TI  - Factors predicting outcome after selective ERCP in the laparoscopic era.
AB  - This study assessed the outcome of 342 patients with in situ gallbladders
      undergoing ERCP for suspected choledocholithiasis. The result of ERCP was found
      to play a significant role (P < 0.0001) in determining whether patients were
      subsequently managed conservatively (n = 152) or underwent either laparoscopic (n
      = 110) or open (n = 80) surgery. Those undergoing laparoscopic surgery were noted
      to be younger (P = 0.0001) and were less likely to be jaundiced (P = 0.0015) or
      have CBD stones at ERCP (P = 0.0295). In 28 patients with CBD stones remaining
      after ERCP, pre- rather than postoperative timing of ERCP prevented a potential
      second operation. The current success rate of 85% in clearing CBD stones at ERCP
      cannot support a routine policy of intraoperative cholangiography followed by
      postoperative ERCP.

PMID- 8540664
TI  - Parotid duct stenosis: interventional radiology to the rescue.
AB  - Recurrent parotid sialadenitis due to isolated parotid duct stenosis is an
      uncommon condition and poses a difficult management problem. Conventional
      surgical practice carries with it a potentially high morbidity for what is a
      benign condition. We present three cases where parotid duct stenosis has been
      treated by balloon dilatation and propose that this is a safe, quick and
      repeatable method for dealing with this problem.

PMID- 8540665
TI  - Randomised comparison of silicone versus Teflon cannulas for peripheral
      intravenous nutrition.
AB  - The use of peripheral intravenous nutrition using standard Teflon cannulas is
      limited by a high incidence of thrombophlebitis, with resultant frequent line
      changes and compromised nutritional therapy. Fine-bore silicone catheters may
      reduce the incidence of thrombophlebitis; we prospectively compared the silicone
      catheter with a Teflon cannula in a randomised trial. Seventy-nine surgical
      patients were randomised to receive peripheral nutrition (10 g nitrogen; 1770
      kcal; 650 mOsm/l) either via a Teflon cannula (18G, 4.4 cm long) or via a
      silicone catheter (23G, 15 cm long). Compared with the group randomised to a
      standard Teflon cannula, patients fed via a silicone catheter had a significant
      (P < 0.001) improvement in (a) median time to survival of the first catheter (125
      h vs 48 h); (b) incidence of catheter reinsertions (13% vs 75%); and (c)
      incidence of thrombophlebitis (10% vs 48%). Delivery of a moderately hypertonic
      nutritional solution through a fine-bore silicone catheter is safe, durable and
      well tolerated, with a low incidence of complications relative to a Teflon
      cannula. An expanded role for this catheter in nutritional therapy is feasible,
      which may reduce the requirement for central venous parenteral nutrition.

PMID- 8540666
TI  - Should all patients with ureteric colic be admitted?
AB  - A two-part study was undertaken to determine if all patients with uncomplicated
      ureteric colic require admission. The analgesic requirements and outcome in 31
      patients admitted with ureteric colic were assessed; 20/31 (64%) required no
      further analgesia after admission and 8/31 (26%) required only oral/rectal
      analgesia. In the second part of the study a protocol was introduced allowing
      patients with no complicating factors to be discharged directly from the A&E
      department. Of 58 patients seen in the A&E department, 29 were discharged for
      outpatient follow-up. Of these patients, 19 required no additional acute hospital
      treatment, five returned for further parenteral analgesia but outside the time
      they would have stayed in hospital under our previous protocol (ie beyond 48 h)
      and three returned within 48 h of their first attendance with pain which had not
      responded to oral analgesics. No patient discharged from A&E subsequently
      required intervention for obstruction or infection. We conclude that it is not
      necessary to admit patients with uncomplicated ureteric colic if the initial
      colic has been relieved and there is adequate social support.

PMID- 8540667
TI  - Blood transfusion requirements in femoral neck fractures.
AB  - Fractures of the femoral neck are common, and their incidence seems likely to
      increase. A prospective study in 1991 of 80 patients with such fractures
      suggested that not all need to be cross-matched preoperatively, a finding
      supported by the existing literature. At the same time, a survey of transfusion
      protocols in hospitals throughout the country suggested that much blood was being
      wasted daily in unnecessary cross-matching. This survey was repeated in 1995, and
      little appears to have changed. The implications of this are discussed.

PMID- 8540668
TI  - Benign breast surgery: is there a need for outpatient follow-up?
AB  - The majority of patients referred to a breast clinic will have benign disease
      (BBD) and, after appropriate assessment, most can be reassured and discharged.
      However, some patients will require excision biopsy to confirm the diagnosis. We
      have performed a prospective study to determine whether routine outpatient follow
      up of these patients can be safely omitted. A series of 100 consecutive patients
      undergoing breast biopsy for disease, assessed as benign in outpatients, were
      studied. Before discharge each was given an information sheet outlining their
      postoperative recovery and advised to see their general practitioner (GP) between
      the 7th and 10th postoperative day for wound check, suture removal and histology.
      Of the 100 women in the study group, 94 had benign histology. At the
      postoperative visit to the GP a full discharge summary including histology was
      available for 88 patients. In six patients there was a delay in discharge summary
      generation. Malignant or premalignant disease was found in six patients. All were
      safely identified and recalled for counselling and further treatment as
      appropriate. We believe that the routine follow-up of patients undergoing benign
      breast surgery can safely be avoided if there is a satisfactory protocol which is
      understood by both the patients and GPs.

PMID- 8540669
TI  - Crochet hooks in varicose vein surgery.

PMID- 8540670
TI  - Trephine colostomy: a warning.
AB  - A case of trephine colostomy is presented in which air insufflation incorrectly
      identified the distal limb. Disaster was averted by correct identification at
      laparotomy. The probable cause of the error and methods of avoidance are
      discussed.

PMID- 8540671
TI  - Peptic ulcers can now be cured without operation.

PMID- 8540672
TI  - The surgery of mitral stenosis 1898-1948: why did it take 50 years to establish
      mitral valvotomy?

PMID- 8540673
TI  - Use of split-skin grafting in the treatment of chronic leg ulcers.

PMID- 8540674
TI  - Use of split-skin grafting in the treatment of chronic leg ulcers.

PMID- 8540675
TI  - Inpatient and post-discharge wound infections in general surgery.

PMID- 8540676
TI  - Evaluation of vascular and metabolic deficiency in patients with large leg
      ulcers.

PMID- 8540677
TI  - A 5 year audit of outcome of apicectomies carried out in a district general
      hospital.

PMID- 8540678
TI  - Some clinical aspects of reconstruction for chronic anterior cruciate ligament
      deficiency.

PMID- 8540679
TI  - Tension-free mesh hernia repair: review of 1098 cases using local anaesthesia in
      a day unit.

PMID- 8540680
TI  - Tension-free mesh hernia repair: review of 1098 cases using local anaesthesia in
      a day unit.

PMID- 8540681
TI  - Pelvic abscess following laparoscopic appendicectomy.

PMID- 8540682
TI  - Pelvic abscess following laparoscopic appendicectomy.

PMID- 8540683
TI  - [Uniparental disomy: a review of causes and clinical sequelae].
AB  - 1) Uniparental disomy (UPD) results from the exceptional derivation of a pair of
      the offspring chromosome from one parent only and has been documented thus far
      for chromosomes 2, 4, 5, 6, 7, 11, 13, 14, 15, 20, 21, 22 both X's and the XY
      pair. Its consequences on the phenotype may result from three potentially harmful
      effects, namely isodisomy, interference with genomic imprinting and, occasionally
      the vestigial aneuploidy from which UPD may have originated. 2) In isodisomy, the
      uniparental pair is partially or entirely homozygous, through the duplication of
      a same chromosomal DNA template, thus bringing about an increased risk of
      recessive disorders. As a result, conditions such as cystic fibrosis, a type of
      osteogenesis imperfecta, thalassemia alpha or beta, retinoblastoma, rod
      monochromacy, etc., have now been reported. 3) Duplication of both homologues of
      a parental pair in a diploid genome is called heterodisomy. Both iso- and
      heterodisomy may also cause disruption of the genomic imprints normally modifying
      the differential expression of some maternal and paternal genes or gene sequences
      needed for eugenic growth and development, in the course of normal biparental
      inheritance. Such a disturbance can be one of the causes of congenital clinical
      entities as well defined as Angelman, Prader-Willi or Beckwith-Wiedemann
      syndromes and some new syndromes, for instance for UPD 7 mat, UPD 14 mat and,
      probably also 14 pat. 4) All in all, UPD can cause morbidity or lethality by
      altering imprinting processes, mimicking certain deletions or duplications,
      generating recessive disorders or prompting malignant tumor development. 5) In
      the clinical field, UPD occasionally upsets some mendelian tenets of traditional
      inheritance, and raises, the question of the evolutional role plaid by genomic
      imprinting (GI). An hypothetical opinion is that one of GI potential side effects
      is a biased intergenerational preferential display or skip of parental features.
      This could be so because some of the inherited genes or gene domains only gain
      maternal or paternal expression in the offspring, as a function of their parental
      imprint.

PMID- 8540684
TI  - Clinical dysmorphology beyond developmental genetics: recent advances in some
      human developmental genes.
AB  - Dysmorphology is involved in abnormal development, genetic causes and
      embryological development. The clinical studies of dysmorphic syndromes must lead
      to the identification and analysis of developmental genes involved in normal and
      abnormal morphogenesis. The identification of different genes from various gene
      families involved in dysmorphogenesis has recently emerged. The authors review
      the recent advances in some human developmental gene families (PAX, FGFR, BMP
      genes). These genes often act as patterning genes and as possible oncogenes; they
      are of interest for developmental biologists and for medical geneticists.

PMID- 8540685
TI  - Chromosome changes in lymphocytes of patients with scleroderma.
AB  - The authors have analyzed cytogenetically 28 cultured lymphocytes from females
      with Diffuse Scleroderma and 28 female controls between 30 and 70 years of age.
      Recurrent chromosome abnormalities were +8, +X, -X, and the PCD(X) phenomenon.
      Triplo X cells were significatively more frequent in patients than in controls.
      The incidence of +X and PCD(X) was significatively higher in the patients between
      30 and 50 years of age, while the frequency of -X cells was higher in controls
      than in patients. None of these chromosome changes was correlated with the
      presence of anticentromere antibodies (ACA) in the patients' serum. Random
      structural chromosome abnormalities were also observed in the patients, but no
      break point clustering was observed. The incidence of chromosome breaks was
      significatively higher in patients than in controls. These data suggest a general
      tendency of females with Scleroderma to develop X polisomies and +X and the
      PCD(X) phenomenon may be considered Scleroderma related in younger patients.

PMID- 8540686
TI  - Prenatal diagnosis of chromosomal aneuploidies by fluorescence in situ
      hybridization on uncultured amniotic cells: experience with 630 samples.
AB  - 612 amniotic fluid samples have been analyzed by an interphase FISH protocol in
      order to identify the X, Y, 13, 18 and 21 chromosomes in uncultured amniotic
      cells, parallel to conventional cytogenetic techniques. The aims were to value
      the interest and the feasibility of such technique in a regional prenatal
      diagnosis laboratory, and to estimate the assistance FISH can give in cases of
      supposed fetal mosaics and the importance of the reservations voiced by certain
      teams about FISH use when the fluid is hemorrhagic or about the employment of
      certain probes. The ten aneuploidies of the set, seven autosomal and three
      gonosomal, have been perfectly identified. Only one misdiagnosis has been
      reported, which clearly show the FISH limits: it was derived from a morphological
      rehandling in a chromosomal segment labeled by a probe. Regarding to the mosaics,
      the respective numbers of each cellular populations estimated by interphase FISH
      seems not to differ from those valued by the metaphase cytogenetic. Finally our
      results in hemorrhagic samples (64/612) seem not different than those obtained
      with clear samples.

PMID- 8540687
TI  - Genetic heterogeneity study of non-syndromic autosomal recessive sensorineural
      deafness within the Tunisian population.
AB  - The number of loci for non-syndromic autosomal recessive sensorineural (N-SARS)
      deafness, was estimated within the Tunisian population and compared to that
      obtained in other populations. 30 deaf couples have been collected from 4
      governorates (2,318,900 inhabitants) and 3 villages. Our investigations in these
      regions show that the percentage of congenitally deaf persons which marry each
      other is exceptionally low (10-30%). The number of loci for N-SARS deafness in
      the governorates sample was estimated at 8.3. Results could provide data for
      genetic counseling and facilitate our research concerning the localization of the
      different loci for N-SARS deafness present in Tunisian population.

PMID- 8540688
TI  - DiGeorge syndrome and partial monosomy 10p: case report and review.
AB  - DiGeorge syndrome (DGS) is predominantly caused by partial monosomy 22q11, but a
      subset of patients with DGS show deletions of 10p or other chromosomal
      abnormalities. The authors describe a 20 months old girl with DGS and a monosomy
      10p bringing the number of DGS patients with this chromosomal abnormality to
      nine. She has a monosomy 10p13-pter and a trisomy 10q26-qter due to a meiotic
      recombination of a maternal inversion (10) (p13q26). The proposita's phenotype
      demonstrates typical features of the del (10p) syndrome which include mental
      retardation, abnormally shaped skull, hypertelorism, low nasal bridge,
      micrognathia, dysmorphic low set ears, short neck, foot abnormalities, and
      cardiac defect. The diagnosis of DGS was made unequivocally within the first
      weeks of life because of the typical features-cardiac defect, hypoplastic thymus,
      T-cell defect, hypocalcemia, and hypoparathyroidism. The common DGS mutation
      microdeletion 22q11-was excluded by FISH analysis, and the breakpoints on
      chromosome 10 were mapped between D10S189 and D10S191 on the short arm and
      proximal to D10S25 on the long arm.

PMID- 8540689
TI  - [Translocation t(6;9;8)(p23;q34;q22) in acute myeloid leukemia: Contribution of
      fluorescence in situ hybridization].
AB  - A complex translocation involving chromosome 6, 8 and 9 [t(6;9;8)(p23;q34;q22)]
      associated with other structural and numerical abnormalities was observed on bone
      marrow karyotype of a woman suffering with acute myeloblastic leukemia (AML2).
      Fluorescence in situ hybridization agreed with the conventional cytogenetic
      interpretation by showing that a part of chromosome 6 short arm was inserted on
      the rearranged chromosome 9 resulting in the t (6;9) usually encountered in AML.

PMID- 8540690
TI  - Use of amphotericin B with azole antifungal drugs: what are we doing?

PMID- 8540691
TI  - Transglutaminase-catalyzed reaction is important for molting of Onchocerca
      volvulus third-stage larvae.
AB  - Highly insoluble proteins, which are probably cross-linked, are common in the
      cuticle and epicuticle of filarial parasites and other nematode species. We have
      investigated the possible involvement of transglutaminase (TGase)-catalyzed
      reactions in the development of Onchocerca volvulus fourth-stage larvae (L4) by
      testing the effects of TGase inhibitors on the survival of third-stage larvae
      (L3) and the molting of L3 to L4 in vitro. The larvae were cultured in the
      presence of three specific TGase inhibitors: monodansylcadaverine, cystamine, and
      N-benzyloxycarbonyl-D,L-beta-(3-bromo-4,5-dihydroisoxazol-5-yl)-al anine
      benzylamide. None of the inhibitors reduced the viability of either L3 or L4.
      However, the inhibitors reduced, in a time- and dose-dependent manner, the number
      of L3 that molted to L4 in vitro. Molting was completely inhibited in the
      presence of 100 to 200 microM inhibitors. Ultrastructural examination of L3 that
      did not molt in the presence of monodansylcadaverine or cystamine indicated that
      the new L4 cuticle was synthesized, but there was an incomplete separation
      between the L3 cuticle and the L4 epicuticle. The product of the TGase-catalyzed
      reaction was localized in molting L3 to cuticle regions where the separation
      between the old and new cuticles occurs and in the amphids of L3 by a monoclonal
      antibody that reacts specifically with the isopeptide epsilon-(gamma
      glutamyl)lysine. These studies suggest that molting and successful development of
      L4 also depends on TGase-catalyzed reactions.

PMID- 8540692
TI  - Cloning and characterization of a novel, plasmid-encoded trimethoprim-resistant
      dihydrofolate reductase from Staphylococcus haemolyticus MUR313.
AB  - In recent years resistance to the antibacterial agent trimethoprim (Tmp) has
      become more widespread, and several trimethoprim-resistant (Tmpr) dihydrofolate
      reductases (DHFRs) have been described from gram-negative bacteria. In
      staphylococci, only one Tmpr DHFR has been described, the type S1 DHFR, which is
      encoded by the dfrA gene found on transposon Tn4003. In order to investigate the
      coincidence of high-level Tmp resistance and the presence of dfrA, we analyzed
      the DNAs from various Tmpr staphylococci for the presence of dfrA sequences by
      PCR with primers specific for the thyE-dfrA genes from Tn4003. We found that 30
      or 33 isolates highly resistant to Tmp (MICs, > or = 512 micrograms/ml) contained
      dfrA sequences, whereas among the Tmpr (MICs, < or = 256 micrograms/ml) and Tmps
      isolates only the Staphylococcus epidermidis isolates (both Tmpr and Tmps) seemed
      to contain the dfrA gene. Furthermore, we have cloned and characterized a novel,
      plasmid-encoded Tmpr DHFR from Staphylococcus haemolyticus MUR313. The dfrD gene
      of plasmid pABU17 is preceded by two putative Shine-Dalgarno sequences
      potentially allowing for the start of translation at two triplets separated by
      nine nucleotides. The predicted protein of 166 amino acids, designated S2DHFR,
      encoded by the longer open reading frame was overproduced in Escherichia coli,
      purified, and characterized. The molecular size of the recombinant S2DHFR was
      determined by ion spray mass spectrometry to be 19,821.2 +/- 2 Da, which is in
      agreement with the theoretical value of 19,822 Da. In addition, the recombinant
      S2DHFR was shown to exhibit DHFR activity and to be highly resistant to Tmp.

PMID- 8540693
TI  - SB 205952, a novel semisynthetic monic acid analog with at least two modes of
      action.
AB  - The biological properties of SB 205952, a nitrofuryl oxazole derivative of monic
      acid, differ from those of the closely related antibacterial agent mupirocin.
      Compared with mupirocin, SB 205952 has increased antimicrobial potency, an
      extended spectrum including mupirocin-resistant staphylococci, and rapid
      bactericidal activity. SB 205952, like mupirocin, is a potent inhibitor of
      bacterial isoleucyl-tRNA synthetase (IRS) in mupirocin-susceptible organisms but
      does not inhibit IRS from mupirocin-resistant staphylococci, indicating that SB
      205952 has more than one mechanism of action. SB 205952 rapidly inhibits protein,
      RNA, and DNA syntheses in mupirocin-susceptible and mupirocin-resistant
      staphylococci. In each case, the effect on RNA synthesis is relaxed by treatment
      with chloramphenicol, indicating that inhibition of RNA synthesis is probably a
      secondary consequence of stringent control. It is proposed that SB 205952
      possesses one or more mechanisms of action in addition to IRS inhibition,
      probably mediated by its nitrofuryl component.

PMID- 8540694
TI  - Sterol compositions and susceptibilities to amphotericin B of environmental
      Cryptococcus neoformans isolates are changed by murine passage.
AB  - Previous studies have shown that sequential isolates from patients with
      persistent Cryptococcus neoformans meningoencephalitis can vary in sterol
      composition and susceptibility to antifungal drugs. To investigate the potential
      of host factors as mediators of this phenomenon, we compared fungal
      susceptibilities of environmental and clinical isolates from a limited geographic
      area. Clinical isolates were less susceptible to amphotericin B than
      environmental isolates. Five environmental isolates were passaged through BALB/c
      murine hosts; the passaged isolates had changes in sterol composition and reduced
      amphotericin B susceptibilities relative to those of the parent isolates. In
      contrast, murine passage of these isolates did not alter their susceptibilities
      to fluconazole. The results confirm that changes in sterol composition and
      antifungal susceptibility can occur in vivo as a result of host factors and
      suggest that human infection can result in selection of variants with reduced
      susceptibilities to amphotericin B.

PMID- 8540695
TI  - In vivo efficacy of azithromycin in treatment of systemic infection and septic
      arthritis induced by type IV group B Streptococcus strains in mice: comparative
      study with erythromycin and penicillin G.
AB  - We compared the activities of azithromycin, erythromycin, and penicillin G in a
      mouse model of systemic infection and septic arthritis induced by type IV group B
      streptococci (GBS). The in vitro and in vivo efficacy data for these drugs were
      analyzed relative to the pharmacokinetics of the drugs in sera, joints, and
      kidneys. Adult CD-1 mice were infected intravenously with 10(7) CFU of type IV
      GBS. Intraperitoneal drug administration was initiated with different dose
      regimens at different times after infection. A single dose of azithromycin (100
      mg/kg) strongly reduced the incidence of articular lesions with respect to that
      with erythromycin or penicillin G. Treatment with azithromycin (three
      intraperitoneal administrations of 50 mg/kg at 12-h intervals) resulted in the
      complete prevention of arthritis. In contrast, erythromycin was poorly effective
      and penicillin G was effective only if inoculated 30 min after infection and at
      high doses (400,000 or 600,000 IU/kg). Furthermore, azithromycin was able to cure
      about 70% of the mice when administered 7, 8, and 9 days after GBS infection.
      Azithromycin was much more active than erythromycin and penicillin G with respect
      to bacterial killing in the joints and kidneys. In fact, cultures from these
      tissues were always negative no matter what treatment schedule was employed. The
      pharmacokinetics of azithromycin account for its superior in vivo efficacy
      against type IV GBS. A longer half-life and higher levels of this drug in serum
      and tissues with respect to those for erythromycin or penicillin G were achieved.
      The high affinity of azithromycin for the joints strongly supports its potential
      value for therapy of septic arthritis, which is a severe and frequent clinical
      manifestation of GBS infection.

PMID- 8540696
TI  - Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa.
AB  - We have earlier described mexA-mexB-oprK, an operon involved in pyoverdine export
      in Pseudomonas aeruginosa, and suggested that the products of these genes also
      contribute to the active efflux of several antibiotics (K. Poole, K. Krebes, C.
      McNally, and S. Neshat, J. Bacteriol. 175:7363-7372, 1993). Recently the outer
      membrane component of this efflux system was shown to be OprM, rather than OprK
      (N. Gotoh and K. Poole, unpublished results). In the present study, the
      conclusion concerning the efflux activity of this system was confirmed and
      extended by the measurement of drug accumulation in intact cells. Thus, the
      steady-state accumulation levels of tetracycline and norfloxacin were increased
      in mexA and oprM null mutants. mexA and oprM null mutants also showed an increase
      in susceptibility to a wide variety of beta-lactam antibiotics and an increase in
      the steady-state accumulation level of benzylpenicillin, indicating that the MexA
      MexB-OprM pump also effluxes beta-lactams. Furthermore, deenergization of the
      cytoplasmic membrane with a proton conductor always produced a strong increase in
      the accumulation level. Finally, a single-step mutant over-producing MexAB-OprM
      accumulated less tetracycline and chloramphenicol than the parent strain and was
      more resistant to a wide range of antimicrobial compounds, including beta
      lactams. These results support the notion that these proteins contribute to the
      intrinsic resistance of P. aeruginosa through the multidrug active efflux
      process.

PMID- 8540697
TI  - Amphotericin B liposomes with prolonged circulation in blood: in vitro antifungal
      activity, toxicity, and efficacy in systemic candidiasis in leukopenic mice.
AB  - Pegylated amphotericin B (AmB) liposomes (PEG-AmB-LIP) were compared with
      laboratory-prepared nonpegylated AmB liposomes (AmB-LIP), a formulation with a
      lipid composition the same as that in AmBisome, as well as with industrially
      prepared AmBisome regarding their in vitro antifungal activities, toxicities,
      blood residence times, and therapeutic efficacies. Killing of Candida albicans (>
      99.9%) during short-term (6-h) incubation was observed at 0.2 mg of AmB per liter
      for AmB desoxycholate, 0.4 mg of AmB per liter for PEG-AmB-LIP, 0.8 mg of AmB per
      liter for AmB-LIP, and 12.8 mg of AmB per liter for AmBisome. The maximum
      tolerated doses of PEG-AmB-LIP, AmB-LIP, and AmBisome were 15, 19, and > 31 mg of
      AmB per kg of body weight, respectively. In contrast to AmB-LIP, the blood
      residence time of PEG-AmB-LIP was prolonged and dose independent. In a model of
      systemic candidiasis in leukopenic mice at a dose of 5 mg of AmB per kg, PEG-AmB
      LIP was completely effective and AmB-LIP was partially effective, whereas
      AmBisome was not effective. AmB-LIP at 11 mg of AmB per kg was partially
      effective. AmBisome at 29 mg of AmB per kg was completely effective. In
      conclusion, the therapeutic efficacies of AmB liposomes can be improved by
      preparing AmB liposomes in which a substantial reduction in toxicity is achieved
      while antifungal activity is retained. In addition, therapeutic efficacy is
      favored by a prolonged residence time of AmB liposomes in blood.

PMID- 8540698
TI  - Relevance of Chlamydia pneumoniae murine pneumonitis model to evaluation of
      antimicrobial agents.
AB  - A mouse model of Chlamydia pneumoniae pneumonitis was established in outbred MF1
      mice immunosuppressed with cyclophosphamide. Following intranasal inoculation
      with 2.2 x 10(3) inclusion-forming units of C. pneumoniae TW-183 per mouse,
      chlamydiae were culturable from the lungs for at least 29 days. Progressive
      subacute pneumonitis with perivascular and peribronchial lymphoid cell
      hyperplasia was observed, and C. pneumoniae organisms were located in
      consolidated areas of tissue by immunocytochemistry. Mice were treated orally,
      commencing at 8 days after infection, with clinically achievable concentrations
      of amoxicillin-clavulanate or ciprofloxacin (three times daily for 7 days),
      ofloxacin, doxycycline, or erythromycin (twice daily for 7 days), or azithromycin
      (once daily for 4 days). Despite disparate antichlamydial activity in cell
      culture and different pharmacokinetic properties in infected animals, all
      treatments reduced the chlamydial load in the lungs (P < 0.05) when the loads
      were evaluated by culture at 1 and 10 days after the cessation of dosing, and
      this was reflected in the histopathological and immunocytochemistry scores. There
      was no significant difference between these treatments, and C. pneumoniae TW-183
      was eradicated from the majority but not from all mice. These results confirm the
      limited clinical data available to date. In conclusion, a range of oral
      antimicrobial agents commonly used for the treatment of community-acquired
      respiratory infection was found to be efficacious in this experimental model of
      C. pneumoniae pneumonitis, which may therefore be of utility in chemotherapy and
      follow-up studies.

PMID- 8540699
TI  - Bactericidal properties of Campylobacter jejuni-specific immunoglobulin M
      antibodies in commercial immunoglobulin preparations.
AB  - Campylobacter jejuni is one of the most common enterocolitis-causing
      microorganisms worldwide. It is of particular importance in immunodeficient
      patients, who frequently are prone to develop extraintestinal manifestations.
      Since these cases respond poorly to antibiotic treatment, a supportive
      immunomodulating therapy including the administration of C. jejuni-specific
      immunoglobulins would be desirable. In the present study, nine commercial
      immunoglobulin preparations for intravenous use were tested for the presence of
      C. jejuni lipopolysaccharide (LPS)- and outer membrane protein (OMP)-specific
      antibodies by using immunoblot and enzyme-linked immunosorbent assay techniques.
      The immunoglobulin G (IgG) antibody reactivities against these antigens were
      comparable in eight of nine tested immunoglobulin preparations. Only in one
      preparation were C. jejuni OMP- and LPS-specific IgM antibodies found. In this
      preparation the immunoblot test revealed a strong reactivity against both
      flagellin and a major OMP. Moreover, all immunoglobulin preparations recognized
      OMPs of C. jejuni serotypes Lior 4, 9, 11, and 29 equally strongly, while the
      reactivity to an anti-Lior 36 isolate was less marked. Furthermore, the
      bactericidal properties of three immunoglobulin preparations were tested by means
      of chemiluminescence signaling in and bacterial killing by human
      polymorphonuclear leukocytes (PMNL). The results show that the IgM preparation
      enhanced Campylobacter-triggered chemiluminescence signaling in PMNL as well as
      killing of C. jejuni by PMNL, while the other immunoglobulin preparations did not
      do so. These results suggest that the administration of immunoglobulin
      preparations containing C. jejuni-specific IgM antibodies would be beneficial for
      patients with severe C. jejuni infections.

PMID- 8540700
TI  - DNA gyrase gyrA mutations in quinolone-resistant clinical isolates of Pseudomonas
      aeruginosa.
AB  - The mutations in the quinolone resistance-determining region of the gyrA gene
      from clinical isolates of Pseudomonas aeruginosa were determined by DNA
      sequencing. The strains were isolated in 1989 and 1993. No mutations were
      detected in the clinical isolates in 1989, while five types of mutations were
      identified in the isolates in 1993. These mutations were as follows: group 1, a
      Thr residue to an Ile residue at position 83 (Thr-83-Ile); group 2, Asp-87-Asn;
      group 3, Thr-83-Ile and Asp-87-Gly; group 4, Thr-83-Ile and Asp-87-Asn; group 5,
      Thr-83-Ile and Asp-87-His. Three types of double mutations (groups 3, 4, and 5)
      have not been described previously. These mutations were homologous to the Ser-83
      Leu, Asp-87-Asn, and Asp-87-Gly changes observed in Escherichia coli. Thus, DNA
      gyrase A subunit mutations are implicated in resistance to quinolones in P.
      aeruginosa as well as E. coli.

PMID- 8540701
TI  - Liposomal encapsulation of foscarnet protects against hypocalcemia induced by
      free foscarnet.
AB  - Hypocalcemia and an increase in creatinine level are the most important serious
      effects associated with foscarnet (PFA) therapy. In an animal model, we have
      explored the potential protective role of liposome-encapsulated foscarnet (LE
      PFA) on these metabolic abnormalities. PFA administered as one bolus injection
      (0.5 or 1.0 g/kg) caused significant rapid decreases (approximately 20%) in the
      levels of calcium and phosphorus in serum within a few minutes and up to 30 min
      after injection. LE-PFA did not induce any of these changes, while peak levels in
      serum and the half-life of this formulation were much higher than those of the
      free drug. PFA administered for 2 weeks (340 or 500 mg/kg/day) resulted in no
      changes in creatinine or blood urea nitrogen levels in serum at the low-dosage
      level, but at the higher-dosage level, the creatinine level in serum increased by
      day 5 posttreatment. Furthermore, there was no increase in the creatinine or
      blood urea nitrogen level after 2 weeks of treatment with LE-PFA at a dosage of
      35 mg/kg/day. When the pharmacokinetics of both free PFA and LE-PFA were
      compared, the plasma half-life of the encapsulated drug was approximately four
      times longer than that of the free drug. In addition, the systemic clearance of
      LE-PFA was approximately one-fifth of that of the free drug. In conclusion, free
      PFA causes hypocalcemia and hypophosphatemia and increases the creatinine level
      in serum, whereas the LE form of this drug seems to protect against the abnormal
      changes in calcium and phosphorus levels caused by the free drug. By preventing
      hypocalcemia and increasing its half-life, LE-PFA can be used at lower doses and
      at longer intervals. Clinical investigations of these formulations may be
      worthwhile.

PMID- 8540702
TI  - Effect of levofloxacin on glycosaminoglycan and DNA synthesis of cultured rabbit
      chondrocytes at concentrations inducing cartilage lesions in vivo.
AB  - We investigated the toxic effect of levofloxacin (LVFX), a quinolone
      antibacterial agent, on cartilage by examining aspects of its in vivo
      toxicokinetics and effect on the function of cultured chondrocytes of the femoral
      articular cartilage from juvenile New Zealand White rabbits. Repeated
      administration of LVFX (100 mg/kg) orally for 7 days induced focal necrosis and
      superficial erosion in the articular cartilage of the femoral condyle, but 30
      mg/kg did not. Concentrations of LVFX in the cartilage were highest at the first
      sampling point (30 min) after a single administration, being 4.93 and 12.2
      micrograms/g in the 30- and 100-mg/kg groups, respectively. The arthropathic
      concentration of LVFX in the cartilage was then shown to be 12.2 micrograms/g or
      more. For an in vitro study, chondrocytes were separated from the articular
      cartilage of the rabbit femoral condyle and cultured for 7 days until confluence.
      35SO4 uptake by cultured chondrocyte sheets was most susceptible to LVFX,
      decreasing at drug concentrations of 5 micrograms/ml or more in 24- and 48-h
      cultures but not in a 72-h culture. Furthermore, 3H-thymidine uptake was
      decreased at concentrations of 10 micrograms/ml or more in a 48-h culture but not
      in 24- and 72-h cultures. Rhodamine 123 accumulation was susceptible to
      inhibition in cultured chondrocytes at an LVFX concentration of 10 micrograms/ml
      or more. These results suggest that LVFX inhibits glycosaminoglycan synthesis
      initially and DNA synthesis and mitochondrial function secondarily at actual
      arthropathic concentrations in cultured rabbit chondrocytes but that these
      changes are reversible and not enough to kill the cells.

PMID- 8540703
TI  - Synergistic effect of amoxicillin and cefotaxime against Enterococcus faecalis.
AB  - The antibacterial efficacy of the combination of amoxicillin and cefotaxime was
      assessed against 50 clinical strains of Enterococcus faecalis. For 48 of 50
      strains, the MIC of amoxicillin that inhibited 50% of isolates tested decreased
      from 0.5 microgram/ml (range, 0.25 to 1 microgram/ml) to 0.06 microgram/ml
      (range, 0.01 to 0.25 microgram/ml) in the presence of only 4 micrograms of
      cefotaxime per ml. Alternatively, the MIC of cefotaxime that inhibited 50% of
      isolates tested decreased from 256 micrograms/ml (range, 8 to 512 micrograms/ml)
      to 1 micrograms/ml (range, 0.5 to 16 micrograms/ml) in the presence of only 0.06
      microgram of amoxicillin per ml. For JH2-2, a reference strain of E. faecalis,
      the MICs of amoxicillin, cefotaxime, and amoxicillin in the presence of
      cefotaxime (4 micrograms/ml) were 0.5, 512, and 0.06 microgram/ml, respectively.
      By using a penicillin-binding protein (PBP) competition assay, it was shown that
      with cefotaxime, 50% saturation of PBPs 2 and 3 was obtained at very low
      concentrations (< 1 microgram/ml), while 50% saturation of PBPs 1, 4, and 5 was
      obtained with > or = 128 micrograms/ml. With amoxicillin, 50% saturation of PBPs
      4 and 5 was obtained at 0.12 and 0.5 microgram/ml, respectively. Therefore, the
      partial saturation of PBPs 4 and 5 by amoxicillin combined with the total
      saturation of PBPs 2 and 3 by cefotaxime could be responsible for the observed
      synergy between these two compounds.

PMID- 8540704
TI  - Bactericidal activity against cephalosporin-resistant Streptococcus pneumoniae in
      cerebrospinal fluid of children with acute bacterial meningitis.
AB  - There are reports of failure of extended-spectrum cephalosporin treatment in
      pneumococcal meningitis. On the basis of in vitro and animal experimental
      studies, the addition of vancomycin or rifampin to an extended-spectrum
      cephalosporin has been recommended for empiric treatment of these patients.
      Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis
      randomized to receive ceftriaxone alone (n = 11), ceftriaxone plus rifampin (n =
      10), or ceftriaxone plus vancomycin (n = 10). The CSF from children receiving
      ceftriaxone alone was unable to kill intermediately ceftriaxone-resistant or
      fully resistant strains when the concentration of ceftriaxone in the CSF was less
      than 5 micrograms/ml. At higher concentrations bactericidal activity was present.
      We have shown that vancomycin penetrates reliably into the CSF of children with
      acute meningitis, which is in contrast to previous studies with adults. The
      addition of vancomycin or rifampin to ceftriaxone resulted in significantly
      enhanced CSF bactericidal activity compared with that of ceftriaxone alone
      against these resistant strains. Our data suggest that the addition of rifampin
      or vancomycin to ceftriaxone may be useful for the treatment of cephalosporin
      resistant pneumococcal meningitis.

PMID- 8540705
TI  - Antiviral, metabolic, and pharmacokinetic properties of the isomeric
      dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol.
AB  - 4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA) is the most
      antivirally active member of a novel class of optically active isomeric
      dideoxynucleosides in which the base has been transposed from the natural 1'
      position to the 2' position and the absolute configuration is (S,S). IsoddA was
      active against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2
      (strain ZY), and HIV-1 clinical isolates. Combinations of the compound with
      zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or 5-fluoro-2'
      deoxy-3'-thiacytidine showed synergistic inhibition of HIV. A moderate reduction
      of activity was observed with clinical isolates resistant to zidovudine. An
      IsoddA-resistant virus (eightfold-increased 50% inhibitory concentration) was
      selected in vitro by repeated passage of HIV-1 (HXB2) in the presence of
      increasing concentrations of IsoddA. The reverse transcriptase-coding region of
      the mutant virus contained a single base change resulting in a change at codon
      184 from Met to Val. IsoddA was also active against hepatitis B virus (HBV) in
      vitro; however, it lacked substantial selective activity in an in vivo HBV model.
      IsoddA was inefficiently phosphorylated in CEM cells; however, the half-life of
      the triphosphate was 9.4 h, and IsoddATP was a potent inhibitor of HIV-1 reverse
      transcriptase, with a Ki of 16 nM. The cytotoxicity 50% inhibitory concentrations
      of IsoddA were greater than 100 microM for CEM, MOLT-4, IM9, and the HepG2
      derived HBV-infected 2.2.15 (subclone P5A) cell lines but were 12 and 11 microM
      for human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8540707
TI  - Foscarnet alters antidiuretic hormone-mediated transport.
AB  - Therapy with foscarnet is associated with acute renal failure. Prior studies have
      emphasized foscarnet's proximal tubular toxicity, but there have been isolated
      reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate
      analog, foscarnet is a competitive inhibitor of NaPO4 cotransport. However,
      foscarnet's effect on antidiuretic hormone (ADH)-induced transport has not been
      previously investigated. We studied foscarnet's modulation of transport in the
      toad urinary bladder. Foscarnet at 10 microM to 10 mM did not alter basal water
      or urea flux. Urea transport induced by a maximal dose of ADH (24 mIU/ml) was
      inhibited by 0.1 to 5.0 mM foscarnet. In tissues challenged with 0.5 to 1.0 mIU
      of ADH per ml, 1.0 to 10 mM foscarnet increased water flow but did not alter urea
      flux. Foscarnet also increased water flow induced by 1.0 to 10 microM forskolin.
      In tissues pretreated with 10 microM naproxen, foscarnet did not alter water flow
      induced by 0.5 to 1.0 mIU of ADH per ml or forskolin. These results indicate that
      foscarnet stimulates water flow induced by 0.5 to 1.0 mIU of ADH per ml at a site
      proximal to that of the generation of cyclic AMP and inhibits urea flux induced
      by a maximal dose of ADH at a separate site. In humans, foscarnet nephrotoxicity
      is likely not limited to the proximal nephron, but extends to the collecting
      duct. Patients receiving foscarnet should be closely monitored for disorders of
      urinary concentration.

PMID- 8540706
TI  - Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J
      derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase.
AB  - Halogenated gomisin J (a derivative of lignan compound), represented by the
      bromine derivative 1506 [(6R, 7S, S-biar)-4,9-dibromo-3,10-dihydroxy-1,2,11,12
      tetramethoxy-6, 7-dimethyl-5,6,7,8- tetrahydrodibenzo[a,c]cyclo-octene], was
      found to be a potent inhibitor of the cytopathic effects of human
      immunodeficiency virus type 1 (HIV-1) on MT-4 human T cells (50% effective dose,
      0.1 to 0.5 microM). Gomisin J derivatives were active in preventing p24
      production from acutely HIV-1-infected H9 cells. The selective indices (toxic
      dose/effective dose) of these compounds were as high as > 300 in some systems.
      1506 was active against 3'-azido-3'-deoxythymidine-resistant HIV-1 and acted
      synergistically with AZT and 2',3'-ddC. 1506 inhibited HIV-1 reverse
      transcriptase (RT) in vitro but not HIV-1 protease. From the time-of-addition
      experiment, 1506 was found to inhibit the early phase of the HIV life cycle. A
      1506-resistant HIV mutant was selected and shown to possess a mutation within the
      RT-coding region (at position 188 [Tyr to Leu]). The mutant RT expressed in
      Escherichia coli was resistant to 1506 in the in vitro RT assay. Some of the HIV
      strains resistant to other nonnucleoside HIV-1 RT inhibitors were also resistant
      to 1506. Comparison of various gomisin J derivatives with gomisin J showed that
      iodine, bromine, and chlorine in the fourth and ninth positions increased RT
      inhibitory activity as well as cytoprotective activity.

PMID- 8540708
TI  - Magnesium deficiency induces joint cartilage lesions in juvenile rats which are
      identical to quinolone-induced arthropathy.
AB  - Quinolones accumulate in cartilage, and because they form chelate complexes with
      divalent cations, they possess the potential to induce a deficiency of
      functionally available magnesium. To test the hypothesis that quinolone-induced
      arthropathy is caused (or aggravated) by magnesium deficiency in cartilage, we
      induced magnesium deficiency by feeding juvenile rats a magnesium-deficient diet
      for 9 days and treated the rats with single oral doses of ofloxacin (0, 100, 300,
      600, or 1,200 mg/kg of body weight) during this period. Additional groups of
      juvenile rats on a normal diet were treated with ofloxacin correspondingly.
      Typical cartilage lesions (e.g., swollen matrix, cleft formation) were found in
      knee joints of all magnesium-deficient rats, including those without ofloxacin
      treatment. Lesions in these groups were not distinguishable from lesions induced
      by a single dose of 600 mg of ofloxacin per kg of body weight or higher in rats
      on a normal diet. Ofloxacin levels in plasma after 600 mg/kg of body weight were
      approximately 10-fold higher than those in humans during therapy with this
      quinolone. Lesions in rats treated with ofloxacin plus magnesium deficiency were
      more pronounced than those in rats with normal magnesium concentrations. After
      intake of a magnesium-deficient diet for 9 days, the magnesium concentration in
      serum (mean +/- standard deviation) was 0.18 +/- 0.05 mmol/liter (control on
      normal diet, 0.82 +/- 0.10 mmol/liter). Magnesium concentrations in bone (femur)
      and cartilage (processus xiphoideus) samples were 64.7 +/- 10.5 and 14.3 +/- 3.9
      mmol/kg of dry weight, respectively, which corresponded to approximately 50% of
      the concentrations measured in controls on a normal diet. It was concluded that
      quinolone-induced arthropathy is probably caused by a deficit of available
      magnesium in joint cartilage due to the formation of quinolone-magnesium chelate
      complexes. If juvenile patients must be treated with quinolones for serious
      infections, it seems prudent to ensure that these patients do not have a
      disturbed magnesium balance.

PMID- 8540710
TI  - Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat
      model of Pneumocystis carinii pneumonia.
AB  - The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal
      models of Pneumocystis carinii pneumonia (PCP), with effective daily
      intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body
      weight-1 in mouse and rat models, respectively. Continuous infusion produced a
      moderately improved response in a rat model. The data reported here demonstrate
      that the response achieved by continuous infusion of 195 and 335 mg of DFO
      mesylate kg-1 day-1 in the rat model is associated with mean concentrations in
      plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung
      tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since
      current clinical use of DFO mesylate for the treatment of iron overload produces
      higher concentrations in the plasma of patients, DFO may prove to be a useful
      anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in
      lung tissue compared with that observed in plasma may be important in the
      response of PCP to DFO.

PMID- 8540709
TI  - Evidence for an efflux pump in multidrug-resistant Campylobacter jejuni.
AB  - Mechanisms of drug resistance in Campylobacter jejuni were investigated. Mutant
      strains 34PEFr, which was resistant to pefloxacin (128-fold increase in the MIC),
      and 34CTXr, which was resistant to cefotaxime (32-fold increase in the MIC) and
      which was derived from the susceptible parent 34s, were obtained by serial
      passages on pefloxacin and cefotaxime gradient plates, respectively. Both mutants
      showed cross-resistance to erythromycin, chloramphenicol, tetracycline, beta
      lactams, and quinolones. While the quinolone resistance of strain PEFr could be
      explained by a mutation at codon 86 of the gyrA gene, the multidrug resistance
      phenotype of both strains was further investigated. Accumulation of pefloxacin,
      ciprofloxacin, and minocycline was measured by fluorometry and was found to be
      lower in the mutant strains than in the parent strain. Preincubation of the cells
      with carbonyl cyanide m-chlorophenylhydrazone, however, completely abolished this
      difference. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      of outer membrane preparations from both mutant strains showed overexpression of
      two proteins of 55 and 39 kDa which were absent from the outer membranes of the
      wild-type strain. These results indicate that in C. jejuni 34PEFr and 34CTXr,
      multidrug resistance is associated with an efflux system with a broad
      specificity.

PMID- 8540711
TI  - Diversity among the gram-positive acetyltransferases inactivating streptogramin A
      and structurally related compounds and characterization of a new staphylococcal
      determinant, vatB.
AB  - A gene encoding an acetyltransferase inactivating streptogramin A (SgA) and
      structurally similar compounds was isolated from a staphylococcal plasmid and
      sequenced. This gene, designated vatB, potentially encodes a 212-amino-acid
      protein, VatB, of 23,320 Da with 47.4 and 58.4% amino acid identities with two
      other enzymes with the same activity, Vat and SatA, respectively, which are
      encoded by a staphylococcal plasmid and an enterococcal plasmid, respectively.
      The C-terminal parts of these three enzymes share significant homology with the C
      terminal parts of 10 other acetyltransferases modifying various substrates. A
      pair of degenerate primers representing the conserved motifs shared by VatB, Vat,
      and SatA was designed to detect the three genes encoding these SgA
      acetyltransferases. Five of 12 clinical SgAr Staphylococcus aureus isolates
      tested carried neither these genes nor the gene vga, which confers resistance to
      SgA by a different mechanism, suggesting that another gene(s) and possibly
      another mechanism of resistance to SgA in staphylococci remains to be
      characterized.

PMID- 8540712
TI  - Pharmacokinetics of cefodizime following single doses of 0.5, 1.0, 2.0, and 3.0
      grams administered intravenously to healthy volunteers.
AB  - Cefodizime is a new expanded-spectrum cephalosporin for parenteral use which
      possesses a broad antibacterial spectrum and potent antibacterial activity and is
      stable against most beta-lactamases. The aim of this study was to assess the
      pharmacokinetics of cefodizime, administered intravenously, over the dose range
      of 0.5 to 3.0 g in healthy volunteers. Concentrations of cefodizime in the serum
      and urine were determined by high-performance liquid chromatography. The area
      under the concentration-time curve from 0 h to infinity and the amount of drug
      excreted in urine from 0 to 34 h increased in a linear, dose-dependent manner
      with increasing doses of antibiotic from 0.5 to 3.0 g. Mean concentrations of
      cefodizime in plasma at the end of infusion increased from 97 to 440 mg liter-1
      over the dose range 0.5 to 3.0 g and displayed a slight deviation from linearity
      at doses in excess of 2.0 g. Total plasma clearance (3.11 liters h-1), volume of
      distribution at steady state (10.5 liters), terminal elimination half-life (3.3
      h), and renal clearance (1.91 liters h-1) remained constant over the doses
      administered. Cefodizime was well tolerated in this study.

PMID- 8540713
TI  - Population pharmacokinetics and renal function-sparing effects of amphotericin B
      colloidal dispersion in patients receiving bone marrow transplants.
AB  - The purpose of this study was to evaluate the pharmacokinetics of amphotericin B
      colloidal dispersion and its effect on creatinine clearance in bone marrow
      transplant patients with systemic fungal infections. Seventy-five patients (42
      females and 33 males) with a median age of 34.5 years and a median weight of 70.0
      kg were enrolled in the study. Patients received 1 of 15 dose levels (range, 0.5
      to 8.0 mg/kg of body weight) daily for a mean duration of 28 days and a mean
      cumulative dose amount of 8 g. Plasma samples for amphotericin B determination
      (median number, 4; range, 2 to 30) and daily serum creatinine values were
      obtained for each patient. Iterative two-stage analysis, one of several
      approaches to population pharmacokinetic and pharmacodynamic modelling, was
      employed for the pharmacokinetic analysis. The plasma data were available for 51
      of 75 patients and were best described by a two-compartment model. Both plasma
      clearance and volume of distribution increased with escalating doses; the overall
      average terminal elimination half-life was 29 h. Of the covariates studied, only
      body weight and dose size were significant. Serum creatinine values over the
      duration of therapy were available for 59 of 75 patients. Overall, there was no
      net change in renal function over the duration of therapy; 12 patients had > 30%
      increases in creatinine clearance, whereas 13 had > 30% decreases. No measure of
      amphotericin B colloidal dispersion exposure, demographic values, or concomitant
      treatment with other medications was related to changes in the creatinine
      clearance.

PMID- 8540714
TI  - Once-daily versus twice-daily administration of ceftazidime in the preterm
      infant.
AB  - Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to
      31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia
      were randomized on day 1 of life in two groups. One group (n = 13) was
      administered 25 mg of ceftazidime per kg of body weight once daily, and the other
      (n = 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also
      received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on
      day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an
      intravenous bolus injection. An additional blood sample was taken at 24 h from
      the group dosed once a day. High-performance liquid chromatography was used to
      determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime
      were best described by using a one-compartment model. The half-life for the
      elimination of the drug from serum, apparent volume of distribution, total body
      clearance of ceftazidime, and inulin clearance were not significantly different
      for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups.
      However, trough concentrations in serum for the twice-daily group were
      significantly (P < 0.001) higher (42.0 +/- 13.4 mg/liter) than those for the once
      daily group (13.1 +/- 4.7 mg/liter). The latter concentrations were all still
      substantially higher than the MIC of ceftazidime for major neonatal pathogens. We
      conclude that the currently recommended dosage of 25 mg of ceftazidime per kg
      twice daily for preterm infants with gestational ages below 32 weeks may be
      adjusted during the first days of life to one daily dose at 25 mg/kg, provided
      that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also
      given twice daily.

PMID- 8540715
TI  - Antifungal susceptibility testing of yeasts: evaluation of technical variables
      for test automation.
AB  - The technical parameters for antifungal susceptibility testing with Candida
      species were reexamined to determine the optimal conditions for testing with
      semiautomated preparations of broth microdilution cultures, automated
      spectrophotometric readings of the cultures, and dose-response and endpoint
      determinations by means of a computer spreadsheet. Tests were based on proposed
      standard method M27P of the National Committee for Clinical Laboratory Standards
      for antifungal agents. RPMI 1640 broth with extra glucose to a final
      concentration of 2% gave higher and more reproducible drug-free control readings
      without affecting susceptibility endpoint readings. An inoculum of 8 x 10(4)
      yeasts per ml prepared from a carbon-limiting broth culture without further
      standardization was found to give optimal control readings after 48 h of
      incubation at 37 degrees C. For flucytosine, fluconazole, itraconazole, and
      ketoconazole, endpoints based on 50% growth inhibition (50% inhibitory
      concentration) gave the minimum variation with inoculum size and the fewest
      endpoint differences with RPMI 1640 medium obtained from two different suppliers.
      The 50% inhibitory concentration was also the optimal endpoint for fluconazole
      and ketoconazole susceptibilities in comparison with broth macrodilution MICs
      determined by the method of the National Committee for Clinical Laboratory
      Standards. Intralaboratory reproducibility was determined by retrospective
      analysis of replicate results for isolates retested at random over a 2-year
      period. This approach showed less favorable reproducibility than has been
      reported from purpose-designed, prospective antifungal susceptibility studies,
      but it may better reflect real-life test reproducibility. Susceptibility data for
      616 clinical isolates of yeasts, representing 16 Candida and Saccharomyces spp.,
      confirmed the tendency of Candida lusitaniae isolates to show relatively low
      susceptibilities to amphotericin B, the tendency of Candida krusei isolates to
      show low flucytosine and fluconazole susceptibilities, and the presence of some
      isolates in the species Candida albicans, Candida glabrata, and Candida
      tropicalis with low susceptibilities to azole derivative antifungal agents. The
      study demonstrates the value of automation and standardization in all stages of
      yeast susceptibility testing, from plate preparation to data analysis.

PMID- 8540716
TI  - Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human
      brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de
      Castilla-la Mancha de Enfermedades Infecciosas.
AB  - Brucellosis is a common zoonosis in many parts of the world; the best regimen for
      the treatment of brucellosis has not been clearly determined. We have carried out
      a multicenter, open, controlled trial in five general hospitals in Spain to
      compare the efficacy and safety of doxycycline and rifampin (DR) versus
      doxycycline and streptomycin (DS) for the treatment of human brucellosis. The
      study included 194 ambulatory or hospitalized patients with acute brucellosis,
      without endocarditis or neurobrucellosis. The diagnostic criterion was isolation
      of Brucella species from blood or other tissues (n = 120) or a standard tube
      agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible
      clinical findings (n = 74). Patients were randomly assigned to receive either 100
      mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose
      for 45 days (DR group) or the same dose of doxycycline for 45 days plus
      streptomycin, 1 g/day, intramuscularly for 14 days (DS group). A lack of
      therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and
      in 2 of the 94 patients in the DS group (2%)(P = 0.10). Relapses occurred in 16
      of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the
      DS group (5.3%) (P = 0.02). When relapse was considered in combination with
      initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the
      DS group (7.45%) failed to respond to therapy (P = 0.0016). In general, therapy
      was well tolerated and only four patients (4%) in the DR group and two (2%) in
      the DS group had episodes of adverse effects necessitating discontinuation of
      treatment (P> 0.2). We conclude that a doxycycline-and-rifampin regimen is less
      effective than the doxycycline-and-streptomycin regimen in patients with acute
      brucellosis.

PMID- 8540717
TI  - Identification of daptomycin-binding proteins in the membrane of Enterococcus
      hirae.
AB  - Daptomycin, a lipopeptide antibiotic active against gram-positive bacteria, was
      preliminarily shown to inhibit lipoteichoic acid (LTA) synthesis as a consequence
      of membrane binding in the presence of Ca2+ (P. Canepari, M. Boaretti, M. M.
      Lleo, and G. Satta, Antimicrob. Agents Chemother. 34:1220-1226, 1990). In the
      present study, it is shown that, along with binding bacterial-membrane
      components, daptomycin binds the protein fraction with a noncovalent bond, as
      suggested by the instability of the bond in the presence of ionic detergents such
      as sodium dodecyl sulfate. Analysis of membrane proteins by isoelectric focusing
      electrophoresis reveals that five 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 to the
      main inhibition observed during LTA synthesis, two-dimensional thin-layer
      chromatography of lipids synthesized during daptomycin treatment was performed. A
      threefold increase in diglucosyl diacylglycerol is demonstrated, while the
      compounds phosphatidyl-alpha-kojibiosyldiacylglycerol, glycerophospho
      phosphatidyl-alpha-kojibiosyldiacylglycerol, and glycerophospho
      kojibiosyldiacylglycerol, which follow diglucosyl diacylglycerol in LTA
      synthesis, decrease progressively with time during the course of daptomycin
      treatment.

PMID- 8540718
TI  - Comparison of activities of rifapentine and rifampin against Mycobacterium
      tuberculosis residing in human macrophages.
AB  - The activities of rifapentine and rifampin against Mycobacterium tuberculosis
      residing in human monocyte-derived macrophages were determined. The MICs and MBCs
      of rifapentine for intracellular bacteria were two- to fourfold lower than those
      of rifampin. For extracellular bacteria, this difference was less noticeable.
      Nevertheless, the more favorable pharmacokinetics of rifapentine over rifampin
      was addressed in other experimental models. These models showed substantial
      differences after short pulsed exposures of the infected macrophages to the drugs
      and when the infected macrophages were exposed to changing drug concentrations
      that imitated the pharmacokinetic curves observed in blood. Once-a-week exposures
      to rifapentine concentrations equivalent to those attained in blood after one 600
      mg dose resulted during the first week in a dramatic decline in the number of
      bacteria, and this decline was maintained at a minimal level for a period of four
      weeks. The results of this study have shown the suitability of rifapentine for
      intermittent-treatment regimens. The prolonged effect of rifapentine found in
      this study may be associated with high ratios of intracellular accumulation,
      which were four- to fivefold higher than those found for rifampin. Further
      studies on the intracellular distribution of rifamycins and on the sites of
      actual interaction between the drugs and bacteria residing in macrophages are
      necessary.

PMID- 8540719
TI  - Effect of omeprazole on concentrations of clarithromycin in plasma and gastric
      tissue at steady state.
AB  - This study was conducted to determine (i) the effect of omeprazole on steady
      state concentrations of clarithromycin and 14-(R)-hydroxyclarithromycin in plasma
      and gastric mucosa, (ii) the effect of clarithromycin on steady-state
      concentrations of omeprazole in plasma, and (iii) the effect of clarithromycin on
      the suppression of gastric acid secretion by omeprazole. Twenty healthy,
      Helicobacter pylori-negative male subjects completed this three-period, double
      blind, randomized crossover study. In period 1, all subjects received 40 mg of
      omeprazole each morning for 6 days. Twenty-four-hour gastric pH monitoring took
      place on days -1 and 6. Pharmacokinetic sampling took place on day 6. In periods
      2 and 3, subjects were randomly assigned to receive either 40 mg of omeprazole or
      omeprazole placebo daily for 6 days plus clarithromycin (500 mg) every 8 h for 5
      days with a single 500-mg dose on day 6. Gastric tissue and mucus samples were
      obtained via endoscopy on day 5. Gastric pH monitoring and pharmacokinetic
      sampling took place on day 6. Two-week washout intervals separated the three
      study periods. Clarithromycin increased mean omeprazole area under the
      concentration-time curve from 0 to 24 h from 3.3 +/- 2.0 to 6.3 +/- 4.5
      micrograms.h/ml (P < 0.05) and harmonic mean half-life from 1.2 to 1.6 h (P <
      0.05) but did not significantly alter the effect of omeprazole on gastric pH.
      Mean clarithromycin area under the concentration-time curve from 0 to 8 h
      increased from 22.9 +/- 5.5 (placebo) to 26.4 +/- 5.7 micrograms.h/ml
      (omeprazole) (P < 0.05) when clarithromycin was administered with omeprazole.
      Analysis of variance revealed that mean concentrations of clarithromycin in
      tissue and mucus were statistically significantly higher when clarithromycin was
      given with omeprazole than when clarithromycin was given with placebo (P <0.001).
      Mean maximum observed concentrations of clarithromycin in the gastric fundus
      increased from 20.8 +/- 7.6 (placebo) to 24.3 +/- 6.4 micrograms/g (omeprazole),
      and those in the gastric mucous from 4.2 +/- 7.7 placebo to 39.3 +/- 32.8
      micrograms/g (omeprazole). Similar increases were observed for the 14-(R)
      hydroxyclarithromycin. These results show that omeprazole increases
      concentrations of clarithromycin in gastric tissue and mucus and may provide a
      mechanism for synergy between clarithromycin ad omeprazole that explains the
      excellent eradication of H. pylori seen in clinical trials.

PMID- 8540720
TI  - Reduced amoxicillin uptake into human gastric mucosa when gastric juice pH is
      high.
AB  - Amoxicillin when administered with gastric acid suppressors has been shown to be
      effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim
      of this investigator-blind crossover study was to determine if gastric mucosal
      amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male
      subjects (7 H. pylori positive and 8 H. pylori negative) were randomized to
      receive 150 mg of ranitidine twice a day, 300 mg of ranitidine twice a day, or no
      drug for 2 days prior to upper endoscopy. The last dose of ranitidine was given
      60 min prior to upper endoscopy, and amoxicillin (500 mg) was given 30 min prior
      to upper endoscopy. The amoxicillin concentrations in mucosal biopsy samples,
      gastric juice, and serum were determined by a standard microbiological bioassay
      technique. Mean amoxicillin levels were greater in samples of antrum, fundus, and
      duodenum for volunteers who received no ranitidine than in those receiving 300 mg
      of ranitidine (P < 0.05) and those receiving 150 mg of ranitidine (P < 0.05
      except for fundus). Amoxicillin levels in the antrum, fundus, and duodenum were
      negatively correlated with gastric juice pH (P < 0.005 for antrum; P < 0.001 for
      fundus and duodenum). There was no correlation between gastric juice pH and
      amoxicillin levels in either gastric juice or serum. The amoxicillin
      concentration in gastric juice was significantly higher with 300 mg of ranitidine
      than with no ranitidine (P < 0.05). Thus, lower gastric juice pH is associated
      with a higher rate of mucosal uptake of amoxicillin.

PMID- 8540721
TI  - In vitro antimycobacterial activities of pyrazinamide analogs.
AB  - We synthesized various pyrazine derivatives and pyrazinamide analogs and assayed
      their antimycobacterial activities in vitro in order to find new drugs which are
      more active against Mycobacterium tuberculosis than pyrazinamide and also active
      against Mycobacterium avium and Mycobacterium intracellulare. Of the drugs
      synthesized, four drugs, namely, pyrazine thiocarboxamide, N-hydroxymethyl
      pyrazine thiocarboxamide, pyrazinoic acid n-octyl ester, and pyrazinoic acid
      pivaloyloxymethyl ester, were not only bacteriostatic but also bacteriocidal
      against these three species of mycobacteria in vitro under conditions in which
      pyrazinamide showed no or little activity. In conclusion, these four drugs are
      possible candidates for new antimycobacterial agents, and animal experiments are
      now under way.

PMID- 8540722
TI  - Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory
      fluids of healthy volunteers.
AB  - The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in
      excretory fluids was investigated in 11 healthy volunteers. A single intravenous
      dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma,
      urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for
      enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography.
      Large differences in the concentration-time profiles of the excretory fluids
      analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure,
      as assessed by the area under the concentration-time curve. Excretory
      fluid/plasma area under the concentration-time curve ratios were found to be 1.67
      +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/- 0.07 for sweat,
      and 0.23 +/- 0.11 for tears. The elimination half-life of enoxacin from sweat
      (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46
      h). Oxoenoxacin was detected in urine and saliva and exhibited a higher renal
      clearance and a lower saliva exposure than the parent compound. In contrast to
      that of the metabolite, distribution of enoxacin in saliva was found to be time
      and pH dependent. In conclusion, our study revealed considerable differences in
      the distribution kinetics of enoxacin among various excretory sites. Because of
      distinct acidic and basic properties, the anionic oxometabolite significantly
      differs from the zwitterionic parent compound in its distribution
      characteristics.

PMID- 8540723
TI  - Effect of gentamicin dosing interval on therapy of viridans streptococcal
      experimental endocarditis with gentamicin plus penicillin.
AB  - This study compares the effects of a total daily dose of gentamicin given once a
      day (q.d.) or three times a day (t.i.d.) in the therapy of experimental
      endocarditis in rabbits caused by penicillin-susceptible, penicillin-tolerant, or
      penicillin-resistant viridans streptococci. Four isolates were used in vivo: one
      penicillin susceptible (MIC < or = 0.03 microgram/ml), one penicillin tolerant
      (MBC/MIC, < or = 0.03/ > 32 micrograms/ml), and two penicillin resistant (MICs =
      0.5 and 2 micrograms/ml). Animals were infected with one of the four isolates and
      assigned to one of the following treatment regimens: no treatment, procaine
      penicillin at 1.2 million IU intramuscularly (i.m.) t.i.d., procaine penicillin
      plus gentamicin at 1 mg/kg of body weight i.m. t.i.d., procaine penicillin plus
      gentamicin at 3 mg/kg i.m. q.d., or procaine penicillin plus gentamicin at 1
      mg/kg i.m. q.d. (only animals infected with the penicillin-susceptible isolate).
      Serum drug concentrations measured 30 min after administration of 1.2 million IU
      of penicillin and 1 or 3 mg of gentamicin per kg were 22.6, 3.8, and 8.5
      micrograms/ml, respectively. The reduced total daily dose of gentamicin was
      ineffective among animals infected with penicillin-susceptible viridans
      streptococci; treatment with 1 mg of gentamicin per kg per day plus penicillin
      was less effective (P < 0.05) than was treatment with 3 mg of gentamicin per kg
      per day plus penicillin. The 1-mg/kg/day gentamicin treatment regimen was not
      further studied. The gentamicin dosing interval did not significantly affect
      (q.d. versus t.i.d., P > 0.05) the relative efficacy of penicillin plus
      gentamicin for treatment of experimental endocarditis among animals infected with
      each of the four isolates tested.

PMID- 8540724
TI  - Formulation and efficacy of liposome-encapsulated antibiotics for therapy of
      intracellular Mycobacterium avium infection.
AB  - Mycobacterium avium is an intracellular pathogen that can invade and multiply
      within macrophages of the reticuloendothelial system. Current therapy is not
      highly effective. Particulate drug carriers that are targeted to the
      reticuloendothelial system may provide a means to deliver antibiotics more
      efficiently to M. avium-infected cells. We investigated the formulation of the
      antibiotics ciprofloxacin and azithromycin in liposomes and tested their
      antibacterial activities in vitro against M. avium residing within J774, a murine
      macrophage-like cell line. A conventional passive-entrapment method yielded an
      encapsulation efficiency of 9% for ciprofloxacin and because of aggregation
      mediated by the cationic drug, was useful only with liposomes containing < or =
      50 mol% negatively charged phospholipid. In contrast, ciprofloxacin was
      encapsulated with > 90% efficiency, regardless of the content of negatively
      charged lipids, by a remote-loading technique that utilized both pH and potential
      gradients to drive drug into preformed liposomes. Both the cellular accumulation
      and the antimycobacterial activity of ciprofloxacin increased in proportion to
      the liposome negative charge; the maximal enhancement of potency was 43-fold in
      liposomes of distearoylphosphatidylglycerol-cholesterol (DSPG-Chol) (10:5).
      Azithromycin liposomes were prepared as a freeze-dried preparation to avoid
      chemical instability during storage, and drug could be incorporated at 33 mol%
      (with respect to phospholipid). Azithromycin also showed enhanced
      antimycobacterial effect in liposomes, and the potency increased in parallel to
      the moles percent of negatively charged lipids; azithromycin in DSPG-Chol (10:5)
      liposomes inhibited intracellular M. avium growth 41-fold more effectively than
      did free azithromycin. Thus, ciprofloxacin or azithromycin encapsulated in stable
      liposomes having substantial negative surface charge is superior to
      nonencapsulated drug in inhibition of M.avium growth within cultured macrophages
      and may provide more effective therapy of M.avium infections.

PMID- 8540725
TI  - Characterization of antimicrobial resistance in enterococci of animal origin.
AB  - Among 97 enterococci cultured from animals, gentamicin MICs were > or = 2,000
      micrograms/ml for 9 isolates and between 250 and 1,024 micrograms/ml for 6
      isolates. For two isolates tested (gentamicin MICs, 256 and 512 micrograms/ml,
      respectively), there was no in vitro synergy with penicillin plus gentamicin,
      resistance was transferable, and there was no hybridization with a probe specific
      for 6'-aminoglycoside acetyltransferase-2"-aminoglycoside phosphotransferase. The
      results of the study indicate the presence of a unique gentamicin resistance
      genotype in enterococci of animal origin.

PMID- 8540726
TI  - In vitro activity of levofloxacin, singly and in combination with rifamycin
      analogs, against Mycobacterium leprae.
AB  - The in vitro susceptibility of Mycobacterium leprae to levofloxacin was studied
      by using two biochemical parameters to measure the metabolic activity of the
      organism. Levofloxacin consistently exhibited twofold greater bactericidal
      activity than ofloxacin, with the MIC being 0.75 microgram/ml. When combined with
      one of the three rifamycin analogs, synergism was obtained with KRM-1648 and
      rifabutin but not with rifampin.

PMID- 8540727
TI  - Biochemical basis for increased susceptibility to Cidofovir of herpes simplex
      viruses with altered or deficient thymidine kinase activity.
AB  - It has been observed that herpes simplex virus mutants with deficient or altered
      thymidine kinase activity are more susceptible to Cidofovir (CDV; 1-[(S)-3
      hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate) in tissue culture than are
      the parental strains. During infection of cells, the elevation of the dCTP pool
      by thymidine kinase mutant viruses is less than that induced by the wild-type
      virus. The competition between CDV diphosphate and dCTP at the viral polymerase
      is therefore changed in favor of CDV diphosphate, enhancing its activity.

PMID- 8540728
TI  - In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD
      138312 versus enterococci.
AB  - Certain new fluoroquinolones have high activity against enterococci. Against
      Enterococcus faecalis (n = 18), MICs at which 90% of the isolates were inhibited
      were as follows (in micrograms per milliliter): clinafloxacin, 0.125; CI-990,
      0.5; and PD 138312, 0.25 (compared with 1 microgram/ml for ciprofloxacin and 2
      micrograms/ml for ofloxacin). Strains producing beta-lactamase or that were
      vancomycin resistant or resistant to high-level gentamicin were not quinolone
      cross-resistant. The drugs were bactericidal and were unaffected by 50% human
      serum. Oral efficacies (in milligrams per kilogram of body weight for 50%
      protective doses) in lethal mouse infections with quinolone-susceptible strains
      were 4.3 to 24 for clinafloxacin, 7.2 to 39 for CI-990, 7.2 to 76 for PD 138312,
      and 41 to > 100 for ciprofloxacin; when the drugs were given subcutaneously, the
      order was similar and values ranged from 1.1 to 12.5. Clinafloxacin, CI-990, and
      PD 138312 may have therapeutic potential in systemic enterococcal infections in
      humans.

PMID- 8540729
TI  - Resistance of Candida albicans biofilms to antifungal agents in vitro.
AB  - Biofilms formed by Candida albicans on small discs of catheter material were
      resistant to the action of five clinically important antifungal agents as
      determined by [3H]leucine incorporation and tetrazolium reduction assays.
      Fluconazole showed the greatest activity, and amphotericin B showed the least
      activity against biofilm cells. These findings were confirmed by scanning
      electron microscopy of the biofilms.

PMID- 8540730
TI  - A beta-lactamase from Serratia marcescens hydrolyzing the 2-carboxypenam T-5575.
AB  - A beta-lactamase was purified from Serratia marcescens GN16694; it hydrolyzed T
      5575 and oxime-type cephalosporins, i.e., cefuroxime and ceftazidime. Its
      isoelectric point and molecular weight were 8.6 and 42,000, respectively. This
      enzyme was not inhibited by EDTA and clavulanic acid. This enzyme is an unusual
      beta-lactamase and has been classified as a group 1 cephalosporinase.

PMID- 8540731
TI  - Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin.
AB  - The effects of single coadministrations of one of three traditional Chinese
      medicines, Hotyu-ekki-to, Rikkunshi-to, and Juzen-taiho-to, on the
      pharmacokinetics of levofloxacin (LVFX) were investigated with eight healthy
      volunteers in an open, random crossover fashion. Subjects each received a single
      oral dose of LVFX (200 mg) alone and then with a single coadministration of each
      Chinese medicine. There were no significant differences in any pharmacokinetic
      parameters of LVFX between the groups. Also, no significant changes in the
      urinary recovery (> 80%) and renal clearance of LVFX were observed. These results
      indicate that the Chinese medicines tested have no significant effect on the rate
      and extent of bioavailability or renal excretion of LVFX.

PMID- 8540732
TI  - Influence of a newly developed quinolone, T-3761, on pharmacokinetics of
      theophylline in rats.
AB  - The effect of a new quinolone, T-3761, on the pharmacokinetics and metabolism of
      theophylline was investigated with rats. T-3761 at a high dose (20 mg/kg of body
      weight) was injected intravenously 10 min before an intravenous administration of
      theophylline (10 mg/kg). The presence of T-3761 slightly delayed the
      disappearance of theophylline from plasma. Parameters related to the
      pharmacokinetic interaction between theophylline and T-3761 were estimated by
      noncompartmental methods. A significant decrease (approximately 25%) in the
      systemic clearance of theophylline was observed in the presence of T-3761.
      However, no significant changes between the control group and the T-3761-treated
      groups in the volume of distribution at a steady state were observed.
      Pretreatment with T-3761 increased the urinary excretion of unchanged
      theophylline (by approximately 25%) and decreased the nonrenal clearances (by
      approximately 30%), indicating that T-3761 inhibits the metabolism of
      theophylline. These findings suggest that T-3761 at the dose used in this study
      affects the pharmacokinetics and metabolism of theophylline.

PMID- 8540733
TI  - Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis
      and Staphylococcus aureus.
AB  - Macrolide antibiotics are clinically important antibiotics which are effective
      inhibitors of protein biosynthesis in bacterial cells. We have recently shown
      that some of these compounds also inhibit 50S ribosomal subunit formation in
      Escherichia coli. Now we show that certain macrolides have the same effect in two
      gram-positive organisms, Bacillus subtilis and Staphylococcus aureus. Assembly in
      B. subtilis was prevented by erythromycin, clarithromycin, and azithromycin but
      not by oleandomycin. 50S subunit formation in S. aureus was prevented by each of
      seven structurally related 14-membered macrolides but not by lincomycin or two
      streptogramin antibiotics. Erythromycin treatment did not stimulate the breakdown
      of performed 50S subunits in either organism. The formation of the 30S ribosomal
      subunit was also unaffected by these compounds. Assembly was also inhibited in a
      B. subtilis strain carrying a plasmid with the ermC gene that confers macrolide
      resistance by rRNA methylation. These results suggest that ribosomes contain an
      additional site for the inhibitory functions of macrolide antibiotics.

PMID- 8540734
TI  - Sequences of conserved region in the A subunit of DNA gyrase from nine species of
      the genus Mycobacterium: phylogenetic analysis and implication for intrinsic
      susceptibility to quinolones.
AB  - The sequences of a conserved region in the A subunit of DNA gyrase corresponding
      to the quinolone resistance-determining region were determined for nine
      mycobacterial species and were compared. Although the nucleotide sequences were
      highly conserved, they clearly differentiated one species from another. The
      results of the phylogenetic analysis based on the sequences of the quinolone
      resistance-determining regions were compared with those provided by the 16S rRNA
      sequences. Deduced amino acid sequences were identical within the nine species
      except for amino acid 83, which was frequently involved in acquired resistance to
      quinolones in many genera, including mycobacteria. The presence at position 83 of
      an alanine for seven mycobacterial species (M. tuberculosis, M. bovis BCG, M.
      leprae, M. avium, M. kansasii, M. chelonae, and M. smegmatis) and of a serine for
      the two remaining mycobacterial species (M. fortuitum and M. aurum) correlated
      well with the MICs of ofloxacin for both groups of species, suggesting the role
      of this residue in intrinsic susceptibility to quinolones in mycobacteria.

PMID- 8540735
TI  - Effect of cefotaxime or ceftriaxone treatment on nasopharyngeal Haemophilus
      influenzae type b colonization in children.
AB  - The effects of cefotaxime and ceftriaxone treatment on nasopharyngeal carriage of
      Haemophilus influenzae type b (Hib) were prospectively studied with 53 children
      with invasive Hib disease. Nasopharyngeal aspirates were monitored during
      therapy. Hib was eliminated within 2 days in 92% of patients and was eliminated
      in all patients after the third day of antibiotic treatment.

PMID- 8540736
TI  - In vitro antimicrobial susceptibilities of strains of Yersinia pestis.
AB  - The in vitro activities of 14 antimicrobial agents were determined for 78 strains
      of Yersinia pestis. The most active antibiotics were ceftriaxone and
      ciprofloxacin, followed by ofloxacin and ampicillin. The agents traditionally
      used for the treatment of plague (streptomycin, tetracycline, and
      chloramphenicol) were considerably less active. Azithromycin showed poor activity
      against all strains.

PMID- 8540737
TI  - Evaluation of high-dose regimen of paromomycin against cryptosporidiosis in the
      dexamethasone-treated rat model.
AB  - In the dexamethasone-treated rat model of cryptosporidiosis, paromomycin was
      effective at a dosage of 50 mg/kg/day or more for ileal infection and 200
      mg/kg/day or more for cecal infection. At 1 and 3 weeks after treatment, a
      persistent infection was demonstrated in all rats. These results confirm the
      anticryptosporidial activity of paromomycin and underscore the limitations of
      this compound because of its potential toxicity at such high dosages and its
      inability to eradicate the infection.

PMID- 8540738
TI  - Influence of dexamethasone on efficacy of ceftriaxone and vancomycin therapy in
      experimental pneumococcal meningitis.
AB  - Using a rabbit model of meningitis, we sought to determine whether concomitant
      use of dexamethasone affects the penetration and efficacy of ceftriaxone or
      vancomycin in cerebrospinal fluid. Rabbits were inoculated with a penicillin
      sensitive strain of Streptococcus pneumoniae and treated with ceftriaxone or
      vancomycin with or without dexamethasone. In the ceftriaxone-treated groups, no
      statistically significant differences were seen between the group treated with
      dexamethasone and that without dexamethasone; however, in the vancomycin-treated
      groups we found statistically significant lower cerebrospinal fluid vancomycin
      levels at 2 h in the dexamethasone-treated rabbits and differences in bacterial
      killing.

PMID- 8540739
TI  - Absorption of ciprofloxacin in patients with diabetic gastroparesis.
AB  - The purpose of this study was to assess the pharmacokinetic profile of
      ciprofloxacin in 12 patients with diabetic gastroparesis. Patients received both
      a single 500-mg oral (p.o.) dose and a single 400-mg intravenous (i.v.) dose of
      ciprofloxacin separated by a 1-week washout period. Pharmacokinetic parameters
      (means +/- standard deviations) for the p.o. and i.v. doses were as follows:
      areas under the concentration-time curve from 0 h to infinity, 9.74 +/- 2.59 and
      11.78 +/- 3.18 micrograms.h/ml, respectively; maximum concentrations of drug in
      serum, 2.13 +/- 0.67 and 4.21 +/- 1.07 micrograms/ml, respectively; and half
      lives, 4.03 +/- 0.58 and 4.20 +/- 0.58 h, respectively. The ratio of the areas
      under the concentration-time curves from 0 h to infinity for the p.o. and i.v.
      doses was 0.84, with a 90% confidence interval of 0.68 to 0.98; the mean absolute
      bioavailability was calculated to be 67% (range, 43 to 82%). From these data it
      appears that ciprofloxacin is adequately absorbed in patients with diabetic
      gastroparesis.

PMID- 8540740
TI  - Sequence and analysis of the rpoB gene of Mycobacterium smegmatis.
AB  - The rpoB gene encodes the beta subunit of the DNA-dependent RNA polymerase of
      bacteria. Mutations in defined areas result in resistance to rifampin.
      Mycobacterium smegmatis is naturally resistant to rifampin, but analysis of the
      rpoB gene revealed no identifiable rifampin resistance mutations. Another
      mechanism of resistance may be present.

PMID- 8540741
TI  - Culture microtitration: a sensitive method for quantifying Leishmania infantum in
      tissues of infected mice.
AB  - We developed a microtitration method to determine the parasite burdens in
      homogenized organs of mice infected with Leishmania infantum. This method proved
      more sensitive than direct enumeration of amastigotes in stained organs, was
      appropriate for describing the kinetics of infection, and can be considered for
      physiopathological or pharmaceutical experimental studies.

PMID- 8540742
TI  - Effect of broth enrichment cultures on ability to detect carriage of
      Staphylococcus aureus.

PMID- 8540743
TI  - Antiretroviral activity of stavudine (2',3'-didehydro-3'-deoxythymidine, D4T).
AB  - Stavudine, 2',3'-didehydro-3'-deoxythymidine (D4T), is a potent inhibitor of HIV
      1 reverse transcriptase in vitro. In clinical studies, stavudine has excellent
      oral bioavailability in excess of 80%. The dose-limiting toxicity is peripheral
      neuropathy, which occurred in 15% of stavudine versus 6% of zidovudine-treated
      patients for 80 weeks in a randomized, blinded, phase III trial. Stavudine
      treated groups have experienced significant increases in mean CD4 cell counts and
      decreases in both mean serum p24 antigen levels and infectious HIV titers in
      peripheral blood mononuclear cells. In subjects with prior zidovudine treatment,
      the duration of these responses is limited; CD4 counts and serum p24 antigen
      levels return to baseline after approximately 6 months. The effect of stavudine
      on clinical outcome and survival has not yet been established in comparative
      trials. Stavudine offers an additional therapeutic option to those individuals
      who are refractory to or intolerant of other available antiretrovirals.

PMID- 8540744
TI  - Antiviral properties of simple difunctionalized enols targeted to the HIV-1
      protease.
AB  - The human immunodeficiency virus type 1 (HIV-1) protease catalyses the specific
      cleavage of the virion structural polyproteins p55gag and p160gag-pol and is,
      therefore, essential for viral maturation. We have previously reported a series
      of low molecular weight non-peptidic enol-based compounds that inhibit the HIV-1
      protease activity in a competitive fashion (Vaillancourt et al., Bioorg. Med.
      Chem., 2 (1994) 343-355). Here we demonstrate that VS-215 and VS-261, two of
      these non-peptidic inhibitors, impair viral polyprotein maturation and exhibit
      antiviral activity in infected MT4 cells. The ID50 for these two compounds ranged
      between 24 and 50 microM whereas their TD50 ranged between 60 and 200 microM
      depending on the cell lines used. The calculated therapeutic index of these two
      inhibitors both had values of 2.5 even though they were shown to be non cytotoxic
      at their ID50. Their calculated permeability index ranged between 0.09 and 0.79
      suggesting that these enol-based inhibitors efficiently reach the site of
      protease activity. These results provide new information on the therapeutic
      potential of this new class of protease inhibitors and emphasize the usefulness
      of enol chemistry in the development of anti-HIV-1 protease inhibitors.

PMID- 8540745
TI  - Activity of various thiocarboxanilide derivatives against wild-type and several
      mutant human immunodeficiency virus type 1 strains.
AB  - A large variety of carboxanilide derivates in which the original oxathiin moiety
      present in the prototype compound UC84 was replaced by a non-cyclic lipophilic
      entity has been evaluated for their inhibitory effect against wild-type human
      immunodeficiency virus type 1 (HIV-1/IIIB) and several mutant viruses derived
      thereof (i.e. HIV-1/138-Lys, HIV-1/181-Cys, HIV-1/106-Ala and HIV-1/100-IIe).
      Isopropoxy was the most favorable substituent resulting in molecules that were
      markedly inhibitory to the wild-type (EC50 0.004-0.04 microgram/ml) as well as
      the mutant HIV-1 strains (EC50 0.06-0.75 microgram/ml). In this respect, they
      proved superior to several other HIV-1-specific non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) that are currently the subject of clinical
      trials. One of the most potent HIV-1 inhibitors among the thiocarboxanilide
      derivatives, namely UC38, selected for a mutant virus strain in which Lys at
      position 101 and Gly at position 190 of the reverse transcriptase was replaced by
      Glu.

PMID- 8540746
TI  - Evidence for antiviral activity of glutathione: in vitro inhibition of herpes
      simplex virus type 1 replication.
AB  - The role of glutathione (GSH) in the in vitro infection and replication of human
      herpes simplex virus type 1 (HSV-1) was investigated. Intracellular endogenous
      GSH levels dramatically decreased in the first 24 h after virus adsorption,
      starting immediately after virus challenge. The addition of exogenous GSH was not
      only able to restore its intracellular levels almost up to those found in
      uninfected cells, but also to inhibit > 99% the replication of HSV-1. This
      inhibition was concentration-dependent, not related to toxic effects on host
      cells and also maintained if the exogenous GSH was added as late as 24 h after
      virus challenge, i.e. when virus infection was fully established. Electron
      microscopic examination of HSV-1-infected cells showed that GSH dramatically
      reduced the number of extracellular and intracytoplasmic virus particles, whereas
      some complete nucleocapsids were still detected within the nuclei of GSH-treated
      cells. Consistent with this observation, immunoblot analysis showed that the
      expression of HSV-1-glycoprotein B, crucial for the release and the infectivity
      of virus particles, was significantly decreased. Data suggest that exogenous GSH
      inhibits the replication of HSV-1 by interfering with very late stages of the
      virus life cycle, without affecting cellular metabolism.

PMID- 8540747
TI  - Propranolol suppresses reactivation of herpesvirus.
AB  - Herpes simplex virus type 1 (HSV-1) reactivates from the nervous system and
      causes recurrent disease in end organs such as the eye and the lips. We found
      that the beta-adrenergic receptor blocker, propranolol, reduces HSV-1
      reactivation in an animal model. Mice latent for McKrae strain HSV-1 were
      injected with propranolol or saline once a day for 3 successive days, and
      subjected to a brief period of hyperthermia on the second day to induce
      reactivation. Twenty-four hours after the third injection, swabs of the ocular
      surface and homogenates of the corneas and trigeminal ganglia were analyzed for
      the presence of infectious virus and viral DNA. Treatment with propranolol
      significantly decreased the appearance of infectious virus in the tear film,
      cornea, and trigeminal ganglia (P < 0.05, chi 2-test). The results suggest a
      possible new pharmacologic approach to suppressing herpesvirus reactivation in
      the nervous system and thereby preventing recurrent disease.

PMID- 8540748
TI  - Topical treatment of recurrent mucocutaneous herpes with ascorbic acid-containing
      solution.
AB  - We carried out a randomized double-bind, placebo-controlled clinical trial on the
      topical treatment of recurrent mucocutaneous herpes with a strong water solution
      of Ascoxal, an ascorbic acid-containing pharmaceutical formulation with mucolytic
      and non-specific antimicrobial activities. The lesion was firmly pressed with a
      cotton wool pad soaked in drug solution 3 times for 2 min with 30-min intervals
      on the first day only. Evaluation of the effects was by daily recordings of
      several different symptoms, including the presence and severity of erythema,
      induration, papulae or vesicles and scab by both the patient and a trained nurse,
      and by virus culture. Fourteen episodes with active treatment and 18 with the
      placebo were analyzed. According to the patients' records, the active treatment
      resulted in a significantly smaller cumulative number of days with scab (P <
      0.01), or with any remaining symptom (P < 0.02) and significantly fewer occasions
      of worsening of any symptom after the treatment (P < 0.05). According to the
      nurse's records, the persistence of scabs was significantly shorter in the active
      treatment group (means 3.4 vs 5.9 days, P = 0.03). Virus culture after the first
      day of treatment yielded herpes simplex virus significantly less frequently in
      the active treatment group than in the placebo group (P < 0.01). In conclusion, a
      brief treatment with this ascorbic acid-containing preparation resulted in
      statistically significant clinical and antiviral effects, which calls for further
      and more extensive studies with a more intensive treatment schedule.

PMID- 8540749
TI  - Inhibitory action of acyclovir (ACV) and penciclovir (PCV) on plaque formation
      and partial cross-resistance of ACV-resistant varicella-zoster virus to PCV.
AB  - Penciclovir has potent antiviral activity against varicella-zoster virus (VZV).
      We have characterized the inhibitory effects of penciclovir and acyclovir on the
      plaque formation of cell-free VZV and cross-resistance of acyclovir-resistant VZV
      to penciclovir. The apparent effective concentration for 50% plaque reduction
      (EC50) of penciclovir determined on the third day was significantly lower than
      that determined on the fourth or fifth day. The size of plaques was smaller in
      the presence of penciclovir than in the presence of acyclovir. The effective
      concentrations for 50% reduction of the number of infected cells per plaque were
      1.40 and 5.00 micrograms/ml for penciclovir and acyclovir, respectively. Thus
      penciclovir suppressed spread of infection within developing plaques more
      efficiently than acyclovir. Five acyclovir-resistant VZV strains with altered DNA
      polymerase selected by acyclovir were examined for cross-resistance to
      penciclovir. They were 11- to 18-fold more resistant to ACV than the parent
      strain, but only 4- to 5-fold more resistant to PCV. Penciclovir-triphosphate
      carrying the 3'-hydroxyl group of 2'-deoxyribose might have better affinity to
      the altered viral DNA polymerase than acyclovir-triphosphate without the 3'
      hydroxyl group.

PMID- 8540750
TI  - Synthesis and anti-HIV-1 activity of novel TSAO-T derivatives modified at the 2'-
      and 5'-positions of the sugar moiety.
AB  - Novel analogues of the anti-HIV-1 agent TSAO-T, [1-[2',5'-bis-O-(tert-
      butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5"-(4"-amino- 1",2"
      oxathiole-2",2"-dioxide) and its 3-methyl counterpart TSAO-m3T were obtained by
      modifications at positions 2' or 5' of the sugar moiety. These compounds were
      evaluated for their inhibitory effect on HIV-1 and HIV-2 replication in cell
      culture. Introduction of new groups at the 5'-position (i.e. esters, benzylether
      and silylethers) resulted in compounds that were either inactive or less active
      than the parent compounds (TSAO-T and TSAO-m3T). Attempts to introduce small
      silyl ether groups at this position were not successful since these products
      decomposed during purification. Similar modifications at the 2'-position had a
      much less pronounced influence on the anti-HIV-1 activity.

PMID- 8540751
TI  - Synthesis, antiviral activity and enzymatic phosphorylation of 9
      phosphonopentenyl derivatives of guanine.
AB  - (E)-9-(5-Phosphonopent-4-enyl)guanine and (E)-9-[3-(hydroxymethyl)-5-
      phosphonopent-4-enyl]guanine which bear a vinyl phosphonate moiety as a mimic of
      the phosphate group were synthesized. Their activities against human
      immunodeficiency virus type-1 (HIV-1), herpes simplex virus type-1 (HSV-1) and
      human cytomegalovirus (HCMV) were evaluated in vitro in parallel with those of 9
      (5-phosphonopentyl)guanine and 9-(5,5-difluoro-5- phosphonopentyl)guanine. Both
      vinyl phosphonates exhibited anti-HIV-1 and anti-HCMV activities, whereas the
      methyl- and difluoromethyl phosphonate analogues were inactive. The selectivity
      index, calculated as the ratio of the toxicity for the host cells (50% reduction
      in cell viability or in [methyl-3H]thymidine incorporation) to the 50% inhibitory
      concentration for HIV-1 replication, was the highest for (E)-9-[3-(hydroxymethyl)
      5-phosphonopent-4-enyl]guanine. The acyclonucleotide analogues were also studied
      as substrates of guanylate kinase, an enzyme believed to play a critical role in
      the conversion of acyclic phosphate and phosphonate derivatives of guanine to
      their antivirally active diphosphate derivatives. (E)-9-(5-Phosphonopent-4-
      enyl)guanine and (E)-9-[3-(hydroxymethyl)-5-phosphonopent-4-enyl]guanine were
      good substrates of guanylate kinase, being phosphorylated with efficiencies of 14
      and 36% of that determined for GMP, respectively. These results contrast with the
      poor efficiency found for 9-(5-phosphonopentyl)guanine (0.3%) and the lack of
      phosphorylation of 9-(5,5-difluoro-5-phosphonopentyl)guanine by guanylate kinase
      (Nave et al. (1992) Arch. Biochem. Biophys. 295, 253-257). The role of the vinyl
      phosphonate group in the expression of the anti-HIV-1 activity of the
      phosphonopentenyl derivatives of guanine is discussed.

PMID- 8540752
TI  - In vitro and in vivo enhancement of ddI activity against Rauscher murine leukemia
      virus by ribavirin.
AB  - Ribavirin has been reported to enhance the activity of ddI against HIV. We
      explored this enhancement of antiviral activity in Rauscher murine leukemia virus
      (RMuLV) models in vitro and in vivo. The significant finding in these studies was
      that combinations of the drugs exhibited virus titer reductions that were greater
      than would be expected if the drug interactions were simply additive. These
      effects were designated synergistic by the method of Prichard and Shipman
      (Prichard, M.N. and Shipman, C., Jr. (1990). A three-dimensional model to analyze
      drug-drug interaction, Antiviral Res. 14, 181-206). In addition to the antiviral
      synergy, we also observed some synergistic toxicity in the animal model.

PMID- 8540753
TI  - The ribonucleotide reductase inhibitor (E)-2'-fluoromethylene-2'-deoxycytidine
      (MDL 101,731): a potential topical therapy for herpes simplex virus infection.
AB  - The ribonucleotide reductase inhibitor MDL 101,731 was examined for antiviral
      activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro
      and in combination with acyclovir in the murine zosteriform model of HSV-1
      infection. The in vitro antiviral activity (IC50) for both serotypes of HSV was
      similar and in the range 23-98 nM for Vero cells. Comparable activities were
      obtained against acyclovir-resistant viruses. In the zosteriform model, topical
      combination therapy of MDL 101,731 with acyclovir (5%:5% w/w) applied 48 h after
      infection was more effective than acyclovir alone and even appeared to promote
      lesion resolution.

PMID- 8540754
TI  - Novel sulfonated and phosphonated analogs of distamycin which inhibit the
      replication of HIV.
AB  - A series of novel distamycin-related polyanionic compounds were compared for
      their anti-HIV activity. Several were highly potent inhibitors of HIV virus
      induced cell killing and viral replication of a wide variety of laboratory
      isolates, as well as a monocytotropic virus and a clinical isolate in human
      peripheral blood lymphocytes. These compounds are structurally different from
      other sulfonic acid containing compounds reported to be potent inhibitors of the
      human immunodeficiency virus (HIV) in two respects: (1) they are structurally
      related to the non-toxic minor groove DNA binder distamycin; and (2) a number of
      them contain the aromatic phosphonic acid group. The compounds that were
      evaluated can be categorized into monomeric or dimeric ureido structural classes
      incorporating the bisamido-N-methylpyrrolenaphthalene-sulfonic acid group, with
      differences in the number and position of the sulfonic acids on the naphthalene
      rings. Broader structure-activity studies were made possible through the
      synthesis and evaluation of the compounds containing only a single N
      methylpyrrole unit, those incorporating the N-methylpyrazole structure, and
      compounds having the isosteric phosphonic acid group substituted for the sulfonic
      acid group. One of the most potent of the inhibitors was
      2,2'[4,4'[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide- 1,1'-dimethyl]]
      4,6,8 naphthalenetrisulfonic acid] hexasodium salt, NSC 651015. This compound,
      the phosphonic acid analog NSC 662162, and the monomeric compound NSC 651018 were
      studied to determine the mechanism of their inhibitory activity. Mechanistic
      studies revealed that inhibition was due to the disruption of virus attachment to
      CD(4+)-susceptible cells and a further restraint on fusion of virus and cell
      membranes. The relative tolerance of these compounds in mice suggests that
      sufficient antiviral concentrations could be reached in vivo and thus may prove
      valuable in the treatment of AIDS patients.

PMID- 8540755
TI  - Inhibition of the enteroviruses that cause acute hemorrhagic conjunctivitis (AHC)
      by benzimidazoles; enviroxime (LY 122772) and enviradone (LY 127123).
AB  - Enviradone (EvirD, (E)-1-[(1-methylethyl) sulfonyl]-6-(1-phenyl-1-propenyl)-1 H-
      benzimidazole-2-amine) and Enviroxime (EvirX, 2-amino-1-(isopropyl-sulfonyl)-6
      benzimidazole phenyl ketone oxime) inhibited enterovirus 70 (EV70) and
      coxsackievirus A24 variant (CA24v) infection of conjunctival and laryngeal cells.
      On average, the continuous presence of 1-3 micrograms of EvirD or EvirX/ml in
      cell cultures acutely infected with EV70 or CA24v inhibited virus production (> 2
      log10 reduction) and 100% of the viral cytopathogenic effect (CPE). The 50% CPE
      inhibitory dose (ID50) for EvirD and EvirX against 11 EV70 and 15 CA24v isolates
      ranged from 0.01 to 0.3 microgram and 0.01-0.65 microgram/ml, respectively. The
      mean ID50 for EvirD and EvirX against the 26 AHC viruses was 0.17 +/- 0.12
      microgram and 0.13 +/- 0.14 microgram/ml, respectively. Pretreatment for 15 min
      with 3 micrograms EvirX/ml or for 1-2 h with 3 micrograms EvirD/ml protected
      conjunctival cells against viral CPE. The cells were resistant to infection for 1
      2 h at 33 and 37 degrees C after removal of EvirD and EvirX. The addition of 10
      micrograms EvirD/ml up to 6 h or 10 micrograms EvirX/ml 1-2 h after low
      multiplicity infection inhibited viral CPE. Ten-fold less EvirD inhibited EV70
      when added to glioma cells 2 h before infection than when added 2 h after
      infection. Our results indicate that EvirX and EvirD inhibit AHC viruses in vitro
      at concentrations that are not cytotoxic and suggest that EvirX or EvirD may be
      prove useful against AHC.

PMID- 8540756
TI  - Differential inhibition of reverse transcriptase and cellular DNA polymerase
      alpha activities by lignans isolated from Chinese herbs, Phyllanthus myrtifolius
      Moon, and tannins from Lonicera japonica Thunb and Castanopsis hystrix.
AB  - Two lignans, phyllamycin B and retrojusticidin B isolated from Phyllanthus
      myrtifolius Moon have been demonstrated to have a strong inhibitory effect on
      human immunodeficiency virus-1 reverse transcriptase activity (HIV-1 RT), but
      much less inhibitory effect on human DNA polymerase-alpha (HDNAP-alpha) activity.
      Fifty percent inhibitory concentrations of phyllamycin B and retrojusticidin B
      were determined to be 3.5 and 5.5 microM for HIV-1 RT, and 289 and 989 microM for
      HDNAP-alpha, respectively. The mode of inhibition was found to be non-competitive
      inhibition with respect to template-primer and triphosphate substrate. Several
      tannins such as caffeoylquinates (CQs) isolated from Lonicera japonica Thunb,
      galloylquinates (GQs) and galloylshikimates (GSs) purified from Castanopsis
      hystrix were shown to have a much less selective inhibitory effect on HIV-1 RT.

PMID- 8540757
TI  - Vertebrate brains contain a broadly active antiviral substance.
AB  - Brain tissue extracts from vertebrates were examined for non-specific, broad
      spectrum virus inhibitors, previously identified and characterized from other
      body tissues and fluids. An antiviral activity found in human, bovine, ovine,
      porcine, lapine, murine and piscine brain tissues shares some properties with a
      contact blocking-virus inhibitor, which was previously found only in cell culture
      supernatants. The inhibitor was active against (in order of sensitivity to
      inhibitor) Banzi, Sindbis, Bunyamwera, Newcastle disease, herpes simplex I,
      Semliki forest, polio I, mengo, vaccinia and vesicular stomatitis viruses. It is
      approximately 4000 kDa and possesses a complex structure containing protein,
      carbohydrate and lipid moieties. The inhibitor does not directly neutralize virus
      or induce an antiviral state in cells, but appears to act early in the
      replication cycle, most likely by preventing virus attachment to target cells.
      Its occurrence in concentrations sufficient to reduce virus yield in cell
      cultures at least 30-fold may indicate a role in limiting viral infections of the
      central nervous system.

PMID- 8540758
TI  - Characterization of the non-specific humoral and cellular antiviral immunity
      stimulated by the chloroform-methanol residue (CMR) fraction of Coxiella
      burnetii.
AB  - Modulation of the immune response by the chloroform-methanol residue (CMR) of
      phase I Coxiella burnetii whole cell was studied in Rift Valley fever virus
      infected, or in naive endotoxin-non-responder C3H/HeJ mice. A single dose of CMR
      completely protected the mice from viral infection. Treating virus-infected mice
      with antibodies directed against interferons alpha/beta (IFN-alpha beta) and
      gamma (IFN-gamma) eliminated the CMR-induced protection. CMR stimulated the
      production of high levels of IFN-alpha/beta and 2'-5'-oligoadenylate synthetase
      activities in sera of the CMR-treated mice. IFN-gamma was present in supernatants
      of cultured spleen cells of CMR-treated, virus-infected mice, but not in their
      serum. Priming mice with CMR optimized the release of INF-gamma, interleukin-1
      alpha (IL-1 alpha) and IL-6 from splenocytes in vitro. When stimulated in vitro,
      IL-2 and granulocyte-macrophage stimulating factor (GM-CSF) did not require in
      vivo priming for release from cultured spleen cells. Fluorescence-assisted
      cytometry of CMR-treated mouse spleen cells showed there was a CMR-dependent
      increase in the percentage of T-cells and Ia-positive T-cells. There also was a
      biphasic increase in the ratio between Th (L3T4) and Ts (Lyt2) cells. Biological
      activities stimulated by CMR indicate that CMR is a potent immunostimulant, which
      may modulate specific and non-specific antiviral responses.

PMID- 8540759
TI  - In vitro inhibition of human cytomegalovirus replication in human foreskin
      fibroblasts and endothelial cells by ascorbic acid 2-phosphate.
AB  - Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting
      derivative of L-ascorbic acid, against several human cytomegalovirus (CMV)
      strains was examined in cultures of human foreskin fibroblasts (HFF) and
      endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no
      effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA)
      while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of
      both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF
      cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV
      infection. Antiviral effects were significantly increased in cultures pretreated
      with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM
      ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in
      EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF,
      respectively) was observed. Pretreatment for three subcultures with ASC-2P
      inhibited virus yield 50- to 100-fold in EC and 100- to 1000-fold in HFF. The
      continuous presence of ASC-2P was not required for its antiviral activity. A
      significantly higher reduction of virus replication with ganciclovir and
      foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The
      results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral
      activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of
      CMV infection.

PMID- 8540761
TI  - Inhibitory effect of bafilomycin A1, a specific inhibitor of vacuolar-type proton
      pump, on the growth of influenza A and B viruses in MDCK cells.
AB  - We studied the effect of bafilomycin A1 (Baf-A1), a novel and highly specific
      inhibitor for vacuolar-type proton (V-H+) pump, on the growth of influenza A and
      B viruses in Madin-Darby canine kidney cells. Vital fluorescence microscopic
      study showed that Baf-A1 induced the complete disappearance of acidified
      compartments such as endosomes and lysosomes both in infected and uninfected
      cells by the treatment with 0.1 microM inhibitor for 1 h at 37 degrees C. In
      addition, virus growth was inhibited when Baf-A1 was present from 1 h before
      infection to the end of incubation, or added within as early as 5-10 min after
      infection. Conversely, the virus growth was recovered in correlation with the
      reappearance of acidified compartments after removal of Baf-A1. These data
      suggest that Baf-A1-sensitive V-H+ pumps are solely responsible for the
      acidification of endosomes and lysosomes, and thus Baf-A1 inhibits the growth of
      influenza A and B viruses by affecting the acidified compartments in which low pH
      is essential for the uncoating process of influenza virus growth at an early
      stage of infection.

PMID- 8540760
TI  - Pharmacokinetics of zidovudine and didanosine during combination therapy.
AB  - While the combination of zidovudine and didanosine is used in HIV-infected
      patients with more advanced disease, the possibility of a pharmacokinetic
      interaction between these two drugs remains controversial. Zidovudine doses of
      50, 100, and 200 mg, combined with 67, 167, and 250 mg of didanosine were
      evaluated in 11 asymptomatic HIV-infected patients after receiving 24 weeks of
      combination therapy in AIDS Clinical Trials Group protocol 143. The
      pharmacokinetic parameters of zidovudine and didanosine were similar to those
      obtained with each drug given as monotherapy in other previously published
      studies. The renal clearance and urinary recovery of glucuronidated zidovudine
      was reduced when zidovudine was given in combination with didanosine, possibly
      due to competition for renal tubular secretion. These data suggest that no
      clinically important pharmacokinetic interaction occurs when zidovudine and
      didanosine are given together.

PMID- 8540762
TI  - Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine
      lesioned mouse brain.
AB  - Pergolide, along with bromocriptine and lisuride, is one of the most active
      dopamine receptor agonists. To determine whether or not pergolide protects
      against dopaminergic neuronal damage, via its activity on monoamine metabolism,
      we studied the effects of pergolide pretreatment on changes in monomaines and
      their metabolites in the mouse striatum after intracerebroventricular injection
      of 6-hydroxydopamine with pretreatment of desipramine. After
      intracerebroventricular administration of 6-hydroxydopamine (40 micrograms) in
      mice, the levels of dopamine and its metabolites (DOPAC, HVA) in the striatum
      rapidly decreased to 49%, 29% and 68%, respectively, of the naive controls at
      week 1 but then gradually recovered to control levels at weeks 2 and 4. Repeated
      pretreatment with pergolide (0.5 mg/kg, i.p.) for 7 days before administration of
      6-hydroxydopamine, almost completely protected against reduction in striatal
      dopamine and its metabolites 1 week after injection of 6-hydroxydopamine.
      Therefore, pergolide could normalize the decreased dopamine synthesis or storage,
      and has a neuroprotective effect against dopaminergic dysfunction induced by the
      neurotoxin, 6-hydroxydopamine. Although we found that pergolide did not show
      radical scavenging activity in an in vitro system that generated hydroxyl
      radicals, it has been reported in vivo that pergolide treatment may induce Cu/Zn
      superoxide dismutase in the rat striatum. Considering these findings, pergolide
      may well be protective to dopaminergic neurons, largely because of its effects on
      presynaptic autoreceptors and on its induction of Cu/Zn superoxide dismutase.
      Further research on the neuroprotective effects of pergolide in Parkinson disease
      models, by injection of 6-hydroxydopamine, is needed to clarify its mechanism of
      action on dopaminergic indices.

PMID- 8540763
TI  - Effects of serotoninergic agents on downregulation of beta-adrenoceptors by the
      selective serotonin reuptake inhibitor sertraline.
AB  - The results of the present study show that the down-regulation of beta
      adrenoceptors of rat brain, induced by subacute administration of sertraline, is
      facilitated when this selective serotonin reuptake inhibitor was co-administered
      with the serotonin releaser, norfenfluramine, or the serotonin terminal
      autoreceptor antagonist, methiothepin. The respective drug combination produced a
      reduction in Bmax of [3H]dihydroalprenolol binding to cortical membranes of
      treated rats at a dose of the releaser, release enhancer, or sertraline, which
      was ineffective when administered alone. In a similar manner, the 5-HT1A
      agonists, gepirone and 8-OH-DPAT, were found to facilitate the downregulation of
      beta-adrenoceptors induced by sertraline. The 5-HT1B agonist, 3
      trifluoromethylphenylpiperazine, and the 5-HT2 antagonist, ritanserin, showed
      neither facilitation nor antagonism of sertraline, but the 5-HT3 antagonist,
      ondansetron, attenuated the decrease of Bmax of [3H]dihydroalprenolol binding
      elicited by sertraline. Agents that putatively increase the serotoninergic
      activity facilitated the down-regulation of beta-adrenoceptors induced by
      sertraline, suggesting that the enhancement of serotonin transmission, expected
      of the selective serotonin reuptake inhibitor itself, may play a role in this
      effect of sertraline. Whether the downregulation of brain beta-adrenoceptors by
      sertraline plays any role in its antidepressant activity cannot be deduced from
      these experiments.

PMID- 8540764
TI  - Central cardiovascular effects of CPU-23, a substituted tetrahydroisoquinoline,
      in rats.
AB  - The cardiovascular effects of intracerebroventricular (i.c.v.) injections of low
      doses of CPU-23, a substituted tetrahydroisoquinoline, were investigated and
      compared with those of nifedipine in pentobarbital-anaesthetized Sprague-Dawley
      rats. CPU-23, in doses of 0.2 to 0.5 mg/kg (i.c.v.), which did not elicit any
      significant cardiovascular responses when injected intravenously, caused a clear
      cut and long-lasting decrease of mean arterial pressure (MAP) and heart rate (HR)
      in a dose-dependent manner. The effects of CPU-23, in a dose of 0.05 mg/kg, were
      similar to those of nifedipine, a prototype L-type calcium antagonist. The
      hypotensive effects of CPU-23 were significantly attenuated by bilateral cervical
      vagotomy. The results strongly suggest that a central component may be involved
      in the cardiovascular effects of CPU-23 and that dihydropyridine receptor sites
      in the brain may be involved in the central control of cardiovascular functions.

PMID- 8540765
TI  - Effects of mefloquine on Ca2+ uptake by crude microsomes of rabbit skeletal
      muscle.
AB  - The effects of the antimalarial agent, mefloquine, and its derivatives on Ca2+
      uptake and release by crude microsomes from the rabbit skeletal muscle were
      investigated using a spectrophotometric method. These compounds diminished the
      rate of Ca2+ uptake and inhibited the Ca2+ pump ATPase activity of the
      microsomes. Except for quinine, they appear to have negligible effects on Ca2+
      release channels. Of the compounds investigated, mefloquine had the most
      pronounced effect on Ca2+ uptake and was also the most potent (noncompetitive)
      inhibitor of Ca(2+)-ATPase (Ki: 53 microM). The ability of mefloquine to
      interfere with Ca2+ sequestration into the sarcoplasmic reticulum via inhibition
      of the Ca2+ pump ATPase, may explain some of its actions on the isolated skeletal
      muscle (relaxation, inhibition of twitch responses, diminution of caffeine
      contractures) observed in earlier studies. However, its contractile effects are
      less readily explained. The novel finding that mefloquine inhibits the Ca2+ pump
      ATPase of the skeletal muscle, suggests that it may have similar effects on the
      Ca(2+)-ATPases of other tissues.

PMID- 8540766
TI  - Physiological doses of [Ile5]- and [Val5]-Angiotensin II fail to increase plasma
      catecholamines at the peak pressor response in rats.
AB  - Pressor responses to [Ile5]-Angiotensin II and [Val5]-Angiotensin II were
      measured following single intravenous doses of 0.0075, 0.075, 0.375, 0.75 and 7.5
      micrograms/kg b.w. in anesthetised rats. [Val5]-Angiotensin II was significantly
      (10 per cent) more potent than [Ile5]-angiotensin II when log dose was plotted
      against the increase in carotid arterial pressure. Doses of 0.075 microgram/kg
      b.w. or more of each of the two peptides gave a full pressor response within 30
      seconds. However, only at the highest and, probably, nonphysiological dose of
      [Ile5]-Angiotensin II (7.5 micrograms/kg b.w.) was there a significant increase
      in noradrenaline and adrenaline concentrations measured using a radioenzymatic
      assay. [Val5]-Angiotensin II was more potent than [Ile5]-Angiotensin II insofar
      as plasma noradrenaline increased significantly (p < 0.05) following doses of
      0.75 and 7.5 micrograms/kg b.w.; adrenaline at the higher dose only. Plasma
      dopamine was unresponsive to both peptides.

PMID- 8540767
TI  - Effect of ambrein, a major constituent of ambergris, on masculine sexual behavior
      in rats.
AB  - The effect of ambrein, a major constituent of ambergris, was studied on the
      sexual behavior of male rats. The rats were administered ambrein in doses of 100
      and 300 mg/kg body weight. Male sexual activities were assessed by recording the
      erectile responses (penile erection) and homosexual mountings in the absence of
      female. The copulatory studies were carried out by caging males with receptive
      females brought into estrus with subcutaneous injections of estradiol benzoate
      and progesterone. The copulatory pattern of treated male rats (mountings,
      intromissions, ejaculations and refractory period), the pendiculations
      (yawns/stretches) and orientation activities towards females, the environment and
      themselves, were recorded. Ambrein produced recurrent episodes of penile
      erection, a dose-dependent, vigorous and repetitive increase in intromissions and
      an increased anogenital investigatory behavior, identifying the drug used in the
      present study as a sexual stimulant. It is conceivable from the present results
      that the ambrein-modified masculine sexual behavior in male rats supports the
      folk use of this drug as an aphrodisiac.

PMID- 8540768
TI  - Enhancement of defecation and distal colonic motor activity by KW-5092, a novel
      gastroprokinetic agent, in rats.
AB  - KW-5092 ([1-[2-[[[5-(piperidinomethyl)-2-furanyl]- methyl]amino]ethyl]-2
      imidazolidinylidene]propanedinitrile fumarate) is a novel gastroprokinetic agent
      with acetylcholinesterase inhibitory and acetylcholine release facilitatory
      activity. The present study examined the effects of KW-5092 on the defecation and
      colonic motor activity in rats. KW-5092, at 1 to 30 mg/kg, p.o., dose-dependently
      increased the fecal pellet output. In the in vitro study, KW-5092, at 10(-6) M to
      10(-5) M, evoked contraction of the isolated distal colonic preparation. In the
      in vivo study, KW-5092, at 1 to 10 mg/kg, p.o., induced an increase in the distal
      colonic motor index, which was dose-dependently inhibited by atropine (0.1 to 1
      mg/kg, i.v.). The present results suggest that KW-5092 induces the defecation in
      rats by enhancing the distal colonic motor activity via its acetylcholinesterase
      inhibitory activity and/or acetylcholine release facilitatory activity. KW-5092
      may be a useful drug in the treatment of constipation.

PMID- 8540769
TI  - Furosemide-sensitive K+ transport in transformed and nontransformed rat liver
      epithelial cells: regulation by protein kinase C and involvement in cell growth.
AB  - Using Rb+ as a K+ tracer and atomic absorption spectrophotometry for measuring
      the Rb+ stable isotope, we studied K+ transport systems and their regulation by
      protein kinase C in nontransformed and spontaneously transformed rat liver
      epithelial cells. Ouabain-sensitive Na+/K(+)-ATPase and the furosemide-sensitive
      Na+/K+/Cl- cotransport had comparable activity ratios in both cell types (0.92
      and 1 in nontransformed and transformed rat liver epithelial cells,
      respectively). The protein kinase C activators, dioctanoylglycerol and phorbol
      myristate acetate, partly inhibited the Na+/K+/Cl- cotransport in both cell types
      but their effect was stronger in nontransformed cells, suggesting that, in
      transformed cells, the Na+/K+/Cl- cotransport had partly lost the ability to be
      inhibited by protein kinase C. In both cell types, phorbol myristate acetate had
      little and dioctanoylglycerol had no inhibitory effect on Na+/K(+)-ATPase.
      Furosemide (1 mM) partly inhibited the [3H]thymidine incorporation in both cell
      types, suggesting an involvement of the Na+/K+/Cl- cotransport in rat liver
      epithelial cell growth.

PMID- 8540770
TI  - Hepatoprotective effect of SY-640, a novel acetamide derivative, on
      Propionibacterium acnes and lipopolysaccharide-induced liver injury in mice.
AB  - The hepatoprotective effect of SY-640 on Propionibacterium acnes and
      lipopolysaccharide-induced liver injury in mice and its protective mechanism were
      examined. Oral administration of SY-640, 150 mg/kg once daily for 7 days,
      significantly inhibited Propionibacterium acnes and lipopolysaccharide-induced
      liver injury, but a single administration was without effect. Liver-infiltrating
      cells (T-lymphocytes and macrophages) play an important role in Propionibacterium
      and lipopolysaccharide-induced liver injury and express a higher level of
      leukocyte function-associated antigen-1. SY-640 inhibited the number of liver
      infiltrating cells and attenuated the increased expression of leukocyte function
      associated antigen-1 on these cells. Tumor necrosis factor-alpha mediated
      Propionibacterium acnes and lipopolysaccharide-induced liver injury, and SY-640
      inhibited the elevation of the serum tumor necrosis factor-alpha concentration
      after injection of lipopolysaccharide in Propionibacterium acnes-primed mice. The
      putative effects of SY-640 are inhibitory effects on infiltration into the liver
      and on activation of T-lymphocytes and macrophages after Propionibacterium acnes
      priming, and attenuation of expression of cell adhesion molecules such as
      leukocyte function-associated antigen-1. The immunological effect of SY-640 is
      likely to be closely related to the inhibition of Propionibacterium and
      lipopolysaccharide-induced liver injury.

PMID- 8540771
TI  - Prevention of organophosphate-induced toxicity in mice.
AB  - bis-Quaternary amines, which are acetal analogues of hemicholinium-3, were
      synthesized and several compounds were potent chemicals to antagonize toxicity
      induced by the organophosphate, paraoxon. Structural requirements were specific
      and included two oxygen atoms (bis-acetal substitution) within 6 or 7 atom
      heterocyclic rings, oxygen atoms spaced 2-carbon atoms from the quaternary
      nitrogen, and carbonyl substitutions adjacent to the spacing moieties, either
      bicyclohexyl or biphenyl. Biological testing showed a positive potency
      correlation between the chemicals when data from the following tests were
      compared: antagonism in mice of paraoxon-induced motor impairment using the
      incline screen and toxicity, and ability to induce contractions of guinea-pig
      isolated ilea. The compounds were compared with the often used protective
      antagonist of organophosphate-induced toxicity, pyridostigmine. One compound, MFS
      3, was seven times more efficacious and possessed a much higher therapeutic
      index. Possible mechanisms of action for these chemicals are discussed.

PMID- 8540772
TI  - Neurodevelopmental abnormalities and schizophrenia. A family affair.

PMID- 8540773
TI  - Rhesus incompatibility as a risk factor for schizophrenia in male adults.
AB  - BACKGROUND: Rhesus (Rh) incompatibility is a cause of hemolytic disease of the
      fetus and newborn. Hemolytic disease results from the transplacentally
      transmitted maternal antibodies against Rh factor D and can cause permanent
      neurological damage in the affected newborn. This study examines the hypothesis
      that Rh incompatibility may be a risk factor for schizophrenia. METHODS: A sample
      of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332
      Rh compatible, and compared on rate of schizophrenia. RESULTS: The rate of
      schizophrenia was significantly higher in the Rh-incompatible group (2.1%)
      compared with the Rh-compatible group (0.8%) (P < .03). In addition, since the
      risk for Rh hemolytic disease increases with second and later Rh incompatible
      pregnancies, it is noteworthy that the second- and later-born incompatible
      offspring exhibited a significantly higher rate of schizophrenia than second- and
      later-born compatible offspring (P < .05). Also, as predicted, the rate of
      schizophrenia among firstborn incompatible subjects was not significantly
      different from that of firstborn compatible subjects (1.1% vs 0.7%). CONCLUSION:
      Rh incompatibility may be a risk factor for schizophrenia.

PMID- 8540774
TI  - Schizophrenia after prenatal famine. Further evidence.
AB  - BACKGROUND: Suggestive findings of an earlier study that prenatal nutritional
      deficiency was a determinant of schizophrenia prompted us to undertake a second
      test of the hypothesis using more precise data on both exposure and outcome.
      METHODS: Among persons born in the cities of western Netherlands during 1944
      through 1946, we compared the risk for schizophrenia in those exposed and
      unexposed during early gestation to the Dutch Hunger Winter of 1944/1945. The
      frequency of hospitalized patients with schizophrenia at age 24 to 48 years in
      the exposed and unexposed birth cohorts was ascertained from a national
      psychiatric registry. RESULTS: The most exposed birth cohort, conceived at the
      height of the famine, showed a twofold and statistically significant increase in
      the risk for schizophrenia (relative risk [RR] = 2.0; 95% confidence interval
      [CI] = 1.2 to 3.4; P < .01) in both men (RR = 1.9; 95% CI = 1.0 to 3.7; P = .05)
      and women (RR = 2.2; 95% CI = 1.0 to 4.7; P = .04). Among all birth cohorts of
      1944 through 1946, the risk for schizophrenia clearly peaked in this exposed
      cohort. CONCLUSION: Prenatal nutritional deficiency may play a role in the origin
      of some cases of schizophrenia.

PMID- 8540775
TI  - Search for viral nucleic acid sequences in brain tissues of patients with
      schizophrenia using nested polymerase chain reaction.
AB  - BACKGROUND: We used polymerase chain reaction to search for nucleic acid
      sequences of several viruses in DNA and RNA extracted from brain tissues of
      schizophrenic and control subjects. METHODS: We extracted DNA and RNA templates
      from frozen brain specimens of 31 patients with schizophrenia and 23
      nonschizophrenic control patients with other diseases. The extracts were
      subjected to polymerase chain reaction with oligonucleotide primers for 12
      different viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type
      1, human herpesvirus type 6, varicellazoster virus, measles virus, mumps virus,
      rubella virus, the picornavirus group, influenza A virus, human T-cell
      lymphotropic virus type I, and St Louis encephalitis virus), several of which
      have been suspected of involvement in schizophrenia. Nested primers were used to
      increase the sensitivity of the method. RESULTS: No amplified nucleic acid
      sequences encoded by the selected viral genomes were detected in extracts of any
      brain specimens from either schizophrenic or control patients. CONCLUSIONS: These
      data agree with previous studies that failed to find sequences of a number of
      viruses in the cerebrospinal fluid or selected areas of the brains of
      schizophrenic patients. Additional efforts should be undertaken to identify other
      known and unknown pathogens in schizophrenia, sampling more areas of the brain
      from subjects with a variety of clinical types of schizophrenia.

PMID- 8540776
TI  - Effects of rapid tryptophan depletion in patients with seasonal affective
      disorder in remission after light therapy.
AB  - BACKGROUND: Previous studies show that rapid tryptophan depletion reverses the
      effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs
      in patients with remitted nonseasonal depression. The objective of this study was
      to investigate the effects of rapid tryptophan depletion in patients with
      seasonal affective disorder (SAD) that was in clinical remission after light
      therapy. METHODS: Patients who met DSM-III-R criteria for recurrent major
      depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated
      with a standard course of light therapy. Ten patients with SAD in clinical
      remission after light therapy underwent rapid tryptophan depletion in a placebo
      controlled, double-blind crossover study. Behavioral ratings and plasma
      tryptophan levels were obtained before and after rapid tryptophan depletion.
      RESULTS: Plasma total and free tryptophan levels were significantly reduced to
      20% of normal levels by the rapid tryptophan depletion. The depletion session
      resulted in significant increases in depression scores compared with the sham
      control session. Six of 10 patients had a clinically significant relapse of their
      depression following the tryptophan depletion session. CONCLUSIONS: Rapid
      tryptophan depletion appears to reverse the antidepressant effect of bright light
      therapy in patients with SAD. This suggests that the therapeutic effects of
      bright light in SAD may involve a serotonergic mechanism.

PMID- 8540777
TI  - Seasonal changes in mood and behavior. The role of genetic factors.
AB  - BACKGROUND: Seasonal rhythms in mood and behavior (seasonality) have been
      reported to occur in the general population. Seasonal affective disorder, a
      clinically diagnosed syndrome, is believed to represent the morbid extreme of a
      spectrum of seasonality. Two types of seasonality have been clinically described:
      one characterized by a winter pattern and a second by a summer pattern of
      depressive mood disturbance. METHODS: By using methods of univariate and
      multivariate genetic analysis, we examined the relative contribution of genetic
      and environmental factors to the risk of seasonality symptoms that were assessed
      by a mailed questionnaire of 4639 adult twins from a volunteer-based registry in
      Australia. RESULTS: Seasonality was associated with a winter rather than a summer
      pattern of mood and behavioral change. In each behavioral domain (ie, mood,
      energy, social activity, sleep, appetite, and weight), a significant genetic
      influence on the reporting of seasonal changes was found. Consistent with the
      hypothesis of a seasonal syndrome, genetic effects were found to exert a global
      influence across all behavioral changes, accounting for at least 29% of the
      variance in seasonality in men and women. CONCLUSIONS: There is a tendency for
      seasonal changes in mood and behavior to run in families, especially seasonality
      of the winter type, and this is largely due to a biological predisposition. These
      findings support continuing efforts to understand the role of seasonality in the
      development of mood disorders.

PMID- 8540778
TI  - Anterior paralimbic mediation of procaine-induced emotional and psychosensory
      experiences.
AB  - BACKGROUND: Procaine activates limbic structures in animals. In humans, acute
      intravenous administration of procaine yields emotional and psychosensory
      experiences and temporal lobe fast activity. We studied procaine's acute effects
      on cerebral blood flow (CBF) in relationship to clinical responses. METHODS:
      Cerebral blood flow was assessed by positron emission tomography with oxygen-15
      labeled water in 32 healthy volunteers. Data were analyzed with statistical
      parametric mapping and magnetic resonance imaging-directed regions of interest.
      RESULTS: Procaine increased global CBF and, to a greater extent, anterior
      paralimbic CBF. Subjects with intense procaine-induced fear compared with those
      with euphoria had greater increases in left amygdalar CBF. Absolute and
      normalized left amygdalar CBF changes tended to correlate positively with fear
      and negatively with euphoria intensity. Procaine-induced visual hallucinations
      appeared associated with greater global and occipital CBF increases. Absolute
      occipital CBF increases appeared to correlate positively with visual
      hallucination intensity. CONCLUSIONS: Procaine increased anterior paralimbic CBF,
      and different clinical responses appeared to be associated with different
      patterns of CBF changes.

PMID- 8540779
TI  - High school students who use crack and other drugs.
AB  - BACKGROUND: When it appeared in the 1980s, crack was thought to represent a
      completely new pathway of entry into drug use. Our objective was to identify the
      distinguishing characteristics of adolescents who have reached different stages
      of drug use, in particular the highest state represented by crack. METHODS:
      Adolescents (N = 7611) representative of students in grades 7 to 12 from 53 New
      York state schools were classified in the following six mutually exclusive,
      cumulative categories of drug use: nonusers; alcohol and/or cigarette users only;
      marijuana users only; users of illicit drugs other than marijuana but neither
      cocaine nor crack; cocaine but not crack users; and crack users. The groups were
      compared in level of psychosocial functioning. RESULTS: Students who use illicit
      drugs show deficits in school performance, quality of family relationships, and
      health and increased psychological symptoms. Compared with nonusers, they are
      more delinquent and more actively involved with their peers and live in social
      environments in which the perceived use of drugs by other adolescents and parents
      is more extensive. Delinquency and extent of perceived drug use consistently
      increase with each higher stage of use. Crack users exhibit the lowest level of
      psychosocial functioning of any drug-using group. CONCLUSIONS: There are stage
      specific characteristics and common characteristics (delinquent participation,
      peer drug use) throughout the developmental sequence of drug use. Despite
      declines over the last two decades in the prevalence of the use of different
      drugs, young people who use drugs display characteristics over historical time
      similar to those of young drug users 20 years ago.

PMID- 8540780
TI  - Response of organic catatonia to risperidone.

PMID- 8540781
TI  - Panic attacks: Klein's false suffocation alarm, Taylor and Rachman's data, and
      Ley's dyspneic-fear theory.

PMID- 8540782
TI  - The occurrence of schizophrenia in monozygotic twins and fractal dendritic
      development.

PMID- 8540783
TI  - The 45th annual John Stanley Coulter Lecture. Post-polio sequelae and the
      paradigms of the 50s: Newtie, Ozzie, and Harriet versus paradigms of caring and a
      future for rehabilitation in America.

PMID- 8540784
TI  - Orgasm in women with spinal cord injuries: a laboratory-based assessment.
AB  - OBJECTIVE: To understand the characteristics and physiological sexual responses
      of women with spinal cord injuries (SCI) during orgasm. DESIGN: Controlled
      laboratory-based analysis of women's physiological and subjective responses
      during a single session in which they attempted to perform stimulation to orgasm.
      SETTING: The sexual physiology laboratory at our free-standing rehabilitation
      hospital. PARTICIPANTS: A volunteer sample of 25 women with SCI and 10 able
      bodied control subjects, matched for age. INTERVENTION: A 75-minute protocol
      designed to obtain information on the physiological events accompanying orgasm.
      DEPENDENT VARIABLES: Included vaginal pulse amplitude, heart rate, respiration
      rate, blood pressure, subjective arousal and subscores on the Derogatis Sexual
      Functioning Inventory (DSFI). RESULTS: Data were analyzed both within and across
      neurological groups: complete SCI, incomplete SCI, and able-bodied controls. All
      able-bodied subjects achieved orgasm whereas 52% of SCI subjects achieved orgasm.
      Degree and type of SCI did not significantly relate to subjects' ability to
      achieve orgasm. Subjects with no lower extremity function took significantly
      longer than able-bodied subjects to achieve orgasm. Differences between baseline
      and orgasm readings are described for each of the major physiological measures.
      Results of DSFI revealed that able-bodied subjects acknowledged greater sexual
      satisfaction than SCI subjects. Subjects who achieved orgasm scored higher on
      sexual information and sex drive. CONCLUSION: Results support previous self
      report studies, in that a large percentage of SCI women achieved orgasm
      regardless of pattern or degree of neurological injury. No consistent
      characteristics were identified that would allow prediction of which women with
      SCI would be able to experience orgasm. However, subjects who achieved orgasms
      had a higher sex drive and greater sexual knowledge. Implications for sex therapy
      treatment programs with spinal cord injured women are discussed.

PMID- 8540785
TI  - Functional outcome after rehabilitation for severe traumatic brain injury.
AB  - OBJECTIVE: (1) Define functional status at rehabilitation discharge and follow-up
      for patients admitted with Functional Independence Measure (FIM) of 18 after
      traumatic brain injury; (2) describe patterns of function measured at discharge,
      rehabilitation lengths of stay and costs, and disposition. DESIGN: Retrospective,
      descriptive study using data from the Uniform Data System for Medical
      Rehabilitation (UDSMR) dataset. SETTING: Acute rehabilitation hospitals and, for
      follow-up data, variety of settings, from community to long-term care. PATIENTS:
      328 patients with rehabilitation admission FIM of 18 (principal impairment group
      "Brain Dysfunction, Traumatic") drawn from 5,430 TBI patients entered into the
      data set during 1989-1991. Excluded were 22 persons readmitted to rehab, 5
      deaths, 1 case without recorded disposition, and 49 cases without ICD-9 code
      consistent with brain trauma. MAIN OUTCOME MEASURES: FIM scores at rehab
      discharge and follow-up; disposition; length of stay; cost. RESULTS: (1) Mean FIM
      score at discharge for the group overall (n = 328) was 53 (median = 42 with
      interquartile range of 18 to 87); (2) 7.6% had functional scores consistent with
      independence in motor areas measured by FIM; (3) 2.7% had functional scores
      consistent with independence in cognitive areas measured by FIM; (4) 26.1% showed
      no change in FIM score between admission and discharge; (5) 53% were discharged
      to community settings, 25% to long-term care, 11% to acute facilities, and 11% to
      other rehab facilities; (6) average length of stay in acute rehab was 110 days
      (SD = 70.9, median = 99 days, interquartile range = 57 to 153 days); (7) average
      rehabilitation charges (n = 322) were $110,891; (8) for those with follow-up data
      (n = 59), average FIM score was 79 (median, 90); 24% were in school and 5% worked
      in sheltered workshops. CONCLUSIONS: (1) Even the most severely disabled persons
      admitted to acute rehabilitation after traumatic brain injury can show a large
      degree of measurable functional improvement; (2) while about 25% of patients
      showed no measured FIM change, some showed dramatic degrees of functional
      recovery; (3) most common discharge setting was home (and community).

PMID- 8540787
TI  - A behavioral approach to the treatment of urinary incontinence in a disabled
      population.
AB  - Although the literature has indicated that incontinence can be successfully
      treated with nonsurgical methods in the able-bodied population, there has been
      little research performed in the disabled population. Fifty-four patients with
      various disabilities were treated with pelvic muscle exercises, using biofeedback
      in conjunction with adjustments in their bowel program, caffeine intake, fluid
      intake, toileting schedules, transfer training, and medications. The average
      number of incontinent episodes before intervention was 3.6 per day, which was
      reduced to 0.8 per day after interventions (p < .001). The characteristics
      associated with treatment success and failure were evaluated and are discussed in
      this article, In addition, the change in amplitude and duration of the pelvic
      muscle surface electromyograph were analyzed. A statistical trend (p = .07) was
      discovered between an increase in amplitude and a positive outcome. There was a
      statistical association between increased pelvic floor contraction duration and a
      good or excellent outcome (p < .05). In conclusion, a behavioral approach to
      treatment of urinary incontinence is efficacious in the disabled population who
      can volitionally void and can voluntarily contract their pelvic muscles.

PMID- 8540786
TI  - Explaining quality of life for persons with traumatic brain injuries 2 years
      after injury.
AB  - OBJECTIVE: To model the complex effects of demographic, psychosocial, physical,
      and rehabilitation variables on quality of life 2 years after hospital discharge.
      DESIGN: Medical record and longitudinal survey data on traumatic brain injury
      (TBI) survivors who did or did not receive formal rehabilitation services after
      being injured were analyzed. SETTING: The study sample was selected from a
      representative sample of hospitals in north-central Alabama. PARTICIPANTS:
      Criteria for inclusion were: (1) 18 years and older with TBI; (2) discharged
      after hospital stay of 3 or more days; and (3) resided and injured in Alabama.
      There were 293 persons eligible for the 24-month follow-up survey, 186 (63%) of
      whom participated; the focus was on the 116 persons (of 186) who responded to the
      surveys themselves. MAIN OUTCOME MEASURE: A causal model of hypothesized direct
      and indirect effects of several variables on quality of life outcomes. RESULTS:
      Employment was the strongest contributor of improved quality of life. Persons
      unable to pay for health care showed less improvement in functional independence
      12 to 24 months postinjury and reported a poorer quality of life. The
      psychosocial variables of self-blame and family support improved quality of life
      by reducing impairments and increasing the likelihood of employment. Family
      support also improved quality of life by increasing functional independence.
      Fewer physical impairments and gains in functional independence directly improved
      quality of life. CONCLUSION: The interrelationships between psychosocial and
      physical variables are important when examining quality of life. Interventions
      are recommended targeting psychosocial variables and functional independence in
      efforts to improve quality of life.

PMID- 8540788
TI  - Upper extremity performance test for the elderly (TEMPA): normative data and
      correlates with sensorimotor parameters. Test d'Evaluation des Membres Superieurs
      de Personnes Agees.
AB  - OBJECTIVES: Objectives of this study were to develop normative data for the Test
      d'Evaluation des Membres Superieurs de Personnes Agees (TEMPA) and determine its
      relation to upper extremity sensorimotor parameters such as fine and gross
      dexterity, coordination, strength, endurance, range of motion, and several types
      of sensibility. DESIGN: Cross-sectional study. SETTING: Community-dwelling
      subjects. PARTICIPANTS: Three hundred sixty healthy subjects randomly recruited
      by age and sex strata (60 to 69, 70 to 79, and 80 or older). MAIN OUTCOME
      MEASURES: Length of execution of the tasks in the TEMPA. RESULTS: Normative data
      are reported by gender and age group. The time taken to execute the tasks
      increased significantly with age. The women were faster on the tasks requiring a
      higher degree of fine dexterity, whereas the task requiring a lesser degree of
      fine dexterity and sensibility and more grip strength was accomplished faster by
      the men. Subjects who were more active and described themselves as being in
      excellent or good health performed better. CONCLUSION: The norms will help
      clinicians differentiate better between normal and pathological aging in upper
      extremity performance.

PMID- 8540789
TI  - Swallow management in patients on an acute stroke pathway: quality is cost
      effective.
AB  - OBJECTIVE: To assess the effects of swallowing management in patients with acute
      nonhemorrhagic stroke placed on a clinical pathway, and to evaluate whether
      swallow function on admission can be used as a predictor of length of stay (LOS)
      and outcome disposition. DESIGN: Intervention study to reduce complications of
      dysphagia in patients with acute stroke. SETTING: Urban community hospital.
      PATIENTS: Data were collected on 124 patients with acute nonhemorrhagic stroke
      admitted from January to December 1993. INTERVENTIONS: A swallow screen was
      completed within one day of admission and before any oral intake. MAIN OUTCOME
      MEASURES: Dysphagia and functional independence measure (FIM) scores on
      admission, occurrence of aspiration pneumonia, LOS, outcome disposition and cost
      effectiveness analysis. RESULTS: Thirty-nine percent of all patients (p < .05)
      failed the initial swallow screen and required altered dietary texture and
      intervention. No patients developed aspiration pneumonia. Of those with
      dysphagia, 21% recovered intact swallowing by discharge; 19% required gastrostomy
      tube placement. Patients with dysphagia had lower admission FIM scores than
      nondysphagia patients. The LOS was longer for the dysphagia group (8.4 +/- 0.9
      days) compared with patients without dysphagia (6.4 +/- 0.6 days, p < .05).
      Patients with dysphagia were less likely to be discharged to home (27%) than were
      nondysphagia patients (55%), and twice as likely to be discharged to a nursing
      home (p < .05). CONCLUSIONS: This study demonstrates that early swallow screening
      and dysphagia management in patients with acute stroke reduces the risk of
      aspiration pneumonia, is cost effective, and assures quality care with optimal
      outcome.

PMID- 8540790
TI  - High-voltage galvanic stimulation on wound healing in guinea pigs: longer-term
      effects.
AB  - The purpose of this investigation was to determine the effects of high-voltage
      stimulation (HVS) on wound tensile strength properties and wound closure
      (histology). Eighteen mature guinea pigs with full-thickness incisions were
      treated with HVS for 45 minutes daily for 2 weeks; 9 animals were studied after
      the 14 days of treatment and the remaining 9 were studied 2 weeks later. Five
      animals (10 wounds) served as controls at each time period. After 2 or 4 weeks,
      treated and untreated skin was harvested, tested to failure, and prepared for
      histological examination. Two-week-treated and control wounds had comparable
      values for peak force to failure, elongation, and energy absorbed to failure.
      Epithelialization was more advanced in treated animals at 14 days (p < .05).
      There was a trend (p = .068) toward stronger wounds in 4-week-treated animals
      (maximum load to failure), but not differences were observed between controls and
      treated groups for elongation or energy absorbed to failure. Dermal healing
      appeared to be more advanced in treated animals at 30 days. Although peak force
      to failure was almost 500g higher for treated guinea pigs after 2 weeks of
      treatment and more than 700g higher than controls after 4 weeks, mean data were
      highly variable, so the hypothesis that HVS augments wound strength could not be
      accepted. It is difficult, however, not to assign clinical significance to the
      findings.

PMID- 8540791
TI  - Ankle inversion injury and hypermobility: effect on hip and ankle muscle
      electromyography onset latency.
AB  - OBJECTIVE: Changes in reflexes associated with chronically sprained ankles were
      examined by measuring the reflex response latency of hip and ankle muscles during
      instantaneous ankle/foot inversion. DESIGN: Randomized trials. SETTING: All
      studies were performed in the Research Department laboratories at a major
      rehabilitation center in a large metropolitan area. PATIENTS AND OTHER
      PARTICIPANTS: Twenty subjects were assigned to 2 groups (normal and hypermobile)
      based on goniometry testing. Subjects were recruited from hospital and University
      staff and had a mean age of 31 +/- 5 years. OUTCOME MEASURES: Subjects stood on a
      platform constructed such that either foot/ankle could be instantaneously
      inverted. Latency was measured by EMG surface electrodes placed over the right
      and left gluteus medius and peroneal muscles. Two-factor analysis of variance was
      calculated to determine significant muscle onset latency differences (p < .01)
      between groups. RESULTS: Significant EMG latency differences were found in
      comparing right gluteus medius of the hypermobile group (127.35 +/- 6.02msec)
      with the normal group (150.49 +/- 6.49msec) during right ankle perturbation, and
      the left gluteus medius of the hypermobile group (120.71 +/- 6.16msec) with the
      normal group (136.24 +/- 5.88msec) during left ankle perturbation. CONCLUSIONS:
      These data suggest that there is decreased latency of hip muscle activation after
      ankle inversion in the hypermobile population. In treating ankle instability,
      clinicians must decide to address the altered hip muscle recruitment pattern or
      accept this recruitment pattern as an injury-adaptive strategy and thus accept
      unknown long-term consequences of premature muscle activation (ie, possible
      articular predisposition to degenerative changes, altered joint reaction forces,
      and muscle imbalances).

PMID- 8540793
TI  - Dimensionality and hierarchical structure of disability measurement.
AB  - Since the D-code of the International Classification of Impairments,
      Disabilities, and Handicaps (ICIDH) in its full form has proven to be
      impractical, an instrument based on a selection of 28 items is used to measure
      disability in Dutch patients undergoing rehabilitation. The items are categorized
      into 5 domains of physical, activities of daily living (ADL), social,
      psychological, and communicative activity. Measurement is made on a 4-point scale
      ranging from 0 (not disabled) to 3 (severely disabled). As a result of the
      ordinal character of the rating, statistical and mathematical manipulations of
      the scores are complicated. The aim of this study was to obtain more insight in
      the dimensionality and hierarchical structure of the items, to overcome problems
      in comparing disability between items, between patients, and within patients
      between different moments in time. Mokken scale analysis of the disability scores
      from 1,967 rehabilitation inpatients showed that the 28 items constitute
      hierarchical scales. However, categorization of the items into the 5 original
      domains was not replicated. Five other scales or dimensions were investigated,
      measuring the level of extended ADL, extended psychological, fine motoric,
      work/leisure, and hearing/seeing activity, respectively. The number of items per
      dimension ranges from 14 in the extended ADL dimension to 2 each in the
      work/leisure and hearing/seeing dimensions. Although each disability item may be
      of importance in clinical case management, a reduced set of extended ADL items
      suffices to describe the disability level in this dimension for epidemiological
      research purposes. The other dimensions need further specification to provide
      reliable and sensitive measuring of disability.

PMID- 8540792
TI  - Differences between persons with right or left cerebral vascular accident on the
      Assessment of Motor and Process Skills.
AB  - OBJECTIVE: Persons with right and left cerebral vascular accident (RCVA and LCVA)
      differ in terms of discrete impairments, but there is limited information with
      regard to how such impairments translate into differences in disability. The
      following hypotheses were tested: (1) persons with stroke have lower instrumental
      or domestic activities of daily living (IADL) ability than do matched nondisabled
      controls, (2) persons with RCVA do not differ from persons with LCVA in IADL
      ability, and (3) persons with RCVA and LCVA differ in specific motor and process
      skills that affect IADL performance. DESIGN: Descriptive comparison. SETTING:
      Subjects were tested in settings where rehabilitation services were received
      (home or clinic). SUBJECTS: 71 persons with RCVA, 76 persons with LCVA, and 83
      community-living nondisabled individuals drawn from the Assessment of Motor and
      Process Skills (AMPS) database, matched for age, gender, and number of tasks
      performed. MAIN OUTCOME MEASURE: AMPS, designed to measure type and severity of
      impairments manifested in the context of IADL performance. The AMPS was
      administered to all subjects in accordance with standardized testing procedures.
      RESULTS: The two stroke groups did not differ significantly in IADL ability, but
      both stroke groups had significantly lower IADL performance than did the
      nondisabled subjects. On the AMPS motor scale, persons with RCVA demonstrated
      greater impairment in pacing, transporting, and coordinating two body parts.
      Persons with LCVA demonstrated greater impairments in calibrating movements. No
      differences were found between the two groups in AMPS process skills.
      CONCLUSIONS: Persons with RCVA and LCVA have hemisphere-specific differences in
      motor impairments, but do not differ significantly in IADL ability.

PMID- 8540794
TI  - Lightweight, modular knee-ankle-foot orthosis for Duchenne muscular dystrophy:
      design, development, and evaluation.
AB  - OBJECTIVE: The study aimed to design and construct a modular system of knee-ankle
      foot orthotics (KAFOs) that could be quickly and easily assembled and provided to
      children with Duchenne muscular dystrophy. A pilot study would then compare the
      modular orthotics with the childrens' existing devices. DESIGN: Measurements from
      the legs of a consecutive sample of 26 Duchenne boys were taken to determine the
      sizing of the modular system. Nine boys with Duchenne muscular dystrophy were
      randomly selected to take part in a pilot study that focused on a comparison
      between their original and modular KAFOs of supply time, weight, energy
      expenditure during gait, gait speed, and ease of don/doff. SETTING: The supply
      and fitting of the KAFOs can be done either in the hospital, clinic, or school.
      PATIENTS: Boys with Duchenne muscular dystrophy, referred by the clinician for
      provision of KAFOs. Nine boys were approached to take part in the pilot study;
      all accepted. Their age range was 5 to 13 years. MAIN OUTCOME MEASURES: It is
      possible, by use of a modular KAFO system, to provide long leg orthoses to boys
      with Duchenne muscular dystrophy in approximately 1 hour. RESULTS: The pilot
      study also showed that the modular KAFOs provided a 23% weight saving, resulting
      in a 10% energy saving during ambulation and an 8% increase in walking speed.
      They were easier to don/doff and were preferred by all involved.

PMID- 8540795
TI  - Case-mix measurement in medical rehabilitation.
AB  - Case-mix measurement offers a way to take patient characteristics into account in
      the determination of payment rates. This article begins with an overview of major
      case-mix measures across inpatient hospital and other institutional settings and
      describes ways to measure the suitability and relative strengths of these
      measures. It then briefly discusses issues of payment and the appropriateness of
      alternative case-mix measures to inpatient rehabilitation. The literature review
      extends back to the 1970s, thus preceding advent of the Diagnosis-Related Groups,
      which was the first major case-mix measure developed and implemented in a
      hospital setting.

PMID- 8540796
TI  - Lyme disease presenting as isolated acute urinary retention caused by transverse
      myelitis: an electrophysiological and urodynamical study.
AB  - Several neurological manifestations of Lyme disease, both central and peripheral,
      have been described. Reported here is a case of acute transverse myelitis related
      to a Lyme neuroborreliosis that presented with isolated acute urinary retention
      and no lower-extremity impairment. This case, documented by urodynamic and
      electrophysiological investigations, partially resolved after 6 weeks of
      intravenous ceftriaxone, affording the removal of the indwelling catheter. Alpha
      blocker therapy was needed for 3 months, until the complete normalisation of
      urodynamic and electrophysiological records. This case study indicates that
      whenever urinary retention is encountered associated with acute transverse
      myelitis or alone, the patient should be investigated for Lyme disease.

PMID- 8540797
TI  - Methods for estimating the proper length of a cane.
AB  - OBJECTIVE: To find a practical method of cane length measurement that achieves
      the elbow flexion of 20 degrees to 30 degrees. DESIGN: Two standard methods of
      cane length measurements were compared. Method I: Length of the cane measured
      from the floor to the top of the greater trochanter. Method II: Length of the
      cane measured from the floor to the distal wrist crease. Using an adjustable
      cane, each individual was fitted according to the two methods, and elbow angle
      was measured after each adjustment. Cane length was also correlated with arm
      length and height. PARTICIPANTS: Fifty-two normal volunteers who were ambulatory
      without assistive devices. RESULTS: Mean +/- SD of the elbow angle according to
      Method I and Method II was 44.8 +/- 11.8 and 25.4 +/- 6.1, respectively. A
      significant difference was found in the elbow angle between the two methods
      (unpaired two-tailed student t test, p = 5.910(-18)). Of the 52 volunteers, 4
      (7.7%) measured according to method I and 49 (94.3%) measured according to method
      II showed the elbow angle between 20 degrees and 30 degrees. The ideal length of
      the cane (L) also can be determined by the formula L = H x .45 + .87 meters or A
      x .76 + .19 meters, where H is the height of the individual in meters and A is
      the arm length measured in meters. CONCLUSION: Ideally, cane length should be
      measured from the floor to the distal wrist crease. The length can also be
      determined using the above formulae.

PMID- 8540798
TI  - Neurobiology of depressive symptoms.

PMID- 8540799
TI  - [Bacterial growth in the small intestine].

PMID- 8540800
TI  - [The role of cutaneous electrogastrography in the research of gastric motor
      dysfunction].

PMID- 8540801
TI  - [Hepatic changes in patients with nonspecific ulcerative colitis].
AB  - The presence of hepatic changes in ulcerative colitis ranges from 4.7% to 90% and
      the mechanisms are not clear. This study had the purpose to verify their
      frequency, observe the relation between clinical forms and hepatic lesions and
      identify the possible histological changes in the liver. We studied 21 patients
      with ulcerative colitis (Group 1, subdivided in Group 1A non-alcoholic and 1B
      alcoholic) and compared with 10 patients with irritable bowel syndrome (Group 2).
      The study involved clinical evaluation, ultrasonography liver function tests and
      needle biopsy of the liver, performed by laparoscopy, when necessary. Clinical
      alterations were present in three patients. The ultra-sonographic study was
      altered in 14.3% in Group 1A and in 57.1% in Group 1B. The albumin and
      cholinesterase levels were the most frequent abnormality in ulcerative colitis.
      In irritable bowel syndrome (Group 2), these exams were normal. Liver biopsy was
      performed in 15 patients and variable degrees of histologic changes were present
      in all.

PMID- 8540802
TI  - [Myoelectric gastric activity using cutaneous electrogastrography-
      electrogastrogram].
AB  - Cutaneous electrogastrography was performed in nine healthy volunteers and in 43
      patients presenting with various clinical conditions known to be associated with
      gastric motor disorders, including: 24 with functional dyspepsia, nine with
      longstanding diabetes mellitus, five with recent nausea/vomiting, three with
      pyloric stenosis, one with post-vagotomy gastroparesis, and one with idiopathic
      gastric distension and atony. The electrogastrography signal was recorded during
      1h pre-prandial period and 1h after eating. The electrogastrography dominant
      frequency and power were determined using running spectral frequency analysis and
      the time-course of electrogastrography was evaluated in a pseudo three
      dimensional graphic. The electrogastrography dominant frequency was divided into
      four bands: 1. Bradygastria (0-2.4 cpm); 2. Normal (2.4-3.9 cpm); 3. Tachygastria
      (4.0-9.9 cpm); 4. Duod-resp (10.0-15.0 cpm). The percentage of the dominant
      electrogastrography power into those four frequency bands was determined.
      Electrogastrography was considered normal if functional dyspepsia was normal in
      more than 65% of the time. The electrogastrography was normal (dominant frequency
      into 3 cpm range in > 65%) in: 9/9 healthy volunteers, 3/3 pyloric stenosis, 4/5
      nausea/vomiting, 3/9 diabetes mellitus, 13/24 functional dyspepsia. Gastric
      dysrhythmias were present in > 35% of the electrogastrography recording in: 1/5
      nausea/vomiting, 11/24 functional dyspepsia, 6/9 diabetes mellitus, 1/1 post
      vagotomy gastroparesis, 1/1 gastric distension and atony. Persistent tachygastria
      (> 10%) was found in: 1/1 gastric distension and atony (90% electrogastrography),
      1/1 post-vagotomy gastroparesis, 1/5 nausea/vomiting, 6/9 diabetes mellitus, 6/24
      functional dyspepsia. It was concluded that electrogastrography is a non
      invasive, well-tolerated, reliable means of recording gastric myoelectric
      activity and gastric dysrhythmias. Patients presenting with gastric motor
      disorders, with chronic dyspeptic symptoms, or acute nausea may present
      transitory or persistent gastric dysrhythmias.

PMID- 8540803
TI  - [Watermelon stomach and gastric carcinoid tumor in a cirrhotic patient].
AB  - Gastric antral vascular ectasia or watermelon stomach is a rare but important
      cause of upper gastrointestinal bleeding. The authors report the first case of
      gastric antral vascular ectasia associated with a gastric carcinoid in a
      cirrhotic patient. The article provides a literature review with emphasis on
      etiology, endoscopic features and treatment of this entity.

PMID- 8540804
TI  - [Small bowel bacterial overgrowth syndrome in chagasic megajejunum: report of 2
      cases].
AB  - We report two cases of Chagas' disease with megacolon who presented with chronic
      diarrhea. One of the patients also had evidence of malabsorption, such as
      steatorrhea and hypocalcemia. Barium meal follow-through showed remarkable
      dilation of the jejunum in both cases and, in one of them, an associated
      megaduodenum. Manometric studies of gastrointestinal motility showed abnormally
      slow propagation of the interdigestive migrating motor complex, which was also
      excessively prolonged. Cultivation of jejunal aspirates revealed strict anaerobic
      bacterial growth in both cases. Oral antibiotic therapy led to substantial
      improvement in symptoms. The two cases herein reported indicate that clinical
      manifestations of small bowel bacterial overgrowth, possibly caused by motor
      disturbances associated with megajejunum, may occasionally include the clinical
      picture of gastrointestinal involvement in Chagas' disease.

PMID- 8540805
TI  - [Immunologic changes in alcoholic liver cirrhosis].
AB  - The alcoholic liver cirrhosis usually causes overall immunological changes which
      might be attributed to either the hepatic disease itself, to ethanol action
      and/or to malnourishment of the patient. These immune abnormalities comprise both
      cellular and humoral immunity, consisting of increased immunoglobulin levels,
      depressed late-skin response to antigens, lowered proliferative response of
      lymphocytes to mitogens, lower plasma levels of complement proteins (C3 and C4)
      and by either lower (IL2 and gamma IF) or increased (IL1, TNF, IL6 and IL8)
      cytokine levels. Parallel to the systemic immune suppression found in most
      patients, there is also a concomitant local, genetically based, immune
      stimulation at the liver level which leads to hepatic self-aggression. The
      systemic immune-suppression could be responsible for periodical infections or
      neoplasia found in these patients. The possible factors for the immune exhaustion
      are: a) lower hepatic clearance of toxins and/or bacteria; b) lower hepatic
      synthesis of complement components; c) cytokines (IL2 and gamma IF) deficiencies,
      and d) deficiencies of nutrients related to the antioxidant and/or immune defense
      mechanisms. The immune stimulation of the liver self aggression is characterized
      by the preferential migration of cytotoxic T cell and neutrophils to the liver,
      following stimulatory factors such as Mallory bodies, acetaldehyde and/or
      antibodies. Moreover, the local increase of cytokines (IL1, TNF, IL6 and IL8)
      levels would be liable for the local phagocyte chemotaxy (IL8) or part of liver
      injury (TNF) eased by the lower antioxidant defense of the cirrhotic
      liver.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8540806
TI  - [Excretion of 99m Tc-DISIDA through the bile ducts in the etiological diagnosis
      of neonatal cholestasis].
AB  - We evaluated 51 tests of 99mTc-DISIDA excretion by the biliary tree in patients
      with neonatal cholestasis. The aim of the present study was to verify the value
      of this test in the differentiation of this syndrome, correlating it to the
      clinical and laboratory data. The case studied were divided into two groups:
      extrahepatic biliary atresia, 26 patients (50.9%) and no-extrahepatic biliary
      atresia, 25 patients (49.1%). Analyzing the results, we concluded that this test
      had 96% sensitivity, 56% specificity, 69% positive predictive value, 93% negative
      predictive value and 76.5% accuracy. The accuracy of this test was only lower
      than that of hepatic biopsy. We conclude that the hepatobiliary scintigraphy was
      very useful in the definition of extrahepatic biliary atresia, with less value in
      the group of neonatal hepatitis, perhaps due to the delayed referral of the
      patients, short time of the scintigraphy study or factors related to the etiology
      of cholestasis itself.

PMID- 8540807
TI  - [Small bowel morphometry in acute and persistent diarrhea due to classic
      enteropathogenic Escherichia coli].
AB  - Enteropathogenic E.coli infection may cause different ranges of abnormalities in
      the small bowel villi, but there are no morphometric studies about it. Thirty
      specimens of small intestinal mucosa obtained from children having acute or
      persistent diarrhea by enteropathogenic E.coli were analysed and then compared to
      the specimens of the small intestinal biopsy of thirteen patients of the control
      group. We had the following target in this paper: evaluate the morphological
      changes of intestinal mucosa using linear morphometry and to verify the number of
      intra-epithelial lymphocytes/100 enterocytes; search the presence of Gram
      negative bacteria adhered to the small intestinal mucosa. Gram negative bacteria
      were present in three patients with acute diarrhea. The morphometric changes were
      more remarkable in the villosites which were shorter, in the enteropathogenic
      E.coli group. The total mucosa thickness as well as the villous height and the
      relation villous/crypt were significantly shorter in the enteropathogenic E.coli
      group when compared to the control Group. There were no differences between the
      two groups for the crypt length and for de number of intraepithelial
      lymphocytes/100 enterocytes.

PMID- 8540808
TI  - [Biological versus artificial intelligence: a critical approach].
AB  - After brief considerations about intelligence, a comparative study between
      biologic and artificial intelligence is made. The specialists in Artificial
      Intelligence found that intelligence is purely a matter of physical symbol
      manipulation. The enterprise of Artificial Intelligence aims to understand what
      we might call Brain Intelligence in terms of concepts and techniques of
      engineering. However the philosophers believed that computer-machine can have
      syntax, but can never have semantics. In other words, that they can follow rules,
      such as those of arithmetic or grammar, but not understand what to us are
      meanings of symbols, such as words. In the present paper it is stressed that
      brain/mind complex constitutes a monolithic systemic that functions with emergent
      properties at several levels of hierarchical organization. These hierarchical
      levels are non-reducible to one another. They are at least three (neuronal,
      functional, and semantic), and they function within an interactional plan. The
      brain/mind complex, which transform informations in meanings, deals with problems
      by means of both logical and non-logical mechanisms; while logic allows the mind
      to arrange the elements for reasoning, the non-logical mechanisms (fuzzy logic,
      heuristics, insights) allows the mind to develop strategies to find solutions.
      The model for construction of the "intelligent machine" is the operating way of
      the brain/mind complex, which does not always use logical processes. The role of
      information science in Artificial Intelligence is to search for knowledge itself
      (virtual knowledge), rather than to simply attempt a logico-mathematical
      formalization of knowledge.

PMID- 8540809
TI  - [Single photon emission tomography in temporal epilepsy: interictal and ictal
      studies with visual and semi quantitative analysis].
AB  - Single photon emission tomography (SPECT) was performed in 27 patients with
      refractory complex partial seizures from the temporal lobes due to mesial
      temporal sclerosis. Independent blinded observers assessed the 28 interictal
      studies and 9 ictal/postictal studies. Visual analysis of interictal studies
      detected hypoperfusion in 22, ipsilateral to the epileptogenic zone in 19 (67%)
      and contralateral in 3 (10.7%). Quantified temporal lobe asymmetry, greater than
      a previously derived normal range, correctly identified the epileptogenic zone in
      16 (61.5%) with false lateralization in 4 (15.3%). In all 9 cases in which they
      were performed, ictal/postictal studies showed hyperperfusion at the region of
      epileptic focus. In 3 patients with complex partial seizures followed by
      symmetric generalized tonic-clonic seizures, hyperperfusion restricted to the
      temporal lobe was demonstrated. In 5 of these patients the interical studies were
      unable to demonstrate localized changes. There were no significant correlations
      between SPECT findings and clinical parameters or EEG slowing in the temporal
      lobes.

PMID- 8540810
TI  - [Electroencephalographic evolution in women with refractory epilepsy].
AB  - We reviewed 444 EEGs of 62 women with medically refractory epilepsy, followed up
      for at least 5 years and that had 5 or more EEGs. According to our definitions we
      found 18 patients (29%) with frequent seizures, 16 (25.8%) with very frequent
      seizures, 16 (25.8%) with controlled seizures and 12 (19.3%) with occasional
      seizures. Four patients (6.5%) always showed normal EEGs, 30 (48.4%) had normal
      and abnormal EEGs and 28 (45.2%) only abnormal EEGs. Among the patients who had
      only normal EEGs, two had all seizures controlled, one had occasional seizures
      and one had frequent seizures. Among the patients who had normal and abnormal
      EEGs, 10 had controlled seizures, 5 had occasional seizures, 9 had frequent
      seizures and 6 had very frequent seizures. In the group of patients with always
      abnormal EEGs, 4 had controlled seizures, 6 had occasional seizures, 8 had
      frequent seizures, and 10 had very frequent seizures. In relation to the last
      EEG, it was normal in 7 (43.7%) of 16 patients with controlled seizures, in 3
      (25%) of 12 patients with occasional seizures and in 7 (38.9%) of 18 patients
      with frequent seizures, and in none of the patients with very frequent seizures.
      The patients who had only normal EEGs seem to have a better outcome than those
      with abnormal EEGs. We observed that the last EEG was normal in 43.7% of the
      patients with controlled seizures. These data may suggest a relative importance
      of the EEG considering the long-term prognosis regarding seizure control.

PMID- 8540811
TI  - Highlighting intracranial pressure monitoring in patients with severe acute brain
      trauma.
AB  - Intracranial pressure (ICP) monitoring was carried out in 100 patients with
      severe acute brain trauma, primarily by means of a subarachnoid catheter.
      Statistical associations were evaluated between maximum ICP values and: 1)
      Glasgow Coma Scale (GCS) scores; 2) findings on computed tomography (CT) scans of
      the head; and 3) mortality. A significant association was found between low GCS
      scores (3 to 5) and high ICP levels, as well as between focal lesions on CT scans
      and elevated ICP. Mortality was significantly higher in patients with ICP > 40 mm
      Hg than in those with ICP < or = 20 mm Hg.

PMID- 8540812
TI  - The correlation of CT findings and in-hospital mortality after cerebral
      infarction.
AB  - OBJECTIVE: To evaluate whether findings on computed tomography (CT) are useful to
      predict early mortality after acute cerebral infarction. METHODS: An admission CT
      was performed in 98 patients with disease-onset within 7 days; CT findings were
      analyzed using a checking list; their influence on hospital mortality was studied
      by logistic regression analysis. RESULTS: There were 29 hospital deaths. Uncal
      herniation and midline shift > 4 mm were strongly correlated with fatal outcome.
      Also associated with increased mortality: infarction of a whole hemisphere or in
      the distribution of internal carotid artery; massive (> 90% expected area)
      infarction in the territory of the anterior or posterior cerebral arteries;
      massive or submassive (> 50% expected area) middle cerebral artery infarction;
      large lesion volume (death in 9/13 patients with lesions > 50cm3); any degree of
      mass effect. In 68 patients with single middle cerebral artery lesions, extension
      of the lesion to adjacent vascular territories was also associated with a worse
      outcome. The number of lesions and the presence of contrast enhancement,
      hemorrhagic changes or cerebral atrophy did not influence outcome. CONCLUSIONS:
      CT findings indicating significant mass effect and large infarcts are associated
      with mortality after ischemic stroke. The best combination of clinical and CT
      variables to estimate death risk in individual patients remains to be determined.

PMID- 8540814
TI  - Plasmapheresis as preparatory method for thymectomy in myasthenia gravis.
AB  - To study the effects of plasmapheresis in preparation for thymectomy, two groups
      of 40 patients were selected from a sample of 286 patients with myasthenia gravis
      examined by the first author Group 1 included patients (15 male and 25 female;
      age range 8-64 yrs) who underwent thymectomy without previous plasmapheresis,
      whereas patients in group 2 (17 male and 23 female; age range 11-61 yrs) were
      thymectomized after plasmapheresis. We required patients to have a minimum follow
      up period of 12 months to be included in the study. A clinical evaluation
      protocol composed of 76 items was developed for the study. We found significant
      improvement in respiratory function and muscular strength in patients
      thymetomized after plasmapheresis. Furthermore, the combined treatment reduced
      cost and length of hospital stay. Therefore, we conclude that plasmapheresis
      should be considered as a coadjuvant to thymectomy in the treatment of myasthenia
      gravis.

PMID- 8540813
TI  - [Botulinum toxin in blepharospasm, in hemifacial spasm, and in cervical dystonia:
      results in 33 patients].
AB  - The effects of botulinum toxin type A were studied in 33 patients with dystonia
      (12 blepharospasms, 10 hemifacial spasms and 11 spasmodic torticollis). A rate
      scale was used to evaluate the severity of the dystonic movements, before and two
      weeks after each injection. Among blepharospasm patients, eight were female and
      four were male; the mean age was 57.7 years; the mean time of the disease
      duration was four years. Three had familial history for similar disease; nine
      were essential and three had used neuroleptic drugs (tardive dystonia). The mean
      dose used was 51.3 U, with a mean time of beneficial effects of 2.8 months. For
      22 injections and reinjections, 14 (63.7%) showed an excellent result, five
      (22.7%) good and three (13.6%) null. In the hemifacial spasm group, eight were
      female and two male; the mean age was 52.6 years; the mean time of the disease
      duration was 7.4 years; eight were essential and two post-paralytic. The mean
      dose used was 32 U. From the total of 15 injections and reinjections, all of them
      (100%) had an excellent result, with a mean time of beneficial effect of 3.4
      months. Among the cervical dystonic patients, eight were male and three female;
      the mean age was 44.2 years; the mean time of the disease duration was 12.2
      years; six had essential dystonia, three had used neuroleptic drugs and two had
      familial history for similar disease. The mean dose used was 238.6 U, with the
      mean duration of effect of 3.5 months. From the total of 20 injections and
      reinjections, 18 (90%) had good result, one (5%) mild and one (5%) null.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8540815
TI  - Immunohistochemical alterations of dystrophin in congenital muscular dystrophy.
AB  - The dystrophin distribution in the plasma muscle membrane using
      immunohystochemistry was studied in 22 children with congenital muscular
      dystrophy. The dystrophin was detected by immunofluorescence in muscle biopsy
      through a polyclonal antibody. All the cases had patchy interruptions of the
      fluorescence in the plasma membrane. A large patchy interruption of the
      sarcolemma was found in 17 cases, small interruption in 12, and a combination of
      large and small patchy discontinuity in 7. Small gaps around the fiber like a
      rosary were found in 15 cases. The frequency of these abnormalities ranged cases
      from: all fibers in 5 cases, frequent in 8, occasional in 5, and rare in 4. Five
      cases had total absence of immunofluorescence. These results suggest that the
      dystrophin expression is abnormal in this group of children and that this type of
      abnormalities can not be differentiated from early Becker muscular dystrophy nor
      childhood autosomal recessive muscular dystrophy through immunohystochemistry
      alone.

PMID- 8540816
TI  - [Orofacial evaluation with a punctuation scale in patients with myotonic
      dystrophy (Steinert's disease)].
AB  - Orofacial examination was applied in 39 patients with myotonic dystrophy. We made
      an original table with a scale of punctuation. The group showed a deficit of
      43.70%. The female group was 6.16% better than male's. The maternal inherited
      cases were 3.63% better than the paternal ones. When we separated the groups by
      decades, there was a tendency to an increasingly better performance as the age of
      the beggining of symptoms was later. The performance was 10.68% better in the
      group of patients with 1 to 10 years than in the group with 11 to 20 years of
      disease. We concluded that the phonoaudiological affection in myotonic dystrophy
      was less intense in patients with later onset of symptoms and less than 10 years
      of disease.

PMID- 8540817
TI  - [Surface electromyography in the diagnosis of lateral dominance in children:
      psychomotor features].
AB  - Surface electromyography was used to verify the lateral dominance in 100 six to
      fourteen years old normal children. Electromyographic records were obtained
      during verbal stimulation. Dexterity was found in 90, sinistrallity in 3 and
      indefinite dominance in 7 patients. Comparing with results from clinical
      examination, the electromyography seems more accurate and easy to perform. The
      responses obtained after verbal stimulations were attributed to a psychomotor
      phenomenon. Mechanisms involved in the production of muscle contractions after
      verbal stimulation, were not proved. Pharmacologic action of cathecolamines on
      the central motor neural subsystems is advanced.

PMID- 8540818
TI  - [Surface electromyography during experimental stress as a tool in the diagnosis
      of tension headache: results in 100 cases].
AB  - We report the use of surface scalp and neck electromyography during experimental
      stress state in a series of 100 out-patients suffering from chronic tension
      headache. Results revealed a 24% to 32% of diagnostic errors in the diagnostic
      obtained by routine anamnestic procedures and following the criteria recommended
      by the Headache Classification Committee of the International Headache Society
      (1988). The electromyography with stress is proposed as a new diagnostic
      criterion for tension headache.

PMID- 8540819
TI  - [Possible stages in the pathogenesis of tension headache and indications for
      treatment].
AB  - Five steps in the pathogenic process involved in the tension headache
      pathogenesis are suggested from a 100 patients clinical study. Therapeutic
      efficacy in the treatment of the tension headache is considered to be linked to
      the relation between the therapeutic agent and the stage in which it has focused
      its effect, in the pathogenic process.

PMID- 8540820
TI  - [Ambulatory follow-up of patients with myelomeningocele in a pediatric hospital].
AB  - Myelomeningocele is the most common congenital malformation of the nervous system
      and despite its complexity and involvement of multiple organs is compatible with
      long survival. The peculiar characteristics of this malformation expose
      myelomeningocele patients to acute and chronic care problems with effects in
      quality of survival. In order to evaluate the quality of the follow-up of spina
      bifida patients in a pediatric hospital, the authors examined 54 patients
      attending the neurosurgical outpatient unity of a pediatric hospital. The lack of
      a multidisciplinary spina bifida clinic in Rio de Janeiro forced the patients to
      pursuit for complimentary medical and paramedical care outside the hospital with
      significant effects in the quality of survival. In consequence, only 25% of the
      patients were able to walk and community ambulation was nearly absent. Only 66.6%
      had a regular rehabilitation program and nearly 50% had routine orthopedics
      consultations. Almost half of the patients had no urological referral at all and
      75% were incontinent, with recurrent urinary infections ranging 72.2%. The rates
      of neurosurgical complications were similar to those observed in the literature.
      We concluded that the quality of survival of patients with neural tube defects is
      strongly influenced by the adverse socio-economical conditions and the lack of a
      spina bifida multidisciplinary clinic.

PMID- 8540821
TI  - [Cognitive heterogeneity in Alzheimer's disease].
AB  - The authors describe and discuss neuropsychological aspects related to the
      functional organization of the brain connected to cognition in 81 Alzheimer's
      disease patients in the Laboratoire Theophile-Alajouanine du Centre de Recherche
      du Centre hospitalier Cote-des-Neiges in the University of Montreal. They
      confront the clinical of homogeneity against the heterogeneity within functional
      organization of the brain. The criteria used for diagnosis were those of the
      NINCDS-ADRDA. All of the patients were in the beginning of the evolution, in
      stages 3 and 4 of Reiberg (Functional Assessment Staging, FAST). The conclusion
      shows that there are two cognitive profiles: a non-recurrent profile, made up by
      the majority of the patients, and the heterogeneity depends on the genetic
      background of each individual; a recurrent profile, made up by a small group of
      patients that show changes in the heterogeneity of clinical, nosological,
      pathological and normal aging forms.

PMID- 8540822
TI  - [Lafora's disease: a possible diagnosis of juvenile dementia].
AB  - Five patients aged 12 to 16 years old were admitted between 1987 and 1994 at the
      neurological unit because of uncontrolled epilepsy. They had had a normal
      development until the adolescence, when a history of poor school performance and
      memory difficulty started. It is emphasized the clinical sequence of dementia
      followed by tonic-clonic seizures and myoclonus, the positive family history and
      the difficult therapeutic management, in spite of multiple anticonvulsant
      combinations, including sodium valproate and clonazepam. The clinical and
      laboratory differential diagnosis were discussed to show that similar cases
      should be submitted to skin biopsy looking for Lafora bodies in apocrine and
      eccrine glands. However, the liver is considered as the most reliable site for
      the biopsy, which in our study showed positivity in four out of the five cases.

PMID- 8540823
TI  - [Neurocysticercosis in the State of Rio Grande do Norte: report of 8 cases].
AB  - The authors present the study of eight patients with cysticercosis of the central
      nervous system observed in the State of Rio Grande do Norte, Brazil. They comment
      about the frequency of the disease. Seizures were present in six patients and
      headache in four. The neurologic examination was abnormal in five patients. The
      diagnosis was based on computed tomography findings in seven patients, and on
      cerebrospinal fluid findings in three.

PMID- 8540824
TI  - [Kennedy disease: report of 2 cases].
AB  - We report two cases of Kennedy's disease (muscle weakness, amyotrophy,
      intentional tremor, endocrine abnormalities, and denervation signs at
      electromyography). This entity must be differentiated from other motor neuron
      disorders by the genetic pattern (X-liked recessive), gynecomastia, testicular
      atrophy, oligospermia and good prognosis. A discussion about the clinical pattern
      and evolution is made.

PMID- 8540825
TI  - Pontine tegmentum hematoma: a case report with the "one-and-a-half" syndrome
      without pyramidal tract deficit.
AB  - The author reports the case of a 54-year-old male patient with a pontine hematoma
      and with the one-and-a-half syndrome, cerebellar ataxia and no signs of pyramidal
      tract involvement. The absence of involvement of the pyramidal tract in the case
      reported herein is likely due to variation in the vascular anatomy of the pons.
      The pathophysiologic mechanisms of the one-and-a-half syndrome and of the
      clinical findings recorded are discussed.

PMID- 8540826
TI  - [Giant aneurysm of the posterior cerebral artery (P3 segment): report of a case].
AB  - A rare case of giant aneurysm of the P3 segment of the posterior cerebral artery
      is presented. The aneurysm was accessed through a combined approach proposed by
      Sano and the aneurysm was treated by proximal clipping. The patient had a good
      postoperative recovery without any neurological deficit. The anatomy and the
      operative approaches are discussed and the neurosurgical literature reviewed.

PMID- 8540827
TI  - Bilateral putaminal hemorrhage related to methanol poisoning: a complication of
      hemodialysis? Case report.
AB  - A case of acute methanol intoxication is presented, in which bilateral putaminal
      hemorrhage developed after hemodialysis. Even though the patient was initially
      comatose and profoundly acidotic, favorable outcome was achieved, with long-term
      neurologic impairments essentially restricted to mild crural paraparesis,
      retrograde amnesia, and marked visual deficit. A comparative literature review is
      evaluated.

PMID- 8540828
TI  - [Wernicke's encephalopathy: report of a case with obstructive pyloric syndrome].
AB  - The authors present one case of Wernicke's encephalopathy in a patient with
      obstructive pyloric syndrome caused by gastric adenocarcinoma, without previous
      history of alcoholism or malnutrition. They comment on the importance of
      physiological aspects of thiamine as a co-enzyme of transketolase and pyruvate
      decarboxilase in the metabolic pathway for ATP production and the possibility of
      existing an interaction between genetical and environmental factors in the onset
      the symptoms. They draw attention for the clinical diagnosis, which should be
      precocious for the therapy with thiamine to be effective, especially in patients
      without previous history of alcoholism or malnutrition.

PMID- 8540829
TI  - [Atypical neurosyphilis: report of a case].
AB  - The present study is based on the observation of a case at the inpatient service
      of Clinica Olive Leite in August 1992. A 31 years old female patient, showing
      cognitive deterioration and dementia syndrome associated with paranoid elements
      (hallucination and delirium), was admitted as a case of organic psychosis.
      Diagnostic investigation evidenced positive tests for syphilis in serum and
      cerebrospinal fluid. The following peculiar aspects are emphasized in this case:
      severe clinical presentation, severe presentation symptoms (amaurosis and a
      severe cognitive deficit), sex, age, and for being the first case diagnosed in
      the service since 1968 (occasion in which the last neurosyphilis case was
      registered in its data bank). In the following nine months, after penicillin
      therapy, the patient showed some improvement characterized by a reduction of
      productive symptoms of hallucination and delusion type, reduction of the
      cognitive deficit, and a higher production of the social behavior activities.

PMID- 8540830
TI  - [Actinomycotic abscess of the cerebellum: a case report].
AB  - A 38 year-old man presented fever and a clinical picture of intracranial
      hypertension and ataxic syndrome. A CT-scan disclosed an expanding lesion of the
      cerebellum. Surgical excision of the lesion was performed and pathological
      examination made the diagnosis of an actinomycotic abscess. The probable primary
      source of infection were the lungs and/or oral cavity. The postoperative course
      was uneventful, with complete recovery after a long period of treatment with
      penicillin (IV and PO). The authors review some aspects about central nervous
      system involvement in actinomycosis.

PMID- 8540831
TI  - Fulminant form of multiple sclerosis simulating brain tumor: a case with
      parkinsonian features and pathologic study.
AB  - We describe the case of a 48 year-old man in whom the clinical features, CT and
      MR scans were suggestive of a brain tumor but, posteriorly, another MRI study,
      CSF examination and brain biopsy supported the diagnosis of multiple sclerosis.
      Interestingly, this patient presented parkinsonian features, probably in
      connection with the underlying disease.

PMID- 8540832
TI  - [Temporal lobe epilepsy: report of an intact patient 26 years later without
      treatment].
AB  - We present the case of a 36 years old man with temporal lobe epilepsy since 10
      years old without treatment, and daily complex partial seizures and weekly tonic
      clonic seizures. The diagnosis was made by clinical aspects and
      electroencephalographic findings. CT scan was normal. Cognitive functions were
      tested and showed no alterations. The patient had normal clinic, neurologic and
      mental exam.

PMID- 8540833
TI  - Central and peripheral nervous complications of dental treatment.
AB  - This review outlines the complications involving the central or peripheral
      nervous system arising from dental procedures reported in the last decade. By far
      the commonest complications were related to intraoperative mechanical peripheral
      nerve injury. Trauma to branches of the mandibular nerve occurring during oral
      operations may potentially result in varying degrees of hypoesthesia,
      paresthesia, dysesthesia or in chronic pain syndromes. An increase in malpractice
      suits related to such a complication has been recognized in the late years. A
      warning of the possibility of occurrence of this complication should to be given
      to all patients undergoing risky procedures as part of the process of obtaining
      informed consent to operation. Mandibular third molar extraction seems to be
      alone the most hazardous procedure related to mechanical nerve injuries and also
      with anesthesiological accidents. Severe but rather infrequent infectious
      (meningitis, brain abscess and cavernous sinus thrombophlebitis) and
      anesthesiological complications (occular and facial palsies, optic nerve injury
      and complications related to general anesthesia) were also reported in this
      period.

PMID- 8540834
TI  - [Binswanger's disease: evolution of thought and a proposed diagnostic triad].
AB  - We review the evolution of the concept of Binswanger's disease from his original
      description in 1894 to our days. We emphasize the conceptual impact caused by CAT
      scan. Finally, we propose a diagnostic triad based on clinical, neuropathological
      and radiological trends. We believe Binswanger's disease has a clear identity
      despite the lack of solid diagnostic criteria.

PMID- 8540835
TI  - [Mutism after posterior fossa tumor surgery: report of 2 cases].

PMID- 8540837
TI  - Xth World Congress of the International Society for Artificial Organs in
      conjunction with the International Faculty for Artificial Organs. Taipei,
      November 14-18, 1995. Abstracts.

PMID- 8540836
TI  - [Hemichorea associated with cerebral toxoplasmosis and AIDS].

PMID- 8540838
TI  - Conjunctival malignant melanoma.

PMID- 8540839
TI  - Breast carcinoma metastatic to the optic nerve.

PMID- 8540840
TI  - Magnetic resonance imaging in patients with low-tension glaucoma.

PMID- 8540841
TI  - Sudden visual loss associated with sexual activity.

PMID- 8540842
TI  - Diabetic retinopathy following lipid disease of the capillary endothelium.

PMID- 8540843
TI  - Metastatic ocular and cutaneous melanoma: a comparison of patient characteristics
      and prognosis.

PMID- 8540844
TI  - Malignant eyelid tumors in an Indian population.

PMID- 8540845
TI  - Long-term results after penetrating keratoplasty for Fuchs' endothelial
      dystrophy.
AB  - OBJECTIVE: To determine the graft survival, visual outcome, complications, and
      frequency of subsequent cataract extraction after penetrating keratoplasty for
      Fuchs' dystrophy. DESIGN: The medical records of 236 patients with the diagnosis
      of Fuchs' dystrophy who were examined on the Cornea Service at Wills Eye
      Hospital, Philadelphia, Pa, between January 1, 1988, were reviewed
      retrospectively. SUBJECTS: Penetrating keratoplasties had been or were
      subsequently performed on 130 phakic eyes of the 236 patients with Fuchs'
      dystrophy. Results were analyzed in 126 eyes with at least 1 year of follow-up.
      Statistical analysis was done to determine the risk factors for subsequent
      cataract surgery in the first eye of patients who had penetrating keratoplasty as
      their initial surgical procedure. RESULTS: Mean +/- SD follow-up after
      transplantation was 8.4 +/- 4.8 years. The graft remained clear in 112 eyes
      (89%). A best corrected acuity of 20/40 or better was achieved in 81 eyes (64%).
      Graft rejection occurred in 37 eyes (29%). Subsequent cataract surgery was
      performed in 55 eyes (44%), and the mean time from transplantation was 3.5 +/-
      3.4 years. Advanced age at the time of transplantation was a significant risk
      factor for having cataract extraction (P = .003, Mantel-Haenszel chi 2 test) and
      a shorter time to cataract surgery after penetrating keratoplasty (P = .04,
      Mantel-Haenszel chi 2 test). Pregraft lens status approached significance as a
      risk factor for subsequent cataract surgery (P = .07, Mantel-Haenszel chi 2
      test). CONCLUSIONS: Long-term results are favorable after penetrating
      keratoplasty for Fuchs' dystrophy. In older patients with Fuchs' dystrophy and
      mild-to-moderate lens changes, combines penetrating keratoplasty, cataract
      extraction, and intraocular lens implantation procedure should be considered.

PMID- 8540846
TI  - The effect of perimetric experience in patients with glaucoma.
AB  - OBJECTIVE: To study prospectively the effects of perimetric learning in glaucoma
      patients. PATIENTS AND METHODS: Twenty-five patients with newly detected glaucoma
      underwent repeated perimetric testing using the 30-2 full threshold program with
      the Humphrey perimeter. Each patient was tested five times at about 1-week
      intervals. No patient had undergone perimetry before entering the study. RESULTS:
      In most patients, visual field results improved with repeated testing.
      Improvements were obvious in 21 of the 37 glaucomatous eyes. Means of mean
      deviation values improved significantly, by 2.81 dB (P < .001, analysis of
      variance), between the first and the second test session, and no significant
      differences were shown between tests 2 and 5. Fields with moderate field loss
      improved more than fields with milder or more severe loss. Learning effects were
      more pronounced peripherally than centrally, and better points improved more than
      more disturbed ones. CONCLUSIONS: The effects of perimetric learning were large
      and common, and are clinically important. Baselines for perimetric follow-up of
      patients with glaucoma should consist of more than one test. To avoid misleading
      conclusions, studies using perimetry to assess the effects of glaucoma treatment
      should take learning effects into consideration.

PMID- 8540847
TI  - Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of
      relapsed cytomegalovirus retinitis in patients with AIDS. The Cytomegalovirus
      Retreatment Trial. The Studies of Ocular Complications of AIDS Research Group in
      Collaboration with the AIDS Clinical Trials Group.
AB  - OBJECTIVES: To determine the best therapeutic regimen, using currently approved
      drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis. DESIGN:
      Multicenter, randomized, controlled clinical trial. SETTING: Ophthalmology, and
      acquired immunodeficiency syndrome (AIDS) services at tertiary care medical
      centers. PATIENTS: Two hundred seventy-nine patients with AIDS and either
      persistently active or relapsed CMV retinitis. INTERVENTION: Patients were
      randomized to one of three therapeutic regimens: induction with foscarnet sodium
      at 90 mg/kg intravenously every 12 hours for 2 weeks, followed by maintenance at
      a dosage of 120 mg/kg per day (foscarnet group); induction with ganciclovir
      sodium at 5 mg/kg intravenously every 12 hours for 2 weeks followed by
      maintenance at 10 mg/kg per day (ganciclovir group); or continuation of previous
      maintenance therapy plus induction with the other drug (either ganciclovir or
      foscarnet) for 2 weeks followed by maintenance therapy with both drugs,
      ganciclovir sodium at 5 mg/kg per day and foscarnet sodium at 90 mg/kg per day
      (combination therapy group). OUTCOMES: Mortality, retinitis progression, visual
      acuity, visual fields, and morbidity. RESULTS: The mortality rate was similar
      among the three groups. Median survival times were as follows: foscarnet group,
      8.4 months; ganciclovir group, 9.0 months; and combination therapy group, 8.6
      months (P=.89). Comparison of retinitis progression, as evaluated in a masked
      fashion by the centralized Fundus Photograph Reading Center (FPRC), revealed that
      combination therapy was the most effective regimen for controlling the retinitis.
      The median times to retinitis progression were as follows: foscarnet group, 1.3
      months; ganciclovir group, 2.0 months; and combination therapy group, 4.3 months
      (P<.001). Although no difference could be detected in visual acuity outcomes,
      visual field loss and retinal area involvement on fundus photographs both
      paralleled the progression results, with the most favorable results in the
      combination therapy group. The rates of visual field loss were as follows:
      foscarnet group, 28 degrees per month; ganciclovir group, 18 degrees per month;
      combination therapy group, 16 degrees per month (P=.009); and the rates of
      increase of retinal area involved by CMV were as follows: foscarnet group, 2.47%
      per month; ganciclovir group, 1.40% per month; and combination therapy group,
      1.19% per month (P=.04). While side effects were similar among the three
      treatment groups, combination therapy was associated with the greatest negative
      impact of treatment on quality-of-life measures. CONCLUSION: For patients with
      AIDS and CMV retinitis whose retinitis has relapsed and who can tolerate both
      drugs, combination therapy appears to be the most effective therapy for
      controlling CMV retinitis.

PMID- 8540848
TI  - Retinal venous sheathing and the blood-retinal barrier in multiple sclerosis.
AB  - OBJECTIVE: To assess the temporal relations among retinal appearance, disruption
      of the blood-retinal barrier, clinical subgroup, disease course, and disruption
      of the blood-brain barrier in multiple sclerosis. DESIGN: A 6-month prospective
      study involving monthly clinical ocular examinations, color fundus photography,
      fundus fluorescein angiograms, and magnetic resonance brain scans with gadolinium
      diethylenetriamine-pentaacetic acid (Gd-DPTA) enhancement. SETTING: University
      based ophthalmology and neurology departments. PATIENTS: Twenty-three patients
      with relapsing-remitting, primary-progressive, or secondary-progressive multiple
      sclerosis. RESULTS: Retinal venous sheathing was seen in six patients. The
      appearances observed included focal venous sheathing, diffuse venous sheathing,
      sheathing centered on sites of arteriovenous crossover, and focal perivenous
      hemorrhage. Arteriolar sheathing was also observed in one patient. Venous leakage
      on fundus fluorescein angiogram was detected in three patients, all of whom also
      had sheathing. The following three patterns of disruption of the blood-retinal
      barrier were seen on fundus fluorescein angiogram: focal leakage, extensive
      leakage, and very late wall staining. In one patient, the leakage was transitory.
      No correlations were observed between ophthalmologic features and multiple
      sclerosis clinical subgroup, disease course, or the number of new (Gd-DTPA
      enhancing) lesions on magnetic resonance imaging. CONCLUSIONS: Disruption of the
      blood-retinal barrier, like the more frequent disruption of the blood-brain
      barrier seen on magnetic resonance imaging, is often unrelated to clinical
      neurologic relapses and occurs with apparently similar frequency in different
      patients independent of clinical disease course.

PMID- 8540850
TI  - Persistent palinopsia following ingestion of lysergic acid diethylamide (LSD).
AB  - OBJECTIVE: To identify a distinctive chronic visual complication of lysergic acid
      diethylamide (LSD) use. DESIGN: Description of the clinical findings in three
      patients with this disorder. SETTING: A neuro-ophthalmology referral center.
      RESULTS: All three patients experienced prolonged afterimages (palinopsia) during
      LSD intoxication and have continued to be symptomatic up to 3 years after they
      ceased to ingest the drug. Results of neuro-ophthalmologic and neurologic
      examinations and neuroimaging and electrophysiologic studies were normal.
      CONCLUSIONS: We have described three patients in whom persistent palinopsia
      developed following ingestion of LSD. Clinicians should inquire about past LSD
      use in all patients who initially have seemingly spontaneous, isolated
      palinopsia. Recognition of this distinctive clinical syndrome associated with LSD
      use might avoid unnecessary anxiety and excessive diagnostic tests for patients
      with this disorder.

PMID- 8540849
TI  - Visual perception elicited by electrical stimulation of retina in blind humans.
AB  - OBJECTIVE: To evaluate the feasibility of bypassing damaged photoreceptors and
      electrically stimulating the remaining viable retinal layers to provide limited
      visual input to patients who are blind because of severe photoreceptor
      degeneration. METHODS: In the operating room with the patient under local
      anesthesia, focal electrical stimulation of the retinal surface with brief
      biphasic pulses was performed using small probes inserted through the sclera. The
      procedure was performed in five subjects who had little or no light perception.
      Three subjects had retinitis pigmentosa, one had age-related macular
      degeneration, and one had unspecified retinal degeneration from birth. RESULTS:
      Stimulation elicited visual perception of a spot of light (phosphene). Subjects
      who previously had useful vision accurately localized the phosphenes according to
      the retinal area stimulated. Two subjects could track the movement of the
      stimulating electrode by reporting movement of the elicited phosphene, and could
      perceive two simultaneous phosphenes on independent stimulation with two
      electrodes. In a resolution test, one of the subjects with no light perception in
      his left eye resolved phosphenes at 1.75 degrees center-to-center distance (ie,
      4/200 OS visual acuity). CONCLUSIONS: Local electrical stimulation of the retinal
      surface in patients blind from outer retinal disease results in focal light
      perception that seems to arise from the stimulated area. Such findings in an
      acute experiment warrant further research into the possibility of prolonged
      retinal stimulation, improved resolution, and ultimately, an intraocular visual
      prosthesis.

PMID- 8540851
TI  - Human excimer laser keratectomy. Immunohistochemical analysis of healing.
AB  - OBJECTIVE: To analyze human corneal responses to excimer laser by
      immunohistochemistry. METHODS: Corneas cultured for 3 weeks after laser ablation
      or taken from patients 5 to 16 months after laser treatment were exposed to
      antibodies to beta, integrin; types VII, IV, and III collagen; fibronectin; type
      I procollagen; and prolyl 4-hydroxylase. Antibody distributions were compared
      with those of normal corneas and unablated regions of treated corneas. RESULTS:
      After 3 weeks, distribution of beta, integrin, and types VII and IV collagen was
      patchy; heavy deposits of fibronectin appeared subepithelially. Keratocytes
      stained for prolyl-4-hydroxylase and type I procollagen. With increasing
      postoperative time, fibronectin diminished, and beta 4 integrin and type VII
      collagen became linear, stromal staining of types III and IV collagen increased
      and their diminished. CONCLUSIONS: Components of basement membrane, attachment
      complexes, and stromal matrix are synthesized shortly after laser treatment.
      Changes in these elements persist for 16 months in the human cornea.

PMID- 8540852
TI  - Comparative intravitreal antibiotic therapy for experimental Enterococcus
      faecalis endophthalmitis.
AB  - OBJECTIVE: To evaluate the most effective intravitreal antibiotic treatment of
      vancomycin-sensitive and -resistant Enterococcus faecalis endophthalmitis.
      DESIGN: Animal experiment. SETTING: Seventy-eight New Zealand white rabbits
      received an intravitreal injection of 10(5) vancomycin-sensitive or -resistant E
      faecalis organisms in one eye. Infections were allowed to proceed 3 hours before
      dividing animals randomly into the following treatment groups (n = 6, each): the
      vancomycin-sensitive E faecalis model--(1) vancomycin (1 mg/0.1 mL), (2) combined
      vancomycin (1 mg/0.1 mL) and amikacin (0.4 mg/0.1 mL), (3) combined vancomycin (1
      mg/0.1 mL) and gentamicin (0.1 mg/0.1 mL), (4) combined vancomycin (1 mg/0.1 mL)
      and ceftazidime (2 mg/0.1 mL), (5) combined ampicillin (5 mg/0.1 mL) and
      gentamicin (0.1 mg/0.1 mL), and (6) pristinamycin (1 mg/0.1 mL); and the
      vancomycin-resistant E faecalis model--(1)same as above, excluding group 4.
      Control groups received sterile balanced salt solution. Twenty-four hours
      following intravitreal treatment, vitreous humor was collected for quantitative
      bacteriological studies. RESULTS: Intravitreal therapy with combined vancomycin
      and amikacin provided the most effective reduction of vancomycin-sensitive E
      faecalis organisms compared with combined vancomycin and gentamicin therapy (P
      =.10, Wilcoxon's rank sum test) or any other treatment group (P < .01, Wilcoxon's
      rank sum test). For vancomycin-resistant E faecalis endophthalmitis model, the
      combined ampicillin and gentamicin therapy was the most effective, followed by
      the combined vancomycin and amikacin therapy (P < .01, Wilcoxon's rank sum test).
      CONCLUSIONS: Treatment with intravitreal vancomycin plus amikacin and with
      intravitreal ampicillin plus gentamicin provide an effective bactericidal therapy
      for severe experimental vancomycin-sensitive and -resistant E faecalis
      endophthalmitis, respectively.

PMID- 8540853
TI  - Inhibition of vascular endothelial growth factor prevents retinal ischemia
      associated iris neovascularization in a nonhuman primate.
AB  - OBJECTIVE: To determine if the angiogenic peptide vascular endothelial growth
      factor (VEGF) is required for retinal ischemia-associated iris neovascularization
      in a nonhuman primate. METHODS: Laser retinal vein occlusion was used to produce
      retinal ischemia in 16 eyes of eight animals (Macaca fascicularis). Eyes were
      randomized to treatment every other day with intravitreal injections of either a
      neutralizing anti-VEGF monoclonal antibody or a control monoclonal antibody of
      the same isotype. Serial iris fluorescein angiograms were assessed using a
      standardized grading system and masked readers. Retinal VEGF and placental growth
      factor expression were assessed by Northern blotting. The specificity of the
      antibodies was determined in capillary endothelial cell proliferation assays
      prior to intravitreal injection. RESULTS: Zero of eight eyes receiving the
      neutralizing anti-VEGF antibodies developed iris neovascularization. Five of
      eight control antibody-treated eyes developed iris neovascularization. The
      difference was statistically significant (P = .03). Intravitreal antibody
      injection did not impair the ability of the ischemic retina to increase VEGF
      messenger RNA expression. The anti-VEGF antibodies specifically inhibited VEGF
      driven capillary endothelial cell proliferation in vitro. CONCLUSION: These data
      demonstrate that VEGF is required for iris neovascularization in an adult
      nonhuman primate eye. The inhibition of VEGF is a new potential therapeutic
      strategy for the treatment of ocular neovascularization.

PMID- 8540855
TI  - Mechanisms of photoreceptor death in retinal degenerations. From the cell biology
      of the 1990s to the ophthalmology of the 21st century?
AB  - There is still no effective treatment for retinal degenerative diseases such as
      retinitis pigmentosa (RP), in which the loss of photoreceptor cells causes visual
      loss and eventually blindness. In addition to its intrinsic scientific interest,
      basic research aimed at elucidating the biological mechanisms regulating the
      survival and function of cones and rods is also important from a clinical
      perspective, since it could provide a foundation for the development of
      therapeutic strategies for these diseases. The recent observation that
      photoreceptor degeneration in several RP animal models occurs through programmed
      cell death (apoptosis) illustrates this possibility well. This article will
      present a brief overview of recent research contributions toward the search for
      treatments for retinal degenerations of genetic origin.

PMID- 8540854
TI  - Autosomal dominant cone-rod dystrophy associated with mutations in codon 244
      (Asn244His) and codon 184 (Tyr184Ser) of the peripherin/RDS gene.
AB  - OBJECTIVE: To characterize clinical findings associated with mutations in codon
      244 (Asn244His) and codon 184 (Tyr184Ser) of the peripherin/RDS gene. DESIGN:
      Case reports with clinical features and results of fluorescein angiography,
      electroretinography, kinetic visual field testing, and DNA analysis. SETTING:
      University medical center. PATIENTS: Four affected members of two Japanese
      families with autosomal dominant cone-rod dystrophy associated with transversion
      mutations in codon 244 (Asn244His) and codon (Tyr184Ser) of the peripherin/RDS
      gene. RESULTS: Characteristic features included the initial symptoms of decreased
      visual acuity, macular degeneration, central or paracentral scotoma, cone
      mediated electroretinographic responses that were more impaired than rod-mediated
      responses, and pigmentary degeneration in the midperipheral retina in the late
      stage. These phenotypic features corresponded to cone-rod dystrophy type 2a by
      the classification of Szlyk and associates. CONCLUSIONS: The Asn244His and
      Tyr184Ser mutations in the peripherin/RDS gene cause con-rod dystrophy type 2a.
      These findings imply that a mutation in codon 244 or codon 184 of the
      peripherin/RDS gene affects the functions and/or structural stability of cones
      and rods.

PMID- 8540856
TI  - Empirical or culture-guided therapy for microbial keratitis? A plea for data.
AB  - In the United States, about 30,000 bacterial corneal ulcers are treated annually.
      Compared with 100, or even 20, years ago ophthalmologists today have available to
      them many diagnostic tools (including special media and bacterial identification
      techniques), and in impressive assortment of antibiotics. Many reviews and book
      chapters describe the uses of microbiologic studies--from Gram and Giemsa
      staining to media inoculation to immunofluorescence and even molecular genetics-
      to identify causative organisms. This literature also describes the formulas for
      preparation of highly concentrated, "fortified" antibiotics for initial treatment
      of bacterial keratitis, until culture and sensitivity results are available to
      guide modifications in therapy. It would seem, therefore, that "experts" in the
      field of corneal and external diseases have reached consensus on an appropriate
      initial microbiologic evaluation and treatment of suspected microbial keratitis,
      and the large body of literature on this topic might be considered to represent
      practice guidelines. It comes as a surprise to many that these published
      "guidelines" apparently are routinely ignored in current clinical practice.

PMID- 8540857
TI  - Herpetic eye disease study. You can help.

PMID- 8540858
TI  - Structure and function of the corneal endothelium in diabetes mellitus type I and
      type II.
AB  - OBJECTIVE: To measure and compare corneal endothelial morphologic characteristics
      and function in subjects with diabetes mellitus types I and II. DESIGN: Forty
      nine patients with diabetes mellitus type I and 60 patients with diabetes
      mellitus type II were recruited from the active practice of the Mayo Clinic,
      Rochester, Minn. Thirty-one normal subjects, divided by age into two overlapping
      groups of 20 each, served as controls. Corneal endothelial permeability and
      corneal autofluorescence were measured by fluorophotometry. Central corneal
      endothelial photographs were taken with a wide-field specular microscope, which
      also measured the corneal thickness. RESULTS: Neither the type I nor the type II
      diabetics differed from their controls in endothelial permeability and
      endothelial cell density. The type I diabetics had polymegethism, pleomorphism,
      increased corneal thickness, and increased corneal autofluorescence compared with
      their controls. Similar measured values were found in the type II diabetics, but
      they did not differ significantly from those of their age-matched controls. The
      type II diabetics were older than the type I diabetics, and the older control
      group showed changes similar to those seen in the diabetics; these changes were
      presumably associated with aging. The severity of retinopathy was significantly
      correlated only with corneal autofluorescence. CONCLUSION: The corneas of
      patients with type I diabetes mellitus exhibit abnormalities in endothelial cell
      morphologic characteristics and corneal autofluorescence. The changes resemble
      those that occur with aging in normal subjects, making them difficult to discern
      as abnormal in type II diabetics, who are usually older. We found no
      abnormalities in endothelial permeability in either type I or type II diabetics.

PMID- 8540859
TI  - Emerging antibiotic resistance: real and relative.

PMID- 8540860
TI  - Angiosarcoma metastatic to the orbit.
AB  - Angiosarcoma is a rare malignant endothelial cell tumor. Few reports of primary
      orbital angiosarcoma exist in the literature. A 46-year-old woman had a 3-month
      history of progressive diplopia and right-sided exophthalmos. Magnetic resonance
      imaging showed a right intraconal mass, consistent with a cavernous hemangioma.
      Ultrasound examination showed a isolated mass with moderate vascularity,
      consistent with a metastatic lesion. Subtotal excision through a lateral
      orbitotomy was performed. Tissue was stained with hematoxylineosin, periodic acid
      Schiff, and immunohistochemical stains for factor-VIII-related antigen and Ulex
      europaeus agglutinin I lectin. Lateral orbitotomy biopsy specimens showed an
      angiosarcoma, similar to a primary breast angiosarcoma that had been resected 2
      years previously. The patient initially underwent orbital exenteration for her
      only known metastasis. Despite a multidisciplinary and aggressive approach to
      this tumor, the tumor recurred, and the patient died.

PMID- 8540861
TI  - Anaphylactic shock following indocyanine green angiography.

PMID- 8540862
TI  - Anaerobic and aerobic isolates from a subperiosteal orbital abscess in a 4-year
      old.

PMID- 8540863
TI  - A new instrument (forceps/scissors) for preretinal membrane peeling,
      segmentation.
AB  - This new intraocular instrument has been developed to aid vitreoretinal surgeons
      in the removal of preretinal membranes. It functions as both a forceps for
      membrane peeling and scissors for cutting.

PMID- 8540864
TI  - BCG in bladder cancer--a warning.

PMID- 8540865
TI  - Post cardiac surgery acute renal failure in the 1990s.

PMID- 8540866
TI  - Human gene therapy.

PMID- 8540867
TI  - Acute renal failure following cardiac surgery: incidence, outcomes and risk
      factors.
AB  - BACKGROUND: Acute renal failure (ARF) is a recognised complication following
      cardiac surgery, but the incidence varies widely in the published literature and
      there are no Australian data available to help predict the risks of ARF in
      patients with pre-existing renal disease. AIM: To determine the incidence,
      outcome and risk factors for ARF following cardiac surgery. METHODS: A
      retrospective case control analysis of 903 consecutive patients who had cardiac
      surgery (795 CABG, 68 valve/septal surgery, 40 combined valve/CABG) in 1992-93.
      ARF was defined as doubling of serum creatinine concentration (Cr) to > 0.13
      mmol/L if serum Cr was < or = 0.13 mmol/L pre-operatively, or else a rise in
      serum Cr of > or = 0.10 mmol/L after cardiac surgery. For each subject with ARF,
      two case control subjects were matched for date of surgery, surgeon, age, sex,
      type of surgery and pre-operative serum Cr to permit analysis of the influence of
      pre-operative factors (hypertension, diabetes mellitus, left ventricular systolic
      dysfunction) and for the comparison of cardiopulmonary bypass time upon the
      development of ARF. Subsidiary endpoints were mortality, need for dialysis and
      length of hospital stay. RESULTS: ARF developed in only 1.1% of patients with
      'normal' pre-operative renal function (creatinine < or = 0.13 mmol/L) and none
      required dialysis. ARF developed in 16% of those with impaired pre-operative
      renal function, 20% of whom required dialysis. Mortality from ARF was 13%. The
      risk of ARF rose from 10.4% in those with pre-operative serum Cr 0.14-0.20 mmol/L
      to 36.8% if the serum Cr was > 0.20 mmol/L (p < 0.01). Mortality was higher (4.2%
      vs 0.7%, p < 0.01) and length of hospital stay longer (14.5 vs nine days
      [median], p < 0.001) in those with impaired pre-operative renal function. ARF was
      more likely in those over 65 years, if valve surgery was included and where there
      was prolonged cardiopulmonary bypass time. CONCLUSIONS: These data confirm that
      ARF following cardiac surgery is uncommon without pre-operative impairment of
      renal function but currently carries a mortality rate of 13%. Impaired renal
      function alone is associated with higher mortality and prolonged hospital stay.
      Studies to prevent ARF in this setting should focus on the high risk subsets
      described in this study.

PMID- 8540868
TI  - Regional differences in cardiovascular risk factor prevalence in Tasmania: are
      they consistent with the increased cardiovascular mortality?
AB  - BACKGROUND: The death rate from cardiovascular disease in Tasmania has been among
      the highest in Australian States for a number of years. The North-West (NW) and
      Northern regions of Tasmania account for most of the increased mortality. AIMS:
      To determine the prevalence of cardiovascular risk factors in the North and NW
      regions of Tasmania and to ascertain whether any differences are consistent with
      the regional patterns of mortality for ischaemic heart disease (IHD) within the
      State. METHODS: The design of the study was almost identical to the previous
      National Heart Foundation (NHF) Risk Factor Prevalence Survey conducted in 1989.
      The subjects, aged 20-69 years, were randomly selected from the Electoral Roll
      with 1146 subjects participating in the North and 1219 in the NW. Subjects
      answered a detailed questionnaire and then underwent a brief physical examination
      with venipuncture for blood lipids. Hobart data from the NHF Risk Factor
      Prevalence Survey in 1989 were used as an estimate of risk factor prevalence in
      the Southern region. RESULTS: In both males and females, mean systolic blood
      pressure was significantly higher in the NW than the South which was in turn
      higher than the North. Mean serum cholesterol levels in males were higher in the
      NW than the North. Smoking behaviour was similar in males and females in all
      regions. Males and females in the NW and North were more inactive than those in
      the South. Similar proportions in all regions were on either 'no specific' or
      'fat modified' diets. Body mass index in males and females was higher in the NW
      and North but waist to hip ratios failed to show a consistent trend. CONCLUSIONS:
      While the NW has an unfavourable risk factor profile compared with the South, the
      North does not. The risk factor data are broadly consistent with, but unlikely to
      be sufficient to explain fully, the regional differences in mortality from IHD.

PMID- 8540869
TI  - Upper gastrointestinal haemorrhage following coronary artery bypass grafting.
AB  - BACKGROUND: Upper gastrointestinal (UGI) bleeding is a relatively common and
      potentially fatal complication of coronary artery bypass graft (CABG) surgery.
      However, little is known of this problem, including its incidence, predisposing
      factors and safety of endoscopy in these patients. AIM: To document the
      incidence, site, predisposing factors and outcome of UGI bleeding following CABG
      surgery. Also, to assess the safety of UGI endoscopy in these patients. METHOD:
      Retrospective study of UGI haemorrhage following CABG at one institution between
      1976 and 1991. RESULTS: Fifty-five of 10,573 patients (0.5%) suffered a major UGI
      haemorrhage (as defined by need for transfusion or presence of melaena or
      haematemesis associated with hypotension). Of 51 patients undergoing endoscopy or
      laparotomy, 42 (82%) bled from duodenal ulceration. Five patients bled from
      gastric ulcers and one each from oesophagitis and Mallory Weiss tear. Nine
      patients underwent endoscopic therapy, which initially arrested haemorrhage in
      eight patients. However, three patients rebled and required surgery. Eight
      patients underwent surgery as initial therapy, resulting in an overall surgical
      rate of 20%. One patient died due to multi system failure following surgery.
      There were no complications from endoscopy. Patients who bled were more likely to
      have received inotropic support post-operatively prior to the haemorrhage (p <
      0.05) and tended to be older than controls (mean age 65.6 years vs 58.7 years, p
      < 0.01). Twenty-one of the patients (38%) who bled had a past history of peptic
      ulceration or dyspepsia compared with 9% of controls (p < 0.001). Seven (12.5%)
      had previously bled from peptic ulceration. Patients who bled were less likely to
      have received H2-receptor antagonists in the perioperative period than controls
      (4% vs 20%, p < 0.05). CONCLUSION: Upper GI haemorrhage following CABG is
      relatively frequent. It is usually secondary to duodenal ulceration. Endoscopy is
      a safe procedure in this patient group. Mortality did not differ between index
      patients who suffered a UGI haemorrhage and controls undergoing CABG who did not
      bleed.

PMID- 8540870
TI  - Initial validation of a bowel symptom questionnaire and measurement of chronic
      gastrointestinal symptoms in Australians.
AB  - BACKGROUND: Chronic gastrointestinal (GI) symptoms are believed to be common in
      the general population, but Australian data are lacking. A valid instrument is
      required to assess GI symptoms adequately and determine their prevalence in the
      community. AIMS: To test the feasibility, reliability and concurrent validity of
      a self-report Bowel Symptom Questionnaire (BSQ) as a measure of GI symptoms, and
      obtain preliminary data on the prevalence of symptoms in an Australian population
      based sample. METHODS: Outpatients (n = 63), volunteers (n = 163) and a random
      sample (n = 99) of the Penrith population, Sydney, completed the BSQ. Feasibility
      was evaluated in 264 subjects. Reliability was measured by a test-retest
      procedure (n = 43), while concurrent validity was documented by comparing self
      report data with an independent interview (n = 20). The response rate in the
      population mail survey was 68%. Prevalence data on bowel symptoms in the
      community sample (n = 99) were age and gender standardised to the Australian
      population. RESULTS: The majority of subjects found the BSQ easy to complete
      (97%) and understand (97%); 90% completed the questionnaire in half an hour or
      less. Reliability (median kappa 0.70, interquartile range 0.20) and concurrent
      validity (median kappa 0.79, interquartile range 0.26) of GI symptoms were both
      very acceptable. The internal consistency of all GI symptom scales was good
      (Cronbach's Alpha range 0.51-0.74). The prevalence of the irritable bowel
      syndrome (defined as abdominal pain and disturbed defaecation based on two or
      more of the Manning criteria) was 17.2% (95% CI: 10-25%). CONCLUSIONS: The BSQ
      was well accepted and easy to understand; it provided reliable and valid data on
      GI symptoms and should prove useful in large scale epidemiological studies in
      Australia.

PMID- 8540872
TI  - The accuracy of hospital records and death certificates for acute myocardial
      infarction.
AB  - BACKGROUND: In Australia information on the incidence of acute myocardial
      infarction (AMI) is available from routinely collected morbidity and mortality
      data. Given that these data are used for monitoring AMI it is important to assess
      their quality. AIMS: This paper examines the accuracy of the hospital records and
      death certificates. METHODS: Morbidity and mortality data were compared with the
      Newcastle heart disease register which is part of the WHO MONICA Project for 1986
      1991 and sensitivity and positive predictive values calculated. RESULTS: For non
      fatal AMI the hospital diagnostic coding had sensitivity of 78.9% (95% confidence
      interval [CI] 77.1%-80.7%), and positive predictive value of 65.6% (95% CI 63.7%
      67.4%). Sensitivity was higher for men than for women and decreased with
      increasing age. Sensitivity was higher in those with no history of either AMI or
      other ischaemic heart disease (IHD), higher in current smokers than ex-smokers or
      never smokers, and lower in those with a self-reported history of high blood
      pressure. Sensitivity also varied among hospitals. Positive predictive value
      varied only with hospital. Both sensitivity and positive predictive value were
      high for death certificate data--89.9% (95% CI 88.4%-91.3%) and 96.0% (95% CI
      95.1%-97.0%), respectively. CONCLUSIONS: Although the mortality data appear to be
      quite accurate, the hospital data alone are not accurate enough to be used to
      estimate rates or trends of heart attacks. Additional data are required in order
      to determine numbers of non-fatal AMIs accurately.

PMID- 8540871
TI  - Determinants of severity of left ventricular dysfunction in Australian men and
      women with coronary disease aged 65 years or less.
AB  - BACKGROUND: The degree of left ventricular (LV) impairment is an important
      determinant of long term outcome in patients with coronary artery disease (CAD).
      AIM: We aimed to determine variables predictive of the severity of LV dysfunction
      in men and women aged 65 years or less with CAD, and to quantitate their
      contributions. METHODS: We documented atherogenic variables and extent of LV
      impairment and CAD severity at angiography in 521 consecutively studied men and
      women aged 65 years or less (381 males and 140 females). We assessed severity
      from an LV impairment score (Green Lane) and the ejection fraction. We related
      severity to quantitative and categorical variables which included the severity of
      angina (no angina, stable and unstable angina). RESULTS: The LV impairment score
      correlated closely (negatively) with the ejection fraction (r = -0.783, p =
      0.0001). There were eight variables independently predictive of the severity of
      LV impairment assessed by the LV score. The variables in descending order of
      relative importance in predicting the LV scores were past history of myocardial
      infarction (MI), number of significantly diseased vessels (> 50% luminal
      obstruction), life-time smoking dose, log-triglycerides, total cholesterol to HDL
      C ratio, hypertension, age and Body Mass Index (BMI). They were all positive
      relationships. Together they correctly classified the LV scores of 52.6% of the
      patients. Gender was not an independent contributor to the LV score when other
      variables were controlled. When the contributions to the variance in LV scores of
      past history of MI (15.4%) and number of significantly diseased vessels (2.6%)
      were controlled, life-time smoking dose independently explained 2.1% (p < 0.01)
      of the variance. The LV impairment score was 55% higher in heavy smokers than in
      non-smokers (p = 0.01). When we compared patients with stable and unstable
      angina, LV scores are higher and ejection fraction lower in the unstable angina
      patients consistent with them having a greater degree of LV dysfunction.
      CONCLUSION: We conclude that variables other than a history of MI and CAD
      severity contribute significantly to the variance of the degree in LV impairment
      in CAD patients among which the life-time smoking dose, triglycerides, TC/HDL-C,
      hypertension and increased BMI are all relevant to prevention, and that patients
      with unstable vs stable angina usually have more impaired LV function.

PMID- 8540873
TI  - Drug delivery in asthma: a comparison of spacers with a jet nebuliser.
AB  - BACKGROUND: Although spacer devices are frequently used for aerosol therapy in
      asthma, the commonly used spacers have undergone little controlled evaluation,
      and their relation to nebuliser therapy is unclear. AIMS: The aims of this study
      were to compare three delivery methods (Breath-A-Tech spacer, Volumatic spacer
      and jet nebuliser) for the administration of salbutamol to reverse acute
      histamine induced airway narrowing in asthma (Study 1); and to assess asthma
      control during two weeks use of inhaled therapy via Volumatic or Breath-A-Tech
      spacer (Study 2). METHODS: A randomised double-blind cross-over comparison was
      conducted. In Study 1, 27 adults with stable asthma who were currently using
      pressurised metered dose inhaler therapy attended for three study days. On each
      study day subjects inhaled doubling doses of histamine and were randomised to
      receive: (a) salbutamol 200 micrograms via Breath-A-Tech spacer and placebo 200
      micrograms via Volumatic spacer; (b) placebo two puffs via Breath-A-Tech spacer
      and salbutamol 200 micrograms via Volumatic spacer; or (c) salbutamol 1 mg in 2
      mL saline via jet nebuliser. FEV1 and FEF 25-75% were measured at two minute
      intervals for 20 minutes. In Study 2, subjects were randomised to use regular
      asthma medication by Volumatic or Breath-A-Tech spacers and recorded symptoms and
      peak expiratory flow (PEF) in a daily diary. RESULTS: Lung function improved from
      a baseline FEV1 of 51% predicted to 72% after salbutamol inhalation from each of
      the delivery systems. The spacers and nebulisers produced the same maximum
      improvement in FEV1, however, lung function improved more rapidly when salbutamol
      was delivered by spacer. There was no difference in asthma control comparing
      inhaler use via Breath-A-Tech with Volumatic spacer over two weeks use. Subject
      preference favoured the Breath-A-Tech spacer (72% vs 4%). CONCLUSIONS: The
      Volumatic and Breath-A-Tech spacer devices are effective delivery systems in
      asthma and may offer a more rapid response than jet nebulisation at a lower cost.

PMID- 8540874
TI  - Good long-term outcome following surgical repair of post-infarction ventricular
      septal defect.
AB  - BACKGROUND: A post-infarction ventricular septal defect (VSD) is a serious
      complication of a myocardial infarction with 90% of patients dying by two months,
      in published series. Urgent surgical repair improves the prognosis. AIMS: To
      assess the Green Lane Hospital experience over a ten year period, especially with
      regard to hospital mortality and long-term follow up. METHODS: A retrospective
      case note review of all 35 consecutive patients undergoing post-infarct VSD
      repair from 1981 to 1990. Long-term follow up was obtained in all but one patient
      (97%). RESULTS: Twenty-one male and 14 female patients presented with a mean age
      of 67 years (range 51-75). All were in NYHA class 3 or 4, 14 (40%) were in
      cardiogenic shock. Following urgent surgical repair, 30 day mortality was 31% (11
      patients). A further three patients died at two, 33 and 39 months; one patient
      was lost to follow up. At a mean follow up of 61 months (range 16-111), 15
      patients were in NYHA class 1 or 2, five in NYHA class 3 or 4. For the whole
      group (n = 35) the actuarial survival was 66% at one year, 62% at three years and
      58% at nine years. CONCLUSION: Post-infarct VSD surgery is of major prognostic
      benefit with patients obtaining a good long-term outcome.

PMID- 8540875
TI  - Australasian multicentre phase II study of paclitaxel (Taxol) in relapsed ovarian
      cancer.
AB  - BACKGROUND: Until recently there has been no effective therapy for patients with
      relapsed ovarian carcinoma following standard platinum based chemotherapy.
      Paclitaxel has recently been approved for clinical use in this malignancy. AIMS:
      To evaluate the objective response rate and toxicity of paclitaxel in patients
      with relapsed ovarian cancer. METHODS: Paclitaxel was given on an outpatient
      basis as a three hour infusion every 21 days for a maximum of ten cycles to 72
      patients with advanced ovarian cancer previously treated with at least one
      platinum containing regimen. The starting dose was either 175 mg/m2 (patients
      with one or two prior chemotherapy regimens) or 135 mg/m2 (three previous
      regimens). Premedication was given because of the documented risk of
      hypersensitivity reactions to paclitaxel. RESULTS: The overall response rate was
      22% (95% confidence interval [CI] 13% to 34%) in the 72 patients enrolled in the
      study: four patients had a complete response. Three patients (4%) ceased
      treatment due to hypersensitivity reactions. Other significant (WHO grade 3 or 4)
      toxicities included neutropenia (51%), myalgia (14%), neurological (3%), alopecia
      (93%) and nausea and vomiting (3%). The estimated median survival of all patients
      was 9.8 months (95% CI: 9.1-13.0 months) with 44% alive at one year (standard
      error [SE] 7%). CONCLUSIONS: This study confirms that paclitaxel given as a three
      hour infusion has significant activity and acceptable toxicity in advanced
      ovarian carcinoma previously treated with platinum regimens.

PMID- 8540876
TI  - Antiretroviral therapy of human immunodeficiency virus type-1 (HIV-1) infection.

PMID- 8540877
TI  - Current perspectives in hepatitis C.

PMID- 8540878
TI  - Beta-2 agonists in asthma--the Thoracic Society of Australia and New Zealand.

PMID- 8540879
TI  - A randomised controlled trial of community based counselling among those
      discharged from hospital with ischaemic heart disease.

PMID- 8540880
TI  - Acute interstitial nephritis due to Chlamydia psittaci.

PMID- 8540881
TI  - Clostridium perfringens spontaneous bacterial peritonitis.

PMID- 8540882
TI  - Testicular cancer presenting as gastrointestinal bleeding.

PMID- 8540883
TI  - Disseminated intravascular coagulopathy and thrombocytopenia associated with
      clozapine-induced neuroleptic malignant syndrome.

PMID- 8540884
TI  - A granulomatous meningeal mass as the initial presentation of Wegener's
      granulomatosis.

PMID- 8540885
TI  - Dramatic response of livedoid vasculitis to tissue plasminogen activator (tPA)

PMID- 8540886
TI  - Heart rate Poincare plots in heart failure.

PMID- 8540887
TI  - Mitochondrial myopathy developing on treatment with the HMG CoA reductase
      inhibitors--simvastatin and pravastatin.

PMID- 8540888
TI  - Tamoxifen flare--an unusual case of hypercalcaemia and transient rapidly
      progressive pancytopenia.

PMID- 8540889
TI  - A twin-family study of self-report symptoms of panic-phobia and somatization.
AB  - Self-report symptoms of anxiety are widely used in mental health and social
      science research as an index of current psychiatric state. Previous twin studies
      have suggested that genetic factors account for a significant proportion of the
      variance in these symptoms. To replicate and extend these findings, we examined
      self-report symptoms of panic-phobia and somatization in the "Virginia 30,000"
      twin-family sample. Model fitting applied to 80 unique relationships in the twin
      family pedigree produced the following major results: (i) genetic effects were
      significant for both symptom factors, accounting for between 25 and 49% of the
      total variance, with the exception of symptoms of panic-phobia in females, where
      they accounted for 15-16% of the variance; (ii) familial environmental effects
      were absent for symptoms of somatization, while for symptoms of panic-phobia they
      accounted for a very small proportion of variance in males (< or = 1.2%) and a
      modest proportion in females (6-17%); (iii) spousal correlations were present for
      both factors, ranging from +0.05 to +0.20; (iv) genetic factors which influenced
      symptoms were generally the same in males and females, although their effect was
      greater in males; (v) heritability estimates were lower in the population-based
      than in the volunteer sample; and (vi) when test-retest reliability was included
      in the model, results suggest that genetic factors account for at least half of
      the stable variance for all symptom factors, except panic-phobia in females. Our
      results support the validity of previous twin studies of self-report symptoms of
      anxiety and suggest that genetic factors significantly influence these symptoms
      but familial-environmental factors play little or no etiologic role.

PMID- 8540890
TI  - Family patterns in handedness: evidence for indirect inheritance mediated by
      birth stress.
AB  - The most common alternative to a genetic explanation of left-handedness is that
      sinistrality arises because of birth stress factors. In a sample of 1398
      subjects, the association between birth stress and left-handedness was confirmed.
      More importantly, it was found that left-handed mothers are more likely to have
      birth-stressed offspring and that the presence of any left-handed sibling
      increases the likelihood of a history of birth stress in the proband. This was
      interpreted as suggesting that a plausible alternative to the genetic explanation
      for the usual pattern of association observed in family studies of handedness
      (where a left-handed mother increases the probability of left-handed offspring)
      is that the mother-offspring association may actually be mediated by birth stress
      rather than representing heritable aspects of handedness.

PMID- 8540891
TI  - Parental hand preference and manual functional asymmetry in preschool children.
AB  - Hand preference and hand skill in 1150 normal children between 3 and 6 years of
      age and hand preference of their parents were assessed to study the effect of
      parental hand preference on different dimensions of manual asymmetry in children.
      Children hand skill was measured with a computerized version of the Peg Moving
      Task which allowed us to split the overall performance into two components, a
      "transport time" and a "search time." Paternal and maternal left-handedness was
      significantly related to child left-handedness. Both components of hand skill
      asymmetry were reduced with mother's left-handedness. and one component (search
      time) with father's left-handedness. A significant impact of paternal and
      preference on child hand skill asymmetry, after controlling for child hand
      preference, was observed. When this analysis was limited to strong right-handed
      children, a greater paternal effect on child hand skill emerged. These results
      show the usefulness of performance tasks in detecting parent-child associations
      concerning manual functional asymmetry.

PMID- 8540892
TI  - Childhood hyperactivity scores are highly heritable and show sibling competition
      effects: twin study evidence.
AB  - Hyperactivity has consistently been shown to be familial. Until recently however,
      due to a lack of systematic twin evidence, it has remained uncertain to what
      extent familial transmission can be explained by genetic factors. We used a
      systematically ascertained population-based sample of twin pairs aged between 8
      and 16 years old to explore the role of genetic influences on maternally rated
      hyperactivity scores. Hyperactivity scores were found to be substantially
      heritable. The data were best explained by a model which incorporated sibling
      competitive effects as well as additive genetic factors. These findings suggest
      not only that hyperactivity scores are influenced by genetic factors but that
      sibling interaction effects are also of importance.

PMID- 8540893
TI  - Quantitative trait loci (QTL) for circadian rhythms of locomotor activity in
      mice.
AB  - The locomotor activity of male mice (Mus musculus) was monitored by infrared
      photo-electric beams under three lighting regimens: LD (12 h of light and 12 h of
      dark), DD (constant dark), and LL (constant broad-spectrum light, 10 lux).
      Circadian period of locomotor activity (tau) was compared among 3 inbred strains
      of mice, C57BL/6J (B6), BALB/c (C), and DBA/2J (D2), and 26 recombinant inbred
      strains B x D (B6 x D2). The tau under both continuous low-intensity light and
      continuous darkness varied significantly among strains. Under DD the mean tau was
      23.8 h for B6, 23.7 h for D2, and 23.6 h for C. Under LL the mean tau was 25.1 h
      for B6, 23.9 h for D2, and 25.5 h for C. Frequency histograms of the mean tau of
      26 B x D RI mouse strains (three to seven animals per strain) in either DD or LL
      and the difference between them, delta tau, had distributions which appeared
      unimodal, suggesting polygenic inheritances. The narrow-sense heritability
      determined using 26 strains of B x D RI mice was about 55% for tau and about 38%
      for both tau in LL and delta tau. An estimated four loci contribute to the
      variance of tau in constant darkness and five to the variance of tau in constant
      low-intensity light among the strains studied. Quantitative trait locus (QTL)
      analysis identified several potential genetic loci associated with tau in
      constant darkness, tau in constant low-intensity light, and delta tau. The
      associations of highest probability for each of these traits were the D1Nds4
      locus (p < .001) on mouse chromosome 1, the D5Ncvs52 locus (p < .05) on mouse
      chromosome 5, and the Pmv12 locus (p < .01) at 70 cM on mouse chromosome 5,
      respectively. A QTL identified for tau was associated (p < .05) with the D2NDS1
      marker at 45 cM on chromosome 2 near the Ea 6 marker at 46 cM associated (p <
      .05) with that reported for the period of wheel running activity in seven C x B
      RI strains (Schwartz, W.J., and Zimmerman, P., J. Neurosci. 10:3685 1990).

PMID- 8540895
TI  - Influence of dystrophin-gene mutation on mdx mouse behavior. I. Retention
      deficits at long delays in spontaneous alternation and bar-pressing tasks.
AB  - X-linked Duchenne muscular dystrophy (DMD) is frequently associated with a
      nonprogressive, cognitive defect attributed to the absence of dystrophin in the
      brain of DMD patients. The mutant mdx mouse, lacking in 427-kDa dystrophin in
      both muscle and brain tissues, is considered to be a valuable model of human DMD.
      In the present study, we compared mdx and C57BL/10 control mice and showed that
      mdx mice had impaired retention in a T-maze, delayed spontaneous alternation task
      24 h, but not 6 h, after acquisition. mdx mice were not impaired in acquisition
      of a bar-pressing task on 4 consecutive days but showed poor retention 22 days
      after the last training session. Mutants and controls showed similar behavioral
      responses in free exploration and light/dark choice situations and did not differ
      in spontaneous locomotor activity or motor coordination. Retention impairments at
      long delays in mdx mice suggest a role of dystrophin in long-term consolidation
      processes.

PMID- 8540894
TI  - Genetic analysis of anxiety-related behaviors and responses to benzodiazepine
      related drugs in AXB and BXA recombinant inbred mouse strains.
AB  - Recombinant inbred (RI) strains derived from the C57BL/6J and A/J mouse strains
      were used for behavioral studies designed to estimate the number and location of
      chromosomal loci responsible for anxiety-related behaviors and differential
      sensitivity to agonists and inverse agonists of the gamma-aminobutyric acidA
      (GABAA)/benzodiazepine receptor complex. The phenotypes of the parental inbred
      strains and of 28 RI strains were characterized for the number of transitions in
      the light<-->dark exploratory model, anxiolytic response to diazepam, vertical
      and ambulatory activities in an open field, and sensitivity to the convulsant
      properties of methyl-beta-carboline-3-carboxylate (beta-CCM). The strain
      distribution patterns and estimates of the minimal number of loci obtained for
      each trait suggest that multiple chromosomal loci contribute to differences in
      anxiety-related behavioral phenotypes and the behavioral responses to diazepam
      and beta-CCM between C57BL/6J and A/J mice. The best probabilities of linkage
      were found between the variables characterizing response to diazepam and loci on
      chromosomes 1 (Xmv-41) and 10 (D10Mit2) and between the sensitivity to the
      convulsant actions of beta-CCM and locus D15Mit5 on chromosome 15.

PMID- 8540896
TI  - Genetic evidence that ovulation reduces sexual receptivity in Drosophila
      melanogaster females.
AB  - Drosophila females start ovulation shortly after mating, and at the same time
      they become unreceptive to courting males. Both physiological changes are induced
      by the "sex-peptide" derived from the male accessory glands. It is conceivable,
      therefore, that the first effect of the peptide is to induce ovulation, and some
      signal derived from ovulated eggs makes females unreceptive. To test this
      hypothesis, I examined the mating receptivity of virgin D. melanogaster females
      homozygous for lozenge mutants that showed a high-frequency spontaneous
      ovulation. These females were reluctant to mate. However, when mature eggs were
      genetically deprived using nonallelic female sterile mutants, their receptivity
      increased significantly, although mating speed was still slower than that of
      normal virgin females. Essentially the same was found with the females that were
      ectopically expressing the sex-peptide gene. The results indicate that ovulation
      induced by the sex-peptide has an effect of reducing the sexual receptivity of
      mated females.

PMID- 8540897
TI  - [Protein composition of venoms from several species of tropical ants and their
      effect on mitochondrial H+-ATPase].
AB  - Protein compositions of venoms of South-American stinging ants, Ectatomma
      tuberculatum, Paraponera clavata (subfamily Ponerinae), and "tangarana" were
      analyzed. The venom of E. tuberculatum displayed the most complex protein
      composition (more than 15 polypeptides). The water-soluble fraction of the venoms
      of P. clavata and "tangarana" contained acidic proteins (pI < 3.5 to 5.2),
      whereas the venom of E. tuberculatum contained predominantly basic proteins (pI 8
      to > 9.5). N-Terminal residues and N-terminal sequences of a number of
      polypeptides were determined. High-molecular-mass polypeptides of the P. clavata
      venom slightly stimulated the ATPase activity of mitochondrial F1-ATPase. Low
      molecular-mass nonprotein components of this venom significantly inhibited the
      ATPase activity of submitochondrial particles and F1-ATPase from bovine heart
      mitochondria. The venoms of E. tuberculatum and "tangarana" produced no effect on
      the ATPase activity.

PMID- 8540898
TI  - [Refinement of the spatial structure of neurotoxin II from Naja naja oxiana
      venom].
AB  - A set of 19 conformations of the neurotoxin II from Naja naja oxiana was
      determined by conformational energy minimization using constraints derived from
      experimental 1H NMR data. The pairwise average root-mean-square deviations were
      0.86 A for the backbone heavy atoms and 1.48 A for all heavy atoms of these
      conformations. A model of the neurotoxin II dimer is proposed to account for the
      relatively slow deuterium exchange rates of the Val45 and Leu51 amide protons,
      which are exposed to the solvent in the calculated conformations of monomeric
      neurotoxin II. Both the monomeric and dimeric models of neurotoxin II may be
      useful for detailed studies of the functional, hydrophobic, and electrostatic
      properties of this molecule.

PMID- 8540899
TI  - [Structural organization of rimorphin and its synthetic analogs].
AB  - The spatial structure and conformations of rimorphin were investigated using
      theoretical conformational analysis. The spatial organization of the peptide can
      be described by a set of 11 low-energy conformations of the backbone. By solving
      the reverse conformational problem, a number of modified amino acid sequences
      ([Ala2], [Ala3], [MePhe9], [MeLys10], [MeVal11], and [MeVal12]-analogs of
      rimorphin) were determined that have spatial structures corresponding to the set
      of low-energy conformations and should, therefore, possess physiological
      activity.

PMID- 8540900
TI  - [Synthesis of stearoyl derivatives of proline-containing hydrophobic peptides].
AB  - Hydrophobic stearoyl derivatives of proline-containing di- and tripeptides and
      their deuterated analogs were synthesized. It was shown by NMR spectroscopy that
      cis-trans-equilibrium around an X-Pro peptide bond is displaced towards trans
      conformers for compounds containing a Ste-Pro fragment as opposed to the
      compounds containing Boc-Pro or Gly-Pro fragments.

PMID- 8540901
TI  - [Expression of a synthetic gene for human angiogenin in a recombinant vaccinia
      virus].
AB  - The gene for angiogenin was cloned into vaccinia virus genome. The recombinant
      virus expressing angiogenin was obtained. The level of protein synthesis directed
      by the recombinant virus was analyzed by immunoblotting using monoclonal
      antibodies against human angiogenin.

PMID- 8540902
TI  - [Acyclic nucleoside analogs: synthesis and cytotoxic properties of acyl
      derivatives of 3'(5')-amino-3'(5')-deoxy-2',3'-secoadenosine].
AB  - Interaction of 3'-amino-3'-deoxy-2',3'-secoadenosine with the N
      hydroxysuccinimide esters of nicotinic or quinaldic acids and with 1
      nitroanthraquinone-2-carboxylic acid in the presence of 2-ethoxy-1-ethoxy
      carbonyl-1,2-dihydroquinoline led to the corresponding amides. To obtain 5'
      modified 2',3'-secoadenosine analogs, 5'-deoxy-5'-nicotinoylamido-, 5'-deoxy-5'
      (quinoline-2- carbonylamido)-, and 5'-deoxy-5'-[3-(3
      indolyl)propionylamido]adenosine were subjected to the periodate oxidation-
      sodium borohydride reduction procedure. Structures of the synthesized compounds
      were was confirmed by 1H NMR spectroscopy, 2',3'-Diamino-2',3'-deoxy-, 3'-deoxy
      3'-(quinoline-2-carbonylamido)-, and 5'-deoxy-5'-[3-(3-indolyl)propionylamido]
      2',3'-secoadenosines+ ++ exhibited a cytotoxic effect on CaOv cells in vitro
      (CE50 10-30 microM).

PMID- 8540903
TI  - [Synthesis and biological properties of pyrimidine 2'-deoxynucleosides modified
      by a residue of quinaldic acid].
AB  - O-Quinaldoyl derivatives of thymidine, 2'-deoxyuridine, and 5-trimethylsilyl-2'
      deoxyuridine were synthesized. 5'-Deoxy-5'-(quinoline-2-carbonylamino)- and 5'
      deoxy-5'-[(quinoline-2-carbonylamino)butyroylamino]thymidine were obtained by the
      reaction of 5'-amino-5'-deoxythymidine with pentafluorophenyl ester of quinaldic
      acid, or with 4-(quinoline-2-carbonylamino)butyric acid. Antiproliferative
      properties in respect to CaOv cells in vitro were found in most of the
      synthesized quinaldoyl derivatives of nucleosides (CE50 approximately 10(-5) M).
      3'-O-Quinaldoylthymidine exhibited an antitumor activity in vivo. The interaction
      of 3'- and 5'-O-quinaldoyl- as well as 3',5'-di-O-quinaldoylthymidine with DNA
      was investigated by the method of fluorescent probes.

PMID- 8540904
TI  - [Determination of phenobarbital by solid-phase immunoenzyme analysis. Choice of
      optimal strategy].
AB  - Two variants (direct and indirect) of enzyme linked immunosorbent assay (ELISA)
      of phenobarbital are compared. Both techniques were developed on the basis of the
      same monoclonal antibodies, and horse radish peroxidase was used as the label in
      both cases. When microtitration plates are used as the solid phase, indirect
      ELISA, in which phenobarbital of the sample competes with phenobarbital sorbed on
      plates in the form of a conjugate with protein for the binding with peroxidase
      labeled antiphenobarbital antibodies, is preferable. In indirect ELISA, the
      sample volume was 5 microliters, the time of assay was 40 min, the variability
      coefficient was < 8%.

PMID- 8540905
TI  - ESBRA 1994 Award Lecture. Phosphatidylethanol formation: specific effects of
      ethanol mediated via phospholipase D.
AB  - Phosphatidylethanol is a unique phospholipid which is formed in cell membranes
      only in the presence of ethanol. The reaction is catalysed by phospholipase D, an
      enzyme that normally catalyses the hydrolysis of phospholipids leading to the
      formation of phosphatidic acid. However, phospholipase D also utilizes short
      chain alcohols as substrates resulting in the formation of the corresponding
      phosphatidylalcohol. This is a specific mechanism through which ethanol may
      interact with cell function. Phospholipase D is activated by several different
      receptors and has during recent years been suggested to play a role in cellular
      signalling. Secretory processes as well as long-term changes of cell function
      have been associated with the activation of phospholipase D. Since ethanol
      competes with water as a substrate for this enzyme, phosphatidylethanol is formed
      at the expense of the normal lipid product, phosphatidic acid, in an ethanol
      concentration-dependent manner. Therefore, the phospholipase D-mediated signal
      transduction diverges from production of the normal signalling lipid in the
      presence of ethanol. However, phosphatidic acid may also be formed by other
      pathways and their relative contribution to the formation of this lipid depends
      on the cell and receptor type. Thus, it is important to identify the signalling
      systems where phospholipase D dominates the lipid messenger production since
      these may be especially vulnerable to ethanol. In addition to a change in
      phospholipase D-mediated signal transduction, accumulation of phosphatidylethanol
      in cell membranes may also induce disturbances in cell function. Significant
      amounts of this abnormal phospholipid have been detected after ethanol exposure
      in brain and other organs from rat, in cultured cells as well as in human blood
      cells. The degradation of phosphatidylethanol is relatively slow and it remains
      in the cells after ethanol has disappeared. It is possible that an abnormal
      phospholipid that accumulates in cell membranes affects membrane-associated
      processes. Phosphatidylethanol is a lipid with a small, anionic head group and
      its biophysical properties are different compared with other phospholipids.
      Moreover, this lipid has been demonstrated to influence membrane characteristics,
      enzyme activities and levels of signalling molecules. Thus, both the inhibition
      of phospholipase D-mediated signal transduction and the accumulation of
      phosphatidylethanol represent possible pathways through which ethanol may disturb
      cell function.

PMID- 8540906
TI  - A good man's fault: alcohol and Irish people at home and abroad.
AB  - Long-standing stereotypes portray Irish people as prone to use alcohol to excess.
      This review traces the historical origins of those stereotypes, and examines
      evidence drawn from a range of secondary sources in Ireland and Britain about
      alcohol consumption, attributed hospital admissions and mortality. The available
      data indicate that the 'problem' of Irish drinking and Irish attitudes to alcohol
      are not as straightforward as traditionally supposed. Far from the stereotypical
      image of the Irish embodied in the ubiquitous drunk male labourer, rates of
      abstinence from alcohol are higher in Ireland than in Britain. Amongst migrants,
      the Irish are no more likely to consume alcohol than the indigenous population.
      However, those Irish people who do drink alcohol do so at generally higher levels
      than their British born counterparts. Analysis of combined years' data from the
      General Household Survey indicates first that people of Irish birth or parentage
      are no more likely than the British born to use alcohol at all. However, if they
      make use of alcohol at all, members of the Irish groups were more likely than the
      British born to consume alcohol at levels greater than 14 or 21 units per week.
      Both the review and the data presented suggest that a more complex understanding
      of the dynamics and nature of Irish drinking needs to be developed.

PMID- 8540907
TI  - Additional proof of reduction of ethanol absorption from rat intestine in vivo by
      high acetaldehyde concentrations.
AB  - We investigated intestinal ethanol absorption in rats pretreated with saline,
      cyanamide, 4-methylpyrazole and cyanamide + 4-methylpyrazole. The value of the
      absorption rate constant in the cyanamide-pretreated group with high acetaldehyde
      levels was the lowest among the four groups, but there were no significant
      differences among the remaining groups. We found that high acetaldehyde
      concentration itself clearly reduces intestinal ethanol absorption.

PMID- 8540908
TI  - An unusual case of central pontine myelinolysis.
AB  - Central pontine myelinolysis (CPM) is a rare complication of alcoholism. There
      have been recent reports that hyponatremia and its rapid correction are of
      aetiological significance in the development of CPM. We describe the case of a 47
      year-old alcoholic who developed CPM and subsequently recovered. Alcoholic and
      psychiatric patients are at risk for CPM and clinicians need to have a high index
      of suspicion to diagnose this condition.

PMID- 8540909
TI  - Women alcoholics--social, demographic and clinical characteristics in a Brazilian
      sample.
AB  - We compared 115 female and 115 male Brazilian alcoholics in terms of their social
      and demographic characteristics, as well as other characteristics associated with
      alcohol consumption. Women both began drinking and increased their consumption
      later than men. The incidence of attempted suicide was higher among women.
      Females used less illicit drugs. Male alcoholics were more frequently born in the
      city of Sao Paulo. As for adherence to treatment in an out-patient clinic, no
      significant differences were found between the sexes 3, 6, 9 and 12 months after
      initiation of treatment.

PMID- 8540910
TI  - Role of alcoholic beverages in essential hypertensive patients.
AB  - To evaluate the importance of alcohol and other environmental factors in
      essential hypertensives, we conducted a cross-sectional study on 627 patients
      (322 women, 305 men) subdivided in four subgroups according to sex and presence
      or absence of drug therapy, to evaluate differences due to drugs and changes in
      life style. Multiple regression analyses were run where systolic and diastolic
      blood pressures were considered as separate dependent variables with the
      following independent variables: age, body mass index, physical activity, alcohol
      and coffee consumption, smoking, educational level; considered as continuous or
      categorical variables. eighty-eight per cent of all patients showed a moderate
      low alcohol intake (1-50 g/day); wine was the preferred beverage. We found a
      negative independent relationship between mild/moderate alcohol consumption
      levels and systolic blood pressure in untreated men and untreated women, and no
      relationship between alcohol and diastolic blood pressure in all subgroups
      considered. Body mass index and age were positively associated with both systolic
      and diastolic blood pressure. Our data suggest that mild to moderate alcohol
      consumption does not affect blood pressure control in either treated or untreated
      hypertensive patients.

PMID- 8540911
TI  - Prevalence of alcohol problems among adult somatic in-patients in Naples.
AB  - The aim of this cross-sectional study was to determine the prevalence of alcohol
      problems among adult somatic in-patients in urban hospitals of Naples. The
      patients were screened with a structured questionnaire regarding life style.
      After discharge, the patient records were examined and the hospital discharge
      diagnoses were registered. A patient was considered having an alcohol problem if
      one or more of the following criteria were fulfilled: (1) a Michigan Alcoholism
      Screening Test score at or above five; (2) a self-reported daily consumption for
      at least 2 years of at least 60 g of ethanol for males and 36 g for females; (3)
      an alcohol-related discharge diagnosis. The prevalence of patients with alcohol
      problems was significantly (P < 0.01) higher among male (43.8%, 95% confidence
      limits, 37.6-50.2%) than among female patients (14.8%, 95% confidence limits, 9.6
      21.4%). There were no significant differences among the different types of
      somatic departments regarding the prevalence of alcohol problems when gender was
      considered. Patients with alcohol problems differed significantly from those
      without alcohol problems regarding a number of variables: the former drank
      significantly more alcohol, smoked for more years, and had a higher prevalence of
      alcohol problems in the family. It is concluded that alcohol problems among in
      patients are as prevalent in Naples as in other industrialized countries, that it
      is often not registered among discharge diagnoses, and that the problems are more
      prevalent in males than in females, irrespective of the type of department.

PMID- 8540912
TI  - Effect of acute alcohol ingestion on mineral metabolism and osteoblastic
      function.
AB  - Alcohol abuse can induce osteopenia in some subjects. In order to study the
      effect of a single dose of alcohol on mineral metabolism and osteoblastic
      function, we have measured calcium, phosphate, parathyroid hormone midmolecule
      (PTHm), parathyroid hormone intact molecule (PTHi) and bone-gla-protein (BGP) in
      serum of 8 healthy men after the ingestion of a single dose of alcohol (0.6 g/kg
      body weight). Urinary calcium and magnesium were also measured. After alcohol
      intake, both serum PTHm and PTHi were decreased, as well as serum BGP. Serum
      phosphate and urinary calcium and magnesium were increased. An inverse
      significant correlation was found between PTHi and serum phosphate (r = 0.42; p <
      0.02). Our data show that acute alcohol ingestion lowers serum PTH and BGP in
      humans, suggesting an inhibitory effect on parathyroid and osteoblastic function.
      These changes and the alcohol-induced transient hypercalciuria could contribute
      to the development of bone disease associated with chronic alcohol abuse.

PMID- 8540913
TI  - Changes of G-protein levels in platelet membranes from alcoholics during short
      term and long-term abstinence.
AB  - The levels of G alpha i2-protein and the G beta gamma-heterodimer were measured
      in platelet membranes of non-alcoholics, non-alcoholics after an ethanol load (1
      g/kg body weight) and of alcoholics under various conditions. The findings were
      correlated with the activation of the adenylyl cyclase (AC) by various agents.
      The activation of AC was facilitated by acute ingestion of ethanol. This could
      not be explained by changes of the G-proteins determined because the levels of
      the G alpha i2-protein increased, whereas those of the G beta gamma-proteins
      remained in the control range. The alcoholics were divided into two groups on the
      day of admission: those with ethanol still present in the blood (intoxicated
      alcoholics) and those acutely withdrawn within the last 48 h (ethanol absent from
      the blood). The intoxicated alcoholics had elevated G alpha i2-protein levels in
      contrast to the acutely withdrawn patients, who did not. This observation
      suggests rapid changes of the G-protein levels. By analysing the inhibitory
      efficacy of the G-proteins on AC, it was found that the concentration of the G
      beta gamma-heterodimer, but not that of the G alpha i2-proteins, correlated with
      the inhibitory efficacy. The basal activity of the AC was reduced as well as the
      activation by some compounds. Eight days later (short-term withdrawal) both the
      levels of G alpha i2 and G beta gamma were elevated. Again, the inhibitory
      efficacy of the G-proteins correlated with the G beta gamma-heterodimer levels
      but not with those of the G alpha i2-protein. Furthermore, the changes of the G
      beta gamma-protein levels between the first and the eighth day correlated with
      the changes of the inhibiting efficacy. Only a trend was observed with respect to
      a lowered basal activity if compared with the intoxicated non-alcoholics. The
      activation of AC by guanylylimidyldiphosphate [Gpp(NH)p] and Gpp(NH)p + ethanol
      (200 mM in vitro) was still reduced. Observations after 3 and 6 months of
      abstinence demonstrated elevated G alpha i2- and G beta gamma-protein levels.
      This suggests residual marker properties of the G-proteins whereby the activity
      of AC was normal. Only the reduced stimulation by Gpp(NH)p + ethanol in vitro
      (200 mM), compared with the respective stimulation of AC of intoxicated non
      alcoholics, suggested some residual disturbances of the signal transduction
      during long-term abstinence.

PMID- 8540914
TI  - The association between alcohol consumption and suicide and homicide rates: a
      study of 13 nations.

PMID- 8540915
TI  - [Special issue of pathology of liver].

PMID- 8540916
TI  - [Classification of chronic hepatitis].

PMID- 8540917
TI  - [Virus detection in the liver].

PMID- 8540918
TI  - [Alcoholic liver disease. From morphology to pathogenesis].

PMID- 8540919
TI  - [Current approach to hepatic carcinogenesis. From cirrhosis to hepatocellular
      carcinoma].

PMID- 8540920
TI  - [Non-neoplastic diseases of the intrahepatic biliary tracts in adults].

PMID- 8540921
TI  - [Histologic diagnosis of neonatal cholestasis].

PMID- 8540922
TI  - [Diagnosis of hepatic siderosis].

PMID- 8540923
TI  - [Liver fibrosis].

PMID- 8540924
TI  - [Role of fine needle puncture in the diagnosis of a hepatic mass].

PMID- 8540925
TI  - [Immunohistochemistry in liver pathology].

PMID- 8540926
TI  - [Pathology of liver graft viral reinfection].

PMID- 8540927
TI  - Alpha 1-antitrypsin deficiency and pregnancy.
AB  - Alpha1-antitrypsin deficiency is an inherited pulmonary disorder which results
      from a deficiency of a major plasma protease inhibitor. The onset and severity of
      symptoms vary widely and depend on the genotype and whether the patient smokes
      cigarettes. Alpha1-antitrypsin in pregnancy has only been previously reported
      twice. Our patient had a functional serum alpha1-antitrypsin level which was 15%
      of normal but was clinically asymptomatic and she did not smoke. Her genotype
      revealed a non-ZZ pattern. Her obstetric history was complicated by preterm labor
      in each of her five ongoing pregnancies. Alpha1-antitrypsin deficiency is
      inherited via two codominant autosomal genes. Although there is great variability
      in severity of disease, seriously affected patients may have emphysema and
      hepatic abnormalities. Patients with non-ZZ genotypes or who are heterozygotes
      may have favorable pregnancy outcomes.

PMID- 8540928
TI  - Immunoglobulin subclass concentration in preterm infants treated prophylactically
      with different intravenous immunoglobins.
AB  - The most immature infants have critically low concentrations of all
      immunoglobulin G (IgG) subclasses, associated with a higher risk for pyogenic,
      respiratory, and meningeal infection. Selective IgG subclass deficiency is an
      established indication for intravenous immunoglobulin (IVIG) substitution.
      However, considering that therapeutic efficacy of IVIG is dependent on its
      pharmacokinetics, we studied peak and trough IgG subclass serum levels during the
      neonatal period (28 days) in a group of 34 healthy preterm babies (30.2 +/- 2
      weeks gestational age (GA) and 1065 +/- 210 g birthweight (BW) treated
      prophylactically with three daily standard doses of two different IVIG
      preparations: Sandoglobulin (SG) (0.5 g/kg/day) and Pentaglobin (PG) (5
      mL/kg/day). IgG subclass levels were assayed by radioimmundiffusion (RID) before
      treatment (day 1) and at days 3, 5, 7, 14, and 28 of life. Statistical analysis
      was performed by paired t test. In the first week of life only (days 3, 5, 7),
      for both IVIG preparations, subclass levels were higher than pretreatment values:
      IgG1, 4.6 +/- 1.7 versus 5.6 +/- 1.6 g/L; IgG2, 1.6 +/- 0.8 versus 2.1 +/- 0.6
      g/L; IgG3, 0.2 +/- 0.7 versus 0.3 +/- 0.1 g/L; IgG4, 0.3 +/- 0.1 versus 0.9 +/-
      0.1 g/L (p < 0.05). During this time (7 days) IgG2 levels were higher in the SG
      group and IgG4 was higher in the PG group (p < 0.05). This study shows
      pretreatment IgG subclass levels 14 days after treatment and different patterns,
      depending on the used preparation. We conclude that prospective clinical trials
      should include the study of target serum levels and timing of IVIG administration
      not only for IgG but also for IgG subclasses.

PMID- 8540929
TI  - Severe preeclampsia with fulminant and extreme elevation of aspartate
      aminotransferase and lactate dehydrogenase levels: high risk for maternal death.
AB  - We report a subgroup of patients with fulminant hemolysis, elevated liver
      enzymes, low platelet count (HELLP) syndrome, manifesting extreme elevation of
      aspartate aminotransferase (AST; SGOT) and lactate dehydrogenase (LDH) levels and
      abnormal mental status. These gravidas are at high risk for mortality. Only four
      patients treated by the authors over a 10-year period have had AST more than 2000
      IU/L and LDH more than 3000 IU/L in the HELLP syndrome. This report is based on
      retrospective chart review. All patients manifested disordered mental status,
      jaundice, intense hemolysis, and extreme hypertension. One patient had developed
      multiple organ system failure, was moribund at initial perinatal consultation,
      and died. The three others were treated with aggressive afterload reduction and
      plasma infusion or plasmapheresis; two survived. Fulminant HELLP syndrome occurs
      rarely, but marks a group of patients at high risk for mortality. Optimal therapy
      is unclear; early intervention, including afterload reduction, volume expansion,
      and consideration of plasma infusions or plasmapheresis, is recommended.

PMID- 8540931
TI  - Endocardial fibroelastosis: an unusual cause of pulmonary hypertension in
      pregnancy.
AB  - Pulmonary hypertension due to endocardial fibroelastosis is usually diagnosed
      during infancy and childhood and is almost uniformly lethal when severe. Since
      females with this disorder rarely reach reproductive age, no cases of successful
      pregnancy in the presence of this severe cardiopulmonary disease have been
      reported. A 23-year-old Caucasian primigravida with a history of congenital
      endocardial fibroelastosis and severe pulmonary hypertension presented at 20
      weeks' gestation. Following cardiac catheterization, the pregnancy was managed
      with bed rest, oral theophylline and digoxin, and low-flow oxygen therapy. After
      spontaneous onset of labor at 35 weeks, invasive hemodynamic monitoring and
      epidural anesthesia were initiated. Worsening of maternal pulmonary artery
      pressures postpartum was relieved by intravenous nitroglycerin infusion. Recent
      advances in medical care have resulted in more women with endocardial
      fibroelastosis reaching reproductive age. Successful pregnancy outcome is
      possible using established techniques of modern obstetric care.

PMID- 8540930
TI  - Recombinant human erythropoietin in the treatment of anemia of prematurity.
AB  - Seventy premature infants (birthweight 1.75 kg or less, gestational age 33 weeks
      or less) with hemoglobin less than 10 g/dL and hematocrit less than 30% were
      studied and randomly divided into three groups. All of them received oral
      elemental iron 3 mg/kg/day and vitamin E 5 mg/kg/day during the study period.
      Recombinant human erythropoietin (rHuEPO) 150 U/kg was administered intravenously
      twice a week for 4 weeks in group A (26 infants). Infants in group A received a
      total of 4 erythrocyte transfusions because of frequent apnea. Infants in group B
      (25 infants) received erythrocyte transfusion when their hemoglobin levels was
      less than 10 g/dL with signs and symptoms (including tachycardia, tachypnea, poor
      feeding, apnea, poor weight gain) attributed to anemia or who had a hemoglobin
      less than 8 g/dL even if asymptomatic. Infants in group B received a total of 36
      erythrocyte transfusions. Infants in group C (19 infants) were assigned to a non
      rHuEPO and nontransfusion group. Three of the 19 premature infants in group C
      received erythrocyte transfusions later because of frequent and prolonged apneic
      episodes and were excluded from this study. Our data revealed that reticulocyte
      and serum erythropoietin values were higher (p < 0.01) in rHuEPO-treated group
      than transfusion group and hemoglobin and hematocrit values were lower in group C
      than the other two groups during the rHuEPO treatment period. No significant
      difference (p > 0.05) was found in neutrophil and platelet counts among these
      three groups. Serum ferritin values were found lower in the rHuEPO-treated group
      than the other two groups. Lower weight gain was found in infants in group C. We
      conclude that rHuEPO administration can reduce the need for blood transfusion.
      Poor weight gain can be found in infants with anemia of prematurity who do not
      receive rHuEPO or blood transfusion therapy.

PMID- 8540933
TI  - Incidence, timing, and follow-up of periventricular leukomalacia.
AB  - Screening cranial ultrasounds were performed on 115 very low birthweight infants
      during the first week of life. Fourteen infants (12%) developed changes of
      periventricular leukomalacia. All 14 weighted 1100 g or less at birth. Eight
      infants' initial studies were normal, four had intraventricular hemorrhage, and
      two had periventricular echo densities. Cystic periventricular leukomalacia
      developed between 17 and 104 days of age and occurred later in those infants
      whose initial study was normal. There were tone abnormalities in 11 of the 12
      infants who received developmental follow-up. Severe cognitive delays were common
      in the older infants. This study demonstrates the need for late ultrasound
      screening even in the presence of initial normal ultrasound examinations.

PMID- 8540932
TI  - Ampicillin/sulbactam versus ampicillin alone for cesarean section prophylaxis: a
      randomized double-blind trial.
AB  - To study the effectiveness of anaerobic coverage in prevention of postpartum
      endometritis in women undergoing nonelective cesarean sections, we conducted a
      randomized prospective double-blind study of women undergoing cesarean sections
      and requiring antibiotic prophylaxis from April 1, 1989, through December 31,
      1990. Ninety-four patients were enrolled in the study. Forty-five patients
      received ampicillin alone and 46 received ampicillin in conjunction with
      sulbactam. All patients were evaluated prior to surgery and in the postoperative
      period. Ninety-one patients completed the study and their records were analyzed.
      Patients were divided into two groups depending on the presence or absence of
      ruptured membranes. Seventy-five percent of patients had ruptured membranes.
      Failure of prophylaxis and subsequent endometritis was documented in 8.8% of
      patients who received ampicillin and sulbactam and 35.3% of patients who received
      ampicillin alone. This difference was statistically significant (p < 0.02). In
      conclusion, single-dose ampicillin and sulbactam provides better prophylaxis than
      single-dose ampicillin in women undergoing cesarean section with rupture of
      membranes.

PMID- 8540934
TI  - Myocardial infarction and coronary artery dissection in pregnancy.
AB  - Myocardial infarction associated with pregnancy is a relatively rare event,
      usually related to maternal risk factors for ischemic heart disease such as
      hypertension and diabetes mellitus. Coronary artery dissection represents an even
      more uncommon event and generally occurs in peripartum women without predisposing
      risk factors. A 31-year-old patient's postpartum course was complicated by the
      development of probable acute fatty liver of pregnancy followed by myocardial
      infarction and coronary artery dissection. The acute fatty liver of pregnancy and
      the cardiac event in our patient may both be vasospastic events related to
      vascular hypersensitivity.

PMID- 8540935
TI  - Methemoglobinemia associated with prilocaine use in neonatal circumcision.
AB  - A term, 2500 g infant was circumcised at 2 days of age. The circumcision was
      uneventful, with no excessive bleeding. Analgesia was provided by prilocaine, 0.5
      cc, and subsequently, the neonate developed methemoglobinemia. Alternatives to
      analgesia with prilocaine are discussed.

PMID- 8540936
TI  - Antenatal diagnosis and management of fetomaternal alloimmune thrombocytopenia.
AB  - Fetomaternal alloimmune thrombocytopenia (FMAT) arises from maternal-fetal
      platelet antigen incompatibility, which stimulates the production of maternal
      immunoglobulin G (IgG) platelet-specific antibody. Transplacental passage of this
      antibody results in fetal platelet destruction and consequent thrombocytopenia.
      Sequelae of thrombocytopenia may be observed in both the fetus and neonate with
      intracranial hemorrhage occurring in approximately 10 to 30% of affected infants.
      No antenatal universal screening test is currently available to detect the 50% of
      cases occurring in the first pregnancy. The recurrence rate in subsequent
      pregnancies is 75 to 85%, with a tendency to increasing disease severity.
      Paternal platelet genotyping is recommended to assist in risk counseling
      following an affected pregnancy. Prenatal therapeutic strategies are aimed at
      elevating the fetal platelet count in affected pregnancies and thus decreasing
      hemorrhagic sequelae. The most effective treatment regimen is uncertain, but
      encouraging results are reported with the use of maternal intravenous gamma
      globulin. We report our experience in the antenatal diagnosis and management of
      FMAT.

PMID- 8540937
TI  - Life-threatening inadvertent positive end-expiratory pressure.
AB  - Inadvertent positive end-expiratory pressure (PEEP) is a potential cause of lung
      overdistension and impaired gas exchange in ventilated infants. It can be
      extremely difficult to diagnose clinically and if unrecognized can be life
      threatening. Measurement of lung function can lead to the recognition of
      inadvertent PEEP, allowing appropriate ventilator adjustment with immediate
      substantial improvement in clinical state. Lung function measurements can help to
      optimize ventilation and may improve clinical outcome.

PMID- 8540938
TI  - Gallbladder perforation in pregnancy.
AB  - Gallbladder perforation is an infrequent but potentially fatal disease. It is
      extremely rare during pregnancy. We report two cases of gallbladder rupture in
      the immediate postpartum period and review the literature. The first patient was
      a 28-year-old polysubstance abuser who presented at 29 weeks' gestation with
      generalized abdominal pain and ascites. Over a 48-hour period, her abdominal pain
      increased, and preterm labor and delivery occurred. She had an exploratory
      laparotomy the day after delivery for persistent abdominal pain and ascites, and
      a ruptured, gangrenous gallbladder was found. This patient died secondary to
      complications of the disease. Our second patient had a history of cholelithiasis
      and developed abdominal pain on the third postpartum day. Three days later, she
      was taken for exploratory laporatomy and was found to have a ruptured
      gallbladder. She did well postoperatively. The signs and symptoms of a ruptured
      gallbladder can be quite confusing in pregnancy. Ultrasonography, ascitic fluid
      analysis, computed tomography, and magnetic resonance imaging are useful adjuncts
      in diagnosis. A high index of suspicion, prompt recognition, and early surgical
      intervention are the mainstays of therapy.

PMID- 8540939
TI  - Correlation of fetal heart rate decelerations following acoustic stimulation with
      perinatal outcome.
AB  - This was a retrospective study of acoustic stimulation response and perinatal
      outcome of 688 fetuses undergoing nonstress testing. Acoustic stimulation was
      performed within 7 days of delivery, and responses were classified based on the
      presence of an acceleration, deceleration, or both. Responses were correlated
      with perinatal outcome. Abnormal outcome was defined as: cesarean section for
      nonreassuring fetal heart rate patterns with an acidotic umbilical artery cord
      gas; delivery at less than 32 weeks for nonreassuring antenatal fetal testing;
      meconium aspiration syndrome or mechanical ventilation at 36 weeks or greater;
      neonatal seizures; 5-minute Apgar score less than 7; and stillbirth. Fetuses who
      demonstrated deceleration responses were significantly more likely to have
      abnormal perinatal outcomes when compared with those with acceleration responses
      (p < 0.001). Although combination acceleration-deceleration responses were more
      often associated with abnormal perinatal outcome when compared with pure
      acceleration responses, differences were not significant. A deceleration response
      following acoustic stimulation is associated with increased risk for adverse
      perinatal outcome and may merit further evaluation.

PMID- 8540940
TI  - Fetal varicella syndrome with manifestations limited to the eye.
AB  - The manifestations of fetal varicella syndrome usually involve several organ
      systems, including skin, ocular, neurologic, gastrointestinal, and genitourinary.
      Although ocular anomalies have been reported to be as high as 68%, manifestations
      limited to the eyes is extremely rare. Herein we report the case of fetal
      varicella syndrome with no clinical signs other than esotropia and a
      chorioretinal scar.

PMID- 8540941
TI  - Urinary calcium to creatinine ratio for predicting preeclampsia.
AB  - Urinary calcium excretion decreases in preeclampsia. To determine the
      predictability of preeclampsia with hypocalciuria, we investigated the calcium to
      creatinine ratio and the calcium level of a spot urine sample in 56 primigravid
      patients aged less than 25 years. Of these 56 cases, 44 remained normotensive and
      preeclampsia developed in eight cases. There were four cases of gestational
      hypertension and they are not included in the statistical analysis. The mean age,
      the mean gestational age at entrance into the study, the mean urine calcium
      concentration, the mean birthweight, and the mean gestational age at delivery
      were similar between the normotensive and preeclamptic groups. The mean calcium
      to creatinine ratio is found to be significantly lower in the preeclamptic group
      (0.0475 +/- 0.0260) compared with the normotensive group (0.1466 +/- 0.1353; p <
      0.0001). A cutoff level of 0.066 for the calcium to creatinine ratio with the use
      of a receiver operator curve yielded a sensitivity of 75%, a specificity of 86%,
      and a positive and negative predictive value of 55% and 95%, respectively. The
      results of this study suggest that a single urine calcium to creatinine ratio
      might be an effective marker for predicting preeclampsia in a high-risk
      population.

PMID- 8540942
TI  - Factors predictive of recurrent gestational diabetes diagnosed before 24 weeks'
      gestation.
AB  - The purpose of this study was to determine which patient and pregnancy
      characteristics in the first pregnancy complicated by gestational diabetes
      mellitus (GDM) were associated with the diagnosis of GDM before 24 weeks'
      gestation in a subsequent pregnancy--early recurrent GDM. The case notes of 180
      women who previously had GDM diagnosed and who had glucose tolerance tests
      performed before 24 weeks' gestation in their next ongoing pregnancy were
      reviewed. Factors examined included severity of GDM, insulin requirement, racial
      origin, macrosomia, obesity, age, family history of diabetes, preeclampsia, and
      parity. Multivariate analysis showed that women with early recurrent GDM were
      more likely, in their first pregnancy with GDM, to have needed insulin (odds
      ratio [OR] 11.26; 95% confidence interval [CI] 2.02 to 62.65), to be more often
      of non-Northern European origin (OR, 5.53; 95% CI, 2.46 to 12.44), to have had a
      macrosomic infant (OR, 4.01; 95% CI, 1.40 to 11.49) or severe GDM (OR, 3.52; 95%
      CI, 1.60 to 7.76), and were more often 30 years or more of age (OR, 2.27; 95% CI,
      1.05 to 4.90). Obesity, family history, fasting plasma glucose levels, and parity
      were not significant risk factors. However, even without any of the significant
      risk factors, logistic regression modeling suggested that a woman who has had GDM
      in a previous pregnancy has a 5.1% (95% CI, 2.2 to 11.6%) chance of having early
      recurrent GDM. We therefore continue to recommend that all women who have had GDM
      diagnosed previously should have glucose tolerance testing performed early
      (before 24 weeks' gestation) in any future pregnancies.

PMID- 8540943
TI  - Continuous maternal glucose infusion during labor: effects on maternal and fetal
      glucose and lactate levels.
AB  - Fetal and neonatal glucose and lactate levels and acid-base balance after
      continuous maternal infusion of 5% dextrose at 180 mL/h (9 g/h) was compared with
      0.9% saline solution in a prospective, randomized study from selected monitored
      labors. An infusion of 5% dextrose produced significantly increased glucose
      levels in maternal (p < 0.01), cord artery (p < 0.01), and cord vein (p < 0.001)
      blood. An increased maternal insulin level was also present (p < 0.05), but no
      differences in cord insulin levels were observed. beta-Hydroxybutyrate was lower
      in maternal (p < 0.05) and cord vein (p < 0.01), but not in cord artery blood,
      after maternal dextrose infusion. No significant changes occurred in blood
      lactate levels between the two groups in either mother, fetus, cord, or neonate.
      Acid-base balance in cord blood did not differ between the two groups. Maternal
      infusion of 5% dextrose at 180 mL/h (9 g/h), compared with saline solution,
      produces higher glucose levels in both mother and fetus, but increased insulin
      concentrations only in the mother. Dextrose infusion also lowers beta
      hydroxybutyrate in maternal and cord vein blood. No differences were seen in
      lactate levels or cord acid-base balance. Both regimens seem safe according to
      risks for lactacidosis and neonatal hypoglycemia in the normoxemic, normal size
      fetus.

PMID- 8540944
TI  - Ultrasound in screening for neonatal adrenal hemorrhage.
AB  - Neonatal adrenal hemorrhage is common. Relatively large size and extensive
      vascularity of the gland results in its vulnerability to trauma and traumatic
      asphyxial injuries. The reported incidence from necropsies is 1.7 per 1000
      births. Ultrasound scans were performed on each of 8374 consecutive newborns
      delivered throughout 48 months ending December 31, 1993, in the Department of
      Obstetrics and Gynaecology. During our screening, 16 cases of adrenal hemorrhage
      (10 males and 6 females) were noted at an incidence of 1.9 per 1000. All of the
      cases of adrenal hemorrhages remained intracapsular with spontaneous resolution.
      Thirteen cases were right sided, two cases were left sided, and one case was
      bilateral. None required surgical exploration. Neonatal treatment included
      further phototherapy in 12 cases, blood transfusions in five cases, and
      antibiotics in three cases. Signs of transient adrenocortical insufficiency were
      observed in one child.

PMID- 8540945
TI  - Tolazoline-assisted Doppler echocardiography confirming normal pulmonary venous
      return in a neonate with severe persistent pulmonary hypertension.
AB  - In a critically ill neonate, pulsed and color-flow Doppler echocardiography was
      able to document normal pulmonary venous return after an intravenous dose of
      tolazoline hydrochloride. Differential diagnosis was between persistent pulmonary
      hypertension of the newborn and obstructed total anomalous pulmonary venous
      return. Once normal pulmonary venous return was clearly documented, all
      therapeutic efforts were directed at the infant's lung disease.

PMID- 8540946
TI  - Effects of low-dose aspirin therapy on plasma levels of polyunsaturated fatty
      acids: a preliminary investigation.
AB  - Polyunsaturated fatty acids play an important yet poorly understood role in
      pregnancy complications. We are interested in the effects of aspirin therapy on
      the metabolism of these compounds. To determine the effects of low-dose aspirin
      on plasma levels of polyunsaturated fatty acid precursors, we assayed linoleic,
      linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids using high
      performance liquid chromatography. Seventeen pregnant women being treated with
      aspirin therapy (81 mg/day) were evaluated between 9 and 37 weeks' gestation.
      Blood was drawn before initiation of aspirin therapy and after 3 or 4 days, and
      again after 3 or 4 weeks of therapy. We found no significant change in the plasma
      levels of fatty acids during aspirin therapy at either 3 or 4 days or 3 or 4
      weeks compared with baseline. In this group of women with preexisting disease,
      low-dose aspirin does not appear to change the plasma levels of polyunsaturated
      fatty acid precursors of eicosanoids. Data on pregnant women without hypertensive
      disorders is needed to help in understanding the role and physiology of these
      important compounds.

PMID- 8540947
TI  - The spontaneous resolution of cystic hygroma (CH), hydrops fetalis (HF), and
      fetal anemia.

PMID- 8540948
TI  - Neonatal neutrophil values in low birthweight preterm infants.

PMID- 8540949
TI  - R.E. Pattle and the discovery of lung surfactant.

PMID- 8540950
TI  - Physician's skills needed for today's complex medical practice.

PMID- 8540951
TI  - Developing a research department in a community hospital.

PMID- 8540952
TI  - Mandatory national health service in the United States: no panacea for improving
      physician mix and distribution.

PMID- 8540953
TI  - When is a school not a school?

PMID- 8540954
TI  - Will competition change the physician workforce? Early signals from the market.
AB  - Many policymakers and researchers agree that there are problems of physician
      oversupply and imbalance in specialty mix. Some have argued that these will be
      resolved as a more competitive health care market develops, predicting that cost
      conscious integrated systems will change demands for physician's services. As a
      result, physicians will experience unemployment or lower incomes, sending a
      signal to students and educators to change behavior. Although anecdotes abound,
      there has been no systematic assessment of what changes in the organization and
      financing of health care are actually doing to the physician labor market. This
      article considers potential indicators of changes and reviews what these
      indicators are now showing. Two types of change are assessed: whether increasing
      demand for generalists is changing specialty mix, and whether the market is
      creating incentives to train fewer physicians overall. There have been some
      changes in the market, but it is still too early to know whether they signal a
      departure from previous trends. Positions in generalist fields are becoming
      somewhat more attractive, but changes in incomes have been modest and the number
      of specialists continues to increase. There is also little indication that job
      opportunities for physicians are contracting.

PMID- 8540955
TI  - The range of normal.

PMID- 8540956
TI  - Taking cultural diversity seriously.

PMID- 8540957
TI  - Fostering science education and science careers at the University of Kentucky.
AB  - The Outreach Center for Science and Health Career Opportunities opened at the
      University of Kentucky Medical Center in July 1993, to provide a central site of
      coordination for the university's science education activities designed to link
      those "doing science" at the medical center with students, teachers, and the
      general population throughout Kentucky. By providing an infrastructure for
      outreach programs and by being highly visible to the public, the center attracts
      extramural funding, allows tracking of the program's students, and facilitates
      the development of science education partnerships between the university of
      Kentucky communities. The rationale for establishing the center, methods of
      operation, and impact on the region's science literacy problem are discussed.

PMID- 8540958
TI  - How doctors learn: the role of clinical problems across the medical school-to
      practice continuum.
AB  - The author proposes a theory of how physicians learn that uses clinical problem
      solving as its central feature. His theory, which integrates insights from
      Maslow, Schon, Norman, and others, claims that physicians-in-training and
      practicing physicians learn largely by deriving insights from clinical
      experience. These insights allow the learner to solve future problems and thereby
      address the learner's basic human needs for security, affiliation, and self
      esteem. Ensuring that students gain such insights means that the proper roles of
      the teacher are (1) to select problems for students to solve and offer guidance
      on how to solve them, and (2) to serve as a role model of how to reflect on the
      problem, its solution, and the solution's effectiveness. Three principles guide
      instruction within its framework for learning: (1) learners, whether physicians
      in-training or practicing physicians, seek to solve problems they recognize they
      have; (2) learners want to be involved in their own learning; and (3) instruction
      must both be time-efficient and also demonstrate the range of ways in which
      students can apply what they learn. The author concludes by applying the theory
      to an aspect of undergraduate education and to the general process of continuing
      medical education.

PMID- 8540959
TI  - Medical education research retreat.

PMID- 8540960
TI  - Family practice, internal medicine, and pediatrics as partners in the education
      of generalists.
AB  - The generalist of the future will play an integral role in the health care
      delivery system, yet the three recognized generalist specialties have developed
      and functioned along largely separate tracks. No matter what form of generalism
      evolves, family practice, internal medicine, and pediatrics must begin to
      cooperate and collaborate in developing new graduate medical education programs
      that are sufficiently flexible to meet whatever emerges in the future. They must
      devote their energies to working together, rather than competing; to emphasizing
      those parts of their programs that have similarities; and to sharing their
      knowledge, skills, attitudes, and perspectives about the care of patients. They
      must develop training experiences in which residents will obtain maximum contact
      with a wide variety of problems and patients in many different settings; a
      substantial portion of such training should be generic and virtually
      interchangeable among the three specialties. As the health care system evolves,
      so should these disciplines; they must begin to "train physicians to provide
      continuing, comprehensive and coordinated medical care to a population
      undifferentiated by gender, disease or organ system," as urged by the American
      Boards of Family Practice and Internal Medicine.

PMID- 8540961
TI  - Limiting tutorial-group size.

PMID- 8540962
TI  - A database for PBL students.

PMID- 8540963
TI  - An active-learning approach to basic clinical skills.
AB  - Within the context of comprehensive changes in the preclinical curriculum at
      Northwestern University Medical School, the authors sought to create an active
      learning approach to teaching the basic clinical skills of communication,
      physical examination, and diagnostic reasoning. This approach is built upon the
      premise that repetitive practice using a structured database, which is emphasized
      in traditional curricula, is necessary but not sufficient for students' early
      development as clinicians, as it marginalizes essential areas of discourse and
      restricts students' understanding of the scope of the medical encounter.
      Accordingly, this clinical skills curriculum incorporates small-group, patient
      instructor, and peer-observation formats to encourage critical thinking and
      reflection. The clinical skills units have been among the most popular aspects of
      Northwestern's new curriculum. Preliminary data suggest that the overall
      attitudes, knowledge, and clinical proficiency of students completing this
      curriculum compare favorably with those of students who progressed through the
      preclinical curriculum before the active-learning approach was introduced.

PMID- 8540964
TI  - The commerce of ideas: copyright in the digital era.
AB  - Copyright law concerns the rights of an individual to make copies of published
      works. Changes in technology, be they the introduction of the printing press or
      the proliferation of photocopy machines, affect how these "copy rights" are
      interpreted. The transmission of published works over digital networks and the
      introduction of new and relatively inexpensive ways to conduct commerce over the
      same networks will have a profound effect on how medical school faculty protect
      their own published works and how they make use of the published works of others.
      When copyright law moves from tangible objects such as books and journals to
      intangible bits carried over a network, many historic notions about the nature of
      publications and libraries will be called into question. The authors review the
      history of copyright law and some basic concepts of copyright, particularly
      "first sale" and "fair use." They also discuss the effects past technological
      changes have had on the law and on the often-competing concerns of authors,
      publishers, and readers/users. Finally, they discuss the implications for medical
      schools of digital publications, digital libraries, and the proposed changes to
      copyright law.

PMID- 8540965
TI  - Why does moral reasoning plateau during medical school?

PMID- 8540966
TI  - Financing academic medical centers: a shared responsibility.

PMID- 8540967
TI  - Content analysis of research in undergraduate medical education.
AB  - The authors describe research in undergraduate medical education as reported in
      journal articles. A sample of 773 articles was randomly selected from 3,689
      articles published from 1975 through 1994. Content analysis was used to
      quantitatively assess subject interests and methods over the past 20 years. The
      most frequent topics related to curriculum, teaching, and student assessment.
      Over 45% (353) of the sample articles were reports of research activity (i.e.,
      they used specific methods to ascertain new facts, concepts, or ideas). The
      research reported was overwhelmingly conducted in a naturalistic environment; was
      evaluative or comparative in design; used observation, testing, or questionnaires
      to collect data; and included inferential statistical analyses. The research
      described by the authors confirms the close relationship between medical
      education and clinical or laboratory environments. The literature on
      undergraduate medical education reflects a lack of theory-based research and
      little evidence of work built on prior research, which may be partially due to
      the scattered nature of the literature. The increased numbers of authors per
      article over the study period may be indicative of increased interdisciplinary
      collaboration. The lack of reported external funding may be a problem of
      underreporting or it may be related to the large number of single-institution
      based studies.

PMID- 8540969
TI  - The machine in the garden.

PMID- 8540968
TI  - The state of the literature on primary care specialty choice: where do we go from
      here?
AB  - A large body of research on medical students' choice of primary care specialties
      has been published. However, the literature is difficult to interpret because of
      multiple biases, design weaknesses, small numbers of subjects, inconsistencies in
      both dependent and independent variables, and conflicting results. These
      weaknesses have been noted by authors who have reviewed the work in this area,
      but the authors have given little direction for ways to improve and build upon
      the current state of the literature. This paper provides a quantitative
      description of the content of the specialty choice literature. As part of a
      larger project that included an exhaustive literature analysis, all research on
      primary care specialty choice published between 1987 and 1993 was collected and
      summarized according to study questions, designs, data sources, samples, theory,
      and outcome variables. Portions of this information were used to rate the quality
      of each study, yielding a score from zero to 100 that indicated the
      trustworthiness of the study's conclusions. Overall, the studies examined were
      found to use predominantly cross-sectional designs and to lack theoretical basis.
      Special curricular tracks, student personality, and self-reported influences were
      the most frequently studied determinants of primary care specialty choices. The
      results confirm previous qualitative descriptions of the state of the literature
      on specialty choice, and lead to recommendations for approaches to improve the
      quality of further work in this area. The research agenda that emerged from the
      larger project is also presented.

PMID- 8540970
TI  - Single-case experimental designs in medical education: an innovative research
      method.
AB  - This paper presents an argument for more extensive use of single-case
      experimental research designs in medical education research. Single-case
      experimental designs consist of a group of experimental techniques that are
      widely used in the social sciences but are just beginning to be utilized by
      medical researchers. The method emphasizes reliable observations of behavior,
      repeated measurements of outcome, and individualized tailoring of objectives for
      each subject; all of these occur within a system that allows an experimental
      analysis to be conducted. Single-case designs are particularly useful when only
      small numbers of participants are available for a relatively long period of time.
      Trends in medical education toward individualized instruction, adult-centered
      learning, and fine-grained analyses of medical skills and knowledge make this
      field especially amenable to single-case experimental designs. Issues of internal
      and external validity, generality, practicality, and ethics are discussed, and
      several typical designs are illustrated. While the emergence of qualitative
      research methods in medical education may prove useful, single-case designs can
      maintain experimental science's emphasis on methodologic rigor, while allowing
      the flexibility often needed to conduct research in applied settings.

PMID- 8540971
TI  - When pharmaceutical manufacturers' employees present grand rounds, what do
      residents remember?
AB  - PURPOSE: To evaluate the educational effect on residents of a grand rounds given
      by a pharmaceutical company employee. METHOD: Using a retrospective cohort study
      design, the authors questioned 75 housestaff at a university hospital three
      months after a February 1990 grand rounds on Lyme disease to determine whether
      the residents' beliefs about the drug of choice for this disease differed between
      attendees and non-attendees. Odds ratios, 95% confidence intervals, and logistic
      regression were used for the analysis of results. RESULTS: The 22 housestaff who
      had attended the grand rounds were more likely to choose appropriately the
      cephalosporin manufactured by the speaker's company over other drugs for patients
      with Lyme disease presenting with second-degree heart block (adjusted odds ratio
      of 8.4; 95% CI 2.1-38.9). However, they also chose it inappropriately for first
      degree heart block (adjusted odds ratio of 7.8; 95% CI 1.6-45.5). None of the
      attendees, compared with 11 (21%) of the non-attendees, named an oral antibiotic
      for both of two milder presentations, even though oral therapy would be more
      appropriate (p = .027). CONCLUSION: The results suggest that grand rounds
      effectively change residents' beliefs, but a sponsoring company's drug may be
      favored. Information assimilated in this way may not be well supported by the
      scientific literature and could result in a choice of treatment that is more
      expensive than other acceptable treatments.

PMID- 8540972
TI  - Medical school policies for part-time faculty committed to full professional
      effort.
AB  - The need for information about medical schools' efforts to allow faculty who wish
      to remain fully academic but work less than full time has been growing steadily.
      Building on the AAMC's 1993-94 survey of faculty appointment and tenure policies,
      in 1994 the authors surveyed 102 U.S. and Canadian medical schools that had
      answered yes to the question, "Does the medical school provide for faculty who
      choose to work less than full-time but whose full professional effort is directed
      towards the institution?" Seventy-one U.S. and Canadian medical schools reported
      provisions for "full professional effort" (FPE) faculty, and 32 of these had
      developed specific procedures for such faculty. Other nomenclatures in use for
      FPE faculty include "limited full-time," "full status/partial load," and "reduced
      period of responsibility." Almost half of the 71 survey respondents reported that
      FPE faculty could be appointed to, or remain on, a tenure track; more than half
      of these schools said that they lengthened the probationary period on a prorated
      basis. Women, much more frequently than men, had chosen the FPE option,
      especially women clinical faculty. While FPE faculty face more challenges than
      full-time faculty in accomplishing the tasks necessary for promotion in academic
      medicine, well-structured FPE options can benefit not only individual faculty
      members and their families but also the institution, which retains the commitment
      of valued faculty members seeking flexibility.

PMID- 8540973
TI  - Hydrofluoric acid burns: a review.
AB  - Hydrofluoric acid (HF) is a highly dangerous substance with a wide range of
      industrial as well as domestic applications. It is unique in both the severity of
      the cutaneous burns it may produce, and its potential for systemic and
      occasionally lethal toxicity. The literature on the treatment of HF injuries is
      extensive, though occasionally confusing and often contradictory, with no
      coherent management policy emerging. In this paper we present a comprehensive
      account of the evolution of therapy, drawing on clinical reports and experimental
      studies.

PMID- 8540974
TI  - An algorithmic approach to the treatment of hydrofluoric acid burns.
AB  - Hydrofluoric acid (HF) injuries have a potential for both systemic toxicity as
      well as severe tissue destruction. We present an algorithm for the management of
      HF burns. This algorithm addresses these issues emphasizing the differences
      between major and minor cutaneous burns, and includes the approach to inhalation,
      ingestion and eye injuries. Although algorithms can never be complete, we hope
      this algorithm will be used as an aid in the clinical management of these
      patients.

PMID- 8540975
TI  - Effects of washing acid injuries to the skin with water: an experimental study
      using rats.
AB  - A skin acid injury model has been constructed using SD rats and 1N HCl. The
      changes over time, with particular attention to subcutaneous tissue pH, were
      recorded and included a comparative study of the effect of washing with water at
      1, 3 and 10 min after injury, on subcutaneous tissue pH. After inflicting an acid
      injury, the subcutaneous tissue pH of control animals reached its minimum value
      at the seventh minute, and had not recovered to the pre-experimental level by the
      60th minute. In the group of rats which was washed at 1 min, the pH did not drop
      below 7.5, it remained virtually unchanged. In the group washed at 3 min, the pH
      declined slightly, but subsequent to washing, the pH increased gradually. In the
      group washed at 10 min, the changes in pH were almost the same as those in the
      untreated group. These results indicated that if washing was carried out before
      the subcutaneous tissue pH level reached a minimum value, any remaining acid on
      the skin surface could be washed away, effectively suppressing the subsequent
      fall in pH.

PMID- 8540976
TI  - Human keratinocyte culture using porcine pituitary extract in serum-free medium.
AB  - Extensive burn wound coverage remains a major problem in acute and reconstructive
      stages due to shortage of autologous skin donor sites. Many reports have
      described successful coverage of extensive burn wounds by using cultured
      keratinocytes sheet graft alone or overlaying a glycosaminoglycan substrate,
      allodermis or xenodermis. In our experience, the use of Boyce and Ham's serum
      free medium made the preparation of keratinocyte cultures simple and the cell
      growth was prompt. In this study, one of the supplements in Boyce's culture
      medium, the bovine pituitary extract (BPE at concentration of 140 micrograms/ml),
      was replaced by different concentrations of fresh frozen porcine pituitary
      extract (PPE). The protein concentration of the original preparation of PPE was
      also 140 micrograms/ml but in which 375 +/- 21 pg/ml (1/10 dilution) of platelet
      derived growth factor (PDGF) was detected by immunoassay (PDGF ELISA). Our
      results proved that PPE is an ideal supplement for the in vitro growth of
      keratinocytes, and when its protein concentration is 350 micrograms/ml will
      induce a significant keratinocyte growth by day 9 when compared to the regular
      BPE and also to the other concentrations of PPE (P < 0.05).

PMID- 8540977
TI  - Relations between copper, zinc and selenium intakes and malondialdehyde excretion
      after major burns.
AB  - Copper, zinc and selenium are involved in free radical scavenging. As trace
      element status is altered after major burns, related free radical scavenging may
      be decreased: consequently lipid peroxidation, reflected by increased urinary
      malondialdehyde excretion (MDA), is considerably increased. This preliminary
      study aimed to investigate the relationship between trace elements and MDA
      excretion. Sixteen patients aged 34 +/- 9 years (mean +/- s.d.) burned over 37 +/
      11 per cent of body surface, were studied prospectively. Trace element balance
      studies from days 1 to 7 and serum and urine concentrations on days 10, 15, 20
      and 25 were measured. The first 11 patients (groups 1--SBU < 80, and 2--SBU > or
      = 80) were given standard supplements and the five next patients increased
      supplements (group 3, SBU > or = 80). The MDA excretion from days 1 to 3 was
      correlated with burn severity (r = 0.59). The correlations between serum trace
      element levels after day 3 and MDA were negative: Cu, r = -0.065; Zn, r = -0.52;
      Se, r = -0.53. In Group 3, MDA excretion after day 3 decreased with increasing
      cumulative Zn (r = -0.46) and Se intakes (r = -0.57). It can be concluded that
      the MDA decrease after day 3 was not clearly attributable to the trace element
      supplements, but the negative trend observed between Zn and Se supplements and
      decreased MDA excretion requires further studies.

PMID- 8540978
TI  - Audit of intensive care burn patients: 1982-92.
AB  - This study attempts to measure and quantify changes in workload and outcome in
      clinically ill burn patients admitted to the intensive care unit at this
      institution over the 11-year period 1982-92. The case notes were studied for all
      patients admitted to the intensive care unit, 163 cases in total, but information
      was incomplete in 14. Mortality over the period is compared, using Chi squared
      analysis with Yates correction, with mortality probability from Bull's chart
      relating age and body surface area of burn (1971). The trends show increasing
      admission rates and referral rates to ICU from other hospitals in the region,
      despite declining admission rates to the regional burn unit as a whole. The
      duration of stay for admitted patients also shows an increase, the combination of
      these factors suggesting an increasing workload. There has been no change in
      outcome over the period. The figures provide a baseline for comparison of outcome
      in critically ill burn patients and are an important means by which to measure
      future change.

PMID- 8540979
TI  - Burn variables influencing survival: a study of 144 patients.
AB  - This review assess the influence of burn variables on patients' survival using
      epidemiological analysis of 144 patients admitted over a 2-year period, the
      overall mortality rate was 9.7 per cent. The risk of mortality in patients with
      30-50 and 50-80 per cent total body surface area (TBSA) burns was 16 and 86 times
      that in patients with less than 30 per cent TBSA burns respectively. The risk of
      mortality was multiplied by five when burns were full skin thickness or arrival
      was delayed for between 2 and 5 h. The increases in burn size, burn depth and
      arrival delay significantly raised the mortality rate (P < 0.0001, P = 0.02 and P
      = 0.01 respectively). When burn surface area (BSA) exceeded 30 per cent TBSA, the
      effect of the other two variables on survival were reinforced. When the patients'
      age was under 6 years and BSA was above 85 per cent TBSA, the risk of mortality
      was increased five times but insignificantly raised its rate.

PMID- 8540980
TI  - Influence of a changed care environment on bacterial colonization of burn wounds.
AB  - This study investigated the influence of a conditioned care environment per se on
      bacterial colonization of burn wounds. Two cohorts of burn patients were treated
      in the successive years 1992 and 1993, the first group in a (permanent) purpose
      designed unit and the second in wards of traditional 'open' design, during
      renovation of the unit. Patients who were admitted to the permanent and temporary
      units numbered 224 and 231 respectively, the groups being similar in features
      that generally influence the course and outcome of burn injuries. The principles
      and practice of treatment by the burn care team remained the same in both years.
      No significant difference in wound colonization rates was found between the two
      groups. We conclude that while the other known advantages of managing burn
      patients in purpose-designed units remain valid, a conditioned care environment
      per se does not influence bacterial colonization rates of burn wounds.

PMID- 8540981
TI  - Outcome of amputations in patients with major burns.
AB  - There is little mention in the literature of the outcome of patients who require
      amputations for large surface area burns. To determine their outcome, we devised
      a case-control study. Fifteen patients who underwent amputations between 1984 and
      1993 at the University of Louisville Burn Unit were analysed and compared to a
      similarly injured control group. Both groups represented severely burned patients
      with high total body surface areas involvement. Apache II scores, and per cent of
      inhalation injuries. The results showed a 60 per cent survival rate in each
      group. Unlike previous reports on electrical burns, the amputations in this
      series of primarily thermal injuries (12 of 15 patients) were performed late in
      the hospital course (mean, 15 days) and after previous attempts at limb salvage
      (mean, two procedures). By eliminating either non-viable or infected tissue,
      amputations served a role in obtaining a respectable survival rate for these
      severely injured patients that also compared favourably with the control group.

PMID- 8540982
TI  - Electrical injuries--morbidity, outcome and treatment rationale.
AB  - Electrical injuries are unique with respect to low mortality rates, but very high
      rates of short- and long-term morbidity, and overall outcome. Controversy still
      exists regarding the advantages of one-stage debridement versus early serial
      debridement of necrotic tissue. The purpose of this study was a retrospective
      evaluation of treatment, morbidity and outcome in a group of patients with
      electrical injuries. Over a 13-year period 1992 patients were admitted with acute
      burns to our burn centre. Electrical injuries occurred in 129 (6.5 per cent) of
      these patients. There were 38 high-tension injuries and 91 low-tension injuries.
      The average age was 33.7 years (5 months to 63 years), with burn wounds ranging
      from 1 to 57 per cent total body surface area (mean 9.5 per cent). Ninety-four
      (72.9 per cent) of these injuries were work related, and most occurred in males
      (85 per cent). A total of 323 surgical procedures were performed on those 129
      patients. An average of 0.48, surgical debridements per patient was necessary in
      the low-tension injury group and only three partial finger or toe amputations
      were necessary. In the high-tension group, 27 major limb amputations were
      performed after 2.3 debridements per patient, resulting in an overall major limb
      amputation rate of 35 per cent. The average length of stay was 22 days, and the
      cost of hospitalization ranged from $900 to $120 000 (mean !4,901). Significant
      long-term neurological deficits persisted in 73 per cent of patients at long-term
      follow-up (mean 4.5 years). Only 5.3 per cent of patients after high-voltage
      electrical injury were able to return to their premorbid job.

PMID- 8540983
TI  - Epidemiological data on burn injuries in Angola: a retrospective study of 7230
      patients.
AB  - This study describes the work carried out at the Burn Unit of the Neves Bendinha
      Hospital, Luanuda, Angola, during the 3-year period July 1991 to June 1994.
      During this period we admitted 2569 burned patients to our burn unit, and 4661
      were treated on an outpatient basis. The data from the patients were analysed to
      indicate the distribution according to age, sex, TBSA, cause of the lesion and
      mortality. Our study gives some epidemiological data on burns in an undeveloped
      country undergoing a war, outlining the specific problems compared to the reality
      in civilized countries.

PMID- 8540984
TI  - Petrol--something nasty in the woodshed? A review of gasoline-related burns in a
      British burns unit.
AB  - Petrol (gasoline) is probably the fuel most easily available and widely in use
      today. Indeed, most households have a can lurking in the garden shed or basement
      for domestic use. It's chemical properties make it a highly explosive as well as
      a combustible fluid, a fact that is sometimes poorly appreciated. We looked at
      the incidence of petrol-related burns seen in our unit over a 2-year period.
      Nearly 33 per cent of the adult male admissions were petrol-related and 16 per
      cent were in children under the age of 16 years. The commonest cause of injury
      was attempting to start or accelerate a bonfire (38 per cent) with only a small
      number of barbecue injuries (4 per cent). Petrol causes a significant number of
      burn injuries a year, and particularly worrying were the number of children
      injured. However, we feel there is a need for greater public education and
      perhaps stricter control of this substance.

PMID- 8540985
TI  - Burns induced by plants.
AB  - Plants of the family Umbelliferae are known to cause a phytophotodermatitis due
      to a phototoxic reaction caused by furocoumarin (psoralens) and simultaneous
      exposure to sunlight. We report four patients with partial skin thickness burns,
      induced by this phototoxic reaction. One occurred after contact with parsley
      (Apium petroselinum) and three others after contact with giant hogweed (Heracleum
      mantegazzianum) and simultaneous exposure to sunlight.

PMID- 8540986
TI  - Procel burn cover used as a total body dressing in burns.
AB  - A 26-month-old boy sustained a scald injury covering 83 per cent of his total
      body surface area (TBSA). He also developed sepsis and multiorgan failure (MOF).
      Locally he was treated with Procel burn cover and silver sulphadiazine cream
      (SSD) for 23 days. By using Procel, the dressing-change time was shortened
      significantly. Procel burn cover controlled core and skin temperature more
      effectively compared to conventional dressing, and the staff acceptance increased
      because of its easy and fast use. Based on our observation, this material can be
      used successfully as a total body dressing with children with extensive partial
      thickness burns or temporarily in full thickness burns until wound excision can
      be performed.

PMID- 8540987
TI  - Deep burns following epileptic seizures.
AB  - Epileptic seizure is a risk factor for deep burns. We report five seizure-related
      thermal injuries. All burns occurred in the home while the patients were
      performing everyday domestic tasks. Many burns resulting from epilepsy are
      avoidable.

PMID- 8540988
TI  - Thermal burns with injury to the intestine in a congenital hernia sac.
AB  - It is unusual to have a bowel injury in association with thermal injury. It is
      even rarer to encounter a patient with cerebral palsy and thermal injury to an
      intestinal loop in a congenital hernia sac. A case report of such a child is
      presented and the management is discussed.

PMID- 8540989
TI  - Intraosseous infusion--a technique available for intravascular administration of
      drugs and fluids in the child with burns.
AB  - Intraosseous infusion is a potential route for intravenous access in the child
      with burns who required vascular access that cannot be achieved in a timely
      manner via another route. Drugs, fluid and blood can be given via this route and
      marrow aspirate drawn for laboratory analysis. It is a reliable, safe procedure
      with a low incidence of complications.

PMID- 8540990
TI  - Recent references.

PMID- 8540991
TI  - Skin banks from living donors.

PMID- 8540992
TI  - Seromas in the breast: imaging findings.
AB  - Breast seromas are tumor-like collections of serosanguineous fluid in breast
      tissue that occur following excisional biopsy, lumpectomy, mastectomy, and
      plastic surgery procedures such as augmentation, prosthesis explantation, breast
      reduction, and breast reconstruction. Mammographically seromas are water-density
      masses located at the surgical site. They exhibit features characteristic of
      fluid collections on sonographic evaluation. This article reviews the spectrum of
      imaging findings associated with breast seromas.

PMID- 8540993
TI  - [Childhood diarrhea in rural Nicaragua: beliefs and traditional health
      practices].
AB  - In Nicaragua, the principal cause of infant mortality is diarrhea, which is
      responsible for 40% of these deaths annually. This statistic reflects the low
      usage of health services and oral rehydration therapy (ORT). In an effort to
      improve the situation, several studies were carried out in Villa Carlos Fonseca
      municipio. This report describes two of those studies, one ethnographic and the
      other epidemiologic (conducted in 1989 and 1990, respectively), to find out
      beliefs and traditional health practices and their influence on the way in which
      mothers responded to their children's diarrheal illness. The ethnographic study
      involved interviewing 70 mothers with an average age of 28 years who had children
      under 2 years of age. The children represented two groups: one at high risk for
      diarrhea and the other at low risk. The objectives were to learn the traditional
      names for diarrhea, the perception of risk, and the treatments that were used.
      The epidemiologic study included 391 mothers over 14 years of age with one or
      more children under age 5 years, of whom 215 had had diarrhea in the two weeks
      preceding the survey. The objectives were to describe local beliefs and health
      practices and to determine the incidence of diarrheas according to the diagnosis
      made by the mothers. At least 12 types of diarrhea were identified, for which
      terms such as "empacho" and "sol de vista" were used. In most cases, the mothers
      had more confidence in folkloric treatments that they themselves or the
      traditional healers (curanderos) applied than in the services offered at health
      centers. This attitude limited their use of health services and ORT, although it
      was observed that in certain cases traditional treatments were used in
      combination with those of western medicine. There was a direct but nonsignificant
      correlation between the level of schooling of the mothers and the frequency with
      which they visited the health center. The authors suggest the effects of
      massages, herbal baths, and other traditional treatments should be studied to
      evaluate their effectiveness and adapt them, to the extent possible, to "modern"
      medicine. Health services providers should become familiar with traditional
      nomenclature and beliefs in order to be able to communicate better with mothers
      and steer them away from harmful practices toward improved results in infant
      diarrheal disease prevention programs.

PMID- 8540994
TI  - [The evaluation of a monoclonal antibody panel for Lyssavirus typing in Mexico].
AB  - The purpose of this study was to evaluate the ability of a panel of eight
      antinucleocapsid monoclonal antibodies developed in Europe to identify different
      strains of rabies virus isolated from a variety of animal species from diverse
      geographic areas in Mexico. Fifty-one virus-positive samples of brain tissue from
      various animal species and humans were studied. Material from these samples was
      used to infect mice, whose brains were later tested by indirect
      immunofluorescence, using the monoclonal antibodies described above. Strains of
      the virus that showed antigenic variations were sent to the Pasteur Institute in
      Paris for confirmation of the results. No mouse brain sample showed a pattern of
      antigenic reactivity that indicated the presence of a Lyssavirus other than the
      classic rabies virus. However, four antigenic variations from serotype 1 of
      classic rabies were found. The panel of antibodies was judged to be useful for
      the rapid classification of rabies virus in Mexico. It is possible that
      autochthonous antigenic variations are appearing among strains circulating in
      that country, a scenario that could explain some of the failures observed with
      certain vaccines. For this reason, there is a need to produce antinucleocapsid
      monoclonal antibodies with strains of rabies virus indigenous to the area.

PMID- 8540995
TI  - [The trends by province of tuberculosis in Cuba: 1979-1993].
AB  - This study was carried out in order to describe tuberculosis trends in Cuba and
      its provinces between 1979 and 1993. For this purpose, reports of new cases of
      all forms of tuberculosis were obtained from the National Statistics Bureau of
      the Ministry of Public Health. In addition, tuberculosis incidence rates and
      their trends between 1979 and 1992 were determined. The data were analyzed by
      means of simple linear and exponential regression models. Finally, the percentage
      reductions in incidence between 1979 and 1992 were calculated and the observed
      changes were described in reference to the expected values derived from the
      regression models. The number of new tuberculosis cases reported in Cuba
      decreased from 1133 (11.6 per 100,000 population) in 1979 to 633 (5.8 per
      100,000) in 1992 (a 44% reduction). In 1993, 788 cases were reported (7.2 per
      100,000). In almost all the provinces the incidence tended to decrease between
      1979 and 1992, and the average annual number of new case notifications fell
      between 4.0 and 5.4%, although in some, less than 3%. In 1992, the number of new
      case notifications in the country was 25% higher than in 1991, and the incidence
      rates in all the provinces were higher than expected. The incidence in La Habana,
      the City of Havana, Villa Clara, Cienfuegos, Ciego de Avila, Santiago de Cuba,
      and Guantanamo exceeded the overall national incidence. In 1993, incidence in the
      country was 55.6% higher than it had been in 1991 and 24.5% higher than in 1992.
      Incidence rose in all provinces, and especially in the City of Havana, Matanzas,
      and Guantanamo. Although incidence remained below 8 cases per 100,000 population
      between 1992 and 1993, it rose during those years, as it did in other countries.
      The increase appears to be attributable to the economic crisis that affects the
      country and to have very little connection to human immunodeficiency virus
      infection.

PMID- 8540996
TI  - [Mercury in the hair of pregnant and lactating Chilean mothers].
AB  - Mercury-containing industrial waste has been released into the coastal waters of
      the Eighth Region of Chile for around two decades. This study, carried out from
      1991 to 1993, sought to measure mercury concentrations in the hair of pregnant
      and lactating women from villages near the coast and in the interior of the
      region in order to examine the relationship between the concentration of mercury
      and seafood consumption. The survey questionnaire used in 1991 to determine
      seafood consumption did not ask about the frequency of consumption of fish,
      shellfish, and algae but only whether the women who were pregnant or breast
      feeding consumed a minimum of one fish-based meal per week. The questionnaire
      used in 1992 and 1993 asked about the daily and weekly consumption of seafood in
      general (fish, shellfish, and algae). Spectrophotometry was used to determine the
      total mercury concentration in samples of 100 mg of hair from 153 pregnant and
      lactating women in 11 fishing villages of the Eighth Region where seafood is
      regularly consumed. None of the women had occupational exposure to mercury. Total
      mercury concentration was also determined in hair samples from a control group
      composed of 26 pregnant and lactating women from Pinto and El Carmen, villages in
      the interior of the same region where seafood was rarely eaten. The arithmetic
      mean of the total mercury concentration in hair was 1.81 mg/kg of body weight for
      the study group (standard deviation [SD] 1.52) and 0.42 mg/kg for the control
      group (SD 0.15)--a statistically significant difference (P < 0.01). Pairwise
      comparisons also revealed statistically significant differences (P < 0.05)
      between the mean for the interior group and the means for the women in the nine
      villages closest to the sources of the pollution, but not between the mean for
      the interior group and those for women in the two villages at the extreme north
      and south of the study zone, who lived farthest from the contaminated waters. The
      total mercury concentration in hair was significantly higher in women who
      indicated that they ate fish seven or more times per week; in those who said they
      ate fish, shellfish, or algae five or more times per week; and in those who had
      lived 20 or more years in their village. No statistically significant differences
      were found when the results were analyzed by age.

PMID- 8540997
TI  - [The protective efficacy of BCG against leprosy in Sao Paulo, Brazil].
AB  - The protection against leprosy conferred by BCG vaccination was evaluated in a
      case-control study. Selected for the study were 97 patients under 16 years of age
      who had been diagnosed with leprosy (cases) and 385 healthy persons (controls),
      who were matched according to sex, age, place of residence, and type of contact
      (intra- or extradomicilliary). The cases were selected from a register of active
      cases as well as a series of new leprosy patients treated in 50 centers in the
      city of Sao Paulo, Brasil. To estimate the protective effect of BCG, the
      prevalences of BCG scars among cases and controls were compared. The presence of
      one or more scars was associated with a protective efficacy of 90% (95%
      confidence interval: 78%-96%). Stratified analysis by age group, sex,
      socioeconomic level, and clinical form of leprosy did not reveal any important
      differences in the protection conferred by the vaccine. The significance of these
      findings and the appropriateness of using BCG in leprosy control programs is
      discussed.

PMID- 8540998
TI  - [The rabies situation in Latin America from 1990 to 1994].

PMID- 8540999
TI  - Logarithmic growth in surface adsorption.
AB  - A review is made of experimental data on surface adsorption of particles and
      polymers from water solutions, their analysis and interpretation in terms of
      general theoretical models of surface adsorption. A characteristic isotherm and
      kinetics is found and defined as logistic growth. The discussion is focused on
      literature indicating a possibility of describing logistic growth by using
      statistical (probabilistic) models based on the mean stay time of molecules on
      the surface. The statistical approach is further elaborated as follows: ligands
      arriving at a surface have a binary choice-to bind or to become reflected. Since
      the number of attempts to bind, n, will be high we can use the true mean of the
      binomial distribution to describe the reaction and write: S = n a; where S is the
      number of successful attempts and a is the probability of binding. The
      probability, a, will depend on the site density and on the sticking probability
      of the ligand at the binding site. Several experimental studies show that surface
      reactions have a nonlinear time- and concentration dependence and can be
      described by a Boltzmann factor of the form, I(1-e-t/tau); where I is the flux of
      ligands to the surface and tau = stay-time. The exponential form indicates that
      the reactions are self-dependent, and a statistical model for description of such
      reactions will be of the form: S(t) = N(o)(1-2-alpha t) (2-beta t); where N(o) is
      the number of molecules present in the system, alpha relates to the probability
      of positive cooperativity or t-dependent binding, and beta relates to the
      probability of desorption.

PMID- 8541000
TI  - Genetic polymorphism of the alpha 2-adrenergic receptor is associated with
      increased platelet aggregation, baroreceptor sensitivity, and salt excretion in
      normotensive humans.
AB  - It is likely that a number of independent heritable traits, each encoded by a
      singular gene, contribute to pathologic elevations in blood pressure in humans.
      Genetic polymorphisms of individual genes may result in intermediate phenotypes
      which, by themselves, do not raise blood pressure, but, coupled with
      environmental or epistatic forces, contribute to the prevalence of human
      hypertension. The gene for the alpha 2-adrenergic receptor encoded by chromosome
      10 (C10 A2AR) is polymorphic, and Southern blotting with a cDNA probe following
      restriction enzyme digest of this gene results in fragments of either 6.3 kb or
      6.7 kb in size. We reported an association between homozygosity for the 6.3 kb
      allele and hypertension in blacks. Blacks with hypertension also have an
      increased risk for thrombotic stroke, increased baroreceptor sensitivity, and
      decreased sodium excretion. We noted that the C10 A2AR, which modulates
      norepinephrine release in blood-pressure-regulating regions of the brain, is also
      expressed on platelets and in the kidney. We postulated that functional changes
      associated with the C10 A2AR gene polymorphism could be responsible for increased
      baroreceptor sensitivity, epinephrine-mediated platelet aggregation, and
      decreased sodium excretion in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541001
TI  - Metabolic derangements in nonmodulating hypertension.
AB  - A positive association exists between insulin resistance, dyslipidemia, and
      hypertension, specifically salt-sensitive hypertension. A subgroup of salt
      sensitive normal and high renin hypertensives called nonmodulators (NM) manifest
      an inability to modulate the adrenal and renal blood flow responses to a change
      in dietary sodium. Therefore, we tested the hypothesis that the NM subgroup would
      be insulin resistant and dyslipidemic when compared with normal and high renin
      hypertensives, in whom modulation is intact (M). Forty-six nondiabetic
      hypertensive individuals were evaluated and their modulation status defined by
      either renal or adrenal criteria. Fasting blood was drawn for measurement of
      several metabolic factors. Since the NM group had a greater body mass index (BMI)
      it was subdivided into a "lean" subgroup that matched the BMI of the M group. The
      fasting insulin levels in both the total NM and lean NM groups was significantly
      higher than in the M group (P = .013 and .04, respectively). There were no
      differences in age, blood pressure, or plasma/serum levels of glucose,
      triglycerides, total cholesterol, or potassium. NM had elevated fasting insulin
      levels compared to M, compatible with an insulin resistant state, but this
      insulin resistance are dissociable in the hypertensive population.

PMID- 8541002
TI  - Effect of low-dose ramipril on microalbuminuria in normotensive or mild
      hypertensive non-insulin-dependent diabetic patients. North-East Italy
      Microalbuminuria Study Group.
AB  - Microalbuminuria predicts early mortality and renal disease in non-insulin
      dependent diabetic patients. In insulin-dependent diabetic patients, angiotensin
      converting enzyme inhibition decreases microalbuminuria and retards the
      progression of renal disease. The aim of this study was to evaluate the effect of
      low dose ramipril on albumin excretion rate (AER) and blood pressure in non
      insulin-dependent diabetic patients with persistent microalbuminuria (AER > 20 <
      200 micrograms/min) and normal blood pressure or mild hypertension. The study was
      a randomized, double-blind, placebo-controlled clinical trial of 6 months
      duration at 14 hospital-based diabetes centers in northeastern Italy. Blood
      pressure, plasma glucose, and body weight were determined every month; AER, serum
      creatinine, glycosylated hemoglobin, and plasma lipids at baseline, after 1
      month, and at the end of the study. Of 122 non-insulin-dependent diabetic
      patients randomly allocated in blocks of four to receive either ramipril (1.25
      mg/day) or placebo, 108 (54 in the ramipril group and 54 in the placebo group)
      completed the study. At baseline, age, duration of diabetes, body mass index, and
      glycosylated hemoglobin were similar in the two groups and remained unchanged
      throughout the study. In the placebo group, AER rose from a baseline median of 65
      micrograms/min (range 53 to 76, 95% confidence Interval) to 72 micrograms/min (57
      to 87) and to 83 micrograms/min (62 to 104) after 1 and 6 months, respectively,
      but fell from 62 micrograms/min (48 to 76) to 45 micrograms/min (33 to 57) and to
      53 micrograms/min (38 to 69), respectively, in the ramipril group, a significant
      difference between the groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541003
TI  - Alterations of calcium metabolism and of parathyroid function in primary
      aldosteronism, and their reversal by spironolactone or by surgical removal of
      aldosterone-producing adenomas.
AB  - In order to investigate the possible existence of abnormal calcium metabolism and
      parathyroid function in primary aldosteronism (PA), we have compared the
      calcium/parathyroid hormone (PTH) profile of patients with PA with the profile of
      healthy normotensive subjects and of patients with essential hypertension (EH).
      Furthermore, we have evaluated the effects of spironolactone and the surgical
      removal of aldosterone-producing adenomas on the calcium/PTH profile in the PA
      patients. Four groups of 10 subjects each participated in the study: 1)
      hypertensive patients with PA, 2) patients with low-renin EH (LREH), 3) patients
      with normal-renin EH (NREH), 4) normotensive healthy subjects (NS). The four
      groups were well-matched for age, sex, body mass index, and renal function. The
      three hypertensive groups were also matched closely for blood pressure values and
      for duration of hypertension. In all subjects, after 1 week of a controlled
      intake of Na and K, the following parameters were measured: urine excretion of
      Na, K, Ca, Mg, and P, plasma levels of K, Mg, inorganic P, total calcium and
      ionized calcium, and plasma renin activity, aldosterone concentration, and intact
      PTH. Blood pressure and laboratory parameters were determined again in all the PA
      patients after 1 month of 100 mg daily spironolactone administration, and in four
      out of the 10 PA patients 2 months after surgical removal of aldosterone
      producing adenomas. All of these subjects had undergone the same controlled
      intake of Na and K indicated above. Serum intact PTH was higher in PA patients
      than in the other three groups (P < .01), and serum ionized calcium was
      significantly higher in normotensive subjects than in the three hypertensive
      groups (v PA P < .01, v LREH and v NREH P < .05). An increase in serum ionized
      calcium and a decrease in PTH level were associated with both spironolactone
      administration (P < .001) and surgical treatment (P < .05). These results suggest
      the presence of calcium metabolism alterations in both PA and EH patients, but
      that these alterations are more exaggerated in PA, so that higher PTH levels are
      needed for maintaining low-normal levels of serum ionized calcium.

PMID- 8541004
TI  - Vitamin D is related to blood pressure and other cardiovascular risk factors in
      middle-aged men.
AB  - A previous study has shown that serum levels of the active vitamin D metabolite
      1,25-(OH)2-vitamin D were inversely related to blood pressure levels while the
      prohormone 25-OH-vitamin D was found to be related to insulin metabolism. Also
      other clinical and experimental data support the view that vitamin D metabolism
      is involved in blood pressure regulation and other metabolic processes. The
      present study was conducted in order to see if the above mentioned relationships
      between the vitamin D endocrine system and blood pressure, as well as other
      cardiovascular risk factors, could be found in a cross-section population-based
      study. Serum levels of 1,25-(OH)2-vitamin D, 25-OH-vitamin D, and blood pressure
      were therefore measured in 34 middle-aged men and metabolic cardiovascular risk
      factors were evaluated by means of intravenous glucose and fat tolerance tests,
      euglycemic hyperinsulinemic clamp, lipoprotein measurements, and lipoprotein
      lipase activity determinations. Serum levels of 1,25-(OH)2-vitamin D were found
      to be inversely correlated to the blood pressure (r = -0.42, P < .02), VLDL
      triglycerides (r = -0.47, P < .005), and to triglyceride removal at the
      intravenous fat tolerance test (r = 0.34, P < .05), while serum levels of 25-OH
      vitamin D were correlated to fasting insulin (r = -0.35, P < .05), insulin
      sensitivity during clamp (r = 0.54, P < .001), and lipoprotein lipase activity
      both in adiposal tissue (r = 0.48, P < .005) and skeletal muscle (r = 0.38, P <
      .03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541005
TI  - Effect of amlodipine and felodipine on sympathetic activity and baroreflex
      function in normal humans.
AB  - Baroreflex sensitization and direct sympatholytic effects have been suggested as
      contributing mechanisms to the effects of dihydropyridine calcium channel
      blockers in hypertension and heart failure. In this study, we tested the
      hypothesis that either amlodipine or felodipine would decrease norepinephrine
      levels and enhance cardiac, peripheral vascular, or sympathetic responses to
      baroreflex perturbation in healthy humans. Six healthy male volunteers aged 21 to
      40 participated. Heart rate, forearm blood flow, arterial pressure, and
      norepinephrine kinetics were assessed in the supine position, after 15 min of 60
      degrees head-up tilt, after 15 min of 30 degrees head-down tilt, and after 15 min
      head-down tilt with phenylephrine infused to raise mean arterial pressure 10 to
      15 mm Hg. Studies were conducted double-blind on 3 different days 8 to 12 h after
      placebo, 5 mg amlodipine, and 10 mg felodipine. Resting heart rate, mean arterial
      pressure, forearm vascular resistance, plasma norepinephrine, and norepinephrine
      spillover were not affected by amlodipine or felodipine. During upright tilt,
      head-down tilt, and phenylephrine, each variable increased and decreased as
      expected after placebo. There was no effect of either amlodipine or felodipine on
      any response to any maneuver. Baseline sympathetic activity as reflected by
      plasma norepinephrine and norepinephrine spillover are not altered by either
      amlodipine or felodipine. Neither drug acutely sensitizes baroreflex function in
      normal humans over the degree of perturbation produced in these protocols.

PMID- 8541006
TI  - The effect of enalapril on mortal and morbid events in patients with hypertension
      and left ventricular dysfunction.
AB  - The objective of this study was to examine the effect of enalapril on morbid and
      mortal events in patients with left ventricular dysfunction and hypertension
      using a retrospective analysis of patients with systolic left ventricular
      dysfunction (ejection fraction < or = 0.35) who participated in the Studies of
      Left Ventricular Dysfunction (SOLVD). Among the 6797 patients who were randomized
      to enalapril or placebo, 2652 had history of hypertension, 1508 had systolic
      blood pressure (SBP) > or = 140 mm Hg, and 985 had diastolic blood pressure (DBP)
      > or = 90 mm Hg. During average follow-up of 40 months, the rate of
      hospitalization for congestive heart failure was lower in the enalapril group
      than the placebo group among patients with history of hypertension (20.6% v
      28.3%, P < .001, relative risk [RR] 0.664), and among those with elevated DBP
      (16.5% v 26.0%, P < .001, RR = 0.574), or SBP (19.5% v 27.7%, P < .001, RR =
      0.647) at baseline. These risk ratios were similar to those observed in patients
      without history of hypertension (RR = 0.647). Also, the decreased rates of
      mortality, myocardial infarction, stroke, and unstable angina observed in SOLVD
      were seen, with similar relative risks, in patients with (RR = 0.927, 0.836,
      0.979, 0.900, respectively) and without (RR = 0.866, 0.729, 0.775 and 0.743)
      history of hypertension as well in those with elevated SBP (RR = 0.841, 0.806,
      0.707, 0.867) or DBP (RR = 0.791, 0.889, 0.755, 0.872) at baseline.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8541007
TI  - Insulin induces medial hypertrophy of myocardial arterioles in rats.
AB  - To investigate the effect of hyperinsulinemia on arteriolar hypertrophy,
      myocardial hypertrophy, and blood pressure, we administered insulin
      intraperitoneally to SHR and WKY rats for 3 consecutive weeks. To prevent
      hypoglycemia, the drinking water contained 10% sugar, and to accentuate the blood
      pressure, their chow contained 8% table salt. Blood pressure was measured by the
      tail-cuff method. Heart weights were factored with body weights. Arterioles of
      approximately 100 microns in diameter were examined at the end of the experiment
      and the vascular wall thickness was factored with the lumen diameter. At the end
      of 3 weeks, blood pressure rose in the SHR but not in the WKY rats. The heart
      weights in the WKY normotensive rats did not increase, whereas in the SHR they
      did. Furthermore, there was a significant rise in vessel wall thickness in the
      rats that received insulin, whether there was a rise in blood pressure or not and
      whether they had an increase in heart weight or not. There was a similar rise in
      blood glucose in all the groups, with slightly more accentuated rise in the SHR
      that received insulin. Nevertheless the increase in vascular wall thickness
      occurred only in the groups which received insulin. This seems to preclude the
      importance of hyperglycemia per se as the causative agent for the increase in
      vascular wall thickness in this study. The increase was in the form of medial
      hypertrophy without any sign of atherosclerosis. It seems, therefore, that
      hyperinsulinemia is associated with hypertrophy of the media of arterioles
      regardless of the increase in heart weight or the rise in blood pressure.

PMID- 8541008
TI  - Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab
      directed against digoxin in DOCA-salt hypertensive rats.
AB  - Although volume and vasoconstriction have been considered polar elements in a
      useful pathogenetic hypertension model, many observations suggest that
      vasoconstriction is involved in volume-dependent hypertension, reflecting the
      effect of a digitalis-like factor. To examine that possibility, we assessed the
      depressor responses to Digibind, an antibody Fab directed against digoxin, in a
      volume-dependent model--DOCA-salt-induced hypertension in rats. Digibind (10
      mg/kg, intravenously) induced a gradual blood pressure fall over 2 h that was
      sustained for 4 h (P < .001). Blood pressure did not fall with Digibind when DOCA
      was administered without salt or a high-salt intake was provided without DOCA.
      The intracellular sodium content of the rat aorta, measured by atomic absorption
      spectroscopy after cold choline wash, was increased in the DOCA-high-salt rats
      (23.3 +/- 2.7 mEq/L) compared to control rats (12.1 +/- 0.8 mEq/L; P < .001).
      Aorta sodium content, in parallel with blood pressure, was not increased either
      by dietary salt supplementation without DOCA, or by DOCA with a low-salt diet.
      Sodium pump activity was measured as 86Rb uptake into vascular smooth muscle
      (VSM). Both ouabain-sensitive and ouabain-resistant 86Rb uptake were
      significantly higher in VSM from DOCA-high-salt animals (P < .01). Despite its
      effectiveness in reducing blood pressure in this model, Digibind influenced
      neither VSM sodium content nor 86Rb uptake. The results are consistent with a
      role for a circulating digitalis-like factor in this volume-dependent model, but
      events at the VSM level are complex.

PMID- 8541009
TI  - Cilazapril reverses endothelium-dependent vasodilator response to acetylcholine
      in mesenteric artery from spontaneously hypertensive rats.
AB  - This study was designed to evaluate the effect of chronic treatment with
      cilazapril on vascular reactivity of aorta and mesenteric artery from Wistar
      Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg),
      an angiotensin converting enzyme inhibitor, was injected intraperitoneally twice
      a day for 4 weeks. Results demonstrated that acetylcholine (ACh)-induced
      relaxation in aorta and mesenteric artery from SHR was significantly less than
      that from WKY, cilazapril-treated WKY, and SHR. The impairment of ACh-induced
      relaxation in SHR was significantly reversed after cilazapril treatment and there
      were no significant differences among WKY, cilazapril-treated WKY, and SHR.
      Meanwhile, both N omega-nitro-L-arginine (LNNA; 10(-4) mol/L) and methylene blue
      (MB; 10(-5) mol/L) completely blocked the vasodilator response to ACh in aorta
      but only partly inhibited in mesenteric artery from WKY, cilazapril-treated WKY,
      and SHR. These LNNA- and MB-resistant vasodilator responses to ACh in mesenteric
      artery were only slightly inhibited by TEA (10(-3) mol/L) but not by indomethacin
      (5 x 10(-6) mol/L). These findings suggest that there may be an unidentified
      endothelium-dependent relaxing factor(s) (EDRF), which exists in the endothelium
      and may participate in the modulation of blood pressure in SHR. Results further
      demonstrate that the antihypertensive effect of cilazapril may be partly mediated
      by the reversing function of endothelium to release EDRF and LNNA-resistant,
      unidentified relaxing factor(s).

PMID- 8541010
TI  - Effects of hypertrophy and heart failure on [Na+]i in pressure-overloaded guinea
      pig heart.
AB  - Intracellular free sodium levels ([Na+]i) were assessed with 23Na nuclear
      magnetic resonance (NMR) spectroscopy in isolated, Langendorff-perfused normal,
      compensated hypertrophied, and hypertrophied failing guinea pig hearts under
      several conditions. Baseline [Na+]i measured with a shift reagent was
      significantly greater than normal in the compensated hypertrophied hearts (12.8
      +/- 1.2 mmol/L v 6.4 +/- 0.7 mmol/L, means +/- SEM, P < .01), but not in the
      hypertrophied failing hearts (8.7 +/- 1.9 mmol/L, P = N.S.). Moreover, the
      highest levels of [Na+]i were seen just 3 to 4 weeks after aortic constriction.
      [Na+]i was inversely related to both time after aortic constriction (R = -0.71, P
      < .03) and to the degree of left ventricular hypertrophy (R = -0.79, P < .01),
      suggesting that the hypertrophied failing heart is capable of maintaining
      relatively normal [Na+]i. In addition, triple quantum filtered NMR measurements
      were made to assess changes in [Na+]i subsequent to altered perfusion or loading
      conditions. In hypertrophied failing hearts, but not normal hearts, low coronary
      perfusion pressure (60 cm H2O) was associated with relatively higher [Na+]i
      (ANOVA, P < .05), suggesting greater sensitivity of hypertrophied failing hearts
      to hypoperfusion. On the other hand, when all hearts were perfused at 90 cm H2O
      and intraventricular balloon volume was increased from 100 microL to 300 microL,
      [Na+]i increased significantly only in the normal guinea pig hearts (12.3 +/-
      1.8%, P < .01). These findings suggest complex changes in the expression or
      modulation of proteins involved in Na+ regulation. Interpretation regarding the
      physiological significance of these changes depends on the specific mechanism(s)
      proposed. Previous work in this and other models of hypertrophy suggest that
      changes in the number or activity of both Na(+)-K(+)-ATPase and Na(+)-Ca2+
      exchange proteins are involved.

PMID- 8541011
TI  - Short-term increase in prostaglandin I2 synthesis caused by cicletanine in
      patients with essential hypertension.
AB  - Cicletanine is a new antihypertensive drug that stimulates renal and vascular
      synthesis of prostaglandin (PG) I2 in experimental animals. However, there is
      little evidence that cicletanine increases the level of PGI2 in systemic blood of
      human subjects. To investigate the short-term antihypertensive mechanism of
      cicletanine, we measured serially the systemic blood pressure, the levels of 6
      keto-PGF1 alpha (a stable metabolite of PGI2) and PGE2, and renin activity in
      plasma after administration of the drug. Nine patients with essential
      hypertension on a diet without severe sodium restriction took 100 mg of the drug
      by mouth. Systemic blood pressure was measured hourly for 24 h before and after
      cicletanine administration. The two PGs of interest were extracted, purified by
      high pressure liquid chromatography, and measured by radioimmunoassay.
      Cicletanine decreased blood pressure 3 and 6 h after administration and increased
      the plasma level of 6-keto-PGF1 alpha. The increase in 6-keto-PGF1 alpha was
      small but significant (mean +/- SD, from 3.21 +/- 1.26 to 3.88 +/- 1.44 and later
      4.15 +/- 1.08 pg/mL by 3 and 6 h after administration; P < .05 and .01,
      respectively). The level of PGE2 had increased at 3 h after administration but
      returned to baseline by 6 h. Plasma renin activity was increased only at 24 h
      after administration. Cicletanine increased systemic PGI2 levels short-term,
      producing an antihypertensive effect in patients with essential hypertension.

PMID- 8541012
TI  - Glycogen synthase activity in two rat models of hypertension.
AB  - Several studies on both humans and animal models have reported a pathogenetic
      relationship among hyperinsulinism, insulin resistance, and hypertension. We have
      previously evaluated whole body glucose disposal and insulin sensitivity in
      different models of hypertensive rats, showing an increase rather than an
      impairment of glucose metabolism, which in turn was due to an improved ability of
      insulin to channel the absorbed glucose towards the nonoxidative disposal. Aiming
      to confirm our previous findings we performed the direct assay of skeletal muscle
      glycogen synthase on tissue samples from the previous clamp studies, as a rate
      limiting step enzyme of glycogen synthesis, under conditions of physiologic
      hyperinsulinemia and euglycemia. Glycogen synthase was assayed on samples from
      rectus muscle tissues of spontaneously hypertensive rats and high sodium, one
      kidney, one figure-8 hypertensive rats. Compared to controls, our data show an
      increased activity of glycogen synthase in the hypertensive animals, which is
      consistent with the increased glycogen synthesis previously reported. In
      conclusion, under our experimental conditions, hypertension and chronic
      hyperadrenergism are associated with an increased ability of insulin to stimulate
      glucose uptake and disposal. These latter effects are mainly due to an increase
      in nonoxidative disposal and glycogen synthase activity.

PMID- 8541013
TI  - Hypertensive urgency due to cholesterol embolization of kidneys.
AB  - Four weeks after left carotid endarterectomy, a 65-year-old man developed severe,
      acute hypertension due to cholesterol embolization of the kidneys. The diagnosis
      was established by the demonstration of mobile, protruding atheromata in the
      descending thoracic aorta and the visualization of distal embolization of a
      plaque fragment by transesophageal echocardiography.

PMID- 8541014
TI  - Simulation of diauxic production of cephalosporin C by Cephalosporium acremonium:
      lag model for fed-batch fermentation.
AB  - We extend a previously reported model (Chu, W.B.; Constantinides, A. Biotechnol.
      Bioeng. 1988, 32, 277-288) for the batch fermentation of cephalosporin C under
      the diauxic growth of Cephalosporium acremonium on glucose and sucrose to a fed
      batch system. For this purpose, a novel lag model is proposed for diauxie, which
      has two functional forms, each embodying the dependence of lag on total cell mass
      and secondary substrate concentration. This lag model is applicable for batch
      simulations for arbitrary initial glucose and sucrose concentrations. We used the
      previously reported batch data to perform locally optimized fed-batch
      simulations. When applied to fed-batch fermentations, multiple lag times were
      accounted for. These studies showed that fed-batch fermentations (under the
      restriction that cell mass concentration did not exceed 25 g/L) could be more
      productive than simple batch runs. A representative result for a glucose-pulse
      fed-batch run at optimal cephalosporin production is a productivity of 4.22 mg of
      cephalosporin C/(L.h) and a yield of 9.25 mg of cephalosporin C/g of total sugar
      used.

PMID- 8541015
TI  - Adsorption of copper and chromium by Aspergillus carbonarius.
AB  - Aspergillus carbonarius NRC 401121 adsorbs some copper and chromium from their
      solutions. The amount of the adsorbed metal per unit of biomass increased with a
      decrease in the biomass concentration. The increases in the initial
      concentrations of metals and pH of the solutions resulted in an increase in
      copper and chromium uptake. The optimum temperature for copper uptake was 25
      degrees C. Heating of the biomass prior to utilizing it in the adsorption tests
      decreased its metal adsorption capacity. Preincubation of the biomass with
      glucose enhanced the metal adsorption. The optimum glucose concentration in this
      process was 0.1%.

PMID- 8541016
TI  - Induction of cytochrome P-450IA1 activity in response to sublethal stresses in
      microcarrier-attached Hep G2 cells.
AB  - Cell damage for cells grown on microcarriers in suspension is a critical problem
      for scale-up of microcarrier reactors. In order to study cell damage as a
      mechanistic process, a cellular response that is more sensitive than changes in
      growth and death rates and would be more closely related to cell regulatory
      mechanisms would be advantageous. We have observed the induction of a specific
      cytochrome P-450 monooxygenase, P-450IA1 (CYP1A1), to be a sensitive method for
      assessing the response of microcarrier-attached Hep G2 cells to stress resulting
      from hydrodynamic shear and oxygen deprivation. The kinetics of induction and
      amount of CYP1A1 formed in response to subtle shear stress, moderate shear, and
      hypoxia are described. Increased stress results in increased CYP1A1 formation.

PMID- 8541017
TI  - An energetically structured model of mammalian cell metabolism. 1. Model
      development and application to steady-state hybridoma cell growth in continuous
      culture.
AB  - Incomplete understanding of mammalian cell culture kinetics hinders the ability
      of the biochemical engineer or biologist to design and control mammalian cell
      culture systems and to develop operating strategies. To address this problem, a
      mechanistic, structured mathematical model has been developed to simulate
      mammalian cell culture kinetics under a variety of bioreactor operating
      conditions. An important feature of in vitro mammalian cell metabolism in
      conventional cell culture media is the partial substitutability of the substrates
      glucose and glutamine for provision of energy in the cell. The utilization of
      glucose and glutamine by cells can therefore vary substantially, and these
      changes can profoundly affect the culture behavior. The model developed here
      specifically addresses the dynamics of substrate consumption and energy
      metabolism in mammalian cell culture. This energetically structured (ES) model is
      also distinguished by the consideration of changes in the specific cell mass with
      specific growth rate and the consideration of essential amino acids as
      potentially growth rate limiting. The model is applied here to simulate
      literature data on the growth and metabolism of a murine hybridoma in continuous
      culture.

PMID- 8541018
TI  - Growth enhancement of anchorage-dependent and anchorage-independent cells by
      coimmobilization of insulin with poly(allylamine) or gelatin.
AB  - An anchorage-dependent cell, mouse fibroblast STO cell and an anchorage
      independent cell, K562 cell, were cultured on a polymer membrane coimmobilized
      with insulin and adhesion factors, poly(allylamine), and gelatin. The former is
      cationic and electrostatically (non-biospecifically) enhances cell adhesion, and
      the latter is a hydrolyzate of collagen and biospecifically enhances cell
      adhesion. They were immobilized onto a surface-hydrolyzed poly(methyl
      methacrylate) membrane by water-soluble carbodiimide. The adhesion of both STO
      and K562 cells was accelerated by the immobilization of poly(allylamine) or
      gelatin. The insulin immobilization did not affect adhesion of either cell.
      Although the growth of STO cells was enhanced on the insulin-immobilized
      membrane, the growth of K562 cells was not. However, the coimmobilizaiton of
      insulin and a cell-adhesion factor accelerated growth of both cells. It was
      considered that an increased frequency of interaction between the immobilized
      insulin and the receptor led to the cell growth acceleration.

PMID- 8541019
TI  - Continuous fermentation and stripping of ethanol.
AB  - Recycling the contents of a continuous fermentor through a stripping column is
      proposed as a means of reducing product inhibition and lowering the cost of fuel
      ethanol production. A 2-L fermentor and 10-cm packed column were continuously
      operated for 150 days without contamination. Some fouling of the packing with
      attached yeast cells was observed which partially blocked the column. Cell yield
      was lower than in a simple continuous fermentor. Complete conversion of 200 g/L
      glucose feed and 90% conversion of 600 g/L glucose feed were achieved. Data were
      analyzed by computerized process simulation. Cost analysis indicated that, with
      heat recovery to reduce heating and cooling costs, the continuous
      fermentor/stripper is possibly a lower-cost alternative to conventional
      fermentation and distillation.

PMID- 8541020
TI  - Chemiluminescence-based inhibition kinetics of alkaline phosphatase in the
      development of a pesticide biosensor.
AB  - The use and application of the enzyme alkaline phosphatase in a chemiluminescence
      assay are discussed. The enzyme catalyzes the hydrolysis of a macrocyclic
      phosphate compound generating a chemiluminescence signal. On the basis of
      inhibition of this signal, a methodology for the detection and quantitation of
      organophosphorus-based pesticides has been developed. The methodology is studied
      with alkaline phosphatase in the bulk aqueous phase, and detection of the signal
      is accomplished by a simple optical setup. Parts per billion level detection of
      paraoxon and methyl parathion in bulk solutions is achieved. The technique is
      rapid and sensitive and is applicable to the detection of most organophosphorus
      based pesticides. The results from kinetic studies indicate a mixed type of
      inhibition of the enzyme by paraoxon and methyl parathion. The detection
      methodology forms an integral part of a biosensor under development and is
      adaptable to incorporating optical fibers for remote detection of pesticides.

PMID- 8541021
TI  - Enzymatic synthesis of peptides containing unnatural amino acids.
AB  - Several proteases were studied as potential catalysts for the enzymatic synthesis
      of oligopeptides containing the unnatural amino acid allylglycine, the overall
      objective being the synthesis of a reactive tetrapeptide that could be chemically
      polymerized into a potentially biocompatible or biodegradable material.
      Commercially available enzymes were screened for esterase activity toward the
      methyl ester of the amino acid allylglycine (DL-AgOMe) to identify potential
      catalysts for dipeptide synthesis. Proteases from Aspergillus oryzae and
      Aspergillus sojae, pronase E and protease Nagarse synthesized the protected
      dipeptide Cbz-allylglycine-phenylalaninamide (Cbz-L-Ag-L-PheNH2) from Cbz-DL
      AgOMe and L-PheNH2. However, the same enzymes were not able to catalyze the
      synthesis of Cbz-phenylalanine-allylglycine ethyl ester (Cbz-L-Phe-L-AgOEt).
      Thus, although these enzymes could use allylglycine as the acyl donor they could
      not employ it as the acyl acceptor in peptide synthesis. In contrast,
      chymotrypsin was able to use allylglycine ethyl ester (DL-AgOEt) as the acyl
      acceptor in the synthesis of Cbz-L-Phe-L-AgOEt, but was not able to synthesize
      Cbz-L-Ag-L-PheNH2. The two dipeptides, Cbz-allylglycine-phenylalanine and
      phenylalanine-allylglycine ethyl ester, served as substrates for the thermolysin
      catalyzed synthesis of the tetrapeptide Cbz-L-Ag-L-Phe-L-Phe-L-AgOEt.

PMID- 8541022
TI  - Expression and extensive characterization of a beta-glycosidase from the extreme
      thermoacidophilic archaeon Sulfolobus solfataricus in Escherichia coli:
      authenticity of the recombinant enzyme.
AB  - The gene coding for the beta-glycosidase from the archaeon Sulfolobus
      solfataricus has been overexpressed in Escherichia coli. The enzyme was purified
      to homogeneity with a rapid purification procedure employing a thermal
      precipitation as a crucial step. The final yield was 64% and the purification
      from the thermal precipitation was 5.4-fold. The expressed enzyme shows the same
      molecular mass, thermophilicity, thermal stability, and broad substrate
      specificity, with noticeable exocellobiase (glucan 1,4-beta-D-glucosidase)
      activity, of the enzyme purified from S. Solfataricus. We provide evidence that
      the beta-glycosidase can assume its functional state in E. coli without the
      contribution of N-epsilon-methylated lysine residues.

PMID- 8541023
TI  - Genes and behaviour.

PMID- 8541024
TI  - Apolipoproteins and gallstone disease.

PMID- 8541026
TI  - Is early detection of ovarian cancer possible?
AB  - Advances in medical technology have led to potentially useful techniques for the
      early detection of epithelial ovarian cancer. Early detection of ovarian cancer
      is crucial for survival as women found to have Stage I or II disease have a 5
      year survival of 90% and 70%, respectively, whereas those with advanced disease
      (Stage III and IV) have a survival of approximately 20%. The circulating tumour
      marker CA-125 has been extremely useful in following women known to have
      epithelial ovarian cancers. It has been employed in differentiating benign
      tumours from malignancies, and is now being tested in a variety of programmes for
      its role in the early detection of ovarian cancer. The application of endovaginal
      ultrasound and colour Doppler flow techniques to early detection of ovarian
      cancer have resulted in several large series identifying ovarian cancer in 1:1000
      to 1:2000 postmenopausal women screened. However, a high false positivity rate
      persists using CA-125 and ultrasound techniques alone or in sequence.
      Developments in molecular genetics may be extremely useful in evaluating women
      with inherited susceptibilities for this disease, but this probably represents
      only about 3% of the population of the women who develop epithelial ovarian
      cancer. The cost-benefit analysis of isolated screening for epithelial ovarian
      cancer using CA-125 and ultrasound techniques, even in women at high risk for the
      disease, would suggest that such screening is not cost-effective at this time.

PMID- 8541025
TI  - Artificial neural networks for decision support in clinical medicine.
AB  - Connectionist models such as neural networks are alternatives to linear,
      parametric statistical methods. Neural networks are computer-based pattern
      recognition methods with loose similarities with the nervous system. Individual
      variables of the network, usually called 'neurones', can receive inhibitory and
      excitatory inputs from other neurones. The networks can define relationships
      among input data that are not apparent when using other approaches, and they can
      use these relationships to improve accuracy. Thus, neural nets have substantial
      power to recognize patterns even in complex datasets. Neural network methodology
      has outperformed classical statistical methods in cases where the input variables
      are interrelated. Because clinical measurements usually derive from multiple
      interrelated systems it is evident that neural networks might be more accurate
      than classical methods in multivariate analysis of clinical data. This paper
      reviews the use of neural networks in medical decision support. A short
      introduction to the basics of neural networks is given, and some practical issues
      in applying the networks are highlighted. The current use of neural networks in
      image analysis, signal processing and laboratory medicine is reviewed. It is
      concluded that neural networks have an important role in image analysis and in
      signal processing. However, further studies are needed to determine the value of
      neural networks in the analysis of laboratory data.

PMID- 8541027
TI  - Molecular mechanisms of antiasthma therapy.
AB  - Recently there has been a much greater understanding of the molecular mechanisms
      involved in the actions of antiasthma therapy. beta 2-agonists are the most
      effective bronchodilators and act predominantly on airway smooth muscle. Recent
      evidence suggests that beta 2-receptors in airway smooth muscle are coupled
      directly to maxi-K channels and may thereby bronchodilate without an increase in
      cyclic AMP. The issue of beta-receptor tolerance has been reawakened by the
      recognition that the protective effects of beta 2-agonists against
      bronchoconstrictor stimuli may become tolerant. Inhaled glucocorticoids are the
      mainstay of treatment in patients with chronic asthma. They suppress asthmatic
      inflammation predominantly by reducing transcription of genes coding for
      inflammatory mediators (particularly cytokines) and enzymes (inducible NO
      synthase, inducible cyclo-oxygenase). The inhibition of gene transcription is
      mediated predominantly by inhibition of transcription factors, such as activator
      protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). There may be an
      abnormal activation of AP-1 in steroid-resistant asthma, and high concentrations
      of beta 2-agonists may induce a secondary resistance by an interaction between
      the transcription factor CREB and the glucocorticoid receptor. Theophylline may
      have immunomodulatory effects that are more important than its bronchodilator
      action. Some effects of theophylline are mediated via inhibition of
      phosphodiesterases and several PDE IV inhibitors are currently undergoing
      evaluation in asthma.

PMID- 8541028
TI  - Immunosuppressive and anti-inflammatory properties of interleukin 10.
AB  - Interleukin 10 (IL-10) indirectly prevents antigen-specific T-cell activation,
      which is associated with downregulation of the antigen presentation and accessory
      cell functions of monocytes, macrophages, Langerhans cells and dendritic cells.
      In addition, IL-10 inhibits T-cell expansion by directly inhibiting IL-2
      production by these cells. These properties of IL-10, together with its capacity
      to downregulate the production of proinflammatory cytokines and chemokines by
      activated monocytes, polymorphonuclear leucocytes and eosinophils, indicate that
      IL-10 is a potent immunosuppressant in vitro. IL-10 has similar activities in
      vivo. It inhibits lipopolysaccharide or staphylococcal enterotoxin B induced
      lethal shock in mice. In addition, IL-10 deficient mice develop chronic
      inflammatory bowel disease, which could be reduced, or prevented by IL-10
      treatment. IL-10 also prevented the development of colitis in a SCID mouse model.
      Collectively, these data indicate that IL-10 has great potential therapeutical
      utility in the treatment of diseases, such as chronic inflammation, autoimmune
      diseases, transplant rejection, graft-versus-host disease and sepsis.

PMID- 8541029
TI  - Progress toward the treatment of arthritis by gene therapy.
AB  - Gene therapy offers several novel advantages to the treatment of arthritis and
      other joint diseases. Therapeutic genes may be delivered locally to diseased
      joints or systemically to extra-articular locations using viral or non-viral
      vectors by ex vivo or in vivo strategies. Pre-clinical experiments with rabbits
      have demonstrated the utility of using a retrovirus to deliver the human
      interleukin-1 receptor antagonist to the synovial lining of joints. A human trial
      based on this principle has been approved by the Recombinant DNA Advisory
      Committee of NIH and should begin this year.

PMID- 8541030
TI  - Hospital discharge register data in the assessment of trends in acute myocardial
      infarction. FINMONICA AMI Register Study Team.
AB  - We evaluated the reliability hospital discharge register data in the assessment
      of acute myocardial infarction trends. In the FINMONICA study areas, trends in
      age standarized attack rates for the years 1983-90 were calculated independently
      from two sources: the nationwide Finnish hospital discharge register and the
      FINMONICA acute myocardial infarction register. The trends were compared by a
      statistical regression model. The trends obtained from the hospital discharge
      register were very similar to the trends obtained from the FINMONICA acute
      myocardial infarction register. The attack rates differed significantly, however,
      and the change in the International Classification of Diseases version from
      version 8 to version 9 brought on a change in the attack rates obtained from the
      hospital discharge register. Thus, hospital discharge register data can be used
      to assess acute myocardial infarction trends in the community. However,
      modifications of the International Classification of Diseases codes (new versions
      of the classification) and changes in the clinical use of the codes for coronary
      heart disease can have an impact on the attack rates obtained from the hospital
      discharge register, and the reliability of the hospital discharge register data
      should be regularly assessed.

PMID- 8541031
TI  - Debrisoquine oxidation polymorphism in patients with chronic inflammatory bowel
      disease.
AB  - Polymorphic hydroxylation of debrisoquine (DBQ) is a Mendelian genetic trait
      related to the risk of suffering some spontaneous disorders. To elucidate whether
      such a relation exists between this polymorphism and chronic inflammatory bowel
      disease (CIBD), 67 (39 males) patients with ulcerative colitis (UC), 52 (35
      males) patients with Crohn's disease (CD) and 837 healthy controls (391 males)
      received 10 mg debrisoquine. DBQ and its metabolite, 4-OH-DBQ, were measured in
      urine to calculate metabolic ratio. Subjects with MR < 12.6 (log 10 MR < 1.1)
      were extensive metabolizers (EM) of DBQ, whereas those with MR < 12.6 were poor
      metabolizers (PM). Four UC (5.97%), 1 CD (1.92%) patients and 42 controls (5.03%)
      were PM of DBQ (nonsignificant difference). When analysing the EM subjects
      separately, log10 MR were lower in controls (mean = -0.295, SD 0.427, P =
      0.0015)) and in Crohn's disease patients (man = -0.281, SD 0.495, P = 0.03) than
      in ulcerative colitis patients (mean = -0.085, SD = 0.495). There is no
      relationship between oxidative phenotype of DBQ and the risk for CIBD.
      Nevertheless, the EM phenotype includes both homo- and heterozygote genotypes for
      functioning alleles exerting a gene-dose effect that gives a higher oxidative
      capability to homozygote EMs, reflected in a lower MR value. Genotyping studies
      are needed to disclose whether heterozygote EMs are over-represented among UC
      patients and to identify any nonfunctioning allele possibly linked to the risk of
      developing this disease.

PMID- 8541032
TI  - Intrastrain differences in Helicobacter pylori: a key question in mucosal damage?
AB  - Helicobacter pylori causes persistent infection and inflammation in the human
      stomach, yet only a small fraction of infected people develop illness. An
      important question is why this diversity exists in infection outcome. In recent
      years, there has been evidence of substantial phenotypic as well as genotypic
      diversity of H. pylori. Three different phenotypes--production of vacuolating
      cytotoxin, presence of cagA, and ability for strong PMN activation--appear to be
      linked to one another and to the propensity for a H. pylori strain to cause
      peptic ulcer disease. Further investigation in this field may help to define
      which infected people bear the highest risk for serious clinical consequences,
      and ultimately to define optimal vaccine candidates and strategies.

PMID- 8541033
TI  - Helicobacter pylori in peptic ulcer: have Koch's postulates been fulfilled?
AB  - This brief review considers whether or not Koch's postulates have been fulfilled
      for Helicobacter pylori and peptic ulceration. The histological features of
      peptic ulcer disease in man are active chronic gastritis with antral
      predominance, duodenal gastric metaplasia and active duodenitis. Other features
      are hyperpepsinogenaemia, relative postprandial hypergastrinaemia and basal acid
      hypersecretion. The macroscopic features are duodenal bulb ulceration or lesser
      curve and antral gastric ulceration. At present, gastric colonization with H.
      pylori has been produced in small animal species (rats and mice), but the
      infection is difficult to establish in immunocompetent animals, and histological
      gastritis is unconvincing. In larger animals the germ-free pig has been the most
      reliable model but the gastritis tends to be chronic with little activity. The
      best examples of acute infection are in three 'self-administration' experiments
      in humans. In these cases acute gastritis with hypochlorhydria developed which,
      when it converted to active chronic gastritis, tended to be asymptomatic. Either
      the circumstances were incompatible with ulceration, or the experiments were not
      continued for the many years necessary to develop peptic ulceration. It is
      concluded that only one of the many steps required for the development of peptic
      ulceration has so far been fulfilled, i.e. the ability of H. pylori to produce
      histological gastritis in a susceptible host.

PMID- 8541034
TI  - The somatostatin-gastrin link of Helicobacter pylori infection.
AB  - Helicobacter pylori is the new-found cause of duodenal ulcers (DU), but acid
      secretion remains necessary and is elevated in DU patients. My group and others
      have asked whether H. pylori itself alters gastric physiology. This infection has
      been found to decrease local expression of the inhibitory peptide somatostatin,
      and to increase release of the acid-stimulating hormone gastrin. H. pylori
      infection can alter acid secretion in both directions. Acid disappears
      temporarily on first infection, and may dwindle later if H. pylori causes gastric
      atrophy. DU patients have approximately twice the normal parietal cell mass,
      which increases their maximal secretory capacity, but it is not clear whether or
      not this is due to H. pylori. However, the infection certainly does change
      physiological control of acid secretion, as expected from the endocrine changes.
      Acid secretion is elevated during fasting, during stimulation with an acidic meal
      and during infusions of gastrin-releasing peptide. The balance between these
      opposing effects of H. pylori on acid may be crucial in determining the clinical
      outcome of H. pylori infection. High-acid secretion leads to DUs whilst low acid
      secretion is found in patients with gastric ulcers and gastric cancer.
      Inflammatory cytokines released in H. pylori gastritis may cause some of these
      changes in gastric physiology.

PMID- 8541035
TI  - Helicobacter infections in laboratory animals: a model for gastric neoplasias?
AB  - Evidence is rapidly accumulating that Helicobacter pylori is a major risk factor
      for human gastric adenocarcinomas and all low-grade B-cell gastric lymphomas.
      Given this, there is a need to develop animal models with a view to discovering
      not only how carcinogenesis is initiated, but also how the process can be
      prevented. The lack of H. pylori animal models suitable for long-term studies
      means that alternatives are needed. The most productive models are likely to be
      the Helicobacter mustelae-infected ferret or the mouse infected with either
      Helicobacter felis or 'Helicobacter heilmannii'. The first evidence that
      helicobacter infection induces a chronic inflammation that progresses to gastric
      atrophy, the precursor lesion to gastric adenocarcinoma in humans, has come from
      the mouse model. The severity of inflammation is dependent on the type of mouse
      strain used, highlighting the importance of host factors in the development of
      gastritis. Carcinogenesis studies should only be done with mouse strains known to
      cause atrophy. The H. mustaelae-infected ferret appears very susceptible to the
      development of adenocarcinoma following ingestion of chemical carcinogens. Long
      term infection of mice with H. felis results in the development of low-grade B
      cell gastric lymphomas indistinguishable to those found in H. pylori-infected
      humans. Helicobacter-infected animals, rodents in particular are going to provide
      exciting opportunities to investigate not only important aspects of gastric
      cancer and lymphoma but also fundamental issues of carcinogenesis in general.

PMID- 8541036
TI  - Alcohol metabolism in Helicobacter pylori-infected stomach.
AB  - Studies in our laboratory have revealed that Helicobacter pylori exhibits
      significant cytosolic alcohol dehydrogenase activity and that the enzyme is fully
      active at ethanol concentrations prevailing in the stomach during alcohol
      consumption or after alcohol is completely absorbed from the stomach and is
      available through blood circulation only. Moreover, even the low levels of
      endogenous ethanol found in the stomach can be oxidized to acetaldehyde by H.
      pylori alcohol dehydrogenase. The metabolic significance of the enzyme remains as
      yet unresolved. Under microaerobic conditions, however, the enzyme could be of
      importance in the energy metabolism of the organism. In the presence of excess
      ethanol, H. pylori alcohol dehydrogenase produces significant amounts of
      acetaldehyde. Acetaldehyde is a toxic and reactive compound and could
      theoretically be a pathogenetic factor in H. pylori-associated gastric injury.
      Preliminary studies have indicated that acetaldehyde inhibits gastric mucosal
      regeneration and forms stable adducts with mucosal proteins. Both of these
      mechanisms could cause gastric injury. The role of H. pylori-related acetaldehyde
      formation in vivo, however, needs to be established in future studies. In antral
      human gastric mucosa, H. pylori infection is associated with a significant
      decrease in alcohol dehydrogenase activity. Similarly, in specific pathogen-free
      mice with a prolonged infection, gastric alcohol dehydrogenase activity is
      decreased; however, this is not clearly reflected in the bioavailability of
      ethanol or the amount of its first pass metabolism.

PMID- 8541037
TI  - Helicobacter pylori, duodenal ulcer, gastric cancer: tunnel vision or blinders?
AB  - The focus of this paper is on the relationship between Helicobacter pylori
      gastritis and gastric cancer, one of the most compelling issues after the recent
      decision of the IARC (International Agency for Research on Cancer) to categorize
      H. pylori as a carcinogen. Our aim is to identify areas where additional work is
      not needed and suggest new directions of inquiry. We review what has been
      accomplished with the advantage of hindsight. Our review of the data regarding
      current putative virulence factors found that disease and outcome specificity
      were lacking. The same can be said of the data regarding low gastric juice
      ascorbate or increased mucosal cell turnover in H. pylori gastritis. We conclude
      that, while it is certainly possible that some of the factors discovered to date
      may initiate or mediate certain pathogenetic aspects of H. pylori-related
      disease, none of them can be seriously proposed as the factor responsible for
      either gastric cancer or duodenal ulcer. Finally, we identified research areas
      that might lead to disease-specific associations as well as areas where
      helicobacters may be used as models for other diseases. We propose that it is
      time to pause, reflect on what has been done, and focus more sharply on the
      questions that remain unanswered.

PMID- 8541038
TI  - Geographical pathology of Helicobacter pylori infection: is there more than one
      gastritis?
AB  - Helicobacter pylori is the aetiological agent of chronic gastritis and a major
      causative factor in duodenal and gastric peptic ulcer disease; a strong
      association also exists with gastric cancer and primary gastric lymphoma. The
      prevalence of infection in adults ranges from less than 15% in developed
      countries to virtually 100% in less developed areas. If H. pylori infection alone
      was responsible for the development of gastritis, peptic ulcer disease, gastric
      carcinoma and primary gastric lymphoma, one would expect the frequency of all
      these conditions to parallel closely the prevalence of H. pylori infection. This
      is clearly not the case: therefore, genetic, environmental and cultural factors
      must act in concert with H. pylori to induce different outcomes of the infection.
      This paper outlines the geographic approach to the study of disease and discusses
      the possible application of this methodology to the inquiry into the relationship
      between H. pylori, atrophic gastritis and gastric cancer. Preliminary results of
      a study showing great variation in the prevalence of intestinal metaplasia in
      duodenal ulcer patients from different geographic origin are presented and
      briefly discussed.

PMID- 8541039
TI  - New options in eradication of Helicobacter pylori.
AB  - Better treatment options to eradicate Helicobacter pylori are needed, while we
      await a possible effective vaccine against the world's most common infection. The
      goals of therapy for H. pylori infection should be an effective and low-cost
      therapy with a low frequency of side-effects. The currently available eradication
      regimens are cumbersome, which can lead to a reduction of compliance and a lower
      efficacy. More recent studies have shown, however, that the duration of
      antimicrobial treatment may be shortened, which also makes the treatment more
      cost-effective and more tolerable. At this point it seems relevant to treat H.
      pylori infection first with some antisecretory modification of triple therapy,
      while the therapeutic failures can be treated with other more relevant and
      suitable alternatives. Metronidazole is still a cornerstone of triple therapy and
      the more expensive clarithromycin is an alternative second-line treatment. Time
      will show the effectiveness and suitability of the latest topical 1-day
      treatments.

PMID- 8541040
TI  - Antibody titres in Helicobacter pylori infection: implications in the follow-up
      of antimicrobial therapy.
AB  - Regular presence and persistence of specific serum antibodies in Helicobacter
      pylori infection gives an excellent tool for diagnostic work. Eradication of the
      infection leads to gradual disappearance of the gastritis and decrease of
      specific serum antibodies. The fall of IgG and IgA antibody titres can be
      followed with quantititative enzyme immunoassays. Success in eradication is
      reflected in 40-50% decrease of antibody titres within 5-6 months. The decrease
      continues and most patients have normal titres within 2 years. Serology offers a
      cheap and convenient way to follow the treated patients and makes most follow-up
      endoscopies unnecessary.

PMID- 8541041
TI  - Incidence of gastric cancer and prevalence of chronic gastritis in outpatients:
      comparison between two geographical areas in Finland.
AB  - We present some evidence that there exists a positive relationship between the
      incidence of gastric cancer and the prevalence rate of chronic gastritis,
      regarding the time trends and geography of these diseases in Finland. Both
      gastric cancer and chronic gastritis have declined in occurrence during the last
      15 years, and there exists a similar geographic distribution of these diseases in
      Finland on the north-south axis: both are more prevalent in Lapland than in
      Southern Finland. The distribution of the socioeconomic conditions in Finland
      also shows a north-south axis: the proportion of people with low social class,
      number of children (birth rate) per household is higher, and the yearly income on
      average is lower in Lapland than in Southern Finland. We conclude that the
      epidemiology of chronic gastritis and gastric cancer show similar epidemiological
      features, regarding at least the time trends and geography of these diseases in
      Finland.

PMID- 8541042
TI  - Helicobacter pylori infection in Estonian population: is it a health problem?
AB  - The role of Helicobacter pylori infection in traditionally noncommunicable
      diseases as chronic gastritis, peptic ulcer and gastric carcinoma became more
      evident during the first decade of H. pylori studies. To analyse and evaluate the
      prevalence of H. pylori infection in Estonia as a population health problem, the
      data of three randomly selected samples of Estonian population aged over 15 years
      were used. The infection rate assessments in two representative samples of the
      population (Kambja 157 persons and Kuressaare 224 persons) were based on H.
      pylori colonization in the gastric mucosa, and in one sample (Karksi-Nuia 1467
      persons) on seroconversion of H. pylori IgG antibodies. The persons studied were
      divided into groups according to birth cohorts. The population studies in Estonia
      showed a high prevalence of H. pylori infection among Estonians: 73% in the
      Kuressaare sample, 78% in the Kambja sample, and 87% in the Karksi-Nuia sample.
      From the Kuressaare population sample 38 families with 290 persons were included
      in a family H. pylori infection study and 92.5% of the persons in these families
      were found to be H. pylori positive. H. pylori infection was frequent in persons
      who were born at the beginning of this century as well as in those born after
      World War II up to 30 years ago. It was concluded that H. pylori infection is
      common in Estonia, both in random persons and their families. It is probable that
      the infection rate of H. pylori depends to a great extent on the socioeconomic
      conditions of this country and that acquisition of H. pylori in Estonia starts at
      an early age.

PMID- 8541043
TI  - What are the specific features of Helicobacter pylori gastritis in children?
AB  - Children with recurrent abdominal pain and dyspeptic symptoms often present
      histological gastritis and Helicobacter pylori infection. No specific
      symptomatology has been found, however, to discriminate H. pylori positive from
      negative subjects. Certain differences exist in gastritis in paediatric age
      groups, in comparison with adults. In terms of treatment, children also form a
      special entity because of the long exposure time of H. pylori infection. This
      article describes the typical findings of H. pylori gastritis in children and
      discusses their significance from a clinical point of view.

PMID- 8541044
TI  - [The flows of migrants in Italy].

PMID- 8541045
TI  - [Epidemiology and migration in Italy: the epidemiological and statistical
      problems].

PMID- 8541046
TI  - [Immigration and health: the regulative aspects].

PMID- 8541047
TI  - [Public health in regard to the immigration phenomenon].

PMID- 8541048
TI  - [Transcultural mental health: the psychopathological risk factors for immigrants
      and interventions for protection].

PMID- 8541049
TI  - [Traditional medicine: its influence on the concepts of health and disease].

PMID- 8541050
TI  - [The human transparent and the human veiled: the therapeutic relationship with
      the heterocultural patient].

PMID- 8541051
TI  - Migration and international health policies.

PMID- 8541052
TI  - [The health policy on immigration in Italy].

PMID- 8541053
TI  - [The relationship between heart rate variability, clinical and coronary
      angiographic parameters, ventricular function, arrhythmia profile and late
      potentials in patients with a recent myocardial infarct].

PMID- 8541054
TI  - [The effect of coronary revascularization on the evolution of heart rate
      variability after a myocardial infarct. An evaluation in the time course and by
      spectral analysis].

PMID- 8541055
TI  - [Radiofrequency ablation in 53 accessory anteroseptal pathways using the approach
      from the right atrium].

PMID- 8541056
TI  - [Catheter ablation of atrioventricular nodal reentry tachycardia: the results of
      a mixed electrophysiological/anatomical technic].

PMID- 8541057
TI  - [The radiofrequency ablation of accessory atrioventricular septal pathways: the
      technics and results].

PMID- 8541058
TI  - [Experience with the Palmaz-Schatz intracoronary stent].

PMID- 8541059
TI  - [Coronary angioplasty in acute myocardial infarct: the immediate results and
      follow-up].

PMID- 8541060
TI  - [The effect of the implantation of a Wiktor stent on the curvature of 2 coronary
      segments. A medium-term follow-up].

PMID- 8541061
TI  - [The effect of the implantation of a Wiktor stent on the flow in the lateral
      coronary branches. A medium-term follow-up].

PMID- 8541062
TI  - [Myocardial hypertrophy due to isoproterenol. The preventive action of
      verapamil].

PMID- 8541063
TI  - [A myocardial lesion induced by hydralazine].

PMID- 8541064
TI  - [The value of magnetic resonance in the diagnosis of hypertrophic
      myocardiopathy].

PMID- 8541065
TI  - [The analysis of negative studies in myocardial perfusion scintigraphy].

PMID- 8541066
TI  - [Neurological complications in coronary surgery in patients who have previously
      undergone carotid endarterectomy].

PMID- 8541067
TI  - [Conservative surgery of the atrioventricular valves with a flexible and
      externally adjustable ring].

PMID- 8541068
TI  - [The rehabilitation of coronary disease--a multifactorial-action program. 2 years
      of experience].

PMID- 8541069
TI  - [Isolated disease of the descending anterior artery: the relationship between the
      angiographic characteristics and the occurrence of angina after myocardial
      revascularization].

PMID- 8541071
TI  - [Severe systolic dysfunction of the left ventricle in acute myocardial infarct-
      an indication for revascularization?].

PMID- 8541070
TI  - [Acute myocardial infarct in diabetic patients: a comparative study].

PMID- 8541072
TI  - [Acute myocardial infarct in the elderly patient: a follow-up].

PMID- 8541073
TI  - [The significance of left ventricular dysfunction in patients with acute
      myocardial infarct complicated by primary ventricular fibrillation].

PMID- 8541074
TI  - [Rupture of the interventricular septum after acute myocardial infarct: the
      clinical and angiography aspects].

PMID- 8541075
TI  - [The relationship between the presentation and classification of unstable angina
      and the clinical and coronary angiographic characteristics and left ventricular
      function].

PMID- 8541076
TI  - [The diagnostic values of serum determinations of troponin T in acute ischemic
      cardiopathy].

PMID- 8541077
TI  - [The oxidative stress produced by acute myocardial infarct and its repercussion
      on lipid peroxidation. The effect of thrombolytic therapy].

PMID- 8541078
TI  - [The effect of thrombolytic therapy on the incidence of left intraventricular
      thrombi after acute myocardial infarct of the anterior wall. A prospective
      multicenter study].

PMID- 8541079
TI  - [An "open" artery after acute myocardial infarct. A relationship to the detection
      of "viable" myocardium by dobutamine stress echocardiography performed
      predischarge?].

PMID- 8541080
TI  - [The effect of collateral circulation on preserving left ventricular function
      after a myocardial infarct].

PMID- 8541081
TI  - [Will the measurement of the value of the pressure half-time be valid in mitral
      stenosis in the elderly patient?].

PMID- 8541082
TI  - [The advantage of determining left ventricular ejection fraction by three
      dimensional echocardiography during the equalization of the ventricular
      pressures].

PMID- 8541083
TI  - [Transesophageal echocardiographic study with three-dimensional reconstruction of
      the left ventricle in dilated cardiopathy. The application of the method and
      calculation of the functional indices].

PMID- 8541084
TI  - [An analysis of the spectral variability of the gray scale by 2-dimensional
      echocardiographic myocardial densitometry as a function of the type and degree of
      left ventricular hypertrophy].

PMID- 8541085
TI  - [Stress echocardiography with dipyridamole/atropine in the detection of
      myocardial ischemia: a comparison with thallium-201 scintigraphy and an
      angiographic correlation].

PMID- 8541087
TI  - [Maximal oxygen consumption measured in the cardiopulmonary stress test versus
      the predicted consumption, for the Bruce protocol].

PMID- 8541086
TI  - [Maximal oxygen consumption measured in the cardiopulmonary stress test versus
      the predicted maximal consumption: an evaluation of 3 protocols].

PMID- 8541088
TI  - [Scientific societies and professional associations. What type of relationship?].

PMID- 8541089
TI  - Helping the relatives of patients with cancer.

PMID- 8541090
TI  - Pharmacokinetic modelling--a prelude to therapeutic drug monitoring for all
      cancer patients?

PMID- 8541091
TI  - The impact of cancer on key relatives: a comparison of relative and patient
      concerns.
AB  - This study examines the impact of diagnosis on key relatives of 108 newly
      diagnosed cancer patients. Cancers of the breast, colon, female reproductive
      tract and testicle were included. Relatives completed a self-report checklist of
      concerns and the General Health Questionnaire (GHQ) (28 items). Patients were
      administered a corresponding concerns checklist as part of a semi-structured
      interview. More relatives than patients expressed each of the nine common
      concerns; the discrepancy was greatest for concern about the patient's emotional
      reaction, reported by 95% of relatives and only 18% of patients. The total
      relatives' concern score (median 16.0) was significantly greater than the
      patients' score (median 4.0) (P < 0.0001). Cancer type, age of patient and nature
      of relationship to patient had little impact on the frequency of relatives'
      concerns. 52 (48%) relatives scored above the usual cut-off on the GHQ,
      suggesting significant psychological morbidity. Relatives of newly diagnosed
      cancer patients report high levels of concerns and psychological distress, and
      deserve greater attention than they currently receive.

PMID- 8541092
TI  - Genetic factors in the aetiology of malignant mesothelioma.

PMID- 8541093
TI  - Spinal cord compression: from laboratory to clinic.

PMID- 8541094
TI  - Fifth International Conference on Adjuvant Therapy of Breast Cancer, St Gallen,
      March 1995. International Consensus Panel on the Treatment of Primary Breast
      Cancer.

PMID- 8541095
TI  - EORTC Early Drug Development Meeting 1995, 21-24 June, Corfu, Greece.

PMID- 8541096
TI  - Anaplastic large cell lymphoma (CD30+/Ki-1+). Analysis of 35 cases followed at
      GISL centres.
AB  - Between January 1988 and June 1992, 35 patients with primary anaplastic large
      cell lymphoma (ALCL)CD30+ were referred to one of the institutions participating
      in GISL (Gruppo Italiano per lo Studio dei Linformi). 16 patients were treated
      with ProMACE-CytaBOM, two with MACOP-B, one with CHOP and one with LSA2-L2. As of
      November 1990, all newly diagnosed patients were treated with MOPP/EBV/CAD
      hybrid. 27 (77%) cases of ALCL CD30+ and 8 (23%) cases of Hodgkin's-related (HR)
      lymphoma CD30+ were diagnosed. Extranodal disease was present in 22 cases (63%),
      and 8 patients (23%) had primary bone marrow involvement. Twenty-three complete
      remissions (CR) (66%), six partial remissions (PR) (17%) and six no remissions
      (NR) (17%) were achieved with induction therapy. Results achieved with ProMACE
      CytaBOM and MOPP/EBV/CAD hybrid were comparable. The overall response rate
      (CR+PR) was 85% for patients with classic ALCL CD30+ and 87% for those with HR
      lymphoma CD30+. The 3 year estimated overall survival rate was 66% and the 3 year
      relapse free survival rate was 65% for the entire group. The only significant
      favourable prognostic factor was the achievement of CR with initial therapy. Our
      findings suggest that ALCL (CD30+/Ki-1+) has a clinical outcome similar to
      aggressive non-Hodgkin's lymphoma (NHL). The use of an anthracycline-containing
      regimen will provide a change of cure in approximately 65% of cases.

PMID- 8541097
TI  - A non-invasive test for the pre-cancerous breast.
AB  - This paper describes a non-invasive, self-measured procedure by which the
      precancerous breast can be distinguished from the normal breast. The method
      involves wearing a specially designed thermometric brassiere for 90 min each
      evening at home through one menstrual cycle. Profiles of progesterone through the
      cycle, obtained from daily saliva sampling, and determination of the steroid
      content by radioimmunoassay, are made to allow the status and calendar date
      timing of the luteal phase to be established. Thus, cycles can be synchronised
      across subjects. In this study, two types of breast were compared: 50 normal
      breasts and 41 age-matched precancerous breasts. Differences between the groups
      were striking in terms of amplitude, phasing and average temperature during the
      luteal heat cycle. When these parameters and others were used as predictors in a
      linear discrimination and/or neural net analysis, a sensitivity and specificity
      of > 90% was achieved.

PMID- 8541098
TI  - Continuous infusion of vincristine, ifosfamide and epirubicin over 6 weeks in
      treatment-resistant advanced breast cancer.
AB  - 28 patients with recurrent advanced breast cancer were treated with a salvage
      regimen consisting of vincristine, epirubicin and ifosfamide/mesna (VIE). All
      patients had poor prognostic characteristics defined as relapse within 12 months
      of chemotherapy or as relapse within a radiotherapy field. Chemotherapy was
      infused continuously through a central venous catheter using a portable pump.
      Ifosfamide (3 g/m2) mixed with mesna (3 g/m2) was infused for 7 days followed by
      epirubicin (50 mg/m2) mixed with vincristine (1.5 mg/m2) over a further seven
      days and alternated for a total of 6 weeks. 9 of the 28 patients (32%) responded
      to VIE (six partial and three complete responses). This included 6 of the 18
      patients (33%) who had previously received doxorubicin or mitoxantrone, 6 of the
      17 patients (35%) who had an inoperable in-field relapse after radiotherapy for
      locally advanced cancer, and 5 of the 21 patients (24%) relapsing within 6 months
      of previous chemotherapy. Median duration of response and overall survival were
      3.7 and 6.9 months, respectively. Myelotoxicity was mild. One patient had
      neutropenic sepsis, 3 patients ahd grade 3 nausea and vomiting and one patient
      developed paralytic ileus attributed to vincristine. Central venous catheter
      complications occurred in 12 of 33 catheters requiring removal in 6. Continuous
      infusional chemotherapy using vincristine, epirubicin and ifosfamide achieves a
      32% overall response rate in treatment-resistant advanced breast cancer, and is
      associated with minimal toxicity and a short treatment period. VIE may be a
      suitable alternative to conventional chemotherapy.

PMID- 8541099
TI  - A phase II study of carboplatin and hexamethylmelamine as induction chemotherapy
      in advanced epithelial ovarian carcinoma.
AB  - 27 patients with ovarian cancer FIGO stages IIc-IV were treated with carboplatin
      7 x (glomerular filtration rate + 25) mg given intravenously on day 1 and
      hexamethylmelamine (HMM) 150 mg/m2 orally on days 2-15, every 28 days. 3 patients
      were not evaluable for response. Clinical response was seen in 17 patients (71%),
      with six (25%) complete and 11 (46%) partial responses. The median progression
      free survival was 15.6 months and the median cancer-related survival was 21.3
      months. 4 patients (15%) experienced grade 3 mental depression; none had
      peripheral neuropathy above grade 1. The haematological toxicity was moderate,
      none had grade 4 leucopenia, but 4 (15%) had grade 4 thrombocytopenia.
      Carboplatin plus HMM had few side-effects and a high response rate with a
      survival comparable to other platinum-based combinations.

PMID- 8541100
TI  - Phase II study of infusional cisplatin in combination with etoposide in the
      treatment of small cell lung cancer.
AB  - The efficacy of a 5 day continuous infusion of cisplatin, 25 mg/m2/day, in
      combination with a bolus infusion of etoposide, 100 mg/m2/day over 2 h for 3 days
      (PiE therapy), was evaluated in a phase II study of previously untreated patients
      with small cell lung cancer (SCLC). There were 39 evaluable patients, of whom 17
      had limited disease (LD) and 22 extensive disease (ED). The overall response rate
      was 92% (LD, 100%; ED, 86%). The complete response rate was 21% (LD, 41%; ED,
      5%). The median survival time was 45.6 weeks (LD, 123.2 weeks; ED, 28.8 weeks).
      The major side-effects were grade 3 or 4 leucopenia (55%), neutropenia (88%) and
      thrombocytopenia (20%). There were no episodes of bleeding, severe infection or
      treatment-related deaths. PiE therapy was associated with significant
      myelosuppression, but was effective, with an especially encouraging response rate
      and survival for LD patients.

PMID- 8541101
TI  - The use of non-proven therapy among patients treated in Norwegian oncological
      departments. A cross-sectional national multicentre study.
AB  - A national multicentre study was performed to investigate the prevalent use of
      "alternative medicine", here called "non-proven therapies (NPT)", applied among
      Norwegian cancer patients. Of 911 patients invited to take part in the study, 642
      were included in the analysis. Demographic characteristics were collected for all
      patients. The participating physicians gave information about the patients'
      clinical characteristics. Among 630 evaluable patients, 20% had been or were
      present users of NPTs for their oncological disease. The preferred methods were
      healing by hand and faith healing. Herbs, vitamins, diets and Iscador were other
      popular methods. As many as 40% of the users of NPTs had used NPTs earlier for
      non-malignant diseases. Elderly patients were less likely to use NPTs. Use was
      high in the northern part of Norway.

PMID- 8541102
TI  - Disease monitoring by the tumour markers cyfra 21.1 and TPA in patients with non
      small cell lung cancer.
AB  - We evaluated the use of two tumour markers Cyfra 21.1 and tissue polypeptide
      antigen (TPA) for disease monitoring. Assessment of response to WHO criteria was
      compared to response assessment according to changes in the tumour marker levels.
      The criteria defined for marker response were a 65% decrease for a partial
      response and a 40% increase for progressive disease. When response evaluations
      with a positive lead time were included, 72% of 115 evaluations for Cyfra 21.1
      and 59% of 107 evaluations for TPA yielded the same result. Most discordant
      evaluations were caused by those evaluations whereby the patient achieved a
      partial response according to the WHO criteria and had normalisation of the
      marker. Less cases with a positive lead time, more negative lead times, and more
      patients with progressive disease without an increase of the marker were seen
      with TPA compared to Cyfra 21.1. In conclusion, Cyfra 21.1 follows the changes in
      the tumour load better than TPA. Rising levels of both markers nearly always
      indicate disease progression, and such knowledge easily obtained may prevent the
      continuation of ineffective treatment.

PMID- 8541103
TI  - Limited sampling models for reliable estimation of etoposide area under the
      curve.
AB  - Limited sampling models are able to estimate the area under the concentration
      time curve (AUC) from plasma concentrations measured at only a few time points.
      The purpose of this study was to establish a model estimating etoposide AUC
      independently of specific chemotherapy protocols, underlying malignancies,
      concomitant diseases and age. Pharmacokinetic parameters were measured in 30
      patients treated with polychemotherapy including etoposide (80-150 mg/m2).
      Etoposide analysis was performed by thin layer chromatography and consecutive
      quantitative sample detection by 252Cf-plasma desorption mass spectrometry. Data
      from the first 15 patients formed the training set. Based on the training data,
      five different models were generated, with the multiple regression coefficient r
      ranging from 0.91 to 0.96. The following model was selected as "most accurate":
      AUC = 343 (min)C4h(micrograms/ml) + 650(min)C8h(micrograms/ml) + 1252 (min
      micrograms/mol), where C4h is the plasma concentration of etoposide at 4 h after
      the end of infusion and C8h at 8 h. This model was validated on the test set,
      comprising the data of the remaining 15 patients. The mean predictive error (MPE)
      was -0.2% and the root mean square predictive error (RMSE) was 4.7%. When used
      for a large number of patients, this practicable and simple model is an
      instrument for use in prospective studies, to measure a correlation between drug
      dosage and efficacy or toxicity of the drug.

PMID- 8541104
TI  - Reduction of metastatic carcinoma cells in bone marrow by intravenously
      administered monoclonal antibody: towards a novel surrogate test to monitor
      adjuvant therapies of solid tumours.
AB  - In a pilot, prospective randomised study, 40 patients with breast and colorectal
      cancer presenting with metastatic cytokeratin (CK)-positive tumour cells in bone
      marrow were treated either with six doses of 100 mg of a monoclonal Lewis Y
      antibody during 2 weeks or with a placebo regimen, consisting of six infusions of
      human serum albumin (HSA). CK-positive cells in marrow were monitored prior to
      and on days 15 and 60 after commencement of treatment. In 30 patients presenting
      with relatively low tumour cell numbers (1-11 per 4 x 10(5) bone marrow cells), a
      therapy-induced reduction of CK-positive cells could not be conclusively
      determined. More meaningful quantitative data were obtained in 10 breast cancer
      patients presenting with more than 20 tumour cells per 4 x 10(5) nucleated bone
      marrow cells. 7 of these patients had been randomised to the antibody arm, and 5
      showed an eradication or a distinct reduction of CK-positive/Lewis Y-positive
      cells of at least one log unit, while 2 patients, presenting with Lewis Y
      negative tumour cells, showed no corresponding decrease. Similarly, in all 3
      patients randomised to the placebo arm, tumour cells were not reduced. Because
      the antibody exerted a marked cytotoxicity on tumour cell lines when tested ex
      vivo in serum taken from these patients after antibody infusion, we postulate
      that the observed, prompt reduction of individual tumour cells in bone marrow was
      due to the cytotoxic action of the injected antibody. Although monitoring
      micrometastatic cells in bone marrow of patients with high tumour cell counts
      appears to be feasible, the immunocytochemical assay needs to be improved for
      patients with lower cell numbers before it can be applied as a surrogate test for
      adjuvant therapies.

PMID- 8541105
TI  - Comparison of methods for the estimation of carboplatin pharmacokinetics in
      paediatric cancer patients.
AB  - The antitumour and toxic effects of platinum drugs, in particular carboplatin,
      have been related to their plasma concentration and this has led to the concept
      of a target area under the plasma concentration-time curve (AUC) for carboplatin
      dosing. A formula based on renal function has been successfully applied to
      carboplatin dosing in adults and modified versions have also been proposed for
      paediatric patients. In order to monitor carboplatin AUC with maximum efficiency
      and minimum patient inconvenience, limited sampling strategies are desirable. A
      population method with Bayesian estimation is described, based on one or two
      samples taken following a dose of carboplatin. Population data were obtained from
      22 paediatric patients treated with 200-1000 mg/m2 carboplatin as a 60-90 min
      infusion. Ultrafilterable carboplatin was determined by atomic absorption
      spectrophotometry. A two compartment model was fitted to each data set using the
      Maximum Likelihood estimator of the ADAPT programme. These parameter estimates
      provided the prior means and covariance matrix for the Bayesian estimator using a
      lognormal distribution. The test data sets consisted of ultrafilterable
      carboplatin concentrations in 23 patients (aged 1 month-18 years) who received
      similar treatment. The two compartment model was fitted to data sets containing
      one or two points, using the Bayesian maximum a posteriori (MAP) estimator and an
      error model derived from the population error model parameters. Results from the
      Bayesian analysis and other methods for the estimation of AUC, including relating
      clearance to surface area or to renal function, were evaluated by comparing the
      AUC estimate with the AUC determined by model-independent analysis. Overall, the
      optimal sampling strategy performed better than estimates based on renal
      function, which had a median bias of 5% and precision of 22%. With one data point
      at 60 min postinfusion, the median bias and precision were 3 and 6%,
      respectively. Addition of a second data point at 30 min during the infusion
      improved the estimate slightly (median bias -2%, precision 3%). Bayesian
      estimation produced more reliable estimates of AUC compared to values based on
      renal function, which in turn was slightly better than using surface area. A
      technique, developed in adult patients, for estimating AUC from a measurement of
      24 h total plasma platinum was comparable to estimates based on renal function,
      but was less reliable. The estimation of carboplatin AUC can be performed using
      only one or two plasma samples and Bayesian analysis. This approach is less
      biased and more precise than methods based on surface area, renal function or
      total platinum at 24 h postdose, but is probably best used in combination with
      dosing based on renal function.

PMID- 8541106
TI  - Childhood and adolescent cancer in Spain: mortality time trends 1956-1990.
AB  - Using log-linear Poisson modelling, trends in childhood cancer mortality among
      the population under 20 years of age in Spain are described over the 35-year
      period from 1956 to 1990. Overall cancer mortality and seven specific sites were
      considered: all leukaemias, Hodgkin's disease, non-Hodgkin's lymphomas, malignant
      brain tumours, kidney cancer, malignant bone neoplasms, and a broad category of
      ill-defined tumours. An age-period-cohort model was used to analyse the influence
      of age, period of death and birth cohort. Recent trends were estimated by
      restricting analysis to the last three 5-year periods. In general, mortality
      began to decline at the beginning of the 1970s, with reductions of 36% in males
      and 45% in females being registered between 1966-1970 and 1986-1990. The use of
      age-period-cohort models revealed an initially rising period effect attributable
      to diagnostic advances. The decline in mortality in post-1965 generations and the
      final downturn in the period effect are both most certainly a consequence of the
      remarkable progress achieved in the treatment of such tumours. During the final
      15 years, there was a relative decline in mortality of approximately 20% every 5
      years. However, in the case of malignant renal tumours in males and malignant
      bone tumours and non-Hodgkin's lymphomas in both sexes the situation remained
      stable.

PMID- 8541107
TI  - Cancer incidence in The Netherlands in 1989 and 1990: first results of the
      nationwide Netherlands cancer registry. Coordinating Committee for Regional
      Cancer Registries.
AB  - The first results are presented of the newly established Netherlands Cancer
      Registry, which covers the whole Dutch population (approximately 15 million
      people). The registry receives data on incident cancer cases from nine autonomous
      regional cancer registries. Notification occurs primarily through the national
      registry of all pathology and haematology departments, with additional reporting
      by medical records' departments of all hospitals. Data on cancer patients are
      abstracted directly from the medical records by trained registration clerks. In
      the years 1989-1990, the most common cancer sites among males were cancers of the
      lung, prostate and colon. For females, breast cancer ranked first, followed by
      cancer of the colon and lung. A comparison with age-adjusted (world standard
      population) incidence rates reported by other western cancer registries showed a
      relatively high incidence of lung cancer among males (72.9 per 100,000) and
      breast cancer among females (76.2 per 100,000). Through its near completeness and
      the high quality of the registered data, the Netherlands Cancer Registry offers
      excellent opportunities for epidemiological and clinical research.

PMID- 8541108
TI  - Survival in interval breast cancer in the DOM screening programme.
AB  - The study describes breast cancer survival of 75 interval cancer cases (cancer
      occurring within 2 years of a negative screen) detected in women who participated
      in the DOM screening programme. After mammographic revision, this group was
      divided into 17 so-called 'missed' cases and 58 'true' interval cases. Ten year
      survival of these 58 'true' interval cases was 58%, which was not significantly
      different from that of 219 cancers detected in a non-screened, control group of
      women, diagnosed with breast cancer before the start of screening (63%; log rank
      chi 2 test, P = 0.98). Results remained essentially the same after correction for
      age at diagnosis, tumour size, axillary status and year of diagnosis. Ten year
      survival of 'true' interval cancers (58%) was slightly worse than that of
      'missed' cases (67%; log rank chi 2 test: P = 0.38). This difference could
      largely be explained by differences in tumour size and axillary status. We
      conclude that there was no important difference in survival between 'true'
      interval cancers and non-screened historical controls. This could mean that
      either this subgroup of interval cancers does not constitute an excess of rapidly
      growing tumours, or if it does, that a fast growth rate is not associated with an
      exceptionally poor prognosis.

PMID- 8541109
TI  - Risk factors for the development of oesophageal cancer as a second primary
      tumour.
AB  - Exposure to irradiation or chemotherapy as well as prolonged exposure to risk
      factors, such as alcohol and tobacco, may induce a second primary carcinoma of
      the oesophagus. To estimate the potential risk of previous treatment regimens, we
      performed a case-control study. In the Tumour Registry of The Netherlands Cancer
      Institute, from 1955, 27 cases of squamous cell carcinoma of the oesophagus were
      identified following treatment for malignant lymphoma (n = 11), breast cancer (n
      = 8) and lung cancer (n = 8). The median interval was 6.6 years (range 1-16).
      Preferably 3 controls from the same tumour registry were matched to each case on
      the basis of sex, age, primary tumour, location of primary treatment (academic or
      general hospital), calendar year at diagnosis of primary tumour and duration of
      follow-up. Clinical data and details of treatment were obtained from the medical
      records. In patients who had smoked for more than 5 years, there was a 3.2-fold
      increased risk of oesophageal carcinoma (P = 0.04); for those with a regular
      alcohol intake the relative risk was 3.3 (P = 0.01). There was no significant
      relationship between irradiation of the mediastinum and subsequent risk for
      oesophageal cancer. The number of chemotherapy-treated patients was too small to
      calculate the relative risk associated with cytostatic drugs. In conclusion,
      oesophageal cancer as second primary cancer is extremely rare. Risk factors
      include the well known abuse of alcohol and tobacco. No significant relationship
      with previous mediastinal irradiation could be demonstrated.

PMID- 8541110
TI  - Factors affecting recurrence and progression in superficial bladder tumours.
AB  - Prognostic factors in superficial bladder tumours are highly correlated with each
      other. In this study, their relative importance is examined and grouping of
      patients in three different prognostic groups suggested. 576 patients (from EORTC
      protocols 30790 and 30782) were analysed. They have been followed from 3 months
      to 8.6 years with a median of 4 years. 76 patients developed an invasive tumour
      (> or = T2); the shortest time to invasion was 12 weeks, the longest was 6.6
      years. Time from invasion to death ranged from 3 weeks to 4.4 years with a median
      of 2 years. Prognostic factors contributing to recurrence, invasion and survival
      were investigated: age, sex, size of largest tumour, number of tumours, T
      category, G-grade, time from diagnosis (years), prior recurrence rate/year, site
      of involvement. The relative importance of these factors was measured by
      performing a multivariate analysis based on Cox's proportional hazards regression
      model. Based on the most important prognostic factors and their association with
      invasion and death, an index was computed reflecting the risk of both invasion
      and death due to malignant disease, respectively. The index was used to assign
      patients to one of three prognostic groups. Three main factors determined
      patient's prognosis: tumour size, G-grade and prior recurrence rate/year. The
      model coefficients for invasion were 0.51 (recurrence rate < 1/year, 1-3/year, >
      3/year), 84 (grade 1, 2, 3), 0.48 (size < 1.5, 1.5-3, > 3 cm) and for death due
      to malignant disease 0.89 (recurrence rate), 0.73 (grade) and 0.44 (size),
      respectively. Risk groups are suggested based on the index. Additional treatment
      in patients with superficial transitional cell carcinoma of the bladder may be
      decided depending on the risk group to which the patient belongs.

PMID- 8541111
TI  - p53 in malignant and benign liver lesions.
AB  - p53 expression was studied by immunohistochemical methods in benign and malignant
      human epithelial liver lesions in 46 patients from Hungary. Positive
      immunostaining for p53 protein, indicating the overexpression or prolonged half
      life of p53 protein, was detected in the nuclei of tumour cells of seven of the
      16 hepatocellular carcinomas (HCC) (44%), including three HCC patients with
      hepatitis B virus infection. Immunostaining of p53 was seen in one of the seven
      hepatoblastomas, none of the 17 focal nodular hyperplasias, and none of the six
      hepatocellular adenomas. The detection of p53 in a relatively high percentage of
      the HCC cases in Hungary, a country in which aflatoxin contamination of the diet
      is rare, suggests that factors other than aflatoxin led to the accumulation or
      overexpression of p53 in these patients.

PMID- 8541112
TI  - Is the negative prognostic value of high oestrogen receptor (ER) levels in
      postmenopausal breast cancer patients due to a modified ER gene product?
AB  - Recently, it was found that, among post menopausal breast cancer patients
      receiving no adjuvant therapy, the highest oestrogen receptor (ER) levels (ER++)
      as opposed to the intermediate ER levels (ER+) indicated a poorer prognosis in
      terms of recurrence-free survival (Thorpe et al. Eur J Cancer 1993, 29A, 971
      977). In the present study, we confirm, in a series of 218 node negative,
      postmenopausal patients in whom ER was determined using a one-dose saturating
      method, that ER+ tumours have a more negative effect on disease-free survival
      (DFS) than ER+ tumours (P = 0.02). In another series of 87 ER positive,
      postmenopausal patients, we found a significant correlation (P = 0.04) between
      the ER level and ER+R ratio (ER protein/ER-specific mRNA): the higher the ER
      level, the more numerous the high ER+R ratio cases (ER+R > 1.5), reflecting an
      imbalance between the ER protein level and ER-specific mRNA. From these results,
      we hypothesise that high ER levels related to a high ER+R ratio suggest the
      presence of a modified ER gene product.

PMID- 8541113
TI  - TP53 mutations and abnormal p53 protein staining in breast carcinomas related to
      prognosis.
AB  - Abnormalities in the TP53 tumour suppressor gene were evaluated in 106 unselected
      breast carcinomas and compared to clinical outcome of the disease. Tumours were
      screened for p53 abnormalities using immunohistochemical staining and polymerase
      chain reaction-constant denaturant gel electrophoresis (PCR-CDGE) analysis,
      followed by PCR and direct sequencing. Allelic loss at the TP53 locus was
      determined with polymorphic markers by comparing normal and tumour DNA. For
      approximately half of the patients, abnormal p53 protein expression in serum was
      determined by an ELISA assay. p53 abnormalities, detected as mutations and/or
      nuclear staining, were found in 37.6 (38/101) of cases. Nuclear staining for p53
      protein could be identified in 33.7% of the tumours. Mutations in exons 5-8 were
      detected in 18.9% of the tumours, and an association was found between mutations
      and nuclear staining. Allelic loss in the TP53 region on 17p was more frequent in
      tumours showing changes in the TP53 gene (72.7%) compared to tumours with no
      mutation (45.8%). Serum levels of p53 antibodies showed no association with
      either TP53 mutations or nuclear staining. Women with TP53 mutations in their
      tumours had an elevated risk of dying during the study period (RR (relative risk)
      = 3.4, P = 0.014). The effects of p53 positive staining were similar (RR = 3.2, P
      = 0.013). Considering all abnormalities, mutation and/or staining, the relative
      risk of dying from breast cancer was 3.5 (P = 0.008).

PMID- 8541114
TI  - Adding a reverser (verapamil) to combined chemotherapy overrides resistance in
      small cell lung cancer xenografts.
AB  - Small cell lung carcinomas (SCLC) are characterised by chemosensitivity to
      diverse antitumoral compounds. However, responses are transitory and relapses are
      commonly observed. We examined the ability of verapamil, a reverser of P
      glycoprotein (Pgp)-related resistance, to improve the efficacy of CyCAV combined
      chemotherapy (Cy, cyclophosphamide (CPA); C, cisplatin (CDDP); A, doxorubicin
      (ADM);V, etoposide (VP16)), as currently administered to SCLC patients at
      Institut Gustave-Roussy, France, and adapted to the treatment of nude mice
      implanted with these tumours. Although Pgp encoded by the MDR1 (multidrug
      resistance) gene is not the only mechanism for multidrug resistance (MDR), and
      not all drugs included in this regimen are recognised by Pgp, we anticipated a
      therapeutic benefit. Four different SCLC lines, expressing the MDR1 gene and
      recently grafted into nude mice, were used. SCLC-75, SCLC-6 and SCLC-41
      originated from untreated patients, and SCLC-74T was derived from a patient
      treated with a combination of ADM, CPA and VP16. SCLC-41% and SCLC-6T tumours
      were used after having undergone, respectively, five and nine cycles of in vivo
      passage and CyCAV treatment of the tumour-bearing nude mice, to reinforce their
      chemoresistance. The efficacy of the CyCAV regimen, associated with or without
      verapamil (given 24 h before CyCAV on days 1-5), was tested on the growth of
      these SCLC. Verapamil (25 mg/kg) improved the antitumour effect of CyCAV in mice
      bearing SCLC-6T, SCLC-41T and SCLC-75 tumours, although toxicity was observed.
      Verapamil modestly delayed the plasma clearance of ADM. Two daily injections of
      10 mg/kg of verapamil, administered at a 3 h interval, proved to be effective,
      whereas the same total dose administered as a bolus was not. These results
      indicate that the association of some reversers of MDR, including drugs possibly
      interacting with Pgp, might potentiate SCLC combined chemotherapy.

PMID- 8541115
TI  - Enhancement of ACNU treatment of the BT4An rat glioma by local brain hyperthermia
      and intra-arterial drug administration.
AB  - To evaluate the role of intra-arterial (i.a.) chemotherapy, intravenous (i.v.)
      chemotherapy, and local brain hyperthermia in the treatment of gliomas, the
      effect of i.v. versus i.a. drug delivery, with or without local brain
      hyperthermia, was evaluated in BD IX rats with BT4An gliomas implanted in the
      right frontal lobe. The rats were given ACNU 18 mg/kg i.a. in the right carotid
      artery or i.v. in the inferior cava with or without local microwave hyperthermia
      at 42.4 degrees C for 45 min. ACNU i.v. alone had no notable effect on survival.
      Survival was prolonged when ACNU without hyperthermia was given i.a. instead of
      i.v. (P < 0.05). Thermochemotherapy with ACNU i.a. was more effective than with
      ACNU i.v. (P < 0.01). Survival improved as hyperthermia enhanced the i.v. drug
      effect (P < 0.01), and hyperthermia also improved the i.a. ACNU effect (P <
      0.01). Post-treatment survival was more than doubled for the group given combined
      i.a. ACNU and hyperthermia, compared to controls. Thermochemotherapy,
      particularly with i.a. drug administration, seems to be a promising new approach
      for the treatment of primary brain tumours. However, more knowledge about
      tolerance of human brain tissue to hyperthermia is necessary before this
      treatment modality is used in patients with a reasonable life expectancy.

PMID- 8541116
TI  - Antibodies to LMP2A/2B in EBV-carrying malignancies.
AB  - Antibodies to the Epstein-Barr virus (EBV)-encoded membrane proteins, LMP2A and
      LMP2B, were assayed in 540 individuals, including 154 patients with
      nasopharyngeal carcinoma, 16 with African Burkitt's lymphoma, 113 with Hodgkin's
      disease, 14 with EBV-carrying gastric carcinoma, 14 with oral hairy leucoplakia
      (HIV+ patients), 37 with non-Hodgkin's lymphoma, 49 with tumours of the
      head/neck, 19 with infectious mononucleosis, 62 with chronic illnesses with EBV
      titres consistent with re-activations, and 62 healthy controls. A novel assay,
      mouse monoclonal enhanced indirect immunofluorescence assay (MIFA) was designed
      and used to test the sera for antibodies to the LMP2A and 2B proteins, expressed
      in human keratinocytes. Antibody to both LMP2A and LMP2B was strikingly specific
      to NPC. Virtually all (99 of 101) of the LMP2 antibody positive individuals were
      NPC patients, 95% of whom had antibodies that reacted both with the LMP2A- and
      LMP2B-transfected indicator cells, while the remaining 5% reacted only with the
      LMP2B expressing cells.

PMID- 8541117
TI  - Microsatellite instability in gastric carcinoma with special references to
      histopathology and cancer stages.
AB  - To study the molecular mechanism of gastric carcinogenesis, the frequencies of
      microsatellite instability were evaluated with seven dinucleotide repeat loci in
      59 patients with gastric carcinoma. Microsatellite instability at two or more
      loci was found in 41.5% (17/41) of advanced gastric carcinoma, 21.4% (3/14) of
      early gastric carcinoma, but not in remnant gastric carcinoma (0/4), with an
      overall frequency of 33.9% (20/59). Diffuse gastric carcinoma had a similar
      prevalence (32.1%, 9/28) to intestinal gastric carcinoma (40.7%, 11/27). The
      frequency of microsatellite instability in gastric carcinoma was not
      significantly different with respect to age, sex and Helicobacter pylori
      infection. Microsatellite instability tended to occur more frequently in cancers
      of the cardia (62.5%, 5/8) compared with cancers of other stomach regions (31.9%,
      15/47), but the difference was not statistically significant. These data suggest
      that microsatellite instability occurs in early gastric carcinoma and its
      occurrence increases during tumour progression. Furthermore, its frequency was
      independent of age, gender, histological types and Helicobacter pylori infection.

PMID- 8541118
TI  - Human stem cell factor protects CD34 positive human myeloid leukaemia cells from
      chemotherapy-induced apoptosis.

PMID- 8541119
TI  - Profile of T-cell lymphomas in Ibadan, Nigeria.

PMID- 8541120
TI  - Splenic metastases in patients with portal hypertension.

PMID- 8541121
TI  - Problems with the evaluation of response after induction chemotherapy in breast
      cancer.

PMID- 8541122
TI  - Sequential chemotherapy, beta interferon, retinoids and tamoxifen in the
      treatment of metastatic breast cancer. A pilot study.

PMID- 8541123
TI  - Dose intensification of carboplatin and etoposide as first-line combination
      chemotherapy in small cell lung cancer.

PMID- 8541124
TI  - Salvage chemotherapy in non-dysgerminomatous germ cell tumours of the ovary.

PMID- 8541125
TI  - Lobaplatin in combination with methotrexate and vinblastine in patients with
      transitional cell carcinoma of the urinary tract--a pilot phase I/(II) study.

PMID- 8541126
TI  - Failure to confirm presence of SV40 sequences in human tumours.

PMID- 8541127
TI  - Flow cytometric gating on cytokeratin-containing DNA aneuploid breast cancer
      cells improves the prediction of recurrence.

PMID- 8541128
TI  - Reversible neurotoxicity during interleukin-2 therapy for metastatic renal cell
      carcinoma.

PMID- 8541129
TI  - Clinical significance of serum S100 in metastatic malignant melanoma.
AB  - The clinical significance of serum S100 was assessed in comparison to neuron
      specific enolase (NSE) in 126 patients with malignant melanoma: 80 patients with
      clinical stage I/II, 23 patients with stage III and 23 patients with stage IV
      according to the criteria of the American Joint Committee on Cancer (AJCC). Using
      cut-off values of 0.15 microgram/l for S100 and 12.5 micrograms/l for NSE, the
      sensitivity was found to be 1.3% (1/80) for S100 and 8.75% (7/80) for NSE in
      patients with stage I/II, 8.7% (2/23) for S100 and 13% (8/23) for NSE in patients
      with stage III, and 73.9% (17/23) for S100 and 34.8% (8/23) for NSE in patients
      with stage IV disease (P < 0.05). In 6 patients with stage III/IV tumours, serial
      measurement of serum S100 and NSE was performed. A rise of serum S100 indicated
      progression of the disease; a decline indicated response to treatment. Our
      preliminary results support the value of serum S100 as an adjunct to the clinical
      staging and monitoring of metastatic malignant melanoma.

PMID- 8541130
TI  - Osteoporosis and exercise.

PMID- 8541131
TI  - Bone mineral density in female athletes representing sports with different
      loading characteristics of the skeleton.
AB  - To address the hypothesis that osteogenic effect of physical loading increases
      with increasing strain rates and peak forces, we examined 59 competitive Finnish
      female athletes (representing three sports with different skeletal loading
      characteristics), physically active referents (they reported an average of five
      various types of exercise sessions per week), and sedentary referents (two
      sessions per week) using dual energy X-ray absorptiometry. The measured anatomic
      sites were at the lumbar spine, femoral neck, distal femur, patella, proximal
      tibia, calcaneus, and distal radius. The athlete group consisted of aerobic
      dancers (N = 27), squash players (N = 18), and speed skaters (N = 14). The squash
      players had the highest values for weight-adjusted bone mineral density (BMD) at
      the lumbar spine (13.8% p < 0.001 as compared with the sedentary reference
      group), femoral neck (16.8%, p < 0.001), proximal tibia (12.6%, p < 0.001) and
      calcaneus (18.5%, p < 0.001). Aerobic dancers and speed skaters also had
      significantly higher BMD values at the loaded sites than the sedentary reference
      group, the difference ranging from 5.3% to 13.5%. The physically active
      referents' BMD values did not differ from those of the sedentary referents at any
      site. The results support the concept that training, including high strain rates
      in versatile movements and high peak forces, is more effective in bone formation
      than training with a large number of low-force repetitions.

PMID- 8541132
TI  - A comparison of bone mineral densities among female athletes in impact loading
      and active loading sports.
AB  - The purpose of this study was to compare bone mineral densities (BMD) of
      collegiate female athletes who compete in impact loading sports; volleyball
      players (N = 8) and gymnasts (N = 13), to a group of athletes who participate in
      an active loading sport; swimmers (N = 7), and a group of controls (N = 17). All
      of the volleyball, swimming, and control subjects were eumenorrheic (10-12
      cycles/year), whereas two of the gymnasts were amenorrheic (0-3 cycles/year),
      eight were oligomenorrheic (4-8 cycles/year), and three were eumenorrheic (10-12
      cycles/year). Lumbar spine, proximal femur, and total body BMD were measured with
      dual-energy X-ray absorptiometry. The groups were compared with respect to the
      following regions: lumbar spine (L1-4); femoral neck; Ward's triangle; right and
      left arms; right and left legs; pelvis; and torso. When controlling for
      differences in height and weight the impact loading group (volleyball and
      gymnastic) had significantly greater BMD at the lumbar spine, femoral neck,
      Ward's Triangle, and total body when compared to the active loading (swimming)
      and control groups. The regional analysis from the total body scan revealed that
      the gymnasts had significantly (p < 0.05) greater BMD than all other groups at
      the right and left arm sites. The impact loading groups (gymnastic and
      volleyball) had a greater BMD in the legs and pelvis than the active loading
      (swimming) and control groups. Furthermore, the impact loading group had a
      greater torso BMD than the control group. There were no differences at any site
      between the active loading group (swimming) and control groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8541133
TI  - Bone mass at lumbar spine and tibia in young males--impact of physical fitness,
      exercise, and anthropometric parameters: a prospective study in a cohort of
      military recruits.
AB  - Bone mineral density (BMD) and bone mineral content (BMC) were measured using DXA
      at lumbar spine and tibial diaphyses at the beginning and at the end of a 15-week
      training period in 151 military recruits of the Swiss army belonging to 5
      different troop categories (infantry grenadiers, tank drivers, tank gunners,
      signalmen, and privates) who each were exposed to physical training of various
      intensity. At baseline, height, body mass index, and degree of physical fitness
      independently correlated with vertebral and tibial BMD. Over the 15 weeks of
      physical training BMD at tibial diaphyses increased by 2.2 +/- 0.3% at the left
      leg (p = 0.0001) and by 1.1% at the right leg (p = 0.002) with differences
      between troop categories. At lumbar spine, BMD decreased significantly in tank
      drivers (-1.2 +/- 0.4%, p = 0.001) and particularly in infantry grenadiers (-2.1
      +/- 0.4%) who had the most strenuous weight-bearing training, but not in other
      troop categories. This decrease was twice as large at the center of the vertebra
      than for the whole vertebra. These BMD changes were associated with increments in
      serum levels of osteocalcin and alkaline phosphatase activity. From the initial
      cohort, 48 subjects volunteered for a third investigation carried out 2 years
      after the end of the military training period. At this time, lumbar BMD and BMC
      had risen back to baseline, whereas at tibial diaphyses bone width and BMC but
      not BMD increased by 5.8 +/- 1.1% and 6.2 +/- 0.9%, respectively, vs. baseline (p
      = 0.0001 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541134
TI  - The response of the skeleton to physical training: a biochemical study in horses.
AB  - In this study we tested the hypothesis that exercise induces an adaptive response
      in the developing skeleton which may be monitored in vivo by measuring
      biochemical markers of bone metabolism. The effects of exercise on two
      biochemical markers of bone formation were determined; the carboxy-terminal
      propeptide of type I procollagen (PICP), and the bone-specific isoenzyme of
      alkaline phosphatase (BAP), and one putative marker of resorption, the
      pyridinoline crosslinked telopeptide domain of type I collagen (ICTP). All three
      markers were measured for a year in 2-year-old thoroughbred horses exercised
      three times a week on a treadmill, and values compared to a control group of age
      matched animals. Levels of all three markers fell in both exercised and control
      groups over the 12-month period reflecting normal age changes. However, there
      were differences between groups in the pattern of this decrease. When expressed
      as a percentage of baseline values, BAP was higher (p < 0.05) at 2 months and
      both BAP and the PICP were higher at 4 months (p < 0.01 and p < 0.05,
      respectively) in the exercised group, reflecting an increase in bone turnover in
      this group in the early stages of training. PICP levels were also elevated in the
      exercised group at 10 months and this result indicates an increase in bone
      turnover at this time. The changes in ICTP were different; at 2 months, levels
      were higher in exercised animals than in controls, but there was no significant
      difference between the two groups at 4 and 6 months. After 8 months, ICTP levels
      in the exercised group increased returning to near baseline values at 10
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541135
TI  - Evidence of strain-mode-related cortical adaptation in the diaphysis of the horse
      radius.
AB  - The relative importance that certain strain features, including mode (e.g.,
      tension vs. compression) and magnitude, have in affecting adaptive bone
      remodeling seen in normal skeletally mature bones remains controversial. The
      equine radius is used as a model because in vivo strain data show that the mid-to
      proximal diaphysis receives a consistent history of predominantly cranial-caudal
      bending loads, in contrast to the distal diaphysis which receives relatively more
      torsional loading superimposed on cranial-caudal bending. Medial and lateral
      cortices serve as control regions because they correspond to a neutral axis of
      bending. Equine radii were sectioned transversely at 65% (proximal), 50%, and 35%
      (distal) of length and cortical bone from the cranial ("tension"), caudal
      ("compression"), medial, and lateral regions was examined to determine if one, of
      many, structural and material features could be distinguished as being
      consistently related to the distribution of the prevailing strain modes. Mineral
      content (percent ash) differences, though statistically significant (p < 0.01),
      vary less than 1% between regions of the cortex at all sections. Porosity is not
      significantly different between any of the regions (p = 0.13). In the 65% and 50%
      sections, secondary osteon population density (OPD, osteons per square
      millimeter) and fractional area of secondary bone (FASB) are each nearly two
      times as great in the caudal regions than in the other three regions (p < 0.01).
      The 35% section shows a pattern opposite of that in the other sections--there are
      more than two times as many osteons in the cranial cortex than in the caudal
      cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541136
TI  - The natural history of kyphosis in postmenopausal women.
AB  - A cross-sectional study of vertebral morphometry in 449 unscreened postmenopausal
      women, from the ages of 40 to 80, is reported. The wedge angles of thoracic
      vertebrae T4-12 were found to increase exponentially as a function of age, up to
      70 years. In addition to age, the wedging phenomenon was found to be accentuated
      by increased bone turnover due to low calcium intake, reduced physical activity,
      each successive delivery, and breast feeding. Most of these variables were not
      correlated with isolated vertebral wedge angles, but rather with the sum of them
      (Sigma, sigma), assumed to assess the impact of those variables on thoracic
      kyphosis. In a subset of women, sigma was found to be inversely correlated with
      low spinal mineral density at L2-4. T-11 and T-12 were the vertebrae most
      frequently deformed (wedge angle exceeding mean +/- 3 SD in a group of 50 young
      healthy women, 25-45 years old). The distribution of deformed vertebrae was found
      to be significantly different from those qualified as "fractured" according to
      Kleerekoper et al.'s (1984) and Melton et al.'s (1989) criteria. The overall
      information afforded by past and present data indicates that in postmenopausal
      women, vertebral deformation may occur with the help of mechanical solicitations
      plus high bone remodeling rates, as well as by structural collapse (fracture).
      The information obtained does not allow one to quantify the relative contribution
      of each set of factors to the wedging phenomenon.

PMID- 8541137
TI  - Dual X-ray absorptiometry--cross-calibration and normative reference ranges for
      the spine: results of a European Community Concerted Action.
AB  - Bone density measurements by dual X-ray absorptiometry (DXA) of the spine can now
      be made precisely, but there is no uniformity in reporting results and in
      presenting reference data. A European Union Concerted Action therefore devised a
      uniform procedure for cross-calibrating and standardizing instruments, using the
      European spine phantom (ESP) prototype. This phantom differs in a number of
      respects from the final version of the ESP. Eighteen centers in nine countries
      obtained 1619 records (1035 women) from Caucasian subjects, aged 20-80 years,
      drawn from normal populations. The DXA machines used were made by the Hologic,
      Lunar, and Norland companies. Highly statistically significant differences were
      evident between populations, both in apparent rates of bone loss with age and in
      the spread of values about the age-adjusted means. There were small residual
      differences in the results obtained with the three machine brands which could
      have been due to the relatively large between-center population differences we
      observed. The alternative or additional explanation that they were attributable,
      in part, to the design differences between the ESP prototype and the definitive
      ESP, which became available after this study was completed, was shown to be a
      valid possibility. Results from postmenopausal women reported in relation to the
      years that have elapsed since menopause showed reduced population variance when
      compared with conventional reporting in relation to age. After cross-calibration,
      the center with the highest age-adjusted normal density value averaged 23% more
      than the center with the lowest. It is therefore crucially important to select
      appropriate reference data in clinical and epidemiological studies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8541138
TI  - The synthesis of collagenase, gelatinase-A (72 kDa) and -B (95 kDa), and TIMP-1
      and -2 by human osteoblasts from normal and arthritic bone.
AB  - Bone resorption is a complex multistep process that involves removal of both the
      organic and mineral constituents of bone matrix by proteolytic enzymes
      synthesized by osteoblasts and osteoclasts. To further understand the role of
      matrix metalloproteinases (MMPs) and their specific inhibitors TIMPs (tissue
      inhibitor of metalloproteinases) in this process, human osteoblasts were obtained
      by sequential enzymatic digestion from samples of bone from normal donors and
      patients with various forms of arthritis; first passage cells were used in all
      experiments and cultured on a type I collagen substratum. Collagenase was
      detected by an ELISA in supernatants from unstimulated osteoblasts (range 12-730
      ng/mL), although the levels did not appear to bear any relationship to the age or
      clinical status of the patient; treatment with parathyroid hormone (PTH; 2
      units/mL) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3, 10 ng/mL] had no added
      effect, but mononuclear cell conditioned medium (MCM; 5% v/v) and interleukin-1
      alpha (IL-1 alpha; 1 ng/mL) both stimulated collagenase synthesis, in the case of
      MCM by two orders of magnitude. TIMP-1 was detected in unstimulated cultures by
      an ELISA (range 320-590 ng/mL), the mean level being three-fold greater than for
      collagenase and was stimulated by 1,25(OH)2D3 and MCM treatment. Degradation
      studies showed that, over a 120 h culture period, one third of the collagen
      substratum was degraded by unstimulated cells. PTH and 1,25(OH)2D3 had no effect
      on this endogenous level of lysis, but addition of MCM and IL-1 alpha resulted in
      a significant increase in collagen degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541139
TI  - The bone mineral content of weight-bearing bones is influenced by the ratio of
      sitting to standing height in elderly Gambian women.
AB  - Body size is an important predictor of bone mineral content (BMC) at various
      anatomical sites but the influence of relative body proportions on BMC has
      previously been little studied. Using single- and dual-photon absorptiometry, we
      measured BMC at the distal and midshaft of the radius, the neck of femur, and the
      lumbar spine in 190 rural West African women aged 45-84 years. After regression
      adjustment for age, bone width and weight, sitting height and standing height
      were not separate significant determinants of BMC, except at the lumbar spine
      (standing height, p < 0.05). However, the ratio of sitting:standing height was a
      significant determinant of BMC at the neck of femur and lumbar spine, but not the
      midshaft or distal radius. The fact that sitting:standing height ratio is a
      positive predictor for BMC at hip and lumbar spine may reflect a higher peak bone
      mass or selective conservation of mineral in weight-bearing bones in subjects
      with a proportionately longer torso. We do not know whether the relationship is
      racially determined but we recommend that this simple combination of measurements
      be used in further studies in subjects of all races.

PMID- 8541140
TI  - The effects of androgens on the mechanical properties of primate bone.
AB  - Feral adult female cynomolgus monkeys were divided into three groups and treated
      for two years: (1) normal controls; (2) weak androgenic treatment
      (androstenedione+estrone); and (3) strong androgenic treatment (testosterone).
      The tibiae and the trabecular bone of femoral head from each group were tested
      mechanically. There were no significant changes in the elastic modulus and shear
      modulus of the tibiae, measured by three point bending and torsion tests, among
      the three groups. Significant increases in energy absorption capacity (+45% for
      testosterone) and maximum shear stress (+19.4% for androstenedione and +39% for
      testosterone) of the tibiae, measured by torsion tests, and the cortical bone
      density (+5.5% for androstenedione and +8.7% for testosterone), were observed.
      Testosterone treatment significantly increased torsional rigidity (+23%) and
      bending stiffness (+15%) of the tibiae while androstenedione did not change any
      of these structural properties. The results of compression tests of the
      trabecular bone samples indicated significant increases in their elastic modulus
      after androstenedione (+88%) or testosterone (+107%) treatment. The maximum
      compressive stress of the testosterone treated samples was significantly higher
      than those of both normal (+28%) and androstenedione treated groups (+26%). The
      trabecular bone density increased after both androgenic treatments. This increase
      was significant for the testosterone treated group (+8.6%). We conclude that in
      the young cynomolgus monkey, long-term androgenic treatment significantly
      improves some of the mechanical properties of both cortical and trabecular bones,
      increases bone density, and the stronger the androgen, likely, the more
      pronounced is the effect.

PMID- 8541141
TI  - Effect of abnormal mineralization on the mechanical behavior of X-linked
      hypophosphatemic mice femora.
AB  - The Hyp mouse is an established animal model of X-linked hypophosphatemia, one of
      the most common genetic forms of metabolic bone disease in humans. This study
      describes the first determination of whole bone mechanical behavior in the
      heterozygous male and female Hyp mouse. Femora from 12-week-old mice were tested
      in torsion. The contribution of structural and material properties to mechanical
      behavior was determined by geometrical evaluation prior to testing and by
      analysis of the diaphyseal mineral after testing. The male and female Hyp femora
      were found to undergo significantly more angular deformation at failure than the
      same sex normal femora (82.49 +/- 24.37 vs. 22.63 +/- 8.02 rad/m [corrected] for
      the females and 128.90 +/- 37.05 vs. 22.79 +/- 7.24 rad/m [corrected] for the
      males) and to have a significantly lower structural stiffness (0.373 +/- 0.130 x
      10(-3) vs. 1.33 +/- 0.380 x 10(-3) [corrected]  [N-m/(rad/m)] for the females and
      0.167 +/- 0.104 x 10(-3) vs. 1.60 +/- 0.502 x 10(-3) [corrected] [N-m/(rad/m)]
      for the males). The male Hyp femora had a significantly lower failure torque than
      male normal femora (1.58 +/- 0.62 x 10(-2) vs. 3.44 +/- 1.57 x 10(-2) N-m).
      Because the polar movement of inertia, a geometrical property that affects
      torsional behavior, was not significantly different between the Hyp femora and
      the same sex normals, differences in mechanical behavior were attributed to
      material properties.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541143
TI  - Human vertebral cancellous bone surface distribution.
AB  - The three-dimensional distribution of bone surface and the bone volume fraction
      (BV/TV) of 110 human vertebral cancellous bone specimens from seven individuals
      were measured using a three-dimensional radiographic method (microcomputed
      tomography). The ratios of the three principal projections of bone surface per
      total volume were found to be relatively constant for specimens examined in this
      study. The constancy of the projected surface ratios means that the fraction of
      the total bone surface oriented in any direction does not change markedly with
      BV/TV. Bone volume fraction was a good predictor of bone surface per total volume
      (BS/TV) for a one-parameter nonlinear model (r2 = 0.92). The results of this
      pilot study suggest that the changes in surface distribution which occur during
      age-related bone loss are largely predetermined rather than adaptive. The results
      are also consistent with the idea that cancellous bone tends to maintain a
      constant ratio of trabecular number for the principal directions. If these
      inferences from the data are correct, the morphogenetic processes which create
      the initial adult trabecular pattern become of primary interest. A model was
      developed which explained the strong relationship between BS/TV and BV/TV. The
      model was used to demonstrate the importance of morphogenetic processes.

PMID- 8541142
TI  - Regulators of chondrocyte differentiation in tibial dyschondroplasia: an in vivo
      and in vitro study.
AB  - Tibial dyschondroplasia (TD) is a disorder of endochondral bone growth and
      results in the retention of a mass of unmineralized, avascular cartilage
      extending into the metaphysis. We have studied various parameters of chondrocyte
      differentiation, both in isolated chick chondrocytes and growth plate sections,
      in an attempt to determine whether the inhibition in chondrocyte differentiation
      seen in TD is a consequence of an inherent incapability of chondrocytes to
      differentiate terminally and mineralize. Results from in vitro experiments
      indicated that both normal and lesion chondrocytes synthesized a matrix that
      stained with antibodies to types II and X collagen and displayed foci of
      mineralization. Alkaline phosphatase activity in lesion chondrocytes was
      significantly increased in comparison to that in normal hypertrophic
      chondrocytes. In addition, normal and lesion chondrocytes in culture synthesized
      transforming growth factor-beta and 24,25(OH)2D3 but not 1,25(OH)2D3. There was
      no significant difference in the production rate of these growth regulators
      between normal and lesion chondrocytes. In contrast, in growth plate sections,
      alkaline phosphatase activity was markedly reduced in the lesion chondrocytes and
      sites of mineralization were not evident. Type II collagen was located throughout
      the growth plate and lesion, but type X collagen was not present within the
      lesion except at sites of vascularization. These results indicate that, in
      culture, lesion chondrocytes have the ability to differentiate terminally and
      mineralize, and suggest that the primary abnormality in TD is related to a
      developmental fault which is only operative in vivo. This may include a defect in
      cartilage vascularization and/or impairment of chondrocyte differentiation by
      mechanisms that have not yet been elucidated but may involve the abnormal
      production of regulatory factors.

PMID- 8541144
TI  - Ontogenesis of chondro/osteoclasts and their precursors in the mandibular condyle
      of the mouse.
AB  - Tartrate-resistant acid phosphatase (TRAP) histochemistry has been used to follow
      chondro/osteoclasts and their precursors during ontogenesis of the mandibular
      condyle of the mouse (from day 16 of gestation until day 15 of neonatal life).
      TRAP+ mono-, bi-, and multinuclear cells were counted separately in the
      perichondrium, along the resorption front and in the subchondral spongiosa. Index
      of cellular density was calculated by dividing the absolute numbers of cells by
      the length of resorption front or the area of spongiosa, respectively. The study
      revealed that TRAP+ cells are present in the perichondrium of the mandibular
      condylar cartilage from the first day of its existence as an organ, namely day 17
      of gestation. These cells are more numerous in the posterior part of the condyle,
      and reach their maximal number on the third day of neonatal life. Along the
      resorption front, mono-, bi-, and multinucleated TRAP+ cells were counted. Their
      total number and their respective indexes of cellular density changed variably
      during the observation period: (a) the number of mononuclear cells increased
      gradually and, by the end of the observation period, was 13 times greater than it
      was at the beginning; (b) the number of binuclear cells increased threefold; and
      (c) the number of multinuclear cells stayed constant, except for a small peak
      around the time of birth. The changes in the spongiosa showed an opposite trend.
      In the spongiosa, the index of cellular density of the mononuclear TRAP+ cells
      increased slightly during ontogenesis. The number of binuclear cells increased
      twofold, while the number of multinuclear cells increased 17-fold.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8541145
TI  - 22-Oxacalcitriol does not interfere with parathyroid hormone-induced phosphaturia
      or cyclic-AMP excretion.
AB  - The vitamin D analogue, 22-oxacalcitriol [22-oxa-1,25(OH)2 vitamin D3], has
      pleiotropic effects similar to or greater than calcitriol but has markedly fewer
      calcemic and phosphatemic effects. To test the hypothesis that the lesser
      phosphatemic effect of 22-oxacalcitriol is due, at least in part, to a lack of
      interference with the phosphaturic effect of parathyroid hormone, acute clearance
      experiments were performed in parathyroidectomized rats receiving continuous 1-34
      parathyroid hormone (PTH) infusion together with 22-oxacalcitriol (200 pmol.100 g
      body weight-1.min-1) or vehicle. In contrast to the previously reported
      inhibitory effect of calcitriol on PTH-induced phosphaturia, fractional excretion
      of phosphorus increased similarly in both groups, from 0.05 +/- 0.01 to 0.26 +/-
      0.02 (p < 0.01) in the vehicle-infused animals and from 0.04 +/- 0.01 to 0.24 +/-
      0.02 (p < 0.01) in the 22-oxacalcitriol-treated rats (p between groups not
      significant [n.s.]). Urinary cyclic AMP excretion also increased similarly, from
      45.5 +/- 5.2 to 101.6 +/- 21.6 (p < 0.01) and from 45.4 +/- 5.6 to 102.6 +/- 16.7
      pmol/min (p < 0.01), respectively (p between groups n.s.). In search for a
      nongenomic mechanism that might account for the disparate effects of 22
      oxacalcitriol and calcitriol, OK cells, which are reminiscent of the mammalian
      proximal tubule cell, were stimulated with calcitriol and 22-oxacalcitriol and
      free intracellular calcium concentration was determined. At high concentrations,
      calcitriol caused a dose-dependent increase in [Ca2+]i; 22-oxacalcitriol had no
      effect on [Ca2+]i at any concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541146
TI  - Differentiation of MC3T3-E1 osteoblasts is associated with temporal changes in
      the expression of IGF-I and IGFBPs.
AB  - We examined the relationship between osteoblast maturation and temporal changes
      in the secretion of IGF-I and the IGF-binding proteins (IGFBPs) in the MC3T3-E1
      model of osteoblast development. IGF-I was present at low levels in conditioned
      media in proliferating preosteoblasts (3.7 +/- 1.7 ng/micrograms DNA and 3.9 +/-
      0.6 at culture (days 3 and 9) and increased progressively in postmitotic
      differentiating osteoblasts, reaching a maximal concentration of 13.1 +/- 1.5
      ng/micrograms DNA by day 25 of culture. We also observed an increase in IGF-I
      mRNA expression. Using Western ligand blot and immunoblot techniques, we found
      that IGFBP-2, -4, and -5 also displayed temporal differences in expression during
      MC3T3-E1 development. We observed a sustained increase in IGFBP-2, -4, and -5
      mRNA expression between days 10-14, coincident with the onset of differentiation.
      IGFBP-2 and IGFBP-4 protein concentrations increased in parallel with IGFBP mRNA
      expression, but IGFBP-5 levels peaked between days 8-14 of culture, and declined
      thereafter in spite of persistent IGFBP-5 mRNA levels. These findings suggest
      complex transcriptional and post-transcriptional regulation of IGFBP metabolism
      during osteoblast development. Thus, IGF-I and IGFBP production are regulated
      during osteoblast development. In turn, time-dependent changes in IGF-I and
      modulation of IGF-I bioavailability by IGFBPs may regulate the osteoblastic
      developmental sequence.

PMID- 8541147
TI  - The use of stable tracers to study intestinal calcium absorption. The Italian
      Society of Osteoporosis.
AB  - This paper represents the final document released by the Italian Society of
      Osteoporosis (S.I.OP.), on the occasion of its fifth annual meeting held in
      Padova, Italy (November 30-December 3, 1993). The S.I.OP. has in fact planned to
      periodically organize a conference on still-debated, controversial issues. After
      an exhaustive discussion of the various aspects of the problem by qualified
      experts in the field, a solution will be proposed by the members of the Society.
      The problems related to the use of radioactive tracers to study intestinal
      calcium absorption and the possible ways to over-come them were the issues
      discussed last year, by four panelists (R. P. Heaney, C. Gennari, G. Mioni, and
      S. Minisola) coordinated by G. F. Mazzuoli.

PMID- 8541148
TI  - The Bone and Tooth Society spring meeting. Warwick, United Kingdom, March 27,
      1995. Abstracts.

PMID- 8541149
TI  - Coenzyme Q10 and periodontal disease.

PMID- 8541150
TI  - Porcelain veneers: the effects of contaminants and cleaning regimens on the bond
      strength of porcelain to composite.
AB  - An in-vitro study was carried out to investigate the effects of contamination of
      the porcelain surface on the shear-bond strength of a dual-cure composite luting
      cement to etched, silanated porcelain. Furthermore, the effects of different
      cleaning regimens were studied. A total of 390 etched, silanated porcelain
      specimens were randomly divided into 13 groups of 30. Shear-bond strengths were
      measured for a control group and for specimens contaminated with saliva, die
      stone, and latex gloves. Freshly contaminated samples were subject to three
      cleaning regiments; water wash and dry, cleansing with acetone, and cleansing
      with 37% phosphoric acid gel. Bond strengths to the cleansed surfaces were
      measured. Weibull analysis and analysis of variance were applied to the results.
      Saliva and latex glove contamination did not significantly affect shear-bond
      strength. Die stone contamination markedly reduced the bond strength and cleaning
      did not restore the bond strength for these specimens. Contact between porcelain
      veneers and stone models should therefore be avoided. The wash/dry and phosphoric
      acid cleaning regimens did not significantly improve or reduce bond strengths for
      contaminated specimens. Acetone cleaning produced a marked reduction in bond
      strength under all experimental conditions and should not be used.

PMID- 8541151
TI  - Professional attitudes to specialisation and minor oral surgery in general dental
      practice.
AB  - A questionnaire was distributed to the general dental practitioners of Grampian
      Region to investigate their perception of the need, the advantages and
      disadvantages, qualifications and location, of a 'specialist' or 'specialist'
      practice in minor oral surgery. A 92% response rate was achieved. Nearly nine out
      of ten practitioners believed there was a need for such a 'specialist' with 85%
      being willing to refer to one. Up to 48% would refer more patients for minor oral
      surgery than they do at present. They envisaged reduced patient waiting and
      improved convenience as the main advantages of such a service. The patient paying
      for treatment and post-operative complications are perceived as the major
      disadvantages. The type of procedures that the practitioners expect a
      'specialist' to undertake is as expected, although only 75% expect implants to be
      undertaken. Most practitioners, 86%, would prefer if the 'specialist' worked in a
      'specialist' only practice. Other alternative venues would be viewed favourably
      with the 'specialist' working in another dental practice being the least
      favourable. Nearly nine out of ten practitioners believe that a qualification is
      necessary for such a 'specialist' and if a minor oral surgery qualification was
      introduced 73% of practitioners would regard it as the most appropriate
      qualification. Many practitioners in principle would attempt to gain it, 82% of
      practitioners would refer their private patient to a specialist with this
      qualification.

PMID- 8541152
TI  - Operative and microbiological validation of visual, radiographic and electronic
      diagnosis of occlusal caries in non-cavitated teeth judged to be in need of
      operative care.
AB  - The diagnosis of occlusal caries depends upon the correct identification of
      demineralised enamel and dentine. However, tissue demineralisation precedes
      bacterial infection so that dentine may be demineralised but uninfected. The
      presence of a bacterial infection of dentine may be a more relevant factor to be
      considered when planning to restore a carious lesion. The aim of this clinical
      study was to validate three techniques for the diagnosis of occlusal caries as
      demineralised tissue and as infected demineralised tissue during cavity
      preparation. The study sample was 82 non-cavitated occlusal lesions, judged by
      various dentists to be in need of operative care. The diagnostic techniques used
      by the single operator were vision, bitewing radiography and electronic caries
      diagnosis. The validating techniques were a caries detector dye to stain
      demineralised tissue, microbiological sampling to determine the level of
      infection of the dentine and clinical assessment of the dentine at operation. The
      caries detector dye showed demineralised dentine in 96% of the referred lesions.
      This demineralisation was reliably predicted by the electronic readings. However,
      the dentine samples from many teeth yielded only small numbers of bacteria
      indicating no, or only a very low level of bacterial infection. Neither vision
      nor electronic readings reliably predict heavily infected dentine. Radiographic
      evidence of dentine demineralisation was significantly associated with heavily
      infected dentine and this dentine was soft and wet at operation.

PMID- 8541153
TI  - Day case oral surgery: a review of 25 years experience at the Dublin Dental
      Hospital.
AB  - A retrospective analysis of the changing work-load at the Dublin Dental Hospital
      oral surgery day case unit was undertaken. This involved 26,697 operations
      performed during the 25-year period 1968-1992. The results show how the practice
      of oral surgery has changed over this time. Annual totals ranged from 766 to 1549
      operations. While most categories of operations remained largely unchanged, the
      removal of impacted third molars increased from 10.5% of the annual total to
      57.0%. Routine extractions of permanent teeth decreased from 53.9% of the annual
      total to 18.0%.

PMID- 8541154
TI  - World War II: the Army Dental Corps in the Far East.
AB  - During the recent remembrance of VJ day, war veterans have related their own
      experiences as prisoners in the Japanese PoW camps. In this article, members of
      The Army Dental Corps recount their own histories during the war in the Far East.
      Whilst the conditions in which they lived are horrifying, the ingenious creation
      of dental tools and chairs from what materials they could find in order to carry
      on performing what they were enlisted to do--dentistry--is inspiring to say the
      least.

PMID- 8541155
TI  - Evaluating quality through records and radiographs--a rationale for general
      dental practice.
AB  - Patients need not necessarily be directly involved in quality assurance
      procedures. Well-structured records and good quality radiographs can provide a
      vehicle for both examining and carrying out audit of the process of care. Minimum
      disruption of practice procedures and on-going patient care will result.

PMID- 8541156
TI  - Well, not exactly.

PMID- 8541157
TI  - Preconditioning: a balanced perspective.

PMID- 8541158
TI  - Should balloon angioplasty be used instead of surgery for native aortic
      coarctation?

PMID- 8541159
TI  - von Willebrand factor and its relevance to cardiovascular disorders.
AB  - In the past decade the importance of the vascular endothelium in cardiovascular
      pathophysiology has become more apparent. One substance that is synthesised by
      and stored in endothelial cells is von Willebrand factor (vWF). When released,
      vWF seems to mediate platelet aggregation and adhesion to the vascular
      endothelium. Because the release of vWF is increased when endothelial cells are
      damaged, vWF has been proposed as an indicator of endothelial disturbance or
      dysfunction. The availability of such an index of endothelial dysfunction may
      have clinical value, because measurement of such a marker can be a non-invasive
      way of assisting in diagnosis or as an indicator of disease progression. The
      known association between vWF, thrombogenesis, and atherosclerotic vascular
      disease also suggests that high concentrations of vWF may be an indirect
      indicator of atherosclerosis and/or thrombosis. In addition, high vWF
      concentrations have prognostic implications in patients with ischaemic heart
      disease and peripheral vascular disease.

PMID- 8541160
TI  - Angiotensin converting enzyme gene deletion allele is independently and strongly
      associated with coronary atherosclerosis and myocardial infarction.
AB  - OBJECTIVE: To investigate the association of the three angiotensin converting
      enzyme (ACE) genotypes, DD, ID, and II, with the occurrence or absence of
      coronary atherosclerosis and with myocardial infarction and hypertension. DESIGN:
      Cohort analysis study. SETTING: North-Italy reference centre. SUBJECTS: 388 white
      Italian patients (281 males; mean age 60.7 (SD 12.5) years) with proven coronary
      atherosclerosis (n = 255) or with angiographically normal coronary arteries (n =
      133). A further group of 290 healthy blood donors was tested for allele frequency
      comparison. INTERVENTIONS: ACE/ID polymorphism was analysed with polymerase chain
      reaction on DNA from white blood cells. MAIN OUTCOME MEASURES: Coronary
      atherosclerosis, myocardial infarction, hypertension. RESULTS: The D and I allele
      frequencies were respectively 0.63 and 0.37 in the overall healthy blood donor
      group and 0.66 and 0.34 in the overall study group. In the latter, univariate
      analysis showed (1) that coronary atherosclerosis (255 patients) was associated
      with the deletion allele, with an odds ratio (OR) of 5.78 for DD/II, P < 0.001,
      and 2.39 for ID/II, P = 0.006; and (2) that myocardial infarction (154 patients)
      was associated with the DD genotype (OR DD/II = 2.56, P = 0.007), but not with
      the ID genotype (OR DD/II = 1.96, P = 0.056). Finally, hypertension proved to be
      unrelated with the ACE genotype. The distribution between the three genotypes of
      known risk factors for coronary artery disease was similar. Logistic regression
      modelling, performed to test the association of the selected risk factors
      simultaneously with coronary atherosclerosis and myocardial infarction, showed
      that the deletion allele (whether DD or ID) was the strongest risk factor for
      atherosclerosis, and that the D allele was significantly associated with the risk
      of infarction (although to a lesser extent than with coronary atherosclerosis).
      CONCLUSION: ACE deletion polymorphism is strongly and independently associated
      with coronary atherosclerosis and, to a lesser extent, with myocardial
      infarction. As such, the results are analogous to what has already been reported
      in French white, Japanese, and Welsh coronary patients.

PMID- 8541161
TI  - Can early closure and restenosis after endoluminal stenting be predicted from
      clinical, procedural, and angiographic variables at the time of intervention?
AB  - OBJECTIVES: To develop a statistical model to assess the risk of early closure
      and restenosis on the basis of the information available at the time of stent
      implantation. DESIGN: An exploratory forward, stepwise multivariate logistic
      regression for each adverse event and multivariate polychotomous analysis for
      both events. SETTING: Tertiary referral centre for interventional treatment of
      coronary artery disease. PATIENTS: 243 consecutive, successful stenting
      procedures between 1986 and 1993 with the Wallstent, the Palmaz-Schatz and Wiktor
      stents with analysis of clinical, procedural, and angiographic variables. MEAN
      OUTCOME MEASURES: Early closure was defined as angiographically documented stent
      thrombosis within the first 3 weeks after implantation and restenosis according
      to the 50% reference diameter reduction criterion. RESULTS: Overall early closure
      and restenosis rates were 14.4% (35/243) and 19.2% (40/208, for a 97% repeat
      angiography rate). The statistical model predicted a worse outcome for male
      patients, with less restenosis in female patients. The only risk factor in female
      patients was the presence of collaterals to the target lesion. For male patients
      the following risk factors for closure and restenosis were retained: multiple
      stent implantation during the same session, the presence of collaterals to the
      target lesion, stenting of the left anterior descending artery or of the left
      circumflex artery, and bailout stenting. Only bailout stenting implied a
      decreased restenosis risk. CONCLUSIONS: Clinical, procedural and angiographic
      variables increase the risk for early closure and restenosis after endoluminal
      stenting. The prediction models described above need to be validated
      prospectively.

PMID- 8541163
TI  - Prospective study of patients aged 55 years or less with acute myocardial
      infarction between 1981 and 1985: outcome 7 years and beyond.
AB  - OBJECTIVE: To determine the long-term prognosis of patients after a myocardial
      infarction (MI) at a young age. DESIGN: Prospective cohort study of patients aged
      55 years or less suffering a myocardial infarction. SETTING: A single coronary
      care unit admitting patients from the community. PATIENTS: 255 consecutive
      patients (210 men) aged 55 years or less admitted between 1981 and 1985 after
      acute MI. Twenty four patients died in hospital or within 3 months of infarction
      and 11 were lost to further follow up after discharge. Of the remaining patients,
      150 (mean (SD) age 48 (5.7) years) able to exercise 3 weeks after infarction and
      who agreed to undergo coronary angiography were recruited to a study group and
      seen 18 months, and 3, 5, and 7 years after MI. In addition, a cross sectional
      analysis of survival was made to a median of 120 months. Seventy 3 month
      survivors (mean (SD) age 48 (5.8) years) were not recruited to the study group
      but were traced for late survival through their general practitioners and family
      health service associations to a median of 130 months. MAIN OUTCOME MEASURES:
      Survival in young patients after MI and the survival of 3 month survivors
      stratified by their ability to exercise and agreement to undergo angiography. The
      rate of coronary artery surgery (CAGB) and reinfarction during the first 7 years
      after index MI in patients recruited to the study group. RESULTS: Sixteen
      patients (6%) died in hospital and eight (3%) within 3 months of the index
      infarction. The 7 and 11 year survival rates in the whole cohort of 255 patients
      were 80% and 66% respectively using life table methods. Survival 7 years after
      MI, in patients recruited to the study group was better than in those not
      recruited (93% v 79%, P = 0.001), but thereafter mortality in the study group
      accelerated and there was no significant difference in survival 11 years after
      infarction (76% v 67%, P = 0.05). There was a trend towards higher mortality in
      patients with multivessel disease and severely impaired left ventricular
      function. During the first 7 years after MI, 38 of 150 patients in the study
      group underwent CABG and 19 suffered reinfarction, which was fatal in three.
      CONCLUSION: The medium-term prognosis of young survivors of MI is good,
      particularly in patients recruited to the study group. After 7 years there is an
      increase in mortality and the long-term prognosis is less favourable. This should
      be taken into account when planning future management and follow up of young
      patients after MI.

PMID- 8541162
TI  - Autoimmunity to alpha myosin in a subset of patients with idiopathic dilated
      cardiomyopathy.
AB  - OBJECTIVE: To use an enzyme linked immunoassay (ELISA) technique to assess
      frequency and disease specificity of anti-alpha-myosin antibodies in patients
      with dilated cardiomyopathy and their relatives. METHODS: Evaluation was
      performed on sera (dilution 1/320) from 123 consecutive patients with dilated
      cardiomyopathy (WHO criteria) (age 42 (SD 14) years), 252 of their relatives (35
      (17) years), 203 healthy controls (45 (16) years), and 92 patients with ischaemic
      heart disease (63 (11) years). RESULTS: Abnormal antibody levels were commoner in
      patients with dilated cardiomyopathy (25, 20%) than in ischaemic heart disease
      (4, 4%), or normal controls (4, 2%, P = 0.001). Forty one (16%) of the relatives
      had abnormal results compared to the controls (4, 2%, P < 0.001) and antibodies
      were detected in 20 (38%) of pedigrees. Relatives from non-familial kindreds had
      higher antibody levels than those with familial disease (P << 0.001), and higher
      antibody levels were identified in 53 relatives of probands who had abnormal
      results compared to 116 relatives for whom the proband had a normal result (0.37
      (SEM 0.02) v 0.22 (0.01); P < 0.001). CONCLUSIONS: The finding of anti-alpha
      myosin antibodies in 20% of patients with dilated cardiomyopathy, in 16% of their
      asymptomatic relatives, and in 38% of families (particularly those with non
      familial disease and where proband also had an abnormal result) provides
      additional evidence for autoimmunity against alpha myosin in a subset of
      patients.

PMID- 8541164
TI  - Clinical significance of inferior ST elevation during acute anterior myocardial
      infarction.
AB  - OBJECTIVES: To clarify the genesis and clinical significance of inferior ST
      elevation during acute anterior myocardial infarction. PATIENTS AND DESIGN: A
      total of 106 patients with first acute anterior myocardial infarction (< or = 6
      h) were divided into two groups according to the presence (group A, n = 12) or
      absence (group B, n = 94) of ST elevation of > or = 1 mm in at least two of the
      inferior leads on the admission electrocardiogram. RESULTS: On admission
      electrocardiograms, group A had a smaller summed ST deviation in the lateral limb
      leads than group B. On emergency coronary arteriograms, the incidence of a
      wrapped left anterior descending artery was higher in group A than in group B
      (100% v 27%, P < 0.01). The incidence of occlusion of a left anterior descending
      artery distal to its first diagonal branch was higher in group A than in group B
      (100% v 46%, P < 0.01). Peak serum creatine kinase activity and in-hospital
      mortality tended to be lower in group A than in group B. Group A had better left
      ventricular ejection fraction and regional wall motion in the anterobasal and
      anterolateral regions in the chronic phase than group B. In contrast, regional
      wall motion in the diaphragmatic region was reduced to a greater extent in group
      A than in group B. CONCLUSIONS: Inferior ST elevation during acute anterior
      myocardial infarction appears only in the presence of a combination of a lesser
      degree of transmural ischaemic myocardium in the anterobasal and anterolateral
      wall together with transmural ischaemic myocardium in the inferior wall; in all
      cases there was occlusion of a wrapped left anterior descending artery distal to
      its first diagonal branch. Patients with such an ST elevation appear to have a
      better in-hospital prognosis than those without it.

PMID- 8541165
TI  - Initial and subsequent angiographic outcome of percutaneous transluminal
      angioplasty performed on internal mammary artery grafts.
AB  - OBJECTIVE: To estimate the initial outcome and incidence of restenosis of
      angioplasty of internal mammary artery grafts in a retrospective study. METHODS:
      The study population consisted of 46 patients (48 lesions) who underwent first
      balloon angioplasty within the internal mammary artery graft. Most (37/48) were
      at the distal anastomosis. A few (8/48) were in the graft body. Six patients with
      the evidence of angiographic restenosis underwent a second angioplasty. RESULTS:
      The success rate and the restenosis rate of the first angioplasty was 73% and 30%
      respectively. Of the 34 patients (35 lesions) with a successful first
      angioplasty, 30 underwent follow up angiography with a restenosis rate of 30%
      (9/30). A second angioplasty was performed on six of the nine restenotic lesions,
      with a success rate of 83% and no restenoses. The percent diameter stenosis of
      the recipient native coronary artery was significantly greater in the restenosis
      group, at 75 (SD 27)% v 89 (17)%, p < 0.05. CONCLUSIONS: First angioplasty of 46
      patients (48 lesions) within an internal mammary artery graft was performed with
      a success rate of 73% and a restenosis rate of 30% (follow up rate of 88%). The
      extent of the stenosis of the recipient native coronary artery may affect the
      restenosis rate.

PMID- 8541166
TI  - Concentration of circulating plasma endothelin in patients with angina and normal
      coronary angiograms.
AB  - BACKGROUND: Some patients with angina pectoris and normal coronary arteriograms
      have reduced coronary flow reserve and abnormal endothelium dependent vasodilator
      responses. Endothelin-1 (ET-1), a potent vasoconstrictor, is an important
      modulator of microvascular function and may also have algogenic properties.
      METHOD: Plasma ET-1 was measured in peripheral venous blood in 40 patients (30
      women) (mean (SD) age 56 (8) years) with angina and normal coronary arteriograms
      and 21 normal controls (17 women) (mean (SD) age 53 (7) years). Patients with
      systemic hypertension, left ventricular hypertrophy, or coronary spasm were
      excluded. Plasma ET-1 was measured using radioimmunoassay. RESULTS: Thirty five
      patients had > or = 1 mm ST segment depression during exercise. Left bundle
      branch block was present in four patients at rest and in one during exercise.
      Mean (SD) (range) concentration of ET-1 (pg/ml) was higher in patients than in
      controls (3.84 (1.25) (1.97-7.42) v 2.88 (0.71) (1.57-4.48) P < 0.0001). In
      patients with "high" (> control mean (one SD)) ET-1 concentrations (n = 23), the
      time to onset of chest pain during exercise was significantly shorter (6.21 (3.9)
      v 9.03 (3.9) min; p = 0.01) than in patients with "low" ET-1 concentrations. Of
      the five patients with left bundle branch block, four had plasma ET-1
      concentration > 4.0 pg/ml. CONCLUSION: Plasma endothelin is raised in patients
      with angina and normal coronary arteriograms and is consistent with the
      demonstration of endothelial dysfunction in such patients. The association
      between "high" plasma ET-1 and an earlier onset of chest pain during exercise
      suggests that endothelin may also have a role in the genesis of chest pain in
      patients with normal coronary arteries.

PMID- 8541168
TI  - Interaction of ischaemia and encainide/flecainide treatment: a proposed mechanism
      for the increased mortality in CAST I.
AB  - OBJECTIVE: To determine whether an interaction between encainide or flecainide
      and intercurrent ischaemia could account for the observed increase in cardiac and
      sudden deaths in the study group in the Cardiac Arrhythmia Suppression Trial
      (CAST) I. DESIGN: CAST I was a randomised, double blind, placebo controlled study
      in which patients received the drug which suppressed at least 6 premature
      ventricular contractions per minute by 80% or episodes of non-sustained
      ventricular tachycardia by 90%. Arrhythmic sudden death or aborted sudden death
      were the study end points. Measured secondary end points included recurrent
      myocardial infarction, new or increasing angina pectoris, congestive heart
      failure, and syncope. The CAST I database was analysed to determine which of
      three end points occurred first--cardiac death or cardiac arrest, angina
      pectoris, or non-fatal recurrent infarction. They were regarded as mutually
      exclusive end points. The triad of cardiac or sudden arrhythmic death plus
      congestive heart failure and syncope was similarly analysed. RESULTS: It was
      assumed that recurrent non-fatal infarction and new or increasing angina pectoris
      were ischaemic in origin. The sum of these non-fatal ischaemic end points and
      sudden death were nearly identical in the placebo group (N = 129) and the
      treatment group (N = 131). The one year event rate in each group was 21%.
      However, the treatment group had a much greater fatality rate (55 v 17; P <
      0.0001) than the placebo group. The same relation was found when the data were
      examined on the basis of drug exposure rather than intention to treat. The
      temporal and circadian events were similar in each group and were consistent with
      an ischaemic pattern. No such patterns emerged from analysis of the presumed non
      ischaemic end points of congestive heart failure and syncope. CONCLUSIONS: These
      data suggest that the interaction between active ischaemia and treatment with
      encainide or flecainide may have been responsible for the increased mortality
      seen in the treatment group in CAST I. This conversion of a non-fatal to a fatal
      event emphasises the need for future antiarrhythmic drugs to be screened in
      ischaemic models.

PMID- 8541167
TI  - Plasma mediated neutrophil stimulation during coronary angioplasty: autocrine
      effect of platelet activating factor.
AB  - BACKGROUND: Polymorphonuclear neutrophils are involved in the development of
      myocardial injury during ischaemia and reperfusion. Coronary angioplasty has been
      shown to result in neutrophil activation. This may be a result of contact with
      ligands expressed by endothelial cells or response to soluble stimuli released
      from ischaemic tissue into the plasma or both. OBJECTIVE: To investigate plasma
      mediated neutrophil activation during angioplasty. METHODS AND RESULTS: Plasma
      samples were collected from the coronary sinus, femoral artery, and femoral vein
      of 14 patients undergoing angioplasty, before and after the first balloon
      inflation and at the end of the procedure. Plasma samples were incubated with
      washed neutrophils isolated from healthy donors. Expression of the adhesion
      molecules CD18 integrin and L-selectin (Leu-8) was measured by flow cytometry,
      and superoxide anion production was measured by chemiluminescence. Plasma samples
      from the coronary sinus and femoral artery but not from the peripheral vein
      induced increased expression of neutrophil CD18 after balloon deflation.
      Modification of the expression of L-selectin was not noted. Production of
      superoxide anion by neutrophils was stimulated by plasma samples from the
      coronary sinus, but not by those from the femoral artery or vein. This plasma
      mediated neutrophil stimulation was prevented when the neutrophils were
      pretreated with platelet activating factor receptor antagonists BN52021 or
      BN50739. The platelet activating factor concentration detected in the coronary
      sinus was not higher than in control plasma. CONCLUSION: Brief ischaemia during
      coronary angioplasty leads to the release of soluble stimuli capable of inducing
      neutrophil integrin expression and free oxygen radical production. Platelet
      activating factor may act as an autocrine neutrophil stimulus under these
      conditions.

PMID- 8541169
TI  - Effect of low dose sotalol on the signal averaged P wave in patients with
      paroxysmal atrial fibrillation.
AB  - OBJECTIVE: To investigate the effects of low dose sotalol on the signal averaged
      surface P wave in patients with paroxysmal atrial fibrillation. DESIGN: A
      longitudinal within patient crossover study. SETTING: Cardiac departments of a
      regional cardiothoracic centre and a district general hospital. PATIENTS: Sixteen
      patients with documented paroxysmal atrial fibrillation. The median (range) age
      of the patients was 65.5 (36-70) years; 11 were men. MAIN OUTCOME MEASURES:
      Analysis of the signal averaged P wave recorded from patients not receiving
      antiarrhythmic medication and after 4-6 weeks' treatment with sotalol. P wave
      limits were defined automatically by a computer algorithm. Filtered P wave
      duration and energies contained in frequency bands from 20, 30, 40, 60, and 80 to
      150 Hz of the P wave spectrum expressed as absolute values (P20, P30, etc) and as
      ratios of high to low frequency energy (PR20, PR30, etc) were measured. RESULTS:
      No difference in P wave duration was observed between the groups studied (mean
      (SEM) 149 (4) without medication and 152 (3) ms with sotalol). Significant
      decreases in high frequency P wave energy (for example P60: 4.3 (0.4) v 3.3 (0.3)
      microV2.s, P = 0.003) and energy ratio (PR60: 5.6 (0.5) v 4.7 (0.6), P = 0.03)
      were observed during sotalol treatment. These changes were independent of heart
      rate. CONCLUSIONS: Treatment with low dose sotalol reduces high frequency P wave
      energy but does not change P wave duration. These results are consistent with the
      class III effect of the drug and suggest that signal averaging of the surface P
      wave may be a useful non-invasive measure of drug induced changes in atrial
      electrophysiology.

PMID- 8541170
TI  - Decreased platelet function in aortic valve stenosis: high shear platelet
      activation then inactivation.
AB  - OBJECTIVE: To elucidate the mechanism of the bleeding tendency observed in
      patients with aortic valve stenosis. DESIGN: A prospective study of high and low
      shear platelet function tests in vitro in normal controls compared with that in
      patients with severe aortic valve stenosis with a mean (SD) systolic gradient by
      Doppler of 75 (18) mm Hg before and at least 4 months after aortic valve
      replacement. SETTING: District general hospital. RESULTS: The patients showed
      reduced retention in the high shear platelet function tests. (a) Platelet
      retention in the filter test was 53.6 (12.6)% in patients with aortic valve
      stenosis and 84.8 (9.6)% in the controls (P < 0.001). (b) Retention in the glass
      bead column test was 49.8 (19.2) in the patients and 87.4 (8.7) in the controls
      (P < 0.001). (c) The standard bleeding time was longer in the patients (P <
      0.06). Results of the high shear tests (a, b, and c) after aortic valve
      replacement were within the normal range. The platelet count was low but within
      the normal range before surgery and increased postoperatively (P < 0.01). There
      were no differences in the results of standard clotting tests, plasma and
      intraplatelet von Willebrand's factor, or in 15 platelet aggregation tests using
      five agonists between patients with aortic valve stenosis and controls.
      CONCLUSIONS: The high shear haemodynamics of aortic valve stenosis modify
      platelet function in vivo predisposing to a bleeding tendency. This abnormality
      of platelet function is detectable only in vitro using high shear tests. The
      abnormal function is reversed by aortic valve replacement. High shear forces in
      vitro activate and then inactivate platelets. By the same mechanisms aortic valve
      stenosis seems to lead to high shear damage in vivo, resulting in a clinically
      important bleeding tendency in some patients.

PMID- 8541171
TI  - Pseudoaneurysm following aortic homograft: clinical implications?
AB  - OBJECTIVE: To determine the prevalence of pseudoaneurysm formation after aortic
      (left ventricular outflow tract) homograft implantation and to evaluate
      predisposing factors. METHODS: Echocardiographic data were analysed in 30
      patients for evidence of pseudoaneurysm formation after homograft implantation.
      Pseudoaneurysm was characterised as a perfused echo-free space between the
      homograft and the native aortic wall communicating with the left ventricular
      outflow tract. Clinical data were analysed for potential predisposing factors for
      pseudoaneurysm formation. RESULTS: Pseudoaneurysms were found in 22 of 30
      patients. Mean age, length of follow up after surgery, aortic systolic pressure
      gradient (15 (SD 12) v 10 (4) mm Hg), aortic root diameter, and size of the
      homografts were comparable in patients with and without pseudoaneurysm.
      preoperative infection, operating techniques, and whether first or reoperation
      did not affect pseudoaneurysm formation. However, pseudoaneurysms were often
      localised at the site of an abscess or a paravalvular leak after eradicated
      prosthetic valve endocarditis. CONCLUSIONS: (1) Doppler echocardiography
      demonstrates that pseudoaneurysm formation is common after aortic homograft
      implantation. (2) A prospective study is needed to clarify the prognostic
      importance of pseudoaneurysms. (3) The high incidence of pseudoaneurysm formation
      may lead to an improvement of surgical technique (application of fibrin glue).

PMID- 8541172
TI  - Disopyramide stress test: a sensitive and specific tool for predicting impending
      high degree atrioventricular block in patients with bifascicular block.
AB  - OBJECTIVE: To study the value of intravenous disopyramide as part of an invasive
      electrophysiological study in predicting impending high degree atrioventricular
      block in patients with bifascicular block. DESIGN: An invasive
      electrophysiological study was performed in the basal state and after the
      infusion of disopyramide (2 mg/kg body weight). The progression to high degree
      atrioventricular block was assessed by bradycardia-detecting pacemakers or
      repeated 12-lead electrocardiogram recordings, or both. PATIENTS: 73 patients
      with bifascicular block were included, of whom 25 had a history of unexplained
      syncope. The remaining 48 patients had no arrhythmia related symptoms and were
      included as controls. All patients had an ejection fraction of > 35%. RESULTS:
      After a mean follow up of 23 months, seven patients in the syncope group and
      three in the non-syncope group had a documented high degree atrioventricular
      block or pacemaker-detected bradycardia of < or = 30 beats/min for > or = 6 s.
      The sensitivity of the disopyramide test was 71% and the specificity 98%. The
      corresponding figures for an abnormal electrophysiological study in the basal
      state were 14% and 91%, respectively. CONCLUSIONS: The sensitivity of an invasive
      electrophysiological study in patients with bifascicular block and syncope can be
      markedly increased by the use of intravenous disopyramide. A positive test is a
      highly specific finding and warrants pacemaker implantation.

PMID- 8541173
TI  - Transient reduction of human left ventricular mass in carnitine depletion induced
      by antibiotics containing pivalic acid.
AB  - OBJECTIVE: To study the effect of induced carnitine depletion on myocardial
      structure and function. SUBJECTS AND DESIGN: 7 healthy adult volunteers given
      1200 mg pivmecillinam per day for 7-8 weeks were studied by echocardiography
      before and after 7-8 weeks of treatment and a 15 months follow up after the
      treatment period. SETTING: Teaching hospital. MAIN OUTCOME MEASURES: Carnitine
      concentration in serum, urine, and muscle and echocardiographic measurements.
      RESULTS: After 7-8 weeks of treatment the median free serum carnitine
      concentration was reduced to 7% and the median total muscle carnitine
      concentration to 46% of the pretreatment levels. The median diastolic
      interventricular septum thickness decreased by 14% (mean 26%, P = 0.028) and the
      median left ventricular mass by 10% (mean 20%, P = 0.018). Fifteen months later
      these dimensions had increased but not completely returned to pretreatment
      values. CONCLUSIONS: Extended treatment with pivalic acid containing antibiotics
      causes carnitine depletion which may lead to changes in cardiac structure.

PMID- 8541174
TI  - Appetite suppressants and primary pulmonary hypertension in the United Kingdom.
AB  - OBJECTIVE: Amphetamine-like appetite suppressants, particularly fenfluramines,
      have been implicated in the aetiology of primary pulmonary hypertension. At one
      specialist centre in France 20% of patients with primary pulmonary hypertension
      had been exposed to fenfluramine. The prevalence of primary pulmonary
      hypertension associated with fenfluramines and other appetite suppressants in the
      United Kingdom is unknown. This study was performed to measure prior exposure to
      appetite suppressants in patients with primary pulmonary hypertension. SETTING:
      Heart lung transplantation centres in England. PATIENTS: United Kingdom residents
      with proven primary pulmonary hypertension referred for consideration of heart
      lung transplantation. METHODS: Case surveillance study, obtaining data from the
      hospital and general practitioner's notes and directly from the patients or their
      relatives. RESULTS: 55 patients were identified. Drug histories were available
      from hospital records in all patients, from the general practitioner's notes in
      51, and from the patients or relatives in 44. Of these, 3 female patients had
      been exposed to appetite suppressants (2 fenfluramine, 1 diethylpropion): 2 have
      since died. In each case exposure was brief and apparently predated the
      development of symptoms by several years. CONCLUSIONS: Exposure of patients with
      severe primary pulmonary hypertension to fenfluramine and other appetite
      suppressants is uncommon in the United Kingdom unlike in France, where most of
      the cases associating primary pulmonary hypertension with fenfluramine use have
      originated. This may reflect more conservative prescribing of these agents in the
      United Kingdom.

PMID- 8541175
TI  - Left atrial size and function: assessment using echocardiographic automatic
      boundary detection.
AB  - OBJECTIVE: To evaluate the waveforms of left atrial area changes obtained by
      automated boundary detection with newly developed acoustic quantification
      technology. DESIGN: All subjects had measurements of left atrial areas taken in
      the apical four chamber, parasternal long axis, and parasternal short axis views
      using both conventional echocardiographic methods and automatic boundary
      detection on two occasions separated by at least a week. On the second visit
      measurements were also repeated in healthy volunteers after acute intravenous
      volume loading with 1 litre of saline over 2-5 minutes. SETTING: A university
      medical school echocardiographic laboratory. SUBJECTS: 12 healthy male volunteers
      and 8 patients with cardiac disease (5 with congestive heart failure, 1 with
      mitral stenosis, and 2 with hypertensive left ventricular hypertrophy, and
      dilated left atria). RESULTS: There was close correlation between conventionally
      derived left atrial areas and those obtained by automatic boundary detection,
      particularly in the apical four chamber view (r = 0.98). Both inter and intra
      observer variabilities (coefficient of variation) for left atrial areas measured
      by automatic boundary detection were good (4.7-14.2% and 8.1-18.6% respectively).
      The reproducibility (coefficient of variation) for derived indices of left atrial
      function, however, was much poorer (10.4-104.8% and 12.5-88% respectively). After
      acute volume loading significant increases in left atrial area were observed at
      all stages in the cardiac cycle. CONCLUSIONS: These data demonstrate that
      although the reproducibility of left atrial functional indices is poor,
      instantaneous left atrial cavity measurements with automatic boundary detection
      are reproducible. This suggests that automatic boundary detection may assist in
      serial non-invasive measurement of left atrial size to assess disease states and
      treatments.

PMID- 8541176
TI  - Long term results of fast pathway ablation in atrioventricular nodal reentry
      tachycardia using a modified technique.
AB  - OBJECTIVE: To assess immediate and long term success of "fast" pathway catheter
      ablation with graded use of radiofrequency energy in patients with classic
      atrioventricular nodal reentrant tachycardia (AVNRT) and evaluate clinical,
      procedure related, and electrophysiological features affecting long term results.
      DESIGN: 31 consecutive patients with classic AVNRT at electrophysiological study,
      who were candidates for radiofrequency ablation. Patients were followed for an
      average of 24 months after ablation. SETTING: All studies and ablations were
      performed in an electrophysiological laboratory under fluoroscopic guidance using
      standard electrophysiological techniques. INTERVENTION: Radiofrequency
      application was performed at the site of proximal His bundle electrogram with A:V
      ratio of > 1. It was started at 10 W with increment of 5 W to a maximum of 25 W
      at 60 s. With the onset of junctional rhythm, atrial pacing was begun in order to
      monitor the PR interval. Application was terminated prematurely with a non
      conducted P wave, continued prolongation of the PR interval beyond 50% of the
      baseline, or a threefold rise in impedance. RESULTS: Successful ablation was
      possible in 30/31 patients (97%) with an average of seven applications (range 1
      10). It was associated with significant prolongation of PR interval (P < 0.001)
      and AV Wenckebach cycle length (P = 0.01). Ventriculo-atrial conduction was
      abolished in 24/30 patients (82%) with successful ablation. Two patients
      developed transient complete heart block (3 and 12 min) and one persistent right
      branch block. Four patients had late recurrence. Presence of ventriculo-atrial
      block was the only electrophysiological index predictive of long term success (P
      = 0.01). CONCLUSIONS: Graded use of radiofrequency energy and atrial pacing to
      monitor PR interval decreases the risk of atrioventricular block in patients
      undergoing fast pathway ablation for AVNRT. Ventriculo-atrial block is predictive
      of long term success and should be a preferred end point for fast pathway
      ablation.

PMID- 8541177
TI  - Use of lead adjustment formulas for QT dispersion after myocardial infarction.
AB  - OBJECTIVE: To determine whether lead adjustment formulas for correcting QT
      dispersion measurements are appropriate in patients after myocardial infarction.
      DESIGN: Retrospective analysis of QTc dispersion measurements in 461
      electrocardiograms (ECGs). Data are presented as uncorrected QTc dispersion
      "adjusted" for a number of measurable leads and coefficient of variation of QTc
      intervals for ECGs in which between six and 12 leads had a QT interval that could
      be measured accurately. PATIENTS: Patients were drawn from the placebo arm of the
      second Leicester Intravenous Magnesium Intervention Trial. Some 163 patients who
      subsequently died and an equal number of known survivors had ECGs recorded on day
      2 or 3 of acute myocardial infarction. ECGs were also available in 135 of these
      patients from at least 1 month postinfarct. RESULTS: The most common lead in
      which a QT interval measurement was omitted was aVR (n = 176), the least common
      lead was V3 (n = 13). The longest QTc interval measured was most usually in lead
      V4 (n = 72) and the shortest in lead V1 (n = 67). As the number of measurable
      leads decreased there was a small, nonsignificant increase in QTc dispersion from
      12 lead to eight lead ECGs (mean (SD) 100 (35.5) v 109.5 (47.9) ms). Lead
      adjusted QTc dispersion (QTc dispersion/square root of the number of measurable
      leads) showed a large, significant increase when the number of measurable leads
      decreased from 12 to eight (28.9 (10.3) v 38.7 (16.1) ms, P < 0.001). A similar
      trend was seen for coefficient of variation of QTc intervals (standard deviation
      of QTc intervals/mean QTc interval 64.3 (2.19) v 8.45 (3.94)%, P < 0.001).
      CONCLUSIONS: Lead adjustment formulas for QT dispersion are not appropriate in
      patients with myocardial infarction. Large differences in lead adjusted QTc
      dispersion are produced, dependent on the number of measurable leads, for very
      small differences in QTc dispersion. It is recommended that QT dispersion is
      presented as unadjusted QT and QTc dispersion, stating the mean (SD) of the
      number of leads in which a QT interval was measured.

PMID- 8541178
TI  - Effect of the increasing use of coronary angioplasty on outcome at one year in
      patients with unstable angina.
AB  - OBJECTIVE: To determine whether the increasing use of percutaneous transluminal
      angioplasty in patients with unstable angina has reduced the need for bypass
      surgery and whether this change in the choice of treatment affected the outcome
      at one year in patients with unstable angina who were admitted to hospital in two
      different periods of time. DESIGN: Retrospective analysis of consecutive patients
      with unstable angina (angina at rest with ST-T changes during pain) who underwent
      coronary arteriography in two different periods of time. PATIENTS: 158 patients
      were admitted to hospital between January 1988 and June 1989 (group 1) and 140
      patients admitted between January 1992 and June 1993 (group 2). RESULTS: Coronary
      angioplasty procedures nearly doubled from 29% in group 1 to 56% in group 2
      whereas bypass surgery decreased from 36% in group 1 to 23% in group 2 (P <
      0.01). Coronary angioplasty increased and bypass surgery decreased in patients
      with one vessel disease (P < 0.01), two vessel disease (P < 0.05), and three
      vessel disease (P < 0.01). Coronary angioplasty also increased and bypass surgery
      decreased in refractory angina and in patients with ejection fraction < 0.50
      (both P < 0.05). At 1-year follow up, 14 patients in group 1 (9%) and 10 in group
      2 (7%) either died or had myocardial infarction (P = NS). Revascularisation
      procedures were needed in 16 group 1 patients (10%) and 27 group 2 patients (19%,
      P < 0.05). CONCLUSIONS: Coronary angioplasty became more widely used in patients
      with unstable angina. This reduced the need for bypass surgery in patients with
      multivessel disease, refractory angina, and depressed left ventricular function.
      This change in treatment did not affect 1-year mortality or the myocardial
      infarction rate. More patients in the more recent group in which angioplasty was
      the preferred treatment required a further revascularisation procedure than in
      the earlier group in which bypass grafting was more often used as the initial
      treatment.

PMID- 8541179
TI  - Hepatitis B immunisation among invasive cardiologists: poor compliance with
      United Kingdom guidelines.
AB  - OBJECTIVES: To assess the compliance of invasive cardiologists in the United
      Kingdom with recently accepted national guidelines on the protection of health
      care workers and patients from hepatitis B. To determine levels of awareness of
      the infectivity and prevalence of the virus and current attitudes towards
      screening of patients before cardiac catheterisation and surgery. DESIGN:
      Anonymous postal survey by questionnaire from the University Hospital of Wales,
      Cardiff. The questionnaire established the respondent's position, knowledge of
      hepatitis B, current immunological state, and policy towards the routine
      screening of patients for hepatitis B carriage. PARTICIPANTS: All British
      cardiologists of consultant or senior registrar grade involved in invasive
      procedures. RESULTS: The response rate was 78% (211/271). 20% of respondents had
      never been vaccinated against hepatitis B and about a third of those vaccinated
      had not complied correctly with the recommended immunisation regimen. There was
      little uniformity in practices for screening patients for hepatitis B carriage
      before invasive procedures, and the level of knowledge concerning the prevalence
      of hepatitis B and the risks of inoculation was poor. CONCLUSIONS: Invasive
      cardiologists are at high risk of inoculation with hepatitis B. Nationally agreed
      guidelines are designed to protect both medical staff and patients against the
      risk of infection but currently they are ill heeded.

PMID- 8541180
TI  - Endovascular stents in children under 1 year of age: acute impact and late
      results.
AB  - OBJECTIVES: To review efficacy and safety of endovascular stent implants in
      children < 1 year of age with congenital heart lesions. DESIGN: Retrospective
      study of patients in a tertiary care setting. PATIENTS: 26 children (median age
      of 4.7 months, range 2 days to 1 year) with various vascular obstructive lesions.
      INTERVENTION: Percutaneous or intraoperative implantation of balloon expandable
      endovascular stents. RESULTS: Optimal stent placement was obtained in 31 of the
      37 deployed implants. Complications resulted primarily from stent malpositioning
      and one episode of bleeding at a puncture site. Stent implantation in three
      patients with a restrictive arterial duct allowed for patency and five patients
      with conduit stenosis had mean (SD) right ventricule to systemic artery pressure
      ratios falling from 0.99 (0.20) to 0.52 (0.18) (P < 0.05). In 10 patients with
      pulmonary artery stenosis, the mean vessel diameter increased from 2.8 (0.9) mm
      to 5.8 (1.4) mm (P << 0.001). No clinical improvement was seen in two patients
      because of diffuse hypoplasia of the pulmonary vessels. Nine of 10 patients with
      miscellaneous obstructive lesions improved clinically. Recatheterisation was
      performed in 19 patients (median 8 months, range 12 days to 28 months) and 11
      patients required redilatation (17 stents). CONCLUSIONS: Stent implantation is
      technically feasible in infants and under specific circumstances may provide an
      alternative to surgical palliation or avoid reoperation. The long term impact on
      clinical course, however, involves further interventions directed at stent
      management.

PMID- 8541181
TI  - Extreme pulsus alternans presenting as 2:1 electromechanical dissociation.

PMID- 8541182
TI  - Dr Black's favourite disease.

PMID- 8541183
TI  - Radiofrequency current caused slowing of non-reentrant idiopathic right
      ventricular tachycardia originating from a wide arrhythmogenic area.
AB  - Radiofrequency catheter ablation was attempted in a patient with non-reentrant
      idiopathic right ventricular tachycardia (VT). Endocardial mapping indicated that
      the VT originated in the outflow tract of the right ventricle; however, an
      electrogram with an almost the identical activation time was recorded from an
      area extending to 1.0 x 2.0 cm. Each application of radiofrequency current within
      the area terminated VT, but a progressively slower VT with the same QRS
      configuration was induced until the area was covered by separate radiofrequency
      lesions. A progressive prolongation of VT cycle length might be related to a
      residual arrhythmogenic myocardium. Termination and slowing of the VT rate can be
      a hallmark of efficacy of each radiofrequency lesion.

PMID- 8541184
TI  - Severe coronary vasospasm associated with hyperthyroidism causing myocardial
      infarction.
AB  - A 48 year old woman presented with angina after an anterior myocardial infarction
      and was found to be hyperthyroid. Coronary angiography showed a stenosis of the
      left coronary os and a long, severe stenosis of the left anterior descending
      artery which was partially relieved by glyceryl trinitrate. Three months later,
      after radioactive iodine treatment had rendered her euthyroid, repeat coronary
      angiography showed entirely normal coronary arteries. This unusual case
      establishes an association between hyperthyroidism and coronary vasospasm
      resulting in myocardial infarction.

PMID- 8541185
TI  - Heart rate variability in left ventricular hypertrophy.

PMID- 8541186
TI  - Risks and results of surgery.

PMID- 8541187
TI  - Percutaneous balloon dilatation of the mitral valve in critically ill young
      patients with intractable heart failure.

PMID- 8541188
TI  - Strut fracture of the convexo-concave Bjork-Shiley mitral valve prosthesis.

PMID- 8541189
TI  - Cost-effective carotid endarterectomy in community practice.
AB  - The purpose of this study was to compare hospital charges for carotid
      endarterectomy on a surgeon-specific basis. The cost of carotid endarterectomy is
      influenced by preoperative evaluation, operating time, use of the intensive care
      unit, length of hospital stay, and surgical results. Length of stay and average
      hospital charges for 18 doctors performing 344 carotid endarterectomies at three
      hospitals were analyzed. Outcome data were also reviewed. The results
      demonstrated a wide variation in hospital charges among surgeons. Surgeons using
      the most cost-effective measures achieved comparable or superior outcomes. In an
      era of managed care, severe cost constraints mandate that surgeons perform
      similar studies in their own communities so that cost-effective clinical pathways
      can be developed. With the use of appropriate guidelines, carotid endarterectomy
      can be performed at relatively low cost without sacrificing quality.

PMID- 8541190
TI  - Concurrent abdominal aortic aneurysm and urologic neoplasm: an argument for
      simultaneous intervention.
AB  - This report describes the surgical management of 24 patients with concurrent
      abdominal aortic aneurysm (AAA) and urinary tract neoplasm. The patient
      population consisted of 22 men and two women whose average age was 65.5 years.
      AAA sizes ranged from 3.1 to 9.0 cm (mean 5.2 cm) in diameter. Urinary tract
      neoplasms included transitional cell carcinoma (TCC) of the bladder (n = 19),
      adenocarcinoma of the prostate (n = 3), and TCC of the renal pelvis (n = 2).
      Urologic procedures included radical prostatectomy, radical nephroureterectomy,
      and radical cystoprostatectomy with continent or ileal loop urinary diversion.
      The AAA was resected at the time of the urologic procedure in 12 patients (group
      I) or prior to the urologic procedure in five patients (group II) and was left in
      situ in seven patients (group III: AAA diameter 3.1 to 5.5 cm). All patients but
      one in group I recovered without complications. One patient developed an
      infection postoperatively as a result of fluid collection anterior to the aortic
      vascular graft; the fluid was successfully drained and the patient subsequently
      recovered uneventfully. All patients in group II had a marked retroperitoneal
      desmoplastic reaction at the time of the urologic procedure as a result of prior
      aneurysmectomy, which complicated the ureteral dissection. One patient later
      required an ileal ureteral reconstruction for obliterative fibrosis of the
      ureter. At a mean follow-up of 34 months, no infectious or mechanical
      complications of the vascular prosthesis occurred in group I or II. Eight
      patients in group I and two in group II are alive. Three have died of metastatic
      disease and two of myocardial infarction. Of the seven patients in group III,
      four subsequently required AAA resection for an increase in AAA size and three
      have died.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541191
TI  - Comparison of the utility of CT scans and intravascular ultrasound in
      endovascular aortic grafting.
AB  - Using CT scans and intravascular ultrasound (IVUS), aortic, aneurysm neck, and
      endoluminal graft cross-sectional dimensions were compared in a canine model
      before and after placement of endoluminal grafts in normal aortas (n = 10) and in
      artificially constructed abdominal aortic aneurysms (n = 15). Measurement of
      diameters (n = 83) revealed an average difference or bias between imaging
      modalities of 0.17 +/- 0.92 mm. Measurements obtained using IVUS were slightly
      larger than CT values (8.84 +/- 1.0 vs. 8.65 +/- 1.1, p < 0.03) but correlated
      very well by linear regression analysis (r = 0.948, p < 0.02). Analysis of cross
      sectional area (n = 44) revealed an average difference or bias of 7.21 +/- 7.76
      mm2 between the two modalities. Again IVUS measurements were larger than CT
      measurements (65.0 +/- 16.5 vs. 57.9 +/- 11.9, p < 0.001) and linear regression
      analysis showed less correlation (r = 0.897, p < 0.001). Qualitative assessment
      of the graft and stent characteristics was more precise using IVUS. Graft
      folding, stent-aorta interfaces, and thrombus formation were easily identified by
      IVUS, whereas these more subtle characteristics were missed by CT scanning and
      arteriography. These studies demonstrate that IVUS measurements were slightly
      larger than CT values; however, both modalities demonstrate small bias and good
      correlation. Qualitative analysis of the aneurysmal aorta and endoluminal graft
      using IVUS is comparable to and in some respects more detailed than measurements
      from CT scanning and arteriography.

PMID- 8541192
TI  - Clinical and CT evaluation of a new stretch polytetrafluoroethylene aortic graft.
AB  - A new stretch polytetrafluoroethylene (PTFE) aortic graft became available for
      clinical use in early 1991. We prospectively evaluated our first 107 stretch
      aortic PTFE grafts by means of serial CT imaging and compared them with a cohort
      of concurrently placed Dacron grafts. Stretch PTFE requires no preclotting and is
      claimed to resist long-term dilation and conform well to anastomoses. Consecutive
      patients undergoing placement of stretch PTFE grafts were seen at least yearly.
      Within the first 2 years after implantation, contrast-enhanced CT scans of the
      abdomen and pelvis were obtained. Caliper measurements were made of the native
      arteries and the body and any limbs of the aortic grafts. Graft elongation was
      assessed by noting distortions from the normally circular or minimally ovoid
      configuration of the grafts on transverse CT images. Indications for grafting
      were elective repair of abdominal aortic aneurysm in 60 patients, aortoiliac
      occlusive disease in 31, both aneurysm and occlusive disease in eight, and
      ruptured abdominal aortic aneurysm in eight. The overall operative mortality rate
      was 6.5%. There were two early postoperative graft limb thromboses resulting from
      hypercoagulable states, and there was one graft infection. Mean follow-up was
      14.1 months (range 1 to 34 months). CT scans were obtained from 61 patients with
      stretch PTFE grafts and 10 with concomitantly placed Dacron grafts. Ten patients
      had two or more postoperative CT scans. Primary stretch PTFE patency was 98% and
      secondary patency, 100%. There was significantly less dilation of both the graft
      body and limbs in the stretch PTFE group (body mean 16.5%, range 6.3% to 28.1%;
      limb mean 19.3%, range 10% to 43%) compared to the Dacron group (body mean 33%,
      range 22% to 78%; limb mean 62%, range 12.5% to 88.9%) (p < 0.01, unpaired t
      test).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541193
TI  - Carbon dioxide/digital subtraction arteriography-assisted transluminal
      angioplasty.
AB  - During a 62-month period, carbon dioxide was used to supplement or completely
      replace iodinated contrast agents in performing 27 transluminal angioplasties in
      26 patients. The arterial segments addressed included the following: renal in two
      cases, iliac in five, femoral/popliteal in 15, infrapopliteal in two, and
      combined in three. Indications for intervention included lower extremity gangrene
      in 11 cases, ischemic ulceration in 10, rest pain in three, claudication in one,
      and ischemic nephropathy in two. Contraindications to iodinated contrast agents
      included renal insufficiency resulting from diabetes (n = 20) or ischemic
      nephropathy (n = 2) and congestive heart failure (n = 4). Eight procedures used
      carbon dioxide as the sole contrast agent, whereas 19 required supplementation of
      carbon dioxide with a mean of 39 ml of nonionic contrast medium. Technical
      success was achieved in 25 procedures with significant hemodynamic improvement in
      20 patients. Complications included transient deterioration in renal function in
      two patients and myocardial infarctions in two. At 30 days 18 patients had
      demonstrated significant clinical improvement. Patients at high risk for
      iodinated contrast-related complications may undergo transluminal angioplasty
      using carbon dioxide/digital subtraction arteriography to reduce or eliminate the
      need for iodinated contrast agents.

PMID- 8541194
TI  - Stenting without thrombolysis for aortoiliac occlusive disease: experience in 14
      high-risk patients.
AB  - Stenting without thrombolysis of 16 occluded iliac artery segments and one
      occluded infrarenal abdominal aorta was attempted in 14 patients. All patients
      were either considered to be prohibitive operative risks or had contraindications
      to thrombolytic therapy. Indications for limb reperfusion included rest pain,
      disabling claudication, or dry gangrene. Successful recanalization was achieved
      primarily in 13 patients with self-expandable Wallstents, balloon-expandable
      Palmaz stents, or a combination of the two stents. Follow-up was carried out in
      all patients in whom recanalization was successful. All stented patients showed
      symptomatic improvement, and the mean preprocedure ankle/brachial index, which
      was 0.31, improved to 0.78 after the procedure (p = 0). Complications included a
      vertebrobasilar stroke during the procedure in one patient, perforation during
      angioplasty of a stenotic but nonoccluded external iliac artery in one, and
      dissection of the distal external iliac artery in one. Distal embolization did
      not occur. Percutaneous recanalization of aortoiliac occlusions without initial
      thrombolysis is possible and has a high potential for technical success.
      Additional data and longer follow-up are still needed, but this procedure may
      provide a reasonable, less invasive option in some patients at high surgical risk
      or in patients who have contraindications to thrombolytic therapy.

PMID- 8541195
TI  - Infected lower extremity extra-anatomic bypass grafts: management of a serious
      complication in high-risk patients.
AB  - To determine optimal management and outcome of infected extra-anatomic bypass
      grafts (EABG), we reviewed 28 patients (19 men and 9 women; mean age 70 years)
      treated over a 13-year period. Mean follow-up was 42 months. There were 16
      axillofemoral (AF), 10 femorofemoral (FF), and two axillopopliteal (AP) grafts.
      Risk factors included previous prosthetic graft infection in 13 patients,
      enterocutaneous fistula in two, and mycotic aortic aneurysm in one. Initial
      management involved complete graft excision in 12 patients, partial graft
      excision in 10, and nonresectional therapy in six. Failure of nonresectional
      therapy and partial excision in three patients each required further operative
      intervention with graft excision. Reconstruction in patients eventually requiring
      graft excision (n = 25) entailed placement of a new prosthetic AF or AP graft in
      eight, an autogenous FF graft in five, combined prosthetic AF and autogenous FF
      bypass in two, autogenous iliofemoral bypass in one, obturator bypass in one, or
      no reconstruction in eight. Four autogenous FF reconstructions thrombosed
      immediately postoperatively, and three prosthetic reconstructions became
      infected. The mortality rate was 18% (FF = 20%, AF = 19%, AP = 0%). The
      amputation rate was 25% (AP = 100%, AF = 25%, FF = 10%) and was higher without
      arterial reconstruction (56% vs. 12%, p = 0.02). Two patients required
      hemipelvectomies and one had bilateral hip disarticulation. We conclude that EABG
      infections can be successfully treated but carry significant morbidity and
      mortality. Optimal management includes EABG resection and prompt
      revascularization, bearing in mind the risk of early thrombosis in autogenous
      grafts and reinfection in prosthetic grafts.

PMID- 8541196
TI  - An unusual variant of popliteal artery entrapment.
AB  - A 43-year-old woman presented with incapacitating exertional pain in the right
      foot, ankle, and lower calf of 1 years' duration following a minor ankle sprain.
      Evaluation by several physicians had been inconclusive. Physical examination
      identified normal pedal pulses at rest but obliteration of pulses with active
      plantar flexion. Segmental pressures were normal at rest and duplex scanning
      showed occlusion of the popliteal artery with active plantar flexion. The
      findings were confirmed by arteriography despite a normal course of the popliteal
      artery. Magnetic resonance imaging (MRI) showed no muscular abnormality. At
      exploration entrapment was noted to be the result of compression by branches of
      the sural nerve and vein as they coursed medially inserting into the medial head
      of the gastrocnemius muscle. Division of the neurovascular bundle resulted in
      complete resolution of symptoms and arterial compression on duplex examination
      postoperatively. This case was unusual because of the patient's age, sex, and the
      pathologic findings that had not been previously reported. In this case MRI was
      not useful in demonstrating a muscular or neurovascular bundle abnormality,
      supporting the use of duplex scanning as the noninvasive diagnostic modality of
      choice.

PMID- 8541197
TI  - Percutaneous transluminal angioplasty in adults less than 45 years of age with
      premature lower extremity atherosclerosis.
AB  - Despite poor results reported with conventional vascular bypasses in young adults
      with ischemia from premature lower extremity atherosclerosis (PLEA), little
      attention has been given to alternative revascularization techniques. This study
      evaluated 32 patients (21 males and 11 females) < 45 years of age with PLEA who
      underwent 53 primary percutaneous transluminal angioplasty (PTA) procedures for
      treatment of 46 ischemic limbs. A residual arterial stenosis < 30% was achieved
      in 83% of PTA sites. Mean degree of stenosis decreased from 79.9% to 24.1% (p <
      0.0001). Clinical improvement in ischemic symptoms was obtained in 39 (85%)
      limbs. Hemodynamic improvement was achieved in 31 (70%) of 40 limbs as documented
      by ankle/brachial indices. All criteria for early clinical success were met in
      70%. Another 13% met all criteria except that the residual stenosis was < 50%.
      Hematoma and early restenosis were reported in two patients each. Mean follow-up
      was 27.3 months (range 1 to 84 months). Cumulative patency by life-table analysis
      was 81% at 1 year, 77% at 2 years, and 71% at 3 years. Thirteen (41%) patients
      required secondary PTA or bypass; 85% were performed within 1 year. Two patients
      had adjunctive bypasses; six (19%) were performed after PTA failure. Only one
      (3%) patient required major amputation. Neither cardiovascular risk factors,
      treatment indication, location of the diseased arterial segment, nor quality of
      distal runoff vessels predicted the need for secondary PTA or surgical
      procedures. PTA of the proximal arteries in young patients with PLEA is an
      effective primary revascularization technique with results comparable to those of
      conventional operative revascularization procedures.

PMID- 8541198
TI  - Skin closure and the incidence of groin wound infection: a prospective study.
AB  - Groin wound infection is a dreaded complication of vascular surgery and may
      jeopardize an underlying graft. A variety of skin closures have been used and the
      object of this study was to prospectively determine the relationship between skin
      closure and wound infection. One hundred fourteen consecutive patients (70 men
      and 44 women) undergoing bypass surgery with a groin incision (n = 173) were
      randomly assigned to skin closure with subcuticular Maxon, interrupted nylon,
      continuous nylon, or clips following a standard two-layer closure of subcutaneous
      tissue. Fourteen (12%) patients had diabetes and 50 (44%) had digital ulceration
      and gangrene. Aortofemoral bypass was performed in 25% of the patients and
      infrainguinal bypass in the remaining 75%. Perioperative wound cultures were
      obtained before closure. Wounds were inspected and cultures repeated on
      postoperative days 3, 5, 7, 10, and 14. Infection was defined as a positive
      culture. Groin wound infection occurred in 3% of the population and graft
      infection in 0.6%. The type of suture did not influence the incidence of
      infection. This study failed to demonstrate a significant difference in the
      incidence of wound infection with the use of different suture materials. We
      conclude that suture material should be selected on the basis of surgeon
      preference and costs.

PMID- 8541199
TI  - Use of inferior vena cava filters in the Medicare population.
AB  - To examine the use of inferior vena cava (IVC) filters, we performed a population
      based study using a 5% random sample of the United States Medicare population
      (1.25 million persons). Filter placement and its timing relative to diagnosis of
      venous thromboembolism (VTE) were determined using both hospital and physician
      Medicare billing codes after detailed review of large samples of complete
      individual claims records. Comorbid conditions and mortality were also noted.
      From July 1986 through June 1989, a total of 806 patients in the sample
      population received IVC filters. Mortality rates after filter placement were
      high: 16% during initial hospitalization, 32% within 6 months of filter
      placement, and 48% after 2 years. However, only 3 (1%) of 423 patients who
      underwent filter placement without the diagnosis of pulmonary embolism (PE)
      suffered PE within 1 year of filter placement. Use of IVC filters increased
      significantly over the study period (p < 0.001). Rates of filter placement among
      the nine census divisions of the United States differed significantly (p <
      0.001). An East-West trend was notable with the highest rate (37 filters/100,000
      enrollees/yr) in New England, as compared with 14 filters/100,000 enrollees/yr in
      the Pacific Division. No explanation for these regional differences was evident
      after patient demographics and comorbidity were examined. Vena cava filters
      prevent PE for at least 1 year after placement. The frequency of IVC filter use
      in elderly patients is increasing and varies substantially by region. Although
      reasons for these trends are unclear, these findings suggest the need for uniform
      practice guidelines for IVC filter placement.

PMID- 8541200
TI  - Evaluation of dopexamine hydrochloride as a renoprotective agent during aortic
      surgery.
AB  - Thirty-two patients undergoing elective infrarenal aortic surgery were randomly
      assigned to receive a perioperative infusion of either dopexamine hydrochloride
      at a rate of 2 micrograms/kg/min (n = 15) or 0.9% saline solution as placebo (n =
      17). Renal function was monitored by regular measurements of serum creatinine
      levels. There were significant mean percentage increases in serum creatinine (p <
      0.001) at all time points up to 3 days postoperatively in the placebo group but
      only at 2 and 12 hours in the dopexamine group. It was concluded that dopexamine
      hydrochloride confers renal protection in patients undergoing aortic
      reconstruction.

PMID- 8541201
TI  - Multiple nonanastomotic aneurysms in an external velour ringed Dacron
      femoropopliteal vascular prosthesis.
AB  - Nonanastomotic aneurysms of arterial prosthetic grafts are an infrequent but well
      documented complication of arterial bypass surgery. Several cases of
      nonanastomotic aneurysm formation of the external velour-type Dacron graft have
      been reported. We present a case of an external velour ringed Dacron (Sauvage
      EXS) femoropopliteal bypass graft with multiple nonanastomotic aneurysms. An
      extensive review of the English literature shows this to be the first reported
      case of multiple aneurysms occurring in this type of prosthesis.

PMID- 8541202
TI  - Ruptured infected popliteal artery aneurysm.
AB  - We describe an unusual presentation of an infected popliteal aneurysm. To our
      knowledge rupture of an aneurysm associated with Salmonella at this site has not
      previously been reported. The management of infected aneurysms is discussed.

PMID- 8541203
TI  - Nondysplastic saccular aneurysm of the internal carotid artery.
AB  - An unusual case of nondysplastic saccular aneurysm associated with elongation of
      the extracranial internal carotid artery is reported. The artery was normal
      except for a punch-hole defect in the media, which distinguished it from true
      fibromuscular dysplasia. Although neurologic symptoms and treatment were not
      specific, this case is interesting in that the exact cause of the aneurysm
      remains unknown.

PMID- 8541204
TI  - Nondissecting thoracoabdominal aortic aneurysms: Part I.

PMID- 8541205
TI  - Wnt4 affects morphogenesis when misexpressed in the zebrafish embryo.
AB  - The Wnts are a family of secreted glycoproteins involved in cell-cell signalling
      and pattern formation during development, although the extent to which various
      Wnts are functionally equivalent remains unclear. We have cloned zebrafish (Danio
      rerio) wnt4, characterized its expression, and compared its activity relative to
      other Wnts. The wnt4 transcript is first detected early in somitogenesis, in the
      dorsocaudal region of the forebrain, and then appears in the dorsal and lateral
      regions of the caudal hindbrain and neural keel. During somitogenesis, wnt4
      appears in the floor plate, and this expression is absent in cyclops mutants,
      which lack floor plate. wnt4 is also expressed in the developing pronephros and
      gill slit. To characterize the biological activity of wnt4, synthetic zebrafish
      wnt4 mRNA was injected into embryos of zebrafish and Xenopus laevis. The
      phenotypic effects of misexpression in the zebrafish include cyclopia, misfolding
      in the brain, and an anteriorly forking notochord. Comparison of the phenotypes
      arising from misexpression of wnt4 and Xwnt-5A in both organisms suggests close
      parallels in the response to these Wnts. Our data suggest that wnt4, like Xwnt
      5A, inhibits cell movements, and that these Wnts define a functional class
      distinct from the class which includes Wnt-1, Xwnt-3A and Xwnt-8.

PMID- 8541206
TI  - Developmental effects of over-expression of normal and mutated forms of a Xenopus
      NF-kappa B homologue.
AB  - High level over-expression of XrelA1, a homologue of the p65 sub-unit of NF-kappa
      B and of Drosophila dorsal, arrests Xenopus development at the gastrula stage,
      producing a reduction in the levels of expression of various genes of
      developmental interest without general reduction in transcription or cessation of
      cell division. There is little Goosecoid expression, even though a dorsal lip
      forms. At lower levels XrelA1 mRNA primarily produces disruption of the mid
      dorsal axis. A dominant interference gene product, delta 222, produces mainly
      posterior, but also anterior abnormalities. On the basis of these results we
      postulate that the role of XrelA1 in the vertebrate embryo is unlikely to be in
      dorsoventral development, but more likely in the formation of the termini.

PMID- 8541207
TI  - Changes in gene expression during post-eclosional development in the olfactory
      system of Drosophila melanogaster.
AB  - We have found that the expression of some genes in Drosophila melanogaster
      changes during the life of the adult fly. These changes can be illustrated by the
      use of enhancer trap lines which mark the expression of particular genes in the
      adult fly. Although the fly is considered able to perform most necessary adult
      functions within the first 72 h after eclosion from the pupal case, we find
      changes in expression over the first 10 days of life in the antennae of several
      of the genes we have examined. Some genes change by increasing from an initially
      low level of expression of the marked gene, while other lines, which we have
      termed 'late-onset' genes, show no expression of the marked gene until 4-5 days
      following eclosion. In contrast, some genes decrease their expression during the
      first 10 days of life. The changes in gene expression seen over the first 10 days
      of the fly's adult life provides molecular evidence of the many maturational
      changes occurring during the early life of the adult fly.

PMID- 8541208
TI  - The murine LIM-kinase gene (limk) encodes a novel serine threonine kinase
      expressed predominantly in trophoblast giant cells and the developing nervous
      system.
AB  - Throughout vertebrate embryogenesis, membrane bound and intracellular protein
      kinases govern the fundamental decisions necessary for coordinated cell growth
      and differentiation. Here we have characterized limk, a novel protein kinase with
      serine threonine substrate specificity which also contains two LIM domains. We
      used Northern blot and in situ hybridization techniques to determine its pattern
      of expression in early mouse development. Between 7.5 and 8.5 d.p.c., limk is
      expressed in three broad domains within the embryo, the neuroectodermal of the
      prospective forebrain and mid-brain regions, the cardiac mesoderm, and the newly
      formed definitive endodermal derivatives the foregut and hindgut. By 10.0 d.p.c.
      limk remains prominently expressed in the ventromedial regions of the developing
      forebrain and midbrain, with continued expression in the hindgut. In adults limk
      is expressed most prominently in the brain. Additionally we have shown that limk
      is most abundantly expressed in the trophoblast giant cells, from 4.5 d.p.c.
      onwards. Moreover, high levels of limk expression is associated with the overt
      formation of giant cells from diploid progenitors, suggesting an involvement for
      limk in the differentiation of this highly specialized extra-embryonic cell type.

PMID- 8541209
TI  - Switch in the expression of the K19/K18 keratin genes as a very early evidence of
      testicular differentiation in the rat.
AB  - It has been shown previously that acidic K18 and K19 keratins display a
      differential immunohistochemical pattern of expression during sexual
      differentiation of the gonads in the rat (Fridmacher et al. (1992) Development
      115, 503-517). The present results indicate that K18 and K19 gene expression is
      regulated at the transcriptional level. The analysis was performed by Northern
      Blot, reverse transcriptase polymerase chain reaction (RT-PCR) and in situ
      hybridization. PCR products were cloned, sequenced and used as species-specific
      K18 and K19 riboprobes for in situ hybridization. K19 mRNA but not K18 mRNA was
      detected in undifferentiated gonads and in somatic cells of ovarian cords
      throughout the fetal ovary development. K18 mRNA expression appeared in male
      gonads, at 13.5 days of gestation, at the onset of testicular differentiation, as
      the first Sertoli cells differentiated and aggregated to form seminiferous cords.
      As testicular differentiation progressed, K19 mRNA disappeared and, from 14.5
      days of gestation on, fetal Sertoli cells expressed exclusively K18 mRNA. The
      changes in the transcriptional activity of K19 and K18 genes, observed in male
      gonads, occur characteristically at the very beginning of testicular
      differentiation. In the male pathway of sexual differentiation, the switch in
      K19/K18 gene expression is, in addition to the activation of the anti-Mullerian
      hormone gene, the most precocious regulative event occurring after the expression
      of the testis determining factor SRY.

PMID- 8541210
TI  - The Drosophila trithorax proteins contain a novel variant of the nuclear receptor
      type DNA binding domain and an ancient conserved motif found in other chromosomal
      proteins.
AB  - The products of the trithorax gene are required to stably maintain homeotic gene
      expression patterns established during embryo-genesis by the action of the
      transiently expressed segmentation genes. We have determined the intron/exon
      structure of the trx gene and the large alternatively spliced trx RNAs, which are
      capable of encoding only two protein isoforms. These very large trx proteins
      differ only in a long Ser- and Gly-rich N-terminal extension, encoded by exon II,
      which is present only in the larger trx isoform. We have identified a novel
      variant of the highly conserved nuclear receptor type of DNA binding domain. We
      have found that the previously identified Cys-rich central region contains
      multiple novel zinc finger motifs which are also present in the Polycomb-like
      protein and RBP2, a retinoblastoma binding protein. The trx proteins terminate
      with another novel conserved domain which we have identified in proteins from
      three kingdoms, including plants and fungi, indicating that has an ancient
      origin. Many of these proteins are chromosomally associated, suggesting that this
      domain may be involved in interactions between trx and other highly conserved
      components of chromatin involved in transcription regulation. The sequence
      alterations of trx mutations identify the highly conserved regions of trx as
      critical for the function of these large proteins. We show that zygotically
      expressed trx RNAs encoding the larger protein isoform are initially expressed in
      a spatially restricted pattern which overlaps the expression domains of the BX-C
      genes Ubx, abd-A and Abd-B. This pattern is transient and evolves into a broader
      expression domain encompassing the entire germ band during the extended germ band
      stage.

PMID- 8541211
TI  - The extra sex combs protein is highly conserved between Drosophila virilis and
      Drosophila melanogaster.
AB  - Extra sex combs (esc) is one of the Polycomb Group genes, whose products are
      required for long term maintenance of the spatially restricted domains of
      homeotic gene expression initially established by the products of the
      segmentation genes. We recently showed that the esc protein contains five copies
      of the WD motif, which in other proteins has been directly implicated in protein
      protein interactions. Mutations affecting the WD repeats of the esc protein
      indicate that they are essential for its function as a repressor of the homeotic
      genes. We proposed that they may mediate interactions between esc and other
      Polycomb Group proteins, recruiting them to their target genes, perhaps by
      additional interactions with transiently expressed repressors such as hunchback.
      To further investigate the functional importance of the WD motifs and identify
      other functionally important regions of the esc protein, we have begun to
      determine its evolutionary conservation by characterizing the esc gene from
      Drosophila virilis, a distantly related Drosophila species. We show that the esc
      protein is highly conserved between these species, particularly its WD motifs.
      Their high degree of conservation, particularly at positions which are not
      conserved in the WD consensus derived from alignment of all known WD motifs,
      suggests that each of the WD repeats in the esc protein is functionally
      specialized and that this specialization has been highly conserved during
      evolution. Its highly charged N-terminus exhibits the greatest divergence, but
      even these differences are conservative of its predicted physical properties.
      These observations suggest that the esc protein is functionally compact, nearly
      every residue making an important contribution to its function.

PMID- 8541212
TI  - A novel vertebrate svp-related nuclear receptor is expressed as a step gradient
      in developing rhombomeres and is affected by retinoic acid.
AB  - The protein encoded by the zebrafish gene svp[40] belongs to a distinct group
      within the steroid hormone receptor superfamily that includes Drosophila seven-up
      and several vertebrate orphan receptors. Svp[40] shares a particularly high
      degree of amino acid sequence identity (approximately 86%) with the mammalian
      transcription factors ARP-1 and COUP. The gene is expressed in specific regional
      and segmental domains within the developing brain. Correspondence between this
      expression pattern and early sites of neuronal differentiation and axonogenesis
      in the rostral brain may reflect an involvement in neural patterning. During the
      early embryonic stages when hindbrain rhombomeres are formed, a segmental
      expression pattern is established as a step gradient. The single steps of this
      gradient coincide directly with the four anteriormost segments suggesting a role
      in controlling rhombomere-specific expression of genes contributing to cell
      differentiation in the hindbrain. Since COUP/ARP-1 and retinoic acid receptors
      (RARs/RXRs) are known to have similar DNA-binding specificities, different levels
      of Svp[40] might modulate retinoid signaling through competition for binding to
      specific RAREs in the promoters of target genes. Treatment of zebrafish embryos
      with retinoic acid affects the svp[40] step gradient and causes an elimination of
      a regional expression domain in the retina. These observations are consistent
      with svp[40] being an integral part of the retinoid signaling network during
      hindbrain and eye development.

PMID- 8541213
TI  - Morphogenesis of Drosophila pupal wings in vitro.
AB  - We have developed an in vitro culture system which supports the differentiation
      of Drosophila pupal wings. Cultured wings develop marginal bristles and wing
      veins, and wing cells form a single prehair at their distal vertex at the
      appropriate developmental stages. We have tested two molecules with well defined
      activities to determine the usefulness of this system for applying
      pharmacological approaches to wing differentiation. Cycloheximide (CY) is a small
      molecule which inhibits protein synthesis. We found that 50 nM CY rapidly blocks
      all stages of wing differentiation without lowering cell viability. Chitinase is
      an enzyme which cleaves chitin polymers and is involved in normal cuticle
      apolysis. Chitinase applied prior to 28 h apf caused a contraction of the wing
      without affecting the general wing pattern. We have detected connections between
      the epithelium and pupal cuticle that are presumably targets of chitinase and are
      necessary for maintaining normal tissue shape during morphogenesis. Later in
      development exposure to chitinase caused a loss of normal prehair and bristle
      polarity, and high doses resulted in a severe disruption of the actin
      cytoskeleton.

PMID- 8541214
TI  - The expression pattern of the Distal-less homeobox-containing gene Dlx-5 in the
      developing chick limb bud suggests its involvement in apical ectodermal ridge
      activity, pattern formation, and cartilage differentiation.
AB  - Here we report the isolation from a chick limb bud cDNA library of a cDNA that
      contains the full coding sequence of chicken Dlx-5, a member of the Distal-less
      (Dlx) family of homeobox-containing genes that encode homeodomains highly similar
      to that of the Drosophila Distal-less gene, a gene that is required for limb
      development in the Drosophila embryo. The expression pattern of Dlx-5 in the
      developing chick limb bud suggests that it may be involved in several aspects of
      limb morphogenesis. Dlx-5 is expressed in the apical ectodermal ridge (AER) which
      directs the outgrowth and patterning of underlying limb mesoderm. During early
      limb development Dlx-5 is also expressed in the mesoderm at the anterior margin
      of the limb bud and in a discrete group of mesodermal cells at the mid-proximal
      posterior margin that corresponds to the posterior necrotic zone. These
      mesodermal domains of Dlx-5 expression roughly correspond to the anterior and
      posterior boundaries of the progress zone, the group of highly proliferating
      undifferentiated mesodermal cells underneath the AER that will give rise to the
      skeletal elements of the limb and associated structures. The AER and anterior and
      posterior mesodermal domains of Dlx-5 expression are regions in which the
      homeobox-containing gene Msx-2 is also highly expressed, suggesting that Dlx-5
      and Msx-2 might be involved in regulatory networks that control AER activity and
      demarcate the progress zone. In addition, Dlx-5 is expressed in high amounts by
      the differentiating cartilaginous skeletal elements of the limb, suggesting it
      may be involved in regulating the onset of limb cartilage differentiation.

PMID- 8541215
TI  - Breathless, a Drosophila FGF receptor homolog, is required for the onset of
      tracheal cell migration and tracheole formation.
AB  - Breathless, a Drosophila FGF receptor homolog (DFGF-R1), was shown to be
      essential for the migration of the tracheal cells and the posterior midline glia
      cells. The temporal requirement for the activity of this receptor was dissected
      by a dominant-negative construct lacking a functional cytoplasmic tyrosine-kinase
      domain. Induction of the construct prior to the onset of tracheal or glial cell
      migration produced phenotypes that were similar to those observed in the
      corresponding tissues of breathless null mutant embryos. However, this effect is
      not detected if the dominant-negative receptor is induced after the initiation of
      tracheal cell migration, indicating that Breathless is required primarily at the
      onset of the migration process. Induction of the construct after the tracheal
      branches are completed, blocked the formation of tracheoles, i.e. extension of
      cellular processes by the terminal tracheal cells, demonstrating that Breathless
      plays an essential role in this process as well. The requirement for Breathless
      at the onset of migration and the diversity of processes in which it
      participates, suggest that the receptor is involved in triggering transcription
      factors, which may be distinct for each context.

PMID- 8541216
TI  - Restricted expression of type-II TGF beta receptor in murine embryonic
      development suggests a central role in tissue modeling and CNS patterning.
AB  - The type-II TGF beta receptor mediates many of the biological responses to TGF
      beta. An examination of the expression of the type-II TGF beta receptor during
      mouse embryogenesis therefore provides specific information about the role of TGF
      beta during embryogenesis than has been available to date. We have isolated the
      genomic murine homologue of the human type-II TGF beta receptor corresponding to
      exon 2. The murine and human sequences show a high degree of homology. Using the
      murine probe, we found that type-II TGF beta receptor expression is regulated in
      both a spatial and a temporal fashion by using in situ hybridization and
      ribonuclease protection assays. Type-II TGF beta receptor expression is localized
      to the mesenchyme during critical interactions with adjacent epithelium such as
      developing hair follicles, whisker follicles and tooth anlage. In the central
      nervous system, type-II TGF beta receptor expression is highly restricted to the
      floor plate. Strong expression is also detected in migrating neural crest cells,
      meninges, and choroid plexus. Specific mesenchymal localization of type-II TGF
      beta receptor is also observed in lung, kidney, intestine, stomach, and bladder.
      The restricted expression of type-II TGF beta receptor in mesenchymal cells at
      sites of epithelial-mesenchymal interactions suggests that type-II TGF beta
      receptor plays a major role in mediating the establishment of embryonic organ
      systems. The highly restricted expression of type-II TGF beta receptor in the
      developing CNS suggests an important role for a serine/threonine kinase in
      patterning of the nervous system.

PMID- 8541217
TI  - Malformations of the heart, kidney, palate, and skeleton in alpha-MHC-Hoxb-7
      transgenic mice.
AB  - To begin to define the genetic network involved in cardiogenesis, we generated
      mice bearing the alpha-myosin heavy chain (MHC)-Hoxb-7 transgene. We hypothesized
      that using the cardiac-specific alpha-MHC promoter, we can direct ectopic
      expression of Hoxb-7 in the heart and perturb its normal development. Both whole
      mount in situ hybridization and northern analyses showed that this alpha-MHC
      promoter resulted in transgene expression in the developing heart. Severe
      ventricular septal defects (VSD) were found in several mutant mice.
      Interestingly, transgenic mice were observed to have other malformations as well,
      including cleft palate, renal anomalies, and skeletal abnormalities in the
      craniocervical and costosternal regions. The kidney defect consisted of double
      ureter and pelvis. In summary, we have shown that a dominant gain-of-function
      mutation of Hoxb-7 using the murine alpha-MHC promoter results in perturbation of
      the genetic circuitry underlying multiple developmental processes, including
      cardiogenesis. Misexpression of Hoxb-7 during heart development may be involved
      in the pathogenesis of VSD.

PMID- 8541218
TI  - Two forms of Xenopus nuclear factor 7 have overlapping spatial but different
      temporal patterns of expression during development.
AB  - Xenopus nuclear factor 7 (xnf7) is a maternal gene product that functions in the
      determination of the dorsal-ventral body axis. We have cloned two xnf7 cDNAs,
      xnf7-O and xnf7-B, that have a different temporal pattern of expression. The
      cDNAs differ by 39 amino acid residues scattered throughout the molecule. Most of
      the changes were conservative in nature. Using gene specific probes we found that
      xnf7-O transcripts were abundant in oocytes and decreased until the neurula
      stage, after which they increased in abundance. Xnf7-B transcripts were in low
      abundance in oocytes and were expressed at high levels at the neurula stage and
      in adult brain. Both xnf7-O and xnf7-B transcripts at the neurula stage were
      localized in the dorsal region of the embryo, including the neural folds and
      somites. Xnf7 was not expressed in ventralized embryos that lacked dorsal
      structures, thereby substantiating its dorsal localization in the embryo. The
      promoter region of the xnf7-O gene does not possess a TATA box but does contain
      E2F, USF, Sp1-like and AP1 binding sites within the first 421 bp from the
      transcription initiation site. A 62 bp fragment of the xnf7-O promoter containing
      the Sp1-like and E2F sites can direct proper spatial expression of a transgene in
      embryos.

PMID- 8541219
TI  - Embryo brain kinase: a novel gene of the eph/elk receptor tyrosine kinase family.
AB  - A new gene belonging to the Eph/Eck/Elk receptor tyrosine kinase family has been
      cloned from mouse brain. The gene maps to mouse chromosome 4. In the adult brain
      it is expressed exclusively and abundantly in the hippocampus. We propose to name
      it Ebk (embryo brain kinase), as in situ hybridisation shows expression in many
      parts of the developing mouse brain. The most abundant expression is in the
      subcommissural organ, and the earliest expression is in the forebrain neural
      folds, in rhombomeres 2-6, and in somites and heart. Other regions positive at
      various stages include the cochlear duct, trigeminal ganglion, lung, first
      branchial arch, and tooth primordia. Also positive are areas of mesenchyme
      underlying various epithelia during morphogenesis, especially in the mouth and
      nose, as well as in the eyelids and toes. We compare these patterns with the
      available data on the 12 other known members of this gene family. Most of them,
      like Ebk, are expressed in brain (especially adult hippocampus and embryonic
      rhombomeres) and in organs rich in epithelia (especially lung), although the
      spatial and temporal patterns differ. We suggest that combinatorial patterns of
      these receptors act as labels for the regional identity of neurons and epithelia,
      and could mediate fine control of neurite pathfinding and epithelial
      morphogenesis.

PMID- 8541220
TI  - Regulation of polyhomeotic transcription may involve local changes in chromatin
      activity in Drosophila.
AB  - The polyhomeotic (ph) gene of Drosophila is a member of the Polycomb group of
      genes and encodes a chromatin protein required for negative regulation of
      homeotic genes and other loci, in particular the ph locus itself. We have studied
      the genetic control of ph transcription during development. Early ph expression
      is under the control of bicoid and engrailed as activators and of oskar as an
      inhibitor. The negative autoregulation of ph starts at the blastoderm stage and
      is partly mediated by a transvection effect. As the number of functional copies
      of ph increases in the same genome, a concomitant reduction of the transcription
      of each copy is observed. This regulation is ensured, likely at the chromatin
      level, positively by the trithorax group and negatively by the Polycomb group
      gene products like a homeotic gene, but it occurs in the same cells. We propose
      that an equilibrium between these two states of chromatin activity ensures an
      accurate level of ph transcription.

PMID- 8541221
TI  - Bone morphogenetic protein 2 in the early development of Xenopus laevis.
AB  - The temporal and spatial transcription patterns of the Xenopus laevis Bone
      morphogenetic protein 2 (BMP-2) gene have been investigated. Unlike the closely
      related BMP-4 gene, the BMP-2 gene is strongly transcribed during oogenesis.
      Besides some enrichment within the animal half, maternal BMP-2 transcripts are
      ubiquitously distributed in the early cleavage stage embryos but rapidly decline
      during gastrulation. Zygotic transcription of this gene starts during early
      neurulation and transcripts are subsequently localized to neural crest cells,
      olfactory placodes, pineal body and heart anlage. Microinjection of BMP-2 RNA
      into the two dorsal blastomeres of 4-cell stage embryos leads to ventralization
      of developing embryos. This coincides with a decrease of transcripts from dorsal
      marker genes (beta-tubulin, alpha-actin) but not from ventral marker genes (alpha
      globin). BMP-2 overexpression inhibits transcription of the early response gene
      XFD-1, a fork head/HNF-3 related transcription factor expressed in the dorsal
      lip, but stimulates transcription of the posterior/ventral marker gene Xhox3, a
      member of the helix-turn-helix family. Activin A incubated animal caps from BMP-2
      RNA injected embryos show transcription of ventral but an inhibition of dorsal
      marker genes; thus, BMP-2 overrides the dorsalizing activity of activin A. The
      results demonstrate that BMP-2 overexpression exerts very similar effects as have
      previously been described for BMP-4, and they suggest that BMP-2 may act already
      as a maternal factor in ventral mesoderm formation.

PMID- 8541222
TI  - Distinct temporal expression of mouse Nkx-5.1 and Nkx-5.2 homeobox genes during
      brain and ear development.
AB  - The mouse Nkx-5.1 and Nkx-5.2 genes have been identified by sequence homology to
      Drosophila NK genes within the homeobox domain. Here, we report the isolation of
      the Nkx-5.2 cDNA and a detailed comparative analysis of the spatio-temporal
      expression patterns for Nkx-5.1 and Nkx-5.2 genes. Nkx-5.2 transcripts are first
      detected in E13.5 embryos where they colocalize with Nkx-5.1 mRNA in the
      developing central nervous system and the inner ear. However, the onset of Nkx
      5.1 transcription begins much earlier in 10 somite stage embryos (E8.5) in the
      otic placode and the branchial region. Nkx-5.1 expression in the ear persists
      until birth, whereas in branchial arches it is transient between E8.5 to E11.5.
      Transcript distribution appears regionalized in the otic vesicle concentrating at
      the anterior and posterior margin and later at the dorsal side of the otocyst.
      These domains are distinct from regions expressing Pax-2 and sek, two other early
      markers for otic development. From E11.5 to birth several Nkx-5.1 expression
      domains appear in the brain between the ventral diencephalon and the
      myelencephalon. The same expression domains also exist for Nkx-5.2 beginning at
      E13.5. The regionally restricted expression pattern of both Nkx-5 genes during
      mouse development suggests their involvement in cell type specification of
      neuronal cells.

PMID- 8541223
TI  - A novel gene expressed during zebrafish gastrulation identified by differential
      RNA display.
AB  - Vertebrate gastrulation is a dynamic period of development characterized by
      extensive cell migrations. This stage of development is likely to require the
      expression of a new genetic repertoire to initiate and direct these dramatic
      changes. The differential RNA display has been used to identify genes
      specifically expressed during the gastrula stage of a model vertebrate, the
      zebrafish. One of the genes isolated by the differential display technique has
      been sequenced and characterized for its spatial and temporal expression. This
      gene, called G12, is expressed during a narrow window of time during gastrulation
      and is restricted to a single cell type. At this time of development the
      zebrafish embryo consists of three cell types: the yolk cell, EVL cells and deep
      cells. Interestingly, both EVL and deep cells derive early in development from
      common progenitor cells but G12 expression is restricted only to the EVL lineage.
      Comparison of the amino acid sequence from this gene with the Genbank database
      indicates similarity to two previously reported mammalian genes. The similarity
      between these three genes suggests that they may serve a common function. The G12
      gene is the first example of restricted gene expression in EVL cells of the
      zebrafish. The G12 gene should prove to be a useful model for the study of
      regulated gene expression during gastrulation.

PMID- 8541224
TI  - SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth
      resistant to estrogen and antiestrogens.
AB  - Estrogen receptor positive ovarian cancer is often refractile to antiestrogen
      therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in
      vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3
      cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the
      estrogen responsive T47D breast carcinoma cell line, their growth was not
      responsive to estradiol (E2) and was not inhibited by the antiestrogens OH
      tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to
      apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE
      driven reporter gene, and E2 stimulation of expression of the early growth
      response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression
      of the progesterone receptor gene (PR) even after addition of E2, and the protein
      products of the estrogen responsive genes HER-2/neu and cathepsin D were
      expressed at constitutive levels that were not regulated by E2. Therefore,
      estrogen resistance in these cells may be a result of constitutive expression and
      loss of E2 regulation of selected growth regulatory gene products rather than a
      defect in estrogen activation of ER as a transcriptional regulator.

PMID- 8541226
TI  - Estradiol and testosterone in specific regions of the human female brain in
      different endocrine states.
AB  - Post-mortem concentrations of estradiol and testosterone were measured in 17
      brain areas, serum and fat in 6 fertile and 5 postmenopausal women. Steroid
      concentrations were measured with radioimmunoassay after extraction of brain
      tissue with ethanol and purification with celite chromatography. There were
      regional differences in brain concentrations of both steroids. The highest levels
      of estradiol and testosterone were noted in the hypothalamus, preoptic area and
      substantia nigra. These findings may assist in the interpretation of functional
      animal studies where the hypothalamus-preoptic area and the nigrostriatal
      dopamine system have proved to be target areas for estradiol. When compared to
      postmenopausal women, estradiol concentrations were significantly higher in the
      brains of fertile women, which indicates that peripheral serum levels of
      estradiol are reflected in the brain. This study has yielded information about
      steroid levels in different endocrine states and could provide a frame of
      reference for studies of estradiol and testosterone mediated effects on the
      central nervous system.

PMID- 8541225
TI  - Cytotoxic actions of cytokines on cultured mouse luteal cells are independent of
      nitric oxide.
AB  - We investigated the cytotoxic effects of various cytokines secreted by
      macrophages or T lymphocytes on luteal cells, and the role of nitric oxide (NO)
      produced by luteal cells in cytotoxic actions of cytokines. Mouse luteal cells
      were cultured in serum-free medium with interferon-gamma (IFN-gamma), tumor
      necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta) alone, or
      with various combinations of these cytokines for 6 days. Cytotoxic actions of
      cytokines and NO production by luteal cells were evaluated by number of viable
      cells and the amount of nitrite and nitrate (stable metabolites of NO) in medium,
      respectively. IFN-gamma (1000 U/ml), TNF-alpha (3000 U/ml), or IL-1 beta (30
      U/ml) alone, and the combination of TFN-alpha and IL-1 beta (10 U/ml) did not
      decrease number of viable cells and was without effects on NO production. The
      combination of IFN-gamma and IL-1 beta (10 U/ml) also did not decrease the number
      of viable cells, while it increased NO production a little but significantly.
      Combinations of INF-gamma and TNF-alpha, and IFN-gamma, TNF-alpha and IL-1 beta
      (10 U/ml) markedly decreased number of viable cells. The combination of IFN-gamma
      and TNF-alpha increased NO production a little but significantly, and the
      combination of three cytokines (IFN-gamma, TNF-alpha, and IL-1 beta) caused a
      greater increase in NO production. An NO synthase inhibitor, L-NG-monomethy-L
      arginine (0.5 mM) or aminoguanidine (0.5 mM) abolished increases in NO production
      induced by combinations of IFN-gamma and TNF-alpha, and IFN-gamma, TNF-alpha and
      IL-1 beta completely without effects on number of viable cells. The present
      results indicate that combinations of cytokines including IFN-gamma and TNF-alpha
      induce death of cultured mouse luteal cells, and that the cytotoxic actions of
      these cytokines are independent of NO production by luteal cells.

PMID- 8541227
TI  - Identification of phosphorylation sites in the mouse oestrogen receptor.
AB  - Phosphorylation sites in the mouse oestrogen receptor, expressed in COS-1 cells
      in the presence of 17 beta-oestradiol, have been mapped by solid phase
      microsequencing. The receptor was first radio-labelled with [32P]orthophosphate
      and a number of 3H- or 14C-labelled amino acids, immunopurified and then tryptic
      peptides were separated by thin layer chromatography or high performance liquid
      chromatography. Amino acid sequence analysis indicated that Ser-122, Ser-156, Ser
      158 and Ser-298 were phosphorylated. The substitution of Ser-122 and Ser-298 with
      alanine had a negligible effect on the transcriptional activity of the receptor
      in transfected cells. However, a reduction of transcriptional activity was
      observed when Ser-122 was mutated in the context of mutations in a putative
      amphipathic alpha-helix involved in AF-2 activity. Thus a region of AF-1 that
      encompasses Ser-122 appears to interact with AF-2 in the full-length receptor.

PMID- 8541228
TI  - Characterization of the promoter of the gene for a mouse vas deferens protein
      related to the aldo-keto reductase superfamily: effect of steroid hormones and
      phorbol esters.
AB  - Mouse vas deferens protein (MVDP) is a member of the aldo-keto reductase family
      regulated by androgens. The expression of a hybrid gene containing the promoter
      of the MVDP gene and the chloramphenicol acetyl transferase (CAT) gene coding
      region was analyzed in two cell lines that do not normally express the MVDP gene:
      T47D and CV1 cells. A small region of the promoter (-121 to +41) was able to
      direct significant expression of the reporter gene in both cell lines. Additional
      elements, between -510 and -121 modulate basal expression in a cell-dependent
      manner. Interestingly, the 162 bp fragment serves as an androgen-dependent
      enhancer, and mutation of the consensus ARE sequence located between positions 
      111 and -97 resulted in a loss of androgen response in both cell lines.
      Additional elements, upstream of the enhancer, modulate induction positively or
      negatively in relation to the cell line used. The expression of different MVDP
      CAT constructs was more effectively induced by androgens than by glucocorticoids
      at physiological hormonal concentrations. In addition to the 162 bp enhancer,
      sequences upstream of -510 were also required for specific androgen regulation.
      Phorbol 12-myristate 13-acetate (TPA) had no effect on basal activity of the 1.8
      kb MVDP-CAT construct but strongly enhanced the induction by androgens.

PMID- 8541229
TI  - Estrogen receptor blockade by the pure antiestrogen, ZM 182780, induces death of
      pituitary tumour cells.
AB  - Our previous studies have shown that even in the absence of estrogen, the
      estrogen receptor (ER) is still involved in growth by way of its conversion to a
      transcriptionally active state by growth inducing cytokines. The following paper
      now provides evidence that under more physiological conditions, the ER within the
      GH3 cell line used for the previous investigations, not only controls growth, but
      that transcriptional activity of the receptor is required for cell survival.
      Therefore when GH3 cells, maintained under serum and steroid replete conditions,
      are exposed to the pure antiestrogen ZM 182780 (10 nM), marked cell death is
      observed 72-120 h after first exposure. Studies on the nature of this cell death
      suggested that it had some of the reported characteristics of apoptosis or
      programmed cell death. Removal of steroids from the culture medium also resulted
      in cell death and this was enhanced by the addition of the pure antiestrogen.
      Both steroid withdrawal and ZM 182780 induced cell death was completely reversed
      by the inclusion of estrogens in the steroid free culture medium. In contrast,
      the non-steroidal antiestrogen, 4-hydroxytamoxifen (4-OHT) was not able to
      enhance steroid withdrawal death and at 1 microM, this compound was shown to have
      marked ER agonist activity. Further studies on the addition of conditioned medium
      from high density GH3 cell cultures, to low density steroid free cells, strongly
      suggested that the ER within these cells was responsible for the production of
      autocrine/paracrine survival factors.

PMID- 8541231
TI  - Blockade of estrogen synthesis with an aromatase inhibitor affects luteal
      function of the pseudopregnant rat.
AB  - The luteotropic action of estrogen (E) was investigated using immature
      pseudopregnant rat as the model and CGS 16949A (Fadrozole hydrochloride), a
      potent aromatase inhibitor (AI), to block E synthesis. Aromatase activity could
      be inhibited by administering CGS 16949A (50 micrograms/day/rat) via a mini
      osmotic Alzet pump (model 2002) for 3 days during pseudopregnancy. This resulted
      in significant reduction of serum (40%, P < 0.05) and intraovarian 70.6%, P <
      0.001) estradiol-17 beta (E2) levels. The serum and intraovarian progesterone
      (P4) levels as analyzed on day 4 of pseudopregnancy were also reduced by > or =
      50% (for both, P < 0.01). Simultaneous administration of estradiol-3-benzoate
      (E2B) via an Alzet pump during the AI treatment period at a dose of 1
      microgram/day could completely reverse the AI induced reduction in P4 secretion.
      The luteal cells of experimental rats depleted of E in vivo showed a
      significantly reduced response upon incubation with hCG or dbcAMP in vitro (P <
      0.05 and 0.001, respectively). Addition of E2 (500 pg/tube) at the time of in
      vitro incubation was able to partially increase the responsiveness to hCG. The
      luteal cell LH/hCG receptor content and the affinity of hCG binding to the
      receptor remained unchanged following AI treatment in vivo. Both esterified and
      total cholesterol content of luteal cells of rats treated with AI in vivo was
      significantly high (P < 0.05) suggesting that E lack results in an impairment in
      cholesterol utilization for steroidogenesis. The results clearly show that E
      regulates luteal function in the pseudopregnant rat by acting at a non-cAMP
      mediated event and this perhaps involves facilitation of cholesterol utilization
      at the mitochondrial level for P4 synthesis.

PMID- 8541230
TI  - Differential effects of 1,25-dihydroxyvitamin D3-analogs on osteoblast-like cells
      and on in vitro bone resorption.
AB  - Although numerous studies have shown potent antiproliferative and differentiation
      inducing effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and its analogs on
      cells not directly related to bone metabolism, only few reports focussed on the
      effects of these analogs on bone. We compared the action of several recently
      developed analogs with that of 1,25-(OH)2D3 on human (MG-63) and rat (ROS 17/2.8)
      osteoblast-like cells and on in vitro bone resorption. In MG-63 cells the analogs
      EB1089 and KH1060 were about 166,000 and 14,000 times more potent than 1,25
      (OH)2D3 in stimulating type I procollagen and 100 and 6,000 times more potent in
      stimulating osteocalcin production, respectively. Also in ROS 17/2.8 cells EB1089
      and KH1060 were most potent in inducing osteocalcin synthesis. In vitro bone
      resorption was 2.3 and 17.5 times more potently stimulated by EB1089 and KH1060,
      respectively. In MG-63 cells, 1,25-(OH)2D3 and the analogs inhibited cell
      proliferation, whereas both 1,25-(OH)2D3 and the analogs stimulated the growth of
      ROS 17/2.8 cells. Differences in potency could neither be explained by affinity
      for the vitamin D receptor nor by a differential involvement of protein kinase C
      in the action of the analogs. Together, these data show that also in bone the
      analogs EB1089 and KH1060 are more potent than 1,25-(OH)2D3 but that the potency
      of the analogs compared to 1,25-(OH)2D3 is dependent on the biological response.
      On the basis of these observations it can be concluded that the reported reduced
      calcemic effect in vivo is not the result of a decreased responsiveness of bone
      to these analogs. Lastly, in view of eventual clinical application of 1,25
      (OH)2D3-analogs, the observed stimulation of in vitro bone resorption and growth
      of an osteosarcoma cell line warrant in vivo studies to further examine these
      effects.

PMID- 8541232
TI  - Specificity of glucuronosyltransferase activity in the human cancer cell line
      LNCaP, evidence for the presence of at least two glucuronosyltransferase enzymes.
AB  - Recent findings obtained by our group showed that incubation of LNCaP cells with
      labeled steroids leads to the formation of 3- and 17-hydroxysteroid glucuronides.
      In this study, the specificity and the kinetic properties of 3-hydroxy-C19steroid
      uridine diphospho-glucuronosyltransferase (3-OH-UGT) and 17-hydroxy-C19steroid
      UGT (17-OH-UGT) activities in LNCaP cells were investigated. Results indicate
      that the UGT has a high affinity for testosterone, dihydrotestosterone (DHT),
      androsterone (ADT) and androstane-3 alpha, 17 beta-diol (3 alpha-DIOL), with Km
      values ranging from 0.25 to 0.68 microM. The Km values are approx. 10-fold higher
      for androst-5-ene-3 beta,17 beta-diol (5-ene-DIOL) and androstane-3 beta,17 beta
      diol (3 beta-DIOL). The relative specificities (Vmax/Km) also showed higher
      turnover rates for testosterone, DHT, ADT and 3 alpha-DIOL with values ranging
      from 2.93 to 5.71, than for 3 beta-DIOL and 5-ene-DIOL with ratios of 0.41 and
      1.10, respectively. Dixon plot and Cornish-Bowden analysis demonstrate that
      testosterone, DHT, ADT, and 3 alpha-DIOL inhibit the glucuronidation of DHT and
      ADT in a competitive fashion. In contrast, when the studies are performed with 3
      beta-diol and 5-ene-DIOL the inhibition of ADT glucuronidation is uncompetitive
      while the glucuronidation of DHT is inhibited competitively, suggesting the
      presence of two UGT enzymes, one for glucuronidation of the 17 beta-OH group and
      a second for the 3 alpha-OH group. Further evidence for the presence of two UGTs
      in LNCaP cells was obtained by incubation with a variety of 3 beta-OH-C19
      steroids which caused a marked inhibition of DHT-G formation but had no effect on
      the glucuronidation of ADT. In summary, our data demonstrate the presence of at
      least two UGTs in the human prostate cancer cell line LNCaP. The relative
      specificity of the 17-OH-UGT in LNCaP cells is 3 alpha-DIOL > DHT > testosterone,
      while ADT is glucuronidated by the 3-OH-UGT.

PMID- 8541233
TI  - Identification of estrogen regulated genes in Fe33 rat hepatoma cells by
      differential display polymerase chain reaction and their hormonal regulation in
      rat liver and uterus.
AB  - We applied the differential display RT-PCR (ddRT-PCR) technology to identify
      estrogen-regulated hepatic genes in the estrogen receptor expressing rat hepatoma
      cell line Fe33. Three genes of known sequences were detected by the ddRT-PCR
      approach: IGF binding protein-1 (IGFBP-1), vitamin D-dependent calcium-binding
      protein (CaBP9k) and major acute phase protein (MAP). Effects of ethinyl
      estradiol on the mRNA levels of these genes were confirmed by "Northern-blot"
      analysis. If given in combination with dexamethasone and glucagon, ethinyl
      estradiol caused 40-, 15- and 11-fold increases in the mRNA steady state level of
      IGFBP-1, CaBP9k and MAP, respectively, in Fe33 cells 24 h after addition of
      hormone. Besides ethinyl estradiol, the partial estrogen agonist OH-tamoxifen
      caused dose dependent effects on expression of MAP and IGFBP-1. Estrogen
      regulation of the respective genes and the modulatory effects of progesterone (10
      mg/animal/day) were studied in ovariectomized rats treated subcutaneously for 14
      days with 1 microgram/animal/day estradiol. "Northern-blot" analysis of liver RNA
      revealed a 6-fold stimulation of IGFBP-1 mRNA levels in estradiol-treated
      compared to vehicle-treated rats and a weak but detectable increase of MAP mRNA
      steady state level (1.6-fold) upon estradiol administration. No effect of
      estradiol treatment could be monitored for CaBP9k in rat liver. Modulatory
      effects of progesterone on estradiol-stimulated expression in the liver could be
      monitored for IGFBP-1 only. In an extension of our investigation on the
      expression of the three genes in rat liver, we determined their expression and
      hormonal regulation in the uterus of the same animals. In the uterus, estradiol
      caused an increase in CaBP9k mRNA. In contrast, IGFBP-1 mRNA levels increased
      dramatically upon progesterone administration, whereas no effect of estradiol
      treatment could be detected. MAP mRNA levels increased only after
      coadministration of estradiol and progesterone. In conclusion, the ddRT-PCR
      proved to be a powerful method to identify estrogen-regulated genes. The study on
      the hormonal regulation of three genes stimulated by estrogen in Fe33 cells
      revealed similarities and differences in their regulation in vivo and in vitro.

PMID- 8541234
TI  - Testosterone metabolism in primary cultures of human prostate epithelial cells
      and fibroblasts.
AB  - We compare testosterone (T) metabolism in primary cultures of epithelial cells
      and fibroblasts separated from benign prostate hypertrophy (BPH) and prostate
      cancer tissues. In all cultures, androstenedione (delta 4) formed by oxidation of
      T by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) represented 80% of the
      metabolites recovered. The amounts of 5 alpha-dihydrotestosterone (DHT), formed
      by reduction of T by 5 alpha-reductase (5 alpha-R), were small: 5 and 2% (BPH)
      and 8 and 15% (adenocarcinoma) for epithelial cells and fibroblasts,
      respectively. Northern blot analysis of total RNA from epithelial cells (BPH or
      adenocarcinoma) attributed the reductive activity to the 5 alpha-reductase type 1
      isozyme and oxidative activity to the 17 beta-HSD type 2. In cancer fibroblasts,
      only little 17 beta-HSD type 2 mRNA was detected. The 5 alpha-reductase
      inhibitors, 4-MA (17 beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5 alpha-androstan
      3-one) and finasteride, inhibited DHT formation with a preferential action of 4
      MA on epithelial cells (BPH or adenocarcinoma) and of finasteride on fibroblasts
      from adenocarcinoma. Neither inhibitor acted on delta 4 formation. On the other
      hand, the lipido-sterol extract of Serenoa repens (LSESr, Permixon) inhibited the
      formation of all the T metabolites studied [IC50 S = 40 and 200 micrograms/ml
      (BPH) and 90 and 70 micrograms/ml (adenocarcinoma) in epithelial cells and
      fibroblasts, respectively]. These results have important therapeutic implications
      when selecting appropriate treatment options for BPH.

PMID- 8541235
TI  - Dual regulation of luteal progesterone production by androstenedione during
      spontaneous and RU486-induced luteolysis in pregnant rats.
AB  - The effect of androstenedione on luteal progesterone production was studied
      during luteolysis preceding parturition as well as that induced by the
      antiprogestin RU486 in late pregnant rats. Luteal cells from animals on days 19,
      20 or 21 of pregnancy and incubated with 10 microM androstenedione increased
      progesterone production by 99, 136, and 277%, respectively. The animals receiving
      androstenedione (10 mg/rat s.c.) on day 19 of pregnancy showed an increase in
      serum progesterone levels, a decline in luteal 3 beta-hydroxysteroid
      dehydrogenase (3 beta-HSD) activity and an increase in corpus luteum weight
      without modifying 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity
      on day 21 of pregnancy. Androstenedione and testosterone but not
      dihydrotestosterone were able to prevent the decrease in serum progesterone
      concentration and corpus luteum weight observed 58 h after treatment with RU486
      (2 mg/kg) on day 18 of pregnancy. However, the three androgens studied inhibited
      the luteal 3 beta-HSD activity but 20 alpha-HSD activity was not affected, when
      compared with animals receiving RU486 alone. The co-administration of
      androstenedione with the aromatase inhibitor 4-hydroxyandrostenedione or with the
      specific antioestrogen ICI 164,384 did not modify the effects induced by
      androstenedione in RU486-treated rats, indicating that the action of
      androstenedione on progesterone production and secretion at the time of
      luteolysis seems to occur through an androgenic mechanism and is not mediated by
      previous conversion of the androgens to oestrogens. In all experiments the high
      luteal 20 alpha-HSD activity, that characterizes a luteolytic process, was not
      modified by androgens. Androstenedione administered to adrenalectomized rats was
      also able to prevent the decrease in serum progesterone concentration observed in
      spontaneous or RU486-induced luteolysis. The administration of androstenedione to
      RU486-treated rats induced a decrease in luteal progesterone content concomitant
      with an increase in serum progesterone levels. These studies demonstrate that
      androgens during luteolysis, are able to stimulate luteal progesterone secretion,
      prevent the loss in corpora lutea weight and enhance the decrease in 3 beta-HSD
      activity, without affecting the increase in 20 alpha-HSD activity.

PMID- 8541236
TI  - Sulfamates of various estrogens are prodrugs with increased systemic and reduced
      hepatic estrogenicity at oral application.
AB  - Oral therapy with natural or synthetic estrogens, like ethinylestradiol, suffers
      from low, suboptimally defined bioavailability and excess hepatic estrogen
      actions. N,N-alkylated and non-alkylated sulfamates of ethinylestradiol,
      estradiol and estrone overcome these deficiencies. Ovariectomized Wistar rats (n
      = 6-7/group) were orally treated for 7 days, and killed on day 8, plasma was
      gained on days 0, 4, and 8. Systemic estrogenicity was quantified by assessment
      of uterine weight, vaginal cornification, and measurement of gonadotropins by
      homologous RIA. Estrogenicity in the liver was analysed. Angiotensinogen was
      estimated by RIA of angiotensin-1 after incubation of EDTA-plasma with porcine
      renin. Total and high-density cholesterol were measured by enzymatic methods.
      Preliminary biotransformation studies were performed after oral administration of
      10 micrograms, 5 microCi [2,4,6,7-3H]estradiol sulfamate. Ethinylestradiol led to
      distinct elevation of angiotensin-1 and dramatic depression of cholesterol
      fractions, reflecting hepatic estrogen effects, already at doses with marginal
      systemic effects. Estradiol and estrone had systemic and hepatic estrogenic
      activity at much higher doses only. Estrogen sulfamates had systemic estrogen
      activity 10-90-fold above that of their parent estrogen. Non-alkylated sulfamates
      of given estrogens were more active than N-alkylated ones. Elevation of systemic
      estrogen activity was always combined with a dramatic reduction of hepatic
      estrogenicity. Estradiol sulfamate had a 90-fold elevated systemic estrogen
      activity vs estradiol, but lacked hepatic activity including the 30-fold dose
      inducing vaginal response. Three hours after administration no unchanged
      estradiol sulfamate was detectable in plasma. Rather peaks, probably representing
      estradiol and estrone, were found. Estrogen sulfamates are considered prodrugs of
      their parent estrogen, which do not interact with any liver function during the
      first-pass. They represent a new strategy of oral hormone administration. Their
      main potential seems to be the systemic generation of natural estrogens when used
      in oral contraceptives.

PMID- 8541237
TI  - Plasma levels of epitestosterone from prepuberty to adult life.
AB  - Epitestosterone has for a long time been considered as a biologically inactive
      steroid. However, recently a distinct antiandrogenic activity of this naturally
      occurring endogenous epimer of testosterone has been demonstrated.
      Epitestosterone plays a role in the control of doping with testosterone, since an
      arbitrary ratio of testosterone to epitestosterone in urine has been accepted as
      a marker for testosterone abuse. For this reason, its urinary excretion has been
      examined intensively by several authors. On the other hand, its concentration in
      the blood of men was reported only randomly in a few cases. In the present study
      the epitestosterone level in human plasma was determined by a specific
      radioimmunoassay and the concentration of epitestosterone was established in age
      groups of males of 6 to 65 years of age. There is a clear age dependence of
      epitestosterone plasma concentration in males. In young boys before puberty,
      antiandrogenic epitestosterone prevails over testosterone, in adults a striking
      decline of the ratio epitestosterone:testosterone can be observed.

PMID- 8541238
TI  - A sensitive assay for measurement of plasma estrone sulphate in patients on
      treatment with aromatase inhibitors.
AB  - A major obstacle to the understanding of the mechanisms of action of aromatase
      inhibitors in breast cancer is the observation that plasma estrogens are
      sustained at about 30-50% of their control levels despite 85-95% inhibition of
      the conversion of tracer androstenedione (A) to estrone (E1). The discrepancy
      could be due to lack of sensitivity of current RIAs. Due to low levels of plasma
      estradiol (E2) (mean about 20 pM) and E1 (mean about 75 pM) in postmenopausal
      women, it is difficult to develop RIA methods with the sensitivity required to
      detect > 90% suppression from baseline. In contrast, the plasma level of the
      estrogen conjugate estrone sulphate (E1S) is substantially higher (mean level
      about 400 pM). This paper describes a new assay to measure plasma E1S in the low
      range aiming to detect > 95% suppression of E1S from baseline values in patients
      treated with aromatase inhibitors. E1S was separated from unconjugated estrogens,
      hydrolysed and purified as unconjugated E1. E1 was subsequently reduced to E2,
      purified, and measured by a highly sensitive RIA using oestradiol-6-(O
      carboxymethyl) oximino-(2(-)[125I]iodohistamine as ligand. The sensitivity limit
      of the method was 2.7 pM. Patients on treatment with the aromatase inhibitors
      formestane or aminoglutethimide or both drugs in concert were found to have
      plasma levels of E1S ranging from 3 to 274 pM with a mean suppression of 78, 86
      and 95%, respectively, compared to baseline, a lower suppression than that
      reported in previous trials with these drugs.

PMID- 8541239
TI  - Tissue-dependent expression of a novel splice variant of the human oestrogen
      receptor.
AB  - We have isolated a novel splice variant of ER mRNA from normal endometrial tissue
      using RT/PCR. The variant contains an unusual splice junction formed by splicing
      sequences within exons 4 and 7 together. The translated protein product would be
      predicted to lack part of exon 4, all of exons 5 and 6 and, due to a missense
      alignment at the new splice junction, the remaining sequence from exon 7 would be
      translated out of frame and terminate at the exon 7/8 splice junction. As a
      result, the protein would lack most of the hormone binding domain (HBD) and the
      major oestrogen-dependent transactivating region (AF-2), but still contain the
      DNA binding domain (DNA-BD) and N-terminal transactivating region (AF-1). In
      contrast to the exon 5 deleted variant of ER (delta 5), which was expressed in
      both normal endometrium and liver, this novel variant was present in endometrium
      but not in liver samples. These results confirm that some ER splice variants are
      expressed in normal, non-malignant oestrogen responsive tissues. In addition,
      they demonstrate the tissue specific expression of a novel and interesting splice
      variant of ER in these normal tissues.

PMID- 8541240
TI  - Effects of two classes of progestagens, pregnane and 19-nortestosterone
      derivatives, on cell growth of human breast tumor cells: I. MCF-7 cell lines.
AB  - The effects of two classes of progestagens, e.g. pregnane [Org 2058,
      medroxyprogesterone acetate (MPA), R5020, progesterone (PROG)] and 19
      nortestosterone derived progestagens [3-ketodesogestrel (KDG), levonorgestrel
      (LNG), gestodene (GES), norethisterone (NE), Org 30659] on proliferation of three
      estradiol (E2)-dependent human breast tumor MCF-7 cell lines of different origin
      [Van der Burg (B), Litton bionetics (L) and McGrath (M)] were studied. The
      pregnane derivatives hardly stimulated cell growth at 10(-6) M in MCF-7 B and L
      cells except for Org 2058 in B cells, whereas in M cells a statistically
      significant growth induction was observed except for PROG. The 19-nortestosterone
      derivatives induced cell growth at doses at 10(-7) M or higher in all three cell
      lines. NE, GES and Org 30659 were more potent stimulators than KDG and LNG at 10(
      7) M. E2 already showed maximal stimulation at 10(-10) M. For all three cell
      lines, the effects and ranking of the individual progestagens were similar.
      Antiprogestagens, like RU 38486 and Org 31710 could not block these stimulatory
      effects while antiestrogens like 4-hydroxytamoxifen and ICI 164,384 could. This
      suggests that cell growth by the above-mentioned progestagens occurs via an
      interaction with the estrogen receptor. Indeed, displacement studies with cytosol
      from MCF-7 M cells revealed that at very high concentrations NE, GES and Org
      30659 were able to displace 50% of the radiolabelled E2, while KDG and LNG could
      not. Relative binding affinities (RBAs) were 0.010, 0.025 and 0.015% for NE, GES
      and Org 30659, respectively. The effect of the two classes of progestagens on
      cell proliferation was also investigated at several dose levels in combination
      with E2 (10(-10) M) in the MCF-7 B cell line. This resulted in a statistically
      significant inhibition of cell growth with R5020, MPA and most of the 19
      nortestosterone derivatives at concentrations of 10(-8) M. Org 2058 and NE did
      not have any influence on E2-induced growth. The inhibitory effects could not be
      blocked by antiprogestagens. In summary these studies with 3 subclones of MCF-7
      cells show that the pregnane derived progestagens stimulate growth only in one
      subclone, whereas the 19-nortestosterone derived progestagens do so in all three
      subclones. The progestagens possess estrogenic activity only at high
      pharmacological doses, being 10,000 times weaker than estradiol. In combination
      with estrogens most progestagens gave a reduction of E2-stimulated growth in the
      B subclone.

PMID- 8541241
TI  - Effects of two classes of progestagens, pregnane and 19-nortestosterone
      derivatives, on cell growth of human breast tumor cells: II. T47D cell lines.
AB  - Two classes of progestagens, e.g. pregnane [Org 2058, progesterone (PROG), R5020,
      medroxyprogesterone acetate (MPA)] and 19-nortestosterone derived progestagens
      [norethisterone (NE), levonorgestrel (LNG), 3-ketodesogestrel (KDG), gestodene
      (GES), Org 30659] were studied for their effect on cell growth of two human
      breast tumor T47D cell lines of different origin, i.e. from ATCC (A) and
      Sutherland (S) et al. [Sutherland et al., Cancer Res. 48 (1988) 5084-5091]. The
      effect of estradiol (E2) and progestagens alone as well as the combined effect of
      E2 (10(-10) M) and progestagens were investigated at several dose levels.
      Compared with E2-induced growth at 10(-10) M, pregnane and 19-nortestosterone
      derived progestagens at 10(-6) M alone did enhance cell growth in T47D-A cells up
      to 25 and 100% respectively, whereas in T47D-S cells they did not influence
      growth. All these progestagens at 10(-6) M did not affect E2-induced growth in
      T47D-A cells, whereas in T47D-S cells they completely reduced cell proliferation
      at doses between 10(-10) and 10(-8) M. The involvement of progestagen (PR) and
      estrogen (ER) receptors with respect to growth stimulation was studied by using
      specific antihormones. In T47D-A cells, the antiprogestagens RU 38486 and Org
      31710 could not block progestagen-induced growth. Antiestrogens, like 4
      hydroxytamoxifen and ICI 164,384, inhibited the 19-nortestosterone derivative
      induced cell growth by approx. 50%. Remarkably, both antiprogestagens alone could
      also inhibit E2-induced growth in T47D-A cells by about 50%. In T47D-S cells, E2
      induced cell growth was completely blocked by both antiprogestagens and
      antiestrogens. Both antiprogestagens in T47D-S cells were equipotent to 4
      hydroxytamoxifen and 10-fold more potent than ICI 164,384. In conclusion pregnane
      and 19-nortestosterone-derived progestagens stimulated cell growth in T47D-A
      cells at high unphysiological concentrations, whereas they did not affect cell
      growth in T47D-S cells. The 19-nortestosterone derivative induced growth in T47D
      A cells could partially be inhibited by antiestrogens. In T47D-A cells, E2
      induced cell growth was not influenced by both classes of progestagens, whereas
      in T47D-S cells all tested progestagens, antiprogestagens, and antiestrogens
      inhibited E2-induced cell growth completely. These results with T47D cells as
      well as those obtained previously with MCF-7 cells show that subclones of cell
      lines may respond differently to various types of progestagens in the presence
      and absence of estrogens.

PMID- 8541242
TI  - The cost of cognitive impairment in schizophrenia.

PMID- 8541243
TI  - Facial processing in schizophrenia and delusional misidentification: cognitive
      neuropsychiatric approaches.
AB  - The human face is of great importance as a stimulus in view of the detailed
      information it contains--information vital to understand in order to survive in
      the complex social world. There are different aspects to facial processing,
      including: affect analysis, recognition of individuality and recognition of
      familiarity, all of which have been incorporated into the cognitive model of
      Bruce and Young (1986). The cognitive neuropsychiatric approach has recently been
      employed in the study of facial processing in schizophrenia. It has become
      apparent that schizophrenic subjects are impaired in facial processing tasks at
      all levels, and this may well be related to the misinterpretation of social
      interactions commonly found in such subjects. This approach has also led to a
      greater understanding of delusional misidentification, with particular syndromes
      explained in terms of processing deficits at different levels of the cognitive
      model above. At an anatomical level, the role of the right hemisphere in facial
      perception is well-known, with there being some evidence of right hemisphere
      hypofunction in subjects with schizophrenia and also in delusional
      misidentification. The review therefore emphasizes the importance of the
      neuropsychiatric approach for further investigation of facial processing and
      understanding of symptomatology in schizophrenia and related psychoses.

PMID- 8541244
TI  - Assessing cognitive function in schizophrenics and patients with Alzheimer's
      disease.

PMID- 8541245
TI  - Cognitive impairment as a target for pharmacological treatment in schizophrenia.

PMID- 8541246
TI  - Cognitive functioning in chronically hospitalized schizophrenic patients: age
      related changes and age disorientation as a predictor of impairment.
AB  - Although schizophrenic patients manifest cognitive impairments, there is
      considerable variability across patients in the severity of this impairment. Very
      chronic patients with a poor outcome, particularly geriatric patients, manifest
      the most severe impairments, which have often been characterized as resembling
      dementia. This study examined age-related changes in cognitive functioning in a
      sample of schizophrenic patients (n = 393) ranging from 25 to 95 years of age,
      with a specific focus on identifying aspects of performance that were impaired in
      the youngest patients and preserved in the oldest patients. Age disorientation
      was examined in detail because it was previously found to predict global
      intellectual impairment in chronic patients. All 22 test items changed linearly
      over time (with age), with aspects of orientation, concentration, and delayed
      recall most impaired in young patients and naming and sentence repetition most
      preserved in the oldest patients. Age disoriented patients had more severe
      cognitive impairments at each age and the age-related changes in global
      impairment were more severe for these patients. The prevalence of age
      disorientation was consistent with previous reports and a one-year retest of the
      sample found that age disorientation was extremely stable over time within
      patients. The types of functions that are preserved in the oldest patients
      underscore previous findings of differences between geriatric schizophrenic
      patients and patients with degenerative diseases and the stability of age
      disorientation suggests that it is a trait of a subset of schizophrenic patients,
      those who appear to have the most severely declining course of illness.

PMID- 8541247
TI  - A pen-and-paper human analogue of a monkey prefrontal cortex activation task:
      spatial working memory in patients with schizophrenia.
AB  - In order to pursue the hypothesis that the dorsolateral prefrontal cortex is a
      source of cognitive deficit in schizophrenia, we developed an easily administered
      pen-and-paper human analogue of a visuospatial working memory task that in non
      human primates activates the neurons of Walker area 46 (Goldman-Rakic, 1987).
      Compared to normal controls, schizophrenic patients made significantly greater
      errors in identifying where a visuospatial stimulus had been presented to them 30
      and 60 seconds earlier, and these differences were significantly greater than in
      an immediate recall condition. These data suggest that schizophrenic patients
      have visuospatial working memory deficits that are sensitive to pen-and-paper
      versions of the tasks that activate the Walker area 46 in non-human primates. The
      availability of an easily administered test that may be associated with the
      functioning of the prefrontal cortex may enable more specific assessment of this
      brain region in humans.

PMID- 8541248
TI  - Neuropsychological and olfactory dysfunction in schizophrenia: relationship of
      frontal syndromes to syndromes of schizophrenia.
AB  - Behavioural changes and cognitive impairments in schizophrenia have been linked
      to disturbances of complex neural networks involving both frontal and subcortical
      systems. Current literature has emphasised the role of the dorso-lateral
      prefrontal cortex (DLPFC) and its connections with hippocampus in the
      pathogenesis of schizophrenia. Based on a review of the literature, this paper
      examines other possible prefrontal areas that contribute to the manifestations of
      schizophrenia. We focus on the orbito-frontal cortex (OFC) and argue that it also
      plays an important role in the behavioural manifestations, symptoms and cognitive
      impairments observed in schizophrenia. The importance of fronto-striato-thalamic
      circuits connecting these prefrontal sites with subcortical structures is
      examined and the relevance of functions specific to these circuits or their
      components are briefly discussed. The subdivision of the functions of the
      prefrontal cortex into 'prefrontal' syndromes are examined and related to both
      the behavioural and symptom-based syndromes of schizophrenia. Possible
      dissociations of function of the various prefrontal syndromes and the
      relationship of these to schizophrenia syndromes may provide clues to the
      underlying neurobiology of schizophrenia. The use of tasks deemed specific to
      DLPFC and OFC networks may be useful as probes to examine the integrity of these
      circuits. We discuss such 'circuit-specific' tasks including delayed response,
      delayed alternation and object alternation tasks derived from the animal
      literature and other tasks such as olfactory identification ability. This
      approach raises the possibility that a number of prefrontal cortical areas and
      their subcortical connections are important in accounting for the heterogeneity
      of schizophrenia.

PMID- 8541249
TI  - Anterior hippocampal volume reductions predict frontal lobe dysfunction in first
      episode schizophrenia.
AB  - This study examined relations of mesiotemporal lobe tissue volumes with
      neuropsychological (NP) functions in a sample of patients with first episode
      schizophrenia. Three contiguous compartments of the mesiotemporal lobe were
      measured on magnetic resonance images, comprising primarily amygdaloid, anterior
      hippocampal, and posterior hippocampal tissue volumes. NP measures were derived
      from a comprehensive battery. Decreased volume selectively in the anterior
      hippocampal formation was associated with lower scores on measures of executive
      and motor functions usually considered sensitive to the integrity of frontal lobe
      systems. Measures of other NP functions, and global intellectual ability, were
      not related to mesiotemporal volumes. The findings that morphologic abnormalities
      in the mesiotemporal lobe are associated with impairment of frontal lobe
      functions point to a defect in an integrated functional system that includes both
      frontal and mesiotemporal components. The findings are consistent with the
      hypothesis that neurodevelopmental defects affecting the morphology of the
      anterior hippocampal formation may be manifest later in life as impairments in
      fronto-limbic control. </p>.

PMID- 8541250
TI  - Schizophrenia, symptomatology and social inference: investigating "theory of
      mind" in people with schizophrenia.
AB  - It has been proposed that certain psychotic symptoms associated with
      schizophrenia reflect a deficit in the ability to appreciate other people's
      mental states (Frith, 1992). This notion is tested using a newly devised task
      examining the capacity to infer intentions behind indirect speech. The findings
      support the notion that some patients with schizophrenia have difficulties with
      tasks requiring 'theory of mind' skills and that this deficiency is symptom
      specific. The findings are discussed with reference to the cognitive skills which
      may be involved in the performance of tasks requiring social inferences.

PMID- 8541251
TI  - Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia.
AB  - Recent neuroimaging studies of patients with schizophrenia have suggested
      structural and functional abnormalities of mesial temporal lobe structures. We
      compared the intelligence and memory test performance of 70 patients with
      schizophrenia and 72 patients with focal, lateralized temporal lobe epilepsy (30
      left, 42 right temporal lobe) in order to examine the adequacy of a temporal lobe
      model of schizophrenic cognitive deficits. The groups did not differ in age,
      education, or Full Scale IQ. The right temporal lobe group had better overall
      memory performance than either the left temporal or schizophrenic patients.
      Unlike the schizophrenic patients, the memory impairment of the left temporal
      group was most evident with verbal materials and was amplified by delayed
      testing. Both epilepsy groups had better visual memory than the schizophrenic
      group. The clear differences in performance pattern between groups suggests that
      lateralized temporal lobe dysfunction does not by itself provide an adequate
      model of schizophrenic cognitive impairment.

PMID- 8541252
TI  - Emotional processing in schizophrenia: neurobehavioral probes in relation to
      psychopathology.
AB  - The application of neurobehavioral methods in functional neuroimaging can provide
      useful information on the neurobiology of schizophrenia. This process can be
      enhanced by using a standard set of procedures to construct 'neurobehavioral
      probes' which are suitable for functional imaging and provide reliable measures
      discriminating patients from healthy controls. While such probes are available
      for cognitive tasks, none has been applied to study emotional processing in
      schizophrenia. We examined emotional discrimination and experience probes and
      correlated performance with cognitive and clinical measures. Emotion
      discrimination tasks and mood induction procedures with happy, sad, and neutral
      facial expressions were administered to 40 patients with schizophrenia.
      Neuropsychological testing assessed intellectual, attention, abstraction
      flexibility, memory, language, spatial, and sensory-motor functions. Emotional
      performance was compared to a group of 40 normal subjects. Performance for face
      discrimination was impaired in patients. There was specific impairment in
      discrimination of happy expressions. Mood induction was effective in both groups,
      but diminished in patients, especially for happiness. Poorer performance in
      emotion discrimination correlated with severity of negative symptoms and bizarre
      behavior. Hallucinations were associated with more pronounced mood induction
      effects. Emotion discrimination was also correlated with abstraction, memory,
      language and spatial tasks, while mood induction effects showed no such
      associations. Thus, the impairment in discriminating and experiencing valence
      specific emotions in schizophrenia relates to symptomatology and
      neuropsychological functioning. The results encourage the use of the emotion
      discrimination task and the mood induction procedure as neurobehavioral probes in
      physiologic neuroimaging studies for investigating the neural substrates of
      emotion.

PMID- 8541253
TI  - Genetic risk of neuropsychological impairment in schizophrenia: a study of
      monozygotic twins discordant and concordant for the disorder.
AB  - We used a paradigm involving monozygotic (MZ) twin pairs discordant for
      schizophrenia (n = 20) and concordant for schizophrenia (n = 8), as well as
      normal MZ twin pairs (n = 7) in order to study cognitive measures of genetic risk
      in schizophrenia. A comparison between the unaffected twins from the discordant
      sample and the normal twins indicated subtle attenuations in some aspects of
      memory and executive functioning in the unaffected group and thus provided
      evidence for cognitive markers of a genetic component in schizophrenia. A
      comparison of the affected twins from the discordant pairs and the concordant
      twins yielded virtually no differences, suggesting that a distinction between
      familial and sporadic cases is not valid in this sample. Large differences
      between unaffected and affected members of discordant pairs on a wide variety of
      variables, including IQ, attention, memory, and executive function, highlighted
      the magnitude of disease-specific factors.

PMID- 8541254
TI  - Glucose metabolic correlates of continuous performance test performance in adults
      with a history of infantile autism, schizophrenics, and controls.
AB  - Twenty-five schizophrenic patients, fourteen adults with a history of infantile
      autism, and twenty normal controls performed a test of sustained attention, the
      degraded stimulus continuous performance test (CPT), during the 35 minute 18
      fluoro-2-deoxyglucose uptake period preceding positron emission tomographic (PET)
      scan acquisition. This is the first analysis comparing correlations between
      glucose metabolic rate (GMR) for selected regions and CPT performance. CPT
      performance differed in controls and schizophrenics, but autistics did not differ
      from either group. In controls and schizophrenic patients, task performance
      correlated with GMR in medial superior frontal gyrus and lateral inferior
      temporal gyrus, suggesting that activation of those regions is important in the
      normal performance of the task and that damage to those regions, which also
      showed low GMR in schizophrenics, contributes to the attentional dysfunction in
      schizophrenia. Also, schizophrenics showed negative correlations of task
      performance with anterior cingulate activity suggesting that overactivity of that
      region, which is involved in mental effort and whose GMR was low in our larger
      study of schizophrenia, impairs task performance in schizophrenics. Autistic
      patients showed negative correlations of medial frontal cortical GMR with
      attentional performance, suggesting that neuronal inefficiency in that region may
      contribute to poor performance.

PMID- 8541255
TI  - Latent inhibition in drug naive schizophrenics: relationship to duration of
      illness and dopamine D2 binding using SPET.
AB  - The dual aims of the study were (1) to examine the effect of neuroleptic
      medication on the expression of latent inhibition (LI) by studying LI in drug
      naive schizophrenic patients, and (2) to investigate the relationship between LI
      and dopamine D2 receptor binding in the basal ganglia using single photon
      emission tomography (SPET). Subjects constituted a sub-set of patients
      investigated in a major study of in vivo D2 receptor binding in schizophrenia
      (Pilowsky et al., 1993). Striatal D2 receptor binding was assessed in 15
      neuroleptic naive schizophrenic patients and 13 healthy volunteers. The
      performance of subjects on a within-subject auditory latent inhibition paradigm
      was also assessed. There was found to be no significant difference in LI between
      schizophrenic patients and normal controls, both groups showing a strong within
      subject LI effect. There was also found to be no association between LI and
      dopamine D2 receptor binding in either the left or the right basal ganglia. This
      lack of association indicates that LI is not directly related to post-synaptic D2
      receptor levels in the striatum. LI was, however, found to be correlated with
      duration of illness in the schizophrenic group. Patients with a relatively short
      duration of illness (< 12 months) tended to show reversed, or absent, LI whereas
      patients with a longer illness duration (> 12 months) showed intact LI. The
      effect on LI of duration of illness is consistent with previous findings that LI
      is disrupted specifically in acute, but not chronic, schizophrenia. Previous
      studies have assumed that this pattern of results is due to the stabilising
      effect of long-term neuroleptic medication. The present findings in a sample of
      neuroleptic naive schizophrenic patients indicate that this is unlikely to be the
      case. Rather, it appears that the reinstatement of LI in schizophrenic patients
      over time is due to a factor(s) intrinsic to the evolution of the schizophrenic
      illness.

PMID- 8541256
TI  - Brown recluse spider envenomation of the eyelid: an animal model.
AB  - The authors developed a rabbit model of the brown recluse (BR) spider
      envenomation of the human eyelid. The spider bite causes cutaneous necrosis and
      systemic toxicity in human eyelids, possibly leading to disseminated
      intravascular coagulation, hemolysis, and death. The treatment has been
      controversial. The animal model evaluated the effects of single- and combined
      agent therapy in four phases: venom dose response, time course, therapeutic
      effectiveness (steroid vs. dapsone vs. antivenom), and optimal therapy (steroid
      and dapsone; steroid and antivenom; and dapsone and antivenom combination
      groups). The combination dapsone and antivenom treatment group was the optimal
      animal regimen, although not completely effective in eliminating microscopic
      necrosis. The authors also report dramatic clinical improvement in human
      inflammatory response with dapsone therapy and recommend immediate dapsone
      therapy combined with specific BR venom, if available, in humans.

PMID- 8541257
TI  - Pseudodacryocystitis arising from anterior ethmoiditis.
AB  - The contiguous spread of inflammation from infected ethmoid sinuses to the
      surrounding tissues of the lacrimal drainage system can produce symptoms easily
      confused with acute dacryocystitis. We report the cases of two patients with
      presumed dacryocystitis whose patency of the lacrimal apparatus was established
      by probing, irrigation, and dacryocystography. Computerized tomography and
      magnetic resonance imaging demonstrated opacification of anterior ethmoid air
      cells adjacent to the region of the lacrimal sac. A greater awareness of this
      diagnostic possibility of pseudodacryocystitis arising from anterior ethmoiditis,
      together with improved noninvasive imaging techniques, will likely increase the
      observed incidence of this disease. This distinction is important since anterior
      ethmoidectomy, rather than dacryocystorhinostomy, is the treatment of choice when
      such pseudodacryocystitis proves unresponsive to antibiotic therapy. In
      misdiagnosed patients who undergo dacryocystorhinostomy, it is the coincidental
      limited anterior ethmoidectomy and not the lacrimal-nasal fistula that provides
      the cure.

PMID- 8541258
TI  - Primary and secondary orbital melanomas: a clinical and prognostic study.
AB  - The clinical, radiologic, and histologic features of 14 cases of orbital melanoma
      are reviewed. Two cases were presumed to be primary orbital melanomas because no
      primary pigmented lesion was found in the globe, conjunctiva, or skin. Five cases
      originated from a conjunctival melanoma, one case from an eyelid cutaneous
      melanoma, and the remaining six patients had extrascleral extension of a
      choroidal melanoma. Four patients at the time of first diagnosis already had
      extraorbital metastases (one patient with extrascleral extension of a choroidal
      melanoma also had a metastasis to the opposite orbit). The median time interval
      between diagnosis and metastasis was 14 months. Patients without metastatic
      disease received radical surgery (partial or total orbital exenteration, in
      addition to regional lymph node resection if indicated) or conservative treatment
      (tumor excision plus chemotherapy and interferon). Log-rank test showed an
      equally poor prognosis for both groups (median time to metastasis was,
      respectively, 19.5 and 8 months), with no statistically significant difference
      between the two groups. The authors' reconstructive techniques (dermis-fat
      grafting and transplantation of temporalis muscle) following partial- and total
      orbital exenteration are described.

PMID- 8541259
TI  - Mesenchymal chondrosarcoma with secondary orbital invasion.
AB  - Orbital involvement with mesenchymal chondrosarcoma is rare. Until recently,
      despite the young age of the affected population, exenteration was the
      recommended management. We report a patient with orbital invasion by mesenchymal
      chondrosarcoma managed surgically without exenteration. Adjuvant chemotherapy and
      radiotherapy were administered. There is no evidence of local or distant tumor
      recurrence with 30 months of postoperative follow-up. This and other recent case
      reports suggest that exenteration may not be necessary for local tumor control of
      mesenchymal chondrosarcoma in the orbit.

PMID- 8541260
TI  - Dermoid cysts: 16-year survey.
AB  - A total of 145 patients with orbital dermoid cysts examined at the Orbital
      Clinic, Institute of Ophthalmology, School of Medicine, University of Naples
      "Federico II" over a period of 16 years were reviewed. The orbital cysts were
      classified as exophytic and endophytic, according to their site of attachment in
      relation to the orbital rims. This classification can explain the different
      natural history of these lesions. The exophytic cysts growing externally are
      discovered in childhood, whereas the endophytic ones are discovered later in life
      when they produce bone damage, with or without invasion of the adjacent
      structures.

PMID- 8541261
TI  - Pediatric orbital tumors in Turkey.
AB  - A retrospective review of 376 pediatric orbital tumor cases seen at the Ankara
      University Eye Clinic between 1963 and 1993 was undertaken. The diagnosis was
      made histologically in every case. Secondary tumors accounted for 127 cases
      (33.8%), cystic lesions for 82 cases (21.8%), rhabdomyosarcomas for 23 cases
      (6.1%), vascular lesions for 21 cases (5.6%), inflammatory lesions for 21 cases
      (5.6%), lymphoma and leukemias for 18 cases (4.8%), other mesenchymal tumors for
      11 cases (2.9%), metastatic tumors for 5 cases (1.3%), traumatic foreign bodies
      for 2 cases (0.5%), and lacrimal fossa lesions for 1 case (0.3%). The most common
      benign orbital tumors were the cystic lesions. The most common primary malignant
      tumor was rhabdomyosarcoma. Overall, the most frequent orbital lesion was the
      secondary orbital invasion of retinoblastoma.

PMID- 8541262
TI  - Total integration of an ocular implant/prosthesis: preliminary in vivo study of a
      new design.
AB  - An ocular implant designed to simplify surgical implantation, minimize infection
      and extrusion, and improve motility when used as a prosthetic replacement for
      eyes removed because of damage or disease was tested in rabbit eyes. The implant
      consisted of a silicone sphere with patches of porous silicone elastomer at the
      natural insertion sites of the extraocular muscles. Nine implants also had patch
      material around the base of an integral post designed to distribute the weight of
      and transfer motility to an overlying prosthetic conformer. Six implants without
      posts had a circular porous patch on the central anterior surface to facilitate
      closure of the conjunctiva and Tenon's capsule. Biocompatibility and feasibility
      were tested in rabbit eyes for < or = 1 year. The patches promoted conjunctival
      ingrowth, leading to positional stability, and facilitated adherence of the
      extraocular muscles. Patch material around the post or on the anterior
      conjunctival surface enhanced conjunctival closure and healing. All 15 implants
      were retained with no signs of migration, conjunctival dehiscence, or extrusion.
      Motility on forced duction testing was significant in all directions. The
      materials appeared to be biocompatible, and the design with the post provided
      good motility, with the potential for improved coordinated eye movement as a
      result of the specifically localized attachment of the extraocular muscles.

PMID- 8541263
TI  - Noninfectious inflammatory response to gold weight eyelid implants.
AB  - We describe three patients with noninfectious inflammatory reactions to gold
      weight eyelid implants, a complication not previously reported. Eyelid edema and
      erythema developed gradually in each patient, and maximal inflammation that
      prompted treatment was present at 12, 3, and 5 weeks, respectively, after surgery
      in the three patients. Management involved removal of the implant in the first
      patient, oral corticosteroids followed by replacement of the implant by a
      platinum weight in the second patient, and a local corticosteroid injection with
      retention of the implant in the third. Histopathological features included a
      thick eosinophilic coagulum at the tissue-gold interface and an intense,
      predominantly lymphocytic infiltrate in the collagenous capsule that surrounded
      the implants. Gold weight eyelid implants can elicit a gradually progressive
      inflammatory response. In at least some cases, local corticosteroid injection may
      suppress the inflammation and permit retention of the implant.

PMID- 8541264
TI  - A rationale for the selection of nasal decongestants in lacrimal drainage
      surgery.
AB  - Adequate hemostasis during lacrimal drainage surgery affects the success of the
      operation. Nasal decongestants, which are sympathomimetric agents including
      sympathomimetic amines and imidazoline derivatives, help to decrease bleeding.
      Certain of the imidazoline derivatives--oxymetazoline and xylometazoline--are
      potent and long-acting agents that have many of the same adrenergic effects as
      cocaine. Their use as an alternative to cocaine provide adequate hemostasis with
      less adverse reactions than cocaine. The authors recommend premedication of the
      nasal mucosa with oxymetazoline or xylometazoline before lacrimal drainage
      surgery for obtaining maximal nasal mucosal decongestion.

PMID- 8541265
TI  - Transcanalicular removal of silastic nasolacrimal tubes.
AB  - Removal of nasolacrimal tubes is often an awkward procedure when performed
      transnasally, especially in children and apprehensive adults. We evaluated in a
      prospective fashion the transcanalicular route to retrieve nasolacrimal tubes.
      Overall, this technique was well tolerated by patients and easy to perform. Tube
      breakage during removal may be a complication.

PMID- 8541266
TI  - Problems to solve.

PMID- 8541267
TI  - Valsalva DCR bubble test.

PMID- 8541268
TI  - Aldose reductase (EC 1.1.1.21) activity and reduced-glutathione content in lenses
      of diabetic sand rats (Psammomys obesus) fed with acarbose.
AB  - The effects of acarbose on cataract development, lens aldose reductase (EC
      1.1.1.21) activity and lenticular reduced-glutathione content in diabetic sand
      rats (Psammomys obesus) were determined. Diabetic sand rats (diet-induced) were
      fed on diets with or without acarbose (0.4 g/kg) for 39 d. Daily plasma glucose,
      cataract incidence, aldose reductase and glutathione content were evaluated.
      After 19 d on acarbose, daily plasma glucose profile was significantly reduced
      compared with that of sand rats not receiving acarbose. Cataract incidence was
      markedly lower in sand rats treated with acarbose. After 20 d, cataracts had
      developed in 90% of the animals fed without acarbose, whereas none was observed
      in sand rats fed with acarbose. After 37 d acarbose treatment the incidence of
      cataracts reached only 30%. Compared with untreated animals, lens aldose
      reductase activity was significantly lower in sand rats fed with acarbose for 39
      d (7.6 (SE 0.78) v. 3.5 (SE 0.55) mumol NADPH/mg protein per min respectively, P
      < 0.001). Concomitantly, significantly higher lenticular protein and reduced
      glutathione contents (90 (SE 23) v. 240 (SE 23.5) micrograms/mg tissue
      respectively, P < 0.001 and 369 (SE 48.6) v. 645 (SE 71.1) micrograms/mg tissue
      respectively, P < 0.001) were found. These results suggest that decreasing
      hyperglycaemia, accompanied by lower aldose reductase activity obtained by
      acarbose, led to a significant preventive effect on cataract development in sand
      rats.

PMID- 8541269
TI  - Simulation of the effects of diet on the contribution of rumen protozoa to
      degradation of fibre in the rumen.
AB  - A previously described mathematical model, that stimulates the metabolic
      activities of rumen bacteria and protozoa, was used to examine the contribution
      of protozoa to neutral-detergent fibre (NDF) degradation in the rumen of cattle.
      Comparisons between predicted and experimentally observed NDF degradation showed
      general agreement. Further simulations were performed with diets containing
      variable proportions of concentrate (between 0 and 1 kg/kg diet DM) and at intake
      levels ranging between 5.3 and 21.0 kg DM/d. The simulated protozoal contribution
      to NDF degradation was 17-21% at the lowest intake level. Except for the all
      concentrate diets, raising the feed intake level reduced this contribution to 5
      13% at the highest intake level. The changes in contribution of protozoa to NDF
      degradation were related to variations in the fibrolytic bacteria: protozoa value
      and the NDF-degrading activities of protozoa predicted by the model. In
      simulations where dietary NDF levels were reduced and starch and sugar levels
      were increased independently, protozoal contribution to NDF degradation generally
      increased. These differences were reflected also in the generally increased
      protozoal contribution to NDF degradation predicted in response to a decreased
      roughage:concentrate value. The contribution of protozoa also generally declined
      in response to added N. These changes in predicted protozoal contribution to NDF
      degradation resulting from dietary variations provided possible explanations for
      the differences in rumen NDF degradation observed when animals are defaunated.

PMID- 8541270
TI  - Mechanisms of intestinal phosphate transport in small ruminants.
AB  - In order to study the localization and mechanisms of intestinal phosphate
      transport in sheep and goats, unidirectional inorganic phosphate (Pi) flux rates
      across isolated stripped epithelial tissues were measured in vitro by applying
      the Ussing-chamber technique. In the first experiment the tissues were obtained
      from animals which had been kept on an adequate dietary P supply. In the second
      experiment the animals had either been kept on an adequate Ca and P supply or
      were Ca- and/or P-depleted. Significant net Pi absorption was measured in all
      segments of the small intestine and in the proximal colon of sheep and in the
      duodenum and jejunum of goats. Since the experiments were carried out in the
      absence of any electrochemical gradient, this clearly indicates the presence of
      active mechanisms for Pi transport in the intestinal tract of small ruminants. In
      sheep jejunum, reduction of mucosal Na concentration to 1.8 mM or serosal
      application of ouabain (0.1 mM) resulted in significant decreases of net Pi
      absorption of the same order of magnitude, indicating that about 65% of active Pi
      transport in sheep jejunum is mediated by a Na-dependent active transport
      mechanism. The mechanism for the remaining Na(+)-independent active Pi transport
      has not yet been identified. Dietary P depletion caused hypophosphataemia and
      induced a significant stimulation of net Pi absorption in goat duodenum and
      jejunum. This increase was independent of dietary Ca supply and was not
      associated with increased plasma calcitriol concentrations. This suggests
      substantial differences in hormonal regulation of Pi transport in small ruminants
      in comparison with single-stomached species.

PMID- 8541271
TI  - Attitudinal dimensions of food choice and nutrient intake.
AB  - A diet low in fat and rich in fibre has been recommended to optimize general
      health and in particular cardiovascular health. Health attitudes to fat and fibre
      were studied in relation to food and nutrient intake and sociocultural and
      lifestyle factors amongst the general population of Northern Ireland. The study
      population comprised 592 adults aged 16-64 years; health attitudes to fat and
      fibre were assessed by questionnaire (based on a social psychological model,
      which adjusted for taste and convenience factors). Dietary intake was estimated
      using the weighed inventory technique. Fat-phobic and fibre-philic attitudes were
      more prevalent in women than men. Fat-phobic attitudes in women were inversely
      related to intake of fat through a reduced intake of chips, butter and sausages.
      In contrast, men's fat-phobic attitudes were not strongly correlated with fat
      intake; consumption of chips and sausages was negatively associated with fat
      phobic attitudes, but cake/biscuit, buns/pastries and milk consumption was
      positively associated with fat-phobic attitudes. Fibre-philic attitudes were
      positively associated with dietary fibre intake; intakes of potatoes, vegetables,
      wholemeal bread and breakfast cereal were positively associated with fibre-philic
      attitudes. There were clear sociocultural and lifestyle differences in relation
      to dietary attitude. These findings have implications for campaigns designed to
      effect population dietary change.

PMID- 8541272
TI  - Trans fatty acids in the Scottish diet. An assessment using a semi-quantitative
      food-frequency questionnaire.
AB  - Trans fatty acids produced during hardening of oils have been associated with
      higher cholesterol levels and increased risk of heart disease. The potential risk
      from trans fatty acids may be greater in populations with relatively low intakes
      of essential fatty acids such as the Scots, who also have a high prevalence of
      heart disease. Means and ranges of trans fatty acid intakes are reported here for
      a Scottish population. A semi-quantitative food-frequency questionnaire was used
      to survey the diet of 10,359 Scottish men and women aged 40-59 years in 1984-6 as
      part of the baseline Scottish Heart Health Study. Trans fatty acid levels were
      calculated for each food item on the questionnaire and the total subdivided into
      that which is derived naturally (primarily by bacterial fermentation in
      ruminants) and that which is produced during industrial hydrogenation (hardening)
      of vegetable and fish oils. Means and ranges of intakes of each trans fatty acid
      variable were calculated by sex, age, smoking and social class groups. Mean total
      trans fatty acid intakes for men were 7.1 (SD 3.1) g/d, 2.7 (SD 2.9)% energy and
      for women were 6.4 (SD 2.9) g/d, 3.3 (SD 3.0)% energy. Industrially hydrogenated
      trans fatty acids made up nearly 58% of the total intake for men and 61% for
      women, with about 60% coming from cakes, biscuits and sweets, and 20% coming from
      the cheaper hard margarines. The main sources of the naturally derived trans
      fatty acids were red meat (27%), milk (20%), butter (18-19%) and cheese (13-16%).
      Differences between age, smoking and social class groups were apparent. However,
      apart from the social class differences of up to 1 g/d, these were so small that
      they are unlikely to be of any biological significance unless compounded by other
      factors such as marginal essential fatty acid adequacy. The possibility of trans
      fatty acid intakes up to 48 g/d and 12% total energy (compared with the
      Department of Health (1991) recommendations of 5 g/d or 2% energy) highlights the
      need for careful monitoring of the health risks at these high levels of intake.

PMID- 8541273
TI  - Screening tests of the protein quality of grain legumes for poultry production.
AB  - Three screening tests for protein quality, modified limiting amino acid score
      (MLAAS), net weight gain (NWG) and net protein ratio (NPR), were compared. Two
      experiments using young broiler chickens were conducted in a temperature
      controlled room at 28.5 +/- 0.5 degrees with no adaptation to cages and diets, or
      at 31 +/- 0.5 degrees with 2 d adaptation to cages and diets. Nine isoenergetic
      diets containing nominally 100 g crude protein/kg supplied by legume meals and
      one isoenergetic N-free diet were randomly allocated to chicks in single cages in
      each side of a four-tier battery brooder. Each dietary treatment had eight
      replicates. The chickens had access ad lib. to diet and drinking water throughout
      a 14 d observation period. Body weight and feed were measured at the start on day
      7 and at the end on day 21. The results indicated that keeping the chickens at 31
      +/- 0.5 degrees and giving them a 2 d adaptation period decreased the variability
      of chickens' responses to each treatment. MLAAS, NWG and NPR methods could
      distinguish legume proteins of high, medium and low feed values. MLAAS correlated
      well with NWG (r 0.90; P < 0.001) and NPR (r 0.78; P < 0.01) in evaluating the
      protein quality of grain legumes used as sole sources of protein for meat
      chickens. However, MLAAS did not predict the exact order of NWG and NPR. Growth
      was limited because dietary methionine, the first limiting amino acid, provided
      only 27.6-55.2% of the recommended proportion in the protein. Although the
      results should be interpreted cautiously since a small sample size was used, it
      was concluded that the MLAAS calculation could be used as a reasonable estimate
      of the relative protein quality of most grain legumes, but that NWG and NPR were
      better methods as they detected limiting factors other than limiting amino acids
      in raw and processed legumes.

PMID- 8541274
TI  - Enrichment of an Israeli ethnic food with fibres and their effects on the
      glycaemic and insulinaemic responses in subjects with non-insulin-dependent
      diabetes mellitus.
AB  - The effects of various sources of dietary fibre on the high glycaemic index of an
      Israeli ethnic food, melawach, were investigated in subjects with non-insulin
      dependent diabetes mellitus (NIDDM). Locust-bean (Ceratonia siliqua) gum
      significantly decreased the glucose response to, and glycaemic index of, melawach
      in these diabetic subjects (P < 0.05). It also tended to decrease their
      insulinaemic response and insulinaemic index, but differences were not
      significant. Dietary fibre from lupin (Lupinus albus) and insoluble maize-cob
      fibre did not affect glucose and insulin levels in NIDDM volunteers. Subjects
      with a BMI < 30 kg/m2 exhibited similar glucose, but not insulin, responses to
      fibre. Locust-bean gum had no significant effect on glycaemic response in NIDDM
      subjects with a BMI > 30 kg/m2, whereas insulinaemic response decreased. The
      results indicate that foods containing the same nutrients in almost the same
      amounts, but differing in added dietary fibre, lead to different physiological
      responses in diabetic subjects. Furthermore, insulin response should be
      considered when fibre is incorporated into the diabetic's diet.

PMID- 8541275
TI  - Evaluation of a two-generation rat model for vitamin A deficiency and the
      interrelationship with iron metabolism.
AB  - In order to induce a range of vitamin A-deficient states in young growing rats
      and to study the effect of vitamin A deficiency on Fe status, we designed the
      following two-generation experiment. Dams were fed on diets with one of five
      vitamin A levels from 2 weeks before and throughout pregnancy and lactation. The
      pups received the same diets as their mothers both before and after weaning. The
      five dietary levels of vitamin A were 1200, 450, 150, 75 and 0 retinol
      equivalents/kg feed. Vitamin A intake did not affect reproduction outcome, nor
      were body and liver weights of the pups affected when they were 3.5 weeks old.
      Male pups with normal vitamin A status had higher plasma retinol levels than
      female pups. Vitamin A status of the offspring was affected from 3.5 weeks
      onwards. Body and liver weights were decreased in the male pups given the lowest
      dietary vitamin A levels from week 6.5 onwards but not in the female pups. Fe
      status was marginally affected. Haemoglobin levels were increased and total Fe
      binding capacity was decreased in the groups given no dietary vitamin A at week
      9.5. Splenic Fe was increased only in the male pups given the lowest levels of
      dietary vitamin A. However, as a whole, Fe status was only mildly affected and
      subject to considerable variation. We conclude that the two-generation rat model
      described here is not suitable for studying effects of vitamin A deficiency on Fe
      metabolism.

PMID- 8541276
TI  - Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel
      fungal source of gamma-linolenic acid.
AB  - The effects of oral administration of linoleic- and gamma-linolenic-acid-rich
      oils on the clinical and histopathological manifestations of experimental
      autoimmune encephalomyelitis (EAE) were investigated in Lewis rats 7 d post
      inoculation. gamma-Linolenic-acid-rich fungal (Mucor javanicus) oil at 500 mg/kg
      body weight abrogated clinical and histological signs of EAE although at doses of
      200 and 1000 mg/kg body weight it was only effective in delaying the onset of
      clinical disease. Linoleic-acid-rich safflower-seed (Carthamus tinctorius) oil at
      500, 750 and 1000 mg/kg body weight decreased the severity of clinical EAE
      disease in a dose-dependent manner. The effects in healthy animals of orally
      administered gamma-linolenic-acid-rich fungal oil (500 mg/kg body weight) and
      linoleic-acid-rich safflower-seed oil (1000 mg/kg body weight) on splenic
      lymphocyte proliferative responses to the T-cell mitogen concanavalin-A (Con A),
      membrane fatty acid composition and lymphocyte sub-sets were also studied. Both
      treatments enhanced the T-cell proliferative response to Con A. There was no
      significant effect on the proportion of splenic CD8+ or CD4+ lymphocytes.
      Compositional studies on splenic phosphoglyceride fatty acids of oil-treated
      animals suggest the above responses were associated with increases in spleen
      dihomo-gamma-linolenic and arachidonic acids.

PMID- 8541277
TI  - Do minke whales (Balaenoptera acutorostrata) digest wax esters?
AB  - Mammals are known to utilize wax esters with an efficiency of less than 50%. The
      purpose of the present study was to examine whether or not minke whales
      (Balaenoptera acutorostrata), which at times may eat considerable amounts of wax
      ester-rich krill, represent an exception to this general pattern. Samples of
      fresh undigested forestomach, as well as colon, contents were obtained from minke
      whales (n 5) that had been feeding on krill (Thysanoessa inermis) for some time.
      The samples were analysed for dry mass, energy density, lipid content and the
      major lipid classes, including wax esters. The concentrations of wax esters were
      compared with previous estimates of dry-matter disappearance of the same type of
      prey using an in vitro technique, to calculate the dry-matter digestibility of
      wax esters (DMDwax). Wax esters contributed 21% of the energy and 47% of total
      lipids in the krill diet. The energy density of gut contents decreased by 50%
      after their passage from forestomach to the end of the colon. The DMDwax was 94.1
      (SD 2.8)% (n 5). This high DMDwax and the occurrence of fatty alcohols, one of
      the products of wax-ester hydrolysis, in faeces show that minke whales are very
      efficient digesters of wax esters and absorb most of the energy-rich products of
      this process.

PMID- 8541278
TI  - Essential fatty acid status in neonates after fish-oil supplementation during
      late pregnancy.
AB  - Healthy pregnant women (n 23) were supplemented with fish-oil capsules (2.7 g n-3
      polyunsaturated fatty acids/d) from the 30th week of gestation until delivery.
      Subjects in a control group were either supplemented with olive-oil capsules (4
      g/d, n 6) or received no supplementation (n 10). Fatty acid compositions of the
      phospholipids isolated from umbilical plasma and umbilical arterial and venous
      vessel walls were determined. Fatty acid compositions of maternal venous plasma
      phospholipids were determined as well. Maternal plasma phospholipids of the fish
      oil-supplemented group contained more n-3 fatty acids and less n-6 fatty acids.
      Moreover, the amounts of the essential fatty acid deficiency markers Mead acid
      (20:3n-9) and Osbond acid (22:5n-6) were significantly lower. The extra amount of
      n-3 fatty acids consumed by the mothers resulted in higher contents of n-3 fatty
      acids, and of docosahexaenoic acid (22:6n-3) in particular, in the phospholipids
      of umbilical plasma and vessel walls. It is, indeed, possible to interfere with
      the docosahexaenoic acid status at birth: children born to mothers supplemented
      with fish oil in the last trimester of pregnancy start with a better
      docosahexaenoic acid status at birth, which may be beneficial to neonatal
      neurodevelopment.

PMID- 8541279
TI  - Impact of polyunsaturated fatty acids on human colonic bacterial metabolism: an
      in vitro and in vivo study.
AB  - Dietary polyunsaturated fatty acids (PUFA) reduce colonic proliferation and exert
      a mild laxative effect. We have studied the effect of the highly unsaturated
      eicosapentaenoic acid ethyl ester (EPA-EE) on the growth and metabolism of
      colonic bacteria in vitro, and in vivo. For the in vitro study, growth was
      assessed by viable counts. Bacteroides thetaiotaomicron was significantly
      inhibited in anaerobic media containing EPA-EE at concentrations > 7 milligrams.
      Escherichia coli was apparently resistant even at 100 milligrams. For the in vivo
      study, ten healthy volunteers ingested 18 g EPA-EE/d for 7 d. Stool frequency, 24
      h stool weight and whole-gut transit time were assessed together with breath H2
      and 14CO2 excretion following oral ingestion of 15 g lactitol labelled with 0.18
      MBq [14C]lactitol. The area under the breath-H2-time curve was significantly
      reduced by EPA-EE, from a control value of 690.3 (SE 94.2) ppm.h to 449.5 (SE
      91.7) ppm.h. Percentage dose of 14CO2 excreted, total stool weight and whole-gut
      transit time were unaltered, being respectively 24 (SE 2)%, 281 (SE 66) g and 45
      (SE 4) h with EPA-EE v. control values of 27 (SE 1)%, 300 (SE 89) g and 42 (SE 5)
      h. It is concluded that dietary supplementation with EPA-EE reduces breath H2
      excretion without apparently impairing overall colonic carbohydrate fermentation.
      The observed reduction may reflect utilization of H2 to hydrogenate the five
      double bonds of EPA-EE.

PMID- 8541280
TI  - Calorimetric detection of a sub-main transition in long-chain phosphatidylcholine
      lipid bilayers.
AB  - The existence of a sub-main transition in multilamellar bilayers composed of long
      chain saturated diacyl phosphatidylcholine (DC17PC, DC18PC, DC19PC, and DC20PC)
      is reported for the first time using high-sensitivity differential scanning
      calorimetry. The highly cooperative sub-main transition which takes place over a
      narrow temperature range positioned between the well-known pre-transition and
      main-transition is characterized by a heat capacity curve with a half-height
      width of delta T1/2 congruent to 0.15 C degrees and an enthalpy change, delta H,
      which is a few percent of the transition enthalpy for the main-transition of the
      lipid bilayer.

PMID- 8541281
TI  - Alteration by EGTA of the human red cell Ca(2+)-ATPase.
AB  - The effect of EGTA on Ca(2+)-ATPase activity was studied in fragmented membranes
      and solubilized preparations from human red cells. A dual action was found. At
      low concentrations (0.1-1 mM), EGTA increased Ca2+ affinity without affecting
      Vmax. By contrast, at high concentrations (5-10 mM), EGTA was inhibitory. Both
      effects were partially reversible.

PMID- 8541282
TI  - Analysis of the 5' end of the rat plasma membrane Ca(2+)-ATPase isoform 3 gene
      and identification of extensive trinucleotide repeat sequences in the 5'
      untranslated region.
AB  - We have characterized the 5' end of the rat gene encoding isoform 3 of the plasma
      membrane Ca(2+)-ATPase using S1 nuclease protection and DNA sequence analysis.
      The 5'-untranslated region consists of over 900 nucleotides and includes a 217
      nucleotide sequence composed of alternating tracts of TCC and ACC trinucleotides.
      Analysis of genomic sequences 5' to the transcription initiation site revealed
      potential binding sites for transcription factors that are active in muscle and
      brain.

PMID- 8541283
TI  - Differential scanning calorimetric study of the effect of vitamin D3 on the
      thermotropic phase behavior of lipids model systems.
AB  - Differential scanning calorimetry has been used to investigate the effects of
      vitamin D3 on the physical properties of model membranes including pure
      phosphatidylcholines (PC's) of chain length from 14 to 18, pure
      dipalmitoylphosphatidylethanolamine (DPPE), and various mixtures of these lipids.
      The results demonstrate that the interactions of vitamin D3 with PC's are
      dependent on acyl chain lengths. It was found that vitamin D3 reduces the
      transition temperatures of PC's and PE's, broadening the transition and reducing
      the enthalpy, eventually abolishing the transition. The interaction of vitamin D3
      with PC varies with chain length; the transition of DMPC is abolished by only 15
      mol% vitamin D3 whereas 45 mol% vitamin D3 is required to abolish the transition
      of DSPC. These variations in vitamin D3 lipid interactions are further explored
      in various mixtures. In the mixture studies it is shown that vitamin D3 affects
      the mixing properties of the lipids in the mixtures. The results suggest that the
      presence of vitamin D3 in lipids can affect the lateral phase distributions of
      lipids, and thereby have important effects on membrane function.

PMID- 8541284
TI  - Structure and properties of N-palmitoleoylgalactosylsphingosine (cerebroside).
AB  - Differential scanning calorimetry (DSC) and X-ray diffraction have been used to
      study the structure and properties of N-palmitoleoylgalactosylsphingosine (NPoGS;
      16:1 galactocerebroside). DSC of fully hydrated NPoGS shows a complex pattern of
      three endothermic transitions at 35, 39 and 53 degrees C. Using a combination of
      thermal protocols (varying heating/cooling rates, incubation at different
      temperatures, etc.), the three ordered chain (gel) phases responsible for the
      transitions have been isolated; transition I (Tm = 35 degrees C; delta H(I) = 6.3
      kcal/mol), transition II (Tm = 39 degrees C; delta HII = 8.6 kcal/mol), and
      transition III (Tm = 53 degrees C; delta HIII = 12.8 kcal/mol). The gel phases do
      not interconvert but rather form independently following cooling from the melted
      chain phase. X-ray diffraction data of the three isolated phases confirm that
      they all are bilayer structures with different bilayer periodicities (LI, 50.7 A;
      LII, 51.7 A; LIII = 49.2 A) and different chain packing modes. The LI, LII, and
      LIII bilayer phases each melt independently to the melted chain L alpha phase.
      Comparisons with other cerebrosides make it clear that alterations in chain
      length and chain unsaturation markedly affect the thermotropic behavior of
      cerebrosides and the metastable and stable phases they are able to form. As with
      phospholipids, introduction of cis-unsaturation into the N-acyl chain reduces
      both the chain melting temperature and enthalpy.

PMID- 8541285
TI  - Modulation of Na+,Ca2+ exchange current by EGTA calcium buffering in giant
      cardiac membrane patches.
AB  - Effects of calcium buffering by EGTA were examined on sodium-calcium exchange
      currents (INaCa) in inside-out giant cardiac membrane patches. Free calcium
      concentrations (Ca2+) were monitored with a calcium electrode and a fluorescent
      calcium indicator (Calcium Green-5N). With 1.8 microM cytoplasmic Ca2+, inward
      INaCa increased 2-fold at -120 mV when EGTA concentration was increased from 0.1
      mM to 10 mM (37 degrees C and 140 mM extracellular sodium). Stimulation by EGTA
      was decreased or abolished under conditions of attenuated exchanger turnover
      rate: temperature < 30 degrees C, extracellular sodium < 70 mM, and membrane
      potential > +60 mV. EGTA concentration had no effect on outward INaCa with 100 mM
      cytoplasmic Na+ and 0.8 microM cytoplasmic Ca2+, conditions under which the
      current inactivated by about 70%. EGTA (0.1-10 mM) and BAPTA (10 mM) inhibited
      the current by about 80% when the outward INaCa was stimulated by 2 mM
      cytoplasmic ATP or by phosphatidylserine. The apparent Ki for EGTA was 0.2 mM.
      The electroneutral calcium ionophore, A23187, activated outward INaCa even in
      presence of 10 mM EGTA. Our results are consistent with EGTA acting as a simple
      calcium buffer with no direct effect on the exchanger. At low concentrations of
      EGTA, inhibition of the inward INaCa is expected due to submembrane calcium
      depletion by the exchanger; enhancement of the outward INaCa at low EGTA
      concentrations is expected because submembrane calcium accumulates and activates
      INaCa via regulatory calcium binding sites.

PMID- 8541286
TI  - Magainin-induced cytotoxicity in eukaryotic cells: kinetics, dose-response and
      channel characteristics.
AB  - Magainin 1 and magainin 2 are broad-spectrum antimicrobial and antifungal
      peptides initially purified from Xenopus laevis skin glands. The mechanism of
      cytotoxicity of the naturally occurring magainin 2 and a potent all-D amino acid
      analogue, MSI-238, was examined for eukaryotic cells using flow cytometric
      analysis with propidium iodide (PI). Exposure to MSI-238 resulted in cell death
      within seconds to minutes, depending on the concentration of the peptide. Several
      cell types were examined including a mouse fibroblast cell line Balb/3T3 and a
      Rous sarcoma virus Balb/3T3-transformed cell line, SRD/3T3, primary chick embryo
      fibroblasts and cells derived from a human ovarian carcinoma, OVCA-3. The K0.5
      values determined from 5 min exposures ranged from 24 to 80 micrograms/ml for MSI
      238 and approximately 600 micrograms/ml for magainin 2. Molecular properties of
      MSI-238 induced channels were studied in excised membrane patch recordings from
      Balb/3T3 and SRD/3T3 cells. At low concentrations of 0.1 micrograms/ml,
      occasional, brief, multiple-level current fluctuations were seen suggesting
      channels with multiple, rapidly changing conductance levels. At 5 or 10
      micrograms/ml of MSI-238, the current fluctuations were larger in magnitude and
      occurred more frequently producing a general disruption of the membrane similar
      to the effects of melittin on membranes.

PMID- 8541287
TI  - Osmotic permeability in a molecular dynamics simulation of water transport
      through a single-occupancy pore.
AB  - The aim of this work is to determine plausible values for the rate constants of
      kinetic models representing water transport through narrow pores. We present here
      the results of molecular dynamics simulations of the movement of water molecules
      through a single-site hydrophilic pore. The system consists of a rectangular box
      of water molecules, some of which are positionally restrained so as to act as a
      membrane. This membrane separates two compartments where water molecules move
      freely; one of the positions in the membrane is initially vacant (the 'single
      site pore'), but can be occupied by mobile molecules. To analyze the results, we
      represented the pore by a two-state kinetic diagram in which the vacant and
      occupied states are linked by transitions corresponding to the binding and
      release of water molecules. The mean occupancy and vacancy times directly yield
      the rate constants of binding and release, which in turn yield the osmotic water
      permeability coefficient per pore pf. We also compute the apparent activation
      energies delta E* for the rate constants and for pf. The pf value was (1.56 +/-
      0.04).10(-11) cm3/s (at 307 K), which is much larger than those determined for
      CHIP28 and for gramicidin A (of about 10(-13) and 10(-14) cm3/s, respectively).
      These values were compared with those arising from a model of a symmetric single
      file pore through which one-vacancy-mediated water transport takes place. The
      model yields an expression for pf as a function of the rate constants and of the
      number of molecular positions (n) in the file. When n = 1, this expression
      becomes the one corresponding to the single-site pore studied in our current
      simulation. Using the rate constants of binding and release derived from our
      simulation, the pf values are consistent with an occupancy value of 5-6 found for
      gramicidin A, and with occupancies of 4-7 that can be estimated for the single
      file pore of a recently proposed model for CHIP28. delta E* for pf is 3.0
      kcal/mol, a value similar to that determined for CHIP28. Hence, the system
      simulated here appears plausible and can be used to mimic some physical
      properties of water transport through biological pores.

PMID- 8541288
TI  - Identification of the structural elements of amphotericin B and other polyene
      macrolide antibiotics of the hepteane group influencing the ionic selectivity of
      the permeability pathways formed in the red cell membrane.
AB  - The selectivity of the transmembrane permeability induced by polyene antibiotics
      was studied in human erythrocytes and related to the hemolytic potency of the
      drugs. The selectivity induced was differently, dependent on the antibiotic
      structure in aromatic (vacidin A, gedamycin) and nonaromatic heptaenes
      (amphotericin B, candidin). Aromatic heptaenes were more effective than
      nonaromatic in inducing permeability to K+. For both groups of antibiotics,
      permeability to K+ was not affected by substitution at the carboxyl group but
      important differences in the induction of permeability to H+, OH- and Cl- were
      found. The strongly hemolytic aromatic heptaenes vacidin A and gedamycin
      exhibited much higher protonophoric activity than the nonaromatic ones:
      amphotericin B, and candidin. The protonophoric properties of aromatic heptaenes
      were related to the presence of a free carboxyl group in the antibiotic molecule.
      Indeed the esterification or amidation of the carboxyl group of vacidin A or
      gedamycin eliminated the ability of the antibiotic to increase H+ conductance and
      consequently diminished their hemolytic activity to an important extent. Both
      groups of antibiotics differed also in the efficiency of anion permeability
      induction. Only unsubstituted aromatic heptaenes, at high concentration, induced
      Cl-/OH- exchange and conductive flux of Cl- in a concentration-dependent manner.
      Substitution at the carboxyl group of vacidin A or gedamycin eliminated this
      property. Amphotericin B as well as its carboxyl-substituted derivatives formed a
      pathway characterized by low K+ over Cl- selectivity, whatever the concentration.
      The hemolytic activity, related to K+ permeability increased by heptaenes was
      dependent on simultaneous increase of the permeability to anions, and net KCl
      influx. Carboxyl-substituted derivatives of aromatic heptaenes presenting a
      remarkably high selectivity for K+, had consequently a very poor hemolytic
      activity.

PMID- 8541289
TI  - Theoretical study of the self-association of amphotericin B.
AB  - The aim of this present work is the study of self-association of amphotericin B
      (AmB) at a molecular levels, because of its importance in the toxicity of this
      antibiotic. Molecular mechanics calculations have been performed considering
      different conformations of the polar head of AmB, the two most stable ones we
      have determined (B and C) and the one issued from the X-ray data. Our
      calculations have shown that both head-to-head and head-to-tail stable dimers
      were found within an energy range between -30 and -40 kcal/mol, the very stable
      head-to-head dimer with the polar head within C conformation having an energy of 
      46.8 kcal/mol. We have shown that both electrostatic and Van der Waals terms
      contribute to the total interaction energy but their relative weight depends on
      the conformation of the polar head and on the head-to-head and head-to-tail
      structures involved in the dimer. Thus the electrostatic contribution does no
      particularly stabilize the head-to-tail dimer. Furthermore an explicit
      calculation of the dipole moment in the ground state of AmB has disproved the
      current assertion upon the greatest stabilization of head-to-tail dimers by
      electrostatic dipole-dipole interaction. Among all the dimers we have calculated,
      we have found a group denoted G1 with a geometrical structure consistent with
      absorption data, namely a blue-shift of the dimer main absorption band with
      regard to the monomer one. In this group G1 we have found two isoenergetic (-38.8
      kcal/mol) very stable head-to-head and head-to-tail dimers. We have found that,
      as a rule, the self-association of AmB in dimers is more favourable than the
      complexation with the cholesterol and, in a less extent, with the ergosterol. It
      seems that these features could be also observed for some trimers, that we have
      roughly calculated.

PMID- 8541290
TI  - Inhibition of L-type calcium current by genistein, a tyrosine kinase inhibitor,
      in pregnant rat myometrial cells.
AB  - Possible regulation of L-type Ca2+ channels by tyrosine kinase was examined in
      freshly isolated uterine smooth muscle cells obtained from late pregnant (18-19
      day) rat, using whole-cell voltage clamp. Bath application of genistein, an
      inhibitor of tyrosine kinase, decreased L-type Ca2+ current (ICa(L)) dose
      dependently. The maximal inhibition of ICa(L) was 46% and the concentration for
      half-maximal inhibition (IC50) was 50 microM (at a holding potential of -60 mV).
      The effect of genistein was reversible. Daidzein, an inactive analog of
      genistein, had no inhibitory effect on ICa(L) at concentrations as high as 300
      microM. The steady-state inactivation curve for ICa(L) was shifted to the left by
      genistein (15 mV at 100 microM), whereas the activation curve was not affected,
      suggesting that genistein exerts.a voltage-dependent block. These results suggest
      that the L-type Ca2+ channels in myometrial cells may be modulated by endogenous
      tyrosine kinase, i.e., they are in a tonically stimulated state due to tyrosine
      kinase activity. This modulatory mechanism may play a role on the regulation of
      Ca2+ influx and uterine contraction during normal labor and preterm labor.

PMID- 8541291
TI  - NADH oxidase activity of HeLa plasma membranes inhibited by the antitumor
      sulfonylurea N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl) urea (LY181984) at an
      external site.
AB  - NADH oxidase activity from HeLa plasma membranes was inhibited by the antitumor
      sulfonylurea N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea (LY181984). With
      sealed right side-out vesicles, the drug inhibited half maximally at about 30 nM
      and the inhibition was nearly complete. A closely related but growth-inactive
      sulfonylurea, N-(4-methylphenylsulfonyl)-N'-(phenyl)urea (LY181985), did not
      inhibit the activity. With plasma membranes first solubilized with 2% Triton X
      100, activity also was inhibited by LY181984 and not by LY181985 but the maximum
      inhibition at 10 microM LY181984 was only 50%. When sealed right side-out plasma
      membrane vesicles were frozen and thawed repeatedly to evert some of the vesicles
      into an inside-out configuration, the NADH oxidase activity again was only about
      50% inhibited by 1 microM LY181984. In such preparations, the right side-out
      vesicles exhibited an electrophoretic mobility greater than that of the inside
      out vesicles. Sidedness was confiremd by measurements of ATPase latency and
      binding of immunogold-labeled concanavalin A. When the two vesicle populations
      were resolved by preparative free-flow electrophoresis, the active antitumor
      sulfonylurea LY181984 inhibited only the NADH oxidase activity of the right side
      out vesicles. These findings suggested two NADH sites or activity isoforms for
      the plasma membrane NADH oxidase. One activity, inhibited by LY181984, appeared
      to be accessible to external NADH only with sealed right side-out vesicles. The
      other, not inhibited by LY181984, was accessible to NADH only with inside-out
      vesicles or after membrane disruption by Triton X-100. The findings demonstrate
      that the NADH oxidation site inhibited as a result of binding the active
      antitumor sulfonylurea LY181984 is at the external cell surface. Plasma membrane
      vesicles from HeLa cells are able to oxidize NADH supplied to either membrane
      surface but only with inside-out vesicles is NADH oxidation sensitive to
      inhibition by the antitumor sulfonylurea.

PMID- 8541292
TI  - Effective detergent/chlorophyll ratio and detergent concentration in the aqueous
      phase during solubilization of Phormidium laminosum membranes.
AB  - Experiments of turbidity decrease induced by detergents were systematically
      performed to characterize the solubilization of Phormidium laminosum membrane
      fragments. SDS, Triton X-100 and a mixture of octyl glucoside/decyl
      maltoside/lithium dodecyl sulfate (OG/DM/LiDS, in a molar ratio of 4.19:2.54:1)
      were used. The detergent concentration in the aqueous phase (DW) and the
      effective detergent/chlorophyll ratio in mixed aggregates (Re) were determined.
      Both parameters increased during the solubilization and in an exponential way in
      the range from 10 to 90% solubilization. At detergent concentrations which caused
      the complete solubilization, Dw values were close to the described critical
      micellar concentrations (cmc), but solubilization started at concentrations well
      below the cmc. At the onset of solubilization five molecules of SDS, one of
      Triton X-100 and three of the mixture OG/DM/LiDS, per chlorophyll molecule,
      saturated the membrane fragments. The increase of Dw and Re values was
      characterized by two constants. This permits the design of a model to predict the
      detergent concentration which produces a desired solubilization of thylakoid
      membrane fragments for a given chlorophyll concentration.

PMID- 8541293
TI  - Molecular basis of glycoalkaloid induced membrane disruption.
AB  - In this study the interaction between the glycoalkaloids alpha-chaconine, alpha
      solanine and alpha-tomatine and sterols in model membranes was analysed
      systematically using techniques like membrane leakage, binding experiments,
      detergent extraction, electron microscopy, NMR and molecular modelling. The most
      important properties for sterols to interact with glycoalkaloids turned out to be
      a planer ring structure and a 3 beta-OH group, whereas for alpha-chaconine the 5
      6 double bond and the 10-methyl group were also of importance. The importance of
      sugar-sugar interactions was illustrated by the high synergistic effect between
      alpha-chaconine and alpha-solanine, the leakage enhancing effect of glycolipids,
      and the almost complete loss of activity after deleting one or more mono
      saccharides from the glycoalkaloids. The formed complexes which were resistant
      against detergent extraction existed of glycoalkaloid/sterol in a 1:1 ratio and
      formed tubular structures (alpha-chaconine) with an inner monolayer of
      phospholipids, whereas with alpha-tomatine also spherical structures were formed.
      Based on the results a molecular model for glycoalkaloid induced membrane
      disruption is presented.

PMID- 8541294
TI  - Electric field mediated loading of macromolecules in intact yeast cells is
      critically controlled at the wall level.
AB  - The mechanism of electric field mediated macromolecule transfer inside an intact
      yeast cell was investigated by observing, under a microscope, the fluorescence
      associated to cells after pulsation in a buffer containing two different
      hydrophilic fluorescent dyes. In the case of a small probe such as propidium
      iodide, a long lived permeabilized state was induced by the field as classically
      observed on wall free systems. Penetration of a 70 kDa FITC dextran was obtained
      only by using drastic conditions and only a very limited number of yeast cells
      which took up macromolecules remained viable. Most dextrans were trapped in the
      wall. A dramatic improvement in transfer of dextrans was observed when the cells
      were treated by dithiothreitol before pulsation. A cytoplasmic protein leakage
      was detected after the electric treatment suggesting that an irreversible damage
      took place in the walls of many pulsed cells. Electroloading of macromolecules in
      intact yeast cells appears to be controlled by a field induced short lived
      alteration of the envelope organization.

PMID- 8541295
TI  - Lateral domain formation in cholesterol/phospholipid monolayers as affected by
      the sterol side chain conformation.
AB  - The interaction of side-chain variable cholesterol analogues with
      dipalmitoylphosphatidylcholine (DPPC) or N-palmitoylsphingomyelin (N-PSPM) has
      been examined in monolayer membranes at the air/water interface. The sterols had
      either unbranched (n-series) or single methyl-branched (iso-series) side chains,
      with the length varying between 3 and 10 carbons (C3-C10). The efficacy of
      interaction between the sterols and the phospholipids was evaluated based on the
      ability of the sterols to form condensed sterol/phospholipid domains in the
      phospholipid monolayers. Domain formation was detected with monolayer
      fluorescence microscopy using NBD-cholesterol as the fluorescent probe. In
      general, a side chain length of at least 5 carbons was necessary for the
      unbranched sterols to form visible sterol/phospholipid domains in DPPC or N-PSPM
      mixed monolayers. With the iso-analogues, a side chain of at least 6 carbons was
      needed for sterol/phospholipid domains to form. The macroscopic domains were
      stable up to a certain surface pressure (ranging from 1 to 12 mN/m). At this
      onset phase transformation pressure, the domain line boundary dissipated, and the
      monolayer entered into an apparent one phase state (no clearly visible lateral
      domains). However, with some DPPC monolayers containing short chain sterols (n
      C3, n-C4,n-C5, and i-C5), a new condensed phase appeared to form (at 20 mol%)
      when the monolayer was compressed beyond the phase transformation pressure. These
      precipitates formed at surface pressures between 6-8.3 mN/m, were clearly
      observable up to at least 30 mN/m. When the monolayers containing these four
      sterols were allowed to expand, the condensed precipitates dissolved at the same
      pressure at which they were formed during monolayer compression. No condensed
      precipitates were observed with these sterols in corresponding N-PSPM monolayers.
      Taken together, the results of this study emphasize the importance of the length
      and conformation of the cholesterol side chain in determining the efficacy of
      sterol/phospholipid interaction in model membranes. The major difference between
      DPPC and N-PSPM monolayers at different sterol compositions was mainly the
      lateral distribution and the size of the domains as well as the onset phase
      transformation pressure intervals.

PMID- 8541296
TI  - Over-expression of a new photo-active halorhodopsin in Halobacterium salinarium.
AB  - The gene of haloopsin (hop) from halobacterial strain shark was cloned and its
      nucleotide sequence was determined. The deduced amino acid sequence of shark
      halorhodopsin (HR) showed that its homology with halobium HR was 62%. The gene
      product seems to be HR having several positively charged residues that are
      conserved in all known HRs. The gene encoding shark hop as well as that encoding
      halobium hop were successfully expressed in Halobacterium salinarium (halobium)
      by using a plasmid shuttle vector containing the bacterioopsin (bop) promoter.
      The expression level of shark HR is almost the same as that for halobium HR with
      the same shuttle vector containing the bop promoter. Under the physiological
      conditions, the anion pumping activity of the shark HR expressed in H. salinarium
      was almost the same as that for halobium HR; however, the anion selectivity and
      half-maximal anion transport were different. Furthermore, its absorption maximum
      in the absence of chloride shifted to approx. 596 nm in contrast to that for
      halobium HR. The half-lifetimes of HR520 formation for shark HR and halobium HR
      were almost the same; however, the half-lifetime of its decay was approx. 6-times
      faster for shark HR than it was for halobium HR at a high chloride concentration
      (1000 mM). Even at a low chloride concentration (50 mM), HR520 and HR640
      intermediates could be detected for shark HR, and the half-lifetime of HR640
      decay was found to be approx. 25 ms. In the presence of nitrate, the half
      lifetime of HR565 recovery for shark HR was approx. 10-times slower than that for
      halobium HR. Some of amino acid substitutions between shark HR and halobium HR
      may affect the anion selectivity and the photoreaction of HR.

PMID- 8541297
TI  - Loading of amphipathic weak acids into liposomes in response to transmembrane
      calcium acetate gradients.
AB  - We describe a novel procedure to load amphipathic weak acid molecules into
      preformed liposomes. Differences in calcium acetate concentrations across the
      liposomal membrane induce an increase of the internal pH. This pH imbalance
      serves as an efficient driving force to load and accumulate weak acids (5(6)
      carboxyfluorescein and nalidixic acid) inside the lipid vesicles. The mechanism
      of loading and the relevance of the method in drug delivery systems are
      discussed.

PMID- 8541298
TI  - Measurement of intravesicular volumes by salt entrapment.
AB  - Internal volume is a very sensitive parameter of vesicle morphology. Measurement
      of captured volumes by solute entrapment is legitimate for most types of vesicles
      (Perkin, W.R. et al. (1993) Chem. Phys. Lipids 64, 197-217). In this study
      chloride was selected as the most convenient marker ion because the ubiquity of
      Cl- in physiological buffers eliminates prelabeling with exogenous markers and
      because minute concentrations of trapped chloride are well detectable in the
      presence of large extravesicular nitrate concentrations. Perfect exchange of
      external chloride for nitrate was shown to be accomplished by gel filtration,
      dialysis, or sucrose gradient flotation-but only after significant technical
      improvements and/or elimination of experimental pitfalls. Reliability was cross
      checked by simultaneous entrapment of Cl- and K+. Diafiltration and ion exchange
      chromatography appeared inapplicable for exchange of extravesicular salt. When a
      representative variety of vesicle preparations was analyzed for internal volume
      (as well as for external surface and size) unexpected features of vesicle
      morphology were discovered. This emphasizes the genuine role of macroscopic
      vesicle characterization in complementing information from electron microscopy.

PMID- 8541299
TI  - Liposome clearance from blood: different animal species have different
      mechanisms.
AB  - The kinetics of blood clearance and the mechanisms of liposome uptake by the
      reticuloendothelial system (RES) were compared in two animal species (mice and
      rats). By employing an in situ liver perfusion technique with selected liposome
      compositions (PC/Chol, PC/Cho/PS, PC/Chol/GM1 and PC/Chol/PEG5000-PE), we
      demonstrated that liposomes with same lipid composition exhibited different blood
      circulation half-lives in different animal species. Although liver is the major
      organ responsible for the clearance of liposomes from blood in both animal
      species, the specific mechanisms differ. In mice, liposome uptake by the liver
      did not involve specific serum opsonins. In contrast, liposome uptake by the rat
      liver was strongly dependent on serum opsonins. Further, the activity of serum
      opsonins for a given liposome composition differed among animal species. Human
      serum exhibited higher opsonin activities for PC/Chol and PC/Chol/GM1 liposomes
      than bovine sera, while rat serum displayed a high opsonizing activity for GM1
      liposomes and none for liposomes composed of PC and Chol. The opsonin activity of
      human serum could be removed or decreased by treatment with EGTA/Mg2+, EDTA or
      cobra venom factor, suggesting that the activity is likely due to complement
      components. It is likely that C3 of the human complement system plays an
      important role in mediating the uptake of liposomes by the liver.

PMID- 8541300
TI  - Genetic organisation and evolution of Yersinia pseudotuberculosis 3,6
      dideoxyhexose biosynthetic genes.
AB  - 3,6-dideoxyhexose (DDH) sugars occur in some of the O antigens of Salmonella
      enterica and Yersinia pseudotuberculosis, but are otherwise rarely found in
      nature. Y. pseudotuberculosis DDH biosynthetic genes rfbS (encoding CDP-paratose
      synthetase) and rfbE (encoding CDP-tyvelose epimerase) were amplified and cloned,
      and their sequences determined. Comparisons with the equivalent genes of S.
      enterica show that the genetic arrangement of DDH genes is very similar; however,
      in Y. pseudotuberculosis there is no suggestion that paratose producing strains
      are derived from tyvelose-producing strains by inactivation of rfbE, which is the
      case in S. enterica. The previously determined DNA sequence of the rfb region of
      an abequose-producing strain was re-examined. It contains the remnants of an
      insertion sequence (IS) adjacent to a truncated and non-functional rfbE gene.
      This suggests that the IS was involved in recombination events contributing to O
      antigen antigenic diversity in Y. pseudotuberculosis.

PMID- 8541301
TI  - Pyrone hydroperoxide formation during the Maillard reaction and its implication
      in biological systems.
AB  - Hydroperoxide formation during Maillard reaction (amino-carbonyl reaction) was
      investigated using luminol-chemiluminescence-high performance liquid
      chromatography (CL-HPLC). From the equimolar reaction mixture of 1 M beta
      alanine/D-glucose in phosphate buffer (pH 8.0) at 95 degrees C, two
      hydroperoxides and H2O2 were detected as chemiluminescent products in CL-HPLC,
      and the yields were proportional to the browning development. One of these
      hydroperoxides was isolated and identified as 3-hydroxy-5-hydroperoxy-2-methyl
      5,6-dihydropyran-4-one (HMDP, pyrone hydroperoxide) by fast atom bombardment mass
      spectrometry. The HMDP formation was also confirmed in L-lysine/D-glucose and in
      bovine serum albumin/D-glucose with the physiological incubation at 37 degrees C
      for 4 days and 3 wk, respectively. Incubation at 37 degrees C of human plasma
      containing 5.5-25.0 mM of D-glucose for 60 h showed the glucose concentration
      dependent formation of HMDP (10-35 microM of H2O2 equivalence). The HMDP was
      negative to thiobarbituric acid reaction and was degraded by peroxidases such as
      horseradish peroxidase, Athromyces ramosus peroxidase, heated cytochrome c, and
      microperoxidase. The results strongly suggested the formation of such
      hydroperoxide even in biological Maillard reaction termed as glycation, and
      implied its contribution in pathogenesis and oxidative lesions associated with
      hyperglycemia.

PMID- 8541302
TI  - Carboxy-terminal cytoplasmic domain of mouse butyrophilin specifically associates
      with a 150-kDa protein of mammary epithelial cells and milk fat globule membrane.
AB  - A cDNA encoding mouse butyrophilin was obtained by reverse transcriptase-coupled
      polymerase chain reaction (RT-PCR) using poly (A)+ RNA from lactating mouse
      mammary gland as a template and screening a cDNA library with the RT-PCR
      amplified fragment as a probe. DNA sequencing and computer analysis revealed that
      it has a rather long 3'-untranslated sequence and that the carboxy-terminal
      cytoplasmic domain was well conserved between mouse and bovine butyrophilins. To
      elucidate the biological function of butyrophilin, the cytoplasmic region
      expressed as fusion protein with glutathione S-transferase (GST) was purified and
      incubated with the cell lysate of mouse mammary epithelial cell lines, COMMA-ID
      and HC11. A 150-kDa protein was shown to specifically associate with the
      cytoplasmic domain and the protein increased in amount when the cells were
      treated with basal medium supplemented with lactogenic hormones such as
      prolactin, insulin and glucocorticoid. N-terminal amino acid sequencing indicated
      that the protein is xanthine dehydrogenase/oxidase which has been cloned from
      mouse liver. Further, the cytoplasmic domain also bound xanthine
      dehydrogenase/oxidase from bovine milk fat globule membrane. These results
      suggest that butyrophilin might be physiologically associated with xanthine
      dehydrogenase/oxidase and might function in a complex form in milk fat secretion.

PMID- 8541303
TI  - Enhancement of intestinal bilirubin UDP-glucuronosyltransferase activity by
      modification of microsomal lipid composition.
AB  - Microsomal membranes from rat small intestine exhibit a higher
      cholesterol/phospholipid ratio and a lower phosphatidyl-choline/sphingomyelin
      ratio than those of the liver, which could negatively influence membrane-bound
      enzymes like bilirubin UDP-glucuronosyltransferase. To study the effect of in
      vitro modifications in the lipid composition of intestinal microsomes on
      bilirubin glucuronidating activity, two strategies were employed. On one hand,
      microsomal lipids were modified in order to mimic those of the liver tissue; on
      the other hand, cholesterol content of microsomal membranes was increased or
      decreased with respect to the normal value. Lipid changes were carried out by
      both an enzyme-mediated and a detergent-mediated procedure. Irrespective of the
      methodology employed, when a depletion in the cholesterol content was produced,
      enzyme activity increased about 40%, and when lipid composition approached that
      of the liver tissue, which not only decreased cholesterol but also modified
      phospholipid classes, enzyme activity increased about 80%. Both lipid
      modifications produced a 'fluidification' of microsomal membranes measured by
      fluorescence anisotropy of 1,6-diphenylhexatriene, being the effect of the
      approach to the liver higher than that of the decrease of cholesterol. In turn,
      the enrichment in cholesterol of microsomal membranes led to a decrease of enzyme
      activity of about 20% and to a 'rigidization' of the membranes. The present
      findings suggest that in rat intestine, bilirubin glucuronidation is strongly
      influenced by microsomal lipids. In particular, there seems to be an inverse
      association between enzyme activity and the cholesterol content of membrane.

PMID- 8541304
TI  - Purification and characterization of an AP endonuclease/DNA 3' repair diesterase
      from mouse ascites sarcoma cells.
AB  - Purification and characterization of a DNA repair enzyme having 5'
      apurinic/apyrimidinic (AP) endonuclease activity are reported. The enzyme
      extracted from mouse ascites sarcoma (SR-C3H/He) cells with 0.2 M potassium
      phosphate buffer (pH 7.5) was purified by successive chromatographies on
      phosphocellulose, DEAE-cellulose, phosphocellulose (a second time) and single
      stranded DNA cellulose, and by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The purified enzyme has an apparent molecular mass of
      30 kDa as determined by SDS-PAGE. It was shown to have nicking activity on acid
      depurinated DNA but not on intact DNA, and to have priming activities for DNA
      polymerase on acid-depurinated DNA and bleomycin-treated DNA. The results
      indicate that it is a multifunctional DNA repair enzyme having 5' AP endonuclease
      and DNA 3' repair diesterase activities. The enzyme activity is dependent upon
      the presence of a divalent cation such as Mg2+. Its amino-terminal amino acid and
      internal amino acid sequences are determined.

PMID- 8541305
TI  - Proteins lose their nitric oxide stabilizing function after advanced
      glycosylation.
AB  - In vivo generated nitric oxide, NO, circulates in plasma mainly as an S-nitroso
      adduct of serum albumin. Compared to free NO, this NO-adduct is relatively long
      lived. It exerts EDRF-like effects of vasodilation and platelet inhibition. Free
      NO is directly inactivated ('quenched') by advanced glycosylation end products
      (AGEs), glucose-derived protein moieties that form nonenzymatically and
      accumulate primarily on long-lived tissue proteins. They have been implicated in
      many of the long-term complications of diabetes mellitus. We found that the
      antiproliferative effects of thiol-stabilized NO (SNO-BSA) on Con A-stimulated
      lymphocytes from peripheral blood were even stronger than those of the NO
      generating drug SNAP. The antimitogenic activity of SNO-BSA, however, was not
      significantly enhanced by the low molecular weight NO-carrier glutathione. NO
      liberated from SNO-BSA in molar excess was almost completely quenched by AGE-BSA.
      NO-dependent activating effects such as enhanced rate of glucose uptake or
      generation of cGMP in resting peripheral mononuclear cells (PBMC) and the
      antiproliferative activity of the NO-carrier BSA on Con A-stimulated cells were
      thereby abolished. In contrast, advanced glycosylation impaired the ability of
      BSA to function as NO-carrier, as evidenced by the lack of antiproliferative
      activity of NO-AGE-BSA and its inability to activate glucose transport or cGMP
      generation.

PMID- 8541306
TI  - Isolation of prostatic kallikrein hK2, also known as hGK-1, in human seminal
      plasma.
AB  - To demonstrate the presence of kallikrein hK2 in the human prostate and seminal
      plasma, we used mouse monoclonal antibodies (MAb) against a recombinant hK2
      fusion protein. Using one of these MAb 9D5, we detected the presence of several
      major immunoreactive spots of 22 kDa and minor ones of 31 and 55 kDa in prostate
      cytosol and seminal plasma. After ion exchange and immunoaffinity chromatography
      of seminal plasma proteins, the 22-kDa immunoreactive proteins were isolated
      along with 55- and 75-kDa proteins. The NH2-terminal amino acid sequencing
      permitted identification of fragments of hK2 and protein C inhibitor,
      respectively, in the 22- ad 55-kDa bands. Furthermore, immunoblotting experiments
      in one and two-D gels with two different anti-hK2 MAbs and one polyclonal anti
      PCI antibody suggested that the major 55- and 75-kDa bands were covalent hK2-PCI
      complexes containing either the full-length hK2 chain or only its carboxyterminal
      fragment in the presence of mercaptoethanol. These results demonstrate for the
      first time the existence of kallikrein hK2 and suggest that PCI may regulate its
      activity in seminal plasma.

PMID- 8541307
TI  - Dielectric behavior of non-spherical cells in culture.
AB  - In order to study dielectric behavior of non-spherical cells growing in
      suspension culture, a dielectric theory has been developed based on the shell
      ellipsoid model that is a conducting ellipsoid covered with a thin insulating
      shell. The theory predicts three dielectric relaxations for a suspension of
      ellipsoidal cells with three different semiaxes. For prolate spheroidal cells
      with two different semiaxes that show two dielectric relaxations the effect of
      the axial ratio on the dielectric relaxations was examined in detail. The low
      frequency relaxation attributed to the component along the major axis strongly
      depends on the axial ratio, while the high-frequency relaxation due to the
      component along the minor axis is rather insensitive to the axial ratio. The
      theory is also applicable to simulation of dielectric behavior of yeast cells in
      synchronized and asynchronized culture by assuming that budding yeast cells are
      prolate spheroids.

PMID- 8541308
TI  - Oxidative stress response in yeast: glutathione peroxidase of Hansenula mrakii is
      bound to the membrane of both mitochondria and cytoplasm.
AB  - The yeast Hansenula mrakii IFO 0895 induces glutathione peroxidase (GPx) when the
      cells are exposed to the oxidative stress such as lipid hydroperoxide, superoxide
      and hydroxy radical-generating conditions. To clarify the localization of GPx in
      H. mrakii cell, distribution of the enzyme was investigated. After centrifugation
      of the yeast protoplast homogenates at 2500 x g for 10 min, 67% of total GPx
      activity was recovered from the supernatant (Sup. 1) and 33% was from the pellet
      (Pellet 1). When the Sup. 1 was fractionated by sucrose density gradient
      ultracentrifugation, GPx activity was essentially recovered from the mitochondria
      fraction. Submitochondrial localization of the enzyme showed that 95% and 2.5% of
      the enzyme was recovered from the inner and outer membrane, respectively. No GPx
      activity was detected neither in intermembrane space nor in matrix of
      mitochondria. On the other hand, at least 12% of total GPx activity was recovered
      from the purified plasma membrane which was obtained from the Pellet 1 by
      successive sucrose density gradient centrifugation. Thus, the GPx of H. mrakii is
      present in the inner and outer membrane of mitochondria as well as the plasma
      membrane.

PMID- 8541309
TI  - Regulatory subunit complex dissociated from 26S proteasome: isolation and
      characterization.
AB  - A ubiquitin (Ub)/ATP-dependent proteolytic complex (26S proteasome) purified from
      rabbit skeletal muscle was dissociated into two subcomplexes, a 20S proteasome
      and a regulatory subunit complex, by preparative non-denaturing polyacrylamide
      gel electrophoresis (PAGE). The isolated regulatory subunit complex preparation
      gave a single broad band on analytical non-denaturing PAGE, and several bands
      ranging between 33 and 110 kDa on SDS-PAGE. This complex was found to consist of
      about 20 subunits on the basis of two-dimensional PAGE, the pattern of which
      appeared identical or very similar to that of the 33-110 kDa 26S proteasome
      subunits. The apparent molecular mass of the complex was estimated to be 1100 kDa
      by Ferguson plot analysis and also by Superose 6 gel filtration. Unlike the 26S
      proteasome, neither ATPase activity nor protease activities toward Suc-Leu-Leu
      Val-Tyr-MCA, Boc-Phe-Ser-Arg-MCA, Z-Leu-Leu-Glu-beta NA, [14C]-casein, [125I]
      lysozyme and Ub-[125I]-lysozyme were significantly detectable in the regulatory
      subunit complex. This complex was found to be capable of associating with itself
      in MgATP-dependent manner. These results suggest that a regulatory subunit
      complex dissociated from the 26S proteasome comprises all the higher molecular
      mass subunits of the 26S proteasome, and has no detectable ATPase and protease
      activities, although the homo-oligomerization occurs in an ATP-dependent fashion.

PMID- 8541310
TI  - Effects of temperature shifts on the metabolism of trehalose in Neurospora crassa
      wild type and a trehalase-deficient (tre) mutant. Evidence against the
      participation of periplasmic trehalase in the catabolism of intracellular
      trehalose.
AB  - The effects of temperature shifts on the metabolism of trehalose in Neurospora
      crassa were studied in conidiospore germlings of a wild type strain, and of a
      mutant (tre), deficient in the activity of periplasmic trehalase. When the
      temperature of the medium was raised from 30 degrees C to 45 degrees C both
      strains accumulated trehalose, either in media supplemented with glucose or with
      glycerol as carbon sources. The profiles of glycolysis metabolites suggested that
      at 45 degrees C glycolysis was inhibited at the level of the phosphofructokinase
      1 reaction, while that of fructose-1,6-bisphosphatase was active, thus explaining
      how the flux of carbon from glucose or glycerol was channeled to trehalose
      synthesis at that temperature. This assumption was also supported by the changes
      in levels of fructose-2,6-bisphosphate, which dropped during the incubation at 45
      degrees C. The opposite phenomena were observed when the cultures were
      reincubated at 30 degrees C and glycolysis was strongly activated. Surprisingly,
      the intracellular pool of trehalose of the mutant decreased after reincubation at
      30 degrees C at the same rate observed for the wild type (about 25.0 nmol/min per
      mg protein) despite its low trehalase activity (about 5.0 nmol/min per mg
      protein). Labeling experiments using [U-14C]-glucose demonstrated that both the
      wild type and the mutant metabolized internally the trehalose pool, without
      detectable leakage of glucose or trehalose into the external medium. Cells
      submitted to heat shock in glycerol-supplemented medium and resuspended at 30
      degrees in the absence of an exogenous carbon source and in the presence of the
      glycolysis inhibitor 2-deoxyglucose accumulated high levels of free intracellular
      glucose, indicating that trehalose was hydrolysed internally. This suggested the
      existence of a cytosolic regulatory trehalase in Neurospora crassa, but all
      efforts to detect such activity in cell extracts have been unsuccessful so far.
      Altogether, these results argued against the participation of the periplasmic
      trehalase of N. crassa in the catabolism of intracellular trehalose. They are
      also conflictant with the enzyme/substrate decompartmentation hypothesis, earlier
      suggested as a way of explaining the mobilization of endogenous trehalose
      reserves accumulated in fungal spores (reviewed in Thevelein 1984, Microbiol.
      Rev. 48, 42-59).

PMID- 8541311
TI  - Localization of peroxisomal 3-oxoacyl-CoA thiolase in particles of varied density
      in rat liver: implications for peroxisome biogenesis.
AB  - In this paper we report on the subcellular localization of peroxisomal thiolase
      in rat liver using density-gradient centrifugation and immunoelectron microscopy.
      The results obtained show that peroxisomes display great biochemical
      heterogeneity and can not be regarded as one homogeneous population of particles.
      We conclude that rat liver contains at least three distinct populations of
      peroxisomes, which are present both in normal-fed rats as well in rats treated
      with a plasticizer, di-(2-ethylhexyl)phthalate, known to induce peroxisomes. The
      following types of peroxisomes could be discerned: (1) Low-density peroxisomal
      particles containing 69-kDa peroxisomal membrane protein (PMP),
      dihydroxyacetonephosphate acyltransferase (DHAPAT) and the precursor form of
      peroxisomal thiolase (44-kDa). (2) Intermediate-density peroxisomal particles
      containing 69-kDa peroxisomal membrane protein, dihydroxyacetonephosphate
      acyltransferase, both 41-kDa (mature) and 44-kDa (immature) peroxisomal thiolase,
      catalase and D-aminoacid oxidase. (3) High-density peroxisomes containing 69-kDa
      peroxisomal membrane protein, dihydroxyacetonephosphate acyltransferase, 41-kDa
      thiolase, catalase and D-aminoacid oxidase.

PMID- 8541312
TI  - Oxidative damage of bovine serum albumin and other enzyme proteins by iron
      chelate complexes.
AB  - Direct oxidative protein damage by iron-nitrilotriacetate (NTA), as well as
      physiological iron complexes, iron-citrate and iron-ADP was studied in the
      presence or absence of H2O2, using bovine serum albumin (BSA), glucose-6
      phosphate dehydrogenase (G-6-PD), glutathione reductase (GSSGRase) and catalase
      as the target proteins. Both Fe(III)NTA+H2O2 and Fe(II)NTA+H2O2 caused marked BSA
      fragmentation which accompanied the decrease in the intrinsic tryptophan
      fluorescence and appearance of bityrosine fluorescence. However,
      Fe(III)citrate+H2O2 showed only slight BSA fragmentation. In the absence of H2O2,
      Fe(II) NTA but not Fe(III)NTA caused similar but slight BSA fragmentation, which
      depended on the molecular oxygen. Fe(II)citrate also showed O2-dependent BSA
      fragmentation to a comparable degree, however, Fe(II)ADP showed no detectable BSA
      damage. BSA fragmentation by Fe(II)NTA+O2 and by Fe(III)NTA+H2O2 resulted in the
      appearance of the new alpha-amino groups. Electron spin resonance study using 5,5
      dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping reagent showed DMPO-OH
      spin adduct, which suggests the presence of hydroxyl radical, in Fe(III)NTA+H2O2,
      but not in Fe(II)NTA+O2 system. Fe(II)NTA inactivated G-6-PD and GSSGRase in a O2
      dependent manner, however, G-6-PD was more susceptible to the damage. This enzyme
      inactivation also accompanied the protein fragmentation and was not due to simple
      sulfhydryl oxidation. Catalase was not significantly inactivated nor fragmented
      by Fe(II)NTA+O2. These findings suggest that the interaction between proteins and
      iron-chelate complexes is important in iron catalyzed oxidative damage, and that
      the structure of the chelating agent may determine the target molecules.

PMID- 8541313
TI  - Nonenzymatic acetolactate oxidation to diacetyl by flavin, nicotinamide and
      quinone coenzymes.
AB  - Acetolactate nonenzymatically reduced flavins, quinones and nicotinamide
      coenzymes in a time-dependent manner at physiological pH and moderate
      temperature. In the presence of excess acetolactate, the reduction of FAD and
      NAD+ followed pseudo-first-order kinetics. The rate of reduction was proportional
      to the concentration of acetolactate, and the rate constants at 37 degrees C and
      pH 7.5 were 4.8 x 10(-2) M-1 s-1 and 7.4 x 10(-3) M-1 s-1 for FAD and NAD+,
      respectively. In contrast, ubiquinone reduction followed pseudo-zero-order
      kinetics in the presence of excess acetolactate. At 37 degrees C and pH 7.5, the
      rate of reduction was proportional to the acetolactate concentration, and the
      apparent rate constant was 8.3 x 10(-6) s-1. In contrast to FAD, the rate of
      reduction of ubiquinone was higher at low pH. The kinetics of ubiquinone
      reduction suggested that the rate-limiting step was acetolactate decarboxylation
      and formation of the enolate anion, whereas the rate of FAD reduction was
      governed by the second-order reaction of the enolate anion. Following the
      oxidation, acetolactate was converted to diacetyl. Reduced FAD formed by the
      reaction with acetolactate generated a low rate of O2 consumption during assays
      of the oxygenase activity of acetohydroxy acid synthase. The reaction of
      acetolactate with quinones may provide a mechanism for the nonenzymatic formation
      diacetyl in whole milk.

PMID- 8541314
TI  - Transglutaminase activity in rat liver after acute ethanol administration.
AB  - The acute effect of ethanol on hepatic transglutaminase (EC 2.3.2.13) activity
      and polyamine levels were investigated in the rat. A high dose of ethanol (5 g/kg
      body weight, given by gastric intubation) caused in homogenate and cytosolic
      fraction an inhibition of 50-70% from 3 to 24 h which thereafter was reversible.
      Such a decrease may be in part responsible for the observed enhancement in
      putrescine and spermidine contents observed at the same times. Pyrazole, an
      inhibitor of alcohol dehydrogenase, prevented the ethanol-induced reduction in
      transglutaminase activity. Disulfiram, an inhibitor of aldehyde dehydrogenase,
      allowed detection of an inhibitory effect on enzyme activity even at a low dose
      of ethanol (2 g/kg), which per se did not modify transglutaminase activity. The
      hepatic cytosolic fraction, incubated in the presence of various concentrations
      of acetaldehyde, showed a dose-dependent inhibition of transglutaminase activity.
      All of these results suggest that acetaldehyde, the first and toxic metabolite of
      ethanol, inhibits hepatic transglutaminase activity, probably by its binding to
      the active thiol site of the enzyme. The reduction in transglutaminase may lead
      to an alteration of cytoskeleton, since the enzyme is known to be involved in
      tubuline polymerization and microfilament assembly.

PMID- 8541315
TI  - Gluconeogenesis and effect of nutritional status on TCA cycle activity in the
      insect Manduca sexta.
AB  - Gluconeogenesis from isotopically substituted (3-13C)alanine (Ala) was
      demonstrated in the last larval instar of an insect, Manduca sexta, when
      maintained on low carbohydrate diets. 13C was incorporated into all carbons of
      the blood sugar trehalose (Tre), but enrichments of C1 and C6, and C2 and C5 were
      greatest. Relative to the amount of [3-13C]Ala metabolized, larvae maintained on
      a low carbohydrate diet supplemented with casein displayed the greatest
      enrichment of Tre. Very little de novo synthesis of Tre was observed in larvae
      maintained on a complete-balanced diet containing calorically equivalent amounts
      of sucrose and casein. Starvation failed to induce gluconeogenesis and 13C was
      not incorporated into Tre in starved insects. Activity of the TCA cycle
      contributed approximately 10% of the 13C incorporated into Tre in larvae on low
      carbohydrate diets, while the TCA cycle contribution in larvae on the complete
      diet approached 70%. The pattern of 13C enrichment of glucose in larvae on the
      low carbohydrate diets indicated that cytoplasmic carboxylation, possibly due to
      'malic enzyme'-like activity, contributed significantly to the synthesis of Tre.
      The pentose phosphate pathway was evidenced in insects on all diets. Glucose
      labelling ratios indicated a pentose cycling flux of 10 to 20% in insects on the
      low carbohydrate diets and 50% in larvae on the complete diet. Glutamine together
      with lesser amounts of glutamate and glutathione were also products of the
      labelled Ala. The distribution of label in these products under different dietary
      conditions demonstrated shifts in the relative contribution of pyruvate
      carboxylase and pyruvate dehydrogenase activities for providing substrate to the
      TCA cycle. In the expected fashion starved insects and insects on the low
      carbohydrate diets incorporated a greater proportion of 13C into the TCA cycle
      via carboxylation while incorporation by the two pathways was similar in insects
      on the complete diet. The significance of these findings with regard to the
      regulation of gluconeogenesis in M. sexta and comparison of the present results
      with those obtained from studies of hepatic gluconeogenesis are discussed.

PMID- 8541316
TI  - Molecular cloning of glycoprotein antigens MGP57/53 recognized by monoclonal
      antibodies raised against bovine milk fat globule membrane.
AB  - A cDNA encoding 57 kDa and 53 kDa antigens (MGP57/53) recognized by monoclonal
      antibodies raised against bovine milk fat globule membrane (MFGM) (Biochim.
      Biophys. Acta 1199 (1994) 87-95) was cloned from lactating bovine mammary gland
      by a combination of reverse transcriptase-coupled polymerase chain reaction (RT
      PCR) and 3'-rapid amplification of cDNA ends (3'-RACE). The deduced amino-acid
      sequence showed that mature MGP57/53 consists of 409 amino-acid residues and the
      calculated molecular weight and isoelectric point are 45,544 and 6.42,
      respectively. Computer analysis reveals that it has a significant similarity to
      mouse mammary epithelial cell surface protein, MFG-E8 and a human breast tumor
      associated glycoprotein antigen, BA46-1. An N-terminal cysteine-rich domain and a
      C-terminal tandemly repeated sequence were highly conserved among them, but
      bovine MGP57/53 lacks 36 amino-acid residues containing a cluster of 5 prolines
      found in mouse MFG-E8. Northern blot analysis showed that the cDNA hybridized to
      about 2.0 kb mRNA of lactating bovine mammary gland. These results strongly
      support our previous report that the two MFGM antigens originate from a single
      gene and are isoforms with different N-linked sugar chains.

PMID- 8541317
TI  - The intermediate filament structure of human hair.
AB  - X-ray diffraction studies of hard alpha-keratin have led to a proposed model for
      the lateral arrangement of molecules within the keratin fibrils of tissues such
      as hair, nail and claw. Using low-angle synchrotron radiation to examine human
      scalp hair we have obtained discrete equatorial diffraction maxima which have not
      been reported previously. These reflections can be divided into three subsets.
      The first of these reveals the information that the hair fibres consist basically
      of cylindrical fibrils arranged in a disordered lattice. The mean diameters of
      these cylinders have been determined, together with their average separation. The
      diameters of the protofibrils have been determined from the second set. The third
      set, a set of diffuse arcs, index onto a spacing which is characteristic of the
      disordered components of the matrix.

PMID- 8541318
TI  - Control by phosphatidylglycerol of expression of the flhD gene in Escherichia
      coli.
AB  - We reported elsewhere that mutation in the pgsA gene, responsible for the
      synthesis of phosphatidylglycerol, repressed the synthesis of flagellin and
      caused the loss of motility of Escherichia coli (Tomura et al., FEBS Letters 329,
      287-290, 1993). We now describe evidence for a decrease in promoter activity of
      the flhD gene, a master gene for flagellum synthesis, in the pgsA3 mutant. We
      constructed a plasmid with a promoter region of the flhD gene connected with the
      structure region of the lacZ gene. The activity of beta-galactosidase in the
      extract prepared from the pgsA3 mutant harboring the fusion plasmid was 30% of
      that in the wild type cells. This result means that phosphatidylglycerol is
      likely to be required for the initiation of transcription of the flhD gene. We
      also found that the motility-less phenotype of the mutant was partially
      suppressed by elevating incubation temperature. This suppression is caused by
      restoration of transcription of the flhD gene by high temperature. As the content
      of phosphatidylglycerol did not increase by elevating incubation temperature, we
      proposed that this suppression is caused by alternation of a physical structure
      of phospholipid bilayers in cytoplasmic membranes.

PMID- 8541319
TI  - Effects of estrogen and parathyroid hormone on osteoblastic activity via
      regulating the binding activity of insulin-like growth factor binding protein-4
      in SaOS-2 cells: implications for the pathogenesis of postmenopausal
      osteoporosis.
AB  - The cellular mechanisms involved in the accelerated bone loss occurring in
      association with estrogen deprivation as seen following the menopause have not
      been fully understood. Insulin-like growth factor-I (IGF-I) is the local
      regulator of osteoblasts and one of its binding protein, insulin-like growth
      factor binding protein-4 (IGFBP-4), binds to IGF-I and suppresses its biological
      activity. We have therefore studied the effects of 17 beta-estradiol and
      parathyroid hormone (PTH) on binding activity of IGFBP-4 and osteoblastic
      activity using SaOS-2 osteoblastic cells. DNA and collagen synthesis were
      enhanced by IGF-I or 17 beta-estradiol and suppressed by PTH in a concentration
      dependent manner. The inhibitory effect of PTH on DNA and collagen synthesis was
      abolished by the presence of IGF-I or 17 beta-estradiol. The binding activity of
      IGFBP-4 was stimulated 2-fold by 10 nM PTH, while this PTH-induced IGFBP-4
      production was completely inhibited by the addition of 17 beta-estradiol. The
      stimulated DNA and collagen synthesis by IGF-I or 17 beta-estradiol were
      inhibited by IGFBP-4 in a concentration dependent manner. The simplest
      explanation is that 17 beta-estradiol suppressed the inhibitory effect of PTH on
      osteoblastic activity by inhibiting the PTH-induced increment of IGFBP-4 binding
      activity in SaOS-2 cells.

PMID- 8541320
TI  - Isolation of a spermatozoa motility inhibiting factor from chicken seminal plasma
      with antibacterial property.
AB  - A 78-kDa spermatozoa motility inhibiting factor (SMIF) was purified from chicken
      (Gallus domesticus) seminal plasma by anion exchange (DE-53) followed by affinity
      chromatography on concanavalin A-Sepharose. The factor is thermostable and
      inhibited the spermatozoa motility in a dose dependent manner. In addition, SMIF
      inhibited the growth of gram negative bacteria, Pasteurella multocida but not
      gram positive Streptococcus equi. The factor lost its spermatozoa immobilizing
      property after treatment with trypsin, chymotrypsin or pepsin. The inhibition of
      SMIF by beta-mercaptoethanol suggest the involvement of disulfide bonds in its
      activity. Similarly, this property was lost in presence of chicken seminal plasma
      or incubating SMIF with anti-SMIF antibodies. Evidence is provided for the
      presence of a high molecular weight protein (> 100 kDa) in chicken seminal plasma
      that neutralizes the motility inhibiting property of SMIF. No significant
      decrease in spermatozoa ATP was observed in presence of SMIF suggesting that the
      loss of spermatozoa motility was due to factors other than depletion in cell's
      energy. Using anti-SMIF antibodies, a cross-reactive protein was identified in
      the blood, liver and reproductive tissues of chicken and the seminal plasma of
      cattle and buffalo. However, the cross-reactive protein failed to inhibit chicken
      spermatozoa motility. The significance of SMIF in chicken seminal plasma is
      discussed.

PMID- 8541321
TI  - Relationship between duodenal cytosolic aconitase activity and iron status in the
      mouse.
AB  - Cytosolic aconitase activity was assayed in duodenal mucosa from mice subjected
      to a variety of manipulations known to modulate duodenal iron status and duodenal
      iron absorption. No changes in cytosolic aconitase activity were observed 1 h
      after oral FeSO4 dosing or intramuscular desferrioxamine treatment. Three days of
      hypoxic exposure and two weeks treatment with intramuscular iron dextran also had
      no effect on cytosolic aconitase. Three weeks growth on an iron deficient diet
      significantly reduced cytosolic aconitase activity. In no situation was there any
      evidence for significant amounts of inactive aconitase which could be activated
      in vitro with FeSO4/cysteine. These data suggest that duodenal cytosolic
      aconitase is not sensitive to acute changes in mucosal iron levels and is
      generally much less sensitive to body iron status than is duodenal iron
      absorption. There is evidence that chronic iron depletion reduces cytosolic
      aconitase to a relatively small degree but generally activity is maintained,
      consistent with an important metabolic role for the enzyme.

PMID- 8541322
TI  - Ethanol consumption reduces the proteolytic capacity and protease activities of
      hepatic lysosomes.
AB  - Chronic ethanol consumption causes decreased hepatic protein degradation,
      resulting in protein accumulation within hepatocytes. In this investigation, we
      sought to determine whether chronic ethanol feeding alters the degradative
      capacity and protease activities of isolated hepatic lysosomes. Male Sprague
      Dawley-derived rats were fed a liquid diet containing either ethanol (36% of
      calories) or isocaloric maltose-dextrin for 1-5 wk. Hepatic lysosomes were
      isolated by differential centrifugation and purified through Percoll gradients.
      Lysosomes obtained from livers of ethanol-fed rats degraded both endogenous
      protein substrates and the exogenously added radioactive substrate, 125I-RNase A,
      26-42% more slowly than lysosomes from pair fed controls. The ethanol-elicited
      reduction in proteolytic capacity appeared to result in part, from a deficiency
      of the lysosomal cathepsins B, L, and H. Compared with controls, the specific
      activities of these enzymes were 31-45% lower in lysosomes from ethanol-fed rats.
      Immunoblot analyses also revealed that the intralysosomal as well as the
      intracellular content of cathepsin B was significantly lower in ethanol-fed rats.
      In contrast, ethanol consumption did not affect the cellular quantity of
      cathepsin L but lowered its amount in isolated lysosomes. Our findings suggest
      that chronic ethanol consumption causes a deficiency in lysosomal cathepsins by
      altering their biosynthesis and/or their trafficking into lysosomes.

PMID- 8541323
TI  - Structure of genes for sperm-specific nuclear basic protein (SP4) in Xenopus
      laevis.
AB  - Nuclear basic proteins in sperm of Xenopus laevis consist of 6 sperm-specific
      proteins (SPs1-6) in addition to somatic core histones. Using a cDNA for SP4 as a
      probe, we cloned genomic DNA containing SP4 genes from a genomic library
      constructed from recombinant lambda bacteriophage containing 12.0 kbp-EcoRI
      digests of J-strain X. laevis liver DNA. Construction of restriction maps based
      on Southern blot analysis revealed the existence of a total of five SP4 genes
      which are arranged in a tandemly repeated array forming a cluster of simple
      multigenes per haploid genome, over a range of 18 kbp. Among these genes, the one
      located at the most upstream position differed from others in possessing a single
      base substitution which gave rise to a replacement of one out of 78 amino acid
      residues. The DNA containing the second to the fourth SP4 genes, arranged at
      about 3 kbp intervals each, was totally sequenced for 10,165 bp. Each gene was
      found to contain one intron, typical TATA and CCAAT boxes in the 5'-flanking
      region, and a polyadenylation signal in the 3'-flanking region. Comparative
      sequence analyses revealed three regions of extensive homology within the
      upstream non-coding region among three genes, suggesting a possible relevance to
      their expression at a particular phase of spermatogenesis and/or in testis.

PMID- 8541324
TI  - Evidence that alpha-crystallin prevents non-specific protein aggregation in the
      intact eye lens.
AB  - The ocular lens is a transparent organ comprised of a highly concentrated and
      highly ordered matrix of structural proteins, called crystallins, which are
      probably the longest lived proteins of the body. Lens transparency is dependent
      upon maintenance of the short range order of the crystallin matrix. This
      transparency must be maintained for decades in the absence of normal protein
      synthesis or repair capacity. We present evidence here that alpha-crystallin, one
      of the major lens proteins, plays a central role in vivo in stabilizing the other
      crystallins and preventing uncontrolled aggregation of these progressively
      modified and aging molecules. alpha-Crystallin has previously been shown to
      suppress non-specific aggregation of denaturing proteins in simple binary systems
      through a chaperone-like activity. Our studies using soluble homogenates of
      monkey lenses demonstrate a strong resistance to heat induced non-specific
      aggregation when the complete complement of crystallins is present; in contrast,
      if alpha-crystallin is selectively removed prior to heating, the remaining
      crystallins undergo extensive non-specific aggregation as indicated by light
      scattering. When alpha-crystallin is present it complexes with denaturing
      proteins forming a soluble heavy molecular weight (HMW) fraction but no
      insolubilization is observed, while when alpha-crystallin is absent there is
      heavy insolubilization and no HMW formed. When intact monkey lenses were heated
      it could be demonstrated that soluble HMW was generated. Similar HMW protein
      appears in vivo in the human lens as a function of age. These findings suggest
      that the soluble HMW protein present in the human lens is the product of the
      chaperone-like function of alpha-crystallin and that under physiological
      conditions alpha-crystallin inhibits the uncontrolled aggregation of damaged
      proteins, thereby preventing the formation of light scattering centers and
      opacification of the lens.

PMID- 8541325
TI  - Cloning and expression of human cDNA encoding phosphatidylinositol transfer
      protein beta.
AB  - cDNA encoding the beta isoform of human phosphatidylinositol transfer protein was
      cloned from a human brain cDNA library. The deduced sequence of the protein
      comprised 271 amino acids with a calculated molecular mass of 31,539 Da, and
      showed 98.1% identity to that of the beta isoform of rat phosphatidylinositol
      transfer protein. The cDNA hybridized to a 3.4-kb mRNA, which was widely
      expressed in various human tissues including brain.

PMID- 8541326
TI  - Thrombocytes are the predominant source of endogenous sulfidopeptide leukotrienes
      in the American bullfrog (Rana catesbeiana).
AB  - Nucleated bullfrog erythrocytes have 5-lipoxygenase (LO) and are the first non
      mammalian cell to exhibit endogenous sulfidopeptide leukotriene (LT) synthesis.
      Non-nucleated mammalian platelets lack 5-LO, but contribute significantly to LTC4
      production by transcellular synthesis. However, nucleated bullfrog thrombocytes
      have not been examined for 5-LO activity. Endogenous leukotriene synthesis by
      bullfrog thrombocytes and mixed leukocytes was analyzed by reverse-phase high
      performance liquid chromatography (RP-HPLC). Calcium ionophore activated (A23187)
      leukocytes demonstrated 5-LO, 12-LO, and 15-LO activity. Spectral analysis
      demonstrated synthesis of LTB4, LTB4 isomers, 15(S)-monohydroxyicosatetraenoic
      acid (HETE), 5(S),12(S)-diHETE, 5(S),15(S)-di-HETE, lipoxin A4 (LXA4) and LXB4.
      Thrombocytes synthesized large quantities of sulfidopeptide leukotrienes but no
      lipoxins. Sulfidopeptide leukotriene and LTB4 radioimmunoassay analysis and the
      radiological RP-HPLC profile of [3H]AA metabolism further confirmed synthesis.
      Incubations with [3H]LTC4 demonstrated slow and incomplete conversion to
      [3H]LTD4. Thrombocyte leukotriene profile changed over time revealing a
      significant shift from the LTC4 synthase to LTA4 hydrolase pathway, corresponding
      with release of large amounts of LTA4. Thrombocytes potentially play a pivotal
      role in inflammatory and cardiovascular responses. 5-LO activity in amphibian
      homologs to mammalian platelets and erythrocytes compared with the lack of
      activity in the mammalian counterparts may correspond to the loss of the nucleus
      in the evolution of these cells.

PMID- 8541327
TI  - Acetylated low density lipoprotein inhibits the incorporation of arachidonic acid
      in phospholipids with a concomitant increase of cholesterol arachidonate in rat
      peritoneal macrophages.
AB  - The aim of our work was to evaluate the influence of native low density
      lipoproteins (LDL) and LDL chemically modified by acetylation (acLDL) on
      incorporation and release of arachidonic acid (AA) in rat peritoneal macrophages.
      Compared to a control group without treatment, 100 micrograms/ml of acLDL for 15
      h considerably increased the incorporation of [3H]AA in cholesterol-ester (CE) of
      rat peritoneal macrophages and induced a decrease of 3H-labeled membrane
      phospholipids (PL). No effect was shown with LDL treatment. In the presence of
      acLDL, LS3251 (100 nM), an acyl-coenzyme A:cholesterol acyltransferase (ACAT)
      inhibitor, inhibited the [3H]AA incorporation into CE in macrophages. [3H]AA
      prelabeled macrophages cultured for 15 h with acLDL (compared to macrophages
      untreated or treated with LDL) showed an increase of labeled CE and a decrease of
      labeled PL and of cyclooxygenase and lipoxygenase eicosanoid production. After
      zymosan stimulation of macrophages prelabeled with [3H]AA and treated with or
      without LDL or acLDL, AA release and eicosanoid production increased in all
      groups of macrophages. The inhibition of eicosanoid production in foam cells does
      not seem to be linked to an inhibition of phospholipase but rather paralleled to
      an increase of the cholesterol [3H]arachidonate. A significant portion of
      cellular arachidonate released from phospholipids, in particular from
      phosphatidylcholine, could serve as a substrate to ACAT in this foam cell.

PMID- 8541328
TI  - Structural elucidation of two novel amphoteric glycosphingolipids from the
      earthworm, Pheretima hilgendorfi.
AB  - The novel amphoteric glycosphingolipids containing a choline phosphate were
      purified from whole tissues of the earthworm, Pheretima hilgendorfi. Their
      chemical structures were completely characterized as cholinephosphoryl-->6(Man
      alpha 1-4)Gal beta 1-6Gal beta 1-1Cer
      (cholinephosphorylmannosylneogalabiaosylceramide, named PGL3a) and
      cholinephosphoryl-->6Gal beta 1-6Gal beta 1-6Gal beta 1-1Cer
      (cholinephosphorylneogalatriaosylceramide, named PGL3b) by compositional sugar,
      fatty acid and sphingoid analyses, hydrogen fluoride degradation, partial acid
      hydrolysis, methylation analysis, exoglycosidase degradation, proton magnetic
      resonance spectroscopy and fast atom bombardment mass spectrometry. The ceramide
      moieties of these lipids consisted of 22:0, 23:0 and 24:0 acids as major fatty
      acids, and branched octadeca- and nonadeca-4-sphingenines and octadeca-4
      sphingenine as main sphingoids. Since the oligosaccharides and the ceramide
      moieties of PGL3a and PGL3b were identical with those of neutral
      glycosphingolipids found in this organism, the biosynthesis of the amphoteric
      glycolipids may occur by the addition of a choline phosphate residue to the
      corresponding neutral glycolipids, Man alpha 1-4Gal beta 1-6Gal beta 1-1Cer or
      Gal beta 1-6Gal beta 1-6Gal beta 1-1Cer.

PMID- 8541329
TI  - Involvement of a cellular surface factor(s) in lipid-free apolipoprotein-mediated
      cellular cholesterol efflux.
AB  - Involvement of cellular surface factors in cellular lipid efflux mediated by
      lipid-free apolipoprotein has been investigated. Lipid-free human apolipoprotein
      (apo) A-I generated net efflux of cholesterol and phospholipid from mouse
      peritoneal macrophages and rat aorta smooth muscle cells. Ratio of cholesterol to
      phospholipid was much lower in the lipid released by this mechanism from the
      smooth muscle cells than that from the macrophages, in agreement with our
      previous observation (Li, Q., Komaba, A. and Yokoyama, S. (1993) Biochemistry 32,
      4597-4603). On the other hand, free apoA-I did not cause any lipid efflux from
      human erythrocytes. In contrast, apparent efflux of cellular cholesterol to HDL
      was similarly observed from all of these three cellular membranes. Trypsin
      treatment of the cultured macrophages completely inhibited apoA-I-mediated efflux
      of cholesterol and phospholipid. Smooth muscle cells also showed complete
      inhibition of the apoA-I-mediated cellular lipid efflux by trypsin treatment
      except that it required longer incubation with the enzyme. The same cellular
      treatment with trypsin even by prolonged incubation had only a limited effect on
      apparent cellular cholesterol efflux to HDL and apolipoprotein-free lipid
      microemulsions. Thus, free apolipoprotein-mediated cellular lipid efflux seems to
      depend on a trypsin-susceptible cellular surface factor(s) that erythrocytes may
      lack, being distinct from physicochemical cholesterol exchange reaction between
      cell and lipoprotein.

PMID- 8541330
TI  - Altered regulation of surfactant phospholipid and protein A during acute
      pulmonary inflammation.
AB  - Biochemical changes in the pulmonary surfactant system caused by exposure to
      toxicants are often accompanied by an influx of inflammatory cells into the
      lungs. We have investigated the possibility that the inflammatory and surfactant
      biochemical effects might be connected. Co-treatment with dexamethasone, a
      synthetic anti-inflammatory glucocorticoid, mitigated the increases in free cells
      and total intracellular surfactant phospholipid normally seen in animals given
      silica alone, suggesting a relationship between the free cell population of the
      alveoli and the surfactant system during alveolitis. Furthermore, we have
      investigated whether induction of the surfactant system is a universal response
      to alveolar inflammation. Inflammation was induced in the lungs by intratracheal
      injections of titanium dioxide, silica, bleomycin or lipopolysaccharide (LPS)
      suspended in isotonic saline. Inflammatory cell and surfactant responses were
      measured at 3 days and 14 days following injection. There was a distinct alveolar
      inflammatory cell profile following administration of each agent, at each time
      point, indicating a dynamic inflammatory cell population during the course of the
      study. Furthermore, surfactant phospholipid and protein A (SP-A) pools exhibited
      unique responses to the inflammatory agents. Only silica-treated lungs maintained
      elevated levels of surfactant phospholipids and SP-A throughout the course of the
      experiment. We conclude that both the surfactant components and the inflammatory
      cell population of the alveoli undergo dynamic changes following treatment with
      these inflammatory agents and that activation of the surfactant system is not a
      universal response to alveolar inflammation, since surfactant components were not
      always elevated during times of increased alveolar cellularity. The unique
      inflammatory cell infiltrate elicited by silica is of particular interest in that
      surfactant components were elevated throughout the course of the experiment in
      this group. Indeed, we have shown that the size of the intracellular pool of
      surfactant is directly proportional to the number of polymorphonuclear leukocytes
      but not alveolar macrophages or lymphocytes in the alveoli following silica
      treatment. Finally, our data suggest that the phospholipid and SP-A components of
      surfactant respond differentially to the pulmonary toxicants in this study.

PMID- 8541331
TI  - Analysis of the ligand binding properties of recombinant bovine liver-type fatty
      acid binding protein.
AB  - The coding part of the cDNA for bovine liver-type fatty acid binding protein (L
      FABP) has been amplified by RT-PCR, cloned and used for the construction of an
      Escherichia coli (E. coli) expression system. The recombinant protein made up to
      25% of the soluble E. coli proteins and could be isolated by a simple two step
      protocol combining ion exchange chromatography and gel filtration. Dissociation
      constants for binding of oleic acid, arachidonic acid, oleoyl-CoA,
      lysophosphatidic acid and the peroxisomal proliferator bezafibrate to L-FABP have
      been determined by titration calorimetry. All ligands were bound in a 2:1
      stoichiometry, the dissociation constants for the first ligand bound were all in
      the micro molar range. Oleic acid was bound with the highest affinity and a Kd of
      0.26 microM. Furthermore, binding of cholesterol to L-FABP was investigated with
      the Lipidex assay, a liposome binding assay and a fluorescence displacement
      assay. In none of the assays binding of cholesterol to L-FABP was observed.

PMID- 8541332
TI  - Effect of FR145237, a novel ACAT inhibitor, on atherogenesis in cholesterol-fed
      and WHHL rabbits. Evidence for a direct effect on the arterial wall.
AB  - The hypocholesterolemic and antiatherosclerotic activities of FR145237, a novel
      acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, were evaluated in
      cholesterol-fed and Watanabe heritable hyperlipidemic (WHHL) rabbits. In the
      first experiment, rabbits were fed a high cholesterol (1% cholesterol) diet for 2
      weeks and further fed a high cholesterol diet containing FR145237 for 8 weeks.
      FR145237 (0.1, 0.32 and 1.0 mg/kg) dose-dependently lowered the plasma total
      cholestrol levels by 80%, 96% and 97%, respectively. and reduced aortic
      atherosclerosis by 44%, 90% and 90%, respectively. To clarify a direct effect of
      FR145237 at the aortic wall, a second experiment was performed. Rabbits were fed
      a high-cholesterol diet for 8 weeks to establish aortic atherosclerosis and then
      fed a normal diet with or without FR145237 for 8 weeks. Cholesterol content in
      the aorta and the liver was significantly reduced in the FR145237 group (10
      mg/kg) by 50% and 43%, respectively, though plasma total cholesterol level did
      not differ from that in the control group. In the WHHL rabbits, FR145237 (10
      mg/kg) did not affect plasma cholesterol level but significantly reduced the
      atherosclerotic lesion in the coronary arteries by 61%. These results suggest
      that FR145237 potently lowers the plasma cholesterol level in
      hypercholesterolemia induced by dietary cholesterol but not that by LDL receptor
      deficiency, and that FR145237 has a direct antiatherosclerotic activity on the
      arterial wall independent of its hypocholesterolemic activity.

PMID- 8541333
TI  - Characteristics of ten charge-differing subfractions isolated from human native
      low-density lipoproteins (LDL). No evidence of peroxidative modifications.
AB  - Native plasma low-density lipoproteins (LDL) were fractionated into ten
      subfractions with increasingly negative charges (LDL-1, the least
      electronegative, to LDL-10) using an anion-exchange column coupled to a fast
      protein-liquid chromatography system. Prior to fractionation, contaminating Lp(a)
      and apo A-I-containing lipoproteins were removed from LDL preparations by
      immunoaffinity chromatography. No significant difference in thiobarbituric acid
      reactive substances, vitamin E or free aminogroup was found among subfractions,
      and no peptide with a higher molecular weight than apo B was observed on SDS
      PAGE. We observed a gradual increase in cholesterol esters and a concomitant
      decrease in triglycerides from LDL-1 to LDL-7, and a reverse tendency from LDL-8
      to LDL-10 (P < 0.01). Free cholesterol increased linearly from LDL-1 to LDL-10 (P
      < 0.01). LDL-1 to -3 had a homogeneous density profile, while other more
      electronegative subfractions showed a bimodal distribution with a second, minor
      peak of slightly higher density. A gradual increase in apolipoprotein C-III
      content related to LDL electronegativity was observed (P < 0.001). Apolipoprotein
      E content was also increased in the last two subfractions (P < 0.01). LDL
      subfractions displayed a similar binding fate on human fibroblasts, with the
      exception of the most electronegative subfractions [LDL-(9 + 10)], which bound
      more actively to apo B/E receptors (P < 0.05). This study shows that charge
      heterogeneity of native LDL is not related to lipid peroxidation or
      derivatization of free aminogroups of apolipoprotein B. In contrast, the
      enrichment of LDL in apolipoproteins other than apo B may explain, in part, the
      difference in their particle charge.

PMID- 8541334
TI  - Vitamin A contained in the lipid droplets of rat liver stellate cells is
      substrate for acid retinyl ester hydrolase.
AB  - Vitamin A is stored in the lipid droplets of liver stellate cells (LSCs), as
      retinyl esters whose hydrolysis is necessary for the secretion of retinol into
      the blood. Here, we isolated these retinyl esters under their physiological form,
      i.e., in LSC lipid droplets, which had retained their morphological and
      biochemical characteristics. These retinyl esters are substrate for an hydrolytic
      enzyme, whose optimum pH is 4.1, and which is kinetically similar to the acidic
      retinyl ester hydrolase (aREH) we had previously described (Mercier et al.,
      Biochim. Biophys. Acta (1994) 1212, 176-182). The cellular and subcellular
      localizations of aREH activity in rat liver suggest that this enzyme could be
      involved in the hydrolysis of the esterified vitamin A stores.

PMID- 8541335
TI  - Age-related changes in apolipoprotein A-I expression.
AB  - To determine the age-related changes in apolipoprotein A-I (ApoA1) expression,
      male Fischer 344 rats at 4 (young), 12 (intermediate age), and 24-26 (aged)
      months of age were studied. Immunoblot analysis of plasma proteins indicated that
      26-month-old rats (1.79 +/- 0.16 mg/ml) and 12-month-old rats (2.23 +/- 0.11
      mg/ml) have significantly higher plasma ApoA1 concentrations compared to 4-month
      old rats (1.14 +/- 0.15 mg/ml) P < 0.001. Hepatic ApoA1 mRNA was approx. 2-fold
      higher in aged rats compared to 12-month-old and 4-month-old rats. This increase
      in hepatic ApoA1 mRNA in aged rats was also reflected in the increased
      translation of ApoA1 mRNA in vitro. Reduced mRNA turnover may account for the
      increased hepatic ApoA1 mRNA content in 26-month-old rats, since the rate of
      ApoA1 gene transcription as measured with nuclear run off assays was
      significantly reduced with age. The ApoA1 synthesis in vivo, as measured by
      [14C]leucine incorporation at 30 min, was reduced in aged rats compared to young
      rats (170.5 +/- 10.2 vs. 253.9 +/- 7.7 cpm per liver) P < 0.001 probably as a
      result of changes related to cellular metabolism rather than an alteration
      inherent to the ApoA1 mRNA translatability. The age-related increase in plasma
      ApoA1 protein is probably secondary to reduced metabolic clearance rate of ApoA1
      protein or is the result of increased intestinal synthesis of ApoA1.

PMID- 8541336
TI  - The enhancement of phosphatidylcholine biosynthesis by angiotensin II in H9c2
      cells.
AB  - The effect of angiotensin II on the biosynthesis of phosphatidylcholine in rat
      heart myoblastic (H9c2) cells was investigated. Cells were incubated with [methyl
      3H]choline, and the labelling of phosphatidylcholine at different time intervals
      was examined. When cells were pretreated with angiotensin II, a significant
      increase in the labelling of phosphatidylcholine was observed. Analysis of the
      labelled phosphatidylcholine precursors indicated that the conversion of
      phosphocholine to CDP-choline was enhanced by angiotensin II treatment.
      Determination of enzyme activities in the CDP-choline pathway revealed that the
      activities of choline kinase or CDP-choline: diacylglycerol
      cholinephosphotransferase were not changed, but the activities of
      CTP:phosphocholine cytidylyltransferase were stimulated in both the particulate
      and soluble fractions. The stimulation of the cytidylyltransferase by angiotensin
      II was not abolished by okadaic acid, indicating that the activation of the
      enzyme was not mediated via the okadaic-sensitive dephosphorylation mechanism.
      Alternatively, the stimulation of the cytidylyltransferase activity was
      completely abolished by protein kinase C inhibitors. Immunoblotting studies
      revealed that levels of the cytidylyltransferase in the soluble and particulate
      fractions were not affected by angiotensin II treatment. We conclude that the
      increase in phosphatidylcholine biosynthesis by angiotensin II was a direct
      result of the enhancement of the cytidylyltransferase activity. The enhancement
      of enzyme activity was not mediated via enzyme translocation, but by a mechanism
      which was intimately associated with the protein kinase C cascade.

PMID- 8541337
TI  - Occurrence and biological effects of cholesteryl sulfate on blood platelets.
AB  - Although the exact function of cholesteryl sulfate (CS) is unknown, it is present
      in low concentration in lipoproteins, in red blood cells and spermatozoa. In the
      present study, we investigated whether CS is present in blood platelets and its
      possible biological involvement in platelet function. Extensively washed
      platelets were prepared from rat and human blood. After lipid extraction and thin
      layer chromatography (TLC) on silica gel, a compound with the same mobility as
      authentic CS was isolated and identified by two different methods: (1) without
      hydrolysis, negative ion fast atom bombardment combined with tandem mass
      spectrometry (MS/MS); (2) after acidic hydrolysis, identification of cholesterol
      (Chol) by TLC and gas chromatography-MS. CS concentrations measured using beta
      sitosteryl sulfate as internal standard in normal rat or human platelets were in
      the range of 164-512 pmol/10(9) platelets. This represented less than 1% of cell
      Chol. Biological effects of CS on platelet function were studied in vitro. CS
      incubated with rat platelets either as methanol solution or as albumin-bound
      complex potentiated the ADP- or thrombin-induced aggregation and serotonin
      secretion. The results of platelet sterol analysis indicated that CS was
      incorporated into platelet membrane and did not significantly change the platelet
      cholesterol composition. The potentiating effect of CS on platelet-induced
      aggregation and secretion was not obtained with cholesterol, cholesteryl acetate
      or estrone. In contrast, an inhibitory effect of estrone sulfate was observed.
      These results indicate that both the sulfate group and the cholesterol moiety are
      involved in the pro-aggregant property of CS. In addition, platelet mediators
      seem to be implicated in the mechanism since the thrombin-induced production of
      thromboxane B2, the stable end-product of arachidonic acid metabolism, was also
      enhanced in the presence of CS. These results suggest a new role for CS which may
      be involved in the modulation of platelet function.

PMID- 8541338
TI  - Digestion and lymphatic transport of eicosapentaenoic and docosahexaenoic acids
      given in the form of triacylglycerol, free acid and ethyl ester in rats.
AB  - Lymphatic transport of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids
      given as trieicosapentaenoyl glycerol (TriEPA) and tridocosahexaenoyl glycerol
      (TriDHA) was compared with that of ethyl ester and free acid in rats cannulated
      with thoracic duct. Trioleoylglycerol (TO) served as a control. EPA and DHA,
      compared with oleic acid, were slowly transported in lymph irrespective of fat
      types administered. Total 24-h recovery of DHA in all fat types and ethyl EPA was
      significantly lower compared to that of oleic acid. Lymphatic recovery of EPA and
      DHA in rats given TriEPA and TriDHA was significantly higher at the first 3 h
      after the administration compared to those given as free acid or ethyl ester. The
      recovery in rats given free acid at a later stage (9-24 h) was higher than that
      of the other fat types. As a result, the 24-h recovery was comparable between
      triacylglycerol (TAG) and free acid, while it was significantly lower in ethyl
      ester. Although TriEPA and TriDHA were slowly hydrolyzed by pancreatic lipase in
      vitro compared with TO and TAGs rich in EPA or DHA at the second position, the
      hydrolysis rate at 60 min incubation was comparable among the TAGs examined. The
      hydrolysis rate of ethyl esters was extremely low even in 6 h incubation with
      lipase. These observations show that presence of EPA and DHA at the 1- and 3
      positions of TAGs does not result in their lower recovery in lymph. Processes
      after lipolysis may be responsible for their low recovery in lymph. In a separate
      study, slower lymphatic recovery of DHA given as free acid than TriDHA was
      improved by the simultaneous administration of TO, but not by free oleic acid.
      The observations suggest that the slow recovery of free acid is caused by delayed
      TAG synthesis in mucosal cells and/or low micellar solubility of fatty acids in
      the intestinal lumen due to a limited supply of 2-monoacylglycerol (MAG). A large
      portion of EPA and DHA were recovered in lymph chylomicrons and very low density
      lipoproteins (VLDL, > 95%) and incorporated into TAG (84-92%) fraction in all fat
      types examined. Lymphatic recovery rate of simultaneously administered
      cholesterol was influenced by the fat types given.

PMID- 8541339
TI  - Molecular cloning and expression of rat hepatic neutral cholesteryl ester
      hydrolase.
AB  - The 1923 bp cDNA for rat hepatic cholesteryl ester hydrolase (CEH) was cloned by
      screening a lambda gt11 expression library with an oligonucleotide containing the
      consensus active site sequence for cholesteryl esterases. Expression of a fusion
      protein, cross-reacting with antibody to the purified liver CEH, was demonstrated
      by Western blot analysis. The cDNA was sequenced and found to have only 44%
      homology with pancreatic CEH. Although unique, the cDNA sequence exhibited much
      greater overall homology with liver carboxylesterases, in both coding and 5'/3'
      non-coding regions. In Northern blot analysis, the cDNA hybridized with a single
      band from liver mRNA but not with pancreatic mRNA. The 1.7 kb coding sequence,
      predicting a 62 kDa protein, was cloned into an Escherichia coli expression
      system with an inducible promoter and into COS-7 cells. Both expression systems
      produced a protein which comigrated with liver CEH (66 kDa) on SDS-PAGE and
      immunoreacted with antibodies to liver CEH on Western blots. Whereas the
      prokaryotic system produced an inactive protein, expression in COS-7 cells was
      accompanied by a 5-fold increase in CEH activity and a corresponding increase in
      immunoreactive protein.

PMID- 8541340
TI  - Clofibrate treatment increases stearoyl-CoA desaturase mRNA level and enzyme
      activity in mouse liver.
AB  - Stearoyl-CoA desaturase activity is encoded by two highly homologous genes, SCD1
      and SCD2, which show tissue-specific expression and regulation. SCD1, which is
      expressed in the liver, showed a marked diurnal variation with the highest
      expression during the feeding period. Treatment of mice with the peroxisome
      proliferator clofibrate, which induces several lipid metabolizing enzymes,
      increased both the enzyme activity and mRNA level in the liver, indicating
      regulation at the transcriptional level. The highest expression of both SCD1 and
      SCD2 was found in brown adipose tissue, which was slightly down-regulated by
      feeding a fat-free diet.

PMID- 8541341
TI  - Platelet-activating factor receptor: gene expression and signal transduction.

PMID- 8541342
TI  - N-acetylgalactosamine-4-sulfatase: identification of four new mutations within
      the conserved sulfatase region causing mucopolysaccharidosis type VI.
AB  - Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome) is the lysosomal
      storage disorder resulting from the deficient activity of N-acetylgalactosamine-4
      sulfatase (arylsulfatase B; ASB). MPS VI has been described in man, cats and
      rats, and several mutations in the ASB gene have been identified in human
      patients and the animal models. Notably, ASB belongs to a family of sulfatases
      which are highly conserved, suggesting that they are related evolutionarily and
      functionally. In this manuscript, four new mutations causing MPS VI are described
      within the human ASB gene. Each of these mutations occurred in or near the
      hexapeptide 144GKWHLG149, one of the most highly conserved 'sulfatase' regions.
      In fact, three of the mutations occurred within the same codon, W146. Thus, these
      results provide new insights into the molecular lesions causing MPS VI and
      highlight the importance of this conserved sulfatase region.

PMID- 8541343
TI  - NMR studies of the effect of Mg2+ on post-ischemic recovery of ATP and
      intracellular sodium in perfused kidney.
AB  - Ischemia is often implicated as a cause of acute renal failure. We have
      investigated the effect of various concentrations of extracellular Mg2+ on the
      post-ischemic recovery of ATP and low intracellular Na+ in the isolated perfused
      rat kidney using 31P and triple-quantum filtered (TQ) 23Na-NMR spectroscopy.
      Following a 1 h period of stopped flow ischemia, the kidneys exposed to 0.3 mM
      Mg2+ throughout the experiment exhibited a significantly (p < 0.05) decreased
      post-ischemic fractional recovery of ATP (56 +/- 7%) as well as a significantly
      (p < 0.05) increased accumulation of P(i) (250 +/- 30%) as compared to kidneys
      exposed to 1.2 mM Mg2+ throughout (88 +/- 5% recovery of [ATP] and 158 +/- 8%
      accumulation of [P(i)]). Kidneys exposed to 0.3 mM Mg2+ during the pre-ischemic
      and ischemic periods but to 1.2 mM Mg2+ during reperfusion also showed better
      recovery of ATP (83 +/- 6%) and lower accumulation of P(i) (143 +/- 8%) compared
      to kidneys exposed to low Mg2+ (0.3 mM) throughout the experiment. Measurements
      of the 23Na TQ signal following ischemia-reperfusion revealed that kidneys
      exposed to 1.2 mM Mg2+ exhibited significantly improved maintenance of low
      intracellular Na+ as compared to those exposed to 0.3 mM Mg2+ ([Na+]i = 107 +/-
      7% in 1.2 mM Mg2+ vs. 152 +/- 3% in 0.3 mM Mg2+). No significant difference was
      found in the pre-ischemic basal intracellular free Ca2+ level (as measured by 19F
      NMR in combination with 5 FBAPTA) between kidneys perfused with 1.2 mM and 0.3 mM
      Mg2+, and comparable depletion of ATP occurred during ischemia under both
      experimental conditions. These data indicate that increased extracellular Mg2+
      has a protective effect against post-ischemic damage, probably related to its
      role in resynthesis of ATP during post-ischemic reperfusion. Our results would
      imply a greater vulnerability of the kidney to ischemic damage in hypomagnesemic
      clinical conditions such as alcoholism and diabetes.

PMID- 8541344
TI  - Immunochemical detection of protein adducts in cultured human hepatocytes exposed
      to diclofenac.
AB  - The non-steroidal anti-inflammatory drug diclofenac is reported to cause, in rare
      cases, fulminant hepatic necrosis associated with chronic use of the drug. In
      order to investigate the possibility that covalent protein adducts of reactive
      metabolites of diclofenac might be responsible for the hepatotoxicity produced by
      this drug, we developed an antibody against a diclofenac-keyhole limpet
      hemocyanin adduct. The anti-diclofenac antibody did recognize diclofenac-protein
      adducts on Western blots of homogenates of cultured human hepatocytes exposed to
      diclofenac. The major detected adduct was a 60 kDa protein, which was present in
      both human and rat hepatocytes. These results suggest that binding of diclofenac
      to human hepatocytes is, like in rats, selective and that a 60 kDa protein
      appears to be the major target for alkylation. Immunoblots of homogenates of
      liver sinusoidal lining cells (LSLC) from rats treated with diclofenac also
      exhibited adducts with a 60 kDa protein. This fact suggest a role for LSLC in
      processing of chemically altered proteins in the liver.

PMID- 8541345
TI  - Ubiquitin fusion proteins are overexpressed in colon cancer but not in gastric
      cancer.
AB  - A cDNA clone (AF3) encoding the ubiquitin A gene 52 amino acid extension fusion
      protein (UbA52) was isolated from a subtracted cDNA library of human colorectal
      carcinoma minus adjacent normal mucosa. In Northern hybridization the mRNA signal
      for UbA52 was greater in surgical samples of colonic carcinoma (T) than in paired
      adjacent normal (N) tissues in 24 of 29 cases (T/N = 3.4 +/- 0.5, P < 0.01). An
      oligonucleotide probe specific for only the 52 amino acid extension confirmed the
      overexpression of UbA52. In contrast, there was no overexpression of UbA52 mRNA
      in gastric cancer samples (n = 7, T/N = 1.0 +/- 0.3). The mRNA of several
      ribosomal proteins, and of another ubiquitin A gene fusion protein, UbA80, with
      an 80 amino acid extension of ribosomal protein S27a, have been reported to be
      over-expressed in colon cancer, but not as yet at the protein level. Using rabbit
      antisera to the ribosomal protein component S27a we demonstrate over-expression
      of S27a at the protein level in colonic (n = 5), but not gastric (n = 6)
      carcinomas. Therefore it is likely that both UbA80 and UbA52 are overexpressed in
      colon cancer, but not in gastric cancer.

PMID- 8541346
TI  - Control and kinetic analysis of ischemia-damaged heart mitochondria: which parts
      of the oxidative phosphorylation system are affected by ischemia?
AB  - We investigated the effects of ischemia on the kinetics and control of
      mitochondria isolated from normal and ischemic heart. The dependence of the
      respiratory chain, phosphorylation system and proton leak on the mitochondrial
      membrane potential were measured in mitochondria from hearts after 0, 30 min and
      45 min of in vitro ischemia. Data showed that during the development of ischemia
      from the reversible (30 min) to the irreversible (45 min) phase, a progressive
      decrease in activity of the respiratory chain occurs. At the same time an
      increase in proton leak across the mitochondrial inner membrane was observed.
      Phosphorylation is inhibited but seems to be less affected by ischemia than
      respiratory chain or proton leak. Control coefficients of the 3 blocks of
      reactions over respiration rate were determined in different respiratory states
      between state 4 and state 3. Ischemia caused the control exerted by the proton
      leak to increase in state 3 and the intermediate state and caused the control by
      the phosphorylation system to decrease in the intermediate state. Taken together,
      these results indicate that the main effects of ischemia on mitochondrial
      respiration are an inhibition of the respiratory chain and an increase of the
      proton leak.

PMID- 8541347
TI  - Molecular mechanism of the dysfunction of protein S(Tokushima) (Lys155-->Glu) for
      the regulation of the blood coagulation system.
AB  - The congenital abnormal protein S(Tokushima) has Glu substituted for Lys155 in
      the second epidermal growth factor domain of the protein S molecule (Hayashi T.,
      Nishioka J., Shigekiyo, T. Saito, S. and Suzuki, K. (1994) Blood 83, 683-690). To
      elucidate the molecular mechanism of the dysfunction of the protein S(Tokushima),
      a comparative evaluation between the molecular interaction of the abnormal
      protein S and that of normal protein S with other clotting factors was carried
      out using recombinant normal protein S (rPSN) and protein S(Tokushima) (rPST)
      expressed in baby hamster kidney cells. While rPSN and plasma protein S exhibited
      cofactor activity for activated protein C (APC), rPST did not show this property.
      rPSN and rPST bound equally to phospholipids and C4b-binding protein fixed on
      microplate wells. APC bound to rPSN but not to rPST in an assay using immobilized
      monoclonal anti-protein S antibody. On the other hand, rPSN and plasma protein S
      inhibited the activity of prothrombinase complex composed of factor Xa and
      thrombin-stimulated platelets, whereas rPST lacked this inhibitory effect.
      Assessment of the mechanism by which rPST lacks inhibitory activity on the
      platelet-prothrombinase complex was also performed. Factor Xa bound to rPSN but
      not to rPST. Binding to rPSN to biotinylated factor Va in solution phase did not
      differ significantly from that of rPST. Binding of prothrombin to factor Va in
      solution phase was not inhibited either by rPSN or rPST. Binding of 4
      amidinophenylmethanesulfonyl-factor Xa to factor Va in solution phase increased
      in the presence of rPSN but not in that of rPST. These findings suggest that the
      dysfunction of protein S(Tokushima) occurs because it fails to interact with APC
      and factor Xa. This molecular interaction is required for the expression of the
      APC cofactor activity and for the inhibition of the prothrombinase complex
      activity.

PMID- 8541348
TI  - Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation
      and a single base deletion are predominant in Japanese patients.
AB  - Holocarboxylase synthetase (HCS) deficiency is an inherited disease of biotin
      metabolism characterized by a unique pattern of organic aciduria, metabolic
      acidosis, and skin lesions. By analysis of five patients in four unrelated
      families, two mutations were identified: a transition from T to C which causes an
      amino-acid substitution of proline for leucine at position 237 (L237P) and a
      single deletion of guanine (delG1067) followed by premature termination. One
      patient was homozygous for the L237P mutation, three patients in two families
      were compound heterozygotes of the missense and deletion alleles, and the other
      patient was heterozygous for the L237P mutation. Inheritance was successfully
      demonstrated in all of the patients' families by a modified PCR followed by
      restriction enzyme digestion. The two mutations accounted for seven of eight
      mutant alleles, while neither mutation was detected in 108 normal healthy
      Japanese children (216 alleles). Transient expression in cultured fibroblasts
      from a patient showed that the L237P mutation was responsible for decreased HCS
      activity. These results suggest that the L237P and delG1067 mutations are
      frequent disease-causing mutations in Japanese patients with HCS deficiency. This
      PCR-based technique may therefore be useful for detecting mutations among
      Japanese patients.

PMID- 8541349
TI  - Hydrogen peroxide metabolism during peroxisome proliferation by fenofibrate.
AB  - Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was given to
      mice (0.23% w/w in the diet) during 1-3 weeks and enzyme activities, H2O2
      concentration, and H2O2 production rate were determined. A maximal increase of
      150% in liver/body weight ratio was observed after 3 weeks of treatment. Acyl-CoA
      oxidase, catalase and uricase activities were increased by 712%, 506% and 41%
      respectively by treatment with fenofibrate. Se- and non Se-glutathione peroxidase
      and Mn-superoxide dismutase activities were increased by 331%, 188% and 130%
      respectively in the liver of 2 weeks-treated mice. Cu-Zn superoxide dismutase
      activity was not affected by fenofibrate treatment. H2O2 steady-state
      concentration showed an increase of 89% after 2 weeks of treatment. H2O2
      production rates, and the steady-state concentrations of the intermediates HO, R
      and ROO, calculated using experimental data, were higher in the liver of
      fenofibrate-treated mice than in control animals. According to our findings, the
      imbalance between H2O2 production and its degradation by its metabolizing enzymes
      during peroxisome proliferation, would result in an increased level of H2O2
      steady-state concentration, with the resulting oxidative stress which may lead to
      the generation of oxidative damage and to the induction of liver carcinogenesis.

PMID- 8541351
TI  - Scavenging of neutrophil-derived superoxide anion by 1-hydroxyphenazine, a
      phenazine derivative associated with chronic Pseudomonas aeruginosa infection:
      relevance to cystic fibrosis.
AB  - The airways of cystic fibrosis patients colonised by Pseudomonas aeruginosa
      contain the redox active phenazine derivative, 1-hydroxyphenazine (OHP). As the
      presence of reactive oxygen species is of importance to tissue damage in cystic
      fibrosis, OHP was investigated for its ability to reduce molecular oxygen to
      superoxide. In the presence of NADPH, OHP reduced cytochrome c in a dose
      dependent manner. This effect was not inhibited by superoxide dismutase and
      demonstrates an electron transport role for OHP. The OHP/NADPH system was unable
      to reduce molecular oxygen to superoxide as judged by an inability to oxidase
      epinephrine to adrenochrome. However, using lucigenin-enhanced chemiluminescence
      to detect superoxide, it was found that pathophysiologically relevant
      concentrations of OHP (5-25 microM) effectively scavenged superoxide from a
      xanthine/xanthine oxidase system. Similarly, in the presence of OHP, superoxide
      availability from contact-activated neutrophils was substantially reduced. It is
      concluded that OHP is an efficient scavenger of superoxide and that electron
      transfer from superoxide to OHP represents a major mechanism for reduction of OHP
      in vivo. Reduced OHP has the potential to alter cellular function by
      participating in the reduction of iron-containing proteins and in this manner
      contribute to the pathogenesis of P. aeruginosa infection in cystic fibrosis.

PMID- 8541350
TI  - Laser-excited fluorescence studies of mitochondrial function in saponin-skinned
      skeletal muscle fibers of patients with chronic progressive external
      ophthalmoplegia.
AB  - The functional behavior of mitochondria in skeletal muscle of patients with
      chronic progressive external ophthalmoplegia was studied by laser-excited
      fluorescence measurements of NAD(P)H and flavoproteins in saponin-skinned fibers.
      Variations in the mitochondrial content and the presence of partially respiratory
      chain-inhibited mitochondria can be detected using this novel method.

PMID- 8541352
TI  - Assembly of mitochondrial ATP synthase in cultured human cells: implications for
      mitochondrial diseases.
AB  - To study the assembly of mitochondrial F1F0 ATP synthase, cultured human cells
      were labeled with [35S]methionine in pulse-chase experiments. Next, two
      dimensional electrophoresis and fluorography were used to analyze the assembly
      pattern. Two assembly intermediates could be demonstrated. First the F1 part
      appeared to be assembled, and next an intermediate product that contained F1 and
      subunit c. This product probably also contained subunits b, F6 and OSCP, but not
      the mitochondrially encoded subunits a and A6L. Both intermediate complexes
      accumulated when mitochondrial protein synthesis was inhibited, suggesting that
      mitochondrially encoded subunits are indispensable for the formation of a fully
      assembled ATP synthase complex, but not for the formation of the intermediate
      complexes. The results and methods described in this study offer an approach to
      study the effects of mutations in subunits of mitochondrial ATP synthase on the
      assembly of this complex. This might be of value for a better understanding of
      deficiencies of ATP synthase activity in mitochrondrial diseases.

PMID- 8541353
TI  - 19-Allylaminoherbimycin A, an analog of herbimycin A that is stable against
      treatment with thiol compounds or granulocyte-macrophage colony-stimulating
      factor in human leukemia cells.
AB  - Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular
      phosphorylation by some protein tyrosine kinases and inhibits the proliferation
      of malignant cells which express high tyrosine kinase activity. Herbimycin A
      inhibited the proliferation of human monoblastic leukemia U937 cells, but this
      inhibition was abrogated by the addition of granulocyte-macrophage colony
      stimulating factor (GM-CSF). On the other hand, a derivative of herbimycin A, 19
      allylaminoherbimycin A, inhibited the proliferation of such cells without
      interference by the addition of GM-CSF. Phosphorylation of MAP kinase and c-myc
      expression induced by GM-CSF in U937 cells were inhibited by both herbimycin A
      and 19-allylaminoherbimycin A. The time courses of growth inhibition showed that
      the growth-inhibitory activity of herbimycin A in U937 cells was initially
      potent, but gradually decreased in the presence of GM-CSF. Thiol compounds,
      glutathione (GSH) and 2-mercaptoethanol, abrogated the inhibition of the growth
      of U937 cells by herbimycin A, but not by 19-allylaminoherbimycin A, like GM-CSF.
      Intracellular GSH content in U937 cells was increased by treatment with GM-CSF,
      and decreased with herbimycin A, but returned to the control level with the
      addition of GM-CSF to herbimycin A. In thin-layer chromatography, after in vitro
      incubation with herbimycin A and GSH, nothing could be detected at the position
      of intact herbimycin A, while 19-allylaminoherbimycin A was stably detected.
      These findings suggest that changes in the intracellular concentration of GSH
      play a role in the abrogation of the inhibition of U937 cell growth by herbimycin
      A. In the presence of GSH, 19-allylaminoherbimycin A inhibited the proliferation
      of U937 cells and Philadelphia chromosome-positive K562 cells more effectively
      than herbimycin A. Since GSH plays a role in detoxicating several anticancer
      drugs, 19-allylaminoherbimycin A may have therapeutic advantages over herbimycin
      A against some types of leukemia.

PMID- 8541354
TI  - Reliability of interview responses of injecting drug users.
AB  - We compared 23 injecting drug users (IDUs) who were part of a larger study at
      retest periods of less than or greater than one month for test-retest reliability
      of their responses to a detailed questionnaire covering demographics, drug use,
      HIV risk behavior and attitudes and knowledge about HIV. Data indicated that
      there was high test-retest reliability for demographic characteristics, and for
      the social context of drug use for the shorter retest duration.

PMID- 8541355
TI  - Addiction medicine: definition of the specialty through definition of the
      practice.

PMID- 8541356
TI  - Four years experience of a hospital's impaired physician committee.
AB  - Physician impairment contributes to patient morbidity, malpractice claims,
      physician license loss and suicide. This paper describes four years of experience
      of the University of Maryland's Professional Assistance Committee. The committee
      is composed of medical staff members. Its mission is to help impaired physicians
      obtain assessment, treatment and monitoring, and to protect patients from harm.
      The committee has evaluated 23 cases over the past four years. Ten were
      credential checks, and 13 investigations of active problems. Eight of the 23
      cases were for alcohol, eight for drug, and seven for behavioral problems. Only
      one person lost medical staff privileges. The committee has been well accepted by
      the medical staff and hospital administration and can be easily reproduced in
      other hospitals.

PMID- 8541357
TI  - Determining priorities for family physician education in substance abuse by the
      use of a survey.
AB  - As the initial stage in developing a curriculum to assist family physicians to
      diagnose and manage alcohol abuse in their practices, questionnaires were mailed
      to a selected group of family physicians. A total of 117 physicians (34%)
      completed the questionnaire. The majority of physicians (70.1%) reported that
      fewer than 10% of their caseload experienced alcohol-related problems. Most
      physicians (59.3%) did not use any of the standard diagnostic instruments but
      reported that screening and detection was the most challenging alcohol-related
      problem along with patient management. The questionnaire identified a number of
      areas that could be used in the development of educational strategies to increase
      the expertise of primary care physicians in the diagnosis and management of
      alcohol-related problems.

PMID- 8541358
TI  - Community based heroin addicts who turn to experimental treatment rather than
      conventional care.
AB  - In this paper we report on a community based sample of heroin addicts not in
      addiction treatment who responded to the offer of experimental treatment
      (buprenorphine) for heroin addition. Comparison to a sample of methadone
      maintenance clients from the same geographic area reveals that on average the
      community sample began heroin use later, attained a higher level of education,
      and were most likely to have had a significant cohabitation relationship. The
      methadone maintenance sample, on the other hand, reported significantly greater
      regular use of drugs of abuse other than heroin. Each group may represent a
      different subgroup drawn from the heterogeneous heroin-addicted population.
      Implications for improved recruitment into treatment and enhanced treatment
      design are drawn from these findings.

PMID- 8541359
TI  - Marital status, alcohol abuse and attempted suicide: a logit model.
AB  - Research on suicide and marital status has neglected the impact of alcohol abuse.
      Given that nonmarried people are more apt to abuse alcohol than married people,
      the often cited relationship between low marital integration and suicide may
      either be spurious, or it may involve a complicated interaction between the two
      variables. Married individuals consume less alcohol than unmarried individuals,
      but within marriage alcohol abuse does occur, and when it leads to family abuse
      it may trigger suicide. Also, over the life course individuals experience
      stressors (e.g., unemployment, illness) that may influence alcohol abuse and
      suicide. The present study explores the causal linkage between marital status,
      alcohol abuse and suicide at the micro level, employing data from the
      Epidemiological Catchment Area surveys. Logistic regression results indicate that
      marital status affects the odds of attempting suicide independent of indicators
      of alcohol abuse. Alcohol abuse is, however, a better predictor of attempted
      suicide than marital status.

PMID- 8541360
TI  - A pilot study of factors associated with resilience to substance abuse in
      adolescent sons of alcoholic fathers.
AB  - This pilot study evaluated the association between substance abuse outcome and
      putative protective factors in sons of alcoholic fathers. A battery of
      questionnaires was anonymously self-administered to 24 sons of alcoholic fathers
      ages 16-19 years to identify relationships between alcohol and/or drug abuse and
      factors hypothesized to be related to parental alcoholism. Of the 24 subjects, 13
      were categorized through self-identification and self-report screening measures
      as having alcohol and/or drug problems and 11 were categorized as not having
      substance abuse problems. Boys without substance problems: (1) had significantly
      higher maternal occupational status (p = .01); (2) experienced more good life
      events (p < .001), and (3) had a more internally oriented locus of control (p <
      .001). Good events and internal locus of control were highly correlated with each
      other (r = .620, p < .01). The fact that these preliminary findings are
      consistent with other literature despite marked methodologic and sample
      differences indicates that these putative components of resilience are robust and
      deserve further study towards improved substance abuse prevention in those at
      high risk.

PMID- 8541361
TI  - The use of sodium valproate in the treatment of alcoholism.
AB  - It has been suggested that decreased central GABAergic activity may play a role
      in the pathogenesis of alcoholism. Sodium valproate is a commercially available
      anticonvulsant that increases central GABAergic activity. In this pilot study 13
      adult male alcoholics received one month of oral, low dose sodium valproate (15
      mg/kg/d) followed by one month of placebo followed by one month of sodium
      valproate at the standard anticonvulsant dosage (45 mg/kg/d). The principle
      objective of the study was to determine if sodium valproate is well tolerated and
      free of adverse effects in this high risk group. Anxiety levels and the desire to
      drink alcohol were also monitored throughout the study period. The results of the
      study revealed that low dose sodium valproate therapy is well tolerated and free
      of toxicity. While anxiety levels tended to fall or remained unchanged in the
      seven patients who completed four weeks of low dose treatment, there was no
      consistent change in their desire to drink values. Too few patients completed the
      trial to ascertain the safety or efficacy of standard dose sodium valproate.
      These findings suggest that controlled clinical trials of sodium valproate are
      feasible in adult male alcoholics.

PMID- 8541362
TI  - Assessment of family history of alcoholism in sons of alcoholic fathers.
AB  - Results of studies of sons of alcoholics (SOAs) may vary depending on the density
      of the family history of alcoholism of the SOA subjects selected. To assess how
      reliably SOA subjects report a history of alcoholism in first- and second-degree
      relatives, we compared family histories obtained from 20 SOAs with those provided
      by their fathers. In all 20 cases, SOAs and their fathers agreed that the father
      met criteria for alcohol dependence but for no other primary Axis I psychiatric
      disorder. However, agreement was not as good for whether other paternal relatives
      in addition to the father were affected (kappa = 0.36) or for whether the family
      history was unigenerational or multigenerational for alcoholism (kappa = 0.44).
      Whether this discrepancy was due to under-reporting by the son or over-reporting
      by the father is unclear. These results suggest that 18-25 year old SOAs are
      reliable sources regarding alcohol dependence in their fathers, but that for
      determination of density of the family history of alcoholism, other relatives
      should also be interviewed directly.

PMID- 8541363
TI  - Selective guide to current reference sources on topics discussed in this issue.

PMID- 8541364
TI  - Public policy statement on inquiring into physicians' health on applications for
      licensure, examination and privileges.

PMID- 8541365
TI  - Public policy statement on mutually accepted sanctions by State Boards of Medical
      Examiners.

PMID- 8541366
TI  - Safe play for osteoporosis?

PMID- 8541367
TI  - Prevention and treatment of osteoporosis.
AB  - Because the lifetime risk of fragility fracture for a 50-year-old Caucasian woman
      is about 40 per cent, a whole-life strategy of osteoporosis prevention is
      necessary. In childhood, primary prevention of osteoporosis is based on exercise
      and adequate dietary calcium. In women undergoing menopause, hormone replacement
      therapy administered for at least ten years remains the preventive treatment of
      choice, and is associated with a substantial reduction in vertebral and non
      vertebral fractures. Intranasal salmon calcitonin and bisphosphonates are
      effective alternatives, but their effects on fracture rate and their long-term
      safety require further evaluation. Regarding the prevention of the late bone loss
      leading to senile osteoporosis, there is now evidence that the reduction of the
      secondary hyperparathyroidism induced by calcium and vitamin D insufficiencies
      through the administration of calcium and vitamin D supplements significantly
      decreases the hip fracture incidence. There is no general consensus about the
      efficacy of treatment for established osteoporosis with fractures. Fluoride salts
      have proven their direct stimulating effects on bone formation; dosage must be
      moderate, and the duration of treatment should be limited to 2-3 years in order
      not to impair the quality of the new bone. Cyclical therapy with etidronate
      induces beneficial effects on bone mass in the spine, but its effect on the
      vertebral fracture rate is not yet established. The new bisphosphonates seem to
      be promising for the management of osteoporosis. Several other agents such as
      growth factors, silicon derivatives and strontium salts are in various stages of
      testing. The new definition of osteoporosis proposed by a WHO study group, no
      longer based on the fracture but on a low bone mass, is of major interest,
      because it should make possible to have a more effective therapeutic approach,
      before the occurrence of an irreversible degree of bone loss.

PMID- 8541368
TI  - The Adelaide Activities Profile: a measure of the life-style activities of
      elderly people.
AB  - A new instrument for the measurement of life-style activities of the elderly is
      described. The Adelaide Activities Profile (AAP) was developed in response to the
      shortcomings of the Frenchay Activities Index. The AAP was validated on a random
      sample of 1799 people aged 70 years and over, living outside of institutional
      care. Principal components factor analysis revealed four consistent factors from
      which four scales were derived; these scales were named domestic chores,
      household maintenance, service to others, and social activities. Analyses
      demonstrated the construct validity of the four life-style scales by showing them
      to be differentially sensitive to a range of domestic, health and social
      circumstances. It was concluded that the distinct and meaningful clusters of
      activities represented by the AAP scales should have broad application as health
      and social indicators.

PMID- 8541369
TI  - Apolipoprotein E allele frequencies in an Italian population: relation to age and
      lipid profile.
AB  - Apo E phenotype and plasma Tg, Chol, LDL-Chol, HDL-Chol and Apo B levels were
      determined in a sample of 228 healthy Italian subjects (124 men and 104 women)
      aged 18-93. The allele frequencies were: epsilon 2 = 0.070; epsilon 3 = 0.829;
      epsilon 4 = 0.101 (among the lowest values in the literature). Division of the
      sample into four age groups indicated that epsilon 4 frequency decreased with age
      to 0 in persons aged over 75. Covariance analysis of the influence of each allele
      on plasma lipids showed that epsilon 4 was significantly associated with the
      highest Chol, LDL-Chol and Apo B levels. These data are evidence of the influence
      of epsilon 4 on Chol metabolism in an Italian population. They also show that its
      frequency decreases with age.

PMID- 8541370
TI  - Colonic investigations in the elderly: colonoscopy or barium enema?
AB  - Colonoscopy (CS) is currently considered the best diagnostic procedure for
      colonic imaging. The objectives of this multicentric study were to assess whether
      CS or simple contrast barium enema (SCBE) has the best effectiveness and
      tolerance in the elderly (over 80 years old). Except in cases of emergency, 67
      elderly patients from 3 centers were randomized among three diagnostic
      strategies: CS, SCBE or barium enema+rectosigmoidoscopy (BERS). CSs were
      generally carried out after polyethylene-glycol (PEG) cleansing, and barium
      enemas after enema cleansing. The diagnostic effectiveness of the three
      strategies was not significantly different: a colonic abnormality was found in
      CS, SCBE, BERS groups in 65, 56 and 71% of the cases, respectively. No other
      investigation was needed in 61 to 76% of cases, and, on the basis of the
      exploration, final therapy was modified in less than 22% of cases. Overall
      cleansing quality was significantly better with barium enema (84.1%) than with CS
      (57.0%; p < 0.05). This was explained by a poor tolerance to PEG intake, which
      led to 28.2% of adverse effects, compared with 7.1% after enema preparation (p <
      0.05). This resulted in a significantly higher failure rate of complete colonic
      exploration with CS (48%) than with barium enema (9%; p < 0.001). In conclusion,
      the effectiveness of the three diagnostic strategies is similar in the elderly.
      However, due to a better acceptance of the enema preparation, and to a better
      success rate of complete exploration, SCBE should be preferred to investigate
      colonic symptoms when the above preparations are used.

PMID- 8541371
TI  - Psychomotor speed and physical activity in 75-year-old residents in three Nordic
      localities.
AB  - Psychomotor speed was studied in samples of 75-year-old men and women in three
      Nordic localities, namely Glostrup (Denmark), Gothenburg (Sweden), and Jyvaskyla
      (Finland). Both simple and multi-choice reaction and movement time tests were
      applied using visual and auditory stimuli. The aim of the present report was to
      analyze the role of habitual physical activity and physical fitness as associates
      of psychomotor speed. The results indicated a higher psychomotor speed in the
      physically more active and, in most cases, fitter subjects in both the simple and
      more complex tasks, a higher speed of performance in men compared to women, and,
      to some extent, more favorable values in Gothenburg and Jyvaskyla than in
      Glostrup. The overall findings suggest that habitual physical activity may
      enhance psychomotor speed in elderly subjects. Basic differences in activity did
      not, however, explain the differences in psychomotor speed observed between the
      localities or between the sexes.

PMID- 8541372
TI  - Reduced left ventricular mechanical efficiency in elderly patients with coronary
      artery disease.
AB  - We evaluated left ventricular (LV) mechanical efficiency in 23 elderly patients
      (mean age 67 +/- 2) with coronary artery disease (CAD) and in 22 patients younger
      than 65 years (mean age 49 +/- 8) with similar severity of CAD (2.4 +/- 0.8 and
      2.2 +/- 0.8 vessels per patient, respectively) and history of myocardial
      infarction (34% and 41%, respectively). LV mechanical efficiency was calculated
      as the ratio of LV work per minute and myocardial O2 consumption. LV stroke
      volume was calculated from left ventriculography. Coronary blood flow was
      measured by thermodilution. Older patients had lower values of LV stroke volume
      (49 +/- 16 vs 73 +/- 16 mL, p < 0.005), ejection fraction (41 +/- 17 vs 58 +/-
      17%, p < 0.05), LV stroke work (93 +/- 26 vs 131 +/- 41 g.m., p < 0.02) and LV
      work per minute (6.7 +/- 2.6 vs 9.3 +/- 2.7 kg.m./min, p < 0.05). Since
      myocardial O2 consumption was similar in the two groups, LV mechanical efficiency
      was lower in older CAD patients (16.2 +/- 15 vs 23.8 +/- 12%, p < 0.05). Thus,
      elderly patients with CAD show a reduced LV mechanical pump performance and
      efficiency, compared with younger patients with similar disease severity and
      history of myocardial infarction. These observations may contribute to
      understanding the higher frequency of congestive heart failure in elderly
      patients with CAD.

PMID- 8541373
TI  - Effect of age on cardiac norepinephrine release in the female rat.
AB  - We previously demonstrated an age-related decline in K(+)-induced norepinephrine
      (NE) release from cardiac synaptosomes prepared from 6- and 24-month-old male
      F344 rats. The purpose of the present study was to determine if the age-related
      decrease in NE release seen in male F344 rats is also present in female F344
      rats. K(+)-induced NE release was assessed in cardiac synaptosomes prepared from
      6-, 12-, 18-, and 24-month-old male and female F344 rats. NE release was
      significantly greater in young male rats, compared to old male rats. However, no
      age-related decrease in NE release was observed in the female rats. In contrast
      to previous observations in male rats, raising extracellular [Mg2+], an inorganic
      Ca2+ channel blocker, reduced NE release to the same extent in all female ages.
      Omega-conotoxin, an organic Ca2+ channel blocker, also decreased NE release to
      the same extent in all female ages. These studies suggest that in contrast to
      aging male rats, cardiac adrenergic nerve terminals of aging female rats maintain
      their capacity to release NE.

PMID- 8541374
TI  - Prevalence of autoantibodies in the very elderly: association with symptoms of
      ischemic heart disease.
AB  - The mechanisms leading to the increased expression of autoantibodies in the
      elderly are poorly understood. The aim of this study was to investigate whether
      the presence of ischemic heart disease (IHD) is associated with the prevalence of
      autoantibodies in the elderly over 85 years of age. Anti-nuclear (ANA), anti
      smooth muscle (SMA), anti-mitochondrial (AMA), thyroid anti-microsomal
      autoantibodies (anti-Tg) and antibodies to gastric parietal cells (PCA) were
      determined in selected groups of healthy subjects and patients with IHD. In IHD
      patients, the following autoantibodies were detected: ANA in 42.1% of subjects,
      SMA in 10.5%, AMA in 5.3%, anti-Tg in 5.3%, and PCA in 5.3%. In control healthy
      subjects, ANA were detected in 10%, AMA in 5%, and PCA in 15%. In conclusion,
      autoantibodies were more common in patients with IHD than in control healthy
      subjects, but no significant differences were found.

PMID- 8541375
TI  - Outcome of elderly patients requiring ventilatory support in intensive care.
AB  - The objectives of the study were: 1) to evaluate mortality in elderly patients
      requiring ventilatory support in Intensive Care Unit (ICU) and at 6, 12 and 18
      months after discharge from ICU; 2) (main objective) to determine predictors of
      mortality in ICU and after discharge; and 3) to assess the life-style of
      survivors. One hundred and ten consecutive hospitalized patients > or = 70 years
      were included in this retrospective study. Follow-up evaluation was conducted by
      telephone interview. Mortality in ICU and after discharge was the outcome
      variable. Fifteen parameters were recorded at admission and during
      hospitalization. Residence, health status, and self-sufficiency were evaluated
      after discharge. 1) Mortality in ICU and at 6, 12 and 18 months after discharge
      was 38%, 60%, 63% and 67% respectively. 2) The predictors of mortality in ICU
      were admission in shock, and use of major therapeutic interventions. Predictors
      of mortality at 6 months were admission in shock, previous impaired health status
      and marital status. 3) Eighteen months after discharge 92% of the surviving
      patients (N = 33) had the same residence, 75% had the same health status, and 78%
      had the same autonomy compared with pre-admission status. We concluded that shock
      and previous health status but not age are predictors of short- and long-term
      prognoses in elderly patients hospitalized in ICU for mechanical ventilation.

PMID- 8541376
TI  - Classifying change with the Sickness Impact Profile for Nursing Homes (SIP-NH).
AB  - The aim of this cohort study was to evaluate the concordance of the Sickness
      Impact Profile for Nursing Homes (SIP-NH) and Sickness Impact Profile (SIP) in
      classifying change. Subjects consisted of 194 consecutive long-stay nursing home
      residents at one academic department of the V.A. and in 8 community proprietary
      nursing homes in San Antonio, Texas. They were to have more than 3 months
      residency; to be > or = 61 years; and to be dependent in at least 2 ADLs with an
      MMSE score of > or = 15. Subjects were administered a 128-item SIP and a reduced
      66-item SIP-NH at baseline and 4, 8, and 12-month follow-up. At each follow-up,
      subjects were classified into 3 mutually exclusive change categories using a
      change score of > or = 5 points. Concordance of the classification of subjects by
      the SIP-NH and SIP was evaluated. The misclassification rate as well as its
      direction was also assessed. Both instruments classified a little over one
      quarter of the subjects as better, over a third as being unchanged, and another
      third as being worse at the four-month follow-up. More subjects were classified
      as worse by both instruments at 8 and 12 months. All kappas ranged from 0.52 to
      0.78, indicating good to excellent agreement. Overall, the SIP-NH characterized
      persons as changed more often than the SIP with no systematic directional bias.
      In conclusion, the SIP-NH was concordant with the SIP in classifying change in
      subjects. However, we cannot say which of the two is better for detecting change.
      Future research must focus on defining a change score which has clinical meaning,
      and evaluate responsiveness to change.

PMID- 8541378
TI  - Lymphoma.

PMID- 8541377
TI  - The effect of aging on oro-cecal transit time in normal subjects and patients
      with gallstone disease.
AB  - To ascertain whether aging and/or cholelithiasis can influence oro-cecal transit
      time (OCTT), we studied a total of 70 subjects, i.e., 10 healthy young adult
      controls, 22 healthy elderly controls, 18 elderly cholelithiasis patients and 20
      elderly subjects with a history of cholecystectomy for gallstones. OCTT was
      measured by means of the hydrogen breath test after administering a liquid meal
      of 10 g of lactulose in 200 mL of water, and collecting exhaled breath samples
      every 10 minutes for 200 minutes. Of all subjects in the group of patients with a
      history of cholecystectomy, 6/20 were non-hydrogen producers, and therefore were
      not included in the study. The OCTT was found to be significantly longer in
      healthy elderly controls, than in healthy young adult controls; the elderly
      subjects who had undergone cholecystectomy had a longer OCTT than the healthy
      elderly controls, while no difference was detected when compared to elderly
      patients with gallstones. In conclusion, OCTT seems to increase in healthy aging.
      Cholecystectomy also increases OCTT in the elderly, suggesting a link between
      intestinal motility and the biliary tract which may be of pathophysiological
      significance.

PMID- 8541379
TI  - Cancer in AIDS.

PMID- 8541380
TI  - Gynecologic cancer.

PMID- 8541381
TI  - Cancer prevention: new challenges and opportunities.

PMID- 8541382
TI  - Lymphoma.

PMID- 8541383
TI  - Revised European-American Lymphoma Classification.
AB  - The recently proposed Revised European-American Lymphoma Classification
      represents a serious attempt to overcome the controversies that have divided both
      pathologists and clinicians over the past three decades. It was formulated by 19
      experienced hematopathologists, who agreed on a list of clinicopathologic
      entities, all well known from the literature and daily practice. Compared with
      previous schemes, the Revised European-American Lymphoma Classification offers
      the following advantages: 1) it incorporates all nodal and extranodal lymphoid
      tumors, including Hodgkin's disease; 2) it is histogenetically updated by
      recognizing new categories (such as the mantle cell category) and grouping tumors
      that need further validation to be considered as separate entities (eg, diffuse
      large B-cell lymphomas); 3) it avoids any morphologic grading, the clinical
      course of lymphomas being influenced by factors other than histology (tumor
      burden, cell kinetics, apoptotic rate, and so forth) and 4) it includes all
      molecular data (phenotype, genotype, cytogenetics, and so forth), which can
      assist in the diagnosis.

PMID- 8541384
TI  - New insights into peripheral T-cell lymphomas.
AB  - Peripheral T-cell lymphomas comprise a morphologically diverse group of malignant
      lymphoproliferative disorders that arise from postthymic T cells. Currently,
      there exists no universally accepted system of classification of peripheral T
      cell lymphoma. Recent efforts to elucidate pathogenetic mechanisms and define
      recognizable entities have begun to clarify the nature of these tumors. These and
      future studies may one day lead to a unified system of classification of
      peripheral T-cell lymphoma that is reproducible, biologically relevant, and more
      predictive of clinical behavior and prognosis.

PMID- 8541385
TI  - Mucosa-associated lymphoid tissue lymphomas.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct subgroup of non
      Hodgkin's lymphoma with a particular clinicopathologic behavior. The
      gastrointestinal tract is involved in two thirds of the cases, but it may be
      observed in lung, breast, bladder, conjunctiva, kidney, liver, skin, salivary
      glands, thyroid, and thymus. This type of lymphoma tends to appear in patients
      with a history of autoimmune disease or chronic inflammatory disorders. In the
      stomach, this lesion is induced by Helicobacter pylori and is characterized by an
      accumulation of lymphoid tissue leading to chronic gastritis. The preceding
      lymphoid disorder is represented by Sjogren's syndrome, Hashimoto thyroiditis,
      and interstitial lymphoid pneumonia in the thyroid, salivary glands, or lung,
      respectively. Lymphoma cells initially arise from the marginal zone localized
      around reactive follicles and secondarily invade epithelial tissue to form the
      characteristic lymphoepithelial lesion. Patients with gastrointestinal MALT
      lymphoma generally present with localized disease without any adverse prognostic
      factors. These patients have long survival rates. Recurrences may appear in the
      same organ or in other extranodal sites. Nongastrointestinal MALT lymphoma
      patients seem to have a similar outcome. Patients may be treated with surgery or
      radiotherapy if the disease is localized, or with single-agent chemotherapy if it
      is disseminated. Reversion of the chronic inflammatory disorder with antibiotics,
      such as for gastric involvement, is a new observation that may change therapeutic
      options in the future.

PMID- 8541386
TI  - Current role of radiotherapy in Hodgkin's and non-Hodgkin's lymphoma.
AB  - Current goals of therapy for patients with Hodgkin's disease include maximizing
      cure rate while minimizing toxicity, particularly long-term toxicity such as
      treatment-related second cancers, pulmonary toxicity, and cardiac toxicity. For
      early-stage patients the need for staging laparotomy, the necessary extent of
      radiation therapy, and the possibilities of combined modality therapy are current
      controversies. For patients with stage III disease it is now clear that
      chemotherapy is an essential component of therapy. Long-term follow-up studies
      continue to show that a significant number of patients treated for Hodgkin's
      disease eventually develop solid tumors and acute myelogenous leukemia.
      Populations most at risk and treatments associated with these risks are being
      defined. For patients with large-cell lymphoma, anthracycline-containing
      chemotherapy is the mainstay of therapy, although radiation therapy to sites of
      bulky disease may have a role.

PMID- 8541387
TI  - Cancer in AIDS.

PMID- 8541388
TI  - Treatment strategies for epidemic Kaposi's sarcoma.
AB  - As the AIDS epidemic progresses, Kaposi's sarcoma continues to contribute
      substantially to the morbidity suffered by AIDS patients. Advances in our
      understanding of the pathogenesis of Kaposi's sarcoma have resulted in treatment
      strategies that are being investigated in the laboratory and clinic. Agents that
      affect the abnormal cytokines associated with Kaposi's sarcoma or inhibit
      angiogenesis are in early clinical trials. The recent discovery of a putative
      Kaposi's sarcoma virus may lead to new preventive or therapeutic strategies.
      Interferon, usually in combination with an antiretroviral nucleoside analogue,
      remains an important therapeutic option for patients with relatively intact
      immune function. For patients with more advanced immune suppression, chemotherapy
      is usually given, although there is no standard treatment regimen. New
      chemotherapeutic agents, including the use of liposomal encapsulated
      anthracyclines and topoisomerase-1 inhibitors, are being evaluated.

PMID- 8541389
TI  - Human papillomavirus-associated malignancies in HIV-positive men and women.
AB  - Human papillomavirus (HPV) infections of the anogenital tract and HPV-associated
      anogenital neoplasia are commonly found in HIV-positive men and women. Although
      there is little evidence suggesting that the incidence of invasive cervical
      cancer is increased in HIV-positive women, the incidence of invasive anal cancer
      may be increased in HIV-positive men. Among HIV-positive women, cervical
      intraepithelial neoplasia progresses more rapidly and recurs more often after
      primary therapy than in HIV-negative women. HPV infection and HPV-associated
      disease are often multifocal in HIV-positive women, and they may be found in both
      the vulva and the anus. Cervical cytology appears to be adequate as a screening
      tool for cervical intraepithelial neoplasia in HIV-positive women, but the high
      recurrence rate and multifocal nature of this disease reinforces the need for
      careful evaluation and follow-up of the entire anogenital tract in these women.

PMID- 8541390
TI  - Treatment of AIDS-related lymphomas.
AB  - Infection with HIV is associated with an increased risk of systemic and primary
      central nervous system non-Hodgkin's lymphoma. Patients with systemic non
      Hodgkin's lymphoma usually present with high- or intermediate-grade histology and
      extranodal dissemination. Although the prognosis for such patients is poor, some
      patients clearly benefit from combination chemotherapy, and several new treatment
      approaches appear promising. Primary central nervous system lymphoma usually
      occurs in patients with more profound immunosuppression and is associated with a
      dismal prognosis. Selected patients with good performance status may benefit from
      therapy, particularly if opportunistic infections have been few and
      nondebilitating. Finally, Hodgkin's disease has been reported in patients with
      HIV infection, particularly in patients with a history of intravenous drug use,
      and it is more likely to present with advanced-stage disease and unfavorable
      histology.

PMID- 8541391
TI  - An integrated approach to the epidemiology of Kaposi's sarcoma.
AB  - As an AIDS-defining illness, Kaposi's sarcoma primarily occurs among HIV-infected
      homosexual men in developed countries and among men and women in Africa. Except
      in Africa, Kaposi's sarcoma was rarely diagnosed prior to the AIDS epidemic. The
      clustering of cases geographically and by gender suggest an environmental
      influence. Epidemiologic evidence of an infectious cofactor for the disease is
      presented with the recent findings of herpetic-like viral DNA in Kaposi's sarcoma
      tissue. Observations indicate that this putative cofactor is sexually
      transmitted. A model is provided that integrates the virologic and epidemiologic
      components in the etiology of Kaposi's sarcoma.

PMID- 8541392
TI  - Chemotherapy for gynecologic malignancies.
AB  - Platinum-based chemotherapy is still the cornerstone in the chemotherapeutic
      approach of ovarian cancer patients. Recent advances include the introduction of
      paclitaxel in first-line chemotherapy and the demonstrated importance of
      administering cisplatin intraperitoneally in patients with small-volume disease.
      DNA repair and apoptosis are increasingly recognized as important processes
      involved in resistance to chemotherapy. Tamoxifen use is associated with a higher
      risk of endometrial cancer, with duration and cumulative dose of tamoxifen as
      additional factors. Hormonal therapy continues to be an important component of
      treatment of patients with advanced or recurrent endometrial cancer. Combination
      chemotherapy induces higher response rates in such patients. However, any
      advantage towards an improved survival remains a controversial issue.
      Isotretinoin plus interferon alfa-2a for squamous cell carcinoma of the cervix is
      still a topic of interest. There is a great need for agents and interventions
      with more efficacy and more specificity for the biology of the different
      gynecologic malignancies.

PMID- 8541393
TI  - Combined modality therapy for gynecologic cancer.
AB  - The use of combined modality therapy in the primary management of gynecologic
      cancer continues to be explored. Although early ovarian cancer is treated with
      postoperative adjuvant treatment, the data to support its value is lacking. In
      advanced disease, paclitaxel has emerged as the most optimal treatment after
      maximal cytoreduction. Although studies on consolidative therapy using
      radiotherapy, intraperitoneal therapy, or further chemotherapy are reported,
      there are no comparative data against a control arm. In those subsets of
      endometrial cancer patients who have a poor survival, adjuvant treatment
      strategies using chemotherapy or wide-field whole-abdominal therapy is being
      evaluated to improve outcome. Small phase II studies of either sequential or
      concurrent chemotherapy with radiation continue to be reported in advanced cervix
      cancer, yet large prospective randomized trials comparing standard radiotherapy
      to combined chemotherapy and radiotherapy are scarce. Alternative strategies to
      standard surgery to limit morbidity is being explored in the management of vulvar
      cancer with encouraging results. More properly conducted phase III trials are
      necessary to evaluate the efficacy of these newer treatment strategies.

PMID- 8541394
TI  - Advances in surgery for gynecologic malignancies.
AB  - Surgery has a significant role in the management of most gynecologic cancers.
      Recent developments in the diagnosis and management of ovarian, cervical,
      endometrial, and vulvar cancer are worthy of addressing in this review.
      Significant advances have occurred in the understanding of molecular genetic
      lesions, leading to a predisposition for ovarian cancer that may have a profound
      influence on prophylactic oophorectomy. Interval debulking surgery may provide a
      survival advantage for patients with advanced ovarian cancer. The loop
      electrosurgical excision procedure has become an integral part of the management
      of preinvasive disease of the cervix. Advances in the application of surgical
      stapling devices may lead to reduced operative time and blood loss for radical
      hysterectomy. Recent studies have addressed the adequacy of endometrial biopsy
      for the evaluation of postmenopausal bleeding. Advances in lymphatic mapping
      techniques have led to a novel application to the intraoperative identification
      of the sentinel node in vulvar cancer.

PMID- 8541396
TI  - Pattern of potassium ion and proton currents in the ovariole of the cockroach,
      Periplaneta americana, indicates future embryonic polarity.

PMID- 8541395
TI  - Biologic therapies for gynecologic cancer.
AB  - Recent advances in gynecologic tumor biology are discussed with an emphasis on
      the development of biologic therapy. Emerging knowledge regarding growth factors,
      regulatory cytokines, and cellular receptors offers new insight regarding tumor
      biology and the interaction of tumors with the host peritoneal cavity and immune
      system. Efforts to target ovarian cancer with antibodies directed against tumor
      associated antigens have begun to take advantage of molecular engineering
      techniques and have also explored an expanded panel of radionuclides with
      improved conjugation technology. It is hoped that these efforts will translate
      into successful strategies to improve the long-term survival of patients in
      conjunction with conventional chemotherapy.

PMID- 8541397
TI  - Chemotaxis, aggregation behavior, and foot formation in Dictyostelium discoideum
      amoeba controlled by microbeam uncaging of cyclic-AMP.

PMID- 8541398
TI  - Identification of calcium flux in single preimplantation mouse embryos with the
      calcium-sensitive vibrating probe.

PMID- 8541400
TI  - Reversible regression of cytokinesis induced by Ca2+ ionophore.

PMID- 8541399
TI  - Inhibitors of protein phosphatases (okadaic acid and tautomycin) block sea urchin
      development.

PMID- 8541401
TI  - Anaphase spindle dynamics under D2O-enhanced microtubule polymerization.

PMID- 8541402
TI  - Quantifying single and bundled microtubules with the polarized light microscope.

PMID- 8541403
TI  - Acetylcholine-induced Ca2+ flux across the sarcolemma of an echinoderm smooth
      muscle.

PMID- 8541405
TI  - Effects of exogenous heat shock protein (hsp70) on neuronal calcium flux.

PMID- 8541404
TI  - Retardation of the spread of extracellular Ca2+ into transected, unsealed squid
      giant axons.

PMID- 8541406
TI  - Regional differences in directional response properties of afferents along the
      saccule of the toadfish, Opsanus tau.

PMID- 8541407
TI  - Optical imaging of intrinsic signals from the Limulus optic nerve.

PMID- 8541408
TI  - Limulus is tuned into its visual environment.

PMID- 8541409
TI  - Flutter-like response in visual cortex of the semi-isolated turtle brain.

PMID- 8541410
TI  - The neurofilamentous network-smooth endoplasmic reticulum complex in transected
      squid giant axon.

PMID- 8541411
TI  - Fluorescent labeling of the glial sheath of giant nerve fibers.

PMID- 8541412
TI  - Effect of pH buffers on proton secretion from gastric oxyntic cells measured with
      vibrating ion-selective microelectrodes.

PMID- 8541413
TI  - Transmission of polarized light through sunfish double cones reveals minute
      optical anisotropies.

PMID- 8541415
TI  - Suppression of Ca2+ flux during the transition to anoxia in turtle hepatocytes
      revealed by a non-invasive Ca(2+)-selective vibrating probe.

PMID- 8541414
TI  - Dogfish (Mustelus canis) lens catalase reduces H2O2-induced opacification.

PMID- 8541416
TI  - Immunohistochemical localization of saxitoxin in the siphon epithelium of the
      butter clam, Saxidomus giganteus.

PMID- 8541417
TI  - Natural diets for Hermissenda crassicornis mariculture.

PMID- 8541418
TI  - Effects of land use on the degradability of dissolved organic matter in three
      watersheds of the Plum Island Sound estuary.

PMID- 8541419
TI  - Phylogenetic position of the dicyemid mesozoa inferred from 18S rDNA sequences.
AB  - The dicyemid mesozoa, obligate symbionts in the cephalopod kidney, are simply
      organized multicellular animals. They have long been the subject of phylogenetic
      debates. Some authors have suggested that dicyemids represent an offshoot from an
      early metazoan ancestor. Other workers considered them to be degenerated progeny
      of higher metazoa, possibly parasitic trematodes. We determined the almost
      complete nucleotide sequences of 18S rDNA in two species of dicyemid, Dicyema
      orientale and Dicyema acuticephalum, isolated purely from cephalopod urine. We
      compared these sequences with sequences determined in the present study from
      three flatworm species, as well as with a variety of eukaryote sequences obtained
      from databases. The phylogenetic trees reconstructed with the use of the neighbor
      joining, maximum-parsimony, and maximum-likelihood methods indicated that the
      dicyemids belong among the triploblastic animals (Bilateria). However, we cannot
      firmly establish the position of the dicyemids within the Bilateria because we
      cannot ignore the problem of long branch attraction between the myxozoans,
      dicyemids, nematodes, and acoel flatworms. The present results favor the
      hypothesis that the dicyemids do not represent an early divergent metazoan group,
      but rather a group degenerated from a triploblastic ancestor.

PMID- 8541420
TI  - Diagnosis and treatment of constipation.

PMID- 8541421
TI  - Effects of naloxone on glucagon and insulin concentrations after injection of
      endotoxin in rats.
AB  - OBJECTIVE: To find out how infusions of endotoxin and endotoxin plus naloxone
      affected glucose, glucagon, and insulin concentrations in rats. DESIGN: Random
      control study. SETTING: University hospital, Norway. MATERIAL: 27 Male Wistar
      rats. INTERVENTIONS: 8 Rats were given Escherichia coli endotoxin 0.25 mg in
      saline; 5 were given a naloxone infusion (0.4 ml of 0.04 mg/ml for the first half
      hour and continued at a rate of 0.4 ml/hour for a total of 80 minutes) starting
      10 minutes before the same dose of endotoxin; 6 were given saline alone for 70
      minutes, and 8 saline alone for 10 minutes. Blood was taken for analysis after 70
      minutes in the first three groups and at the end of the infusion in the 10 minute
      group. MAIN OUTCOME MEASURES: Serum concentrations of glucose, glucagon, and
      insulin compared with baseline (10 min group). RESULTS: Median (interquartile)
      concentrations of all three substances rose significantly 70 minutes after the
      injection of endotoxin compared to basal values: 9.8 (8.2-10.9) compared with 6.0
      (4.8-7.5) mmol/l for glucose (p < 0.01); 53.1 (44.6-56.0) compared with 3.6 (3.1
      5.1) ng/l for glucagon; and 39.4 (38-50.4) compared with 16.7 (11.2-25.5) pmol/l
      for insulin. When naloxone was combined with endotoxin glucagon and insulin
      concentrations were significantly lower: 24.3 (23.9-37.5) ng/l (p < 0.01), and
      30.6 (24.5-31.6 pmol/l (p < 0.05), respectively. The concentration of glucose in
      venous blood was unchanged. CONCLUSIONS: The rise in glucagon and insulin
      concentrations after endotoxin infusions may be partly mediated by opioids.
      Naloxone in the dose given did not abolish the increase in glucagon after
      endotoxin. The high glucagon:insulin ratio after both endotoxin alone and
      endotoxin plus naloxone may be important in the aetiology of the hyperglycaemia
      seen.

PMID- 8541422
TI  - Metabolic effects of two regimens of growth hormone given before operation in
      piglets.
AB  - OBJECTIVE: To clarify the effects of growth hormone (GH) given three days before
      and at the start of a standard abdominal operation or at the start of the
      abdominal operation alone in piglets. DESIGN: Randomised experiment. SETTING:
      University hospital, Norway SUBJECTS: Twenty-four piglets. INTERVENTIONS: GH 24
      IU was given intramuscularly for either three days before and on the morning of
      the operation or on the morning of a standard abdominal operation only (n = 8 in
      each group) A further 8 piglets acted as untreated controls. MAIN OUTCOME
      MEASURES: Diameter of fibres in the soleus and gastrocnemius muscles; urinary
      nitrogen excretion; and fat and carbohydrate oxidation measured by indirect
      calorimetry. RESULTS: Nitrogen excretion was reduced (in the three days group the
      mean (SEM) was 30.8 (4.2) mg/kg, corresponding figures from the one day group and
      the controls were 37.6 (5.8) and 55.4 (3.1) mg/kg, respectively, p = 0.004). Fat
      oxidation increased (for the whole period: p = 0.014) and carbohydrate oxidation
      decreased (p = 0.02) in the one day group only. The diameter of type I muscle
      fibres was increased in both muscles (soleus, three day group, mean (SEM)
      37.5(1.4) microns compared with control, 30.4(0.6) microns, p = 0.001, and
      gastrocnemius, three day group 38.6(1.3) microns compared with control, 30.8(1.4)
      microns, p = 0.01). CONCLUSIONS: Three days treatment with GH enhanced nitrogen
      sparing and attenuated changes in fat and carbohydrate oxidation induced by one
      day treatment, but induced hypertrophy of type I muscle fibres.

PMID- 8541423
TI  - Effects of peritonitis exudates on chemotaxis and phagocytosis of human
      neutrophils.
AB  - OBJECTIVE: To elucidate the in vitro effects of peritoneal exudate in patients
      with peritonitis on the functions of normal neutrophils (chemotaxis and
      phagocytosis) and to correlate these findings with constituents of the exudate,
      severity of disease, and clinical course. DESIGN: Open study. SETTING: University
      hospital, Germany. SUBJECTS: Fifty consecutive patients with secondary
      peritonitis and healthy volunteers. INTERVENTIONS: Samples of peritoneal exudate
      were taken during operation and tested for their ability to stimulate or inhibit
      chemotaxis and phagocytosis of polymorphonuclear neutrophils (PMN). MAIN OUTCOME
      MEASURES: Correlation between chemotaxis and phagocytosis and concentrations of
      constituents of peritoneal exudate. RESULTS: Mean (SD) exudate-induced chemotaxis
      was 102.5 (22.8) microns compared with 62.3 (4) in the buffer control and 116
      (17) in the 1 ng/ml C5a buffer control. The mean (SD) phagocytic index (uptake of
      zymosan and Candida albicans) was 68.8 (28.1) % of the respective serum control.
      There were correlations between chemotaxis and concentrations of C3a, endotoxin,
      and white cell count in the exudates; between phagocytosis and concentrations of
      C3a, IgG, IgM, protein and granulocyte elastase activity (GE and GE-alpha 1
      proteinase inhibitor complex) in the peritoneal exudate; concentrations of
      endotoxin, and tumour necrosis factor alpha (TNF alpha), and granulocyte elastase
      activity in the exudate; and concentrations of C3a, IgG, IgM, and fibrinopeptide
      A in the exudate. There were no differences in chemotaxis and phagocytosis
      between patients who survived and those who died, and only the APACHE II score,
      the Sepsis Severity Score and the Mannheim Peritonitis Index correlated with
      mortality. CONCLUSION: It is still not clear whether other constituents of the
      exudate, variable conditions of resorption, inflammatory conditions within the
      peritoneal lining, or the individual patient's capacity to limit the systemic
      response, may have a critical role.

PMID- 8541424
TI  - Mechanical factors influencing the incidence of burst abdomen.
AB  - OBJECTIVE: To compare laparotomy closure with interrupted polyglactin 910
      (Vicryl) and continuous polydioxanone (PDS II), and assess the mechanical and
      other factors that influenced the incidence of burst abdomen. DESIGN:
      Retrospective study. SETTING: University hospital, The Netherlands. SUBJECTS: A
      random sample of 346 patients who did not burst their abdomens, taken from the
      total of 3768 patients who underwent primary midline laparotomy from 1986-1990,
      together with the 45 (1%) from the total series who did burst their abdomens.
      MAIN OUTCOME MEASURES: Incidence of burst abdomen, and the association with
      mechanical and others risk factors. RESULTS: There were no differences in the
      incidence of burst abdomen between those sutured with interrupted polyglactin 910
      and those sutured with continuous polydioxanone (p = 0.12). Layered closure
      resulted in significantly more burst abdomens than any other method of closure (p
      < 0.001 in each case). Postoperative wound infection (14/43, 33%, compared with
      33/343 10%) and pulmonary complications (25/43, 58%, compared with 44/344, 13%)
      were also significantly associated with the development of burst abdomens (p <
      0.001). CONCLUSIONS: A continuous, monofilament, absorbable suture should be used
      to close a laparotomy incision. Elastic suture material, loop sutures, an the
      continuous figure-of-eight technique should be investigated.

PMID- 8541425
TI  - Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal
      surgery. Multicentre trials 20 mg and 40 mg enoxaparin versus dextran.
AB  - OBJECTIVE: To compare enoxaparin and dextran 70 for the prophylaxis of
      venographically diagnosed deep vein thrombosis (DVT) after gastrointestinal
      operations. DESIGN: Part 1: randomised double blind trial; Part 2: single blind
      study with historical controls. SETTING: Eight Norwegian hospitals. SUBJECTS: 381
      Patients undergoing elective gastrointestinal operations. INTERVENTIONS: Part 1
      (n = 329): enoxaparin 20 mg subcutaneously starting two hours before operation
      and continuing until the patient was fully mobilised or had had 10 injections and
      a placebo infusion of 0.9% sodium chloride, or dextran 70,500 ml at the start of
      the operation, on the evening of operation, and on the first, third, and fifth
      postoperative days and placebo subcutaneous injections. Part 2 (n = 52):
      enoxaparin 40 mg in the same regimen as part 1 (compared with 39 historical
      controls). Venograms 4-6 days post-operatively. MAIN OUTCOME MEASURE:
      Venographically confirmed DVT. RESULTS: Part 1: Because of the high overall
      incidence of DVT an interim analysis was done which showed 33/101 DVT (33%) among
      high risk patients in the enoxaparin 20 mg group and 33/107 (31%) in the dextran
      70 group. The corresponding figures for patients at medium risk were 2/27 (7%)
      for enoxaparin 20 mg and 5/27 (19%) for dextran 70 (95% confidence interval (CI)
      for the difference--11.9 to 9.8). Part 2: the dose of enoxaparin was therefore
      increased to 40 mg and prophylaxis restricted to patients with cancer. There were
      6/49 DVT (12%), which was compared with a random sample from the dextran 70 group
      from part 1 (historical controls) in which the incidence was 15/39 (38%, 95% CI
      of the difference 4.0 to 8.4). There were no pulmonary emboli, only 4 thrombi
      were above the knee and there were 4, 1 and 3 clinical DVT in the 20 mg and 40 mg
      enoxaparin, and dextran 70 groups, respectively. CONCLUSIONS: Enoxaparin 20 mg
      and dextran 70 are effective prophylaxis for patients at medium risk, but
      enoxaparin 40 mg is required for those at high risk.

PMID- 8541426
TI  - Morbidity, ability to swallow, and survival, after oesophagectomy for cancer of
      the oesophagus and cardia.
AB  - OBJECTIVE: To study survival, morbidity, and ability to swallow, after
      oesophagectomy for cancer of the oesophagus and cardia. DESIGN: Prospective open
      study. SETTING: University hospital, Norway. SUBJECTS: 83 patients, 38 with
      squamous cell carcinoma and 45 with adenocarcinoma of the oesophagus and cardia.
      INTERVENTIONS: Transhiatal (n = 51) and transthoracic (n = 32) oesophagectomy.
      Oesophageal replacement was by either stomach (n = 80) or colon (n = 3). Cervical
      anastomosis was used in all but 2. MAIN OUTCOME MEASURES: Early and late
      morbidity and mortality, length of stay in intensive care unit and in hospital,
      and survival analysis. RESULTS: 30 Day and in hospital mortality were 0 and 4%
      for transhiatal, and 6% and 9% for transthoracic, oesophagectomy. Complications
      included recurrent nerve palsy (n = 7), anastomotic leaks (n = 5), and
      chylothorax (n = 4). 17 Patients (22%) needed dilatations for stenosis of the
      anastomosis, and 71 (85%) of the patients left hospital within four weeks of
      operation. Survival analysis showed a 5 year survival rate of 33% for patients
      with adenocarcinoma operated on for cure and a 2 year survival of 28% for
      patients with squamous cell carcinoma. CONCLUSIONS: Oesophagectomy for cure is
      worthwhile as some patients are cured and most of the remainder have prolonged
      relief of their dysphagia. Palliative resections should not be done in patients
      with distant metastases or invasion of adjacent organs by the tumour because of
      long stay in hospital, appreciable morbidity, and short life expectancy.

PMID- 8541427
TI  - Liver segmentectomy as anatomically precise resections. An experimental study in
      sheep.
AB  - OBJECTIVE: To assess a new technique of anatomically precise hepatic segmental
      resection and to compare the degree of precision and biochemical profiles with
      results after traditional segmental resection and a sham operation. DESIGN:
      Experimental study. SETTING: University hospital, Germany. MATERIAL: 50 sheep (10
      each had segments II, III, and IV removed by the new technique, and 10 each were
      studied in the traditional resection and sham operated groups). INTERVENTIONS:
      Operative ultrasonography and injection of methylene blue to identify segmental
      boundaries. In traditional operations boundaries were identified only from
      knowledge of the surface structure of the liver. MAIN OUTCOME MEASURES: Degree of
      precision, duration of operation, blood loss, mortality, transaminase activities
      and liver function tests. RESULTS: Anatomically precise segmentectomies were
      achieved in 6/9 (67%) for segment II, 6/9 (67%) for segment III, and 4/8 (50%)
      for segment IV. Using the traditional technique (segment III only) there was only
      1/10 anatomically precise resections, together with 5 perisegmentectomies and 4
      incomplete resections (p < 0.02). The operations for anatomically precise
      resection lasted significantly longer, but resection time was similar. Blood
      loss, survival, and transaminase activities were similar for the two groups, but
      the margin of necrosis at the cut edge was significantly less in anatomically
      precise resections. CONCLUSION: Anatomically precise hepatic resections are
      technically feasible with the use of intraoperative ultrasonography and selective
      staining of the segment(s) to be removed with methylene blue. Although it takes
      longer, there are no detrimental consequences compared with the considerably less
      accurate traditional technique.

PMID- 8541428
TI  - Hepatodochojejunostomy Roux-en-Y by mucosal graft with a transanastomotic tube.
      Surgical technique.

PMID- 8541429
TI  - Spontaneous subcapsular rupture of hepatic haemangioma.

PMID- 8541430
TI  - Giant condyloma acuminatum (Buschke-Loewenstein tumour) of the anorectum with
      malignant transformation.

PMID- 8541431
TI  - Internal hernia of foramen of Winslow: a rare congenital condition.

PMID- 8541432
TI  - Emphysema of the right thigh secondary to strangulated crural hernia (Richter's
      hernia).

PMID- 8541433
TI  - [Antagonists in anesthesia].
AB  - In modern anaesthesia various antagonists are used. They provide efficient tools
      to facilitate better control of pharmacological effects and side effects of drugs
      routinely used in anaesthesia. Naloxone is a competitive antagonist of opioids
      without any intrinsic activity. It counteracts respiratory depression, pruritus,
      sedation and analgesia caused by opioids. It is fast-acting with a duration of
      action of 45 to 90 min. Several investigators have reported severe side effects
      of naloxone including hypertension, tachyarrhythmias, left heart failure and
      cardiac arrest, and hence the use of naloxone must be carefully considered in
      every single patient. Flumazenil is a competitive antagonist of benzodiazepines.
      It is a remarkably safe drug and very effective to terminate all benzodiazepine
      effects in anaesthesia and intensive-care patients. Serious complications caused
      by flumazenil have been reported in patients receiving benzodiazepines in the
      treatment of seizure disorders and in patients with mixed intoxications.
      Neostigmine is one of several antagonists of neuromuscular blocking agents. Its
      side effects include bradycardia, increased bronchial secretions and increased
      peristalsis. Indication depends on the results of neuromuscular monitoring.
      Physostigmine is an unspecific antagonist of the central anticholinergic
      syndrome, an acute psychosis that may be caused by numerous drugs used in
      anaesthesia. Generally, antagonists should be carefully titrated. In emergency
      medicine the use of these antagonists is not recommended; the primary goal is to
      restore vital functions.

PMID- 8541434
TI  - [Clinical potency of nitrous oxide--is MAC the gold standard?].
AB  - Nitrous oxide is delivered during most cases of general anaesthesia. Though it
      has a history of approx. 150 years there is no univocal understanding about its
      clinical potency. Research studies during the last 10 years support, however, the
      view that 1. the potency of nitrous oxide in the clinical settings is only 1/3 of
      the potency as estimated from the MAC value; 2. the potency of combinations of
      nitrous oxide and volatile anaesthetics is represented more appropriately by
      quantities which are derived from the EEG than by the addition of MAC fractions.
      The findings of the last 10 years do not support the hypothesis, that the
      addition of nitrous oxide to the breathing gas is more beneficial than waiving
      the use of nitrous oxide.

PMID- 8541435
TI  - [Quantitative assessment of catecholamine secretion as a rational principle of
      anesthesia management in pheochromocytoma surgery].
AB  - AIM OF THE STUDY: Fifteen patients with phaeochromocytoma who underwent surgery
      were studied consecutively. METHODS: They received either (10) a balanced
      anaesthesia technique with isoflurane and fentanyl or (5) a combination of
      propofol and alfentanil for total intravenous anaesthesia. EEG processing was
      performed in order to guarantee adequate anaesthetic depth. Antihypertensive
      therapy was performed with sodium nitropusside. Continuous blood sampling was
      performed with a roller pump and an autosampler system in order to get high
      resolution measured of plasma catecholamines. Their concentration was measured by
      HPLC with electrochemical detection. RESULTS: There were 100fold differences in
      the maximal catecholamine concentrations during phaeochromocytoma resection
      between patients. In some cases adrenaline and noradrenaline levels exceeded
      normal values by a factor of 1000 to 1500. Secretion rates were calculated on a
      pharmacokinetic basis an revealed secretion rates of 0.3 to 97.3 micrograms/min
      for adrenalin and 6.7 und 402.8 micrograms/min for noradrenaline. If systolic
      blood pressures were greater than 160 mmHg sodium nitroprusside was given by
      infusion with a rate of 300 +/- 315 micrograms/min. Over a period of 69.2 +/-
      39.8 min during resection of the tumor the total dose was 7017 +/- 12433
      micrograms. CONCLUSIONS: There were positive correlations between plasma
      catecholamine concentrations, systolic blood pressure values, and infusion rates
      of sodium nitroprusside. The comparison of the two anaesthetic techniques
      resulted in a significant reduction of antihypertensive therapy and more stable
      haemodynamics in patients with total intravenous anaesthesia. However, the
      beneficial effect of this anaesthesia regimen has to be proven on a larger basis
      of patients in a randomized manner.

PMID- 8541436
TI  - [Which dosage concept for adrenaline is correct in cardiopulmonary resuscitation?
      A data analysis of preclinical resuscitations].
AB  - AIM: Epinephrine is the drug of choice in cardiopulmonary resuscitation. Its
      dosage, however, is controversially discussed. The American Heart Association
      recommends for standard use in adults 1 mg epinephrine every 3-5 minutes, but
      classifies a medium dose, a high dose and a step-by-step escalating dosage
      concept as potentially useful alternatives. Aim of this study was to develop a
      rationale for the escalating dosage concept using an analysis of preclinical
      resuscitation data. METHODS: Bonn city (141 km2, 310,000 residents, 52% female,
      13.9% > 65 years) was served by a double-response system of two ALS-units
      (staffed by physicians) and four BLS-units (staffed by paramedics). All patients
      were included in this data analysis, which were cardiopulmonary resuscitated
      according to the AHA guidelines by the ALS-unit Bonn-North (66% of area and
      240,000 residents) from 1989 to 1994. All relevant data were documented by the
      emergency physicians using preformed treatment sheets. Discharge rates were
      determined by reviewing the hospital records, and one-year survival data were
      collected by mail contact with the primary physicians. The correlations between
      duration of cardiac arrest, dosage of epinephrine and outcome were determined by
      regression analysis in patients older than 17 years suffering from unwitnessed
      and bystander-witnessed cardiac arrest. Statistical significance was assumed for
      p < 0.05. RESULTS: Within 1989 to 1994 the ALS-team of Bonn-North resuscitated
      685 cardiac arrest patients with presumed cardiac aetiology in 383 (56%) return
      of spontaneous circulation (ROSC) could be achieved. The epinephrine dosage
      required to achieve ROSC increased with prolongation of cardiac arrest interval
      (1989-1994; patients with ROSC selected, n = 263; r = 0.2276; p = 0.0002).
      Resuscitation success, however, decreased with increasing, dosage of epinephrine
      (1989-1992; n = 345; ROSC: r = -0.2643; p < 0.001; survival > 24 h: r = -0.3393;
      p < 0.001; discharge: r = -0.1677; p = 0.0018; survival > 1 year: r = -0.2685; p
      < 0.001). CONCLUSION: Based on these data, we recommend an escalating epinephrine
      dosage concept, which facilitates titration of the drug to an effective level and
      meets the needs of the individual patient. This concept avoids overdosage in
      patients who had just collapsed shortly before initiation of CPR, attains higher
      levels of epinephrine in patients suffering from prolonged cardiac arrest, and
      takes into consideration that the effective epinephrine dose varies individually
      and increases with prolongation of the cardiac arrest interval.

PMID- 8541437
TI  - [Clonidine increases the anesthetic effectiveness of thiopental].
AB  - OBJECTIVE: Treatment with alpha 2-agonists has been demonstrated to improve intra
      and postoperative haemodynamic stability. After administration of alpha 2
      agonists anaesthetic requirements have been shown to be reduced up to 90% for
      volatile anaesthetics as well as for intravenous anaesthetics like barbiturates.
      This study was designed to determine the effect of the alpha 2-agonist clonidine
      on the anaesthetic potency of the intravenous anaesthetic thiopental in absence
      of pharmacokinetic influences. METHODS: With approval by the local animal care
      committee all experiments were performed using Xenopus laevis tadpoles in the
      early pre-limb-bud stage. The animals were exposed to thiopental (0.1-250 microM)
      or a combination of thiopental (0.1-250 microM) + clonidine (100 microM) for up
      to 120 min. For each concentration at least ten animals were used. Anaesthesia
      was defined as loss of righting reflex for 10 s. Based on the response of the
      tadpoles at different concentrations of the anaesthetic a concentration-response
      curve was generated according to a method for quantal biologic data and
      halfmaximal concentrations (EC50) as well as slopes of the curves were
      calculated. All values are reported as mean +/- sem. Statistical significance was
      determined by Student's t-test (p < 0.05). RESULTS: The fraction of anaesthetised
      animals increased with increasing concentrations of thiopental. The logistic
      concentration-response plots showed a sigmoidal curve with a slope of 2.14 +/-
      0.3. Calculation of the EC50 resulted in a value of 25.5 +/- 2.0 microM. In
      presence of clonidine thiopental exhibited a left shift of the concentration
      response curve with an EC50 of 12.3 +/- 1.6 microM (Slope: 2.75 +/- 0.3).
      CONCLUSION: The presented data confirm the clinical impression that clonidine
      exercises an anaesthetic sparing effect. Clonidine enhances the anaesthetic
      potency of thiopental under equilibrium conditions, thus allowing to exclude
      pharmacokinetic influences as well as excluding effects of adjuvants. It is
      concluded that the reduction of requirement of anaesthetics by clonidine is due
      to a pharmacodynamic effect.

PMID- 8541438
TI  - [Effect of premedication and barbiturate hypnotics on motor evoked potentials
      induced by magnetic cortex stimulation].
AB  - OBJECTIVE: The aim of this study was to investigate the influence of the
      premedication and the influence of the two barbiturates methohexital and
      thiopental on magnetically evoked compound muscle action potentials (magnet MEP)
      in humans. METHODS: 40 Patients (ASA-PS I-II) undergoing lumbar nucleotomy were
      included in this study after obtaining written informed consent. The study was
      approved by the local ethical committee. All patients were premedicated with 0.5
      mg atropine, 25 mg promethazine and 50 mg pethidine. For induction of anaesthesia
      patients randomly received methohexital or thiopental by continuous infusion with
      increasing infusion rates every 15 seconds up to a minimal anaesthesia level in
      15 minutes. Transcranial magnetic stimulation was delivered by the magstim 200
      magnetic stimulator. Magnetic MEPs were recorded from the surface of the short
      abductor pollices muscle. MEP-examination was performed preoperatively, after
      premedication and every two minutes during the induction of anaesthesia. Every
      other two minutes the patients level of consciousness were assessed and
      documented. Statistical calculations were performed with the U-test. RESULTS: No
      statistical differences were found for the mean induction time in the two groups.
      No statistical difference in amplitude and latency could be observed between the
      preoperative values and the values measured after premedication. During
      anaesthesia induction the amplitude decreased in both groups. In 25 of the 40
      cases, the MEP disappeared completely before the patients fell asleep. The
      thiopental group showed a significantly lower incidence of MEP preservation (20%)
      compared to methohexital (50%). CONCLUSIONS: Premedication with atropine,
      promethazine and pethidine has no influence on magnetic MEP. Methohexital allows
      the highest incidence of successful MEP recordings with sufficient anaesthesia. A
      success rate of only 50% even in cases without motorpathway affection makes the
      application of magnetic MEP an unreliable tool for intraoperative monitoring.

PMID- 8541439
TI  - [Objective quantification of spinal anesthesia by somatosensory evoked potentials
      after tibial nerve stimulation].
AB  - Eight patients (ASA status I) who had to undergo minor surgery of the knee
      received spinal anaesthesia by 80 mg hyperbaric mepivacaine. Clinical parameters
      of the block were compared with somatosensory evoked potentials (SEP) after
      tibial nerve stimulation. Depending on the degree of nervous block, the early
      components P40, N50 and P60 of the cortical tibial SEP underwent characteristic
      changes. After the injection of the local anesthetic, the latencies of the early
      components rapidly increased. The tibial SEP completely disappeared after 15 min
      (median). At this time pin prick testing revealed a complete somatosensory block
      in the corresponding dermatomes. With one exception, motor block was also
      complete. After 115 min (median) the early components could be recorded again,
      with latencies significantly increased. The maximum latency shifts were 22.2%
      (P40), 19.6% (N50), and 11.8% (P60). When the latencies recovered to less than
      10% of the starting value, anaesthesia became clinically insufficient. The
      recovery of the afferent pathway was complete within 5 hours. Because of the good
      correspondence with the clinical blockade, the latency shift of P40, N50 and P60
      is useful in objectively evaluating a spinal anesthesia with mepivacaine. The use
      of the method is limited by increased equipment and staffing requirements;
      however, it facilitates the development of optimised dosing strategies.

PMID- 8541440
TI  - [Enflurane blocks ion current through the nicotinic acetylcholine receptor].
AB  - AIM: The study investigates the influence of enflurane (EN) on macroscopic
      currents of the nicotinic acetylcholinergic receptor channel (nAChR). This ion
      channel is a representative member of the superfamily of ligand-gated receptor
      channels and is better characterized than all the other receptors in respect of
      structure and function. METHODS: For the experiments the patch-clamp technique
      was used to study the embryonic type of the nAChR expressed by cultured mouse
      myotubes. Patch-clamp recordings were performed in the outside-out-mode from
      these preparations. To match the rapid desensitization kinetics of ligand
      activated ion channels, a liquid filament switch technique was used for the
      application of agonists to the excised patches. This technique allows for change
      of solution within 300 microseconds. We used a saturating concentration of 10(-4)
      M acetylcholine (ACh), activating almost all available ion channels on a patch.
      Pulses of 10(-4) M ACh together with EN in different concentrations were applied
      repetitively. RESULTS: The current elicited by 10(-4) M ACh is reduced reversibly
      in a concentration-dependent manner by EN in clinically relevant concentrations:
      1,44 x 10(-5) M EN inhibit about 10%, 1.44 x 10(-4) M 25%, 1.44 x 10(-3) M 35%,
      and 1.44 x 10(-2) M 75% of the ion flux (averaged results from 48 patches). EN
      decreases the time constant of the current decay. This acceleration of
      desensitisation kinetics is partly reversible if followed by application of 10(
      4) M ACh. CONCLUSION: In this study we were able to show that EN reduces the
      currents of the ligand-gated embryonic-like nAChR in clinically relevant
      concentrations. Volatile anaesthetics are known to influence GABAA-, glutamate-,
      and glycine- activated receptors, which are members of the same family of ligand
      gated receptor-channel units. Thus, the action of volatile anaesthetics on ligand
      gated receptors may play a role in the mechanism of general anaesthesia. The
      interaction of volatile anaesthetics with nondepolarising neuromuscular blockers
      may also be based on this effect at the neuromuscular junction.

PMID- 8541441
TI  - [Do general anesthetics act on specific receptors?].
AB  - First of all, the meanings of the terms anaesthesia, anaesthetic and receptor are
      defined. Examples of anaesthetic actions in model systems are then described and
      compared with clinical actions of anaesthetics. When anaesthetics achieve a
      certain membrane concentration, they begin to influence membrane protein function
      in a nonspecific manner. If the anaesthetic drug possesses polar functional
      groups in addition to lipophilic ones, it may selectively affect membrane
      proteins and interact with them specifically. The absolute lipophilicity of a
      drug does not necessarily determine whether or not a drug is a suitable
      anaesthetic. Rather, it is important that the drug does not show undesirable side
      effects when it achieves a critical membrane concentration at which lipophilic
      interactions occur. There are examples of specific interactions of general
      anaesthetics with receptors as well as examples of nonspecific effects on
      membranes. Whether these interactions are important for anaesthesia remains to be
      seen.

PMID- 8541442
TI  - [Intravenous anesthesia with inhalation anesthetics].
AB  - The authors describe intravenous anaesthesia with diethyl ether that has been in
      use for over 70 years as the only clinically useful form of anaesthesia with
      intravenously applied volatile anaesthetics. Intravenous ether anaesthesia, which
      had been introduced in 1909 by Burkhardt, was rarely but regularly used in Europe
      and the United States between 1910 and 1930. In the course of development of new
      intravenous anaesthetics such as hexobarbital and thiopental, which were easier
      to handle, intravenous ether narcosis was used only sporadically after 1930. The
      method, however, has certain "pros", such as: rapid and excitation-free
      introduction, good manageability, only mild postnarcotic disturbances and volume
      substitution by the carrier solution. The "cons" are a quite considerable
      incidence of venous irritations and thromboses, complicated and costly equipment
      and preparation of the solution as well as cardiovascular stress in case of
      cardiac insufficiency patients. Simulation confirmed the statements from
      literature in respect of the characteristic features concerning induction and
      manageability.

PMID- 8541443
TI  - Conformational characteristics of peptides containing alpha, beta-dehydroamino
      acid residues.
AB  - The structural preferences of synthetic peptides containing alpha, beta
      dehydroamino acid residues, as determined by theoretical studies, x-ray
      diffraction analyses, and spectroscopic studies, are reviewed. The role of delta
      ZPhe residues in stabilizing type II beta-turn structures in small peptides and
      in nucleating helical structure in longer peptides is exemplified by several
      crystal as well as solution structural studies. From the few studies reported so
      far it appears that delta ZLeu influences the peptide backbone, much like the
      delta ZPhe residue, whereas delta Ala prefers the extended conformation,
      suggesting that the nature of beta substituents might influence the conformation
      restriction behavior of the dehydroresidues. Conformational studies on synthetic
      peptides containing delta E, delta ZAbu, and delta Val have also been described.

PMID- 8541444
TI  - Structural studies of opioid peptides: a review of recent progress in x-ray
      diffraction studies.
AB  - The solid state structures of many opioid peptide agonists have been elucidated
      by x-ray diffraction analysis. Recently, the first structure of an opioid peptide
      antagonist has been determined. Theoretically, linear peptides can have many
      different backbone conformations, yet early x-ray studies (1983-1987) on
      enkephalin and its analogues showed only two different backbone conformations:
      extended and single beta-bend. In 1989 enkephalin was observed in a third
      conformation, a double beta-bend. Since that time diffraction studies have been
      completed on the rationally designed linear opioid peptide agonists DTLET (Tyr-D
      Thr-Gly-Phe-Leu-Thr) and DADLE (D-Ala2,D-Leu5-enkephalin) as well as on several
      cyclic enkephalin analogues including DPDPE (Tyr-[D-Pen-Gly-Phe-D-Pen]) and JOM
      13 (Tyr-[D-Cys-Phe-D-Pen]). The most recent review of the x-ray studies on this
      class of compounds was written in 1988. This paper will update that review to
      include the results of studies completed since that time.

PMID- 8541445
TI  - Molecular structure and mechanisms of action of cyclic and linear ion transport
      antibiotics.
AB  - Ionophores are antibiotics that induce ion transport across natural and
      artificial membranes. The specific function of a given ionophore depends upon its
      selectivity and the kinetics of ion capture, transport, and release. Systematic
      studies of complexed and uncomplexed forms of linear and cyclic ionophores
      provide insight into molecular mechanisms of ion capture and release and the
      basis for ion selectivity. The cyclic dodecadepsipeptide valinomycin, cyclo[(-L
      Val-D-Hyi-D-Val-L-Lac)3-], transports potassium ions across cellular membrane
      bilayers selectively. The x-ray crystallographic and nmr spectroscopic data
      concerning the structures of Na+, K+, and Ba+2 complexes are consistent and
      provide a rationale for the K+ selectivity of valinomycin. Three significantly
      different conformations of valinomycin are observed in anhydrous crystals, in
      hydrated crystals grown from dimethylsulfoxide, and in crystals grown from
      dioxane. Each of these conformations suggests a different mechanism of ion
      capture. One of the observed conformations has an elliptical structure stabilized
      by four 4<--1 intramolecular hydrogen bonds and two 5<--1 hydrogen bonds. Ion
      capture could be readily achieved by disruption of the 5<--1 hydrogen bonds to
      permit coordination to a potassium ion entering the cavity. The conformation
      found in crystals obtained from dimethyl sulfoxide is an open flower shape having
      three petals and three 4<--1 hydrogen bonds. Complexation could proceed by a
      closing up of the three petals of the flower around the desolvating ion. In the
      third form, water molecules reside in the central cavity of a bracelet structure
      having six 4<--1 hydrogen bonds. Two of these bracelets stack over one another
      with their valine-rich faces surrounding a dioxane molecule. The stacked
      molecules form a channel approximately 20 A in length, suggesting that under
      certain circumstances valinomycin might function as a channel. A series of
      analogues of valinomycin differing in ring composition and size have been
      synthesized and their transport properties tested. Peptide substitution and
      chiral variation in the dodecadepsipeptide can result in stabilization or
      modification of the different conformers. While contraction of the ring size
      results in loss of ion transport properties, expansion of the ring size permits
      complexation of larger ions and small positively charged molecules. Gramicidin A
      is a pentadecapeptide that functions as a transmembrane channel for transporting
      monovalent cations. Crystal structures of the cesium chloride complex and two
      uncomplexed forms of gramicidin A have been reported. In all three structures the
      gramicidin A molecule is a left-handed, antiparallel, double-stranded helical
      dimer. In the cesium complex the beta 7.2-helix has 6.4 residues per turn with an
      internal cavity large enough to accommodate cesium ions. In the uncomplexed
      structures the channel is 31 A long and has 5.6 amino acids per turn. Because the
      helix is too tightly wound to permit ion transport, ion transport would require
      breaking and reforming of hydrogen bonds.

PMID- 8541446
TI  - Flexibility in peptide molecules and restraints imposed by hydrogen bonds, the
      Aib residue, and core inserts.
AB  - The first segments of this article review some of the early crystal structure
      determinations of beta-bends, gamma-bends, large conformational changes in cyclic
      peptides upon complexation with metal ions, and both the stability and drastic
      change in conformation as a function of the solvent used for growing crystals.
      More recent structure analyses have concerned helical peptides containing the Aib
      and/or Dpg residues and associated conformational problems such as 310-/alpha
      helix transitions, helix aberrations, reversals, severe curving of the helix,
      unfolding, and hydration of backbone. Ion channels occurring in three crystal
      forms of zervamicin and possible ion transport and gating mechanisms are
      described. Finally, hydrogen bonding patterns are presented in supramolecular
      assemblies of retropeptides with core inserts consisting of oxalyl, adipoyl,
      suberoyl and polymethylene moieties.

PMID- 8541447
TI  - X-ray crystallography of peptides: the contributions of the Italian laboratories.
AB  - The review article summarizes the most relevant solid state structural and
      conformational results obtained in the laboratories involved in Italy in the
      studies of synthetic and natural peptides by x-ray diffraction analyses. Some of
      the topics will include research studies carried out in other European countries,
      whereas in other cases studies carried out in Italy will be included in other
      review articles included in this volume. The review deals with peptides
      containing symmetrically achiral and unsymmetrically chiral C alpha,alpha
      dialkylated glycine residues, peptides containing beta-alanine residues,
      alpha,beta-dehydroamino acid residues, and aminosuccinyl residues, peptides
      containing the thioamide surrogate, heterochiral peptides and several bioactive
      peptides systems with the proposed relationships between function and structure.

PMID- 8541448
TI  - Crystal structures of peptides and modified peptides.
AB  - The X-ray diffraction experiments on peptides and related molecules which have
      been carried out in Western Europe, except Italy, in the last eight years are
      reviewed. The crystal structures of some bioactive peptides such as Leu
      enkephalin (a neurotransmitter), cyclosporin A (an immunomodulator in both the
      free and protein-bound state), balhimycin (an antibiotic) and octreotide (a
      somatostatin analogue) are briefly presented. Crystallized N- and C-protected
      model peptides have given an insight into the folding tendency and folding modes
      depending on the peptide sequences. The crystal structures of various
      pseudopeptide molecules reveal how the three-dimensional structure of peptide
      analogues can be modulated by substituting non-peptide groups for the peptide
      bond. A few examples of structural mimetics of the beta- and gamma-turns, and of
      templates for alpha-helix induction are also presented.

PMID- 8541449
TI  - Recent structural studies of peptides in Japan.
AB  - Recent x-ray structure analyses of peptides in Japan were reviewed. A series of
      peptides containing an aminoisobutyric acid (Aib) residue was analyzed and their
      helical types were investigated. Two convenient methods to determine helical
      types were obtained. One method was obtained by calculating averaged helical
      parameters and the other was obtained by investigating meridional intensity
      distributions. The conformations of some peptides, such as aureobasidin E,
      ascidiacyclamide, synthetic analogues of heat-stable enterotoxin, were studied by
      an x-ray diffraction method, and in some cases, with the help of nmr spectroscopy
      and molecular mechanics calculations. Since these peptides have physiologically
      important activities, the structure-activity relationships of these peptides were
      discussed. Several other peptide structures and the polymorphism of amino acids
      are also reported.

PMID- 8541450
TI  - Molecular biology in reproductive endocrinology.
AB  - Through the study of naturally occurring mutations in humans, the creation of
      mutations by site-directed mutagenesis, and the production of transgenic knockout
      mice, further understanding of molecular reproductive endocrinology had been
      achieved. Mutations in the aromatase gene in females have confirmed that its
      deficiency results in a previously unrecognized form of sexual ambiguity with a
      46,XX karyotype, and delayed puberty with multicystic ovaries. It has long been
      known that estrogen is necessary for skeletal growth and epiphyseal closure in
      the female, but aromatase and estrogen receptor gene mutations in men have
      demonstrated for the first time, that estrogen is important for epiphyseal
      closure in the male. Mutations in the steroidogenic acute regulatory protein have
      been recently described that demonstrate the cause for lipoid congenital adrenal
      hyperplasia, a disorder characterized by the complete lack of steroid production.
      New gene mutations in gonadotropin beta-subunits, pituitary hormones, G-protein
      coupled receptors, G-proteins, steroid enzymes and their receptors have also been
      characterized recently. Site-directed mutagenesis experiments and transgenic
      knockout mice have been increasingly used to study the effects of normal
      endocrine function. Normal functions of steroid receptor genes (steroidogenic
      factor-1, estrogen receptor, progesterone receptor) the glycoprotein alpha
      subunit, luteinizing hormone beta, and proto-oncogenes such as RET have been
      better characterized by creating knockout models. Molecular biology techniques
      permit these types of studies which may be difficult, if not impossible, to
      perform otherwise in physiologic settings.

PMID- 8541451
TI  - Polycystic ovarian disease: a new look at an old subject.
AB  - The understanding of the pathogenesis of polycystic ovary syndrome has advanced
      significantly, and improvements have been made in the treatment of the commonly
      associated symptoms. New data continue to implicate a derangement in insulin
      secretion and metabolism as a cause of the disease. Therapeutic regimens for
      those patients unsuccessfully treated by traditional approaches have been further
      validated, especially for the treatment of infertility. Future therapeutic
      strategies involving the retrieval of unstimulated, immature oocytes that are
      fertilized and matured in vitro are a possibility.

PMID- 8541452
TI  - Advances in the diagnosis and treatment of the hirsute patient.
AB  - Most patients with hirsutism demonstrate hyperandrogenemia, which may be caused
      by polycystic ovary syndrome, nonclassic congenital adrenal hyperplasia, insulin
      resistance and, occasionally, neoplasms. In this review, current methods of
      diagnosis and recent advances in the medical treatment of hirsutism and
      hyperandrogenemia are discussed, including the use of gonadotropin-releasing
      hormone analogs, flutamide, spironolactone, finasteride, and ketoconazole.

PMID- 8541453
TI  - Habitual abortion: endocrinological aspects.
AB  - Endocrine disorders are among the potential causes of repeated spontaneous
      abortion although their role is uncertain. These disorders most frequently
      associated with repeated spontaneous abortion are corpus luteum insufficiency,
      polycystic ovary syndrome, diabetes mellitus, and hypo- and hyperthyroidism. The
      best method of diagnosing corpus luteum insufficiency has not yet been
      established. It seems that treatment for this condition cannot be based on simple
      supplementation with progesterone, but ovulation induction preceded by pituitary
      suppression and human chorionic gonadotropin administration might be more
      successful. There is increasing evidence that polycystic ovary syndrome is a
      cause of repeated spontaneous abortion, but possibly only in the presence of
      oligomenorrhea and luteinizing hormone hypersecretion. Diabetes, if well
      controlled by treatment, and thyroid dysfunction, probably play a minor role.

PMID- 8541454
TI  - Recurrent pregnancy loss.
AB  - This review of recurrent pregnancy loss examines our current understanding of the
      major etiologies of this unfortunate condition including genetic and endocrine
      abnormalities, anatomic variations, autoimmune conditions, alloimmune problems,
      systemic disease, and infection. Diagnostic protocols and treatment strategies
      are briefly presented. With a high rate of spontaneous normal pregnancy outcome,
      great care must be taken to do more good than harm.

PMID- 8541455
TI  - Thyroid dysfunction: an adolescent gynecologic perspective.
AB  - Abnormalities of thyroid function may cause irregularity or absence of the
      menstrual period, inhibit pubertal development and linear growth, and suppress
      reproductive function. Furthermore, pregnancy may itself affect thyroid function.
      New information is presented about the diagnosis and treatment of various forms
      of congenital and acquired thyroid disease. Issues ranging from the molecular
      biology of thyroid hormone resistance to public health measures developed to
      eliminate endemic goiter are addressed.

PMID- 8541456
TI  - Anorexia nervosa: issues for the obstetrician and gynecologist.
AB  - Anorexia nervosa, primarily a disorder in adolescent and young women, is not only
      a psychiatric illness; the disorder can have serious gynecologic and medical
      ramifications. As obstetricians and gynecologists assume a broader role in
      preventative medicine and health maintenance, an awareness is needed in the
      latest issues regarding this relatively common disorder. These issues include the
      newly recognized effects on the neuroendocrine system and the possible
      implications for treatment, the relationship of anorexia nervosa with a history
      of childhood sexual abuse and the possible implications of maternal anorexia
      nervosa on infant development.

PMID- 8541457
TI  - Ambulatory urodynamics.
AB  - Ambulatory monitoring of lower and upper urinary tract continues to develop. The
      addition of electronic urine-loss measurements to indicate the exact time-related
      loss is an important new feature. In the near future, quantitative urine-loss
      measurements will become available. The additional possibility of plugging in a
      flowmeter completes the technique with respect to pressure-flow analysis. At
      present, however, ambulatory urodynamics is still confined to specialized
      urodynamic centers. Ambulatory urodynamic monitoring has shown that de-novo
      detrusor instability after a suspension operation is frequently missed as a
      preoperative diagnosis of detrusor overactivity. The first steps are being taken
      toward giving a quantitative analysis of detrusor activity during the filling
      phase. This justifies a more widespread use of this ambulatory monitoring.

PMID- 8541458
TI  - Imaging of the lower urinary tract.
AB  - Review of the current literature indicates that the application of various
      ultrasound techniques plays the most important role in research of imaging of the
      lower urinary tract. Whereas sonographic urethrocystography by perineal,
      introital, or vaginal ultrasound has replaced radiography in routine clinical
      use, more detailed information about the urethra and periurethral tissues has
      been obtained by three-dimensional sonography and intraluminal high frequency
      ultrasound. Magnetic resonance imaging is emerging as the newest technique in
      this field, and has the potential to expand our knowledge of interactions of the
      lower urinary tract and the pelvic floor.

PMID- 8541459
TI  - Conservative management of incontinence.
AB  - This review evaluates the main conservative treatments (general measures,
      physiotherapy, electrostimulation, mechanical devices, and bladder retraining)
      with particular emphasis on their effectiveness in the management of urinary
      incontinence. This is difficult because of the paucity of clinical comparison
      studies using objective end points, and further work needs to be done to
      establish more clearly the effectiveness of these measures. However, because the
      therapies are of low risk, relatively low cost and are reversible, they should be
      included in the counselling of all incontinent patients regarding treatment
      options.

PMID- 8541460
TI  - Injectables in the treatment of female stress incontinence.
AB  - The failure to store urine resulting from bladder outflow incompetence requires a
      method to increase outflow resistance. Peri- and intraurethral injection is one
      form of treatment capable of accomplishing this need. The best results are
      obtained in those women who do not have detrusor abnormalities, who have adequate
      bladder capacity, who have no anatomic abnormality, and have demonstrable
      intrinsic sphincteric deficiency of function. The technique is tolerated well by
      patients and reduces the need for alternative major open surgical procedures.

PMID- 8541461
TI  - Laparoscopic surgery for incontinence and genitourinary prolapse.
AB  - Surgery with the aid of a laparoscope has enabled the surgeon to visualize the
      pelvic viscera and supports with new clarity. This has also enabled procedures
      normally performed through a laparotomy incision to be performed without a large
      incision. Generally, this results in a reduction in postoperative pain and a
      reduced convalescence time. The first reports for bladder neck surgery are
      encouraging, but longer-term follow up is required before a full appraisal of
      these new techniques can be made.

PMID- 8541462
TI  - Complications of urogynaecological surgery.
AB  - Operations to correct stress urinary incontinence are common procedures and are
      performed by both urologists and gynaecologists. Many surgeons, however, have not
      received subspecialty training. This review is intended to guide the surgeon in
      the prevention and management of the more common complications that may occur,
      such as de novo detrusor instability, voiding dysfunction, and the
      colposuspension syndrome.

PMID- 8541463
TI  - Quality of life and urinary incontinence.
AB  - Urinary incontinence affects some aspect of the lives of between 15 and 30% of
      women. The impact of incontinence, however, varies owing to many factors such as
      age and cultural beliefs. Quality of life assessments now offer both general and
      specific questionnaires that measure the impact of this debilitating condition.
      Although currently an important research tool, these assessments may ultimately
      become routine in clinical practice.

PMID- 8541464
TI  - Management of supraventricular tachycardia in the fetus.

PMID- 8541465
TI  - Do auditory stimuli activate human parietal brain regions?

PMID- 8541466
TI  - Reply--dipole problems.

PMID- 8541467
TI  - The suprachiasmatic area in the female hamster projects to neurons containing
      estrogen receptors and GnRH.
AB  - This study investigated whether the circadian regulation of luteinizing hormone
      (LH) release may be through direct input of the suprachiasmatic nucleus (SCN) to
      estrogen receptor (ER)- and/or gonadotropin releasing hormone (GnRH)
      immunoreactive neurons. We used Phaseolus vulgaris leucoagglutinin (PHA-L) as an
      anterograde tracer of SCN efferents and performed double label
      immunocytochemistry for PHA-L and ER or GnRH. Between 8 and 30% of ER cells and
      11-13% of the GnRH cells showed appositions with SCN efferents. Efferent
      projections of the subparaventricular hypothalamic nucleus and the
      retrochiasmatic area, relay stations of the circadian system, also made
      appositions with these two cell types. Results suggest that the circadian system
      could regulate the timing of the LH surge via two pathways, through input to GnRH
      and to ER cells.

PMID- 8541468
TI  - Brain mechanisms in human classical conditioning: a PET blood flow study.
AB  - Five healthy male subjects participated in a classical conditioning experiment,
      and positron emission tomography (PET) was used to compare regional cerebral
      blood flow before and after conditioning. The subjects participated in three
      different experimental phases. In the first (habituation) phase they listened to
      24 repetitions of a tone with random intervals. In the second (acquisition)
      phase, the tone was paired with a brief shock to the wrist. In the third
      (extinction) phase, the tone was presented alone again. 15OPET scans were taken
      during the habituation and extinction phases. Because the habituation and
      extinction phases were similar, any difference in blood flow to the tones
      presented during extinction probably reflected conditioning that occurred during
      the acquisition phase. Statistical parametric mapping (SPM) analysis of the PET
      data showed significantly increased activation in the right hemisphere in the
      orbito-frontal cortex, dorsolateral prefrontal cortex, inferior and superior
      frontal cortices, and inferior and middle temporal corticies. The only activated
      areas in the left hemisphere were area 19 and the superior frontal cortex. The
      results are interpreted as evidence for the involvement of cortical areas in
      human classical conditioning.

PMID- 8541469
TI  - Electrophysiological and morphological evidence for a new projection of LMAN
      neurones towards area X.
AB  - Neuronal connectivity of brain areas involved in song learning and song
      production was studied in the in vitro slice preparation of the zebra finch brain
      by electrophysiological intracellular recording techniques and by micro
      injections of the fluorescent tracer tetramethyl-rhodamine-dextran-amine. While
      validating some of the known projections to be preserved in the in vitro slice
      preparation, we were also able to identify a new projection from neurones of the
      lateral portion of the magnocellular nucleus of the anterior neostriatum towards
      area X of the lobus parolfactorius.

PMID- 8541470
TI  - Modifications in end positions of arm movements following short-term saccadic
      adaptation.
AB  - We investigated whether short-term saccadic adaptation modifies hand pointing.
      Subjects were presented with double-step targets, the second target jump
      occurring during the saccade to the first one and bringing the target back to 66%
      of the first target eccentricity, in order to reduce the gain of their gaze
      saccades. Before and after this adaptation phase, they pointed with their hand to
      single step targets while keeping their gaze straight ahead. The results show
      that the hand movements terminated at positions that were significantly less
      eccentric following the adaptation phase, resembling the adaptive modification
      seen in the gaze movements. These results suggest that the motor systems
      controlling gaze and hand use common information about target position.

PMID- 8541471
TI  - Trunk and head stabilization during the first months of independent walking.
AB  - This study measured the rate of acquisition of head and trunk postural control
      during the two early developmental periods of independent walking, as defined by
      global gait parameters. Gait parameters were observed longitudinally in four
      children. The maximum angular deviations of the trunk and head oscillations were
      computed in the frontal and sagittal planes. These decreased most dramatically
      during the first 10-15 weeks of independent walking, during the same period when
      global gait parameters changed rapidly. This head and trunk stabilization may be
      a fundamental process that help to maintain equilibrium during walking, and may
      be a necessary step prior to the development of fine posturo-motor control.

PMID- 8541472
TI  - Modeling other minds.
AB  - Nine normal volunteers performed a 'theory of mind' task while their regional
      brain blood flow pattern was recorded using the PET [15O]H2O technique. Control
      conditions induced subjects to attend to the visual and semantic attributes of
      known objects. In a third condition, subjects had to infer the function of an
      unfamiliar object from its form. In the 'theory of mind' condition, subjects had
      to infer function based on the form of both familiar and unfamiliar objects and
      in addition, model the knowledge and rationality of another mind about the
      function of these objects. Performance during the 'theory of mind' condition
      evoked the activation of a distributed set of neural networks with prominent
      activation of the left medial frontal lobe (Brodmann area 9) and left temporal
      lobe (Brodmann areas 21, 39/19, 38). This result suggests that when inferential
      reasoning depends on constructing a mental model about the beliefs and intentions
      of others, the participation of the prefrontal cortex is required. When access to
      such knowledge is affected by central nervous system dysfunction, such as that
      found in autism, modeling other minds may prove difficult.

PMID- 8541473
TI  - Experimental deposition of Alzheimer amyloid beta-protein in canine
      leptomeningeal vessels.
AB  - To study the pathogenesis of cerebral amyloid angiopathy (CAA), organ cultures of
      canine leptomeninges were incubated with fluorescein-conjugated amyloid beta
      protein (FA beta, residues 1-40; 10 nM to 200 microM). Fluorescence microscopy
      showed focal and dose-dependent FA beta binding to blood vessels affected by CAA
      at FA beta-concentrations as low as 10 nM. The new A beta deposits appeared to be
      extracellular and were localized to the middle and outer layers of leptomeningeal
      arterioles. FA beta partially co-localized with apolipoprotein E (ApoE) as
      revealed by confocal microscopy, suggesting that A beta in situ binds to ApoE.
      Young dogs or old dogs without CAA showed no deposition of FA beta. Our results
      indicate that after initiation of CAA pathology, physiological concentrations of
      soluble A beta are sufficient to sustain its further deposition and therefore the
      progression of CAA.

PMID- 8541474
TI  - Temporal changes in meal number and meal size relationship in response to rHu IL
      1 alpha.
AB  - Peripherally infused interleukin-1 reduces food intake. Its temporal and
      selective effects on meal number and meal size were investigated in seven rats
      continuously infused for 3 days with recombinant human interleukin-1 alpha (rHu
      IL-1 alpha; 3 micrograms day-1, i.v.). Food intake decreased significantly during
      the first two infusion days, and was brought about by first the early reduction
      of meal number, followed by meal size with a 1 day delay. The primary effect of
      rHu IL-1 alpha was seen during the dark cycle. After the infusion was stopped,
      meal number recovered most quickly, followed by a lag in recovery of meal size.
      We conclude that rHu IL-1 alpha influenced food intake primarily via an effect on
      meal number, which responds more rapidly than a decrease in meal size, thereby
      inducing an immediate decrease in food intake.

PMID- 8541475
TI  - Localization of N-ethylmaleimide-sensitive fusion protein in pinealocytes.
AB  - N-ethylmaleimide-sensitive fusion protein (NSF), a protein necessary for
      vesicular docking and/or fusion, was detected immunohistochemically in
      pinealocytes. NSF was distributed similarly to synaptophysin and vacuolar-type
      H(+)-ATPase (V-ATPase), marker proteins for synaptic-like microvesicles (MVs)
      abundantly present in pinealocytes. A subcellular fractionation study indicated
      that .> 95% of NSF was present as a membrane-bound form and that some NSF was
      associated with MVs. Like neuronal NSF, the protein was not solubilized from
      membranes with either 2 mM Mg-ATP or 2% sodium carbonate, suggesting that NSF was
      tightly bound to the membranes. NSF was also detected in purified MVs from bovine
      posterior pituitaries. Since MVs are the organelles in which transmitters are
      stored, these results suggest that NSF is involved in the MV-mediated exocytosis
      of transmitters from endocrine cells.

PMID- 8541477
TI  - DNA fragmentation and activation of c-Jun in the cerebellum of mutant mice
      (weaver, Purkinje cell degeneration).
AB  - Weaver and Purkinje cell degeneration (pcd) are autosomal recessive mutations in
      the mouse characterized by an almost complete loss of cerebellar Purkinje
      neurones and granule cells, respectively. Developmental neuronal death occurs by
      activation of an apoptotic pathway and chromatin condensation has been observed
      in degenerating granule cells of weaver mutants. In the present study we
      demonstrate nuclear DNA fragmentation in Purkinje cells of pcd mice and in
      granule cells of weaver mutants during the period of neuronal degeneration using
      in situ end labelling by terminal transferase and fluorescein-dUTP. Furthermore,
      activation of candidate cell death effector gene c-jun has been detected
      exclusively within the affected cell populations by immunohistochemistry. Both
      labelled DNA fragments and nuclear c-Jun immunoreactivity were virtually absent
      in wild-type animals. Thus, genetically determined cell death in pcd and weaver
      mutant mice has features of apoptosis and may require activation of cell death
      effector genes.

PMID- 8541476
TI  - A calcium-permeable cGMP-activated cation conductance in hippocampal neurons.
AB  - Whole-cell patch clamp recordings detected a previously unidentified cGMP
      activated membrane conductance in cultured rat hippocampal neurons. This
      conductance is nonselectively permeable for cations and is completely but
      reversibly blocked by external Cd2+. The Ca2+ permeability of the hippocampal
      cGMP-activated conductance was examined in detail, indicating that the underlying
      ion channels display a high relative permeability for Ca2+. The results indicate
      that hippocampal neurons contain a cGMP-activated membrane conductance that has
      some properties similar to the cyclic nucleotide-gated channels previously shown
      in sensory receptor cells and retinal neurons. In hippocampal neurons this
      conductance similarly could mediate membrane depolarization and Ca2+ fluxes in
      response to intracellular cGMP elevation.

PMID- 8541478
TI  - Neuroamine related compounds in the CSF of hydrocephalic rabbits.
AB  - The effects of neonatal hydrocephalus on the levels of tyrosine, tryptophan, 5
      hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) in CSF were
      determined by high-performance liquid chromatography (HPLC) with fluorometric
      detection in normal and chronically hydrocephalic rabbits. The hydrocephalic
      rabbits showed a highly significant increase in both the serotonin metabolite 5
      HIAA and the dopamine metabolite HVA. There were no significant effects of the
      hydrocephalus on either tyrosine or tryptophan levels. There was a significant
      positive correlation between the intracranial pressure (ICP) and the increase in
      5-HIAA and HVA, but not with the two precursor amino acids. There was a
      significant decrease in these amino acid precursors with age in both groups. A
      trend towards higher levels of 5-HIAA and HVA in older rabbits was also evident,
      however this change was not to the degree found in the hydrocephalics. These data
      indicate that increased ICP affects the mechanism of removal of 5-HIAA and HVA
      from the cerebrospinal fluid.

PMID- 8541479
TI  - Electrical stimulation of the sciatic nerve alters neuropeptide content and
      lymphocyte migration in the subcutaneous tissue of the rat hind paw.
AB  - To study the possible mechanism by which peripheral nerves mediate immune
      responses in target tissues, electrical stimulation of the sciatic nerve was
      combined with subcutaneous microdialysis of the hind paw. Following unilateral
      stimulation of the sciatic nerve, an ipsilateral rise in substance P and a
      bilateral rise in VIP levels were observed in dialysate samples from experimental
      vs control animals. Electrical stimulation of the sciatic nerve induced a marked
      hyperemia and swelling of the ipsilateral paw. Quantitative immunocytochemical
      analysis of paraffin-embedded sections of the hind foot pads demonstrated T
      lymphocyte migration ipsilateral to the stimulated nerve. These findings suggest
      that peripheral nerves can directly modulate local immune and inflammatory
      responses.

PMID- 8541480
TI  - Effects of phenytoin on the persistent Na+ current of mammalian CNS neurones.
AB  - Whole-cell recordings in voltage-clamp mode were performed on acutely isolated
      neurones from rat neocortex and neostriatum to examine the effects of the
      anticonvulsant phenytoin on a non-inactivating (persistent) Na+ current (INaP).
      INaP was chosen because it enhances neuronal excitability near firing threshold,
      which makes it a potential target for anticonvulsant drugs. In both preparations,
      phenytoin (10-100 microM) inhibited INaP in a dose-dependent fashion without
      altering the voltage-dependence of current activation. On average, half-block of
      INaP was produced by 34 microM phenytoin suggesting that therapeutic drug
      concentrations are likely to affect INaP. Inhibition of INaP might represent a
      novel mechanism contributing to the anticonvulsant profile of phenytoin.

PMID- 8541481
TI  - Visual-spatial localization by patients with frontal-lobe lesions invading or
      sparing area 46.
AB  - Monkeys with unilateral principal sulcus (PS) lesions show a contralateral
      deficit in localizing remembered targets, especially as the recall interval is
      lengthened. We tested 20 patients with unilateral frontal-lobe excisions that
      invaded (FI) or spared (FS) area 46 (putative homologue of PS) and 32 normal
      controls (NC) on a task where subjects had to indicate the location of a light
      dot either immediately, or after 30 s, with or without interference. The FI group
      was worse than the NC group following both delay conditions. NC and FS groups
      differed only after interference. We concluded that area 46 is involved in
      recalling the location of visual targets, but unlike the monkey, the deficit is
      not restricted to a particular part of the visual field.

PMID- 8541482
TI  - Focal cerebral ischemia induces CRH mRNA in rat cerebral cortex and amygdala.
AB  - Corticotropin-releasing hormone (CRH) antagonism has neuroprotective effects in
      models of ischemia. We examined CRH mRNA by in situ hybridization in a well
      established rat model of focal cerebral ischemia caused by permanent middle
      cerebral artery occlusion (MCAo). In ischemic cortex CRH mRNA levels were
      elevated 2.6-fold 60 min after MCAo, compared with sham operated animals. CRH
      mRNA was also induced in the amygdala, 60 min following ischemia, in a pattern
      which was qualitatively different from that of sham operated animals. This rapid
      and profound increase in CRH mRNA levels during focal cerebral ischemia is likely
      to be associated with neurotoxicity, as CRH antagonism has been reported to cause
      a significant reduction in neuronal loss during ischemia.

PMID- 8541483
TI  - Effect of 7-nitro indazole on quinolinic acid-induced striatal toxicity in the
      rat.
AB  - Nitric oxide (NO) is implicated as a mediator of cell death in models of
      neurodegenerative disease. However, the precise role of NO in neuronal
      degeneration remains controversial. In the present study we employed 7-nitro
      indazole (7-NI), reportedly a selective inhibitor of neuronal nitric oxide
      synthase (nNOS) in vivo, to investigate the possible involvement of NO in
      quinolinic acid (QA)-induced striatal toxicity in the rat. Intrastriatal
      injection of QA (30 nmol) caused loss of NADPH diaphorase (48%), NOS (48%) and
      acetylcholinesterase (AChE; 22%) positive neurones and a loss of NOS activity
      (78%) in striatal homogenates. 7-NI (30 mg kg-1, i.p. every 4 h for 20 h) did not
      affect the loss of NADPH diaphorase (52%), NOS (52%) and AChE (16%) positive
      neurones or the loss of NOS activity (66%) in striatal homogenates. The present
      study does not support a role for NO in QA-induced striatal toxicity.

PMID- 8541484
TI  - Chronic haloperidol potentiates stimulated glutamate release in caudate putamen,
      but not prefrontal cortex.
AB  - Rats were given haloperidol continuously for 6 months via subcutaneous implants.
      Extracellular concentrations of basal and high K(+)-stimulated GABA and glutamate
      in the lateral caudate putamen and the medial prefrontal cortex were then
      assessed using microdialysis. While there were no significant differences in
      basal extracellular concentrations in either brain region, chronic haloperidol
      treated rats showed significantly greater increases in glutamate following
      stimulation with high K+ in the caudate putamen, but not the prefrontal cortex.
      This effect was accompanied by an attenuation of K(+)-stimulated GABA overflow in
      the caudate putamen. These results suggest regionally selective alterations in
      amino acid transmitter function which may be related to chronic neuroleptic
      induced motor side effects.

PMID- 8541485
TI  - Metabotropic glutamate receptors in the guinea-pig medial vestibular nucleus in
      vitro.
AB  - Despite the accumulation of a large body of evidence on the function of the
      kainate/alpha-amino-3-5-methyl-4-iso-xazolepropionic acid (AMPA) and N-methyl-D
      aspartate (NMDA) excitatory amino acid (EAA) receptor subtypes within the
      vestibular nucleus, little is known of the metabotropic receptor subtype. The aim
      of the present study was to examine the response of guinea-pig medial vestibular
      nucleus (MVN) neurons in brain stem slices to the selective metabotropic receptor
      agonist, 1S,3R-amino-cyclopentyl-1,3-dicarboxylate (ACPD). Sixty percent (12/20)
      of MVN neurones responded to 1S,3R-ACPD at a concentration of 10(-6) M, compared
      with 40% (8/20) and 35% (7/20) of neurones at concentrations of 10(-8) and 10(
      10) M. Both increases and decreases in firing rate were observed in different
      neurones: in general, the magnitude of the responses was large and the duration
      of the responses was long. Recordings from a slice which contained only the MVN
      confirmed that these responses were produced by the action of the metabotropic
      agonist within the MVN itself. These results demonstrate that many MVN neurones
      have functional metabotropic receptors.

PMID- 8541486
TI  - Age-related functional differences between auditory cortices: a whole-head MEG
      study.
AB  - Auditory evoked magnetic fields (AEFs) were recorded from 10 healthy younger and
      10 older subjects using a whole-head magnetometer. Two blocks of tone pips were
      presented to the left ear with constant inter-stimulus intervals (ISIs) of 0.5
      and 2.5 s. The amplitude of P50m, unlike that of N100m, was larger in the older
      subjects. In both groups, the peak latencies of P50m and N100m responses were
      significantly shorter over the contralateral than ipsilateral cortex. The
      interhemispheric latency difference of N100m was significantly increased with
      age. These findings suggest that ageing delays signal processing in the
      ipsilateral auditory cortex and that ageing affects consecutive AEFs in a
      different manner.

PMID- 8541487
TI  - The relationship between quantal content and delayed quantal release.
AB  - Following an endplate potential there is a period of elevated spontaneous quantal
      release, known as delayed release. We have estimated the relationship between
      evoked quantal release and delayed release in two ways. First, in a solution in
      which the Na+ was replaced with methylamine, the number of delayed release evoked
      by electronic depolarization of the nerve terminal changed little over a 30-fold
      range of output. Second, we varied [Ca2+]out stepwise in Na solution with added
      Mg2+ and measured delayed release and EPP amplitude at single junctions. Over
      much of the range, elevating the EPP amplitude many-fold increased delayed
      release only slightly, if at all. Our interpretation is that the effects of
      residual Ca2+ are not proportional to the amount of Ca2+ entering to trigger
      quantal release.

PMID- 8541488
TI  - Beta-adrenoreceptor activation reduces dye-coupling between immature rat
      neocortical neurones.
AB  - The present study examined the effect of activation of adrenergic receptors by
      noradrenaline and the beta-receptor selective agonist isoproterenol on dye
      coupling between developing lamina II/III pyramidal neurones in rat prefrontal
      and sensorimotor cortex. To assess dye-coupling neurones were intracellularly
      injected with neurobiotin. Under control conditions injections performed in
      slices obtained from neonatal rats (7-10 postnatal days) resulted in clusters of
      more than 30 tracer-coupled neurones. Preincubation with either isoproterenol or
      noradrenaline reduced the number of coupled cells by 60-80%. The effect of
      isoproterenol was suppressed by the beta 1-adrenoreceptor antagonist atenolol.
      Our results indicate that modulation of gap junction coupling between
      differentiating neocortical neurones might be one important function of
      noradrenergic afferents during early postnatal development of the neocortex.

PMID- 8541489
TI  - Parabanic acid for monitoring of oxygen radical activity in the injured human
      brain.
AB  - The authors used intracerebral microdialysis to harvest allantoin and parabanic
      acid, potential markers of in vivo oxygen radical activity, from the frontal lobe
      cortex of three patients in the neurointensive care unit after serious aneurysmal
      subarachnoid haemorrhage. Clinical events involving severe secondary ischaemia,
      ultimately leading to structural damage, were associated with a dramatic
      elevation of the microdialysate level of parabanic acid, whereas allantoin showed
      less robust changes. In one patient with an uneventful clinical course and
      without signs of secondary ischaemia parabanic acid levels remained low. The
      results support the involvement of highly reactive oxygen radical species in
      human cerebral ischaemia. Parabanic acid appears to be an important marker of
      free radical reactions in vivo and may be used to monitor free radical activity
      and to evaluate pharmacological therapy with radical scavengers.

PMID- 8541490
TI  - Senescence-induced expression of a homologue of delta 9 desaturase in rose
      petals.
AB  - cDNAs for senescence-inducible genes were isolated by differential hybridization
      from a cDNA library derived from mRNAs from the petals of rose flowers. The amino
      acid sequence deduced from these cDNAs exhibited significant homology to those of
      delta 9 acyl-lipid desaturases of cyanobacteria and of delta 9 acyl-CoA
      desaturases of a yeast and mammals. There was no amino-terminal sequence
      indicative of a leader peptide for targeting to the chloroplasts or to
      mitochondria. Northern blot analysis indicated that the transcripts of the cDNAs
      were expressed specifically in petals at late developmental stages and during
      senescence. It is proposed that a delta 9 desaturase in the senescing petals play
      an important role in the degradation of saturated fatty acids of membrane lipids.

PMID- 8541491
TI  - Comparison of different constitutive and inducible promoters for the
      overexpression of transgenes in Arabidopsis thaliana.
AB  - We compared the organ specificity and the strength of different constitutive
      (CaMV-35S, CaMV-35Somega, Arabidopsis ubiquitin UBQ1, and barley leaf thionin
      BTH6 promoter) and one inducible promoter (soybean heat-shock promoter Gmhsp17.3)
      in stably transformed Arabidopsis thaliana plants. For this purpose we
      constructed a set of plant expression vectors equipped with the different
      promoters. Using the uidA reporter gene we could show that the CaMV-35S promoter
      has the highest expression level which was enhanced two- to threefold by the
      addition of a translational enhancer (TMV omega element) without altering the
      organ specificity of the promoter. The barley leaf thionin promoter was almost
      inactive in the majority of lines whereas the ubiquitin promoter exhibited an
      intermediate strength. The heat-shock promoter was inducible up to 18-fold but
      absolute levels were lower than in the case of the ubiquitin promoter. Conclusive
      quantitative results for different organs and developmental stages were obtained
      by the analysis of 24 stably transformed lines per promoter construct.

PMID- 8541492
TI  - Molecular cloning and expression analysis of peroxidase genes from wheat.
AB  - A PCR-based screening approach was used to isolate genomic clones from wheat
      encoding peroxidase isozymes. Three complete genes (pox1, pox2 and pox4) and one
      truncated gene (pox3) were characterized. The nucleotide sequences predicted
      mature proteins of 31 kDa, in which all the highly conserved motifs of secreted
      plant peroxidases were preserved. The coding regions showed 73-83% DNA sequence
      identity, with the highest level of similarity noted for the tandemly oriented
      pox2 and pox3. Expression of respective pox genes in various tissues of wheat was
      assessed by the RT-PCR technique, which showed that all four genes are active.
      The primary pox1 mRNA was spliced to remove three introns, whereas processing of
      the other pox transcripts involved only two intervening sequences. Splicing
      occurred at consensus GU/AG splice sites except for the first introns of pox1,
      pox2 and pox4 transcripts, where processing took place at unusual GC donor sites.
      The RNA analysis suggested that the pox1, pox2 and pox4 genes are predominantly
      expressed in roots. Lower levels of expression were found for pox4 and pox3 in
      leaves. Infection of wheat by the powdery mildew fungus selectively induced
      expression of pox2 in leaves.

PMID- 8541493
TI  - Genomic structure and expression of the pyruvate, orthophosphate dikinase gene of
      the dicotyledonous C4 plant Flaveria trinervia (Asteraceae).
AB  - Pyruvate orthophosphate dikinase (PPDK) is a key enzyme of C4 photosynthesis
      providing the acceptor molecule for the primary CO2 fixation in the mesophyll
      cells. Here we present the isolation and characterisation of the corresponding
      gene (termed pdk) from the C4 plant Flaveria trinervia (Asteraceae). Southern
      analysis indicates that in contrast to maize pdk sequences in F. trinervia are
      present as single copy. Sequence analysis of the entire gene reveals that its
      coding sequence is identical to the previous isolated PPDK-cDNA from this
      species. The gene spans about 13 kb and consists of 21 exons, it thus contains
      two additional exons compared to the maize gene. As in maize, a long intervening
      sequence of 6.1 kb is positioned at the boundary of the transit peptide segment
      and the mature protein region. Pdk transcripts accumulate abundantly in leaves,
      but are also detectable in stems and roots. While the leaf and stem transcripts
      are 3.4 kb in size and encode the chloroplastic PPDK isoform, a 3.0 kb transcript
      lacking the region encoding the plastidic transit peptide accumulates in roots.
      Thus two different transcripts can be produced from a single pdk gene most likely
      by use of alternative promoters and not by alternative splicing. The accumulation
      of the 3.4 kb transcript is under light control. Darkening leads to a drastic
      depletion of this transcript in both leaves and stems. Instead, the 3.0 kb
      transit peptide-lacking pdk transcript accumulates, but only in stems and roots,
      not in leaves.

PMID- 8541494
TI  - Editing of the chloroplast ndhB encoded transcript shows divergence between
      closely related members of the grass family (Poaceae).
AB  - The ndhB-encoded transcript from barley chloroplasts deviates from the genomic
      ndhB sequence by nine C-to-U transitions, which is the maximum number of editing
      events for a chloroplast mRNA reported so far. Comparison with ndhB transcripts
      from other chloroplast species shows that six of the nine editing sites observed
      in barley are structurally and functionally conserved in maize, rice and tobacco.
      The remaining three sites, however, show divergent patterns of conservation even
      within the three members of the grass family. The conservation of two of these
      sites in tobacco but not in the closely related graminean species suggests that
      divergence of the ndhB editing sites is caused by the loss of preexisting editing
      sites rather than by gain of new sites.

PMID- 8541495
TI  - Analysis of randomly isolated cDNAs from developing endosperm of rice (Oryza
      sativa L.): evaluation of expressed sequence tags, and expression levels of
      mRNAs.
AB  - Using a cDNA library prepared from poly(A)+ RNA from 10-day-old rice endosperm,
      partial nucleotide sequences of randomly isolated clones were analyzed. A total
      of 153 (30.6%) out of 500 cDNA clones showed high amino acid identity to
      previously identified genes. There was significant redundancy in cDNAs encoding
      prolamine and glutelin. About 21.0% of the cDNA clones were found to code for
      seed storage protein genes. Consequently, 37 independent genes were identified.
      Using cDNA clones encoding glutelin, prolamine, seed allergen, alpha-1,4-glucan
      branching enzyme, glycine-rich RNA binding protein, metallothionein, non-specific
      lipid-transfer protein and ubiquitin conjugating enzyme the accumulation of mRNA
      during rice seed development was compared. Genes associated with seed storage
      protein and starch biosynthesis were expressed according to expected
      developmental stages. Glycine-rich RNA binding protein genes as well as
      metallothionein-like protein genes were highly expressed in developing seeds, but
      low in leaves of whole plants.

PMID- 8541496
TI  - Members of a new family of DNA-binding proteins bind to a conserved cis-element
      in the promoters of alpha-Amy2 genes.
AB  - The promoters of wheat, barley and wild oat alpha-Amy2 genes contain a number of
      conserved cis-acting elements that bind nuclear protein, we report here the
      isolation of two cDNAs encoding proteins (ABF1 and ABF2) that bind specifically
      to one of these elements, Box 2 (ATTGACTTGACCGTCATCGG). The two proteins are
      unrelated to each other except for a conserved region of 56-58 amino acids that
      consists of 25 highly conserved amino acids followed by a putative zinc finger
      motif, C-X4-5-C-X22-23-H-X1-H. ABF1 contains two such conserved regions, whereas
      ABF2 possesses only one but also contains a potential leucine zipper motif,
      suggesting that it could form homo- or heterodimers. ABF1 and ABF2 expressed in
      Escherichia coli bound specifically to Box 2 probes in gel retardation
      experiments; this binding was abolished by the transition-metal-chelating agent,
      1,10-o-phenanthroline and by EDTA. We propose that ABF1 and ABF2 are
      representatives of two classes of a new family of plant sequence-specific DNA
      binding proteins.

PMID- 8541497
TI  - Activity of single-stranded DNA endonucleases in mung bean is associated with
      cell division.
AB  - A single-strand-specific endonuclease from mung bean sprouts is widely used in
      molecular biology. However, the biological role of this enzyme is unknown. We
      studied the spatial and temporal activity of single-stranded DNA endonucleases in
      mung bean seedling by following enzyme activity that linearizes supercoiled
      plasmid DNA, a characteristic of this type of enzyme. The formation of a linear
      molecule from supercoiled DNA was found to occur in two distinguishable steps.
      The first, which involves introducing a nick into the supercoiled DNA and
      relaxing it, is very rapid and complete within a few seconds. The second step of
      cleaving the opposite strand to generate a unit-length linear duplex DNA is a
      relatively slow process. Analysis of the DNA cleavage sites showed the nuclease
      preferentially cuts supercoiled DNA at an AT-rich region. Varying levels of
      nuclease activity could be detected in different tissues of the mung bean
      seedling. The highest activity was in the root tip and was correlated with
      histone H1 kinase activity. This implies a link between nuclease activity and
      cell division. Induction of cell division in mung bean hypocotyls with auxin
      promoted formation of root primordia and considerably increased the activity of
      single-stranded DNA endonucleases. The nuclease activity and histone H1 kinase
      activity were reduced in mung bean cuttings treated with hydroxyurea, but not in
      cuttings treated with oryzalin. The potential function of single-stranded DNA
      endonucleases is discussed.

PMID- 8541498
TI  - The maize transcription factor Opaque-2 activates a wheat glutenin promoter in
      plant and yeast cells.
AB  - The promoter of the wheat low-molecular-weight glutenin (LMWG1D1) gene contains a
      cis element called the GCN4 like motif (GLM) which has low homology to one class
      of binding site for the maize endosperm-specific b-ZIP transcription factor
      Opaque-2 (O2). Previous work has shown that the GLM element interacts with the
      nuclear factor ESBFII during wheat endosperm development at the time of maximum
      transcription of the LMWG1D1 gene. In this paper we demonstrate that O2 binds to
      the GLM element and can activate high levels of transcription from the wheat GLM
      in transient assays in plant protoplasts and in yeast cells. Lower levels of O2
      activation through the GLM element in yeast containing a defective GCN4 gene
      showed that GCN4 was necessary for high levels of O2 transcriptional activation,
      indicating that O2 may need to heterodimerise with GCN4 to activate transcription
      in yeast. These observations provide evidence that the GLM represents a new type
      of O2 DNA-binding site, and support a postulate that an O2 homologue may activate
      endosperm-specific expression of wheat storage protein genes.

PMID- 8541499
TI  - Transcription, splicing and editing of plastid RNAs in the nonphotosynthetic
      plant Epifagus virginiana.
AB  - Expression of the vestigial plastid genome of the nonphotosynthetic, parasitic
      flowering plant Epifagus virginiana was examined by northern analysis and by
      characterization of cDNAs. Probes for each of 12 plastid genes tested hybridized
      to all lanes of northern blots containing total RNA prepared from stems and
      fruits of Epifagus and from leaves of tobacco. Certain transcript patterns in
      Epifagus plastids are highly complex and similar to those of tobacco operons. In
      contrast, genes such as rps2, which have become orphaned in Epifagus as a result
      of evolutionary loss of formerly cotranscribed genes, show simpler transcript
      patterns in Epifagus than in tobacco. Sizing and sequencing of cDNAs generated by
      reverse transcriptase-PCR for three genes, rps12, rpl2, and clpP, show that their
      transcripts are properly cis- and/or trans-spliced at the same five group II
      intron insertion sites used in photosynthetic plants. A single, conventional C-
      >U edit in rps12 was found among the total of 1401 nucleotides of cDNA sequence
      that was determined for the three genes. An octanucleotide sequence identical to
      a putative guide RNA of plant organelles and perfectly complementary to the rps12
      edit site itself was identified just 200 bp upstream of the edit site. These
      data, together with previous results from the complete sequencing of the Epifagus
      plastid genome, provide compelling evidence that this degenerate genome is
      nonetheless expressed and functional. Analysis of the putative maturase MatK,
      encoded by the group II intron of trnK in photosynthetic land plants but by a
      freestanding gene in Epifagus, leads us to hypothesize that it acts 'in trans' to
      assist the splicing of group II introns other than the one in which it is
      normally encoded.

PMID- 8541500
TI  - Differential ethylene-inducible expression of cellulase in pepper plants.
AB  - Ethylene promotes the abscission of leaves and the ripening of fruits in pepper
      plants, and in both events an increase in cellulase activity is observed.
      However, two enzyme isoforms (pI 7.2 and 8.5, respectively) are differentially
      involved in the two physiological phenomena. The pI 8.5 form has been purified
      from ripe fruits. It is a glycoprotein with an apparent molecular mass of 54 kDa.
      Two short peptides were sequenced and a very high homology to a tomato cellulase
      was observed. Polyclonal antibodies, raised against the purified enzyme, have
      allowed us to demonstrate that the observed ethylene-induced increase in
      cellulase activity is paralleled by de novo synthesis of protein. Three cDNAs
      (CX1, CX2 and CX3), encoding different cellulases, were obtained and
      characterized and their expression investigated. Accumulation of all three mRNAs
      is induced by ethylene treatment, though to different levels. CX1 is mainly
      expressed in ripe fruits while CX2 is especially found in abscission zones. CX3
      accumulates at very low levels in activated abscission zones. Comparisons with
      other known cellulases demonstrate clear heterogeneity within the higher plant
      cellulases. Differences in ethylene inducibility and molecular structure suggest
      different physiological roles for cellulase in pepper plants.

PMID- 8541501
TI  - Functional analysis of linker insertions and point mutations in the alpha-Amy2/54
      GA-regulated promoter.
AB  - Functional analysis of a gibberellin-regulated wheat alpha-amylase promoter,
      alpha-Amy2/54, has indicated that three regions were essential for expression. By
      studying the ability of mutant promoters, containing a randomly inserted 22 bp
      excision linker, to direct expression in oat aleurone protoplasts we have refined
      the positions and extents of these three cis elements and also demonstrated the
      presence of two additional elements. By converting the linker insertions to
      either single base point mutations or deletions using the class IIS restriction
      endonuclease BsmI we have shown that nucleotides -119 and -109 within the GARE 
      121GTAACAGAGTCTGG-108 and nucleotide -152 within the proposed element 
      156GATTGACTTGACC-144 are essential for high level expression from this promoter.

PMID- 8541502
TI  - The promoter of the Vicia faba L. VfENOD-GRP3 gene encoding a glycine-rich early
      nodulin mediates a predominant gene expression in the interzone II-III region of
      transgenic Vicia hirsuta root nodules.
AB  - We recently reported on the broad bean gene VfENOD-GRP3 encoding a glycine-rich
      early nodulin. This gene was predominantly expressed in the interzone II-III
      region of Vicia faba root nodules. The VfENOD-GRP3 promoter contained several
      sequence motifs potentially involved in the regulation of gene expression. To
      investigate the molecular basis for the specific VfENOD-GRP3 expression, defined
      VfENOD-GRP3 promoter fragments were fused to an intron-containing gusAint gene.
      Agrobacterium rhizogenes ARqual strains carrying these fusions integrated into
      the TL DNA were used to generate hairy roots on Vicia hirsuta, which subsequently
      were nodulated. Histochemical analysis of transgenic nodules indicated that a
      strong gusAint expression in the interzone II-III region was mediated by the 
      1252/+10 VfENOD-GRP3 promoter region. This reporter gene expression in V. hirsuta
      was comparable to the location of VfENOD-GRP3 transcripts in V. faba nodules. An
      analysis of defined promoter fragments revealed that a strong gusAint expression
      in the interzone II-III region was also mediated by the -737/+10 promoter,
      whereas the -239/+10 promoter only mediated a weak gusAint expression in the
      interzone II-III region. Since the -239/+10 promoter fragment did not resemble
      published nodulin gene promoters, we propose that it contains new sequence motifs
      involved in mediating gene expression in the interzone II-III region of Vicia
      nodules.

PMID- 8541503
TI  - Molecular characterization and expression of alfalfa (Medicago sativa L.)
      flavanone-3-hydroxylase and dihydroflavonol-4-reductase encoding genes.
AB  - Flavonoids are plant phenolic compounds involved in leguminous plant-microbe
      interactions. Genes implied in the central branch (chalcone synthase (CHS),
      chalcone isomerase (CHI)) or in the isoflavonoid branch of the flavonoid
      biosynthesis pathway have been characterized in Medicago sativa. No information
      is available to date, however, on genes whose products are involved in the
      synthesis of other types of flavonoids. In this paper we present the genomic
      organization as well as the nucleotide sequence of one flavanone-3-hydroxylase
      (F3H) encoding gene of M. sativa, containing two introns and exhibiting 82-89%
      similarity at the amino acid level to other F3H proteins. This is the first
      report on the genomic organization of a f3h gene so far. We present also the
      sequence of a partial dihydroflavonol-4-reductase (DFR) M. sativa cDNA clone.
      Southern blot experiments indicated that f3h and dfr genes are each represented
      by a single gene within the tetraploid genome of M. sativa. By a combination of
      Northern blot and RT-PCR analysis, we showed that both f3h and dfr genes are
      expressed in flowers, nodules and roots, with a pattern distinct from chs
      expression. Finally, we show that dfr is expressed in M. sativa leaves whereas
      f3h is not. The role played by these two genes in organs other than flowers
      remains to be determined.

PMID- 8541504
TI  - A gibberellin-stimulated ubiquitin-conjugating enzyme gene is involved in alpha
      amylase gene expression in rice aleurone.
AB  - A ubiquitin-conjugating enzyme (UBC) gene, induced by gibberellin (GA) within an
      hour, was identified in rice (Oryza sativa) seeds by the mRNA differential
      display technique. GA inducibility was confirmed by RNA hybridization. A full
      length UBC cDNA clone and a genomic clone have been isolated and sequenced. The
      deduced amino acid sequence shares a significant identity with several known UBC
      sequences, which are probably involved in the pathway responsible for degrading
      short-lived regulatory proteins. In vivo transient assays using the UBC gene
      promoter, joined to the luciferase cDNA as the reporter gene, showed that the
      sequence located between positions 231 and 159 upstream of the transcription
      start site of this promoter is crucial for GA-dependent activation of the
      luciferase cDNA. Finally, trans-activation experiments indicated that this UBC
      gene is involved in gibberellin-stimulated alpha-amylase gene expression.

PMID- 8541505
TI  - Functional characteristics of the maize RNA-binding protein MA16.
AB  - The maize RNA-binding protein MA16 is a non-ribosomal nucleolar protein widely
      distributed in different maize tissues. We have previously shown that the MA16
      protein binds preferentially to guanosine- and uridine-rich sequences. As a step
      towards the identification of specific targets with which MA16 interacts within
      the cell, we investigated the RNA-binding affinities and several other aspects of
      the protein by using binding assays and immunochemistry. The MA16 protein showed
      a wide spectrum of RNA-binding activities with lower affinities to several RNAs
      that was salt and heparin-sensitive indicative of electrostatic interactions, and
      higher affinities to particular RNAs including rRNA and translatable mRNA
      sequences. Among the RNAs found associated with MA16 protein was that encoding
      MA16 itself. This observation raises the possibility that MA16 gene expression
      could be self-regulated. Immunoprecipitation studies showed that in vivo MA16 was
      phosphorylated and that MA16 interacts with RNAs through complex association with
      several proteins. These results suggest that both phosphorylation and interaction
      with other proteins may be involved in determining RNA-binding specificities of
      MA16 in the cell.

PMID- 8541506
TI  - Evidence for the thiamine biosynthetic pathway in higher-plant plastids and its
      developmental regulation.
AB  - Thiamine or vitamin B-1, is an essential constituent of all cells since it is a
      cofactor for two enzyme complexes involved in the citric acid cycle, pyruvate
      dehydrogenase and alpha-ketoglutarate dehydrogenase. Thiamine is synthesized by
      plants, but it is a dietary requirement for humans and other animals. The
      biosynthetic pathway for thiamine in plants has not been well characterized and
      none of the enzymes involved have been isolated. Here we report the cloning and
      characterization of two cDNAs representing members of the maize thi1 gene family
      encoding an enzyme of the thiamine biosynthetic pathway. This assignment was made
      based on sequence homology to a yeast thiamine biosynthetic gene and by
      functional complementation of a yeast strain in which the endogenous gene was
      inactivated. Using immunoblot analysis, the thi1 gene product was found to be
      located in a plastid membrane fraction. RNA gel blot analysis of various tissues
      and developmental stages indicated thi1 expression was differentially regulated
      in a manner consistent with what is known about thiamine synthesis in plants.
      This is the first report of cDNAs encoding proteins involved in thiamine
      biosynthesis for any plant species.

PMID- 8541507
TI  - Cloning and characterization of differentially expressed genes in imbibed dormant
      and afterripened Avena fatua embryos.
AB  - To analyze the patterns of gene expression associated with seed dormancy in wild
      oat (Avena fatua), we have isolated cDNA clones corresponding to genes that are
      differentially expressed in dormant and afterripened line M73 embryos. Gene
      transcripts of these clones were maintained in embryos of imbibed dormant
      caryopses, but declined rapidly in afterripened embryos after imbibition. GA3
      treatment of dormant caryopses, which breaks dormancy, could lower the transcript
      levels in dormant embryos. When the germination of afterripened caryopses was
      inhibited by high temperature (35 degrees C), the decline in abundance of the
      transcripts in afterripened embryos was arrested. These genes were expressed to
      various degrees in water-stressed, but not in unstressed, 7-day-old seedlings.
      The expression of the genes was also ABA-inducible in afterripened embryos. The
      expression patterns in non-dormant line SH430 wild oat were similar to those of
      afterripened M73. DNA sequence analyses indicated that some of the cDNA clones
      encode LEA (late embryogenesis-abundant) proteins and aldose reductase. The
      significance of the expression of these genes in maintaining seed dormancy or
      longevity is discussed.

PMID- 8541508
TI  - Molecular cloning, characterization and expression analysis of isoforms encoding
      tonoplast-bound proton-translocating inorganic pyrophosphatase in tobacco.
AB  - The tonoplast-bound proton-translocating inorganic pyrophosphatase (V-type PPase)
      and the proton ATPase (V-type ATPase) are electrogenic proton pumps guaranteeing
      the energization of solute transport across the tonoplast. Using an Arabidopsis
      thaliana PCR cDNA fragment corresponding to clone ATAVP3 we have isolated 24 cDNA
      clones encoding tonoplast-bound inorganic pyrophosphatase of tobacco. Based on
      restriction analysis the cDNA clones could be grouped into three different
      classes. The complete nucleotide sequence of one member of each class (TVP5, TVP9
      and TVP31) was determined. The cDNA clones contain an uninterrupted open reading
      frame of 2292 bp (TVP5), 2295 bp (TVP9) and 2298 bp (TVP31) coding for
      polypeptides of 764, 765 and 766 amino acids, respectively. The nucleotide
      sequence of the different clones is highly homologous within the coding region
      (79-89% identity) but differs strongly in the untranslated regions. The
      individual classes are encoded by single- or low-copy genes as judged from
      genomic gel blot experiments using 3'-specific probes. RNA analysis revealed that
      the accumulation of the specific transcripts is differentially regulated during
      leaf development.

PMID- 8541509
TI  - Expression of heat shock factor and heat shock protein 70 genes during maize
      pollen development.
AB  - We have analysed the expression of heat shock protein 70 (HSP70) and heat shock
      factor (HSF) gene during maize pollen development, HSFs being the transcriptional
      activators of hsp genes. In order to eliminate the sporophytic tissues of
      anthers, we have isolated homogeneous cell populations corresponding to five
      stages of maize pollen development from microspores to mature pollen. We show
      that in the absence of heat stress, hsp70 genes are highly expressed late
      bicellular pollen as compared to other stages. HSP70 transcripts are
      significantly accumulated in response to a heat shock at the late microspore
      stage but to a much lower extent than in vegetative tissues. The latest stages of
      pollen development, i.e. mid-tricellular and mature pollen, do not exhibit heat
      induced accumulation of HSP70 transcripts. Therefore, we analysed the expression
      of hsf genes throughout pollen development. We demonstrate that at least three
      hsf genes are expressed in maize and that transcripts corresponding to one hsf
      gene, whose expression is independent of temperature in somatic as well as in
      microgametophytic tissues, are present at similar levels throughout pollen
      development. In addition, we show that the expression of the two other hsf genes
      is heat-inducible in maize vegetative tissues and is not significantly increased
      after heat shock at any stage of pollen development. These results indicate that
      the loss of hsp gene expression at late stages of pollen development is not due
      to a modification of hsf gene expression at the mRNA level and that hsf gene
      expression is differentially regulated in vegetative and microgametophytic
      tissues.

PMID- 8541510
TI  - Genomic organization and evolution of the soybean SB92 satellite sequence.
AB  - Repetitive DNA sequences comprise a large percentage of plant genomes, and their
      characterization provides information about both species and genome evolution. We
      have isolated a recombinant clone containing a highly repeated DNA element (SB92)
      that is homologous to ca. 0.9% of the soybean genome or about 10(5) copies. This
      repeated sequence is tandemly arranged and is found in four or five major genomic
      locations. FISH analysis of metaphase chromosomes suggests that two of these
      locations are centromeric. We have determined the sequence of two cloned repeats
      and performed genomic sequencing to obtain a consensus sequence. The consensus
      repeat size was 92 bp and exhibited an average of 10% nucleotide substitution
      relative to the two cloned repeats. This high level of sequence diversity
      suggests an ancient origin but is inconsistent with the limited phylogenetic
      distribution of SB92, which is found at high copy number only in the annual
      soybeans. It therefore seems likely that this sequence is undergoing very rapid
      evolution.

PMID- 8541511
TI  - Unusual sequences of group 3 LEA mRNA inducible by maturation or drying in
      soybean seeds.
AB  - Two cDNA clones, pGmPM8 and pGmPM10, which correspond to two mRNA species in
      mature or dry soybean seeds, were characterized. The deduced proteins, based on
      DNA sequence analysis, have a molecular mass of 49 and 51 kDa for pGmPM8 and
      pGmPM10, respectively. These two cDNA clones share a high homology with an amino
      acid identity of about 90% between the two deduced proteins. Both proteins appear
      to be extremely hydrophilic except at their N-termini that contain a 29 amino
      acid hydrophobic region at the N-terminus and the sizes of proteins decrease
      after co-incubating with ER membranes. These two proteins contain more than 30
      similar, contiguous repeats of 11 amino acids, which is characteristic of group 3
      LEA proteins. The mRNAs corresponding to pGmPM8 and pGmPM10 were expressed at
      high levels in dried or mature soybean seeds, but not in fresh immature seeds.
      The RNAs were also present in abscisic acid (ABA) treated leaves or cultured
      cells, and in tissues subjected to water stress or low temperatures.

PMID- 8541512
TI  - Uridine, a cell division factor in pea roots.
AB  - Nodulation (root nodule formation) in legume roots is initiated by the induction
      of cell divisions and formation of root nodule primordia in the plant root
      cortex, usually in front of the protoxylem ridges of the central root cylinder.
      We isolated a factor from the central cylinder (stele) of pea roots which
      enhances hormone-induced cell proliferation in root cortex explants at positions
      similar to those of nodule primordia. The factor was identified as uridine.
      Uridine may act as a morphogen in plant roots at picomolar concentrations.

PMID- 8541513
TI  - Cloning of an Arabidopsis thaliana cDNA encoding cystathionine beta-lyase by
      functional complementation in Escherichia coli.
AB  - Cystathionine beta-lyase, the second enzyme involved in the methionine
      biosynthetic pathway in plants, catalyses the synthesis of homocysteine from
      cystathionine. A cDNA encoding cystathionine beta-lyase was cloned from an
      Arabidopsis thaliana expression library by complementation of an Escherichia coli
      mutant deficient in this enzyme. As deduced from the full-length nucleotide
      sequence (1.7 kb), the polypeptide contains 464 amino acids and presents a
      predicted M(r) of 50372. A. thaliana cystathionine beta-lyase exhibits 22%
      sequence identity with the E. coli corresponding enzyme and contains a 70 amino
      acid N-terminal additional sequence compared with the bacterial protein. Since
      the general features of chloroplast transit peptides could be observed in this
      amino-terminal extension, we propose a chloroplast localization for the cDNA
      encoded enzyme. Southern blot analysis suggested that cystathionine beta-lyase is
      encoded by a single copy gene in A. thaliana.

PMID- 8541514
TI  - Control and activity of type-1 serine/threonine protein phosphatase during the
      cell cycle.
AB  - The first part of this discourse will serve as a compendium of selected aspects
      of PP1 activity and control during the cell cycle. The latter sections will focus
      on the mammalian cell cycle dependent activity of PP1 on the negative growth
      regulatory product of the retinoblastoma susceptibility gene, pRB. The purpose
      here is to suggest one possible mechanism to explain how this phosphatase can
      effect cell cycle progression. An argument is made for PP1 playing an indirect
      role in regulating cell cycle progression by modulating the growth suppressive
      activity of pRB.

PMID- 8541515
TI  - The role of protein phosphatase type-2A in the Xenopus cell cycle: initiation of
      the G2/M transition.
AB  - The last several years has seen an explosion in the identification of a
      multiplicity of serine/threonine protein kinases with important functions in
      eukaryotic cell cycle progression. Although the major serine/threonine
      phosphoprotein phosphatases, that must oppose the action of the kinases, have
      been identified and extensively characterized for their involvement in metabolic
      processes, the functions of the phosphatases in cell cycle regulation is less
      well established. This paper focuses on the role of the type-2A protein
      phosphatase (PP2A) in the regulation of the G2/M transition in the Xenopus cell
      cycle. Although a role for PP2A in regulating G2/M has been suggested by studies
      in various systems, it is the relative simplicity of the in-vitro cell cycle
      extracts of Xenopus that has allowed the clearest dissection of the mechanism by
      which PP2A regulates this transition.

PMID- 8541516
TI  - Flicking the switches: phosphorylation of serine/threonine protein phosphatases.
AB  - Signal transduction involves protein phosphorylation and dephosphorylation. To
      produce both substantial and transient changes requires coordinated and
      reciprocal regulation of kinases and phosphatases. One mechanism to accomplish
      this is phosphorylation, and there are now reports of phosphorylation of all the
      major types of protein Ser/Thr phosphatases. Phosphorylation of type-1 and type
      2A phosphatases occurs within characteristic C-terminal sequences and results in
      the loss of phosphatase activity. The phosphatases catalyse intramolecular
      dephosphorylation, with a restoration of activity. This property probably
      accounts for the apparent constitutive activity of phosphatases in cell and
      tissue extracts. Phosphorylation of phosphatases is a way to flick the activity
      off and on in cells during the growth cycle and in response to stimuli.

PMID- 8541517
TI  - Protein phosphatase regulation by endogenous inhibitors.
AB  - Activation and inactivation of protein kinases and phosphatases trigger key
      events in the eukaryotic cell division cycle. Coordinating the opposing actions
      of kinases and phosphatases is also crucial for determining the cellular response
      to physiological stimuli. While regulatory subunits can control the subcellular
      localization and substrate specificity of protein phosphatases, endogenous
      inhibitors represent a mechanism for regulating the overall activity of specific
      enzymes in mammalian tissues. Some phosphatase inhibitors are phosphoproteins.
      Therefore, they communicate changes in kinase activity to selected phosphatases.
      This crosstalk between kinases and phosphatases defines the physiological
      response. Current knowledge on the mode of action of phosphatase inhibitors and
      their potential contributions to cell growth and differentiation are discussed.

PMID- 8541518
TI  - Regulation by tumour antigens defines a role for PP2A in signal transduction.
AB  - Research conducted over the last decade has provided a wealth of new information
      on the molecular mechanisms utilized by DNA tumour viruses. Studies of tumour
      viruses have led to important insights into the functions of viral proteins and
      into the regulation of normal cellular proliferation. DNA tumour viruses can
      stimulate growth factor signaling pathways, alter gene transcription, and
      inactivate growth suppressor proteins. Members of the polyoma and adenovirus
      families express proteins that interact with protein serine/threonine phosphatase
      2A (PP2A). In the case of SV40 virus, this interaction plays an accessory role in
      transformation of most cells, while it is essential for transformation of some
      cell types. The topics discussed in this review include the interactions of these
      viral proteins with PP2A, the effects of these interactions on phosphatase
      activity, and how these interactions alter cellular signal transduction pathways.

PMID- 8541519
TI  - Regulation of gene expression by serine/threonine protein phosphatases.
AB  - The activation of signal transduction pathways by extracellular stimuli, such as
      growth factors or hormones, ultimately results in changes in the expression of
      specific genes. The altered pattern of expression eventually determines the
      resulting cellular consequences, e.g. cell growth, division, or differentiation.
      It has been well established that the reversible phosphorylation of proteins is a
      major regulatory mechanism in these processes. However, while much has been
      learned about the role of kinases, the involvement of protein phosphatases is
      less clear and has only recently begun to be investigated in more detail. This
      review will present some of the new findings that demonstrate a crucial
      regulatory function of serine/threonine protein phosphatases (PPases) in gene
      regulatory processes.

PMID- 8541520
TI  - Role of protein phosphatase 2A in Drosophila development.
AB  - The molecular cloning of protein phosphatase 2A subunits from Drosophila has
      provided insights into the role this enzyme plays in developmental processes and
      in cell cycle regulation. The trimeric holoenzyme containing the catalytic, 65
      kDa and 55-kDa regulatory subunits appears to be preferentially expressed in
      proliferative organs such as the gonads, in the developing nervous system and in
      early syncytial embryos. Analysis of mutant flies affected in the expression of
      the 55-kDa regulatory subunit suggests that the holoenzyme containing this
      subunit plays a pivotal role in cell cycle regulation and cell fate
      determination. The severity of the mutant phenotype correlates with a decrease in
      55-kDa subunit protein levels and reduced protein phosphatase activity towards
      p34cdc2 phosphorylated proteins. The data support the idea that the 'variable'
      subunits of protein phosphatase 2A holoenzymes play a critical role in directing
      substrate specificity.

PMID- 8541521
TI  - Impedance of a fibrin clot in a cylindrical tube: relation to clot permeability
      and viscoelasticity.
AB  - By use of an impedance to quantify the pressure-to-flow relation for a clot
      filled tube, a simple model is developed that encompasses both viscoelastic and
      porous properties of the clot. Measurements over a range of frequencies are used
      to separate the role of clot permeability from clot matrix elasticity. The
      theoretical impedance model consists of a series resistance and capacitance
      (representing structural flow) in parallel with a resistance (representing
      permeating flow). The viscoelasticity of the matrix, permeability and effective
      pore size are related to these three impedance elements. The validity of the
      model has been verified for a range of vessel sizes approximating small arteries
      (1 to 3 mm in diameter). The presence of dextran T40 in clotted fibrinogen
      solutions changes the clot impedance by increasing clot permeability and
      decreasing clot viscoelasticity. Because the flow contains two components, the
      behavior of a clot in vivo under pulsatile pressure cannot be predicted from the
      viscoelastic properties obtained from non-tube flow instruments nor from steady
      flow permeation measurements; a combination of the two as provided by oscillatory
      tube-flow measurements is required.

PMID- 8541522
TI  - Rheological approach to the analysis of blood coagulation in endothelial cell
      coated tubes: activation of the intrinsic reaction on the erythrocyte surface.
AB  - Coagulation of blood in cultured endothelial cell-coated tubes was examined using
      a rheological technique. Coagulation of recalcified, platelet-free plasma in
      contact with an endothelial cell monolayer did not occur within the experimental
      time period (more than 150 min). The endothelial cell surface did not activate
      the intrinsic coagulation reaction or the extrinsic coagulation reaction
      initiated by tissue factor. The time of onset of coagulation in platelet-free
      plasma supplemented with erythrocytes was nearly the same as that of whole blood
      (31.2 +/- 5.5 min), which was shorter than that for platelet-rich plasma (54.3 +/
      14.3 min) and platelet-free plasma supplemented with granulocytes (58.3 +/- 6.3
      min). In factor VII-, XI- or XII-deficient, platelet-free plasma supplemented
      with erythrocytes, the time of onset of coagulation was about 30 min. The
      coagulation of factor IX-deficient, platelet-free plasma supplemented with
      erythrocytes, however, did not occur within the experimental time period. These
      data suggest that activation of factor IX on the erythrocyte surface is capable
      of activating the intrinsic coagulation system.

PMID- 8541523
TI  - Effect of hematocrit on adenosine diphosphate-induced aggregation of human
      platelets in tube flow.
AB  - Both chemical and physical effects of red cells are known to play a role in the
      adenosine diphosphate (ADP)-induced aggregation of human platelets in sheared
      blood. Using a previously described double infusion technique (Bell et al.,
      1989a), we studied the effect of increasing hematocrit from 10 to 60% on the rate
      and extent of platelet aggregation with 0.2 microM ADP in citrated whole blood
      undergoing tube flow. Blood and agonist were rapidly mixed in a small chamber and
      the suspensions flowed through lengths of 1.19 mm-diameter polyethylene tubing at
      mean transit times <t> from 0.2 to 42.8 s at a mean tube shear rate <G> = 335 s
      1. Effluent was collected into 0.5% glutaraldehyde, the red cells removed by
      centrifugation through Percoll, and all single platelets and aggregates in the
      volume range 1-10(5) microns3 counted and sized using an aperture impedance
      counter. Both the initial rate (over the first 8.6 s) and the extent of
      aggregation with time increased with increasing mean hematocrit up to 35.8%,
      being significantly greater than in citrated plasma (cPRP). However, at 61.5%
      hematocrit, the extent of aggregation decreased markedly to a level close to that
      in cPRP. We also studied the effect of washed red cells at 39% hematocrit on the
      aggregation of washed platelets in Tyrodes-albumin fibrinogen-free suspensions.
      It had previously been shown that, at <G> > or = 335 s-1, washed platelets in
      platelet-rich Tyrodes (PRT) aggregated with 0.7 microM ADP. We found that red
      cells markedly increased the extent of aggregation from that in PRT, and promoted
      the formation of large aggregates, absent in PRT. Spontaneous aggregation in
      whole blood or washed cell suspensions in the absence of added ADP at <t> = 42.8
      s was < 10% of that in the presence of ADP. The results indicate that a physical
      effect of red cells, likely manifested as an increase in the efficiency of
      aggregate formation (Goldsmith et al., 1995), plays an important role at low and
      normal hematocrits; however, at high hematocrits, particle crowding impedes the
      formation of aggregates.

PMID- 8541524
TI  - Microscopic photometric quantification of stiffness and relaxation time of red
      blood cells in a flow chamber.
AB  - The Microscopic Photometric Monolayer Technique provides a tool to measure red
      blood cell (RBC) stiffness (resistance to elongation) and relaxation time. It
      combines many of the advantages of flow channel studies of point-attached RBCs
      with the simplicity, sensitivity and accuracy of photometric light transmission
      measurement. This technique allows the study of the effects of physicochemical
      factors on the elongation and relaxation time of the same cells within an average
      of four to five thousand cells adhered as a monolayer to glass. Further, the time
      course of physicochemical effects on cell membrane and wash-in/wash-out kinetics
      of interactions can be followed. An automated version of this technique was
      developed. A dense monolayer of point-attached RBCs was prepared at the bottom of
      a flow-chamber. A steady-state flow, with stepwise increases of flow rate,
      induced the RBC elongation. The light transmission perpendicular through the
      monolayer plane was measured photometrically. Photomicrographs compared with
      photometric results showed that the flow-induced bending and curvature change of
      RBC membrane was associated with the increase of light transmission. There was a
      linear correlation between the photometric index of elongation and the elongation
      taken from photomicrographs for shear stresses up to 0.75 Pa. A stiffness
      parameter, S (in Pa), was defined as the ratio of shear stress and elongation at
      a shear stress of 0.25 Pa. Following a sudden flow stoppage, the RBCs returned to
      their resting shape and the RBC relaxation time was measured. The stiffness
      relaxation time product, V (in mPas), was calculated to provide an estimate of
      viscosity. Diamide treatment, known to stiffen RBCs, did result in dose-dependent
      decreases of elongation and relaxation time. With increasing temperature, the
      relaxation time decreased at a rate of -2.96 ms/K; the stiffness increased
      significantly at a rate of 0.0038 Pa/K, and the stiffness-relaxation time product
      decreased with -2.95 mPas/K, reflecting an inverse relationship between RBC
      viscosity and temperature. Using the automated version of this technique (Elias-c
      ) to test RBCs of 36 healthy subjects, we found the inter-individual coefficients
      of variation to be 8.6% for stiffness, 7.9% for relaxation time and 12.4% for
      stiffness-relaxation time product.

PMID- 8541525
TI  - Electrochemical analysis of blood cell/substrate interactions under flow
      conditions.
AB  - Interactions of blood cells (RBCs) with a microelectrode of 50 microns diameter
      have been examined under flow conditions using impedance measurements at high
      frequencies. At such frequencies, the electrolyte resistance (Re) is assimilated
      to the real part of impedance, and interactions are associated with transient
      fluctuations of Re. Sedimentation experiments suggest that one erythrocyte
      contributes to a 1.1% Re increase. Effects of wall shear rate (from 25 to 140 s
      1) and RBC concentration (from 8.4 x 10(5) to 2.7 x 10(6) cells/ml) have been
      investigated; the number of interactions rapidly decreases with wall shear rate.
      Event frequency is proportional to RBC concentration ranging from 3.1 x 10(6)
      cells/ml to 1.3 x 10(7) cells/ml. At high concentrations of RBCs, some transient
      events overlap. Videotaped images help to determine how many RBCs interact with
      the microelectrode at the same time on separate surface areas. Under flow
      conditions, the contribution of one RBC on the Re increase is similar to the
      mathematical value obtained by sedimentation and decreases slightly with wall
      shear rate.

PMID- 8541526
TI  - The molecular dissection of Fc gamma receptor mediated phagocytosis.
AB  - Because hematopoietic cells express multiple Fc gamma receptor isoforms, the role
      of the individual Fc gamma receptors in phagocytosis has been difficult to
      define. Transfection of Fc gamma receptors into COS-1 cells, which lack
      endogeneous Fc gamma receptors but have phagocytic potential, has proved valuable
      for the study of individual Fc gamma receptor function. Using this model system,
      we have established that a single class of human Fc gamma receptor mediates
      phagocytosis in the absence of other Fc receptors and that isoforms from each Fc
      gamma receptor class mediate phagocytosis, although the requirements for
      phagocytosis differ. In investigating the relationship between structure and
      function for Fc gamma receptor mediated phagocytosis, the importance of the
      cytoplasmic tyrosines of the receptor or its associated gamma chain has been
      established. For example, two cytoplasmic YXXL sequences, in a configuration
      similar to the conserved tyrosine-containing motif found in Ig gene family
      receptors, are important for phagocytosis by the human Fc gamma receptor, Fc
      gamma RIIA. Fc gamma RI and Fc gamma RIIIA do not possess cytoplasmic tyrosines
      but transmit a phagocytic signal through interaction with an associated gamma
      subunit that contains two YXXL sequences in a conserved motif required for
      phagocytosis. The human Fc gamma RII isoforms Fc gamma RIIB1 and Fc gamma RIIB2
      do not induce phagocytosis and have only a single YXXL sequence. Cross-linking
      the phagocytic Fc gamma receptors induces tyrosine phosphorylation of either Fc
      gamma RIIA or the gamma chain, and treatment with tyrosine kinase inhibitors
      reduces both phagocytosis and phosphorylation of the receptor tyrosine residues.
      Activation of protein tyrosine kinases follows Fc gamma receptor engagement of
      IgG-coated cells. The data indicate that coexpression of the protein tyrosine
      kinase Syk, which is associated with the gamma chain in monocytes/macrophages, is
      important for phagocytosis mediated by Fc gamma RI and Fc gamma RIIIA.
      Furthermore, phosphatidylinositol-3 kinase is required for phagocytosis mediated
      by Fc gamma RIIA as well as for phagocytosis mediated by Fc gamma RI/gamma and Rc
      gamma RIIIA/gamma.

PMID- 8541527
TI  - BB-10010: an active variant of human macrophage inflammatory protein-1 alpha with
      improved pharmaceutical properties.
AB  - The stem cell inhibitor, macrophage inflammatory protein-1 alpha (MIP-1 alpha) or
      LD78, protects multipotent hematopoietic progenitors in murine models from the
      cytotoxic effects of chemotherapy. Clinical use of human MIP-1 alpha during
      chemotherapy could therefore lead to faster hematologic recovery and may allow
      dose intensification. We have also shown that human MIP-1 alpha causes the rapid
      mobilization of hematopoietic cells, suggesting an additional clinical use in
      peripheral blood stem cell transplantation. However, the clinical evaluation of
      human MIP-1 alpha is complicated by its tendency to associate and form high
      molecular weight polymers. We have produced a variant of rhMIP-1 alpha, BB-10010,
      carrying a single amino acid substitution of Asp26 > Ala, with a reduced tendency
      to form large polymers at physiologic pH and ionic strength. This greatly
      increases its solubility, facilitating its production and clinical formulation.
      We confirmed the potency of BB-10010 as a human MIP-1 alpha-like agonist in
      receptor binding, calcium mobilization, inhibition of colony formation, and
      thymidine suicide assays. The myeloprotective activity of BB-10010 was shown in a
      murine model of repeated chemotherapy using hydroxyurea. BB-10010 is therefore an
      ideal variant with which to evaluate the therapeutic potential of recombinant
      human MIP-1 alpha.

PMID- 8541528
TI  - Granulocyte colony-stimulating factor rapidly activates a distinct STAT-like
      protein in normal myeloid cells.
AB  - Binding of granulocyte colony-stimulating factor (G-CSF) to normal myeloid cells
      activates the protein tyrosine kinases Lyn and Syk and results in the immediate
      early upregulation of G-CSF receptor (R) mRNA. In our studies of the signaling
      pathways activated by G-CSF that are coupled to proliferation and differentiation
      of myeloid cells, we examined whether G-CSF activated a latent transcription
      factor belonging to the STAT protein family. Electrophoretic mobility shift
      assays (EMSAs) of nuclear extracts from G-CSF-stimulated human myeloid cells
      showed the rapid activation of a DNA-binding protein that bound to the high
      affinity serum-inducible element (hSIE) and migrated with mobility similar to
      serum inducible factor (SIF)-A (Stat3 homodimer). The G-CSF-stimulated SIF-A
      complex (G-SIF-A) did not bind to duplex oligonucleotides used to purify and
      characterize other Stat proteins (Stat1-6). In addition, antibodies raised
      against Stat1-6 failed to supershift the G-SIF-A complex or interfere with its
      formation. Based on its binding to the hSIE and lack of antigenic cross
      reactivity with other known STAT proteins that bind to this element, it is likely
      that G-SIF-A is composed of a distinct member of the STAT protein family. EMSAs
      of whole-cell extracts prepared from cell lines containing full-length and
      truncated mutants of the G-CSFR showed that activation of G-SIF-A did not
      correlate with proliferation; rather, optimal activation requires the distal half
      of the cytosolic domain of the G-CSFR that is essential for differentiation.
      Activation of G-SIF-A, therefore, may be an early G-CSFR-coupled event that is
      critical for myeloid maturation.

PMID- 8541529
TI  - Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand-1.
AB  - Leukocyte rolling, an early and important step in the inflammatory response, is
      mediated by the selectin family of adhesion molecules. The selectins bind with
      low affinity to sialylated and fucosylated glycans such as sialyl Lewisx (sLex),
      but bind with high affinity to only a few specific glycoproteins on cell
      surfaces. One such glycoprotein is P-selectin glycoprotein ligand-1 (PSGL-1). The
      relative contributions of low- and high-affinity ligands to leukocyte rolling in
      vivo are unknown. We show here that a monoclonal antibody to PSGL-1 (PL1)
      dramatically reduces rolling of human polymorphonuclear neutrophils (PMN) and
      promyelocytic HL-60 cells in venules of acutely exteriorized rat mesentery.
      Control PMN and HL-60 cell rolling flux fractions were 39% +/- 3% and 33% +/- 5%,
      which were reduced by PL1 to 7% +/- 2% and 6% +/- 2%, respectively. Similar
      reductions were seen with F(ab) fragments of PL1. PL1-treated PMN rolled at
      significantly higher mean velocities than untreated PMN owing to intermittent
      rather that continuous interactions. These findings show that interaction of P
      selectin with PSGL-1 is required for rolling of myeloid cells in mesenteric
      venules at physiologic shear stress in vivo.

PMID- 8541530
TI  - Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes
      donor T lymphocytes toward type-2 cytokine production and reduces severity of
      experimental graft-versus-host disease.
AB  - The incidence and severity of acute graft-versus-host disease (GVHD) after
      allogeneic transplantation using peripheral blood progenitor cells mobilized by
      granulocyte colony-stimulating factor (G-CSF) appear to be no worse than those
      after bone marrow transplantation, despite the presence of large numbers of T
      cells in the donor infusion. Experimental studies have shown that type-1 T cells
      (secreting interleukin-2 [IL-2] and interferon-gamma) mediate acute GVHD, whereas
      type-2 T cells (secreting IL-4 and IL-10) can prevent acute GVHD. We tested the
      hypothesis that G-CSF modulates T-cell function toward a type-2 response and thus
      reduces the severity of acute GVHD. B6 mice were injected with G-CSF or diluent
      for 4 days, and their splenic T cells were stimulated in vitro with alloantigen
      or mitogen in the absence of G-CSF. T cells from G-CSF-treated mice showed a
      significant increase in IL-4 production, with a simultaneous decrease in IL-2 and
      interferon-gamma production in response to both stimuli. We also examined the
      effect of G-CSF pretreatment of donors in a GVHD model (B6-->B6D2F1). Survival
      was significantly improved in recipients of G-CSF-treated donors. Concanavalin-A
      induced cytokine production at day 13 after transplantation also showed an
      increase in IL-4 along with a decrease in IL-2 and IFN-gamma production by
      splenocytes from recipients of G-CSF-treated bone marrow and T cells. These data
      show that pretreatment of donors with G-CSF polarizes donor T cells toward the
      production of type-2 cytokines, which is associated with reduced type-1 cytokine
      production and reduced severity of acute GVHD.

PMID- 8541531
TI  - A human monoclonal antibody specific for the leucine-33 (P1A1, HPA-1a) form of
      platelet glycoprotein IIIa from a V gene phage display library.
AB  - IgG alloantibodies to polymorphic platelet glycoproteins (GPs) are known to be
      responsible for severe thrombocytopenia in the neonate and after transfusion.
      Platelet GPIIIa can have either a leucine or a proline at residue 33. The most
      immunogenic platelet alloantigen in thrombocytopenia is the leucine 33 form of
      GPIIIa. Here, we have generated human monoclonal antibody fragments that are
      specific for the leucine and not the proline form of GPIIIa and can inhibit the
      binding of polyclonal human IgG alloantibodies to GPIIIa leucine 33 on platelets.
      The antibody fragments were selected from a library of single chain Fv fragments
      displayed on the surface of filamentous phage. The VH gene repertoire was derived
      from the peripheral blood lymphocytes of an alloimmunized individual and
      recombined with a VL gene repertoire from a nonimmune source. Antibodies such as
      these, which are able to distinguish between two variant forms of a native
      antigen and which have been unobtainable by conventional hybridoma technology,
      have both diagnostic and potential therapeutic applications.

PMID- 8541532
TI  - Optimizing dose and scheduling of filgrastim (granulocyte colony-stimulating
      factor) for mobilization and collection of peripheral blood progenitor cells in
      normal volunteers.
AB  - To define an optimal regimen for mobilizing and collecting peripheral blood
      progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the
      kinetics of mobilization by filgrastim (recombinant met-human granulocyte colony
      stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected
      subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10
      micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent
      a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte
      macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5
      days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and
      6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of
      blood in the three dose cohorts overlapped on each study day. However, on the
      peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort
      than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not
      significantly influenced by volunteer age or sex. Leukapheresis products obtained
      at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x
      10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers
      receiving lower doses of filgrastim contained a median GM-CFC number of 36 x
      10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells
      per milliliter of blood on the day of leukapheresis predicted the total yield of
      PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC
      requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC
      transplantation), all seven leukapheresis products obtained at the 10
      micrograms/kg/d dose level were potentially sufficient for allogeneic
      transplantation purposes. We conclude that in normal donors, filgrastim 10
      micrograms/kg/d for 5 days with a single leukapheresis on the following day is a
      highly effective regimen for PBPC mobilization and collection. Further studies
      are required to determine whether PBPC collected with this regimen reliably
      produce rapid and sustained engraftment in allogeneic recipients.

PMID- 8541533
TI  - Recombinant human erythropoietin in the anemia associated with multiple myeloma
      or non-Hodgkin's lymphoma: dose finding and identification of predictors of
      response.
AB  - Previous phase I-II clinical trials have shown that recombinant human
      erythropoietin (rHuEpo) can ameliorate anemia in a portion of patients with
      multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Therefore, we performed a
      randomized controlled multicenter study to define the optimal initial dosage and
      to identify predictors of response to rHuEpo. A total of 146 patients who had
      hemoglobin (Hb) levels < or = 11 g/dL and who had no need for transfusion at the
      time of enrollment entered this trial. Patients were randomized to receive 1,000
      U (n = 31), 2,000 U (n = 29), 5,000 U (n = 31), or 10,000 U (n = 26) of rHuEpo
      daily subcutaneously for 8 weeks or to receive no therapy (n = 29). Of the
      patients, 84 suffered from MM and 62 from low- to intermediate-grade NHL,
      including chronic lymphocytic leukemia; 116 of 146 (79%) received chemotherapy
      during the study. The mean baseline Hb level was 9.4 +/- 1.0 g/dL. The median
      serum Epo level was 32 mU/mL, and endogenous Epo production was found to be
      defective in 77% of the patients, as judged by a value for the ratio of observed
      to-predicted serum Epo levels (O/P ratio) of < or = 0.9. An intention-to-treat
      analysis was performed to evaluate treatment efficacy. The median average
      increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 (P =
      .57), 0.22 (P = .05), 0.43 (P = .01), and 0.58 (P = .0001) g/dL in the 1,000 U,
      2,000 U, 5,000 U, and 10,000 U groups, respectively (P values versus control).
      The probability of response (delta Hb > or = 2 g/dL) increased steadily and,
      after 8 weeks, reached 31% (2,000 U), 61% (5,000 U), and 62% (10,000 U),
      respectively. Regression analysis using Cox's proportional hazard model and
      classification and regression tree analysis showed that serum Epo levels and the
      O/P ratio were the most important factors predicting response in patients
      receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting
      with Epo levels inappropriately low for the degree of anemia responded to rHuEpo,
      whereas only one quarter of those with adequate Epo levels did so. Classification
      and regression tree analysis also showed that doses of 2,000 U daily were
      effective in patients with an average platelet count greater than 150 x 10(9)/L.
      About 50% of these patients are expected to respond to rHuEpo. Thus, rHuEpo was
      safe and effective in ameliorating the anemia of MM and NHL patients who showed
      defective endogenous Epo production. From a practical point of view, we conclude
      that the decision to use rHuEpo in an individual anemic patient with MM or NHL
      should be based on serum Epo levels, whereas the choice of the initial dosage
      should be based on residual marrow function.

PMID- 8541534
TI  - CD34+ endothelial cell lines derived from murine yolk sac induce the
      proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors.
AB  - Embryonic hematopoiesis is initiated in part in the blood islands of the yolk
      sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a
      mucin-like cell surface glycoprotein that is expressed by hematopoietic
      progenitors and all endothelial cells of the adult and embryo, is also found on a
      subset of luminal hematopoietic-like cells in the yolk sac blood islands as well
      as on the vascular endothelium lining these early hematopoietic locations. We
      show here that, as in all other hematopoietic sites thus far examined,
      immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the
      vast majority of erythroid and myeloid progenitor cell colony forming activity.
      To examine the developmental interactions between these CD34+ hematopoietic
      progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have
      immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using
      CD34 antiserum and produced cell lines by transformation with a retrovirus
      expressing the polyoma middle T antigen. Analysis of these cell lines for CD34,
      von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in
      Matrigel indicates that they appear to be endothelial cells, consistent with
      their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells
      on these endothelial cell lines results in up to a 60-fold increase in total
      hematopoietic cell number after approximately 8 days. Analysis of these expanded
      hematopoietic cells showed that the majority were of the monocyte/macrophage
      lineage. In addition, examination of the cultures showed the rapid formation of
      numerous cobblestone areas, a previously described morphologic entity thought to
      be representative of early pluripotential stem cells. Scrutiny of the ability of
      these endothelial cell lines to expand committed progenitor cells showed up to a
      sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days
      in culture, consistent with the notion that these embryonic endothelial cells
      mediate the expansion of these precursor cells. Polymerase chain reaction
      analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell
      factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and
      interleukin-6 (IL-6), whereas there is a generally low or not measurable
      production of granulocyte colony-stimulating factor, granulocyte-macrophage
      colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1,
      erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from
      these cocultures can be modified to include an erythroid population by the
      addition of exogenous erythropoietin. These data suggest that endothelial cell
      lines derived form the yolk sac provide an appropriate hematopoietic environment
      for the expansion and differentiation of yolk sac progenitor cells into at least
      the myeloid and erythroid lineages.

PMID- 8541535
TI  - Plastic-adherent progenitor cells in mobilized peripheral blood progenitor cell
      collections.
AB  - The use of peripheral blood progenitor cells (PBPC) to reconstitute hematopoiesis
      after high-dose chemoradiotherapy is now commonplace in the treatment of
      malignancies. Attempts to characterize these cells have concentrated primarily on
      their phenotype and their content of clonogenic colony-forming cells (CFC). We
      have used a plastic-adherent delta (P delta) assay system to evaluate the
      quantity and quality of more primitive cells in addition to the conventional
      measurements of CFC and CD34-positive cells. The leukapheresis products from 20
      patients mobilized using cyclophosphamide (Cy) and granulocyte colony-stimulating
      factor (G-CSF) were examined for progenitor cell content. The mean number of
      mononuclear cells (MNC), colony-forming units-granulocyte/macrophage (CFU-GM),
      and CD34-positive cells from two leukaphereses per patients were 7.9 x 10(8)/kg,
      47.3 x 10(4)/kg, and 10.5 x 10(6)/kg, respectively. The mean number of P delta
      progenitors was 9.3 x 10(4)/kg. Limiting dilution analyses showed the frequency
      of P delta progenitors in PBPC to be between 1 and 5.3 per 10(5) MNC and that
      each P delta progenitor has the proliferative capability to generate an overall
      mean of 4.5 CFU-GM. Of the 20 patients, 16 underwent autografting with PBPC
      alone. Fifteen patients engrafted neutrophils and platelets within 16 days. One
      patient had delayed engraftment associated with inadequate etoposide clearance.
      Statistical analysis showed a strong correlation between numbers of CFU-GM and
      CD34 positivity. The numbers of plastic-adherent P delta progenitor cells did not
      correlate with CFU-GM or CD34-positive cells. We conclude that the plastic
      adherent P delta progenitor cell assay is capable of measuring primitive
      hematopoietic cells and that it may be useful for the investigation of primitive
      progenitors in PBPC harvests.

PMID- 8541536
TI  - Characterization of hematopoietic progenitors from human yolk sacs and embryos.
AB  - Hematopoiesis first arises in the extraembryonic yolk sac, and it is generally
      believed that yolk sac-derived stem cells migrate and seed the fetal liver at
      approximately week 6 of development in humans. Recently, the identification at
      day 8.5 to 9 of multipotential stem cells in intraembryonic sites different from
      the liver suggests that the establishment of hematopoiesis might be more complex
      than initially believed. In an attempt to understand initial steps of
      hematopoiesis during human ontogeny, we characterized clonogenic myeloid
      progenitor cells in human yolk sacs and corresponding embryos at 25 to 50 days of
      development. Most erythroid colonies derived from the yolk sacs differed from
      adult marrow-derived progenitors in that they also contained cells of the
      granulomacrophagic lineage, suggesting that they were pluripotent and exhibited a
      different response to cytokines. Furthermore, a subclass of nonerythroid
      progenitors generated very large granulomacrophagic colonies, some of which
      generated secondary erythroid colonies on replating. Analysis of the distribution
      of progenitors revealed that in contrast to erythroid progenitors, whose numbers
      were equally distributed between the yolk sac and the embryo, 80% of the
      nonerythroid progenitors were found in the embryo at stages II and III.
      Interestingly, a high proportion of nonerythroid progenitors (including high
      proliferative potential cells) was present in colony assays initiated with cells
      remaining after the liver has been removed. These findings were validated in
      colony assays established with CD34+ cells purified from extraembryonic yolk sacs
      and intraembryonic tissues. Increased knowledge about the biology of
      hematopoietic stem cells early in life may help to further understanding of the
      mechanisms associated with the restriction in proliferative and differentiative
      potential observed in the adult hematopoietic stem cell compartment.

PMID- 8541537
TI  - Pegylated megakaryocyte growth and development factor abrogates the lethal
      thrombocytopenia associated with carboplatin and irradiation in mice.
AB  - Megakaryocyte growth and development factor (MGDF) is a potent inducer of
      megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear
      to be lineage-selective, making this cytokine an ideal candidate for use in
      alleviating clinically relevant thrombocytopenias. This report describes a murine
      model of life-threatening thrombocytopenia that results from the combination
      treatment of carboplatin and sublethal irradiation. Mortality of this regimen is
      94% and is associated with widespread internal bleeding. The daily administration
      of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality
      (to < 15%) and ameliorated the depth and duration of thrombocytopenia. The
      severity of leucopenia and anemia was also reduced, although it was not clear
      whether these effects were direct. Platelets generated in response to PEG-rMGDF
      were morphologically indistinguishable from normal platelets. PEG-rMGDF
      administered in combination with murine granulocyte colony-stimulating factor
      completely prevented mortality and further reduced leukopenia and
      thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to
      treat iatrogenic thrombocytopenias.

PMID- 8541538
TI  - Corticosteroid alteration of carboplatin-induced hematopoietic toxicity in a
      murine model.
AB  - Corticosteroids exhibit extensive hematopoietic effects both in vitro and in
      vivo. Some of the previously studied effects suggested that corticosteroids may
      alter hematopoietic toxicity of chemotherapeutic agents. In this study, we
      examined (1) the optimum dose and schedule of cortisone acetate (CA) to reduce
      hematopoietic toxicity of carboplatin (CB) and (2) possible mechanisms involved
      in this protective effect. CA given subcutaneously at 0.5 mg/d per mouse for 7
      days before CB reduced CB-induced mortality due to neutropenia from 88% in
      controls to 14% in CA-treated mice (P < .05). Lower CA doses were not effective.
      Three days of pretreatment (but not 1 day) was as effective as 7 days. CA given
      after CB had no effect on mortality. Pharmacokinetic studies of CA at 0.5 mg per
      mouse demonstrated blood levels of cortisol achievable in patients (peak level,
      82 micrograms/dL). CA treatment markedly reduced spleen cell number and colony
      forming units-granulocyte/macrophage (CFU-GM) as well as bone marrow CFU-GM. Bone
      marrow CFU-GM removed from CA-treated mice demonstrated increased resistance to
      platinum and increased resistance to high specific activity 3H-thymidine. These
      findings suggest that treatment of mice with CA induces cellular resistance of
      hematopoietic precursors to platinum and, thus, reduces CB hematotoxicity. CA or
      other corticosteroids may be useful in reducing clinical toxicity of CB.

PMID- 8541539
TI  - The protein tyrosine kinase JAK2 is activated in neutrophils from patients with
      severe congenital neutropenia.
AB  - Severe congenital neutropenia (SCN; or Kostmann syndrome) is an autosomal
      recessive disorder characterized by a maturation arrest of myelopoiesis at the
      level of promyelocytes. Myeloid precursor cells from patients with SCN require
      pharmacological dosages of recombinant human granulocyte colony-stimulating
      factor (r-metHuG-CSF; Filgrastim; Amgen, Thousand Oaks, CA) to differentiate to
      normal neutrophils. Thus, it is hypothesized that the underlying defect
      responsible for SCN is based on an abnormal G-CSF-induced signal transduction
      pathway. Because JAK2, a nonreceptor tyrosine kinase, is involved in the
      signaling pathway of G-CSF, we examined the expression and activity of JAK2 in
      neutrophils from SCN patients during r-metHuG-CSF treatment. The
      immunoprecipitated JAK2 protein showed increased tyrosine phosphorylation in
      neutrophils from SCN patients as compared with that in neutrophils from healthy
      donors, suggesting that this kinase is activated. In vitro kinase assays of
      immunoprecipitated JAK2 confirmed that neutrophils from SCN patients show an
      increased autophosphorylation of JAK2 in comparison with that of neutrophils from
      healthy volunteers. These findings suggest that JAK2 is activated in SCN
      patients.

PMID- 8541540
TI  - Metalloproteinase inhibition and erythroid potentiation are independent
      activities of tissue inhibitor of metalloproteinases-1.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1), the major physiological matrix
      metalloproteinase inhibitor and a potent antimetastatic factor, also stimulates
      the growth of erythroid progenitors (erythroid-potentiating activity). We
      analyzed the relationship between the growth factor activity and protease
      inhibition by preparing purified TIMP-1 "knockout" proteins lacking in vitro
      antiproteolytic activity. The growth-stimulatory effect of these N-terminal TIMP
      1 point mutants, as tested in an in vitro assay using erythroid precursors
      (erythroid burst-forming units) was equal to that of unmutated TIMP-1. A fully
      antiproteolytic C-terminal TIMP-1 truncation also stimulated growth in the
      erythroid burst-forming unit assay. The results indicate that the influence of
      TIMP-1 on erythroid precursor growth is independent of its ability to inhibit
      metalloproteinases. TIMP-1 is analogous to proteins that have both proteolytic
      and growth factor activity, such as plasmin, thrombin, and urokinase. However,
      TIMP-1 is novel in this regard because it is a metalloproteinase inhibitor. We
      show that the antiproteolytic and growth factor activities of the TIMP-1 molecule
      are physically and functionally distinct.

PMID- 8541541
TI  - Mofarotene (Ro 40-8757) inhibits hematopoiesis in vitro by preventing maturation
      from primitive progenitor cells.
AB  - The effect of the arotinoid mofarotene (Ro 40-8757; 4-[2-[p-[(E)- 2(5,6,7,8
      tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)- propenyl]phenoxy]ethyl]morpholine) on
      stromal cell-mediated hematopoiesis was examined in murine long-term bone marrow
      cultures. Whether added at week 2 to regenerating cultures or at week 4 to
      plateau-phase cultures, mofarotene strongly inhibited total cell production in a
      dose-dependent manner. Progenitor cell production was also inhibited, but to a
      lesser extent. When added at the initiation of culture, 1 mumol/L mofarotene did
      not affect formation of the adherent layer, but production of total nucleated
      cells and progenitors was inhibited over the next 10 weeks by 95% and 96%,
      respectively. However, after mofarotene treatment ceased, progenitor cell levels
      began increasing immediately, and cell production reached plateau levels
      comparable with those of control cultures within 4 weeks. Hematopoiesis was
      maintained for 14 more weeks, indicating that long-term culture-initiating cells
      survived the treatment. Assays of spleen colony-forming units (CFU-S) in the
      adherent layers showed an enrichment of day-13 CFU-S relative to the more mature
      day-9 CFU-S. Mofarotene did not inhibit colony formation by bone marrow cells
      stimulated by exogenous growth factors and did not decrease production of growth
      factors by stromal cells in the cultures, as determined by functional assays and
      by mRNA levels. These results suggest that mofarotene blocks differentiation of
      very primitive progenitors, inhibiting production of more mature hematopoietic
      elements.

PMID- 8541542
TI  - Negative regulation of early T lymphopoiesis by interleukin-3 and interleukin-1
      alpha.
AB  - We recently developed a two-step clonal cell culture system for murine
      lymphohematopoietic progenitors that are capable of producing myeloid and B
      lymphoid progenies and characterized their cytokine requirements. We subsequently
      observed that addition of interleukin-3 (IL-3) or IL-1 alpha to permissive
      cytokine combinations in primary culture abrogates the B-lymphoid potential but
      not the myeloid potential of the lymphohematopoietic progenitors. We now describe
      a similar negative regulation of the T-cell potential of the lymphohematopoietic
      progenitors. Lin- Ly-6A/E+ marrow cells from 5-fluorouracil-treated mice were
      plated individually by micromanipulation in methylcellulose culture with steel
      factor (SF) and IL-11 for 8 days. The resulting colonies were tested for myeloid
      potential by reculturing part of each colony in secondary myeloid suspension
      culture. Remainders of individual primary colonies were injected intravenously
      into scid mice for determination of T- and B-lymphoid potentials. Approximately
      10% of the progenitors that differentiated along myeloid lineages in culture
      reconstituted T- and B-cell compartments in scid mice. However, when scid mice
      were injected with colonies pooled from cultures containing steel factor, IL-11,
      and either IL-3 or IL-1 alpha, there was no reconstitution of thymocytes or
      spleen T cells. These results suggest negative regulatory roles for IL-3 and IL-1
      alpha in the early stages of T lymphopoiesis.

PMID- 8541543
TI  - Megakaryocyte growth and development factor and interleukin-3 induce patterns of
      protein-tyrosine phosphorylation that correlate with dominant differentiation
      over proliferation of mpl-transfected 32D cells.
AB  - Recently, the ligand for c-mpl, a member of the family of cytokine receptors, was
      cloned and found to be a physiologic regulator of platelet homeostasis. We report
      that megakaryocyte growth and development factor (MGDF, thrombopoietin [TPO], c
      mpl ligand ) induces differentiation in a majority of mpl-transfected 32D cells,
      while interleukin (IL)-3 is exclusively mitogenic in this system. MGDF
      differentiation, as measured by decreased proliferation, changes in cellular
      morphology, increased adherence, and downregulation of very late antigen (VLA)-4,
      is dominant over IL-3 proliferation. MGDF induces tyrosine-phosphorylation of
      mpl, JAK2, SHC, SHPTP-1 (HCP, motheaten) and SHPTP-2 (Syp, PTP-1D) within 30
      seconds of stimulation, as well as of vav and MAPK with slightly delayed
      kinetics. A fraction of mpl and JAK2 is preassociated, and the stoichiometry of
      this complex is unaltered by cytokine stimulation. After MGDF stimulation, we
      detect interactions among SHC, grb2, SHPTP-1, SHPTP-2, and the mpl/JAK2 complex.
      IL-3 induces phosphorylation of the above proteins with the exception of mpl and
      also causes weak JAK1 phosphorylation. Although similar in composition, the MGDF-
      and IL-3-induced complexes of signal transducers appear to be assembled in
      different configurations, especially with respect to SHPTP-2. Both MGDF and IL-3
      induce tyrosine phosphorylation of STAT3 (APRF) and STAT5 (MGF), with MGDF
      favoring STAT3 while IL-3 predominantly causes STAT5 phosphorylation. In
      addition, some proteins become tyrosine-phosphorylated in response to MGDF only,
      suggesting that we may have detected differentiation-specific signal transducers.
      These include a number of high-molecular-weight proteins (140 to 200 kD) and one
      28-kD protein that becomes tyrosine-phosphorylated only briefly.

PMID- 8541544
TI  - Leukemia translocation gene, PLZF, is expressed with a speckled nuclear pattern
      in early hematopoietic progenitors.
AB  - The PLZF gene was discovered by studying a rearrangement of the RAR alpha locus
      in a patient with acute promyelocytic leukemia and a t(11;17) chromosomal
      translocation. To understand further the potential role(s) of the PLZF gene
      product in hematopoiesis, we have examined its expression levels in a variety of
      murine tissues and in established cell lines that are representative of various
      stages of myeloid and lymphoid development. We show that murine PLZF(mPLZF) is
      expressed at the highest levels in undifferentiated, multipotential hematopoietic
      progenitor cells and that its expression declines as cells become more mature and
      committed to various hematopoietic lineages. Data obtained with established cell
      lines are corroborated by results showing the lack of human PLZF protein
      expression in mature peripheral blood mononuclear cells and high PLZF levels in
      the nuclei of CD34+ human bone marrow progenitor cells. Interestingly, unlike
      many transcription factors, PLZF protein in these cells possesses distinct
      punctate nuclear distribution, suggesting its compartmentalization in the
      nucleus. Taken together, our data suggest a role for PLZF protein in early
      hematopoiesis and the requirement of downregulation of its expression for proper
      differentiation of most hematopoietic lineages.

PMID- 8541545
TI  - Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under
      physiologic flow conditions.
AB  - Hemolytic uremic syndrome (HUS), which is the most common cause of acute renal
      failure in infants and small children, is caused by verotoxin (VT)-producing
      Escherichia coli infection. Endothelial injury determines microvascular
      thrombosis and evidence is available from recent studies that suggests that
      leukocyte activation participates in endothelial damage. We studied here the
      effect of VT-1 on leukocyte adhesion to vascular endothelium under physiologic
      flow conditions. Human umbilical vein endothelial cells (HUVECs) were incubated
      for 24 hours with VT-1 (0.1, 1, and 10 pmol/L) and then exposed to a total
      leukocyte suspension in a parallel plate flow chamber under laminar flow
      conditions (1.5 dynes/cm2). Adherent cells were counted by digital image
      processing. Results showed that VT-1 dose-dependently increased the number of
      adhering leukocytes to HUVECs as compared with unstimulated cells. The adhesive
      response elicited by VT-1 was comparable to that of interleukin-1 beta (IL-1
      beta), one of the most potent inducers of endothelial cell adhesiveness. Exposure
      of HUVECs to VT-1 did not affect the number of rolling leukocytes, which was
      similar to that of control values. To examine the role of adhesion molecules in
      VT-1-induced leukocyte adhesion, HUVECs were incubated with mouse monoclonal
      antibodies against E-selectin, intercellular adhesion molecule-1 (ICAM-1), and
      vascular cell adhesion molecule-1 (VCAM-1) before adhesion assay. Functional
      blocking of E-selectin, ICAM-1, and VCAM-1 on endothelial cells significantly
      inhibited VT-1-induced increase in leukocyte adhesion. In some experiments,
      before VT-1 incubation, HUVECs were pretreated for 24 hours with tumor necrosis
      factor alpha (TNF alpha; 100 U/mL), which is known to increase VT receptor
      expression on HUVECs. The number of adhering leukocytes on HUVECs exposed to TNF
      alpha and VT-1 significantly increased as compared with HUVECs incubated with VT
      1 and TNF alpha alone. These results suggest that VT-1 modulates leukocyte
      endothelium interaction, thus increasing leukocyte adhesion and upregulating
      adhesive proteins on endothelial surface membrane.

PMID- 8541546
TI  - Detection and analysis of an alternatively spliced isoform of interleukin-6 mRNA
      in peripheral blood mononuclear cells.
AB  - Oligonucleotide primers for human interleukin-6 (IL-6) that bracketed the entire
      coding region of the gene were used in reverse transciptase-polymerase chain
      reaction (RT-PCR) studies to examine lL-6 expression in peripheral blood
      mononuclear cells (PBMC). In addition to the predicted 0.64-kb RT-PCR product, a
      second 0.45-kb product was observed. Cloning and dideoxy sequence analysis of
      this product revealed evidence for an alternatively spliced lL-6 transcript
      lacking exon II. Further RT-PCR analysis using forward primers ending at or one
      base before the exon I donor splice site again yielded both products. Additional
      primers were designed and successfully used to selectively distinguish the two
      forms of IL-6 transcript. Both transcripts were prominent in peripheral blood
      monocytes and lymphocytes, whereas only the 0.64-kb, full-length transcript was
      prominent in the lL-6-producing 5637 (human bladder carcinoma) cell line.
      Northern analysis revealed, in addition to the predominant 1.3-kb transcript,
      several minor transcripts at 1.9 to 4.8 kb that hybridized with the alternatively
      spliced cDNA probe but not with an exon II probe. Western analysis revealed lL-6
      polypeptides of predicted size (26 to 29 kD) in culture medium from PBMC, while
      showing an immunoreactive band at 17 kD in cell lysates. These findings suggest
      the existence of an alternatively spliced form of lL-6 mRNA, which would encode
      for a polypeptide missing the gp130 interactive (signal-transducing) domain
      contained in exon II while retaining the lL-6 receptor (p80) domain. Such a
      molecule could in theory function as a natural antagonist of lL-6, as it would be
      expected to bind to the IL-6 receptor but not lead to signal transduction.

PMID- 8541547
TI  - Distinction between gamma c detection and function in YT lymphoid cells and in
      the granulocyte-macrophage colony-stimulating factor-responsive human myeloid
      cell line, Tf-1.
AB  - Peripheral blood monocytes respond to interleukin-2 (lL-2) and express the gamma
      common (gamma c) subunit of the lL-2 receptor (lL-2R) complex. However, the role
      of lL-2 in myeloid development has recently become of interest for several
      reasons, including the effect gamma c mutations may or may not have on myeloid
      development in patients with XSCID. Many studies of lL-2 function in the myeloid
      cell lineage have been performed on a murine background. To study gamma c
      expression and function in human myeloid precursors, we introduced the human
      myelomonocytic cell line, Tf-1, with a retroviral vector containing the human lL
      2R beta subunit to create functional human intermediate lL-2R consisting of beta
      gamma c dimers. We have characterized this transfected variant of Tf-1 (Tf-1
      beta) with regard to its response to lL-2. Unlike the parental Tf-1 cell line
      that is deficient in both lL-2R alpha and lL-2R beta expression, the Tf-1 beta
      transfectant binds and responds to lL-2 through intermediate-affinity lL-2Rs.
      Scatchard analyses indicate the number of intermediate-affinity receptors on Tf-1
      beta is similar to the number found on the well-characterized YT cell line.
      However, detection of gamma c on Tf-1 beta cells is dramatically less than on YT
      cells by Western blot analysis and is undetectable by flow cytometric studies and
      surface iodinations. The gamma c component on YT cells is readily detected by all
      three methods. We conclude from these studies that the intermediate-affinity lL
      2Rs on the Tf-1 cell line behave differently than those on YT cells with respect
      to gamma c detection. Either the gamma c molecule itself is different, or the
      cellular environment in which it functions is altered. Elucidation of gamma c
      function on this cell line will allow for its use as a model in which other
      cytokines using gamma c (including lL-2, lL-4, and lL-15) can be studied on the
      same cellular background.

PMID- 8541548
TI  - Monosomy 7 and activating RAS mutations accompany malignant transformation in
      patients with congenital neutropenia.
AB  - Individuals with severe forms of congenital neutropenia suffer from recurrent
      infections. The therapeutic use of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) to increase the neutrophil count is associated with
      fewer infections and an improved quality of life. However, the long-term effects
      of this new therapy are largely unknown. In particular, it is unclear if myeloid
      leukemia, a known complication of some forms of congenital neutropenia, will
      occur with increased frequency among patients who receive long-term treatment
      with hematopoietic growth factors. We report 13 patients with congenital
      disorders of myelopoiesis who developed leukemic transformation with either
      myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) and 1 who
      acquired a clonal cytogenetic abnormality without evidence of MDS or AML while
      receiving rhG-CSF. The bone marrows of 10 patients showed monosomy 7 and 5 had
      activating RAS mutations. These abnormalities were not detected in pretreatment
      bone marrows and cessation of rhG-CSF was not associated with either clinical
      improvement or cytogenetic remission. We conclude that patients with severe forms
      of congenital neutropenia are at relatively high risk of developing MDS and AML.
      The occurrence of monosomy 7 and RAS mutations in these cases suggests that the
      myeloid progenitors of some patients are genetically predisposed to malignant
      transformation. The relationship between therapeutic rhG-CSF and leukemogenesis
      in patients with severe chronic neutropenia is unclear.

PMID- 8541549
TI  - The accumulation of p53 abnormalities is associated with progression of mucosa
      associated lymphoid tissue lymphoma.
AB  - The genetic mechanisms underlying the genesis of low-grade mucosa-associated
      lymphoid tissue (MALT) lymphomas and their transformation into high-grade
      lymphoma are poorly understood. p53 inactivation, commonly caused by mutation and
      allele loss, has been shown to play an important role in the early development
      and/or the late disease progression of many human tumors including lymphoid
      malignancies and, thus, may also be important in MALT lymphomagenesis. We
      examined 75 cases (48 low grade and 27 high grade) of MALT lymphoma for p53
      allele loss and mutation as well as protein accumulation. DNA samples prepared
      from microdissected cell populations were used for the detection of p53 gene
      abnormalities. Loss of heterozygosity (LOH) of the gene was detected by
      polymerase chain reaction-based analysis of p53 CA repeat polymorphism, whereas
      p53 mutation was studied by single-strand conformation polymorphism analysis and
      direct sequencing. p53 expression was assessed by immunostaining with CM1
      polyclonal antibody. p53 allele loss and mutation, which resulted in the
      alteration in the amino acid sequence, were found in both low-grade (LOH, 3 of 44
      [6.8%]; mutation, 9 of 48 [18.8%]) and high-grade (LOH, 6 of 21 [28.6%];
      mutation, 9 of 27 [33.3%]) MALT lymphomas, particularly in the latter group. p53
      staining was not observed in any low-grade tumors but in 6 high-grade cases that
      harbored missense mutations. There were also differences in the extent of p53
      abnormalities, between low- and high-grade tumors. Of the 11 low-grade tumors
      showing p53 abnormalities, only 1 tumor showed the concomitance of p53 mutation
      and allele loss, whereas in high-grade tumors, 6 of 9 affected cases displayed
      both p53 mutation and allele loss. Our results suggest that p53 partial
      inactivation may play an important role in the development of low-grade MALT
      lymphomas, whereas complete inactivation may be associated with high-grade
      transformation.

PMID- 8541550
TI  - Effect of interleukin-1 beta converting enzyme inhibitor on acute myelogenous
      leukemia progenitor proliferation.
AB  - Interleukin-1 beta (IL-1 beta) converting enzyme (ICE) is a cysteine protease
      that specifically cleaves precursor IL-1 beta to its biologically active form.
      Recent studies have also implicated ICE in the induction of apoptosis in
      vertebrate cells. Because IL-1 plays a major role in acute myelogenous leukemia
      (AML) blast proliferation, we sought to investigate the effect of ICE inhibition
      on AML progenitors. To do this, we used bocaspartyl (benzyl) chloromethylketone
      (BACMK) an inhibitor designed to penetrate cells and bind covalently to the
      active site of ICE. Our preliminary experiments showed that incubation of
      activated peripheral blood cells with 2.5 mumol/L of BAMCK downregulated
      production of mature IL-1 beta but had no effect on tumor necrosis factor-alpha.
      To test the effects of the inhibitor on AML cells, we first used the OCI/AML3
      cell line. We found that these cells produce IL-1 beta and bind the biotinylated
      cytokine and that IL-1 inhibitors, such as IL-1 neutralizing antibodies, IL-1
      receptor antagonist, and soluble IL-1 receptors, specifically inhibit OCI/AML3
      proliferation, indicating that IL-1 beta is an autocrine growth factor for
      OCI/AML3 cells. The ICE inhibitor suppressed OCI/AML3 growth in a dose-dependent
      manner (at 0.4 to 4 mumol/L) and downregulated mature IL-1 beta production, as
      assessed by Western immunoblotting. Similar results were obtained with marrow
      aspirates from 16 AML patients. The ICE inhibitor suppressed proliferation of AML
      precursors (by up to 78%; mean, 44%) in a dose-dependent fashion at
      concentrations ranging from 0.4 to 5 mumol/L but not proliferation of normal
      marrow progenitors; the suppressive effect was reversed by IL-1 beta.
      Furthermore, incubation of AML cells with 4 mumol/L BAMCK downregulated the
      production of mature IL-1 beta, suggesting that the growth-inhibitory effect is
      mediated through suppression of the biologically active cytokine. Our data
      indicate that inhibition of ICE suppresses AML blast proliferation and suggest
      that ICE inhibitors may have a role in future therapies for AML.

PMID- 8541551
TI  - BCR/ABL P210 and P190 cause distinct leukemia in transgenic mice.
AB  - DNA constructs encoding BCR/ABL P210 have been introduced into the mouse germ
      line using microinjection of one-cell fertilized eggs. Kinetics of BCR/ABL P210
      expression in transgenic mice were very similar to those of BCR/ABL P190
      constructs in transgenic mice. mRNA transcripts were detectable early in
      embryonic development and also in hematopoietic tissue of adult animals.
      Expression of BCR/ABL in peripheral blood preceded development of overt disease.
      P210 founder and progeny transgenic animals, when becoming ill, developed
      leukemia of B, T-lymphoid, or myeloid origin after a relatively long latency
      period. In contrast, P190-transgenic mice exclusively developed leukemia of B
      cell origin, with a relatively short period of latency. The observed
      dissimilarities are most likely due to intrinsically different properties of the
      P190 and P210 oncoproteins and may also involve sequences that control transgene
      expression. The delayed progression of BCR/ABL P210-associated disease in the
      transgenic mice is consistent with the apparent indolence of human chronic
      myeloid leukemia during the chronic phase. We conclude that, in transgenic
      models, comparable expression of BCR/ABL P210 and BCR/ABL P190 results in
      clinically distinct conditions.

PMID- 8541552
TI  - Role of zidovudine antiretroviral therapy in the pathogenesis of acquired
      immunodeficiency syndrome-related lymphoma.
AB  - The role of zidovudine and other antiretroviral agents in the pathogenesis of
      acquired immunodeficiency syndrome (AIDS)-related lymphomas has been somewhat
      controversial. In an attempt to elucidate the precise role of antiretroviral
      agents in the subsequent development of AIDS-related lymphoma, we performed a
      population-based, case-control study of human immunodeficiency virus (HIV)
      seropositive patients with intermediate- or high-grade lymphoma in Los Angeles
      County, California, in which information regarding use of antiretroviral
      medications was ascertained. Diagnostic biopsy material was reviewed to confirm
      intermediate-or high-grade lymphoma. A structured interview, conducted with all
      cases and controls, included information about use of zidovudine and other
      antiretroviral agents. A total of 112 HIV-infected homosexual/bisexual men with
      lymphoma were matched to 112 homosexual/bisexual men with asymptomatic HIV
      infection; 49 of the lymphoma cases were also matched to 49 additional controls
      with AIDS, as defined by conditions other than lymphoma. Positive histories of
      zidovudine use were reported by 44 (39%) lymphoma cases, 24 (21%) asymptomatic
      HIV controls, and 21 (42%) AIDS controls. The average duration of zidovudine use
      up to 12 months before lymphoma diagnosis was 19.0 +/- 13.0 months (mean +/- SD)
      for the lymphoma cases, 12.6 +/- 10.5 months for the asymptomatic controls, and
      11.0 +/- 7.1 months for the AIDS controls. When comparing the 49 HIV-positive
      lymphoma cases with their 49 matched AIDS controls, all of whom were diagnosed
      with AIDS during the same time period, the matched relative odds of lymphoma
      associated with prior use of zidovudine was 0.43 (95% confidence interval [CI] =
      0.17 to 1.12). In comparing all 112 lymphoma cases with 49 AIDS controls, the
      unmatched relative odds of lymphoma associated with zidovudine use was 0.93 (95%
      confidence interval = 0.47 to 1.83). One lymphoma case and no AIDS control cases
      had a history of didanosine use; no lymphoma case or AIDS control cases had taken
      zalcitabine. We conclude that zidovudine is not associated with an increased risk
      of development of lymphoma among HIV-infected homosexual or bisexual men.

PMID- 8541553
TI  - The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non
      Hodgkin's lymphomas/leukemias.
AB  - CD26 and CD40 ligand (CD40L) are surface molecules on human activated T
      lymphocytes that play a critical role in the regulation of lymphopoiesis. Both
      molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's
      lymphomas (NHL)/leukemias; however, little is known about their functional and/or
      clinical significance in these disorders. In this study, the pattern of
      expression of CD40L was compared with that of the CD26 molecule. A series of 67
      human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were
      evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall
      frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67
      [27%]). However, the majority of CD26-expressing cases clustered in the
      lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and
      CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas
      included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L
      coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic
      lymphoma. Thus, the expression of the two antigens was mutually exclusive in
      almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed
      either one of the molecules or the relative amounts of CD26 and CD40L were
      inversely proportional. In contrast, reactive T lymphocytes from patients with
      non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T
      cells were found to coexpress CD40L and CD26. Results of a multivariate analysis
      showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a
      worse outcome in terms of survival, as compared with patients with CD26- tumors
      (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed
      to activated or reactive normal T cells, the expression of CD26 and of CD40L is
      mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is
      restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell
      CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such
      as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may
      identify a subset of poor prognosis patients.

PMID- 8541554
TI  - Analysis of signaling events associated with activation of neutrophil superoxide
      anion production by eosinophil granule major basic protein.
AB  - This study was undertaken to identify the signaling events involved in activation
      of neutrophil superoxide anion (O2-) production by eosinophil granule major basic
      protein (MBP). MBP did not produce an immediate increase in the cytosolic free
      calcium concentration ([Ca2+]i), characteristic of phospholipase C activation,
      but did cause a gradual increase in [Ca2+]i in cytochalasin B-treated cells.
      Preincubation with 0.01 to 3 micrograms/mL pertussis toxin did not inhibit MBP
      stimulated O2- production, and MBP did not stimulate an increase in
      diradylglycerol levels. MBP did stimulate a low level of phospholipase D
      activity, as measured by a time-dependent increase in phosphatidic acid and, in
      the presence of 0.5% ethanol, phosphatidylethanol. Inhibition of MBP-stimulated
      O2- production by genistein and Western blot analysis using an
      antiphosphotyrosine antibody showed tyrosine kinase activation by MBP. Calmodulin
      antagonists (calmidazolium and W-7) caused up to 80% inhibition of MBP-stimulated
      O2- production. In agreement with the pharmacologic sensitivity, MBP did not
      stimulate any 51Cr release. These data indicate that tyrosine kinase and
      calmodulin-dependent steps are involved in the noncytotoxic stimulation of
      neutrophil O2- production by MBP.

PMID- 8541555
TI  - Nerve growth factor prevents apoptosis of rat peritoneal mast cells through the
      trk proto-oncogene receptor.
AB  - We investigated the inhibitory activity of nerve growth factor (NGF) on apoptosis
      of rat peritoneal mast cells (PMCs) and compared it with that of recombinant stem
      cell factor (rSCF), which is a mast cell growth factor. When PMCs were incubated
      up to 72 hours in the presence of control medium, internucleosomal fragmentation
      of DNA indicating apoptosis was detected by agarose gel electrophoresis and flow
      cytometry. The aged PMCs showed morphological changes typical for apoptosis, such
      as chromatin condensation and loss of microvilli of the cell membrane. Addition
      of NGF or rSCF prevented development of the characteristic DNA fragmentation and
      decreased the proportion of apoptotic cells with low DNA content values in a dose
      dependent manner. Polyclonal antibody to NGF completely abolished the inhibitory
      activity of NGF but not of rSCF. NGF-induced PMCs were in the G0/G1 phase of the
      cell cycle, but rSCF transited them from the G0/G1 phase to the S/G2M phase,
      suggesting that NGF, unlike rSCF, may have no proliferation activity to PMCs. By
      flow cytometric analysis with antibodies to NGF receptors p75LNGFR and p140trk,
      we defined that PMCs expressed p140trk but not p75LNGFR. Addition of herbimycin A
      or K-252a, tyrosine kinase inhibitors, to NGF resulted in blockage of the NGF
      induced p140trk phosphorylation and restriction of the inhibitory activity of NGF
      on apoptosis of PMCs. These results indicated that NGF suppressed apoptosis of
      rat PMCs through the p140trk tyrosine phosphorylation and possessed no
      proliferative activity. Thus, NGF may act as a key factor to promote survival of
      connective tissue-type mast cells.

PMID- 8541556
TI  - Impaired microbicidal capacity of mononuclear phagocytes from patients with type
      I Gaucher disease: partial correction by enzyme replacement therapy.
AB  - The higher susceptibility to serious bacterial infections in patients with
      Gaucher disease (GD) may be due in part to defective function of phagocytic
      cells. We studied five patients with GD (type I) and examined the ability of
      granulocytes and mononuclear phagocytes from these patients to phagocytose and
      kill Staphylococcus aureus and to generate superoxide anion (O2-) on stimulation
      with fully opsonized bacteria. Serum-opsonized staphylococci were ingested
      equally by phagocytic cells from patients and controls. In the presence of normal
      serum, the extent of killing of S aureus and the release of O2- by granulocytes
      over incubation periods of 60 minutes and 30 minutes, respectively, were also
      equivalent for patients and controls. However, we found that killing of viable
      bacteria and release of O2- by the patients' monocytes was significantly lower
      than that in cells from controls (P < .05 for both). The magnitude of differences
      in killing and O2- release between patients' cells and those from controls was
      even more profound with monocyte-derived macrophages. Enzyme augmentation with
      macrophage-targeted glucocerebrosidase preparation for 6 months at doses from 7.5
      to 10 U/kg/wk resulted in significant increases of functional activities and O2-
      generation of monocytes and macrophages along with hematologic and hepatosplenic
      improvements. These data suggest that mononuclear phagocytes from GD patients are
      defective in their ability to kill bacteria and to generate reactive oxygen
      intermediates. Our data also suggest that enzyme substitution may improve
      functions of monocytes and macrophages in patients with GD that should make them
      more resistant to severe bacterial infection.

PMID- 8541557
TI  - Mutations in the PIG-A gene causing paroxysmal nocturnal hemoglobinuria are
      mainly of the frameshift type.
AB  - Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia associated
      with somatic mutations in the X-linked gene PIG-A, which encodes a protein
      involved in the biosynthesis of glycosyl phosphatidylinositol anchors. To further
      elucidate the molecular basis of paroxysmal nocturnal hemoglobinuria, we have
      worked out a systematic and relatively rapid methodology to scan for mutations in
      the entire coding region of the PIG-A gene. By this methodology, we have
      identified 15 different somatic mutations in 12 patients. The mutations were
      spread throughout the entire PIG-A-coding region. Of the mutations, 10 caused
      frameshifts, 6 caused small deletions, 3 caused small insertions, and 1 caused
      deletion-insertion. Five single base pair substitutions caused three missense
      mutations, one nonsense mutation, and one defect in the donor splice site of
      intron 4. In each of 3 patients, two independent mutations were identified. The
      predominance of frameshift mutations may reflect selection for somatic mutations
      giving rise to clones with a completely nonfunctional PIG-A protein.

PMID- 8541558
TI  - Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of
      aplastic anemia.
AB  - Treatment of severe aplastic anemia with antithymocyte globulin (ATG) and
      cyclosporin leads to clinical remission in a large proportion of patients. As
      many as 10% to 57% of these patients, however, develop paroxysmal nocturnal
      hemoglobinuria (PNH). We and others have observed that this secondary PNH appears
      to be more indolent than classical PNH, which results from an acquired mutation
      in the PIG-A gene. In the present study, we compared PIG-A mRNA transcripts in
      affected cells from patients with secondary PNH and patients with classical PNH.
      All four of our aplastic patients who developed PNH had a negative Ham test at
      diagnosis. Two of the four showed a positive Ham test within 3 months after
      ATG/cyclosporin administration, one developed a positive test at 6 months, and
      another at 18 months after immunosuppressive therapy. All four patients remain
      transfusion-independent with no thrombotic episodes after a mean follow-up of 30
      months (range, 6 to 63 months). Reverse transcription-polymerase chain reaction
      (RT-PCR) of PIG-A transcripts in DAF-/CD59- neutrophils or lymphocyte lines of
      the four patients showed PIG-A abnormalities in all cases. Transition of C163 to
      T was found in one, a 14-bp deletion (positions 1141 to 1154) was found in the
      second, deletion of C39 was found in the third, and two mutations, transition of
      C55 to T and transversion of T762 to A, were found in the fourth. These
      abnormalities compared with findings of abnormal RNA splicing causing a 133-bp
      deletion, a 4-bp insertion (between positions 578 and 579), loss of A767, and
      loss of C575 in four patients with primary PNH. We conclude that secondary PNH
      that evolves out of aplastic anemia, like classical PNH, is associated with
      mutations in the PIG-A gene. The apparent indolent nature of this disease
      probably reflects early detection.

PMID- 8541559
TI  - A controlled comparison of the efficacy of hetastarch and pentastarch in
      granulocyte collections by centrifugal leukapheresis.
AB  - Compared with hetastarch (HS), the low molecular weight analog pentastarch (PS)
      has been reported to be equally effective for granulocyte collection by
      centrifugal leukapheresis, to result in fewer adverse donor reactions (ADR), and
      to have a more rapid elimination profile. We prospectively compared the
      granulocyte collection efficiency (GCE), granulocyte yield, and ADR in 72
      randomly paired granulocytapheresis procedures from 36 volunteer donors using the
      model CS-3000 Plus Blood Cell Separator (CS) and either PS or HS as the
      sedimenting agent. Paired collections from each donor allowed us to compare the
      two agents directly while controlling for intrinsic donor differences. In 33 of
      36 (92%) donors, HS procedures were significantly more efficient than PS
      procedures (P < .001). As an average, HS collections yielded 2.3 +/- 0.67 x
      10(10) granulocytes at 58% +/- 8.8% GCE, whereas PS procedures resulted in 1.4 +/
      0.76 x 10(10) granulocytes at 33% +/- 15% GCE. No starch-induced ADR were seen
      with either agent. For granulocyte harvests using the CS, (1) in most donors,
      using HS as the red blood cell sedimenting agent during centrifugal leukapheresis
      results in significantly higher (nearly twofold) GCE and larger granulocyte
      yields in comparison with using PS, (2) ADR were not observed with either agent,
      and (3) the potential benefit of more rapid PS elimination should be balanced
      against significantly lower granulocyte yields.

PMID- 8541560
TI  - Relevance of marrow fibrosis in bone marrow transplantation: a retrospective
      analysis of engraftment.
AB  - A retrospective study compared posttransplant engraftment parameters in 203
      patients with myelofibrosis (MF) with those in a population of 203 matched
      controls without MF. There were no significant differences between these groups
      in the proportions of patients who died without achieving engraftment and in the
      disease-free survival distributions. Furthermore, comparisons between the two
      groups of patients reaching the respective endpoints showed no differences in the
      time distributions for reaching 0.5 or 1.0 x 10(9)/L granulocytes, but the time
      to platelet transfusion independence was 3 days longer in patients with MF. In
      further analysis, results for 33 patients with severe MF were compared with those
      of their respective controls. The proportions of patients with severe MF who died
      without reaching these engraftment endpoints and the disease-free survival
      distributions in the two groups were similar. Among patients who reached the
      respective engraftment endpoints, there was no statistically significant
      difference in the pace of granulocyte recovery. In patients with severe MF, there
      was a 7-day delay in the time to reach platelet transfusion independence and a 2
      day delay in the time to reach red blood cell independence, but the differences
      were not statistically significant. The present results do not substantiate
      concerns raised by earlier studies. MF may delay the time to reach platelet
      independence by approximately 3 days and may increase platelet transfusion
      requirements, but no other perturbation of hematopoietic reconstitution was
      apparent.

PMID- 8541561
TI  - Hematopoietic stem cells in the blood after stem cell factor and interleukin-11
      administration: evidence for different mechanisms of mobilization.
AB  - Peripheral blood stem cells and progenitor cells, collected during recovery from
      exposure to cytotoxic agents or after cytokine administration, are being
      increasingly used in clinical bone marrow transplantation. To determine factors
      important for mobilization of both primitive stem cells and progenitor cells to
      the blood, we studied the blood and splenic and marrow compartments of intact and
      splenectomized mice after administration of recombinant human interleukin-11
      (rhlL-11), recombinant rat stem cell factor (rrSCF), and IL-11 + SCF. IL-11
      administration increased the number of spleen colony-forming units (CFU-S) in
      both the spleen and blood, but did not increase blood long-term marrow
      repopulating ability (LTRA) in intact or splenectomized mice. SCF administration
      increased the number of CFU-S in both the spleen and blood and did not increase
      the blood or splenic LTRA of intact mice, but did increase blood LTRA to normal
      marrow levels in splenectomized mice. The combination of lL-11 + SCF
      syngeristically enhanced mobilization of long-term marrow-repopulating cells from
      the marrow to the spleen of intact mice and from the marrow to the blood of
      splenectomized mice. These data, combined with those of prior studies showing
      granulocyte colony-stimulating factor mobilization of long-term marrow
      repopulating cells from the marrow to the blood of mice with intact spleens,
      suggest different cytokine-induced pathways for mobilization of primitive stem
      cells.

PMID- 8541562
TI  - Induction of tolerance in nondefective mice after in utero transplantation of
      major histocompatibility complex-mismatched fetal hematopoietic stem cells.
AB  - Significant morbidity and mortality are associated with the conditioning therapy
      needed for postnatal bone marrow transplantation (BMT) for inherited diseases.
      This could be eliminated with hematopoietic stem cell (HSC) transplantation in
      utero, when the immunoincompetence of the fetus permits engraftment without the
      need for immunosuppressive therapy. We have established an in utero (day 11 to
      day 13) model of HSC transplantation in nondefective, allogeneic major
      histocompatibility complex (MHC)-mismatched mice. Donor cells wre from pooled
      fetal livers of C57BL/6 (H-2b, GPI-1b) mice. Engraftment was tested by
      quantitative polymerase chain reaction (PCR) for the Y chromosome in female
      recipients (with 0.00001% sensitivity). Eight percent (3 of 36) of allogeneic
      mismatched (Balb-c, H-2d) recipients and 25% (3 of 12) of congenic (C57B1/6, GPI
      1a) recipients showed durable engraftment (male donor cells detected beyond 20
      weeks of age) based on analysis of peripheral blood leukocytes (P > .08). When
      spleen and liver were analyzed, 51% (17 of 33) of allogeneic recipients and 50%
      (6 of 12) of congenic recipients showed durable engraftment (P > .3). The percent
      donor cells that durably engrafted varied from as low as 0.0001% in spleen and
      liver to as high as 0.6% in peripheral blood. Postnatal boosting with a single
      dose of allogeneic MHC-mismatched donor cells in a tolerant, engrafted mouse
      resulted in a significant increase in donor cells in the peripheral blood from
      0.2% pre-boost to 5% 6 months after the boost. There was no evidence of
      engraftment in nontolerant mice after the postnatal boost with a similar dose of
      donor cells. Twenty-two allogeneic recipients were evaluated for donor skin graft
      acceptance at 6 to 12 months of age. Three mice with engraftment in blood and/or
      tissue permanently accepted donor skin grafts, one of them with donor cells
      detectable only in the liver. Six additional mice that showed prolonged skin
      graft acceptance had no evidence of durable engraftment in the blood but were
      engrafted in the liver and/or spleen. The degree of engraftment in tolerant mice
      was low (< or = 0.1% donor cells). We conclude that at an early gestational age
      in nondefective mice (1) high rates of durable engraftment are achievable,
      although the degree of engraftment is usually low (less than 1%); (2) the percent
      of donor cells in the peripheral blood may be increased by a postnatal boost of
      donor cells in tolerant animals without conditioning therapy; (3) MHC appears to
      have little influence on engraftment efficiency at an early gestational age; (4)
      a very small number of circulating donor cells in the blood or the tissues is
      sufficient for the induction and maintenance of tolerance, and (5) the presence
      of donor cells in the circulating blood is not necessary for prolonged skin graft
      acceptance or maintenance of permanent skin graft acceptance.

PMID- 8541563
TI  - Detection of clonal CD34+19+ progenitors in bone marrow of BCL2-IgH-positive
      follicular lymphoma patients.
AB  - The frequent occurrence of BCL2-IgH rearrangements in follicular lymphoma (FL)
      makes detection of low numbers of tumor cells possible by polymerase chain
      reaction (PCR). The presence of BCL2-IgH in the bone marrow (BM) and peripheral
      blood of many FL patients at the time of autografting has led to the suggestion
      that selection of the CD34-enriched fraction may lead to reinfusion of lower
      numbers of tumor cells. To address this issue, we PCR-amplified BCL2-IgH from
      fluorescence-activated cell sorting (FACS)-purified BM CD34+ and CD34- fractions
      in seven FL patients showing a PCR-detectable translocation in the major
      breakpoint region of BCL2, five of which showed morphological BM involvement. The
      total CD34+ fraction showed diminished but residual positivity in the first two
      cases tested. Therefore, BM cells from the remaining five patients were sorted
      for the CD34+19- immature population, the CD34+19+ B-cell precursors, and the
      CD34-19+ mature B-cell fraction. The CD34+19- subpopulation was negative in four
      of five, despite evident BM infiltration in three cases. In contrast, the
      CD34+19+ fraction was positive in all three cases tested. These cells represented
      0% to 50% (mean, 18%) of the total CD34+ population, suggesting that, if
      reinfusion of BCL2-IgH-positive cells plays a role in postautograft relapse in
      FL, therapeutic CD34 selection procedures should include additional purging of
      the CD34+19+ B-cell precursors or, at least, assessment of the proportion of
      CD19+ cells in the CD34+ fraction and its correlation with clinical outcome
      postreinfusion.

PMID- 8541564
TI  - Cord blood collection: effects on newborns (medical-legal)

PMID- 8541565
TI  - Risk of thrombosis in patients homozygous for factor V Leiden.

PMID- 8541566
TI  - Presence of Epstein-Barr virus viral interleukin-10 in the serum of patients with
      non-human-immunodeficiency-virus-related diffuse large-cell non-Hodgkin's
      lymphomas.

PMID- 8541567
TI  - Expression of the tumor suppressor gene WT1 in both human and mouse bone marrow.

PMID- 8541568
TI  - Soluble interleukin-2 receptor: a useful prognostic factor for patients with
      hemophagocytic lymphohistiocytosis.

PMID- 8541569
TI  - Leukocyte rolling increases with age.

PMID- 8541570
TI  - Manduca sexta lipid transfer particle: synthesis by fat body and occurrence in
      hemolymph.
AB  - Lipid transfer particle (LTP) is present in hemolymph of the tobacco hornworm
      Manduca sexta. Biosynthesis of LTP, occurrence in hemolymph, and the role of LTP
      apoproteins in the lipid transfer reaction were investigated using antibodies
      specific for LTP or for each of the apoproteins. In vitro protein synthesis
      followed by immunoprecipitation demonstrated that LTP is synthesized by the fat
      body and secreted into the medium. In contrast to apolipophorin III, an
      exchangeable apoprotein of lipophorin (the major lipid transport protein in
      hemolymph), apoLTP-III could not be detected free in hemolymph. LTP
      concentrations in the hemolymph were measured by a sandwich ELISA using a mouse
      monoclonal antibody against apoLTP-III as capturing antibody and rabbit
      polyclonal antibody against apoLTP-I as detecting antibody. LTP concentration
      increased during the late fifth instar larval stage, followed by a decrease in
      the wandering stage. Subsequently, LTP concentrations were strongly increased in
      hemolymph of adult moths. The role of the three apoproteins of LTP in the lipid
      transfer reaction was analyzed using apoprotein-specific antibodies. All three,
      apoLTP-I, -II, and -III, appeared to be important for lipid transfer activity, as
      shown by inhibition of lipid transfer by antibodies specific for each of the
      three apoproteins.

PMID- 8541571
TI  - Alteration of arachidonate levels in tick salivary glands by dietary modification
      of host blood lipids.
AB  - Tick saliva contains prostaglandins of the 2-series, believed to facilitate
      bloodmeal acquisition. Because ticks cannot synthesize the prostaglandin
      precursor, arachidonic acid, investigations were undertaken to study the uptake,
      incorporation, and distribution of arachidonic acid in the salivary glands of the
      lone star tick in vitro and in vivo. Uptake of [3H]arachidonate by isolated
      salivary glands was reduced in the presence of low concentrations of arachidonic
      or eicosapentaenoic acids, but much higher, non-physiological concentrations of
      oleic and linoleic acids were required to inhibit [3H]arachidonate uptake. The
      incorporation of [3H]arachidonate into triglycerides increased at high
      concentrations of arachidonic or eicosapentaenoic acid, but not at any
      concentration of oleic or linoleic acid. Eicosatetraynoic acid greatly inhibited
      [3H]arachidonic acid. Guinea pigs fed hydrogenated coconut oil,
      safflower/primrose oil, or fish oil exhibited altered blood lipids; notably
      increased levels of eicosapentaenoic acid when fed fish oil. Salivary gland
      lipids in ticks fed on these hosts were also altered. Ticks parasitizing fish oil
      fed guinea pigs contained high levels of eicosapentaenoic acid with a 30%
      reduction in arachidonate levels. The results demonstrated that eicosapentaenoic
      acid in the host diet had profound effects on arachidonate assimilation by tick
      salivary glands, which could lead to altered prostaglandin content in tick
      saliva.

PMID- 8541572
TI  - High prevalence of hepatitis C virus infection in a small central Italian town:
      lack of evidence of parenteral exposure.
AB  - In the spring of 1994, anti-HCV prevalence and associated risk factors were
      evaluated in 681 subjects representing all age-groups in the general population
      of a small central Italian town. The overall anti-HCV prevalence was 8.4%,
      ranging from 3.7% in the 30-39 age-group to 18.2% (p < 0.01) in the 60-70 age
      group; no subject below 30 years of age was positive. Multiple logistic
      regression analysis showed that the only variables independently associated with
      anti-HCV positivity were awareness of unspecified liver disease (O.R. 3.58), age
      > 45 years (O.R. 2.72), and lowest number of years of schooling (O.R. 11.0) while
      no association was found with any parenteral exposure such as blood transfusion,
      intravenous drug use, major or minor surgical intervention, use of glass syringes
      or dental therapy. The HBsAg prevalence in this population was 1.3%, which
      corresponds to the rate reported in central Italy. These findings show a high
      level of HCV endemicity, with no evidence of parenteral exposure.

PMID- 8541573
TI  - Portal venous blood flow unaltered in cirrhotic patients given metoclopramide
      injections.
AB  - The effects of metoclopramide on blood flow in portal and left gastric veins and
      cardiovascular haemodynamic variables were studied in 30 patients with both liver
      cirrhosis and oesophageal varices. Measurements were made under baseline
      conditions and after the intravenous administration of saline, metoclopramide 10
      mg, and metoclopramide 20 mg. Portal haemodynamics, including portal and left
      gastric veins were studied using pulsed Doppler ultrasound. In all groups, the
      blood flow and the maximal diameter of portal and left gastric veins, and heart
      rate remained unchanged. However, metoclopramide 10 mg significantly decreased
      the mean arterial pressure 15 minutes after administration while metoclopramide
      20 mg decreased it 30, 45 and 60 minutes after administration. Therefore,
      metoclopramide apparently does not alter the blood flow of the portal venous
      system in these patients.

PMID- 8541574
TI  - Gastric eicosanoid synthesis in normal subjects and alcoholics after ethanol
      stimulation.
AB  - This work studied the effect of different ethanol concentrations on the
      eicosanoid accumulation in human gastric incubates of healthy volunteers and
      chronic alcoholics, determining the in vitro eicosanoid release both in the basal
      condition and after different ethanol concentrations. The basal release of PGE2
      and LTC4 in alcoholics is higher than in healthy volunteers. Various alcohol
      concentrations cause an increase in LTC4 and PGE2 in healthy volunteers; we
      observed no LTC4 increase in alcoholics and although PGE2 levels increased after
      20% ethanol, they remained constant at higher ethanol concentrations.

PMID- 8541575
TI  - Rare presentation of endocrine pancreatic tumour: a case of glucagonoma without
      necrolytic migratory erythema?
AB  - The case of a 61-year-old woman with a probable pancreatic glucagonoma in
      reported. The clinical peculiarity of this case is the lack of the characteristic
      necrolytic migratory erythema (NME); the patient presented asthenia, weight loss
      and hyperglycemia. Ultrasonography, CT-scan and arterography showed a irregular
      pancreatic mass and secondary diffuse hepatic lesions. Fine needle aspiration
      cytology with immunohistochemistry and glucagon serum levels yielded to the
      diagnosis. Surgical treatment was not proposed because of the advanced stage of
      the disease; therefore, chemotherapy (streptozotocin, 5-fluorouracil) was
      performed. During a 16-month follow-up period the patient did not develop NME.

PMID- 8541576
TI  - Fatal bleeding after fine-needle aspiration biopsy of the liver.
AB  - Ultrasonographic-guided fine-needle aspiration (FNA) biopsy has become a routine
      diagnostic procedure in the histological evaluation of both focal and chronic
      liver diseases. It is a safe and low-cost procedure that may be quickly and
      easily performed by radiologists and gastroenterologists. Severe and unexpected
      complications, of FNA biopsy, are rarely observed, haemorrhage being the most
      frequent and often fatal (1,2). This report presents the case of a patient with
      chronic liver disease who died of massive hemorrhage due to a FNA biopsy
      complication.

PMID- 8541577
TI  - Chronic cholecystitis with features of diffuse inflammatory pseudotumour: a
      clinico-pathological case study and review of the literature.
AB  - A case of chronic cholecystitis with features of inflammatory pseudotumour is
      presented. The patient, a 69-year-old man, was admitted for epigastric pain,
      nausea, vomiting, and fever. Ultrasound examination of the abdomen revealed
      diffuse thickening of the gallbladder wall, and numerous calculi inside, without
      dilatation of the intra and extrahepatic biliary ducts. Cholecystectomy was
      performed. Histological examination confirmed the diffuse thickening of
      gallbladder wall, revealing a diffuse chronic inflammatory process with a huge
      fibroblastic and myofibroblastic proliferation associated with plasma cells,
      lymphocytes, macrophages, granulocytes, and rare giant multinucleated cells. Only
      one similar case has been quoted in the literature so far.

PMID- 8541578
TI  - Does tauroursodeoxycholic acid (TUDCA) treatment increase hepatocyte
      proliferation in patients with chronic liver disease?
AB  - Despite numerous studies on the effects of bile salts therapy in chronic liver
      disease, there are no reports on the influence such therapy has on hepatocyte
      proliferation. The aim of this preliminary study was to evaluate the effect of
      TUDCA on hepatocyte proliferation in 5 patients with HCV-correlated chronic liver
      disease. All patients were treated with TUDCA (10-13 mg/day) for three months and
      the determination of PCNA (Proliferating Cell Nuclear Antigen) expression was
      used to assess the proliferative activity of hepatocytes at the beginning and at
      the end of treatment. TUDCA reduced both ALT and Knodell's score in the 5
      patients in whom a significant increase of PCNA-LI (p < 0.05) was observed after
      treatment. TUDCA administration seems to stimulate hepatocyte proliferation in
      man.

PMID- 8541579
TI  - An update on histamine receptors and gastroprotection.

PMID- 8541580
TI  - Appearance of HBV mutants during chronic infection.

PMID- 8541581
TI  - Hepatic transport of bile acid and effect of conjugation.
AB  - Biliary transport of bile salts was investigated by measuring: 1) biliary
      transport maxima values (Tm) for different conjugated bile salts; and 2) biliary
      excretion of unconjugated bile salts relative to their conjugates under the
      continuous i.v. infusion of various unconjugated bile salts. The order of Tm
      values found in the rat of both sexes was tauro (and glyco) ursodeoxycholate
      (TUDC, GUDC), tauro alpha- and beta-muricholate (T alpha-MC, T beta-MC) >
      taurocholate(TC) > taurochenodeoxycholate (TCDC), while in female hamsters it was
      TC > TCDC > TUDC. The differences in the Tm order between rats and hamsters cast
      doubt on the currently proposed view that the apparent Tm values of bile salts
      are primarily determined by their physical-chemical properties (detergent
      property in particular). The biliary excretion of unconjugated bile salts was
      most efficient with ursocholate (UC) and alpha-MC followed by beta-MC, with UDC
      (and probably 7 ketolithocholate) being the least efficient for excretion. Thus,
      while for some bile salts such as cholate and UC, the amidation is not a
      prerequisite to their efficient excretion, for other bile salts such as UDC, the
      amidation is an excellent mechanism for facilitating the biliary excretion. In an
      attempt to explain the above order for the efficacy of the biliary excretion of
      unconjugated bile salts on the basis of their physical-chemical properties, we
      must remember that unlike rats, the biliary excretion of dehydrocholate and
      cholate in dogs is more limited than their respective taurine
      conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541582
TI  - Pyrethroid-sprayed tents for malaria control: an entomological evaluation in
      Pakistan.
AB  - Field trials were undertaken in the North West Frontier Province of Pakistan to
      determine the effects of pyrethroid-sprayed tents on feeding success, mortality
      and biting-rates of wild mosquitoes attracted to bait cows confined within the
      tents. Under natural conditions, endophagic mosquitoes rested only briefly in
      untreated tents during the night, followed by complete exodus at dawn. In tents
      sprayed on the interior surface with permethrin 0.5 mg/m2 or with deltamethrin
      0.03 g/m2 the biting rate of Anopheles stephensi was reduced by about 40%;
      deterrency against culicines and other anophelines was much less. Mortality-rates
      of bloodfed mosquitoes from the treated tents were 75% An.stephensi, 65%
      An.subpictus but only 10% of culicines. Outer fly-sheets prolonged the effective
      life of the treatment; bioassays on the sprayed inner-sheets showed that
      insecticidal efficacy remained high for over a year, whereas on tents without fly
      sheets permethrin residual efficacy declined rapidly 20-40 weeks post-treatment.
      It is concluded that tent-spraying with fast-acting photostable residual
      pyrethroid insecticide would probably provide effective protection against
      malaria transmission for the inhabitants of tents in any part of the world where
      the vector mosquitoes are endophilic and susceptible to pyrethroids.

PMID- 8541583
TI  - Antibodies to Anopheles midgut reduce vector competence for Plasmodium vivax
      malaria.
AB  - Anopheles tessellatus mosquitoes ingested Plasmodium vivax gametocytes in human
      erythrocytes suspended in rabbit sera with and without anti-mosquito midgut
      antibodies. When the mosquito bloodmeal contained anti-midgut antibodies, fewer
      oocysts of P.vivax developed on the mosquito midgut and the proportion of
      mosquitoes becoming infected was significantly reduced. Complement inactivated
      serum also reduced the infection rate and load. A second bloodmeal containing
      anti-midgut antibodies, given 48 or 72 h later, did not enhance the transmission
      blocking effect. IgG purified from anti-midgut sera was shown to mediate the
      transmission-blocking effect.

PMID- 8541584
TI  - Analysis of stage-specific and shared antigens derived from Rhipicephalus
      sanguineus by electrophoresis and western blotting.
AB  - We carried out an SDS-PAGE analysis of antigens of Rhipicephalus sanguineus using
      extracts of eggs (EE), larvae (LE), nymphs (NE), male salivary glands (MSGE),
      male midguts (MME), female salivary glands (FSGE) and female midguts (FME). Under
      non-reducing conditions a common band of about 205 kDa was observed. EE, LE and
      NE extracts showed groups of bands between 150 and 75 kDa. A protein pattern was
      observed in FSGE extract with a group of bands between 75 and 50 kDa and four
      bands between 15 and 6.5 kDa. In this case an apparently exclusive band of
      molecular weight about 25 kDa was observed. Under reducing conditions
      similarities between LE and NE extracts increased, separating from the EE
      pattern. On the other hand, we have determined the presence of stage-specific and
      common antigens on EE, LE, NE, MSGE, MME, FSGE and FME extracts of R.sanguineus
      by means of immunoblots using polyclonal sera of rabbits infested with larvae,
      nymphs or adults of this tick. EE extract was only recognized by the anti-larva
      sera. Higher reactivity was observed when the extracts were tested with anti
      adult sera. In these experiments a very prominent band of molecular weight about
      45 kDa was detected. This band was not observed under reducing conditions. Higher
      reactivity with anti-adult sera was observed against FSGE extract.

PMID- 8541585
TI  - A comparison of Glossina morsitans centralis originating from Tanzania and
      Zambia, with respect to vectorial competence for pathogenic Trypanosoma species,
      genetic variation and inter-colony fertility.
AB  - Two laboratory strains of Glossina morsitans centralis originating from different
      fly-belts (one from Singida, in Tanzania, and the other from Mumbwa, in Zambia)
      were compared with respect to vectorial competence for pathogenic Trypanosoma
      species, genetic variation and inter-colony fertility. The vectorial competence
      of G.m.centralis of Tanzanian origin for Trypanosma vivax and T. congolense is
      similar to, whereas for T.brucei brucei it is lower than the colony of Zambian
      origin. Nevertheless, these two laboratory strains of G.m.centralis showed levels
      of susceptibility to the three pathogenic Trypanosoma species which were much
      greater than previously observed in laboratory colonies of other Glossina
      species. Electrophoresis of fifteen enzymes revealed that the two colonies differ
      significantly in allele frequencies at only three loci that are relatively close
      together on one of the autosomes. Hybridization experiments revealed that
      G.m.centralis from the two fly-belts are consubspecific.

PMID- 8541586
TI  - Seasonal abundance, biting cycle and parity of the mosquito Haemagogus
      leucocelaenus in Trinidad, West Indies.
AB  - Adult female populations of Haemagogus leucocelaenus (Dyar and Shannon), the
      sylvan vector of yellow fever, were monitored weekly during 1981-82 by human
      collectors on the ground at Point Gourde in Chaguaramas Forest, 16 km west of
      Port of Spain, Trinidad. Hg.leucocelaenus showed only diurnal landing activity,
      from 06.00 to 18.00 hours (sunrise to sunset, universal time), with a single peak
      of activity between 10.00 and 14.00 hours. Densities of Hg.leucocelaenus during
      the wet season (May-November) were about double the level recorded during the dry
      season (December-April). Monthly parous rates averaged 53.9% (range 25-90%) and
      some females were up to five-pars. Retained eggs (range 2-6, mean 4/female) were
      found in the ovaries of 0.34% of landing females, all of which had stage 1
      ovarian follicles for the next gonotrophic cycle. Therefore blood-feeding is not
      inhibited by egg retention. Hg.leucocelaenus vector potential is reappraised in
      the light of these findings.

PMID- 8541587
TI  - Comparison of carbon dioxide, octenol and a host-odour as mosquito attractants in
      the Upper Rhine Valley, Germany.
AB  - Field studies were conducted in the Upper Rhine Valley to determine the responses
      of mosquitoes to CDC traps baited with either CO2, octenol, light or paired
      combinations of these. Among eight mosquito species caught, the attractant effect
      on trap catches was studied in the four most abundant: Aedes vexans, Ae.rossicus,
      Ae.cinereus and Culex pipiens. Traps baited only with light or octenol caught few
      mosquitoes, whereas many were caught by traps baited with CO2 alone or in
      combination with either of the other candidate attractants. CO2 baited traps,
      with or without light, caught the most Aedes. The combination of CO2 and octenol
      attracted most Cx pipiens, but this apparent synergy was not significant. Using a
      caged hamster compared to CO2 as bait in a CDC light-trap with only intermittent
      fan suction, the hamster attracted less mosquitoes than CO2 emitted at a rate of
      225 g/h on days 1 and 2, whereas on days 3 and 4 the smell from the hamster's
      cage became significantly more attractive than this rate of CO2 for all species
      of mosquitoes.

PMID- 8541588
TI  - Differential lipid reserves influence host-seeking behaviour in the mosquitoes
      Aedes cantans and Aedes punctor.
AB  - Lipid reserves of bait-caught female Ae.cantans and Ae.punctor mosquitoes
      (Diptera: Culicidae) were significantly higher than in teneral females. Female
      Ae.cantans given access to 10% w/v sucrose solution post-emergence showed an
      ability to synthesize lipid and, after 192 h, they were willing to take a
      bloodmeal from a human volunteer. At this point, mean lipid reserves were not
      significantly different from mean lipid reserves of bait-caught females. Prior to
      192h, females would not take a bloodmeal and lipid reserves were significantly
      lower than in bait-caught females. Female Ae.punctor given access to 10% w/v
      sucrose solution post-emergence also showed an ability to synthesize lipid.
      Females of this species were willing to feed from a human host after only 48 h,
      at which point lipid content was not significantly different from that in bait
      caught females. The level of lipid reserves in females coming to bait differs
      significantly between species: Ae.cantans has lipid reserves approximately double
      those of Ae.punctor. In addition, Ae.punctor is able to synthesize lipid to a
      level comparable with that found in bait-caught females after only 24 h, whilst
      it takes 192 h for Ae.cantans females to synthesize the amount of lipid found in
      host-seeking females, when allowed free access to sugar. Physiological
      differences in lipid synthesis and the level of lipid reserves required may
      therefore explain the differences observed between the species in the time taken
      to initiate host seeking.

PMID- 8541589
TI  - Faeces feeding by adult Phormia regina (Diptera: Calliphoridae): impact on
      reproduction.
AB  - Fresh beef liver, sugar, and five different types of faeces were evaluated as
      supportive diets for egg development in the blowfly Phormia regina. Females on a
      sugar diet were unable to develop follicles beyond stage 3, whereas liver proved
      to be the best diet for complete egg maturation. Some faecal diets were unable to
      support egg maturation when fed upon for a short period of time; however, longer
      periods of feeding produced complete egg maturation. The necessity to feed for
      longer periods of time in order to produce eggs on most of these diets was
      attributed to their low protein content. Males, in a shorter period of time than
      females, obtained enough protein from faeces to activate the neuroendocrine
      system involved in mating.

PMID- 8541590
TI  - A simple, sterile food source for rearing the larvae of Lucilia sericata
      (Diptera: Calliphoridae).
AB  - Larvae of the sheep blowfly Lucilia sericata (Meigen) were reared on various
      mixtures of pureed liver, agar, brewer's yeast and trypsin, in order to develop a
      simple, sterile, tissue-based diet. Growth and survival rates of larvae reared on
      a sterile 1:1 mixture of pureed liver with 3% Bacto agar equalled or exceeded
      those of larvae reared on raw liver. The addition of yeast and/or trypsin to the
      medium was of no additional benefit. This sterile, homogenous, tissue-based
      substrate offers a simple, convenient, inexpensive growth medium for rearing
      larvae for maggot therapy, and for testing the effects of various chemicals and
      dietary constituents on necrophagous insect larvae. It may be useful, therefore,
      in studies of myiasis, forensic entomology, and toxicology. This rearing medium
      also has the advantage that it can be stored for many months at room temperature
      without progressive decomposition or offensive odour.

PMID- 8541591
TI  - Effect of host packed cell volume on the bloodmeal size of male tsetse flies,
      Glossina pallidipes.
AB  - Haematin contents of engorged, male tsetse flies, Glossina pallidipes Austen,
      were compared with the packed cell volumes of oxen on which they had fed.
      Haematin contents increased with packed cell volume up to packed cell volumes of
      approximately 30%. Haematin contents appeared to level off or decline with
      further increase in packed cell volume. These results support a model of blood
      feeding in tsetse flies in which the rate of blood consumption decreases as
      packed cell volume increases, because of increase in blood viscosity, and tsetse
      are unable to compensate for the decrease in consumption rate by feeding for a
      longer time. After allowing for the effects of packed cell volume, bloodmeal
      sizes of tsetse increased with ox body temperature.

PMID- 8541592
TI  - Brindley's gland exocrine products of Triatoma infestans.
AB  - Volatile exocrine products of the metathoracic Brindley's glands in Triatoma
      infestans (Hemiptera: Reduviidae) were obtained by dissection and by sampling the
      air passed over agitated live adults. Isobutyric acid was the main component in
      the glands, together with isobutyl, isoamyl and amyl alcohols, 2-phenylethanol
      and other carboxylic acids and esters. Isobutyric acid, isobutyl, isoamyl and
      amyl alcohols and ester were also found to be emitted into the air, apparently
      for defence. No volatile products were detected in the metasternal glands.

PMID- 8541593
TI  - Evaluation of non-conventional treatments for control of the biting louse
      (Bovicola ovis) on sheep.
AB  - A variety of non-conventional treatments was applied to biting louse (Bovicola
      ovis) infested sheep in order to evaluate ways in which farmers could control the
      louse infestations and still maintain Organic Production Standards. In one trial,
      louse scores of sheep shorn but kept dry or wetted by water alone or with water
      plus detergent were compared with unshorn sheep treated similarly. Shearing alone
      accounted for a 35.7-66.3% reduction in mean louse scores. Wetting alone either
      with water or with water and added detergent accounted for a 26.9-35.3% reduction
      in mean louse scores. The combined effects on mean louse scores of shearing and
      wetting, as opposed to shearing alone, were statistically significant on two of
      the three farms at 32-35 days post-treatment. The effects persisted for the
      duration of the trial (between 48 and 52 days), at which point shearing and
      wetting with detergent provided 95.3-99.6% control of lice. In a second trial, a
      range of insecticidal substances considered acceptable by Organic Production
      Standards, azadirachtin (neem), pyrethrum, soap, was applied to louse-infested
      sheep and their efficacy compared with that of a commercial formulation of
      cypermethrin. The sheep treated with azadirachtin and pyrethrum had significantly
      fewer lice than either the control or soap treated sheep over the 48 days of the
      trial. Neither azadirachtin nor pyrethrum were significantly less effective than
      cypermethrin. Control (reduction in louse score) of 85.0-100% was achieved over
      the period of the trial. It is concluded that most of the non-conventional
      treatments evaluated had a useful and cost-effective role to play in reducing
      louse numbers on sheep for at least 40-50 days. The lack of persistence compared
      with that obtained with conventional insecticides was the only apparent drawback.

PMID- 8541594
TI  - Movement of Anopheles gambiae s.l. malaria vectors between villages in The
      Gambia.
AB  - Movement of mosquitoes belonging to the Anopheles gambiae complex (mixed wild
      populations of An.arabiensis, An.gambiae and An.melas) between three neighbouring
      rural villages in The Gambia was investigated by mark-release-recapture. A total
      of 12,872 mosquitoes were collected in bednets, marked with a magenta fluorescent
      powder and released over a 15-day period in one of the villages. A further 15,507
      mosquitoes were collected in exit traps, marked with a yellow powder and released
      over the same period. Mosquitoes were captured daily in all three villages using
      pyrethrum spray catches, as well as bednet and exit trap catches. The catching
      period extended for 6 days after the last day of release. Of the mosquitoes
      released, 372 (1.3%) were recaptured 2-21 days later. Of these recaptures, 272
      were caught in the release village, and 98 were caught in other villages situated
      1-1.4 km away. The 'movement index' between villages was calculated as 17.2%
      (12.2-22.4% confidence limits) for mosquitoes released after feeding and 20.1%
      (14.7-25.3%) for those released unfed. These results suggest that movement of
      mosquitoes between neighbouring villages in The Gambia seriously affects the
      entomological evaluation of pyrethroid-impregnated bednet programmes in areas
      where treated and untreated villages are interspersed.

PMID- 8541595
TI  - Incrimination of Phlebotomus papatasi as vector of Leishmania major in the
      southern Jordan Valley.
AB  - The status of sandflies as vectors of cutaneous leishmaniasis in the southern
      Jordan Valley was investigated during 1992. Sandflies were collected from
      domestic habitats and from burrows of Psammomys obesus. Of 686 Phlebotomus
      papatasi females collected from burrows, fourteen harboured promastigotes in
      their guts. On the other hand, none of 1446 P.papatasi females collected from
      domestic habitats were found infected. The highest infection rate (5.5%) was
      recorded in November at the end of the sandfly season. Six leishmanial stocks
      isolated from P.papatasi females were typed by cellulose acetate electrophoresis
      using the six enzymes G6PDH, 6PGDH, PGI, PGM, FK and ME. Five of the leishmanial
      stocks were identical to a Leishmania major reference strain (MHOM/SU/73/5-ASKH).
      The sixth isolate was a 6PGDH variant of L.major. These findings present the
      first direct evidence of the role of P.papatasi as a vector of L.major in Jordan.

PMID- 8541596
TI  - Efficacy of etofenprox against insecticide susceptible and resistant mosquito
      strains containing characterized resistance mechanisms.
AB  - Etofenprox is a non-ester pyrethroid insecticide with comparable toxicity and a
      similar mode of action to other pyrethroids. Cross-resistance studies on
      mosquitoes showed no effect of carboxylesterase, elevated esterase, altered
      acetylcholinesterase or glutathione S-transferase-based resistance mechanisms on
      etofenprox toxicity, when compared to standard susceptible strains of Anopheles
      and Culex. Cross-resistance to etofenprox occurred in a pyrethroid-resistant
      strain of Culex quinquefasciatus with both oxidase and 'kdr'-like resistance
      mechanisms. Dose-response data for susceptible mosquito strains suggest that, in
      standard W.H.O. susceptibility tests of adult mosquitoes, appropriate
      discriminating concentrations of etofenprox for detection of resistance would be
      0.1% for Culex and 0.25% for Anopheles.

PMID- 8541597
TI  - Permethrin resistance in the head louse Pediculus capitis from Israel.
AB  - Head lice, Pediculus capitis, were collected from children aged 3-12 years in
      Maale Adumin, a town near Jerusalem, after reports of control failure with the
      pyrethroid insecticide permethrin. A total of 1516 children were examined: living
      lice and eggs were found on 12.1% of the children; or another 22.8% of the
      children only nits were found. Twice as many girls as boys (8.1% v 4%) were
      infested with lice and or nits. Head lice collected from infested children were
      exposed to permethrin impregnated filter-papers. Log time probit mortality (ltp)
      regression lines were calculated for mortality data and compared to ltp lines for
      a similar collection of head lice made in 1989. The regression lines for the two
      years were significantly different, with a 4-fold decrease in susceptibility at
      the LT50 level between 1989 and 1994. The slopes of the lines also suggested that
      the 1994 population was more heterogenous in its response to permethrin than the
      1989 population. In contrast, a laboratory population of body lice (Pediculus
      humanus) tested with the same batch of permethrin-impregnated papers showed a
      slight but non-significant increase in susceptibility between 1989 and 1994. The
      results suggest that resistance to pyrethroids has developed rapidly among head
      lice since permethrin was introduced in 1991 as a pediculicide in Israel.

PMID- 8541598
TI  - Detection of Plasmodium sporozoites in mosquitoes by polymerase chain reaction
      and oligonucleotide rDNA probe, without dissection of the salivary glands.
AB  - Dried Anopheles gambiae mosquito head+thorax portions, infected with Plasmodium
      falciparum sporozoites, were processed by the polymerase chain reaction. The PCR
      product was hybridized to an oligonucleotide probe (known as 114R or AW34)
      diagnostic for Plasmodium. The detection level by autoradiography was ten
      sporozoites per mosquito. Head+thorax of mosquitoes that contained mature
      P.falciparum oocysts, without sporozoites, gave no positive signal, indicating
      that the test detects only infective mosquitoes. This test can be applied to wild
      mosquito specimens collected, prepared and processed at different time intervals.
      The technique is convenient, highly sensitive, and could be used with a non
      radioactive detection system and specific probes to differentiate Plasmodium spp.

PMID- 8541599
TI  - A comparison of the susceptibility to stocks of Trypanosoma brucei brucei of
      Glossina pallidipes originating from allopatric populations in Kenya.

PMID- 8541600
TI  - Anti-oviposition and insecticidal activity of Imperata cylindrica (Gramineae).

PMID- 8541601
TI  - Susceptibility of Culicoides imicola to cyhalothrin.

PMID- 8541602
TI  - The daily distribution and circadian rhythm of detachment of engorged
      Rhipicephalus bursa ticks from lambs and rabbits.

PMID- 8541603
TI  - Digestion of ovine immunoglobulin G in larvae of the sheep blowfly Lucilia
      cuprina.

PMID- 8541604
TI  - [Sex difference of the facial profile: segments and angles, bony and cutaneous. A
      study using the discriminant function].
AB  - We bring formula of discriminate function established from cutaneous and bone
      facial profile, on the one hand for segments, and other hand for angles. We
      propose a applying to a supplementary subject, proceeding real measurements. The
      result is the position in masculinity-femininity scale. It must take into account
      two distinct components: size and shape.

PMID- 8541605
TI  - Growth of the tibia and fibula bones in human fetuses.
AB  - The growth of the long bones has been a subject of great importance lately,
      because it provides non invasive diagnosis of prenatal malformations. This study
      examines 116 tibia and fibula bones of Brazilian fetuses (17 males and 12
      females) with gestational age ranging from the 16th to the 34th week
      postconception. Only fetuses with no visible congenital malformations and with
      normal biometric parameters were considered. The bones were measured with a 0.1
      mm precision caliper and their Total Length (TL), the Ossified Diaphysis Length
      (ODL), the Diaphysis width (DW), the Proximal Epiphyss length (PEL) and the
      Distal Epiphyss Length (DEL) were studied. The Total Length (TL) and the Ossified
      Diaphysis Length (ODL) were correlated with those of the fetal Crown-Rump length
      (C-R). Our results have shown that there was an increase in all these measures,
      with no significant statistical difference observed between the left and the
      right sides. A significant correlation coefficient was found in most parts of the
      measurements studied. This study aims to provide data to be utilized in
      monitoring bone growth as well as in the diagnosis of the lower limb deformities
      during fetal period.

PMID- 8541607
TI  - A variation of the median nerve at the level of brachial plexus.
AB  - We report a variation of the median nerve at the level of brachial plexus in a 38
      years old male cadaver. The median nerve was formed by the fusion of three
      branches; two of them coming from the lateral cord, and one from the medial cord.
      The abnormal root coming from the lateral cord had a very close oblique course
      over the axillary artery. These kinds of variations are more prone to injury in
      radical neck dissections and in other surgical operations of the axilla.
      Secondly, the very close course of the unusual branch with the axillary artery
      may lessen the blood supply of the upper extremity by compressing the vessel.

PMID- 8541606
TI  - The weight of the heart in Callithrix Erxleben, 1777.
AB  - The allometric relationship between the weight of the heart and the body
      measurements was analyzed in 31 primates of genus Callithrix (C. jacchus and C.
      penicillata). The data were analyzed after logarithmic transformation using the
      model: Ln Y = Ln a + (b) Ln X. We compared with the t-test the slopes of the
      males and females and the slopes of the C. Jacchus and C. penicillata. Positive
      allometry was found to the weight of the heart in relation to the body weight
      (except to females of C. penicillata = isometry) and to sitting height in females
      of C. jacchus and males of C. penicillata. The relationship of the weight of the
      heart with the sitting height was isometric in males of C. jacchus and negative
      in females of C. penicillata. We cannot reject the null hypothesis analyzing the
      differences between the slopes of males and females. Therefore, in these two
      species of Callithrix we accept the concept of monomorphism.

PMID- 8541608
TI  - Cardiomyocyte proliferation and hypertrophy in the human fetus: quantitative
      study of the myocyte nuclei.
AB  - Quantitative analyses about the cardiac growth are important today because non
      invasive methods of diagnosis allow in vivo study of the fetal heart. Eight human
      fetuses of single pregnancy were studied. The ages of the fetuses were determined
      according to the foot length. Four fetuses were aged in the 2nd trimester and
      four fetuses were aged in the 3rd trimester of gestation. We used the dissector
      method to obtain the volume and numerical densities of the cardiac myocytes. We
      studied fifteen random dissector pairs for each specimen. For reasons of
      efficiency, one nucleus was considered one myocyte. We counted the number of the
      myocyte nuclei in the test-area appearing in an unbiased counting frame of 1600
      microns 2 on the one-slice plane. We determined the numerical density of myocyte
      nuclei (Nv[nu] 1/mm3), the volume density of the myocyte nuclei (Vv[nu]%) and the
      average volume of the myocyte nuclei (V[nu]micron 3). Both Vv[nu] and Nv[nu]
      decreased from the second to the third trimesters of gestation and these
      differences are significant (p = 0.03 a reduction of more than 40%). However, the
      V[nu] remains practically unchangeable during the last two trimesters of
      gestation (p > 0.05). During this period the cardiac weight increases almost 800%
      and, of course, we can expect that the absolute number of the myocyte nuclei
      increase so much. So, the increasing number of myocytes with the simultaneous
      decreasing of the Nv[nu] might explained by the overall growth of the myocardium.
      This fact explains why the unitary volume of the myocyte nuclei remains
      practically unchangeable during this period.

PMID- 8541609
TI  - [Measurement of the sigmoid colon and its relationship with volvulus].
AB  - Sigmoid volulus occurs more frequently in Turkish people than the European. The
      anatomy of the sigmoid colon plays an important role in the etiology. In our
      study various measurements of the sigmoid colon of 25 preserved cadavers were
      taken and the results were interpreted according to the frequency of sigmoid
      volvulus in this country.

PMID- 8541611
TI  - The poetical epidemiologist.

PMID- 8541610
TI  - [Preliminary and multidisciplinary study of three Coptic mummies of the Testut
      Latarjet museum at Lyon].
AB  - In 1901 Albert Gayet raked up from Antinoe three mummies exhibited to day at the
      Anatomy Museum of Lyon. The study of the three mummies was made in detail as to
      their dress, anthropometric and scannographic findings. The clothes were
      characteristic of coptic civilization. The radiographic date gave a life span of
      around 40 years. The X-ray imagery shows the remains of cerebral and visceral
      organs. The sexual criteria are thought to be those of two women and undetermined
      for the child. Later, several investigations like endoscopic autopsy, tooth
      microscopy and chromosomic map will be necessary.

PMID- 8541612
TI  - Truth in advertising.

PMID- 8541613
TI  - Capital punishment and the physician.

PMID- 8541614
TI  - The health status of the Providence-area homeless population.

PMID- 8541615
TI  - Can patients accurately predict how illness will change their lives?

PMID- 8541616
TI  - Health and social service utilization by older Jewish immigrants to RI from the
      former Soviet Union.

PMID- 8541617
TI  - Domestic violence: a guide for health care providers.

PMID- 8541618
TI  - HIV risk: no impact on medical student specialty choice.

PMID- 8541619
TI  - Clinic.

PMID- 8541620
TI  - AIDS clinic at the ACI.

PMID- 8541621
TI  - Student as patient: perspectives from the other side.

PMID- 8541622
TI  - Student innovations in the training of physicians at Brown: the whole patient and
      the whole physician programs.

PMID- 8541623
TI  - At the VA: through the eyes of a medical student.

PMID- 8541624
TI  - Medical students: making a difference while learning.

PMID- 8541625
TI  - Infant mortality in Rhode Island.

PMID- 8541626
TI  - Screening for non-insulin-dependent diabetes: the issues.

PMID- 8541627
TI  - Indications and donor source of hematopoietic stem cell transplants in Europe
      1993: report from the European Group for Blood and Marrow Transplantation (EBMT).
AB  - This report details the evolution of bone marrow transplantation in Europe over a
      20-year period. In 1973, 8 teams undertook a total of 16 allogeneic bone marrow
      transplants; in 1983, 97 teams performed 1353 transplants. In 1993, the numbers
      had risen to 260 teams and 7737 transplants. Donor source in 3092 cases was an
      allogeneic donor (2464 HLA-identical sibling transplants, 147 non-identical
      family donor transplants, 25 twin donor transplants and 456 unrelated donor
      transplants). For 4645 patients the transplant was autologous (2450 autologous
      bone marrow transplants, 1830 autologous peripheral blood stem cell transplants
      and 365 combined autologous peripheral blood and bone marrow transplants).
      Indications for transplants in 1993 were leukemias in 3419 patients (44%; 2332
      allogeneic, 1087 autologous), lymphoproliferative disorders in 2666 patients
      (34%; 197 allogeneic, 2469 autologous), solid tumors in 1077 patients (14%; 9
      allogeneic, 1068 autologous), aplastic anemia in 251 patients (3%; 250
      allogeneic, 1 autologous), inborn errors in 244 patients (3%; 242 allogeneic, 2
      autologous) and miscellaneous disorders in 80 patients (1%; 62 allogeneic, 18
      autologous). These data illustrate the increase of hematopoietic stem cell
      transplants as a therapeutic modality over the last 20 years in Europe.

PMID- 8541628
TI  - Nutrition support following liver transplantation: comparison of jejunal versus
      parenteral routes.
AB  - Liver failure patients are chronically malnourished at the time of transplant. We
      have used jejunostomy tubes (j-tube) placed at the time of liver transplantation
      for immediate postoperative enteral nutrition. We compared the effectiveness of
      this means of nutrition to total parenteral nutrition (TPN). Sixty-three adult
      patients fed enterally (ENT) with a semi-elemental diet were retrospectively
      compared to 21 adult controls alimented with TPN, both beginning after liver
      transplantation. Data collected included: day to initiation of nutrition, day of
      achieving goal nutrition, day of removal of nasogastric tube, day of initiation
      of oral nutrition, day of achieving oral nutritional goal, and serum albumin,
      cholesterol, SGOT, SGPT, GGT, and bilirubin. Intestinal complications of
      diarrhea, ileus, and perforation were analyzed. Statistical analyses used an
      unpaired t-test for continuous data, and Chi square for categorical data. Caloric
      requirements, percentage ideal body weight, age, and initial cholesterol and
      albumin were equal. Fifty-four of the ENT patients were fed only by j-tube; 9 ENT
      patients also required TPN. ENT patients started on nutrition sooner (3 +/- 1.7
      vs. 1.7 +/- 0.9 days, p = 0.001), reached goal oral nutrition sooner (19.5 +/- 11
      days vs. 38.6 +/- 24.6 days, p = 0.0061, Mann-Whitney U test), and had a lower
      frequency of prolonged postoperative ileus (8.3%, vs. 33%, p = 0.009) than TPN
      patients. ENT patients had a greater frequency of diarrhea than TPN controls (73%
      vs. 25%, p < 0.001). This diarrhea was self-limited, lasting 3 to 5 days, and
      responded to anti-motility drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541629
TI  - Re-evaluation of skin-explant model in graft-versus-host disease prediction.
AB  - An in vitro skin explant model has been proposed for prediction of graft versus
      host disease and reported to be highly sensitive and specific for this purpose.
      In this study we have re-evaluated this model in both HLA full-matched BMT
      recipient-donor sibling pairs and also in HLA one haplotype-matched parent
      children pairs. All assessments were made blindly by 3 independent observers. The
      predictive value of the test for the occurrence of clinical GvHD in 14 BMT
      patients was found to be less sensitive than reported previously (correlation
      coefficients were +0.019, +0.067 and -0.061 between clinical GvHD and in vitro
      primed allogeneic, primed mixed and unprimed allogeneic settings, indicating
      "poor" correlation). False positive and false negative results were high and
      there were also significant discrepancies between three blind observations in the
      grading of skin changes. Weighted kappa analysis revealed that there were "fair"
      correlations between the 3 observers (K = 0.25). These results indicated that the
      skin explant model is an unpredictable test system and there are great problems
      in standardization of the method.

PMID- 8541630
TI  - Erythrocytosis after renal transplantation: risk factors and relationship with
      GFR.
AB  - Post-transplant erythrocytosis (PTE) has been increasingly recognized as a
      complication of kidney transplantation, and several risk factors have been
      defined. Recent evidence suggests renal function may also play a role in
      hematological recovery after transplantation and risk of PTE. In this study of
      kidney transplant recipients (n = 123), simultaneous Tc99m DTPA GFR (n = 710) and
      hemoglobin levels were compared with possible clinical determinants. The
      frequency histogram of post-transplant hemoglobin was bell-shaped and
      continuously distributed above and below the arbitrary definition of PTE,
      suggesting that PTE is not a separate disease entity. Hemoglobin reached a
      plateau at 12 months after transplantation and was correlated with isotopic GFR
      (r = 0.46, p < 0.001). This consistent and statistically independent relationship
      became prominent 3 months after transplantation. Hemoglobin was independently
      predicted by multivariate analysis by time after transplantation, presence of
      polycystic renal disease, greater serum albumin and reduced serum urea (which in
      turn were reflected by number of infective and rejection episodes), shorter
      kidney anastomosis time and a higher GFR, but not by immunosuppressive therapy.
      Rejection or infection episodes impaired hematological recovery. The independent
      determinants of GFR included hematological recovery. The independent determinants
      of GFR included hemoglobin level, kidneys from young, male donors, fewer HLA-DR
      mismatches and rejection episodes, shorter time on dialysis and greater
      azathioprine dose. Renal function was not altered by therapeutic phlebotomy.
      Determination of hemoglobin level by both donor and recipient variables supports
      the relevance of tubular and glomerular function in control of erythrocystosis
      after renal transplantation. A role for renin-angiotensin mediation in the
      alteration of intraglomerular hemodynamics and erythropoietin secretion is
      postulated.

PMID- 8541631
TI  - Echo-Doppler diagnosis of renal allograft artery stenosis.
AB  - For the diagnosis of allograft artery stenosis in recipients of a renal
      transplant with hypertension a noninvasive investigation such as echo-Doppler is
      preferable to invasive methods such as angiography. Therefore we analyzed our
      experience with echo-Doppler diagnosis of renal allograft artery stenosis. In 131
      renal transplant recipients with hypertension echo-Doppler examinations were
      performed. During the examinations several features indicative of stenosis were
      measured, and intrarenal Doppler spectra were quantitatively analyzed with a user
      written program. Four patients showed signs of iliac artery stenosis. In 12
      patients a renal allograft artery stenosis was suspected on echo-Doppler
      examination. In 8 of these 12 patients angiography was performed. All these
      showed a stenosis, 6 of which had more than > 75% stenosis. In 8 patients with
      normal echo-Doppler findings angiography was performed because of highly
      suggestive clinical signs of stenosis. In 7 of these no stenosis was found and in
      one a 50% stenosis was found. Comparison of quantitative Doppler spectrum
      features from patients with (n = 6) and without severe (> 75%) stenosis on
      angiography (n = 10) showed significant differences in several Doppler
      parameters. Subsequently an analysis of the best differentiation between these to
      groups on the basis of quantitative Doppler criteria was performed. In
      conclusion, echo-Doppler examinations with quantitative analysis of Doppler
      spectra enables reliable identification of renal allograft artery stenosis.

PMID- 8541632
TI  - Pancreatic allograft thrombosis: diagnostic and therapeutic importance of splenic
      venous flow velocity.
AB  - Thrombosis of pancreatic transplant is usually diagnosed so late that graft
      pancreatectomy is the only possible operative recourse. We report 3 patients with
      portal vein thrombosis which was diagnosed by the triad decreased splenic vein
      velocity, decreased urinary amylase and slowly rising glycemia. Thrombosis was
      confirmed at the time of surgery. Thrombectomy was performed in 2 patients. One
      patient achieved long-term insulin independence while the other graft was lost to
      recurrent thrombosis and failure of thrombectomies. The third graft was removed
      primarily. This experience led us to assess the role of Duplex Color Doppler in
      five normal volunteers and 11 insulin-independent pancreatic transplant
      recipients.

PMID- 8541633
TI  - Urologic complications after simultaneous pancreas-kidney transplantation: hand
      sewn versus stapled duodenocystostomy.
AB  - Pancreas transplantation with bladder drainage of exocrine secretions may be
      associated with significant urologic complications. Stapled and hand-sewn
      duodenocystostomies were compared in 61 recipients of simultaneous pancreas
      kidney transplants. Both methods resulted in similar urologic complication and
      allograft survival rates. Duodenal segment leaks were associated with significant
      morbidity and decreased patient and allograft survival.

PMID- 8541634
TI  - Comparison of APACHE II scoring in liver and kidney transplant recipients versus
      trauma and general surgical patients in a single intensive-care unit.
AB  - Over a 26-month period we assessed the ability of APACHE II, scored on admission
      to the surgical intensive care unit (SICU), to predict the in-hospital mortality
      of liver and kidney transplant recipients either post-operatively or after
      subsequent complications, and compared these results to non-transplant SICU
      admissions. There were 866 SICU admissions, of which 128 were liver transplant
      recipients, 112 were renal transplant recipients, 211 were trauma admissions and
      415 were non-transplant/non-trauma admissions. In hospital mortalities among all
      liver transplant admissions were 0%, 10%, 38%, and 82% for APACHE II ranges of 0
      10, 11-20, 21-30 and > 30, respectively, with differences between the second and
      third, and third and fourth ranges significant (p < or = 0.05 by chi-square
      analysis). These differences were also seen when examining scores following the
      primary transplantation alone. Mortalities in corresponding APACHE II ranges for
      trauma and nontransplant/nontrauma admissions were similar. APACHE II scoring was
      not useful for renal transplant recipient, as it consistently overpredicted
      mortality. We conclude that APACHE II scoring may be useful in predicting outcome
      in post-operative liver transplant recipients, but is not useful in stratifying
      risk in renal transplant recipients due to the inherently low mortality involved.

PMID- 8541636
TI  - Successful organ donation in victims of child abuse.
AB  - Organ transplantation has become a valuable and accepted treatment for many
      patients with organ failure. A major limitation to transplantation is the
      shortage of organ donors. Due to lack of willingness by medical examiners to
      release child abuse cases for organ donation, child abuse victims are a greatly
      underutilized pool of potential donors. This paper presents a model to facilitate
      organ recovery in the child abuse victim. This protocol has been in consistent
      use in San Diego County since midyear 1991. In all cases of child abuse where the
      victim was brain dead and the family consented to organ donation, the medical
      examiner's office released the body for organ donation. Since institution of the
      model described in this paper, organ donation among child abuse victims has risen
      dramatically in San Diego County. If similar protocols are established at other
      pediatric centers, the disparity between supply and demand in pediatric organ
      donation will diminish.

PMID- 8541635
TI  - Rejection episodes after liver transplantation during primary immunosuppression
      with FK506 or a cyclosporine-based regimen: a controlled, prospective, randomized
      trial.
AB  - As part of a European multicenter study to investigate the potency of FK506 in
      primary immunosuppression after liver transplantation, this comparison with our
      conventional cyclosporine-based quadruple regimen was carried out as a
      controlled, prospective, randomized trial. The 121 patients entering the study
      were randomly assigned to receive immunosuppressive regimens consisting either of
      FK506 and prednisolone (FK/n = 61) or of cyclosporine, prednisolone,
      azathioprine, and a 7-day course of rabbit antithymocyte globulin (CsA/n = 60).
      Rejection was suspected in the case of scant production of light bile or
      biochemical graft dysfunction, without evidence of vascular, biliary, or
      infectious complications. A liver biopsy for confirmation of the diagnosis was
      obtained each time. Initial therapy entailed a 3-d course of high-dose methyl
      prednisolone. Steroid resistant rejections were treated with OKT3 monoclonal
      antibody or, in the group of primary CsA administration, conversion to FK506 as
      another treatment option. One-year patient (FK: 90.2%; CsA: 96.7%) and graft
      survival (FK: 88.5%; CsA: 91.7%) did not differ significantly. Overall, 41
      patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25
      RE in 21 patients (34.4%); CsA: 25 RE in 20 patients (33.3%)]. The histological
      grading ranged from mild (FK: 14/25; CsA: 8/25) to moderate (FK: 9/25; CsA:
      16/25) and severe (FK: 2/25; CsA: 1/25): not significantly different between the
      two groups. In the CsA-based group, three additional rejection episodes were
      classified as early chronic (n = 1) and chronic rejection (n = 2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8541637
TI  - Determinants of long-term allograft function following steroid withdrawal in
      renal transplant recipients.
AB  - We retrospectively measured changes in serum creatinine concentration as
      estimates of changes in renal function in 96 renal transplant recipients who were
      withdrawn from steroid therapy, maintained on cyclosporine and azathioprine, and
      followed for 1 to 5 years. Multivariate analyses were used to assess the
      influence of cyclosporine dose and blood levels, azathioprine dose, age, sex,
      race, diabetes, HLA match and mismatch, PRA, and history of rejection following
      steroid withdrawal on long-term allograft function. Results indicate that acute
      rejection and cyclosporine dose are the major factors influencing long-term renal
      function after steroid withdrawal. In this setting, there is an inverse
      relationship between cyclosporine dose and serum creatinine concentration for up
      to 5 years. Optimal renal function is achieved in patients receiving more than
      5.5 mg/kg of cyclosporine per day at the time of steroid withdrawal.

PMID- 8541638
TI  - Correlation between venous and capillary blood samples for cyclosporine
      monitoring in pediatric liver transplant patients.
AB  - Venipuncture has traditionally been required to monitor serum cyclosporine
      levels. This is a difficult if not impossible task in pediatric patients.
      Capillary blood sampling has eliminated the need for venous access in the
      majority pediatric laboratory investigations. Although the practice of capillary
      sampling for cyclosporine monitoring is discouraged, there has never been any
      investigation into the reliability of this method. Thus, we compared 18 capillary
      cyclosporine levels from 4 pediatric liver transplant patients to simultaneous
      venipuncture serum levels. The correlation coefficient of the paired samples
      (range 32-1005 ng/ml) was 0.914. This excellent correlation between the two
      sampling methods suggests that capillary cyclosporine levels may be adequate to
      monitor the immunosuppression of pediatric liver transplant patients.

PMID- 8541639
TI  - Protein glycation inhibitors from thyme (Thymus vulgaris).
AB  - Nonenzymatic glycation of bovine serum albumin (BSA) was inhibited in vitro by
      some extracts of 34 kinds of spices. The methanol extract of thyme (Thymus
      vulgaris) had the most potent inhibitory activity among them. Chromatographic
      purification yielded four flavonoids, quercetin (1), eriodictyol (2), 5,6,4'
      trihydroxy-7,8,3'-trimethoxyflavone (3), and cirsilineol (4). These known
      flavonoids suppressed the levels of advanced glycation end products (AGEs) and
      fructosamines, shown by the measurement of specific fluorescent groups and the
      reduction of nitroblue tetrazolium (NBT), respectively. The inhibitory activities
      were compared with those of other structure-related flavonoids and
      aminoguanidine.

PMID- 8541640
TI  - Formation of lyso-glycosphingolipids by Streptomyces sp.
AB  - The actinomycete strain Streptomyces sp. H37 produces a novel glycosphingolipid
      degrading enzyme. This strain was capable of converting ganglioside GM1 to lyso
      GM1. After cultivation for 5 days in medium containing GM1, peptone, and
      detergent, GM1 was found to be almost completely converted to lyso-GM1. The
      product was purified on a DEAE-Sephadex A-25 column and thin layer
      chromatographies. The purified lyso-GM1 was hydrolyzed by endoglycoceramidase,
      and the released oligosaccharide moiety was identified as that of GM1 by HPLC
      using the pyridylaminoderivative method. The counterpart sphingosine moiety was
      confirmed with TLC. Moreover, the structure of lyso-GM1 was ascertained by 1H-NMR
      analysis. The maximum formation of lyso-GM1 was found in 50 mM potassium
      phosphate buffer (pH 7.5) containing 0.1% glycodeoxycholate. Various lyso
      glycoshingolipids, including those of ganglio-, neolacto-, and globo-types, were
      formed from their parent glycosphingolipids using this strain.

PMID- 8541641
TI  - Efficient production of casoxin D, a bradykinin agonist peptide derived from
      human casein, by Bacillus brevis.
AB  - We efficiently produced a small peptide by the host-vector system using Bacillus
      brevis as a host. DNA encoding the physiologically functional casoxin D, composed
      of seven amino acids, was ligated in tandem. An expression-secretion vector
      containing DNA, which codes for a fusion protein of epidermal growth factor
      casoxin D pentamer, was constructed. B. brevis transformed with this plasmid
      produced about 0.5 g/liter of the fusion protein in the culture supernatant. The
      fusion protein was purified with ammonium sulfate fractionation from the
      supernatant and digested with two kinds of proteinases. A peptide well separated
      by high pressure liquid chromatography was identified as biologically active
      casoxin D.

PMID- 8541642
TI  - Effects of vitamin B6 deficiency on the conversion ratio of tryptophan to niacin.
AB  - To investigate how vitamin B6 (B6) deficiency affects the whole metabolism of
      tryptophan-niacin, rats were fed for 19 days with each of the following four
      kinds of diets; a complete 20% casein diet (control diet), the control diet
      without B6, the control diet without nicotinic acid, and the control diet without
      nicotinic acid and B6, and the urinary excretion of such tryptophan metabolites
      as kynurenic acid, xanthurenic acid, nicotinamide, N1-methylnicotinamide, N1
      methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide each and
      the enzyme activities involved in tryptophan-niacin pathway were measured. The
      urinary excretion of kynurenic acid decreased while that of xanthurenic acid
      increased drastically in the two B6-deficient groups, when compared with the B6
      containing groups. These results indicate that the rats fed with the B6-free
      diets were in the vitamin-deficient state. The conversion ratio was calculated
      from the ratio of the urinary excretion of sum of nicotinamide, N1
      methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone
      3-carboxamide, to the Trp intake. The ratio was statistically lower in the B6
      free diet than in the B6-containing diet under the niacin-free conditions.

PMID- 8541644
TI  - Molecular cloning and sequence analysis of the gene encoding the collagenase from
      Cytophaga sp. L43-1 strain.
AB  - Cytophaga sp. strain L43-1 secretes a collagenase [Y. Sasagawa et al., Biosci.
      Biotech. Biochem., 57, 1894-1898 (1993)]. A cog gene encoding the collagenase
      from this strain was cloned, and the nucleotides were sequenced. The structural
      gene of cog consisted of 3846 base pairs, which encoded a polypeptide consisting
      of 1282 amino acid residues with a predicted molecular mass of 130 kDa which was
      synthesized as a pre-matured enzyme. The deduced N-terminal 14 amino acids
      sequence, molecular mass of 120 kDa, and pI of 4.96 of the predicted matured
      enzyme were consistent with those previously found for the collagenase purified
      from the strain. The cog gene was expressed in Escherichia coli using the lac
      promoter and ribosomal binding sequence in plasmid vector pUC119 or pKK223-3, but
      not its own putative promoter and Shine-Dalgarno sequence. The consensus amino
      acid sequence (His-Glu-Xaa-Xaa-His) of an active site of the metal proteases
      including the collagenase from Vibrio arginolyticus and a series of human MMPs
      was found in the Cog protein of the strain.

PMID- 8541643
TI  - Costunolide and dehydrocostus lactone as inhibitors of killing function of
      cytotoxic T lymphocytes.
AB  - Costunolide and dehydrocostus lactone were isolated from an extract of mokko
      (Saussurea lappa Clarke) as inhibitors of killing activity of cytotoxic T
      lymphocytes (CTL). Mokko lactone was also isolated as an inactive compound from
      the extract. The structure-activity relationship indicated that alpha-methylene
      gamma-butyrolactone is required for the inhibitory effect. Costunolide markedly
      inhibited the granule exocytosis and the production of inositol phosphates in
      response to anti-CD3 monoclonal antibody (mAb) stimulation at a concentration
      that did not affect the binding of anti-CD3 mAb. Tyrosine phosphorylation induced
      by crosslinking of CD3 molecules was significantly inhibited by costunolide in a
      dose-dependent manner. These results suggest that costunolide inhibits the
      killing activity of CTL through preventing the increase in tyrosine
      phosphorylation in response to the crosslinking of T-cell receptors.

PMID- 8541645
TI  - Purification and characterization of intracellular proteinases in Pleurotus
      ostreatus fruiting bodies.
AB  - A serine proteinase (ProA, EC 3.4.22.9) and two metalloendopeptidases (ProB, EC
      3.4.99.32 and ProC, 3.4.24.4), have been purified to homogeneity from the
      fruiting bodies of Pleurotus ostreatus. ProA is a serine proteinase with a mass
      of 30 kDa, which has amidolytic and esterolytic activities besides proteolysis
      and catalyzes preferential cleavage of the peptide bonds involving the carboxyl
      groups of hydrophobic amino acid residues in oxidized bovine insulin B chain. The
      N-terminal amino acid sequence was VTQTNAPWGLSRL. ProB is a zinc-enzyme with a
      mass of 18 kDa, which is devoid of lysine, and its N-terminal sequence was
      ATFVGCSATRQ. The enzyme is inactivated completely by EDTA and 1,10
      phenanthroline, and Zn(2+)-depleted ProB can regain the activity with Zn2+, Co2+,
      or Mn2+. Specific cleavage of Pro29-Lys30 in oxidized bovine insulin B chain,
      preferential generation of lysylpeptides from proteins, and a high susceptibility
      of polylysine suggest that ProB splits specifically the peptide bonds involving
      the alpha-amino group of lysyl residues. ProC is a metalloendopeptidase of a mass
      of 42.5 kDa, and Zn2+ was the most effective divalent metal ion to activate the
      EDTA-inactivated enzyme.

PMID- 8541646
TI  - Purification and some properties of S-Hemolysin produced by Streptomyces sp.
      strain no. A-6288.
AB  - A new cytolytic toxin, designated as S-Hemolysin, was found in the culture
      filtrate of Streptomyces sp. strain No. A-6288, isolated from a soil sample. The
      molecular weight of S-Hemolysin was estimated to be 10,000 by SDS-polyacrylamide
      gel electrophoresis and to be 20,000 by Sephadex G-100. S-Hemolysin is a
      glycoprotein that is composed of 102 amino acid residues with 11.6% glucose, and
      the isoelectric point is around pH 5.8. The phospholipase C activity of S
      Hemolysin was specific for the following substrates in this order: sphingomyelin
      > lysophosphatidylethanolamine > lysophosphatidylcholine >
      phosphatidylethanolamine > phosphatidylcholine. S-Hemolysin had hemolytic
      activity against rabbit, human, and sheep erythrocytes, but did not cause
      aggregation of human platelets. These activities were accelerated with Mg2+,
      Mn2+, and Co2+ ions and inhibited by the addition of Ca2+, Cu2+, and Zn2+ ions.
      This enzyme was shown to be different from the known bacterial phospholipase C.

PMID- 8541647
TI  - Prolidase from Xanthomonas maltophilia: purification and characterization of the
      enzyme.
AB  - Prolidase (iminodipeptidase, EC 3.4.13.9) was purified from an extract of
      Xanthomonas maltophilia, by ammonium sulfate fractionation and sequential
      chromatographies on DEAE-Toyopearl, Toyopearl HW65C, FPLC-Hiload Superdex 200 pg,
      and FPLC-Hitrap Q columns, which an activity recovery of 2.3%. The enzyme was the
      most active at pH 7.5 with Leu-Pro as substrate. It was stable between pH 6.0 and
      8.5 for 60 min at 37 degrees C and retained half of activity after 60 min at 37
      degrees C. The isoelectric point of the enzyme was 3.7. Its molecular weight was
      estimated to be 100,000 by gel filtration on FPLC-Hiload Superdex 200 and 51,000
      by SDS-PAGE, suggesting that it is a dimer. It hydrolyzed dipeptides only if
      proline is located at the carboxyl terminal position. The enzyme was inhibited by
      PCMB and o-phenanthroline, and was activated by Mn2+.

PMID- 8541648
TI  - A new nucleophilic ring opening of an activated cyclopropane and a formal
      synthesis of (+/-)-carbovir.
AB  - The reaction of bicyclo[3.1.0]hexane 1, possessing a doubly activated
      cyclopropane ring, with acetic acid and potassium acetate in DMSO proceeded
      smoothly to give the adduct 2 in good yield. A formal total synthesis of the
      potent anti-HIV agent (+/-)-carbovir (9) was done by converting 2 into a known
      precursor 8 in 8 steps via allyl alcohol 7 including the regioselective
      introduction of a double bond (4 to 5) and attachment of the nucleobase using the
      Mitsunobu reaction (7 to 8).

PMID- 8541649
TI  - Base non-specific acid ribonuclease from Irpex lacteus, primary structure and
      phylogenetic relationships in RNase T2 family enzyme.
AB  - Two base non-specific acid RNases (RNase Irp1 and RNase Irp2) were purified from
      a commercial enzyme, "Driselase" (Irpex lacteus) in a homogenous state on SDS
      PAGE by several steps of chromatographic separations. RNAse Irp2 was a simple
      polypeptide with 235 amino acid residues and RNase Irp1 was a glycopeptide with
      248 amino acid residues. The amino acid sequences of both RNases were identified
      by Edman degradation of the peptides derived from these RNAses. RNase Irp1 was
      composed of the RNase Irp2 and extra C-terminal 13 residues of peptide. The
      phylogenetic relation of these RNases with the other fungal RNases already known
      was discussed. The sequence of RNase Irp2 was very highly homologous (67.5%) with
      that of RNase Le2 from Lentinus edodes.

PMID- 8541650
TI  - Low molecular weight chitosan stimulation of mitogenic response to platelet
      derived growth factor in vascular smooth muscle cells.
AB  - Low molecular weight chitosan (LMWC) (a mixture of chitooligosaccharides with
      high degrees of polymerization; an average degree of polymerization is 6.8)
      stimulated mitogenic response to platelet-derived growth factor (PDGF) in a dose
      dependent manner in cultured rat vascular smooth muscle cells, and a maximum
      effect was observed at 100 micrograms/ml. However, the mitogenic response was not
      induced when cells were incubated with LMWC alone. This stimulatory effect of
      LMWC on the mitogenic response to PDGF (a competence factor) appeared to resemble
      the effect of insulin as a progression factor. Chitooligosaccharides with higher
      degrees of polymerization were more effective, but D-glucosamine, chitobiose, and
      chitotriose were barely active. LMWC as well as PDGF induced protein tyrosine
      phosphorylation in vascular smooth muscle cells.

PMID- 8541651
TI  - Cloning and sequencing of a gene encoding D-aminoacylase from Alcaligenes
      xylosoxydans subsp. xylosoxydans A-6 and expression of the gene in Escherichia
      coli.
AB  - The gene encoding the D-aminoacylase of Alcaligenes xylosoxydans subsp.
      xylosoxydans A-6 (Alcaligenes A-6) was cloned and its complete nucleotide
      sequence was identified. The D-aminoacylase structural gene consists of 1452
      nucleotides and encodes 484 amino acid residues. The molecular weight of D
      aminoacylase was calculated to be 51,918. This value agreed well with the
      apparent molecular weight of 52,000 found for the purified enzyme from
      Alcaligenes A-6 by sodium dodecyl sulfate (SDS)-polyacrylamide gel
      electrophoresis (PAGE). The N-terminal amino acid sequence (NH2-SQSDSQPFDLLRAG-)
      predicted by the nucleotide sequence exactly matched those of the purified D
      aminoacylase both from Alcaligenes A-6 and from cloned Escherichia coli (E.
      coli), with the exception of the removal of the N-terminal methionine processed
      after translation. The purified recombinant enzyme showed almost the same
      enzymatic properties as the native enzyme from Alcaligenes A-6. Alcaligenes A-6 D
      aminoacylase showed 25-29% homology with L-aminoacylases from Bacillus
      stearothermophilus, porcine and humans.

PMID- 8541652
TI  - Effects of adrenalin on the conversion ratio of tryptophan to niacin in rats.
AB  - The administration of glycemia-affecting chemicals such as alloxan,
      streptozotocin, and 6-aminonicotinamide decreases the conversion ratio of
      tryptophan to niacin. Adrenalin is also known to increase the glucose level. For
      this reason, the effects of adrenalin on the conversion ratio were investigated.
      We found that the conversion ratio of tryptophan to niacin was reduced to half by
      the intraperitoneal injection of adrenalin at 75 micrograms/day/rat (body weight,
      about 250 g) every day for 7 days. Niacin decreases adrenalin-stimulated
      glycogenolysis via stimulating phosphodiesterase activity or depressing adenyl
      cyclase activity. Accordingly, in urgent need of energy, animals would have to
      decrease the concentration of niacin within the body.

PMID- 8541653
TI  - Relationship between molecular weights of pectin and hypocholesterolemic effects
      in rats.
AB  - Hypocholesterolemic activities and other properties of three different molecular
      weight pectin were examined. The low-molecular-weight pectin (M(r) not equal to
      66,000) obtained by decomposition of original pectin (M(r) not equal to 750,000)
      had the properties of low viscosity and high solubility, but it lost
      hypocholesterolemic activities in rats. On the other hand, the medium-molecular
      weight pectin (M(r) not equal to 185,000) had characteristics of both low
      viscosity and hypocholesterolemic activities.

PMID- 8541654
TI  - Substrate specificity of alpha-L-arabinofuranosidase from Bacillus subtilis 3-6
      toward arabinofurano-oligosaccharides.
AB  - The substrate specificity of alpha-L-arabinofuranosidase (EC 3.2.1.55) from
      Bacillus subtilis 3-6 was explored using methyl 2-O-, methyl 3-O-, and methyl 5-O
      alpha-L-arabinofuranosyl-alpha-L-arabinofuranosides, and methyl 3,5-di-O-alpha-L
      arabinofuranosyl-alpha-L-arabinofuranoside. The enzyme hydrolyzed the methyl
      alpha-L-arabinofuranobiosides to arabinose and methyl alpha-L-arabinofuranoside
      in the order of (1-->2)- > (1-->3)- > (1-->5)-linkages. The enzyme hydrolyzed the
      (1-->3)-linkage more than the (1-->5)-linkage of the methyl alpha-L
      arabinofuranotrioside.

PMID- 8541655
TI  - Effects of a component of green tea on the proliferation of vascular smooth
      muscle cells.
AB  - The effects of a component of green tea on the proliferation of smooth muscle
      cells were measured in terms of [3H]thymidine uptake. When green tea tannin
      mixture was added to the medium of cultured smooth muscle cells, it suppressed
      the proliferation of the cells dose-dependently. Similarly to the effects of the
      green tea tannin mixture, (-)-epigallocatechin 3-O-gallate, its main ingredient,
      had an inhibitory effect on smooth muscle cell proliferation at a low
      concentration. (-)-Epicatechin 3-O-gallate was also an effective component. Among
      four types of gallate-free tannin, (-)-epigallocatechin, (-)-epicatechin, and (+)
      catechin showed significant dose-dependent inhibition of smooth muscle cell
      proliferation. However, caffeine and theanine were found to have no such action.

PMID- 8541656
TI  - Trehalase activity and trehalose content in a freeze-tolerant yeast, Torulaspora
      delbrueckii, and its freeze-sensitive mutant.
AB  - Two types of trehalase activities different in the optimum reaction pH (4.3 and
      6.7) were found in a freeze-tolerant yeast, Torulaspora delbrueckii D2-4, and
      three types of the activities at pH 4.3, 5.7, and 6.7 were found in its freeze
      sensitive mutant (60B3). The pH 4.3 activities in the cell extracts of the two
      strains were on the same level, but the pH 6.7 activity in the strain D2-4 was
      about half of that in the strain 60B3. The enzyme with the pH 4.3 activity and
      the other two enzymes were analogous to acid and neutral trehalases,
      respectively, in the sensitivity to metal ions and in response to phosphorylation
      and dephosphorylation. The trehalose content in the strain D2-4 was three times
      higher than that in the strain 60B3. The change of trehalose content during
      growth of the strain 60B3 correlated only to the change of the pH 5.7 activity.

PMID- 8541657
TI  - Synthesis of novel oligosaccharides from leucrose by an alpha-glucosidase.
AB  - An alpha-glucosidase was purified in an electrophoretically pure state from an
      extract of koji culture of Aspergillus sp. KT-11. This enzyme was found to have a
      transferring activity when the reaction was done in a high concentration of
      leucrose at pH 4.5. Two kinds of transfer products, fractions I and II, were
      obtained from leucrose by the enzyme and they were identified as [(alpha-D
      glucopyranosyl-(1-->6)-alpha-D-glucopyranosyl-(1-->6)-alpha-D- glucopyranosyl-(1-
      >5)-D-fructopyranose] and [alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosyl
      (1-->5)-D- fructopyranose], respectively. These are considered to be novel
      oligosaccharides.

PMID- 8541658
TI  - Bacillus subtilis strains carry highly homologous direct repeat sequences on
      their chromosomes.
AB  - Highly homologous 170-bp sequences were found to be carried in the same
      orientation by the chromosomes of Bacillus subtilis GSY908 (a 168 derivative), B.
      subtilis R, and B. subtilis var. natto. These sequences were in 5'- and 3'
      flanking regions of a tetracycline-resistance determinant in B. subtilis GSY908
      and B. subtilis R.

PMID- 8541659
TI  - Assessment of the mutagenicity of extracts of TMV-coat-protein-gene induced
      transgenic tomato by the umu-test.
AB  - We examined the mutagenicity of extracts (juice and ethanol extract) from a
      transgenic tomato that was established by transfection of a gene encoding the
      coat protein of tobacco mosaic virus (TMV) to the F1 hybrid between Lycopersicon
      esculentum LA1000 and L. peruvianum PI128650, by the umu-test with Salmonella
      typhimurium TA1535/pSK1002 as the test organism. The extracts showed no
      detectable mutagenicity. The extracts from the above-mentioned F1 hybrids and
      wild tomatoes and cultivars (L. peruvianum PI128650, L. peruvianum PI126944, L.
      pimpinellifolium LS1524, L. pimpinellifolium LA722, L. hirsutum LS503, Mini
      carol, Sun-cherry, Momotaro, Odoriko, Kagome77, and Ponderosa) also showed no
      detectable mutagenicity.

PMID- 8541660
TI  - Purification and some properties of six chitinases from Aeromonas sp. no. 10S-24.
AB  - Six chitinases were purified from a culture supernatant of Aeromonas sp. no. 10S
      24 by ammonium sulfate precipitation, DEAE-Sephadex A-50, Butyl-Toyopearl 650M,
      and chromatofocusing. These enzymes were most active at pH 3.5-4.5 and the
      optimum temperature were 50 degrees C. The molecular weights of the enzymes were
      89,000 to 120,000 from SDS-polyacrylamide gel electrophoresis. N-Terminal amino
      acid sequences of the enzymes were similar to that of chitinase I.

PMID- 8541661
TI  - Application of the upstream region of a Bacillus endoglucanase gene to high-level
      expression of foreign genes in Bacillus subtilis.
AB  - A 0.4-kb ScaI-HpaI fragment, 199 bp upstream of the structural gene for alkaline
      endoglucanase, from the alkalophilic Bacillus sp. KSM-64, was found to be
      essential for the extracellular production of the enzyme by recombinant Bacillus
      subtilis cells. We constructed a new vector, pHSP64 (5.5 kb), using pHY300PLK and
      part of the 5' region of the endoglucanase that contained a possible promoter
      region. Using recombinant B. subtilis cells that carried this vector, very high
      production of two endoglucanases and of chloramphenicol acetyltransferase was
      done.

PMID- 8541662
TI  - Optical resolution of 1-arylethanols with a condensed aromatic ring by lipase
      from Pseudomonas aeruginosa.
AB  - Enantioselective syntheses of both enantiomers of 1-arylethanols with a condensed
      aromatic ring have been done through acetylation of the racemic alcohols with
      vinyl acetate in the presence of a lipase from Pseudomonas aeruginosa (Toyobo,
      LIP). The lipase LIP showed high enantioselectivity and reactivity for the title
      compounds, reacted acetates, and remaining alcohols were obtained with high
      optical purity.

PMID- 8541663
TI  - Cloning and nucleotide sequence of a leaf ferredoxin-nitrite reductase cDNA of
      rice.
AB  - A ferredoxin-nitrite reductase (EC 1.7.7.1) cDNA was isolated and sequenced from
      a lambda gt 11 cDNA library constructed from nitrate-induced greening shoots of
      rice (Oryza sativa L.) seedlings. The nucleotide sequence of the cDNA clone
      contains an open reading frame of 1788 nucleotides. There exists a strong bias
      for the third codon usage of G/C (95.5%) as in the case of the maize enzyme. The
      deduced amino acid sequence shows an overall homology to the maize (81%) and the
      dicot enzymes (70-74%), suggesting that the primary structure of ferredoxin
      nitrite reductase is highly conserved in higher plants.

PMID- 8541664
TI  - Increase in the level of mRNA for 3-hydroxyanthranilate 3,4-dioxygenase in brain
      of epilepsy-prone El mice.
AB  - We had shown that production of quinolinic acid is high in the brain of epilepsy
      prone El mice and that this is due to an increase in the activity of 3
      hydroxyanthranilate 3,4-dioxygenase (3-HAO, EC 1.13.11.6). We demonstrated here
      that the level of mRNA for 3-HAO was markedly increased in the brain of El mice.

PMID- 8541665
TI  - Sterilization with methyl cyanoacrylate-induced fallopian tube occlusion from a
      nonsurgical transvaginal approach in rabbits.
AB  - PURPOSE: To evaluate a nonsurgical, nonhormonal sterilization procedure performed
      with use of transvaginal microcatheterization techniques and methyl cyanoacrylate
      (MCA) as a sclerosing agent MATERIALS AND METHODS: Seventeen adult virgin female
      rabbits underwent bilateral fallopian tube cannulation through a nonsurgical
      transvaginal approach with use of a coaxial catheter system with fluoroscopic
      guidance. Fourteen of the rabbits underwent bilateral fallopian tube occlusion
      with direct MCA injection; the remaining three rabbits were separated as
      controls. Three of the rabbits with occlusions were killed as temporal histologic
      controls. The remaining 11 rabbits with occlusions and the initial three controls
      underwent 6 months of mating trials. All 17 rabbits were killed. Gross inspection
      was performed and histologic specimens of their fallopian tubes were obtained.
      RESULTS: None of the 11 rabbits with occlusions that underwent mating became
      pregnant. All three control rabbits became pregnant. Histologic examination of
      the occluded fallopian tubes demonstrated long-segment tubal wall fibrosis with
      varying degrees of occlusion. No peritoneal abnormalities were identified.
      Histologic findings for the three control animals were normal. CONCLUSION: With
      use of a nonsurgical transcervical coaxial catheter system, MCA can be placed
      directly into fallopian tubes without difficulty. MCA administration leads to
      fallopian tube fibrosis and occlusion. A 100% nonpregnancy rate was demonstrated.
      Further investigation may lead to a safer, more convenient, and less expensive
      form of permanent sterilization.

PMID- 8541666
TI  - Percutaneous creation of arteriovenous hemodialysis grafts: work in progress.
AB  - PURPOSE: To develop a technique of percutaneous creation and/or revision of
      arteriovenous hemodialysis access grafts, and to study the feasibility of the
      technique in the acute setting. MATERIALS AND METHODS: Arteriovenous shunts,
      consisting of silicone-covered Wallstents 6 (n = 10) or 8 (n = 1) mm in diameter
      and 11-17 cm in length, were created in 10 mongrel dogs. All shunts were created
      percutaneously except one, in which the carotid artery was exposed surgically and
      the jugular vein accessed percutaneously to create a straight external graft. All
      other grafts were femoral loops (femoral artery to femoral vein). Eight were
      tunneled subcutaneously and three were left external. All shunts were delivered
      through 10-F peel-away sheaths. RESULTS: The 11 shunts were allowed to flow for a
      mean of 4 hours (range, 1.0-6.5 hours) before the animals were killed. Leakage
      around the "anastomoses" was not observed. Leaks in the silicone covering were
      observed, resulting in one early shunt failure. Two attempted survival
      experiments were aborted due to early shunt dislodgment at 1.5 and 3.5 hours.
      CONCLUSIONS: Percutaneous arteriovenous shunt creation is feasible through
      acceptably small sheaths. Peel-away sheath placement of the stent circumvents the
      technical problem of placing a closed device into both artery and vein. This
      technique may allow percutaneous revision of existing hemodialysis access grafts
      and possibly de novo creation of grafts in humans, but modification of the grafts
      will be needed to prevent dislodgment.

PMID- 8541667
TI  - Pulmonary embolism following hemodialysis access thrombolysis/thrombectomy.
AB  - PURPOSE: The increased use of thrombectomy with deliberate pulmonary embolization
      of thrombus following initial thrombolysis for occluded hemodialysis fistulas
      prompted the authors to measure the prevalence of pulmonary embolism (PE) due to
      the procedure. PATIENTS AND METHODS: Thirty-one patients with 43 acutely
      thrombosed polytetrafluoroethylene hemodialysis fistulas were treated with
      thrombolysis/thrombectomy. Perfusion lung scans were obtained in 22 patients.
      Patients were also continuously monitored for clinical signs or symptoms of PE.
      RESULTS: Perfusion scans were interpreted as consistent with PE in 59% of those
      studied, but no clinical signs or symptoms were present in 41 of the 43 cases
      (95%). However, two patients developed both signs and symptoms of acute PE in the
      postprocedural period and died. One had underlying pulmonary disease and had
      undergone thrombectomy before. The other had chronic heart disease. CONCLUSION:
      Thrombolysis/thrombectomy is usually safe and effective, even though many
      patients develop subclinical PE. The authors urge extreme caution in patients who
      have underlying pulmonary or cardiac disease and/or have undergone the procedure
      before.

PMID- 8541668
TI  - Transjugular intrahepatic portosystemic shunt placement for variceal bleeding:
      predictors of mortality.
AB  - PURPOSE: To identify factors that predict survival in patients with variceal
      bleeding who have undergone transjugular intrahepatic portosystemic shunt (TIPS)
      placement. PATIENTS AND METHODS: TIPS was performed in 64 of 65 patients.
      Indications were bleeding esophagogastric varices in 64 patients and hemorrhoidal
      bleeding in one. Child-Pugh classifications were A in two patients, B in 32, and
      C in 31. Acute bleeding was controlled before TIPS in 26 patients in stable
      condition but not in 39 patients whose condition was unstable. RESULTS: Twelve
      patients died within 30 days of TIPS, and another 14 died thereafter. The
      cumulative survival rate was 67% at 6 months and 56% at 1 year. Cumulative 30-day
      survival was 96% for stable and 69% for unstable patients, a significant
      difference (P = .0135). Thirty-day survival was 91% for patients in Child-Pugh
      classes A and B combined and 71% for patients in class C (P = .042). CONCLUSION:
      Efforts to control acute bleeding and improve a patient's metabolic status before
      TIPS are likely to improve 30-day survival.

PMID- 8541669
TI  - Liver transplantation complicated by malpositioned transjugular intrahepatic
      portosystemic shunts.
AB  - PURPOSE: To report the surgical problems encountered during orthotopic liver
      transplantation as a result of a malpositioned transjugular intrahepatic
      portosystemic shunt (TIPS). PATIENTS AND METHODS: Three patients are described in
      whom TIPS stents were malpositioned in the following locations: extending into
      the main portal vein, extending into the suprahepatic inferior vena cava, and
      extending into the right atrium. RESULTS: Malpositioning of TIPS stents altered
      and prolonged the operation in all of these patients by interfering with cross
      clamping at the usual vascular sites during liver transplantation. Incorporation
      of the stents into the vascular wall prevented transcatheter retrieval and
      increased the difficulty of intraoperative removal. CONCLUSION: Awareness of
      hepatic vascular anatomy is necessary in avoiding stent malpositioning. If
      malpositioning is identified, transcatheter approaches may be helpful in
      repositioning the stent. Otherwise, the transplant surgery team must be made
      aware of the problem for proper surgical planning prior to liver transplantation.

PMID- 8541671
TI  - Recanalization of the superior mesenteric vein for massive bleeding in Crohn
      disease.

PMID- 8541670
TI  - Effect of spontaneous splenorenal shunts on portal hemodynamics: limited
      regression of varices after transjugular intrahepatic portosystemic shunt
      creation.

PMID- 8541672
TI  - Transjugular transhepatic placement of a superior mesenteric vein stent for small
      bowel varices.

PMID- 8541673
TI  - Access systems for puncture at an acute angle.

PMID- 8541674
TI  - Severity of disease score as a predictor of mortality after caval filter
      insertion.
AB  - PURPOSE: To estimate 30-day mortality after vena caval filter insertion and
      assess the usefulness of a severity of disease score in predicting postprocedure
      30-day survival. PATIENTS AND METHODS: Records of 40 consecutive patients
      undergoing inferior vena caval filter insertion over a 2 1/2-year period were
      retrospectively reviewed. A severity of illness score for each patient was
      calculated based on the weighting system described for the APACHE (Acute
      Physiology and Chronic Health Evaluation) II system. In addition, 30-day
      postprocedure survival was determined. RESULTS: Seven patients died within 30
      days of the procedure (18%). The use of a severity of disease score of greater
      than 15 as a predictor of postprocedure 30-day mortality had a sensitivity of
      50%, specificity of 97%, positive predictive value of 75%, a negative predictive
      value of 91.4%, and accuracy of 90%. CONCLUSIONS: The 30-day mortality after
      caval filter insertion is significant. A severity of disease score is a useful
      predictor of patients likely to survive following caval filter insertion. On this
      basis it may be possible to establish criteria for more beneficial use of vena
      caval filters.

PMID- 8541675
TI  - Prospective anatomic study of the inferior vena cava and renal veins: comparison
      of selective renal venography with cavography and relevance in filter placement.
AB  - PURPOSE: To compare the sensitivity of selective renal venography with that of
      cavography in the detection of variant anatomic structures of the renal vein that
      may affect the placement of inferior vena caval (IVC) filters and to define IVC
      dimensions. PATIENTS AND METHODS: Flush cavography, selective bilateral renal
      venography, and bilateral iliac venography were performed in 108 patients
      referred for IVC filter placement or vena cavography. Infrarenal IVC length and
      width were determined with a sizing catheter during cavography. Anomalies were
      considered significant if they altered placement or selection of the vena cava
      filter or if they represented a potential collateral pathway for clot to bypass a
      filter. RESULTS: Variant anatomic structures in the renal vein were found in 11%
      of patients with cavography and in 37% of patients with selective renal vein
      injection. Detected anomalies included circumaortic veins (n = 11), multiple
      veins (n = 25), retroaortic veins (n = 2), and a partially duplicated IVC (n =
      1). Selective venography depicted anomalies not suspected at standard cavography
      in 28 cases (26%); in 20 cases (18% of population) they were significant. The
      average infrarenal width was 20 mm on the anteroposterior view and was 17 mm on
      the lateral projection. CONCLUSION: IVC anomalies are common, and selective renal
      venography can depict significant anomalies in renal vein anatomic structures not
      shown at standard cavography.

PMID- 8541676
TI  - Temporary inferior vena cava filters: in vitro comparison with permanent IVC
      filters.
AB  - PURPOSE: An in vitro comparison of clot-trapping abilities of permanent and
      temporary inferior vena cava (IVC) filters. MATERIALS AND METHODS: A flow model
      was used to simulate the IVC. Two permanent IVC filters, the titanium Greenfield
      and LG-Medical (LGM), were compared with two temporary filters, the Filcard
      International and Gunther. Clot sizes used were 2.5 x 2.5 mm, 2.5 x 5 mm, 5 x 5
      mm, 5 x 10 mm, and 5 x 20 mm. Individual clots were presented to the filters with
      the simulated IVC in a horizontal or vertical orientation. Clot-trapping dynamics
      and pressure gradient changes during the injection of multiple, sequential clots
      were also examined. RESULTS: As clot size diminished, all filters trapped fewer
      clots; however, the temporary filters trapped more small clots than the permanent
      filters. Very little difference was observed in clot-trapping abilities among the
      filters for clots of 5 x 10 mm or greater. In the horizontal orientation, the
      permanent filters trapped 38% of all clots delivered, while the temporary filters
      trapped 73%, chi 2 = 24.8 (P < .001). In the vertical orientation, the overall
      clot-trapping abilities of the filters improved, with the permanent filters
      trapping 73% of all clots delivered, while the temporary filters trapped 95%, chi
      2 = 18 (P < .001). During trapping of multiple clots, the temporary filters
      allowed fewer clots to pass. CONCLUSION: The temporary filters performed better
      than the permanent filters in both individual clot-trapping orientations. During
      multiple clot-trapping experiments, fewer clots were allowed to pass by the
      temporary filters. The temporary filters demonstrated the ability to capture
      clots both inside and outside the wire struts.

PMID- 8541677
TI  - Use of a temporary caval filter to assist percutaneous iliocaval thrombectomy:
      experimental results.
AB  - PURPOSE: To test a new filter design that allows coaxial insertion of
      thrombectomy devices and active clot removal. MATERIALS AND METHODS: A prototype
      filter system was used in animal experiments. It is a transjugularly inserted
      coaxial system with a 16-F outer sheath and an inner tube that is covered by a
      tulip-shaped meshwork with a 22-mm diameter at its inserted end. The inner tube
      allows insertion of instruments up to 8 F. The filter was developed to assist
      with percutaneous mechanical thrombectomy in the iliofemoral and caval veins. The
      filter has been used as an assisting tool in nine sheep and eight pigs. It was
      combined with an impeller system in nine sheep for caval thrombectomy and with a
      hydrodynamic catheter for iliac thrombectomy in eight pigs after artificial
      induction of iliac or caval thrombosis. RESULTS: The filters captured emboli from
      the intervention in six of nine sheep. The amount of captured emboli was reduced
      within the filter cone by the impeller instrument in five of six instances.
      Residual thrombus was removed by closing the filter in five of six sheep. In
      pigs, the filter captured emboli in three cases during hydrodynamic embolectomy.
      Pulmonary embolization did not occur with the filter in place. After filter
      removal, minor pulmonary clot embolization occurred in one case. CONCLUSION: The
      temporary tulip filter was effective in these animal models in capturing and
      removing thrombus material that may dislodge from iliocaval veins during
      mechanical thrombectomy.

PMID- 8541679
TI  - Treatment of malignant esophageal obstructions with covered metallic Z stents:
      long-term results in 52 patients.
AB  - PURPOSE: To prospectively evaluate the clinical efficacy of silicone-covered
      Gianturco-Rosch self-expandable Z (GRZ) stents in the treatment of malignant
      esophageal obstruction. PATIENTS AND METHODS: GRZ stents were placed in 52
      patients (39 men, 13 women) with severe dysphagia due to high-grade malignant
      esophageal obstruction. RESULTS: Stent placement was technically successful, and
      immediate relief of dysphagia was achieved in 50 of 52 patients (96%), with long
      term relief in 47 patients (90%). Fifty-one patients (98%) died during follow-up
      (range, 1 week to 33 months; mean, 4.3 months). Late complications were most
      prevalent and included stent migration (n = 5), food impaction (n = 2), chest
      pain (n = 2), membrane disruption with tumor ingrowth (n = 1), granulomatous
      reaction above the stent (n = 1), esophageal perforation with mediastinitis (n =
      1), and upper gastrointestinal hemorrhage (n = 4). Twelve complications were
      easily managed with medical, endoscopic, or radiologic intervention. Four deaths
      may have been related to stent placement (early mortality rate, 7.7%).
      CONCLUSION: GRZ stents provide relatively safe and effective long-term palliation
      in patients with severe, malignant esophageal obstruction.

PMID- 8541678
TI  - Boerhaave syndrome: to treat or not to treat by means of insertion of a metallic
      stent.

PMID- 8541680
TI  - Metallic stents for the treatment of intrahepatic biliary strictures after liver
      transplantation.
AB  - PURPOSE: The authors report their results with use of metallic stents for the
      treatment of intrahepatic biliary strictures occurring after liver
      transplantation. PATIENTS AND METHODS: Twenty-four patients with intrahepatic
      biliary strictures after liver transplantation were treated with metallic stents.
      Eleven had undergone prior unsuccessful percutaneous balloon dilation. Successful
      stent deployment occurred in all subjects. Gianturco, Wallstents, and Palmaz
      stents were used. Follow-up was obtained in all 24 patients. RESULTS: Initial
      technical success was obtained in all 24 patients. In 11 patients, long-term
      primary, primary assisted, or secondary stent patency was achieved with follow-up
      ranging from 17 to 58 months. Ten patients died or underwent retransplantation
      within 14 months for reasons unrelated to their stents. In three patients, stent
      placements failed because of stent obstructions that were refractory to attempts
      at secondary patency. By life-table analysis, cumulative primary, primary
      assisted, and secondary patency rates were 50%, 61%, and 80%, respectively, at 18
      months. CONCLUSION: Metallic biliary stents offer promising results for
      intrahepatic strictures in the posttransplant patient, particularly in patients
      with widespread strictures. Stents can become partially or totally obstructed due
      to sludge and debris, but patency can often be restored with additional
      interventional techniques.

PMID- 8541681
TI  - Percutaneous ablation of a pancreatic remnant with intraductal injection of
      neoprene.

PMID- 8541682
TI  - Management of large high-flow arteriovenous malformations of the shoulder and
      upper extremity with transcatheter embolotherapy.
AB  - PURPOSE: To evaluate the efficacy of transcatheter embolization of arteriovenous
      malformations (AVMs) of the shoulder and upper extremity. PATIENTS AND METHODS:
      Four men with large AVMs of the shoulder and upper extremity were treated with
      transcatheter arterial embolization. Symptoms included high cardiac output, pain,
      paresthesias, and disfigurement. Each patient underwent multiple sessions of
      embolotherapy. RESULTS: In two patients there was no decrease in cardiac output.
      In three patients, no permanent decrease in AVM size or resolution of pain was
      achieved. Two patients experienced postembolization skin necrosis, and one
      experienced permanent radial neuropathy. CONCLUSIONS: Large, high-flow AVMs in
      the shoulder and upper extremity may be relatively refractory to intravascular
      treatment because of the diffuse involvement of the soft tissues by the AVM and
      the lack of a well-defined nidus. Transcatheter embolotherapy in these lesions
      should be reserved for patients undergoing resection to help decrease
      intraoperative bleeding.

PMID- 8541683
TI  - Thrombolytic therapy compared with mechanical recanalization in non-acute
      peripheral arterial occlusions: a randomized trial.
AB  - PURPOSE: To evaluate whether thrombolytic therapy followed by angioplasty has any
      added benefit compared with angioplasty alone for the treatment of chronic
      peripheral arterial occlusions. PATIENTS AND METHODS: Twenty patients with
      claudication or limb-threatening ischemia of at least 3 weeks duration due to
      iliac or femoropopliteal artery occlusions were randomized either to thrombolytic
      therapy with recombinant tissue-type plasminogen activator for up to 4 hours (n =
      11) followed by angioplasty or to angioplasty alone (n = 9). Clinical follow-up
      was obtained for 1 year. RESULTS: Life-table analysis revealed a significant
      improvement in the cumulative primary patency rate for patients with claudication
      treated initially with thrombolysis followed by angioplasty (n = 7; 86% at 6
      months; 51% at 1 year) compared with angioplasty alone (n = 9; 11% at 6 months
      and 1 year) (P < .02). All four patients with limb-threatening ischemia were
      randomized to thrombolytic therapy, and none exhibited continued patency at 1
      year. The most common complication in the thrombolysis group was peripheral
      embolization; three of these four patients were among those who had limb
      threatening ischemia as the indication for entry into this study. There was no
      increased incidence of bleeding with thrombolytic therapy. CONCLUSIONS: A short
      course of thrombolytic therapy prior to angioplasty appears to improve the 1-year
      patency rate for claudication due to iliac or femoropopliteal occlusions.
      However, patients with limb-threatening ischemia have a high prevalence of
      peripheral embolization and dismal patency rates with this form of therapy. A
      larger scale study is necessary to confirm these findings.

PMID- 8541684
TI  - Intraarterial thrombolysis of a deep femoral-posterior tibial venous conduit via
      direct infragenicular graft puncture.

PMID- 8541685
TI  - Angioplasty for the treatment of visceral ischemia.
AB  - PURPOSE: To evaluate percutaneous transluminal angioplasty (PTA) in the treatment
      of visceral ischemia. PATIENTS AND METHODS: Over a 14-year period, 25 focal
      visceral artery stenoses were treated with PTA in 16 patients with acute or
      chronic visceral ischemia. Thirteen patients were women and three were men, with
      a mean age of 64.7 years (range, 54-79 years). PTA was performed in seven celiac
      arteries, 17 superior mesenteric arteries, and one inferior mesenteric artery.
      RESULTS: PTA was technically successful in 14 of 16 patients (88%). Two patients
      were lost to follow-up. Nine of 12 patients (75%) demonstrated primary patency
      with relief of clinical symptoms at a mean follow-up of 2.3 years (range, 0.3-5
      years). The remaining three patients underwent successful repeat PTA for
      recurrent symptoms. There was one postprocedural death, and one patient
      subsequently underwent successful surgical bypass for recurrent visceral
      ischemia. CONCLUSIONS: Angioplasty of the visceral arteries may provide relief
      for select patients with intestinal ischemia, but redilation may be required in
      some patients.

PMID- 8541686
TI  - Treatment of hemobilia with selective hepatic artery embolization.
AB  - PURPOSE: To evaluate retrospectively the results of selective transcatheter
      embolization in the treatment of hemobilia. PATIENTS AND METHODS: Twelve patients
      with hemobilia (mean age, 43 years) underwent embolotherapy. Causes of hepatic
      vascular injury were iatrogenic trauma, blunt external trauma, septic emboli, and
      lupus vasculitis. A 5-F cobra catheter or a 5-F non-tapered Simmons shaped
      catheter passed over a hydrophilic guide wire, or a Tracker 18 catheter forming a
      coaxial system was used. Embolic agents included gelatin sponge or polyvinyl
      alcohol fragments used alone or with coils. RESULTS: Hepatic artery
      pseudoaneurysms were found in 10 patients, ruptured hepatic artery aneurysm was
      found in one, and arterioportal fistula was found in two (with pseudoaneurysm in
      one). Bleeding was immediately controlled in 11 of 12 patients after
      embolization; one patient rebled and underwent surgery. Two patients underwent
      repeat embolization (2 weeks and 2 months later). Two patients died, one of
      biliary sepsis and liver insufficiency 24 hours after embolization and the other
      of gangrenous cholecystitis. CONCLUSION: Transcatheter embolization is an
      effective treatment of hemobilia. It allows control of bleeding and
      identification of the origin of the hemorrhage.

PMID- 8541687
TI  - Percutaneous removal of a misplaced Palmaz stent with a coaxial snare technique.

PMID- 8541688
TI  - Endovascular stent-graft repair of common iliac artery-to-inferior vena cava
      fistula.

PMID- 8541689
TI  - Blood back flow into angiographic catheters.
AB  - PURPOSE: Because of a potential impact on thrombus formation, this study
      determines the degree of blood back flow into catheters filled with different
      fluids. MATERIALS AND METHODS: Catheters filled with saline or non-ionic or ionic
      contrast medium were placed in pulsatile circulating human blood in vitro.
      Catheter orientation was varied, and blood back flow was recorded. RESULTS: When
      the leading end of the catheter was angled downward, blood back flow into a
      contrast material-filled catheter was far greater than that into a saline-filled
      catheter (7.0 vs 0.5 cm). Conversely, when the leading end of the catheter was
      horizontal, blood back flow was much greater when the catheter contained saline
      versus contrast media (3.6 vs 0.4 cm). Ionicity of contrast material did not
      affect back flow. CONCLUSION: Back flow of blood into a catheter can be
      considerable and is dependent on the type of fluid within the catheter and
      orientation of the leading end of the catheter. Angiographic techniques adjusted
      to these findings are important to maintain patient safety.

PMID- 8541690
TI  - Ca2+ and cyclic adenosine monophosphate involvement in radiographic contrast
      medium-induced renal vasoconstriction.
AB  - PURPOSE: To investigate the role of extracellular Ca2+ and cyclic 3'-5' adenosine
      monophosphate (cAMP), a known second messenger promoting smooth muscle
      relaxation, in preventing renal vasoconstriction induced by radiographic contrast
      medium (RCM). MATERIALS AND METHODS: Isometric contractions of rabbit renal
      artery were elicited by potassium chloride and increasing concentrations of
      meglumine/sodium diatrizoate. To determine the contribution of extracellular
      Ca2+, nifedipine, a blocker of voltage-dependent L-type Ca2+ channels (VDCC), was
      applied. The contribution of cAMP was investigated by applying the nonspecific
      phosphodiesterase (PDE) inhibitors papaverine and theophylline and the specific
      PDE inhibitor milrinone, all of which prevent degradation of cAMP. Forskolin, an
      activator of cAMP by stimulating adenylyl cyclase (AC), was also investigated.
      RESULTS: RCM elicited contractions that were 24.5% of the KCl control
      contraction, which was reduced by nifedipine (100 mumol/L) by 34.7%. Papaverine,
      theophylline, and milrinone inhibited RCM-induced contractions by 69.8%, 64.3%,
      and 43.7%, respectively. Forskolin reduced the response by 82.2%. CONCLUSION:
      Ca2+ influx through VDCC partially contributes to RCM-induced renal artery
      vasoconstriction. Intracellular cAMP appears to be an important second messenger
      pathway for prevention of this response. These findings emphasize the role of
      second messenger systems involved in adverse RCM effects and the potential
      prevention of these effects.

PMID- 8541691
TI  - Complement activation by angiographic catheters in vitro.
AB  - PURPOSE: Four different polymers used in commercial angiographic catheters were
      compared in vitro with respect to their ability to activate the complement
      system. MATERIALS AND METHODS: Commercially available angiographic catheters made
      from one of the following plastics were used: polyamide, polyethylene,
      polyurethane, and polytetrafluoroethylene. Silicone-coated latex urinary
      catheters served as the reference standard. Each catheter was cut into 20-mm
      segments, immersed in a polypropylene tube containing fresh serum from a
      volunteer donor, and incubated at 37 degrees C. Samples were drawn at 15 minutes,
      1 hour, and 6 hours; C3 activation products (C3AP) and the terminal complement
      complex (TCC) content were estimated with enzyme immunoassays. RESULTS: By 1
      hour, a significant increase in C3AP and TCC concentrations was observed with all
      angiographic catheters relative to controls (P < .01-.001). The time
      concentration plots for both C3AP and TCC were steepest for polyamide. C3AP
      concentrations relative to controls were significantly higher with exposure to
      polyamide compared with polyurethane at 1 hour (P < .01), and with both
      polyethylene and polyurethane at 6 hours (P < .01). Polytetrafluoroethylene
      induced larger amounts of C3AP formation by 6 hours than polyethylene and
      polyurethane (P < .05). However, polytetrafluoroethylene was associated with the
      lowest relative median concentrations of TCC; the difference with polyamide was
      significant at 6 hours (P < .001). As with C3AP, differences in TCC generation
      between polyethylene and polyurethane were marginal at all observation points (P
      > .05). CONCLUSIONS: All the polymers tested activated the complement system.
      Activation was most prominent with exposure to polyamide and least marked with
      polyurethane.

PMID- 8541692
TI  - Role of vascular and interventional radiology in the Oklahoma City bombing.

PMID- 8541693
TI  - Nutritional and metabolic considerations of the adult liver transplant candidate
      and organ donor.
AB  - Liver transplantation has progressed from an experimental procedure to an
      accepted treatment for end-stage liver disease. Yet, many potential recipients
      will die from infection, coagulopathy, or metabolic derangements before a donor
      liver becomes available. In addition, primary graft dysfunction after
      transplantation still represents a significant drain on professional resources.
      For these reasons, more attention is being directed toward identification of
      nutritional and metabolic factors in both the liver recipient and organ donor
      that can influence transplant outcome. The metabolic alterations present in these
      patients before and after liver transplantation require a more sophisticated
      approach to the provision of appropriate nutrition support. The goals of
      nutrition intervention for both the recipient and donor are to foster improved
      function of the allograft liver and to optimize eventual transplant outcome.

PMID- 8541694
TI  - Energy requirements in Alzheimer's disease patients.
AB  - Weight loss in Alzheimer's patients has been observed by many clinicians and
      reported in the international geriatric literature. It represents a puzzling
      challenge for clinicians and researchers, and it is an important issue for
      caregivers and nursing home staff concerned with state and federal requirements
      for nutrition and weight monitoring. Using indirect calorimetry, we studied the
      resting energy expenditure of 21 elderly patients; 12 were residing in a
      community setting, and 9 were institutionalized. Of the 12 community-living
      patients studied, 5 had early to moderate Alzheimer's disease, and 7 were
      nondemented control subjects. Of the 9 institutionalized patients, all were
      severely demented, bedridden, and fed exclusively by gastric tube in a closely
      monitored clinical environment with daily bedside weighing. Four had Alzheimer's
      disease, and 5 had multi-infarct dementia (MID). Among the outpatients, the
      Alzheimer's group showed increased energy requirements (p = 0.028) and a
      significantly different pattern of fat-free mass compared with control subjects
      (p = 0.031). These observations on community-residing elderly were consistent
      with, and extended by our findings on energy requirements of, the demented
      institutionalized patients. The calorie intake necessary for weight maintenance
      of the bedridden institutionalized patients was determined during their prolonged
      institutionalization. The presumed maintenance level of calorie intake was then
      verified during a 10 wk study. During the 10 wk, we documented no significant
      change in weight with constant energy intake. Compared with MID patients,
      Alzheimer's patients tended to weigh less (52.84 vs 56.4 kg; p = 0.20) but
      actually required more calories (1626 vs 1341 kcal, p < 0.011).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8541695
TI  - Metabolic effects of infusion of a structured-triglyceride emulsion in healthy
      subjects.
AB  - Structured-triglyceride (STG) emulsions may have beneficial effects compared with
      traditional emulsions. We infused equimolar doses of STG and long-chain fatty
      acid triglyceride (LCT; Intralipid 20%) emulsions for 6 h into eight healthy
      subjects. Six subjects were also infused with either a low or a high dose of the
      STG emulsion. Blood concentrations of triglycerides and glycerol increased dose
      dependently. In seven of the eight subjects the increase in serum triglyceride
      concentrations was greater during LCT infusion than during STG infusion. The
      molar ratio of medium- to long-chain fatty acids in the plasma after infusions of
      STG at medium and high rates was close to the compositional molar ratio of this
      emulsion (1:1), indicating that medium- and long-chain fatty acids were released
      at similar rates. During fat infusion there was a small but significant decrease
      in plasma glucose and a modest increase in serum beta-hydroxybutyrate
      concentrations but no hypoglycemia. Serum phospholipids increased significantly
      in all groups except the one receiving the low dose of STG. Plasma insulin, serum
      lactate, and serum cholesterol concentrations did not change. In conclusion, the
      capacity of healthy subjects to hydrolyze STG was at least as high as that to
      hydrolyze LCT. Plasma fatty acid profiles during fat infusions were similar to
      the fatty acid compositions of the infused emulsions.

PMID- 8541697
TI  - The use of a football helmet to secure a nasogastric tube.
AB  - We describe the case of a 83-yr-old diabetic woman who, during convalescence for
      treatment of hyperosmolar nonketotic diabetic coma, required nasogastric
      intubation for enteral feeding. Her course was complicated by delirium during
      which time she repeatedly removed the nasogastric tube. A football helmet was
      used to secure the feeding tube and prevent its premature removal. Thereafter
      nasogastric feeding was uncomplicated. We recommend the use of a football helmet
      in patients with delirium who repeatedly remove their nasogastric tubes.

PMID- 8541696
TI  - Efficacy of a mixture of medium-chain triglyceride (75%) and long-chain
      triglyceride (25%) fat emulsions in the nutritional management of multiple-trauma
      patients.
AB  - Ten severely injured patients who were admitted to the intensive care unit and
      who needed total parenteral nutrition (TPN) were randomly enrolled in a
      prospective double-blind study comparing two 20%-fat intravenous emulsions: one
      (MCT-LCT) containing a physical mixture of 75% medium-chain triglyceride (MCT)
      and 25% long-chain triglyceride (LCT) and another containing 100% LCT. TPN (30
      kcal.kg-1.day-1) was given continuously as amino acids (20% of energy) and
      glucose (50% of energy) over 7 days with the respective lipid emulsion (30% of
      energy) provided from 0800 to 1600 each day. Plasma substrate concentrations,
      nitrogen balance, resting energy expenditure, substrate net oxidation rates,
      whole-body lipolysis rates, and fatty acid reesterification rates were measured
      or calculated. Plasma concentrations of lipid metabolites (glycerol,
      triglycerides, and fatty acids) indicated rapid hydrolysis and efficient use of
      the MCT-LCT emulsion. Whole-body lipolysis rate decreased by 53% in the MCT-LCT
      group and by 34% in the LCT group. Net fat oxidation was greater and FFA
      reesterification less with MCT-LCT than with LCT, indicating more efficient and
      rapid fuel utilization in the post-traumatic period with the MCT-LCT emulsion. In
      critically ill patients dependent on intravenous nutrition, an MCT-LCT mixture
      may be useful as an obligate fuel and to limit net hepatic lipogenesis.

PMID- 8541698
TI  - Healthful new oil from macadamia nuts.
AB  - Fatty acid profiles were obtained for macadamia nut oil and several other cooking
      oils. Macadamia nut oil contained the highest level (79%) of monounsaturated
      fatty acids. Macadamia nut oil is low (4%) in the omega-6 fatty acid 18:2n-6 and
      saturated fatty acids. Fatty acid profiles for popcorn cooked in several oils
      were obtained for comparison because of public awareness and concern over high
      levels of saturated fat found in popcorn sold in theaters. The nutritional
      implications of using macadamia nut oil are discussed.

PMID- 8541699
TI  - Thiolprotease activity in skeletal and myocardial muscle and liver of fasted
      rats.
AB  - The activity of the thiolproteases, cathepsins B, H, and B + L, one of the most
      important groups of endoproteases, was measured in skeletal and myocardial muscle
      and liver of Sprague-Dawley rats submitted to fasts of different duration
      (control and 24, 48, and 72 h). After the fasting period, the animals were
      killed, and fresh tissue samples were collected. Enzyme activity was determined
      in vitro with the specific substrates Z-Arg-Arg-MCA for cathepsin B, Z-Phe-Arg
      MCA for cathepsin B + L, and Arg-MCA for cathepsin H. Results show different
      patterns in the organs studied: activity increased linearly in liver, decreased
      in myocardial muscle, and had no change in skeletal muscle. These results suggest
      that the expected alteration observed in proteolytic activity in fasted tissues
      is produced to a certain degree by changes in thiolprotease activity.

PMID- 8541700
TI  - Mild-to-moderate malnutrition and small intestine of young rhesus monkeys.
AB  - The effect of severe malnutrition and protein deficiency on small intestine has
      been documented, but the literature on the effect of mild-to-moderate protein
      energy malnutrition (PEM) on small intestine is scant. Mild-to-moderate PEM is
      most prevalent in India. Twenty-four young rhesus monkeys weighing 1.5-2.0 kg
      were divided into two groups, control and experimental. Mild-to-moderate PEM was
      induced in the experimental group by giving half of the required normal diet
      providing 2.42 g protein.kg-1.day-1 and 55 kcal.kg-1.day-1. Body weight, serum
      protein, and D-xylose were measured before starting the experiment, at PEM stage,
      and after rehabilitation. Experimental monkeys representing group I were killed
      after a 25-30% reduction in body weight along with control group 1 animals at 12
      wk. The rest of the experimental animals were rehabilitated for another 10-12 wk
      and killed along with their respective controls (control group 2). Brush-border
      membrane vesicles were prepared from three parts of the small intestine. Viable
      vesicles were used for the uptake of [U-14C]L-proline. Alkaline phosphatase and
      enterokinase were also measured. Uptake of L-proline amino acid and the activity
      of both enzymes were found to be decreased significantly in the PEM group; a D
      xylose test was abnormal. All animals recovered after rehabilitation. These
      results indicate that even mild-to-moderate malnutrition affects the absorptive
      and digestive capacity of the brush border of the small intestine, which reversed
      back on rehabilitation.

PMID- 8541701
TI  - Nucleoside-nucleotide mixture increases peripheral neutrophils in
      cyclophosphamide-induced neutropenic mice.
AB  - The importance of nucleotides and nucleosides in human nutrition has now become
      an area of intensive research and clinical interest. To determine any potential
      benefits of administering a nucleoside-nucleotide mixture (NNM) to
      cyclophosphamide (CPA)-induced neutropenic mice, we randomly assigned 20 BALB/c
      mice to two groups and fed them a nucleic-acid-free 20%-casein diet for 20 days.
      The mice were intraperitoneally administered NNM or saline daily from the onset
      of the experiment. On the 10th day of this treatment, the mice were
      intraperitoneally injected with CPA. Blood was collected retro-orbitally and
      differential counts of leucocytes were done on blood smears by counting
      microscopically on day 0 (before) and 1, 3, 5, 7, and 10 days after CPA
      injection. By the 7th and 10th days after CPA injection, respectively, the
      peripheral neutrophil number in the saline group was significantly lower compared
      with the neutrophil number in the NNM group (p < 0.05). Also in the NNM group,
      more clusters of matured neutrophils were observed compared with the saline
      group. These results suggest that NNM may stimulate the proliferation,
      differentiation, and maturation of neutrophils, and that NNM alone or in
      combination with other pharmacologic agents may be an important therapeutic agent
      in patients after chemotherapy, immunosuppressive therapy, and organ transplant.

PMID- 8541702
TI  - Pregnant woman with Crohn's disease maintained on oral hyperalimentation.

PMID- 8541703
TI  - Intestinal responses induced by enteral feeding.

PMID- 8541704
TI  - Nutrition and quality of life.

PMID- 8541705
TI  - Medium-chain triglycerides: a new frontier.

PMID- 8541706
TI  - The 1994 John M. Kinney International Award for nutrition and metabolism.
      Metabolic response to a high-lipid, high-nitrogen peripheral intravenous
      nutrition solution after major upper-gastrointestinal surgery: background.

PMID- 8541707
TI  - The evolving health care market.... Making the cuts.

PMID- 8541708
TI  - Do block grants threaten school meals?

PMID- 8541709
TI  - Simple linear regression and correlation, continued.

PMID- 8541710
TI  - Alcohol and breast cancer: is there a conclusion?

PMID- 8541711
TI  - Benefits of supplementary tube feeding after fractured neck of femur: a
      randomised controlled trial. 1983.

PMID- 8541712
TI  - Identification and analysis of Rh genes: application of PCR and RFLP typing
      tests.

PMID- 8541713
TI  - In vitro assays to predict the severity of hemolytic disease of the newborn.

PMID- 8541714
TI  - The introduction of human monoclonal anti-D for therapeutic use.

PMID- 8541715
TI  - Abnormal cellular immune mechanisms associated with autoimmune thrombocytopenia.

PMID- 8541716
TI  - Transfusion medicine issues in the practice of anesthesiology.

PMID- 8541717
TI  - Analysis of some operating parameters of novel adsorbents for recovery of
      proteins in expanded beds.
AB  - We have analysed some operational parameters for two novel adsorbents intended
      for recovery of proteins from particle-containing feedstocks using expanded bed
      adsorption. The adsorbents tested were STREAMLINE DEAE and STREAMLINE SP, ion
      exchangers based on an agarose/crystalline quartz composite. Parameters analysed
      included bed expansion, adsorption efficiency, washing and elution. Bed expansion
      was considerably lower for STREAMLINE adsorbents compared to conventional agarose
      based media, higher flow velocities were thus possible during the expanded bed
      process. Breakthrough capacity was 63 mg ml-1 for lysozyme on STREAMLINE SP and
      36 mg ml-1 for bovine serum albumin on STREAMLINE DEAE at a flow velocity of 300
      cm h-1. To achieve high breakthrough capacity, the sedimented bed height should
      be at least 10 cm. Furthermore, breakthrough capacity increased to some extent
      when temperature was increased from room temperature to 36 degrees C, a
      phenomenon which can be useful in some processes. The number of living E. coli
      cells in the effluent was reduced by a factor of 10(5) after washing with 15
      sedimented bed volumes. The optimal flow velocity for elution was 100 cm h-1
      considering time for elution and volume of the eluted fraction. Flow direction
      during elution in packed bed mode had little impact on the elution volume,
      however, elution in expanded bed mode increased the volume by approx. 40%. The
      data presented on the performance of STREAMLINE adsorbents show that they are
      very useful for recovery of proteins from particle-containing feedstocks using
      expanded bed adsorption.

PMID- 8541718
TI  - A comparison of the leakage of a monoclonal antibody from various immunoaffinity
      chromatography matrices.
AB  - Antibody leakage from immunoaffinity chromatography (IAC) matrices could reduce
      the working life of the IAC matrix and/or contaminate parenteral products,
      purified by IAC. There is therefore a need to measure the leakage of antibody
      from IAC matrices and to reduce such leakage. Using sensitive ELISAs it was found
      that the type of activated matrix, the buffer, the presence of proteases in the
      feedstock and the storage of IAC matrices between runs could all effect antibody
      leakage.

PMID- 8541719
TI  - Somatic gene therapy of human melanoma: preclinical studies and early clinical
      trials.
AB  - Several clinical trials of gene therapy of melanoma have been initiated during
      the last few years. This review examines the rationale of these studies and the
      different strategies that have been adopted to translate the preclinical results
      into clinical protocols. Animal studies with mouse melanomas are briefly reviewed
      to assess the therapeutic potential of different strategies of gene therapy. It
      has been shown that cytokine gene-modified mouse melanoma cells may induce an
      immune response resulting in tumour growth delay or even cure of tumour-bearing
      animals. In addition, normal cells modified to release cytokines and admixed with
      autologous tumour cells have shown some immunotherapeutic activity. Other
      strategies appear to be at an earlier phase of investigation in melanoma. The
      advantages and disadvantages of the different approaches in clinical trials of
      gene therapy of human melanomas are also assessed. Although no conclusive
      clinical data are yet available, the large number of ongoing studies will shortly
      provide us with more results to evaluate critically the effectiveness and future
      developments of the gene therapy of human melanoma.

PMID- 8541720
TI  - Coordinated mRNA expression of c-Kit with tyrosinase and TRP-1 in melanin
      pigmentation of normal and malignant human melanocytes and transient activation
      of tyrosinase by Kit/SCF-R.
AB  - The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic
      tyrosine kinase activity. Activation of c-Kit induces cell proliferation,
      differentiation or migration among different cell types. The present study
      provides evidence that c-Kit plays an important role in the cell differentiation
      rather than in cell proliferation in pigment cells. We found that normal human
      melanocytes and a limited number of melanoma cells, e.g. WM35, WM39 and G361 cell
      lines, expressed the c-Kit gene together with tyrosinase and TRP-1 genes. When
      exposed to alpha-melanocyte stimulating hormone, these three cell lines also
      showed an increased tyrosinase (dopa-oxidase) activity. By incubating these cells
      with 20 ng/ml of stem cell factor (SCF) which is a ligand of c-Kit receptor, we
      found a transient increase of tyrosinase activity 2-4 h post-incubation,
      indicating an early response of tyrosinase activation, either by elevating
      tyrosinase protein expression or by tyrosinase protein modification (e.g.
      phosphorylation). However, Western blot analysis using anti-tyrosinase antibody
      suggested that there was no change of tyrosinase protein expression between SCF
      treated and non-treated cells. We therefore suggest that protein modulation of
      tyrosinase (e.g. phosphorylation) plays an important role in c-Kit-induced
      melanogenesis.

PMID- 8541721
TI  - Correlation of melanoma cell motility and invasion in vitro.
AB  - Cell motility and the ability to grow invasively are crucial properties within
      the metastatic cascade. The relation of cell motility in vitro and metastatic
      behaviour of tumour cells in animal experiments indicates that they are directly
      correlated. We undertook this study to see whether a quantitative correlation
      could be found in complex in vitro systems. Using the assay of directional
      migration and a newly developed image analysis system to measure cell motility of
      K1735-M2 mouse melanoma cells and the embryonic chick heart assay of Mareel to
      follow invasion, we examined the influence of eight compounds on cell motility
      seven compounds on invasion. For stationary motility we calculated the change of
      density, area of change, area of ruffling sites (representing only changes at the
      leading edge and tail of the cell), number of ruffling sites, area of changing
      intracellular particles and number of intracellular particles. Velocity of single
      tumour cells and directional migration were also measured. In the invasion assay
      the parameters STRCSTR and INVASLOG, expressing different forms of stromal (i.e.
      embryonic chick heart) disintegration and degradation, were calculated.
      Directional migration and all parameters of stationary motility except number of
      ruffling sites, changing intracellular particles and number of changing
      intracellular particles correlated significantly (p < 0.05) with STRCSTR and
      INVASLOG. For velocity, area of change and area of ruffling we found the most
      significant correlation with parameters of invasion indicating that both
      stationary and translocative motility contribute to invasion. Our systems also
      showed that the compounds tested exerted differential effects on various aspects
      of motility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541722
TI  - Heat-mediated selective delivery of liposome-associated melphalan in murine
      melanoma.
AB  - Malignant melanoma is notable for its resistance to chemotherapy, and
      multimodality approaches are being investigated to improve therapeutic efficacy.
      Melphalan and dacarbazine are commonly used for treatment of melanoma and their
      effect is potentiated by hyperthermia. The present study attempts to enhance the
      antitumour effect of melphalan by encapsulating it in temperature-sensitive
      liposomes and using it in combination with localized hyperthermic treatment of
      tumours for targeted delivery. Small unilamellar vesicles made of synthetic
      lipids (distearoyl phosphatidyl choline and dipalmitoyl phosphatidyl choline),
      showing gel to liquid crystalline phase transition at 42 degrees C, were used for
      encapsulation of melphalan. In vivo antitumour efficacy of the combination of
      liposomal melphalan and hyperthermia was determined using B16F10 murine melanoma
      transplanted into C57Bl/6 mice. A significant reduction in tumour volume and
      increased survival time was observed in tumour-bearing mice treated with a
      combination of hyperthermia and thermosensitive liposome-encapsulated melphalan
      compared with animals treated with an equivalent dose of free melphalan with or
      without hyperthermia. These results suggest that hyperthermia in combination with
      temperature-sensitive liposome-encapsulated melphalan may serve as a useful
      targeted drug delivery system for more effective management of melanoma.

PMID- 8541723
TI  - Studies on the expression and immunogenicity of the B50 melanoma antigen and its
      relationship with calreticulin.
AB  - B50 is a 50 kDa protein antigen originally identified and isolated from cultured
      B16 murine melanoma cells; it is found in close association with a melanoma
      specific antigen termed B700. Using a specific rabbit antiserum, B50 (or B50
      cross-reactive molecules) has been shown to be expressed by 35 out of 36 cell
      lines, including melanomas, sarcomas, fibrosarcomas, carcinomas, gliomas,
      immortalized and primary fibroblasts, melanocyte and keratinocyte cell lines
      obtained from murine, human, hamster, swine, and canine donors. B50 expression is
      localized on the cellular membrane and in the cytoplasm in varying amounts in
      seven of the nine cell lines tested. Mice immunized to B50 demonstrated a
      significant tumour rejection response when subsequently challenged with B16 F10
      melanoma cells. Previous studies had indicated that B50 has significant N
      terminal amino acid sequence homology with calreticulin. Calreticulin, a calcium
      binding protein, is part of the Ro/SS-A complex. This complex is the primary
      autoantigenic determinant of the autoimmune diseases systemic lupus erythematosus
      and primary Sjogren's syndrome. We now show that sera from patients with those
      diseases contain antibodies which bind B50, although B50 itself does not bind
      calcium. Thus, B50 and calreticulin are closely related but distinct antigens.

PMID- 8541724
TI  - Anti-tyrosinase antibodies participate in the immune response to vaccination with
      anti-idiotypic antibodies mimicking the high-molecular-weight melanoma-associated
      antigen.
AB  - Seven patients with metastatic melanoma were vaccinated with anti-idiotypic
      monoclonal antibody (mAb) MK2-23 which mimics the high-molecular-weight melanoma
      associated antigen (HMW MAA). Sera samples were assayed for anti-anti-idiotypic
      antibodies, by Ab1-Ab2 complex inhibition test, for anti-B16 epitope antibodies,
      which are a heterogeneous group against various antigens presented on B16
      melanoma cells and for anti-tyrosinase antibodies, which are specific against
      tyrosinase. Our results pointed to the participation of anti-tyrosinase
      antibodies in the immune response to vaccination by anti-idiotypic antibodies
      mimicking the HMW MAA. The anti-tyrosinase antibody kinetic curves presented an
      initial increase in titres in five cases followed by decreasing titres; in two
      cases a constant decrease was noted. The inhibition assay demonstrated an
      increasing percentage of inhibition (range 17-100%) within 100-400 days of
      treatment. The titre of the anti-tyrosinase antibodies increased following the
      vaccination, then decreased--probably due to absorption of the antibodies to
      melanoma cells and normal melanocytes. A positive slope in the percentage of
      inhibition was roughly associated with a negative slope of anti-tyrosinase
      antibodies. In one case, a long-standing complete clinical response was
      accompanied by development of melanoma-associated hypopigmentation. Anti-B16
      epitope antibodies had no role in the response to vaccination. The development of
      anti-tyrosinase antibodies in response to vaccination by anti-idiotypic
      antibodies mimicking another antigen may be explained by induction of non
      specific polyclonal B lymphocytes activation, a well-recognized phenomenon in
      autoimmune disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541725
TI  - Utility of a proliferation marker in distinguishing between benign naevocellular
      naevi and naevocellular naevus-like lesions with malignant properties.
AB  - In the present study we have investigated the utility of the proliferation marker
      MIB 1 in distinguishing between benign naevocellular naevi and naevocellular
      naevus-like lesions with malignant potential. Percentages of MIB 1
      immunoreactivity in the intradermal portion of the lesions were determined. In
      benign congenital and acquired naevi, as well as in dysplastic naevi, there was
      no or only a slight intradermal melanocytic proliferation (0-2%), whereas
      vertical growth phase melanomas exhibited a substantial proliferative activity
      (11-48%). In five cases of naevus-lke lesions, which had all relapsed as
      unmistakable malignant melanomas (locally or metastatically) after primary
      surgery, there was also clear proliferative activity (9-67%). Our findings
      suggest that MIB 1 may be a useful tool in the routine histopathological
      examination of problematic naevocellular lesions.

PMID- 8541726
TI  - Serum manganese superoxide dismutase is a new tumour marker for malignant
      melanoma.
AB  - Malignant melanoma in its disseminated stage is incurable. The most widely
      accepted criteria for the prognostic evaluation of melanoma are histopathological
      and clinical parameters, and the identification of additional simple, serological
      tumour markers is thus of paramount importance. Manganese-containing superoxide
      dismutase (MnSOD) belongs to a family of metalloproteins that catalyse the
      metabolization of oxygen radicals in order to protect these cells from radical
      damage. In patients with epithelial ovarian carcinomas, serum MnSOD levels have
      been shown to be elevated in accordance with the progression of their clinical
      disease. Recently, an overexpression of MnSOD was shown to suppress the malignant
      phenotype of human malignant melanoma cells. Therefore, we determined serum MnSOD
      concentrations in 33 patients with malignant melanoma at different clinical
      stages. Whereas MnSOD serum levels in normal subjects (n = 11) and in
      dermatological patients with type I allergies (n = 10) or chronic non-allergic
      urticaria (n = 7) were below 200 ng/ml, the MnSOD serum concentrations in
      melanoma patients were statistically elevated in all clinical stages compared
      with normal (p < 0.005). These data suggest that elevated MnSOD serum
      concentrations correspond to tumour load and correlate with progression of
      malignant melanoma. Measurement of MnSOD serum levels might therefore provide a
      sensitive tool for monitoring the clinical course of melanoma.

PMID- 8541727
TI  - Photodynamic therapy: a 5-year study of its effectiveness in the treatment of
      posterior uveal melanoma, and evaluation of haematoporphyrin uptake and
      photocytotoxicity of melanoma cells in tissue culture.
AB  - A human melanoma cell line RVH-421 which selectively demonstrates melanin
      synthesis when cultured in L15 Leibowitz medium but not in RPMI medium was used
      as a model to examine haematoporphyrin derivative (HPD) uptake and the
      photocytotoxicity of photodynamic therapy (PDT). Confocal scanning microscopy and
      extraction fluorometry showed HPD uptake in both non-pigmented and pigmented
      melanoma cells. Phototoxicity was determined by incubating pigmented and non
      pigmented monolayer cells with HPD, exposing them to variable periods of white
      fluorescent light and calculating the number of viable cells in the samples
      relative to the controls. Both the non-pigmented and pigmented melanoma cells
      were affected by light-dependent cytotoxicity which was greater in the non
      pigmented cells. Melanin or other substances may reduce the photo-oxidative
      effects of PDT. Posterior uveal melanomas in 36 patients were treated with PDT
      with the longest duration of tumour control being 6.5 years. Kaplan-Meier
      survival analysis showed that 76% of melanomas were not growing at the end of the
      first year, declining to 62% at the end of the second year, with 38% showing no
      signs of growth at the end of the fifth year. No eyes were lost as a result of
      PDT. Cox's hazards analysis showed that the degree of tumour pigmentation and
      patient age at therapy significantly influence the tumour response to PDT.

PMID- 8541728
TI  - Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic
      melanoma: 5-year follow-up.
AB  - Metastatic melanoma has a grim prognosis. Response rates and survival of patients
      treated with combination chemotherapy are not superior to single-agent
      chemotherapy. This study seeks to evaluate the objective response rate and
      survival of patients with metastatic melanoma treated with multiagent
      chemotherapy, with or without tamoxifen. Forty-two patients with metastatic
      melanoma were treated from March 1982 to February 1988 with dacarbazine,
      cisplatin and carmustine, with or without tamoxifen. An overall objective
      response rate of 43% was seen (complete response rate 17%; partial response rate,
      26%). The response rate was 54% for patients treated with tamoxifen and 25% for
      patients treated without tamoxifen, but the results did not achieve statistical
      significance. Median overall survival was 412 days, and was significantly longer
      in the tamoxifen-treated group. Combination chemotherapy as described in this
      study is well-tolerated. The observation that tamoxifen appears to impact on
      survival should be interpreted with great caution due to the deficiencies in the
      design of the trial and small patient numbers. A randomized trial of this regimen
      vs single-agent chemotherapy is indicated and is currently being conducted.

PMID- 8541729
TI  - Local and systemic toxicity in 'borderline true' hyperthermic isolated perfusion
      for lower limb melanoma.
AB  - This paper reports clinical results of hyperthermal (41.5 degrees C) isolated
      perfusion of the lower limb for melanoma treatments in association with
      cytostatic drugs (L-PAM) in 10 consecutive patients. Attention is focussed on the
      toxicity effects in the search for a possible correlation between the treatment
      variables and toxicity. Careful heat administration techniques and thorough and
      accurate temperature monitoring have resulted in a uniform and closely controlled
      temperature distribution, allowing us to approach the limiting temperature value
      for possible damage both of the limb tissues and of the perfusate. Care was taken
      to avoid perfusate overheating (42 degrees C maximum). Local toxicity was
      observed between grades II and III. Systemic toxicity was of insignificant level.
      The clinical results show that high-temperature treatments with simultaneous
      administration of the cytostatic are feasible with acceptable toxicity. Further
      clinical investigations are recommended to ascertain the efficacy of the method.

PMID- 8541730
TI  - Suggestion that sunscreen use is a melanoma risk factor is based on inconclusive
      evidence.

PMID- 8541731
TI  - Bacteremia in acute pancreatitis of different etiologies.
AB  - To evaluate the rationale of using antibiotics in acute pancreatitis and to
      determine whether the indication for their use depends upon the etiology of the
      pancreatitis, the records of 202 patients with acute pancreatitis were
      retrospectively reviewed. The incidence of abnormal body temperature,
      leukocytosis, bacteremia and the results of biochemistry tests in different
      etiologies of the disease were investigated. Pancreatitis was found to be alcohol
      related (47 patients), gallstone-related (105 patients), idiopathic (26 patients)
      and miscellaneous (24 patients). On admission, 83 patients had abnormal body
      temperature and 146 patients showed leukocytosis. Bacteremia occurred in 20
      patients. Of these, 15 had gallstone-related pancreatitis, two had pancreatic
      cancers and one developed bacteremia after endoscopic retrograde cholangio
      pancreatography (ERCP). These 18 patients had abnormal biochemistry results
      (including high serum levels of direct bilirubin, alkaline phosphatase and gamma
      glutamyltransferase) and dilated bile ducts on imaging studies, indicating
      biliary infections. The remaining two patients with bacteremia included one
      alcoholic patient and one patient with idiopathic pancreatitis. The most commonly
      involved pathogens were Escherichia coli and Klebsiella pneumoniae. In addition,
      eight patients (4%) developed secondary pancreatic infections during
      hospitalization; the blood cultures of seven of these patients were negative on
      admission. Although fever and leukocytosis are not good predictors of infection
      in acute pancreatitis our results showed that bacteremia is common in patients
      whose pancreatitis is related to gallstones, ERCP or pancreatic malignancy with
      obstructive jaundice. We recommend that antibiotics be used only in this subset
      of acute pancreatitis patients.

PMID- 8541732
TI  - Analysis of K-ras gene mutations in periampullary cancers, gallbladder cancers
      and cholangiocarcinomas from paraffin-embedded tissue sections.
AB  - Point mutations of the K-ras gene were analyzed in 25 periampullary cancers (21
      ampulla vater cancers, two common bile duct cancers and two duodenal cancers),
      two gallbladder cancers and six cholangiocarcinomas. DNA extracted from the
      paraffin-embedded tissues was amplified with the polymerase chain reaction and
      subsequently analyzed by direct cycle sequencing at codons 12, 13 and 18 of the K
      ras gene. Codon 61 was first screened with single strand conformation
      polymorphism and then sequenced by direct cycle sequencing. No point mutation was
      found in any of the 25 periampullary cancers or the two gallbladder cancers.
      These results are similar to previous reports. Mutation of the K-ras gene seems
      not to play an important role in tumorigenesis of periampullary cancer. In two of
      six (33%) cholangiocarcinoma patients, point mutations were found. Both mutations
      were transitions, GGT to GAT at codon 12. The incidence of mutation was greater
      than that in Thailand (about 8%) but less than that in Japan (about 60%).
      Mutation of the K-ras gene may play varied roles in the tumorigenesis of
      cholangiocarcinoma, depending on geographic area.

PMID- 8541733
TI  - Lipoprotein responses to fish, coconut and soybean oil diets with and without
      cholesterol in the Syrian hamster.
AB  - Thirty-six young male Syrian hamsters were fed with test diets containing coconut
      oil, soybean oil or fish oil with and without 0.5% cholesterol for 6 weeks.
      Without dietary cholesterol supplementation, animals on the fish oil diet had
      significantly lower plasma total triglyceride (TG) and total cholesterol than
      those on the coconut oil or soybean oil diet. The decrease of TG was seen mainly
      in the very low density lipoprotein (VLDL) fraction. The degree of decrease in
      cholesterol was similar in all of the lipoprotein fractions. With 0.5% dietary
      cholesterol supplementation, there was no significant difference in plasma TG
      level among the three dietary groups. However, the fish oil group had
      significantly higher plasma cholesterol than the coconut oil and soybean oil
      groups. The increase of cholesterol was mainly in the VLDL and low density
      lipoprotein (LDL) fractions. In contrast to the plasma cholesterol level, the
      hepatic cholesteryl ester content was significantly lower in the cholesterol
      supplemented fish oil group than in the coconut oil and soybean oil counterparts.
      The cholesterol-supplemented fish oil group showed higher liver microsomal acyl
      coenzyme A:cholesterol acyltransferase activity than the other two groups, while
      there was no significant difference in the excretion of fecal neutral and acidic
      sterols among the three dietary groups.

PMID- 8541734
TI  - Modified Senning procedures for simple transposition of the great arteries.
AB  - From December 1990 to July 1994, 10 infants with simple transposition of the
      great arteries (TGA) underwent the Senning procedure at National Cheng Kung
      University Medical College. Their ages ranged from 1 to 8 months (mean, 4.8 +/- 2
      months), and their body weight ranged from 3.5 to 7.5 kg (mean, 5.7 +/- 1.2 kg).
      Four infants were treated with the conventional method by covering the sinoatrial
      (SA) node with the anterior right atrial flap (group 1). The other six patients
      had modified procedures, having the suture line across the caval vein, caudal to
      the SA node (group 2). Three of the group 1 patients experienced junctional
      rhythm temporarily, another had SA node dysfunction for 1 week postoperatively.
      In group 2, all patients were in sinus rhythm except one, who returned to sinus
      rhythm on the second postoperative day. There was one (10%) surgical mortality, a
      patient in group 1, and one (10%) late mortality, in group 2. The clinical follow
      up interval was 6 to 46 months (mean, 28.8 mo). All survivors were in sinus
      rhythm, and echocardiographic studies demonstrated no difference between the two
      groups as to conduit obstruction or degree of tricuspid valve regurgitation. In
      conclusion, in situations that require atrial switch for the correction of TGA, a
      suture line across the caval vein, caudal to the SA node, may be a useful
      modification to prevent arrhythmias.

PMID- 8541735
TI  - Complications of transpedicular reduction and stabilization of the thoracolumbar
      spine.
AB  - Between July 1990 and January 1994, 160 patients underwent transpedicular
      reduction and stabilization using an AO internal fixator. In this series, most of
      the patients (101 cases) had degenerative spondylolisthesis. The follow-up period
      ranged from 12 to 36 months. One hundred and thirty one patients (82%) had a good
      or excellent postoperative outcome. Sixteen (10%) had fair outcomes and 13 (8%)
      had poor outcomes. There were 26 complications (16%) secondary to this treatment.
      Improper screw placement was found in five patients, wound infection in four
      patients and dural tear with cerebrospinal fluid leakage in two patients. Two
      patients were suspected of having an iatrogenic root injury during the insertion
      of the pedicle screws. One patient with advanced spondylosis developed a
      postoperative neurologic deficit (foot drop). In the follow-up period, there was
      loss of correction of the alignment in five patients, screw breakages in three
      patients, screw pull-out in two patients and loosening of the clamps in another
      two patients. As most of the complications were preventable or treatable, pedicle
      fixation system is still highly recommended for the treatment of
      spondylolisthesis or spinal instability.

PMID- 8541736
TI  - Swyer-James syndrome associated with Noonan syndrome: report of a case.
AB  - A 28-year-old man with Noonan syndrome associated with unilateral hyperlucent
      lung is reported. He had the typical craniofacial appearance and short stature of
      Noonan syndrome; he had mild mental retardation, atrophic testis, mild funnel
      chest and kyphosis. cardiovascular abnormalities included asymmetric hypertrophic
      cardiomyopathy and a significantly different caliber of the left and right
      pulmonary arteries. The unilateral hyperlucent lung was shown to result from
      acquired nondestructive emphysema caused by nonvalvular obstruction of the
      bronchi (Swyer-James syndrome or Macleod's syndrome). To the authors' knowledge,
      this is the first reported case of Noonan syndrome associated with Swyer-James
      syndrome.

PMID- 8541737
TI  - Systemic lupus erythematosus presenting as pleural effusion: report of a case.
AB  - Systemic lupus erythematosus (SLE) presenting as a pleural effusion in a young
      male is not common. This paper describes a 20-year-old man who was admitted to
      hospital with a spiking fever, chills and cough. A chest x-ray showed alveolar
      infiltration and a moderate right-sided pleural effusion. The patient was treated
      for parapneumonic effusion. Thoracentesis was performed and cytology of the
      aspirated fluid was initially interpreted as showing only numerous
      polymorphonuclear (PMN) leukocytes. However, in spite of antibiotic treatment the
      symptoms persisted. A careful review of the cytology specimen showed classic
      lupus erythematosus (LE) cells in addition to PMN cells. Subsequent
      investigation, including antinuclear antibodies titer, confirmed the diagnosis of
      LE pleurisy. Therapy with antibiotics was discontinued and treatment with
      prednisolone 20 mg daily was begun. There was a rapid clinical response including
      resolution of the fever and pleural effusion.

PMID- 8541738
TI  - Rimmed, vacuolar distal myopathy in two Taiwanese siblings.
AB  - Distal myopathy with rimmed vacuoles (DMRV) is a rare disease that has not
      previously been reported in Taiwan. This paper reports two siblings with DMRV.
      Each showed a different pattern of disease progression, one being slowly and the
      other rapidly progressive. Both patients' initial symptoms appeared in early
      adulthood, manifesting as muscular wasting and weakness of the legs, especially
      in the distal muscles. Severe generalized involvement of skeletal muscles, with
      sparing of the facial, extraocular, bulbar, intercostal and diaphragm muscles was
      recognized in the advanced stage. The striking finding in their muscle biopsy
      specimens was the presence of "rimmed" vacuoles. Magnetic resonance imaging
      showed more severe involvement of the anterior compartment muscles of the lower
      legs. DMRV is thought to be inherited as an autosomal recessive trait and is
      distinguishable from other types of distal myopathy on the basis of clinical and
      pathologic findings. The literature on the subject is reviewed with emphasis on
      the differences between distal myopathic syndromes.

PMID- 8541739
TI  - Crossed, unfused ectopic kidney with a single ectopic ureter: report of a case.
AB  - A 10-year-old girl with an ectopic kidney and a single ectopic ureter inserted
      into the vaginal vestibule is reported. Abdominal sonography showed a hypoplastic
      left kidney located in the right lower abdomen. The associated ureter was dilated
      and tortuous, and did not open into the bladder. Diagnosis was confirmed by
      retrograde urogram via the ectopic ureteral orifice on the vestibule.

PMID- 8541740
TI  - Gas composition in Clostridium septicum gas gangrene.
AB  - Clostridial gas gangrene (myonecrosis) is a rare but catastrophic condition that
      usually occurs in patients with underlying diseases. This paper reports a fatal
      case of spontaneous clostridial gas gangrene in a 60-year-old female diabetic
      patient. The composition of gas samples from the patient's damaged muscle was
      analyzed. The results showed 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen
      and 16.1% oxygen. This gas composition supports the belief that such gas
      production occurs via glucose fermentation. This is the first time such an
      analysis has been performed in a clinical case of spontaneous clostridial gas
      gangrene.

PMID- 8541741
TI  - Clinical evaluation of ciprofloxacin ophthalmic solution in the treatment of
      refractory bacterial keratitis.
AB  - Ciprofloxacin is a fluoroquinolone antimicrobial agent inhibiting bacterial DNA
      gyrase, with good in vitro and in vivo activity against many Gram-positive and
      Gram-negative ocular pathogens. It has low toxicity, low resistance rate and low
      minimum inhibitory concentration. The purpose of this study was to evaluate the
      efficacy of ciprofloxacin in treating bacterial keratitis refractory to
      conventional therapy. Thirty patients with smear-proven bacterial ulcers were
      treated by conventional therapy. Of these, cultures were positive in 28 (93.3%)
      patients. Pseudomonas aeruginosa was isolated in 13 (46.4%) patients,
      nontuberculous mycobacteria in nine (32.1%) and other bacteria in six (21.4%).
      Fifteen patients (50%) were cured with conventional therapy. Four patients
      (13.3%) underwent surgery due to impending corneal perforation. Eleven patients
      were shifted to ciprofloxacin therapy because of poor results with conventional
      treatment. Of these, eight (72.7%) patients were treated successfully. No adverse
      events were encountered except a white crystalline precipitate in two cases which
      resolved spontaneously after discontinuation of therapy. In view of its
      effectiveness and low toxicity, ciprofloxacin should be considered in treating
      bacterial keratitis which is refractory to conventional therapy.

PMID- 8541742
TI  - Contemplating a one child world.

PMID- 8541743
TI  - Death undefeated.

PMID- 8541744
TI  - Penalties of shifting weight.

PMID- 8541745
TI  - Doctors and commitment.

PMID- 8541746
TI  - The war on drugs.

PMID- 8541747
TI  - Wine as a digestive aid: comparative antimicrobial effects of bismuth salicylate
      and red and white wine.
AB  - OBJECTIVE: To test whether red and white wines are as potent as bismuth
      salicylate against the bacteria responsible for traveller's diarrhoea to try to
      explain wine's legendary reputation as a digestive aid. DESIGN: Red and white
      wine, bismuth salicylate, two solutions containing ethanol (diluted absolute
      ethanol and tequila), and sterilised water were tested against suspensions of
      salmonella, shigella, and Escherichia coli to determine relative antibacterial
      activity. Suspensions of 10(7) colony forming units of shigella, salmonella, and
      E coli were added to the test solutions and plated on standard nutrient agar at
      0, 10, 20, 30, 60, and 120 minutes and 24 hours. Dilutions of wine and bismuth
      salicylate were then tested with E coli as the test bacterium, and the experiment
      repeated. MAIN OUTCOME MEASURES: Exposure times necessary for eradication of
      organisms for the different solutions; decreases in colony counts at the
      different exposure times for dilutions of wine and bismuth salicylates. RESULTS:
      Undiluted wine and bismuth salicylate were both effective in reducing the number
      of viable organisms (by 10(5)-10(6) colony forming units) after 20-30 minutes.
      Dilutions of wine were much more effective in decreasing colony counts than were
      similar dilutions of bismuth salicylate. CONCLUSION: The antibacterial property
      of wine is largely responsible for wine's reputation as a digestive aid.

PMID- 8541748
TI  - Cardiac chest pain: does body language help the diagnosis?

PMID- 8541749
TI  - Frostbite of the face and ears: epidemiological study of risk factors in Finnish
      conscripts.
AB  - OBJECTIVE: To determine the incidence of and the risk factors for local cold
      injuries of the face and ears in peacetime military service. DESIGN: Prospective,
      controlled epidemiological study using a questionnaire. SETTING: Finnish defence
      forces, 1976-89. SUBJECTS: 913 young male conscripts with local frostbite of the
      head that needed medical attention and 2478 uninjured control conscripts. MAIN
      OUTCOME MEASURES: Type of activity, clothing, and other risk factors at the time
      of cold injury. Odds ratios were used to calculate risk. Controls were handled as
      one group. RESULTS: The mean annual incidence of frostbite was 1.8 per 1000
      conscripts. Frostbite of the ear was most common (533 conscripts (58%)), followed
      by frostbite of the nose (197 (22%)) and of the cheeks and other regions of the
      face (183 (20%)). Most conscripts (803 (88%)) had mild or superficial frostbite.
      Risk factors included not wearing a hat with earflaps (odds ratio 18.5 for
      frostbite of the ear); not wearing a scarf (odds ratio 2.1 and 3.8 for frostbite
      of the ear and cheeks respectively); using protective ointments (odds ratio 3.3,
      4.5, and 5.6 for frostbite of the cheeks, ear, and nose respectively); being
      extremely sensitive to cold and having hands and feet that sweat profusely (odds
      ratio 3.5 for frostbite of the nose); and being transported in the open or in
      open vehicles under windy conditions (odds ratio 2.2 for frostbite of the cheek).
      CONCLUSIONS: Wearing warm clothing, including a scarf and a hat with earflaps,
      helps to prevent frostbite. Each person's sensitivity to cold may also be
      important. The routine use of protective ointments should not be recommended.

PMID- 8541750
TI  - Resting energy expenditure, substrate use, and video tapes.
AB  - OBJECTIVE: To investigate the effect of watching different types of video on
      energy expenditure. DESIGN: Randomised study assessing a "pleasant," an
      "amusing," an "exciting," and no video film clips. SUBJECTS: 12 volunteers who
      did not know the purpose of the study. MAIN OUTCOME MEASURES: Changes in energy
      expenditure, substrate use, heart rate, and aural temperature during each film
      clip. RESULTS: Energy expenditure was raised slightly (0.21 kJ/day) during the
      "exciting" film. Individual responses varied greatly. CONCLUSION: Watching
      different types of video seems to have little effect on resting metabolic rate.

PMID- 8541751
TI  - HLA-DR4 and career prospects in rheumatology: is there a link?
AB  - OBJECTIVE: To determine whether HLA type is associated with career progress in
      rheumatology. DESIGN: Comparison of HLA type after HLA analysis of samples of
      venous blood. SETTING: Department of Rheumatology Research, University of
      Birmingham. SUBJECTS: All (37) staff in the department. RESULTS: All the senior
      academics and most staff with a PhD expressed HLA-DR4. The prevalence of
      expression in each of these groups was significantly greater than that found in
      the controls. None of the junior doctors or secretaries expressed DR4.
      CONCLUSION: The junior doctors in the department have poor career prospects as
      HLA-DR4 seems to be associated with academic achievement.

PMID- 8541752
TI  - Polythenia gravis: the downside of evidence based medicine. Down End Research
      Group.

PMID- 8541753
TI  - Why do old men have big ears?

PMID- 8541754
TI  - The mark 2 human genome: a word of advice from us down here.

PMID- 8541755
TI  - The international arms trade and its impact on health.

PMID- 8541756
TI  - Infectious diseases: an ecological perspective.

PMID- 8541757
TI  - Great expectorations! The decline of public spitting: lessons for passive
      smoking?

PMID- 8541758
TI  - Hospice at home.

PMID- 8541759
TI  - The aftermath of disaster.

PMID- 8541760
TI  - How I'd like to be treated if I was terminally ill.

PMID- 8541761
TI  - A case for non-intervention.

PMID- 8541762
TI  - Postal diagnosis: breaking the bad news in the 17th century.

PMID- 8541763
TI  - A new breed of parasuicide patient.

PMID- 8541764
TI  - Florence Nightingale's fever.

PMID- 8541765
TI  - Excessive impertinence or a missed diagnosis?

PMID- 8541766
TI  - Another Christmas carol.

PMID- 8541767
TI  - White coat effects.

PMID- 8541768
TI  - Analysis of the bureaucratic unsolicited mountainous paper heap (BUMPH) that
      general practitioners received in 1994.
AB  - OBJECTIVES: To record and analyse the bureaucratic unsolicited mountainous paper
      heap (BUMPH) received by general practitioners; to make some suggestions for
      coping with the ensuing workload. DESIGN: Daily record of all BUMPH landing on
      the desk of a general practitioner in one year. SETTING: Mixed practice with one
      full time and two job sharing principals. RESULTS: 5100 pages of BUMPH arrived
      during the year. The most prolific source of origin was health authorities (1549
      pages). Fridays, Mondays, and the day after a holiday were the days BUMPH was
      most frequently seen. CONCLUSIONS: BUMPH is a major source of workload. One way
      of avoiding it is not to work on the day after a day off.

PMID- 8541769
TI  - Of no fixed abode: homeless house officers.

PMID- 8541770
TI  - Madness and care in the community: a medieval perspective.
AB  - Care in the community for insane people today is more a matter of expert
      provision than communal support. In consequence, although they are no longer
      confined to hospital, mentally ill people largely remain marginalised in a
      society that does not have the resources, nor often the inclination, to take
      responsibility for their care. The experience of insane people in medieval
      England seems to have been of a different order, as shown by a particularly well
      documented case dating from 1383. From the late 13th century congenital idiots
      were protected by law. Care of lunatics, by contrast, was primarily the
      responsibility of the family. However, where the family could not or was
      unwilling to provide, provision was made by the crown. Through the instrument of
      the inquisition, the diagnosis and social circumstances of each case were
      determined by commissioners in consultation with a local jury and all interested
      parties, including the subject himself or herself. The best interests of the
      subject remained a prime concern, and the settlement that was ordained was tried
      and enforced in law. The process was confined to those with real or personal
      estate, but it encompassed poor as well as rich and proved, through the close
      identity of the local community with the process, to be a sophisticated and
      effective mechanism for maintaining and sustaining insane people. Unlike today,
      care in the community was a communal activity that ensured a truly public
      provision for those who could not look after themselves.

PMID- 8541771
TI  - Views from the gallery.

PMID- 8541772
TI  - Gone to the devil: the murals of Ile Royale hospital.

PMID- 8541773
TI  - Early evidence of scleroderma.

PMID- 8541774
TI  - Complications of femoral nailing.

PMID- 8541775
TI  - Traumatic dislocation of the knee: a review of the literature.

PMID- 8541776
TI  - Review of outcome instruments for evaluation of anterior cruciate ligament
      reconstruction.
AB  - The need to quantify the efficacy of medical treatment has lead to the discipline
      of outcome assessment. Many instruments are available for the assessment of the
      outcome for surgical procedures in orthopaedic surgery. A review is presented of
      the general health outcome instruments used to assess the efficacy of specific
      orthopaedic procedures. To date little work has addressed the appropriate outcome
      instruments for evaluating anterior cruciate ligament reconstruction.

PMID- 8541777
TI  - The incidence of full thickness rotator cuff tears in a large cadaveric
      population.
AB  - The incidence of full thickness rotator cuff tears was determined after careful
      dissection and inspection of 235 male and female cadavers ranging in age from 27
      102 years with an average age of 64.7 years. A total of 456 shoulders were
      examined. Partial thickness tears were excluded from the study. Seventy-eight
      shoulders, 17% (53 female, 26 male) were found to have full thickness tears. The
      average age of those cadavers with tears was 77.8 years as compared to 64.7 years
      in the intact group. The incidence of full thickness tears was also found to
      increase with increasing age. In cadavers under 60 years of age the incidence of
      rotator cuff tears was 6% as opposed to 30% in those over 60 years of age.

PMID- 8541778
TI  - Paraplegia following surgical correction of scoliosis with Cotrel-Dubousset
      instrumentation.
AB  - Three patients with paraplegia following corrective surgery for idiopathic
      scoliosis, using the Cotrel-Dubousset (CD) instrumentation, were admitted to our
      department over a period of 22 months. They were operated on by three different
      surgeons and they were the first serious neurological complications in these
      surgeons' careers. The monitoring method was the "wake-up" test, applied at the
      end of the correction maneuver with the instrument. One patient presented
      paraplegia at the "wake-up" test and the other two were paraplegic shortly after
      ceasing anesthesia. Electrophysiological spinal cord monitoring during surgery
      may reduce the risks of complications.

PMID- 8541779
TI  - Subcapital fracture of a congenitally dislocated hip: revival of Girdlestone
      resection arthroplasty.
AB  - A twenty-year-old, active male with a high congenital dislocation of the hip
      sustained a displaced subcapital fracture (accompanied by a comminuted
      transarticular fracture of the ipsilateral distal femur). Such a combination of
      injuries poses a challenging problem; the English literature does not cite any
      report describing the occurrence of subcapital fractures in congenitally
      dislocated hips. This article reviews the treatment options of the fractured neck
      of the femur, and the reasons for electing to perform a Girdlestone resection
      arthroplasty.

PMID- 8541780
TI  - Osteoid osteoma of the clavicle.
AB  - We describe a case of osteoid osteoma of the clavicle in an Olympic free-style
      wrestler who presented to us with persistent and increasingly elevated pain in
      his right shoulder. Originally a persistent injury was considered to be causing
      the pain, however, the correct diagnosis was made three months after the onset of
      the symptoms. Even in sportsman where muscle pain is commonplace, non-traumatic
      conditions should be considered in the presence of persistent and increasingly
      elevated pain that is not relieved by rest and physiotherapy.

PMID- 8541781
TI  - Quasi-synchronous patellar tendon rupture.
AB  - The case of a 66-year-old male who suffered from rupture of both patellar tendons
      within a few minutes of each other is reported. The patient was not suffering
      from any underlying medical problems, and made an uneventful recovery following
      surgical repair.

PMID- 8541782
TI  - Fracture of the iliac crest following bone grafting: a case report and literature
      review.
AB  - Fracture of the anterior iliac crest following bone grafting is an extremely rare
      occurrence. Five cases have been reported in the literature, none of which were
      internally stabilized. We are reporting a sixth case. Of the six cases, our
      harvest site is the furthest posterior from the anterior superior iliac spine.
      The fracture resulted in a large displaced anterior fragment that required open
      reduction and internal fixation with plates and screws. Osteoporosis increases
      the risk of anterior iliac crest fractures following bone grafting, but
      preventive procedures can be performed.

PMID- 8541783
TI  - Intramedullary nailing after external fixation of the tibia.
AB  - Intramedullary nailing after external fixation of fractures of the tibia has high
      complication rates including nonunion and infection. The authors review the
      literature regarding this technique and refine the indications for secondary IM
      nailing. The report distinguishes between sequential secondary nailing and
      reconstructive secondary nailing. Sequential secondary nailing, as defined, is
      done by protocol and is planned from the onset of treatment. The technique
      includes only a short period in the external fixator, a planned interval between
      removal of the frame and placement of the IM nail, and specific exclusion
      criteria. This technique essentially uses the external fixator as a temporary
      traction device while the soft tissue envelope is reconstructed. Reconstructive
      procedures, as defined, are not done by protocol and not planned from the onset
      of treatment. Patients are usually in the external fixator for extended periods
      of time. The indications are variable and include delayed union, nonunion,
      malunion, and infected nonunion. The authors conclude that when done by protocol
      sequential IM nailing is safe and effective. Reconstructive IM nailing, however,
      has strict contraindications that include: a history of or an active infection of
      the pin tract, wound, or bone; the presence of an open wound or pin tract; and
      the presence of a ring or halo sequestrum. Yet reconstructive secondary
      procedures can be effective in healthy individuals if the soft tissue envelope is
      completely reestablished, if antibiotics are administered preoperatively, and the
      nail is placed without reaming.

PMID- 8541784
TI  - Spontaneous acute carpal tunnel syndrome in an anticoagulated patient.
AB  - Acute carpal tunnel syndrome secondary to intraneural hemorrhage of the median
      nerve is an unusual event. Most reports involve hemophiliacs. Only rarely has
      this disorder occurred in a patient receiving anticoagulation therapy, and in
      these cases there is usually a history of trauma. We recently treated a 42-year
      old patient receiving Coumadin medication who presented with acute carpal tunnel
      syndrome and who denied any history of trauma. Following the initial carpal
      tunnel release and drainage of hematoma, the patient was restarted on
      anticoagulation therapy and developed recurrent bleeding requiring a second
      surgical exploration. The patient eventually experienced complete recovery of
      median nerve and hand function.

PMID- 8541785
TI  - Hugh Owen Thomas: bone-setter and pioneer orthopaedist.
AB  - Hugh Owen Thomas (1834-1891) was descended from a long line of Welsh bone
      setters. He stressed the importance of rest in treatment and was responsible for
      many landmark contributions to orthopaedic surgery. He was especially celebrated
      for his design and use of splints; the famous Thomas knee splint was still in
      wide use at the end of World War II. Although he performed little open surgery,
      his logical and original principles and methods revolutionized orthopaedic
      practice. His ideas were disseminated throughout the United States by John Ridlon
      and others and there is continued interest and respect here for all facets of his
      life and teachings. He and his nephew, Robert Jones, have been called "the
      Fathers of Orthopaedic Surgery."

PMID- 8541786
TI  - [The organ culture of rabbit bladder epithelium using a perfluorocarbon
      emulsion].
AB  - The influence of perfluorocarbon emulsion on the development of the growth zone
      in the organ culture of rabbit bladder epithelium was studied. The results of
      histological investigations suggest that the preliminary treatment of epithelium
      explants with perfluorocarbon emulsion for 4 h not only preserves the explants'
      viability, but enhances the growth zone development. The treatment of explants
      with perfluorocarbon emulsion before deep freezing increases the cryoresistance
      of tissue explants and enhances development of the growth zone. The data obtained
      indicate that perfluorocarbon emulsion can be used for both the storage of tissue
      explants at +4 degrees C and their cryoconservation.

PMID- 8541787
TI  - [Markers of the metabolic changes arising as a result of ionizing radiation
      exposure].
AB  - Time-related changes have been studied in the content of extracellular DNA,
      Fe(3+)-transferrin (TF), and Cu(2+)-ceruloplasmin (CP) in the blood plasma and
      the activity of ribonucleotide reductase (RR) in the tumor cells and spleen of
      mice during the development of acute lympholeukosis P-388 and after ionizing
      irradiation. At the initial stages of leucosis P-388, the content of
      extracellular DNA increases, the TF and CP pools in the blood plasma enlarge, and
      the RR activity in the tumor cells and spleen of tumoral mice markedly increases.
      A dose-dependent increase in RR activity was also recorded in the spleen of 5-day
      old rats within 15-30 min after irradiation. The causes of these changes and the
      possibility for these indices to be used in estimating leucosis risk are
      discussed. Radiation-induced increases in RR activity are discussed in relation
      to the SOS-response to DNA damage; an increased pool of deoxyribonucleotides is
      necessary for repair of DNA. The mean contents of extracellular DNA, TF and CP in
      the blood plasma were obtained from children of different ages degrees of
      radioactive contamination suffering the consequences of the accident at the
      Chernobyl' Nuclear Power Station (n = 155). Groups of children have been isolated
      with increased, sharply decreased, and close to normal levels of extracellular
      DNA, TF, and CP. The lowered TF pool was observed in children with thyroid glands
      damaged by incorporated radioactive iodine with the degree of suppression
      determined by the dose. For most children subject to general irradiation, the TF
      and CP pools in the blood were higher than in the control, suggesting an adaptive
      response to irradiation.

PMID- 8541788
TI  - [The computer prognosis of the phenomenon of the superactivity
      neuropharmacological embryotoxic preparations by using molecular topological
      parameters and the methods of the sample recognition theory].
AB  - Discriminant functions were obtained on the basis of experimental data on the
      superactivity of synthetic analogues of the natural biogenic amines (26 active
      and 33 superactive derivatives of benzene and indole), which allow
      prognostication of the superactivity of embryotoxic compounds with respect to sea
      urchin embryos on the basis of calculated parameters of the molecules. During
      reclassification of molecules of the learning sample, the percentage of correct
      recognition is 73.1 for active, 87.9 for superactive, and 81.4% for the entire
      data bank. The prognostication capacity of the obtained functions is 73-80%.

PMID- 8541790
TI  - Benefits of exercise for type II diabetics: convergence of epidemiologic,
      physiologic, and molecular evidence.
AB  - In Canada diabetes affects approximately 5% of the population. The economic costs
      of diabetes and its attendant complications are significant, requiring
      approximately $1 billion a year from the health care system. Clearly the
      prevention and alleviation of diabetes is highly desirable. In the past few years
      there has been a remarkable convergence of physiologic, biochemical, molecular,
      and epidemiologic data, all of which indicate very strongly that exercise may be
      used as a therapeutic tool to prevent or alleviate non-insulin-dependent diabetes
      mellitus (NIDDM), or Type II diabetes. The evidence for this has been reviewed.
      Recently the significant therapeutic role of exercise for Type II diabetics has
      been endorsed by the medical community. However, there is virtually no education
      of exercise professionals in the area of diabetes and the benefits of lifestyle
      changes in treating Type II diabetics. This deficiency should be remedied. For
      the research community, the challenge now is to translate the physiologic,
      biochemical, and epidemiologic knowledge into optimally effective prescriptive
      exercise programs for Type II diabetic men and women.

PMID- 8541789
TI  - [The antimetastatic effect of low doses of lonidamine].
AB  - Antimetastatic activity of a wide range of Lonidamine doses, including low and
      ultralow doses, was studied. Low doses of the drug were shown to affect the
      frequency and intensity of metastasis formation.

PMID- 8541791
TI  - Generation of free radicals and messenger function.
AB  - Free radicals are toxic agents that are produced as by-products of metabolic
      activity. A number of antioxidant mechanisms work to protect cells from damage.
      Recent evidence indicates, however, that free radicals and related oxidants such
      as hydrogen peroxide may also have a beneficial role, working as messengers to
      control cell function. These agents are generated in response to agonists,
      production is regulated by intracellular signal pathways, and they appear to be
      used to control particular cellular processes. Free radicals may perform these
      functions in a number of cell types. Also, they are produced in muscles and there
      is evidence that they may work as messengers in smooth muscle cells.

PMID- 8541792
TI  - Effects of fatigue of rat EDL in situ on metabolism of phosphoinositides.
AB  - The study was conducted to determine the effect of persistent fatigue in situ on
      the inositol phosphate second messenger system proposed to constitute a step in
      excitation-contraction coupling. Rat EDL, after stimulation in situ for 1 hr (100
      Hz for 330 ms, 1/s), showed increased incorporation of myo-[3H]inositol into
      membrane phosphoinositides during a subsequent 4-h incubation period. The rate of
      hydrolysis of this pool resulting from 10 sec of tetanic stimulation, as well as
      the rate of production of inositol phosphates InsP, InsP2, and InsP3, were
      significantly reduced in fatigued muscles. These results suggest that the
      metabolic changes that parallel the alteration in contractile response with
      fatigue reflect a disruption in E-C coupling.

PMID- 8541793
TI  - Exercise- and cold-induced asthma.
AB  - Exercise- and cold-induced asthma are commonly recognized respiratory disorders.
      The asthmatic response includes several factors contributing to airway narrowing,
      and thus increased airway resistance. These include airway smooth muscle
      contraction, mucus accumulation, and bronchial vascular congestion as well as
      epithelial damage and vascular leakage. The etiology for these disorders is
      nonantigenic. The primary stimulus is probably a combination of airway cooling
      and drying (leading to hypertonicity of airway lining fluid). Symptoms generally
      do not occur during the stimulus period (e.g., exercise) itself. This protection
      may in part be due to increased catecholamine levels during exercise. The early
      phase response, which occurs 5 to 15 min poststimulus, may be mediated through a
      combination of (a) direct influences, (b) vagal reflexes triggered by airway
      sensory receptors, or (c) responses to mediator release. Spontaneous recovery
      occurs within 30 min to 2 hrs. There is usually a refractory period of about 1 to
      2 hrs during which responses to further stimuli are attenuated. This may be due
      to depletion of histamine and other mediators. As well, prostaglandin release
      (mediated via LTD4 which is released during exercise) inhibits further airway
      narrowing. A late phase response has been reported 4 to 10 hrs poststimulus in
      some patients. These reactions are accompanied by a second release of histamine
      and other mediators that cause inflammatory responses and epithelial damage.
      However, the exercise dependence of this response is debated.

PMID- 8541795
TI  - Our debt to Peter Stewart.

PMID- 8541794
TI  - Short-term training, muscle glycogen, and cycle endurance.
AB  - The objective of this study was to test the hypothesis that the increased
      glycogen concentration found in the working muscles following short-term training
      would result in an increase in endurance performance. Endurance performance was
      examined in 8 active but untrained males who cycled until fatigue at 65% VO2max
      prior to and following 3 consecutive days of training. Training consisted of
      cycling for 2 hrs a day at the same power output used in the prolonged fatigue
      trials. A 39% increase in cycle time, from 103 +/- 7.7 to 143 +/- 14 min (p <
      0.05), was observed following training. At fatigue prior to training, glycogen
      concentration in the vastus lateralis muscle was depleted by 75% (317 +/- 17 to
      78.8 +/- 32 mmol.glucosyl units .kg-1 d.w). Following training, glycogen
      concentration at a comparable work time was 2.3 times higher. The elevated
      glycogen level following training was due both to higher glycogen at rest and
      during exercise. The energy cost of the activity as measured by the VO2 at
      selected intervals was unchanged with training. No change (p > 0.05) in exercise
      time was observed in a control group who were subjected to similar exercise
      protocols approximately 1 to 2 weeks apart. It is concluded that short-term
      training at least in untrained individuals (VO2max averaging 43.6 +/- 2.9 ml.kg
      1.min-1) substantially elevates submaximal exercise tolerance and that the
      increase in resistance to fatigue is related to the elevated availability of
      glycogen.

PMID- 8541796
TI  - A quantitative approach to acid-base chemistry.

PMID- 8541797
TI  - Acid-base balance: origin of plasma [H+] during exercise.
AB  - According to physicochemical principles, the plasma concentration of hydrogen
      ions ([H+]), bicarbonate ([HCO3-]), and other acid-base-dependent variables are
      determined by the plasma PCO2; the strong ion difference ([SID+] = sigma [strong
      cations] - sigma [strong anions]); and the concentration of weak acids ([ATOT] =
      [HA] + [A-]). The physicochemical interactions between the acid-base-independent
      and dependent variables must recognize the constraints imposed by the law of
      electrical neutrality, dissociation equilibrium of weak acids and water, and the
      conservation of mass. This review demonstrates the usefulness of the
      physicochemical approach in studying plasma acid-base control during progressive
      exercise to exhaustion where the work rate was increased as either a slow (8
      W/min) or fast (65 W/min) ramp function. The factors contributing to changes in
      the concentration of the acid-base-independent variables, and the contribution of
      the acid-base-independent variables to the plasma [H+] and [HCO3-] during
      exercise will be discussed.

PMID- 8541798
TI  - Origins of [H+] changes in exercising skeletal muscle.
AB  - This brief review describes the main physicochemical factors that contribute to
      increases in intracellular hydrogen ion concentration ([H+]i) in mammalian
      skeletal muscle during high intensity exercise. High intensity exercise results
      in changes in the three main independent physicochemical variables: PCO2, the
      strong ion difference ([SID]), and total concentration of weak acids and bases
      ([Atot]), within the intracellular fluid compartment of contracting muscle that
      result in increased [H+]i. The decrease in [SID] contributes 62% to the increase
      in [H+]i, due to decreased [K+]i and increased [lactate]i; the decrease in
      phosphocreatine ([PCr2-]i) exerts an alkalinizing effect. The increase in [Atot],
      resulting primarily from increases in inorganic phosphate and creatine as a
      result of PCr2- breakdown, contributes 19% to the increase in [H+]i. An increase
      in the apparent proton dissociation constant (KA) for [Atot] contributes 7% to
      the increase in [H+]i. PCO2 is a relatively poor effector of changes in [H+]i,
      such that a 50-mmHg increase in PCO2 contributes only 12% to the increase in
      [H+]i during high intensity exercise.

PMID- 8541799
TI  - Extreme derangements of acid-base balance in exercise: advantages and limitations
      of the Stewart analysis.
AB  - The acid-base analysis method described by Stewart (1981) was applied to the
      greyhound, an animal that undergoes large changes in intra- and extracellular
      hydrogen ion concentrations during a race. Increases in plasma [H+] especially
      during the first 15 min of recovery, induced by increases in lactate
      concentration in the plasma, were reduced by lowering of PCO2 (hyperventilation)
      and removal of Cl- from the plasma. [H+] calculated by the Stewart method is
      similar to that measured directly with a pH electrode when the strong ion
      difference is within 10 meq/L of resting values (approximately 40 meq/L); thus
      the measured independent variables were sufficient to account for the [H+] using
      the Stewart analysis. When the strong ion difference became lower than 30 meq/L,
      increased variability between measured and calculated [H+] occurred. An error
      analysis demonstrated the importance of minimizing measurement error of all
      independent variables, including as many strong and weak electrolytes as possible
      in the analyses, using the most accurate dissociation constants possible, and
      understanding the dissociation behavior of the weak electrolytes, especially the
      plasma proteins, when using the Stewart analysis. The Stewart method of analyzing
      acid-base balance can contribute to improved training methods for obtaining
      maximum exercise performance.

PMID- 8541800
TI  - Contribution of acid-base changes to control of breathing during exercise.
AB  - The mechanisms mediating the exercise hyperpnea remain controversial; there is no
      unequivocal evidence that any of numerous proposed mechanisms mediates the
      hyperpnea. However, a great deal has been learned including the potential role of
      changes in PCO2, [H+], strong ion differences (SID), weak acids, or any other
      acid-base component. The contribution of acid-base changes to the hyperpnea
      during exercise is likely through known or postulated chemoreceptors. Two of
      these, pulmonary and intracranial chemoreceptors, do not appear critical for the
      ventilatory adjustments to meet the metabolic demands of exercise. A third, the
      carotid chemoreceptors, appear to fine-tune alveolar ventilation during exercise
      to minimize disruptions in arterial blood gases. The role of the fourth
      chemoreceptors, those within skeletal muscles, is least clear. However, there is
      evidence that they do contribute to the hyperpnea, and it is quite clear that a
      muscle chemoreflex contributes to the exercise muscle pressor reflex; thus the
      contribution of these chemoreceptors to the exercise hyperpnea requires
      additional study.

PMID- 8541801
TI  - A national consensus on guidelines for establishment of a post-exposure
      notification protocol for emergency responders. Laboratory Centre for Disease
      Control, Health Protection Branch, Health Canada.

PMID- 8541802
TI  - Iron supplying systems of Salmonella in diagnostics, epidemiology and infection.
AB  - Well-known and newly characterised mechanisms, both endogenous and exogenous, for
      the uptake of iron by Salmonella are outlined, and their possible roles at
      various stages in infection are discussed. The contributions of a detailed
      understanding of iron supplying systems to techniques for diagnosis, epidemiology
      and disease management are described.

PMID- 8541804
TI  - Concentration and avidity of anti-tetanus antibodies in mother-infant pairs:
      relation to immunization time.
AB  - The concentration and avidity of anti-tetanus antibodies in two groups of mother
      infant pairs were compared. Mothers immunized during pregnancy and their newborns
      (group A) had significantly higher antibody concentrations than mothers immunized
      at least a year before their last pregnancy and their newborns (group B) as
      measured by an indirect enzyme immunoassay (EIA) procedure. Antibody avidity of
      samples was measured by an inhibition EIA technique and urea denaturation test.
      Although antibody avidity was higher in group B, the differences were not
      significant. These findings may represent a secondary antibody response to a
      protein antigen, when considering that all mothers in both groups had received a
      primary tetanus vaccination during childhood. In mothers with a history of
      primary tetanus immunization, a single booster dose of tetanus toxoid during
      pregnancy is enough to induce protective levels of antibodies with reasonably
      high avidity in both mother and newborn.

PMID- 8541803
TI  - Structural and functional homology between periplasmic bacterial molecular
      chaperones and small heat shock proteins.
AB  - The periplasmic Yersinia pestis molecular chaperone Caf1M belongs to a
      superfamily of bacterial proteins for one of which (PapD protein of Escherichia
      coli) the immunoglobulin-like fold was solved by X-ray analysis. The N-terminal
      domain of Caf1M was found to share a 20% amino acid sequence identity with an
      inclusion body-associated protein IbpB of Escherichia coli. One of the regions
      that was compared, was 32 amino acids long, and displayed more than 40% identity,
      probability of random coincidence was 1.2 x 10(-4). IbpB is involved in a
      superfamily of small heat shock proteins which fulfil the function of molecular
      chaperone. On the basis of the revealed homology, an immunoglobulin-like one
      domain model of IbpB three-dimensional structure was designed which could be a
      prototype conformation of sHsp's. The structure suggested is in good agreement
      with the known experimental data obtained for different members of sHsp's
      superfamily.

PMID- 8541805
TI  - Effect of Brucella abortus transfer factor in preventing murine brucellosis.
AB  - Mice vaccinated with a protein extract of attenuated Brucella abortus strain 19
      had increased resistance to infection with virulent B. abortus strain 2308 and
      had increased antibody responses to strain 2308. However, resistance to infection
      and antibody responses were not increased when nonvaccinated recipient mice were
      given transfer factor preparations that were obtained from either vaccinated
      donor mice or strain 2308-infected donor mice. Vaccination of mice with the
      strain 19 extract plus treatment with each transfer factor preparation also did
      not further increase resistance to infection or antibody responses when compared
      with mice that received the vaccine alone. These results suggest that transfer
      factor from mice that have either vaccine-induced protective immunity to B.
      abortus or active B. abortus infections does not enhance antibody responses and
      resistance to infection with B. abortus.

PMID- 8541806
TI  - Incidence and pathophysiological relevance of postoperative endotoxemia.
AB  - Patients who underwent surgical procedures usually develop elevated body
      temperature, changes of plasma levels of some proteins, and leucocytosis. These
      alterations are summarized as the postoperative acute-phase reaction. Also
      endotoxin can induce the described phenomena suggesting that endotoxin may play a
      role concerning the induction of the acute phase reaction. In order to test that
      hypothesis we determined endotoxin plasma levels preoperatively and daily
      postoperatively in patients who were operated on because of goiter (n = 20),
      colonic, pancreatic and gastric diseases (n = 58). A significant increase of
      endotoxin plasma levels was found at the first and third day after abdominal
      surgery whereas after goiter surgery the increase revealed to be only very
      slight. However, the decrease between the first and second postoperative day in
      the latter group was again statistically significant suggesting postoperative
      endotoxemia even after minor operations. Furthermore a correlation between the
      amount of circulating endotoxin and pulmonary or infectious complications could
      be established in patients after major operations even at the first postoperative
      day suggesting a pathogenetic relevance of postoperative endotoxemia.

PMID- 8541808
TI  - Regulation of lipopolysaccharide-induced tumor necrosis factor production by
      cyclosporin A in mice primed with muramyl dipeptide.
AB  - The effect of cyclosporin A (CsA) on tumor necrosis factor (TNF) or interleukin-6
      (IL-6) production was evaluated in vivo in primed or unprimed mice challenged
      with lipopolysaccharide (LPS). Both pretreatment with BCG infection or with
      muramyl dipeptide (MDP) prior to LPS challenge resulted in an increase in the
      cytokine bioactivity level in the blood. CsA administration inhibited the TNF
      production. In unprimed mice, either normal or sensitized to LPS lethality by
      galactosamine treatment, a marked decrease in the cytokine level was observed
      after injection of CsA. After adrenalectomy, the yield of both TNF and IL-6
      following LPS injection was markedly elevated but decreased by CsA
      administration. Ex vivo experiments have shown that the inhibitory effect of CsA
      could be demonstrated at the level of macrophages from mice previously given the
      drug. If mice had received MDP, in vitro responses of cells to LPS were enhanced
      but again CsA decreased the mRNA expression and protein secretion.

PMID- 8541807
TI  - DNA methylation in mycobacteria: absence of methylation at GATC (Dam) and CCA/TGG
      (Dcm) sequences.
AB  - The presence of 6-methyladenine and 5-methylcytosine at Dam (GATC) and Dcm
      (CCA/TGG) sites in DNA of mycobacterial species was investigated using
      isoschizomer restriction enzymes. In all species examined, Dam and Dcm
      recognition sequences were not methylated indicating the absence of these
      methyltransferases. On the other hand, high performance liquid chromatographic
      analysis of genomic DNA from Mycobacterium smegmatis and Mycobacterium
      tuberculosis showed significant levels of 6-methyladenine and 5-methylcytosine
      suggesting the presence of DNA methyltransferases other than Dam and Dcm.
      Occurrence of methylation was also established by a sensitive genetic assay.

PMID- 8541809
TI  - Biomaterial-associated staphylococcal peritoneal infections in a neutropaenic
      mouse model.
AB  - Adhesion of staphylococcal cells to polyethylene with end point-attached heparin
      was quantified by bioluminescence. Staphylococcus epidermidis 3380 and the slime
      producing S. epidermidis RP12 adhered to the highest extent, and S. lugdunensis
      2342 to the least extent. Preincubation of the polymer with dialysis fluid
      reduced adhesion of S. epidermidis 3380 and RP12 but enhanced that of S. aureus,
      and preadsorption of the surface with fibronectin decreased subsequent adhesion
      of S. epidermidis and S. haemolyticus strains. When staphylococci were grown in
      the presence of a biomaterial their ability to activate peritoneal cells was
      decreased. The bactericidal activity was impaired, whereas ingestion of opsonized
      coagulase-negative staphylococci (CNS) strains was unaffected. With S.
      epidermidis RP12 the presence of biomaterial did not influence either
      phagocytosis or bactericidal effect of peritoneal cells. After intra-peritoneal
      challenge with staphylococcal strains, the organ uptake of S. aureus Cowan 1 was
      increased in normal mice whereas immunosuppressed mice died. CNS strains
      increased mainly in the peritoneal cavity of immunosuppressed mice. The uptake of
      bacteria in liver and kidneys was increased with S. epidermidis 3380, S.
      lugdunensis 2343 and S. schleiferi 667-88. Generally, CNS strains persisted in
      the peritoneal cavity of both normal and immunosuppressed mice. These data
      indicate that host defense mechanisms, mainly polymorphonuclear neutrophils, fail
      to eliminate CNS infections in the peritoneum, and that initial adhesion to an
      implanted biomaterial may be of lesser importance in the peritoneal cavity than
      in e.g. catheter-associated infections. There are strain-specific virulence
      factors of bacteria, and slime producing strains evade the host defense
      mechanisms more efficiently than non-slime producing strains.

PMID- 8541810
TI  - A monoclonal antibody against T-cell receptor alpha beta induces endogenous
      cytokines and prevents mice from a lethal infection with Listeria monocytogenes.
AB  - In vivo induction of cytokines by a monoclonal antibody (mAb) against T-cell
      receptor (TCR) alpha beta and the protective effect induced by the mAb on a
      lethal infection with Listeria monocytogenes were studied. Injection of anti-TCR
      alpha beta mAb induced rapid production of endogenous tumour necrosis factor in
      the spleens, and gamma interferon and interleukin-6 in the blood streams and
      spleens of mice. Administration of anti-CD4 mAb, anti-CD8 mAb, or anti-Thy1.2 mAb
      resulted in suppression of anti-TCR alpha beta mAb-induced endogenous cytokine
      production. Mice were protected against lethal L. monocytogenes infection when
      treated with anti-TCR alpha beta mAb. The protective effect was not demonstrated
      in CD4+ cell- or CD8+ cell-depleted mice. These results suggest that anti-TCR
      alpha beta mAb shows a protective effect on a lethal infection with L.
      monocytogenes in mice and that the mAb-induced endogenous cytokines might be
      involved in the effect of anti-TCR alpha beta mAb.

PMID- 8541811
TI  - Secretory monoclonal IgA class-switch variants against bacterial enteric
      pathogens in bile and intestinal secretions.
AB  - In a previous study we analyzed the molecular forms of monoclonal IgA class
      switch variants (moIgA variants) and their transport into murine respiratory
      secretions. The aim of the present study is to characterize the transport of
      moIgA variants into bile and intestinal secretions so that their applicability in
      a passive immunization model of the gut can be evaluated. Different moIgA
      variants were directly isolated from IgG1 and IgG2a producing hybridoma clones
      specific for the same surface determinants of bacterial enteric pathogens
      (Salmonella typhimurium and Campylobacter jejuni) as their respective parent IgG
      clones. Hepatobiliary transport experiments clearly revealed the selective
      transport of biologically active polymeric forms of the IgA variants into the
      murine and rat bile after intravenous injection. Biotinylation of polymeric IgA
      variants prior to intravenous injection resulted in the recovery of functional,
      labeled SIgA. Moreover biotin-labeled polymeric IgA variant was recovered in bile
      with an increased molecular weight, suggesting that the secretory component had
      been added during passage through the liver. When IgA variant and IgG parent
      clones were both used in a murine backpack tumor model for passive immunization,
      IgA variant was selectively transported into intestinal secretions in comparison
      to IgG. The experimental model described here is suitable for use in comparative
      studies on the role of IgA and IgG with identical specificity in invasive
      infections of the intestinal tract.

PMID- 8541812
TI  - Empowerment of patients: a threat or a help?

PMID- 8541813
TI  - Obstructive sleep apnoea and cardiovascular death: cause-effect?

PMID- 8541814
TI  - Frequency of obstructive sleep apnoea syndrome detected by means of a
      questionnaire in patients with coronary heart disease.
AB  - As previous studies have suggested an association between obstructive sleep apnea
      syndrome (OSA) and ischaemic heart disease, the aim of the present study was to
      evaluate the frequency of clinically relevant OSA in this selected population.
      From September 1992 to April 1993, 136 patients referred to the Cardiology Unit
      for suspected angina pectoris were asked to participate in the study. The main
      inclusion criterion was a stable coronary heart disease, diagnosed by
      angiography. A sleep questionnaire was administered by a trained physician.
      Patients who experienced one of the following symptoms: association of body mass
      index (-weight/height2) above 27.5 and heavy snoring, breathing stops, or daytime
      hypersomnolence, were selected for a nocturnal oxygen saturation recording. The
      occurrence of at least one desaturation, defined as a 4% fall from baseline, led
      to a full night-time polysomnography. One hundred and eight patients (78 males),
      satisfied the entry criteria. A pulse oximetry was performed in 15, and three
      patients experienced a significant desaturation. Finally, one patient satisfied
      the criteria of OSA. The estimated proportion of OSA amounted to 0.92%, in
      accordance with the prevalence of OSA described in the general population.
      Clinically relevant OSA does not appear to be more frequent in patients suffering
      from stable coronary heart disease. Systematic sleep investigations in such
      patients do not appear to be useful in daily clinical practice.

PMID- 8541815
TI  - Intraluminal inflammation in the airways of patients with chronic bronchitis
      after treatment with Ambroxol.
AB  - Ambroxol is a mucus-modifying drug with a known ability to stimulate surfactant
      secretion and inhibit, in vitro, the production of proinflammatory cytokines,
      neutrophil chemotaxis, and Na+ absorption by the airway epithelium. In dogs
      inhaling ozone, bronchial hyperreactivity can be inhibited by aerosolized
      Ambroxol. To verify the possibility of producing anti-inflammatory effects in a
      clinically relevant condition, 20 patients with chronic bronchitis, randomly
      divided into two balanced matched groups, were submitted to a 14 day trial with
      Ambroxol, 150 mg.day-1, or placebo, according to a double-blind design. A
      bronchoalveolar lavage (BAL) was performed the day before starting treatment (T0)
      and at the 14th day (T14). The analysis of the cellular and soluble (total
      proteins, albumin, immunoglobulin G and A (IgG and IgA)) BAL components
      demonstrated no clear modifications. In particular, neutrophil values from the
      bronchial aliquot showed a large dispersion, with no significant differences
      (Ambroxol: T0 = 13.7 +/- 5.2%, T14 = 14.0 +/- 6.8%; placebo: T0 = 3.6 +/- 1.1%,
      T14 = 5.5 +/- 2.2%). We found a nonsignificant increase of phospholipids in BAL
      supernatants from Ambroxol-treated patients (2.5 +/- 1.9 vs 3.0 +/- 1.9
      micrograms.mg-1 of protein); whilst in the placebo group data before and after
      treatment were superimposable (2.2 +/- 1.5 vs 2.3 +/- 1.9 micrograms.mg-1 of
      protein). In conclusion, we have failed to demonstrate that conventional
      treatment with oral Ambroxol can modify surfactant and BAL cell populations in
      the airways of patients with chronic bronchitis.

PMID- 8541816
TI  - Prevalence and repeatability of the cough response induced by inhalation of low
      chloride ion solutions in normal subjects.
AB  - Although the inhalation of low Cl- ion solutions has often been used to induce
      cough, the prevalence and repeatability of the challenge has never been studied
      in detail. We, therefore, examined cough response in a group of 59 volunteers
      (aged 15-57 yrs; 34 females and 25 males; 20 smokers) to ascertain prevalence and
      repeatability. Each subject performed, 2 weeks apart, two identical cough
      challenges by inhaling four isosmolar solutions with decreasing Cl- ion
      concentrations (150, 75, 37.5 and 0 mM). Each solution was delivered by a
      DeVilbiss 65 ultrasonic nebulizer (mean output: 1.9 mL.min-1) for 1 min, and the
      number of coughs was counted during the inhalation. Cough response was expressed
      as number of coughs.min-1. Significance of response to the cough challenge was
      assessed on the basis of mean number of coughs.min-1 and 95% upper confidence
      limit (CL) of response to the Cl- free solution in the whole population. Cough
      threshold for a significant response was greater than 8 coughs.min-1. Out of 59
      subjects, only 20 exceeded the cough threshold (34%) after inhaling the Cl- free
      solution. A concentration-response effect was evident only when inhaling 37.5 and
      0 mM Cl- ion solutions. A significant cough response was more likely among
      females (p = 0.03). Smoking did not significantly affect the prevalence of
      response. Coefficients of repeatability of cough response to 37.5 and 0 mM Cl-
      solutions in 20 responders were equal to 10.1 and 12.6, respectively. We conclude
      that a significant cough response to low Cl- ion solutions develops in
      approximately 1 out of 3 of challenged volunteers and that repeatability is not
      satisfactory. We suggest that cough threshold and repeatability should be
      preliminarily assessed, especially when the challenge is used to study the
      antitussive activity of drugs.

PMID- 8541817
TI  - Tracheobronchial involvement in 84 cases of pulmonary tuberculosis.
AB  - In suspected pulmonary tuberculosis (TB), tracheobronchial examination is
      required for patients with clinical and radiographic features consistent with
      tuberculosis disease but with negative sputum for Mycobacterium tuberculosis. We
      report the endoscopic findings of 84 patients who underwent fibreoptic
      bronchoscopy in recent years, and whose cultures of biological specimens grew M
      tuberculosis. Cough (86%) and fever (69%) were the most common symptoms, followed
      by sputum (67%), dyspnoea (30%) and haemoptysis (27%). Chest radiographic
      abnormalities were mostly localized (60%) with prevalence in the upper lobes; in
      two cases chest radiography was normal. Sixty two patients (74%) showed
      endoscopic abnormalities: 1) mucosal inflammation; 2) submucosal granulomas and
      polyps; and 3) stenoses. They were localized in 58% of patients and diffuse in
      42%. Five patients were checked several times during the year following the
      diagnosis because of a high degree of tracheobronchial involvement. Only one
      subject recovered, whilst in the other four stenotic sequelae were found.
      Fibreoptic bronchoscopy confirmed its usefulness in the diagnosis of tuberculosis
      and in monitoring the course and the outcome of the bronchial tuberculosis
      involvement.

PMID- 8541818
TI  - Chronic eosinophilic pneumonia in rheumatoid arthritis.
AB  - We report the case of a 47 year old woman with rheumatoid arthritis and
      infiltrates on chest radiogram. Typical features of eosinophilic pneumonia were
      detected upon open lung biopsy, probably unrelated to hydroxychloroquine, the
      only drug administered to the patient. Good response to steroids was obtained.
      This case brings to light one more example of the rare association between
      chronic eosinophilic pneumonia and rheumatoid arthritis.

PMID- 8541819
TI  - Castleman's disease presenting as an asymptomatic solitary pulmonary nodule.
AB  - We report the case of a 51 year old white woman with an asymptomatic solitary
      pulmonary nodule, fortuitously discovered on chest radiography. Her physical
      examination and biochemical tests were unremarkable for pathological findings.
      Thoracic computed tomography (CT) scan and nuclear magnetic resonance (NMR)
      spectroscopy confirmed the presence of a dishomogeneous thick lesion of lobular
      shape, localized between the middle and lower lobe of the right lung. Fibreoptic
      bronchoscopic examination failed to produce histological diagnosis of the lesion.
      Surgical removal of the lesion demonstrated intraparenchymal localization of
      Castelman's disease (giant lymph node hyperplasia). Three years after surgery, no
      sign of disease recurrence has been recorded.

PMID- 8541820
TI  - Acute bronchial infection in chronic obstructive pulmonary disease.
AB  - Bacterial bronchial infection is a frequent cause of COPD exacerbation but not
      its only aetiology. Increased purulent expectorant appears to be its best
      indicator rather than fever, non-productive cough or dyspnoea. The clinician must
      try to recognize this condition rather than systematically prescribe empirical
      antibiotics. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella
      catarrhalis are the major pathogens. Although atypical bacteria are not frequent,
      Chlamydia pneumoniae could play significant role. During the last years, new
      antibiotics, much more expensive than other regimens, are widely prescribed,
      often without a rational approach. In patients not already on antibiotics, sputum
      Gram stain is useful for deciding which patient should be treated and what would
      be the best anti-biotic. When it is not available, the chosen antibiotic must be
      at least active against three major pathogens according to the local
      susceptibility patterns. In patients not responding to the initial treatment, the
      consideration of its potential spectrum holes is then more useful than sputum
      examination.

PMID- 8541821
TI  - Role of surfactant in the pathophysiology of the acute respiratory distress
      syndrome (ARDS).
AB  - Acute respiratory distress syndrome (ARDS) has become a well-recognized condition
      that can result from a number of different causes that lead to injury of the
      alveolar-capillary membrane. This results in high-permeability pulmonary oedema
      that disturbs the pulmonary surfactant system. In ARDS, the treatments available
      are still inadequate and morbidity, mortality, and costs remain unacceptably
      high. In the last 15 yrs, the morbidity and mortality rates of premature infants
      suffering from the respiratory distress syndrome (RDS) due to surfactant
      deficiency, have been reduced by exogenous surfactant therapy, and this treatment
      is now routinely used in most neonatal intensive care units. At this moment, only
      a few case reports and results of limited clinical pilot studies are available,
      in which patients with ARDS are treated with exogenous surfactant. Although the
      results from these studies are not consistent, the best results have been seen in
      patients treated with high concentrations or multiple doses of surfactant. It has
      been suggested that the increased permeability changes, along with the
      inflammatory response, lead to accumulation of plasma components in the alveolar
      space, causing inhibition of the instilled surfactant in a dose-dependent way.
      Thus, for treatment of ARDS, a high concentration of surfactant is required to
      overcome the inhibitory effect of plasma components. However, a few questions
      remain unanswered, including: When should surfactant treatment start? Which
      dosage? Of which type of surfactant? Which method of administration should be
      used, in combination with which type of ventilatory support, etc.?

PMID- 8541822
TI  - Noninvasive ventilation in the management of decompensated COPD.
AB  - Decompensated chronic obstructive pulmonary disease (COPD) is likely to remain a
      common medical emergency for the foreseeable future. Decompensation occurs when
      the capacity of the respiratory muscle pump is less than the load placed upon it.
      Even with optimal medical therapy, the mortality rate remains high. Noninvasive
      positive pressure ventilation (NIV) is a new technique, which is increasingly
      used as an alternative to mechanical endotracheal ventilation (ETV). In this
      review we discuss the existing literature, consider unresolved areas for future
      research and describe practice in our own hospital.

PMID- 8541823
TI  - Antileucoprotease in the airways and emphysema.
AB  - Antileucoprotease (ALP) is a natural occurring anti-elastase, and is produced in
      the epithelium of the conducting airways. It is a small protein, consisting of
      107 amino-acids arranged in 2 domains. The second domain carries the
      antiproteolytic active site, the first is responsible for antimicrobial activity.
      In hamsters, intratracheal installation of ALP prevents the development of
      emphysema after administration of elastase. The daily production of ALP is
      remarkably constant, even during exacerbations of COPD. In the human lung a
      positive correlation was found between the number of ALP-producing bronchiolar
      cells and small airway's disease and emphysema. ALP is able to penetrate the
      alveolar-capillary membrane and has a tendency to associate with elastic fibers.

PMID- 8541824
TI  - Gene therapy for alpha 1-antitrypsin deficiency.
AB  - Alpha 1-antitrypsin deficiency is associated with pulmonary emphysema and liver
      cirrhosis. The pathogenesis and treatment is reviewed with particular emphasis on
      gene therapy for emphysema. The technology of gene transfer using viruses and
      liposomes is developing fast and animal experiments have confirmed the
      feasibility of gene therapy for alpha 1-antitrypsin deficiency (AATD). So far
      only subtherapeutic levels of protein have been produced but human trials are
      starting and progress can be expected.

PMID- 8541825
TI  - Smoking and health: a physician's responsibility. A statement of the Joint
      Committee on Smoking and Health. American College of Chest Physicians, American
      Thoracic Society, Asia Pacific Society of Respirology, Canadian Thoracic Society,
      European Respiratory Society, International Union Against Tuberculosis and Lung
      Disease.
AB  - Tobacco use, particularly cigarette smoking, is a major cause of preventable
      disease and premature death worldwide. Both smokers and nonsmokers exposed to
      environmental tobacco smoke are at risk. Cessation of smoking reduces risks.
      Although the addicting properties of nicotine can make cessation difficult, both
      medical interventions aimed at helping smokers quit and social policies aimed at
      control of cigarette smoking can have significant benefits. Physicians should
      play an active role in control of smoking by ensuring that counselling and
      pharmacological therapy must be available for the individual smoker. Physicians
      should also participate in the public debate regarding smoking both individually
      and through medical organizations. As smoking represents a threat to the public
      health, physicians must take a strong and active role seeking its control.

PMID- 8541826
TI  - The effects of a cognitive behavioural intervention in asthmatic patients.
AB  - There is evidence that educational programmes may improve patient's compliance
      with asthma treatment and control symptoms. Whilst medical parameters have been
      thoroughly studied, few data are available concerning psychological intervention.
      The aim of our open pilot study was to verify whether any difference in perceived
      illness and response style to asthma existed in the patients enrolled in an
      Asthma Rehabilitation Group (ARG) and in a Control Group (CG). Forty consecutive
      asthmatics were randomly enrolled, all of whom were diagnosed, treated and
      followed-up according to the International Guidelines. Both groups underwent a
      psychological assessment at baseline and after one year. A battery of
      questionnaires was used to obtain data relating to baseline characteristics
      (anxiety, depression, psychophysiological disorders), emotional reactions to
      asthma attacks (panic-fear, etc,) and cognitive variables (external control,
      psychological stigma, internal beliefs, external chance, etc.) involved in the
      perceived illness. In addition, the Asthma Rehabilitation Group patients
      underwent an educational programme and a cognitive-behavioural intervention. In
      both groups, a reduction of anxiety and depression scores was observed, as well
      as a significant improvement of the medical parameters evaluated. Only the Asthma
      Rehabilitation Group reported lower scores on the Psychophysiological
      Questionnaire and on the External Control Subscale after 1 year. The Control
      Group reported higher score on the External Chance Scale. The data of our study
      seem to confirm the effectiveness of psychological intervention on the cognitive
      skills involved in the perception and management of asthma. Larger scale studies
      on this topic are suggested.

PMID- 8541827
TI  - Mycobacterium chelonae and fibreoptic bronchoscopy.

PMID- 8541828
TI  - Something new in coping with invasive fungal infections?

PMID- 8541829
TI  - Cloning and characterization of alternatively spliced isoforms of Dp71.
AB  - Dp71, a C-terminal isoform of dystrophin, has been identified as the major DMD
      gene product in many nonmuscle tissues. In this report, reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to clone and characterize four
      alternatively spliced Dp71 transcripts from cultured human amniocytes. The cDNAs
      encoding these Dp71 transcripts were shown to be alternatively spliced for exons
      71 and/or 78. RT-PCR analysis also revealed that Dp71 transcripts alternatively
      spliced for exons 71 and/or 78 were expressed at varying levels in a number of
      adult human tissues, including muscle, heart, brain, kidney, lung, testis and
      liver. To investigate size heterogeneity at the translational level, Dp71 cDNAs
      isolated from amniocytes were expressed in E.coli to generate recombinant Dp71
      fusion proteins. These fusion proteins were identified on immunoblots using
      antibodies specific for the C-terminal sequences of dystrophin that either
      included (antibody 1461) or excluded exon 78 (antibody 462B). The molecular
      masses of the Dp71 fusion proteins ranged from 71-75 kDa on SDS-PAGE, consistent
      with their predicted values. Immunoblot analysis using antibodies 1461 and 462B
      identified multiple Dp71 isoforms of approximately 70-75 kDa on SDS-PAGE in total
      protein lysates from amniocytes and various adult human tissues. This variation
      in molecular mass is consistent with the expression of Dp71 isoforms derived from
      transcripts alternatively spliced for exons 71 and/or 78. Total protein lysates
      from normal skeletal muscle, DMD muscle, amniocytes and brain were shown to
      contain beta-dystroglycan, a component of the dystrophin-associated glycoprotein
      complex (DGC).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541830
TI  - Population genetics of trinucleotide repeat polymorphisms.
AB  - Trinucleotide repeats at five disease loci (DM, DRPLA, HD, SBMA and SCA1) were
      surveyed in phenotypically normal individuals from three continental populations.
      This is the first analysis to examine the population dynamics of these five
      disease-related trinucleotide repeats in the same individuals from worldwide
      populations. Roughly half of all alleles observed at each locus are shared
      between all continental groups. For three loci, disease prevalence in each
      population corresponds with the number of alleles in the upper tail of the allele
      size distribution. The allele-size distributions of African, Asian and Caucasian
      groups show a high degree of variation, and gene diversity estimates for
      trinucleotide repeat loci exceed estimates derived from dinucleotide or
      tetranucleotide repeats. Analyses that compared infinite alleles and stepwise
      mutation models suggest that normal variation at trinucleotide loci is not
      generated by stepwise mutation alone. Trees constructed for subpopulations using
      trinucleotide repeat loci show accurate continental clustering. Interpopulation
      genetic distance estimates show remarkable similarity to distance estimates
      produced from tetranucleotide repeats or nuclear restriction site polymorphisms.
      This finding is especially noteworthy in light of the fact that trinucleotide
      repeat polymorphisms at these loci can cause disease, while restriction site and
      tetranucleotide polymorphisms appear to be selectively neutral. In contrast,
      genetic distance estimates from trinucleotide loci are poorly correlated with
      genetic distance estimates from mitochondrial sequence data.

PMID- 8541831
TI  - Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and
      mutant enzymes in Escherichia coli.
AB  - We have cloned, sequenced, and expressed cDNAs encoding wild type human glutaryl
      CoA dehydrogenase subunit, and have expressed a mutant enzyme found in a patient
      with glutaric acidemia type I. The mutant protein is expressed at the same level
      as the wild type in Escherichia coli, but has less than 1% of the activity of
      wild-type dehydrogenase. We also present evidence that the glutaryl-CoA
      dehydrogenase transcript is alternatively spliced in human fibroblasts and liver;
      the alternatively spliced mRNA, when expressed in E.coli, encodes a stable but
      inactive protein. Purified expressed human glutaryl-CoA dehydrogenase has kinetic
      constants similar to those of the previously purified porcine dehydrogenase. The
      primary translation product from in vitro transcribed glutaryl-CoA dehydrogenase
      mRNA is translocated into mitochondria and processed in the same manner as most
      other nuclear-encoded mitochondrial proteins. Human glutaryl-CoA dehydrogenase
      shows 53% sequence similarity to porcine medium chain acyl-CoA dehydrogenase, and
      these similarities were utilized to predict structure-function relationships in
      glutaryl-CoA dehydrogenase.

PMID- 8541833
TI  - cDNA selection from 10 Mb of chromosome 21 DNA: efficiency in transcriptional
      mapping and reflections of genome organization.
AB  - The technique of cDNA hybridization selection has been applied individually to 16
      YAC clones mapping to various regions of the long arm of human chromosome 21.
      YACs represented approximately 10 Mb of non-overlapping DNA, and cDNA sources
      included fetal brain, whole fetus, and adult testes, thymus, liver and spleen.
      Sequencing, Northern analysis, RT-PCR and cDNA library screenings have been used
      to identify and partially characterize a non-redundant set of novel genes. A
      preliminary analysis strategy of the selected cDNAs has proven rapid and
      effective for isolation of the more highly represented genes and is suitable for
      survey transcriptional mapping efforts. By scaling up to screen > 1000 cDNA
      fragments per 100 kb of YAC DNA, more rare transcripts are identified and lead to
      comprehensive gene maps. Strong regional variations in transcriptional activity
      were observed, with gene densities ranging from < 1/2000 kb to > 1/15 kb. This
      effort has produced a large number of new genes of potential relevance to Down
      Syndrome.

PMID- 8541832
TI  - A novel L23-related gene 40 kb downstream of the imprinted H19 gene is
      biallelically expressed in mid-fetal and adult human tissues.
AB  - The closely linked IGF2 and H19 genes on human chromosome 11p15.5 are
      monoallelically expressed as a result of genomic imprinting and show altered
      expression in Wilms' tumors (WTs). To map regional imprinting we have sought to
      isolate additional human genes close to IGF2/H19 and to characterize their
      allelic expression patterns. Here we report a novel gene, provisionally named
      L23MRP [L23 (mitochondrial)-related protein], which is oriented 'tail-to-tail'
      with H19 and is transcribed to within 40 kb of the last H19 exon. L23MRP is
      expressed biallelically in many mid-fetal and adult human tissues. This gene is
      also expressed at normal levels in WTs which have lost expression of H19 either
      via loss of the maternal chromosome 11p15.5 or via an epigenetic pathway
      involving site-specific DNA hypermethylation. These data indicate that, at least
      in post-embryonic stages, L23MRP is functionally insulated from the IGF2/H19
      imprinted domain.

PMID- 8541834
TI  - Single sperm analysis of the trinucleotide repeats in the Huntington's disease
      gene: quantification of the mutation frequency spectrum.
AB  - The CAG triplet repeat region of the Huntington's disease gene was amplified in
      923 single sperm from three affected and two normal individuals. Average-size
      alleles (15-18 repeats) showed only three contraction mutations among 475 sperm
      (0.6%). A 30 repeat normal allele showed an 11% mutation frequency. The mutation
      frequency of a 36 repeat intermediate allele was 53% with 8% of all gametes
      having expansions which brought the allele size into the HD disease range (> or =
      38 repeats). Disease alleles (38-51 repeats) showed a very high mutation
      frequency (92-99%). As repeat number increased there was a marked elevation in
      the frequency of expansions, in the mean number of repeats added per expansion
      and the size of the largest observed expansion. Contraction frequencies also
      appeared to increase with allele size but decreased as repeat number exceeded 36.
      Our sperm typing data are of a discrete nature rather than consisting of smears
      of PCR product from pooled sperm. This allowed the observed mutation frequency
      spectra to be compared to the distribution calculated using discrete stochastic
      models based on current molecular ideas of the expansion process. An excellent
      fit was found when the model specified that a random number of repeats are added
      during the progression of the polymerase through the repeated region.

PMID- 8541835
TI  - The upstream stimulatory factor functionally interacts with the Alzheimer amyloid
      beta-protein precursor gene.
AB  - The amyloid beta-protein precursor (APP) gives rise to the A beta peptide, which
      is deposited in the brains of patients with Alzheimer's disease and Down's
      syndrome. Overexpression of APP due to a third copy of the gene appears to
      correlate with very early onset of Alzheimer's disease neuropathology in the
      brains of Down's syndrome patients. Thus, the identification of the factors
      involved with transcriptional regulation of the APP gene could provide critical
      clues regarding the events leading to the formation of amyloid deposits. An
      overlapping AP-1/AP-4 site in the proximal promoter region (-39 to -49) of the
      human APP gene has previously been shown to increase transcription 4-fold. Here
      we identify the factor binding specifically to this element as the upstream
      stimulatory factor USF, unrelated to the c-fos/c-jun complex or the AP-4 factor.
      In vitro transcription and co-transfection studies show that USF activates
      transcription from the APP promoter and that the AP-1/AP-4 element participates
      in this activation. Modulation of APP expression via regulation of USF could
      potentially ameliorate the production of Alzheimer-augmented beta-amyloid.

PMID- 8541836
TI  - Sequence microheterogeneity in apolipoprotein(a) gene repeats and the
      relationship to plasma Lp(a) levels.
AB  - Lipoprotein(a) [Lp(a)] is a cholesterol ester-rich atherogenic lipoprotein that
      is composed of a particle of low density lipoprotein and a large glycoprotein,
      apolipoprotein(a) [apo(a)]. Apolipoprotein(a) varies in size over a approximately
      500 kDa range due to inter-allelic differences in the number of tandemly repeated
      kringle 4 (K4)-encoding 5.5 kb sequences in the apo(a) gene. Only one of the 10
      different types of K4 repeats in the apo(a) gene, the so-called type 2 K4
      repeats, vary in number between apo(a) alleles. In this paper, we show that there
      is microheterogeneity within the sequence of the type 2 K4 repeat. DraIII
      restriction digestion and genomic blotting revealed that a subset of the type 2
      K4-encoding sequences contained a DraIII site (K4-D). The proportion of apo(a)
      alleles that had at least one K4-D repeat ranged from 25% in Caucasians to 50% in
      the Chinese. K4-D repeats were clustered at the end(s) of the type 2 K4 tandem
      array and the number and patterns of the K4-D repeats were in linkage
      disequilibrium with flanking sequence polymorphisms; these features are
      remarkably similar to the minisatellite variant repeats (MVRs) found in variable
      number of tandem repeat sequences (VNTRs). In addition, a DraIII pattern that
      comprised 9% of the sample was invariably associated with low plasma levels of
      Lp(a) in Caucasians.

PMID- 8541837
TI  - A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser)
      contributes to the expression of familial combined hyperlipidemia.
AB  - We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and
      their exon-intron boundaries of the LPL-gene in 169 unrelated male patients
      suffering from familial combined hyperlipidemia (FCH). Twenty patients were found
      to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis
      revealed one common mutation (Asn291Ser) in all these cases. This mutation was
      talso present in 215 male controls, albeit at a lower frequency than in FCH
      patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid,
      lipoprotein and apolipoprotein levels demonstrated an association between the
      presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/-
      0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying
      this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36
      mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/-
      1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low
      HDL-cholesterol phenotype in carriers of this substitution was most obvious when
      BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a
      common mutation in the LPL-gene that is associated with lipoprotein
      abnormalities, indicating that defective LPL is at least one of the factors
      contributing to the FCH-phenotype.

PMID- 8541838
TI  - Candidate regions for a testicular cancer susceptibility gene.
AB  - Epidemiological data suggest the presence of a susceptibility gene for testicular
      cancer in some families. Families with multiple cases of testicular cancer are
      rare and almost all those reported have only two affected members. We have
      performed a sib-pair analysis on 35 families in which there are either two or
      three affected brothers. These families have been typed for 220 autosomal
      microsatellite markers spaced 10-20 cM throughout the genome. Six regions which
      gave a LOD score of more than 1.0 on formal linkage analysis or a P value of 0.05
      or less using a non-parametric approach are considered as candidate regions for a
      susceptibility gene. Of particular interest is one region on chromosome 4. Two
      neighbouring probes in this region both scored positively with LOD score of 2.60
      on multipoint analysis. An International Testis Cancer Linkage Consortium has
      been formed to pool resources and will investigate these findings further with
      the world-wide collection of families.

PMID- 8541839
TI  - A muscle-specific DNase I-like gene in human Xq28.
AB  - A novel cDNA which maps to human Xq28 has been isolated and characterized.
      Sequence similarity to DNase I is high at the DNA and peptide sequence levels.
      The transcript is present at highest levels in skeletal and cardiac muscle, with
      lower expression in other tissues. Mutation analysis has been performed using DNA
      samples from two unrelated patients with Barth syndrome, and from 11 unrelated
      patients with Emery-Dreifuss muscular dystrophy, two genetic disorders linked to
      Xq28. No disease-associated mutations were detected in the coding region of the
      gene; however, a novel 190 base pair insertion/deletion polymorphism was found in
      the 3' untranslated region. Translation of the long open reading frame found in
      the cDNA yields a putative 302 amino acid protein with 37.6% identity to human
      DNase I. The protein is predicted to contain a signal sequence at the amino
      terminus, a transmembrane domain near the carboxyl terminus, and a helix-loop
      helix domain.

PMID- 8541840
TI  - Proximal deletions of the long arm of the Y chromosome suggest a critical region
      associated with a specific subset of characteristic Turner stigmata.
AB  - Turner syndrome is a complex human disorder that generally associates a 45,X
      karyotype to a female phenotype presenting with gonadal dysgenesis, short stature
      and a number of characteristic somatic features. It has been hypothesized that
      this specific phenotype was the consequence of the haploinsufficiency of some X
      linked genes having functional homologs on the Y chromosome. Here we describe
      four patients with deletions of the long arm of their Y chromosome and presenting
      with azoospermia and with or without Turner stigmata. Analysis of their
      breakpoints by Southern blotting and Y-specific sequence tagged sites (STS)
      allows us to delimit a region located in proximal interval 5 of the Y chromosome
      involved in skeletal development and growth.

PMID- 8541841
TI  - p16 (CDKN2) is a major deletion target at 9p21 in bladder cancer.
AB  - The p16 gene has been identified as a candidate tumour suppressor gene at 9p21, a
      region commonly deleted in bladder cancer. We screened 140 bladder tumours and 16
      cell lines for deletions and sequence variants of p16. Eight cell lines showed
      homozygous deletion of p16 and two had small sequence variations. All 13 tumours
      with small defined deletions of 9p21, 18/31 (58%) of tumours with monosomy 9 and
      9/91 (10%) of tumours with no chromosome 9 loss of heterozygosity had homozygous
      deletion of p16. No tumour-specific sequence variants were identified. Deletion
      mapping revealed a nested set of deletions focused on p16. Six deletions involved
      p16 but not the related and adjacent gene p15 and one tumour had an intragenic
      deletion of p16. All other deletions involved both p16 and p15. We conclude that
      p16 represents the major target for deletion at 9p21 in bladder cancer.

PMID- 8541842
TI  - Pretibial epidermolysis bullosa: genetic linkage to COL7A1 and identification of
      a glycine-to-cysteine substitution in the triple-helical domain of type VII
      collagen.
AB  - Pretibial epidermolysis bullosa (PEB) is a rare variant of dominant dystrophic EB
      (DDEB) in which recurrent blistering with scarring predominantly involves the
      pretibial skin. Although blistering appears to be localized clinically, electron
      microscopy of the dermalepidermal junction in patients with PEB reveals anchoring
      fibril abnormalities that are not restricted to the predilection sites.
      Furthermore, PEB cannot be distinguished from the generalized (Cockayne-Touraine
      and Pasini) types of DDEB on the basis of anchoring fibril morphology alone. The
      generalized forms of DDEB have been linked to the type VII collagen gene (COL7A1)
      on chromosome 3p21. In this study, we sought to test the hypothesis that
      mutations underlying PEB also reside in COL7A1. We initiated mutational analysis
      in COL7A1 in a large five-generation PEB family of Taiwanese descent. We
      identified a G-to-T transversion at nt position 7867, which results in a glycine
      to-cysteine substitution (G2623C) in exon 105. This mutation was confirmed in
      affected family members using the loss of a SmaI restriction site, and when used
      for linkage analysis, together with an intragenic PvuII polymorphism and several
      flanking markers, resulted in a LOD score of Z = 3.61 at theta = 0 in this
      family. This is the first demonstration of genetic linkage and mutation analysis
      in PEB, and illustrates that the Cockayne-Touraine, Pasini, and now the pretibial
      clinical variants of DDEB are allelic, resulting from different glycine
      substitution mutations in the type VII collagen gene.

PMID- 8541843
TI  - Sequence variation and size ranges of CAG repeats in the Machado-Joseph disease,
      spinocerebellar ataxia type 1 and androgen receptor genes.
AB  - A subgroup of trinucleotide repeat diseases result from abnormal expansions of
      CAG repeats which are translated into polyglutamine stretches. As yet there is
      little understanding of how the polyglutamines function either normally, or when
      expanded. We have investigated these sequences in the Machado-Joseph disease,
      androgen receptor and spinocerebellar ataxia type 1 genes in humans and other
      primates. None of the 748 normal chromosomes that were examined had more than 34
      uninterrupted glutamine codons in the Machado-Joseph disease gene. Similarly, no
      normal alleles with more than 39 uninterrupted glutamine codons have been
      reported for the other disease genes associated with polyglutamine expansions.
      Sequence analyses of the repeats in primates revealed shorter polyglutamine
      stretches in some of the non-human primates at all three loci and marked
      diversions from the expected polyglutamines in the orang-utan Machado-Joseph gene
      and in the marmoset spinocerebellar ataxia type 1 gene. These data suggest that
      conservation of these polyglutamine stretches may not always be necessary for
      normal gene function.

PMID- 8541844
TI  - The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial
      biogenesis, is alternatively spliced in human tissues and cell lines.
AB  - Nuclear respiratory factor 1 (nrf-1) is a transcriptional activator that is most
      probably essential in the regulation of mitochondrial biogenesis. In studies of
      the expression of the NRF-1 gene in cultured human fibroblasts, using RT-PCR, we
      identified two distinct transcripts, one of which contained an in-frame deletion
      of 198 bp. Analysis of genomic DNA by sequencing, showed that the shorter mRNA is
      the result of alternative splicing (exon skipping). The shorter transcript will
      result in an isoform of the protein that lacks the carboxy-terminal part of the
      DNA binding domain, which might influence transcriptional activation by normal
      nrf-1. The alternatively spliced transcript was also present in other human cell
      lines and in several human tissues. A quantitative PCR analysis showed that the
      percentages of the alternatively spliced transcript ranged from 3 to 17%.
      Differences in the percentage of alternatively spliced NRF-1 pre-mRNA may
      influence mitochondrial biogenesis under variable physiological conditions and
      could play a role in distinct mitochondrial diseases.

PMID- 8541845
TI  - The introduction of two silent mutations into a CFTR cDNA construct allows
      improved detection of exogenous mRNA in gene transfer experiments.
AB  - Phase one clinical trials for gene therapy of cystic fibrosis are in progress
      using either liposomes or adenoviral vectors for CFTR gene transfer to epithelial
      cells in the airways. In addition to electrophysiological measurements,
      expression of vector CFTR is usually assessed by RT-PCR. We have developed a CFTR
      expression vector, pCFAS, that simplifies the distinction of transgene-derived
      CFTR mRNA from endogenous mRNA. Two point mutations were introduced into CFTR
      cDNA which eliminated a SphI restriction site and created a new, unique AgeI
      restriction site. Neither mutation altered the predicted amino acid sequence of
      the protein. Restriction digestion of RT-PCR products from cells transfected with
      pCFAS allowed the differentiation of transgene and endogenous CFTR transcripts.
      To verify function of the mutated CFTR, the plasmid was transferred into freshly
      obtained nasal epithelial cells from CF patients ex vivo using cationic
      liposomes. Fluorescence microscopy using the halide-sensitive fluorophore SPQ
      demonstrated restoration of cAMP-mediated Cl- secretion. This plasmid will be
      useful for CFTR gene transfer studies in vitro and in vivo.

PMID- 8541846
TI  - Cardiac sodium channel mutations in patients with long QT syndrome, an inherited
      cardiac arrhythmia.
AB  - Long QT syndrome (LQT) is an inherited cardiac disorder that causes syncope,
      seizures and sudden death from ventricular tachyarrhythmias. We used single
      strand conformation polymorphism (SSCP) and DNA sequence analyses to identify
      mutations in the cardiac sodium channel gene, SCN5A, in affected members of four
      LQT families. These mutations include two identical intragenic deletions and two
      missense mutations. These data suggest that SCN5A mutations cause LQT. The
      location and character of these mutations suggest that this form of LQT results
      from a delay in cardiac sodium channel fast inactivation or altered voltage
      dependence of inactivation.

PMID- 8541847
TI  - Mutation of the glucagon receptor gene and diabetes mellitus in the UK:
      association or founder effect?
AB  - Recent evidence suggests that a mutation of the glucagon receptor (GCG-R) gene is
      involved in the development of type 2 diabetes in French patients. We have
      examined patients from three geographically distinct regions in the UK and found
      the GGT40 (Gly) to AGT40 (Ser) mutation to be present in 15/691 (2.2%) of
      patients with type 2 (non-insulin dependent) diabetes and 1/425 (0.2%) of
      geographically matched controls and have therefore replicated association of the
      GCG-R mutation with classical type 2 diabetes (Fisher's exact test p = 0.008). An
      increased frequency of the mutation of the GCG-R gene was also found in probands
      of type 1 (insulin dependent) diabetic multiplex (affected sib pair) families,
      (10/404, 2.5%). However, a lack of preferential transmission from parents
      heterozygous for the mutation, to affected type 1 diabetic sibs may suggest
      population stratification. This in turn cannot be excluded as an alternative
      explanation for the difference in frequency of the GCG-R gene mutation between
      subjects with type 2 diabetes and normal controls.

PMID- 8541848
TI  - The genes for a spliceosome protein (SAP62) and the anti-Mullerian hormone (AMH)
      are contiguous.
AB  - During an investigation of the regulatory potential of a region 5' of the mouse
      anti-mullerian hormone (Amh) gene, we identified a region of homology with the
      known cDNA sequence of a human spliceosome gene (SAP62). In mouse, the Sap62
      termination codon (TGA) is just 434 bp 5' of the Amh start of translation (ATG);
      in the human the equivalent distance is 789 bp. RNase protection analysis shows
      the majority of Sap62 transcripts use an uncommon polyadenylation signal (ATTAAA)
      lying in the intragenic region, 87 bp 3' of the TGA. This analysis also shows
      that Sap62 is transcribed in all tissues examined, whereas specific Amh
      transcription initiating 10 bp 5' of the ATG is limited to the developing testis
      of the fetus from 11.5 days post coitum and in the ovary from 3 days post partum.
      However, in all tissues a significant number of Sap62 transcripts fail to
      polyadenylate in the intragenic region and continue through the Amh locus. This
      implies that the Amh locus is in an open chromatin state in all tissues despite a
      requirement for precise regulation. Human SAP62 can now be mapped to HSA19p and
      mouse Sap62 to MMU10.

PMID- 8541849
TI  - Predominant neuronal expression of the gene responsible for dentatorubral
      pallidoluysian atrophy (DRPLA) in rat.
AB  - Dentatorubral and pallidoluysian atrophy (DRPLA) belongs to a group of
      trinucleotide diseases in humans associated with an expanded and unstable (CAG) >
      49 repeat within a gene of unknown function. Clinically, DRPLA presents with
      variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis
      and dementia. Hardly anything is known about the physiological function of the
      DRPLA gene and the pathological mechanisms causing neuronal cell death and
      leading to these symptoms. To analyze some of these aspects of the DRPLA gene we
      isolated the complete coding region of the rat DRPLA gene (rdrpla) and
      investigated its expression in different developmental stages of rodent tissues.
      The rdrpla gene shows 92% homology in amino acid sequence to the human gene. In
      rat the length of the (CAG)n repeat is reduced compared to the human (CAG)n block
      containing 7-34 repeats with an average of 15. Northern blot analysis revealed
      that in rodents the rdrpla gene is already expressed during embryo development.
      In addition this transcript is predominantly represented in neuronal tissues
      throughout all developmental stages investigated.

PMID- 8541850
TI  - Familial non-specific dementia maps to chromosome 3.
AB  - A significant minority of degenerative dementias lack distinctive inclusion
      bodies, plagues or tangles on pathological examination. Half of these cases have
      a positive family history of dementia. We have studied the largest published
      family with such a dementia and mapped the disease locus to a 12 cM region of
      chromosome 3 spanning the centromere. Haplotype analysis demonstrates a common
      region shared between all affected individuals between the markers D3S1284 and
      D3S1603. Like a number of other late onset neurodegenerative diseases, the
      disease presents at an earlier age when paternally inherited.

PMID- 8541851
TI  - Mapping of a distal form of spinal muscular atrophy with upper limb predominance
      to chromosome 7p.
AB  - An autosomal dominant distal form of spinal muscular atrophy mainly affecting the
      upper limbs with a mean age of onset of 17 years has been identified in a large
      Bulgarian family. Linkage of the above family to the spinal muscular atrophy type
      I, II and III locus on chromosome 5 has been excluded. In an attempt to map this
      disease gene we have analysed individuals of this family, with more than 140
      microsatellite polymorphic markers of the human genome. A maximum lod score of
      5.99 at theta = 0.007 has been obtained with locus D7S795. We have thus mapped
      the gene for this hereditary form of distal spinal muscular atrophy to chromosome
      7p.

PMID- 8541852
TI  - Localization of the Schwartz-Jampel syndrome (SJS) locus to chromosome 1p34-p36.1
      by homozygosity mapping.
AB  - Schwartz-Jampel syndrome (SJS, MIM 255800), also known as chondrodystrophic
      myotonia, is a rare autosomal recessive disorder characterized by generalized
      myotonia, skeletal abnormalities and facial dysmorphism. Using homozygosity
      mapping, we localized the SJS locus to chromosome 1p34-p36.1 in a 8 cM interval
      flanked by markers D1S199 and D1S234. Families of different ethnic backgrounds
      (Tunisia and South Africa) showed genetic linkage to the same locus. Moreover,
      one Algerian family also demonstrated evidence of genetic linkage to 1p34-p36.1.
      Taken altogether, our results suggest genetic homogeneity, at least in the group
      of families analyzed.

PMID- 8541853
TI  - Linkage of congenital, recessive deafness (DFNB4) to chromosome 7q31 and evidence
      for genetic heterogeneity in the Middle Eastern Druze population.
AB  - Clinically significant hearing loss affects 1 in 1000 infants and it is estimated
      that at least 50% of these cases are due to a genetic cause. Some forms of
      inherited deafness are syndromic and affected individuals have a specific pattern
      of additional features while in other families the deafness is non-syndromic and
      there is no other recognizable phenotype. Analysis of several large families with
      syndromic and non-syndromic forms of deafness have been used in genetic linkage
      analysis to identify genes or gene locations that cause deafness. Here, we
      describe a large Middle-Eastern Druze family with recessive non-syndromic
      deafness and demonstrate linkage between deafness in this family and human
      chromosome 7q31 with a lod score exceeding 5.5. This is the first evidence for a
      gene at this location that causes deafness. In addition, we found that deafness
      in three other Druze pedigrees, one related to the linked family, is not linked
      to this chromosomal location. This suggests that there are multiple nonallelic
      mutations for deafness in this genetic isolate.

PMID- 8541854
TI  - Consanguineous nuclear families used to identify a new locus for recessive non
      syndromic hearing loss on 14q.
AB  - Hearing impairment is inherited most frequently as an autosomal recessive
      isolated clinical finding (non-syndromic hearing loss, NSHL). Extreme
      heterogeneity and phenotypic variability in the audiometric profile preclude
      pooling of affected families and severely hamper gene mapping by conventional
      linkage analysis. However, in instances of consanguinity, homozygosity mapping
      can be used to identify disease loci in small nuclear families. This report
      demonstrates the power of this technique by identifying a locus for recessive
      NSHL on 14q (DFNB4).

PMID- 8541855
TI  - Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to
      type II Ehlers-Danlos syndrome (EDS II).
AB  - Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective
      tissue with skin, ligaments and blood vessels being the main sites affected. The
      commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and
      is characterized by joint hypermobility, cigarette paper scars, lax skin and
      excessive bruising. As yet no gene has been linked to EDS II, nor has linkage
      been established to a specific region of the genome. However, several candidate
      genes encoding proteins of the extracellular matrix have been excluded. Using an
      intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1
      gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum
      LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single
      large pedigree.

PMID- 8541856
TI  - Localization of the gene for progressive bifocal chorioretinal atrophy (PBCRA) to
      chromosome 6q.
AB  - Progressive bifocal chorioretinal atrophy (PBCRA) is a rare, autosomal dominant
      congenital chorioretinal dystrophy. We have performed genetic linkage analysis on
      a five-generation British pedigree. Two-point linkage analysis showed significant
      linkage with nine microsatellite marker loci mapping to chromosome 6q. Multipoint
      analysis gave a maximum lod score of 11.8 (theta = 0.05) between D6S249 and
      D6S283. This region overlaps with that to which the gene for North Carolina
      macular dystrophy (MCDR1) has been assigned. However, given the range of
      differences in phenotype between these two retinal disorders, it is likely that
      different mutation mechanisms are responsible for each disease.

PMID- 8541857
TI  - The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome
      6q.
AB  - Progressive myoclonus epilepsy of the Lafora type (Lafora's disease) is an
      autosomal recessive disease characterized by epilepsy, myoclonus, dementia, and
      periodic acid-Schiff-positive intracellular inclusion bodies. The inclusion
      deposits consist of branched polysaccharides (polyglucosans) but the responsible
      biochemical defect has not been identified. Onset is during late childhood or
      adolescence and the disease leads to a fatal outcome within a decade of first
      symptoms. We studied nine families in which Lafora's disease had been proven by
      biopsy in at least one member. In order to locate the responsible gene, we
      screened the human genome with microsatellite markers spaced an average of 13 cM.
      We used linkage analysis in all nine families and homozygosity mapping in four
      consanguineous families to define the Lafora's disease gene region. Two point
      linkage analysis resulted in a total peak lod score of 10.54 for marker D6S311.
      Six additional chromosome 6q23-25 microsatellites yielded lod scores ranging from
      5.92 to 9.60 at theta m = f = 0. An extended pedigree with five affected members
      independently proved linkage with peak lod scores over 3.8 at theta m = f = 0 for
      D6S292, D6S403, and D6S311. The multipoint one-lod-unit support interval covered
      a 2.5 cM region surrounding D6S403. Homozygosity mapping defined a 17 cM region
      in chromosome 6q23-25 flanked by D6S292 and D6S420 that contains the Lafora's
      disease gene.

PMID- 8541858
TI  - Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to
      chromosome 10q23.1-q23.3.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized
      by the triad of tyrosinase-positive oculocutaneous albinism, bleeding diathesis
      due to storage-pool deficiency of platelets, and a lysosomal ceroid storage
      disease. The disorder is particularly frequent in Puerto Rico and in an isolated
      village in the Swiss Alps. We have used a linkage disequilibrium mapping approach
      to localize the HPS gene in both of these groups to a 0.6 centiMorgan interval in
      chromosome segment 10q23.1-q23.3. These results indicate that the Puerto Rican
      and Swiss forms of HPS are either allelic or that they result from mutations in
      very closely linked genes in this region. This region of distal chromosome 10q is
      syntenic to the region of mouse chromosome 19 that includes 'pale ear' (ep) and
      'ruby-eye' (ru), which must be considered as potential murine homologues to human
      HPS.

PMID- 8541859
TI  - Identification of two new KCNA1 mutations in episodic ataxia/myokymia families.

PMID- 8541860
TI  - Constant rearrangement of the CMT1A-REP sequences in HNPP patients with a
      deletion in chromosome 17p11.2: a study of 30 unrelated cases. The French CMT
      Collaborative Research Group.

PMID- 8541861
TI  - Osteoblastic cells derived from isolated lesions of fibrous dysplasia contain
      activating somatic mutations of the Gs alpha gene.

PMID- 8541862
TI  - A 30 kb deletion within the elastin gene results in familial supravalvular aortic
      stenosis.

PMID- 8541863
TI  - Spontaneous deletion in the FMR1 gene in a patient with fragile X syndrome and
      cherubism.

PMID- 8541864
TI  - A deletion and an insertion in the alleles for the xeroderma pigmentosum (XPA)
      DNA-binding protein in mildly affected patients.

PMID- 8541865
TI  - Multiple independent occurrence of the 3243 mutation in mitochondrial
      tRNA(leuUUR) in patients with the MELAS phenotype.

PMID- 8541866
TI  - Intronic point mutation in the IL2RG gene causing X-linked severe combined
      immunodeficiency.

PMID- 8541867
TI  - Recent molecular advances in dysmorphology.
AB  - Recent advances in the mapping and isolation of genes responsible for birth
      defects are reviewed. Groups of disorders where rapid progress has been made
      include bone dysplasias, craniosynostoses and craniofacial syndromes.

PMID- 8541868
TI  - Syndromal mental retardation due to mutations in a regulator of gene expression.
AB  - Mental handicap is a common clinical problem that has been a relatively neglected
      area of research. Though the causes are varied and complex, molecular biologists
      are making progress in understanding the mechanisms in some cases, particularly
      where there are distinguishing phenotypic or genetic markers. The fortuitous
      association of alpha thalassaemia with a form of mental retardation has allowed
      us to define a specific X-linked syndrome (ATR-X). Positional cloning was used to
      define a disease interval and examination of candidate genes demonstrated that
      mutations in a gene, XH2, showing homology to the SNF2 superfamily were
      responsible for this syndrome. The complex ATR-X phenotype suggests that this
      gene, when mutated, down-regulates the expression of several genes including the
      alpha-globin genes indicating that it could be a global transcriptional
      regulator. It is conceivable that this mechanism is involved in other forms of
      syndromal mental retardation.

PMID- 8541869
TI  - Dystrophin-associated proteins in muscular dystrophy.
AB  - Dystrophin-associated proteins (DAPs) are classified into a few groups, namely,
      those comprising of dystroglycan complex, sarcoglycan complex, syntrophin complex
      and others. Subsarcolemmal actin filaments are connected to laminin in the
      basement membrane through dystrophin and the dystroglycan complex. This system
      may function to protect muscle fibers from mechanical damage. Furthermore, the
      sarcoglycan complex is associated with the system. Defects in the components of
      the protection system or the sarcoglycan complex or both are characteristically
      found in various muscular dystrophies. The roles of the syntrophin complex are
      meagerly understood. In this review, the possible roles of laminin, DAPs and
      dystrophin in each dystrophy are explained.

PMID- 8541870
TI  - PAX genes: what's new in developmental biology and cancer?
AB  - PAX genes encode nuclear transcription factors which are rapidly becoming
      regarded as major controllers of developmental processes in both vertebrates and
      invertebrates. Mutations in murine Pax genes underlie three natural mouse alleles
      and two corresponding human syndromes. Murine Pax genes have been shown to be
      proto-oncogenes. Furthermore, human PAX genes have recently been demonstrated to
      play an influential part in some common human cancers. The diversity in effects
      of PAX genes reflects that of their structure. All encode a DNA-binding domain
      termed the paired domain and in addition some also encode a second binding domain
      -the paired type homeobox.

PMID- 8541871
TI  - Familial hypertrophic cardiomyopathy: a genetic model of cardiac hypertrophy.
AB  - Familial hypertrophic cardiomyopathy is an autosomal dominant disorder
      manifesting as cardiac hypertrophy in the absence of increased cardiac work load,
      which has been studied as a model of myocardial hypertrophy in humans.
      Hypertrophic cardiomyopathy is genetically heterogeneous with three known disease
      genes and two further mapped loci. The disease-genes encode contractile proteins
      of the thick and thin filaments of the sarcomere: the beta cardiac myosin heavy
      chain gene on chromosome 14q11, the alpha tropomyosin gene on chromosome 15q2 and
      the cardiac troponin T gene on chromosome 1q3. Other disease loci have been
      mapped to chromosome 11p13-q13 and 7q3. In each known disease-gene a number of
      different mutations have been identified; these are missense mutations, or
      mutations leading to modest alterations of peptide structure, but not null
      alleles. Specific mutations are associated with different disease severity and
      may provide diagnostic and prognostic information not available from clinical
      assessment. Genetic and functional data suggest that mutations which cause
      hypertrophic cardiomyopathy act as dominant negative alleles that impair cross
      bridge cycling and contractile function and interfere with sarcomere assembly.

PMID- 8541872
TI  - Norrie disease and MAO genes: nearest neighbors.
AB  - The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region
      of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship
      is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes
      appear to have arisen by tandem duplication of an ancestral MAO gene, but their
      positional relationship to NDP appears to be random. Distinctive X-linked
      syndromes have been described for mutations in the MAOA and NDP genes, and in
      addition, individuals have been identified with contiguous gene syndromes due to
      chromosomal deletions which encompass two or three of these genes. Loss of
      function of the NDP gene causes a syndrome of congenital blindness and
      progressive hearing loss, sometimes accompanied by signs of CNS dysfunction,
      including variable mental retardation and psychiatric symptoms. Other mutations
      in the NDP gene have been found to underlie another X-linked eye disease,
      exudative vitreo-retinopathy. An MAOA deficiency state has been described in one
      family to date, with features of altered amine and amine metabolite levels, low
      normal intelligence, apparent difficulty in impulse control and cardiovascular
      difficulty in affected males. A contiguous gene syndrome in which all three genes
      are lacking, as well as other as yet unidentified flanking genes, results in
      severe mental retardation, small stature, seizures and congenital blindness, as
      well as altered amine and amine metabolites. Issues that remain to be resolved
      are the function of the NDP gene product, the frequency and phenotype of the MAOA
      deficiency state, and the possible occurrence and phenotype of an MAOB deficiency
      state.

PMID- 8541873
TI  - Molecular genetics of retinitis pigmentosa.
AB  - Hereditary degenerations and dysfunctions of the retina are an extremely
      heterogeneous group of diseases. This summary deals with recent advances in the
      molecular genetics of a subset of those disorders, namely, those encompassed
      under the diagnosis 'retinitis pigmentosa'. Over 20 loci where mutations cause
      retinitis pigmentosa have been mapped; the review focuses on the seven retinitis
      pigmentosa loci that have been identified.

PMID- 8541874
TI  - Autosomal dominant polycystic kidney disease: molecular analysis.
AB  - Using a positional cloning approach the major autosomal dominant polycystic
      kidney disease (ADPKD) gene (PKD1) has been identified on chromosome 16: a
      disease associated chromosome translocation was instrumental in its
      identification. Study of the PKD1 gene has been complicated because most of the
      gene lies in a genomic region reiterated elsewhere on the same chromosome. The
      duplicate area contains three genes which share substantial homology with PKD1
      and generate polyadenylated transcripts. Most PKD1 mutations have so far been
      detected in the single copy, 3' end of the gene, but a group of patients with
      deletion of PKD1 and the adjacent TSC2 gene, which have severe infantile
      polycystic kidney disease, have also been characterised. The full length
      transcript of PKD1 (approximately 14 kb) has now been cloned and is predicted to
      encode a protein, polycystin, of 4302/3 aa. Polycystin contains multiple
      extracellular domains including leucine rich repeats, a C-type lectin,
      immunoglobulin and fibronectin type III-like domains and has a C terminal region
      which is likely associated with the membrane. These homologies indicate that
      polycystin is a cell-cell/matrix interaction protein.

PMID- 8541875
TI  - DNA methylation in early development.
AB  - Several lines of evidence strongly suggest that DNA methylation is involved in
      embryo development. Perhaps the most direct evidence comes from experiments with
      methyltransferase deficient mice. Embryos that express low levels of the
      maintenance methyltransferase do not develop to term and die at the 5 to 20
      somite stage corresponding to the level of the enzyme. In the mouse, dramatic
      methylation changes have been observed during the early steps of embryo
      development. Most genes are subject to a process of active demethylation starting
      promptly after fertilization. Except for a small number of methylated CpG sites
      in imprinted genes the vast majority of the sites are unmethylated by the stage
      of cavitation (16 cell). Such genome-wide demethylation may signify an erasure of
      epigenetic information originating in the highly differentiated gametes. This
      erasure may be essential for the establishment of a pluripotent state, before
      specific cell lineages can be determined. The process of laying down a new
      developmental program involves, initially, global de novo methylation at the
      stage of pregastrulation followed by gene specific demethylations associated with
      the onset of activity of these genes. CpG islands characteristic of housekeeping
      genes, appear to be protected from the global de novo methylation. An exception
      to this rule is the hypermethylation of CpG islands in X-linked housekeeping
      genes on the inactive X chromosome and of specific differentially methylated CpG
      sites in imprinted genes. Primordial germ cells escape the global de novo
      methylation which takes place at the pregastrula stage and undergo a very similar
      de novo methylation process in the differentiated gonads (15.5-18.5 days post
      coitum), forming the methylation patterns which are specific to the gametes.
      Specific demethylations then form a terminal methylation pattern which is then
      clonaly inherited in the soma and erased after fertilization.

PMID- 8541876
TI  - Uniparental disomy in humans: development of an imprinting map and its
      implications for prenatal diagnosis.
AB  - Uniparental disomy (UPD) in humans is caused primarily by meiotic nondisjunction
      events, followed by trisomy or monosomy 'rescue'. The majority of cases appear to
      be associated with advanced maternal age, and may be initially detected as mosaic
      trisomies during routine prenatal diagnosis by chorionic villus sampling or
      amniocentesis. In addition, structural abnormalities including Robertsonian
      translocations, reciprocal translocations and supernumerary marker chromosomes
      appear to be associated with an increased risk of UPD. Predicting the phenotypic
      effects of UPD is complex, as three independent factors are involved: (i) effects
      of trisomy on the placenta or the fetus; (ii) autosomal recessive disease due to
      reduction to homozygosity; and (iii) imprinted gene effects for some chromosomes.
      To date, UPD in humans has been reported for 25 of the 47 possible uniparental
      types. Imprinting effects have been established with certainty for four human
      chromosomes that have homology to mouse chromosomes which have been shown to have
      significant phenotypic effects in uniparental animals. A normal phenotype has
      been reported for 14 other UPD types. Thus, collection of data on UPD cases in
      humans is providing an imprinting map analogous to the experimentally derived
      imprinting map in mouse. This human imprinting map has important clinical
      implications, particularly in the area of prenatal diagnosis.

PMID- 8541877
TI  - Epigenetic regulation of gene expression: the effect of altered chromatin
      structure from yeast to mammals.
AB  - Epigenetic gene regulation refers to different states of phenotypic expression
      caused by differential effects of chromosome or chromatin packaging rather than
      by differences in DNA sequence. Examples of epigenetic regulation can be found in
      organisms as diverse as the yeasts Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, the fruit fly Drosophila melanogaster, the nematode
      Caenorhabditis elegans, and mammals. Three major types of epigenetic regulation
      are considered in this review: dosage compensation, imprinting and position
      effect variegation. While the specific details and mechanisms of each is quite
      different, they all involve either local or extensive alterations in chromatin
      structure. A number of genes implicated in epigenetic regulation have been
      isolated and their products identified as proteins or RNA molecules involved at
      various levels in DNA, chromatin or chromosome binding. While in general our
      understanding of mammalian epigenetic phenomena is not as advanced as that in
      model systems, the detailed molecular and genetic understanding of processes
      responsible for conditional gene silencing in invertebrate systems provides
      strong models for consideration of such effects in human and mouse genetics.

PMID- 8541878
TI  - Compartmentalization of specific pre-mRNA metabolism: an emerging view.
AB  - It is increasingly recognized that the mammalian interphase nucleus contains a
      number of non-membranous compartments in which macromolecules associated with
      different nuclear functions concentrate. This review focuses on the function of a
      major compartment consisting of domains highly enriched in pre-mRNA splicing
      components and poly (A) RNA, commonly identified by the splicing factor, SC-35.
      RNA synthesis, as judged interdomain space. However, uridine labels several types
      of nuclear RNA, only a fraction of which is pre-mRNA, and such studies cannot
      address the question of whether specific genes are transcribed in specific
      places. Similarly, interpretations of transcriptional inhibition studies are
      compromised by the global impact that inhibition has on nuclear structure and
      function, and by conflicting results. Localization of specific protein coding
      genes or RNAs circumvents these limitations. For several sequences studied thus
      far, a non-random relationship to SC-35 domains has been observed, with most, but
      not all, active genes encoding intron-containing pre-mRNAs showing a very high
      degree of association. In some cases this was directly demonstrated to be the
      site of transcription and processing. Consistent with earlier uridine
      incorporation studies, we have found that transcription occurs at the outer edge
      of the SC-35 domain, likely corresponding to the border of ultrastructures termed
      interchromatin granule clusters. These preliminary glimpses into gene
      localization strongly argue for a sequence-specific spatial association of some
      transcriptionally active genes with SC-35 domains, and suggest an integrated
      functional organization of the genome with these nuclear compartments enriched in
      splicing factors and poly (A) RNA.

PMID- 8541879
TI  - Disorders of peroxisome biogenesis.
AB  - The peroxisome is a ubiquitous, subcellular organelle containing more than 50
      matrix enzymes that participate in a diverse array of metabolic pathways. Failure
      to assemble normal peroxisomes is the cellular hallmark of Zellweger syndrome and
      other human disorders of peroxisome biogenesis. Identification of the genes
      required for peroxisome biogenesis is proceeding at a rapid pace helped
      immeasurably by work in other species, particularly various yeasts. The ultimate
      goals of this effort are to identify all of these genes and to understand how
      their protein products interact to produce normal appearing and functioning
      peroxisomes. Attainment of these goals will lead to a better understanding of the
      peroxisome biogenesis disorders, their pathophysiology and treatment.

PMID- 8541880
TI  - Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and
      related disorders.
AB  - The extracellular microfibril, 10-14 nm in diameter, performs a number of
      functions, including serving as the scaffolding for deposition of tropoelastin to
      form elastic fibers. A variety of proteins compose the structure of microfibrils,
      the most prominent of which are the two fibrillins. Fibrillin-1 is encoded by
      FBN1 on human chromosome 15q21 and fibrillin-2 is encoded by FBN2 on 5q23. Each
      fibrillin monomer contains a large number of epidermal growth factor-like motifs,
      most capable of binding calcium ions, and a few motifs resembling the binding
      protein for transforming growth factor beta. In vitro polymerization of fibrillin
      monomers produces 'beads on a string' structures that look on electron microscopy
      much like microfibrils purified from the extracellular matrices of a variety of
      tissues. Mutations in FBN1 produce Marfan syndrome, a pleiotropic autosomal
      dominant connective tissue disorder with prominent manifestations in the
      skeleton, eye and cardiovascular system. A number of conditions related to Marfan
      syndrome are also due to FBN1 mutations. Contractural arachnodactyly is due to
      mutations in FBN2. In this paper we review the published mutations in these
      genes, preliminary results of genotype-phenotype correlations, and speculations
      regarding molecular pathogenesis.

PMID- 8541881
TI  - Inherited breast and ovarian cancer.
AB  - An estimated 5 to 10% of all breast and ovarian cancer is attributable to
      inherited mutations in two highly penetrant autosomal dominant susceptibility
      genes, BRCA1 and BRCA2. BRCA1 confers higher risk of ovarian cancer and BRCA2
      much higher risk of male breast cancer. With the exception of missense mutations
      in the RING finger near the amino terminus of BRCA1, virtually all germline
      mutations in the gene cause the novel BRCA1 protein to be prematurely truncated.
      Approximately 90% of breast tumors in BRCA1 families, 50% of unselected breast
      tumors and 65-80% of unselected ovarian tumors have lost one allele of BRCA1 by
      somatic deletion. Very few tumors have detectable somatic point mutations in
      BRCA1. Inhibition of BRCA1 expression in mammary epithelial cell lines also
      suggests that BRCA1 may act as a tumor suppressor. The biological function of
      BRCA1 is still unknown, although identification of a patient homozygous for an
      inherited BRCA1 mutation suggests that the gene's function may be essential only
      to specific tissues. At least two other genes, P53 and the androgen receptor, are
      responsible for inherited predisposition to breast cancer in rare families.
      Several epidemiologic studies suggest that individuals carrying rare alleles at a
      minisatellite flanking the HRAS locus are at increased risk of cancer, including
      breast cancer. Finally, preliminary epidemiologic studies also suggest that
      individuals heterozygous for mutations in the ataxia telangiectasia gene may be
      at increased risk of breast cancer.

PMID- 8541882
TI  - Isolation and sequence analysis of a cDNA clone for a pyrethroid inducible
      cytochrome P450 from Helicoverpa armigera.
AB  - The complete coding sequence and parts of the 3' and 5' noncoding regions of a
      mRNA coding for a cytochrome P450 from Helicoverpa armigera have been obtained.
      The sequence is most similar to members of family CYP6, in particular that
      obtained from Papilio polyxenes, CYP6B1, and has been labeled CYP6B2 accordingly.
      The original cDNA was obtained by screening a cDNA library with an
      oligonucleotide specific for the amino acid sequence surrounding the cysteine
      residue involved in heme binding, present in the other known insect sequences.
      This sequence is also present in mammalian members of family CYP3. The highly
      conserved nature of this particular sequence suggests that this approach may
      allow the easy and direct identification of cDNA clones specific for members of
      this particular cytochrome P450 family from a wide variety of species of
      invertebrates and, possibly, vertebrates. The cDNA hybridizes to two major mRNAs
      of 2.1 and 1.8 kb in length. Induction studies indicate that the smaller mRNA is
      inducible by phenobarbital while the larger mRNA is inducible by the pyrethroid
      insecticide permethrin. Both the evolution of this particular family of
      cytochrome P450 genes and its potential involvement in the development of
      resistance to pyrethroids is discussed.

PMID- 8541883
TI  - Processing of procathepsin from Musca domestica eggs.
AB  - The major source of amino acids for insect embryos are yolk proteins which
      accumulate in developing oocytes and are hydrolyzed during embryogenesis. Studies
      on Musca domestica embryogenesis indicated that a cathepsin B-like proteinase is
      responsible for yolk protein degradation (Ribolla et al., 1993). In this study,
      we report the purification of mature cathepsin and show that it is made up of a
      single 41 kDa polypeptide chain. The Musca domestica cathepsin NH2-terminal 11
      residue sequence was determined (Ala-Pro-Lys-Tyr-Val-Asp-Tyr-Gly-Glu-Asn-Glu) and
      reveals homology with other cathepsins of the papain family. Experiments using
      serum anti-cathepsin show that the enzyme is stored in oocytes as a 55 kDa
      zymogen. The activation of the zymogen occurs in vitro only at low pH. In vitro
      activation in the presence of cysteine protease inhibitors is blocked at an
      intermediary polypeptide of 48 kDa. Kinetic studies of this activation process at
      pH 3.5 and 4.6 show that the zymogen is processed in a manner similar to that of
      pepsin (Foltmann, 1986) and papain (Vernet et al., 1991). We propose that Musca
      domestica cathepsin zymogen activation occurs in two steps. First, an
      intramolecular cleavage of the procathepsin polypeptide chain (55,000), induced
      by low pH gives rise to an intermediary polypeptide (48,000) which then undergoes
      autolysis to produce the mature enzyme (41,000).

PMID- 8541884
TI  - Prostaglandin biosynthesis and subcellular localization of prostaglandin H
      synthase activity in the lone star tick, Amblyomma americanum.
AB  - We report on prostaglandin (PG) biosynthesis in the lone star tick, Amblyomma
      americanum. In vitro preparations of whole female ticks and internal tissues were
      competent to biosynthesize four PGs: PGA2/PGB2, PGD2, PGE2, PGF2 alpha. PGA2/PGB2
      was the major product under optimal conditions. PG biosynthesis by whole tick and
      internal tissues were sensitive to incubation conditions including, protein
      concentration, time, temperature, pH, and presence of a co-factor cocktail
      composed of reduced glutathione, hydroquinone, and hemoglobin. Under standard
      assay conditions, 2 mg/ml protein were incubated at pH 8.0 for 2 min at 32
      degrees C. PG biosynthesis was inhibited by indomethacin, a potent cyclooxygenase
      inhibitor in mammalian systems. Internal tissue preparations were fractionated
      into cytosolic and microsomal preparations by ultracentrifugation. PG
      biosynthetic activity was detected in both fractions. The subcellular
      distribution of PG biosynthetic activity in ticks is similar to other
      invertebrates, but quite different from mammals, in which PG biosynthetic
      activity is almost exclusively localized in the microsomal fractions. PGH
      synthase-2 was detected in the microsomal fraction on western blot analysis.
      These results suggest that the lone star tick is competent to biosynthesize PGs.
      These compounds may contribute to the success of tick feeding ecology by
      attenuating the defense responses of vertebrate hosts during lengthy feeding
      periods.

PMID- 8541885
TI  - Intracellular signal transduction of PBAN action in the common cutworm,
      Spodoptera litura: effects of pharmacological agents on sex pheromone production
      in vitro.
AB  - Pheromone biosynthesis activating neuropeptide (PBAN) regulates sex pheromone
      production in the pheromone glands of many species of female moths. In order to
      probe the biochemical steps as well as underlying mechanisms regulated by PBAN,
      we have tested the effects of pharmacological agents on sex pheromone production
      of the common cutworm, Spodoptera litura, using an in vitro assay. Among the
      pharmacological agents we tested, ionomycin (calcium ionophore) alone stimulated
      sex pheromone production, while LaCl3 (calcium channel blocker), W-7,
      trifluoperazine (calmodulin inhibitor), NaF, and p-nitrophenyl phosphate
      (phosphatase inhibitor) suppressed the pheromone production by a pheromonotropic
      peptide, TKYFSPRLamide. By contrast, forskolin (adenylate cyclase activator),
      phorbol 12-myristate 13-acetate (protein kinase C activator), and cyclic
      nucleotides alone failed to stimulate sex pheromone production. These results
      suggest that Ca2+/calmodulin complex and phosphoprotein phosphatase are involved
      in the signal transduction of PBAN action in S. litura.

PMID- 8541886
TI  - Carboxydipeptidase from Boophilus microplus: a "concealed" antigen with
      similarity to angiotensin-converting enzyme.
AB  - A protein, Bm91, which was first identified as a protective vaccine antigen from
      the tick Boophilus microplus, has regions of very strong amino acid sequence
      similarity to mammalian carboxydipeptidases or angiotensin converting enzymes
      (ACE; E.C. 3.4.15.1). This protein is now shown to share many biochemical and
      enzymatic properties with mammalian carboxydipeptidases. It is enzymatically
      active in a conventional assay for ACE using hippuryl-Gly-Gly as substrate. The
      hydrolysis of the C-terminal nonapeptide of the insulin B chain proceeds by
      sequential removal of carboxy-terminal dipeptides. The similarities extend to the
      dependence of activity on pH and added salt. Bm91 is inhibited by two well
      characterized inhibitors of the mammalian enzymes, the drug Captopril and a
      nonapeptide, and the inhibition occurs in similar concentration ranges to those
      effective with the mammalian enzymes. However, the natural substrates of the tick
      enzyme are unknown. Angiotensin I itself is a poor substrate and the enzyme's
      natural substrates are likely to be one or more of the pharmacologically active
      peptides occurring in insects and arthropods.

PMID- 8541887
TI  - Complete cDNA-sequence of the receptor responsible for arylphorin uptake by the
      larval fat body of the blowfly, Calliphora vicina.
AB  - In late larvae of the blowfly Calliphora vicina the storage protein arylphorin is
      selectively taken up by the fat body cells from the haemolymph. We have
      demonstrated that arylphorin incorporation is mediated by a specific membrane
      bound receptor which is activated by 20-hydroxyecdysone. In this study we report
      the construction of a cDNA expression library from mRNA isolated from 8-day-old
      Calliphora larvae. Using affinity-purified antibodies against the arylphorin
      receptor we identified two cDNA clones of 4044 and 4043 bp, respectively. Both
      clones code for a 1253 amino acid protein with a deduced molecular mass of 142
      kDa, the potential arylphorin receptor precursor, as confirmed by
      immunoprecipitation of translation products in vitro. Southern blot analysis
      indicated a single copy gene with multiple alleles; Northern blotting revealed a
      single mRNA of about 4.5 kb that appeared stage specifically from day 4 to day 8
      during larval development. The deduced amino acid sequence exhibits significant
      similarities to arylphorin, the ligand, as well as to Fbp 1, the product of an
      ecdysteroid-inducible gene in Drosophila melanogaster larval fat body.

PMID- 8541888
TI  - Characterization and cloning of insecticidal peptides from the primitive weaving
      spider Diguetia canities.
AB  - Three potent insecticidal peptide toxins were purified from the venom of the
      primitive weaving spider, Diguetia canities. The toxins share significant
      homology (> 40%) in their amino acid sequences and are of related size (masses of
      6371-7080 Da). In lepidopteran larvae, the toxins cause a progressive spastic
      paralysis, with 50% paralytic doses (PD50S) ranging from 0.38 to 3.18 nmol/g,
      suggesting them to be among the most potent insecticidal compounds yet described
      from arthropod venoms. The most potent of these toxins, DTX9.2, was cloned using
      a reverse transcription-polymerase chain reaction (RT-PCR). The cDNA encodes a 94
      amino acid precursor which is processed to the active 56 amino acid peptide by
      removal of a signal and propeptide sequence. The gene encoding DTX9.2 was
      isolated and characterized. The transcriptional unit spans 5.5 kilobases and is
      segregated into five exons. DNA sequences upstream from the first exon contain a
      TATA box and two palindromic sequences (one with homology to a CAAT consensus)
      which together may constitute a functional promoter. The highly segmented gene
      structure observed for this small peptide suggests that a mechanism such as exon
      shuffling may have played a role in the evolution of this toxin family.

PMID- 8541889
TI  - On the morphological diagnostics and host specificity of the Sarcocystis species
      of some domesticated and wild bovini (cattle, banteng and bison).
AB  - Sarcocysts of Sarcocystis cruzi, S. hominis and S. hirsuta were described and
      compared by means of light (LM) and transmission electron microscopy (TEM) from
      cattle, bantengs (born in a zoo) and bisons (born in zoo). No morphological
      differences were observed in the three forms of sarcocysts from each of the three
      host species. The morphological criteria of the three species were discussed and,
      partly, newly defined. S. cruzi can easily be distinguished from the other two
      species. It shows 6-13 micron long hair-like villar protrusions in the freshly
      extracted sarcocyst, has large compartments often bump-like bulged out (by LM, in
      the fresh state), and a "thin cyst wall" ( < 1 micron; LM, histology). TEM
      investigation is not necessary in most cases. S. hominis and S. hirsuta: with a
      "thick, radially striated" and 2.5-9.0 micron high cyst wall (LM). S. hominis can
      be most reliably determined by means of TEM: the villar protrusions arise with a
      broad basis from the cyst surface, are finger-like in the outline and have
      microfilaments in the core. LM: the villar protrusions are broadly seated on the
      cyst surface, without optical interruption. Likewise, S. hirsuta can be
      determined most reliably by TEM (in some cases also in semithin sections): the
      villar protrusions are club- or bulb-shaped in the outline, with a stalklet at
      the base and with microfilaments and large osmiophilic granules in the interior.
      LM (best in the fresh state): the palisade of villar protrusions often shows a
      bright or dotted horizontal line in the middle and a basal line with dark dots,
      arranged like a string of pearls.

PMID- 8541890
TI  - Neosporosis and toxoplasmosis-associated paralysis in dogs in Costa Rica.

PMID- 8541891
TI  - Biting activity of the malaria vector, Anopheles culicifacies, on man and cattle
      in Doon valley, India.
AB  - In the present study, the information about biting time and activity of a malaria
      vector, Anopheles culicifacies on man and cattle in Doon valley has been
      mentioned. The maximum biting activity, 22.4 percent in human bait indoor and
      20.5 percent in human bait outdoor was noted between 22.00-23.00 h in the night.
      However, the biting activity on animal bait (calf) was noted maximum in the mid
      night at 24.00-01.00 h.

PMID- 8541892
TI  - Length-weight relationship of Ligula intestinalis plerocercoids in adult silver
      bream and discussion on estimation of the parasite age.
AB  - The paper comprises an evaluation of Ligula intestinalis infection in adult
      silver bream (Blicca bjoerkna), from the Nove Mlyny Reservoirs (Czech Republic),
      from 1991 to 1993. The prevalence (mean 4.39%) and intensity (mean 1.39 spec.) of
      infection were very low, ranging from 1.48% (1.11 spec.) in April-May to 11.52%
      (1.36 spec.) in November-December. The length-weight relationship of single
      infection plerocercoids was characterized by the regression and correlation
      coefficients of linear and exponential regressions. The lowest weight and mean
      lengths of plerocercoids were found in April-May. According to the length and
      weight of plerocercoids in our collection those specimens were preliminary
      separated into 0+ to 5+ age classes. It is supposed that the longevity of the
      longest specimens of L. intestinalis plerocercoids attain the same age as their
      intermediate host (silver bream). The longest plerocercoid attained the body
      length of 1,006 mm and the weight of 32.0 g.

PMID- 8541893
TI  - Effect of temperature and humidity on longevity of unfed adults and on
      oviposition of engorged females of Dermacentor reticulatus (Ixodidae).
AB  - The effect of ambient temperature and relative humidity on longevity of unfed
      adult ticks and on oviposition of engorged female ticks of Dermacentor
      reticulatus was examined. The 50% mortality time of unfed adult ticks, incubated
      at 5 degrees C, 10 degrees C, 20 degrees C and 27 degrees C and humidities of
      15%, 50% and 100%, increased irrespective of their sex with rising relative
      humidity and decreasing temperature. It was longest at 5 degrees C and 100% r.h.
      being 617.8 days and shortest at 27 degrees C and 15% r.h. amounting only to 33.6
      days. All unfed ticks survived an incubation of 150 days at -10 degrees C and
      15%, 50% and 100% r.h. as well as an exposure of 180 days at 0 degrees C and 100%
      r.h. At 0 degrees C the percent survival was 75% for the males and 40% for the
      females at 50% r.h. but 100% for males and 95% for the females at 15% r.h. after
      exposure of 180 days. Oviposition of engorged females occurred at a temperature
      range of 10-27 degrees C, at 10 degrees C merely at 50% and 100% r.h. The
      percentage of ovipositioning females amounted to at least 80% apart from 10
      degrees C and 50% r.h. being only 10%. The egg index and the egg conversion index
      as well as the larvae index and the larvae conversion index generally increased
      with rising temperature and relative humidity. The indices were lowest at 10
      degrees C and 50% r.h. and were highest at 20 degrees C and 27 degrees C at 100%
      r.h. The reproduction capability of engorged female ticks, held at -10 degrees C,
      0 degrees C and 5 degrees C and 15%, 50% and 100% r.h. and transferred to 20
      degrees C and 95% r.h., persisted for 10 weeks at -10 degrees C and for 2 weeks
      at 0 degrees C at the most, but for at least 20 weeks at 5 degrees C. There were
      no significant differences of the preoviposition periods, egg indices and larvae
      indices as well as of the minimum embryonic developmental times and hatching
      rates with regard to the preceding incubation conditions and the length of the
      ticks' exposure.

PMID- 8541894
TI  - Dynamics of endoparasites in farmed fallow deer (Dama dama) from birth to
      puberty.
AB  - Rectal faecal samples from farmed fallow deer were examined for eggs, larvae and
      oocysts of gastro-intestinal and pulmonary parasites from July 1992, then the
      fawns were 6 weeks old, to September 1993 in four weekly intervals. The
      investigations showed a succession of species: Trichuris spp., Nematodirus
      roscidus and Capillaria bovis had their peaks in egg output in August 1992,
      September 1992 and February 1993, respectively. After reaching peaks the faecal
      output of Trichuris spp. and Nematodirus roscidus eggs showed a marked decline.
      The shedding of Dictyocaulus larvae had its highest peak in November 1992 and a
      smaller one in June 1993. The excretion of trichostrongyle eggs (other than
      Nematodirus roscidus), eggs of strongylids and Eimeria oocysts did not show well
      defined seasonal dynamics.

PMID- 8541895
TI  - Use of a monoclonal antibody against the antigen B of Echinococcus granulosus for
      purification and detection of antigen B.
AB  - A monoclonal antibody directed against the 8 kDa subunit of antigen B of
      Echinococcus granulosus was raised. This antibody was used for purification of
      antigen B by affinity chromatography. SDS-PAGE and immunological analysis of the
      purified antigen B demonstrated that the 8 kDa antigen B subunit was purified to
      homogeneity. The purified antigen retained its strong immunoreactivity in ELISA
      using human hydatid sera. Furthermore, a sandwich ELISA was established for
      detection of antigen B from hydatid cysts. The usefulness of this test system was
      demonstrated by the detection of antigen B in human hydatid cyst fluids, thus
      confirming the diagnosis of an echinococcal disease.

PMID- 8541896
TI  - Immunodiagnosis of Taenia saginata in cattle using hydrophobic antigens from T.
      hydatigena metacestode cyst fluid.
AB  - Hydrophobic fractions isolated from cyst fluid of Taenia hydatigena metacestodes,
      obtained from naturally infected goats from Tanzania, were used in an indirect
      ELISA and in immunoblot (Western or dot blot) procedures. The use of the most
      hydrophobic fractions of the cyst fluid proved to result in a better diagnostic
      discrimination in ELISA than the more hydrophilic fractions. Best diagnostic
      ratio between responses from T. saginata infected and non-infected cattle was
      achieved when using horse-radish peroxidase-labelled sheep antibovine IgG1 as the
      conjugate. When the hydrophobic fractions of T. hydatigena cyst fluid were
      employed as antigen in ELISA, no cross-reaction took place with sera from cattle
      infected with Fasciola hepatica, Ostertagia ostertagi, Cooperia oncophora,
      Dictyocaulus viviparus, Sarcocystis cruzi or a mixture of D. viviparus,
      Trichostrongylus axei and Eimeria. Using the Western blot technique, specific low
      molecular weight components (M(r) 10-18 kDa) of the hydrophobic fractions of the
      cyst fluid were reactive with sera from 14 of the 21 calves infected with T.
      saginata for 60 days. Also, hydrophobic fractions of T. hydatigena cyst fluid
      were dotted onto strips of filter membranes and reacted specifically with sera
      from 21 calves infected with T. saginata. This technique resulted in the highest
      sensitivity, detecting 17 of the 21 calves infected with T. saginata. Calves
      harbouring as few as 16, 26, 43, 53 and 74 cysts could be detected. Thirteen
      calves harbouring between 74 and 2,545 cysts were all detected. However, 4 calves
      harbouring 2, 22, 52 and 66 cysts, respectively, were not detected. The potential
      of using a dot blot technique in large scale investigations in the tropics is
      present. However, before accepting any of the three tests in the tropical
      environment, a broader spectrum of helminth infections should be evaluated for
      their eventual cross-reactivity.

PMID- 8541898
TI  - Managed care. Health care's main mantra migrates to the auto industry.

PMID- 8541897
TI  - Cultural diversity in the Hispanic market.

PMID- 8541899
TI  - Managing. Taking the measure of success.

PMID- 8541900
TI  - Mergers & acquisitions. Not-for-profits going for-profit.

PMID- 8541901
TI  - Finance. Money supply drying up for some hospitals.

PMID- 8541902
TI  - Ex-hospital CEOs. Where are they now?
AB  - One former hospital executive says his friends tell him he looks years younger.
      Another says he wanted to make more money, and now he can. And yet another says
      she wanted to start her own company before she was too old to enjoy it. These and
      other ex-CEOs left powerful positions, not to mention fancy corner offices, for
      an uncertain future. As it turns out, they're happier than ever. What do they
      know that you don't?

PMID- 8541903
TI  - A couple of headhunters sitting around talking. Discussion.
AB  - You can take advantage of your past to secure a more fulfilling future, though
      for most hospital CEOs it's not going to be easy. To do so requires hard work,
      dogged determination and a clear vision. Do you have what it takes to make the
      change and pull it off?

PMID- 8541904
TI  - Boom (and bust) in the physician management market.
AB  - Is it boom-time or bust for physician management companies? Their continued
      growth is at a critical juncture. Here are one expert's predictions for their
      future based on intuition, analysis and observation.

PMID- 8541905
TI  - My town, my hospital.
AB  - When our reporter read that his hometown hospital--Ottumwa Regional Health Center
      in Iowa--was on a list of the nation's hospitals most vulnerable to cuts in
      Medicare and Medicaid spending, he went to see why. What he found were executives
      coping with the future, not avoiding it. Here's what they did, how they did it-
      and why it might save them.

PMID- 8541906
TI  - Academic medicine. One hospital's managed care makeover.

PMID- 8541907
TI  - Catholic health care.

PMID- 8541909
TI  - Hospital pulse ... July 1995.

PMID- 8541908
TI  - Accounting. Getting patients to pay up.

PMID- 8541910
TI  - Health reform. Playing the game.

PMID- 8541911
TI  - Report cards. Giving consumers the scoop on quality and cost.

PMID- 8541912
TI  - Training. Military's med school still standing.

PMID- 8541913
TI  - Nursing. Is there life after acute care?

PMID- 8541914
TI  - Our fast-forward future.

PMID- 8541915
TI  - Quality watch. Shorter stays for New York patients.

PMID- 8541916
TI  - Physicians. What they expect to make.

PMID- 8541917
TI  - Managed care ... most recipients enrolled in Medicare HMOs are generally
      satisfied with their care.

PMID- 8541918
TI  - Employers ... Survey of Small and Mid-Sized Businesses.

PMID- 8541919
TI  - Pharmaceuticals ... should the U.S. Food and Drug Administration be remodeled.

PMID- 8541920
TI  - Anything but academic.
AB  - Even as academic medical centers accommodate themselves to the highly competitive
      -not to mention combative--world of managed health care, they're struggling to
      redefine their role before it gets redefined for them. "Academic institutions
      were never designed for managed care," one expert says. The question is, can they
      redesign themselves while there's still time?

PMID- 8541921
TI  - Who's going to suffer?

PMID- 8541922
TI  - John E. Abele. Interview by Karen Sandrick.

PMID- 8541923
TI  - Report card daze.
AB  - Doctors were angry when New York state began publishing the survival rates of
      cardiac surgeons' patients. But over time, those with less than stellar grades
      started to improve--if only to save their livelihoods. In the process, more
      patient lives have been saved. So why aren't other states doing the same?

PMID- 8541924
TI  - Emergency medicine. Are hospitals ready to respond?

PMID- 8541925
TI  - Hospital pulse ... August 1995.

PMID- 8541926
TI  - Politics. Hospital showdown lets voters decide.

PMID- 8541927
TI  - Reengineering. With an eye to the future.

PMID- 8541928
TI  - Role models. Painting physicians in a positive light.

PMID- 8541929
TI  - Executive chartbook. Who has too many beds?

PMID- 8541930
TI  - Unintended targets.

PMID- 8541931
TI  - In memoriam and memorial service Eli Robins, M.D. February 22, 1921-December 21,
      1994.

PMID- 8541932
TI  - Seasons and bipolar disorder.
AB  - The records of 377 bipolar disorder patients who were consecutively admitted to a
      general inpatient psychiatric unit in mid-Michigan over a 6-year period were
      examined. The seasonal variation of hospitalization, total sleep time, thyroid
      stimulating hormone, creatinine levels, lithium dosage and serum levels,
      aggressive behavior, and treatment outcome were analyzed. Among men, the
      admission rate peaked in the springtime. Women demonstrated a bimodal season
      distribution, with peak admission rates in spring and fall. Aggressive behavior
      in both men and women peaked in the spring (z = 2.50, p < 0.05). Men maintained
      on lithium achieved higher serum lithium levels during the summer months. These
      findings parallel previous reports regarding the influence of seasons upon
      bipolar disorder. The therapeutic implications related to seasonality and mania
      are discussed.

PMID- 8541934
TI  - Interrater and observer/self-report correlation of psychopathology in routine
      clinical practice.
AB  - Interrater (attending vs resident) and observer/patient self-report correlations
      were assessed for 17 and 9 symptom factors, respectively, in a consecutive sample
      of psychiatric outpatients at the time of intake evaluation in a university based
      clinic using the Hopkins Psychiatric Rating Scale (HPRS) and the SCL-90R. Highly
      significant interrater reliability was obtained for most items on the HPRS but
      observer/self-report correlations were more variable, ranging from good (r = .60
      to .75) for depression and phobic anxiety, to poor (r < .40) for obsessive
      compulsive, paranoia, and psychoticism symptoms. Results also varied by patient
      sex. The findings suggest a role for both observer and, for specific symptoms,
      self-report symptom scales in routine clinical practice.

PMID- 8541933
TI  - Substance use among schizophrenic outpatients: prevalence, course, and relation
      to functional status.
AB  - The prevalence and course of alcohol and drug use were examined in a
      longitudinal, retrospective study of 100 schizophrenic outpatients. During the 18
      month study period, problem substance use (abuse and dependence) was not
      associated with differential attrition from outpatient treatment. Thirty to forty
      percent of subjects were using drugs or alcohol during any evaluation period. The
      overall level of substance use and problem use of alcohol, marijuana, and other
      drugs remained stable, while problem use of cocaine and multiple substances
      increased over time. Problem substance use was associated with lower functional
      status and the detrimental effect of problem substance use appeared to increase
      with time. These findings underscore the need to address substance use problems
      in the context of outpatient schizophrenia treatment.

PMID- 8541935
TI  - Divalproex sodium as a treatment for borderline personality disorder.
AB  - Divalproex sodium was given to a series of individuals with the diagnosis of
      borderline personality disorder. Objective measures of agitation and anxiety were
      then used to assess the effect of divalproex sodium on such symptoms. Data were
      collected on the subjects and the amount of time spent in the agitated state was
      evaluated. We found that divalproex sodium reduced agitation in our subjects.

PMID- 8541936
TI  - Effect of pregnancy on three patients with bipolar disorder.
AB  - Case histories of three bipolar II disorder patients who had periods of sustained
      euthymia during all their pregnancies are described. The clinical and research
      implications of these observations are discussed.

PMID- 8541937
TI  - Management of asplenic patients in South Buckinghamshire: an audit of local
      practice.
AB  - People without spleens have an increased risk of pneumococcal and other
      infections. Immunisation is advised for this group of patients, but the role of
      prophylactic antibiotics remains unresolved. Since 1992, general practitioners in
      South Buckinghamshire have been encouraged to immunise all asplenic patients
      against infections with Streptococcus pneumoniae, Neisseria meningitidis, and
      Haemophilus influenzae type b (Hib). In addition, an 'alert' card, similar in
      principle to a medical warning bracelet, has been produced for general
      practitioners to issue to asplenic patients. General practitioners' clinical
      records of 293 asplenic patients were subsequently examined to evaluate this
      programme and assess the use of prophylactic antibiotics. Uptakes of 91%, 80%,
      and 79% were achieved for vaccines against pneumococcal, meningococcal, and Hib
      infections, respectively. Twenty-three per cent of patients had been advised
      immediately after splenectomy to take prophylactic antibiotics. Prophylaxis was
      advised for different periods of time, particularly in children. Thirty-four
      different antibiotic regimens had been recommended for adults. Clinical records
      suggested that 9% of patients were taking antibiotic prophylaxis at the time of
      the analysis. 'Alert' cards had been distributed to 88% of patients who were
      eligible. It is likely that most districts within the United Kingdom could set up
      similar immunisation and 'alert' card programmes. The wide variation in
      recommendations for antibiotic prophylaxis highlights the need for further
      research and the development of national guidelines.

PMID- 8541938
TI  - A school and community outbreak of influenza A.
AB  - In May 1995 a department of public health medicine was informed of an outbreak of
      respiratory and gastrointestinal illness in a local school. Eighty-three pupils
      and staff were affected out of a total of 247 people--an attack rate of 34%. The
      outbreak was investigated, control measures were instigated, and the outbreak
      subsided. Pupils and staff were surveyed and faecal specimens were collected.
      Blood specimens from a sample of pupils were examined serologically. No organisms
      were isolated from faecal specimens. Nine of the 18 blood specimens taken showed
      raised antibody titres against influenza A. This labour intensive investigation
      revealed a community outbreak of influenza A. Investigations in schools can be
      useful in community surveillance.

PMID- 8541939
TI  - Legionnaires' disease surveillance: England and Wales 1994.
AB  - One hundred and sixty cases of legionnaires' disease in England and Wales were
      reported to the PHLS Communicable Disease Surveillance Centre in 1994, a rate of
      3.1 cases per million population. Twenty-seven cases died. Eighty-nine cases
      (56%) were associated with travel, either in the United Kingdom (UK) or abroad,
      and six with a stay in hospital; the remaining cases were presumed to have
      acquired infection in the community. Seven outbreaks were detected in England and
      Wales: one was associated with a holiday centre, one with a hotel in London, two
      with industrial sites, and three occurred in the community. A further four
      clusters were associated with travel abroad: Spain, Ibiza, the Channel Islands,
      and a Mediterranean cruise. One hundred and twenty-eight of the 160 cases (79%)
      were sporadic--that is, not known to be associated with outbreaks--43 of which
      (34%) were not associated with travel nor acquired in hospital.

PMID- 8541940
TI  - 'Soundex' codes of surnames provide confidentiality and accuracy in a national
      HIV database.
AB  - Clinicians and microbiologists will participate in voluntary national reporting
      of HIV infections and AIDS only if they have confidence in the scheme's
      confidentiality. At the same time, if the data are to be accurate, it must be
      possible to recognise reports that refer to the same individual. The use of
      surname 'soundex' code in combination with date of birth meets both requirements.
      We describe its use in the database of reported HIV infections held at the PHLS
      AIDS Centre. By the end of 1994 over 93% of the 20,407 reports on the database
      were soundex coded, and 70% of AIDS reports were linked to independent reports of
      HIV infection from microbiologists. In 1994, 22% of the reports of HIV infection
      were recognised as duplicating earlier reports of infection. Coding surnames
      using soundex is an acceptable and practical tool in surveillance of an infection
      for which confidentiality is a prime concern.

PMID- 8541941
TI  - COVER/Korner 95-1 (April to June 1995). Vaccination coverage statistics for
      children up to 2 years old in the United Kingdom.

PMID- 8541942
TI  - Diphtheria in the New Independent States of the former Soviet Union.

PMID- 8541944
TI  - Diagnosis of meningococcal infections.

PMID- 8541943
TI  - The national measles and rubella campaign--one year on.

PMID- 8541945
TI  - Increased influenza activity in Great Britain.

PMID- 8541946
TI  - General pediatrics.

PMID- 8541947
TI  - Educating pediatric residents in community settings.
AB  - Pediatric training programs have recently witnessed a renewed emphasis on
      community-based experiences. This change can be attributed partly to the need for
      a more appropriate foundation for careers in general pediatrics and partly to a
      call for more generalist physicians as a result of health care reform. Community
      experiences provide optimal sites for residents to learn community-based primary
      care, practice management, collaboration with patient care teams, and advocacy on
      behalf of children's issues. The literature of the past year has focused on the
      theoretical issues, curricular components, and practical demands of implementing
      such experiences.

PMID- 8541948
TI  - Controversies of early discharge of infants from the well-newborn nursery.
AB  - A reduced hospital length of stay for normal newborns has become common, largely
      in an attempt to reduce hospital costs. Although evidence in the literature
      suggests that this is a safe practice, the overall quality of the studies is
      weak, and controversy exists regarding the advisability of this practice. A
      review of the rather modest literature and experience with shortened hospital
      stays lead us to conclude that early discharge of newborns is safe if it is but
      one component of a larger program designed to transfer portions of care
      traditionally provided in the hospital to pre- and postnatal care provided
      outside the hospital. The early discharge program developed at the Harvard
      Community Health Plan is presented as an example of such a program, with the hope
      that this model will provide a useful framework to those who are involved with
      shortened hospital maternity lengths of stay.

PMID- 8541949
TI  - Primary care of children with HIV infection.
AB  - As the number of children affected by the HIV epidemic increases, the primary
      care physician can have an important role in ensuring that these children receive
      comprehensive health care. Clinical aspects of pediatric HIV disease are
      reviewed, including the recently revised Centers for Disease Control and
      Prevention classification system. Important advances include the development and
      application of techniques for establishing in early infancy whether or not a
      child is infected. The implications for the use of these techniques are
      discussed, and recommendations are made for a system of coordinated care between
      the primary care physician and specialty clinic. Specific treatment approaches,
      such as the early introduction of Pneumocystis carinii pneumonia prophylaxis,
      antiretroviral medications, and the use of intravenous immunoglobulin, are
      discussed.

PMID- 8541950
TI  - Management of acute and chronic otitis media in pediatric practice.
AB  - This article reviews recent publications related to the epidemiology,
      pathogenesis, diagnosis, and management of otitis media. Otitis media is a
      continuum of conditions that includes acute otitis media, otitis media with
      residual or persistent effusion, unresponsive otitis media, recurrent otitis
      media, otitis media with complications, and chronic suppurative otitis media. The
      pathogenic mechanisms of otitis media involve interactions among host
      characteristics, virulence factors of viral and bacterial pathogens, and
      environmental factors. Recent studies document the emergence and rapid spread of
      drug-resistant Streptococcus pneumoniae in acute and unresponsive otitis as well
      as persistent effusions and chronic suppurative otitis. Few issues in clinical
      medicine are as controversial as the efficacy and risks associated with
      antibiotic treatment of otitis media. It is best to avoid the antibiotic
      treatment dilemma as much as possible by not overdiagnosing otitis media.

PMID- 8541951
TI  - Updates in pediatric emergency medicine for the office practitioner.
AB  - Emergently ill or injured children may access care through their primary care
      provider, through prehospital emergency medical services, or directly in a
      hospital emergency unit. Primary health care providers and emergency care
      providers need to have the skills, proper equipment, and medications available to
      care for these children. This paper reviews recent articles on the prevention,
      evaluation, treatment, and outcomes of illness and injury in children, which
      should be of interest to primary and emergency care givers. Areas of recent
      research include the epidemiology, prevention, and evaluation of childhood
      injuries and the evaluation of infants and children with fever. Other areas
      reviewed are respiratory disease and the treatment of gastroenteritis. Also
      reviewed are articles on the role of the primary care physician in emergency
      medical services for children.

PMID- 8541952
TI  - Recurrent abdominal pain in children.

PMID- 8541953
TI  - Portal hypertension in children.
AB  - Portal hypertension is an uncommon but serious complication in children. The
      etiology may be intrahepatic or from an extrahepatic vascular occlusion. The
      pathophysiology is unknown, but the development of increased vascular resistance
      and portal flow are believed to be the primary changes. Increased portal flow is
      created by a decrease in systemic vascular resistance regionalized to the
      splanchnic vascular bed. Abnormally reduced response to vasoactive substances may
      be responsible. Advances in ultrasonography and endoscopy may improve our ability
      to evaluate portal hypertensive vascular changes. However, pharmacologic
      management is still limited to controlling the hemodynamic disturbances after
      they have occurred. Nonsurgical shunt management is increasingly being used in
      children, limiting the need for surgical shunt placement. Liver transplantation
      is now a viable option for managing end-stage disease. Future management depends
      on understanding the role of vasoactive substances controlling portal flow
      velocity, subsequent development of targeted pharmacologic therapy, and
      application of nonsurgical shunt technology in children. Transjugular
      intrahepatic portosystemic shunt placement is the next technologic advance moving
      from the adult into the pediatric realm.

PMID- 8541954
TI  - Chronic hepatitis in children.
AB  - Autoimmune hepatitis is an inflammatory disease of the liver of unknown etiology
      that progresses toward cirrhosis and liver failure and is generally responsive to
      immunosuppressive treatment. The presence of anti-smooth muscle antibodies with
      anti-actin specificity and of anti-liver kidney microsomal antibodies defines two
      distinct subgroups of the disease. An autoantibody against liver cytosolic
      antigens has recently been described. Management of autoimmune hepatitis relies
      on immunosuppressive therapy with steroids alone or combined with azathioprine.
      When the disease is poorly controlled, despite good patient compliance to
      therapy, cyclosporin should be recommended. Progressive liver disease in chronic
      hepatitis B in adults has been associated with the presence of precore mutants of
      hepatitis B virus. In children, the presence of precore mutants seems not to
      affect the rate of seroconversion to anti-hepatitis B e antigen. However, high
      viremic levels of precore mutants are associated with persistent viral
      replication and liver disease. Interferon alfa seems to be less effective in
      children than in adults in the treatment of chronic hepatitis B; however, it
      hastens the seroconversion rate to anti-hepatitis B e antigen, accelerating the
      spontaneous clearance of the virus in children with already low levels of viral
      replication. Blood transfusions, especially those received in the perinatal
      period, are the single most important source of infection with hepatitis C in
      childhood. HIV coinfection is a major risk factor for vertical transmission of
      hepatitis C virus in pregnant women. Chronic hepatitis C in children is usually
      an asymptomatic disease associated with mild to moderate fluctuation of
      aminotransferase activities and histologic features of mildly active hepatitis.
      Severe active hepatitis and cirrhosis are infrequent during childhood and
      adolescence. Interferon may have a place in the treatment of chronic hepatitis C
      in children.

PMID- 8541955
TI  - Inflammatory bowel disease in children.
AB  - Inflammatory bowel disease remains a serious chronic illness in children. Recent
      developments in the care of these patients involves both basic science research
      into the pathophysiology of ulcerative colitis and Crohn's disease and the
      development of refinements in the surgical techniques and medical therapies
      available as treatment options. In Crohn's disease, a new steroid analogue
      (budesonide) shows some promise as a possible medical treatment that would limit
      the devastating side effects of steroids in children. In addition, the bowel
      sparing technique of strictureplasty has now been reported in children with good
      results. In ulcerative colitis, the surgical technique of endorectal pull-through
      continues to evolve with reports of the efficacy of specific pouch designs and
      surgical techniques. An understanding of pouchitis, the most common complication
      of endorectal pull-through, has focused on documenting specific alterations in
      the microbiology and physiology of the pouch, as well as investigating a possible
      link between autoantibodies and susceptibility to this complication.

PMID- 8541956
TI  - Helicobacter pylori infection and peptic ulcer disease in children.
AB  - Peptic ulcer disease is an uncommon disorder in children. The recent upsurge of
      interest in peptic ulcer disease in children can be attributed to the importance
      of studies of children in establishing the role of Helicobacter pylori in the
      pathogenesis of ulcer disease. This review of recent publications focuses on the
      role of the organism in peptic ulcer disease, the epidemiology of H. pylori, its
      significance as a cause of symptoms, and recent advances in the treatment of this
      infection. The increasing evidence that chronic H. pylori gastritis is possibly a
      significant risk factor for the development of gastric carcinoma is also
      discussed.

PMID- 8541957
TI  - Short bowel syndrome in children.
AB  - Short bowel syndrome is defined as malabsorption following small intestinal
      resection. There are many causes in children, most of whom present during
      infancy. The clinical presentation and physiologic consequences depend heavily on
      the segment of bowel removed and the extent of resection. The remaining intestine
      has the capacity to adapt anatomically and functionally, and stimulating the
      adaptation process is a major component of therapy. Clinical management of long
      term complications, such as bacterial overgrowth, nutrient deficiency states, and
      parenteral nutrition-induced liver disease, are often key outcome determinants.
      The recent availability of intestinal transplantation now provides an additional
      therapeutic option for patients in whom all other forms of therapy fail.

PMID- 8541958
TI  - Cardiovascular medicine.

PMID- 8541959
TI  - Advances in surgical care of infants and children with congenital heart disease.
AB  - Recent important technical developments in the field of surgery for congenital
      heart disease have included the Ross pulmonary autograft replacement of the
      aortic valve, video-assisted thoracoscopic surgery, and the double-switch and
      switch-Rastelli procedure for congenitally corrected transposition. Although the
      growth potential of the pulmonary autograft has been confirmed, an important
      incidence of late aortic regurgitation has been noted. Expanding indications for
      video-assisted thoracoscopic surgery have been described, including division of
      the vascular ring. Late hemodynamic assessment after the double-switch or switch
      Rastelli procedure will encourage increased application of this repair. Both
      clinical and laboratory studies have focused on neurologic and developmental
      outcome after cardiac surgery. Perioperative seizures in young infants have been
      found to be associated with impaired psychomotor development at 1 year of age. In
      the area of perioperative management, the antifibrinolytic agents tranexamic
      acid, epsilon-aminocaproic acid, and aprotinin have been found to be useful in
      reducing postoperative hemorrhage. Nitric oxide is useful in reducing
      postoperative pulmonary hypertension. Late clinical follow-up studies of patients
      with single ventricle have revealed an important incidence of pulmonary
      arteriovenous malformations after a bidirectional Glenn shunt and atrial flutter
      after a Fontan procedure. Late assessment of patients after the arterial switch
      procedure for transposition has revealed preservation of ventricular function and
      an extremely low incidence of late arrhythmias.

PMID- 8541960
TI  - Advances in cardiac imaging in congenital heart disease.
AB  - Miniaturization of echocardiographic transducers, improved crystal technology,
      and enhanced digital processing of ultrasound signals have resulted in newer,
      more sophisticated equipment and imaging techniques. These technologic advances
      include transesophageal echocardiography, stress echocardiography (both
      pharmacologic and exercise), intravascular and intracardiac ultrasound, and three
      dimensional echocardiography. Magnetic resonance imaging is also becoming
      increasingly important in the visualization of specific pathologies. These
      advances in cardiac imaging are discussed, with prime emphasis placed on present
      and future clinical applications in congenital heart disease.

PMID- 8541961
TI  - Recent advances in the etiology, diagnosis, and treatment of myocarditis and
      cardiomyopathies in children.
AB  - The cardiomyopathies are usually classified as dilated, hypertrophic, or
      restrictive. Although clinical presentations vary among these myopathies,
      systolic or diastolic dysfunction characterizes the principal pathophysiologic
      features of each. Advances in genetic linkage analysis and mutation screening
      have recently allowed investigators to establish a genetic basis for several
      forms of dilated and hypertrophic cardiomyopathy. Although traditional treatment
      modalities and newer strategies (such as atrioventricular pacing in patients with
      dilated cardiomyopathy and pacing or amiodarone therapy for patients with
      hypertrophic cardiomyopathy) may provide short-term relief, cardiac
      transplantation may be the only intervention that can alter the natural history
      and poor prognosis for these potentially lethal conditions. Myocarditis, which
      usually presents as an acute form of dilated cardiomyopathy, may have a broad
      spectrum of presentation and is currently treated with nonspecific supportive
      measures. Although the polymerase chain reaction may provide rapid diagnosis of
      viral etiologies, newer therapies have not yet been developed. Clinical trials
      with intravenous immunoglobulin, however, are currently in progress. In patients
      whose symptoms do not resolve, cardiac transplantation may afford the only
      potential for long-term survival.

PMID- 8541962
TI  - Evaluation and recommendations for participation in athletics for children with
      heart disease.
AB  - Physical fitness is becoming increasingly emphasized in our society. Everyone is
      encouraged to participate in routine exercise, and many desire to compete in
      organized athletics. Patients with heart disease are living longer, healthier
      lives and may also desire sports participation. Because selected patients may be
      at risk for sudden death, a thorough evaluation should be performed. The purpose
      of this article is to familiarize the reader with basic principles of exercise
      physiology and preparticipation evaluation and to provide a guideline to
      recommending athletic involvement in patients with heart disease.

PMID- 8541963
TI  - Standardizing care delivery for infants and children with common congenital
      cardiac lesions.
AB  - The emergence of managed care is influencing the practices of pediatric
      cardiology and cardiac surgery. The need for efficiencies brought about by
      standardizing care whenever possible has led to the development of care
      guidelines and clinical pathways. Care guidelines are general algorithms mapping
      the care of a specific problem. They are patient oriented and cover all aspects
      of care from diagnosis onward. National task forces have recently published
      guidelines for the care of children with specific congenital cardiac defects, and
      some of these are reviewed. Clinical pathways are more specific to an episode of
      inpatient or outpatient care. They consist of expected defined outcomes of care,
      including all tests, monitoring, and intervention. In other fields, clinical
      pathways have been developed for specific diagnoses or procedures. However, in
      pediatric cardiac surgery, the variety of conditions and operations is so great
      that two different methods of acuity-based, rather than disease-based, clinical
      pathway methodologies were developed that have been shown to decrease lengths of
      stay and hospital charges. Refinement of the system will require more
      sophisticated data, including the delineation of actual costs rather than
      charges, along with refinement and standardization of outcomes measurements. With
      fundamental changes in the delivery system, the roles of the specialist and the
      primary care physician have undergone changes that will continue to evolve.
      Vigilance on the part of all providers will be necessary to assure quality of
      care in this new milieu.

PMID- 8541964
TI  - An 8-week-old girl with wheezing and respiratory distress.

PMID- 8541965
TI  - Atopic disease, rhinitis and conjunctivitis, and upper respiratory infections.
AB  - In this section, we review three broad topics in pediatrics: atopic disease,
      rhinitis and conjunctivitis, and upper respiratory tract infections. These topics
      comprise three of the most commonly encountered problems in pediatric practice.
      There have been significant contributions to the pediatric literature in each of
      these areas over the past year, and we review those of particular interest here.
      The papers that we have chosen to review were selected for both their scientific
      significance and practicality. Both review articles and original research are
      included, but all should be relevant to the care of your patients.

PMID- 8541966
TI  - G. Paul Moore Lecture. Rational thought: the impact of voice science upon voice
      care.
AB  - Recent evolution in scientific knowledge and technology has led to monumental
      improvement in the standard of care for patients with voice disorders. New
      concepts in anatomy, physiology, measurement, and analysis have provided voice
      care professionals with not merely better understanding, but moreover an
      extensive vocabulary with which to think about voice function and dysfunction.
      Previously, we had to depend too much upon anecdote and "the art of medicine."
      Thanks to scientific advances, we now have the tools we need for rational thought
      about the human voice. This is the fundamental change responsible for recent
      great advances in voice care.

PMID- 8541967
TI  - Expression of emotion in voice and music.
AB  - Vocal communication of emotion is biologically adaptive for socially living
      species and has therefore evolved in a phylogenetically continuous manner. Human
      affect bursts or interjections can be considered close parallels to animal affect
      vocalizations. The development of speech, unique to the human species, has relied
      on the voice as a carrier signal, and thus emotion effects on the voice become
      audible during speech. This article reviews (a) the evidence on listeners'
      ability to accurately identify a speaker's emotion from voice cues alone, (b) the
      research efforts trying to isolate the acoustic features that determine listener
      judgments, and (c) the findings on actual acoustic concomitants of a speaker's
      emotional state (real or portrayed by actors). Finally, based on speculations
      about the joint origin of speech and vocal music in nonlinguistic affect
      vocalizations, similarities of emotion expression in speech and music are
      discussed.

PMID- 8541968
TI  - Acoustic concomitants of emotional expression in operatic singing: the case of
      Lucia in Ardi gli incensi.
AB  - Two excerpts from the cadenza in Ardi gli incensi from Donizetti's opera Lucia di
      Lammermoor were acoustically analyzed for five recorded versions of the cadenza
      by Toti dal Monte, Maria Callas, Renata Scotto, Joan Sutherland, and Edita
      Gruberova. These acoustic parameters of the singing voices were correlated with
      preference and emotional expression judgments, based on pairwise comparisons,
      made by a group of experienced listener-judges. In addition to showing major
      differences in the voice quality of the five "dive" studied, the acoustic
      parameters suggested which vocal cues affect listener judgments. Two component
      scores, based on a factorial-dimensional analysis of the acoustic parameters,
      predicted 84% of the variance in the preference ratings.

PMID- 8541969
TI  - Congruence in personality between clinician and client: relationship to ratings
      of voice treatment.
AB  - This study examined relationships between ratings of voice therapy sessions and
      clinician and client personality characteristics as measured by the Myers-Briggs
      Type Indicator. Nineteen clinician-client pairs were rated on behaviors
      demonstrated in two therapy sessions. Results indicated that client variables of
      thinking-feeling and judgment-perception were related to amount of clinician
      feedback, client eye contact, ratio of clinician-client eye contact and amount of
      clinician explanation, clarity of explanation, clinician's initiative, and client
      eye contact, respectively. Clinicians' sensing-intuition was related to the
      amount of feedback to client and quality of the task sequence. Clinician's
      judgment-perception was related to amount of explanation and client's attention
      to clinician. Similarity in clinician-client sensing-intuition was related with
      task involvement of the client, clinician's attention to client, and clinician
      eye contact. Similarity in judgment-perception was related to greater use of
      counseling. Similarity in thinking-feeling was related to low amounts of
      clinician eye contact.

PMID- 8541970
TI  - Psychogenic spasmodic dysphonia: a case study with expert opinions.
AB  - Spasmodic (spastic) dysphonia (SD) is considered by some to be a neurologic
      syndrome and by others a symptom complex of multiple etiologies, neurologic and
      psychogenic. A case of a 26-year-old female psychiatric nurse with psychogenic SD
      (PSD) is presented. The dysphonia was alleviated within one session of voice
      therapy. Psychogenic etiology was established by the author, based on three
      diagnostic criteria--symptom incongruity, symptom reversibility, and symptom
      psychogenicity. Seven nationally recognized voice experts listened to audio
      recorded samples of the patient's pre- and posttherapy voice during
      conversational speech. The experts agreed that the dysphonia was psychogenic and
      characterized it as staccato-like speech, effortful phonation, and interrupted
      flow of speech; six characterized it with intermittent voice arrests (voice
      stoppages); five with hoarse-harsh voice; and four with waxing and waning,
      strained-strangled phonation. These are often described as salient features of
      SD. Nevertheless, the experts disagreed among themselves as to whether the
      dysphonia was characteristic of SD and should be labeled as such. The author
      argues that as long as the voice characteristics and pathophysiologic findings
      that constitute SD are not well delineated, and as long as the diagnosis of SD is
      based on symptoms alone, patients with psychogenic or poorly understood voice
      disorders are likely to be misdiagnosed with organic (neurologic) SD and thus
      subjected to undue medical treatment. The author also argues that the debate over
      the etiology of SD can be resolved if SD is considered a neurologic syndrome, PSD
      a nonorganic phonatory disorder that mimics the syndrome, and if the voice
      symptoms and pathophysiologic characteristics of SD are well defined and agreed
      on.

PMID- 8541971
TI  - Patterns of fundamental frequency for three types of voice samples.
AB  - The purpose of this study was to determine the variability in speaking
      fundamental frequency (Fo) associated with sample type in two age groups of
      normal male and female speakers and a group with vocal-fold paralysis. Young and
      elderly normal control men and women produced a sustained vowel, read a passage,
      and spoke extemporaneously in the morning, early afternoon, and late afternoon on
      three different days. The vocal-fold-paralysis group produced two voice samples
      at different times on the same day. Two patterns of variability emerged in the
      normal groups. Young men produced sustained phonation at a significantly lower Fo
      than their reading or extemporaneous samples. Young and older women and older men
      produced sustained phonation with a higher Fo than their reading or
      extemporaneous samples. The eight subjects with unilateral vocal-fold paralysis
      (seven women, one man) produced samples with a pattern similar to that of the
      older normal groups but with greater differences between the sustained vowel and
      speech samples. The use of different sample types resulted in variations in mean
      speaking Fo in the normal subjects as well as in the vocal-fold-paralysis group.
      Within-day sampling of all normal subjects resulted in approximately the same
      variability as across-day sampling. In the vocal-fold-paralysis group, within-day
      sampling resulted in greater variability of mean Fo for vowels than for connected
      speech, following a pattern similar to the older normal control subjects and
      various speech materials for voice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8541972
TI  - Measurement of formant frequencies and bandwidths in singing.
AB  - That singers under certain circumstances adjust the articulation of the vocal
      tract (formant tuning) to enhance acoustic output is both apparent from
      measurements and understood in theory. The precise effect of a formant on an
      approaching (retreating) harmonic as the latter varies in frequency during actual
      singing, however, is difficult to isolate. In this study variations in amplitude
      of radiated sound components as well as supraglottal and subglottal (esophageal)
      pressures accompanying the vibrato-related sweep of voice harmonics were used as
      a basis for estimating the effective center frequencies and bandwidths of the
      first and second formants.

PMID- 8541973
TI  - Sentence/vowel correlation in the evaluation of dysphonia.
AB  - Considering the widespread use of the sustained vowel in the evaluation of voice
      disorders, our objective was to study the degree to which the vowel is
      representative of voice in continuous speech. Phonatory samples were recorded
      from 20 normal subjects and 60 patients representing commonly occurring voice
      problems (nodules, unilateral paralysis, and functional). The phonatory samples
      were evaluated by 25 listeners on the basis of 12 bipolar, semantic differential
      scales. Factor analysis produced two perceptual dimensions with similar loadings
      for both vowels and sentences. A correlation of 0.78 was obtained between vowels
      and sentences on factor 1 scores, "vocal severity," and a correlation of 0.77 was
      obtained between vowels and sentences on factor 2 scores, "pitch/quality." Six of
      the 80 pairs of sentences and vowels differed by two scale points or more on
      vocal severity. Results suggest that although a relatively strong relationship
      exists between the two measures, sustained vowel sounds may not be an adequate
      clinical index to the dysphonic severity of continuous speech.

PMID- 8541974
TI  - Voice profiles and standard voice profile of untrained children.
AB  - Voice profiles were taken of 277 healthy children between the ages of 5 and 14
      years. The measured phonetograms were grouped according to sex and years of age.
      In each group, the means and standard deviations of maximal and minimal volume of
      each frequency were calculated. The median was used to establish the upper and
      lower limits of the voice range of each group. No age-dependent changes of the
      group voice profiles were shown in the groups of 7 to 10 year olds. Out of that
      emerged a standard childhood voice profile of the untrained voice. After age 10,
      an increase of the dynamic range over the lowest frequencies was found. Because
      of the voice changes in puberty, a profile for 13- and 14-year-old boys could not
      be established.

PMID- 8541975
TI  - Alternative medicine: does it play a role in the management of voice disorders?
AB  - Alternative medicine has begun to receive the attention of the legitimate medical
      community. Recent evidence reveals that 34% of American adults interviewed
      reported using at least one unconventional therapy during 1994. A 3-month survey
      of patient inquiries, conducted at The Voice Center, Beth Israel Hospital,
      Boston, MA, U.S.A. revealed that 41% of patients made inquiries about the
      potential use of "unconventional approaches" in the management of their voice
      disorders. Alternative medicine, while largely unproven for efficacy, represents
      a rapidly growing approach. The present article defines several alternative
      medical practices, describes their theories and potential impact on the
      management of voice disorders, and calls for empirical studies to follow. The
      alternative practices discussed are limited to behavioral therapies such as
      massage therapy, creative visualization, Alexander, mindfulness, and mediatation.

PMID- 8541976
TI  - Stroboscopic signs associated with benign lesions of the vocal folds.
AB  - Stroboscopic signs were systematically rated for a group of 80 patients with
      benign vocal fold lesions, most of whom had either a nodule or a polyp. Each
      group revealed a characteristic pattern of ranking of signs and exhibited
      differences of most predominant signs. The results of the ratings were submitted
      to a multiple discriminant analysis to determine if post hoc stroboscopic ratings
      could be used to correctly classify patients into one of four diagnostic groups
      and into one of two treatment groups. All patients except one were correctly
      classified into the diagnostic groups, and all were correctly classified into the
      treatment groups. The important signs for classifying patients into the
      diagnostic groups were roughness of the edge of the affected vocal fold, phase
      closure pattern, and phase symmetry. The important signs for classifying patients
      into the treatment groups were roughness of the edge of the affected vocal fold,
      glottal closure configuration, and vibration characteristics of the affected (or
      more affected) vocal fold. The results suggest that objective evaluation of
      stroboscopic examinations can be valuable in correctly diagnosing patients and in
      selecting the proper treatment regimen for the patient.

PMID- 8541977
TI  - Vocal nodules, microwebs, and surgery.
AB  - Successful treatment of vocal nodules is primarily accomplished through the
      direction of voice-language pathologists and teachers of music and speech. Rarely
      is surgical treatment necessary, although recent reports have suggested a
      correlation between vocal nodules and failed voice training with anterior
      commissure microwebs. One hundred fifteen consecutive patients with vocal nodules
      were evaluated. Eight anterior commissure microwebs were identified (7%), four of
      these in performers. Of the 96 patients with sufficient follow-up, 65 (68%) had
      complete resolution of their nodules and 17 (18%) had sufficient improvement to
      return to normal vocalization without surgical treatment. Nine patients required
      surgery, two of these with anterior commissure microwebs. All eight patients with
      microwebs had resolution of their nodules with either nonsurgical or surgical
      therapy. In total, 94% of patients were able to return to normal voice function,
      while the 6% of failures either did not receive or were noncompliant with voice
      therapy. Microwebs were found to be uncommon in patients with vocal nodules.
      Microwebs and other laryngeal pathologies in patients with nodules may be
      associated with a higher incidence of patients failing conservative voice therapy
      treatment.

PMID- 8541978
TI  - Endoscopic microsuture repair of vocal fold defects.
AB  - The presence of a nonvibratory segment of vocal folds after microlaryngeal
      surgery is often a cause of poor voice result. The etiology of a nonvibratory
      segment is due to full thickness epithelial defect followed by secondary wound
      closure and scar contracture. To reduce scar contracture and nonvibratory segment
      of the vocal folds, primary repair with a 6-0 chromic endo-knot suture technique
      was used to close defects and approximate microflaps of the vocal folds. This was
      done in 18 patients with epithelial defects after resection of benign vocal fold
      lesions. The pathologic findings included severe polypoid degeneration (n = 7),
      fusiform laryngeal polyps (n = 5), sulcus vocalis (n = 2), cyst (n = 2), and
      keratosis (n = 2). Voice was improved in all patients after surgery. Comparison
      of vocal fold vibration before and after surgery showed improvements in
      configuration, amplitude, and mucosal wave. Vocal folds that were sutured all had
      good vibratory characteristics; none had a nonvibrating segment at the site of
      suture placement. Voice and healing after microsuture technique were near normal
      by Day 10 and return of mucosal wave was often complete by Day 14. Endoscopic
      microsuture closure of microflaps of the vocal folds edge is safe and affords the
      surgeon an opportunity for primary repair with improved functional result.

PMID- 8541979
TI  - Future of biotechnology-based control of disease in marine invertebrates.
AB  - Infectious disease is the single most devastating problem in mollusc and shrimp
      aquaculture. Pathogens causing the greatest problems have been identified as
      viruses, prokaryotes, and protozoans. Two approaches employing methods of
      biotechnology have been proposed to prevent, manage, and control mollusc and
      shrimp diseases. The first is development of a diagnostic scheme for detection
      and identification of pathogens, using molecular probes. This offers the
      opportunity for prophylactic measures to be taken. Molecular probes have been
      prepared for the major pathogens of molluscs, but in the case of shrimp
      pathogens, only a few are available. Monoclonal antibodies have also been
      prepared and are used in immunodiagnosis, e.g., immunofluorescence detection.
      Such diagnostic tools are relatively new to aquaculture, but have enormous
      potential. A second approach to the control of disease in marine invertebrates,
      notably shrimp, involves use of genetically transformed strains resistant to
      specific pathogens. Pathogen-resistant transgenic animals have been developed,
      but such research has only just begun for molluscs and shrimp. Transfection
      methods applied to mollusc and shrimp embryos have been successful, with
      preliminary data showing efficiency of heterologous promoters in controlling
      expression of reporter genes. Other transformation systems also show promise,
      including transposable elements and densoviruses.

PMID- 8541980
TI  - The cDNA sequence of the lactate dehydrogenase-A of the spiny dogfish (Squalus
      acanthias): corrections to the amino acid sequence and an analysis of the
      phylogeny of vertebrate lactate dehydrogenases.
AB  - The cDNA sequence of the lactate dehydrogenase-A (LDH-A) of the spiny dogfish was
      determined. The deduced amino acid sequence differed from a previously determined
      protein sequence by 5%. Separate maximum parsimony analyses of the two sequences
      along with LDHs of other vertebrates resulted in shorter trees with the sequence
      presented here, as well as fewer equally parsimonious trees. The new sequence
      also indicates a greater conservation of length among vertebrate LDHs than was
      previously suspected. Analyses of the phylogeny of vertebrate LDHs resulted in a
      monophyletic grouping of LDH-As, from within which mammalian LDH-C is derived.
      The phylogeny of LDH-As did not exactly match the phylogeny of the organisms,
      raising the possibility of multiple origins and losses of a muscle-predominant
      gene. LDH-Bs appear to have shared a single origin.

PMID- 8541981
TI  - Purification and characterization of two pancreatic elastase isoforms from
      dogfish (Scyliorhinus canicula).
AB  - Two elastase isoforms were isolated from activated pancreatic extract of dogfish
      (Scyliorhinus canicula). The purification procedures for both elastases included
      ammonium sulfate fractionation, ion exchange on DEAE cellulose and Mono-QHR
      column followed by gel filtration on PL-GFS (HPLC) column. The two isoenzymes, EI
      and EII, exhibit a high activity toward the specific elastase substrate succinyl
      (ala)3-p-nitroanilide (SANA) with different kinetic parameters at 37 degrees C.
      However, the two different enzymes have similar properties on the basis of pH,
      temperature, and molecular weight study. The activity of both variants was
      completely inhibited by elastatinal, phenylmethyl sulfonyl fluoride, (PMSF),
      diisopropyl fluorophosphate, (iPr2-FP), but less by p-chloromercuribenzoic acid
      (PCMB) and soybean trypsin inhibitor. EI and EII have similar amino acid
      composition; their amino-terminal sequences have 85% homology with human and rat
      elastase 2.

PMID- 8541982
TI  - Wresting the muscle from mussel beards: research and applications.
AB  - Marine and zebra mussels secrete byssal beards to attach themselves
      opportunistically to hard surfaces in their environment. By doing this, they
      naturally earn a reputation as fouling pests. The protein precursors of byssus in
      mussels are being investigated in the hope not only of discovering specific
      measures against these marine foulers, but also to gain some insights into the
      technically challenging task of engineering adhesive bonds underwater. Although
      byssal proteins are all part of the bearded glue that bonds them to a surface,
      they can be subdivided into three types depending on the function that they serve
      in byssal threads: (1) fibrous proteins form the load-bearing cables in the core
      of the threads, (2) cuticular proteins form a protective coat around the cables,
      and (3) adhesive proteins connect the cables to a foreign surface. A flaw in any
      one of these will undermine a mussel's ability to attach. The fibrous proteins
      can be collagenous, silk-like, elastic, or any combination of these. Covering
      these are the cuticular proteins, which are distinguished by their surface
      coupling properties, tandemly repeated primary sequence, and their high content
      of lysine and the exotic amino acid 3,4-dihydroxyphenyl-L-alanine (DOPA). The
      adhesive proteins are of low molecular weight, contain DOPA, and assemble to form
      microcellular solids (foams). Several of these proteins are already attracting
      biotechnological attention as cell and tissue attachment factors, anticorrosives,
      and metal-sequestering reagents.

PMID- 8541983
TI  - Use of aquatic organisms as models to determine the in vivo contribution of
      flavin-containing monooxygenases in xenobiotic biotransformation.
AB  - In an attempt to understand the evolution and role of flavin-containing
      monooxygenases (FMOs) in xenobiotic biotransformation by aquatic organisms, a
      survey of hepatic FMO activity (N,N-dimethylaniline N-oxidase and thiourea
      oxidase) was performed in one brackish water fish and 17 species of freshwater
      fish, one of which was anadromous. Only hepatic microsomes from the brackish
      water medaka (Oryzia latipes), the freshwater centrarid Lepomis macrochirus, and
      the anadromous rainbow trout (Oncorhynchus mykiss) consistently demonstrated FMO
      activity. Previous studies in trout have shown that the carbarmate insecticide,
      aldicarb, is bioactivated through an FMO-catalyzed S-oxidation. The toxicity of
      aldicarb was examined in O. mykiss and one of the species that did not show
      measurable FMO activity or protein, the channel catfish (Ictalurus punctatus).
      Rainbow trout were approximately 100 times more sensitive to aldicarb toxicity
      compared with channel catfish after a 96-hour waterborne exposure or 24 hours
      following intraperitoneal injection. However, rainbow trout were only 10 times
      more sensitive to aldicarb S-oxide, the bioactivated metabolite, than catfish 24
      hours following intraperitoneal injection. Elimination profiles of injected
      aldicarb in both species fit a two-compartment model, but half-lives were
      significantly different between each species. Aldicarb and metabolites were
      rapidly cleared from trout (respective alpha and beta half-lives being 3 and 28
      hr), while half-lives in catfish were significantly longer (alpha and beta half
      lives being 16 and 140 hr). The major metabolite from catfish after 24 hours was
      aldicarb sulfone, which was 9.3% of the total dose. In trout, aldicarb sulfoxide
      was the major metabolite (7.6% of total dose) without any measurable sulfone.
      Because cytochrome P450 monooxygenases also perform the S-oxidation of aldicarb
      and differences in aldicarb disposition exist, future experiments will attempt to
      transfect catfish with rainbow trout FMO cDNA in order to determine the role of
      FMOs in aldicarb biotransformation and toxicity.

PMID- 8541985
TI  - Rapid detection of Vibrio cholerae contamination of seafood by polymerase chain
      reaction.
AB  - The possibility of detecting Vibrio cholerae contamination of seafood using a
      technique based on polymerase chain reaction (PCR) was studied. Direct PCR on
      lysate prepared from fish homogenates containing 10(3) V. cholerae/ml gave a
      positive reaction. When combined with alkaline peptone water (APW) enrichment,
      homogenates containing 1.4 cells/ml gave amplification signal. The technique
      could also detect V. cholerae O139, the recent epidemic serotype in the Indian
      subcontinent. An environmental isolate of non-O1 V. cholerae that produced
      cholera toxin was also positive in this assay. The results suggest that PCR-based
      techniques have great potential in quick detection of toxigenic V. cholerae in
      seafoods.

PMID- 8541984
TI  - Rhamnolipid biosurfactant enhancement of hexadecane biodegradation by Pseudomonas
      aeruginosa.
AB  - Mutants of Pseudomonas aeruginosa that produce and do not produce rhamnolipid
      biosurfactant are used to investigate the influence of cell-associated
      biosurfactant on cellular association with the hydrocarbon-water interface and on
      hydrocarbon uptake. Rhamnolipid-nonproducing mutant 65E12 of P. aeruginosa is
      unable to grow in minimal media containing hexadecane as a carbon source in the
      absence of exogenously added surfactant. Mutant PG201::rhlR grows very slowly in
      the absence of exogenously added surfactants. Both mutants are deficient in the
      positive regulatory gene controlling the activation of rhamnolipid synthesis.
      65E12 is a double mutant that is also deficient in lipopolysaccharide synthesis.
      However, growth on hexadecane may be restored to varying degrees when small
      amounts of purified rhamnolipids or the synthetic anionic surfactant alkyl
      benzene sulfonate (ABS) is added to the cultures. Rhamnolipid biosurfactant is
      shown to be approximately 9 times more effective than the structurally similar
      synthetic anionic surfactant ABS in solubilizing hydrocarbon into the aqueous
      phase. Physical characteristics of the rhamnolipid and ABS micelles as determined
      by laser light scattering are described to explain the greater effectiveness of
      the rhamnolipid in solubilizing hexadecane. The cellular attachment to
      hydrocarbon-water interfaces and cellular aggregation of the wild-type and mutant
      strains are examined in the presence and absence of rhamnolipid or synthetic ABS
      surfactants. Differences in observed hexadecane degradation rates are explained
      on the basis of emulsified hexadecane concentration, cell surface hydrophobicity,
      and cellular localization in the culture.

PMID- 8541986
TI  - Electroporation as an effective means of introducing DNA into abalone (Haliotis
      rufescens) embryos.
AB  - Recombinant plasmid containing the Drosophila beta-actin promoter coupled to a
      beta-galactosidase cassette was linearized and introduced in fertilized eggs of
      the red abalone (Haliotis rufescens) by electroporation. Fertilized abalone eggs
      tolerated electroporation well with larval survival rates between 70% and 84% of
      that for non-electroporated siblings. Dot blot and Southern blot analysis were
      used to detect if abalone retained the foreign gene at various developmental
      stages. The inserted construct was retained in 70% to 100% of all abalone sampled
      with an average of 72% retention in the three- to seven-month-old juveniles.
      Maximal DNA uptake and retention was observed in abalone electroporated at 30-40
      min after fertilization. Southern hybridization analysis suggested that the
      inserted vector was in head-to-tail concantermers integrated in the abalone
      genome. This preliminary study demonstrates that electroporation is an efficient
      means of transferring foreign DNA into abalone embryos.

PMID- 8541987
TI  - A statewide program to evaluate the quality of care provided to persons with HIV
      infection.

PMID- 8541988
TI  - Exemplary quality improvement programs in HMOs.

PMID- 8541989
TI  - A model for practice guideline adaptation and implementation: empowerment of the
      physician.
AB  - The Medical Center model of practice guideline adaptation and implementation uses
      local clinical leaders to evaluate nationally endorsed guidelines, adapt those
      guidelines for use in the local setting, work with support staff to develop and
      apply methods for guideline implementation, and assist the evaluation of clinical
      practice and outcomes data. The model described here combines the guideline
      dissemination techniques of clinical leadership, implementation, and data support
      and feedback. This model overcomes the failures of previous models by
      incorporating local physician involvement during every step of practice guideline
      selection, adaptation, implementation, and evaluation, and by supporting the
      physician leaders with quality data, resources to support guideline
      implementation, and outcomes assessment and feedback.

PMID- 8541990
TI  - The focused review process: a utilization management firm's experience with
      length of stay guidelines.

PMID- 8541991
TI  - Implementing total quality management in health care.

PMID- 8541992
TI  - Promoting collaboration between hospital epidemiology and QI. Interview by Steven
      Berman.

PMID- 8541993
TI  - Pathological case of the month. Idiopathic arterial calcification of infancy.

PMID- 8541994
TI  - Necrotizing fasciitis in children: report of two cases and review of the
      literature.

PMID- 8541995
TI  - The clinical significance of Pseudomonas aeruginosa isolation from stool of
      neonates.

PMID- 8541996
TI  - Hemolytic anemia: an unusual presentation of congenital heart disease.

PMID- 8541997
TI  - Physical abuse with severe hypothermia.

PMID- 8541998
TI  - Removing a major barrier to universal hepatitis B immunization in infants.

PMID- 8541999
TI  - Cigarette smoking cessation programs for parents and children's caregivers: a
      call to children's hospitals and pediatric facilities.

PMID- 8542000
TI  - Securing the future.

PMID- 8542001
TI  - Sexually transmitted diseases, human immunodeficiency virus, and pregnancy
      prevention. Combined contraceptive practices among urban African-American early
      adolescents.
AB  - OBJECTIVE: To evaluate the success of efforts to educate youth not only to use
      prescription contraceptives to avoid pregnancy, but also to use condoms to avoid
      sexually transmitted diseases, including infection with the human
      immunodeficiency virus. METHODS: Longitudinal study of 383 African-American youth
      aged 9 to 15 years enrolled in a randomized, controlled trial of an acquired
      immunodeficiency syndrome (AIDS) risk reduction intervention. Data about
      contraceptive practices were obtained at baseline and 6, 12, and 18 months later
      using a culturally and developmentally appropriate risk assessment tool
      administered with "talking" computers (Macintosh, Apple Computer Inc, Cupertino,
      Calif). RESULTS: Approximately three fourths of sexually active youth used some
      form of contraception in each 6-month round, with almost half of the youth using
      combinations of contraceptives. Among all youth at baseline and among control
      youth throughout the study, more than half used condoms and more than two thirds
      who used oral contraceptives also used condoms. Receipt of an AIDS education
      intervention was associated with use of more effective contraceptive practices
      (eg, condoms and another prescription or nonprescription method of birth
      control). After receiving the intervention, more than 80% of the youth who used
      oral contraceptives also used condoms. Contraceptive practices showed
      considerable stability. Knowledge about AIDS was positively associated with use
      of more effective contraceptive methods. CONCLUSIONS: Many youth are using
      condoms and prescription birth control simultaneously, and these use rates can be
      increased through AIDS education interventions.

PMID- 8542002
TI  - Vitamin A and respiratory syncytial virus infection. Serum levels and
      supplementation trial.
AB  - OBJECTIVE: To determine the benefit of oral vitamin A supplementation for acute
      respiratory syncytial virus (RSV) infection. DESIGN: An observational study of
      vitamin A and retinol binding protein (RBP) levels in RSV-infected inpatients and
      two control groups; and a randomized, controlled trial of vitamin A
      supplementation for RSV-infected inpatients. SETTING: Two tertiary care, urban
      teaching hospitals. PARTICIPANTS: Thirty-two RSV-infected inpatients (aged 2 to
      58 months), 35 hospitalized children without respiratory infections (aged 2 to 19
      months), and 39 healthy outpatient controls (aged 2 to 67 months). INTERVENTION:
      The RSV-infected group was randomized to receive a single dose of 100,000 IU oral
      vitamin A or placebo. MAIN OUTCOME MEASURES: Serum vitamin A and RBP levels of
      all participants and clinical indicators of severity such as days of
      hospitalization, oxygen use, intensive care, intubation, and a daily severity
      score. RESULTS: Mean vitamin a and RBP levels were lower in RSV-infected children
      than in healthy controls (P > .05). Among RSV-infected children, those admitted
      to the intensive care unit had lower mean vitamin A (P  = .03) and RBP levels (P
      = .04) than those not in intensive care. Among children hospitalized without
      respiratory infection, those admitted to the intensive care unit had lower mean
      vitamin A levels (P = .02) than those not in intensive care. In the RSV-infected
      children, no significant difference was seen between the vitamin A group (n = 21)
      and the placebo group (n = 11) in improvement in severity score, mean days of
      hospitalization, intensive care, or receipt of supplemental oxygen. CONCLUSIONS:
      Serum vitamin A and RBP levels were low in children hospitalized with RSV
      infection and were lower in children admitted to the intensive care unit.
      Hospitalized control patients in intensive care also had lower levels than those
      treated on the ward. We observed no benefit from oral vitamin A supplementation
      for children hospitalized with RSV infection.

PMID- 8542003
TI  - Trends and predictors of human immunodeficiency virus antibody testing by
      homosexual and bisexual adolescent males, 1989-1994.
AB  - OBJECTIVE: To identify temporal trends and predictors of human immunodeficiency
      virus (HIV) antibody testing in homosexual and bisexual youth, using the Health
      Belief Model as a conceptual framework. DESIGN: Cross-sectional survey. SUBJECTS:
      Five hundred one male volunteers, 13 to 21 years old, self-identified as
      homosexual, bisexual, or as having sex with men, were enrolled from June 1, 1989,
      to May 30, 1994. METHODS: Structured reviews and written instruments, including
      measures of perceived susceptibility to and severity of HIV disease, benefits and
      barriers to testing, and cues to action. Based on significant (P < .001)
      bivariate association, variables were selected for forward stepwise logistic
      regression analysis. OUTCOME MEASURES: Self-reported HIV antibody testing.
      RESULTS: Forty-five percent of the subjects had undergone HIV antibody testing,
      with no significant differences between annual cohorts. Predictors of testing
      were having discussed same-sex feelings or experiences with a physician or
      counselor, a history of unprotected receptive anal intercourse, substance abuse,
      younger age at self-identification as bisexual or homosexual, ever having had a
      steady male partner, having many friends who understand sexual orientation,
      living away from family, and older age. CONCLUSIONS: Testing practices did not
      change significantly across time. Human immunodeficiency virus testing was
      related to age, risky behaviors, living situation, bisexual or homosexual
      acculturation, and contacts with health professionals, corresponding to Health
      Belief/Model dimensions of perceived susceptibility, barriers, and cues to
      action.

PMID- 8542004
TI  - In search of the Holy Grail.

PMID- 8542005
TI  - Diagnosis of pediatric human immunodeficiency virus infection by means of a
      commercially available polymerase chain reaction gene amplification.
AB  - OBJECTIVE: To assess the sensitivity and specificity of polymerase chain reaction
      (PCR) in infants and children at risk for human immunodeficiency virus (HIV)
      infection. DESIGN: A prospective, blinded study of 286 HIV-seropositive infants
      and children. Infection was diagnosed by antibody detection after 18 months of
      age, two positive direct tests (p24 antigen and HIV culture), or the presence of
      an illness that defines the acquired immunodeficiency syndrome. SETTING:
      University of South Florida and All Children's Hospital, St Petersburg, inpatient
      and outpatient centers. PARTICIPANTS: Two hundred eighty-six infants and children
      seropositive for HIV who were examined between July 1988 and September 1992. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, and predictive values of a
      commercially available PCR test. RESULTS: Five hundred sixty-seven PCR tests were
      performed on samples from 286 seropositive subjects followed up for a minimum of
      16 months. Of the subjects, 105 were confirmed to be infected and 181 uninfected.
      Overall, 96 of 105 initial PCRs in infected subjects were positive (sensitivity,
      91.4%; positive predictive value, 99%). If samples obtained during the first week
      of life are excluded, 95 to 100 samples were positive (sensitivity, 95%). Of 181
      initial PCR tests from seropositive subjects who seroreverted, 180 were negative
      (specificity, 99.4%,; negative predictive value, 95.2%). The predictive value of
      a positive test was 90.9% and that of a negative test was 93.1% in the first
      month of life. All 145 initial samples obtained between 5 weeks and 12 months of
      age correctly predicted infection status (positive predictive value, 100%).
      CONCLUSIONS: Gene amplification by means of a commercially available PCR is
      useful in the diagnosis of HIV infection for infants born to seropositive
      mothers. Between day 7 through 1 year of age, HIV infection is accurately
      diagnosed by the PCR assay.

PMID- 8542006
TI  - Content analysis of prime-time television medical news. A pediatric perspective.
AB  - OBJECTIVES: To assess child health news broadcasts by a major regional television
      station and to evaluate the attitudes of parents and pediatricians about the
      context and value of television news reports. DESIGN: Videotaping 6 months of
      consecutive evening news telecasts (Monday and Friday). Self-administered surveys
      given to a convenience sample of parents and mailed to community pediatricians.
      SETTING: Local and national newscasts of prime-time coverage by a major
      metropolitan television station. PARTICIPANTS: One hundred forty-four members of
      the Buffalo (NY) Pediatric Society and 87 parents of children in the outpatient
      or inpatient departments of The Children's Hospital, Buffalo. RESULTS: Pediatric
      issues were presented in 15% of local and 21% of national medical news stories.
      Adult-specific issues were addressed in 48% of local and 33% of national medical
      news reports. Local pediatric news reports focused on behavior (22%) and major
      illnesses (22%); national pediatric news concentrated on nutrition (30%), allergy
      (21%), and major illnesses (21%). Seventy percent of local and 85% of national
      pediatric news reports referenced an informative source. Fifty-one (59%) of the
      87 parents and 69 (48%) of the 144 pediatricians consider television news to be
      an effective means of increasing awareness of child health issues. Parents and
      physicians recommended pediatric emergencies, safety, disease prevention, and
      adolescent issues as important areas of emphasis for television news. Fifty-one
      percent of the parents (44) and 48% of the pediatricians (69) believed that
      television reports increase knowledge of how to access local health resources.
      CONCLUSIONS: Television news reports are important sources of child health
      information. Pediatric topics on local and national news programs often do not
      focus on topics considered of highest priority by parents and pediatricians.
      Greater awareness by pediatricians of the potential value of television news as a
      tool for public health education is warranted.

PMID- 8542007
TI  - Relationship between behavioral problems and unintentional injuries in US
      children. Findings of the 1988 National Health Interview Survey.
AB  - OBJECTIVE: To investigate (1) the incidence of unintentional injuries among
      children with and without behavioral problems and (2) the role of ethnicity on
      the relationship between behavioral problems and risk for unintentional injuries,
      as unintentional injuries among children represent a major public health concern
      in the United States. DESIGN: Cross-sectional analysis of data on 11 630 children
      contained in the 1988 National Health Interview Survey. MAIN OUTCOME MEASURES AND
      METHODS: We studied the annual incidence of unintentional injury and its
      relationship to child behavioral problems among three ethnic groups (white,
      African American, and Hispanic) through stratified as well as multivariate
      analytic models. RESULTS: Accident rates were higher in white children (17.9%)
      than in African-American (9.3%) or Hispanic (9.3%) children. The odds of
      unintentional injury in children with severe behavioral problems was 1.65 times
      greater than in children without behavioral problems, after controlling for
      relevant sociodemographic characteristics. Ethnicity did not alter the
      relationship between overall behavioral problems and increased injury rates;
      however, ethnic differences emerged in the subscale analysis of disruptive
      behaviors. CONCLUSIONS: Children with behavioral problems represent a significant
      risk group for unintentional injuries among three ethnic groups in the United
      States. These findings emphasize the need to implement accident prevention
      strategies that are specially targeted at children with behavioral disorders.

PMID- 8542008
TI  - Oral prednisone as a risk factor for infections in children with asthma.
AB  - OBJECTIVE: To determine whether the frequency of acute infections in children
      with asthma is associated with the number of doses of prednisone received for
      asthma attacks. DESIGN: A cohort study. SETTING: Primary care clinic and
      emergency department of an inner-city teaching hospital from March 31, 1992, to
      May 31, 1993. PATIENTS: Convenience sample of clinic enrollees aged 2 to 14 years
      who had made two or more outpatient visits for acute asthma in the preceding
      year. Eighty-six children were enrolled. Seventy-eight (91%) completed the study.
      MAIN OUTCOME MEASURES: The independent variable was cumulative prednisone dose
      received during the study period. Outcome variables were episodes of acute
      infections. RESULTS: The mean (+/-SD) number of doses of prednisone (2 mg/kg to a
      maximum of 60 mg) received was 9.5 +/- 11.8 doses (range, 0 to 57 doses). Ninety
      four episodes of acute infection occurred in 50 children. No difference was
      observed in the mean number of doses of prednisone received by those with the
      infection compared with those without the infection. No correlation was observed
      between the number of doses of prednisone received and the number of episodes of
      each infection. CONCLUSIONS: The administration of prednisone as short courses
      for acute asthma is not associated with an increase in the number of episodes of
      common acute infections.

PMID- 8542009
TI  - Depressive symptoms, stress, and social support in pregnant and postpartum
      adolescents.
AB  - OBJECTIVE: To assess prospectively the incidence and course of depressive
      symptoms among pregnant and postpartum adolescents and explore the roles of
      stress and social support as influencing factors. METHODS: Pregnant teenagers
      attending a comprehensive adolescent pregnancy and parenting program were
      enrolled during their third trimester of pregnancy and followed up through 4
      months post partum. Depressive symptoms and social support were measured with
      validated, self-administered instruments during the third trimester and at 2 and
      4 months post partum. Stress was measured during the prenatal and postpartum
      periods. RESULTS: Study participants (N=125) were predominantly black (93%), and
      wee aged 12 to 18 years. Completed assessments were obtained from 114 subjects at
      2 months post partum and 108 at 4 months. Forty-two percent had significant
      depressive symptoms in the third trimester, with 36% and 32% having scores that
      indicated depression at 2 and 4 months post partum. Stress levels increased
      significantly from the third trimester to the postpartum period (P < .01) and
      were positively associated with depressive symptoms. Receiving social support
      from the adolescent's mother or the infant's father, especially in the postpartum
      period, was significantly associated with lower rates of depression. Reporting
      conflict with the infant's father was strongly associated with increased rates of
      depressive symptoms. CONCLUSIONS: Results indicate that depressive symptoms are
      common among pregnant teenagers and postpartum adolescents. Stress and social
      support appear to be important mediators. Identifying those teenagers with high
      stress and conflict and low levels of support will help identify those who are at
      particular risk for depressive symptoms.

PMID- 8542010
TI  - The discriminating value of serum lactate dehydrogenase levels in children with
      malignant neoplasms presenting as joint pain.
AB  - OBJECTIVES: To determine if serum lactate dehydrogenase levels distinguish
      patients with malignant neoplasm presenting with musculoskeletal complaints from
      patients with juvenile rheumatoid arthritis who reported similar symptoms.
      DESIGN: Retrospective case-comparison study. SETTING: Tertiary care, outpatient
      clinics. PATIENTS: Twelve patients with malignant neoplasms who presented with
      arthritis or arthralgias and normal complete blood cell counts and blood smears
      in whom rheumatologic diagnosis was initially made were compared with 24 children
      with a final diagnosis of juvenile rheumatoid arthritis. The patients with
      malignant neoplasms all had normal blood counts and elevated sedimentation rates
      at symptom onset. INTERVENTIONS: None. RESULTS: Serum lactate dehydrogenase
      levels were significantly higher in the cancer patients at 2.2 times the normal
      values vs 0.8 times high normal for patients with juvenile rheumatoid arthritis
      (P =.004, Mann-Whitney U test) No significant differences were observed in white
      blood cell counts, hemoglobin levels, platelet counts, erythrocyte sedimentation
      rate, or uric acid or aspartate aminotransferase levels at initial evaluation.
      CONCLUSIONS: Serum lactate dehydrogenase values may distinguish patients with
      malignant neoplasms from those with rheumatic disease early in the course of
      illness when symptoms and other laboratory values are not helpful.

PMID- 8542011
TI  - Comparison of rectal, axillary, and forehead temperatures.
AB  - OBJECTIVE: To assess whether axillary and forehead temperatures accurately
      reflect the rectal temperature (the criterion standard) DESIGN: Prospective study
      with calculation of paired axillary-rectal and forehead-rectal temperature
      differences and their SDs. SETTING: Referral hospital. PARTICIPANTS: Convenience
      sample of 120 patients, with 20 patients in each of six age groups (ie, < 1
      month, 1 to 5 months, 6 to 11 months, 12 to 23 months, 2 to 14 years, and adults)
      RESULTS: In newborns, the rectal temperature was equal to the axillary
      temperature plus 0.2 degrees C for each week of age up to 5 weeks; forehead strip
      thermometers gave inaccurate readings in this age group. In patients older than 1
      month, the mean difference (SD) between the rectal and axillary temperatures was
      1.04 degrees C (0.45 degrees C); thus the axillary temperature was adjusted by
      adding 1 degree C, and no adjusted axillary temperature differed from the rectal
      temperature by more than 1 degree C. The mean difference (SD) between the
      forehead temperature that was measured by the best forehead liquid crystal strip
      thermometer (FeverScan) and the rectal temperature was 0.14 degrees C (0.60
      degrees C); 10 forehead temperatures differed from the rectal temperature by more
      than 1 degree C. CONCLUSIONS: Previous studies that have suggested that axillary
      and forehead temperatures do not provide a reliable guide to the rectal
      temperature have all used inappropriate methods of analysis (correlation
      coefficients or sensitivity and specificity); previous studies that have based
      their conclusions on the correct method of analysis (paired differences and their
      SDs) have all found that the axillary temperature gives a good indication of the
      rectal temperature. The axillary temperature can be measured safely at any age,
      and the axillary temperature plus 1 degree C is a good guide to the rectal
      temperature in patients older than 1 month. Forehead strip thermometers are easy
      to use, but they do not estimate the rectal temperature as accurately as the
      axillary temperature does.

PMID- 8542012
TI  - Fruit and vegetable intakes of children and adolescents in the United States.
AB  - OBJECTIVES: To identify the ways in which fruits and vegetables are consumed by
      children, to provide estimates of their intakes compared with recommendations,
      and to estimate the percentage of children meeting those recommendations. DESIGN:
      We examined 3 days of dietary data from respondents in the US Department of
      Agriculture's 1989-1991 Continuing Survey of Food Intakes by Individuals. All
      foods reported in the survey were disaggregated into their component ingredients;
      all fruit and vegetable ingredients were assigned specific weights to correspond
      with a serving as defined by current dietary guidance materials; and the number
      of servings of each fruit and vegetable was tallied. PARTICIPANTS: A total of
      3148 children and adolescents aged 2 to 18 years in the 48 conterminous United
      States. MAIN OUTCOME MEASURES: Percentages of fruit and vegetable servings
      consumed in various forms, mean number of servings consumed per day, and
      percentage of persons meeting various recommendations by sex/age, race/ethnicity,
      and household income. RESULTS: Nearly one quarter of all vegetables consumed by
      children and adolescents were french fries. Their intakes of all fruits and of
      dark green and/or deep yellow vegetables were very low compared with
      recommendations. Only one in five children consumed five or more servings of
      fruits and vegetables per day. CONCLUSION: Pediatricians should encourage the
      consumption of fruits and vegetables, especially dark green and deep yellow
      vegetables, by children.

PMID- 8542013
TI  - Professional liability of residents in a children's hospital.
AB  - OBJECTIVE: To evaluate the risk of professional liability to house staff within a
      pediatric hospital setting. METHODS: A retrospective study describing the
      patients, allegations, areas within the hospital where complaints originated, and
      outcome of all malpractice suits involving residents from 1968 through 1992 at a
      large pediatric teaching hospital. RESULTS: There were 49 malpractice cases
      involving residents with or without physicians from 886,000 hospital admissions
      or emergency department visits over the past 20 years (5/5/100,000 patient
      encounters) compared with 185 malpractice cases involving attending physicians
      alone at the hospital (20.5/100,000 patient encounters). The incidence of cases
      originating from the emergency department was 1.8/100,000 compared with
      13.9/100,000 from all other areas of the hospital combined. Fifty-two percent of
      patients had preexisting chronic medical problems. Forty-nine percent of cases
      were settled out of court, 2% went to trial with a decision in favor of the
      plaintiff, 22% were dismissed, and 27% of cases remained open as of June 1993.
      The mean award on behalf of patients from 1968 through 1979 was $580,000 per case
      with a median payment of $163,000. The mean award from 1980 through 1992 was
      $760,000 per case with a median payment of $275,000. CONCLUSIONS: Malpractice
      risk is serious concern for residents and a financial liability for hospitals.
      Resident physicians in a pediatric teaching hospital were named in 26% of
      malpractice cases. Most cases were settled or were dismissed and did not go to
      trial. Risk management training during residency may reduce resident involvement,
      and by extension, the teaching institution's involvement in malpractice
      litigation.

PMID- 8542014
TI  - Open-air schools and the tuberculous child in early 20th-century America.
AB  - In the dead of winter, 1908, the first open-air school in the United States
      commenced class in Providence, RI. Housed on the second floor of an old school
      building in a crowded section of the city, this new school--actually an ungraded
      class in which the enrollment never exceeded 25 pupils--had several novel
      features. Perhaps most striking was that the brick wall on the southern side of
      the room had been removed and replaced with a wall of windows, hinged at the top
      and capable of being raised against the ceiling by means of cords and pulleys.
      Except in driving snow or rain, these windows were kept wide open. To protect
      them against the cold, the children (age range, 6 to 13 years) who were chosen
      for this class because they were sickly, anemic, undernourished, or showing early
      signs of tuberculosis and because, owing to their ill health, they had failed to
      make adequate progress in advancing to the next grade, were outfitted in wool
      sweaters, mittens, caps, and felt overshoes and were encased in "Eskimo" or
      sitting-out bags that resembled present-day sleeping bags.

PMID- 8542015
TI  - Radiological case of the month. Membranous laryngotracheobronchitis.

PMID- 8542016
TI  - Picture of the month. Acrodermatitis enteropathica-like rash in cystic fibrosis.

PMID- 8542017
TI  - Red cell membrane polypeptides under normal conditions and in genetic disorders.
AB  - Broadly speaking, the red cell membrane is comprised of --a cholesterol-rich
      phospholipid bilayer that is studded by a large number of trans-bilayer proteins,
      --of glycosylphosphatidylinositol-anchored proteins (GPI-proteins) standing
      outside, and --an important protein assembly, the erythrocyte or membrane
      skeleton, that laminates the inner surface of the bilayer. Among the trans
      bilayer proteins, one finds the anion exchanger, the glycophorins, the glucose
      transporter, a variety of cation transporters and pumps, and of course proteins
      carrying the epitopes of many blood groups. Among the GPI-proteins, one
      encounters the acetylcholinesterase and the decay-accelerating factor (CD 55).
      Among the skeletal proteins, finally, one recognises spectrin, actin (and a
      number of actin-binding proteins other than spectrin: dematin, tropomyosin,
      tropomodulin, etc.), protein 4.1 and protein p55. Spectrin heterotetramer
      organizes into a bidimensional network with a hexagonal mesh on the average. This
      network is linked to trans-bilayer proteins, through the complex beta-spectrin
      ankyrin-anion exchanger (+ protein 4.2) on the one hand and, on the other hand,
      through the triangular interaction between protein 4.1, glycophorin C and protein
      p55. The sequence of the above proteins and the exon-intron organisation of their
      genes are known in most cases. Many proteins have a widespread tissue
      distribution in the form of variants adapted to their local functions. Such
      variants may be the products of multigene families (anion exchanger, ankyrin,
      spectrin), or derive from a single gene (protein 4.1, protein 4.2), the
      transcripts of which undergo cell-specific alternative splicing. It has been
      established that many congenital haemolytic anaemias result from mutations
      altering the above-mentioned genes. We will provide two examples. Hereditary
      elliptocytosis stems from an array of mutations located at, or near the head-to
      head self-association region of two spectrin alpha beta dimers, or from mutations
      which, most often, yield a reduction (heterozygous state) or the lack (homozygous
      state) of protein 4.1. The aggravation of elliptocytosis associated with alpha
      spectrin mutations frequently yields poikilocytosis and usually stems from the
      occurrence, in trans, of a low expression allele, allele alpha LELY. Hereditary
      spherocytosis derives from mutations in the ankyrin gene (80% of the cases), the
      anion exchanger gene (10-15% of the cases), the protein 4.2 gene (rare cases) and
      the alpha- and beta-spectrin genes (rare cases). Anion exchanger mutations
      usually cause the decrease in this protein (heterozygous state).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8542018
TI  - European School of Transfusion Medicine Residential Course. Paris, 26-29 April
      1995.

PMID- 8542019
TI  - Biochemical approaches to the detection and characterization of membrane proteins
      carrying blood group determinants.
AB  - The investigation of red blood cell membrane proteins carrying blood group
      determinants mainly involves the use of specific antibodies--polyclonal human
      antibodies and both murine and human monoclonal antibodies--directed against
      blood group antigens. Other blood group specific reagents like lectins, also
      represent useful tools to identify membrane proteins. These reagents allowed the
      detection and, then the characterization of several red cell membrane components
      by using a series of methods based on their specific interaction with the
      corresponding antigen. Reagents and investigation methods are overviewed
      hereafter.

PMID- 8542020
TI  - Biochemical characterization of blood group-active glycosphingolipids.
AB  - Glycosphingolipids are quantitatively minor components of cell lipids. However,
      their segregation in the outer leaflet of the plasma membrane confers to these
      membranes specific structural and immunological properties. Current methods of
      extraction, purification and analysis of blood cell glycolipids are presented.
      Valuable structural data may be obtained by a combination of chemical and
      enzymatic degradations with thin-layer chromatography and immunological detection
      by monoclonal antibodies of known specificity. Examples of physical
      characterization by Mass Spectrometry and Proton Magnetic Resonance Spectroscopy
      are also presented.

PMID- 8542021
TI  - Molecular genetics of H, Se, Lewis and other fucosyltransferase genes.
AB  - Seven human fucosyltransferase genes have been cloned and registered in the
      Genome Data Base (GDB) as FUT1 to FUT7. According to their acceptor specificity,
      two main groups of enzymes can be distinguished. The alpha-2-fucosyltransferases:
      FUT1 (H) of red cells and vascular endothelium and FUT2 (Se) of exocrine
      secretions. The alpha-3-fucosyltransferases: FUT3 (Lewis) of exocrine secretions;
      FUT4 (myeloid) of white cells and brain; FUT5 whose tissue distribution has not
      been defined as yet; FUT6 (plasma) present in plasma, renal proximal tubules and
      hepatocytes; FUT7 (leukocyte) found in neutrophils. A high DNA sequence homology
      has been detected among the genes within each of these two groups, while no
      homology has been detected between the genes of the two groups. Point mutations
      responsible of inactivating genetic polymorphisms have been found for FUT1, FUT2,
      FUT3 and FUT6, while FUT4 and FUT7 seem to be genetically monomorphic. FUT4 has
      been detected in all tissues of 5 to 10 weeks old human embryos suggesting that
      it may play a role in development. FUT7 is a candidate for the control of the
      synthesis of the receptors of selectin mediated cell adhesion.

PMID- 8542022
TI  - The Kell blood group system.
AB  - The Kell blood group system is complex containing over 20 different antigens.
      Some of the Kell antigens may be organized in 5 sets of paired alleles with
      opposing high and low incidence antigens while others are independently
      expressed. Molecular cloning established that Kell antigens are carried on a
      93kDa, type II, membrane glycoprotein. The Kell gene (KEL) is located at 7q 32-36
      and spans about 21,5 kb. The coding sequence is organized in 19 exons. The
      promoter region does not contain TATA sequences but has possible transcription
      binding sites for GATA-1 and Sp1. Kell protein shares a putative enzymatic active
      amino acid sequence with a large family of zinc endopeptidases and has closest
      structural and sequence homology with neutral endopeptidase 24,11 (a.k.a.
      enkephalinase, CALLA) and endothelin converting enzyme (ECE-1). The molecular
      basis of several important Kell antigens has been determined and all are due to
      base substitutions causing single amino acid changes. The K1/K2 polymorphism is
      due to a C to T substitution in exon 6, encoding a threonine to methionine
      change. This mutation disrupts an N-glycosylation site. Two PCR-based methods,
      including use of allele-specific primers, have been developed which may be used
      to determine fetal K1/K2 genotypes. These tests can potentially identify those
      pregnancies at risk for hemolytic disease of the newborn. The allelic
      relationship of Kpa, Kpb and Kpc was confirmed, since single base substitutions
      in the same codon encode 3 different amino acids.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8542023
TI  - MNSs and major glycophorins of human erythrocytes.

PMID- 8542024
TI  - Gerbich blood groups and minor glycophorins of human erythrocytes.
AB  - Four main glycophorins which can be specifically detected by periodic-acid-Schiff
      (PAS) staining after separation of red cell membranes by SDS-polyacrylamide gel
      electrophoresis have been identified and are known under different nomenclatures.
      Here, the designation of glycophorins A, B and C and glycophorin D will be used.
      A new member designated glycophorin E (GPE) has been recently identified in the
      course of molecular genetic studies. These glycophorins represent about 2% of the
      total erythrocyte membrane protein mass and have been fully characterized both at
      the protein and at the DNA level. Accordingly, these molecules can be subdivided
      into two groups that are distinguished by distinct properties such as blood group
      antigenic properties, apparent M(r), copy number, attached glycans, detergent
      solubility, and gene structure. GPC and GPD are minor sialoglycoproteins
      contributing to 4 and 1% to the PAS-positive material and are present at about
      2.0 and 0.5 x 10(5) copies/cell, respectively. Both carry blood group Gerbich
      (Ge) antigens. Protein and nucleic acid analysis indicated that GPD is a
      truncated form of GPC in its N-terminal region and that both proteins are
      produced by a unique gene which is present as a single copy on chromosome 2q14
      q21. GPC and GPD are produced from the same gene through use of alternative
      translation initiation sites. These proteins and the GYPC gene share no homology
      with the GPA, GPB and GPE proteins and the GYPA gene cluster, respectively. Thus,
      the glycophorin name, which suggests that all these sialoglycopropteins have a
      common genetic origin, might be now considered as a misnomer. As a further
      difference between the two groups of membrane proteins, GPC and GPD are expressed
      both in erythroid and non erythroid tissues, but the level of transcription is
      much higher in erythroid than in non erythroid tissues and in addition the
      proteins are differently glycosylated in the two cell types. Increasing evidence
      suggests a significant role for GPC and GPD in the regulation of the red cell
      shape and the membrane mechanical properties by providing a membrane linkage site
      for cytoskeletal proteins, especially proteins 4.1 and p55. The total lack of GPC
      and GPD in the red cell membrane is associated with hereditary ellyptocytosis in
      the Leach phenotype and the molecular basis of these defects have been
      elucidated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8542025
TI  - Duffy and receptors for P. vivax and chemotactic peptides.
AB  - The Duffy blood group system consists of two principal antigens, Fya and Fyb
      produced by FY*A and FY*B co-dominant alleles. Antisera, anti-Fya and anti-Fyb,
      define four phenotypes: Fy(a+b-), Fy(a-b+), Fy(a+b+) and Fy(a-b-). Neither
      antiserum agglutinates Fy(a-b-) cells, the predominant phenotype in Blacks.
      Outside the Black population, Fy(a-b-) phenotype is very rare. Duffy antigens
      appear to be multimeric erythrocyte-membrane proteins composed of different
      subunits. A glycoprotein of 35-45 kDa, gp-Fy, is the major subunit of the complex
      and has antigenic determinants defined by Duffy antibodies. The protein consists
      of 337 amino acid residues with a M(r) of 35,733, the same as deglycosylated gp
      Fy. The hydropathy map predicts an exocellular N-terminal domain of 64 residues,
      nine transmembrane alpha-helices, three short protruding hydrophilic loops and an
      endocellular C-terminal domain of 23 residues. Duffy specific transcript, a
      approximately 1.3 kb mRNA, is produced by the bone marrow of Duffy-positive
      individuals, but it is not produced by the bone marrow of Duffy-negative
      individuals. The same size mRNA is produced in many tissues of Duffy-positive
      individuals. The same tissues of Duffy-negative individuals also synthesize the
      same size mRNA and the same gp-Fy as that of Duffy-positive individuals. There is
      not, therefore, Duffy null phenotype in the Black population. The difference
      between FY*A and FY*B alleles is a single nucleotide change at position 306;
      guanine is in FY*A, and adenine is in FY*B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542026
TI  - Glycosyl phosphatidylinositol-linked blood group antigens and paroxysmal
      nocturnal hemoglobinuria.
AB  - Human erythrocyte cell surface molecules that are attached to the cell membrane
      by glycosyl-phosphatidylinositol (GPI) anchors include the complement regulatory
      proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive
      lysis (MIRL, CD59), as well as the proteins that bear the Cartwright, Dombrock,
      and JMH blood group antigens. The acquired hematopoietic stem cell disorder
      paroxysmal nocturnal hemoglobinuria (PNH) results from the absence or marked
      deficiency in expression of GPI-anchored proteins in affected hematopoietic
      cells. PNH usually if not always results from a somatic mutation of an X-linked
      gene called PIG-A; the product of the PIG-A gene is a glycosyl transferase
      necessary for construction of the GPI anchor. DAF is a ubiquitously expressed
      protein present in many tissues, including gastrointestinal epithelia, corneal
      epithelia, and serosa of urinary and reproductive organs. DAF is a 70 kD
      glycoprotein containing complement regulatory short consensus repeats (SCRs); its
      gene is located in the regulation of complement activation (RCA) gene cluster on
      chromosome 1 and is about 40 kb in size. The Cromer blood group antigens, which
      reside on DAF, include 10 currently defined antigens, of which seven are of high
      incidence. The molecular basis of the Cr (a-) phenotype has been determined to be
      a single base pair substitution in DAF SCR4 (G-->C, leading to an ala193 to pro
      amino acid substitution). The Tc alpha antigen appears to be determined by the
      amino acid sequence of SCR1, with the Tc (a-b+) phenotype arising from a base
      pair substitution of G55-->T, leading to an arg18 to leu amino acid substitution.
      The null phenotype for Cromer antigens occurs when DAF is completely absent; only
      one example has been completely studied on the molecular level. That individual
      is homozygous for a point mutation in SCR1 (G314-->A) that creates a stop codon
      (TGA) in place of one normally encoding trp53 (TGG) and thus prevents further
      translation of the mRNA. The Dr(a-) phenotype expresses reduced quantities of DAF
      (approximately 40% of normal levels), as well as a polymorphism of DAF. Lack of
      the Dr alpha antigen has been proved to result from a single point mutation in
      SCR3 (C-->T in codon 165) that leads to a single amino acid substitution (ser-
      >leu). The Cartwright (Yt) antigens reside on acetylcholinesterase (AChE). In
      erythroid cells, a small exon that encodes the signal for attachment of the GPI
      anchor is retained in a tissue-specific process.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8542027
TI  - Lutheran antigens, CD44-related antigens, and Lutheran regulatory genes.
AB  - The Lutheran (Lu) blood group antigens are a family of human erythrocyte antigens
      which reside on two closely-related erythrocyte integral membrane proteins.
      Sixteen Lutheran or so-called para-Lutheran antigens have thus far been
      described, and human antisera to many of them have been shown to immunoblot two
      proteins, of 78 and 85 kDa. Lu cDNA encodes an integral membrane protein of 597
      amino acids that is a member of the Ig superfamily. Lu proteins comprise five Ig
      superfamily domains, along with a single transmembrane domain and a cytoplasmic
      domain of about 60 amino acids. The two proteins seen in biochemical studies of
      red cell membranes appear to be derived from 2 mRNA species that differ only in
      their 3' ends, suggesting that they arise from alternate splicing of a single
      preRNA. Three genetic backgrounds for the Lu(a-b-) [Lu null] phenotype have been
      described. A recessive Lu null phenotype is rarely observed as a result of
      homozygosity for two amorphic LU alleles. However, the most common Lu(a-b-)
      phenotype appears to be caused by an independently segregating, dominant gene,
      designated In (Lu), which inhibits expression of all Lutheran antigens to nearly
      undetectable levels. This gene also affects the expression of other cell surface
      proteins and blood group antigens that are genetically unlinked to the Lutheran
      locus, including CD44 and MER2. CD44, a member of the cartilage link family of
      proteins, bears the In and AnWj blood group antigens. A widely distributed
      protein CD44 is expressed at normal levels on all tissues except erythrocytes in
      the presence of the In (Lu) gene. A second Lutheran regulatory gene, XS2, is
      responsible for the third Lu(a-b-) phenotype, which exhibits an X-linked
      inheritance pattern. The XS2 gene down-regulates but does not abolish expression
      of LU genes and does not affect expression of CD44.

PMID- 8542028
TI  - ABH and Colton blood group antigens on aquaporin-1, the human red cell water
      channel protein.
AB  - The recent identification of the red cell water transporter (AQP1) has led to the
      identification of the "aquaporins", a new class of membrane proteins which
      function as water-selective transport proteins and are involved in many
      physiological processes. Identification of the chromosomal localization of the
      corresponding gene led to the recognition that AQP1 is the structural basis of
      the Colton blood group antigens. Analysis of individuals with the Colton null
      phenotype led to the recognition that homozygosity for knockout mutations in the
      corresponding gene is exceedingly rare but is without a significant clinical
      phenotype, predicting a redundancy in expression of other aquaporin homologs.
      These studies demonstrate the importance which molecular studies in red cell
      blood group antigens may play in diverse areas of biomedical research. Moreover,
      they provide another example that blood group antigens may be polymorphisms in
      functionally important proteins on the red cell surface.

PMID- 8542030
TI  - Rh haemolytic disease of the newborn and Rh genotyping by RFLP--and allele
      specific--PCR.

PMID- 8542029
TI  - Urea transport and Kidd blood groups.
AB  - The gene encoding for the human erythrocyte urea transporter (HUT11 clone) has
      recently been cloned (Olives et al., J. Biol. Chem., 269, 3/649, 1994). It has
      been localized at 18q12-q21, like the Kidd blood group gene. In vitro translation
      experiments indicated that cDNA HUT11 could induce the synthesis of a 36 kDa
      protein which can be immunoprecipitated by an anti-Jk3 antibody (a human antibody
      produced by Jk(a-b-) individuals). This antibody also precipitates a 46-60 kDa
      protein from human red blood cells, except from those with Jk(a-b-) phenotype.
      After N-glycanase digestion, the length of the glycoprotein was reduced from 46
      60 kDa to 36 kDa. Moreover, a rabbit antibody directed against the N-terminal end
      of HUT11 protein reacts in western-blot with 46-60 kDa proteins present in all
      human red blood cells, except those with Jk(a-b-) phenotype. Jk(a-b-) cells have
      neither Kidd protein nor HUT11 urea transporter and they are characterized by a
      selective defect of urea transport whereas water transport and aquaporin-1
      associated Colton antigens are normally expressed. All these findings provide
      evidence that the Kidd locus encodes for the human erythrocyte urea transporter,
      offering new prospects for biological study of urea transporters and their tissue
      specific regulation.

PMID- 8542031
TI  - DNA markers in forensic medicine.
AB  - After a description of the various DNA polymorphisms which can be used in
      forensic medicine, the use of these markers for solving cases of disputed
      paternity is discussed in detail. VNTR polymorphisms detectable after
      amplification of the relevant loci by the PCR seem to be the best tools for
      paternity testing.

PMID- 8542032
TI  - The future of blood groups and other markers in reference laboratories.
AB  - Erythrocyte blood group-reference laboratory activities have to develop in
      accordance with new scientific knowledge brought by molecular biology. Reference
      laboratories will have to use immunology as well as molecular biology for a long
      time yet; both approaches are complementary. Recombinant cells expressing
      specific antigens will thus be used in parallel to red blood cells with selected
      phenotype combinations. To be efficient, Reference laboratory activities must be
      performed together with research and education activities with a view to
      spreading knowledge within a national network.

PMID- 8542034
TI  - Neuromuscular diseases: muscle.

PMID- 8542033
TI  - Neuromuscular diseases: nerve.

PMID- 8542035
TI  - Epidemiology of peripheral neuropathy.

PMID- 8542036
TI  - Electrodiagnosis.
AB  - Attempts to increase the diagnostic yield and reproducibility of
      electrophysiological investigation of peripheral nerve disorders have led to the
      development of new techniques, such as measurement of nerve refractoriness, as
      well as the re-evaluation, refinement and modification of more conventional nerve
      conduction tests. Other studies have characterized the clinical and
      electrophysiological features of the subtypes of polyneuropathies associated with
      monoclonal gammopathies and have documented their natural history, providing
      important diagnostic and prognostic information. Techniques originating in basic
      neuroscience that study the excitability of neurons and nerve membranes have been
      applied to clinical conditions, such as motor neuron disease and cramps, and have
      provided considerable insight into their pathogenesis.

PMID- 8542037
TI  - Nerve biopsy.
AB  - For many years, nerve biopsy has been very useful for clarifying the mechanism
      and aetiology of human peripheral neuropathies. Recently, this morphological
      examination has greatly benefited from the contribution of new
      immunocytochemical, ultrastructural and molecular biological techniques, which
      can often be used together in studies on inflammatory, paraproteinaemic and
      genetic neuropathies.

PMID- 8542038
TI  - Immunological investigation.
AB  - This review describes recent efforts to identify the immunological mediators of
      inflammatory neuropathy. Although particular emphasis is given to the origin,
      specificity and effects of antiglycolipid antibodies, progress in the role of
      cytokines and adhesion molecules has also been reported.

PMID- 8542039
TI  - Nerve regeneration.
AB  - The regeneration of nerve is a brilliant example of plasticity within the nervous
      system. Axonal sprouts form within a few hours of nerve injury and grow
      vigorously over long distances. Nonetheless, recovery from nerve injury, such as
      that seen after laceration of distal motor-sensory nerve, is often incomplete. A
      variety of approaches to enhance peripheral nerve regeneration are currently
      being pursued. They include the use of electric fields, treatment with
      neurotrophic factors and Schwann cell manipulation.

PMID- 8542040
TI  - Multifocal motor neuropathy and chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - In multifocal motor or sensorimotor neuropathy with persistent conduction block,
      most of the recent research has concerned treatment. Open trials show that
      intravenous immunoglobulin is effective, providing a rapid and often marked
      clinical improvement, accompanied by a significant reduction of conduction block
      in some cases, but without any significant change in the titre of anti
      ganglioside GM1 antibodies. However, long-term therapy with intravenous
      immunoglobulin seems to bring less improvement than expected, and further trials
      are needed to study the efficacy of other immunosuppressive drugs, such as oral
      or intravenous cyclophosphamide. These treatments may also benefit acquired lower
      motor neuron diseases with a progressive course, high anti-ganglioside GM1 titres
      and no conduction block. In chronic inflammatory demyelinating polyneuropathy,
      recent articles have reported interesting immunopathological,
      electrophysiological and immunochemical features. This syndrome seems to be
      heterogeneous. Therefore, better criteria need to be defined, particularly so
      that an informed choice can be made as to the most appropriate treatment. A
      recent controlled trial has shown that intravenous immunoglobulin infusion may be
      as effective as plasma exchange in the short-term therapy of chronic inflammatory
      demyelinating polyneuropathy.

PMID- 8542041
TI  - Diabetic neuropathy.
AB  - The possible role of growth factors in diabetic neuropathy is under investigation
      and offers new insights into the effect of diabetes on nerve function. The search
      continues to identify the pathogenic mechanisms involved, many of which will be
      interlinked.

PMID- 8542042
TI  - Toxic neuropathies.
AB  - Current publications describe neurotoxic effects of metals, pharmaceutical
      products, and environmental, biological and experimental substances. Agents such
      as lead remain the object of new epidemiological methods to identify victims. The
      use of methylcobalamin to ameliorate acrylamide toxicity is being explored.
      Antiarrhythmic and antilipidemic drugs continue to be associated with neuropathic
      effects but appear to be amenable to adjustments in dosage. To help control the
      neurotoxic effects of the chemotherapeutic drugs taxol and cisplatin analogs of
      adrenocorticotropic hormone and neurotrophic factors are being used. A new
      immunosuppressant, FK 506, has replaced cyclosporin to facilitate organ
      transplantation, but unwanted effects, including peripheral neuropathy, have been
      documented in some patients. In experimental studies, FK 506 has been reported to
      accelerate the rate of nerve regeneration. Botulinum toxin for the treatment of
      localized spastic disorders is a useful therapy, but training and supervision has
      been recommended by the American Academy of Neurology. Experimental toxins, such
      as imminodipropionitrile, continue to provide useful insights into physiologic
      mechanisms, including the axonal transport of cytoskeletal components.

PMID- 8542043
TI  - Free radicals, programmed cell death and muscular dystrophy.

PMID- 8542044
TI  - Dystrophin-glycoprotein complex: molecular organization and critical roles in
      skeletal muscle.
AB  - Recent molecular and biochemical studies have disclosed the detailed molecular
      organization of the dystrophin-glycoprotein complex, which links the cytoskeleton
      to the extracellular matrix. Defects in several components of this complex cause
      different types of muscular dystrophy. This glycoprotein complex is also involved
      in clustering and anchoring acetylcholine receptors at the postsynaptic membrane.

PMID- 8542045
TI  - Congenital muscular dystrophies.
AB  - Considerable advances in the understanding of congenital muscular dystrophy made
      during the past year may allow a new clinical classification of this disease. In
      particular, (1) evidence has accumulated to suggest that a laminin alpha2-chain
      (alpha2 subunit of laminin-2 or merosin) deficiency causes a type of congenital
      muscular dystrophy, and (2) it has been postulated that Fukuyama-type congenital
      muscular dystrophy and Walker-Warburg syndrome (but not Finnish muscle-eye-brain
      disease) are genetically identical diseases.

PMID- 8542046
TI  - Inherited disorders of contractile proteins in skeletal and cardiac muscle.
AB  - The functional unit of muscle contraction is the sarcomere, a structure of strict
      cytoarchitecture constructed from a relatively small number of mostly identified
      contractile proteins. The messenger RNAs for seven muscle proteins combined
      together account for 20% of all the messenger RNA in mature muscle fibres. It
      should be anticipated that mutations in these and other highly expressed messages
      or proteins will cause inherited muscle disorders. In recent years, but
      especially in the past 12 months, disorders associated with some of these
      proteins have been identified. Familial hypertrophic cardiomyopathy, central core
      disease, nemaline myopathy, and autosomal recessive limb-girdle muscular
      dystrophy have all been shown to involve mutations in proteins associated with
      the sarcomere.

PMID- 8542047
TI  - Discordance between phenotype and genotype in malignant hyperthermia.
AB  - Eight mutations in the ryanodine receptor gene on human chromosome 19q13.1 have
      been linked to malignant hyperthermia. Although 50% of malignant hyperthermia
      families are not linked to the ryanodine receptor gene, only single malignant
      hyperthermia families have been linked to alternative loci on chromosome 7q21-22
      and on chromosome 3q13.1. Problems in malignant hyperthermia linkage studies may
      arise from the inadequacy of the caffeine halothane contractures test for
      phenotypic diagnosis of malignant hyperthermia.

PMID- 8542048
TI  - Hereditary nondystrophic myotonias and periodic paralyses.
AB  - The hereditary disorders of muscle excitability are now recognized to be caused
      by defects in the genes encoding muscle ion channels. This led to a new
      classification of this disease group. The pathophysiology of these disorders has
      been elucidated on the molecular level to an extent that exceeds the
      understanding of the disease mechanisms of most other neuromuscular diseases. The
      seemingly minor variants of the symptom of myotonia were found to be caused by
      the remarkable difference that either chloride or sodium channel function is
      impaired. Even more surprising, the basic defects for hyper- and hypokalemic
      periodic paralysis, often clinically very difficult to distinguish, turned out to
      be in the sodium and calcium channels, respectively; these channels are
      considered to have very different functions in muscle physiology. Three new types
      of myotonic disease, that is, myotonia, fluctuans, myotonia permanens and
      proximal myotonic myopathy were discovered. An explanation has been provided as
      to why myotonia congenita may be transmitted as a dominant or recessive trait.

PMID- 8542049
TI  - The SPIRITual history.
AB  - Spirituality can be defined as a belief system focusing on intangible elements
      that impart vitality and meaning to life's events. Often spirituality is
      expressed through formalized religions. Recently, the interplay of spirituality,
      religion, and health care has been explored in the medical literature. Spiritual
      belief systems impact on the incidences, experiences, and outcomes of several
      common medical problems. Unfortunately, there is little recent literature
      addressing the process of conducting a medically oriented spiritual history. One
      approach to assisting the physician in spiritual history taking, a mnemonic,
      SPIRIT, is presented as a guide to identifying important components of the
      spiritual history. This article addresses the issues of when and whom to
      interview, as well as specific professional and ethical issues related to this
      topic. Two case examples from my practice are presented to illustrate the utility
      of the SPIRITual history.

PMID- 8542050
TI  - Effects of benazepril and hydrochlorothiazide, given alone and in low- and high
      dose combinations, on blood pressure in patients with hypertension.
AB  - OBJECTIVE: To assess the efficacy and safety of several combinations of
      benazepril, an angiotensin-converting enzyme inhibitor, and hydrochlorothiazide,
      as compared with placebo, in the treatment of patients with essential
      hypertension. DESIGN: A 6-week, randomized, double-blind, parallel study
      conducted at 24 centers. A placebo run-in period of 1 to 4 weeks preceded the
      double-blind phase. PARTICIPANTS AND SETTING: Male and female outpatients, aged
      18 years and older, were eligible to participate if their sitting diastolic blood
      pressure was between 95 and 114 mm Hg at the last two consecutive visits during
      the placebo phase. Among the 334 patients who entered the double-blind phase, 17%
      were aged 65 years or older and 26% were black. Eleven patients withdrew because
      of adverse experiences, including two patients receiving placebo. INTERVENTIONS:
      Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg; or
      combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg, 10/12.5 mg,
      20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks. MAIN OUTCOME MEASURES:
      The mean change from baseline in sitting diastolic blood pressure at end point
      (last postrandomization measurement carried forward) in the double-blind phase.
      Combination therapy with benazepril/hydrochlorothiazide, 20/25 mg, was compared
      with benazepril, 20 mg alone, and hydrochlorothiazide, 25 mg alone. Sitting
      systolic blood pressure and the effect of race and age on treatment efficacy were
      also evaluated. RESULTS: Compared with placebo, all
      benazepril/hydrochlorothiazide combinations produced statistically significant
      reductions from baseline in sitting diastolic and systolic blood pressures at
      study end point. In the benazepril/hydrochlorothiazide, 20/25 mg, group, the
      adjusted mean changes in sitting diastolic blood pressure at end point were
      statistically significantly greater than those in the monotherapy treatment
      groups (benazepril, 20 mg, P < or = .05; hydrochlorothiazide, 25 mg, P < or =
      .001) alone. All therapies were generally well tolerated. Decreases in mean serum
      potassium level with hydrochlorothiazide monotherapy were reduced or eliminated
      with combination therapy. CONCLUSION: Benazepril in combination with
      hydrochlorothiazide, including a low-dose combination of 5/6.25 mg, is effective
      in reducing sitting diastolic and systolic blood pressure in patients with
      hypertension.

PMID- 8542051
TI  - Prevalence of comorbid anxiety disorders in primary care outpatients.
AB  - OBJECTIVE: To estimate the extent to which anxiety disorders (eg, panic disorder,
      phobia, and generalized anxiety disorder [GAD]) co-occur in patients with major
      medical and psychiatric conditions. DESIGN: Observational study. SETTING: Offices
      of primary care providers in three US cities, with mental health specialty
      providers included for comparative purposes. PATIENTS: Adult patients (N = 2494)
      with hypertension, diabetes, heart disease (congestive heart failure or
      myocardial infarction), current depressive disorder, or subthreshold depression.
      MEASURES: Current (past 12 months) and lifetime panic disorder, phobia, GAD,
      perceived need for help for emotional or family problems, and unmet need (ie,
      failure to get help that was needed). METHODS: Comparisons of the prevalence of
      anxiety comorbidity in medically ill nondepressed patients of primary care
      providers and in depressed patients of both primary care and mental health
      specialty providers. RESULTS: Among primary care patients, those with chronic
      medical illnesses or subthreshold depression had low rates of lifetime (1.5% to
      3.5%) and current (1.0% to 1.7%) panic disorder, but those with current
      depressive disorder had much higher rates (10.9% lifetime and 9.4% current panic
      disorder). Concurrent phobia and GAD were more common (10.4% to 12.4% current
      GAD), especially among depressed patients (25% to 54% current GAD). Depending on
      the type of medical illness or depression, 14% to 66% of primary care patients
      had at least one concurrent anxiety disorder. Patient-perceived unmet need for
      care for personal or emotional problems was high among all primary care patients
      (54.6% to 72.9%). CONCLUSION: Primary care clinicians should be aware of the
      possible coexistence of anxiety disorders (especially GAD) among their patients
      with chronic medical conditions, but especially among those with current
      depressive disorder.

PMID- 8542052
TI  - Use of a pharmacy and medical claims database to document cost centers for 1993
      annual asthma expenditures.
AB  - OBJECTIVE: To demonstrate the utility of a combined pharmacy and medical claims
      database in the assessment of the incidence and the cost centers of asthma care
      in a managed health care system. DESIGN: A retrospective observational study to
      document annual cost for asthma therapy by cost center during 1993. SETTING: Four
      affiliated health maintenance organizations. PARTICIPANTS: A total of 25,614
      asthmatics identified from a population of approximately 673,000 members in the
      health maintenance organization. INTERVENTIONS: None. MAIN OUTCOME MEASURE:
      Annual charges by cost center for asthma care analyzed by age and gender.
      RESULTS: The period prevalence of asthma was 3.8%. Annual direct medical charges
      for asthma were $467.40 per member. Inpatient hospital and emergency department
      charges were greater in children than adults. Adolescent girls had increased use
      of the emergency department and inpatient hospital facilities and lower charges
      for medications than their male counterparts. Their increased use of acute care
      facilities was responsible for 25% greater charges for total asthma care. The
      gender differences in cost centers continued for adults, with increased charges
      for inpatient hospital and emergency department charges and lower expenses for
      medications for women. CONCLUSIONS: Charges for acute care were inversely related
      to the dollars spent on pharmaceuticals. This study demonstrates the ability of a
      combined medical and pharmacy database to document the charges for care and
      possibly identify indicators of undertreated populations.

PMID- 8542053
TI  - Shingles in one family practice.
AB  - One hundred twenty-four patients presented with herpes zoster in a small-town,
      solo practice between 1983 and 1992. This article reviews the clinical features
      and natural history of herpes zoster, followed by a description of the cases seen
      in the study practice. This common disease, easily diagnosed and treated by the
      family physician, usually responds well to treatment with acyclovir.

PMID- 8542054
TI  - Identification of Turner's syndrome in an elderly woman. Case report and review.
AB  - Turner's syndrome is one of the most frequently occurring chromosomal defects and
      is associated with a well-characterized set of anatomic malformations. We studied
      clinical findings in an elderly woman who was diagnosed as having cytogenetically
      proved Turner's syndrome late in life. Because most patients with Turner's
      syndrome have normal intelligence and mild phenotypic abnormalities, the
      condition was never properly diagnosed in many affected women born earlier in
      this century. Given the range of clinical abnormalities and physiologic deficits
      to which these women are predisposed, it remains important to diagnose and treat
      them accurately irrespective of age.

PMID- 8542055
TI  - Pathology in family practice. Instraspinal dermoid cyst.

PMID- 8542056
TI  - Inappropriate guilt over benzodiazepine prescription.

PMID- 8542057
TI  - Physiological and morphological heterogeneity of dentate gyrus-hilus interneurons
      in the gerbil hippocampus in vivo.
AB  - A variety of morphological types of dentate gyrus/hilus interneurons have been
      described, but little is known about their corresponding physiological
      characteristics. To address this issue, intracellular responses to current
      injection and perforant path stimulation were obtained from putative dentate
      interneurons in anaesthetized adult gerbils. Our sample of interneurons showed
      heterogeneity in their intrinsic physiological characteristics and spike
      thresholds to perforant path stimulation, suggesting the existence of distinct
      physiologically-defined classes. 'Fast-spiking' interneurons had a low threshold
      to perforant path stimulation, whereas 'slow-spiking' interneurons responded with
      predominantly inhibitory potentials. In several cases, cells were intracellularly
      labelled with biocytin for visualization. Interneurons with different
      physiological traits had distinct morphological features. These results confirm
      that, as in hippocampus proper, morphologically identifiable interneurons in the
      dentate hilus show electrophysiological features that are likely to reflect
      functionally specific roles in informational processing.

PMID- 8542058
TI  - Biphasic expression of the fos and jun families of transcription factors
      following transient forebrain ischaemia in the rat. Effect of hypothermia.
AB  - Transient global ischaemia induces the expression of immediate early genes. Using
      in situ hybridization, the expression of c-fos, fosB, fra-1, fra-2, c-jun and
      junB was studied after 15 min of normothermic and hypothermic (33 degrees C)
      transient forebrain ischaemia in the rat, induced by common carotid occlusion
      combined with systemic hypotension. Two phases of induction of the immediate
      early genes were observed. The early phase, peaking at 1-2 h of reperfusion, was
      dominated by marked expression in the dentate gyrus. The second phase, with
      maximal expression at 12-36 h of reperfusion, was observed particularly in the
      vulnerable CA1 and CA3 regions. Hypothermia increased the early induction of one
      of the genes studied, signifying a differential effect of hypothermia upon the
      signal transduction mechanisms activating these genes. The late induction
      occurred earlier after hypothermic than after normothermic ischaemia. The early
      expression of immediate early genes is due to the rapid activation of cytosolic
      response elements caused by the ischaemic insult. We suggest that the late
      induction is a stress signal for activation of repair processes, analogous to the
      cellular response seen after UV light-induced DNA damage. The relatively fast
      induction of the immediate early genes following hypothermic ischaemia may
      reflect a faster resumption of normal intracellular signalling, enhancing
      neuronal recovery.

PMID- 8542059
TI  - pH-dependent facilitation of synaptic transmission by histamine in the CA1 region
      of mouse hippocampus.
AB  - The action of histamine on excitatory synaptic transmission in the CA1 region of
      the mouse hippocampus was investigated. In a medium at pH 7.4 population spikes
      were increased for approximately 60 min after a brief (5 min) perfusion with
      histamine (5 microM) but excitatory postsynaptic potentials (EPSPs) were
      unaffected, as previously reported in the rat. At pH 7.0, however, a late
      component of extra- and intracellularly registered EPSPs was enhanced in two
      phases: a shorter (by 30%) and a longer lasting one (> 1 h by 10%). The NMDA
      antagonist amino-phosphonovalerate (60 microM) blocked this late component and
      prevented the EPSP broadening by histamine. In some cells histamine induced burst
      firing and prolonged EPSPs. The actions on EPSPs were not mediated by any of the
      known histamine receptors as they were not mimicked by histamine H1, H2 and H3
      agonists or blocked by H1, H2 or H3 antagonists. We conclude that histamine
      enhances a late (NMDA) component of hippocampal EPSPs when protonization is
      increased by a slight shift of the pH in the acidic direction. Such shifts occur
      during intense nervous discharges, e.g. in epileptic tissue or following tetanic
      stimulation, and in hypoxic conditions.

PMID- 8542060
TI  - Ectopic substance P and calcitonin gene-related peptide immunoreactive fibres in
      the spinal cord of transgenic mice over-expressing nerve growth factor.
AB  - The aim of this study was to investigate the in vivo effects of CNS over
      expression of nerve growth factor (NGF) on primary sensory neurons. To achieve
      this objective a transgenic mouse model was generated which bore a chick NGF gene
      driven by the myelin basic protein promoter. Northern blot analysis demonstrated
      that high levels of NGF mRNA were detected in the spinal cord of adult transgenic
      mice. Using immunocytochemistry NGF-immunoreactive (IR) oligodendrocytes were
      observed throughout the white matter. Furthermore, numerous ectopic substance P
      (SP)- and calcitonin gene-related peptide (CGRP)-IR fibres were detected in the
      white matter of the spinal cord of transgenic mice. NGF-IR oligodendrocytes and
      ectopic SP- and CGRP- fibres were entirely absent from control mice. In the
      cervical and lumbar dorsal root ganglia, the percentages of SP-IR neurons were
      significantly higher in transgenic mice when compared with controls. At the
      electron microscope level, ectopic SP- and CGRP-IR fibres were characterized as
      unmyelinated axons and axonal boutons. SP colocalized with CGRP in some of those
      axonal boutons and fibres. Capsaicin treatment of adult mice completely abolished
      the ectopic SP-IR fibres, confirming their primary sensory origin. Our results
      indicate that primary sensory neurons are responsive to NGF over-expression in
      the CNS. Ectopic SP- and CGRP-IR fibres in the white matter are likely to
      represent collateral sprouts of the central processes of the dorsal root ganglion
      cells which were triggered by NGF over-expressed in the myelinating
      oligodendrocytes in the spinal cord of transgenic mice.

PMID- 8542061
TI  - Down-regulation of glial glutamate transporters after glutamatergic denervation
      in the rat brain.
AB  - Membrane-localized transporter proteins, expressed in both neurons and glial
      cells, are responsible for removal of extracellular glutamate in the mammalian
      CNS. The amounts and activities of these transporters may be under regulatory
      control. We demonstrate here that cortical lesions, which decrease striatal
      glutamate uptake in synaptosome-containing homogenates by approximately 50%, also
      decrease the striatal concentrations of the astrocytic glutamate transporter
      proteins, GLT-1 and GLAST by approximately 20-30%. Since GABA uptake activity was
      not decreased and glial fibrillary acidic protein was increased in the same
      samples, the lesion-induced losses of GLT-1 and GLAST were not caused by a
      general impairment of neuronal or glial function. The observed reduction in the
      two astrocytic glutamate transporters after corticostriatal nerve terminal
      degeneration indicates that their levels of expression are dependent on
      glutamatergic innervation.

PMID- 8542062
TI  - Differential effects of forebrain 5-hydroxytryptamine depletions on Pavlovian
      aversive conditioning to discrete and contextual stimuli in the rat.
AB  - The experiments examined the effects of depleting forebrain 5-hydroxytryptamine
      (5HT) on Pavlovian aversive conditioning to discrete and contextual stimuli. Rats
      were lesioned with intracerebroventricular injections of the neurotoxin 5,7
      dihydroxytryptamine and then conditioned in a distinctive environment (termed the
      context) to a 30 s auditory stimulus. In 50% of animals the interval between the
      offset of the discrete auditory stimulus and the reinforcer, a mild foot-shock
      (0.5 mA, 0.5 s), was 5 s (the short-trace group) and in the other 50%, 30 s (the
      long-trace group). Theory predicts that animals in the short-trace condition will
      learn more about the discrete stimulus as a predictor of shock and become
      strongly conditioned, while those in the long-trace condition learn relatively
      more about the context. The extent of conditioning to the discrete and contextual
      stimuli was assessed separately, in extinction, using lick-suppression and place
      preference measures respectively. Under these conditions sham subjects exhibited
      the expected dissociation with respect to trace interval. However, lesioned
      animals exhibited a specific impairment in contextual conditioning. The results
      are discussed in terms of the behavioural, neurochemical and neuroanatomical
      specificity of 5HT function in aversive conditioning and the implications for
      general theories of the role of 5HT in aversive processes.

PMID- 8542063
TI  - Interactive events subserving the pupillary light reflex in pigmented and albino
      rats.
AB  - The consensual pupilloconstrictor response requires the intensity information
      that is delivered to each eye to be integrated to produce an averaged response
      such that the pupillary diameter in each eye is equal. Here we have examined how
      luminance information from each eye is integrated in the rat and where the
      integration occurs, using a pupillometry system to record pupillary diameter
      after illumination of one or both eyes. In albino rats the size of the uncrossed
      optic pathway to the pupilloconstrictor centre, the olivary pretectal nucleus, is
      reduced three-fold and there is a concomitant but less dramatic reduction in the
      size of the consensual response. Unilateral lesions of the olivary pretectal
      nucleus in pigmented rats restrict all optic input to the opposite pretectum.
      Stimulation of one or both eyes in these animals suggests that integration occurs
      not only at the level of the olivary pretectal nucleus, but also downstream in
      the Edinger-Westphal nucleus. Parallels with human studies and the opportunity to
      perform secondary lesions suggests the rat may provide a good model in which to
      study the substrates of the pupilloconstrictor response and mechanisms of
      integration of convergent parallel inputs in general.

PMID- 8542064
TI  - Shape and spatial distribution of receptive fields and antagonistic motion
      surrounds in the middle temporal area (V5) of the macaque.
AB  - The spatial organization of receptive fields in the middle temporal (MT) area of
      anaesthetized and paralysed macaque monkeys was studied. In all, 288 neurons were
      successfully recorded. The size and shape of the receptive field (RF) was mapped
      with small patches of translating random dots and the resulting data were fitted
      with a generalized Gaussian. Results show that the RF area increases with
      eccentricity, and is larger in lamina 5 than in other layers. Most of these RFs
      are elongated, and the axis of elongation tends to be orthogonal to the preferred
      direction of motion. The direction selectivity is maintained in all positions in
      the RF, but layer 5 cells are less direction-selective than cells in other
      layers. In a second series of experiments, radial dimensions of the classical RF
      and the antagonistic surround were estimated from area summation tests. These
      data were fitted with the difference of the integrals of two Gaussians. Surrounds
      were weakest in layer 4 and strongest in layer 2. Optimal stimulus diameters,
      also estimated from the area summation curve, were larger in the infragranular
      layers than in the other layers. The maximum sensitivity of the surround was
      clearly displaced from the classical RF (CRF) centre, indicating that the
      surround is not concentric with the CRF. This radial offset and the extent of the
      surround were largest in layers 2 and 5 and smallest in 3a. The extent of the
      surround half-height equalled, on average, 3-4 times that of the CRF. These
      results suggest that antagonistic surrounds are constructed in MT, probably
      through horizontal connections, and that a strong vertical organization exists in
      area MT, as has been shown for V1.

PMID- 8542065
TI  - Native nicotinic acetylcholine receptors in human Imr32 neuroblastoma cells:
      functional, immunological and pharmacological properties.
AB  - IMR32 cells express two classes of surface nicotinic receptors: those labelled
      with high affinity by [125I]neuronal toxin, and those labelled by [125I]alpha
      bungarotoxin. Whole-cell patch-clamp recordings indicate that both classes of
      receptor are able to elicit inward currents that are totally blocked by d
      tubocurarine but only partially blocked by alpha-bungarotoxin. In IMR32 cells,
      nicotine induces an increase in the intracellular level of free Ca2+. This
      increase, which is also completely blocked by d-tubocurarine and only partially
      blocked by alpha-bungarotoxin and Cd2+, is due to extracellular calcium influx
      through both the nicotinic receptors and the voltage-activated Ca2+ channels. By
      using subunit-specific polyclonal antibodies, we have demonstrated that the alpha
      bungarotoxin receptors contain the alpha 7 subunit, but none of the other
      subunits whose transcripts are present in IMR32 cells. The pharmacological
      profile of these human alpha 7-containing alpha-bungarotoxin receptors is similar
      to that observed in the native chick alpha 7 receptor, but there are also some
      species-specific differences.

PMID- 8542066
TI  - The double-ticker: an improved fast drug-application system reveals
      desensitization of the glutamate channel from a closed state.
AB  - The present study describes a modification of the fast drug-application technique
      (ticker) which combines two fast-application systems, 'the double-ticker'. With
      the double-ticker, drugs can be applied to excised patches from either one of the
      tickers permitting switching among three different solutions in the sub
      millisecond range. We made use of this advantageous feature of the double-ticker
      to study two aspects of the glutamate receptor channel in crayfish muscle. The
      first concerns revealing the number of glutamate binding sites from measurements
      of a dose-response relation (2-3 sites). The other relates to the state from
      which the receptor undergoes desensitization. For the quisqualate-sensitive
      glutamate receptor desensitization occurs from a closed state. This is in
      addition to desensitization from an open state.

PMID- 8542067
TI  - Expression of NMDA receptor mRNAs in rat motoneurons is down-regulated after
      axotomy.
AB  - The cytotoxic effects of glutamate via the N-methyl-D-aspartate (NMDA) receptor
      have been suggested to take part in the events leading to death of motoneurons
      after neonatal axotomy. By the use of in situ hybridization and
      immunohistochemistry we have investigated motoneuron mRNA expression of the NMDA
      receptor subunits NR1, NR2B and NR2D and of the NR1 subunit protein in two lesion
      models leading to partial motoneuron death: sciatic nerve transection early
      postnatally in the rat and ventral root avulsion in the adult rat. The results
      were compared with a lesion model with no subsequent death of motoneurons, i.e.
      sciatic nerve transection in the adult rat. All lesions were followed by down
      regulation of the mRNAs for all studied subunits in severed motoneuron
      populations; down-regulation was detectable already at early stages
      postoperatively before any significant death had taken place. The strongest down
      regulation was in fact seen in the lesion with the largest loss of motoneurons
      (ventral root avulsion). The reduction in the expression of NR1 mRNA was
      paralleled by a decrease in NR1 subunit protein. We conclude that down-regulation
      of NMDA receptor subunit expression is part of the acute response to axonal
      injury in motoneurons, whether or not neuronal death follows, and that the
      susceptibility of lesioned motoneurons to excitotoxic effects should be highest
      early after axonal injury.

PMID- 8542068
TI  - A critical period for axon regrowth through a lesion in the developing mammalian
      retina.
AB  - Although the central nervous system of mature mammals is incapable of
      regeneration, certain elements present in the developing system must permit and
      promote the growth of new axons to their initial targets. We investigate whether
      the environment of a developing visual system is capable of supporting
      regeneration in the Brazilian opossum Monodelphis domestica, in which the
      retinofugal system develops postnatally. Retinae were lesioned up to the 16th
      postnatal day and analysed for regeneration after a further 7-10 days.
      Anterograde tracing with Dil showed axons to have regrown from the axotomized
      area of retina directly through the lesion. Retrograde tracing with horseradish
      peroxidase injected into the superior colliculus confirmed that axons from the
      lesioned area of retina had grown to an appropriate position in the midbrain. The
      proportion of retinae in which axonal continuity was restored across the lesion
      decreased as the visual system matured, falling to zero after the 12th postnatal
      day. Thus a critical period exists in the postnatal opossum in which a retinal
      lesion permits axon passage. Correlating these results to the known pattern of
      retinofugal pathway development provides an insight into factors that may
      restrict this critical period to the 12th postnatal day, and suggests that at
      least some of the axotomized neurons are regenerating.

PMID- 8542069
TI  - The critical period for repair of CNS of neonatal opossum (Monodelphis domestica)
      in culture: correlation with development of glial cells, myelin and growth
      inhibitory molecules.
AB  - A comparison was made of neurite growth across spinal cord lesions in the
      isolated central nervous system (CNS) of newborn opossums (Monodelphis domestica)
      at various stages of development. The aim was to define the critical period at
      which growth after injury ceases to occur, with emphasis on growth-inhibitory
      proteins, myelin and glial cells. In postnatal opossums 3-6 days old (P3-6),
      repair was observed 5 days after lesions were made in culture at the cervical
      level (C7) by crushing with forceps. Through-conduction of action potentials was
      re-established and axons stained by Dil grew into and beyond the crush. In a
      series of 66 animals 29 showed repair. In 28 animals at P11-12 with comparable
      lesions repair was observed in five preparations. At P13-14, the CNS was still
      viable in culture, but none of the 25 preparations examined showed any axonal
      growth into the crush or conduction through it. The rostro-caudal gradient of
      development permitted lesions to be made in mature cervical and immature lumbar
      regions of P11-12 spinal cord. Growth across crushes occurred in lumbar but not
      in cervical segments of the same preparation. The development of glial cells and
      myelin was assessed by electron microscopy and by staining with specific
      antibodies (Rip-1 and myelin-associated glycoprotein) in cervical segments of
      neonatal P6-14 opossums. At P8, oligodendrocytes and thin myelin sheaths started
      to appear followed at P9 by astrocytes stained with antibody against glial
      fibrillary acidic protein. By P14, astrocytes, oligodendrocytes and well
      developed myelin sheaths were abundant. The cervical crush sites of P12 cords
      contained occasional astrocytes but no oligodendrocytes. Specific antibodies (IN
      1) to neurite growth-inhibiting proteins (NI-35/250) associated with
      oligodendrocytes and myelin in the rat CNS cross-reacted with opossum proteins.
      Assays using the spreading of 3T3 fibroblasts and IN-1 showed that by P7
      inhibitory proteins became apparent, particularly in the hindbrain and cervical
      spinal cord. The concentrations of NI-35/250 thereafter increased and became
      abundant in the adult opossum. Our finding of a well-defined critical period,
      encompassing only 5 days, in CNS preparations that can be maintained in culture
      offers advantages for analysing mechanisms that promote or prevent CNS repair.

PMID- 8542070
TI  - Epidermal growth factor prevents oxygen-triggered apoptosis and induces sustained
      signalling in cultured rat cerebral cortical neurons.
AB  - Epidermal growth factor (EGF), a conventional mitogenic factor, acts as a
      neurotrophic factor on several types of neurons in the central nervous system. We
      found that EGF prevented the death of rat cerebral cortical neurons cultured in a
      50% oxygen atmosphere. This high-oxygen-triggered cell death showed features of
      apoptotic cell death, which was blocked by inhibitors of RNA or protein
      synthesis. EGF prevented the oxygen-induced death of the cultured cortical
      neurons in a dose-dependent manner. Basic fibroblast growth factor (bFGF) also
      prevented this cell death, although there was no apparent additive effect of EGF
      and bFGF. Among the cultured cortical neurons, we observed neurons possessing the
      EGF receptor and cells expressing c-Fos protein in response to EGF. The cortical
      neurons were cultured in the presence of cytosine arabinoside, and the number of
      glial fibrillary acidic protein-positive astroglial cells was < 0.5% of that of
      the corresponding microtubule-associated protein 2-positive neurons. Therefore,
      the effect of EGF on the cultured cortical neurons is thought to be due to a
      direct action. We also examined EGF-induced signalling in the cultured cortical
      neurons. We found that EGF induced the sustained tyrosine phosphorylation of the
      EGF receptor and sustained the activation of mitogen-activated protein kinase in
      the cultured cortical neurons. We suggest that EGF may exert the survival effect
      through the prolonged activation of the EGF signalling.

PMID- 8542071
TI  - Areal differences of NPY mRNA-expressing neurons are established in the late
      postnatal rat visual cortex in vivo, but not in organotypic cultures.
AB  - In order to learn about the factors regulating the postnatal development of
      neocortical peptidergic neuron populations, we have analysed neurons expressing
      neuropeptide Y (NPY) by immunohistochemistry and in situ hybridization in
      developing and adult rat visual cortical areas 17 and 18a in vivo, and in
      organotypic slice cultures of rat visual cortex. For quantitative analysis, the
      percentage of NPY mRNA-expressing neurons was determined in supragranular layers
      I-IV, in infragranular layers V and VI and in the white matter. In vivo, this
      percentage increased in visual areas 17 and 18a until postnatal day 21 in supra-
      and infragranular layers. Initially, in both areas the neurons were about equally
      distributed in supra- and infragranular layers (a ratio of 1:1). During the
      second postnatal month, the percentage of NPY mRNA-expressing neurons in area 18a
      declined by approximately 50% in both supra- and infragranular layers, so that
      the ratio of 1:1 remained constant. In contrast, in area 17 the percentage of
      neurons in supragranular layers remained fairly constant, but it declined to 50%
      in infragranular layers, so that by postnatal day 70 the ratio was gradually
      shifted to 2:1. Throughout development, area 18a contained significantly more NPY
      mRNA-expressing neurons than area 17. In organotypic slice cultures, a high
      density of NPY mRNA-expressing neurons had appeared by 10 days in vitro. A much
      higher percentage of neurons expressed NPY mRNA. The ratio of labelled neurons in
      supra- versus infragranular layers was 1:1. Both ratio and percentage remained
      constant from 10-85 days in vitro. The decline in vivo was not caused by an
      elimination of transient cell types. All cell types persisted into adulthood.
      Four NPY peptide-immunoreactive neuronal types were classified by axonal
      morphology in organotypic slice cultures and in vivo; they include (i) cells in
      layer VI/white matter with horizontal axons and ascending collaterals, (ii) cells
      in layers V/VI with descending axon and horizontal collaterals, (iii) Martinotti
      cells in layers V/VI with ascending axons, and (iv) cells in layers III-V with
      columnar axons. Two further types, bipolar cells with axons descending from
      dendrites and small basket cells with short horizontal axons, both found in vivo
      in layers II/III, could not be unequivocally identified in organotypic slice
      cultures. The NPY-immunoreactive neuron types had already formed a dense
      innervation of the cultures by 10 days in vitro, which remained stable for up to
      85 days in vitro, and resembled the innervation observed in vivo. NPY peptide
      immunoreactive neurons in organotypic slice cultures and in vivo were distributed
      in cortical layers II/III, V and VI and the white matter, but rarely in layers I
      and IV, which corresponded to the distribution of NPY mRNA-expressing neurons.
      However, with in situ hybridization more neurons were detectable, especially in
      layers II/III. A majority of NPY mRNA-expressing neurons co-localized NPY
      peptide, somatostatin and calbindin. We conclude that intrinsic cues were
      sufficient to drive the molecular expression of the NPY phenotype, the
      morphological differentiation and the stabilization of an organotypic NPY
      innervation in organotypic slice cultures. However, the area- and lamina-specific
      changes observed in vivo were not observed under monoculture conditions.

PMID- 8542072
TI  - Activation of p44 and p42 MAP kinases is not essential for the survival of rat
      sympathetic neurons.
AB  - We have examined whether activation of MAP kinases [or extracellular signal
      regulated kinases (ERKs)] is required for the survival of rat sympathetic neurons
      by comparing the actions of three survival factors whose survival-promoting
      actions can be blocked by neutralizing Fab fragments to p21 ras (Nobes and
      Tolkovsky, 1995, Eur. J. Neurosci., 7, 344-350), nerve growth factor (NGF), the
      cytokines ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor
      (LIF), and the cyclic AMP analogue 4-(8-chlorophenylthio)cAMP (CPTcAMP). NGF
      induced survival was accompanied by an intense (15- to 30-fold) and steady (> 24
      h) activation of p44 and p42 ERKs which waned rapidly (t1/2 approximately 30 min)
      upon NGF withdrawal. However, concentrations of NGF that induced a weak (4- to 5
      fold) stimulation of the ERKs were not sufficient to maintain long-term survival.
      Moreover, prolonged and intense stimulation of the ERKs by NGF for up to 15.5 h
      was unable to confer long-term survival, since withdrawal of NGF after this time
      resulted in neuronal death that was kinetically indistinguishable from the death
      of neurons that had not been exposed to NGF. By contrast, CNTF and LIF continued
      to support survival for up to 3 days after eliciting only transient (< 30 min and
      1 h respectively) activation of p44 and p42 ERKs, while CPTcAMP induced survival
      for several days without any measurable activation of the ERKs. Taken together,
      these data suggest that ERK activation per se is neither necessary nor sufficient
      for survival and that alternative pathways exist for effecting long-term survival
      of rat sympathetic neurons.

PMID- 8542073
TI  - Synaptic input of horizontal interneurons in stratum oriens of the hippocampal
      CA1 subfield: structural basis of feed-back activation.
AB  - The synaptic input of interneurons with horizontal dendrites in stratum oriens of
      the CA1 region was investigated, with particular attention to the portion of
      synapses originating from local pyramidal cells. Most of these GABAergic
      interneurons are known to contain somatostatin, and terminate on pyramidal
      dendrites in conjunction with entorhinal afferents in stratum lacunosum
      moleculare. A smaller number of horizontal cells in this layer are immunoreactive
      for calbindin, and project to the medial septum. Selective ischaemic degeneration
      was used to label local axon collaterals of CA1 pyramidal cells, and
      immunostaining for mGluR1 or calbindin to visualise somatostatin- and calbindin
      containing horizontal interneurons, respectively, at the stratum oriens-alveus
      border. The number of degenerating and intact synaptic boutons was counted on
      mGluR1- as well as on calbindin-positive dendrites and somata, whereas in another
      group of animals the proportion of GABA-immunoreactive synapses was estimated on
      calbindin-positive dendrites. On average, > 60% of the total presynaptic elements
      of both cell types were degenerating, i.e. originated from CA1 pyramidal cells,
      whereas GABA-positive boutons, which are known to survive ischaemia, are likely
      to account for a large proportion of non-degenerating boutons. Thus the vast
      majority of presumed excitatory synapses on somatostatin- and calbindin
      containing horizontal neurons derives from local collaterals of CA1 pyramidal
      cells. The remaining GABA-negative synapses surviving ischaemia may also
      originate from CA1 pyramidal cells, e.g. from those in the ventral hippocampus,
      which are rarely damaged by global forebrain ischaemia. Alternative sources may
      include subcortical afferents known to innervate interneurons, or ipsi- and
      contralateral CA3 pyramidal cells, which, according to the present results, may
      account only for a negligible number of synapses on these interneurons types. We
      conclude that somatostatin-containing neurons at the oriens-alveus border of CA1,
      which are likely to mediate an inhibitory control of the efficacy and/or
      plasticity of entorhinal synapses on pyramidal cell dendrites, are driven
      primarily in a feed-back manner. The source of afferent excitation for calbindin
      containing horizontal neurons in this region is very similar, suggesting that the
      GABAergic hippocamposeptal feed-back is also activated by local pyramidal cell
      collaterals.

PMID- 8542074
TI  - Characterization of shock-induced action potential extension during acute
      regional ischemia in rabbit hearts.
AB  - INTRODUCTION: Defibrillation shocks produce extension of the myocardial action
      potential repolarization time (AP extension) in nonischemic myocardium. AP
      extension may synchronize repolarization in the heart because the extension
      increases when shock timing is increased. We tested whether AP extension occurs
      and whether it increases when shock timing is increased in regionally ischemic
      isolated perfused rabbit hearts stained with the transmembrane voltage sensitive
      fluorescent dye, di-4-ANEPPS and given diacetyl monoxime to eliminate motion
      artifacts. METHODS AND RESULTS: Before and after left anterior descending (LAD)
      coronary artery occlusion, APs were recorded on the anterior left ventricular
      epicardium with an epifluorescence measurement system. Hearts were paced with a
      train of 10 stimuli (S1) and then during the 10th AP were given a defibrillation
      shock (S2) from epicardial electrodes on either side of the recording region.
      Before LAD occlusion, duration of the 9th S1-induced AP measured at full
      repolarization was 171 +/- 11 msec (mean +/- SD). Within 15 minutes after LAD
      occlusion, the AP duration became shorter (P < 0.05) and more variable (137 +/-
      47 msec), and APs with negligible plateaus were observed. Extension of the 10th
      AP by S2 was significant both before (mean extension of 59 to 65 msec for three
      S2 waveforms tested) and after LAD occlusion (mean extension of 35 to 41 msec).
      Unlike the results before LAD occlusion, AP extension after occlusion was
      independent of absolute shock timing expressed in msec. When timing was expressed
      as a fraction of individual AP durations, AP extension after occlusion increased
      with increases in shock timing. CONCLUSIONS: Shocks extend APs during ischemia;
      however, absolute time dependence of AP extension is not constant among cells
      that have different AP durations during ischemia. This may influence postshock
      repolarization synchrony when different AP durations exist in different parts of
      regionally ischemic hearts.

PMID- 8542075
TI  - Slowly recovering cardiac sodium current in rat ventricular myocytes: effects of
      conditioning duration and recovery potential.
AB  - INTRODUCTION: Recovery of the Na channel from inactivation is essential to the
      normal conduction and refractoriness of the myocardium. In addition to fast
      recovery, occurring within several milliseconds at hyperpolarized potentials, a
      component of the current exhibits slow recovery occurring over hundreds of
      milliseconds. Long conditioning depolarizations potentiate slow recovery. METHODS
      AND RESULTS: This study was designed to test conditioning durations (tc) between
      0.25 and 4 seconds (s) as to whether recovery was slowed by an effect on the fast
      (tau f) and slow (tau s) time constants of recovery, the relative amplitude of
      the slow component (As), or both. We studied Na channel recovery at -150 mV from
      inactivation using whole cell voltage clamp of rat ventricular cells at 23
      degrees C using a two-pulse recovery protocol. Longer conditioning durations
      dramatically increased A2 (from 12% for tc = 500 msec to 37% for tc = 4000 msec,
      P < 0.01). Neither tau f (6 vs 5 msec) nor tau s (115 vs 140 msec) were
      significantly affected. In a second set of experiments, the recovery potential
      was depolarized to a potential at which the sodium current was 70% available
      (approximately equal to - 105 mV). This recovery potential had no significant
      effect on A2, but both tau f and tau s were significantly slower (e.g., at tc = 2
      s, tau s = 147 msec and As = 28% at Vr = - 150 mV, and tau s = 456 msec and As =
      29% at Vr approximately equal to - 105 mV). In addition, a 1- to 2-msec lag in
      the onset of recovery was prominent at the depolarized recovery potentials.
      CONCLUSIONS: Our results support a model for slow recovery where conditioning
      duration determines entry into an inactivated state from which Na channels
      recover slowly, and recovery potential determines the rate of recovery from this
      state. A kinetic scheme with at least three inactivated states is proposed. These
      results also have implications for cardiac excitability under conditions, such as
      ischemia, where membranes are depolarized.

PMID- 8542076
TI  - Role of calcium loading in early afterdepolarizations generated by Cs+ in canine
      and guinea pig Purkinje fibers.
AB  - INTRODUCTION: Our previous observations indicate that the Na+:Ca2+ exchange
      current (INa:Ca) plays an important role in early afterdepolarizations occurring
      at more negative Vm (L-EAD). The purpose of these studies was to examine the role
      of Ca(2+)-loading, which stimulates INa:Ca, in generation of L-EAD. METHODS AND
      RESULTS: Purkinje strands and preparations of ventricular myocardium from dogs
      and guinea pigs were superfused with oxygenated physiologic buffer solutions at
      37 degrees C. To induce EADs, [K+]o was reduced to 2.0 to 3.0 mM and [Cs+]o (3.6
      to 4.0 mM) was added at slow rates of < or = 0.3 Hz. Isometric contraction in
      canine Purkinje strands and guinea pig papillary muscles doubled in 1-hour
      exposure to Cs+ and low [K+]o at slow rates and the uptake of 45Ca2+ was
      approximately doubled after 30 minutes. Forty-three percent of Purkinje fibers
      developed L-EAD after a latent period of 17 to 123 minutes of exposure. Ouabain
      (0.2 microM) suppressed L-EAD within 10 minutes reversibly. Ca(2+)-loading (low
      [Na+]o or high [Ca2+]o) for 5 to 10 minutes before exposure to Cs+, low [K+]o,
      and slow rates resulted in rapid development of L-EAD in all preparations during
      subsequent exposure. In Ca(2+)-loaded preparations, delayed afterdepolarizations
      (DADs) as well as L-EADs developed. CONCLUSIONS: Reduction of K+ currents with
      Cs+, low [K+]o, and slow rates induced L-EAD in a fraction of Purkinje fibers
      after a latent period during which Ca(2+)-loading of the sarcoplasmic reticulum
      occurred, while fibers preloaded with Ca2+ developed L-EAD rapidly and uniformly.
      These findings indicate that Ca(2+)-loading is a critical condition for the
      development of L-EAD. Early suppression of L-EAD by ouabian suggests a dependence
      of L-EAD on low [Na+]i. These findings implicate INa:Ca in the generation of L
      EAD.

PMID- 8542077
TI  - Gap junction protein phenotypes of the human heart and conduction system.
AB  - INTRODUCTION: Gap junction channels are major determinants of intercellular
      resistance to current flow between cardiac myocytes. Alterations in gap junctions
      may contribute to development of arrhythmia substrates in patients. However,
      there is significant interspecies variation in the types and amounts of gap
      junction subunit proteins (connexins) expressed in disparate regions of mammalian
      hearts. To elucidate determinants of conduction properties in the human heart, we
      characterized connexin phenotypes of specific human cardiac tissues with
      different conduction properties. METHODS AND RESULTS: The distribution and
      relative abundance of Cx37, Cx40, Cx43, Cx45, and Cx46 were studied
      immunohistochemically using monospecific antibodies and frozen sections of the
      sinoatrial node and adjacent atria. AV node and His bundle, the bundle branches,
      and the left and right ventricular walls. Patterns of expression of these
      connexins in the human heart differed from those in previous animal studies.
      Sinus node gap junctions were small and sparse and contained Cx45 and apparently
      smaller amounts of Cx40 but no Cx43. AV node gap junctions were also small and
      contained mainly Cx45 and Cx40 but, unlike the sinus node, also expressed Cx43.
      Atrial gap junctions were larger than nodal junctions and contained moderate
      amounts of Cx40, Cx43, and Cx45. Junctions in the bundle branches were the
      largest in size and contained abundant amounts of Cx40, Cx43, and Cx45. Gap
      junctions in ventricular myocardium contained mainly Cx43 and Cx45; only a very
      small and amount of ventricular Cx40 was detected in subendocardial myocyte
      junctions and endothelial cells of small to medium sized intramural coronary
      arteries. Minimal Cx37 and Cx46 immunoreactivity was detected between occasional
      atrial or ventricular myocytes. CONCLUSIONS: The relative amounts of individual
      connexins and the number and size of gap junctions vary greatly in specific
      regions of the human heart with different conduction properties. These
      differences likely play a role in regulating cardiac conduction velocity.
      Differences in the connexin phenotypes of specific regions of the human heart and
      experimental animal hearts must be considered in future experimental or modeling
      studies of cardiac conduction.

PMID- 8542078
TI  - Intermittent preexcitation and mesothelioma of the atrioventricular node: a
      hitherto undescribed entity.
AB  - This is the first documented case of spontaneous intermittent preexcitation
      associated with mesothelioma of the atrioventricular (AV) node. A 66-year-old
      male with recurrent atrial arrhythmias, palpitations, heart failure, and marked
      intra-atrial conduction defect that required a pacemaker died during sleep.
      Electrophysiologic study revealed left free-wall bypass tract with marked intra
      atrial conduction defect and prolonged conduction across the bypass tract. With
      atrial pacing, high degrees of block were noted in the bypass tract. Serial
      section of the conduction system and both AV rims revealed two left posterior and
      lateral bypass pathways with patchy areas of fibrosis. A large mesothelioma
      (benign AV nodal tumor) almost completely replaced the AV node. In addition,
      there was marked fatty infiltration of the atria. In summary: (1) the
      intermittent preexcitation with prolonged conduction across the bypass tract and
      block with atrial pacing were probably related to the incomplete patchy
      degenerative changes in the bypass tract, and/or almost complete replacement of
      the AV node by the tumor; (2) the intra-atrial conduction defect was probably
      related to the replacement of the AV node by mesothelioma and/or the fatty
      infiltration of the atria; and (3) the paroxysmal atrial arrhythmias probably
      reflect the marked atrial pathology.

PMID- 8542079
TI  - Benefits and lessons learned from stored electrogram information in implantable
      defibrillators.
AB  - Implantable defibrillators have evolved from simple event counters to
      sophisticated diagnostic monitoring units capable of storing electrocardiographic
      information surrounding arrhythmia events and device therapy. In this review, the
      nature and characteristics of these stored electrocardiographic recordings are
      discussed and examples displayed. Potential benefits and limitation of stored
      electrogram analysis are described with respect to both clinical utility and the
      ability to enhance our understanding of ventricular arrhythmogenesis. Finally,
      future developments to improve data storage, retrieval, and analysis are
      identified.

PMID- 8542080
TI  - Future ablation concepts of tachyarrhythmias.
AB  - Application of radiofrequency energy to arrhythmogenic substrates after careful
      cardiac mapping could ensure a high success rate in eliminating certain types of
      tachyarrhythmias. Future studies of catheter ablation will focus on how to
      improve ablation efficacy and achieve a better result in various types of
      tachyarrhythmias. More information about the arrhythmogenic mechanisms will be
      provided to improve the knowledge of diagnostic and interventional
      electrophysiology.

PMID- 8542081
TI  - What is the tachycardia mechanism?

PMID- 8542082
TI  - Gastric remnant carcinoma after partial gastrectomy for benign and malignant
      gastric lesions.
AB  - BACKGROUND: A retrospective study was designed to evaluate the clinicopathologic
      characteristics and prognosis of gastric stump carcinoma (GSC) after gastrectomy
      for gastric adenocarcinoma. STUDY DESIGN: A comparison of the clinicopathologic
      features was made between 12 cases of GSC and 27 cases of remnant carcinoma (RC)
      following gastrectomy for adenocarcinoma. The various factors influencing
      survival of both groups of patients were evaluated separately and by multivariate
      analysis. RESULTS: Gastric stump carcinoma emerges late after initial gastrectomy
      and has a significant tendency toward lymph node metastasis. No difference was
      observed between the survival curves for patients with GSC or RC after
      gastrectomy for malignancy. Serosal invasion was the factor most affecting
      survival. CONCLUSIONS: Early diagnosis is most important for management of the
      disease, and only patients with T2 staged GSC according to the Union
      Internationale Contre le Cancer classification system might benefit from
      extensive lymphadenectomies.

PMID- 8542083
TI  - The role of the spleen, platelets, and plasma hepatocyte growth factor activity
      on hepatic regeneration in rats.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a humoral factor that may act as a
      trigger for hepatic regeneration. In this study, changes in the plasma HGF
      activity on hepatic regeneration in a splenectomized condition were measured for
      the first time, while the role of the spleen and platelets on hepatic
      regeneration were also carefully evaluated. STUDY DESIGN: Seventy-five male
      Wistar rats were classified into three groups: group A consisted of rats who
      underwent a sham operation and a partial hepatectomy; group B consisted of those
      who underwent a splenectomy and partial hepatectomy; and group C consisted of
      those who underwent a splenectomy, partial hepatectomy, and were administered an
      antiplatelet agent. RESULTS: At 24 hours after partial hepatectomy, the weights
      of the livers of the rats in groups B and C were significantly greater than those
      of group A, while the labeling index of group C was significantly higher than
      that of group A and also tended to be higher than that of group B. Regarding the
      number of platelets, the transient increase in group A occurred earlier than that
      of either group B or C. The plasma HGF activities also showed a transient
      increase and the maximum levels were reached at 24 hours in group A, six hours in
      group B, and 12 hours in group C. CONCLUSIONS: It is suggested that the spleen
      plays an inhibitory role in hepatic regeneration. In the early stage of hepatic
      regeneration, platelets possibly control HGF induction, while in the following
      stage, a possible feedback mechanism is also postulated to exist.

PMID- 8542084
TI  - Pedestrian-motor vehicle trauma: an analysis of injury profiles by age.
AB  - BACKGROUND: Pedestrian-motor vehicle trauma (PMVT) is a common mechanism of
      injury in urban populations. STUDY DESIGN: We performed a retrospective review of
      273 PMVT victims (16 percent of all patients with blunt injuries) seen at a Level
      I trauma center over a three-year period. Patients were analyzed by age and
      grouped as children (age younger than 16 years), adults (age 16 to 59 years), or
      elderly (age older than 59 years). RESULTS: Children constituted 27 percent of
      the patients, adults 54 percent, and elderly 19 percent. This mixture had
      significantly more children and elderly than the population at large or the
      entire blunt trauma population at our hospital. The majority of patients (66
      percent) were male, with females outnumbering males only in the elderly group.
      Elderly patients were more frequently admitted to the intensive care unit (ICU)
      and had significantly longer ICU and hospital stays. Injury Severity Scores were
      successively higher in each age group and significantly higher in the elderly.
      Extremity trauma was most common in all three groups, followed by head injuries.
      The elderly patients were more prone to chest and pelvic injuries and the
      children most often had femur fractures. Operations were performed in 22 percent
      of the patients; orthopedic procedures were most frequent. The mortality rate was
      6 percent, with 69 percent of the deaths occurring during the initial
      resuscitation efforts. The mortality rate was significantly higher in the elderly
      patients (13 percent). The majority of accidents occurred during nighttime hours,
      especially in the adult group. Half of the accidents occurred on the weekend,
      with the greatest number on Saturday. One-third of the accidents occurred during
      the months of October to December. CONCLUSIONS: Pedestrian-motor vehicle trauma
      is a common injury, with distinct epidemiological features that may be useful in
      accident prevention strategies.

PMID- 8542085
TI  - Usefulness of Japanese staging in the prognosis of patients treated operatively
      for adenocarcinoma of the head of the pancreas.
AB  - BACKGROUND: Differences in the clinical staging in Japan from that of the Union
      Internationale Contre le Cancer (UICC) staging system may account for
      discrepancies in the prognosis of carcinoma of the pancreas between Japan and the
      United States of America. STUDY DESIGN: This study compares the usefulness of
      Japanese staging with the UICC staging in 1,689 patients who underwent resection
      for carcinoma of the pancreatic head registered with the Japan Pancreas Society.
      RESULTS: The survival rate was correlated with the Japanese stage classification.
      The survival rate of patients with T4 tumors was surprisingly better than for
      those with T2 or T3 tumors. The extent of lymph node involvement and of
      extrapancreatic tissue invasion reflected the prognosis. The UICC staging system
      did not reflect differences in prognosis among the four stages, especially
      between stages II and III. CONCLUSIONS: To establish a more practical and
      universal staging system for carcinoma of the pancreas, the Japanese system may
      offer improvements in predicting the prognosis of American or European patients
      with this disease.

PMID- 8542086
TI  - Endogenous endophthalmitis associated with pyogenic hepatic abscess.
AB  - BACKGROUND: Endogenous endophthalmitis has been associated with pyogenic hepatic
      abscess in several recent anecdotal reports. The purpose of this study was to
      determine the incidence of endophthalmitis associated with pyogenic hepatic
      abscess, identify the degree of association with Klebsiella pneumoniae as a
      causative organism, and determine the outcome of treatment. STUDY DESIGN: A
      retrospective study was performed of 352 consecutive patients with a clinical
      diagnosis of pyogenic hepatic abscess who had been admitted to Chang Gung
      Memorial Hospital in Kaohsiung between 1986 and 1993. Findings from complete
      ophthalmologic evaluations and treatment results were recorded. RESULTS: Eleven
      patients (3.1 percent) with endogenous endophthalmitis (monocular in eight and
      binocular in three) were found among the 352 cases of pyogenic hepatic abscess.
      Seven of the patients had diabetes mellitus and their blood glucose was poorly
      controlled. Only one patient had an intrahepatic stone as the cause of hepatic
      abscess, the other abscesses were of cryptogenic origin. The causative organism
      was mainly K. pneumoniae and the diagnosis was made by blood culture in ten
      patients, hepatic aspirate culture in seven, and vitreous contents culture in
      three. Systemic antibiotics were given in all patients with endogenous
      endophthalmitis. Percutaneous catheter drainage for hepatic abscess under echo
      guidance was performed in seven patients, medical treatment only was performed in
      three patients, and percutaneous tapping of abscess was done in one patient. All
      11 patients were alive at the time of writing. Intravitreous culture followed by
      injection of antibiotics and steroids was immediately undertaken if septic
      endophthalmitis was suspected, except in two patients, who lost vision before any
      treatment was given. In five patients, cefamezin and gentamicin were given, and
      in four patients vancomycin, amikacin, and dexamethasone were given every three
      days if necessary. Finally, among the total of 14 eyes, there was blindness in
      ten, three of these had no light perception initially. In seven patients there
      had been a delay of treatment longer than one day. In one eye there was "counting
      fingers" vision and in three eyes there remained some vision. CONCLUSIONS:
      Physicians should be alert to the development of endogenous endophthalmitis when
      a patient with pyogenic hepatic abscess or bacteremia complains of ocular
      symptoms. Prompt diagnosis and vigorous treatment with intravitreous injections
      of vancomycin, amikacin, and dexamethasone within 24 hours can save the patient's
      eyes and vision.

PMID- 8542087
TI  - Practical classification of the branching types of the biliary tree: an analysis
      of 1,094 consecutive direct cholangiograms.
AB  - BACKGROUND: The structure of the biliary tree has been classified according to
      the relationship between the hepatic segmental ducts and the cystic duct. Because
      laparoscopic cholecystectomy demands precise knowledge of biliary anatomy, we
      propose a simplified classification of the bile ducts. STUDY DESIGN: A
      consecutive series of 1,094 direct cholangiograms were analyzed and the letters
      A, P, R, L, and C were designated for the right anterior, right posterior, right,
      left, and cystic ducts, respectively. The arborizing patterns of the hepatic bile
      ducts were classified into either the bifurcation of the right and left ducts
      (RL); triple confluence of the right anterior, right posterior, and left ducts
      (APL); separate branching of A and P in the duodenohepatic direction; or discrete
      branching of P and A (P-AL) where branches A and P were in reverse of A-PL.
      Cystic duct anomaly was added in parentheses. RESULTS: The classified ducts had
      the following distribution: RL, 67.7 percent; APL, 17.7 percent; A-PL, 8.0
      percent; and P-AL, 6.0 percent. Cystic duct anomalies occurred in 1.6 percent of
      all the cases and were in frequent association with the P-AL pattern. The most
      common type was P-AL (P-C) seen in 0.5 percent of cases, where the cystic duct
      merged into the lower branching P. CONCLUSIONS: Our practical classification of
      the biliary tree anatomy may contribute to the practice of biliary surgery.

PMID- 8542088
TI  - Measurement of gap length in esophageal atresia: a simple predictor of outcome.
AB  - BACKGROUND: Previous classifications of esophageal atresia (EA) and
      tracheoesophageal fistula (TEF) have concentrated on associated medical
      conditions that influence survival. We propose a classification based on gap
      lengths to define the magnitude of the surgical problems in EA and TEF and
      correlate them with outcome. STUDY DESIGN: Gaps between the esophageal ends were
      classified as long (greater than 3 cm), intermediate (greater than 1 cm but less
      than or equal to 3 cm) or short (less than or equal to 1 cm). A series of 66
      consecutive patients with EA and TEF were studied. RESULTS: The outcomes of
      patients with long (n = 16), intermediate (n = 16), and short (n = 34) gaps were
      respectively: death (18 percent, 6 percent, 3 percent), anastomotic leak (31
      percent, 25 percent, 6 percent), stricture (44 percent, 31 percent, 17 percent),
      recurrent TEF (6 percent, 6 percent, 6 percent), gastroesophageal reflux (56
      percent, 37 percent, 36 percent), and failure to thrive (56 percent, 43 percent,
      18 percent). The mean hospital stay at first admission was (97, 54, 24 days,
      respectively) and the mean number of readmissions was (6.9, 5.2, 3.4,
      respectively). CONCLUSIONS: This classification, which is based on easily
      measurable criteria, provides a useful method to predict morbidity, long-term
      outcome, and health costs associated with EA and TEF surgery.

PMID- 8542089
TI  - A comparison of the strength of knots tied by hand and at laparoscopy.
AB  - BACKGROUND: The strength of knots tied at laparoscopy was compared with that of
      hand-tied knots. STUDY DESIGN: The force needed to undo or break eight types of
      knots that were tied in fresh postmortem human stomachs was measured. The
      knotting performance of nylon, polyglactin 910, braided silk,
      polytetrafluoroethylene, braided polyester fiber, braided polyester suture,
      polyamide 66, and polydiaxone was also compared. RESULTS: Measurements of knot
      strength of two to six half hitches (hand tied) showed that four half hitches
      were necessary to tie a secure nonslipping knot with most monofilament threads
      (nylon, polytetrafluoroethylene, braided polyester suture, and polyamide 66),
      while three half hitches were adequate to secure a knot when polyglactin 910,
      braided polyester fiber, silk, and polydiaxone were used. Additional throws did
      not increase knot strength once the knot no longer slipped (p = NS). Some
      commonly tied knots, three half hitches and surgical knots at laparoscopy were
      weaker than the same hand-tied knots (p < 0.05) but an additional throw increased
      knot security (p < 0.01). Differences between laparoscopic and hand-tied knot
      strengths were greater for monofilament than multifilament threads. There was a
      wider distribution of strengths for laparoscopically tied than hand-tied knots.
      Four half hitches were the most secure configuration for laparoscopically tied
      knots and were significantly stronger than three half hitches and surgical knots
      (p < 0.01). The extracorporeally tied slipknot (Roeder loop) was significantly
      less secure than four half hitches (p < 0.05). CONCLUSIONS: This study
      demonstrates that laparoscopically formed knots may be weaker than those tied by
      hand and shows that improvements in knot strength at laparoscopy can be achieved
      by choice of optimal knot configuration for different suture materials.

PMID- 8542090
TI  - Overexpression of c-myc messenger RNA in primary and metastatic lesions of
      carcinoma of the stomach.
AB  - BACKGROUND: Although c-myc expression in carcinoma of the stomach has been
      reported to be involved in progression of the disease, little is known about the
      mechanism or significance of its expression. STUDY DESIGN: We measured c-myc
      messenger RNA (mRNA) levels by Northern blot hybridization in 51 primary gastric
      carcinoma lesions and 15 metastatic lesions accompanied by normal mucosal tissues
      from the same patients. The extent of c-myc mRNA expression in malignant lesions
      was determined and compared with that in normal mucosal tissues. The clinical and
      pathologic significance of c-myc mRNA expression was investigated. RESULTS: In 35
      (68.6 percent) of 51 primary gastric carcinomas c-myc mRNA was overexpressed.
      Expression was found to be more frequent and stronger in early lesions than in
      advanced lesions (90 percent, 6.15-fold compared with 54.8 percent, 2.42-fold, p
      < 0.05). However, c-myc mRNA expression in the primary lesions showed little
      influence on either the histologic features or the disease progression. C-myc
      mRNA levels were higher in every metastatic lesion than in the primary lesions
      (9.89-fold compared with 3.04-fold, p < 0.05). CONCLUSIONS: These observations
      suggest that c-myc mRNA overexpression may play a role in the early development
      of primary lesions as well as in the formation of metastatic lesions of
      carcinomas of the stomach.

PMID- 8542091
TI  - Richter's hernia--a surgical pitfall.
AB  - BACKGROUND: Although Richter's hernia was first described in 1598, little
      attention has been given to this topic in recent literature. The diagnosis of
      Richter's hernia is difficult because of the innocuous development of signs and
      symptoms and it is associated with a high mortality rate. Awareness of this
      relatively rare surgical entity is important. STUDY DESIGN: Of 350 patients with
      incarcerated hernias who underwent operation between 1977 and 1994 at the
      Department of Surgery "A," Assaf Harofeh Medical Center, 14 had strangulated
      Richter's hernia. A retrospective study was carried out in order to characterize
      the clinical manifestations of Richter's hernia and to assess preoperative delay,
      hospital stay, and complication and mortality rates. A comparison study was made
      with matched patients with strangulated hernias of non-Richter's type.
      Differences in morbidity and mortality rates, preoperative delay, and hospital
      stay of patients with Richter's hernias and the comparison group were evaluated.
      RESULTS: Of 14 patients with Richter's hernia, seven underwent intestinal
      resection. The hernia most commonly occurred at the femoral and inguinal sites.
      Compared with patients with other hernias, patients with Richter's hernias had
      greater preoperative delay, rate of bowel resection, length of hospital stay, and
      postoperative morbidity and mortality rates. CONCLUSIONS: Early operative
      intervention is the mainstay of successful management of Richter's hernia and
      awareness of this disease and its misleading clinical presentation is of utmost
      importance.

PMID- 8542092
TI  - Splenic venous hypertension presenting as variceal hemorrhage caused by portal
      hypertension.
AB  - BACKGROUND: Splenic venous hypertension (SVH) may cause variceal hemorrhage that
      is clinically indistinguishable from similar bleeding caused by portal
      hypertension (PH). This may lead to erroneous treatment, including inappropriate
      portosystemic shunt placement. STUDY DESIGN: A retrospective review of 58 cases
      of variceal hemorrhage referred for transmesenteric variceal sclerotherapy and
      transvenous intrahepatic portosystemic shunt (TIPS) placement revealed that seven
      patients had SVH as a cause of bleeding, and required treatment other than TIPS.
      The role of medical imaging in the diagnosis and management of SVH was analyzed.
      RESULTS: Clinical data did not permit a differential diagnosis between PH and SVH
      as the cause of bleeding in all cases. Splenic venous hypertension was suspected
      and then confirmed exclusively by contrast-enhanced computed tomography (CT) and
      angiography, which are essential for correct patient management. CONCLUSIONS:
      Computed tomography should be routinely performed to exclude SVH before TIPS
      placement. In instances in which CT fails to establish the diagnosis or splenic
      artery occlusion is considered for patient management, angiography may be used.

PMID- 8542093
TI  - An alternative technique to create end-of-vein to side-of-artery fistula for
      angioaccess.

PMID- 8542094
TI  - Necrotizing soft tissue infections: obstacles in diagnosis.
AB  - BACKGROUND: This study was done to identify obstacles in the early diagnosis and
      treatment of necrotizing soft tissue infections. STUDY DESIGN: A ten-year
      retrospective case series was analyzed. RESULTS: Data from 29 patients were
      analyzed. Among patients undergoing early operation within 24 hours of admission
      (n = 17) there was one death (6 percent mortality rate); survivors averaged 2.9
      operations per patient. By comparison, of patients with delayed operation (n =
      12) three died (25 percent mortality rate) and there were 3.6 operations per
      patients. Positive fine-needle aspiration (FNA) of suspicious lesions,
      demonstrating either pus or bacteria by Gram's stain, led to early operation in
      80 percent of patients tested. Patients with soft tissue gas on radiographs were
      more likely to undergo early operation (58 percent). Delayed operation was more
      common in the absence of radiographic findings. All patients admitted to
      nonsurgical services had delayed operations. CONCLUSIONS: Suspected necrotizing
      soft tissue infections require prompt surgical evaluation and early operative
      exploration. Early operation with definitive surgical therapy initiated within 24
      hours of admission is associated with decreased mortality rates. Negative FNA
      findings, nondiagnostic radiographs, and admission to a nonsurgical service
      correlate with delay in definitive operative intervention.

PMID- 8542095
TI  - Postexcisional recurrence of carcinoma of the breast.

PMID- 8542096
TI  - Epidemiology, diagnosis, precautions, and policies of intraoperative anaphylaxis
      to latex.

PMID- 8542097
TI  - Epidemiology, diagnosis, precautions, and policies of intraoperative anaphylaxis
      to latex.

PMID- 8542098
TI  - The methodologic quality of randomization as assessed from reports of trials in
      specialist and general medical journals.
AB  - OBJECTIVE: To assess the quality of randomization from reports of trials in a
      sample of specialist journals, and to compare those results with a similar
      assessment from a sample of general medical journals. DESIGN: Evaluation of all
      206 reports of parallel-group randomized trials published in the 1990 and 1991
      volumes of four journals of obstetrics and gynecology and of 81 reports of trials
      published during 1987 in four general medical journals. RESULTS: Of the reports
      published in the specialist and in the general medical journals, only 32% and
      48%, respectively, reported having used an adequate method to generate random
      numbers; only 23% and 26%, respectively, contained information showing that steps
      had been taken to conceal assignment until the point of treatment allocation; and
      merely 9% and 15%, respectively, described adequate methods of both sequence
      generation and allocation concealment. In those reports of trials that had
      apparently used unrestricted randomization, the differences in sample sizes
      between treatment and control groups were much smaller than would be expected by
      chance, and that feature was more marked in the specialist journals. In reports
      of trials in which hypothesis tests had been used to compare baseline
      characteristics, only 2% of tests reported in specialist journals and 4% of tests
      reported in general journals were statistically significant, lower than the
      expected rate of 5%. CONCLUSIONS: Generating unbiased comparison groups requires
      proper randomization, yet the reports in these specialist and general journals
      usually provided inadequate or unacceptable information. Additional analyses
      suggest that nonrandom manipulation of comparison groups and selective reporting
      of baseline comparisons may have occurred.

PMID- 8542099
TI  - Effect of intensive insulin therapy on abnormal circadian blood pressure pattern
      in patients with type I diabetes mellitus.
AB  - OBJECTIVE: To assess the effect of tight glycemic control on the abnormal
      circadian BP pattern associated with IDDM. DESIGN: Retrospective, randomized
      control trial. SETTING: Diabetes Research Institute, ambulatory. PATIENTS:
      Seventy-four IDDM patients (22M/52F) on intensive subcutaneous insulin therapy
      (ISIT) were selected for this study. INTERVENTIONS: Group A patients (11M/25F)
      underwent, in addition to ISIT, weekly chronic intermittent intravenous insulin
      therapy (CIIIT) (TT Aoki et al, Lancet, 1993, 432:515-8). Group B patients
      (11M/27F) were continued on ISIT alone. All study patients were followed for 3
      months on this regimen. They were seen weekly by the investigators and underwent
      monthly HbA1c determinations and 24-h ambulatory BP monitoring. RESULTS: Glycemic
      control improved significantly in group A subjects (HbA1c decreased from 7.9% to
      7.2%, p = 0.0002) but changed little in the group B subjects (p = NS). The
      night/day systolic BP ratio decreased from 0.97 to 0.94 (-3.10%) in group A and
      increased from 0.95 to 0.98 (+3.16%) in group B subjects (p = 0.224). The
      night/day diastolic ratio decreased from 0.93 to 0.90 (-3.23%) in group A and
      increased from 0.91 to 0.94 (+3.29%) in group B subjects (p = 0.0037).
      CONCLUSIONS: CIIIT performed in IDDM patients on ISIT further improves their
      glycemic control and tends to reverse or at least prevent further deterioration
      of their abnormal circadian BP pattern.

PMID- 8542100
TI  - Oxygen therapy for pediatric obstructive sleep apnea syndrome: how safe? How
      effective?

PMID- 8542101
TI  - Pretreatment with allergen prevents immediate hypersensitivity and airway
      hyperresponsiveness.
AB  - The ability of subcutaneous pretreatment with an immunogenic peptide derived from
      Fel d I, the major cat protein, to suppress the development of allergic responses
      was examined in a mouse model of antigen-induced sensitization. BALB/c mice
      exposed to aerosolized Fel d I chain 1 peptide developed antigen-specific IgE
      responses, immediate cutaneous reactivity to the peptide, and increased airway
      responsiveness (AR). Both subcutaneous and intraperitoneal administration of the
      peptide prior to sensitization caused a 50% reduction in cutaneous reactivity
      which was associated with a decrease in serum anti-Fel d I chain 1 IgE and IgG1
      antibody responses and an increase in specific IgG. Pretreatment with the peptide
      also suppressed spleen and lymph node proliferative responses to the peptide.
      However, only subcutaneous peptide injections could prevent the development of
      increased AR. Transfer of spleen cells from subcutaneously peptide-treated mice
      to sensitized recipients reduced serum antigen-specific IgE and IgG1 antibody
      responses and skin test reactivity, and prevented alterations in AR. These data
      suggest that IgE (and IgG1) responses and airway hyperresponsiveness induced by
      allergen sensitization via the airways can be modulated by subcutaneous
      administration of peptide. Further, the results define a model for investigating
      the modulatory effects of subcutaneous administration of immunogenic peptides or
      protein on an ongoing allergic response.

PMID- 8542102
TI  - Computed tomography of the lungs in asthma: influence of disease severity and
      etiology.
AB  - Airways remodelling is a feature of longstanding asthma, but may differ in
      persons with allergic and nonallergic asthma. To assess airways remodelling
      indirectly, we compared permanent CT-scan abnormalities in 70 subjects with
      allergic (median age: 30 yr) and 56 with nonallergic asthma (median age: 54.5 yr)
      who had had asthma of similar duration. None of the subjects were smokers. Asthma
      severity was assessed by Aas score and FEV1. Permanent high-resolution computed
      tomographic (HR-CT) scan abnormalities were characterized. In comparison with
      allergic asthmatic subjects, those with nonallergic asthma had a significantly
      greater frequency of cylindric (p < 0.0007, Mann-Whitney U test) and varicose (p
      < 0.004) bronchiectasis, emphysema (p < 0.0003), bronchial recruitment (p <
      0.0001), and sequellar linear shadows (p < 0.0001). There was a significant
      correlation between Aas score and emphysema (p < 0.0001 for nonallergic and p <
      0.0005 for allergic asthma; Kendall's test method) or Aas score and sequellar
      linear shadows (p < 0.007, nonallergic asthma). There was a significant increase
      in the extent of permanent abnormalities with increasing severity and duration of
      asthma in both groups. Patients with brittle asthma had few permanent
      abnormalities. This study confirms that after a similar course of the disease,
      patients with nonallergic asthma have a more extensive remodelling of the airways
      than those with allergic asthma.

PMID- 8542103
TI  - Maximal bronchoconstriction in humans. Relationship to deep inhalation and airway
      sensitivity.
AB  - We hypothesized that maximal bronchoconstriction can be predicted from the
      bronchomoter effect of deep inhalation (DI) and the degree of airway sensitivity
      to methacholine (MCh). We studied 26 healthy or mildly asthmatic subjects with
      limited response to MCh (maximal FEV1 decrease, 23 +/- 9 SD%; Group 1) and 26
      subjects with moderate to severe asthma with exaggerated response (maximal FEV1
      decrease > 40%, Group 2). The effect of DI was quantified as the linear
      regression coefficient of the percent decrements of maximal (Vm50) versus partial
      (Vp50) forced expiratory flow at 50% of FVC over the initial steps of challenge
      (MP slope). Airway sensitivity was inferred from the MCh doses (PDs) causing Vm50
      or Vp50 to decrease by 40% or FEV1 by 15%. The absence of limit to
      bronchonstriction was predicted by either MP slope or any PD with accuracies
      between 71 and 81%, but with an accuracy of 87% by a discriminant function
      including MP slope and PD40Vp50. Within Group 1, the maximal FEV1 decrease
      correlated linearly with MP slope (r2 = 0.41); but it was better predicted by a
      multiple regression including MP slope and PD40Vp50 (In mg) (r2 = 0.54). We
      conclude that the magnitude of the bronchodilator effect of DI during induced
      bronchoconstriction and airway sensitivity predict the level of maximal
      bronchoconstriction in vivo. We speculate that these parameters reflect some of
      the mechanisms modulating the response to bronchoconstrictor stimuli such as
      airway wall structure, airway-to-parenchymal interdependence, and contractile
      properties of airway smooth muscle.

PMID- 8542104
TI  - Corticosteroid-sparing effect of azelastine in the management of bronchial
      asthma.
AB  - The objective of this double-blind trial was to evaluate the corticosteroid
      sparing effect of azelastine in patients with chronic bronchial asthma. A total
      of 193 subjects received either 6 mg of azelastine twice per day or placebo (in a
      2:1 ratio) in combination with beclomethasone dipropionate (6 to 16 inhalations
      per day). The number of daily inhalations of the corticosteroid was reduced until
      maximum reduction or elimination was achieved. Patients then entered a 12-wk
      maintenance period, during which patients were maintained on their lowest
      possible dose of inhaled corticosteroid. Compared with placebo, the azelastine
      group had a statistically significantly greater overall median reduction in
      inhaled corticosteroids (4.9 puffs/day for azelastine versus 3.1 puffs/day for
      placebo; p < or = 0.010) during the maintenance period. The azelastine group also
      had a statistically significantly higher percentage of patients with reductions
      of > or = 50% and > or = 75% from the baseline level (53 and 31%, respectively,
      for azelastine versus 34 and 14%, respectively, for placebo; p < or = 0.028). The
      results demonstrated that azelastine, 6 mg twice per day, can reduce the need for
      inhaled corticosteroids in patients with chronic bronchial asthma and not lead to
      a deterioration in pulmonary function.

PMID- 8542105
TI  - Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine
      induced bronchospasm.
AB  - Nitric oxide (NO) reduces airway tone in the methacholine-treated guinea pig. We
      examined whether low levels of inhaled NO gas would relax airway smooth muscle
      tone in patients with mild asthma subjected to methacholine-induced bronchospasm.
      Thirteen adult volunteers with mild asthma inspired increasing concentrations of
      methacholine until their baseline forced expiratory volume in one second (FEV1,
      3.29 +/- 0.17 L, mean +/- SEM) decreased by > or = 20% (2.33 +/- 0.18 L, p <
      0.01). Thereafter, they sequentially inhaled 100 parts per million (ppm) NO, 40%
      O2; 40% O2; and 100 ppm NO, 40% O2 while spirometry was performed. Subsequent
      inhalation of isoproterenol returned the FEV1 levels to baseline. Inhaling 100
      ppm NO increased FEV1 to 2.66 +/- 0.18 L (p < 0.01), and this increase was
      maintained after NO was discontinued. FEV1 did not change during the second
      period of NO inhalation. Similar results were observed for vital capacity, but no
      significant effect was noted on forced expiratory flow at 25% of vital capacity
      or peak expiratory flow. Subjects were then divided into a responder subgroup,
      which showed a mean increase in FEV1 after initial NO inhalation of 560 +/- 150
      ml, and a nonresponder subgroup, which showed a mean increase in FEV1 of 129 +/-
      29 ml. Our data suggest that inhalation of nitric oxide by patients with mild
      asthma with methacholine-induced bronchospasm results in a minor but significant
      relaxation of airway tone.

PMID- 8542106
TI  - Ragweed antigen causes interleukin-8 production in sensitized dog trachea.
AB  - Antigen challenge in allergic subjects and in sensitized animals causes
      recruitment of neutrophils as well as eosinophils into the airways. In this
      study, we asked whether interleukin-8 (IL-8) is involved in the recruitment of
      neutrophils into the airways after antigen challenge. We administered ragweed
      antigen to an isolated, superfused tracheal segment of ragweed-sensitized dogs.
      Local tracheal instillation of the antigen caused an increase in IL-8
      concentration and increases in both the number of recruited neutrophils and
      myeloperoxidase activity (one indicator of neutrophil activation in the recruited
      cells). The increase in IL-8 concentration was observed earlier than both the
      neutrophil recruitment and the increase in myeloperoxidase activity in the
      tracheal superfusate. Superfusate removed from the trachea 8 h after antigen
      challenge showed marked neutrophil chemotactic activity in a microchemotaxis
      chamber, and this activity was inhibited (mean, 75.6%) by a blocking antibody to
      dog IL-8. We conclude that ragweed antigen causes neutrophil recruitment into the
      airways at least in part because of IL-8 production.

PMID- 8542107
TI  - House dust mite allergens. A major risk factor for childhood asthma in Australia.
AB  - If house dust mite allergen (Der p I) is an important cause of asthma, there
      should be a direct relationship between level of exposure to this allergen and
      asthma severity. To examine this, we studied six large random samples of children
      in different regions of New South Wales, Australia. We measured recent wheeze by
      questionnaire, airway hyperresponsiveness (AHR) by histamine inhalation test and
      sensitization to house dust mites by skin prick tests. Current asthma was defined
      as the presence of recent wheeze and AHR. We measured Der p I levels in the beds
      of approximately 80 children in each region. In regions where Der p I levels were
      high, more children were sensitized to house dust mites, and these children had
      significantly more AHR and recent wheeze. After adjusting for sensitization to
      other allergens, we found that the risk of house dust mite-sensitized children
      having current asthma doubled with every doubling of Der p I level. There was a
      modest correlation between AHR and Der p I exposure in individuals (r = 0.23, p <
      0.03). These data suggest that house dust mite allergens are an important cause
      of childhood asthma and that reducing exposure to these allergens could have a
      large public health benefit in terms of asthma prevention.

PMID- 8542108
TI  - Time course of interleukin-6 and tumor necrosis factor-alpha increase in serum
      following inhalation of swine dust.
AB  - Inhalation of swine dust induces airway inflammation and general symptoms, such
      as fever and malaise. In the present investigation, the presence and time course
      of changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in
      serum were studied to evaluate possible mechanisms by which inhalation of swine
      dust induces general symptoms. A group of 14 previously nonexposed subjects
      weighed swine for 3 h. The average +/- SD inhalable dust concentration was 22.4
      +/- 4.7 mg/m3 and endotoxin, 1.2 +/- 0.4 microgram/m3. TNF-alpha in serum
      increased from 2.5 (1.8 to 3.1) ng/L (median, interquartile range) before
      exposure to maximum values 10.0 (4.6 to 15.7) ng/L between 3 and 5 h after the
      start of exposure. IL-6 increased from less than 1.5 to 21.4 (18.6 to 33.6) ng/L
      4 to 11 h after the start of exposure. Maximum IL-6 occurred 1 to 5 h after the
      maximum TNF-alpha. In many subjects, however, an early rise in IL-6 parallel to
      the change in TNF-alpha was seen. The results that some of the peripheral
      reactions to swine dust might be mediated by TNF-alpha and IL-6. The early rise
      in IL-6 implies multiple origins of the IL-6.

PMID- 8542109
TI  - Mechanical ventilation increases substance P concentration in the vagus,
      sympathetic, and phrenic nerves.
AB  - Substance P (SP), a neurotransmitter localized to primary sensory neurons, is
      found in the vagus nerve, nodose ganglion, sympathetic chain, and phrenic nerve
      in various animal species. However, the changes in endogeneous SP concentration
      under various circumstances that involve the participation of cardiorespiratory
      afferent nerves are still unexplored. In the present study, attention was focused
      on the variations in SP content measured by radioimmunoassay (RIA) in respiratory
      afferent nerves (vagus nerve, cervical sympathetic chain, phrenic nerve) and
      respiratory muscles (diaphragm, intercostal muscles) during positive inspiratory
      pressure (PIP) breathing alone or PIP with an expiratory threshold load (ETL) in
      rabbits. SP was found in all sampled structures in spontaneously breathing
      control animals, prevailing in the nodose ganglion. Left-versus right-sided
      differences were noticed in nerves. As compared with that in control animals, the
      SP concentration was markedly higher in vagal and sympathetic nervous structures
      during PIP or PIP with ETL, and also in the phrenic nerve during ETL breathing.
      The SP content did not vary in respiratory muscles. These observations suggest
      that two very common circumstances of mechanical ventilation are associated with
      an increased SP concentration in nervous structures participating in the control
      of breathing.

PMID- 8542110
TI  - Risk factors for nosocomial pneumonia: comparing adult critical-care populations.
AB  - The purpose of the study was to examine risk factors for nosocomial pneumonia in
      the surgical and medical/respiratory intensive care unit (ICU) populations. In a
      public teaching hospital, all cases of nosocomial pneumonia in the surgical and
      medical/respiratory ICUs (n = 20, respectively) were identified by prospective
      surveillance during a 5-yr period from 1987-1991. Each group of ICU cases was
      compared with 40 ICU control patients who did not acquire pneumonia, and analyzed
      for 25 potential risk factors. Surgical ICU patients were found to have
      consistently higher rates of nosocomial pneumonia than medical ICU patients (RR =
      2.2). The strongest predictor for nosocomial pneumonia in both the surgical and
      medical/respiratory ICU groups was found to be prolonged mechanical ventilation
      (> 1 d) resulting in a 12-fold increase in risk over nonventilated patients.
      APACHE III score was found to be predictive of nosocomial pneumonia in the
      surgical ICU population, but not in the medical/respiratory ICU population. We
      conclude that certain groups deserve special attention for infection control
      intervention. Surgical ICU patients with high APACHE scores and receiving
      prolonged mechanical ventilation may be at the greatest risk of acquiring
      nosocomial pneumonia of all hospitalized patients.

PMID- 8542111
TI  - Time course of procoagulant activity and D dimer in bronchoalveolar fluid of
      patients at risk for or with acute respiratory distress syndrome.
AB  - Intraalveolar fibrin deposition is a typical finding in acute lung injury and is
      not necessarily harmful. However, persistence of intraalveolar fibrin deposit may
      lead to hyaline membrane formation and subsequent alveolar fibrosis, a histologic
      hallmark of late stages of acute respiratory distress syndrome (ARDS). Thus,
      timing of the intraalveolar clotting disorder seems to be critical. To explore
      the time course of factors contributing to fibrin deposition and resolution, we
      sequentially analyzed procoagulant activity and fibrin degradation (by D dimer)
      in bronchoalveolar lavage (BAL) fluid of patients developing ARDS and those at
      risk for, but finally not developing, the syndrome. A total of 36 bronchoalveolar
      lavages were performed in 11 patients developing ARDS and 15 lavages in 10
      patients at risk for but not developing this syndrome. All patients were admitted
      to the intensive care unit for the treatment of sepsis, trauma, or shock. In
      early phases of ARDS, the procoagulant activity (PCA) in BAL was significantly
      higher than in the patients at risk, 320 +/- 83 U (mean +/- SEM) versus 50 +/- 25
      U, p < 0.05. A similar difference was noted in subacute stages (280 +/- 91 versus
      46 +/- 16 U, p < 0.05). In early ARDS we observed higher levels of D dimer in BAL
      than in patients at risk: 1,841 +/- 827 versus 293 +/- 134 ng/ml, p < 0.05.
      Similarly, values of D dimer in the subacute phase were 2,776 +/- 836 versus 237
      +/- 125 ng/ml, p < 0.05. In ARDS as well as in the at-risk group, D dimer in BAL
      fluid showed good correlation with the polymorphonuclear leukocyte count and with
      protein content of BAL. There was no correlation between plasma and BAL levels of
      D dimer. We conclude that in ARDS both the procoagulant pathway and the fibrin
      degradation are markedly activated compared with these in patients at risk but
      finally not developing this syndrome. These findings expand our understanding of
      intraalveolar coagulation abnormalities by providing evidence of increased fibrin
      breakdown in this syndrome.

PMID- 8542112
TI  - Effects of breathing route, temperature and volume of inspired gas, and airway
      anesthesia on the response of respiratory output to varying inspiratory flow.
AB  - The determinants of the response of the respiratory output to inspiratory flow
      rates (VI) were examined in awake normal subjects. Subjects were connected to a
      volume-cycle ventilator in the assist/control mode, and VI was increased in steps
      from 30 to 90 L/min and then back to 30 L/min. VI pattern was square, and all
      breaths were subject-triggered. In six subjects the effects of breathing route
      (nasal or mouth) and temperature and volume of inspired gas (Protocol A) and in 8
      subjects the effects of airway anesthesia (upper and lower airways; Protocol B)
      on the response of respiratory output to varying VI were studied. In Protocol B,
      in order to calculate muscle pressure during inspiration (Pmus), respiratory
      system mechanics were measured using the interrupter method at end-inspiration.
      Independent of conditions studied, breathing frequency increased significantly
      and end-tidal concentration of CO2 decreased as VI increased. The response was
      graded and reversible and not affected by breathing route, temperature and volume
      of inspired gas, and airway anesthesia. With and without airway anesthesia
      (Protocol B), neural inspiratory and expiratory time and neural duty cycle,
      estimated from Pmus waveform, decreased significantly as VI increased. At all
      conditions studied, the rate of change in airway pressure prior to triggering the
      ventilator tended to increase as VI increased. The changes in timing and drive
      were nearly complete within the first two breaths after transition, with no
      evidence of adaptation during a given VI period. We conclude that VI exerts an
      excitatory effect on respiratory output which is independent of breathing route,
      temperature and volume of inspirate, and airway anesthesia. The response most
      likely is neural in origin, mediated through receptors not accessible to
      anesthesia, such as those located in the chest wall or below the airway mucosa.

PMID- 8542113
TI  - Surfactant alterations in severe pneumonia, acute respiratory distress syndrome,
      and cardiogenic lung edema.
AB  - Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities
      in 153 patients with acute respiratory failure necessitating mechanical
      ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the
      absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and
      PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was
      subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16),
      interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with
      healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL
      classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified
      in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was
      used to assess the percentage of large surfactant aggregates (LSA) and the
      biophysical properties of the surfactant (pulsating bubble surfactometer). All
      groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in
      the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in
      alveolar protein load. Marked changes in the PL profile were noted throughout the
      groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and
      an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations
      of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values
      approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of
      supernatant protein and from 20 to 35 mN/m in recombination with leaked protein
      in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed
      those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with
      extensive metabolic changes. All surfactant changes were absent in CLE except for
      a slight inhibition of surface activity by proteins. We conclude that pronounced
      surfactant abnormalities, comparable to those in ARDS in the absence of lung
      infection, occur in different entities of severe PNEU, but not in CLE.

PMID- 8542114
TI  - Resource use implications of do not resuscitate orders for intensive care unit
      patients.
AB  - This study describes the use of do not resuscitate (DNR) orders for ICU patients
      in four northeastern U.S. teaching hospitals and investigates the relationship
      between DNR orders and length of stay. The use of detailed data from the
      mortality probability model (MPM II) study on 6,290 consecutive ICU admissions to
      general adult medical and surgical ICUs during 1989 through 1991 allows us to
      control for severity of illness and the time during the ICU stay at which the DNR
      order was entered. About 12.8% of patients were DNR during their ICU stay,
      including more than half of nonsurvivors. The percentage of patients with DNR was
      higher for older and more severely ill patients. Most DNR orders were issued
      after 72 h in the ICU, but many were issued during the first ICU day.
      Nonsurvivors with early (first 24 h) DNR had shorter mean and median ICU and
      hospital stays than the comparison group of non-DNR patients. The percentage of
      patients with very long ICU (> 30 d) and hospital (> 60 d) stays was smaller
      among DNR patients. The use of DNR orders, particularly early in the ICU stay,
      may be associated with significant resource use reduction for an identifiable
      group of patients.

PMID- 8542115
TI  - Skeletal muscle microvascular blood flow and oxygen transport in patients with
      severe sepsis.
AB  - To compare skeletal muscle microvascular blood flow at rest and during reactive
      hyperemia in septic patients, a prospective, controlled trial was conducted on 16
      patients with severe sepsis and a control group of 10 patients free of infection
      in the intensive care unit of a university hospital. Systemic hemodynamics, whole
      body oxygen transport, and skeletal muscle microvascular blood flow at rest and
      during reactive hyperemia were measured. Reactive hyperemia was produced by
      arrest of leg blood flow with a pneumatic cuff; on completion of the 3 min
      ischemic phase the occluding cuff was rapidly deflated to 0. Hemodynamic and
      oxygen-derived variables were determined invasively. Skeletal muscle
      microvascular blood flow data were obtained using a laser Doppler flowmetry
      technique and values expressed in millivolts. Whole-body oxygen delivery in
      septic patients was increased compared with control subjects. Resting skeletal
      muscle blood flow was decreased in septic patients compared with control subjects
      (233 +/- 52 versus 394 +/- 93 mV; p < 0.05). Peak flow during reactive hyperemia
      was also decreased in septic patients compared with control subjects (380 +/- 13
      versus 2,033 +/- 853 mV; p < 0.05). Cyclic variation in blood flow (vasomotion)
      was observed in control subjects but not in septic patients. Skeletal muscle
      microvascular perfusion is altered in patients with severe sepsis despite normal
      or elevated whole-body oxygen delivery. These microvascular abnormalities may
      further compromise tissue nutrient flow and may contribute to the development of
      organ failure in septic patients.

PMID- 8542116
TI  - Vascular injury in isolated sheep lungs. Role of ischemia, extracorporeal
      perfusion, and oxygen.
AB  - Extracorporeal perfusion of isolated sheep lungs with blood after 30 min of
      ischemia caused injury manifested by polymorphonuclear (PMN) leukocyte
      sequestration, pulmonary hypertension, thromboxane release, and increased
      pulmonary vascular permeability. To determine the roles of ischemia,
      extracorporeal perfusion, and oxygen in this injury, lungs ventilated with 28% O2
      5% CO2 and subjected to 30 min of ischemia followed by 180 min of perfusion
      (ischemic-perfused, n = 23) were compared with lungs subjected to (1) ischemia
      without perfusion (ischemic, n = 7), (2) perfusion without ischemia (perfused, n
      = 20), or (3) both ischemia and perfusion during ventilation with 95% N2 (anoxic
      ischemic-perfused, n = 15). Compared with ischemic-perfused lungs, ischemic lungs
      had an increased reflection coefficient for albumin (sigma alb, 0.82 +/- 0.03
      versus 0.54 +/- 0.05) and decreased filtration coefficient (Kf, 0.05 +/- 0.01
      versus 0.11 +/- 0.03 g.min-1.mm Hg-1.100 g-1). Perfused lungs had increased
      pulmonary hypertension, lung PMN leukocytes, and sigma alb (0.74 +/- 0.05); Kf
      was not different. Anoxic ischemic-perfused lungs had decreased pulmonary
      hypertension and thromboxane release, but sigma alb and Kf were not altered.
      These results suggest that extracorporeal perfusion caused PMN leukocyte
      sequestration, thromboxane release, and pulmonary hypertension, whereas ischemia
      caused derecruitment of vascular surface area. Injury required both ischemia and
      perfusion, but it was not decreased by anoxia, suggesting that oxygen radicals
      were not involved.

PMID- 8542117
TI  - Increases in peripheral oxygen demand affect blood flow distribution in
      hemorrhaged dogs.
AB  - Blood flow redistribution away from the gastrointestinal tract and kidney occurs
      during progressive hemorrhage and stress. However, the effects of remote
      increases in oxygen demand on a circulation with limited ability to respond have
      not been described. Thus, we observed the effect of remote increases in oxygen
      demand on splanchnic and renal blood flow in hemorrhaged dogs. Nine alpha
      chloralose-anesthetized, splenectomized dogs were subjected to hemorrhage of 10
      ml/kg followed by an additional 5 ml/kg. At each of these two stages, bilateral
      femoral nerve stimulation was used to increase lower extremity oxygen demand
      while lower extremity, splanchnic, renal blood flows and arteriovenous oxygen
      content differences were monitored. Hemorrhage was associated with redistribution
      of blood flow away from the lower extremities and kidneys and increasing the
      oxygen extraction ratio of the splanchnic bed. Lower extremity stimulation
      increased whole-body oxygen consumption (7.3 +/- 2.7 to 11.4 +/- 4.5 ml
      O2/min/kg, p < 0.01). If arterial pressure remained stable during stimulation (>
      90% of baseline value, n = 9), visceral organ blood flow did not change. However,
      when blood pressure decreased (< 70% of baseline, n = 8), splanchnic (226.3 +/-
      143.5 to 140.9 +/- 126.4 ml/min, p < 0.01) and renal (59.6 +/- 30.2 to 28.5 +/-
      26.0 ml/min, p < 0.01) blood flow also decreased. Thus, in the anesthetized,
      hemorrhaged dog, increased peripheral oxygen demand results in further
      redistribution of blood flow away from the gastrointestinal tract and kidneys
      only when there is a concurrent decrease in blood pressure.

PMID- 8542118
TI  - Modulation of hypoxic pulmonary vasoconstriction by antioxidant enzymes in red
      blood cells.
AB  - To determine whether antioxidant mechanisms within red blood cells (RBCs)
      significantly contribute to preserving hypoxic pulmonary vasoconstriction (HPV)
      in both the absence and the presence of oxidative stress, we investigated HPV
      changes in isolated rabbit lungs perfused with solutions containing RBCs treated
      with various inhibitors of superoxide dismutase (SOD), anion channels, catalase
      (CAT), or glutathione peroxidase (GSH-Px). Perfusion was maintained at a constant
      flow rate of 70 ml/min, and lung temperature at 37 to 38 degrees C. Hematocrit
      was adjusted to 7%. In the absence of overt oxidative stress, HPV was
      significantly enhanced in the perfusate containing control RBCs (untreated RBCs)
      as compared with that in Krebs-Henseleit buffer. Inhibition of SOD, CAT, and GSH
      Px within RBCs, as well as anion channels located on the RBC membrane, had little
      influence on HPV. Neither exogenous SOD nor CAT altered HPV. In the presence of
      high levels of reactive oxygen species (ROS), generated by addition of xanthine
      (100 microM) and xanthine oxidase (10 mU/ml) to the reservoir, HPV was
      considerably suppressed in the perfusate containing only buffer but was restored
      in the perfusate with control RBCs. Inhibition of CAT or GSH-Px in RBCs preserved
      the HPV, whereas inhibition of SOD or anion channels failed to preserve HPV
      obtained during exposure to high ROS levels. Addition of exogenous SOD, but not
      CAT, to the perfusate containing RBCs in which endogenous SOD had been inhibited
      restored HPV under high ROS conditions. In conclusion, (1) although RBCs augment
      HPV in the absence of ROS, this finding is not attributable to the antioxidants
      in RBCs. (2) RBCs restore HPV upon exposure to high ROS. This finding may well be
      explained by antioxidant mechanisms operating within RBCs, especially those of
      endogenous SOD.

PMID- 8542119
TI  - Environmental tobacco smoke, wheezing, and asthma in children in 24 communities.
AB  - The association of exposure to environmental tobacco smoke (ETS) at home with
      asthma and several measures of wheeze was examined among 11,534 children aged 8
      to 11 yr in 24 communities in the United States and Canada in 1988 through 1990.
      Information on the child's respiratory symptoms in the past year and history of
      exposure to ETS was provided by the child's mother on a questionnaire. After
      adjusting for potential confounders, children currently exposed to ETS were at
      greater risk of wheezing with colds (odds ratio [OR] = 1.7; 95% confidence
      interval [95% CI], 1.4 to 1.9), going to a hospital emergency room for wheeze (OR
      = 1.6; 95% CI, 1.2 to 2.2), and having persistent wheeze (OR = 1.4; 95% CI, 1.1
      to 1.8). The relative odds of these symptoms increased with exposure level, and
      there was no evidence of a difference in the association with smoking by mother,
      father, or other adults. In contrast to wheeze symptoms, active doctor-diagnosed
      asthma and asthma medication use were not significantly associated with ETS
      exposure at home, possibly reflecting underdiagnosis of asthma, reporting bias,
      or smoking cessation by parents whose child is labeled asthmatic. We conclude
      that exposure to ETS is associated with wheezing symptoms, medical therapy for
      wheezing, and wheezing-related emergency department visits in U.S. and Canadian
      children.

PMID- 8542120
TI  - Decrements in spirometry values associated with chlorine gassing events and pulp
      mill work.
AB  - In a previous study of older pulp and paper workers in Berlin, New Hampshire,
      decrements in spirometry results associated with accidental exposures to high
      levels of irritant gases depended on cumulative levels of pulp mill exposure and
      cigarette smoking. Many of those subjects were older and retired. A new study was
      initiated to assess whether gassing events were a problem among current workers.
      Three hundred white male pulp and paper workers from the mill in Berlin, New
      Hampshire, were surveyed in 1992. Testing included spirometry and questionnaires.
      The mean age was 40.4 yr, and the mean tenure with the company was 18.5 yr. A
      total of 105 of the 300 subjects (35%) reported ever having an episode of high
      exposure to chlorine gases (i.e., being gassed). The percentage gassed was 51%
      for pulp mill workers and only 13% for other employees. For subjects with no more
      than 26 pack-years of cigarette smoking, obstruction (i.e., abnormally low FEV1
      and FEV1/FVC) was observed only among those with a history of gassing. Also, the
      combination of high cigarette smoking (i.e., > 26 pack-years) and gassing had a
      greater than additive effect on obstruction. These findings suggest that
      additional controls are needed to minimize the number of gassing events in this
      and other chemical pulp mills.

PMID- 8542121
TI  - Effect on cortical and trabecular bone mass of different anti-inflammatory
      treatments in preadolescent children with chronic asthma.
AB  - Bone metabolism and density have been shown to be abnormal in adult asthmatic
      patients treated with inhaled corticosteroids. Because the largest increases in
      bone growth and mineral deposition occur during childhood and adolescence, we
      performed a cross-sectional evaluation of cortical and trabecular bone mass by
      dual-photon absorptiometry at the proximal one third of the radius (cortical
      bone) and by dual-energy X-ray absorptiometry at the L2-L4 lumbar spine
      (trabecular bone) in 64 prepubertal asthmatic children receiving beclomethasone
      dipropionate (BDP) or cromolyn sodium (CS). Dual-energy X-ray absorptiometry was
      performed by anteroposterior scan and also by lateral vertebral scan in order to
      exclude the posterior elements of the vertebrae, which are composed mainly of
      cortical bone and which are less sensitive to the negative effect of steroids.
      Furthermore, we calculated "volumetric" bone density, dividing lateral mineral
      content by the vertebral volume. Bone mineral areal density and volume bone
      density did not differ in children receiving BDP for 6.7 +/- 1.3 mo at a mean
      dose of 319.3 +/- 130 micrograms/d compared with those in children treated with
      CS. Furthermore, anteroposterior bone density in our study population was in
      agreement with published normative data and with that of normal age-related
      healthy nonasthmatic children living in the same area and with the same dietary
      intake of calcium. No normal values are available for lateral and calculated
      volume bone density. In conclusion, treatment with BDP does not appear to have an
      adverse effect on bone mass in prepubertal children with mild moderate asthma.
      Longitudinal studies should be performed in order to evaluate the effect of early
      introduction of inhaled corticosteroids in children with mild asthma.

PMID- 8542122
TI  - Exogenous stimuli and circadian peak expiratory flow variation in allergic
      asthmatic children.
AB  - The influence of exogenous factors in the home on the circadian variation of
      airway obstruction has not been fully assessed in children with asthma. The aim
      of the present study was to investigate the contribution of exogenous stimuli to
      the degree of peak expiratory flow (PEF) variability during 24 h. Fifty-five
      children (33 boys and 22 girls; mean age, 9.3 +/- 1.7 yr) with symptoms of
      asthma, increased bronchial responsiveness, and a solitary allergy to house dust
      mite (HDM) participated. Their asthma symptoms were well-controlled for at least
      4 mo with daily inhaled corticosteroids (ICS) and beta 2-adrenergic drugs if
      needed. Symptoms, peripheral blood eosinophils, total IgE, and specific IgE to
      HDM were assessed. Spirometry and PC20 histamine were performed. PEF amplitudes
      during 24 h (highest minus lowest as a percentage of the day's mean value) were
      obtained at home during and 6 d after withdrawal of ICS. Dust samples were
      collected from the total area of the living rooms, bedrooms, mattresses (n = 25),
      and classrooms to obtain the HDM allergen (HDMA) exposure to Der p I and Der p
      II. Family smoking habits, presence of pets, and types of floor-covering were
      recorded on a checklist. Mean PEF amplitude did not increase after withdrawal of
      ICS, but absolute PEF values were significantly lower (p = 0.05) at midnight and
      4:00 A.M. Twenty-six children (47%) were exposed to environmental tobacco smoke
      (ETS), and 23 (42%) kept pets. Mattresses contained significantly higher amounts
      of HDMA compared with other locations. PEF amplitude after withdrawal of ICS was
      significantly higher in children exposed to ETS, a pet, or a high HDMA level in
      their mattress than in children who were not exposed (ETS: 29.7% [3.9 to 56.6]
      versus 19.4% [0.0 to 56.6], p < 0.05; pets: 31.4% [9.7 to 52.5] versus 21.9% [0.0
      to 56.6], p < 0.05; high HDMA level in the mattress: 35.5% [10.2 to 56.6] versus
      21.4% [3.9 to 56.6], p < 0.05). These factors combined with age and PC20
      histamine and its interaction with ETS, especially in mild to moderate asthma,
      explained 48.4% of the variance of the PEF amplitude after withdrawal of ICS.
      Exogenous stimuli such as exposure to ETS, pets, and high HDMA levels in
      mattresses contribute to an increased circadian PEF amplitude after withdrawal of
      ICS and therefore to nocturnal worsening of asthma in HDM-allergic asthmatic
      children. Moreover, ETS exposure seems to especially worsen PEF variability in
      children with mild to moderately severe bronchial responsiveness.

PMID- 8542123
TI  - Lung cancer chemotherapy. Response-survival relationship depends on the method of
      chest tumor response evaluation.
AB  - In a previous study we found that tumor responses as assessed by CT scan and
      fiberoptic bronchoscopy are sometimes discordant. We hypothesize that the
      response-survival relationship might vary according to the method of tumor
      response assessment. In a multivariate analysis of survival using the landmark
      method, we evaluated the prognostic significance of tumor response assessed by CT
      scan or fiberoptic bronchoscopy together with bronchial tumor location and
      histology of bronchial biopsies at restaging. A total of 133 lung cancer patients
      (50 small cell lung cancers and 83 non-small cell lung cancers) were entered in
      controlled chemotherapy trials and prospectively evaluated for chest tumor
      response by CT scan and fiberoptic bronchoscopy (FOB). Only 106 patients were
      fully evaluable for response by both methods. For these patients, a statistical
      concordance was observed between the two tests (kappa = 0.271; p < 0.001). There
      was a significant correlation between response and survival whatever the test
      used. However, only CT scan evaluation resulted in a classification showing that
      the more unfavorable the response stage was, the worse the survival became with
      no intersection between survival curves. Cox's hazard model demonstrated that CT
      evaluated progression, proximal bronchial location at second FOB (intermediate,
      main bronchus or trachea) and positive histologic status at restaging were all
      prognostic determinants of poor survival. In conclusion, CT-evaluated response
      led to the best response-survival relationship as this method classified patients
      into four groups with different outcomes. Fiberoptic bronchoscopy should be
      avoided in patients who were found to have no endobronchial lesion during the
      pretreatment staging. For patients with pretreatment assessable endobronchial
      lesions, the decision of a second FOB depends on the results of CT restaging: FOB
      is probably unnecessary in patients for whom progression is disclosed by CT scan.
      In patients for whom CT scan discloses tumor response or stabilization, bronchial
      tumor location and histology of bronchial biopsies at second FOB are independent
      prognostic factors.

PMID- 8542124
TI  - Effects of changes in central venous pressure on upper airway size in patients
      with obstructive sleep apnea.
AB  - Intraluminal airway pressure and pharyngeal muscle activity are widely recognized
      as major determinants of the size and collapsibility of the upper airway. In
      addition, changes in the volume or pressure of tissue surrounding the pharyngeal
      airway may significantly influence its size. The present study used fast computed
      tomography (CT) to determine the effects of changes in central venous pressure
      (CVP) on upper airway size. Ten awake male patients with obstructive sleep apnea
      (OSA) were studied. Scans were performed at functional residual capacity (FRC)
      and at the end of a tidal inspiration (VTei) under three conditions of CVP: (1)
      at baseline (CVP nl) with patients lying supine; (2) at decreased CVP (CVP-) by
      inflating blood pressure cuffs to 40 mm Hg on both legs; and (3) at increased CVP
      (CVP+) by elevating both legs to 33 degrees. At FRC, changes in CVP had no
      significant effect on either mean or minimum cross-sectional area (CSA) of the
      upper airway. In contrast, an analysis of variance (ANOVA) indicated that
      alterations in CVP were associated with changes in mean CSA (p = 0.03) and to a
      lesser extent in minimum CSA (p = 0.07) at VTei. With the legs elevated (CVP+),
      neither mean nor minimum CSA showed any significant change with tidal breathing.
      However, after leg-cuff inflation (CVP-), highly significant increases in both
      mean (163 +/- 22 to 218 +/- 19 mm2, p = 0.001) and minimum (48 +/- 8 to 85 +/- 12
      mm2, p = 0.02) CSA were detected. Changes in mean and minimum CSA with tidal
      breathing at baseline (CVP nl) were intermediate. These results indicate that
      changes in CVP significantly alter the response of the upper airway to tidal
      breathing. They further suggest that increases in upper airway size with tidal
      breathing may be related to reduction in venous blood volume in pharyngeal and
      neck tissues as the generation of negative intrathoracic pressure during
      inspiration increases venous return to the chest.

PMID- 8542125
TI  - Effects of mouth opening on upper airway collapsibility in normal sleeping
      subjects.
AB  - We investigated the influence of mouth opening on upper airway (UA)
      collapsibility in six healthy sleeping volunteers. UA collapsibility was measured
      during continuous negative airway pressure trials that consisted of the
      progressive decrease in pressure in a nasal mask, with simultaneous recording of
      esophageal pressure and instantaneous flow. Measurements were made under two
      experimental conditions: mouth closed (MC), and mouth open (MO). Cephalometric
      measurements were obtained with subjects awake in the same position for both
      experimental conditions. UA critical pressure (Pcrit) was derived from the
      relationship between the breath-by-breath values of the maximal inspiratory
      airflow and the corresponding mask pressure. Pcrit was significantly less
      negative during MO than during MC (MO, -12.7 +/- 4.8 cm H2O; MC, -16.4 +/- 6 cm
      H2O, mean +/- SD; p = 0.03). Mouth opening was associated with a significant
      increase in the total respiratory resistance (MO, 3.8 +/- 1.6 cm H2O/ml/s; MC,
      3.0 +/- 1.6 cm H2O/ml/s-1, p = 0.03). Besides an increase in the distance between
      the teeth and a reduction in the distance between the hyoid bone and the
      mandible, no significant changes in cephalometric parameters were found between
      MO and MC. We conclude that mouth opening increases UA collapsibility during
      sleep and that mouth opening may contribute to the occurrence of sleep-related
      breathing abnormalities.

PMID- 8542126
TI  - Nocturnal saturation improves by target-flow inspiratory muscle training in
      patients with COPD.
AB  - Nocturnal desaturations during rapid eye movement (REM) sleep, caused by
      nonobstructive hypoventilation, occur frequently in patients with chronic
      obstructive pulmonary disease (COPD). This is partly caused by decreased activity
      of the intercostal and accessory muscles due to a lower motor command. The
      diaphragm has to compensate for the diminished activity of these muscles during
      REM sleep. However, in patients with COPD strength and endurance of the diaphragm
      may be affected by its unfavorable position on the length-tension curve because
      of hyperinflation. The aim of this study was to establish the causal relationship
      between respiratory muscle function and nocturnal saturation in patients with
      COPD. We hypothesized that target-flow inspiratory muscle training (TF-IMT) would
      improve nocturnal saturation. In 20 patients with stable COPD (FEV1 35.5 +/-
      14.1% of predicted) and a mean nocturnal saturation below 92% we measured maximal
      inspiratory pressure (PImax), transdiaphragmatic pressure (Pdi), maximal
      sustainable inspiratory pressure (SIPmax), endurance time, and nocturnal
      saturation in Weeks 0, 4, and 10. During these 10 wk 10 patients underwent TF-IMT
      at 60% of PImax and 10 control patients received sham TF-IMT at 10% of PImax.
      PImax, Pdi, SIPmax, and the endurance time as well as the nocturnal saturation
      improved significantly in the 60% training group (by 3.0 +/- 1.5 kPa, 3.4 +/- 1.9
      kPa, 1.5 +/- 1.4 kPa, 189 +/- 149 s, and 1.9 +/- 2.2%, respectively), whereas no
      changes occurred in the sham training group. Also, significant correlations were
      observed between the changes in Pdi, SIPmax, and endurance time on the one hand
      and the change in nocturnal saturation on the other. We conclude that TF-IMT
      improves the nocturnal saturation in patients with severe COPD by increasing
      respiratory muscle strength and endurance.

PMID- 8542127
TI  - Effects of non-REM sleep on ventilation and respiratory mechanics in adults with
      cystic fibrosis.
AB  - To determine the effects of sleep upon respiratory function, five adult patients
      with cystic fibrosis (CF) were monitored during sleep in a horizontal body
      plethysmograph. Tidal volume (VT) decreased during non-rapid-eye-movement (NREM)
      sleep, resulting in a NREM sleep-associated decrement in minute ventilation (VI =
      11.10 +/- 0.67, 9.32 +/- 0.91, and 9.17 +/- 1.42 L during wakefulness, stage 2,
      and stages 3-4, respectively, p < 0.05). There were no NREM sleep-associated
      changes in respiratory frequency (f) or inspiratory time (Ti), but respiratory
      neuromuscular output was reduced during NREM sleep P0.1 = 3.33 +/- 0.57, 1.79 +/-
      0.23, and 1.99 +/- 0.21 cm H2O during wakefulness, stage 2, and stages 3-4,
      respectively, p = 0.005). Upper airway resistance (Rua), lower airway resistance
      (RIa), and lung volume did not change in association with NREM sleep. Functional
      residual capacity (FRC) measurements made using helium dilution indicated large
      volumes of trapped gas, likely a result of peripheral airways that were closed at
      FRC. We conclude that in adult patients with CF, NREM sleep is associated with a
      decrement in VT and VI, NREM sleep does not alter airflow resistance or lung
      volume, and the observed reductions in VT and VI apparently result from a NREM
      sleep-associated decrease in respiratory neuromuscular output.

PMID- 8542128
TI  - Increased mortality associated with Cheyne-Stokes respiration in patients with
      congestive heart failure.
AB  - We hypothesized that mortality is higher in patients with congestive heart
      failure (CHF) who develop Cheyne-Stokes respiration (CSR) during sleep than CHF
      patients without CSR. Overnight polysomnography was performed on 16 male patients
      with chronic, stable CHF: nine had CSR during sleep (CSR group) and seven did not
      (CHF group). The CSR group had a higher apnea-hypopnea index (AHI: 41 +/- 17
      versus 6 +/- 5/hr) and experienced greater sleep disruption. There were no
      significant intergroup differences between age, weight, cardiac function, and
      pulmonary function. After the initial sleep study, all patients were maintained
      on standard medical therapy for CHF without supplemental oxygen or nasal
      continuous positive airway pressure. Over the next 3.1 to 4.5 yr there was a
      significant difference between the number of deaths in each group. Five patients
      died in the CSR group and two received a heart transplant, whereas only one
      patient died in the CHF group. Regression analysis revealed that mortality was
      positively correlated with CSR, AHI, arousal index, and the amount of stage 1, 2
      non-REM sleep and was inversely related to the total sleep time. We conclude that
      mortality is higher in CHF patients who develop CSR during sleep than CHF
      patients without CSR. Although the development of CSR may simply reflect more
      severe cardiac impairment, we suggest that CSR itself accelerates the
      deterioration in cardiac function.

PMID- 8542129
TI  - CPAP improves inspiratory muscle strength in patients with heart failure and
      central sleep apnea.
AB  - Patients with congestive heart failure (CHF) suffer from respiratory muscle
      weakness which may contribute to dyspnea. Nasal continuous positive airway
      pressure (NCPAP) can improve left ventricular ejection fraction (LVEF) and reduce
      dyspnea in patients with CHF and Cheyne-Stokes respiration with central sleep
      apnea (CSR-CSA) but its effects on respiratory muscle strength are not known. We
      therefore studied the effects of NCPAP on maximal inspiratory and expiratory
      pressures (MIP and MEP, respectively), LVEF, dyspnea, and fatigue in patients
      with chronic CHF and CSR-CSA over 3 mo. Eight patients were randomized to control
      and nine to nightly NCPAP. There were no significant changes in any of these
      factors in the control group during the study. In contrast, among the NCPAP
      group, MIP increased from 79.3 +/- 8.1 to 90.7 +/- 10.4 cm H2O (mean +/- SEM; p <
      0.02), LVEF increased from 24.0 +/- 4.0 to 32.6 +/- 6.6% (p < 0.02) and symptoms
      of dyspnea and fatigue were alleviated. However, MEP did not change. In addition,
      the number of apneas and hypopneas decreased from 49 +/- 11 to 17 +/- 7 per hour
      of sleep (p < 0.001) and mean low Sao2 during sleep increased from 87.9 +/- 1.0
      to 93.0 +/- 1.0% (p < 0.01). Our data indicate that nightly application of NCPAP
      in patients with CHF and CSR-CSA improves inspiratory muscle strength and LVEF,
      and relieves dyspnea and fatigue.

PMID- 8542130
TI  - Arousal and cardiorespiratory responses to hypoxia in Prader-Willi syndrome.
AB  - Ventilatory responses to peripheral chemoreceptor stimuli are absent in patients
      with Prader-Willi syndrome (PWS) during wakefulness. Because arousal from sleep
      after rapidly developing hypoxia may require intact peripheral chemoreceptor
      function, we hypothesized that blunted hypoxic arousal responses during sleep
      Stage 3/4 would be present in PWS. Thirteen patients with PWS (mean age, 23.4 +/-
      3.7 +/- SEM yr; 46% male; body mass index [BMI], 28.9 +/- 1.6 kg/m2) and 11
      matched control subjects (mean age 28.0 +/- 5.4 yr; 54% male; BMI, 28.8 +/- 3.1
      kg/m2) were studied. An abrupt decrease in inspired O2 tension to 80 mm Hg was
      introduced until arousal occurred or for a maximum of 3 min. One of the 13
      patients with PWS and seven of the 11 control subjects were aroused by the
      hypoxic challenge (p < 0.02). During hypoxia, heart rate increased by 9 +/- 2% in
      the PWS group versus 22 +/- 4% in the control group (p < 0.005). Respiratory rate
      did not change in the PWS group (4 +/- 2%; p = NS), but it increased by 13 +/- 2%
      in the control group (p < 0.02). We conclude that abnormal arousal and
      cardiorespiratory responses to hypoxia are frequent in PWS. We postulate that
      intact peripheral chemoreceptor function is an important component underlying
      arousal mechanisms to rapidly developing hypoxia during sleep.

PMID- 8542131
TI  - Oxidative capacity of the skeletal muscle and lactic acid kinetics during
      exercise in normal subjects and in patients with COPD.
AB  - Early lactic acidosis during exercise and abnormal skeletal muscle function have
      been reported in chronic obstructive pulmonary disease (COPD) but a possible
      relationship between these two abnormalities has not been evaluated. The purpose
      of this study was to compare and correlate the increase in arterial lactic acid
      (La) during exercise and the oxidative capacity of the skeletal muscle in nine
      COPD patients (age = 62 +/- 5 yr, mean +/- SD, FEV1 40 +/- 9% of predicted) and
      in nine normal subjects of similar age (54 +/- 3 yr). Following a transcutaneous
      biopsy of the vastus laterialis, each subject performed a stepwise exercise test
      on an ergocycle up to his or her maximal capacity during which 5-breath averages
      of oxygen consumption (Vo2), and serial La concentration measurements were
      obtained. From the muscle biopsy specimen, the activity of two oxidative enzymes,
      citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH), and of three
      glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase
      were determined. The La/Vo2 relationship during exercise was fitted by an
      exponential function in the form La = a + bvo2, where be represents the shape of
      the relationship. The activity of the oxidative enzymes was significantly lower
      in COPD than in control subjects (22.8 +/- 3.3 versus 36.8 +/- 8.6 mumol/min/g
      muscle for CS, and 3.1 +/- 1.1 versus 5.5 +/- 1.4 mumol/min/g for HADH, p <
      0.0005) and the increase in lactic acid was steeper in COPD (b = 4.3 +/- 2.0
      versus 2.1 +/- 0.2 for normal subjects, p = 0.0005). A significant inverse
      relationship was found between CS, HADH, and b. No difference was found between
      the two groups for the glycolytic enzymes. We conclude that in COPD the increase
      in arterial La during exercise is excessive, the oxidative capacity of the
      skeletal muscle is reduced, and that these two results are interrelated.

PMID- 8542132
TI  - The daily energy expenditure in stable chronic obstructive pulmonary disease.
AB  - Resting energy expenditure is frequently increased in chronic obstructive
      pulmonary disease (COPD), but it is unknown if this hypermetabolism holds true
      over 24 h. The aim of this study was to measure the actual 24-h energy
      expenditure (24-h EE) in patients with stable COPD. Energy expenditure was
      measured by indirect calorimetry, using a metabolic chamber for 24-h EE and a
      canopy for basal metabolic rate (BMR). Physical activity was detected in the
      chamber by a radar system, and its duration was quantified. Two groups matched
      for age and height were studied: 16 male ambulatory patients with stable COPD and
      12 male normal subjects. Body weight was 92 +/- 12% of ideal body weight in the
      group with COPD and 108 +/- 11% in the control group (p = 0.01). BMR was 120 +/-
      7% of predicted in the group with COPD and 108 +/- 12% in the control group (p <
      0.01). However, 24-h EE was similar in the two groups, amounting to 1,935 +/- 259
      kcal in patients with COPD and 2,046 +/- 253 kcal in the control group (NS). This
      corresponded to 145% and 137% of predicted BMR, and to 121% and 126% of measured
      BMR in patients with COPD and the control group, respectively (NS). Patients were
      allowed to pursue their usual treatment within the chamber, and a positive
      correlation existed between 24-h EE and the daily dose of inhaled beta 2-agonists
      (p < 0.03). During daytime, physical activity was lower in patients with COPD.
      This study shows that patients with stable COPD are characterized by a normal
      daily energy expenditure in controlled conditions in spite of an increased basal
      metabolic rate. They appear to save energy by reducing their spontaneous level of
      physical activity.

PMID- 8542133
TI  - Health effects of outdoor air pollution. Committee of the Environmental and
      Occupational Health Assembly of the American Thoracic Society.
AB  - Particles, SOx, and acid aerosols are a complex group of distinct pollutants that
      have common sources and usually covary in concentration. During the past two
      decades, the chemical characteristics and the geographic distribution of sulfur
      oxide and particulate pollution have been altered by control strategies,
      specifically taller stacks for power plants, put in place in response to air
      pollution regulations adopted in the early 1970s. While the increasing stack
      heights have lowered local ambient levels, the residence time of SOx and
      particles in the air have been increased, thereby promoting transformation to
      various particulate sulfate compounds, including acidic sulfates. These sulfate
      particles constitute a large fraction of the total mass of smaller particles (< 3
      microns in aerodynamic diameter). Epidemiologic studies have consistently
      provided evidence of adverse health effects of these air pollutants. Particulate
      and SO2 pollution were strongly implicated in the acute morbidity and mortality
      associated with the severe pollution episodes in Donora (Pennsylvania), London,
      and New York in the 1940s, 1950s, and 1960s. There is new evidence that even
      current ambient levels of PM10 (30 to 150 micrograms/m3) are associated with
      increases in daily cardiorespiratory mortality and in total mortality, excluding
      accidental and suicide deaths. These associations have been shown in many
      different communities, as widely different in particle composition and climate as
      Philadelphia, St. Louis, Utah Valley, and Santa Clara County, California. It has
      recently been shown in a long-term prospective study of adults in the United
      States that chronic levels of higher PM10 pollution are associated with increased
      mortality after adjusting for several individual risk factors. Daily fluctuations
      in PM10 levels have also been shown to be related to acute respiratory hospital
      admissions in children, to school and kindergarten absences, to decrements in
      peak flow rates in normal children, and to increased medication use in children
      and adults with asthma. Although some epidemiologic studies suggest that acid
      aerosols are an important toxic component of PM10, other studies do not support
      this hypothesis. Dockery and Pope (408) recently reviewed the epidemiologic
      literature for adverse effects, assuming that reported associations can be
      attributed to acute particle mass exposures. Combined effects were estimated as
      percent increase in comparable measures of mortality and morbidity, associated
      with each 10 micrograms/m3 increase in daily mean PM10 exposure (Table 7). While
      total mortality increased by 1% for each 10 micrograms/m3 increase in PM10,
      respiratory mortality increased by 3.4% and cardiovascular mortality increased by
      1.4%. Hospital admissions and emergency department visits increased approximately
      1% for all respiratory complaints, and 2% to 3% for asthma. Exacerbation of
      asthma increased by about 3%, as did lower respiratory symptoms. Small decreases
      in lung function, approximately 0.1%, have also been observed. This review
      suggests that the epidemiologic studies of adverse morbidity measures are
      coherent with the mortality studies showing quantitatively similar adverse
      effects of acute exposures to particulate pollution. Despite these epidemiologic
      findings for acute and chronic adverse health effects from air pollution
      associated with relatively low levels of inhalable particles, there are no
      complementary data from toxicologic studies or from acute human exposures to
      similar levels of respirable particles. Thus, controlled human exposures to
      various particles, including H2SO4, at relevant levels (< 150 micrograms/m3) have
      not identified significant alterations in respiratory function in healthy
      individuals.(ABSTRACT TRUNCATED)

PMID- 8542134
TI  - Asbestos-related bilateral diffuse pleural thickening: natural history of
      radiographic and lung function abnormalities.
AB  - Sixty-four subjects with asbestos-related diffuse pleural thickening attending
      the London Medical Boarding Centre for Respiratory Diseases (formerly, the
      Central Pneumoconiosis Panel) were studied to investigate symptomatology, lung
      function, and radiographic change over an average period of 8 to 9 yr. Chest pain
      was a common symptom, occurring in over half of the subjects. Approximately one
      third of the subjects had a history of pleurisy or pleural effusion. Full long
      function, available in all cases, showed a highly significant decrement (p <
      0.001) compared with predicted values in all variables except gas transfer
      coefficient (Kco) at initial presentation, consistent with a restrictive
      ventilatory defect. Longitudinal lung function, available over a mean period of
      8.9 yr in 36 subjects, showed a significant decrement above that predicted in
      FEV1 and FVC only (p < 0.05). Decreases in other parameters were observed,
      although statistical significance was not achieved. Radiographic score increased
      with time but there was no correlation between change in lung function and
      increasing radiographic score, probably reflecting the initial severity of the
      disease in subjects studied. These observations confirm an initial decrement in
      lung function in diffuse pleural thickening which is followed by comparatively
      little change over time.

PMID- 8542135
TI  - Fucoidin, a potent inhibitor of leukocyte rolling, prevents neutrophil influx
      into phorbol-ester-induced inflammatory sites in rabbit lungs.
AB  - The polysaccharide fucoidin, a homopolymer of sulfated L-fucose, is known, by
      interfering with the function of L-selectin, to inhibit leukocyte rolling, which
      is an early and essential step in the process of leukocyte extravasation into
      inflamed sites. We tested the inhibitory effect of fucoidin on neutrophil
      accumulation in lung inflammation induced by phorbol myristate acetate and
      peritoneal inflammation induced by thioglycollate in rabbits. Pretreatment (10
      mg/kg) followed by continuous administration (10 mg/kg/h) of fucoidin
      dramatically reduced the number of neutrophils recruited into the lungs
      (determined by neutrophil counts in bronchoalveolar lavage fluid; 97.7 +/- 0.52%
      reduction) and peritoneal cavity (determined by neutrophil counts in peritoneal
      lavage fluid; 98.4 +/- 1.29% reduction). Fucoidin treatment also increased the
      systemic neutrophil count. These results suggest that the inhibition of leukocyte
      rolling, which may be a primary function of fucoidin, leads to a reduction of
      neutrophil accumulation at inflammatory sites, which may be beneficial for
      attenuating neutrophil-mediated tissue injury.

PMID- 8542136
TI  - Subcutaneous administration of hyaluronan reduces the number of infectious
      exacerbations in patients with chronic bronchitis.
AB  - Hyaluronan (HA) is a high molecular weight glycosaminoglycan found in large
      amounts in the skin, joints, and other organs. Previous studies have shown that
      HA stimulates neutrophil functions both in vitro and in vivo. The object of this
      study was to test the hypothesis that HA administration subcutaneously might
      reduce the number of bacterial infections in humans with an increased
      susceptibility to such infections. For this purpose we have studied 29 patients
      with chronic bronchitis and recurrent acute exacerbations of their disease. The
      patients were randomly separated into two groups. One group had HA for 6 mo
      followed by 6 mo of placebo, and the other group started with placebo treatment
      followed by HA. The treatment periods occurred during two consecutive winter
      periods. HA-treated patients had significantly fewer acute exacerbations (p =
      0.01) than did placebo-treated patients. Likewise the consumption of antibiotics
      and other signs of bacterial infections were reduced. In the crossover study the
      placebo-treated patients again had much higher numbers of acute exacerbations
      than did the HA-treated patients (p < 0.0001). It is concluded that HA reduces
      the number of infectious exacerbations in patients with chronic bronchitis,
      possibly by enhancing cellular host defense mechanisms. HA is a new endogenous
      substance that can be used to stimulate host defense reactions and reduce the
      need of antibiotics. Before being recommended for clinical use, however, our
      results should be confirmed by further studies.

PMID- 8542137
TI  - Outcome of MDR-TB patients, 1983-1993. Prolonged survival with appropriate
      therapy.
AB  - We analyzed the clinical and laboratory findings and outcome of 173 patients
      hospitalized at our institution from 1983 to 1994 with multidrug-resistant
      tuberculosis (MDR-TB) and evaluated outcome. The 173 patients (mean age 40 +/- 1
      yr) were predominantly male (92%), African American or Hispanic (80%), and mostly
      undomiciled. Over half (52%) were known to be HIV-infected. HIV-positive MDR-TB
      patients had significantly more pulmonary and constitutional symptoms, more
      extrapulmonary disease, and fewer cavitary lesions on chest radiographs. Fifty
      five percent of the patients in the cohort have died; mortality was significantly
      greater for HIV-positive than HIV-negative (72% versus 20%, p < 0.01). The median
      duration of survival of MDR-TB patients was 22 +/- 1 mo. Overall, extrapulmonary
      involvement was a risk factor for shorter survival, while a cavitary lesion on
      initial chest film and institution of appropriate treatment were positive
      predictors of survival. In HIV+ patients, only appropriate therapy was associated
      with prolonged survival (median of 14.1 mo). Interestingly, there was a trend
      toward better outcome in the first half of the decade reviewed. We conclude that
      although mortality from MDR-TB is high in both HIV-positive and HIV-negative
      patients, institution of appropriate therapy is the factor most strongly
      associated with a favorable outcome. Development of new diagnostic and
      therapeutic strategies for MDR-TB are urgently needed.

PMID- 8542138
TI  - Effect of sodium nitroprusside and diethylcarbamazine on hypoxic pulmonary
      vasoconstriction and regional distribution of pulmonary blood flow in
      experimental pneumonia.
AB  - The interaction between the effects of indomethacin and sodium nitroprusside or
      diethylcarbamazine infusion on the efficacy of hypoxic pulmonary vasoconstriction
      (HPV) and regional distribution of lung blood flow was studied in 15
      pentobarbital-anesthetized dogs with acute pneumonia caused by Pseudomonas
      aeruginosa. After induction of pneumonia central hemodynamics, gas exchange, and
      regional distribution of lung blood flow (radionuclide-labeled microsphere
      method) were measured during ventilation of both lungs with oxygen and again with
      one lung ventilated with nitrogen. The dogs were then randomly assigned to one of
      three treatment groups: Group I (n = 5) received indomethacin alone (2 mg/kg);
      Group I-D received indomethacin and diethylcarbamazine (50 mg/kg over 20 min
      followed by 1 mg/kg/min for the rest of the experiment); Group I-N (n = 5)
      received indomethacin with sodium nitroprusside to achieve a 20- to 30-mm Hg
      reduction in mean blood pressure. All measurements were then repeated during both
      oxygen ventilation and one-lung nitrogen ventilation. In all three groups there
      was no effect of nitrogen inhalation on distribution of lung blood flow prior to
      drug treatment, indicating absence of HPV. After treatment, in Group I, perfusion
      of the pneumonic lung fell from 0.27 +/- 0.08 to 0.10 +/- 0.03 (p < 0.05) of
      total lung blood flow, and nitrogen ventilation of the left lung reduced
      perfusion to that region from 0.23 +/- 0.02 to 0.13 +/- 0.02 (p < 0.05),
      indicating restoration of HPV. In Groups I-D and I-N, HPV was persistently absent
      or markedly attenuated after treatment, but the percentage of the cardiac output
      perfusing the pneumonia region fell by an amount similar to that in Group I (0.26
      +/- 0.07 to 0.11 +/- 0.04 in Group I-D and 0.35 +/- 0.03 to 0.21 +/- 0.06 in
      Group I-N, both p < 0.05). Because these two chemically unrelated pulmonary
      vasodilators effectively blocked HPV restoration but had no effect on
      vasoconstriction in the pneumonia region after indomethacin, it is concluded that
      regional lung blood flow redistribution in pneumonia is mediated by a mechanism
      other than HPV.

PMID- 8542139
TI  - Transmission of tuberculosis to close contacts of patients with multidrug
      resistant tuberculosis.
AB  - Multidrug-resistant tuberculosis (MDRTB) has emerged as a major public health
      problem worldwide. To determine the incidence and risk factors associated with
      tuberculosis among contacts of MDRTB index cases, we studied human
      immunodeficiency virus-seronegative close contacts of 64 culture-confirmed MDRTB
      patients in Rio de Janeiro, Brazil. Between March 1988 and July 1992,
      tuberculosis developed in 17 (7.8%) of 218 previously healthy close contacts of
      64 MDRTB index cases (1.6 cases per 1,000-person-months of contact). Among
      strains of Mycobacterium tuberculosis isolated from 13 contacts of 12 index
      cases, six (46%) had susceptibility patterns identical to those of their index
      cases, four (31%) had different patterns of resistance, and three (23%) were
      susceptible to all drugs. Tuberculosis developed more frequently in male contacts
      (p < 0.05), persons > or = 15 yr of age (p < 0.05), nonwhites (p < 0.001), and
      persons not previously vaccinated with bacillus Calmette-Guerin (BCG) (p < 0.05).
      The association of BCG vaccination with decreased risk of disease was significant
      even when this variable was controlled (by Cox's regression analysis) for age,
      sex, race, purified protein derivative (PPD) status, and isoniazid prophylaxis.
      BCG vaccination appears to offer protection against tuberculosis during prolonged
      exposures to persons with MDRTB, which identifies a novel and specific indication
      of BCG use.

PMID- 8542140
TI  - Compartmentalized IL-8 and elastase release within the human lung in unilateral
      pneumonia.
AB  - Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating
      cytokine, we investigated IL-8 production in relation to neutrophil migration and
      elastase release in the human lung during unilateral community-acquired pneumonia
      (CAP). In 17 patients, the local response in the involved lung was compared with
      that in the contralateral, noninvolved lung, and with the systemic response.
      Eight healthy volunteers served as controls. IL-8, total neutrophil elastase
      (NE), free elastase activity, alpha 1-antitrypsin (alpha 1-AT), and total
      leukocyte and neutrophil counts were evaluated in bronchoalveolar lavage fluids
      (BALF). Mean IL-8 concentrations in BALF from the involved lungs of the patients
      were significantly greater than those in BALF from the noninvolved lung or from
      controls (p < or = 0.001). By contrast, the serum IL-8 concentration was not
      different in patients and in controls. Total NE and alpha 1-AT concentrations
      were increased in BALF from the involved lung as compared with the noninvolved
      lung or controls (p < or = 0.001). The elastase-inhibitory capacity of alpha 1-AT
      in BALF was impaired in the involved lung of seven of the 14 patients as compared
      with the controls, leading to free elastase activity in the involved lung of all
      patients with CAP. Plasma total NE concentrations were significantly greater in
      the CAP patients than in the controls. IL-8 concentrations in BALF correlated
      positively with total leukocyte counts, absolute numbers and percentages of
      neutrophils, total NE concentrations, and free elastase activity. Our results
      suggest that during unilateral CAP, locally produced IL-8 may trigger neutrophil
      accumulation and activation, thus contributing to a local elastase/antielastase
      imbalance within the site of infection.

PMID- 8542141
TI  - Pneumonia in intubated trauma patients. Microbiology and outcomes.
AB  - To describe the epidemiology of nosocomial pneumonia in trauma patients and its
      impact on outcome, we performed a retrospective case-control analysis.
      Quantitative bronchoscopic cultures were collected from 62 intubated patients
      with suspected pneumonia. Patients with proven pneumonia had higher abdominal
      injury scores. Those with bronchoscopy-negative pneumonitis were older. Age and
      injury severity were used to match two controls to each case. The incidence of
      pneumonia was 5.8% Streptococci and Hemophilus were common pathogens, but gram
      negative rods were isolated more frequently after lengthier intubation.
      Polymicrobial infections were common. There were no serious complications of
      bronchoscopy, and culture results often led to antibiotic therapy. No excess
      mortality could be attributed to pneumonia. Patients with pneumonia and those
      with bronchoscopy-negative pneumonitis required prolonged care compared with
      others (p < 0.05). Patients with pneumonia did not receive excess ventilation or
      hospitalization but incurred hospital charges 1.5 times higher than controls (p =
      0.04). Pneumonia was confirmed in less than half of those suspected of having it
      on the basis of clinical findings. When severity of injury was considered,
      pneumonia was associated with neither increased mortality nor increased hospital
      care, but the clinical features suggesting respiratory infection identified
      trauma patients requiring prolonged hospitalization and incurring higher costs.

PMID- 8542142
TI  - Interleukin-3 in bronchial biopsies from nonasthmatics and patients with mild and
      allergen-induced asthma.
AB  - Cytokines, such as interleukin-3 (IL-3), have been suggested to play an important
      role in mediating the increased number of airway eosinophils and metachromatic
      cells in patients with even mild asthma. We used immunohistochemistry to
      determine the presence of IL-3 protein in bronchial biopsies from nonasthmatics
      (n = 10) and subjects with mild (n = 8) and allergen-induced (n = 7) asthma. We
      also examined whether IL-3 was related to airway eosinophil number and
      activation, the number of airway metachromatic cells, or airway function. We
      found that the number and activation of eosinophils and the number of
      metachromatic cells were increased in the airways of asthmatics, compared with
      nonasthmatics, with further increases evident after allergen challenge. IL-3
      protein was localized primarily to the epithelium in nonasthmatic and asthmatic
      subjects, with no difference apparent between groups or after allergen inhalation
      challenge. The extent of staining for IL-3 in the tissue was not correlated with
      eosinophil number or activity, metachromatic cell number, airway responsiveness,
      or the severity of the late asthmatic response. This study provides the first
      demonstration of IL-3 protein localization in bronchial tissue from human
      airways. The results suggest that the increases in eosinophils and metachromatic
      cells associated with mild and allergen-induced asthma occur independent of IL-3.

PMID- 8542143
TI  - Airways responsiveness, wheeze onset, and recurrent asthma episodes in young
      adolescents. The East Boston Childhood Respiratory Disease Cohort.
AB  - To describe the role of airways responsiveness in predicting incidence of wheeze
      in early adolescence and to examine the association between airways
      responsiveness and active asthma symptoms, children who had been tested for
      airways hyperresponsiveness were assessed prospectively. Of 770 children in the
      East Boston Childhood Respiratory Disease Cohort who were between 5 and 9 yr of
      age at time of entry into the study, 281 children received airways challenges
      during voluntary follow-up conducted between 1980 and 1986. Each subject
      presented a sequence of wheeze or asthma diagnosis reports along with a sequence
      of time-varying covariates, including airways challenge results and symptom and
      exposure information. A robust "pooled repeated observations" analog of the
      proportional hazard regression model was used to assess associations among risk
      factors and the probability of incident wheeze or active asthma. In the analysis
      of wheeze incidence, airways responsiveness (elicited via eucapnic
      hyperventilation with cold air or methacholine challenge) among those free of a
      history of wheeze at a given visit was found to be associated with a greater
      tendency to develop wheezing in the next visit (odds ratio [OR] = 3.91, 95%
      confidence interval [CI] = 1.21, 12.66), after controlling for a constellation of
      known risk factors. In the analysis of recurrent asthma episodes, airways
      responsiveness at a given visit was associated with a greater tendency to have an
      asthma diagnosis reported at the subsequent visit (OR = 4.2, 95% CI = 1.92,
      9.23). For subjects presenting multiple airways responsiveness challenge studies,
      two successive positive airways responsiveness results were independently
      associated with a higher likelihood of recurrent asthma episodes. These results
      confirm the predictive importance of airways responsiveness in the natural
      history of the development and persistence of asthmatic symptoms.

PMID- 8542144
TI  - Quantitative assessment of the epithelial and inflammatory cell populations in
      large airways of normals and individuals with cystic fibrosis.
AB  - Nasal and bronchial brushings and bronchial biopsies were evaluated from patients
      with cystic fibrosis (CF) and from normal subjects to quantify epithelial and
      inflammatory cell types. Epithelial in both groups were dominated by ciliated
      cells. The relative proportions of epithelial cells recovered by brushing and
      biopsy were similar, but with more basal cells from biopsies than from brushings.
      In nasal brushings, the numbers and percentages of epithelial subtypes were
      similar in both groups. In bronchial brushings, the number of recovered cells was
      2.5-fold increased in the CF group compared with that in the normal group because
      of large numbers of neutrophils. The proportion of ciliated cells was lower in
      the CF group than in the normal group. Thus, even though the CF transmembrane
      conductance regulator mutations are expressed similarly in the nasal and
      bronchial epithelium in CF, the consequences are different, with little
      inflammation and no changes in the proportions of epithelial cells in the nasal
      epithelium, compared with marked neutrophil inflammation on the epithelial
      surface and significant changes in epithelial populations in the large airways.
      Airway brushing permits repetitive evaluation of the airway epithelium in CF, a
      useful methodology in the assessment of new therapies for this disorder.

PMID- 8542145
TI  - Administration of truncated secretory leukoprotease inhibitor ameliorates
      bleomycin-induced pulmonary fibrosis in hamsters.
AB  - The purposes of this study were to investigate the effect of our recently
      developed truncated secretory leukoprotease inhibitor (SLPI) on bleomycin (BLM)
      induced lung injury and fibrosis in hamsters, which is widely used as a model of
      interstitial pulmonary fibrosis, and to assess the possible involvement of
      neutrophil elastase in the pathogenesis of pulmonary fibrosis. The fibrosis model
      was prepared by administration of BLM (10 mg/kg) intratracheally to hamsters. The
      truncated SLPI was administered at a dose 5 or 15 mg/kg intraperitoneally twice a
      day only for 10 d starting from the time of BLM administration. BLM
      administration resulted in decreases in body weight and survival rate. Elastase
      activity in the supernatant of bronchoalveolar lavage (BAL) fluids was increased
      at 3 and 7 d after BLM administration in parallel with the increase in the number
      of neutrophils in the fluids. Histopathologically, at 14 and 28 d after BLM
      administration, diffuse thickening and fibrosis of alveolar walls with marked
      cell infiltration and severe distortion of alveolar structure, including
      honeycomb lung, were observed to have occurred. In this model, the decreases in
      body weight and survival rate and the increase in elastase activity were
      inhibited by the truncated SLPI dose-dependently, and pulmonary fibrosis was
      significantly ameliorated by the administration of this shortened form of SLPI.
      These results suggest that neutrophil elastase may be implicated in the
      pathogenesis of BLM-induced pulmonary fibrosis and that the truncated SLPI might
      be a promising therapeutic in the treatment of interstitial pulmonary fibrosis.

PMID- 8542146
TI  - Assessment of mycobacterial DNA in cells and tissues of mycobacterial and sarcoid
      lesions.
AB  - In this study we applied a polymerase chain reaction (PCR) assay for the
      detection and species-specific identification of mycobacteria to samples from
      patients with sarcoidosis and mycobacterial infections and from control patients.
      The PCR-technique is based on the amplification of mycobacterial DNA coding for
      16S rRNA, which is present in all mycobacterial species, and on the additional
      sequencing of the PCR fragment to determine the species. Mycobacterial DNA could
      be detected in lung tissues and bronchoalveolar lavage cells from cases of
      tuberculosis and infections with atypical mycobacteria. On the other hand,
      mycobacterial DNA was amplified only in lung tissue from one patient with
      sarcoidosis. Twenty-three samples from patients with sarcoidosis were negative
      for mycobacterial DNA. From our results we conclude that the granulomatous
      lesions in sarcoidosis may not be due to mycobacterial infections.

PMID- 8542147
TI  - Airway responsiveness to bradykinin is related to eosinophilic inflammation in
      asthma.
AB  - We investigated the relationship between airway inflammation and airway
      responsiveness, as assessed by PD15, to methacholine and to bradykinin in
      asthmatic patients. Bronchoalveolar lavage (BAL), bronchial biopsies, and
      methacholine and bradykinin challenges were performed in 18 nonsmoking subjects
      with mild or moderate perennial asthma. Bradykinin PD15 correlated negatively
      with eosinophil count in BAL (p < 0.05), in the epithelium (p < 0.05), in the
      lamina propria (p = 0.02) and in the total submucosa (p < 0.01). Conversely, no
      significant correlation existed between airway responsiveness to methacholine and
      eosinophil count in BAL or in airway mucosa. Airway responsiveness to either
      agonist did not correlate with the thickness of the basement membrane, the
      shedding of the airway epithelium, the count of lymphocytes in the airway mucosa,
      or the percentage of neutrophils, lymphocytes, and macrophage in BAL. The
      presence of degranulated eosinophils was associated with an increased number of
      eosinophils in the airway epithelium (p = 0.04), in the lamina propria (p =
      0.03), in the total submucosa (p = 0.02), and with increased airway
      responsiveness to bradykinin (p < 0.02). We conclude that in asthmatic patients,
      airway responsiveness to bradykinin but not to methacholine is related to the
      magnitude of eosinophilic inflammation in the airway mucosa.

PMID- 8542148
TI  - Effect of a specific neutrophil elastase inhibitor, ONO-5046, on endotoxin
      induced acute lung injury.
AB  - Because excessive neutrophil elastase (NE) activity is involved in the
      pathogenesis of acute lung injury, we speculated that administering anti-NE might
      prevent lung injury. In a guinea pig model of acute lung injury induced by
      Escherichia coli endotoxin (lipopolysaccharide [LPS]), we investigated the effect
      of ONO-5046, a low-molecular-weight and specific inhibitor of NE. ONO-5046
      produced concentration-dependent inhibition of guinea pig NE, whereas there were
      no inhibitory effects on neutrophil chemotaxis or the expression of adhesion
      molecules in endothelial cells. Detectable NE activity in bronchoalveolar lavage
      (BAL) fluid was present in the LPS-alone group. No NE activity in BAL fluid was
      detected in the LPS+ONO-5046 groups. Neutrophil counts in BAL fluid, the lung
      tissue wet to dry weight ratio, and the lung tissue or BAL fluid to plasma ratio
      of 125I-albumin were increased in the LPS-alone group as compared with the saline
      group (p < 0.05). In the LPS+ONO-5046 group, neutrophil counts in BAL fluid, the
      lung tissue wet to dry weight ratio and BAL fluid to plasma ratio of 125I-albumin
      were decreased as compared with the LPS-alone group (p < 0.05). These data
      suggest that ONO-5046 can attenuate LPS-induced acute lung injury.

PMID- 8542149
TI  - Surfactant subfractions during nosocomial infection in ventilated preterm human
      neonates.
AB  - Long after resolution of the neonatal respiratory distress syndrome,
      deterioration of respiratory function in ventilated premature infants during
      severe nosocomial infections is commonly observed. Based on an increased oxygen
      demand and ventilatory support, impairment of the pulmonary surfactant system was
      hypothesized to occur. The clinical course of 10 premature neonates (764 +/- 57
      g, 26.6 +/- 0.4 wk) with nosocomial infection mainly due to Staphylococcus
      epidermidis was divided into four periods in each individual patient: "before
      deterioration" (average 8 to 11 d of life), "deterioration" (11 to 17 d), "peak"
      (17 to 22 d), and "recovery" (22 to 24 d). A total of 810 airway specimens were
      obtained by small volume lavage (1 ml/kg bw), pooled to yield appropriate amounts
      for differential centrifugation into two distinct subfractions known as large
      surfactant aggregates (LA) and small surfactant aggregates (SA). "Before
      deterioration" the amount of phospholipids recovered was constant, and the two
      fractions were characterized by electron microscopic morphology and biochemical
      analysis. In the LA fraction lamellar body-like lipid structures were
      demonstrated, and the phospholipid composition was typical of pulmonary
      surfactant in premature neonates with a high content of phosphatidylcholine and
      phosphatidylinositol. With "deterioration" and "peak" the masses of total
      phospholipids and of phosphatidylcholine recovered were reduced (p < 0.05). At
      the same time the mass ratio of SA/LA for phosphatidylcholine decreased from 0.32
      +/- 0.10 to 0.18 +/- 0.03, indicating a more pronounced decrease of the SA
      fraction (p < 0.05). The phospholipid composition in the LA fraction did not
      change during the course of nosocomial infection. In the SA fraction a decrease
      of phosphatidylcholine and a concomitant increase in lysophosphatidylcholine were
      observed at the "peak" of the infection. We concluded that, in ventilated
      premature neonates during nosocomial infection and respiratory deterioration,
      changes in phospholipid subfractions occur, possibly indicating impairment of
      pulmonary surfactant metabolism. These findings may be important when considering
      treatment of acute lung injury with nebulized exogenous surfactant.

PMID- 8542150
TI  - The efficacy and safety of KL4-surfactant in preterm infants with respiratory
      distress syndrome.
AB  - The present study was undertaken to determine if a synthetic peptide,
      KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous
      dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and
      improve gas exchange in premature human infants with respiratory distress
      syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid
      pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated
      within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4
      Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39
      patients included in efficacy analyses rose from pretreatment values of 0.14 +/-
      0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age.
      Mean airway pressures and oxygenation index values fell concomitantly, and
      expansion of the lungs was observed on radiographs. The median duration of
      mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a
      single dose. Radiographic data indicate that those patients requiring a second
      instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios
      did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related
      deaths; the incidence of complications was no higher than found in other
      comparable published studies. The data demonstrate that the synthetic peptide,
      KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when
      formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates
      a strong and durable surfactant activity as judged by expansion of pulmonary
      alveoli and improvement of gas exchange in infants with RDS.

PMID- 8542151
TI  - P53 in squamous metaplasia: a marker for risk of respiratory tract carcinoma.
AB  - Dysplasia in squamous metaplasia of the respiratory tract was believed to be a
      reversible premalignant lesion. Recently, presumably irreversible genetic
      alterations have been demonstrated in squamous metaplasia with dysplasia in lung
      resection specimens. The genetic alterations were closely similar to those in
      adjacent bronchial carcinoma. There remains the question of which changes in
      squamous metaplastic lesions are premalignant, and which of these changes predict
      the occurrence of carcinoma of the respiratory tract. The purpose of this study
      was to determine the positive predictive value for respiratory-tract malignancy
      of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl
      2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial
      biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993
      were used. Immunohistochemistry was done after microwave pretreatment of the
      biopsy specimens. Only unequivocally stained nuclei were counted. Normal
      bronchial epithelium obtained from autopsies was used as a control. In 31
      patients, a synchronous or metachronous carcinoma was present (61%). Positive p53
      immunoreactivity was found in 22 of the 51 patients (43%). The positive
      predictive values of p53 and of a high grade of dysplasia for carcinoma of the
      respiratory tract were 91% and 80%, respectively. Although the hyperproliferative
      state of squamous metaplastic lesions was clearly established, neither the
      percentage of MIB-1 labelling nor the mitotic index distinguished patient groups
      with and without carcinoma. No increased Bcl-2 immunostaining was found in
      squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic
      lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.

PMID- 8542152
TI  - Fluorodeoxyglucose-positron emission tomography in the detection and staging of
      lung cancer.
AB  - Glycolysis is increased in tumor tissues. [18F]fluoro-2-deoxy-D-glucose (FDG) is
      a glucose analogue radiopharmaceutical used in positron emission tomography (PET)
      to trace glucose metabolism. We investigated the sensitivity and specificity of
      FDG-PET imaging in the diagnosis and staging of lung cancer. One hundred and
      seven patients who had abnormal chest roentgenograms underwent whole-body PET
      imaging using FDG. PET scan results were classified as positive or negative based
      on the presence or absence of increased FDG uptake in the lung and/or in the
      mediastinum. All 82 patients with lung cancer had increased FDG uptake in the
      lungs, whereas only 12 of 25 patients with nonmalignant diseases had increased
      FDG uptake. Sixteen lung cancer patients with mediastinal metastases had
      increased FDG uptake in the mediastinum, of whom three had no lymphadenopathy on
      computed tomography of the chest. Sixteen lung cancer patients without
      mediastinal nodal involvement had no FDG uptake in the mediastinum. Seven of
      these patients had lymphadenopathy on computed tomography. FDG-PET imaging is
      100% accurate in predicting mediastinal involvement in patients with lung cancer.
      It is 100% sensitive and 52% specific in predicting the malignant nature of a
      chest radiographic abnormality.

PMID- 8542153
TI  - Sternomastoid muscle size and strength in patients with severe chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) imposes a major strain on the
      respiratory muscle pump, and it is conventionally thought that the inspiratory
      muscles of the neck adapt to this chronic overload by developing hypertrophy. Yet
      previous anthropometric studies have shown atrophy of the sternomastoid muscles.
      To solve this discrepancy, we have measured the cross-sectional area of these
      muscles by computed tomography. Ten stable patients with severe airflow
      obstruction (FEV1 = 0.76 +/- 0.12 L) and hyperinflation (FRC = 210 +/- 29% of
      predicted) and 10 control subjects matched for age, sex, and height were studied.
      The sternomastoid cross-sectional area in the patients averaged (mean +/- SD)
      4.29 +/- 1.48 cm2, and that in the control subjects was 3.96 +/- 0.82 cm2. This
      small difference could be entirely accounted for by hyperinflation, and it was
      not statistically significant. Sternomastoid muscle torque in patients was also
      similar to that in the control subjects. In patients with severe COPD, therefore,
      the sternomastoid muscles are essentially normal. As a corollary, their frequent
      prominence on clinical examination is only apparent.

PMID- 8542154
TI  - Pulmonary histiocytosis X: pulmonary function and exercise pathophysiology.
AB  - Pulmonary histiocytosis X (PHX) is a diffuse, smoking-related lung disease
      characterized pathologically by bronchocentric inflammation, cyst formation, and
      widespread vascular abnormalities and physiologically by exercise limitation. The
      major mechanism underlying exercise impairment in this disease has not been
      previously defined. Spirometry, lung volumes, lung mechanics, and exercise
      physiology were performed on 23 patients with PHX. Two subgroups were identified
      on the basis of elastic recoil: 12 subjects had an elevated coefficient of
      elastic recoil with 11 demonstrating a predominant pattern of restriction, and 10
      subjects had normal elastic recoil and relatively normal lung function. Exercise
      performance was severely limited in both subgroups (workload 53 +/- 3%).
      Abnormalities of ventilatory function and gas exchange were present but did not
      appear to be exercise-limiting in the majority of subjects. Indices reflecting
      pulmonary vascular function (DLCO, baseline VD/VT, exercise VD/VT) were abnormal.
      Strong correlations between overall exercise performance (% predicted VO2max) and
      indices of vascular involvement were present: DLCO (r = 0.68, p = 0.0004),
      baseline VD/VT (-0.65, 0.001), exercise VD/VT (-0.67, 0.0004). Similar
      correlations were found when exercise performance was measured by maximal
      workload achieved. We conclude that (1) subjects with PHX present with either
      normal or predominantly restrictive pulmonary physiology and that (2) exercise
      impairment is common and appears to reflect pulmonary vascular dysfunction.

PMID- 8542155
TI  - Neonatal capsaicin treatment increases the severity of ozone-induced lung injury.
AB  - To test the hypothesis that lung sensory C fibers protect the small distal
      airways and alveoli from oxidant injury, we compared the effects of inhalation of
      ozone (1 ppm) or filtered air for 8 h on lung injury and lung inflammation in
      four groups of rats: (1) normal rats exposed to filtered air; (2) normal rats
      exposed to ozone; (3) rats treated as neonates with capsaicin (50 mg/kg,
      intraperitoneally) and subsequently exposed to filtered air; and (4) rats treated
      as neonates with capsaicin and subsequently exposed to ozone. All rats were
      allowed to recover in filtered air for 0, 4, 16, and 40 h before necropsy. Rats
      exposed to filtered air (Groups 1 and 3) showed normal airway and parenchyma
      structure. Normal untreated rats exposed to ozone showed a random distribution of
      mild, interstitial inflammatory changes and epithelial necrosis of bronchi and
      bronchiolar epithelium. However, rats treated with capsaicin and subsequently
      exposed to ozone demonstrated severe acute interstitial inflammation and
      epithelial coagulate necrosis in all airways, especially in small, peripheral
      airways and parenchyma; all of these changes were statistically significant.
      These findings support our hypothesis that lung sensory C fibers protect the
      distal airways from oxidant injury during acute ozone inhalation.

PMID- 8542156
TI  - Black spots concentrate oncogenic asbestos fibers in the parietal pleura.
      Thoracoscopic and mineralogic study.
AB  - Epidemiologic and pathologic data demonstrate that malignant mesothelioma occurs
      preferentially after exposure to long amphibole asbestos fibers. However,
      mineralogic studies have rarely detected such fibers in the parietal pleura. We
      hypothesized that the distribution of asbestos fibers in the pleura was
      heterogeneous and that they might concentrate in certain areas, as does coal dust
      in patients showing anthracotic "black spots" of the parietal pleura during
      thoracoscopy. We collected thoracoscopic biopsy samples from these black spots
      and from normal areas of the parietal pleura and lung from 14 subjects (eight
      with and six without asbestos exposure). Asbestos content was determined by
      transmission electron microscopy. In exposed subjects, mean fiber concentrations
      were 12.4 +/- 9.8 x 10(6) fibers/g of dry tissue in lung, 4.1 +/- 1.9 in black
      spots, and 0.5 +/- 0.2 in normal pleura. In unexposed patients, concentrations
      were 0, 0.3 +/- 0.1, and 0, respectively. Amphiboles outnumbered chrysotile in
      all samples. A total of 22.5% of fibers were > or = 5 microns in length in black
      spots. A histologic similarity of these black spots with milky spots is suggested
      by conventional and electron microscopy. We conclude that the distribution of
      asbestos fibers is heterogeneous in the parietal pleura. Indeed, the fibers
      concentrate in black spots, where they can reach high concentrations. These
      findings could explain why the parietal pleura is the target organ for
      mesothelioma and plaques.

PMID- 8542157
TI  - Polyarteritis nodosa with pulmonary vasculitis.
AB  - Although early postmortem series reported pulmonary involvement as a relatively
      common manifestation of polyarteritis nodosa (PAN), using the modern
      classification of PAN pulmonary involvement is very uncommon. A 62-yr-old male
      with well-documented classic PAN was found to have an arteritis of medium-sized
      muscular pulmonary arteries. The patient subsequently demonstrated a complete
      response to treatment. Of the few reported cases of PAN with pulmonary
      manifestations, the majority are autopsy series and the vascular lesion involves
      the bronchial arteries. There are no case reports of patients with pulmonary
      involvement of PAN who responded successfully to treatment. This case is the
      first description of a premortum diagnosis of pulmonary arteritis in PAN in which
      the patient had a response to treatment.

PMID- 8542158
TI  - Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic
      patients.
AB  - Exhaled nitric oxide (NO) is elevated in untreated patients with asthma but not
      in patients treated with inhaled glucocorticoids. This may reflect an inhibitory
      effect of glucocorticoids on the induction of the enzyme NO synthase in the
      respiratory tract. We have now studied the effect of an inhaled glucocorticoid
      (budesonide 800 micrograms twice daily via a dry powder delivery system for 3 wk)
      on exhaled NO in 11 patients with mild asthma in a double-blind crossover
      randomized-order placebo-controlled study. Exhaled NO was reduced from a baseline
      value of 203 +/- 29 parts per billion (ppb) to 120 +/- 26 ppb after 3 wk of
      treatment (p < 0.01), whereas there was no change after a matched placebo (169 +/
      20 at baseline compared with 184 +/- 16 ppb after 3 wk). A significant and
      progressive fall in exhaled NO was found from 1 to 3 wk. There was no significant
      change in FEV1 after inhaled steroids (although mean FEV1 was 92% predicted
      normal at baseline), although there was a reduction in airway responsiveness to
      methacholine (approximately 2.5 doubling dilutions). These results add further
      support to the view that the elevated levels of exhaled NO in asthma may derive
      from induction of an inducible isoform of NO synthase and indicate that exhaled
      NO may be a useful way of monitoring the anti-inflammatory effects of
      glucocorticoids and other anti-inflammatory treatments in asthma.

PMID- 8542159
TI  - Effects of laparoscopic cholecystectomy on global respiratory muscle strength.
AB  - Laparoscopic cholecystectomy has a better postoperative outcome than the
      traditional open technique, which has been shown to significantly affect
      respiratory muscle function. The aim of this study was to investigate the effects
      of laparoscopic surgery on respiratory function, and particularly that of the
      respiratory muscles. Respiratory muscle strength was assessed in 26 patients who
      underwent laparoscopic cholecystectomy and in 25 who underwent open
      cholecystectomy by measuring mouth pressure during maximum static inspiratory
      (PImax) and expiratory (PEmax) efforts. PImax, PEmax, and blood gases were
      measured 24 h preoperatively (-24 h) as well as 24 h (+24 h) and 48 h (+48 h)
      postoperatively. FEV1 and FVC were measured at -24 h and +48 hr, and the ratio of
      FEV1 to FVC (FEV1/FVC) was calculated. PImax decreased at +24 h and +48 h in both
      groups, but this decrease was significantly greater in the patients who had open
      surgery, (p < 0.01, and p < 0.005, respectively). Similarly, PEmax was
      significantly smaller in the open- than in the laparoscopic-surgery group (p <
      0.0001) at +48 h. Spirometric indices showed a more severe restrictive defect at
      +48 h after open surgery than after laparoscopy (p = 0.01). The arterial oxygen
      tension (PaO2) was significantly greater in the laparoscopic- than in the open
      surgery group at +24 h (p < 0.007). Laparoscopic cholecystectomy caused smaller
      decreases in respiratory muscle strength than did open surgery. This accords with
      the hypothesis of phrenic nerve inhibition during open surgery. The results are
      of clinical importance, since they may explain the different outcomes with the
      two techniques.

PMID- 8542160
TI  - SAPALDIA Study. Swiss study on Air Pollution and Respiratory Diseases in Adults.

PMID- 8542161
TI  - Colonization in patients receiving and not receiving topical antimicrobial
      prophylaxis.

PMID- 8542162
TI  - Effects of overnight supplemental oxygen in obstructive sleep apnea in children.
AB  - Supplemental oxygen during sleep may be useful as a temporary palliative
      treatment in children with obstructive sleep apnea syndrome (OSAS) associated
      with significant hypoxemia. However, supplemental O2 may also blunt hypoxic
      ventilatory drive and worsen ventilation. To assess the safety of the use of
      supplemental O2 in children with OSAS, we studied 16 children ages 2-8 (mean:
      4.28 +/- 2.88 yr) with OSAS secondary to adenotonsillar hypertrophy. Patients
      underwent two overnight polysomnograms within 1 mo, one on room air (RA) and one
      while receiving supplemental O2 via nasal cannula titrated by 1/4 lpm increments
      to achieve SpO2 > 95% during the first hour of sleep. Oxygenation measurements
      were significantly improved during supplemental O2 nights (average SpO2 increased
      from 89.5 +/- 4.8% on RA to 97.7 +/- 1.8% on supplemental O2 [p < 0.00001]) while
      alveolar ventilation remained unchanged (PETCO2 > 50 mm Hg: 3.6 +/- 8.9% total
      sleep time on RA and 3.3 +/- 6.3% total sleep time on supplemental O2 [p = NS]).
      Supplemental O2 significantly reduced hypopnea density, obstructive apnea index,
      and paradoxical breathing. The density and average duration of central apneas
      remained unchanged. In addition, supplemental O2 increased the percentage of REM
      sleep time and decreased the number of microarousals. We conclude that
      supplemental O2 might be a safe and beneficial temporary treatment in children
      with OSAS.

PMID- 8542163
TI  - The effect of ozone exposure on allergen responsiveness in subjects with asthma
      or rhinitis.
AB  - The aim of this study was to determine whether ozone enhances bronchial
      responsiveness to allergens in subjects with allergic asthma, or facilitates a
      bronchial response in subjects with allergic rhinitis. Twenty-four subjects with
      mild stable allergic asthma, 12 subjects with allergic rhinitis without asthma,
      and 10 healthy subjects participated in the study. Subjects breathed 250 ppb
      ozone or filtered air (FA) for 3 h of intermittent exercise. Airway
      responsiveness to methacholine was determined 1 h before and after exposures, and
      allergen responsiveness 3 h after exposures. We determined the concentration of
      methacholine (PC20FEV1) and the dose of allergen (PD20FEV1) producing a 20% fall
      in FEV1. In the subjects with asthma, FEV1 decreased by 12.5 +/- 2.2% (mean +/-
      SEM; p = 0.0001), PC20FEV1 of methacholine by 0.91 +/- 0.19 doubling
      concentrations (p = 0.0001) and PD20FEV1 of allergen by 1.74 +/- 0.25 doubling
      doses (p < 0.0001) after ozone compared with FA. The changes in lung function,
      methacholine, and allergen responsiveness did not correlate with each other. In
      the subjects with rhinitis, mean FEV1 decreased by 7.8% and 1.3% when ozone or
      FA, respectively, were followed by allergen inhalation (p = 0.035). Therefore,
      our data suggest that short-term exposure to ozone can increase bronchial
      allergen responsiveness in subjects with mild allergic asthma or rhinitis.

PMID- 8542164
TI  - The effect of regular inhaled albuterol on exercise-induced bronchoconstriction.
AB  - Pretreatment with inhaled beta 2-agonists is often recommended for the prevention
      of exercise-induced bronchoconstriction. Regular treatment with inhaled beta 2
      agonists has been associated with worsened baseline airway caliber and increased
      airway responsiveness. In this study, we have investigated the effects of regular
      inhaled albuterol on the severity of exercise-induced bronchoconstriction using a
      double-blind, placebo-controlled, randomized, crossover design. Ten subjects
      inhaled either albuterol or placebo (2 x 100 micrograms, four times per day) for
      7 d. On the eighth and ninth days of treatment periods, subjects performed 5-min
      constant work rate cycle ergometry exercise challenges after inhaling 200
      micrograms of placebo (eighth day) or albuterol (ninth day). Forced expired
      volume in 1 s (FEV1) was measured on arrival in the laboratory as well as before
      and for 1 h after exercise. One week of regular inhaled albuterol compared with
      placebo resulted in: (1) a lower baseline FEV1 (mean difference, 230 ml) (p =
      0.02); (2) a lower minimum postexercises FEV1 without inhaled albuterol
      pretreatment (mean difference, 390 ml; range, -50 ml to 1,250 ml) (p = 0.01); (3)
      a lower minimum postexercise FEV1 with inhaled albuterol pretreatment (p < 0.01).
      The smallest degree of exercise-induced bronchoconstriction occurred after a week
      of regular placebo and pretreatment with inhaled albuterol immediately before
      exercise. Inhalation of albuterol four times daily for 1 wk worsens exercise
      induced bronchoconstriction; however, it remains extremely effective when used
      immediately before exercise for preventing bronchoconstriction.

PMID- 8542165
TI  - Rebound airway obstruction and responsiveness after cessation of terbutaline:
      effects of budesonide.
AB  - Regular monotherapy with inhaled beta 2-agonists may lead to a temporary increase
      of airway obstruction and increase of airway responsiveness after cessation of
      treatment. We investigated whether anti-inflammatory therapy may affect these
      rebound phenomena. In a double-blind, placebo-controlled study, we assessed lung
      function (FEV1) and airway responsiveness (PC20 methacholine [PC20]) during and
      after cessation of 2 wk of regular treatment with placebo and low-dose (250
      micrograms) and high-dose (1,000 micrograms) inhaled terbutaline three times
      daily. Patients with mild allergic asthma (means [+/- SD] age of 28.2 +/- 6.6 yr,
      mean FEV1% of 91.9 +/- 14.6%, and geometric mean PC20 of 0.25 mg/ml) were
      studied. One group (n = 16) was randomized to budesonide treatment, 400
      micrograms three times daily; the other group (n = 14) to placebo. PC20 and FEV1
      were measured 10, 14, 34, and 82 h after the last terbutaline or placebo
      inhalation. A different method of statistical analysis was used, in that
      measurements performed at 10, 14, and 34 h were expressed relative to 82 h values
      in each period as an area-under-the-curve (AUC) value. FEV1 did not significantly
      change during placebo and budesonide treatment. Mean PC20 and morning and evening
      peak expiratory flow were significantly higher during budesonide treatment (p <
      0.01). PC20 did not significantly change after cessation of terbutaline treatment
      in both placebo and budesonide treatment groups. AUC-FEV1 values after cessation
      of treatment with both doses of terbutaline were significantly different from the
      82 h values (p < 0.05). The decrease in FEV1 was significantly greater after the
      last terbutaline and placebo inhalation in the placebo group compared with the
      budesonide treatment group (p = 0.02). We conclude that cessation of regular
      treatment after 2 wk with both low-dose and high-dose inhaled terbutaline does
      not result in a significant rebound airway responsiveness in patients with mild
      asthma. However, the results suggest a small rebound bronchoconstriction that
      does not occur when asthmatic patients are also treated with budesonide.

PMID- 8542166
TI  - Associations of blood group-related antigens to FEV1, wheezing, and asthma.
AB  - Discordant results have been observed regarding the associations of chronic
      obstructive pulmonary diseases with secretor, Lewis, and ABO histo-blood groups,
      which are defined by glycosyltransferases. These enzymes build up oligosaccharide
      structures that play a role in the adhesion of environmental factors to
      epithelial cells. The objectives of the present study were to assess the role of
      all three systems, Lewis (Le), salivary ABH secretor (Se), and red cell blood
      group ABO, on lung function, wheezing, and asthma in a cohort of 228 coal miners
      studied cross-sectionally, considering the potential modifying effect of
      environmental factors on these associations. Asthma was significantly related to
      nonsecretor phenotype. Significantly lower lung function and higher prevalences
      of wheezing and asthma were observed in Lewis-negative or nonsecretor subjects of
      blood group O. Very low lung function values were observed in the small group of
      Lewis-negative nonsecretors who lack both Le and Se controlled fucoses (1% of
      Caucasians). Lewis-positive, salivary ABH secretors who have these two fucoses
      represent 70% of Caucasians. Among these subjects, lower lung function was
      observed in blood group A, and in a lesser extent in blood group B, i.e., with
      terminal alpha GaINAc or alpha Gal respectively, than in blood group O subjects.
      ABO, Lewis, and secretor phenotypes did not account for the potential genetic
      heterogeneity of subjects toward smoking, but alcohol consumption appeared to
      exert a protective effect on lung function in Lewis-negative subjects (10% of
      Caucasians). If confirmed in other populations, the magnitude of the effects
      observed regarding low lung function in Lewis-negative ABH nonsecretors, and the
      protective effect of Lewis negative on the deleterious effect of alcohol, may be
      of clinical importance. Further studies of the combined effects of various histo
      blood group genetic systems seem worthwhile, particularly for airflow limitation,
      wheezing, and asthma, possibly with reference to susceptibility to infectious
      agents.

PMID- 8542167
TI  - A theoretical analysis of the effect of airway smooth muscle load on airway
      narrowing.
AB  - We used published data for the elastic properties of a 2-mm outer-diameter canine
      bronchus and assumed values for the thickness of the wall components and lung
      parenchymal shear modulus to estimate the load on airway smooth muscle and its
      effect on airway narrowing. The following relationships were calculated: (1)
      luminal and smooth muscle radii of curvature and transmural pressure; (2) the
      isovolume, transmural pressures developed by the smooth muscle to narrow the
      lumen at distending pressures of 20, 10, 5, and 2 cm H2O; (3) the equilibrium
      tension developed by, and thus the load on, the airway smooth muscle as a
      function of smooth muscle length during isovolume bronchoconstriction. From these
      calculations a smooth muscle length-tension diagram was drawn allowing the
      interactions between submucosal thickening, peribronchial thickening, load, and
      smooth muscle contractility to be analyzed. The analysis indicates that: (1) the
      load on smooth muscle decreases by more than an order of magnitude between a
      distending pressure of 20 and 2 cm H2O; (2) increasing smooth muscle
      contractility has more effect at large rather than at small distending pressures;
      (3) peribronchial inflammation decreases both load and the slope of the
      relationship between peribronchial and pleural pressures. Decreases in load may
      be an important mechanism producing excessive bronchoconstriction in asthma.

PMID- 8542169
TI  - Nocturnal cortisol secretion in healthy adults before and after inhalation of
      budesonide.
AB  - We have previously demonstrated dose-dependent nocturnal cortisol suppression by
      inhaled beclomethasone and budesonide in asthmatic children. This has now been
      confirmed in a controlled study. Eighteen healthy adults inhaled either a single
      evening dose of 400 micrograms budesonide or placebo or 400 micrograms budesonide
      twice daily for 2 wk. Overnight blood samplings for cortisol and
      adrenocorticotropic hormone were taken at the beginning of the trial, at the end
      of the treatment period, and after stopping the medications. Compared with
      placebo, the nocturnal cortisol production was significantly reduced by 40% after
      a single dose of budesonide (p = 0.020) and by 37% after 2 wk of budesonide (p =
      0.045). These data indicate that there is a single-dose rather than a cumulative
      suppressive effect of inhaled corticosteroids using the specific dose and regimen
      studied in this protocol. The effect is not related to the underlying problem,
      namely asthma. The clinical relevance of these findings can only be elucidated in
      long-term follow-up studies. We believe that our findings explain the recent
      identification of abnormalities in bone turnover on inhaled corticosteroids in
      the absence of other systemic effects. The findings emphasize the need for a
      cautious step-wise approach to asthma therapy.

PMID- 8542168
TI  - Inflammatory cell populations in bronchial biopsies from aspirin-sensitive
      asthmatic subjects.
AB  - The inflammatory cell infiltrate in bronchial biopsies of 12 aspirin-sensitive
      asthmatic (ASA) subjects and eight non-aspirin-sensitive (non-ASA) control
      subjects have been compared. Biopsies were taken from a right middle or lower
      lobe segmental carina using fiberoptic bronchoscopy. The biopsies were snap
      frozen in OCT, and sections 5 microns thick were doubled immunostained using a
      rabbit polyclonal antibody to the enzyme 5-lipoxygenase (5-LO) and with a
      monoclonal antibody to neutrophils (NP57), macrophages (EMB11), and total (BMK13)
      and activated eosinophils (EG2), mast cells (AA1), and T-lymphocytes (anti-CD3).
      There was no significant difference in the total numbers of cells staining for 5
      LO between the two groups of subjects. As a percentage of total 5-LO cells, there
      were significantly more mast cells (12.9 +/- 3.8% versus 3.4 +/- 3.1%; p = 0.039)
      and total eosinophils (34.7 +/- 9.4% versus 11.1 +/- 3.8%; p = 0.044) and
      significantly fewer macrophages (23.3 +/- 6.1% versus 39.8% +/- 5.3; p = 0.041)
      in the bronchial biopsies from ASA subjects as compared with non-ASA patients.
      The numbers of neutrophils, T-lymphocytes, and activated eosinophils were similar
      for the two groups. The increased numbers of eosinophils and mast cells
      identified in the bronchial tissue from aspirin-sensitive asthmatic subjects may
      be the source of the enhanced cysteinyl leukotriene production observed in these
      subjects.

PMID- 8542170
TI  - The scope of day-case surgery.

PMID- 8542171
TI  - Adjuvant therapies for solid malignancies.

PMID- 8542172
TI  - Principles of adjuvant therapy.
AB  - The use of an additional modality to improve surgical treatment of cancer is well
      established when dealing with some cancers but controversial with others. The
      reasons for this are complex, not least because the biological mechanisms by
      which tumour growth and metastasis occur are still imperfectly understood. This
      article summarises the most important applications of adjuvant therapy, with
      particular reference to breast and colorectal cancer.

PMID- 8542173
TI  - Carcinoma of the breast.
AB  - The overview of the Early Breast Cancer Trialists Collaborative Group in 1992 has
      been a watershed for current adjuvant therapy for all age groups. This article
      describes current principles of adjuvant therapy, highlighting areas of specific
      interest. In addition, the recent developments in neoadjuvant and primary medical
      treatment are described to show how future approaches will proceed.

PMID- 8542174
TI  - Adjuvant therapy for colorectal cancer.
AB  - Despite a hugh literature, there is considerable debate as to the use of adjuvant
      treatment for large bowel cancer. This article reviews some of the evidence and
      supports the entry of patients into current national trails.

PMID- 8542175
TI  - Sex and travel.
AB  - Sexually transmitted diseases have been associated with travellers since they
      were first described. The scale of international travel has increased enormously
      in the past 50 years, enabling sexually transmitted pathogens to spread with
      unprecedented speed. This article assesses the importance of international travel
      as a risk factor for human immunodeficiency virus (HIV) infection among
      heterosexuals in the UK, and suggests possible strategies for the prevention of
      HIV infection in travellers.

PMID- 8542176
TI  - Overview of immunosuppressive therapy in organ transplantation.
AB  - Immunosuppressive drugs have transformed organ transplantation from a hazardous
      experiment in the 1950s to a routine treatment in the 1990s. This article reviews
      current immunosuppressive drugs and the principles underlying their use. Newer
      agents on the horizon are also discussed.

PMID- 8542177
TI  - Microalbuminuria: a marker of systemic disease.

PMID- 8542178
TI  - FHSAs and family health services.
AB  - Family health services and their management consume a large portion of the NHS
      budget, but the key features of the services, and how they are organised, are not
      widely known. In fact the national framework for family health services predates
      the NHS as a whole by more than 30 years.

PMID- 8542179
TI  - [Tobacco among young people].

PMID- 8542180
TI  - [Cystic fibrosis: a microbiological study over an 8-year period].
AB  - OBJECTIVE: To study the microbiology of cystic fibrosis in our hospital for the
      period from 1985 to 1992. MATERIAL AND METHODS: The number of samples analyzed
      totalled 1,034, most of which were sputum and nasopharyngeal aspirates belonging
      to 113 patients (49 women and 64 men). The average age was 10 years (range: 15
      days-33 years). RESULTS AND DISCUSSION: Only 1.7% of the samples were negative.
      Normal flora were found in 10.8% and one or more potentially pathogenic
      microorganisms were found in the remaining 87.4%. Colonies were over 10(6) UFC/ml
      in size in 77.8% of the quantified cultures. The most frequently identified
      microorganisms in the population overall were P. aeruginosa (53.9%), S. aureus
      (30.3%) and H. influenzae (22.0%). In patients less than 12 months old, however,
      the most common isolations were of S. pneumoniae and B. catarrhalis; cultures
      from patients older than 16 years old most often yielded filiform fungi, mainly
      Aspergillus spp. We found no strains of Legionella spp. and P. cepacia was found
      in only 3 cases, in which the clinical outcome was good. In addition to the 3
      most common organisms, we recorded several consecutive isolations of Proteus
      mirabilis, Xanthomonas maltophilia and Serratia marcescens in patients older than
      11 years old; this finding suggests that given the improved survival of cystic
      fibrosis patients over the coming years and the antibiotic pressure placed on
      them, there may be slight changes in the bacterial ecology typical of this
      disease. No strain of S. aureus proved resistant to methicillin, but P.
      aeruginosa was shown to be resistant to gentamycin (58.2%) among the
      aminoglycosides and also to some of the beta-lactams considered to be effective,
      as follows: 25.2% to piperacillin, 22.6% to ceftazidime and even 19.8% to
      aztreonam. There was slight resistance of ciprofloxacin (6.3%).

PMID- 8542181
TI  - [A phonogramic study of expiratory wheezing in the asthmatic patient].
AB  - The quantitative analysis of expiratory wheezing may offer a new approach for
      study respiratory function in asthmatics. METHOD: The sound spectrum during
      expiration was analyzed in 9 asthmatics with wheezing and 5 normal subjects.
      Phonographic parameters were then correlated with spirometric results for
      baseline respiration and deep breathing. RESULTS: a) Expiratory wheezing is heard
      in a band of 210 to 280 Hz during deep breathing, and b) the volume in this band
      correlates positively with mean expiratory flow (VT/TE) and negatively with the
      slope of the volume/flow curve between 50 and 25% of FVC. CONCLUSIONS: The degree
      of air flow limitation in the peripheral airways correlates with the volume of
      pulmonary sound.

PMID- 8542182
TI  - [Maximal static respiratory pressures. The importance of the study of normal
      reference values].
AB  - In order to determine the validity for our population of the theoretical
      reference values available in the literature today, we studied respiratory muscle
      force by calculating maximum expiratory pressure PEmax and maximum inspiratory
      pressure (PImax) in 100 healthy subjects in Asturias (50 women) between 17 and 80
      years-old (mean 40.4 +/- 19.3 years). We used the same methods and apparatus as
      Black and Hyatt and compared the results with theoretical values given by them as
      references corresponding to our subjects, according to age and sex. Values were
      significantly lower (p < 0.001) in our population for both parameters and for
      both men and women. In men PEmax was 69.7% and PImax was 88.5% of the theoretical
      values, in women PEmax was 60.9% and PImax was 82.9%. These figures indicate that
      the theoretical values given by Black and Hyatt are not valid for the population
      we studied and that normal reference values appropriate for each population,
      laboratory and apparatus must be obtained if valid conclusions are to be reached.

PMID- 8542183
TI  - [The clinical characteristics of pleural tuberculosis in patients with and
      without human immunodeficiency virus infection].
AB  - OBJECTIVE: To determine whether or not there are differences in the
      characteristics of pleural tuberculosis (PT) related to whether patients are or
      are not infected by human immunodeficiency virus (HIV). METHODS: We conducted a
      retrospective study of the medical histories of patients diagnosed of PT in our
      hospital between 1986 and 1993. RESULTS: We found no significant differences in
      the proportions of tuberculosis patients with or without HIV infection (8% versus
      11%) who were diagnosed of PT. Of the 119 patients diagnosed of PT, 10% were also
      HIV positive. The HIV patients had more serious forms of PT, and among them there
      was a higher incidence of pleural discharge, more isolations of Mycobacterium
      tuberculosis in sputum and pleural fluid (42% and 45% versus 13% and 15%, p <
      0.05), and more deaths before end of treatment (17% versus 1%, p < 0.05). The HIV
      patients had a lower rate of positive results in Mantoux's intradermal reaction
      test (17% versus 67%, p < 0.01), however, and fewer positive results for pleural
      biopsy (36% versus 84% positivity for granulomas, p < 0.01). CONCLUSIONS: The
      frequency of PT was similar for subjects with and without HIV infection in our
      study. In patients with both HIV and PT pleural fluid and sputum cultures are
      more useful diagnostic tools than pleural biopsy, and the former tests should
      therefore be stressed.

PMID- 8542184
TI  - [Pediatric fiber bronchoscopy. Our experience].
AB  - Fiberoptic bronchoscopy is at present an indispensable technique in pediatric
      pulmonology. Sixty-nine such procedures were performed at our center between
      April 1993 and November 1994 on children under 14 years-old. We used an Olympus
      BF-3C20 fiberoptic bronchoscope, after providing sedation with diazepam or
      midazolam, sometimes accompanied by fentanyl and atropine. No intubation was
      required in 59 cases. In 9 cases intubation was orotracheal. In one patient the
      tubes were inserted outside the trachea. The indications for bronchoscopy were
      upper airways disease (16.98%), lower airways disease (75.47%) and exploratory in
      7.54%. The endoscopic findings were upper airways disease (8.6%), bronchial
      disease (52.17%), extrinsic bronchial compression (4.34%) and normal (13.04%).
      Samples were taken in 52.17%. No important complications occurred but there were
      slight decreases in oxygen saturation.

PMID- 8542185
TI  - [The lung and trips by plane].

PMID- 8542186
TI  - [Traumatic pulmonary pseudocysts].
AB  - Two cases of traumatic pulmonary pseudocysts in young patients are presented.
      Blunt chest injuries resulting from traffic accidents were the causes in both
      cases. Air cavities were seen on chest films 12 hours and one hour, respectively,
      after trauma. In both cases, self-limited hemoptysis preceded the appearance of
      an air-fluid level on X-rays. The diagnoses of pulmonary pseudocyst were made
      after excluding other possible cause and the outcomes were satisfactory after
      treatment of symptoms and associated lesions.

PMID- 8542187
TI  - [Alveolar lipoproteinosis treated by bronchopulmonary lavage].
AB  - Alveolar lipoproteinosis is a rare disease, a review of the Spanish Medical Index
      for 1971 to June 1994 showing only 9 reported cases. The intra-alveolar deposit
      of lipoprotein-type matter produces severe hypoxemia and favors infection by
      opportunistic germs. Treatment with massive bronchial lavage (MBL) removes the
      matter from the alveolar space, improves gas exchange and decreases the risk of
      infection. We report a case of primary alveolar lipoproteinosis treated with MBL
      in which the patient developed infections by Aspergillus fumigatus before lavage
      and after starting steroid treatment. The procedure was performed without
      complications, with significant clinical and gasometric improvement. The natural
      evolution of this disease is poorly understood. Spontaneous remissions have been
      observed, and as MBL is not a risk-free procedures, its use in treatment is
      controversial. We believe that when severe hypoxemia is present, MBL should be
      used early, when the risk is slight; MBL improves gas exchange and probably
      reduces the risk of opportunistic infection.

PMID- 8542188
TI  - [Localized tracheobronchial amyloidosis. The usefulness of computed tomography].
AB  - Tracheobronchial amyloidosis is the most common form of localized
      bronchopulmonary amyloidoses, although its diagnosis is rare in daily practice.
      We describe two new cases of localized tracheobronchial amyloidosis, one in the
      form of a single node and one diffuse. We discuss in particular the contribution
      of computed axial tomography, mainly for diagnosing the diffuse form, in which a
      finding of a thickened tracheobronchial wall and intraluminal nodes should lead
      to the suspicion of this entity. The treatment of choice in most cases is
      resection with an Nd-YAG laser.

PMID- 8542189
TI  - [Functional laryngeal obstruction].
AB  - We describe 4 patients with reversible obstruction of the upper airways, a
      condition that usually presents with crises of dyspnea and respiratory sounds. No
      organic cause could be identified and the symptoms were initially confused with
      those of bronchial asthma. During episodes, the flow-volume curve suggested
      obstruction of the upper airways with poor reproducibility and repeatedly normal
      resistance values. Fiberoptic bronchoscopy allowed us to confirm the functional
      nature of the obstruction in these cases.

PMID- 8542190
TI  - [An analysis of the prevalence of respiratory symptomatology in the general
      population].

PMID- 8542191
TI  - [The value of the bronchodilator test to the study of bronchial reversibility].

PMID- 8542192
TI  - [Is the pig a good study model for lung preservation?].

PMID- 8542193
TI  - Magnetic field gradients and coherence-pathway elimination.
AB  - The amount of residual transverse magnetization after the application of a pulsed
      magnetic-field gradient (PFG) is calculated for a homogeneous volume of interest
      (VOI) with three orthogonal pairs of sides and for VOIs that deviate from this
      idealized case. Many of the results can be understood in terms of the Fourier
      transform relationship between the VOI intensity profile as a function of
      position, I(x), and the residual signal as a function of net PFG strength, S(k).
      Dephasing of transverse magnetization is more effective with imperfect slice
      selection profiles, a circular sample cross section, or decreased B1 intensity
      near the edges of a sample than in the idealized case. When two or more
      orthogonal PFGs are applied, the net amount of dephasing depends on the source of
      intensity variation (sample geometry or slice-selective radiofrequency pulse
      profiles) and the orientation of the PFGs. If a gradient is parallel to one side
      of a VOI with rectangular cross sections, dephasing is more effective if a
      second, orthogonal gradient of equal intensity is added than if the original
      intensity is doubled. In contrast, if a PFG is orthogonal to the axis of an NMR
      tube with a circular cross section, addition of a second gradient orthogonal to
      the tube axis provides only slightly greater dephasing and is less effective than
      doubling the original intensity.

PMID- 8542194
TI  - Measurement of nitric oxide with a solid-state-char EPR probe.
AB  - Recently, highly oxygen-sensitive solid-state paramagnetic probes have been
      developed from glucose chars which are capable of providing measurements of very
      low, millitorr, oxygen concentrations in biological cells and tissues. With the
      increased interest and recognition of the presence and importance of the free
      radical gas nitric oxide, NO., in biology, studies were performed aimed at
      characterizing the effect of NO. on this probe. It was observed that NO. exerts a
      similar concentration-dependent broadening as does molecular oxygen, O2. In
      anaerobic solutions, concentrations of NO. could be detected down to 10-100 nM
      levels. Measurements of NO. formation in aqueous solution were performed from a
      pharmacological NO. donor, which produced micromolar concentrations of NO.. This
      technique, however, was not sufficiently sensitive to measure physiological 1-10
      nM concentrations. Thus, the glucose-char EPR probe could be used to detect
      pharmacological levels of NO. but was not significantly affected by the low
      physiological levels which occur in normal biological tissues. These results
      indicate that, under normal physiological conditions, the linewidth alterations
      measured using the glucose-char EPR probe are solely caused by oxygen.

PMID- 8542195
TI  - Identification of 2-fluoro-2-deoxy-D-glucose metabolites by 19F(1H) hetero-RELAY.
AB  - It has been proposed that in mammalian systems the glucose analog 2-fluoro-2
      deoxy-D-glucose (FDG) is phosphorylated and subsequently converted to the
      corresponding mannose derivative via the action of phosphoglucose isomerase. As
      is generally true in metabolic studies of fluorinated molecules, the fluorine
      spectrum alone is suggestive, without providing definitive structural evidence,
      while the use of 1H NMR techniques generally suffers from a lack of adequate
      selectivity. A 1H-19F version of the hetero-RELAY experiment has been applied to
      this problem. Formation of the corresponding C-6 phosphorylated 2-FDG analog with
      hexokinase, followed by treatment of the resulting phosphorylated products with
      phosphoglucose isomerase, resulted in the observation of additional 19F
      resonances consistent with the corresponding 2-fluoro-2-deoxy-D-mannose-6
      phosphate metabolite. A more definitive product identification was obtained using
      the hetero-RELAY experiment, which provides a complete 19F-decoupled proton
      spectrum for each of the fluorinated species.

PMID- 8542196
TI  - Magnetic alignment of duplex and quadruplex DNAs.

PMID- 8542197
TI  - More than just a game: research developments and issues in competitive anxiety in
      sport.
AB  - This paper provides a critical overview of developments and issues in competitive
      anxiety research. The discussion is divided into sections dealing with general
      arousal-based approaches, general anxiety-based approaches and, finally, multi
      dimensional anxiety-based approaches. The major emphasis is on multidimensional
      anxiety-based approaches, in which a number of factors and issues surrounding the
      competitive anxiety response are addressed, including: conceptual and measurement
      developments; antecedents of competitive anxiety; temporal patterning of the
      response; and frequency of competition-related cognitive intrusions. Research
      which has examined the relationship between multidimensional anxiety and
      performance is considered in detail, including debilitative and facilitative
      competitive anxiety states and catastrophe models. A control model of
      debilitative and facilitative competitive anxiety is proposed. Finally,
      recommendations for future research are suggested.

PMID- 8542198
TI  - Learning during anaesthesia: a review.
AB  - Can learning occur during general anaesthesia? This paper reviews the studies
      which have addressed this issue and finds some evidence of implicit memory for
      intra-operative events, even with clinically adequate anaesthesia. This has
      implications both for clinical practice and for psychological theories of
      learning and awareness. However, since many of the studies have been
      opportunistic, neither the anaesthetic techniques nor the paradigms used to
      assess memory have been standardized. Methodological improvements are discussed,
      in particular the need for a reliable means of monitoring awareness during
      anaesthesia. These improvements would enable researchers to determine the
      conditions under which learning occurs and would provide information about the
      role of consciousness in learning.

PMID- 8542199
TI  - Screening cervical smears.
AB  - A plausible explanation is offered why an experienced pathologist engaged in the
      screening of cervical smears should have issued a large number of false-negative
      diagnoses. The explanation centres on the interactions which occur between
      successive judgements when a sequence of similar stimuli are inspected. Briefly,
      those interactions have the character of an assimilation of each judgement to its
      predecessor, and the resultant process is capable of 'running away'. A procedure
      is suggested, involving the provision of immediate knowledge of results for a
      small proportion of the smears inspected, which would prevent such systematic
      misdiagnoses from recurring in the future.

PMID- 8542200
TI  - Joints count: a review of old and new articular indices of joint inflammation.

PMID- 8542201
TI  - Neurological involvement in systemic sclerosis.

PMID- 8542202
TI  - The Michael Mason Prize Essay (1994). Antiphospholipid antibodies and disease.

PMID- 8542203
TI  - Increased levels of beta 2 glycoprotein-I antigen and beta 2 glycoprotein-I
      binding antibodies are associated with a history of thromboembolic complications
      in patients with SLE and primary antiphospholipid syndrome.
AB  - beta 2 Glycoprotein-I (beta 2GPI), a plasma component with in vitro anticoagulant
      properties, has been identified as a cofactor for the binding of some
      antiphospholipid antibodies (aPAs). In order to determine whether beta 2GPI
      changes were associated with the thromboembolic complications of aPAs, we
      measured beta 2GPI antigen (beta 2GPI:Ag), beta 2GPI aPA cofactor activity (beta
      2GPI:Cof) and antibodies to beta 2GPI (alpha beta 2GPI) in 44 systemic lupus
      erythematosus (SLE) patients, of whom 19 had evidence of aPAs (SLE-aPA+) and 17
      patients with primary antiphospholipid syndrome (PaPS). beta 2GPI:Ag levels were
      significantly increased in SLE-aPA+ patients and PaPS patients compared with SLE
      aPA- patients and normal healthy controls. The ratio of beta 2GPI:Cof/Ag was
      significantly reduced in SLE-aPA+ patients compared with SLE-aPA- patients,
      indicating functional modification of beta 2GPI in SLE-aPA+ patients. Eighty per
      cent of patients with anticardiolipin (aCL) IgG also had alpha beta 2GPI, and 13%
      patients with no detectable aCL IgG had alpha beta 2GPI. Increased beta 2GPI:Ag
      and alpha beta 2GPI were associated with a clinical history of thrombosis or
      recurrent fetal loss. The results of these investigations suggest that beta 2GPI
      may play a role in the pathogenic mechanism of thrombosis associated with aPAs.

PMID- 8542204
TI  - sIL-2R levels in rheumatoid arthritis: poor correlation with clinical activity is
      due in part to disease duration.
AB  - The serum levels of soluble interleukin-2 receptors (sIL-2R) were measured in an
      attempt to determine whether they correlated with 'disease activity' in 59
      patients suffering from rheumatoid arthritis. Our results indicate that serum
      levels of sIL-2R do not permit patients to be classified as having active or
      inactive disease according to standard clinical indices. A correlation between
      sIL-2R and disease duration could offer one explanation for the current
      discrepancies found in the literature.

PMID- 8542205
TI  - In vitro duodenal iron uptake and serum and mucosal iron protein levels, with
      special reference to rheumatoid arthritis.
AB  - Duodenal biopsies from control subjects, patients with iron-deficiency anaemia
      and rheumatoid arthritic patients with anaemia of chronic disorders (ACD) were
      investigated for their ability to take up 59Fe from iron ascorbate. Additionally,
      duodenal tissues were analysed for iron and immunoreactive ferritin and
      transferrin. Biopsies from iron-deficient subjects showed a 2- to 3-fold increase
      in the apparent Vmax for 59Fe uptake, compared to control values. Uptake was
      inversely related to body iron stores. ACD patients showed similar rates of 59Fe
      uptake to controls; the rates were independent of the degree of anaemia or serum
      ferritin levels. Tissue analysis showed reductions in mucosal iron and ferritin
      levels in iron-deficient patients, whilst transferrin levels were within the
      normal range. ACD patients also exhibited lower mucosal iron levels, but had iron
      protein levels within the normal range. It is suggested that factors distant from
      the intestinal mucosa influence iron absorption in ACD.

PMID- 8542206
TI  - Serial circulating adhesion molecule levels reflect disease severity in systemic
      sclerosis.
AB  - Microvascular damage occurs in systemic sclerosis (SSc) and is associated with
      increased expression of endothelial adhesion molecules, including intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E
      selectin. Elevated levels of the soluble circulating forms of these molecules
      have recently been reported in SSc. We have extended this observation by
      collecting serial serum samples from 12 patients with systemic sclerosis, at
      intervals between 4 and 12 months, through the course of their disease (mean
      period of observation 44 months). Circulating ICAM-1, VCAM-1 and E-selectin were
      measured by ELISA, and changes in these levels were compared with alterations in
      disease activity as assessed by skin sclerosis score, serum creatinine,
      erythrocyte sedimentation rate and pulmonary function tests coincident with each
      serum sample. The mean levels were ICAM-1 627 ng/ml, VCAM-1 959 ng/ml and E
      selectin 81 ng/ml. In 8/12 patients, there was a substantial change in at least
      one disease parameter during the assessment period. In seven (88%) of these
      patients, changes in circulating VCAM-1 or E-selectin were associated with
      disease severity, falling with improvement in renal function or skin score, and
      rising with deterioration in pulmonary function tests. The maximum recorded level
      of VCAM-1 (3550 ng/ml) shortly preceded an acute renal SSc crisis. In two cases
      (25%), the correlation was statistically significant (P < or = 0.01). The ICAM-1
      level did not reflect clinical changes in any patients. These results provide
      further evidence for endothelial cell dysfunction in SSc, and suggest that serial
      measurements of VCAM-1 and E-selectin may have potential value as surrogate
      markers for clinical progression or remission in this disease.

PMID- 8542207
TI  - Magnetic resonance imaging of the brain in systemic lupus erythematosus.
AB  - Magnetic resonance imaging (MRI) of the brain is a sensitive method to detect
      parenchymal tissue lesions. Its value in the diagnosis of central nervous system
      (CNS) lupus is disputed. To address this question, we have conducted an open and
      prospective study in a population of 44 SLE patients. We investigated 24 patients
      (mean age 33 +/- 13 yr) with past or active CNS lupus (group A) that included
      organic brain syndrome (12), migraine (8), focal neurological signs (7), seizures
      (2), myelopathy (1) and narcolepsy-cataplexy (1), and 20 patients (mean age 32 +/
      12 yr) without CNS lupus (group B). Health controls comprising nine females and
      one male aged 31 +/- 9 yr were also studied for comparison (group C). MRI was
      performed using sagittal T1-weighted images, axial and coronal spin density, and
      T2-weighted images. All scans were read blindly. Thirteen patients in group A and
      10 in group B had well-identified lesions on sequences with long repetition time.
      Lesions were mostly multiple, small, punctate areas of increased signal at
      periventricular or subcortical white matter of both cerebral hemispheres. The
      number and location of lesions were not significantly different in both groups.
      None of the group C patients had MRI lesions. The presence of lesions was
      significantly associated with age at study and disease duration, but not with the
      presence of CNS lupus. In summary, MRI abnormalities are detected in
      neurologically asymptomatic SLE patients. Whether this represents subclinical
      brain involvement remains unknown.

PMID- 8542208
TI  - Osteoarthritis and Paget's disease.
AB  - Paget's disease of bone adjacent to the joint margin is thought to cause
      accelerated osteoarthritis of the affected joint. By analogy with the post
      meniscectomy knee model, a constitutional tendency to develop osteoarthritis may
      modify the response to Paget's disease. Sixty-nine patients with Paget's disease
      extending to include a joint margin were identified in a rheumatological out
      patient clinic, and examined clinically and radiographically. Radiographs were
      scored according to the method of Kellgren and Lawrence. Paget's disease was
      found adjacent to 100 joints: 86 hips, 13 knees and one wrist. Osteoarthritis was
      more severe in ipsilateral, compared to contralateral, joints (Mann-Whitney, P =
      0.04). A significant difference in the severity grading of index joints was found
      between groups based on the presence of osteoarthritis elsewhere (Mann-Whitney, P
      = 0.01). In conclusion, accelerated osteoarthritis was found in joints affected
      by Paget's disease, but this association may be an overestimate because of
      selection bias. In addition, the severity of osteoarthritis in affected joints
      was related to the presence of osteoarthritis elsewhere in the patient. Further
      studies are required to determine the magnitude of the effect of Paget's disease
      on the adjacent joint.

PMID- 8542209
TI  - Effectiveness of minimally supervised home aerobic training in patients with
      systemic rheumatic disease.
AB  - The effectiveness of an exercise prescription and unsupervised home exercise
      programme was tested on 37 subjects with rheumatoid arthritis and 34 with
      systemic lupus erythematosus. Subjects were randomly assigned to control or
      stationary bicycling at home, using loaned bicycles. Exercise subjects (with
      bicycles) did better than controls, but not significantly, on all outcomed
      measures (exercise tolerance test, fatigue, depression and helplessness) at 3
      months. Bicycles were reclaimed at 3 months and all subjects in both groups given
      instructions for home exercise. Exercise in the second 3 months was predicted
      primarily by baseline exercise habits and fatigue. It is concluded that although
      safe, unsupervised home exercise programmes may benefit few patients. Future
      research should address methods of stimulating and maintaining unsupervised
      exercise programmes in patients with systemic rheumatic disease.

PMID- 8542210
TI  - Manipulative physiotherapy for spinal problems in primary care: outcomes of care.
AB  - Outcome measures for physiotherapy in a primary health care setting should be
      evaluated before physiotherapy becomes widely available in general practice. The
      aim of this study was to assess changes in outcome measures in patients with
      spinal problems treated with bed rest, advice and analgesia ('traditional'
      treatment) and with manual/manipulative physiotherapy ('active' treatment). A
      retrospective analysis was carried out of computerized records of patients
      treated in primary care with manual and manipulative physiotherapy for spinal
      problems and a group with a similar age/sex/diagnosis profile who were given
      traditional treatment. Outcome measures in the 12 months following the initial
      diagnosis were: referrals, recurrences, casualty attendances, X-rays and number
      of prescribed analgesic and non-steroidal anti-inflammatory agents (NSAIDs). In
      the active group, there were 231 lumbar and 154 cervical patients, and 82 and 75,
      respectively, in the traditional group. There was a significant decrease in the
      recurrence rate [odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.37-0.84]
      and in the numbers attending casualty (OR = 0.19, 95% CI 0.04-0.76) for 'active'
      compared with 'traditional' patients. For patients with cervical problems, there
      was a significant decrease in the active group of NSAIDs prescribed (P < 0.05).
      Certain outcomes of spinal problems are improved by the provision of manipulative
      physiotherapy in general practice.

PMID- 8542211
TI  - Inflammatory back pain in primary care.
AB  - Three-hundred-and-thirteen back pain sufferers completed a screening
      questionnaire for inflammatory back pain. This was positive in 46 (15%), who were
      invited for a further examination. Only two of these patients had definite
      ankylosing spondylitis. Eighteen of them (39%) had other features associated with
      spondyloarthropathy. It is suggested that up to 5% of back pain sufferers may
      have a mild form of ankylosing spondylitis that may never progress to definite
      ankylosis, but for whom treatment as if they had ankylosing spondylitis may be of
      benefit.

PMID- 8542212
TI  - In the rheumatoid patient: surgery to the cervical spine.

PMID- 8542213
TI  - Proteinaceous lymphadenopathy in a patient with known rheumatoid arthritis--case
      report and review of the literature.
AB  - We describe a case of proteinaceous lymphadenopathy (also called lymph node
      hyalinosis) in a 30-yr-old woman with known rheumatoid arthritis (RA).
      Amyloidosis was excluded by negative staining with congo red viewed with and
      without polarized light. Proteinaceous lymphadenopathy should be included in the
      differential diagnosis of patients with lymphadenopathy and long-standing RA. The
      histopathologist should be familiar with the morphological appearances of this
      condition, which can be confused with amyloidosis. It appears that there is a
      good clinical response in RA-associated proteinaceous lymphadenopathy following
      successful treatment of arthritis.

PMID- 8542214
TI  - Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis
      associated with anti-thyroid drug treatment.
AB  - Two cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis
      following treatment with propylthiouracil and carbimazole are described. Both
      patients had crescentic glomerulonephritis proven by renal biopsy and responded
      to immunosuppressive therapy and withdrawal of the anti-thyroid drugs. Though
      systemic vasculitis associated with propylthiouracil is reported, this is the
      first report to our knowledge of renal biopsy-proven vasculitis associated with
      either of these drugs.

PMID- 8542215
TI  - Acquired Brown's syndrome in systemic lupus erythematosus.
AB  - A 33-yr-old woman with systemic lupus erythematosus (SLE) and concomitant
      development of Brown's syndrome is described. This rare complication of SLE is
      discussed.

PMID- 8542216
TI  - Lymphocyte reactivity to Clostridium perfringens antigens and toxoid in patients
      with arthritis.

PMID- 8542217
TI  - Psoriatic arthropathy after BCG immunotherapy for bladder carcinoma.

PMID- 8542218
TI  - Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic
      disease.

PMID- 8542219
TI  - Computerized transverse axial scanning (tomography): Part I. Description of
      system. 1973.

PMID- 8542220
TI  - Invited review: Rontgen and the discovery of X-rays.
AB  - This review celebrates the events of 100 years ago to the month of publication of
      this November 1995 issue of the British Journal of Radiology, when X-rays were
      discovered by Rontgen (8 November 1895) and he was working in his laboratory
      leading up to his 28 December 1895 communication "On a new kind of ray".
      Biographical details of Rontgen are given, together with his work in Wurzburg
      before the discovery and popular and scientific opinion in the immediate months
      after the world first learned of the existence of X-rays. Some of Rontgen's
      apparatus is illustrated, accompanied by typical advertisements of 1896-1897.
      Where appropriate I have included information related to the UK, concerning, for
      example, Sir Arthur Schuster and Lord Kelvin; there is also a mention of the
      Rontgen Society, the forerunner of today's British Institute of Radiology.

PMID- 8542221
TI  - The appearance of "early" chest radiographs and the response to surfactant
      replacement therapy.
AB  - We have assessed whether the appearance of the chest radiograph performed within
      the first 2 h of birth was predictive of the response to exogenous surfactant
      replacement therapy (SRT), as indicated by changes in sensitive indices of
      disease severity, that is lung volume (functional residual capacity (FRC)) and
      oxygenation (a/A ratio). 18 premature infants who received two doses of a
      synthetic surfactant (Exosurf) were studied. The appearances of chest radiographs
      taken prior to the first and immediately after the second dose of SRT were scored
      for lung volume, degree of inflation, presence of opacification, interstitial
      shadows and air bronchograms. At similar times, FRC was measured and the a/A
      ratio calculated. Although following SRT, the chest radiograph score decreased (p
      < 0.01) and the FRC (p < 0.01) and a/A ratio (ns) improved, there was no
      significant relationship between the change in chest radiograph score and either
      the change in FRC or a/A ratio. In addition, only the post-SRT chest radiograph
      appearance correlated significantly with the respective FRC, a/A ratio and
      outcome (death or oxygen dependency beyond 28 days). Although the appearance of
      an early chest radiograph is frequently used as an indicator of the need for SRT,
      these results demonstrate that, unlike the post-SRT radiograph, it is a poor
      predictor of the response to SRT and outcome.

PMID- 8542222
TI  - A comparison of the methods of distraction for stress examination of the
      acromioclavicular joint.
AB  - Acromioclavicular joint disruption is frequently evaluated with a radiographic
      examination of the joint under stress (weight bearing). Certain authors recommend
      suspending the weights from the arm, rather than being hand-held, to allow for
      total muscle relaxation. This study examines the relationship between the
      coracoclavicular distance measured and the method of distraction. 30 normal
      subjects participated in the study which used ultrasound (5 MHz linear array) to
      measure the coracoclavicular distance under four conditions (levels of traction):
      non-stressed, muscles relaxed; non-stressed, muscles tensed; stressed with 7.5 kg
      weight hand held; stressed with 7.5 kg weight suspended from the wrist. The data
      were subjected to a multifactor ANOVA. The level of traction was statistically
      significant (p < 0.001). The data were then subjected to a Bonferroni multiple
      comparisons procedure. This showed a difference between the non-stressed and
      stressed conditions, but there was no difference between the two methods of
      applying stress to the joint. It was concluded that, in normal subjects, the
      method of performing the weight bearing examination does not have a significant
      effect on the magnitude of the coracoclavicular distance.

PMID- 8542223
TI  - Quantitative perfusion parameters of focal nodular hyperplasia and normal liver
      parenchyma as determined by electron beam tomography.
AB  - Eight patients with known focal nodular hyperplasia (FNH) were studied by
      electron beam tomography (EBT) in a multisection flow mode at defined time
      intervals after intravenous contrast agent injection. Various regions of interest
      (ROIs) were defined in the areas of FNH, normal liver parenchyma, aorta and
      portal vein. In each ROI density changes were measured and plotted against time.
      In those time-density curves (TDCs) the slope, the time of maximal enhancement
      and the absolute density value of peak enhancement were determined. Arterial
      tissue perfusion was calculated for normal liver parenchyma and FNH. In all eight
      patients significant differences in peak density (123.88 +/- 18.92 HU vs 102.5 +/
      15.49 HU, p = 0.012), in the rate of arterial contrast enhancement (252.63 +/-
      28.05 HU min-1 vs 38.88 +/- 4.19 HU min-1, p = 0.012) and in the arterial tissue
      perfusion (1.36 +/- 0.19 ml min-1 cm-3 vs 0.21 +/- 0.03 ml min-1 cm-3, p = 0.012)
      between FNH and normal liver parenchyma were found. Perfusion values of normal
      liver parenchyma correspond to those determined by inert gas clearance. Further
      studies will determine the practicability of this quantitative method in the
      evaluation of global and other focal liver diseases.

PMID- 8542224
TI  - Follow-up of spongiosa plugs with contrast enhanced magnetic resonance imaging.
AB  - The aim of this study was to evaluate the extent and duration of the
      revascularization process in spongiosa plugs when a fibrin sealant was used. 20
      patients with tumour-like lesions, benign tumours and tumours with a potential
      for malignant transformation were studied. After intralesional tumour removal,
      the defect was filled with homologous spongiosa either combined with or without a
      fibrin sealant, according to a prospective randomization. Magnetic resonance
      imaging (MRI) follow-up examinations were performed within 1 week, and 1.5, 3,
      4.5, 6, 8, 12, 24 and 36 months after surgery. Those patients without a fibrin
      sealant showed an increased revascularization zone up to the sixth week. Patients
      treated with fibrin, however, showed increased revascularization up to 3 months.
      In the 25% percentile the extent as well as the rate of revascularization is
      higher in those with a fibrin sealant. It is of clinical relevance that no
      revascularization should be expected at 3 months after surgery, which is easily
      demonstrated by MR follow-up.

PMID- 8542225
TI  - Spin lock magnetic resonance imaging in the differentiation of hepatic
      haemangiomas and metastases.
AB  - Spin lock (SL) imaging technique, generating T1 rho-weighted images, was applied
      to the differentiation of hepatic haemangiomas from metastatic focal liver
      lesions. 17 haemangiomas and 16 metastases in 32 patients were imaged at the
      field-strength of 0.1 T using a multiple slice SL technique and a conventional
      gradient-echo (GRE) sequence with identical timing parametres. Spin lock effects
      of the hepatic lesions and different abdominal tissues were calculated. Images
      with adequate coverage of the liver and of good quality with few motion induced
      artefacts were acquired. A definite, statistically significant, difference was
      found between the SL-effects of hepatic haemangiomas and a liver metastases.
      Haemangiomas showed an SL effect of 46.6 +/- 3.4% and metastases of 56.2 +/- 5.8%
      (mean +/- SD, p < 0.0001). The multiple slice SL technique showed potential in
      distinguishing haemangiomas from metastatic liver lesions and should be
      considered as an alternative to the conventional T2 and magnetization transfer
      (MT) based methods.

PMID- 8542226
TI  - Isotope bone scans in patients with painful knee replacements: do they alter
      management?
AB  - A retrospective review of the scintigraphic appearances, clinical findings and
      outcome in 12 patients presenting with painful knee replacements was made. Three
      patients required revision surgery; symptoms in the remaining nine patients
      settled without operative management. Three examinations failed to identify
      prostheses proven to be infected by aspiration and four were falsely positive for
      infection without supportive clinical evidence. Four examinations demonstrated
      loosening and in one patient the bone scan was normal but the prostheses was
      loose at revision surgery. There were no specific features to predict which
      prostheses required surgical revision and the ability to diagnose or exclude
      infection was limited. It is concluded that the results of three phase 99Tcm bone
      scans in symptomatic knee prostheses are of little assistance in guiding clinical
      management and that a period of conservative management should be considered
      prior to operative intervention.

PMID- 8542227
TI  - Identification of a hypoperfused segment in bull's-eye myocardial perfusion
      images using a feed forward neural network.
AB  - Artificial neural networks are computer systems which can be trained to recognize
      similarities in patterns and which learn by example; one of the more
      straightforward types being the feed forward neural network (FFNN). We previously
      reported the use of FFNNs for classification of hypoperfusion patterns in bull's
      eye representation of 201Tl single photon emission tomography myocardial
      perfusion studies and showed that, when such an image was divided into 24
      segments, FFNNs could detect perfusion defects without direct comparison to a
      normal data base. This has been extended in this investigation to assess the
      ability of an FFNN, trained on data in which only a single segment was
      hypoperfused, to detect this abnormal segment when the hypoperfusion pattern of
      the other segments in the image varied. The results indicated that the network
      could reliably determine whether a segment was normally or under perfused, with
      accuracies of 99% and 100%, respectively, if all other segments were normally
      perfused. It could also reliably detect a normally perfused segment, even if
      other segments were hypoperfused, with accuracies of 95% and 98%. The network was
      less reliable, however, in detecting a hypoperfused segment when other segments
      were also hypoperfused, showing accuracies of only 74% and 88%.

PMID- 8542228
TI  - Broadband ultrasonic attenuation: are current measurement techniques inherently
      inaccurate?
AB  - Measurements of broadband ultrasonic attenuation (BUA) are currently made using
      large aperture, piezoelectric transducers. The use of such a receiver is known to
      lead to the possibility of an overestimate of ultrasonic attenuation due to phase
      cancellation and it is shown theoretically that this same effect can also lead to
      an overestimate of BUA. Using a new scanning approach, BUA was measured using two
      methods, one sensitive to the phase of the acoustic wave, the other not. The
      phase sensitive BUA measurements were found to be of significantly higher value
      (p < 0.0001) than the phase insensitive measurements with a mean difference of
      31.2 dB MHz-1. These findings are compatible with the hypothesis that BUA
      measurement systems with large aperture, piezo-electric receivers are inherently
      inaccurate.

PMID- 8542229
TI  - Patient dose values in interventional radiology.
AB  - Large exposures incurred in interventional radiology procedures make it advisable
      to establish reference dose values. These dose values should be quoted in
      quantities representative of the radiological risk to the patient. In Spain,
      measurement methods were developed to comply with the European Directive on
      Patient Protection. Dose-area product and, when feasible, surface dose using
      thermoluminescent dosimetry chips were measured. Both approaches are discussed,
      as well as their potential use in patient protection programmes. Initial results
      are presented for a sample of 680 patients in 10 hospital centres in Spain. Mean,
      median and range are reported for some specific procedures. Mean values of 8750,
      6651, 6663, 9292 and 6816 cGy cm2 are reported for percutaneous transluminal
      coronary angioplasty, coronary angiography, low extremity, renal and cerebral
      arteriographies, respectively.

PMID- 8542230
TI  - Optimization of radiographic technique for chest radiography.
AB  - Over 1500 patients undergoing chest radiography in the West Midlands have been
      monitored for entrance surface doses using lithium borate thermoluminescent
      dosemeters. In total 63 X-ray tubes were monitored from 30 hospital departments.
      The mean patient entrance surface dose is 0.15 mGy, and the 75th percentile
      entrance surface dose is 0.18 mGy. A reference level of 0.18 mGy has been
      recommended for PA chest radiography in the West Midlands. Image quality has been
      assessed on patient radiographs. Departmental radiologists were responsible for
      assessing radiographs taken within their hospital. Independent analysis was
      performed by a control radiologist. Film-screen processor sensitivity has been
      assessed on 48 film-screen processor combinations. Significant differences were
      observed between the nominally quoted sensitivities and the measured
      sensitivities. Only 26% of systems produced measured sensitivities within 10% of
      the nominal values. A four variable regression model, explaining 78% of the
      variance, provided the best description for the variation in patient dose. These
      variables were actual sensitivity, applied potential, generator waveform and
      radiographic quality. Four recommendations have been made to lower patient doses;
      these are: (1) an increase in applied potential to a minimum of 90 kVp; (2) a
      film-screen sensitivity of 400; (3) optimization of processor performance and (4)
      regular radiological audits to reduce repeat rates to a level of 5%. If all of
      these recommendations are followed, an estimated overall entrance surface dose
      saving of 53% would result. Changing the applied potential alone will see the
      variation in the mean entrance surface dose from non-gridded systems reduce from
      a factor of 4 to a factor of 2.

PMID- 8542231
TI  - Calculation of the biological effect of fractionated radiotherapy: the importance
      of radiation-induced apoptosis.
AB  - The total effect (TE) has been calculated for two different fractionation
      formalisms: the consecutive and repetitive fractionation mechanism, using a
      modified linear quadratic (LQ) model which includes the effect of apoptosis. For
      a given total dose, an increase in TE is seen when increasing the dose per
      fraction as well as the apoptotic fraction (Fa). Also, the TE increases with
      increasing alpha/beta ratio (of the modified LQ model). The ratio of TE for
      tumour tissue and TE for late reacting tissue is calculated assuming the absence
      of apoptosis in late reacting tissue and a common value of alpha/beta (of the
      modified LQ model). The biological effect ratio (BR) is higher for a large Fa and
      low doses per fraction, than for large doses per fraction and a small Fa.
      Assuming a consecutive fractionation mechanism, the TE formalism is unable to
      predict a log cell kill of more than 3 for beta values of 0.010-0.028. It is less
      dependent on dose per fraction and Fa than the repetitive fractionation
      mechanism. The biological effect ratio is only slightly higher than 1, and is
      less influenced by Fa, dose per fraction and alpha/beta ratio. A repetitive
      fractionation mechanism is also consistent with the preliminary results of
      published fractionation experiments. The calculations indicate that designing
      fractionation regimes for optimization of biological effect is a process where
      the role of apoptotic cell inactivation must be maximized, and where the
      influence of mitotic cell inactivation may be of less importance.

PMID- 8542232
TI  - Dose rates and energy spectra in the maze of a linear accelerator treatment room.
AB  - When designing an entrance maze for a linear accelerator facility, it is useful
      to be able to estimate both the dose rate at the entrance and, in case further
      shielding is necessary, the energy spectrum of the scattered photons reaching the
      maze entrance. This study examines the applicability of the commonly used
      empirical formula contained in the National Council on Radiation Protection and
      Measurements (NCRP) Report No. 51 for estimating the dose rates at the maze
      entrance in a typical treatment room, and proposes an improvement allowing for
      the fact that the initial scattering event occurs most often in the patient at
      the isocentre. The X-ray energy spectrum at the maze entrance is also measured
      and shown to have a lower average energy than is assumed in NCRP Report No. 51.

PMID- 8542233
TI  - Technical note: thyratron performance--dependence on mounting in a medical linear
      accelerator.
AB  - A thyratron is an important component of a medical linear accelerator. The
      working life of a thyratron has been found to be dependent on its physical
      orientation in the accelerator. This observation is a result of maintaining
      accelerators for over 15 years.

PMID- 8542234
TI  - Technical note: measurement of collapse cavitation in ultrasound fields.
AB  - This note describes a method for the measurement of hydroxyl free radical
      concentration due to collapse acoustic cavitation in medical ultrasound fields
      using aqueous terephthalic acid (TA) solution. An enclosed cylindrical chamber
      with acoustically transparent membranes at either end was used. Control of
      cavitation activity was achieved by seeding the solution with polystyrene
      microspheres to provide cavitation centres. Insonation experiments using unseeded
      TA previously exposed to air gave very variable results, sometimes detecting
      cavitation activity and at other times detecting nothing, under the same exposure
      conditions. Introduction of polystyrene microsphere seeds into the TA enabled it
      to detect reproducibly levels of cavitation activity at least one order of
      magnitude higher than in unseeded solutions. An experiment using the seeded TA in
      a standing wave ultrasound field, set up using a brass reflecting plate,
      demonstrated that the presence of a standing wave inhibited the measured
      cavitation yield.

PMID- 8542235
TI  - Technical note: oroantral fistula: improved imaging with a dental computed
      tomography software program.
AB  - Oroantral fistula (OAF) is an uncommon complication in oral surgery. About 5% of
      all extractions of maxillary premolars or molars may result in communication to
      the antrum. Small fistulae, 1-5 mm in diameter may close spontaneously, but
      larger fistulae usually require surgical closure. Pre-operative determination of
      the size of the fistula is often unreliable leading to difficulties in planning
      subsequent clinical management. We report a method for the precise determination
      of the size of the OAF using a dental computed tomography (CT) software program.

PMID- 8542236
TI  - Case report: renal scintigraphy in the diagnosis of urinary extravasation.
AB  - Renal scintigraphy is a sensitive method for disclosing urinary extravasation.
      Its role following a road traffic accident is clearly presented in this case
      report. It is concluded that such a study can fill an important gap between the
      clinical and intravenous urography assessment and the more invasive studies in
      trauma victims.

PMID- 8542237
TI  - Case report: neonatal platyspondylic dwarfism--a new form.
AB  - A new type of neonatal bone dysplasia is reported. Unusual radiographic
      abnormalities (platyspondyly with unique shape of the vertebral bodies,
      shortening of the long tubular bones without signs of rickets or metaphyseal
      dysplasia, marked shortening of well-ossified short tubular bones,
      schneckenbecken-like pelvis with tri-radiate acetabulum, pseudoepiphysis of the
      right ulna, unusual shape of calcaneus and periarticular calcifications) allow
      designation of this disorder as a new form of neonatal dwarfism.

PMID- 8542238
TI  - Case report: primary non-Hodgkin's lymphoma of the bladder.
AB  - Primary lymphoma of the bladder is uncommon. Less than 75 cases have been
      reported so far in the literature. Two further cases are reported here and
      relevant literature is reviewed.

PMID- 8542239
TI  - Case of the month: atypical chest pain!

PMID- 8542240
TI  - Dosimetric considerations in 131I-MIBG therapy for neuroblastoma in children.

PMID- 8542241
TI  - The role of alpha interferon in the biomodulation of disease: preface.

PMID- 8542242
TI  - Alpha interferon as an immunomodulator in the treatment of patients with tumors.

PMID- 8542243
TI  - Interferons and other cytokines in head and neck cancer.
AB  - The use of cytokines in head and neck cancer is increasingly under investigation.
      Clinical trials have tested the interferons, interleukin-2 and other cytokines as
      single agents and in various combinations. The addition of interferon to the
      cisplatin and 5-fluorouracil (5-FU) regimens (with and without leucovorin) has
      been explored. A randomized international trial comparing cisplatin and 5-FU with
      cisplatin, 5-FU and interferon-alpha 2b is in progress.

PMID- 8542244
TI  - Modulation of 5-fluorouracil by interferon: a review of potential cellular
      targets.

PMID- 8542245
TI  - Experience with interferon alpha 2b combined with dacarbazine in the treatment of
      metastatic malignant melanoma.
AB  - A prospectively randomized trial was undertaken to compare dacarbazine (DTIC)
      alone with DTIC plus interferon in patients with metastatic malignant melanoma.
      Of the 73 patients who entered on the study, 36 were randomized to receive DTIC
      alone and 37 were randomized to receive the combination DTIC plus interferon. The
      two sections were well balanced. There was more toxicity on the combination
      section, but no life threatening toxicity. The overall response rate for patients
      on DTIC was 20% (two complete and five partial responses) (95% CI 7-39%) and for
      patients on DTIC plus interferon was 50% (13 complete and four partial responses)
      (95% CI 26-72%) (p = 0.007). The median time to treatment failure, was
      significantly more in favour of the combination treatment (9 versus 2.5 months; p
      < 0.01, Mantel-Cox). The median survival of 16.7 versus 8 months was in favor of
      the combination treatment (p < 0.01). The reasons for the improved results with
      the combination treatment are discussed. The Eastern Cooperative Oncology Group
      is currently, based on the results of this study, investigating the role of
      interferon combinations in metastatic malignant melanoma.

PMID- 8542246
TI  - Interferon and chronic myelogenous leukaemia.
AB  - Interferon (IFN) is widely employed in the therapy of chronic myelogenous
      leukaemia because of its ability to exert the antiproliferative activity on
      leukaemic haematopoietic progenitors and for the expression for IFN-alpha
      receptors by peripheral blood leukaemic cell surfaces. There is no difference
      between recombinant IFN alpha 2b and alpha 2a regarding their efficacy in the
      treatment of Ph-positive CML patients. Either no randomized studies or the
      randomized ones show a superior effectiveness of IFN given as single agent in the
      induction treatment to that one of chemotherapy regarding the complete cytogenic
      response percentage. The ability of IFN-gamma to induce the expression of
      adhesion molecules such LFA 1 and ICAM 1 on peripheral blood leukaemic cell
      surfaces may suggest its use in the induction therapy of CML patients. Other
      than, a superior effectiveness of combined therapy including interferon and
      chemotherapy agents compared to chemotherapy alone has also been found. Finally
      no large series of trials to study the IFN efficacy both as second line treatment
      and maintenance therapy have been carried out.

PMID- 8542247
TI  - Pharmacokinetic interaction of 5-fluorouracil and interferon alpha-2b with or
      without folinic acid.
AB  - The purpose of this study was to evaluate a potential pharmacokinetic (PK)
      interaction between fluorouracil (5-FU) and the biomodulating agent interferon
      alpha (IFN-alpha) in patients with metastatic colorectal carcinoma. 5-FU was
      applied as an intravenous bolus injection of 750 mg m-2 weekly and IFN-alpha 2b
      (IFN) 5 MU was injected 3 times weekly (TIW) subcutaneously. In the first study,
      13 patients were treated by this schedule, 5-FU plasma levels were determined by
      HPLC on day (d) one as baseline before starting IFN; the analysis was repeated at
      the second or third cycle of 5-FU administration 1 hour after the last IFN
      injection respectively. In the second study, 10 patients additionally received
      folinic acid (FA) 200 mg m-2 as a short time infusion immediately before 5-FU,
      and a third analysis of FU kinetics was performed in order to compare the
      influence of a double modulation of IFN and FA to IFN alone. Combination of 5-FU
      and IFN resulted in a significant increase of the AUC of 5-FU (80%) and the
      fictive initial concentration (C0, 65%) obviously caused by a reduction of 5-FU
      clearance by 50%. However, when FA was added to this schedule, no significant
      changes of FU kinetics compared to 5-FU alone could be documented. Finally, in
      two pilot patients 5-FU 750 mg was given as a continuous infusion (CI) over 5
      days and IFN 5 x 10(6) u was added daily from d2 to d5.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8542248
TI  - Interferon-induced acute renal failure: a case report and literature review.

PMID- 8542249
TI  - Alpha interferon: new associations in haematology/oncology. The Montpellier
      experience.

PMID- 8542250
TI  - Interferon and multiple myeloma.
AB  - In vivo and in vitro studies are used to investigate interferon's use treating
      human multiple myeloma. In vitro studies demonstrate that the production of
      monoclonal immunoglobulin by myeloma plasma cells is reduced by alpha interferon;
      furthermore, interferon alpha seems to inhibit myeloma cell lines development. In
      vivo studies using interferon in the treatment of multiple myeloma experimentally
      reproduced in mice show low percentages of mortality among mice treated with high
      doses of interferon as opposed to high mortality among those treated with low
      doses. Clinical trials to evaluate the interferon efficacy in the treatment of
      human multiple myeloma demonstrate that the therapy of previously untreated
      patients using interferon is not useful because the response rate is lower than
      that of chemotherapy. There is no homogeneity of results of combined chemotherapy
      plus interferon as induction treatment of previously untreated patients.
      Homogeneous results are also not obtained using interferon alone or in
      combination with chemotherapy as a second induction treatment of relapsed
      patients. However, interferon seems to be effective as maintenance therapy of a
      response obtained with previous chemotherapy.

PMID- 8542251
TI  - Interaction of alpha-interferon with chemotherapeutic agents: effects on
      cytotoxic drug metabolism and multiple drug resistance.

PMID- 8542252
TI  - Evolution of regional identity in the vertebrate nervous system.
AB  - When and how did the mechanisms controlling regional identity in the vertebrate
      neural tube arise during evolution? The anatomy and embryology of the major
      deuterostome phyla (echinoderms, hemichordates, chordates) suggest that a true
      neural tube with dorsoventral and mediolateral regionalization arose with the
      chordates. We suggest that this was intimately associated with the origin of the
      notochord; this leads us to propose a modification of Garstang's century-old
      scenario for origins of the chordate neural tube. Differences along the
      rostrocaudal axis are seen in all chordates, but became particularly pronounced
      with the origin of a brain in craniates. Recent molecular data are starting to
      give insights into these evolutionary transitions. Here we review how Hox gene
      expression patterns are giving clues to brain origins and we examine the role of
      molecular phylogenetics in these analyses. We also ask whether the molecular
      evolution of genes such as noggin, Brachyury, Sonic hedgehog, Wnt, and En may
      have played direct or permissive roles in the origins of the neural plate,
      notochord, floor plate, and brain.

PMID- 8542253
TI  - Genetic control of segmentation in the vertebrate hindbrain.
AB  - Studies of cell commitment and gene expression suggest that the subdivision of
      the hindbrain into segments and the specification of their anteroposterior
      identity emerges from a prepattern in the early neural plate. This prepattern
      imposes a regional specification, but not a commitment of individual cells to
      specific segments, and may involve the spatial expression of the Krox-20 and Hox
      genes. The generation of null mutants has shown that the Krox-20 gene is required
      for the formation of definitive r3 and r5, and the Hoxa-1 gene is required for r4
      and r5 development. A mouse mutant, kreisler, has disrupted hindbrain
      segmentation, with r5 and r6 failing to form. Studies of gene expression in these
      mutants suggest that the kreisler gene has an early role, whereas the Krox-20 and
      Hoxa-1 genes have later roles in the formation of definitive segments. I propose
      that a community effect of cell-cell signaling may underlie the commitment of
      cells to specific segments and discuss the implications of this for the phenotype
      of segmentation mutants. The receptor tyrosine kinases encoded by the Sek-1, Sek
      2, Sek-3, and Sek-4 genes are segmentally expressed and could mediate cell-cell
      interactions that regulate cell commitment and hindbrain segmentation.

PMID- 8542254
TI  - Neural induction and neurogenesis in amphibian embryos.
AB  - Neural induction has long been known as the process by which the ectoderm of
      vertebrate embryos initiates neural development. During this inductive
      interaction, a region of the embryo called the organizer is a source of inducing
      signals that directs ectoderm away from an epidermal into a neural fate, thereby
      forming the neural plate and tube. In this review, we will discuss recent
      progress in characterizing two molecules in Xenopus embryos, noggin and
      follistatin, which appear to have many of the properties expected of neural
      inducers produced by the organizer. In addition, we will discuss progress that
      has been made in characterizing Xenopus homologs of the neurogenic and proneural
      genes that control the decision between a neural and epidermal fate in the
      Drosophila embryos. A model is presented in which these genes act downstream of
      neural induction in vertebrates to control the generation of neural precursor
      cells during neurogenesis.

PMID- 8542255
TI  - Regionalization of the forebrain from neural plate to neural tube.
AB  - The vertebrate central nervous system is subdivided into distinct regions along
      the anteroposterior axis. It has been suggested that segmentation may play an
      important role in the regionalization and patterning of the neural tube, in
      particular in the development of the hindbrain. Recent evidence suggests that
      this may be true also in the forebrain. Several criteria that have been used to
      define segments and that have led to different views on how the anterior neural
      tube is subdivided will be discussed. However, regionalization of the neural
      ectoderm is a gradual and continuous process that starts as early as the
      induction of neural ectoderm. At the neural plate stage, distinct domains of gene
      expression have been established, indicating that a certain amount of
      regionalization has already taken place. Segmentation, as defined by lineage
      restriction between proposed segments or by the formation of morphological
      segment boundaries, is not thought to have occurred at the neural plate. When
      viewed in this context, segmentation may be considered a relatively late event in
      the ontogenesis of the nervous system. The early pattern of gene expression, the
      organization of the neural plate, and the underlying signals and tissue
      interactions may provide us with a better understanding of how the forebrain is
      regionalized.

PMID- 8542256
TI  - Patterning of the vertebrate neural crest.
AB  - The mechanisms underlying neural crest cell migration are beginning to be
      understood thanks to the ability to combine a number of techniques in
      experimental embryology, cell and molecular biology. In the trunk, cell-cell
      interactions may predominate, so that the mesodermal somites control the
      rostrocaudal patterning of neural crest cells and the notochord prevents neural
      crest cells from crossing the midline. In the hindbrain, the segmental migration
      of neural crest cells may be influenced both by information inherent to the
      rhombomeres coupled with environmental signals from neighboring tissues, such as
      the otic vesicle. There is clearly an intimate relationship between migrating
      neural crest cells, the neural tube from which they emerge, and tissues through
      which they move. All of these elements are integral in the control of neural
      crest migration.

PMID- 8542257
TI  - Mechanisms and molecules controlling the development of retinal maps.
AB  - All mature vertebrates exhibit precise topographic mapping from the retina to the
      tectum, or its mammalian homologue, the superior colliculus (SC). In frogs and
      fish the development of this projection is precise from the outset; in avians
      retinal axon targeting is more diffuse but respects a coarse topographic
      matching; and in rodents early projections show no topographic specificity.
      Topography in avians and rodents emerges from a process of branch extension,
      arborization, and elimination of aberrant axonal projections. Despite these
      differences, the basic mechanisms controlling the development of this retinotopy
      are conserved. It has been hypothesized that molecules distributed in a position
      dependent manner in the retina and the tectum or SC control the development of
      these maps. A number of candidate molecules have been identified on the basis of
      their distribution, or their ability to influence axonal growth in vitro. In
      addition, transcription factors and signaling molecules are expressed in a
      position-dependent manner and may regulate the expression of molecules involved
      in retinotopic map formation.

PMID- 8542258
TI  - Portal hypertension revisited.

PMID- 8542259
TI  - Stress echocardiography.
AB  - Stress echocardiography has now emerged from the days of research and clinical
      evaluation to take its place alongside other non-invasive imaging methods in
      coronary artery disease. It is safe, versatile, and clinically accurate. It has
      been validated against radionuclide perfusion imaging; the cost and convenience
      advantages for echocardiography must be balanced against the greater automaticity
      and probable sensitivity (in single-vessel disease) of perfusion imaging. There
      is a definite 'learning curve' for stress echo--both in the practice of image
      acquisition and in interpretation. The choice between these two techniques will
      often be determined by local availability and demand. However, the addition of a
      stress echo service to a modern ECG department is likely to be considerably
      cheaper than the cost of a new gamma camera and radio-pharmacy service. A recent
      editorial called for a 'critical reappraisal' of stress echo and its application
      in the UK. The increasing availability of the necessary hardware and software for
      the newer echocardiography machines is likely to accelerate this process in the
      near future. A more recent application for the technique is in the determination
      of contractile reserve and 'viability' in patients with poor LV function and IHD,
      using low-dose dobutamine regimens. Stress echocardiography is therefore likely
      to occupy an expanding role in the management of patients with coronary artery
      disease, as an adjunct to the exercise ECG.

PMID- 8542260
TI  - A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube
      defects.
AB  - It is now well-established that folic acid, taken peri-conceptionally, can reduce
      the risk of neural tube defects (NTDs). Recent work has demonstrated that an
      abnormality of homocysteine metabolism is a critical factor. The gene for 5,10
      methylenetetrahydrofolate reductase, an enzyme important in homocysteine
      metabolism, was studied in relation to NTDs. To determine the frequency of the
      allele for the thermolabile form of the reductase, DNA samples were collected
      from people with NTDs, parents of people with NTDs, and normal controls. Of 82
      people with NTDs, 15 (18.3%) were homozygous for the abnormal, thermolabile
      allele. This was significantly higher (p = 0.01) than the rate of 6.1% in the
      control population (odds ratio 3.47, 95% CI 1.28-9.41). This is the first
      specific genetic abnormality to be identified in NTDs. It explains the
      association between some NTDs and elevated homocysteine, given that the reductase
      is important in homocysteine metabolism. It also explains how folic acid
      supplementation prevents some NTDs, by overcoming a partial block in the
      conversion of 5,10 methylenetetrahydrofolate to 5 methyltetrahydrofolate. Genetic
      screening could identify women who will require folic acid supplements to reduce
      their risk of having a child with an NTD.

PMID- 8542261
TI  - Brainstem perfusion is impaired in chronic fatigue syndrome.
AB  - We looked for brain perfusion abnormalities in patients with myalgic
      encephalomyelitis/chronic fatigue syndrome (ME/CFS). An initial pilot study
      revealed widespread reduction of regional brain perfusion in 24 ME/CFS patients,
      compared with 24 normal volunteers. Hypoperfusion of the brainstem (0.72 +/- 0.05
      vs. 0.80 +/- 0.04, p < 0.0001) was marked and constant. We then tested whether
      perfusion to the brainstem in ME/CFS patients differs from that in normals,
      patients with major depression, and others with epilepsy. Data from a total of
      146 subjects were included in the present study: 40 normal volunteers, 67
      patients with ME/CFS (24 in the pilot study, 16 with no psychiatric disorders, 13
      with ME/CFS and depression, 14 with ME/CFS and other psychiatric disorders), 10
      epileptics, 20 young depressed patients and 9 elderly depressed individuals.
      Brain perfusion ratios were calculated using 99Tcm-hexamethylpropylene amine
      oxime (99Tcm-HMPAO) and single-photon emission tomography (SPET) with a dedicated
      three-detector gamma camera computer/system (GE Neurocam). Brain-stem
      hypoperfusion was confirmed in all ME/CFS patients. Furthermore, the 16 ME/CFS
      patients with no psychiatric disorders and the initial 24 patients in the pilot
      study showed significantly lower brainstem perfusion (0.71 +/- 0.03) than did
      depressed patients (0.77 +/- 0.03; ANOVA, p < 0.0001). Patients with ME/CFS have
      a generalized reduction of brain perfusion, with a particular pattern of
      hypoperfusion of the brainstem.

PMID- 8542262
TI  - Antigen specificity in hydralazine associated ANCA positive systemic vasculitis.
AB  - The anti-hypertensive agent hydralazine can cause a lupus-like syndrome
      characterized by serosal inflammation, arthralgias and rashes. The kidneys
      however are usually spared. The condition is characterized by circulating immune
      complexes and antinuclear antibodies, whilst antibodies against double-stranded
      DNA are rare. Hydralazine can also cause a systemic vasculitis with a pauci
      immune rapidly progressive glomerulonephritis, which is associated with
      autoantibodies directed against components of the neutrophil cytoplasm. In this
      study, ten patients with hydralazine-induced vasculitis had antibodies with
      specificities for both myeloperoxidase and lactoferrin. We suggest that this
      particular pattern of autoantibodies, together with antibodies with reactivity
      against nuclear components including double-stranded DNA, are characteristic
      findings in hydralazine-induced vasculitis. In addition, renal involvement
      appears to be more common in this group of patients with vasculitis than in those
      with the lupus-like syndrome.

PMID- 8542263
TI  - Clinical features and outcome of patients with thin and ultrathin glomerular
      membranes.
AB  - There is considerable disagreement regarding the natural history of renal disease
      associated with thin glomerular basement membranes (TGBM). We followed 43
      patients (19 male), mean age 41.6 years (range 19-73) for a mean of 88 months (48
      140). TGBM was recognized in adults when glomerular basement membrane thickness,
      measured from multiple sites in electronmicrographs of renal biopsy tissue as the
      harmonic mean, was < 320 nm. At presentation, 95% had microscopic haematuria, 12%
      macroscopic haematuria, 14% loin pain, 28% proteinuria, and 14% hypertension.
      There was no difference in GBM width between the sexes (male 258 nm vs. female
      251 nm) but there was a significant negative correlation between age and GBM
      width (r = -0.53, p < 0.001), with older patients having the thinnest membranes.
      Twenty six patients had ultrathin GBM (< 270 nm), of whom 54% had 3+ haematuria
      vs. 12% of the group with BM > 270 nm (p < 0.01). In the ultrathin group, 71% had
      loss of anionic charge from the GBM, vs. 17% in those with membranes which were
      thin but > 270 nm (p < 0.05). Proteinuria occurred more frequently in those with
      GBM > 270 nm, 65% vs. 8% in the ultrathin group (p < 0.01). Thin GBM were
      associated with a benign prognosis, as after a mean follow-up of 85 months (48
      140), there was no significant change in either serum creatinine or mean arterial
      blood pressure. Patients with ultrathin GBM had greater loss of GBM anionic
      charge, which might result in both an alteration of flow characteristics within
      the glomerular capillaries and also increased fragility of the glomerular
      basement membrane with likelihood of rupture and resultant macroscopic
      haematuria.

PMID- 8542264
TI  - Severe sensory-autonomic neuropathy and endocrinopathy in insulin-dependent
      diabetes.
AB  - A patient developed insulin-dependent diabetes mellitus at the age of 9 years,
      complicated by a sensory/autonomic polyneuropathy which presented with a
      respiratory arrest at the age of 41 years. The neuropathy increased in severity
      over the subsequent two decades. At the age of 52 years she had hypopituitarism,
      hypothyroidism and low normal adrenal function. Autopsy at the age of 59 years
      revealed loss of pituitary tissue with evidence of hypophysitis, a lymphocytic
      thyroiditis and severe adrenal atrophy with lymphocytic infiltration of the
      medulla. The pancreas showed reduced numbers and size of the islets of Langerhans
      with total loss of immunoreactivity for insulin but intact glucagon-producing
      cells. These features are consistent with a type 2 autoimmune polyendocrine
      syndrome, in which lymphocytic hypophysitis has not previously been recorded.
      There was severe loss of myelinated nerve fibres in the sural nerve and rostrally
      accentuated fibre degeneration in the gracile fasciculi, but only mild cell loss
      in the dorsal root ganglia. This combination suggests the presence of a central
      peripheral distal axonopathy. The cervical sympathetic ganglia were severely
      atrophic. Minor inflammatory infiltration was observed in the dorsal root and
      sympathetic ganglia. Significant vascular abnormalities were not present in the
      peripheral nerves. This, and the pattern of nerve fibre degeneration, suggest
      that in this case the neuropathy was likely to have been related to metabolic
      rather than vascular causes. The inflammatory infiltrates in sensory and
      sympathetic ganglia raise the possibility of an autoimmune inflammatory
      contribution to the neuropathy.

PMID- 8542265
TI  - Hepatitis C virus genotype in patients with essential mixed cryoglobulinaemia.
AB  - We studied 54 patients with essential mixed cryoglobulinaemia (EMC), (23 males,
      31 females) mean age 61 years (range 28-77). Forty-one (76%) had type II
      cryoglobulinaemia and 13 (24%) type III. Antibodies to HCV were detectable by
      second-generation ELISA in 49 patients (91%) with confirmed or indeterminate RIBA
      results. HCV RNA was detected by RT PCR using 5' UTR nested primers; HCV
      genotypes 1a, 1b, 2 and 3a were identified by genotype-specific core-region
      nested primers. All patients (49) with antibodies to HCV in their serum were HCV
      RNA positive; 27 (55.1%) had HCV subtype 1b and 21 (42.8%) type 2. In one patient
      the HCV genotype could not be determined. The genotype distribution was not
      different from that found in patients with chronic hepatitis C without
      cryoglobulinaemia. However, the presence of HCV subtype 1b correlated
      significantly with signs of chronic hepatitis and presence of peripheral
      neuropathy. Severity of disease tended to be worse in patients infected with HCV
      subtype 1b, but this was mainly due to liver disease. HCV genotypes may influence
      the clinical expression and, in particular, the severity of liver involvement in
      patients with EMC. Extent and severity of EMC disease in general may also be
      affected by the different HCV genotypes. These findings may have therapeutical
      implications, since the different HCV genotypes respond differently to interferon
      treatment.

PMID- 8542266
TI  - Chronic alcoholic myopathy: diagnostic clues and relationship with other ethanol
      related diseases.
AB  - We report the clinical, laboratory, functional and histological features of 100
      male alcoholic patients of whom 44 had chronic alcoholic myopathy (CAM). We
      evaluated the use of non-invasive tests in detecting CAM, and examined its
      relationship with other ethanol-related diseases such as cirrhosis and
      cardiomyopathy. Of the CAM patients, 24 (55%) presented clinical symptoms of
      myopathy, whereas proximal muscle atrophy was observed in 15 patients (35%).
      Thirty-seven (80%) had significantly decreased muscle strength by myometric
      measurement and 27 (60%) had abnormally increased serum muscle enzymes. In most
      of these patients, the myopathy was classified as mild. The most frequent
      histological findings were myocytolysis, fibre size variability and type II fibre
      atrophy. As there was a good correlation between clinical symptoms, decreased
      muscle strength on myometry and histological evidence of CAM, muscle biopsy may
      be avoidable in some of these patients. Cardiomyopathy and liver cirrhosis were
      more frequent in patients with CAM, and should be checked for in chronic
      alcoholics with skeletal myopathy.

PMID- 8542267
TI  - Liver biopsy in the diagnosis of malignancy.
AB  - In a National Audit of 1500 liver biopsies, 38% were for suspected malignancy. To
      measure their contribution to clinical decisions, the initial diagnoses, biopsy
      diagnoses, final diagnoses, and outcomes were coded by computer and compared.
      Most patients (92%) were investigated for advanced malignancy. The accuracy of
      clinical diagnosis was 78% against final diagnosis. Liver biopsy was seen as
      'confirming' clinical diagnosis overall. This was achieved in 67% (75% with
      ultrasound guidance), and specificity was almost 100%. However, hepatocellular
      cancer was confirmed by biopsy in only 32% and haematological malignancy in 13%
      of suspected cases. Within 3 months, 44% of patients with histological malignancy
      had died. Histological tumour type was not used in 36% of final diagnoses. Of
      patients with a malignancy-negative liver biopsy--showing reactive hepatitis,
      normality, or cholangitis/cholestasis--25%, 47% and 60%, respectively, had final
      malignant diagnoses. In 6% of patients, biopsy showed chronic liver disease. Only
      12% of deaths were autopsied. Liver biopsy contributes very high specificity to
      the diagnosis of malignancy, and detects non-malignant disease. Failure to use
      tumour type may result in sub-optimal therapy. Improving diagnostic practice
      requires more information on outcomes, including autopsies.

PMID- 8542268
TI  - Diagnosis, disease and illness.

PMID- 8542269
TI  - Prospects for using a blood sample in the diagnosis of heart failure.

PMID- 8542270
TI  - Prospects for using a blood sample in the diagnosis of heart failure.

PMID- 8542271
TI  - Irritable bowel syndrome.

PMID- 8542272
TI  - Actin cytoskeleton. Setting the pace of cell movement.
AB  - Eukaryotic cells have many proteins that cap the barbed ends of actin filaments.
      Manipulation of their cellular concentration leads to changes in cell motility
      rates, actin dynamics and signal transduction reactions.

PMID- 8542273
TI  - Transcriptional activation. A holistic view of the complex.
AB  - Recent studies on gene regulation in Saccharomyces cerevisiae support the view
      that eukaryotic activators stimulate transcription by recruiting an RNA
      polymerase II holoenzyme to the promoter in a single step.

PMID- 8542274
TI  - Long-term potentiation. The cell biology connection.
AB  - The relative importance of pre- and post-synaptic mechanisms in long-term
      potentiation has been controversial; a cell-biological approach has now provided
      strong evidence for the involvement of pre-synaptic mechanisms.

PMID- 8542275
TI  - DNA replication. Almost licensed.
AB  - Exact duplication of all the DNA in a cell occurs during each S phase, and only
      once in each cell cycle. Recent results show that conserved proteins of the MCM
      family contribute to these precisely regulated events.

PMID- 8542276
TI  - Cancer. Exploring the bowels of DNA methylation.
AB  - Recent studies of mice lacking methyltransferase, and of genes that modify cancer
      susceptibility, have shed light on the long-standing problem of how DNA
      methylation affects carcinogenesis.

PMID- 8542277
TI  - Re-creating the RNA world.
AB  - Results from in vitro selection experiments can be used to construct and test
      models for the evolution of the RNA world. Surprisingly, the success of selected
      RNAs at binding ligands and catalyzing reactions may make it difficult to
      determine precisely the lineage of molecular fossils, molecules that are believed
      to have survived from the RNA world to the present.

PMID- 8542278
TI  - Hypervariable microsatellites provide a general source of polymorphic DNA markers
      for the chloroplast genome.
AB  - BACKGROUND: The study of plant populations is greatly facilitated by the
      deployment of chloroplast DNA markers. Asymmetric inheritance, lower effective
      population sizes and perceived lower mutation rates indicate that the chloroplast
      genome may have different patterns of genetic diversity compared to nuclear
      genomes. Convenient assays that would allow intraspecific chloroplast variability
      to be detected are required. RESULTS: Eukaryote nuclear genomes contain
      ubiquitous simple sequence repeat (microsatellite) loci that are highly
      polymorphic in length; these polymorphisms can be rapidly typed by the polymerase
      chain reaction (PCR). Using primers flanking simple mononucleotide repeat motifs
      in the chloroplast DNA of annual and perennial soybean species, we demonstrate
      that microsatellites in the chloroplast genome also exhibit length variation, and
      that this polymorphism is due to changes in the repeat region. Furthermore, we
      have observed a nonrandom geographic distribution of variations at these loci,
      and have examined the number and location of such repeats within the chloroplast
      genomes of other species. CONCLUSIONS: PCR-based analysis of mononucleotide
      repeats may be used to detect both intraspecific and interspecific variability in
      the chloroplast genomes of seed plants. The analysis of polymorphic
      microsatellites thus provides an important experimental tool to examine a range
      of issues in plant genetics.

PMID- 8542279
TI  - Imprinted chromosomal regions of the human genome display sex-specific meiotic
      recombination frequencies.
AB  - BACKGROUND: Meiotic recombination events do not occur randomly along a
      chromosome, but appear to be restricted to specific regions. In addition, some
      regions in the genome undergo recombination more frequently in the germ cells of
      one sex than the other. Genomic imprinting, the process by which the two parental
      alleles of a gene are differentially marked, is another genetic phenomenon
      associated with inheritance from only one parent or the other. The mechanisms
      that control meiotic recombination and genomic imprinting are unknown, but both
      phenomena necessarily depend on the presence of some DNA signal sequences and/or
      on the structure of the surrounding chromatin domain. RESULTS: In the present
      study, we compared the frequencies of sex-specific recombination events in three
      chromosomal regions of the human genome that contain clustered imprinted genes.
      Alignment of the genetic and physical maps of the ZNF127-SNRPN-IPW-PAR-5-PAR-1
      region on chromosome 15q11-q13 (associated with Prader-Willi and Angelman
      syndromes) and the IGF2-H19 region on chromosome 11p15.5 (associated with
      Beckwith-Wiedemann syndrome) shows that both regions recombine with very high
      frequency during male meiosis, and with very low frequency during female meiosis.
      A third region around the WT-1 gene on chromosome 11p13 also recombines with
      higher frequency during male meiosis. CONCLUSIONS: The results show that the two
      best-known imprinted regions in the human genome are characterized by significant
      differences in recombination frequency during male and female meioses. A third,
      less well-characterized, imprinted region shows a similar sex-specific bias. On
      the basis of these observations, we propose a model suggesting that the region
      specific differential accessibility of DNA that leads to differential
      recombination rates during male and female meioses also leads to the male- and
      female-specific modification of the signal sequences that control genomic
      imprinting.

PMID- 8542280
TI  - Cooperative binding of Tn3 resolvase monomers to a functionally asymmetric
      binding site.
AB  - BACKGROUND: The inverted repeat is a common feature of protein-binding sites in
      DNA. The two-fold symmetry of the inverted repeat corresponds to the two-fold
      symmetry of the protein that binds to it. In most natural inverted-repeat binding
      sites, however, the DNA sequence does not have perfect two-fold symmetry. Our
      study of how a site-specific recombinase recognizes an inverted-repeat binding
      site indicates that such sequence asymmetry can be functionally important.
      RESULTS: Tn3 resolvase forms two complexes with the 34 base-pair binding site II
      of its recombination region, res. A resolvase monomer first binds at the left end
      of the site; a second monomer then binds cooperatively at the right end. In both
      complexes, the DNA is bent by resolvase. In contrast, the closely related gamma
      delta resolvase binds to site II mainly as a dimer. Insertion of 5 or 10 base
      pairs at the centre of the site does not prevent cooperative binding of two Tn3
      resolvase subunits. The fully occupied site II has a very asymmetric structure.
      Reversal of the orientation of site II in res blocks recombination; thus, its
      asymmetric properties are functionally important. We propose a structure for the
      two-subunit complex formed with site II, based on our results and by analogy with
      the co-crystal structure of gamma delta resolvase bound to res site I.
      CONCLUSIONS: Deviations from perfect inverted-repeat symmetry in a resolvase
      binding site lead to ordered binding of subunits, structural asymmetry of
      resolvase-DNA complexes, and asymmetric function.

PMID- 8542281
TI  - Target DNA capture by HIV-1 integration complexes.
AB  - BACKGROUND: The early steps of human immunodeficiency virus 1 (HIV-1) replication
      involve reverse transcription of the viral RNA and integration of the resulting
      cDNA into a host chromosome. The DNA integration step requires the integration
      machinery ('preintegration complex') to bind to the host DNA before connecting
      the viral and host DNAs. Here, we present experiments that distinguish among
      three possible pathways of target-DNA capture: repeated binding and release of
      target DNA prior to the chemical strand-transfer step; binding followed by
      facilitated diffusion along target DNA (sliding); and integration at the initial
      target-capture site. The mechanism of target-DNA capture has implications for the
      design of gene therapy methods, and influences the interpretation of results on
      the selection of integration target sites in vivo. RESULTS: We present new in
      vitro conditions that allow us to assemble HIV-1 integrase--the virus-encoded
      recombination enzyme--with a viral DNA and then to trap assembled complexes bound
      to target DNA. We find that complexes of integrase and viral DNA do not slide
      along target DNA substantially after binding. We confirm and extend these results
      by analyzing target capture by a hybrid protein composed of HIV-1 integrase
      linked to a sequence-specific DNA-binding domain. We find that the integrase
      domain binds quickly and tightly under the above conditions, thereby obstructing
      function of the fused sequence-specific DNA-binding domain. We also monitor
      target-DNA capture by HIV-1 preintegration complexes purified from freshly
      infected cells. Partially purified complexes commit quickly and stably to the
      first target DNA added, whereas preintegration complexes in crude cytoplasmic
      extracts do not. The addition of extracts from uninfected cells to partially
      purified complexes blocks quick commitment. CONCLUSIONS: Under new conditions
      favorable for the analysis of target-DNA capture in vitro, HIV-1 integrase
      complexes bind quickly and stably to target DNA without subsequent sliding.
      Parallel studies of preintegration complexes support a model in which target-site
      capture in vivo is reversible as a result of the action of cellular factors.

PMID- 8542282
TI  - The role of homeotic genes in the specification of the Drosophila gonad.
AB  - BACKGROUND: In Drosophila, the gonads are composed of two cell populations: the
      germ line, derived from the pole cells, and a somatic component, derived from the
      mesoderm of abdominal segments 5-8. Formation of the gonad requires the function
      of a specific homeotic gene, abdominal-A (abd-A). Other genes of the bithorax
      complex, Ultrabithorax (Ubx) or Abdominal-B (Abd-B), cannot substitute for this
      requirement when abd-A is removed. RESULTS: We show here that, in embryos lacking
      the entire bithorax complex, experimentally induced expression of either ABD-A or
      UBX protein in the mesoderm will rescue the expression of a gonad-specific
      marker, 412 RNA. Ubiquitous expression of these homeotic proteins within the
      mesoderm results in the formation of ectopic gonad tissue anterior to the normal
      location of the gonads. In the absence of any endogenous bithorax-complex gene
      expression, however, mesoderm expressing gonad markers still condenses
      preferentially in the posterior segments of the abdomen, even in the absence of
      pole cells. CONCLUSIONS: The specific requirement for abd-A and not Ubx in gonad
      development does not reflect differences in the properties of the proteins that
      these genes encode, but presumably reflects differences in their regulation. In
      normal development, the restriction of gonad formation to the posterior abdomen
      does not depend on the overlap of abd-A and Abd-B expression, but must depend on
      the regulation of abd-A and Ubx in the sub-population of the mesoderm that forms
      the gonad. Factors other than homeotic gene expression provide some cues that
      direct gonadal mesoderm to condense in the correct location.

PMID- 8542283
TI  - Transgenic expression of human acetylcholinesterase induces progressive cognitive
      deterioration in mice.
AB  - BACKGROUND: Cognitive deterioration is a characteristic symptom of Alzheimer's
      disease. This deterioration is notably associated with structural changes and
      subsequent cell death which occur, primarily, in acetylcholine-producing neurons,
      progressively damaging cholinergic neurotransmission. We have reported previously
      that excess acetylcholinesterase (AChE) alters structural features of
      neuromuscular junctions in transgenic Xenopus tadpoles. However, the potential of
      cholinergic imbalance to induce progressive decline of memory and learning in
      mammals has not been explored. RESULTS: To approach the molecular mechanisms
      underlying the progressive memory deficiencies associated with impaired
      cholinergic neurotransmission, we created transgenic mice that express human AChE
      in brain neurons. With enzyme levels up to two-fold higher than in control mice,
      transgenic mice displayed an age-independent resistance to the hypothermic
      effects of the AChE inhibitor, paraoxon. In addition to this improved scavenging
      capacity for anti-AChEs, however, these transgenic mice also resisted muscarinic,
      nicotinic and serotonergic agonists, indicating that secondary pharmacological
      changes had occurred. The transgenic mice also developed progressive learning and
      memory impairments, although their locomotor activities and open-field behaviour
      remained similar to those of matched control mice. By six months of age,
      transgenic mice lost their ability to respond to training in a spatial learning
      water maze test, whereas they performed normally in this test at the age of four
      weeks. This animal model is therefore suitable for investigating the
      transcriptional changes associated with cognitive deterioration and for testing
      drugs that may attenuate progressive damage. CONCLUSION: We conclude that
      upsetting cholinergic balance may by itself cause progressive memory decline in
      mammals, suggesting that congenital and/or acquired changes in this vulnerable
      balance may contribute to the physiopathology of Alzheimer's disease.

PMID- 8542284
TI  - Developmental signaling. Vertebrate ligands for Notch.

PMID- 8542285
TI  - Cell cycle. The only way out of mitosis.
AB  - The ubiquitination and destruction of cyclins provides the way out of mitosis. A
      multiprotein complex polyubiquitinates cyclin B and promotes the separation of
      sister chromatids.

PMID- 8542286
TI  - Protein kinase C. Seeing two domains.
AB  - Conventional protein kinase Cs have two conserved regulatory domains, C1 and C2,
      shared by many other membrane-interacting proteins. The structures of a C1 and a
      C2 domain provide insights into how they function.

PMID- 8542287
TI  - Retinal development. Waves are swell.
AB  - Waves of spontaneous electrical activity and calcium transients occur in the
      retina during its development. Recent work raises the question of how these waves
      are produced and propagated.

PMID- 8542288
TI  - Membrane traffic. Is the Golgi complex?
AB  - A protein which acts specifically to target vesicles within the Golgi complex,
      rather than to or from it, has recently been described. But does this open the
      way to understanding intra-Golgi membrane traffic?

PMID- 8542289
TI  - Natural killer cells. Right-side-up and up-side-down NK-cell receptors.
AB  - Recent cDNA cloning of the receptors on human natural killer cells for MHC class
      I molecules reveals that human and mouse receptors have inverted structural
      orientations. Are there two distinct receptor systems?

PMID- 8542290
TI  - Cell signalling. Receptor orphans find a family.
AB  - A family of ligands has been identified for the largest group of receptor protein
      tyrosine kinases--the hitherto 'orphan' EPH receptor subfamily--and the functions
      of these receptors and ligands are starting to be elucidated.

PMID- 8542291
TI  - Intracellular signalling. New directions for phosphatidylinositol transfer.
AB  - Newly revealed properties of phosphatidylinositol transfer protein help to
      explain the cellular targeting of lipids involved in signal transduction, and
      indicate that inositol lipids play a part in directing membrane traffic.

PMID- 8542292
TI  - Protein folding. Prolyl isomerases join the fold.
AB  - Cyclophilins have prolyl isomerase activity, but evidence for their suggested
      role in protein folding in cells has been scarce; now they have been found to
      accelerate the folding of mitochondrial precursor proteins.

PMID- 8542293
TI  - Speciation. Down the bottleneck?
AB  - Experiments in which laboratory populations of fruitflies have been repeatedly
      passed through bottlenecks fail to support 'founder-effect' models of speciation.

PMID- 8542294
TI  - Serotonin receptors. Genetic insights into serotonin function.
AB  - Targeted disruption of the genes for the 5-HT1B and 5-HT2C serotonin receptors
      and monoamine oxidase A have confirmed pharmacological experiments and revealed
      unexpected behavioral roles for serotonin.

PMID- 8542295
TI  - The benzodiazepine antagonist CGS 8216 prevents hyperammonemia-induced
      somatostatin receptor reduction in the brain.
AB  - Previous results from our group showed that hyperammonemia decreases the number
      of somatostatin (SS) receptors and that benzodiazepine receptors might regulate
      the number of SS receptors in rat brain. These findings together with the
      supersensitivity of benzodiazepine receptors in the hyperammonemic rat brain
      suggest that benzodiazepine receptors might mediate the effect of hyperammonemia
      on SS receptors. To assess this hypothesis we tested whether 2-phenylpyrazolo[3,4
      c]-quinolin-3(5H)-one (CGS 8216), a benzodiazepine antagonist, prevented the
      effect of ammonium acetate on rat brain SS receptors. Administration of ammonium
      acetate (5 mmol/kg, i.p.) for 7 days did not affect the levels of somatostatin
      like immunoreactivity but decreased the number of SS receptors in synaptosomes
      from the frontoparietal cortex and hippocampus without affecting their apparent
      affinity. This decrease could be blocked by the concomitant administration of CGS
      8216 (10 mg/kg, i.p.). The benzodiazepine antagonist alone had no observable
      effect on the somatostatinergic system. These results suggested that the effect
      of hyperammonemia on SS receptors could be mediated, at least in part, through
      the benzodiazepine receptors.

PMID- 8542296
TI  - Modulatory effects of acute ethanol on metabotropic glutamate responses in
      cultured Purkinje neurons.
AB  - Ethanol has been shown to affect several transmitter- and voltage-gated channels
      in the brain, although little attention has focused on potential interactions
      between ethanol and metabotropic glutamate receptors (mGluRs). This is of
      interest as mGluRs are now recognized to be important components of synaptically
      mediated responses, including short- and long-term changes in the efficacy of
      neurotransmission. Cerebellar Purkinje neurons are sensitive to the effects of
      ethanol and express high levels of mGluRs. We made extracellular recordings from
      cerebellar Purkinje neurons at 21-37 days in culture to examine the effect of
      ethanol on mGluR-mediated responses. mGluRs were activated by pressure ejection
      of 300 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a
      selective agonist of mGluRs, or 5 microM quisqualate (Quis). As Quis activates
      both ionotropic and metabotropic glutamate receptors, 50 microM 6,7
      dinitroquinoxaline-2,3-dione (DNQX) was used to block the ionotropic component of
      Quis-mediated responses. Both ACPD and Quis produced biphasic changes in firing
      rates consisting of an initial brief excitatory phase (5-20 s) followed by a
      prolonged inhibitory phase (10 s to 2.5 min), and induced the generation of
      bursts. Addition of 33 mM (150 mg%) ethanol to the recording medium had little
      effect on ACPD-mediated responses. In the presence of 66 mM (300 mg%) ethanol,
      however, ACPD-mediated responses exhibited an increase in the total response
      duration, with no change in the percent excitation or the induction of bursts as
      compared to controls. On the other hand, 66 mM ethanol decreased Quis-induced
      burst activity, while having no effect on the percent excitation or the total
      response duration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542297
TI  - Cannabinoids selectively decrease paired-pulse facilitation of perforant path
      synaptic potentials in the dentate gyrus in vitro.
AB  - Perforant path synaptic potentials recorded from the outer molecular layer of the
      dentate gyrus were tested for paired-pulse potentiation and stimulus sensitivity
      in the presence and absence of the potent cannabinoid receptor ligand, WIN 55,212
      2. Extracellular perforant path synaptic potential amplitudes were increased by
      51% in 2 mM Ca2+ medium and 60% in 3 mM Ca2+ medium at a conditioning-test (C-T)
      interval of 10 ms, decreasing to 10-15% facilitation at an 80 ms C-T interval.
      Exposure to the potent cannabinoid receptor ligand WIN 55,212-2 produced a marked
      and dose-dependent reduction in the amplitude of the facilitated perforant path
      synaptic potentials. Maximum paired-pulse facilitation was reduced to 35% and 25%
      in 2.0 and 5.0 microM WIN 55,212-2 respectively. The effect was selective for
      potentials facilitated at C-T intervals of 10-60 ms. Input/output (I/O) curves of
      perforant path field potentials were shifted to the right in a dose-dependent
      (2.0 and 5.0 microM) manner by WIN 55,212-2. Significant differences in peak
      amplitudes of perforant path potentials were obtained at all suprathreshold
      stimulus intensities. A comparison of WIN 55,212-2 (5 microM) with the GABAB
      receptor agonist baclofen (200 microM) showed that when both drugs were
      administered independently each produced similar decreases in perforant path
      paired-pulse potentiation. However when administered together at these
      concentrations baclofen and WIN failed to potentiate each other, suggesting
      nonadditivity due to effects on a common process.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8542298
TI  - Localized alterations in pre- and postsynaptic serotonin binding sites in the
      ventrolateral prefrontal cortex of suicide victims.
AB  - Altered serotonin indices have been reported in the brain of suicide victims. We
      sought to localize the changes in presynaptic and postsynaptic serotonin
      receptors and identify an area of prefrontal cortex that may influence suicide
      risk. Quantitative autoradiography was performed in coronal sections of
      prefrontal cortex to determine whether serotonin 5-HT1A receptor (postsynaptic in
      cortex) and serotonin transporter (presynaptic) binding are different in suicide
      victims compared to matched controls. 5-HT1A receptor binding was higher in 85 of
      the 103 sampled areas in the suicide group (n = 18 pairs; P < 0.0001). The
      increase ranged from 17 to 30%. The increase was more pronounced in the
      ventrolateral prefrontal cortex. Serotonin transporter binding was found to be
      lower in the suicide group in all but one of the 43 sampled regions (n = 22
      pairs; P < 0.0001). The reduction in binding was most pronounced in the
      ventrolateral prefrontal cortex, where the difference between suicides and
      controls ranged between 15 and 27%. Serotonin transporter and 5-HT1A binding were
      negatively correlated (r = -0.35 to -0.44, P = 0.04 to 0.007) within the same
      brain areas, suggesting common regulatory factors with opposite effects on
      binding to the two receptors. We conclude that suicide victims have an
      abnormality in the serotonin system involving predominantly the ventrolateral
      prefrontal cortex, and hypothesize that the serotonergic dysfunction in this
      brain region contributes to the risk for suicidal behavior.

PMID- 8542299
TI  - Effects of administration of cholecystokinin into the VTA on DA overflow in
      nucleus accumbens and amygdala of freely moving rats.
AB  - The carboxyterminal octapeptide of cholecystokinin (CCK-8) coexists with dopamine
      (DA) in mesolimbic neurons of the ventral tegmental area (VTA). In the present
      study, in vivo microdialysis in freely moving rats was used to assess the
      relative effects of sulfated CCK-8 (CCK-8S), unsulfated CCK-8 (CCK-8US) and CCK
      tetrapeptide (CCK-4), focally injected into the VTA, on DA overflow in two
      mesolimbic DA/CCK-8S terminal regions, the nucleus accumbens and the amygdala.
      Consistent with electrophysiological findings, microinjection of CCK-8S, but not
      CCK-8US or CCK-4, elicited increases in DA overflow in both terminal regions. In
      the absence of anatomical evidence of CCK-containing fibers in the VTA region, it
      seems reasonable to conclude that the modulation of terminal DA overflow by CCK
      8S through actions at the somatodendritic region represents a form of
      autoregulation of these cells. Whereas CCK-8US and CCK-4 are preferential CCK-B
      receptor agonists, CCK-8S binds non-selectively to CCK-A and CCK-B receptors.
      Thus, these results implicate CCK-A receptors in the stimulatory effects of CCK
      8S on VTA DA neurons.

PMID- 8542300
TI  - Changes of growth inhibitory factor after stab wounds in rat brain.
AB  - The growth inhibitory factor (GIF) is a new metallothionein (MT)-like protein
      that is downregulated in Alzheimer's disease (AD) brain. The biological function
      of GIF has not been fully clarified yet. We have raised an antibody to the
      synthetic polypeptide that is specific for rat GIF. The purified antibody reacted
      to recombinant GIF and native rat GIF but not to MT or maltose-binding protein.
      Using the antibody and GIF cDNA probe, we investigated changes of GIF and GIF
      mRNA by Western and Northern blotting techniques in rat brains after stab wounds.
      The levels of GIF and GIF mRNA began to increase 4 days postoperation, reached a
      maximum at 14-21 days and sustained the increased level at least through 28 days.
      While both glial fibrillary acidic protein (GFAP) and GIF were recognized in
      astrocytes, the increases of these 2 proteins after stab wounds showed different
      patterns. The results indicated that GIF could play an important role in the
      repair after brain damage and also produce new insights into the mechanism of
      gliosis investigated mainly from the viewpoint of GFAP.

PMID- 8542301
TI  - c-fos expression in specific rat brain nuclei after intestinal anaphylaxis:
      involvement of 5-HT3 receptors and vagal afferent fibers.
AB  - The c-fos immediate-early gene is acutely induced in brain after various stimuli
      from the digestive tract. 5-HT3 receptors and vagal afferents have been found
      involved in intestinal motor disturbances induced by intestinal anaphylaxis. Our
      aim was to determine whether intestinal anaphylaxis activates brain structures,
      using c-fos expression, and to evaluate the modulation of c-fos induction by 5
      HT3 receptors and vagal afferents. The effects of antigen challenge on intestinal
      motility were evaluated in ovalbumin-sensitized Hooded Lister rats chronically
      fitted with NiCr electrodes in the jejunal wall. Intestinal motility was assessed
      in conscious rats pretreated or not by perivagal capsaicin or a 5-HT3 antagonist
      (ondansetron). In sensitized rats, ovalbumin disrupted for 62.4 +/- 9.5 min the
      jejunal migrating motor complexes (MMC) and an important c-fos expression was
      detected in the nucleus tractus solitarius (NTS), lateral parabrachial nucleus
      (LPB) and paraventricular nucleus of the hypothalamus (PVN). Intraperitoneal
      administration of ondansetron or perivagal capsaicin treatment significantly
      reduced the duration of MMC disruption and attenuated markedly c-fos staining in
      the 3 brain sites. In contrast, intracerebroventricular administration of
      ondansetron significantly reduced jejunal motor alterations but did not diminish
      the c-fos expression, suggesting a role of central 5-HT3 receptors in the
      efferent control of the intestinal disturbances. Blockade of both c-fos
      expression and MMC disruption by systemic ondansetron and by perivagal capsaicin
      indicates that some brainstem nuclei are involved in digestive disturbances after
      intestinal anaphylaxis, and reflects an involvement of peripheral 5-HT3 receptors
      on vagal afferents. The reduction of c-fos staining in NTS as well as in LPB and
      PVN after perivagal capsaicin suggests that the NTS is the primary relay in the
      activation of the central nervous system during intestinal allergic challenge.

PMID- 8542302
TI  - The bidirectional interaction between ventral tegmental rewarding and hindbrain
      aversive stimulation effects in the rat.
AB  - We used the curve-shift procedure in self-stimulating rats to examine the
      interaction of aversive and rewarding electrical stimuli in terms of duration and
      direction. The subjects were implanted with two moveable electrodes, one in a
      region supporting self-stimulation (the ventral tegmental area, VTA) and another
      in a region supporting escape (the nucleus reticularis gigantocellularis, Gi).
      The function relating self-stimulation rate to pulse frequency (RF function) was
      first obtained and then replicated in a condition where each VTA pulse was
      followed 0.2 or 2.0 ms later by a Gi pulse. The intensity of Gi pulses was set at
      a value previously found to elicit escape within less than 5 sec. The following
      observations were made: (1) rats self-stimulated consistently, despite the
      presence of Gi pulses, (2) the presence of Gi pulses shifted the RF function
      rightward (decreased the rewarding efficacy of VTA stimulation), with little
      effect on the maximum rate, (3) after 2 to 5 VTA-Gi self-stimulation sessions,
      the Gi pulses progressively lost their ability to shift the RF function, and (4)
      at the end of testing, escape was no longer detectable using Gi pulses alone. It
      was concluded that (1) the interaction between rewarding VTA and aversive Gi
      stimulation effects is bidirectional, thus suggesting the presence of algebraic
      summation; (2) the effect of Gi on VTA reward is transient whereas that of VTA on
      Gi aversion cumulates and eventually results in total abolition of Gi aversion.
      The present study represents the first account of cumulative and long-lasting
      suppression of aversion following brain stimulation in the rat.

PMID- 8542303
TI  - MPTP- and MPP(+)-induced effects on body temperature exhibit age- and strain
      dependence in mice.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is toxic toward the
      dopaminergic nigrostriatal system of a plethora of species including rodents,
      nonhuman primates and humans. The present study was designed to evaluate if
      systemic administration of MPTP or its metabolite, 1-methyl-4-phenylpyridinium
      ion (MPP+), has significant effects on body temperature (BT) and whether such
      effects might play a role in the neurotoxicity. A single intraperitoneal (i.p.)
      dose of either MPTP (50 mg/kg) or MPP+ (12.5 mg/kg) leads to a decrease in BT in
      both C57BL/6N (C57) and CD-1 mice. The hypothermia induced by MPTP can be blocked
      by pretreatment with deprenyl (30 mg/kg, i.p.), an MAO-B inhibitor. However, the
      hypothermia elicited by MPP+ is refractive to MAO-B inhibition. These findings
      suggest that MPP+ is responsible for the BT reduction and that the primary site
      of action lies outside the blood-brain barrier. An initial hyperthermic phase in
      the CD-1 mice, which leads to the induction of heat shock protein-72 (HSP-72)
      throughout the brain, differentiates their response to MPTP from that of C57
      mice. This initial hyperthermia appears to be protective since its prevention by
      dosing at a low ambient temperature enhances striatal dopamine (DA) depletion in
      CD-1 mice. The temperature effects of both MPTP and MPP+ also display an age
      dependence in the C57 strain of mice, with the magnitude of the effects
      correlating positively with age. However, profound hypothermia could be induced
      by MPP+ in the absence of striatal DA depletion. The latter finding suggests that
      while a positive correlation was found between age and the magnitude of the
      hypothermia, DA depletion and hypothermia are not causally related. The apparent
      protective effect of the initial hyperthermia in the CD-1 strain of mice,
      however, suggests that BT is an important parameter in the neurotoxicity of MPTP.

PMID- 8542304
TI  - Effect of vagal autotransplantation and bifemelane hydrochloride on cholinergic
      markers and event-related potentials in rats with lesions of the nucleus basalis
      magnocellularis.
AB  - In rats lesioned by injecting the ibotenic acid (8 micrograms/site) into the
      unilateral nucleus basalis magnocellularis (NBM), the effect of treatment with
      bifemelane hydrochloride (BIF) or autotransplantation of the vagal nodosal
      ganglion was studied electrophysiologically by serial measurement of the event
      related potential (ERP, P300) for 4 weeks. In addition, the effects on
      cholinergic markers were assessed by determining the specific binding of [3H]QNB
      (quinuclidinyl benzilate) to the muscarinic acetylcholine receptor (mAChR) as
      well as the activity of choline acetyltransferase (ChAT) and acetylcholinesterase
      (AChE). The P300 latency was delayed and its amplitude remained low for 4 weeks
      in NBM-lesioned rats. In contrast, a return to normal occurred after 2-3 weeks in
      rats given daily intraperitoneal injections of BIF (15 mg/kg) and in
      autotransplanted rats. In lesioned rats, the cortical ChAT and AChE activities on
      the affected side did not recover, but the postsynaptic receptor response was
      transiently activated soon after lesioning. BIF increased specific mAChR binding
      (an early increase of affinity and a subsequent increase of receptor density) as
      well as presynaptic ChAT activity. Transplantation achieved the early activation
      of mAChR binding (increased receptor density) and continuously increased ChAT
      activity. Thus, the postsynaptic compensatory receptor mechanism of denervation
      supersensitivity acted as an early response to the depression of presynaptic
      cholinergic activity, but it could not improve the P300 response until the
      subsequent increase of cortical ChAT activity. Improvement of P300 combined with
      cortical cholinergic recovery after nodosal ganglion grafting or administration
      of BIF suggests that the neocortical ACh level may play an important role in
      regulating ERP.

PMID- 8542305
TI  - Extracellular acetylcholine is increased in the nucleus accumbens following the
      presentation of an aversively conditioned taste stimulus.
AB  - To determine if acetylcholine (ACh) is released in the nucleus accumbens in
      response to a conditioned stimulus (CS) that reminds the animal of an aversive
      event, in vivo microdialysis was used to monitor extracellular ACh during
      conditioned taste aversion. Saccharin flavored water (2.5 mM saccharin) was
      paired twice with nausea induced by i.p. lithium chloride (100 mg/kg). This is
      normally sufficient to create an aversion to the taste of saccharin, but instead
      of a preference test, the saccharin solution was squirted directly into the rat's
      mouth via a cheek catheter during nucleus accumbens microdialysis. The result was
      a 40% increase in extracellular ACh. We reported earlier that dopamine changes in
      the opposite direction; it decreases. This suggests that high synaptic ACh and
      low DA are correlated with an aversive state and cessation of behavior.

PMID- 8542306
TI  - Intracerebroventricular administration of neuropeptide Y inhibits release of
      noradrenaline in the hypothalamic paraventricular nucleus caused by manual
      restraint in the rat through an opioid system.
AB  - Intracerebroventricular injection of 1.5 micrograms neuropeptide Y (NPY) had no
      effect on basal release of noradrenaline (NA) in the hypothalamic paraventricular
      nucleus (PVN), measured by intracerebral microdialysis in the rat. However, it
      blocked the increase in NA release caused by manual restraint but not that by
      tail-pinch, and the effect was blocked by naloxone (1.0 mg/kg body weight). Thus,
      NPY attenuates NA release in the PVN by a painless stressor, such as manual
      restraint, through an opioid system.

PMID- 8542307
TI  - In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in
      rats: effects of repeated sampling.
AB  - Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF)
      withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the
      hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and
      again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were
      similar in the latter. However, when ECF was sampled at 3 h and again 7 days
      after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days
      when compared to all other intervals. These results demonstrate how the
      relationships between Il-1 beta measured in ECF and the conditions of measurement
      appear to be integral parts of a whole intracerebral system: cytokine
      concentrations appear to be inextricably bound to intrahypothalamic conditions
      created by the sampling device presence and frequency of use.

PMID- 8542308
TI  - Estrogen receptor immunoreactivity in ferret brain is regulated by estradiol in a
      region-specific manner.
AB  - The effects of estrogen on estrogen receptor (ER) immunoreactivity in the male
      ferret brain were examined. Estrogen treatment reduced the mean number of ER
      immunopositive (ER+) cells/unit area in periventricular preoptic area but
      increased the mean number of ER+ cells/unit area in the medial division of the
      ventromedial hypothalamic nucleus, while having no effect on the number of ER+
      cells/unit area in the lateral VMH and arcuate nucleus. Thus, estrogen regulates
      brain ER immunoreactivity in male ferrets and the direction and magnitude of this
      regulation are brain region-specific.

PMID- 8542309
TI  - Diurnal variations in vasoactive intestinal polypeptide-like immunoreactivity in
      the suprachiasmatic nucleus of congenitally anophthalmic mice.
AB  - The present study has combined recording of circadian locomotor rhythms with
      light microscopic immunocytochemistry for vasoactive intestinal polypeptide (VIP)
      in the suprachiasmatic nucleus (SCN) of congenitally anophthalmic mice. These
      mice, which never develop retinae or optic nerves and do not perceive light, are
      thus in constant darkness. Our data show a circadian rhythm in expression of VIP
      in the SCN of anophthalmic mice--expression is maximal during late subjective
      night/early subjective day and minimal in late subjective day/early subjective
      night. These observations support the hypothesis that expression of VIP is
      related to regulation of circadian rhythms by the SCN.

PMID- 8542310
TI  - Acute depletion of serotonin down-regulates serotonin transporter mRNA in raphe
      neurons.
AB  - Serotonin transporter (5-HTT) mRNA and 5-HTT sites were measured 3 days after
      treatment with p-chlorophenylalanine, a tryptophan hydroxylase inhibitor. While 5
      HTT mRNA levels decreased (P < 0.001) in the dorsal raphe nucleus, 5-HTT binding
      sites remained unchanged, suggesting that an acute depletion of 5-HT may induce
      an increase in the turnover of 5-HTT mRNA without affecting protein levels at 3
      days.

PMID- 8542311
TI  - Ascorbate potentiates amphetamine-induced conditioned place preference and
      forebrain dopamine release in rats.
AB  - In order to evaluate the effects of ascorbate, which is known to modulate
      dopamine neurotransmission, on the reinforcing effects of amphetamine, we
      coadministered ascorbate and amphetamine during the acquisition of conditioned
      place preference (CPP) in rats. Our results indicate that 100 mg/kg ascorbate
      potentiates the CPP induced by 0.5 mg/kg, but not 1.0 mg/kg, amphetamine. A
      higher dose of ascorbate (500 mg/kg) did not influence the CPP induced by either
      dose of amphetamine. In vitro release assays revealed that, whereas ascorbate
      alone (0.01-1.0 mM) did not influence striatal dopamine levels, this vitamin
      potentiated amphetamine-induced dopamine release in both the nucleus accumbens
      and neostriatum. Collectively, these results raise the possibility that ascorbate
      potentiates amphetamine-induced CPP by increasing the ability of this
      psychostimulant to release dopamine.

PMID- 8542312
TI  - The activation and nuclear translocation of extracellular signal-regulated
      kinases (ERK-1 and -2) appear not to be required for elongation of neurites in
      PC12D cells.
AB  - The outgrowth of neurites was induced in PC12D cells, a subline of PC12 cells,
      that were treated not only with NGF but also with dbcAMP, staurosporine or bFGF.
      Simultaneous activation and rapid nuclear translocation of MAP kinases (ERK-1 and
      ERK-2) were observed in cells treated with NGF or bFGF. But staurosporine and
      dbcAMP induced no or only slight activation of the kinases. The nuclear
      translocation of the MAP kinases was not induced by the latter agents. These
      observations suggest a close relationship between the activation and the nuclear
      translocation of MAP kinases and, moreover, that stimulation and relocalization
      of MAP kinases might not be required for the outgrowth of neurites from PC12D
      cells. Staurosporine and dbcAMP may stimulate a down-stream step of the NGF
      pathway, or a parallel pathway(s) to the MAP kinase cascade in promoting neurite
      formation from PC12D cells. These agents mimic the effects of NGF in promoting
      neurite outgrowth in cultured sympathetic neurons, but not in conventional PC12
      cells. Because of the similarity between PC12D cells and primed cells, it seems
      possible that activation and nuclear translocation of MAP kinases might be
      required for the transcription-dependent differentiation step but might not be
      necessary for the elongation of neurites at least in response to staurosporine or
      to dbcAMP.

PMID- 8542313
TI  - Corticotropin-releasing factor treatment upregulates interleukin-1 receptors in
      the mouse pituitary: reversal by dexamethasone.
AB  - Intraperitoneal injection of rat/human corticotropin-releasing factor (CRF) (40
      micrograms/kg/0.2 ml of saline) resulted in a dramatic increase in specific
      iodine-125-labeled human interleukin-1 alpha ([125I]IL-1 alpha) binding in the
      male C57BL/6 mouse pituitary at 2 and 6 h after the injection although it did not
      affect [125I]IL-1 alpha binding in the mouse hippocampus, spleen and testis at
      any time after the injection. [125I]IL-1 alpha binding was unchanged at 2 h
      following dexamethasone (DEX) treatment (1 mg/kg/0.2 ml of 4% ethanol-saline) in
      the mouse pituitary and the hippocampus. In contrast, DEX inhibited CRF-induced
      upregulation of IL-1 receptors in the pituitary at 2 h after the injection. These
      data demonstrate complex interactions between CRF and DEX on IL-1 receptors
      during stress.

PMID- 8542314
TI  - Olfactory ensheathing cells do not require L-ascorbic acid in vitro to assemble a
      basal lamina or to myelinate dorsal root ganglion neurites.
AB  - Ensheathing cells reside within both the PNS and CNS portions of the primary
      olfactory pathway and provide a glial covering and support for the unmyelinated
      olfactory axons. In vivo, these ensheathing cells express a mixture of astrocyte
      specific and Schwann cell-specific phenotypic features. When grown in vitro in
      the presence of DRG neurons however, these ensheathing cells were observed to
      myelinate DRG neurites. The purpose of the present study was to determine whether
      ensheathing cells, like Schwann cells, require the addition of ascorbic acid to
      the medium in order to assemble a basal lamina and a myelin sheath. Our findings
      indicate that ensheathing cells can myelinate DRG neurites regardless of whether
      ascorbic acid is included in the growth medium and that these glial cells can
      assemble a basal lamina in the absence of added ascorbic acid. It appears from
      these results that Schwann cells and ensheathing cells have different growth
      media requirements for the assembly of a basal lamina.

PMID- 8542315
TI  - N omega-nitro-L-arginine methyl ester interferes with pentylenetetrazol-induced
      kindling and has no effect on changes in glutamate binding.
AB  - The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide synthase, on seizure development and processes of glutamate
      neurotransmission were studied in the pentylenetetrazol (PTZ)-kindled rats. For
      this purpose, a dose of 10 mg/kg L-NAME was injected prior to the 13 kindling
      stimulations. Eight days after the final injection, glutamate binding to brain
      membranes was measured. It was shown that L-NAME suppressed the kindling
      development significantly. Furthermore, L-NAME-pretreated rats showed lower
      seizure scores in reaction to a challenge dose of PTZ. However, glutamate binding
      was not changed by the pretreatment. The data suggest an involvement of NO in the
      mechanisms related with kindling.

PMID- 8542316
TI  - Nitric oxide is involved in long-term potentiation in the medial but not lateral
      amygdala neuron synapses in vitro.
AB  - Possible involvement of nitric oxide (NO) in the induction of long-term
      potentiation (LTP) in the amygdala was investigated using rat brain slice
      preparations in vitro. The induction of LTP in the medial amygdala was blocked by
      NO synthase inhibitors, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester,
      and an NO scavenger hemoglobin. On the other hand, the lateral amygdala LTP was
      not blocked by inhibition of endogenous NO. These results suggest that endogenous
      NO is involved in the induction of LTP in the medial amygdala but not in the
      lateral amygdala.

PMID- 8542318
TI  - Effects of immobilization on in vivo release of norepinephrine in the bed nucleus
      of the stria terminalis in conscious rats.
AB  - Release of norepinepriine (NE) and its metabolites in the bed nucleus of the
      stria terminalis (BNST) was examined using in vivo microdialysis in conscious
      rats before, during and after 2 h of immobilization. Microdialysate levels of NE
      and of dihydroxyphenylglycol (DHPG) increased by 170-290% above basal levels
      during the 1st h of immobilization and decreased gradually thereafter. In
      contrast, levels of dihydroxyphenylacetic acid (DOPAC) increased gradually over
      the entire period of immobilization, peaking at 110% above baseline levels. These
      findings indicate that in rats a single immobilization is attended by increased
      synthesis, release and reuptake of NE within the BNST. The results are consistent
      with previous findings relating to stress-induced release of NE in the
      hypothalamic paraventricular nucleus, central nucleus of the amygdala and
      cerebral cortex and suggest concurrent noradrenergic activation in several brains
      centers during acute stress.

PMID- 8542317
TI  - Antisense oligodeoxynucleotides against mu- or kappa-opioid receptors block
      agonist-induced body temperature changes in rats.
AB  - PL017 and dynorphin A1-17 were shown previously to cause a marked increase and a
      profound decrease in body temperature (Tb), respectively. In this study, we
      examined whether an antisense (AS) oligodeoxynucleotide (oligo) against cloned mu
      or kappa opioid receptors could block PL017- or dynorphin A-induced body
      temperature changes. Treatment with an AS oligo against mu receptors, but not
      sense (S) oligo, missense (MS) oligo or artificial cerebrospinal fluid (aCSF),
      abolished PL017-induced hyperthermia. In addition, treatment with an AS oligo
      against kappa receptors, but not S oligo, MS oligo or aCSF, greatly attenuated
      dynorphin A-induced hypothermia. This study further supports the notion that mu
      and kappa receptors mediate Tb regulation.

PMID- 8542319
TI  - Ethanol suppresses the induction of long-term potentiation in vivo.
AB  - Long-term potentiation (LTP), a leading neural mechanism of memory, is profoundly
      affected by ethanol in vitro, but ethanol's effect on LTP in vivo has not been
      studied at doses known to impair memory. In this study, LTP was induced in the
      dentate hilus by theta-pattern stimulation of the perforant path. Dentate evoked
      responses were recorded during a 3 h session in which rats pressed a lever on a
      fixed interval (30 s) schedule of reinforcement. Following theta-pattern
      stimulation, rats pretreated with saline had significant LTP that was present
      throughout the session. LTP was measured as an increase in the initial slope and
      the population spike of the evoked response. The potentiation was no longer
      present 24 h after stimulation. Ethanol (0.5 g/kg and 1.0 g/kg) blocked LTP and
      attenuated short-term frequency potentiation in a dose-dependent fashion.
      Although ethanol produced a decrease in rewarded lever pressing, lever pressing
      was not correlated to any measure of the evoked response. Ethanol, when given 60
      min after theta-pattern stimulation, did not alter the expression of LTP. The
      results demonstrate that low doses of ethanol selectively blocked the induction
      of LTP in vivo, an effect that may underlie ethanol's impairment of memory.

PMID- 8542320
TI  - Efferent projections of the olivary pretectal nucleus in the albino rat
      subserving the pupillary light reflex and related reflexes. A light microscopic
      tracing study.
AB  - The olivary pretectal nucleus is a primary visual centre sensitive to luminance
      changes. It is involved in the pupillary light reflex, the consensual pupillary
      light reflex and related reflexes, such as the lid closure reflex whereby
      pupillary constriction takes place. Since the olivary pretectal nucleus is a
      small nucleus, previous studies using degeneration, horseradish peroxidase and
      radioactive amino acid tracing were limited regarding to the exclusiveness of the
      projections from the olivary pretectal nucleus. In the present study the position
      of the olivary pretectal nucleus in the rat was first localized by physiological
      recording of the neurons upon luminance stimulation. Subsequently, an anterograde
      tracer Phaseolus vulgaris leucoagglutinin was injected iontophoretically. This
      allows a much more precise localization of the olivary pretectal nucleus
      projections. Ascending and descending pathways originating from the olivary
      pretectal nucleus were observed. Ascending fibres project bilaterally to the
      intergeniculate leaflet, the ventral part of the lateral geniculate nucleus and
      ipsilaterally to the anterior pretectal nucleus. In addition, contralateral
      projections were observed to the zona incerta and the fields of Forel. Descending
      fibres project bilaterally to the periaqueductal gray, the nucleus of
      Darkschewitsch, the interstitial nucleus of Cajal, the Edinger-Westphal nucleus
      and the intermediate gray layer of the superior colliculus. Also a contralateral
      projection to the oculomotor nucleus and an ipsilateral projection to the pontine
      nucleus and the nucleus of the optic tract were found. Furthermore, the
      contralateral olivary pretectal nucleus received a small projection. Retrograde
      tracing experiments using two fluorescent dyes revealed that the fibres
      projecting to the contralateral olivary pretectal nucleus and to the
      contralateral interstitial nucleus of Cajal are collaterals. The projection from
      the olivary pretectal nucleus to the facial nucleus which has been described to
      receive an input in cats could not be confirmed for the rat. The fact that the
      Edinger-Westphal nucleus, the interstitial nucleus of Cajal and the superior
      colliculus receive an input from the olivary pretectal nucleus suggests that this
      primary visual centre is not only involved in the pupillary light reflex, but
      also in controlling eye and head position and saccadic eye movements. Although
      visual acuity largely depends on receptive field sizes of retinal ganglion cells
      and their central connections, the stronger sympathetic influence during the
      pupillary light reflex in animals with frontally placed eyes compared to animals
      with laterally placed eyes may also contribute to the higher visual acuity in
      animals with frontally placed eyes.

PMID- 8542321
TI  - Efferent synaptic organization of the olivary pretectal nucleus in the albino
      rat. An ultrastructural tracing study.
AB  - In this study an ultrastructural analysis was made of the efferent projections of
      the olivary pretectal nucleus in the rat. The anterograde tracer Phaseolus
      vulgaris leucoagglutinin was injected iontophoretically into the olivary
      pretectal nucleus. Ascending and descending pathways were studied. In the
      descending pathway special attention was paid to the fine structural features of
      the olivary pretectal nucleus efferents projecting to the Edinger-Westphal
      nucleus, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch and the
      periaqueductal gray. The projection to the superior colliculus and the pontine
      nucleus was also studied at the ultrastructural level. All the labeled terminals
      in the descending pathway showed ultrastructurally similar features: clear, round
      vesicles and electron dense mitochondria. The terminals made asymmetric synaptic
      membrane specializations (Gray type I), the postsynaptic profiles were dendritic.
      In the interstitial nucleus of Cajal and the superior colliculus the terminals
      are organized in glomerulus-like structures. The terminals in the descending
      pathway were enwrapped by astrocytic processes, also in the glomerulus-like
      structures. In the ascending pathway the projection to the ventral part of the
      lateral geniculate nucleus was studied. Almost all terminals in the ascending
      pathway showed similar ultrastructural features as in the descending pathway:
      electron dense mitochondria, clear, round vesicles and asymmetric synaptic
      membrane specializations (Gray type I). The terminals are organized in glomerulus
      like structures. To identify the projecting neurons in the interstitial nucleus
      of Cajal and the Edinger-Westphal nucleus, retrograde tracing experiments were
      performed. Therefore the beta subunit of cholera toxin conjugated with
      horseradish peroxidase was injected into the facial nucleus.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8542322
TI  - Depression of LTP in rat dentate gyrus by naloxone is reversed by GABAA blockade.
AB  - Long-term potentiation (LTP) of the lateral perforant path (LPP) to dentate
      granule cell (DGC) synapse is suppressed by the opioid antagonist, naloxone, and
      thus appears to be dependent upon the release of endogenous opioids from the LPP.
      It has been suggested that endogenous opioids enhance LTP by depressing GABAA
      inhibition. As one test of this hypothesis, we determined whether blockade of
      GABAA inhibition would alleviate the naloxone block of LTP in the LPP. Consistent
      with the hypothesis that endogenous opioids enable LTP by disinhibition of the
      DGCs, naloxone no longer blocked LTP in the presence of the GABAA antagonist,
      bicuculline methiodide. Furthermore, although blockade of mu receptors suppressed
      LTP of the slope of the population excitatory potential (pEPSP), blockade of both
      mu and delta opioid receptors was needed to suppress LTP of both the pEPSP and
      the orthodromic population spike (OPS).

PMID- 8542323
TI  - Ornithine decarboxylase activity in vitro in response to acute hypoxia: a novel
      use of newborn rat brain slices.
AB  - In fetal as well as newborn rats, acute hypoxic exposure results in significantly
      elevated brain ornithine decarboxylase (ODC) activity, polyamine concentrations,
      and ODC mRNA. The interpretations of these in vivo hypoxic-induced changes,
      however, are complicated by maternal confounding effects. To test the hypothesis
      that acute hypoxia will also increase ODC activity in vitro, we developed a brain
      slice preparation which eliminates such maternal effects. Sections of whole
      cerebrum, approximately 300-500 microns thick, were made from 3- to 4-day old
      Sprague-Dawley rat pups. The slices were equilibrated for 1 h in artificial
      cerebrospinal fluid (ACSF) continuously bubbled with 95% O2/5% CO2, prior to
      induction of hypoxia. We induced hypoxia by changing the oxygen concentration to
      40%, 30%, 21%, 15%, 10%, or 0% O2, all with 5% CO2 and balance N2. In the
      normoxic control brain slices, low but stable basal ODC activity persisted for up
      to 5 h post-sacrifice. Slices in ACSF treated with bovine serum albumin (BSA), or
      both BSA and fetal bovine serum (FBS), however, showed stable ODC activity values
      2- to 3-fold higher than slices in ACSF alone, for up to 5 h. In response to
      acute hypoxia (i.e., 15, 21, and 30% O2), ODC activity was elevated 1.5- to 2
      fold above control values between 1 and 2 h after initiation of hypoxia.
      Qualitative light and electron microscopic examination of the neonatal brain
      slices following 2 h hypoxic exposure suggested that the great majority of cells
      did not show severe hypoxic damage or necrosis. It was concluded that: (1) in
      neonatal rat brain slices in vitro, stable ODC activity values approximating the
      whole brain ODC activity seen at sacrifice, can be maintained for several hours;
      (2) the in vivo hypoxic-induced increase in ODC activity can be approximated in
      vitro; (3) the neonatal rat brain slice preparation may be an alternative to
      other methods for studying hypoxic-induced ODC enzyme kinetics, or other brain
      enzymes, without maternal confounding effects; and (4) ODC activity may be an
      indicator of active metabolism within the newborn brain slice both in normoxia
      and hypoxia.

PMID- 8542324
TI  - Neurogenic influences on contralateral responses during experimental rat
      monoarthritis.
AB  - Many inflammatory conditions show topographically precise symmetrical responses.
      In this study we assessed vascular and cellular responses of apparently normal
      knees following induction of monoarthritis on the opposite side. A strictly
      localised monoarthritis was induced in the right knee of experimental animals
      using intra-articular latex spheres. In both knee joints bradykinin-induced
      plasma extravasation was significantly enhanced increasing from 0.52 +/- 0.07
      micrograms/ml Evans blue to 0.99 +/- 0.07 micrograms/ml and 0.88 +/- 0.1
      micrograms/ml in the injected and uninjected, contralateral, knees respectively
      (P < 0.05). A bilateral increase in cellularity was also apparent with cell
      counts in the uninjected, and apparently normal, knee increasing from 512 +/- 42
      cells/mm2 to a maximum of 812 +/- 125 cells/mm2 on day 10 (P < 0.05).
      Immunohistological analysis demonstrated that the infiltrating cells in both the
      ipsilateral and contralateral joints were predominantly macrophages. Cell counts
      were not increased in the other peripheral joints. Levels of the sensory
      neuropeptide substance P were significantly elevated in both the ipsilateral and
      contralateral dorsal root ganglia and prior inhibition of small unmyelinated
      nerve activity inhibited the cellular infiltrate on the contralateral side,
      suggesting that the effect was mediated, at least partially, by a specific
      neurogenic pathway. The data suggests the presence of a neurogenic mechanism able
      to induce a topographically precise response. This may serve to upregulate the
      cellular defences of at-risk tissues following a potentially damaging stimulus at
      another site.

PMID- 8542326
TI  - Expression of S100 protein in the vestibular nuclei during compensation of
      unilateral labyrinthectomy symptoms.
AB  - In adult guinea pigs, unilateral labyrinthine lesions were inflicted by
      chloroform injections into the middle ear. Immunoreactivity for S100 protein
      (S100) in the vestibular nuclei was studied during compensation of lesion-induced
      postural asymmetry symptoms, i.e., nystagmus, asymmetrical head position. 1 h
      after unilateral labyrinthectomy, increased levels of astroglial S100
      immunoreactivity were found in the superior vestibular nucleus and in the
      medial/lateral vestibular nucleus border region on the side contralateral to the
      deafferentation. Bilaterally, the astrocytic S100 immunoreaction increased in the
      lateral vestibular nuclei around Deiters neurons. Maximal expression of S100 was
      noted 3 h after the lesion. Subsequently, it diminished. Our data reveal that
      transsynaptically altered neuronal activity induces an astrocytic reaction which
      provides increased levels of S100 to the local neuropil. Calcium and zinc binding
      S100 proteins may play a functional role for the neuroplasticity during
      vestibular compensation.

PMID- 8542325
TI  - Melatonin-induced temperature suppression and its acute phase-shifting effects
      correlate in a dose-dependent manner in humans.
AB  - Melatonin is able to phase-shift the endogenous circadian clock and can induce
      acute temperature suppression. It is possible that there is a direct relationship
      between these phenomena. In a double-blind, placebo-controlled crossover study, 6
      healthy volunteers maintained a regular sleep/wake cycle in a normal environment.
      From dusk until 24:00 h on days (D) 1-4 subjects remained in dim artificial
      lighting (< 50 lux) and darkness (< 1 lux) from 24:00-08:00 h. At 17:00 h on D3
      either melatonin (0.05 mg, 0.5 mg or 5 mg) or placebo was administered. Melatonin
      treatment induced acute, dose-dependent temperature suppression and decrements in
      alertness and performance efficiency. On the night of D3, earlier sleep onset,
      offset and better sleep quality were associated with increasing doses of
      melatonin. The following day, a significant dose-dependent phase-advance in the
      plasma melatonin onset time and temperature nadir (D4-5) was observed with a
      trend for the alertness rhythm to phase-advance. A significant dose-response
      relationship existed between the dose of oral melatonin, the magnitude of
      temperature suppression and the degree of advance phase shift in the endogenous
      melatonin and temperature rhythms, suggesting that acute changes in body
      temperature by melatonin may be a primary event in phase-shifting mechanisms.

PMID- 8542327
TI  - Sodium butyrate induces aberrant tau phosphorylation and programmed cell death in
      human neuroblastoma cells.
AB  - Paired helical filaments, one of the major hallmarks of Alzheimer's disease
      brains at autopsy, consist mainly of aberrantly phosphorylated tau. This aberrant
      tau phosphorylation can be induced in the human neuroblastoma cell line TR14 by a
      hyperstimulating mixture, consisting of nerve growth factor (NGF), db-cAMP,
      gangliosides and sodium butyrate (NaBut) [20,23]. Evidence is presented that
      exposing these cells to increasing concentrations of NaBut alone in the 0.5-2 mM
      dose-range is sufficient to induce aberrant tau phosphorylation within 24 h,
      measured by AT-8 immunocytochemistry and Western blotting. This process is
      associated with increased morphological differentiation. Furthermore, the
      aberrant tau phosphorylation is followed by neurotoxicity. This neurotoxicity has
      features of programmed cell death, such as fragmentation on a DNA agarose gel,
      fragmented nuclei and chromatin condensation and inhibition by the protein
      synthesis inhibitor cycloheximide. The mechanism by which NaBut induces these
      modified tau proteins and neurotoxicity are largely unknown but the data suggest
      an involvement of cytoskeletal proteins.

PMID- 8542329
TI  - Correlating angiograms with CT/MRI scans for radiosurgery.
AB  - A mathematical solution is described to reconstruct 3-D objects in the
      stereotactic space from angiographic, not necessarily perpendicular 2-D
      projections. The mathematical calculation requires 6 markers, whose coordinates
      should be known within the stereotactic frame reference system. This method was
      developed to improve the planning in stereotactic radiosurgery of AVM. An AVM
      nidus can be geometrically described as delineated on plane film angiography.
      This approach provides a more accurate determination of the lesion shape, size,
      angulation and position when using information from stereotactic planar
      angiograms. Further more this technique supports a stereotactically accurate
      projection of the surface volume model of the AVM nidus on to the corresponding
      CT and MRI scans images.

PMID- 8542328
TI  - Acute administration of typical and atypical antipsychotic drugs induces
      distinctive patterns of Fos expression in the rat forebrain.
AB  - Fos expression in the rat brain was investigated by immunohistochemistry after
      i.p. administration of single doses of a wide range of typical neuroleptic
      antipsychotic drugs (including the potent dopamine D2 antagonist haloperidol and
      the mixed monoamine antagonist chlorpromazine) and atypical antipsychotic drugs
      (including the weak dopamine D2 antagonists clozapine and thioridazine, the
      relatively pure D2 antagonist raclopride and the mixed D2 and serotonin S2
      antagonist risperidone). For comparison to the effects of the antipsychotic drugs
      and also because the unique clinical therapeutic effects of clozapine have been
      attributed to S2 blockade, the S2 antagonist ritanserin was also studied. The
      single shared effect of all antipsychotic drugs tested was the induction of
      significantly increased Fos immunoreactivity in the nucleus accumbens (NAc). Fos
      positive neurons in the NAc were mostly localized in patches throughout its
      rostrocaudal extent. Haloperidol, chlorpromazine, raclopride and risperidone all
      significantly increased Fos expression in the medial and lateral striatum. Fos
      positive neurons in the striatum were distributed more lateral than medial and
      declined from rostral to caudal levels. Haloperidol, thioridazine and risperidone
      also markedly increased Fos expression in the lateral septum. Distinguishing it
      from the other neuroleptics, clozapine did not increase Fos expression in the
      lateral striatum, but induced a significant increase in Fos expression in the
      prefrontal cortex. Ritanserin did not induce Fos expression in any brain region
      examined, suggesting that S2 antagonism is not responsible for the effects of
      antipsychotic drugs observed here. Our results suggest that there are distinctive
      patterns of Fos expression in the forebrain induced by typical and atypical
      antipsychotic drugs. Notably, Fos expression in the NAc, as a shared property of
      all the antipsychotic drugs, may be related to the actions mediating the
      therapeutic effects of these drugs in the treatment of psychotic disorders. The
      density of Fos-positive neurons stimulated by antipsychotic drugs in the striatum
      appeared to be correlated with the relative severity of extrapyramidal side
      effects produced by these drugs and may be related to the mechanisms mediating
      these effects.

PMID- 8542330
TI  - Optically-navigable operating microscope for image-guided surgery.
AB  - In computer-assisted surgery (CAS), optical digitizing is state-of-the-art.
      Unfortunately standard navigation instruments, e.g. small, LED-equipped pointers
      are frequently shadowed by the operating microscope when the camera-array is
      ceiling- or rack-mounted. Thus, for microsurgery, a navigation module consisting
      of a reference panel mounted onto the housing of the microscope and an object
      distance measuring unit attached in front of the objective lens was developed. By
      means of this navigation module the microscope can be located in space with an
      accuracy of +/- 1-2 mm. Focusing errors due to the high depth of view of modern
      microscopes and individual refraction anomalies are eliminated by laser distance
      measurement. This device has been clinically tested since September 1994 and a
      typical case is reported.

PMID- 8542331
TI  - Microsurgery of cerebral lesions under stereotactic conditions.
AB  - Microsurgical excision of cerebral lesions was carried out under CT-guided
      stereotactic conditions. For lesions located in critical cortical areas, cerebral
      teleangiography under stereotactic conditions provided the coordinates of the
      vascular elements related to the structures and adjacent to the lesion without X
      ray distortion. Small size cortical and subcortical lesions were targeted using
      the stereotactic biopsy probe as a guide. In twenty-four patients stereotactic
      microsurgery was used for following lesions: 8 cavernomas, 8 metastases, 7
      gliomas, and 1 tuberculoma. Unpredictable permanent neurological complications
      did not occur, but predicted transient impairment after surgery in functional
      territories was tolerated with the complete removal of the lesion. The advantages
      of microsurgery using stereotactic coordinates are: precise knowledge of the
      location of brain structures and exact targeting of intracerebral lesions, better
      evaluation of surgical risks, easy spatial orientation, and minimization of the
      surgical damage to the healthy brain tissue.

PMID- 8542332
TI  - Retrieval of a disconnected ventriculoperitoneal shunt catheter by laparoscopy in
      a newborn child: case report.
AB  - In rare cases the peritoneal catheter of a ventriculoperitoneal shunt dislodges
      from the valve and the peritoneal tube migrates into the peritoneal cavity. For
      retrieval of the free intraperitoneal shunt, tube laparoscopy is the initial
      method of choice.

PMID- 8542333
TI  - Intradural lumbar disc herniations: report of three cases.
AB  - Intradural lumbar disc herniation is a rare pathological entity. Three new cases
      among a series of 5000 lumbar spine operations are added to the about 60 previous
      case reports in the literature. None of our patients had undergone lumbar spine
      surgery before. In one patient the location of the free disc fragment was medial
      within the dural sac; in two patients the free disc fragment had penetrated the
      dural sac from the axilla of the nerve root. Pathogenesis is discussed
      (congenital adhesions of the dura mater to the posterior longitudinal ligament at
      the lower lumbar spine; weakness of the dura mater ventrally and at the axilla of
      the nerve root). By multiplanar MRI, the free disc hernia within the dural sac
      may be shown preoperatively.

PMID- 8542334
TI  - Postero-lateral microsurgical approach to orbital tumors.
AB  - A modification of the lateral orbitotomy is reported for the microsurgical
      approach to tumors located in the posterior intraconal space. The orbital apex is
      entered through a small bone opening on the orbital and temporal portions of the
      greater wing of the sphenoid, with the lesser sphenoidal wing, the orbital plate
      of the frontal bone, and the lateral orbital rim being left intact. This surgical
      technique was employed in 8 cases of pure apical tumors, out of a consecutive
      series of 103 orbital growths. It proved to be reliable with regard to either
      adequate exposure and radical excision of the lesions or low rate of operative
      morbility.

PMID- 8542335
TI  - Usefulness of simulation of surgical approaches to cerebral aneurysms by helical
      scanning CT (HES-CT).
AB  - Using multiplanar reconstruction (MPR) CT imaging method, 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 four aneurysm cases after comparing various
      surgical approaches by this imaging method. It was found that these preoperative
      simulated images were very useful at surgery of complicated aneurysm cases.

PMID- 8542336
TI  - A 23-year-old maintenance employee in a fertilizer manufacturing plant was
      exposed to a high concentration of ammonia vapor after a pipe ruptured.

PMID- 8542337
TI  - Preplacement screening for back injuries and disability.

PMID- 8542338
TI  - Prostate cancer screening in a large corporation population.
AB  - The Polaroid Medical Department conducted a prostate cancer screening program of
      all male employees over the age of 49 years. The screening consisted of a World
      Health Organization (WHO) questionnaire, a digital rectal examination (DRE) by an
      occupational medicine doctor, and a serum prostate-specific antigen (PSA) study.
      There were 2241 eligible employees (males between 50 and 65 years of age). 1219
      (54%) took part in the screening. Thirty-seven PSAs above the 3.9 level were
      found (3%) and were further evaluated with ultrasound and/or biopsy. Twelve
      previously unknown cancers of the prostate (1%) were discovered. The cost of the
      entire program to the Polaroid Medical Department, including ultrasound and
      biopsy studies, was $72,130 ($6,012 per cancer detected). Of the 12 cancers, two
      were discovered by abnormal DRE alone, eight by an elevated PSA alone, and two by
      both an abnormal DRE and elevated PSA. There appeared to be no correlation
      between the WHO symptom score and the detection of prostate cancer. Our final
      conclusion was that a corporate medical department screening for cancer of the
      prostate is both effective and cost efficient.

PMID- 8542339
TI  - Occupational injury and stress.
AB  - A literature search was conducted to identify studies that measured the
      relationship between stress and occupational injury. Studies that provided a
      quantitative measure of stress and occupational injury and a quantitative
      assessment of the relationship between these two factors were selected for this
      review. Twenty studies were identified, and all had P values of less than .05 or
      odds ratios ranging from .3 to 4.6. Twelve of 17 measures had odds ratios greater
      than 1.0. Several factors limit the generalizability of these results, however,
      and these include methodological differences in the assessment of stress and
      injury, study design, and limited representation of occupations.

PMID- 8542340
TI  - An epidemic of occupational allergy to latex involving health care workers.
AB  - IgE-mediated sensitivity to natural rubber latex is being recognized more
      frequently among health care workers. Between January 1990 and June 1993, we
      evaluated 342 consecutive Mayo Medical Center employees who reported symptoms
      suggestive of latex allergy. All were interviewed and underwent puncture skin
      testing with extracts of rubber gloves. In some cases, latex-specific IgE
      antibodies were measured by immunoassay. One hundred four of the 342 employees
      evaluated (30%) were latex-allergic. Risk factors for sensitization included
      frequent use of disposable gloves, presence of prior atopic disease, and prior or
      current hand dermatitis. The peak onset of symptoms occurred in late 1989 and
      early 1990 and did not correlate with a peak in glove usage at our medical
      center, which continued to rise. Most sensitized employees (78%) reported contact
      urticaria from rubber gloves, and over two thirds also experienced allergic
      rhinitis, conjunctivitis, or asthma when working in areas where large numbers of
      gloves were being used. Sixteen episodes of rubber-induced anaphylaxis were
      documented in 12 employees; six episodes occurred after latex skin testing and
      were easily reversed with appropriate therapy. Our findings substantiate a local
      epidemic of latex allergy among medical center employees. Epidemiologic studies
      are needed to assess the effects of various interventions to reduce occupational
      exposure to latex allergens. Although prick skin testing with concentrated latex
      glove extracts presents some risk of systemic reaction, pending availability of
      commercial diagnostic extracts, such testing is generally safe when performed by
      skilled laboratory personnel. Skin testing is warranted to investigate health
      care workers suspected of being latex-sensitive.

PMID- 8542341
TI  - Can cardiovascular load in ergonomic epidemiology be estimated by self-report?
      Stockholm MUSIC 1 Study Group.
AB  - In ergonomic epidemiology exposure to local loads as well as cardiovascular load
      may contribute to general and local fatigue and musculoskeletal disease. Self
      reported exposure is often the only feasible method in large population studies.
      The aim of this study was to evaluate retrospectively self-reported physical
      activity and perceived exertion as estimates of cardiovascular load during
      occupational work. The study population consisted of 39 men, representing 25
      different occupations, and 58 women, representing 28 occupations. Ratings of
      physical exertion (RPE scale) and physical activity (Edholm scale transferred to
      multiples of the basal metabolic rate, METs) at the end of a work shift were
      correlated with the average heart rate during the same work shift. In the male
      population, both RPE ratings and METs correlated significantly (P < .01) with the
      average heart rate. No such correlation was observed in the female population.

PMID- 8542342
TI  - Stomach cancer risk among black and white men and women: the role of occupation
      and cigarette smoking.
AB  - This population-based case-control study assesses the risk of stomach cancer
      among black and white men and women. The association of occupational risk factors
      and cigarette smoking with stomach cancer was analyzed using 739 stomach cancer
      cases and 3750 population controls. Complete occupational and tobacco-use
      histories were obtained by telephone interview. Significant increases in stomach
      cancer were observed among black men (odds ratio [OR] = 2.0), white women (OR =
      1.7), and black women (OR = 1.4) who had ever smoked. The majority of occupations
      with significant increases in risk were among white men and included agricultural
      workers (OR = 2.6), driver sales (OR = 3.8), assemblers (OR = 2.0), mechanics (OR
      = 2.2), and material movers (OR = 2.9). Black women employed as assemblers (OR =
      5.4) and white women employed as food workers (OR = 4.0) also had significant
      ORs. Evaluating occupations with possible dust exposure, we found no association
      between dust exposure and stomach cancer.

PMID- 8542343
TI  - Predictors of blood lead levels in organolead manufacturing workers.
AB  - The relations between recent and cumulative exposure to organic and inorganic
      lead and blood lead levels were examined in 222 organolead manufacturing workers.
      Personal monitoring data grouped by 29 exposure zones were used to derive
      estimates of recent and cumulative occupational exposure. Recent exposure to
      organic lead and recent combined exposure to organic and inorganic lead were
      significantly and positively associated with blood lead levels. Exposure duration
      was found to modify the relation between recent inorganic lead exposure and blood
      lead levels. Age and cigarette smoking were positively associated with blood lead
      levels, whereas alcohol use was associated with lower blood lead levels. This is
      in notable contrast to the influence of alcohol consumption on blood lead levels
      among inorganic lead workers or the general population. Furthermore, the data
      suggested that current alcohol use modified the relation between recent organic
      lead exposure and blood lead levels (P = .08): current alcohol users evidenced
      less of an increase in blood lead levels with increasing recent organic lead
      exposures than did workers who did not currently use alcoholic beverages. The
      data suggest that organic lead exposure affects blood lead levels, probably after
      dealkylation to inorganic lead. The associations with alcohol consumption may be
      evidence for differences in enzyme-mediated metabolism of organolead compounds.
      Finally, the data suggest that recent external lead exposure and internal lead
      stores both influenced blood lead levels in these workers.

PMID- 8542344
TI  - [Alternative methods to animal experimentation. Scientific and ethical problems].
AB  - The alternative methods include all the technologies able to replace animal
      experimentation. This denomination has been much debated and several researchers
      prefer the term of complementary methods. Alternative methods consist mainly of
      methods based on organ and cell culture but also includes cell organelles. These
      methods have been introduced gradually over the years particularly in toxicology
      but also in biology, physiology, pathology and pharmacology. The reasons for this
      development are from technological and ethical sources. This last point was due
      to the consciousness of industrial countries on the animal suffering which is at
      the origin of groups for animal welfare, able to influence european governments.
      The results of the development of the alternative methods are an increase in
      fundamental and applied research under the influence of various organisations
      such as in England: FRAME (Fund for the Replacement of Animals in Medical
      Experimentals), in USA: John Hopkins Center and in ECC: ECVAM (European Center
      for the Validation of Alternative Methods). This last Center is particularly
      devoted to validation which are defined as "the process whereby the reliability
      and relevance of a procedure are established for a particular purpose". This
      involves several stages. Some validations procedures are now in progress mainly
      in the aim of evaluating potential alternative methods to the Draize eye
      irritation test. Alternative methods are able to decrease the use of animal
      experiments and consequently improve animal ethics although they could not
      replace totally animal experiments. However they are complementary and very
      useful for the screening of drugs and mechanistic areas.

PMID- 8542345
TI  - [In vitro cutaneous organogenesis (application to skin grafts)].
AB  - The culture of cutaneous fibroblasts in an environment of collagen results in a
      resistant, three-dimensional culture in which fibroblasts are differentiated.
      This dermal sheet can be covered with an epidermal cell layer which will allow to
      rebuild an in vitro human skin equivalent. This in vitro organogenesis technique
      was used since 1983 to treat burns and children suffering from severe cutaneous
      malformations (giant naevi). The results which were obtained after 33 grafts on
      16 patients show that, if the epidermal graft is essential to preserve patients'
      lives the dermal constituent is also important in the long-term since it induces
      the synthesis, 3 to 6 months later, of numerous elastic fibers which give to the
      graft mechanical properties close to that of the normal skin as well as the
      recovery of a normal micro relief. These cutaneous reconstructions can be
      completed in one or, even better, two stages which enable the successive graft of
      reconstructed dermis and epidermal sheets, the latter obtained in great quantity
      thank's to Grenn's method. The conditions of preparation of these living
      biomaterials require rigorous quality controls. Their further development is of
      great interest since it will improve skin replacement and will be a very
      interesting tool for gene therapy.

PMID- 8542346
TI  - [Activity report for 1994. From the Terminology Group (Commission XVII-French
      language)].

PMID- 8542347
TI  - [Eulogy of Andre Lemaire (1898-1994)].

PMID- 8542348
TI  - [Aging, disease and nerve cell death].
AB  - Apoptosis, or programmed cell death, is characterized by an active
      autodestruction of cells. Several proteins inducing (CED-3) or preventing (CED-9)
      neuronal death have been described in the nematode C. elegans. There is an
      homology between these proteins and Bcl-2 and ICE (Interleukin-1 beta-Converting
      Enzyme) in vertebrates. The cascade of biochemical events leading to this active
      neuronal "suicide" is triggered by initiating factors such as genotoxicity,
      growth factors deprivation, cytokines (TNF alpha). As the molecular mechanisms of
      nerve cell death start to be understood, clinicians and neurobiologists are
      confronted with the difficult problem of pathological aging and neuronal death in
      patients with neurodegenerative disorders compared to normal aging. In order to
      distinguish the biochemical abnormalities underlying dysfunction of neurons
      during aging, neuronal loss during neurodegeneration (Parkinson's disease) and
      nerve cell death, we searched for morphological and biochemical signs of
      apoptosis in dopaminergic neurons of the substantia nigra of parkinsonian
      patients and controls. We found characteristic histopathological features of
      apoptosis in about 5% of dopaminergic neurons in the brain of patients. In
      addition, the presence of TNF alpha receptors and the expression of the gene bcl
      2 were observed in dopaminergic neurons. Thus, apoptosis could represent the
      ultimate step of dopaminergic neuronal degeneration in Parkinson's disease.
      Whether this is also the case in other neurodegenerative diseases still remains
      to be proven. In brief, neurons in the human brain could be classified into three
      categories: those which loose slowly part of their functions but are still spared
      by the process of neuronal death (senescence); those which are lost more rapidly
      than similar effects due to aging (neurodegeneration); a small number of neurons
      which die rapidly through apoptosis. The consequences of such observation may be
      important both for neurobiologists and pharmacologists as the basic mechanisms
      which result in senescence, disease and death of neurons could be different.

PMID- 8542349
TI  - [In the name of Commission VII (Sexually transmissible diseases and AIDS).
      Heterosexual transmission of HIV in France].

PMID- 8542350
TI  - [Surgical treatment of hepatocarcinoma in cirrhosis].
AB  - In 1986, our institution published the first results of surgical resection of
      hepatocarcinoma in cirrhotic patients. The aim of this paper is to present long
      term results of this surgical management. From April 1978 to February 1992, 74
      patients were operated on at the surgical clinic of University Medical Center of
      Rennes (35000) France. There were 60 hepatectomies and 14 transplantations. The
      mean age was 60.2 years +/- 9 years and the sex ratio: 70 males and 4 females.
      The etiology was alcoholic in 43 patients (58%), post hepatitis (B and C) in 22
      patients (30%) and due to hemochromatosis in 9 patients (12%). According to the
      Child Pugh classification, 48 patients were Child A, 11 Child B and one Child C
      in the hepatectomy group and 9 patients Child A and 5 Child B in transplantation
      group. The operative mortality was 10% in hepatectomy group and 35.7% in liver
      transplantation group. Overall survival was 61.8% at 1 year, 47.1% at 2 years,
      38.2% at 3 years and 20% at 5 years. 5 year survival is 21.4% after
      transplantation and 18.5% after resection. This difference is not significant. In
      conclusion, according to 5 years survival and to operative mortality the
      treatment of choice is hepatectomy in HCC in cirrhotic patients. However the best
      treatment is the prevention of cirrhosis.

PMID- 8542351
TI  - [Analgesic effect of morphine and its metabolites administered by an
      intracerebroventricular route].
AB  - Intraventricular morphine administration is indicated, in some selected cases, to
      alleviate intractable cancer pain. Our pharmacokinetics data in cerebro-spinal
      fluid allowed us to formulate the theory of "Front de Recrutement". Then we were
      able to determine in cisternal and ventricular cerebrospinal fluid the morphine 6
      glucuronide concentrations. Morphine 6-glucuronide is the main analgesic
      metabolite of morphine and its presence in cerebro-spinal fluid could be due to a
      metabolism of morphine in the central nervous system. Our animal studies showed
      that the analgesic activity of morphine 6-glucuronide was 27 to 67 times higher
      than that of morphine. By demonstrating the 6-monoacetyl morphine potency
      (analgesic metabolite of heroin that is 20 times more potent than morphine), we
      showed the involvement of the 6 position in the analgesic effect of these
      opioids. When we compared the morphine-6 concentrations in human cerebro-spinal
      fluid with the analgesic potency of this metabolite, the morphine-6 glucuronide
      was responsible of 33% to 67% of the supra-spinal analgesic effect. As heroin,
      morphine must be considered as a precursor whose metabolites have pharmacologic
      effects.

PMID- 8542352
TI  - Squamous cell carcinoma of the canine nasal planum: eight cases (1988-1994).
AB  - Squamous cell carcinoma of the nasal planum was diagnosed in eight dogs between
      March 1988 and January 1994. Epistaxis, sneezing, and ulceration or swelling of
      the nasal planum were the most common presenting complaints. Although no evidence
      of metastasis was identified, the primary tumor in all cases was locally invasive
      with extensive involvement of underlying tissues. Advanced imaging procedures
      performed in three cases indicated that physical examination may underestimate
      the local extent of the neoplasm. Euthanasia was performed in six cases due to
      progressive neoplastic disease with worsening epistaxis and sneezing; the mean
      survival time in these cases was 5.4 months.

PMID- 8542353
TI  - Complications of indwelling, silastic central venous access catheters in dogs and
      cats.
AB  - The records of 35 dogs and two cats with Broviac-Cookea catheters implanted
      during a one-year period at The Ohio State University Veterinary Teaching
      Hospital (OSU-VTH) were reviewed for complications. In 36 patients, the catheters
      were used for daily anesthesia associated with cobalt radiotherapy, and in one
      dog the catheter was used for parenteral hyperalimentation. The catheters were in
      place for a mean of 16.7 days. Complications occurred in five patients and
      included infection or sepsis (n = 3), local abscess formation (n = 1), and local
      induration (n = 1); all the complications resolved with appropriate therapy.
      Broviac-Cooke catheters should be considered for use in dogs and cats requiring
      frequent blood sampling, repeated intravenous access, or in those for which
      routine venous access is difficult or impossible. The complication rate is
      minimal (13%) and is similar to that reported in studies of humans with
      indwelling, silastic catheters.

PMID- 8542354
TI  - Cystic, peritoneal mesothelioma in a dog.
AB  - A 10-year-old, spayed female beagle was presented with a 2.5-year history of
      ascites. The ascitic fluid was a modified transudate with no abnormal cells
      present. Cardiac and hepatic functions were normal. Abdominal ultrasonography
      revealed cystic abnormalities of the peritoneal serosal surfaces. On exploratory
      laparotomy, the parietal and visceral peritonea were covered with variably sized,
      thin-walled cysts containing serous fluid. Histopathological,
      immunohistochemical, and ultrastructural analyses of the lesions were consistent
      with a diagnosis of cystic, peritoneal mesothelioma.

PMID- 8542355
TI  - Presumptive, iatrogenic gastric outflow obstruction associated with prior gastric
      surgery.
AB  - Iatrogenic gastric outflow obstruction in two dogs appeared to be caused by prior
      gastric surgery. The obstructions were believed to be anatomical rather than
      functional based on endoscopic examinations. Initially, the dogs had been
      evaluated and each had received two abdominal surgeries because of
      gastrointestinal bleeding, vomiting, or both. Eventually, both dogs were
      euthanized due to complications arising after attempted surgical correction of
      the iatrogenic obstructions. While gastric surgery commonly is performed, it
      seldom is considered to be a potentially harmful procedure. However, as these
      cases demonstrate, the decision to perform a gastrotomy must be weighed against
      possible risks and complications. Iatrogenic gastric outflow obstruction
      associated with surgery may be prevented by minimizing tissue inversion into the
      gastric lumen when surgery is performed near the pyloric outflow tract.
      Additionally, when large lesions near the pylorus are resected surgically,
      preservation of the continuity of the outflow tract is necessary.

PMID- 8542356
TI  - Exophthalmos associated with frontal sinus osteomyelitis in a puppy.
AB  - A three-month-old, male Great Dane puppy developed progressive left exophthalmos,
      epiphora, and swelling of the left frontal bone. Radiographs revealed
      obliteration of the left frontal sinus by a bone-like density, and lateral sinus
      wall thickening with extension into the left orbit. On surgical exploration and
      trephination, the left frontal sinus was filled with soft bone which contained
      multiple pockets of mucopurulent material. Cytologic examination confirmed the
      presence of a large number of neutrophils, osteoclasts, and osteoblasts; and both
      extracellular and intracellular, filamentous, beaded bacteria. The involved bone
      was debrided, and the defects in the orbital wall and sinus were reconstructed
      successfully with a temporalis muscle flap.

PMID- 8542357
TI  - Closed aortic valvotomy: a retrospective study in 15 dogs.
AB  - The results of closed, transventricular valvotomy in 15 dogs with subvalvular
      aortic stenosis (SAS) were evaluated in a retrospective study. Fourteen dogs
      ranged from five to 10 months of age; one dog was 42 months of age at the time of
      surgery. A combination of physical examination, thoracic radiography,
      electrocardiography, echocardiography, Doppler ultrasonography, and cardiac
      catheterization was used to establish a definitive diagnosis. Of the 15 dogs
      undergoing surgery for SAS, 13 had both two-dimensional (2-D) and M-mode
      echocardiographic examinations; three had successful Doppler aortic blood-flow
      studies; and five had successful cardiac catheterizations with selective
      ventricular angiography and intracardiac pressure measurements. In the five dogs
      undergoing preoperative catheterization, pressure gradient measurements across
      the aortic valve ranged from 58 to 130 mm Hg. Gradients were reduced by 55% (from
      58 to 26 mm Hg), 54% (from 65 to 30 mm Hg), and 30% (from 93 to 65 mm Hg) in
      three dogs measured postsurgically at 2.5 months (n = 2) and four months (n = 1),
      respectively. The 10 surviving dogs that were available for follow-up were free
      of clinical signs of cardiac disease postoperatively.

PMID- 8542358
TI  - Splenic vein thrombosis resulting in acute anemia: an unusual manifestation of
      nephrotic syndrome in a Chinese shar pei with reactive amyloidosis.
AB  - Nephrotic syndrome in a seven-year-old Chinese shar pei resulted in oliguric
      renal failure, coagulopathy, and acute anemia. Renal amyloidosis and widespread
      thromboses were diagnosed postmortem. Splenic vein thrombosis caused significant
      splenic congestion, coagulative necrosis, and acute anemia. Splenic vein
      thrombosis is reported here as an unusual consequence of nephrotic syndrome in
      the dog.

PMID- 8542359
TI  - Ivermectin in the treatment of Physaloptera preputialis in two cats.
AB  - Two mixed-breed cats were examined for intermittent vomiting of several months'
      duration. Adult Physaloptera preputialis nematodes were detected in the vomitus
      and melena was observed in both cases. Clinicopathological abnormalities
      including anemia and eosinophilia were found in one case. Clinical signs resolved
      following anthelmintic therapy with ivermectin (200 micrograms/kg body weight)
      administered subcutaneously.

PMID- 8542360
TI  - Traumatic ear canal separations and para-aural abscessation in three dogs.
AB  - Three dogs were presented for para-aural abscessation. Ear canal separations were
      suspected preoperatively, based on histories of trauma, physical examination
      findings of minimally inflamed external ear canals with abrupt endings, and
      radiographic evidence of discontinuity of the ear canals. Concurrent otitis
      media, based on radiographic findings, was diagnosed in all three dogs.
      Disruptions of the external ear canals were confirmed at surgery, and the dogs
      each responded to total ear canal ablation and lateral bulla osteotomy.

PMID- 8542361
TI  - Concurrent toxoplasmosis and feline infectious peritonitis in a cat.
AB  - A 13-year-old, 4-kg, neutered male Maine coon presented with ascites. Toxoplasma
      gondii tachyzoites were seen within neutrophils and macrophages, and free within
      the abdominal fluid. At necropsy, many abdominal organs were positive for feline
      infectious peritonitis (FIP) antigens using immunohistochemical staining. This
      apparently is the first report of concurrent toxoplasmosis and FIP in a domestic
      cat.

PMID- 8542362
TI  - Estrous length, pregnancy rate, gestation and parturition lengths, litter size,
      and juvenile mortality in the domestic cat.
AB  - Reproductive performance in a feline research colony of 14 queens is reported.
      Average estrous length in 38 cycles was 5.8 +/- 3.3 days, with a range of two to
      19 days. Estrous length in 23 bred cycles was not shorter (p greater than 0.05)
      than in 15 nonbred cycles, suggesting that induction of ovulation does not
      decrease estrous length. Pregnancy rate in 23 bred cycles was 73.9%. Gestation
      length averaged 66.9 +/- 2.9 days with a range of 62 to 71 days (n = 15). Average
      parturition length was 16.1 +/- 14.3 hours (n = 7), with a range of four to 42
      hours. Litter size ranged from one to five kittens, with an average of 3.7
      kittens per litter (n = 15). Percent mortality by eight weeks of age was 29.1%,
      with 4.7% stillbirths.

PMID- 8542363
TI  - Polycythemia vera in a cat and management with hydroxyurea.
AB  - Polycythemia vera (PV) was diagnosed in a four-year-old domestic shorthair
      evaluated for hind-limb ataxia, extension of all claws, and difficulty in jumping
      to elevated surfaces. Mild cardiac hypertrophy also was diagnosed. Initial
      laboratory evaluation revealed polycythemia (packed cell volume [PCV], 75%) and
      normal serum total protein (7.5 g/dl). Definitive diagnosis of PV was reached by
      excluding causes of relative and secondary absolute polycythemia using
      radiography, ultrasonography, and blood gases, and by measuring serum
      erythropoietin concentration by radioimmunoassay (13 mU/ml) and an enzyme-linked
      immunosorbent assay (ELISA) method (8.0 mU/ml). Bone-marrow biopsy revealed
      relative erythroid hyperplasia characteristic of myeloproliferative disease.
      Clinical signs were controlled with hydroxyurea (12.2 mg/kg body weight) and
      occasional phlebotomy. Polycythemia vera is an uncommon feline disease, and
      clinical reports on the use of hydroxyurea to manage the condition in the cat are
      lacking.

PMID- 8542364
TI  - The effect of Acemannan Immunostimulant in combination with surgery and radiation
      therapy on spontaneous canine and feline fibrosarcomas.
AB  - Eight dogs and five cats with histopathologically confirmed fibrosarcomas were
      treated with Acemannan Immunostimulanta in combination with surgery and radiation
      therapy. These animals had recurring disease that had failed previous treatment,
      a poor prognosis for survival, or both. Following four to seven weekly acemannan
      treatments, tumor shrinkage occurred in four (greater than 50%; n = 2) of 12
      animals, with tumors accessible to measurement. A notable increase in necrosis
      and inflammation was observed. Complete surgical excision was performed on all
      animals between the fourth and seventh week following initiation of acemannan
      therapy. Radiation therapy was instituted immediately after surgery. Acemannan
      treatments were continued monthly for one year. Seven of the 13 animals remain
      alive and tumor-free (range, 440+ to 603+ days) with a median survival time of
      372 days. The data suggests that Acemannan Immunostimulant may be an effective
      adjunct to surgery and radiation therapy in the treatment of canine and feline
      fibrosarcomas.

PMID- 8542365
TI  - An analysis of 140 injuries to the superior glenoid labrum.
AB  - Between 1985 and 1993 140 injuries of the superior glenoid labrum were identified
      on arthroscopic evaluation and were recalled from a data bank of 2375 shoulder
      procedures performed during that time. The average patient age was 38 years, and
      91% of the patients were men. The most common problem was pain, with 49% of all
      patients noting mechanical catching or grinding in their shoulders. No
      preoperative imaging modality consistently defined disease in the superior labral
      area. Fifty-five percent of all lesions were type II, 21% were type I, 10% were
      type IV, 9% were type III, and 5% were complex. Twenty-nine percent of lesions
      were associated with a partial-thickness tear of the rotator cuff, 11% with a
      full-thickness tear, and 22% with an anterior Bankart lesion. Twenty-eight
      percent of the superior labral lesions seen were isolated and did not have any
      associated rotator cuff or anterior labral disease. Type I lesions were debrided.
      Fifty-six percent of type II lesions were debrided in conjunction with an
      abrasion of the underlying glenoid rim. More recently suture anchors have been
      used to stabilize type II lesions. Treatment of type III and IV lesions depended
      on the extent of labral tissue disruption and involved either debridement or
      suture repair. Repeat arthroscopies were performed on 18 shoulders. Three of five
      type lesions treated with debridement and glenoid abrasion were healed. Four of
      five type II lesions treated with an absorbable anchor were healed. Three type
      III and one type IV lesion treated with debridement had normal superior labrums.
      Two type IV injuries treated with suture repair had completely healed. Two
      complex type II and III injuries treated with debridement and anchor fixation
      were healed.

PMID- 8542366
TI  - Acromial compromise with use of a transacromial portal: a biomechanical study.
AB  - In an experimental evaluation with 14 paired cadaveric scapulae we found that the
      transacromial arthroscopy portal, used occasionally in the repair of superior
      labral lesions, will reduce the structural integrity of the acromion to
      approximately 60% (range 25% to 85%) of its original strength, thereby placing it
      at increased risk of fracture. These studies provide baseline biomechanical
      information and suggest that limited shoulder activity is indicated after use of
      this portal.

PMID- 8542367
TI  - Cutaneous nerve lesions of the shoulder and arm after arthroscopic shoulder
      surgery.
AB  - Increasing use of shoulder arthroscopy has caused developing awareness of the
      associated complications. A consecutive series of patients who had undergone
      arthroscopic surgery of the shoulder was reviewed. The overall incidence of a
      sensory deficit was 21 (7%) in 304 patients at 2 weeks after operation, and in
      approximately half (3.3%) of these patients this condition was still present at 8
      months' average follow-up. These deficits fell into three distinct patterns,
      suggesting that damage was occurring to three different nerve branches. Most of
      these areas of hypesthesia corresponded to lesions of cutaneous branches of the
      axillary nerve; the most likely cause was direct injury at the portal sites,
      particularly the lateral portal.

PMID- 8542368
TI  - Pioneers of shoulder replacement: Themistocles Gluck and Jules Emile Pean.
AB  - Dr. Jules Emile Pean is widely credited with having performed the first total
      shoulder replacement March 11, 1893, at the Hopital International in Paris.
      However, in his original report Pean refers to the work of Themistocles Gluck as
      being the inspiration for his shoulder prosthesis, a fact understated if not
      completely overlooked during the last hundred years. This article therefore
      attempts to reappraise the relative contributions of these two pioneering
      surgeons to shoulder arthroplasty.

PMID- 8542369
TI  - Biologic resurfacing of the glenoid with hemiarthroplasty of the shoulder.
AB  - A porous-coated humeral head replacement with biologic resurfacing of the glenoid
      was performed in 14 patients between 1989 and 1992. Six of the 14 patients had
      greater than 2 years of follow-up and form the basis of this report. The patients
      ranged in age from 33 to 54 years. Diagnoses were osteoarthritis in one,
      postreconstruction arthritis in four, and posttraumatic arthritis in one. The
      biologic resurfacing was done with either autogenous fascia lata or anterior
      shoulder capsule. All patients were relieved of pain. Average postoperative
      positions were elevation 138 degrees, external rotation 50 degrees, and internal
      rotation to the T12 spinous process. These results represent average increases of
      57 degrees, 45 degrees, and six spinal segments, respectively. No donor site
      complications occurred. With Neer's rating scale there were five excellent
      results and one satisfactory result. We conclude that biologic resurfacing of the
      glenoid appears to improve the results of hemiarthroplasty and may well be the
      procedure of choice for young patients with end-stage glenohumeral arthritis.

PMID- 8542370
TI  - Late prosthetic shoulder arthroplasty for displaced proximal humerus fractures.
AB  - Twenty-three shoulders in 23 patients with failed treatment of three- and four
      part proximal humerus fractures subsequently treated with prosthetic arthroplasty
      were reviewed. The initial treatment was closed in 10 cases and open in 13. The
      complications of treatment included malunions in 17, nonunions in four, traumatic
      arthritis in 14, avascular necrosis in nine, humeral shortening in six, and
      deltoid paresis in four. In 20 cases prosthetic arthroplasty was performed an
      average of 15.8 months after injury. Three other cases had arthroplasty 19, 20,
      and 22 years after the original fracture. Seventeen were treated with a total
      shoulder arthroplasty, and six had a humeral head replacement. Thirteen had a
      tuberosity osteotomy, and eight had lengthening of the subscapularis tendon.
      Prosthetic arthroplasty reduced the shoulder pain in 22 (95%). Average active
      forward elevation increased from 68 degrees to 92 degrees, and active external
      rotation increased from 6 degrees to 27 degrees. After arthroplasty 53% of the
      patients were able to do activities at or above shoulder level compared with 15%
      before arthroplasty. Late surgery for failed early treatment is technically
      difficult, and the results are inferior to those reported for acute humeral head
      replacement. These findings should be considered when treatment is selected for
      acute three- and four-part proximal humerus fractures. Nonetheless late
      arthroplasty is a satisfactory reconstructive option when primary treatment of
      proximal humerus fractures fails.

PMID- 8542371
TI  - Limits imposed on glenohumeral motion by joint geometry.
AB  - Contact of the greater tuberosity against the glenoid raises the question of the
      limits imposed on motion by glenohumeral joint geometry. In 50 cadaveric
      shoulders the arcs of articular cartilage on the humeral head and glenoid in the
      frontal and axial planes were measured or calculated. In the coronal plane the
      humeral heads had an arc of 159 degrees (+/- 8.5 degrees) covered by 96 degrees
      (+/- 8 degrees) of glenoid, leaving 63 degrees (+/- 10 degrees) of cartilage
      uncovered. In the transverse plane the humeral arc of 160 degrees (+/- 11
      degrees) is opposed by 74 degrees (+/- 6 degrees) of glenoid, leaving 86 degrees
      uncovered. The 159 degrees of coronal humeral arc articulating with the
      transverse glenoid has 88 degrees (+/- 9 degrees) of cartilage uncovered. The
      geometry of the glenohumeral joint limits motions that occur in simple arcs. The
      obligate external rotation that occurs in elevation is necessary to make more
      humeral cartilage available for articulation with the glenoid.

PMID- 8542372
TI  - Retroversion of the proximal humerus in relationship to prosthetic replacement
      arthroplasty.
AB  - Arthroplasty of the proximal humerus positions a prosthetic articular surface in
      relation to the humeral canal. Most descriptions of surgical technique recommend
      positioning the humeral component in 30 degrees to 45 degrees of retroversion.
      This study measured retroversion in relationship to the surgically reamed canal
      and introduced a method of measurement pertinent to prosthetic reconstruction.
      The canals of 21 cadaveric humeri were surgically reamed, the articular margins
      of the humeral heads were outlined with steel wire, and the trochlear axes were
      transfixed with Steinman pins. Under fluoroscopy the humeri were rotated on a jig
      that allowed rotation around the reamer and measurement of retroversion relative
      to the plane of the articular surface. Retroversion of the proximal humerus is
      highly variable, ranging in this study from 10 degrees to 55 degrees (mean 29.8
      degrees). Anatomic reconstruction of the retroversion angle must be
      individualized. Palpation of the rotator cuff insertion is recommended prior to
      humeral head resection to avoid inadvertant cuff injury.

PMID- 8542373
TI  - Salvage of failed total elbow arthroplasty.
AB  - We had to revise 14 total elbow arthroplasties, three for infection, six for
      aseptic loosening, four for instability, and one for a failed bearing mechanism.
      All of the infected elbows were converted to resection arthroplasty with
      elimination of infection but with poor function; in one acceptable motion was
      achieved after a fascial arthroplasty. Those that failed aseptically were
      salvaged with reimplantation of other devices, either a custom implant or a
      semiconstrained device, which was also used in those nonconstrained elbows that
      failed because of dislocation. All of the noninfected elbows were successfully
      revised with relief of pain and motion comparable to or better than that present
      before revision.

PMID- 8542374
TI  - Capsular restraints to anterior-posterior motion of the abducted shoulder: a
      biomechanical study.
AB  - Twenty-three fresh-frozen cadaver shoulders free of degenerative arthritis or
      rotator cuff disease were tested biomechanically to quantitate the contribution
      of specific capsular structures to restricting anterior-posterior translation of
      the abducted shoulder. With the glenohumeral joint in 90 degrees of abduction on
      a servohydraulic control testing system, translation was measured in 30 degrees
      of forward flexion (with regard to the coronal plane of the scapula), 0 degree,
      and 30 degrees of extension while a 25 N anterior-posterior load was applied.
      Measurements were taken both in the intact (vented) shoulder and after selective
      cutting of different capsuloligamentous structures was performed. In the intact
      shoulder the largest anterior-posterior translation occurred in 0 degree of
      horizontal flexion and extension with regard to the scapular plane, with equal
      amounts of anterior and posterior translation noted. The primary anterior
      posterior stabilizer of the abducted shoulder is the inferior glenohumeral
      ligament complex. The anterior band is the primary stabilizer in 30 degrees of
      horizontal extension and at 0 degree (neutral). The posterior band is the primary
      stabilizer in 30 degrees of horizontal flexion. This study quantifies for the
      first time the normal amount of anterior-posterior translation in the intact
      cadaveric shoulder model. In addition, it demonstrates the relative role of the
      anterior and posterior band of the inferior glenohumeral ligament complex in
      stabilizing the glenohumeral joint at 90 degrees of abduction, where most
      clinical instability of the shoulder occurs.

PMID- 8542375
TI  - Ganglion cyst of the long head of the biceps.

PMID- 8542376
TI  - Synovial chondromatosis of the subacromial bursa with rotator cuff tearing.

PMID- 8542377
TI  - Glenoid surface contact in total shoulder arthroplasties.

PMID- 8542378
TI  - "Terrible triad" or "unhappy triad"?

PMID- 8542379
TI  - Air pollution and mortality: issues and uncertainties.
AB  - Results from 31 epidemiology studies linking air pollution with premature
      mortality are compared and synthesized. Consistent positive associations between
      mortality and various measures of air pollution have been shown within each of
      two fundamentally different types of regression studies and in many variations
      within these basic types; this is extremely unlikely to have occurred by chance.
      In this paper, the measure of risk used is the elasticity, which is a
      dimensionless regression coefficient defined as the percentage change in the
      dependent variable associated with a 1% change in an independent variable,
      evaluated at the means. This metric has the advantage of independence from
      measurement units and averaging times, and is thus suitable for comparisons
      within and between studies involving different pollutants. Two basic types of
      studies are considered: time-series studies involving daily perturbations, and
      cross-sectional studies involving longer-term spatial gradients. The latter
      include prospective studies of differences in individual survival rates in
      different locations and studies of the differences in annual mortality rates for
      various communities. For a given data set, time-series regression results will
      vary according to the seasonal adjustment method used, the covariates included,
      and the lag structure assumed. The results from both types of cross-sectional
      regressions are highly dependent on the methods used to control for socioeconomic
      and personal lifestyle factors and on data quality. A major issue for all of
      these studies is that of partitioning the response among collinear pollution and
      weather variables. Previous studies showed that the variable with the least
      exposure measurement error may be favored in multiple regressions; assigning
      precise numerical results to a single pollutant is not possible under these
      circumstances. We found that the mean overall elasticity as obtained from time
      series studies for mortality with respect to various air pollutants entered
      jointly was about 0.048, with a range from 0.01 to 0.12. This implies that about
      5% of daily mortality is associated with air pollution, on average. The
      corresponding values from population-based cross-sectional studies were similar
      in magnitude, but the results from the three recent prospective studies varied
      from zero to about five times as much. Long-term responses in excess of short
      term responses might be interpreted as showing the existence of chronic effects,
      but the uncertainties inherent in both types of studies make such an
      interpretation problematic.

PMID- 8542381
TI  - Gene transfer into neurones: from basic applications to gene therapy. Symposium
      proceedings. Cardiff, United Kingdom, 16-18 August 1993.

PMID- 8542380
TI  - Introduction to gene transfer: viral vectors.

PMID- 8542382
TI  - Specific infection of rat neuronal circuits by pseudorabies virus.

PMID- 8542383
TI  - Pseudorabies virus as a transneuronal tract tracing tool: specificity and
      applications to the sympathetic nervous system.
AB  - Because of technical shortcomings, neuroanatomical tract tracing methods have
      been limited in their ability to examine functional pathways. This has been
      particularly true of the study of the sympathetic nervous system. Peripheral
      targets of the sympathetic nervous system are innervated by sympathetic ganglion
      cells which are located in various, discreet ganglia, primarily in the abdomen
      and thoracic cavity. Each ganglion contains neurons innervating multiple targets.
      In turn, each ganglion is innervated by preganglionic motor neurons located in
      the thoracic and lumbar spinal cord. Preganglionic neurons are innervated by
      neurons from the brainstem and hypothalamus, as well as probably by spinal
      interneurons. At each of these sites, the ganglia, the preganglionic nuclei of
      the spinal cord, and the brainstem and hypothalamus, functionally different
      neurons are intermingled. Therefore, placement of a traditional retrograde marker
      (i.e. HRP) in any of those sites would generate retrogradely labeled neurons that
      represent multiple functional pathways, making the study of one functional
      pathway impossible. A transneuronal retrograde tracer could obviate this problem
      by passing the original tracer from the first neuron labeled transsynaptically to
      neurons which synapse on to it. After injection of the transneuronal tracer into
      a peripheral target, the tracer would be transported, first to the ganglion cell,
      then to the preganglionic neurons that innervate the ganglion cell, and then to
      the neurons in the brain that innervate the preganglionic neurons. All the
      neurons labeled would belong to one functional pathway, specifically involved in
      control of that target which was injected. There have been attempts to develop
      such tracers. WGA-HRP, tetanus toxin, and the tetanus toxin C-fragment have been
      used with limited success (1,2,3,4,5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542384
TI  - Neuropeptide gene transfer into neuronal and glial cell lines.
AB  - Procorticotrophin-releasing hormone (ProCRH) is the precursor to the hypothalamic
      neuropeptide CRH(1-41) which mediates the neuroendocrine response to stress. In
      neuroendocrine cells and neurones, peptide hormones and neuropeptides are
      targeted to the dense-core vesicles of the regulated secretory pathway. These
      vesicles are transported to the ends of the cellular processes where they are
      stored until they are released upon an external stimulus. In order to study the
      post-translational processing and intracellular trafficking of neuropeptides in
      neuronal cells we have established stably transfected Neuro2A cells and NG115
      401L cells expressing proCRH. The expression vector used contains glutamine
      synthetase (GS) coding sequences which are used as a dominant selectable marker
      in cells already containing GS genes. The various clonal cell lines isolated
      express different levels of CRH as assessed using a specific radioimmunoassay
      (RIA) thus indicating that the level of expression of the exogenous gene must
      depend upon the site of chromosome integration. Using immunofluorescence
      labelling, we have demonstrated that in Neuro2A and NG115-401L cells proCRH is
      packaged in vesicles which accumulate at the tips of cellular processes.

PMID- 8542385
TI  - Gene transfer in cultured ganglion neurons by DNA/calcium phosphate co
      precipitation and gene activation by NGF signal.
AB  - The co-precipitation of DNA with calcium phosphate has been successfully employed
      to transfect cultured chicken embryonic sensory neurons (DRG). Up to 90% of the
      cultured DRG neurons were transfected by this method. This has allowed a study of
      the intracellular second messengers involved in signal transduction and gene
      activation by NGF in DRG neurons. This method can be used to introduce foreign
      DNA also in rat DRG, striatal and hippocampal neurons in culture.

PMID- 8542386
TI  - Investigation of neuropeptide gene transcription in sensory neurons transfected
      by microinjection of reporter plasmids.

PMID- 8542387
TI  - Gene transfer to sensory neurons using herpes virus vectors.

PMID- 8542388
TI  - Regulation of viral and cellular gene expression in sensory neurons.
AB  - Herpes simplex virus (HSV) establishes latent infections of neuronal cells but
      replicates readily in other cell types. This effect is dependent upon the
      presence of the inhibitory cellular transcription factor Oct-2 in neuronal cells.
      This factor inhibits the viral immediate-early gene promoters by at least two
      distinct mechanisms. The significance of Oct-2 in regulating viral and cellular
      gene expression in sensory neurons is discussed.

PMID- 8542389
TI  - Semliki Forest virus as a tool for protein expression in cultured rat hippocampal
      neurons.
AB  - We use the Semliki Forest Virus (SFV) as a tool for protein expression in primary
      cultures of rat hippocampal neurons. These cells develop in vitro into polarized
      neurons that can be infected with recombinant SFV with an efficiency of 60 - 80%.
      SFV-driven protein expression is detectable within 3-4 hours postinfection, at
      which time the newly-synthesized proteins are mainly present in the cell soma. By
      6 to 8 hours postinfection foreign proteins are detectable in the neurites.
      Protein expression can continue for up to 48 hours. However, after 8 - 10 hours
      infected neurons start to suffer from cytopathic effects as evidenced by a change
      in morphology and detachment from the coverslip. The infection does not seem to
      affect the polarized distribution of proteins. Upon overexpression of rab8, a
      somatodendritic distribution is observed, similar to that of the endogenous
      protein. Therefore, the SFV expression system is suitable for short-term
      expression of proteins and can be used successfully to study the polarized
      distribution of heterologous proteins expressed in cultured hippocampal neurons.

PMID- 8542390
TI  - HSV1 vectors to study protein targeting in neurones: are glycosyl
      phosphatidylinositol anchors polarized targeting signals in neurones?
AB  - In order to characterize protein targeting signals in polarized postmitotic
      cortical neurones in vitro, we have developed recombinant and amplicon type
      vectors derived from herpes simplex virus 1 (HSV1) to transfer genes into these
      cells. We examined the targeting of both bacterial proteins, which lack specific
      targeting signals, as well as recombinant proteins containing mammalian targeting
      sequences, i.e. the sequence encoding for the addition of a glycosyl-phosphatidyl
      inositol (GPI) membrane anchor. Utilizing both HSV1 recombinant and amplicon
      vectors we demonstrate that while a GPI anchor is able to direct a foreign
      protein to the plasma membrane, the recombinant protein is targeted mainly to the
      dendritic, but also to the axonal plasma membrane; i.e. its distribution is not
      completely polarized. Thus, GPI anchors do not function as dominant polarized
      targeting signals in neurones, as they do in polarized epithelial cell lines.

PMID- 8542391
TI  - Long-term expression of genes in vivo using non-replicating HSV vectors.

PMID- 8542392
TI  - Development of herpes simplex virus as a gene transfer vector for the nervous
      system.

PMID- 8542393
TI  - Labelling neural precursor cells with retroviruses.

PMID- 8542395
TI  - Gene therapy for disorders of the CNS.

PMID- 8542394
TI  - Minireview: the herpes simplex virus amplicon--a versatile defective virus
      vector.
AB  - The Herpes simplex virus (HSV) amplicon was designed in our laboratory, as a
      defective virus vector, capable of shuttle delivery of DNA sequences and genes
      from prokaryotic to eukaryotic cells, tissues or organs. The HSV vector was
      termed "amplicon" to delineate the fact that it carried the cloned sequences of
      interest, within amplified concatemeric defective genomes, packaged in HSV
      virions. Employing the replication functions of their helper virus, the amplicons
      are wide tropic vectors, capable of entry, replication, and gene expression in
      varied types of cells, both in vitro, and in vivo. In this brief review, the
      amplicons will be revisited, beginning with studies of the naturally occurring
      defective genomes, where many of the virologic aspects of the system were
      established. Properties of the amplicon system and its components, will be
      enlightened. The cis acting functions required for amplicon propagation will be
      briefly described. This will follow with examples of our studies of prokaryotic,
      viral and eukaryotic DNA sequences, which were amplified and expressed within HSV
      defective genomes. Studies designed to examine the involvement of helper viruses
      will be described, including our analyses of host shutoff mutant helper viruses.
      Finally, recent studies of other laboratories will be reviewed, with emphasis on
      what appears to be the use of amplicons as neurotropic vectors, towards potential
      gene therapy.

PMID- 8542396
TI  - Herpes simplex virus latency in tissue culture cells.
AB  - We have developed tissue culture systems which mimic certain aspects of herpes
      simplex virus (HSV) latency, in order to facilitate molecular studies of the
      phenomenon. The initial approach utilised incubation at 42 degrees C to suppress
      virus replication and establish stable latency after infection of human
      fibroblasts at low multiplicity with HSV-2. Latent virus was reactivated
      efficiently by superinfection of cultures with HSV-1 or human cytomegalovirus.
      Improvement of the system was achieved by use of the HSV-1 mutant in1814, which
      has a 12 base pair insertion in the coding sequences for the transactivating
      protein Vmw65 (VP16). Upon infection with in1814 at 42 degrees, or 37 degrees, it
      was possible to obtain cultures in which up to 21% of cells contained a viral
      genome. More recent modifications include the use of mutant in1820 (a derivative
      of in 1814) and pretreatment of cells with interferon alpha, which enable latency
      to be established in approximately 100% of cells. A system has therefore been
      developed that is suitable for the analysis of gene expression and genome
      structure during latency and reactivation.

PMID- 8542397
TI  - Herpes simplex virus-1 latency and its implications for gene therapy of the
      nervous system.

PMID- 8542398
TI  - Adenovirus mediated gene transfer to the central nervous system.

PMID- 8542399
TI  - Adenovirus-mediated transfer of a human dystrophin gene to skeletal muscle of mdx
      mouse.
AB  - Due to their quiescent nature and spatial complexity, many target tissues for
      gene therapy will require novel strategies. An alternative to ex vivo gene
      transfer, providing many technical advantages and possibly allowing sufficient
      transfer of the therapeutic gene, is direct in vivo delivery of the vehicle. For
      a favorable outcome, this procedure is dependent on a high-titer vector, fully
      competent before post-mitotic cells. In view of the restrictions with the use of
      retroviruses, we investigated the potentials of adenovirus. Adenoviruses have as
      primary targets of infection the differentiated epithelial cell. The large DNA
      genome of the virus hints to a large cloning capacity. Furthermore, the wild type
      adenovirus has been largely used in man as a vaccine against adenovirus-induced
      respiratory disease. Taken together, the biological characteristics of adenovirus
      and the precedent of administration to humans are suggestive of adenovirus-based
      gene therapy for diseases involving a variety of quiescent tissues. The use of a
      replication-defective adenovirus carrying a gene encoding a nuclearly-targeted
      beta-galactosidase Ad.RSV beta gal demonstrated that replication-defective
      adenovirus offers an efficient means to transfer a gene for extended periods of
      time in the liver, muscle, lung and brain (1-6).

PMID- 8542400
TI  - Mucopolysaccharidosis type VII as a model system for gene transfer to the central
      nervous system.

PMID- 8542401
TI  - Stable transfection of embryonal carcinoma cells with MAP1A and MAP1B antisense
      sequences.

PMID- 8542402
TI  - Physical methods of gene delivery using keratinocytes as a target for somatic
      cell gene therapy.

PMID- 8542403
TI  - Transfection of proto oncogene c-jun into a mouse neuroblastoma cell line
      potentiates differentiation.

PMID- 8542404
TI  - TrkA mediates an NGF survival response in NGF-independent sensory neurons but not
      in parasympathetic neurons.
AB  - We have investigated the role of trkA, the tyrosine kinase NGF receptor in
      mediating the survival response of embryonic chicken neurons to NGF. Embryonic
      trigeminal mesencephalic (TMN) neurons, which normally survive in the presence of
      BDNF but not NGF, become NGF-responsive when microinjected with an expression
      vector containing rat trkA cDNA. In contrast, microinjection of CNTF-dependent
      embryonic ciliary neurons with the same construct does not result in the
      acquisition of NGF-responsiveness. RT-PCR shows that injected TMN and ciliary
      neurons do not differ in their ability to express rat trkA mRNA or protein. The
      failure of injected ciliary neurons to show an NGF-promoted survival response is
      not due to absence of the low-affinity NGF receptor, p75, in these neurons.
      Quantitative PCR and immunocytochemistry shows that TMN and ciliary neurons both
      express p75 mRNA and protein. These findings not only provide the first direct
      experimental demonstration of trkA mediating a physiological response in an
      appropriate cell type, i.e. NGF-promoted survival of embryonic neurons, but
      indicate that not all neurons are able to respond to a trkA-mediated signal
      transduction event.

PMID- 8542405
TI  - Retrovirus mediated gene transduction into the vertebrate CNS.

PMID- 8542406
TI  - The effect of neurotrophin-5 on the growth and survival of nigral grafts in a rat
      model of Parkinson's disease.

PMID- 8542407
TI  - Assessment of liposomal transfection of ocular tissues in vivo.
AB  - A possible route to the treatment of inherited retinal degenerations such as
      retinitis pigmentosa (RP) is the application of somatic gene therapy by the
      transfer and expression of corrective functional genes in ocular tissue. Cationic
      liposomes are established vehicles for the delivery and expression of exogenous
      genes in mammalian cells both in vitro and in vivo1. We report here a preliminary
      assessment of liposome-mediated transfer of a plasmid carrying the reporter gene
      lacZ (encoding the enzyme beta-galactosidase) into tissues of the adult rabbit
      eye.

PMID- 8542408
TI  - Nuclear and cytoplasmic localisation of procorticotrophin releasing hormone in
      transfected CHO-K1 cells.

PMID- 8542409
TI  - Effects of basic fibroblast growth factor and gamma interferon on hippocampal
      progenitor cells derived from the H-2Kb-tsA58 transgenic mouse.
AB  - Many workers have immortalised neural precursor cells by applying a variety of
      techniques including transfection and retroviral-mediated gene insertion using a
      variety of oncogenes including c-myc, neu, and the SV40 T antigen. This study
      made use of a conditionally immortalised hippocampal cell population derived from
      the H-2Kb-tsA58 transgenic mouse. In this mouse the tsA58 gene is under the
      control of the H-2Kb major histocompatibility complex class I promoter. Enabling
      the mouse to possess an established integrated copy of the early region of the
      large tumour antigen (TAg) gene from the temperature sensitive simian virus 40
      (SV40) mutant strain tsA58. The H-2Kb promoter used in this insert allows
      expression in many tissues with an up-regulation of its effect produced on the
      addition of interferon, which assists cellular proliferation. The temperature
      sensitive gene allows immortality to be controlled at the permissive temperature
      of 33 degrees C, the non-permissive temperature being 39.5 degrees C4.

PMID- 8542410
TI  - Use of gene transfer to study post-translational modifications of neuropeptides
      in cell lines.

PMID- 8542412
TI  - Transient expression of tagged prion protein (PrP) in a neuronal cell line.

PMID- 8542411
TI  - Transfection with hsp70i protects rat dorsal root ganglia neurones and glia from
      heat stress.
AB  - Studies have shown that the induction of heat shock proteins (hsp's) in the CNS
      is protective against excitotoxicity and correlative evidence also suggest that
      hsp's may be protective against ischemic stress and free radical damage. In
      fibroblasts and Chinese hamster ovary cells expression of hsp70i has been shown
      to be essential if the cells are to survive an heat stress. To investigate the
      effect of constitutive overexpression of hsp72 inducible (hsp70i) in neurones and
      glia we transfected rat dorsal root ganglia (DRG) with a plasmid construct
      containing the human EF-1 alpha-promoter and human hsp70i. The results showed
      that prior transfection with hsp70i protected both neurones and glia from heat
      stress. These data support the hypothesis that overexpression of hsp70i plays an
      important role in enhancing the survival of neuronal cells following stress and
      suggests that the induction of a stress response in the CNS may provide an
      alternative form of treatment for neurodegenerative diseases.

PMID- 8542413
TI  - The extracellular matrix molecule, tenascin is associated with adult rat CNS
      axons regenerating into peripheral nerve grafts.

PMID- 8542414
TI  - Adenovirus vectors to transfer genes into neurones: implications for gene therapy
      of neurological disorders.

PMID- 8542415
TI  - Visualization of receptor coupled phosphoinositide turnover in single neurons and
      a glial cell line in culture.

PMID- 8542416
TI  - Stimulation of neurite growth rat adrenal chromaffin cells infected with a
      defective herpes simplex virus carrying an NGF minigene.

PMID- 8542417
TI  - Real time computerized intracellular calcium ion imaging: a rapid method of
      neuronal receptor evaluation.
AB  - Real time computerized intracellular calcium ion analysis using fura-2-based
      fluorescence imaging has been used to evaluate neurotransmitter receptor function
      in primary cultures of rat hypothalamic neurons and a rat hypothalamic neuronal
      cell line (LT6/4). A wide range of neurotransmitters induced an increase in
      intracellular Ca2+ in cultured hypothalamic neurons. In contrast,
      undifferentiated LT6/4 cells failed to response to 56mM K+ or to a battery of
      neurotransmitters with the exception of histamine (100microM). LT6/4 cells,
      induced to differentiate by prior exposure to dibutyryl cAMP and NGF, responded
      to K+ but lost their responsiveness to histamine. Computerized imaging allowed
      the intracellular Ca2+ response of up to 50 cells to be determined simultaneously
      without resort to complex electrophysiological manipulations or receptor binding
      studies. The assessment of receptor complement and coupling using this technique
      allows large amounts of reproducible data to be rapidly collected from small
      populations of cells.

PMID- 8542418
TI  - Use of HSV-1 amplicon vectors to study RNA and protein targeting in cultured
      hippocampal neurons.

PMID- 8542419
TI  - Retroviruses integrate into post-replication host DNA.

PMID- 8542420
TI  - Transneuronal spread of the pseudorabies virus after injection into the central
      nucleus of the amygdala in the rat.
AB  - The pseudorabies virus (PRV) is a swine alpha herpes virus that is widely used as
      a neural tracer because of its marked neurotropism and transneuronal
      transmissibility (Card et al., 1991, 1992; Strack and Loewy 1990). PRV has been
      used to retrogradely identify spinal cord and brainstem connections to various
      peripheral organs, but few anatomical studies have used CNS inoculation of PRV to
      investigate intrinsic brain connectivity. Improved knowledge of the mode and
      temporal pattern of transneuronal spread is essential for interpretation of PRV
      tracing studies, and is also a prerequisite to the use of this and other herpes
      viruses as vectors in the CNS. This study investigated the distribution of PRV
      labelling in the CNS at various time points after its injection into the central
      nucleus of the amygdala (CA). The results indicate that detection of PRV in a
      retrogradely labelled site at any given time after injection is not only a
      function of the number of synapses in the pathway from the injection site, but is
      also highly dependent on the axon lengths involved, much more than would be
      expected if fast axonal transport were the limiting factor. In addition, the
      window of time during which PRV may be detected in a given site is limited
      ultimately by neuronal destruction.

PMID- 8542421
TI  - A recombinant herpes simplex type 1 virus expressing antisense 5-HT2 receptors.

PMID- 8542422
TI  - Retroviral-mediated gene transfer into early passage cultures of ovine
      neuroectodermal, epithelial and mesenchymal tissues.
AB  - The relative efficiency of retroviral-mediated gene transfer into early passage
      cultures of different tissues of fetal lamb was investigated. Cells which
      originate from different embryonic germ layers showed marked differences in
      infectibility in the descending order: brain (neuroectoderm) > kidney
      (nephrogenic mesoderm) > muscle (somite mesoderm), lung (endoderm) > skin
      (ectoderm). In an attempt to generate immortalized brain cell lines, primary
      cultures were transduced with various oncogenes. A wide variety of
      morphologically distinct, dividing cells, including neurone-like and glial-like
      cells, were obtained using some oncogenes but also using the vector without an
      inserted oncogene.

PMID- 8542423
TI  - Generation of recombinant herpes simplex virus type 1 to be used for automatic
      tract tracing.
AB  - We generated two insertional beta-galactosidase (lacZ) expressing herpes simplex
      virus type 1 (HSV-1) with putative mutations in the UL41 or US5 open reading
      frames. Purified recombinants or wild-type HSV-1 were injected into the left
      adrenal gland of hamsters. Three days later, virus-infected neurons were
      visualized with immunohistochemistry in spinal cord sections from all infected
      hamsters. Neurons were also visualized with X-Gal histochemistry in spinal cord
      sections from hamsters infected with either of the recombinants but not with the
      wild-type virus. Insertional mutagenesis of the HSV-1 genome by lacZ did not
      disrupt the neurotropic properties of the virus. Both recombinant viruses
      transneuronally labelled the central nervous system (CNS) sympathoadrenal
      preganglionic neurons and may be useful for the study of synaptic organization of
      neural circuits. Successful transynaptic transmission of this marker gene into
      CNS neurons from a peripheral organ suggests that other foreign genes may also be
      delivered into CNS neurons using HSV-1.

PMID- 8542424
TI  - CNS tumor therapy by attenuated herpes simplex viruses.

PMID- 8542425
TI  - Defective herpes simplex virus vectors for the study of promoter and gene
      function in the CNS.

PMID- 8542426
TI  - Adeno-associated virus (AAV) as a vector for gene transfer into glial cells of
      the human central nervous system.
AB  - To examine the potential of AAV as a vector for gene transfer in glial cells, an
      established astrocytoma cell line and short-term cultures derived from human
      oligodendroglioma have been coinfected with AAV and helper adenovirus. The level
      of AAV replication in glioma cells was high indicating that they express
      receptors for AAV.

PMID- 8542427
TI  - B-50/GAP-43 expression via a defective herpes simplex virus vector results in
      persistent morphological changes in non-neuronal cells.

PMID- 8542428
TI  - Immunological consequences of HSV-1-mediated gene transfer into the CNS.
AB  - Defective HSV-1 viral vectors were prepared using amplicon methods. The amplicon
      contained the cytomegalovirus immediate-early promoter and the lacZ gene as a
      reporter in addition to the HSV elements required for replication and packaging
      in vitro. Viral vectors were stereotaxically injected into the rat dentate gyrus
      and the resulting expression and immune response were investigated. Beta
      galactosidase activity was detected in several thousand neurons from as early as
      24 hours to as late as 10 days after injection. A significant immune response to
      the vector inoculation developed, which was characterised by diffuse MHC class I
      up-regulation from 48 hours and the infiltration of MHC class II+ cells and
      activated T lymphocytes and macrophages from day 4. These features persisted for
      at least 31 days. Of particular interest was a small group of neurons in the
      posterior hypothalamus which were found bilaterally to express beta
      galactosidase. The immune response at this distant uninjected site was delayed in
      onset but its features were similar to that found at the primary site of
      inoculation.

PMID- 8542429
TI  - Expression of human amyloid precursor proteins in cultured neuronal cells through
      the use of HSV-1 defective vectors.
AB  - Postmortem investigations of Alzheimer's patients reveal senile plaques that
      contain, among other molecules, deposits of beta-amyloid protein. The role of the
      beta-amyloid deposits remains unclear but identification of mutations in the
      amyloid precursor protein (APP) gene within the beta-amyloid portion in
      hereditary forms of the disease provide evidence that these deposits are involved
      in the pathological state. To more fully investigate this hypothesis attempts
      have been made to create transgenic mice to overexpress the beta-amyloid protein
      but these models have not been successful in modeling the disease. We have chosen
      to utilize the HSV-1 defective vector system which allows the expression of
      experimental genes in neuronal cells to overexpress APPC100. We have cloned the
      rat tyrosine hydroxylase (TH) promoter into a defective HSV plasmid. Cloning the
      firefly luciferase gene under the control of the TH promoter (demonstrates that
      the promoter is active after infection of human SY5Y cells or rat PC12 cells. A
      synthetic APP cDNA which represents the last 100 amino acids of the carboxy
      terminus of APP including the beta-amyloid protein was synthesized and inserted
      under the control of the TH promoter. Infection and subsequent nuclease
      protection assays demonstrate expression of the synthetic gene in the infected
      cells. Current research focuses on detection of the expressed protein within the
      infected cells and determination of the time period for continued expression.

PMID- 8542430
TI  - Oxytocin neurones in the supraoptic nucleus (SON) are inhibited by endogenous
      opioids in late pregnant rats.
AB  - Late pregnant rats exhibit endogenous opioid restraint of oxytocin cells since
      i.v. naloxone (NLX opioid antagonist) increases oxytocin (OXT) secretion but OXT
      nerve terminals become desensitised to opioids. We have studied central opioid
      inhibition of OXT neurones in late pregnancy by measuring SON OXT neurones firing
      rate, immediate early gene (Fos) expression and dendritic OXT release under the
      influence of NLX On day 21 of pregnancy NLX strongly potentiated cholecystokinin
      (CCK) excitation of OXT neurones increased Fos protein expression and increased
      intranuclear release of OXT in the SON; NLX was ineffective in virgin rats. The
      data indicate central endogenous opioid inhibition of OXT neurone activity in
      late pregnancy which may restrain premature OXT release.

PMID- 8542431
TI  - Corticotrophin-releasing hormone, proenkephalin A and oxytocin mRNA's in the
      paraventricular nucleus during pregnancy and parturition in the rat.
AB  - Since stress and opioids affect oxytocin secretion we investigated the
      involvement of corticotrophin-releasing hormone (CRH) and enkephalin on the
      regulation of oxytocin production during pregnancy and parturition by measuring
      CRH, proenkephalin A (PENK) and oxytocin mRNA's in the paraventricular nucleus
      (PVN) using quantitative in situ hybridisation. On day 21 of pregnancy and during
      parturition CRH mRNA content and the number of parvocellular neurones expressing
      CRH were significantly decreased but neither PENK nor oxytocin mRNA was altered.
      The suppression of the CRH gene in late pregnancy and parturition may lead to the
      previously reported reduction in stress responses during lactation.

PMID- 8542432
TI  - Lithium regulation of G protein mRNA levels in PC12 and GH3 cells: theoretical
      implications for gene therapy in bipolar illness.

PMID- 8542433
TI  - Genetics of metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the
      deficiency of arylsulfatase A (ASA). The mode of inheritance is autosomal
      recessive. The disease occurs panethnically and its frequency is 1 in 40000. The
      deficiency of the enzyme causes the accumulation of its substrate cerebroside
      sulfate. Since this sphingolipid is mainly found in the myelin membranes the
      disease primarily affects the oligodendrocytes. Patients suffer from a
      progressive demyelination and die due to a variety of neurologic symptoms.
      Clinically the disease is heterogeneous. Depending on the age of onset a late
      infantile, juvenile and adult form can be distinguished. We have cloned the cDNA
      and gene of arylsulfatase A. Several disease causing mutations have been
      identified and a simple genotype phenotype correlation has been revealed.
      Currently we try to develop a mouse model of MLD via homologous recombination in
      embryonic stem cells. The model will allow to elucidate the pathogenesis of the
      disease and to test possible therapeutic approaches.

PMID- 8542434
TI  - Clinical considerations in gene therapy of Huntington's disease.

PMID- 8542435
TI  - Progressive retinal atrophy: a model for retinitis pigmentosa in companion
      animals.
AB  - The generalised progressive atrophies (PRA's) are a heterogeneous group of
      inherited retinopathies in dogs and cats. They show marked similarities to the
      retinitis pigmentosas (RP) in man, as well as to a number of inherited retinal
      degenerations of laboratory rodents. Of the various recessively inherited forms
      of PRA in the dog, that in the Irish setter is due to a nonsense mutation in the
      gene encoding cGMP-PDE-beta subunit. Mutations at this locus are also known to
      cause a proportion of human RP cases. We are interested in applying gene therapy
      to these diseases.

PMID- 8542436
TI  - Intracultural diversity and the sociocultural correlates of blood pressure: a
      Jamaican example.
AB  - Attention to intracultural diversity in anthropological research has increased,
      but the implications of that diversity for research design and data analysis in
      medical anthropology have not proceeded as far. An examination of diversity and
      its use in guiding data analyses is given here, based on the study of blood
      pressure and its social and psychological correlates. It is argued that in the
      specific ethnographic setting of a small West Indian town, social class
      structures the diversity of the meanings of beliefs and behaviors. Diversity of
      meanings, in turn, alters the associations of those beliefs and behaviours with
      blood pressure. Data analyses guided by this orientation demonstrate that the
      social patterning of blood pressure varies between and within social class.
      Specifically, it is shown that one model of social and psychological influences
      on blood pressure applies only to middle-class persons in a small Jamaican
      community and not to lower-class persons. Medical anthropologists need to be more
      sensitive to the range of intracultural diversity and to how that diversity can
      influence the results of research.

PMID- 8542437
TI  - Toward an anthropology of senility: anger, weakness, and Alzheimer's in Banaras,
      India.
AB  - Dementia has seldom been subject to cross-cultural and cross-class analyses that
      localize the obviousness and meaningfulness of its pathology. Fieldwork with old
      persons and their families in four neighborhoods of Banaras, India, stratified by
      class, is presented to suggest the need for an anthropology of senility. The
      centrality of "hot brain"--of anger rather than memory as a fundamental index of
      senile difference--is explored through its differential construction across class
      and gender in these neighborhoods. The hearing of the angry voice is examined in
      relation to local knowledge about weakness, madness, and "sixtyishness" and to
      practices that maintain intergenerational difference through the construction of
      what is here termed a familial body.

PMID- 8542438
TI  - Organ wars: the battle for body parts.
AB  - Transplantation surgeries contribute to conceptions of the body as a collection
      of replaceable parts and of the self as distinct from all but its neural locus.
      There remains substantial cultural resistance to these conceptions, which leads
      the medical community to attempt to link the surgeries to social values that are
      sufficiently powerful to minimize the sense of a disjuncture between traditional
      concepts of personhood and those consistent with transplantation. The controversy
      over how to increase the supply of transplantable organs reveals two
      diametrically opposed sets of values invoked by advocates of transplantation:
      altruism and individual rights. The article analyzes these as the ideological
      equivalents of immunosuppressant drugs, designed to inhibit cultural rejection of
      transplantation and its view of the body.

PMID- 8542439
TI  - Organ transplantation as a transformative experience: anthropological insights
      into the restructuring of the self.
AB  - Transplantation represents in the popular mind the pinnacle of biomedical
      knowledge and skill. Its feasibility depends upon the management of conflicting
      cultural values surrounding death and dying, where diverse parties consider
      bodies and their parts to be personal property, sacred entities, or offerings to
      the common good. Specifically within the specialized transplant community, viable
      organs are scarce, socially valuable resources. The ideology that guides
      transplant professionals, however, is rife with contradictions: close inspection
      reveals unease over definitions of death and rights to body parts. Ideological
      disjunction arises from the competing needs to personalize and to objectify
      organs and bodies. Organ recipients struggle with these contradictory messages as
      they rebuild their sense of self and self-worth following transplantation. This
      transformative process is explored by analyzing professional writings and data
      generated from ethnographic research in the United States. The study ends by
      examining transformed identity as fictionalized and extended biography.

PMID- 8542440
TI  - Transcending mortality: organ transplants and the practice of contradictions.

PMID- 8542441
TI  - Organ transplantation (re)examined?

PMID- 8542442
TI  - Bioethnography: fieldwork in the lands of medical ethics.

PMID- 8542443
TI  - Motor proteins 1: kinesins.
AB  - Progress regarding the kinesins is now being made at a rapid and accelerating
      rate. The in vivo-functions, and biophysical and enzymatic properties of kinesin
      itself are being explored at ever increasing levels of detail. The kinesin
      related proteins now number several dozen, and although more is known about
      primary structure than function for most of the proteins, this trend is already
      reversing. For example, knowledge about the kinesin-related protein, ncd, is
      expanding rapidly, and more is already known about its three-dimensional
      structure than is known for kinesin heavy chain. This volume presents a
      comprehensive review of the major published works on kinesin and kinesin-related
      proteins. Hopefully, this manuscript will complement other recent review articles
      [17, 20, 25, 37, 60-62, 67, 69, 75, 85-88, 231, 233, 238, 244, 269-271, 281, 282,
      292] or books [49, 227, 293] that have focused on more selective aspects of the
      kinesin family, or have been aimed more generally at MT motor proteins. In line
      with the stated purpose of the Protein Profile series, annual updates of the
      review on the kinesins are planned for at least the next few years.

PMID- 8542444
TI  - Immunohistochemical localization of NAD glycohydrolase in human and rabbit
      tissues.
AB  - NAD glycohydrolase (NADase) is present in many organisms from bacteria to
      mammals. In any given organism, this enzyme is ubiquitous in many tissues.
      However, its precise localization and its physiological significance have not
      been defined. We have determined the distribution of NADase in normal human and
      rabbit tissues by immunoblotting and immunohistochemistry, using a polyclonal
      antibody raised in goats. Immunoblot analyses revealed that NADase was highly
      expressed in the heart, lung, stomach, and liver tissues of the rabbit. From
      immunohistochemical studies of NADase, high concentrations in both human and
      rabbit tissues were found in hepatocytes and sinusoidal lining cells, sinus
      histiocytes of the lymph node, spleen and thymus, glomerular capillary
      endothelial cells of the kidney, cardiac muscle, endothelium of blood vessels,
      and erythrocytes.

PMID- 8542445
TI  - Alkaline phosphatase reactivity in rabbit airway epithelium: a potentially useful
      marker for airway basal cells.
AB  - The purpose of this study was to investigate alkaline phosphatase (ALPase)
      reactivity in rabbit airway epithelial cells. Acetone-fixed, methyl benzoate and
      xylene-cleared (AMeX-treated) paraffin sections of trachea, bronchus, and lung
      tissue were stained by an azo dye coupling method for ALPase and examined by
      light microscopy. Electron histochemical staining was also performed in order to
      study the sensitivity and specificity of reactivity in each cell type. ALPase
      reactivity at the light microscopic level was observed exclusively in tracheo
      bronchial basal cells, and not in bronchiolar basal cells. By electron
      microscopy, ALPase reactivity was noted in 97.9% of basal cells in the trachea,
      97.0% of basal cells in the bronchus, and 94.5% of basal cells and 15.4% of Clara
      cells in the bronchiole. This was also true for dispersed tracheal epithelial
      cells. Reactivity was rarely observed in ciliated cells, non-goblet-type
      secretory cells, and undetermined cells. The reactivity was heat-labile,
      levamisole-sensitive, and of a non-specific type. These findings indicate that
      basal cells of rabbit trachea and bonchus have fairly high specificity for ALPase
      of a non-specific isozyme (92.2% and 95.6%, respectively). Therefore, ALPase is
      considered to be a useful marker for these cells.

PMID- 8542446
TI  - Bioluminescence in scale-worm photosomes: the photoprotein polynoidin is specific
      for the detection of superoxide radicals.
AB  - Photosomes are the characteristic organelles of the luminous epithelium in the
      elytral appendages of polynoid annelids. They are paracrystals of endoplasmic
      reticulum and emit a flash of bioluminescence in response to stimulation. The
      series of flashes in response to repetitive stimulation begins with a period of
      facilitation because the number of reacting photosomes increases in each
      photogenic cell. Reacting photosomes are coupled to the plasma membrane by dyad
      junctions which are established under stimulation and dedifferentiate in the
      resting system. The calcium influx of an action potential propagated through the
      conducting elytral epithelium triggers the luminous reaction. This reaction is
      based on a membrane photoprotein, polynoidin, which is specifically triggered by
      superoxide radicals. These oxy radicals result from the oxydation of riboflavin,
      which is present in a compartment of the photosomes. Polynoidin proved to be an
      interesting probe in the detection of superoxide radicals produced by activated
      white blood cells. Its potential applications are discussed.

PMID- 8542447
TI  - Identification of M-cells in the rabbit tonsil by vimentin immunohistochemistry
      and in vivo protein transport.
AB  - The rabbit palatine tonsil was studied by electron microscopy to determine
      whether M-cells similar to those of the Peyer's patches exist in the tonsil
      epithelium. A subpopulation of crypt epithelial cells was found with long,
      irregularly shaped microvilli, small cytoplasmic vesicles and engulfing
      intraepithelial lymphocytes and macrophages. Using ultrastructural
      immunohistochemistry, vimentin, the rabbit maker for intestinal and bronchial M
      cells, was detected in the cytoplasm of these cells, whereas no vimentin
      immunoreactivity was found in the remaining epithelial cells. The vimentin
      filaments surrounded the nucleus of the presumed M-cells and lay beneath the
      plasma membrane that surrounded intraepithelial lymphocytes. In vivo experiments
      using horseradish peroxidase as tracer revealed that this protein was endocytosed
      by the presumed M-cells and transported to the intercellular spaces between
      epithelial cells and lymphocytes. The results indicate that specialized
      epithelial cells exist in the tonsil which have morphological characteristics
      similar to those of intestinal M-cells, are in close contact to cells of the
      immune system, are positive for the rabbit M-cell marker vimentin, and are
      capable of antigen uptake and transcytosis. It is therefore concluded that M
      cells are present in the tonsil and probably play a role in the initiation of
      immune responses to orally delivered antigens.

PMID- 8542448
TI  - Light- and electron-microscopic immunocytochemical investigation of the
      subcommissural organ using a set of monoclonal antibodies against the bovine
      Reissner's fiber.
AB  - Ten monoclonal antibodies (Mabs) against glycoproteins of the bovine Reissner's
      fiber (RF) have been used in a structural and ultrastructural immunocytochemical
      investigation of the bovine subcommissural organ (SCO) and RF. The SCO of other
      vertebrate species has also been studied. For comparison, polyclonal antibodies
      against bovine RF (AFRU) were used. The SCO and RF of ox, pig and dogfish and the
      SCO of dog, rabbit, rat and frog were submitted to light-microscopic
      immunocytochemistry using AFRU and Mabs. Postembedding ultrastructural
      immunocytochemistry was applied to sections of bovine SCO using AFRU and Mabs.
      Bovine SCO consists of ependymal and hypendymal cell layers, the latter being
      arranged as cell strands across the posterior commissure, or as hypendymal
      rosette-like structures. All cytoplasmic regions of the ependymal and hypendymal
      cells were strongly stained with AFRU. Six Mabs showed the same staining pattern
      as AFRU, one Mab stained RF strongly and SCO weakly, two Mabs stained RF but not
      SCO, and, finally, one Mab (3B1) exclusively stained the apices of the ependymal
      and hypendymal cells. All Mabs recognized the SCO and RF of the pig. Two Mabs
      bound to the SCO of the dog. One Mab stained the SCO of the rabbit and another
      the SCO of the rat. The SCO of frog and dogfish were totally negative. Bovine SCO
      stained with AFRU, showed label in the rough endoplasmic reticulum (RER) and the
      secretory granules (SG) of the ependymal and hypendymal cells. The former, in the
      form of parallel cisternae, reticulum or concentric rings, was seen throughout
      all cytoplasmic regions. SG were abundant in the apical pole of the ependymal and
      hypendymal cells. Only one Mab showed a staining pattern similar to AFRU. Five
      Mabs showed strong reactions in the SG but weak labeling of the RER. Mab 3B1
      showed the label confined to the SG only. Our results suggest that: (i) in the
      bovine tissue, some epitopes are present in both precursor and processed
      materials, whereas others are characteristic of mature glycoproteins present in
      SG and the RF; (ii) the bovine SCO secretes at least two different compounds
      present in ependymal and hypendymal cells; (iii) both compounds coexist in the
      same secretory granule; (iv) there are conserved, class-specific, and species
      specific epitopes in the glycoproteins secreted by the SCO of vertebrates.

PMID- 8542449
TI  - Immunohistochemical correlation of human adrenal nerve fibres and thoracic dorsal
      root neurons with special reference to substance P.
AB  - Applying a double-labelling immunofluorescence technique, six types of substance
      P-containing nerve fibres were distinguished in the human adrenal gland according
      to the immunohistochemical colocalization of (I) calcitonin gene-related peptide
      (CGRP), (II) cholecystokinin, (III) nitric oxide synthase, (IV) dynorphin, (V)
      somatostatin, and (VI) vasoactive intestinal polypeptide. Fibre populations I to
      IV in their mediator content resembled the respective subpopulations of primary
      sensory neurons in human thoracic dorsal root ganglia, while populations V and VI
      revealed no correspondence with dorsal root neurochemical coding. Nerve fibres
      with the combination substance P/nitric oxide synthase occurred only in the
      adrenal cortex, whereas all other fibre types were present in both cortex and
      medulla. As revealed by immuno-electron microscopy, substance P-immunolabelled
      axon varicosities (a) exhibited synaptic contacts with medullary chromaffin cells
      or with neuronal dendrites, (b) were directly apposed to cortical steroid cells
      and (c) were separated from fenestrated capillaries only by the interstitial
      space. These findings provide immunochemical support for an assumed sensory
      innervation of the human adrenal gland, and additionally suggest participation of
      substance P in efferent autonomic pathways. Furthermore, the results are
      indicative for a differentiated involvement of substance P in the direct and
      indirect regulation of neuroneuronal and neuroendocrine interactions.

PMID- 8542451
TI  - BSACI Special Interest Group Report on Food Allergy and Intolerance. June 1992
      September 1993.

PMID- 8542450
TI  - Differences in distribution and synthesis of the functional opponents alpha 1
      proteinase inhibitor and neutrophil elastase in eukaryotic cells.
AB  - Alpha 1-proteinase inhibitor (alpha 1-Pi) is the main physiological inhibitor of
      neutrophil elastase, a serine protease that has been implicated in tissue
      degradation at inflammatory sites. We report here on an immunocytochemical study
      of various eukaryotic cells in order to show their content of alpha 1-Pi. The
      proteinase inhibitor is present in undifferentiated and differentiated HL-60 and
      U937 cells, in myeloblasts and neutrophils, and also in tissues such as liver,
      kidney, colon and eye where local inflammatory processes can take place.
      Labelling of HL-60, U937, neutrophils and HepG2 cells with [35S] methionine
      followed by immunoprecipitation of cell homogenates with an anti-alpha 1-Pi
      antibody revealed that these cells can synthesize alpha 1-Pi de novo, and secrete
      large amounts of the newly synthesized molecule into the medium. In contrast,
      neutrophil elastase is only present in white blood cells of myeloid and monocytic
      lineage but not in other tissues investigated which contain alpha 1-Pi. The
      results demonstrate the possibility of ubiquitous local synthesis of alpha 1-Pi
      ready to inhibit the elastase which is imported into the affected tissues during
      inflammatory processes by circulating cells of the haematopoietic system.

PMID- 8542452
TI  - Evidence for cell-mediated hypersensitivity as an important pathogenetic
      mechanism in food intolerance.

PMID- 8542453
TI  - The diagnosis of food intolerance.

PMID- 8542454
TI  - Food-allergic disease.

PMID- 8542455
TI  - Diagnostic criteria for gastrointestinal food allergy in childhood.

PMID- 8542456
TI  - Food and behaviour.

PMID- 8542457
TI  - Reactions to food additives.

PMID- 8542458
TI  - Food intolerance and asthma.

PMID- 8542459
TI  - IgE-mediated (and food-induced) intestinal disease.

PMID- 8542460
TI  - Oral sodium cromoglycate: its use in the management of food allergy.
AB  - In the management of food allergic conditions orally administered sodium
      cromoglycate can be used in a supportive role to an elimination diet. It can
      either be used in addition to a diet when this does not provide complete control
      of symptoms or to provide cover against short-term breaks in the diet.

PMID- 8542461
TI  - Dietary treatment of food allergy and intolerance.

PMID- 8542462
TI  - IgG and IgA antibodies to dietary antigens in food allergy and intolerance.

PMID- 8542463
TI  - Changes of bone mineral density in pregnant and postpartum women.
AB  - OBJECTIVE: To explore the effects of pregnancy and postpartal lactation on bone
      mineral density (BMD). METHODS: In this study, the BMD of 22 pregnant women in a
      longitudinal study, and of 75 pregnant and 111 puerperant women in a cross
      sectional study was estimated at the distal radius of the forearm by dual energy
      X-ray absorptiometry. BMD was measured on 8 separate occasions from the first
      trimester of pregnancy to 24 months' postpartum. RESULTS: In none of 22 pregnant
      women was there any noticeable change in BMD during pregnancy. Whereas no
      significant change in BMD occurred during the 12-month postpartum period in 11
      non-lactating women, 11 women who breastfed had a significant decrease in BMD at
      1, 3, and 6 months' postpartum, with all of them showing a further decrease in
      BMD at 12 months' postpartum. The BMD of the radius was significantly lower in
      the breast-feeders than in the formula-feeders at all postpartal times of
      evaluation except at 24 months' postpartum. CONCLUSION: It can be recommended
      that lactating women receive appropriate treatments for saving BMD during
      lactation.

PMID- 8542464
TI  - The value of Doppler study of the umbilical artery in predicting perinatal
      outcome in pre-eclamptic patients.
AB  - OBJECTIVE: To test the value of routine Doppler study of the umbilical artery to
      predict the perinatal outcome in pre-eclamptic patients. METHODS: Fetal wellbeing
      was assessed in 113 women with pre-eclampsia by weekly performed biophysical
      profile score (BPP) and Doppler study of the umbilical artery starting early in
      the third trimester till delivery. RESULTS: The last Doppler result before
      delivery was normal in 82 cases and abnormal in 31 cases. The group with abnormal
      Doppler had significantly higher blood pressure and serum uric acid level, and
      significantly lower platelet count than the group with normal Doppler. The
      incidence of IUGR, low Apgar score at 5 minutes, perinatal deaths and operative
      delivery for fetal distress was significantly higher in the group with abnormal
      Doppler. CONCLUSIONS: The abnormal Doppler result usually precedes the appearance
      of abnormal BPP. The abnormal Doppler result helps to identify the fetus at risk
      that needs further surveillance.

PMID- 8542465
TI  - Xanthogranulomatous oophoritis: an unusual complication of typhoid.

PMID- 8542466
TI  - Carcinoma of the uterine cervix presenting as superior vena cava syndrome: report
      of three cases and a review of literature.
AB  - We present three cases of superior vena cava syndrome secondary to carcinoma of
      the uterine cervix which manifested 2 to 7 years after the initial diagnosis and
      primary therapy. In two of these patients, tissue diagnosis could be obtained.
      Two patients expired within two months of presentation despite timely
      radiotherapy, and one case died after six months of diagnosis.

PMID- 8542467
TI  - Rapid chromosome analysis and prenatal diagnosis using fluid from the cystic
      hygroma, hydrothorax and isolated ascites: new source for chromosome analysis.
AB  - OBJECTIVE: To determine whether abnormally collected fetal body fluid could be
      used as alternative cell sources for cytogenetic assessment. METHOD: Using
      modified lymphocyte culture, the abnormal fetal body fluids obtained from the
      five fetal anomaly cases (3 cystic hygromas, 1 hydrothorax, and 1 isolated
      ascites) were analyzed in order to determine their karyotypes. RESULTS: Two cases
      showed 45, X and 46, XX/45, X and the other three showed a normal karyotype.
      CONCLUSION: The cytogenetic analysis from body fluid aspiration yields a rapid
      and accurate result within 96 hours. This method could be helpful when
      cordocentesis or placental biopsy is not feasible or when time requirement for
      amniotic fluid cell culture is burdensome to patient management.

PMID- 8542468
TI  - A case of ovarian serous adenocarcinoma suggestive of transformation to an AFP
      producing tumor during chemotherapy.
AB  - Ovarian serous adenocarcinoma with AFP production is very rare. A case involving
      a 66-year-old woman with an elevated serum AFP level without detectable hepatic
      involvement. AFP-positive cells were seen in the tumor at the second surgery.
      Fifty-seven percent of serum AFP from the patient bound Con A, whereas 43% did
      not. Similarly, 54% of the tumor fluid also bound Con A. These suggest that the
      serum AFP was similar to that of gastrointestinal tumors and yolk-sac tumors.

PMID- 8542469
TI  - Posthemorrhagic hydrocephalus in a fetus with severe tachycardia.
AB  - Although posthemorrhagic hydrocephalus has been observed in premature infants,
      few cases of its intrauterine occurrence in fetuses have been reported. We report
      a case of posthemorrhagic hydrocephalus in a fetus with severe tachycardia. This
      case indicates that its possible occurrence should be considered in a case of a
      preterm fetus with distress.

PMID- 8542470
TI  - Progression of vulvar intraepithelial neoplasia III to invasive carcinoma in a
      young woman.
AB  - This case documents the progression of untreated vulvar intraepithelial neoplasia
      to invasion in a young woman over a four and a half year period. Conflicting
      views with regards to the natural history of VIN II are discussed.

PMID- 8542471
TI  - Magnetic resonance imaging of autosomal recessive polycystic kidney disease in
      utero.
AB  - OBJECTIVE: To assess the efficacy of ultrasonography (USG) and magnetic resonance
      imaging (MRI) in diagnosing a particular urologic disease, autosomal recessive
      polycystic kidney disease (ARPKD). SUBJECT: A patient with a case of ARPKD, as
      diagnosed by USG and MRI. RESULT: USG revealed features typical of ARPKD; the
      kidneys were enlarged and echogenic, with a loss of normal renal architecture.
      MRI revealed anatomical features similar to those demonstrated by USG.
      Furthermore, MRI showed clearer delineation and tissue specificity of the
      affected kidneys. CONCLUSION: USG and MRI were useful in diagnosing ARPKD. MRI
      can serve as an adjunctive method for diagnosing certain fetal anomalies.

PMID- 8542472
TI  - Maternal and perinatal mortality/morbidity associated with cesarean section in
      Indonesia.
AB  - OBJECTIVES: To compare the frequencies of maternal mortality and perinatal
      mortality, and severe morbidity among cases of cesarean delivery. STUDY DESIGN: A
      cohort study, the outcome of major interest (cesarean section) being evaluated
      retrospectively and the cohort being hospital-based and actually covering a 10
      year period. SUBJECTS: Six hundred sixty-three cesarean deliveries out of a total
      of 7,128 births in the period 1981-1983 and 761 out of 8,534 in 1988-1990 were
      analyzed. STATISTICAL ANALYSIS: Chi-square statistical analysis and Linear
      regression analysis were used. RESULTS: The maternal mortality was 985.7/100,000
      live births and 757.5/100,000 live births in period I and II, respectively.
      Perinatal mortality in the two periods was 125.6 per 1,000 live births and 90.8
      per 1,000 live births, respectively. Although the cesarean birth rate did not
      increase, there was a decrease in maternal and perinatal mortality. The study
      demonstrated that although overall maternal mortality was high, the fatality rate
      in cesarean delivery was low: 4.5 and 2.6 per 1,000 cesarean sections in period I
      and II, respectively. CONCLUSIONS: Maternal mortality and perinatal mortality
      following cesarean delivery were more related to maternal illness rather than the
      surgery.

PMID- 8542473
TI  - Mid-second trimester organic acids in severe open neural tube defects.
AB  - OBJECTIVE: To investigate amnioic fluid organic concentrations at 16 weeks
      gestation from normal fetuses and those affected by severe neural tube defects.
      METHODS: Amniotic fluid collected from normal, anencephalic and severe open spina
      bifida fetuses was analysed for up to 24 organic acids by gas liquid
      chromatography. RESULTS: Significant increase in organic acids similar to those
      observed in defects of phenylalanine and tyrosine metabolism were identified when
      compared with the normal fetuses. Significant differences in organic acid
      concentrations were also identified within the two neural tube defect groups.
      CONCLUSION: A relationship between phenylalanine and tyrosine metabolism, closure
      rate of the neural tube and folate metabolism is proposed.

PMID- 8542474
TI  - Risk factors for Wolfe's dysplasia of mammograms in postmenopausal Turkish women.
AB  - OBJECTIVE: The aim was to ascertain whether menstrual, reproductive and hormonal
      risk factors for breast cancer are present in women with dysplastic mammographic
      patterns and to investigate possible trends towards breast cancer. METHOD: This
      prospective case-control study was designed in a university hospital. Thirty-two
      turkish postmenopausal women were evaluated for the associations between obesity,
      parity, age, age at menarche, age at menopause, total lactation period and
      dysplasic mammographic patterns. RESULTS: We found an increasing trend of
      dysplasia with increasing age at menarche. This association contradicts the well
      established one for breast cancer. The effects of parity and total lactation
      period on dysplasia were similar. Although nulliparity had some protective
      effects on dysplasia, relative risk (RR) increased to some extent with an
      increase in parity and lactation period. Later menopause and older age were
      associated with an increase risk of dysplasia, whereas an apparent protection was
      given by greater body mass index. CONCLUSION: Onset of the menopause increases
      the risk of dysplasia and the estrogenic milieu may have some role in the
      initiation and progression of dysplasia.

PMID- 8542475
TI  - Thyroid hormone in hyperemesis gravidarum.
AB  - OBJECTIVE: Several studies have suggested that nausea and vomiting in early
      pregnancy are related to the levels of thyroid hormones and human chorionic
      gonadotropin (hCG). To ascertain this relationship, we investigated 60 pregnant
      women (30 subjects each with morning sickness and hyperemesis gravidarum) and
      compared them with 30 control subjects (by enzyme immunoassay method). METHODS:
      Serum T3, T4 and TSH were determined in all the subjects while serum hCG was
      assayed in pregnant women only. Group comparison was done by applying Student's t
      test and the relationship between various parameters was evaluated by calculating
      coefficient of correlation, "r". RESULTS: Serum T4 and hCG levels were
      significantly increased in hyperemesis gravidarum while TSH demonstrated a
      significant decline in the same group. Correlation analysis showed a direct
      relationship between serum T4 and hCG and an inverse relationship between serum
      TSH and hCG in pregnancy with morning sickness. CONCLUSION: Our results are
      suggestive of the involvement of these variables in the pathogenesis of morning
      sickness and hyperemesis gravidarum not only because their levels were
      significantly altered but the extent of increase or decrease in their level
      correlated well with the severity of symptoms in the study subjects.

PMID- 8542476
TI  - A series of 1000 consecutive out-patient diagnostic hysteroscopies.
AB  - OBJECTIVE: To review the success of out-patient diagnostic hysteroscopy. METHOD:
      Retrospective review of 1000 consecutive out-patient hysteroscopies. RESULTS:
      Hysteroscopy was successfully performed in 96%. Cervical dilatation was required
      in 15.0% and local anaesthesia was administered in 31.4%; 77.3% of those
      requiring cervical dilatation received local anaesthesia. Intrauterine pathology
      was noted in 49.3%. The procedure failed in 40 (4%) patients for the following
      reasons: pain or anxiety in 23, cervical stenosis in 11, equipment failure in 4,
      and extreme uterine retroversion and inadvertent false cavity formation in one
      case each. CONCLUSION: Out-patient diagnostic hysteroscopy is a safe, well
      tolerated and successful investigation procedure in the majority of patients and
      should be the procedure of choice for suspected intrauterine pathology.

PMID- 8542477
TI  - A case of true hermaphroditism with androgen insensitivity.
AB  - A phenotypically normal woman with a 46, XY karyotype was found to have a testis,
      an ovotestis, bilateral rudimentary uteri, and bilateral fallopian tubes. The
      endocrinological and pathological aspects of these findings are discussed.

PMID- 8542478
TI  - Second and early third trimester atrial natriuretic peptide (ANP) levels in
      pregnancies subsequently complicated by hypertension.
AB  - OBJECTIVE: To explore the clinical utility of measuring atrial natriuretic
      peptide (ANP) in the second and early third trimesters of pregnancy in order to
      predict pregnancy induced hypertension (PIH). METHODS AND MATERIALS: The study
      was done in a University Teaching Hospital. A prospective study of 200 women in
      their first pregnancy was conducted. ANP was measured at 2 gestational windows,
      20-26 weeks and 30-34 weeks. This was correlated with pregnancy outcomes, in
      particular PIH. Student's t-test was used to compare ANP levels between women who
      developed PIH and those who did not. The receiver operator curve (ROC) was used
      to determine its clinical utility. RESULTS: ANP levels were lower at 20-26 weeks
      in women who subsequently developed PIH but there was no significant difference
      at 30-34 weeks between women who had normotensive pregnancies and those who later
      developed PIH. The character of the ROC would indicate that it is not useful for
      prediction. CONCLUSION: ANP levels in the second and early third trimesters has
      limited clinical utility for the prediction of PIH.

PMID- 8542479
TI  - Combination treatment with cisplatin and schizophyllan for 7,12
      dimethylbenz(a)anthracene-induced rat ovarian adenocarcinoma.
AB  - OBJECTIVE: Experimental chemotherapy was conducted to investigate the combined
      effect of Schizophyllan (SPG) and Cisplatin (CDDP). METHODS: Rats with 7,12
      dimethylbenz(a)anthracene (DMBA)-induced ovarian adenocarcinoma received SPG
      and/or CDDP, were observed for the anti-tumor effect of the drugs and were
      subjected to immunohistochemical study. RESULTS: 1) Tumor reduction was enhanced
      by the combined use of SPG and CDDP; 2) The survival rate of rats given SPG alone
      was significantly higher than that of the control rats, and treatment with SPG
      combined with CDDP tended to improve the survival rate; 3) Immunohistochemically,
      an infiltrative increase in cytotoxic T-lymphocytes (CTL) was induced, although
      the development of helper T-cells and macrophages was immunohistochemically weak
      at the tumor site. CONCLUSION: The administration of SPG enhanced the anti-tumor
      effect of CDDP.

PMID- 8542480
TI  - A new approach to methotrexate and lipiodol suspensions for ectopic pregnancy:
      preliminary in vitro and animal experiments.
AB  - OBJECTIVES: To measure and evaluate the in vitro release of MTX from suspensions
      of methotrexate (MTX) and lipiodol (LPD), and to investigate the MTX
      concentration and fertility rate using an animal model. METHODS: This study was
      divided into three components: a) An in vitro Release Study, b) Animal Study No.
      1 (concentration of tissue and plasma levels), and c) Animal Study No. 2
      (fertility rate after MTX suspension). RESULT: The releasing rate in vitro was
      more rapid with MTX-S (MTX dissolved in saline) than with either MTX-LPD (MTX
      dissolved in lipiodol) or MTX-LPD-PC (MTX suspended in lipiodol and
      phosphatidylcholin, i.e., MTX suspension). The tissue concentration tended to be
      higher with an MTX suspension than with MTX-S. There was no significant
      difference in the fertility rate or the nidation index among the 3 groups (Groups
      1, 2, and 3). CONCLUSION: The injection of an MTX suspension is useful for
      increasing the tissue concentration and maintaining the long-term effectiveness
      of MTX, and this technique might offer a new approach in the treatment of ectopic
      pregnancy (EP) or in second-line therapy for persistent EP.

PMID- 8542481
TI  - More or less compliant?

PMID- 8542482
TI  - All our students are honor students.

PMID- 8542483
TI  - Right lung ventilation during thoracotomy.

PMID- 8542484
TI  - Association of out-of-hospital criteria with need for hospital admission.
AB  - OBJECTIVE: To validate high-risk historical and physiologic out-of-hospital
      criteria as predictors of the need for hospitalization following ED evaluation.
      METHODS: Consecutive patients entered into the Suffolk County advanced life
      support system were enrolled. Previously proposed historical and physiologic
      "high-risk" criteria for hospitalization were prospectively collected. Criteria
      were associated with the need for hospital admission following ED evaluation.
      RESULTS: 1,238 patients were enrolled; 391 were released from an ED after
      transport. Most patients (843/1,238; 68%) were admitted to a hospital; and four
      died in the ED. Factors associated with an increased likelihood of admission or
      death among the transported patients were: bradycardia (90% admitted, p < 0.02);
      hypotension (80%, p < 0.03); hypertension (89%, p < 0.03); and age > 55 years
      (81%, p < 0.0001). Unresponsiveness and other abnormal vital signs were not
      associated with admission on univariate analysis. Logistic regression analysis
      identified two other factors associated with admission or death: tachycardia (72%
      admitted, p < 0.01) and head injury (78% admitted, p < 0.001). CONCLUSIONS:
      Abnormal pulse or blood pressure, head injury, and age > 55 years are associated
      with patients' requiring hospital admission after accessing the emergency medical
      services system. These criteria may aid the design of out-of-hospital refusal-of
      care policies.

PMID- 8542486
TI  - Lung compliance following cardiac arrest.
AB  - OBJECTIVE: To determine lung compliance in patients who had out-of-hospital
      cardiac arrests. METHODS: A prospective, observational study of patients
      suffering nontraumatic cardiopulmonary arrest and requiring CPR at one university
      hospital ED. Following termination of resuscitation efforts, lung compliance was
      measured. Measurements were made while inflating the lung from 250 mL to 2,000 mL
      (in 250-mL increments) using a calibrated supersyringe. Airway flow and pressure
      were measured at the endotracheal tube with a pneumotachograph and a pressure
      transducer. Flow and pressure signals were recorded by a respiratory monitor and
      used to construct pressure-volume curves for calculation of lung compliance.
      RESULTS: The 25 cardiac arrest patients (17 men, eight women) had a mean (+/- SD)
      age of 65 +/- 7 years. Mean lung compliance was 0.051 +/- 0.011 L/cm H2O. Lung
      compliance was smaller at low lung volumes, suggesting the presence of alveolar
      collapse. Compliance values from 500 mL to 1,500 mL were similar. Compliance also
      diminished with increasing duration of CPR. CONCLUSIONS: One previous publication
      suggested that lung compliance following resuscitation is 0.022 L/cm H2O. The
      results of this study, using the accepted standard measurements of static lung
      compliance, suggest that true compliance is twice this value. This finding has
      important ramifications for future research on ventilation during resuscitation
      and current ventilation standards.

PMID- 8542485
TI  - Ultrasonographic examination by emergency physicians of patients at risk for
      ectopic pregnancy.
AB  - OBJECTIVE: To evaluate a diagnostic protocol that includes the early use of
      endovaginal sonography (EVS) by emergency physicians of patients at risk for
      ectopic pregnancy. METHODS: During this prospective study, pregnant patients > or
      = 18 years old and at risk for ectopic pregnancy were assessed. Emergency
      physicians who had completed a training program performed EVS on a convenience
      sample of eligible women. Clinical disposition was based on predetermined
      clinical, laboratory, and ultrasonographic criteria. The EVS examinations were
      reviewed on video by a gynecologist whose interpretation was correlated with the
      emergency physician EVS readings and with the final clinical diagnoses.
      Quantitative serum beta-human chorionic gonadotropin (beta hCG) levels were
      determined for patients who had no definite intrauterine pregnancy (IUP) on EVS.
      RESULTS: Of 152 patients studied during a 12-month period, four were lost to
      follow-up. Emergency physician ultrasonographic diagnoses included: definite IUP,
      87/148 (59%); probable abnormal IUP, 17/148 (11%); definite ectopic pregnancy,
      3/148 (2%); and no definite IUP, 41/148 (28%). The gynecologist agreed with 93%
      of the initial interpretations. Twelve of 16 patients who had the final diagnosis
      of ectopic pregnancy were admitted from the ED with this diagnosis. The
      ultrasonographic diagnosis of the other four was no definite IUP, and no mass or
      free fluid. For the latter four patients, the presenting serum beta hCG level was
      < 2,000 mIU/mL (First International Reference Preparation). They were diagnosed
      as having ectopic pregnancy after serial outpatient EVS and beta hCG
      measurements. CONCLUSIONS: The application of EVS to emergency practice appears
      promising. Emergency physicians trained in its use and who apply this diagnostic
      tool in conjunction with a defined protocol can stratify the risk of patients who
      have the potential for ectopic pregnancy.

PMID- 8542487
TI  - Combination fentanyl and diazepam for pediatric conscious sedation.
AB  - OBJECTIVES: To evaluate the safety and to describe the use of combination IV
      diazepam and fentanyl in the pediatric emergency department (PED) as outpatient
      conscious sedation (CS) for orthopedic procedures. METHODS: A retrospective chart
      review of a standardized protocol for CS administered to 133 consecutive patients
      requiring CS for outpatient orthopedic procedures. The patients were continuously
      monitored for heart rate, respiratory rate, and arterial O2 saturation (Sao2) by
      pulse oximetry. The study was conducted at a large urban PED and regional
      referral center. RESULTS: A total of 133 children (mean age 8.5 years) received
      138 orthopedic procedures. Mean (+/- SD) total diazepam dose was 0.12 +/- 0.05
      mg/kg; mean total fentanyl dose was 3.18 +/- 1.04 micrograms/kg. Mean time
      intervals were 4.6 minutes from initial drug administration to start of
      procedure, 15.5 minutes to end of procedure, and 56 minutes to meeting criteria
      for release home. Complications included Sao2 < 90% for 15 patients (11%, 95% CI
      6.4-17.4%), vomiting for one (0.7%, 95% CI 0.1-4.2%), and severe pruritus for one
      (0.7%, 95% CI 0.1-4.2%). An episode of Sao2 < 90% was associated with a higher
      initial mean fentanyl dose (2.60 vs 1.95 micrograms/kg; p = 0.0005), but was not
      associated with a higher initial mean diazepam dose (p = 0.28). Parenteral opioid
      use for pain management prior to CS was not associated with an increased risk for
      Sao2 < 90% (p = 0.42). Heart rate, respiratory rate, and blood pressure were
      stable during the observational period. No patient required naloxone, flumazenil,
      artificial airway control, or admission to the hospital. CONCLUSIONS: At the
      doses given in the study, the use of combination diazepam and fentanyl for
      outpatient CS of PED patients during orthopedic procedures was not associated
      with serious complications. A higher initial fentanyl dose was associated with
      episodes of Sao2 < 90%. Therefore, an initial dose of < or = 2.0 micrograms/kg
      fentanyl titrated to effect is recommended.

PMID- 8542488
TI  - Infiltration pain and local anesthetic effects of buffered vs plain 1%
      diphenhydramine.
AB  - OBJECTIVE: To compare the levels of infiltration pain and local anesthetic
      effects of plain and buffered 1% diphenhydramine. METHODS: A prospective,
      randomized, double-blind, paired study was performed using 30 adult volunteers.
      Intradermal injections (0.5 mL) of plain and buffered 1% diphenhydramine were
      made in the subjects' forearms, one in the left and the other in the right. The
      pain of infiltration was recorded on a previously validated 10-cm visual analog
      scale (VAS). The volunteers also were asked which injection was less painful.
      Sequential measurements of the diameter of anesthesia to pinprick were made at 1,
      2, 5, 10, 15, 20, 25, and 30 minutes. The VAS scores and anesthetic diameters
      were compared for plain and buffered diphenhydramine using a paired Wilcoxon rank
      sum test. RESULTS: There was no statistically significant difference between
      buffered diphenhydramine and plain diphenhydramine for pain of injection (23.5 +/
      19.2 mm vs 28.2 +/- 18.7 mm, p = 0.24). Repeated-measures analysis of variance
      for anesthetic diameters demonstrated no significant difference between buffered
      diphenhydramine and plain diphenhydramine (p = 0.87). At no single measurement
      period were the anesthetic diameters different. CONCLUSIONS: In a study with a
      sample size large enough to detect an 11-mm difference in VAS scores (power =
      80%), no difference was found in pain of infiltration and anesthetic effects when
      plain 1% diphenhydramine was compared with buffered 1% diphenhydramine. Buffering
      of diphenhydramine does not appear to result in a clinically significant
      reduction in the pain of infiltration.

PMID- 8542489
TI  - Right lung ventilation in a porcine open-chest shock model.
AB  - OBJECTIVE: To determine the effect of selective right lung ventilation on gas
      exchange and hemodynamics when compared with bilateral lung ventilation in a
      porcine open-chest shock model. METHODS: A randomized, controlled laboratory
      investigation was performed using a static hemorrhagic shock model in 12 adult
      swine undergoing thoracotomy. The animals were subjected to a fixed 40%
      circulating blood volume hemorrhage over 20 minutes. Each animal was then
      assigned to either a tracheal (control) or a right mainstem (experimental)
      intubation group. Minute ventilation was held constant in both groups and tidal
      volumes were decreased by 33% in the right mainstem intubation group. Following
      intubation and left lateral thoracotomy, another 20% fixed-volume hemorrhage was
      instituted simultaneously with IV crystalloid and whole blood resuscitation for
      both groups over 30 minutes. Heart rate, blood pressure, and arterial blood gases
      were measured at 5-minute intervals. RESULTS: There was no significant difference
      between the control and experimental groups for any of the measured variables,
      including mean arterial pressure, pH, partial arterial pressure of CO2 (PaCO2),
      and PaO2, over time. All animals survived the study protocol. CONCLUSION:
      Selective right lung ventilation has no detrimental effect on gas exchange or
      hemodynamics when compared with standard bilateral lung ventilation in a porcine
      open-chest shock model.

PMID- 8542490
TI  - Continuous noninvasive determination of pulsus paradoxus: a pilot study.
AB  - OBJECTIVE: To evaluate two methods of continuous, noninvasive monitoring of
      pulsus paradoxus (PP). METHODS: A single-subject, nonblind assessment was
      conducted of the ability of noninvasive monitoring techniques to measure
      experimentally induced PP. Variable degrees of PP were induced in a healthy adult
      breathing through a one-way valve to which a series of external airway
      resistances were added. Intra-arterial pressure (IAP), finger arterial blood
      pressure (FINAP), pulse oximeter pulse waveform, and chest wall motion were
      continuously recorded. For each resistance, PP was calculated from the IAP
      (PPIAP) and the FINAP (PPFINAP) recordings. PP was measured manually (PPmanual)
      in the opposite arm. The percentage pulse waveform decrease on inspiration
      (%PWDpleth) was derived from the oximeter pulse waveform. These measurements were
      compared with the PPIAP. Bias was assessed as the mean difference between PP
      measures. RESULTS: PPFINAP was highly correlated with PPIAP (r = 0.96; 95% CI
      0.93 to 0.98; p < 0.0001). There was a weak correlation between PPmanual and
      PPIAP (r = 0.27; 95% CI -0.05 to 0.55; p = 0.0963). The %PWDpleth correlated with
      PPIAP (r = 0.59, 95% CI 0.32 to 0.78; p = 0.0002). Bias was -1.515 +/- 5.6 mm Hg
      between PPIAP and PPFINAP; and -4.508 +/- 23.4 mm Hg between PPIAP and PPmanual.
      CONCLUSION: An accurate and continuous PP can be measured noninvasively using a
      FINAP monitor. This method has much better agreement with IAP measurements than
      do manual measurements. The qualitative information provided by the oximeter
      pulse waveform is less accurate than that provided by the FINAP monitor, but is a
      potentially useful screening tool for detection of significant PP.

PMID- 8542491
TI  - Evaluation of capnography in nonintubated emergency department patients with
      respiratory distress.
AB  - OBJECTIVE: To evaluate the ability of noninvasive capnographic measurement of end
      tidal CO2 tension (PetCO2) to predict arterial CO2 tension (PaCO2) in
      nonintubated ED patients with respiratory distress. METHODS: A prospective,
      nonblind study was performed in a level I trauma center/community teaching
      hospital ED. Participants included all nonintubated adult patients with
      respiratory distress requiring measurement of arterial blood gases (ABGs); 29
      patients were enrolled. PetCO2 was measured with a capnography monitor, using
      both baseline tidal volumes and forced expiratory volumes. The bias between
      PetCO2 values and simultaneous measurements of PaCO2 by ABG was assessed.
      RESULTS: PetCO2, measured with forced expiration, and PaCO2 agreed well, with
      bias (i.e., average difference) = 0.44 +/- 0.52 kPa (3.3 +/- 3.9 torr). PetCO2
      measured with the tidal volume breath produced an unacceptably high bias of 0.82
      +/- 0.70 kPa (6.1 +/- 5.2 torr). Levels of agreement between PaCO2 were similar
      for smokers and nonsmokers and for men and women. The arterial-end-tidal CO2
      tension (Pa-etCO2) difference was not related to PaCO2. Pa-etCO2 correlated with
      age (r = 0.473; p = 0.01), and was significantly higher in patients with
      pulmonary disease (1.32 +/- 0.56 kPa; 9.9 +/- 4.2 torr) than it was in those
      without pulmonary disease (0.46 +/- 0.55 kPa; 3.5 +/- 4.1 torr; p < 0.001).
      CONCLUSIONS: Noninvasive PetCO2 monitoring may adequately predict PaCO2 in
      nonintubated ED patients with respiratory distress who are able to produce a
      forced expiration. PetCO2 is less accurate for PaCO2 with tidal volume breathing
      and in patients with pulmonary disease.

PMID- 8542492
TI  - Observation of emergency medicine residents at the bedside: how often does it
      happen?
AB  - OBJECTIVE: To determine how often trainees in emergency medicine (EM) are
      observed while performing a history, a physical examination, or specific
      procedures. METHODS: The 26 members of the National Consensus Group on Clinical
      Skills in Emergency Medicine affiliated with an EM residency program were asked
      to circulate a survey to their residents during February and March 1994. Twenty
      one programs participated, surveying a total of 514 residents. The residents were
      asked how many times they had been observed by an attending physician while they
      performed a history, a physical examination, endotracheal intubation, or central
      vein catheterization during training. The residents also were asked about
      observation of specific components of the physical examination, such as the
      heart, lung, and genitourinary systems. RESULTS: Three hundred nineteen residents
      (62%) responded to the survey. Thirteen percent of the residents reported that
      they had never been observed taking a history during training. During their PGY1
      training, 19% of the residents reported that they had never been observed taking
      a history, 42% had been observed one to three times, 25% had been observed four
      to 12 times, and 13% had been observed > 12 times. Six percent of the residents
      reported that they had never been observed doing a physical examination during
      training. During their PGY1 training, 10% of the residents had never been
      observed performing a physical examination, 38% had been observed one to three
      times, 34% had been observed four to 12 times, and 18% had been observed > 12
      times. CONCLUSIONS: Many residents report that they are infrequently observed
      performing histories and physical examinations during their EM training, with a
      significant number of residents reporting that they were never observed
      performing basic bedside clinical skills. More direct observation with trained
      faculty observers may provide an opportunity for better evaluation and
      remediation of bedside clinical skills.

PMID- 8542493
TI  - Directing an emergency medicine residency: the problems and their potential
      solutions.
AB  - OBJECTIVE: To characterize the problems facing emergency medicine residency
      directors (EMRDs), to describe potential solutions, and to associate perceptions
      with anticipated duration in the position of EMRD. METHODS: A confidential
      questionnaire was mailed to the EMRDs at all Accreditation Council for Graduate
      Medical Education-approved programs. The survey included a problem and solution
      list constructed by a panel of EMRDs. The respondents were asked to rate problems
      using a Likert-like scale and were asked to indicate which of the listed
      solutions they had used and had found useful, or thought would be useful.
      Associations of these features and demographic variables with the intention to
      leave the position of EMRD within 5 years were sought. RESULTS: Eighty-seven of
      93 EMRDs (93.5%) completed the survey. Their mean age was 40 years; 50% had been
      EMRDs for < 3 years. Most of the EMRDs (62%) had an associate EMRD, and 77% had
      at least one secretary. The EMRDs worked a median of 220 hours per month. Major
      problems included: insufficient time for the job (57%), career interfering with
      family needs (44%), and lack of adequate faculty help (38%). The most frequently
      cited and useful solutions included: attending education courses, self-reading on
      education and management techniques, and discussing problems with and seeking
      advice from others. Most (68%) of the EMRDs anticipated continuing as program
      director for < or = 5 years. Neither age, gender, previous amount of time in the
      position, number of hours worked, nor nature of the problems faced on the job was
      a significant predictor of which of the EMRDs anticipated leaving. CONCLUSIONS:
      Half the responding EMRDs were < 40 years of age, half had been EMRDs for < or =
      3 years, and 68% anticipated continuing in their position for < or = 5 years.
      Major frustrations included lack of knowledge and time. Family and career
      conflicts were frequent. These problems are similar to those of program directors
      in other specialties. Some recommendations are made to assist EMRDs.

PMID- 8542494
TI  - Right hand and arm rash Mycobacterium marinum infection.

PMID- 8542495
TI  - New models for emergency and ambulatory care at academic health centers--Part II:
      Texas.

PMID- 8542496
TI  - Sudden infant death syndrome--Part I: General features.

PMID- 8542498
TI  - Managed care system for central Virginia: its potential impact on academic
      emergency medicine.

PMID- 8542497
TI  - Clinicopathological conference: young man with syncope.

PMID- 8542499
TI  - Paramedic accuracy in estimated time of arrival: significance in the managed care
      environment.

PMID- 8542500
TI  - Pneumoperitoneum associated with manual ventilation using a bag-valve device.

PMID- 8542501
TI  - New entities, concepts, and questions in childhood tumor pathology.
AB  - There are major differences between tumors in children and adults, viz. the
      incidence of tumor types, the predisposition of certain organs and tissues (e.g.
      sympathetic nervous tissue, kidney, and soft tissues) to develop tumors, problems
      related to tumor classification, and the biologic behavior of childhood
      malignancies, which are usually characterized by high rates of proliferation
      activity. A large number of new entities, especially in soft tissue tumors, have
      been published over the past years, including nodular mesothelial hyperplasia,
      which is a tumor-like lesion derived from peritoneal macrophages; infantile
      myofibromatosis, which can mimic leiomyosarcoma; intermediate grade
      fibrohistiocytic tumors, like dermatofibrosarcoma protuberans-related giant-cell
      fibroblastoma, plexiform fibrohistiocytic tumor and angiomatoid malignant fibrous
      histiocytoma displaying evidence of myogeneous differentiation; finally, the high
      grade intraabdominal desmoplastic small cell tumor. With modern methods we can
      gain better insights into the biology of tumors. For example, tumors of the
      Ewing's sarcoma family have in common a characteristic t(11; 22) chromosomal
      translocation, the Ewing's sarcoma (EWS) (22q12) gene rearrangement, and the MIC2
      gene. The EWS gene rearrangement is not restricted to tumors of the Ewing's
      sarcoma family (classic Ewing's sarcoma and malignant peripheral neuroectodermal
      tumor), however, but occurs in malignant melanoma of the soft tissue and in
      intraabdominal desmoplastic small cell tumor. Rhabdomyosarcomas (RMS) can be
      divided into two basic types with different prognoses: embryonal RMS, including
      botryoid and spindle-cell variants, and alveolar RMS, including the solid
      variant. The prognosis of alveolar RMS is poorer than that of classic embryonal
      RMS, mainly due to early tumor dissemination in alveolar RMS. The prognosis of
      neuroblastoma is mainly based on chromosomal and molecular biologic findings.
      Structural chromosome 1 abnormalities, double minute chromosomes, homogeneously
      staining regions, N-myc amplifications, and DNA diploidy are indications for an
      unfavorable outcome. Despite progress in childhood solid tumor pathology, many
      questions remain open, including those relating to basic chromosomal defects in
      germ cell tumors and the obscure nature of tumor heterogeneity.

PMID- 8542502
TI  - Inflammatory, preneoplastic, and neoplastic changes of the gastric mucosa.
      Examinations by the AgNORT-technique.
AB  - The gastric surface epithelium of 101 antrum biopsies was examined by the AgNOR
      technique. The material included normal mucosa, Helicobacter pylori gastritis,
      gastric ulcer, intestinal metaplasia type I and type III, dysplasia grades I-III
      and carcinoma. Starting from normal mucosa, a continuous increase in the number
      of AgNORs could be observed. At the same time, the size of the individual AgNOR
      dots decreased. The entire AgNOR area per cell and the AgNOR quotient were
      ascertained. Groups of significant differences were found and could be clearly
      defined by cluster analysis. Intestinal metaplasia type I corresponded to
      inflammatory changes, whereas intestinal metaplasia type III was related to
      dysplastic lesions.

PMID- 8542503
TI  - Kupffer cells in multiple organ failure--their activation as revealed by
      immunohistochemistry for lysozyme, alpha 1-antichymotrypsin, and lectins.
AB  - It has been recently suggested that multiple organ failure (MOF) is caused by
      activation of inflammatory cells and subsequent release soluble factors from
      these cells. However, morphologic data to support this hypothesis is lacking.
      Thus, the present study was conducted to evaluate the activation of Kupffer cells
      in multiple organ failure by applying immunohistochemical techniques to formalin
      fixed, paraffin-embedded autopsy materials. Eleven liver samples of multiple
      organ failure were stained for lysozyme, alpha 1-antichymotrypsin, and by
      lectins, such as ConA, RCA-I, WGA and PNA. Normal livers and diseased livers of
      miscellaneous origins were also stained and compared. In normal livers, Kupffer
      cells were generally negative or weakly positive for lysozyme, alpha 1
      antichymotrypsin, ConA, RCA-I, and PNA, while they were positive for WGA. In
      multiple organ failure, by contrast, Kupffer cells showed stronger staining for
      alpha 1-antichymotrypsin, lysozyme, ConA, RCA-I, WGA, and PNA, indicating
      activation of Kupffer cells. Increased reaction to WGA and RCA-I was also
      observed in diseased livers of miscellaneous origins. These results are in
      agreement with the current hypothesis that activation of Kupfer cells is involved
      in the pathogenesis of MOF. Our findings also indicate, however, that activation
      of Kupffer cells is not a phenomenon unique to MOF.

PMID- 8542504
TI  - Nuclear morphometry of renal cell carcinomas.
AB  - In this study, the correlation between different morphometric nuclear parameters
      and grading of renal cell carcinoma was investigated. Nuclear area, the standard
      deviation of the nuclear area and the form factor (FF) were assessed using a
      computer assisted image analyzer system. A statistically significant difference
      between G2 and G3 carcinomas could be confirmed for the nuclear area and the
      standard deviation of the nuclear area, with the significance level being lower
      for the latter parameter. Normal tubular epithelia and G1 carcinomas showed no
      significant difference in the nuclear area and the standard deviation of the
      nuclear area. In contrast, the form factor discriminated between normal tubular
      epithelium and G1 carcinomas, whereas no difference of the FF between G2 and G3
      carcinomas was found. Reclassification of the subjectively assessed tumor grading
      was performed by means of linear discriminant analysis using all possible
      combinations of the different nuclear parameters. This procedure disclosed an
      increasing rate of correctly reclassified grading with rising number of
      parameters applied. We conclude that the isolated assessment of nuclear area does
      not suffice for the correct morphometric tumor grading, and that further
      parameters describing the nuclear shape have to be applied additionally in
      studies concerning morphometric nuclear grading.

PMID- 8542505
TI  - Neuropathologic findings after organ transplantation. An autopsy study.
AB  - Since 1972 organ transplantations of kidney, bone marrow, liver, heart and lung
      have been performed at the University Hospital of Essen, Germany. Out of 2535
      transplantations until September 1993, autopsies were performed in 157 patients
      In 25 patients (15.9%) neuropathologic findings (n = 26) were found. In 97
      autopsies after bone marrow transplantation, 9 patients (9.3%) exhibited a severe
      neuropathologic alteration. In six patients (6/9; 66.6%), necrotisizing
      toxoplasmose encephalitis was found. Other cases showed a septic-metastatic
      mycotic encephalitis with crypto-coccus neoformans and candida albicans (n = 2)
      and leucemia infiltrates (n = 1). Massive cerebral hemorrhage was the most
      frequent neuropathologic finding after liver (4/8) and kidney transplantation
      (3/6). In addition liver-transplanted patients exhibited septic-metastatic
      encephalitis (3/8) and embolic brain infarct (1/8) as well as cerebral metastases
      (2/6) and primary malignant cerebral lymphoma in kidney transplantation (1/6).
      CNS findings in five autopsies after heart-lung-transplantation were diverse.
      They comprised intracerebral hemorrhage, intravasal lymphoma and septic
      metastatic encephalitis, respectively. In summary, neuropathologic autopsy
      findings after organ transplantation are diverse and preferentially comprise
      infections, cerebral hemorrhages, and malignant lymphomas. After bone marrow
      transplantation, the most frequent neuropathologic autopsy finding was
      toxoplasmose encephalitis and massive cerebral hemorrhages after liver and kidney
      transplantations.

PMID- 8542506
TI  - The antibody to plasminogen activator inhibitor-1 suppresses pulmonary metastases
      of human fibrosarcoma in athymic mice.
AB  - We studied the effects of the plasminogen activator inhibitor-1 (PAI-1), the
      urokinase-type plasminogen activator (uPA) and their antibodies on hematogeneous
      pulmonary metastases formation of human fibrosarcoma in athymic mice. We used a
      human fibrosarcoma cell line (HT-1 080) with low metastatic potential, and a
      subpopulation of HT-1 080 (HT-1 080-P4) with high metastatic potential which was
      selected by repeating injections into the tail veins of athymic mice. We examined
      the effects of these drugs on pulmonary metastases formation according to
      Wexler's method and the number of tumor cell emboli in the lung subsequent to an
      injection of radio-labeled tumor cells. Pulmonary metastases formation from HT-1
      080 was not affected by any of the tested drugs. Pulmonary metastases from HT-1
      080-P4 increased with uPA and anti-uPA antibody injections. PAI-1 slightly
      increased pulmonary metastases from HT-1 080-P4, and the anti-PAI-1 antibody
      decreased it (60.9 + 27.7% of control, p < 0.05). While none of the drugs altered
      the number of HT-1 080 cells in the lung at 24, 48 and 72 hours after the
      injection, PAI-1 increased the number of HT-1 080-P4 cells in the lung, whereas
      uPA and PAI-1 decreased it. The result that these drugs did not affect the
      metastatic potential of HT-1 080 but only that of HT-1 080-P4, indicates that
      fibrinolysis plays an important role in hematogenous pulmonary metastases
      formation of tumor cells with high metastatic potential. The effects of uPA
      suggest that uPA facilitates pulmonary metastasis formation probably due to an
      increase in the invasive ability of tumor cells. The effects of PAI-1 and its
      antibody of HT-1 080-P4 cells suggest that PAI-1 may facilitate tumor cell
      lodgement in vessels and the anti-PAI-1 antibody could be able to suppress
      pulmonary metastases of tumor cells with high metastatic potential by inhibition
      of tumor cell lodgement in vessels.

PMID- 8542507
TI  - Parachordoma--a clinicopathologic, immunohistochemical, electron microscopic,
      flow cytometric, and cytogenetic study.
AB  - A case of parachordoma in a 45-year-old female was described. Histologically, the
      recurrent lesion, in comparison with the primary tumor, demonstrated an increased
      cellular atypia and mitotic rate. The tumor cells expressed EMA, vimentin, S 100
      protein, and also a trace desmin content was present. Electron microscopic study
      provided no characteristic features of the tumor type studied. Flow cytometric
      evaluation of the DNA demonstrated a diploid histogram with the relatively high S
      phase. Cytogenetic analysis revealed normal karyotype, but a deviation from the
      diploid state in the form of aneuploid metaphases with non-clonal structural
      chromosomal aberrations was observed.

PMID- 8542508
TI  - Virilizing stromal Leydig cell tumor (Leydig cell-containing thecoma) of the
      ovary in pregnancy. A case report with extensive immunohistochemical
      investigation of the tumor cells.
AB  - The rare case of a stromal Leydig cell tumor of the ovary occurring in a 21-year
      old woman who developed signs of virilization during pregnancy is reported. Serum
      androgen levels were markedly elevated. At cesarean section, a slightly
      hypotrophic, but otherwise normal, female infant was delivered and a tumor of the
      right ovary measuring 12 cm in maximum diameter was resected. Histologic
      examination revealed a sex cord-stromal tumor consisting of spindle-shaped,
      thecomatous cells and a large number of loosely scattered clusters of large
      polygonal cells with abundant eosinophilic cytoplasm. Both types of tumor cells
      were strongly immunoreactive for vimentin, but exhibited no proliferative
      activity and no overexpression of p53 protein. A few of the polygonal cells
      contained typical crystalloids of Reinke. Cellular atypia was not a prominent
      feature, and a diagnosis of benign stromal Leydig cell tumor was established. As
      expected, 20 months after diagnosis the patient exhibits no signs of recurrence
      or dissemination. To the best of our knowledge this is only the second case of a
      stromal Leydig cell tumor occurring in pregnancy to be described.

PMID- 8542509
TI  - Hepatoid adenocarcinoma of the stomach: a case report.
AB  - A case of primarily inoperable hepatoid adenocarcinoma of the stomach is
      reported, which, after chemotherapy with farmorubicin, 5-fluorouracil and
      leucovorin, showed an impressive regression resulting in an improvement of the
      overall condition of the patient and a decrease of the serum AFP level from
      initially 79.120 ng/ml to 3.728 ng/ml. In a second operation the tumor was
      removed and intraoperative radiation therapy was applied to the head of the
      pancreas and intraabdominal lymph nodes. Furthermore, we discuss the main
      pathologic features of this rare tumor entity and give a short review of the
      literature.

PMID- 8542510
TI  - Synchronous multifocal bone sarcomas--a case report and molecular pathologic
      investigation.
AB  - A case of a 54-year-old woman is described who developed synchronously two
      malignant bone tumors: a dedifferentiated chondrosarcoma in the olecranon and a
      malignant fibrous histiocytoma (MFH) in the lower tibia. The anaplastic part of
      the dedifferentiated chondrosarcoma revealed an MFH-like pattern. Myogenous
      differentiations were not observed in the anaplastic sarcoma cells. The MFH in
      the tibia showed a storiform-pleomorphic pattern. Single tumor cells showed
      positivity for M-actin and desmin pointing to myogenous differentiation. DNA
      cytophotometry of the dedifferentiated chondrosarcoma showed an aneuploid stem
      cell line. The MFH in the tibia did not reveal aneuploid stem cells. Staining for
      p53 protein was negative in both tumors. SSCP analysis and sequencing of the p53
      gene in both tumors revealed in the dedifferentiated chondrosarcoma a mutation in
      exon-8 with the transversion from G to T in codon 294 resulting in a substitution
      of a stop codon for GLU. The mutation was not observed in the MFH. From these
      immunohistologic, DNA-cytometric and molecular biologic investigations, we
      consider it probable that the tumor in the lower tibia is a second highly
      malignant bone tumor and not the metastasis of the dedifferentiated portion of
      the dedifferentiated chondrosarcoma in the olecranon.

PMID- 8542511
TI  - Intravenous leiomyomatosis of the uterus.
AB  - A case of intravenous leiomyomatosis of the uterus and 4 subperitoneal, pelvic
      leiomyomas without any connection to the uterus is demonstrated. The
      intravascular position of the tumors is proved by immunohistochemistry with
      positive reaction of antibodies against von Willebrand Factor. This rare growth
      pattern of benign leiomyoma of the uterus often shows extrauterine extension by
      intravascular growth within venous channels, sometimes causing cardiovascular
      complications. This tumor should not be confused with malignant neoplasia.

PMID- 8542512
TI  - The Montreal Heart Attack Readjustment Trial.

PMID- 8542513
TI  - Ability of the Caltrac accelerometer to assess daily physical activity levels.
AB  - PURPOSE: The purpose of this study was to determine the ability of the Caltrac
      accelerometer to assess habitual daily physical activity levels. METHODS: The
      ability of the Caltrac accelerometer to assess 24-hour physical activity (PA)
      levels was studied in 28 men and 50 women, age 20 to 59 years, with varying
      levels of self-reported PA. Twelve days of Caltrac readings obtained over 1
      year's duration were compared to simultaneously recorded 48-hour PA records.
      Additionally, 28 days of Caltrac readings obtained over 1 year's duration were
      compared to mean values of the following validation measures assessed repeatedly
      over a 1-year period: a 4-week version of the Minnesota Leisure Time Physical
      Activity Questionnaire (FWH); VO2peak; and percent body fat. RESULTS: The Caltrac
      measurements of movement (in MET minutes per day-1) were significantly associated
      with the following: PA record indices of total (r = .51) and heavy (r = .34) and
      PA; FWH indices of total (r = .30), heavy R = .36) and moderate (r = .23) PA;,
      and VO2peak (r = .24). However, the Caltrac measurements of caloric PA record and
      FWH indices of PA, although there were directly associated with percent body fat
      (r = .50) and inversely associated with VO2peak (r = -.26). CONCLUSIONS: Caltrac
      measurements of movement exhibited a moderate associated with several criterion
      measures related to habitual PA, whereas Caltrac measurements of total energy
      expenditure, were not reflective of varying levels of PA.

PMID- 8542514
TI  - Failure of hyperoxic gas to alter the arterial lactate anaerobic threshold.
AB  - PURPOSE: Oxygen-enriched gases enable patients and healthy individuals to
      exercise submaximally with reduced lactate concentration, lower minute
      ventilation (VE), and less subjective stress compared to normoxia. These findings
      suggest that hyperoxia may raise the lactate accumulation threshold, also known
      as the anaerobic threshold (AT). METHODS: This study measured the anaerobic
      threshold by gas exchange (Gx-AT) and arterial lactate (Lac-AT) methods in
      normoxia (FIO2 = 0.209) and the Lac-AT in hyperoxia (FIO2 = 0.40). Eight healthy
      males (age = 30.6 +/- 3.5 years; weight = 73.4 +/- 5.2 kg; VO2max = 41.3 +/- 6.6
      mL/kg/min) worked incrementally (25 Watts [W] x 2 minutes) on a cycle ergometer
      with the legs on three occasions: once in normoxia, twice in hyperoxia. The
      latter situation enabled a reliability analysis of hyperoxic anaerobic threshold
      by arterial lactate methods that yielded a correlation coefficient (r) of 0.94
      and nonsignificant paired t-ratio. Gas exchange and arterial lactate methods of
      detecting the anaerobic threshold in normoxia yielded nearly identical VO2 (21.8
      +/- 5.4 mL/kg/min vs 21.5 +/- 5.5 mL/kg/min) with an r of 0.98. RESULTS: Contrary
      to the study's hypothesis, the normoxic Lac-AT (134.4 +/- 35.2 W), expressed in
      power output at which the lactate threshold occurred, was not significantly
      different with hyperoxic gas (128.1 +/- 32.7 W). Furthermore, arterial lactate
      concentration at the breakpoint in normoxia (1.74 +/- 0.50 mmol.l-1) was not
      significantly affected by hyperoxia (1.68 +/- 1.03 mmol.l-1) nor was it different
      between the two hyperoxic tests. No significant differences in VE, HR, or CO2
      ventilation equivalent at Lac-AT were found between the two FIO2 conditions.
      CONCLUSIONS: The elevation of estimated PaO2 to 200 mm Hg does not alter the Lac
      AT, compared to the normoxic condition, nor does it affect the arterial lactate
      concentration at its systematic break point in incremental cycling. Lac-AT is a
      reliable measurement and it can be estimated accurately using the VE/VO2 in
      conjunction with VE/VCO2.

PMID- 8542515
TI  - Physical fitness, physical activity, and fatness in relation to blood pressure
      and lipids in preadolescent children. Results from the FRESH Study.
AB  - PURPOSE: The cross-sectional gender patterns of fitness, activity, and fatness
      were examined in relation to blood pressure and lipids in 9- to 10-year-old
      children. METHODS: Subjects were fourth graders (26 boys and 27 girls)
      participating in FRESH, a school-based heart health program. The main variables
      of interest were fitness determined on a treadmill, habitual physical activity by
      self-report, fatness by skinfolds and body mass index, blood pressure, and
      lipoprotein lipids. RESULTS: Physical fitness and activity were higher in boys,
      whereas fatness and triglycerides were higher in girls. Systolic blood pressure
      correlated positively with fatness in girls, and there was a trend for this
      relationship in boys. In boys, total LDL cholesterol correlated positively with
      fatness and negatively with fitness. By multivariate analysis, fitness was the
      primary correlate of total and LDL cholesterol. In girls, fitness correlated
      positively with total and LDL cholesterol. This finding was opposite in boys.
      Fatness correlated negatively with HDL cholesterol in boys. CONCLUSION: Boys are
      more fit and active and less fat than girls. Fatness in young children already
      shows a relationship with heart disease risk factors. In boys, fitness shows a
      favorable relation to lipids. These data along with other studies suggest that
      more consistent relationships among fitness, activity, fatness, blood pressure,
      and lipids are likely to emerge as children approach adolescence. The findings
      also underscore the complexity of defining these relationships in young children.

PMID- 8542516
TI  - The effects of a 9-week program of aerobic and upper body exercise on the maximal
      voluntary ventilation of chronic obstructive pulmonary disease patients.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of a 9-week
      exercise program that emphasized aerobic and upper body strength on the maximal
      voluntary ventilation (MVV) of patients with chronic obstructive pulmonary
      disease (COPD). An experimental and control group totaling 40 patients with a
      diagnosis of COPD was studied. METHODS: Experimental group subjects were given a
      pre- and post-MVV breathing test, a Patient's Attitude Toward Health (PATH)
      questionnaire, a knowledge of disease questionnaire and a 6-minute walk test. Pre
      and post-MVV breathing tests were performed on the control group. Dependent t
      test and analysis of covariance were utilized to evaluate the results. RESULTS:
      Significant differences were found between the pre-test and post-test within the
      experimental group on MVV results, program attitudes toward health (PATH scores),
      knowledge level about their disease state after the rehabilitation program, and 6
      minute walk distance. There were no significant differences found in the MVV
      results between the pre-test and post-test for the control group. There was a
      significant difference when comparing the control group MVV results to the MVV
      results of the exercise group. CONCLUSIONS: These findings indicate that
      pulmonary rehabilitation programs can help patients realize improved lung
      function, improved emotional states, increased knowledge about their disease
      states, and an increased cardiovascular fitness level. The results of this study
      suggest a regimen that can improve the quality of life for patients with chronic
      lung disease.

PMID- 8542517
TI  - Stair climbing elicits a lower cardiovascular demand than walking in claudication
      patients.
AB  - PURPOSE: Peripheral arterial disease patients limited by claudication pain
      frequently have concomitant-cardiovascular problems during exercise, such as
      hypertension and myocardial ischemia. Thus, for testing and rehabilitation
      purposes, exercise which elicits lower heart rate and blood pressure at a given
      metabolic intensity would be preferred over a more demanding task. The purpose of
      this study was to compare the cardiovascular responses of claudication patients
      during walking and stair climbing at a similar level of oxygen uptake. METHODS:
      Ten patients limited by claudication pain performed treadmill walking and stair
      climbing tests. RESULTS: Oxygen uptake was similar (P > .05) during walking and
      stair climbing (13.7 vs. 13.5 mL/kg/min, respectively). The times to onset and to
      maximal claudication pain, as well as the peripheral hemodynamic measurements of
      ankle systolic pressure, ankle-to-brachial systolic pressure index, and foot
      transcutaneous oxygen tension were also similar between the two tests (P > .05).
      However, heart rate, systolic pressure, diastolic pressure, mean arterial
      pressure, and rate-pressure product values were lower during and following stair
      climbing than compared to walking (P < .05). CONCLUSION: Stair climbing may offer
      an advantage over treadmill walking for claudication patients because similar
      metabolic, claudication, and peripheral hemodynamic measurements are obtained
      with concomitantly less demand placed on the cardiovascular system. The stair
      climbing test was well tolerated and safely performed by each patient.

PMID- 8542518
TI  - Gender differences in perceptions of quality of life in cardiac rehabilitation
      patients.
AB  - PURPOSE: Coronary artery disease remains the leading cause of death in the United
      States for both men and women. Patients actively participating in cardiac
      rehabilitation programs obtain both physiological and psychological benefits that
      have a significant positive impact on their quality of life. However, women have
      been underrepresented in research on cardiovascular disease and on the
      rehabilitation process. The purpose of this study was to determine if there were
      gender differences in perceptions of quality of life in cardiac rehabilitation
      patients. METHODS: Convenience sampling with blocking for age was used in the
      selection of 87 women and 87 men from 6 cardiac rehabilitation programs in
      Louisiana. RESULTS: Using the Ferrans and Powers Quality of Life Index--Cardiac
      Version, the t-test for independent samples revealed significant gender
      differences. Men's mean scores were significantly higher than women's mean scores
      on overall quality of life scores and each of the four subscales. The men's
      scores were significantly higher as follows: overall (P = .0026), health and
      functioning (P = .004), socioeconomic (P = .012), psychological/spiritual (P =
      .026), and family (P = .001). An additional finding indicated that men had a
      significantly higher number of invasive cardiac procedures (P = .0026).
      CONCLUSION: From the results of this study, individualized and gender-specific
      plans of care need to be directed at clients with cardiovascular disease.

PMID- 8542519
TI  - Arguments in favor of screening for diabetes in cardiac rehabilitation.

PMID- 8542520
TI  - Clinical competency guidelines for pulmonary rehabilitation professionals.
      American Association of Cardiovascular and Pulmonary Rehabilitation Position
      Statement.

PMID- 8542521
TI  - The Mediterranean diet and cardiovascular disease.

PMID- 8542522
TI  - Beta-blockers and their effects on protein metabolism and resting energy
      expenditure.
AB  - In summary, beta-adrenergic receptor blocking medications have numerous metabolic
      side effects. Recent evidence indicates that this class of drug acutely decreases
      whole-body metabolic rate and increases protein oxidation in the resting human.
      The result of this metabolic perturbation may be a deleterious change in body
      composition and perhaps a creeping increase in body weight, if no subsequent
      alterations are made in food consumption or activity patterns. Research indicates
      that long-term treatment with beta-blockade may increase body fat and decrease
      the fat-free tissue content of the organism. Exercise is known to favorably
      affect body composition by decreasing percent body fat, while increasing the fat
      free body tissue. Beginning a regular, moderate exercise program may help
      ameliorate these deleterious nutritional side effects of long-term beta-blocker
      therapy. Additionally, the recommendation to engage in a moderate exercise
      program is further indicated because of the underlying cardiovascular
      pathophysiology that originally required long-term beta-adrenergic treatment.

PMID- 8542523
TI  - Cardiac rehabilitation based on group light exercise and discussion. An
      Australian hospital model.
AB  - Patients with cardiac disease potentially have many physical, psychological, and
      social problems. With adequate rehabilitation, most patients can return to
      enjoyable, productive lives. If rehabilitation programs can be provided at
      relatively low cost, they can be introduced more widely. It is obviously
      important that low-cost programs should include most of the effective components
      of more sophisticated programs. The program presented here, based on group light
      exercise and discussion, is effective and inexpensive. Therefore, it provides a
      potential model for group cardiac rehabilitation in situations where cost
      containment is an important consideration.

PMID- 8542524
TI  - Exercise intensity prescription in cardiovascular disease. Theoretical basis for
      anaerobic threshold determination.

PMID- 8542525
TI  - Tri-State Regional Pulmonary Rehabilitation Survey. Program characteristics and
      practices.
AB  - PURPOSE: This report summarizes the pulmonary rehabilitation characteristics
      found in the 1991 survey of programs in the Pennsylvania, New Jersey, and
      Delaware region. METHODS: A listing of 111 potential Tri-state regional programs
      with pulmonary rehabilitation was compiled. A 34-item questionnaire was
      developed. Using multiple mailings and phone-call follow-up, 59 programs of 100
      the active programs in the region returned the questionnaires. Programs that were
      providing services to patients with pulmonary disease were compared to those
      focusing on patients with cardiac and/or pulmonary disease. RESULTS: A third of
      all programs (31%) used combined cardiopulmonary services. Pulmonary-only
      programs averaged 1.7 hours per day, and cardiopulmonary programs averaged 1.1
      hours per day (P < .01). Both types of programs averaged 2.4 days per week.
      Average duration of pulmonary-only programs was 8.7 weeks, and duration of
      cardiopulmonary programs was 10.6 weeks (P < .05). Most programs (85%) required
      referral from the patients' primary physician. Many programs (64%) reported that
      local physicians other than the program's medical director referred a majority of
      the patients. Almost all programs (92%) performed exercise testing before
      initiating pulmonary rehabilitation. Post-rehabilitation discharge planning
      seemed to be based in many programs on performance measures taken during the
      final rehabilitation sessions or from a final 6- or 12-minute walk. Educational
      sessions were provided by 95% of the programs. Maintenance sessions were not
      offered by 39% of the programs. Seventy-three percent of the pulmonary-only
      programs and 44% of the cardiopulmonary programs offered support groups (P <
      .05). The pulmonary-only program coordinator's specialty was mostly respiratory
      therapy (70%), whereas in cardiopulmonary programs, coordinators tended to be
      nurses (39%) or from other nonrespiratory specialties (28%). No respiratory staff
      were used by 38% of the cardiopulmonary programs. CONCLUSIONS: The type of
      rehabilitation program, either pulmonary-only or cardiopulmonary, appears to
      influence many program characteristics (e.g., hours per day, weeks in duration,
      coordinator's specialty, and staffing).

PMID- 8542526
TI  - Time course of recovery during cardiac rehabilitation.
AB  - PURPOSE: Exercise-based rehabilitation programs improve effort tolerance in
      patients with cardiovascular disease. Little is known regarding the time course
      of recovery of objective and subjective indices of exercise tolerance. METHODS:
      Twenty-six patients were studied at 0, 4, 8, and 12 weeks following early entry
      into rehabilitation following acute myocardial infarction (AMI), coronary artery
      bypass graft surgery (CABGS), or valve surgery. Exercise tolerance was assessed
      objectively by percent predicted cycle power output (%PO), and subjectively by a
      self-efficacy questionnaire for ambulatory (ASE) and muscular (MSE) items and by
      a disease-specific, health-related, quality-of-life questionnaire (HRQL).
      RESULTS: With the exception of percent predicted cycle power output, all exercise
      tolerance measures improved throughout the rehabilitation program. Extrapolation
      of recovery curves suggest that recovery to 85% predicted can be achieved in 10,
      11, 18, and 21 weeks for a disease-specific, health-related, quality-of-life
      questionnaire, self-efficacy questionnaire for ambulatory items, muscular items,
      and power output, respectively. CONCLUSIONS: The data demonstrate that evaluation
      of both objective and subjective indices of exercise tolerance may be important
      in documenting outcomes of participation in structured rehabilitation programs.
      The time course of recovery of objective and subjective indices of exercise
      tolerance may not be highly correlated.

PMID- 8542527
TI  - Oxygen uptake and cardiac output during progressive and constant load work in
      patients after acute myocardial infarction.
AB  - PURPOSE: Simultaneously measured oxygen uptake (VO2) and Doppler echocardiography
      could verify if an alteration in the VO2 response to progressive and constant
      load work is due to reduced cardiac output. METHODS: The study group consisted of
      nine patients after acute myocardial infarction (MI), five age-matched healthy
      subjects (HE), and five young well-trained subjects (WT). Each subject performed
      a progressive exercise test and two bouts of constant load work at power outputs
      equated to 10% below (W1) and 10% above (W2) their ventilatory thresholds. VO2
      and cardiac output were measured continuously and simultaneously during the
      tests. RESULTS: VO2 was significantly reduced for the MI group during the initial
      stages of the progressive exercise test (P < .02) and remained lower throughout
      the entire test. During the first 60 seconds of constant load work (W2), VO2 was
      lower for MI (P < .05). At steady state exercise during W2, cardiac output was
      significantly less for MI (P < .05). VO2 for the MI group was more reliant on
      cardiac output during lower power outputs and differences in the arterial and
      venous O2 content (a-VO2 difference) during greater power outputs. CONCLUSIONS:
      Cardiac rehabilitation programs must be aware of this delayed VO2 and cardiac
      output response when setting training workloads or selecting the magnitude of the
      workload increments during progressive exercise tests.

PMID- 8542528
TI  - Differences in quality of life among male and female cardiac rehabilitation
      participants.
AB  - PURPOSE: This study examined possible sex differences in quality of life measured
      by the Sickness Impact Profile (SIP) among cardiac rehabilitation participants.
      METHODS: Forty-five men (62.6 +/- 10.4 years) and 58 women (65.7 +/- 11.1 years)
      matched on time in a program, completed the Sickness Impact Profile. Exercise
      testing data and medical history were collected from medical records. RESULTS:
      Women reported significantly greater dysfunction on the total (7.01 vs 4.32),
      psychosocial (5.86 vs 2.48), home management (12.37 vs 16.69), and emotional
      behavior (7.32 vs 1.22) categories (P < .05). Women also had significantly
      greater (P < .05) incidence of widowhood, migraine/chronic headache, and
      arthritis than men. Men had significantly higher (P < .05) functional capacity
      (8.4 vs 6.9 metabolic equivalents [METS]). Covarying Sickness Impact Profile
      scores for functional capacity eliminated significant differences except in the
      emotional and psychosocial categories. Subjects with high grade chest pain,
      chronic low back pain, and migraine/chronic headache reported greater
      dysfunctional Sickness Impact Profile scores (P < .05). CONCLUSIONS: Women
      participating in cardiac rehabilitation reported poorer quality of life than men,
      particularly in the areas of psychosocial functioning and emotional behavior that
      were not dependent on functional capacity. Women's poorer quality of life may be
      related to a higher incidence of related diseases and their greater frequency of
      widowhood. The poorer quality of life of the women in categories of total SIP
      score and home management were related to their lower functional capacity.

PMID- 8542529
TI  - Exercise guidelines for patients with high blood pressure: an update.

PMID- 8542530
TI  - Value of gas exchange analysis in heart disease.

PMID- 8542531
TI  - The role of lipid management by diet and exercise in the progression,
      stabilization, and regression of coronary artery atherosclerosis.

PMID- 8542532
TI  - Exercise training frequency in early post-infarction cardiac rehabilitation.
      Influence on aerobic conditioning.
AB  - PURPOSE: The convalescent period after myocardial infarction (MI) has been
      associated with a "spontaneous" improvement in functional aerobic capacity that
      may be because of normal recovery processes unrelated to formal exercise
      training. The purpose of this study was to determine whether the frequency of
      formal training sessions is an important variable affecting the magnitude of
      improvement in cardiorespiratory fitness during phase II cardiac rehabilitation.
      METHODS: The effect of exercise training frequency on cardiorespiratory fitness
      was evaluated during a 5-week early (phase II) cardiac rehabilitation program in
      50 low-risk, male patients recovering from acute MI. Baseline graded treadmill
      tests to fatigue endpoints, with direct measurement of maximal oxygen uptake
      (VO2max), were administered 4 weeks after MI. The subjects were then randomly
      assigned to either a control group (n = 12) and restricted to "very light"
      physical activity (requiring < 50% of VO2max) at home, or to one of three
      training groups which, in addition to very light home activity, performed
      moderately intense (approximately 70% of VO2max) aerobic exercise for 30 to 35
      minutes either once per week (n = 13), twice per week (n = 13), or three times
      per week (n = 12) in the hospital-based phase II program. The four groups were
      similar in age, clinical status, and use of beta- and calcium channel blockers.
      RESULTS: Submaximal and maximal cardiorespiratory responses were initially
      similar in all four groups. Each of the four groups demonstrated significant (P <
      .05) increases in maximal treadmill duration at follow-up. However, VO2max
      increased significantly only in the three training groups. The spontaneous
      improvement in treadmill duration in the control group, in the absence of formal
      exercise training, may simply reflect recovery from the acute cardiac event.
      Those training two and three sessions per week also showed significant,
      comparable decreases in submaximal exercise heart rate and rate-pressure product
      and similar increases in maximal treadmill duration and VO2max. CONCLUSIONS:
      Results suggest that two exercise sessions per week is as effective as three per
      week for cardiorespiratory conditioning in the early weeks of phase II cardiac
      rehabilitation.

PMID- 8542533
TI  - A comparison of outpatient cardiac and pulmonary rehabilitation patients.
AB  - PURPOSE: Although cardiac and pulmonary rehabilitation are frequently considered
      together, differences in the two populations have not been evaluated adequately.
      METHODS: This study compared patients who were referred to outpatient cardiac and
      pulmonary rehabilitation over a 1-year period at the authors' institution. Fifty
      five cardiac rehabilitation patients (CR) and 47 pulmonary rehabilitation
      patients (PR) were studied with respect to age, gender, weight, smoking history,
      functional status, employment status, numbers and types of diagnoses and
      medications, and number of recent hospitalizations and hospital days. RESULTS:
      Cardiac rehabilitation patients were approximately 7 years younger, smoked less,
      were somewhat heavier, had a markedly better functional status, and were more
      likely employed than their counterparts in pulmonary rehabilitation. In addition,
      this group had fewer diagnoses and used fewer medications than PR patients. The
      number of hospitalizations and hospital days in the year preceding
      rehabilitation, however, were greater in CR patients than in PR patients.
      CONCLUSIONS: CR patients and PR patients are quite distinct with respect to
      demographics, functional status, comorbidity, and hospital resource consumption.

PMID- 8542534
TI  - Injuries during the one repetition maximum assessment in the elderly.
AB  - PURPOSE: A decrease in strength, and its associated loss of functional ability is
      common among the elderly. Although resistance training can reverse this decline,
      associated injuries with frequently used strength assessments may present a
      greater risk. METHODS: To evaluate the injuries associated with maximal strength
      evaluations, 83 relatively healthy elderly subjects (40 men and 43 women, 65.8 +/
      6.2 years) with and without prior weight training experience performed 1
      repetition maximum testing (1 RM) involving 5 different exercises: chest press,
      leg extension, abdominal curl, arm curl, and seated calf raise. Subjects were
      separated into three groups depending on weight training experience, Group 1 had
      no weight training experience (n = 32), Group 2 had < 6 months of training (n =
      24), and Group 3 had > 6 months of training (n = 27). Injury assessment was made
      30 minutes, 2 days, and 7 days posttesting. RESULTS: Two Group 1 subjects
      sustained an injury (2.4% of total subjects, 8% of Group 1). Eighty-one subjects
      safely completed the 1 RM assessment without injury (97.6% of total). Forty-eight
      of the 83 subjects complained of muscle soreness after testing (58% of total).
      This complaint alone was not sufficient to be categorized as an injury.
      CONCLUSIONS: These results indicate that 1 RM testing is an acceptable tool in
      strength evaluations in the elderly. Additional precautions may be needed in
      inexperienced, elderly individuals to prevent injury.

PMID- 8542535
TI  - Kinetics of the transplanted heart. Implications for the choice of field-test
      exercise protocol.
AB  - PURPOSE: The transplanted heart shows a slow increase (on transient) of both
      heart rate (HR) and oxygen consumption (VO2) at the beginning of exercise. The
      hypothesis used in this study was that this would lead to unacceptably large
      systematic errors when field predictions of maximal oxygen intake (VO2max) were
      derived from cycle ergometer tests with a steep ramp function. METHODS: The
      subjects (27 patients who had received orthotopic heart transplants 6 months
      previously, and 45 age-matched control subjects) each performed a rapid
      progressive cycle ergometer test (increments of 16.7 Watts [W] per minute to
      subjective exhaustion) and a "steady-state" test (two 6-minute stages at one
      third and two thirds of peak power output). Time constants for HR and VO2 were
      determined by fitting single exponent equations to the "steady-state" data and
      noting the time for the difference from the plateau value to reach 36.8% of its
      initial value. Heart rate and VO2 also were compared between rapid progressive
      and "steady-state" tests at one third and two thirds of peak power output.
      RESULTS: At one third of peak power output (46 W in patients, 73 W in control
      subjects), the respective time constants (mean +/- SE [standard error]) were 60.4
      +/- 6.4 and 40.5 +/- 3.0 seconds for VO2 (P < .01), and 130.0 +/- 14.3 and 67.9
      +/- 10.0 seconds for HR (P < .001). At two thirds of peak power, the
      corresponding values were 49.2 +/- 5.5 and 34.7 +/- 2.7 seconds for VO2 (P <
      .05), and 147.9 +/- 13.0 and 122.2 +/- 4.8 seconds for HR (P < .10). Comparing
      rapid progressive and "steady-state" readings, the control subjects showed
      identical values for HR and VO2 at one third of peak power, but at two thirds,
      the rapid progressive test HR lagged behind the "steady-state" value by 8 +/- 3
      beats per minute. The cardiac transplant patients showed a larger HR lag in the
      rapid progressive tests (109 +/- 12 vs 117 +/- 10 beats per minute, P < .05; 125
      +/- 14 vs 141 +/- 14 beats per minute, P < .005). Oxygen consumption also tended
      to lag slightly at two thirds of peak power (118 +/- 76 mL/min, not significant).
      CONCLUSIONS: The rapid progressive test protocol yields acceptable field
      estimates of aerobic power in normal individuals, but the slow acceleration of HR
      after cardiac transplantation leads to unacceptably large errors if the HR from a
      rapid progressive test protocol is used to predict maximal oxygen intake (VO2max)
      in such patients.

PMID- 8542536
TI  - Influence of microvascular architecture on oxygen exchange in skeletal muscle.
AB  - The normal function of skeletal muscle requires that a continuous supply of
      oxygen be provided by the cardiovascular system. This article reviews the
      development of our understanding of the role of microvascular architecture on the
      oxygen transport system, with emphasis on direct microcirculatory observations
      and mathematical modeling dating from the work of August Krogh to present
      studies. The contributions of the various elements of the vascular network (i.e.,
      arterioles, capillaries, and venules) and microvascular hemodynamics to oxygen
      exchange are discussed. Oxygen moves through the microvascular network by
      convection, almost all of it being reversibly bound to the hemoglobin within red
      blood cells. Thus, the flow properties and distribution of the red cells within
      the network can play a significant role in oxygen transport. Because the walls of
      all the vessels in the microcirculation appear to be permeable to oxygen, it
      continuously diffuses between the blood and the interstitium, the direction
      depending on the oxygen partial pressure difference. Because of the high
      permeability of the vascular wall to oxygen, the complex spatial relationships
      among the various microvessels lead to correspondingly complex diffusive
      interactions among them. The proximity of capillaries, arterioles, and venules,
      along with the anastomotic connections and tortuosity of capillaries, provides
      the "complex spatial relationships" that lead to diffusive interactions between
      neighboring capillaries, between capillaries and nearby arterioles and venules,
      and between paired arterioles and venules. Although there are a number of
      outstanding problems regarding our understanding of oxygen transport at the
      microcirculatory level, the most interesting and significant of these has to do
      with the adjustments that are made in the transition from the resting state to
      that of sustained aerobic exercise.

PMID- 8542537
TI  - The influence of flow and hematocrit on the laser Doppler flux signal from the
      surface of the perfused pig liver.
AB  - OBJECTIVE: We tested the hypothesis that the measurement volume of the laser
      Doppler flowmeter (LDF) is too small to provide reliable quantitative estimates
      of total liver blood flow of large mammals, such as the pig. METHODS: In a
      perfused pig liver, the influence of changing (i) hepatic arterial (HA) and
      portal venous flows individually (n = 9), (ii) HA flow at fixed portal venous
      flow (50%, 70%, and 100% expected total liver blood flow), and (iii) hematocrit
      (0-30%) at fixed total liver blood flow on LDF flux was tested (n = 8). RESULTS:
      Linearity of LDF with hepatic arterial flow and portal venous flow was confirmed;
      however, the slope of the regression lines was higher for hepatic artery [1.92 +/
      0.60 (SD)] than portal vein perfused livers (0.66 +/- 0.34; P < 0.001). With
      portal venous flow at 50% and 70% total liver blood flow, changing hepatic
      arterial flow produced linear LDF versus flow responses, but at 100% total liver
      blood flow, linearity was achieved in only 6/9 livers. The coefficient of
      variation for the slopes of regression lines was always > 30%. At constant total
      liver blood flow (100 ml/min per 100 g), LDF response decreased linearly by a
      factor of about 2 on changing the hematocrit from 30% to 5% and markedly fell as
      the hematocrit was further decreased to zero. CONCLUSIONS: These results suggest
      that (i) the LDF flux signal from the liver surface provides a poor measure of
      hepatic microcirculatory blood flow during changes in total liver blood flow as
      the LDF responds with about three times greater sensitivity to changes in hepatic
      arterial than in portal venous flow, and (ii) when hematocrit is falling, LDF may
      underestimate hepatic perfusion to a significant extent. In addition, due to high
      measurement variability, the LDF flux signal cannot be quantified in absolute
      perfusion units.

PMID- 8542538
TI  - Estimation of in vivo pulmonary microvascular and interstitial geometry using
      digital image analysis.
AB  - OBJECTIVE: To determine microvascular diameter and perivascular interstitium
      thickness at the lung surface in the in situ, in vivo lung. METHODS: Microscopic
      images of the lung surface collected through a "pleural window" by a videocamera
      were digitized with a monochrome frame grabber (512 x 512 pixels, 8 bits per
      pixels) to be computer analyzed by image processing techniques. RESULTS: We found
      that the maxima in the distribution of the standard deviations of gray levels in
      adjacent neighbors 7 x 7 pixels wide identify the edges between the microvessel
      lumen and the surrounding perivascular interstitium. Furthermore, the maxima in
      the distribution of the standard deviation of the standard deviations of gray
      levels identify the edges between the perivascular interstitium and the lung
      tissue. CONCLUSIONS: This technique can be applied to microvessels ranging in
      diameter from 30 microns to 200 microns and perivascular interstitial thickness
      of the order of 10-150 microns. Our approach allows for the definition of
      microvascular geometry even for noisy images and represents an improvement
      compared to other edge detection methods. The proposed analytical procedure may
      provide a useful tool to study lung fluid balance and microvascular reactivity in
      the in situ lung in the normal state and in response to a variety of functional
      conditions.

PMID- 8542539
TI  - A circumferential stress-growth rule predicts arcade arteriole formation in a
      network model.
AB  - OBJECTIVE: To test the hypothesis that terminal arteriolar remodeling that is
      stimulated by elevated levels of circumferential wall stress (sigma theta) will
      proceed in a network pattern that gives rise to new arcade arterioles. METHODS: A
      network model of two interconnected skeletal muscle arterio-capillary-venous
      units that incorporated diameter- and hematocrit-dependent blood viscosity was
      constructed. After computing the control values for wall shear stresses (tau ij)
      and sigma theta ij, a stimulus was provided by dilating the arterioles and
      raising input pressure. Wall shear stresses and sigma theta ij were then
      recomputed. The diameters of transverse arteriolar segments with sigma theta ij
      greater than a sigma theta threshold were increased by an amount that was
      dependent on the original diameter and the difference between sigma theta ij and
      the sigma theta threshold. Capillaries with an intraluminal pressure greater than
      a specified threshold were converted to terminal arterioles. Separate simulations
      in which remodeling was stimulated by elevated levels of tau ij were also
      performed for comparison. RESULTS: Arterialization patterns from simulations of
      sigma theta ij stimulated arteriolar remodeling were representative of those seen
      in vivo with arterialization of back-connection capillaries leading to arcade
      arteriole formation. Simulations based on similar rules for tau ij yielded
      arterio-venous shunts, which are rarely seen in vivo, but no arcade arterioles.
      CONCLUSION: The simulations presented here are consistent with the hypothesis
      that arteriolar remodeling is stimulated by increased levels of circumferential
      wall stress and that new arcade arteriole formation is a consequence of terminal
      arteriolar growth.

PMID- 8542540
TI  - Nitric oxide mediates C5a-induced vasodilation in the small intestine.
AB  - OBJECTIVE: This study was designed to investigate the microvascular responses of
      the small intestine to complement C5a and to define the role of nitric oxide in
      the C5a-induced response. METHODS: Male Sprague-Dawley rats were anesthetized
      with pentobarbital, and a loop of small intestine was exteriorized and suffused
      with Krebs solution. The diameters of large and small arterioles of the small
      intestinal wall were measured with in vivo videomicroscopy following the
      application of experimental mediators. Four 1-hr C5a dose-response trials were
      performed (10(-14) M, 10(-12) M, 10(-10) M, and 10(-8) M). Then, we completed
      acetylcholine dose-response curves with and without N omega-nitro-L-arginine (N
      Arg) to document the adequacy of nitric oxide synthase inhibition. The
      microvascular response to the topical application of C5a (10(-12) M) was recorded
      in the presence of 2 x 10(-4) M N-Arg. Additionally, experiments of C5a-induced
      response with N-Arg were repeated in the presence of L-arginine (L-Arg; the
      precursor of nitric oxide synthesis) or with systemic administration of
      superoxide dismutase (SOD). RESULTS: (1) C5a induces a dose-dependent
      vasodilation in the small intestine, and the maximal vasodilation occurs in A3
      arterioles at C5a concentration of 10(-12) M; (2) N-Arg inhibits the Ach-induced
      vasodilation in the rat small intestine; and (3) L-Arg or SOD partially reverses
      the inhibitory effect of N-Arg. CONCLUSIONS: Nitric oxide mediates the C5a
      induced vasodilation in small intestinal microvessels. Superoxide is, at least
      partially, responsible for the vasoconstrictor response to C5a in the presence of
      N-Arg.

PMID- 8542541
TI  - Adverse drug reactions and drug substitution in an arrhythmia clinic.
AB  - OBJECTIVE: To assess the impact of adverse drug reactions on antiarrhythmic drug
      substitution in ambulatory patients. SETTING: Tertiary care dysrhythmia clinic.
      PATIENTS AND METHODS: A total of 671 medical records were reviewed. Sex of the
      study population was equally distributed, with an average age of 53 years. Follow
      up averaged 26 months for patients seen more than once. Suspected adverse drug
      reactions and substitution of antiarrhythmic agent were used to ascertain events
      in patients' charts. Patients were exposed to 1253 treatment courses. The number
      of successive antiarrhythmic agents per patient averaged 1.8 and varied from one
      to seven. RESULTS: One hundred and thirty-nine (20%) patients experienced a total
      of 194 adverse events (15.5% of drug courses), of which only eight (4%) were
      serious. Ninety-four per cent of the mostly benign adverse drug reactions were
      followed by a therapeutic modification: discontinuation or replacement in 87% and
      dosage reduction in 7%. The influence of successive drug changes was evident: the
      risk of a reaction was 7% in patients exposed to one agent compared with 100% in
      patients exposed to a seventh agent. CONCLUSIONS: First, therapeutic substitution
      in response to adverse drug reactions appears to be determined more by the
      combined expected benefit, the product of arrhythmia severity and drug efficacy,
      than by the severity alone of the adverse reaction; and second, the probability
      of an adverse drug reaction is proportional to the number of agents tried
      consecutively, possibly as a result of patient selection, drug selection and
      increased patient and doctor awareness.

PMID- 8542542
TI  - A new, simple and accurate method for determining ejection fraction by Doppler
      echocardiography.
AB  - OBJECTIVE: To evaluate the feasibility, accuracy and reproducibility of a new and
      simple method for determining ejection fraction by Doppler echocardiography. This
      method should theoretically be less influenced by the distortions of left
      ventricular geometry caused by prior myocardial infarction. DESIGN: Two groups of
      patients (total 114) were evaluated independently at the Quebec and Ottawa Heart
      Institutes (60 and 54 patients, respectively). All were referred for radionuclide
      angiography performed within 24 h of the echocardiogram. Regional asynergy was
      present in 59% of Quebec patients and 37% of Ottawa patients. The new method for
      calculating ejection fraction consisted of dividing Doppler derived stroke volume
      in the left ventricular outflow tract by left ventricular end-diastolic volume
      calculated by Teichholz's formula; for comparison, ejection fraction was also
      measured by single plane area length or multiple disc planimetry as well as by
      the Quinones method at the Quebec Heart Institute. RESULTS: Feasibility of the
      new method was 97% in Quebec and 100% in Ottawa. Compared with radionuclide
      angiography, the correlation coefficient for the new method was 0.92 (standard
      error of estimate [SEE] = 7.3) in Quebec compared with 0.88 (SEE = 8.5 and 8.1)
      for both the Quinones and single plane area length methods, and 0.84 (SEE = 12.0)
      in Ottawa compared with 0.77 (SEE = 10.9) for the single plane multiple disc
      method. Correlations in patients with regional asynergy were 0.90 in Quebec and
      0.75 in Ottawa compared with 0.81 and 0.54 with planimetry. Correlation
      coefficients for interobserver variability in 12 patients were 0.97 with the new
      method compared with 0.83 with the Quinones method and 0.85 with single plane
      planimetry. CONCLUSION: This new and simple method is feasible, accurate and
      reproducible even in patients with regional asynergy. Provided there is no
      significant mitral regurgitation, it is a time-saving alternative for the routine
      evaluation of ejection fraction by Doppler echocardiography.

PMID- 8542543
TI  - Elevated platelet-derived microparticle levels during unstable angina.
AB  - OBJECTIVE: To use fluorescent-activated flow cytometry coupled with activation
      dependent and -independent platelet-specific monoclonal antibodies in a pilot
      study to assess the degree and time course of platelet activation events in
      patients presenting within 24 h of onset of Canadian Cardiovascular Society class
      4 angina. BACKGROUND: Although activated platelets play a key role in the
      pathogenesis of unstable angina, the development of simple assays to quantify
      platelet activation events directly is lacking. METHODS: Blood samples were drawn
      from six unstable angina patients from the coronary care every 4 h over a 24 h
      period into a fixative and analyzed the following day. All patients were on
      acetylsalicylic acid and heparin. Comparisons were made with six healthy,
      medication-free volunteers. Platelets were defined by flow cytometry as positive
      for fluorochrome-labelled monoclonal antibody to glycoprotein Ib (AP1) and within
      the single intact platelet window defined by scatter characteristics. The
      presence of the fluorochrome-labelled activation-specific monoclonal antibody
      (KC4.1 for anti-P-selectin, PAC-1 for activated glycoprotein IIb/IIIa) was used
      to determine the percentage of activated platelets. Platelet activation-dependent
      microparticles were identified by gating on AP1-positive events and defining
      microparticles (percentage of total platelet events) as being smaller (forward
      size scatter) than single intact platelets. RESULTS: There was a marked, sixfold
      increase in microparticle generation (17 +/- 7% versus 2.8 +/- 1.4%) in the
      unstable angina patients (P = 0.001) compared with healthy volunteers. Further
      assessment of six coronary care unit patients with nonischemic cardiac disorders
      demonstrated a highly variable intermediate level of microparticle generation (11
      +/- 7%). No differences in activated glycoprotein IIb/IIIa expression were noted
      for the various groups and P-selectin expression was lower in the unstable angina
      patients (6 +/- 2% versus 12 +/- 3%, (P = 0.007). CONCLUSIONS: This pilot study
      suggests that measuring circulating platelet microparticle levels is a simple yet
      useful parameter for the assessment of platelet activation in unstable angina
      compared with activation markers on intact whole platelets. Despite antiplatelet
      and antithrombin therapy, significant platelet activation occurred in these
      patients over the initial 24 h. Flow cytometry may be a useful tool in assessing
      the efficacy of newer therapeutic modalities.

PMID- 8542544
TI  - Evidence of type 2 herpes simplex infection in human coronary arteries at the
      time of coronary artery bypass surgery.
AB  - OBJECTIVE: To examine histologically biopsies from the coronary arteries of
      patients undergoing coronary artery bypass grafting (CABG) for evidence of herpes
      simplex virus type 1 (HSV-1) and type 2 (HSV-2) antigen and to correlate the
      incidence with pathological and clinical data. DESIGN: Sequential patients
      undergoing CABG in whom adequate tissue could be obtained for histology. SETTING:
      University teaching hospital. PATIENTS: Forty-six patients were enrolled. Thirty
      one provided sufficient tissue and clinical information for the analysis.
      METHODS: Biopsy material was collected in the operating room and prepared
      immediately for histology and electron microscopy. Slides were prepared by
      staining with hematoxylin and eosin, Masson trichrome, avidin biotin complex
      immunoperoxidase for HSV-1 and HSV-2 protein and specific DNA probes for HSV-1
      and HSV-2 by hybridization. Clinical data were obtained in structured interviews.
      RESULTS: Sixty-one per cent of biopsies demonstrated evidence of inflammation,
      45% were positive for antigen to HSV-2 and only one to HSV-1. Significant
      positive correlations were detected between inflammatory cells in the biopsy and
      a recent history of cold sores and between the presence of the infiltrate and
      positivity to HSV-2 antigen. CONCLUSION: A correlation exists between HSV-2
      infection and the inflammatory response associated with atherosclerosis.

PMID- 8542545
TI  - One hundred years ago: Oscar Langendorff and the birth of cardiac metabolism.

PMID- 8542546
TI  - Angiographic underestimation of coronary artery disease in a cardiac transplant
      donor.
AB  - There has been a great deal of attention given to the development of post
      transplant arteriopathy in the cardiac transplant patient. Preexisting donor
      heart disease may be of equal importance in the development of allograft failure
      due to ischemia. The case of a 64-year-old female who received the heart of a 52
      year-old female is reported. Death of the recipient occurred due to
      intraoperative complications. Despite normal pretransplant coronary angiography,
      autopsy found severe atherosclerotic coronary artery disease in the donor heart.
      This case report illustrates some of the limitations of angiography in the
      detection of coronary artery lesions in donor hearts.

PMID- 8542547
TI  - The importance of and issues in vascular disease.

PMID- 8542548
TI  - Trends in pediatric cardiac pacing.
AB  - OBJECTIVE: To review retrospectively a 31-year experience with pediatric cardiac
      pacing at the University of Toronto, with an emphasis on the changing trends in
      pacemaker implantation in infants and children. DATA SOURCE: Data were obtained
      from the pediatric pacemaker follow-up clinic at The Hospital for Sick Children,
      Toronto, Ontario or from the referring pediatric centre. Follow-up was normally
      continued until the death of the child or referral to an adult hospital at age 18
      years. PATIENT SELECTION: The study comprised 397 children (under 18 years of
      age) who underwent initial pacemaker implantation at The Hospital for Sick
      Children between January 1962 and December 31, 1992. Follow-up was 99% complete
      (five children lost) and ranged from one month to 32 years (mean 6.5 years). DATA
      SYNTHESIS: The use of endocardial versus epicardial leads increased significantly
      over time (P < 0.001). In addition, significantly more children receiving
      pacemakers had sick sinus syndrome (P < 0.001). No difference in survival was
      found between children paced by endocardial versus epicardial leads or between
      children paced for sick sinus syndrome versus atrioventricular block. The
      frequency of exit block, by lifetable analysis, did not differ between children
      who received epicardial versus endocardial leads. CONCLUSIONS: Guidelines for
      permanent pacemaker implantation in children continue to evolve as developments
      in lead technology alter trends in pediatric cardiac pacing.

PMID- 8542549
TI  - Comparative study of two trehalase activities from Fusarium oxysporum var. lini.
AB  - Acid and neutral trehalase activities (optimum pH of 4.6 and 6.8, respectively)
      from Fusarium oxysporum var. lini were studied separately through partial
      isolation by ammonium sulfate precipitation followed by ion-exchange
      chromatography on DEAE-Sephacel for neutral enzyme, or using some of their
      differential properties. Acid activity was unaffected by 1 mM of Ca2+, Mg2+,
      Mn2+, Ba2+, or EDTA. Contrarily, the neutral enzyme was activated by Ca2+ with an
      apparent Ka of 0.15 mM; was inhibited by EDTA, Zn2+, Hg2+, or Mg(2+)-ATP; and
      showed an increase in activity by the raise of buffer ionic strength or by the
      addition of 100 mM KCl. Acid and neutral enzymes have, respectively, an apparent
      optimum temperature of 45 and 30 degrees C, an apparent Km for trehalose of 0.43
      and 8.45 mM, and an apparent M(r) of 160,000 and 100,000 (by glycerol gradient
      ultracentrifugation). Acid trehalase was specifically inhibited by acetate buffer
      and more stable at 50 degrees C than the neutral enzyme. Neutral enzyme exhibited
      a pI of 6.2 by isoelectric focusing. Contrary to neutral trehalases from other
      fungi, the enzyme from Fusarium oxysporum var. lini was not activated in crude
      extract by treatment with Mg(2+)-ATP in the presence of cAMP and not inactivated
      by alkaline phosphatase from Escherichia coli.

PMID- 8542550
TI  - Water activity, temperature, and pH effects on growth of Fusarium moniliforme and
      Fusarium proliferatum isolates from maize.
AB  - The effects of water activity (aw, 0.994-0.90 identical to 0.4-14.0 (-)MPa water
      potential), temperature (4-45 degrees C), and pH (3.6, 5.5, 7.0), and their
      interactions on growth of isolates of Fusarium moniliforme and Fusarium
      proliferatum were determined in vitro on a maize extract agar medium. Growth of
      two isolates of F. moniliforme and four isolates of F. proliferatum were
      significantly influenced by water activity regardless of solute type used (NaCl,
      glycerol, or glucose). However, at steady-state aw levels, growth was optimum at
      0.994-0.98 aw and reduced significantly at 0.92 aw. Further detailed studies with
      one isolate of F. moniliforme (25N) and two isolates of F. proliferatum (73N,
      131N) showed that growth occurred over the range of 0.994-0.90 aw in the
      temperature range 20-35 degrees C with slight differences between species. Growth
      did occur at 4 degrees C and 0.994-0.96 aw, but no growth was recorded at 40 and
      45 degrees C regardless of aw. Profiles of aw x temperature relations for growth
      of these two species were constructed from these data for the first time. Optimum
      pH and temperature for growth was 5.5 and 25 degrees C for both isolates of F.
      proliferatum, and pH 7.0 and 30 degrees C for the isolate of F. moniliforme.
      However, for the latter isolate at < 0.98 aw, optimum pH and temperature for
      growth changed. The effects of pH, temperature, and aw for single, two-way and
      three-way interactions were all found to be statistically significant for these
      three isolates. The ecological significance of this information for understanding
      these important fumonisin-producing fungi is discussed.

PMID- 8542551
TI  - Microbial ecology of simultaneous thermophilic microbial leaching and digestion
      of sewage sludge.
AB  - The microbial population encountered during a simultaneous thermophilic microbial
      leaching and digestion process at 50 degrees C, based on microbial sulfur
      oxidation, was investigated. The cell count of the sulfuric acid producer
      Thiobacillus thermosulfatus increased, followed by a decrease. In the absence of
      sulfur (control: conventional thermophilic digestion), Thiobacillus
      thermosulfatus population decreased under the detection limit. Acidophilic and
      neutrophilic heterotrophic populations increased during the leaching process, and
      the final acidophilic population count was higher than the neutrophilic
      population. During the thermophilic digestion (control), the final neutrophilic
      population count was higher than the acidophilic. Six heterotrophic bacterial
      strains were isolated and partially characterized. Bacillus was the most
      predominant genus. The type of bacterial populations in thermophilic microbial
      leaching and digestion, as well as the thermophilic digestion process (control),
      were the same, while only the relative concentrations changed. In both processes,
      the bacterial indicators decreased under the detection limit after 12 h.
      Mesophilic heterotrophic population was more affected by the thermophilic
      microbial leaching process than by thermophilic digestion. Sludge mineralization
      was probably more influenced by the final cell concentration rather than the
      presence of an individual species or mixed population.

PMID- 8542552
TI  - Oligonucleotide probes based on 16S rRNA sequences for the identification of four
      Azospirillum species.
AB  - Partial sequences of the 16S rRNA molecules of nine strains belonging to four
      Azospirillum species were used to design species-specific oligonucleotide probes.
      Azospirillum strains sequences were analyzed and three homologous fragments
      containing 16 nucleotides were determined. These three probes were found to be
      characteristic of A. lipoferum (Al), A. irakense (Ai), and A.
      brasilense/amazonense species (Aba) and of few nontarget organisms. The
      specificity of these three probes was tested both against sequences in the
      GenBank data base and in numerous colony hybridization experiments. As a few non
      target organisms hyridized with the different Azospirillum probes, the use of
      these probes in bulk soil hybridization is not permitted. However, their use
      together with specific isolation techniques is validated.

PMID- 8542553
TI  - Alterations in cell pigmentation, protein expression, and photosynthetic capacity
      of the cyanobacterium Oscillatoria tenuis grown under low iron conditions.
AB  - To better describe the iron-limited nutrient status of aquatic photosynthetic
      microorganisms, we examined the effects of iron limitation on pigment content,
      maximum rates of photosynthetic oxygen evolution, and respiratory oxygen
      consumption in the filamentous cyanobacterium Oscillatoria tenuis Ag. Within the
      range of iron (4.2 x 10(-5)-5.1 x 10(-9) M FeCl3), growth rates were not limited
      by photosynthetic capacity but rather by another, as of yet undetermined, iron
      requiring cellular function. We have also investigated membrane proteins that are
      induced when the cells are grown in low iron medium. Using membrane fractionation
      techniques we were able to recognize specific proteins localized in the outer
      membrane and periplasmic space of O. tenuis. The recovery of growth rates at low
      iron levels occurred in parallel with the induction of these proteins and the
      production of extracellular siderophores. The additional iron acquired by this
      high affinity transport system did not reestablish photosynthesis in O. tenuis to
      the iron-satiated level but did reestablish growth to iron-replete levels.
      Oscillatoria tenuis appears to invoke an alternate physiology to compensate for
      iron deficiency.

PMID- 8542554
TI  - Description of two new species of Halomonas: Halomonas israelensis sp.nov. and
      Halomonas canadensis sp.nov.
AB  - Six well-known strains of halotolerant bacteria, including two strains previously
      identified only as NRCC 41227 and Ba1, have been compared using 125 phenotypic
      characters and DNA-DNA hybridization. Although these strains represent some of
      the most heavily studied salt-tolerant bacteria, they have never been
      taxonomically compared. The data presented show that these bacteria form a
      relatively homogeneous group related at the genus level. The taxonomic comparison
      showed that these six organisms represented four distinct species all related
      above the 65% Jaccard coefficient level. In addition to two previously identified
      bacterial species, Halomonas elongata (ATCC 33173T) and Halomonas halodurans
      (ATCC 29686T), the strains included in this study represent two previously
      unnamed Halomonas species. These two new taxa have been assigned the names
      Halomonas israelensis (ATCC 43985T) and Halomonas canadensis (NRCC 41227T = ATCC
      43984). DNA-DNA hybridization show that these two species are related to the type
      species H. elongata at 54.9 and 48.9%, respectively.

PMID- 8542555
TI  - Detection of additional restriction fragment length polymorphisms among the
      weakly virulent (nonaggressive) and highly virulent (aggressive) isolates of
      Leptosphaeria maculans.
AB  - Isolates of Leptosphaeria maculans were analyzed for their genetic relatedness
      based on DNA restriction fragment length polymorphisms (RFLPs), employing as
      Southern hybridization probes a combination of heat shock responsive genes (hsp70
      and hsp80 from Neurospora crassa), the cutinase gene of Magnaporthe grisea, and
      cloned genomic DNA sequences from a virulent strain. Southern hybridization
      analysis revealed a high frequency of DNA polymorphism. Restriction fragments
      generated by each enzyme-probe combination resulted in distinct banding patterns,
      clearly separating the isolates into two groups. The cutinase gene probe did not
      reveal any polymorphisms. Although the majority of the probes used displayed RFLP
      profiles unique to each group, a nonaggressive isolate, LmA, showed additional
      genetic characteristics in common with the virulent pathotype.

PMID- 8542556
TI  - Production and rheological properties of a succinoglycan from Pseudomonas sp.
      31260 grown on wood hydrolysates.
AB  - Pseudomonas sp. ATCC 31260 produced substantial amounts of anionic extracellular
      polysaccharide (EPS) from a mineral acid hydrolysate of wood, prepared using the
      "Tennessee Valley Authority" process. Partially purified EPS production
      approached 16.5 g/L (as hexadecyltrimethylammonium bromide precipitate) when the
      pH of the hydrolysate was initially adjusted to 7.5 and amended with 0.05% each
      of peptone and yeast extract. This EPS, now characterized as a succinoglycan, is
      composed of glucose, galactose, succinate, pyruvate, and acetate. Solutions of
      this EPS are pseudoplastic, and under specified conditions, are rheologically
      comparable with commercially available xanthan.

PMID- 8542557
TI  - Gun control.

PMID- 8542558
TI  - Gun control.

PMID- 8542559
TI  - Could zinc help protect children from lead poisoning?

PMID- 8542560
TI  - Complementary medicine and the scientific method.

PMID- 8542561
TI  - Complementary medicine and the scientific method.

PMID- 8542562
TI  - Common drugs and the progress of cancer.

PMID- 8542563
TI  - Nitroglycerin as a "cardiac-arrest" extinguisher.

PMID- 8542564
TI  - Do Canadian female surgeons feel discriminated against as women?
AB  - OBJECTIVE: To describe female surgeons' perceptions of discrimination against
      them as women during the selection and training process and in career development
      and advancement, and to describe trends over time. DESIGN: Population survey of
      practising Canadian female surgeons. SETTING: Canada. PARTICIPANTS: All 459
      female members in good standing of the Royal College of Physicians and Surgeons
      of Canada or the Corporation professionnelle des medecins du Quebec, or both,
      practising in Canada as of March 1990. Participants completed a survey between
      March 1990 and May 1992, the response rate was 91% (419/459). OUTCOME MEASURES:
      Reported levels of discrimination during selection and training and in career
      development and advancement, institutional policies on maternity leave and job
      sharing, and the existence of female role models or mentors. RESULTS:
      Discrimination during the process of selection for residency was reported by 15%
      (63/413) of the respondents. Just over half of the respondents (206/405) reported
      male attending staff as being discriminatory during training, and 41% (168/407)
      reported nursing staff as being discriminatory. Almost half of the respondents
      (199/408) indicated that discrimination did not hinder their career development
      or advancement at all, and 29% (118) indicated that it had little effect. Almost
      two thirds (245/381) reported no maternity leave policies during residency or
      practice, and 78% (296/379) reported having no job-sharing opportunities.
      Although 82% (338/413) agreed that female medical students need female role
      models, 80% (330/415) reported they did not have a female mentor. CONCLUSIONS:
      Although most of our respondents perceived no discrimination in their selection
      for residency and reported that discrimination did not hinder their career
      development or advancement, the perception of discrimination during surgical
      training suggests that there needs to be a concentrated effort to identify and
      address problems. Moreover, since few respondents reported having institutional
      policies on maternity leave and job-sharing or female mentors, these issues need
      to be examined.

PMID- 8542565
TI  - Effectiveness of notification and group education in modifying prescribing of
      regulated analgesics.
AB  - OBJECTIVE: To compare the effectiveness of group education and notification with
      that of notification alone in modifying prescribing of regulated analgesics.
      DESIGN: Randomized controlled trial conducted from Dec. 1, 1992, to Dec. 31,
      1993. SETTING: Nonacademic primary care practices in British Columbia.
      PARTICIPANTS: Fifty-four physicians randomly selected from a group of 100
      physicians who had written a number of prescriptions for regulated drugs more
      than than two standard deviations above the mean number of prescriptions written
      for such drugs in 1992. Any physician who was unable to participate was replaced
      from the original group of 100 before the study began. Five subjects did not
      complete the study and were not included in the analysis. INTERVENTIONS:
      Participants were randomly assigned to three groups: those in the first group
      received a written notification of excessive prescribing and attended a 1-day
      group-education activity, those in the second group received a written
      notification of excessive prescribing only and those in the third group were not
      subject to any intervention and were unaware that their prescribing had received
      special notice. OUTCOME MEASURE: Mean number of prescriptions for regulated
      analgesics issued per physician in the 6 months before and the 6 months after the
      interventions. RESULTS: Physicians in the group that attended the education
      intervention wrote, on average, 33% fewer prescriptions after the intervention,
      whereas physicians in the group that received only written notification wrote 25%
      fewer prescriptions, on average, after the intervention. No change in prescribing
      was shown in the control group. The differences in rates of prescribing of
      regulated analgesics between each intervention group and the control group were
      statistically significant (p < 0.01). The difference in the rate of prescribing
      between the two intervention groups was not significant. CONCLUSIONS: Group
      education and notification of prescriber status as well as notification alone
      significantly reduced prescribing of regulated analgesics. Hence, feedback on a
      physician's prescribing pattern may be a practical and less costly alternative to
      direct educational intervention in moderating the prescribing of regulated
      analgesics. The results do not, however, imply that notification is as effective
      as education in improving overall patient care. A follow-up study comparing the
      duration of the effect of the educational intervention with that of notification
      alone is warranted.

PMID- 8542566
TI  - Habit, prejudice, power and politics: issues in the conversion of H2-receptor
      antagonists to over-the-counter use.
AB  - H2-receptor antagonists have been widely prescribed in the last 20 years and are
      considered to rank among the safest drugs known. In several countries they have
      been switched to over-the-counter (OTC) status, and a similar move is under
      consideration in Canada. Some concerns have been raised as to the effectiveness
      of these drugs in the treatment of dyspepsia and heartburn, their safety when
      taken for self-diagnosed symptoms, and the potential for their use to delay
      diagnosis or mask serious disease. The author presents evidence to support the
      use of OTC H2-receptor antagonists in the treatment of dyspepsia. He argues that
      the safety record of these drugs is reassuring and that they are unlikely to mask
      gastric cancer. Finally, he describes the appropriate place of OTC H2-receptor
      antagonists in the overall management of acid-related disorders.

PMID- 8542567
TI  - On-campus physicians witnessing changes in medical problems faced by university
      students.
AB  - Most Canadian universities offer on-campus health services for their students.
      Ten years ago minor health problems such as infections, cuts and bruises were the
      common causes of visits to student health centres, but today medical staff report
      that students are seeking help for more serious problems such as sexually
      transmitted diseases, stress, sports injuries, eating disorders and asthma and
      allergies. Many are also seeking psychiatric counselling.

PMID- 8542568
TI  - Triviality and frequency of night calls irk British GPs.
AB  - British general practitioners, who are tired of their 24-hour responsibility,
      recently had a showdown with government about providing medical care outside
      normal hours. Physicians will be paid more for after-hours calls, but many would
      prefer not to do the work at all. They say such calls are often a waste of their
      time.

PMID- 8542569
TI  - Physicians say government-approved love affair with gambling sure bet to cause
      problems.
AB  - There has been an abrupt change in Canadians' attitudes toward gambling. Almost
      all forms of gambling used to be illegal, but cash-strapped governments have
      recognized this new and healthy source of revenue and have become the biggest
      bookies in the country. Gil Kezwer sought responses from physicians and gambling
      experts about the implications of Canada's love affair with all types of
      gambling.

PMID- 8542570
TI  - UBC researcher's back-pain studies focus on space travel.
AB  - Researchers at the University of British Columbia have been studying back pain
      that develops in astronauts in space. Their findings not only may help astronauts
      cope with future space travel, but also lead to new treatments for Earth-bound
      patients who experience back pain.

PMID- 8542571
TI  - Corporation seeks contracts, projects for Canadian firms in global health care
      market.
AB  - An Ontario-based corporation is acting as a general contractor for about 50
      Canadian firms interested in the international marker for health care services
      and products. After less than 1 year of operation, the firm had identified
      potential opportunities for Canadian firms to sell their expertise in providing
      primary health care services and developing national disease-prevention programs.
      Another promising niche for Canadian firms and researchers in the global
      marketplace is the development and sale of rehabilitation products.

PMID- 8542572
TI  - Expression of the human mismatch repair gene hMSH2 in normal and neoplastic
      tissues.
AB  - Hereditary nonpolyposis colorectal cancer is caused by inherited mutations of
      mismatch repair genes. We developed monoclonal antibodies to the prototype human
      mismatch repair gene hMSH2 and used them to detect an immunoreactive protein of
      M(r) 100,000 in mismatch-proficient cell lines. In addition, a M(r) 150,000
      protein coimmunoprecipitated with the hMSH2 gene product in cell lines expressing
      hMSH2. Immunohistochemistry demonstrated that the hMSH2 protein was exclusively
      nuclear. Whereas the hMSH2 protein was expressed in a variety of tissues, the
      most striking pattern was observed in esophageal and intestinal epithelia, where
      expression was limited to the replicating compartment. Neoplastic cells within
      benign and malignant mismatch repair-proficient tumors expressed the protein, but
      no hMSH2 immunoreactivity was observed in the colorectal tumors of patients with
      germline hMSH2 mutation. These results have implications for tumorigenic
      mechanisms and, potentially, for diagnosis.

PMID- 8542573
TI  - Escape from senescence in hybrid cell clones involves deletions of two regions
      located on human chromosome 1q.
AB  - Human normal cells have been shown to undergo a limited number of cell doublings,
      a phenomenon termed cellular senescence. Human chromosome 1 has been implicated
      in this process, and several lines of evidence indicate that there is a
      senescence-inducing gene or genes on human chromosome 1q. Our approach to analyze
      the senescence-inducing effect of chromosome 1 includes the use of somatic cell
      hybrid revertants. We show here that fusion of a hypoxanthine phosphoribosyl
      transferase-negative mouse cell line (A9) containing a human neo-tagged
      chromosome 1 with an immortal hamster cell line (10W-2) results in cell hybrids
      that senesce after a few population doublings. Rare revertants that had escaped
      senescence were obtained after one large fusion experiment. Thirty-five
      nonsenescent hybrids were obtained from a total of approximately 1 million
      hybrids, and 25 of these were subjected to further analysis. The presence of a
      single copy of human chromosome 1 in the revertant hybrids was confirmed by
      fluorescence in situ hybridization analysis using a chromosome 1-specific
      painting probe. No visible translocations or deletions of chromosome 1 were
      observed in any of the hybrids. Deletion mapping revealed that 11 (56%) of the
      hybrids analyzed had lost one or more markers on chromosome 1q. Two regions with
      deletions were detected, one of which has been shown to be implicated in the
      senescence-inducing effect exerted by chromosome 1 following monochromosome
      transfer (P. J. Vojta et al., manuscript submitted for publication). The present
      study suggests that two separate loci on human chromosome 1q may be of importance
      for the induction of senescence. Moreover, this set of nonsenescent revertants
      could be useful for future detailed analyses of the senescence-inducing loci.

PMID- 8542574
TI  - The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes murine
      fibroblasts and human tumor cells to radiation and blocks induction of p53
      following DNA damage.
AB  - AT cells are extremely sensitive to ionizing radiation. Since the AT gene has
      homology to phosphatidylinositol 3 kinases (PI 3-kinases), wortmannin, a specific
      inhibitor of PI 3-kinase, was used to determine if PI 3-kinase activity regulates
      radiation sensitivity. Human and murine cells exposed to wortmannin alone did not
      display significant cytotoxicity. Wortmannin in combination with radiation was an
      effective radiosensitizer of murine NIH-3T3 fibroblasts, with a sensitizer
      enhancement ratio of 1.8 at 10% survival, and had a similar effect on the human
      tumor cell lines HeLa, SW480, and MCF-7. Wortmannin inhibited the induction of
      p53 DNA-binding activity by actinomycin D and radiation and blocked the
      transcriptional activation of a p53 CAT reporter gene by actinomycin D.
      Wortmannin radiosensitized both wild-type (NIH-3T3 and MCF-7) and mutant (SW480
      and HeLa) p53 cells, indicating that p53 induction was not required for
      radiosensitization by wortmannin. The results suggest that a wortmannin-sensitive
      pathway, possibly involving PI 3-kinase activity, may regulate the response of
      the cells to DNA damage.

PMID- 8542575
TI  - The effect of tobacco on lung cancer risk depends on CYP2D6 activity.
AB  - The genetically determined P450 CYP2D6 activity is suspected to be involved in
      lung carcinogenesis by activating carcinogens contained in tobacco smoke.
      Therefore, lung cancer risk should depend on both smoking exposure and CYP2D6
      activity. The extent to which CYP2D6 activity, determined by using
      dextromethorphan, could modify the effect of tobacco was evaluated from a study
      on 128 lung cancers and 157 controls. A strong interaction was observed; the
      effect of tobacco on lung cancer risk rose with increasing CYP2D6 activity (P <
      0.001). Increasing levels of smoking increased lung cancer risk only among
      smokers with the highest CYP2D6 activity, and CYP2D6 was a risk factor only among
      heavy smokers. Smokers with both the highest CYP2D6 activity and daily tobacco
      consumption were at very high risk for lung cancer. These results may explain
      discrepant results of previous studies on the association between CYP2D6 activity
      and lung cancer.

PMID- 8542576
TI  - A cysteine proteinase, which cleaves human C3, the third component of complement,
      is involved in tumorigenicity and metastasis of human melanoma.
AB  - The DM-4 human melanoma cell line, which is highly metastatic in nude mice,
      expresses a C3-cleaving activity that proteolyzes labeled as well as unlabeled
      human C3. This C3-cleaving activity is a cysteine proteinase characterized by a
      M(r) 41,000. The p41 proteinase shares antigenic determinants with murine p39
      procathepsin-L and human procathepsin-L. Preincubation of DM-4 cells with anti
      p39 F(ab')2 induced up to 45% decrease in their complement resistance.
      Pretreatment of DM-4 cells with anti-p39 Ab strongly inhibited their
      tumorigenicity and significantly decreased their metastatic potential in nude
      mice. Thus, the p41 C3-cleaving proteinase contributes to tumorigenicity and
      metastasis of human melanoma DM-4 cells.

PMID- 8542577
TI  - Ubiquitous somatic alterations at microsatellite alleles occur infrequently in
      Barrett's-associated esophageal adenocarcinoma.
AB  - Microsatellite alterations have been documented in a subset of sporadic tumors,
      including those of the colon, lung, bladder, stomach, and esophagus. This study
      documented the frequency of microsatellite alterations at 139 loci, comprising
      predominantly dinucleotide and tetranucleotide repeat units, in 17 cases of
      primary esophageal adenocarcinoma arising against a background of Barrett's
      metaplasia. Each tumor demonstrated alterations in at least one locus studied.
      Widespread microsatellite alterations, occurring at 45.3% (58 of 128) of loci
      tested, were detected in a single case. The remaining 16 tumors exhibited low
      levels of microsatellite instability, ranging from 0.8% (1 of 128) to 8.1% (10 of
      123) of loci tested. The single case with ubiquitous somatic alterations showed
      no significant difference in the incidence of novel alleles at di- and
      tetranucleotide repeat loci. The 16 cases showing a low level of microsatellite
      alterations demonstrated a 3.3-fold higher incidence of novel alleles at
      tetranucleotide repeat loci compared to dinucleotide repeat loci. These data
      suggest that ubiquitous somatic alterations at microsatellite loci, considered a
      phenotypic expression of defective mismatch repair, occur infrequently in
      Barrett's-associated adenocarcinoma. However, the majority of these tumors
      demonstrate a low level of microsatellite alterations, perhaps reflecting the
      inherent instability of these markers.

PMID- 8542578
TI  - Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block
      induced by 1,25-dihydroxyvitamin D3 in HL60 cells.
AB  - Progression of mammalian cells through G1 is controlled by the concerted action
      of protein kinases, the activities of which are modulated in both positive
      (cyclins) and negative [cyclin-dependent kinase inhibitors (CDIs)] manners by
      families of regulatory proteins. In differentiation of leukemia cells, a G1
      arrest is a common, if not invariable, occurence and takes place after the
      appearance of markers of monocytic differentiation in human leukemia HL60 cells
      treated with 1,25 dihydroxyvitamin D3 (1,25D3) at low to moderately high
      concentrations (F. Zhang et al., Cell Proliferation 27: 643-654, 1994). In the
      present study, we investigated the protein levels of several G1 regulatory
      proteins that are potential mediators of the 1,25D3-induced G1 block. During the
      first 24 h of exposure to a high concentration (4 x 10(-7) M) of 1,25D3, no
      increase was noted in the immunodetectable levels of cyclins D1 or E, or CDIs
      p16Ink4, p21Cip1/Waf1, or p27Kip1, even though monocytic differentiation markers
      were evident, and a prolongation of G1 was noted. After 48 h of exposure 4 x 10(
      7) M to 1,25D3, a G1 to S-phase block progressively increased in parallel with
      the abundance of the p27Kip1 CDI. A transient increase in p21Cip1/Waf1 was noted
      only at 48 hr. The increase in p27Kip1 protein level was dependent on the
      concentration of 1,25D3 and was accompanied by an increase in cyclin D and E
      proteins, which normally peak in mid-G1 and at the G1 to S-phase transition,
      respectively. These results indicate that p27Kip1 protein is a strong candidate
      for the cell cycle regulator that blocks the entry into the S-phase in 1,25D3
      treated HL60 cells.

PMID- 8542579
TI  - Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach.
AB  - Loss of heterozygosity (LOH) at several chromosomal loci is a common feature of
      the malignant progression of human tumors. In the case of chromosome 11, LOH has
      been well documented in several types of solid neoplasms, including gastric
      carcinoma, suggesting the presence of suppressor gene(s) at 11p15 and 11q22-23.
      Little is currently known about the molecular events occurring during the
      development of gastric cancer. To define the regions of chromosome 11 involved in
      gastric cancer progression, we used high-density polymorphic markers to screen
      for LOH in matched normal and tumor tissue DNA from 60 primary gastric
      carcinomas. We found that 21% of the tumors showed LOH simultaneously at 11p15
      and 11q22-23, 41% had LOH at 11p15, and 30% had LOH at 11q22-23. We confirm that
      the minimal critical area of LOH for 11p15.5 is the approximately 2-Mb region
      between loci D11S1318 and D11S988. However, when we analyzed the pattern of LOH
      according to the country of origin of the patient, LOH for 11q22-23 alone was
      found only in cases from Italy. The minimal critical region of LOH at 11q22-23 is
      identical to that identified for other solid tumors, suggesting that the same
      putative tumor suppressor gene(s) contained within this region is involved in the
      pathogenesis of several common human tumors.

PMID- 8542580
TI  - HSP27 phosphorylation-mediated resistance against actin fragmentation and cell
      death induced by oxidative stress.
AB  - Phosphorylation of heat shock protein 27 (HSP27) has been suggested to play an
      important role in the regulation of F-actin dynamics in response to growth
      factors and stress. Because the microfilament network is one of the earliest
      targets of oxidative stress and because phosphorylation of HSP27 is strongly
      induced by reactive oxygen metabolites, we have investigated the role of HSP27
      phosphorylation in regulating actin dynamics in response to oxidative stress.
      Experiments were done in Chinese hamster CCL39 cells overexpressing various
      levels of the wild-type or a nonphosphorylatable form of human HSP27 (pm3 HSP27).
      In control cells, both H2O2 and menadione induced fragmentation of F-actin, which
      forms aggregates and patches concentrated around the nucleus. Stable
      overexpression of wild-type HSP27, but not of pm3 HSP27, conferred resistance
      against actin fragmentation, suggesting that HSP27 has a phosphorylation
      activated protective function against actin disruption by oxidative stress. Cell
      lines that overexpressed the highest levels of the wild-type form of human HSP27
      also showed an increased cell survival following exposure to H2O2. In contrast,
      cells expressing pm3 HSP27 were as sensitive as the controls to the lethal effect
      of H2O2. These results suggest that phosphorylation of HSP27 is causally related
      to the regulation of microfilament dynamics following oxidative stress and may be
      involved in mediating an adaptive response to oxyradical-generating agents such
      as carcinogens, anticancer drugs, and other xenobiotics.

PMID- 8542581
TI  - Platelet-derived growth factor-B/v-sis confers a tumorigenic and metastatic
      phenotype to human T98G glioblastoma cells.
AB  - Autocrine stimulation by platelet-derived growth factor-B (PDGF-B)-like factors
      has been widely implicated as an important mechanism in the cause and/or
      maintenance of a variety of human tumors. However, normal human cells appear to
      be resistant to transformation by PDGF-B-like molecules, and a direct
      demonstration of the tumor-promoting or tumor-maintaining property of a PDGF-B
      autocrine system is lacking. T98G human glioblastoma cells are nontumorigenic in
      athymic mice. We show that these cells express predominantly PDGF-beta type
      receptors and continuously secrete small amount of PDGF-B/c-sis. Addition of
      suramin or specific anti-PDGF-B/v-sis antibody inhibits proliferation in culture.
      Conversely, multiple clonal lines that stably overexpress PDGF-B/v-sis (T98Gsis
      cells) exhibit a striking 200-250% increased proliferation rate and an enhanced
      colony-forming frequency in soft agar. Clonal lines with stable expression of
      PDGF-B/v-sis (T98Gsis cells) reliably (80%) develop tumors in 4-6 weeks, whereas
      the empty-vector control cells are nontumorigenic. Moreover, in some cases,
      T98Gsis cells disseminate to form bilateral and multifocal pulmonary metastases.
      The results show that T98G cells contain functional PDGF receptors that, upon
      sufficient stimulation, can cause greatly increased mitogenic response, which may
      account for the development of the malignant phenotype. Metastatic tumor
      formation in athymic mice by PDGF stimulation has not been reported previously.
      The mechanism may depend on preexisting changes such as the lost p53 function of
      these cells. T98Gsis cells provide a model of growth factor-dependent
      tumorigenesis and metastases, which may be helpful in elucidating these
      relationships.

PMID- 8542583
TI  - p53 mutations in bladder tumors from arylamine-exposed workers.
AB  - In this study we compared the frequency and pattern of p53 mutations in 34
      bladder tumors from people with high-level occupational exposure to arylamines to
      those in 30 bladder tumors from people without such exposure. No differences were
      observed for p53 mutations between the two groups. The frequency of mutation was
      similar at 47% for arylamine-exposed individuals and 53% for unexposed
      individuals and showed a similar pattern of mutation, with GC to AT transitions
      accounting for the majority of the mutations in both groups. This finding
      suggests that arylamine exposure does not leave a mutational "footprint" in the
      p53 gene. However, compared to other tumors, bladder tumors from both exposed and
      unexposed individuals had a high frequency of multiple mutations and it is
      interesting that these mutations were highly concordant. We suggest that one
      explanation of this pattern of mutations could be from decreased DNA repair
      fidelity within tumor cells. The frequency of mutation in p53 is closely linked
      to tumor grade and stage and so may be a late event in the development of bladder
      tumors.

PMID- 8542582
TI  - Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to
      breast cancer etiology.
AB  - The etiology of the majority of human breast cancers is unknown. Environmental
      factors have long been suspected to play a role, but no specific causative agent
      has been identified. If the hypothesis that environmental carcinogen exposure
      contributes to human breast cancer is true, carcinogen-DNA adducts would be
      expected to be present in human breast tissues. To address this possibility,
      aromatic DNA adducts were measured in 87 surgical specimens of normal human
      breast tissues from 87 breast cancer patients undergoing mastectomy using the
      nuclease P1-enhanced version of the 32P postlabeling assay. Breast tissue samples
      from 29 noncancer patients undergoing reduction mammoplasty served as controls.
      Whereas aromatic DNA adducts were detected in all tissue samples examined, the
      total adduct levels in cancer patients were significantly higher than that in
      noncancer controls [mean +/- SEM, 97.4 +/- 23.4/10(9) nucleotides (range, 3.8
      1737.1) versus 18.1 +/- 11.6/10(9) nucleotides (range, 5.6-56.7), respectively; P
      < 0.01, t test and Mann-Whitney test]. This difference was not affected by the
      age distribution of the two groups. The typical smoking-related DNA adduct
      pattern (i.e., a diagonal radioactive zone) was observed in 29 of 87 tissues (17
      of 17 current smokers, 5 of 8 former smokers, 4 of 52 nonsmokers, and 3 of 10
      patients with unknown smoking status) and in 2 of 10 control tissues. It was of
      interest that a benzo(a)pyrene (BP)-like DNA adduct was observed in 36 normal
      adjacent breast tissues (41%), 27 of which were from nonsmokers. Levels of this
      BP-like adduct were extremely high (> 100/10(9) nucleotides) in 5 patients (4
      nonsmokers and 1 smoker) and moderately high (> 10/10(9) nucleotides) in 13 other
      patients (8 nonsmokers and 5 smokers). One patient exhibited this adduct at a
      level of 1500/10(9) nucleotides, which is comparable to the highest level of
      total adducts reported in human tissues related to carcinogen exposure (e.g.,
      cigarette smoking). In contrast, this adduct was absent (< 1/10(9) nucleotides)
      in all of the control tissues. Cochromatography and rechromatography analysis of
      DNA samples from human breast tissues and from MCF-7 cells treated with BP
      revealed that this adduct could be generated by BP exposure but is not the major
      BP 7,8-diol-9,10-epoxide-deoxyguanine adduct detected previously in animal
      tissues and human mammary epithelial cells. These findings support the hypothesis
      that environmental carcinogen exposure, in addition to cigarette smoking, may be
      associated with the etiology of human breast cancer.

PMID- 8542585
TI  - Altered cJUN expression: an early event in human lung carcinogenesis.
AB  - Although the c-jun oncogene is an integral part of the AP-1 transcriptional
      complex implicated in the process of tumor promotion, its role in the
      pathogenesis of human tumors is unknown. We analyzed the expression and function
      of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors,
      histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines
      to examine the role of cJun in lung carcinogenesis. cJun was expressed in primary
      and metastatic lung tumors in 31% of cases, with no association with survival.
      Whereas normal conducting airway and alveolar epithelial in general did not
      express cJun by immunohistochemistry, histologically atypical areas were
      frequently positive for cJun, regardless of the status of the corresponding
      tumor. Multiple members of the jun and fos gene families were frequently
      expressed at the mRNA level in vitro, with detectable functional activity (as
      defined by AP-1-specific DNA binding and/or transactivation of an AP-1-driven
      reporter construct) present in all 10 NSCLC cell lines examined. Although tumor
      promoting phorbol esters had little effect on c-jun expression, serum stimulation
      generally resulted in significant c-jun induction in NSCLC cell lines. These data
      show that cJun expression is altered early during human lung carcinogenesis and
      that cJun may function as a mediator of growth factor signals in NSCLC.

PMID- 8542584
TI  - Development of human cytochrome P450-expressing cell lines: application in
      mutagenicity testing of ochratoxin A.
AB  - With the aim to assess the involvement of distinct forms of cytochrome P450
      enzymes in the activation of procarcinogens, we have developed by means of
      retroviral infection a series of NIH/3T3 cell lines stably expressing human
      CYP1A1, CYP1A2, CYP2C10, CYP2D6, and CYP2E1 cDNA. The levels of cytochrome P450
      enzyme activities were determined using specific substrates. An increase in
      specific catalytic activity could be observed in all cell lines compared to
      background activity in vector-infected cells. Furthermore, we developed a test
      system in which we are able to combine P450-expressing cells with a shuttle
      vector containing the lacZ' gene, which serves as a reporter gene for mutations.
      Using this system, we investigated the cytotoxicity and mutagenicity of the
      mycotoxin ochratoxin A. Natural occurrence of ochratoxin A in food commodities
      has been linked to an increased incidence of urinary tract tumors in certain
      geographic regions. Although biotransformation seems to play a crucial role in
      ochratoxin A toxicity, the possible contribution of metabolites to genotoxicity
      and carcinogenicity remained unelucidated. We have demonstrated that the mutation
      frequency of ochratoxin A was increased dependent upon concentration in NIH/3T3
      cell lines, stably expressing human CYP1A1, CYP1A2, CYP2C10, and CYP3A4. In
      contrast, neither in vector-infected NIH/3T3 cells nor in CYP2D6- and CYP2E1
      expressing cells was an increase of mutation frequency observed.

PMID- 8542586
TI  - Metabolism of 5-methylchrysene and 6-methylchrysene by human hepatic and
      pulmonary cytochrome P450 enzymes.
AB  - The metabolism of environmentally occurring methylated polynuclear aromatic
      hydrocarbons by human cytochrome P450 (P450) enzymes has not been examined
      previously. We compared the metabolism of the tobacco smoke constituents 5
      methylchrysene (5-MeC), a strong carcinogen, and 6-MeC, a weak carcinogen, in 18
      hepatic and 11 pulmonary human microsomes. Major metabolites of 5-MeC were its
      proximate carcinogen trans-1,2-dihydroxy-1,2-dihydro-5-methylchrysene (5-MeC-1,2
      diol), as well as 5-MeC-7,8-diol, bay region dihydrodiols, and phenols. 5-MeC-1,2
      diol and 5-MeC-7,8-diol were formed stereoselectively, with the R,R enantiomers
      predominating. Major metabolites of 6-MeC were 6-MeC-1,2-diol, bay region
      dihydrodiols, phenols, and 6-(hydroxymethyl)chrysene. 6-MeC-1,2-diol was also
      formed stereoselectively in the 1R,2R configuration. All human liver samples
      formed the proximate carcinogenic 1,2-diols (0.2-2.3 pmol/mg protein/min for 5
      MeC and 0.3-3.1 pmol/mg protein/min for 6-MeC). Comparable results were obtained
      in pulmonary microsomes, but the extent of metabolism was less than in the
      hepatic samples, and only 4 of 11 samples showed activity. Catalytic activities
      known to be associated with specific P450s were analyzed in each hepatic sample
      and correlated with levels of 5-MeC and 6-MeC metabolites in the same samples.
      The results of the correlation analysis indicated that P450s 1A1 and 1A2 were
      active in the formation of 5-MeC-1,2-diol and 6-MeC-1,2-diol, as well as several
      other metabolites resulting from ring oxidation. The formation of the
      hydroxymethyl metabolites was catalyzed by P450 3A4 (for 5-MeC) or P450s 3A4 and
      1A2 (for 6-MeC). Experiments with chemical inhibitors and antibodies supported
      these results. The metabolism of 5-MeC and 6-MeC was also investigated using
      purified recombinant human P450s 1A1, 1A2, 2C10, 2D6, 2E1, 3A4, and 3A5. P450s
      1A1, 1A2, and 2C10 had higher activities than the other enzymes for ring
      oxidation of 5-MeC and 6-MeC, whereas P450s 1A2 and 3A4 were more active than the
      other enzymes for methyl hydroxylation of 6-MeC. Only P450 3A4 showed substantial
      catalytic activity for methyl hydroxylation of 5-MeC. Collectively, the results
      of these studies demonstrate that P450s 1A2 and 2C10 are important catalysts of
      the metabolic activation of 5-MeC and 6-MeC in human liver, whereas P450 1A1
      plays a major role in the metabolic activation of these compounds in human lung.

PMID- 8542587
TI  - Expression of alpha-1,3-fucosyltransferase type IV and VII genes is related to
      poor prognosis in lung cancer.
AB  - To date, five alpha-1,3-fucosyltransferase genes (Fuc-TIII, IV, V, VI, and VII)
      have been cloned. To examine the role of alpha-1,3-fucosyltransferase in the
      synthesis of sialyl Lewis x and the prognosis of lung cancer, PCR amplification
      of five fucosyltransferase genes and immunohistochemical staining of sialyl Lewis
      x were performed in 333 patients with lung cancer who underwent surgical
      resection from 1980 to 1993. The frequencies of Fuc-TIII/V, Fuc-TVI, Fuc-TIV, and
      Fuc-TVII expression were 9%, 26%, 75%, and 66%, respectively. The frequency of
      sialyl Lewis x expression (75%) was comparable to Fuc-TIV and Fuc-TVII
      expression. However, the grading of sialyl Lewis x staining correlated only with
      the grading of Fuc-TVII gene amplification. Survival of the patients whose tumors
      showed strong expression of Fuc-TIV and/or FucT-VII was significantly shorter
      than that of the patients whose tumors did not express either Fuc-TIV or Fuc
      TVII. These results suggest that Fuc-TIV and Fuc-TVII expression may be of
      prognostic value among patients with lung cancer by participating in the
      biosynthesis of sialyl Lewis x.

PMID- 8542588
TI  - Genetic evidence for the Lewis enzyme, which synthesizes type-1 Lewis antigens in
      colon tissue, and intracellular localization of the enzyme.
AB  - To determine whether the Lewis enzyme responsible for the Lewis blood type
      antigens on erythrocytes synthesizes the Lewis antigens on normal cells and
      cancer cells in colon tissue, we performed genotyping of the Lewis gene by the
      PCR-RFLP method and by immunohistochemical staining of Lewis antigens and the
      Lewis enzyme with specific monoclonal antibodies (mAbs) in colon tissues obtained
      from 100 colon cancer patients. Five of the 100 patients were identified as
      homozygotes for the mutant Lewis gene, i.e., the le/le genotype that cannot
      encode functional Lewis enzyme. The cells in both the normal and cancerous
      regions of colon tissue from these five le/le patients were completely devoid of
      staining with mAbs against Lewis antigens with the type 1 chain, i.e., Lewis a,
      Lewis b, and sialyl Lewis a. In contrast, the cells in cancerous regions of the
      colon tissue of the 95 patients with the Le/Le or Le/le genotype positively
      stained with all three mAbs, anti-Lewis a, anti-Lewis b, and anti-sialyl Lewis a.
      The cells in the cancerous regions of the colon tissue of the five le/le patients
      stained with DU-PAN-2 mAb, whose recognizing epitope is known to be sialyl Lewis
      c, a precursor structure of sialyl Lewis a. By immunohistochemical staining with
      FTA 1-16 mAb, which is directed at the human Lewis enzyme, we were able to
      demonstrate for the first time that the enzyme is localized in the Golgi area of
      the colon epithelial cells of patients with the Le/Le or Le/le genotype. No
      staining was observed in the Golgi area of the cells of the patients with the
      le/le genotype. From these results, we conclude that individuals with the Le/Le
      or Le/le genotype possess a functional Lewis enzyme synthesizing fucosylated type
      1 Lewis antigens in the Golgi apparatus of the colon epithelial cells, but that
      individuals with the le/le genotype are devoid of the Lewis enzyme in the Golgi
      apparatus, resulting in an inability to synthesize Lewis antigens with the type-1
      chain, and that it is inappropriate to use CA19-9, whose antigenic epitope is
      defined as sialyl Lewis a, as a tumor marker in patients with the le/le genotype.

PMID- 8542589
TI  - Induction of tumor necrosis by delta-aminolevulinic acid and 1,10-phenanthroline
      photodynamic therapy.
AB  - delta-Aminolevulinic acid (ALA) causes cells to accumulate protoporphyrin IX
      (Proto) and heme. Exposure to light in vitro causes intracellular Proto to
      initiate formation of singlet oxygen molecules, leading to self-destruction. This
      photoactivated destruction by ALA in vitro is enhanced by addition of the
      tetrapyrrole modulator 1,10-phenanthroline (Oph), which increases cellular
      accumulation of Proto. Here we significantly extend this idea by evaluating the
      efficacy of ALA and Oph photodynamic therapy of solid tumors in vivo.
      Methylcholanthrene-induced fibrosarcoma (Meth-A) cells were used, which lead to
      the formation of solid tumors when implanted into syngeneic recipients.
      Initially, suspensions of Meth-A cells were treated in vitro with combinations of
      ALA and Oph. Meth-A cells in suspension accumulated 6-fold greater amounts of
      Proto (P < 0.05) after 3-h incubation with ALA and Oph than when incubated with
      ALA alone, and were also more susceptible to subsequent photoactivated cell lysis
      in vitro. Similarly, solid Meth-A tumors grown in syngeneic BALB/c mice
      accumulated significant (P < 0.05) amounts of Proto 3 h after in vivo treatment
      with ALA, and Oph synergized with ALA to significantly (P < 0.05) enhance the
      induction of Proto in these tumors. ALA and Oph-based phototreatment of mice
      bearing Meth-A solid tumors resulted in necrosis of tumors, as determined by a
      significant reduction in both size and histopathology, with little damage to
      surrounding normal tissue. These data directly demonstrate the experimental
      usefulness of Proto modulators for ALA-based photodynamic therapy in the
      treatment of solid tumors in vivo and provide a rationale for their potential
      application in a multitude of tumor types.

PMID- 8542590
TI  - Camptothecin resistance involving steps subsequent to the formation of protein
      linked DNA breaks in human camptothecin-resistant KB cell lines.
AB  - To identify mechanisms of camptothecin (CPT) resistance/toxicity, sublines from a
      human KB cell line were made resistant to CPT by continuous selection in
      increasing concentrations of CPT. Two CPT-resistant lines, 100 and 300, were 32-
      and 54-fold resistant to the growth-inhibitory properties of CPT compared to the
      KB line. After CPT-free culturing, partial revertant lines were established from
      each resistant line. These partial revertant lines, 100rev and 300rev, were 2.5-
      and 3.2-fold resistant to CPT compared to KB. When growth inhibition and toxicity
      were compared, the resistant lines alone displayed an enhanced cytostatic
      response to CPT. The resistant and partial revertant lines displayed no cross
      resistance to etoposide or cisplatin. Comparisons of topoisomerase I (TOPI)
      activity, content, and protein-linked DNA break production by CPT revealed that
      resistant and partial revertant lines had one-half the levels as KB, with TOP1
      activity that was equally sensitive to CPT in all cell lines tested. However,
      double-stranded DNA break induction by CPT was significantly reduced only in the
      resistant lines. Coincubation with 3-aminobenzamide, an inhibitor of poly(ADP
      ribosyl) polymerase, potentiated CPT toxicity in the resistant lines alone,
      without affecting CPT: TOP1 interactions. Therefore, CPT resistance in the 100
      and 300 lines was characterized by factors independent of TOP1, specific for CPT,
      and attenuated by poly(ADP-ribosyl) polymerase inhibition. This resistant
      phenotype produced fewer double-stranded DNA breaks and enhanced a cytostatic
      response to CPT.

PMID- 8542591
TI  - Eradication of Myc-overexpressing small cell lung cancer cells transfected with
      herpes simplex virus thymidine kinase gene containing Myc-Max response elements.
AB  - Herpes simplex virus thymidine kinase (HSV-TK) gene was ligated with four repeats
      of the Myc-Max response elements (a core nucleotide sequence CACGTG), and its
      utility for gene therapy was examined by the treatment of either c-, L- or N-myc
      overexpressing the small cell lung cancer (SCLC) cell line with ganciclovir
      (GCV). The chloramphenicol acetyltransferase assay demonstrated that the
      overexpression of any myc genes activated transcription from the CAT gene
      depending on the Myc-Max binding sites. The transduction of the HSV-TK gene
      ligated with the CACGTG core rendered all three SCLC lines to be more sensitive
      to GCV than parental ones in vitro. In addition, the growth of c- or L-myc
      overexpressing SCLC cells containing the hybrid HSV-TK gene were significantly
      suppressed by GCV in vivo. When parental SCLC cells were mixed with HSV-TK
      expressing tumor cells at a ratio of 1:3, GCV treatment inhibited tumor growth by
      90% compared with parental cells only, indicating the existence of the "bystander
      effect." These data suggest that the CACGTG-driven HSV-TK gene may be useful for
      the treatment of SCLC overexpressing any type of myc family oncogenes.

PMID- 8542592
TI  - In vitro and in vivo inhibition of glioblastoma and neuroblastoma with MDL101731,
      a novel ribonucleoside diphosphate reductase inhibitor.
AB  - We examined the effects of MDL101731, a novel ribonucleoside reductase inhibitor,
      against human glioblastomas and neuroblastoma, both in vitro and in xenograft
      models, to determine its activity against malignant brain tumors. MDL101731
      produced a concentration-dependent inhibition of both glioblastoma cell lines
      (HS683 and J889H) and neuroblastoma (SK-N-MC) in nanomolar concentrations (IC50,
      30-90 nM). s.c. xenografts of human glioblastoma (D54) in athymic mice increased
      to five times their initial volume at a median of 7.4 days in control animals,
      while tumor regression occurred in 12 of 12 animals treated with MDL101731 (100
      mg/kg, i.p., two times/week) during 22 days of treatment (P < 0.0001).
      Intracerebral implants of D54 carried a median survival of 20 days in control
      animals, whereas animals receiving MDL101731 (100 mg/kg, i.p., two times/week,
      days 10-35) had a median survival of 46.5 days (P < 0.0001). Intracerebral
      xenografts of SK-N-MC in athymic mice resulted in a median survival of 23 days in
      control animals and 26 days in animals treated with carmustine (1,3-bis(2
      chloroethyl)-1-nitrosourea 20 mg/kg/week, i.v. x 2; difference not significant).
      There was 90% survival in animals treated with MDL101731 (200 mg/kg, i.v., two
      times/week, days 7-35) up to 90 days after implant. These studies indicate that
      MDL101731 has potent antiproliferative activity against human malignant brain
      tumors.

PMID- 8542593
TI  - T-cell receptor repertoire in neuroblastoma patients.
AB  - Spontaneous regression of widespread lesions is a characteristic feature of
      neuroblastoma. One may postulate that the immune response contributes to these
      clinical regressions. Accordingly, we studied the T-cell receptor (TCR)
      repertoire of tumor-infiltrating lymphocytes in eight neuroblastoma tumors. The
      expression of 29 V alpha and 24 V beta gene segment subfamily specificities was
      analyzed by PCR and compared by computerized densitometry of Southern blots to
      values obtained in the blood. Overall, the TCR repertoire of these eight patients
      was diverse, with virtually all V alpha and V beta specificities expressed.
      Nonetheless, four of these patients showed V beta 2 gene segment subfamily
      overexpression in the tumor corresponding to local expansion of polyclonal T-cell
      subpopulations. In one patient, this expansion could be due to local secretion of
      superantigenic activity, as suggested by the specific stimulation of murine T
      cells expressing a human V beta 2 chain by supernatant of the corresponding
      neuroblastoma cell line. In addition, high-resolution analysis of the TCR beta
      transcript complementarity-determining region 3 sizes identified three patients
      (of six studied) with marked clonal T-cell expansion in the tumor not seen in the
      blood. The specific expression of several dominant clono-types in the tumor may
      be related to the recognition of neuroblastoma-specific antigens in these
      patients. Together, these results on the TCR repertoire expressed in vivo may
      lead to the characterization of putative immune response mechanisms (i.e.,
      antigen- or superantigen-driven stimulation) which participate in tumor
      regression.

PMID- 8542594
TI  - Autocrine growth of small cell lung cancer mediated by coexpression of c-kit and
      stem cell factor.
AB  - At least 70% of small cell lung cancer (SCLC) tumors and tumor-derived cell lines
      coexpress the genes for stem cell factor (SCF) and its receptor, the c-kit proto
      oncogene. To assess the impact of coexpression of the growth factor and receptor
      on SCLC growth, the NCI-H146 SCLC cell line, which expresses only SCF, was
      transfected with a c-kit expression vector. Kit protein immunoprecipitated from
      the transfected cells had a constitutive level of tyrosine phosphorylation, and
      these cells grew more vigorously in serum-free medium compared to control
      transfected cells. This growth advantage could be blocked by the addition of the
      tyrosine kinase inhibitor herbimycin A. Growth of the c-kit-transfected cells
      could be further enhanced by the addition of bombesin or insulin-like growth
      factor-1, suggesting that the SCF/c-kit autocrine loop could function
      cooperatively with other SCLC autocrine loops. To further investigate the
      importance of this autocrine loop, a cell line that naturally coexpresses SCF and
      c-kit was transfected with a kinase-defective c-kit gene. Cells transfected with
      the defective gene showed a marked decrease in their ability to grow under growth
      factor-free conditions compared to cells transfected with the empty expression
      vector. Taken together, these studies demonstrate that the coexpression of the
      stem cell factor and c-kit genes is a major contributor to the growth factor
      independence of SCLC.

PMID- 8542595
TI  - Predominant expression of human zic in cerebellar granule cell lineage and
      medulloblastoma.
AB  - Zic is a novel zinc finger protein which displays a highly restricted expression
      pattern in the adult and developing mouse cerebellum and is highly homologous to
      the recently cloned Drosophila pair-rule gene Opa. To clarify the mechanism for
      the development of the human cerebellum and its involvement in human nervous
      system diseases, we have isolated human Zic cDNA and examined its expression by
      using monoclonal antibody against recombinant Zic protein. The nucleotide
      sequence of human Zic cDNA is 85% homologous to that of mouse Zic cDNA. Its
      putative amino acid sequence is highly conserved (> 99%) except for substitution
      of only two amino acid residues. In situ chromosome hybridization localized the
      human Zic gene to chromosome band 3q24. Human Zic protein was
      immunohistochemically detected in the nuclei of the cerebellar granule cell
      lineage from the progenitor cells of the external germinal layer to the
      postmigrated cells of the internal granular layer. Furthermore, Zic protein was
      detected in medulloblastoma (26/29 cases), whereas no other tumors examined (over
      70 cases including primitive neuroectodermal tumors) expressed this protein.
      These findings suggest that Zic is a potential biomarker for medulloblastoma as
      well as the human cerebellar granule cell lineage.

PMID- 8542596
TI  - Differential expression of membrane-type matrix metalloproteinase and its
      correlation with gelatinase A activation in human malignant brain tumors in vivo
      and in vitro.
AB  - In this study, we investigated the expression of activated gelatinase A and
      membrane-type metalloproteinase (MT-MMP) induced by concanavalin A (ConA) in four
      highly invasive glioma cell lines (UWR2, UWR3, U251MG, and SNB-19). We also
      examined gelatinase A and MT-MMP expression in human brain tumor tissues in vivo.
      Gelatin zymography showed that all four cell lines expressed latent progelatinase
      A (M(r) 66,000). Activated gelatinase A (M(r) 62,000) was induced by ConA in only
      UWR2 or UWR3 cells. MT-MMP mRNA was present in all four cell lines prior to ConA
      treatment, and the relative hybridization signals were 1, 0.80, 0.25, and 0.15 in
      UWR2, UWR3, U251MG, and SNB-19 cells, respectively. These mRNA signals were
      dramatically increased (2,8-, 5.4-, and 2.2-fold in UWR2, UWR3, and U251MG cells,
      respectively) following ConA treatment; however, MT-MMP mRNA expression was
      unchanged in SNB-19 cells. MT-MMP protein was detected in various amounts in the
      four cell lines, but only after ConA pretreatment. The amount of MT-MMP mRNA was
      unchanged in SNB-19 after ConA treatment, and the MT-MMP mRNA level in ConA
      treated U251MG was lower than in UWR2 and UWR3 without ConA treatment. MT-MMP
      protein was detected in SNB-19 and U251 cell lines only after ConA treatment.
      Gelatin zymography of human brain tumor tissues revealed that almost all samples
      examined contained a latent form of gelatinase A, whereas the activated form of
      gelatinase A was only seen in metastatic lung adenocarcinomas and malignant
      astrocytomas, and especially in glioblastomas. MT-MMP mRNA levels were
      significantly higher in malignant astrocytomas than in low-grade gliomas and
      normal brain tissues. These results were confirmed by PCR analysis, which showed
      that MT-MMP mRNA was absent or barely detectable in normal brain white matter but
      was easily detectable in malignant astrocytomas. Immunohistochemistry of MT-MMP
      in frozen sections showed that MT-MMP was localized in neoplastic astrocytes of
      malignant astrocytomas but was undetectable in normal white brain matter. The
      data indicate that MT-MMP is present in malignant human glial tumors and that MT
      MMP expression correlates with expression and activation of gelatinase A during
      malignant progression in vivo. A direct correlation between the levels of MT-MMP
      protein and its transcripts was not found in vitro, suggesting that MT-MMP
      expression in glioma cell lines might be regulated either at the level of
      transcription message stability or at posttranscription. Altered MT-MMP
      expression might contribute, in part, to gelatinase A activation, which in turn
      facilitates invasion of these tumors.

PMID- 8542597
TI  - Inhibition of growth of C6 glioma cells in vivo by expression of antisense
      vascular endothelial growth factor sequence.
AB  - Tumor angiogenesis involves a combination of events including the production of
      inhibitors, proteases, and angiogenic factors that have a chemotactic and
      mitogenic effect on endothelial cells. Vascular endothelial growth factor (VEGF)
      is an endothelial cell-specific mitogen that promotes angiogenesis in solid
      tumors, including brain tumors such as astrocytomas. As an approach to the
      development of new strategies for gene therapy of brain tumors, we have
      interrupted the VEGF/VEGF receptor paracrine pathway in an attempt to inhibit
      angiogenesis and thereby control tumor growth. Rat C6 glioma cells were
      transfected with a eukaryotic expression vector bearing an antisense-VEGF cDNA.
      Stable transfectants were observed to express reduced levels of VEGF in culture
      under hypoxic conditions. When implanted s.c. into nude (nu/nu) mice, growth of
      the antisense-VEGF cell lines was observed to be greatly inhibited compared to
      control cells, despite the fact that they have a faster division time in vitro.
      Analysis of these tumors revealed that they have fewer blood vessels and a higher
      degree of necrosis, which is a plausible explanation for the reduced tumor size.
      We believe antisense-VEGF can be successfully used to control tumor growth and
      may provide the basis for the development of antiangiogenic gene therapy.

PMID- 8542598
TI  - Contiguous patches of normal human mammary epithelium derived from a single stem
      cell: implications for breast carcinogenesis.
AB  - Tissue clonality can be assessed in females by analyzing the methylation status
      of polymorphic DNA markers on X-linked genes because extensive de novo
      methylation of one allele at the preimplantation stage is associated with its
      permanent inactivation. We applied X chromosome inactivation toward understanding
      human breast morphogenesis by examining the nonmalignant breast epithelium from
      two reduction mammaplasties and a mastectomy. We found that entire lobules and
      large ducts of normal breast tissue have the same X chromosome inactivated,
      suggesting that they are derived from the same stem cell. The regions of
      inactivation of a particular X chromosome do not extend over an entire breast, so
      that ducts and lobules with opposite chromosomes inactivated are present within a
      single breast. Potential relevance of these observations for malignant
      transformation is discussed.

PMID- 8542599
TI  - 2-Nitroimidazole (EF5) binding predicts radiation resistance in individual 9L
      s.c. tumors.
AB  - The presence of hypoxic tumor cells is known to be an important cause of
      radiation treatment resistance in vivo. The ability to predict the presence and
      extent of hypoxic cells in individual tumors would allow the addition of specific
      "antihypoxia"-based treatment regimes. Hypoxia can be monitored by measuring the
      binding of 2-nitroimidazoles. We have tested the hypothesis that binding of EF5,
      a fluorinated derivative of the 2-nitroimidazole, Etanidazole, can predict
      radioresistance in individual tumors. Fischer rats bearing 9L s.c. tumors were
      given injections i.v. with EF5 3 h before irradiation and tumor harvest. Tumor
      cells were dissociated for flow cytometric analysis and plating efficiency
      studies. EF5 binding was detected via monoclonal antibodies conjugated to the
      orange emitting dye, Cy3. In air breathing rats, for a given radiation dose, a
      large amount of variation in plating efficiency was seen. However, there was
      minimal variability of the plating efficiency for tumors irradiated in euthanized
      animals (hypoxic tumors; correlation coefficient for the fitted curve = 0.93) and
      in cells dissociated from tumors and irradiated in suspension (correlation
      coefficient for the fitted curve = 0.99), suggesting that varying sensitivity to
      the cell disaggregation technique was not responsible. In contrast, a good
      correlation between the relative radiation resistance or hypoxic survival and EF5
      binding of "moderately" hypoxic cells in air breathing rats was identified using
      these techniques. In these 9L s.c. tumors, intertumor variation in oxygenation
      accounted for most of the range in individual tumor radiation response, and this
      was found to be independent of tumor size. This study provides evidence for the
      application of EF5 binding with monoclonal antibody detection as an in vivo
      predictive assay of individual tumor hypoxia and resultant therapy resistance.

PMID- 8542600
TI  - Bisecting N-acetylglucosamine on K562 cells suppresses natural killer
      cytotoxicity and promotes spleen colonization.
AB  - beta 1-4 N-acetylglucosaminyltransferase (GnT-III) catalyzes the formation of
      bisecting N-acetylglucosamine (GlcNAc) in the biosynthesis of N-linked
      oligosaccharides. To examine the effect of bisecting GlcNAc on the natural killer
      (NK) cytotoxicity, the GnT-111 gene was introduced into NK-sensitive K562 cells
      that have no detectable GnT-III activity. We obtained three clones stably
      expressing high GnT-III (positive transfectants). Introduction of the GnT-III
      gene resulted in an increase of bisecting GlcNAc and a decrease of external
      sialic acid as well as tri- and tetraantennary sugars, as judged by flow
      cytometry. Compared to controls, the NK cytotoxicity was completely blocked
      against positive transfectants. The binding of effector cells to positive
      transfectants was also decreased. After s.c. injection into nude mice, positive
      transfectants produced spleen colonization, although no spleen lesions were
      formed by control cells. In nude mice depleted of NK cells by anti-asialo GM1
      antibody, both positive transfectants and controls produced spleen colonization
      equally. These results indicate that K562 cells expressing GnT-III are resistant
      to NK cytotoxicity, resulting in spleen colonization in nude mice.

PMID- 8542601
TI  - Detection of immunoglobulin/c-myc recombinations in mice that are resistant to
      plasmacytoma induction.
AB  - Interchromosomal recombinations between c-myc and immunoglobulin sequences can be
      found in preneoplastic lesions (oil granulomata) during pristane-induced
      plasmacytoma development in susceptible BALB/cAn mice. In this study we used a
      more sensitive approach, hybridization-enriched templates with nested PCR, to
      detect microclones with Ig alpha/c-myc recombinations in oil granulomata of
      susceptible and resistant mice. Recombinations were detected in as many as 73%
      (32/44) of plasmacytoma-susceptible BALB/cAn mice 30 days after an injection of
      pristane. Mice that are resistant to plasmacytoma induction can also harbor
      recombination-positive cells, but these are less frequent [2/20 DBA/2N, 8/20
      (BALB/cAn x DBA/2N)F1, hereafter called CD2F1]. The clones in DBA/2N mice were
      small (< 400 cells), whereas in BALB/cAn, the oil granuloma harbored up to
      several thousand of these cells. We conclude that the molecular machinery for
      generating characteristic interchromosomal recombinations can be found in all
      strains of mice. Both the frequency of generating Ig alpha/c-myc recombinations
      and the expansion of recombination-positive cells are greater in susceptible mice
      than in resistant strains.

PMID- 8542602
TI  - A self-included cyclomaltoheptaose derivative studied by NMR spectroscopy and
      molecular modelling.
AB  - The 3D structure of 6-deoxy-6-L-tyrosinylamidocyclomaltoheptaose, a self
      complexing beta-cyclodextrin derivative, was determined by NMR and molecular
      modelling. The aminoacyl side-chain is included in the cavity and induces
      chemical-shift variations in the CD proton signals, allowing their complete
      assignment. Dipolar interactions between protons of the tyrosine ring and
      internal protons of the cyclodextrin were used to obtain distance constraints.
      Then 42 structures were calculated from 32 distance constraints--21 shorter than
      4 A involve the host-guest interactions--using a simulated annealing procedure.
      Starting from one of the resulting structures, a 250-ps molecular dynamics
      simulation was carried out in a waterbox without constraint. The simulation data
      are in agreement with NMR data such as nOe and ring-current effects. The
      cyclodextrin part takes an elliptical shape, which tightly fits the aromatic
      moiety. As a consequence, the respective motion of the host and the guest
      moieties have the same amplitude and time scale: the self-inclusion complex shows
      only little flexibility.

PMID- 8542603
TI  - Synthesis of fluorescent and radioactive analogues of two lactosylceramides and
      glucosylceramide containing beta-thioglycosidic bonds that are resistant to
      enzymatic degradation.
AB  - Condensation of 2-S-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-2-
      thiopseudourea hydrobromide with 2,3,6-tri-O-benzoyl-4-O-trifluoromethylsulfonyl
      beta-D-galactopyra nosyl- (1-->1)-(2S,3R,4E)-3-O-benzoyl-2-dichloroacetamido-4
      octa decen-1,3-diol afforded S-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)
      (1-->4)-2,3,6-tri-O- benzoyl-4-thio-beta-D-glucopyranosyl-(1-->1)-(2S,3R,4E)-3-O
      benzoy l-2- dichloroacetamido-4-octadecen-1,3-diol in good yield. Removal of the
      protecting groups, followed by selective N-acylation of the sphingosine amino
      group with either a fluorescent or a radioactive fatty acid, gave labeled
      lactosylceramide analogues in good yield. Since these products contained a beta
      thioglycosidic bond between the two sugar moieties, they were totally resistant
      to the action of acid lysosomal glycosidases. Likewise, condensation of 2-S
      (2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-2- thiopseudourea hydrobromide and
      2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1-->4)-2,3,6- tri-O-acetyl-1-S
      acetyl-1-thio-beta-D-glucopyranose with (2R,3R,4E)-3-O-benzoyl-2
      dichloroacetamido-1-iodo-4-octad ecen-3-ol in methanolic sodium acetate afforded
      the corresponding beta-thioglycosides 14 and 16, respectively, in good yield.
      These beta-thioglycosides were converted into glucosylceramide and
      lactosylceramide analogues following removal of the protecting groups and by
      subsequent selective N-acylation using either a fluorescent or adioactive fatty
      acid N-succinimidyl ester. Whereas the glucosylthioceramides thus obtained proved
      to be completely undegradable by lysosomal glucocerebrosidase, the
      lactosylceramides containing the beta-thioglycosidic bond between the lactose and
      the ceramide residues could be degraded by lysosomal GM1-beta-galactosidase to
      give the corresponding glucosylthioceramides. These compound did not yield to any
      further enzymatic degradation.

PMID- 8542604
TI  - Synthesis of uridine-5-propylamine derivatives and their use in affinity
      chromatography of N-acetylglucosaminyltransferases I and II.
AB  - The C-5 substituted uridine derivatives UDP-5-propylamine (7) and UDP-GlcNAc-5
      propylamine (8) were synthesized in good yields by Heck alkylation of the 5
      mercuriuridines, followed by hydrogenation. The products were characterized by 1H
      and 13C NMR spectroscopy, electrospray mass spectrometry and UV
      spectrophotometry. The amines are of interest for the preparation of affinity
      probes for glycosyltransferases. The benzoylbenzamides of 7 and 8 show strong
      competitive inhibition of N-acetylglucosaminyltransferase I and II with Ki values
      ranging from 30 to 100 microM (without irradiation) and may be useful as active
      site-directed photoaffinity labels. A conjugate of 8 and Sepharose was used for
      affinity chromatographic purification of N-acetylglucosaminyltransferases I and
      II. The results indicate that this affinity gel is a stable alternative to the
      commonly used but unstable UDP-GlcNAc-5-Hg-thiopropyl conjugate.

PMID- 8542605
TI  - Synthesis and 1H NMR characterization of the six isomeric mono-O-sulfates of 8
      methoxycarbonyloct-1-yl O-beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy
      beta-D-glucopyran oside.
AB  - All six isomeric mono-O-sulfates of beta-D-Galp-(1-->4)-beta-D-GlcpNAc-O
      (CH2)8COOMe (LacNAc-MC) have been chemically synthesized and characterized by
      high resolution 1H NMR spectroscopy. Sulfation causes characteristic substitution
      site-specific downfield shifts of 1H NMR signals. The 4C1 chair conformation of
      both pyranose residues of LacNAc are unaffected by mono-O-sulfation, and, with
      the exception of the 3-O-sulfate derivative, glycosidic torsion angles are also
      unaffected.

PMID- 8542606
TI  - Structure of the O-deacetylated glucuronoxylomannan from Cryptococcus neoformans
      serotype C as determined by 2D 1H NMR spectroscopy.
AB  - The primary structure of the O-deacetylated capsular glucuronoxylomannan (GXM)
      isolated from Cryptococcus neoformans serotype C was investigated by 2D NMR
      spectroscopy. Assignment of the 1H NMR chemical shifts for the polysaccharide was
      accomplished from the analysis of DQF-COSY, TOCSY, NOESY and/or ROESY spectra of
      three isolates (298, 34, and 401). These isolates contain the same polysaccharide
      glycosyl residues but in different proportions. The serotype C GXM consists of
      two repeating polysaccharide units that have the following structures: [formula:
      see text] It is not known if these repeating units comprise a single or two
      separate polymer chains. The relative amounts of the more highly branched
      octasaccharide 1 in the isolates studied (i.e., approximately 75% in isolate 34,
      50% in isolate 298, and 25% in isolate 401) can be used to explain the
      serological specificity of these isolates with C. neoformans factor sera, as was
      previously determined by ELISA in this laboratory. The octasaccharide 1 component
      is the one previously postulated as the structure of the serotype C GXM although
      definitive placement of the beta-Xyl-(1-->4) residues had previously not been
      determined. The heptasaccharide 2 component is uniformly found as the repeating
      unit in the polysaccharide from serotype B isolates. Additionally, GXM 401 was
      found to contain a small amount of the hexasaccharide repeating unit usually
      attributed to serotype A GXM.

PMID- 8542607
TI  - Inhibition of human leukocyte elastase by chemically and naturally oversulfated
      galactosaminoglycans.
AB  - Several samples of oversulfated chondroitin and dermatan were obtained by
      chemical sulfation and by SAX-HPLC enrichment. The starting products and
      oversulfated products were tested as potential inhibitors of human leukocyte
      elastase, an enzyme hypothesized to be involved in the etiology of diseases such
      as emphysema, atherosclerosis, and rheumatoid arthritis. Chemical oversulfation
      (SO3H/COOH 1.6-3.2), preferentially occurring at C-6 of galactosamine residues,
      was found generally to increase the inhibitory power on elastase. Chemically
      oversulfated galactosaminoglycans thus have potential as therapeutic agents,
      considering that they produce non-significant effects on the hemocoagulative
      system. Two naturally oversulfated dermatans sulfate (SO3H/COOH ca. 1.2), mainly
      oversulfated at C-2 of iduronic acid residues, showed comparatively higher
      anticoagulant activity (in the HC-II mediated thrombin inhibition test).

PMID- 8542608
TI  - Molecular and crystal structure of methyl 2,3,4-tri-O-acetyl-beta-D-xylopyranosyl
      (1-->2)-3-O-benzyl-4,6-O-benzyl idene- alpha-D-mannopyranoside.

PMID- 8542609
TI  - Intermolecular aglycon transfer of ethyl 1-thiorhamnopyranosides under Koenigs
      Knorr and Helferich glycosylation conditions.

PMID- 8542610
TI  - Synthesis of curdlan sulfates having inhibitory effects in vitro against AIDS
      viruses HIV-1 and HIV-2.

PMID- 8542611
TI  - The beta-D-GalpNAc-(1-->3)-D-Galp linkage through the oxazoline glycosylation
      method.

PMID- 8542613
TI  - [The refractoriness of heart failure].

PMID- 8542612
TI  - Structural definition of the glycopeptidolipids and the pyruvylated, glycosylated
      acyltrehalose from Mycobacterium butyricum.

PMID- 8542614
TI  - [New criteria for the classification of cardiomyopathies].

PMID- 8542615
TI  - [The coronary circulation, renin-angiotensin system and ACE inhibition].

PMID- 8542616
TI  - Atrial natriuretic peptide and body fluid homeostasis: leading actor or bit-part
      player?

PMID- 8542617
TI  - Treatment of vascular disease with local drug delivery systems.

PMID- 8542618
TI  - [The short- and medium-term ambulatory radionuclide study of left ventricular
      function (VEST) after aortocoronary bypass].
AB  - The aim of the present study was to evaluate the variation in left ventricular
      function at 15 and 120 days after bypass surgery. Ten male patients (mean age
      59.6 +/- 7 years) with previous myocardial infarction and coronary stenosis of at
      least two main vessels, underwent a radionuclide ambulatory monitoring of left
      ventricular function (VEST) during: handgrip test, mental stress test, walking,
      climbing stairs. These tests were carried out 8 +/- 2 days before (T0), 15 +/- 3
      days (T1) and 120 +/- 11 days after coronary bypass; heart rate (HR), ejection
      fraction (EF), stroke volume (SV), and cardiac output (CO) were evaluated beat by
      beat before and during the test until the maximal HR was reached. Handgrip and
      mental stress tests did not induce significant variations in cardiac indices both
      before and after cardiac surgery. No variation in HR was observed before and
      after the test. During walking, at T0, HR increased from rest to maximal effort
      (p < 0.01) with a significant decrease in EF (p < 0.05); at T1 HR, EF, SV and CO
      increased with respect to rest (p < 0.01); AT T2 HR, EF (p < 0.05) and CO (p <
      0.01) increased with respect to rest. Climbing stairs, at T0, HR increased (p <
      0.01) and EF decreased (p < 0.05); at T1 HR, EF, CO (p < 0.05) and SV (p < 0.01)
      increased with respect to rest. At T2 an increase in HR (p < 0.01) and CO (p <
      0.05) was observed at maximal effort with respect to rest. The statistical
      analysis on the percentage variations between baseline and maximal effort
      (climbing stairs) showed a significant increase in SV at T2 compared to T0 (p <
      0.01). In conclusion, VEST during daily normal activities 15 days and 4 months
      after bypass surgery showed a significant increase in cardiac function indices.
      The best results obtained at T1 can be explained with the transient increase in
      adrenergic tone at the time of early postoperative period.

PMID- 8542619
TI  - Activation or block of adenosine triphosphate-sensitive potassium channel have
      opposite effects on postcardioplegic myocardial dysfunction, "stunning". A
      multivariate prediction based on relative operating characteristic curve.
AB  - The relative effects of nicotinic acid (NA) and nitroglycerin (NT) added to cold
      high K+ cardioplegia were studied, to represent the two moieties of the adenosine
      triphosphate-sensitive potassium channel (KATP) activator nicorandil (N). In
      addition, we made a pooled analysis of a large series of experiments performed in
      our Laboratory to investigate the effects of KATP activation by N, or block (by
      glibenclamide, G), on postcardioplegic myocardial dysfunction. In both studies,
      reversibility from myocardial dysfunction (stunning) was assessed by the positive
      inotropic agent dobutamine. Guinea pig papillary muscle preparations were
      immersed in Tyrode's solution (O2 content 16 ml/l, 37 degrees C), then hypoxic
      (O2 content 5 ml/l) superfusion with hypothermic (20 degrees C) cardioplegic
      Saint Thomas' Hospital solution (STHS) was performed for 120 min. We
      investigated: A) 5 groups based on treatments added to STHS: 1) saline (Control
      (C)); 2) N = 1 mmol/L; 3) G = 1 mumol/L (also given for 15 min in Tyrode's
      solution); 4) NA = 1 mmol/L; 5) NT = 100 mumol/L; B) 76 consecutive experiments
      and we defined, independent of whether just before or during STHS: 1) KATP
      activation (by N, in the concentration range 1 mumol/L to 1 mmol/L, n = 36); 2)
      KATP block (by G 1 mumol/L, either alone or just before N, n = 20); 3) controls
      (n = 20) (either saline, n = 12, or saline plus dimethyl sulfoxide, as vehicle,
      at the ratio 100 to 1, n = 8). Absolute isometric contractility variables were
      evaluated along with percent changes of baseline values: 1) at 30 s of STHS, 2)
      after 60 min of reoxygenation with Tyrode's solution and 3) following further 15
      min of dobutamine 10 mumol/L. In all preparations, developed tension (DT), time
      to peak tension (TPT), DT/TPT and time to arrest (TTA) were measured. In study
      A): TTA was significantly abbreviated (intergroup F = 5.79, p < 0.001) in N (49
      +/- 11 s, mean +/- SD) p < 0.01 vs C and NA). At 30 s of STHS %DT/TPT was
      unchanged among groups. By contrast, after 60 min of reoxygenation %DT/TPT in N
      (118 +/- 35%, p < 0.05 vs C, p < 0.01 vs G) was improved (intergroup F = 5.48, p
      < 0.002). G, NA and NT showed recovery of contractility similar to C. However,
      after dobutamine the poorest %DT/TPT were seen in G (p < 0.01 vs C, p < 0.05 vs
      N). In study B): using the multivariate logistic model, with KATP activation, the
      odds of normal contractile response, respectively at 60 min of reoxygenation (t =
      2.81) and after dobutamine (t = 3.22), were 29.8 and 8.86 of controls, whereas
      TTA (t = -1.59) was inversely related. Moreover, with KATP block the odds after
      dobutamine was 0.204 of controls. The relative operating characteristic plots
      showed areas under the curve greater than 0.7, which is evidence for accurate
      assessment of the predictive rules adopted. This is the first report where a
      probabilistic approach to cardioplegia-related experiments showed high accuracy
      in predicting the recovery of post-hypoxic contractile function (stunning). The
      results indicate that on postcardioplegic stunning: 1) KATP activation by N and
      KATP block by G (both given prior to or contemporary with hypoxia) have opposite
      effects; 2) the favorable effects of nicorandil seem unrelated to its
      nicotinamide or nitrose moieties.

PMID- 8542620
TI  - Risk factors in patients with different clinical and angiographic manifestations
      of ischemic heart disease.
AB  - In patients who present with unheralded myocardial infarction both the severity
      and the extent of coronary atherosclerosis appear to be less than that in
      patients with chronic stable angina, thus suggesting that, in the latter,
      protective factors may prevent or delay the evolution towards acute coronary
      syndromes. Therefore, risk factors were compared in 88 consecutive patients (73
      men; mean age 56 +/- 9 years) with unheralded myocardial infarction and a single,
      discrete, > 70% stenosis in the proximal right, left circumflex or left anterior
      descending coronary artery (Group 1) and in 55 consecutive patients (46 men; mean
      age 58 +/- 9 years with chronic stable angina and multiple, diffuse, > 70%
      stenoses localized both in the right and left coronary arteries (Group 2).
      Continuous data are presented as mean value +/- 1 SD, proportions as percentages.
      In Group 1 mean serum levels of total cholesterol, low-density lipoprotein
      cholesterol and triglycerides were similar to those in mg/dl, p = 0.93 and 160 +/
      87 vs 155 +/- 76, p = 0.74, respectively) while the mean serum level of high
      density lipoprotein cholesterol was higher in Group 2 (49 +/- 4 vs 46 +/- 4
      mg/dl, p = 0.005). The prevalence of a positive family history of ischemic heart
      disease, hypertension and smoking habit were similar in the two groups, while the
      prevalence of diabetes mellitus was higher in Group 2 (29 vs 6%, p = 0.001).
      Thus, in patients with otherwise similar coronary risk factors, higher levels of
      high-density lipoprotein cholesterol and diabetes mellitus appear to be
      associated with a reduced tendency of coronary atherosclerosis to cause acute
      coronary syndromes.

PMID- 8542621
TI  - [Loculated pericardial effusion leading to functional tricuspid stenosis in a
      case of rheumatoid arthritis].
AB  - We describe a case of loculated pericardial effusion, occurring in a women
      affected by rheumatoid arthritis. Because of its peculiar location, close to the
      atrioventricular plane, the effusion caused a haemodynamic pattern resembling
      tricuspid valve stenosis.

PMID- 8542622
TI  - [The organizational aspects of a cardiological rehabilitation center].

PMID- 8542623
TI  - [Coronary endovascular prostheses (stents)].

PMID- 8542624
TI  - Predictors of short term clinical and angiographic outcome after coronary
      angioplasty for acute myocardial infarction.
AB  - Coronary angioplasty is an effective method to achieve myocardial reperfusion in
      acute myocardial infarction (AMI). We reviewed our experience in 132 patients
      (pts) who underwent percutaneous transluminal coronary angioplasty (PTCA) of a
      totally occluded infarct-related artery (IRA) within 24 h after the onset of
      symptoms (mean delay 10 +/- 7 h), in order to identify the predictors of primary
      success and of major complications. PTCA was successfully performed in 113
      patients (86%). Failure without complications occurred in 12 patients (8.4%);
      untoward events (death and emergency CABG) occurred in seven patients (5.3%). Pts
      in the failure group were more likely to have cardiogenic shock (53 vs. 8.8%, P <
      .0005), longer time to reperfusion (15 +/- 6 vs. 9 +/- 6 h, P < .0005), lower
      ejection fraction (EF) (42 +/- 16 vs. 54 +/- 12%, P < .0005), multivessel disease
      (74 vs. 43%, P < .03), and a smaller IRA diameter (2.8 +/- 0.6 vs. 3.1 +/- 0.6
      mm, P < .03). Sex, age, previous bypass surgery, previous thrombolytic treatment,
      IRA, and infarct location were similar in both groups. Absence of cardiogenic
      shock (P < .0001), decreasing time to reperfusion (P < .005) and increasing EF (P
      < .02) were independent predictors of successful PTCA. Presence of cardiogenic
      shock (P < .0001) and decreasing EF (< .05) were independent predictors of
      untoward events. Repeat angiography was performed 24 h after the procedure in the
      success group. Angiographic deterioration (stenosis > or = 50% and/or TIMI flow
      grade < or = 1) was present in 18 pts (16%), among whose 5 pts (4.4%) had re
      occlusion of the IRA. Pts with early angiographic deterioration were more likely
      to have a lower IRA diameter (2.8 +/- 0.5 vs. 3.1 +/- 0.6 mm, P < .02).
      CONCLUSION: Emergency PTCA is an effective method for establishing reperfusion in
      AMI. Pts with high-risk baseline characteristics show the highest rate of
      untoward events, but are the most likely to benefit from aggressive reperfusion
      therapy.

PMID- 8542625
TI  - Angioplasty therapy of acute myocardial infarction in the real world.

PMID- 8542626
TI  - Balloon mitral valvotomy in patients with systemic and suprasystemic pulmonary
      artery pressures.
AB  - Mitral stenosis with severe pulmonary artery hypertension constitutes a high risk
      subset for surgical commissurotomy or valve replacement. Balloon mitral valvotomy
      has been proposed as a technique for treating high risk surgical patients with
      mitral stenosis. The efficacy of this technique in patients with severe pulmonary
      artery hypertension, however, has not been fully evaluated. Percutaneous
      transvenous mitral commissurotomy (PTMC) was performed in 450 consecutive
      patients. Of these, forty-five (10%) patients had systemic or suprasystemic
      systolic pulmonary artery pressures (110 +/- 20, range 96 to 170 mm Hg). The
      baseline characteristics and immediate hemodynamic results of these 45 patients
      with systemic/suprasystemic systolic pulmonary artery pressures (group I) were
      analysed and compared with those of 405 patients with subsystemic systolic
      pulmonary artery pressures (group II). Patients in group I were more symptomatic
      (New York Heart Association functional class > or = III, 96 vs. 55%, P < 0.001)
      and had severe subvalvular fibrosis (mitral subvalvular distance ratio [MSDR],
      0.14 +/- 0.04 vs. 0.22 +/- 0.04, P < 0.01). Before PTMC, mean transmitral
      gradient was higher (34 +/- 8 vs. 25 +/- 4 mm Hg, P < 0.02) and mitral valve area
      smaller (0.5 +/- 0.3 vs. 0.9 +/- 0.4 cm2, P < 0.02) in group I patients, who also
      had higher pulmonary vascular resistance (16 +/- 5 vs. 9 +/- 5 U, P < 0.005).
      After PTMC final mean transmitral gradients (7 +/- 3 vs. 5 +/- 3 mm Hg) and
      mitral valve areas (1.9 +/- 0.4 vs. 2.0 +/- 0.4 cm2) were similar in both groups
      (P = NS). Group I patients had a greater decrease in pulmonary artery pressures
      (34 +/- 4 vs. 25 +/- 2%, P < 0.05) but final systolic pulmonary artery pressures
      (82 +/- 20 vs. 50 +/- 14 mm Hg) and pulmonary vascular resistance (12 +/- 4 vs. 6
      +/- 4 U) remained significantly higher in this group (P < 0.005). Thus, in
      patients with severe pulmonary artery hypertension, PTMC is a safe and effective
      technique providing good immediate hemodynamic results.

PMID- 8542627
TI  - Primary angioplasty using a urokinase-coated hydrogel balloon in acute myocardial
      infarction during pregnancy.
AB  - A 38-year-old multigravid white female presented at 16 weeks gestation with an
      acute inferoposterolateral myocardial infarction. Emergent coronary angiography
      demonstrated a total proximal occlusion of a large dominant left circumflex
      artery with a filling defect at the site of the occlusion suggestive of thrombus.
      Primary angioplasty using a urokinase-coated hydrogel balloon resulted in
      successful recanalization of the vessel with restoration of normal TIMI Grade III
      flow and, most notably, apparent complete lysis of the intracoronary thrombus.
      After a subsequently uneventful pregnancy, a healthy baby was delivered.

PMID- 8542628
TI  - Long-term effects of balloon coarctation angioplasty on arterial blood pressure
      in adolescent and adult patients.
AB  - In patients with coarctation of the aorta arterial hypertension frequently
      persists when surgical repair is performed after age 20 years. There are little
      data on the long-term effect of angioplasty and the question remains to be
      determined whether hypertension is sufficiently treated by this procedure. Twenty
      nine consecutive patients (9 females and 20 males) 14 to 54 years old (median,
      25) underwent angioplasty for native coarctation of the aorta. Twenty-five
      patients (86%) had pre-existing systolic arterial hypertension (> 140 mm Hg). The
      mean peak systolic pressure gradient decreased from 62 +/- 18 to 21 +/- 13 mm Hg
      immediately after angioplasty. At hospital discharge 13 patients still had
      hypertension. After a mean follow-up interval of 4.0 years (range, 0.3-9.5) the
      residual peak pressure gradient was 14 +/- 13 mm Hg. Blood pressure was normal
      without antihypertensive therapy in 23 patients (79%). In the six hypertensive
      patients the pressure gradients were 7, 13, 30, 30, 35, and 60 mm Hg. One patient
      died 8 months after angioplasty and another underwent surgery for aortic
      aneurysm. Although this was an uncontrolled study the data suggest that
      normalization of blood pressure may occur more frequently after angioplasty than
      after surgery in adolescents and adults with native coarctation.

PMID- 8542629
TI  - Late development of dissecting aneurysm following balloon angioplasty of native
      aortic coarctation.
AB  - Acute aortic dissection during balloon angioplasty for coarctation of the aorta
      or aneurysm formation during follow-up are well-known complications of this
      procedure. Dissecting aneurysm development during long-term follow-up after
      balloon angioplasty of a native coarctation has not been previously reported. We
      report a case in which a huge dissecting aneurysm developed 3 years after the
      native coarctation angioplasty procedure. The aneurysm required surgical repair.

PMID- 8542630
TI  - Aneurysm associated with balloon angioplasty of aortic coarctation: future
      prevention and treatment.

PMID- 8542631
TI  - Transcatheter closure of large atrial septal defects with the Babic system.
AB  - An improved 10 Fr version of the atrial septal defect (ASD) occlusion system
      consisting of two umbrellas for transvenous introduction over the long veno
      arterial guide-wire was used to attempt closure in five adult patients with large
      defects (26-35 mm). The umbrellas are made of nitinol wire frame and a thin
      membrane of microporous polyurethane. Supported by the metal cannula and guided
      by selective left atriography, the umbrellas of 45-60 mm were placed individually
      into the atria and screwed together at the septum level by means of a torquer
      catheter. Positioning and screwing on, unscrewing, separating, and repositioning
      the umbrellas up to 17 times were needed to anchor the prosthesis correctly in a
      patient. The prosthesis could be implanted primarily in all patients (in one at
      second session). Dislodgement of a 60 mm prosthesis and left atrial perforation
      with a 55 mm prosthesis required surgery in two patients 8 hours and 2 weeks post
      procedure, respectively. A single umbrella-arm fracture was noticed in one
      patient 4 months after the implantation. All five patients were free of symptoms
      at follow-up after 7-10 months. Transcatheter closure of large ASDs is
      technically feasible with this system. The morbidity is mainly associated with
      the implantation of very large umbrellas.

PMID- 8542632
TI  - Transcatheter closure of large atrial septal defects: good try--challenging works
      ahead.

PMID- 8542633
TI  - Transcatheter closure of residual atrial septal defect following implantation of
      buttoned device.
AB  - We report a case in which residual shunting after a buttoned device occlusion of
      atrial septal defect (ASD) was eliminated by transcatheter retrieval of a portion
      of the device, followed by implantation of a second device. This method may be
      helpful for those patients with residual ASDs who decline surgical device
      retrieval and defect closure.

PMID- 8542634
TI  - Orthodeoxia-platypnea due to intracardiac shunting--relief with transcatheter
      double umbrella closure.
AB  - The safety and efficacy of transcatheter clamshell occlusion of patent foramen
      ovale for relief of severe arterial desaturation and dyspnea in the upright
      position due to intracardiac shunting were examined in eight patients with
      excessive risk of surgical patent foramen ovale closure. All patients had
      successful reduction of intracardiac shunting with an immediate rise in oxygen
      saturation > or = 95% by implantation of a clamshell device on the atrial septum.
      Despite two early incidents of device embolization, retrieval and immediate re
      implantation, and one patient with nonsustained atrial and ventricular
      arrhythmias, there were no adverse clinical sequelae. In follow-up evaluation
      transcatheter clamshell closure of patent foramen ovale has provided persistent
      relief from shunt-related arterial desaturation and symptomatology in all living
      patients.

PMID- 8542635
TI  - Transcatheter closure of oversized persistent ductus arteriosus by simultaneous
      delivery of two Rashkind umbrella devices.
AB  - Transcatheter closure of persistent ductus arteriosus (PDA) with a diameter of >
      9 mm is considered to be impossible or at least difficult with the occlusion
      systems that are currently available. We report a simple technique for occluding
      oversized PDAs with two diameter of 13 mm was successfully occluded in a 40-year
      old man. Complete closure without residual shunt was documented by echocardiogram
      and angiogram.

PMID- 8542636
TI  - Transcatheter closure of residual patent ductus arteriosus shunting after the
      Rashkind occluder device using single or multiple Gianturco coils.
AB  - Transcatheter closure of a patent ductus arteriosus (PDA) using the Rashkind
      occluder or the buttoned device is accompanied with a 7-38% incidence of residual
      shunt. Closure of the residual shunt with a second device is expensive,
      associated with possible morbidity, can be technically challenging, and
      occasionally does not completely eliminate the shunt. Our objective was to assess
      the immediate and short-term results of transcatheter closure of residual PDA
      after the Rashkind device using single or multiple Gianturco coils. Five patients
      (one male/four female) underwent transcatheter closure of residual PDA at a
      median age of 8.4 yr (range 2-10.1 yr) and median weight of 23 kg (range 11.8-32
      kg). A 4F catheter was used for delivery of the coils in all patients. Three
      patients underwent multiple coil and two single coil closure with complete
      elimination of the shunt. There was complete elimination of the shunt as
      documented by repeat angiography immediately after the coil closure. The median
      fluoroscopy time was 24 min (range, 22-55 min). All patients were discharged home
      on the same day. There were no complications Follow-up evaluation was performed
      with color flow mapping of the main pulmonary artery within 4 hr after closure
      and 6 weeks later with echocardiography and chest radiography. We conclude that
      transcatheter closure is an effective therapy for patients with residual PDA
      after the Rashkind device using the single or multiple coil technique. This
      technique can be performed on an out-patient basis without the need for general
      anesthesia and at a lower expense than a repeat occluder device or surgery.

PMID- 8542637
TI  - Stenting for pulmonary artery stenosis following the Ross procedure.
AB  - A 34-year-old woman showed the development of significant main pulmonary artery
      obstruction along the supravalvar suture line 18 months following a Ross
      procedure. The patient underwent unsuccessful balloon angioplasty, followed by
      successful stent implantation. The angiographic narrowing disappeared
      postprocedure, and the excellent hemodynamic result maintained at 4 month follow
      up.

PMID- 8542638
TI  - Pressure recordings in coexistent fixed congenital membraneous and hypertrophic
      subaortic stenosis.

PMID- 8542639
TI  - Percutaneous retrieval of a broken umbilical catheter from left atrium in a
      premature newborn.
AB  - A 30-week gestational age baby boy weighing 1,117 g born with cesarian section
      had a broken umbilical vein catheter lodged in the left superior pulmonary vein.
      We successfully retrieved the foreign body by percutaneous approach using a
      pigtail catheter and a snare wire under portable fluoroscopy.

PMID- 8542640
TI  - Use of a snare-loop device as an adjunct to Palmaz stent placement.
AB  - A patient was treated by PTA for a tight excentric stenosis in the external iliac
      artery. Following angioplasty, appropriate placement of a Palmaz stent over the
      lesion was impossible because of arterial curves and irregular aspect of the
      residual stenosis. To overcome this problem, the stent was grasped and pulled
      over the lesion using a snare loop device by contralateral approach.

PMID- 8542641
TI  - Influence of adjunctive balloon angioplasty on coronary blood flow after
      rotational atherectomy.
AB  - Rotational atherectomy is being performed with increasing frequency in a distinct
      subset of patients whose lesion characteristics are unfavorable for conventional
      balloon angioplasty. Although satisfactory luminal enlargement can be
      accomplished with the use of rotational atherectomy alone in some patients,
      adjunctive balloon angioplasty is necessary in most patients, to obtain a minimal
      residual angiographic result. To demonstrate responses associated with rotational
      atherectomy results, serial coronary blood flow measurements were obtained in a
      patient undergoing rotational atherectomy for unstable angina. Adjunctive balloon
      angioplasty resulted in normalization of post-stenotic coronary flow reserve.
      Recanalization by rotablator alone may not normalize coronary flow despite a
      satisfactory angiographic result.

PMID- 8542642
TI  - Coronary rotablation and reserve: can they occur together?

PMID- 8542643
TI  - Can coronary flow parameters after stent placement predict restenosis?
AB  - Intracoronary stent was used to treat a dissection resulting from balloon
      angioplasty. Coronary flow parameters measured with Doppler Flowire pre- and post
      stenting suggested abnormal coronary flow even after stenting. The patient
      returned 4 months later with an instent restenosis. This case suggests the
      intriguing possibility of coronary flow parameters obtained immediately after new
      device angioplasty in predicting restenosis.

PMID- 8542644
TI  - Clinical significance of an abnormal coronary flow reserve.

PMID- 8542645
TI  - Concurrent balloon dilatation of rheumatic trivalvular stenosis.
AB  - A 26-year-old male presented with increasing dyspnoea and exertional palpitations
      of 2 months duration. The clinical and echo evaluation revealed severe stenosis
      of the mitral, aortic, and tricuspid valves. Concurrent percutaneous dilatation
      of all three valves was done as a single stage procedure. The procedure was
      successful and produced significant clinical and haemodynamic improvement. The
      mitral and tricuspid valves were dilated using the same Inoue balloon, whereas
      the aortic stenosis was dilated using the pigtail tipped balloon.

PMID- 8542646
TI  - Triple valvuloplasties.

PMID- 8542647
TI  - Transcatheter embolization coil closure of patent ductus arteriosus--modified
      delivery for enhanced control during coil positioning.
AB  - The use of Gianturco coils (Cook, Inc., Bloomington, IN) has been recently
      described as a method of occluding restrictive patent ductus arteriosus (PDA).
      Precise control of the coil during positioning or withdrawal is difficult. We
      designed an inexpensive and readily available system to control the coil during
      delivery and repositioning. A 5 French Mallincrodt vertebral catheter was heat
      tapered to allow slight, but definite resistance of a 0.035" guide wire when it
      was passed through the catheter. The delivery system has been used to
      successfully coil occlude restrictive PDAs in seven patients. The system has
      added no additional costs to the procedure and has provided improved control of
      the coil position prior to release of the coil.

PMID- 8542648
TI  - Percutaneous balloon mitral valvuloplasty by the retrograde (Babic) technique in
      a patient with inferior vena cava stenosis.

PMID- 8542649
TI  - Daily variation of serum lipids in relation to the circadian rhythm of platelet
      aggregation in healthy male persons.
AB  - The circadian rhythm of platelet aggregation was compared with that of serum
      lipids in seven healthy male persons. Daily variations of remnant lipoprotein
      cholesterol and of remnant lipoprotein-triglycerides were related to those of
      arachidonic acid-, ADP (adenosine diphosphate)-, and collagen-induced aggregation
      in platelet-rich plasma and to ADP-induced aggregation in whole blood,
      respectively. Statistical analyses indicate that the time course of remnant
      cholesterol was correlated to that of ADP-induced aggregation in platelet-rich
      plasma and the time courses of blood cholesterol and triglyceride were correlated
      to arachidonic acid- and serotonin-induced platelet aggregation in platelet-rich
      plasma, respectively. In whole blood, the time course of remnant lipoprotein
      triglyceride was correlated only to ADP-induced platelet aggregation. In
      contrast, the daily variation of HDL (high density lipoprotein)-cholesterol did
      not influence either that of platelet aggregation in platelet-rich plasma or that
      in whole blood. Our findings are of clinical interest regarding the development
      of atherosclerosis and thrombotic events in persons with an elevated level of
      serum lipids.

PMID- 8542650
TI  - New aspects concerning the regulation of the post-operative acute phase reaction
      during cardiac surgery.
AB  - During a cardio-pulmonary bypass, as well as post-operatively, high levels of
      endotoxin, interleukin-6 (Il-6) and C-reactive protein (CRP) were measured in 30
      patients. A significant increase in endotoxin plasma level occurred during
      surgery, culminating in a peak during reperfusion. Plasma levels of endotoxin
      continued to be slightly raised until the fifth day after surgery, whereas those
      of Il-6 rose at the time the operation came to an end and were at their highest 6
      h later. CRP levels were also high, post-operatively, and were markedly raised on
      day 2. A definite, statistically significant correlation between the plasma
      levels of endotoxin and Il-6 during the operation was established, leading us to
      conclude that the endotoxin liberated during cardiac surgery acts as the main
      trigger in the release of Il-6 and thus induces the post-operative acute phase
      reaction. There was no evidence of a correlation between CRP and endotoxin or Il
      6 plasma levels.

PMID- 8542651
TI  - Enhanced susceptibility of low-density lipoprotein to in vitro oxidation in type
      1 and type 2 diabetic patients.
AB  - Macrovascular disease represents a major cause of morbidity and mortality in
      patients with diabetes mellitus. Low-density lipoprotein (LDL) is involved in the
      pathogenesis of atherosclerotic lesions, through modifying processes such as
      oxidation. We examined the in vitro susceptibility to oxidation and the
      oxidizability of LDL isolated from the plasma of Type 1 and Type 2 diabetic
      patients. Two groups of diabetic patients (20 Type 1, 20 Type 2) were compared
      with sex- and age-matched non-diabetic control groups. In vitro oxidation of the
      purified LDL preparations was assessed by determination of the kinetics for the
      formation of conjugated dienes (lag phase duration, maximal rate and maximal
      dienes concentration) and by measurement of thiobarbituric acid-reacting
      substances (TBARS) in the presence of copper ions. LDL from both Type 1 and Type
      2 diabetic patients exhibited a shorter lag phase duration for conjugated dienes
      formation (94 +/- 14 vs. 108 +/- 20 and 97 +/- 26 vs. 112 +/- 18 min for Type 1
      and Type 2 diabetic groups vs. respective control groups, P < 0.05). We also
      observed an increase in maximal rate of conjugated dienes formation (2.21 +/-
      0.55 vs. 1.52 +/- 0.31 and 2.02 +/- 0.55 vs. 1.52 +/- 0.31 nmol/mg LDL/min, P <
      0.01) and of maximal production of TBARS (77.9 +/- 11.8 vs. 65.5 +/- 10.4 and
      76.7 +/- 9.9 vs. 65.3 +/- 9.4 nmol/mg LDL protein, P < 0.05) in diabetic groups.
      Our results demonstrate both a higher susceptibility to oxidation and a higher
      oxidizability of LDL from diabetic patients, as much for Type 1 as Type 2
      diabetic subjects with or without pre-existent vascular complications. This
      enhanced propensity of LDL oxidation in patients with diabetes mellitus could at
      least partly be attributable to quantitative and qualitative alterations in the
      chemical composition of LDL and to the glycoxidation process occurring on these
      lipoproteins.

PMID- 8542652
TI  - Comparison between serum levels of bone alkaline phosphatase and the carboxy
      terminal propeptide of type I procollagen as markers of bone formation in
      patients following renal transplantation.
AB  - The serum concentrations of the carboxy-terminal propeptide of type I procollagen
      (PICP) were monitored in 52 serum samples from 13 patients receiving renal
      transplants and the values compared with bone alkaline phosphatase (BAP)
      concentrations and intact parathyrin levels. There was a significant correlation
      between BAP and PICP values in all 52 serum samples examined (r = +0.770; P <
      0.0001). Before transplantation BAP (P < 0.0001), but not PICP (P > 0.1), was
      correlated with intact parathyrin levels. BAP concentrations increased from 7.3
      +/- 1.2 micrograms/l (median +/- S.E.M.) before transplantation to 13.3 +/- 1.2
      micrograms/l 3 months after transplantation (P < 0.01). There was a concomitant
      rise in PICP levels from 95 +/- 19 micrograms/l to 166 +/- 27 micrograms/l (P <
      0.05). No correlation was found between BAP or PICP levels on the one hand and
      intact parathyrin concentrations on the other at any time following renal
      transplantation (P > 0.5). In conclusion, PICP may be a useful parameter for
      monitoring bone formation following renal transplantation.

PMID- 8542653
TI  - Bi-enzyme reactor for electrochemical detection of low concentrations of uric
      acid and glucose.
AB  - An enzyme-based flow-injection amperometric analysis system (FIA) for monitoring
      of uric acid and glucose is described. The oxidase and peroxidase enzymes are
      physically coimmobilised in a sandwich-type reactor and ferrocene serves as a
      mediator. The assays are based on the measurement of a reduction current
      resulting from the enzymatic reactions, at a glassy carbon electrode held at 0.00
      mV (vs. Ag/AgCl). The high selectivity (ascorbic acid did not interfere) is
      coupled to high sensitivity (a detection limit of 30 and 60 nmol/l for uric acid
      and glucose, respectively; signal/noise = 3) and good stability (the enzymes
      remained active for more than 6 weeks at 30 degrees C). The usefulness of the
      assay in clinical chemistry is illustrated by the measurement of human serum uric
      acid and glucose concentration. The results obtained were in fairly good
      agreement with those obtained using conventional hospital laboratory methods.

PMID- 8542654
TI  - Solid-phase competitive luminescence immunoassay for lysozyme in faeces.
AB  - We have developed a new simple solid-phase luminescence immunoassay (LIA) for the
      determination of faecal lysozyme. The assay utilises a polyclonal capture
      antibody coated to polystyrene beads and acridinium ester-labelled human lysozyme
      as tracer. Samples are incubated with polystyrene beads and tracer overnight at 4
      degrees C. After a thorough washing step, emitted light is measured by an
      automated luminometer for 2 seconds. The standard curve uses five standards
      ranging from 0.025 to 6.4 mg/l. The method has a sensitivity of 0.02 mg/l.
      Dilution recoveries for three samples were 88, 104 and 108%. Intraassay
      coefficients of variation (CV, n = 24) were 10.1% and 11.7% for a healthy control
      and a patient sample; interassay CV (n = 16) were 6.7% and 13.1% for the same
      healthy control but another patient sample. The normal range of faecal lysozyme
      in 80 healthy controls was found to be 0.02-1 mg/l (97.5 percentile) with a
      median of 0.28 mg/l. Fifty-three patients with Crohn's disease had faecal
      lysozyme values ranging from 0.16 to 100.7 mg/l with a median of 1.75 mg/l, and
      30 patients with ulcerative colitis showed levels between 0.09 and 118 mg/l with
      a median of 1.11 mg/l. The assay has proved useful for differentiating healthy
      individuals from those with inflammatory bowel disease and might be a valuable
      tool for diagnosing or evaluating inflammatory bowel disease.

PMID- 8542655
TI  - Osteocalcin metabolism in late fetal life: fetal and maternal osteocalcin levels.
AB  - To clarify the osteocalcin metabolism in the fetus, we determined venous
      osteocalcin levels of 13 women and umbilical arterial and venous osteocalcin
      levels of their newborns at delivery. Calcium, phosphorus and alkaline
      phosphatase levels were also established. Umbilical arterial and venous blood
      calcium and phosphorus levels were significantly higher than maternal venous
      blood values (P < 0.001 for all). Umbilical arterial calcium was 2.46 +/- 0.02
      mmol/l, phosphorus 1.48 +/- 0.04 mmol/l, umbilical venous calcium 2.50 +/- 0.03
      mmol/l, phosphorus 1.45 +/- 0.04 mmol/l, maternal calcium 2.16 +/- 0.03 mmol/l,
      phosphorus 0.98 +/- 0.04 mmol/l. Both umbilical venous (5.85 +/- 0.66 nmol/l) and
      arterial (3.49 +/- 0.51 nmol/l) osteocalcin levels were significantly higher than
      maternal values (1.42 +/- 0.15 nmol/l). The high umbilical venous osteocalcin
      levels may be due to increased osteocalcin degradation in fetus or placental
      osteocalcin synthesis.

PMID- 8542656
TI  - The effect of ascorbic acid on the measurement of total cholesterol and
      triglycerides: possible artefactual lowering in individuals with high plasma
      concentration of ascorbic acid.

PMID- 8542657
TI  - Phenotyping of glutathione S-transferase M1 in the Estonian population by ELISA
      using GSTM1a and GSTM1b specific monoclonal antibodies.

PMID- 8542658
TI  - Creatine kinase isoenzymes in human trichinellosis.

PMID- 8542659
TI  - The rank correlation coefficient: an additional aid in the interpretation of
      laboratory data.

PMID- 8542660
TI  - Marked decrease of plasma apolipoprotein AI and AII in Japanese patients with
      late-onset non-familial Alzheimer's disease.

PMID- 8542661
TI  - Pulmonary surfactant protein A: a serum marker of pulmonary fibrosis in patients
      with collagen vascular diseases.

PMID- 8542662
TI  - Liver biopsy: review of methodology and complications.
AB  - Liver biopsy remains an essential tool to confirm a suspected diagnosis and guide
      specific therapy in patients with liver disease. The methods available to obtain
      liver tissue include percutaneous needle biopsy, transjugular biopsy, image
      guided needle biopsy, and laparoscopic direct vision guided needle biopsy.
      Advantages and disadvantages of each modality are reviewed herein. The
      indications for liver biopsy include evaluation of elevated aminotransferases,
      assessment of response to therapy of chronic liver disease, monitoring for
      hepatoxicity of drug therapy, and liver transplant allograft evaluation.
      Contraindications include impaired coagulation, significant ascites, high-grade
      extrahepatic biliary obstruction, echinococcal cyst, and certain anatomic
      abnormalities. Complications include pain, hemorrhage, bile peritonitis,
      penetration of abdominal viscera, pneumothorax, and death. Complications are
      reported in 0.06-0.32% of the patients. Death as a direct result of liver biopsy
      is extremely rare (0.009-0.12%). In properly selected patients, liver biopsy has
      a high benefit/risk ratio and is often considered the final and definitive
      diagnostic test.

PMID- 8542664
TI  - Diabetic gastroparesis.
AB  - Diabetic gastroparesis is a common, underrecognized disorder affecting both type
      I and type II diabetics usually in the setting of other diabetic complications.
      The pathogenesis of diabetic gastroparesis is poorly understood, but autonomic
      neuropathy appears to play a major role. The symptoms of gastroparesis are
      nonspecific, and complications such as hypoglycemia and bezoar formation due to
      gastric stasis may occur. Diabetic gastroparesis can be assessed by measuring the
      gastric emptying of solid radiopaque markers or by scintigraphy. Treatment
      approaches include optimizing glycemic control and the use of prokinetic agents.
      Combination therapy or the alternating use of prokinetic agents may prove to be
      beneficial in dealing with drug tachyphylaxis.

PMID- 8542663
TI  - Clinical significance of gastric myoelectrical dysrhythmias.
AB  - Normal rhythmic myoelectrical activity of the human stomach is 3 cpm, regulating
      gastric contractile activity. Dysrhythmia in gastric myoelectrical activity is
      found to be associated with functional disorders of the stomach. Gastric
      dysrhythmias are classified into tachygastria (frequency higher than normal),
      bradygastria (frequency lower than normal) and arrhythmia (no rhythmic activity).
      Clinical significance of gastric dysrhythmias is discussed in this paper,
      outlined as follows: (a) What is normal gastric myoelectrical activity and what
      is dysrhythmia? (b) How to detect gastric dysrhythmias? (c) Gastric dysrhythmias
      in clinical settings. (d) What may cause gastric dysrhythmias? (e) How to
      normalize gastric dysrhythmias?

PMID- 8542665
TI  - Are collagenous colitis and lymphocytic colitis distinct syndromes?
AB  - The term microscopic colitis has largely evolved to be an umbrella term which
      includes the histopathological entities of lymphocytic colitis and collagenous
      colitis. The purpose of this review is to compare these two syndromes.
      Lymphocytic colitis and collagenous colitis are characterized by chronic watery
      diarrhea, normal radiographic and endoscopic findings, and abnormal colonic
      mucosa on biopsy with lymphocytic infiltration of the lamina propria but minimal
      crypt distortion. Collagenous colitis is further characterized by a thickened
      subepithelial collagen band. Lymphocytic colitis has an equal sex distribution,
      while collagenous colitis has a marked female predominance. Histocompatibility
      phenotypes are also dissimilar. These findings suggest that lymphocytic colitis
      and collagenous colitis may be related but distinct syndromes.

PMID- 8542666
TI  - Bile acid malabsorption: mechanisms and treatment.
AB  - Bile acid malabsorption is often due to a disease or partial resection of the
      terminal ileum and more rarely a genetic defect in the distal ileum. It is often
      associated with diarrhoea with or without steatorrhoea, and it may be complicated
      by gallstone disease and hyperoxaluria. Bile acid malabsorption is rather easily
      diagnosed using the selenohomocholic acid taurine test. Patients with bile acid
      induced diarrhoea should be recommended a low-fat diet. Cholestyramine may be
      recommended in moderate bile acid diarrhoea. In patients with more severe bile
      acid malabsorption, cholylsarcosine may be used as a replacement therapy.

PMID- 8542667
TI  - Adhesion molecules in inflammatory and neoplastic intestinal diseases.
AB  - Adhesion molecules participate in a broad variety of biological processes, i.e.
      tumor progression and inflammation, through their involvement in cell-to-cell
      interactions and immunoinflammatory cell migration. This review describes the
      basic properties of adhesion molecules with reference to inflammatory bowel
      disease and colorectal carcinoma. Accumulating data suggest that adhesion
      molecules could be pathogenetically pertinent to other gastrointestinal disorders
      such as celiac disease (nontropical sprue) and gastroduodenal ulcer. Future
      therapeutic approaches in inflammatory and malignant disorders may possibly be
      development of principles targeting adhesion molecules.

PMID- 8542668
TI  - Modulation of vasoconstriction by endothelium-derived nitric oxide: the influence
      of vascular disease.
AB  - 1. The endothelium makes a significant contribution to the regulation of vascular
      tone through the release of potent vasodilator agents such as nitric oxide (NO)
      and prostacyclin (PGI2) as well as vasoconstrictor compounds such as endothelin.
      Recognition of this function of the endothelium has created a new focus for the
      investigation of vasoconstrictor activity under physiological and pathological
      conditions. 2. It has been well established that removal of the endothelium
      enhances responses to a variety of contractile agents in conductance arteries and
      that such modulation is predominantly due to the release of NO. The use of
      selective inhibitors of NO synthesis has confirmed that the endothelium-derived
      nitric oxide also modulates constriction in resistance vessels. 3. In a number of
      cardiovascular disease states there is impairment of endothelial function. Thus
      one of the consequences of atherosclerosis, hypertension and ischaemia is a
      reduction in endothelium-dependent vasodilatation, both at a basal level and in
      response to endogenous and exogenous stimuli. In addition, enhanced responses to
      vasoconstrictors have been reported in those disease states. Such observations
      have led to the attractive hypothesis that enhanced constriction in vascular
      disease results from attenuate NO-induced dilatation. However, whilst there is
      some evidence that pathological impairment of endothelial function is accompanied
      by increased constrictor activity, particularly where serotonergic mechanisms are
      involved, it is inappropriate to make the general assumption that where disease
      impairs NO activity there will also be increased sensitivity to all constrictor
      stimuli.

PMID- 8542669
TI  - Good vibrations? Respiratory rhythms in the central control of blood pressure.
AB  - 1. Arterial blood pressure is maintained, and reflexly controlled, by the
      activity of neurons in the medulla and spinal cord. 2. Rhythmic, automatic,
      respiratory activity is generated by neurons in the ventral medulla and
      transmitted to premotoneurons and motoneurons in the medulla and spinal cord. 3.
      Sympathetic nerve activity often has a respiratory rhythmicity. 4. One site at
      which the interaction between respiratory and sympathetic neurons occurs is the
      ventrolateral medulla. 5. Different types of sympathetic neurons, such as muscle
      vasoconstrictor, sudomotor and pilo-erector, have different patterns of
      respiratory rhythmicity. 6. Inputs from medullary respiratory neurons to
      medullary sympathetic premotor neurons may be the mechanism that co-ordinates the
      activity of these two vital systems.

PMID- 8542670
TI  - Demonstration of hereditarily accelerated proliferation in astrocytes derived
      from spontaneously hypertensive rats.
AB  - 1. We examined the proliferative rates of cultured astrocytes isolated from
      stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant
      spontaneously hypertensive rats (SHRSR). Wistar-Kyoto rats (WKY) were used as a
      control for SHRSP and SHRSR. 2. In the presence of 10% fetal bovine serum (FBS),
      the doubling time for astrocytes from SHRSP and SHRSR was significantly shorter
      than WKY. 3. When quiescent astrocytes derived from SHRSP or SHRSR were released
      from serum-deprivation, the DNA synthesis was stimulated 13.3-fold and 12.5-fold,
      respectively, whereas only a 7.76-fold increase was observed in WKY astrocytes.
      4. Further we studied the effects of two growth factors, epidermal growth factor
      (EGF) and fibroblast growth factor (FGF) on astrocytes proliferation. EGF induced
      greater DNA synthesis in SHRSP and SHRSR astrocytes compared with WKY astrocytes,
      although FGF had little or no effect. 5. Total cholesterol levels in SHRSP
      astrocytes and SHRSR astrocytes were significantly lower than that of WKY
      astrocytes, which was consistent with our previous observations in cultured
      vascular smooth muscle cells. 6. There was no difference in morphology among the
      cultured astrocytes from the three strains. 7. The abnormality of growth rate and
      cell membranes composition of astrocytes might be closely related to the genetic
      phenotypes (acute death of neurons and oedema of astrocytes) of SHRSP or SHRSR.

PMID- 8542671
TI  - Effects of captopril on [3H]-norepinephrine release in rat central nervous
      system.
AB  - 1. The present study was performed to investigate the effects of captopril (an
      angiotensin converting enzyme inhibitor, ACE-I) on noradrenergic transmission in
      the rat central nervous system. 2. Slices of rat hypothalamus and medulla
      oblongata were prepared and prelabelled with [3H]-norepinephrine. Slices were
      continuously superfused with Krebs-Ringer solution, and electrical stimulation (1
      Hz) was performed. 3. Captopril significantly inhibited the stimulation-evoked
      [3H]-norepinephrine release from rat hypothalamic slices in a dose-dependent
      manner (S2/S1 ratio: control 0.904 +/- 0.025, n = 6, captopril 1 x 10(-5) mol/L
      0.617 +/- 0.043, n = 6, P < 0.05, captopril 5 x 10(-5) mol/L 0.547 +/- 0.037, n =
      6, P < 0.05). However, the basal release of [3H]-norepinephrine was not affected
      by captopril. 4. Captopril also reduced the stimulation-evoked [3H]
      norepinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 +/-
      0.018, n = 6, captopril 3.3 x 10(-5) mol/L 0.624 +/- 0.046, n = 6, P < 0.05). 5.
      These results show that captopril might inhibit the stimulation-evoked
      norepinephrine release in rat hypothalamus and medulla oblongata. Although the
      precise mechanisms underlying the neurosuppressive effect of captopril are still
      uncertain, the finding suggests that the inhibition of noradrenergic transmission
      might be related to the central action of the ACE-I.

PMID- 8542672
TI  - Haemodynamic responses to rat adrenomedullin in anaesthetized spontaneously
      hypertensive rats.
AB  - 1. The haemodynamic effects of rat adrenomedullin (AM), a novel hypotensive
      peptide, were examined in anesthetized 16-18 week old spontaneously hypertensive
      rats (SHR) and Wistar-Kyoto rats (WKY). 2. An intravenous injection of rat AM
      dose-dependently reduced the mean blood pressure (MBP) with a concomitant fall in
      total peripheral resistance index (TPRI) and an increase in cardiac index (CI) in
      both strains of rats. Percent changes in MBP, TPRI and CI were not different
      between SHR and WKY. 3. The plasma half-life of rat AM in SHR was similar to that
      in WKY when it was administered at the dose of 1.0 nmol/kg. 4. These findings
      indicate that AM has a potent vasorelaxant activity in both SHR and WKY. The
      haemodynamic responsiveness to exogenous AM and its pharmacokinetics in SHR were
      comparable with those in WKY.

PMID- 8542673
TI  - Ciliary ultrastructure and beating activity in rat and guinea-pig respiratory
      mucosa.
AB  - 1. The rat and the guinea-pig are commonly used animals when the effects of drugs
      on ciliary activity in respiratory airways are studied. There are few data
      concerning the possible differences in ciliary function between these two
      animals. 2. Using a photodetector method we measured the ciliary beating
      frequency (CBF) from the upper part of the trachea, the lower part of the trachea
      and the distal part of the main bronchi (subsegmental bronchi) of rat and guinea
      pig respiratory tract. In addition, the structure of the cilia was studied using
      scanning electron microscopy (SEM). 3. CBF in the rat respiratory tract was
      significantly lower than in the guinea-pigs. In the upper trachea, the CBF for
      rat was 12.7 beats/s and 15.3 beats/s for guinea-pig. The respective values were
      9.2/16.0 beats/s in the lower part of the trachea and 6.9/13.8 beats/s in
      subsegmental bronchi. In both rats and guinea-pigs CBF was lower in the
      subsegmental bronchi than in the trachea (rat: 25.0-45.7%, guinea-pig: 9.8
      13.8%). 4. In addition to higher CBF, the quality of the photo-electrical signal
      was better from guinea-pig tissues, probably as a result of the larger amounts of
      ciliated cells and longer cilia of guinea-pig respiratory epithelial compared to
      those in rat mucosa. 5. SEM showed that the rat cilia were on average shorter
      (3.6 vs 4.3 microns) and thinner (0.19 vs 0.22 microns) than those of the guinea
      pig. Rat mucosa was markedly less ciliated than the respiratory mucosa of the
      guinea-pig.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542674
TI  - Whole body and renal noradrenaline release during acute infusion of endothelin-1
      in conscious sheep.
AB  - 1. The present study investigated in conscious sheep the response of the
      sympathetic nervous system to a systemic infusion of 20 nmol/h endothelin-1 (ET
      1), using a tritiated-noradrenaline (NA) tracer dilution technique. 2. Mean
      arterial pressure increased from 79 +/- 3 mmHg to a maximal level of 102 +/- 12
      mmHg by 30 min of ET-1 infusion. 3. Total and renal NA kinetics were measured
      during this time. Total NA spillover was not affected by infusion of ET-1. In
      contrast, renal NA spillover decreased from a control level of 81 +/- 5 to 30 +/-
      14 ng/min (P < 0.01) after 20 min and to 27 +/- 7 ng/min (P < 0.01) after 30 min
      of ET-1 infusion. 4. The present findings are consistent with the proposal that a
      direct vasoconstrictor action of ET-1 results in a paroreflex mediated reduction
      in renal sympathetic vasoconstrictor activity.

PMID- 8542675
TI  - Acute effect of ethanol on renal electrolyte transport in the rat.
AB  - 1. Despite human and animal studies, the direct effect of ethanol on renal water
      and electrolyte transport is poorly understood. The acute effect of increasing
      plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized
      rat model which inhibits endogenous arginine vasopressin (AVP) release. 2.
      Ethanol at a plasma concentration of 1.69 +/- 0.28 mmol/L produced an immediate
      increase in urine flow (174 +/- 11 microL/min pre-ethanol and 189 +/- 13 and then
      206 +/- 12 microL/min during the ethanol infusion; P < 0.01) as well as an
      increase in fractional sodium excretion (0.17 +/- 0.04 to 0.28 +/- 0.05 and 0.27
      +/- 0.05%; P < 0.01). There was also a brief phosphaturia. These increases in
      electrolyte excretion had returned to control values by 20 min despite a further
      increase in the plasma ethanol concentration. 3. The urinary excretion of
      potassium, calcium and magnesium was not altered nor was glomerular filtration
      rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did
      not alter the action of a maximal concentration of AVP (75 ng/kg) on water or
      electrolyte transport. However, the antidiuretic effect of a submaximal
      concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of
      1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis
      commonly ascribed to inhibition of AVP secretion may also be due to other
      intrarenal effects of ethanol, possibly acting within the proximal tubule. These
      results also confirm recent in vitro findings that while ethanol does not inhibit
      the action of a maximal concentration of AVP, it does modulate the effects of
      lower AVP concentrations.

PMID- 8542676
TI  - Prolactin induced analgesia is dependent on ATP sensitive potassium channels.
AB  - 1. The role of ATP sensitive potassium channels in the analgesic activity of
      prolactin (PRL) was studied in mice using glibenclamide and minoxidil, a blocker
      and an opener of these channel, respectively. 2. Pre-treatment with glibenclamide
      attenuated the analgesic activity of PRL while treatment with minoxidil
      potentiated the activity. 3. It is concluded that PRL, similar to morphine,
      utilizes ATP sensitive potassium channels in eliciting the analgesic response.

PMID- 8542677
TI  - The proportional cumulative area under the curve of paracetamol used as an index
      of gastric emptying in diabetic patients with symptoms of gastroparesis.
AB  - 1. The foreshortened 2 h method of measuring liquid gastric emptying (i.e. the
      proportional cumulative area under the curve of paracetamol) was utilized in
      diabetic patients in order to detect both gastroparesis and the influence of
      metoclopramide, a known prokinetic drug, on this condition. 2. Metoclopramide, 10
      mg intravenously, caused a significant increase in the median PCAUC from 20 min
      onwards. 3. In this study delayed gastric emptying was defined as a %PCAUC
      without pretreatment lower than the 5% percentile at 40, 60 and 90 min for normal
      volunteers. According to this criterion seven of the 10 patients with clinical
      symptoms of gastroparesis and/or peripheral neuropathy had delayed gastric
      emptying. 4. The PCAUC method would therefore seem to be a reliable model for
      investigating gastric emptying in diabetics and the effects of various prokinetic
      drugs on this condition.

PMID- 8542678
TI  - Comparison of responses to aminoguanidine and N omega-nitro-L-arginine methyl
      ester in the rat aorta.
AB  - 1. We have compared the effect of aminoguanidine with that of N omega-nitro-L
      arginine methyl ester on isolated thoracic aortic rings obtained either from
      endotoxin (lipopolysaccharide, 10 mg/kg, i.v. for 3 h) or vehicle (saline)
      treated rats. 2. Administration of endotoxin for 3 h resulted in a hypotension
      and a significant reduction of pressor responses to norepinephrine (1
      micrograms/kg, i.v.) in the anaesthetized rat. 3. In intact rings obtained from
      vehicle treated rats, aminoguanidine (0.3 and 1 mmol/L) had no significant effect
      on acetylcholine-induced relaxation (10(-9)-10(-5) mol/L), whereas N omega-nitro
      L-arginine methyl ester (0.3 mmol/L and 1 mmol/L) abolished that response,
      suggesting that aminoguanidine does not inhibit the activity of constitutive
      nitric oxide synthase. 4. Relaxation induced by L-arginine (10(-6)-10(-2) mol/L)
      was competitively inhibited by both aminoguanidine (0.3 mmol/L) and N omega-nitro
      L-arginine methyl ester (0.3 mmol/L) in endothelium-denuded aortic rings obtained
      from endotoxin treated rats. 5. Three hours of endotoxaemia was associated with
      an impairment of contraction to norepinephrine (10(-9)-10(-6) mol/L) in the
      endothelium-denuded aorta ex vivo. This hyporeactivity to norepinephrine was
      partially restored by treatment of the vessels either with aminoguanidine (0.3
      mmol/L) or with N omega-nitro-L-arginine methyl ester (0.3 mmol/L) in vitro. 6.
      These results in isolated thoracic aortae of the rat reinforce that
      aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase,
      whereas N omega-nitro-L-arginine methyl ester is a non-selective inhibitor of
      both the inducible and constitutive nitric oxide synthase.

PMID- 8542679
TI  - Functional and structural characteristics of experimental FK 506 nephrotoxicity.
AB  - 1. FK 506 (Tacrolimus, Prograf) is a novel immunosuppressant which is effective
      in solid organ transplantation and autoimmune diseases. The lack of a suitable
      animal model has hindered the study of the nephrotoxicity of the drug which has
      emerged as a common adverse effect in clinical trials. We report both acute and
      chronic nephrotoxicity with tacrolimus (FK) in which renal structure and function
      are worsened by sodium depletion. 2. Pair fed male Sprague-Dawley rats were given
      FK (3 or 6 mg/kg, p.o.) or vehicle for 7, 21 and 42 days on low salt or normal
      diet. The FK whole blood trough levels achieved (3-10 ng/mL) were similar to
      those observed in FK treated transplant patients. 3. In salt depleted animals
      treated for 7 days, FK (6 mg/kg) decreased renal blood flow and glomerular
      filtration rate (1.8 +/- 0.1 and 0.2 +/- 0.1 mL/min per 100 g vs 2.9 +/- 0.2 and
      1.1 +/- 0.1 mL/min per 100 g in the vehicle group, P < 0.01). 4. After 21 days of
      treatment of FK on low salt diet but not normal salt, FK induced focal collapse
      and vacuolization in proximal tubules and discrete or confluent zones of
      tubulointerstitial oedema and mononuclear cell infiltration. 5. After 42 days in
      salt depleted rats, there was significant tubulointerstitial scarring that was
      associated with an increased plasma renin activity (PRA) (64 +/- 10 vs 30 +/- 4
      ng AI/mL per h in the vehicle group, P < 0.05). Animals given normal salt diets
      did not develop significant histological lesions even up to 42 days.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8542680
TI  - Increased blood pressure and changes in membrane lipids associated with chronic
      ethanol treatment of rats.
AB  - 1. Changes in membrane fluidity have been proposed to contribute to the
      pathogenesis of ethanol-induced hypertension possibly through changes in membrane
      lipid patterns, but reports are inconsistent. 2. In a controlled trial we
      documented ethanol-induced changes in blood pressure and composition of membrane
      lipids in ethanol-fed rats. 3. Systolic blood pressure increased significantly in
      the ethanol-treated rats (9.3 mmHg, s.e.m. 2.9) compared with the control group (
      1.3 mmHg, s.e.m. 2.6). Mean cholesterol content in red cell membranes did not
      differ significantly between ethanol-fed and control rats. Phospholipids of
      aorta, red cells and kidney showed a significant decrease in the polyunsaturated
      to saturated fatty acid ratio, while membrane phospholipids from the heart showed
      a significant increase in the polyunsaturated to saturated fatty acid ratio with
      ethanol treatment. 4. In univariate regression blood pressure was significantly
      negatively related to levels of arachidonic acid in the kidney (P = 0.0013) and
      to linoleic acid in the aorta (P = 0.0341) and red cells (P = 0.0289). Blood
      pressure was not significantly related to fatty acids in the heart nor to
      membrane cholesterol or phospholipids. 5. Differences in fatty acid composition
      of phospholipids between controls and ethanol-fed rats are consistent with
      altered membrane fluidity. Altered membrane function is a potential mechanism
      involved in ethanol-induced hypertension.

PMID- 8542681
TI  - Effects of a continuous infusion of dopamine on the ventilatory and carotid body
      responses to hypoxia in cats.
AB  - 1. We investigated how a continuous infusion of dopamine (DA; 5 micrograms/kg per
      min), which is often used clinically, would affect the ventilation and carotid
      chemoreceptor neural activity in anaesthetized cats. 2. In anaesthetized,
      spontaneously breathing cats, tidal volume (VT) and respiratory frequency (f)
      were continuously monitored at five levels of inspired oxygen (PIO2 = 110, 130,
      150, 170, 760 mmHg) during Da or saline infusion. VT and f were sampled for 1 min
      after 3 min exposure to each level of PIO2. Time control study was also
      performed. 3. DA infusion significantly lowered VT under both normoxia and
      hypoxia in seven of eight cats. Respiratory frequency was not affected by DA
      infusion. Depression of ventilation during post-hypoxic hyperoxia was augmented
      by DA infusion. Chemodenervation abolished the ventilatory response to hypoxia
      and DA did not further affect the ventilatory response to hypoxia. 4. In a second
      group of artificially ventilated cats, carotid chemoreceptor neural activity was
      recorded at five levels of arterial oxygen tension. DA infusion significantly
      depressed carotid chemoreceptor neural activity during normoxia and hypoxia in
      six of seven cats. 5. These findings suggest that changes in ventilation during
      low dosage of DA infusion closely correlate with carotid body neural output. A
      predominant effect of this dosage of DA (5 micrograms/kg per min) was depression
      in the ventilatory response to hypoxia due to an inhibition of carotid body
      neural output.

PMID- 8542682
TI  - Effect of an antihypertensive drug on brain angiotensin II levels in renal and
      spontaneously hypertensive rats.
AB  - 1. Although numerous studies suggest that brain angiotensin (AII) may play an
      important role in the regulation of blood pressure, it is still unclear what
      factors may influence brain AII. In this study, we hypothesized that brain AII is
      influenced by circulating factors. To investigate the role of blood pressure and
      plasma AII in brain AII level, we studied the effect of an antihypertensive drug
      on brain AII in two-kidney, one-clip (2K1C) and spontaneously hypertensive (SHR)
      rats. 2. Hydralazine (20 mg/kg per day) and vehicle (water) were given to 2K1C
      rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition,
      vehicle was applied to sham operated rats and Wistar-Kyoto (WKY) rats. Brain and
      plasma AII was measured by a highly sensitive radioimmunoassay coupled with high
      performance liquid chromatography. 3. Hydralazine treatment effectively lowered
      blood pressure to the same level of sham-operated and WKY rats. 2K1C rats showed
      significantly higher plasma AII than sham rats, but hydralazine treatment did not
      show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats
      showed a significantly higher level than sham rats. Interestingly, hydralazine
      treatment diminished this increase in brain AII. In contrast, SHR showed higher
      brain AII levels in the hypothalamus, brainstem and cerebellum than in WKY rats,
      whereas there was no significant change in plasma AII concentration between SHR
      and WKY rats. In contrast to the results found in 2K1C rat experiments,
      hydralazine treatment failed to decrease brain AII levels despite lowered blood
      pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542683
TI  - Comparison of the attenuating effects of four beta-adrenoceptor agonists on rat
      isolated uterus and aorta.
AB  - 1. The ability of four beta-adrenoceptor agonists to attenuate oxytocin (0.2, 2
      and 20 nmol/L) or KCl (20, 40 and 80 mmol/L)-induced contractions of the uterus
      (n = 5-8 for each agonist) and the KCl (18 mmol/L)-induced contractions of the
      aorta (n = 9 for each agonist) from rats, pretreated with oestradiol has been
      compared. 2. Isoprenaline, salbutamol, terbutaline and procaterol (0.1-10
      mumol/L) attenuated the contractions of the uterus and the aorta. All four
      agonists had similar attenuating potencies on the uterus. 3. Procaterol caused
      the same maximal attenuation (33%) on the aorta as the other beta-adrenoceptor
      agonists and is thus acting as a full beta 2-adrenoceptor agonist under these
      experimental conditions. Isoprenaline and procaterol were much more potent than
      salbutamol and terbutaline in attenuating the aorta responses. 4. This study
      showed that isoprenaline and procaterol were potent attenuants on both the uterus
      and aorta whereas salbutamol and terbutaline were potent uterine but only modest
      aorta attenuants. This preliminary study indicates that the responsiveness of
      uterine and vascular tissue to certain beta 2-adrenoceptors differs.

PMID- 8542684
TI  - Regional difference of endogenous ATP release in the pulmonary artery of rabbits.
AB  - 1. The release of adenyl purines such as ATP, ADP, AMP and adenosine, from the
      pulmonary artery trunk (PAT), extrapulmonary artery (EPA) and intrapulmonary
      artery (IPA) were compared. 2. The amount of basal overflow of adenyl purines
      from the PAT was significantly smaller than those from EPA and IPA. There was no
      significant difference between the amount of the overflow from EPA and PAT. 3.
      Methoxamine, an alpha 1-adrenoceptor agonist, significantly increased the
      overflow of adenine nucleotides from the PAT, EPA and IPA, but did not increase
      those of adenosine. Methoxamine-induced release of adenyl purines from IPA was
      significantly larger than those from EPA and PAT. 4. These results suggest that
      an alpha 1-adrenoceptor-mediated mechanism for ATP-release is not homogeneously
      distributed in the pulmonary artery and a larger amount of ATP may be released in
      the peripheral part of the artery.

PMID- 8542685
TI  - Variations in the anatomy of the scapula with reference to the snapping scapula.
AB  - Two clinical cases led to an examination of 700 scapular dry bone specimens in an
      effort to understand variations in anatomy of possible relevance to the
      development of a painful snapping scapula. The medial superior border and the
      inferior pole of the scapula respectively displayed areas of bony variability
      that appeared to be of clinical consequence in these 2 cases. The 2 areas are
      common sites of clinical symptomatology in the painful snapping scapula.
      Variations in the bony anatomy require consideration during the workup and
      evaluation of this condition.

PMID- 8542686
TI  - Repair of the distal biceps tendon using suture anchors and an anterior approach.
AB  - The authors describe a technique for repair of the biceps tendon rupture from the
      radial tuberosity. A single anterior incision, limited volar dissection, and
      implantable bone anchors were used. With this technique, the authors have
      repaired the distal biceps tendon in 5 men (mean age, 39 years). Four patients
      were laborers and 1 was an athlete. Mechanism of injury was a single traumatic
      event with an unanticipated large load being applied to the flexed arm. Four
      patients were treated acutely and 1 was treated 6 months after injury. All
      patients returned to preinjury activity levels by 5 months after repair of the
      tendon. Clinically, all repairs remained intact (mean followup, 2.5 years). Range
      of motion was symmetric. No evidence of associated nerve injuries, heterotopic
      bone formation, or olecranon tenderness occurred. Subjective, as well as
      objective, results were excellent in those 5 patients whose distal biceps tendon
      was repaired by the single volar incision and implantable anchors.

PMID- 8542688
TI  - External spinal skeletal fixation in the management of back pain.
AB  - External spinal skeletal fixation, pioneered by the Association for the Study of
      Internal Fixation as an alternative in thoracolumbar fracture management, has
      been effective in temporarily relieving mechanical low back pain. This
      investigational technique was been proposed as an alternative in the selection of
      patients with back pain as candidates for pain relief through fusion. This is the
      report of a prospective and randomized clinical trial that has defined prognostic
      benefit (good outcome in 61% of control patients versus 90% of the study group)
      in selecting patients with mechanical back pain (verified through facet blocks or
      discograms) as candidates for pain relief through fusion surgery.

PMID- 8542687
TI  - Phasic relationships of the intrinsic and extrinsic thumb musculature.
AB  - Dynamic electromyography has proven to be useful in testing patients with spastic
      disorders who are candidates for tendon transfer or lengthening operations. The
      purpose of this investigation was to define the normal phasic activity of the
      thumb muscles during simple, reproducible activities. Fine wire electrode pairs
      were inserted into the extensors pollicis longus and brevis, abductors pollicis
      longus and brevis, flexors pollicis longus and brevis, opponens pollicis,
      adductor pollicis, and first dorsal interosseus of 5 normal subjects. Motions of
      the carpometacarpal joint and the interphalangeal joint of the thumb were
      recorded by electrogoniometer. Proximal joint positions were controlled by the
      subject at the elbow, forearm, and wrist. Normal timing was described for each
      muscle during hand opening and closing, key pinch with and without force, and
      opposition pinch with and without force. The data support the concept of
      individual motor strategies: normal persons often select different combinations
      of muscles to accomplish a functional goal.

PMID- 8542689
TI  - Etiologies of shoulder pain in cervical spinal cord injury.
AB  - A protocol including physical examination, plain radiography, and shoulder
      arthrography was designed to study prospectively the causes of shoulder pain in
      patients with cervical spinal cord injury. Twenty-four patients (30 shoulders)
      were studied and subdivided into acute and chronic groups. The causes of shoulder
      pain in the acute group of 11 patients (15 shoulders) included capsular
      contracture or capsulitis or both in 6 shoulders; rotator cuff tears in 4;
      anterior instability in 2; and rotator cuff impingement, osteoarthritis with
      osteonecrosis, and osteoarthritis in 1 each. Of 13 patients (15 shoulders)
      assigned to the chronic group, the diagnoses included anterior instability in 5
      shoulders; multidirectional instability in 3; capsular contracture or capsulitis
      or both in 3; and Charcot arthropathy, rotator cuff tear, rotator cuff
      impingement, and scapular pain in 1 each. To prevent and treat shoulder pain,
      therapeutic protocols for these patients must be individualized after a correct
      diagnosis is made.

PMID- 8542690
TI  - Vulnerability of vertebral artery in anterolateral decompression for cervical
      spondylosis.
AB  - This study aimed to provide anatomic data for the location of the vertebral
      artery and offer an optimal approach for lateral cervical decompression that
      minimizes the risk of injury to the vertebral artery. Anatomically, there has
      been little study documenting the safe zone to prevent vertebral artery injury
      during the resection of the uncinate process or uncovertebral joint during the
      lateral decompression of the nerve root. The transverse foramen and its related
      parameters were measured on dry cervical spines from C3 to C7. The cadaveric
      cervical spines were dissected to determine a method for resection of the
      uncovertebral joint with decreased risk of vertebral artery laceration. The
      anteroposterior diameters of the transverse foramina gradually decreased from C6
      to C3. The transverse diameters of the transverse foramina were smaller at C5.
      The interforaminal distance, width of the vertebrae, interuncinate distance, and
      the distance from the lateral tip of the uncinate process to the medial border of
      the transverse foramen became smaller in more cephalad vertebrae. After subtotal
      vertebrectomy and opening of the anterior walls of the transverse foramina, the
      resection of the uncovertebral joint and lateral decompression became easier and
      safer. Anatomic measurements obtained in this study indicate the vertebral artery
      to be at risk during decompression of the more cephalad vertebrae. The lateral
      decompression can be completed under direct vision with smaller rongeurs and
      curettes, rather than with high speed burr after deroofing the anterior walls of
      transverse foramina and retracting the vertebral artery laterally.

PMID- 8542691
TI  - Multiple loose bodies: formation, revascularization, and resorption. A 29-year
      followup study.
AB  - A 45-year-old patient sustained a traumatic dislocation of 1 hip. During a 29
      year period, 10 to 13 multiple calcified loose bodies developed slowly in the
      hip. These first grew in size and became very radiodense, but later showed
      progressively less radiodensity. Progressive osteoarthritis of the hip was the
      indication for hip arthrotomy. The loose bodies had become reattached to the
      synovial surface of the hip joint and were revascularized, having converted from
      calcified cartilage to bone. This case dramatically shows the body's mechanism
      for attempting to remove loose bodies from joints.

PMID- 8542692
TI  - Mast cells in loosening of totally replaced hips.
AB  - This study evaluated mast cells in tissue around loose total hip implants.
      Interface and pseudocapsular tissues were obtained from 6 patients with a loose
      hip prosthesis. Mast cells were labeled with monoclonal mouse antihuman
      antibodies against tryptase and chymase in avidin-biotin-peroxidase complex
      staining and were quantitated morphometrically by means of a semiautomatic
      Kontron image analyzer. Almost all mast cells in situ were chymase-positive and
      tryptase-positive connective tissue cells. The mean number of such cells per mm2
      of tissue increased in this rank order: interface (9.98 +/- 5.03 cells) <
      pseudocapsule (15.85 +/- 4.99 cells) < control knee synovium (25.08 +/- 8.64
      cells). Mast cells in periprosthetic tissue, in contrast to normal knee synovial
      tissue, exhibited granule release. Mast cells around loose hip prostheses
      appeared to be activated by connective tissue mast cells. These were found in
      diminished numbers and in a degranulated state in the interface tissue between
      implant and bone. Mast cell activation in loco may thus lead to significant local
      production and/or release of proinflammatory mast cell mediators. Prevention of
      mast cell activation (degranulation) could prove useful in the postponement of
      loosening of the totally replaced hip.

PMID- 8542693
TI  - Biodegradable pin fixation of osteochondral fragments of the knee.
AB  - The authors present 3 cases of osteochondritis and 2 cases of osteochondral
      fracture of the knee. These cases were treated with a bioabsorbable ultra high
      strength poly (L-lactide) pin, which has the highest mechanical strength value of
      any nonfiber reinforced poly (L-lactide) reported previously. Three of the
      patients were male, and 2 were females; their ages ranged from 12 to 21 years.
      The followup period ranged from 2 years to 7 years 9 months (mean, 4.1 years).
      Two to 4 poly (L-lactide) pins with a diameter of 2 mm were used to fix the
      osteochondral fragments or the transplanted autogenous osteochondral grafts. In
      all cases, satisfactory bone union was obtained, and no inflammatory reaction was
      observed during the entire followup periods. The ranges of motion were normal,
      and there was no pain in any of the cases. It is concluded that the poly (L
      lactide) pin is safe and useful in the repair of osteochondral fractures of the
      knee and in fixing grafted osteochondral fragments.

PMID- 8542694
TI  - Late reconstruction of patellar ligament ruptures using Ilizarov external
      fixation.
AB  - Chronic patellar ligament ruptures, on which failed reconstruction attempts have
      been made, cause structural changes in the quadriceps mechanisms with marked
      fixed proximal migration of the patella. Before reconstruction, the position of
      the patella must be normalized. When using Ilizarov principles and an Ilizarov
      external fixator to treat these ruptures, full weightbearing and range of motion
      can be maintained throughout the pre- and postreconstruction period. This
      previously unreported technique has been used in 2 patients with chronic patellar
      ligament ruptures in whom reconstruction attempts had failed. Successful results
      obtained with this procedure warrant its consideration for this rare but
      disabling problem.

PMID- 8542695
TI  - Extendible endoprostheses for the skeletally immature.
AB  - Aseptic loosening was identified as the predominant cause of implant related
      failure in a retrospective study of a consecutive series of 168 Stanmore custom
      made extendible endoprosthetic replacements used in skeletally immature patients.
      Most of the replacements were used in the treatment of bone tumor and the
      remainder for the revision of failed massive endoprosthetic replacements. Since
      the first Stanmore extendible endoprosthesis was inserted in 1976, 4 types of
      extension mechanisms have been used. Thirty eight of the 164 cases with followup
      data were revised, of which 19 were as a result of aseptic loosening. Survival
      analysis revealed that the overall probability of surviving an implant related
      failure was 0.512 (+/- 0.005) at 5 years, highlighting the high complication rate
      of these extendible replacements that required a revision procedure. Sixteen of
      the 19 aseptic loosening cases were distal femoral replacements. The probability
      of a patient with a distal femoral replacement surviving aseptic loosening was
      0.773 (+/- 0.008) at 5 years. Other modes of implant related failure included
      jamming of the extending mechanism, infection, and maximum extension of the
      replacement before skeletal maturity had been reached.

PMID- 8542696
TI  - Multifocal pigmented villonodular synovitis in a child. A case report.
AB  - Pigmented villonodular synovitis is a well-described disease that almost
      universally involves a single site. This is a report of an unusual case of
      multiple site involvement of pigmented villonodular synovitis in a child. In
      addition to multiple site involvement, the case is unusual for several reasons:
      asymmetric involvement, involvement of both upper and lower extremities,
      involvement of the pes anserine tendons, and the patient is an otherwise healthy
      child.

PMID- 8542697
TI  - Low grade central osteogenic sarcoma. A long-term followup of 20 patients.
AB  - Osteogenic sarcoma is a heterogeneous family of tumors that has a variable
      biologic behavior. Low grade central osteogenic sarcoma is an uncommon form that
      is characterized by a long premorbid history and is compatible with prolonged
      survival after treatment. Twenty cases of low grade central osteosarcoma with
      long-term followup (16 [2.5-48] years) were studied retrospectively. The age
      distribution was broad (range, 15-83 years). All tumors arose in the lower limb.
      The primary symptom was pain; mean duration was 44 months (range, 1-180 months).
      A diagnosis of low grade central osteosarcoma was made primarily for 11 patients.
      For 9 others, fibrous dysplasia (3), nonossifying fibroma (2), fibroma (1),
      chondromyxoid fibroma (1), chondrosarcoma (1), and simple bone cyst (1) were
      diagnosed initially. Intralesional surgery was associated with recurrence in
      every case. Radical margins were not associated with local recurrence. Four
      recurrences were higher grade and 1 was dedifferentiated. Three of 4 patients
      with metastases died of their disease. Five- and 10-year survival was 90% and
      85%, respectively. Histology and radiology are complementary for confirming the
      diagnosis. Low grade central osteosarcoma seems to be controllable by surgery
      alone if at least wide margins are used.

PMID- 8542698
TI  - Allograft-prosthesis composite versus megaprosthesis in proximal femoral
      reconstruction.
AB  - A review of 33 patients who underwent proximal femoral resection for primary bone
      tumor and reconstruction with an allograft-prosthesis composite or a
      megaprosthesis is presented to consider the relative merits of the 2 procedures.
      Clinical function, reconstruction survival, and associated complications were
      analyzed. Eighteen composites in 16 patients and 18 megaprosthesis in 17 patients
      were analyzed. Infection in the composite group and instability in the
      megaprosthesis group were the common causes of failure and removal of
      reconstructions. The average functional evaluation in 14 surviving patients with
      composites was 87% of normal. In 10 surviving patients with megaprostheses, the
      average function was 80% when complications were avoided. Survival analysis of
      the patients with reconstructions showed a 10 year survival of 76% for the
      patients with composites and 58% for those with megaprostheses. Both composite
      and megaprosthetic reconstruction of the proximal femur seem to function equally
      well from the perspective of function and survival because no statistically
      significant difference could be shown by this review.

PMID- 8542699
TI  - The expression of mRNA for insulin-like growth factors and their receptor in
      giant cell tumors of human bone.
AB  - Insulin-like growth factors I and II are among the most abundant growth factors
      found in bone, and their expression also has been reported in a variety of
      neoplastic tissues. Using the technique of in situ hybridization, the authors
      have studied the expression of the messenger ribonucleic acid (mRNA) for insulin
      like growth factors I and II and the Type I insulin-like growth factor receptor
      in giant cell tumors of human bone (n = 8). The expression of the mRNA for
      insulin-like growth factors I and II and the Type 1 insulin-like growth factor
      receptor was observed in giant cells and in the mononuclear stromal cell
      component but not in cells of the fibrous connective tissue at the growing edge
      of the tumor. The multinucleated cells expressed tartrate resistant acid
      phosphatase and showed reactivity with osteoclast selective monoclonal
      antibodies, confirming the close relationship between these giant cells and
      osteoclasts. Thus, these results are consistent with the possibility that locally
      produced insulin-like growth factors have an important regulatory role in the
      growth and development of giant cell tumors of bone. In addition, they suggest
      that these growth factors may function as autocrine or paracrine regulators of
      the proliferation of differentiation of cells of the osteoclast lineage.

PMID- 8542700
TI  - Ewing's sarcoma of the proximal femur.
AB  - The cases of 16 patients with Ewing's sarcoma of the proximal femur treated in
      the era of multiagent chemotherapy were reviewed, with emphasis on the mechanical
      problem of tumor involvement in this structurally demanding site. Fourteen
      patients received chemotherapy and local radiotherapy as the initial primary
      treatment. One patient had chemotherapy and radiotherapy, followed by wide local
      resection. One patient had amputation, followed by chemotherapy, for pathologic
      fracture and extensive soft tissue involvement at presentation. Two local
      recurrences occurred. Excluding the 2 patients whose femurs were fixed
      prophylactically, the pathologic fracture rate was 79%. In addition, by excluding
      the 2 patients who died before fracture, the pathologic fracture rate was 92%.
      Nonunion occurred in 5 (71%) of the 7 pathologic fractures not treated by
      resection and required as many as 5 additional surgical procedures to obtain
      union. At latest followup evaluation (average, 6.3 years), 10 patients had no
      evidence of disease, 1 was alive with disease, and 5 had died of their disease.
      Options for management should include primary resection and reconstruction or
      prophylactic internal fixation after completion of chemotherapy plus or minus
      radiotherapy.

PMID- 8542701
TI  - Multicentric giant cell tumor of bone.
AB  - Giant cell tumor of bone accounts for 4% to 5% of primary bone tumors in the
      United States. Multicentric giant cell tumors occur in < 1% of all patients with
      giant cell tumors, and only 43 patients with multicentric giant cell tumor have
      been reported on in the literature. This series presents 3 additional cases of
      multicentric giant cell tumor, includes updated data for 2 patients previously
      reported on in the literature, and reviews 24 cases previously reported on in
      detail in the literature. The mechanism by which giant cell tumor involves
      multiple locations is not known. Multicentric giant cell tumor, in contrast to
      unifocal giant cell tumor, has a tendency to involve the hands, feet, and
      metaphysis/diaphysis of long bones and to occur in a slightly younger population.
      In 15 of the 29 patients reviewed, a second lesion did not develop for > 2 years
      after their initial presentation. Eighteen of those 29 patients had > 2 sites of
      tumor involvement, 1 of whom had 11 lesions. Two of the 5 patients in the
      authors' series presented with a spectrum of disease activity, with latent,
      active, and aggressive lesions present throughout the observation period.

PMID- 8542702
TI  - Influence of callus deformation time. Bone chamber study in rabbits.
AB  - Short periods of strain have effects on tissue differentiation in a skeletal
      defect. Little is known about the importance of the duration of such periods. The
      authors compared 2 short daily periods of strain pulses that differed only by
      their duration. This was done by using the micromotion chamber, which is a
      titanium implant with a transverse intraosseous canal. Fibrous tissue forms in
      the canal and then is replaced by bone through membranous (metaplastic)
      ossification. The tissue in the canal can be exposed to cyclic deformation. The
      chamber allows harvest of the tissue within the canal without disturbing the
      outer parts of the implant or the surrounding bone, thus enabling repeated
      experiments in the same animal. Chambers were inserted in 6 rabbits and
      repeatedly harvested at 3-week intervals. Between harvests, the chambers were
      subjected to either no motion, 20 cycles once daily during 20 seconds (1 Hz), or
      20 cycles once daily during 120 seconds (0.17 Hz). Altogether 39 harvested
      specimens were studied. The 20-second treatment tended to increase the amount of
      ingrown bone as compared with no motion, whereas the 120-second treatment caused
      a marked decrease in bone formation and increase in fibrous tissue. Because the
      acute tissue trauma appears similar with both deformation treatments, it would
      appear that the increased fibrous tissue formation with the longer deformation
      time is caused by the parameters of tissue deformation and not by increased
      tissue damage.

PMID- 8542703
TI  - Pressure generation beneath a new thermoplastic cast.
AB  - A new cast immobilizer that is heat-shrunk to conform to an injured extremity was
      examined. The purpose of these studies was to compare pressures beneath the
      thermoplastic cast with those beneath fiberglass casts on a laboratory model and
      on the forearms of human volunteers. Pressures measured beneath fiberglass casts
      on metal cylinders averaged 36 mm Hg. Thermoplastic casts on the smaller cylinder
      that allowed 42% shrinkage produced a mean pressure of 25 mm Hg; those placed on
      the larger cylinder that allowed 17% shrinkage produced a mean pressure of 39 mm
      Hg. Pressures measured on the forearms of healthy volunteers averaged 22 mm Hg
      beneath fiberglass casts and 31 mm Hg beneath the thermoplastic casts. These
      pressures were considerably less than pressures that have been shown to occlude
      the microcirculation of the skin. Acute compartment syndromes result from
      swelling within a limited space and remain a serious concern clinically when
      swelling is anticipated under any type of constraining cast. The results of these
      studies indicate that the new cast should not produce a greater risk of
      circulatory compromise to the limb than previously used fiberglass materials.

PMID- 8542704
TI  - Human macrophage response to retrieved titanium alloy particles in vitro.
AB  - Titanium alloy particles were isolated from membranes obtained at revision
      arthroplasty. Addition of these retrieved particles to human
      monocytes/macrophages in cell culture resulted in morphologic change and
      metabolic activation. Cells exposed to these particles actively phagocytized the
      metallic debris, resulting in an increase in cytoplasm and a polarization of
      ingested metal. The metabolic response of the macrophages included increased
      release of prostaglandin E2, interleukin-1 beta, interleukin-6, and tumor
      necrosis factor-alpha, and increased hexosaminidase activity. Increased release
      of interleukin-1 beta was maximal 6 to 12 hours after particle exposure. These
      data show that retrieved titanium alloy particles activate macrophages in vitro
      in an analogous fashion to that observed around failed arthroplasties.

PMID- 8542705
TI  - The effects of patellar thickness on patellofemoral forces after resurfacing.
AB  - The purpose of this study was to determine the effect of patellar bone and
      patellar implant thickness on patellofemoral forces after resurfacing in total
      knee arthroplasty. Seven cadaver knees were tested using an Oxford Knee Testing
      Rig. This model gave the specimens 6 degrees freedom while dynamic data were
      collected. Each knee was tested from full extension to 95 degrees knee flexion.
      Knees were implanted with Press Fit Condylar femoral, tibial, and patellar
      implants. The effect of varying patellar thickness on patellofemoral forces was
      determined by using custom modular oval-domed polyethylene patellar components
      with progressive thickness increments of 2 mm. Patellofemoral forces were
      measured by a custom-designed uniaxial patellar load cell. Statistically
      significant increases in patellofemoral compression forces were found from 70
      degrees to 95 degrees flexion with increased patellar bone and patellar implant
      thickness.

PMID- 8542706
TI  - A worldwide study on the seasonal variation of slipped capital femoral epiphysis.
AB  - The records of 1630 children (671 girls, 959 boys) with 1993 slipped capital
      femoral epiphyses were reviewed. These children were from all 6 continents and 33
      orthopaedic centers. The month of the slip onset was defined as the month when
      the patient presented to the physician minus the duration of symptoms as reported
      by the patient. There was a significant variation in the month of onset for the
      children from North America and Europe, but not Africa, Asia, Australia/New
      Zealand, or South America. The peak month of onset was 6.8 +/- 2.6 in North
      America (late June) and 7.9 +/- 2.4 in Europe (late July). This phenomenon of
      slips occurring significantly more often in the summer months was only present
      when the children lived north of the 40 degrees N latitude.

PMID- 8542707
TI  - The influence of clinical factors on periprosthetic bone remodeling.
AB  - The femurs of 11 patients with well-functioning unilateral hip replacements were
      retrieved at autopsy and analyzed for periprosthetic bone remodeling by dual
      energy xray absorptiometry. Each case involved a femur with a porouscoated
      endoprosthesis; the endoprosthesis remained implanted for an average of 5.9
      years. In the contralateral femur, a matching prosthesis was implanted in vitro,
      to serve as a control for comparisons. There was an average 22.6% decrease in
      bone mineral content in the in vivo implanted femur (range, 5.4%-47.4%). Females
      experienced an average bone loss of 31.2%, which was significantly higher than
      the 12.3% average loss in males. Longitudinal analysis revealed an average
      decrease in bone mineral content of 42.1% proximally, 23% in the midsection, and
      5.5% distally. Percent decreases in total bone mineral content were correlated
      with the following clinical variables: weight, age, implant diameter, duration of
      implantation, and contralateral femoral bone mineral content. Only the bone
      mineral content of the contralateral femur had a strong predictive value. Bone
      loss was greater in femurs with low bone mineral content than in those with high
      bone mineral content. Weight, age, implant diameter, and duration of implantation
      were not correlated with bone loss.

PMID- 8542708
TI  - Knee pain in a 30-year-old man.

PMID- 8542709
TI  - Magnetic resonance imaging of the musculoskeletal system. II. The hip.
AB  - Magnetic resonance (MR) imaging of the hip joint and adjacent structures can
      provide valuable information under many clinical circumstances. After plain
      radiography, MR imaging is arguably the modality of choice for the detection of
      osteonecrosis, occult fractures, primary and secondary neoplasms, and in the
      assessment of some soft tissue abnormalities. The accuracy of MR imaging is
      dependent on technical factors, such as magnet field strength, surface coils, and
      sequence selection. Low resolution MR images generally are satisfactory for
      screening for osteonecrosis and for the evaluation of large bone or soft tissue
      abnormalities. Tailoring an examination with high resolution images, specialized
      sequences, or contrast may add useful information, particularly if a detailed
      evaluation of the joint is desired. Tailoring of the examination by an
      experienced radiologist requires adequate clinical information, so communication
      between the referring physician and radiologist is crucial for optimal results.
      Finally, MR imaging and radiographs are complementary examinations; MR images of
      the hip should not be interpreted without having recent radiographs available for
      comparison.

PMID- 8542710
TI  - On necrosis of the joint cartilage by epiphyseolysis capitis femoris. 1930.

PMID- 8542711
TI  - The torsional basis for slipped capital femoral epiphysis.
AB  - Fifteen moderate to severe acute slipped capital femoral epiphyses were
      manipulated in 15 patients to correct significant deformities; in each case,
      torsion played a critical role in the reduction. Nine of 15 patients with acute
      slips underwent controlled, open reduction from the anterolateral approach,
      stabilizing the epiphysis while the metaphysis was internally rotated, flexed,
      and abducted; none had osteonecrosis or chondrolysis. The other 6 acute slips
      were treated with traction using internal rotation to achieve closed reduction; 2
      of these 6 closed reductions progressed to osteonecrosis, and both were reduced
      in an uncontrolled situation. Of the 15 acute slips, 6 involved torsion as the
      primary force. Based on the importance of torsion in all the reductions and the
      prevalence of torsion as an etiologic factor in the initial slips, it is
      postulated that torsion is an important contributing component in the etiology of
      slipped capital femoral epiphysis. Despite 2 cases of osteonecrosis in unstable
      hips, these 15 manipulative reductions were 87% successful. If the 2 inadvertent
      closed reductions are eliminated, then the success rate is 100%.

PMID- 8542712
TI  - Natural history of untreated chronic slipped capital femoral epiphysis.
AB  - From 1915 to 1952, 31 hips in 28 patients with slipped capital femoral epiphysis
      were observed without interventional treatment at the University of Iowa
      Department of Orthopaedic Surgery. A slip was considered chronic if the symptoms
      had been present for 3 weeks or more. The severity of the slip was determined by
      radiographs. Assessment included Iowa Hip Rating and grading of radiographic
      degenerative changes. The mean duration of patient followup from the onset of
      symptoms was 41 years. The mean patient age was 54 years old at review, and 13
      years old at onset of symptoms. Degenerative arthritis developed in hips with
      displaced slipped capital femoral epiphysis. Untreated slipped capital femoral
      epiphysis can progress to a severe degree. The natural history of chronic slipped
      capital femoral epiphysis is favorable provided that displacement is minimal and
      remains so.

PMID- 8542713
TI  - Cuneiform osteotomy of the femoral neck in severe slipped capital femoral
      epiphysis.
AB  - From 1978 through 1988, 27 severe slipped epiphyses (Grade III) in 23 adolescent
      patients were treated with a cuneiform osteotomy of the proximal neck of the
      femur. Average time of followup was 8 years 5 months. The results were graded by
      the criteria of Southwick, with emphasis on pain, function, range of motion, and
      radiographic appearance. Arbitrarily, no hips were rated excellent, because the
      authors thought that this rating should be reserved for normal hips that have not
      had any disease process nor surgical procedure. There were 19 good, 4 fair, and 4
      poor results. The 4 poor results were in patients with avascular necrosis. The
      avascular necrosis rate was 15%. Eight hips had some joint space narrowing during
      the postoperative followup period. All joint space narrowing was resolved by 20
      months postoperatively. All patients, including those with avascular necrosis,
      improved in joint flexion and joint internal rotation. Although the avascular
      necrosis rate of 15% is significant, the authors believe that the potential for
      restoring hip anatomy and providing a normally functioning hip in the adolescent
      patient makes this procedure a viable treatment option.

PMID- 8542714
TI  - Allograft epiphysiodesis for slipped capital femoral epiphysis.
AB  - During this retrospective investigation, use of freeze-dried irradiated allograft
      for achieving epiphysiodesis in patients with Grade I or Grade II slipped capital
      femoral epiphyses was evaluated. The study reviewed 40 grafting procedures in 33
      patients: 20 patients were boys and 13 were girls, whose average age was 13 years
      old. The group included 31 Grade I slips and 9 Grade II slips. Six were unstable
      and 34 were stable. Procedure time averaged 1 hour 57 minutes and blood loss
      averaged 360 ml. The average time to complete physeal closure was 28 weeks. An
      incomplete bony physeal bridge, apparent at an average 11 weeks, may impart
      earlier stability. Thirty-eight cases had followup averaging 3 years 6 months. At
      most recent evaluation, according to the Harris hip rating system, 35 hips had
      excellent ratings, 1 had a good rating, and 2 had fair ratings. Six patients were
      identified with major postoperative complications, including 1 case each of
      segmental avascular necrosis, chondrolysis, femoral neck fracture,
      subtrochanteric hip fracture, bilateral progressive coxa vara deformities
      requiring corrective osteotomies, and a unilateral progressive coxa vara
      deformity. The senior author (TLS) currently uses a fluoroscopically guided
      percutaneous lateral approach, a cannulated reaming system, and freeze-dried
      irradiated cortical allograft. The procedure promotes premature physeal closure.
      Allograft epiphysiodesis is an alternative operating technique for treating
      patients with a slipped capital femoral epiphysis.

PMID- 8542715
TI  - Screw fixation of Grade III slipped capital femoral epiphysis.
AB  - From 1987 to 1992, 161 children were treated at The Children's Hospital of
      Philadelphia for slipped capital femoral epiphysis. Of these, 23 patients (23
      hips) had Grade III slips (> 50%). Fixation was achieved by 1 or 2 screws in all
      patients. Twenty-one of 23 patients were available for followup (average
      followup, 2.8 years). Four slips were acute, 11 were acute-on-chronic, and 6 were
      chronic. At the most recent followup, radiographs were taken and a Harris Hip
      Score was assigned for each patient. Stabilization without progression of slip at
      followup was achieved in all patients. Screw placement was satisfactory per the
      criteria of Stambough in all patients. Four children (19%) had major
      complications: Three (1 acute slip and 2 acute-on-chronic slips) had avascular
      necrosis of the femoral head; One (chronic slip) had chondrolysis. There were no
      immediate postoperative complications. The mean Harris Hip Score for these 4
      patients was 85 points, versus a mean score of 94 points for all 21 patients.
      Chronic Grade III slipped capital femoral epiphysis can be treated safely and
      effectively by screw fixation. Five of 6 patients had satisfactory results; the
      only exception had evidence of chondrolysis preoperatively. Acute and acute-on
      chronic Grade III slipped capital femoral epiphyses treated with screw fixation
      are less predictable. In 15 patients, reduction occurred in 9 hips despite
      deliberate avoidance of forceful manipulative maneuvers. Avascular necrosis
      developed in 3 (33%) of these 9 hips. Reduction of the acute component of the
      slip during screw fixation, whether deliberate or not, indicates gross
      instability. It is hypothesized that avascular necrosis may be associated with
      injury to the epiphyseal vasculature occurring at the time of the acute slip.

PMID- 8542716
TI  - The demographics of slipped capital femoral epiphysis. An international
      multicenter study.
AB  - One thousand six hundred thirty children with 1993 slipped capital femoral
      epiphyses were reviewed; 41.2% were girls and 58.8% were boys. There were 47.5%
      white, 24.8% black, 16.9% Amerindian, 7.4% Indonesian-Malay, 2.1% Native
      Australian/Pacific Islands, and 1.3% Indo-Mediterranean children. The diseased
      hip was unilateral in 77.7% and bilateral in 22.3% of the children, and chronic
      in 85.5% and acute in 14.5% of the children. Of the unilateral slips, 40.3%
      involved the right hip and 59.7% the left hip. The child's weight was greater
      than or equal to the ninetieth percentile in 63.2% of the children. The average
      age for the girls and boys was 12 and 13.5 years. The age at diagnosis decreased
      with increasing obesity. The youngest children were the Native Australian/Pacific
      Island children (11.8 years) and the oldest were the white and Indo-Mediterranean
      children (13 years). The Indonesian-Malay and Indo-Mediterranean children were
      the lightest in weight, and the black children the heaviest. The Indo
      Mediterranean children had the highest proportion of boys (90.5%), and the Native
      Australian/Pacific Island children the lowest (50%). The highest percentage of
      bilaterality was in the Native Australian/Pacific Island children (38.2%), and
      the lowest in the Amerindian children (16.5%). The relative racial frequency of
      slipped capital femoral epiphysis compared with the white population was 4.5 for
      the Polynesian, 2.2 for the black, 1.05 for the Amerindian, 0.5 for the
      Indonesian-Malay, and 0.1 for the Indo-Mediterranean children. In children with
      unilateral involvement, the age at presentation was younger for those children in
      whom bilateral disease later developed (12 versus 12.9 years old). In 82% of the
      children with sequential bilateral slips, the second slip was diagnosed within 18
      months of the first slip.

PMID- 8542717
TI  - Single screw fixation for acute and acute-on-chronic slipped capital femoral
      epiphysis.
AB  - Charts and radiographs of 78 patients with slipped capital femoral epiphysis were
      reviewed. During the retrospective study period, 1990 to 1993, 16 patients had
      acute or acute-on-chronic slips; 21 hips were involved. Nine hips were acute and
      12 hips were acute-on-chronic slips. No patient reported endocrinopathy or other
      systemic illness. All hips were fixed with a single 7-mm cannulated screw. No
      attempts were made for reduction. The lateral head-shaft angle (preoperative,
      postoperative, and at followup) was measured as was the position of the screw
      (postoperative and followup). Physeal closure in 19 hips occurred at a mean of
      9.6 months. Two additional patients did not return for followup until 30 and 36
      months after surgery. At closure, there was no significant change in head-shaft
      angle from preoperative position. No cases of avascular necrosis or chondrolysis
      were seen in this series. Seventeen of the 21 hips had an excellent functional
      result. Three hips had a good result and 1 had a poor result. There was a
      tendency for poor pin position and less satisfactory results to be associated. It
      is concluded that single screw fixation is adequate for treating uncomplicated
      acute and acute-on-chronic slipped capital femoral epiphyses.

PMID- 8542718
TI  - Valgus slipped capital femoral epiphysis. Fact or fiction?
AB  - The cases of 2 patients with valgus slipped capital femoral epiphysis are
      presented. Additional imaging studies provide support for true posterolateral
      epiphyseal displacement. Increased femoral anteversion and coxa valga contribute
      to the pathogenesis of valgus slipped capital femoral epiphysis. In situ pin
      fixation is recommended for stable valgus slipped capital femoral epiphysis. The
      importance of valgus slipped capital femoral epiphysis lies in its recognition
      and appropriate screw placement when internal fixation is used. The percutaneous
      technique should be used with caution. A limited open technique is recommended
      when the anterior skin portal is near the femoral neurovascular bundle.

PMID- 8542719
TI  - Treatment of the unstable (acute) slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis, the most common hip disorder in adolescence,
      traditionally has been classified according to symptom duration. An acute slip is
      1 in which there are symptoms for < 3 weeks; for a chronic slip, there are
      symptoms for > 3 weeks. An acute-on-chronic slip is characterized by a
      combination of both with a recent exacerbation of symptoms. This classification
      system is misleading because it does not consider stability. A stable slipped
      capital femoral epiphysis has a good prognosis, but an unstable slip has a
      guarded prognosis. The priorities in treating an unstable (acute) slip are (1) to
      avoid avascular necrosis, (2) to avoid chondrolysis, (3) to prevent further slip,
      and (4) to correct deformity. The last priority, correcting the deformity, is
      associated with a high incidence of complications including avascular necrosis
      and chondrolysis, so manipulative reduction under anesthesia or an acute
      corrective osteotomy is not recommended. To address these priorities in
      treatment, the authors recommend preoperative bed rest to decrease the synovitis
      and intraarticular effusion. Operative stabilization is done in an elective
      fashion once the synovitis has subsided. The technique includes careful patient
      positioning on the fracture table, which may cause an incidental reduction, but
      no attempt is made to do a manipulative reduction. The technique is dependent on
      radiographic control. The femoral head and neck must be well visualized on the
      anteroposterior and lateral intensifier images before the operation is started.
      The slipped capital femoral epiphysis is stabilized with a single central screw,
      and nonweightbearing ambulation with crutches is recommended until a satisfactory
      painless range of motion has returned.

PMID- 8542720
TI  - Update on the surgical pathology of the vulva.
AB  - Recent developments in the surgical pathology of the vulva include updated
      classifications of non-neoplastic epithelial disorders and vulvar intraepithelial
      neoplasias. Several histologic variants of vulvar squamous cell carcinoma (SCC)
      with distinct clinicopathologic features have been described. The concept of
      superficially invasive vulvar SCC continues to be a complex issue. The use of
      standardized surgical pathology reports and checklists are recent developments in
      surgical pathology.

PMID- 8542721
TI  - Surgical pathology of the uterine cervix. Diagnostic problems and controversies.
AB  - Some of the more interesting and controversial issues concerning the pathology of
      the uterine cervix have been addressed in this article. It is hoped that this
      brief overview will serve as a stimulus for the reader to delve into some of
      these topics in greater detail either by critical examination of the literature
      or reporting one's own experience with these unusual tumors. A heightened
      awareness of the aforementioned "tumor-like" lesions may avert a misdiagnosis of
      malignancy with potentially disastrous consequences.

PMID- 8542722
TI  - Advances in endometrial pathology.
AB  - In conclusion, the diagnosis of endometrial pathology is changing rapidly as our
      understanding of the pathogenesis of endometrial lesions expands. Increasingly,
      recognition of new lesions and further subclassification of well-described
      entities will become more important in patient care.

PMID- 8542723
TI  - Myometrial and stromal lesions of the uterus.
AB  - This article is an overview of uterine neoplasms that demonstrate mesenchymal
      differentiation. Major clinical and pathologic features are described, with a
      focus on those lesions that cause diagnostic difficulty. Brief discussions on
      more recent observations made concerning these entities are also included.

PMID- 8542724
TI  - Epithelial neoplasms of the ovary. An update on current concepts.
AB  - New concepts concerning the histologic features of peritoneal implants in serous
      tumors of low malignant potential and their proposed impact on prognosis are
      discussed. Endometrioid tumors of low malignant potential, transitional cell
      carcinoma, and psammocarcinoma are also reviewed.

PMID- 8542725
TI  - New developments in sex cord-stromal and germ cell tumors of the ovary.
AB  - This article examines unusual and recently described neoplasms such as variants
      of Sertoli-Leydig cell tumors, monodermal teratomas, and small cell carcinoma,
      both the hypercalcemic and pulmonic types. Additionally, clues to assist in
      differentiating metastatic from primary tumors of the ovary are discussed.

PMID- 8542726
TI  - Selected vascular lesions of the placenta.
AB  - The double circulation of the placenta results in great diversity in the
      morphologic expression of vascular lesions. Although the etiology and
      pathogenesis of many of these lesions are not completely understood, it is clear
      that some have potentially serious implications for fetal well-being. This
      article focuses on the diagnostic criteria and clinical significance of selected
      placental vascular lesions.

PMID- 8542727
TI  - Gestational trophoblastic disease. New approaches to diagnosis.
AB  - Although considerable progress has been made in the understanding of the biology
      of gestational trophoblastic tumors, future generations will undoubtedly classify
      our current knowledge base as basic. It is our hope that by more precisely
      defining the genetic basis for these diverse lesions, we may be able to develop
      better diagnostic, surveillance, and treatment modalities for affected patients.

PMID- 8542728
TI  - Update on laboratory diagnosis of sexually transmitted diseases.
AB  - Several new techniques for diagnosis of the sexually transmitted diseases
      commonly seen in the United States have been developed during the past decade.
      The rapid, nonculture techniques for direct detection of Chlamydia trachomatis,
      Neisseria gonorrhoeae, and herpes simplex virus are reviewed, and their
      advantages and disadvantages are compared with conventional diagnostic methods.
      In addition, new tests for diagnosis of syphilis, vaginitis, and vaginosis are
      briefly discussed.

PMID- 8542729
TI  - Pathobiology of human papillomavirus.
AB  - Human papillomavirus (HPV) has long been recognized as the etiologic agent of
      skin and genital warts, and only recently has an oncogenic role been attributed
      to the virus. This article discusses the classification, genetics, and
      pathogenesis of HPV. HPV detection, epidemiology of HPV and cervical neoplasia,
      and HPV infections in the genital tract are also reviewed.

PMID- 8542730
TI  - Fine-needle aspiration cytology of the ovary.
AB  - FNA cytology has been shown to be highly accurate in diagnosing malignant tumors.
      In gynecology, an overall accuracy of 94.5% in the differentiation between benign
      and malignant tumors has been reported. Despite many controversial views
      regarding its safety, aspiration cytology has been accepted as an innocuous
      procedure that can be accomplished with minimal discomfort or complications and,
      in association with laparoscopy, assist in the management of ovarian cysts and
      masses. Although FNA cannot be considered the first-hand diagnostic procedure for
      ovarian cancer in postmenopausal patients, it may be extremely helpful in young
      women, even during pregnancy, to safely differentiate functional and other benign
      ovarian cysts from malignant ones. In postmenopausal women, especially those in
      the high risk group for surgical procedures and those undergoing a "second look"
      intervention following radiation or chemotherapy, aspiration cytology may provide
      sufficient information to warrant abandoning unnecessary surgery. During
      laparotomy for suspected unilateral disease, FNA may provide sufficient data
      about the opposite ovary to allow that organ to remain in place, thus preserving
      its function in a young patient. The pathologist must be familiar with the
      cytology of normal pelvic structures and the diagnostic criteria used to
      differentiate benign from malignant lesions, as well as potential diagnostic
      pitfalls, such as interpretation based on very few cells or the absence of
      appropriate clinical information. Although proper classification of ovarian
      masses can be achieved through FNA, the pathologist should be aware of its
      limitations, such as difficulties in differentiating adenomas from non-neoplastic
      cysts, and tumors of low malignant potential from well-differentiated carcinomas.
      Descriptive histologic terminology should be applied, and terms such as
      "suspicious" or "atypical" avoided. The aspirated material may not only be used
      for the diagnosis and classification of ovarian neoplasms, it may also be used
      for DNA analysis, detection of estrogen receptors and other prognostic markers,
      thus providing information regarding biologic behavior of the tumors. Finally, it
      is hoped that aspiration of ovarian lesions routinely detected by sonography, in
      elderly women or those with a strong family history of ovarian cancer, will allow
      the physician to accomplish detection of early ovarian cancer.

PMID- 8542732
TI  - New therapeutic approaches in gynecologic oncology.
AB  - Early-stage epithelial ovarian cancer, although elusive in screening programs, is
      readily controlled by resection and limited duration chemotherapy. Extensive
      cytoreductive surgery and multiagent chemotherapy, now including paclitaxel, show
      significant, although still modest, improvement in the survival of advanced-stage
      epithelial cancer. The role of radiation therapy for intermediate risk and
      advanced-stage endometrial cancer is debatable. Tailored hysterectomy for early
      stage cervical cancer is replacing radiation therapy in many instances, whereas
      advanced cancer is being treated with combination chemoradiation. Smaller, less
      disfiguring procedures are being used successfully for vulvar squamous cell
      cancers and melanomas.

PMID- 8542731
TI  - Immunohistochemical approaches to diagnosis in gynecologic pathology.
AB  - Immunohistochemical techniques have become widely used in gynecologic pathology
      in recent years. This article is divided into sections of major anatomic areas of
      gynecologic interest, and each section discusses specific pathologic questions
      approachable by these studies. A description of reagents, as they apply in each
      case, is also included.

PMID- 8542733
TI  - Diabetes care in South Africa: present and future.

PMID- 8542734
TI  - A force of magical activity: the introduction of insulin treatment in Britain
      1922-1926.
AB  - The discovery of insulin by Banting and Best in 1992 is the subject of many
      papers and one authoritative book (Bliss M. The Discovery of Insulin. Chicago:
      University of Chicago Press, 1982. See also Bliss M. Rewriting medical history:
      Charles Best and the Banting and Best myth. J Med Hist 1993; 48: 253-274.). This
      paper charts the introduction of insulin in England and examines its effects on
      medical practice. Before 1922 there were few effective drugs and only one
      (thyroid extract) which had to be taken continuously. Insulin was radically
      different; it restored weight and vigour and allowed survival in diabetic coma
      and after surgery but was potentially dangerous because of the possibility of
      hypoglycaemia, had to be given by injection, and the dose varied with the amount
      of food and exercise. The immediate questions to be answered after the supply of
      insulin was assured were how could such a powerful drug be kept out of the hands
      of ignorant people (a phrase used by The Times), who would administer it, and who
      would supervise the treatment? Within a year further problems were identified.
      Should the aims of treatment be the same as those in the starvation era? Could
      the diet be liberalized? How much biochemical monitoring was necessary? I set the
      scene by describing how, from Minkowski's announcement (1889) that pancreatectomy
      caused severe diabetes, most clinicians and physiologists believed that the
      pancreas (and specifically the islets of Langerhans) produced an internal
      secretion which controlled carbohydrate metabolism. After Murray's (1891)
      demonstration that myxoedema could be cured by thyroid extract, it was assumed
      that diabetes would soon yield in the same way. Yet by the beginning of the First
      World War most experts were pessimistic about isolating the hypothetical internal
      secretion and had pinned their hopes on starvation treatment. In the decade
      before the introduction of insulin the management of diabetes was grim; patients
      were kept in hospital for weeks or months, while their calorie intake and glucose
      excretion was meticulously recorded. They were in the wards of physicians with a
      strong interest in biochemistry whose forte was analysing urine not looking after
      patients. When the Medical Research Council set up a multicentre trial of insulin
      in late 1922 they enrolled the physician biochemists who produced the early
      publications and became the experts. The narrow views and innate conservatism of
      these doctors with the inflexibility of the system in (London) teaching hospitals
      meant that insulin treatment became a straightjacket for many patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8542735
TI  - Diabetic renal disease: the quest for normotension--and beyond.
AB  - Over the past two decades there has been an increasing interest in hypertension
      as a risk factor for diabetic renal disease and in particular for the possibility
      of early antihypertensive intervention. Therefore, it would seem timely to review
      the history of hypertension in diabetes, with special reference to renal disease
      and the need for normotension, in a manner resembling glycaemic control. Elevated
      blood pressure (BP) associated with diabetes mellitus has been recognized since
      the beginning of the century and was initially particularly documented in
      association with the demonstration of the striking histological lesion in
      glomeruli, starting with the observation of Kimmelstiel and Wilson in 1936. These
      patients in many cases also showed hypertension, as confirmed in several
      subsequent reports, very similar to the studies of Kimmelstiel and Wilson.
      However, the development was hampered by the lack of effective antihypertensive
      agents and also by some who believed that elevated BP could be of importance to
      preserve renal function in these individuals. Indeed, it was suggested that
      reduction of BP could mean permanent deterioration in renal function. BP remained
      very high in the standard care of diabetic patients up to the middle 1970s. At
      this time it was documented that elevated BP was very closely related to
      development of diabetic renal disease in Type 1 (insulin-dependent) diabetic
      (IDDM) patients, and studies also showed a correlation between blood pressure and
      rate of progression. This correlation stimulated research in intervention, and
      indeed in the 1980s and 1990s several long-term studies reported that
      antihypertensive treatment can reduce the rate of decline in glomerular
      filtration rate (GFR) from about 12 ml min-1 yr-1 down to about 2 ml min-1 yr-1
      in the most optimistic reports; usually a mean level of 2-5 ml min-1 yr-1 is
      achievable by antihypertensive treatment, in clinical situations where glycaemic
      control often is far from perfect. Many studies have also documented that BP
      starts to rise in the early phase of incipient diabetic nephropathy characterized
      by microalbuminuria. This is a stage with well-preserved GFR and therefore
      probably an ideal stage for intervention in these at risk patients. Many studies,
      in particular those employing angiotensin converting enzyme (ACE) inhibitors
      based on important pathophysiological concepts proposed by Brenner, have shown
      that microalbuminuria can be reduced or stabilized by early antihypertensive
      treatment, just as we see with optimized glycaemic control. ACE inhibitors have
      also been widely used in patients with overt nephropathy and the rate of decline
      in GFR has been reduced considerably.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8542736
TI  - Decreasing incidence of major amputation in diabetic patients: a consequence of a
      multidisciplinary foot care team approach?
AB  - The purpose of this retrospective study was to evaluate the changes in diabetes
      related lower extremity amputations following the implementation of a
      multidisciplinary programme for prevention and treatment of diabetic foot ulcers
      in a 0.2 million population with a 2.4% prevalence of diabetes. All diabetes
      related primary amputations from toe to hip from 1 January 1982 to 31 December
      1993 were included. In 294 diabetic patients, 387 primary major (above the ankle)
      or minor (through or below the ankle) amputations were performed, constituting
      48% of all lower extremity amputations. The annual number of amputations at all
      levels decreased from 38 to 21, equalling a decrease of incidence from 19.1 to
      9.4/100,000 inhabitants (p = 0.001). The incidence of major amputations decreased
      by 78% from 16/1 to 3.6/100,000 inhabitants (p < 0.001). The absolute number of
      amputations with a final level below the ankle showed no increase, but their
      proportion increased from 28 to 53% (p < 0.001) and the reamputation rate
      decreased from 36 to 22% (p < 0.05) between the first and last 3-year period.
      Thus, a substantial long-term decrease in the incidence of major amputations was
      seen as well as a decrease in the total incidence of amputations in diabetic
      patients. Seventy-one per cent of the amputations were precipitated by a foot
      ulcer. These findings indicate that a multidisciplinary approach plays an
      important role to reduce and maintain a low incidence of major amputations in
      diabetic patients.

PMID- 8542737
TI  - The costs of diabetes-related lower extremity amputations in the Netherlands.
AB  - Diabetes mellitus is a common problem in the Netherlands and in the rest of the
      world. A complication seen in association with diabetes is peripheral neuropathy
      which can lead to lower extremity amputation. The purpose of this study is to
      identify the duration of hospital stay and the direct costs associated with
      diabetes-related lower extremity amputations in the Netherlands in 1992. Total
      direct costs included costs associated with hospital stay and the average
      procedure specific costs (surgeons' fees, anaesthetists' fees, and operating room
      fees) for the specific level of amputation. In the Netherlands in 1992, 1575
      hospitalizations for 1810 diabetes-related lower extremity amputations occurred.
      The total number of days in the hospital for the diabetic population was 65,778
      days with a mean of 41.8 days per hospitalization. Mean costs associated with
      diabetes-related hospitalizations for amputation were pounds 10,531 (Dfl. 28,433)
      per hospitalization. Persons who underwent multiple amputations during their
      hospitalization stayed in the hospital longer and the costs associated with these
      hospitalizations were higher when compared to hospitalization with a single
      amputation. An increase in length of stay and costs with increasing age and
      higher level of amputation was identified.

PMID- 8542738
TI  - Dead in bed syndrome in young diabetic patients in Norway.
AB  - The incidence of unexplained deaths ('dead in bed syndrome') in Norwegian
      diabetic patients under the age of 40 was investigated during the period 1981
      1990. During this 10-year period there were 240 deaths of all causes in the age
      group 0-39 years. Sixteen of these cases fulfilled the following criteria of the
      'dead in bed syndrome': (1) patient found dead in an undisturbed bed; (2) patient
      observed to be in good health condition the day before; (3) no clinical evidence
      of late complications (except background retinopathy in two cases). Of the 16
      cases ascertained, 10 were males and 6 females. The age range was 7-35 years, and
      the duration of diabetes varied between a few months and 26 years. Autopsy,
      performed in 13 cases, did not reveal any cause of death. Nine patients had been
      using insulin regimens with multiple daily doses. Twelve patients were reported
      as having had frequent episodes of hypoglycaemia, with nocturnal episodes in 10
      cases. There was apparently an increasing incidence of unexplained deaths during
      the study period, with 12 of 16 cases occurring in the years 1988 to 1990.

PMID- 8542739
TI  - Marked hyperinsulinaemia in postmenopausal, healthy Indian (Asian) women.
AB  - The effect of the menopause on insulin metabolism has not received specific
      attention in populations prone to non-insulin-dependent (Type 2) diabetes
      mellitus (NIDDM). Insignificant or slight alterations in insulin levels have been
      reported in postmenopausal women of mainly European ancestry. We thus report on
      the results of a cross-sectional study on the correlates of fasting insulin
      levels in 177 healthy, Indian nurses aged between 25 and 55 years. Fasting
      insulin concentration was markedly higher in the 75 postmenopausal subjects (23.9
      mU I-1) than in the 102 premenopausal women (11.7 mU I-1 (p < 0.0001). Forty
      three (57%) of the postmenopausal subjects had insulin values more than 20 mU I-1
      (the upper normal limit). Stepwise regression analysis on the entire group
      revealed menopause (p < 0.0001), waist:hip ratio (p = 0.0001), apolipoprotein E
      genotype (p = 0.002), and the testosterone: sex hormone binding globulin ratio (p
      = 0.0002) as statistically significant, independent predictors of log insulin
      levels. Age did not account for the difference between premenopausal and
      postmenopausal subjects. The apolipoprotein E genotype emerged as a significant
      correlate of insulin levels, only in postmenopausal women: epsilon 3/3, 26.3 mU I
      1; epsilon 3/4, 51.8 mU I-1 (p = 0.0007). Hyperinsulinaemic postmenopausal
      subjects had higher fasting glucose levels than normoinsulinemic nurses (p =
      0.03), but glycosylated haemoglobin and fructosamine values were all within the
      normal range. Thus fasting hyperinsulinaemia was marked and common among a group
      of healthy, postmenopausal Indian nurses below the age of 55 years, suggesting
      that the menopausal transition may permit or provoke insulin resistance in this
      susceptible population.

PMID- 8542740
TI  - Fetal growth and insulin resistance in adult life: role of plasma triglyceride
      and non-esterified fatty acids.
AB  - Reduced fetal growth is associated with insulin resistance and a high prevalence
      of glucose intolerance in adult life. Because babies who are growth retarded have
      elevated levels of triglyceride and non-esterified fatty acids (NEFA), and
      because similar abnormalities are observed in subjects with the insulin
      resistance syndrome, impaired regulation of lipid metabolism could be one of the
      mechanisms explaining the link between reduced fetal growth and insulin
      resistance. We have, therefore, measured fasting plasma triglyceride and NEFA,
      and the insulin-mediated suppression of NEFA during an oral glucose tolerance
      test in 93 men and women aged 50, born in Preston, whose birthweight and body
      size at birth had been recorded. Elevated fasting plasma triglycerides and
      reduced NEFA suppression during the oral glucose tolerance test were associated
      with the male sex, glucose intolerance, central obesity as indicated by a high
      waist to hip ratio and insulin resistance as measured by a short insulin
      tolerance test. However there were no statistically significant relationships
      between the birth measurements and the circulating lipid levels. Moreover in
      regression analyses the relationships between thinness at birth and insulin
      resistance or glucose intolerance in adult life were unaffected by the addition
      of triglyceride or NEFA in the models. These results suggest that the link
      between reduced fetal growth and insulin resistance in the adult is not mediated
      by an abnormal regulation of lipid metabolism.

PMID- 8542741
TI  - Plasma lipid peroxidation and hyperglycaemia: a connection through
      hyperinsulinaemia?
AB  - Increased lipid peroxidation has been commonly observed in diabetic patients as
      compared to control subjects. However, studies on the relationship to metabolic
      control have yielded conflicting results and no data are available on the
      relationship of hyperinsulinaemia to lipid peroxidation. We investigated, in well
      characterized groups of 93 patients with non-insulin-dependent diabetes mellitus,
      22 subjects with impaired glucose tolerance (IGT) and 96 subjects with normal
      glucose tolerance (NGT), the determinants of plasma lipid peroxidation measured
      by plasma thiobarbituric acid reactive substances (TBARS). These were
      significantly higher in subjects with IGT (1.04 +/- 0.48 mumol I-1) and in NIDDM
      patients (1.00 +/- 0.48 mumol I-1) than in those with NGT (0.75 +/- 0.46 mumol I
      1; p < 0.05). The glucose tolerance status was the major determinant of increased
      lipid peroxidation even after controlling for the effects of age, sex, body mass
      index, physical activity, use of alcohol, smoking, and the use of diuretics. In
      regression analyses the major determinants of plasma TBARS were fasting plasma
      glucose, insulin, and apolipoprotein A1 (inversely) levels. To conclude, plasma
      TBARS were increased in impaired glucose tolerance and in diabetes and they were
      related to prevailing plasma glucose and insulin levels, suggesting a role for
      insulin resistance in increased lipid peroxidation process. On the contrary,
      apolipoprotein A1 may have protective effects in this respect.

PMID- 8542742
TI  - Reduced plasma aldosterone concentrations in randomly selected patients with
      insulin-dependent diabetes mellitus.
AB  - Abnormalities of the renin-angiotensin system have been reported in patients with
      diabetes mellitus and with diabetic complications. In this study, plasma
      concentrations of prorenin, renin, and aldosterone were measured in a stratified
      random sample of 110 insulin-dependent (Type 1) diabetic patients attending our
      outpatient clinic. Fifty-four age- and sex-matched control subjects were also
      examined. Plasma prorenin concentration was higher in patients without
      complications than in control subjects when upright (geometric mean (95%
      confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p <
      0.05). There was no difference in plasma prorenin concentration between patients
      without and with microalbuminuria and between patients without and with
      background retinopathy. Plasma renin concentration, both when supine and upright,
      was similar in control subjects, in patients without complications, and in
      patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was
      suppressed in patients without complications in comparison to control subjects
      (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in
      patients with microvascular disease. Plasma potassium was significantly higher in
      patients than in control subjects (mean +/- standard deviation: 4.10 +/- 0.36 vs
      3.89 +/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138
      +/- 4 vs 140 +/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not
      a useful early marker for diabetic microvascular disease. Despite apparently
      normal plasma renin concentrations, plasma aldosterone is suppressed in insulin
      dependent diabetic patients.

PMID- 8542743
TI  - Indications of low sex hormone binding globulin (SHBG) in young females with type
      1 diabetes, and an independent association to microalbuminuria.
AB  - Sex hormone binding globulin (SHBG) is normally decreased during puberty and
      inversely related to insulin resistance. Microalbuminuria is rare before puberty
      in Type 1 diabetes implicating that sex hormones may contribute to its
      development. We investigated SHBG levels in young females with > 5 years of Type
      1 diabetes, and the association to microalbuminuria. Ten diabetic females with,
      and 15 without microalbuminuria, and 17 healthy controls in pubertal stage 4-5
      were compared regarding anthropometric data, fasting serum levels of SHBG,
      testosterone, insulin, insulin-like growth factor-1 (IGF-1), lipids and
      lipoproteins. Multiple regression analyses were performed to study variables with
      independent influences on SHBG and albumin excretion rate (AER), respectively, in
      Type 1 diabetes. SHBG was lower and testosterone/SHBG ratio higher in
      normoalbuminuric females with diabetes than in controls. This was further
      emphasized in diabetic patients with microalbuminuria. IGF-1 was lower in Type 1
      diabetes than in controls, and significantly decreased in microalbuminuric as
      compared to normoalbuminuric diabetic patients. IGF-1 was only correlated to SHBG
      in healthy controls. In Type 1 diabetes, applying stepwise multiple regression
      analysis, insulin dose, BMI, and HbA1c had a significant and independent inverse
      influence on SHBG (r2 = 0.77, p < 0.001). With log AER as the dependent variable,
      low SHBG, low IGF-1, HbA1c, and age added to the regression (r2 = 0.65, p =
      0.004), whereas BMI, insulin dose and blood pressure did not. In conclusion, SHBG
      is decreased in young females with Type 1 diabetes, influenced by increased
      insulin requirements, BMI and HbA1c. In turn, low SHBG seems to be independently
      associated to elevated AER in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542744
TI  - Insulin-like growth factor-I and IGF-I receptors in diabetic patients with
      neuropathy.
AB  - Since a number of animal studies have shown that insulin-like growth I (IGF-I)
      stimulates nerve regeneration, the aim of our study was to evaluate the possible
      relationship between IGF-I and IGF-I receptors in diabetic patients with
      peripheral neuropathy. One hundred and four patients with Type 2 diabetes (57
      with peripheral neuropathy and 47 non-neuropathic) were studied. Controls were 17
      non-diabetic persons. After an overnight fast, blood was taken for IGF-I, IGF-I
      receptors, glucose, HbA1, C-peptide, and insulin. The neuropathy study group had
      significantly lower levels of IGF-I:144.5 ng ml-1 (57.5-363.0, 95% confidence
      limits) compared to controls: 186.2 ng ml-1 (93.3-371.5), p < 0.01, and to
      diabetic patients without neuropathy: 173.7 ng ml-1 (83.1-363.0), p < 0.01. The
      study group also had a lower number of IGF-I receptors per red cell: 22.9 x 10(3)
      (13.08-38.01) vs control subjects: 28.1 x 10(3) (18.62-42.65), p < 0.01, and non
      neuropathic diabetic patients: 26.3 x 10(3) (16.59-41.68), p < 0.01. In diabetic
      subjects there was a positive correlation (r = 0.20, p < 0.05) between IGF-I and
      HbA1, while in the neuropathy group there was a negative correlation between the
      score for nerve dysfunction with the IGF-I (r = -0.39, p < 0.01) and with IGF-I
      receptors (r = -0.34, p < 0.01). We conclude that in diabetic patients with
      peripheral neuropathy there are abnormalities of IGF-I and IGF-I receptors which
      may contribute to impaired neuronal regeneration.

PMID- 8542745
TI  - Differences in preferences between diabetic patients and diabetologists regarding
      quality of care: a matter of continuity and efficiency of care?
AB  - Diabetologists and diabetic patients were asked about their preferences for
      aspects of care which are considered of importance in relation to the quality of
      care. A questionnaire was constructed using the method of pairwise comparison in
      which respondents constantly had to chose between the statements in order to get
      a priority list. Adults with diabetes mellitus (Types 1 and 2) attending
      outpatient departments were asked to fill in the questionnaire. A response rate
      of 97% was recorded (n = 94). Diabetologists received a postal questionnaire and
      the response rate was 65% (n = 126). There was a reasonable agreement between
      both populations and 'effectiveness of care' was ranked the highest. However, the
      patients gave a significant higher ranking to 'continuity of care' and a lower
      ranking to 'efficiency'. Neither the age and sex of the patients nor the duration
      of the disease had any influence on their opinions. Patients who were treated
      with oral medication ranked 'information' higher than patients using insulin, but
      the difference was not significant. A lower level of education and having public
      health insurance were associated with a higher preference for 'continuity'. No
      differences were found regarding age and sex within the diabetologist population.

PMID- 8542747
TI  - Twinning.

PMID- 8542746
TI  - Diabetes care: a guideline to the facilities needed to support internationally
      endorsed standards.

PMID- 8542748
TI  - Alternative medicine: should it be used by children?

PMID- 8542750
TI  - Ecology of neurotoxigenic strains of clostridia.

PMID- 8542751
TI  - Clinical use of botulinum neurotoxins.

PMID- 8542752
TI  - Growth of clostridia and preparation of their neurotoxins.

PMID- 8542753
TI  - Molecular genetics of clostridial neurotoxins.

PMID- 8542754
TI  - Neuroexocytosis.

PMID- 8542755
TI  - Neurospecific binding, internalization, and retrograde axonal transport.

PMID- 8542756
TI  - Quantal neurotransmitter release and the clostridial neurotoxins' targets.

PMID- 8542757
TI  - Intracellular targets and metalloprotease activity of tetanus and botulism
      neurotoxins.

PMID- 8542758
TI  - The present status of tetanus and tetanus vaccination.

PMID- 8542759
TI  - Botulism: the present status of the disease.
AB  - The main form of human botulism throughout the world is the classic foodborne
      intoxication. Would botulism is very rare, and most of the documented cases have
      been found in the United States. While infant botulism remains rare throughout
      the world, it has become the most frequent form of the disease in the United
      States in recent years. On very rare occasions botulism results from growth and
      toxin production in humans other than infants. Botulism occurs in animals with
      much higher frequency. The causative organisms constitute a diverse group of
      clostridia, resulting in nomenclature problems. Human botulism is largely limited
      to toxin types A, B, and E, while type C botulism predominates in avian and
      nonhuman mammalian species. The diagnosis of botulism is made on the basis of the
      neurologic signs and symptoms that it causes in humans and animals. The diagnosis
      is confirmed by tests that identify the toxin and toxigenic organisms in patient
      and food specimens. Treatment includes supportive intensive care and use of
      therapeutic antitoxin.

PMID- 8542760
TI  - Cellular immunology of tetanus toxoid.

PMID- 8542761
TI  - Immunodiagnosis and immunotherapy of tetanus and botulinum neurotoxins.

PMID- 8542762
TI  - [SBG-V--the surgeon facing the 3rd reform stage].

PMID- 8542763
TI  - [Expert discussion group and consensus conference on behalf of the Drug Committee
      of German Medical Community and Saarland Federal Medical Group 12 May 1995.
      Agreement on practical procedures for rapid, safe diagnosis and therapy of "white
      clot" syndrome].

PMID- 8542764
TI  - [What is new in shock research?].

PMID- 8542765
TI  - [New developments in clinical therapy of shock].

PMID- 8542766
TI  - [Possibilities and limits of conservative management of cruciate ligament
      injuries].

PMID- 8542767
TI  - [The "gold standard" in cruciate ligament replacement].

PMID- 8542768
TI  - [Cruciate ligament allograft transplant: a reliable alternative?].

PMID- 8542769
TI  - [Sense and nonsense of cruciate ligament prostheses].

PMID- 8542770
TI  - [Plate osteosynthesis in humerus shaft fracture].

PMID- 8542771
TI  - [Diagnosis and therapy of splenic rupture].

PMID- 8542772
TI  - [The diagnostic value of thoracic computerized tomography in severe thoracic
      trauma].

PMID- 8542773
TI  - [Laparoscopy in treatment of abdominal stab injuries].

PMID- 8542774
TI  - [Traumatic amputation of the thumb. Indications for replantation, technique and
      long-term outcome].

PMID- 8542775
TI  - [Proximal reinsertion in alloplastic replacement of the anterior cruciate
      ligament. Experimental studies of a modified over the top technique].

PMID- 8542776
TI  - [Hip para-articular femoral fracture in total endoprosthesis].

PMID- 8542777
TI  - [Subtalar dislocation].

PMID- 8542778
TI  - [Corrective osteotomies of the foot after compartment syndromes of the tibia].

PMID- 8542779
TI  - [Results of treatment of scar and fistula carcinomas].

PMID- 8542780
TI  - [Iatrogenic nerve injury and microsurgical treatment].

PMID- 8542781
TI  - [Secondary wound closure of skin defects using elastic bands (dynamic secondary
      suture)].

PMID- 8542782
TI  - [Bilateral lesion of the peroneal nerve with lesion of the left-sided median and
      ulnar nerves in multiple osteocartilaginous exostoses].

PMID- 8542783
TI  - [Candida arthritis of the knee joint caused by penetrating injury].

PMID- 8542784
TI  - [Control device for distal tibial unreamed interlocking nailing].

PMID- 8542785
TI  - [Goal directed guidance--a paradigm change. Brief evaluation of management
      courses of the BDC].

PMID- 8542786
TI  - Distribution of Dermatophagoides mite (Acari: Pyroglyphidae) antigens in homes of
      allergic patients in Japan.
AB  - Dust samples collected in 61 homes of patients with mite allergies and 11 homes
      of non-allergic people as controls were examined for antigen levels of
      Dermatophagoides farinae Hughes and Dermatophagoides pteronyssinus (Trouessart)
      to reveal the current distribution of allergenic mites in homes in Japan. Patient
      homes had higher antigen levels than control homes in comforters and pillows but
      not in futons, carpets, tatamis and wooden floors. Samples with antigen levels of
      > or = 10 micrograms m-2 were more frequent in and around summer (approximately
      April-October) than other seasons of the year in most materials and the
      differences between patient and control homes in comforters and pillows observed
      in yearly totals was also observed during this period. Wooden structures showed
      higher antigen levels than concrete structures in comforters, futons, pillows,
      carpets and tatamis in patient homes. Mite contamination in patient homes in
      relation to environmental factors was discussed.

PMID- 8542787
TI  - Cytologic diagnosis of cat scratch disease (CSD) by fine-needle aspiration.
AB  - Cat scratch disease (CSD) is usually a benign, self-limited lymphadenitis,
      characterized by suppurative granulomas. It can, however, produce a wide spectrum
      of clinical symptoms and cytologic changes and be the source of diagnostic
      dilemmas. Identification of pleomorphic bacilli (PB) with silver impregnation
      stains aids in the diagnosis, but this has not been well documented in cytologic
      preparations or in cases without the classic morphologic changes. We reviewed 13
      aspirations from eight patients (aged 13-36 yr) occurring over a 15 mo time
      period, all clinically or cytologically suspicious for CSD. Sites included:
      axilla (6), parotid (3), epitrochlear (1), neck (1), submental (1), and
      intraclavicular (1) nodes. Neoplasia was initially suspected clinically in 38% of
      the cases. All but two patients had cat exposure on subsequent interview. The
      cytologic differential included bacterial abscess and lymphoproliferative
      disorders in 31%. Neither granulomas nor suppurative inflammation were seen in
      all cases. Changes included: granulomas (77%), PMNs (62%), dispersed epithelioid
      histiocytes (46%), and suppurative granulomas (38%). A modified silver stain
      (Modified Steiner, Sigma Diagnostics, St. Louis, MO) was performed on all
      specimens. Silver positive organisms were seen in 69% of cases and were not
      limited to those preparations with suppurative granulomas. Fine-needle aspiration
      biopsy (FNAB) is an effective method for diagnosing CSD despite its heterogeneous
      appearance; and, when combined with clinical information and silver staining, may
      obviate the need for excision.

PMID- 8542788
TI  - Chronic radiation effects: a correlative study of smears and biopsies from the
      cervix and vagina.
AB  - Cervicovaginal smears and biopsies from patients treated with radiotherapy for
      cervical carcinoma were examined morphologically and immunochemically to provide
      information on the tissue derivation of cells characteristic of chronic radiation
      effect in postirradiation smears. In biopsies, stromal changes, such as fibrosis,
      vessel changes, and atypical fibroblasts were most common. Ulceration, leucocytic
      infiltration, multinucleated giant cells, regenerative epithelium, and atypical
      glandular epithelial cells were also present in some specimens. These changes
      were reflected in smears collected from the same patients, where multinucleated
      giant cells, repair cells, and large atypical cells were often present.
      Correlation of smears and biopsies suggest that repair cells are collected from
      areas of epithelial regeneration and glandular radiation atypia. Sampling of
      ulcerative or eroded tissue may produce smears with multinucleated giant cells,
      atypical stromal cells, endothelial cells, and numerous macrophages. Correct
      recognition of these cell types and smear patterns may assist in avoiding false
      positive diagnoses.

PMID- 8542789
TI  - Value of image guided fine-needle aspiration cytology in the diagnosis of
      pancreatic malignancies.
AB  - In the period between 1981-1993, 93 image guided fine-needle aspiration cytology
      (FNAC) of the pancreas were performed on 63 patients suspected of having a
      pancreatic carcinoma. From these, 42 patients were subsequently confirmed to have
      had a pancreatic malignancy by a tissue biopsy. However, FNAC was positive in 29
      cases (69.04%) while seven cases (16.66%) were classified as suspicious. In six
      cases of malignancy (14.28%), cytologically diagnostic material was not sampled
      using FNAC; hence it was considered that FNAC evaluation gave false negative
      results in these cases. As a result of this study it was felt that while a
      cautious approach is necessary in view of certain false negative results, on the
      whole FNAC was a valuable investigation in the diagnosis of pancreatic carcinoma
      with no serious complications in this series. Also, FNAC under imaging assistance
      is a fairly reliable and safe procedure and the false negative results may be
      reduced by repeat aspirations especially in cases when insufficient diagnostic
      material is obtained in a patient clinically suspected of a pancreatic carcinoma.

PMID- 8542790
TI  - Serosal balls detected immunocytochemically in peritoneal lavage obtained during
      surgery.
AB  - Using the immunoperoxidase technique, we studied "serosal balls," which have
      features resembling those of cells from primary and metastatic tumors, and may
      thus complicate cytodiagnosis. Serosal balls were detected in 32 (18%) of 174
      peritoneal washings. The balls consisted of oval clusters of cells in solid
      masses surrounded by flattened cells. The interior of the serosal balls was
      stained green with Papanicolaou method, showing the presence of homogeneous
      amorphous material, sometimes stained in a filamentous pattern. Almost all
      serosal balls were stained immunocytochemically for both keratin and vimentin.
      The interior was stained with antibodies against collagen types I and III.
      Therefore, these balls were fragments of serous membrane, and contained fibrous
      tissue and mesothelial cells.

PMID- 8542791
TI  - p53 protein expression in fine-needle aspirates of breast cancer: an
      immunocytochemical assay for identifying high-grade ductal carcinomas.
AB  - The expression of the p53 gene product was investigated immunocytochemically in a
      series of 51 fine-needle aspiration (FNA) samples of breast carcinomas. Results
      were compared with those obtained by immunocytochemically on paraffin embedded
      tissue sections of the corresponding surgical specimens. Cytological samples
      showed a variable degree of p53 immunoreactivity in 14 tumors (27.6%), all of
      ductal type, while p53 immunoreactive tumor cells were present in tissue sections
      from 15 carcinomas (29.4%). The only discordant case was a signet-ring cell
      carcinoma. Abnormal p53 expression was significantly associated with high nuclear
      grade in ductal carcinomas. No association was seen with tumor size, lymph node
      status, and age of the patient. Detection of p53 altered expression in FNA
      samples of breast carcinoma may play a role in the assessment of tumoral grading
      and is predictive of p53 immunoreactivity in histological specimens.

PMID- 8542792
TI  - Aspiration biopsy cytology of intranodal myofibroblastoma: case report with
      immunocytochemical analysis.
AB  - Intranodal myofibroblastoma (IM) is a recently delineated clinicopathologic
      entity represented by a myofibroblastic proliferation of the lymph node. It
      usually occurs at the groin and presents clinically as a single enlarged lymph
      node. Its clinical behavior is entirely benign and local excision is curative.
      The authors herein report a case of IM diagnosed by aspiration biopsy cytology
      (ABC). The main diagnostic clues to the cytologic diagnosis of this entity as
      well as the differential diagnosis are presented.

PMID- 8542793
TI  - Cytodiagnosis of parvovirus B19 infection from ascites fluid of hydrops fetalis:
      report of a case.
AB  - The cytologic changes in the smears of fetus ascites fluid with parvovirus B19
      infections are described. Cytology revealed the ground-glass appearance of the
      nuclei having a perinuclear halo, and the nuclear chromatin was spread as a thin
      rim around the inclusion. Subsequently, monoclonal antibodies for parvovirus B19
      were applied to identify the specific antigen in the Papanicolaou-destained
      specimens. Positive staining reaction products were found throughout the
      cytoplasm of cells. Similar phenomena were confirmed in paraffin-embedded tissue
      sections of many organs in autopsy materials. It is hoped that recognition of
      those virus-infected cells in the body cavity fluid of the fetus will be helpful
      in making a diagnosis of hydrops fetalis associated with parvovirus B19
      infections of the pregnant woman.

PMID- 8542794
TI  - Primary hepatic lymphoma: report of two cases diagnosed by fine-needle
      aspiration.
AB  - Primary hepatic lymphoma (PHL) is a rare disease which tends to progress slowly
      in the absence of other disorders and remains confined to the liver until late in
      its course. We report two patients with PHL diagnosed by fine-needle aspiration
      (FNA). Histopathologically, PHL can be misdiagnosed as poorly differentiated
      carcinoma or hepatocellular carcinoma. On FNA, cellular smears with artifactual
      grouping of malignant cells may result in similar errors. Since PHL has an
      excellent prognosis and is not usually the working diagnosis in patients who
      present with a solitary liver mass, a high index of suspicion is necessary to
      make the diagnosis. We report two cases of PHL in which the diagnosis of lymphoma
      was rendered on FNA. In one patient, who carried a clinical diagnosis of
      cavernous hemangioma for 18 mo, FNA showed large-cell lymphoma, B-cell type.
      Subsequent extensive workup did not reveal extrahepatic disease. The other
      patient, followed for sclerosing cholangitis, was clinically thought to have
      developed cholangiocarcinoma. FNA revealed high grade lymphoma, B-cell type. We
      present the clinical, radiologic, and pathologic findings and differential
      diagnoses of PHL as well as the various clinical settings in which PHL has been
      described.

PMID- 8542795
TI  - Exfoliative cytology of adenoma malignum (minimal deviation adenocarcinoma) of
      the uterine cervix.
AB  - Cervical scraping smears from two cases of histologically confirmed adenoma
      malignum of the uterine cervix were reviewed. In one case, several irregular
      sheets of benign-appearing glandular cells with slightly enlarged nuclei,
      conspicuous nucleoli, and clear cytoplasm were found. In the other case, in
      addition to sheets of benign-appearing glandular cells, there were clustered
      malignant glandular cells with prominent nucleoli. The sheets of benign-appearing
      glandular cells in both cases displayed wispy cytoplasmic extensions or "tails."
      Cytologic differential diagnosis with other glandular lesions of the cervix such
      as clear cell carcinoma, microglandular hyperplasia, diffuse laminar glandular
      hyperplasia, tubal metaplasia, and well-differentiated invasive or in situ
      adenocarcinoma is briefly discussed.

PMID- 8542796
TI  - Severe eosinophilia and hepatocellular carcinoma: an unusual association.
AB  - Peripheral eosinophilia is an unusual but recognized paraneoplastic manifestation
      of malignant diseases. We report a case of eosinophilia associated with
      hepatocellular carcinoma which is the second case described in English
      literature.

PMID- 8542798
TI  - Ultrafast Papanicolaou stain is not limited to rapid assessments: application to
      permanent fine-needle aspiration smears.
AB  - Ultrafast Papanicolaou (Pap) stain, a 90-second preparation originally designed
      for the immediate assessment of fine-needle aspiration (FNA) smears (Yang and
      Alvarez, Acta Cytol 1995;39:55-60), can also be adapted for permanent FNA smears.
      It involves the addition of three simple steps prior to the conventional Pap
      procedure: the first step is to make the cells appear larger, thus increasing the
      resolution for analysis of cellular details; the second step is to hemolyse the
      background blood, thus unmasking tumor cells; and the third step is to bring out
      the vibrant colors in the cells and the nucleoli, which stain red.

PMID- 8542797
TI  - Diagnosis of Epstein-Barr virus associated nasopharyngeal carcinoma using fine
      needle aspiration biopsy and molecular diagnostics.
AB  - Molecular technology is being utilized increasingly for diagnostic purposes by
      practicing pathologists. Techniques such as Southern blot, in situ hybridization,
      and polymerase chain reaction have recently been introduced to the clinical
      laboratory setting. We describe a case of nasopharyngeal carcinoma that
      highlights the potential utility of DNA technology to secure an accurate
      diagnosis of a fine-needle aspiration biopsy. In this patient, cytologic
      examination of a cervical lymph node aspirate strongly suggested the possibility
      of a nasopharyngeal carcinoma. Needle aspirate material was submitted for
      molecular genetic detection of the Epstein-Barr virus (EBV) genome. Nine
      micrograms of DNA were isolated, and the presence of clonal EBV DNA was detected
      by the Southern blot technique. The presence of clonal EBV supported the
      cytologic diagnosis of nasopharyngeal carcinoma. Subsequent biopsy of a
      nasopharyngeal mass revealed undifferentiated carcinoma, and in situ
      hybridization revealed that EBV was restricted to the malignant epithelial cells.
      This case illustrates how molecular technology can provide new information that
      is useful in diagnostic cytopathology.

PMID- 8542799
TI  - Hormonal cytology: when and why.

PMID- 8542800
TI  - Applications of flow cytometric DNA analysis to diagnostic cytology.
AB  - Flow cytometry is a rapid method for measuring DNA content. Its high sensitivity
      and specificity in detecting transitional cell carcinomas in bladder washings
      should make it a routinely applied adjunct to cytology once universal laboratory
      standards are firmly established. Diagnostic and prognostic information on solid
      tumors can be obtained at least as reliably on fine-needle aspirations as on
      surgically resected specimens. At the present time, the sensitivity of FCM in the
      evaluation of effusions, peritoneal washings, and CSF is relatively low, and
      although in some cases malignant cells in these specimens that are missed by
      conventional cytology are detected by FCM, the number of such cases is small.
      Investigation continues into the application of FCM to the screening of cervical
      specimens.

PMID- 8542801
TI  - Coping with change: adopting a new paradigm.

PMID- 8542802
TI  - On the "Irreducible false negative rate" in cervical cytology.

PMID- 8542803
TI  - Cytologic diagnosis of Schistosoma haematobium in routine cervicovaginal smear
      from an infertile woman.

PMID- 8542804
TI  - Fine-needle aspiration of a case of non-Hodgkin's lymphoma containing signet ring
      cells.

PMID- 8542805
TI  - Can anyone offer some good news about cytology? I think I can, I think I can.

PMID- 8542806
TI  - Cytomorphologic appearances of normal endometrial cells during different phases
      of the menstrual cycle: a cytologic approach to endometrial dating.
AB  - From 1988 to 1992, 156 endometrial cytologic preparations were procured by
      directly brushing hysterectomy specimens from premenopausal women with normal
      endometrium and regular menstruation. These brushing smears were obtained by
      using the cytobrush and/or the endometrial brush. The cytologic findings were
      correlated with histologic endometrial dating. Of these, 56 cases were classified
      as proliferative phase endometrium; 89, secretory phase; and 11, menstrual phase.
      The cytomorphologic features of endometrial glandular and stromal cells at
      different stages of the menstrual cycle are summarized and compared. On the basis
      of the different cytomorphologic features of glandular and stromal cells seen
      during various phases of the cycle, cytologic differentiation between
      proliferative phase and secretory phase endometria can be readily established. It
      appears possible to date the endometrium by direct endometrial brushing
      technique. It is also possible to determine if the glandular and/or stromal cells
      seen in the endocervical smears procured by the cytobrush are normal endometrial
      cells from cytobrush extraction, and are consistent with the date of the
      menstrual cycle, which should be made clear in the cytology report.

PMID- 8542808
TI  - [The perforation of a right-coronary sinus of Valsalva aneurysm into the right
      atrium].
AB  - HISTORY AND CLINICAL FINDINGS: A 58-year-old man [correction of woman] without
      previous cardiac symptoms developed exertional dyspnoea and peripheral oedema
      which markedly increased within a two-week period. Auscultation revealed a 4/6
      5/6 holosystolic and diastolic machinery murmur. EXAMINATIONS: Transthoracic and
      multiplane transoesophageal echocardiography established the diagnosis of a 3 cm
      aneurysm of the right coronary sinus of Valsalva with clearly demarcated rupture
      into the right atrium, with a large left to right shunt shown on colour-Doppler
      echocardiography. These findings were confirmed on cardiac catheterisation. There
      was no sign of coronary heart disease. TREATMENT AND COURSE: At open-heart
      surgery the aneurysm was resected, the defect closed with an autologous
      pericardial patch and the tricuspid valve reconstructed. On follow-up examination
      the result remained excellent and the patient was free of symptoms. CONCLUSION:
      In ruptured aneurysm of the coronary sinus of Valsalva, multiplane
      transoesophageal echocardiography provides exact diagnosis and optimal planning
      of the operative procedure.

PMID- 8542807
TI  - [5-Aminosalicylic acid in the prevention of recurrences of Crohn's disease].
AB  - AIM OF STUDY: To evaluate the efficacy of 5-aminosalicylic acid (5-ASA) in
      preventing recurrences of Crohn's disease. PATIENTS AND METHODS: Between January
      1988 and December 1989 a total of 60 patients (37 men, 23 women, mean age 34.8
      years) were selected in whom the diagnosis of Crohn's disease had been known for
      at least 2 years. A further criterion for inclusion was remission for at least
      one year in patients who had been operated or for one month in the nonoperated
      ones. Furthermore, the latter must have had at least one recurrence during the
      last year. They were in turn assigned to be treated with 5-ASA (2.4 g daily by
      mouth) or not treated (control). The activity and localization of Crohn's disease
      were defined according to the "Crohn's disease activity index" (CDAI) and the
      "laboratory index" (LI), as well as by endoscopy and (or) radiology. The patients
      were examined every 6 months for 4 years. A recurrence was diagnosed if the CDAI
      was more than 150 or had increased to at least 60 points above the initial value
      and the LI was above 100. RESULTS: 29 recurrences were noted, 72.4% within the
      first 2 years. 15 recurrences (46.9%) were in the treated patients and 14 (58.3%)
      among the untreated controls. The Kaplan-Meier curve (statistical comparison of
      the probability of recurrence) showed no significant difference between the two
      groups (P = 0.23): the recurrence rate was the same in the two groups, among the
      patients with or without previous operation and for different primary
      localizations. There were no notable side effects. CONCLUSION: Treatment with 5
      ASA was not found to influence the likelihood of recurrence. Age, duration of the
      disease, primary localization and previous operation were not prognostic factors.

PMID- 8542809
TI  - [Primary plasmacytoma of the lymph node (plasmocytic lymphoma). The differential
      diagnosis of nodal plasma-cell proliferates].
AB  - HISTORY AND CLINICAL FINDINGS: A 60-year-old man was found on routine examination
      to have an enlarged, firm, cervical lymph node. He looked older than his age and
      his general condition was poor. He had no fever, nocturnal sweating or weight
      loss. Further examination revealed no hepatosplenomegaly on palpation, but
      numerous enlarged cervical lymph nodes were palpable. INVESTIGATIONS:
      Histological investigation of a cervical lymph node revealed a marked increase in
      slightly pleomorphic plasma cells with monotypic expression of IgM-kappa.
      Multiple myeloma was excluded on the basis of histological and cytological
      findings in the bone marrow. Serology revealed a mild antibody deficiency
      syndrome (gamma-globulin 7.8%) with signs of acute inflammation and an increase
      in alpha 2-globulin. There was no evidence of a monoclonal gammopathy on
      electrophoresis. A diagnosis of primary nodal plasmacytoma was made. COURSE: As
      the patient was asymptomatic at diagnosis he was not given chemotherapy. There
      was no evidence of tumour progression at follow-up examination two months later.
      His progress will be monitored closely. CONCLUSION: This patient's history is
      consistent with the prognosis generally associated with primary nodal
      plasmacytoma that is much better than that of multiple myeloma.

PMID- 8542811
TI  - [The oral treatment of rosacea with isotretinoin].

PMID- 8542810
TI  - [The neuroleptic malignant syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 22-year-old oligophrenic patient had on several
      occasions over several months been given various neuroleptics (haloperidol,
      benperidol, levomepromazine) for exacerbations of paranoid schizophrenia. For a
      few days before hospitalization he had become quiet and withdrawn, but on the day
      of admission 100 mg chlorprothixene was administered intramuscularly when he had
      become agitated. At admission he was somnolent, his general condition was
      disturbed. He had hyperhidrosis and hypersalivation, as well as tachycardia
      (112/min) with a normal body temperature of 37.8 degrees C. He also exhibited the
      cogwheel phenomenon of the limbs and neck, as well as tremor of the hands. The
      differential diagnosis included inflammatory disease of the brain, sinus
      thrombosis and, especially, malignant neuroleptic syndrome and febrile catatonia.
      INVESTIGATIONS: The activities of creatine kinase (3840 U/l), GOT (75 U/l) and
      GPT (88 U/l) were all increased. Serum myoglobin was 77 micrograms/l. CSF
      contained blood and there was pleocytosis of 50/3 cells. The ECG showed sinus
      tachycardia. EEG, chest radiogram, computed tomography, magnetic resonance
      imaging and cerebral angiography showed no abnormalities. Febrile catatonia could
      not be excluded. TREATMENT AND COURSE: 4 hours after admission the patient began
      to respond with normal orientation. Shortly afterwards he was able to walk a few
      steps, i.e. there was no catatonia. But rigor, tremor, hypersalivation and
      tachycardia persisted and 12 hours later he developed a fever (up to 39.2 degrees
      C). Blood pressure varied with peak pressures up to 190/110 mm Hg. After 2 days
      muscle tone had clearly increased so much that voluntary movement was hardly
      possible. After amantadine administration (200 mg daily) the rigor improved and
      for the first time body temperature became normal again. There were no signs
      pointing to psychotic symptoms. CONCLUSION: Neuroleptic malignant syndrome is
      difficult to distinguish from febrile catatonia and the diagnosis can often only
      be made through the clinical course.

PMID- 8542812
TI  - [Noncardiac chest pain--a disease of the esophagus?].

PMID- 8542813
TI  - [Intraoperative hypothermia].

PMID- 8542815
TI  - [The prophylactic taking of low doses of acetylsalicylic acid and the risk of
      ulcer hemorrhage].

PMID- 8542814
TI  - [High-dosage systemic lysis of a fulminant pulmonary embolism in an
      echocardiographically recognized mobile thrombus of the right heart].

PMID- 8542816
TI  - [Research on Finnish genes].

PMID- 8542817
TI  - [The future of the hereditary diseases in Finland].

PMID- 8542818
TI  - [Looking for Aino].

PMID- 8542819
TI  - [The new perspectives in gene diagnostics].

PMID- 8542821
TI  - [Aspartylglucosaminuria: a point mutation as a cause of mental defect].

PMID- 8542820
TI  - [Linkage and linkage disequilibrium in the Finnish disease heritage].

PMID- 8542822
TI  - [Finnish hereditary amyloidosis: a mutation in the gelsolin gene].

PMID- 8542823
TI  - [Hyperornithinemia and gyrate atrophy: ornithine aminotransferase gene error
      causing a Finnish disease].

PMID- 8542824
TI  - [Choroideremia: in the trace of a new protein family].

PMID- 8542825
TI  - [The role of genes in the type-1 diabetes].

PMID- 8542826
TI  - [Genetic background of the non-insulin dependent diabetes].

PMID- 8542827
TI  - [The Finnish genes of coronary heart disease].

PMID- 8542828
TI  - [Gene errors as a cause of rare and common connective tissue diseases].

PMID- 8542829
TI  - [Genes and multiple sclerosis].

PMID- 8542830
TI  - [From identification of mutation to population screening].

PMID- 8542831
TI  - [From the DNA laboratory to the clinical practice].

PMID- 8542832
TI  - Pattern recognition in equine locomotion.

PMID- 8542833
TI  - Lyme disease: a rare but clinically important disease in the UK.

PMID- 8542834
TI  - Sir Frederick Hobday Memorial Lecture. Some observations on condylar fractures of
      the third metacarpus and third metatarsus in young thoroughbreds.

PMID- 8542835
TI  - The equine embryonic capsule: practical implications of recent research.

PMID- 8542836
TI  - Borrelia burgdorferi infection in UK horses.
AB  - Antibody levels (IgG and IgM) to Borrelia burgdorferi were measured in the sera
      and synovial fluids of UK horses. Western blotting against B. burgdorferi was
      also used on samples from seropositive horses. A low incidence of seropositivity
      was shown in horses from most parts of the UK. This increased in areas that have
      a high incidence of human and canine borreliosis (Norfolk and south coast).
      Leptospira infections of horses did not cause cross reactions in the B.
      burgdorferi ELISA. Most horses did not display clinical signs of Lyme disease. As
      with dogs and man, it is apparent that B. burgdorferi infection occurs in horses
      in the UK but clinical Lyme disease is uncommon.

PMID- 8542837
TI  - Vascular perfusion in horses with chronic laminitis.
AB  - Vascular perfusion casts were used to define and characterise the macroscopic
      perfusion defects present in the distal digit of 11 horses affected by chronic
      laminitis. Five clinically normal horses were used as controls. Based on clinical
      history and clinical status, horses with chronic laminitis were classified as
      being potentially treatable or clinically refractory. Eleven macroscopic vascular
      defects were noted in the casts from horses with laminitis. Four types of lesions
      were identified in the submural laminar circulation, 3 in the coronary bed and 4
      were associated with the solar circulation. Multiple defects were present and a
      definite trend was noted for the perfusion defects to be worse in the casts of
      clinically refractory subjects than in those considered treatable. This
      information suggests that evaluation of circulatory status should add
      significantly to the ability to separate treatable from clinically refractory
      patients. Results also indicated that ventral displacement of the third phalanx
      (sinkers) and compression of the solar vasculature are more prevalent than is
      presently thought.

PMID- 8542838
TI  - Contact area and pressure distribution changes of the equine third carpal bone
      during loading.
AB  - Changes in contact area and pressure distribution with loading were evaluated on
      the proximal articulating surface of the equine third carpal bone using safranin
      O dye staining and pressure sensitive film techniques. A significant increase in
      percentage contact area resulted as the applied load was increased from 3115 to
      9000 N (54.93% +/- 7.99 vs 61.43% +/- 7.37 respectively, P = 0.016). The area in
      contact shifted towards the dorsal aspect of both the radial and intermediate
      facets of the third carpal bone. Changes were also detected in the mean pressure
      under the same loading conditions. There was a significant increase (P < 0.05) in
      the mean pressure on the dorsomedial to dorsolateral aspect of the radial facet
      and the dorsomedial to middle-lateral aspect of the intermediate facet with
      increased loading. A trend towards an increase (P < 0.10) in mean pressure was
      detected on the middle-medial aspect of the radial facet and the middle-medial to
      palmar-lateral aspect of the intermediate facet. There was no significant
      increase (P > 0.05) in mean pressure with an increase in load from 3115 to 9000 N
      at the palmar aspect of either facet. The increase in contact area and mean
      pressure with loading in the most dorsal and dorsomedial aspect of the radial
      facet may explain the large amount of third carpal bone trauma seen in this
      location in racing horses.

PMID- 8542839
TI  - Pharmacodynamics and pharmacokinetics of carprofen in the horse.
AB  - The pharmacokinetics and pharmacodynamics of the nonsteroidal anti-inflammatory
      drug (NSAID) carprofen have been evaluated in 6 horses using a model of acute non
      immune inflammation. Following intravenous administration of 0.7 mg racemic
      carprofen/kg bwt, mean values for pharmacokinetic parameters were 18.1 h
      (elimination half-life); 0.25 l/kg (volume of distribution, Vd[area]); 58.9
      ml/min (clearance); and 57.9 micrograms/ml.h (area under plasma concentration
      time curve). Mean exudate:plasma concentration ratios exceeded 1.0 at all
      sampling times between 2 and 48 h. Swelling at the site of acute inflammation was
      significantly reduced but exudate leucocyte numbers were unchanged. Although
      carprofen produced moderate suppression of serum thromboxane B2 and exudate
      prostaglandin E2 synthesis, these effects were not related to carprofen
      concentrations in plasma or exudate. It was concluded that the anti-oedematous
      action of carprofen was not attributable to inhibition of cyclo-oxygenase.

PMID- 8542840
TI  - Interaction of gentamycin and atracurium in anaesthetised horses.
AB  - Evoked hind limb digital extensor tension (hoof twitch) was maintained at 40% of
      baseline for 1 h by atracurium infusion in 7 horses anaesthetised with halothane.
      After 1 h, atracurium was discontinued and hoof twitch allowed to recover to 75%.
      Atracurium was again given by infusion to maintain 40% twitch for a second hour,
      then 2 mg gentamycin/kg bwt were given i.v. Atracurium infusion was continued for
      a third hour, and then hoof twitch was again allowed to recover spontaneously to
      75%. Gentamycin reduced twitch strength from 40 +/- 1% (mean +/- sem) to 29 +/-
      4% within 7.0 +/- 1.5 min (P = 0.02). Twitch gradually returned to pre-gentamycin
      strength over the course of the next hour. Recovery of hoof twitch from 50% to
      75% took 7.7 +/- 0.7 min for atracurium alone and 11.5 +/- 2.7 min for atracurium
      plus gentamycin (P = 0.03). Recovery from 50% twitch to 75% fade recovery took
      13.8 +/- 0.8 min for atracurium alone and 13.7 +/- 1.2 min for atracurium plus
      gentamycin. At 75% recovery of fade, hoof twitch was 87 +/- 3% for atracurium
      alone and 82 +/- 4% for atracurium plus gentamycin. Reversal of the block with
      edrophonium and subsequent recovery of the horses from anaesthesia were
      uneventful. It was concluded that, although gentamycin did augment the
      neuromuscular blockade of atracurium, the effect was minimal.

PMID- 8542841
TI  - A silver-impregnation and immunocytochemical study of innervation of the distal
      sesamoid bone and its suspensory ligaments in the horse.
AB  - The innervation of the navicular bone (os sesamoideum distale) and its suspensory
      ligaments (ligamenta sesamoidea collateralia) (CSL) or proximal suspensory
      ligament and the ligamentum sesamoideum distale impar or the distal sesamoidean
      impar ligament (DS-impar ligament) was examined using combined anatomical
      techniques of silver impregnation and immunocytochemistry. Silver impregnation
      studies revealed an abundance of nerve fibres present in both the CSL and DS
      impar ligament with the latter having relatively more nerve fibres. These silver
      impregnated nerves coursed parallel to and were associated with the vasculature
      rather than appearing to innervate the vessels. Immunocytochemistry identified
      several sensory-related neuropeptides (calcitonin gene-related peptide (CGRP),
      substance P (SP) and neurokinin A (NKA)) in the nerves of the navicular bone and
      suspensory ligaments. More peptidergic nerves were evident within the synovial
      membrane and loose connective tissue in the dorsal part than in the palmar aspect
      of the CSL. In the CSL along the synovial membrane bordering the distal
      interphalangeal joint, the CGRP, SP and NKA were present in the nerves of vessels
      as well as the intimal layer of the distal interphalangeal joint. In the DS-impar
      ligament, there were many more nerves innervating vessels and the synovial
      membrane between the navicular bone and the third phalanx than were present in
      these structures in the CSL. Nerves with all 3 peptides entered the navicular
      bone via the proximal border and the distal groove to innervate the
      perichondrium, trabeculae and osteons. SP-like nerves also innervated the
      cortical bone underlying the articular cartilage. We suggest that these sensory
      nerve peptides contribute to the pathology of the navicular syndrome. The
      distribution of the nerves in the CSL and the DS-impar ligament could explain the
      clinical effects of local anaesthetics injected into the distal interphalangeal
      joint.

PMID- 8542842
TI  - Cardiorespiratory and metabolic responses to exercise in horses with various
      abnormalities of the upper respiratory tract.
AB  - A standardised incremental exercise test was performed by 9 racehorses with
      idiopathic laryngeal hemiplegia (ILH), 1 horse with maxillary sinus cysts, 1
      horse with epiglottic entrapment, 1 horse with a lesion on the vocal folds, and 1
      horse with pharyngitis. Two of the horses with ILH were retested after
      laryngoplasty and ventriculectomy. The findings were compared with those from 20
      normal racehorses. Heart rate, plasma lactate concentration, arterial blood
      gases, stride frequency, oxygen uptake (VO2) and carbon dioxide production were
      assessed during treadmill exercise on a +10% slope. The group of horses with ILH
      had significantly (P < 0.01) lower peak VO2 values (136 +/- 5 ml/kg/min) than did
      the normal group (154 +/- 3 ml/klg/min). These values represent mean +/- sem.
      Horses with ILH also had significantly higher (P < 0.05) arterial carbon dioxide
      tensions (PaCO2) at 10 m/s and lower speeds at a heart rate of 200 bpm (V200)
      than the normal group. The horse with maxillary sinus cysts had higher PaCO2
      tension at 10 m/s than normal, and abnormal values for several cardiorespiratory
      and metabolic indices. Horses with vocal fold lesions, aryepiglottic entrapment
      and pharyngitis had arterial blood gas and cardiorespiratory indices that were
      similar to those of normal horses. One horse which underwent corrective surgery
      for ILH showed improvements in arterial blood gases and cardiorespiratory indices
      during exercise, while the other horse had values which were the same as, or
      worse than, values before surgery. We conclude that the measurement of arterial
      blood gases and cardiorespiratory indices during treadmill exercise is useful in
      determining the effect on exercise capacity of various upper airway abnormalities
      in racehorses.

PMID- 8542843
TI  - Effects of centrifugation and specimen preparation technique on bronchoalveolar
      lavage analysis in horses.
AB  - Bronchoalveolar lavages (BAL) were performed for 6 healthy horses and 8 horses
      with lower airway diseases (LAD). Total cell and differential counts were
      performed before and after centrifugation and resuspension of the BAL cells in a
      small volume of fluid; there was no difference in the total cell counts, but mast
      cell percentages were significantly (P < 0.05) lower, after centrifugation, in
      the LAD group. The two specimen preparation techniques compared were
      cytocentrifugation and centrifugation on microscope glass covers. For both groups
      of horses, lymphocyte percentages were significantly lower on cytocentrifuged
      specimens; there was also an increase in the other predominant cell type, i.e.
      macrophages in healthy horses and neutrophils in horses with LAD. Lymphocyte
      percentages in healthy horses were higher than those reported in previous
      studies, possibly because of a long-standing exposure to a high-dust environment.
      This study suggests that one centrifugation of the BAL fluid does not affect
      total cell counts, but may cause a decrease in mast cell percentage;
      cytocentrifugation is associated with a consistent decrease in lymphocyte
      percentage.

PMID- 8542844
TI  - Comparison of the stride kinematics of the collected, working, medium and
      extended trot in horses.
AB  - Highly-trained dressage horses were studied to test the hypothesis that stride
      length is altered independently of stride duration in the transitions between the
      collected, working, medium and extended trot. Six well-trained dressage horses
      were filmed at a frame rate of 150 frames/s performing the collected, working,
      medium and extended trots in a sand arena. Temporal, linear and angular data were
      extracted from the films, with 4 strides being analysed for each horse and gait
      type. There were no significant asymmetries between the left and rights limbs or
      diagonals when data from the whole group were pooled, but 3 horses showed
      asymmetries in one or more variables (P < 0.01). Analysis of variance and post
      hoc tests indicated that the speed increased significantly (P < 0.01) from the
      collected (3.20 m/s) to the working (3.61 m/s) to the medium (4.47 m/s) to the
      extended (4.93 m/s) trot. The increases in speed were associated with a
      significant increase in stride length from 250 cm in the collected trot, to 273
      cm in the working trot, 326 cm in the medium trot and 355 cm in the extended trot
      (P < 0.01). The lengthening of the stride was a result of increases between each
      gait type in the over-reach distance, whereas the diagonal distance was
      significantly longer in the extended than the collected trot only (P < 0.01). The
      stride duration tended to decrease as speed increased, and the difference became
      significant between the collected and extended trots (P < 0.01).

PMID- 8542845
TI  - Biokinematic analysis of the Swedish Warmblood riding horse at trot.
AB  - The trotting gait of 4 approved Swedish Warmblood stallions with a mean gait
      score > or = 8.67 (maximum score = 10) at official performance tests was recorded
      by high speed film (approximately 250 frames/sec). Angular patterns and hoof
      trajectories of the left fore and hind limbs were analysed, and presented as mean
      and standard deviation curves. The horses had a mean stride duration of 794.0
      msec (sd 13.7) and the mean diagonal advanced placement was +29.8 msec (sd 7.6).
      The variation in angular patterns between the horses was greatest during the
      swing phase. The trajectory of the hind hoof reference point and the shoulder
      joint angle showed the largest maximum variation (44 and 29% of the total range,
      respectively). The swing phase retraction was much longer in the forelimbs than
      the hind limbs. The shoulder joint angle, fore and hind fetlock joint angles,
      hock joint angle and pelvis inclination decreased during the first part of the
      stance phase and are assumed to be important for weight absorption and storage of
      elastic strain. Kinematic gait analyses have potential in the selection of
      performance horses.

PMID- 8542846
TI  - Pharmacokinetics of ketamine in mules and mammoth asses premedicated with
      xylazine.

PMID- 8542847
TI  - Headshaking associated with Trombicula autumnalis larval infestation in two
      horses.

PMID- 8542848
TI  - Development of reactive arthritis and resistance to erythromycin and rifampin in
      a foal during treatment for Rhodococcus equi pneumonia.

PMID- 8542849
TI  - Pleuropneumonia associated with pulmonary hydatidosis in a horse.

PMID- 8542850
TI  - A 64,X,i(Xq) karyotype in a standardbred filly.

PMID- 8542851
TI  - Quality assurance in research.

PMID- 8542852
TI  - Ventricular performance curves revisited.

PMID- 8542853
TI  - Surface electrodes for physiological measurement and stimulation.

PMID- 8542854
TI  - Comparison of bupivacaine plus buprenorphine with bupivacaine alone by caudal
      blockade for post-operative pain relief after hip and knee arthroplasty.
AB  - In a double-blind, parallel group trial, 15 patients who were given a caudal
      injection of 1.8 mg kg-1 of bupivacaine after induction of anaesthesia, were
      compared with 15 patients in whom 7.2 mg kg-1 of buprenorphine was added to the
      same dose of bupivacaine, prior to knee or hip replacement surgery. The duration
      of analgesia was much longer (mean 606 min vs. 126 min P < 0.001) in those
      receiving added buprenorphine; mean morphine consumption in the first 24 h was
      halved (14 mg vs. 28 mg) and patient satisfaction greatly increased. There were
      no significant differences in the incidence of complications although the group
      which had added buprenorphine had a lower incidence of vomiting.

PMID- 8542855
TI  - Effects of sevoflurane anaesthesia on renal function--duration of administration
      and area under the curve and rate of decrease of serum inorganic fluoride.
AB  - The renal effects of serum inorganic fluoride in sevoflurane anaesthesia were
      studied in 15 patients separated into two groups according to whether anaesthesia
      had lasted more than 7 h. Serum and urine fluoride and beta 2-microglobulin,
      blood urea nitrogen, and serum creatinine were measured during and after
      anaesthesia. The area under the curve of serum fluoride (AUC0-infinity) was
      significantly higher for longer anaesthesia (more than 7 h), but serum fluoride
      at the end of inhalation and the rate of decrease of serum fluoride were similar
      in both groups. Although urine beta 2-microglobulin increased above normal after
      anaesthesia, there were no significant differences between groups. Other indices
      of renal function remained normal. Sevoflurane dose, duration of administration,
      serum fluoride at the end of inhalation, area under the curve and rate of
      decrease of serum fluoride were compared against indices of renal function using
      Spearman's rank correlated index. The only significant correlation was serum
      fluoride at the end of inhalation with serum creatinine. The duration of
      sevoflurane administration and the area under the curve for serum fluoride did
      not affect renal function.

PMID- 8542856
TI  - Anaesthesia for a patient undergoing thoracoscopic assisted trans-hiatal
      oesophagectomy.
AB  - We describe the anaesthetic management of an elderly woman who underwent
      thoracoscopically assisted trans-hiatal oesophagectomy. One-lung ventilation with
      insufflation of carbon dioxide was necessary for adequate surgical access.
      Potential intra-operative problems included hypoxaemia during one-lung
      ventilation, mediastinal shift and inadvertent damage to mediastinal structures.

PMID- 8542858
TI  - Assessment of pain threshold and pain tolerance in women in labour and in the
      early post-partum period by pressure algometry.
AB  - The changes in the pressure pain threshold (PPThr) and pressure pain tolerance
      (PPTol) in 41 parturients have been studied during the active phase of labour and
      in the early post-partum period. The sensitivity to pressure stimuli was examined
      with an electronic pressure algometer placed on the sternum during the interval
      between painful contractions, after extradural analgesia and 24 h after
      childbirth. Prior to extradural analgesia, mean (+/- SD), PPThr and PPTol were
      4.9 +/- 1.6 kg 0.25 cm-2 and 6.9 +/- 1.8 kg 0.25 cm-2, respectively. Similar
      values were recorded 1 h after induction of the extradural block when the pain of
      labour was abolished. At 24 h post-delivery, a significant decrease in both PPThr
      and PPTol was noted (P < 0.001). The lack of influence of extradural analgesia on
      pressure algometry values, and the elevated sensitivity to pain in the early post
      partum period, may be related to the influence of pregnancy and labour on the
      appreciation of pain.

PMID- 8542857
TI  - Adrenaline, cyclic AMP and potassium during general anaesthesia with and without
      epidural analgesia.
AB  - Twenty patients undergoing abdominal surgery under general anaesthesia were
      studied to determine whether beta 2-adrenergic receptor sensitivity and
      adrenaline-induced hypokalaemia are related to preceding adrenergic stress. Half
      of the patients were given epidural analgesia with bupivacaine-adrenaline before
      starting surgery and then a booster dose after 60 min of surgery. The others were
      given only the epidural dose of bupivacaine-adrenaline at 60 min. Despite marked
      increases in the plasma adrenaline concentration after the intra-operative
      epidural dose, there was no decrease in the serum potassium concentration in
      either group. In the patients who received only the 60 min dose, the plasma
      adrenaline concentrations increased more, but the plasma level of cyclic AMP (a
      marker for beta 2-stimulation) increased similarly, which suggests that beta 2
      adrenoceptor responsiveness was somewhat reduced. After the intraoperative
      bupivacaine-adrenaline, the T wave amplitude decreased, but neither U waves nor
      tachycardia developed. In conclusion, adrenergic stimulation during surgery does
      not decrease the serum potassium concentration, regardless of whether the
      surgical stress response has been modified by epidural analgesia. This lack of a
      hypokalaemic effect might be partly due to reduced responsiveness of beta 2
      adrenoceptors to adrenaline.

PMID- 8542859
TI  - A comparative study of ketorolac and diclofenac on post-laparoscopic
      cholecystectomy pain.
AB  - In a randomized, double-blind, placebo-controlled study designed to assess the
      post-operative analgesic efficacy and cost-effectiveness of ketorolac and
      diclofenac 60 ASA I and II patients undergoing laparoscopic cholecystectomy were
      studied. Prior to concluding the operative procedure, an injection (i.m.) of an
      equal volume of either saline 3 mL, ketorolac 60 mg, or diclofenac 75 mg was
      administered. All patients received intravenous morphine via a patient-controlled
      analgesia device (PCA). Post-operative pain intensity was assessed hourly for 4
      h, by recording visual analogue score (VAS) for pain, PCA demands and actual
      morphine administered. PCA demands (mean +/- SD) were greater in the saline
      treatment group (115 +/- 90) when compared with both the ketorolac (42 +/- 44)
      and diclofenac groups (74 +/- 77). Furthermore, the saline treatment group
      received significantly (P < 0.05) more PCA morphine compared with both the
      ketorolac and diclofenac groups (12.2 mg +/- 5.0 vs. 8.6 mg +/- 5.2 vs. 8.9 mg +/
      4.8). Improved pain scores were demonstrated in both the ketorolac and
      diclofenac groups compared with the saline group. PCA demands and post-operative
      morphine requirements were similar in the ketorolac and diclofenac groups.
      Diclofenac has the added advantage, in our institution, of being 60% less
      expensive than ketorolac. We conclude that both ketorolac and diclofenac are
      effective post-operative analgesic drugs. However, economic considerations may
      favour diclofenac administration.

PMID- 8542860
TI  - Effect of injection speed on anaesthetic spread during axillary block using the
      orthogonal two-needle technique.
AB  - One hundred patients undergoing scheduled upper limb orthopaedic surgery were
      studied to determine if the speed of injection of the local anaesthetic solution
      could modify the extent and depth of anaesthesia with the axillary approach to
      the brachial plexus. The blocks were performed using the 'orthogonal two-needle
      technique' in which two needles are positioned on the upper and on the lower
      aspect of the axillary artery, orthogonal to the neurovascular bundle and
      directed towards the fascial compartment containing the radial nerve. The
      patients were randomly assigned to one of three groups to receive one of three
      injection rates (10, 20 and 30 s) (n = 30). In consequence to the results
      obtained in these patients, a further group of 10 patients was a posteriori added
      for whom the injection time for each single shot of anaesthetic solution was
      increased to 1 min. In each group the same mixture and volume of anaesthetic
      solution (a 30 mL mixture of equal parts of 0.5% bupivacaine with adrenaline
      1:200,000 and 2% lignocaine) was injected in two separate boluses of 15 mL each
      through the two positioned needles. A significant association was found between
      the injection rate and the anaesthetic spread for all tested areas with the
      exception of the regions supplied by the median nerve. A greater speed of
      injection was associated with less anaesthetic spread and more frequent block
      failure. A clear association between the anaesthetic spread to all branches of
      the brachial plexus and a slower injection rate of the local anaesthetic was
      found.

PMID- 8542861
TI  - The use of lignocaine to reduce pain on i.v. injection of diluted nalbuphine.
AB  - A randomized, placebo-controlled, double-blind study was conducted on 66 healthy
      patients aged 10-61 years undergoing elective ear, nose and throat surgery to
      assess the incidence and severity of pain associated with intravenous (i.v.)
      injection of diluted nalbuphine HCl given during induction of general
      anaesthesia, and to determine the efficacy of adding lignocaine (2 mg mL-1) to
      nalbuphine to reduce this pain. Injection of saline produced pain of low
      intensity in 15% of patients and a withdrawal response in 3% of patients.
      Injection of nalbuphine mixed with lignocaine produced a significantly higher
      incidence (36%; P < 0.025) and severity (P < 0.025) of pain than saline, but a
      similar number of responses (6%) to pain. The diluted nalbuphine alone produced
      the highest incidence (61%) of pain (P < 0.01 vs. saline, P = NS vs. nalbuphine
      with lignocaine), which was most severe (P < 0.01 vs. saline, P < 0.025 vs.
      nalbuphine with lignocaine), and caused the highest number (27%) of withdrawal
      responses (P < 0.01 vs. saline, P < 0.025 vs. nalbuphine with lignocaine). We
      conclude that diluted nalbuphine 2 mg mL-1 produces pain on i.v. injection into
      peripheral veins, and that this can be significantly reduced by adding lignocaine
      2 mg mL-1 to the solution.

PMID- 8542862
TI  - Comparison of maintenance and recovery characteristics of sevoflurane-nitrous
      oxide and enflurane-nitrous oxide anaesthesia.
AB  - We compared maintenance of anaesthesia and recovery using either sevoflurane or
      enflurane anaesthesia in ASA I-III patients undergoing surgery with an
      anticipated minimum duration of 3 h. Serum fluoride concentrations were also
      measured to assess the potential for renal toxicity. After induction of
      anaesthesia with thiopentone, patients received, for maintenance, either 1.5% end
      tidal sevoflurane (0.73 MAC) with N2O 58% (0.58 MAC) (n = 40) or 1.2% end-tidal
      enflurane (0.7 MAC) with N2O 57% (0.57 MAC) (n = 40). Other drugs administered
      during anaesthesia were similar in all groups. Haemodynamic measurements,
      recovery times, as well as post-operative nausea and vomiting were comparable in
      both groups. The mean peak plasma inorganic fluoride ion concentrations were
      reached 4 h after operation in both groups (27.7 microM L-1 for sevoflurane and
      16.75 microM L-1 for enflurane, P < 0.05) declining 50% within 24 h in both
      groups. A positive correlation (P < 0.05) was found between anaesthetic exposure
      (MAC h) and fluoride concentrations in the two groups. Sevoflurane anaesthesia
      resulted in similar haemodynamic stability, recovery times and post-operative
      side effects as enflurane anaesthesia, but produced significantly greater serum
      fluoride levels.

PMID- 8542863
TI  - The choice of anaesthetic technique for caesarean section does not affect plasma
      beta-endorphin levels in the neonate.
AB  - Umbilical cord blood was collected immediately after parturition in full term
      neonates during Caesarean section under either general or epidural anaesthesia.
      Using a radioimmunoassay technique, beta-endorphin concentrations were measured
      in the plasma of neonates and Apgar scores were evaluated. The mean value of beta
      endorphin was 56.80 +/- 14.35 (pg mL-1) in the general anaesthesia group, and
      53.17 +/- 10.58 (pg mL-1) in the epidural anaesthesia group (N.S.).

PMID- 8542865
TI  - Ketamine and thiopentone in caesarean section.

PMID- 8542864
TI  - Trimetaphan may cause coronary artery spasm.
AB  - We describe a patient in whom possible coronary artery spasm occurred during the
      infusion of trimetaphan. A 55-year-old man with a meningioma was scheduled for
      surgical excision of the tumour. He denied any previous history of chest pain.
      Anaesthesia was maintained with nitrous oxide (67%) in oxygen. The blood pressure
      before commencement of the surgery was 114/70 mmHg, and the pulse rate was 60
      beats min-1. The blood pressure rose to 152/94 mmHg (the pulse rate to 62 beats
      min-1) during incision of the scalp, and intravenous infusion of trimetaphan was
      initiated. The blood pressure gradually decreased to 113/58 mmHg (the pulse rate
      64 beats min-1) 10 min after start of this infusion, and premature ventricular
      contractions were evident on the electrocardiogram. Trimetaphan was withheld, and
      lignocaine was given intravenously. The premature ventricular contractions
      disappeared but ST segments were elevated. Glyceryl trinitrate was then infused
      intravenously. The ST segments remained elevated for 5 min, were depressed for 2
      min and finally became isoelectric. There were no wide swings in blood pressure
      or pulse rate during the event. Post-operative laboratory examination revealed no
      evidence of myocardial infarction. Recovery of the patient was uneventful.

PMID- 8542866
TI  - Advances in antithrombotic drug therapy for coronary artery disease.
AB  - Compounds which inhibit the coagulation cascade and antagonize platelet function
      are fundamental to the successful treatment of acute coronary syndromes. In a
      high proportion of patients with acute myocardial infarction, unstable angina, or
      sudden cardiac death, the acute ischaemic event is precipitated by intracoronary
      thrombus. Occlusive or non-occlusive thrombi have been found in the majority of
      cases, either in vivo or at autopsy. Aspirin and unfractionated heparin have been
      the cornerstones of antithrombotic therapy in such patients for the past decade,
      but while their benefits have been convincingly demonstrated, there are
      significant pharmacokinetic, pharmacodynamic, and clinical limitations. These
      limitations have provided the impetus for the development of newer antithrombotic
      agents with several theoretical advantages over aspirin and heparin. This paper
      has four aims. First it reviews the pathogenesis of intracoronary thrombi in
      acute coronary artery syndromes. Second, it outlines the limitations of current
      antithrombotic therapies. Third, it explores the potential advantages of new
      antithrombin and antiplatelet compounds, which may be understood and classified
      by their mechanism of action (Table 1); how the theoretical advantages may
      translate into clinical practice will be examined. Fourth, the initial clinical
      experience with these new agents will be reviewed briefly.

PMID- 8542867
TI  - Current and future perspectives on antithrombotic therapy of acute myocardial
      infarction.
AB  - Randomised trials of coronary artery patency and mortality support the routine
      use of antithrombotic therapy in all patients with suspected acute myocardial
      infarction. At present, it is unclear whether antiplatelet therapy with aspirin
      alone will suffice or the addition of anticoagulation with either heparin or the
      newer specific thrombin inhibitor, hirudin, will confer a net benefit. The
      ongoing randomised trials, such as GUSTO-2 and TIMI-9, will provide relevant
      information on the use of aspirin plus heparin or aspirin plus hirudin in
      patients treated with thrombolytic therapy. The First American Study of Infarct
      Survival (ASIS-1) will provide data which are relevant to the large population of
      patients who, in the United States, do not receive thrombolytic therapy. When
      these data become available it will be possible for clinicians to make rational
      individual decisions and policy-makers to formulate guidelines concerning optimal
      antithrombotic therapy in myocardial infarction.

PMID- 8542868
TI  - Recombinant hirudin and front-loaded alteplase in acute myocardial infarction:
      final results of a pilot study. HIT-I (hirudin for the improvement of
      thrombolysis).
AB  - Recombinant hirudin, a specific thrombin inhibitor, has been shown to accelerate
      thrombolysis and reduce reocclusions in experimental models. In a pilot trial
      recombinant hirudin (HBW 023) was used as an adjunctive therapy to thrombolysis
      with front-loaded tissue plasminogen activator (t-PA) (100 mg.90 min-1) in 40
      patients with acute myocardial infarction whose duration of symptoms was less
      than 6 h. Patients received a bolus of r-hirudin of 0.07 mg.kg-1 b.w. followed by
      an infusion of 0.05 mg.kg-1.h-1 over 48 h. Complete patency (TIMI grade 3) of the
      infarct-related artery at 30, 60 and 90 min after the start of thrombolytic
      therapy was seen in 38.5%, 64.1% and 71.0% of patients, respectively. After 24-48
      h, 80% of patients had a complete patent infarct vessel. A very early, complete
      and sustained patency (TIMI grade 3 at 60 and 90 min and at 24-48 h) was observed
      in 55% of patients. Reocclusions during the hirudin therapy appeared in six
      (16.1%) patients, two of whom had a PTCA at 90 min. The only reinfarction was
      seen after 6 h; this was successfully treated with additional thrombolysis. Major
      bleedings, mostly related to the invasive procedure, were observed in three
      patients. Spontaneous organ bleedings and intracerebral haemorrhages did not
      occur. There was one in-hospital death due to a late retroperitoneal bleeding. In
      was concluded that, with regard to safety and efficacy, the general feasibility
      of r-hirudin as adjunctive therapy to thrombolysis with front-loaded t-PA, has
      been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542869
TI  - r-hirudin in unstable angina pectoris. Rationale and preliminary data from the
      APT pilot study.
AB  - Therapeutic strategies for patients with unstable angina have been hampered by
      the difficulty in defining a homogenous cohort of patients, and identifying their
      risk for subsequent cardiovascular events. Despite the similarities in
      pathophysiological mechanisms between unstable angina and acute myocardial
      infarction, an analysis of recent trials of thrombolytic therapy in unstable
      angina has failed to reveal evidence of improved clinical outcome. However, both
      aspirin and heparin have shown evidence of benefit and in order to test more
      specific and potent thrombin inhibitors (for example hirudin) it is necessary to
      identify a cohort of patients with a high risk of subsequent cardiac events. This
      small scale pilot study set out to identify patients with unstable angina or non
      Q wave infarction with a high risk of subsequent cardiac events, and to undertake
      a feasibility study of two dose regimens of recombinant hirudin (HPW023). The
      impact on haemostatic parameters and the need for dose adjustment in order to
      achieve the target therapeutic range of activated partial thromboplastin time
      (aPTT) was also assessed. Firstly, the study revealed that it was possible to
      identify a high risk patient population (6/43, 14% had sustained infarction;
      10/43, 23% required emergency or urgent revascularization and 11/43, 26% elective
      revascularization). Secondly, it was possible to achieve stable antithrombin
      regimens with the two selected doses of hirudin (at least 78% of patients were
      within the target range at any of the time points). Haemostatic parameters were
      compared, but larger scale studies are required to establish safety, with a
      reliable estimate of the impact of hirudin on clinical events.

PMID- 8542871
TI  - Controversies in ischaemic heart disease. Conference proceedings. Marbella,
      Spain, 15-17 June 1994.

PMID- 8542870
TI  - Angiographic dose-finding study with r-hirudin (HBW 023) for the improvement of
      thrombolytic therapy with streptokinase (HIT-SK). Interim results.
AB  - To evaluate the efficacy and safety of hirudin, a direct thrombin inhibitor, in
      patients with acute myocardial infarction, a dose-finding, angiography study was
      carried out. After a pilot phase in 10 patients treated with a bolus of 0.1 mg.kg
      1 and a continuous infusion of 0.06 mg.kg-1.h-1 (dose group I), two doses of
      hirudin, bolus 0.2 mg.kg-1.h-1 (DG II), and bolus 0.4 mg.kg-1 with 0.15 mg.kg-1.h
      1 (DG III) were tested and compared with heparin as an adjunct to streptokinase
      and aspirin. This interim analysis was mandatory due to puncture-site related
      bleedings. Early and complete patency was achieved in 30% of 35 heparin patients,
      in 40% of 10 DG I, in 47% of 58 DG II and in 62% of 14 DG III patients. A dose
      response relationship particularly between DG I and DG II, was also observed in
      the anti-thrombotic activity monitored by the aPTT. Apart from the catheter
      related bleedings, there were low rates of serious adverse events.

PMID- 8542872
TI  - Aspirin and myocardial infarction: is one positive study enough?

PMID- 8542873
TI  - Aspirin for primary prevention of coronary disease.

PMID- 8542874
TI  - Regression of atherosclerosis. Does it occur and does it have clinical meaning?

PMID- 8542875
TI  - The use of the internal mammary artery for revascularization of the left anterior
      descending coronary artery.

PMID- 8542876
TI  - The use of autologous saphenous vein grafts for isolated left anterior descending
      coronary artery revascularization.

PMID- 8542877
TI  - Multivessel angioplasty versus bypass surgery. A case for PTCA.

PMID- 8542878
TI  - The management of patients with stable angina and multivessel disease. PTCA or
      coronary bypass surgery?

PMID- 8542879
TI  - Are antianginal drugs effective in post-myocardial infarction secondary
      prevention?

PMID- 8542880
TI  - Are antianginal drugs effective in secondary prevention after myocardial
      infarction?

PMID- 8542881
TI  - Should ACE inhibitors be administered to all patients with acute myocardial
      infarction?

PMID- 8542883
TI  - Should post-infarction asymptomatic ventricular arrhythmias be treated?

PMID- 8542882
TI  - Should ACE inhibitors be administered to all patients after acute myocardial
      infarction? A (cautious) negative response.

PMID- 8542884
TI  - Should post-infarction asymptomatic ventricular arrhythmias be treated? The need
      for caution.

PMID- 8542885
TI  - The changing late prognosis of acute myocardial infarction. Implications and
      mechanisms.

PMID- 8542886
TI  - Has the long-term prognosis of acute myocardial infarction improved with the new
      treatments? The negative outlook.

PMID- 8542887
TI  - Relevance of the pharmacokinetic profile in the treatment of angina pectoris: the
      need for 24 h control.

PMID- 8542888
TI  - Regression or stabilization of atherosclerosis means regression or stabilization
      of what we don't see in the arteriogram.

PMID- 8542890
TI  - Timing of VQ ventilation perfusion scanning.

PMID- 8542889
TI  - Treatment effects on the total ischaemic burden and variables with prognostic
      implications.

PMID- 8542891
TI  - Bone pain palliation with strontium-89 in breast cancer patients with bone
      metastases and refractory bone pain.
AB  - Fifteen patients with breast cancer and skeletal metastases who had bone pain
      refractory to opioid analgesics and who were not eligible for or had not
      responded to local field radiotherapy, were treated with strontium-89. All
      patients had received previous treatment with chemotherapy and radiotherapy for
      bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency
      on analgesics were evaluated before and 4, 8 and 12 weeks after 89Sr
      administration. Patients received 2 MBq/kg (118-148 MBq) of 89Sr by i.v.
      injection. Pain relief and a reduction in analgesic requirements were observed in
      7 of the 15 (47%) patients, with a reduction in the severity score from 34% to
      71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral
      blood cell count was observed in 11 patients: a 15%-66% reduction in white cell
      count and a 14%-75% reduction in platelet count were detected at 12 weeks after
      treatment in these patients. We conclude that 89Sr is effective (47% response
      rate) for bone pain palliation in patients with bone metastases from breast
      cancer. Dependency on opioid analgesics may be reduced in patients with
      refractory bone pain.

PMID- 8542892
TI  - Indium-111 pentetreotide scintigraphy in malignant lymphomas.
AB  - Somatostatin receptor imaging (SRI) was carried out as part of the initial
      staging of 26 patients with histologically proven Hodgkin's (3) and non-Hodgkin's
      (23) lymphoma, and in the assessment of the first treatment's efficacy in seven
      of these patients. Static acquisitions over the whole body were performed 4 and
      24 h after intravenous administration of 150 MBq of indium-111 pentetreotide. SRI
      data were compared with the results of conventional methods (clinical data,
      abdominal and thoracic computed tomography, bone marrow biopsy). Only 50 of the
      86 (58%) confirmed extra-medullary tumour sites were detected by SRI. Twelve
      previously unknown localizations were visualized in seven patients. The Ann Arbor
      clinical stage was modified in only one of them. When tumoral tracer uptake was
      present, a tumour uptake index (TUI) was calculated using two regions of interest
      (one over the tumoral hot spot and one over the shoulder) on 24-h planar images.
      The patients were classified into three groups: high tumour uptake (TUI > 2.5 in
      all tumour sites, group A, six patients), low tumour uptake (1.5 < TUI < 2.5 in
      all tumour sites, group B, 18 patients), and no tumour uptake (group C, two
      patients). The sensitivity of SRI detection was higher in group A (90%) than in
      group B (52%) (P < 0.001). Six weeks after the fourth chemotherapy cycle,
      conventional methods and SRI were concordant in five of seven investigated cases
      (four complete remissions and one residual active thoracic mass showing tracer
      uptake), and discordant in two. SRI demonstrated residual tumoral tracer uptake
      in these two patients, who had previously been considered to be in complete
      remission. In conclusion, SRI does not seem to be reliable for the initial
      staging of lymphomas because of the highly variable and usually low tumoral
      tracer uptake. It may be more useful in the diagnosis of residual masses after
      treatment. However, further studies are needed to assess its specificity.

PMID- 8542893
TI  - The use of thallium-201 in the preoperative detection of breast cancer: an
      adjunct to mammography and ultrasonography.
AB  - Thallium-201 breast scans were performed preoperatively in 72 female patients
      with breast abnormalities detected by mammography and/or ultrasonography (7.5-13
      MHz), in order to differentiate benign from malignant breast disease. Informed
      consent was obtained from each patient. Scintigraphy consisted of anterior and
      oblique planar images of the affected breast and axilla at 10 min and 3 h
      following the injection of 201Tl chloride (110 MBq). All 201Tl scans were
      interpreted without prior knowledge of surgery data. Pathological features of
      breast malignancies, such as tumour size, axillary lymph node metastases, tumour
      grading, lymphatic vascular channel invasion and receptor status, were analysed
      for their association with 201Tl uptake by tumour cells. A total of 76 breast
      lesions were assessed in the study. On final histological diagnosis, there were
      56 malignant tumours, 14 benign nodules (9 fibroadenomas, two cases of adenosis,
      two cases of focal fibrosis and one case of epitheliosis) and six atypical
      lesions (atypical ductal or lobular hyperplasia). Thallium scintigraphy was shown
      to have high accuracy (92%) in detecting breast cancer, better than mammography
      (74%) and ultrasonography (84%). Almost all (51/56) breast cancers showed greater
      201Tl activity than surrounding normal breast tissue while there was no
      significant increase in 201Tl activity above background in all but one (19/20)
      case of non-malignant disease. 201Tl activity within breast tumours, calculated
      as tumour/background (T/B) ratio, ranged between 1.2 and 2.5 with a mean value of
      1.45. In our experience the concentration of thallium in the breast cancer seems
      to be primarily dependent on vascularity and tumour size rather than tumour
      grading, lymphatic/vascular invasion or receptor status. 201Tl scan sensitivity
      was 97% for malignant lesions larger than 1.5 cm (n = 35) and 80% for lesions of
      1.5 cm or less (n = 21); however, five of the eight breast cancers smaller than
      1.0 cm were also detectable by 201Tl scintigraphy, compared with five out of
      seven by mammography. Thallium scintigraphy would not be useful in evaluating the
      axilla for lymph node metastases (sensitivity 27%, specificity 77%).

PMID- 8542894
TI  - Increased accuracy of the carbon-14 D-xylose breath test in detecting small
      intestinal bacterial overgrowth by correction with the gastric emptying rate.
AB  - To date, there is no general agreement as to which test is to be preferred for
      the diagnosis of small-intestinal bacterial overgrowth. The 1-g carbon-14 D
      xylose breath test has been proposed as a very sensitive and specific test for
      the diagnosis of bacterial overgrowth. However, in patients with severe
      gastrointestinal motor dysfunction, the lack of consistent delivery of 14C-D
      xylose to the region of bacterial contamination may result in a "negative"
      result. The aim of this study was to determine whether the accuracy of 14C-D
      xylose breath test for detecting bacterial overgrowth can be increased by
      correction with the gastric emptying rate of 14C-D-xylose. Ten culture-positive
      patients and ten culture-negative controls were included in the study. Small
      intestinal aspirates for bacteriological culture were obtained endoscopically. A
      liquid-phase gastric emptying study was performed simultaneously to assess the
      amount of 14C-D-xylose that entered the small intestine. The results of the
      percentage of expired 14CO2 at 30 min were corrected with the amount of 14C-D
      xylose that entered the small intestine. There were six patients in the culture
      positive group with a 14CO2 concentration above the normal limit. Three out of
      four patients with initially negative results using the uncorrected method proved
      to be positive after correction. All these three patients had prolonged gastric
      emptying of 14C-D-xylose. When compared with cultures of small-intestine
      aspirates, the sensitivity and specificity of the uncorrected 14C-D-xylose breath
      test were 60% and 90%, respectively. In contrast, the sensitivity and specificity
      of the corrected 14C-D-xylose breath test improved to 90% and 100%, respectively.
      In conclusion, using the gastric emptying rate of 14C-D-xylose as a correcting
      factor, we found a higher sensitivity and specificity for the 14C-D-xylose breath
      test in the detection of small-intestinal bacterial overgrowth than were achieved
      with the conventional method.

PMID- 8542896
TI  - Serial indium-111-labelled IgG biodistribution in rat Pneumocystis carinii
      pneumonia: a tool to monitor the course and severity of the infection.
AB  - To study the effect of new therapeutic strategies, we developed an animal model
      to monitor the course and severity of experimental Pneumocystis carinii pneumonia
      (PCP) in rats. P. carinii density scores in Giemsa-stained impression smears were
      used to follow P. carinii load. Indium-111 labelled IgG scintigraphy and
      biodistribution, histology of paraffin-embedded tissue sections, lung/body weight
      (L/B wt) ratio and cell count and differentiation of broncho-alveolar lavage
      (BAL) fluid were used as parameters of host inflammatory response. Statistically
      significant differences in L/B wt ratio, number of neutrophils in BAL fluid, P.
      carinii density score, histological extent of inflammation and 111In-IgG
      accumulation in the lung were seen between the rats sacrificed at various time
      points. 111In-IgG accumulation in the lung correlated well with L/B wt ratio and
      P. carinii density score and correlated moderately with number of neutrophils in
      BAL fluid and with the histological extent of inflammation.

PMID- 8542895
TI  - Gastric emptying of two radiolabelled antacids with simultaneous monitoring of
      gastric pH.
AB  - The aim of this study was to assess the gastric emptying rate of two antacids
      using an scintigraphic technique and simultaneous monitoring of gastric pH in 16
      healthy male volunteers. Ten ml of Talcid (hydrotalcite 1 g) and Maalox (Mg-Al
      hydroxide), with a similar neutralization capacity, were labelled with technetium
      99m using a pyrophosphate bridge. Labelled antacids were given on separate days
      (within 2 weeks), 1 h after a standard meal. Intragastric pH was measured for at
      least 4 h, using ambulatory pH-metry with a dual-crystant antimony catheter.
      Continuous monitoring was started 1 h prior to the meal (baseline) and lasted 3 h
      (post-prandial, post-antacid and final periods). The antacid capacity of labelled
      and unlabelled antacids was similar. The mean percentages of antacids retained in
      the stomach fitted a linear model. The mean half-emptying time of Talcid was 63.9
      +/- 27.9 min, while that of Maalox was 57.3 +/- 23.9 min (P = NS). The recordings
      of gastric pH (mean values of pH for each period) showed a similar profile for
      both antacids. The mean pH (Maalox vs Talcid) was 1.69 vs 2.07 in the baseline
      period, 1.95 vs 1.93 in the post-prandial period, 1.79 vs 1.15 in the post
      antacid period (P = NS) and 0.4 vs 0.52 in the final period (P < 0.05 vs prior
      periods). In conclusion, the gastric emptying of Talcid and Maalox was similar
      and pH profiles were parallel and remained unchanged for the two antacids within
      the first hour of intake. A significant decrease in pH was observed 1 h after
      intake of the antacids, suggesting a possible rebound effect.

PMID- 8542897
TI  - Evaluation of the incorporation of bone grafts used in maxillofacial surgery with
      [18F]fluoride ion and dynamic positron emission tomography.
AB  - This study investigates the incorporation of bone grafts used in maxillofacial
      surgery by means of [18F]fluoride ion and positron emission tomography (PET). It
      considers patients who received pedicle grafts for mandibular reconstruction or
      onlay grafts for alveolar ridge augmentation. Dynamic PET images and arterialized
      venous blood samples were obtained within a 1-h period after i.v. injection of
      [18F]fluoride. Assuming a three-compartment model and applying multilinear least
      squares fitting, bone blood flow (K1) and fluoride influx (Kmlf) were determined.
      Additionally Patlak plot analysis was used to calculate fluoride influx (Kpat).
      In cervical vertebral bodies as the reference region, mean values for flow of K1
      = 0.1162 +/- 0.0396 ml/min/ml and influx of Kmlf = 0.0508 +/- 0.0193 and Kpat =
      0.0385 +/- 0.0102 ml/min/ml were found. Essentially these figures are comparable
      with physiological values in animal and man reported in the literature. Early
      after surgery a significant increase in flow and influx compared to vertebral
      bodies was observed in the regions of osteosyntheses between grafts used for
      reconstruction and recipient bone (K1 = 0.2181, Kmlf = 0.1000 and Kpat = 0.0666
      ml/min/ml) and in onlay grafts (K1 = 0.2842, Kmlf = 0.1637 and Kpat = 0.0827
      ml/min/ml). At the same time pedicle grafts showed a significant increase in flow
      but not in influx (K1 = 0.2042, Kmlf = 0.0774 and Kpat = 0.0529 ml/min/ml).
      Furthermore Kpat was significantly lower in pedicle grafts than in onlay grafts.
      In follow-up studies a significant decrease in flow occurred in pedicle grafts
      and the regions of osteosyntheses. Moreover the latter showed a significant
      decrease in Kmlf as well. It is concluded that [18F(-)] PET depicted increased
      blood flow and osteoblastic activity in onlay grafts and regions of
      osteosyntheses, indicating bone repair in the graft and adjacent host bone early
      after surgery. For the regions of osteosyntheses the decrease in both parameters
      corresponded to uncomplicated healing. The lack of increased influx, although
      flow was increased in pedicle grafts, most likely indicates that some necrosis
      occurred in these grafts despite patency of anastomoses. It may be concluded that
      [18F(-)] PET provides further insight into the biology of graft incorporation.

PMID- 8542898
TI  - Influence of high and low plasma insulin levels on the uptake of fluorine-18
      fluorodeoxyglucose in myocardium and femoral muscle, assessed by planar imaging.
AB  - The aim of this study was to optimize the metabolic conditions for planar
      myocardial fluorine-18 fluorodeoxyglucose (FDG) imaging. The effects of high and
      low insulin levels during euglycaemic clamping on myocardial and femoral muscle
      FDG uptake were compared since insulin plays a major role in glucose metabolism.
      FDG uptake in 11 patients was studied using planar scintigraphy. Patients were
      studied twice: in the low-dose insulin protocol (LDI), insulin was infused at a
      rate of 20 mU/kg per hour, starting 1 h before FDG administration, while in the
      high-dose insulin protocol (HDI) it was infused at a rate of 100 mU/kg per hour.
      Glucose infusion rate was adjusted according to frequently determined blood
      glucose levels. Somatostatin was infused to block endogenous insulin release.
      Planar images were obtained from the thorax region and femoral muscles. Regions
      of interest were drawn over normal and abnormal myocardial areas (based on
      angiographic and thallium-201 data) and over lung, liver and muscle areas. After
      clamping, insulin levels during LDI and HDI at t = 60 were 30.6 +/- 13.3 and
      129.6 +/- 30.5 mU/l respectively (P < 0.0001). Femoral muscle uptake was
      significantly higher during HDI (P < 0.001). Uptake in normal and abnormal
      myocardial areas did not differ between the two protocols. Heart/lung ratios (NS)
      and heart/liver ratios (P < 0.05) increased during HDI. It may be concluded that
      planar FDG imaging is influenced by plasma insulin levels. The euglycaemic
      hyperinsulinaemic clamp technique, although more demanding, gives an adjustable
      metabolic steady state without significantly altering the FDG uptake patterns in
      normal and abnormal myocardial regions. The image quality of planar FDG images
      improves due to lower background uptake of FDG during clamping with high plasma
      insulin levels.

PMID- 8542899
TI  - Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach
      using the left ventricular cavity and a blood sample as a reference.
AB  - In patients with chronic heart failure increased sympathetic activity is related
      to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine
      ([123I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac
      sympathetic activity, measurement of myocardial [123I]MIBG uptake may be of
      clinical use in determining prognosis or the effect of pharmacological
      intervention in these patients. The aim of the present study was to evaluate a
      new method to quantitate myocardial [123I]MIBG uptake with respect to
      reproducibility and accuracy. Eighteen [123I]MIBG planar and single-photon
      emission tomographic (SPET) studies of patients with chronic heart failure were
      evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left
      ventricular cavity (C) count density ratio and the 123I activity in a blood
      sample. This was performed employing planar LAO images, a single-slice SPET
      method using the midventricular myocardial short-axis slice, and finally a multi
      slice SPET method analysing semi-automatically drawn volumes of interest (VOIs).
      The accuracy of the multi-slice SPET method was verified using a cardiac phantom.
      The planar method was found to be reproducible [intra- and interobserver
      coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but
      the mean MYO/C count density ratio was only 1.31 +/- 0.16 as a consequence of
      overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13,
      representing poor reproducibility. For the multi-slice SPET method IACV was
      0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4 +/- 2.42.
      Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is
      concluded that the multi-slice SPET method using the left ventricular cavity VOI
      and a blood sample as a reference is a reproducible and accurate method for
      assessing myocardial [123I]MIBG uptake.

PMID- 8542900
TI  - Dipyridamole thallium-201 single-photon emission tomography in aortic stenosis:
      gender differences.
AB  - Dipyridamole single-photon emission tomography (SPET) is used for the detection
      of coronary artery disease (CAD) and the method has also been applied in patients
      with aortic stenosis. This study was undertaken to establish the gender-specific
      normal limits of thallium-201 distribution in patients with aortic stenosis and
      to apply these normal limits in a larger group of patients with aortic stenosis
      to obtain the sensitivity and specificity for coexisting CAD. A low-dose
      dipyridamole protocol was used (0.56 mg/kg during 4 min). Thallium was injected 2
      min later and tomographic imaging was performed. Following image reconstruction a
      basal, a midventricular and an apical short-axis slice were selected. The highest
      activity in each 6 degree segment was normalised to the maximal activity of each
      slice. The normal uptake for patients with aortic stenosis was obtained from ten
      men and ten women with aortic stenosis and a normal coronary angiography. Eighty
      nine patients were prospectively evaluated. An area reduction of at least 75% in
      a coronary artery was considered to be a significant coronary lesion and was
      found in 57 (64%) patients. With gender-specific curves (-2.5 SD) sensitivity for
      detecting CAD was 100% and specificity was 75% in men, while sensitivity was 61%
      and specificity 64% in women. It is concluded that the gender-specific normal
      distribution of 201Tl uptake in patients with aortic stenosis, using dipyridamole
      SPET, yields a high sensitivity and specificity for coronary artery lesions in
      men but a lower sensitivity and specificity in women with aortic stenosis.

PMID- 8542901
TI  - Stabilisation of high-activity 99mTc-d,l-HMPAO preparations with cobalt chloride
      and their biological behaviour.
AB  - It has been reported that the stability of a 1.11-GBq (30 mCi) technetium-99m d,l
      hexamethyl-propylene amine oxime (HMPAO) preparation can be improved to up to 5 h
      by the addition of 200 micrograms CoCl2.6H2O within 2 min after reconstitution.
      However, it is not clear whether this method is also efficient for high-activity
      preparations (5.55 GBq) and whether this modified 99mTc-d,l-HMPAO has the same
      biological properties and can safely be used. We have now studied CoCl2
      stabilised 99mTc-d,l-HMPAO preparations containing different amounts of "in
      house" HMPAO ligand and SnCl2 and reconstituted with activities from 1.11 GBq to
      5.55 GBq 99mTc. The characteristics of the generator eluates were also divergent,
      ranging from fresh eluates from a generator eluted less than 2 h previously to 4
      h-old eluates from a generator not eluted during the preceding 72 h. Preparations
      containing up to 5.55 GBq 99mTc and as low as 2 micrograms SnCl2.2H2O can be
      efficiently stabilised for at least 6 h by the addition of CoCl2 shortly after
      reconstitution. Interestingly, it was found that the stabilisation method is not
      efficient if the cobalt ions are added prior to reconstitution of the
      preparation. This implies that the cobalt chloride cannot be incorporated in the
      labelling kit. Also, preparations with amounts of the ligand lower or higher than
      0.5 mg formed the 99mTc-d,l-HMPAO complex with low radiochemical yield or showed
      rapid degradation. Therefore, combination of a subdivision and storage of Ceretec
      kits in fractions (as reported in the literature) is contra-indicated with this
      CoCl2 stabilisation method. CoCl2-stabilised Ceretec kits reconstituted with 5550
      MBq 99mTcO4- and used 4-5 h after preparation retain the diagnostic usefulness of
      the fresh 1110-MBq preparation with regard to leucocyte labelling and brain
      imaging. Although baboon brain uptake of the stabilised preparation was 6%-9%
      lower, this small difference could not be distinguished in the tomographic
      images. The data obtained with both inhouse prepared d,l-HMPAO and Ceretec kits
      suggest that the eluate restrictions recommended by the Ceretec manufacturer can
      be neglected if the preparation is stabilised with Co2+ ions. Studies with 57Co
      spiked CoCl2 added to d,l-HMPAO preparations demonstrated that the Co2+ ions
      clearly interact with the d,l-HMPAO ligand, probably to form one or more
      complexes. From biodistribution studies in mice it became evident that the
      toxicological profile of the Co2+ ions in the presence of d,l-HMPAO should be
      more favourable than that of cobaltous ions. For these reasons, it seems
      justifiable that CoCl2-stabilised 99mTc-d,l-HMPAO preparations should undergo
      rigorous studies to elucidate their clinical usefulness and pharmacological
      safety.

PMID- 8542902
TI  - Fetal dose estimates and the ICRP abdominal dose limit for occupational exposure
      of pregnant staff to technetium-99m and iodine-131 patients.
AB  - The International Commission on Radiological Protection has recently recommended
      a supplementary dose limit of 2 mSv to the abdominal surface of a pregnant member
      of staff in order to provide protection to her fetus comparable to that in
      members of the public, whose annual limit is recommended to be 1 mSv. In order to
      determine whether this apparent attenuation factor of 50% is appropriate for
      nursing and imaging staff exposed to nuclear medicine patients, estimates were
      made of the ratios of the maternal abdominal surface to fetal dose appropriately
      weighted for time, distance and dose rate. Thermoluminescent dosimeter (TLD)
      measurements were made at various depths in an anthropomorphic phantom irradiated
      at different distances by a distributed source of either technetium-99m or iodine
      131 in order to determine the corresponding attenuation factors at the average
      fetal midline depth. Dose estimates were based on these factors and on published
      values of dose rate and exposure times for nursing and imaging staff at these
      distances from the patient. Fetal doses to nursing staff caring for an adult
      99mTc patient were estimated to vary from 86 microSv to 1.6 microSv, with the
      corresponding ratio of the abdominal surface to fetal dose varying from about
      1.8:1 to 1.5:1 as the patient became less dependent on nursing care and the mean
      distance from the patient increased. Fetal doses to imaging staff varied from
      1.12 microSv to 0.17 microSv for three types of 99mTc scan, but the ratio only
      varied from 1.4:1 to 1.3:1. Fetal doses to imaging staff were estimated to be 6.7
      microSv and 9.0 microSv for a whole-body scan of a thyroid cancer patient after
      131I ablation and therapy respectively, and the ratio was 1.3:1 for both types of
      scan. It was concluded that for a pregnant ward nurse or imaging technologist
      exposed to an adult or paediatric patient administered 99mTc or 131I, a dose
      limit of 1.3 mSv to the maternal abdominal surface will restrict their fetal dose
      to 1 mSv. A pregnant imaging technologist should perform no more than six adult
      99mTc studies or one 131I whole-body scan per day, and may have to wear a more
      sensitive personal dosimeter than a film badge.

PMID- 8542903
TI  - Radioiodinated metaiodobenzylguanidine in neuroblastoma: influence of high dose
      on tumour site detection.
AB  - For more than a decade radioiodinated metaiodobenzylguanidine (mIBG) has been
      commonly used for neuroblastoma imaging. The accuracy of this scintigraphic
      method in detecting both primary and secondary tumour sites is crucial when
      evaluating the extent of disease. The aim of our study was to assess the impact
      of high-activity mIBG scintigraphy on neuroblastoma staging. Eighteen scans (TS)
      were obtained in 15 children after a therapeutic dose of iodine-131 mIBG and
      compared to diagnostic mIBG scans (DS) (in eight cases with 131I-mIBG and in ten
      cases with 123I-mIBG). The superiority of TS over DS was confirmed by the overall
      results: a total of 220 lesions were disclosed with TS and 171 with DS. However,
      in only one case did the TS findings, namely skeletal involvement not evidenced
      on corresponding DS, have an impact on clinical staging. In contrast, neither TS
      nor DS detected proven bone involvement in four patients. The dose-related
      sensitivity of mIBG scintigraphy in detecting neuroblastoma tumour sites was
      confirmed. The ultimate impact of high-dose scans on neuroblastoma management,
      however, seems limited.

PMID- 8542904
TI  - A simple and efficient method to remove free radioiodide from *I
      radiopharmaceuticals.
AB  - Removal of free radioiodide from *I-radiopharmaceuticals was easily performed by
      using a pure metallic silver membrane, placed in a screwable holder. Well-known
      radiopharmaceuticals such as 3-iodobenzylguanidine, Hippuran, iomazenil and fatty
      acids were treated successfully, and gave reproducible results. Only a trace of
      free radioiodide (< or = 1%) was left after passing the silver membrane, while
      rest activity due to retention of the radiopharmaceutical on the membrane was
      negligible (2%-5%). This simple and reliable method offers the possibility of
      application as a last purification step in routine productions, in research or in
      a nuclear medicine department's pharmacy.

PMID- 8542905
TI  - Diagnostic approach to reflex sympathetic dystrophy after fracture: radiography
      or bone scintigraphy?
AB  - The aim of this paper was to compare the value of bone scintigraphy and
      radiography in the early diagnosis of post-fracture reflex sympathetic dystrophy
      (RSD). Thirty-seven adult patients with post-fracture RSD (28 in the first and
      nine in the second clinical stage of RSD), as well as seven patients with
      fracture but without RSD (control group), were investigated by radiography and
      bone scintigraphy. All of them were immobilized (duration of immobilization: 4-22
      weeks). In 21 persons three phase bone scintigraphy was performed. The best
      distinction between the control group and the RSD patients was achieved by
      delayed bone scintigrams. The sensitivity (97%), positive predictive value (97%)
      and accuracy (95%) of delayed bone scintigraphy were very high compared to the
      values for radiography, which were 73%, 90% and 70% respectively. Bone
      scintigraphy also displayed higher specificity (86%) and negative predictive
      value (86%) than radiography (57% and 29% respectively). In the first clinical
      stage the difference between the accuracy of bone scintigraphy (97%) and
      radiography (63%) was greater than for the whole group. In the second stage of
      RSD the accuracy of bone scintigraphy (86%) and radiography (81%) was similar.
      Three-phase bone scintigraphy is not necessary for the diagnosis of post-fracture
      RSD: it is sufficient to perform delayed bone scintigraphy. It is concluded that
      bone scintigraphy is to be preferred to radiography for the early diagnosis of
      post-fracture RSD in the first clinical stage. In the second stage the diagnostic
      capabilities of bone scintigraphy and radiography are more comparable.

PMID- 8542907
TI  - Bone-scintigraphy in painful bipartite patella.
AB  - We report the scintigraphic-appearances of painful bipartite patella in 25-year
      old man a 2 1/2 years history of unexplained patellar pain. Painful bipartite
      patella is a rare cause of chronic post-traumatic patellar pain. Bone
      scintigraphy, by demonstrating increased uptake by the painful accessory
      bipartite fragment, appears to be an imaging method of choice in the diagnosis of
      this condition.

PMID- 8542906
TI  - The contribution of nuclear medicine to the patient with infection.
AB  - Nuclear medicine imaging of infection has two major indications: (a) the
      localization of a focus of infection in patients with fever of unknown origin; in
      this context the radio-pharmaceutical should be highly sensitive whereas
      specificity is not so important because subsequent biopsy or morphologically
      based imaging can be performed; (b) the diagnosis of an infection in patients
      with localized symptoms, for example after surgery, when normal anatomy is absent
      or when metal implants prevent computed tomography or magnetic resonance imaging.
      In these latter cases high sensitivity and to an even greater extent high
      specificity are mandatory to guide further clinical management (conservative or
      surgical). All radiopharmaceuticals available to date, such as technetium-99m
      nanocolloids, gallium-67 citrate, indium-111- and 99mTc-labelled white blood
      cells, 99mTc-antigranulocyte antibodies, and 99mTc-or 111In-labelled unspecific
      human immunoglobulin, have different biodistributions and different physical
      characteristics. The absence of physiological uptake in an organ and the
      radiation exposure of a patient are reasons to use different radiopharmaceuticals
      in different clinical situations, adapted to the individual circumstances of the
      patient.

PMID- 8542908
TI  - Recurrent ovarian endodermal sinus tumor: demonstration by computed tomography,
      magnetic resonance imaging, and positron emission tomography.
AB  - We report a case of recurrent endodermal sinus tumor of the ovary that was
      identified and/or clearly depicted by computed tomography, magnetic resonance
      imaging, and positron emission tomography. The potential roles of various imaging
      modalities in the detection of recurrent endodermal sinus tumor are discussed.

PMID- 8542909
TI  - Technetium-99m tetrofosmin and technetium-99m sestamibi imaging of multiple
      metastases from differentiated thyroid carcinoma.
AB  - A 79-year-old male with follicular thyroid carcinoma metastasizing to the lung,
      bone and lymph nodes was subjected to whole-body scintigraphy using technetium
      99m tetrofosmin and 99mTc-sestamibi. Both agents delineated the metastatic
      lesions and the two image qualities were comparable. We believe that 99mTc
      tetrofosmin and 99mTc-sestamibi images may be helpful in localizing metastatic
      foci and substitute for thallium-201 in the follow-up of patients with
      differentiated thyroid carcinoma.

PMID- 8542910
TI  - Getting full value from technetium-99m perfusion tracers.

PMID- 8542911
TI  - High-intensity transient signals: evolution or revolution in understanding
      cerebral embolism?

PMID- 8542912
TI  - Remote cortical dysfunction as a possible cause of subcortical neglect? A
      regional cerebral blood flow study.
AB  - Cortical remote effects of right deep-seated lesions were studied with two
      cerebral blood flow measurement methods (two-dimensional xenon-133 inhalation and
      99mTc HMPAO SPECT) in a population of 13 right-handed stroke patients. A
      neuropsychological battery of tests suitable for assessment of possible visual
      neglect was performed. Neglect was present in 7 cases. A regional cortical
      hypoperfusion was observed in all patients. However, in neglect patients it was
      more extended and involved the right inferior parietal region suggesting a causal
      relationship between cortical dysfunction and neuropsychological deficit. This
      finding supports the model attributing neglect to a unilateral attention-arousal
      defect in a cortico-limbic-reticular loop.

PMID- 8542913
TI  - Patients with low stump pressure and possible pressure fall in the middle
      cerebral artery during carotid surgery may be identified preoperatively by
      transcranial Doppler.
AB  - Although it has now been established that surgery is the best way to treat
      patients with symptomatic tight carotid stenosis, the fact remains that
      perioperative risks are not negligible. Patients with significant contralateral
      stenosis and/or no collateral flow capacity through the anterior communicating
      artery are likely to be at higher risk during surgery. We examined a series of 52
      patients pre- and postoperatively with transcranial Doppler (TCD) and compared
      the results to perioperative stump pressures. Our intention was to find out
      whether the results of the TCD examination of the circle of Willis could be
      correlated to the perioperative stump pressures, and whether TCD gives reliable
      information about the collateral flow. We found relatively high stump pressures
      in patients with potential function of any communicating artery, and in the group
      with no collateral function most patients had low stump pressures. We also found
      that preoperative flow velocity fall in the middle cerebral artery (MCA) on
      compression of the ipsilateral internal carotid artery correlated with
      perioperative stump-pressure indices. However, we were unable to predict stump
      pressures in individual patients by flow velocity measurements in the MCA
      preoperatively.

PMID- 8542914
TI  - Comparison of subcutaneous sumatriptan with usual acute treatments for migraine.
      French Sumatriptan Study Group.
AB  - 246 migraine patients (International Headache Society definition, 1-6 severe
      attacks per month) were randomised into a multicentre, cross-over study comparing
      subcutaneous (s.c.) sumatriptan 6 mg administered by an auto-injector (Glaxo
      device) with usual acute migraine treatments. Patients were treated for 2 months
      or up to 12 attacks, and then crossed over to the alternative treatment for the
      same duration. Usual treatments were: analgesics (including combinations), 49%;
      ergotamine, 24%; NSAIDs 19%; DHE, 7%. Rescue medication was allowed 2 h after the
      first dose. Headache was assessed on a 4-point self-rating scale (0: none, 1:
      mild, 2: moderate, 3: severe). Other migraine symptoms were assessed as present
      or absent. Quality of life was assessed before the study and at the end of each
      treatment period. Two hundred and seventeen patients were eligible for the cross
      over analysis. At 2 h post-dosing, an average of 78% of attacks per patient were
      successfully relieved (grade 3 or 2 to 1 or 0) by s.c. sumatriptan, compared with
      34% for the usual treatments (p < 0.001) and 63% of attacks per patient were
      completely relieved (grade 0) by s.c. sumatriptan compared with 15% for the usual
      treatments (p < 0.001). Sumatriptan-treated patients used rescue medication for
      19% of their attacks, compared to 59% for comparator drugs (p = 0.001). Results
      for patient preference were: s.c. sumatriptan, 85%; usual treatments, 10%; no
      preference, 5% (p < 0.001). Sumatriptan was significantly superior to comparator
      drugs for all other efficacy end-points (p < 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8542915
TI  - Lymphocytapheresis in combination with immunosuppressive drugs for refractory
      myasthenia gravis: two-color flow cytometric analysis of changes in peripheral
      blood lymphocyte subsets.
AB  - We carried out lymphocytapheresis (LCP) in combination with the administration of
      immunosuppressive drugs in patients with myasthenia gravis (MG), who were
      resistant to conventional immunosuppressive therapy, and examined its efficacy
      and effects on peripheral blood lymphocyte subsets. LCP was carried out once a
      week for 1 month (one course, 4 times) using a continuous-flow blood cell
      separator. Immunosuppressive medication (prednisolone or prednisolone and
      azathioprine) was continued during the course of treatment. After LCP, clinical
      improvement was noted in 5 of 6 patients. Anti-AChR antibody titers and the
      number of lymphocytes were significantly reduced in all patients. A significant
      decrease in CD4+CD45RA- (memory) T cell level and significant increase in
      CD4+CD45RA+ (naive) T cell level were also observed. In the patients having good
      response to LCP, follow-up evaluation showed long-term clinical improvements, as
      well as the memory T cell level staying at the decreased level. Our study
      suggests that LCP in combination with the administration of immunosuppressive
      drugs can suppress the disease activity of MG.

PMID- 8542916
TI  - Is haemodynamical compromise a specific cause of border zone brain infarcts
      following cardiac surgery?
AB  - We evaluated the hypothesis that if hypotension or hypoperfusion is a major cause
      of border zone brain infarction, infarcts following cardiac surgery will be
      likely to be located in the vascular border zone areas, whereas cerebral
      perfusion would be lower compared with non-border zone infarcts. Ten of 37
      patients with brain infarction following cardiac surgery had an infarct in one of
      the vascular border zones on CT. Haemodynamical characteristics and clinical
      features did not differ between border zone infarcts and remaining infarct
      subgroups. We conclude that compared with stroke series brain infarcts following
      cardiac surgery are more frequently located in one of the vascular border zone
      areas, but peri-operative haemodynamic compromise alone does not sufficiently
      explain this difference. Other possible mechanisms, such as showers of (micro
      )emboli, should also be considered.

PMID- 8542917
TI  - Gonadal dysfunction in mitochondrial encephalomyopathies.
AB  - To understand endocrine function and to determine which endocrine systems are
      likely to be affected, 6 patients with mitochondrial encephalomyopathies were
      studied. Three patients had myoclonus epilepsy and ragged-red fibers, and the
      other 3 patients had mitochondrial myopathy, encephalopathy, lactic acidosis and
      stroke-like episodes. Clinically, short stature (5/6), amenorrhea (2/3),
      impotency (3/3), and poor development of secondary sexual characteristics (4/6)
      were noted. The endocrinological studies including triiodothyronine,
      tetraiodothyronine, thyrotropin, adrenocorticotropin, cortisol, parathyroid
      hormone and blood sugar were normal. However, there were low serum concentrations
      of estradiol (2), and progesterone (2) in 3 female patients. Two patients (1 man
      and 1 woman) had growth hormone deficiency and 1 had low testosterone level.
      Hypothalamopituitary dysfunction was confirmed after a series of stimulation
      tests. We conclude that patients with mitochondrial encephalomyopathies are
      common to have gonadal dysfunction. Although target organ may play a role,
      hypothalamopituitary lesion may be responsible for this abnormality.

PMID- 8542918
TI  - Autonomic neuropathy in chronic alcoholism: evaluation of cardiovascular,
      pupillary and sympathetic skin responses.
AB  - Autonomic nerve function was evaluated in 30 alcoholics and 30 healthy subjects
      by means of cardiovascular function tests, pupil cycle time (PCT), and
      sympathetic skin responses (SSR). Nutritional status was assessed by
      anthropometric parameters. Autonomic cardiovascular dysfunction was classified as
      early involvement in 5 patients, definite in 8, severe in 6 and atypical in 3.
      PCT was abnormal in 17 alcoholics. The duration of PCT became progressively
      longer as the severity of cardiovascular involvement increased. SSR was absent in
      4 alcoholics in the palm and in 16 in the sole. These findings indicate that
      sympathetic and parasympathetic mediated functions are abnormal in chronic
      alcoholics with a similar frequency, involving different sites of the autonomic
      nervous system under variable patterns. Significant correlations between
      nutritional status and autonomic neuropathy were found.

PMID- 8542919
TI  - How should clinicians choose treatment for preventing stroke when therapeutic
      trials are not available to guide the situation?

PMID- 8542920
TI  - Evaluation of water molecules in the cold-preserved rat liver by proton magnetic
      resonance imaging.
AB  - Hypothermically preserved rat livers were studied with proton magnetic resonance
      imaging (1H-MRI) under proton density-, spin-lattice relaxation time-, spin-spin
      relaxation time- and diffusion-weighted (P-W, T1-W, T2-W and D-W) conditions.
      Relative signal intensities (RSI) of the liver to distilled water in terms of P
      W, T1-W, T2-W and D-W increased time-dependently during 12 h hypothermic (4
      degrees C) preservation with saline, while these parameters did not increase
      during preservation with University of Wisconsin (UW) solution. One-hour Wiggers'
      hypotensive treatment before the harvesting increased the RSIs of P-W, T2-W and D
      W, and the subsequent 12-hour preservation with UW solution did not improve the
      increased RSIs. These results suggest that 1H-MRI has potential application in
      evaluating the biophysical changes of water molecules in the liver graft, which
      were measured by placing the harvested liver in a plastic bag under a magnetic
      field at a low temperature.

PMID- 8542921
TI  - Effect of the combination of human thioredoxin and L-cysteine on ischemia
      reperfusion injury in isolated rat lungs.
AB  - We studied the role of human thioredoxin and L-cysteine in ischemia-reperfusion
      lung injury. Thirty adult Wistar rats were allocated to five groups, according to
      the drug added to the pulmonary artery flush solution before ischemia (groups 1
      and 2: none; group 3: human thioredoxin; group 4: L-cysteine, and group 5: human
      thioredoxin and L-cysteine) and according to the ex vivo ischemic interval at 37
      degrees C (group 1: no ischemia; groups 2-5: 90 min). After ischemia, the lungs
      were reperfused for 60 min with Krebs-Henseleit solution containing 4% bovine
      serum albumin. In nonischemic lungs, the pulmonary arterial pressure, airway
      pressure, wet to dry lung weight ratio and the albumin concentration in
      bronchoalveolar fluid were within normal ranges. In contrast, all parameters of
      ischemic untreated lungs were generally poor. Compared to the ischemic untreated
      lungs, treatment with the combination of human thioredoxin and L-cysteine
      significantly reduced the wet to dry lung weight ratio (group 2: 9.18 +/- 0.25,
      group 5: 7.88 +/- 0.27), and the albumin concentration in the bronchoalveolar
      lavage fluid (group 2: 78.3 +/- 17.1 micrograms/ml, group 5: 24.0 +/- 3.8
      micrograms/ml). No significant improvement was found in pulmonary arterial
      pressure and airway pressure. These results suggested that treatment with human
      thioredoxin (adult T cell leukemia-derived factor) and L-cysteine attenuates
      ischemia-reperfusion injury in isolated rat lungs.

PMID- 8542922
TI  - Effect of octreotide acetate on pancreatic exocrine and endocrine functions after
      pancreatoduodenal resection.
AB  - In view of forecasting the effect of octreotide acetate (Sandostatin) in
      preventing fistula formation after pancreatic surgery, 9 patients, who had
      pancreatoduodenectomy 8-12 days before, underwent a 2-day study. The first day,
      by means of a catheter located in the jejunal loop separately anastomosed to the
      pancreatic remnant, basal and after secretin stimulation pancreatic secretion was
      evaluated. During the 2nd day the possible inhibitory effect of octreotide on
      basal and stimulated secretion was investigated. Under the experimental
      conditions of the study Sandostatin showed little effect on the water and
      bicarbonate increase as stimulated by secretin. A greater hormone inhibitory
      effect on amylase production and pancreatic endocrine function was seen. On the
      basis of these results the use of Sandostatin can hardly be seen as useful in
      preventing fistula formation after pancreatic resection.

PMID- 8542923
TI  - Role of platelet-activating factor antagonism in haemorrhagic shock in pigs.
AB  - This study aimed at evaluating the role of platelet-activating factor (PAF)
      antagonism in haemorrhagic shock in juvenile pigs. The animals were bled to a
      mean arterial pressure of 30 mm Hg which was maintained for 30 min, then they
      were resuscitated using normal saline 50 ml/kg. Seven pigs received BB-882 (a
      potent novel PAF antagonist) 1 mg/kg as bolus during resuscitation followed by
      continuous infusion of 1 mg/kg/h. Seven pigs received only vehicle. The group
      treated with BB-882 had significantly higher central venous pressure, mean
      pulmonary artery pressure and pulmonary capillary wedge pressure. The mean
      arterial pressure and cardiac output were similar in the two groups, while the
      systemic vascular resistance was significantly reduced by the drug. The BB-882
      group had significantly more tachycardia and less arterial pH. Oxygen delivery
      and consumption and lactic acidaemia were similar in the two groups. These
      effects were not attributed to anaerobic metabolism and may indicate that PAF
      antagonism protected against ischaemia and improved the microcirculation in the
      haemorrhagic shock in pigs.

PMID- 8542924
TI  - Hepatic cholesterol 7 alpha-hydroxylase activity and serum 7 alpha-hydroxy
      cholesterol level during liver regeneration after partial hepatectomy in rats.
AB  - Hepatic cholesterol 7 alpha-hydroxylase is a rate-limiting enzyme for bile acid
      synthesis, and we have previously shown that the serum 7 alpha-hydroxycholesterol
      level reflects the enzyme activity in patients with an intact liver. The purpose
      of this study was to evaluate the alterations in hepatic cholesterol 7 alpha
      hydroxylase activity and the serum 7 alpha-hydroxycholesterol level after
      hepatectomy and the correlations between these parameters and liver mass. Hepatic
      cholesterol 7 alpha-hydroxylase activity, the serum 7 alpha-hydroxycholesterol
      level and the remaining liver weight were determined after 70% hepatectomy in
      rats. Cholesterol 7 alpha-hydroxylase activity was decreased on days 1 and 2
      (from 28.3 +/- 3.7 to 8.5 +/- 2.8 and 13.3 +/- 3.6 pmol/min/mg protein,
      respectively), returned to the preoperative level on day 3 (24.7 +/- 2.6
      pmol/min/mg protein) and further elevated thereafter (71.4 +/- 10.9 on day 7 and
      51.3 +/- 6.6 pmol/min/mg protein on day 14). The serum level of 7 alpha
      hydroxycholesterol changed simultaneously with the enzyme activity, and a
      significant correlation between the two parameters was observed (r = 0.915, p <
      0.0001). The correlations between the liver weight and hepatic cholesterol 7
      alpha-hydroxylase activity and serum 7 alpha-hydroxycholesterol level were
      significant (p < 0.01), but the significances disappeared for the period of days
      3-14 (r = 0.424, p = 0.08; r = 0.299, p = 0.228, respectively). In conclusion,
      hepatic cholesterol 7 alpha-hydroxylase activity is suppressed by hepatectomy and
      then activated as the liver regenerates. The serum 7 alpha-hydroxycholesterol
      level is a good parameter of this enzyme activity after partial hepatectomy.

PMID- 8542925
TI  - Inhibition of hepatic regeneration after 70% partial hepatectomy by simultaneous
      resection of the bowel in rats.
AB  - This study was aimed to evaluate bow simultaneous resection of the bowel
      influences hepatic regeneration after partial hepatectomy (HTX). Two hundred and
      sixty-four rats underwent 70% partial HTX, ileocecal resection (ICR), transverse
      colon resection (TR), colon amputation and simulatenous resection of the liver
      and the bowel (HTX+ICR, HTX+TR). Hepatic DNA synthesis was remarkably suppressed
      by simultaneous resection compared with the 70% HTX group (p < 0.01). In
      simultaneous resection groups, delayed enhanced hepatic protein synthesis (HPS)
      was observed after the operation as compared with the 70% HTX group, which showed
      an early postoperative peak of HPS. Postoperative anastomosis leakage occurred
      more frequently and survival rates were significantly lower in simultaneous
      resection groups. Higher plasma endotoxin levels of the portal and the peripheral
      veins were found in simultaneous resection groups as compared with other groups
      (p < 0.01-0.001). This study suggested that simultaneous resection of the bowel
      with partial HTX might inhibit hepatic regeneration and result in the increased
      risk of anastomosis leakage and high surgical mortality rate by increased plasma
      endotoxin levels and delayed enhanced HPS.

PMID- 8542926
TI  - Influence of dextrans on cardiac preservation in an extracorporeal rat heart
      model.
AB  - Despite advances in preservation techniques for thoracic organs, the ischemic
      tolerance of the donor heart is still limited. Recently, a beneficial effect of
      oncotic substances such as dextran was shown in lung transplantation. Clinically,
      only in the University of Wisconsin (UW) solution oncotic substances for the
      prevention of cellular edema are used. Since little is known about the
      perspective value of dextrans in cardiac preservation, we investigated dextrans
      with different molecular weights added to the St. Thomas Hospital solution in an
      experimental working rat heart Langendorff model for functional and histological
      aspects. By comparison of various dextrans with molecular weights of 40,000,
      70,000 and 160,000 daltons, best results were achieved by the addition of 5%
      dextran with the highest molecular weight.

PMID- 8542927
TI  - In vitro sensitivity of post-bone marrow transplantation CFU-GM and BFU-E to TNF
      alpha and IFN-gamma.
AB  - Graft failure remains one of the limitations of successful marrow
      transplantation. T cell-depleted (TCD) bone marrow transplantation (BMT) is
      reported to have a higher incidence of graft failure than unmodified (UM) BMT. In
      most cases of secondary graft failure, no cellular immune mechanism has been
      identified and etiology remains unclear. In an effort to delineate a cytokine
      mediated mechanism of secondary graft failure, we investigated colony-forming
      unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E)
      growth and pattern of inhibition by tumor necrosis factor-alpha (TNF-alpha) and
      gamma-interferon (IFN-gamma) in the early posttransplant period (day 28).
      Gradient-separated bone marrow mononuclear cells (BMMNC) from 38 recipients of
      TCD BMT, 15 recipients of UM BMT, and 23 normal donors (NLD) were plated in
      cultures of semisolid, serum-containing medium with the addition of stem cell
      factor (SCF), erythropoietin (Epo), and granulocyte colony-stimulating factor (G
      CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Three to seven
      times more CFU-GM and BFU-E colonies were cultures from NLD BM-derived BMMNC than
      from BMMNC of recipients of TCD or UM BMT (p = 0.0001). There was no difference
      in colony number between recipients of UM and TCD BMT on day 28 posttransplant,
      however. Under G-CSF culture conditions, CFU-GM colonies from recipients of UM
      and TCD BMT were more susceptible (p < or = 0.05) to suppression by IFN-gamma at
      concentrations of 1 and 100 U/mL than NLD BMMNC-derived colonies. No other
      difference in IFN-gamma inhibition was detected among the three groups. Under G
      CSF and GM-CSF culture conditions, maximal inhibition was obtained at TNF-alpha
      concentrations > 10 ng/mL. Although early posttransplant BMMNC was more sensitive
      to inhibition than NLD-derived BMMNC, overall, no difference in colony growth or
      percent of inhibition induced by TNF-alpha or IFN-gamma was observed between
      recipients of unmodified and T. cell-depleted transplants. In this series, two
      recipients of TCD BM and one recipient of UM BMT developed graft failure; no
      distinct pattern of colony growth or colony inhibition was evident for those
      patients. The optimized in vitro conditions and specific cytokines used in this
      study do not indicate any quantitative or qualitative differences in the
      hematopoietic progenitors present in recipients of unmodified and T cell-depleted
      bone marrow early posttransplant to explain an increased risk of graft failure
      following a T cell-depleted BMT compared to an unmodified BMT.

PMID- 8542928
TI  - Differential effect of type I interferons on hematopoietic progenitor cells:
      failure of interferons to inhibit IL-3-stimulated normal and CML myeloid
      progenitors.
AB  - We observed a differential effect of type I interferons (IFNs) in inhibiting the
      proliferation of various hematopoietic progenitor cell types. Upon stimulation
      with interleukin-3 (IL-3), IFN-alpha and IFN-beta failed to inhibit colony
      formation of myeloid progenitors (day-14 colony-forming units
      granulocyte/macrophage [CFU-GM]) obtained from peripheral blood (PB) and bone
      marrow (BM) of untreated chronic myelogenous leukemia (CML) patients in chronic
      phase even at IFN doses as high as 10,000 U/mL. In contrast, day-7 CFU-GM
      stimulated with granulocyte colony-stimulating factor (G-CSF) and burst-forming
      units-erythroid (BFU-E) were readily inhibited by moderate doses of IFNs. IFN
      resistant myeloid progenitor cells were also detected in normal BM but not in
      normal PB cells. When suboptimal doses of IL-3 were used in clonal progenitor
      cell assays, day-14 CFU-GM were not protected from the inhibitory action of IFN.
      The failure of IFN to inhibit immature myeloid progenitors was confirmed in
      normal and CML cells highly enriched in CD34-expressing cells. Combinations of
      growth factors were required for sufficient colony formation in these cells,
      whereas IL-3 alone provided only an inadequate stimulation, which was further
      inhibited by IFN. In purified CD34+ cells, day-14 CFU-GM were protected from IFN
      mediated inhibition only upon stimulation with stem cell factor (SCF) in
      combination with IL-3 or G-CSF.

PMID- 8542929
TI  - Eilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor
      cells in chronic myeloid leukemia patients.
AB  - We examined the effect of Eilatin, a novel marine product, on the survival of
      human myeloid progenitor cells (CFU-C) isolated from normal individuals and from
      12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous
      leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the
      effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin,
      IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals
      and CML patients in a dose-dependent manner. The percent survival of colony
      forming units from bone marrow (BM) of seven CML patients in chronic phase
      exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or
      Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than
      the percent survival of myeloid progenitors from normal individuals. A 16-hour
      exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients
      in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7)
      M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the
      ability of the cells to proliferate in liquid culture and a reduction in CFU-C
      content. Using fluorescent in situ hybridization (FISH), we evaluated detection
      of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+
      at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+
      cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion
      signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M,
      IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/-
      4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a
      substance isolated from the Red Sea purple tunicate Eudistoma sp., has an
      antileukemic effect against in vitro Ph+ cells and may be used in conjunction
      with currently available agents for ex vivo purging of BM and/or PB of CML
      patients in conjunction with autologous bone marrow transplantation.

PMID- 8542930
TI  - Progression of natural immunity during one-year treatment of residual disease in
      neuroblastoma patients with high doses of interleukin-2 after autologous bone
      marrow transplantation.
AB  - The aim of this work was to monitor the functional and phenotypic variations of
      natural killer (NK) cells in seven children with stage IV neuroblastoma (NB)
      treated with recurrent 5-day cycles of interleukin-2 (IL-2) at a dose of 18 x
      10(6) IU/m2/d by continuous intravenous infusion. All patients who entered the
      study had no detectable disease after hematologic recovery from intensive
      chemotherapy and autologous bone marrow transplantation (ABMT). To evaluate the
      effect of this treatment on tumor relapse, IL-2 immunotherapy was adjusted to
      maintain levels of NK activity above those of age-matched controls (threshold of
      40 lytic units [LU]/10(9) mononuclear cells) during a 1-year period since
      hematologic recovery of ABMT. The levels of NK and endogenous lymphokine
      activated killer (eLAK) cell cytotoxic activities, as well as phenotype
      differentiated lymphocyte counts, were determined from patients' freshly isolated
      peripheral blood mononuclear cells (MNC). Data were analyzed at different points
      between each cycle of IL-2, and before and 36 hours after each infusion. NK and
      eLAK activities significantly increased in response to IL-2. Both cytotoxic
      parameters correlated with the serum levels of the soluble IL-2 receptor (sIL
      2R). IL-2 increased the amounts of NK and T cell subsets but not of B cells. The
      effects of IL-2 were time-dependent. Early cycles of IL-2 preferentially
      increased cell numbers, especially of cells bearing a CD3-/CD16-/CD56+bright and
      CD8+dim phenotype. Conversely, late courses promoted higher cytotoxic effects but
      with a smaller increase in NK and T cell counts; the main NK subset became CD16+,
      and CD8+dim cells remained a minor subset. It is worthy to note that the patient
      who relapsed after completing immunotherapy showed only a slight increase of the
      NK subset in response to IL-2. These results show the feasibility of sustaining
      an increased NK activity during 1 year after ABMT in children with advanced
      neuroblastoma and suggest the occurrence of changes in the functional and
      phenotypic characteristics of the NK cells generated throughout the 1-year
      treatment.

PMID- 8542931
TI  - Proliferation of individual hematopoietic progenitors purified from umbilical
      cord blood.
AB  - In previous studies, we described long-term cultures of subpopulations of CD34+
      cord blood cells that were fractionated using antibodies specific for CD45RA and
      CD71. In the present study, we plated the most primitive CD34+CD45RAlowCD71low
      cells individually and analyzed the proliferation and expansion kinetics of the
      various hematopoietic progenitors included in this subpopulation. The
      proliferation capacity of single progenitors was assessed by the total number of
      cells produced, and their expansion capacity was assessed by the production of
      CD34+ and colony-forming cells. Monolineage progenitors (erythroid, granulocyte,
      and macrophage progenitors) showed the lowest expansion capacity, which
      correlated with a relatively short life span (< 37 days) of the generated
      colonies. Among these cells, erythroid progenitors showed the highest
      proliferative potential. Based on their relative cell content and
      proliferation/expansion capacities, two types of both granulomacrophagic (GM) and
      multipotent (Mix) progenitors were identified. GM progenitors producing colonies
      with > 70% granulocytes had a low expansion capacity and gave rise to colonies
      that were sustained for < 42 days. A second type of GM progenitors, giving rise
      to colonies with > 90% macrophages, had a higher expansion capacity and the
      colonies they produced were sustained for > 72 days. On the other hand, Mix
      progenitors producing colonies with > 70% erythroid cells had a lower expansion
      capacity and life span (< 46 days in culture), than Mix progenitors producing
      colonies with > 90% myeloid cells (life span of > 72 days). These results
      demonstrate, at the single-cell level, a correlation between the type of
      progenitor cell and its expansion capacity. In turn, the expansion capacity of
      the progenitors was correlated with the life span of the colonies produced.
      Furthermore, our results suggest that in cord blood, at least two types of
      bipotential myeloid (GM) progenitors and two types of multipotent (Mix)
      progenitors can be distinguished, that have respectively low and high
      proliferative and expansion capacity.

PMID- 8542932
TI  - Massive ex vivo generation of functional dendritic cells from mobilized CD34+
      blood progenitors for anticancer therapy.
AB  - We report that blood cell autografts, collected by single leukapheresis in cancer
      patients (n = 11) at the time of mobilization of hematopoietic progenitors into
      peripheral blood following anticancer therapy with high-dose cyclophosphamide (HD
      CTX) plus interleukin-3 (IL-3) and granulocyte colony-stimulating factor (G
      CSF/filgrastim), comprise 1.98 +/- 0.39 x 10(5)/kg (mean +/- SE) CD34+
      progenitors of dendritic cells (DCs). This number corresponds to 140-fold more
      progenitors than in a control autograft collected in the steady state. DCs
      derived from mobilized CD34+ cells, morphologically and immunophenotypically
      undistinguishable from skin Langerhans cells and DCs from bone marrow and cord
      blood CD34+ cells, are shown to be powerful stimulators of allogeneic T cell
      proliferation in primary MLR and of autologous HLA-DR-restricted CD4+ T cell
      proliferation in response to presentation of xenogenic antigens. We show that the
      GM-CSF-plus-TNF-alpha-dependent ex vivo generation of DCs from mobilized CD34+
      cells is 2.5-fold enhanced by flk-2/flt-3 ligand or c-kit ligand (stem cell
      factor) and five-fold enhanced by a combination of these growth factors. In
      addition, the optimal serum for the generation of DCs is autologous HD-CTX
      recovery-phase serum rather than fetal calf serum (FCS) or steady-state human
      serum, which are clinically inadequate and ineffective, respectively. In
      practice, the stimulation of CD34+ cells in a blood cell autograft (15.75 +/-
      2.46 x 10(6)/kg) provided by the above four growth factors should permit ex vivo
      generation of approximately 40 x 10(9) DCs in an adult patient. These new
      findings provide advantageous tools for the large-scale generation of DCs that
      are potentially usable for clinical protocols of immunotherapy or vaccination in
      patients undergoing cancer treatment.

PMID- 8542933
TI  - Immunosuppressive therapy in bone marrow aplasia: the stroma functions normally
      to support hematopoiesis.
AB  - In aplastic anemia (AA) patients responsive to antilymphocyte globulin (ALG)
      therapy, abnormalities in both stroma and progenitor cell (PC) pool have been
      described. The relevance of each pathophysiologic defect was characterized in 16
      individuals, and data were compared to results from seven normal volunteers. Bone
      marrow mononuclear cells were split into two fractions. Stromal layers (SL) were
      prepared from the first, and a CD34+ enriched population was obtained by
      immunomagnetic selection from the second. In cross-culture experiments, 1 x 10(4)
      of the latter from patients or controls were seeded on preformed SL, and adhesive
      PC were scored for the formation of blast colonies (CFU-Bl) on day 5 of culture.
      Nonadherent progenitors were recovered and quantitated in a standard clonogenic
      assay (CFU-GM). There were significantly fewer CD34+ cells in the AA group
      (median 0.65%, SD 0.39%, vs. 1.62%, SD 1.4%; p = 0.002). No morphological or
      cytologic differences between normal and aplastic SL were detected. Both equally
      supported the growth of CFU-Bl from normal progenitors (mean 117, SD 20.4, and
      103.1, SD 30.4), while this value was reduced for the aplastic PC (mean 41.06, SD
      42.9; p = 0.0002, exact two-tailed test). Similarly, the AA nonadherent PC had a
      decreased CFU-GM growth (mean 142.6, SD 104.8, vs. mean 361.7; SD 91.3), with a
      lower total clonogenic output (p = 0.0009). We conclude that aplastic stroma
      appropriately supports the growth of normal progenitors, whereas the depressed
      clonogenicity of the corresponsing population derived from AA is unrelated to
      their attachment to SL but intrinsic to the CD34+ cells, whether adherent or not.

PMID- 8542934
TI  - Immunocytochemical analysis of tumor cells in pre- and post-culture peripheral
      blood progenitor cell collections from breast cancer patients.
AB  - We examined peripheral blood progenitor cell (PBPC) collections and CD(34+)
      selected fractions cultured in PIXY321, a fusion protein comprising analog
      interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM
      CSF) domains, for the presence of contaminating tumor cells from 14 patients with
      advanced-stage breast cancer. Five of the 14 (36%) pre-culture PBPC specimens
      contained immunocyto-chemically (ICC)-detectable tumor cells using two different
      cocktails of monoclonal antibodies (mAbs). After 10 days in culture with PIXY321,
      the CD(34+)-selected fractions showed a median 23.6-fold expansion of
      hematopoietic cells. No ICC-positive tumor cells were detected in any post
      culture specimens. We conclude that in vitro expansion of CD(34+)-selected PBPCs
      with PIXY321 can expand hematopoietic cell populations apparently without risk of
      expanding contaminating breast cancer cell populations.

PMID- 8542935
TI  - The novel monoclonal antibody By114 helps detect the early emergence of a
      paroxysmal nocturnal hemoglobinuria clone in aplastic anemia.
AB  - The newly described monoclonal antibody By114 has been used with flow cytometry
      to investigate the status of the 90-kD glycosylphosphatidyl-inositol (GPI)
      anchored component of CD66 (CD66c) on neutrophils from nine patients with
      paroxysmal nocturnal hemoglobinuria (PNH), seven with aplastic anemia/PNH, and 63
      with aplastic anemia (AA) and a negative Ham's test. We have found that By114 is
      a sensitive indicator for recognizing patients with PNH and has helped delineate
      a group of nine patients with aplastic anemia and a negative Ham's test who have
      evidence of a larger PNH clone than indicated by other monoclonal antibodies
      (mAbs). By114 is a valuable marker for detecting the emergence of a PNH clone
      before the Ham's test becomes positive and is a more sensitive detector of
      deficient GPI-anchored proteins than other mAbs.

PMID- 8542936
TI  - Effects of CD34+ selection and T cell immunodepletion on cord blood hematopoietic
      progenitors: relevance to stem cell transplantation.
AB  - Cord blood (CB) has been used recently for stem cell transplantation. We have
      investigated two different approaches to deplete CB samples of T cells capable of
      mounting graft-vs.-host disease (GVHD). The methods used were selection of CD34+
      cells using avidin-biotin columns (CellPro) and T cell immunodepletion with T10B9
      monoclonal antibody (mAb) plus complement. Using the avidin-biotin columns, 10.3%
      of the original CD34+ cells were recovered. Although this technique yielded a
      population containing 60 +/- 5.5% CD34+ cells, about 1 log of CFU-GM progenitors
      were lost. In contrast, after the T10B9 mAb and complement immunodepletion, 75 +/
      19% and 62 +/- 7% of the CD34+ cells and CFU-GM were recovered, respectively. T
      cell depletion was 3.6 logs using the CellPro columns and 2.2 logs after
      immunodepletion. To investigate whether cell losses following T cell depletion
      could be overcome by ex vivo expansion, cells were cultured in the presence of
      recombinant human interleukin-3 (rhIL-3) and recombinant human c-kit ligand (stem
      cell factor [rhSCF]) for 7 days. There were 14- and six-fold expansions in the
      number of progenitors recovered after CellPro and immunodepletion, respectively.
      To asses the engraftment potential of expanded cells, we used a murine
      transplantation model in which the presence of human cells was identified by the
      anti-CD45 mAb. Cells expanded in vitro engrafted in irradiated BNXid mice as
      efficiently as nonexpanded cells, suggesting that expansion did not affect their
      transplantability. This study shows that both techniques resulted in significant
      T cell depletion of CB. Furthermore, in vitro expansion could overcome cell
      losses sustained during the separation techniques without impairing the
      engraftment potential of the expanded cells.

PMID- 8542937
TI  - Serum levels of endogenous and exogenous granulocyte colony-stimulating factor
      after autologous blood stem cell transplantation.
AB  - Although the administration of recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) enhances myeloid engraftment and reduces infectious morbidity
      after autologous and allogeneic bone marrow transplantations, the effect of rhG
      CSF on neutrophil recovery in autologous blood stem cell transplantation (ABSCT)
      is controversial. We previously demonstrated that a low dose, delivered
      subcutaneously, of rhG-CSF (50 micrograms/m2) accelerates neutrophil recovery in
      ABSCT, but the optimal dosage of rhG-CSF is not known. To elucidate the effect of
      rhG-CSF on neutrophil recovery, we determined serum levels of endogenous and
      exogenously administered G-CSF in 24 patients receiving ABSCT. Of these, five
      received bolus subcutaneous injection of 50 micrograms/m2 rhG-CSF, 10 received
      150 micrograms/m2, and nine received no rhG-CSF. Endogenous G-CSF levels rose
      immediately after ABSCT, and an inverse correlation was found between the serum
      level of G-CSF and the absolute neutrophil count (r = -0.73, p < 0.01). The pre
      dose level in patients receiving rhG-CSF rose gradually, reaching a maximum
      between days 3 and 6. The level gradually decreased as the neutrophil count began
      to rise, even through administration of the same dose of rhG-CSF continued.
      Pharmacokinetic data showed that the half-life of elimination of G-CSF (t1/2)
      exceeded 15 hours during severe neutropenia but decreased during the recovery of
      neutrophils. These observations suggest that neutrophils provide a negative
      feedback mechanism for clearing G-CSF from the circulation. Pre-dose levels of G
      CSF in patients receiving 50 micrograms/m2 rhG-CSF reached 10 ng/mL, equivalent
      to the concentrations used in clonogenic assay in vitro to stimulate myeloid
      progenitor cells.

PMID- 8542938
TI  - Hematopoietic growth factors after HLA-identical allogeneic bone marrow
      transplantation in patients treated with methotrexate-containing graft-vs.-host
      disease prophylaxis.
AB  - The use of hematopoietic growth factors (HGFs) in the allogeneic transplant
      setting has sometimes been avoided for fear of stimulating leukemic cell growth
      and intensifying graft-vs.-host disease (GVHD). However, neither an increase in
      relapse rate nor an aggravation of GVHD has been routinely described when HGFs
      are used after allogeneic bone marrow transplantation (allo-BMT). Early outcomes
      after HLA-matched allo-BMT in 26 patients with hematologic malignancies treated
      with recombinant human granulocyte colony-stimulating factor (rhG-CSF) or
      recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      from the day of transplantation were analyzed. Results were compared to those
      from a series of 38 patients treated earlier with an identical approach, but not
      scheduled to receive HGFs after transplantation. All patients received a
      preparative regimen consisting of etoposide, cyclophosphamide, and total-body
      irradiation and GVHD prophylaxis with cyclosporine and a short course of
      methotrexate (MTX). The analysis has shown that the duration of neutropenia was
      significantly decreased in the group of patients treated routinely with HGFs
      (median 17 vs. 20 days; p < 0.001). These patients also required fewer days of
      intravenous antibiotic therapy (median 20 vs. 34 days; p < 0.001), had fewer
      positive blood and tissue cultures (median 2 vs. 12 and 13 vs. 28; p = 0.02 and p
      = 0.05, respectively), needed fewer packed red blood cell transfusions (median 7
      vs. 11; p < 0.03), and were discharged earlier from the hospital (median 33.5 vs.
      39 days; p < 0.001). The use of HGFs was not associated with an increase in acute
      GVHD or early leukemic relapse. No side effects were attributable to the
      simultaneous administration of MTX and HGF during the neutropenic period. A trend
      toward better 100-day actuarial survival for patients treated with rhG-CSF or
      rhGM-CSF did not reach statistical significance. A decrease in the number of
      early deaths from fungal or bacterial infections was found in the cytokine
      treated group (p = 0.05). These data suggest that the early use of rhG-CSF or
      rhGM-CSF after HLA-matched allo-BMT in hematologic malignancies accelerates
      engraftment, reduces hospitalization time, and improves outcome, without
      increasing acute GVHD or early relapse. Because MTX-based prophylaxis regimens
      are associated with prolonged neutropenia, the routine use of HGFs after
      transplantation may be particularly useful in regimens including MTX.

PMID- 8542939
TI  - 5-Fluorouracil-resistant CD34+ cell population from peripheral blood of CML
      patients contains BCR-ABL-negative progenitor cells.
AB  - Despite the marked expansion of leukemic cells observed in the hematopoietic
      system of chronic myeloid leukemia (CML) patients, there is clinical and
      experimental evidence that normal nonclonal cells persist in the bone marrow (BM)
      and peripheral blood (PB) of patients in the early chronic phase. In this study,
      we attempt to select the benign progenitor-enriched population from the PB of CML
      patients. The CD34+ cells isolated from the PB of 12 CML patients in the chronic
      phase were treated with low doses (5 or 10 micrograms/mL) of 5-fluorouracil (5
      FU). We expanded these cells for 7 days in liquid cytokine-mediated cultures.
      This expansion in the presence of interleukin-1 (IL-1) plus stem cell factor
      (SCF) plus IL-3 or leukemia inhibitory factor (LIF) plus SCF plus IL-3 seemed at
      least to preserve the initial clonogenic potential of CD34+ and 5-FU-resistant
      CD34+ cells. For the presence of BCR-ABL, mRNA from each of the 12 patients was
      studied by reverse-transcriptase-polymerase chain reaction (RT-PCR) on 10-15
      pooled CFU-GM colonies plucked from methylcellulose cultures of starting and
      expanded populations. Although all PCR results were positive for colonies
      harvested before liquid culture, we were able to identify BCR-ABL-negative
      colonies from an expanded CD34+ population cultured in the presence of
      recombinant cytokines in 11 of 12 patients studied. 5-FU pretreatment of CML
      CD34+ cells markedly reduced their clonogenic potential and growth factor
      mediated cell proliferation but favored higher frequency of BCR-ABL-free
      colonies. In conclusion, these data show that 5-FU-resistant CD34+ cells from the
      PB of CML patients contain normal progenitor cells, which can be selected and
      expanded in short-term cytokine-mediated cultures.

PMID- 8542940
TI  - Characterization of c-kit expression by primitive hematopoietic progenitors in
      umbilical cord blood.
AB  - Human umbilical cord blood (CB) appears to be an exciting new source of
      transplantable stem cells for a variety of clinical conditions. In this study, we
      have attempted to further characterize the primitive progenitors in CB. First we
      analyzed the effects of early-acting growth factors on blast cell colony
      formation from CD34+ progenitors. Addition of Steel factor (SF), interleukin-6
      (IL-6), or granulocyte colony-stimulating factor (G-CSF) to cultures containing
      interleukin-3 enhanced blast cell colony formation. These results indicated that
      cell cycle-dormant progenitors are present in CB. Next, based on results obtained
      in the murine system, we tested whether c-kit expression could separate the CB
      progenitors into cycle-dormant vs. cycle-active progenitors. Cells were separated
      into CD34+ c-kit-, c-kitlow, and c-kithigh. The results suggested that the c
      kitlow population contains the majority of cycle-dormant progenitors and the c
      kithigh population contains most of the forming cells were in the c-kitlow
      population, while the opposite is true for other colony-forming cells. Expression
      of c-kit may be useful in identifying CB progenitors with long-term engraftment
      capability.

PMID- 8542941
TI  - Proliferative response of human marrow myeloid progenitor cells to in vivo
      treatment with granulocyte colony-stimulating factor alone and in combination
      with interleukin-3 after autologous bone marrow transplantation.
AB  - We have recently reported that the hematologic recovery of patients with non
      Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) undergoing autologous bone
      marrow transplantation (BMT) is significantly faster when recombinant human
      interleukin-3 (rhIL-3) is combined with recombinant human granulocyte colony
      stimulating factor (rhG-CSF) in comparison with patients receiving G-CSF alone.
      In this paper, we studied the kinetic response and concentration of BM progenitor
      cells of 17 patients with lymphoid malignancies submitted to autologous BMT and
      treated with the G-CSF/IL-3 combination. The results were compared with those of
      five lymphoma patients receiving the same pretransplant conditioning regimen
      followed by G-CSF alone. rhG-CSF was administered as a single subcutaneous (sc)
      injection at the dose of 5 micrograms/kg/d from day 1 after reinfusion of
      autologous stem cells; rhIL-3 was added from day 6 at the dose of 10
      micrograms/kg/d sc (overlapping schedule). In both groups (G-CSF- and G-CSF/IL-3
      treated patients), cytokine administration was discontinued when the absolute
      neutrophil count (ANC) was >0.5 x 10(9)/L of peripheral blood (PB) for 3
      consecutive days. After treatment with the CSF combination, the percentage of
      marrow colony-forming units-granulocyte/macrophage (CFU-GM) and erythroid
      progenitors (BFU-E) in S phase of the cell cycle increased from 9.3 +/- 2% to
      33.3 +/- 12% and from 14.6 +/- 3% to 35 +/- 6%, respectively (p < 0.05).
      Similarly, we observed an increased number of actively cycling megakaryocyte
      progenitors (CFU-MK and BFU-MK). Conversely, G-CSF augmented the proliferative
      rate of CFU-GM (22.6 +/- 0.6% compared to a baseline value of 11.5 +/- 3%; p <
      0.05) but not of BFU-E, CFU-MK, or BFU-MK, and the increase of S-phase CFU-GM was
      significantly lower than that observed in the posttreatment samples of patients
      receiving IL-3 in addition to G-CSF. The frequency of hematopoietic precursors in
      the BM, expressed as the number of colonies formed per number of cells plated,
      was unchanged or slightly decreased in both groups of patients. Because of the
      increase in marrow cellularity, however, a significant augmentation of the
      absolute number of both CFU-GM (3605 +/- 712/mL BM vs. 2213 +/- 580/mL; p < 0.05)
      and BFU-E (4373 +/- 608/mL vs. 3027 +/- 516/mL; p < 0.05) was reported after
      treatment with G-CSF/IL-3 but not G-CSF alone. Similarly, administration of the
      cytokine combination resulted in a higher number of CD34+ cells/mL BM, and their
      concentration was significantly greater than that observed in the posttreatment
      samples of G-CSF patients. Finally, we investigated the responsiveness to CSFs,
      in vitro, of highly enriched CD34+ cells, collected after priming with G-CSF in
      vivo (i.e., after 5 days of G-CSF administration). Our results demonstrated that
      pretreatment with G-CSF modified the response of BM cells to subsequent
      stimulation with additional CSFs. The results presented in this paper indicate
      that in vivo administration of two cytokines increases the proliferative rate and
      concentration of BM progenitor cells to a greater degree than G-CSF alone. These
      results support the role of growth factor combinations for accelerating
      hematopoietic recovery after high-dose chemotherapy.

PMID- 8542942
TI  - Increasing the yield of harvested bone marrow cells by raising room temperature
      during marrow collection.
AB  - The time it takes to harvest bone marrow before transplantation could be reduced
      significantly by increasing the temperature of the operating room by 8-10 degrees
      C, to about 28-30 degrees C. In healthy donors, the collected volume of marrow
      was increased from 22.45 to 36.31 mL/min; in patients who received chemotherapy
      previously, from 21.67 to 29.98 mL/min. The time to collect a volume of 1200 mL
      marrow could be reduced significantly, from 57.78 to 38.25 minutes in healthy
      donors and from 71.07 to 43.36 minutes in patients who received chemotherapy
      previously, without any loss of quality of the sampled marrow. Operation time and
      thereby time of anesthesia could be reduced significantly by heating the
      operating room to a temperature of 28-30 degrees C. Harvesting at higher room
      temperature did not result in any adverse side effects for the patients. The
      procedure to increase the body temperature could be simplified by using electric
      blankets and aluminum foils for wrapping to avoid heat emission.

PMID- 8542943
TI  - VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity
      following autologous or allogeneic bone marrow transplantation.
AB  - Graft-vs.-leukemia (GVL) is postulated to be the principal mechanism responsible
      for continued remission after allogeneic bone marrow transplantation (BMT). The
      specific cytotoxic effectors mediating this effect are as yet undefined, but the
      major histocompatibility complex (MHC)-nonrestricted lysis of tumor cell lines by
      natural killer (NK) and lymphokine-activated killer (LAK) cells from recipients
      of allogeneic BMTs has been proposed as an in vitro correlate of GVL. In vitro
      culture or treatment in vivo with interleukin-2 (IL-2) is associated with
      enhanced NK cytotoxicity and lysis of NK-resistant targets (LAK cytotoxicity).
      NK, LAK, and cytotoxic T lymphocytes (CTL) have cytotoxic properties against
      autologous and allogeneic leukemic targets. These immune effector cells require
      receptor-ligand interaction for target recognition and adhesion via specific
      molecules such as integrins, a group of heterodimeric transmembrane
      glycoproteins. The integrins include the very late activation (VLA) subfamily,
      which all share the same beta 1 subunit but have distinct chains. VLA-6 (CDw49f)
      has been identified on NK cells and binds to laminin, a basement membrane protein
      found on malignant tumor cells but not normal cells. Monoclonal antibodies (mAbs)
      to laminin have been found to inhibit in vitro cytotoxicity of the tumor cell
      line K562, suggesting an important role for VLA-6 in this interaction. The
      specific aim of this study was to investigate the role of VLA-6 in the
      interactions of the tumor cell lines K562 and Daudi with peripheral blood
      lymphocytes (PBL) acting as effectors in cell-mediated cytotoxicity from normal
      volunteers, patients recovering from chemotherapy, and patients recovering from
      autologous or allogeneic BMT. In over 96% of assays, incubation of effector cells
      with anti-CDw49f mAbs led to detectable inhibition of NK and LAK cell-mediated
      cytotoxicity. More notably, the degree of anti-VLA6-induced suppression of LAK
      activity was significantly greater in the normal donors than in any of the
      patient groups, despite a significantly lower incidence of expression of VLA-6 on
      NK cells from controls than from patients. This implies a reduced role for this
      adhesion molecule in LAK activity following some form of in vivo stimulation.
      This hypothesis is supported by the observation that addition of exogenous IL-2
      to the cultures ameliorated the effect of VLA-6 blockade, although the incidence
      and level of VLA-6 expression was unchanged by IL-2. In contrast, VLA-6 blocking
      led to a greater reduction in NK activity of BMT recipients than of normal
      donors, demonstrating that the VLA-6 adhesion pathway is important in this group
      of patients. These results indicate that the VLA-6-laminin interaction is
      important in normal NK-target interaction but may play a less significant role in
      the innate cytotoxic response post-BMT, perhaps reflecting subtle differences in
      the subsets of NK cells present in BMT recipients compared with normal donors.

PMID- 8542944
TI  - Differential expression of L-selectin, VLA-4, and LFA-1 on CD34+ progenitor cells
      from bone marrow and peripheral blood during G-CSF-enhanced recovery.
AB  - To examine mechanisms of mobilization and homing of hematopoietic progenitor
      cells, coexpression of CD34 and the adhesion molecules L-selectin (CD62L), VLA-4
      (alpha 4 beta 1-integrin, CD49d/CD29), and LFA-1 (alpha L beta 2-integrin,
      CD11a/CD18) was evaluated. Samples from leukapheresis (LP) products and bone
      marrow (BM) were obtained on the same day from patients who received granulocyte
      colony-stimulating factor (G-CSF) after cytotoxic chemotherapy. The proportion of
      CD34+ cells expressing L-selectin tended to be greater in LP products compared
      with BM. In samples from both sources, the mean fluorescence intensity of CD34
      was significantly greater on CD34+/L-selectin-positive cells compared with the
      CD34+/L-selectin-negative cell subset. Three-color immunofluorescence showed that
      early CD34+/HLA-DRdim or CD34+/HLA-DR- progenitor cells were strongly positive
      for L-selectin, whereas L-selectin-negative cells were only found in the CD34+HLA
      DRbright subset. The mean fluoresence intensity of VLA-4 and LFA-1 was
      significantly greater on CD34+ cells from BM compared with LP products. Moreover,
      a distinct population of CD34dim/VLA-4bright and CD34dim/LFA-1bright cells was
      found only in samples from BM. This subset may be enriched for myeloid progenitor
      cells, since the cloning efficiency of CD34+ cells for CFU-GM was significantly
      greater in BM samples than in LP products. Binding of CD34+ cells to endothelial
      cells was partially inhibited by a blocking antibody to beta 2-integrin. In
      conclusion, L-selectin is expressed in significant amounts on more primitive
      CD34+ cells which circulate in considerable numbers in the peripheral blood. This
      suggests that L-selectin plays a role in redistribution and homing of
      hematopoietic progenitor cells to the bone marrow following cytotoxic damage.
      Conversely, strong expression of VLA-4 and LFA-1 was mainly found on lineage
      committed progenitor cells of the bone marrow.

PMID- 8542945
TI  - Time course of interferon-gamma production deficiency after autologous and
      allogeneic stem cell transplantation for malignancies.
AB  - While success of autologous bone marrow transplantation (BMT) for malignancies
      largely depends on the cytotoxicity of the ablative regimen, achievement of
      relapse-free survival after allogeneic BMT is thought to be enhanced by
      immunologic effects. We therefore investigated in vivo and in vitro production of
      interferon-gamma (IFN-gamma), soluble interleukin-2 (IL-2) receptor alpha-chain
      (sCD25), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) in patients before and during various time
      periods up to 2 years after autologous and allogeneic BMT. Cytokine levels were
      assessed in patient plasma and in supernatants of patient-derived peripheral
      blood mononuclear cells (PBMNC) cultured for 3 days in the presence of T cell
      specific stimulation via CD3 plus IL-2. Our studies show that IFN-gamma plasma
      levels are decreased in autologous graft recipients before and during the first
      30 days posttransplant. In allogeneic graft recipients, IFN-gamma plasma levels
      are also decreased during the first 30 days posttransplant, but otherwise are
      comparable to normal control (NC) values. In vitro stimulated PBMNC from
      autologous graft recipients also exhibit an IFN-gamma production defect before
      and during the first 30 days posttransplant. In contrast, before and up to 30
      days after allogeneic BMT, stimulated IFN-gamma production is comparable to NC
      values but then gradually decreases, reaching its trough levels at between 61 and
      180 days post-BMT. The IFN-gamma production defects in both patient groups seem
      to be specific, as sCD25, TNF-alpha, and GM-CSF production in stimulated PBMNC is
      normal or even enhanced at any time after autologous or allogeneic BMT. Deficient
      IFN-gamma production in patient-derived PBMNC does not correlate with variation
      in monocyte, T cell, or natural killer (NK) cell numbers during the
      posttransplantation course.

PMID- 8542946
TI  - Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation
      with donor peripheral blood lymphocytes.
AB  - Allogeneic bone marrow transplantation (BMT) is the treatment of choice for
      hematologic malignancies resistant to conventional chemotherapy and for patients
      who are at high risk for relapse. Until recently, no cure could be offered to
      patients relapsing following allogeneic BMT. We present our long-term
      observations of the first patient with remission reinduced by allogeneic cell
      therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we
      review the cumulative international experience with allo-CT used to treat 163
      patients, 105 with CML and 58 with other hematologic diseases, who relapsed
      following allogeneic BMT. The first patient treated by allo-CT was diagnosed with
      acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic
      and extramedullary relapse shortly after BMT. He was given infusions of donor
      (sister) PBL in multiple increments. Subsequently, he developed mild, reversible
      graft-vs-host disease (GVHD) in parallel with regression of all hematologic and
      cytogenetic disease manifestations. More than 8 years after allo-CT, he is
      disease-free with Karnofsky score 100% and no evidence of residual male cells by
      PCR. International data show that relapse after BMT was successfully reversed by
      donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic
      myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic
      diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell
      depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients
      with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete
      response after allo-CT was obtained in recipients of both TCD-BMT and unmodified
      BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100
      (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha
      interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of
      patients with other diseases. The cumulative experience shows that allo-CT can
      successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and
      even more effectively of chronic leukemia independently of alpha-interferon
      therapy. Although GVHD was frequent among responders, accompanied occasionally by
      transient or irreversible marrow aplasia, remissions were also obtained in
      patients with no GVHD. Allo-CT should therefore be considered as treatment of
      choice for overt relapse or de novo minimal residual disease post-BMT.
      Administration of donor peripheral blood lymphocytes in graded increments at an
      early stage of relapse may be the best approach for combining optimal timing at
      the stage of minimal disease while controlling and minimizing the risk of GVHD on
      an individual basis.

PMID- 8542947
TI  - Myeloid lineage involvement in acute lymphoblastic leukemia: a morphology
      antibody chromosomes (MAC) study.
AB  - We looked for clonal chromosomal abnormalities in myeloid cell lineages in the
      bone marrow aspirates from six children with acute lymphoblastic leukemia (ALL).
      The study was carried out using a combination of MAC (morphology, antibody,
      chromosomes) and in situ hybridization procedures. In patients whose leukemic
      cells expressed only lymphoid antigens, we found chromosomal aberrations in CD10-
      and CD20/22-positive lymphoid cells. Mature CD22+ and CD3+ lymphocytes did not
      have the chromosomal aberrations. In one patient whose leukemic cells also
      expressed myeloid-associated antigens, the clonal chromosome aberrations were
      seen not only in the CD10+ and CD19+ blasts, but also in glycophorin A-positive
      morphologically nonleukemic erythroblasts.

PMID- 8542948
TI  - Long-term cultures to evaluate engraftment potential of CD34+ cells from
      peripheral blood after mobilization by chemotherapy with and without GM-CSF.
AB  - In this study we used a long-term culture system to evaluate engraftment
      potential of human peripheral blood (PB) cells mobilized by chemotherapy (CT)
      associated or not with granulocyte-macrophage colony-stimulating factor (GM-CSF).
      In six patients who underwent blood cell transplantation, PB CD34+ cells were
      cultured after mobilization and were compared to CD34+ cells in steady state from
      PB and bone marrow (BM). Qualitative differences were shown between PBC samples
      obtained after CT with and without GM-CSF. Despite similar CFU-GM counts at
      culture initiation, GM-CSF-mobilized CD34+ cells might contain a lower proportion
      of primitive stem cells, as suggested by the significant decrease in CFU-GM
      numbers produced beyond week 5 compared to CT-mobilized CD34+ cells (p = 0.033).
      Likewise, the percentage of CFU-GM produced beyond week 5 in relation to initial
      input was significantly lower than steady-state PB (p = 0.039) and than CT
      mobilized CD34+ cells (p = 0.033). However, this CFU-GM production with GM-CSF
      mobilized PB CD34+ cells was not different from cultures with BMC CD34+ cells.
      These results suggest that GM-CSF can mobilize CFU-GM in the blood mainly by
      differentiation at the expense of the primitive stem cell compartment. It appears
      valuable to define clearly for each mobilizing procedure a particular threshold
      of CFU-GM which reflects sufficient numbers of primitive stem cells to ensure
      long-term engraftment.

PMID- 8542949
TI  - The inhibition of lymphokine-activated killer cells in acute myeloblastic
      leukemia is mediated by transforming growth factor-beta 1.
AB  - In acute myeloblastic leukemia (AML), the T cell response and cytotoxic activity
      are impaired at time of diagnosis due to not-yet-identified soluble
      immunosuppressing factors. The inhibition of autologous antileukemic immune
      response by these factors may support immunosurveillance of AML. A well-known
      inhibitor of lymphokine-activated killer (LAK) cell activity is transforming
      growth factor-beta 1 (TGF-beta 1). To evaluate the possible significance of TGF
      beta 1 for the impaired cytotoxic activity in AML at time of diagnosis, we looked
      for the TGF-beta 1-specific mRNA, for the production and release of TGF-beta 1,
      and for its relevance for immunosuppressing activities in AML. In the culture
      supernatants of 18 investigated AMLs, we detected various amounts of TGF-beta
      protein. The TGF-beta 1 and TGF-beta 2 protein concentrations were 105 pg/mL (<
      50-240 pg/mL) and 32 pg/mL (< 2-91 pg/mL), respectively. In 13 of 15 patients,
      the leukemic blasts expressed TGF-beta 1 mRNA. To exclude possible interferences
      with contaminating mononuclear cells (MNC), the data were confirmed by analysis
      of sorted blast cells and leukemic cell lines. All investigated leukemic cell
      lines expressed TGF-beta 1 protein and mRNA. The culture supernatants of AMLs
      inhibited LAK activity strongly in a dose-dependent manner. The inhibition of
      cytotoxicity could be restored by the addition of neutralizing TGF-beta 1
      antibodies. The data suggest TGF-beta 1 to be a relevant factor for the
      inhibition of cytotoxic activities in AMLs.

PMID- 8542950
TI  - A mononuclear cell dose of 3 x 10(8)/kg predicts early multilineage recovery in
      patients with malignant lymphoma treated with carmustine, etoposide, Ara-C and
      melphalan (BEAM) and peripheral blood progenitor cell transplantation.
AB  - We have assessed the potential use of the mononuclear cell (MNC) content as the
      sole assessment of graft quality in 35 patients receiving BEAM (carmustine,
      etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous
      peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma.
      PBPCs were mobilized with cyclophosphamide and granulocyte colony-stimulating
      factor (G-CSF), and each patient underwent two (n = 20) or three (n = 15)
      apheresis procedures. Median cell yields were 5.08 x 10(8) MNC/kg (range 1.59
      15.70 x 10(8)) and 73.10 x 10(4) CFU-GM/kg (range 0.09-346.72 x 10(4)). All
      patients achieved hematologic recovery. Median days to neutrophils > or = 0.1 x
      10(9)/L, neutrophils > or = 0.5 x 10(9)/L, and platelets > or = 25 x 10(9)/L were
      11 (range 8-15), 13 (range 10-37), and 11 (range 7-41), respectively. A close
      correlation was observed between the MNC and CFU-GM dose (r = 0.79, p < 0.0001).
      We have previously defined a minimum threshold CFU-GM dose of 20 x 10(4)/kg for
      patients undergoing high-dose therapy. This corresponds with an MNC dose of 3 x
      10(8)/kg. Comparison of engraftment in patients receiving 3 x 10(8) MNC/kg with
      those receiving lower doses demonstrated significantly longer times to recovery
      of neutrophils to > or = 0.5 x 10(9)/L and platelets to > or = 25 x 10(9)/L. All
      patients receiving an MNC dose of > or = 3 x 10(8)/kg achieved neutrophil and
      platelet recovery by days 12 and 24, respectively. These preliminary data
      demonstrate that for patients with lymphoma undergoing PBPC mobilization
      according to this protocol and treatment with BEAM chemotherapy, assessment of
      MNC dose alone is sufficient to predict early hematologic recovery. Additional
      assays such as CFU-GM or CD34+ cell counts may not be necessary if this MNC dose
      is reinfused.

PMID- 8542951
TI  - Analysis of cord blood CD34+ cells purified after cryopreservation.
AB  - Many practical issues regarding processing blood samples for cord blood banking
      remain. After cryopreservation, a reduction in clonogenicity has been reported,
      although it is unknown whether this is associated with lower potential for long
      term engraftment. CD34+ cell purification of cryopreserved cord blood (CB) may be
      important for the clinical application of in vitro expansion. We compared purity,
      yield, clonogenicity, and growth in long-term stromal-based culture of fresh and
      cryopreserved CD34+ purified cells (n = 12) using the miniMACS separation system.
      Mean purity of CD34+ cells was 93% when processed before and 73% when processed
      after cryopreservation. Fresh CD34+ cells had higher clonogenic potential than
      cryopreserved cells (45 vs 20%, p < 0.05) in CFU-Mix assays, indicating that
      progenitor cell loss during cryopreservation is due in part to reduced cloning
      efficiency of viable CD34+ cells. In long-term culture (LTC) on irradiated normal
      human bone marrow stroma (n = 7), CFU-GM production in the two groups was the
      same over 12 weeks, suggesting identical long-term culture-initiating cell (LTC
      IC) numbers. We conclude that apparent clonogenic cell loss during
      cryopreservation is associated with relative sparing of the more primitive LTC
      ICs. CFU-Mix assays may therefore underestimate the transplant potential of
      cryopreserved CB. Purification of CD34+ cells following cryopreservation gives
      sufficient purity for detailed evaluation of CD34+ cells and for stem cell
      expansion.

PMID- 8542952
TI  - Characterization of acute bone marrow graft rejection in T cell-depleted,
      partially mismatched related donor bone marrow transplantation.
AB  - The purpose of this study was to characterize the phenotype and clonality of the
      T cell population in patients who experience acute rejection (AR) following bone
      marrow transplantation (BMT) from a partially mismatched related donor (PMRD).
      Phenotypic analysis was performed using flow cytometry, assignment of donor/host
      lineage by cytogenetics or HLA-specific flow cytometry, and analysis of the T
      cell receptor (TCR) by reverse-transcriptase polymerase chain reaction (RT-PCR).
      We have previously reported the initial appearance in the blood of AR patients of
      host CD8+brightCD3low T cells that progressively express increasing amounts of
      CD3+ cells. We now report that this cell population can differentiate into either
      a cytotoxic T cell phenotype (CD3+CD8+HLA-DR+CD57-) usually associated with AR of
      grafts from matched unrelated donors or a suppressor T cell phenotype
      (CD3+CD8+CD57+HLA-DR-) usually associated with AR of grafts from matched sibling
      donors. Analysis of the TCR V beta subsets from two patients revealed sorted host
      CD3+CD8+ cells (purity 90-95%) from the first patient to express V beta 18 almost
      exclusively. In a second patient with late rejection (55 days post-BMT), the
      CD3+CD8+ cells were predominantly restricted to V beta 1, 5.1, 7, 9, and 18.
      Although CD3+CD8+ T cells are known to be associated with AR, cytotoxic and
      suppressor lineages in AR from the same type of BMT and clonal distribution of T
      cells in AR have not been reported. Preliminary results suggest that V beta
      expression in AR of PMRD grafts is restricted and host T cell phenotype may vary.
      Further studies will investigate whether specific mismatches correlate with
      specific V beta usage and/or host T cell phenotype.

PMID- 8542953
TI  - A highly sensitive polymerase chain reaction method reveals the ubiquitous
      presence of maternal cells in human umbilical cord blood.
AB  - Umbilical cord blood is considered an alternate source of hematopoietic stem
      cells in bone marrow transplantation. However, its use might be hampered by
      contamination of neonatal blood with maternal cells, which could contribute
      unacceptably to graft-vs.-host disease (GVHD) after transplant. In a previous
      study (Socie et al., Blood 83:340, 1994), we used polymerase chain reaction (PCR)
      amplification of minisatellite sequences (sensitivity 1-0.1%) to address the
      question of this contamination. In a single case among 47 analyzed, we were able
      to detect a maternal-specific allele in the cord blood sample. We have now
      studied the same cord samples using a highly sensitive, allele-specific PCR
      amplification method. A maternal allele could be discriminated from neonate
      alleles in 10 cases and maternal cells were detected in all 10 cord blood
      samples. These cells amounted to 10(-4) to 10(-5) of cord blood nucleated cells.
      In three cases, cord blood separated cell subpopulations could be analyzed and
      were found to contain maternal cells at about the same level. The presence of
      maternal cells at such a low level in cord blood samples probably would have no
      effect on GVHD in a clinical setting of transplantation but raises interesting
      questions in terms of materno-fetal immune tolerance and transmission of viruses
      (in particular human immunodeficiency virus) from infected mother to child.

PMID- 8542954
TI  - Inhibition of chronic myelogenous leukemia cells harboring a BCR-ABL B3A2
      junction by antisense oligonucleotides targeted at the B2A2 junction.
AB  - Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder
      characterized by the BCR-ABL hybrid gene. Two types of hybrid BCR-ABL mRNA have
      been found, B2A2 and B3A2. As the BCR-ABL rearrangement is specific to leukemic
      cells, selective inhibition of leukemic cell growth by BCR-ABL antisense
      oligonucleotides (ASO) has been reported in vitro for CML patients and cell
      lines. However, controversial results have been obtained from preclinical studies
      using anti-BCR-ABL ASO, as nonspecific inhibition of leukemic cell growth was
      evidenced in some cases. B3 exon secondary structure was deduced from its
      sequence and found to be a loop. According to this predictive structure of exon
      B3, a 56-mer antisense oligonucleotide targeting the polypurine bases from the
      B2A2 junction was devised which would inhibit proliferation (MTT assay) of B3A2
      junction cell lines (K562 and a murine cell line Ba/F3 transfected with the B3A2
      junctional sequence). This ASO had a hairpin-like secondary structure and was
      found to be much more resistant to the action of nucleases than control 18-mer
      standard oligonucleotides. Hybridization to its target mRNA occurs via formation
      of a triplex structure. A concentration of 5 microM of specific 56-mer B2A2 ASO
      was necessary to demonstrate 50% optical density (OD) reduction for K562 cell
      line and Ba/F3 transformed by B3A2 cDNA. Sense and non-sense 56-mer sequence or
      18-mer linear ASO showed no effect for these concentrations. Western blot showed
      a partial inhibition of P210 protein; expression of P145abl remains unchanged.
      The 56-mer ASO also inhibited the proliferation of B2A2 junction cell line BV173
      at the same concentration and showed no effect on the HL60 cell line used as
      control.

PMID- 8542955
TI  - Purging of peripheral blood stem cells yields BCR-ABL-negative autografts in
      patients with BCR-ABL-positive acute lymphoblastic leukemia.
AB  - Remission marrow from patients with BCR-ABL+ acute lymphoblastic leukemia (ALL)
      achieving clinical remission (CR) after induction or consolidation chemotherapy
      according to the German multicenter adult ALL (GMALL) protocol showed high titers
      of residual BCR-ABL+ cells. Therefore, we initiated a pilot study to monitor
      circulating BCR-ABL+ cells and to collect, purge, and autograft peripheral blood
      stem cells (PBSC) in these patients. After GMALL 05/93 high-risk phase II of
      induction chemotherapy (high-dose AraC 3 g/m2 x 8 does and mitoxantrone 10 mg/m2
      x 3 doses), patients received 5-10 micrograms/kg subcutaneous recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) daily. Mobilized CD34+ cells
      peaked between 20 and 26 days after starting chemotherapy at 4.8-75.6 (median
      10.8) x 10(4)/mL peripheral blood (PB) (n = 5). Patients treated with additional
      chemotherapy cycles failed to mobilize adequate numbers of CD34+ cells. PB stem
      cells (PBSC) were purged using a cocktail of CD10, CD19, and AB4 monoclonal
      antibodies (mAbs) coupled to immunomagnetic beads (IMB). The median recoveries of
      total nucleated cells (TNC) and CD34+ cells after mAb/IMB purging were 84 and
      81%. The peak numbers of CD34+ cells collected in a single leukapheresis were
      median 8.6 x 10(6)/kg pre- and 5.2 x 10(6)/kg postpurge (n = 4). The absolute
      prepurge CD19+ cells were as low as median 2.7 (range 1.4-19) x 10(6) per
      leukapheresis. Residual BCR-ABL+ cells in unpurged leukapheresis products were
      assessed by limiting-log10-dilution nested reverse-transcriptase polymerase chain
      reaction (RT-PCR) as one in 10(5) to one in 10(6) normal cells and were
      consistently undetectable in all purged PBSC autografts. We conclude that
      sufficient numbers of CD34+ cells for PBSCT can be collected after phase II but
      not at later stages of the GMALL 05/93 high risk protocol; PBSC grafts are 3 log
      less contaminated with residual BCR-ABL+ cells compared to an historical series
      of 13 autologous BM grafts; and purging of PBSC with mAb/IMB is feasible with
      minor loss of CD34+ cells and abolished BCR-ABL signals in the grafts.

PMID- 8542956
TI  - Optimizing the CD34+ and CD34+Thy-1+ stem cell content of peripheral blood
      collections.
AB  - We have previously described a sensitive and specific CD34 enumeration assay and
      report here a prospective analysis of 25 myeloma patients undergoing PBSC
      mobilization using this assay to determine the optimal days for collection of
      CD34+ and CD34+Thy-1+ cells after chemotherapy and growth factor mobilization.
      Correlations between frequency of peripheral blood CD34+ cells, circulating white
      blood cell (WBC) count, apheresis CD34+ cell count, nucleated cell count (NCC),
      and numbers of apheresis colony-forming units granulocyte/macrophage (CFU-GM)
      were determined. To assess levels of the more primitive subsets of CD34+ cells in
      the PBSC collections, coexpression of the Thy-1 antigen (CDw90) on CD34+ cells
      was also assessed. Marked heterogeneity was noted between patients with apheresis
      samples containing a median NCC of 4.2 x 10(8)/kg (range 1.3-8.1), median CFU-GM
      17 x 10(4)/kg (range 0.15-32 x 10(4)/kg), and median CD34+ cell count of 1.39 x
      10(6)/kg (range 0.02-6.6). The frequency of CD34+ cells in PBSC collections
      coexpressing Thy-1 was also heterogenous (6.2-50% of CD34+ cells), median 21.6%,
      mean 24.7 +/- 2%. The apheresis CD34+ cell count correlated with the peripheral
      blood CD34+ cell percentage (r = 0.71, p < 0.0001) but only weakly with the
      peripheral WBC. Apheresis CD34+Thy-1+ cell numbers correlated strongly with the
      circulating CD34+ cell numbers (r = 0.80), but no correlation was noted between
      these candidate stem cells and the peripheral WBC. In contrast, apheresis CFU-GM
      levels correlated most strongly with the peripheral WBC count (r = 0.61, p <
      0.0001). The apheresis CD34+ cell count correlated with apheresis CFU-GM (r =
      0.75, p < 0.0001) but not with the apheresis NCC. Apheresis CD34+Thy-1+ counts
      significantly correlated only with the apheresis CD34+ cell count and not with
      the apheresis CFU-GM or NCC. A higher percentage of circulating and apheresis
      CD34+ cells expressing Thy-1 were found on day 1 of collection, and the
      percentage of CD34+ cells expressing Thy-1 decreased on each subsequent day of
      measurement: median of 22% day 1 vs. 16.6% day 4, p = 0.04. This study therefore
      confirms that accurate quantitation of circulating CD34+ cells best predicts the
      optimal day for apheresis collection of CD34+ and CD34+Thy-1+ cells and is
      superior to the WBC count in this regard. Furthermore, the candidate stem cell
      (CD34+Thy-1+) subset is most prevalent during the earliest phases of CD34+ cell
      mobilization.

PMID- 8542957
TI  - Efficient retroviral mediated transfer of the glucocerebrosidase gene in CD34+
      enriched umbilical cord blood human hematopoietic progenitors.
AB  - Obtaining efficient transfer of a normal gene and its sustained expression in
      self-renewing hematopoietic stem cell populations is a central concern for gene
      therapy initiatives. Potentially, 10(8) to 10(9) CD34+ enriched cells per patient
      will be required for transduction and subsequent reimplantation. These studies
      present an efficient method for the transduction of human CD34+ cells that can be
      used in a clinical study of gene transfer. The method uses a centrifugation
      enhanced technique for the retroviral-mediated transfer of the normal human
      glucocerebrosidase (GC) gene to human CD34+ enriched umbilical cord blood cells
      (CB). Previous studies had described high expression of GC in CD34+ enriched
      cells but had not reported transduction efficiency in the progenitor population
      specifically. The data demonstrate an average transduction efficiency in the
      progenitor cell population of 50% as measured by polymerase chain reaction (PCR)
      for the integrated GC-cDNA in clonogenic cells. Measurements of enzyme activity
      comparing transduced and nontransduced fractions at 6 days posttransduction
      indicate an average enzyme increase of six-fold over normal background levels.
      PCR of colony forming units-granulocyte/macrophage (CFU-GM) plated at 6 weeks
      from long-term culture-initiating cell (LTC-IC) cultures also indicates transfer
      of the transgene to early progenitor cells. Finally, experiments were carried out
      with the human erythroleukemia cell line, TF-1, to estimate the durable
      expression of the transgene. Enzymatic activities in transduced TF-1 cultures
      remained at 30-fold above the activity of nontransduced controls. The expression
      persisted for 6 weeks in culture. These studies demonstrate efficient
      transduction of early progenitor cells and sustained expression of the transgene
      in cell cultures.

PMID- 8542958
TI  - Cytokine mobilization of peripheral blood stem cells in patients with Gaucher
      disease with a view to gene therapy.
AB  - As clinical trials for gene therapy in Gaucher disease (GD) begin, questions
      regarding the biology of the hematopoietic stem cell in this disease remain
      unanswered. This study demonstrates the ability to mobilize and collect CD34+
      cells in three patients with the disorder. Our RAC/FDA-approved clinical trial
      utilizes mobilized peripheral blood stem cells (PBSC) as the target cells for
      gene transfer. In this approach, a white blood cell fraction is collected by
      apheresis, enriched for CD34+ cells, and transduced with a retroviral vector
      carrying the glucocerebrosidase (GC) gene. Transduced cells from the patient with
      activity corrected to at least normal levels will be returned to the patient
      without myelosuppressive therapy. We report here the effect of cytokines in
      mobilizing PBSC in three patients with GD. Two (patients 1 and 2) were given
      granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg/d and
      one (patient 3) was given 10 micrograms/kg/d for 10 days. Leukaphereses were done
      daily for 5 days and the products enriched for CD34+ cells using the clinical
      Ceprate (CellPro) column. The CD34+ cells in all fractions were monitored daily
      during mobilization and leukaphereses. Subset analysis for the expression of Thy
      1, CD38, HLA-DR, and CD33 on the CD34+ cells was performed. An increase in CD34+
      cells in the peripheral blood was noted from day 5 onward (up to a six-fold
      increase). Up to a 625-fold enrichment in CD34+ cells in the apheresis product
      was noted using the clinical Ceprate column. Totals of 1.2, 3.5, and 2.1 x 10(6)
      CD34+ cells/kg were collected in the three patients. A diminution in the percent
      of CD34+/Thy-1+ cells was noted with enrichment. In vitro retroviral transduction
      of the CD34-enriched cells using centrifugation promoted transduction protocol
      previously described (Bahnson AB et al., Centrifugal enhancement of retroviral
      mediated gene transfer. Journal of Virology Methods 54:131, 1995) and modified
      for clinical use, demonstrated a mean transduction efficiency of 37% (range 8.3
      87.1%) in clonogenic cells and up to 50% in long-term culture-initiating cells
      (LTC-IC) at week 6. Significantly, we have been able to achieve up to a 50-fold
      increase in the level of GC above deficient levels in the patients' CD34+
      enriched cells when maintained in vitro in culture. The study demonstrates that
      up to a six-fold increase in CD34+ cells in the PB can be achieved with cytokines
      in patients with GD. CD34+ cells can be collected in numbers sufficient for
      conventional transplantation and transduced efficiently in vitro. In gene therapy
      trials for genetic disorders to date, myelosuppressive therapy is not advocated.
      The clinical trial will demonstrate whether this number of transduced CD34+ cells
      will be adequate for competitive engraftment of genetically corrected PBSC.

PMID- 8542959
TI  - Increased apoptosis in aplastic anemia bone marrow progenitor cells: possible
      pathophysiologic significance.
AB  - We have quantitated apoptotic cells by flow cytometry in human bone marrow (BM)
      and peripheral blood (PB) from normal donors and aplastic anemia (AA) patients,
      using the fluorescent DNA-binding dye 7-amino actinomycin D (7AAD). No
      significant difference was found in baseline percent apoptosis between normal and
      AA samples. Serum deprivation induced cell death to a greater degree in AA
      samples than in normal samples, but this was not significant. Using dual staining
      with anti CD34 antibody and 7AAD, we have shown that CD34+ progenitors in normal
      PB are significantly more apoptotic than those in normal BM. AA BM CD34+ cells
      contain a significantly greater proportion of apoptotic cells than normal BM
      CD34+ cells. Those AA patients with the lowest absolute number of CD34+ cells
      showed the highest proportion of apoptotic CD34+ cells. This appears to be
      related to clinical severity (transfusion dependence) at the time of study. We
      conclude that apoptosis is accelerated in AA BM progenitors and that this may
      contribute to the stem cell deficiency characteristic of this disorder.

PMID- 8542960
TI  - Detection of bcr-abl mRNA in single progenitor colonies from patients with
      chronic myeloid leukemia by PCR: comparison with cytogenetics and PCR from
      uncultured cells.
AB  - Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia
      (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl
      expression in fresh blood and/or bone marrow, and bcr-abl expression in single
      hematopoietic progenitor colonies generated from blood and/or bone marrow.
      Expression of bcr-abl was proven by a reverse "nested primer" polymerase chain
      reaction (PCR) that is able to detect 1 pg of hybrid mRNA. We performed 108
      investigations on 68 patients containing all three parameters: 12 on untreated
      patients, seven after interferon-alpha (IFN-alpha), seven after low-dose cytosine
      arabinoside (Ara-C), 22 after cyclic high-dose hydroxyurea (HU), 49 after
      allogeneic BMT, five before and three after stem cell mobilization, and three
      after autologous stem cell transplantation (ASCT). In 53 cases (49%),
      cytogenetics and PCR gave identical results. In 40 cases (37%), PCR from single
      colonies gave additional information compared to cytogenetics (e.g., mosaic in
      colonies when all metaphases were positive or negative). Most interesting were
      the results of one patient after IFN, one patient after ASCT, and 10 patients
      after BMT (14 investigations = 13%), showing only Ph'-negative mitoses
      accompanied by a negative nested primer PCR from fresh blood/bone marrow but
      single bcr-abl-positive progenitor colonies. False-positive results could be
      widely excluded by repeated insertion of negative controls into the experiments.
      One explanation for these results could be that CML, progenitors survive in the
      patient's body by being inactive and not proliferating. These cells express no or
      very little RNA and bcr-abl is not detectable by reverse PCR. When stimulated ex
      vivo in a colony assay by external growth factors, cells proliferate and produce
      detectable amounts of hybrid mRNA. The value of these observations is not clear.
      A follow-up of the patients will show if such sleeping progenitors can be
      activated in vivo. Concluding our observations, we can say that in special cases
      (therapy follow-up, detection of minimal residual disease) it could be useful to
      perform a PCR analysis of single progenitors in parallel with the routine
      investigations.

PMID- 8542961
TI  - The identification of MHC identical siblings without HLA typing.
AB  - By comparing genomic sequences of different MHC haplotypes, we defined highly
      polymorphic markers. After amplification, electrophoresis, and scanning with a
      laser, we have identified profiles that serve as signatures of the haplotype and
      its component alleles. One set of markers can be used to define the block that
      includes HLA-B and HLA-C, among other loci. Another set provides signatures for
      the entire HLA-DR and -DQ multigene cluster. By profile overlay, it is possible
      to identify siblings who share both haplotypes from HLA-C to HLA-DQ. Here we
      demonstrate the value of genomic analysis ("block matching") in selecting
      genotypically identical siblings prior to transplantation. Forty-six siblings
      from 10 families were genotyped by family analysis after meticulous HLA, C4, and
      Bf typing including molecular methods for HLA-DRB1. In 43 siblings, the haplotype
      assignments were unequivocal. Twenty-two identical sibling pairs could then be
      compared with 77 nonidentical pairs. Independent genomic analysis yielded
      entirely concordant results. In three siblings, the possibility of parental
      recombination was considered but could not be defined by the conventional typing.
      By genomic analysis, however, it was clear that recombination had indeed occurred
      in one case. In the remaining two cases, additional, more telomeric markers will
      be necessary to resolve the issue. This simple, cost-effective method has
      immediate application to the identification of matched pairs (HLA-C to HLA-DQ)
      for bone marrow and renal transplantation.

PMID- 8542962
TI  - Alterations in both the hematopoietic microenvironment and the progenitor cell
      population follow the recovery from myeloablative therapy and bone marrow
      transplantation.
AB  - Experimental data are conflicting, but suggest that after recovery from bone
      marrow transplantation (BMT), alterations in clonogenic growth and myeloid
      microenvironment remain. To further characterize this abnormality, light-density
      marrow cells from 15 patients who were in remission from hematologic malignancies
      and had undergone BMT (eight allogeneic and seven autologous) were studied in two
      culture systems after their marrows had reconstituted and were compared to
      normal. The preconditioning regimen for transplantation was fractionated total
      body irradiation (TBI) 12 Gy, cyclophosphamide 120 mg/kg, and total nodal
      irradiation 6 Gy. Bone marrow mononuclear cells (MNCs) from the patients and
      controls were divided in two fractions; stromal layers (SL) were prepared from
      the first fraction. To examine the attributes of the stroma, the petri dish
      surface covered by the SL was measured after 5 weeks in culture, and
      representative layers were trypsinized and stained with Sudan black, butirate
      esterase, and acid and alkaline phosphatases. Stromal layers were also studied
      for their support in the development of blastic colonies (CFU-BI). From the
      second fraction, the CD34+ population was selected with immunomagnetic beads, and
      1 x 10(4) progenitors from patients or controls were seeded onto the opposite
      group of preformed stroma. Stroma-adhesive precursors were scored for the
      formation of CFU-BI (> 20 cells) on day 5 of culture. Nonadherent selected CD34+
      cells were recovered by standardized washing and quantitated in clonogenic assays
      (CFU-GM). The median patient age was 26 (SD 6.65) years, and eight of 15 patients
      were female. The median infused bone marrow (BM) MNC number was 0.9 x 10(8)/kg
      (SD 0.31). Grafts were studied at a median of 37 (SD 48.43) months from
      transplant. SL from the patients failed to reach confluence by 5 weeks (median
      dish area covered 55.5% [SD 32.38] vs. control: 100% [SD 2.35]; p = 0.0001). BMT
      CD34+ progenitors gave 19.5 (SD 42.2) CFU-Bl, significantly lower than those from
      normal individuals (127 [SD 62.2]; p = 0.01) when panned on control stroma, while
      control CD34+ cells were poorly supported on BMT layers (corrected for surface,
      median 2.5 [SD 42.2] CFU-Bl; p = 0.039). Although numbers of stroma nonadherent
      CFU-GM were not different between the groups (median BMT 56 [SD 54.5] vs. control
      62.5 [SD 60.76]; p > 0.05), the ratio of CFU-Bl to CFU-GM showed a significant
      reduction in adherent CD34+ progenitors in BMT patients (median 0.28 [SD 0.44]
      vs. normal 2.09 [SD 1.3]; p = 0.04). None of the values were significantly
      different between patients receiving allogeneic or autologous grafts. We conclude
      that post-BMT stroma is defective and supports CFU-Bl growth poorly. Moreover, we
      documented a significant reduction within the CD34+ cells in the adherent
      primitive clonogenic precursors that was compensated by a proportional increase
      in the more mature CFU-GM.

PMID- 8542963
TI  - The putative role of HLA-C recognition in graft versus host disease (GVHD) and
      graft rejection after unrelated bone marrow transplantation (BMT).
AB  - We assessed cytotoxic activity of large granular lymphocytes (LGLs) derived from
      10 patients transplanted from molecular HLA-C mismatched (5) and matched (5)
      unrelated donors and compared it to the cytotoxic activity of 10 patients
      transplanted from HLA-identical siblings. In addition, we correlated clinical
      outcome with the level of molecular HLA-C disparity in a cohort of 22 patients
      who underwent unrelated BMT. Cells obtained from patients transplanted (related
      or unrelated) from fully matched donors did not generate allospecific lysis of
      patient (pre-BMT) or donor PHA blasts. Five of nine patients who received BMT
      from HLA-C mismatched unrelated donors developed > grade II graft-vs.-host
      disease (GVHD), and four developed graft rejection. Cells derived from three of
      three patients with GVHD lysed patients' pre-BMT PHA blasts. In the patients with
      GVHD grade III-IV, cytotoxicity was higher (60-70%) than in the patient with
      grade II GVHD (20%) (p < 0.05). Cytotoxic cells derived from one patient who
      rejected his graft lysed donor PHA blasts. In one remaining patient who had graft
      rejection followed by autologous rescue, no in vitro allospecificity was
      observed. In summary, cytotoxic cells from patients transplanted with marrow
      mismatched at locus C demonstrated in vitro cytolysis of PHA blasts, and this
      phenomenon showed positive correlation with the clinical outcome of the BMT.
      These findings may indicate specific allorecognition. A mismatch at locus C
      leading to alloreactivity should be considered a risk factor in determining an
      appropriate match for allogeneic BMT, especially when the donor is unrelated.

PMID- 8542964
TI  - Natural killer cell numbers and activity in mobilized peripheral blood stem cell
      grafts: conditions for in vitro expansion.
AB  - Peripheral blood stem cells (PBSC) are increasingly being used as an alternative
      to autologous bone marrow (BM) for hematologic rescue after high-dose
      chemoradiotherapy in the treatment of hematologic and nonhematologic
      malignancies. Mobilization procedures such as chemotherapy and/or hematopoietic
      growth factor administration are employed to allow for the graft enrichment in
      hematopoietic stem cells and progenitors and to accelerate trilineage recovery
      after transplant. The influence of these mobilization procedures on the lymphoid
      populations in the graft and on immunologic recovery after transplant remains to
      be determined. We studied six consecutive patients undergoing PBSC high-volume
      collections after cyclophosphamide (Cyc) and granulocyte colony-stimulating
      factor (G-CSF) administration and observed that NK cell numbers (phenotypically
      defined as CD3-CD56+ by flow cytometry) and activity (evaluated by a 51Cr release
      assay) fully recovered after 4-5 weeks; high numbers of functionally active NK
      cells (42.1-212.1 x 10(6)/kg b.w.) were present in the grafts, and their
      percentage and cytotoxic activity rose from the beginning to the end of the
      harvesting procedure in most cases. CD3-CD56+ and CD34+ cell numbers peaked at
      the same time point during harvesting, which differed from one patient to
      another. T (CD3+) cells were always present during harvest, and CD4 and CD8
      numbers showed interdonor variability. When we cultured leukapheresed PBSC in the
      presence of interleukin-2 (IL-2) (10-1000 U/mL) for 6-8 days, we were able to
      expand the NK population three- to 5.4-fold; 100 U/mL appears to be the best
      concentration to generate high numbers of cytotoxic NK cells. Pilot studies also
      suggest that this short exposure to IL-2 does not affect the CD34+ cells. We
      conclude that PBSC grafts mobilized by combined Cyc and G-CSF and harvested
      through high-volume leukapheresis contain high numbers of cytotoxic NK cells that
      can be expanded in vitro by exposure to IL-2. In the setting of PBSC transplant,
      ex vivo immunomodulation aimed at increasing the NK cell numbers and activity is
      feasible and may prove to be useful in inducing a graft-vs.-tumor effect, thereby
      decreasing the relapse rate after transplant.

PMID- 8542965
TI  - Astroglial responses in photochemically induced focal ischemia of the rat cortex.
AB  - This study investigated astroglial responses after focal cerebral ischemia in the
      rat cortex induced by photothrombosis. Astrocyte activation was studied at
      various time points by immunocytochemistry for glial fibrillary acidic protein
      (GFAP) and vimentin (VIM). We found a dual astrocytic response to focal ischemia:
      In the border zone of the infarct, GFAP-positive astrocytes were present within 2
      days and persisted for 10 weeks. These astrocytes additionally expressed VIM.
      Remote from the ischemic lesion, cortical astrocytes of the entire ipsilateral
      hemisphere transiently expressed GFAP, but not VIM, beginning on day 3 after
      photothrombosis. This response had disappeared on day 14. By recording DC
      potentials, five to seven spreading depressions (SD) could be detected on the
      cortical surface during the first 2 h after photothrombosis. Treatment with
      MK801, a non-competitive NMDA-receptor antagonist, completely abolished SD and
      remote ipsilateral astrocytic activation, while the reaction in the border zone
      of the infarct remained unchanged. Functionally, persistent astrocytosis around
      the infarct might be induced by leukocyte-derived cytokines, while NMDA-receptor
      mediated SD might cause remote responses.

PMID- 8542966
TI  - Cooperative effects of neuronal ensembles.
AB  - Electrophysiological properties of neurons as the basic cellular elements of the
      central nervous system and their synaptic connections are well characterized down
      to a molecular level. However, the behavior of complex noisy networks formed by
      these constituents usually cannot simply be derived from the knowledge of its
      microscopic parameters. As a consequence, cooperative phenomena based on the
      interaction of neurons were postulated. This is a report on a study of global
      network spike activity as a function of synaptic interaction. We performed
      experiments in dissociated cultured hippocampal neurons and, for comparison,
      simulations of a mathematical model closely related to electrophysiology. Numeric
      analyses revealed that at a critical level of synaptic connectivity the firing
      behavior undergoes a phase transition. This cooperative effect depends crucially
      on the interaction of numerous cells and cannot be attributed to the spike
      threshold of individual neurons. In the experiment a drastic increase in the
      firing level was observed upon increase of synaptic efficacy by lowering of the
      extracellular magnesium concentration, which is compatible with our theoretical
      predictions. This "on-off" phenomenon demonstrates that even in small neuronal
      ensembles collective behavior can emerge which is not explained by the
      characteristics of single neurons.

PMID- 8542967
TI  - The vestibulo-ocular reflex of the squirrel monkey during eccentric rotation and
      roll tilt.
AB  - The vestibulo-ocular reflexes (VOR) are determined not only by angular
      acceleration, but also by the presence of gravity and linear acceleration. This
      phenomenon was studied by measuring three-dimensional nystagmic eye movements,
      with implanted search coils, in six male squirrel monkeys during eccentric
      rotation. Monkeys were rotated in the dark at a constant velocity of 200
      degrees/s (centrally or 79 cm off axis) with the axis of rotation always aligned
      with gravity and the spinal axis of the upright monkeys. The monkey's orientation
      (facing-motion or back-to-motion) had a dramatic influence on the VOR. These
      experiments show that: (a) the axis of eye rotation always shifted toward
      alignment with gravito-inertial force; (b) the peak value of horizontal slow
      phase eye velocity was greater with the monkey facing-motion than with back-to
      motion; and (c) the time constant of horizontal eye movement decay was smaller
      with the monkey facing-motion than with back-to-motion. All of these findings
      were statistically significant and consistent across monkeys. In another set of
      tests, the same monkeys were rapidly tilted about their naso-occipital (roll)
      axis. Tilted orientations of 45 degrees and 90 degrees were maintained for 1 min.
      Other than a compensatory angular VOR during the angular rotation, no consistent
      eye velocity response was observed during or following the tilt for any of the
      six monkeys. The absence of any eye movement response following tilt weighs
      against the possibility that translational linear VOR responses are due to simple
      high-pass filtering of the otolith signals. The VOR response during eccentric
      rotation was divided into the more familiar angular VOR and linear VOR
      components. The angular component is known to depend upon semicircular canal
      dynamics and central influences. The linear component of the response decays
      rapidly with a mean duration of only 6.6 s, while the axis of eye rotation
      rapidly aligns (< 10 s) with gravito-inertial force. These results are consistent
      with the hypothesis that the measurement of gravito-inertial force by the otolith
      organs is resolved into central estimates of linear acceleration and gravity,
      such that the central estimate of gravitational force minus the central estimate
      of linear acceleration approximately equals the otolith measurement of gravito
      inertial force.

PMID- 8542968
TI  - Modeling the vestibulo-ocular reflex of the squirrel monkey during eccentric
      rotation and roll tilt.
AB  - Model simulations of the squirrel monkey vestibulo-ocular reflex (VOR) are
      presented for two motion paradigms: constant velocity eccentric rotation and roll
      tilt about a naso-occipital axis. The model represents the implementation of
      three hypotheses: the "internal model" hypothesis, the "gravito-inertial force
      (GIF) resolution" hypothesis, and the "compensatory VOR" hypothesis. The internal
      model hypothesis is based on the idea that the nervous system knows the dynamics
      of the sensory systems and implements this knowledge as an internal dynamic
      model. The GIF resolution hypothesis is based on the idea that the nervous system
      knows that gravity minus linear acceleration equals GIF and implements this
      knowledge by resolving the otolith measurement of GIF into central estimates of
      gravity and linear acceleration, such that the central estimate of gravity minus
      the central estimate of acceleration equals the otolith measurement of GIF. The
      compensatory VOR hypothesis is based on the idea that the VOR compensates for the
      central estimates of angular velocity and linear velocity, which sum in a near
      linear manner. During constant velocity eccentric rotation, the model correctly
      predicts that: (1) the peak horizontal response is greater while "facing-motion"
      than with "back-to-motion"; (2) the axis of eye rotation shifts toward alignment
      with GIF; and (3) a continuous vertical response, slow phase downward, exists
      prior to deceleration. The model also correctly predicts that a torsional
      response during the roll rotation is the only velocity response observed during
      roll rotations about a naso-occipital axis. The success of this model in
      predicting the observed experimental responses suggests that the model captures
      the essence of the complex sensory interactions engendered by eccentric rotation
      and roll tilt.

PMID- 8542969
TI  - Control of locomotion in marine mollusc Clione limacina. X. Effects of
      acetylcholine antagonists.
AB  - The swimming central pattern generator (CPG) of the pteropod mollusc Clione
      limacina is located in the pedal ganglia. It consists of three groups of
      interneurons (7, 8, and 12) which generate the rhythmical activity and determine
      the temporal pattern of the motor output, that is, phasic relations between
      different groups of motor neurons supplying dorsal (group 1 and 3 motor neurons)
      and ventral (group 2 and 4 motor neurons) muscles of the wings. In this work
      peripheral and central effects of acetylcholine (ACh) antagonists on the swimming
      control in C. limacina has been studied. The ACh antagonist atropine blocked
      transmission from the wing nerves to wing muscles, while gallamine triethiodide
      (Flaxedil), d-tubocurarine, and alpha-bungarotoxin did not affect the
      neuromuscular transmission. In the pedal ganglia, the ACh antagonists atropine
      and gallamine triethiodide blocked inhibitory postsynaptic potentials (IPSPs)
      produced by group 8 interneurons onto group 7 interneurons and motor neurons of
      groups 1 and 3. d-Tubocurarine and alpha-bungarotoxin did not affect IPSPs
      produced by group 8 interneurons. Although atropine and gallamine triethiodide
      blocked IPSPs produced by group 8 interneurons in antagonistic neurons, these
      drugs did not influence excitatory postsynaptic potentials (EPSPs) produced by
      group 8 interneurons onto group 12 interneurons. The main pattern of the swimming
      rhythm with an alternation of two phases of the swimming cycle persisted after
      elimination of inhibitory connections from group 8 interneurons to antagonistic
      neurons by the ACh antagonists. This suggests that there are redundant mechanisms
      in the system controlling C. limacina's swimming. This redundancy ensures
      reliable operation of the system and contributes to its flexibility.

PMID- 8542970
TI  - Synaptic depression in visual cortex tissue slices: an in vitro model for
      cortical neuron adaptation.
AB  - Synaptic depression was assessed from intracellular recordings in cortical tissue
      slices. Evoked postsynaptic potentials exhibited synaptic depression with an
      exponential or double exponential decrease (time constants: < 1-30 s) in
      amplitude during repetitive afferent stimulation by short trains of
      suprathreshold stimuli. Depressed synaptic responses with an exponential time
      course (time constants: 10 s-8 min) during presentation of similar short trains
      of stimuli every 5 or 10 s. Cortical cells recorded extracellularly in cat visual
      cortex show similar time constants of response decrement during adaptation to
      moving stripes. Postsynaptic voltage- or ion-regulated conductances and chloride
      conductances do not appear to be involved in synaptic depression. Input
      resistance changes and effects of injection of chloride indicate a lack of GABAA
      receptor-mediated effects. Hyperpolarizing or depolarizing neurons, and pairing
      polarization with afferent stimulation, also did not affect synaptic depression.
      This distinguishes these processes from long-term depression and long-term
      potentiation. Our results suggest that the most likely mechanisms of synaptic
      depression and adaptation in cortical cells are presynaptic decrease in
      transmitter release and/or receptor desensitization. Short-term postsynaptic
      changes may also occur after synaptic depression.

PMID- 8542971
TI  - The development of goal-directed reaching in infants: hand trajectory formation
      and joint torque control.
AB  - Nine young infants were followed longitudinally from 4 to 15 months of age. We
      recorded early spontaneous movements and reaching movements to a stationary
      target. Time-position data of the hand (endpoint), shoulder, and elbow were
      collected using an optoelectronic measurement system (ELITE). We analyzed the
      endpoint kinematics and the intersegmental dynamics of the shoulder and elbow
      joint to investigate how changes in proximal torque control determined the
      development of hand trajectory formation. Two developmental phases of hand
      trajectory formation were identified: a first phase of rapid improvements between
      16 and 24 weeks of age, the time of reaching onset for all infants. During that
      time period the number of movement units per reach and movement time decreased
      dramatically. In a second phase (28-64 weeks), a period of "fine-tuning" of the
      sensorimotor system, we saw slower, more gradual changes in the endpoint
      kinematics. The analysis of the underlying intersegmental joint torques revealed
      the following results: first, the range of muscular and motion-dependent torques
      (relative to body weight) did not change significantly with age. That is, early
      reaching was not confined by limitations in producing task-adequate levels of
      muscular torque. Second, improvements in the endpoint kinematics were not
      accomplished by minimizing amplitude of muscle and reactive torques. Third, the
      relative timing of muscular and motion-dependent torque peaks showed a systematic
      development toward an adult timing profile with increasing age. In conclusion,
      the development toward invariant characteristics of the hand trajectory is
      mirrored by concurrent changes in the control of joint forces. The acquisition of
      stable patterns of intersegmental coordination is not achieved by simply
      regulating force amplitude, but more so by modulating the correct timing of joint
      force production and by the system's use of reactive forces. Our findings support
      the view that development of reaching is a process of unsupervised learning with
      no external or innate teacher prescribing the desired kinematics or kinetics of
      the movement.

PMID- 8542972
TI  - Luminance neurons in the pretectal olivary nucleus mediate the pupillary light
      reflex in the rhesus monkey.
AB  - In humans and other primates, an increase in luminance in either eye elicits
      bilateral pupilloconstriction that is essentially equal in both eyes. Current
      models of the neural substrate for this clinically important light reflex propose
      that a retinorecipient pretectal nucleus projects bilaterally to the Edinger
      Westphal nucleus (EW), which contains the parasympathetic, preganglionic neurons
      controlling pupilloconstriction. Based on single-unit recording studies in
      anesthetized cats and rats, it has been further suggested that luminance neurons
      in only one pretectal nucleus, the pretectal olivary nucleus, mediate this
      reflex. However, to our knowledge, there have been no comparable
      electrophysiological studies in primates of the pupillary light reflex or the
      pretectal luminance neurons that mediate this reflex. To address this issue,
      single-unit recording and electrical microstimulation studies were carried out in
      the pretectum of alert, trained, rhesus monkeys. These studies demonstrated that
      the primate pretectum contains luminance neurons with the characteristics
      appropriate for mediating the pupillary light reflex and that these neurons are
      located in one retinorecipient pretectal nucleus, the pretectal olivary nucleus.
      Electrical microstimulation at the site of these neurons often elicited
      pupilloconstriction. Our results provide clear evidence for the involvement of
      the pretectum, and more specifically the pretectal olivary nucleus, in mediating
      the pupillary light reflex in primates.

PMID- 8542973
TI  - Reprogramming of muscle activation patterns at the wrist in compensation for
      elbow reaction torques during planar two-joint arm movements.
AB  - The relationship between wrist kinematics, dynamics and the pattern of muscle
      activation were examined during a two-joint planar movement in which the two
      joints moved in opposite directions, i.e. elbow flexion/wrist extension and elbow
      extension/wrist flexion. Elbow movements (ranging from 10 to 70 deg) and wrist
      movements (ranging from 10 to 50 deg) were performed during a visual, step
      tracking task in which subjects were required to attend to the initial and final
      angles at each joint. As the elbow amplitude increased, wrist movement duration
      increased and the wrist movement trajectories became quite variable. Analysis of
      the torques acting at the wrist joint showed that elbow movements produced
      reaction torques acting in the same direction as the intended wrist movement.
      Distinct patterns of muscle activation were observed at the wrist joint that were
      dependent on the relative magnitude of the elbow reaction torque in relation to
      the net wrist torque. When the magnitude of the elbow reaction torque was quite
      small, the wrist agonist was activated first. As the magnitude of the elbow
      reaction torque increased, activity in the wrist agonist decreased significantly.
      In conditions where the elbow reaction torque was much larger than the net wrist
      torque, the wrist muscle torque reversed direction to oppose the intended
      movement. This reversal of wrist muscle torque was directly associated with a
      change in the pattern of muscle activation where the wrist antagonist was
      activated prior to the wrist agonist. Our findings indicate that motion of the
      elbow joint is an important consideration in planning wrist movement.
      Specifically, the selection of muscle activation patterns at the wrist is
      dependent on the relative magnitude and direction of the elbow reaction torque in
      relation to the direction of wrist motion.

PMID- 8542974
TI  - A survey of spinal dorsal horn neurones encoding the spatial organization of
      withdrawal reflexes in the rat.
AB  - The withdrawal reflex pathways to hindlimb muscles have an elaborate spatial
      organization in the rat. In short, the distribution of sensitivity within the
      cutaneous receptive field of a single muscle has a spatial pattern that is a
      mirror image of the spatial pattern of the withdrawal of the skin surface ensuing
      on contraction in the respective muscle. In the present study, a search for
      neurones encoding the specific spatial input-output relationship of withdrawal
      reflexes to single muscles was made in the lumbosacral spinal cord in
      halothane/nitrous oxide-anaesthetized rats. The cutaneous receptive fields of 147
      dorsal horn neurones in the L4-5 segments receiving a nociceptive input and a
      convergent input from A and C fibres from the hindpaw were studied. The spatial
      pattern of the response amplitude within the receptive fields of 118 neurones was
      quantitatively compared with those of withdrawal reflexes to single muscles.
      Response patterns exhibiting a high similarity to those of withdrawal reflexes to
      single muscles were found in 27 neurones located in the deep dorsal horn. Twenty
      six of these belonged to class 2 (responding to tactile and nociceptive input)
      and one belonged to class 3 (responding only to nociceptive input). None of the
      neurones tested (n = 20) with reflex-like response patterns could be
      antidromically driven from the upper cervical cord, suggesting that they were
      spinal interneurones. With some overlap, putative interneurones of the withdrawal
      reflexes to the plantar flexors of the digits, the plantar flexors of the ankle,
      the pronators, the dorsiflexors of the ankle, and a flexor of the knee, were
      found in succession in a mediolateral direction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8542975
TI  - Direction-specific differences in the magnitude of abducens nerve responses
      during off-vertical axis rotation are a basic property of the utriculo-ocular
      reflex in frogs.
AB  - Abducens nerve multiunit responses were recorded in darkness from decerebrated
      frogs during steps of angular velocity about an axis tilted with respect to the
      earth vertical (off-vertical axis rotation, OVAR). Thereby, a rotating gravity
      vector activated utricular hair cells and modulated the abducens nerve discharge
      sinusoidally as a function of head position in space. As expected, a bias
      velocity response component and nystagmus-related changes in neural activity were
      absent, since frogs do not possess a functioning velocity storage mechanism.
      Responses increased as a function of the tilt angle and of the velocity and
      direction of the platform rotation. OVAR in the direction of the recorded
      abducens nerve (clockwise for the right and counterclockwise for the left
      abducens nerve) evoked significantly smaller responses than rotation in the
      opposite direction. The possible origin of these direction-specific response
      properties was further studied after lesioning various structures assumed to
      modify utriculo-ocular reflexes. Each of these lesions (ipsilateral
      hemilabyrinthectomy, cerebellectomy, contralateral canal nerve sections) had a
      specific effect on the recorded response properties, but none of them, nor
      combinations thereof, abolished the direction-specific characteristics of the
      responses as long as the contralateral utricular nerve branch remained intact.
      Our results demonstrate that direction-specificity is a property of the basic
      utriculo-ocular reflex that is independent of the velocity storage mechanism in
      the brainstem, of the intervestibular commissural system, of the inhibitory
      control by the cerebellum and of the central convergence of utricular and
      horizontal canal inputs. A simple, unidirectional interaction between central
      utricular neurons with adjacent functional polarization vectors is suggested as
      the basic element for the observed direction specificity.

PMID- 8542976
TI  - A kinematic and kinetic analysis of locomotion during voluntary gait modification
      in the cat.
AB  - As part of a study to characterize the postural reactions that occur during
      voluntary gait modification, we examined the kinematic, electromyographic (EMG),
      and kinetic responses that occurred when cats stepped over an obstacle placed in
      their path. Analyses of the kinematics as each of the forelimbs stepped over the
      obstacle showed that changes in joint angles were most pronounced at the elbow of
      the first (lead) limb, and at the shoulder of the second (trailing) limb. In the
      hindlimbs, there was a pronounced change in the knee joint angle in both the
      leading and trailing limbs. Examination of the horizontal and vertical velocities
      of the tip of the forepaw suggests that the movements can be divided into two
      phases: one in which the limb is rapidly lifted above and over the obstacle, and
      a slower one during which the limb is carefully repositioned on the floor. On the
      basis of the velocity profiles, we suggest that the repositioning of the paw on
      the support surface is more critically controlled for the forelimb than for the
      hindlimb. Analysis of the changes in the ground reaction forces in the supporting
      limbs during these gait modifications showed that there were two major increases
      in vertical reaction force. One of these occurred as the two forelimbs were
      straddling the obstacle, the other when the two hindlimbs were straddling it.
      There was also a net increase in the anteroposterior force that resulted in a
      small increase in propulsion as the cat stepped over the obstacle. Each change in
      the vertical ground reaction force was paralleled by a similar change in the
      amplitude of the EMG recorded from the respective extensor muscles. An analysis
      of the vertical displacement of the scapula and of the pelvis showed that there
      was a slight increase in the height of the scapula in the support limb just prior
      to and during the swing phase of the trailing forelimb, and a more pronounced and
      progressive change in the height of the pelvis prior to and during the passage of
      both hindlimbs over the obstacle. We suggest that the increases in vertical
      ground reaction force raise the height of the body sufficiently to allow,
      respectively, passage of the trail forelimb and each of the hindlimbs over the
      obstacle. The results are discussed with respect to both the biomechanical
      changes underlying these gait modifications and the neuronal mechanisms
      implicated in their control.

PMID- 8542977
TI  - Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem
      spinal cord preparations isolated from newborn rats.
AB  - In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst
      generating properties of preinspiratory (Pre-I) neurons in the rostral
      ventrolateral medulla, which have been suggested to be primary respiratory rhythm
      generating neurons, were studied by "perforated" whole-cell recordings using the
      antibiotic nystatin. Nystatin causes small pores to be formed in the cells,
      through which pass small monovalent ions. For blockade of chemical synaptic
      transmission, perfusate Ca2+ concentration was lowered to 0.2 mM and the Mg2+
      concentration was increased to 5 mM. In low-Ca2+, high-Mg2+ solution (referred to
      here as "low Ca"), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type),
      14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type
      neurons showed periodic depolarization of 5-12 mV in low Ca, at a rate of 12 +/-
      6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of
      the periodic depolarization and prolongation of the cycle period. Thus, the burst
      generations were voltage dependent. The firing frequency of tonic-type neurons
      was 2.3 +/- 1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons,
      the firing patterns changed to burst patterns during continuous
      hyperpolarization. Membrane depolarization by continuous outward current
      injection into some silent-type neurons (3 of 11 tested) induced bursting
      activity. Activity of C4 and Pre-I neurons was completely silent with 0.1-1
      microM tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type
      neurons (n = 3) were also silent with 1 microM TTX perfusion. Inspiratory neurons
      either became silent (n = 4) or fired tonically (n = 1) in low Ca. The present
      study by "perforated" whole-cell recordings confirmed that some Pre-I neurons
      possess intrinsic burst-generating properties, which were not attributable to
      phasic synaptic inputs.

PMID- 8542978
TI  - Fictive motor activities in adult chronic spinal rats transplanted with embryonic
      brainstem neurons.
AB  - The present study was designed to examine the effects of an intraspinal
      transplantation of embryonic brainstem neurons on fictive motor patterns which
      can develop in hindlimb nerves of adult chronic spinal rats. Seventeen adult rats
      were spinalized at T8-9 level and, 8 days later, a suspension of embryonic cells
      obtained either from the raphe region (RR, n = 8) or from the locus coeruleus
      (LC, n = 9) was injected caudally (T12-13) to the cord transection. Eight control
      animals (control rats) were spinalized and injected with vehicle under the same
      conditions. One to three months later, the animals were decorticated and fictive
      motor patterns were recorded in representative hindlimb nerves. The data revealed
      that both control and grafted spinal rats could exhibit two distinctly different
      fictive motor patterns, one which could be associated with stepping and the other
      with hindlimb paw shaking. They further showed that following transplantation of
      embryonic RR or LC neurons the excitability of the spinal stepping generator was
      increased, whereas that of the spinal neural circuits which generate hindlimb paw
      shaking was not significantly affected. A histological analysis performed on the
      spinal cord segments below the transection revealed complete absence of serotonin
      and noradrenaline immunoreactivity in control spinal animals and, in both types
      of grafted rats, an extensive monoaminergic reinnervation with synaptic contacts
      between monoaminergic transplanted neurons and host interneurons and/or
      motoneurons. The possible mechanisms by which grafted monoaminergic neurons can
      influence the spinal motor networks are discussed.

PMID- 8542979
TI  - Thermal images of somatic sensory cortex obtained through the skull of rat and
      gerbil.
AB  - Infrared images of the skull surface were obtained in urethane-anesthetized rats
      and gerbils before, during and after mechanical stimulation of the face and
      mystacial vibrissae on one side. Areas of increased temperature on the skull,
      localized mainly over the face area of the primary somatosensory cortex
      contralateral to the side of stimulation, appeared within 4-5 s after the onset
      of stimulation. Rarely, such temperature change was recorded bilaterally.
      Temperatures did not remain high on the intact skull in rats, but fell to
      baseline within minutes after stimulus onset regardless of stimulus duration. In
      rats in which the skull had been thinned and in gerbils with intact skull,
      temperatures remained elevated during the course of stimulation. We were unable
      to resolve the activation of individual vibrissae.

PMID- 8542980
TI  - Raphespinal and reticulospinal neurons project to the dorsal vagal complex in the
      rat.
AB  - Stimulation of the caudal raphe nuclei alters visceral functions. The caudal
      raphe nuclei project to the nucleus of the solitary tract, which receives the
      central terminations of vagal afferents and plays an important role in the
      central integration of autonomic activities. The caudal raphe nuclei also project
      to the somatic and preganglionic autonomic motoneurons of the spinal cord.
      Diamidino yellow was injected into the nucleus of the solitary tract, and fast
      blue was injected into either the cervical, thoracic, or lumbar spinal cord.
      Large numbers of double-labeled neurons were present within the caudal raphe
      nuclei and the adjacent reticular formation of the medial tegmental field. This
      observation documents that individual raphespinal and reticulospinal neurons
      project an axon collateral to the nucleus of the solitary tract. These data
      demonstrate the anatomic substrate for global modulation of the autonomic
      motoneuron pool by the caudal raphe nuclei.

PMID- 8542982
TI  - Immunohistochemical localization of a Shaker-related voltage-gated potassium
      channel protein in Schistosoma mansoni (Trematoda: Digenea).
AB  - We have recently isolated a cDNA (SKv1.1) encoding a Shaker-related K+ channel
      from the human parasitic trematode Schistosoma mansoni. In order to better
      understand the functions of SKv1.1 protein, the distribution of SKv1.1 protein in
      adult S. mansoni was analyzed by immunohistochemistry using a region-specific
      antibody. SKv1.1 proteins were widely expressed in the nervous and muscular
      systems. The strongest immunoreactivity (IR) was observed in the nervous system
      of both male and female. In the nervous system, IR for SKv1.1 proteins was
      localized in cell bodies and nerve fibers of the anterior ganglia, the central
      commissure, and the main nerve cords. IR was also observed in the dorsal and the
      ventral peripheral nerve nets, fine nerve fibers entering into a variety of
      structures such as the dorsal tubercles, longitudinal and ventral muscle fibers,
      and oral and ventral suckers. In the muscular system, SKv1.1 proteins were
      localized to the longitudinal, circular, and ventral muscle fibers of male as
      well as in isolated muscle fibers where native A-type K+ currents were measured.
      Moderate IR was also seen in a large number of cell bodies in the parenchyma.
      These results indicate that SKv1.1 protein may play an important role in the
      regulation of the excitability of neurons and muscle cells of S. mansoni.

PMID- 8542981
TI  - A behavioral model of excitotoxicity: retinal degeneration, loss of vision, and
      subsequent recovery after intraocular NMDA administration in adult rats.
AB  - To establish a new behavioral animal model of excitotoxicity, we injected adult
      rats intraocularly with a single dose of 2, 20, or 100 nmol of N-methyl-D
      aspartate (NMDA). We quantified visual impairment by plotting the size of the
      visual field in which the rats successfully oriented towards a small, moving
      target. In comparison to the saline-injected (contralateral) control side, the
      side injected with 2 nmol of NMDA was not significantly impaired. When injected
      with higher doses, the rats were nearly blind immediately after surgery, with
      only about 20% (20 nmol NMDA) or 10% (100 nmol NMDA) of residual vision. Within
      about 3 weeks, however, visual performance returned to near-normal levels.
      Simultaneous intraocular administration of a non-competitive NMDA-antagonist, MK
      801 (1 nmol), resulted in complete behavioral protection. NMDA administration led
      to a dose-dependent loss of cells within the ganglion cell layer, as assessed in
      whole-mounted retinae which were retrogradely labelled with horseradish
      peroxidase (HRP). Whereas 2 nmol of NMDA led to the loss of about 30% of retinal
      ganglion cells (RGCs), at higher NMDA doses only 13% of the RGCs survived. After
      the injection of 20 nmol of NMDA, large-diameter RGCs (> 22 microns) survived the
      lesion to a greater extent than small diameter cells (8-21 microns); at 100 nmol
      cells of all diameters were equally affected. The number of Nissl-stained cells
      with small diameters (< 11 microns), presumed to be displaced amacrine cells, was
      also affected by NMDA, although to a lesser degree. Analysis of behavioral
      performance (vision score) and the number of cells in the retina revealed a
      correlation of r = 0.76 between visual performance and the number of HRP-filled
      RGCs immediately after surgery. Lower correlations were found between visual
      performance and cells stained with Nissl of diameters smaller than 11 microns
      (presumed RGCs without retinofugal connections; r = 0.55 and r = 0.58,
      respectively). Because of the spontaneous recovery of vision, all correlations
      declined to values near 0 after 3 weeks. Thus, despite a dramatic loss of RGCs
      following NMDA administration, visual deficits recover significantly in adult
      rats within 2-3 weeks.

PMID- 8542983
TI  - Theileria sergenti and T. buffeli: polymerase chain reaction-based marker system
      for differentiating the parasite species from infected cattle blood and infected
      tick salivary gland.
AB  - Benign Theileria species in cattle. Theileria sergenti and T. buffeli, are
      morphologically indistinguishable. The polymerase chain reaction (PCR) was used
      to amplify the genes encoding the 33- and 34-kDa major piroplasm antigens
      (p33/34) of T. sergenti and T. buffeli from cattle blood infected with these
      parasites and tick salivary gland infected with T. sergenti. Following
      amplification, the p33 gene from T. sergenti and the p34 gene from T. buffeli
      were clearly differentiated using the restriction enzyme sites that were not
      shared between them. The oligonucleotide primer set, designed from the p33/34
      genes, was specific for these Theileria species, since no amplification was
      detected with DNA from Babesia ovata, B. bovis, Anaplasma marginale, A. centrale,
      Eperythrozoon wenyoni, bovine white blood cells, and uninfected tick salivary
      glands. One tenth vol of the template prepared from either 25 microliters of
      blood with 0.5% parasitemia or individual tick salivary glands with six infected
      acini allowed sufficient amplification for differentiation of the two parasite
      species by restriction enzyme digestion. In addition, this system could be used
      to demonstrate the simultaneous, experimentally induced infection of cattle with
      T. sergenti and T. buffeli. The PCR-based marker system therefore provides a
      means to differentiate T. sergenti from T. buffeli in infected cattle blood and
      infected tick salivary glands. This system may also be useful for the
      characterization of other benign Theileria species in cattle.

PMID- 8542984
TI  - Plasmodium: a quantitative molecular assay for detection of sporogonic-stage
      malaria parasites.
AB  - We present a molecular assay to detect malaria parasites during sporogonic
      development in the mosquito host. Specific primers for Plasmodium-specific small
      subunit ribosomal RNA sequences not present in mosquito RNA were used in a
      reverse transcriptase-polymerase chain reaction (RT-PCR) assay. A synthetic RNA
      quantitative competitor was made which included targets for two primers and a
      target sequence for a hybridization probe which is also present in the natural
      parasite ribosome. The heterobifunctional Tth polymerase was used to carry out
      both reverse transcription and DNA-dependent polymerase chain reaction in a
      single reaction tube. Ookinetes and sporozoites, the stages from the beginning
      and end of sporogonic development, respectively, were both recognized in the
      assay. The assay was calibrated for quantitation of sporozoites by making a
      standard curve with counted sporozoites. The linear range of the calibrated assay
      allowed accurate quantitation of parasite number over at least two orders of
      magnitude, from 10 to 1000 sporozoites, in each RT-PCR reaction.

PMID- 8542985
TI  - Onchocerca volvulus: identification and characterization of an immunogenic
      eggshell protein (Oveg1).
AB  - A major antigen recognized by human sera in Onchocerca volvulus infections is a
      parasite eggshell protein. The cDNA clone for this antigen was isolated from a
      lambda gt11 O. volvulus cDNA library using antisera from patients with high
      microfilarial counts. Sequence analysis of the cDNA clone predicts a
      polyglutamine repeat near the 5' end of the cDNA, and a motif of four arginines
      near the 3' end, reminiscent of that found in many regulatory proteins. The cDNA
      was subcloned into a yeast expression vector and reagent quantities of
      recombinant antigen produced in Saccharomyces cerevisiae. Antisera produced to
      the recombinant purified protein localized the antigen to the eggshell of
      developing microfilariae within the adult female uterus. No other sites of Oveg1
      expression were noted in adult worms, but labeling was seen in internal membrane
      structures of L3 larvae. Sera from infected chimps recognized Oveg1 only after
      infections became patent. Sera from infected humans showed reactivity to Oveg1
      that varied from 39 to 95%, depending upon the geographic location.

PMID- 8542986
TI  - Trypanosoma cruzi: a 52-kDa protein sharing sequence homology with glutathione S
      transferase is localized in parasite organelles morphologically resembling
      reservosomes.
AB  - We have previously isolated and characterized a Trypanosoma cruzi cDNA encoding a
      polypeptide with a molecular mass of 52 kDa (Tc52) sharing significant homology
      to glutathione S-transferase. In the present study, by molecular and
      immunological approaches, we showed that Tc52 is preferentially expressed by
      dividing forms of the parasite: (e.g., epimatigotes and amastigotes). Moreover,
      we could identify the reactive antigen in different T. cruzi strains. A different
      pattern of reactivity on immunoblots was observed in the case of Trypanosoma
      rangeli. Furthermore, immunofluorescence assays using T. cruzi epimastigote
      culture forms revealed that the reactive antigen is localized within cytoplasmic
      organelles morphologically ressembling the structures previously designated as
      the reservosome found mostly at the posterior end of the parasite. Furthermore,
      the antibodies did not react against trypomastigotes which emerged from infected
      fibroblasts, whereas amastigotes showed polar fluorescence. Immunogold labeling
      and electron micrographs further revealed that the Tc52 protein is mainly
      associated with organelles composed of a large network of multivesicular
      structures, the latter being more abundant in epimastigotes. Taken together,
      these results demonstrated that Tc52 is associated with organelles composed of a
      multivesicular network and appears to be developmentally regulated, being fully
      expressed by parasite dividing forms.

PMID- 8542987
TI  - Trypanosoma cruzi: parasite detection and strain discrimination in chronic
      chagasic patients from northeastern Brazil using PCR amplification of kinetoplast
      DNA and nonradioactive hybridization.
AB  - Blood samples from 172 individuals from northeastern Brazil were subjected to PCR
      amplification of Trypanosoma cruzi-specific kDNA sequences. This method enabled
      us to detect parasite DNA in 21 of 47 patients that were serologically positive.
      In addition, 1 patient that gave doubtful results with chagasic serology was
      confirmed as positive by PCR. We applied the same PCR detection method to the
      feces of wild triatomines captured in the same region, obtaining three positive
      results that were confirmed by microscopic examination. The 25 amplified products
      obtained in this study were then reamplified with primers that gave a final
      amplicon containing sequences from the most variable region of kDNA minicircles.
      These were used as probes in hybridization experiments aimed at defining the
      degree of relatedness between the strains infecting humans and insects based on
      kDNA homologies. We found that the amplification products from the three
      triatomines were related and showed no cross-hybridization with those obtained
      from human infections. Eight amplified products from human infections showed no
      cross-hybridization and did not hybridize with products from other patients. This
      indicates that the strains of T. cruzi circulating in the region present a high
      level of genetic heterogeneity. Finally, a number of amplified products
      hybridized with amplicons that did not hybridize with each other, indicating that
      infections with a parasite population presenting a mixed kDNA content (either due
      to different strains of T. cruzi or to a hybrid parasite) are a more frequent
      event than previously thought.

PMID- 8542988
TI  - Toxoplasma gondii: characterization of a monoclonal antibody recognizing antigens
      of 36 and 38 kDa with acid phosphatase activity located in dense granules and
      rhoptries.
AB  - Acid phosphatase activity in Toxoplasma gondii was studied by electron microscopy
      and found in the rhoptries and dense granules. On Western blots, six bands were
      found to have acid phosphatase activity; a double band of 36-38 kDa showed the
      strongest activity. In order to raise monoclonal antibodies to antigens of
      potential importance in parasite invasion of the host cell, mice were immunized
      with live T. gondii of the cyst-forming ME119 isolate and later boosted with
      tachyzoites of the RH strain. One of the monoclonal antibodies, S16, recognized
      the 36- to 38-kDa antigen. Immunogold labeling and electron microscopy showed
      that the antigens were located in dense granules and rhoptries. Using
      immunoprecipitation with S16, SDS-PAGE, IEF, and Western blotting, we show that
      the 36- to 38-kDa rhoptry antigen recognized by S16 has acid phosphatase
      activity.

PMID- 8542989
TI  - Leishmania amazonensis: multidrug resistance in vinblastine-resistant
      promastigotes is associated with rhodamine 123 efflux, DNA amplification, and RNA
      overexpression of a Leishmania mdr1 gene.
AB  - A vinblastine-resistant Leishmania amazonensis cell line (RV100) which exhibits
      cross-resistance to the unrelated drug adriamycin, and thus is considered to be
      multidrug resistant (MDR), was isolated after stepwise selection with increasing
      concentrations of vinblastine. This phenotype was partially reverted by the
      calcium channel antagonist verapamil. Drug transport studies using the
      hydrophobic fluorescent dye rhodamine 123 demonstrated that the MDR cell line has
      a reduced dye accumulation due to an increased efflux. Furthermore, DNA and RNA
      hybridization studies demonstrated that a gene (lamdr1), homologous to ldmdr1 and
      lemdr1, was overexpressed and amplified within 27 kb extrachromosomal DNA circles
      (V-circles) in these cells. An independent cell line, RA5000, which was selected
      for resistance to adriamycin and was not cross-resistant to vinblastine,
      accumulated normal levels of rhodamine 123 and did not contain amplified DNA or
      overexpressed RNA of mdr-related sequences.

PMID- 8542990
TI  - Babesia bigemina: identification of B cell epitopes associated with parasitized
      erythrocytes.
AB  - Rhoptries are involved in host cell invasion and rhoptry polypeptides, including
      the Babesia bigemina rhoptry-associated protein-1 (RAP-1), are targets for
      protective immune responses. Polyclonal antisera produced against isolated
      rhoptries is directed predominantly against RAP-1 and reacts with both the
      merozoite and the membrane of parasitized erythrocytes. To determine whether
      these B cell epitopes associated with the parasitized erythrocyte are derived
      from RAP-1 or, alternatively, from previously undetected merozoite polypeptides,
      monoclonal antibodies (mAbs) were generated from mice immunized with rhoptries
      isolated from the JG-29 clone of the Mexico strain. The anti-RAP-1 mAbs bound
      only merozoites in a punctate immunofluorescence pattern. A second group of four
      mAbs, none of which were reactive with RAP-1, bound the parasitized erythrocyte.
      Two of these latter mAbs, 64/44.17.3 and 64/05.7.2, reacted only with parasitized
      erythrocytes that had been permeabilized. MAb 64/44.17.3 bound a 54-kDa merozoite
      polypeptide while 64/05.7.2 bound a > or = 225-kDa merozoite polypeptide. MAbs
      64/32.8.5 and 64/38.5.3 recognized epitopes on 17.5- and 76-kDa polypeptides
      exposed on the external surface of intact parasitized erythrocytes. The results
      indicate that the identified RAP-1 epitopes are not associated with the
      erythrocyte cytoskeleton or membrane and that anti-RAP-1 immunity is most likely
      generated against the free merozoite. All new mAbs reacted with every B. bigemina
      strain tested (Mexico, Puerto Rico, St. Croix, Texcoco, Jaboticabal). The
      conservation of RAP-1 epitopes among these strains supports the continued testing
      of RAP-1 as a vaccine component. In addition, the identification of epitopes
      expressed on the surface of erythrocytes infected with all five strains provides
      new candidate immunogens.

PMID- 8542991
TI  - The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of
      nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide
      stimulated macrophages.
AB  - To investigate the effect of the heme moiety of malaria pigment, hemozoin, on
      phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the
      synthetic heme-polymer chemically identical to the native pigment, or the soluble
      monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1),
      tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the
      supernatants after stimulation with lipopolysaccharide. The results indicate that
      both beta-hematin and hematin induce a dose-dependent inhibition of macrophage
      production of TNF alpha and NO, but not of IL1. One-hour pretreatment with
      soluble hematin inhibited production of cytotoxic mediators by more than 50%
      compared to controls, while 6-hr exposure was necessary for insoluble beta
      hematin to induce the same level of inhibition. However, the same treatment did
      not modify the production of TNF alpha and NO by mouse microglia cell lines. The
      inhibition was partially counterbalanced by adding sulphydryl group donors such
      as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation
      time. The results of the present study confirm the inhibitory role of malaria
      pigment and show that such effect is due to the heme moiety and may be selective
      for the production of cytotoxic mediators by specific phagocytes. The
      implications of these findings in the control of malaria infection and disease
      and in the pathogenesis of severe malaria are discussed.

PMID- 8542992
TI  - Use of the Bo-RBC-SCID mouse model for isolation of a Babesia parasite from
      grazing calves in Japan.
AB  - SCID mice with circulating bovine red blood cells (Bo-RBC-SCID mice) were used to
      isolate Babesia parasites from grazing calves in Japan. Although the initial
      blood samples obtained from the calves contained both Babesia and Theileria
      parasites, we were able to isolate only the Babesia parasites by repeated blood
      passages in Bo-RBC-SCID mice, taking advantage of the much more rapid growth of
      Babesia than of Theileria. The parasites isolated had characteristics of large
      type Babesia, showing typical paired pyriform morphology. The Bo-RBC-SCID mice
      infected with the Babesia parasites developed a high level of parasitemia,
      showing severe clinical symptoms characterized by hemoglobinuria, jaundice, and
      hemolytic anemia. In addition, some mice exhibited nervous symptoms, particularly
      paralysis of both posterior limbs. The results demonstrated that the Bo-RBC-SCID
      mouse model was useful not only for isolating Babesia from cattle but also for
      studying the disease caused by the Babesia infection.

PMID- 8542993
TI  - Crithidia luciliae: effect of purine starvation on S-adenosyl-L-methionine uptake
      and protein methylation.
AB  - The utilization of S-adenosyl-L-[methyl-3H]methionine ([3H-methyl]AdoMet) by
      Crithidia luciliae was assessed under nutrient-replete and purine-starvation
      conditions. Uptake experiments with intact cells demonstrated that the radiolabel
      from this molecule was accumulated by purine-starved organisms at a rate
      approximately 10-fold greater than that observed in those cultivated in nutrient
      replete medium. Purine-starved cells also incorporated the radiolabel into
      trichloroacetic acid insoluble material at an approximately 10-fold faster rate
      than nutrient-replete cells. No differences, however, were observed in the
      intracellular levels of AdoMet and its metabolites between organisms cultivated
      under the two conditions. Results of comparative labeling studies with [3H
      methyl]AdoMet, S-adenosyl-L-[carboxyl-14C]methionine, L-[methyl-3H]methionine and
      L-[35S]methionine in the presence and absence of cycloheximide demonstrated that
      the incorporation of label from [3H-methyl]AdoMet was due to transmethylation and
      was independent of protein synthesis. Further, approximately 15 methylated
      protein bands were identified by SDS-PAGE analysis. Lysates from both purine
      starved and nutrient-replete organisms demonstrated similar levels of activity of
      three protein methyltransferases (PMI, II, III). The differences observed in [3H
      methyl]AdoMet utilization between purine-starved and nutrient-replete C. luciliae
      may reflect the enhanced purine transport capacity which results from purine
      starvation.

PMID- 8542994
TI  - Trypanosoma cruzi: interruption of both alleles of a gene encoding a protein
      containing 14-amino-acid repeats by targeted insertion of NEOr and HYGr.
AB  - In Trypanosoma cruzi approximately 90% of the 121- and 176-kDa cytoskeletal
      proteins encoded by the two alleles of the TCR27 gene is composed of 14-amino
      acid repeats. To gain insight into the function of the TCR27 proteins we replaced
      the corresponding regions of 42-nucleotide repeats in the two alleles with the
      NEOr and HYGr genes. Analyses of DNAs and RNAs from four clones resistant to both
      G418, a neomycin analogue, and hygromycin showed that in both cases the
      repetitive regions had in fact been deleted. In addition, the absence of
      expression of the 14-amino-acid repeats was confirmed in Western blots. In axenic
      cultures growth rates of the morphologically unchanged, doubly resistant
      organisms were not different from those of wild-type parasites. However, the
      doubly resistant organisms proliferated more slowly in cultured mammalian cells
      than did wild-type parasites. These findings indicate that the absence of the
      TCR27 repetitive regions is detrimental, but not fatal, to the parasites.

PMID- 8542995
TI  - Immunological characterization and expression in Escherichia coli and baculovirus
      systems of a Trypanosoma vivax antigen detected in the blood of infected animals.
AB  - A monoclonal antibody (MAb)Tv27 employed in an antigen-detection enzyme
      immunosorbent assay (Ag-ELISA) for diagnosis of Trypanosoma vivax infection was
      shown to react with a T. vivax-specific protein of an approximate molecular
      weight of 10 kDa. This protein is diffusely distributed throughout the cytosol
      and nucleus of metacyclic forms, bloodstream forms, and procyclic-like elongated
      trypomastigotes, but is not detectable in epimastigotes of T. vivax. The T. vivax
      specific antigen prepared from parasite lysates appeared to be of lower molecular
      mass than the form expressed in either Escherichia coli or in baculovirus
      infected silkworm insect cells. In the recombinant baculovirus-infected cells,
      the protein was expressed mostly as an 18-kDa peptide with less abundant forms of
      13 and 12 kDa, while the protein expressed in E. coli was approximately 14 kDa.
      Both the low- and higher-molecular-weight proteins are recognized by the MAb Tv27
      in Western blots and in Ag-ELISA. Although the crude preparations of the protein
      produced by the insect cells are labile when kept for more than 2 hr at 24
      degrees C, they retained reactivity at temperatures below 4 degrees C for several
      weeks. The proteins expressed in both the insect cells and E. coli captured anti
      T. vivax antibodies in sera prepared from trypanosome-infected animals. Since the
      recombinant protein expressed in the baculovirus-infected cells is available in
      large homogeneous quantities, it would serve as a positive control in Ag-ELISA
      and is also usable for antibody detection assays.

PMID- 8542996
TI  - Echinococcus granulosus: partial characterization of the conductive properties of
      two cation channels from protoscoleces of the ovine strain, reconstituted on
      planar lipid bilayers.
AB  - Two cationic channels present in the microsomal fraction from Echinococcus
      granulosus protoscoleces of the sheep strain were studied in planar bilayer
      reconstitution experiments. A whole-worm homogenate was subjected to differential
      centrifugation and the postmitochondrial supernatant was laid on the top of a
      discontinuous sucrose gradient. The 15-30% (w/v) membrane fraction, enriched in
      NADPH-cytochrome c reductase, exhibited the highest fusion rate, two cationic
      channels being most frequently reconstituted. Both of them were highly cation
      selective and had high conductances (244 and 107 pS in symmetrical 150 mM KCl).
      In most experiments, none of them displayed voltage dependence. The 244-pS
      channel was activated by Ca2+ and blocked by Ba2+, both in the micromolar range,
      thus partially resembling the Ca(2+)-activated K+ channel from more highly
      evolved animals. The 107-pS channel exhibited a Cs+ approximately equal to K+ >
      Na+ > Li+ > Ca2+ selectivity sequence (as measured by permeability ratios) and,
      most frequently, a high open probability (> 0.9) irrespective of the experimental
      conditions used, therefore sharing many properties of Schistosoma mansoni outer
      tegumental membrane cation channels.

PMID- 8542997
TI  - Plasmodium falciparum: recrudescence of parasites in culture.
AB  - The basis of recrudescence, the reappearance of malaria parasites after
      chemotherapy or after failure of immune suppressions of the parasites, was
      studied in cultures of Plasmodium falciparum. When the cultured parasites were
      exposed eight times over a 4-day period to 5% D-sorbitol, which destroyed
      infected RBCs containing trophozoites or schizonts, they showed recrudescence
      several days after cessation of treatment. Pyrimethamine-sensitive parasites were
      cleared by 10(-6) M pyrimethamine; pyrimethamine-resistant parasites also were
      cleared by 10(-4) M pyrimethamine. Both groups of parasites underwent
      recrudescence in the same manner as those exposed to 5% D-sorbitol. These
      recrudescent parasites were found to be as susceptible to these treatments as
      were the parasites before treatment. Therefore, our results strongly suggest that
      a subpopulation of the parasites escapes the effect of drugs by a mechanism other
      than drug resistance.

PMID- 8542998
TI  - Trypanosoma cruzi: exposure of murine cells to live parasites in vitro leads to
      enhanced surface class I MHC expression which is type I interferon-dependent.
AB  - Previous reports indicate that myocardial cells from human patients with chronic
      Chagasic cardiomyopathy express increased levels of class I MHC molecules on
      their surfaces. To determine whether parasites can modulate class I expression,
      we have examined the effect of in vitro exposure to live Trypanosoma cruzi
      trypomastigotes on class I MHC expression by murine cells. Here we show that co
      incubation of various murine cell lines, including 3T3 fibroblasts, J774.A1
      macrophage-like cells, and freshly-explanted BALB/c primary embryo fibroblasts,
      with live trypomastigotes leads to a two- to fourfold increase in their
      expression of surface class I MHC molecules. Cell-free supernatants from T. cruzi
      exposed cells, but not from either cells or parasites cultured alone, were also
      capable of upregulating class I expression, indicating the involvement of a
      soluble factor. Active supernatants were shown to contain IFN-alpha/beta activity
      and their ability to upregulate class I was inhibitable by anti-IFN-alpha/beta
      Abs. This ability of T. cruzi to enhance class I MHC expression on host cells via
      IFN-alpha/beta induction could be an important factor in the initiation of host
      immunity and/or immune-mediated pathology.

PMID- 8542999
TI  - Oesophagostomum dentatum: population dynamics and synthesis of prostanoids by
      histotropic stages cultured in vitro.
AB  - The dynamics of production and excretion of prostanoids by histotropic larvae of
      Oesophagostomum dentatum and the role of prostanoids for the development of O.
      dentatum were studied under in vitro conditions. In control cultures fourth stage
      larvae (L4) were first seen on Day 7 of in vitro cultivation. Their numbers
      steadily increased until Day 21 of in vitro cultivation. Thereafter, the numbers
      of L4 no further increased. The continuous presence of inhibitors of prostanoid
      synthesis such as acetylsalicyclic acid (ASA, 5.6 mmole/liter) or indomethacin
      (INDO, 1.4 mmole/liter) in the culture medium blocked the development to L4
      almost completely. When ASA was given first on Day 13 of in vitro cultivation L4
      counts still increased during the following 4 days. However, the numbers of
      larvae which reached the L4 stage in these cultures was reduced to 65% of that in
      control cultures. Resumption of development to L4 was seen after the withdrawal
      of INDO in cultures treated with this drug until Day 13 of in vitro cultivation.
      Larvae and supernatants were collected separately on Days 7, 14, 21, or 28 of in
      vitro cultivation and larvae were homogenized. The presence of prostaglandin (PG)
      E2, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane (TX) B2 was assayed
      radioimmunologically in homogenates and supernatants. In the homogenates only
      PGE2 and PGD2 were regularly detected. The total amount of PGE2 and PGD2 in the
      homogenates significantly increased with the increase in L4 numbers, whereas the
      homogenate protein-based values did not. In addition to PGD2 and PGE2, PGF2 alpha
      and TXB2 were found in the supernatants. PGE2 accounted for about 50% of the
      prostanoids in the supernatants on Day 7 of in vitro cultivation but was
      generally absent thereafter. After 14, 21, and 28 days of in vitro cultivation
      TXB2 was the most prominent single prostanoid in the supernatants. PGD2 was found
      in the supernatants only after 7 and 28 days of in vitro cultivation. PGF2 alpha
      was present in decreasing amounts in the supernatants throughout the cultivation
      period. In conclusion, histotropic larvae of O. dentatum produce and excrete
      mediators of the prostanoid type which may serve as endogenous hormone-like
      growth factors.

PMID- 8543000
TI  - Schistosoma: rate of glucose import is altered by acetylcholine interaction with
      tegumental acetylcholine receptors and acetylcholinesterase.
AB  - The blood dwelling stages of schistosomes have acetylcholinesterase (AChE) and
      nicotinic-like acetylcholine receptors (nAChR) on their teguments. Both AChE and
      nAChR are concentrated on the dorsal surface of the adult male, a major surface
      for nutrient uptake for the worm pair. Exposure of tegumental AChE and nAChR to
      acetylcholine (ACh), the natural ligand of these molecules, has a consequence for
      the transporting function of this membrane in some schistosome species. The rate
      of glucose uptake in vitro by Schistosoma haematobium and Schistosoma bovis adult
      worm pairs was enhanced by approximately 60% at blood concentrations of ACh.
      Schistosoma mansoni did not show a similar response. The specificity of the ACh
      interaction with nAChR and AChE was shown by ablation of the effect with specific
      antagonists of nAChR (d-tubocurarine and alpha-bungarotoxin) and an inhibitor of
      AChE (BW284C51). The primary effect occurs on the tegument since alpha
      bungarotoxin and BW284C51 do not penetrate the schistosome tegument. The species
      differences in reliance on this mechanism are consistent with their relative
      sensitivities to the AChE inhibitory drug, metrifonate.

PMID- 8543001
TI  - Molecular cloning and characterization of the filarial LIM domain proteins AvL3-1
      and OvL3-1.
AB  - A full-length cDNA of the filarial nematode Acanthocheilonema viteae was isolated
      from a cDNA library of female worms, using a partial cDNA of the OvL3-1 gene of
      Onchocerca volvulus as a probe. The AvL3-1 cDNA contained an open reading frame
      which encoded for a protein with a theoretical molecular weight of 64 kDa. The
      deduced protein contained a predicted signal sequence, a short repetitive motive
      of unknown function, and three LIM domains. The structure of the LIM domains was
      identical to those of zyxin, a cytoskeleton-associated protein of chicken
      fibroblasts, suggesting that AvL3-1 has a similar role in filarial nematodes. The
      sequence information was used to isolate the homologous cDNA of O. volvulus by
      PCR from a cDNA library of female O. volvulus, which showed an overall identity
      of 76.9% to AvL3-1 on the protein level. AvL3-1 was expressed in Escherichia coli
      and the affinity-purified fusion free protein was used to immunized jirds
      (Meriones unguiculatus). Immunization together with the adjuvant STP or with
      Freund's adjuvant induced IgG and IgM antibody responses, but no significant
      protection against a challenge infection with L3 of A. viteae, compared to
      appropriate control groups.

PMID- 8543002
TI  - Plasmodium yoelii: expression of circumsporozoite protein and sporozoite surface
      protein 2 by sporozoites in culture.

PMID- 8543003
TI  - Taenia crassiceps: cloning and mapping of mitochondrial DNA and its application
      to the phenetic analysis of a new species of Taenia from Southeast Asia.

PMID- 8543004
TI  - Heat shock does not increase the transcriptional efficiency of the Hsp 70 genes
      of Trypanosoma brucei.

PMID- 8543005
TI  - Toxoplasma gondii: parasiticidal effects of bovine lactoferricin against
      parasites.

PMID- 8543006
TI  - Trypanosoma brucei: stimulation of adenylate cyclase by proventriculus and
      esophagus tissue of the tsetse fly, Glossina morsitans morsitans.

PMID- 8543007
TI  - Trichuris ovis and Trichuris globulosa: morphological, biometrical, and genetic
      studies.

PMID- 8543008
TI  - Expression of poliovirus 2Apro in mammalian cells: effects on translation.
AB  - Poliovirus protease 2Apro has been efficiently expressed in HeLa and COS cells
      upon transfection with vector pTM1-2A and infection with the recombinant vaccinia
      virus bearing the T7 RNA polymerase. The expressed poliovirus protease localizes
      to the cytoplasm of the transfected cells, both in the endoplasmic reticulum and
      in vesicles scattered in the cytoplasm. Cleavage of p220, a component of
      initiation factor eIF-4F, selectively occurs from 5 h post-infection in
      transfected cells infected with the recombinant virus. This cleavage correlates
      in time with the profound inhibition observed in the synthesis of vaccinia virus
      proteins. A similar blockade of vesicular stomatitis virus translation takes
      place upon 2Apro expression. Finally, the synthesis of poliovirus protein 2C from
      a recombinant vaccinia virus that expresses this protein under the EMC
      untranslated leader region is not affected by the synthesis of 2Apro. These
      findings lend support to the idea that translation of capped mRNAs requires the
      integrity of p220, while this requirement is not observed when translation of a
      mRNA bearing a picornavirus leader region is assayed.

PMID- 8543009
TI  - ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride
      channel family.
AB  - We cloned two novel members of the CLC chloride channel family from rat and human
      brain. ClC-6 is a 97-kDa protein, and ClC-7 a 89-kDa protein roughly 45%
      identical with ClC-6. Together they define a new branch of this gene family. Both
      genes are very broadly expressed, e.g. in brain, testes, muscle and kidney. In
      mouse embryos, both genes are expressed as early as day 7. While the human gene
      for ClC-6 is located on human chromosome 1p36 and shares this region with hClC-Ka
      and hClC-Kb, ClC-7 is on 16p13. ClC-6 has a highly conserved glycosylation site
      between transmembrane domains D8 and D9, while ClC-7 is the only known eukaryotic
      ClC protein which lacks this site. Hydropathy analysis indicates that domain D4
      cannot serve as a transmembrane domain. Both ClC-6 and ClC-7 cannot be expressed
      as chloride channels in Xenopus oocytes, either singly or in combination.

PMID- 8543010
TI  - Stimulatory effect of ouabain on VCAM-1 and iNOS expression in murine endothelial
      cells: involvement of NF-kappa B.
AB  - Endothelial cells play a pivotal role in the development of atherosclerosis. An
      'activated' phenotype of these cells is manifested by signal transduction
      dependent expression of genes encoding cytokines, pro- and anticoagulant factors,
      and cell adhesion molecules. In the current study we examined the effect of
      ouabain, an inhibitor of Na+/K(+)-ATPase, on the process of endothelial cell
      activation. We demonstrated that ouabain was able to stimulate VCAM-1 expression
      and potentiate the effect of IFN-gamma on this process. Moreover, ouabain
      provided a complementary signal for either TNF or IFN-gamma in inducing iNOS
      expression. Our data also show, for the first time, that inhibition of Na+/K(+)
      ATPase led to activation of the transcription factor, NF-kappa B, which may
      provide an explanation for the effects of ouabain on endothelial cells.

PMID- 8543011
TI  - S-phase phosphorylation of lamin B2.
AB  - Lamin B2 modification in synchronously dividing populations of human diploid
      fibroblasts was determined by 2-dimensional gel electrophoresis and
      [32P]orthophosphate labelling. In quiescent (G0) and G1 cultures of HDF, lamin B2
      migrated as 2 spots on 2-dimensional gels. In contrast, in S-phase populations of
      HDF lamin B2 migrated as a single basic species. The level of lamin B2
      phosphorylation was determined after immunoisolation from [32P]orthophosphate
      labelled cells. The results of these experiments indicated a 2-3-fold increase in
      the steady state level of lamin B2 phosphorylation in S-phase HDF compared with
      G0 HDF. Consistent with this evidence, tryptic peptide maps revealed the presence
      of a phosphopeptide in S-phase lamin B2 which was absent from G0 lamin B2. Since
      all of the phosphate incorporated into S-phase and G0 lamin B2 was recovered in
      serine residues we conclude that the S-phase specific phosphopeptide did not
      represent either of the cdc2 sites associated with entry nuclear lamina
      breakdown.

PMID- 8543012
TI  - Thapsigargin discriminates strongly between Ca(2+)-ATPase phosphorylated
      intermediates with different subcellular distributions in bovine adrenal
      chromaffin cells.
AB  - We studied the effects of thapsigargin on the formation of the phosphorylated
      intermediates (E approximately Ps) of endoplasmic reticulum Ca(2+)-ATPases in
      microsomes from bovine adrenal medulla. When submicrosomal fractions were
      separated on a sucrose gradient, two components of 100 kDa Ca(2+)-ATPase E
      approximately P displaying distinct subcellular distributions were resolved. The
      first component was defined by Ca(2+)-induced protection against thapsigargin
      inhibition. The second component did not display such protection, with a 3 orders
      of magnitude difference in thapsigargin inhibitory potency towards the 2
      components. In the absence of Ca2+, both E approximately P components were highly
      sensitive to thapsigargin inhibition, revealing the presence of high-affinity
      thapsigargin-binding sites characteristic of SERCA ATPases. These data
      demonstrate a new level of molecular heterogeneity among Ca(2+)-ATPases of
      endoplasmic reticulum, and provide the first evidence of differential subcellular
      localization of individual Ca2+ pump subtypes in cells of neural origin.

PMID- 8543013
TI  - A rainbow trout SRY-type gene expressed in pituitary glands.
AB  - A Sox (SRY-type HMG box) gene, designated SoxP1, was isolated from a cDNA library
      made from pituitaries of immature rainbow trout. Sequence analysis indicated that
      the cDNA had an open reading frame encoding 467 amino acid residues containing a
      DNA binding motif, known as the high mobility group (HMG) box. Northern blot
      analysis showed trout SoxP1 mRNA was detected in pituitaries and gonadal tissues,
      but not in liver, spleen, and heart. In pituitaries, trout SoxP1 mRNA was more
      abundant in immature fish than in mature fish. Gel shift retardation analysis
      indicated that the recombinant HMG box protein of SoxP1 produced in E. coli had a
      DNA binding property for an AACAAT or AACAAAG sequence. These findings suggest
      that the trout SoxP1 protein may play certain roles in growth or maturation in
      pituitaries as a transcription factor.

PMID- 8543014
TI  - The 65-kDa protein derived from the internal translational start site of the clpA
      gene blocks autodegradation of ClpA by the ATP-dependent protease Ti in
      Escherichia coli.
AB  - The ATP-dependent protease Ti consists of two different components: ClpA
      containing ATP-cleaving sites and ClpP having serine active sites for
      proteolysis. The clpA gene has dual translational start sites and therefore
      encodes two polypeptides with sizes of 84 and 65 kDa (referred to as ClpA84 and
      ClpA65, respectively). Here we show that ClpA84, but not ClpA65, is degraded in
      vitro by ClpP in the presence of ATP. The ClpP-mediated hydrolysis of ClpA84
      could be prevented by casein, which is an excellent substrate of protease Ti
      (i.e. ClpA84/ClpP complex). Thus, it appears that free form of ClpA84 competes
      with casein for the degradation by ClpA/ClpP complex. Furthermore, ClpA65
      inhibited the auto-degradation of ClpA84 by the complex. These results suggest
      that ClpA65 may play an important role in the control of the ClpA84 level and in
      turn in the regulation of ATP-dependent protein breakdown in E. coli.

PMID- 8543015
TI  - Mg2+ activation of Escherichia coli inorganic pyrophosphatase.
AB  - Further refinement of X-ray data on Escherichia coli inorganic pyrophosphatase
      [Oganessyan et al. (1994) FEBS Lett. 348, 301-304] to 2.2 A reveals a system of
      noncovalent interactions involving Tyr55 and Tyr141 in the active site. The pKa
      for one of the eight Tyr residues in wild-type pyrophosphatase is as low as 9.1
      and further decreases to 8.1 upon Mg2+ binding, generating characteristic changes
      in the absorption spectrum. These effects are lost in a Y55F but not in a Y141F
      variant. It is suggested that the lower-affinity site for Mg2+ in the enzyme is
      formed by Tyr55 and Asp70, which are in close proximity in the apo-enzyme
      structure.

PMID- 8543016
TI  - Betaine is an osmolyte in RAW 264.7 mouse macrophages.
AB  - Hyperosmotic (405 mosmol/l) exposure of RAW 264.7 mouse macrophages led to a
      stimulation of betaine uptake and an increase in betaine transporter (BGT-1) mRNA
      levels. Conversely, hypoosmotic (205 mosmol/l) exposure decreased betaine uptake
      and diminished BGT-1 mRNA levels. Betaine uptake was Na(+)-dependent and was
      inhibited by about 90% by GABA, whereas inhibition by methylaminoisobutyrate and
      myoinositol was less than 15%. Addition of betaine strongly diminished BGT-1 mRNA
      levels in cells exposed to normoosmotic or hyperosmotic media. When mouse
      macrophages were preloaded with betaine, lowering of the extracellular osmolarity
      was followed by a rapid betaine efflux from the cells. This study identifies a
      constitutively expressed and osmosensitive betaine transporter in RAW 264.7
      macrophages and the use of betaine as an osmolyte in these cells.

PMID- 8543017
TI  - Fibroblasts transformed by combinations of ras, myc and mutant p53 exhibit
      increased phosphorylation of histone H1 that is independent of metastatic
      potential.
AB  - H1 histones play an important role in regulating higher order structure of
      chromatin and are potential regulators of gene expression. H1s are
      phosphorylated, a modification which alters their interaction with DNA. We
      measured the abundance of three phosphorylated H1 subtypes in mouse fibroblasts
      transformed by combinations of ras, myc and mutant p53 which differ in metastatic
      potential. We found that there is an increase in phosphorylation of H1 subtypes
      in fibroblasts transformed with ras, myc and mutant p53. This increase was found
      to correlate with cellular transformation but not with induction of the
      metastatic phenotype.

PMID- 8543018
TI  - Expression of cDNA for a bark lectin of Robinia in transgenic tobacco plants.
AB  - A cDNA encoding a bark lectin of Robinia pseudoacacia was introduced into tobacco
      plants. The expression of the lectin cDNA under control of the 35S promoter was
      confirmed by Western blot analysis and a hemagglutination assay of extracts of
      transgenic plants. Western blot analysis revealed that the subunit of the lectin
      from tobacco had a molecular mass of 29 kDa. The sequence of nine amino acids
      from the N-terminus of the lectin from transgenic tobacco plants was identical to
      that of the bark lectin from Robinia, indicating that the lectin had been
      processed correctly at its N-terminus in tobacco. The molecular mass of the
      purified native lectin produced by tobacco plants was estimated to be 112 kDa by
      gel filtration on a column of Superdex 200. It is suggested that the lectin
      subunits assembled to form tetramers in transgenic tobacco plants.

PMID- 8543019
TI  - Interaction of cryptophycin 1 with tubulin and microtubules.
AB  - The cryptophycins are newly discovered antimitotic agents isolated from the
      cyanobacterium Nostoc. Previous studies using cultured cells demonstrated that
      microtubules are the target of these compounds. We have studied the interaction
      of cryptophycin 1 with tubulin and microtubules in vitro. Cryptophycin 1 is an
      effective inhibitor of tubulin polymerization, causes tubulin to aggregate, and
      depolymerizes microtubules to linear polymers somewhat similar to the spiral-like
      structures produced by the Vinca alkaloids. Cryptophycin 1 also inhibits
      vinblastine binding to tubulin but not colchicine binding. Thus, it appears that
      the cryptophycins may bind to the Vinca site in tubulin or to a site that
      overlaps with the Vinca site.

PMID- 8543020
TI  - Close evolutionary relatedness among functionally distantly related members of
      the (alpha/beta)8-barrel glycosyl hydrolases suggested by the similarity of their
      fifth conserved sequence region.
AB  - A short conserved sequence equivalent to the fifth conserved sequence region of
      alpha-amylases (173_LPDLD, Aspergillus oryzae alpha-amylase) comprising the
      calcium-ligand aspartate, Asp-175, was identified in the amino acid sequences of
      several members of the family of (alpha/beta)8-barrel glycosyl hydrolases.
      Despite the fact that the aspartate is not invariantly conserved, the stretch can
      be easily recognised in all sequences to be positioned 26-28 amino acid residues
      in front of the well-known catalytic aspartate (Asp-206, A. oryzae alpha-amylase)
      located in the beta 4-strand of the barrel. The identification of this region
      revealed remarkable similarities between some alpha-amylases (those from Bacillus
      megaterium, Bacillus subtilis and Dictyoglomus thermophilum) on the one hand and
      several different enzyme specificities (such as oligo-1,6-glucosidase,
      amylomaltase and neopullulanase, respectively) on the other hand. The most
      interesting example was offered by B. subtilis alpha-amylase and potato
      amylomaltase with the regions LYDWN and LYDWK, respectively. These observations
      support the idea that all members of the family of glycosyl hydrolases adopting
      the structure of the alpha-amylase-type (alpha/beta)8-barrel are mutually closely
      related and the strict evolutionary borders separating the individual enzyme
      specificities can be hardly defined.

PMID- 8543021
TI  - Cloning and expression in Escherichia coli of cDNA encoding house dust mite
      allergen Der f 3, serine protease from Dermatophagoides farinae.
AB  - Der f 3 is one of the allergens produced by house dust mite Dermatophagoides
      farinae showing serine protease activity. Based on its amino acid sequence, a
      cDNA clone encoding Der f 3 was isolated from a cDNA library of D. farinae.
      Sequencing analysis of the clone revealed the presence of an open reading frame
      of 780 bp, which encodes a mature protein of 232 amino acids with 27 amino acids
      of pre-pro sequence at the N-terminus. When proDer f 3 was produced in
      Escherichia coli as a fused protein with glutathione-S-transferase, the fused
      protein was accumulated as inclusion bodies. The protein purified with 8 M urea
      and glutathione-affinity column chromatography, however, did not show protease
      activity. When an arginine residue was introduced at the C-terminus of the pro
      region in place of threonine, removal of the pro-region to produce an active
      mature protease was observed. The specificity and the activity of this
      recombinant protease were almost the same as those of native Der f 3.

PMID- 8543022
TI  - The Gag polypeptides of the Drosophila 1731 retrotransposon are associated to
      virus-like particles and to nuclei.
AB  - 1731 is a Drosophila melanogaster retrotransposon whose nucleotide sequence shows
      a proviral architecture with two long terminal repeats (LTRs) framing two
      internal Open Reading Frames (ORFs). The pol ORF2 of this mobile genetic element
      was demonstrated to code for an active Reverse Transcriptase (RT) and the ORF1 is
      expected to code for the structural Gag proteins of the virus-like particles
      (VLP). Using specific anti-Gag antibodies, we have characterized the 1731 Gag
      polypeptides expressed either in vitro or in Kc Drosophila melanogaster cultured
      cells. Together with the 1731 RT, the largest, likely post-translationaly
      modified Gag polypeptides are gathered into cytoplasmic virus-like particles.
      Moreover and consistent with the nuclear localization signal present in the Gag
      sequence, we observed that a short 1731 Gag polypeptide is associated to the cell
      nuclei.

PMID- 8543023
TI  - Cloning and characterisation of the rabbit 5-HT1D alpha and 5-HT1D beta
      receptors.
AB  - The genes encoding the rabbit 5HT1D alpha and 5HT1D beta receptors have been
      cloned. The deduced amino acid sequence of these receptors shows 91-92% amino
      acid sequence identity with their human homologues, and similar high sequence
      identity with homologues from other species. The receptors were transiently
      expressed in COS-7 cells and exhibit a pharmacological profile closely resembling
      their human homologues, including a higher affinity of ketanserin for the 5-HT1D
      alpha subtype. However, sumatriptan had a lower affinity for both the rabbit
      receptors compared to their human counterparts. This may be accounted for by
      differences between the primary amino acid sequences of these species homologues.

PMID- 8543024
TI  - A three-dimensional structure model of the complex of glutamyl-tRNA synthetase
      and its cognate tRNA.
AB  - A docking model of glutamyl-tRNA synthetase (GluRS) and tRNAGlu was constructed,
      on the basis of the distinguished similarity between the X-ray crystallographic
      three-dimensional structures of the N-terminal halves of the Thermus thermophilus
      GluRS in the free state and the Escherichia coli glutaminyl-tRNA synthetase in a
      complex with tRNAGln. The modeled structure is energetically favorable and is
      also well consistent with the results of site-directed mutagenesis studies. The
      model indicates that the GluRS-specific insertions 2 and 3 fit and bind to the
      acceptor stem and the D arm, respectively, of the cognate tRNA without affecting
      other contacts. In particular, insertion 3 strongly interacts with the two D-stem
      base pairs that are essential for the tRNA-GluRS recognition.

PMID- 8543025
TI  - Two novel classes of neuroactive fatty acid amides are substrates for mouse
      neuroblastoma 'anandamide amidohydrolase'.
AB  - The endogenous cannabimimetic substance, anandamide (N-arachidonoyl-ethanolamine)
      and the recently isolated sleep-inducing factor, oleoyl-amide (cis-9,10
      octadecenoamide), belong to two neuroactive fatty acid amide classes whose action
      in mammals has been shown to be controlled by enzymatic amide bond hydrolysis.
      Here we report the partial characterisation and purification of 'anandamide
      amidohydrolase' from membrane fractions of N18 neuroblastoma cells, and provide
      evidence for a further and previously unsuspected role of this enzyme. An
      enzymatic activity catalysing the hydrolysis of [14C]anandamide was found in both
      microsomal and 10,000 x g pellet fractions. The latter fractions, which displayed
      the highest Vmax for anandamide, were used for further characterisation of the
      enzyme, and were found to catalyse the hydrolysis also of [14C]oleoyl-amide, with
      an apparent Km of 9.0 +/- 2.2 microM. [14C]anandamide- and [14C]oleoyl-amide
      hydrolysing activities: (i) exhibited identical pH- and temperature-dependency
      profiles; (ii) were inhibited by alkylating agents; (iii) were competitively
      inhibited by the phospholipase A2 inhibitor arachidonyl-trifluoromethyl-ketone
      with the same IC50 (3 microM); (iv) were competitively inhibited by both
      anandamide (or other polyunsaturated fatty acid-ethanolamides) and oleoyl-amide.
      Proteins solubilised from 10,000 x g pellets were directly analysed by
      isoelectric focusing, yielding purified fractions capable of catalysing the
      hydrolysis of both [14C]anandamide and [14C]oleoyl-amide. These data suggest that
      'anandamide amidohydrolase' enzymes, such as that characterised in this study,
      may be used by neuronal cells also to hydrolyse the novel sleep-inducing factor
      oleoyl-amide.

PMID- 8543026
TI  - Phorbol ester-induced suppression of leukotriene C4 synthase activity in human
      granulocytes.
AB  - The effect of the protein kinase C activator, phorbol 12-myristate 13-acetate
      (PMA), on the metabolism of exogenous leukotriene (LT)A4 in human granulocytes
      was investigated. After incubation with LTA4 decreased levels of LTC4 but not
      LTB4 were observed in granulocyte suspensions pretreated with PMA. This finding
      could in part be ascribed to oxidative metabolism of LTC4, since PMA induced a
      rapid degradation of exogenously added LTC4. After blocking of LTC4 metabolism
      with the H2O2 scavenger catalase, a PMA-provoked suppression of the conversion of
      LTA4 to LTC4 was observed, indicating PKC-dependent regulation of LTC4 synthase
      activity. This effect, as well as PMA-induced degradation of LTC4 was prevented
      by specific protein kinase C inhibitors.

PMID- 8543027
TI  - Protease inhibitors block apoptosis at intermediate stages: a compared analysis
      of DNA fragmentation and apoptotic nuclear morphology.
AB  - The possible correlation between DNA digestion and changes in nuclear morphology
      in apoptosis was studied by blocking the apoptotic process at intermediate
      stages. The apoptogenic action of three drugs: etoposide, puromycin, tributyltin,
      was contrasted with protease inhibitors with different specificity on U937 cells.
      The inhibitors interfered with the development of the apoptotic features without
      shifting cell death to necrosis: treated cells showed abnormal morphologies,
      which could be recognized as intermediate stages of apoptosis; accordingly, DNA
      analysis showed an inhibitor-dependent block of the apoptotic DNA digestion. The
      comparison between size of DNA fragments and nuclear morphology suggested the
      following correlations: loss of normal nuclear shape with the appearance of a >
      or = 2 Mb DNA band; ongoing chromatin condensation with the progressive DNA
      digestion up to 50 kb; nuclear fragmentation with DNA laddering. Protease
      inhibitors in etoposide-treated cells did not allow the formation of 700-300 kb
      fragments, suggesting that they possibly derive from a cell-mediated effect.

PMID- 8543028
TI  - An antibody VH domain with a lox-Cre site integrated into its coding region:
      bacterial recombination within a single polypeptide chain.
AB  - Bacterial lox-Cre recombination within a single antibody VH domain was achieved
      through integration of a loxP site into its coding sequence. The 5' half of the
      VH gene, in which the H2 loop was replaced by a mutant loxP site, was fused to
      geneIII in an 'acceptor' fd-phage vector containing also a wild type loxP site.
      With a 'donor' plasmid vector harbouring the 3' half of the VH gene flanked by
      the same, differing loxP sites it recombined into a full-length VH with the loxP
      site-H2 loop. This VH was purified from bacterial periplasm, where it folded into
      a typical immunoglobulin domain. The system allows the generation of large VH
      repertoires using lox-Cre recombination.

PMID- 8543029
TI  - Human vascular smooth muscle cells express an estrogen receptor isoform.
AB  - In women, estrogen (E2) exerts a clinically relevant anti-atherogenic effect. The
      atheroprotective effects of E2 are mediated both by E2-induced changes in
      systemic factors and by direct effects of E2 on the blood vessel wall. In studies
      to characterize E2 signaling pathways in vascular smooth muscle cells (VSMC), we
      recently demonstrated that human VSMC express a functional estrogen receptor [1].
      In the present study, we applied a reverse transcription/PCR-based strategy to
      identify isoforms of the E2 receptor in human VSMC. We now report that in
      addition to the classical E2 receptor, human VSMC derived from both mammary
      artery and saphenous vein express an estrogen receptor isoform containing an in
      frame deletion of Exon 4 (ER delta 4). RNase protection assays confirm the
      presence of ER delta 4 message in VSMC and demonstrate it is nearly as abundant
      as the classical E2 receptor. Transient transfection experiments in VSMC and HeLa
      cells demonstrate that, in contrast to the classical 67 kDa nuclear-localized E2
      receptor, ER delta 4: (a) is a 55 kDa protein that is widely distributed
      throughout the cell; (b) does not transactivate an E2 response element-driven
      reporter plasmid in response to E2; and (c) does not modulate transactivation of
      the ERE-reporter by the classical (wild type) estrogen receptor. Thus, human VSMC
      express an E2 receptor isoform that does not appear to alter gene transcription.
      The presence of a novel isoform of the E2 receptor may have important
      implications for studies of E2-mediated signaling in VSMC.

PMID- 8543030
TI  - Insulin-dependent translocation of the small GTP-binding protein rab3C in cardiac
      muscle: studies on insulin-resistant Zucker rats.
AB  - The failure of insulin-regulated recruitment of the GLUT4 glucose transporter in
      cardiac muscle of obese Zucker rats is associated with alterations of the
      subcellular distribution of the small-molecular-mass GTP-binding protein rab4A.
      Here, we show by subcellular fractionation and Western blotting a translocation
      of the small-molecular-mass GTP-binding protein rab3C from microsomal membranes
      to plasma membranes in lean control rats following in vivo insulin stimulation.
      However, in cardiac muscle of obese animals no significant effect of the hormone
      on the subcellular distribution of rab3C was observed. In GLUT4-enriched membrane
      vesicles, obtained from cardiac microsomes of the obese group as well as of lean
      controls, rab3C was not detectable. It is suggested that the altered behaviour of
      rab3C may contribute to an impaired trafficking of GLUT4 in the insulin-resistant
      state.

PMID- 8543031
TI  - Identification of a regulatory phosphorylation site in the hinge 1 region of
      nitrate reductase from spinach (Spinacea oleracea) leaves.
AB  - Purified nitrate reductase (NR) from spinach leaves was phosphorylated in vitro
      by NR-inactivating kinase on Ser-543 which is located in the hinge 1 region
      between the molybdenum-cofactor and haem-binding domains. Phosphorylation of Ser
      543 allowed NR to be inhibited by the inhibitor, NIP. Degraded NR preparations in
      which a proportion of the subunits had lost 45 amino acids from the N-terminus
      during purification could be phosphorylated by NR kinase on Ser-543, but could
      not subsequently be fully inhibited by NIP, suggesting a role for the N-terminal
      tail of NR in NIP binding.

PMID- 8543032
TI  - Quantification of DNA damage and repair in amino acid auxotrophs and UV-sensitive
      mutants of Aspergillus nidulans using an ELISA.
AB  - An ELISA used to investigate DNA repair in mammalian cells has been adapted to
      investigate mutagen-induced DNA damage and repair in protoplasts of Aspergillus
      nidulans. The assay shows a reduced rate of repair of DNA damage in methionine
      and arginine auxotrophs (methG and argB), which were shown previously to be
      hypersensitive to UV radiation and chemical mutagens. The assay also showed a
      considerably reduced ability to repair mutagen-induced damage in the uv-sensitive
      mutants uvsB and uvsH. The increased sensitivity of amino acids auxotrophs to
      mutagens is, therefore, correlated with a reduced capacity to repair mutagen
      induced DNA damage.

PMID- 8543033
TI  - Molecular cloning and functional expression of a recombinant 72.5 kDa fragment of
      the 110 kDa regulatory subunit of smooth muscle protein phosphatase 1M.
AB  - We have cloned a partial rat kidney cDNA that encodes a 72.5 kDa N terminal
      fragment of a third isoform of the M110 subunit of phosphatase 1. This new
      isoform contains an insert in the 542-597 position not present in the M110
      previously cloned (Chen et al. (1994) FEBS Lett. 356, 51-55) from the same
      species. The encoded cDNA was expressed as a soluble GST-fusion protein in E.
      coli, and its ability to interact with native PP-1C was measured both in vitro
      and in permeabilized smooth muscle. In vitro, the fusion protein was capable of
      selectively binding PP-1C and increasing the substrate specificity of the
      phosphatase towards myosin 13.2 +/- 3.5-fold (S.E. of the mean, n = 3). In
      permeabilized smooth muscle pretreated with microcystin, the recombinant protein
      alone (1.0 microM) did not cause relaxation, but did significantly enhance the
      ability of PP-1C (0.3 microM) to relax the muscle. These findings show that the N
      terminal domain of the M110 subunit is the primary site for both PP-1C and myosin
      binding, and thereby determines myosin specificity. The presence of isoformic
      variation within this sequence may permit organ/cell specific regulation of
      phosphorylation sites.

PMID- 8543034
TI  - Protein O-glycosylation in Saccharomyces cerevisiae: the protein O
      mannosyltransferases Pmt1p and Pmt2p function as heterodimer.
AB  - The protein O-mannosyltransferases Pmt1p and Pmt2p are catalyzing the O
      glycosylation of serine and threonine residues in the endoplasmic reticulum of
      yeast. Deletion of each of these proteins by disruption of the corresponding gene
      leads to a dramatic decrease of mannosyltransferase activity in vitro. With an
      anti-Pmt1p immunoaffinity column a complex of Pmt1p and a second protein was
      purified; this protein turned out to be Pmt2p. Overexpression of Pmt1p or Pmt2p,
      respectively, does not increase mannosyltransferase activity in vitro.
      Overexpression of both mannosyltransferases together, however, raises in vitro
      activity threefold. These data indicate that Pmt1p and Pmt2p function as a
      complex catalyzing protein O-glycosylation in yeast.

PMID- 8543035
TI  - Reconstitution of skinned cardiac fibres with human recombinant cardiac troponin
      I mutants and troponin-C.
AB  - Troponin C (TnC) could be extracted from skinned porcine cardiac muscle fibres
      and their Ca2+ sensitivity restored by reconstitution with recombinant human
      cardiac TnC. After extraction of troponin I (TnI) and TnC using the vanadate
      treatment method of Strauss et al. [Strauss, J. D., Zeugner, C., Van Eyk, J.E.,
      Bletz, C., Troschka, M. and Ruegg, J.C. (1992) FEBS Lett. 310, 229-234], skinned
      porcine cardiac muscle fibres were reconstituted with wild-type recombinant human
      cardiac TnC and either wild-type cardiac TnI or several mutant isoforms of human
      TnI. Reconstitution with wild-type proteins restored the Ca2+ sensitivity of the
      tissue and phosphorylation of the TnI with the catalytic subunit of protein
      kinase A reduced the Ca2+ sensitivity (i.e.-log[Ca2+] for 50% of maximal force)
      as has been shown by others. However, reconstitution with the TnI mutant Ser
      23Asp/Ser-24Asp mimicking the phosphorylated form of cardiac TnI, led to a
      reduced Ca2+ sensitivity compared with reconstitution with wild-type TnI, whereas
      the mutant Ser-23Ala/Ser-24Ala behaved as the dephosphorylated form of TnI. These
      data confirm the importance of negative charge in this region of the TnI molecule
      in altering the Ca2+ responsiveness in this system.

PMID- 8543036
TI  - Thermal stabilization of a single-chain Fv antibody fragment by introduction of a
      disulphide bond.
AB  - A disulphide bond was introduced into a single-chain Fv form of the
      anticarbohydrate antibody, Se155-4 by replacing Ala-L57 of the light chain and
      Asp-H106 of the heavy chain with cysteines, by site-directed mutagenesis. To
      maintain the salt-bridge from the latter residue to Arg-H98, Tyr-107 was also
      altered to Asp. The resulting ds-scFv was shown to retain full antigen-binding
      activity, by enzyme immunoassay and surface plasmon resonance analysis of binding
      kinetics. Compared with the parent scFv, the disulphide bonded form was shown to
      have enhanced thermal stability, by Fourier transform IR spectroscopy. The Tm was
      raised from 60 degrees C to 69 degrees C. The ds-scFv form thus combines the
      stable monomeric form of the disulphide form with the expression advantages of
      the scFv.

PMID- 8543037
TI  - The human beta 2-adrenergic receptor expressed in Schizosaccharomyces pombe
      retains its pharmacological properties.
AB  - We have developed a rapid and efficient expression system to study the human beta
      2 adrenergic receptor (hu beta 2AR) in the fission yeast Schizosaccharomyces
      pombe. This was achieved by cloning the hu beta 2AR gene, modified by replacement
      of the 5' untranslated and a small part of the N-terminal coding sequence (first
      14 amino acids) with the corresponding region of the yeast Saccharomyces
      cerevisiae STE2 (alpha-factor receptor) gene. The gene was then placed under the
      control of a S. pombe constitutive promoter for alcohol dehydrogenase (adh). Hu
      beta 2AR expression was assessed by immunoblot analysis of the chimeric protein
      with an anti-STE2 serum raised against a dodecapeptide homologous to the N
      terminal amino acids of STE2 and ligand binding was assayed using
      [125I]cyanopindolol. We demonstrate here that the chimeric receptor expressed in
      S. pombe exhibits the same characteristic ligand specificity and affinity as that
      of the authentic hu beta 2AR. This system constitutes a convenient alternative to
      existing methods for studying seven transmembrane domain receptors due to its
      simplicity and high reproducibility.

PMID- 8543038
TI  - A reinvestigation of the covalent structure of Pseudomonas aeruginosa cytochrome
      c peroxidase.
AB  - The amino acid sequence of cytochrome c peroxidase from Pseudomonas aeruginosa
      has been determined using classical chemical degradation techniques combined with
      accurate mass analysis of all the generated peptides. The sequence obtained is
      composed of 346 amino acids and confirms the recently published cDNA-derived
      sequence except at one position [Ridout et al. (1995) FEBS Lett. 365, 152-154].
      Based on this sequence, we propose a new model for the binding of the peroxide
      and the cytochrome electron donor to CCP which is in essence the reverse of the
      one proposed by Ellfolk et al.

PMID- 8543039
TI  - Crystal structure of an uncleaved alpha 1-antitrypsin reveals the conformation of
      its inhibitory reactive loop.
AB  - The crystal structure of a recombinant human alpha 1-antitrypsin, in the
      uncleaved and uncomplexed state, has been determined by X-ray crystallographic
      methods and refined to an R-factor of 18.4% for 8.0-3.46 A data with good
      stereochemistry. This structure provides the first view at the inhibitory loop
      and the central beta-sheet A of the uncleaved alpha 1-antitrypsin. The reactive
      loop takes a distorted helical conformation and no pre-insertion of two residues
      in the reactive loop into the beta-sheet A is observed. The present structure is
      largely in agreement with the model predicted by Engh, Wright, and Huber [Prot.
      Eng. 3 (1990) 469-477].

PMID- 8543040
TI  - Precise mapping of the tms1 binding site on p53.
AB  - Originally identified as multicopy suppressor of a lethal growth arrest caused by
      expression of a tumour mutant cDNA of p53 in fission yeast the tms1 gene product
      was found to form stable complexes with p53 in yeast. By using purified
      recombinant proteins multimeric complexes of tms1 and p53 could be demonstrated
      and recently the p53 binding site on the tms1 protein was established to the
      sequence YYITTEDFCT (aa 116-125) in the vicinity of a well conserved cell
      division motif. Here we report the precise mapping of the tms1 binding site on
      the p53 protein to the sequence LQIRGRERFE (aa 330-339) which defines a new
      functional domain on the p53 protein.

PMID- 8543041
TI  - The beta 1-subunit is essential for modulation by protein kinase C of an human
      and a non-human L-type Ca2+ channel.
AB  - We have investigated in Xenopus oocytes the effects of phorbol ester-induced
      protein kinase C (PKC) stimulation on dihydropyridine (DHP)-insensitive and 
      sensitive Ca2+ channels. DHP-insensitive Ba2+ currents (IBa) were recorded from
      endogenous channels in non-injected oocytes and in oocytes injected with cRNAs
      encoding the auxiliary rabbit alpha 2/delta and beta 1 Ca2+ channel subunits. A
      human alpha 1C cRNA, injected alone or in combination with cRNAs of the auxiliary
      subunits, was used for studying DHP-sensitive IBa. We found that DHP-insensitive
      IBa was increased by 4 beta-phorbol 12-myristate 13-acetate (PMA), while DHP
      sensitive IBa was decreased. In both cases, the effects depended only on the co
      expression of the beta 1 subunit.

PMID- 8543042
TI  - Isolation of CF0CF1 from Chlamydomonas reinhardtii cw15 and the N-terminal amino
      acid sequences of the CF0CF1 subunits.
AB  - CF0CF1 was isolated from chloroplasts of the cell wall-deficient Chlamydomonas
      reinhardtii strain cw15. The subunit pattern was analyzed by SDS-gel
      electrophoresis and the N-terminal amino acid sequences of all nine subunits were
      determined by microsequencing. The amino acid sequences of subunits alpha, beta,
      gamma and epsilon match with those derived from the corresponding Chlamydomonas
      DNA sequences. In variance with the previously assumed N-terminus of beta;
      however, it was found that the first 11 amino acids are lacking. The subunits
      delta, I, II, III and IV were identified by comparison with known sequences of
      homologous polypeptides of higher plant chloroplasts and cyanobacteria,
      respectively.

PMID- 8543043
TI  - Rapid purification of a functionally active plant sucrose carrier from transgenic
      yeast using a bacterial biotin acceptor domain.
AB  - A rapid and efficient method has been used for the purification of a Plantago
      major sucrose carrier from Saccharomyces cerevisiae. The C-terminal fusion of a
      bacterial biotin acceptor domain to the carrier protein did not interfere with
      the targeting to the yeast plasma membrane nor with the catalytic activity of the
      sucrose carrier. The chimeric construct is biotinylated by yeast cells in vivo
      and represents the only biotinylated protein in yeast membranes. Solubilized
      biotinylated carrier protein binds selectively to immobilized monomeric avidin
      and can be eluted as pure protein with free biotin. The purified protein is
      functionally active and catalyzes the energy-dependent transport of sucrose into
      proteoliposomes.

PMID- 8543044
TI  - Synthesis, cloning and expression in Escherichia coli of a gene coding for the
      Met8-->Leu CMTI I--a representative of the squash inhibitors of serine
      proteinases.
AB  - A chemically synthesized gene coding for a Cucurbita maxima trypsin inhibitor
      modified at position P'3 (Met8-->Leu CMTI I), i.e. at the third position
      downstream of the reactive site bond (Arg5-Ile), was cloned into a derivative of
      the plasmid pAED4 that utilizes a T7 expression system. The gene was expressed in
      Escherichia coli as a fusion protein that accumulates in inclusion bodies. After
      reduction and CNBr cleavage of the fusion protein followed by oxidative refolding
      and reverse-phase HPLC, about 5 mg of pure protein was obtained per 1 of cell
      culture. Association constants of recombinant Leu-8-CMTI I with bovine beta
      trypsin and human cathepsin G are the same, within experimental error, as for
      CMTI I isolated from a natural source.

PMID- 8543045
TI  - Evidence against specific binding of salicylic acid to plant catalase.
AB  - It was demonstrated that salicylic acid (SA) not only binds to catalase from
      differentiated higher plants and plant cell suspension cultures but also to those
      of fungi and animals. SA bound specifically to iron-containing enzymes, such as
      catalase, aconitase, lipoxidase and peroxidase, while not to iron-free plant
      enzymes. On the grounds of these experiments, the claim is further challenged
      that SA is a signalling compound and second messenger in plants that activates
      plant defense-related genes through elevated H2O2 levels by specifically
      inhibiting catalase activity. SA may just function as a phytoalexin.

PMID- 8543046
TI  - Arginine-427 in the Na+/glucose cotransporter (SGLT1) is involved in trafficking
      to the plasma membrane.
AB  - To investigate the role of charged intramembrane residues in the function of the
      rabbit Na+/glucose cotransporter (rbSGLT1) we substituted arginine-427 (R427) by
      alanine in the putative domain M9 SGLT1. This residue is conserved in all the
      members of the SGLT1 family. The mutant protein (R427A) was expressed in Xenopus
      oocytes and, although Western blot analysis revealed that it was produced in
      amounts comparable to wild-type, no function was measured. Freeze-fracture
      analysis showed that R427A SGLT1 was not in the plasma membrane while
      immunocytochemical experiments localized the transporter to just beneath it.
      These results indicate that arginine-427 plays a critical role in SGLT1
      trafficking to the plasma membrane.

PMID- 8543047
TI  - Low temperature persistence of type I antifreeze protein is mediated by cold
      specific mRNA stability.
AB  - In winter flounder, the levels of type I antifreeze protein (AFP) and its mRNA
      vary seasonally by as much as 1000-fold. Elevated levels in the fall are prompted
      by the loss of long day-lengths, while higher spring temperatures correlate with
      AFP clearance. We have investigated the role of temperature on AFP accumulation
      using transgenic Drosophila melanogaster by expressing multiple AFP genes under
      control of the heat-inducible hsp70 promoter. AFP and AFP mRNA persisted far
      longer in flies reared at 10 degrees C compared to 22 degrees C. This difference
      appears to be mediated by cold-specific mRNA stability since no such temperature
      effect was observed with either an endogenous heat-inducible mRNA or a
      constitutively expressed mRNA.

PMID- 8543048
TI  - Immunological evidence that HMG-CoA reductase kinase-A is the cauliflower
      homologue of the RKIN1 subfamily of plant protein kinases.
AB  - Three different antibodies against the RKIN1 and BKIN12 gene products from rye
      and barley recognized the 58 kDa subunit of HMG-CoA reductase kinase-A (HRK-A)
      from Brassica oleracea on Western blots. HRK-A was also detected by an
      antipeptide antibody in enzyme-linked immunoassays, and this was competed by the
      peptide antigen. HRK-A was not recognized by antibodies against plant, mammalian
      and Saccharomyces cerevisiae relatives of RKIN1, i.e. wheat PKABA1, rat AMP
      activated protein kinase and S. cerevisiae Snf1p. RKIN1/HMG-CoA reductase kinase
      A are now among the first protein kinases in plants to be well characterized at
      both the molecular and biochemical levels.

PMID- 8543049
TI  - Characterization of functionally independent domains in the human ubiquitin
      conjugating enzyme UbcH2.
AB  - UbcH2 encodes a human ubiquitin conjugating enzyme (E2) able to conjugate
      ubiquitin to histone H2A in an E3 independent manner in vitro, which indicates
      that UbcH2 directly interacts with its substrates. To identify parts of the
      enzyme that are capable of binding H2A, we expressed several deletion mutants of
      UbcH2 in E. coli and tested the ability of the affinity purified mutant proteins
      to ubiquitinate H2A in the presence of bacterial expressed E1 and ubiquitin. With
      this in vitro assay we identified a C-terminal part of UbcH2 to be important for
      the interaction with H2A. Transfer of this C-terminal domain to another human E2,
      which is unable to catalyze ubiquitination of histones, leads to a fully active
      hybrid human ubiquitin conjugating enzyme capable of H2A ubiquitination. These
      results demonstrate that UbcH2 consists of two functionally independent domains.
      A N-terminal core domain with ubiquitin conjugating activity, and a C-terminal
      domain which interacts with substrate proteins.

PMID- 8543050
TI  - A mutation affecting carbon catabolite repression suppresses growth defects in
      pyruvate carboxylase mutants from Saccharomyces cerevisiae.
AB  - Yeasts with disruptions in the genes PYC1 and PYC2 encoding the isoenzymes of
      pyruvate carboxylase cannot grow in a glucose-ammonium medium (Stucka et al.
      (1991) Mol. Gen. Genet. 229, 307-315). We have isolated a dominant mutation, BPC1
      1, that allows growth in this medium of yeasts with interrupted PYC1 and PYC2
      genes. The BPC1-1 mutation abolishes catabolite repression of a series of genes
      and allows expression of the enzymes of the glyoxylate cycle during growth in
      glucose. A functional glyoxylate cycle is necessary for suppression as a
      disruption of gene ICL1 encoding isocitrate lyase abolished the phenotypic effect
      of BPC1-1 on growth in glucose-ammonium. Concurrent expression from constitutive
      promoters of genes ICL1 and MLS1 (encoding malate synthase) also suppressed the
      growth phenotype of pyc1 pyc2 mutants. The mutation BPC1-1 is either allelic or
      closely linked to the mutation DGT1-1.

PMID- 8543051
TI  - The pharmacological profile of the vesicular monoamine transporter resembles that
      of multidrug transporters.
AB  - Vesicular neurotransmitter transporters function in synaptic vesicles and other
      subcellular organelles and they were thought to be involved only in
      neurotransmitter storage. Several findings have led us to test novel aspects of
      their function. Cells expressing a c-DNA coding for one of the rat monoamine
      transporters (VMAT1) become resistant to the neurotoxin N-methyl-4
      phenylpyridinium (MPP+) [Liu et al. (1992) Cell, 70, 539-551]. The basis of the
      resistance is the VMAT1-mediated transport and sequestration of the toxin into
      subcellular compartments. In addition, the deduced sequence of VMAT1 predicts a
      protein that shows a distinct homology to a class of bacterial drug resistance
      transporters (TEXANs) that share some substrates with mammalian multidrug
      resistance transporters (MDR) such as the P-glycoprotein. These findings induced
      us to test whether compounds that are typically transported by MDR interact also
      with vesicular transporters. The use of [3H]reserpine binding to determine drug
      interactions with VMAT allowed assessment of the ability of various drugs to bind
      to the substrate site of the transporter. Cytotoxic compounds such as ethidium,
      isometamidium, tetraphenylphosphonium, rhodamine, tacrine and doxorubicin,
      interact specifically with vesicular monoamine transporters. Verapamil, a calcium
      channel blocker, is also a competitive inhibitor of transport. In the case of
      rhodamine, fluorescence measurements in digitonin-permeabilized cells
      demonstrated ATP-dependent VMAT-mediated transport. The results imply that even
      though the bacterial and vesicular transporters are structurally different from
      the P-glycoprotein, they share a similar substrate range. These findings suggest
      a novel possible way of protection from the effects of toxic compounds by removal
      to subcellular compartments.

PMID- 8543052
TI  - Time-resolved solid-state REDOR NMR studies of UDP N-acetylglucosamine
      enolpyruvyl transferase.
AB  - The new method of time-resolved solid-state rotational echo double resonance
      (REDOR) NMR spectroscopy introduced recently by this laboratory has been applied
      to the enzyme uridine N-acetylglucosamine (UDP-NAG) enolpyruvyl transferase
      (EPT), with the goal of probing the interactions between reactive species and
      their enzyme active site. The approach has been used in a qualitative fashion
      with the enzyme-inhibitor and enzyme-intermediate complexes of uniformly 15N
      labeled UDP-NAG EPT, trapped under steady-state and pre-steady-state conditions.
      A different set of intermolecular interactions between the substrates UDP-NAG,
      UDP-NAG plus 3-Z-fluorophosphoenolpyruvate, covalent O-phosphothioketal, and UDP
      NAG plus phosphoenolpyruvate trapped under time-resolved conditions (after 50 ms
      reaction time), and the EPT enzyme active site were observed, and this is
      contrasted to a similar study of the interactions in a related enzyme, 5
      enolpyruvyl-shikimate-3-phosphate synthase.

PMID- 8543053
TI  - Ketoconazole and other imidazole derivatives are potent inhibitors of peroxisomal
      phytanic acid alpha-oxidation.
AB  - The imidazole antimycotics like ketoconazole, clotrimazole, bifonazole,
      miconazole and CO, known as powerful inhibitors of cytochrome P-450, are potent
      inhibitors of peroxisomal phytanic acid alpha-oxidation to pristanic acid
      suggesting the possible involvement of the cytochrome P-450 mono-oxygenase system
      in this oxidation. In contrast to the inhibition of the oxidation of [1
      14C]phytanic acid, [1-14C]phytanoyl-CoA and [(2,3)-3H]phytanic acid, these drugs
      and CO have no effect on the oxidation of [1-14C]alpha-hydroxy phytanic acid
      indicating that these drugs and CO inhibit only the alpha-hydroxylation of
      phytanic acid. These studies using purified peroxisomes from liver and cultured
      human skin fibroblasts and Hep G2 cells clearly demonstrate that alpha
      hydroxylation, an intermediate step in the alpha-oxidation of phytanic acid found
      to be impaired in Refsum Disease, is mediated by cytochrome P-450 containing
      enzyme.

PMID- 8543054
TI  - Purification and reconstitution of activity of Saccharomyces cerevisiae P450 61,
      a sterol delta 22-desaturase.
AB  - P450 was purified from microsomal fractions of a strain of Saccharomyces
      cerevisiae which contained detectable P450 despite the disruption of CYP51A1. The
      P450 had a molecular mass of 58 kDa, similar to P450 51A1, and in a reconstituted
      assay with rabbit NADPH-P450 reductase and dilauryl phosphotidylcholine exhibited
      activity for conversion of ergosta-5,7-dienol into ergosterol. N-Terminal amino
      acid sequencing of the purified protein corresponded to the translated sequence
      of P450 61 which was recently identified during sequencing of chromosome XIII.
      This allowed the function of this family of P450 to be identified as sterol delta
      22-desaturation in the pathway of ergosterol biosynthesis.

PMID- 8543055
TI  - A novel approach for expression cloning of small GTPases: identification, tissue
      distribution and chromosome mapping of the human homolog of rheb.
AB  - We report a novel approach for identifying monomeric GTP-binding proteins that is
      based on probing cDNA expression libraries with [alpha-32P]GTP. In short, a
      nitrocellulose replica from a plated cDNA expression library is treated with 2%
      SDS to block the GTP-binding activity of various G proteins expressed by E. coli,
      thus allowing the direct identification of positive clones. Using this procedure
      we have cloned several small GTP-binding proteins from human keratinocytes
      including the human homolog of rheb, a novel member of the ras-related GTP
      binding proteins. Human rheb cDNA shares 90% identity with the rat counterpart
      and it is highly upregulated in transformed human cells of various origin.
      Northern analysis showed that human rheb is ubiquitously expressed, with the
      highest levels observed in skeletal and cardiac muscle, and not in brain, as it
      is the case for rat rheb. The human RHEB gene was mapped to chromosome 10q11.

PMID- 8543056
TI  - Co-selection of cognate antibody-antigen pairs by selectively-infective phages.
AB  - We have developed a chloramphenicol resistant derivative of fd phage with which
      cognate pairs of antibodies and antigens can be selected. The phage genome
      encodes a fusion of single-chain antibody to the C-terminal domain of gIIIp,
      rendering the phage non-infective. The antigen fused to the N-terminal domains of
      gIIIp is encoded in the same phage genome. Antigen and antibody fusion interact
      with each other in the periplasm of the phage-producing cell, restoring
      infectivity. This system has a very low background and will allow simultaneous
      randomisation of antibody and antigen.

PMID- 8543057
TI  - Phylogenetic classification of the major superfamily of membrane transport
      facilitators, as deduced from yeast genome sequencing.
AB  - From the approximately 5000 open reading frames presently identified by
      systematic sequencing of the yeast genome, 100 Saccharomyces cerevisiae transport
      proteins belonging to the major facilitator superfamily (MFS), were assigned to
      17 families on the basis of extensive database searches and binary comparisons.
      These families include multidrug resistance proteins and transport proteins for
      sugars, amino acids, uracil/allantoin, allantoate, phosphate, purine/cytosine,
      proteins, peptides, potassium, sulfate, and urea. Four new families of unknown
      function have been identified. For the sugar and amino acid transport proteins,
      alignments were made and phylogenetic trees were constructed allowing the
      identification of several clusters of proteins presumably exhibiting similar
      transport functions.

PMID- 8543058
TI  - TNF-alpha inhibits glucose-induced insulin secretion in a pancreatic beta-cell
      line (INS-1).
AB  - Recent studies suggest that TNF-alpha affects various biochemical and
      physiological processes which may be linked to the etiology of non-insulin
      dependent diabetes mellitus (NIDDM). For example, TNF-alpha interferes with the
      signaling of the insulin receptor and the metabolism of glucose transporters. The
      possibility that TNF-alpha might directly reduce glucose-stimulated insulin
      secretion in pancreatic beta-cells was examined by using an established
      pancreatic beta-cell line (INS-1). TNF-alpha did not affect glucose-induced acute
      insulin secretion (30 min). However, over a longer time period (24 h), TNF-alpha
      decreased glucose-induced insulin secretion without affecting the total amount of
      insulin in the cell. In the presence of TNF-alpha levels of 0, 10, 100 and 1000
      U/ml, the respective 20 mM glucose-induced insulin secretion was 1.736 +/- 0.166,
      1.750 +/- 0.302, 1.550 +/- 0.200, and 1.400 +/- 0.112 mU/ml per 3 x 10(5) cells
      in 24 h.

PMID- 8543059
TI  - The effect of heparin on Cu(2+)-mediated oxidation of human low-density
      lipoproteins.
AB  - The effect of heparin (HE) on the susceptibility of human low-density lipoprotein
      (LDL) to Cu(2+)-induced oxidation was investigated by monitoring conjugated diene
      formation. HE did not modify the maximum formation of conjugated diene, but
      increased markedly the lag phase. The plot of change in oxidation rate vs. time
      showed that the absolute value of Vmax was dependent on Cu2+ concentration and
      that HE increased the time necessary to reach Vmax. The value of constant K (the
      Cu2+ concentration producing a tlag of twice the minimum value) increased in the
      presence of HE, whereas the value of tmin (the time theoretically required for
      LDL oxidation at an infinite Cu2+ concentration) was not substantially affected.
      These results indicate that HE might play a protective antioxidant effect on LDL,
      probably affecting both the structural properties of the particle and the amount
      of Cu2+ available for the oxidation.

PMID- 8543060
TI  - A novel partner for the GTP-bound forms of rho and rac.
AB  - Using the yeast two hybrid system and overlay assays we identified a putative
      rholrac effector, citron, which interacts with the GTP-bound forms of rho and
      rac1, but not with cdc42. Extensive homologies to known proteins were not
      observed. This 183 kDa protein contains a C6H2 zinc finger, a PH domain, and a
      long coiled-coil forming region including 4 leucine zippers and the rholrac
      binding site. We recently identified three others putative rho effectors
      characterized by a common rho binding motif. Citron does not share this motif and
      displays a distinctive protein organization, thus defining a separate class of
      rho partners.

PMID- 8543061
TI  - Human ClpP protease: cDNA sequence, tissue-specific expression and chromosomal
      assignment of the gene.
AB  - We identified three overlapping human expressed sequence tags with significant
      homology to the E. coli ClpP amino sequence by screening the EMBL nucleotide
      database. With this sequence information we applied 5' and 3'-rapid amplification
      of cDNA ends (RACE) to amplify and sequence human clpP cDNA in two overlapping
      fragments. The open reading frame encodes a 277 amino acid long precursor
      polypeptide. Two ClpP specific motifs surrounding the active site residues are
      present and extensive homology to ClpP's from other organisms was observed.
      Northern blotting showed high relative expression levels of clpP mRNA in skeletal
      muscle, intermediate levels in heart, liver and pancreas, and low levels in
      brain, placenta, lung and kidney. By analysis of human/rodent cell hybrids the
      human clpP gene was assigned to chromosome 19.

PMID- 8543062
TI  - Site-directed mutagenesis of Thermus thermophilus EF-Tu: the substitution of
      threonine-62 by serine or alanine.
AB  - The invariant threonine-62, which occurs in the effector region of all GTP/GDP
      binding regulatory proteins, was substituted via site-directed mutagenesis by
      alanine and serine in the elongation factor Tu from Thermus thermophilus. The
      altered proteins were overproduced in Escherichia coli, purified and
      characterized. The EF-Tu T62S variant had similar properties with respect to
      thermostability, aminoacyl-tRNA binding, GTPase activity and in vitro translation
      as the wild-type EF-Tu. In contrast, EF-Tu T62A is severely impaired in its
      ability to sustain polypeptide synthesis and has only very low intrinsic and
      ribosome-induced GTPase activity. The affinity of aminoacyl-tRNA to the EF-Tu
      T62A.GTP complex is almost 40 times lower as compared to the native EF-Tu.GTP.
      These observations are in agreement with the tertiary structure of EF-Tu.GTP, in
      which threonine-62 is interacting with the Mg2+ ion, gamma-phosphate of GTP and a
      water molecule, which is presumably involved in the GTP hydrolysis.

PMID- 8543063
TI  - Identification of the nicking tyrosine of geminivirus Rep protein.
AB  - The replication initiator (Rep) proteins of geminiviruses perform a DNA cleavage
      and strand transfer reaction at the viral origin of replication. As a reaction
      intermediate, Rep proteins become covalently linked to the 5' end of the cleaved
      DNA. We have used tomato yellow leaf curl virus Rep protein for in vivo and in
      vitro analyses. Isolating a covalent peptide-nucleotide complex, we have
      identified the amino acid of Rep which mediates cleavage and links the protein to
      DNA. We show that tyrosine-103, located in a conserved sequence motif, initiates
      DNA cleavage and is the physical link between geminivirus Rep protein and its
      origin DNA.

PMID- 8543064
TI  - Functional expression of bacteriorhodopsin in oocytes allows direct measurement
      of voltage dependence of light induced H+ pumping.
AB  - We report on the first successful expression of the light driven H+ pump,
      bacteriorhodopsin, into the plasma membrane of oocytes from Xenopus laevis. The
      light induced photocurrents which reflect the pumping of H+ by BR were analysed
      under voltage clamp conditions. At least 100 active BR molecules per microns 2
      were expressed in the plasma membrane so that both the voltage clamp and giant
      patch clamp method could be applied. We show that H+ pumping by BR is modulated
      by the membrane potential, i.e. the pump current shows strong voltage dependence
      in the range measured between -165 mV to +60 mV.

PMID- 8543066
TI  - Phospholipid-synthesizing enzymes in Golgi membranes of the yeast, Saccharomyces
      cerevisiae.
AB  - Golgi membranes of the yeast, Saccharomyces cerevisiae, were isolated by a method
      similar to the procedure described by Cleves et al. [Cell 64 (1991) 789-800].
      Marker proteins of the Golgi, such as Kex2 protease and GDPase, are highly
      enriched in these preparations. The phospholipid and ergosterol content of Golgi
      membranes is low. Phosphatidylcholine, phosphatidylethanolamine, and
      phosphatidylinositol are the major phospholipids of this compartment. The amount
      of phosphatidylserine in the Golgi is significantly higher than in yeast bulk
      membranes. Inositol-containing sphingolipids, especially
      inositolphosphorylceramide, are highly enriched in Golgi membranes. Two
      phospholipid-synthesizing enzymes, namely phosphatidylinositol synthase and sn
      1,2-diacylglycerol cholinephosphotransferase, are detected in the Golgi at a
      specific activity which exceeds that of the endoplasmic reticulum.

PMID- 8543065
TI  - Gelatinase A possesses a beta-secretase-like activity in cleaving the amyloid
      protein precursor of Alzheimer's disease.
AB  - The ability of the 72 kDa gelatinase A to cleave the amyloid protein precursor
      (APP) was investigated. HeLa cells were transfected with an APP695 plasmid. The
      cells were incubated with gelatinase A, which cleaved the 110 kDa cell-surface
      APP, releasing a 100 kDa form of the protein. A peptide homologous to the beta
      secretase site was cleaved by gelatinase A adjacent to a glutamate residue at
      position -3 (beta A4 numbering system). A peptide homologous to the alpha
      secretase site was not cleaved. The results demonstrate that 72 kDa gelatinase A
      is not an alpha-secretase, but that it may have a beta-secretase activity.

PMID- 8543067
TI  - Constitutive activity of the M1-M4 subtypes of muscarinic receptors in
      transfected CHO cells and of muscarinic receptors in the heart cells revealed by
      negative antagonists.
AB  - We investigated whether muscarinic receptors of the M1-M4 receptor subtypes are
      constitutively active. We have found that the synthesis of cyclic AMP was
      enhanced by the muscarinic antagonists atropine and N-methylscopolamine (NMS) in
      Chinese hamster ovary (CHO) cells stably transfected with human m2 and m4
      muscarinic receptor genes and in rat cardiomyocytes expressing the M2 receptor
      subtype, and that the production of inositol phosphates was inhibited by atropine
      and NMS in CHO cells stably transfected with human m1 and m3 and with rat m1
      muscarinic receptor genes. The muscarinic antagonists quinuclidinyl benzilate and
      AF-DX 116 had no effect in some cases and acted like atropine and NMS in others.
      We conclude that the M1-M4 subtypes of muscarinic receptors are constitutively
      active in the CHO cell lines expressing them and in cardiomyocytes and that
      atropine and NMS act as negative antagonists on these receptor subtypes by
      stabilizing them in the inactive conformation.

PMID- 8543068
TI  - Phylogenetic, structural and functional analyses of the LacI-GalR family of
      bacterial transcription factors.
AB  - Phylogenetic tree construction for 25 sequenced members of the LacI-GalR family
      (LGF) of transcription factors revealed that almost all branches are similar in
      length, radiating essentially from a single point. This observation suggests that
      most of these proteins arose by duplication events which occurred at a specific
      time in evolutionary history, and that further duplication events were rare.
      Analyses of the multiple alignment of the LGF proteins lead to suggestions
      regarding structure-function relationships and reveal that the helix-turn-helix
      DNA-binding motif of LGF proteins is similar in sequence to those of numerous non
      homologous DNA-binding proteins.

PMID- 8543069
TI  - Childhood blindness in India.

PMID- 8543070
TI  - Childhood blindness in India: causes in 1318 blind school students in nine
      states.
AB  - It is estimated that at least 200,000 children in India have severe visual
      impairment or blindness and approximately 15,000 are in schools for the blind.
      Although this represents a small percentage of the estimated 5 million blind in
      India, it is significant in terms of 'blind-years'. Strategies to combat
      childhood blindness require accurate data on the causes to allocate resources to
      appropriate preventive and curative services. Since socio-economic factors vary
      in different areas of this industrializing country data should be representative
      of the country as a whole. This is the first multi-state study to be undertaken
      in India using the Record for Children with Blindness and Low Vision from the
      World Health Organization/PBL Programme. A total of 1411 children in 22 schools
      from nine states in different geographical zones were examined by an
      ophthalmologist and optometrist. Of these, 1318 children were severely visually
      impaired or blind (SVI/BL). The major causes of SVI/BL in this study were: (1)
      corneal staphyloma, scar and phthisis bulbi (mainly attributable to vitamin A
      deficiency) in 26.4%; (2) microphthalmos, anophthalmos and coloboma in 20.7%; (3)
      retinal dystrophies and albinism in 19.3%; and (4) cataract, uncorrected aphakia
      and amblyopia in 12.3%. This mixed pattern of causes lies in an intermediate
      position between the patterns seen in developing countries and those seen in
      industrialised countries. The causes identified indicate the importance both of
      preventive public health strategies and of specialist paediatric ophthalmic and
      optical services in the management of childhood blindness in India.

PMID- 8543071
TI  - Longitudinal change of refractive error in infants during the first year of life.
AB  - Using cycloplegia, the change in ametropia of 113 infants was followed at 3 month
      intervals over the first year of life. Scatterplots of the spherical equivalent
      power show that the dioptric differences exhibit a significant myopic shift of 
      0.38 ds between 26 and 36 weeks and -0.38 ds between 36 and 52 weeks. The spread
      of the dioptric differences (95% CI) does not appear to be related to the
      magnitude of the ametropia present and decreases with time. By 12 months of age
      the frequency distribution of the spherical equivalent appears to become
      leptokurtic as it is in the adult. On average the astigmatism was of low degree
      (less than 1 dioptre cylinder) and with the rule. Anisometropia was rarely seen.
      The results of this longitudinal study point to an optimal time for screening and
      perhaps prescribing for 'abnormal' refractive error between 9 and 12 months of
      age.

PMID- 8543072
TI  - Management of strabismus due to orbital myositis.
AB  - We report on 5 consecutive patients seen at the botulinum toxin clinic at
      Moorfields Eye Hospital with an ocular motility disorder secondary to orbital
      myositis. CT scans demonstrated involvement of one or both of the medial recti in
      the inflammatory process in all 5 patients. In addition 1 patient had involvement
      of both the lateral recti and the right superior rectus. Two patients had been
      treated with oral steroids, 3 with non-steroidal anti-inflammatory agents, and 1
      with orbital radiotherapy. Prior to toxin injection 3 patients had an esotropia
      (ranging from 4 delta to 30 delta) and two an exotropia (52 delta and 85 delta).
      A vertical imbalance was present in 3, and all 5 patients had symptomatic
      diplopia. A total of six injections were given to 5 patients, 2 of whom later
      went on to have surgery. Toxin injection reduced the angle of the deviation to
      less than 10 delta in 4 patients, all of whom are now asymptomatic. The fifth
      patient has persistent diplopia despite two operations to correct a large
      exotropia. We discuss the role of botulinum toxin and surgery in the management
      of strabismus due to orbital myositis.

PMID- 8543073
TI  - Prevention of immune-mediated corneal graft destruction with the anti-lymphocyte
      monoclonal antibody, CAMPATH-1H.
AB  - We report a patient with peripheral rheumatoid corneal melting who developed a
      corneal perforation in one eye requiring tectonic keratoplasty. Nine consecutive
      corneal grafts were rapidly destroyed despite systemic immunosuppression with
      corticosteroid, cyclophosphamide, azathioprine and cyclosporin A. A rejection
      episode was observed in one graft before it melted and allograft rejection may
      have contributed to the destruction of other grafts. Corneal graft survival was
      ultimately achieved by systemic immunosuppression with the anti-lymphocyte
      monoclonal antibody, CAMPATH-1H. A single episode of rejection developed in the
      early post-operative period which was easily reversed by topical corticosteroid.
      Corneal melting has not recurred and the graft has now remained intact and clear
      for 24 months. Anti-lymphocyte monoclonal antibodies may therefore provide
      effective immunosuppression in the treatment of refractory ocular disorders.

PMID- 8543074
TI  - Severe idiopathic posterior scleritis in children.
AB  - Posterior scleritis is an uncommon condition that usually occurs in adults and
      the diagnosis is often missed. It is even more rare in children. We report five
      cases of the disease in children. The patients presented with severe pain in an
      inflamed eye and usually had orbital signs with lid swelling and limitation of
      extraocular movements; four of the five had optic disc swelling and two had
      exudative retinal detachments. The diagnosis was confirmed on B-scan
      ultrasonography and CT scanning and no child had clinical or laboratory evidence
      of associated systemic disease. The disease took a protracted course and all the
      children required long-term systemic immunosuppression (15-27 months), which was
      well tolerated. All children retained good vision and were either off treatment
      or on a small dose of immunosuppression at last follow-up. This condition,
      although rare, should be recognised in children as part of the differential
      diagnosis of acute orbital inflammation.

PMID- 8543075
TI  - Ocular protection in squash clubs: time for a change?
AB  - All squash clubs in the West Midlands were surveyed by postal questionnaire to
      determine their level of awareness to the risk of ocular injury. Of the 100 clubs
      surveyed, 51 questionnaires were returned. None of the clubs responding had any
      information warning of the potential hazards of ocular injury. Thirteen of the
      clubs had sporting goods shops; of these, three sold protective eye-wear.
      Significantly, all three stocked the open or lenseless type of eye-guard and only
      one had the guards with impact-resistant plastic lenses. The majority of clubs
      (96%) expressed a desire for further information. It is concluded that: (1)
      players are not warned of the hazards of playing without appropriate eye
      protection, (2) hazardous eye-guards (open type) continue to be sold, and (3)
      there is a desire to improve the safety of the sport.

PMID- 8543076
TI  - Long-term visual outcome following orbital decompression for dysthyroid eye
      disease.
AB  - The records of 33 patients who had undergone inferior and medial wall orbital
      decompressions for compressive optic neuropathy due to dysthyroid eye disease
      were reviewed. The indication for surgery in 32 patients was a reduction in
      Snellen visual acuity. The remaining patient had bilateral optic disc swelling
      but normal visual acuity. Twenty-nine patients (88%) were treated with systemic
      steroids pre-operatively, which resulted in an improvement in vision in all
      cases. In the immediate post-operative period visual acuity either improved or
      the steroid-induced visual improvement was maintained as the steroids were tailed
      off. Long-term visual outcome, however, varied. In 19 patients (58%) visual
      acuity was maintained with no requirement for additional treatment. In 12
      patients (36%) there was a subsequent deterioration in vision which responded to
      additional treatment with either systemic steroids, orbital radiotherapy or
      further orbital surgery. In 2 patients (6%) vision continued to deteriorate
      despite further treatment. We conclude that although orbital decompression has
      resulted in the long-term preservation of visual acuity in 94% of our patients,
      there remains a small subgroup (6%) in whom visual function continues to
      deteriorate despite all forms of treatment.

PMID- 8543077
TI  - Initial clinical experience with tissue plasminogen activator (tPA) assisted
      removal of submacular haemorrhage.
AB  - Tissue plasminogen activator (tPA) (250 micrograms/ml) was used to facilitate
      removal of submacular thrombus in 15 patients. Following a three-port vitrectomy
      and subretinal tPA injection (0.1 ml) via a 30 gauge needle, blood was evacuated
      after enzymatic dissolution for 20 minutes. Two injections were required in some
      cases. Nine women and six men were treated (mean age 75.5 +/- 8.6 years).
      Duration of symptoms ranged from 2 days to 8 weeks. One case was due to a retinal
      macroaneurysm, the others to age-related macular degeneration. Vision improved in
      13 patients and remained the same or deteriorated in 2 (mean follow-up 11 +/- 4.9
      months). Well-defined subretinal neovascular membranes were identified in 2
      patients and occult neovascularisation suspected in 2 others. A cataract
      developed in 1 case and retinal detachments in 2 others; all were treated
      successfully. The poor visual prognosis associated with submacular haemorrhage
      may be obviated by the use of the technique we describe.

PMID- 8543078
TI  - Sickle retinopathy in patients with sickle trait.
AB  - Sickle trait is traditionally considered a benign condition by ophthalmologists.
      Three cases of sickle retinopathy in subjects with sickle trait are reported. In
      all cases the onset of retinopathy was related to other contributing factors: in
      one case a traumatic hyphaema and raised intraocular pressure, in two others
      diabetes mellitus. Patients with sickle trait are at risk of retinopathy if
      coincident ocular or systemic disease is present.

PMID- 8543079
TI  - Herpes zoster chorioretinopathy.
AB  - Chorioretinitis and subsequent choroidal and retinal pigment epithelial atrophy
      following herpes zoster ophthalmicus (HZO) have rarely been reported. We report
      two patients, who several months following attacks of acute HZO, developed
      posterior fundus features of yellow, non-pigmented, punched-out areas of retinal
      pigment epithelial and choroidal pigment atrophy, which we have termed herpes
      zoster chorioretinopathy. An occlusive vasculitic process is proposed as the
      pathogenesis for this chorioretinopathy, and may be similar to that seen in the
      delayed cerebral vasculitis following HZO. A previous history of HZO should be
      sought in patients with a unilateral, multifocal, non-pigmented
      chorioretinopathy, as this may represent a characteristic delayed feature.

PMID- 8543080
TI  - T cell receptor V beta gene expression in experimental herpes stromal keratitis.
AB  - Our study examined T cell receptor (TCR) V beta mRNA expression in a murine model
      of experimental herpes simplex keratitis (HSK). We employed a polymerase chain
      reaction (PCR) technique to detect TCR V beta mRNA expression in the inoculated
      eyes of both HSK-susceptible and HSK-resistant mice at different time points
      after corneal inoculation with herpes simplex virus type 1 (HSV-1), followed by
      Southern blotting and densitometry analysis. In eyes from HSK-susceptible C.AL-20
      mice, a more diverse TCR V beta transcript usage pattern was detected as compared
      with that seen in HSK-resistant C.B-17 mice. V beta 8 family members were
      expressed in both strains of mice at days 11, 14 and 21 post-inoculation. By
      densitometry, at day 11, the intensity of expression of V beta 8.2 and V beta 8.3
      message was significantly greater in the eyes of C.AL-20 mice; V beta 8.1 was
      expressed only in C.B-17 mice. There were obvious differences in the TCR V beta
      expression between HSK-susceptible and HSK-resistant mice. The differences in the
      intensity of the message expressed by V beta 8 family members between the two
      strains could be correlated to previous experiments that showed V beta 8.1,2+ T
      cells as the main infiltrating cells in the corneas of HSK-susceptible mice by
      day 11 and 14 after challenge with HSV-1.

PMID- 8543081
TI  - Dynamics of external ocular blood flow studied by scanning angiographic
      microscopy.
AB  - The scanning angiographic microscope (SAM) provides a solution to the
      considerable technical difficulties associated with conventional episcleral
      fluorescein angiography. Standardised anterior segment fluorescein
      videoangiograms were performed using the SAM in each episcleral quadrant of the
      right eye in 6 normal subjects; frame-by-frame analysis proved important.
      Centripetal flow was seen in all 37 scleral perforating arteries investigated.
      Other features were the marked individual variability, much larger vertical
      anterior ciliary arteries, the high frequency of arteriovenous anastomoses, the
      complex flow patterns, the absence of a 'watershed' zone between anterior ciliary
      and posterior episcleral circulations, a characteristic and discontinuous
      distribution of 'leaky' episcleral veins, and the primacy of venous drainage into
      the plexus of muscular veins. Reports of retrograde blood flow in the anterior
      ciliary arteries in most fluorescein angiographic studies are probably incorrect,
      the result of unappreciated methodological problems. The SAM is an important
      advance on previous anterior segment fluorescein angiography techniques.

PMID- 8543082
TI  - Infrared thermography of the tear film in dry eye.
AB  - Infrared ocular thermograms were recorded for a group of 36 dry eye patients and
      for 27 age- and sex-matched controls. Mean ocular surface temperature was greater
      in the dry eye group (32.38 +/- 0.69 degrees C) compared with the control group
      (31.94 +/- 0.54 degrees C; p < 0.01). In addition, there was a greater variation
      of temperatures across the ocular surface in the dry eye group, illustrated by
      the difference in temperature between the limbus and the centre of the cornea
      (0.64 +/- 0.20 degrees C in dry eye patients compared with 0.41 +/- 0.20 degrees
      C in the control group; p < 0.001). This parameter was also shown to be greater
      in dry eye patients who displayed either a fast tear break-up time or a poor
      Schirmer's test result. Infrared thermography is a non-invasive and objective
      technique that may prove a useful research tool for study of the tear film, its
      deficiencies and its various treatment modalities.

PMID- 8543083
TI  - Role of cameral mucous gel in primary narrow angle and closed angle glaucoma: a
      pathogenic clue.
AB  - The cameral mucous gel (CMG) has been described as a layer of glycoprotein
      enriched hyaluronic acid lining the anterior surface of the iris, covering the
      trabecular meshwork, and spreading over the posterior surface of the cornea. The
      CMG is thought to exert a colloid-osmotic effect on the hydrostatic forces
      involved in the circulation of the aqueous humour which may help our
      understanding of the pathophysiology of open angle and angle closure glaucomas.
      The CMG was precipitated in two normal human eyes, one with an artificially
      shortened anterior chamber and the other with an open chamber. In the eye with a
      narrow angle, the CMG was seen to fill the iridocorneal gap completely, blocking
      access to the trabecular meshwork from the central anterior chamber. The CMG may
      be implicated in the pathogeny of narrow angle and closed angle glaucoma. The two
      types of glaucoma may share a common mechanism depending on the thickness of the
      layer of CMG that precedes the exit pathways. Pretrabecular CMG thickness is a
      decisive determinant of the colloid-osmotic resistance of the gel to aqueous
      outflow, and this thickness is governed by, among other factors, the position of
      the iris relative to the posterior surface of the cornea. The formation of a
      thick layer of CMG in the narrow chamber angle prevents the normal anterior
      chamber pressure from exerting a backward displacement effect on the peripheral
      iris. Unopposed posterior chamber pressure may therefore force the peripheral
      iris forward, making angle closure likely.

PMID- 8543084
TI  - Crossed polarising filters to measure relative afferent pupillary defects:
      reproducibility, correlation with neutral density filters and use in central
      retinal vein occlusion.
AB  - Measurement of a relative afferent pupillary defect (RAPD) can be carried out by
      attenuation of light received by the normal eye during the swinging flashlight
      test. Such measurements may be useful in the management of central retinal vein
      occlusion (CRVO). In this study a method employing cross polarised filters (CPFs)
      was tested for reproducibility. In addition the pattern of attenuation of light
      was compared with that by neutral density filters (NDFs). Finally, the method was
      used to investigate 74 patients with CRVO. The method was reproducible (8.7%
      variation) and showed exponential attenuation of light (in contrast to linear
      attenuation by the NDFs). In unilateral CRVO a sensitivity of 71% and specificity
      of 69% for the risk of iris neovascularisation was determined by the presence of
      RAPD requiring 20 degrees of rotation of the CPFs. It is concluded that CPFs
      provide a useful alternative to NDFs for the measurement of RAPD and have some
      advantages. They can be employed in the clinical management of patients with
      CRVO.

PMID- 8543085
TI  - Prospective study of adenovirus antigen detection in eye swabs by radioimmune dot
      blot.
AB  - Rapid laboratory diagnosis of ocular adenovirus infection is crucial in the
      containment of nosocomial transmission of the virus. In a large prospective study
      of adenovirus assay in eye swabs, antigen detection by radioimmune dot-blot
      (turnaround time 72 hours) achieved a sensitivity of 67% (239/355) and a
      specificity of 93% (3065/3285) in comparison with virus culture (median
      turnaround time 14 days). When specimens weakly reactive for adenovirus antigen,
      or equally reactive for both adenovirus antigen and Chlamydia trachomatis
      antigen, were considered falsely reactive in the adenovirus test, the sensitivity
      of the latter was reduced and false positive reactions were only marginally less
      frequent. The radioimmune dot-blot provides a more rapid diagnosis of ocular
      adenovirus infection than virus culture, but the high risk of false negative and
      in particular false positive results limits its clinical utility.

PMID- 8543086
TI  - Corneal perforation as a complication of epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is now recognised as a histopathologically
      distinct condition. Ocular complications of hereditary epidermolysis bullosa (EB)
      have been well documented, but little has been reported with respect to the
      ocular manifestations associated with the acquired form. A patient with EBA and
      sarcoidosis--an association that does not appear to have been previously reported
      -developed spontaneous peripheral corneal melting and perforation. The defect
      healed with the use of a bandage contact lens, antibiotics, mydriatics and pulsed
      intravenous steroids, and resulted in a satisfactory visual outcome.

PMID- 8543087
TI  - Chronic retinal toxicity due to quinine in Indian tonic water.

PMID- 8543088
TI  - Argon and YAG lasers in the treatment of ophthalmia nodosa.

PMID- 8543089
TI  - The eye and adenocarcinoma of the breast: metastases and meningiomas.

PMID- 8543090
TI  - Adenocarcinoma metastatic to the choroid: diagnosis by trans-scleral biopsy.

PMID- 8543091
TI  - Proptosis precipitated by retinal detachment repair in a patient with occult
      pituitary tumour.

PMID- 8543092
TI  - Tuberculosis presenting as an orbital mass lesion in childhood.

PMID- 8543093
TI  - Cutaneous malignant melanoma metastatic to the choroid: a clinicopathological
      case report.

PMID- 8543094
TI  - Bilateral orbital metastases from breast carcinoma masquerading as thyroid eye
      disease.

PMID- 8543095
TI  - Visual loss in metastatic sclerochoroidal calcification.

PMID- 8543096
TI  - Bilateral ptosis, tonic pupils and abducens palsies following Campylobacter
      jejuni enteritis.

PMID- 8543097
TI  - Alkaline chemical ocular injury from Emla cream.

PMID- 8543098
TI  - Retinal haemorrhage in meningitis.

PMID- 8543099
TI  - Maculopathy associated with diazepam.

PMID- 8543100
TI  - Ensuring graft centration using a modified YAG laser.

PMID- 8543101
TI  - Factors affecting the outcome of children treated for amblyopia.

PMID- 8543102
TI  - Transitional cell carcinoma of the bladder metastatic to the orbit.

PMID- 8543103
TI  - Orbital myositis.

PMID- 8543104
TI  - Degradation of Mersilene sutures.

PMID- 8543105
TI  - Routine obstetric ultrasound.
AB  - A detailed review of the literature reveals that routine obstetric ultrasound has
      value in providing more accurate gestational dating and in the diagnosis of fetal
      anomalies. The recent RADIUS study, which has concluded that routine obstetric
      ultrasound is of no clinical benefit, is critically analyzed, focusing on four
      areas: the applicability of the results to the general population, the
      appropriateness of the outcome parameters, the quality of the ultrasound
      provided, and the issue of excessive cost. Finally, an ethical analysis of the
      role of routine obstetric ultrasonography is provided, focusing on the principles
      of beneficence and respect for autonomy. The offering obstetric ultrasound is
      necessary in both beneficence-based and autonomy-based ethical analyses, and the
      use of routine ultrasound is supported from an analysis of the scientific data.

PMID- 8543106
TI  - Oxytocics in developing countries.
AB  - OBJECTIVES: A prospective multicenter study of obstetric practices was conducted
      in three developing countries (Benin, Congo and Senegal) to analyze oxytocic use
      during labor. One of the objectives was to assess the possible negative effects
      of the treatment regimens instituted during the labor monitoring phase. METHODS:
      Four health districts participated in the study. All women who gave birth in one
      of the participating health facilities over a 6-month period in Benin and Congo,
      and over a 3-month period in Senegal, were recruited. The number of deliveries
      studied in each district varied from 457 to 1048. For each case a partogram was
      used to assess the progress of labor and the onset of dysfunctional labor.
      Information was collected on the risk factors for dysfunctional labor,
      stillbirths and resuscitation of the neonate. RESULTS: Each of the four
      collaborating centers used oxytocics preferentially to treat dysfunctional labor,
      but even in normal labor (i.e. with a normal partogram) oxytocics were used in
      4.4-21.5% of cases. In normal labor the incidence of neonatal resuscitation was
      higher in cases with than in those without oxytocic use: the relative risks
      (R.R.) varied from 1.9 to 5.6; the odds ratios varied from 2.4 to 7.0, and both
      were statistically significant in the four settings. In addition the stillbirth
      rate was always higher, though not significantly, when oxytocics were used in
      normal labor (R.R. 1.2-2.2). When the data of the four centers were pooled, the
      global relative risk for stillbirths was 1.9, and the 95% confidence interval was
      1.1-3.4. Logistic regression analysis was carried out for five confounding
      factors (primiparity, a previous complicated delivery, presence of meconium,
      ruptured membranes and educational level) to adjust the odds ratio for the risk
      of neonatal resuscitation when oxytocics were used in normal labor. Except in the
      case of Abomey in Benin, where the variable 'presence of meconium' decreased the
      odds ratio from 6.4 to 3.4, the adjusted odds ratios remained similar to their
      non-adjusted values. In cases of non-dysfunctional labor, nurses and midwives
      used oxytocics more often than lesser trained health personnel (R.R. 4.0 [3.2
      5.1]). CONCLUSION: Our results show that an obstetric treatment which is safe
      when used in certain well-defined indications, may have significant negative
      effects when used in situations where the same technical quality of care cannot
      be guaranteed.

PMID- 8543107
TI  - The intrauterine ponderal index in relation to birth weight discordance in twin
      gestations.
AB  - OBJECTIVE: To establish the relationship between the fetal ponderal index and
      birth weight discordance in twins. METHOD: The fetal ponderal index (estimated
      fetal weight divided by femur length3) was calculated in 86 pairs of twins
      delivered within 2 weeks of the last sonography and analyzed in relation to birth
      weight discordance. RESULTS: A weak but significant correlation between fetal
      ponderal index and birth weight (r = 0.26, P < 0.0007) but no correlation with
      gestational age (r = 0.035, P = 0.65) were found. Members of concordant pairs (<
      15% birth weight difference) had a significantly higher fetal ponderal index
      compared with members of mildly (15-25%) discordant pairs (P < 0.02), but not as
      compared with members of severely discordant (> 25%) pairs. CONCLUSION: The
      characteristics of the fetal ponderal index in twins are similar to those in
      singletons. Fetal size seems to be diminished in severe but not in mild
      discordants. However, in its present form, the fetal ponderal index is a poor
      predictor of discordant growth and therefore should be employed cautiously in
      twin gestations.

PMID- 8543108
TI  - Postpartum hysterectomy.
AB  - OBJECTIVES: To review cases of postpartum hysterectomy regarding indications,
      risk factors and complications and compare them with cases of emergency cesarean
      section. METHODS: We conducted a retrospective chart review study of 20 cases of
      postpartum hysterectomy and 20 cases of emergency cesarean section performed at
      Sinai Samaritan Medical Center, Milwaukee, Wisconsin, between January 1984 and
      January 1994. Emergency postpartum hysterectomies were compared with emergency
      cesarean sections regarding obstetric history, placental location, operative
      time, blood loss, blood transfusion, intra- and postoperative complications and
      length of hospitalization. Emergency hysterectomies were reviewed according to
      their indications for the incidence of complications and length of
      hospitalization. Pathological diagnoses of the hysterectomy specimens were
      reviewed. Statistical analyses were performed using the two-tailed Student's t
      test and Fisher's exact test. RESULTS: Placenta accreta was the most common
      indication for emergency postpartum hysterectomy. Prior cesarean section and/or
      placenta previa were risk factors. Emergency hysterectomies were associated with
      longer operating times (P < 0.0001), greater blood loss (P < 0.0001), more
      transfusions (P < 0.001), postoperative complications (P < 0.01), secondary
      surgeries (P < 0.01) and longer hospitalizations (P < 0.0001) than cases of
      emergency cesarean section. CONCLUSIONS: Emergency postpartum hysterectomy is
      associated with significant blood loss, need for transfusion, postoperative
      complications and longer hospitalization partly because of its indications. The
      combination of prior cesarean section and current placenta previa should alert
      the obstetrician that an emergency postpartum hysterectomy may be needed.

PMID- 8543109
TI  - Coagulation and plasma fibronectin parameters in HELLP syndrome.
AB  - OBJECTIVES: HELLP syndrome (hemolysis, elevated liver enzymes and low platelets)
      has a high fetal mortality and maternal morbidity, partly due to its late
      diagnosis. In order to facilitate earlier diagnosis, we studied the changes
      occurring in natural coagulation inhibitors, fibronectin and haptoglobin as
      potential early markers of endothelial damage, coagulation cascade activation and
      intravascular hemolysis. METHODS: The study compared antithrombin (AT-III),
      protein C and S activity, plasma fibronectin, 'prothrombin time' and 'partial
      prothrombin time' (AST, ALT), lactate dehydrogenase (LDH), bilirubin and serum
      haptoglobin in 17 asymptomatic controls, 19 preeclampsia patients and 11 HELLP
      syndrome patients. RESULTS: HELLP syndrome patients had higher fibronectin and D
      dimer values, lower AT-III and protein C activity, a lower platelet count and
      higher LDH than healthy controls; only 25% had raised bilirubin. Serum
      haptoglobin was lower in HELLP syndrome. CONCLUSIONS: Early on in HELLP syndrome,
      there is probably a pro-coagulatory imbalance in the placental microcirculation.
      Endothelial damage causes tissue thromboplastin release and coagulation cascade
      activation due to collagen exposure; the vascular lesion increases thromboplastin
      in the bloodstream and triggers distant coagulation processes, suggesting
      compensated disseminated intravascular coagulopathy. Measuring plasma fibronectin
      and coagulation inhibitors should be supported by testing haptoglobin as a marker
      of intravessel hemolysis to differentiate conventional preeclampsia from HELLP.

PMID- 8543110
TI  - Serum CA 125 levels before, during and after treatment for endometriosis.
AB  - OBJECTIVES: The aim of this study was to assess the treatment of endometriosis
      with a gonadotropin-releasing hormone (GnRH) agonist in terms of changes to the
      extent of disease and to CA 125 levels as well as to recurrence during follow-up.
      METHODS: The levels of serum CA 125 were evaluated in 66 patients with
      endometriosis diagnosed and staged by laparoscopy according to the revised
      American Fertility. Society classification, who received a 6-month course of a
      GnRH agonist. Serum CA 125 levels were measured before, during (3 and 6 months
      after the initiation of therapy) and 6 months after cessation of therapy.
      RESULTS: Patients with minimal and mild endometriosis had significantly higher
      mean pretreatment values than control subjects in the luteal phase of the cycle
      or than postmenopausal women (P < 0.05), but the overall mean value was still
      below 35 U/ml. Levels of CA 125 fell during treatment to those found in normal
      controls, but rose again after the end of treatment. The sensitivity and
      specificity of CA 125 were 75% and 83.3%, respectively, and its positive
      predictive value as a marker of recurrence was 46.36%. CONCLUSION: These data
      suggest that CA 125 may be a reliable indicator for monitoring the efficacy of
      GnRH agonist treatment of endometriosis, but its value as a predictor of
      recurrence is low, probably due to the suppression of all CA 125 sources such as
      endometrium, ovaries and implants.

PMID- 8543111
TI  - Adenomatoid tumor of the female genital tract.
AB  - OBJECTIVE: To remind gynecologists of the diagnosis of adenomatoid tumor of the
      female genital tract, a pathology which is often mistaken for leiomyoma, and in
      addition to warn of the malignant appearance of adenomatoid tumor. MATERIALS AND
      METHODS: During the study period from January 1988 to May 1994, the clinical
      features and pathologic findings of 25 cases of adenomatoid tumor of the female
      genital tract were reviewed at the National Taiwan University Hospital. RESULTS:
      The age of the patients ranged from 26 to 55 years with a median of 41 years.
      Adenomatoid tumor was an incidental finding during the surgical treatment of
      myoma (16 cases), cervical intraepithelial neoplasm (two cases), invasive
      cervical cancer (one case), adnexal cyst (five cases), and pregnancy with myoma
      (one case). Twenty-three cases had tumors in the uterine corpus and two in the
      fallopian tubes. Twenty percent of the patients had multiple tumors. Their sizes
      ranged from 1.0 to 8.0 cm. The case with the largest tumor measuring 8 cm in
      diameter is presented in detail. Its histologic, immunohistochemical and
      ultrastructural characteristics strongly support the mesothelial origin of
      adenomatoid tumor. CONCLUSION: Some different results were obtained than those
      hitherto reported in the literature, such as younger age, frequency of multiple
      tumors, and fewer cases accompanied by leiomyomas.

PMID- 8543112
TI  - Hemostatic radiotherapy in carcinoma of the uterine cervix.
AB  - OBJECTIVE: To evaluate the treatment of hemorrhagic carcinoma of the uterine
      cervix with hemostatic radiotherapy (external and intracavitary radiotherapy).
      METHOD: Twenty cases of refractory hemorrhagic carcinoma of the uterine cervix
      receiving hemostatic radiotherapy between April 1987 and May 1992 were analyzed.
      The age of the patients ranged between 30 and 60 years with a median of 42 years.
      RESULTS: The mean tumor volume was 130 mm3; all cases were classified as FIGO
      stage IIb (n = 8), IIIb (n = 11) or IVa (n = 1). Radiotherapy was carried out
      either by the external or intracavitary technique. The control of hemorrhage was
      100% within 12-48 h after radiotherapy. However 85% of patients failed locally in
      the form of residual, recurrent pelvic or metastatic disease, within 24 months of
      follow-up. CONCLUSION: Hemorrhagic cervical cancer has a poor prognosis.

PMID- 8543113
TI  - Delayed interval delivery in quadruplets.
AB  - Prolonged interdelivery periods in preterm twin and triplet gestations have
      resulted in a good outcome for the fetus(es) remaining in utero. This is the
      second reported case of delayed delivery intervals in quadruplets who were born
      on 3 separate days. We report on a set of quadruplets following gonadotropin
      induction of ovulation, in which preterm delivery of the first infant occurred at
      26 weeks' gestation. Active uterine contractions ceased and ultrasonography
      confirmed the remaining triplets to be in separate amniotic sacs with
      satisfactory heart rate tracings. With bed rest and tocolysis, the delivery of
      the second infant did not occur until 8 days later. After a further 36-h delay,
      placental abruption prompted cesarean delivery of the remaining twins. The first
      infant died of sequelae of prematurity at 7 months, while the remaining triplets
      survived and are neuro-developmentally normal 1 year after delivery. This report
      demonstrates the feasibility of prolonging the delivery interval of the fetus(es)
      in higher order multiple gestations, using tocolysis and watchful expectancy,
      after the preterm birth of one or more fetuses.

PMID- 8543114
TI  - Short rib polydactyly syndrome--a rare skeletal dysplasia.
AB  - We present a case of prenatal ultrasonographic diagnosis of short rib polydactyly
      syndrome (SRPS). The fetus had severe oligohydramnios due to bilateral renal
      agenesis. Amnioinfusion with normal saline improved ultrasound visualization and
      helped in confirming the diagnosis. Subtypes and differential diagnosis of SRPS
      are discussed.

PMID- 8543115
TI  - Treatment of fetal supraventricular tachycardia with maternal administration of
      digoxin.

PMID- 8543116
TI  - Maternal tetanus toxoid immunization records.

PMID- 8543117
TI  - Myotonic dystrophy in pregnancy.

PMID- 8543118
TI  - Labor experience and beta-endorphin levels.

PMID- 8543119
TI  - Suprapubic drainage following operative pelviscopy.

PMID- 8543120
TI  - ACOG technical bulletin. Preterm labor. Number 206--June 1995 (Replaces No. 133,
      October 1989).
AB  - Premature delivery is the leading cause of perinatal mortality and long-term
      neurologic morbidity. Despite intensive efforts, prematurity rates remain
      unchanged. Although different forms of therapy, such as tocolytic therapy and
      home uterine activity monitoring, are being used to prevent prematurity, their
      true benefit and the proper place for their application remain to be established.
      Continued efforts at risk identification, accurate and early diagnosis, and
      prompt intervention hold the most promise for prevention of premature delivery.
      In addition, when preterm birth is imminent, intensive intrapartum care and
      delivery in a location where access to the appropriate level of neonatal
      intensive care is available will optimize perinatal outcome.

PMID- 8543121
TI  - [Transposition of the fallopian tube as a therapeutic possibility in special
      cases of tubal sterility].

PMID- 8543122
TI  - [Rheumatic diseases in pregnancy--problems from the viewpoint of the
      gynecologist].

PMID- 8543123
TI  - [Prenatal auditory perception--on the relevance of new concepts of perception].

PMID- 8543124
TI  - [Should maternal guidelines be improved?].

PMID- 8543125
TI  - [Diagnostic value of color Doppler ultrasound in breast tumors].
AB  - The aim of this study was the validation of the minimal Resistance Index (min RI)
      measured by colour Doppler sonography as parameter of tumour neoangiogenesis. 107
      patients with clinically or radiologically diagnosed breast tumour with a
      sonographically detectable lump had preoperative measurements and analysis of
      blood flow in the tumour area and in the healthy parenchyma of both breasts. The
      min RI was compared with histology, menopausal status and age. In all 107
      patients blood flow could be measured in the tumour area and in 98% of the
      bilaterally investigated quadrants. Irrespective of tumour status the mean min RI
      was lower in the tumour area (0.62) than in the other quadrants of the affected
      (RI = 0.65, p = 0.002) or contralateral breast (RI = 0.65, p = 0.0003). The mean
      min RI of benign tumours was 0.60 (+/- 0.11 SD) and of malignant tumours 0.64 (+/
      0.11 SD), this difference was not significant (p = 0.07). Irrespective of tumour
      status postmenopausal patients had a higher mean min RI than premenopausal
      patients. This was true for the tumour area (RI = 0.64 vs 0.60, p = 0.11) and
      also for the quadrants (RI = 0.68 vs 0.62, p = 0.0002). In postmenopausal women
      there was a statistically significant correlation with age (r = 0.58, p =
      0.0001). We conclude that the min RI is of no diagnostic relevance for the
      classification of breast tumours as benign or malignant.

PMID- 8543126
TI  - [Displacement margins and edge contour: informative criteria of tumor dignity in
      ultrasound mammography].
AB  - 88 patients with ultrasonically detected breast tumours were examined at the
      Department of Obstetrics and Gynaecology of the Technical University Aachen
      (RWTH) in the context of a prospective study. Ultrasonic contour characteristics
      and marginal zone displacement properties were evaluated with regard to their
      usefulness as criteria for detecting malignancy. using a highresolution hand-held
      10 Mhz scanner. With regard to marginal zone displacement as a sign of
      benignancy, a sensitivity of 67.6% and specificity of 86.3% were found (positive
      and negative predictive value reaching 89.3% and 86.3%, respectively). A
      sensitivity of 84.3% and specificity of 86.5% could be demonstrated when an ill
      defined, jagged contour was taken as a sign of malignancy. A well-defined, smooth
      contour resulted in a sensitivity and specificity of 62.2% and 100%,
      respectively, when used as criterion for benignancy. No clear indication could be
      found to support the use of an ill-defined but smooth contour as a sign of
      benignancy. 56.3% showing the aforementioned characteristic were benign, the rest
      (43.7%) were malignant neoplasias. The evaluation of ultrasonic contour
      characteristics and marginal zone displacement properties are hence fundamental
      criteria to augment other characteristic tumour signs in the ultrasonic diagnosis
      of breast pathology.

PMID- 8543127
TI  - [The value of aspiration cytology within the scope of triple diagnosis of
      palpable breast changes].
AB  - The diagnostic value of aspiration cytology and the overall diagnostic quality of
      the so-called triple test (aspiration cytology, mammography and physical
      examination) in the evaluation of palpable breast masses were investigated in a
      retrospective study. 608 histologically evaluated cancers and 224 benign lesions
      were investigated. A main purpose of the study was to find out whether the triple
      diagnostic test can replace surgical biopsy and thereby reduce the number of
      unnecessary biopsies. All lesions triple-diagnosed as malignant were
      histologically proved to be malignant, i.e. there were no false positive results.
      The rate of false negative results was found to be within the range reported for
      false negative results in fresh frozen sections. Based on these results we state
      that the dogmatic statement "every palpable mass in the breast must be excised"
      should be replaced by the recommendation "every palpable mass must be assessed
      and clarified". A great number of retrospectively unnecessary biopsies can be
      avoided by a systematic use of the triple diagnosis. The diagnostic safety of
      this method is close to that of open biopsy. In all cases where positive or
      negative concordant triplets are found, histological confirmation by biopsy can
      be avoided. Patients with benign lesions can be thoroughly followed up by
      repeated physical and radiological examinations. Patients with triple diagnostic
      malignant results can be adequately treated. Lesions for which triple diagnosis
      yields neither benign nor malignant, must be biopsied: This is also necessary in
      all cases with suspicious findings in mammography without a palpable mass, if the
      equipment for stereotactic or ultrasound- guided biopsies is not
      available.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8543128
TI  - [Quality assurance by improved cooperation structures. The example of
      decentralized early detection mammography].
AB  - The German Mammography Study investigated into quality assurance measures for
      screening mammography, proceeding in a decentralised manner and focussing
      especially on structure, process and outcome of the study. The field phase lasted
      for three years, and during this period the technology of the equipment used in
      mammography improved, also to the indicators of process and of early outcome. The
      annual interval of examinations was well received. To include mammography into
      the German cancer screening programme is no easy matter: it requires a
      comprehensive cooperative quality assurance programme incorporating various
      institutions of medical care. Appropriate recommendations have been made to the
      Federal Committee of Physicians and Sickness Insurance Bodies.

PMID- 8543129
TI  - [C-erbB-2, EGF receptor, p53 and PCNA. The prognostic significance of recent
      tumor markers for lymph node negative breast cancer].
AB  - In 216 breast cancer patients, the prognostic value of current biological factors
      (c-erbB-2, EGF-receptor, p53, PCNA-proliferative fraction) was compared with that
      of conventionally histomorphologic features (histologic type, histologic grade,
      tumour size, hormonal receptor status). After a 66(6 - 109) months' median follow
      up survival was significantly correlated with histological grade (p = 0.014) and
      PCNA-proliferative activity (p = 0.015). The prognostic influence of oestrogen
      receptor (ER)- and progesteron receptor (PR-)status achieved borderline
      significance (ER/p = 0.07; PR/p = 0.05). Neither c-erbB-2, EGF-R, p53 nor any of
      the other factors showed any correlation to survival. In the multivariate
      analysis, histological grade was revealed as the only independent prognostic
      factor. The prognostic value of PCNA was second to histological grade and if
      grade was excluded from the analysis, PCNA-expression became the only independent
      factor. Thus, in individual cases the PCNA-proliferative fraction could help the
      clinician to decide on the therapy.

PMID- 8543130
TI  - [Responsibility for patient education and incidence of homologous blood
      transfusions in unilateral breast cancer operations].
AB  - According to a judgement by the German Federal Court of 17 December 1991 the
      surgeon is legally bound to inform the patient before hand of the risk of a
      possible homologous blood transfusion during surgery. If the transfusion
      probability exceeds 5%, this obligation is really relevant, 228 patients with
      primary breast cancer of stage pT1 - 3N0 - 2M0 had been treated either radically
      (n = 146) or by a breast-preserving operation (n = 82) from January 1989 to
      December 1993. 400 to 800 ml erythrocyte preparations had been placed at disposal
      in advance for each patient. The rate of blood transfusions, pre- and
      postoperative haemoglobin (Hb), age, tumour size, lymph node involvement, kind
      and duration of operation as well as postoperative course have been analysed 43
      of 228 (18.9%) patients received a homologous blood transfusion within 24 hours
      after operation. Transfusion rate per year decreased from 39.4% (1989) to 44.8%
      (1990), 12.2% (1991), 16.6% (1992) and 3.1% in 1993. On the contrary mean pre-and
      postoperative haemoglobin levels did not differ significantly (p < 0.05) between
      the different years: 13.4 +/- 0.8 respectively 12.1 +/- 1.1 g/dl (1989) and 13.5
      +/- 1.3 respectively 12.1 +/- 1.3 g/dl (1993). Patients who had transfusions were
      significantly (p < 0.05) more likely to suffer from preoperative anaemia and
      larger tumors, and they have been treated by mastectomy more frequently compared
      to patients without transfusion. There were no correlations between transfusions
      and age, tumour size, lymph node involvement, kind and duration of
      operation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8543131
TI  - [Prenatal determination of fetal rhesus factor in amnionic cells using polymerase
      chain reaction].
AB  - In Rhesus incompatibility, prenatal RhD typing of the fetus requires intrauterine
      blood sampling by cordocentesis or by chorionic villus biopsy. Amniocentesis is
      easier to perform, and carries a lower risk of enhancement of maternal
      immunization. Therefore, we evaluated polymerase chain reaction (PCR) for fetal
      RhD typing in amniocytes which were isolated from amniotic fluid (18-40 gw)
      obtained by amniocentesis (n=26) or during delivery (n=27). In the clinically
      most important group of children from RhD-negative women (n=25) and in 28
      newborns of RhD- positive mothers, we found a 100 percent agreement between the
      findings of PCR and the results of serologic typing. If these encouraging results
      are confirmed in a larger series, the method could be used for the clinical
      management of RhD-negative women with Rhesus incompatibility and a heterozygous
      RhD-positive partner.

PMID- 8543132
TI  - [Kallikrein (urine) in pregnancy-induced hypertension].
AB  - Total, active and inactive renal kallikrein were compared between 25 patients
      with hypertensive disorders of pregnancy and 25 healthy pregnant women of
      corresponding gestational age. Values of all three fractions were twice as high
      in healthy women than in hypertensive patients and differed with statistical
      significance. A longitudinal examination of renal kallikrein during pregnancy
      showed a physiological decrease of values from the 16th-20th week until term.
      Asymptomatic women, who developed hypertension later on, showed decreased renal
      kallikrein values.

PMID- 8543134
TI  - [Diagnosis and therapy of fetal alloimmune thrombocytopenia].
AB  - In fetal alloimmune thrombocytopenia, maternal IgG antibodies directed against
      platelets pass into the fetal circulation and lead to the destruction of fetal
      platelets. Fetal thrombocytopenia is usually first noted postnatally, but the
      maternal alloantibodies may lead to severe fetal haemorrhage in utero in the
      second or, more commonly, third trimester. Platelet-specific antibodies appear to
      play the major role in the pathogenesis of fetal alloimmune thrombocytopenia.
      Antenatal serological diagnosis is complicated by the fact that no platelet
      specific alloantibodies are detectable in untreated maternal serum in about 20%
      of cases. Even when antibodies are detected, repeated estimation of the titre in
      the mother gives no indication of the severity of the fetal thrombocytopenia.
      Therefore, when the diagnosis of fetal alloimmune thrombocytopenia is suspected,
      it should be confirmed and subsequently monitored by cordocentesis. The
      intrauterine transfusion of compatible platelets and the administration of high
      dose IgG infusions to the mother and/or fetus are currently being used as
      approaches to treatment. Despite advances in the antenatal diagnosis and therapy
      of fetal alloimmune thrombocytopenia, the clinical effects on the fetus remain
      unpredictable.

PMID- 8543133
TI  - [Pregnancy and labor in idiopathic thrombocytopenic purpura].
AB  - Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura
      (ITP) were retrospectively analyses. The mean age of the women was 28.2 years.
      Five women underwent splenectomy during childhood. The lowest maternal platelet
      count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only
      one case. Treatment was based on administration of corticosteroids with or
      without human-pooled immunoglobulins. Caesarian section was performed in all
      cases. Six newborns were healthy and had a successful subsequent course. Two
      infants died, one in utero because of abruptio placentae and the other one 1
      month post partum because of a cerebral haematoma. After a mean follow-up of
      eighteen months, thrombocytopenia is still present in two women, despite the
      continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy.
      Treatment is usually successful for the mother but the risk for the fetus remains
      considerably high.

PMID- 8543135
TI  - [Uterine rupture during induced abortion with prostaglandins in the second
      trimester].
AB  - Based on our own experiences and on the literature of the past 14 years the
      variety of the presenting symptoms in patients suffering from ruptured uterus
      during the second trimenon are discussed. focussing especially on the first
      symptoms of a so-called "silent" uterus rupture. A 41-year old second gravida,
      first para--the healthy full-term child was delivered by Caesarean section-
      suffered a "silent" uterus rupture after termination of pregnancy at 20th/21st
      weeks' gestation. As more than 50 per cent of patients with "silent" uterus
      rupture are diagnosed with considerable delay, early and repeated ultrasound
      examinations should be performed in all patients with unexplained symptoms or if
      despite abortion induction for several days no progression of birth occurs. In an
      artificially induced abortion, prostaglandins should be topically applied to
      enhance cervix ripening, preferably as a biphasic treatment (first for cervix
      ripening, later induction of contractions). It is not yet clear whether a single
      or total dose reduction of prostaglandins used in labour induction in the second
      trimenon may help to prevent uterus rupture in patients at risk. Predisposing
      risk factors must be taken into account before applying prostaglandins. Uterus
      rupture should always be considered as differential diagnosis if problems occur
      in patients after induced abortion in the second trimenon.

PMID- 8543136
TI  - [Septic abortion in Campylobacter jejuni infection].
AB  - Case report of a 24 year old woman II G/I P with enterocolitis and septicaemia
      caused by Campylobacter jejuni (C.) in the following time abortion at 16 weeks of
      gestation. Diagnostics, therapy, review of literature.

PMID- 8543137
TI  - [Intravenous leiomyomatosis].
AB  - A 49-year-old woman presented with a uterine tumour with solid and cystic parts.
      Extension of the tumour into the broad ligament was noted at the operation with
      wormlike plugs of tumour within the veins. The histological diagnosis of
      intravenous leiomyomatosis was evident. The disease turned out to be far
      advanced: a long continuous intraluminal mass extending from the iliac veins to
      the right ventricle made a second operation with thoracotomy and laparotomy
      mandatory. Postoperative follow-up showed so far, 1.5 years after operation, no
      evidence of recurrence. Intravenous leiomyomatosis is a very uncommon finding.
      Though it is histologically a benign smooth-muscle tumour, the biological
      behaviour with intravenous growth which may involve the right side of the heart,
      is quite aggressive. About 100 cases were reported in the literature; in no case
      could the diagnosis be made before surgery.

PMID- 8543138
TI  - [Intraspecific genetic diversity: monitoring and principles of conservation].
AB  - Genetic differentiation of a species, estimated on average according to the
      aggregate of allozyme loci, corresponds to a selectively neutral process. Such
      evolution is traditionally regarded as Markov's chain, in which the genetic
      dynamics of a population cannot be predicted for more than one generation.
      According to the concept of population systems, however, intraspecific
      differentiation can be interpreted as a process with memory, which retains
      information about the genetic structure of the ancestral population. This memory
      is maintained due to the organizing effect of gene immigration whose intensity is
      the higher, the lower the effective size of the local population. The ratio
      between intra- and inter-population components of gene diversity is maintained at
      a stable (optimal) level. Consequently, it can be regarded as the basic
      "reference point" in genetic monitoring of subdivided populations that have
      evolved under anthropogenic pressure. Such influences, altering established
      systemic links, distort the balance between differentiation and integration of
      the species gene pool and lead to adverse effects. Depending on the predominance
      of the inter- or intra-population component of gene diversity, these influences
      may be equivalent to outbreeding with an increased segregational load or to
      inbreeding, respectively. In the first case, the genetic process is adaptive,
      and, provided the negative influence is terminated in due time, it is possible to
      restore the genetic structure and normalize reproduction of gene pools in
      populations. In the second case, the genetic process is maladaptive and leads to
      degradation of populations. If one knows principles of the systemic organization
      of a species, it is possible to develop an approach to solving the problem of
      conservation of biological diversity by organizing non-exhaustive wildlife
      management.

PMID- 8543139
TI  - [Genetic polymorphism in barley detected by arbitrary primers].
AB  - Genetics and breeding studies require effective methods for polymorphism analysis
      that allow one to classify varieties and to determine phylogenetic interactions
      between plant species. A variant of the polymerase chain reaction for DNA
      amplification with arbitrary primers (RAPD) was used to determine genetic
      distances between Hordeum vulgare varieties and to integrate of the varieties
      into groups. The dendrogram of relations between species from the genus Hordeum
      and species of some cultivated cereals was constructed on the basis of RAPD
      analysis.

PMID- 8543140
TI  - [Introns differ from exons by their redundancy].
AB  - This paper is devoted to an analysis of the intrinsic structure of the gene from
      the point of view of the redundancy of different structural units--exons and
      introns. Human genes for which the exon-intron structure has been clearly
      established were studied. The redundancy of each exon and intron in the gene was
      determined. It was shown that, in human genes, introns are more redundant than
      exons. Redundancy is determined as the smallest length of a word
      (oligonucleotide) beginning with which all words in the studied nucleotide
      sequence are found exactly once. Mechanisms leading to the disruption of the
      general pattern of ratios of redundancy of exons and introns are studied.

PMID- 8543141
TI  - [Polymorphism at codon 117 of the granulocyte-macrophage colony-stimulating
      factor (GM-CSF) gene].
AB  - A T-to-C substitution, replacing a hydrophobic isoleucine residue with a
      hydrophilic threonine residue in position 100 of a mature protein molecule, was
      found at codon 117 of the GM-CSF gene. The mutation frequencies were estimated in
      51 DNA samples from healthy adult donors and also in 20 samples from patients
      with different neoplastic myeloid disorders. Almost equal substitution
      frequencies in patients and normal individuals were observed, suggesting that the
      defect was not associated with leukemia. Additionally the GM-CSF gene intron 1
      sequence was refined.

PMID- 8543142
TI  - [Mucoid clones of Pseudomonas aeruginosa PAO1, surviving after induction of
      prophage transposons].
AB  - The origin and properties of mucoid clones were studied. The clones were selected
      with high frequency after thermo-induction of Pseudomonas aeruginosa lysogenic
      for phage transposons (PT). The production of alginate does not promote the
      survival of lysogenic bacteria at 42 degrees C. Mucoid clones were shown to
      appear before thermo-induction; the frequency of their formation does not depend
      on the specificity of the mutator effect intrinsic to different PT. Phenotypic
      differences typical of mucoid clones can be mediated by different mutations
      promoting clone survival at 42 degrees C and by simultaneously arising additional
      mutations. The SL21 mucoid clone selected among clones of P. aeruginosa PAO1
      resistant to PT of B3 possesses an additional trait of phage resistance at 42
      degrees C. The presence of D3112 cts 15 prophage has no significant effect on the
      frequency of SL21 reversion to nonmucoidness. This means that the mutator effect
      of PT has made a slight contribution to this process. The appearance of mutations
      promoting the survival of the thermoinducible lysogen SL21 (D3112 cts 15) does
      not affect the frequency of the loss of mucoidness. Nonmucoid derivatives of SL21
      were shown to differ in phage resistance at 42 degrees C and in the extent of the
      residual mucoidness manifested under specific conditions. Consequently, nonmucoid
      clones appear as a result of pseudo-reversions. Because some of these pseudo
      revertants cannot again be converted to the mucoid form, it is concluded that
      they carry mutations in genes whose functions are obligatory for the production
      of alginate.

PMID- 8543143
TI  - [Starvation-induced mutagenesis in Salmonella typhimurium].
AB  - Spontaneous reversion to prototrophy of two his alleles of Salmonella typhimurium
      -hisG428 (ochre) and hisC527 (amber)--was studied. Strains containing hisG428
      allele in the chromosome and within the multicopy plasmid pAQ1 were used. When
      the hisG428 allele was chromosomally located, no sharp fluctuations in the number
      of His+ revertant were observed in fluctuation experiments and the distribution
      of revertants obeyed the Poisson law. The pattern of revertants distribution in
      strains carrying plasmid pAQ1 was intermediate between the Poisson distribution
      and jackpot distribution described by Luria and Delbruck. Conversely, sharp
      fluctuations were observed in the distribution of His+ revertants of the hisC527
      allele obtained from independent cultures. The data presented here suggest that
      His+ revertants, including ochre suppressors, appear under the influence of
      histidine starvation, when the hisG428 allele is chromosomally located. At the
      same time, reversion to prototrophy at the hisC527 allele does not strictly
      depend on the presence or absence of this amino acid in the medium. Plasmid
      location and novobiocin-resistance mutation promoted the identifying of
      preexisting mutants among His+ revertants of the hisG428 allele. The data
      obtained also demonstrate that the presence of the mutator plasmid pKM101
      preferentially increases the frequency of adaptive His+ reversions.

PMID- 8543144
TI  - [Population sturcture of the Gorno-Mariiskii region of the Marii El Republic].
AB  - The genetic structure of the population of the Gorno-Mariiskii raion, Marii El
      Republic, was studied. The population consists of two major groups, highland Mari
      and Russians. The former constitute the majority of the rural population, and the
      latter, the majority of the urban one. A marked ethnicity-related marriage
      assortation was found. The value of random inbreeding was estimated using
      frequencies of surnames. It varied from 0.00015 to 0.00069 (the weighted average
      was 0.00026). The local inbreeding (a) for Gorno-Mariiskii raion estimated
      according to Malecot was 0.00029. The local inbreeding for marriages between Mari
      (0.0022) was five times higher than for marriages between Russians. The indices
      of endogamy were 0.84 in the rural population and 0.14 in the urban population.
      The matrix of genetic distances and its image in the form of genetic landscape
      suggest a regularly distorted isolation by distance and realized panmixia.

PMID- 8543145
TI  - [Dna repair activity in children exposed to small doses of ionizing radiation as
      a result of the accident at the Chernobyl nuclear power station].
AB  - The repair activity of DNA was studied by variola vaccine virus reactivation and
      induced mutagenesis tests in the peripheral blood lymphocytes of children living
      in areas with an increased level of ionizing radiation due to breakdown at the
      Chernobyl' nuclear power station. A more profound repair disturbance was revealed
      in children living on strictly controlled territories and born after the
      disaster, compared to those born before it, and children living in areas where
      the radiation level does not exceed background values. The disturbances were
      characterized by increased induced mutagenesis and decreased reactivation of the
      variola vaccine virus. No changes in the degree of DNA repair synthesis were
      registered in any of the groups studied.

PMID- 8543146
TI  - [Dominant monogenic markers of quantitative characters].
AB  - Peculiarities of interdependent variation of monogenic and polygenic traits were
      analyzed using a one-locus diallelic model of a monogenic, dominantly inherited
      trait. The possibility of determining the mean genotypic value of the trait (m)
      and also the additive (a) and nonadditive (d) effects of the interaction between
      alleles of a monogenic trait on a quantitative trait is considered. It is shown
      that a and d can differ from zero even if the mean values in the groups with
      dominant and recessive phenotypes are equal. Equations are presented that allow
      the direct use of data obtained in population studies for determining m, a, and
      d, as well as corresponding standard errors under the conditions of codominance
      and dominance of the monogenic trait. Another group of equations allows
      determination of the sample size necessary for calculating m, a, and d. The
      problem concerning the ambiguity of m, a, and d values calculated using the
      proposed equations is discussed. This ambiguity depends on the fact that
      identification of genotypes in the case of a dominantly inherited monogenic trait
      is impossible.

PMID- 8543147
TI  - [A simple method for detecting the order of relation location of fragments in
      constructing a paired restriction map].
AB  - A simple method for the ordering of fragments and the determination of relative
      positions of restriction sites when constructing pair restriction maps of linear
      and circular DNAs is described. The major advantages of the suggested approach as
      compared to the routine strategy of exhaustive search are as follows: (1) One
      does not need to begin the construction of the map by searching for the
      restrictases that produce the least number of fragments; (2) the method allows
      one to construct quite complicated maps, the main limiting parameter being the
      number of fragments during double digestion (no more than 10-12); and (3)
      construction of the map using this approach is less labor- and time-consuming
      than the routine strategy.

PMID- 8543148
TI  - [Relationship between amplicon composition and cytologic type of structures
      containing amplified DNA in murine P388 cells with multiple drug resistance].
AB  - Previously, we showed that, development of multidrug resistance (MDR) in mouse
      P388 leukemia cells, is often associated with the appearance of newly-formed
      chromosome-like structures that contain amplified copies of the mdrl gene. In the
      present study, we compared amplicon content in P388 sublines showing different
      types of these structures. A strong correlation between the formation of specific
      acentric markers consisting of two identical arms and the absence of the sorcin
      gene co-amplification was found. In all the sublines containing other types of
      chromosome-like structures, the sorcin gene is co-amplified.

PMID- 8543150
TI  - Molecular mechanisms of Spemann's organizer formation: conserved growth factor
      synergy between Xenopus and mouse.
AB  - Mesoderm induction assays in Xenopus have implicated growth factors such as
      activin, Vg1, Xwnt-8, and noggin as important in directing the formation of
      dorsal mesoderm (Spemann's organizer). Because these growth factors are
      structurally very different, they presumably act through distinct cell surface
      receptors that initiate different intracellular signaling cascades. A consequence
      of all of these signaling pathways, however, seems to be the induction of
      goosecoid (gsc) gene expression. To understand how integration of these different
      signaling pathways results in formation of Spemann's organizer, we sought to
      identify growth factor-responsive elements within the gsc promoter. Through
      microinjection of reporter genes we have identified two cis-acting elements, a
      distal element (DE) and a proximal element (PE), that are required for
      activin/BVg1 and Wnt induction, respectively. We have shown that the DE mediates
      activin induction in the absence of protein synthesis and therefore constitutes
      the first activin response element identified to interpret transforming growth
      factor-beta (TGF-beta) superfamily member signaling directly. Using a reporter
      gene construct containing a multimerized DE, we find that an activin/BVg1-type
      signaling cascade is active throughout the vegetal hemisphere and marginal zone
      but not in the animal hemisphere. We demonstrate further that both the distal and
      proximal elements are essential for high-level transcription of the gsc gene,
      specifically in dorsal mesoderm, strongly suggesting that establishment of
      Spemann's organizer requires synergistic input from activin/BVg1-like and Wnt
      signaling pathways. Finally, mechanisms of establishing the organizer are likely
      to be conserved throughout vertebrate evolution.

PMID- 8543149
TI  - Bmpr encodes a type I bone morphogenetic protein receptor that is essential for
      gastrulation during mouse embryogenesis.
AB  - Bone morphogenetic proteins (BMPs) are secreted proteins that interact with cell
      surface receptors and are believed to play a variety of important roles during
      vertebrate embryogenesis. Bmpr, also known as ALK-3 and Brk-1, encodes a type I
      transforming growth factor-beta (TGF-beta) family receptor for BMP-2 and BMP-4.
      Bmpr is expressed ubiquitously during early mouse embryogenesis and in most adult
      mouse tissues. To study the function of Bmpr during mammalian development, we
      generated Bmpr-mutant mice. After embryonic day 9.5 (E9.5), no homozygous mutants
      were recovered from heterozygote matings. Homozygous mutants with morphological
      defects were first detected at E7.0 and were smaller than normal. Morphological
      and molecular examination demonstrated that no mesoderm had formed in the mutant
      embryos. The growth characteristics of homozygous mutant blastocysts cultured in
      vitro were indistinguishable from those of controls; however, embryonic ectoderm
      (epiblast) cell proliferation was reduced in all homozygous mutants at E6.5
      before morphological abnormalities had become prominent. Teratomas arising from
      E7.0 mutant embryos contained derivatives from all three germ layers but were
      smaller and gave rise to fewer mesodermal cell types, such as muscle and
      cartilage, than controls. These results suggest that signaling through this type
      I BMP-2/4 receptor is not necessary for preimplantation or for initial
      postimplantation development but may be essential for the inductive events that
      lead to the formation of mesoderm during gastrulation and later for the
      differentiation of a subset of mesodermal cell types.

PMID- 8543151
TI  - A proline-rich TGF-beta-responsive transcriptional activator interacts with
      histone H3.
AB  - The molecular mechanisms involved in the regulation of gene expression by
      transforming growth factor-beta (TGF-beta) have been analyzed. We show that TGF
      beta specifically induces the activity of the proline-rich trans-activation
      domain of CTF-1, a member of the CTF/NF-I family of transcription factors. A TGF
      beta-responsive domain (TRD) in the proline-rich transcriptional activation
      sequence of CTF-1 was shown to mediate TGF-beta induction in NIH-3T3 cells.
      Mutagenesis studies indicated that this domain is not the primary target of
      regulatory phosphorylations, suggesting that the growth factor may regulate a CTF
      1-interacting protein. A two-hybrid screening assay identified a nucleosome
      component, histone H3, as a specific CTF-1-interacting protein in yeast.
      Furthermore, the CTF-1 trans-activation domain was shown to interact with histone
      H3 in both transiently and stably transfected mammalian cells. This interaction
      requires the TRD, and it appears to be upregulated by TGF-beta in vivo. Moreover,
      point mutations in the TRD that inhibit TGF-beta induction also reduce
      interaction with histone H3. In vitro, the trans-activation domain of CTF-1
      specifically contacts histone H3 and oligomers of histones H3 and H4, and full
      length CTF-1 was shown to alter the interaction of reconstituted nucleosomal
      cores with DNA. Thus, the growth factor-regulated trans-activation domain of CTF
      1 can interact with chromatin components through histone H3. These findings
      suggest that such interactions may regulate chromatin dynamics in response to
      growth factor signaling.

PMID- 8543152
TI  - The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a
      B cell-specific trans-activator that describes a new DNA-binding protein family.
AB  - B lymphocyte-restricted transcription of immunoglobulin heavy-chain (IgH) genes
      is specified by elements within the variable region (VH) promoter and the
      intronic enhancer (E mu). The gene encoding a protein that binds a VH promoter
      proximal site necessary for induced mu-heavy-chain transcription has been cloned.
      This B-cell specific protein, termed Bright (B cell regulator of IgH
      transcription), is found in both soluble and matrix insoluble nuclear fractions.
      Bright binds the minor groove of a restricted ATC sequence that is sufficient for
      nuclear matrix association. This sequence motif is present in previously
      described matrix-associating regions (MARs) proximal to the promoter and flanking
      E mu. Bright can activate E mu-driven transcription by binding these sites, but
      only when they occur in their natural context and in cell lines permissive for E
      mu activity. To bind DNA, Bright requires a novel tetramerization domain and a
      previously undescribed domain that shares identity with several proteins,
      including SWI1, a component of the SWI/SNF complex.

PMID- 8543153
TI  - Synergistic regulation of human beta-globin gene switching by locus control
      region elements HS3 and HS4.
AB  - Proper tissue- and developmental stage-specific transcriptional control over the
      five genes of the human beta-globin locus is elicited in part by the locus
      control region (LCR), but the molecular mechanisms that dictate this determined
      pattern of gene expression during human development are still controversial. By
      use of homologous recombination in yeast to generate mutations in the LCR within
      a yeast artificial chromosome (YAC) bearing the entire human beta-globin gene
      locus, followed by injection of each of the mutated YACs into murine ova, we
      addressed the function of LCR hypersensitive site (HS) elements 3 and 4 in human
      beta-globin gene switching. The experiments revealed a number of unexpected
      properties that are directly attributable to LCR function. First, deletion of
      either HS3 or HS4 core elements from an otherwise intact YAC results in
      catastrophic disruption of globin gene expression at all erythroid developmental
      stages, despite the presence of all other HS elements in the YAC transgenes. If
      HS3 is used to replace HS4, gene expression is normal at all developmental
      stages. Conversely, insertion of the HS4 element in place of HS3 results in
      significant expression changes at every developmental stage, indicating that
      individual LCR HS elements play distinct roles in stage-specific beta-type globin
      gene activation. Although the HS4 duplication leads to alteration in the levels
      of epsilon- and gamma-globin mRNAs during embryonic erythropoiesis, total beta
      type globin mRNA synthesis is balanced, thereby leading to the conclusion that
      all of the human beta-locus genes are competitively regulated. In summary, the
      human beta-globin HS elements appear to form a single, synergistic functional
      entity called the LCR, and HS3 and HS4 appear to be individually indispensable to
      the integrity of this macromolecular complex.

PMID- 8543154
TI  - Allele-specific expression and total expression levels of imprinted genes during
      early mouse development: implications for imprinting mechanisms.
AB  - Genomic imprinting determines the monoallelic expression of a small number of
      genes during at least later stages of development. To obtain information
      necessary for the elucidation of imprinting mechanisms, we assessed the allele
      specific expression and total expression level of four imprinted genes during
      early stages of development of normal F1 hybrid mice utilizing quantitative
      allele-specific reverse transcription-PCR (RT-PCR) single-nucleotide primer
      extension assays. The Igf2r and Snrpn genes were activated by the early 4-cell
      stage and exhibited biallelic and monoallelic expression, respectively,
      throughout preimplantation development. Thus, with respect to different imprinted
      genes, epigenetic systems determining monoallelic expression are not uniform in
      their time of establishment. Biallelic expression of Igf2r was observed in single
      blastomeres, discounting the possibility of random allelic inactivation at this
      stage. The closely linked H19 and Igf2 genes were activated after the blastocyst
      stage and often exhibited biallelic and monoallelic expression respectively in
      tissues of pregastrulation postimplantation-stage embryos, rather than reciprocal
      monoallelic modes as observed at later stages. This raises the possibility that
      imprinting of H19 is involved only in the maintenance and not in the initiation
      of monoallelic expression of Igf2. Monoallelic expression of Snrpn was observed
      in each blastomere at the 4-cell stage, demonstrating that the germ line, which
      exhibits biallelic expression of imprinted genes, must be derived from cells in
      which imprinting was once manifest.

PMID- 8543155
TI  - The POU domain transcription factor Brn-2 is required for the determination of
      specific neuronal lineages in the hypothalamus of the mouse.
AB  - We generated mice carrying a loss-of-function mutation in Brn-2, a gene encoding
      a nervous system specific POU transcription factor, by gene targeting in
      embryonic stem cells. In homozygous mutant embryos, migratory precursor cells for
      neurons of the paraventricular nuclei (PVN) and the supraoptic nuclei (SO) of the
      hypothalamus die at approximately E12.5. All homozygous mutants suffered
      mortality within 10 days after birth, possibly because of a complete deficiency
      of these neurons in the hypothalamus. Although neither developmental nor
      histological abnormalities were observed in heterozygous mice, the levels of
      expression of vasopressin and oxytocin in the hypothalamus of these animals were
      half these of wild-type mice. These results strongly suggest that Brn-2 plays an
      essential role in the determination and development of the PVN and SO neuronal
      lineages in the hypothalamus.

PMID- 8543156
TI  - Development and survival of the endocrine hypothalamus and posterior pituitary
      gland requires the neuronal POU domain factor Brn-2.
AB  - Neurons comprising the endocrine hypothalamus are disposed in several nuclei that
      develop in tandem with their ultimate target the pituitary gland, and arise from
      a primordium in which three related class III POU domain factors, Brn-2, Brn-4,
      and Brn-1, are initially coexpressed. Subsequently, these factors exhibit
      stratified patterns of ontogenic expression, correlating with the appearance of
      distinct neuropeptides that define three major endocrine hypothalamic cell types.
      Strikingly, deletion of the Brn-2 genomic locus results in loss of endocrine
      hypothalamic nuclei and the posterior pituitary gland. Lack of Brn-2 does not
      affect initial hypothalamic developmental events, but instead results in a
      failure of differentiation to mature neurosecretory neurons of the
      paraventricular and supraoptic nuclei, characterized by an inability to activate
      genes encoding regulatory neuropeptides or to make correct axonal projections,
      with subsequent loss of these neurons. Thus, both neuronal and endocrine
      components of the hypothalamic-pituitary axis are critically dependent on the
      action of specific POU domain factors at a penultimate step in the sequential
      events that underlie the appearance of mature cellular phenotypes.

PMID- 8543157
TI  - Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1)
      leads to up-regulation of neural helix-loop-helix factors, premature
      neurogenesis, and severe neural tube defects.
AB  - Mammalian hairy and Enhancer of split homolog-1 (HES-1) encodes a helix-loop
      helix (HLH) factor that is thought to act as a negative regulator of
      neurogenesis. To directly investigate the functions of HES-1 in mammalian
      embryogenesis, we performed a targeted disruption of the HES-1 locus. Mice
      homozygous for the mutation exhibited severe neurulation defects and died during
      gestation or just after birth. In the developing brain of HES-1-null embryos,
      expression of the neural differentiation factor Mash-1 and other neural HLH
      factors was up-regulated and postmitotic neurons appeared prematurely. These
      results suggest that HES-1 normally controls the proper timing of neurogenesis
      and regulates neural tube morphogenesis.

PMID- 8543158
TI  - The Caenorhabditis elegans gene lin-1 encodes an ETS-domain protein and defines a
      branch of the vulval induction pathway.
AB  - The Caenorhabditis elegans gene lin-1 appears to act after the Ras-Raf-MEK-MAPK
      signaling cascade that mediates vulval induction. We show that lin-1 is a
      negative regulator of vulval cell fates and encodes an ETS-domain putative
      transcription factor containing potential MAPK phosphorylation sites. In lin-1
      null mutants, the vulval precursor cells (VPCs) still respond to signaling from
      the gonadal anchor cell, indicating that lin-1 defines a branch of the inductive
      signaling pathway. We also provide evidence that the inductive and lateral
      signaling pathways are integrated to control the 1 degree and 2 degrees vulval
      cell fates after the point at which lin-1 acts in the inductive pathway and that
      VPCs can assess the relative rather than absolute levels of inductive and lateral
      signaling in determining whether to express the 1 degree or 2 degrees vulval cell
      fates.

PMID- 8543159
TI  - The torso response element binds GAGA and NTF-1/Elf-1, and regulates tailless by
      relief of repression.
AB  - Modulation of transcription factor activity leading to changes in cell behavior
      (e.g., differentiation versus proliferation) is one of the critical outcomes of
      receptor tyrosine kinase (RTK) stimulation. In the early Drosophila embryo,
      activation of the torso (tor) RTK at the poles of the embryo activates a
      phosphorylation cascade that leads to the spatially specific transcription of the
      tailless (tll) gene. Our analysis of the tor response element (tor-RE) in the tll
      promoter indicates that the key activity modulated by the tor RTK pathway is a
      repressor present throughout the embryo. We have mapped the tor-RE to an 11-bp
      sequence; using this sequence as the basis for protein purification, we have
      determined that the proteins GAGA and NTF-1 (also known as Elf-1, product of the
      grainyhead gene) bind to the tor-RE. We demonstrate that NTF-1 can be
      phosphorylated by MAPK (mitogen-activated protein kinase), and that tll
      expression is expanded in embryos lacking maternal NTF-1 activity; these results
      make NTF-1 a likely target for modulation by the tor RTK pathway in vivo. The
      data presented here support a model in which activation of the tor RTK at the
      poles of the embryos leads to inactivation of the repressor and therefore, to
      transcriptional activation (by activators present throughout the embryo) of the
      tll gene at the poles of the embryo.

PMID- 8543160
TI  - Binding sites for transcription factor NTF-1/Elf-1 contribute to the ventral
      repression of decapentaplegic.
AB  - The Dorsal morphogen is a transcription factor that activates some genes and
      represses others to establish multiple domains of gene expression along the
      dorsal/ventral axis of the early Drosophila embryo. Repression by Dorsal appears
      to require accessory proteins that bind to corepression elements in Dorsal
      dependent regulatory modules called ventral repression regions (VRRs). We have
      identified a corepression element in decapentaplegic (dpp), a zygotically active
      gene that is repressed by the Dorsal morphogen. This dpp repression element (DRE)
      is located within a previously identified VRR and close to essential Dorsal
      binding sites. We have purified a factor from Drosophila embryo extracts that
      binds to the DRE but not to mutant forms of the DRE that fail to support
      efficient repression. This protein also binds to an apparently essential region
      in a VRR associated with the zerknullt (zen) gene. One of the DREs in the dpp VRR
      overlaps the binding site for a potential activator protein suggesting that one
      mechanism of ventral repression may be the mutually exclusive binding of
      repressor and activator proteins. We have found the DRE-binding protein to be
      identical to NTF-1 (equivalent to Elf-1, the product of the grainyhead gene), a
      factor originally identified as an activator of the Ultrabithorax and Dopa
      decarboxylase promoters. NTF-1 mRNA is synthesized during oogenesis and deposited
      in the developing oocyte where it is available to contribute to ventral
      repression during early embryogenesis. Previous studies have shown that
      overexpression of NTF-1 in the postblastoderm embryo results in a phenotype that
      is consistent with a role for this factor in the repression of dpp later in
      embryogenesis.

PMID- 8543161
TI  - Epitope mapping of anti-HIV and anti-HCV monoclonal antibodies and
      characterization of epitope mimics using a filamentous phage peptide library.
AB  - A large filamentous phage library (1 x 10(9) clones) displaying random 30-amino
      acid (aa) sequences on the N terminus of the pIII coat protein was constructed
      and characterized. Clones in the library were affinity selected for binding to
      monoclonal antibodies (mAb) against two viral antigens, the HIV gp120 protein and
      the HCV core protein. The obtained aa sequences precisely identified the epitopes
      recognized by the mAb. Binding of peptide-carrying phages to the Ab was
      demonstrated by ELISA, Western blot and the surface plasmon resonance (SPR)
      method. The mAb-specific peptides were transferred via genetic techniques onto
      the N terminus of Escherichia coli alkaline phosphatase (AP). When fused to the
      enzyme, the peptides maintained their ability to bind their respective mAb,
      indicating that the peptides contained the necessary contact residues for
      binding. The affinity of the peptides was estimated to be 100 nM by SPR. A
      comparison is presented of the relative affinities of phage-derived peptides to
      the native viral epitopes also displayed on the AP scaffold. The approach of
      transferring epitopes from phage to AP for further evaluation should be
      applicable to many other mAb or receptors.

PMID- 8543162
TI  - A replacement vector used to introduce subtle mutations into mouse genes.
AB  - A replacement vector convenient for introducing subtle mutations into various
      mouse genes has been developed using, a model system, the mouse transthyretin
      encoding gene (ttr) and mouse embryonal carcinoma F9 cells. The vector consists
      of part of ttr carrying a subtle mutation in its second exon, and a cassette of
      the neomycin-resistance (neo)- and herpes simplex virus thymidine kinase (HSV-tk)
      encoding genes flanked with a 3-kb duplication of mostly the second intron of
      ttr. In the first step ('replacement'), part of the endogenous ttr was replaced
      by vector DNA via homologous recombination, and two such clones, #33 and #77,
      were isolated from 185 G418-resistant clones by allele-specific PCR. In the
      second step ('excision'), gancyclovir-resistant colonies were screened, and 7 and
      84% of those isolated from clones #33 and #77, respectively, were demonstrated to
      carry the subtle mutation in ttr, without the cassette of selection markers. In
      five independently isolated random integrants of the same vector DNA, the
      cassette of selection markers was excised efficiently by recombination within the
      duplication.

PMID- 8543163
TI  - Isolation and characterization of a cDNA encoding the alpha' subunit of human
      cone cGMP-phosphodiesterase.
AB  - A human cDNA (alpha-PDE) encoding the alpha' catalytic subunit of cone
      photoreceptor cGMP-phosphodiesterase has been isolated and characterized. The
      nucleotide sequence of 2980 bp contains an open reading frame encoding an 859
      amino-acid (aa) protein with a calculated molecular mass of 99 kDa. Northern blot
      analysis of human retinal mRNA hybridized with the alpha'-PDE cDNA revealed a
      signal corresponding to a 3.2-kb transcript. Comparison of the deduced aa
      sequence of human cone alpha'-PDE with corresponding proteins isolated from
      bovine and chicken retinas shows 89 and 83% identity, respectively, and indicates
      that alpha'-PDE has been very well conserved in the evolutionary process. Human
      cone alpha'-PDE is highly homologous to rod alpha-PDE and beta-PDE, suggesting
      that these proteins may have a close phylogenetic relationship.

PMID- 8543164
TI  - Cloning of putative growth regulatory genes from primary human keratinocytes by
      subtractive hybridization.
AB  - In order to isolate genes that might be involved in regulating human keratinocyte
      (HKc) growth and/or differentiation, we constructed a cDNA library by subtractive
      hybridization between primary HKc and FaDu head-and-neck squamous cell carcinoma
      cells. Among the first set of independent cDNAs that we have isolated, ten
      correspond to known genes, and two represent novel sequences. Nine of the ten
      known genes are expressed at significantly lower levels in the majority of the
      SqCC cell lines in comparison with primary HKc. These include cDNAs that encode
      keratins K5 and K14 which are cytoskeletal proteins normally expressed in lining
      epithelia, the 14-3-3 protein stratifin/HME-1, lipocortin-II and CaN19 which are
      calcium-binding proteins that may play a role in HKc differentiation by
      regulating protein kinase C, plasminogen-activator inhibitor-2 which is a serine
      proteinase inhibitor, HBp17 which is a HKc-specific secreted inhibitor of
      fibroblast growth factors, integrin alpha 3 which plays a role in the anchoring
      of keratinocytes to basement membrane, and YL-8, a ras-like protein that probably
      mediates intracellular protein trafficking. In addition, we isolated two cDNAs,
      LIS-1 which encodes the 45-kDa intracellular subunit of the platelet-activating
      factor acetyl-hydrolase, and the unknown sequence HFBCB84 which showed reduced
      expression in only a small number of tumor lines as compared to HKc. Inactivation
      or loss of any of these proteins may confer a selective advantage onto squamous
      epithelial cells and contribute to their malignant transformation.

PMID- 8543165
TI  - Integration of an Epstein-Barr virus episome 3' into the gene encoding
      immunoglobulin heavy-chain alpha 1 in a lymphoblastoid cell line.
AB  - For the first time we have characterized an unoccupied site of Epstein-Barr (EBV)
      virus integration in a lymphoblastoid cell line, RGN1. The site of integration is
      about 1.5 kb downstream from the gene encoding the heavy chain constant alpha 1,
      specifying immunoglobulin A (IgA). Sequence and Southern analysis allowed us to
      hypothesize that integration occurred via a double exchange involving the viral
      latent origin of DNA replication (oriP) and the human DNA. The region involved in
      the integration is transcribed into poly(A)+ RNA in all the tested lymphoid
      lines, but not in the RGN1 line. We suggest a mechanism of integration primed by
      interactions between oriP and cell ori and its potential role in the
      establishment and/or evolution of EBV-carrying lines.

PMID- 8543166
TI  - Antiviral activity and protection of cells against human immunodeficiency virus
      type-1 using an antisense oligodeoxyribonucleotide phosphorothioate complementary
      to the 5'-LTR region of the viral genome.
AB  - A COS-like monkey kidney cell line stably transfected with the plasmids
      pCMVgagpol-rre-r with the gag and pol genes, and pCMV rev with the rev gene of
      HIV-1 derived from the cDNA clone BH10, was used as a model for assessing the
      effectiveness of antisense (AS) constructs, A 20-mer oligodeoxyribonucleotide
      (oligo) phosphorothioate sequence (5'-CCG CCC CTC GCC TCT TGC CG) complementary
      to a portion of the 5'-long terminal repeat (5'-LTR) of the HIV-1 genome was
      tested for its inhibitory effects on the biologically important processes of HIV
      1 replication and proliferation. We observed a concentration-dependent inhibition
      of HIV protein synthesis. Desitometric analysis of data from Western blot
      analysis showed sequence-specific and concentration-dependent oligo inhibition of
      p24 viral core antigen formation in the low-microM range. When lipofectin was
      used as a delivery vehicle, a markedly increased potentiation of the AS activity
      of the sequence was observed at a lower concentration (0.1 microM), following a
      24-h preincubation. The AS construct specifically inhibited intracellular p24
      production in chronically HIV-1-infected cells of lymphoid origin (H9/IIIB cells)
      by 95%, resulting in a 15-fold inhibitory effect relative to a similar sequence
      thiolated at only seven single-base positions. A concentration-dependent
      attenuation in the reverse transcriptase activity and a reduction in viral p24
      level was observed in the culture supernatant of AS-pretreated HIV-1-infected
      phytohemagglutinin A-stimulated human cord blood mononuclear cells. Incubation of
      a HIV-1-infected lymphoid cell line with AS sequence resulted in a marked
      reduction in syncytium formation, and therefore protected cells from the
      cytopathic effects of the virus. Furthermore, the AS oligo did not appear to be
      cytotoxic in cell growth rate and colony-forming ability assays. The AS oligo
      described in this report is a useful new tool for the molecular analysis of HIV-1
      gene expression and proliferation, and may have potential as a therapeutic agent.

PMID- 8543167
TI  - The DRE sequence TATCGATA, a putative promoter-activating element for Drosophila
      melanogaster cell-proliferation-related genes.
AB  - We have confirmed that the DNA replication-related element (DRE) consisting of an
      8-bp palindrome, TATCGATA, and not neighboring sequences, are responsible for
      activating promoters of the Drosophila melanogaster (Dm) PCNA (proliferating cell
      nuclear antigen)- and DNA polymerase alpha-encoding genes in both cultured cell
      and transgenic fly systems. We have so far found 153 copies of DRE in the Dm gene
      database. 73 of them are concentrated within the 600-bp upstream regions from the
      transcription start points of 61 genes. Interestingly, many of these genes are
      involved in either DNA replication, transcription, translation, signal
      transduction, cell cycle or other putative regulatory functions, and are possibly
      related to cell proliferation. It seems likely that DRE is an element common to
      the regulation of cell-proliferation-related genes, although their expression
      patterns may be different depending on which of regulatory elements other than
      the DRE are combined.

PMID- 8543168
TI  - Isolation and sequence determination of the cDNA encoding DNA polymerase delta
      from Drosophila melanogaster.
AB  - The cDNA encoding the catalytic subunit of Drosophila melanogaster (Dm) DNA
      polymerase delta (Pol delta) was isolated by a combination of PCR amplification
      and cDNA library screening. The cDNA is 3457 nucleotides in length and contains
      an open reading frame (ORF) that encodes a protein of 1092 amino acids (124,799
      Da). The ORF contains the sequence that was determined for a peptide from the
      purified catalytic subunit of Dm Pol delta. Polyclonal antibodies raised against
      Dm Pol delta specifically recognize a protein of the expected size when the cDNA
      is expressed in either Escherichia coli or insect cells. Comparison of the
      deduced aa sequence with other Pol delta sequences demonstrates that Pol delta is
      one of the most highly conserved of the DNA polymerases.

PMID- 8543169
TI  - Characterization of the transcription start point of the trout estrogen receptor
      encoding gene: evidence for alternative splicing in the 5' untranslated region.
AB  - The estrogen receptor (ER)-encoding gene (ER) regulates many genes implicated in
      the reproductive functions. Moreover, rainbow trout ER (rtER) is itself up
      regulated by its own product. We have used Northern blot, RNase protection,
      primer extension and reverse transcription-polymerase chain reaction (RT-PCR) to
      study the position of the rtER mRNA transcription start point (tsp) in liver.
      This analysis has revealed the presence of a tsp positioned at the beginning of
      the cloned rtER cDNA. Functionality of this tsp was tested in transient
      transfections in CHO-K1 cells. The characterization of the rtER 5' untranslated
      region (UTR) showed that two transcripts exist in liver which differ in their 5'
      UTR. The first one is 100% homologous to the cloned rtER cDNA sequence. The other
      one contains a 41-bp insertion. The isolation and sequencing of the first intron
      showed that this insertion arises from alternative splicing, due to the use of a
      splicing site internal to the first intron.

PMID- 8543170
TI  - Cloning and sequencing of the chaperonin-encoding Cctd gene from Fugu rubripes
      rubripes.
AB  - CCT, a chaperonin containing t-complex polypeptide 1 (TCP-1), is a cytosolic
      molecular chaperone involved in the folding of proteins. We have isolated the
      Cctd gene from a Fugu rubripes rubripes (Frr) genomic library using a rat Ccta
      cDNA as a probe, and cloned its cDNA by reverse transcription-polymerase chain
      reaction (RT-PCR) using a pair of oligodeoxyribonucleotides corresponding to the
      5' and 3' non-coding regions of Frr Cctd. Cctd spans a region of 4.7 kb and
      consists of at least 13 exons with small introns of about 144 bp on average. The
      Cctd cDNA sequence revealed a deduced polypeptide of 536 amino acids sharing a
      high degree of homology with that of the mouse Cctd cDNA (88%). Cctd is present
      as a single-copy gene, as shown by genomic Southern blot analysis, and can be
      used for evolutionary and classification analyses of Fugu species.

PMID- 8543171
TI  - Analysis of the replication direction through the domain of alpha-globin-encoding
      chicken genes.
AB  - The polarity of leading DNA strand synthesis through the domain of alpha-globin
      encoding genes in chicken erythroid cells has been studied using a modification
      of the previously published replication direction assay [Handeli et al., Cell 57
      (1989) 909-920; Burhans et al., EMBO J. 10 (1991) 4351-4360]. In accordance with
      our previous observations [Razin et al., Nucleic Acids Res. 14 (1986) 8189-8207],
      it has been found that a replication origin (ori) is located in the area
      extending from 8.5 to 2.5 kb upstream from the pi gene, the first gene of the
      domain. The whole domain is replicated from this ori in the direction of
      transcription. The replication termination site has been mapped right after the
      last gene of the domain (alpha A gene) at a distance of about 12 kb from the ori.

PMID- 8543172
TI  - Structure and regulation of the gene encoding avian inhibitor of nuclear factor
      kappa B-alpha.
AB  - The Rel/NF-kappa B family of transcription factors exist in the cytoplasm as
      inactive complexes in association with an inhibitory protein called I kappa B
      alpha. We have isolated a clone containing the avian I kappa B-alpha gene from a
      chicken genomic library. Avian I kappa B-alpha is devoid of any recognizable
      promoter elements, i.e., TATA and CAAT boxes; however, the 5'-UTR of the gene
      contains the initiator elements frequently found in TATA-less genes. Avian I
      kappa B-alpha contains seven putative Rel/NF-kappa B binding sites. A CAT
      reporter construct containing the 5' upstream region of I kappa B-alpha was
      expressed when transfected into cells which produce I kappa B-alpha. This
      construct, however, was not expressed in cells in which I kappa B-alpha activity
      was not induced, indicating that the regulatory elements which promote I kappa B
      alpha expression are contained within 1000 nt of the transcription start site.
      Southern analysis suggests that I kappa B-alpha is present as a single-copy gene
      per haploid genome and is expressed in avian hematopoietic tissues, as well as
      lymphoid cells transformed by avian reticuloendotheliosis virus (REV-T).

PMID- 8543173
TI  - Promoter region of the mouse cyclin-dependent kinase 5-encoding gene.
AB  - While cyclin-dependent kinases, such as CDC2 and CDK2, are key regulators of cell
      cycle progression, cyclin-dependent kinase 5 (CDK5) is highly expressed in mature
      neurons with no evident cell-cycle regulation. The 5'-region of the mouse CDK5
      gene was isolated and sequenced. The isolated clone included exons 1 through 7.
      The 5'-flanking region has a high G+C content. There is no TATA box around the
      transcriptional start points (tsp), as determined by primer extension analysis.
      One CCAAT box, one AP-1-binding site, two AP-2-binding sites, and one cAMP
      responsive element are located upstream from the tsp. Promoter/cat fusion assays
      showed that the 5.8-kb fragment of this 5'-flanking sequence possessed the
      promoter activities expressing cat in rat PC12 pheochromocytoma cells. The effect
      of deletions of the promoter suggested the presence of two negative control
      elements located from -2.9 kb to -546 bp, and from -212 to -155 upstream from the
      5' end of the tsp. Two positive elements from bp -300 to -212 and from -155 to 
      41 were also detected. In the element from bp -300 to -212, there was a putative
      NF-IL6-binding sequence. Thus, the CDK5 promoter region contains multiple
      positive and negative cis-acting regulatory elements, an arrangement which
      suggests that the regulation of transcription of CDK5 is under complex control.

PMID- 8543174
TI  - A COS-cell-based system for rapid production and quantification of scFv::IgC
      kappa antibody fragments.
AB  - Single-chain Fv (scFv) antibody (Ab) fragments were transiently produced in COS-1
      cells utilizing a mammalian expression vector featuring a murine immunoglobulin
      (Ig) light-chain leader sequence for efficient secretion and a murine Ig kappa
      constant domain (IgC kappa) for detection. Several hundred milliliters of
      supernatants from large-scale COS cell transfections were sufficient to purify
      the scFv::IgC kappa fusion proteins by one-step affinity chromatography utilizing
      an immobilized rat anti-mouse IgC kappa monoclonal Ab. Furthermore, the murine
      IgC kappa domain allowed for accurate quantification of the scFv::IgC kappa
      fusion protein secreted into the COS cell supernatant by a sandwich enzyme-linked
      immunosorbent assay (S-ELISA).

PMID- 8543175
TI  - Structural organization and expression of the mouse gene encoding alpha
      galactosidase A.
AB  - alpha-Galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22; alpha
      GalA) is a lysosomal enzyme that hydrolyses the alpha-D-galactosyl residues from
      glycosphingolipids. Fabry disease, an inhibited X-linked recessive human
      metabolic disorder, results from a mutation in the alpha GalA gene at Xq22. As a
      prerequisite for generating a mouse model of Fabry disease by gene targeting, we
      have isolated and characterized the mouse alpha GalA gene and cDNA. A cloned
      mouse alpha GalA cDNA encoded a putative precursor protein of 419 amino acids
      (aa), including a 31-aa signal peptide (SP). The deduced aa sequence showed high
      homology (79%) with the human alpha GalA protein. Nucleotide sequence analysis of
      genomic clones revealed that the overall structure and organization of the gene
      was very similar to that of human alpha GalA. All exon-intron splice junctions
      conformed to the GT/AG consensus sequence. Comparison of genomic and cDNA
      sequences revealed the occurrence of two putative polyadenylation signals whose
      alternative use results in the two mouse alpha GalA transcripts of 1.4 and 3.6
      kb. The 5'-flanking region of mouse alpha GalA had no typical TATA box. Several
      putative promoter-associated elements including Sp1, AP1 and a potential cAMP
      responsive element (CRE) were identified. Northern blot analysis revealed the
      widespread tissue distribution of mouse alpha GalA transcripts. Lower expression
      levels, however, were observed in some tissues, implying tissue-specific
      differences in alpha GalA promoter function.

PMID- 8543176
TI  - Transcriptional regulation of the vimentin-encoding gene in mouse myeloid
      leukemia M1 cells.
AB  - To investigate the regulatory mechanisms controlling expression of the vimentin
      encoding gene (Vim) during mouse myeloid leukemia M1 cell differentiation, mouse
      Vim was cloned and the transcriptional activity of its 5' promoter region was
      analysed by chloramphenicol acetyltransferase (CAT) assay. Analyses of various
      deletion mutants revealed that a 188-bp fragment of the proximal Vim promoter
      (pVim) was sufficient for effective transcription in M1 cells. This 188-bp
      sequence is highly conserved between mouse, hamster and human. Further deletion
      analyses revealed that a minimum promoter element (-44 to +26) is essential for
      basic promoter function and could respond to cell differentiation. Detailed
      analyses of mutant and chimeric pVim constructs defined a CCAAT box at -89 to -84
      to be an essential positive regulatory element. A G+C-rich element between the
      CCAAT and TATA boxes was found to act as a strong negative regulatory element in
      Vim transcription.

PMID- 8543177
TI  - Sequence, initial functional analysis and protein-DNA binding sites of the mouse
      beta B2-crystallin-encoding gene.
AB  - An 800-bp fragment of genomic DNA upstream from the origin of transcription of
      the mouse beta B2-crystallin-encoding gene (beta B2-Cry) has been isolated and
      its nucleotide sequence determined. Promoter fragments 275 to +30 or -110 to +30,
      fused to cat reporter gene, activated transcription in transiently transfected
      rabbit lens epithelial cells, but not in various non-lens cells. The beta B2-Cry
      mouse promoter contains a typical TATA-box located approx. 25 bp upstream from
      the transcription start point. Binding sites (upstream from the TATA-box) for
      transcription factors possibly involved in the regulation of gene expression have
      been identified by DNaseI footprinting analysis and lens cell nuclear extracts.
      Most notably is the binding of the Pax-6 paired domain (PrD) which correlates
      with the binding of lens cell nuclear proteins at the -80 to -40 region.

PMID- 8543178
TI  - Cloning and expression of a murine cDNA homologous to the human RCK/P54, a
      lymphoma-linked chromosomal translocation junction gene on 11q23.
AB  - The RCK/P54 gene was previously isolated from the chromosome translocation
      breakpoint region on 11q23 of a human lymphoma cell line, RC-K8, with
      t(11;14)(q23;q32). It was found to encode a 472-483-amino-acid (aa) polypeptide
      belonging to an RNA helicase/translation initiation factor family. The aim of the
      present investigation was the isolation and comparative sequence analysis of the
      mouse RCK/P54 cDNA from a BALB/c spleen cDNA library. Sequence analysis revealed
      an open reading frame (ORF) predicting a polypeptide of 483 aa showing 97.7%
      identity to human RCK/p54. Northern analysis demonstrated a 7.5-kb signal in all
      tissues tested and in vitro translation analysis showed a 54-kDa polypeptide.
      These results indicate that both mouse and human RCK/P54 are highly conserved.

PMID- 8543179
TI  - Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death.
AB  - Typical programmed cell death requires de novo macromolecular synthesis and
      shares common morphological changes referred to as apoptosis. To elucidate the
      molecular mechanism of apoptosis, we isolated cDNA clones that are induced in
      various types of apoptosis by the differential display method. Among such clones,
      the MA-3 mRNA was induced in all apoptosis-inducible cell lines tested so far,
      including thymocytes, T cells, B cells and pheochromocytoma. The nucleotide
      sequence of the MA-3 cDNA predicted an amino acid (aa) sequence of 469 aa, which
      did not reveal significant similarity to any known proteins and functional aa
      motifs in databases. The MA-3 mRNA was strongly expressed in the thymus although
      small amounts of the MA-3 mRNA were ubiquitously expressed in mouse adult
      tissues. The MA-3 gene was highly conserved during evolution and cross
      hybridization bands were found not only in vertebrates but also in Drosophila
      melanogaster.

PMID- 8543180
TI  - Cloning of a cDNA encoding rat aldehyde dehydrogenase with high activity for
      retinal oxidation.
AB  - Retinoic acid (RA), an important regulator of cell differentiation, is
      biosynthesized from retinol via retinal by a two-step oxidation process. We
      previously reported the purification and partial amino acid (aa) sequence of a
      rat kidney aldehyde dehydrogenase (ALDH) isozyme that catalyzed the oxidation of
      9-cis and all-trans retinal to corresponding RA with high efficiency [Labrecque
      et al. Biochem. J. 305 (1995) 681-684]. A rat kidney cDNA library was screened
      using a 291-bp PCR product generated from total kidney RNA using a pair of
      oligodeoxyribonucleotide primers matched with the aa sequence. The full-length
      rat kidney ALDH cDNA contains a 2315-bp (501 aa) open reading frame (ORF). The aa
      sequence of rat kidney ALDH is 89, 96 and 87% identical to that of the rat
      cytosolic ALDH, the mouse cytosolic ALDH and human cytosolic ALDH, respectively.
      Northern blot and RT-PCR-mediated analysis demonstrated that rat kidney ALDH is
      strongly expressed in kidney, lung, testis, intestine, stomach and trachea, but
      weakly in the liver.

PMID- 8543181
TI  - Characterisation and chromosomal localisation of the rat alpha- and beta-adducin
      encoding genes.
AB  - A polymorphism in the genes encoding alpha- and beta-adducin (ADD) was described
      as being associated with blood-pressure variation in a genetically hypertensive
      strain of rats (MHS). ADD is a cytoskeletal heterodimeric protein which may be
      involved in cellular signal transduction and interacts with other membrane
      skeleton proteins which affect ion transport across the cell membrane. The cDNA
      encoding the alpha subunit of rat ADD was isolated using PCR methods. The cDNA
      consists of about 3900 bp and encodes a protein of 735 amino acids (aa) which
      shows 91% aa identity with the human counterpart. In spleen and kidney, three
      alternative spliced exons were found by PCR amplification and confirmed by RNase
      protection analysis. 17 inbred rat strains were genotyped for the polymorphism in
      the alpha- and beta-ADD genes. Chromosomal localisation mapped rat alpha-ADD on
      chromosome 14 and rat beta-ADD on chromosome 4.

PMID- 8543182
TI  - Cloning and analysis of the coding region of the histone H1(0)-encoding gene from
      rat PC12 cells.
AB  - We have determined the complete coding sequence of the histone-encoding H1(0)
      gene from rat PC12 cells. Southern and Northern analyses suggest that rat H1(0)
      is encoded by a single-copy gene which generates an mRNA of about 2.2 kb.
      Comparison of the rat, mouse and human amino-acid sequences shows that the C
      terminal domain of the protein is much more variable than the N-terminal and
      central domains. Rates of non-synonymous and synonymous nucleotide substitution
      have been calculated. The rate of non-synonymous substitution is about 2.5-times
      higher in the rodent lineage than in the human lineage.

PMID- 8543183
TI  - Cloning and sequence of a processed p53 pseudogene from rat: a potential source
      of false 'mutations' in PCR fragments of tumor DNA.
AB  - We describe here the nucleotide (nt) sequence of a p53 processed pseudogene (psi
      gene) from the normal F344 rat genome. Exon-derived primers were utilized to
      amplify and clone a 1447-bp polymerase chain reaction (PCR) product corresponding
      to the coding regions of exons 2-11 of the functional gene. This psi-gene is a
      cDNA-like sequence possessing 87% homology with the functional rat p53. We have
      also partially characterized two additional and distinctly different putative rat
      p53 psi-genes, focussing on the sequences surrounding the reported rat p53
      mutational hot spots of codons 202R and 211R within exon 6/7. Each of these three
      psi-gene sequences contained various single- and/or double-nt substitutions,
      small deletions and insertions that distinguish them from p53. One substitution,
      211R CGG-->CAG, found both in the cloned psi-gene and in one of the partially
      characterized, putative psi-genes, corresponded precisely with the sequence that
      has been reported as a mutation at one of the hot spots. Co-amplification of one
      or more of the p53 psi-genes with portions of the functional p53 is likely, if
      exon-based primers are utilized for PCR amplification of rat p53. Consequently,
      psi-gene sequences are potential sources of sequence variations that can be
      misidentified as somatic cell mutations by direct sequencing of inappropriately
      generated PCR products.

PMID- 8543184
TI  - Identification and characterisation of a novel human RNA-binding protein.
AB  - The processing of heterogeneous nuclear RNA (hnRNA) into a mature message occurs
      within a number of different nuclear ribonucleoprotein (RNP) complexes which bind
      to the hnRNA and provide the machinery for these modifying events. Although some
      components of the nuclear RNP complexes have been isolated, many remain to be
      elucidated. We report here the isolation of a novel human nucleic-acid-binding
      protein isolated by screening a lambda gt11 expression library with an
      oligodeoxyribonucleotide probe. The complete cDNA clone (E5.1) is homologous to a
      recently published murine sequence. The human gene encodes a ubiquitously
      expressed mRNA sequence with a putative open reading frame of 305 amino acids and
      contains a number of domains found in well characterised RNA-binding proteins.
      The E5.1-derived RNA recognition motif (RRM) is phylogenetically most related to
      the hnRNP C protein, a component of heterogeneous nuclear RNP particles which
      participates in mRNA splicing in vitro. E5.1 may, therefore, represent a novel
      gene, encoding a protein involved in processing of precursor RNAs into mature
      mRNA.

PMID- 8543185
TI  - Nucleotide sequences of novel potato (Solanum tuberosum L.) MADS-box cDNAs and
      their expression in vegetative organs.
AB  - Two similar, apparently full-length potato cDNAs, POTM1-1 and POTM1-2, from an
      early tuber cDNA library have been identified and sequenced. These two cDNAs
      encode 250 identical amino acids (aa) including 56 aa of the MADS-box domain and
      53 aa of the K-box domain, indicating that they may function as transcription
      factors. The transcripts of these cDNAs accumulate abundantly in vegetative
      organs, suggesting that these novel MADS genes may be involved in vegetative
      organ development of potato.

PMID- 8543186
TI  - Completion of a cDNA sequence from a tobamovirus pathogenic to crucifers.
AB  - Turnip vein-clearing virus (TVCV) is a tobamovirus related to ribgrass mosaic
      virus. We report the nucleotide (nt) sequences of the 5'-untranslated region
      (UTR) and the 3'-half of the TVCV genome (the 3' region of the 182-kDa protein
      encoding gene, as well as the movement protein and coat protein genes and the 3'
      UTR). The determination completes the nt sequence of the cDNA of TVCV.

PMID- 8543187
TI  - Cloning of the mouse gonadotropin beta-subunit-encoding genes, I. Structure of
      the follicle-stimulating hormone beta-subunit-encoding gene.
AB  - More than 16kb of genomic sequence encompassing the mouse follicle-stimulating
      hormone beta subunit (FSH beta)-encoding gene was isolated from a 129SvEv mouse
      genomic library. Comparisons of the nucleotide and deduced amino-acid sequences
      to the FSH beta sequences of other mammalian species confirm an evolutionarily
      conserved role of this important protein in reproduction.

PMID- 8543188
TI  - Cloning of the mouse gonadotropin beta-subunit-encoding genes, II. Structure of
      the luteinizing hormone beta-subunit-encoding genes.
AB  - A genomic clone encoding the mouse luteinizing hormone (LH) beta-subunit was
      isolated. The nucleotide and the deduced amino-acid sequences show high identity
      to the rat, bovine and human homologues. This confirms an important role of LH,
      together with follicle-stimulating hormone (FSH), in regulating several aspects
      of reproduction.

PMID- 8543189
TI  - Assignment of the E4TF1-60 gene to human chromosome 21q21.2-q21.3.
AB  - The gene encoding human transcription factor E4TF1-60 was previously mapped to
      chromosome 21q21. We analyzed the localization of the E4TF1-60 gene in more
      detail by genomic Southern hybridization and determined the sequence of the exons
      and the regions surrounding the intron boundaries. We report here that E4TF1-60
      locates in the long arm of chromosome 21 at q21.2-q21.3 and contains a total of
      ten exons.

PMID- 8543190
TI  - A novel NF-kappa B p65 spliced transcript lacking exons 6 and 7 in a non-small
      cell lung carcinoma cell line.
AB  - Transcripts of the gene encoding the p65 subunit of the NF-kappa B/Rel
      transcription factor complex have been reported to undergo alternative splicing
      to generate one derivative lacking codons for amino acids (aa) 222 to 231 (p65
      delta 1) and another that lacks codons for aa 13 to 25 (p65 delta 2) of the
      conserved Rel homology domain [Narayaran et al., Science 256 (1992) 317-320; Lyle
      et al., Gene 138 (1994) 265-266]. We have identified a third splicing event in a
      non-small-cell lung carcinoma cell line that potentially generates a novel p65
      mRNA derivative lacking codons for aa 187 to 293 (p65 delta 3) of the Rel
      homology domain.

PMID- 8543191
TI  - Characterization of the human XPA promoter.
AB  - We cloned the human xeroderma pigmentosum group A gene (XPA) and characterized
      the XPA promoter (pXPA) by transient cat expression. The pXPA is extraordinarily
      weak in human fibroblasts (1% of RSV-LTR) and appears to function without any of
      the usual promoter elements. Regions containing positive and negative control
      elements were localized.

PMID- 8543192
TI  - Cloning of the rat Gadd45 cDNA and its mRNA expression in the brain [Gene 151
      (1994) 253-255].

PMID- 8543193
TI  - Geriatrics' growing pains. Each of six decades has brought challenges; today's
      changes are setting a new course for medicine's future.

PMID- 8543194
TI  - 'Winter itch': what's causing this rash?

PMID- 8543195
TI  - FDR and hypertension: if we'd only known then what we know now.
AB  - Fifty years ago, when President Roosevelt died of complications from severe
      hypertension, there was no effective medication to reduce elevated blood
      pressure. Since then, three breakthroughs have contributed significantly to the
      successful management of hypertension: actuarial and observational studies that
      have identified risk factors for cardiovascular disease; the development of safe
      and effective antihypertensive drugs; and prospective, randomized trials that
      have shown the effectiveness of antihypertensive therapy. Mortality from stroke
      has decreased by almost 60% and mortality from heart attack by almost 50%. Even
      so, many hypertensives remain unidentified and untreated, a challenge for today's
      physicians.

PMID- 8543196
TI  - Ventricular tachycardia: progress in acute and chronic patient care.
AB  - Patients with ventricular tachycardia (VT) typically have significant structural
      heart disease and therefore benefit from all advances made in the past 50 years
      in cardiovascular care. Once sinus rhythm is restored, subsequent treatment goals
      include detecting the primary causes of VT and treating acute recurrences,
      determining the extent of structural heart disease and assessing the need for
      treatment of heart failure and ischemia, and prescribing chronic antiarrhythmic
      therapy. Implantable-device therapy has revolutionized the treatment of patients
      with VT.

PMID- 8543197
TI  - Renal failure: why today's patients live better and longer.
AB  - The clinical courses of two older patients with progressive renal failure
      associated with hypertension are described. Their underlying disorders are
      similar, but there are stark contrasts between medical therapies available now
      and 50 years ago. Such advances include the development of antihypertensive drugs
      and antimicrobial medications that have reduced the incidence of renal failure.
      In addition, recombinant erythropoietin and calcitriol have decreased the
      morbidity associated with chronic renal failure. Finally, technologic
      breakthroughs in dialysis have made a once-fatal condition eminently treatable.

PMID- 8543198
TI  - Progress in rheumatology: understanding autoimmune disease.
AB  - Fifty years ago, Wegener's granulomatosis was a uniformly fatal condition; the
      diagnosis was usually made post-mortem. Today, many patients survive, with a 93%
      complete remission rate reported 4 years after diagnosis. Four medical advances
      over the past 50 years have enhanced our understanding and management of this
      rheumatologic disorder. They are a rational classification of the vasculitides,
      development of a diagnostically useful serologic assay, successful treatment with
      cyclophosphamide, and novel ideas as to etiology.

PMID- 8543199
TI  - Endocrine disorders: new technology allows quick, accurate diagnosis.
AB  - In the past 50 years, the development of radio-immunoassay and other precise
      diagnostic tools has led to elucidation of the pathophysiology of many endocrine
      disorders. This in turn has enabled clinicians to make quick, accurate diagnoses
      of diseases that increase in frequency with advancing age, such as thyroid
      disorders, diabetes, osteoporosis, and hyperparathyroidism. Specific, effective
      therapies such as the oral sulfonylureas for diabetes and both hormonal and
      nonhormonal treatments for osteoporosis have improved the longevity and quality
      of life of older individuals with these diseases. Newer tests give us the ability
      to closely monitor therapeutic effectiveness.

PMID- 8543200
TI  - Parkinson's and Alzheimer's: new tools, new attitudes in patient care.
AB  - In 1946, the differential diagnosis of cognitive failure resided in the hands of
      psychiatrists. Not until the late 1960s was permanent doubt cast on the
      arteriosclerotic origins of dementia. Neuro-diagnostic studies 50 years ago were
      limited to skull x-rays. Many neurologic signs that would now be considered
      indicative of Parkinson's disease (PD) were thought in 1946 to typify old age.
      The diagnosis of PD was made on clinical grounds, and in that regard little has
      changed. For treatment of PD, textbooks then had little to offer, compared with
      the wide range of drug therapies available today. Unknown in the mid-1940s, the
      molecular biology of DNA now allows practitioners a glimpse at the highly complex
      and multifactorial origins of Alzheimer's disease.

PMID- 8543201
TI  - Healthy aging: guidelines for cancer screening and immunizations.
AB  - With increasing life expectancy over the past 50 years, screening for treatable
      illness and active measures to prevent disease and promote a healthy lifestyle
      have become increasingly important for older patients. In general, the benefits
      of such efforts have become more apparent, but depend also upon general health
      and life expectancy of the individual. Tests for malignancies of the breast,
      cervix, prostate, colon, skin, and oral cavity are considered to meet screening
      criteria. Immunization guidelines have been recently updated, and good evidence
      supports the benefit of protecting older patients from influenza and pneumococcal
      pneumonia. Counseling on prevention of falls and injuries in the home and on the
      highways can help reduce the risk of accidents.

PMID- 8543202
TI  - Healthy people 2000. At mid-decade, we examine initiative's implications for the
      care of older adults.

PMID- 8543203
TI  - Albrecht von Graefe. Facets of his work. On the occasion of the 125th anniversary
      of his death (20 July 1870)

PMID- 8543204
TI  - Autologous platelet concentrate for the treatment of full-thickness macular
      holes.
AB  - BACKGROUND: To improve the anatomic success rate in the surgery of full-thickness
      macular holes, we tested, in a prospective pilot study, the effects of autologous
      platelet concentrate deposited on the macula at the end of surgery. METHODS: Two
      consecutive groups of patients were compared. Twenty eyes (group 1, mean symptom
      duration 11 months) were operated on with injection of an autologous platelet
      concentrate on the macula after fluid-gas exchange. Another 20 eyes (group 2,
      mean symptom duration 11 months) were subsequently operated on without autologous
      platelet concentrate. For all stage 3 holes, posterior hyaloid was detached en
      bloc at the level of the optic disc. The patient was left supine for 24 h after
      surgery, and then remained face down for 10 days. RESULTS: In group 1, 19 cases
      were an anatomic success, i.e. there was flattening of the retina surrounding the
      hole and reattachment of the edge of the hole to the retinal pigment epithelium;
      in 9 cases the hole was even undetectable. Final visual acuity was 0.5 or more in
      9 eyes, and 0.4 or more in 14. Visual acuity improved by two lines or more in 17
      of the 19 successfully operated eyes. In group 2, only 13 cases were an anatomic
      success. The functional results for the successfully operated eyes were identical
      to those of group 1. CONCLUSION: These results strongly suggested that autologous
      platelet concentrate could significantly improve the success rate in macular hole
      surgery and led us to begin a comparative, prospective, randomized trial.

PMID- 8543205
TI  - Prevalence of dry eye in Japanese eye centers.
AB  - BACKGROUND: The purpose of the investigation was to ascertain the prevalence of
      dry eye in new outpatients. METHODS: A total of 2127 consecutive new outpatients
      seen in eight Japanese centers from April 1992 to January 1993 underwent
      comprehensive examinations, including double vital staining and measurement of
      tear film break-up time, basal tear secretion, and tear clearance. Dry eye was
      diagnosed if patients had abnormalities of both the tear film and the ocular
      surface. RESULTS: Three hundred fifty-nine patients (17%) had dry eye. There was
      no seasonal pattern for dry eye. The condition was significantly more common in
      Tokyo than in suburban areas (P < 0.01). The prevalence of dry eye in visual
      display terminal (VDT) users and contact lens (CL) wearers was significantly
      higher than in non-VDT users and non-CL wearers (P < 0.05 and P < 0.02,
      respectively). CONCLUSION: Our findings suggest that dry eye is one of the most
      common ocular disorders encountered by physicians. Furthermore, if patients use
      VDTs or wear CLs, the likelihood of dry eye occurring is higher.

PMID- 8543206
TI  - The effect of argon laser trabeculoplasty on the blood-aqueous barrier and
      intraocular pressure in human glaucomatous eyes treated with diclofenac 0.1%.
AB  - BACKGROUND: We studied the effect of argon laser trabeculoplasty (ALT) on the
      blood-aqueous barrier (BAB) in 41 eyes of 41 patients with primary open-angle
      glaucoma, pseudoexfoliation glaucoma, or pigment dispersion glaucoma using the
      Fluorotron Master II. METHODS: Fluorophotometry was performed the day before ALT
      and on the 3rd day after surgery at 30 and 60 min after intravenous injection of
      7 mg/kg body weight sodium fluorescein 10%. Intraocular pressure (IOP) was
      measured using Goldmann applanation tonometry on the day before surgery and at
      3rd days and 1 year (mean) after ALT. Patients were treated with argon laser by
      one surgeon (180 degrees, 0.1 s, 50 microns 0.6-1.0 W, 56 laser burns). Eyes were
      randomly assigned to either diclofenac-sodium 0.1% eye drops or vehicle. Eye
      drops were applied six times 1 h before ALT into the operated eyes and five times
      daily for 3 days postoperatively. RESULTS: On the 3rd day after ALT there was
      significant disruption of the BAB in the placebo-treated eyes compared to the
      diclofenac 0.1%-treated eyes. In the placebo-treated eyes as well as in
      diclofenac-sodium 0.1%-treated eyes there was a significant decrease of IOP
      postoperatively for up to 1 year. There was no significant difference concerning
      the IOP reduction after 1 year. Diclofenac-sodium 0.1% eye drops significantly
      stabilized the BAB on the 3rd day after ALT, compared to placebo, in this model.
      CONCLUSION: Diclofenac-sodium 0.1% significantly stabilized the disruption of the
      blood-aqueous barrier on the 3rd day after ALT. Concerning the IOP-lowering
      effect of ALT, the postoperative application of steroids should be avoided.

PMID- 8543207
TI  - Long-term results of non-filtering surgery for the treatment of primary angle
      closure glaucoma.
AB  - BACKGROUND: We previously reported the effectiveness of goniosynechialysis and
      trabeculotomy ab externo for adult-onset glaucoma. In this study, we performed
      non-filtering surgery on patients with primary angle-closure glaucoma and studied
      the long-term outcome of this treatment. METHODS: Included in this study were 35
      eyes of 25 patients with primary angle-closure glaucoma, each of which had an
      intraocular pressure greater than 20 mmHg with maximal tolerated antiglaucoma
      medication, even after laser iridotomy or surgical iridectomy. Of these 35 eyes,
      22 underwent trabeculotomy and 13 underwent goniosynechialysis. All patients were
      followed up for at least 18 months. RESULTS: In 21 (95%) of 22 eyes after
      trabeculotomy, and in 12 (92%) of 13 eyes after goniosynechialysis, intraocular
      pressures were well controlled at or below 21 mmHg at the final examination.
      However, in two of the 21 eyes in which trabeculotomy was a success, and in four
      of the 12 eyes in which goniosynechialysis was successful, the procedure had to
      be repeated before adequate control of pressure was achieved. CONCLUSION: Our
      results show that intraocular pressure in most cases of primary angle-closure
      glaucoma can be controlled by restructuring of the physiologic aqueous outflow
      route by means of goniosynechialysis or trabeculotomy, and that filtering surgery
      is not necessary.

PMID- 8543208
TI  - Effect of the cardiac cycle on topographic measurements using confocal scanning
      laser tomography.
AB  - BACKGROUND: This study was carried out to investigate the effect of the cardiac
      cycle on topographic measurements of the optic nerve head and peripapillary
      retina with confocal scanning laser tomography. METHODS: The sample comprised 25
      healthy subjects (mean age 40.44 years, range 23-67 years). Using a random
      crossover design, we obtained a set of three images using the Heidelberg Retina
      Tomograph (Heidelberg Engineering GmbH, Heidelberg, Germany) under each of two
      conditions. In the first, the images were obtained normally, while in the second,
      image acquisition was pulse-synchronised using an electrocardiographic signal. We
      compared the variability of topographic measurements under the two conditions in
      the whole image, in the optic nerve head and in the peripapillary retina free of
      visible vessels. RESULTS: Nineteen subjects (76%) showed a decrease in
      variability in the whole image under the pulse-synchronised condition. The
      respective numbers for the optic nerve head and peripapillary retina were 20
      (80%) and 21 (84%). The decrease in variability ranged widely, with a mean of
      13.62% in the whole image, 12.26% in the optic nerve head and 18.51% in the
      peripapillary retina. These decreases were highly significant. There was no
      relationship between the decrease in variability and age, intraocular pressure,
      blood pressure, heart rate or the area of the image occupied by blood vessels.
      CONCLUSION: Detecting structural change depends on the accurate assessment of
      each subject's variability. Because the cardiac cycle confounds this assessment
      by varying and unpredictable amounts, it may be necessary to obtain pulse
      synchronised images routinely.

PMID- 8543209
TI  - Time course of growth factor staining in a rabbit model of traumatic tractional
      retinal detachment.
AB  - BACKGROUND: This study examined the relationship between growth factor expression
      and cellular proliferation during the evolution of traumatic tractional retinal
      detachment (TRD) in a rabbit model. METHODS: TRD was induced in 15 pigmented
      rabbits by treating the inferior retina with cryopexy and making a scleral
      incision superiorly. Sections from varied time points were stained in the same
      assay with mouse monoclonal antibodies (MAb) specific for basic fibroblastic
      growth factor (bFGF) and platelet-derived growth factor (PDGF-BB/AB). RESULTS:
      Initially, the eyes exhibited intense vitritis; discrete membranes were present
      at 7 days and progressed to tractional retinal detachment at 17 and 28 days,
      after which there was no clinical change. At 6 and 24 h, bFGF, PDGF, and
      proliferating cell nuclear antigen (PCNA) were not detectable in membranes or
      wound sites (except for PDGF-positive inflammatory cells). On days 7, 17, 28, and
      52, bFGF and PDGF were readily detectable in most membranes. Cellular
      proliferation as detected by PCNA staining was also present on days 7, 17, and
      28, but was absent by day 52 despite growth factor staining. At all times, PCNA
      staining, which was most intense at the wound site, showed only limited
      correlation with staining for either growth factor for individual cells. Muller
      cells stained positively for PDGF-BB/AB in 13 of the 15 TRD eyes, but in none of
      the normal eyes. CONCLUSIONS: Since cellular proliferation correlated
      incompletely with the staining for bFGF and PDGF, these growth factors may not
      account exclusively for cellular proliferation within the membrane. Their
      distribution, however, including PDGF staining of Muller cells and bFGF staining
      at the vitreous-membrane interface, suggests that they may have roles in the
      pathogenesis of TRD.

PMID- 8543211
TI  - Experimental use of space-retaining substances with extended duration: functional
      and morphological results.
AB  - BACKGROUND: In glaucoma surgery, e.g. cyclodialysis ab interno, to date no
      viscous substances have been available that stay in the cyclodialysis cleft long
      enough to prevent scarring. We examined the qualities of two different
      viscoelastic substances that stay longer in the place of instillation than
      hyaluronic acid. METHODS: We performed cyclodialysis ab interno in 12 eyes of six
      owl monkeys. The right eyes were treated with the gel with the higher molecular
      weight, the left eyes using the gel with the lower molecular weight. The baseline
      data of intraocular pressure and outflow facility were compared to the values
      measured postoperatively up to the 140th day. Histological examination of the
      eyes followed. RESULTS: There was no statistically significant difference between
      the two substances. The mean intraocular pressure decrease was 7.9 (+/- 2.9) mmHg
      in the right eyes and 4.8 (+/- 2.7) mmHg in the left eyes. The histological
      examination showed that the gel had remained in the cyclodialysis cleft without
      signs of inflammation. In contrast to other viscoelastic substances studied
      previously, the substances in this study performed their space-retaining function
      without decreasing outflow facility. CONCLUSION: Both substances are suitable
      means of improving the rate of success of cyclodialysis ab interno, as they
      remain where they are instilled long enough to prevent wound scarring in the
      cyclodialysis cleft.

PMID- 8543210
TI  - Corneal endothelial permeability and aqueous humor flow using a standard
      protocol.
AB  - BACKGROUND: The study was carried out to compare corneal endothelial permeability
      and aqueous flow values of healthy volunteers measured in different countries
      with identical fluorophotometers using a standardized protocol. METHOD: Healthy
      volunteers aged between 20 and 70 years were studied in five European cities.
      Fluorescence scans of the anterior segment of both eyes were made using a
      commercial fluorophotometer. Beginning 4 h after instillation of four drops of
      fluorescein 10%, 12 scans of the anterior segment of each eye were performed in 2
      h. The values of corneal endothelial permeability and aqueous flow were
      calculated with standardized software from the decay of the fluorescein
      concentration in the cornea and anterior chamber. RESULTS: The mean permeability
      values (x 10(-4) cm.min-1) +/- SD were 3.7 +/- 1.6 (n = 19; Coimbra, Portugal),
      4.3 +/- 1.1 (n = 19; Frankfurt, Germany), 3.9 +/- 0.9 (n = 19; Leiden, The
      Netherlands) and 5.4 +/- 1.2 (n = 10; Milan, Italy). The values were not
      significantly different (ANOVA, P > 0.3), except those in Milan. The mean flow
      values (microliters.min-1) +/- SD were 2.3 +/- 0.9 (n = 17; Coimbra), 1.9 +/- 0.7
      (n = 10; Cologne, Germany), 2.6 +/- 1.2 (n = 19; Frankfurt), 2.0 +/- 0.6 (n = 19;
      Leiden) and 1.7 +/- 0.8 (n = 10; Milan). The values were not significantly
      different (Kruskal-Wallis test, P > 0.1). CONCLUSIONS: Permeability and flow
      values in the different cities had similar values and standard deviations. The
      Concerted Action demonstrated the usefulness of a standardized protocol.

PMID- 8543212
TI  - The effect of normal childbirth on eyes with abnormalities predisposing to
      rhegmatogenous retinal detachment.
AB  - BACKGROUND: Pregnant women who have high myopia, a history of retinal detachment
      or retinal holes, or have known lattice degeneration are frequently referred to
      an ophthalmologist for advice concerning the management of pregnancy and labor,
      i.e. whether a spontaneous vaginal delivery can be allowed and whether
      prophylaxis for high-risk retinal pathology is indicated. Many obstetricians
      still believe that pregnant women with ocular abnormalities predisposing to
      rhegmatogenous retinal detachment should have an instrumental delivery, and a few
      even advocate cesarian section. Very little has been written about the management
      of pregnant women with high-risk retinal pathology, and opinions differ
      considerably. Patient data on this subject are scarce. METHODS: We studied 10
      women who had 19 deliveries (10 prospective and 9 retrospective) and who had a
      history of retinal detachment, had been diagnosed as having extensive lattice
      degeneration, or had been treated for symptomatic retinal holes or breaks. The
      women were followed from the third trimester of pregnancy through labor and
      delivery into the postpartum period, looking for changes in the retinal status.
      RESULTS: We found no changes in the retinal status in the postpartum examination.
      CONCLUSION: We conclude that prenatal treatment of asymptomatic retinal pathology
      is not indicated and that spontaneous vaginal delivery may be allowed to take
      place in women with high-risk retinal pathology.

PMID- 8543213
TI  - Impact of dementia special care units: resource use and outcomes.

PMID- 8543214
TI  - Mortality crossovers and selective survival in human and nonhuman populations.
      New developments in mortality.

PMID- 8543215
TI  - Sex mortality differentials and selective survival in large medfly cohorts:
      implications for human sex mortality differentials.
AB  - Experimental studies on male-female mortality differences in nonhuman species are
      important because they provide insights into both the nature of age-specific
      gender differences and the concept of selective survival--whether one subgroup in
      a population (e.g., males) is consistently more frail than another subgroup
      (e.g., females). We found that it was not possible to classify either sex as more
      robust or longer lived since relative longevity was conditional on age (young or
      old), cage conditions (solitary confinement or grouped cages), and treatment
      (starvation, irradiation, or density). Implications of these findings are
      discussed including selective survival, demographic selection, a framework for
      male-female mortality differentials, and an evolutionary perspective on gender
      differences in longevity.

PMID- 8543216
TI  - Sex differences in human mortality and aging at late ages: the effect of
      mortality selection and state dynamics.
AB  - Models of gender differences in human mortality and aging depend on assumptions
      about temporal rates of physiological change. Simple models like the Gompertz
      fail to describe the mortality of either males or females at late ages. This
      suggests a need for biologically more detailed models to represent the age
      dependency of human mortality as well as gender differences in that age
      dependence. By modeling the sex-specific interaction of time-varying covariates
      with multiple dimensions of mortality selection, one can more accurately describe
      the age dependence of mortality and more complex physiological aging patterns.
      The multivariate model of aging changes is used to describe gender differences
      using data from (a) a longitudinal study of physiological changes and mortality
      and (b) a nationally representative longitudinal survey of changes in function
      and mortality.

PMID- 8543217
TI  - A biologically based explanation for mortality crossover in human populations.
AB  - We consider the impact of a genetically predetermined maximum life span (or upper
      bound on life span of a species) on patterns of human mortality. In particular,
      we consider the implication of a predetermined maximum life span on two distinct
      population subgroups: one group advantaged, the other group disadvantaged. We
      show that the existence of a genetically predetermined maximum life span imposes
      the condition that the two subgroup mortality rates must cross. We further
      observe that proportional mortality must be associated with divergent mortality
      differences over the life course. We illustrate these arguments via some
      simulated examples.

PMID- 8543218
TI  - The aging semantic differential: a confirmatory factor analysis.
AB  - The Aging Semantic Differential (ASD), which is used to measure attitudes and
      quantify bias and negative stereotypes toward older people, is a 32-item scale
      published more than 20 years ago (Rosencranz & McNevin, 1969). Several factor
      analytic studies failed to replicate the original three-factor structure.
      Confirmatory factor analyses (CFA) using 100 third-year medical students compared
      six-factor models derived from the gerontological literature. A modified version
      of Holtzman, Beck, and Kerber's (1979) four-factor model proved to be the "best"
      comparative fit based upon a consensus of fit indices.

PMID- 8543219
TI  - Competence of long-term care residents to participate in decisions about their
      medical care: a brief, objective assessment.
AB  - Data from 50 residents of a long-term care facility were used to examine the
      extent to which performance on a brief, objective inventory could predict a
      clinical psychologist's evaluation of competence to participate in decisions
      about medical care. Results indicate that the competence to participate in
      medical decisions of two-thirds of the residents could be accurately assessed
      using scores on a mental status instrument and two vignette-based measures of
      medical decision-making. These procedures could enable nursing home staff to
      objectively assess the competence of residents to participate in important
      decisions about their medical care.

PMID- 8543220
TI  - Elders' acceptability ratings of behavioral treatments and pharmacotherapy for
      the management of geriatric behavioral disturbances.
AB  - The management of geriatric behavioral disturbances presents a challenge for both
      caregivers and care receivers. Previously, we have investigated caregivers' and
      health care professionals' perceptions of the acceptability of behavioral
      treatments and pharmacotherapy. However, the perceptions of the potential or
      actual recipients of these interventions are equally important. In this study,
      vignette methodology assessed elderly individuals' acceptance of two behavioral
      treatments and one pharmacologic intervention using Kazdin's Treatment Evaluation
      Inventory. Respondents assigned the highest treatment acceptability ratings to
      behavioral treatments and the lowest to drug therapy. The place of patient
      residence described in the vignettes (community or nursing home) mediated
      treatment acceptability ratings.

PMID- 8543221
TI  - The long-term effects of later life spousal and parental bereavement on personal
      functioning.
AB  - Using data from Americans' Changing Lives: Wave 1, 1986, this study examined the
      long-term effects on the personal functioning of older women and men following
      the death of an adult child or a spouse. Guided by Weiss's (1993) theoretical
      framework, 41 bereaved parents and 143 bereaved spouses were compared to 407
      nonbereaved adults on measures of perceived health, self-efficacy, depression,
      life satisfaction, and future orientation. Analyses revealed bereavement and
      gender effects and a consistent influence of the sociodemographic characteristics
      of education, income, and duration of bereavement on functioning.

PMID- 8543222
TI  - Effect on physical functioning of care in adult foster homes and nursing homes.
AB  - This study tested the effects on physical functioning of substituting adult
      foster care (AFC) for nursing home care. Secondary data from Oregon's Medicaid
      agency were used to compare change in ADL functioning of 1,032 nursing home and
      279 AFC residents. Maximum likelihood estimation was used to analyze selection of
      long-term care setting and change in functioning. One-third of surviving AFC
      residents would have been better off in a nursing home, whereas almost all
      nursing home residents were placed appropriately. Further research on outcomes
      that clients value most along with efforts to support functioning are needed.

PMID- 8543223
TI  - The use of a computer-based model to implement an incontinence management
      program.
AB  - A computerized total quality management model was used to implement an
      incontinence system in eight nursing homes. Research staff measured resident
      wetness for one month, provided training in the implementation of the program in
      less than five days, and measured resident wetness for six months after
      implementation. Seven of the eight nursing homes significantly improved resident
      dryness for a six-month period. However, extensive monitoring of the nursing home
      computers by modem and telephone feedback from the research staff was necessary
      to produce successful maintenance.

PMID- 8543224
TI  - When seniors are abused: an intervention model.
AB  - An intervention model to combat abuse/neglect of seniors is outlined in this
      article. Central model elements are: (a) a "tool package"; (b) teams to design
      and execute intervention strategies, and advise on health, financial, and
      criminal/legal problems; (c) "volunteer buddies" to listen, monitor for abuse,
      and assist; (d) a victims' empowerment group; and (e) a community abuse committee
      for community advocacy/education. Three innovative elements, the tool package,
      volunteer buddies, and the empowerment group, are described in greater detail.
      Strengths of the model include its low additional cost; multidisciplinary,
      collaborative approach; use of validated abuse screens; evaluation of
      intervention strategies; and diversity of intervention elements.

PMID- 8543225
TI  - Bathing persons with dementia.
AB  - In the care of persons with Alzheimer's disease and related disorders, bathing
      frequently poses a formidable challenge for caregivers. This article reports the
      results of a consensus conference on techniques to reduce disruptive behaviors
      during bathing, and to make the process less stressful for persons with dementia.

PMID- 8543226
TI  - An older-worker employment model: Japan's Silver Human Resource Centers.
AB  - Over the past 20 years, a unique model of publicly assisted industries has
      developed in Japan, which contracts for services provided by retirees. Jobs for
      retirees are part-time and temporary in nature and, for the most part, are
      designed to assist in expanding community-based services. The program, known as
      the Silver Human Resource Centers, has expanded nationwide and reflects a novel
      approach to the productive engagement of retirees in society that may be
      replicable in other industrialized nations.

PMID- 8543227
TI  - Video Respite: an innovative resource for family, professional caregivers, and
      persons with dementia.
AB  - The development of a new and promising resource for family, professional
      caregivers, and persons with dementia is detailed in this article. The concept,
      Video Respite, refers to the initial goal of creating videotapes specifically for
      persons with dementia to capture and maintain their attention, enabling
      caregivers to have respite time. Ten 20-53-minute videotapes are described along
      with their potential benefits and limitations. Early research findings reveal
      that most persons with Alzheimer's disease (AD) watch and participate with the
      tapes, caregivers use the time for respite, and staff of SCU's report the tapes
      to be calming for the residents.

PMID- 8543228
TI  - An interdisciplinary behavioral treatment program for depressed geriatric
      rehabilitation inpatients.
AB  - Depression is known to be associated with increased functional dependence both in
      the community and in a hospital setting. An innovative interdisciplinary
      behavioral treatment of depression protocol is described here. Occupational
      therapists were trained to deliver a protocol of behavioral treatment techniques
      during their individual occupational therapy treatment sessions. Methods of
      training the occupational therapists and a description of the treatment are
      provided in this article. These methods insure that behavioral treatment is
      delivered accurately and regularly. An outline of each session is provided, and
      two case examples are described. Early results indicate that this form of
      treatment can be reliably and accurately carried out.

PMID- 8543229
TI  - Supportive seminar groups: an intervention for early stage dementia patients.
AB  - A supportive seminar group was developed and conducted for individuals with early
      stage dementia and their caregivers. The eight sessions focused on pertinent
      topics, namely, coping with memory problems, daily living, self-esteem,
      relationships, health, legal, and financial concerns. Content analysis of the
      evaluative statements from nine men and six women patients revealed positive
      themes of feelings of purposefulness, gratification, belongingness, and survival,
      while other themes reflected the turmoil of the disease, namely, feelings of
      helplessness, devaluation, and unpredictability. These preliminary findings lend
      support to the feasibility of a group approach for early stage dementia patients.

PMID- 8543230
TI  - A cognitive-behavioral program to improve geriatric rehabilitation outcome.
AB  - A program of cognitive-behavioral interventions was applied on a hospital
      geriatric rehabilitation unit. Unique features were the tailoring of the program
      to the population and each participant, and the immediate application of the
      program with distressed patients in a proactive manner designed to maximize
      rehabilitation outcome. The program was successful in that initially distressed
      participants achieved rehabilitation goals to the same extent as the
      nondistressed comparison group, and participant scores on measures of distress
      and coping, except for anxiety, matched those of comparison patients at
      discharge.

PMID- 8543231
TI  - A well-deserved break: respite programs offered by California's statewide system
      of Caregiver Resource Centers.
AB  - This article describes the range of respite care options that are helping
      families of cognitively impaired adults under the auspices of California's
      statewide system of Caregiver Resource Centers. Types of respite provided include
      in-home care, adult day care and other group care programs, and overnight respite
      options outside the home, ranging from short-term care of the patient in a
      facility to weekend retreats designed for caregivers. The hallmarks of the
      program are flexibility, choice, and consumer control.

PMID- 8543232
TI  - [Dead Sea bath salts for osteoarthritis of the knee].
AB  - 26 patients with osteoarthritis of the knees were randomly divided into 2 groups
      of 13 each with patients of similar ages, sex distribution and duration and
      severity of disease. All were treated with daily baths at 34-35 degrees C for 20
      min. containing Dead Sea bath salts (Group I) or sodium chloride (Group II). The
      study was double-blind and of 2 weeks duration. Patients were evaluated by a
      rheumatologist before, at the end of treatment and 1 month later. Clinical
      parameters evaluated included index of severity of osteoarthritis, patient's
      assessment of disease severity, range of movement of knees, soft tissue swelling,
      effusion and crepitus. There was significant improvement in the index of severity
      of osteoarthritis at the end of the treatment in both groups (p < 0.01). 1 month
      later, in Group I the significance of the index was still p < 0.01, but p < 0.05
      in Group II. Patient's assessment of improvement was significant only in Group I
      at the end of the treatment period (p < 0.01). There was no statistical
      improvement in either group in the other parameters assessed.

PMID- 8543233
TI  - [External fixation of the lower limb in children].
AB  - 18 children (13 boys, 5 girls) with displaced fractures of the femur (13 cases)
      and tibia (5) after road accidents were treated with Wagner external fixation. 5
      fractures were open and 13 closed. 9 also had head injury and were unconscious.
      In 3 fractures the popliteal artery was torn, requiring arterial reconstruction.
      15 were examined an average of 2.3 years after injury and there was full range of
      motion in 13. In 2 after severe injury, range of motion was 80% of normal. There
      was refracture after removal of external fixation in 1. We conclude that external
      fixation is stable and has minimal complications. We recommend it for children
      with comminuted fractures, multiple trauma and those in intensive care.

PMID- 8543234
TI  - [Bronchocentric granulomatosis].
AB  - We describe a 42-year-old woman with 3 solitary lung lesions in whom the
      diagnosis of bronchocentric granulomatosis was made by open lung biopsy. She
      presented with pleuritic chest pain, dry cough and fever. X-ray revealed 2
      solitary nodules in the lower lobe of the right lung, and another in the lingula.
      The pathologic findings included necrotizing granulomatous inflammation, mainly
      in the bronchi and bronchioles. The lesions of the right lung were resected,
      resulting in complete recovery from symptoms, while the nodule in the lingula
      resolved spontaneously.

PMID- 8543236
TI  - [Colorectal cancer of nonpolyp origin].

PMID- 8543235
TI  - [Purtscher's retinopathy].
AB  - A 20-year-old soldier trapped under a minibus for 90 minutes sustained a crush
      injury to his chest and a maxillofacial fracture. 2 days later he complained of
      decreased visual acuity in both eyes. Funduscopy revealed Purtscher's
      retinopathy. The traumatologist should be aware of this type of indirect eye
      injury, and should request ophthalmological assessment and follow-up in such
      patients.

PMID- 8543237
TI  - [Trigeminal neuralgia: role of neurogenic ectopic activity in the trigeminal
      ganglion].

PMID- 8543238
TI  - [Indication for use and mechanisms of action of intravenous immune globulin in
      autoimmune diseases].

PMID- 8543239
TI  - [Diagnostic aspects of IgA-fibronectin in serum of patients with IgA
      nephropathy].

PMID- 8543240
TI  - [Cisplatin and carboplatin--update].

PMID- 8543241
TI  - [Masseter muscle spasm--approach to patient].

PMID- 8543242
TI  - [Hearing loss following bacterial meningitis].

PMID- 8543243
TI  - [Javelin elbow].

PMID- 8543244
TI  - [Effect of ethanol on head injury].

PMID- 8543245
TI  - [A 15-year old boy with headache, convulsions, and hydrocephalus of recent onset
      and coma].

PMID- 8543246
TI  - [Coronary artery bypass without extra corporeal circulation].
AB  - 240 patients underwent coronary artery bypass grafting (CABG) without
      extracorporeal circulation (ECC). Mean grafts per patient was 1.9 (range 1-5).
      The internal mammary artery (IMA) was used in 210 cases (87%), but in only 53
      (22%) were there grafts to the circumflex marginals. Unfavorable results included
      an operative mortality of 7 cases (2.9%), nonfatal perioperative myocardial
      infarction (MI) (2.5%), stroke (0.4%), and sternal infection (1.7%). There were 2
      deaths among 17 patients (12%) with calcified aorta, and 4 among 40 (10%) who
      underwent emergency operation. Multivariate analysis showed these 2 risk factors
      to be the only predictors of early mortality: emergency operation odds ratio 9.8,
      and calcified aorta odds ratio 8.0. Perioperative risk factors that were not
      major predictors of early mortality or unfavorable outcome included left
      ventricular dysfunction (EF < 35%: 52 patients, 22%), congestive heart failure
      (53, 22%), cardiogenic shock (8, 3%), acute MI (67, 28%), age > 70 years (64,
      27%), renal failure (22, 9%), and stroke or carotid disease (12, 5%). Followup
      ranged from 1-31 months (mean 12). There were 9 late deaths (4 cardiac), and 18
      cases (7.5%) of early return of angina. 1-year actuarial survival was 92%; 192
      patients (80%) had uneventful outcomes and are doing well. Calcified aorta,
      nonuse of the IMA, reoperation, and diabetes mellitus were independent predictors
      of unfavorable events. We conclude that CABG without ECC can be performed with
      relatively low operative mortality, but there seems to be increased risk of early
      return of angina. It should therefore be considered for those patients with
      appropriate coronary anatomy in whom ECC poses a very high risk. However, it is
      still a hazardous procedure when used as as an emergency operation, and for cases
      with calcified aorta.

PMID- 8543247
TI  - [A national qualifying internal medicine examination for Israeli medical
      students].
AB  - In 1991 the deans of the 4 medical schools in Israel decided to institute a
      national qualifying examination in internal medicine. This marked the beginning
      of the process of unifying the qualifying examinations in all major medical
      fields. We describe the development of the examination, experience with its
      administration to 720 students in 1992-1994, and the outcome of this initial
      effort. The examinations were prepared by a committee of senior faculty from the
      4 schools, representing all the relevant clinical areas. Professional
      consultation was provided by the Unit for Medical Education of Tel Aviv
      University. Each examination consisted of 180 multiple choice items, reflecting
      an agreed representation of the various medical specialties, and was designed to
      test both comprehension and problem-solving ability. A syllabus was published by
      the committee and distributed to students and faculty in preparation for the
      examination. In composing the examination, the committee took into consideration
      differences in general policy and varying emphases in the curricula of the 4
      schools. Analysis of the results of the 3 annual examinations showed both a high
      level of reliability and high quality of the majority of the individual test
      items. There was a trend with time to slightly lower average scores, and fewer
      passed the exam last year. There was improvement in the results after the first 2
      years in the area of problem-solving related to interpretation of imaging, blood
      smears and clinical photographs, but this trend did not continue into 1994. The
      introduction of a high level examination based on a common syllabus provided
      important feedback, improving both student motivation and clinical teaching. For
      all schools, the outcome of the examination served as an important external
      indicator of teaching standards. Following this positive experience, uniform
      examinations in surgical subjects and pediatrics were introduced for the first
      time in 1993. The committee recommends that Israeli medical schools gradually
      introduce a comprehensive qualifying examination based on a mutually agreed list
      of objectives and syllabus.

PMID- 8543248
TI  - [Assessment by the primary care physician of his influence on the patient's
      hospital choice and of his own ability to evaluate hospital quality].
AB  - We report a mail survey (1993) of 677 primary care physicians employed by
      Israel's 4 sick funds of their influence on the patient's choice of hospital. In
      the light of the far-reaching changes currently taking place in the health system
      in Israel, factors considered by physicians in recommending a hospital were
      studied. About 50% reported having a high degree of influence over patient choice
      of hospital for elective procedures. Most reported themselves able to evaluate
      the quality of hospital care, especially results of clinical treatment (89%).
      Multivariate analysis revealed the physicians who reported a high degree of
      influence on patient hospital choice were men under the age of 65, independently
      employed by a smaller sick fund or by several sick funds. They considered
      themselves capable of evaluating hospital quality and were in regular
      professional contact with at least 1 hospital. The main factors considered in
      recommending a hospital were quality of its physicians and medical care, the way
      in which the hospital staff related to patients, and the level of equipment and
      technology available. Little importance was given to sick fund hospitalization
      policy. The survey findings had implications for primary care physicians, and for
      policymakers of the sick funds and the government.

PMID- 8543249
TI  - [Angioplasty for vein grafts and native coronary arteries after previous coronary
      artery bypass grafting].
AB  - 219 patients after previous coronary artery bypass grafting (CABG) underwent
      coronary artery or vein graft angioplasty in 1984-1991. 452 stenotic lesions out
      of 498 were successfully dilated in 337 procedures (90.7%). For arterial lesions
      the initial success rate had been 89.2% (321/360) and for vein graft lesions
      94.9% (131/138). For repeated angioplasty the success rate was the same. Major
      complications included 3 deaths (0.9%). 15 myocardial infarctions (5.3%) and 1
      emergency CABG. Factors that had reduced the success rate were lesions at the
      proximal anastomosis, total occlusions, and complex (type C) lesions. Time since
      grafting did not affect success rate of the second procedure. Restenosis after
      successful angioplasty was 37.3% (34/91) for arterial lesions and 56.8% (25/44)
      for graft lesions, after a mean time of 11.2 +/- 2.7 months. Restenosis was more
      common in type C lesions and old vein grafts. There was considerable improvement
      in treadmill exercise time of patients after the angioplasty (5.92 vs 7.31
      minutes) and in double product. During a follow up of about 3 years, 7.6%
      (15/196) died of cardiac events, 5.2% (10/189) had myocardial infarctions, 10.5%
      (20/189) were reoperated and 31.0% (68/219) needed at least 1 repeat angioplasty.
      Long term followup was better after angioplasty of native arteries than of
      grafts. After angioplasty of vein grafts, there were more cardiac related deaths,
      more MIs and more reoperations than after angioplasty of native arteries: 11.5%
      vs 3.5%, 9.6% vs 2.8%, 21% vs 4.9%, respectively, than in the arterial group.
      Considering the high mortality and morbidity of reoperation, balloon angioplasty
      in selected patients may be the preferred strategy. Clinical and angiographic
      results are better after re-angioplasty of native arteries than vein grafts.

PMID- 8543250
TI  - [Severity of testicular varicocele and sperm cell ultramorphologic
      characteristics].
AB  - Ultramorphologic characteristics of sperm cells found in infertile men with
      varicoceles were compared with the severity of the varicocele. Classification of
      varicoceles into mild, moderate or marked was determined by spermatic vein
      diameter and degree of blood reflux. These were evaluated by high resolution
      duplex sonography. There were no statistical differences between the 3 grades of
      varicocele severity with regard to abnormalities in the subcellular organelles of
      the acrosome, karyoplasm, and skeleton of spermatozoal heads, or in the axoneme,
      outer dense fiber and skeleton of sperm cell tails. The only abnormal
      ultramorphologic features found to be significant among the 3 groups were
      differences in the frequencies of karyoplasm agenesis, and of partial agenesis,
      malformation and degeneration of the acrosome in sperm cell heads. However, these
      features could not be related to grade of severity and therefore, no
      ultramorphologic severity pattern could be detected. Thus, no varicocele
      beneficial score based on grade of severity and sperm cell ultramorphology can be
      suggested for clinical use.

PMID- 8543251
TI  - [Laparoscopic surgery in children and adolescents].
AB  - Laparoscopic surgery is a rapidly developing field in general surgery. The
      advantages of laparoscopic procedures are short postoperative courses, fewer
      wound-related complications, possible reduction in rate of late postoperative
      adhesions and better cosmetic results. Laparoscopic procedures are indicated in
      well-defined clinical settings, after enough experience has been acquired and
      technical problems solved. Children and adolescents may also benefit from
      laparoscopic procedures. The technique is suitable for cholecystectomies,
      appendectomies in selected cases, splenectomies, anti-reflux procedures, bowel
      resections, and diagnostic procedures, among others. In the past 3 years we have
      performed 65 laparoscopic procedures in patients younger than 17 years, including
      10 cholecystectomies, 31 appendectomies and 7 Nissen fundoplications.

PMID- 8543252
TI  - [Intraoperative hepatic ultrasound, and surgical decision making].
AB  - Surgical resection of liver metastases might improve patient survival. Their
      number, location and relation to the intrahepatic blood vessels are of great
      importance in deciding whether to operate, the kind of operation (such as
      lobectomy, segmentectomy, wedge resection) and the surgical approach.
      Preoperative imaging modalities, including US, CT, MRI, isotope-scanning and
      sometimes portal angiography, are not sensitive enough to diagnose many liver
      lesions. Also, in many cases they do not give an absolute answer regarding the
      exact segmental location of the lesion and its relations to the major blood
      vessels. Intraoperative ultrasound is sensitive enough to detect most liver
      lesions, to locate them by liver segment, and to define their relationship to the
      hepatic vasculature.

PMID- 8543253
TI  - [Cerebral infarction in Crohn's disease].
AB  - Thromboembolic complications in Crohn's disease are not rare. Most of them are
      disseminated vascular thrombosis or pulmonary emboli. Cerebral artery thrombosis
      is a rare complication of Crohn's disease. We describe a 27-year-old woman who
      had Crohn's disease for 8 years, with exacerbation 3 months before admission. She
      had bloody diarrhea, abdominal pain, weight loss, weakness, and anemia.
      Hemoglobin was 6.3 g/dl and she received 3 packed cell transfusions the day of
      admission. Her hemoglobin level rose to 13 g/dl. 2 days after admission she had
      generalized tonic-clonic convulsions, followed by hemiparesis. EEG and CT
      examinations showed right temporal lobe infarction. Many studies report a
      hypercoagulable state in Crohn's disease, which results in a thromboembolic
      tendency that is potentially fatal.

PMID- 8543254
TI  - [Restorative proctocolectomy for ulcerative colitis and familial polyposis].
AB  - From 1987-1994 we performed 35 proctocolectomies with ileal pouch anal
      anastomosis. The indication for operation was ulcerative colitis in 29 and
      familial polyposis in 6. The mean ages at operation were 35 and 25 years,
      respectively. The most common postoperative complication was small bowel
      obstruction in 25% of the patients, requiring re-operation in half of them. The
      incidence of this complication may be reduced by operating in only 1 stage when
      possible, without creating a protective ileostomy. The second serious
      complication was pouchitis, in 17%, which was controlled by antibiotics. There
      has been no mortality. All patients, except for 2 with an S-shaped pouch,
      evacuate spontaneously a mean of 5 bowel movements a day. Continence was mildly
      impaired (usually night-staining of a pad) in 30% of patients in whom the pouch
      anal anastomosis was performed after stripping the mucosa of the rectal remnant.
      In those in whom the pouch-anal anastomosis was performed by means of the double
      stapling technique, continence was almost completely preserved. We therefore
      recommend that proctocolectomy with ileal pouch-anal anastomosis be performed in
      1 stage when possible, using the double stapling technique. Staged operation
      should be reserved for severely ill patients, or when stripping of the rectal
      mucosa is performed for familial polyposis and ulcerative colitis with severe
      dysplasia.

PMID- 8543255
TI  - [Cardiac lipoma of the septum with systemic and pulmonary emboli].
AB  - Cardiac lipoma is an uncommon tumor and is rarely a source of either lung or
      systemic emboli. A 46-year-old woman hospitalized because of left hemiplegia is
      presented. CT scan revealed a right temporo-parietal infarction. Chest x-ray
      showed a left lower lobe infiltrate. Pulmonary perfusion-ventilation scan
      indicated "high probability" of pulmonary embolism. Because brain and lung emboli
      are often associated, an echocardiogram was made and a 2 x 2 cm mass in the
      apical septum was found, confirmed by transesophageal echocardiogram. At
      operation a septal lipoma was resected. When pulmonary emboli occurs in
      association with systemic emboli, lipoma of the septum, although very rare,
      should be considered.

PMID- 8543256
TI  - [Abdominal wall endometriosis imitating incisional hernia].
AB  - Pain and swelling in abdominal wall scars that become more severe on coughing and
      straining, are typical symptoms of postoperative ventral hernias. Other abdominal
      wall lesions, such as hematomas, granulomas and neoplasms, can evoke similar
      symptoms. Usually the diagnosis can be made by physical examination, but
      occasionally only at operation. Endometriosis in a postoperative scar is rare,
      and the symptoms are usually associated with the menstrual cycle. We describe a
      40-year-old woman who suffered from pain and swelling in a cesarean section scar
      of 8 years duration. The symptoms worsened on coughing and during exercise. At
      operation, a 3 x 5 cm nodule was excised from the depths of the scar;
      endometriosis was found on histopathological examination. Endometriosis should be
      included in the differential diagnosis of abdominal scar lesions following
      gynecological operations.

PMID- 8543257
TI  - [Primary gastric tuberculosis].
AB  - Intestinal tuberculosis (TB) comprises 5% of all cases of TB and may be a major
      problem in immigrant communities, although the incidence of pulmonary TB is
      declining. Gastric TB is rare, constituting 0.1-2% of all cases of TB. Gastric TB
      usually develops secondary to other tuberculous lesions, most commonly pulmonary.
      On endoscopy antral infiltrative lesions are found. Primary gastric TB is very
      rare, only 8 cases having been reported in the English literature. We report a
      case of primary gastric TB in a 55-year-old woman who presented with abdominal
      pain and gastric outlet obstruction. The diagnosis was confirmed by endoscopic
      biopsies which showed granulomas, but no acid-fast bacilli. The Mantoux test was
      positive, acid-fast bacilli were found in the gastric juice, and a positive
      culture for TB was obtained on gastric lavage. There was an excellent response to
      antituberculous chemotherapy. With the relative rate of extra-pulmonary TB
      increasing, primary gastric TB should be taken into account in the differential
      diagnosis of infiltrative lesions of the antrum.

PMID- 8543258
TI  - [International postgraduate training program in medicine: survey of 13 training
      courses, 1988-1994].
AB  - In 1988 an International Postgraduate Training Program in Medicine was
      established as a joint venture of the Tel Aviv University School of Continuing
      Medical Education and the Ministry for Foreign Affairs, Division of International
      Cooperation. During 1988-1994, 359 physicians participated. A survey of 271
      graduates was carried out within 1-5 years following the completion of training,
      and 57% responded to our questionnaire. The program fulfilled the academic
      expectations of 78% of the trainees, and the practical clinical expectations of
      80%. 95% graded the program as good-to-excellent from the sociocultural aspect.
      75% and 67.5% of the trainees graded the program as good-to-excellent with regard
      to improvement in their theoretical and practical skills, respectively.
      Regretfully, only 45% have continued their ties with the host departments and
      only 11% have carried out joint research projects. These results imply that
      further attention should be paid to the trainees' real-time input, in order to
      increase satisfaction. Personal tutors should be nominated in each department,
      and should be adequately compensated. More emphasis should be given to initiation
      of bilateral research projects and maintenance of professional ties between the
      trainees and their host departments.

PMID- 8543259
TI  - [School health services--new horizons].

PMID- 8543260
TI  - [Beta-blockers in congestive heart failure--a therapeutic paradox].

PMID- 8543261
TI  - [Relationship between sleeping position and sudden infant death syndrome].

PMID- 8543262
TI  - [Group A streptococcal infections--from follicular tonsillitis to the "flesh
      eating bacteria" syndrome].

PMID- 8543263
TI  - [Sleep disorders and their impact on society].

PMID- 8543264
TI  - [Decisions regarding the technique of ECT].

PMID- 8543265
TI  - [Preventive treatment alternatives for deep-vein thromboembolism after total
      joint replacement].

PMID- 8543266
TI  - [Meningococcal arthritis].

PMID- 8543267
TI  - [Utility of Ca 19-9 tumor marker in pancreatic carcinoma].

PMID- 8543268
TI  - [Zidovudine therapy alone is not enough].

PMID- 8543269
TI  - [AIDS vaccine: who should be selected for the test?].

PMID- 8543270
TI  - [MR angiography: a methods with a future].

PMID- 8543271
TI  - [Prevention of coronary atherosclerosis. Determination and evaluation of lipid
      metabolism values].

PMID- 8543272
TI  - [Dermatomycoses. 14: Isolation and differentiation of the pathogenic fungi of the
      skin--direct detection].

PMID- 8543273
TI  - [Effectiveness of flupirtine in chronic tension headache. Results of a double
      blind study versus placebo].

PMID- 8543274
TI  - [Treating the slender type 2 diabetic patient early with insulin].

PMID- 8543275
TI  - [Parasitologic significance of the alteration of the causative Anisakidae worm
      and of the Pseudoterranova decipiens female immature adult worm, casting off the
      cuticles, and excreted from human in Kanazawa City].
AB  - We have been studying Anisakidae larvae, their intermediate hosts and their final
      hosts in the northern Japan Sea area. These larvae cause anisakidosis. According
      to the investigation, the recent burst of pseudoterranovosis in this area can be
      attributed to the increased presence of sea lions, which proliferate in the
      Arctic region, then migrate to the northern Japan Sea and eat the intermediate
      host fish. In a stomach of a male sea lion that was captured in February 1995, we
      found more than 4,500 Pseudoterranova decipiens. Although there is no known
      circumstance in which a human would consume an adult worm of Anisakis nematode,
      an astonishing case of this was found in Kanazawa; a female young adult
      Pseudoterranova decipiens undergoing the final metamorphosis was emitted from a
      patient. This indicates that the Anisakis larva can mature into the adult worm in
      humans. It is postulated that the Pseudoterranova decipiens larva is in the
      process of adapting to use humans as the final host.

PMID- 8543276
TI  - [Expression and role of Thy-1 on endothelial cells at sites of inflammation--a
      novel function of Thy-1; vascular permeability regulation].
AB  - We investigated the role of surface adhesion molecules in regulating vascular
      permeability, in vitro and in vivo. Cultured rat endothelial cells (RECs) express
      Thy-1, intercellular adhesion molecule-1 (ICAM-1), and CD44. Permeability of
      albumin across the REC monolayer increased through the interaction of Thy-1 and
      anti-Thy-1 monoclonal antibodies (mAbs), but no increase was seen through ICAM-1
      and anti-ICAM-1, CD44 and anti-CD44, and RT1A and anti-RT1A mAbs. The potential
      of anti-Thy-1 mAb for permeability increase depended on antibody concentration,
      it peaked at 12h, and was neither mediated by injury nor by growth modulation to
      the REC monolayer. Effect of anti-Thy-1 mAb was inhibited significantly by the
      calmodulin antagonist W-7 or the protein kinase inhibitors H-7 and HA-1004, and
      was completely blocked by the combined addition of W-7 and H-7. It seems likely
      that both calmodulin and protein kinases are involved in related intracellular
      signal pathways. Thy-1 expression on RECs was up-regulated with IL-1 beta
      treatment and was down-regulated with mixed lymphocyte reaction (MLR) supernatant
      treatment. Although Thy-1 expression on rat vascular endothelium in vivo was not
      detected, the expression of Thy-1 was induced on dermal endothelial cells at the
      site of inflammation induced by Freund's complete adjuvant (FCA). Vascular
      permeability in the inflamed dermis significantly increased when anti-Thy-1 but
      not anti-ICAM-1, anti-CD44, or anti-RT1A mAbs were given intravenously. The
      collective evidence suggests that inducible Thy-1 on the endothelium is one
      important regulatory event in vascular permeability at sites of inflammation.

PMID- 8543277
TI  - [Healing process of high porous EPTFE graft wrapped in the omental pedicle flap-
      experimental study of portal vein replacement].
AB  - This study investigates the healing process of high porous EPTFE graft wrapped in
      the omental pedicle flap. One way to provide good pseudointima is to use grafts
      with more porosity which allows increased cell infiltration into the inner
      capsule, and it is facilitated more by using grafts wrapped in the omental
      pedicle flap. We implanted two kinds of grafts at the portal veins of mongrel
      dogs. They are 60 microns fibril length EPTFE grafts, one with its outer surface
      covered by fluoridized rubber. (F-EPTFE graft), and the other without the
      covering (EPTFE graft). Grafts were extirpated and examined the implanted grafts
      at 1, 2, and 4 weeks after the implantation. We were seen on both grafts the
      developments of organization at the inner capsules, mainly from the anastomotic
      lines toward the midportion of the grafts. In addition, some developments of
      organization from outer side to inner side of the capsules were also seen. Light
      microscopy demonstrated endothelial lining at parts of insides of both grafts
      after 4 weeks with Factor-VIII staining. EPTFE grafts showed more developments of
      organization than F-EPTFE grafts and the degree of organization correlated with
      the degree of cell infiltration into the graft wall. The thickest pseudointima
      was found with the F-EPTFE grafts examined two weeks after the implantation.
      These results suggest that the cell infiltration into the graft wall facilitates
      the organization of inner capsules. We also investigated the expression of TGF
      beta, which was potent cytokine that promote fibrosis by enhancing the synthesis
      of extracellular matrix components. The immunohistochemical staining of TGF-beta
      positively stained vessels, vascular endothelial cells, macrophages, and spindle
      cells. Northern blot analysis suggested that TGF-beta was induced in the course
      of graft healing, and it promoted the production of extracellular matrix
      components.

PMID- 8543278
TI  - [Roles of Mac-1, endogenous TNF-alpha, and IFN-gamma in pathogenesis of hepatic
      warm ischemia-reperfusion injury].
AB  - The roles of neutrophil Mac-1 (CD11b/18) adhesion molecule, TNF-alpha and IFN
      gamma in hepatic warm ischemia-reperfusion injury (IRI) were investigated with a
      newly established mouse model. Blood supply to the left lateral and the median
      lobe of the liver was interrupted with an atraumatic clip for 50 minutes. From 1
      hour to 24 hours after reperfusion, TNF-alpha in the ischemic liver tissue was
      detected. IFN-gamma was not detected in ischemic liver tissue and blood.
      Pretreatment with anti-mouse Mac-1 monoclonal antibody (mAb) diminished the
      plasma GPT level, area of necrosis, and number of myeloperoxidase positive cells
      in ischemic liver lobe at 24 hours after reperfusion. Pretreatment with anti
      mouse TNF-alpha or anti-mouse IFN-gamma mAb did not affected any parameters. From
      these results, Mac-1 was considered to play an important role in a hepatic warm
      IRI. However, TNF-alpha and IFN-gamma were not considered to play a pivotal role
      in the pathogenesis of the injury and in the regulation of the neutrophils
      adhesion via Mac-1.

PMID- 8543279
TI  - [Studies on tissue distribution and expression of Epstein-Barr virus using
      polymerase chain reaction].
AB  - Epstein-Barr virus (EBV), a widespread human herpesvirus, establishes a life-long
      carrier state after primary infection. It is known that EBV infects mainly B
      lymphocytes and oral epithelia in vivo. However, other potential sites of EBV
      latent and/or permissive infection in human body have not been fully clarified.
      To investigate this, systemic autopsied tissues from 18 EBV-seropositive
      individuals without apparent EBV-related diseases were examined for EBV genomic
      DNA and virus-specific mRNA, by using the polymerase chain reaction technique.
      EBV DNA was frequently detected in oral mucosa/tongue/salivary gland, esophagus,
      stomach, lymph node and spleen; less frequently in bronchi, lung, kidney, adrenal
      gland, bone marrow and small intestine. In contrast, liver, gall bladder,
      pancreas, colon, heart muscle and urinary bladder contained no detectable EBV
      DNA. Reverse transcription-PCR analysis revealed that the latent membrane protein
      (LMP) 2A gene was expressed in all lymph nodes of the three cases studied, with
      LMP2B and EBV-determined nuclear antigen (EBNA) 1 transcripts in the lymph node
      and the LMP2A transcript in the stomach of one case. EBNA2 and LMP1 mRNA were not
      detected in any of the tissue specimens. The immediate early Bam HI-Z open
      reading frame no. 1 (BZLF1) gene, a key gene for EBV replicative cycle, was also
      expressed in the lymph nodes, but not in the spleen nor the stomach. These
      results indicate that EBV preferentially resides in the upper gastrointestinal
      tract and lympho-hemopoietic tissues where the cells harbor functionally active
      viral genomes. Moreover, the selective expression of the viral latent infection
      genes may provide advantages for EBV persistence in the setting of a host immune
      response. In addition, the localized detection of BZLF1 mRNA suggests that lymph
      nodes are another possible site of EBV replication in the asymptomatic virus
      carrier state in vivo.

PMID- 8543280
TI  - [Analysis of the human acidic epididymal glycoprotein-like molecule: isolation of
      cDNA and tissue localization].
AB  - Acidic epididymal glycoprotein (AEG) is an androgen-dependent, epididymal
      secretory protein assumed to play a major role in sperm maturation. In the
      present study, we isolated cDNA clones encoding the human AEG-like molecule and
      determined their nucleotide sequences. The deduced human AEG-like molecule was
      made up of 230 amino acids, excluding a signal peptide, and contained one
      potential N-linked glycosylation site. All cysteinyl residues were conserved
      between the human AEG-like molecule and the AEG molecules of rats and mice. The
      human AEG-like molecule was equally similar to the AEG molecules of rats and mice
      and a related testis-specific protein known as TPX1 of human and mice
      (approximately 40% amino acid sequence similarity). Northern blot analysis showed
      that the human AEG-like gene is expressed specifically in the epididymis. To
      identify the product of the human AEG-like gene, polyclonal antibody was produced
      by immunizing rabbits with a recombinant human AEG-like protein expressed in E.
      coli. This antibody detected a major band of 30 kD and a minor band of 26 kD in
      the caput, corpus, and cauda regions of the epididymis, the ductus deferens, the
      sperm, and the seminal plasma. Immunohistochemical analysis showed that the human
      AEG-like molecule is located in the lumen and epithelium of distal ductus
      efferentes and epididymal ducts, and on the postacrosomal region of the sperm
      head.

PMID- 8543281
TI  - [The effect of recombinant human hepatocyte growth factor on the functions of rat
      hepatocytes in primary culture].
AB  - The effect of recombinant human Hepatocyte Growth Factor (rhHGF) on
      gluconeogenesis, urea synthesis, ATP level and total protein amount of rat
      hepatocytes in primary culture was investigated for 5 days in culture. According
      to the rhHGF concentration in media (1,5,10 ng/ml), three groups were designed.
      The group added Epidermal Growth Factor (EGF) was chosen as a control group.
      Gluconeogenesis was increased significantly on day 1 by addition of HGF, not by a
      concentration dependency fashion, but urea synthesis was not activated by HGF and
      declined on day 5. ATP levels were maintained and kept high during the culture in
      the EGF group. But ATP levels in the HGF groups were lower than those of the
      control and significantly declined on day 5. The same tendency was observed in
      the total amount of protein. In the EGF group, total amount of protein was
      maintained throughout the experimental period, but the HGF groups could not keep
      the amount of protein of day 1 till day 5. Phase contrast microscopic findings
      also showed detachment and deformity of cells on day 5 in the HGF groups. These
      results suggested that HGF activated gluconeogenesis of the rat hepatocytes in
      primary culture in early days, but it did not activate urea synthesis, and
      prolonged exposure of HGF caused to decline intracellular ATP levels and led to
      cell death in culture condition, which was speculated that the strong effect on
      hepatocytes by HGF exhausted cell energy. HGF was thought to be unfavorable in
      the respect of maintenance of primary cultured hepatocytes, but further studies
      are needed to confirm this speculation.

PMID- 8543282
TI  - [Analysis of the cellular tropism of human polyoma JC virus (JCV)].
AB  - Human polyomavirus JC virus (JCV) is the causative agent of the demyelinating
      disorder progressive multifocal leukoencephalopathy (PML). In vivo the cellular
      tropism of JCV has been shown to be very narrow, and replication appears to be
      essentially restricted to oligodendrocytes. To investigate the detail cellular
      tropism of JCV, we employed transfection, microinjection and CAT assays using JCV
      permissive cells, and several non-permissive cell lines. IMR-32 (human
      neuroblastoma cells) was permissive for IMR-32 adapted JC virus. A431 (human
      epidermoid carcinoma) and COS-7 (a SV40 transformed African green monkey kidney
      cell line) were used as non-permissive cells. Employing infection it could be
      confirmed that the virus proliferated in IMR-32, but not in A431 and COS-7 cells
      as measured by immunofluorescence methods. However, after microinjection of IMR
      32 adapted JCV it could be shown that virus could replicate not only in IMR-32
      but also in COS-7 cells. Virus could not be replicated in A431 cells. Using CAT
      assays the regulatory region of IMR-32 adapted JCV was shown to be active in IMR
      32 and COS-7 cells, but inactive in A431 cells. The result suggests that nuclear
      transcription factors are also determinant of JCV cell tropism in vivo in
      addition to specific cellular receptors.

PMID- 8543283
TI  - Marshall T. Newman (1911-1994).

PMID- 8543284
TI  - DYS19, D12S67, and D1S80 polymorphisms in population samples from southern Italy
      and Greece.
AB  - Genotype and allele frequencies of the DYS19, D12S67, and D1S80 highly
      polymorphic loci were determined in population samples from southern Italy (103
      subjects) and Greece (84 subjects) using the amplified fragment length
      polymorphism (AFLP) technique (polymerase chain reaction followed by native PAGE
      and silver staining). Five, eleven, and eighteen alleles were found at the DYS19,
      D12S67, and D1S80 loci, respectively. PIC values ranged from 0.55 (DYS19 locus in
      Italians) to 0.79 (D12S67 locus in Italians). The distribution of D12S67 and
      D1S80 genotypes conformed to Hardy-Weinberg equilibrium, as confirmed by three
      statistics. Heterogeneity G tests, carried out on allele frequency distributions,
      showed a significant difference between the samples at the DYS19 locus, whereas
      no difference was found with regard to the other polymorphisms. Using data from
      the literature, we widened the comparison to other European groups analyzed for
      the same markers. All the polymorphisms were found to distinguish between
      populations of the same main ethnic group. In particular, D1S80 allele
      frequencies distinguished the Finns from other European groups (Spanish, German,
      Italian, and Greek samples). The reduced assay time, the high polymorphism level,
      and the ability to distinguish between populations indicate that these markers
      have potential value in population genetic studies.

PMID- 8543285
TI  - Are the SSTR alleles stable enough to be considered monophyletic and hence
      reliable anthropogenetic markers? Linkage disequilibrium study on the (ACT)n
      COL1A2 SSTR.
AB  - An extremely low production rate of a polymorphic allele (formally called the
      mutation rate)--a prerequisite for using the allele as a marker (particularly for
      anthropogenetic purposes where the alleles must be assumed to be monophyletic)-
      cannot be taken for granted for alleles of highly polymorphic VNTRs, but a low
      production rate can be used to identify alleles produced by a single nucleotide
      substitution. This property was indirectly tested for the (ACT)n COL1A2 (of type
      I collagen) microsatellite SSTR (degree of heterozygosity H = 0.72) by searching
      for linkage disequilibria between the SSTR's four common alleles (n = 6, 8, 9, or
      10) and three RFLPs of the same gene. A strong linkage disequilibrium between at
      least three of the four SSTR alleles and two of the three closely linked RFLPs
      has been demonstrated in a Sardinian population (Italy), a finding that suggests
      a low production rate of these alleles. Thus it seems that this highly
      polymorphic system and, by a reasonable extrapolation, other VNTRs with a
      comparable degree of heterozygosity may be valuable anthropogenetic markers, at
      least in distinguishing subgroups of a major ethnic group.

PMID- 8543286
TI  - Butyrylcholinesterase polymorphisms (BCHE and CHE2 loci) in Brazilian Indian and
      admixed populations.
AB  - The genetic variability of butyrylcholinesterase, determined by the BCHE and CHE2
      loci, was examined in nine Brazilian Indian groups. In addition, a search for the
      presence of the BCHE*F allele was also performed in eight other Brazilian Indian
      samples and in five admixed (black-Indian-white) rural Amazonian communities
      previously studied for the CHE2 locus and the BCHE*A allele. In the Indian
      populations the frequency of the BCHE*F allele varied from 0 to 7.1% +/- 3.4 and
      the frequency of the CHE2 C5+ phenotype ranged from 1.4% +/- 1.4 to 45.9% +/-
      3.8. This study seems to be the first to report the presence of the BCHE*F allele
      in native Americans. The BCHE*A allele appeared in one Indian group (1.4% +/-
      1.0), and we suggest that its existence in this tribe and in other native
      Americans can be explained by gene flow from white populations. Gene flow may
      also be the reason for the occurrence of the BCHE*F allele in Brazilian Indians,
      whereas the CHE2*C5+ allele may have been present in the paleo-Indians. The
      distributions of both the BCHE*F allele and the CHE2 C5+ phenotype in Brazilian
      Indians seem to be the result of the action of random genetic drift.

PMID- 8543287
TI  - Genetic and environmental influences on somatotype components: family study in a
      Spanish population.
AB  - Parent-offspring, sibling, and spouse resemblances for Heath-Carter somatotype
      components were assessed in 261 nuclear families from the Madrid, Spain, area.
      Each phenotype was adjusted for the effect of (1) age and sex and (2) family
      environment variables and age and sex by means of multiple regression. Age and
      sex explained a significant (p < 0.001) proportion of observed variation, but in
      no case did the addition of family environment variables appreciably alter the
      amount of variance accounted for by age and sex. Familial correlations were
      estimated by maximum-likelihood procedures for each somatotype component after
      adjusting for age, sex, and the other two somatotype components. Furthermore,
      several hypotheses regarding sex-specific and generational differences among
      correlations were assessed for each phenotype. No spouse resemblance was found
      for somatotype components. Significant parent-offspring and sibling correlations
      point out consistent familial aggregation for somatotype components, especially
      for mesomorphy. Familial correlations for mesomorphy were significantly (p <
      0.05) influenced by the sex of parents (offspring were more similar to their
      mothers than to their fathers) and to a lesser extent (0.05 < p < 0.10) by the
      sex of the offspring. The sex of siblings did not significantly alter sib
      correlations for any of the somatotype components studied.

PMID- 8543288
TI  - Common genetic influences on BMI and age at menarche.
AB  - Genetic influences on variability of body weight and onset of menarche are well
      known. To investigate the genetic and environmental contributions to the
      association of body weight with onset of menarche, we studied Finnish twins from
      consecutive birth cohorts (the FinnTwin16 study) ascertained from the national
      population registry, which identifies nearly 100% of all living twins. Baseline
      questionnaires were mailed to the twins within 60 days of their sixteenth
      birthday and later to older sibs of the twins. Pairwise response rates
      (approximately 85% across gender and zygosity) and 30 months of data collection
      yielded results from 1283 twin pairs. The questionnaires included a survey of
      health habits and attitudes, a symptom checklist, MMPI personality scales, and a
      survey of relationships with parents, peers, and the co-twin. Age at menarche was
      reported by 468 monozygotic (MZ) girls, 378 girls from like-sex dizygotic (FDZ)
      pairs, 434 girls from opposite-sex (OSDZ) pairs, and 141 older female sibs of the
      twins. The one-month test-retest reliability of age at menarche in an independent
      sample (N = 136) of 16-year-olds from a national survey was 0.96. Girls from OSDZ
      pairs had a significantly higher mean age at menarche (13.33 yr) than FDZ girls
      (13.13 yr) (difference, 0.20 yr; 95% confidence interval, 0.05-0.35). The MZ
      correlation for age at menarche was 0.75, the DZ correlation was 0.31, and the
      sib-twin correlation was 0.32. A bivariate twin analysis of age at menarche and
      body mass index (wt/ht2) indicated that 37% of the variance in age at menarche
      can be attributed to additive genetic effects, 37% to dominance effects, and 26%
      to unique environmental effects. The correlation between additive genetic effects
      on age at menarche and body mass index was 0.57, indicating a substantial
      proportion of genetic effects in common.

PMID- 8543289
TI  - Secular growth trend in two generations of the Russian population.
AB  - A retrospective sample survey of birth certificates from a Moscow maternity
      hospital over a 40-year period has revealed secular growth changes (involving
      mothers' stature, age at menarche, and four anthropometric traits in newborns) in
      two consecutive generations. Cohorts of mothers born in the period 1930-1949
      showed high rates of acceleration. Age at menarche decreased in these cohorts at
      a rate of 12.5 months per 10 years, and a parallel gain in stature averaged 1.8
      cm per 10 years; both rates were significantly higher than those for Western
      Europe. In later birth cohorts the acceleration in the maternal generation
      apparently ended. Anthropometric traits at birth (weight, body length, head and
      chest circumferences) show different patterns of secular changes from 1950 to
      1990. According to multiple regression analysis, a temporal trend in the neonate
      body size might be mainly due to the parallel increase in mother's stature. The
      contribution of socioeconomic factors to the observed secular growth changes is
      discussed.

PMID- 8543290
TI  - Prevalence of genetic versus environmental factors in human female temporal
      organization: preliminary analysis.
AB  - Genetic diversity among ethnic groups is studied by comparing the genetic
      fingerprint of the examined groups. This index is constructed by aggregating the
      differential frequencies of various marker characteristics. Recent advances in
      the study of human biological rhythms may provide new indexes that will
      complement the genetic profile of a population. One of the rhythm parameters that
      is especially useful for this purpose is the acrophase (peak time location). The
      aim of the present study is to construct a rhythm profile based on acrophase
      distribution for various human groups and to estimate the contribution of genetic
      and environmental factors to that profile. The rhythm profiles were constructed
      by comparing the acrophases of 11 plasma hormones in women from three different
      ethnic-geographic populations (North Americans, Romanians, and Japanese) with
      reference to three age groups (adolescence-early postpuberty, young adulthood,
      and postmenopause). Genetic distances of these ethnic groups were determined by
      14 genetic markers. Cluster and principal coordinates analyses were used to
      define the variation of the two parameters (genetic distances and acrophase
      dispersion). The analyses show that North Americans and Romanians are closer to
      each other with regard to both parameters and far apart from the Japanese.
      However, there was a difference between the variation presented by the first
      eigenvalue of the genetic profiles (94.5%) and that of the first eigenvalue of
      the acrophase pattern (69.1%), which means reduction in the variability
      (increased similarity) among the three ethnic groups according to the acrophase
      profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8543291
TI  - Differential fertility of mothers of twins and mothers of singletons: study in
      Limon, Costa Rica.
AB  - The reproductive performance of mothers of twins is of interest from an
      evolutionary perspective. Because mothers of twins have the potential of leaving
      a greater number of offspring, they could be favored by natural selection. At the
      same time, twin pregnancies are known to be associated with higher pre- and
      postnatal mortality. Thus mothers of twins at least have potentially higher
      fertility, a potential that may be hampered by greater mortality of twins. Here,
      I examine the completed fertility of 149 females, 50 years of age and older, from
      Limon, Costa Rica. In particular, the number of surviving children of mothers of
      twins and mothers of singletons at the time of the interview is compared. In this
      sample mothers of twins have a higher fertility at the end of their reproductive
      career. Their selection coefficient indicates that natural selection favors them
      through differential fertility.

PMID- 8543292
TI  - Application of two STRs (VWA and TPO) to human population profiling: survey in
      Galicia.
AB  - We have studied two tetranucleotide short tandem repeats (STRs) (VWA and human
      TPO) in 260 individuals from Galicia by means of polymerase chain reaction
      amplification followed by electrophoresis separation and silver staining. The
      feasibility of the analytical technique and the level of polymorphism attained by
      both systems (PIC = 0.764 for VWA; PIC = 0.563 for TPO) allow us to consider the
      two STRs as suitable and informative markers in routine population profiling
      studies.

PMID- 8543293
TI  - Complete map of cystic fibrosis mutation DF508 frequencies in Western Europe and
      correlation between mutation frequencies and incidence of disease.
AB  - The frequencies of DF508, the main cystic fibrosis mutation, vary among different
      populations in Western Europe; they are higher in northwestern Europeans than in
      southeastern populations. Our new analysis is based on results from 66 different
      laboratories on 17,886 cystic fibrosis chromosomes (from 70 locations and 26
      countries). The correlation between DF508 frequency values and cystic fibrosis
      incidence is calculated in the corresponding groups.

PMID- 8543294
TI  - P.C. Mahalanobis and the symposium on frontiers of anthropology.

PMID- 8543295
TI  - Genetic epidemiology of blood pressure in two Indian populations: some lessons.
AB  - A genetic epidemiological study of blood pressure was conducted in two
      contrasting populations: the Marwaris of Calcutta and the Hindu middle-caste
      agriculturists of Digha. The Marwaris are heavier and significantly more obese
      than the agriculturists. The prevalence of hypertension among the Marwaris (17%)
      is more than tenfold higher than that among the agriculturists (1.4%). Genetic
      analysis of blood pressure data using a path model indicates that blood pressure
      levels (adjusted and standardized for age, gender, education level, and disease
      status) are primarily determined by environmental factors, as measured by their
      effects on anthropometric characters. The observed familial resemblance of blood
      pressure levels in the two populations is primarily due to cultural rather than
      genetic inheritance. Genetic and familial effects on covariation between
      anthropometric measures of obesity and blood pressure levels are perhaps so
      strong that there is no residual genetic heritability of adjusted blood pressure
      levels.

PMID- 8543296
TI  - Genetic affinities of Sri Lankan populations.
AB  - Mythological and historical sketches of the Sri Lankan population indicate that
      it is heterogeneous and composed of diverse ethnic groups. Ancient chronicles of
      Sri Lanka relate the origin of the Sinhalese to the legend of Prince Vijaya, who
      arrived on the northwest coast of the island in 543 B.C. from northeast or
      northwest India. Further, because Sri Lanka occupies an important position on
      seaways, it has received a constant influx of people from various parts of the
      world (especially from the Middle East and Europe), including India. Taking into
      consideration mythological, historical, and linguistic records of Sri Lanka, I
      attempt to study the degree of gene diversity and genetic admixture among the
      population groups of Sri Lanka along with the populations of southern,
      northeastern, and northwestern India, the Middle East, and Europe. The genetic
      distance analysis was conducted using 43 alleles controlled by 15 codominant loci
      in 8 populations and 40 alleles controlled by 13 codominant loci in 11
      populations. Both analyses give a similar picture, indicating that present-day
      Sinhalese and Tamils of Sri Lanka are closer to Indian Tamils and South Indian
      Muslims. They are farthest from Veddahs and quite distant from Gujaratis and
      Punjabis of northwest India and Bengalis of northeast India. Veddahs are distinct
      because they are confined to inhospitable dry zones and are hardly influenced by
      their neighbors. The study of genetic admixture revealed that the Sinhalese of
      Sri Lanka have a higher contribution from the Tamils of southern India (69.86% +/
      0.61) compared with the Bengalis of northeast India (25.41% +/- 0.51), whereas
      the Tamils of Sri Lanka have received a higher contribution from the Sinhalese of
      Sri Lanka (55.20% +/- 9.47) compared with the Tamils of India (16.63% +/- 8.73).
      Thus it is apparent that the contribution of Prince Vijaya and his companions,
      coming from northwest India, to the present-day Sinhalese must have been erased
      by the long-standing contribution (over 2000 years) of the population groups of
      India, especially those from Bengal and Tamil Nadu. Similarly, the Tamils of Sri
      Lanka are closer to the Sinhalese because they were always in close proximity to
      each other historically, linguistically, and culturally.

PMID- 8543297
TI  - Proximate determinants of fertility in eastern Uttar Pradesh.
AB  - Our main objective here is to examine and discuss the effects of some
      sociocultural and economic factors on the proximate determinants of fertility in
      rural areas of eastern Uttar Pradesh (population more than 40 million persons).
      The region is known for its present demographic trends because the crude birth,
      death, and infant mortality rates are among the highest for India. The
      determinants considered are age at marriage of female, postpartum amenorrhea
      (PPA), fecundability and sterility, and menopause. The sociocultural and economic
      factors studied are caste, education, breast-feeding status, and social status of
      the currently married females in the reproductive age group. The study population
      is predominantly Hindu, among whom caste is a strong indicator of socioeconomic
      conditions. The average age of the female at return marriage (RM) is below 18
      years in each religion or caste group but has been increasing over time. Median
      durations of breast feeding and PPA differ significantly among various
      socioeconomic and demographic subgroups. These are longest in scheduled castes
      and shortest in upper-caste Hindus. As the social status of the household
      increases, the median durations of breast feeding and PPA decrease. The estimates
      of fecundability consistently decrease with age, whereas those of sterility
      increase with age after 35 years. The smallest estimate of sterility is 4%,
      corresponding to the 25-30-year age group in each religion or caste group.
      Occurrence of menopause is rare before age 35, and it increases with the age of
      the female irrespective of religion or caste. However, the risk is minimum for
      females in upper castes and maximum for those in scheduled castes.

PMID- 8543298
TI  - Reciprocity in marital and social networks: illustration with Indian data.
AB  - Three measures of reciprocity, denoted s2, s3, and s4, that are applicable to
      both simple and weighted networks are considered here. By reciprocity I mean
      symmetry or mutuality of ties between different vertices of the network. These
      measures have simple formulas except in some extreme situations and can be used
      for most networks. Among the three measures, s2 is generally preferred, although
      the choice in any situation depends on the validity of the assumptions underlying
      its derivation and its discriminating power. I illustrate how reciprocity in the
      network of marital exchanges between different surnames and settlements can
      reveal something about the structure of a population. Reciprocity is higher if
      the endogamous group is close-knit, is well settled in a smaller geographic area,
      and has a low surname diversity index. Thus reciprocity is high in the Vadde,
      somewhat high in the Pattusali, and low in the Yanadi. Although s2, s3, and s4
      measure reciprocity in a network as a whole, the local reciprocity index can be
      used to see how reciprocally a particular vertex is tied to others and can help
      in the study of the direction of the exchanges. The low local reciprocity indexes
      of the neighborhood settlements of the Yanadi in some regions indicate that the
      settlements are involved in one-way marital exchanges with other settlements. The
      study of reciprocity can be relevant in other contexts also. High reciprocity in
      a well-settled population was also observed in the social networks of 21 villages
      with respect to the "help" relation. It was found that reciprocity is highly
      negatively correlated with the percentage of migrants in the village but does not
      show high positive or negative correlation with other demographic, socioeconomic,
      and location characteristics of the villages.

PMID- 8543299
TI  - Allele and haplotype frequency distribution of the EcoRI, RsaI, and MspI COL1A2
      RFLPs among various human populations.
AB  - The EcoRI, RsaI, and MspI RFLPs (restriction fragment length polymorphisms) of
      the COL1A2 gene, one of the two genes that encode for the polypeptides of type I
      collagen, have been studied in four West African and two Asian populations to
      evaluate their potential effectiveness as anthropological markers. All three
      RFLPs were in Hardy-Weinberg equilibrium. The comparisons between present data on
      two of the major human groups and those on Europeans and Amerindians show a
      considerable heterogeneity for each of the three RFLPs under study. EcoRI, in
      particular, appears to be highly effective in distinguishing Africans, Europeans,
      and Asians from each other. As expected, the analysis at the haplotype level
      considerably improves the discriminating efficiency of these three markers by
      creating a clear-cut distinction between Tharus and Indonesians, the two Asian
      populations of the present survey. In fact, even though these two populations
      exhibit the same frequencies for the RsaI and MspI alleles, the frequency of the
      MspI(-) allele among the RsaI(-) chromosomes is 0.5 +/- 0.14 in the Indonesian
      sample and 0 + 0.04 in the Tharu sample.

PMID- 8543300
TI  - Ethnic comparison of twinning rates in California.
AB  - A meaningful comparison of the twinning rates of different populations can be
      hindered by several factors that may influence the rates. Chief among these
      factors are the sources of data from which the rates are derived and the maternal
      age structure of the populations. The effects of such factors were minimal when
      the twinning rates of 14 ethnic groups in California were compared. After
      standardization for maternal age, twinning rates per 1000 maternities for the
      main ethnic groups were 13.20 for blacks, 10.05 for whites, and 7.18 for Asians.
      There were significant differences within the Asian group. The highest rate was
      for Cambodians (8.57). This rate compares with rates of approximately 6 for
      Koreans, Thai, and Vietnamese. These rates are similar to those found in Asia but
      lower than those for Californian Chinese, Japanese, and Filipinos, who have been
      established in the state for longer. In general, the results provide support for
      previous reports that twinning rates are modified by both migration and
      interethnic mixing. Rates for Indians from India were lower than those reported
      from the Indian subcontinent, whereas the twinning rates for Native Americans
      (10.15) and Pacific Islanders (10.60) were similar to the rate for US whites.

PMID- 8543301
TI  - Immunoglobulin levels in populations with low hemoglobin levels: study of five
      tribes of central India.
AB  - Average hemoglobin levels for 424 individuals belonging to 5 tribes of central
      India vary between 10.64 g/dl and 11.30 g/dl among males and between 9.62 g/dl
      and 9.97 g/dl among females. These ranges indicate the poor state of health and
      nutrition in these tribes. Three immunoglobulin levels (IgG, IgA, and IgM)
      measured in a subset of the 424 individuals reveal that immunoglobulin and
      hemoglobin levels are inversely related to some extent. Levels of all three
      classes of immunoglobulins were found to be significantly correlated. This
      suggests that humoral immunity is not impaired even under acute nutritional
      stress.

PMID- 8543302
TI  - In memoriam: Elizabeth Smithgall Watts-Parish (1941-1994).

PMID- 8543303
TI  - Obituary for Eike-Meinrad Winkler (1948-1994).

PMID- 8543304
TI  - Small organism, many challenges.

PMID- 8543305
TI  - The role of microvascular injury in the pathogenesis of cutaneous lesions of
      dermatomyositis.
AB  - Although microvascular injury has been postulated as the pathogenetic basis of
      skeletal muscle injury in dermatomyositis (DM), its role in the genesis of the
      skin lesions, which are said to be difficult to distinguish light microscopically
      from systemic lupus erythematosus (SLE) and subacute lupus erythematosus (SCLE),
      has not been analyzed. The authors' intention was to assess the role of
      microvascular injury in the pathogenesis of skin lesions in DM, SLE, and SCLE.
      Light microscopic features of biopsies of lesional skin from 20 patients with
      myopathic DM and 11 with amyopathic DM were compared to eight lesional skin
      biopsies from eight patients with SLE and 12 lesional skin biopsies from 12
      patients with SCLE. Vascular density was compared in the three groups using an
      immunohistochemical preparation with an antibody to factor VIII. In 12 biopsies
      from the DM group, and in 19 of 20 lupus erythematosus (LE) specimens, frozen
      tissue was available. An indirect immunofluorescence methodology was used to
      detect C5b-9 deposition, and direct immunofluorescence studies for other
      immunoreactants were performed in standard fashion. Compared with LE, lesions of
      DM showed a greater degree of endothelial injury, vascular ectasia, and vascular
      fibrin deposition; there were no differences between myopathic versus amyopathic
      DM. C5b-9 deposition in vessels was significantly greater in DM than in LE. The
      superficial vascular plexus density was reduced in lesions of DM versus LE
      control groups with the greatest reduction observed in myopathic DM. Epithelial
      injury and mucin was greatest in myopathic DM. Microvascular injury is the
      apparent pathophysiological basis of skin lesions in DM. Careful attention to
      microvascular pathology enables distinction of DM from SLE and SCLE. Indirect
      immunofluorescence testing using a monoclonal antibody to C5b-9 is a valuable
      tool to distinguish DM from LE in biopsies of lesional skin.

PMID- 8543306
TI  - Epstein-Barr virus infection is an early event in gastric carcinogenesis and is
      independent of bcl-2 expression and p53 accumulation.
AB  - Ninety-five cases of adenocarcinoma of the stomach were evaluated for the
      presence of Epstein-Barr virus (EBV) using a sensitive in situ hybridization
      assay targeting Epstein-Barr virus-encoded RNA 1 (EBER1) transcripts. EBER1 was
      detected in 11 of 95 (12%) of cases. When present, the virus was localized to
      malignant epithelial cells and to dysplastic gastric epithelium, but was not seen
      in normal-appearing gastric epithelium or intestinal metaplasia. The EBV DNA was
      monoclonal in all three cases tested by Southern blot analysis of the EBV
      terminal repeat fragment. These findings suggest that the virus was present
      before malignant transformation. The presence of EBV was strongly associated with
      increased numbers of tumor-infiltrating T lymphocytes; however, EBV was not
      associated with prolonged survival. Neither p53 nor bcl-2 were consistently
      detected in the EBV-associated tumors. Specifically, 6 of 11 EBV-positive
      carcinomas had accumulation of p53 protein by immunohistochemical analysis, which
      was similar to the prevalence of p53 accumulation in EBV-negative specimens and
      suggests that EBV infection does not substitute for p53 mutations during
      tumorigenesis. The bcl-2 oncoprotein was expressed in a third of the carcinoma
      specimens tested, but bcl-2 expression did not correlate with the presence of EBV
      or with expression of EBV latent membrane protein 1. In conclusion, EBV infection
      appears to precede malignant transformation in a significant fraction of gastric
      carcinomas, but neither bcl-2 expression nor p53 accumulation appear to be
      consistently associated with the presence of the virus.

PMID- 8543307
TI  - Alterations of the retinoblastoma gene in clinically localized, stage B prostate
      adenocarcinomas.
AB  - Alterations of the retinoblastoma (Rb) tumor suppressor gene and its encoded
      protein have been detected in a variety of malignant neoplasms. The authors have
      evaluated a series of 26 clinically localized stage B prostate adenocarcinomas
      for loss of heterozygosity (LOH) at 13q14 (including the Rb locus),
      rearrangements or partial deletions of the Rb gene, and alterations of Rb protein
      level by quantitative immunohistochemistry. LOH at the Rb locus occurred in 35%
      of the informative specimens. Of the specimens that showed LOH, 33% also had
      decreased or absent Rb protein in tumor cells by quantitative
      immunohistochemistry. In contrast, none of the specimens without LOH showed loss
      of Rb protein. Thus, LOH is correlated with loss of Rb protein. The authors
      conclude that alterations of the Rb tumor suppressor gene occur in a significant
      fraction of stage B prostate adenocarcinomas.

PMID- 8543308
TI  - Interobserver variation in the histopathological assessment of Helicobacter
      pylori gastritis.
AB  - The histopathologic detection of Helicobacter pylori in gastric biopsy specimens
      is considered the gold standard for the diagnosis of H pylori infection. However,
      few studies have addressed the pathologists' reliability to detect the organism
      and to assess the degree of the related inflammatory changes. The objectives of
      this study were to determine the degree of agreement among the findings of four
      gastrointestinal pathologists in the semiquantitative evaluation of H pylori
      infection and gastritis. Three slides from specified areas of the stomach of 99
      patients with and without H pylori infection were stained with the triple stain,
      coded, and examined independently by four pathologists. For each specimen, a
      visual analogue scale graded from 0 (absent/normal) to 5 (maximal intensity) was
      used to score (1) H pylori (2) neutrophils, and (3) atrophy. Data were analyzed
      using kappa-statistics. The kappa-coefficient for the detection of H pylori
      (present vs absent) was approximately .9 (excellent); for the intensity of
      infection, it was considerably lower on the 6-point scale (approximately .61) and
      improved slightly on an amalgamated 4-point scale (approximately .71). The
      agreement on presence or absence of neutrophils was excellent (kappa = .8) in
      antral biopsies and good (kappa = .67) in corpus biopsies. The kappa for the
      semiquantitative scoring of neutrophils was poor on the 6-point scale
      (approximately .43) and fair on the amalgamated scale (approximately .54). The
      interobserver agreement was the poorest in the evaluation of atrophy (presence,
      absence, categories, or group categories) with kappa coefficients varying from
      .08 and .29. This group of pathologists had a high level of concordance on the
      diagnosis of H pylori infection in any particular patient and a high index in the
      assessment of the intensity of infection. The agreement was less in the
      semiquantitative evaluation of active inflammation. When the evaluation concerned
      a loosely defined feature, such as atrophy, there was essentially no agreement
      among the pathologists. This study suggests the need for further assessments of
      pathologists' ability to provide reproducible diagnoses. These results also
      indicate that more stringent criteria for the diagnosis of "soft" histopathologic
      features (such as atrophy) are urgently needed.

PMID- 8543309
TI  - Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in
      malignant fibrous histiocytomas and dermatofibromas as studied by in situ
      hybridization and immunohistochemistry.
AB  - The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was
      studied in eight malignant fibrous histiocytomas (MFH) and in eight
      dermatofibromas (DF) using in situ hybridization methods (ISH).
      Immunohistochemical stainings were also performed using corresponding antibodies
      to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of
      expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed
      similarly both TIMPs, except for osteoclast-like giant cells, which showed a
      distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both
      TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were
      concordant with the results obtained by ISH. The findings suggest that the
      behavior of MFHs and DFs is not directly or solely dependent on the quantity of
      type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might
      represent a chaotic response of malignant cells to increased matrix degradation.
      Alternatively, it may reflect a deranged communication between type IV
      collagenases and TIMPs in malignant tissues.

PMID- 8543310
TI  - Recommendations for the reporting of resected large intestinal carcinomas.
      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 report for common malignant tumors.
      The recommendations for carcinomas of the large intestine are reported herein.

PMID- 8543311
TI  - Granuloma annulare and necrobiosis lipoidica tissue reactions as a manifestation
      of systemic disease.
AB  - Granuloma annulare (GA) and necrobiosis lipoidica (NL) are generally considered
      to be idiopathic cutaneous palisading granulomatous dermatitides. There are
      sporadic reports of such lesions occurring in patients with coexistent systemic
      diseases other than diabetes mellitus. Having encountered 49 patients whose skin
      biopsies showed GA or NL lesions in the setting of extracutaneous disease, the
      authors set out to assess their clinical and histopathological findings to
      determine if any parameters were predictive of underlying systemic disease. Fifty
      two skin biopsies from 49 patients having either GA or NL in whom there was a
      clinical history of an associated systemic disease were analyzed by light
      microscopy. The main systemic disease associations were rheumatologic, endocrine,
      hematologic, infectious, and inflammatory bowel diseases, ANCA positive
      vasculitic syndromes, and sarcoidosis. The clinical and histomorphological
      features were compared with those of a control group of patients whose skin
      biopsies showed GA or NL and in whom there was no history of extracutaneous
      disease. For the systemic disease group, patients were selected either
      retrospectively or prospectively from 160,000 cases accessioned in a 24-month
      period in the dermatopathology databases of Pathology Services, Inc (Cambridge,
      MA) and Central Medical Laboratories (Winnipeg, Canada). All systemic disease
      cases from the former service were analyzed blindly by the second author and from
      the latter service were analyzed blindly by the first author. Patients in the
      control group were obtained retrospectively from the Pathology Services Inc.
      database by the authors. The location of the lesions was atypical in 30 of 34
      biopsies from systemic disease patients with a GA tissue reaction versus 10 of 22
      biopsies of GA in the control group (P = .001). Six of 18 biopsies from patients
      with NL tissue reactions in the systemic disease group showed an atypical
      location, versus only 1 of 9 biopsies of NL from the control group (P = .19). The
      clinical diagnostic considerations were much broader in the systemic disease
      group versus the control group and included vasculitis, panniculitis, and
      connective tissue diseases including morphea in the former. In 22 of 34 GA
      biopsies and 16 of 18 NL biopsies from the systemic disease group, an active
      vasculopathy of leukocytoclastic, granulomatous, or thrombogenic subtypes was
      demonstrable. None of the GA or NL biopsies from the control group showed a
      similar active vasculopathy. An active vasculopathy was predictive of systemic
      disease in patients having either a GA-like or an NL-like tissue reaction (P <
      .001). Fifteen of 34 GA and 7 of 18 NL biopsies in the systemic diseases group
      showed extravascular neutrophilia in contrast to 3 of 22 GA (P = .02) biopsies
      and 2 of 9 NL (P = .33) biopsies in the control group. The finding of an active
      vasculopathy in a skin biopsy specimen showing a GA- or NL-like tissue reaction,
      particularly in the setting of an atypical clinical presentation both with
      respect to the location and appearance of lesions, should prompt consideration of
      an underlying systemic disease, as should extravascular neutrophilia in a skin
      biopsy showing a GA-like tissue reaction.

PMID- 8543312
TI  - Development of the respiratory diaphragm in childhood: diaphragmatic contraction
      band necrosis in sudden death.
AB  - The authors studied the respiratory diaphragm in 50 normally grown infants and
      children aged 1 to 16 years at the time of sudden death. By comparing the weights
      of both costal diaphragm and heart with age and height, the authors found that
      the diaphragm grows proportionately to the body as a whole and to the heart in
      particular. Diaphragmatic contraction band necrosis was found in 15 cases (30%).
      The incidence was similar in subjects dying of asphyxia (five of 21) to that in
      those dying of trauma (five of 20). It was present in two of 15 of those that
      died at once, and 13 of 35 of those who survived for varying periods with or
      without cardiopulmonary resuscitation. Myocardial contraction band necrosis was
      more common than diaphragmatic contraction band necrosis, being present in five
      of 11 of those who died at once, and 16 of 26 of those that survived for a
      period. Among individual subjects, the authors found no correlation of the
      presence of the diaphragmatic lesion with either cause or mode of death. Based on
      a comparison with the morphologically similar myocardial lesion, the
      etiopathogenesis of diaphragmatic contraction band necrosis may concern a local
      catecholamine effect.

PMID- 8543313
TI  - Proliferative characteristics of differentiated cells in familial adenomatous
      polyposis-associated duodenal adenomas.
AB  - The authors have previously shown that duodenal adenomas in familial adenomatous
      polyposis (FAP) patients typically reveal abundant cells with endocrine
      differentiation (ED), Paneth differentiation (PD), and goblet cell
      differentiation (GD). However, the biological significance and proliferative
      potential of these cells is unknown. To study the proliferative properties of
      cells with ED, PD, or GD in FAP-associated duodenal adenomas, the authors used a
      double-labeling immunohistochemical technique to detect simultaneously the
      presence of proliferating cell nuclear antigen (PCNA), and either chromogranin or
      lysozyme in individual neoplastic cells. Adenomatous cells with GD were
      identified morphologically and also evaluated for the degree of PCNA expression
      by immunohistochemistry. Duodenal adenomas and the adjacent nonadenomatous
      epithelium from 10 FAP patients were studied. Cells with ED, PD, and GD were
      present in all adenomas, and constituted 14.1%, 11.6%, and 17.7% of adenomatous
      cells, respectively. The overall proliferative index of nondifferentiated
      adenomatous cells was 33.3%, which was similar to the proliferative index
      obtained for adenomatous cells with GD (31.2%) and nonadenomatous crypt goblet
      cells (34.9%). In contrast, adenomatous cells with ED and PD showed a significant
      decrease in their proliferative potential (P < .001). Only 6.0% and 7.3% of cells
      with ED and PD, respectively, were proliferative. Nonadenomatous crypt endocrine
      and Paneth cells showed no proliferative potential (proliferative index 0%).
      These results suggest that, in the process of proliferation and differentiation,
      specific subpopulations of adenomatous cells attempt to recapitulate the
      biological characteristics of their normal counterparts in the small intestinal
      crypts. Adenomatous cells with ED and PD are hypoproliferative, a finding that is
      consistent with their differentiated phenotype and suggests that these cells may
      not participate as actively in the growth of these lesions.

PMID- 8543314
TI  - Cell kinetic study of thymic epithelial tumors using PCNA (PC10) and Ki-67 (MIB
      1) antibodies.
AB  - We performed an immunohistochemical cell kinetic study with monoclonal antibodies
      to proliferating cell nuclear antigen (PCNA)-PC10-and Ki-67-MIB-1-on 62 thymic
      epithelial tumors, to evaluate whether there is correlation between the
      proliferation indices of the neoplastic epithelial cells and histological
      subtype, stage, and risk of relapse. The 62 cases of thymic epithelial tumors
      were classified as medullary thymoma (4 cases), composite (mixed) thymoma (17
      cases), organoid thymoma (predominantly cortical) (11 cases), cortical thymoma
      (10 cases), well-differentiated thymic carcinoma (18 cases), and poorly
      differentiated thymic carcinoma (2 cases). Labeling indices were expressed as
      percentage of epithelial cells with positive nuclear immunostaining by random
      counting of 1,000 epithelial tumor cells, using an oil immersion 100 x objective.
      PCNA labeling indices were consistently higher than those of Ki-67, and they
      correlated with each other. Well-differentiated thymic carcinoma showed higher
      labeling indices (3.11% +/- 3.53%) by Ki-67 antibody compared with the medullary
      type (0.60% +/- 0.07%) (P < .05) but there were no statistically significant
      differences between the other histological subtypes. Stage IV cases showed higher
      PCNA labeling indices (PCNA: 11.07% +/- 7.35%, Ki-67: 6.86% +/- 5.87%) than cases
      of the other stages (P < .05), but there were no statistically significant
      differences in either labeling index between the other stages. The number of
      patients who relapsed was too small to permit meaningful correlation between
      labeling indices and relapse. Our results indicate that the differences in
      biological behavior of the different histological subtypes of thymic epithelial
      tumors may be in part explained by differences in tumor growth fraction. Analysis
      of a larger group of patients will be required to determine whether proliferation
      fraction as determined by this method can be used to predict outcome in
      individual cases.

PMID- 8543315
TI  - Ovarian small cell carcinoma with K-ras mutation: a case report with genetic
      analysis.
AB  - A rare case of ovarian small cell carcinoma is reported. Laboratory examination
      of a 46-year-old woman with a lower abdominal tumor showed marked hypercalcemia.
      Her condition deteriorated progressively, and she died one month after admission.
      A right ovarian tumor, 8 cm in diameter, metastases to multiple organs, and
      intraperitoneal bleeding were confirmed by autopsy. Microscopically, the small
      tumor cell had rounded nuclei with small distinct nucleoli and a scanty
      cytoplasm. Small cell carcinoma was diagnosed from these histological features
      and the clinical course associated with hypercalcemia. Immunohistochemical
      studies showed positive staining of neuron specific enolase (NSE) and keratin.
      Genetic analysis using DNA extracted from paraffin sections of metastatic lesions
      revealed mutation of K-ras codon 12. Loss of heterozygosity of the p53 and
      adenomatous polyposis coli (APC) genes was not informative. Previous reports have
      shown that ras gene mutations occur in 30% of epithelial ovarian tumors and
      significantly more frequently in mucinous than in other types of ovarian tumors.
      These results suggest that small cell carcinoma is of epithelial origin and may
      have a genetic alteration similar to that of mucinous tumors.

PMID- 8543317
TI  - Crystal-storing histiocytosis associated with lymphoplasmacytic lymphoma
      mimicking Weber-Christian disease: immunohistochemical, ultrastructural, and gene
      rearrangement studies.
AB  - A case of crystal-storing histiocytosis associated with lymphoplasmacytic
      lymphoma is presented. Unlike previous cases, this patient presented with signs
      and symptoms suggestive of Weber-Christian disease. Biopsy of subcutaneous
      nodules showed numerous deposits of crystal-storing histiocytes with
      lymphoplasmacytic cells, the latter exhibiting light chain restriction (lambda
      chain) with a predominance of immunoglobulin (Ig)G heavy chain. Polymerase chain
      reaction (PCR) analysis of CDR-II* region of the immunoglobulin heavy chain locus
      confirmed monoclonality of the lymphoplasmacytic cells in the nodule. Electron
      microscopy showed polygonal-shaped amorphous crystals, characteristic of
      immunoglobulin in the histiocytic cells. Crystal-storing histiocytosis should be
      examined by immunohistochemical and DNA analysis to confirm or exclude the
      possibility of lymphoplasmacytic lymphoma.

PMID- 8543316
TI  - Ultrastructural and biochemical analysis of sperm flagella from an infertile man
      with a rod-dominant retinal degeneration.
AB  - This study examined the ultrastructural morphology and posttranslationally
      modified alpha-tubulin isoforms in the sperm flagella of a patient presenting
      with infertility and retinal degeneration. Clinical evaluation showed impaired
      motility and gross morphological abnormalities of the sperm and a rod-dominant
      retinal degeneration with midperipheral pigment clumping and scattered bone
      spicules. Other neurological indications included delayed neuroelectric
      transmission in the auditory brainstem and a temporal lobe seizure disorder.
      Ultrastructural analysis showed that 46% of sperm axonemes had missing and/or
      misplaced doublets compared with 10% to 12% in control subjects. ELISA analysis
      showed hypoacetylation of alpha-tubulin (30% of control) but normal levels of
      alpha-tubulin tyrosination. Tubulin acetyl-transferase specific activity was also
      30% of control activity. These characteristics may be indicative of microtubule
      instability leading to the pathological consequences described.

PMID- 8543318
TI  - Undifferentiated carcinoma of the parotid gland in a white patient: detection of
      Epstein-Barr virus by in situ hybridization.
AB  - Paraffin sections of an undifferentiated salivary gland carcinoma of
      lymphoepithelioma type, arising in a white (Greek) patient and confirmed by
      immunohistochemistry, were examined for the presence of Epstein-Barr virus (EBV),
      using in situ hybridization to detect EBV-specific EBER1 message. Epstein-Barr
      virus was detected in malignant epithelial cells, but was not found in lymphoid
      stroma or in residual benign salivary epithelium. These results confirm the
      existence of an association between EBV and tumor cells of undifferentiated
      carcinoma of parotid gland. This is the first demonstration of EBV in a salivary
      gland lymphoepithelioma arising in a non-Eskimo, white patient. This finding
      suggests that the association of EBV with undifferentiated salivary gland
      carcinoma may exist in geographic regions remote from Greenland.

PMID- 8543319
TI  - The nuclear channel system in endometrial adenocarcinoma exposed to
      medroxyprogesterone acetate.
AB  - The nuclear channel system (NCS), giant mitochondria and subnuclear glycogen form
      a triad of ultrastructural features observed in normal human endometrial
      epithelium in response to progestational steroids. Both the giant mitochondria
      and subnuclear glycogen have been described in endometrial adenocarcinoma, but
      the NCS has not. This article reports the development of the NCS in
      adenocarcinoma treated with medroxyprogesterone acetate. Previous studies suggest
      that the NCS in normal tissue is a response to the acyl group in the 17-beta
      position of the D-ring of some progestational steroids, such as
      medroxyprogesterone acetate. Medroxyprogesterone acetate was administered to 12
      postmenopausal women with endometrial adenocarcinoma. Hysterectomies were
      performed 8 to 20 days after treatment. Pretreatment specimens were also obtained
      on 8 of the 12 patients. Using standard electron microscopy procedures, light
      microscopy on plastic semithin sections was first used to confirm the presence of
      tumor. Thin sections of malignant endometrium were prepared and evaluated
      ultrastructurally for progestational alterations. Abnormal giant mitochondria and
      subnuclear glycogen were found both before and after treatment. The third element
      of the triad, the NCS, was not observed in any of the available pretreatment
      biopsies, but was seen in three of the treated specimens. Thus it appears that
      the NCS is a response to the given progesterone therapy.

PMID- 8543320
TI  - Erdheim-Chester disease: a case report with immunohistochemical and biochemical
      examination.
AB  - This report describes a 47-year-old man with Erdheim-Chester disease (EC), the
      second case reported in Japan. The patient complained of knee pain, and the
      roentgenogram of the bilateral legs revealed symmetric osteolytic lesions with
      sclerosis of the metaphyseal regions of the long bones. Histological examination
      of the biopsy specimen showed a xanthogranulomatous lesion consisting of
      aggregations of foamy macrophages and Touton-type giant cells.
      Immunohistochemical study of the foamy cells in the lesion showed positive
      reaction to anti-Kp-1, anti-S-100 alpha, beta, anti-neuron-specific enolase
      (NSE), anti-alpha-1-antichymotrypsin, anti-alpha-1-antitrypsin, and anti-lysozyme
      antibodies. Electron microscopy showed many lipid droplets in the cytoplasm, but
      no Langerhans granules. These results suggested that the disease was part of the
      spectrum of histiocytosis but was different from Langerhans cell histiocytosis.
      Biochemical analysis of material extracted from a lesion showed the predominance
      of cholesterol ester. The disease progressed to central diabetes insipidus, and
      the involvement of multiple organs was indicated by a magnetic resonance image.

PMID- 8543321
TI  - Read film with caution.

PMID- 8543322
TI  - Granular cell epulis.

PMID- 8543323
TI  - Diagnostic criteria of molar conditions.

PMID- 8543324
TI  - Single cell protein: a promising dietary substitute.
AB  - Promises and limitations in exploitation of microorganisms for single cell
      protein (SCP) production have been reviewed. Various aspects discussed include
      global protein problem, microbes as potential sources of food and feed with its
      advantages and disadvantages, salient features in selection of microorganisms for
      SCP production, production of SCP from petroleum based hydrocarbons, renewable
      raw materials like agricultural and forestry residues, industrial by-products and
      wastes, nutritional and safety evaluation of SCP, ways of improving SCP
      production, economics of SCP production and the present status of SCP in India.

PMID- 8543325
TI  - Isatin, a putative anxiogenic endocoid, induces memory dysfunction in rats.
AB  - Isatin (2,3-dioxoindole), one of the components of tribulin, which has been
      postulated to function as an endogenous marker of stress and anxiety, was shown
      to induce a dose-related attenuation of learning acquisition in an active
      avoidance test and inhibition of learning retention, or memory, in a step-down
      passive avoidance paradigm and transfer latency in an elevated plus-maze, in
      rats. Earlier studies have indicated that isatin functions as a 5
      hydroxytryptamine (5-HT)3 receptor agonist in its anxiogenic activity in rats and
      is an antagonist at mammalian atrial natriuretic peptide (ANP) receptors. Since 5
      HT3 receptor antagonists and centrally administered ANP have been shown to
      facilitate learning and memory, the observed memory dysfunction induced by isatin
      can be attributed to its receptor activity at 5-HT3 and ANP receptors. The
      investigation also indicates that anxiogenic agents are likely to disrupt memory
      functions.

PMID- 8543326
TI  - Effect of a composite Indian herbal preparation, CIHP(III) on avoidance learning
      during endurance performance of rats.
AB  - A nine week cross over study (5 weeks drug administration and 4 weeks withdrawal)
      was performed to see the effect of a composite Indian herbal preparation (CIHP
      III), viz. Mentat, on avoidance learning during endurance performance of albino
      rats. Runimex, a circular runway was used for this purpose. The number of stimuli
      viz. electrical shock of 10 mv, in drug treated rats at an oral dose of 47.86
      mg/100 g body wt/single dose/day for 5 days were significantly reduced as
      compared to rats not taking any drug. The number of stimuli decreased
      significantly when the drug was started in the control group. No change in
      avoidance learning was observed over the period of 9 weeks in another group of
      rats. Results indicate significant improvement in avoidance learning during
      endurance performance due to the intake of CIHP(III).

PMID- 8543327
TI  - Anti-stress activity of N-phthaloyl gamma-aminobutyric acid in rats.
AB  - The effect of immobilization restraint stress (RS) on some biochemical and
      biophysical parameters in rats and their modulation by N-phthaloyl gamma
      aminobutyric acid (P.GABA) was studied. RS did not affect the levels of serum
      Ca2+, inorganic phosphate, bilirubin, total protein, but caused insignificant
      increase of albumin level and significantly decreased the cholesterol level. This
      RS induced decrease of serum cholesterol level was reversed by prior treatment
      with P.GABA, while the albumin content showed a decrease. RS-induced a
      generalised increase in serum enzyme activity of lactate dehydrogenase (LDH),
      alkaline phsophatase (AIP), serum glutamate pyruvate transaminase (SGPT) and
      serum glutamate-oxaloacetate transaminase (SGOT). P.GABA normalised RS-induced
      increase of LDH and AlP activity, but it further enhanced SGOT and SGPT
      activities. In synaptosomal membranes, RS caused a decrease in clusterization and
      fluidity, but the thickness of the membrane increased as studied by fluorescence
      probes. Prior administration of P.GABA normalised the changes observed in the
      synaptic membrane.

PMID- 8543328
TI  - In vivo and in vitro effects of metabolic hormones on tissue respiration in toad,
      Bufo melanostictus during hibernation and active phase.
AB  - In vivo and in vitro effects of L-T3, L-T4, estradiol, corticosterone,
      epinephrine and norepinephrine were studied on the rate of liver and muscle
      tissue respiration in B. melanostictus during hibernation and active phase under
      natural climatic conditions. Thyroid hormones were found to be calorigenic only
      during the active phase. Estradiol stimulated the respiratory rate directly
      during hibernation and indirectly during the active phase. Adrenal hormones
      invariably increased the respiratory rate of the tissues in all the experiments.
      On the basis of the present findings it can be concluded that the sensitivity of
      the tissues to various hormones is altered during the active phase and
      hibernation. The calorigenic action of thyroid hormones seems to be associated
      with activity-linked energy demand. Direct stimulation of tissue respiration by
      estradiol during hibernation may be of great adaptative significance. Due to
      their temperature-independent calorigenic action, adrenal hormones may be
      considered as emergency hormones for the regulation of the oxidative metabolism
      in the toad.

PMID- 8543329
TI  - Post-exposure radioprotection by Chlorella vulgaris (E-25) in mice.
AB  - Oral administration of an algal mutant C. vulgaris E-25, 1 hr before or
      immediately after exposure to sublethal gamma-rays increased the number of
      endogenous spleen colony forming units (E-CFU). The magnitude of radioprotection
      was dependent on both, the dose of C. vulgaris fed and the time of
      administration. An optimal E-CFU was observed when 500 mg/kg body wt. of C.
      vulgaris was fed 1 hr before or immediately after irradiation. Significant
      recovery was observed in the number of bone marrow cells and the spleen weight.
      LD50/30 for Chlorella pre- and post-treated mice were 8.66 and 9.0 Gy,
      respectively compared to the control value of 7.8 Gy. The dose reduction factor
      (DRF) was 1.11 and 1.15 for pre-treated and post-treated mice respectively.

PMID- 8543330
TI  - Antibiotic sensitivity pattern of various Lactobacillus acidophilus strains.
AB  - Seven L. acidophilus strains were examined for their antibiotic sensitivity
      against various chemotherapeutic agents and all of them were found to be
      sensitive to novobicin, chloramphenicol, ampicillin, erythromycin,
      oxytetracycline and chlorotetracycline, whereas, all were resistant to
      norfloxacin and nalidixic acid. The sensitivity towards remaining antibiotics
      varied among the strains. The results show that cultures should be tested for
      their sensitivity towards commonly used chemotherapeutic agents to eliminate
      starter failure during manufacture of cultured milk products.

PMID- 8543331
TI  - Idiotypic restriction of murine monoclonal antibodies to a defined antigenic
      region of human thyroglobulin.
AB  - In previous studies, we demonstrated that anti-human thyroglobulin (hTg)
      autoantibodies in patients with thyroid disorders exhibit a restricted epitopic
      specificity towards antigenic region II defined by its reactivity with four
      murine monoclonal antibodies (mAb 3, 6, 10, 15). To analyze the relationships
      between epitopic specificity and idiotypic expression of these mAb, two
      polyclonal anti-idiotypic sera were generated in rabbits by immunization with
      F(ab')2 fragments of mAb 3 and mAb 10. These anti-idiotypic preparations (AI 3
      and AI 10) were tested against a panel of hTg-mAb produced in different strains
      of mice (HR BIOZZI and BALB/c). The idiotypic analysis showed that AI 3 and AI 10
      specifically recognized framework-associated idiotopes as well as paratope
      associated idiotopes shared by region II mAb. These results demonstrate that
      specificity for region II was strongly associated with a restricted idiotype
      suggesting a high sequence homology between V regions. In addition, naive BALB/c
      mice immunized with AI 3 or AI 10 produced anti-hTg (Ab3) antibodies that
      recognize region II epitopes. These latter findings reveal that anti-Id contain a
      population of Ab2 beta carrying the internal image of region II epitopes.

PMID- 8543332
TI  - Growth of B cell colonies independent of T cells: a new perspective.
AB  - Growth of human peripheral blood B cells in a B cell colony assay system is a
      useful technique to study the function of B cell biology. In the initial reports,
      T and B cells were admixed in the culture system, prior to which the T cells were
      treated with mitomycin or irradiation to prevent their proliferation. There were
      reports that optimal growth of B cell colonies required T cells to be in contact
      with the B cells. However, we were able to grow B cell colonies physically
      separated from T cells which were placed on a filter. We speculated then that T
      cells contacted B cells via pseudopods through the pores of the filter. We now
      report the growth of B cell colonies independent of T cells and conclude that B
      cell colony growth depends upon a critical number of B cells plated rather than
      on T cell help.

PMID- 8543333
TI  - An enzyme immunoassay for rat soluble MHC class I molecules (RT1a) and the
      release of soluble class I from mitogenically stimulated mononuclear cells.
AB  - Soluble MHC class I antigens can be detected in the serum of humans and various
      animals and appear in the circulation shortly after liver transplantation. The
      precise role of these antigens is currently uncertain, but soluble MHC class I
      may be involved in immunomodulation. We have developed an enzyme linked
      immunosorbent assay for soluble rat MHC class I (RT1a) molecules and monitored
      the kinetics of antigen release following in vitro stimulation of splenic
      mononuclear cells. A 4 day DA splenocyte Con A supernatant provided a source of
      soluble class I antigens and was arbitrarily assigned a concentration of 1000
      units/ml. Ninety six well plates were coated with a rat RT1a-specific mAb (MN4-91
      6) and soluble class I binding was detected using a biotinylated mAb reactive
      with a monomorphic region of the rat MHC class I molecule (OX18) followed by a
      streptavidin-alkaline phosphatase conjugate and substrate. The intra- and
      interassay variations were typically less than 5% and 10% respectively, to give a
      working range for the assay of between 62.5 and 1000 units/ml. Mitogenic
      stimulation led to a progressive increase in soluble class I levels in culture
      supernatants. This assay will be valuable in differentiating recipient and graft
      responses following experimental organ transplantation.

PMID- 8543334
TI  - Selective inhibitory effects of stress hormones on natural killer (NK) cell
      activity of lymphocytes from AIDS patients.
AB  - To examine the potential role of stress hormones in the progression of HIV
      infections, we developed an in vitro model system that investigates the effects
      of cortisol, adrenocorticotropin-releasing hormone (ACTH) and beta-endorphin on
      the natural killer cell activity of lymphocytes from normal subjects and AIDS
      patients. The system employs a 4 hr 51Cr release assay and K562 target cells.
      Direct addition of cortisol (0.05, 0.1, and 0.2 microgram/ml) or ACTH (10(-6) to
      10(-8) M) to the mixture of effector and prelabeled target cells did not produce
      any significant immunoregulatory effects on the NK cell activity of normal
      lymphocytes. Direct addition of beta-endorphin (10(-13) to 10(-17) M) to the
      mixture of effector and prelabeled target cells did not produce any significant
      immunoregulatory effects on the NK cell activity of lymphocytes from normal or
      AIDS subjects. However, cortisol and ACTH significantly inhibited the NK activity
      of lymphocytes from AIDS patients. The selective inhibitory effects of cortisol
      and ACTH in patients with HIV infections are consistent with a model which
      proposes that stress related neurohormones and/or neuropeptides may be involved
      in the progression of HIV infections.

PMID- 8543335
TI  - Induction of IgA B cell differentiation of bone marrow-derived B cells by Peyer's
      patch autoreactive helper T cells.
AB  - The objective of this study was to demonstrate in vitro that bone marrow-derived
      pro/pre-B cells bearing mu mRNA can switch their Ig heavy-chain isotype to that
      of alpha mRNA-expressing B cells after contact with Peyer's patches-derived
      activated autoreactive CD4+ T cells. Bone marrow-derived pro/pre-B cells and
      activated autoreactive Peyer's patch, mesenteric lymph node, or spleen CD4+ T
      cells were co-cultured in the presence of recombinant (r) IL-2, rIL-7, and Con A
      for 3 days. The mixed cultured cells were isolated for preparation of total RNA.
      Dot/slot hybridization, using murine C mu (pu3741) and C alpha (P alpha J558) Ig
      heavy-chain cDNA probes, detected C mu and C alpha Ig heavy-chain mRNA
      transcripts. The magnitude of each mRNA expression was measured
      demsitometrically. In addition, the secreted class-specific Ig contents from the
      co-cultured supernatants were measured. The results indicate that activated
      autoreactive Peyer's patch and mesenteric lymph node CD4+ T cells provide a
      specific Ig heavy-chain switch from mu to alpha (Peyer's patch CD4+ T cells >
      mesenteric lymph node CD4+ T cells) in bone marrow-derived pro/pre-B cells and
      also assist to develop IgA-secreting plasma cells. The alpha heavy-chain switch
      and IgA production do not occur in the presence of activated autoreactive spleen
      CD4+ T cells. These results support the view that autoreactive gut Peyer's patch
      CD4+ T cells, at least, regulate IgA B cell heavy-chain switching and terminal
      differentiation during gut mucosal B cell development.

PMID- 8543336
TI  - Bacterial superantigens induce the proliferation of resting gamma/delta receptor
      bearing T cells.
AB  - We observe that highly purified (> or = 97% pure) gamma/delta T cells isolated
      from normal peripheral blood proliferate to bacterial toxin supperantigens SEA,
      SEB, SED, and TSST-1. MHC class II molecules were necessary and sufficient for
      the recognition of superantigens by gamma/delta T cells because MHC Class II
      deficient B cell line failed to support the proliferation of gamma/delta T cells
      to toxins and murine L cells transfected with HLA-DR but not untransfected cells
      were capable of presenting toxins to gamma/delta T cells. As in the case with
      alpha/beta T cells, bacterial superantigens synergized with PMA in causing the
      proliferation of purified gamma/delta T cells rigorously depleted of accessory
      cells. Together, our findings suggest that gamma/delta T cells recognize and
      respond to bacterial superantigens in a manner similar to alpha/beta T cells.

PMID- 8543337
TI  - The binding of jacalin with rabbit immunoglobulin G.
AB  - Rabbit immunoglobulin G (IgG) was subjected to affinity chromatography on a
      column of jacalin-Sepharose 4B. While the majority of IgG molecules did not bind,
      a small fraction, representing about 25% of the total IgG applied, bound to
      jacalin-Sepharose 4B. The binding of rabbit IgG to jacalin was further evidenced
      by ELISA performed on jacalin coated microtitre plates. While the jacalin
      retained IgG fraction displayed strong binding, the unretained fraction did not
      demonstrate any detectable binding. Upon SDS-PAGE, both the jacalin retained and
      unretained rabbit IgG fractions displayed identical protein profiles. Upon
      protein blotting it was demonstrated that jacalin binding sites were located only
      on the heavy chain of IgG. These results suggest that rabbit IgG molecules are
      heterogeneous with respect to their glycosylation patterns. A small fraction of
      rabbit IgG molecules binds jacalin and the process is probably mediated through O
      linked oligosaccharides present on the heavy chain of IgG.

PMID- 8543338
TI  - Bovine serum albumin preparations enhance in vitro production of tumor necrosis
      factor alpha by murine macrophages.
AB  - Tumor necrosis factor alpha (TNF-alpha) is most commonly produced by macrophages
      stimulated by lipopolysaccharide (LPS). The present study shows that BSA in place
      of FBS in RPMI 1640 medium accelerated the rate of LPS-induced TNF-alpha
      production by resident peritoneal macrophages from BALB/c mice when compared to
      LPS in serum free medium. Using 10 or 100 ng LPS/ml and 100 U IFN-gamma/ml in
      RPMI 1640 medium plus 0.5% BSA, both cytoplasmic TNF-alpha mRNA and TNF-alpha
      precursor and extracellular TNF-alpha production by mouse macrophages were
      increased when compared to stimulation by LPS plus IFN-gamma in medium without
      BSA and FBS. The level of TNF-alpha produced was shown to be related to the BSA
      concentration. Medium containing BSA but no LPS also stimulated macrophages to
      produce TNF-alpha, but BSA's TNF-alpha inducing activity varied among different
      lots and was not blocked by polyclonal antibody to BSA. This effect appeared to
      be associated with the presence of immunoglobulin in BSA products. Confirmation
      that BSA activity was not due to LPS contamination was achieved by testing
      macrophages from LPS-nonresponder C3H/HeJ mice, as well as testing TNF-alpha
      induction in the presence of polymyxin B (10 micrograms/ml), an LPS inhibitor.

PMID- 8543339
TI  - Leukocyte-derived neutrophil chemotactic factor-2 produced by infiltrated
      leukocytes in allergic inflammation model in rats is macrophage inflammatory
      protein-2.
AB  - In the air pouch-type allergic inflammation model in rats, leukocytes collected
      from the pouch fluid 4 h after the antigen challenge produced proteinaceous
      chemotactic factors for neutrophils. The leukocytes from the immunized rats
      produced significantly higher amount of the chemotactic factors than that from
      the non-immunized rats. The major chemotactic factor, leukocyte-derived
      neutrophil chemotactic factor (LDNCF)-2, was purified and found to be identical
      with rat macrophage inflammatory protein (MIP)-2 by N-terminal amino acid
      sequence analysis. Expression of MIP-2 mRNA was higher in the leukocytes from the
      immunized rats than that from the non-immunized rats. Possible roles of LDNCF-2
      (MIP-2) in neutrophil infiltration in the allergic inflammation is discussed.

PMID- 8543340
TI  - IL-3-LA production by mononuclear cells of patients with multiple sclerosis:
      effect of treatment with intravenous immunoglobulins.
AB  - IL-3-like activity (IL-3-LA) is a growth factor that stimulates stem cell
      maturation. We examined the production of IL-3-LA by peripheral blood mononuclear
      cells of 10 patients with relapsing-remitting multiple sclerosis (MS) following
      one year of treatment with intravenous immunoglobulins (IVIG). The results were
      compared with those obtained in 13 age- and sex-matched untreated patients with
      relapsing-remitting MS and in 14 healthy controls. IL-3-LA was assayed using the
      IL-3-dependent 32-D-cl-23 murine cell line. IL-3-LA production was 60% higher in
      untreated MS patients than in healthy controls (134 +/- 19 u/ml and 78.7 +/- 15.9
      u/ml, respectively; p < 0.01), and lower in patients treated with IVIG than in
      untreated patients (101.4 +/- 4.9 u/ml; p < 0.02). IL-3-LA production also
      decreased after incubation of mononuclear cells with IVIG of both untreated MS
      patients and controls. This study indicates a possible beneficial effect of IVIG
      on the immunological status of MS patients.

PMID- 8543341
TI  - Modulation of expression of genes involved in the inflammatory response by
      lipopolysaccharide and temperature in cultured human astroglial cells.
AB  - In bacterial sepsis and meningitis, large concentrations of interleukin-1 beta
      (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) correlate directly with
      morbidity and mortality. This laboratory has reported previously that elevated
      temperature in the physiologic range is associated with down regulation of IL-1
      beta and TNF alpha expression in cultured astroglia after lipopolysaccharide
      (LPS) stimulation. To further investigate the role of elevated temperature in the
      CNS inflammatory response, the effects of LPS and elevated temperature on the
      expression of genes that participate in the inflammatory response were determined
      in cultured transformed human fetal astrocytes and in an astrocytoma cell line.
      The effect of physiologic temperature elevation on cytokine concentrations in
      cerebrospinal fluid (CSF) was also investigated in a rabbit meningitis model. The
      findings indicate that astrocytes express a wide variety of cytokines, growth
      factors, growth factor receptors, and other genes that could play important roles
      in CNS inflammation. Furthermore, temperature elevation in the febrile range can
      lead to alterations in the patterns of expression of many genes involved in the
      inflammatory response of these cells.

PMID- 8543342
TI  - Relativity of an antigenic homology between human interferon-alpha 1 and
      interferon-alpha 2c.
AB  - Analysis of an antigenic relatedness between human interferon (IFN)-alpha 1 and
      IFN-alpha 2 was performed with mapped monoclonal antibodies raised to the
      respective subtypes. Antigenic properties of immunoreactive domains located in
      the N-terminal segments 30-67 of IFN-alpha 1 and IFN-alpha 2 were found distinct
      when compared by neutralization bioassay or ELISA. On the other hand,
      corresponding domains exhibited an unexpectedly high antigenic homology when
      tested by Western blot. We suppose that this relativity in antigenic relation
      lies in the various extent of denaturation of IFN-molecules in bioassay, ELISA
      and immunoblot. Structural differences of tested antigens may be responsible for
      a conformation-determined access of antibodies to the shared epitopes.

PMID- 8543343
TI  - Stability of polypeptide immunoreactants and polyvinyl alcohol as a blocking
      agent on polyester cloth during dry storage.
AB  - During dry storage at 32 degrees C for 70 days, polypeptide immunoreactants
      (rabbit IgG and rabbit antiperoxidase antibody) adsorbed onto polyester cloth
      demonstrated no loss of immunoreactivity. Polyvinyl alcohol of molecular weight
      30,000-70,000 provided a stable blocking capacity on the immunoreactant-adsorbed
      cloth without affecting immunoreactivity. Cloth-based enzyme immunoassay systems
      are suitable for field testing and transportation in the absence of
      refrigeration.

PMID- 8543344
TI  - Staphylococcal enterotoxin is a bovine T cell superantigen.
AB  - Different isoforms of soluble staphylococcal enterotoxins (SE): SEB, SEC-1 and
      SEC-2, were shown to stimulate bovine T cell proliferation, expression of
      cytokine messages, and IgG production. Intact metabolic function of APC was not
      required since peripheral blood mononuclear cells (PBMC), UV-irradiated prior to
      or following incubation with SE, were both capable of presenting SE, while PBMC
      treated with MAbs against MHC II lost the ability to stimulate T cell
      proliferation. SE caused approximately two fold increase of CD4+, and CD8+ T
      cells, but not MHC II+ APC or B cells. This model system suggests that SE
      transduces not only T cell activation signal, but also a non-proliferative signal
      for primary B cells to produce polyclonal IgG. We hypothesize that enterotoxin
      virulence may be in part due to its effect on activating the immune system.

PMID- 8543345
TI  - Induction of systemic and mucosal immune responses following immunization with
      somatostatin-avidin complexes incorporated into ISCOMS.
AB  - Synthetic, biotinylated somatostatin-14 (Somatotropin Release-Inhibiting Factor;
      SRIF) was conjugated to avidin, and the resulting complex incorporated into
      immune-stimulating complexes (ISCOMS). The ISCOMS were used to study the systemic
      and mucosal immune responses induced by parenteral and gastrointestinal
      vaccination. Mice were immunized by intraperitoneal (IP) and intragastric (IG)
      routes and subsequently by either IP or IG secondary immunizations (groups-IP/IP;
      IP/IG; IG/IG). Antigen specific IgG and IgA antibody secreting cells (ASC) from
      the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP's) were studied
      by an enzyme-linked immunospot assay (ELISPOT). Specific proliferative responses
      of spleen cells to avidin and to SRIF were measured. Immunization IP/IP evoked
      the highest serum IgG levels to avidin and to SRIF as well as the highest numbers
      of splenic IgG isotype ASC. The greatest IgA response in MLN and PP's was induced
      by IP/IG immunization. Only marginal mucosal immunity and no splenic cell
      specific proliferative responses were found by IG/IG immunization. These results
      indicate that ISCOMS are an effective delivery system for protein-peptide
      antigens. The ISCOMS system described elicited systemic and mucosal antibody
      immune responses, and primed specific proliferative response when administered
      IP/IG. This offers another approach for the design and delivery of mucosally
      administered peptide vaccines.

PMID- 8543346
TI  - Immunochemical analysis of carcinoembryonic antigen (CEA)-related antigens
      differentially localized in intracellular granules of human neutrophils.
AB  - Subcellular localization and antigenic properties of eight carcinoembryonic
      antigen (CEA)-related proteins (nonspecific cross-reacting antigens, NCAs) in
      neutrophils, including CD66 antigens, were examined with a panel of CD66
      monoclonal antibodies (MAbs), whose specificities were characterized with CHO
      cells expressing CEA gene family recombinant proteins. Intracellular granules of
      neutrophils were isolated by cell lysis followed by centrifugation on a sucrose
      gradient. SDS-PAGE analysis of immunoprecipitates from the granules revealed that
      NCA-95 (CD66c, NCA-50/90) exists predominantly in the azurophil granule-enriched
      fraction. NCA-90 was identified in the same fraction and was suggested to be a
      molecule closely-related to NCA-95. NCA-26 was identified in the specific granule
      fraction together with NCA-160 (CD66a, BGP), and was likely a splicing variant of
      NCA-160. NCA-100 (CD66b, CGM6) was also identified in this fraction. NCA-80, -58
      and -30, which are detectable in culture medium of neutrophils with polyclonal
      anti-NCA-50/90, were not recognized by any of the CD66 MAbs tested. These
      findings indicate that NCA-160, -100, -95, -90 and -26 are the products of the
      CEA gene family and stored separately in azurophil and specific granules. It
      remains to be clarified whether or not the other three secretory antigens, NCA
      80, -58 and -30, are still unknown members of the CEA family.

PMID- 8543347
TI  - New lymphocyte stimulating monocot lectins from family Araceae.
AB  - Three monocot lectins from underground tubers of plants belonging to the family
      Araceae were investigated for their mitogenic potential towards human peripheral
      blood lymphocytes. All the three lectins turned out to be potent mitogens in the
      [3H]-thymidine uptake assay. Gonatanthus pumilus lectin was mitogenic at an
      optimum concentration of 25 micrograms/ml while Alocasia indica and Sauromatum
      guttatum lectins were most effective at a concentration of 50 micrograms/ml. [3H]
      thymidine incorporation studies further revealed that the lectins were T-cell
      mitogens and did not induce any appreciable DNA synthesis in B-enriched
      lymphocytes. The proliferation kinetic studies detected maximum incorporation on
      day 3 and the mitogenic response was shown to be inhibited by asialofetuin in a
      concentration-dependent manner.

PMID- 8543348
TI  - Propagation of Mycobacterium lepraemurium on supplemented minimal medium and its
      experimental pathogenesis.
AB  - The splenic tissue of a mouse experimentally infected with M. lepraemurium
      (Hawaiian strain, M-65) and developing 'rat leprosy', yielded a pure culture of
      an acid - fast bacterium having all the characteristics of M. lepraemurium on
      mineral salt minimal medium supplemented with simple sources of C and N, e.g.,
      NH4 -salts, liquid paraffin, urea, gelatin etc. This could be maintained, by
      serial passages in vitro with good growth. Its indefinite propagation with tissue
      - free washed, small inoculum on complex media including Ogawa medium was
      difficult, and its serial sub-culture was practically impossible. The in vitro
      isolate from supplemented minimal medium could produce pathological lesions in
      mice typical of rat leprosy.

PMID- 8543349
TI  - Clinical manifestations of bancroftian filariasis with special reference to
      lymphoedema grading.
AB  - We report on some aspects of progression of chronic disease and its association
      with acute manifestations with special reference to grades of lymphoedema in
      bancroftian filariasis. These analyses were based on the clinical history and
      clinical findings of 1300 individuals at the time of their first visit to the
      filariasis clinic at a centre in south India. The mean number of
      adenolymphangitis (ADL) attacks in one year was 4.9 +/- 1.7, 5.5 +/- 0.9 and 10.4
      +/- 3.2 in patients with grade I, grade II and grade III lymphoedema
      respectively. The mean duration of oedema was 47.4 +/- 5.9 days, 6.2 +/- 0.5 and
      8.6 +/- 0.9 yr in patients with grade I, grade II and grade III lymphoedema
      respectively. These findings suggest that the progression of lymphoedema from one
      grade to the next in bancroftian filariasis is associated with increased
      frequency of ADL attacks.

PMID- 8543350
TI  - Chloroquine versus amodiaquine in the treatment of Plasmodium falciparum malaria
      in northeast India.
AB  - Amodiaquine is being used in India for presumptive treatment as an alternative to
      chloroquine in areas with chloroquine resistant P. falciparum. Keeping in view
      the toxicity of amodiaquine, studies have been undertaken to evaluate the
      advantage of the drug over chloroquine in the treatment of P. falciparum malaria.
      In vivo drug resistance studies were carried out in the states of Assam and
      Meghalaya in India. A total of 388 subjects have been studied to compare the
      efficacy of chloroquine and amodiaquine. The overall cure rate, degree of
      resistance, mean parasite clearance time and mean parasite recrudescence time
      were comparable for both the drugs, the differences being not statistically
      significant. The results indicate no advantage of amodiaquine in the treatment of
      patients with P. falciparum infection in chloroquine resistant areas of northeast
      India and development of cross resistance in P. falciparum to these 4
      aminoquinolines is complete and parallel.

PMID- 8543351
TI  - Studies on the life cycle of Artyfechinostomum oraoni Bandyopadhyay, Manna &
      Nandy 1989: embryogenesis & development in the intermediate host.
AB  - A study was undertaken to elucidate the life cycle of the parasite A.oraoni,
      isolated from man. For the purpose, operculated eggs were isolated from faeces of
      oraon tribals belonging to the village Bandipore, district North 24-Parganas of
      West Bengal province of India. The purified eggs were incubated at different
      temperatures, salinity and pH. Larvae (miracidia) could be observed to develop
      between the 7th and 8th day of incubation at a temperature range between 22
      degrees-30 degrees C. While the optimum pH was observed to be neutral, larval
      development did not take place at salinity beyond 0.8 per cent. To identify the
      correct intermediate host, all available species of snails from the study village
      were colonised and infected with the laboratory hatched miracidia from human
      derived operculated eggs. It was observed that of all the snails infected, only
      Lymnaea supported the development of rediae from miracidia, which could be
      observed on the 32nd post infection day. Considering the results of the
      experimental study, it was hypothesised that Lymnaea spp. of snails under natural
      condition also, might act as the first intermediate host for A. oraoni.

PMID- 8543352
TI  - Immunogenicity of low dose hepatitis B vaccine by the intradermal route &
      persistence of anti-HBs after three years.
AB  - Plasma derived hepatitis B vaccine given intradermally (0.2 ml; 4 micrograms
      HBsAg) at 0, 1, 6 months to 200 health care workers, produced seroconversion in
      97.5 per cent. Antibody levels to hepatitis B surface antigen (anti-HBs) crossed
      1000 mIU/ml in 62 per cent while 26.5 per cent had levels of 100 to 1000 mIU/ml.
      Anti-HBs levels persisted in the same range in 41.7 per cent but dropped by a log
      in 58.3 per cent subjects at the end of 3 yr. Protective antibodies above 10
      mIU/ml were documented in 93.3 per cent vaccinees after 3 yr. The 0.2 ml vaccine
      by intradermal (id) route was also found to give a good booster effect in another
      group of 27 persons who had received full dose vaccine 5 yr earlier. Thus, 0.2 ml
      vaccine by id route was safe, gave high seroconversion and persistent antibody
      levels over 3 yr and could offer effective protection at an economic cost.

PMID- 8543353
TI  - The effect of lethal endotoxaemia on the liver glycogen metabolism in guineapigs
      with common bile duct obstruction.
AB  - The effect of hepatocellular trauma due to bile reflux and endotoxaemia on liver
      glycogen metabolism was studied in guineapigs with common bile duct obstruction.
      Considerable drops in basal glycogen levels of hepatocytes from bile duct ligated
      (BDL) animals were recorded in comparison with the sham operated (SHAM) ones.
      However, the regurgitation of bile did not affect the basal blood glucose
      concentrations of BDL guineapigs. The circulating glucose was consumed, mainly
      reflecting the level of energy requirement of the peripheral tissues in the
      endotoxaemic SHAM pair-fed animals and the BDL group. The hepatic glycogen stores
      failed to prevent the SHAM group from becoming hypoglycaemic at the end of the
      eighth hour after endotoxin administration. Enhancement in glucose consumption
      and diminished liver glycogen indicated the necessity of glucose intake in the
      early phase of extrahepatic bile duct obstruction. It was concluded that both
      endogenous and exogenous glucose have limited value in improving energy
      metabolism in lethal endotoxaemia following bile duct obstruction.

PMID- 8543354
TI  - Dustiness, silicosis & tuberculosis in small scale pottery workers.
AB  - Studies were carried out in eight small scale potteries to find out the airborne
      dust concentrations and the prevalence of dust related diseases like silicosis
      and tuberculosis in 292 workers. Chest radiography revealed that 44 (15.1%)
      pottery workers were suffering from silicosis and an equal number showed
      radiological evidence of tuberculosis. The environmental study showed that the
      concentrations of airborne dust, containing free silica, in the work environment
      of all departments (except packing department) of potteries were higher than
      threshold limit values (TLVs). The prevalence of silicosis and tuberculosis
      correlated with the levels of airborne dust. The prevalence of tuberculosis
      increased with radiological severity of silicosis. Dust control measures combined
      with pre-employment and periodical medical examinations are recommended for the
      control of silicosis and tuberculosis in the pottery industry.

PMID- 8543355
TI  - Combined immunosuppressive therapy in aplastic anaemia.
AB  - Fifteen patients with aplastic anaemia (AA) were treated combined
      immunosuppressive treatment (9 of them had severe, the others had less severe
      AA). Cyclosporin A(CsA) was given as 12 mg/kg/daily intravenous infusions for 90
      days with serum levels being monitored weekly by radioimmunoassay. Antilymphocyte
      globulin serum (ALG) was administered by intravenous infusion through eight hours
      at a dosage of 20 mg/kg/daily for eight days. Methylprednisolone (MP) was given
      orally as 5 mg/kg/daily, tapered every three days, for 29 days. Complete
      remission (CR) was observed in five severe AA patients and two less severe AA
      patients with therapy. Partial remission (PR) was observed in one severe AA and
      two less severe AA patients. No remissions were reached in four patients, two of
      whom had severe AA, the others had less severe AA. Replace was observed in two
      patients as sixth and ninth month. Haemolysis occurred in one patient and MP was
      started. Only one patient died during the treatment because of infection due to
      febrile neutropaenia. Toxicities were reversible. Combined immunosuppressive
      treatment may be the treatment of choice for patients who are not eligible for
      bone marrow transplantation.

PMID- 8543356
TI  - Isolation of tubercle bacilli from sputum samples of patients in the field
      studies by the cetylpyridinium chloride-sodium chloride & sodium hydroxide
      methods.
AB  - A total of 125 sputum specimens, collected in the field, were homogenised,
      aliquoted in sterile universal containers and randomly allocated to the
      cetylpyridinium chloride - sodium chloride (CPC-NaCl) method and sodium hydroxide
      (NaOH) method for culture of tubercle bacilli. After storage for 8 days at
      ambient temperature in the field laboratory at Thiruvallur, the aliquots were
      transported to the main laboratory at Madras where they were processed for
      culture by the respective methods. The yield of positive cultures in the CPC-NaCl
      (31/125) method was only marginally better than that in the NaOH method (27/125)
      (95% CI being-3.4 to 9.8%), while the contamination of cultures was significantly
      less in the CPC-NaCl method (3/125) than in the NaOH method (12/125) (95% CI
      being 2.2 to 12.2%). As the CPC-NaCl method has advantages over the NaOH method
      in reducing contamination, in augmenting the yield of positive cultures and also
      in its simplicity, it can be applied in field studies.

PMID- 8543357
TI  - Vancomycin for controlling contamination of selective Kirchner's liquid medium in
      the culture of gastric lavage for tubercle bacilli.
AB  - Gastric lavage (GL) was collected for culture of tubercle bacilli from children
      too young to expectorate sputum. The selective Kirchner's liquid medium (SKLM),
      routinely used as one of the media for culture of all extrapulmonary specimens,
      was found to often get contaminated when cultured with GL. We have shown that
      vancomycin at a concentration of 10 mg/l successfully reduced the contamination
      from about 60 to 20 per cent, and enhanced the isolation rate of tubercle bacilli
      from 3 to 6 per cent. Decontamination of the liquid culture before subculture on
      solid medium also helped to reduce the contamination rate. Vancomycin was found
      to be an effective selective drug for use in the Kirchner's liquid medium for
      culture of tubercle bacilli.

PMID- 8543358
TI  - Rapid identification of colonization factor antigens I & II of enterotoxigenic
      Escherichia coli by coagglutination test.
AB  - Specific antisera for colonization factor antigens (CFA/I and CFA/II) were
      adsorbed to Staphylococcus aureus Cowan I strain, ATCC 12598 to make
      coagglutination (CoA) reagents for detection of CFAs in enterotoxigenic Esch.
      coli (ETEC) isolates. Among 1782 strains of Esch. coli isolated from patients
      with acute diarrhoea, 238 (13.4%) strains exhibited CFA expression. Most
      prevalent CFA/I positive serogroups were 015, 0148, 0153, 020, 0128, 0114 and
      078. CFA/II was detected among isolates of serogroup 080, 085, 06 and 08. Ten
      ETEC isolates each of serogroups 04, 07, 061, 068, 0117 and 0158 did not show
      presence of CFA/I or CFA/II. CoA technique proved an appropriate, rapid
      diagnostic tool which can be used for screening large number of Esch. coli
      isolates in epidemiological studies.

PMID- 8543359
TI  - Utilization of used human immunodeficiency virus ELISA microplates & surplus
      reagents for HIV antibody testing.
AB  - Used non-competitive enzyme-linked immunosorbent assay (ELISA) microplates were
      washed and reused to test samples and positive and negative controls, utilising
      the surplus reagents provided with the kit, which otherwise would have been
      discarded as useless after the entire 960 test kit had been utilized. These
      surplus reagents could be used for additional 220 tests over and above the
      recommended 960 tests per kit. A total of 839 unknown serum samples, 54 negative
      controls and 36 positive controls were tested using both washed and fresh (new)
      ELISA plates simultaneously. The optical density (OD) value of the control sera
      was within the prescribed limits in both the methods and 15 samples were found to
      be positive for HIV antibodies by the fresh plates whereas the washed plates
      showed 18 samples to be positive for HIV antibodies. None of the samples positive
      by fresh plates were negative by washed plates.

PMID- 8543360
TI  - Prevalence of hepatitis C virus antibodies in the general population & in
      selected groups of patients in Delhi.
AB  - We report on the prevalence of anti-HCV antibodies in healthy individuals and
      patient groups with different liver diseases. The healthy population comprising
      234 voluntary blood donors and 65 pregnant women with no history of liver
      diseases, had a per cent positivity of 1.5 anti-HCV in each group. The patients
      groups comprising 32 with acute viral hepatitis, 110 with fulminant hepatic
      failure, 65 with subacute hepatic failure, 33 with chronic active hepatitis, 45
      with cirrhosis and 10 with hepatocellular carcinoma, had anti-HCV per cent
      positivity of 12.5, 43.6, 41.5, 48.5, 8.8 and 0 respectively. Anti-HCV was also
      tested in sera from 9 patients who had developed post-transfusion hepatitis and
      was recorded in 2 (22.2%) within one year of transfusion.

PMID- 8543361
TI  - Recent kala-azar cases in India: isozyme profiles of Leishmania parasites.
AB  - In this study, three WHO recommended reference strains of Leishmania donovani
      (DD8), L. tropica (K27) and L. major (5 ASKH) were compared by isozyme analysis
      of 9 soluble enzymes using cellulose acetate electrophoresis (CAE). The isozyme
      profile of the three species showed distinct electrophoretic mobilities of the
      enzymes studied. This technique was applied to study the enzyme patterns of 8
      clinical isolates of visceral leishmaniasis (VL) and two post kala-azar dermal
      leishmaniasis (PKDL) collected from the present epidemic (1990s to date). They
      were seen to be similar to the two isolates of the 1970s epidemic. Interspecies
      differences were observed in different reference Leishmania species whereas no
      intraspecies difference was observed amongst the clinical isolates (8VL + 2PKDL)
      and all of these were found to be similar to L. donovani isolates of 1970s
      epidemic.

PMID- 8543362
TI  - Feasibility of Broka's index for the nutritional status of adults.
AB  - The utility and feasibility of Broka's index for assessing the nutritional status
      of adults was studied in comparison with the efficacy of weight for height (%)
      and body mass index (BMI). The coefficients of correlation, sensitivity,
      specificity and efficiency and Kappa statistic for agreement were determined and
      tested for significance. The data pertaining to urban adults of Hyderabad
      belonging to better socio-economic class were utilised. Broka's index was well
      correlated with weight for height (%) (r = 0.97) and BMI (r = 0.99). Broka's
      index, BMI and weight for height (%) were least correlated with stature
      indicating that these indices were of use for classifications of nutritional
      status irrespective of variations in stature. There was a good agreement between
      classifications of nutritional status based on Broka's index, weight for height
      (%) and BMI. The values of sensitivity, specificity and efficiency were in the
      range of 90-100 per cent. The Kappa statistic of agreement between Broka's index,
      BMI and weight for height (%) for all forms of nutritional status was 0.839 (P <
      0.0001). The mean values of Broka's index, BMI and weight for height (%) were
      higher in the better socio-economic group as compared to the poor ones. Broka's
      index which is simple and easy to calculate is useful for the assessment of the
      grades of body built and nutritional status in adults.

PMID- 8543363
TI  - Heart rate & blood lactate response in amateur competitive boxing.
AB  - The heart rate (HR) and blood lactate response were studied on 26 senior national
      level boxers in competitive bouts to explore the aerobic-anaerobic metabolism as
      well as the training status of the players. The aerobic capacity (VO2 max) of the
      players were determined using graded running protocol on a treadmill. Heart rate
      and blood lactate concentration were measured during warm up and boxing rounds.
      The mean relative VO2 max of the heavy weight category boxers was lower (P <
      0.05) than the other two weight categories. No interweight category as well as
      inter-round differences were observed in the heart rate and blood lactate
      concentration of the boxers, excepting in the 48-57 kg category, the mean lactate
      levels in the second and third rounds were higher (P < 0.05) than in the first
      round. When all weight categories were pooled the mean HR and blood lactate
      levels were 178 beats/min and 8.24 mMol/l respectively. The study highlights that
      in amateur boxing, irrespective of the weight category and aerobic capacity, the
      anaerobic adaptability of the boxers was the same. The training requirements of
      the boxers demand that they should be also to tolerate a high blood lactate level
      (approx. 9.0 mMol/l) and a high HR (approx. 180 beats/min) over a total duration
      of one bout.

PMID- 8543364
TI  - Haematological & histological studies after curry leaf (Murraya koenigii) &
      mustard (Brassica juncea) feeding in rats.
AB  - Whole curry leaf and mustard fed to rats at doses equal to normal human intake
      did not cause any adverse effect on food efficiency ratio (FER), red blood cell
      count (RBC), white blood cells (WBC), total count, differential counts or on the
      levels of blood constituents, like serum electrolytes, blood urea, haemoglobin,
      total serum protein, albumin-globulin ratio, fibrin level, glycosylated
      haemoglobin and the activity of glutamic oxaloacetic transaminase (GOT), glutamic
      pyruvic transaminase (GPT) and alkaline phosphatase in serum. No
      histopathological changes were observed in the liver of rats administered curry
      leaf and mustard.

PMID- 8543365
TI  - A direct rifampicin sensitivity test for tubercle bacilli.
AB  - A direct sensitivity test for rifampicin has been standardised for early
      detection of resistance for the mycobacterium tuberculosis smear positive sputum
      samples. Indirect sensitivity tests set up from primary cultures of the same
      samples served as controls. The direct test showed 95 per cent agreement with the
      standard indirect test and as such 74 per cent and 90 per cent of the resistant
      strains were detected by the fourth week and fifth week, respectively, with an
      overall gain of 4-5 wks time. Resistance could be detected earlier for
      multibacillary specimens. This direct sensitivity test on Lowenstein Jensen (LJ)
      medium offers a feasible alternative for laboratories which lack facilities to
      perform drug susceptibility tests by the rapid but sophisticated and costly
      BACTEC method. The method is simple to perform, economic, reliable and amenable
      to confirmation by the indirect test, if needed.

PMID- 8543366
TI  - Pharmacological activity of the second generation leukotriene B4 receptor
      antagonist, SC-53228: effects on acute colonic inflammation and hepatic function
      in rodents.
AB  - Inflammatory bowel disease is a chronic inflammatory disorder of the
      gastrointestinal tract that includes ulcerative colitis and Crohn's disease.
      Leukotriene B4 is thought to be a prominent proinflammatory mediator in these
      diseases, in that leukotriene B4 levels are increased in the colonic mucosa of
      inflammatory bowel disease patients and there is increased polymorphonuclear
      leukocyte infiltration of these tissues. SC-53228 [(+)-(S)-7-[3-[2(
      cyclopropylmethyl)-3-methoxy-4- [(methylamino)carbonyl]phenoxy]propoxy]-3,4
      dihydro-8-propyl-2H-1- benzopyran-2-propanoic acid], a second generation LTB4
      receptor antagonist, was evaluated for therapeutic efficacy in a rodent model of
      acute colonic inflammation induced by short chain organic acids, as well as for
      effects on rodent liver. When given intracolonically to mice, SC-53228 inhibited
      neutrophil infiltration, assessed by myeloperoxidase (MPO) levels, with an ED50
      value of 9 +/- 1.2 mg/kg. When given by gavage, SC-53228 inhibited neutrophil
      influx in colitic mice with an ED50 value of 30 mg/kg. These results were also
      confirmed histologically. Furthermore, high dose oral SC-53228 treatment had no
      effect on liver cytochrome P-450 content, fatty acyl CoA oxidase or liver weight
      in rats and mice. Together, these data suggest that SC-53228 may be efficacious
      orally and locally, as well as safe for use in trials for the medical management
      of IBD.

PMID- 8543367
TI  - Monocyte adherence to the subendothelial basement membrane increases interleukin
      8 gene expression and antigen release.
AB  - The emigration of peripheral blood monocytes into the interstitium allows for
      contact with a variety of surfaces which may provide signals important for
      monocyte function in both normal and inflammatory states. In the present study,
      we examined the effect of adherence to an endothelial cell-derived basement
      membrane and to collagen I, the major collagen of the interstitium, on monocyte
      release and gene expression of the potent chemotactic cytokine Interleukin-8 (IL
      8). We further evaluated neutrophil chemotactic activity of the conditioned media
      containing antigenic IL-8 from monocytes adherent to these same surfaces.
      Elutriation-purified monocytes were adhered for 1 hour to plastic tissue culture
      wells either uncoated (PL) or coated with bovine serum albumin (BSA), collagen
      type I (C-I), or endothelial cell-derived basement membrane (BM). Following
      removal of nonadherent cells, monocytes were further incubated in a serum-free
      media for 18 hours in the presence or absence of lipopolysaccharide (IPS).
      Following 18 hrs of incubation there were significantly less monocytes remaining
      adherent to BM when compared to other surfaces tested. In the absence of LPS,
      adherent monocytes released significant amounts of IL-8 that was not surface
      specific. In the presence of LPS, monocytes adherent to BM released significantly
      more IL-8, when corrected for adherent cell number, than monocytes adherent to
      PL, BSA, or C-I. Conditioned media from adherent monocytes expressed IL-8
      dependent neutrophil chemotactic activity that was not influenced by the surfaces
      tested. Northern blot analysis indicated greater induction for IL-8 mRNA by
      monocytes adhered to BM after 18 hrs in the presence of LPS. These results
      suggest that monocyte adherence to the subendothelial basement membrane provides
      a priming signal for the induction and secretion of the chemotactic cytokine IL-8
      in response to inflammatory stimuli.

PMID- 8543368
TI  - The increased potential for the production of inflammatory cytokines by Kupffer
      cells and splenic macrophages eight days after thermal injury.
AB  - Burn patients often experience a devastating inflammatory response to infection
      within the first two weeks after thermal injury. The inflammatory cytokines IL-6,
      TNF and IL-1 have been implicated in this condition but most studies have focused
      on the abnormal levels of cytokines in the plasma. In this study the production
      of cytokines was compared for Kupffer cells versus splenic macrophages; endotoxin
      (LPS) stimulation versus no stimulation; and burn (post burn days 1, 3 and 8)
      versus no burn (control). Corresponding serum levels of IL-6 were also
      determined. Kupffer cells from normal or burned animals were shown to produce
      much higher amounts of the inflammatory cytokines than that produced by splenic
      macrophages. An exception to this was the equal production of TNF by LPS
      stimulated hepatic and splenic cells. Both LPS-stimulated Kupffer cells and
      splenic macrophages produced larger amounts of the cytokines than that produced
      by the unstimulated cells. There was a significant effect of thermal injury on
      cytokine production by LPS-stimulated Kupffer cells at post burn day 8 and on TNF
      production by stimulated splenic macrophages also at post burn day eight.
      Although there was a statistically significant effect of thermal injury at post
      burn day 8 on IL-1 production by unstimulated splenic macrophages, the absolute
      amount of cytokine produced was very small. The results suggest that by post burn
      day 8 the cells may have become primed to respond to a stimulus such as endotoxin
      (LPS), a condition that could arise in a burn patient from sepsis. Strangely, the
      large spike in serum IL-6 level occurred at post burn day one and the level of
      the cytokine returned nearly to the control value on post burn days 3 and 8.

PMID- 8543369
TI  - Up-regulation of antigens on alveolar macrophages in quartz exposed rats.
AB  - We have analysed the expression of the OX-6 and OX-42 antigens on alveolar
      macrophages in rats after intratracheal exposure to quartz. Eight female Sprague
      Dawley rats were included in the study. Four were exposed to physiological saline
      and four to quartz dust. The rats were sacrificed after 58 +/- 2 weeks and
      alveolar macrophages were harvested and analysed by flow cytometry. We found a
      significant higher amount of both antigens on alveolar macrophages harvested from
      quartz exposed rats. However, we did not find any significant difference in the
      percentage positive labeled cells between the two groups. We conclude that quartz
      dust induces up-regulation of functional receptors on alveolar macrophages in
      rats and that quantitative analysis of these receptors may serve as inflammatory
      markers in the bronchoalveolar space.

PMID- 8543370
TI  - Interleukin-1 beta induces expression of cyclooxygenase-2 mRNA in human gingival
      fibroblasts.
AB  - The effect of interleukin-1 beta (IL-1 beta) on the expression of cyclooxygenase
      1 and -2 (COX-1 and COX-2) mRNA and its relation to prostaglandin E2 (PGE2)
      biosynthesis in human gingival fibroblasts was studied. IL-1 beta increased
      levels of mRNA for COX-2 whereas the COX-1 mRNA level was unaffected. The
      increased COX-2 mRNA levels were accompanied by enhanced PGE2 formation. The
      phorbol, 12-myristate 13-acetate (PMA), known to stimulate protein kinase C
      (PKC), also induced expression of COX-2 mRNA. When gingival fibroblasts were
      treated simultaneously with IL-1 beta and PMA, the cytokine IL-1 beta
      synergistically increased levels of COX-2 mRNA, accompanied by a corresponding
      increase in PGE2 biosynthesis. The anti-inflammatory steroid, dexamethasone (DEX)
      abolished the enhanced expression of COX-2 mRNA as well as PGE2 formation induced
      by IL-1 beta, PMA or the combination of IL-1 beta and PMA. The study indicates
      that the IL-1 beta induced PGE2 formation is mediated by an enhanced gene
      expression of COX-2 in gingival fibroblasts suggesting that the enzyme COX-2 may
      play an important role in the regulation of prostanoid formation at inflammatory
      lesions in gingival tissue.

PMID- 8543371
TI  - Inhibition of neutrophil chemotaxis by protease inhibitors. Differential effect
      of inhibitors of serine and thiol proteases.
AB  - Previous studies have demonstrated that neutrophils possess an active serine
      protease(s) which may be involved in the process of chemotaxis but the precise
      identity of this enzyme(s) remains to be determined. In this study fourteen
      different protease inhibitors were tested over a wide concentration range for
      their ability to inhibit unstimulated neutrophil movement and chemotaxis to C5a,
      fMLP and IL-8. Pretreatment of neutrophils with aspartyl or metallo-protease
      inhibitors had no effect on either chemotaxis or random cell movement. The thiol
      protease inhibitors E-64 and cystatin, as well as the thiol/serine inhibitors
      antipain and leupeptin, diminished only C5a-induced chemotaxis. Pretreatment of
      neutrophils with the serine protease inhibitors PMSF or 3,4-DCI significantly
      reduced chemotaxis to C5a, fMLP and IL-8. The inhibitor of trypsin-like serine
      proteases, TLCK, and the neutrophil elastase inhibitor MeO-Suc-AAPV-CMK had no
      inhibitory effect on cell movement. However, two different inhibitors of
      chymotrypsin-like serine proteases, TPCK and chymostatin, significantly inhibited
      movement to any chemoattractant. These results suggest that an active
      chymotrypsin-like serine protease is essential for neutrophils to respond to
      chemotactic stimuli.

PMID- 8543372
TI  - Cytokine-induced neutrophil chemoattractant production by primary rat alveolar
      type II cells.
AB  - This study was designed to determine the production of the chemokine cytokine
      induced neutrophil chemoattractant (CINC) by primary rat alveolar type II (ATII)
      cells upon stimulation with exogenous and endogenous proinflammatory factors.
      Cultures of primary rat ATII cells were exposed to lipopolysaccharide (LPS),
      interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF alpha) over a
      16 hour period and the production of CINC both apically and basolaterally was
      measured by ELISA. Compared to unstimulated (UNS) cultures, LPS, IL-1 beta and
      TNF alpha were found to significantly increase the level of CINC detected in
      culture by two, four and sixteen hours post stimulation, respectively. ATII cells
      also demonstrated a polar secretion of CINC. The accumulation of CINC
      basolaterally was significantly more than apically; 133%, 45%, 117% and 123% for
      UNS, IL-1 beta, LPS and TNF alpha respectively. We demonstrated that primary rat
      ATII cells may participate in the chemokine network during inflammation by the
      production of CINC upon stimulation with endogenous and exogenous factors.

PMID- 8543373
TI  - Nitric oxide and interleukin-8 as inflammatory components of cystic fibrosis.
AB  - We examined the production of reactive nitrogen intermediates in the tracheo
      bronchial tree of patients with cystic fibrosis (CF). Examination of the soluble
      phase of sputa from 17 CF patients revealed the presence of high levels of NO2
      /NO3- assayed by the Greiss reaction. We also examined the presence of the
      chemotactic cytokine interleukin-8 (IL-8) in these samples so as to assess
      another important inflammatory marker; high levels of IL-8 were present in the
      sputa of cystic fibrosis subjects. The elevated nitrite was not produced by the
      presence of Pseudomonas bacteria in the sputa, inasmuch as bacteria in culture
      released undetectable amounts of nitrite in culture media. Neutrophils from the
      sputa of CF patients with disease exacerbation released higher amounts of nitrite
      and IL-8. Neutrophils from the sputa were also shown to spontaneously release
      substantial amounts of nitrite in the supernatants, and this release was partly
      blocked by the antagonist NG-mono-methyl-L-arginine (L-NMMA). Blood neutrophils
      were shown to release nitrite only in response to challenge with CF-associated
      strains of Pseudomonas, and not exposure to cytokines. There was no significant
      differences in nitrite release between normal and CF blood polymorphonuclear
      leucocytes (PMNs). A study of upper airway epithelial cell lines showed that
      these cells released low amounts of nitrite after infection with CF-associated
      strains of Pseudomonas but not after cytokine exposure. Epithelial cell lines
      with CF or normal phenotypes were shown to release similar quantities of nitrite,
      upon stimulation with Pseudomonas. These data demonstrate that elevated levels of
      reactive nitrogen intermediates and IL-8 are produced in the tracheo-bronchial
      tree of subjects with CF. Levels of IL-8 and nitrite were higher in the
      secretions of CF subjects with disease exacerbation. The involvement of nitric
      oxide and other reactive nitrogen intermediates produced by neutrophils and other
      cells in the tissue damaging processes in CF deserves further investigation.

PMID- 8543374
TI  - The involvement of nitric oxide in a mouse model of adult respiratory distress
      syndrome.
AB  - The release of free radicals and pro-inflammatory cytokines such as nitric oxide
      (NO) and tumor necrosis factor alpha (TNF alpha) is commonly observed in adult
      respiratory distress syndrome (ARDS) following infection or exposure to microbial
      products. The aim of this study was to scrutinize the involvement of NO in ARDS
      in a mouse model determined by the sequential exposure to lipopolysaccharide
      (LPS) and formyl-norleucyl-phenylalanine (FNLP). Nitrite measurements in
      bronchoalveolar lavage fluids (BALF) and sera demonstrated that exposure to
      microbial products elicits large amounts of NO in LPS/FNLP-challenged mice. This
      release was significantly inhibited by infusion with the inducible NO synthase
      antagonist, aminoguanidine (AG). Our results show that LPS/FNLP exposure induces
      lung damage as demonstrated by protein and lactate dehydrogenase (LDH) increases
      in BALF. Liver damage was also detected in LPS/FNLP-challenged mice with
      increases in serum ornithine-carbamoyltransferase (OCT) levels. LPS/FNLP infusion
      led to elevated levels of the cytokines interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF alpha) in the sera. LPS/FNLP also led to neutrophil adhesion in
      the lung vasculature, as seen by increased levels of myeloperoxydase.
      Interestingly, inhibition of NO release in challenged mice led to an important
      increase in markers of tissue damage in the lungs and livers, but a decrease in
      neutrophil recruitment. Infusion of AG in LPS/FNLP-challenged mice led to a much
      increased level of sera TNF alpha. These data suggest that after exposure to
      microbial products, NO generated as a result of activation of the inducible NO
      synthase blocks the full expression of tissue damage in the lungs.

PMID- 8543375
TI  - "Marriage to a smoker" may not be a valid marker of exposure in studies relating
      environmental tobacco smoke to risk of lung cancer in Japanese non-smoking women.
AB  - There is no direct evidence that workplace environmental tobacco smoke (ETS)
      increases lung cancer risk. Demands for regulation of workplace smoking are based
      on studies reporting increased risk in non-smoking women whose husbands smoke.
      Although denying smoking can artificially elevate risk estimates, and although
      many studies reporting an increase have been conducted in Asia, no previous study
      of smoking habit misclassification has been conducted there. In this study 400
      married Japanese women answered questions on smoking and ETS exposure and
      supplied urine for cotinine analysis. Of 106 with a cotinine/creatinine ratio
      (CCR) indicating current smoking (> 100 ng/mg), 22 reported never smoking. These
      misclassified smokers had a median CCR (1408 ng/mg) similar to the 78 self
      reported current smokers (1483 ng/mg). Of current smokers, 89.7% had a currently
      smoking husband, while this was true of 51.0% of non-smokers. Among 264 confirmed
      non-smokers (with CCR < 100 ng/mg), CCR was non-significantly lower if the
      husband smoked (11.51 vs 17.98 ng/mg) and was unrelated to various indices of
      smoking by the husband. Japanese epidemiological studies using "marriage to a
      smoker" to index ETS exposure may therefore have compared groups with similar ETS
      exposure, suggesting that associations reported between lung cancer and this
      index in some of these studies may result from bias. While other biases,
      including confounding, may also be important, bias resulting from smoking
      misclassification combined with husband/wife smoking concordance is shown to be
      of major concern. The high misclassification rates in Japan, much higher than in
      Western populations, undermine conclusions from epidemiological studies conducted
      there.

PMID- 8543376
TI  - Estimation of mercury dose by a novel quantitation of elemental and inorganic
      species released from amalgam.
AB  - Amalgam fillings constitute, after food, the main source of exposure to mercury
      for the general population. An evaluation of potential health risks has to be
      based on the dose of mercury released from the fillings. This dose is estimated
      by a new procedure of mercury speciation which elutes the released elemental and
      inorganic mercury with solvents of different polarity (paraffin and saline). In
      vitro tests with spherical amalgam pellets have shown that mercury release into
      the solvents is linearily correlated to time and amalgam surface area. Doses
      estimated in volunteers by this method average 4.5 micrograms/day (range 0.3
      13.9), as compared to a dose of 3.4 micrograms/day (range 0.1-11.8) measured
      conventionally in the oral air. The aforementioned dose, combined with the nearly
      equal mercury uptake from food, is below the acceptable daily intake of 40
      micrograms for all forms of mercury.

PMID- 8543377
TI  - Evaluation of noise-induced hearing loss by reference to the upper limit of
      hearing.
AB  - We have defined the upper limit of hearing as the maximum audible frequency
      measured with fixed intensity and changing frequency. We have previously
      established the standard upper limit ageing curves from the normal age variation
      in the upper limit of hearing. In the present study, we sought to clarify the
      effects of occupational noise on the upper limit of hearing. We measured the
      upper limit of hearing in 239 healthy male workers (478 ears) exposed to
      intensive occupational noise. Their age variation in the upper limit of hearing
      was compared with the standard upper limit ageing curves in males. There were
      statistically significant deteriorations. Even if the ears that had normal
      hearing levels (35 dB or less) were selected, deterioration in the upper limit of
      hearing was noticeable. The upper limit of hearing may serve as clinically useful
      information on the hearing impairment that precedes noticeable hearing impairment
      in conventional audiometry for workers exposed to intensive occupational noise.

PMID- 8543378
TI  - Reproducibility of basal and induced DNA single-strand breaks detected by the
      single-cell gel electrophoresis assay in human peripheral mononuclear leukocytes.
AB  - The aim of the reported study was to investigate the reproducibility of the
      single-cell gel electrophoresis (SCGE) assay in the determination of DNA single
      strand breaks (SSBs) and to estimate the statistical requirements when the SCGE
      assay is used for the detection of genotoxicity in humans. In human peripheral
      mononuclear leukocytes (PMLs), we repeatedly measured the rate of SSBs after in
      vitro incubation of cells for 1 h at 4 degrees C in phosphate buffered saline
      (PBS, basal) or 10 microM or 50 microM H2O2 (induced). Intra-assay variation was
      determined from cryopreserved PMLs of a single donor. To assess intrasubject and
      intersubject variation, PMLs of ten healthy, nonsmoking subjects (aged 19-37
      years) were tested 5-9 times. Cryopreserved cells revealed a mean coefficient of
      variation of 18% (PBS) and 7%-9% (H2O2). There were statistically significant
      differences between individuals in the rate of SSBs after incubation in PBS (P <
      0.01), 10 microM H2O2 (P < 0.001), and 50 microM H2O2 (P < 0.001). The range of
      interindividual variability was 26% for basal and 12%-13% for induced SSBs, and
      the coefficient of intraindividual variation was 18%-72% (PBS) and 7%-23% (H2O2).
      Neither basal nor induced rates of DNA damage were related to gender or age.
      Estimates of the minimum detectable effects were based on these observed sources
      of variability (power 90%, level of significance 5%, assumed sample size 50).
      With two different groups, a difference of 31% in basal SSBs or 12% in induced
      SSBs would be detectable. Repeated measurement within one group could detect a
      difference of 26% in basal and 9% in induced SSBs. In summary, the SCGE assay
      appears to be suitable for the detection of single-strand breaks, e.g., in
      biomonitoring or environmental medicine, and the statistical requirements could
      be derived from our analysis of the sources of variability.

PMID- 8543379
TI  - Chronic and acute respiratory effects among grain mill workers.
AB  - Exposure to flour dust may induce chronic respiratory manifestations as well as
      acute ventilatory effects. We compared the prevalence of respiratory symptoms,
      ventilatory impairment, and variations in pulmonary function over the workshift
      in a group of mill workers exposed to wheat flour and in referent workers. One
      hundred and forty-two men exposed to flour in a mill and 37 referent workers were
      included in this study. Each subject completed a standardized questionnaire.
      Pulmonary function tests were performed before and after the workshift. The
      assessment of environmental exposure to flour showed high concentrations during
      some jobs with a high percentage of inhalable particles and a low concentration
      of respirable particles. The exposed workers had a significantly higher
      prevalence of usual cough and usual phlegm than the referents. The prevalence of
      asthma, based on the questionnaire, was similar. Before the workshift, the
      exposed workers had significantly lower mean lung function values for peak flow
      rate and forced expiratory flow rate at 75% of the vital capacity than the
      referents. After the workshift, all the lung function values showed a slight
      decrease, significant for forced vital capacity and forced expiratory volume
      during 1 s in both groups. Among the exposed workers, the asthmatic subjects had
      a significantly higher decrease across the shift than the nonasthmatic workers.
      This result is probably linked to bronchial hyperreactivity. Among nonasthmatic
      subjects, the decrease was larger in nonexposed workers than in exposed workers.
      A higher prevalence of respiratory symptoms and lower pulmonary function values
      were observed among mill workers by comparison with referents. Moreover, the data
      suggest that asthmatic status and the time of spirometric measurements need to be
      taken into account in epidemiological studies on exposure to airborne allergens.
      In addition, the study does not exclude a healthy worker effect with selection of
      dust-resistant subjects or better identification of asthmatic subjects among the
      workers exposed to an allergenic substance than among the nonexposed workers.

PMID- 8543380
TI  - Cancer risk assessment for health care workers occupationally exposed to
      cyclophosphamide.
AB  - In the present study a cancer risk assessment of occupational exposure to
      cyclophosphamide (CP), a genotoxic carcinogenic antineoplastic agent, was carried
      out following two approaches based on (1) data from an animal study and (2) data
      on primary and secondary tumors in CP-treated patients. Data on the urinary
      excretion of CP in health care workers were used to estimate the uptake of CP,
      which ranged from 3.6 to 18 micrograms/day. Based on data from an animal study,
      cancer risks were calculated for a health care worker with a body weight of 70 kg
      and a working period of 40 years, 200 days a year (linear extrapolation). The
      life-time risks (70 years) of urinary bladder cancer in men and leukemias in men
      and women were found to be nearly the same and ranged from 95 to 600 per million.
      Based on the patient studies, cancer risks were calculated by multiplication of
      the 10-year cumulative incidence per gram of CP in patients by the estimated mean
      total uptake in health care workers over 10 years, 200 days a year. The risk of
      leukemias in women over 10 years ranged from 17 to 100 per million using the
      secondary tumor data (linear extrapolation). Comparable results were obtained for
      the risk of urinary bladder tumors and leukemias in men and women when primary
      tumor data were used. Thus, on an annual basis, cancer risks obtained from both
      the animal and the patient study were nearly the same and ranged from about 1.4
      to 10 per million. In The Netherlands it is proposed that, for workers, a cancer
      risk per compound of one extra cancer case per million a year should be striven
      for ("target risk") and that no risk higher than 100 per million a year
      ("prohibitory risk") should be tolerated. From the animal and the patient study
      it appears that the target risk is exceeded but that the risk is still below the
      prohibitory risk.

PMID- 8543381
TI  - The Atlas of Health and Working Conditions by Occupation. 1. Occupational ranking
      lists and occupational profiles from periodical occupational health survey data.
AB  - In this article, we describe methods which have been applied in the compilation
      of the Atlas of Health and Working conditions by Occupation. First, we discuss
      the need for information systems to identify problems concerning working
      conditions and health. Such information systems have an exploratory purpose,
      being deployed to identify work risks in companies, groups of occupations and
      sectors of industry, and can also be a starting point for the generation of
      hypotheses on the causes of adverse health effects. In the Netherlands,
      occupational health services gather questionnaire data about work and health as
      part of periodical occupational health surveys. In the atlas, aggregated
      questionnaire data for 129 occupations with male employees and 19 occupations
      with female employees are presented. In this article, we explain the methodology
      used to compare occupations with regard to each item in the questionnaire. We
      then discuss applications of these occupational ranking lists. The cross
      sectional nature of the data collection, various forms of selection and the
      limited size of some occupational populations have to be taken into account when
      interpreting the results. Occupational ranking lists can be applied in the
      allocation of resources and in the design of scientific research. The overviews
      for each occupation, presented in the second half of the atlas, provide an
      occupational profile of existing problems with respect to work and health. These
      profiles are used as basic information to develop a practical policy on working
      conditions and health.

PMID- 8543382
TI  - The Atlas of Health and Working Conditions by Occupation. 2. A comparison with
      the "Atlas of Health and Working Conditions in the Construction Industry".
AB  - The results of the general Atlas of Health and Working Conditions by Occupation
      were compared with the results of the Atlas of Health and Working Conditions in
      the Construction Industry. Both are based on questionnaire data from periodical
      occupational health surveys [POHSs]. The scores on most of the items showed
      considerable differences between the two atlases, partly due to differences in
      the regional origin of the data. Therefore, direct comparisons between the
      atlases are biased by regional differences. To study the reliability and the
      generalizability of the results of both atlases, similarities between the data
      files with respect to occupations in the construction industry were studied. Most
      of the items on working conditions, especially those with a widespread
      distribution, showed a close resemblance between the data files in terms of the
      relative position of an occupation compared to other occupations in the
      construction industry. The items on health showed less resemblance, except for
      the items on musculoskeletal complaints, which showed results similar to those of
      the work items. These results indicate the reliability and generalizability of
      the judgements based on both atlases outside the regions of origin, as far as
      items with a widespread distribution are concerned. Therefore, we recommend the
      aggregation of POHS data on a national scale, taking regional differences into
      account. In that way, a greater number of occupations will be described and the
      reliability of the results will be enhanced.

PMID- 8543383
TI  - Occurrence of pleural plaques in workers with exposure to mineral wool.
AB  - The objective of this study was to investigate whether occurrence of pleural
      plaques is associated with exposure to mineral wool. The occurrence of pleural
      plaques on routine chest radiographs of 933 persons employed in the mineral wool
      manufacturing industry and 865 referents was compared. Twelve men from the
      mineral wool industry had pleural plaques, as against three of the referents (P >
      0.05). The occurrence of pleural plaques among men in the mineral wool industry
      was not associated with an increased exposure to mineral wool or with length of
      time between start of employment and time of chest radiograph. The results do not
      support the notion that inhalation of man-made mineral fibers causes pleural
      plaques. It must, however, be conceded--keeping in mind the limits imposed by the
      study size--that nor do they provide grounds for refutation of such a hypothesis.

PMID- 8543384
TI  - Estimation of the degree of acclimatization to high altitude by a rapid and
      simple physiological examination.
AB  - The recent expansion in the geographical areas open to human activity has made it
      desirable to have an objective method to evaluate the degree of high-altitude
      acclimatization. In this study, we measured the arterial oxygen saturation value
      at rest and just after exercise in healthy high-altitude trekkers using a
      transportable pulse oximeter. During a 100-day stay at high altitude (around 4000
      m), the degree of arterial hemoglobin saturation measured at rest was relatively
      stable. However, shortly after arrival at high altitude, even light exercise
      induced an acute reduction in the degree of arterial hemoglobin saturation; this
      reduction was ameliorated as the trekkers became acclimatized to the high
      altitude. Preliminary short trekking to high altitudes does not appear sufficient
      to induce this response. It is suggested that this rapid and simple physiological
      examination, the measurement of arterial oxygen saturation value after light
      exercise, could be a convenient means of estimating the level of high-altitude
      acclimatization among healthy subjects.

PMID- 8543385
TI  - Correlation of DNA ploidy and S-phase fraction with chemotherapeutic response and
      survival in a randomized study of disseminated malignant melanoma.
AB  - DNA ploidy and S-phase fraction were measured by flow cytometry in the tumour
      tissue of 87 patients with disseminated malignant melanoma, who had been
      classified either as responders or with progressive disease in a study of the
      effects of 2 chemotherapeutic regimens. The patients had been randomized to
      receive treatment with dacarbazine (DTIC) and vindesine (Eldesine) with or
      without addition of cisplatin (Platinol). Tumour tissue was obtained from both
      the primary tumours and the last histologically verified metastases, but in some
      cases only the primary tumours or the last metastases could be evaluated. There
      was a significantly higher mean S-phase value in melanoma metastases from
      patients with complete or partial responses compared with patients with
      progressive disease. Neither the S-phase fraction of the primary tumour, nor the
      DNA ploidy of the primary tumour or of the last histologically verified
      metastases taken before inclusion into the study were associated with therapeutic
      response. In the multivariate analysis, both the anatomical location of the
      metastases and the S-phase fraction measured on the last metastases remained
      significant prognostic factors of response. In the univariate survival analysis,
      there was an association between high S-phase fractions of the metastases and
      longer survival. In the multivariate survival analysis, the S-phase fraction, the
      number of involved metastatic sites and the treatment response were independent
      predictive factors. We conclude that, in disseminated melanoma treated with
      chemotherapy, a high S-phase fraction measured in the last histologically
      verified metastases is associated with a higher response rate and a longer
      survival. Our results clearly support the role of S-phase measurement as a
      potential tool for selecting patients for treatment.

PMID- 8543386
TI  - Effect on tumorigenicity and metastasis of transfection of a diploid benign rat
      mammary epithelial cell line with DNA corresponding to the mRNA for basic
      fibroblast growth factor.
AB  - To examine the potential role of fibroblast growth factors (FGF) in tumorigenesis
      and metastasis, plasmid constructs containing the human basic FGF (bFGF) gene,
      with or without fusion to a secretory signal peptide (IgbFGF), were transfected
      into the diploid rat mammary epithelial cell line Rama 37. All transfectants
      possessed multiple copies of the transfected cDNA, which was expressed as the
      corresponding mRNA and the protein. The amount of bFGF protein was usually
      greater than the bFGF growth-stimulatory activity that could be recovered from
      the transfected cells. Nevertheless, the amount of bFGF growth-stimulatory
      activity secreted by the IgbFGF transfectants (0.08-0.8 ng/ml/24 hr) was
      sufficient to induce growth in responsive cells. However, the transfectants
      themselves were refractory to stimulation by exogenously added bFGF, despite
      possessing a small number of high-affinity receptors for bFGF. When the bFGF or
      the IgbFGF transfectants were inoculated into the mammary fat pads of syngeneic
      rats, the tumour incidence was low (0-50%). However, when cells cultured from
      these tumours were inoculated into the fat pad of syngeneic rats, the tumour
      incidence was 100%. Tumours were in all cases benign and no metastases were
      observed. Our results suggest that the role of bFGF in metastasis is not simply
      one of autocrine/paracrine stimulation of cell growth and that other events may
      also be required.

PMID- 8543387
TI  - Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient,
      macrophage-deficient op/op mouse: evidence for a role of CSF-1-dependent
      macrophages in formation of tumor stroma.
AB  - Macrophages have been suggested to play a major role in the immune response to
      cancer. They have also been suggested to stimulate the formation of tumor stroma
      and to promote tumor vascularization. The availability of the op/op mouse, which
      has no endogenous colony-stimulating factor 1 (CSF-1) and which possesses a
      profound macrophage deficiency, provides a new model to verify these notions.
      Subcutaneous growth of transplantable Lewis lung cancer (LLC) is markedly
      impaired in the op/op mice compared with normal littermates. Treatment of tumor
      bearing op/op mice with human recombinant CSF-1 corrects this impairment.
      Histological analysis of tumors grown in op/op and normal mice revealed marked
      differences. Tumors grown in op/op mice display a decreased mitotic index and
      pronounced necrosis, particularly hemorrhagic. Moreover, particularly in the
      op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood)
      have been observed. These tumors, in contrast to tumors grown in normal mice, are
      almost deprived of regular arteries and veins. In contrast to tumors grown in
      normal mice, they exhibit almost no Sirius red-stained collagenous fibers and
      Gomori silver-stained reticular fibers. Our data suggest that the CSF-1-dependent
      macrophage subpopulation missing in op/op mice plays a primary role in supporting
      tumor stroma formation and tumor vascularization in murine LLC tumors.

PMID- 8543388
TI  - Differential regulation of breast tumor cell proliferation by stromal fibroblasts
      of various breast tissue sources.
AB  - A stromal fibroblast-mediated paracrine regulation of epithelial tumor cell
      proliferation and differentiation plays an important role in the development and
      progression of breast tumors. We have studied the paracrine growth regulation of
      various phenotypically different breast cancer cell lines using conditioned serum
      free media (C-SFM) from primary breast fibroblasts. Fibroblast cultures were
      established from malignant primary tumors and adjacent normal breast tissue,
      benign fibroadenomas, cosmetic reduction mammoplasties and breast skin tissues.
      All fibroblast-conditioned media were shown to stimulate the proliferation of
      breast cancer cell lines. However, the C-SFM-induced MCF-7 proliferative response
      was shown to be significantly higher than the proliferative response observed
      with any of the other cell lines tested. More importantly, the MCF-7
      proliferative response obtained with malignant tumor tissue fibroblast C-SFM was
      shown to be significantly higher than the response to C-SFM from paired (and
      unpaired) normal adjacent breast tissue fibroblasts. The MCF-7 proliferative
      response to fibroblast C-SFM from normal tissue (adjacent to the tumor) was
      further shown to be comparable to the MCF-7 response using benign or reduction
      mammoplastic tissue fibroblast C-SFM. In addition, we show that IGFs are only
      partly responsible for the observed proliferative effect of the C-SFMs, while
      EGF, TGF alpha and basic-FGF are shown not to be involved. We conclude that
      stromal fibroblasts can differentially regulate breast cancer cell proliferation.
      Both the fibroblast's tissue source as well as the target tumor cell's phenotype
      will determine the extent of the proliferative response.

PMID- 8543389
TI  - Iodine supplementation in Sweden and regional trends in thyroid cancer incidence
      by histopathologic type.
AB  - We studied regional patterns of thyroid cancer incidence in relation to iodine
      intake and iodinization in Sweden using 5,838 incident cases diagnosed in the
      period 1958-1981. Region was defined either by iodine status, urban-rural status
      or health-care region (internal controls). Age, period and cohort models were
      fitted to evaluate trends and regional variation in incidence by histopathologic
      type. In iodine-deficient areas, the relative risk (RR) of developing thyroid
      cancer was 0.92 for all histologic types combined, 0.80 for papillary cancer and
      0.87 for anaplastic carcinoma. Residence in iodine-deficient regions was
      associated with a 2-fold increased risk of follicular cancer in men (RR 1.98) and
      a 17% increase in risk in women (RR 1.17). Regional differences in iodine intake
      fell after iodinization of the food supply, which was started in 1936 and
      enhanced in 1966. Nevertheless, incidence of both papillary and follicular
      carcinoma increased during the study period, with largely similar trends in
      iodine-deficient and iodine-sufficient areas. Overall, residence in urban or
      rural areas was not an important determinant of incidence, though trends in the
      incidence of papillary, follicular and anaplastic cancer did vary between urban
      and rural areas. The occurrence of thyroid cancer differed only marginally
      between the 6 health-care regions in Sweden, suggesting that the observations in
      regions defined by iodine intake were unlikely to be artifactual. Our data
      suggest that iodinization of the food supply is not associated with adverse
      trends in the occurrence of thyroid cancer.

PMID- 8543390
TI  - Preferred nucleotide sequence at the integration target site of human T-cell
      leukemia virus type I from patients with adult T-cell leukemia.
AB  - Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with
      adult T-cell leukemia/lymphoma (ATL). We cloned and sequenced host DNA adjacent
      to the long terminal repeats of HTLV-I from uncultured leukemic cells of 4 ATL
      patients. The region flanking the provirus was generally A/T-rich (60-64% A/T),
      and a nucleotide composition bias was noticed when sequences within 25 bp on both
      sides of the integration target site were analyzed. In the 6-bp direct repeat,
      both end positions are preferentially occupied by G/C, whereas the middle
      positions are preferentially occupied by A/T. Furthermore, AA or TT dinucleotides
      are frequently present on each side adjacent to the center of the direct repeat.
      Our finding suggests preferential integration target sites of HTLV-I in the host
      genome. Further study is warranted to determine whether each of the target
      sequence preference is a general property of HTLV-I integration or may be
      associated with the leukemogenesis of ATL.

PMID- 8543391
TI  - Herpesvirus-like DNA sequences detected in endemic, classic, iatrogenic and
      epidemic Kaposi's sarcoma (KS) biopsies.
AB  - The identification of Kaposi's sarcoma (KS) clusters in sub-equatorial Africa
      (endemic KS, AKS) and the high frequency of KS in sexually transmitted AIDS
      (epidemic KS, EKS), have previously suggested a role for infectious agents in the
      etiopathogenesis of KS. The recent identification of herpesvirus (HHV)-like DNA
      sequences in one case of EKS and their detection in > 90% of all tested EKS,
      prompted us to determine the prevalence of these viral sequences in all types of
      KS, such as AKS, EKS, classic KS (CKS) and iatrogenic KS (IKS). The presence of
      herpesvirus(HHV)-like DNA sequences has been examined in 61 KS skin tumors
      obtained from Greece, Italy, USA, Uganda and Kenya. All KS types (100%) were
      positive by polymerase chain reaction (PCR) and Southern-blot analysis, while 5
      out of 6 (83%) and 4 out of 7 (57%) uninvolved autologous skin biopsies from AKS
      and CKS patients, respectively, were positive for HHV-like sequences. All samples
      from non-KS patients were negative, i.e. 17 human biopsies from healthy
      individuals or patients affected by other pathologies, 5 human cell lines and 15
      peripheral blood mononuclear cells (PBMC) from HIV-positive subjects. These
      results suggest that HHV-like sequences play a major role in the pathogenesis of
      this neoplasm.

PMID- 8543392
TI  - Histopathological characteristics of childhood thyroid cancer in Gomel, Belarus.
AB  - We reviewed histopathologically 19 cases of childhood thyroid cancer occurring
      between 1991 and 1994 among 14,396 screening subjects in Gomel, Republic of
      Belarus, the region most severely radio-contaminated by the Chernobyl nuclear
      power plant accident in 1986. The patients were 13 girls and 6 boys with a mean
      age of 10.6 years. The mean age at the time of the accident was 3.2 years. Mean
      tumor diameter was 16 mm, and all cases were papillary carcinoma with various
      amounts of solid component. Psammoma bodies and stromal fibrosis were encountered
      to some extent in almost all cases. The tumors were highly prone to local
      invasion and regional lymph-node metastasis. No morphological evidence for
      radiation-induced cancer was obtained in these cases. 137Cs levels were
      relatively high in the patients' bodies and in the soil at the places of
      domicile. However, there was no dose-response relationship between cancer
      prevalence and radioactivity. These facts suggest that the incidence of
      aggressive pediatric thyroid cancer is extremely high in Gomel, where most of the
      children were exposed to a low level of radioactivity over a long time after the
      accident. At present, however, no definite conclusion can be drawn on the
      relationship between cancer occurrence and radioactive contamination.

PMID- 8543393
TI  - Childhood cancer incidence in Australia, 1982-1991.
AB  - The data of the Australian Paediatric Cancer Registry on childhood cancer
      incidence in Australia for the 10-year period 1982-1991 are presented. The crude
      average annual incidence of cancer in children under the age of 15 years was 13.8
      per 100,000. The incidence of childhood cancer in Australia is rising.
      Significant increases were seen in acute non-lymphoblastic leukaemia, astrocytoma
      and melanoma. The age-standardised incidence of 14.4 per 100,000 is about 34%
      higher than in the UK. Most types of cancer had a higher incidence in Australia
      than in the UK, and the difference was significant for acute lymphoblastic
      leukaemia, astrocytoma and melanoma. Of particular interest is malignant
      melanoma, whose incidence in Australia is more than 5 times that in the UK, as a
      result of excessive UV exposure. Australia has a higher incidence of Ewing's
      tumour than osteosarcoma, nearly twice that of the UK. International comparative
      studies may help to elucidate the aetiology of these tumours.

PMID- 8543394
TI  - Cancer in offspring of parents engaged in agricultural activities in Norway:
      incidence and risk factors in the farm environment.
AB  - In this study of cancer in offspring we demonstrate that factors linked to
      horticulture and use of pesticides are associated with cancer at an early age,
      whereas factors in animal husbandry, in particular poultry farming, are
      associated with cancers in later childhood and young adulthood. Incident cancer
      was investigated in offspring born in 1952-1991 to parents identified as farm
      holders in agricultural censuses in Norway in 1969-1989. In the follow-up of
      323,292 offspring for 5.7 million person-years, 1,275 incident cancers were
      identified in the Cancer Registry for 1965-1991. The standardized incidence for
      all cancers was equal to the total rural population of Norway, but cohort
      subjects had an excess incidence of nervous-system tumours and testicular cancers
      in certain regions and strata of time that could imply that specific risk factors
      were of importance. Classification of exposure indicators was based on
      information given at the agricultural censuses. Risk factors were found for brain
      tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig
      farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI),
      1.89-5.13]; indicators of pesticide use had an independent effect of the same
      magnitude in a dose-response fashion, strongest in children aged 0 to 14 years
      (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were
      associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's
      lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some
      common cancers of adolescence, and was strongest for osteosarcoma and mixed
      cellular type of Hodgkin's disease. The main problem in this large cohort study
      is the crude exposure indicators available; the resulting misclassification is
      likely to bias any true association towards unity.

PMID- 8543395
TI  - Differential immunohistochemical detection of transforming growth factor alpha,
      amphiregulin and CRIPTO in human normal and malignant breast tissues.
AB  - The expression of growth factors, such as transforming growth factor alpha (TGF
      alpha), amphiregulin (AR) and CRIPTO, a type-1 tyrosine-kinase growth factor
      receptor (erbB-2), and a tumor-suppressor gene (p53), that have been implicated
      in the development and/or the progression of breast cancer, was evaluated by
      immunohistochemistry in 100 human primary infiltrating breast carcinomas (IBC).
      AR and CRIPTO immunoreactivity was also assessed in 55 human breast ductal
      carcinomas in situ (DCIS). Within the 100 IBC, 80, 50, 73, 17, and 34 tumors
      expressed moderate to high levels of TGF alpha, AR, CRIPTO, erbB-2, and p53
      respectively. In addition, AR and CRIPTO immunoreactivity were found in 11 and in
      26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal
      mammary-gland samples were weakly positive for TGF alpha, AR, and CRIPTO
      expression, respectively, whereas none was positive for erbB-2 or p53. Within the
      100 IBC, expression of erbB-2 significantly correlated with high histologic and
      nuclear grading, with high growth fraction, and with estrogen-receptor (ER)- and
      progesterone-receptor (PgR)-negative tumors. A statistically significant
      correlation was also observed between p53 expression and high histologic grading,
      high growth fraction, and PgR-negative tumors. In contrast, no significant
      correlations were found between TGF alpha, AR, and CRIPTO immunoreactivity and
      various clinicopathological parameters, with the exception of a positive
      correlation between TGF alpha and ER expression. These data demonstrate that TGF
      alpha, AR, and CRIPTO expression are significantly increased in malignant mammary
      epithelium relative to normal epithelium. In particular, the differential
      expression of CRIPTO may serve as a potential tumor marker for breast
      carcinogenesis.

PMID- 8543396
TI  - 92 kDa type IV collagenase (MMP-9) is expressed in neutrophils and macrophages
      but not in malignant epithelial cells in human colon cancer.
AB  - Degradation of the extracellular matrix during cancer invasion is accomplished by
      the concerted action of several proteolytic enzymes, including matrix
      metalloproteinases (MMPs). We have studied the immunohistochemical localization
      of one of these enzymes, 92-kDa type IV collagenase (MMP-9), in short-term fixed
      specimens of 19 colon adenocarcinomas and 2 biopsies of adjacent normal colon.
      Staining was confined to neutrophils and macrophages, as identified by double
      staining. All neutrophils were positive in all cases. Some positively stained
      tumor-infiltrating macrophages were seen in 6 (32%) of the tumors, located
      adjacent to invasive tumor glands. No cancer cells were stained in any of the
      cases. In normal colon tissue, staining was only seen of scattered neutrophils in
      vessels and of macrophages in Peyer's patches. Routinely processed specimens from
      7 of the 19 carcinomas were analyzed by in situ hybridization. In agreement with
      previous results, a MMP-9 mRNA signal was in all cases seen in a subpopulation of
      tissue macrophages surrounding invasive tumor glands, while no MMP-9 mRNA was
      detected in any other cell types, including neutrophils and cancer cells. Our
      results indicate that in this type of cancer all neutrophils contain MMP-9, which
      has been produced before they infiltrate the tumors; that a subpopulation of the
      tumor-infiltrating macrophages most likely in all cases produces MMP-9 but that
      the content of this protein is low due to a rapid turnover and that malignant
      epithelial cells do not produce or contain detectable amounts of MMP-9. These
      findings extend previous results indicating that stromal cells are actively
      involved in the generation and regulation of extracellular proteolysis during
      cancer invasion.

PMID- 8543397
TI  - Promoter usage in the E7 ORF of HPV16 correlates with epithelial differentiation
      and is largely confined to low-grade genital neoplasia.
AB  - Human papillomavirus type 16 (HPV16) transcription in HPV16-positive vulvar
      intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN) and
      cervical carcinomas was analyzed using RNA-RNA in situ hybridization. Subgenomic
      probes were constructed which specifically detected individual spliced E6/E7
      transcripts as well as transcripts initiated within the E7 open reading frame
      (ORF). In most biopsies, viral RNA was predominantly initiated in the E6 ORF at
      promoter P97 and contained the E6*I splice. Three of 7 VIN, 13 of 37 CIN and I of
      13 cervical carcinomas expressed significant amounts of mRNA that were initiated
      within the E7 ORF. Promoter activity in the E7 ORF correlated with epithelial
      differentiation and viral late gene (LI) expression. Our data therefore do not
      support the finding of Bohm et al. (1993) which suggested that the predominant
      transcript(s) in HPV16-associated high-grade neoplasms and genital carcinomas is
      initiated within the E7 ORF. Rather, our data suggest that the major HPV16
      transcript in high-grade cervical neoplasms and carcinomas is initiated in the E6
      ORF and encodes the E7 oncoprotein.

PMID- 8543398
TI  - Response to epirubicin in patients with superficial bladder cancer and expression
      of the topoisomerase II alpha and beta genes.
AB  - Biopsies of superficial bladder cancer were analysed to study the relationship
      between response to epirubicin and the expression of the human topoisomerase II
      alpha and beta genes. Tissue samples were obtained prior to treatment and a
      marker tumour was left in the bladder. Transcript levels of both genes were
      generally lower in biopsies taken following treatment failure. Levels of
      topoisomerase II mRNA were uniformly lower in tumour tissue than in biopsies of
      normal tissue.

PMID- 8543399
TI  - International renal cell cancer study. VII. Role of diet.
AB  - We investigated the role of diet in the etiology of renal cell cancer (RCC) in a
      multi-center, population-based case-control study conducted in Australia,
      Denmark, Sweden and the United States, using a shared protocol. A total of 1,185
      incident histopathologically confirmed cases (698 men, 487 women) and 1,526
      controls (915 men, 611 women) frequency-matched to cases by sex and age were
      included in the analyses. The association between RCC and diet was estimated by
      relative risks (RR) and 95% confidence intervals (CI) adjusted for age, sex,
      study center, body mass index and smoking. A statistically significant positive
      association was observed for total energy intake (RR = 1.7, 95% CI = 1.4-2.2 for
      the highest vs. lowest quartile, p value for trend < 0.00001), while the
      hypothesis that protein and fat are risk factors independent of energy was not
      supported. Fried meats were associated with increased RCC risk, while vegetables
      and fruits were protective, with the strongest effect observed for the highest
      quartile of consumption of orange/dark green vegetables but not vitamin C or beta
      carotene. Increased risk was associated with low intake (lowest decile) of
      vitamin E and magnesium. We observed an apparent protective effect of alcohol
      confined to women and probably due to chance. Our findings indicate an important
      role of nutrition in the development of RCC. The apparent positive association of
      energy intake with risk of RCC needs further investigation in a prospective
      cohort study to exclude the possible impact of differences in recall between
      cases and controls.

PMID- 8543400
TI  - Reversal of multi-drug resistance in vitro by fatty acid-PEG-fatty acid diesters.
AB  - Fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS 15, that modulate
      multi-drug resistance (MDR) have been described; however, the drug potential of
      these preparations is unclear because of the molecular heterogeneity of these and
      other commercial surfactants. In previous experiments, an active but still
      polydisperse preparation, designated CRL 1337, was synthesized by reacting
      purified oleic acid with a 20-fold molar excess of ethylene oxide. We have
      subjected this preparation to chromatographic separation, and infrared analysis
      of the active fractions revealed a significant component of diester structures
      (fatty acid-PEG-fatty acid). A new generation of diester compounds has now been
      synthesized. Preparations comprised of 99% diesters were significantly more
      potent than monoester preparations for MDR modification activity in vitro. As
      previously determined for ethylene oxide-derived preparations similar to CRL
      1337, the nature of the fatty acid domains proved to be important for activity,
      as was the relative length of the polyethylene glycol domain (which determines
      the hydrophile-lipophile balance). The ester linkage appeared unimportant since
      homologous diethers and diamides had activity similar to that of diesters.
      Stearic acid diester was 1.5- to 7-fold more potent than CRL 1337 when tested in
      cell proliferation inhibition assays. In light of these structural restrictions
      on drug potentiation, and since these surfactants are active at relatively low
      concentrations (below 1 microgram/ml), investigations of their mechanism of
      action were initiated by exploring specific interactions with P-glycoprotein.
      Both active and inactive diesters inhibited azidopine labeling of P-glycoprotein,
      suggesting that fatty acid-PEG diesters can interfere with P-glycoprotein
      substrate binding. Other attributes of these preparations must contribute to
      their ability to reverse MDR.

PMID- 8543401
TI  - In vivo studies with interleukin-12 alone and in combination with monocyte colony
      stimulating factor and/or fractionated radiation treatment.
AB  - Interleukin-12 (IL-12) was found to be an active anti-tumor agent in 3
      established murine solid tumors: B16 melanoma, Lewis lung carcinoma and renal
      cell carcinoma (RenCa). IL-12 was well tolerated over a 100-fold dose range. Only
      the high-dose treatment of IL-12 resulted in a clear reduction in the number of
      lung metastases from B16 melanoma and Lewis lung carcinoma. Treatment of animals
      bearing Lewis lung carcinoma with IL-12 in combination with fractionated
      radiation therapy was markedly dose-modifying, indicating that IL-12 was acting
      synergistically with radiation. Treatment of animals bearing the same tumor with
      monocyte colony-stimulating factor (M-CSF) along with fractionated radiation
      therapy resulted in a parallel increase in tumor growth delay with increasing
      dose of M-CSF, indicating that M-CSF was affecting a subpopulation of tumor cells
      in addition to those killed by radiation therapy. The combination of IL-12 with M
      CSF was most effective with radiation therapy, especially in the clinically
      relevant dosages of 2 and 3 Gy per fraction. By isobologram analysis, IL-12 and M
      CSF, along with fractionated radiation therapy, resulted in a greater-than
      additive (synergistic) tumor response.

PMID- 8543402
TI  - Prostatic cell lineage markers: emergence of BCL2+ cells of human prostate cancer
      xenograft LuCaP 23 following castration.
AB  - A model of prostate cancer progression based on the expression pattern of
      informative genes in the human prostate cancer xenograft LuCaP 23.1 is presented.
      Apparently, there are at least 2 tumor cell populations of LuCaP 23.1,
      representing 2 different phenotypes. One is NSE (neuron-specific enolase)
      positive and the other NSE-negative. NSE-positive tumors were recovered after
      hormone-independent growth in castrated mice. These hormone-independent tumors
      also expressed BCL2, a gene product shown to inhibit apoptosis. With NSE, BCL2
      and PSA (prostate-specific antigen) as identifying markers, the model specifies a
      putative progression sequence of the prostate cancer cell types. We also show a
      proposed lineage relationship among the 3 principal normal cell types found in
      the prostatic epithelium.

PMID- 8543403
TI  - Long-term productive human cytomegalovirus infection of a human neuroblastoma
      cell line.
AB  - Human neuroblastoma cell line UKF-NB-4 persistently infected with human
      cytomegalovirus (HCMV) strain AD169 was established to study the effects of long
      term HCMV infection on virus production and phenotypic characteristics of tumour
      cells. The cells designated UKF-NB-4AD169 were subcultured (80 subcultures) over
      a period of more than 2 years after initiation of infection. UKF-NB-4AD169 cells
      continued to produce infectious virus in successive passages, with a titre
      ranging from 9 x 10(3) to 1 x 10(5) and from 2 x 10(1) to 2 x 10(2) plaque
      forming units per 10(6) cells and 1 ml culture medium, respectively; 10-20% of
      the cells produced HCMV-specific antigens, while 6-13% produced infectious virus
      progeny. The number of HCMV-specific DNA copies ranged from 9 x 10(4) to 9 x
      10(6) per 10(6) cells. Transmission electron microscopy confirmed the productive
      nature of HCMV infection. UKF-NB-4AD169 cultures proliferated, with population
      doubling time ranging from 24.5 to 26.6 hr (19.5 to 20.3 hr for UKF-NB-4) and
      cell viability from 79% to 85% (91-96% for UKF-NB-4). Significantly lower amounts
      of tyrosine hydroxylase and decreased activity for dopamine-beta-hydroxylase than
      in uninfected cells were observed in UKF-NB-4AD169 cells. However, the expression
      of N-myc oncoprotein was significantly increased in persistently infected
      cultures. Our results show that long-term productive HCMV infection of UKF-NB-4
      cell line is associated with the modulation of phenotypic properties, which may
      be related to the biological behaviour of neuroblastoma cells.

PMID- 8543405
TI  - Genetic and acquired cutaneous disorders associated with internal malignancy.

PMID- 8543404
TI  - The protective role of the immunomodulator AS101 against chemotherapy-induced
      alopecia studies on human and animal models.
AB  - The immunomodulator AS101 has been demonstrated to exhibit radioprotective and
      chemoprotective effects in mice. Following phase-I studies, preliminary results
      from phase-II clinical trials on non-small-cell-lung-cancer patients showed a
      reduction in the severity of alopecia in patients treated with AS101 in
      combination with chemotherapy. To further substantiate these findings, the
      present study was extended to include 58 patients treated either with the optimal
      dose of 3 mg/m2 AS101 combined with carboplatin and VP-16, or with chemotherapy
      alone. As compared with patients treated with chemotherapy alone, there was a
      significant decrease in the level of alopecia in patients receiving the combined
      therapy. The newly developed rat model was used to elucidate the protective
      mechanism involved in this effect. We show that significant prevention of
      chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined
      with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We
      show that this protection by AS101 is mediated by macrophage-derived factors
      induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1,
      since treatment of rats with IL-1 RA largely abrogated the protective effect of
      AS101. Moreover, we demonstrate that in humans there is an inverse correlation
      between the grade of alopecia and the increase in IL-1 alpha. In addition,
      protection by AS101 could be related to PGE2 secretion, since injection of
      indomethacin before treatment with AS101 and Ara-C partly abrogated the
      protective effect of AS101. To assess the ability of AS101 to protect against
      chemotherapy-induced alopecia, phase-II clinical trials have been initiated with
      cancer patients suffering from various malignancies.

PMID- 8543406
TI  - Oral candidosis.

PMID- 8543407
TI  - Cutaneous protothecosis.

PMID- 8543408
TI  - Nehushtan: teaching, training, and searching for the truth.

PMID- 8543409
TI  - Skin cancers at Tertiary Referral Skin Hospital in Singapore.
AB  - BACKGROUND: Skin cancer is the seventh most common cancer in Singapore. This
      study was performed to determine the pattern of skin cancers seen in a tertiary
      referral skin hospital. METHODS: Histologically confirmed skin cancers, seen
      between 1980 and 1991, were analyzed according to age, sex, race, site, and
      presence/absence of preexisting skin conditions. RESULTS: Of a total of 520
      patients, the commonest skin cancer was basal cell carcinoma (BCC) (36.5%),
      followed by squamous cell carcinoma (SCC) (24.4%), Bowen's disease (16.7%), and
      mycosis fungoides (9.0%). Malignant melanomas (2.7%) were rare. The sharp
      increase (26.2%) in BCC in the recent 3 years was largely contributed by a
      fivefold increase of non-resident Caucasian patients with BCC. All types of skin
      cancers were more common in Chinese (78.1%) and less frequent in the more
      pigmented races (9.4%). The men to women ratio was 1.72:1. The peak age
      distribution was in the 51-70-year group, with the exception of mycosis fungoides
      (31-50 years). The commonest site involved in BCC was the head and neck (67.0%)
      and in Bowen's disease the trunk (33.3%). Squamous cell carcinoma was found on
      the head and neck and the lower extremities with equal frequency (29.3%) and
      46.2% of all SCC on the lower extremities occurred in leprosy patients with
      chronic trophic ulcers. Of patients with Bowen's disease involving the
      nonsunexposed parts (trunk and upper extremities), 42.6% had probable arsenic
      exposure evident either from the history or clinical examination. Malignant
      melanomas were commonly located on the foot (71.4%). CONCLUSIONS: The commonest
      skin cancers seen were BCC, SCC, Bowen's disease, and mycosis fungoides. There
      were differences in the site distribution of SCC, Bowen's disease, and malignant
      melanomas in our study when compared to studies in Caucasians.

PMID- 8543410
TI  - Immunohistochemistry in histoid leprosy.
AB  - BACKGROUND: Histoid leprosy is a rare form of multibacillary leprosy as the
      result of secondary or even primary resistance to dapsone. The etiopathogenesis
      has not been clarified up to now. METHODS: An immunohistochemical study was
      carried out for the expression of various markers on epidermal and dermal cell
      populations using sections of frozen skin specimens from 5 patients with histoid
      leprosy as compared to specimens from 7 tuberculoid and 7 lepromatous patients.
      RESULTS: Dendritic epidermal cells, identified by monoclonal antibodies against
      CD1, HLA-DR, CD45, and CD36, were found reduced in histoid leprosy as compared to
      both tuberculoid and lepromatous groups. A gradual reduction of keratinocytic HLA
      DR expression from tuberculoid to lepromatous to histoid leprosy was observed.
      The pattern of CD36, CD4, and CD8 expression of lymphomonocytic cells in the
      dermis of histoid lesions was similar to that of tuberculoid leprosy, but without
      the formation of an organized granuloma. CD45+ cells as well as activated
      lymphocytic cells, expressed by the activation immunophenotype (CD1, HLA-DR,
      CD25, CD71, EGF-R) were found frequently in all groups. CONCLUSIONS: The in situ
      immunohistochemical findings support a modified hypersensitivity reaction of the
      cellular type that results in an inhibition of the lesional expansion, but not in
      the destruction of the bacilli within the histoid lesion.

PMID- 8543411
TI  - Mixed tumors with follicular differentiation: complex neoplasms of the primary
      epithelial germ.
AB  - BACKGROUND: Some mixed tumors of the apocrine variety also show characteristics
      of follicular and/or sebaceous differentiation. This can be explained because of
      the common embryologic origin of the three structures in the primary epithelial
      germ of the superficial ectoderm. METHODS: Twenty specimens of apocrine mixed
      tumors were studied by conventional microscopy. The specimens were evaluated
      searching for some features of folliculo-sebaceous differentiation. RESULTS:
      Certain features of folliculo-sebaceous differentiation were found in 45% of the
      samples examined. Additionally, different tumoral architectures were observed,
      resembling several well-characterized adnexal organoid neoplasms. In some tumors,
      there were also follicular structures of mesenchymal origin, similar to the
      dermal hair papilla and the arrector pili muscle. CONCLUSION: Apocrine mixed
      tumors of the skin illustrate the ability of pluripotential primordial cells to
      differentiate in different directions within an individual tumor. Moreover, mixed
      tumors appear as a compendium of different folliculo-sebaceous neoplasms. We
      suggest that these proliferations should be interpreted as "complex neoplasms of
      the primary epithelial germ."

PMID- 8543412
TI  - Idiopathic hypersensitivity vasculitis: clinicopathologic correlation of 61
      cases.
AB  - BACKGROUND: Little is known of the course and prognosis of hypersensitivity
      vasculitis (HV). METHODS: Sixty-one cases of idiopathic HV were biopsied and
      followed-up for 5 years. RESULTS: There were two predominant patterns of
      presentation: palpable purpura (PP) and vasculitic ulcers (VU). The former was
      self-limiting, whereas the prognosis of the latter was poor. Findings on
      histopathology correlate well in PP patients having acute episodes, whereas in
      patients with VU there is correlation with duration and recurrence. CONCLUSION: A
      biopsy of a fresh lesion is recommended to help in determining the outcome.

PMID- 8543413
TI  - KI-1 (CD30)-positive anaplastic large cell lymphoma mimicking an infectious
      granuloma.

PMID- 8543414
TI  - Pemphigus foliaceus coexisting with IgA nephropathy in a patient with psoriasis
      vulgaris.

PMID- 8543415
TI  - Dermatomyositis associated with diffuse dermal neutrophilia.

PMID- 8543416
TI  - Median nail dystrophy and habit tic deformity: are they different forms of the
      same disorder?

PMID- 8543417
TI  - Coma-induced epidermal necrolysis.

PMID- 8543418
TI  - Successful treatment of chromoblastomycosis due to Fonsecaea pedrosoi by the
      combination of itraconazole and cryotherapy.
AB  - BACKGROUND: Many methods and medications had been tried for the treatment of
      chromoblastomycosis with unsatisfactory results. Recently, there were several
      reports showing a good response of chromoblastomycosis to itraconazole, but it
      took as long as 18-30 months for lesions to heal. METHODS: Itraconazole, 200 to
      400 mg/day alone or in combination with monthly liquid nitrogen cryotherapy, was
      tried on 10 cases of chromoblastomycosis, caused by Fonsecaea pedrosoi in order
      to increase the potency of the drug and shorten the duration of treatment.
      RESULTS: The 10 cases included five newly diagnosed and five recalcitrant cases.
      Two patients were cured by 200 mg/day alone within 3 months. Seven patients
      required itraconazole, 400 mg/day, with combined cryotherapy to cure the lesions
      within 5 to 10 months. One case showed marked improvement but no cure. After the
      period of 1-year follow-up, only one case had a recurrent infection. CONCLUSIONS:
      Itraconazole was highly effective and may be useful in the treatment of
      chromoblastomycosis. A high dose is indicated in chronic fibrotic lesions in
      combination with liquid nitrogen cryotherapy, with higher efficacy and quicker
      healing than with medication alone.

PMID- 8543419
TI  - UV-protective sunglasses for UVA irradiation protection.
AB  - BACKGROUND: Eye protection with UVA-blocking solar shields is recommended on the
      day of PUVA treatment and the following day for our patients; however, many
      patients found this eyewear cosmetically unacceptable. METHOD: We investigated 34
      pairs of sunglasses to determine their suitability for providing adequate
      protection. The method used was modified from the technique used by Moseley et
      al. in 1988. RESULTS: We found that 21 (61.8%) of the 34 pairs of sunglasses and
      only 9 (53%) of the 17 pairs of sunglasses used by our patients were
      "satisfactory." Expensive brands and polarizing sunglasses do not guarantee
      optimal UVA protection. CONCLUSION: We recommend that all patients should use
      wrap-around solar shields for optimal eye-protection, while undergoing PUVA
      treatment. The availability of more cosmetically acceptable glasses will
      encourage better patients' compliance to protect their eyes with optical aids.

PMID- 8543420
TI  - Malignant hemangioendothelioma.
AB  - BACKGROUND: The administration of interleukin-2 (IL-2) has recently been reported
      to be favorable for treating malignant hemangioendothelioma (MHE). METHODS: Two
      patients with MHE responded well to intralesional injections of recombinant IL-2
      (rIL-2) without major side effects. The purpose of this study was to characterize
      cells infiltrating the regressing tumor following rIL-2 treatment.
      Immunohistochemical studies were performed on biopsy specimens taken from rIL-2
      injected lesional skin. RESULTS: It was shown that CD8+ lymphocytes and CD56+
      natural killer (NK) cells infiltrated at the rIL-2-injection sites, suggesting
      that these cells contributed to the tumor regression. In addition, MHE cells bore
      intercellular adhesion molecule-1 (ICAM-1) whose expression was augmented by rIL
      2 injections. CONCLUSIONS: These findings suggested, that rIL-2 not only induces
      lymphokine-activated killer (LAK) cells and NK cells, but also facilitates these
      cytotoxic cells to adhere to MHE cells by enhancing ICAM-1 expression of tumor
      cells.

PMID- 8543421
TI  - Dermatologic moulage in Japan.

PMID- 8543422
TI  - Malignant melanoma in Turner's syndrome.

PMID- 8543423
TI  - Chronic urticaria and hepatitis C.

PMID- 8543425
TI  - The conceptualisation and communication of clinical facts in psychoanalysis.

PMID- 8543424
TI  - Sarcoidosis presenting as cutaneous hypopigmentation.

PMID- 8543426
TI  - Seduction, persecution, revelation.
AB  - The author argues that seduction is not primarily a fantasy but a 'real'
      situation, which lies at the heart of the other two allegedly primal major
      scenarios: castration and the primal scene. This statement is not to be confused
      with an event-based realism, as, for this to be achieved, a third category of
      reality must be postulated. This reality, constantly misconstrued by authors as
      corresponding to material and psychological reality, is that of the message
      conveyed and, more specifically in the case of analysis, the enigmatic message.
      To establish his position the author re-examines Freud's presentation of the
      Schreber case. The sexual other and his intrusion are the essential points of
      Freud's analysis in the first part of his study. In the second part, however,
      desexualisation (in the name of love) and a return to the ego, as the centre of
      the whole process, both being evident in the 'primary' sentence from which Freud
      proposes to derive everything: 'I (a man) love him (a man)'. This leads us to a
      consideration of Fichte's concept of Bekanntmachung, the 'announcement' by the
      other and to an argument that the message stemming from the other is irreducible
      to a projection by the subject, within the three domains of primal seduction,
      paranoia and religious 'revelation'.

PMID- 8543427
TI  - Countertransference effects of absence.
AB  - In this paper the author aims to refine and explore some aspects of the clinical
      use and understanding of countertransference. Emphasising that
      countertransference is unconscious, the author proposes a specific approach
      focusing on the nature of the ongoing countertransference work that is required
      to unravel its meaning. Using a clinical vignette in which the analyst had to
      understand feeling impatient, irritated and then discouraged, the author
      describes how she was able eventually to understand what had been happening
      following insights she gained when she mistakenly understood how long a patient
      was going to be away and the function of the patient's response to her surprise
      on his return. This leads the author on to a wider consideration of the
      countertransferential work that may be needed when the analyst decides to take
      even regular breaks from patients, or when patients decide not to come. General
      aspects of the decisions analysts make about how and when to work as well as the
      specific opportunities presented when the occasion arises to inform patients of
      holiday arrangements, are considered. Finally, the author turns to possible
      countertransferential responses and the work that may be required when patients
      return to their sessions, whether they come back having suffered or acted out
      following the analyst's absence, or after having taken an absence of their own.

PMID- 8543428
TI  - Analysing forms of aliveness and deadness of the transference
      countertransference.
AB  - The sense of aliveness and deadness of the transference-countertransference
      represents a critical dimension of the analytic experience and may be the single
      most important measure of the moment-to-moment status of the analytic process. In
      this paper the author presents four clinical discussions that illustrate the
      importance of analysing the experience of aliveness and deadness in (of)
      transference-countertransference. In each vignette particular emphasis is placed
      on the use of transference interpretation derived from experience in the
      countertransference to address the defensive and expressive role of the dynamic
      movement of aliveness and deadness at a given juncture in an analysis. The role
      played by the experience of aliveness and deadness in the structure of the
      patient's internal object world and quality of object relatedness is examined.

PMID- 8543429
TI  - A particular perspective on impasses in the clinical situation: further
      reflections on psychoanalytic listening.
AB  - We tend to think of impasses as manifest, if often puzzling events, but they may
      also occur quietly, disguised. The analytic process may seem to be moving on
      course--yet, on further glance, there can be subtle evidence that some impasse,
      at times just emerging, may be, perhaps collusively, evaded. Often outside the
      patient's awareness, cues to its occurrence may be expressed in the vicissitudes
      of affect or state or shift in content. When such phenomena go unnoted as vital
      communications, ultimately, a more dramatic eruption may take place; or, perhaps
      more insidiously, some central conflictual feature of the patient's character
      continues unexamined, unabated. The author suggests an alteration in how we think
      about impasses--how pervasive they may be, even as we may believe we are seeing
      the ordinary ebbs and flows of resistances and defensive processes. Drawing upon
      four clinical examples, the effort is made to elucidate the link between our
      understanding and recognition of the presence of an impasse and our mode of
      analytic listening.

PMID- 8543430
TI  - Intersubjectivity in psychoanalysis: a critical review.
AB  - The intersubjective critique of the classical model's positivistic tradition is
      examined. Classical analysis construes the core of mental life as a discrete
      entity that can be relatively interpretively captured as such. In contrast, the
      intersubjectivists construe core psychic processes as inseparable from a
      relational matrix. The intersubjective critique is traced to the theoretical
      tensions in Freud's concepts of transference/countertransference and ego
      development. Questions are raised whether the current intersubjective challenges
      actually constitute changes in clinical activity and process. Noted is the
      ubiquitous overlap between the intersubjective and classical models in all
      theories of psychoanalysis, as each seem to capture different aspects of mental
      functioning. Classical analysis maintains a difference between a stultifying
      'idealisation' of a positivistically-based objective orientation and a holding
      such a possibility as only an 'ideal' to strive for: absolutist approaches to
      theory are unfounded, as the irreducibility of our subjectivity does not reduce
      us to total ignorance. Adopting an intersubjective orientation does not stop
      analysts from idealising 'that theory' and imposing it on the patient in an
      authoritarian manner. Nothing intrinsic to any theory forestalls self
      aggradisement, and answers to such problems may lie in other kinds of theoretical
      debates than these.

PMID- 8543431
TI  - 'Et in arcadia ego...?' Some notes on methodological issues in the use of
      psychoanalytic documents and archives.
AB  - The author uses archival material, mainly the letters exchanged between Jones and
      Strachey in the fifties, when Jones was writing his biography of Freud and
      Strachey was working on the Standard Edition. He shows the complexity of the
      interaction between these two men; the more or less conscious ambivalences,
      motivations and resentments against the so-called Freudian establishment of that
      time. This per se can help us to understand how a 'certain image' of Freud was
      created in Great Britain during those years and the reasons for its authoritative
      persistence. Yet the paper touches on more general issues such as those of the
      fascination with psychoanalytic archives and the more or less accepted and
      admitted unconscious motivations of the interpreters of these documents too, not
      excluding myself. The conclusion reached is that even psychoanalytical documents
      do not rest in a peaceful Arcadia and that archives cannot be considered as the
      Arcadia of documents--at least not in the ways that Arcadia has always been
      considered and interpreted, misleadingly, even in two paintings by Poussin, which
      I refer to in my paper. These in reality remind us that in Arcadia there is death
      too. Even the memory that the documents should help us to conserve is ineluctably
      bound to loss, dissemination, mutilation and uncertainty, and therefore must also
      face the presence of death also.

PMID- 8543432
TI  - Popularise and/or be damned: psychoanalysis and film at the crossroads in 1925.
AB  - Geheimnisse einer Seele'--the only film in which film producers and
      psychoanalysts have openly collaborated to bring psychoanalysis into the public
      domain--was an immediate success with the general public and reviewers and is
      still considered a milestone in the early history of the cinema. By contrast it
      caused disagreement within the psychoanalytic community, which put personal and
      professional relationships to a test, which Freud came to feel that 'our Circle
      has not passed well', and which has left the film as a millstone round the neck
      of psychoanalysis and its practitioners. By drawing on new documentary material
      and placing the 'Film Affair' in its wider context, the author aims to highlight
      the significance and complexity of this episode as an important event in the
      early history of psychoanalysis.

PMID- 8543433
TI  - The concept of psychic homosexuality.
AB  - The author examines the concept of psychic homosexuality, as it is used by French
      authors, based on Freud's ideas in The Ego and the Id (1923). Being intimately
      bound up with the organisation and development of psychic bisexuality in both
      sexes, psychic homosexuality is a concept that proves to have many meanings
      conceptually and in clinical use. In particular there is the question as to
      whether it is of the same kind and performs the same function in men as in women.
      Arguing that the primary relationship with the mother is crucial to the psychic
      organisation of the feminine and the masculine and that their fate is different
      in the development of the girl and the boy through to the structured
      identifications that result from the Oedipus complex, the author describes the
      case histories of a man and a woman. He concludes that psychic homosexuality
      might most usefully be considered not as a singular entity but as a set of plural
      entities. The advantage of this way of conceptualising things is illustrated in
      the way certain fantasy configurations connected with infantile sexual theories
      were able to be more richly understood. The author ends by drawing out some
      implications of these distinctions for technique.

PMID- 8543434
TI  - Love and the heritage of the past.
AB  - In this paper, the author explores the difficulties in developing the capacity to
      fall and remain in love, as shown in a case study of a Holocaust survivor's
      daughter whose mother lived through the Holocaust as a child. These difficulties
      arose from the inability of the daughter to go through the mourning processes
      necessary for the separation from her bereaved mother, as well as from the
      daughter's fixation on the mother's interminable, unresolved mourning. The
      daughter exploited her relationships with the love objects in her life to play
      the role of the victim/persecutor. She thus enacted the drama of facing death and
      being rescued through flight or promiscuity, elements which were dominant in her
      fantasies relating to her mother's past. The working through of the transference
      relationship helped her become aware of the unconscious meaning embedded in her
      actions and eventually lessened her need to live her mother's past in her own
      life.

PMID- 8543435
TI  - Creativity and the third age.
AB  - The paper discusses aspects of the creative process in the elderly and, indeed,
      in the old. After a definition of the third age, the writer goes on to discuss
      the nature and aims of creativity. Particular attention is paid to the roles of
      sexuality, regression in the service of the ego, narcissism, sublimation, the
      depressive position and reparation. There follows discussion on therapeutic work
      with creative elderly individuals.

PMID- 8543436
TI  - The problem of originality and imitation in psychoanalytic thought: a case study
      of Kleinian thinking in Latin America.
AB  - The author discusses some assumptions that are taken for granted when considering
      the discontent felt in Latin America with its psychoanalytical thinking, which is
      often characterised as the result of a colonised mentality which leads to
      imitation of European, especially British, ideas. The author criticises this
      explanation based on the opposition between the culture of the coloniser and the
      culture of the colonised. The author suggests that we start from another
      perspective, believing that the discontent which afflicts many Latin American
      analysts can be better understood by an analysis of how consumer societies treat
      knowledge that originates elsewhere. Consumer societies tend ruthlessly to
      simplify academic knowledge, rapidly transforming it into routine techniques
      ready for consumption. This treatment dislodges the knowledge from the conceptual
      schemes which generated it and which served as its source of inspiration. In this
      context certain consumer groups become owners of certain psychoanalytic ideas,
      simplified by the very use to which they are put. When ideas and theories become
      simplifications, mere techniques to be applied, they may be used to
      institutionalise and legitimate the domination of certain groups within local
      Psychoanalytic Societies. In this situation the remaining sectors of the local
      societies tend to treat these ideas as exotic and alien to their environment and
      the dominating groups foster the notion that it is the original, foreign power
      that is to blame for the colonising dominance of its ideas.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8543437
TI  - Charisma and attachment theory: a crossdisciplinary interpretation.
AB  - The attachment theory of Bowlby and his followers has not previously been applied
      to the interpretation of charismatic phenomena in the bonding of large numbers of
      people with their leaders in crisis. This essay, which builds on the author's
      'Surviving trauma: loss, literature and psychoanalysis', attempts to use
      attachment theory and sociological concepts such as homogamy, anomie, negative
      imprinting and de-individuation, as well as classical Freudian concepts such as
      transference and splitting of the ego, in interpreting the charismatic bond. It
      is argued that charismatic homogamy becomes viable at the point of intersection
      between the inner world of the charismatic leader and social and political
      reality. The bonding of the individual and the public may be based partly upon a
      symbolic link between public crisis and the charismatic's experience of trauma
      that has deeply scarred or even ended the affectional bonds in his family of
      orientation. This trauma, however, is a source of insight and power as well as of
      disability, for it has schooled him in crisis and given him the capacity to offer
      directional leadership. The charismatic and his society are bonded in crisis
      through a mutual attempt to break free of anomie and alienation, and a sense of
      powerlessness and despair.

PMID- 8543438
TI  - [Nutrition behavior in Germany].

PMID- 8543439
TI  - [Nutrition and metabolic syndrome].

PMID- 8543440
TI  - [Nutrition and cancer].

PMID- 8543441
TI  - [Food allergies].

PMID- 8543442
TI  - [Therapy of obesity].

PMID- 8543443
TI  - [Diet in hyperlipidemia, hypertension and gout].

PMID- 8543444
TI  - [74-year-old patient with sub-febrile temperatures, silent kidney and mid
      abdominal calcinosis].

PMID- 8543445
TI  - [Young man with swelling of the left side of the neck and right testis].

PMID- 8543446
TI  - [New non-benzodiazepine hypnotics. Progress in therapy of sleep disorders?].

PMID- 8543447
TI  - [Diagnosis of Alzheimer disease is probably made too frequently, ultimately from
      uncertainty of examination results].

PMID- 8543448
TI  - [Before administering oral anticoagulant therapy with vitamin K antagonists,
      should heparin be administered, even when therapy is purely of preventive intent
      without an acute clinical manifestation?].

PMID- 8543449
TI  - [Comments on the contribution by B. Noll. Aspirin and heparin in acute myocardial
      infarct].

PMID- 8543450
TI  - [Vertigo. The most frequent forms].

PMID- 8543451
TI  - AMA's role in the Medicare reform bill.

PMID- 8543452
TI  - Stark self-referral law.
AB  - Should Iowa physicians worry about the Stark law? Probably. In September, after a
      nearly four-year delay, the regulations for Stark I took effect. This article
      discusses how the Stark I and II self-referral laws might affect your practice.

PMID- 8543453
TI  - Prostate cancer management in older patients.

PMID- 8543454
TI  - Learning from our legal colleagues.

PMID- 8543455
TI  - Changes in therapy in a changing reality.

PMID- 8543456
TI  - The familiar and the strange: the dynamics of change.
AB  - This article relates to curative factors in the therapeutic process, or, to be
      more precise, to the various modes of the therapist's presence as presumed
      factors of change. It points to factors of change that have been discussed at
      length in the various streams of the analytical literature, which emphasized
      passive attention, absorption, processing and interpretation on the analyst's
      part, in an atmosphere of restraint and understanding (factors such as "free
      floating attention," "empathy," etc.). It stresses the importance of another
      psychic function different in nature--"defamiliarization"--as a condition that
      facilitates and accompanies processes of understanding and changes in perspective
      in relation to a reality aesthetically mediated by every human work of art, in
      general, and in relation to the personal-inner reality as it is expressed in the
      therapeutic work of art, in particular. This term sheds light on an active,
      mobile, breaking away--distancing--and rebinding aspect in the psychic
      functioning of the therapist (and in parallel of the patient), which allows them
      to "see the new" in a (supposedly) very familiar emotional given. In my view,
      this term joins others such as "act of freedom" and "constructive listening" in
      deepening our understanding of the therapeutic factor. There is reference to the
      term "defamiliarization," or "making strange," in its natural context--its
      birthplace--in literary criticism, and in a different historical context--in two
      key articles of the thirties that related to the causes of change in therapy in a
      very different way.

PMID- 8543457
TI  - Treating the love-sick patient.
AB  - Love-sick patients come to therapy because they are suffering from an obsession.
      Their lover has left, apparently for good. They cannot accept this fact, mourn
      the loss and get on with life. Object relations theory offers a framework for
      better understanding their suffering. The patients described have experienced
      early relationship disturbances, and their adult love offered an illusory defence
      against deep feelings of fragility and low self-esteem. Accepting the finality of
      their lover's departure meant re-experiencing feelings of abandonment and
      worthlessness. An effective psychodynamic strategy in cases like these is to
      focus on these painful feelings, particularly as they appear in the therapy
      relationship. Learning to tolerate them in this relationship can be a positive
      step towards accepting the lover's departure.

PMID- 8543458
TI  - The role of affects in the process of change in psychotherapy.
AB  - Questioning the place of the notion of change in psychoanalytic theory and
      therapy, this essay tries to compare it with its homologue in change-focused
      theories, a comparison that shows an inverse relation between theoretical
      richness and an atheoretical stance oriented explicitly toward change. It is
      suggested that the concept of affect provides notions of flowing that are needed
      in structurally biased psychoanalytic theory, and that from a therapeutic point
      of view, an emotional relationship between the therapeutic partners endows
      interpretations with mutative power. Two dimensions of affects in therapy are
      discussed: emotional accompaniment and emotional restructuring. It is further
      suggested that the double-edgedness of affects accounts for the emotions
      "grasping" the "nucleus of change" both from the inside and from the outside, and
      that the process of change uses the function of emotions as motives to change
      something in their function as indicators and signifiers of situations.

PMID- 8543459
TI  - The couple and the psychotherapeutic group.
AB  - In some situations, when two spouses participate in the same psychotherapeutic
      group, we find that the group, in order to function, threatens the individual and
      the couple "envelope." As a result, defenses become rigid and the therapeutic
      process is blocked, as illustrated by two clinical vignettes. Based on this
      approach, the characteristics of couples for whom participation in a couple group
      is contraindicated are conceptualized. In order to prevent the formation of a
      process in which defenses are hardened, leading to the blocking of therapy, and
      to exploit the positive potential found in the therapeutic group, an alternative
      model is proposed in which the spouses are treated in two sub-groups
      simultaneously.

PMID- 8543460
TI  - Two kinds of change facilitating factors.
AB  - A wide variety of conceptualizations exists to account for the facilitation of
      change in psychotherapy. These are usually related to advances in
      psychopathological and/or developmental formulations. The approach to the subject
      usually follows causal logic, in the spirit of the medical model. The present
      paper argues that although causal factors operate in psychotherapeutic practice,
      alongside them there is a class of non-causal factors whose impact and
      contribution to therapeutic progress should not be underestimated. The
      paradoxical effect of these factors may be better understood if we examine those
      features that pertain not to focal "psychotherapeutic action," but to what
      enables it, namely to the background factors inherent in the psychotherapeutic
      situation. Of these, abstinence and constancy are two factors singled out for
      discussion. With the help of clinical vignettes, it is illustrated how these two
      controversial psychotherapeutic tenets contribute decisively to the creation and
      management of the psychotherapeutic endeavor. These contributions are discussed
      and elaborated in light of two experiential modalities, of Being and Doing, which
      provide a framework for the coexistence and conjoint effectiveness of causal and
      non-causal factors in individual functioning and development, as well as in
      psychotherapeutic practice.

PMID- 8543461
TI  - Self-critical and dependent aspects of loneliness.
AB  - In this study, the concept of loneliness is examined in relation to different
      types of depression. The Depressive Experience Questionnaire and the short form
      of the Revised UCLA Loneliness scale were administered to 70 normal subjects.
      Both anaclitic and introjective factors of depression were found to be
      significantly related to loneliness. Contrary to expectations self-critical
      (introjective) depression accounted for twice the variance of the loneliness
      measure than dependent (anaclitic) depression. Introjective depression as an
      integral component of the inner dynamic of loneliness is discussed.

PMID- 8543462
TI  - Changes in the therapist's working theory.
AB  - Theory, a system of ideas aimed at explaining clinical data, has in
      psychoanalysis (and in psychotherapy) a preponderant and subjective status in the
      mind of the analyst. It is a part of the conscious and unconscious world of the
      analyst and intertwines with his personality. A free, fluent therapeutic process
      demands a constant dialectical movement between theory and practice. Dogmatic or
      rigid application of theory, or its ever possible use as a defence or counter
      resistance, freeze the dialectical movement. Two short vignettes illustrate the
      use and misuse of theory. The discussion focuses on how to bring together the
      vertex of the analyst and the vertex of the patient, the already-known
      theoretical knowledge with the not-yet-known discourse of the patient. Free
      floating theorization (Aulagnier) enables a bridging of the gap and will make a
      flexible use of theory possible.

PMID- 8543463
TI  - Time course and concentration dependence of the incorporation of
      deuterated/tritiated arachidonic acid and derived fatty acids in THP-1 cell
      lipids.
AB  - We have supplemented THP-1 cells, a human monocytic leukemia cell line, with
      arachidonic acid (AA), containing [3H8] AA, 1-25 microM, for up to 24 hours, and
      explored the time and concentration dependent patterns of incorporation in cell
      lipid classes and subclasses. Twenty-five microM AA consisted of deuterated AA
      ([2H8] AA), containing also [3H8] AA. Phospholipids (PL) were separated by HPLC
      with UV and radiodetection, and the fatty acids (FA) methyl esters were analyzed
      by GC. [2H8] AA pentafluorobenzyl-esters from individual lipid classes were
      obtained and analyzed by GC-MS. Incorporation of AA in cell lipids increased
      linearly with increasing concentrations, whereas 22:4 and 22:5 accumulated only
      at 25 microM AA. Up to 10 microM AA, more than 95% of the FA was incorporated in
      PL, whereas at 25 microM AA a significant proportion of the exogenous FA was
      incorporated in triglycerides (TG) and in diacyl phosphatidylcholine (PC). The
      time-course of AA incorporation showed that the peak was at 3 hours, with minimal
      incorporation in TG, in the presence of 5 microM, whereas the peak occurred at 6
      hours, with about 50 percent incorporation in TG, with 25 microM. The data
      indicate that the range of AA concentrations and the time course of the
      incorporation of this FA in cell structural lipids are critical.

PMID- 8543464
TI  - Glucocorticoid receptors in depression.
AB  - During major depression, dysfunction of limbic structures resulting in
      hypersecretion of corticotropin-releasing factor (CRF) is believed to cause the
      well-known hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in this
      disorder. Nonsuppression of the HPA axis by dexamethasone in depressed patients
      suggest that this increased CRF secretion may be due, at least in part, to
      altered feedback inhibition by glucocorticoids. Because glucocorticoid-induced
      feedback inhibition of the HPA axis is mediated by glucocorticoid receptors (GRs)
      in the brain and pituitary, the possibility that depression is associated with a
      primary alteration in GRs number and/or function has been an important
      consideration regarding the pathophysiology of the depressive disorders.
      Nevertheless, studies investigating GRs kinetics in depressed patients have been
      inconsistent. In some studies, decreased GRs number in depressed patients has
      been observed; others have obtained discordant results. The inconsistency of
      results may be due to a number of factors, including patient heterogeneity, the
      cell populations sampled, and the methods used to determine receptors number.
      Fewer studies have investigated the functional sensitivity of cells to the
      inhibitory effects of glucocorticoids, but they have been more consistent,
      showing increased resistance of cells from depressed patients to the inhibitory
      effects of glucocorticoids on immune function. In view of intriguing data
      indicating monoamine regulation of GR number and function in a hormone
      independent fashion along with the well-known effects of glucocorticoids on
      behavior, further scrutiny of the role of GR in depression and its treatment is
      warranted.

PMID- 8543465
TI  - Insulin-like growth factors (IGFs) and IGF-binding proteins in diabetic kidney
      disease.

PMID- 8543467
TI  - Japan--Israel Joint Meeting in Neurosciences. Recent developments and future
      perspectives in studies of brain mechanisms. Eilat, Israel, December 14-17, 1994.
      Abstracts.

PMID- 8543466
TI  - 4th Annual meeting of the Israel Society for Neurosciences. Eilat, Israel, 10-13
      December 1995. Abstracts.

PMID- 8543468
TI  - Total quality management: field of dreams?
AB  - Total quality management promises to reconcile cost/quality conflicts, increase
      customer satisfaction, and improve hospitals' competitiveness as well as
      operational and financial performance. This article reviews the hospital
      literature on TQM and concludes that there is little evidence to substantiate
      these claims. The article concludes with implications for research and
      management.

PMID- 8543470
TI  - The development of integrated service networks in Minnesota.
AB  - The formation of health insurance purchasing alliances in Minnesota has caused a
      restructuring of the provider system. One of the results has been the formation
      of competing delivery systems that organize hospitals, physicians, and insurance
      plans into vertically and horizontally integrated organizations termed integrated
      service networks (ISNs). This article describes the formation of these ISNs and
      identifies some of the salient features that distinguish them from other provider
      systems.

PMID- 8543471
TI  - Agency theory: a framework for analyzing physician services.
AB  - The principles of agency theory and how the theory can be used as a framework for
      the design of physician selection procedures and of physician compensation
      contracts and control systems for the regulation of physician practices are
      discussed. The theory is used to show why third party payers who wish to control
      expenditure for high quality health care may be better off if they enter into
      salary contracts rather than fee-for-service or capitation contracts with
      individual physicians.

PMID- 8543472
TI  - The challenges of governing integrated health care systems.
AB  - As health care delivery organizations develop into integrated health care
      systems, new and significant challenges arise with respect to how such systems
      should be governed. This article explores several key governance issues that
      organizations are likely to encounter as they attempt to effect the transition
      from hospital or multihospital system governance arrangements to those
      appropriate for integrated systems.

PMID- 8543473
TI  - The implementation of total quality management in hospitals: how good is the fit?
AB  - Total quality management has become popular among hospitals because of its
      promise to reconcile trade-offs between cost and quality. However, assumptions
      inherent in TQM may not translate to the hospital environment: hierarchical
      management control over the technical core and the dominance of rational decision
      making. This article considers these two assumptions and suggests that the
      application of TQM to hospitals take them into account because they may
      compromise its success.

PMID- 8543474
TI  - Some aspects of occupational safety and health in green tea workers.
AB  - The objectives of this study were to evaluate the health and safety conditions of
      36 male and 27 female green tea workers who were aged 40-69 years and had worked
      for at least 5 years in green tea production procedures. The Mean +/- SD of age
      was 57.1 +/- 5.8 years in males and 54.4 +/- 6.4 years in females. The mean
      working career was 26.1 +/- 9.5 years and 24.3 +/- 9.1 years, respectively. The
      most commonly subjective complaints developed while at work was pain in the lower
      back at a rate of 72.2% in males and 63.0% in females. Regarding persistent
      subjective complaints, female workers had significantly (P < 0.05) higher
      prevalence rate for breath shortness (25.9%) compared to that of male workers
      (5.6%). It was observed that the male workers whose occupational career was equal
      to or more than 28 years had significantly higher prevalence rates for stiffness
      in the neck and pain in the arms, compared to those of male workers whose
      occupational career was less than 28 years. The prevalence of nasal allergy was
      11.1% either in the male or female workers. The total rate of accidents during
      working hours in the male workers was 22.2%, and that in the female subjects was
      18.5%. The mean frequency weighted vibration magnitude produced by using tea-leaf
      plucker was in the range of 2.4-3.5 m/s2. The mean equivalent A-weighted noise
      level while using the same equipment was 100.6 +/- 5.0 dB(A). The need for
      occupational safety and health programs in these small farm settings are
      discussed.

PMID- 8543475
TI  - Acute effects of inhalation exposure to carbon monoxide on schedule-controlled
      operant behavior and blood carboxyhemoglobin levels in rats.
AB  - The acute effects of carbon monoxide (CO) exposure on a steady-state operant
      behavior (bar-pressing under a VI 60-sec schedule of food reinforcement) were
      repeatedly measured in (a) rats exposed to various concentrations of CO (500,
      1,000, 1,500 and 2,000 ppm) for 1 h and (b) rats exposed to 1,500 ppm for
      different periods (1, 2 and 4 h). Measurements were made continuously before,
      during and after the exposure period. Abrupt cessation of the response was
      produced by exposure to 1,000 ppm or higher concentrations of CO. Recovery from
      the effects of CO exposure was observed as sudden resumption of responding during
      the post-exposure period. The duration of exposure required to produce response
      inhibition was closely correlated with the exposure concentration. The post
      exposure interval required for response recovery was also correlated with the
      exposure concentration. This post-exposure response recovery interval, however,
      was constant and independent of the duration of exposure when the concentration
      was fixed at 1,500 ppm. In order to correlate these behavioral changes with an
      internal index of CO exposure, blood carboxyhemoglobin (HbCO) levels were
      determined under several exposure conditions corresponding to those of the
      behavioral observations. It was found that HbCO levels were within a certain
      range (33-43%) when response recovery occurred, suggesting the existence of a
      critical HbCO level (threshold) associated with the drastic behavioral change.
      Hence, these results support the view that blood HbCO is an important determinant
      of the acute behavioral effects of CO.

PMID- 8543476
TI  - Effect of long and short fibre amosite asbestos on in vitro TNF production by rat
      alveolar macrophages: the modifying effect of lipopolysaccharide.
AB  - The influence of long and short fibre amosite on the generation of tumor necrosis
      factor (TNF) by rat alveolar macrophages was investigated in vitro. TNF rich
      supernatants were prepared from macrophages cultured in F10 medium +2% Bovine
      Serum Albumin (BSA). Spontaneously released TNF from unstimulated macrophages and
      TNF rich supernatants from macrophages exposed to Lipopolysaccharide (LPS) and
      fibres were stored at -70 degrees C and then tested for their cytotoxicity
      towards L929 cells. Maximum spontaneously released TNF was obtained from 24 hour
      macrophage cultures. Short amosite fibres had no significant effect in
      stimulating alveolar macrophages to release TNF while the 50 micrograms dose of
      long fibres resulted in significantly increased release of TNF. Cotreatment of
      alveolar macrophages with LPS and fibres further enhanced the TNF production and
      maximum production was obtained with LPS +50 micrograms dose of long fibre
      resulted in significantly increased release of TNF. Co-treatment of alveolar
      macrophages with LPS and fibres further enhanced the TNF production and maximum
      production was obtained with LPS +50 micrograms of long fibre amosite. The
      present study indicates that fibre dimension is a major factor in in vitro dust
      activity and TNF has a possible active role to play in dust induced inflammation
      in vivo.

PMID- 8543477
TI  - Exacerbation of nickel induced oxidative response by vitamin E.
AB  - Vitamin E (alpha-tocopherol), a well known naturally occurring chain breaking
      antioxidant and a free radical scavenger was found to exacerbate nickel (Ni)
      toxicity in mice. Vitamin E (Vit. E) mediated enhancement of nickel toxicity was
      demonstrated by (i) enhanced mortality in mice treated with Ni and Vit. E (ii)
      increased hepatic lipid peroxidation, (iii) increased rate of benzoate
      hydroxylation, and (iv) liposomal membrane damage.

PMID- 8543478
TI  - Vibrotactile temporary threshold shifts induced by hand-transmitted vibration
      during underwater work.
AB  - The purpose of this paper is to clarify the temporary threshold shifts (TTS) of
      fingertip vibratory sensation produced by hand-transmitted vibration in an
      underwater work environment. The hand-transmitted vibration was applied with a
      pneumatic tool to the right hand of four experienced male SCUBA divers. The
      threshold of 125 Hz vibratory sensation was measured at the tip of the right
      forefinger before and after vibration exposure in the atmosphere and underwater.
      Vibration exposure at a 4 m depth produced greater TTS than in the atmosphere.
      The recovery time of TTS after vibration exposure in an underwater were affected
      by the underwater pressure.

PMID- 8543479
TI  - Consistency of the first fixation when viewing a standard geometric stimulus.
AB  - Eye movements in response to presentation of a standard geometric figure (Rey
      Complex Geometric Figure) were investigated in 33 normal subjects. The figure was
      presented to each subject for 20 s, with instructions to remember as much detail
      as possible. Stimulus display was managed by special software that ensured all
      subjects were focused on the centre of the monitor before presentation, thus
      controlling for the initial point of gaze. Subjects were instructed, after
      viewing the stimulus, to reproduce the figure to scale on a blank sheet of paper.
      Location of the first voluntary fixation during the viewing period was
      consistently near the same feature in 80% of subjects (cohort I, n = 20).
      Patterns of eye movement during the remainder of the period, however, were found
      to vary widely among individuals. A complementary experiment using a second group
      of subjects (cohort II, n = 13) was undertaken to examine possible effects of
      brain function lateralisation on processing a feature in the left hemi-field. No
      lateralisation effect was evident and consistent identification of the same
      feature in the first voluntary fixation was confirmed for all subjects. No
      systematic relationships were found between eye movement indices obtained from
      real-time viewing of the Rey Figure and subsequent recall by drawing.

PMID- 8543480
TI  - Effect of spatial ability and sex on EEG power in high school students.
AB  - Performance at eight cognitive tests and EEG spectral power at rest was computed
      in 2 groups of men and women, between 17 and 21 years of age, with extreme
      degrees of spatial ability (SA) evaluated by the spatial relations subtest of the
      DAT: a low spatial ability group (10 men, 10 women) with scores below percentile
      30 and a high spatial ability group (10 men, 10 women) with scores above
      percentile 80. Ten EEG artifact free samples, 4.096 sec each, were analyzed and
      absolute (AP) and relative power (RP) were obtained for 5 frequency bands using
      an FFT. EEG was submitted to principal component analysis and two way ANOVAs.
      High SA showed lower AP in the entire spectrum with eyes open and closed, and
      lower alpha 1 RP with eyes open than low SA group regardless of sex. The
      difference between low and high SA was better explained by high alpha AP at all
      derivations and high theta AP at right derivations and at left central and
      occipital regions. Women showed higher beta 1 and beta 2 AP at all derivations
      except at temporal regions than men regardless of SA scores.

PMID- 8543481
TI  - Decelerative changes in heart rate during recognition of visual stimuli: effects
      of psychological stress.
AB  - The present study investigated whether the anticipatory heart rate (HR)
      deceleration response may reflect a pre-attentive process of stimulus
      registration and how reaction time (RT) and HR responses are influenced by the
      introduction of a psychological stressor. 60 subjects participated in a signalled
      RT task with a feedback stimulus containing information on their reaction time
      and accuracy. Changes in HR, skin conductance (SC) and respiration activity were
      monitored during performance in two conditions of a visual stimulus recognition
      task with a fixed foreperiod. In one condition subjects were informed that some
      electric shocks would be delivered to their right wrist (stress condition); in
      the other, subjects were simply engaged in the stimulus recognition without the
      stressor (no-stress condition). Stimuli consisted of geometrical figures and for
      each trial subjects were required to determine whether a probe stimulus was the
      same as or different from one of two memory items. Two reliable anticipatory HR
      decelerations, one preceding the imperative stimulus and the other preceding the
      feedback signal, were observed. Because the HR deceleration preceding the
      feedback signal (that did not require the inhibition of any specific motor
      response) was more pronounced than that obtained for the probe stimulus, it was
      concluded that HR deceleration response is an expression of stimulus processing
      rather than response preparation. Reaction times for 'same' stimuli were shorter
      than for 'different' stimuli. Averaged respiratory activity showed that with the
      onset of a warning signal subjects inspired and held their breath until they
      received the feedback signal. The averaged skin conductance data showed two main
      phasic increases, one after the probe stimulus onset and the other after the
      delivery of the feedback signal. This was taken to reflect the orienting response
      to the most significant stimuli.

PMID- 8543482
TI  - Hippocampal event-related potentials to pitch deviances in an auditory oddball
      situation in the cat: experiment I.
AB  - Hippocampal event-related potentials (ERP) in the areas CA1, CA3, and dentate
      fascia (Df) were recorded in cats during an oddball situation when pitch deviant
      tones occurred in a series of standard tones. When difference waves were
      calculated by subtracting ERPs to the standard tones from those to the deviant
      tones, no clear N40d, corresponding to a cat analogue of the human mismatch
      negativity (MMN) observed in earlier studies, could be detected. Instead, a
      prominent later negativity (N130d) was observed. A possible extra-hippocampal
      source of the process reflected by the MMN-like negativity, and a relation
      between an orienting response (OR) and the N130d are discussed.

PMID- 8543483
TI  - Behavioral and hippocampal evoked responses in an auditory oddball situation when
      an unconditioned stimulus is paired with deviant tones in the cat: experiment II.
AB  - Event-related potentials (ERP) in the areas CA1, CA3 and dentate fascia (Df) of
      the hippocampal formation were recorded during an oddball situation in the cat. A
      rewarding electrical stimulation of the lateral hypothalamus (US) was paired with
      deviant tones (2500 Hz) that occurred randomly in a series of the standard tones
      (2000 Hz) given to the left ear. In addition to developing orienting head
      movements to the side of the deviant tones, an increase in the amplitude of
      parallel hippocampal ERPs was observed. Both the behavioral and neural responses
      appeared not until a 50 ms latency range. Furthermore, time-amplitude
      characteristics of the ERPs corresponded to time-acceleration characteristics of
      the conditioned orienting head movements. The results are discussed in the
      context of a cat analogue of the human mismatch negativity (MMN) and a role of
      the hippocampal formation to model and predict the conditioned behavioral
      orienting responses.

PMID- 8543484
TI  - Cardiorespiratory response under combined psychological and exercise stress.
AB  - The effects of combined physical and psychological stress on cardiovascular and
      respiratory responses were examined. Thirty-six undergraduate men performed a
      mental arithmetic task and moderate aerobic exercise, separately and in
      combination, while physiological measures were recorded continuously using
      electrocardiography, impedance cardiography, and respiratory gas analysis
      techniques. Cardiovascular responses during the combination of exercise and
      mental arithmetic stress were greater than those during either stressor alone,
      indicating that exercise did not mask the increases in cardiovascular performance
      evoked by psychological stress. In contrast, respiratory responses to the
      combined stressor were greater than those during isolated mental arithmetic, but
      less than those during isolated exercise. Thus the results indicate that physical
      and psychological stress exert a synergistic impact on cardiac performance, but
      not necessarily on respiratory performance. The results are consistent with the
      notion that the cardiovascular response to acute psychological stress exceeds
      concurrent metabolic demands.

PMID- 8543485
TI  - On the relationship between EEG and ERP variability.

PMID- 8543486
TI  - Meropenem: a microbiological overview.
AB  - Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal
      activity in vitro against almost all clinically significant aerobes and
      anaerobes. Its high activity is explained by ease of entry into bacteria combined
      with good affinity for essential penicillin binding proteins, including those
      associated with cell lysis. Breadth of spectrum is due, in part, to stability to
      all serine-based beta-lactamases, including those which hydrolyse third
      generation cephalosporins. Meropenem has an antibacterial spectrum which is
      broadly similar to that of imipenem but, whilst slightly less active against
      staphylococci and enterococci, it is more active against Pseudomonas aeruginosa,
      all Enterobacteriaceae and Haemophilus influenzae. Amongst common human
      pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are
      uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant
      Streptococcus pneumoniae are higher than for penicillin-susceptible strains but
      the organisms remain susceptible. Clinical susceptibility in vitro to meropenem
      is defined by MICs of < or = 4 mg/L, intermediate susceptibility by MICs of 8
      mg/L and MICs of > or = 16 mg/L define resistance; equivalent figures for zones
      of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or =
      11 (resistant) mm. Studies in guinea pig models of systemic infection and
      infections localised to the lungs, urinary tract and the central nervous system,
      some of which used immunocompromised animals, confirm the potential of meropenem
      demonstrated in vitro. These factors, combined with the human plasma, tissue or
      urinary concentrations of meropenem which exceed modal MICs for the pathogens
      isolated in clinical trials for most or all of the recommended 8 h dosing
      interval, predict that meropenem should be efficacious in the treatment of
      infections at many body sites.

PMID- 8543487
TI  - Intramuscular meropenem in the treatment of bacterial infections of the urinary
      and lower respiratory tracts. Italian Intramuscular Meropenem Study Group.
AB  - In three open, multicentre, prospective randomised studies, the efficacy and
      safety of meropenem were assessed and compared with ceftazidime (Study 1) and
      imipenem/cilastatin (Studies 2 and 3) in 864 patients; 417 with urinary tract
      infections (UTI) and 447 with community acquired lower respiratory tract
      infections (LRTI). All the antibiotics were administered by intramuscular
      injection. Clinical and bacteriological responses were assessed at the end of
      therapy and at follow-up (2-4 weeks for LRTI, 4-6 weeks for UTI). The clinical
      response rate in UTI at the end of therapy was 93-100% for meropenem 500 mg tds
      compared with 94-95% for ceftazidime 500 mg tds; for meropenem 500 mg bd it was
      97%, significantly higher than that for imipenem/cilastatin 500 mg bd which was
      90% (P = 0.03). At follow-up, the response rates were 90% for meropenem tds
      compared with 81-85% for ceftazidime 500 mg tds and 81% for meropenem bd compared
      with 78% for imipenem/cilastatin 500 mg bd. The clinical response rate in LRTI at
      end of therapy was 93% for meropenem 500 mg tds, compared with 92% for
      ceftazidime 1 g tds; for meropenem 500 mg bd the clinical response rate was 96%,
      compared with 91% for imipenem/cilastatin 500 mg bd (P = 0.054). At follow-up,
      the clinical response rates were 96%, 89%, 93% and 96%, respectively. The
      bacteriological response rates at 5-9 days post-therapy in UTI were 61-84% in
      patients treated with meropenem 500 mg tds, compared to 73-82% in patients
      treated with ceftazidime 500 mg tds; the rates for meropenem 500 mg bd and
      imipenem/cilastatin 500 mg bd were each 75%. At follow-up, the response rates
      were 40-72%, 57-70%, 51% and 49%, respectively. In LRTI, bacteriological response
      rates at the end of therapy were 91% for both meropenem 500 mg tds and
      ceftazidime 1 g tds, and 91% for meropenem 500 mg bd compared with 86% for
      imipenem/cilastatin 500 mg bd. At follow-up, the response rates were 87%, 77%,
      84% and 79%, respectively. All treatments were well tolerated. In these studies,
      intramuscular meropenem proved to be an effective and well tolerated treatment
      for LRTI and UTI.

PMID- 8543488
TI  - Treatment of acute bacterial exacerbations of chronic obstructive pulmonary
      disease in hospitalised patients--a comparison of meropenem and
      imipenem/cilastatin. COPD Study Group.
AB  - Meropenem and imipenem/cilastatin were compared in an open, randomised
      prospective multicentre study in the treatment of acute exacerbations of severe
      chronic obstructive pulmonary disease in hospitalised patients. One-hundred-and
      seventy-three patients were enrolled; 164 were evaluable for clinical efficacy
      and 98 for bacteriological efficacy, with 144 pathogens isolated. The predominant
      pathogens were Haemophilus influenzae (n = 30), Streptococcus pneumoniae (18),
      Staphylococcus aureus (12), Pseudomonas aeruginosa (11), Moraxella catarrhalis
      (8), other Gram-negative bacteria (Neisseria, Klebsiella, Proteus, and
      Enterobacter spp.) (53) and other Gram-positive bacteria (12). A single bacterial
      pathogen was identified in 61 patients, whereas two bacterial pathogens were
      isolated in 31 patients and three in six patients. The clinical response at the
      end of treatment was very high in both groups with a satisfactory outcome (cured
      or improved) in 97.6% of the meropenem patients and in 96.3% of the
      imipenem/cilastatin patients; at follow-up the rates were 89.1% and 89.8%,
      respectively. The bacterial success (eradication or presumed eradication) was
      88.2% in the meropenem group and 89.4% in the comparator group. Nausea or
      vomiting were reported more frequently in patients treated with
      imipenem/cilastatin, whereas in the meropenem group an increase in
      aminotransferases was reported. One patient treated with imipenem/cilastatin was
      withdrawn from the study due to seizures. Meropenem and imipenem/cilastatin were
      highly effective for the treatment of severe bacterial exacerbations of chronic
      bronchitis but meropenem was better tolerated.

PMID- 8543489
TI  - Clinical evaluation of meropenem versus ceftazidime for the treatment of
      Pseudomonas spp. infections in cystic fibrosis patients.
AB  - Cystic fibrosis patients (children and young adults) with Pseudomonas spp. chest
      infections were treated with meropenem or ceftazidime. This study was the first
      to investigate the use of meropenem in cystic fibrosis. Meropenem was well
      tolerated with only transient elevations of serum transaminases. No patient
      experienced nausea and vomiting, even when meropenem was administered as a bolus
      injection. This allowed home therapy to be used. Meropenem appeared to be at
      least as active as ceftazidime even at the low doses used. Patients showed a
      greater improvement in respiratory function on meropenem than ceftazidime. Only
      one patient (out of 60 courses) failed to respond to meropenem (98% success rate)
      compared with two failures out of 21 episodes with ceftazidime (90% success
      rate). There was little emergence of resistance to meropenem even though some
      patients were treated up to eight times over a 2 year period.

PMID- 8543490
TI  - Empirical monotherapy with meropenem in serious bacterial infections. Meropenem
      Study Group.
AB  - A multicentre, open, randomised, parallel group study was carried out to assess
      the efficacy and safety of meropenem monotherapy versus the combination of
      ceftazidime plus amikacin in the treatment of serious bacterial infections.
      Adult, hospitalised patients (n = 237) were included if they had infections at
      one or more of the following sites: lower respiratory tract (89 community
      acquired; 84 hospital-acquired), urinary tract (59 complicated; 3 uncomplicated),
      skin and skin structures (n = 8), or septicaemia (n = 29). Patients were
      randomised to receive either iv meropenem (1 g every 8 h) as monotherapy or iv
      ceftazidime (2 g every 8 h) plus iv amikacin (15 mg/kg/day in two or three
      divided doses). Meropenem had comparable clinical efficacy to ceftazidime plus
      amikacin in: community-acquired lower respiratory tract infection (LRTI) (40/43,
      93% vs 31/39, 79% cured or improved); hospital-acquired LRTI (30/37, 81% vs
      23/32, 72%); septicaemia (10/12, 83% vs 16/17, 94%) and complicated urinary tract
      infection (UTI) (13/15, 87% vs 25/25, 100%). A similar proportion of patients in
      each treatment group experienced adverse events, the most frequent being
      transient elevations in serum transaminases. Seven patients in the meropenem
      group and eight patients in the ceftazidime plus amikacin group died during the
      study period from reasons unrelated to study medication, and seven patients (five
      meropenem, two ceftazidime plus amikacin) were withdrawn due to adverse events.
      Empirical monotherapy with meropenem is as well tolerated and as effective as the
      combination of ceftazidime plus amikacin in the treatment of serious infections.

PMID- 8543491
TI  - Safety and efficacy of meropenem in patients with septicaemia: a randomised
      comparison with ceftazidime, alone or combined with amikacin.
AB  - Meropenem is a new broad spectrum carbapenem antibiotic which can be administered
      as monotherapy for serious infections. The efficacy and safety of meropenem was
      compared with that of ceftazidime (alone or in combination with amikacin) in 153
      patients with septicaemia who were enrolled into identical, prospective,
      randomised studies. Forty-five patients with infections arising from the urinary
      or lower respiratory tracts were given either meropenem 500 mg or ceftazidime 250
      1000 mg intravenously every 8 h; 108 patients with more serious infections were
      given meropenem 1 g or ceftazidime 2 g every 8 h +/- amikacin 15 mg/kg/day.
      Overall, 71 patients received meropenem, 47 ceftazidime and 35 ceftazidime plus
      amikacin. Comparable clinical response rates were achieved in the meropenem and
      ceftazidime/amikacin groups (92% vs 94% at the end of therapy respectively).
      Furthermore, a satisfactory bacteriological response was obtained in all
      evaluable patients. The most common pathogens isolated were Escherichia coli,
      Streptococcus pneumoniae and Pseudomonas aeruginosa. Relapse occurred in one
      patient in the ceftazidime/amikacin group, who had a mixed infection of E. coli
      and P. aeruginosa. There were no relapses in the meropenem group. Both treatments
      were well tolerated and only one patient had to withdraw from the trial because
      of an adverse effect (rash associated with ceftazidime). In conclusion, these
      data confirm that meropenem monotherapy is well tolerated and is as effective as
      ceftazidime (alone or combined with amikacin) in the empirical treatment of
      septicaemia. It should prove to be a useful addition to the drugs currently
      available for this life-threatening disease.

PMID- 8543492
TI  - Anti-infective strategies in neutropenia.
AB  - Anti-infective strategies in febrile neutropenic patients have evolved
      continuously over the past decade. The changing spectrum of not only the
      infecting organisms but also of the underlying disease have necessitated
      different approaches. While the duration and degree of neutropenia have remained
      the most important risk factors for the development of invasive infections, other
      factors such as the presence of catheters, cytotoxic chemotherapy, mucositis,
      infection history, microbial colonisation and the concomitant immune dysfunction,
      also play a major role in the design of the anti-infective strategy.
      Individualisation of treatment strategy and the need for flexibility in response
      to local microbial ecology have also become key concepts. Controversy still
      surrounds the optimal prophylactic and empirical therapeutic regimens. Selective
      suppression of the endogenous microbial flora, particularly of the alimentary
      tract and other mucosal surfaces is recommended for high risk patients, such as
      those with anticipated profound and prolonged neutropenia, severe post
      chemotherapy mucositis and the presence of long-term intravenous catheters. For
      all other risk categories, cost benefit ratios must be carefully weighed against
      potential clinical benefit. Empirical monotherapy with broad-spectrum
      cephalosporins or a carbapenem is accepted as a cost-effective and usually well
      tolerated alternative to combination therapy. However, close monitoring of the
      patient's response is essential. Early empirical antifungal therapy also remains
      one of the prerequisites for a successful outcome in the management of
      neutropenic fever. Safer and more effective antifungal agents are urgently
      needed. In the future haematopoietic growth factors and other new techniques,
      such as peripheral blood progenitor cell transplantations, are likely to play a
      role in the early prophylaxis and management of severe neutropenic infective
      episodes. Future anti-infective strategies in the neutropenic host may not only
      lie with antibiotics, but also encompass successful modulation of host defences.

PMID- 8543493
TI  - Antibiotic monotherapy with meropenem in the surgical management of intra
      abdominal infections.
AB  - In an open, multicentre, randomised study, the efficacy and safety of meropenem
      monotherapy as adjuvant antibiotic therapy in the surgical management of intra
      abdominal infection was compared with that of the combination of cefotaxime and
      metronidazole. A total of 160 hospitalised adult patients with intra-abdominal
      infection requiring surgery were treated intravenously with either meropenem 1 g
      every 8 h (by bolus injection or infusion; n = 77) or cefotaxime 2 g and
      metronidazole 500 mg every 8 h (n = 83). Clinical and bacteriological responses
      to antibiotic therapy were assessed at the end of treatment and at 2-4 weeks'
      follow-up after treatment. The clinical response rates at the end of treatment
      and follow-up were 91% and 96%, respectively, for meropenem and 100% and 97%,
      respectively, for cefotaxime plus metronidazole. The bacteriological response
      rates were 90% and 93%, respectively, for meropenem and 92% at both time points
      for cefotaxime plus metronidazole. Both treatments were well tolerated. In this
      study, meropenem monotherapy was effective and as well tolerated as cefotaxime
      plus metronidazole. Meropenem monotherapy should, therefore, prove a useful
      alternative to standard combination therapy for the empirical treatment of intra
      abdominal infections.

PMID- 8543494
TI  - Extended-spectrum plasmid-mediated beta-lactamases.
AB  - Extended-spectrum beta-lactamases (ESBLs) are mutant enzymes which derive from
      TEM or SHV (class A) enzymes. They confer variable levels of resistance to
      cefotaxime, ceftazidime and other broad-spectrum cephalosporins and to
      monobactams such as aztreonam but have no detectable activity against cephamycins
      and carbapenems. Recently, new plasmid-mediated ESBLs, not derived from TEM or
      SHV enzymes but related to cephalosporinases of Enterobacteriaceae (class C
      enzymes), that confer resistance to all cephalosporins including cephamycins,
      have been reported. However, to date there have been no reported outbreaks due to
      strains producing transferable cephalosporinases. Klebsiella pneumoniae is the
      species in which the ESBL enzymes have been most commonly reported around the
      world. Most of the clinical isolates that produce TEM- or SHV-derived ESBL, come
      from hospitalised patients and have frequently caused nosocomial outbreaks. Care
      should be taken in the selection of a beta-lactam for the treatment of infections
      because the presence of an ESBL does not prevent other mechanisms of resistance,
      such as decreased permeability, from emerging. Broad-spectrum cephalosporins
      including cefepime and cefpirome are hydrolysed by ESBL. However, low level
      resistance to cefotaxime, ceftriaxone, cefepime and aztreonam does occur in some
      strains producing certain TEM-derived ESBL. It remains to be seen, therefore,
      whether such isolates are clinically susceptible to these drugs. The combination
      of a third-generation cephalosporin and a beta-lactamase inhibitor such as
      sulbactam could be of interest against some strains producing certain ESBLs.
      Among the 7-alpha-methoxy cephalosporins, cefotetan and latamoxef are the most
      active. However, cephamycins should be used with caution to treat infections
      caused by ESBL-producing K. pneumoniae because of the relative ease with which
      clinical strains decrease the expression of outer membrane proteins. The most
      active beta-lactams are the carbapenems, imipenem and meropenem, which are highly
      resistant to hydrolysis by TEM and SHV related beta-lactamases. Meropenem is
      intrinsically the more active agent, with MICs (0.03-0.12 mg/L) generally lower
      than those of imipenem (0.06-0.5 mg/L) and appears stable to all the beta
      lactamases belonging to class A or C, including those with an extended-spectrum
      against third-generation cephalosporins.

PMID- 8543495
TI  - Meropenem versus imipenem/cilastatin in intra-abdominal infections requiring
      surgery. Meropenem Study Group.
AB  - In a multicentre, open, randomised study, the efficacy and tolerability of
      intravenous meropenem (1 g every 8 h, infusion or bolus) was compared with that
      of intravenous imipenem/cilastatin (1 g every 8 h, infusion) in 232 hospitalised
      patients with moderate to severe intra-abdominal infections. At the end of
      therapy, a satisfactory clinical response (cure or improvement) was seen in 79/82
      (96%) evaluable meropenem patients and 83/88 (94%) imipenem/cilastatin patients;
      this was still seen at follow-up (57/63; 90% and 58/66; 88%, respectively). A
      satisfactory bacteriological response (elimination or presumed elimination) was
      seen in 69/82 (84%) meropenem patients and 71/88 (81%) imipenem/cilastatin
      patients at the end of therapy and in 52/62 (84%) and 55/70 (79%), respectively,
      at follow-up. There was a high level of clinical cure or improvement (95% for
      both treatment groups) in the 120 patients (60 in each group) who had
      polymicrobial infections. A similar incidence of adverse events was seen in each
      group: 45/116 patients in the meropenem group (72 events) and 42/116 patients in
      the imipenem/cilastatin group (65 events); the adverse event profiles were also
      similar, with injection site inflammation and elevated transaminases the most
      frequent in both groups. The results of this study indicate that monotherapy with
      meropenem was as effective and as well tolerated as the combination of
      imipenem/cilastatin in the treatment of moderate to severe intra-abdominal
      infections.

PMID- 8543496
TI  - Safety profile of meropenem: international clinical experience based on the first
      3125 patients treated with meropenem.
AB  - Data from 3125 patients (3220 patient exposures) treated with meropenem were
      compared with those from 2886 patients (2960 patient exposures) treated with a
      variety of comparator agents including cephalosporins (alone or in combination
      with aminoglycosides or an anti-anaerobe agent) and imipenem/cilastatin. Patients
      treated included those with bacterial infections of the lower respiratory tract,
      urinary tract and skin and soft tissues, abdominal, obstetric and gynaecological
      infections, meningitis, febrile episodes in neutropenic patients and paediatric
      patients with infections. In three studies, meropenem was administered
      intramuscularly; in the remainder, meropenem was given by 15-30 min iv infusion
      or by bolus injection over approximately 5 min. The usual dosages were 500 mg or
      1 g 8 hourly in adults and 10 or 20 mg/kg 8 hourly in children. In bacterial
      meningitis, the meropenem dosage in adults was 2 g 8 hourly and 40 mg/kg 8 hourly
      in children. The overall pattern and frequency of adverse events with meropenem
      were similar to those of the other beta-lactam antibiotics with which it was
      compared. The most frequently reported adverse events were diarrhoea, rash,
      nausea and vomiting, thrombocytosis, eosinophilia and changes in hepatic
      biochemistry. Abnormal laboratory tests occurred with similar frequencies between
      meropenem and the comparator agents. The safety profile of meropenem was similar
      in adults and children, and the presence of renal impairment did not alter the
      safety profile of meropenem. Experience in clinical studies in 3220 patient
      exposures has revealed no unusual or unexpected toxicity. The possibility of
      administration by either iv infusion or bolus injection with a low incidence of
      nausea and vomiting also provides flexibility in the clinical management of
      patients. Moreover, the low incidence of reported seizures and good tolerability
      at high doses, make meropenem particularly useful for the treatment of meningitis
      and other indications which carry a risk of seizures, or in the treatment of
      serious infections where high doses of antibiotics are frequently indicated.

PMID- 8543497
TI  - A comparison of the pharmacokinetics of meropenem after administration by
      intravenous injection over 5 min and intravenous infusion over 30 min.
AB  - The pharmacokinetics of meropenem were determined in healthy volunteers after
      intravenous injection over 5 min or iv infusion over 30 min. Five volunteers
      received meropenem 500 mg and six volunteers received 1000 mg. For both doses,
      administration over 5 rather than 30 min doubled the plasma concentrations
      observed at the end of the dosing period. Comparison of the other data derived
      from the two modes of administration indicated that rapid administration of
      meropenem did not appreciably alter its disposition pharmacokinetics. Plasma
      clearance, renal clearance, non-renal clearance, terminal half-life and volume of
      distribution were unchanged. Within 1 h of dosing, the plasma concentrations were
      very similar indicating that dosing over either time period would result in
      similar antimicrobial cover and thus should not affect efficacy. There were no
      changes in tolerability of meropenem associated with more rapid administration.

PMID- 8543498
TI  - A compilation of meropenem tissue distribution data.
AB  - Meropenem body fluid and tissue concentration data from both published studies
      and samples obtained during efficacy evaluation have been compiled and presented
      according to a consistent format to facilitate comparison. The concentration data
      have been compared with the mode MIC data available for the pathogens isolated
      during the clinical evaluation of meropenem. These data support the widespread
      and rapid penetration of meropenem into the interstitial fluid of those tissues
      not protected by a tight epithelial barrier. Furthermore, they suggest that the
      proposed dosages of meropenem 500 mg or 1 g tds would provide an adequate
      duration of cover at tissue sites for the treatment of a range of commonly
      occurring pathogens. A higher dosage of 40 mg/kg or 2 g in adults given tds would
      be recommended for meningitis based on the penetration of meropenem into CSF.
      Overall, the tissue and body fluid data presented confirm the expectation, based
      on the plasma concentrations and theoretical arguments, that meropenem is rapidly
      and readily distributed into the interstitial fluid, thereby producing
      concentrations in tissues likely to be clinically effective. This is consistent
      with the available clinical data on the therapeutic efficacy of meropenem.

PMID- 8543499
TI  - Penetration of meropenem into heart valve tissue.
AB  - Thirty-three patients requiring cardiac valve surgery were administered meropenem
      1000 mg by a 5 to 10 min iv injection. Samples of blood, cardiac valve and atrial
      muscle tissue were removed at valvectomy and analysed for meropenem by high
      performance liquid chromatography (HPLC) with UV detection. The plasma
      concentrations observed in the samples from these patients were higher than those
      reported when meropenem 1000 mg was administered to healthy volunteers by 5 min
      iv injection. No clinical adverse events attributable to meropenem were reported
      and the single 1000 mg dose was well tolerated. The penetration of meropenem into
      cardiac muscle and valve tissue was rapid and in excess of that expected solely
      on the basis of distribution into extracellular fluid. The concentrations
      achieved in the tissues were in excess of the MICs of the pathogens commonly
      causing endocarditis.

PMID- 8543500
TI  - The pharmacokinetics of meropenem in infants and children: a population analysis.
AB  - Plasma meropenem concentration versus time data collected during a single dose,
      pharmacokinetic study in infants and children were analysed using the population
      pharmacokinetics program NONMEM. A total of 300 meropenem concentrations was
      obtained from 65 patients ranging from 2 months to 12 years of age; weighing
      between 3.7 and 46 kg. A two-compartment open pharmacokinetic model with a zero
      order infusion over 30 min was fitted to the data. The most important determinant
      of meropenem clearance was the creatinine clearance but an additional improvement
      occurred when a nonlinear dependence upon age was included. The most important
      determinant of the volume of distribution in the central and peripheral
      compartments was the body weight. The distributional clearance showed a nonlinear
      dependence on body weight. Demographic factors other than weight and age were not
      found to be influential in the model. Both clearance and distributional clearance
      were markedly different in the younger (< 2 years) or lighter (< 10 kg) patients,
      respectively. Thereafter the parameter values slowly approached those found in
      adults. In this study, a mean of 4.6 samples per patient was used to provide
      information on the pharmacokinetics and the determinants of the pharmacokinetic
      variability in infants and children. The findings in the younger, lighter
      patients, if generally applicable, might have significance for the dosage
      recommendations for drugs with narrow therapeutic indices.

PMID- 8543501
TI  - Efficacy of meropenem in experimental meningitis.
AB  - Meropenem and comparator antibiotics, including ceftriaxone, ceftazidime, benzyl
      penicillin and a combination of ampicillin plus gentamicin, were evaluated in a
      model of bacterial meningitis in the guinea-pig. The model is an acute infection
      in which challenge with each organism, if untreated, causes an increase in
      numbers of white blood cells, elevation of protein concentrations and 6-8 log10
      cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influenzae,
      Neisseria meningitidis, three strains of Streptococcus pneumoniae (two penicillin
      resistant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes
      all responded to meropenem, which was as active as the comparator agents in all
      studies, and was more active in most. Of particular note were the results seen
      against S. pneumoniae (penicillin-resistant) infections, in which meropenem was
      significantly more effective than ceftriaxone. Also notable were results from the
      P. aeruginosa infection where meropenem, at low doses, was more effective than
      ceftazidime. Activity against L. monocytogenes was equivalent to that produced by
      treatment with the combination of ampicillin plus gentamicin, even when treatment
      was delayed. These results show that, in an animal model, meropenem penetrates
      into CSF in concentrations sufficient to produce significant reductions in the
      numbers of common and less common pathogens.

PMID- 8543502
TI  - A randomised comparison of meropenem with cefotaxime or ceftriaxone for the
      treatment of bacterial meningitis in adults. Meropenem Meningitis Study Group.
AB  - Third-generation cephalosporins are presently the agents of choice for the
      empirical antimicrobial therapy of bacterial meningitis. However, a number of
      factors associated with these agents, namely the development of resistance by
      pneumococci, limited activity against some Enterobacteriaceae and Pseudomonas
      spp., and the possible adverse effects of their bacteriolytic mode of action,
      indicate that newer classes of antimicrobial agents be evaluated for the
      treatment of bacterial meningitis. Meropenem is a carbapenem antibiotic which is
      highly active against the major bacterial pathogens causing meningitis, and
      penetrates well into the cerebrospinal fluid. Two prospective randomised studies
      in 56 adult bacterial meningitis patients have compared meropenem 40 mg/kg 8
      hourly, up to a maximum of 6 g/day (n = 28) with cephalosporin treatment, i.e.
      cefotaxime (n = 17) or ceftriaxone (n = 11). Patients were assessed by
      neurological examination, Glasgow Coma Score and Herson-Todd score. Clinical cure
      was observed in all 23 evaluable patients treated with meropenem (100%) and with
      17 of the 22 evaluable cephalosporin-treated patients (77%). All pre-treatment
      isolates were eradicated except one isolate of Staphylococcus aureus in a
      cefotaxime-treated patient. Neurological sequelae were noted in three meropenem
      and four cephalosporin-treated patients. No patients in either treatment group
      experienced seizures after the start of therapy. This was despite the fact that a
      patient in each group had experienced seizures before therapy, several had
      underlying CNS disorders, and that doses of 6 g/day of meropenem were given.
      Hearing impairment was recorded in 11 meropenem and nine cephalosporin treated
      patients. Three patients in the meropenem group and one in the cephalosporin
      group died during treatment for reasons unrelated to study therapy. Overall, the
      results of this study indicate that meropenem is an effective and well-tolerated
      antibiotic for the treatment of bacterial meningitis in adults.

PMID- 8543503
TI  - Safety and efficacy of meropenem in hospitalised children: randomised comparison
      with cefotaxime, alone and combined with metronidazole or amikacin. Meropenem
      Paediatric Study Group.
AB  - In this multicentre, randomised study of 170 children hospitalised with bacterial
      infections, meropenem (10 to 20 mg/kg every 8 h) was found to be as effective and
      as well tolerated as cefotaxime (100 to 150 mg/kg/day), with or without amikacin
      or metronidazole. Most drug-related adverse events were mild and self-limiting.
      Neither regimen was associated with seizures. The overall incidence of clinically
      significant laboratory changes was similar in the two treatment groups.
      Satisfactory clinical responses were obtained in 94/96 (98%) patients treated
      with meropenem monotherapy and 43/46 (93%) children treated with cefotaxime
      regimens, while satisfactory bacteriological responses were obtained in 25/28
      (89%) and 9/10 (90%) patients, respectively. Meropenem monotherapy appears to be
      a well-tolerated and effective drug for paediatric infections.

PMID- 8543504
TI  - More on stress-resilient children.

PMID- 8543505
TI  - Encopresis [corrected] secondary to sexual assault.

PMID- 8543506
TI  - Sertraline for body dysmorphic disorder.

PMID- 8543507
TI  - Carbamazepine hypersensitivity.

PMID- 8543508
TI  - Research on the treatment of sexually abused children: a review and
      recommendations.
AB  - OBJECTIVE: To review findings and conclusions from 29 studies that evaluated with
      quantitative outcome measures the effectiveness of treatments for sexually abused
      children. RESULTS: The studies overall document improvements in sexually abused
      children consistent with the belief that therapy facilitates recovery, but only
      five of them marshal evidence that the recovery is not simply due to the passage
      of time or some factor outside therapy. There has yet to be a true large-scale,
      randomized trial of treatment versus control. The studies suggest that certain
      problems, such as aggressiveness and sexualized behavior, are particularly
      resistant to change and that some children do not improve. A number of
      considerations that merit special attention in future sexual abuse therapy
      outcome research are identified, including (1) the diversity of sexually abused
      children, (2) the problem of children with no symptoms, (3) the possible
      existence of serious "sleeper" effects, (4) the importance of family context on
      recovery, (5) the utility of abuse-focused therapy and targeted interventions,
      (6) the optimal length of treatment, (7) the problem of treatment dropouts, and
      (8) the development and use of abuse-specific outcome measures. CONCLUSIONS: The
      need for more treatment outcome research is highlighted by the rising demand for
      accountability in the health care system that will increasingly require
      professionals in the field of sexual abuse treatment to justify their efforts and
      their methods.

PMID- 8543509
TI  - Obsessive-compulsive disorder in a birth cohort of 18-year-olds: prevalence and
      predictors.
AB  - OBJECTIVE: To report descriptive epidemiological information on obsessive
      compulsive disorder (OCD) in an unselected birth cohort of 930 males and females,
      aged 18 years. METHOD: An epidermiological study of the prevalence of self
      reported OCD at age 18, and a longitudinal analysis of the prospective predictors
      of OCD. RESULTS: Using the Diagnostic Interview Schedule, the authors found a 1
      year prevalence rate of 4%, with a male-female ratio of 0.7:1. The majority of
      OCD cases met criteria for a comorbid disorder, most commonly depression (62%),
      social phobia (38%), and substance dependence (alcohol 24%, marijuana 19%).
      CONCLUSIONS: Data collected on the sample from birth to age 18 years indicated
      that many childhood risk factors theorized in the literature did not predict OCD
      in this sample. However, a history of depression and substance use were
      prospective risk factors for OCD.

PMID- 8543510
TI  - Course of obsessive-compulsive disorder in children and adolescents: a
      prospective follow-up study of 23 Danish cases.
AB  - OBJECTIVE: The course of obsessive-compulsive disorder (OCD) in childhood and
      adolescence was analyzed. METHOD: Twenty-three (88%) of 26 children and
      adolescents with OCD, all referred to a county child psychiatric clinic as
      inpatients or outpatients, were longitudinally evaluated every 6 months for
      obsessive-compulsive symptomatology. At follow-up, 1 1/2 to 5 years after
      referral (mean follow-up time 3.2 years, SD 1.1), obsessive-compulsive as well as
      comorbid symptomatology was assessed and compared with that of an age- and sex
      matched child psychiatric control group. RESULTS: Approximately one half of the
      children and adolescents retained an OCD diagnosis at follow-up. One third of
      these had an episodic course of the illness, and two thirds had chronic OCD. None
      in the control group had clinical OCD at follow-up, but three had subclinical
      obsessive-compulsive symptoms. Thirteen of the probands with OCD received
      medication (either clomipramine or citalopram) for a period of 1/2 to 2 years
      (mean 1.4 years). Medication seemed to reduce the severity of OCD in most cases.
      CONCLUSIONS: This short-term but intensive study supported theories of OCD as an
      illness with fluctuating severity. Previous findings, that OCD seems to be
      chronic in approximately half of the cases, were supported by this study.

PMID- 8543511
TI  - Long-term course of obsessive-compulsive disorder treated in adolescence.
AB  - OBJECTIVE: To investigate the long-term course of obsessive-compulsive disorder
      treated in adolescence. METHOD: Fifteen young adults treated for the disorder in
      adolescence, mainly through not only by behavior therapy and family therapy, were
      followed up between 9 and 14 years later. RESULTS: Data were collected on 14 of
      the cases (93%, N = 15) from various sources including interview in person in 6
      cases. Of the 14 cases, 6 were found to satisfy DSM-III-R criteria for obsessive
      compulsive disorder at long-term follow-up, while 8 were not. These recovered
      participants were not currently taking medication, and long-lasting recovery was
      associated with good social adjustment. Chronic course was not attributable to
      lack of subsequent treatment. CONCLUSIONS: The recovery rate of 57% (N = 14) is
      similar to those found in other recent studies of outcome following vigorous
      treatment in adolescence. The findings are over the longest follow-up period so
      far reported for obsessive-compulsive disorder treated in adolescence. Positive
      response to treatment in adolescence can be followed by relapse after longer
      periods than have usually been studied.

PMID- 8543512
TI  - Childhood trichotillomania: clinical phenomenology, comorbidity, and family
      genetics.
AB  - OBJECTIVE: DSM-IV defines trichotillomania as an impulse disorder with rising
      tension followed by relief or gratification. Alternative formulations view
      trichotillomania as an internalizing disorder or variant of obsessive-compulsive
      disorder (OCD). This study addresses this controversy by examining the
      phenomenology, comorbidity, and family genetics of childhood trichotillomania.
      METHOD: Fifteen chronic hair-pullers (13 girls), aged 9 through 17 years (mean
      12.3 +/- 2.3 years), were systematically assessed. Child Behavior Checklist
      (CBCL) profiles of the hair-pulling girls were compared with those of 37 girls
      from a general child psychiatry clinic and of 15 girls with OCD. RESULTS: All the
      hair-pullers had impairing cosmetic disfigurement; however, 4 subjects (26.7%)
      denied rising tension or relief. All three groups had comparable global CBCL
      problem scores. The CBCL symptom profile of the hair-pulling group differed
      significantly from that of the general clinic group but strongly resembled that
      of the OCD group. The hair-pulling group, however, had few obsessions or
      compulsions aside from hair-pulling; two (13%) subjects met criteria for OCD. As
      a group, hair-pulling subjects had substantial comorbid psychopathology, and a
      parental history of tics, habits, or obsessive-compulsive symptoms was common.
      CONCLUSIONS: These findings lend only partial support to the notion of
      trichotillomania as an OCD-spectrum disorder. Rising tension followed by relief
      or gratification may not be an appropriate diagnostic criterion for
      trichotillomania.

PMID- 8543513
TI  - Electrocardiographic changes during desipramine and clomipramine treatment in
      children and adolescents.
AB  - OBJECTIVE: With the increased use of tricyclic antidepressants in children, and
      several reports of several sudden deaths associated with desipramine (DMI)
      treatment, systematic study of their cardiac effects is indicated. In the present
      study, DMI's and clomipramine's (CMI) short-term effects on the electrocardiogram
      (ECG) were compared, as well as the long-term effects of CMI. METHOD: The ECGs of
      47 children and adolescents in treatment trials were examined at baseline, after
      5 weeks of CMI and of DMI treatment, and during CMI maintenance (mean duration
      24.6 months). RESULTS: At 5 weeks of CMI and of DMI treatment, the heart rate,
      PR, QRS, and QT-corrected (QTc) intervals on ECG were significantly increased
      from baseline (p < .05); DMI increased PR and QRS intervals more than CMI (p <
      .05), and CMI increased QTc more (p < .05). Tachycardia was the most common
      change (36%). More patients experienced an incomplete intraventricular conduction
      delay during DMI treatment (23%, 9/39) than during CMI (2%, 1/47) (p < .05). Four
      patients (9%) acutely developed a prolonged QTc during either DMI or CMI. Long
      term maintenance ECGs during CMI treatment (n = 25) were not significantly
      different from that at week 5, although some individuals developed or resolved
      specific ECG changes. CONCLUSION: CMI and DMI both produced ECG changes typically
      reported for tricyclic antidepressants, and they differed on specific ECG
      changes. Changes in ECG measures for individuals from short to long term suggest
      that continued monitoring is required.

PMID- 8543514
TI  - Case study: emergence of transient compulsive symptoms during treatment with
      clothiapine.
AB  - Serotonergic dysregulation in obsessive-compulsive disorder has been repeatedly
      demonstrated. Recent reports on the emergence of obsessive-compulsive symptoms in
      patients treated with clozapine support a hyposerotonergic hypothesis of
      obsessive-compulsive disorder. The authors report the emergence of de novo
      compulsive symptoms in a drug-naive 8-year-old schizophrenic child, shortly after
      the initiation of treatment with clothiapine. Clothiapine, an atypical
      antipsychotic agent, shares with clozapine its strong antiserotonergic
      properties. It seems that antagonistic activity of atypical neuroleptics at
      postsynaptic serotonergic receptors might be responsible for the development of
      iatrogenic obsessive-compulsive symptoms.

PMID- 8543515
TI  - Changes in daily mood and self-restraint among undercontrolled preadolescents: a
      time-series analysis of "acting out".
AB  - OBJECTIVE: Acting out among boys with disruptive behavior disorders was
      investigated by evaluating how changes in their daily moods predicted changes in
      their behavior. METHOD: During a 6-week period, 20 preadolescent boys enrolled in
      day treatment programs rated their mood upon arrival at school, and teachers
      rated their behavior at the end of the day. Time-series and path-analytic
      methodologies were used to analyze the data. RESULTS: The boys did engage in
      emotional acting out, in that their morning moods predicted their subsequent
      disruptive behavior, controlling for both individual differences and their
      behavior the previous day. Boys' mood changes served as a mediator between the
      intensity of interpersonal conflicts in their lives (with peers and among
      significant adults) and decrements in their self-restraint. Acting-out behavior
      was associated with defensive processes, in that boys who reported low subjective
      distress and whom the teachers rated as high in denial of distress had the
      strongest links between their moods and behavior. Individual differences in
      levels of conduct problems, but not hyperactivity, also predicted acting out.
      CONCLUSION: Emotional processes and defensive acting out may often be integral
      aspects of conduct-disordered behavior.

PMID- 8543516
TI  - Psychopathology, biopsychosocial factors, crime characteristics, and
      classification of 25 homicidal youths.
AB  - OBJECTIVE: This study investigates diagnostic, behavioral, offense, and
      classification characteristics of juvenile murderers. METHOD: Twenty-five
      homicidal children and adolescents were assessed using the Diagnostic Interview
      for Children and Adolescents, clinical interviews, record review, and all
      available collateral data. RESULTS: DSM-III-R psychopathology was found in 96% of
      these youths, and one half of them had experienced suicidal ideation at some
      point in their lives. Nevertheless, only 17% had ever received mental health
      treatment. Family and school dysfunction were present in virtually all subjects.
      Histories of abuse, prior violence, arrests, and promiscuous sexual behavior were
      typical. Motives were equally divided between crime-based and conflict-based
      causes. A weapon was used in 96% of cases. Significant differences were found
      between crime classification groups and victim age, physical abuse, IQ, and
      victim relationship. In addition, those who committed sexual homicide were
      significantly more likely to have engaged in overkill, used a knife, and been
      armed beforehand. Ten profile characteristics present in at least 70% of these
      juveniles were identified. All murders were readily classified according to the
      FBI Crime Classification Manual (CCM). CONCLUSIONS: These findings support
      juvenile murderers as being an inadequately treated, emotionally and behaviorally
      disturbed population with profound social problems. The CCM proved to be a useful
      instrument for the classification of this sample.

PMID- 8543517
TI  - Case study: neuroleptic withdrawal dyskinesia exacerbated by ongoing stimulant
      treatment.
AB  - Risk factors for neuroleptic withdrawal dyskinesia in children have not been well
      studied. The authors present a case of a child who had been treated with a
      combination of neuroleptics and stimulants for nonpsychotic aggressive behavior.
      A severe withdrawal dyskinesia precipitated by neuroleptic tapering was
      ameliorated by discontinuation of the psycho-stimulant. Although stimulants have
      been reported to increase certain involuntary movement disorders, this is the
      first known report of psychostimulant exacerbation of withdrawal dyskinesia.

PMID- 8543518
TI  - Impact of adversity on functioning and comorbidity in children with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: Prior research on risk factors for attention-deficit hyperactivity
      disorder (ADHD) has shown that familial risk factors play a role in the
      disorder's etiology. This study investigated whether features of the family
      environment were associated with ADHD. METHOD: One hundred forty children with
      ADHD and 120 normal control probands were studied. Subjects were Caucasian, non
      Hispanic males between the ages of 6 and 17 years. Exposure to parental
      psychopathology and exposure to parental conflict were used as indicators of
      adversity, and their impact on ADHD and ADHD-related psychopathology and
      dysfunction in children was assessed. RESULTS: Increased levels of environmental
      adversity were found among ADHD compared with control probands. The analyses
      showed significant associations between the index of parental conflict and
      several of the measures of psychopathology and psychosocial functioning in the
      children. In contrast, the index of exposure to parental psychopathology had a
      much narrower impact, affecting primarily the child's use of leisure time and
      externalizing symptoms. CONCLUSIONS: A relationship appears to exist between
      adversity indicators and the risk for ADHD as well as for its associated
      impairments in multiple domains. These findings confirm previous work and stress
      the importance of adverse family-environment variables as risk factors for
      children who have ADHD.

PMID- 8543519
TI  - Pemoline effects on children with ADHD: a time-response by dose-response analysis
      on classroom measures.
AB  - OBJECTIVE: To evaluate the dose-response by time-response characteristics of
      pemoline (Cylert) on dependent measures of behavior and academic performance in a
      laboratory classroom. METHOD: After a 2-week baseline, a double-blind crossover
      design was used to compare placebo, 18.75 mg, 37.5 mg, 75 mg, and 112.5 mg of
      pemoline, q.a.m., with each dose administered for 1 week. Medication was given at
      9:00 A.M., and performance was measured beginning immediately and beginning 2, 4,
      and 6 hours after ingestion. The dependent measures included number of math
      problems completed correctly, teacher-recorded rates of on-task behavior and
      noncompliance, and teacher ratings on an Abbreviated Conners Teacher Rating
      Scale. RESULTS: There were linear effects of medication, with pemoline doses
      greater than 18.75 mg having an effect beginning 2 hours after ingestion and
      lasting through the seventh hour after ingestion. CONCLUSIONS: Results are
      contrasted with widespread misbeliefs regarding pemoline's time course and
      efficacy.

PMID- 8543520
TI  - Prevalence of mental disorder in military children and adolescents: findings from
      a two-stage community survey.
AB  - OBJECTIVE: Because previous reports have suggested that children of military
      families are at greater risk for psychopathology, this study examines the levels
      of psychopathology in an epidemiological community sample of military children
      all living on a military post. METHOD: Standardized psychopathology rating scales
      and a structured diagnostic interview (the Diagnostic Interview Schedule for
      Children [DISC], version 2.1) were used in a multimethod, multistage survey; 294
      six- to seventeen-year-old military children and their parents participated in
      the study. RESULTS: Parent- and child-administered structured DSM-III-R DISC
      interviews indicated that children's levels of psychopathology were at levels
      consistent with studies of other normal samples. In addition, parents' and
      children's symptom checklist ratings of children were at national norms, as were
      parents' ratings of their own symptoms. CONCLUSIONS: Overall results do not
      support the notion that levels of psychopathology are greatly increased in
      military children. Further studies of military families should address the
      effects of rank and socioeconomic status, housing, and the current impact of life
      stressors on the parents as well as the children, in order to avoid drawing
      erroneous conclusions about parts or all of the military community.

PMID- 8543521
TI  - Continuity of psychopathology in a community sample of adolescents.
AB  - OBJECTIVE: To examine the continuity between the primary (first) diagnosis and
      secondary (second) diagnosis of those adolescents who have more than one episode
      of psychiatric disorder. Data were examined to determine whether the second
      episode "breeds true" (i.e., remains within the same diagnostic category as the
      first) or involves a different disorder. METHOD: The sample consisted of 236
      youngsters selected from the larger (n = 1,507) population of adolescents (aged
      14 through 18 years) from the Oregon Adolescent Depression Project who had been
      assessed on two occasions, approximately 1 year apart. RESULTS: Results support
      the continuity hypothesis for the categories of disorder studied (major
      depression, anxiety, disruptive, substance use), with the exception of dysthymia.
      Primary dysthymia did not result in the diagnosis of secondary dysthymia, because
      most adolescents who had dysthymia had not recovered within the time frame of the
      study and were chronic cases, often with secondary anxiety. Also presented are
      data on age of onset of disorder (lowest for anxiety and highest for substance
      use) and information on remission intervals between episodes (well time) (lowest
      for substance use and highest for anxiety). CONCLUSIONS: The findings are
      interpreted as providing support for the "breed true" hypothesis, although
      clearly not all second episodes are identical with the first. While the
      psychosocial factors examined did not predict the nature of the second disorder,
      this clearly needs further study.

PMID- 8543522
TI  - Race and gender differences in the treatment of psychiatric disorders in young
      adolescents.
AB  - OBJECTIVE: Most children and adolescents with mental illness remain untreated.
      Evidence suggests that race is a factor in the referral of children for
      treatment. This study examines race and gender differences in treatment of
      adolescent psychiatric disorders. METHOD: During a two-stage, school-based,
      epidemiological study of depression, data were collected on 478 adolescents.
      Instruments included the Schedule for Affective Disorders and Schizophrenia for
      School-Age Children and the Children's Global Assessment Scale. RESULTS: Twenty
      two percent of the sample had contact with professionals during the prior year,
      including 56% of adolescents with a psychiatric diagnosis. Significant odds
      ratios (ORs) were found between all diagnoses and treatment. Trends for
      undertreatment of females and African-Americans were evident in univariable and
      multivariable models. The OR (0.34) for African-American females was significant
      in the multivariable model. African-Americans were significantly more likely to
      receive only one or two treatment contacts. CONCLUSION: Data suggest race and
      gender differences in the treatment of adolescent psychiatric disorders. Possible
      explanations include referral bias, low cultural competence of mental health
      professionals, and cultural differences in the expression and tolerance of
      symptoms and help-seeking behaviors. Further study of factors influencing
      treatment decisions is needed.

PMID- 8543523
TI  - The cyclic dilemma: organic, functional, and environmental interaction in a young
      teenager.
AB  - This Grand Rounds considers an early-adolescent female who demonstrated a mixed
      clinical picture including rapid cycling of psychotic behavior. The case presents
      issues commonly faced in hospital practice and provides an example of the use of
      standardized instruments in assessment and monitoring treatment, as well as a
      discussion of issues germane to inpatient child and adolescent psychiatrists and
      related treatment team members.

PMID- 8543524
TI  - Sleep-wake schedule disorders.

PMID- 8543525
TI  - Clinical perspectives: combined pharmacotherapy.

PMID- 8543526
TI  - Clinical perspectives: combined pharmacotherapy.

PMID- 8543527
TI  - Neuroimaging in child and adolescent neuropsychiatric disorders.
AB  - OBJECTIVE: To review the major findings and pathophysiological implications of
      imaging studies of neuropsychiatric disorders that onset in childhood or
      adolescence. METHOD: More than 200 neuroimaging studies were selected for review
      from Medline searches if the studies concerned developmental neuropsychiatric
      disorders such as autism, fragile X syndrome, Down syndrome, schizophrenia,
      obsessive-compulsive disorder, Tourette's syndrome, attention-deficit
      hyperactivity disorder, and dyslexia. RESULTS: Disordered central nervous system
      development may produce evidence of cortical neuronal migration abnormalities in
      autism, smaller cortical structures in Down syndrome, frontal lobe deficits and
      larger basal ganglia in schizophrenia, hypoplastic basal ganglia in Tourette's
      syndrome, aberrancies of the planum temporale in dyslexia, and hypoplastic
      cerebellar structures in numerous developmental disorders. Normal cerebral
      asymmetries appear to be disrupted in a number of disorders, including
      schizophrenia, Tourette's syndrome, attention deficit disorder, and dyslexia.
      CONCLUSIONS: Neuroimaging data regarding pathological central nervous system
      development in childhood are still sparse, and many of the findings in
      developmental disorders of childhood onset concern the study of adult subjects
      with those disorders. Nevertheless, imaging modalities previously used only in
      adults are with increasing frequency being applied to the study of children,
      which will likely continue to contribute to the understanding of pathological
      brain structure and function throughout childhood and to the improved treatment
      of these disorders.

PMID- 8543528
TI  - A pilot family study of childhood-onset mania.
AB  - OBJECTIVE: To investigate the familial association of attention-deficit
      hyperactivity disorder (ADHD) and bipolar disorder (BPD) among the first-degree
      relatives of children with comorbid ADHD and BPD. BACKGROUND: In contrast to a
      growing body of literature on childhood non-bipolar depression, little is known
      about childhood BPD. Among the explanations accounting for the lack of
      recognition and identification of these children is the symptomatic overlap of
      BPD with ADHD. Family-genetic studies provide information external to the
      clinical picture and thus are uniquely suited to clarify such issues of
      diagnostic comorbidity. METHOD: Structured diagnostic interviews were used to
      obtain DSM-III-R psychiatric diagnoses on first-degree relatives (n = 46) of
      referred children (aged < or = 12 years) satisfying diagnostic criteria for mania
      using the Schedule for Affective Disorders and Schizophrenia for School-Age
      Children-Epidemiologic Version (n = 16). For comparison, diagnostic information
      on the first-degree relatives of non-bipolar ADHD children and control children
      was examined. RESULTS: The results show high rates of comorbidity between BPD and
      ADHD in children and high rates of both BPD and ADHD in the first-degree
      relatives of these children. Moreover, ADHD and BPD cosegregated among the
      relatives of children with BPD. CONCLUSIONS: These findings, which are consistent
      with the authors' prior study of children with ADHD, provide family-genetic
      evidence for the validity of BPD and ADHD when they exist comorbidly in children.
      Moreover, they suggest that the comorbid condition of ADHD+BPD may be a distinct
      nosological entity.

PMID- 8543529
TI  - Untoward effects of lithium treatment in children aged four through six years.
AB  - OBJECTIVE: To explore the relationship between lithium dose and serum lithium
      level on the occurrence of untoward or toxic effects of lithium in the treatment
      of 20 hospitalized aggressive and/or mood-disordered children aged 4 through 6
      years. METHOD: Clinical and research records of 20 children treated with lithium
      according to an established inpatient protocol were reviewed. Side effects as
      reported by psychiatric staff were categorized by organ system affected and
      severity. RESULTS: During the initial 2 weeks of lithium treatment, 60% of the
      children manifested one or more types of side effects, most commonly central
      nervous system effects. Side effects were seen at doses of 25.6 to 52.1 mg/kg per
      day and at serum levels from 0.65 to 1.37 mEq/L. In general, adverse effects were
      associated with higher lithium doses and lithium levels and were most common
      during the first week of treatment. A potential interaction between concurrent
      infection and more severe side effects was seen. CONCLUSIONS: Side effects occur
      frequently in children aged 6 years and younger during the initiation phase of
      lithium treatment; are related to higher milligram per kilogram doses, higher
      serum lithium levels, and phase of treatment; and may be related to concurrent
      medical illness.

PMID- 8543530
TI  - Case study: mania associated with multiple sclerosis.
AB  - Mania occurs sometimes in association with an organic condition affecting the
      brain. A case of a 15-year-old girl with secondary mania related to multiple
      sclerosis is described, along with a selective review of the subject. The English
      language literature published from 1986 to 1994 was reviewed, but geriatric and
      mentally retarded cases were excluded. This case points out that organic causes,
      often multifactorial, have to be kept in mind when treating patients who have
      mania.

PMID- 8543531
TI  - A case-control family history study of depression in adolescents.
AB  - OBJECTIVE: To examine whether depression aggregates in the families of depressed
      adolescents and to determine whether clinical features and/or comorbid syndromes
      in the depressed adolescents change the risk of psychopathology in relatives.
      METHOD: Lifetime prevalence rates of psychopathology in the first-degree (n =
      228) and second-degree (n = 736) relatives of 76 adolescents with major
      depressive disorder (MDD) and the first-degree (n = 107) and second-degree (n =
      323) relatives of 34 normal control adolescents were assessed by the Family
      History-Research Diagnostic Criteria (FH-RDC) method using the parent/guardian as
      the family informant. RESULTS: Compared with the first-degree relatives of normal
      controls, the relatives of depressed adolescents had significantly higher
      lifetime rates of MDD (25% versus 13%) and "any" of the FH-RDC psychiatric
      disorders (53% versus 36%). The second-degree relatives of adolescents with MDD
      had significantly higher lifetime rates of FH-RDC "other" psychiatric disorder
      (12% versus 7%) and "any" of the FH-RDC psychiatric disorders (22% versus 15%)
      but not MDD (5% versus 6%) compared with the relatives of normal controls. The
      first-degree relatives of depressed adolescents who were also suicidal had
      increased lifetime rates of suicidal behavior which significantly cosegregated
      with MDD. Comorbid conduct disorder in the depressed adolescent was associated
      with increased rates of antisocial personality disorder in the first-degree
      relatives and also tended to cosegregate with MDD. CONCLUSIONS: The current study
      provides further evidence for the familial aggregation of depression in
      adolescent-onset MDD. This study also suggests that the familial aggregation of
      nonaffective psychiatric disorders depends on the clinical features and comorbid
      syndromes present in the depressed adolescent proband.

PMID- 8543532
TI  - Symptoms of DSM-III-R major depression in adolescence: evidence from an
      epidemiological survey.
AB  - OBJECTIVE: To examine the phenomenology of DSM-III-R major depression among
      adolescents diagnosed as "cases" in a community-based epidemiology study. METHOD:
      A representative sample (N = 1,710) of older adolescents from several Oregon
      communities were interviewed using structured diagnostic schedules and DSM-III-R
      criteria in two annual assessments. Although the focus was depression, diagnoses
      were made for most child and adolescent psychiatric disorders. RESULTS: Nearly
      30% of the sample at baseline had at least one current symptom of DSM-III-R major
      depression, but only 2.6% received a diagnosis. The most prevalent symptoms at
      baseline were depressed mood, sleep, and thinking problems. For new, or incident
      cases, the most frequent symptoms involved depressed mood, anhedonia, and
      thinking problems. Among those adolescents who had experienced two episodes of
      major depression, there was low concordance across episodes for both diagnostic
      criteria and specific symptoms. Comparisons with six studies of adolescent
      patients indicate our community "cases" are phenomenologically very similar to
      clinical cases of major depression in treatment settings. CONCLUSIONS: The
      results presented, along with those from other studies of adults and children,
      provide strong evidence that DSM criteria for major depression are appropriate
      for adolescents. That is, DSM-III-R symptom criteria are manifested by both
      youths and adults, although the relative frequency of these criterion symptoms
      appear to be age-related.

PMID- 8543533
TI  - Predicting the one-year course of adolescent major depression.
AB  - OBJECTIVE: To identify specific clinical and social functioning variables that
      predict persistence of major depression over a 1-year period of follow-up.
      METHOD: The sample consisted of 67 adolescents with major depression, drawn from
      consecutive referrals to psychiatric clinics in a defined, geographic catchment
      area. Clinical interviews and questionnaires measuring behaviors, symptoms, and
      social functioning were administered to both the adolescent and a parent at
      inception and at follow-up. Discriminant function analyses were used to identify
      inception variables that predicted clinical course independent of severity of
      depressive symptoms and global functioning. RESULTS: At 1-year follow-up, major
      depression remitted in 66% of subjects. Persisters were characterized at
      inception as older, more likely to have substance use or anxiety disorders, less
      involved with fathers, and less responsive to mother's discipline compared with
      remitters. The effect of these prognostic factors was independent of symptom
      severity and global functioning. CONCLUSION: These variables appear to reflect
      perpetuating and ameliorating factors influencing the short-term course of major
      depression. The findings suggest that treatments for adolescent depression that
      aim to enhance parent-adolescent relationships, and that specifically target
      coexisting disorders, should be evaluated for effectiveness.

PMID- 8543534
TI  - Predicting diabetic control from competence, adherence, adjustment, and
      psychopathology.
AB  - OBJECTIVE: To determine what psychological and behavioral factors were most
      predictive of diabetic control. METHOD: Seventy-nine youths with diabetes were
      assessed cross-sectionally, using youths' reports of self-esteem, anxiety, and
      attitudes about diabetes, and parents' reports of competence and psychopathology
      (from the Child Behavior Checklist) and diabetic adherence as independent
      variables. Glycosylated hemoglobin A1c was the dependent variable, reflecting
      diabetic control. After the effects of several background variables were
      partialed out, a principal-components analysis grouped the substantive variables
      into three larger components. RESULTS: Among the background variables, duration
      of illness and family size significantly predicted diabetic control. Among
      substantive components, Competence/Adherence (including Total Competence, dietary
      compliance, and frequency of blood glucose checks) was highly predictive of
      diabetic control, primarily due to the effect of Total Competence. Adjustment
      (including self-esteem, anxiety levels, and attitudes about diabetes) and
      Psychopathology were less predictive. A model was constructed showing the
      relationships between these predictive components and diabetic control.
      CONCLUSIONS: In this generally well-adjusted sample, that Total Competence, more
      than other measures, predicted diabetic control suggests it could be used by
      clinicians to anticipate diabetic youths at risk.

PMID- 8543535
TI  - Psychosocial adjustment in children with port-wine stains and prominent ears.
AB  - OBJECTIVE: To evaluate psychosocial adjustment in children with port-wine stain
      (PWS) and children with prominent ears (PE). METHOD: Thirty-two children aged 7
      to 16 years with facial PWS and 42 children with PE were evaluated using the
      Harter Self-Perception Profile, the Revised Children's Manifest Anxiety Scale,
      the Children's Depression Inventory, the Disfigurement Perception Scale, and the
      Child Behavior Checklist. Results were compared with normative data for the local
      population or with a control group. Profile scores were correlated with severity
      of the PWS or prominence of the ears. RESULTS: Children with PE had poorer self
      perception, higher concentration anxiety, and more internalizing and
      externalizing symptoms, and they were more withdrawn and had more social problems
      than children with PWS. The children with PWS functioned as well as or better
      than nondisfigured peers on measurements of psychosocial adjustment, while
      children with PE scored lower than nondisfigured peers on measures of self
      perception and parent-rated social and attention problems. There was no
      correlation between degree of disfigurement and level of psychosocial adjustment.
      CONCLUSIONS: Psychosocial adjustment varied according to the nature of the
      disfigurement or deformity and was unrelated to the severity of the
      disfigurement.

PMID- 8543536
TI  - Defense mechanisms in severe adolescent anorexia nervosa.
AB  - OBJECTIVE: To compare ego defense mechanisms in adolescents with anorexia nervosa
      and other major psychiatric disorders, to defenses in healthy adolescents.
      METHOD: Thirty-seven patients with anorexia nervosa, 30 with major depressive
      disorder, 20 with obsessive-compulsive disorder, 53 with borderline personality
      disorder, 60 with schizophrenia, and 81 healthy controls were assessed with
      Pfeffer's Ego Defense Scale. RESULTS: Regression, denial, projection, repression,
      introjection, and total defenses were common to all psychiatric patients and
      distinguished them from normal adolescents. In addition to these defenses,
      anorectic patients also used intellectualization more frequently than normal
      adolescents and psychiatric patients. They used sublimation more than other
      psychiatric patients. Patients with disorders, apart from obsessive-compulsive
      disorder, that are considered to be often comorbid with anorexia did not have
      different defense than schizophrenic patients. CONCLUSIONS: Anorectic adolescents
      overutilize relatively more mature defenses than do psychiatrically ill
      adolescents, and they overutilize immature defenses compared with normal
      adolescents. This combination of mature and immature defenses may be related to
      the uniquely heterogeneous ego functioning seen in anorectic patients, and it may
      provide insight into the nature of the psychopathology of anorexia nervosa. It
      also could have important psychotherapeutic and prognostic value.

PMID- 8543537
TI  - Itard's 1828 memoire on "Mutism caused by a lesion of the intellectual
      functions": a historical analysis.
AB  - OBJECTIVE: To demonstrate that Itard was one of the first clinicians to describe
      autism (which Itard named "intellectual mutism") and effectively separate these
      cases from mental retardation. Known for his attempts at rehabilitation of the
      Wild Boy of Aveyron, Itard wrote a largely unacknowledged paper in 1828 on the
      different causes of "intellectual mutism," the result of 28 years of observations
      at the Institut des Sourd-Muets in Paris. METHOD: Itard emphasized a complete
      examination of the child's faculties including attention, memory, and imitative
      capacity. He also described the behavior of these children as unsocialized, with
      poor peer relationships, superficial contact with adults in order to satisfy
      their own needs, and difficulties in language, especially with pronouns. RESULTS:
      He then described his various diagnostic and treatment approaches to determine
      whether the child can regain language and is educable. His description of the key
      features of intellectual mutism is compared to Kanner's classic description of
      autism. CONCLUSION: Itard rejected the overly inclusive diagnosis of "idiocy" and
      offered a way to distinguish children with mental retardation from those with
      pervasive developmental disorders, described key clinical features, and offered
      an assessment and treatment of these cases, all before 1830. His contribution
      should be recognized in textbooks of child psychiatry and developmental
      disorders.

PMID- 8543538
TI  - Asperger's syndrome and autism: differences in behavior, cognition, and adaptive
      functioning.
AB  - OBJECTIVE: To determine whether subtypes of children with pervasive developmental
      disorder (PDD) differed on variables that were relatively independent of
      distinguishing criteria. METHOD: Higher-functioning children with PDD, 4 through
      6 years of age, were differentiated into those with autism (n = 47) and those
      with Asperger's syndrome (n = 21) on the basis of delayed and deviant language
      development. The groups were then compared on a wide range of measures including
      PDD symptoms, adaptive behaviors in communication, socialization, and activities
      of daily living, and an assessment of verbal and nonverbal cognitive skills.
      RESULTS: Significant differences between the groups existed on many PDD symptoms,
      adaptive behaviors, and cognitive measures of language competence, but not on
      aspects of nonverbal communication, nonverbal cognition, or motor development.
      CONCLUSION: Subtypes of children with PDD can be identified that differ on
      variables relatively independent of defining characteristics. These findings
      should provide a firm foundation into research to determine whether children with
      autism and Asperger's syndrome also differ on outcome, etiology, and response to
      treatment.

PMID- 8543539
TI  - Psychotropic and anticonvulsant drugs in subjects with autism: prevalence and
      patterns of use.
AB  - OBJECTIVE: To survey the prevalence and patterns of psychotropic and
      anticonvulsant medication and vitamin treatments in patients with autism. METHOD:
      Caregivers of 1,595 index cases were sent survey questionnaires by mail, and
      repeat questionnaires were sent twice if no reply was received. RESULTS: A total
      of 838 care providers (53%) responded to the survey. In all, 33.8% of the sample
      was taking some psychotropic drug or vitamin for autism or associated
      behavioral/psychiatric problems. A total of 19.2% reported having epilepsy, but
      only 13.2% were taking anticonvulsant drugs. More than 50% of the sample was
      taking some psychotropic, antiepileptic, vitamin, or "medical" agent. Of the
      agents taken, care providers were most satisfied with anticonvulsants,
      antidepressants, and stimulants. The use of each drug group was analyzed with
      respect to subject and demographic variables to evaluate medication patterns
      within this population. CONCLUSION: As in the often related clinical population
      of mental retardation, psychotropic medication appears to be heavily used in
      patients with autism.

PMID- 8543540
TI  - Russian roulette: a case of questions not asked?

PMID- 8543541
TI  - The use and tolerability of fluoxetine in geropsychiatric inpatients.
AB  - BACKGROUND: The efficacy and tolerability of fluoxetine were examined in 31
      patients admitted to a geropsychiatric inpatient unit who were initiated and
      maintained on a regimen of fluoxetine. METHOD: The Hamilton Rating Scale for
      Depression, the Brief Psychiatric Rating Scale, the Mini-Mental State
      Examination, and the Rating Scale for Side Effects were administered at admission
      and discharge, and scores were compared using paired t tests. Two patients were
      withdrawn from fluoxetine prior to discharge because of side effects; their data
      are not included in the analysis. RESULTS: We found significant improvement both
      in depressive symptoms and in general psychiatric symptoms and nonsignificant
      improvement in cognitive function. Fluoxetine was well-tolerated, and a
      significant decrease in the total scores of the Rating Scale for Side Effects was
      found. Subgroups of older patients (mean age = 75 years), less depressed
      patients, and demented patients were also examined. In all three groups, we found
      a statistically significant improvement in depressive symptoms, general
      psychiatric symptoms, and total side effects. CONCLUSION: Fluoxetine appears to
      be an effective and well-tolerated antidepressant in elderly inpatients of
      varying age, levels of depression, and psychiatric diagnoses.

PMID- 8543542
TI  - The relationship between antimanic agent for treatment of classic or dysphoric
      mania and length of hospital stay.
AB  - BACKGROUND: This retrospective study was conducted to evaluate the relationship
      between the mood-stabilizing agents lithium, carbamazepine, and divalproex sodium
      and time course of drug response as measured by length of hospital stay. METHOD:
      Seventy-eight patients were evaluated. Discharge date and length of
      hospitalization were obtained by review of the dictated discharge summary by
      investigators who were blind to medication status. Drug choice, including blood
      levels, was then identified as well as any adjunctive treatment. Statistical
      evaluation (SAS software) of time to improvement was conducted using
      nonparametric survival models. Possible confounding variables were assessed by
      parametric survival regression models and proportional hazards models. RESULTS:
      The individual survival curves of four major antimanic treatment groups revealed
      a significant difference by the second week of hospitalization in the divalproex
      sodium and the lithium/carbamazepine combination groups as compared with the
      lithium or carbamazepine groups (chi 2 = 13.83, df = 3, p = .003). The mean +/-
      SD length of stay was approximately 40% shorter for the divalproex sodium (10.2
      +/- 2.0 days) and the lithium/carbamazepine combination (11.7 +/- 2.1 days)
      groups compared with the lithium alone (17.6 +/- 1.0 days) and the carbamazepine
      alone (18.1 +/- 3.0 days) groups. Regression analysis of possible confounding
      variables including adjunctive treatment (benzodiazepines and neuroleptics),
      severity of illness (number of years ill and previous hospitalizations), and
      discharge date revealed no statistically significant effect. CONCLUSION:
      Shortcomings of our study include those inherent in the design of a non
      randomized, small naturalistic study and retrospective chart review. Our study
      does, however, suggest different drug response rates for the treatment of classic
      and dysphoric mania and warrants further controlled investigation.

PMID- 8543543
TI  - A cross-sectional study of parkinsonism and tardive dyskinesia in lithium-treated
      affective disordered patients.
AB  - BACKGROUND: The purpose of this study was to investigate the prevalence of
      extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) in affective disordered
      patients treated with lithium and to study the association of these symptoms with
      medication and other factors. METHODS: This cross-sectional study was carried out
      in all consenting outpatients attending an affective disorders clinic in a
      psychiatric hospital. The study sample consisted of 130 stable outpatients: 110
      with bipolar disorder, 18 with unipolar (major) depression, and 2 with atypical
      affective disorder. At the time of evaluation, 110 patients were receiving
      lithium, 37 in combination with antidepressants and 19 with neuroleptics, and 40
      had a history of neuroleptic treatment during the previous 6 months. The patients
      were assessed with the Extrapyramidal Symptom Rating Scale (ESRS) for
      parkinsonism, akathisia, dystonia, and TD. The prevalence of these symptoms was
      calculated for all patients and by current lithium and neuroleptic intake.
      Multiple linear regression analysis was used to investigate the relationship
      between the ESRS subscale scores and gender, age, diagnosis, and medication type.
      RESULTS: The prevalence of tremor was 20.8%; hypokinetic parkinsonism, 7.7%;
      akathisia, 4.6%; dystonia, 3.8%; and TD, 9.2%. Tremor was associated with lithium
      and neuroleptic intake; hypokinesia was associated with neuroleptic treatment and
      age; and TD was associated with neuroleptic, lithium, and tricyclic intake and
      age. Seven of 51 patients taking lithium but without a history of neuroleptic
      treatment during the previous 6 months presented symptoms of TD. CONCLUSION: The
      combination of lithium and neuroleptics was associated with a high prevalence of
      EPS. The presence of TD in lithium-treated patients not treated with neuroleptics
      for at least 6 months is consistent with the hypothesis that lithium may
      exacerbate the vulnerability of affective disordered patients to dyskinesias.

PMID- 8543544
TI  - Risperidone as a treatment for Tourette's syndrome.
AB  - BACKGROUND: An open-label trial was performed to assess the efficacy and safety
      of risperidone, a benzisoxazole derivative with potent D2 and 5-HT2 antagonism,
      for treatment of Tourette's syndrome. METHOD: Thirty-eight patients with
      Tourette's syndrome volunteered to take risperidone for treatment of their tics.
      All patients had failed to respond adequately to conventional treatments (with
      neuroleptics such as haloperidol and/or with the alpha 2-adrenergic agonist
      clonidine) or had suffered from intolerable side effects from such treatments.
      Patients were rated for tic severity by the Yale Global Tic Severity Scale
      (YGTSS) before treatment and after 1 month of treatment with risperidone.
      Patients were monitored carefully for side effects and clinical response.
      RESULTS: Of the 38 patients, 8 discontinued risperidone treatment before the end
      of the trial because of intolerable side effects. At the end of the 4-week trial,
      22 patients (58%) were improved, 7 patients (18%) had no appreciable change in
      their symptoms, and 1 patient (3%) had a documented worsening of tics. Doses of
      risperidone at the end of the trial ranged from 0.5 mg to 9 mg/day (mean = 2.7
      mg/day). CONCLUSION: This open clinical trial suggests that risperidone may be a
      promising alternative to conventional medications used for treating the symptoms
      of Tourette's syndrome.

PMID- 8543545
TI  - Electroconvulsive therapy and resistant depression: clinical implications of
      seizure threshold.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) were treated with
      electroconvulsive therapy (ECT) to determine (1) variability of initial seizure
      threshold, (2) factors that influence seizure threshold, (3) change in seizure
      threshold during the ECT course, and (4) relationship of seizure threshold to
      antidepressant effects. METHOD: Seizure threshold was measured by a stimulus
      titration technique during the first, eighth, and final ECT of medication-free
      patients who had MDD, endogenous subtype based on Research Diagnostic Criteria
      and were randomly assigned to three-times-weekly, bilateral, brief pulse ECT (N =
      24) or twice-weekly ECT plus one simulated treatment per week (N = 23).
      Subsequent to the first ECT, stimulus intensity was 1.3 to 1.8 (median = 1.5)
      times threshold. The Hamilton Rating Scale for Depression (HAM-D) was the primary
      clinical outcome measure. RESULTS: Initial seizure threshold varied by 594%.
      Gender (p = .03), total strength of pre-ECT pharmacotherapy trials (p = .02), and
      age (p = .12) accounted for 23.9% of the variance. Threshold increased by 42% +/-
      26% (p = .0001) from the first to the final ECT, and seizure duration decreased
      by 33% +/- 28% (p = .0001). Seizure duration and mean stimulus intensity were
      negatively associated over all treatments (r = -.49, p = .0003). Change in HAM-D
      score was related to duration of the current depressive episode (r = -.39, p =
      .006) and total strength of pre-ECT pharmacotherapy trials (r = -.39, p = .008),
      but not to seizure threshold or duration. CONCLUSION: (1) Initial seizure
      threshold for pulse bilateral ECT is highly variable and not yet amenable to
      accurate prediction. (2) Stimulus titration allows threshold to be determined on
      an individual basis and dosage for subsequent treatments to be defined. (3)
      Seizure duration is of limited value as a sole criterion for the adequacy of
      treatment when initial threshold is unknown and/or electrical doses that
      substantially exceed threshold are used. (4) With moderately suprathreshold
      bilateral ECT, a relationship of seizure threshold to antidepressant response is
      not demonstrable.

PMID- 8543546
TI  - Paroxetine level in breast milk.

PMID- 8543547
TI  - Bladder dysfunction associated with clozapine therapy.

PMID- 8543548
TI  - Withdrawal dyskinesia after abrupt cessation of clozapine and benztropine.

PMID- 8543549
TI  - Eosinophilia associated with decreasing neutrophil count in a clozapine-treated
      patient.

PMID- 8543550
TI  - Mania associated with risperidone use.

PMID- 8543551
TI  - Hyperlithemia correction: an untraditional view.

PMID- 8543552
TI  - Dosage titration issues.

PMID- 8543553
TI  - Practical approaches to the treatment of panic disorder.

PMID- 8543554
TI  - Sertraline versus desipramine in the treatment of premenstrual syndrome: an open
      label trial.
AB  - BACKGROUND: Antidepressant medications have appeared to be effective treatments
      for premenstrual syndrome (PMS) in several small trials. This open-label study
      examined the efficacy of and tolerance for a new serotonergic antidepressant
      compared with a traditional tricyclic antidepressant in PMS treatment. METHOD:
      For two menstrual cycles in women meeting well-defined criteria for PMS, an open
      label comparison of the serotonin selective sertraline (N = 17) and the
      noradrenergic desipramine (N = 15) was performed. Dose was flexible, with a mean
      dose in the second cycle of 87 mg/day for sertraline and 110 mg/day for
      desipramine. Outcome measures were the premenstrual daily symptom report (DSR)
      scores and the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Sertraline
      and desipramine reduced depressive symptoms as assessed by the HAM-D, both
      achieving similar reductions in the HAM-D scores. Reduction of total premenstrual
      symptoms as assessed by the DSR score was observably greater with sertraline, but
      the difference compared with desipramine was not statistically significant in
      this small sample. Subjects were more likely to perceive desipramine side effects
      as intolerable; 4 of the 15 desipramine-treated subjects discontinued compared
      with none in the sertraline group. Subjects who were previously treated in a PMS
      program without good therapeutic response were less likely to respond to either
      medication, suggesting a treatment-resistant group. CONCLUSION: Sertraline and
      possibly desipramine appear to be effective treatments for PMS. Sertraline was
      better tolerated, resulting in greater patient acceptance. A placebo-controlled
      trial in which subjects are randomly assigned to the medication is clearly needed
      to support or refute these preliminary findings.

PMID- 8543555
TI  - Ribozymes: from mechanistic studies to applications in vivo.
AB  - The hammerhead ribozyme belongs to the class of molecules known as antisense
      RNAs. However, because of short extra sequences that form the so-called catalytic
      loop, it can act as an enzyme. Since the catalytic domain captures magnesium ions
      and magnesium ions can cleave phosphodiester bonds, hammerhead ribozymes are
      recognized as metalloenzymes. In general, the cleavage of phosphodiester bonds
      involves acid/base catalysis, with proton transfer occurring in the transition
      state. When the possibility of such a proton-transfer process was examined by
      measuring solvent isotope effects, it became apparent that no proton transfer
      occurs in the transition state during reactions catalyzed by a hammerhead
      ribozyme. It is likely, therefore, that hammerhead ribozymes exploit the general
      double-metal-ion mechanism of catalysis, with Mg2+ ions coordinating directly
      with the attacking and leaving oxygen moieties. Since the hammerhead ribozyme is
      one of the smallest RNA enzymes known and has potential as an antiviral agent,
      thus ribozyme has been extensively investigated for applications in vivo.
      Ribozymes are described that have possible utility as agents against HIV-1.

PMID- 8543556
TI  - Role of acyl coenzyme A cholesterol acyltransferase in intrahepatic processing of
      apo B-lipoprotein in suncus.
AB  - We have previously shown that fatty liver was easily induced in suncus by
      starvation and that the plasma level of apolipoprotein B (apoB) was very low. We
      also previously reported that a defect in the assembling process of apo B
      containing lipoprotein (very low density lipoprotein, VLDL) may be one of the
      reasons for the low level of plasma apo B and for induction of fatty liver by
      starvation in suncus. We also found that hepatic acyl coenzyme A cholesterol
      acyltransferase (ACAT) activity is very low in the animals, resulting in
      decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl
      ester in suncus liver may be one of the reasons for the defect in the assembling
      process of VLDL. In this study, we investigated the effect of cholesterol
      feeding, which induces an increase in triglyceride and cholesteryl ester of the
      liver as a consequence of the induction of both intestinal and hepatic ACAT
      activities, on the secretion of VLDL. Although the basal ACAT activity of
      intestinal mucosa was high, cholesterol-feeding did not induce either an increase
      in plasma lipid or an increase in intestinal ACAT activities in suncus. The
      hepatic secretion rate of VLDL was estimated by treatment with Triton WR1339,
      which is well known to inhibit the catabolism of VLDL. Cholesterol-feeding caused
      a slight increase in hepatic triglyceride and cholesteryl ester but no increase
      either in the secretion rate of VLDL or in hepatic ACAT activity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8543557
TI  - Expression of recombinant human thyrotropin receptor in myeloma cells.
AB  - Starting with a previously isolated cDNA for human thyrotropin receptor (TSHR),
      we established a transformed myeloma cell line, SP56, which expresses human TSHR
      on its cell surface. Binding analysis showed that SP56 bears 1.1 x 10(5) TSHR per
      cell with a Kd of 2.2 x 10(-10) M. Using the purified cellular membrane, we
      established a TSH binding inhibition immunoglobulin (TBII) assay for
      autoantibodies against TSHR. We compared it with the TBII assay utilizing porcine
      thyroid membranes expressing porcine TSHR, which has been widely used for TBII
      assay, by using 96 serum samples from patients with autoimmune thyroid disease
      and normal individuals. Our TBII assay was more sensitive than the one using
      porcine TSHR: of 38 sera of patients which were judged negative for
      autoantibodies to TSHR (TBII value below 10%) by the latter assay, 28 were
      positive (above 20%) in our assay. By using a perfusion culture system, we
      obtained as many as 3 x 10(10) SP56 cells, from which 3,450 mg protein of the
      membrane could be purified; this is sufficient for 15,000 assays. The results
      indicate that the membrane of the myeloma cell line SP56 is more suitable for use
      in the TBII assay than the porcine thyroid membrane, in terms of sensitivity to
      autoantibodies against TSHR in human sera.

PMID- 8543558
TI  - Stimulation of phagocytosis and phagosome-lysosome fusion by glycosphingolipids
      from Sphingomonas paucimobilis.
AB  - Sphingomonas paucimobilis, a Gram-negative opportunistic pathogen, is actively
      phagocytosed by human peripheral polymorphonuclear leukocytes (PMN) in vitro.
      However, when live or killed cells were delipidated, the phagocytic rate was
      clearly decreased. Therefore, we have investigated the physiological role of
      membrane lipids in phagocytic processes. S. paucimobilis type strain 2395
      produces four classes of acidic glycosphingolipids (GL-1, GL-2, GL-3, and GL-4)
      with the common components of glucuronic acid, 2-hydroxy myristic acid and d18:0
      or d21:1 long-chain base. The effect of acidic glycosphingolipids on phagocytosis
      by PMN using killed Staphylococcus aureus cells coated with glucuronosyl ceramide
      (GL-1) or ceramide tetrahexoside (GL-4) was also examined. The rate of phagosome
      lysosome fusion by PMN was determined by counting acridine orange-stained
      bacteria under a fluorescence microscope. Both phagocytosis and phagosome
      lysosome fusion by PMN of glycosphingolipid-coated bacteria were stimulated
      markedly in a dose-dependent manner. It was noted that GL-1 or GL-4 stimulated
      phagosome-lysosome fusion dramatically, but synthetic lipid A did not. Superoxide
      anion release from PMN was enhanced significantly by the coating with synthetic
      lipid A at higher concentration, but only slightly with GL-1 or GL-4. Glucuronic
      acid was an inhibitor of phagocytosis of GL-1-coated S. aureus by PMN. The effect
      of acidic glycosphingolipids obtained from mammalian tissue on phagocytosis was
      also compared with that of bacterial glycosphingolipids. Ganglioside GM3 and
      sulfatide showed a marked stimulative activity for phagocytosis by PMN, while the
      neutral glycosphingolipids did not. Thus, bacterial acidic glycosphingolipid and
      mammalian acidic glycosphingolipid promote phagocytosis and phagosome-lysosome
      fusion by PMN.

PMID- 8543559
TI  - Fluorescence-labeled synthetic glycopolymers: a new type of sugar ligands of
      lectins.
AB  - Radical copolymerization of a polymerizable dansyl derivative, N-2-propenyl-(5
      dimethylamino)-1-naphthalene sulfonamide, with sugar monomers and acrylamide
      proceeded smoothly in aqueous solution in the presence of ammonium persulfate and
      N,N,N',N'-tetramethylethylenediamine and afforded a novel type of water-soluble
      glycopolymers having fluorescent side-chains. Fluorescence emission spectra of
      these polymeric sugar-ligands by excitation at 340 nm revealed maxima at 448 and
      528 nm. When the glycopolymer carrying galactose residues was saturated with
      Ricinus communis agglutinin (RCA60), the fluorescence emission maxima at 448 and
      528 nm were not shifted significantly, although the fluorescence intensities were
      decreased by 20 and 14%, respectively. Polymeric sugar-cluster effects
      drastically enhanced the association constants of galactose residues with RCA60
      in the order of 10(8) M-1. The significance for efficient binding of galactose
      density on the glycopolymer was also demonstrated by using glycopolymers with
      different degrees of galactose branching.

PMID- 8543560
TI  - Expression and kinetic properties of a recombinant 3 alpha
      hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver.
AB  - Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid
      dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase
      activity, and multiple cDNAs for the enzymes have been cloned from human liver
      cDNA libraries. To understand the relationship of the multiple enzyme froms to
      the genes, a cDNA, which has been reported to code for an isoenzyme of human
      liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in
      Escherichia coli. The recombinant enzyme showed structural and functional
      properties almost identical to those of the isoenzyme purified from human liver.
      In addition, the recombinant isoenzyme efficiently reduced 5 alpha
      dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human
      liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously
      purified, which suggests that these human liver enzymes are identical.
      Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol
      oxidation by the recombinant isoenzyme were consistent with a sequential ordered
      mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme
      much more potently than it did the other human liver dihydrodiol dehydrogenases,
      and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+
      complex.

PMID- 8543561
TI  - Vesicular monoamine uptake by digitonin-permeabilized PC12 cells: inhibitory
      effect of neuromodulators and drugs on the amine transport.
AB  - Vesicular amine transport is crucial for activity of monoaminergic neurons since
      translocation of cytosolic amine to storage vesicles is required for both
      exocytotic release and reuptake of the neurotransmitter. We developed a
      convenient assay system for vesicular amine transport based on permeabilizing the
      plasma membrane of pheochromocytoma PC12 cells with digitonin at concentrations
      of 100 to 150 microM. Serotonin (5HT) is a better substrate than either
      epinephrine or norepinephrine in this assay system. In the presence of 2 mM ATP,
      5HT uptake by the permeabilized cells increased linearly for at least 30 min at
      25 degrees C, whereas without addition of exogenous ATP, 5HT uptake reached an
      apparent plateau after 20 min incubation. Reserpine (500 nM) completely blocked
      the ATP-dependent 5HT uptake in this system whereas nomifensine (10 microM) had
      no effect, indicating specificity for vesicular transport. Treatment of intact
      PC12 cells with AMP dose-dependently decreased 5HT uptake with an EC50 of 20-30
      microM as measured after cell permeabilization. Treatment of the intact PC12
      cells with forskolin and phorbol 12-myristate 13-acetate prior to
      permeabilization also down-regulated vesicular 5HT transport, whereas the
      addition of either of these agents into the reaction mixture for the amine uptake
      by already permeabilized cells did not alter the vesicular uptake activity. Thus,
      the system can be applied to studies on regulation of the vesicular amine
      transport by physiological signaling molecules, intracellular messengers, and
      drugs.

PMID- 8543562
TI  - Chemical modification of cationic groups of a novel alpha-neurotoxin (Oh-4) from
      king cobra (Ophiophagus hannah) venom.
AB  - The cationic groups of arginine and lysine residues in Oh-4, a novel alpha
      neurotoxin from king cobra (Ophiophagus hannah) venom were subjected to
      modification with p-hydroxyphenylglyoxal (HPG) and trinitrobenzene sulfonate
      (TNBS), respectively. Monoderivatization of Arg-35, resulted in a drastic loss in
      neurotoxicity to 25% of the native toxin. The activity was decreased to a greater
      extent with the derivative extensively modified on Arg-35, -9, and -37. The Arg
      35-modified derivative retained about a half of the antigenicity of the native
      toxin, and extensive modification on Arg-9 and Arg-37 caused a further decrease
      in the antigenicity of the toxin molecule. Selective trinitrophenylation (TNP-)
      of Lys-51 caused losses of neurotoxicity and antigenicity by 77 and 83%,
      respectively. These results indicate that Arg-35 and Lys-51 in Oh-4 have
      important roles in the neurotoxicity. In contrast to the Arg residues at 9, 35,
      and 37, Lys-51 plays a more critical role in the antigenicity.

PMID- 8543563
TI  - Molecular cloning of CWP1: a gene encoding a Saccharomyces cerevisiae cell wall
      protein solubilized with Rarobacter faecitabidus protease I.
AB  - A yeast cell wall glycoprotein with a molecular weight of 40,000, named gp40, was
      solubilized from SDS-extracted cell wall of Saccharomyces cerevisiae by
      incubation with Rarobacter faecitabidus protease I, which is a yeast-lytic
      enzyme. Based on its amino acid sequence, we cloned and sequenced the gene
      encoding the precursor of gp40, named CWP1; cell wall protein gene. The DNA
      sequence of the CWP1 gene was identical to YKL443, an open reading frame
      identified in a genome sequencing program for yeast chromosome XI. This gene
      encoded a serine-rich protein of 239 amino acids with a molecular weight of
      24,267. The presence of hydrophobic sequences in the N- and C-termini of the CWP1
      protein suggests that it is secreted as a glycosylphosphatidylinositol-anchored
      protein and is subsequently integrated into the cell wall. Since a gene
      disruption experiment showed no growth defect, the CWP1 gene is not essential for
      growth. Mutant CWP1 protein deficient in the C-terminal hydrophobic sequence was
      secreted into the culture medium, not anchored to the cell wall, thereby
      indicating that this hydrophobic sequence plays a crucial role in anchoring to
      the cell wall. Homology between the CWP1 protein and TIP1 family of cold shock
      proteins suggests that they belong to a new family of cell wall proteins.

PMID- 8543564
TI  - Effects of protein tyrosine kinase inhibitors with different modes of action on
      topoisomerase activity and death of IL-2-dependent CTLL-2 cells.
AB  - We studied the effects of protein tyrosine kinase inhibitors with different modes
      of action on topoisomerase activity and cell death in CTLL-2 cells, whose growth
      is IL-2-dependent. The Flavonoids genistein, biochanin A, and apigenin inhibited
      topoisomerase II to the same extent as etoposide, a specific inhibitor of the
      enzyme. Methyl 2,5-dihydroxycinnamate (2,5-MeC) also inhibited topoisomerase II,
      but was less potent than genistein. Herbimycin A and staurosporine did not
      inhibit topoisomerase II. None of the inhibitors of protein tyrosine kinases
      examined inhibited topoisomerase I activity. All the inhibitors induced cell
      death with internucleosomal DNA fragmentation in the presence of IL-2. Genistein,
      biochanin A, and apigenin induced DNA fragmentation and cell death early in the
      incubation period and did not alter the profiles of phosphotyrosine proteins in
      either the lysate or pelleted fractions, indicating that the early cell death was
      induced by the inhibition of topoisomerase II activity rather than by the
      inhibition of protein tyrosine kinase activity. 2,5-MeC similarly induced early
      cell death and DNA fragmentation, but to a lesser extent than genistein
      presumably due to the inhibition of topoisomerase II activity. Herbimycin A
      induced a slow increase in DNA fragmentation and cell death, accompanied by a
      decrease in phosphotyrosine proteins in the pelleted fraction, suggesting that
      the inhibition of protein tyrosine phosphorylation, presumably of the nuclear
      proteins, is related to cell death and DNA fragmentation. Staurosporine-induced
      DNA fragmentation appeared to be due to mechanism(s) other than the inhibition of
      topoisomerases and protein tyrosine kinases, since it neither altered the
      profiles of phosphotyrosine proteins nor inhibited topoisomerase activity.

PMID- 8543565
TI  - Cloning and sequence analysis of the gene for phosphoenolpyruvate carboxylase
      from an extreme thermophile, Thermus sp.
AB  - The ppc gene, which encodes phosphoenolpyruvate carboxylase (PEPC) of an extreme
      thermophile, Thermus sp., was cloned and sequenced. The ppc gene had a high G+C
      content (69.2%). An open reading frame for a 857-amino-acid polypeptide was found
      in the gene. The calculated molecular mass was 95,632. The amino acid sequence of
      Thermus PEPC was 31-37% identical and 52-57% similar to those of 17 PEPCs from
      mesophilic organisms. No Cys residue was found in the polypeptide, demonstrating
      that this residue is not essential for the catalytic activity of PEPC. The cloned
      gene was expressed in Escherichia coli and thermostable PEPC was obtained.

PMID- 8543566
TI  - Effects of protein kinase C and A activation on ATP-stimulated release of
      [3H]noradrenaline from PC12 cells.
AB  - The influence of activation of protein kinase C (PKC) and cyclic AMP on
      noradrenaline (NA) release in the neurosecretory rat pheochromocytoma PC12 cell
      line was investigated. External ATP induced [3H]NA release from prelabeled PC12
      cells, in the presence of extracellular CaCl2. The potency order of ATP analogs
      was adenosine 5'-O-(gamma-thiotriphosphate) > or = ATP > 2-methylthio ATP > 2',3'
      O-(4-benzoyl)benzoyl ATP. alpha,beta-Methylene ATP, beta gamma-methylene ATP, and
      8-bromo ATP were inactive. Neither ADP, GTP, nor ITP was active. The addition of
      phorbol 12-myristate 13-acetate (PMA) or agents elevating the cyclic AMP content,
      such as vasoactive intestinal peptide (VIP) or an adenosine analog, also
      stimulated [3H]NA release. Not only high K(+)- but also ATP-stimulated [3H]NA
      release was enhanced by co-addition with PMA or agents elevating the cyclic AMP
      content. PMA and VIP had no effect on the cytosolic free Ca2+ concentration
      ([Ca2+]i) or on the ATP-stimulated [Ca2+]i rise, although both stimulatory
      effects on [3H]NA release were dependent on extracellular CaCl2. The addition of
      PMA stimulated [3H]NA release dose-dependently, and enhanced 300 microM (maximal
      dose) ATP-stimulated [3H]NA release without changing the affinity for ATP. The
      effect of PMA was inhibited by PKC inhibitors such as calphostin C and in PKC
      depleted cells, and potentiated by elevation of cyclic AMP. These data suggest
      that the process of ATP-stimulated NA release, not ATP-stimulated Ca2+ influx, is
      regulated by the dual, PKC- and cyclic AMP-dependent mechanisms, positively and
      independently. Treatment with pertussis toxin had no effect on the ATP-stimulated
      [Ca2+]i rise or [3H]NA release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8543567
TI  - Rat epidermal cathepsin L-like proteinase: purification and some hydrolytic
      properties toward filaggrin and synthetic substrates.
AB  - We have purified cathepsin L-like proteinase from rat epidermis, determined its
      NH2-terminal amino acid sequence, and investigated its proteolytic activities on
      an intermediate filament-associated protein filaggrin and several synthetic
      substrates. The amino acid sequence of its NH2-terminus was determined to be Val
      Pro-Asn-Ser-Leu-Asp-Trp-Arg-Glu-Lys-Gly-Tyr-Val-Thr-Pro-, which differed from
      that of rat cathepsin L and was not found in the amino acid sequence data bank.
      The enzyme consisted of a single-chain form with M(r) 30,000. Its hydrolytic
      properties toward synthetic substrates were similar to those of cathepsin L in
      other tissues. The enzyme effectively proteolyzed rat epidermal filaggrin into
      small fragments at pH 4.0-6.0 and was inhibited by a specific cysteine proteinase
      inhibitor, N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)L-leucyl]-agmatin. However,
      cathepsins D and E from rat epidermis did not hydrolyze filaggrin. This study
      demonstrated that filaggrin was susceptible to degradation by rat epidermal
      cathepsin L-like proteinase, suggesting that this proteolytic activity may have
      relevance to skin differentiation, in which acid proteases are thought to
      participate.

PMID- 8543568
TI  - Molecular cloning, nucleotide sequence, and expression of the gene encoding a
      trypsin-like protease from Streptomyces erythraeus.
AB  - Streptomyces erythraeus produces an extracellular mammalian-type serine protease
      bearing trypsin-like substrate specificity. The gene encoding the protease was
      cloned and sequenced as an initial step for investigating its structure-function
      relationship by site-specific mutagenesis. The cloned gene is composed of an 816
      bp open reading frame encoding 272 amino acid residues, suggesting that it is
      synthesized as a precursor protein containing a 42-residue prepropeptide. In the
      N-terminal prepropeptide portion, the tract of 30 residues from the initiator
      methionine has a typical signal sequence for Streptomyces and the remaining 12
      residues are thought to comprise a propeptide. The cloned gene was replaced
      downstream of a strong promoter in a high expression plasmid, pSEV2, and
      expressed in Streptomyces lividans TK24. The gene product was secreted
      extracellularly and identified as an inactive precursor which consists of the
      mature enzyme and the 12-residue N-terminally extended peptide chain. The
      precursor protein was converted to a fully active mature form by limited
      proteolysis with alpha-chymotrypsin at the Phe-(-1)-Ile-1 bond. Protein sequence
      analysis revealed that, except for the C-terminal three residues, recombinant SET
      is identical with the native enzyme.

PMID- 8543569
TI  - Molecular cloning, expression, and characterization of chaperonin-60 and
      chaperonin-10 from a thermophilic bacterium, Thermus thermophilus HB8.
AB  - The gene coding a chaperonin from a thermophilic bacterium, Thermus thermophilus
      HB8, was cloned and sequenced. The operon structure was the same as those of
      other bacterial chaperonins and the deduced amino acid sequences of both subunits
      were highly homologous to those of other chaperonins. The cloned genes of
      chaperonin subunits, chaperonin-10 (T.th cpn10) and chaperonin-60 (T.th cpn60),
      were separately expressed in Escherichia coli cells. The expressed subunits were
      easily purified from other host proteins including GroE, a chaperonin of E. coli.
      T.th cpn60 was expressed as a tetradecameric form, like GroEL of E. coli. Since
      chaperonin from T. thermophilus HB8 is purified as a holochaperonin, a complex of
      tetradecameric T.th cpn60 and heptameric T.th cpn10, a tetradecamer of T.th cpn60
      without T.th cpn10 has not been obtained before. T.th cpn60 tetradecamer tended
      to dissociate into monomers during storage. T.th cpn10 expressed in E. coli was
      purified as a stable oligomer, most likely a heptamer. The activity as holo
      chaperonin was reconstituted by mixing both subunits. T.th cpn60 tetradecamer
      itself arrested refolding of other proteins. The monomerized T.th cpn60 was
      easily purified from T.th cpn60 oligomer by gel permeation chromatography. Thus
      obtained T.th cpn60 monomer had an ATP-independent chaperone activity, as shown
      for T.th cpn60 monomer isolated from authentic holo-chaperonin.

PMID- 8543570
TI  - Enhancement of gamma-actin protein during liver regeneration: its accumulation in
      a region adjacent to the hepatocyte plasma membrane.
AB  - We identified a protein with a molecular weight of about 44 kDa in an extract of
      rat regenerating liver. This protein was undetectable in normal, sham-operated,
      and completely regenerated liver. We also purified this 44-kDa protein from an
      extract of rat liver remnant after partial hepatectomy. The partial amino acid
      sequences of the purified protein were identical to those of gamma-actin in non
      muscle cells. In addition, anti-pan actin antibody recognized the purified 44-kDa
      protein, whereas anti-muscle actin and anti-beta-actin antibodies did not. Thus,
      we concluded that the 44-kDa protein was non-muscle gamma-actin. An
      immunohistochemical study revealed that the non-muscle gamma-actin accumulated
      next to the plasma membrane of liver parenchymal cells during regeneration.
      Moreover, the gamma-actin level was augmented in primary cultured rat hepatocytes
      prior to DNA synthesis. Intracellular gamma-actin in cultured hepatocytes was
      distributed across the entire basal plane after stimulation with hepatocyte
      mitogens. This change in the distribution of gamma-actin correlated with the cell
      spreading that occurred during the G1/S phase transition. These findings
      indicated that gamma-actin plays specific roles in the growth of liver
      parenchymal cells during liver regeneration.

PMID- 8543571
TI  - Comparison of Ca2+/calmodulin-dependent protein kinase IV from rat brain,
      expressed in insect cells, and expressed in Escherichia coli.
AB  - Calmodulin-dependent protein kinase IV (CaM-kinase IV) is thought to play crucial
      roles in the functioning of Ca2+ in the central nervous system and immune system,
      and the regulation of its activity is therefore very important. Recombinant CaM
      kinase IV is invaluable for studies of its regulatory mechanism, because of its
      large-amount availability and ready site-specific mutagenesis. In the present
      study, rat CaM-kinase IV was expressed in Sf9 cells and Escherichia coli, and the
      kinetic properties were examined with syntide-2 and peptide-gamma as substrates.
      The recombinant enzymes were produced highly efficiently, comprising as much as
      about 15% of the total protein in Sf9 cells and 9% in E. coli. The brain enzyme
      shows two Km values for syntide-2 in the presence of Ca2+/calmodulin, but the
      recombinant enzymes showed normal kinetic behavior. The brain enzyme and Sf9
      enzyme showed Km values for peptide-gamma of 53 and 82 microM, respectively, but
      the Km of the E. coli enzyme was as high as 1.7 mM, in the presence of
      Ca2+/calmodulin. Thus, the three enzymes differed in their kinetic properties,
      but all the three were markedly activated upon incubation with CaM-kinase IV
      kinase under the Ca2+/calmodulin-dependent protein phosphorylation conditions.

PMID- 8543572
TI  - Inhibition of neurite outgrowth in murine neuroblastoma NS-20Y cells by
      calmodulin inhibitors.
AB  - The roles of protein kinases and calmodulin in regulating neurite outgrowth in
      murine neuroblastoma NS-20Y cells were investigated by testing the effect of
      various inhibitors on the neuritogenesis induced by serum deprivation. The
      percentage of cells with neurites was low (1-3%) in medium containing 10% serum,
      but reached about 50-60% when the cells were cultured for 24 h in serum-free
      medium. W-7 (10 microM), calmidazolium (0.3 microM), and trifluoperazine (0.1
      microM), drugs reported to inhibit calmodulin-dependent events, reduced neurite
      outgrowth. On the other hand, H-7 (inhibitor of protein kinase C and cyclic AMP
      dependent protein kinase) and H-89 (inhibitor of cyclic AMP-dependent protein
      kinase) were ineffective. Genistein (inhibitor of protein tyrosine kinase) and
      wortmannin (inhibitor of phosphatidylinositol 3-kinase) did not affect the number
      of cells with neurites. Activation of protein kinases, which is blocked by these
      inhibitors, does not appear to be essential to the extension and maintenance of
      neurites. KN-62 and KN-93 (inhibitors of Ca2+/calmodulin-dependent protein kinase
      II) were also tested but did not inhibit neurite outgrowth. These results suggest
      that a calmodulin-dependent process, other than the activation of Ca2+/calmodulin
      dependent protein kinase II, is involved in the neuritogenesis in murine
      neuroblastoma NS-20Y cells in serum-free medium.

PMID- 8543573
TI  - Localization and characterization of a novel receptor for endothelin in the gills
      of the rainbow trout.
AB  - Endothelin (ET) receptors were identified in trout tissues that included the
      gill, heart, liver, kidney, and intestine. Since both the presence and the
      physiological function of endothelin-1 (ET-1) in trout gills have been
      determined, we examined the localization and characterization of ET receptors in
      the gills. Ligand specificity of the receptors, determined by using members of
      the endothelin family, revealed that endothelin receptors specific for ET-1 were
      predominant in the gills, but the binding sites of such receptors had low
      affinity for BQ-123, which is selective for mammalian endothelin A receptors
      (ETA). We propose that this subtype of receptor be called a fish-type ETA
      receptor (ETAF) to distinguish it from the mammalian ETA receptor. Affinity
      labeling of binding sites on gill membranes with 125I-labeled ET-1 and the cross
      linking reagent 1,5-difluoro-2,4-dinitrobenzene revealed one major protein with
      an M(r) of 58,000, similar to that found in mammals. Autoradiographic studies
      demonstrated a high density of endothelin-binding sites in the lamellar sinusoid,
      which is involved in gas exchange in gills. No binding was detected in the
      chondrocytes or cartilaginous matrix. Our observations suggest that the
      endothelin and ET receptor system found in mammals might play a physiological
      role in the regulation of metabolic functions in fish.

PMID- 8543574
TI  - Genomic organization and isoforms of the mouse ELP gene.
AB  - Analysis was made on the genomic structure, functions, and expression of the
      mouse ELP gene, which codes for the embryonal long terminal repeat binding
      protein. Extensive screening of the cDNA library of embryonal carcinoma cells (EC
      cells) identified four isoforms of ELP: ELP1 (the original ELP isolate), ELP2,
      ELP3, and Ad4BP/SF1. Analysis of the genomic sequences revealed that these ELP
      isoforms were generated by alternative promoter usage and differential splicing.
      The mRNAs of isoforms initiated at four transcription start sites distributed on
      three exons. Sequence analysis of the four isoforms identified three
      polypeptides. The N-terminal portion of ELP1 and ELP2 was longer than ELP3, and
      Ad4BP/SF1 by 77 aa. The DNA-binding domain and region II were shared by all four
      isoforms. The C-terminal portion shared by ELP2, ELP3, and Ad4BP/SF1 was 131 aa
      in length, and that specific to ELP1 was 57 aa in length. The ELP3 and Ad4BP/SF1
      isoforms were identical for the coding sequence, but the two differed at the 5'
      noncoding region. Region II and III domains of nuclear receptors were thought to
      be involved in ligand-binding and transcriptional activation. ELP1, which lacked
      region III, functioned as a repressor. The isoforms carrying intact region II and
      region III functioned as transactivators. Expression of the four isoforms was
      studied in mouse tissues and in tissue culture cells by quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis. Complex patterns of
      expression of these isoforms were observed in various tissues. All four ELP
      isoforms were expressed only in EC cells.

PMID- 8543575
TI  - In vitro mRNA synthesis by Sendai virus: isolation and characterization of the
      transcription initiation complex.
AB  - We have developed an in vitro transcription system using purified Sendai virus
      particles in which viral mRNA synthesis is almost entirely dependent on the
      addition of cellular proteins (host factors), one of which can be replaced by
      highly purified cellular tubulin [Mizumoto et al. (1995) J. Biochem. 117, 527
      534]. In this study, to elucidate the function of host factors in transcription,
      we isolated an active initiation complex as a viral ribonucleoprotein, by
      incubating virus particles with bovine brain extract in the absence of nucleoside
      triphosphates, followed by ultracentrifugation. RNA products from the isolated
      initiation complex contained six mRNA species corresponding to all the virus
      encoded genes, and most of them had a 5'-cap structure as well as a 3'-poly(A)
      tail. Immunoblotting showed that tubulin was specifically associated in the
      active complex. These data suggest that cellular tubulin, one of the host factors
      essential for Sendai virus transcription, interacts with the viral
      ribonucleoprotein to form an active complex at the initiation step.

PMID- 8543577
TI  - Ultrastructural and biochemical modifications of collagen from tissue of Morbus
      Dupuytren patients.
AB  - Small angle X-ray diffraction and biochemical analyses were carried out on normal
      palmar aponeurosis and on tissue from patients suffering from Dupuytren
      contractures (MD). Pathological tissue exhibits a higher overall content of
      collagen III. Type I collagen extracted from pathological tissue has a melting
      point of 0.8 degrees C higher than that of normal collagen. The only chemical
      differences compared to normal collagen I are 50% overhydroxylation of lysyl
      residues and a reduced amount of diglycosylated hydroxylysine residues. Analysis
      of the electron density distribution inside the collagen repeating period of MD
      samples reveals disordered molecular packing in MD samples compared to in normal
      collagen. The disorder, which is higher in the gap region, is considerably
      reduced upon stretching.

PMID- 8543576
TI  - Malfolded cytochrome P-450(M1) localized in unusual membrane structures of the
      endoplasmic reticulum in cultured animal cells.
AB  - A conserved region containing three to five proline residues is present just
      behind the signal-anchor sequence in the amino terminal portion of most
      microsomal cytochrome P-450s. We have shown that the proline residues are crucial
      for correct folding in Schizosaccharomyces pombe cells by using mutants of P
      450(M1) in which one to three of the proline residues were changed to alanine. To
      examine the effects of the mutations on the intracellular localization of P-450s,
      they were expressed in COS-7 cells. They were found to be localized only in the
      perinuclear loci as patched structures like the Golgi apparatus, while the wild
      type P-450(M1) is localized in the reticular structures which are typical for the
      ER membrane. However, treatment of the cells with Brefeldin A had no effect on
      the patched structures. Upon co-expression with another ER membrane protein,
      CD4D, which possesses a double lysine motif, the expressed CD4D was localized not
      only in the patched structures as the mutated P-450(M1)s, but also in the
      reticular structures of ER. When the cells were homogenized and then
      fractionated, the mutated P-450(M1) was recovered mainly in the low-speed
      precipitate and in the fractions of much higher density than the normal ER
      membrane. On electron microscopic observation, unusual membranous bodies were
      observed near the nucleus only when the mutated P-450(M1) was expressed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8543578
TI  - Phosphorylation of 1,5-anhydro-D-glucitol in mammalian cells.
AB  - A cyclic polyol, 1,5-anhydro-D-glucitol (AG), is generally present in animals,
      although little is known about the metabolic and physiological roles of AG in any
      type of animal cells. The present metabolic study demonstrated phosphorylation of
      AG in human chronic myelogenous leukemia cells, K-562. Phosphorylated AG (AGP)
      was also proved to be present in various rat organs; its level in most organs
      ranged between 2 and 5 nmol/g wet tissue, which amounted to 5 to 10% of the AG
      levels in the respective organs. In the spleen and brain, however, the AGP levels
      were especially high, 13.4 and 8.3 nmol/g, respectively, or 24.4 and 20.6% of the
      respective AG levels. These data suggest that AGP is an intermediary metabolite
      related to AG in animal cells.

PMID- 8543579
TI  - Guanylate cyclase activity in the inner ear and auditory nerve of the rat.
AB  - Novel molecular mediation in the sound transductional process is implicitly
      suggested. We investigated the presence of the cGMP-synthesis enzyme, guanylate
      cyclase, in Corti's organ and auditory nerve of the rat. The soluble guanylate
      cyclase activity found was sensitive to changes of sound intensity in the
      different acoustic media used, suggesting a potential role for the system that
      involves this enzyme. The guanylate cyclase activity appeared to be inversely
      related (in the inner ear) with the sound intensity to which the animals were
      exposed; different behavior was observed for the auditory nerve. The enzymatic
      activity found in Corti's organ, a direct bio-receptor of sound, represents the
      first reported enzymatic activity of this type in this tissue, which apparently
      could be influenced by the intensity of a physical stimulus such as sound.
      Finally, an adequate ionic environment appears to play a potential role in the
      expression of the changes observed, indicating that it may function according to
      the requirements of the biological sensor.

PMID- 8543580
TI  - Determination of the protein components of native thin filaments isolated from
      natural actomyosin: nebulin and alpha-actinin are associated with actin
      filaments.
AB  - A new method was developed for extracting natural actomyosin with full length
      connectin (titin) and nebulin from rabbit skeletal muscle. To determine the
      protein components of native thin filaments, thin filaments were isolated from
      natural actomyosin by sedimentation in a H2O/D2O/sucrose density gradient. Both
      alpha-actinin and nebulin were cosedimented with actin filaments, while connectin
      was not. This shows that the native thin filaments contained alpha-actinin and
      nebulin. This indicates that the native thin filaments were more complicated than
      synthetic filaments reconstituted from actin, tropomyosin, and troponin. It is
      known that synthetic filaments are less Ca2+ sensitive than native thin
      filaments. This difference in Ca2+ sensitivity may be due to the differences in
      components and/or the different structures of native and synthetic filaments. The
      newly developed methods described here for extracting natural actomyosin and for
      isolating native thin filaments are useful for addressing these important
      problems related to the structure and function of native thin filaments.

PMID- 8543581
TI  - Evidence for involvement of a 12-residue peptide segment of the heavy chain in
      the neck region of smooth muscle myosin in formation of the 10S conformation.
AB  - Two synthetic peptides having amino acid sequences of the heavy chain segments in
      the neck region of porcine aorta smooth muscle myosin were used to study the
      formation of the 10S folded conformation. These peptides, MHC821-835 and MHC835
      846, correspond to residues 821-835 and 835-846, respectively, of the chicken
      gizzard myosin heavy chain. The effects of these peptides on the filament
      formation of porcine aorta smooth muscle myosin were examined. The filamentous
      myosin fraction increased on the addition of MHC835-846 at NaCl concentrations
      lower than 0.25 M for both dephosphorylated and phosphorylated myosin, while the
      filament formation of dephosphorylated myosin was unaffected by the addition of
      MHC821-835 up to 30 microM. The filaments formed in the presence of MHC835-846
      were observed by electron microscopy to be morphologically indistinguishable from
      those formed in the absence of the peptide. Rotary shadowed images of
      dephosphorylated myosin monomers revealed mostly the 10S form in the absence of
      MHC835-846, while the 6S form was predominant in the presence of the peptide. The
      results indicate that MHC835-846 inhibits the formation of the 10S conformation.
      On cosedimentation assaying with myosin, rod and light meromyosin, MHC835-846
      bound to each of them with a stoichiometry of nearly 1 mol/mol heavy chain.
      Altogether, these results suggest that the region in the myosin heavy chain
      corresponding to MHC835-846 may be involved in the binding site for the light
      meromyosin portion of myosin for formation of the 10S conformation.

PMID- 8543582
TI  - Efficient replication of polyomavirus DNA in a cell-free system supplemented with
      Escherichia coli single-stranded DNA binding protein, which exhibits species
      specificity in the requirement for DNA polymerase alpha-primase.
AB  - We established a modified cell-free system for polyomavirus (PyV) DNA
      replication, which was supplemented with Escherichia coli single-stranded DNA
      binding protein (SSB). DNA synthesis in this system was enhanced by 1.4- to over
      15-fold depending upon the amount of cell extracts contained in the reaction
      mixture. By supplementing with E. coli SSB, we were able to reduce the amount of
      cell extracts in the reaction mixture, and to lower the concentrations of
      creatine phosphate and Tris, rendering this system more resistant to salts than
      the conventional PyV DNA replication system. The modified system was
      characterized using mutant cell extracts which had heat-inactivated DNA
      polymerase alpha. DNA synthesis in the system was dependent on PyV T antigen, the
      PyV origin of DNA replication, mutant cell extracts, and DNA polymerase alpha
      primase complex purified from wild-type cells. The DNA polymerase alpha-primase
      complex was not replaced by DNA polymerase alpha, indicating that this system
      requires a functional DNA polymerase alpha-primase complex. This system exhibited
      species-specificity in the requirement for DNA polymerase alpha-primase; only
      mouse DNA polymerase alpha-primase but not human DNA polymerase alpha-primase
      functioned in this system.

PMID- 8543583
TI  - Activation of phospholipase A2 and acylation of lysophospholipids: the major
      regulators for platelet activating factor production in rat neutrophils.
AB  - Rat inflammatory neutrophils induced arachidonic acid release and platelet
      activating factor (PAF) production in response to opsonized zymosan (OPZ) dose
      dependently. Phospholipase A2 activity also increased dose-dependently,
      paralleling the increases in arachidonic acid and PAF. The time courses of the
      activities of phospholipase A2 and acetyltransferase, and the amounts of free
      arachidonic acid, lyso-PAF, and PAF demonstrated that activation of the enzymes
      in the remodeling pathway could be required for PAF production in rat
      neutrophils, which agrees with the documented fact for macrophages. Phospholipase
      A2 could be a rate-limiting enzyme for PAF production, since an increased lyso
      PAF amount or addition of exogenous lyso-PAF reflected the increase in PAF
      formation in the cells. This phospholipase A2 activity in rat neutrophils could
      be attributed to cytosolic type phospholipase A2, because the activity was mostly
      suppressed by a specific antibody to cytosolic phospholipase A2. As previously
      reported, pretreatment of neutrophils with the acyl-CoA synthetase inhibitor,
      triacsin C, or the acyltransferase inhibitor, merthiolate, enhanced PAF
      production as well as arachidonic acid release by the cells in response to OPZ.
      Triacsin C inhibited arachidonoyl-CoA production and merthiolate suppressed the
      transacylation of lyso-PAF to 1-alkyl-2-arachidonoyl-GPC. These results suggest
      that these inhibitors of acylation of lyso-PAF caused accumulation of lyso-PAF,
      which resulted in enhancement of PAF production when phospholipase A2 and
      acetyltransferase were activated by OPZ. Thus the activation of cytosolic
      phospholipase A2 and the acylation of lyso-PAF by such as arachidonic acid could
      be regulating factors for PAF production in stimulated rat neutrophils.

PMID- 8543584
TI  - Expression of calcitonin receptors on human myeloid leukemia cells.
AB  - Certain osteoclastic markers (multinucleation and tartrate-resistant acid
      phosphatase) were induced in human leukemia HL-60 cells by treatment with 10(-7)
      M 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] for 10 days. However, no formation of
      pits on a bone substrate by vitamin-treated HL-60 cells was detected. Expression
      of calcitonin receptors (CTR), another osteoclastic marker, was examined by means
      of the reverse transcriptase polymerase chain reaction. The human CTR-cDNA (T47D
      isotype) was amplified from untreated HL-60 cells, but not from cells treated
      with 1,25(OH)2D3. The CTR mRNA disappeared within 24 h after the treatment. Thus,
      1,25(OH)2D3-differentiated HL-60 cells failed to show two intrinsic
      characteristics of osteoclasts, pit formation on a bone substrate and expression
      of CTR. We then examined the expression of CTR on established human leukemia cell
      lines. The CTR mRNA was expressed in myeloblastic ML-1 and promyelocytic HL-60
      leukemia cells but not in more mature macrophage-like cell lines, U-937 and THP-1
      cells. Neither B cell leukemia BALL-1, T cell leukemia Jurkat,
      promegakaryoblastic leukemia Meg-J, nor cervix uteri carcinoma HeLa S3 cells
      amplified the CTR products. The cDNA of BIN67-isotype CTR, that has an additional
      16-amino acid insert in the putative first intracellular loop of T47D-type CTR
      [Kuestner et al. (1994) Mol. Pharmacol. 46, 246-255], was amplified by neither
      strain tested. It was suggested that the T47D-type CTR is a novel differentiation
      antigen of immature myeloid lineage cells.

PMID- 8543585
TI  - Purification and phosphorylation of a M(r) 25,000 protein, an effective phosphate
      acceptor for casein kinase II and protein kinase C, detected in the cytosolic
      fraction of Xenopus laevis oocytes.
AB  - A common and effective phosphate acceptor protein for casein kinase II and Ca(2+)
      phospholipid-dependent protein kinase (protein kinase C) was purified to near
      homogeneity from the cytosolic fraction of Xenopus laevis oocytes. Its molecular
      mass was estimated to be approximately 25,000 by SDS-polyacrylamide slab gel
      electrophoresis and gel filtration analyses. About 1 and 2 mol of phosphate were
      incorporated per mol of this protein with casein kinase II and protein kinase C,
      respectively, and the phosphorylated amino acid was identified as serine
      irrespective of the protein kinase employed. The Km values were calculated to be
      1 and 0.5 microM for this M(r) 25,000 protein with casein kinase II and protein
      kinase C, respectively. However, this protein was a relatively poor substrate for
      casein kinase I and did not serve as one for cAMP-dependent protein kinase. The
      amino acid sequence of its amino-terminal region suggests that this protein is a
      newly identified substrate for these two protein serine/threonine kinases.

PMID- 8543586
TI  - Regional chemotherapy: revisited.

PMID- 8543587
TI  - Relation of oestradiol-mediated growth stimulation with the expression of c-erbB
      2 protein in xenotransplanted oestradiol-receptor-positive and -negative breast
      carcinomas.
AB  - Attempts were made to correlate growth effects induced by oestradiol and
      tamoxifen with the hormonal regulation of c-erbB-2 protein in experiments in
      vivo. We report here the responsiveness of four xenotransplanted oestrogen
      receptor(ER)-positive and four ER-negative human mammary carcinomas to oestradiol
      and tamoxifen. Oestradiol in a dose of 0.5 mg/kg significantly increased the
      growth of the ER-positive mammary carcinomas 3366, MCF-7, 4134 and 4049, but not
      the ER-negative tumours 4000, 4296 and MT-3. However, within the group of the ER
      negative breast carcinomas the tumour 4151 ES deviates from this growth
      behaviour, as we could prove an estrogen induced growth. The stimulation of
      tumour growth by oestradiol was always accompanied by a down-regulation of c-erbB
      2 protein both in the ER-positive mammary carcinomas and in the ER-negative
      mammary carcinoma 4151 ES. Tamoxifen significantly inhibited the growth of the
      ER/PR-positive mammary carcinomas 3366 and MCF-7 but not the ER-positive/PR
      negative mammary carcinomas 4049 and 4134. In the group of ER-negative mammary
      carcinomas only the growth of the oestrogen-responsive tumour 4151 ES was
      significantly inhibited by tamoxifen. The inhibition of tumour growth by
      tamoxifen was correlated with a reversion of the oestradiol-induced down
      regulation of c-erbB-2, also in the ER-negative/oestradiol-responsive mammary
      carcinoma 4151 ES. From our results we hypothesize that the oestrogen-dependent
      growth of ER-negative breast carcinoma 4151 ES could also be correlated with the
      oestradiol-regulated expression of c-erbB-2 protein.

PMID- 8543588
TI  - Modulation of sensitivity to mitomycin C and a dithiol analogue by tempol in non
      small-cell lung cancer cell lines under hypoxia.
AB  - We examined the mechanisms involved in the bioactivation of mitomycin C (MMC) and
      a newly developed MMC analogue: 7-N-(2-([2-(gamma-L
      glutamylamino)ethyl]dithio)ethyl)mitomycin C, KW-2149, in non-small-cell lung
      cancer (NSCLC) cell lines under aerobic and hypoxic conditions. To investigate
      these mechanisms, we used MMC-resistant non-small-cell lung cancer cell lines (PC
      9/MC4) that had been established in our laboratory from the parent PC-9 cell line
      by continuous exposure to MMC. We previously reported that the MMC-resistant cell
      line (PC-9/MC4) was poor in NAD(P)H dehydrogenase (quinone) activity and
      approximately 6-fold more resistant than the parent cells (PC-9) to MMC on 2-h
      exposure under aerobic conditions. In this study, the subline PC-9/MC4 was 6.7
      fold more resistant to MMC than PC-9, the parent cell line, under aerobic
      conditions, and 5.2-fold more resistant under hypoxic conditions after 2-h
      exposure to MMC. However, on co-incubation with tempol, an inhibitor of the one
      electron reduction pathway, the sensitivity of PC-9/MC4 to MMC was impaired under
      hypoxic conditions, but the impairment was not evident under aerobic conditions.
      KW-2149, the newly developed MMC analogue, was cytotoxic for both PC-9/MC4 and PC
      9 cells, and the sensitivity of both cell lines to KW-2149 was not changed by
      exposure to hypoxic conditions or by coincubation with tempol. There were no
      significant differences in the intracellular uptake of MMC and the activities of
      cytosolic detoxification enzymes between the PC-9 and PC-9/MC4 cell lines. These
      results support the hypothesis that the one-electron reduction pathway plays a
      partial role in the bioactivation of MMC, but not of KW-2149, and that KW-2149 is
      excellent at circumventing resistance to MMC in NSCLC.

PMID- 8543589
TI  - Membrane interactions of some catamphiphilic drugs and relation to their
      multidrug-resistance-reversing ability.
AB  - The multidrug-resistance (MDR)-reversing ability of the catamphiphilic drugs
      could be mediated through their interaction with the membrane phospholipids. This
      could lead directly (through changes in membrane permeability and fluidity)
      and/or indirectly (through inhibition of P-glycoprotein phosphorylation via
      inhibition of the phosphatidylserine-dependent protein kinase C or changes in the
      conformation and functioning of the membrane-integrated proteins via changes in
      the structure organization of the surrounding membrane bilayer) to the reversal
      of MDR. Using differential scanning calorimetry and NMR techniques and artificial
      membranes composed of phosphatidylcholine or phosphatidylserines we found a
      significant correlation between the MDR-reversing activity of the drugs in
      doxorubicin-resistant human breast carcinoma MCF-7/DOX and murine leukaemia
      P388/DOX tumour cells (data taken from the literature) and their ability to
      interact with phosphatidylserines. Trans- and cis-flupentixol were found to
      interact most strongly with both the phospholipids, followed by trifluoperazine,
      chlorpromazine, triflupromazine, flunarizine, imipramine, quinacrine and
      lidocaine. Differences in the interaction of trans- and cis-flupentixol with the
      phospholipids studied are suggested to be responsible for their different MDR
      reversing ability. Verapamil showed moderate membrane activity, assuming that the
      membrane interactions are not the only reason for its high MDR-reversing ability.
      Amiodarone showed very strong interactions with phosphatidylserines and is
      recommended for further MDR-reversal studies.

PMID- 8543591
TI  - Promotive action of acylated ascorbate on cellular DNA synthesis and growth at
      low doses in contrast to inhibitory action at high doses or upon combination with
      hyperthermia.
AB  - Effects of 6-O-palmitoyl ascorbate (ascorbate) developed to increase the
      antitumour activity of ascorbic acid on DNA synthesis and proliferation of
      Ehrlich ascites tumour cells were investigated. Treatment of the cells with the
      acylated ascorbate at 25-50 microM for 1 h resulted in no effect on DNA
      synthesis, assayed by pulse incorporation of [3H]thymidine after a culture period
      of 20 h, but led to 49%-87% enhanced DNA synthesis after 4 days, suggesting that
      long-term culture is required for promotion by ascorbate to occur. At a dose as
      high as 75 microM acylated ascorbate, however, cellular DNA synthesis was 64%
      inhibited after 20 h and 99% after 4 days. The results suggest that acylated
      ascorbate exhibits a dual action on DNA synthesis: promotion at low doses and
      inhibition at high doses, both of which are potentiated in a time-dependent
      manner. In contrast to the above-mentioned results at 37 degrees C, acylated
      ascorbate at 25-75 microM inhibited but did not promote DNA synthesis at 42
      degrees C whatever the culture period. Similar results were exhibited when
      proliferation of cells cultured for a long period was investigated. At 37 degrees
      C, 50 microM acylated ascorbate increased the number of the cells to 3.6 times
      the control values after 8 days and to 1.9 times after 11 days; in contrast, a 75
      microM dose decreased the cell number considerably. Combination with hyperthermia
      (42 degrees C) suppressed the increase and cell growth was completely inhibited
      at 75 microM.

PMID- 8543592
TI  - Biodistribution in tumour-bearing mice of polycationic, amphoteric and
      polyanionic branched polypeptides with a poly(L-lysine) backbone labelled with
      125I and 111In: tumour accumulation less than that of labelled serum proteins.
AB  - The biodistribution has been studied in mice with subcutaneously transplanted
      solid tumours (mammary carcinoma and melanoma) of synthetic branched-chain
      polypeptides based on poly(L-lysine). The polypeptides were a poly(L-lysine)
      backbone with side-chains of three DL-alanine residues (AK, which is
      polycationic), AK with additional glutamic acid residues at the end of the side
      chains (EAK, which is amphoteric) and EAK in which the terminal glutamic acid
      amino groups had been acetylated (AcEAK, which is polyanionic) or succinylated
      (SucEAK, which is highly polyanionic). Polypeptides were labelled with 125I by
      reaction with Bolton and Hunter reagent, or with 111In by chelation to
      diethylenetriaminepentaacetic acid previously conjugated to them. As controls,
      natural plasma proteins (immunoglobulin G, albumin and transferrin) were
      similarly labelled. Over a study period of up to 7 days, even with the
      polypeptides showing most prolonged blood survival (EAK and AcEAK) there was no
      particular uptake or retention in tumour tissue, over and above what was seen
      with control plasma proteins and/or in normal tissues. Overall these findings
      suggest that any enhanced permeability and retention in tumour tissue, reported
      by other workers with other synthetic macromolecules, operates poorly with the
      present polypeptides and/or tumours. Specific tumour targeting, for example with
      monoclonal antibodies, would seem a better option than non-specific accumulation
      of macromolecules.

PMID- 8543590
TI  - Roots and perspectives of contemporary papillomavirus research.

PMID- 8543594
TI  - Long-term results of surgery for small primary liver cancer in 514 adults.
AB  - During 1958-1993, 2030 patients with pathologically proven primary liver cancer
      (PLC) were retrospectively reviewed. Comparison between small PLC (< or = 5 cm, n
      = 514) and large PLC (> 5 cm, n = 1516) revealed that small PLC had a higher
      resection rate (92.4% versus 49.1%), lower operative mortality (1.7% versus
      5.2%), a higher percentage of single tumour nodules (78.0% versus 53.4%), a
      higher percentage of well encapsulated tumour (74.5% versus 35.8%) and higher
      survival rates after resection (5-year, 63.8% versus 36.6%; 10-year, 46.8% versus
      28.5%). No significant difference was found between survival following limited
      resection (n = 440) and lobectomy (n = 34) in patients with small PLC. Re
      resection of any subclinical recurrence or solitary pulmonary metastasis after
      small PLC resection was done in 70 cases. These results indicate that resection
      is still the modality of choice for treatment of small PLC; limited resection
      instead of lobectomy was the key to increasing resectability and decreasing
      operative mortality; re-resection of subclinical recurrence was important to
      prolong survival further.

PMID- 8543593
TI  - mRNA levels of nm23 in murine ascites hepatoma (H22) clones with different
      lymphatic metastatic potential.
AB  - Levels of expression of the nm23 gene inversely correlated with metastatic
      potential in several rodent tumor model systems and human breast carcinoma. In
      the present study, we examined nm23 mRNA levels in two murine ascites hepatoma
      models (H22-16A3-F and H22-A2-P) with different metastatic potentials. Metastatic
      H22-16A3-F (80% metastatic rate) and non-metastatic H22-A2-P clones were both
      derived from murine ascites hepatoma (H22). We found that a 0.8-kb nm23
      transcript was expressed in both cell clones. The nm23 gene was expressed at a
      higher level in non-metastatic H22-A2-P: approximately 8.6-fold higher than in
      metastatic H22-16A3-F. The present data suggest that the expression of nm23 mRNA
      might be associated with metastasis of murine ascites hepatoma (H22), though
      heterogeneity of nm23 steady-state expression levels among the H22 clones remains
      to be investigated.

PMID- 8543595
TI  - Adjuvant carboplatin treatment for seminoma clinical stage I.
AB  - The traditional adjuvant therapy for seminoma stage I is abdominal radiotherapy.
      Although the relapse rate ranges below 5% this treatment is challenged because
      concerns about adverse late effects are accumulating. Carboplatin is effective in
      metastatic seminoma and two pilot studies have indicated effectivity in the
      adjuvant setting also. As this drug is almost non-toxic in moderate doses it
      could be an ideal adjuvant treatment for seminoma stage I. A group of 82
      patients, mean age 37.5 years (range 22-73 years), with histologically pure
      seminoma stage I, were given carboplatin 400 mg/m2 after orchiectomy; 60 patients
      received only one course of carboplatin, and 22 patients received two courses.
      The median time of observation is 24 months, ranging from 2 to 48 months, and 66
      patients have a minimum follow-up of 1 year. There is one relapse so far.
      Toxicity is rather mild with no severe nausea/emesis. Mean platelet counts were
      164/nl after 3 weeks and 208/nl after 4 weeks; thus, myelotoxicity was
      negligible. Gonadal toxicity was measured by serial follicle-stimulating hormone
      levels. The mean level was 11.4 U/l before treatment, and 16.2 U/l after 5 weeks,
      17.3 U/l after 4 months, 14.5 U/l after 8 months and 13.5 U/l after 12 months.
      Thus, gonadal toxicity also appeared to be mild. In summary, the efficacies of
      adjuvant carboplatin and of abdominal radiotherapy seem to be identical. As
      carboplatin, in the dosage used, involves no severe acute side-effects and
      probably few late adverse effects, this regimen constitutes a promising new
      treatment option in seminoma patients stage I that deserves to be studied in
      randomized trials.

PMID- 8543596
TI  - A method to perfuse liver metastases with heated blood (45 degrees C, 45 min).
AB  - To heat the livers in ten pigs (20-30 kg) a system of two pumps, both connected
      to the cannulated A.femoralis and to two radio-wave heating devices, was used.
      With pump I the arterial vascular system of the liver was perfused for 45 min via
      the A.gastroduodenalis with a constant volume of 150-200 ml blood/min, heated to
      44-45 degrees C. With pump II 50-700 ml/min heated blood was pumped into the
      portal vein to raise the temperature and oxygen content of the portal flow.
      During the heating period the A.hepatica was clamped. A temperature of 45 degrees
      C is a highly toxic for the differentiated liver tissue, but the more simply
      structured wall of the arteries tolerates this temperature. This difference in
      heat resistance allows the perfusion of the arterial vascular system of the liver
      with blood heated to a temperature that is fatal to liver tissues. On the way
      from the A.gastroduodenalis to the liver periphery the heated blood becomes
      cooled by the surrounding cooler liver tissues. Finally the supply to the lobules
      is a mixture of arterial and venous blood, i.e. the highly toxic agent, heat,
      becomes "detoxified" by cooling before reaching the heat-sensitive liver lobules.
      Changing flow and temperature in the portal vein allows the temperature of the
      liver lobules to be kept within a safe range, i.e. below 43 degrees C. The raised
      oxygen content in the portal flow allows the arterial perfusion to be stopped for
      10 min (to subject a heated metastasis to a period of hypoxia). Liver enzymes
      reached their maximal level 2 days after heating and returned to normal within 1
      week. It is supposed that this method allows the temperature in a liver
      metastasis to be raised to a tumoricidal level.

PMID- 8543598
TI  - Hip.

PMID- 8543597
TI  - The changing role of ultrasound in the management of developmental dysplasia of
      the hip (DDH)

PMID- 8543599
TI  - Dynamic ultrasound assessment for monitoring of treatment of congenital
      dislocation of the hip.
AB  - Of the 7,827 babies born in Sheffield between March 1989 and August 1991, a total
      of 114 (1.4%) who had either clinical abnormality of the hip or high-risk factors
      for congenital dislocation of the hip (CDH) were examined by ultrasound at birth
      and at regular intervals. Dynamic ultrasound assessment of both hips was done to
      diagnose instability and to monitor the treatment. Abnormal findings were
      recorded in 55 babies at the first visit, and 31 of these subsequently required
      treatment with the Pavlik harness (3.9 per 1,000). Only one case of late CDH has
      been seen among the babies who were not examined by ultrasound. There were no
      cases of avascular necrosis in our series. Dynamic ultrasound examination of high
      risk infants' hips is a reliable method of screening for CDH. Monitoring of hips
      treated with the Pavlik harness, by dynamic ultrasound examination, can identify
      failure to obtain a concentric reduction, and in such cases, splintage can be
      abandoned in favour of other modes of treatment. It can, therefore, reduce the
      chances of overtreatment and its associated complications.

PMID- 8543600
TI  - The Pavlik harness and developmental dysplasia of the hip: has ultrasound changed
      treatment patterns?
AB  - Monitoring Pavlik harness therapy for developmental dysplasia of the hip (DDH)
      has been used at our institution since 1986. In this study, we compared Pavlik
      therapy for DDH without ultrasound monitoring (group A) to similar therapy with
      ultrasound monitoring (group B). Both groups had similar age at diagnosis.
      Treatment failure was recognized earlier in group B than in group A (4.9 vs. 9.3
      weeks). The total number of radiographs was significantly decreased in group B.
      The duration of therapy was less in group B than in group A. Successfully treated
      hips had an average increase in alpha angle of 8.4 degrees per month. The average
      failure rate in hips resting in a dislocated position at the onset of Pavlik
      therapy was unchanged by Pavlik monitoring.

PMID- 8543601
TI  - Neonatal hip instability: normal values for physiological movement of the femoral
      head determined by an anterior-dynamic ultrasound method.
AB  - A total of 910 clinically normal hips in neonates younger than 48 h old was
      examined using an anterior-dynamic ultrasound method to determine normal values
      for the femoral head diameter and physiological movement of the femoral head in
      relation to the acetabulum. The femoral head diameters were found to correlate
      positively with both birthweight and gestational age and to be larger in boys
      than in girls, the mean values being 16.08 +/- 1.49 mm and 15.56 +/- 1.43,
      respectively. The values for maximal movement of the femoral head in relation to
      the acetabulum at provocation by Palmen/Barlow's test were 6.0, 6.6, and 6.8 mm
      for the birthweights 2,000, 3,000, and 4,000 g, respectively. No significant
      difference was found between the results of four independent observers in the
      femoral head movement at provocation. The results of the first and the fourth
      examination were not significantly different, suggesting that more than four
      examinations are required to induce hip instability by using the Palmen/Barlow
      test. Repeated examination after 4 h did not show any significant difference
      between examinations.

PMID- 8543602
TI  - Ultrasonography in the management of developmental dysplasia of the hip (DDH).
AB  - Real time ultrasonography, according to the method of Graf, was performed on 113
      infant hips because of abnormal physical findings (ranging from hip clicks to
      frank dislocation). Three parameters were measured on the standard coronal
      images: alpha and beta angles of Graf and the d/D ratio of Morin. Results
      indicated that the presence of hip clicks (88 hips) in general is a benign
      condition and not associated with abnormal anatomy. Hips that were reduced at
      birth but dislocatable (Barlow hip) showed no significantly abnormal acetabular
      anatomy. Hips that were dislocated at rest but were reducible (Ortolani hip)
      showed definite abnormal acetabular anatomy and femoral head coverage.
      Ultrasonography is beneficial in the management of developmental dysplasia of the
      hip (DDH); it confirms the clinical findings and eliminates radiation exposure to
      the infant's pelvis, especially in the first 4-6 months of life when standard
      radiography is not always reliable in diagnosing DDH.

PMID- 8543603
TI  - Long-term results of congenital dislocation of the hip treated with the Pavlik
      harness.
AB  - We present the radiographic and clinical results of 158 hips (127 congenital
      dislocations of the hip, 31 acetabular dysplasias) that were followed-up for > 20
      years after the application of the Pavlik harness. The mean Sharp angle of these
      hips was larger than that of the normal Japanese hip, and the mean center-edge
      angle was smaller. Thirty hips (19%) were classified as class III, according to
      Severin's classification. Of 48 unaffected hips in the unilateral cases, 15 hips
      (31%) had steep acetabula. We believe an intrinsic factor disturbs the normal
      development of acetabular cartilage in both hips of the patients. Thirty-five
      hips (22.2%) showed variable grades of deformity of the femoral head, neck, or
      both. Clinically, most of the treated hips were good in the 3rd decade.

PMID- 8543604
TI  - Radiologic pelvic asymmetry in unilateral late-diagnosed developmental dysplasia
      of the hip.
AB  - Eighty-three cases of unilateral late-diagnosed (older than 4 months of age)
      developmental dysplasia of the hip (DDH) were studied to evaluate pelvic shape
      and innominate bone relationships in the initial anteroposterior radiograph. To
      be included, each initial radiograph had to have no lumbar pedicle rotation,
      lumbar scoliosis, gas shadows, or metallic protectors. Measurements were done
      using as reference a medial pelvic line, which divides the pelvis into two
      innominate bones. Lineal parameters were defined to assess pelvic radiologic
      shape; angular parameters defined the relationship between the ilium, ischium and
      pubis, and sacrum. Statistically significant differences were observed in most
      cases, and pelvis asymmetry was evident. The asymmetry was more obvious in cases
      in which the teardrop had a negative value and in low dislocations. Similar
      changes have been observed in experimental dislocation of the hip secondary to a
      triplane pelvic deformity. We suggest that similar alterations of pelvic shape
      occur in DDH, possibly secondary to growth disturbance in the triradiate
      cartilage.

PMID- 8543605
TI  - Closed reduction of developmental dislocation of the hip in children older than
      18 months.
AB  - Thirty-eight hips in 32 patients > or = 18 months of age had closed reduction
      attempted for developmental dislocation of the hip. Twenty-six hips in 24
      patients had an initially successful closed reduction. During cast treatment
      three of 26 hips had progressive subluxation or dislocation requiring open
      reduction with or without concomitant osteotomies. The remaining 23 hips, with an
      average follow-up of 8 + 8 years, are thought to have had a successful closed
      reduction. Eleven of those hips have required no further surgical procedures and
      had an average acetabular index of 18 degrees at last follow-up. Twelve of the 23
      hips that had successful closed reduction required a femoral or pelvic osteotomy
      for failure to remodel. Younger age (< 22 months) at the time of reduction and
      lower grade (I and II) dislocation were favorable prognostic indicators of the
      likelihood of successful closed reduction.

PMID- 8543606
TI  - Derotational femoral shortening for developmental dislocation of the hip: special
      indications and results in the child younger than 2 years.
AB  - Combining derotational femoral shortening osteotomy with open reduction to reduce
      the incidence of redislocation and avascular necrosis (AVN) in developmental
      dislocation of the hip (DDH) was first used only for older children. In special
      circumstances (teratologic dislocation, syndrome-related DDH, difficult home
      environment), we have combined femoral shortening with open reduction in 15
      children (20 hips) ranging in age from 5 to 23 months old. Fourteen hips required
      concurrent pelvic osteotomy. Complications included partial AVN in two hips,
      residual subluxation requiring acetabular osteotomy in two hips, and residual
      dysplasia in two hips. Radiographic evaluation by the Severin method revealed 15
      good or excellent hips and five hips rated fair or less. Hips reduced without
      pelvic osteotomy produced better radiographic results than those treated with a
      concomitant augmentation acetabuloplasty (Albee). This procedure can injure the
      growth centers of the acetabular rim in a very young child. Derotational femoral
      shortening can be used in special circumstances to achieve reduction in DDH in
      children younger than 2 years. The surgery is technically demanding, and the
      surgeon should have extensive prior experience using this method in older
      children.

PMID- 8543607
TI  - Errors in measurement of acetabular index.
AB  - Errors in determining the acetabular index can be induced either by incorrectly
      positioning the child for radiographs or by inter- or intraobserver errors. From
      postmortem radiographic studies, we have determined the magnitude of these
      errors. The error caused by pelvic rotation is +/- 3 degrees if the obturator
      foramina ratio is kept within 0.5 to 2. If pelvic flexion/extension is confined
      to +/- 10 degrees, the error induced by flexion/extension is +/- 3 degrees. The
      intraobserver error was +/- 2 degrees, and the interobserver error was +/- 3
      degrees. Under these circumstances, the total error is +/- 5 degrees. We have not
      been able to find a satisfactory way of limiting the flexion/extension to +/- 10
      degrees. In some circumstances, particularly if a child is distressed, the
      flexion/extension may be 20 degrees from neutral; under these circumstances,
      errors as large as 10 degrees can occur. Surgeons should be aware that very large
      errors can occur when the acetabular index is measured.

PMID- 8543608
TI  - The subluxating or wandering femoral head in developmental dislocation of the
      hip.
AB  - The subluxating ("wandering") femoral head in developmental dysplasia of the hip
      (DDH) has heretofore not been clearly separated from subluxation. The former is
      passively reducible, whereas the latter is not. The subluxating hip in paralytic
      and other connective disorders is well established, but the author has
      encountered several well-documented cases of this problem in DDH, and four have
      at least a 2-year follow-up. Three important issues are significant in these
      cases. The physical findings can be very elusive in the subluxating hip, the
      radiographic manifestations are different from those encountered in the
      subluxated hip, and effective treatment requires a pelvic osteotomy that alters
      the shape of the acetabulum (Pemberton or Dega). The redirectional (Salter)
      osteotomy does not provide adequate coverage in this situation wherein the
      femoral head/acetabular relations are so unstable. Two examples are presented to
      illustrate these issues.

PMID- 8543609
TI  - Acetabular changes in an experimental model of developmental dysplasia of the hip
      (DDH).
AB  - We wished to correlate the morphological acetabular changes in developmental
      dysplasia of the hip (DDH) with changes at the tissue level. A secondary aim was
      to develop a way of measuring the dysplastic acetabulum. We studied the changes
      in rabbit acetabula after maintaining knee extension, measuring the major
      diameter from the acetabular notch to the farthest opposite point on the
      acetabular margin. The minor diameter was at right angles to this. The dysplastic
      acetabula showed elongation along the major diameter compared to control hips.
      Microscopic sections were made along major and minor diameters. The
      posterosuperior lip of the dysplastic acetabulum showed an early eversion of the
      acetabular cartilage. Growth of the articular cartilage in this new direction
      accounted for the acetabular elongation. As well as providing insight into the
      manner of acetabular shape change, the findings suggest the nature of remodeling
      required before normal acetabular growth can resume during treatment.

PMID- 8543610
TI  - Parallax radiology of the hip.
AB  - We report our use of a simple radiographic technique that uses the principle of
      parallax for evaluating the anterior-posterior relationship of the proximal femur
      to the triradiate cartilage in skeletally immature patients. Thirty-six paired
      plain radiograph parallax views were compared with 13 respective computed
      tomography scans of the hips in seven patients. All had undergone closed or open
      reductions and were in spica casts at the time of radiographic evaluation. The
      parallax views detected all cases of anterior or posterior subluxation or
      dislocation when present. We found this method to be reliable and easily
      performed in the casted patient for use in radiographically evaluating pediatric
      hip subluxation in the anterior-posterior dimension.

PMID- 8543611
TI  - Spherical assessment of the hip on standard AP radiographs: a simple method for
      the measurement of the contact area between acetabulum and femoral head and of
      acetabular orientation.
AB  - A template that allows a simple three-dimensional assessment of the hip joint is
      presented. The total surface of a sphere is subdivided into spherical quadrangles
      and triangles that cover areas of exactly identical size. On the template, these
      quadrangles and triangles are projected onto a plane. Each segment represents
      0.5% of the total surface of the sphere. Calculation of any surface area is
      achieved by adding the number of segments involved of a template of appropriate
      radius. In addition, various angles can be measured. The template is drawn in
      various sizes on transparent foil. The template of the appropriate size is laid
      on the anteroposterior radiograph of the hip joint. It allows measurement of the
      contact area between the acetabulum and the femoral head and also acetabular
      orientation. A cadaver study showed good reliability of the measurements.

PMID- 8543612
TI  - The c/b ratio in the radiological monitoring of the hip joint in congenital
      dislocation of the hip.
AB  - We report a method of monitoring hip joint development for congenital dislocation
      of the hip in children. The c/b ratio was measured on serial radiographs of 41
      hips in 38 patients. The measurement was compared to c/b ratio obtained from
      normal hips. It was used to detect concentric reduction or its loss by migration
      of the femoral head during growth. The age at diagnosis ranged from 8 months to
      10 years 6 months. The normal c/b ratio was found to change little with age.
      Deviation of the c/b ratio from normal in congenital dislocation of the hip
      resulted in a poor outcome and identified cases requiring further surgical
      intervention. This measurement of c/b ratio is simple and accurate, using easily
      determined points. The graphic display promotes critical analysis of situation
      and allows selection of cases at risk for treatment.

PMID- 8543613
TI  - Deformity of the pelvis in developmental dysplasia of the hip: three-dimensional
      evaluation by means of magnetic resonance image.
AB  - Magnetic resonance images of the transverse section of the whole pelvis were
      obtained in eight infants (two boys and six girls) with unilateral developmental
      dysplasia of the hip (DDH), and then a three-dimensional image of the pelvis was
      reconstructed from each slice by using a computerized technique. Based on it, the
      deformity of the pelvis with DDH was analyzed by measuring bony configuration
      from the superoinferior, anteroposterior and lateral views. The prime deformity
      of the pelvis with DDH was not only a simple malrotation but also an increased
      medial twisting of the whole involved pelvic wing. As a result, the entrance of
      the socket rotates more anteriorly because of this distortion, which leads to
      poor anterior acetabular coverage over the femoral head.

PMID- 8543614
TI  - The use of ultrasound in the diagnosis of atypical pathology in the unossified
      skeleton.
AB  - Three cases are presented: a congenital dislocation of the patella, a congenital
      dislocation of the radial head, and an epiphysiolysis of the distal humerus. In
      all three cases the pathology involved unossified parts of the skeleton poorly
      demonstrated by plain radiographs. Ultrasonography proved useful in diagnosis and
      treatment of these cases.

PMID- 8543615
TI  - Hemophilic arthropathy of the elbow.
AB  - We investigated the characteristics of hemophilic arthropathy of the elbow joint
      in 32 patients 5-12 years of age who had been followed-up from infancy.
      Restriction of forearm rotation and elbow extension was the most common finding
      in the joints with recurrent hemarthrosis. Limitation of rotation resulted mainly
      from hypertrophy of the radial head. Advancement of bone age was also commonly
      observed in the joints with hemarthrosis. Mild to moderate hemophilic arthropathy
      was associated with greater advancement of bone age than was severe arthropathy.
      There was a discrepancy between the growth of the intraarticular subchondral
      epiphyseal cartilages and the cartilages of the medial and lateral epicondyles
      (apophyseal cartilage). This differential growth may be an important factor in
      the development of complicated and variable hemophilic elbow deformities.

PMID- 8543616
TI  - Intraoperative wedging of casts: correction of residual angulation after
      manipulation.
AB  - Seventy children, aged 2-14 years, had a manipulation under anaesthetic (MUA) of
      a forearm or lower leg fracture, in which the MUA failed to fully correct the
      deformity in 16. An opening wedge (WEDGE) was performed while still under the
      original anaesthetic in one group and compared to a parallel but uncontrolled
      group using the traditional regimen of remanipulation (RE-MUA). There was an
      observed reduction in the average time under anaesthetic comparing WEDGE to RE
      MUA in the forearms (34 vs. 46 min) and in the legs (42 vs. 61 min). There was no
      obvious difference between the proportion of those needing "further adjustments"
      (defined as wedging at outpatients or a further MUA) if the fracture displaced
      comparing WEDGING (zero of six) to RE-MUA (one of 10), and there was also no
      obvious increased time to union. At review, there was < 10 degrees malunion in
      any plane, which should not predispose to restricted forearm rotation or chronic
      ligamentous strain/joint degeneration in the leg.

PMID- 8543617
TI  - Intraoperative somatosensory evoked potential monitoring in pediatrics.

PMID- 8543618
TI  - Annual Meeting of the Pediatric Orthopaedic Society of North America, Miami,
      Florida, April 30-May 4, 1995.

PMID- 8543619
TI  - Role of re-screening of cervical smears in internal quality control.
AB  - AIMS: To investigate the use of rapid re-screening as a quality control method
      for previously screened cervical slides; to compare this method with 10% random
      re-screening and clinically indicated double screening. METHODS: Between June
      1990 and December 1994, 117,890 negative smears were subjected to rapid re
      screening. RESULTS: This study shows that rapid re-screening detects far greater
      numbers of false negative cases when compared with both 10% random re-screening
      and clinically indicated double screening, with no additional demand on human
      resources. The technique also identifies variation in the performance of
      screening personnel as an additional benefit. CONCLUSION: Rapid re-screening is
      an effective method of quality control. Although less sensitive, rapid re
      screening should replace 10% random re-screening and selected re-screening as
      greater numbers of false negative results are detected while consuming less
      resources.

PMID- 8543620
TI  - Flow cytometry in diagnosis and management of large fetomaternal haemorrhage.
AB  - AIMS: To evaluate an indirect immunofluorescence flow cytometry technique in a
      series of patients with large fetomaternal haemorrhage (FMH). METHODS: Patient
      samples identified by Kleihauer testing in local laboratories as having FMH > 4
      ml were sent for flow cytometric analysis. In a proportion of cases the mothers
      received anti-D immunoglobulin prophylaxis according to the flow cytometer
      estimate of FMH volume. RESULTS: Forty three cases of FMH were studied
      prospectively. The correlation between Kleihauer and flow cytometry results was
      poor. In 38 (88%) cases the size of FMH quantitated by flow cytometry was lower
      than that estimated using the Kleihauer technique. In 13 (30%) cases no Rh D
      immunoglobulin positive cells were detected by flow cytometry. Centralised review
      of the original Kleihauer films using a calibrated microscope resulted in
      improved, but still suboptimal correlation with flow cytometry results. In 15
      cases anti-D immunoglobulin was given according to the flow cytometer estimation
      of FMH size, resulting in a 58% reduction in the amount of anti-D immunoglobulin
      given. None of the patients were immunised when tested six months later.
      CONCLUSIONS: Flow cytometry is helpful for the accurate quantitation and
      management of patients with large FMH and in cases where the presence of maternal
      haemoglobin F containing cells renders the Kleihauer technique inaccurate.
      Worthwhile reductions in the use of anti-D immunoglobulin can be achieved.

PMID- 8543621
TI  - Tissue diagnosis of intestinal microsporidiosis using a fluorescent stain with
      Uvitex 2B.
AB  - AIMS: To detect intestinal microsporidiosis in paraffin wax embedded biopsy
      specimens using a fluorescence technique incorporating optical brighteners.
      METHODS: Eight HIV infected patients with confirmed intestinal microsporidiosis
      (six with Enterocytozoon bieneusi, one with Encephalitozoon intestinalis and one
      with Encephalitozoon cuniculi infection) and 10 without infection were studied.
      Tissue sections of paraffin wax embedded duodenal biopsy specimens were stained
      with 1% Uvitex 2B, coded and analysed independently by two investigators.
      RESULTS: In all eight cases with confirmed intestinal microsporidian infection,
      spores could be detected easily in tissue sections using the fluorescence
      technique. Spores or other elements consistent with microsporidiosis were not
      found in the 10 patients without infection. CONCLUSION: Staining of tissue
      sections from paraffin wax embedded intestinal biopsy specimens with stains
      incorporating Uvitex 2B is a rapid and easy technique for the diagnosis of
      intestinal microsporidiosis.

PMID- 8543622
TI  - Immunostaining for CD31 and CD34 in Kaposi sarcoma.
AB  - AIMS: To evaluate antibodies directed against CD31 (JC70/A) and CD34 (QBEND/10
      and anti-HPCA-1) more extensively in Kaposi sarcoma; to assess their value in
      routine diagnosis; and to compare them with the traditional endothelial cell
      markers Ulex europaeus agglutinin 1 (UEA-1) and factor VIII related antigen.
      METHODS: Twenty four cases of Kaposi sarcoma were studied retrospectively. All
      specimens had been fixed in formalin and embedded in paraffin wax. The antibodies
      were applied using the Streptavidin biotin technique in all cases except for UEA
      1, for which an indirect two stage method was used involving peroxidase
      conjugated anti-ulex as the secondary antibody. RESULTS: Tumours were classified
      into those showing angiomatoid or lymphangiomatoid elements and spindle cell
      lesions. Universal labelling of all lesions and virtually all elements within
      lesions was seen with the anti-CD34 antibodies QBEND/10 and HPCA-1. Labelling of
      spindle cells was less consistent with JC70/A but both markers were superior to
      the traditional endothelial cell markers UEA-1 and factor VIII related antigen.
      CONCLUSIONS: These data confirm that Kaposi sarcoma is a tumour of endothelial
      cell origin. They shed further light on the histogenesis of this complex tumour
      and demonstrate that immunostaining for CD34 and CD31 can be used as an aid to
      diagnosis in routinely processed tissue.

PMID- 8543623
TI  - In situ end-labelling, light microscopic assessment and ultrastructure of
      apoptosis in lung carcinoma.
AB  - AIMS: To compare in situ end-labelling (ISEL) of apoptosis in lung carcinoma with
      quantitative and semiquantitative light microscopic assessment and
      ultrastructural observations. METHODS: ISEL of apoptosis was evaluated in 42 lung
      carcinomas (24 squamous cell carcinomas, 12 adenocarcinomas and six small cell
      carcinomas). Results were correlated semiquantitatively with the extent of
      apoptosis in haematoxylin and eosin stained sections, with apoptotic indices and
      with ultrastructural observations (nine cases). RESULTS: In each tumour type the
      extent of apoptosis identified by ISEL correlated with that observed on light and
      electron microscopy. Tumour cells undergoing apoptosis showed either uniform
      nuclear staining with a surrounding "halo" or peripheral nuclear membrane
      staining. The latter pattern was more prominent in small cell carcinoma and
      correlated ultrastructurally with early apoptosis. A variable proportion of
      apoptotic cells and apoptotic bodies were unlabelled. Necrotic tumour cells were
      weakly stained but were distinguishable from apoptotic cells. CONCLUSIONS: ISEL,
      if used in conjunction with standard methods for investigating apoptosis, is a
      useful adjunct to the investigation of apoptosis in human tumour tissue.

PMID- 8543625
TI  - Specimen slice radiography of cancer in breast conserving excisions.
AB  - AIM: To investigate histologically the power of specimen slice radiography to
      record invasive and in situ carcinoma in breast conserving cancer excisions.
      METHODS: Twenty six cancer excisions were converted into 171 complete tissue
      slices, which were examined radiographically. From these slices, 373 histological
      blocks were processed and histological and radiographic assessments were
      compared. RESULTS: Radiography and histology mapped excision margins and lesions
      in detail. Radiographic prediction of histology was imprecise. Six invasive
      carcinomas were either undetectable by radiology or reached a radiologically
      clear margin. Six small invasive carcinoma satellites were not recognised.
      Adjacent ductal carcinoma in situ was undetectable in nine of 15 cases.
      CONCLUSIONS: Slice radiography and histology are capable of precise lesion
      mapping in breast cancer excisions, and clinical utility of such mapping merits
      investigation. Radiology alone is imprecise and to infer complete excision of
      breast carcinoma by radiography (of excision specimens or residual breast) alone
      may be unsafe.

PMID- 8543624
TI  - Lymphoepithelial carcinoma of the salivary gland: in situ detection of Epstein
      Barr virus.
AB  - AIM: To examine the role of Epstein-Barr virus (EBV) in lymphoepithelial
      carcinoma of the salivary gland in Hong Kong Chinese. METHODS: Ten cases of
      lymphoepithelial carcinoma of the salivary gland (eight parotid and two
      submandibular) were examined. In situ hybridisation was used to localise EBER
      RNA, immunohistochemical methods to detect expression of latent membrane protein
      1 (LMP-1) in EBV positive tumours, and Southern blot analysis to examine the
      clonality of EBV in the two cases where frozen tissue was available. RESULTS:
      None of the cases had a history of Sjogren's syndrome or histological evidence of
      a benign lymphoepithelial lesion. The IgA antibody titre against EBV viral capsid
      antigen was elevated in four cases. All cases were EBV positive by in situ
      hybridisation, with a strong uniform positive signal in the epithelial cells, and
      all cases expressed LMP-1. Southern blot analysis revealed that the clonal
      episomal form of the virus was present. Two of the three female patients in this
      series also developed carcinoma of cervix. One of these carcinomas had
      histological features of a lymphoepithelioma-like carcinoma but was EBV negative.
      CONCLUSIONS: A consistent association between EBV and lymphoepithelial carcinoma
      of the salivary gland was found. The presence of the virus in a clonal episomal
      form, and the expression of LMP-1 viral oncoprotein is further evidence of the
      role of EBV in the oncogenesis of this tumour.

PMID- 8543626
TI  - Vimentin and cytokeratin expression in nodular hyperplasia and carcinoma of the
      prostate.
AB  - AIM: To assess the value of vimentin and cytokeratin (CK) intermediate filament
      proteins (IFPs) in distinguishing between nodular hyperplasia and carcinoma of
      the prostate and in predicting prognosis in prostatic cancer. METHODS: Fifteen
      carcinomas and 49 cases of nodular hyperplasia were studied using frozen sections
      and monoclonal antibodies to CK and vimentin IFPs. RESULTS: There was no
      statistically significant difference in vimentin expression between nodular
      hyperplasia and carcinoma. The luminal epithelium in both also reacted with
      antibodies which detect CK8, 18 and 19. CK 7 expression was found in 57% of cases
      of nodular hyperplasia and was not identified in any carcinoma. There was a
      reaction with antibodies to CK1, 2, 3, 4, 10, 11, and 13 in only a minority of
      cases. There was no statistically significant difference in vimentin and CK
      reactivity in high and low grade carcinomas. CONCLUSION: Neither vimentin nor CK
      expression assists in establishing whether a prostatic lesion is benign or
      malignant or in predicting the biological behaviour of a prostatic carcinoma.

PMID- 8543627
TI  - Immunohistochemistry in apparently normal bone marrow trephine specimens from
      patients with nodal follicular lymphoma.
AB  - AIM: To establish the role of immunohistochemistry (using a limited panel of
      antibodies) in detecting minimal involvement by follicular lymphoma in routinely
      processed bone marrow trephine specimens, which show no obvious morphological
      (light microscopic) evidence of lymphoma; to determine whether bcl-2
      immunostaining in bone marrow distinguishes between benign and malignant
      infiltrates in a patient with nodal follicular lymphoma. METHODS: Twenty seven
      consecutively selected paraffin wax embedded, formalin fixed bone marrow trephine
      specimens were stained with the following antibodies: anti-bcl-2, anti-CD79a,
      anti-CD3, and kappa and lambda light chains, using the Streptavidin biotin
      complex technique. RESULTS: Five of the 27 cases, which showed no evidence of
      involvement by follicular lymphoma on routine stains, showed monotypic B cells on
      immunohistochemistry. Two of the cases were diffuse, while the remaining three
      showed mini-aggregates around bony trabeculae. In all five cases the lymphomatous
      infiltrates were strongly bcl-2 positive. Reactive B lymphoid nodules did not
      show the same degree of bcl-2 positivity, and negative cells could be discerned
      within the reactive nodules. CONCLUSIONS: There is merit in studying so-called
      negative bone marrows immunohistochemically in order to detect minimal
      involvement by follicular lymphoma. A limited panel of antibodies including anti
      bcl-2, anti-CD79a and anti-CD3 is usually adequate to accomplish this. Strongly
      bcl-2 positive lymphoid aggregates in the bone marrow of patients with nodal
      follicular lymphoma are indicative of lymphoma.

PMID- 8543628
TI  - Tissue polypeptide specific antigen for the detection of lymphoproliferative
      diseases induced by cyclosporin.
AB  - AIM: To evaluate the efficacy of tissue polypeptide specific (TPS) antigen for
      the early detection of cyclosporin A (CyA) induced post-transplant
      lymphoproliferative diseases. METHODS: Serum concentrations of TPS antigen were
      analysed using a monoclonal enzyme immunoassay and whole blood CyA concentrations
      were measured using high pressure liquid chromatography. Infection with Epstein
      Barr virus and cytomegalovirus was detected by determining levels of IgM and IgG
      antibodies directed against viral capsid antigen (VCA). Immunohistochemistry and
      analysis of clonality were carried out on formalin fixed, paraffin wax embedded
      tissue. RESULTS: The mean serum concentration of TPS antigen in the eight
      transplant recipients investigated was 60 U/l during periods without complication
      (control), 101 U/l during infection, 166 U/l when the diagnosis of a lymphoma was
      confirmed, and 172 U/l when lymphoma and infection coincided. Increased TPS
      antigen concentrations were detected in six patients one month before detection
      of malignancy. After reduction of immunosuppression and the start of tumour
      regression, TPS antigen concentrations decreased. TPS antigen concentrations
      increased in the one patient who experienced a recurrence. CONCLUSIONS:
      Continuous monitoring of TPS antigen concentrations leads to the early discovery
      of CyA induced lymphoproliferative disease.

PMID- 8543629
TI  - The polymerase chain reaction in the demonstration of monoclonality in T cell
      lymphomas.
AB  - AIMS: To evaluate polymerase chain reaction (PCR) amplification of T cell
      receptor (TCR) beta and gamma chain genes as a means of demonstrating
      monoclonality in T cell lymphomas using histological samples; to compare the
      performance of PCR with Southern blot analysis. METHODS: TCR-beta, TCR-gamma and
      immunoglobulin heavy chain (IGH) genes were analysed using PCR in 55 cases of T
      cell lymphoma (28 frozen tissue and 27 paraffin wax embedded samples), diagnosed
      using morphological and immunohistochemical criteria. The 28 frozen samples were
      subjected to Southern blot analysis using TCR-beta, TCR-gamma and IGH gene
      probes. Twenty five B cell lymphomas and 21 non-neoplastic lymphoid tissue
      samples were used as controls. RESULTS: Using TCR-beta PCR, monoclonality was
      detected in 24 (44%) of 55 T cell lymphomas compared with 43 (78%) of 55 using
      TCR-gamma PCR and in 82% with both techniques. Five (9%) of 55 T cell lymphomas
      were IGH PCR positive. None of the non-neoplastic lymphoid control samples were
      PCR positive. All B cell lymphomas showed a polyclonal pattern with TCR-beta PCR
      while a single B cell lymphoma was positive using TCR-gamma primers. With TCR
      beta PCR, a monoclonal result was seen in 12 (43%) of 28 frozen samples of T cell
      lymphoma, compared with 23 (82%) of 28 using Southern blot analysis. With TCR
      gamma PCR, 19 (68%) of 28 frozen tissue samples were positive, compared with 26
      (93%) of 28 using Southern blot analysis. A single case showed IGH rearrangement
      by Southern blot analysis. CONCLUSION: TCR-gamma PCR should be the method of
      choice for analysis of clonality in paraffin wax embedded sections of
      lymphoproliferative lesions, as TCR-beta PCR has a high false negative rate.
      Southern blot analysis remains the most successful technique when sufficient
      fresh tissue samples and resources are available.

PMID- 8543630
TI  - Changes in cytomorphology of childhood lymphoblastic leukaemia at the time of
      disease relapse. Childhood Leukaemia Working Party of the United Kingdom Medical
      Research Council.
AB  - AIMS: Children in a United Kingdom national trial for relapsed non-B
      lymphoblastic leukaemia (ALL) had their diagnostic and relapse marrow
      cytomorphology compared to see what changes occur during the evolution of the
      disease. METHODS: Each relapse slide was assessed blindly for French American
      British (FAB) type and other morphological features by a panel of three
      independent microscopists without reference to each other or any diagnostic
      material. Diagnostic slides had been assessed by the same panel on an earlier
      occasion. RESULTS: A total of 134 consecutive children was studied. Six (5%) were
      classified as FAB type L2 at diagnosis, compared with 18 (13%) at relapse (a
      difference of 9%). Twenty two (16%) changed their FAB type, 17 (13%) from L1 to
      L2 and five (4%) from L2 to L1. The FAB score fell at relapse in 34 children and
      rose in 14, a difference of 14%. Cell size was the commonest feature to change
      (increasing in 22 and diminishing in nine) followed by prominent nucleoli
      (appearing in 21 and disappearing in six). Forty four (33%) children had
      vacuolated blasts at diagnosis, compared with 48 (36%) at relapse. Twenty five
      changed their vacuole score substantially, 14 gaining > 10% and 11 falling < 10%.
      CONCLUSIONS: These findings reflect the variability of lymphoblast
      cytomorphology, but also show a trend for cells to have more prominent nucleoli
      and greater size at relapse. Factors controlling these features of the FAB type
      are unknown, but they may simply be related to the growth fraction of a
      particular disease and not to any lineage specific biological feature.

PMID- 8543631
TI  - Screening criteria for beta thalassaemia trait in pregnant women.
AB  - AIMS: To establish suitable screening criteria for beta thalassaemia trait during
      pregnancy using an automated blood counter incorporating light scattering
      technology. METHODS: Pregnant women (n = 857) at a London antenatal clinic were
      investigated for beta thalassaemia trait if the Technicon H.2 full blood count
      showed either a mean corpuscular volume (MCV) < 85 fl or a mean corpuscular
      haemoglobin (MCH) < 27 pg. Results were then analysed to establish which of these
      variables was more suitable for screening and to determine suitable cut off
      points for calculating the haemoglobin A2 percentage. RESULTS: The MCH was
      superior to the MCV for thalassaemia screening as it was a more stable
      measurement and fewer unnecessary tests were performed. A MCH less than 27 pg is
      a suitable cut off point for screening. This screening criterion was equally
      applicable to a Coulter impedance counter. CONCLUSIONS: Pregnant women presenting
      at an antenatal clinic with a MCH < 27 pg should be investigated further to
      confirm or exclude a diagnosis of beta thalassaemia trait.

PMID- 8543632
TI  - Ceroid granulomas in the female genital system.
AB  - Three cases of ceroid granulomas of the female genital system are presented,
      involving the cervix in two and lesions in the ovaries and bowel serosa in the
      other. Ceroid granulomas are unusual and interesting lesions formed when suitable
      substrates accumulate within macrophages to such an extent that a relative lack
      of biological antioxidants results and auto-oxidation and conversion to ceroid is
      favoured. This may occur in the setting of haemorrhage and necrosis, whether from
      tumour necrosis or associated with endometriosis. Other sources of lipids and
      lipoproteins include bile, meconium and vernix caseosa.

PMID- 8543633
TI  - Pseudoangiosarcomatous carcinoma of the genitourinary tract.
AB  - Two cases of pseudoangiosarcomatous carcinoma of the genitourinary tract, arising
      in the vulva in one and the bladder in the other, are presented. In case 1, an 84
      year old woman, the vulvectomy specimen contained an irregular ulcerated tumour,
      infiltrating the left labia and extending into the clitoris. In case 2, a 59 year
      old woman, the excised bladder showed diffuse thickening of its wall by
      infiltrating haemorrhagic tumour. Both tumours showed focal keratinisation. This,
      in association with the presence of atypical squamous epithelium,
      immunohistochemistry and ultrastructural analysis, led to a diagnosis of
      pseudosarcomatous carcinoma in both cases. Pseudoangiosarcomatous carcinoma
      should be considered in the differential diagnosis of malignant angiomatoid
      tumours, particularly those that arise at sites, like the genitourinary tract,
      where angiosarcoma is rare.

PMID- 8543634
TI  - Elevated serum alpha-fetoprotein in a patient with undifferentiated carcinoma of
      the gall bladder.
AB  - An uncommon case of undifferentiated carcinoma of the gall bladder in a 65 year
      old Chinese man, who presented with an increased serum alpha-fetoprotein
      concentration, is reported. Histologically, the tumour had a primitive appearance
      and was composed of a pavement-like array of poorly differentiated
      columnar/polygonal cells. Alpha-fetoprotein was demonstrated in some of the
      tumour cells using an immunoperoxidase technique. Alpha-fetoprotein secretion in
      this instance may have occurred because the gall bladder and the liver are of
      similar embryological origin. Alpha-fetoprotein may also be related to the
      resurgent expression of oncofetal antigens. This tumour may represent another
      rare cause of increased serum alpha-fetoprotein concentrations.

PMID- 8543635
TI  - Lack of correlation of P-glycoprotein expression with response to MIC
      chemotherapy in oesophageal cancer.
AB  - The multidrug resistance gene product P-glycoprotein (P-GP) was assessed
      immunohistochemically (by antibody JSB-1) in biopsy specimens from 27 oesophageal
      squamous carcinomas and 10 adenocarcinomas before treatment with mitomycin,
      ifosfamide and cisplatin (MIC). Tumours were assessed following treatment and
      correlation with response sought. Of the squamous carcinomas, 74% (20/27)
      responded to MIC but only one expressed P-GP before and after treatment. Of the
      adenocarcinomas, 30% (three of 10) responded. Seven of the 10 adenocarcinomas
      expressed P-GP before treatment but all 10 were P-GP positive after chemotherapy.
      The difference in prevalence and induction of P-GP between the histological types
      was highly significant and may correlate with the greater response to MIC seen in
      squamous carcinomas compared with adenocarcinomas. P-GP cannot be used as a
      predictive marker of response as tumours express it inconsistently with response
      to MIC. Resistance to MIC may be due to other mechanisms.

PMID- 8543636
TI  - Do blood cultures need continuous monitoring so that clinical action can be taken
      outside normal working hours?
AB  - Many automated blood culture reading systems monitor bacterial growth 24 hours a
      day but it is unclear if reacting to prompts indicating bacterial growth outside
      normal laboratory hours is of clinical benefit. An analysis of 50 blood cultures
      from 43 patients which had organisms seen on Gram films and had triggered
      positive out-of-hours showed that examination of the Gram film altered management
      of seven patients and the results of culture or sensitivity testing altered that
      of a further four. However, after review, it was felt the clinical outcome would
      not have been influenced by earlier intervention in any of these patients. We
      therefore consider that an out-of-hours service for dealing with positive blood
      cultures is not justified in our hospital. This conclusion may not apply
      universally, especially in hospitals where potential pathogens show less
      predictable antimicrobial sensitivity patterns.

PMID- 8543637
TI  - Neomycin blood agar as a selective medium for vancomycin resistant Enterococcus
      faecium.
AB  - Neomycin blood agar is commonly used as a selective medium for the isolation of
      vancomycin resistant enterococci from faeces; however, not all isolates are
      recovered using this medium, perhaps because the neomycin concentrations are too
      high. To test this hypothesis, the neomycin minimum inhibitory concentration
      (MIC) was determined for 27 vancomycin resistant Enterococcus faecium isolates,
      14 from patients with leukaemia and 13 from patients on the renal unit. A further
      eight isolates that had been recovered from the faeces of patients on the renal
      unit on neomycin agar were also studied. Eleven of the 14 isolates from the
      patients with leukaemia showed equal recovery on neomycin agar and blood agar and
      had MICs > 64 mg/l. In three other isolates there was a 4log10 reduction in
      recovery on neomycin agar and the MIC was 8 mg/l. Two of the non-selected
      isolates from the renal unit were recovered equally on the two media, the other
      11 isolates showed a 4-5 log10 reduction in recovery. All eight faecal isolates
      recovered from patients on the renal unit on neomycin agar were highly resistant
      to neomycin (MIC > 64 mg/l). Comparative studies of screening media are urgently
      needed as vancomycin resistant enterococci become more prevalent nosocomial
      pathogens.

PMID- 8543638
TI  - Gold granuloma after accidental implantation.
AB  - A case, in a 66 year old man, of a florid granulomatous reaction to gold dental
      alloy presenting about 20 years after accidental implantation in the oral mucosa
      of the lip is reported. Subsequent energy dispersive analysis confirmed the
      presence of a high nobility gold dental alloy. Florid granulomatosis has only
      rarely been reported in association with gold. Possible explanations for the
      delay in presentation include alteration of immune status or the development of
      hypersensitivity with components of the gold dental alloy acting as haptens.

PMID- 8543639
TI  - Failure to detect Helicobacter pylori in nasal mucus in H pylori positive
      dyspeptic patients.
AB  - Stomach biopsies and samples of nasal mucus were cultured in patients with
      dyspeptic symptoms who underwent endoscopy to evaluate the possible route of
      transmission of Helicobacter pylori (H pylori). 42 patients were examined. For
      each patient two biopsies from the stomach corpus and antrum were taken and,
      before endoscopy, one nasal swab was obtained. Biopsy samples were tested for
      urease test, microbiological culture, and histological examination. The nasal
      swab was processed for microbiological examination. H pylori was not found in the
      nasal mucus of any of the patients, including the 36 who had H pylori in gastric
      biopsies.

PMID- 8543640
TI  - Job description of MLSOs.

PMID- 8543641
TI  - Prognostic factors in primary breast carcinoma.

PMID- 8543643
TI  - Diagnosis of Helicobacter pylori infection by specific gastric mucosal IgA and
      IgG pylori antibodies.
AB  - AIMS: To investigate the diagnostic value of mucosal IgA and IgG Helicobacter
      pylori antibodies. METHODS: The study population comprised 209 consecutive
      patients with severe dyspeptic complaints referred for upper gastrointestinal
      endoscopy. A positive culture or histological identification of H pylori in
      gastric biopsy specimens, or both, were used to confirm infection. Specific IgA
      and IgG H pylori antibodies were determined using a modified ELISA technique.
      RESULTS: Of the 209 patients, 137 were infected with H pylori. The diagnostic
      value of systemic IgA and IgG H pylori antibodies was confirmed. Systemic IgA
      antibodies had a sensitivity of 76.6% (95% confidence interval 69.5-83.7) and a
      specificity of 94.4% (89.1-99.7). The sensitivity and specificity for systemic
      IgG antibodies were, respectively, 97.1% (94.3-99.9) and 98.6% (95.9-100). A
      moderate but clinically important correlation was found between local and
      systemic IgA and IgG. Mucosal IgA H pylori antibodies had a sensitivity of 98.5%
      (96.5-100) and a specificity of 91.7% (85.3-98.1), while for IgG these figures
      were, respectively, 88.3% (82.9-93.7) and 98.6% (95.9-100). As a diagnostic test
      mucosal IgA H pylori antibodies were comparable with culture and histology.
      CONCLUSION: Determination of local IgA and IgG H pylori antibody levels is a
      highly sensitive and specific test for the diagnosis of H pylori infection.

PMID- 8543642
TI  - The age related amyloids: a growing family of unique biochemical substances.

PMID- 8543644
TI  - Early ultrastructural changes of antral mucosa with aspirin in the absence of
      Helicobacter pylori.
AB  - AIMS: To describe the ultrastructural changes that occur in human antral mucosa
      following direct application of aspirin in volunteers without Helicobacter pylori
      infection. METHODS: Ten healthy male volunteers without H pylori infection
      underwent three consecutive endoscopies (at zero, one and five hours). At the
      first endoscopy, two biopsy specimens were obtained (one for histology and the
      other for electron microscopy (EM)). At subsequent endoscopies, a single biopsy
      specimen was obtained for EM. A 50 ml solution of aspirin (concentration 3 mg/ml)
      was applied to the antral mucosa at the first endoscopy in five subjects; the
      other five subjects received 50 ml distilled water (placebo). RESULTS: The
      ultrastructural appearance of the first biopsy specimen in all subjects and
      subsequent biopsy specimens in the placebo treated subjects was normal. The
      aspirin treated group had evidence of intercellular oedema, widening of capillary
      fenestrae, rupturing of apical membranes, and dilatation of endoplasmic reticulum
      and mitochondria after one hour; these changes were more marked at five hours.
      Tight junctions were maintained. CONCLUSION: This is the first study to describe
      the early ultrastructural changes in antral mucosa induced by aspirin in subjects
      without H pylori infection.

PMID- 8543645
TI  - Perinatal and infant postmortem examinations: how well are we doing?
AB  - AIM: To investigate the quality of perinatal and infant necropsies and assess the
      relation between the quality and value of this investigation in different outcome
      groups. METHODS: Cohort analysis of 540 deaths during 1993 of babies between 20
      weeks' gestation and one year of age born to women usually resident in Wales.
      Cases were identified from the All Wales Perinatal Survey. Each case was assessed
      to establish whether the necropsy yielded clinically relevant information. The
      quality of necropsy was assessed by scoring aspects identified as being part of
      the necropsy. RESULTS: Necropsy was performed in 335 (62%) cases, and the report
      was available for assessment in 314 cases. The quality of necropsy was below the
      minimum standard in 46% (143/314) of cases. The highest quality necropsies were
      carried out on fetal deaths at 20 to 23 weeks' gestation (12% (10/85) below
      standard), compared with 65% (87/133) below standard on stillbirths and 68%
      (21/31) on sudden unexpected infant death. Overall, 42% (131/314) of necropsies
      were performed in a regional paediatric pathology centre including 88% (76/88) of
      fetal deaths, 23% (31/133) of stillbirths and 30% (29/96) of infant deaths. The
      quality score for the necropsy performed in a regional centre failed to achieve
      the minimum acceptable score in 8% (11/131) of cases compared with 72% (132/182)
      for those done elsewhere. The cause of death was detected by necropsy in 17%
      (52/314) of cases. The quality of necropsy was significantly higher when the
      cause of death was revealed than when nothing new was found. CONCLUSIONS: The
      overall quality of the perinatal and infant necropsy is poor. This is regrettable
      as valuable information can be revealed frequently by a good quality necropsy.
      Adherence to Guidelines for Postmortem Reports recently published by the Royal
      College of Pathologists should improve the situation.

PMID- 8543646
TI  - Patterns of thalamocortical degeneration after ablation of somatosensory cortex
      in monkeys.
AB  - We examined the pattern of cytochrome oxidase (CO), Nissl staining, and gamma
      amino butyric acid (GABA) immunoreactivity in the ventroposterior lateral nucleus
      (VPL) of the thalamus in monkeys that received no, total, or subtotal, ablation
      of the hand representations in postcentral somatosensory cortex. In unoperated
      animals, the region of VPL representing the hand was characterized by relatively
      dense and homogeneous CO staining throughout the rostral-caudal extent of VPL.
      Counts of neurons in the VPL hand representation from adjacent thalamic sections
      processed for Nissl and GABA immunostaining indicated that there were
      approximately 261.4 neurons/mm2 of which 78.4/mm2 stained positive for GABA.
      GABA(+) puncta-like terminals were readily apparent throughout the VPL. By
      contrast, animals that received total removals of the postcentral hand
      representations showed a dramatic reduction in CO staining in the VPL, which was
      confined to the expected location of the thalamic hand representation. Counts of
      neurons in the affected region from adjacent sections that underwent Nissl
      staining and GABA immunostaining also revealed a dramatic reduction of Nissl
      stained neurons, with a smaller reduction in the number of neurons staining
      positive for GABA. Specifically, large to medium-sized (> 180 microns 2) GABA(-)
      neurons were virtually eliminated in the affected portion of the VPL, and the
      numbers of GABA(+) neurons were significantly reduced. The remaining population
      of GABA(+) neurons was typically shrunken, and no GABA(+) puncta-like terminals
      were observed in the affected region. The results obtained after subtotal
      ablation of the postcentral hand representations (only one postcentral area
      spared, 3b or 3a) differed from those obtained when total removals were made.
      Instead of virtually complete degeneration of medium-sized to large neurons
      throughout the hand representation in VPL, as was the case with total removals,
      after partial removals, we found alternating regions in the VPL hand
      representation that appeared qualitatively normal, or dramatically degenerated.
      Thalamic sections stained with CO revealed light, moderate, and darkly stained
      patches of label within the hand representation in VP, depending on the type of
      cortical ablation. The most dramatic reduction of Nissl-stained neurons coincided
      precisely with the lightest staining CO patches. Interestingly, the only
      statistically significant reduction in the number of GABA(+) neurons occurred in
      the light CO patches. In the thalamic regions coincident with the dark and
      moderately stained CO patches, the number of medium-sized and large neurons
      decreased, but the number of GABA(+) neurons was comparable to normal. Optical
      density measurements of the dark patches also indicated a statistically
      significant difference from normal CO staining in this region.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8543647
TI  - Neurotransmitter receptors in the proliferative zones of the developing primate
      occipital lobe.
AB  - Film autoradiography was used to investigate the expression of several
      neurotransmitter receptor subtypes in the transient ventricular and
      subventricular proliferative zones of the developing occipital lobe in two groups
      of macaque monkey fetuses. The first group of fetuses were between 60 and 93 days
      after conception (E60-E93), when the ventricular and subventricular zones of the
      monkey occipital lobe produce neurons destined for the visual cortex. In the
      second group, fetuses were between E107 and E128, after generation of cortical
      neurons has ceased. In the E60-E93 group of fetuses, ventricular and
      subventricular zones displayed high densities of 5-HT1-serotonergic, D1
      dopaminergic, alpha 1- and alpha 2-adrenergic and high affinity kainate
      receptors. The activation of these receptors has previously been shown to
      stimulate cell proliferation in other cell systems. The possible involvement of
      these receptors in regulation of neuronal production is also supported by their
      absence in the deep laminae of the embryonic cerebral wall after E107, after
      cortical neurogenesis has been completed. The only exception is a high density of
      alpha 2-adrenergic receptors maintained near the ventricular surface long after
      all cortical neurons have been generated. We also found that during neurogenesis,
      proliferative zones in E66-E90 fetuses displayed virtually no 5-HT2-serotonergic,
      D2-dopaminergic, beta-adrenergic, M1-muscarinic cholinergic, gamma aminobutyric
      acid (GABA)A, N-methyl-D-aspartate (NMDA), or alpha-amino-3-hydroxy-5-menthy-4
      isoxazole proprionate (AMPA) sites; most of these receptor subtypes have been
      reported to mediate the suppression of cell proliferation. The present findings
      suggest that dividing and/or newly generated cortical neurons are capable of
      receiving specific signals from multiple neurotransmitters present in their
      environment.

PMID- 8543648
TI  - A population of wide-field bipolar cells in the rabbit's retina.
AB  - We have stained an unusual population of retinal bipolar cells. When the low
      molecular weight tracer biocytin was injected into the vitreous body of rabbits,
      it subsequently accumulated in the somata and processes of a population of wide
      field bipolar cells. The cells have 2-4 primary dendrites. Their dendritic arbors
      span a field 50 to 200 microns in diameter. The axonal arbors are sparse and
      often highly asymmetric. The longest dimension of the axonal arbor ranges from
      100 to 300 microns. The cells are moderately evenly spaced. They make up less
      than 1% of the total population of bipolar cells in the rabbit retina. With the
      whole population stained, regularities in the spatial arrangement of nearby cells
      can be recognized. Their dendrites often run to a common point, where they have
      the appearance of making contact with each other. A similar arrangement is seen
      for the cells' axonal arbors, so that the whole population is spatially linked in
      both the outer retina and the inner. The exact nature of the points of
      conjunction cannot be learned from light microscopy. One possibility is that the
      processes run together because they contact a common target. If so, the target
      structures (one in the outer retina and one in the inner) must be sparse. An
      alternative is that the points of conjunction represent synapses or gap junctions
      among wide-field bipolars of this type.

PMID- 8543649
TI  - Parallel pathways and convergence onto HVc and adjacent neostriatum of adult
      zebra finches (Taeniopygia guttata).
AB  - The structure and connectivity of the forebrain nucleus HVc, a site of
      sensorimotor integration in the song control system of oscine birds, were
      investigated in adult zebra finches. HVc in males comprises three
      cytoarchitectonic subdivisions: the commonly recognized central region with large
      and medium-sized darkly staining cells, a ventral caudomedial region with densely
      packed small and medium-sized cells, and a dorsolateral region with oblong cells
      and rows of cells. All three subdivisions project to area X and the robust
      nucleus of the archistriatum, with more complexity in the classes and
      distribution of cells than previously reported. In females, HVc is very small and
      has a cytoarchitecture distinct from that of the three male subdivisions. The
      structure of HVc in females treated with estradiol at 15 days of age is similar
      to male HVc. Tracer studies in males with fluorescent and biotinylated dextrans
      demonstrate non-topographic projections onto HVc that may carry auditory
      information, including type 1 and type 2 neurons in subdivisions L1 and L3 of the
      field L complex, a class of neurons in nucleus interface, nucleus uvaeformis, the
      caudal neostriatum ventral to HVc, and intrinsic HVc connections. These data are
      interpreted in terms of HVc's functional properties. Additionally, the
      neostriatum immediately ventral to HVc receives projections from field L, ventral
      hyperstriatum, and caudal neostriatum, and projects to a region surrounding RA
      and near to or into area X. The similarity of the connectivity of HVc and
      adjacent neostriatum suggests the possibility that they share a common origin.

PMID- 8543650
TI  - Asymmetrical blastomere origin and spatial domains of dopamine and neuropeptide Y
      amacrine subtypes in Xenopus tadpole retina.
AB  - Amacrine cells are located almost exclusively in the inner nuclear layer (INL) of
      the retina, but they express a variety of neurotransmitters. To begin to
      elucidate the relative roles of the local environment and cell lineage in
      determining the different neurotransmitter subtypes of amacrine cells, we
      combined lineage tracing and immunocytochemical techniques to map the spatial
      distribution and clonal origin of dopamine (DA) and neuropeptide Y (NPY) amacrine
      cells in Xenopus tadpole retina. At the earliest period of neurotransmitter
      expression, both DA and NPY amacrine cells were distributed preferentially in
      center and intermediate annular regions, and in anterior and dorsal quadrants.
      Most of the DA and NPY cells first emerged as scattered cells and later as
      clusters (of 2 or more cells) that increased in number and size up to
      premetamorphic stages. These results suggest that DA and NPY amacrine subtypes
      may be influenced by environmental cues localized to specific regions of the
      retina. Lineage analysis showed that the percentage of DA or NPY amacrine cells
      produced by most blastomere progenitors is significantly different from that
      predicted by the number of cells in the retina produced by those blastomeres.
      Only two blastomeres produced over 90% of the DA amacrine cells and only four
      produced 97% of the NPY amacrine cells. Some retinal progenitors did not
      contribute at all to these two amacrine subtypes. There also is a marked
      asymmetry in the blastomere origin of DA and NPY amacrine cells. Two retinal
      progenitors produced significant numbers of NPY but very few DA amacrine cells.
      This analysis provides evidence that blastomere origin restricts the
      developmental choices of retinal progenitors.

PMID- 8543651
TI  - NGF mRNA is expressed by GABAergic but not cholinergic neurons in rat basal
      forebrain.
AB  - Nerve growth factor (NGF) supports the survival and biosynthetic activities of
      basal forebrain cholinergic neurons and is expressed by neurons within lateral
      aspects of this system including the horizontal limb of the diagonal bands and
      magnocellular preoptic areas. In the present study, colormetric and isotopic in
      situ hybridization techniques were combined to identify the neurotransmitter
      phenotype of the NGF-producing cells in these two areas. Adult rat forebrain
      tissue was processed for the colocalization of mRNA for NGF with mRNA for either
      choline acetyltransferase, a cholinergic cell marker, or glutamic acid
      decarboxylase, a GABAergic cell marker. In both regions, many neurons were single
      labeled for choline acetyltransferase mRNA, but cells containing both choline
      acetyltransferase and NGF mRNA were not detected. In these fields, virtually all
      NGF mRNA-positive neurons contained glutamic acid decarboxylase mRNA. The double
      labeled cells comprised a subpopulation of GABAergic neurons; numerous cells
      labeled with glutamic acid decarboxylase cRNA alone were codistributed with the
      double-labeled neurons. These data demonstrate that in basal forebrain GABAergic
      neurons are the principal source of locally produced NGF.

PMID- 8543652
TI  - The development of interneurons in the chick embryo spinal cord following in vivo
      treatment with retinoic acid.
AB  - To investigate the role of retinoic acid (RA) in the development of interneurons
      in the spinal cord, we examined the expression of cellular retinoic acid binding
      protein type I (CRABP I). The earliest developing interneurons in the chick
      spinal cord can be divided into two major groups: circumferential (C) neurons and
      primitive longitudinal (PL) neurons. In brachial segments, both types of
      interneurons began to express CRABP I at stage (st.) 13+ of the V. Hamburger and
      H.L. Hamilton (1951, J. Morphol. 88:49-92) stage series, which is before the
      onset of axonogenesis. Subsequently, with the onset of axonal outgrowth, C
      neurons and PL neurons expressed CRABP I in their cell bodies, axons, and growth
      cones. The expression of CRABP I was developmentally regulated. CRABP I
      immunoreactivity gradually decreased after st. 36 (embryonic day [E] 10) such
      that no interneurons expressed this protein by E21. The transient expression of
      CRABP I during a period of intensive axonal growth suggested that RA may be
      involved in the development of interneurons. To test this idea, we implanted an
      all-trans RA-containing ion exchange bead into either rostral segments of the
      spinal cord at st. 12-13 or into caudal segments at st. 15-16, all stages that
      are well before the appearance of CRABP-I-positive neurons in these segments. In
      the RA-treated spinal cord, increased numbers of pyknotic cells were found
      predominantly in dorsal regions, presumably reflecting the death of
      neuroepithelial cells, C neurons and premigratory neural crest cells. Surviving C
      neurons in the RA-treated spinal cord extended their axons ventrally toward the
      floor plate as in control embryos. PL neurons also projected their axons
      rostrally or caudally in the RA-treated spinal cord, similarly to control
      embryos. However, the proportion of caudally projecting PL neurons was
      significantly increased in segments rostral to the RA-containing bead. These
      results suggest that RA may regulate the survival and axonal orientation
      (directionality) of subpopulations of spinal interneurons.

PMID- 8543653
TI  - Calretinin immunoreactive structures in the human hippocampal formation.
AB  - The calcium-binding protein calretinin is present in an intrinsic GABAergic and
      an extrinsic non-GABAergic system in the rat and monkey hippocampal formation.
      Important species differences have been noted in hippocampal cell types
      immunostained for calretinin and the termination pattern of calretinin containing
      hypothalamic afferents in the hippocampus. In the present study, calretinin
      containing neurons were visualized using immunocytochemistry in the human
      hippocampal formation of individuals which showed no significant
      neuropathological alterations. Calretinin-immunoreactivity was present
      exclusively in non-granule cells of the dentate gyrus and in non-pyramidal cells
      of Ammon's horn. Calretinin-positive neurons were found most frequently in the
      hilus of the fascia dentata and in strata radiatum and lacunosum-moleculare of
      CA1, whereas neurons in CA2 and CA3 were rarely immunostained. The majority of
      calretinin-immunoreactive neurons were small, bipolar or fusiform neurons. The
      dendritic trees of the calretinin-positive neurons were, for the most part,
      parallel to the dendrites of the principal cells. In the hilus, however, we
      observed cells with dendrites restricted to the hilar area. These dendrites were
      parallel to the granule cell layer. In the stratum lacunosum-moleculare, neurons
      with dendrites oriented parallel to the hippocampal fissure were frequently
      detected. In general, dendrites were smooth or sparsely spiny, displaying small
      conventional spines. The axons usually emerged from the proximal dendrite and
      could be followed over long distances. Axons were thin, had small varicosities
      and displayed only few collaterals which branched relatively far away from the
      cell body. Distinct bands of darkly stained calretinin-positive fibers occupied
      the innermost portion of the dentate molecular layer and the pyramidal cell layer
      of CA2. This distribution of calretinin-immunoreactive structures in the human
      hippocampus is similar to that observed in other primates but differs from that
      described in lower mammals, i.e., the rat. Our findings suggest that primates may
      share a common hippocampal calretinin-containing system, presumably both the
      intrinsic GABAergic and the extrinsic hypothalamic non-GABAergic components.

PMID- 8543654
TI  - Ontogeny of the striatal neurons expressing neuropeptide genes in the human fetus
      and neonate.
AB  - The distribution patterns of neurons expressing mRNAs for four neuropeptides in
      the human striatum were studied during ontogeny by the use of in situ
      hybridization. The results of our study demonstrate that somatostatin,
      enkephalin, dynorphin, and substance P mRNAs are present in striatal neuronal
      populations from week 12 of fetal life. Each neuronal population undergoes a
      specific differentiation. Neurons containing somatostatin mRNA are scattered
      throughout the caudate-putamen up until birth. Neurons containing enkephalin,
      dynorphin, or substance P mRNAs evolve throughout fetal life in relation to
      caudate-putamen and patch-matrix compartmentalization. Neurons containing
      enkephalin mRNA (distinct from those containing substance P or dynorphin mRNAs)
      are present in the matrix from week 12 of fetal life. These neurons are
      preferentially distributed in the matrix and, at birth, display higher enkephalin
      mRNA content in the matrix than in the patches. Dynorphin mRNA is found in the
      caudate and putamen, preferentially in the patch neurons; nevertheless, a low
      level of dynorphin mRNA is also present in neurons of the caudate matrix.
      Substance P mRNA is initially restricted to caudate neurons. At birth, both
      substance P and dynorphin mRNAs are expressed at high levels in the patches.
      These results demonstrate that each neuropeptide gene is expressed during human
      fetal life in neurons with a specific topology and pace of development in
      relation to caudate-putamen and patch-matrix differentiation. These results also
      contribute evidence that neurochemical evolution of the striatal neuronal
      populations is not complete at birth in humans.

PMID- 8543655
TI  - Acute exposure to alcohol during early postnatal life causes a deficit in the
      total number of cerebellar Purkinje cells in the rat.
AB  - Alcohol taken regularly over a lengthy period of time has been claimed to cause
      the loss of neurons in both the adult and developing brain. However, it remains
      uncertain whether acute, as opposed to chronic, exposure to alcohol at specified
      periods can also cause disruption in the neuronal population of the developing
      brain. This question was investigated by exposing Wistar rat pups to 7.5 g/kg
      body weight of ethanol administered as a 10% solution via an intragastric cannula
      over an 8 hour period either on the 5th (PND5) or the 10th (PND10) postnatal day
      of age. Gastrostomy controls received a 5% sucrose solution substituted
      isocalorically for the ethanol. Another set of pups raised by their mothers was
      used as "suckle controls." All surgical procedures were carried out under
      halothane vapour anaesthesia. After the artificial feeding regimes, all pups were
      returned to the lactating dams and weaned at 21 days of age. Between 52 and 54
      days of age, the rats were anaesthetised with an intraperitoneal injection with
      Nembutal and killed by intracardiac perfusion with 3% glutaraldehyde in 0.1 M
      phosphate buffer. The relatively unbiased stereological procedure known as the
      "fractionator" method was used to estimate the total number of Purkinje cells in
      the cerebellum of each animal. The Purkinje cell nucleolus was used as the
      counting unit; it was assumed that each Purkinje cell contained only one
      nucleolus. PND10 ethanol-treated rats and gastrostomy and suckle controls had
      between about 210,000-232,000 Purkinje cells in the cerebellum. However, the PND5
      ethanol-treated rats had only about 137,000 Purkinje cells.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8543656
TI  - Chemoarchitectonics and corticocortical terminations within the superior temporal
      sulcus of the rhesus monkey: evidence for subdivisions of superior temporal
      polysensory cortex.
AB  - Cortex of the upper bank of the superior temporal sulcus (STS) in macaque
      monkeys, termed the superior temporal polysensory (STP) region, corresponds
      largely to architectonic area TPO and is connectionally distinct from adjacent
      visual areas. To investigate whether or not the STP region contains separate
      subdivisions, immunostaining for parvalbumin and neurofilament protein (using the
      SMI-32 antibody) was compared with patterns of corticocortical terminations in
      the STS. Chemoarchitectonic results provided evidence for three caudal-to-rostral
      subdivisions: TPOc, TPOi, and TPOr. Area TPOc was characterized by patchy
      staining for parvalbumin and SMI-32 in cortical layers IV/III and III,
      respectively. Area TPOi had more uniform chemoarchitectonic staining, whereas
      area TPOr had a thicker layer IV than TPOi. The connectional results showed
      prefrontal cortex in the location of the frontal eye fields (area 8) and dorsal
      area 46 projected in a columnar pattern to all cortical layers of area TPOc, to
      layer IV of TPOi, and in a columnar fashion, with a moderate increase in density
      in layer IV, to TPOr. In TPOc, columns of frontal connections showed a
      periodicity similar to that of the SMI-32 staining. The caudal inferior parietal
      lobule (area 7a) and superior temporal gyrus projected to each subdivision of
      area TPO, displaying either panlaminar or fourth-layer terminations. In addition
      to STP cortex, parvalbumin and SMI-32 immunostaining allowed identification of
      caudal visual areas of the STS, including MT, MST, FST, and V4t. These areas
      received first- and sixth-layer projections from prefrontal cortex and area 7a.

PMID- 8543657
TI  - Variability and partial synchrony of the cell cycle in the germinal zone of the
      early embryonic cerebral cortex.
AB  - Cell cycle parameters were estimated using the cumulative 3H-thymidine S-phase
      labeling and percentage of labeled mitoses methods in the embryonic day 14 and 15
      germinal zone of the rat cerebral cortex. The shortest cell cycle time was seen
      in the dorsal neocortex and the longest in the lateral neocortex and fimbria (the
      latter also had a low growth fraction). No differences were observed in cell
      cycle times between the cells in the ventricular and subventricular zone in the
      same neocortical region. The results suggest gradients of lengthening cell cycle
      times extending ventrolaterally and ventromedially from the dorsomedial
      neocortex. Although a majority of proliferating cells in individual cortical
      regions seem to belong to one population in terms of cell kinetics, several
      pieces of evidence suggest some heterogeneity: the asymmetric shapes of the
      percentages of labeled mitoses curves, the small population of noncycling
      neuroepithelial cells in the neocortex and mesocortex, and small population of
      cells that become pyknotic. Groups of DNA-synthesizing nuclei that were
      ectopically located in the inner half of the ventricular zone also indicate the
      existence of different subpopulations of neuroepithelial cells. In addition,
      after a pulse injection of 3H-thymidine the germinal zone is characterized by
      alternating clusters of heavily and lightly labeled cell nuclei that may reflect
      the simultaneous passage of a cluster of cells through the same portion of S
      phase. We suggest that partial cell cycle synchrony within groups of ventricular
      cells may explain the presence of these iterative cell kinetic patterns in the
      developing cortex.

PMID- 8543658
TI  - Molecular basis of interactions between regenerating adult rat thalamic axons and
      Schwann cells in peripheral nerve grafts I. Neural cell adhesion molecules.
AB  - To gain insight into the possible molecular mechanisms underlying axonal
      regeneration of neurons of the adult central nervous system (CNS), we have
      investigated, by in situ hybridization and by immunocytochemistry, the
      localization and sites of synthesis of the neurite outgrowth-promoting cell
      surface molecules L1, N-CAM and its highly sialylated form, N-CAM-PSA, in and
      around peripheral nerve grafts implanted into the thalamus of adult rats. Normal
      unoperated adult rat thalamus contains N-CAM and L1 but no N-CAM-PSA
      immunoreactive axons. Between 7 days and 13 weeks after graft implantation, L1, N
      CAM and N-CAM-PSA were all present at the surface of axonal sprouts in the brain
      parenchyma close to grafts and in the central parts of Schwann cell columns
      within grafts. Schwann cell membranes were L1 and N-CAM positive at all postgraft
      survival times, more strongly at 2-4 weeks than other times, but were associated
      with N-CAM-PSA reaction product only where they abutted N-CAM-PSA positive axons.
      Schwann cell membranes apposed to basal laminae (which were avoided by
      regenerating CNS axons) were L1, N-CAM and N-CAM-PSA negative. Between 3 days and
      8 weeks after grafting, N-CAM and L1 mRNA were generally weakly upregulated in
      neurons of the ipsilateral thalamus, but, most conspicuously, L1 mRNA was
      strongly upregulated in the neurons of the thalamic reticular nucleus; these
      neurons are known to regenerate axons very effectively into peripheral nerve
      grafts and are the probable source of most of the axons which enter thalamic
      grafts. N-CAM and L1 mRNA were also strongly upregulated in presumptive Schwann
      cells in the graft. These results show that regenerating CNS axons (re)express N
      CAM-PSA and upregulate L1 and N-CAM, suggesting that all of these molecules may
      play a role in cellular interactions during the regeneration of CNS axons.
      Furthermore L1 synthesis appears to be particularly well correlated with the
      ability of CNS neurons to regenerate axons into peripheral nerve grafts.

PMID- 8543659
TI  - Molecular basis of interactions between regenerating adult rat thalamic axons and
      Schwann cells in peripheral nerve grafts. II. Tenascin-C.
AB  - Tenascin-C is a developmentally regulated extracellular matrix component. There
      is evidence that it may be involved in axon growth and regeneration in peripheral
      nerves. We have used in situ hybridization and immunocytochemistry to investigate
      the association of tenascin-C with central nervous system axons regenerating
      through a peripheral nerve autograft inserted into the thalamus of adult rats.
      Between 3 days and 4 weeks after implantation, tenascin-C immunoreactivity was
      increased in the grafts, first at the graft/brain interface, then in the
      endoneurium of the graft, and finally within the Schwann cell columns of the
      graft. By electron microscopy, reaction product was present around collagen
      fibrils and basal laminae in the endoneurium, but the heaviest deposits were
      found at the surface of regenerating thalamic axons within Schwann cell columns.
      Schwann cell surfaces were not associated with tenascin-C reaction product except
      where they faced the tenascin-rich basal lamina or were immediately opposite
      axons surrounded by tenascin-C. By 8 weeks after graft implantation tenascin-C in
      the endoneurium and around axons of the graft was decreased. In the brain
      parenchyma around the proximal part of the graft, axonal sprouts associated with
      tenascin-C could not be identified earlier than 2 weeks after grafting and were
      sparse at this stage. Larger numbers of such axons were present at 8-13 weeks
      after grafting and were located predominantly where the glia limitans between
      brain and graft appeared to be incomplete, suggesting that the tenascin-C may
      have penetrated the brain parenchyma from the graft. By in situ hybridization,
      cells expressing tenascin-C mRNA (probably Schwann cells) appeared first at the
      brain/graft interface 3 days after grafting and thereafter were mainly located
      within the grafts. Lightly labelled cells containing tenascin-C mRNA (probably
      glial cells) were scattered in the thalamic parenchyma both ipsilateral and
      contralateral to the graft and a few heavily labelled cells were located very
      close to the tip of the graft. These results show that regenerating adult
      thalamic axons, unlike regenerating peripheral axons, become intimately
      associated with peripheral nerve graft-derived tenascin-C, suggesting that they
      express a tenascin-C receptor, as many neurons do during development, and that
      tenascin-C derived from Schwann cells may play a role in the regenerative growth
      of such axons through the grafts.

PMID- 8543660
TI  - Distribution of brainstem projections from spinal lamina I neurons in the cat and
      the monkey.
AB  - The distribution of terminal projections in the brainstem from lamina I neurons
      in the spinal dorsal horn was investigated with the anterograde tracer Phaseolus
      vulgaris-leucoagglutinin in the cat and the cynomolgus monkey. Iontophoretic
      injections made with physiological guidance were restricted to lamina I or to
      laminae I-III in the cervical (C6-8) or lumbar (L6-7) enlargement. The
      distribution of terminal labeling was essentially identical in the cat and the
      monkey, although consistently of greater intensity in the monkey. Terminations
      were observed in the solitary nucleus, the dorsomedial medullary reticular
      formation, the entire rostrocaudal extent of the ventrolateral medulla, the locus
      coeruleus, the subcoerulear region and the Kolliker-Fuse nucleus, the lateral and
      medial portions of the parabrachial nucleus, the cuneiform nucleus, the
      ventrolateral and lateral portions of the periaqueductal gray, and the
      intercollicular nucleus. Lamina I terminations were generally bilateral in the
      medulla but more dense contralaterally in the pons and mesencephalon. The density
      and laterality of labeling in the medulla varied between cases independently from
      that in the pons and mesencephalon, suggesting that the lamina I projections to
      these regions may originate from different subsets of neurons. A clear
      topographic organization was observed only in the lateral column of the
      periaqueductal gray, where lumbar lamina I terminations were found caudal to
      cervical terminations. These observations indicate that spinal lamina I neurons
      project to a variety of brainstem sites involved in autonomic (cardiovascular,
      respiratory) and homeostatic processing and the control of behavioral state.
      These projections provide an afferent substrate for spino-bulbo-spinal
      somatoautonomic reflex arcs activated by nociceptive, thermoreceptive activity
      and for a spino-bulbo-hypothalamic relay of such activity by cells in the caudal
      ventrolateral medulla. These observations support the general concept that lamina
      I projections distribute modality-selective sensory information relevant to the
      physiological status and maintenance of the tissues and organs of the entire
      organism.

PMID- 8543661
TI  - Cell and molecular analysis of the developing and adult mouse subventricular zone
      of the cerebral hemispheres.
AB  - The subventricular zone (SVZ) of the lateral ventricle remains mitotically active
      in the adult mammalian central nervous system (CNS). Recent studies have
      suggested that this region may contain neuronal precursors (neural stem cells) in
      adult rodents. A variety of neuronal and glial markers as well as three
      extracellular matrix (ECM) markers were examined with the hope of understanding
      factors that may affect the growth and migration of neurons from this region
      throughout development and in the adult. This study has characterized the
      subventricular zone of late embryonic, postnatal, and adult mice using several
      neuronal markers [TuJ1, nicotinamide adenine dinucleotide phosphate diaphorase
      (NADPH-d), neuron-specific enolase (NSE)], glial markers [RC-2, vimentin, glial
      fibrillary acidic protein (GFAP), galactocerebroside (Gal-C)], ECM markers
      [tenascin-C (TN-C), chondroitin sulfate, a chondroitin sulfate proteoglycan
      termed dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG)], stem-cell marker
      (nestin), and proliferation-specific marker [bromodeoxyuridine (BrdU)]. TuJ1+ and
      nestin+ cells (neurons and stem cells, respectively) persist in the region into
      adulthood, although the numbers of these cells become more sparse as the animal
      develops, and they appear to be immature compared to the cells in surrounding
      forebrain structures (e.g., not expressing NSE and having few, if any,
      processes). Likewise, NADPH-d+ cells are found in and around the SVZ during early
      postnatal development but become more sparse in the proliferative zone through
      maturity, and, by adulthood, only a few labeled cells can be found at the border
      between the SVZ and surrounding forebrain structures (e.g., the striatum), and
      even smaller numbers of positive cells can be found within the adult SVZ proper.
      BrdU labeling also seems to decrease significantly after the first postnatal
      week, but it still persists in the SVZ of adult animals. The disappearance of RC
      2+ (radial) glia during postnatal development and the persistence of glial
      derived ECM molecules such as tenascin and chondroitin sulfate proteoglycans (as
      well as other "boundary" molecules) in the adult SVZ may be associated with a
      persistence of immaturity, cell death, and a lack of cell emigration from the SVZ
      in the adult.

PMID- 8543662
TI  - Oculomotor control in calliphorid flies: organization of descending neurons to
      neck motor neurons responding to visual stimuli.
AB  - In insects, head movements are mediated by neck muscles supplied by nerves
      originating in the brain and prothoracic ganglion. Extracellular recordings of
      the nerves demonstrate units that respond to visual stimulation of the compound
      eyes and to mechanosensory stimulation of the halteres. The number of neck
      muscles required for optokinetic eye movements in flies is not known, although in
      other taxa, eye movements can involve as few as three pairs of muscles. This
      study investigates which neck motor neurons are likely to be involved in head
      movements by examining the relationships between neck muscle motor neurons and
      the terminals visiting them from approximately 50 pairs of descending neurons.
      Many of these descending neurons have dendrites in neuropils that are associated
      with modalities other than vision, and recording show that visual stimuli
      activate only a few neck motor neurons, such as the sclerite depressor neurons,
      which respond to local or wide-field, directionally specific motion, as do a
      subset of descending neurons coupled to them. The results suggest that, like in
      the vertebrate eye or the retinas of jumping spiders, optokinetic head movements
      of flies require only a few muscles. In addition to the importance of visual
      inputs, a major supply to neck muscle centers by nonvisual descending neurons
      suggests a role for tactile, gustatory, and olfactory signals in controlling head
      position.

PMID- 8543663
TI  - Oculomotor control in calliphorid flies: head movements during activation and
      inhibition of neck motor neurons corroborate neuroanatomical predictions.
AB  - In tethered flying flies, moving contrast gratings or small spots elicit head
      movements which are suited to track retinal images moving at velocities up to
      3,000 degrees/sec (about 50 Hz contrast frequency for gratings of spatial
      wavelength 15 degrees). To investigate the neural basis of these movements we
      have combined videomicroscopy with electrophysiological stimulation and recording
      to demonstrate that excitation of prothoracic motor neurons projecting in the
      anterodorsal (ADN) and frontal nerves (FN), respectively, generates the yaw and
      roll head movements measured behaviorally. Electrical stimulation of the ADN
      produces head yaw. The visual stimuli which excite the two ADN motor neurons (ADN
      MNs) are horizontal motion of gratings or spots moving clockwise around the yaw
      axis in the case of the right ADN (counterclockwise for left ADN). Activity is
      inhibited by motion in the opposite direction. Spatial sensitivity varies in the
      yaw plane with a maximum between 0 degree and 40 degrees ipsilaterally, but both
      excitation and inhibition are elicited out to 80 degrees in the ipsilateral and
      contralateral fields. ADN MNs respond to contrast frequencies up to 15-20 Hz,
      with a peak around 2-4 Hz for grating motion in the excitatory or inhibitory
      directions. Electrical stimulation of the FN primarily elicits roll down to the
      ipsilateral side. The one FN MN consistently driven by visual stimulation is
      excited by downward motion and inhibited by upward motion at 80 degrees azimuth
      in the ipsilateral visual field. At -80 degrees contralateral, visual motion has
      the opposite effect: Upward is excitatory and downward is inhibitory. The FN MN
      is tuned to contrast frequencies in the same range as the ADN MNs, with peak
      sensitivity around 4 Hz. The functional organization of inputs to the ADN and FN
      is discussed with respect to identified visual interneurons and parallel pathways
      controlling motor output.

PMID- 8543664
TI  - Oculomotor control in calliphorid flies: GABAergic organization in heterolateral
      inhibitory pathways.
AB  - In calliphorid Diptera, motor neurons mediating visually evoked head movements
      can be excited or inhibited by visual stimuli, depending on the directionality of
      the stimulus and whether it is in the ipsi- or contralateral visual field. The
      level at which inhibition occurs is of special interest because binocular
      activation of homolateral tangential neurons in the lobula plate demonstrates
      that excitatory interaction must occur between the left and right optic lobes.
      Recordings and dye fillings demonstrate a variety of motion-sensitive
      heterolateral pathways between the lobula plates, or between them and
      contralateral deutocerebral neuropil, which provides descending pathways to neck
      motor centers. The profiles of heterolateral tangential cells correspond to
      neurons stained by an antibody against gamma-aminobutyric acid (GABA). Other GABA
      immunoreactive interneurons linking each side of the brain correspond to uniquely
      identified motion-sensitive neurons linking the deutocerebral. Additional
      inhibitory pathways include heterolateral GABAergic descending and ascending
      neurons, as well as heterolateral GABAergic neurons in the thoracic ganglia. The
      functional significance of heterolateral GABAergic pathways was tested surgically
      by making selective microlesions and monitoring the oculomotor output. The
      results demonstrate an important new attribute of the insect visual system.
      Although lesions can initially abolish an excitatory or inhibitory response, this
      response is reestablished through alternative pathways that provide inhibitory
      and excitatory information to the same motor neurons.

PMID- 8543666
TI  - Spinovestibular projections in the rat, with particular reference to projections
      from the central cervical nucleus to the lateral vestibular nucleus.
AB  - Projections from the spinal cord to the vestibular nuclei were examined following
      injections of Phaseolus vulgaris-leucoagglutinin, cholera toxin subunit B, or
      biotinylated dextran at various levels of the spinal cord in the rat. Labeled
      terminals were abundant after injections of the tracers into the C2 and C3
      segments containing the central cervical nucleus. Labeled terminals were seen in
      the descending vestibular nucleus and the parvocellular, magnocellular, and
      caudal parts of the medial vestibular nucleus throughout its rostrocaudal extent.
      Labeled terminals were most numerous in the lateral vestibular nucleus throughout
      its rostrocaudal extent. The projections from the central cervical nucleus to the
      vestibular nuclei were exclusively contralateral to the cells of origin because
      the axons of the central cervical nucleus neurons cross in the spinal cord.
      Following tracer injections in the cervical enlargement, many labeled terminals
      were seen in the magnocellular part of the medial vestibular nucleus, but a few
      were seen in the lateral and the descending vestibular nucleus. Injections into
      more caudal segments resulted in sporadic terminal labeling in the magnocellular
      part of the medial vestibular nucleus, the descending vestibular nucleus, and the
      caudal part of the lateral vestibular nucleus. The results indicate that primary
      neck afferent input relayed at the central cervical nucleus is mediated directly
      to the contralateral vestibular nuclei. It is suggested that this projection
      serves as an important linkage from the upper cervical segments to the lateral
      vestibulospinal tract in the tonic neck reflex.

PMID- 8543665
TI  - The guidance molecule semaphorin III is expressed in regions of spinal cord and
      periphery avoided by growing sensory axons.
AB  - The protein collapsin was purified from chick brain on the basis of its ability
      to inhibit sensory neuron growth cones, implicating this molecule in sensory axon
      guidance (Luo et al. [1993] Cell 75:217-227). To examine the relationship between
      collapsin and sensory axon growth, we examined the pattern of mRNA expression of
      collapsin's mammalian paralogue, Semaphorin III (Sema III), and compared it to
      dorsal root ganglion (DRG) axon pathways in the developing rat embryo. Centrally,
      DRG axons enter the spinal cord by embryonic (E) 11 and branch into the gray
      matter by E15 in brachial and thoracic regions. Laminar specific targets are
      reached by E17. Between E13 and E17, Sema III mRNA is expressed at high levels in
      the entire ventral half of the spinal cord except the floor plate. This pattern
      suggests that Sema III may inhibit non-proprioceptive sensory axons from
      penetrating the ventral spinal cord. Peripherally, sensory axons have entered the
      anterior sclerotome by E11 at all rostrocaudal levels. At this age, Sema III mRNA
      is already expressed in the dermamyotome and ventral aspect of the posterior
      sclerotome, areas which axons pass between but do not penetrate en route to their
      peripheral targets. From E12 to E15, the axons lengthen and branch into smaller
      fascicles which extend toward peripheral targets. During this time, Sema III mRNA
      is expressed by many mesodermal structures surrounding the axon fascicles, with
      highest levels observed in the dermamyotome, perinotochordal mesenchyme, pelvic
      girdle, and limb. As development proceeds, Sema III mRNA expression is quickly
      downregulated before disappearing by birth. Taken together, our results
      demonstrate that the gene for Sema III is expressed in central and peripheral
      regions which are avoided by growing DRG axons. These findings are consistent
      with the idea that Sema III inhibits growth and branching of axons into
      inappropriate areas during development.

PMID- 8543667
TI  - Intrinsic connections of the rat amygdaloid complex: projections originating in
      the basal nucleus.
AB  - The amygdaloid complex is involved in associational processes, such as the
      formation of emotional memories about sensory stimuli. However, the anatomical
      connections through which the different amygdaloid nuclei process incoming
      information and communicate with the other amygdaloid nuclei, is poorly
      understood. As part of an ongoing project aimed at elucidating the intrinsic
      connections of the rat amygdaloid complex, we injected the anterograde tracer PHA
      L (Phaseolus vulgaris-leucoagglutinin) into different rostrocaudal levels of the
      basal nucleus of the amygdala in 21 rats and analyzed the distribution of labeled
      fibers and terminals throughout the amygdaloid complex. The connectional
      analysis, together with cytoarchitectonic observations, suggested that contrary
      to previous notions the basal nucleus in the rat has three divisions:
      magnocellular, intermediate, and parvicellular. The magnocellular division has
      heavy reciprocal connections with the lateral portion of the parvicellular
      division and the intermediate division projects weakly to the parvicellular
      division, whereas the projection from the medial portion of the parvicellular
      division to the intermediate division is heavy and the lateral and medial
      portions of the parvicellular division are only weakly interconnected, as are the
      magnocellular and intermediate divisions. The main intraamygdaloid targets of the
      basal nucleus projections are the nucleus of the lateral olfactory tract, the
      anterior amygdaloid area, the medial and capsular divisions of the central
      nucleus, the anterior cortical nucleus, and the amygdalohippocampal area. Our
      findings provide the most detailed understanding of the intra-amygdala
      connections of the basal nucleus to date and show that the connections within the
      basal nucleus and between the basal nucleus and other amygdaloid areas are more
      widespread and topographically organized than previously recognized.

PMID- 8543668
TI  - Ultrastructural studies of the epiphyseal plate of chicks fed a vitamin D
      deficient and low-calcium diet.
AB  - The epiphyseal plates of rachitic chicks fed a vitamin D-deficient and low
      calcium diet were examined ultrastructurally at 4, 7, 14, 18 and 21 days old. On
      and after 14 days, changes were observed. Chondrocytes in resting, proliferating
      and maturing zones commonly showed a reduction in cell organelles, suggestive of
      a decrease in synthetic activity of matrix components. In addition, the resting
      zone cells had numerous intracytoplasmic microfilaments. Mitotic figures were
      present but not increased in number in the proliferating zone. Autolysosome-like
      dense bodies in the chondrocytes and clusters of degenerative and necrotic
      chondrocytes were observed in the proliferating and maturing zones. In the
      calcifying zone of the rachitic epiphyseal plate, initial calcification was
      observed characterized by the deposition of apatite crystals in matrix vesicles
      and the formation of spherical crystal clusters. The crystal clusters were
      separated from each other by collagen fibrils on which only small amounts of
      apatite crystals had been deposited. In this zone, hypertrophic chondrocytes
      responsible for the initial calcification were seen, but not the stellate
      chondrocytes responsible for the progression of matrix calcification after its
      initiation. These findings suggest that accumulation of the proliferating and
      maturing zone cells as a characteristic lesion of the epiphyseal plate in
      rachitic chicks is caused by a disturbance of cell maturation. Such disturbance
      in the calcifying zone may explain the progression of the defect in matrix
      calcification.

PMID- 8543669
TI  - Pathology of canine bladder and urethral cancer and correlation with tumour
      progression and survival.
AB  - Biopsy and necropsy specimens, comprising 107 primary carcinomas and three
      mesenchymal tumours, were reviewed from 110 dogs with cancer of the bladder,
      urethra, or both. Histological classifications developed for the assessment of
      human bladder cancer were found to be readily applicable to the dog. These
      classifications are based on histological features, including the pattern of
      growth, the cell type, the grade of transitional tumour and the depth of invasion
      of the bladder wall. Features associated with localized disease in canine
      transitional cell carcinoma included papillary architecture, "in-situ" tumour,
      low tumour grade and a strong peritumoral lymphoid cell reaction. Features of
      tumours with metastasis included infiltrating and non-papillary architecture,
      increasing tumour grade, depth of invasion, vascular invasion and presence of
      peritumoral fibrosing reaction. Wide variability was found within single tissue
      samples, indicating that multiple sample sites are necessary for the adequate
      characterization of a given lesion. Statistically significant correlations were
      found between: tumour grade and depth of invasion (P < 0.0001); tumour grade and
      presence of metastases (P < 0.029); and peritumoral desmoplasia and metastases (P
      < 0.029). It was concluded that canine bladder cancer could be classified for the
      purpose of clinical management with a modified World Health Organization system
      as developed for human tumours.

PMID- 8543670
TI  - Inherited muscular disorder in mutant Japanese quail (Coturnix coturnix
      japonica): relationship between the development of muscle lesions and age.
AB  - The progression of the pathological changes that occur in the skeletal muscle was
      examined in 19 Japanese quail of the LWC strain, affected with an autosomal
      dominant inherited muscular disorder producing electrical myotonia. The muscle
      samples were obtained every 10 days from 20 to 70 days of age. Muscle samples
      from 18 age-matched commercial quail were used as normal controls. Characteristic
      histological lesions found in the skeletal muscles included sarcoplasmic masses,
      ringed fibres, internal migration of nuclei and fibre size variation. These
      lesions, which mainly occurred in the proximal muscles, appeared first in the
      pectoral region and later in the muscles of the thoracic and pelvic limbs. The
      most predominant lesion observed at all ages consisted of sarcoplasmic masses.
      The presence of histological changes did not affect muscle fibre typing by two
      staining methods, for myosin ATPase at pH 4.5, and by NADH-TR stain. The
      histological changes were observed in type 2A and less commonly in 2B fibres, but
      not in type 1. The pectoralis thoracicus muscle, in which lesions were
      particularly common, showed abnormally large type 2B muscle fibres at 20 days of
      age. These fibres began to decrease in size at 30 days of age, and at 70 days had
      become strikingly atrophic, their diameter being only about half that observed at
      20 days. The atrophic type 2B muscle fibres were eventually replaced by
      lipocytes. Chronological staging of the histopathological changes in muscle was
      impossible since no inter-relationship was observed between the age of the quail,
      the severity of clinical signs and the extent of muscle lesions. This variability
      in the severity and age of onset may have been due to the variable expression or
      incomplete penetrance of the defective gene. Because the disorder is hereditary
      and progressive in nature, it can be classified as a type of progressive muscular
      dystrophy.

PMID- 8543671
TI  - Trichostrongylus colubriformis infection in rabbits: persistence of the distal
      adaptive response to parasitism after anthelmintic treatment.
AB  - Mucosal changes associated with anthelmintic treatment in Trichostrongylus
      colubriformis-infected rabbits were assessed along the entire length of the small
      intestine. The following groups, each of five rabbits, were compared: infected
      (group I); infected and treated on day 21 with fenbendazole (group IT);
      uninfected but given fenbendazole on day 21 (group C, controls). All animals were
      killed on day 28. In the proximal part of the small intestine of group I rabbits,
      the worms were associated with shortening of the villi and a significant
      depletion in alkaline phosphatase activity, which differed significantly from the
      findings in groups C and IT. In the same region, no difference was found between
      groups C and IT. In the distal small intestine, hypertrophy of villi and crypts
      (an adaptive response to the infection), coupled with an increase in enzymic
      activity, were present in both groups I and IT, in contrast to group C. These
      results suggest that a complete mucosal restoration occurred within 7 days of
      anthelmintic treatment in the parasitized part of the intestine. In contrast, the
      adaptive response observed beyond the main site of parasitism was not abolished
      by treatment. The functional significance of these findings is discussed in
      relation to the compensatory growth commonly observed after anthelmintic
      treatment in ruminants.

PMID- 8543672
TI  - Intestinal cellular immunity after primary rotavirus infection.
AB  - Infection of neonatal gnotobiotic lambs with a bovine strain of rotavirus was
      used to characterize the kinetics of the primary cellular intestinal immune
      response to this agent. At 2-3 days after infection virus was first detected in
      the faeces and increased numbers of CD45R+ cells were observed in peripheral
      blood. These cells persisted in significantly increased numbers in the
      circulation until 7-8 days after infection. At this time, virus was no longer
      detectable in the faeces. The increase in CD45R+ cells preceded the appearance of
      virus-neutralizing antibodies in the serum at 1 week after infection. Maximal
      antibody titres were reached 2 weeks after infection. Virus-primed cells were
      first observed 1 week after infection in the jejunal and ileal Peyer's patches,
      mesenteric lymph nodes and peripheral blood, and persisted in the mesenteric
      lymph nodes and jejunal Peyer's patches for a further 4 weeks. Analysis of
      lymphocyte surface antigens indicated that different sub-populations of
      lymphocytes were responding in the various lymphoid tissues; a majority of CD4+
      cells was observed in the mesenteric lymph nodes, whereas B cells predominated in
      the ileal Peyer's patches.

PMID- 8543673
TI  - Expression of beta 1 integrin in normal, dysplastic and neoplastic canine mammary
      gland.
AB  - The expression of beta 1 integrin was evaluated immunohistochemically in a series
      of normal, dysplastic and neoplastic canine mammary glands, and in lymph node
      metastases. The tissues were formalin-fixed and paraffin wax-embedded. In
      malignant neoplasms, beta 1 integrin was decreased and redistributed along the
      entire cell membrane. In lymph nodes, strong immunohistochemical staining was
      seen intercellularly in clusters of metastatic cells within subcapsular sinuses
      and at the periphery of intranodal metastases. These results suggest that the
      expression of integrin molecules may be related to malignancy and to the
      metastatic potential of neoplastic cells.

PMID- 8543674
TI  - A light microscopical, ultrastructural and immunohistochemical study of spindle
      cell adrenocortical tumours of ferrets.
AB  - Twelve adrenocortical tumours with a variable spindle-cell component in ferrets
      (six spayed females, three intact females, two castrated males, and one intact
      male) were examined by light microscopy. One tumour with a moderate spindle-cell
      component was examined ultrastructurally, and three tumours were studied
      immunohistochemically. Light microscopy revealed a spindle-cell component in the
      tumours that varied from a few such cells occupying the stroma between packets of
      adrenocortical cells to cells in such large numbers that they formed almost the
      entire substance of the tumour. By light microscopy these spindle cells resembled
      smooth muscle cells, and the ultrastructural findings, particularly the presence
      of thin contractile filaments, suggested that the spindle cells were of smooth
      muscle origin. Immunohistochemical staining revealed that the spindle cells were
      negative for cytokeratins and S-100 protein but positive for smooth muscle actin.
      Desmin was readily demonstrated in two tumours but not in the other examined.
      Vimentin was variable, generally producing a small to moderate amount of reaction
      product.

PMID- 8543675
TI  - Immunohistochemical analysis of the lymphoid organs of dogs naturally infected
      with canine distemper virus.
AB  - The pathogenesis of acute canine distemper in three naturally infected dogs was
      investigated. The lymphoid organs showed atrophy without secondary follicles. The
      distribution of canine distemper virus (CDV) antigens was examined
      immunohistochemically with monoclonal antibodies specific for canine Thy-1,
      immunoglobulin (Ig) M, CD4, CD8, CD21 and CD45RB, and anti-measles virus
      nucleocapsid protein serum. The viral antigens were located in the T-cell
      dependent areas and in the follicles of lymphoid organs; they were observed
      mainly in the Thy-1, or CD4-positive cells, but also in the CD8-, CD21-, or IgM
      positive cells. The results indicated that Thy-1-positive and CD4-positive T
      cells serve as major target cells for CDV during the acute stage of infection.

PMID- 8543676
TI  - An immunohistochemical study of the distribution of border disease virus in
      persistently infected sheep.
AB  - Three seronegative sheep persistently infected with Border disease virus and six
      seropositive, non-viraemic sheep were examined for the cellular distribution of
      the agent. These animals originated from a closed flock which had been kept in an
      isolation facility for 5 years. They were killed and immediately necropsied.
      There were no gross abnormalities other than reduced body weight of the
      persistently infected sheep. Two samples of each major organ were collected. The
      first sample was fixed by immersion in formalin and processed for histological
      examination, which showed no lesions unequivocally attributable to the viral
      infection. The second sample was snap-frozen for immunohistochemical examination.
      This revealed viral antigen in all organs of the persistently infected, but in
      none of the seropositive animals. The infected cells included smooth muscle cells
      of hollow organs and blood vessels, epithelial cells of the alimentary tract and
      urogenital organs, lymphocytes in lymphoid organs, endocrine cells, neurons and
      glial cell.

PMID- 8543677
TI  - Multiple piloleiomyomas in a cat.
AB  - The microscopical and immunohistochemical features of a rare cutaneous leiomyoma
      in a cat are described. The principal characteristics of this tumour were
      multiple bundles of smooth muscle, either discrete or conjoined, with numerous
      collagen fibres between the muscle cells, and osteoid metaplasia. The tumour was
      designated a piloleiomyoma as it was considered to have arisen from the arrector
      pili muscles.

PMID- 8543678
TI  - Lasers in dermatology.
AB  - The use of dermatologic laser therapy is rapidly expanding. Thirty years of
      experience has produced advances in the technology, techniques, and therapeutic
      efficacy of dermatologic lasers. The original lasers have been improved and
      modified, and new types of lasers have expanded the dermatologist's therapeutic
      repertoire. Extensive research has provided a greater understanding of the skin's
      clinical and histologic response to laser treatment. This has allowed
      dermatologists to expand their therapeutic options and techniques and to improve
      clinical outcome.

PMID- 8543679
TI  - Guidelines of care for superficial mycotic infections of the skin: mucocutaneous
      candidiasis. Guidelines/Outcome Committee. American Academy of Dermatology.

PMID- 8543680
TI  - Guidelines of care for superficial mycotic infections of the skin: onychomycosis.
      Guidelines/Outcomes Committee. American Academy of Dermatology.

PMID- 8543681
TI  - Guidelines of care for superficial mycotic infections of the skin: Piedra.
      Guidelines/Outcomes Committee. American Academy of Dermatology.

PMID- 8543682
TI  - Configuring for the World Wide Web: recommendations for dermatologists.
AB  - Physicians have become increasingly interested in obtaining the hardware,
      software, and connection necessary to take advantage of the educational and
      practice material available on the World Wide Web (WWW) (i.e., on the Internet).
      The related ongoing development of unique on-line resources promises to provide a
      compelling force for change in the way in which information is accessed and
      medicine is practiced. WWW applications created for dermatologists often include
      high-quality images, and proper viewing is critical to use this information.
      Because images tend to be large files, and dermatology resources tend to have
      from several up to hundreds of images, the speed of transfer and display and the
      quality of the display are important factors to consider. This study was an
      evaluation of some of the current options in the hardware, software, and Internet
      connections to determine desirable configurations for accessing image-rich, on
      line dermatology WWW applications.

PMID- 8543683
TI  - Surgical pearl: delayed knot placement facilitates small wound closure.

PMID- 8543684
TI  - Self-potentiating allergic contact dermatitis caused by doxepin hydrochloride
      cream.

PMID- 8543685
TI  - Plasma cell gingivitis: treatment with 2% fusidic acid.

PMID- 8543686
TI  - Multiple myeloma first presenting as cutaneous plasmacytoma.

PMID- 8543687
TI  - The useful plants of dermatology. II. Haematoxylum and hematoxylin.

PMID- 8543688
TI  - Zidovudine and psoriasis.

PMID- 8543689
TI  - Allergic contact dermatitis to tefillin.

PMID- 8543690
TI  - Case against antibiotic prophylaxis for endocarditis and prosthesis infection in
      dermatologic procedures involving uninfected skin.

PMID- 8543691
TI  - Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis
      in vitro and in vivo.
AB  - BACKGROUND: An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been
      described. However, AsA is quickly oxidized and decomposed in aqueous solution
      and thus is not generally useful as a depigmenting agent. OBJECTIVE: Our purpose
      was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC
      PMG), a stable derivative of AsA. METHODS: Percutaneous absorption of VC-PMG was
      examined in dermatomed human skin, and its effect on melanin production by
      mammalian tyrosinase and human melanoma cells in culture was also measured. A 10%
      VC-PMG cream was applied to the patients. RESULTS: VC-PMG suppressed melanin
      formation by tyrosinase and melanoma cells. In situ experiments demonstrated that
      VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours
      after application. The lightening effect was significant in 19 of 34 patients
      with chloasma or senile freckles and in 3 of 25 patients with normal skin.
      CONCLUSION: VC-PMG is effective in reducing skin hyperpigmentation in some
      patients.

PMID- 8543692
TI  - Influence of skin tension and formalin fixation on sonographic measurement of
      tumor thickness.
AB  - BACKGROUND: High-resolution sonographic measurement of skin tumors, especially of
      malignant melanomas, allows presurgical assessment of the most important
      prognostic factor--tumor thickness. A good correlation between ultrasonographic
      and histopathologic thickness measurement has been reported. Procedures for
      preparing tissue for histopathologic examination, such as excision, fixation in
      formalin, dehydration in alcohol, and embedding in paraffin, may cause the tissue
      to retract and shrink and may therefore affect thickness measurement results.
      OBJECTIVE: Our purpose was to evaluate the influence of skin preparation
      procedures on ultrasound measurement results and to compare tumor thickness
      values obtained sonographically versus those obtained histopathologically.
      METHODS: Sixty-three epithelial (n = 37) and melanocytic (n = 26) tumors, benign
      as well as malignant, were measured by ultrasound before and immediately after
      excision and after overnight fixation. Sonographically and histopathologically
      determined tumor thicknesses were compared. RESULTS: Loss of skin tension after
      excision led to an increase in measured tumor thickness because of spherical
      retraction of the specimen. Subsequent fixation, dehydration, and embedding
      reversed this effect, so that altogether, histopathologically assessed tumor
      thickness was only slightly lower than ultrasound-derived thickness before
      excision. This was true for melanocytic as well as epithelial lesions.
      CONCLUSION: Loss of skin tension after excision and tissue preparation procedures
      seem to offset each other and lead to a good overall correlation between
      ultrasonographic and histopathologic measurements.

PMID- 8543694
TI  - Sebaceous epithelioma: a review of twenty-one cases.
AB  - BACKGROUND: Sebaceous epithelioma is a benign tumor that must be differentiated
      from basal cell carcinoma and other appendageal tumors. OBJECTIVE: Histologic and
      clinical findings were reviewed in 21 patients with sebaceous epitheliomas.
      METHODS: Twenty-one cases of sebaceous epithelioma collected during a 5-year
      period were reviewed. RESULTS: The tumors appeared as yellow to flesh-colored
      papules, most often on the face and neck. They consisted of basaloid cells with
      foci of sebaceous differentiation. Cystic spaces formed by holocrine degeneration
      or simulating sebaceous duct lining were common findings. Patients with sebaceous
      epitheliomas were more likely than the general population to have an internal
      malignancy. CONCLUSION: Patients with sebaceous epithelioma should be examined
      for an underlying malignancy.

PMID- 8543693
TI  - Pemphigus herpetiformis is a rare clinical expression of nonendemic pemphigus
      foliaceus, fogo selvagem, and pemphigus vulgaris. Cooperative Group on Fogo
      Selvagem Research.
AB  - BACKGROUND: Pemphigus herpetiformis is a rare and atypical variant of pemphigus
      that resembles dermatitis herpetiformis. Most patients show antiepidermal
      autoantibodies that stain the epidermal intercellular spaces by
      immunofluorescence, similar to pemphigus autoantibodies, and lack the
      immunopathologic features of dermatitis herpetiformis. OBJECTIVE: The study was
      aimed at characterizing the specificity of the antiepidermal autoantibodies in
      seven patients with pemphigus herpetiformis. METHODS: The antiepidermal
      autoantibodies were characterized by immunofluorescence, immunoblotting, and
      immunoprecipitation studies in seven patients who fulfilled the clinical,
      histologic, and immunofluorescence diagnostic criteria for pemphigus
      herpetiformis. RESULTS: Five patients with features of pemphigus herpetiformis
      either had classic pemphigus foliaceus, or their disease evolved into classic
      pemphigus foliaceus. One of these patients had fogo selvagem. Two of the seven
      patients showed features of or had disease that evolved into pemphigus vulgaris.
      The antiepidermal autoantibodies present in all seven patients recognized
      desmoglein 1. CONCLUSION: Pemphigus herpetiformis is a rare clinical and
      histologic expression of nonendemic pemphigus foliaceus, fogo selvagem, and
      pemphigus vulgaris.

PMID- 8543695
TI  - Congenital nevomelanocytic nevi: proportionate area expansion during infancy and
      early childhood.
AB  - BACKGROUND: The way in which congenital nevomelanocytic nevi (CNN) expand
      relative to anatomic region during growth is relevant to decisions about optimal
      timing for surgical excision and assessment for malignant change. OBJECTIVE: Our
      purpose was to determine how CNN area expands relative to anatomic region during
      infancy and early childhood. METHODS: Forty-one small CNN in as many subjects
      were studied from the newborn period. Relative area (CNN area/anatomic region
      area) was derived for each measure. Proportionate expansion (PE), defined as
      change in relative area per unit time as a proportion of initial relative area,
      was calculated. Relative to anatomic region, area expansion of CNN is greater
      when PE is greater than 0, less when PE is less than 0, and at least double when
      PE is +1.0 or greater. RESULTS: From the newborn period to last measure (2 to 71
      months), PE ranged from -0.7 to +8.8 (median, +0.1). For 66% of CNN (27 of 41),
      PE was greater than 0. Nine of 39 CNN (15.4%) had PE values of +1.0 or greater
      during the first 6 months, compared with 1 of 26 cases (3.8%) for the interval
      beginning at or after 6 months. CONCLUSION: Disproportionately rapid area
      expansion of CNN may occur during early infancy, related to transient benign
      neoplasia, delayed pigmentation, and/or error of the methods used in the
      analysis.

PMID- 8543696
TI  - Clinical and histopathologic features of hair loss in patients with HIV-1
      infection.
AB  - BACKGROUND: Hair loss is common in patients with HIV-1 infection, and in black
      patients this loss may be associated with straightening. Possible causes are
      frequently present in patients with HIV-1. These causes include chronic HIV-1
      infection itself and recurrent secondary infections, nutritional deficiencies,
      immunologic and endocrine dysregulation, and exposure to multiple drugs. However,
      histopathologic features have rarely been reported in these patients. OBJECTIVE:
      The objective was to evaluate the changes in the hairs of a group of these
      patients and to identify the light microscopic and ultrastructural changes in the
      hairs and the histologic changes in the scalp. METHODS: Hair plucks and pulls
      with scanning electron microscopy of the hairs were done on 10 patients with late
      stage HIV-1 infection. In addition, scalp biopsy specimens were examined in both
      vertical and transverse sections. RESULTS: All patients had telogen effluvium.
      Numerous apoptotic or necrotic keratinocytes were seen in the upper external root
      sheath follicular epithelium in addition to a mild to moderate perifollicular
      mononuclear cell infiltrate often containing eosinophils. Variable dystrophy of
      the hair shafts was also a consistent feature. CONCLUSION: Although telogen
      effluvium is a common response to a wide spectrum of biologic stresses, the
      presence of apoptotic or necrotic keratinocytes within the upper end of the
      external root sheath epithelium and dystrophy of hairs may be markers of hair
      loss in patients with HIV-1 infection.

PMID- 8543697
TI  - Clinical and histologic spectrum of human T-cell lymphotropic virus type I
      associated lymphoma involving the skin.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is associated with infection
      with human T-cell lymphotropic virus type I (HTLV-I). OBJECTIVE: The objective
      was to describe the clinical, histopathologic, and immunologic features in three
      patients with ATL involving the skin. METHODS: Clinical histories and skin biopsy
      specimens were reviewed. Immunophenotypic studies were performed on peripheral
      blood lymphocytes (three patients) and on skin biopsy specimens (one patient).
      RESULTS: Serologic testing in each patient was positive for HTLV-I. Specific
      cutaneous lesions of ATL were diverse. Histologic features included markedly
      epidermotropic lymphoid infiltrates and dermal aggregates of lymphocytes and
      macrophages resembling granulomas. One patient died 3 months after diagnosis; the
      other two are alive with residual lymphoma. CONCLUSION: A spectrum of clinical,
      histologic, and immunophenotypic features are seen in ATL involving skin. Those
      cases with a chronic course may resemble mycosis fungoides clinically and
      histologically. Serologic testing for HTLV-I is recommended in all patients with
      cutaneous lymphoma from endemic areas and in those with other risk factors for
      HTLV-I infection.

PMID- 8543698
TI  - Folliculosebaceous cystic hamartoma: a clinical pathologic study.
AB  - BACKGROUND: Folliculosebaceous cystic hamartoma (FCH) is a recently recognized
      cutaneous hamartoma comprising follicular, sebaceous, and mesenchymal elements.
      Only nine cases have been previously reported. OBJECTIVE: The aim of this study
      was to characterize further the clinical, histologic, and immunohistologic
      features of FCH. METHODS: The clinical, histologic, and immunohistologic features
      of eight cases of FCH were evaluated and the literature reviewed. RESULTS: All
      lesions presented as exophytic papules or nodules on the head, most commonly the
      central part of the face. Age at onset ranged from 4 to 47 years. The size ranged
      from 0.5 x 0.4 cm to 1.4 x 1.1 cm. Clinical diagnoses were nevus, neurofibroma,
      and adnexal tumor. None of the patients had associated Muir-Torre syndrome. The
      diagnostic microscopic features of infundibular cystic structures with attached
      sebaceous glands and characteristic stroma were present in all lesions. Many of
      the stromal spindle cells were CD34 positive. CONCLUSION: FCH is a recently
      recognized hamartoma of follicular, sebaceous, and mesenchymal elements. Although
      reported only rarely, its incidence is likely much higher.

PMID- 8543699
TI  - Bleomycin-mediated electrochemotherapy of basal cell carcinoma.
AB  - BACKGROUND: A new technique, electroporation, enhances the antitumor effects of a
      variety of chemotherapeutic agents. When used in combination with conventional
      chemotherapy, the procedure is termed electrochemotherapy. Exposure of cancerous
      tissues to pulses of electricity during electrochemotherapy appears to increase
      cell membrane permeability and thus intracellular access to cytotoxic drugs.
      Electrochemotherapy has been shown to have potent antitumor activity in a variety
      of in vitro studies, animal tumor models, as well as in clinical trials with
      squamous cell carcinomas of the head and neck. OBJECTIVE: The purpose of the
      study was to determine the effects of bleomycin-mediated electrochemotherapy on
      several basal cell carcinomas (BCCs) in two patients with nevoid BCC syndrome.
      METHODS: Electrical pulses were delivered to tumor nodules by means of caliper
      electrodes after systemic doses of bleomycin were administered. Vital signs were
      closely monitored during application of the electrical pulses. RESULTS: Partial
      responses were observed in tumors from both of the patients treated with
      electrochemotherapy; three partial responses were observed in one patient, and
      one partial response was observed in the other patient. Complete responses were
      seen in two lesions. Only minimal local or systemic side effects were noted in
      response to the therapy. CONCLUSION: To our knowledge, this is the first study
      that documents the effects of bleomycin-mediated electrochemotherapy on BCC.
      Studies are ongoing with intralesional bleomycin during electrochemotherapy to
      see whether additional antitumour effects can be produced in patients with BCC by
      this route of administration.

PMID- 8543700
TI  - Hutchinson's sign: a reappraisal.
AB  - Hutchinson's sign, periungual extension of brown-black pigmentation from
      longitudinal melanonychia onto the proximal and lateral nailfolds, is an
      important indicator of subungual melanoma. However, experience has demonstrated
      that Hutchinson's sign, although valuable, is not an infallible predictor of
      melanoma. Periungual pigmentation is present in a variety of benign disorders
      and, therefore, may lead to overdiagnosis of subungual melanoma. Periungual
      hyperpigmentation occurs in at least one nonmelanoma skin cancer, Bowen's disease
      of the nail unit. Hyperigmentation of the nail bed and matrix may reflect through
      the "transparent" nailfolds simulating Hutchinson's sign. "Pseudo-Hutchinson's
      sign" is a phrase coined to encompass these three simulants of Hutchinson's sign.
      Each represents a misleading clue to the diagnosis of subungual melanoma. Total
      reliance on the (apparent) presence or absence of periungual pigmentation may
      lead to overdiagnosis or underdiagnosis of subungual melanoma. All relevant
      clinical and historical information, including the presence or absence of
      periungual pigmentation, must be carefully evaluated in a patient suspected of
      having subungual melanoma. Ultimately, the diagnosis of subungual melanoma is
      made histologically.

PMID- 8543701
TI  - The burning mouth syndrome.
AB  - The burning mouth syndrome is characterized by burning and painful sensations of
      the mouth in the absence of significant mucosal abnormalities. For patients in
      whom no causative factor can be identified, empiric antifungal, nutritional, and
      estrogen replacement therapy can be initiated. If these fail, long-term therapy
      with antidepressants, benzodiazepines, and clonazepam can be considered. Topical
      capsaicin and laser therapy have been reported beneficial in a few patients.

PMID- 8543702
TI  - Dermatologic drug formulary: an American Academy of Dermatology white paper.

PMID- 8543703
TI  - A randomized trial of self-help materials, personalized feedback, and telephone
      counseling with nonvolunteer smokers.
AB  - The incremental effects of (a) a self-help booklet alone, (b) self-help booklet
      with computer-generated personalized feedback, and (c) self-help booklet,
      personalized feedback, and outreach telephone counseling were evaluated in a
      population-based, nonvolunteer sample of smokers. Smokers (N = 1,137) were
      identified through a telephone survey of a random sample of 5,903 enrollees in a
      health maintenance organization and randomized to a no-treatment control group or
      1 of the 3 intervention conditions. Smoking status was ascertained 3, 12, and 21
      months postrandomization. Cotinine validation of self-reported cessation was
      obtained at the 12-month follow-up. Overall, the telephone counseling
      significantly increased smoking cessation at the 3-month follow-up, but not at 12
      or 21 months. Among smokers who were precontemplative at baseline, telephone
      counseling significantly increased prevalent abstinence at 3 and 12 months and
      continuous abstinence at 21 months (defined as self-reported abstinence at 3, 12,
      and 21 months).

PMID- 8543704
TI  - Stress and anxious-depressed symptoms among adolescents: searching for mechanisms
      of risk.
AB  - This study was an examination of the possible mechanisms of risk among
      adolescents (n = 55) exposed to the stress associated with the diagnosis of
      cancer in a parent. Girls whose mothers had cancer reported significantly more
      anxious-depressed symptoms than girls whose fathers were ill or boys whose
      mothers or fathers had cancer. Increased family responsibilities and the use of
      ruminative coping were examined as possible mechanisms leading to increased
      distress in girls with ill mothers. Although girls reported the use of more
      ruminative coping, rumination did not account for the impact of maternal cancer
      on girls' distress. Girls whose mothers were ill reported more stressful events
      reflecting family responsibilities. Furthermore, family responsibility stress
      fully accounted for the interaction of gender of the ill parent and gender of the
      adolescent in predicting anxious-depressed symptoms.

PMID- 8543705
TI  - Self-efficacy and marijuana cessation: a construct validity analysis.
AB  - Hypotheses regarding the relationships between self-efficacy for avoiding
      marijuana use and theoretically related measures were examined in a sample of 161
      men and 51 women who sought treatment aimed at marijuana cessation. Theoretically
      proposed sources of efficacy judgments showed stronger univariate and
      multivariate relationships with efficacy for avoiding marijuana use after
      treatment than before treatment. The cognitive-behavioral relapse prevention
      treatment resulted in marginally greater self-efficacy, compared with a
      nonbehavioral treatment, but the link between coping skill training and efficacy
      was ambiguous. Efficacy contributed incrementally to the prediction of
      posttreatment marijuana use beyond efficacy source variables, but it did not
      completely mediate the effects of those sources of efficacy judgments. Predictive
      validity was stronger for frequency of posttreatment marijuana use than for
      abstinence status. The need for better assessment of the efficacy construct and
      potential revisions in efficacy theory as applied to substance use are discussed.

PMID- 8543706
TI  - Objective and subjective factors in the disproportionate referral of children for
      academic problems.
AB  - R. S. Drabman, K. J. Tarnowski, and P. A. Kelly (1987) and K. J. Tarnowski, D. F.
      Anderson, R. S. Drabman, and P. A. Kelly (1990) examined children's month of
      birth in relation to referral for psychological services and found that younger
      children in the classroom were disproportionately referred for services. No
      differences were found between younger and older students on standardized
      measures of intelligence or academic achievement. Results of a replication and
      extension of these studies indicated (a) that younger children in the classroom
      were referred at a disproportionately higher rate, (b) that the referral pattern
      could not be explained by differences in children's competencies, (c) that
      Caucasian students were referred at disproportinately higher rates than minority
      students, and (d) a trend in which the proportionate referral rate of students as
      height or weight increased. Results are discussed within the context of teacher
      expectancies.

PMID- 8543707
TI  - Perceived benefit from child sexual abuse.
AB  - People often report perceptions of benefit from adverse life experiences. In this
      study, adult perceptions of benefit from child sexual abuse were examined in a
      sample of 154 low-income women who were sexually abused as children. Almost half
      reported some perceived benefit. The benefits fell into 4 main categories:
      protecting children from abuse, self-protection, increased knowledge of child
      sexual abuse, and having a stronger personality. Degree of perceived benefit was
      associated with several indicators of adult adjustment. In addition, those who
      perceived themselves as stronger had higher self-esteem, and those who perceived
      increased sexual abuse knowledge viewed others more favorably and were more
      comfortable getting close to others, when compared with other respondents.

PMID- 8543708
TI  - Five methods for computing significant individual client change and improvement
      rates: support for an individual growth curve approach.
AB  - Interest has been renewed in methods for determining individual client change.
      Currently, there are at least 4 pretreatment-posttreatment (pre-post) difference
      score methods. A 5th method, based on a random effects model and multiwave data,
      represents a growth curve approach and was hypothesized to be more sensitive to
      detecting significant (p < .05) change than the pre-post methods. The change
      rates produced by the 5 methods were compared in a sample of 73 older outpatients
      with 3 to 5 assessments per client on a measure of well-being (H. J. Dupuy,
      1977). Results indicated that the growth curve approach improvement rate was the
      highest (68.5%). The growth curve and the Edwards-Nunnally (63.0%) methods
      produced significantly (p < .05) higher improvement rates than the other 3
      methods, with 1 exception.

PMID- 8543709
TI  - Introduction to the special section on contemporary issues in human sexuality:
      research and practice.
AB  - Critical issues in human sexuality have changed markedly during the past decade
      and so have the contributions of psychology to the evaluation and treatment of
      sexual behavior problems. Some of the greatest challenges facing psychologists
      today include the increasing emphasis on medical interventions for the male
      sexual disorders and the relative decline of traditional behavioral sex
      therapies, the recalcitrance of sexual desire disorders, the prevention of
      "unsafe" sexual behavior, and the limited understanding of female sexuality. This
      overview introduces a series of 5 articles that examine these selected critical
      issues in human sexuality. Guidelines for clinical practice and directions for
      future research are highlighted.

PMID- 8543710
TI  - Psychology's role in the assessment of erectile dysfunction: historical
      precedents, current knowledge, and methods.
AB  - This article describes the role of the psychologist in the evaluation of erectile
      dysfunction. It begins by reviewing current diagnostic criteria and providing a
      historical overview. Next, current epidemiologic knowledge is summarized,
      including data on prevalence and recent research examining cognitive, affective,
      dyadic, and lifestyle etiologic risk factors. This is followed by a state-of-the
      science discussion of assessment procedures. Recent psychophysiologic methods are
      highlighted, including RigiScan monitoring, waking arousal, and diurnal
      tumescence. It concludes by emphasizing the necessity of continued collaboration
      between psychology and medicine for both evaluation and treatment.

PMID- 8543711
TI  - Treatment of sexual disorders in the 1990s: an integrated approach.
AB  - Marked changes have occurred in the formulation and treatment of sexual disorders
      in the past 2 decades. Emphasis has shifted to the role of biomedical and organic
      factors in the etiology of sexual dysfunction, along with the growing use of
      medical and surgical treatment interventions. Multidimensional assessment models
      are widely used, particularly in the evaluation of male erectile dysfunction and
      sexual pain disorders. Integrated treatment approaches have also been developed,
      as cognitive-behavioral and couples' therapy procedures are increasingly combined
      with traditional sex therapy techniques. This article reviews existing data
      regarding the etiology and treatment of male and female sexual dysfunctions.
      Despite the conceptual and technological sophistication of current approaches,
      treatment outcome is less than satisfactory in several areas. Further research is
      needed on the etiology and treatment of sexual disorders.

PMID- 8543713
TI  - Increased attention to human sexuality can improve HIV-AIDS prevention efforts:
      key research issues and directions.
AB  - Curtailing the human immunodeficiency virus (HIV) epidemic requires the
      development of effective strategies for helping people reduce high-risk sexual
      behavior patterns. Because the objective of HIV prevention involves changing how
      people behave sexually, research findings in human sexuality are extremely
      pertinent to efforts to promote AIDS risk reduction. Unfortunately, most public
      health HIV prevention programs rarely reflect findings of human sexuality
      research. In this article, research is reviewed in the areas of the relationship
      contexts of sexuality, including variations in monogamy, condom use in
      affectionate versus casual relationships, sexual communication, and coercion; the
      modification of sexual behavior repertoires; substance use in relation to sexual
      intercourse; and sexual schema and scripts relevant to HIV risk. Policy and
      training issues related to human sexuality may have hindered efforts to
      incorporate sexuality research findings in HIV prevention programs. Advances and
      refinements in the success of HIV prevention efforts are likely if research on
      human sexuality is better integrated in AIDS prevention programs.

PMID- 8543714
TI  - Hypoactive sexual desire disorder: an overview.
AB  - This article reviews the current state of knowledge about hypoactive sexual
      desire disorder (HSDD). Despite considerable clinical attention that has been
      given to this disorder, ambiguity remains concerning the nature and treatment of
      low sexual desire. This article reviews diagnostic issues, including prevalence
      estimates. Current theories of etiology and maintenance are highlighted, as well
      as available assessment strategies. Controlled treatment studies are reviewed,
      with particular focus on the need to develop desire-specific interventions.
      Throughout this review, areas where additional work is needed are highlighted.

PMID- 8543712
TI  - Women's sexuality: behaviors, responses, and individual differences.
AB  - Classic and contemporary approaches to the assessment of female sexuality are
      discussed. General approaches, assessment strategies, and models of female
      sexuality are organized within the conceptual domains of sexual behaviors, sexual
      responses (desire, excitement, orgasm, and resolution), and individual
      differences, including general and sex-specific personality models. Where
      applicable, important trends and relationships are highlighted in the literature
      with both existing reports and previously unpublished data. The present
      conceptual overview highlights areas in sexual assessment and model building that
      are in need of further research and theoretical clarification.

PMID- 8543715
TI  - Eye movement desensitization and reprocessing (EMDR) treatment for
      psychologically traumatized individuals.
AB  - The effects of 3 90-min eye movement desensitization and reprocessing (EMDR)
      treatment sessions on traumatic memories of 80 participants were studied.
      Participants were randomly assigned to treatment or delayed-treatment conditions
      and to 1 of 5 licensed therapists trained in EMDR. Participants receiving EMDR
      showed decreases in presenting complaints and in anxiety and increases in
      positive cognition. Participants in the delayed-treatment condition showed no
      improvement on any of these measures across the 30 days before treatment, but
      after treatment participants in the delayed-treatment condition showed similar
      effects on all measures. The effects were maintained at 90-day follow-up.

PMID- 8543716
TI  - Depressed mood in Chinese children: relations with school performance and family
      environment.
AB  - A sample of primary school children in Shanghai, People's Republic of China,
      participated in this 2-year longitudinal project. Information on the family
      environment, children's social functioning, academic achievement, and depression
      was collected from multiple sources. The mean depression scores in the Chinese
      children was found to be similar to those found for children in the West.
      Depression was positively associated with aggressive-disruptive behavior and
      negatively associated with social competence. School social and academic
      difficulties were concurrently and positively correlated with depression.
      Moreover, social adjustment problems at age 8 were associated with depression at
      age 10. Academic difficulties were predictive of later depression only for
      children from families in which the mother was rejecting and parents had a
      conflictual relationship. Finally, decline in social and academic performance was
      related to depressed affect.

PMID- 8543717
TI  - Evaluation of a brief cognitive-behavioral program for the prevention of chronic
      PTSD in recent assault victims.
AB  - The efficacy of a brief prevention program (BP) aimed at arresting the
      development of chronic PTSD was examined with 10 recent female victims of sexual
      and nonsexual assault who received 4 sessions of a cognitive-behavioral program
      shortly after the assault. Their PTSD and depression severity was compared with
      that of 10 matched recent female assault victims who received repeated
      assessments of their trauma-related psychopathology (assessment control; AC). The
      BP program consisted of education about common reactions to assault and cognitive
      behavioral procedures. Two months postassault, victims who received the BP
      program had significantly less severe PTSD symptoms than victims in the control
      condition; 10% of the former group met criteria for PTSD versus 70% of the latter
      group. Five and a half months postassault, victims in the BP group were
      significantly less depressed than victims in the AC group and had significantly
      less severe reexperiencing symptoms.

PMID- 8543718
TI  - Rorschach and MMPI-2 indices of early psychotherapy termination.
AB  - This study was an investigation of the differences between 97 patients who had
      prematurely terminated psychotherapy (M = 1 session) and 81 who had participated
      in individual psychotherapy for at least 6 months and 24 sessions (M = 18
      months/72 sessions) on selected Minnesota Multiphasic Personality Inventory--2
      (MMPI-2) and Rorschach variables. None of the between-group comparisons using the
      MMPI-2 proved to be significant. However, a multivariate analysis of variance of
      9 Rorschach variables in 3 conceptual categories--(a) interpersonal relatedness,
      (b) psychological resources versus resource demand, and (c) level of
      psychopathology--proved to be significant at p = .008. The Rorschach scores from
      the interpersonal-relational category proved to be the most robust in
      differentiating the 2 groups. The theoretical implications of interpersonal
      variables are discussed in relation to the termination and continuation of
      patients in psychotherapy.

PMID- 8543719
TI  - Researcher allegiance and meta-analysis: the case of cognitive therapy for
      depression.
AB  - K. S. Dobson (1989) conducted a meta-analysis of 28 studies of cognitive
      behavioral therapy for depression that used the Beck Depression Inventory as
      outcome measure. He concluded that the outcome of this type of therapy was
      superior to that of other forms of psychotherapy and to that of pharmacotherapy.
      The present study reanalyzed the same studies, and a further set of 37 similar
      ones published from 1987 to 1994, taking into account variations in sample size
      and researcher allegiance. This study confirmed Dobson's conclusions for his
      original sample but showed that about half the difference between CT and other
      treatments was predictable from researcher allegiance. However, comparable
      analyses of the later set of studies showed no effect of researcher allegiance.
      Two causes for these phenomena are (a) a historical effect, whereby both effect
      sizes and allegiance were large in earlier years and declined over time and (b) a
      treatment effect whereby effect size and allegiance were correlated, but more for
      some treatments than others. This correlation has also weakened over time.

PMID- 8543720
TI  - Frequency and correlates of posttraumatic-stress-disorder-like symptoms after
      treatment for breast cancer.
AB  - Diagnosis of life-threatening illness now meets Diagnostic and Statistical Manual
      of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994)
      criteria for traumatic stressor exposure for posttraumatic stress disorder
      (PTSD). Quality of life (QOL) and PTSD-like symptoms were assessed in 55 women
      posttreatment for breast cancer. PTSD symptom measures included the PTSD
      Checklist--Civilian Version (PCL-C) and the Impact of Events Scale. QOL was
      assessed using the 20-item Medical Outcomes Study Questionnaire. PTSD
      symptomatology was negatively related to QOL, income, and age. Time since
      treatment, type of cytotoxic treatment, and stage of disease were unrelated to
      PTSD symptoms. With suggested criteria for the PCL-C, 5% to 10% of the sample
      would likely meet DSM-IV PTSD criteria. Findings suggest that in survivors of
      breast cancer, these symptoms might be fairly common, may exceed the base rate of
      these symptoms in the general population, are associated with reports of poorer
      QOL, and, therefore, warrant further research and clinical attention.

PMID- 8543721
TI  - Los Angeles County after the 1992 civil disturbances: degree of exposure and
      impact on mental health.
AB  - The impact of the 1992 Los Angeles (L.A.) civil disturbances on psychosocial
      functioning was assessed as part of a larger project investigating the views and
      attitudes of residents in L.A. County. Random digit dialing methodology
      identified a household probability sample of 1,200 adults (age 18 or older) from
      L.A. County. Respondents completed a telephone interview 6 to 8 months after the
      disturbances. Respondents' degree of exposure to the disturbances, mental health
      impact of the disturbances, and mental health effects of chronic versus acute
      exposure to violence were assessed. Consistent with hypotheses, the impact of the
      disturbances was the worst in the South Central communities. Higher rates of
      posttraumatic stress disorder (PTSD; both diagnostic level and subclinical
      symptomatology) were found among respondents who reported disturbance-related
      experiences. Exposure to an acute event (i.e., the disturbances) was predictive
      of current PTSD symptomatology after controlling for demographics, lifetime
      trauma, and other types of stressful events.

PMID- 8543722
TI  - Impact of Cluster C personality disorders on outcomes of contrasting brief
      psychotherapies for depression.
AB  - Twenty-seven of 114 depressed clients, stratified for severity of depression,
      obtained a Diagnostic and Statistical Manual of Mental Disorders (3rd ed.; DSM
      III; American Psychiatric Association, 1980) diagnosis of Cluster C personality
      disorder--that is, avoidant, obsessive-compulsive or dependent personality
      disorder (PD clients)--whereas the remaining 87 did not (non-personality-disorder
      [NPD] clients). All clients completed either 8 or 16 sessions of cognitive
      behavioral (CB) or psychodynamic-interpersonal (PI) psychotherapy. On most
      measures, PD clients began with more severe symptomatology than NPD clients.
      Among those who received PI therapy, PD clients maintained this difference
      posttreatment and at 1-year follow-up. Among those who received CB therapy,
      posttreatment differences between PD and NPD groups were not significant.
      Treatment length did not influence outcome for PD clients. PD clients whose
      depression was also relatively severe showed significantly less improvement after
      treatment than either PD clients with less severe depression or NPD clients.

PMID- 8543723
TI  - Barriers to condom use among heterosexual male and female college students.
AB  - The authors used a questionnaire to assess gender differences in barriers to
      condom use among 198 female and 89 male heterosexual undergraduate college
      students. Participants were divided into three groups--consistent users,
      inconsistent users, and nonusers--based on their reported condom use. Factor
      analyses on each gender revealed similar barrier factor structures, but the
      barriers explained more of the variance in condom use among women than among men.
      Of the 9 or 10 predictors assessed, the low perceived need barrier was the most
      powerful predictor of condom use for both genders. Male and female participants
      who were nonusers, in a current monogamous relationship, and using oral
      contraceptives were more likely to report a low perceived need to use condoms.
      Implications for future research are discussed.

PMID- 8543724
TI  - College students' sexual attitudes and behaviors: implications for sexuality
      education.
AB  - This study of sexual attitudes and behaviors of students in a large northeastern
      community college was undertaken in partial response to an outspoken community
      group's claims that the sexuality education courses being taught at the school
      were undermining the morality of its young adults and encouraging early sexual
      activity. Findings from 1,825 pretest respondents in human sexuality and general
      health courses indicated that more than 80% of the students had experienced
      sexual intercourse before they took the courses. In a posttest comparison with
      1,456 of the same students, the authors found no significant changes in the
      number of students who were sexually active or in their attitudes about such
      issues as abortion and premarital, casual, or oral sex. Statistically significant
      changes did occur in human sexuality students' attitudes and behaviors about
      safer sex, having fewer sex partners, and using condoms and spermicides.

PMID- 8543725
TI  - Establishing a college health service in a College of Nursing.
AB  - College health services traditionally have been aligned with student affairs or
      student service areas. The author describes the evolution of a college health
      service as it moved from a College of Medicine to a College of Nursing on a
      health science campus. Alignment with student affairs exists; however, the formal
      reporting mechanism and budget are based in the College of Nursing. Contributions
      to the success of the operation and challenges it faced are discussed.

PMID- 8543727
TI  - The relation of exercise habits to health beliefs and knowledge about
      osteoporosis.
AB  - The relation of exercise habits of 113 female college students to their knowledge
      about osteoporosis and their health beliefs was investigated, using the health
      belief model to determine why some people participate in self-care preventive
      actions but others do not. Age was positively correlated with the level of
      osteoporosis knowledge, awareness of personal susceptibility, and motivation for
      general health behaviors. Older participants, however, perceived more barriers to
      exercise as an osteoporosis-prevention measure than did the younger respondents.
      The authors' conclusions support the importance of early osteoporosis education
      and lifetime physical activities to prevent osteoporosis.

PMID- 8543726
TI  - Common hand warts in athletes: association with trauma to the hand.
AB  - Forty-nine members of a university track team and 80 members of the crew team
      were surveyed about warts on their hands. They were also questioned about the
      nature and extent of their exercise, the types of equipment they used, and
      whether they wore protective gloves. Common hand warts were significantly more
      prevalent in members of the crew team than in members of the track team (25% v
      10%; p < .05). Although both groups lifted weights regularly, the crew team
      members were less likely to use protective gloves; they sustained additional
      trauma to their hands from almost daily exercise on rowing machines and river
      practice. College health providers should question patients with hand warts about
      types of athletic activity and should suggest that they protect their hands by
      wearing weight-lifter's gloves.

PMID- 8543728
TI  - Health center 2000: the mission development challenge.
AB  - College and university health centers are facing a dynamic era of change. In
      fact, change is the constant that permeates the organization. The one essential
      ingredient to dealing most effectively with change is to have a clearly defined
      mission. The author outlines a seven-step process that can be used by college and
      university health center personnel to create, reaffirm, and/or revise their
      mission statements, which serve as a beacon for decision making, organizational
      culture, and responsible action.

PMID- 8543729
TI  - Choosing without losing: resisting medical heterosexism.

PMID- 8543730
TI  - Do somatic complaints mask negative affect in youth?
AB  - The developmental transition between adolescence and early adulthood represents a
      high-risk period for the onset of somatization. Although research has lagged
      clinical work in this area, it has long been believed that, for somatizing youth,
      physical complaints are best conceptualized as a defense against negative affect.
      Recent adult-oriented research, however, suggests that somatic complaints may be
      better conceptualized on a continuum, with physical complaints covarying with
      overt psychological symptomatology. To explore these hypotheses systematically,
      the authors studied the relationship between multiple dimensions of psychological
      distress and somatic complaints in undergraduate students. Higher levels of
      physical symptom reporting were associated with complaints of more overt
      psychological distress, a finding that was consistent with a continuum
      perspective. The implications of these results for understanding somatization in
      college student populations and for university-based healthcare are discussed.

PMID- 8543731
TI  - Beyond performance enhancement: polypharmacy among collegiate users of steroids.
AB  - The extremely low prevalence of steroid use among college students makes it
      virtually impossible to conduct analyses on any single college campus. By
      studying a cohort of 58,625 college students from 78 institutions that
      administered the Core Alcohol and Drug Survey in 1990 and 1991, a critical mass
      of 175 users on which it was possible to conduct statistical analyses was
      identified. Compared with a randomly selected group of nonusers, the steroid
      users reported consuming dramatically more alcohol and demonstrated higher rates
      of binge drinking. In addition, a significantly higher percentage of steroid
      users reported using tobacco, marijuana, cocaine, amphetamines, sedatives,
      hallucinogens, opiates, inhalants, and designer drugs. A higher percentage of
      steroid users than nonusers also reported experiencing negative consequences as a
      result of substance abuse, and a greater percentage of the steroid users reported
      family histories of abuse of alcohol and other drugs. Implications from the
      standpoint of student development are discussed.

PMID- 8543732
TI  - Ciprofloxacin desensitization in a patient with cystic fibrosis.

PMID- 8543733
TI  - Hemodialysis-induced rash: a unique case of cholinergic urticaria.

PMID- 8543734
TI  - Royal jelly-induced asthma and anaphylaxis: clinical characteristics and
      immunologic correlations.

PMID- 8543735
TI  - Assessment of the endogenous allergens in glyphosate-tolerant and commercial
      soybean varieties.

PMID- 8543736
TI  - Removal of mite allergens from blankets: comparison of dry cleaning and hot water
      washing.

PMID- 8543737
TI  - Inhaled beta 2-agonists and allergen-induced airway responses.

PMID- 8543738
TI  - Try using binoculars.

PMID- 8543739
TI  - Cromolyn metered dose inhaler.

PMID- 8543740
TI  - Comments on the 1995 Presidential address.

PMID- 8543741
TI  - Gender risk for anaphylactoid reactions to contrast material.

PMID- 8543742
TI  - Discussion of risk of scuba diving in individuals with allergic and respiratory
      diseases: SCUBA Subcommittee.

PMID- 8543743
TI  - Normal diurnal variation in serum cortisol concentration in asthmatic children
      treated with inhaled budesonide.
AB  - BACKGROUND: Twenty-four-hour serum cortisol secretion is a sensitive parameter
      for the assessment of the pituitary-adrenal function of asthmatic children
      treated with inhaled corticosteroids. This study was undertaken to determine the
      effect of the long-term administration of inhaled budesonide on 24-hour cortisol
      production in young children with asthma. METHODS: We studied 11 children, aged 7
      to 12 years, with severe perennial asthma. All had been receiving 100 micrograms
      of inhaled budesonide twice daily, administered with a spacer device, for 3 to 5
      years. Serum cortisol concentration was measured at 8:00 A.M., 60 minutes after
      intravenous administration of 0.25 mg of corticotropin, and every 30 minutes for
      24 hours in an open-design study. Urinary cortisol secretion was measured by 24
      hour urine collection. All determinations were made with a radioimmunoassay kit.
      RESULTS: The individual morning serum cortisol concentration and the serum
      cortisol concentration at 60 minutes after corticotropin stimulation were within
      normal limits in all children. The 24-hour urinary cortisol excretion was also
      normal. The individual 24-hour serum cortisol concentration showed a normal
      pattern in all children, with no evidence of nocturnal suppression of serum
      cortisol concentration. CONCLUSION: Prolonged (3 to 5 years) administration of
      200 micrograms/day of inhaled budesonide in young children with severe asthma
      does not impair pituitary-adrenal function, even according to the sensitive test
      for 24-hour serum cortisol secretion.

PMID- 8543744
TI  - Long-term follow-up of patients treated with a three-year course of cat or dog
      immunotherapy.
AB  - BACKGROUND: A 5-year follow-up study was conducted to investigate the duration of
      the effects of a 3-year course of immunotherapy with standardized cat or dog
      extracts in 32 children and adults with asthma caused by animal dander. METHODS:
      Thirty of the subjects could be reached with a questionnaire, 19 underwent
      bronchial allergen and histamine challenges, and four had only a histamine
      challenge. Specific IgE and IgG4 levels in serum were measured in those who
      underwent challenges. RESULTS: Almost all subjects (26 of 30) reported no change
      (17 subjects) or increased tolerance (9 subjects) on exposure to cats or dogs. In
      contrast, 17 of the 19 who underwent allergen challenges had increased allergen
      sensitivity compared with when therapy was stopped (p < 0.01), and the results
      were no longer significantly different from before therapy was started. Mean
      provocative concentration of histamine causing a 20% fall in peak expiratory flow
      was, however, still higher than before therapy in the cat immunotherapy group (p
      < 0.01) and had not changed significantly during the follow-up period. In the dog
      immunotherapy group there was no significant change during or after therapy.
      Specific IgG4 had decreased, and specific IgE in serum had remained low and was
      comparable to the levels measured at the end of the study period. CONCLUSIONS:
      Five years after stopping immunotherapy, objectively measured bronchial allergen
      sensitivity had increased and had approached pretreatment conditions. Asthma
      symptoms, according to patients' subjective evaluations, had continued to be mild
      in most patients, and bronchial histamine sensitivity had remained stable. These
      observations could reflect remaining effects of immunotherapy or the natural
      history of mild asthma.

PMID- 8543745
TI  - A low allergen diet is a significant intervention in infantile colic: results of
      a community-based study.
AB  - BACKGROUND: The effect of diet change in 38 bottle-fed and 77 breast-fed
      "colicky" infants, referred from community-based pediatric facilities was studied
      over a 1-week period in a double-blind (within each feeding mode), randomized,
      placebo-controlled trial. METHODS: Bottle-fed infants were assigned to either
      casein hydrolysate or cow's milk formula. All mothers of breast-fed infants were
      started on an artificial color-free, preservative-free, additive-free diet and
      also randomized to an active low allergen diet (milk-, egg-, wheat-, nut-free) or
      a control diet. RESULTS: The response to diet was assessed on day 1 and day 8
      with the use of a previously validated infant distress chart on which parents
      recorded distress levels. If successful outcome was defined as a reduction in
      distress of 25% or more, after adjusting for age and feeding mode, infants on
      active diet had a significantly higher rate of improvement than those on the
      control diet (odds ratio, 2.32; 95% confidence interval, 1.07-5.0; p = 0.03).
      Analysis of the day 8 to day 1 distress ratio, again adjusted for age and feeding
      mode, showed that infants on the active diet had distress reduced by 39% (95%
      confidence interval, 26-50) compared with 16% (95% confidence interval, 0-30) for
      those on the control diet (p = 0.012). CONCLUSION: The results suggest a period
      of dietary modification with a low allergen diet and appropriate nutritional
      support should be considered in healthy infants with colic.

PMID- 8543746
TI  - Undifferentiated somatoform idiopathic anaphylaxis: nonorganic symptoms mimicking
      idiopathic anaphylaxis.
AB  - BACKGROUND: Northwestern University's Division of Allergy and Immunology has had
      experience with the diagnosis and treatment of more than 350 patients with
      idiopathic anaphylaxis (IA). In 1992 we reported a group of patients with IA
      whose presentations mimicked IA, but IA and other organic causes were later
      excluded. Psychologic factors were suspected as the underlying problem. These
      patients were classified as IA-variant. Management of these cases was extremely
      difficult. There was significant morbidity and high and unnecessary costs.
      OBJECTIVE: We aim to distinguish the nature of this disease and to highlight the
      evaluation and treatment of this group of patients. METHODS: Their cases are
      reviewed and reported. RESULTS: Common features included (1) presenting symptoms
      mimicking IA, (2) no objective findings that correlated with 1, (3) no response
      to the therapeutic regimen for IA, (4) meeting the Diagnostic and Statistical
      Manual of Mental Disorders criteria for undifferentiated somatoform disorder, and
      (5) significant wasted health care expenditure. CONCLUSIONS: This group of
      patients were better defined as having undifferentiated somatoform-IA. An
      algorithm was proposed to expedite the diagnosis of the disease so that with
      early recognition of the disease, unwarranted repetitive consultations, tests,
      and inappropriate therapy can be avoided.

PMID- 8543747
TI  - Resolution of chronic urticaria in patients with thyroid autoimmunity.
AB  - BACKGROUND: Autoimmune disease has been implicated as a cause of chronic
      urticaria, and anti-thyroid antibodies have been found in patients with chronic
      urticaria. Because some patients with chronic urticaria and autoimmune
      hypothyroidism have had clinical resolution with thyroid hormone replacement, we
      investigated the effect of thyroid hormone in euthyroid patients with chronic
      urticaria and thyroid autoimmunity. METHODS: Ten euthyroid patients with
      refractory hives were treated with thyroxine. Seven patients had elevated anti
      thyroid antibodies at baseline. Thyroid function and anti-microsomal and anti
      thyroglobulin antibody levels were monitored during treatment. If a clinical
      response was achieved, thyroxine was discontinued and restarted if symptoms
      recurred. RESULTS: Seven patients with elevated anti-thyroid antibodies reported
      resolution of symptoms within 4 weeks. Three patients without elevated anti
      thyroid antibodies did not respond. Five patients had a recurrence of symptoms
      after treatment was stopped, which resolved after treatment was restarted.
      Thyroid-stimulating hormone levels decreased in all patients with a clinical
      response. No correlation between clinical resolution and anti-thyroid antibody
      levels was seen. CONCLUSION: Thyroid autoimmunity in euthyroid patients may be
      associated with chronic urticaria, and treatment with thyroid suppression can
      result in clinical remission.

PMID- 8543748
TI  - The preventive effect and duration of action of two doses of inhaled furosemide
      on exercise-induced asthma in children.
AB  - BACKGROUND: Exercise-induced asthma can be prevented by treatment with inhaled
      furosemide. OBJECTIVE: In this study we evaluated the effect and duration of
      action of two doses (15 and 30 mg) of inhaled furosemide in prevention of
      exercise-induced asthma in children. METHODS: Ten children with exercise-induced
      asthma (8 boys and 2 girls, aged 6 to 13 years) were included in the study. Each
      patient was tested with three treatment regimens (placebo, 15 mg of furosemide,
      and 30 mg of furosemide) in random order on 3 separate days. Patients performed
      exercise challenges on a treadmill at 20 minutes and 1, 2, 3, and 6 hours after
      each treatment. Pulmonary function, urinary output, and fluid intake were
      monitored. RESULTS: Both doses of furosemide had a significantly greater
      protective effect than placebo, but there was no significant difference between
      the two doses of furosemide. The higher dose of furosemide was associated with
      increased urinary output and had a longer duration of action. CONCLUSION: A 30 mg
      dose of furosemide is more effective for treatment of exercise-induced asthma in
      terms of duration but has a significant diuretic effect.

PMID- 8543749
TI  - Histamine N-methyltransferase inhibitor potentiates histamine- and antigen
      induced airway microvascular leakage in guinea pigs.
AB  - BACKGROUND: Histamine N-methyltransferase (HMT) modulates histamine- and antigen
      induced bronchoconstriction. However, it is unclear whether vascular permeability
      evoked by an allergic reaction can be exaggerated by inhibition of HMT activity.
      METHODS: We studied the effects of intravenously injected SKF 91488, a specific
      HMT inhibitor, on increases in plasma extravasation induced by intravenously
      injected histamine in unsensitized guinea pigs and by intravenously injected
      ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue
      dye as a marker. RESULTS: Pretreatment with SKF 91488 shifted, in a dose
      dependent fashion, the dose-response curves of the leakage of dye to histamine to
      lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise,
      pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the
      leakage of dye induced by ovalbumin antigen (200 micrograms/kg intravenously) in
      three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously
      injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg
      intravenously), did not alter the leakage of dye induced by histamine (from 0.001
      microgram/kg to 10 micrograms/kg intravenously) (p < 0.20). HMT activities were
      observed in the nasal mucosa, as well as in the trachea and main bronchi, as
      shown in a previous study. CONCLUSION: These findings suggest that HMT modulates
      the effects of exogenous histamine and endogenously released histamine induced by
      antigen challenge on plasma extravasation in the airway in guinea pigs in vivo.

PMID- 8543750
TI  - Development of immune response to cow's milk proteins in infants receiving cow's
      milk or hydrolyzed formula.
AB  - BACKGROUND: Development of humoral and cellular immune responses to orally
      administered antigens in human beings is poorly understood, although antigen
      administration has been suggested as a treatment for hypersensitivity disorders
      and autoimmune diseases. OBJECTIVE: The purpose of the study was to investigate
      the development of systemic immune response in infants fed with formula
      containing whole cow's milk proteins or hydrolyzed formula containing casein
      peptides. METHODS: In a double-blind trial, 10 infants received cow's milk-based
      formula, and 10 infants received a casein hydrolysate formula until the age of 9
      months. Blood samples were taken at the ages of 6, 9, and 12 months. Cellular
      responses were assessed by proliferation assay of peripheral blood mononuclear
      cells to cow's milk proteins (beta-lactoglobulin, bovine serum albumin, and alpha
      casein). Humoral responses to the same proteins were measured by ELISA for IgG
      antibodies. RESULTS: Feeding infants with cow's milk-based formula induced
      systemic humoral and cellular responses to cow's milk proteins. T-cell response
      later declined, supporting the concept of oral tolerization. Exposure to cow's
      milk proteins after the age of 9 months resulted in depressed cellular and
      humoral responsiveness to these proteins. CONCLUSION: Our results support the
      view that induction of oral tolerance in human beings is an age-dependent
      phenomenon.

PMID- 8543751
TI  - Human nasal mucosal carboxypeptidase: activity, location, and release.
AB  - BACKGROUND: Carboxypeptidases (CPs), such as carboxypeptidase N (CPN) (kininase
      I, E.C.3.4.17.3), may regulate peptide-mediated vasodilation and vascular
      permeability in respiratory mucosa by degrading proinflammatory peptides such as
      bradykinin, anaphylatoxins, and neuropeptides during allergic and nonallergic
      inflammation. The sources of CP activity in human nasal secretions were
      investigated. METHODS: Well-characterized human nasal provocation and secretion
      analysis methods were used. Potential sources of CPN in human nasal mucosa were
      identified by immunohistochemistry. CP activity was defined as DL-2
      mercaptomethyl-3-guanidinoethylthiopropanoic acid inhibitable Bz-Gly-Lys
      degradation. CP activity was measured in nasal mucosal homogenates and nasal
      lavage fluids induced by methacholine, histamine, and allergen nasal provocation.
      RESULTS: CPN-immunoreactive material was localized to the glycocalyx of the
      epithelium, some vessels, and gland ducts near the epithelial basement membrane
      but not to submucosal gland cells. CP activity in human nasal lavage fluid after
      saline nasal provocation was 0.10 +/- 0.04 U/L. Histamine provoked secretion of
      significantly more CP activity (3.84 +/- 0.99 U/L; p < 0.01 vs saline).
      Methacholine did not significantly increase secretion (0.54 +/- 0.22 U/L). After
      nasal allergen challenge, CP activity was at a maximum between 11 and 20 minutes,
      and CP activity correlated with IgG concentration (r = 0.91, p < 0.01), a marker
      for proteins of plasma origin, suggesting that CP activity originated in plasma.
      CONCLUSIONS: These data suggest that plasma is the predominant source of CP
      activity secreted from human nasal mucosa and that plasma extravasation and
      interstitial fluid exudation across the epithelium are the primary processes
      regulating its appearance in nasal secretions.

PMID- 8543752
TI  - Seasonal variations of interleukin-4 and interferon-gamma release by peripheral
      blood mononuclear cells from atopic subjects stimulated by polyclonal activators.
AB  - IgE synthesis is controlled by interleukin (IL)-4 and interferon (IFN)-gamma, but
      there is heterogeneity in the IL-4 response depending on the sensitization of
      patients and natural allergen exposure. In patients sensitized to various
      allergens, we studied the synthesis of IL-4, IFN-gamma, and IgE to determine to
      what extent their in vitro immune response may be influenced by pollen season,
      depending on their sensitization. We studied 12 nonallergic individuals, seven
      patients sensitized to cypress pollen, 12 sensitized to grass pollen, 14
      sensitized to several pollens, and 42 patients with polysensitization. The
      release of IL-4 and IFN-gamma from peripheral blood mononuclear cells stimulated
      by polyclonal agents (calcium ionophore A23187 and phorbol myristate acetate) was
      measured by ELISA. The spontaneous and IL-4-induced release of IgE was measured
      by ELISA. In patients with cypress pollen allergy, IL-4 and IgE release were
      significantly lower than in patients with other allergies. In the pollen
      sensitized group, IL-4 and IgE release were significantly higher during the
      pollen season than out of it. No variation in IL-4 or IgE release was observed in
      the polysensitized group. IFN-gamma production was not affected by the pollen
      season. These data show that the seasonal variations of IL-4 and IgE synthesis
      differ according to the sensitization of patients.

PMID- 8543753
TI  - Increased adhesion to vascular cell adhesion molecule-1 and intercellular
      adhesion molecule-1 of eosinophils from patients with asthma.
AB  - Adhesion of peripheral blood eosinophil and neutrophil granulocytes to the
      endothelial cell adherence receptors E-selectin, vascular cell adhesion molecule
      1, and intercellular adhesion molecule-1 has been measured. The study included
      patients with allergic rhinitis, patients with mild allergic and nonallergic
      asthma, and healthy individuals; 10 persons were in each group. In addition,
      assay of eosinophil and neutrophil cell surface expression of the receptor
      complex CD11b/CD18 was performed. Increased eosinophil adhesion to vascular cell
      adhesion molecule-1 (p < 0.05) and intercellular adhesion molecule-1 (p < 0.05)
      was demonstrated in the patients with a more labile asthma, that is, a peak
      expiratory flow rate variability of more than 10%, suggesting a relationship to
      the degree of ongoing inflammation in the airways of the patients. The increased
      eosinophil adhesion was most probably due to a functional upregulation of the
      CD11b/CD18 and very late activation antigen-4 receptors, because the number of
      receptors measured as cell surface expression was unaltered. The increased
      eosinophil adhesion in the patients with high peak expiratory flow rate
      variability appeared independent of atopy. The increased adhesion was not
      entirely specific to the eosinophils, because neutrophils from patients with a
      peak expiratory flow rate variability of more than 10% also demonstrated
      increased adhesion to intercellular adhesion molecule-1 (p < 0.05) when compared
      with neutrophils from the patients with low peak expiratory flow rate
      variability. In conclusion, the demonstrated priming of eosinophil adhesion to
      vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 might be
      one contributing mechanism behind the selective accumulation of eosinophils in
      the lung tissue of patients with asthma.

PMID- 8543754
TI  - IgE cross-reactivities against albumins in patients allergic to animals.
AB  - BACKGROUND: Type I allergic symptoms and severe asthma in particular are
      frequently caused by animal hair/dander proteins, among which albumins are
      possible cross-sensitizing allergenic components. METHODS: The significance and
      degree of IgE-cross-reactivities against various albumins were studied in a
      representative number (n = 200) of patients allergic to animals with hair/dander
      extracts, purified albumins from different animals, and a recombinant dog albumin
      fragment expressed in lysogenic Escherichia coli Y1089 and purified as a beta
      galactosidase fusion protein. RESULTS: Despite a high degree of sequence homology
      among different albumins, a remarkable variability of IgE cross-reactivities was
      observed, indicating that some patients were sensitized preferentially against
      certain albumins. Most of the patients allergic to albumins, however, reacted to
      dog, cat, and horse albumin, which also bound a high percentage of albumin
      specific IgE. CONCLUSION: The purified recombinant dog albumin fragment,
      representing 265 amino acids of the mature protein, bound IgE from all 15
      patients allergic to albumin tested suggesting its potential usefulness for
      diagnosis and perhaps therapy.

PMID- 8543755
TI  - Characterization of apple 18 and 31 kd allergens by microsequencing and
      evaluation of their content during storage and ripening.
AB  - Patients with tree pollinosis frequently report allergic reactions after
      ingestion of apples. The severity of apple allergy has been related to the
      variety of apples and their degree of maturity. To generate a serum pool that is
      representative of various IgE-binding patterns of apple-allergic sera, serum
      samples from 34 patients allergic to tree pollens were screened. Only 24 serum
      samples reacted to the apple extract. Pooled serum was used to identify allergens
      in apples. An efficient and consistent extraction method for apple fruits was
      used to compare the immunoreactivities of extracts of different varieties
      (McIntosh, Red Delicious, Granny Smith, and Golden Delicious) of freshly picked
      and store-purchased apples. We found that Golden Delicious apples had the
      greatest amount of the 18 kd allergen, which has been reported to be a potent IgE
      binding apple allergen. Store-purchased apples contained higher concentrations of
      the 18 kd allergen than freshly picked apples. In our study only 37.5% of sera
      reacted to the 18 kd protein, whereas 75% of the sera reacted to a 31 kd
      allergen. Other immunoreactive bands in apple extracts included proteins of 50,
      38, 16, 14, and 13 kd. The amino-terminal amino acid sequences of the two major
      allergens, 18 kd and 31 kd, were determined. These sequences shared approximately
      50% identity with disease resistance proteins of various plants or Bet v 1 in
      birch tree pollens. The appearance of various allergens was also investigated in
      mature apples during storage. The amount of 18 kd allergen increased
      significantly when apples were stored at 4 degrees C. However, under controlled
      atmospheric conditions in which oxygen- and carbon dioxide-induced ripening were
      regulated, the amount of 18 kd allergen remained unaffected. Because ripening and
      maturation were not associated with increases in 18 kd allergen content, the
      observed changes might be induced by factors related to disease resistance.

PMID- 8543756
TI  - Minimal persistent inflammation is present at mucosal level in patients with
      asymptomatic rhinitis and mite allergy.
AB  - The natural exposure to house dust mites causes sensitization in genetically
      susceptible patients. Persistent exposure of sensitized patients causes chronic
      inflammation, and consequently, hyperreactivity, thus promoting the development
      of clinical features. Recently, intercellular adhesion molecule-1 (ICAM-1)/CD54
      expression on epithelial cells triggered by allergen has been demonstrated and
      related to the inflammation caused by the allergic reaction. Therefore we
      evaluated the possible presence of inflammation (i.e., inflammatory cell
      infiltrate and ICAM-1/CD54 expression on epithelium) at conjunctival and nasal
      levels in patients with asymptomatic allergic rhinitis caused by mites, in their
      relatives living in the same environment, and in healthy volunteers. In addition,
      the possible relationship between inflammation and house dust mite allergen
      exposure was evaluated. Conjunctival and nasal scrapings of allergic subjects
      enrolled in the study showed many inflammatory cells. A mild ICAM-1/CD54
      expression on conjunctival and nasal epithelium was detectable in allergic
      subjects, whereas relatives and healthy volunteers showed few inflammatory cells
      and no ICAM-1/CD54 expression on epithelial cells. A detectable level of house
      dust mite, sufficient to cause sensitization, was found in all houses. This study
      demonstrates a minimal persistent inflammation at conjunctival and nasal levels
      constantly detectable in patients without symptoms who are sensitized to mites
      and continuously exposed to the natural allergens.

PMID- 8543757
TI  - Stimulation of dispersed nasal polyp cells by hyperosmolar solutions.
AB  - It has been suggested that hyperosmolarity may be one of the stimuli that provoke
      exercise-induced asthma and rhinitis. We investigated whether changes in
      osmolarity could result in increased levels of mediator release from nasal cells.
      Cells were dispersed from nasal polyps by enzymatic digestion and were incubated
      for 15 minutes with solutions of varying osmolarity obtained by the addition of
      mannitol to Hanks' balanced salt solution. After incubation was performed, cell
      supernatants were removed, and the release of 15-hydroxyeicosatetraenoic acid,
      prostaglandin2 leukotriene B4, and fibronectin was measured. Lactate
      dehydrogenase was measured to assess cell viability. Epithelial cells made up 40%
      to 60% of cells and mononuclear cells 40% to 65%. At 900 mOsm/kg H2O, which has
      been suggested as the osmolarity of the fluid lining the airways during exercise,
      we observed a significant increase (Wilcoxon W test) in the release of 15
      hydroxyeicosatetraenoic acid (p < 0.008), leukotriene B4 (p < 0.008), and
      prostaglandin2 (p < 0.008), but no significant increase in the release of
      fibronectin was seen. No significant increase was seen between lactate
      dehydrogenase and 15-hydroxyeicosatetraenoic acid release, suggesting that the
      increase in mediator levels was not caused by cell death. These results show that
      hyperosmolar solutions can induce activation of nasal cells, which may at least
      partly explain rhinitis caused by exercise.

PMID- 8543758
TI  - T-cell epitopes of Phl p 1, major pollen allergen of timothy grass (Phleum
      pratense): evidence for crossreacting and non-crossreacting T-cell epitopes
      within grass group I allergens.
AB  - BACKGROUND: The use of peptides representing T-cell epitopes of allergens is a
      modern concept for improvement of specific immunotherapy. A prerequisite for this
      approach is the identification of T-cell epitopes of atopic allergens. METHODS: T
      cell lines and 40 T-cell clones (TCC) specific for Phl p 1, the group I allergen
      of timothy grass (Phleum pratense), were established from the peripheral blood of
      nine patients allergic to grass pollen and mapped for epitope specificity by
      using overlapping dodecapeptides. Phenotype and cytokine production profile of
      TCC were investigated. Representative TCC were analyzed for HLA-restriction, T
      cell receptor V beta gene usage, and crossreactivity with grass pollen extracts
      from Dactylis glomerata, Poa pratensis, Lolium perenne, Secale cereale, and
      selected amino acid sequence-derived peptides. RESULTS: Patients displayed IgE
      binding to all grass species investigated. Forty TCC were established. Fifteen T
      cell epitopes could be identified on Phl p 1. Of 40 TCC, 39 displayed the helper
      cell (Th) phenotype; one clone was CD8+. Specific stimulation induced a Th2-like
      type of cytokine production in 20 of 39 TCC. Crossreactivity studies revealed
      crossreacting and non-crossreacting T-cell epitopes. CONCLUSION: Phl p 1, a major
      grass pollen allergen, harbors multiple T-cell epitopes. Species-specific and
      crossreacting T-cell epitopes exist among group I allergens of grasses. Epitope
      recognition patterns could not be correlated with particular HLA haplotypes. A
      restricted T-cell receptor V beta gene usage was not observed.

PMID- 8543759
TI  - Effect of topical doxepin cream on skin testing.

PMID- 8543760
TI  - Clothing--an important source of mite allergen exposure.

PMID- 8543761
TI  - New trends in immunopharmacology 1994. Tokyo, Japan, July 23, 1994. Proceedings.

PMID- 8543762
TI  - Lack of primary association between transporter associated with antigen
      processing genes and atopic dermatitis.
AB  - We examined polymorphisms of transporter associated with antigen processing (TAP)
      genes in 37 Japanese patients with atopic dermatitis and 52 control subjects. We
      have evaluated, again, the specificity polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method since our previous report and have
      also developed a mismatch PCR-RFLP method for discriminating two dimorphic sites
      of TAP1 gene and four dimorphic sites of TAP2 gene. Amplified products from
      genomic DNA were digested with restriction endonucleases: Sau3A1 for TAP1 codon
      333 (Ile-Val), AccI for TAP1 codon 637 (Asp-Gly), and BfaI for TAP2 codon 687
      (Stop-Gln). The other sites of TAP2 gene were analyzed by mismatch PCR-RFLP:
      AccII for TAP2 codon 379 (Val-Ile), RsaI for codon 565 (Ala-Thr), and MspI for
      codon 665 (Thr-Ala). We observed three TAP1 alleles and six TAP2 alleles.
      Infrequent allele TAP1 C was observed in one patient and one control subject. We
      did not identify any differences in TAP allele frequencies between those patients
      with atopic dermatitis and Japanese control subjects. Analysis of TAP gene
      polymorphisms will provide better understanding of susceptibility loci in HLA
      class II-associated disease because TAP genes are located between HLA-DQB1 and
      HLA-DPB1 loci.

PMID- 8543763
TI  - Analysis of disease-associated amino acid epitopes on HLA class II molecules in
      atopic dermatitis.
AB  - We investigated the association between HLA class II alleles and severe atopic
      dermatitis with high serum IgE levels (greater than 8000 U/ml). The frequencies
      of HLA-DRB1*1302 and DQB1*0604 were increased, whereas the frequency of HLA
      DQB1*0302 was decreased. A strong haplotype, HLA-DRB1*1302-DQB1*0604, has been
      reported in the Japanese population, and this haplotype is conserved in patients
      with AD. Further analysis of the amino acid epitopes on the HLA-DR beta 1 and DQ
      beta 1 domains revealed that DR beta 1 71Glu (RR = 5.71, p < 0.05) and DQ beta 1
      30His (RR = 3.25 p < 0.01), and 57Val (RR = 3.13, p < 0.05) were increased in
      frequency. DR beta 1 71Glu was exclusively unique to DRB1*1302. DQ beta 1 30His
      was shared by the following alleles: DQ beta 1*0501, *0502, *0503, and *0604,
      which were all increased in patients with AD. DQ beta 1 57Val was shared by
      DQB1*0501 and *0604. A well-known haplotype, HLA-DRB1*1302-DQB1*0604, contains DR
      beta 1 71Glu and DQ beta 1 30His and 57Val. Therefore HLA-DR beta 1 71Glu and/or
      DQ beta 1 30His/57Val are considered to play the most important role in the
      development of atopic dermatitis.

PMID- 8543764
TI  - Chronologic analysis of in situ cytokine expression in mite allergen-induced
      dermatitis in atopic subjects.
AB  - Patch testing with crude dust mite extracts, after removal of horny epidermal
      layers, was performed on normal-appearing skin of nine adult patients with atopic
      dermatitis who had high mite-specific IgE antibody levels. Positive skin
      reactions were observed in seven subjects. Skin biopsy specimens were obtained
      from positive reaction sites at 2, 6, 12, 24, and 48 hours after allergen
      challenge and subjected to histologic and immunohistochemical studies and
      extraction of RNA. Perivascular infiltration of small mononuclear cells began at
      2 hours, followed by eosinophilic infiltration at 6 hours, which peaked at 24 and
      48 hours. Increased expression of IL-4 messenger RNA was detected with reverse
      transcription polymerase chain reaction at 12 and 24 hours, whereas
      immunohistochemical staining with anti-IL-4 antibody showed positive reactions in
      connective tissue around infiltrating cells after 2 hours. Expression of IL-5 and
      tumor necrosis factor-alpha mRNA was upregulated 2 hours after an application of
      allergen. Interferon-gamma mRNA was not detected. These findings suggest the
      crucial role of TH2-type cytokines in initiating eosinophil infiltration of mite
      allergen-induced dermatitis in patients with atopic dermatitis.

PMID- 8543765
TI  - Detection of allergen-induced genes in peripheral blood mononuclear cells of
      patients with allergic asthma using subtractive hybridization.
AB  - When stimulated with mite antigens, peripheral blood mononuclear cells obtained
      from patients with mite allergy release eosinophil chemotactic factor, a type of
      protein. Complementary DNA libraries were formulated from both peripheral blood
      mononuclear cells stimulated with mite antigens and those not stimulated with
      mite antigens and underwent subtraction and differential screening. The authors
      obtained 13 genes for which expression had increased because of mite antigens. Of
      these, nine were mitochondrial genes; two, h-satellite DNA III; one, factor XIII;
      and one, ferritin heavy subunit. As a result of polymerase chain reaction on both
      cDNA libraries, IL-5 genes were amplified only from the cDNA library that had
      been stimulated with mite antigens.

PMID- 8543766
TI  - Differential expression of granulocyte-macrophage colony-stimulating factor and
      IL-3 receptor subunits on human CD34+ cells and leukemic cell lines.
AB  - Cytokines transduce their signals through specific receptors. Receptors for
      granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 share
      the common signal transducing subunit (beta c), whereas the alpha subunits
      function as specific ligand binding components. In this study we prepared
      specific mouse monoclonal antibodies against human GM-CSF receptor-alpha subunit
      (hGMR alpha) by immunizing mice with Ba/F3 cells transfected with hGMR alpha
      complementary DNA. Using these anti-hGMR alpha antibodies in combination with
      antibodies against IL-3 receptor-alpha (IL-3R alpha), beta c subunits, and c-kit,
      we examined expression patterns and modulation of these receptor subunits on
      several human hematopoietic cells, including CD34+ cells and leukemic cell lines.
      GMR alpha and IL-3R alpha were expressed on GM-CSF- and IL-3-responsive cell
      lines, such as TF-1 and UT-7, whereas the expression levels were much lower on UT
      7E, a GM-CSF- and IL-3-unresponsive subline of UT-7. The GMR alpha subunit was
      expressed only on mature granulocytes and monocytes, and IL-3R alpha was
      expressed on monocytes but not on mature granulocytes, and none of these subunits
      were expressed on lymphocytes. For CD34+ cells, GMR alpha was expressed more
      abundantly on CD34+ CD33high cells than on CD34+ CD33low cells, whereas IL-3R
      alpha was expressed more abundantly on CD34+ CD33low cells than on CD34+ CD33high
      and CD34+ CD33neg cells. Slight but significant expression of the beta c subunit
      was detected on CD34+ cells. Expression of not only GMR alpha and IL-3R alpha
      subunits but also c-kit was specifically downregulated by 48-hour incubation with
      their respective ligands. Receptor transmodulation between GM-CSF, IL-3, and stem
      cell factor (or kit ligand) was not detected on CD34+ cells in 48-hour cultures.
      We also detected upregulation of these alpha subunits by IL-1 alpha and
      interferon-gamma on leukemic cell lines. Our study showed expression levels for
      each receptor subunit--including GMR, IL-3R, and c-kit on human bone marrow and
      peripheral blood cells and leukemic cell lines--and revealed differential
      regulation of the expression of the receptor subunits.

PMID- 8543768
TI  - Gene structures of the alpha subunits of human IL-3 and granulocyte-macrophage
      colony-stimulating factor receptors: comparison with the cytokine receptor
      superfamily.
AB  - Recently, many genes encoding the members of the cytokine receptor superfamily
      (CRSF), which have common structural features, have been characterized. Analyses
      on the structures of the genes encoding the alpha subunits of human IL-3 (hIL-3R
      alpha) and granulocyte-macrophage colony-stimulating factor receptors (hGMR
      alpha) revealed that they have the structural features common to all members of
      the CRSF (i.e., conservation of the intron phase pattern as "1-2-1-0-1" rule in
      the fibronectin type III domains located in extracellular segments of type I
      cytokine receptor subunits. This finding led us to propose a possible model for
      gene evolution for the CRSF. We pointed out that the CRSF genes derived from a
      putative common ancestral gene. In addition to these common features, we found an
      additional intron that is unique to the IL-3R alpha and the GMR alpha genes. This
      additional intron suggests that the IL-3R alpha and the GMR alpha genes evolved
      closely in the evolution process of the CRSF genes. This evidence and results of
      recent studies on the evolution of mammalian X chromosome make it tempting to
      speculate that a putative common ancestral gene of the subfamily including IL-3R
      alpha, GMR alpha, and IL-5R alpha emerged in an autosome at least before the
      divergence of marsupials and eutherian mammals, early in the 200 million-year
      history of mammals.

PMID- 8543767
TI  - Roles of the cytoplasmic domains of the alpha and beta subunits of human
      granulocyte-macrophage colony-stimulating factor receptor.
AB  - The high-affinity and functional granulocyte-macrophage colony-stimulating factor
      receptor (GMR) is composed of two distinct subunits, alpha and beta; and the
      cytoplasmic domain of the beta subunit is essential to transduce growth-promoting
      signals. In contrast to the beta subunit, the role of the alpha subunit is not
      well characterized. We examined the requirement of the cytoplasmic domain of the
      alpha subunit and its functional region by deletion analyses. We demonstrated
      that the cytoplasmic domain of the alpha subunit, especially 29 amino acids
      residues near the transmembrane domain, was absolutely required for various
      signaling events including activation of immediate early genes, induction of
      tyrosine phosphorylation of cellular proteins, and cell growth. We further
      analyzed the role of the cytoplasmic domain of each subunit by constructing
      chimeric subunits, designated alpha/beta and beta/alpha, by exchanging
      cytoplasmic domains of the alpha and beta subunits of human (h) GMR.
      Reconstituted high-affinity chimeric hGMRs, hGMR(alpha/beta,beta/alpha) and
      hGMR(alpha/beta,beta), transduced signals at levels similar to the wild type
      hGMR(alpha,beta) in Ba/F3 cells and in NIH3T3 cells. These observations indicate
      that the original configuration between the extracellular and the cytoplasmic
      domains of the hGMR(alpha,beta) subunits is not required and that
      hGMR(alpha/beta,beta) transduced signals through the cytoplasmic domain of the
      beta subunit in an oligomeric form, without involvement of the cytoplasmic domain
      of the alpha subunit. Therefore human granulocyte-macrophage colony-stimulating
      factor signals are mainly transduced through the beta subunit, and the
      cytoplasmic domain of the alpha subunit is likely to activate the beta subunit in
      the normal hGMR.

PMID- 8543769
TI  - Regulation of expression of the IL-2 and IL-5 genes and the role of proteins
      related to nuclear factor of activated T cells.
AB  - Cyclic adenosine monophosphate (cAMP) inhibits phorbol 12-myristate 13-acetate
      (PMA)-induced IL-2 production while it inhibits IL-5 production at the
      transcriptional level in EL-4, a mouse lymphoma line. The -321 to +46 region of
      the mouse IL-2 promoter is required for activation by PMA and inhibition by cAMP.
      This promoter region contains several elements that interact with transcription
      factors, such as nuclear factor of activated T cells (NF-AT), NF-kappa B, AP-1,
      and octamer. With use of reporter plasmid carrying multiple copies of each
      element, we found that the construct that contained the NF-AT site was most
      effective for responding to PMA activation and cAMP inhibition. In
      electrophoretic mobility shift assay (EMSA), PMA-induced NF-AT binding complex
      was altered by cAMP. Furthermore, overexpression of the cytoplasmic component of
      NF-AT abrogated the inhibitory action of cAMP. These results indicate that the NF
      AT site is a target of the inhibitory action of cAMP. We have previously reported
      that the -1200 to +33 region of the mouse IL-5 promoter can mediate
      transcriptional stimulation by PMA and cAMP in EL-4 cells. Here we identified the
      element IL-5P, which is required for maximal activation of the IL-5 promoter. We
      found that this element is homologous to the binding site for NF-AT and
      interacted with NF-AT-related factors induced by PMA and cAMP. Thus it appears
      that an NF-AT factor is involved in the regulation of IL-5 gene transcription.

PMID- 8543770
TI  - Role of LFA-1/ICAM-1-dependent cell adhesion in CD40-mediated inhibition of anti
      IgM antibody-induced B-cell death.
AB  - Cross-linking of surface IgM by anti-IgM antibody caused activation-induced cell
      death of a surface IgM+, IgD+ human B lymphoma cell line, B104. The dying B104
      cells did not show the morphology of apoptosis but did show that of necrosis.
      However, anti-IgM antibody caused apoptosis of another surface IgM+, IgD+ human B
      lymphoma cell line, DND-39. The influx of extracellular Ca2+ was necessary for
      the cell deaths of B104 and DND-39 caused by anti-IgM antibody. Their cell deaths
      were inhibited by cyclosporine. The anti-IgM antibody-induced cell death of DND
      39, but not that of B104, was prevented by costimulation with anti-CD40 antibody.
      In human peripheral blood B-cells, anti-IgM antibody inhibited cell cycle
      transition induced by Staphylococcus aureus Cowan I at the G2/M interphase
      without inhibition of DNA synthesis. In this system, too, anti-CD40 antibody
      canceled the inhibitory signal transduced through surface IgM and increased the
      number of M phase cells. Blocking antibodies against the leukocyte function
      associated antigen-I/intercellular adhesion molecule-1 system decreased the
      rescue effect of anti-CD40 antibody in both DND-39 cells and peripheral B-cells,
      which shows that leukocyte function-associated antigen-1/intercellular adhesion
      molecule-1-dependent cell adhesion plays an important role in the CD40-mediated
      inhibition of surface IgM-mediated negative signals.

PMID- 8543771
TI  - Functional significance of IL-4 receptor on B cells in IL-4-induced human IgE
      production.
AB  - IL-4 with the IgE-inducing activity is shown to upregulate the expression of IL-4
      receptor (IL-4R) on lymphocytes. Antisense strategy was used that aimed at
      investigating the significance of IL-4-induced upregulation of IL-4R on B cells
      in human IgE production. When an antisense phosphorothioate oligodeoxynucleotide
      to IL-4R (S-oligo 1) was added to B cells together with IL-4, the agent
      selectively abrogated the upregulation of IL-4R without affecting its
      constitutive level expression. Moreover, S-oligo 1 had a suppressive effect on
      the T-cell-independent synthesis of IgE by B cells costimulated with IL-4 and
      anti-CD40 antibody. This suppression was accompanied by inhibition of mature but
      not germline C epsilon transcription. These findings indicate that constitutively
      expressed IL-4R provides a signal or signals responsible for the induction of
      germline C epsilon transcription and suggest that IL-4R upregulation may be
      required for the subsequent class switch recombination that leads to mature C
      epsilon transcription and IgE synthesis. The IL-4R signal transduction mechanism
      underlying germline C epsilon transcription was also analyzed in a human Burkitt
      lymphoma B-cell line, DND39. Induction of germline C epsilon transcripts in DND39
      cells by IL-4 required at least two distinct signaling cascades. One was mediated
      by enhancement of tyrosine phosphorylation of a 57 kd protein associated with
      phospholipase C-gamma 1 (PLC-gamma 1) that resulted in PLC-gamma 1 activation,
      inositol lipid hydrolysis, and protein kinase C delta translocation. The other
      was dependent on phosphatidylinositol 3-kinase, whose activation induced protein
      kinase C zeta translocation. In fact, kinase inhibitors such as herbimycin A, K
      252a, and wortmannin were effective in inhibiting IL-4-induced germline C epsilon
      transcription. Therefore, in addition to activation of protein tyrosine kinases,
      coordinated actions of PLC-gamma 1 and phosphatidylinositol 3-kinase may be
      involved in IL-4-driven germline C epsilon transcription in DND39 cells.

PMID- 8543772
TI  - Physical association of Fc receptor gamma chain homodimer with IgA receptor.
AB  - The receptor for IgA, Fc alpha R, consists of one IgA-binding alpha chain and a
      signal-transducing dimeric FcR gamma chain. Immunoprecipitation with an anti-Fc
      alpha R alpha chain monoclonal antibody from the lysates of U937 cells (human
      monocytic cell line) revealed an association of 20 kd (unreduced) and 10 kd
      (reduced) molecules to Fc alpha R alpha chain on sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). These molecules were confirmed to
      be FcR gamma chain by immunoblotting probed with anti-FcR gamma chain antibody. A
      serial immunoprecipitation with both antibodies further ascertained the FcR gamma
      association with Fc alpha R alpha. The lysates precleared with anti-FcR gamma
      antibody were subjected to the second immunoprecipitation with an anti-Fc alpha R
      alpha monoclonal antibody. By this preclearance, FcR gamma disappeared, and the
      Fc alpha R alpha appeared to be significantly decreased on SDS-PAGE, suggesting
      that a part of Fc alpha R alpha was co-absorbed with FcR gamma. Therefore, it may
      be likely that Fc alpha R is expressed in two forms, namely, with or without FcR
      gamma. We next reconstituted the Fc alpha R alpha-FcR gamma association by
      introducing both chains into host cells. The expression of Fc alpha R alpha was
      achieved by introducing Fc alpha R alpha alone, and the cointroduction of FcR
      gamma did not enhance Fc alpha R alpha expression on the cell surface, suggesting
      again the occurrence of the two forms of FC alpha R.

PMID- 8543773
TI  - IL-4 upregulates Fc epsilon RI alpha-chain messenger RNA in eosinophils.
AB  - By using the reverse transcription polymerase chain reaction and Southern blot
      hybridization, we demonstrated that Fc epsilon RI alpha-chain (Fc epsilon RI
      alpha) messenger RNA was expressed in eosinophils purified from the peripheral
      blood of patients with allergic rhinitis and that this expression was enhanced by
      IL-4. However, studies in which flow cytometry or immunostaining was used did not
      reveal the expression of Fc epsilon RI alpha protein on eosinophils from
      peripheral blood. Neither IL-4 alone nor the combination of IL-4 and other
      cytokines could induce detectable Fc epsilon RI alpha protein; nevertheless, they
      do express Fc epsilon RI alpha mRNA. Double-labeling immunostaining on cryostat
      sections of nasal mucosa clearly demonstrated that some Fc epsilon RI alpha
      positive cells were eosinophil cationic protein-positive, which confirms their
      eosinophilic nature. Not all the eosinophil cationic protein-positive cells
      express on Fc epsilon RI alpha signal. Considering that Fc epsilon RI alpha mRNA
      was detectable in four of five samples of eosinophils from those patients with
      nasal allergy and that only one of five eosinophil samples from normal subjects
      expressed Fc epsilon RI alpha mRNA, the level of Fc epsilon RI expression may be
      correlated with the activation of eosinophils. It seems very likely that some
      other unidentified factors are required for the process from the expression of Fc
      epsilon RI alpha mRNA to that of Fc epsilon RI as a protein.

PMID- 8543774
TI  - The role of calcineurin in immune system responses.

PMID- 8543775
TI  - Modulation of Langerhans cell function by epidermal nerves.
AB  - Many if not most epidermal Langerhans cells appeared to be closely associated
      anatomically with calcitonin gene-related peptide (CGRP)-containing nerves as
      determined by confocal laser scanning microscopy. Furthermore, a small proportion
      of Langerhans cells had immunoreactive CGRP at or near their cell surfaces,
      suggesting that nerves are capable of depositing CGRP at or near Langerhans
      cells. CGRP inhibited Langerhans cell antigen-presenting capability for
      elicitation of delayed-type hypersensitivity in immunized mice to present
      alloantigens in the mixed epidermal cell-lymphocyte reaction and to present a
      protein antigen to a responsive hybridoma. As a whole, these data suggest the
      possibility that products of nerves within the epidermis might serve to regulate
      Langerhans cell function. The apparent apposition of epidermal nerves with
      Langerhans cells suggests a possible locus of interaction between the nervous
      system and the immune system within the skin.

PMID- 8543776
TI  - Differential subcellular localization of neural isoforms of the catalytic subunit
      of calmodulin-dependent protein phosphatase (calcineurin) in central nervous
      system neurons: immunohistochemistry on formalin-fixed paraffin sections
      employing antigen retrieval by microwave irradiation.
AB  - We examined the immunohistochemical distribution of the two mammalian isoforms of
      calcineurin catalyic subunits, A alpha and A beta, in central nervous system
      (CNS) tissues of cows, rats, and humans. Cryostat sections and paraffin sections
      of parformaldehyde-fixed tissues were stained with antipeptide antibodies for
      each isoform. The same localization pattern was observed in both cryostat and
      paraffin sections. In the latter, the intensity of the staining was dramatically
      enhanced by microwave irradiation. Calcineurin isoforms were localized in a
      variety of nerve cells but not in neuroglial cells. Their differential expression
      as the A alpha isoform in the nucleus and the A beta isoform in the cytoplasm was
      present in a variety of CNS nerve cells, most distinctively in Purkinje cells of
      the cerebellum and pyramidal cells of the cerebrum, irrespective of species.
      These results suggest that each isform has distinct intracellular sites of action
      in CNS neurons and that the phenomenon has been conserved during mammalian
      evolution.

PMID- 8543777
TI  - Tyrosine phosphorylation in desmosomes and hemidesmosomes of the corneal
      epithelium.
AB  - We examined the localization of phosphotyrosine (p-Tyr)-modified proteins in the
      normal corneal epithelium using affinity-purified rabbit anti-p-Tyr antibody.
      Normal rat cornea was fixed and semi-thin and ultra-thin frozen sections were
      prepared. Immunofluorescence microscopy showed that p-Tyr was distributed along
      the cell membrane of the corneal epithelium. Immunogold electron microscopy
      revealed that the labeling is exclusively localized in the desmosomes and
      hemidesmosomes. A fraction enriched with desmosomes was extracted from the bovine
      corneal epithelium and examined by Western blotting. Immunoblotting for p-Tyr
      showed eight prominent bands (290, 200, 190, 115, 85, 62, 50, and 47 kD) in the
      desmosomal fraction. The enrichment of p-Tyr in desmosomes and hemidesmosomes of
      the corneal epithelium suggests that these cell-to-cell and cell-to-substrate
      junctions are involved in signal transduction.

PMID- 8543778
TI  - Improved resolution of fibronectin mRNA expression in the inner ear using laser
      scanning confocal microscopy.
AB  - We describe a modified in situ hybridization protocol for localizing and
      quantifying fibronectin gene expression at the cellular level in paraffin
      sections of rat temporal bone. When combined with a novel analytical approach
      using laser scanning confocal microscopy (LSCM), this protocol significantly
      improved the resolution, sensitivity, and specificity of existing procedures for
      evaluating fibronectin synthesis in developing inner ear. For simultaneous
      viewing of cochlear anatomy and the autoradiographic signal, transmitted light
      images of the cochlea were collected separately from LSCM reflected light images
      of the autoradiographic silver grains and then the two images were electronically
      merged. Within the first 2 microns below the surface of the emulsion, silver
      grains were clustered specifically over hybridized cells. In contrast,
      nonspecific silver grain development (i.e., background noise) was confined
      primarily to the lower 5 microns of the emulsion adjacent to the tissue section.
      Limiting the volume of the emulsion examined in the LSCM analysis, i.e.,
      restricting the range of optical sectioning to the first 2 micron below the
      surface of the emulsion, effectively minimized nonspecific background noise and
      maximized the specificity of the hybridization signal. The improvements offered
      by the described methodological approaches are equally appropriate for non
      calcified tissues.

PMID- 8543779
TI  - Distribution of peptidyl-glycine alpha-amidating mono-oxygenase (PAM) enzymes in
      normal human lung and in lung epithelial tumors.
AB  - C-terminal alpha-amidation is a post-translational modification necessary for the
      biological activity of many regulatory peptides produced in the respiratory
      tract. This modification is a two-step process catalyzed by two separate enzyme
      activities, both derived from the peptidyl-glycine alpha-amidating mono-oxygenase
      (PAM) precursor. The distribution of these two enzymes, peptidyl-glycine alpha
      hydroxylating monoxygenase (PHM) and peptidyl-alpha-hydroxyglycine a amidating
      lyase (PAL), was studied in the normal lung and in lung tumors using
      immunocytochemical methods and in situ hybridization. In normal lung the enzymes
      were located in some cells of the airway epithelium and glands, the endothelium
      of blood vessels, some chondrocytes of the bronchial cartilage, the alveolar
      macrophages, smooth muscle cells, neurons of the intrinsic ganglia, and in
      myelinated nerves. A total of 24 lung tumors of seven different histological
      types were studied. All cases contained PAM-immunoreactive cells with various
      patterns of distribution. All immunoreactive cells were positive for the PHM
      antiserum but only some of them for the PAL antiserum. The distribution of PAM co
      localizes with some other previously described amidated peptides, suggesting that
      amidation is an important physiological process taking place in the normal and
      malignant human lung tissue.

PMID- 8543780
TI  - CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is
      expressed in epithelium, endothelium, and myeloid cells in a wide range of normal
      human tissues.
AB  - CD66a, also called biliary glycoprotein (BGP), is a member of the
      carcinoembryonic antigen (CEA) family and of the immunoglobulin superfamily.
      CD66a is the human homologue of Cell-CAM, a well-defined cell adhesion molecule
      of the rat. In the present study a monoclonal antibody specific for CD66a was
      used to locate CD66a in human tissues. CD66a is expressed in epithelia, in
      certain endothelia, and in cells of the myeloid lineage. Hepatocytes were stained
      along the bile canaliculi. A characteristic apical membranous staining was
      observed in enterocytes, superficial absorptive cells of the colon, in the
      epithelia of esophageal and Brunner's glands, bile ducts and gallbladder,
      pancreatic ducts, proximal tubules of the kidney, prostate, endometrium, and
      mammary ducts. Selective staining of endothelia was present in glomeruli and vasa
      recta of the kidney, small placental vessels, adrenal sinusoids, endometrium, the
      prostate. Among the cells of the myeloid lineage, granulocytes and myelocytes
      were positive. The expression of CD66a by human cells and tissues is well
      comparable with the expression reported for Cell-CAM, the rat counterpart of
      CD66a. The wide tissue distribution of CD66a indicates that CD66a is a prominent
      human adhesion molecule.

PMID- 8543781
TI  - Quantitative and morphological aspects of Unicryl versus Lowicryl K4M embedding
      in immunoelectron microscopic studies.
AB  - In this study we compared the recently commercialized electron microscopy
      embedding resin Unicryl with the well-known resin Lowicryl K4M with regard to
      morphological and immunohistochemical preservation properties. The standard
      embedding procedure recommended by the manufacturer for the use of Unicryl
      resulted in considerable morphological alterations of the tissue, with the
      appearance of large gaps in and between the cells of the examined tissue.
      Morphometric analysis pointed to a swelling of the extracellular matrix as the
      main cause of these morphological artifacts. A slight modification in the
      protocol to correct this artifact is proposed and tested. Immunohistochemically,
      tissue embedded in Unicryl resulted in a significantly stronger immunogold
      labeling than identical tissue embedded in Lowicryl K4M. From the results of this
      technical study, it can be concluded that Unicryl embedding is a valuable new
      tool to supplement the available techniques for immunoelectron microscopic
      studies.

PMID- 8543782
TI  - Differential expression of gap junction proteins connexin32 and 43 in rat
      submandibular and sublingual glands.
AB  - We examined the expression and localization of the gap junction proteins
      connexin32 and 43 in rat submandibular and sublingual glands. Western blot
      analysis with anti-connexin32 and 43 antibodies showed bands of approximately 27
      KD and 43 KD, respectively, in both glands. Immunofluorescence microscopy
      demonstrated the presence of reactive spots for connexin32 between acinar cells
      in both glands. The frequency of connexin32-positive spots in the submandibular
      glands was approximately equal to that in the sublingual glands. In contrast,
      reactive spots for connexin43 were observed at the periphery of the alveolar
      structures in both glands. The connexin43-positive spots in the sublingual glands
      were more frequent and larger than those in the submandibular glands. No positive
      spots for both connexins were detected between duct cells in either gland.
      Immunoelectron microscopy revealed that connexin32 was localized to the gap
      junctional membranes between acinar cells. Immunolabeling for connexin43 was
      located on the gap junctions between thin processes of myoepithelial cells. These
      results suggest that connexin32 of the gap junction is associated with regulation
      of the secretory function of acinar cells and that connexin43 is associated with
      that of contraction of the myoepithelial cells in rat salivary glands.

PMID- 8543783
TI  - Expression of sulfated gp300 and changes in glycosylation during pancreatic
      development.
AB  - The pancreatic zymogen granule membrane protein gp300 is the major sulfated
      glycoprotein of the mouse acinar cell and has been proposed to be an important
      structural component of the zymogen granule membrane. A prediction of this
      proposed function is that gp300 expression should be coordinately regulated with
      the digestive enzymes and appearance of zymogen granules during differentiation
      of acinar cells in fetal development. By Western blots and immunolocalization
      with a polyclonal antiserum to gp300, we found that gp300 protein expression
      paralleled expression of amylase and the appearance of zymogen granules in
      differentiating acinar cells. Lectin blots were performed to assess the
      glycoconjugate composition of gp300 during development. Using the fucose binding
      lectin Ulex europaeus I, we found that gp300 acquires this carbohydrate only
      postnatally, temporally correlated with weaning. In addition, gp300 showed
      complex changes during postnatal development in reactivity with the galactose
      binding lectin peanut agglutinin (PNA) and the sialic acid binding lectin Maackia
      amuresis (MAA). Levels of reactivity of PNA and MAA were reciprocal, suggesting
      that sialylation of galactose (which can block peanut agglutinin binding) was not
      constant on gp300 during development.

PMID- 8543784
TI  - Ultrastructural immunogold localization of interleukin 5 to the crystalloid core
      compartment of eosinophil secondary granules in patients with atopic asthma.
AB  - Bronchial biopsies from two patients with atopic asthma were analyzed by
      immunogold labeling to detect the ultrastructural location of interleukin 5 (IL
      5). In eosinophils, IL-5 was localized to the electron-dense crystalloid core
      compartment of the secondary or specific eosinophil granules. Other structures in
      the eosinophils were unlabeled. No IL-5 was detected in mast cells. Control
      sections incubated with an irrelevant primary antibody were negative. This study
      demonstrates that pre-formed IL-5 is stored within the major population of
      secondary granules in human eosinophils.

PMID- 8543785
TI  - A differentiated silver intensification procedure for the peroxidase
      diaminobenzidine reaction.
AB  - Several silver-based procedures have been developed to intensify the peroxidase
      catalyzed diaminobenzidine polymer used as a marker in immunohistochemistry. Many
      of these methods use acutely unstable reagents or reagents that are not amenable
      to batch processing. We describe a new procedure with an initial treatment in
      dilute ammoniacal silver, followed by a differentiation step to remove background
      staining and a final toning in 0.2% gold chloride. The procedure provides a jet
      black intensification of the tan diaminobenzidine product, is amenable to batch
      processing of free-floating sections and slide-mounted sections, and does not
      require acid-cleaned glassware.

PMID- 8543786
TI  - Rapid screening and detection of cellular cross-contamination in cell cultures: a
      new application of cytochemistry.

PMID- 8543787
TI  - Cystatin mRNA is expressed by the ciliary epithelium of the chick eye.

PMID- 8543788
TI  - The immunologic properties of DNA.

PMID- 8543789
TI  - Polymorphic nucleotides within the human IL-4 promoter that mediate
      overexpression of the gene.
AB  - Atopy, which predisposes individuals to develop asthma, severe systemic
      anaphylaxis, and atopic dermatitis, is usually associated with dramatically
      elevated total serum IgE levels and is thought to be controlled by a major
      susceptibility gene and multiple minor susceptibility genes. A recent sib-pair
      analysis revealed a tight linkage between markers on 5q31.1 and a major
      susceptibility gene controlling total serum IgE levels. Due to its location
      within this cluster and its biologic role in Ig class switching and Th2 cell
      differentiation, the IL-4 gene has emerged as one major candidate for the atopy
      gene. In one model, polymorphisms within IL-4 regulatory elements might result in
      overexpression of the gene, amplifying Th2 cell differentiation and class
      switching to IgE. In support of this model, we report that the human IL-4
      promoter exists in multiple allelic forms that exhibit distinct transcriptional
      activities in IL-4-positive T cells. A particular allele has an unusually high
      transcriptional activity. A nucleotide substitution within a recently described
      OAP40 element located just upstream of an NF-AT site (P sequence) appears to be
      largely responsible for the increased promotor strength of this particular
      allelic form of the IL-4 promoter. In EMSAs, this substitution results in a
      markedly enhanced affinity for sequence-specific complexes exhibiting an AP-1
      specificity. The identification of allelic nucleotides, which results in
      overexpression of the IL-4 gene, provides specific targets for a comprehensive
      screening of atopic and nonatopic individuals and may provide a clue for genetic
      predisposition for atopy.

PMID- 8543790
TI  - LPS induces CD14 association with complement receptor type 3, which is reversed
      by neutrophil adhesion.
AB  - CD14, a glycosylphosphatidyl inositol (GPI)-linked membrane protein, is a key
      membrane binding site for LPS (endotoxin). Although CD14 lacks transmembrane and
      cytoplasmic sequences, it activates CR3-mediated leukocyte adhesion and cytokine
      release. Since CR3 has been shown to interact with other GPI-linked membrane
      proteins, we tested the hypothesis that CD14 can physically associate with CR3.
      Using qualitative and quantitative resonance energy transfer microscopy, we show
      that LPS in the presence of serum or LPS binding protein triggers formation of
      CD14-CR3 complexes. Kinetic studies show that CD14-CR3 complexes dissociate as
      neutrophils attach to substrates. We speculate that LPS-charged CD14 enhances CR3
      mediated adhesion by directly binding to CR3.

PMID- 8543791
TI  - An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4
      stimulated T cell proliferation.
AB  - Alternative splicing of mRNA can generate protein isoforms that are
      preferentially expressed in different tissues or during different states of cell
      differentiation or activation. Protein isoforms may have different functions. In
      this study, we cloned, expressed, and tested functional effects of a naturally
      occurring splice variant of human IL-4, called IL-4 delta 2. In IL-4 delta 2, the
      second exon of IL-4 is omitted by alternative splicing, with exons 1, 3, and 4
      joined in an open reading frame. We found that IL-4 delta 2 RNA is expressed in
      the PBMC of all donors tested, usually in lower amounts than IL-4 RNA. In
      contrast, IL-4 delta 2 RNA is expressed in much higher levels than IL-4 RNA in
      thymocytes and bronchoalveolar lavage cells, suggesting tissue specificity of
      expression. IL-4 delta 2 cDNA was expressed in yeast. Recombinant human (rh) IL-4
      delta 2 was partially purified and found to be glycosylated, with a protein core
      of 13 to 15 kDa. Unlike rhIL-4, rhIL-4 delta 2 did not act as a costimulator for
      T cell proliferation. However, rhIL-4 delta 2 inhibited the ability of rhIL-4 to
      act as a T cell costimulator. Inhibition was independent of glycosylation and was
      not mediated by toxicity. Iodinated IL-4 delta 2 was found to bind specifically
      to human PBMC and tumor lines known to express IL-4 receptors. Excess unlabeled
      IL-4 inhibited cellular binding of labeled IL-4 delta 2. Thus, rhIL-4 delta 2 is
      a naturally occurring splice variant of IL-4 that is preferentially expressed in
      the thymus and airways and inhibits function of complete IL-4. The balance
      between IL-4 and IL-4 delta 2 may be important in the regulation of IL-4 effects.

PMID- 8543793
TI  - The class II MHC I-Ag7 molecules from non-obese diabetic mice are poor peptide
      binders.
AB  - The class II molecules of the diabetes-prone NOD mice, I-Ag7, showed very limited
      amounts of stable form when analyzed by SDS-PAGE. We included the analysis of
      spleen B cells and B lymphoma cells transfected with I-Ag7 genes. Early during
      bio-synthesis there was invariant chain binding to the alpha beta-chains.
      Examination of APCs from F1 mice (NOD x C57BL/6) indicated that the same APC
      expressed high levels of unstable I-Ag7 and normal amounts of stable class II
      molecules compared with the other haplotype (I-Ab). The half-life of I-Ag7
      peptide complexes on the cell surface of APC was significantly shorter than that
      of other class II haplotypes. Direct biochemical demonstration of peptide
      interactions with I-Ag7 was difficult to demonstrate. In T cell assays, the
      immunogenic peptides, including the diabetogenic Ag, were rapidly lost when
      peptide-pulsed APCs were washed free of peptide. We hypothesize that the weak and
      unstable peptide-binding property of I-Ag7 molecules does not favor the
      elimination or inactivation of autoreactive T cells.

PMID- 8543792
TI  - Structure and expression of murine CD30 and its role in cytokine production.
AB  - Murine CD30 cDNA predicts a protein of 498 amino acids with homology to the TNF
      receptor family of proteins characterized by repeated cysteine-rich motifs in the
      extracellular domain. Murine CD30, although homologous to human CD30, has a 90
      amino acid gap in an extracellular region that appears to be duplicated in human
      CD30. Murine CD30 cDNA was shown to be functional through the production of a
      soluble murine Ig fusion protein (CD30-Ig) that was active in binding to cells
      that expressed CD30 ligand. CD30-Ig also served as an immunogen for the
      production of hamster anti-mouse CD30 mAbs, which recognized both CD30 expressed
      by murine lymphocytes and CD30 expressed by cells transfected with murine CD30
      cDNA. CD30 mRNA is highly expressed in the thymus and in activated spleen cells,
      but not in other tissues tested. In anti-CD3-activated spleen cells, CD30 ligand
      is expressed primarily by CD4+ T cells, with peak expression at days 1 and 2,
      whereas CD30 is expressed primarily by CD8+ T cells, with peak expression on days
      4 and 5. Stimulation of CD30 by plate-bound anti-CD30 directly signaled for IL-5
      but not IFN-gamma production by CD30+ CTL lines. These studies demonstrate that
      CD30 directs cytokine secretion and suggest that CD30 signaling may be pivotal in
      the pattern of cytokine production by T cells.

PMID- 8543794
TI  - Fas- and activation-induced apoptosis are reduced in human T cells preactivated
      in the presence of TGF-beta 1.
AB  - The elimination of activated but not resting T cells involves apoptosis induced
      either by restimulation via the TCR/CD3 complex, CD2, or by signaling through the
      Fas Ag. The factors regulating the shift of an apoptosis-resistant to an
      apoptosis-sensitive phenotype and vice versa have not so far been clarified. Here
      we report that TGF-beta 1, when present during a PHA activation course,
      significantly increases viability of human T cells upon reculture in medium
      alone, following restimulation via CD2, CD3, or after triggering the Fas Ag.
      Using DNA gel electrophoresis and an in situ nick translation technique we
      further show that activation-induced and Fas-mediated apoptosis are reduced in T
      cells that were prestimulated with PHA plus TGF-beta 1, compared with control
      cells prestimulated with PHA alone. Moreover, when PHA-preactivated T cells are
      further expanded in IL-2, inclusion of TGF-beta 1 results in higher cell yields
      at any timepoint from day 30 to 75 of cell culture compared with control cultures
      without TGF-beta 1. However, no differences in Fas or bcl-2 protein expression
      are found between cells stimulated in the absence or presence of TGF-beta 1.
      Together, our data identify TGF-beta 1, when present during an activation course,
      as an important viability factor possibly of importance for the generation of
      effector and/or long-lived memory T cells.

PMID- 8543795
TI  - B7-1 but not B7-2 efficiently costimulates CD8+ T lymphocytes in the P815 tumor
      system in vitro.
AB  - We recently have developed a method to generate primary P815-specific CTL in
      vitro from normal syngeneic splenocytes by employing transfection of B7-1
      combined with exogenous IL-12 and IL-6. Surprisingly, when the homologous
      costimulator molecule B7-2 was substituted for B7-1 in this system, no specific
      CTL activity was obtained. Similarly, B7-1- but not B7-2-transfected P815 cells
      generated alloantigen-specific CTL activity from C57BL/6, accessory cell- and
      CD4(+)-depleted splenocytes, and costimulated proliferation of CD8+ lymphocytes
      in the presence of low doses of anti-CD3 mAb. In all systems, combined expression
      of both B7-1 and B7-2 costimulated as effectively as B7-1 alone, arguing against
      delivery of a dominant negative signal by B7-2. Proliferation of allogeneic,
      CD4(+)-depleted splenocytes in response to P815 cells, which relies on
      costimulation by normal accessory cells, was inhibited by anti-B7-1 but not anti
      B7-2 mAbs. Finally, indirect evidence suggested a higher avidity of B7-1+ cells
      than B7-2+ cells for CTLA4. Thus, at least in the context of primary stimulation
      by irradiated P815 transfectants, B7-1 appears to be superior to B7-2 at
      costimulation of CD8+ T lymphocytes.

PMID- 8543797
TI  - Reduction of early B lymphocyte precursors in transgenic mice overexpressing the
      murine heat-stable antigen.
AB  - To study the role of the murine heat-stable Ag (HSA) in lymphocyte maturation, we
      generated transgenic mice in which the HSA cDNA was under the transcriptional
      control of the TCR V beta promoter and Ig mu enhancer. The HSA transgene was
      expressed during all stages of B lymphocyte maturation. Expression was first
      detected in the earliest lymphoid-committed progenitors, which normally do not
      express HSA, and subsequently reached the highest levels in pro- and pre-B cells.
      In bone marrow, the number of IL-7-responsive clonogenic progenitors was < 4% of
      normal, whereas the frequency of earlier B lymphocyte-restricted precursors,
      detectable as Whitlock-Witte culture-initiating cells, was normal. Pro- and pre-B
      cells detected by flow cytometry were reduced by approximately 50% relative to
      controls. Mature splenic B cells were also reduced but to a lesser extent than in
      marrow, and their response to LPS stimulation was impaired. Reconstitution of
      SCID and BALB/c-nu/nu mice with HSA transgenic marrow indicated that the
      perturbations in B lymphopoiesis were not caused by a defective marrow
      microenvironment or by abnormal T cells. Our previous studies showed elevated HSA
      expression throughout thymocyte development, which resulted in a profound
      depletion of CD4+CD8+ double-positive and single-positive thymocytes. Together,
      these results indicate that HSA levels can determine the capacity of early T and
      B lymphoid progenitors to proliferate and survive. Therefore, HSA could serve as
      an important regulator during the early stages of B and T lymphopoiesis.

PMID- 8543796
TI  - alpha-Melanocyte-stimulating hormone induces hapten-specific tolerance in mice.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is a proopiomelanocortin-derived
      peptide with known immunoregulatory effects, acting mainly via modulation of
      cytokine secretion by lymphocytes and monocytes. When applied epicutaneously,
      alpha-MSH inhibits both induction as well as elicitation of contact
      hypersensitivity (CHS) responses in mice. We questioned whether systemically
      administered alpha-MSH leads to the induction of hapten-specific tolerance. For
      this purpose, mice were injected i.v. with 75 microgram/kg synthetic bioactive
      alpha-MSH 2 h before sensitization (day 0) or challenge (day 6) with the hapten,
      trinitrochlorobenzene (TNCB). Intravenous administration of alpha-MSH 2 h before
      sensitization or 2 h before challenge resulted in a markedly reduced CHS
      response. To distinguish between unresponsiveness and tolerance, these mice were
      sensitized and challenged a second time, but in the absence of alpha-MSH. Mice
      that had been injected with alpha-MSH before the first sensitization (day 0), but
      not before challenge (day 6), were also unable to develop a significant CHS
      response after an additional sensitization and challenge with the same Ag 10 to
      14 days later. In contrast, sensitization to the unrelated hapten,
      dinitrofluorobenzene, was unaffected in these mice, indicating the induction of
      hapten-specific tolerance by alpha-MSH. Moreover, regional lymph node cells
      obtained from alpha-MSH-treated mice 5 days after resensitization failed to
      produce IL-2 in response to trinitrobenzosulfonic acid, the water-soluble
      analogue of TNCB, whereas lymph node cells from TNCB-sensitized, not alpha-MSH
      treated, mice as well as from mice treated with alpha-MSH before challenge
      readily exhibited trinitrobenzosulfonic acid-specific IL-2 production in this
      assay. Finally, in vivo tolerance induction by alpha-MSH could be abrogated by
      the administration of anti-IL-10 Ab at the site of sensitization. These data
      indicate that alpha-MSH, in addition to its suppressive effect on induction and
      elicitation of CHS, is able to induce hapten-specific tolerance in mice. Thus,
      alpha-MSH may be a significant regulatory mediator of cutaneous immune responses
      in vivo.

PMID- 8543798
TI  - flk2/flt3 ligand is a potent cofactor for the growth of primitive B cell
      progenitors.
AB  - We have investigated the role of flk2/flt3 ligand (FL) in B cell lymphopoiesis.
      The ability of FL to stimulate the growth of immature B cells was assessed using
      distinct populations: CD43lowB220+ pre-B cells, CD43+B220+ pro-B cells, and
      CD43+B220low progenitors. FL failed to affect the growth of the pro-B or pre-B
      cells whether used alone or in combination with stem cell factor (SCF) or IL-7.
      In striking contrast, FL was a potent cofactor for the CD43+B220low progenitor
      cells, interacting with either IL-7 and/or SCF to stimulate their growth. The
      combination of FL with IL-7 plus SCF stimulated maximum expansion of these cells,
      albeit, less than that stimulated in stromal cell cultures. When the CD43+B220low
      progenitors were divided based on expression of heat stable Ag (CD24) into a CD24
      and a CD24+ subset, the FL-responsive cells were contained only within the CD24-
      subset. FL interacted with SCF or with IL-7 to stimulate their growth resulting
      in a 20- and 50-fold increase in cellularity, respectively. Since the CD24-
      subset was the most immature of the B cell populations studied, our data suggest
      that FL costimulates the expansion of very primitive B cell progenitors.

PMID- 8543800
TI  - A dual role for both CD40-ligand and TNF-alpha in controlling human B cell death.
AB  - Members of the TNF-R family are instrumental in controlling lymphoid cell death
      and survival. A major role in the regulation of murine and human B cell survival
      and differentiation has been attributed to CD40/CD40-ligand (CD40-L)
      interactions, but recent in vitro and in vivo data implicate that other receptor
      ligand pairs might also be involved. We have used the human Burkitt lymphoma cell
      line Ramos as a model system to identify additional TNF-R/TNF family members that
      are implicated in the regulation of B cell apoptosis. Ligation of B cell receptor
      (BCR) with anti-IgM mAb for 48 h induced apoptosis in approximately 68% of the
      Ramos B cells. Interestingly, not only CD40 mAb but also rTNF-alpha could
      efficiently inhibit BCR-induced B cell death. In addition, activated T cells also
      prevented BCR-triggered apoptosis, and this effect was inhibited completely by a
      combination of blocking Abs against CD40-L and TNF-alpha. In contrast to the
      strong effect of BCR ligation, APO-1 mAb induced apoptosis in only +/- 18% of the
      Ramos cells after 48 h. Noticeably, addition of CD40 mAb or rTNF-alpha increased
      the percentage of cells (+/- 46%) undergoing apoptosis, which correlated with an
      increase of Fas/APO-1 membrane expression induced by CD40 or TNF-R ligation.
      Taken together, we show that CD40/CD40-L and TNF-R/TNF-alpha interactions not
      only postpone or prevent B cell death, but are also involved in sensitizing B
      cells for Fas-ligand (Fas-L)-dependent death.

PMID- 8543799
TI  - Activation of type I protein kinase A during receptor-mediated human T lymphocyte
      activation.
AB  - The experiments reported herein have characterized the signaling pathway leading
      to stimulation of type I protein kinase A isozyme (PKA-I) activity during the
      early events of Ag receptor-mediated T cell activation. Inhibitor studies
      demonstrated that receptor-initiated activation of nonreceptor protein tyrosine
      kinases, phosphorylation and activation of phospholipase C-gamma 1, and
      activation of protein kinase C occur temporally and precede PKA-I activation.
      Bypass of both the TCR/CD3 complex and IL-1R and direct activation of protein
      kinase C by a phorbol ester can also activate PKA-I. To confirm that PKA-I
      activation via the TCR/CD3 complex and IL-1R requires antecedent protein tyrosine
      kinase-catalyzed phosphorylation of phospholipase C-gamma 1, we used wild-type
      and CD45-deficient (mutant J45.01) Jurkat T cell lines. Unlike wild-type Jurkat T
      cells, the absence of CD45 tyrosine phosphatase resulted in the failure of
      receptor-mediated activation of PKA-I activity and of IL-2 mRNA transcription in
      the mutant J45.01 Jurkat cell line. In conclusion, our data support the concept
      that a signal derived from ligand binding to both the TCR/CD3 complex and IL-1R
      receptor mediates rapid activation of the PKA-I isozyme in primary T lymphocytes
      by sequential activation of an intracellular pathway comprised of CD45
      phosphatase/protein tyrosine kinase/polyphosphoinositide/Ca2+/protein kinase C
      pathway rather than via the conventional surface receptor/stimulatory G protein
      system.

PMID- 8543801
TI  - IL-2 rescues antigen-specific T cells from radiation or dexamethasone-induced
      apoptosis. Correlation with induction of Bcl-2.
AB  - Most studies of apoptosis on T lymphocytes have examined the effects of various
      stimuli on immature T cells from the thymus. Previous work has indicated that
      apoptosis of mature memory T cells may be an important pathophysiologic mechanism
      in diseases such as AIDS, cancer, and autoimmunity. The effect of IL-2 on
      apoptosis of T cells is not clear. Therefore, we studied the ability of IL-2 to
      rescue Ag-specific T cells from apoptosis. We found that IL-2, in a dose
      dependent manner, prevented T cells from entering apoptosis induced by gamma
      irradiation, mitomycin C, or dexamethasone. This effect was specific for IL-2; IL
      1 beta, IL-6, or IFN-gamma could not reproduce it. In contrast to Ag-specific T
      cells, immature T cells and naive mature peripheral T cells could not be rescued
      by IL-2 from radiation-induced apoptosis. Apoptosis rescue by IL-2 was associated
      with the induction of bcl-2 mRNA and protein. This induction could not be
      attributed to the effects of IL-2 on the cell cycle, as T cells that were
      prevented from cell cycle progression by irradiation showed a similar induction
      of bcl-2. Rescued cells retained their Ag-specific proliferative capacity and in
      vivo functions. These findings demonstrate that the apoptotic death of Ag
      specific T cell lines, cells which can be regarded as a model for memory T cells,
      can be prevented with IL-2. This effect may have important therapeutic
      implications for patients receiving chemotherapy or radiotherapy, and for
      patients with AIDS who develop immunodeficiency primarily as a result of loss of
      Ag-specific memory T cells.

PMID- 8543802
TI  - Selective activation-induced apoptosis of peripheral T cells imposed by
      macrophages. A potential mechanism of antigen-specific peripheral lymphocyte
      deletion.
AB  - The self-reactive T cells that escape clonal deletion in the thymus must be
      suppressed by the less well characterized process of peripheral tolerance. In
      this study, we show that monocyte-derived macrophages (M phi) undergoing terminal
      differentiation in the presence of macrophage CSF (M-CSF) acquire the ability to
      selectively induce apoptosis of T cells in an activation-specific fashion.
      Lymphocytes were stimulated via the TCR using anti-CD3 cross-linking,
      staphylococcal superantigen, or allogeneic mixed-leukocyte cultures. T cells
      activated while in contact with M-CSF-derived M phi exited the resting G0 state
      and re-entered the cell cycle, but experienced a sustained arrest near the first
      G1/S transition, followed by progressive apoptosis. In contrast, lymphocytes that
      were not stimulated remained viable, and could later activate normally when
      removed from contact with M phi. Functionally, exposure of T cells to
      alloantigens presented by M-CSF-derived M phi resulted in a selective depletion
      of the alloresponsive T cell population, while preserving reactivity to other
      mitogens and to alloantigens from different donors. The ability of M phi to
      impose activation-induced apoptosis on lymphocytes was regulated developmentally,
      being absent in fresh monocytes, progressively acquired during differentiation in
      M-CSF, and abrogated if monocytes were exposed to IFN-gamma before
      differentiation. We speculate that this novel interaction may help to selectively
      delete autoreactive T cells that respond to self Ags presented by noninflammatory
      tissue M phi.

PMID- 8543803
TI  - Ubiquitin-like moiety of the monoclonal nonspecific suppressor factor beta is
      responsible for its activity.
AB  - Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine
      T cell hybridoma, possesses pleiotrophic Ag-nonspecific suppressive functions.
      Most recently, a cDNA clone encoding MNSF beta (a subunit of MNSF) was isolated
      and characterized. The MNSF beta cDNA encodes a 14.5-kDa fusion protein with MNSF
      like activity consisting of an 8-kDa ubiquitin-like segment (ubi-L) and the
      ribosomal protein S30 (6.5 kDa). To determine whether ubi-L itself has biologic
      activity, cDNA encoding the ubi-L region was expressed in bacteria and the
      recombinant product was tested for the activity. Ubi-L showed MNSF-like biologic
      activity without any cytotoxic action. Interestingly, the addition of ubiquitin
      to the assay inhibited ubi-L-induced suppression. IFN-gamma, which is known to
      enhance the expression of MNSF receptor, induced splenocytes to secrete ubi-L by
      increasing mRNA. Ubi-L has species-specific action and the ability to selectively
      inhibit the B cell proliferative response stimulated by soluble but not by
      Sepharose-bound anti-Ig Ab. In addition, okadaic acid, a serine/threonine
      phosphatase 1 and 2A inhibitor, showed a synergistic inhibitory action with ubi
      L, indicative of the possible involvement of phosphatase(s) in the regulation of
      ubi-L action.

PMID- 8543804
TI  - Regulation of the catalytic subunit (p34PSK-J3/cdk4) for the major D-type cyclin
      in mature B lymphocytes.
AB  - We examined the expression of the cyclin-dependent kinase 4, p34PSK-J3/cdk4
      protein, in small dense, activated, and proliferating primary B lymphocytes. A
      small steady state level of cdk4 synthesis was detected in resting B cells.
      Stimulation of resting B cells with mitogenic amounts of F(ab')2 fragments of
      goat anti-mouse IgM (anti-Ig) resulted in increased synthesis of cdk4 protein
      during the mid to late G1 phase of the cell cycle; LPS or the combination of
      phorbol ester and calcium ionophore also elevated cdk4 levels. Resting B cells
      that we rendered competent by treatment with IL 4 or low doses of anti-Ig or,
      alternatively, were activated by phorbol ester or ionomycin alone also exhibited
      heightened cdk4 protein levels. Subsequent analysis of potential cdk4 regulatory
      subunit D-type cyclins revealed that cyclin D2, not cyclin D1 or D3, is expressed
      in primary mature B lymphocytes. The induction of cyclin D2 synthesis in response
      to mitogenic anti-Ig paralleled cdk4 expression; however, IL-4 or low dose anti
      Ig alone did not increase the rate of de novo cyclin D2 synthesis above that of
      resting B cells. The significance of the lack of cyclin D2 regulation by
      competence-inducing growth factors was demonstrated, in that only mitogenic
      factors that stimulated DNA synthesis 1) led to the formation of stable cyclin
      D2/cdk4 holoenzyme complexes during G1 phase progression, and 2) afforded the
      isolation of anti-cyclin D2 or anti-cdk4 immunoprecipitates that phosphorylated
      retinoblastoma. These findings suggest a role for these proteins during the mid
      to late G1 phase progression and possibly the G1/S phase transition in primary
      mature B lymphocytes.

PMID- 8543805
TI  - pim-1 proto-oncogene expression in anti-CD3-mediated T cell activation is
      associated with protein kinase C activation and is independent of Raf-1.
AB  - We have studied pim-1 proto-oncogene expression in human T cell responses to Ag
      receptor-generated signals. The pim-1 gene encodes a serine/threonine protein
      kinase that is expressed primarily in cells of hematopoietic lineage and is
      implicated in the intracellular signaling processes accompanying lymphocyte
      activation. We show here that pim-1 mRNA expression is rapidly induced after
      receptor cross-linking with anti-CD3 Abs. We examined the linkage of pim-1
      expression to known signaling pathways generated through the T cell Ag receptor.
      pim-1 mRNA was not substantially induced after elevation of intracellular free
      Ca2+. In contrast, PMA, which directly activates PKC, induced rapid pim-1
      expression. Further, anti-CD3- or PMA-induced pim-1 expression was markedly
      reduced by various PKC inhibitors and by deficiency of the PKC epsilon isoform in
      a mutant T cell line. Thus, T cell Ag receptor-linked pim-1 expression appears to
      be coupled to the PKC component of transmembrane signaling. Because the
      activation of protein kinase C has been shown to activate Raf-1 kinase activity,
      the involvement of Raf-1 in pim-1 expression was also investigated using a human
      T cell line stably transfected with an inducible Raf expression vector. Although
      the overexpression of activated Raf was shown to cause a substantial increase in
      IL-2 expression, no discernible effects on pim-1 were apparent. In addition, we
      examined transcriptional and post-transcriptional mechanisms involved in PKC
      mediated pim-1 expression and observed that both transcriptional and post
      transcriptional mechanisms are coordinately involved in the up-regulation of the
      pim-1 proto-oncogene.

PMID- 8543806
TI  - IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial
      DNA and oligodeoxynucleotides.
AB  - Lymphocyte recognition of characteristic structural features in microbial DNA may
      contribute to immune defense by promoting protective immune responses. The
      dinucleotide CpG is significantly under-represented in vertebrate DNA and is
      usually methylated. In contrast, CpG dinucleotides are generally present at the
      expected frequency in bacterial DNA and are unmethylated. These unmethylated CpG
      motifs induce B cells to secrete IL-6 and IgM, and can induce NK and CD4+ T cells
      to produce the immunoregulatory Th1 cytokine, IFN-gamma. IFN-gamma inhibits IgM
      secretion that is triggered by a different bacterial product, LPS. The present
      study demonstrates that in contrast to its antagonistic interaction with LPS, IFN
      gamma causes a dose-dependent increase in the level of IgM secretion induced by
      CpG DNA. Like IgM secretion, B cell secretion of IL-6 more than doubles after the
      addition of exogenous IFN-gamma. Mice with disrupted IFN-gamma genes produced
      less than half as much IL-6 and IgM in response to CpG DNA, supporting the
      hypothesis that CpG-induced IFN-gamma production contributes to the B cell
      response. In contrast to its promotion of IL-6 and IgM secretion, IFN-gamma did
      not significantly affect the spleen cell proliferation activated by CpG motifs.
      These results indicate that IFN-gamma produced by T and NK cells after CpG DNA
      stimulation contributes to the B cell production of IL-6 and the subsequent Ig
      production. These studies provide further evidence that the immune system
      responds to CpG motifs in bacterial DNA by activating a coordinated set of
      humoral and cellular responses.

PMID- 8543807
TI  - Endoglin is a component of the transforming growth factor (TGF)-beta receptor
      complex of human pre-B leukemic cells.
AB  - Endoglin was first identified on a cell line derived from pre-B acute
      lymphoblastic leukemia. This 180-kDa homodimeric glycoprotein was then shown to
      be primarily expressed on endothelial cells and to bind the beta 1 and beta 3
      isoforms of TGF-beta with high affinity. We now demonstrate that pre-B leukemic
      cells express a functional TGF-beta 1 receptor complex. The levels of mRNA for
      these receptors and for TGF-beta 1 were quantitated by PCR. HOON, G2, and NALM-6
      cell lines express similar levels of mRNA for TGF-beta 1 and for TGF-beta
      receptor I (R-I) and receptor II (R-II). HOON cells express ten times more
      endoglin than G2 and NALM-6 cells, whereas all three cell lines have low levels
      of betaglycan relative to other cell types. The receptors were identified by
      affinity labeling with 125I-labeled TGF-beta 1, chemical cross-linking, and
      specific immunoprecipitation. Endoglin, R-II, and R-I were co-precipitated by Abs
      to either endoglin or R-II, indicating that these proteins are forming a receptor
      complex on leukemic cells; no betaglycan could be immunoprecipitated. The
      receptor complex is functional, as demonstrated by inhibition of proliferation of
      HOON cells (80%) and NALM-6 cells (60%) with 25 pM TGF-beta 1. Furthermore, the
      motility of HOON and NALM-6 cells on immobilized fibronectin, which appears to be
      alpha 4 beta 1-integrin mediated, was stimulated two- to threefold by TGF-beta 1.
      These results suggest that active TGF-beta 1 produced in the bone marrow
      microenvironment might stimulate the motility of normal pre-B cells and the
      peripheral dissemination of leukemic pre-B cells.

PMID- 8543808
TI  - Functional dissociation of CD8 alpha's Ig homologue and connecting peptide
      domains.
AB  - The contribution of the CD8 alpha.IgV homologue domain to class I MHC binding was
      evaluated using a series of chimeric human CD8 alpha:Fc polypeptides
      incorporating alternative CD8 alpha extracellular domain components. Using a
      nonisotopic cellfree physical binding assay, those Fc chimeras encompassing the
      CD8 alpha.IgV homologue domain only (dissociated from the 48-amino acid CD8 alpha
      connecting peptide) were shown to retain the capacity of the complete CD8 alpha
      extracellular domain to bind to a recombinant soluble class I MHC alpha 3 domain
      unit or to intact class I MHC. The specificity of the CD8 alpha:class I MHC alpha
      3 domain interaction was verified by mAb and soluble polypeptide blocking
      experiments. Furthermore, co-precipitation of an Fc chimera incorporating only
      the CD8 alpha.IgV homologue domain and a recombinant soluble class I MHC alpha 3
      domain unit was accomplished. In addition, a glycosylphosphatidylinositol (GPI)
      modified variant of the CD8 alpha.IgV homologue domain was generated via
      chimerization with the GPI signal sequence from decay-accelerating factor. GPI
      anchorage for this truncated CD8 alpha polypeptide was verified, and its capacity
      to promote intercellular adhesion through class I MHC binding was shown in a
      cell:cell binding assay. The findings indicate that the CD8 alpha.IgV homologue
      domain acts as an independent structural unit when dissociated from the CD8 alpha
      connecting peptide, and in so doing retains class I MHC binding capacity. This
      further establishes the principle that Ig superfamily domains from
      receptor:counter-receptor pairs can interact with each other as isolated units,
      providing an experimental path for tailoring therapeutically useful IgSF protein
      derivatives.

PMID- 8543809
TI  - The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding
      proteins, highly conserved in human and mouse.
AB  - The Ikaros gene is an essential regulator in the development and homeostasis of
      the mouse lymphopoietic system. To study the role of the Ikaros gene in the human
      lymphopoietic system, we cloned and characterized human Ikaros cDNAs. In the
      human, as in the mouse, differential splicing of Ikaros primary transcripts
      generates a family of lymphoid-restricted zinc finger DNA binding proteins,
      highly conserved in sequence composition and relative expression to the mouse
      homologues. Expression of Ikaros isoforms is highly restricted to the
      lymphopoietic system and is particularly enriched in maturing thymocytes. The
      Ikaros gene maps at a syntenic locus located on the short arm of human chromosome
      7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr).
      The high degree of conservation of the Ikaros gene at the genetic and expression
      levels strongly suggests that it plays a fundamental role in the ontogeny of the
      lymphopoietic system across species.

PMID- 8543810
TI  - Sea urchin genes expressed in activated coelomocytes are identified by expressed
      sequence tags. Complement homologues and other putative immune response genes
      suggest immune system homology within the deuterostomes.
AB  - To identify some of the genes expressed in LPS-activated coelomocytes, we
      sequenced randomly chosen clones from a directionally constructed cDNA library to
      produce a set of expressed sequence tags (ESTs). Deduced amino acid sequences
      from 307 ESTs were compared with known protein sequences in GenBank, and
      significant matches to approximately 30% of the clones were identified. Eighty
      nine clones matched to 55 different proteins, including several putative immune
      effector proteins. In this work, we show the first identification of an
      invertebrate homologue of a vertebrate C component. Another EST matches to
      several short consensus repeats that are characteristic of a variety of proteins,
      including CR/regulatory proteins and clotting factors. Additional putative immune
      effector genes include 1) a Kazal-type protease inhibitor that may function to
      inactivate bacterial proteases, 2) a C-type lectin similar to echinoidin, and 3)
      a serine protease with similarities to thrombin, elastase, haptoglobin, and
      plasmin. Other EST categories include 1) cell surface proteins and receptors, 2)
      proteins involved in signaling systems, 3) lysosomal and secreted proteins, 4)
      cytoskeletal and cytoskeletal modifying proteins, 5) general cell function
      proteins, 6) proteins with unknown function, and 7) ESTs without significant
      matches, 25 with open reading frames. Many of the ESTs identified in this study
      represent the types of genes expected to be used in lower deuterostome immune
      functions.

PMID- 8543811
TI  - Quantitative analysis of the expression of the HLA-DRB genes at the
      transcriptional level by competitive polymerase chain reaction.
AB  - In addition to polymorphism of the peptide-binding site, the density of the MHC
      class II molecules expressed on the membrane of APC could well play a significant
      role in the MHC-peptide-TCR interaction during the immune response. We therefore
      investigated the regulation of the expression of the HLA-DRB genes at the
      transcriptional level. A competitive PCR approach was used to estimate the
      quantities of the HLA-DRB transcripts in peripheral blood B cells. When comparing
      the amounts of steady-state mRNAs among the different DRB1 alleles, the DRB1
      transcripts in the DR52 haplotype group were found to be 2.5 to 3.5 times more
      abundant than the DRB1*01 transcripts, 1.5 to 2 times more abundant than the
      DRB1*04 transcripts, and 7 times more abundant than the DRB1*08 transcripts.
      Within the DR52 haplotype group, the DRB1 and DRB3 transcripts had the same
      abundance. Taken together, these results are in good agreement with the
      previously reported transcriptional activities of the DRB promoters except for
      DRB1*04, thus suggesting a differential post-transcriptional regulation among the
      DRB1 mRNAs.

PMID- 8543812
TI  - A powerful new technique for isolating genes encoding cell surface antigens using
      retroviral expression cloning.
AB  - cDNA expression cloning using retroviral vectors provides a means of stably
      introducing genes into target cells at efficiencies that surpass those achieved
      by transfection. Furthermore, retroviral vectors allow for the introduction and
      expression of complex cDNA libraries in a wide range of cell types, including
      cells of hemopoietic origin. Here we report a novel method for rapidly isolating
      genes encoding cell surface molecules (CSM) from a human bone marrow stromal cell
      cDNA library constructed in the retroviral vector, pRUFneo. With a newly
      described, highly efficient selection strategy using mAb and Ab-coated magnetic
      beads, we have successfully isolated six cDNA encoding previously defined CSM,
      including beta 1 integrin and endoglin. Moreover, we have used this approach to
      define the gene and hence the CSM identified by three previously unclustered mAb.
      These results confirm previous studies demonstrating the general utility of
      retroviral cDNA libraries and further extend their use to the expression cloning
      of cDNA encoding CSM.

PMID- 8543813
TI  - Rhinovirus enters but does not replicate inside monocytes and airway macrophages.
AB  - Potential interactions between rhinovirus (RV) and both the airway macrophage and
      its precursor cell, the blood monocyte, were investigated in terms of direct
      binding, intracellular replication, cell survival, and cytokine production. When
      HeLa cell suspensions are inoculated with RV as a positive control, virus titer
      increases by 100-fold in the first 24 h, confirming intracellular replication. In
      contrast, RV titer in monocyte and macrophage suspensions steadily decreased.
      Despite a lack of productive RV replication, cell-associated RV RNA was
      detectable using a biotin-labeled cDNA probe as early as 6 h after inoculation.
      Direct binding of RV16 to macrophages was confirmed using radiolabeled virus,
      although preincubation with anti-ICAM-1 mAb did not block this interaction.
      Synthesis of RV RNA, as indicated by [3H]uridine incorporation in actinomycin D
      treated cells, was detected in HeLa cells but not macrophages, suggesting that
      the viral RNA detected inside macrophages was from input virus and was not newly
      synthesized. RV inoculation did not adversely affect monocyte or macrophage
      viability. Finally, RV caused macrophage activation, as indicated by the
      induction of TNF-alpha secretion. These in vitro findings suggest that
      macrophages interact with major group RV in vivo, and raise the possibility that
      there is a second cellular receptor for these viruses. Furthermore, macrophages
      do not serve as permissive host cells during in vivo RV infection, but instead
      may be active participants in anti-RV immunity and RV-induced airway
      inflammation.

PMID- 8543814
TI  - Down-regulation of T lymphocyte activation in vitro and in vivo induced by
      glycoinositolphospholipids from Trypanosoma cruzi. Assignment of the T cell
      suppressive determinant to the ceramide domain.
AB  - The major surface glycoinositolphospholipid (GIPL) from Trypanosoma cruzi was
      purified and assessed in mouse T cell function assays. Purified GIPLs from T.
      cruzi strains Y and G, but not from a plant trypanosomatid (Phytomonas serpens),
      markedly blocked in vitro CD4+ and CD8+ T cell mitogenesis induced by bacterial
      superantigen and anti-TCR;CD3 Abs. Secretion of IL-2, but not of IL-4,
      bioactivity, was reduced by GIPLs. T. cruzi, but not P. serpens, GIPL also
      blocked recall cellular responses to T. cruiz. GIPLs from T. cruzi, but not from
      P. serpens, blocked in vivo regional lymph node T cell activation induced by anti
      CD3 mAb. Blockage led to loss of IL-2 responsiveness, with inhibition of CD25
      expression on both CD4+ and CD8+ subsets. Isolated phosphoinositol
      oligosaccharides from GIPLs had no effect on in vitro CD4+ T cell mitogenesis.
      Isolated ceramide from T. cruzi GIPLs contained mainly N
      lignoceroyldihydrosphingosine and blocked CD4+ T cell activation in vitro with
      the same potency as the intact GIPL. Standard N-palmitoylsphingosine, but not N
      palmitoyldihydrosphingosine, blocked CD4+ T cell mitogenesis. A longer fatty acid
      chain, such as in standard N-lignoceroyldihydrosphingosine, or in the natural
      trypanosomal GIPL-derived ceramide, however, conferred full inhibitory effects on
      CD4+ T cells. These results demonstrate that T. cruzi GIPL has T cell
      immunomodulatory activity in vitro and in vivo, and that this novel activity maps
      to the ceramide domain. These findings could have implications for immunologic
      disturbances induced in the host by the causative agent of Chagas' disease.

PMID- 8543815
TI  - Production of nitric oxide (NO) is not essential for protection against acute
      Toxoplasma gondii infection in IRF-1-/- mice.
AB  - Production of nitric oxide (NO) by macrophages is important for the killing of
      intracellular pathogens. IFN-gamma and LPS stimulate NO production by
      transcriptional up-regulation of inducible nitric oxide synthetase (iNOS). In the
      present study we used mice with a targeted disruption of the IFN regulatory
      factor-1 gene (IRF-1-/-) to investigate the importance of NO in the host immune
      response against Toxoplasma gondii, a major cause of infection in newborns and
      those with AIDS. IRF-1-/- mice were more susceptible to acute Toxoplasma
      infection, and treatment with either exogenous IFN-gamma or in vivo
      neutralization of endogenous IFN-gamma had little effect on their susceptibility
      to infection. However, administration of exogenous IL-12 was able to prolong
      survival even when IFN-gamma was depleted. An in vivo depletion study suggested
      that the mechanism of this protective response is mediated in part by CD4+ T
      cells. The administration of IL-12 could not overcome the inhibition of
      lymphoproliferative response in T. gondii-infected mice and treatment with N
      monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (iNOS) antagonist in
      vitro was unable to reverse the immunosuppression. In response to Toxoplasma
      infection, splenocytes from IRF-1-/- mice exhibited increased production of IL-10
      as well as a 30-fold increase in its message expression. These studies indicate
      that NO may not be essential for host immunity to the parasite, and moreover that
      IL-12 appears to induce an IFN-gamma-independent mechanism of protection against
      this opportunistic pathogen.

PMID- 8543816
TI  - Pregnancy impairs resistance of C57BL/6 mice to Leishmania major infection and
      causes decreased antigen-specific IFN-gamma response and increased production of
      T helper 2 cytokines.
AB  - Resolution of cutaneous leishmaniasis in infected mice is associated with a
      polarized Th1 immune response by the host, whereas maternal immune responses
      during pregnancy appear to be biased toward humoral (Th2) and away from cell
      mediated (Th1) responses. The objective of this study was to evaluate whether the
      putative Th2 bias in pregnant C57BL/6 mice would impair their normal ability to
      mount a curative Th1 response against Leishmania major infection. Pregnant
      C57BL/6 mice developed larger cutaneous lesions that showed no signs of
      resolution up to 70 days after infection. The infection appeared to be contained
      but not cured, as the footpad lesion remained stable, neither decreasing (as in
      normal C57BL/6 mice) nor showing uncontrolled expansion leading to death (as in
      susceptible mouse strains such as BALB/c). The number of parasites harvested from
      the footpads of pregnant mice was markedly higher than controls throughout the
      course of infection. The increased severity of infection in pregnant mice was
      accompanied by reduced IFN-gamma and increased IL-4, IL-5, and IL-10 production
      by spleen and popliteal lymph node cells stimulated in vitro with Leishmania Ags.
      Furthermore, IgG1 was elevated in the serum of pregnant mice as opposed to an
      increase of IgG2a in infected but nonpregnant controls. These observations
      support the existence of a bias toward Th2 cytokine expression during pregnancy
      and suggest that these cytokines effectively down-regulate the course of a normal
      Th1 response against a parasite infection in the periphery.

PMID- 8543817
TI  - T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases
      implantation failure and fetal resorptions. Correlation with increased IFN-gamma
      and TNF and reduced IL-10 production by placental cells.
AB  - Maternal immune responses can influence fetal survival and several cytokines have
      harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2
      can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However,
      infections such as leishmaniasis show the opposite pattern: resistance is
      associated with the preferential mounting of a Th1 response, whereas a Th2
      response exacerbates the disease. We therefore asked whether the curative Th1
      response against Leishmania major in genetically resistant C57BL/6 mice, would
      compromise concurrent pregnancy. The number of resorptions as assessed by uterine
      scars was significantly increased in infected C57BL/6 mice and this was
      associated with a decreased production by placental cells of the Th2 cytokines IL
      4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the
      frequency of pregnancy failure before implantation in C57BL/6 mice was also
      substantially increased. In contrast to C57BL/6 mice, early infection did not
      reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and
      succumb to infection. For both resorptions and implantations, there appeared to
      be a short period early in infection that was detrimental to pregnancy, followed
      by a period with lesser effects, and a later period that again induced higher
      resorptions or pre-implantation losses. These results suggest that a beneficial
      anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore,
      Th1 cytokines may be deleterious for not only placental maintenance but also
      preimplantation events.

PMID- 8543818
TI  - IL-15 is a novel growth factor for murine gamma delta T cells induced by
      Salmonella infection.
AB  - We have previously shown evidence for the early recruitment of gamma delta T
      cells during the disease course of primary infections with Listeria monocytogenes
      or Salmonella choleraesuis in mice. Since gamma delta T cells at this stage of
      the disease do not produce IL-2, the growth factor for the gamma delta T cells
      remains unknown. IL-15 is a novel cytokine that uses beta- and gamma-chain of IL
      2R for signal transduction, and is produced by activated monocytes/macrophages.
      In this study, we investigated the proliferative activity of IL-15 for gamma
      delta T cells appearing after primary infection with S. choleraesuis 31N-1. The
      gamma delta T cells, which expressed beta- and gamma-chains of IL-2R,
      proliferated in the presence of rIL-15 and produced appreciable levels of gamma
      IFN and IL-4. Addition of anti-IL-2R beta mAb significantly inhibited the IL-15
      induced proliferation of the gamma delta T cells. Furthermore, the gamma delta T
      cells produced gamma-IFN in response to monocyte/macrophage cell line, J774A.1
      infected with S. choleraesuis, which expressed an abundant level of IL-15 mRNA.
      This cytokine production was inhibited significantly by anti-IL-15 Ab. Taken
      together, these results suggest that IL-15 derived from infected macrophages may
      contribute to the early activation of gamma delta T cells during salmonellosis.

PMID- 8543819
TI  - Effects of Mycoplasma fermentans on the myelomonocytic lineage. Different
      molecular entities with cytokine-inducing and cytocidal potential.
AB  - Mycoplasma fermentans is a mycoplasma species that has been accused of serving as
      a cofactor of AIDS development. Here, we show that M. fermentans affects the
      function of human monocytes and myelomonocytic cell lines on at least two
      different levels. Heat-inactivated mycoplasma particles induce inflammatory
      cytokines such as IL-1, IL-6, and TNF in monocytes, as well as in THP-1 cells.
      Moreover, M. fermentans induces IL-10 (but not IL-12) in freshly isolated human
      monocytes. The cytokine-inducing effect is mediated by lipid-associated
      molecules. In addition, we have detected a novel biologic activity that resides
      in the nonlipid-associated protein fraction of M. fermentans (approximate
      molecular mass: 15 to 30 kDa) and that has a cytocidal effect on
      nondifferentiated myelomonocytic cell lines (U937 cells, HL-60 cells), as well as
      on actinomycin-D-sensitized monocytes. Death is accompanied by oligonucleosomal
      DNA fragmentation and loss of chromosomal DNA. U937 and HL-60 cells fail to
      produce cytokines and rather undergo cell death in response to heat-inactivated
      M. fermentans, provided that they are kept in a relatively undifferentiated
      stage. Whereas the cytokine-inducing activity is a general feature of many
      mycoplasma species, it appears that only a restricted panel of mycoplasma species
      exert a cell death-inducing activity. In addition to M. fermentans strains,
      Mycoplasma penetrans, another hypothetical cofactor of AIDS, possess a cytocidal
      activity. This does not apply to other mycoplasma species, including pathogenic
      ones such as Mycoplasma pneumoniae and Ureaplasma urealyticum. The cell death
      inducing effect of M. fermentans is not mediated by cytokines and obeys different
      principles than TNF-alpha-mediated apoptosis. Thus, in contrast to TNF-alpha
      induced death, it is not accompanied by a decrease in the mitochondrial
      transmembrane potential and is not inhibited by preincubation with the
      antioxidant drug N-acetylcysteine. In synthesis, it appears that certain AIDS
      associated mycoplasma species perturb the function and/or generation of cells
      from the myelomonocytic lineage via several distinct pathways.

PMID- 8543820
TI  - Listeria monocytogenes induces apoptosis of infected hepatocytes.
AB  - Infection with blood-borne Listeria monocytogenes results in their early uptake
      by the liver. Foci of hepatocytes become heavily infected and develop into
      microabscesses. Infection results in apoptosis of the hepatocytes. This is
      particularly evident in the edge of the microabscess, where hepatocytes are not
      yet destroyed by the neutrophil. It is also apparent when neutrophils are
      depleted from the circulation. Infection of hepatocytes in culture induces their
      death by apoptosis with the release of neutrophil chemoattractants. Cytokines do
      not reduce the multiplication of Listeria in cultured hepatocytes. This study
      calls attention to an early program of inflammation induced in infected cells
      that are unresponsive to cytokines.

PMID- 8543821
TI  - Two Listeria monocytogenes CTL epitopes are processed from the same antigen with
      different efficiencies.
AB  - Listeria monocytogenes is an intracellular bacterium that elicits MHC class I
      restricted CTL in infected mice. A major CTL specificity is the nonamer peptide
      p60 217-225, which is derived from the bacterial murein hydrolase p60 and
      presented by the H-2Kd MHC class I molecule. In this report, we identify a second
      H-2Kd presented peptide, encompassing residues 449-457 of p60, that is detected
      by L. monocytogenes-specific CTL. Both p60-derived CTL epitopes are good
      competitors for H-2Kd binding and TAP (transporter associated with Ag processing)
      transport. CTL clone WP11.12 lyses L. monocytogenes infected cells and recognizes
      naturally processed p60 449-457 acid eluted from L. monocytogenes-infected
      macrophages. Although both epitopes derive from the same Ag and bind the same
      allelic form of MHC class I, quantitative analysis reveals that the amount of p60
      449-457 in infected cells is approximately 10-fold greater than the amount of p60
      217-225. Shuffling p60 217-225 into position 449-457 decreases its processing
      efficiency, indicating that the large number of p60 449-457 epitopes cannot be
      entirely attributed to epitope-flanking sequences. Our findings indicate that CTL
      epitopes can be processed from Ags with markedly different kinetics and
      efficiencies. Intrinsic qualities of an epitope and its location within a protein
      influence the efficiency of Ag processing.

PMID- 8543822
TI  - Cytokine and chemokine expression in tumors of mice receiving systemic therapy
      with IL-12.
AB  - The cellular and molecular mechanisms of IL-12-mediated anti-tumor activity have
      been examined. BALB/c mice bearing established s.c. RENCA or CT26 tumors that
      were treated daily with IL-12 showed essentially complete tumor regression while
      tumors in untreated animals grew progressively. Examination of inflammatory gene
      expression in tumor tissue from treated vs untreated mice revealed the selective
      expression of IFN-gamma and the IFN-gamma-inducible CXC chemokine IP-10.
      Immunohistologic analysis demonstrated that tumors from treated mice were heavily
      infiltrated with CD8+ T cells and Mac-1+ mononuclear cells. Tumor regression in
      IL-12-treated mice was associated with expression of the lytic effector molecules
      perforin and granzyme B. These findings support the hypothesis that the anti
      tumor function of IL-12 treatment depends upon the induced expression of IFN
      gamma by T cells and/or NK cells, the amplification of the immune response
      mediated by IFN-gamma-induced expression of chemoattractant cytokines, and the IL
      12-dependent potentiation of the cytolytic effector function of recruited CD8+ T
      cells.

PMID- 8543823
TI  - Antigen-specific tumor vaccines. Development and characterization of recombinant
      adenoviruses encoding MART1 or gp100 for cancer therapy.
AB  - The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA
      A2-restricted CD8+ CTLs derived from melanoma patients and appear to be involved
      in tumor regression. In order to develop immunizing vectors for the treatment of
      patients with metastatic melanoma, replication-defective recombinant
      adenoviruses, Ad2CMV-MART1 and Ad2CMV-gp100, which encode these tumor Ags, have
      been generated. Infection of non-Ag expressing HLA-A2+ cell lines A375 and MDA
      231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated
      by specific target cell lysis and release of cytokines, including IFN-gamma, TNF
      alpha, and granulocyte-macrophage-CSF. Sodium butyrate and TNF-alpha can further
      augment adenovirus-mediated transgene expression and increase recognition by
      specific CTLs. Although adenovirus-infected cells expressed the E3/19K protein at
      detectable levels, significant reduction of surface MHC class I expression was
      observed in only 3 of 10 tumor cell lines infected with either Ad2CMV-MART1 or
      Ad2CMV-gp100. Because of the suspected homology between the human MART1 and gp100
      genes and their murine counterparts, we immunized C57BL/6 mice with these
      recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100
      could protect mice from murine melanoma B16 challenge administered intradermally.
      Depletion of CD8+ but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice
      eliminated the protective effect. The anti-gp100 T cells induced by Ad2CMV-gp100
      vaccinated appeared to be responsible for the protection. Thus, these recombinant
      adenoviruses encoding tumor Ags may be useful as vaccines to induce specific T
      cell immunity for cancer therapy.

PMID- 8543824
TI  - IL-5 activates a 45-kilodalton mitogen-activated protein (MAP) kinase and Jak-2
      tyrosine kinase in human eosinophils.
AB  - IL-5 is a member of the hemopoietic cytokine family and has profound effects on
      the differentiation, survival, migration, and effector function of human
      eosinophils. Increased tyrosine phosphorylation has been observed as an early
      event in IL-5 signal transduction in eosinophils; most notably, proteins of 45
      and 135 kDa became tyrosine phosphorylated following IL-5 treatment. Some of
      these phosphotyrosine-containing proteins may represent intermediates in IL-5
      signal transduction pathways. This study demonstrates that Jak-2, a tyrosine
      kinase, is increasingly tyrosine phosphorylated after IL-5 treatment of human
      eosinophils. Furthermore, we found proteins of 42, 44, and 45 kDa immunoreactive
      with anti-mitogen-activated protein (MAP) kinase Abs that are expressed in human
      eosinophils. One of these, the protein of approximately 45 kDa (p45), was
      tyrosine phosphorylated following treatment of eosinophils with IL-5 and PMA, as
      seen by anti-phosphotyrosine immunoprecipitation and immunoblotting with anti-MAP
      kinase Abs. In addition, anti-phosphotyrosine immunoprecipitates of IL-5-treated
      eosinophils contained enhanced phosphotransferase activity toward a myelin basic
      protein (MBP) peptide substrate when compared with control-treated eosinophils.
      In contrast to cytokine-stimulated MAP kinase activation in other cells, there is
      no evidence of tyrosine phosphorylation or enzymatic activation of p42 MAP kinase
      in eosinophils after IL-5 treatment. These data suggest that Jak-2 kinase and an
      activated isoform of MAP kinase, p45, are detected following incubation with IL
      5, and may mediate some of this cytokine's effects on eosinophils in a manner
      unique to the activation pathways previously described for other cells.

PMID- 8543825
TI  - Structural requirements for mucosal vascular addressin binding to its lymphocyte
      receptor alpha 4 beta 7. Common themes among integrin-Ig family interactions.
AB  - The mucosal vascular addressin, MAdCAM-1, is an Ig family adhesion receptor
      preferentially expressed by venular endothelial cells at sites of lymphocyte
      extravasation in mucosal lymphoid tissues and lamina propria. MAdCAM-1 binds the
      lymphocyte homing receptor for Peyer's patches, the integrin alpha 4 beta 7. We
      describe a point mutation within the first Ig domain of MAdCAM-1 that abolishes
      activation-independent alpha 4 beta 7 binding. This point mutation resides within
      an eight-amino acid motif with homology to sequences important for the integrin
      binding ability of the related vascular Ig family members, ICAM-1 and VCAM-1. To
      understand the contributions of the individual MAdCAM-1 domains, chimeric
      exchanges with the beta 1 integrin ligand, ICAM-1, were made. The two N-terminal
      domains of MAdCAM-1 are sufficient to confer alpha 4 beta 7 binding comparable to
      that of native MAdCAM-1. A chimera containing only the N-terminal Ig domain
      (domain 1) of MAdCAM-1 can also bind (to a lesser extent) alpha 4 beta 7, but
      only after integrin (to a lesser extent) alpha 4 beta 7, but only after integrin
      activation. Conversely, the first domain of ICAM-1 appears sufficient to bind
      activated LFA-1. These data suggest that the first domain of MAdCAM-1 is
      sufficient for interaction with alpha 4 beta 7, but that sequences within the
      second domain support this interaction, either by providing additional contact
      points for integrin binding or by contributing to the conformation or
      presentation of the N-terminal domain. The second domain of MAdCAM-1 can also
      support activation-dependent LFA-1 binding to domain 1 of ICAM-1. The findings
      parallel studies of VCAM-1 binding to alpha 4 beta 1 and suggest that structural
      differences exist between vascular Ig-like ligands for alpha 4 vs beta 2
      integrins.

PMID- 8543826
TI  - Human CD38 ligand. A 120-KDA protein predominantly expressed on endothelial
      cells.
AB  - Human CD38, a pleiotropic molecule with ADP-ribosyl cyclase activity, regulates
      activation and growth of several cell types. Its in vivo function is incompletely
      determined, mainly due to the lack of evidence concerning the existence of a
      single or multiple ligands. We recently observed that CD38 rules a selectin-type
      adhesion between lymphoid cells and HUVECs. A panel of murine mAbs raised against
      HUVEC included one (Moon-1) constantly blocking the CD38-mediated adhesion of
      several cell lines to HUVEC. Tissue distribution studies and an extended
      immunohistochemical analysis on the majority of normal human tissues revealed
      that the Moon-1 molecule displays a unique pattern of expression, being present
      at high levels on resting and activated vascular endothelium, on the majority of
      monocytes, platelets, NK cells, and to a lesser extent on T, B, and myeloid
      cells. The Moon-1 structure of an apparent molecular mass of 120 kDa proved to be
      a ligand for human CD38, as inferred by the direct binding observed when using a
      chimeric mouse CD8 alpha-human CD38 (mCD8 alpha-hCD38) molecule as a probe in
      Western blot experiments. Furthermore, Ab-induced modulation experiments
      highlighted an association between the Moon-1 molecule and human CD38 on the
      surface of cell lines coexpressing the two structures, which also share a common
      regulation system of surface expression. Finally, direct ligation of Moon-1 on T
      cell lines caused a relevant increase in the cytoplasmic concentration of calcium
      ([Ca2+]i).

PMID- 8543827
TI  - Induction and regulation of IL-15 expression in murine macrophages.
AB  - IL-15 is a recently described cytokine which resembles IL-2 in its biologic
      activities, stimulating T cell and NK cell proliferation and activation as well
      as enhancing B cell expansion and Ab production. Unlike IL-2, IL-15 is not
      produced by lymphocytes, but instead (at least among cells of the immune system)
      appears to be synthesized primarily by monocyte/macrophages. We have examined the
      induction of IL-15 in murine macrophages (by semiquantitative reverse
      transcriptase-PCR and bioassay) in response to a variety of different macrophage
      activating stimuli and compared the regulation of IL-15 production to that of IL
      12 and TNF-alpha. Optimal induction of IL-15, in each of the macrophages
      populations tested, was found to require both priming (IFN-gamma) and triggering
      (LPS, mycobacteria, or Toxoplasma gondii) stimuli. When compared with IL-12 mRNA
      synthesis by the same macrophages, IL-15.mRNA production was more resistant to
      inhibition by the down-regulatory cytokines IL-14, IL-13, and TGF-beta. Moreover,
      IL-10, which is inhibitory for most other monokines, increased levels of IL-15
      mRNA found after stimulation. These data establish IL-15 as a product of the
      macrophage/monocyte lineage, which is up-regulated on activation. IL-15 could
      thus play an important role in the initiation of immune responses by microbial
      agents.

PMID- 8543828
TI  - Beta-chemokine TCA3 binds to mesangial cells and induces adhesion, chemotaxis,
      and proliferation.
AB  - Specific receptors for the beta-chemokine TCA3 have been identified on mouse
      monocyte/macrophage cell lines and on mouse mesangial cells. Using Scatchard plot
      analysis with 125I-labeled TCA3, a single high-affinity receptor (3-4 nM) was
      identified. Cells of the monocyte lineage express 1,400 to 8,600 TCA3 binding
      sites, while mesangial cells display 40,000 to 49,000 sites/cell. Competitive
      inhibition studies indicated that the TCA3 receptor is unique, although MCP-1, IL
      8, and RANTES were weak competitors of TCA3 binding. We also established the
      functional activity of TCA3 and other chemokines on primary cultures of mouse
      mesangial cells. TCA3 treatment induces increased mesangial cell adhesiveness to
      fibronectin. TCA3 is also a chemoattractant for mesangial cells. In addition,
      TCA3 treatment stimulates [3H]thymidine uptake by mesangial cells. The combined
      results indicate that TCA3 and other chemokines interact with a broader range of
      target cells than previously considered.

PMID- 8543829
TI  - Regulation of complement activity by immunoglobulin. I. Effect of immunoglobulin
      isotype on C4 uptake on antibody-sensitized sheep erythrocytes and solid phase
      immune complexes.
AB  - Intravenous Ig, composed principally of IgG, prevents complement attack by
      inhibiting C3 and C4 uptake onto target cells and tissues. Using two different
      models, Ab-sensitized SRBC and BSA-anti BSA solid phase immune complexes, we have
      examined the complement inhibitory capacity of three Ig classes (IgG, IgM, IgA)
      focussing on inhibition of C4 uptake. It was found that on both a weight and
      molar basis, monomeric serum IgA and IgM were far more active than IgG (weight
      efficiency ratios were 1.0, 20.8, and 236.3, and molar efficiency ratios 1.0,
      24.0, and 1382.9 for polyclonal IgG, IgA1, and IgM, respectively). Monoclonal IgM
      were less active than polyclonal IgM (50% inhibition was achieved in SRBC model
      by 0.022, 0.30, 1.6, and 1.6 mg/ml of polyclonal IgM and monoclonal IgM from
      patients Lew, Will, and Pri). Secretory IgA was less active than serum IgA1 and
      similar in inhibitory activity to IgG (weight and molar efficiency ratios 1.5 and
      0.6 compared with IgG). All tested preparations were less active in the solid
      phase immune complex model than in the sensitized cell model. A mixture of Igs of
      different isotypes was somewhat more active than any isotype alone. These results
      suggest that polyclonal serum IgA and IgM can also be considered for active
      therapy in diseases accompanied by the activation of classical complement
      pathway.

PMID- 8543830
TI  - IL-13 and IL-4 inhibit bone resorption by suppressing cyclooxygenase-2-dependent
      prostaglandin synthesis in osteoblasts.
AB  - Activated T cells secrete the cytokine IL-13, which regulates inflammatory and
      immune responses. To explore the role of IL-13 in bone metabolism, we examined
      the effects of the cytokine on bone resorption and PG synthesis in osteoblasts.
      IL-13 suppressed the bone-resorbing activity stimulated by IL-1 alpha, which was
      determined by the release of 45Ca from prelabeled mouse long bones. Histologic
      examinations revealed that IL-1 alpha markedly stimulated bone resorption with
      increased osteoclast recruitment, and that the simultaneous addition of IL-13
      considerably inhibited it. The gamma-chain of IL-2 receptors may be functionally
      involved in the signal transduction of not only IL-2, but also IL-4, IL-7, and IL
      13. Of these cytokines, IL-4 similarly suppressed IL-1 alpha-induced bone
      resorption, but IL-2 and IL-7 did not. Both IL-13 and IL-4 inhibited PGE2
      production stimulated by IL-1 alpha in long bone cultures. Suppression of IL-1
      alpha-induced bone resorption by IL-13 and IL-4 was recovered by adding exogenous
      PGE2 to the long bone cultures. Neither IL-4 nor IL-13 further inhibited IL-1
      alpha-induced bone resorption in the presence of indomethacin. To examine the
      effects of IL-13 on PG synthesis, we measured the mRNA levels of cytosolic
      phospholipase A2 (cPLA2), constitutively expressed cyclooxygenase (COX-1) and
      inducible COX (COX-2) in mouse osteoblast-like cells. IL-1 alpha markedly
      stimulated the mRNA expression of COX-2, but not that of COX-1. Both IL-13 and IL
      4 dose-dependently suppressed the IL-1 alpha-induced stimulation of both COX-2
      mRNA expression and PGE2 synthesis. A small increase (1.7-fold) in cPLA2 mRNA
      levels was detected in the cultures with IL-1 alpha, but the expression was not
      affected by IL-13 or IL-4. These results indicated that IL-13 and IL-4 inhibit
      bone resorption by suppressing COX-2-dependent PG synthesis in osteoblasts.

PMID- 8543831
TI  - Thioredoxin as a potent costimulus of cytokine expression.
AB  - Reduction/oxidation (redox) processes have been implicated in various biologic
      processes, including signal transduction, gene expression, and cell
      proliferation. Thioredoxin is one of the major redox-regulatory molecules which
      because of its dithiol/disulfide exchange activity determines the oxidation state
      of protein thiols. In this study, we report that treatment of several cell types
      with thioredoxin strongly enhances the expression of various cytokines. In
      monocytic Mono Mac6 cells stimulated with the phorbolester tetradecanoyl
      phorbolacetate (TPA), thioredoxin was found to augment the expression of TNF at
      the protein and mRNA levels. In this and other cell lines, such as fibrosarcoma
      and endothelial cells, thioredoxin also dose-dependently increased the synthesis
      of IL-6. Treatment of TPA-stimulated Mono Mac6 cells resulted in a strong
      potentiation of secreted IL-1 bioactivity and expression of IL-1 alpha and IL-8
      mRNA. In addition, in TPA-activated Molt-4 T cells, an increased expression of IL
      2 and IL-2-specific transcripts was detected. These data demonstrate that
      cytokine synthesis may be tightly controlled by redox-dependent processes. As
      thioredoxin is readily secreted and taken up by cells, it may play an important
      role as a costimulatory molecule involved in immune processes.

PMID- 8543832
TI  - Cellular detachment and deformation induce IL-8 gene expression in human
      bronchial epithelial cells.
AB  - Neutrophil elastase (NE) is known to be one of the most potent proteases capable
      of deforming and detaching human bronchial epithelial cells (BECs) and inducing
      IL-8 gene expression. However, mechanisms of NE-induced IL-8 gene expression are
      unclear, especially with respect to how they relate to cellular detachment. To
      elucidate these mechanisms, effects of cell detachment and deformation following
      mechanical injury or pharmacologic stimuli on IL-8 gene expression were examined
      by Northern analyses. When BET-1A cells from a human bronchial epithelial cell
      line were incubated with NE (100 nM), trypsin (0.5 mg/ml), EGTA (7 mM), or EDTA
      (0.7 mM) to induce deformation and detachment, IL-8 mRNA transcript levels were
      up-regulated, as demonstrated in a case of mechanical detachment from the culture
      plate using a cell scraper. This IL-8 gene expression was inhibited by
      pretreatment with 5 microM taxol, a microtubule-stabilizing agent. Colchicine or
      vinblastine, microtubule-disrupting agents, induced IL-8 gene expression, which
      was also inhibited by taxol treatment. These data suggest that structural
      changes, including deformation of the cytoskeleton, especially microtubules, may
      contribute to IL-8 gene expression in human BECs. Since detachment and cellular
      deformation of BECs caused by proteases have been observed frequently in a
      variety of inflammatory airway diseases, our findings provide evidence that
      detached or deformed BECs potentially enhance production of inflammatory
      mediators in the pathogenesis of airway inflammation.

PMID- 8543833
TI  - Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone
      marrow-derived macrophages.
AB  - The aim of this study was to examine the roles of various cytokines in histamine
      synthesis by macrophages in bone marrow. Pure (> 99% nonspecific esterase-, CD14
      , and Mac-1-positive) macrophage populations were obtained after long term
      culture of bone marrow cells (bone marrow-derived macrophages). Culture of the
      cells in the presence of Escherichia coli LPS caused a slight, but dose
      dependent, increase in histidine decarboxylase-associated histamine synthesis
      with a concomitant increase in the expression of CD14, a LPS receptor, as well as
      the Mac-1 Ag on their surface. Granulocyte/macrophage CSF (GM-CSF) or IL-3
      strongly enhanced LPS-induced histamine formation and expression of CD14 on bone
      marrow-derived macrophages, without affecting the expression of Mac-1 Ag. GM-CSF
      and IL-3 also caused a marked accumulation of both histidine decarboxylase and IL
      6 mRNAs in the cells. Macrophage CSF and IL-1-alpha also potentiated LPS
      dependent histamine formation when it was stimulated with GM-CSF or IL-3. In
      contrast to these cytokines, IFN-gamma suppressed LPS-induced histamine
      production regardless of whether it was stimulated by GM-CSF or IL-3, and
      inhibited CD14 expression. Neither IL-6 nor granulocyte CSF had any appreciable
      effect on LPS-induced histamine production even in combination with GM-CSF or IL
      3. These results suggest that GM-CSF and IL-3 enhance LPS-induced histamine
      production in bone marrow-derived macrophages and that macrophage CSF and IL-1
      alpha augment the actions of GM-CSF and IL-3. Possible implication of CD14
      molecule in the reactions is discussed.

PMID- 8543834
TI  - Signaling by hemolytically inactive C5b67, an agonist of polymorphonuclear
      leukocytes.
AB  - The hemolytically inactive complement component complex C5b67, designated iC5b67,
      can signal human polymorphonuclear leukocytes (PMN) both as a pertussis toxin
      inhibitable agonist for chemotaxis and as an antagonist for C5a- and FMLP
      stimulated chemotaxis and superoxide production. The signaling pathways utilized
      by iC5b67 have been further investigated. In contrast to mastoparan, iC5b67
      failed to directly activate G proteins to stimulate inositol phosphate formation
      in COS cells that had been transfected with G alpha 16. In COS cells co
      transfected with both G alpha 16 and the C5a receptor, iC5b67 could neither
      activate phospholipase C nor inhibit C5a receptor-mediated activation of
      phospholipase C. iC5b67 stimulated GTPase activity in a membrane-enriched
      fraction from PMN. These data support the hypothesis that iC5b67 signals through
      a unique receptor, likely G protein linked, but distinct from the C5a receptor.
      iC5b67 was able to mobilize intracellular stores to elicit increases in
      intracellular Ca2+. Based on the effects of herbimycin A, wortmannin, and
      chelerythrine on iC5b67-induced PMN chemotaxis, iC5b67 signaling involved
      activation of tyrosine and phosphatidylinositol 3-kinases, but not protein kinase
      C. Relevant to the capacity of iC5b67 to antagonize PMN superoxide production,
      iC5b67 induced rapid and sustained increases in intracellular cAMP, which others
      have shown can inhibit superoxide formation. Although iC5b67 antagonizes C5a and
      FMLP receptor-mediated superoxide generation, iC5b67 had no effect on PMA-induced
      superoxide formation. The distinct agonist and antagonist signaling pathways
      activated by iC5b67 in the PMN diverge soon after initial iC5b67 receptor
      mediated transduction steps.

PMID- 8543836
TI  - Self-reactive cytotoxic gamma delta T lymphocytes in Graves' disease specifically
      recognize thyroid epithelial cells.
AB  - In this paper we report the isolation of a self-reactive cytotoxic gamma delta T
      cell line, 158RE.2, that originates from the T lymphocyte population infiltrating
      the thyroid gland of a patient with Graves' disease. Functional data using this
      cell line demonstrate that gamma delta T cells expanded in the thyroid tissue
      specifically recognize a ligand expressed by thyroid epithelial cells and cell
      lines of endocrine epithelial origin. The TCR expressed by these gamma delta T
      cells--V gamma I/V delta 5--is unusual in peripheral blood lymphocytes, and its
      specificity is clearly different from that observed in a high percentage of gamma
      delta T cells from PBL, which express the common TCR V gamma 9/V delta 2. The V
      gamma I/V delta 5 receptor is involved in the recognition of the ligand expressed
      by the thyroid cells, but not in the NK-like activity also displayed by 158RE.2.
      These cells express CD8 alpha alpha dimers, which participate in the thyroid
      ligand recognition but not in the NK-like activity. The epithelial cell
      recognition is not restricted by classical MHC class I or class II molecules,
      although the CD8 alpha alpha participation in the recognition suggests the
      involvement of nonclassical MHC molecules. These are the first data to be
      presented on self-reacting gamma delta T cells in human epithelium.

PMID- 8543835
TI  - T cells, but not thymic exposure to HLA-B27, are required for the inflammatory
      disease of HLA-B27 transgenic rats.
AB  - Rats transgenic for the human MHC class I gene HLA-B27 are susceptible to a
      spontaneous multisystem inflammatory disease that resembles human B27-associated
      disease. This disease requires a high level of expression of the B27 transgene
      product in cells of hemopoietic origin and can be adoptively transferred to B27
      transgenic or nontransgenic rats by transplantation of bone marrow (BM) or fetal
      liver (FL) cells. To investigate the role played by T cells and the thymus in the
      disease process, we produced congenitally athymic rnu/rnu F344 rats carrying the
      disease-prone B27 transgenic locus of the 33-3 line. Transgenic nude rats were
      protected from disease manifestations. This protection was abated by
      reconstitution with T cells from euthymic donors of the 33-3 line, with CD4 T
      cells being more efficient than CD8 T cells in transferring disease. Lethally
      irradiated, adult-thymectomized (ATX), nontransgenic recipients reconstituted
      with intact BM, T cell-depleted BM, FL, or nude BM from syngeneic disease-prone
      lines all developed disease. Pretreatment of the ATX nontransgenic recipients to
      deplete T cells enhanced the subsequent transferred disease. The inflammatory
      disease of B27 transgenic rats is thus T cell-dependent. The relevant T cells do
      not need to encounter B27 in the thymus, and residual radioresistant and/or
      extrathymically derived host T cells are sufficient to mediate the adoptively
      transferred disease. The data are most consistent with a model of B27-mediated
      disease arising from a failure of tolerance and requiring a population of CD4 T
      cells.

PMID- 8543837
TI  - MHC genes modify systemic autoimmune disease. The role of the I-E locus.
AB  - The MHC exerts an important influence on systemic autoimmune disease. In C57BL/6
      lpr/lpr (B6/lpr) mice, substitution of the H-2d instead of the H-2b MHC haplotype
      results in a global reduction in autoantibody levels. Since H-2d expresses both I
      A and I-E, while H-2b expresses only I-A, general down-regulation of autoimmunity
      in the d haplotype might be due to I-E expression. This was tested with I-E alpha
      d transgenic B6/lpr mice, which expressed a functional surface I-E molecule. Five
      month-old transgene-positive B6/lpr mice had much lower total IgG, IgG anti
      chromatin, anti-DNA, and IgM rheumatoid factor directed against IgG1 and against
      IgG2b than transgene-negative littermates (p < or = 0.002), as well as
      significantly lower spleen and lymph node weights (p < or = 0.002). Decreases in
      autoantibody levels in the transgenic lpr mice were not due to a nonspecific
      effect of the I-E alpha d transgene, since transgene-positive B6/lpr.H-2d mice
      had levels of autoantibodies comparable with transgene-negative B6/lpr.H-2d mice.
      To determine whether autoantibody was preferentially made by I-E-negative B
      cells, irradiated (B6/lpr.Igha x B6/lpr.I-E alpha d)F1 mice were reconstituted
      with equal amounts of B6/lpr.Igha and B6/lpr.I-E alpha d bone marrow. Allotype
      specific ELISA showed that most autoantibody was produced by the I-E negative B
      cells (range 97% to 84%). The results show that a functional I-E molecule in lpr
      mice leads to generalized reduction in autoantibody levels through a direct
      effect on the B cell. The molecular mechanism of this effect remains to be
      determined.

PMID- 8543838
TI  - Glutamic acid decarboxylase autoantibodies in stiff-man syndrome and insulin
      dependent diabetes mellitus exhibit similarities and differences in epitope
      recognition.
AB  - Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases,
      insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS). However,
      most individuals with one of these diseases do not have the other disease. Prior
      studies have suggested that the natures of the GAD Abs associated with each of
      these diseases are different, which may have implications for the autoimmune
      pathogenesis. We have compared the GAD autoantibody profile and have mapped GAD
      protein epitope regions in the two diseases using an immunoprecipitation assay
      with recombinant GAD 65 and GAD 67 proteins, GAD protein fragments, and synthetic
      GAD peptides, as well as chimeric GAD proteins. Our results indicate that
      individuals with SMS have GAD Abs in 100- to 500-fold higher titer than
      individuals with IDDM. The population of GAD Abs in SMS sera is quite complex and
      includes those that recognize at least three GAD 65 epitope regions located
      between amino acids 1-16, 188-442, and 442-563. These types of GAD Abs are not
      found in IDDM sera. All SMS sera also had Ab specificity that binds GAD 67 in a
      region highly homologous to amino acids 188-442 of GAD 65. In contrast to prior
      studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera
      also target two conformation-dependent regions of GAD 65, one located in the
      middle and one near the C-terminus of the protein. These two regions of the GAD
      65 protein are similar to regions targeted by GAD 65-specific Abs found in
      individuals with IDDM. These results indicate that although disease-specific
      epitopes may exist, there is also overlap in the humoral response between the two
      diseases.

PMID- 8543839
TI  - CD4-imitating human antibodies in HIV infection and anti-idiotypic vaccination.
AB  - Anti-idiotypic vaccination against HIV infection aims at inducing an anti-gp120
      immune response through anti-CD4 Abs mimicking epitopes of the gp120 molecule.
      The mAb IOT4a induces anti-gp120 Abs in rabbits. This study investigates the
      presence of human serum Abs cross-reacting with anti-CD4 mAbs and gp120 during
      HIV infection and after parenteral vaccination with IOT4a. Ten HIV-infected
      volunteers without immunodeficiency were inoculated s.c. with 0.6, 1.2, or 2.4 mg
      IOT4a. Six booster injections followed until day 35. Sera from study patients, 80
      HIV-positive, and 43 seronegative controls were examined by a panel of assays,
      including an ELISA using competition against biotinylated recombinant CD4, flow
      cytometry assaying inhibition of anti-CD4 mAbs and biotinylated gp120 binding to
      CD4-positive lymphocytes, and an IOT4a immunoblot. After vaccination, an increase
      in competitive binding activity, which was quantitative in ELISA and flow
      cytometry, was observed. In the ELISA, competition against biotin-CD4 was
      quantitatively quenched by preincubating sera with r-gp120 or anti-CD4 mAbs such
      as IOT4a and Leu3a. Naive sera or sera from blood donors had no such effect in
      the assays employed, while 5/80 HIV sera showed binding qualities similar to
      vaccinees. These results suggest that 1) CD4 internal-image Abs emerge in a small
      proportion of HIV-positive individuals, and 2) parenteral vaccination with mAb
      IOT4a can induce a gp120 cross-reacting immune response that inhibits gp120
      binding to CD4.

PMID- 8543840
TI  - Class I-restricted presentation of an HIV-1 gp41 epitope containing an N-linked
      glycosylation site. Implications for the mechanism of processing of viral
      envelope proteins.
AB  - Uncertainty exists over the site of processing of viral envelope (env) proteins
      for recognition by CTL. The extracellular domains of env proteins are not present
      in the cytosol, the site where the class I Ag processing pathway begins. Rather,
      the ecto-domains of env proteins are cotranslationally translocated into the
      endoplasmic reticulum during biosynthesis. To clarify the site of processing of
      viral env proteins, we examined the processing of an HLA B*3501-restricted
      epitope in the extracellular domain of the HIV-1 env protein. Although this
      epitope contains an N-linked glycosylation signal sequence, CTL specific for this
      epitope recognize a nonameric peptide that has not been previously modified by
      attachment of oligosaccharide. This was demonstrated in two ways. First, an env
      specific B*3501-restricted CTL clone recognized a nonglycosylated, synthetic
      nonamer representing the minimal B*3501-restricted epitope, but not the
      glycosylated or deglycosylated forms. Second, the naturally processed, B*3501
      restricted, env peptide is identical with a nonglycosylated, synthetic nonamer.
      Thus, the naturally processed form of an env epitope containing an N-linked
      glycosylation site is derived from env protein that is not glycosylated at the
      relevant asparagine during biosynthesis. Since the addition of N-linked
      oligosaccharides occurs only after the glycosylation signal sequence (N-X-S/T) is
      translocated into the endoplasmic reticulum, the initial processing reaction for
      this epitope may take place in the cytosol. Low-frequency failure of signal
      sequence containing polypeptides to engage the translocation apparatus, resulting
      in synthesis and degradation in the cytosol, may represent an important mechanism
      for the generation of class I-restricted CTL responses.

PMID- 8543841
TI  - IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and acutely
      infected cells of monocyte/macrophage lineage.
AB  - IL-10 is elevated in HIV-1-infected individuals and has been implicated in
      disease progression. In this study, we investigated the effects of IL-10 on the
      activation of HIV-1 from infected monocytes and macrophages. Although IL-10 alone
      did not induce HIV-1 replication, in the presence of TNF-alpha, IL-10 markedly
      enhanced virion production from a chronically infected promonocytic cell line
      (U1) and in acutely infected monocyte-derived macrophages. Neutralizing mAbs to
      IL-10 and TNF-alpha indicated that both cytokines were essential for the
      induction and were required to generate a synergistic increase in virus
      expression. The effects of the two cytokines were distinguishable functionally
      since pretreatment with TNF-alpha attenuated the cytokine cooperativity, while
      pretreatment with IL-10 potentiated their cooperativity, suggesting that IL-10
      and TNF-alpha play different roles in the activation of virus. Northern blot
      analysis as well as Ab blocking and cytokine secretion studies indicated that the
      induction of either endogenous TNF-alpha or IL-10 was not involved in the
      cooperativity, nor was an up-regulation of TNF-alpha receptors. In combination
      with TNF-alpha, IL-10 stimulated activating protein-1 (AP-1) and nuclear factor
      (NF)-kappa B binding activities and cooperated to increase HIV-1 steady-state
      mRNA levels and enhance long terminal repeat-directed transcription through
      activation of the NF-kappa B binding sites, suggesting the IL-10 effect occurs at
      least in part at the transcriptional level. These results indicate that IL-10, in
      addition to down-regulating the cellular immune response to HIV-1, may also play
      a role in TNF-alpha-mediated activation of HIV-1 replication in the
      monocyte/macrophage lineage.

PMID- 8543842
TI  - Oligoclonality of V beta 3 TCR chains in the CD8+ T cell population of rheumatoid
      arthritis patients.
AB  - It has been established that oligoclonal expansion is a common feature of the
      CD8+ T cell population, particularly within the CD8+ CD57+ lymphocyte subset. In
      addition, clonal malignancies involving CD8+ CD57+ T cells (large granulocytic
      lymphocytic leukemias) are often accompanied by rheumatoid arthritis, Felty's
      syndrome, or both. Therefore, to identify disease-related alterations in the CD8+
      T cell repertoire, we have compared the patterns of oligoclonality in the CD8+ T
      cells of rheumatoid arthritis patients (n = 32) with those of age-matched
      controls (n = 25). By using a multiplex PCR assay for the CDR3 length of TCR beta
      chains, we have found a striking increase in the frequency of CD8+ oligoclonality
      involving V beta 3 TCR: 50% of the rheumatoid arthritis patients had evidence of
      oligoclonality in this TCR family compared with 4% of controls (p < 0.0002). In
      addition, two unrelated RA patients had clonally dominant CD8+ T cell beta
      receptors that were identical in amino acid sequence, suggesting selection by a
      common Ag. An analysis of a subset of RA patients with mAbs specific for V beta 3
      TCR revealed the presence of clonal expansion in a minority of patients usually,
      but not exclusively, involving the CD57+ subset. These data define a phenotype of
      the T cell repertoire that is strongly associated with rheumatoid arthritis; the
      mechanisms and genetic and environmental factors that explain this phenomenon
      remain to be defined.

PMID- 8543843
TI  - An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not
      HTLV-I, in a CD4-positive/p56lck-negative HTLV-I-transformed cell line.
AB  - mAbs that bind to the Ig CDR3-like region in D1 domain of the CD4 molecule can
      inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell
      lines at the stage of transcription. This antiviral effect requires the integrity
      of the cytoplasmic tail of CD4, which acts as a signal transduction region
      through its association with protein tyrosine kinases such as p56Ick. Here we
      investigated the role of p56Ick in the cascade of molecular events that control
      HIV-1 transcription in cells treated with anti-CD4 mAb directed against the Ig
      CDR3-like region. The Ig CDR3-like region-specific mAb, 13B8-2, blocked HIV-1
      production in CD4-positive/p56Ick-negative HTLV-I-producing MT2 cells
      superinfected by HIV-1Lai, but had no effect on HTLV-I production, although it
      did inhibit Tax-induced NF-kappa B translocation. These results raise the
      possibility that an as yet unidentified tyrosine kinase may be capable of
      associating with CD4 and mediating intracellular signaling.

PMID- 8543844
TI  - B cells are generated throughout life in humans.
AB  - This analysis of B cell development as a function of age reveals a relatively
      widespread distribution of progenitor B (pro-B), pre-B, and B cells in fetal
      tissues, and thus supports the idea of a multifocal origin of B lineage cells
      during embryonic development. From mid-gestation onward, the bone marrow is the
      major site of B cell generation in humans. A relatively constant ratio of bone
      marrow precursors to B cells of immature phenotype (CD24highCD10+CD20lowIgD-) is
      maintained from mid-gestation through the eighth decade of life. The persistence
      of recombinase gene activity in pro-B cells further attests the sustained
      production of B cells in bone marrow. Interestingly, a subpopulation of B cells
      with mature phenotype (CD24lowCD10-CD20highIgD+) accumulates in the bone marrow
      during childhood, and this becomes the predominant B cell subpopulation in adult
      bone marrow. This mature population of bone marrow B cells may represent a
      subpopulation of recirculating B cells that have undergone selection in the
      periphery.

PMID- 8543845
TI  - Adjuvant-free hsp70 fusion protein system elicits humoral and cellular immune
      responses to HIV-1 p24.
AB  - Heat shock proteins are major targets of the immune response to bacterial and
      parasitic pathogens. Mycobacterium tuberculosis hsp70 is an especially powerful
      Ag containing multiple B and T cell epitopes. We investigated whether M.
      tuberculosis hsp70 can be used as an adjuvant-free carrier to stimulate the
      humoral and cellular immune response to an accompanying protein. A recombinant
      hsp70 protein expression vector was developed that permits the production of any
      protein fused to the amino terminus of mycobacterial hsp70. We found that a
      recombinant HIV p24-hsp70 fusion protein produced with this vector elicited both
      humoral and cellular immune responses against p24 in mice when administered in
      saline in the absence of adjuvant. Covalent linkage of hsp70 to p24 was essential
      to elicit immune responses to p24 under these conditions. The anti-p24 IgG1 Abs
      induced in p24-hsp70-immunized mice persisted at high levels for more than 1 yr
      after immunization. These results demonstrate that the antigenic properties of M.
      tuberculosis hsp70 can be exploited to enhance the humoral and cellular immune
      response to an attached protein.

PMID- 8543846
TI  - [The clinical significance of the ratio in FSH/LH of human menopausal
      gonadotropins in a programmed stimulation regimen for IVF-ET].
AB  - Human menopausal Gonadotropin (hMG) has been used in controlled ovarian
      hyperstimulation (COH) protocol for IVF-ET. We investigated three hMG
      preparations with different FSH/LH ratios to determine their clinical
      effectiveness in a programmed stimulation regimen for IVF-ET. Eighty-four IVF-ET
      candidates at Toho University Hospital received injections of an hMG preparation
      containing a 3:1 ratio of FSH/LH: Group A, 36 patients received hMG at an FSH/LH
      1 : 1 ratio: Group B, and 20 patients receive pure FSH : group C. All received
      injections of 300IU hMG daily for 7 days according to our COH protocol (=7-day
      schedule). Analysis determined the serum levels of E2, number of mature
      follicles, number of retrieved oocytes, fertilization rate, cleavage rate, number
      of transferred embryos and pregnancy rate. The results were as follows: 1. The
      serum E2 level was higher in Group A than in Group C with significant
      differences. 2. The oocyte retrieval rate was significantly higher in Group A. 3.
      The rate of equally cleaved eggs was significantly higher in Group A. 4. The
      pregnancy rate was significantly higher in Group A. In conclusion, an hMG
      preparation containing a 3 : 1 FSH/LH ratio was most suitable in our COH
      protocol.

PMID- 8543847
TI  - [A study of interleukin-6 and soluble interleukin-6 receptors during pregnancy
      and delivery].
AB  - In order to investigate the correlation between uterine contraction and
      Interleukin-6 (IL-6), we studied the effects of the prenatal course and uterine
      contraction on IL-6 and the soluble Interleukin-6 receptor (sIL-6R) concentration
      in human amniotic fluid. We also determined the effects of IL-6 on the
      permeability of the human amnion cell monolayer. The results were as follows: 1)
      The level of IL-6 at full term delivery was significantly higher than that at
      premature delivery. 2) The level of IL-6 without uterine contraction was
      significantly (p < 0.05) higher than that with uterine contraction. 3) The mean
      sIL-6R value at full term delivery was 1.28 +/- 0.21 ng/ml. There was no
      correlation between sIL-6R and the prenatal course. 4) IL-6 enhanced permeability
      in the human amniotic cell monolayer. This effect of Il-6 was concentration
      dependent and time dependent. These results show that uterine contractions
      increased the IL-6 concentration in human amniotic fluid, and suggest that
      uterine contraction enhanced the permeability of the human amniotic cell in vivo.

PMID- 8543848
TI  - [Effect of ritodrine hydrochloride on fetal perfusion pressure in dually perfused
      human placenta].
AB  - Ritodrine hydrochloride is widely used in clinical obstetrics for the prevention
      of premature labor, but the knowledge of its effect on fetal circulation is
      limited. The purpose of this study was to elucidate changes in vascular
      resistance in the fetal placental circulation by using the dually perfused human
      placenta in vitro. The viability of the perfused placenta was maintained during
      the experiments because the production rate of hCG was constant. The transfer of
      ritodrine hydrochloride was observed and its concentration on the fetal side was
      about one third of maternal side at 120 min subsequent to the injection. The
      fetal perfusion pressure during the control period was 38.6 +/- 7.0 mmHg (mean +/
      S.D., n=3). After the addition of ritodrine hydrochloride to the maternal
      circulation, the fetal perfusion pressure was decreased dose-dependently. The
      pressure was 95.4 +/- 1.8% at 80 ng/ml of ritodrine hydrochloride which was
      within the clinical concentration limits. It is concluded that ritodrine
      hydrochloride acts as a vasodilator on the fetal vasculature in the human
      placenta.

PMID- 8543849
TI  - [The perinatal risk factors of periventricular leukomalacia (PVL) in premature
      infants].
AB  - Periventricular leukomalacia (PVL) has recently been recognized as an important
      risk factor in neurological impairment of the premature infant. We studied 29 PVL
      cases concerning perinatal risk factors retrospectively comparing them with a non
      PVL matched control group. Variable decelerations were more frequently observed
      with statistical significance in the PVL group in the intrapartum period. There
      was no significant difference between the two groups in the appearance of late
      deceleration. A lower incidence of RDS, a higher incidence of low Apgar score, a
      longer period of ventilation and oxygen inhalation and a more persistent presence
      of apneic spells were documented in the PVL group with statistical significance.
      Our study suggests the significance of variable deceleration as a risk factor in
      the occurrence of PVL in premature infants as well as other previously documented
      risk factors.

PMID- 8543850
TI  - [mRNA expression and protein localization of placental tissue protein 11, 12, 19
      in gynecologic malignant tumors].
AB  - In recent years, the localization and function of placental tissue proteins
      (PPs), extracted by Bohn et al., have been extensively studied, the genetic code
      has been identified for each of the PPs. The present study was carried out to
      clarify the mRNA expression and protein localization of PP11, PP12, PP19 at the
      cell level and also to define PP19 the nature of which has remained obscure. PP19
      was said to be placenta-derived S-100P. PP11 mRNA was not expressed in
      cytotrophoblast-derived normal placental tissue or endometrium-derived normal
      cells, but was expressed in syncytiotrophoblast-derived normal placental tissue,
      and in choriocarcinoma and endometrial adenocarcinoma, suggesting its involvement
      in carcinogenesis. PP12 mRNA was expressed in cytotrophoblast-derived normal
      placental tissue or endometrium-derived normal cells, but was not expressed in
      syncytiotrophoblast-derived normal placental tissue, choriocarcinoma or
      endometrial adenocarcinoma, suggesting that this protein serves in the function
      of normal cells. PP19 mRNA was expressed in the squamous epithelial cells of the
      uterine cervix and the villous cells, PP19 was localized in more differentiated
      regions, where cells tended toward keratinization, in both normal and dysplastic
      uterine cervices. In squamous cell carcinoma, PP19 was localized in more
      differentiated cells with a large cytoplasm. PP19 mRNA was not expressed in
      normal endometrial glands, but was detected in endometrial adenocarcinoma,
      suggesting its involvement in cell differentiation in cervical epitherial cells.

PMID- 8543851
TI  - [Usefulness of Doppler ultrasound in predicting the effect of gonadotropin
      releasing hormone agonist (GnRHa) on myoma uteri].
AB  - This paper shows the value of Doppler ultrasound of the uterine blood flow in
      predicting the effect of GnRHa on myoma uteri. Thirty-eight patients with myoma
      uteri were divided into two groups by Doppler ultrasound before treatment: a
      group with positive arterial blood flow in or around the myoma nodule, and
      another group with negative arterial blood flow. Histological examinations which
      were performed in thirty patients demonstrated that the myoma in the negative
      blood flow group showed higher hyalinization with poor vascularization. In
      fifteen patients treated with GnRHa (Buserelin 900 micrograms/day), a significant
      increase (p < 0.01) in the resistance index of the uterine arteries was induced
      and suppressed the serum estradiol concentration in all cases during GnRHa
      therapy. The size of the myoma nodules also decreased in all 6 patients in the
      positive blood flow group, but in only 3 of the 9 patients in the negative blood
      flow group during GnRHa therapy. These results indicated that Doppler assessments
      of the arterial blood flow in myoma would be useful in predicting the effect of
      GnRHa on myoma uteri.

PMID- 8543852
TI  - [The significance of invasion and vessel permeation in squamous cell carcinoma of
      the uterine cervix with invasion to a depth of 3 mm or less].
AB  - Nine-five patients with squamous cell carcinoma of the cervix invading to a depth
      of 3 mm or less (microinvasive carcinoma) were retrospectively viewed in regard
      to the depth of stromal invasion, the width of horizontal spread, confluent
      invasion, vessel permeation and lymph node metastasis. The type of treatment and
      outcome were also evaluated. Confluent invasion was found in 6 patient (6%), and
      vessel permeation in 9 patients (9%). Lymph node dissections were performed on 85
      patients, but no lymph node metastasis was found, irrespective of the presence of
      confluent invasion or vessel permeation. Fifty-five patients with no vessel
      permeation were treated by conization or total or modified racial hysterectomy,
      and none had a recurrence of the disease. Our results suggest that the presence
      of confluent invasion or vessel permeation does not influence the incidence of
      lymph node metastasis, but data in the literature indicate that confluent
      invasion and vessel permeation are risk factors for lymph node metastasis and
      invasive recurrence of the disease. We conclude that patients with invasion of
      depth 3m or less, with no confluent invasion and no vessel permeation, can be
      treated by conservative operation.

PMID- 8543853
TI  - [Annexin V in human platelets and its physiological role].

PMID- 8543854
TI  - [Intralymphatic administration of estramustine phosphate].

PMID- 8543855
TI  - [A case of endometriosis with repeated hemothorax at menstruation and
      retroperitoneal hematoma].

PMID- 8543856
TI  - [Laparoscopic operation of adnexal tumors].

PMID- 8543857
TI  - [New operative procedure for genital prolapse--partial colpocleisis with
      extensive suture of levatores].

PMID- 8543858
TI  - Flexor tendon-pulley interaction after tendon repair. A biomechanical study.
AB  - Ten normal ring fingers from ten donors were used to determine the effect of
      flexor tendon repair on the gliding resistance between the tendon and the A2
      pulley. Gliding resistance was measured for the intact FDP tendon and for the
      same tendon after it was cut transversely and repaired with a 4/0 Ticron core
      suture and a 6/0 running epitendinous nylon suture. After repair, the gliding
      pattern of the tendon through the A2 pulley changed significantly. The resistance
      and the friction coefficient were approximately doubled (P < 0.005).

PMID- 8543859
TI  - A new type of flexor tendon repair. Biomechanical evaluation by cyclic loading,
      ultimate strength and assessment of pulley friction in vitro.
AB  - Experiments were performed to evaluate biomechanical aspects of the performance
      of a "deep-biting peripheral suture" for flexor tendon repair, either when used
      alone or with a square or modified Kessler core stitch, and the technique was
      compared to the Kleinert repair. Tests included progressively increasing cyclic
      loads, force to pull the repair into the A2 pulley, and ultimate failure
      strength. 50% of the Kleinert repairs failed under 30 N cyclic loading, while
      100% of the DBPS plus Kessler core stitch repairs survived. There was no
      discernable difference in gliding function or repair bulk between these sutures,
      but ultimate strength increased significantly with the DBPS repairs. We concluded
      that the DBPS plus Kessler-type core stitch will survive active mobilization
      better than the Kleinert method.

PMID- 8543860
TI  - Functional results of dynamic splinting after transmetacarpal, wrist, and distal
      forearm replantation.
AB  - The results of replantation at the wrist and distal forearm are reported to be
      better than at the metacarpal level, in part because the latter involve direct
      injury to the intrinsic muscles. This study evaluates a new post-operative
      protocol for replantation at the metacarpal, wrist and distal forearm levels. 3
      days after replantation, the patient was placed in a dynamic crane outrigger
      splint with MP joint control, compensating for intrinsic muscle function loss.
      From 4 to 12 weeks, an anticlaw splint alternated with the outrigger splint.
      After 12 weeks, a dynamic wrist extension orthosis was added to the anti-claw
      splint. 11 patients (four replantations at the transmetacarpal level, three at
      the wrist and four in the distal forearm) had this protocol between 1988 and
      1993. For distal forearm replantation, TAM of fingers averaged 216 degrees, grip
      strength 42 lb, and pinch strength 7.2 lb with 75% good or excellent results. For
      wrist replantations, TAM of fingers averaged 243 degrees, grip strength 37 lb and
      pinch strength 10.6 lb with 100% good or excellent results. For transmetacarpal
      replantations, TAM of fingers averaged 189 degrees, grip strength 37 lb and pinch
      strength 5.6 lb, with 75% good and excellent results. Early protected
      mobilization, as described here, preserves tendon gliding, muscle strength and
      excursion. Our results support this protocol for wrist and distal forearm
      replantation and especially for transmetacarpal replantation, the results of
      which tend to be poor according to the medical literature.

PMID- 8543861
TI  - Reconstruction of a complex defect of the dorsum of the hand.
AB  - A 37-year-old right-handed male truck driver was admitted with a severe injury of
      the dorsum of his right hand following a traffic accident. He had a large
      combined defect involving skin, tendons and bone. A complex reconstruction was
      performed using a large iliac crest allograft, a tendon graft and a free serratus
      anterior flap in one stage, 8 hours after the injury. A skin graft was performed
      later. 2 years later the functional and aesthetic result are good.

PMID- 8543862
TI  - Correction of dorsi-flexed intercalated segment instability after restoration of
      scaphoid height in a cadaver model of scaphoid non-union.
AB  - Models of scaphoid non-union with static dorsi-flexed intercalated segment
      instability were produced in five frozen arms from cadavers or subjects following
      accidents by repetitive mechanical loading of the wrist joints longitudinally
      after a bone defect has been made at the mid-portion of the scaphoid. We designed
      four models of reduction: anatomical reduction; reduction with a shortened
      scaphoid; anatomical reduction but with the radio-lunate ligament sectioned, and
      a shortened scaphoid with the radio-lunate ligament sectioned. Results suggested
      that anatomical reduction with rigid fixation with a Herbert screw was most
      effective for correction of malalignment with DISI. Preservation of the radio
      lunate ligament during the palmar approach to the scaphoid seemed to be important
      to prevent ligamentous carpal instability.

PMID- 8543863
TI  - Pre-operative progressive distraction in old transcapho-peri-lunate dislocations.
AB  - Three cases of 6- to 8-week-old transcapho-peri-lunate dislocation of the carpus
      were treated with pre-operative progressive distraction, using an external
      fixation apparatus for 1 week. Surgical reduction and osteosynthesis of the
      scaphoid was then easily performed.

PMID- 8543864
TI  - Isolated dislocation of all five carpometacarpal joints.
AB  - Fracture-dislocation of all five carpometacarpal joints is extremely rare, only
      ten cases having been reported since 1873. A case of isolated dislocation of all
      five carpometacarpal joints is presented. A good result was obtained 1 year after
      open reduction and internal fixation. This case is the only isolated dislocation
      of all five carpometacarpal joints in the English literature.

PMID- 8543865
TI  - A cadaver study of the effects of dorsal angulation and shortening of the
      metacarpal shaft on the extension and flexion force ratios of the index and
      little fingers.
AB  - Two experiments were performed on the second and fifth metacarpals of five normal
      cadaver hands. The forces obtained on full extension and flexion of the digits
      were measured. An oblique osteotomy was performed on the shaft of the metacarpal
      and fixed with dorsal angulation. The forces obtained on extension and flexion of
      the digits were measured. The relationships between the changes in force and the
      angle were analyzed. Flexion force decreased and extension force increased as the
      dorsal angulation increased, and these were significant beyond 30 degrees of
      dorsal angulation. The differences between index and little fingers were not
      significant. In the second experiment, the metacarpal bone was shortened at the
      osteotomy site, and the same measurements made. Flexion and extension forces both
      decreased, and were significant beyond 3 mm of shortening. The differences
      between index and little fingers were not significant.

PMID- 8543866
TI  - Occult distal radial fractures.
AB  - The radiological diagnosis of distal radial fractures is usually easy, but some
      fractures without displacement cannot be detected at the first examination. In
      this retrospective study of 626 wrist injuries diagnosed as "wrist sprain" we
      found 39 distal radial fractures which were discovered only after repeated
      examinations. The incidence of distal radial fractures was much higher than other
      wrist fractures that were diagnosed after repeated examinations. Repeat standard
      four-view X-ray examination, as well as other imaging methods, are necessary to
      diagnose these fractures.

PMID- 8543867
TI  - Treatment of pseudarthrosis of the distal phalanx with a compression screw.

PMID- 8543868
TI  - Elbow fractures with carpal injuries.
AB  - We report four cases with six episodes of concurrent carpal and elbow fractures
      or dislocations. Few such combinations of injuries have been reported in the
      literature. We discuss the mechanism and management of such injuries and conclude
      that elbow injuries should be suspected in severe carpal injuries. Surgical
      treatment may be required in their management.

PMID- 8543869
TI  - A biomechanical study of the ulnar nerve at the elbow.
AB  - The relative elongation with elbow flexion of the ulnar nerve, proximal and
      distal to the cubital tunnel, and of the cubital tunnel retinaculum, was measured
      in cadaver specimens by stereophotogrammetry. The proximal part of the ulnar
      nerve elongated significantly with full elbow flexion. No significant change of
      length was measured in the distal part of the nerve. The length of the cubital
      tunnel retinaculum increased by an average of 45% from full elbow extension to
      full flexion.

PMID- 8543870
TI  - Outcome study of ulnar nerve compression at the elbow treated with simple
      decompression and an early programme of physical therapy.
AB  - Cubital tunnel syndrome is the second most common entrapment neuropathy of the
      upper limb. This paper presents the experience of treating cubital tunnel
      syndrome with simple decompression in 131 patients (164 ulnar nerves) over the
      past 12 years. 85% of these patients had mild or moderate ulnar nerve disease. In
      146/164 ulnar nerves (89%), simple decompression resulted in good or excellent
      immediate post-operative relief of symptoms. After an average follow-up of 4.3
      years (range, 0.8-12.0 years), 130/164 (79%) still reported good or excellent
      relief. The independent predictors of a better long-term outcome were absence of
      post-operative subluxation, greater body weight, normal pre-operative two-point
      discrimination (2-PD), and a more recent date of operation. A physical therapy
      rehabilitation program generally began on the day after surgery. Active
      participation in this predicted a rapid return to work or activities of daily
      living. The average time to return to work with simple decompression was 20
      workdays.

PMID- 8543871
TI  - Transposition of the ulnar nerve and its vascular bundle for the entrapment
      syndrome at the elbow.
AB  - Surgical findings show important alterations of the extrinsic and intrinsic
      vascularity of the ulnar nerve in the epitroclear groove. Current procedures are
      only able to solve the mechanical aspect of nerve compression. Transposition may
      cause additional iatrogenic ischaemic damage of endoneural vascularity if the
      nerve is separated from the ulnar collateral artery to achieve anterior
      mobilization. Our technique of transposition of the ulnar nerve with its vascular
      bundle maintains the advantages of anterior transposition currently in use, but
      is able to preserve the whole vascularity of the nerve, thus solving the
      biological aspect of nerve compression. This allows quicker recovery of axonal
      activity that was chronically compromised by the entrapment neuropathy. The
      technique and the results in 30 patients (90% excellent and good, 10% fair)
      treated since 1987 are presented.

PMID- 8543872
TI  - Intraneural ganglion of the posterior interosseous nerve with lateral elbow pain.
AB  - We report an intraneural ganglion of the posterior interosseous nerve causing
      lateral elbow pain. The cystic lesion was identified by magnetic resonance
      imaging, and surgical exploration using the microscope permitted complete
      extirpation of the cyst without damage to nerve tissue. The patient experienced
      complete relief from pain, with full preservation of function.

PMID- 8543873
TI  - Acute posterior interosseous nerve palsy caused by a synovial haemangioma of the
      elbow joint.
AB  - A case is described of spontaneous posterior interosseous nerve palsy of acute
      onset. The initial symptoms made it difficult to distinguish the condition from
      tendon rupture. The diagnosis was established using ultrasound, nerve conduction
      studies and MRI. The patient underwent surgery to decompress the posterior
      interosseous nerve and the histological examination identified the tumour as a
      synovial haemangioma. 12 months after the operation, the patient had made a
      complete recovery, confirmed by EMG.

PMID- 8543874
TI  - Delayed posterior interosseous nerve palsy.
AB  - A rare case of delayed posterior interosseous nerve palsy that developed 39 years
      after an unreduced anterior dislocation of the radial head is reported. The
      posterior interosseous nerve was compressed and narrowed at the arcade of Frohse.
      Radial head resection and release of the arcade was done. The paralysis continued
      to recover 6 weeks after operation. The nerve, at the arcade of Frohse, was
      susceptible to compression by the dislocated radial head, especially in the
      supinated position. Repeated supination and pronation movement over time may have
      led to developmental changes that caused the delayed nerve palsy.

PMID- 8543875
TI  - Early results of conventional versus two-portal endoscopic carpal tunnel release.
      A prospective study.
AB  - The authors compare in a prospective, randomized study the early outcome of
      carpal tunnel release using either a conventional palmar open release (n = 40) or
      a two-portal endoscopic release (n = 56). Both groups were similar. No
      statistically significant differences were found regarding pain, disappearing of
      paraesthesiae or time to return to work. However, better recovery of grip
      strength was observed in the endoscopic group at 1 and 3 months. No surgical
      complications were observed in either group.

PMID- 8543876
TI  - A comparison of immediate and delayed nerve repair using autologous freeze-thawed
      muscle grafts in a large animal model. The simple injury.
AB  - Freeze-thawed muscle grafts (FTMG) have been suggested as an alternative to nerve
      grafts in reconstruction of peripheral nerve defects. This study compares the
      results of immediate and delayed nerve repair with freeze-thawed muscle graft in
      a large animal model. Under general anaesthesia, ten adult sheep underwent
      excision of 3 cm of the right median nerve. Five had immediate nerve
      reconstruction with FTMGs (Group A) and five were repaired after 4 weeks (Group
      B). At 6 months, both the right (repaired) and left ("control") median nerves of
      each sheep were assessed. Nerve blood flow distal to the graft in both groups of
      repaired nerves was approximately 60% of that in their respective control nerves.
      Peak nerve conduction velocities were significantly slower in the repaired
      nerves. The mean fibre diameters of the immediate and delayed repairs were 5.06
      and 3.90 mu respectively compared to a control mean of 8.58 mu. G-ratios
      confirmed that the repaired nerves in both groups were well myelinated. The
      authors conclude that the FTMG can be used in delayed as well as immediate nerve
      reconstruction with minimal impairment of final results.

PMID- 8543877
TI  - Tenodesis of extensor digitorum in treatment of brachial plexus injuries
      involving C5, 6, 7 and 8 nerve roots.
AB  - Restoration of motor function in the hand is difficult in brachial plexus
      injuries in which the C5, 6, 7 and 8 roots are involved, because there are
      insufficient motors available for transfer to restore the extensors of the
      fingers and wrist. We have used extensor digitorum tenodesis in 11 cases and
      found it effective and simple.

PMID- 8543878
TI  - The effect of unilateral intercostal nerve transfer upon lung function.
AB  - Intercostal nerve transfer is a well-established technique in the treatment of
      some severe brachial plexus lesions in adults. There is, however, concern that in
      the presence of an ipsilateral phrenic nerve palsy it may lead to a significant
      compromise of respiratory function. 20 patients having intercostal nerve
      transfers had their lung function assessed pre-operatively and 6 weeks post
      operatively. The patients were subsequently questioned about symptoms of
      respiratory dysfunction. There was no evidence that intercostal nerve transfer
      leads to a significant reduction in respiratory function in adults. It therefore
      appears safe to perform intercostal nerve transfers in adults following brachial
      plexus injuries even in the presence of an ipsilateral phrenic nerve palsy.

PMID- 8543879
TI  - The practical use of axillary brachial plexus block for hand surgery.
AB  - A retrospective study of 178 patients undergoing axillary brachial plexus block
      (ABPB) for hand surgery used information gathered by a computer-aided anaesthetic
      record keeping system. The practical use of local techniques to augment the block
      meant that only two of the 178 patients required a general anaesthetic, giving a
      success rate of 98.8%. There were no significant complications.

PMID- 8543880
TI  - The use of Bier's block for day case surgery.
AB  - With the increasing popularity of day case surgery it is important to ensure that
      safe and appropriate techniques are being used. We retrospectively reviewed a
      large series of 732 patients who underwent planned day case hand surgery under
      intravenous regional anaesthesia (modified Bier's block) over a 5-year period. We
      found a modified Bier's block to be ideally suited to day case surgery with no
      deaths, minimal morbidity and a success rate in excess of 98%.

PMID- 8543881
TI  - Hand surgery coding and classification.
AB  - The development of codes for hand surgery as part of the Read Code System is
      described. A lexicon of clinical terms and surgery has been developed, and will
      shortly be available from the National Health Service Centre for Coding and
      Classification in Loughborough, UK.

PMID- 8543883
TI  - A method of two-dimensional measurement for evaluating finger motion impairment.
      A description of the method and comparison with angular measurement.
AB  - A new method has been designed for direct measurement of the two-dimensional
      range of motion (ROM) of the finger. The two-dimensional method encompasses the
      postures imposed by various combinations of contraction and relaxation of the
      finger motors, so that an individual muscle injury or adhesion might be more
      easily detected. The figures and values obtained from the two-dimensional method
      are easier to interpret than those from conventional measurements, making the
      progress of the rehabilitated finger more apparent. Since the passive ROM cannot
      be evaluated by this method, it is a supplement rather than a substitution for
      the conventional range of motion evaluation for each joint. The drawback of the
      two-dimensional method is that it is more difficult to use than the conventional
      method.

PMID- 8543882
TI  - Post-operative infection following hand surgery. Guidelines for antibiotic use.
AB  - An audit was designed to analyse the risk factors for developing post-operative
      wound infection following hand surgery. 249 consecutive patients were
      prospectively entered into the study. 236 (95%) patients were available for
      follow-up. Infection was diagnosed by clinical criteria. There was an infection
      rate of 10.7% in elective operations and 9.7% in emergency operations. There was
      no significant reduction in infection rate in the elective group with the use of
      antibiotics (P = 0.5). In the emergency group of patients peri-operative
      antibiotic administration was associated with an 8.5-fold reduction in infection
      rate (P = 0.014). The presence of a dirty wound was associated with a 13.4-fold
      increase in post-operative wound infection rate (P = 0.002). A postal
      questionnaire of members of the British Society for Surgery of the Hand revealed
      a wide variation in antibiotic usage. Guidelines for antibiotic use in patients
      undergoing hand surgery are presented.

PMID- 8543884
TI  - Quantitative analysis of the linkage between the interphalangeal joints of the
      index finger. An in vivo study.
AB  - We have established a simple method of measuring joint motion under physiological
      conditions. For this purpose we use an ultrasound measuring system employing
      marker points consisting of miniaturized ultrasound transmitters. This device was
      tested on a simple biomechanical model, the linkage of the proximal and distal
      interphalangeal joints. The angles of these joints were recorded during opening
      and closing of the fist in 34 index fingers of 17 healthy persons. The results of
      the measurements were plotted on a rectangular coordinate system. Analysis showed
      an approximately linear linkage between the IP joints of the index finger. The
      curve for extension was the same as that for flexion. The linkage varies greatly.
      On average 1 degree of PIP joint flexion is equivalent to 0.76 degree of DIP
      joint flexion. Our study showed no significant difference between the dominant
      and non-dominant hand. The results showed that there is a linear linkage between
      the proximal and distal interphalangeal joints, which is equal for flexion and
      extension.

PMID- 8543885
TI  - Partial trapeziectomy and interpositional arthroplasty for trapeziometacarpal
      osteoarthritis of the thumb.
AB  - Partial excision including the articular surface of the trapezium and
      interpositional arthroplasty using one half of the flexor carpi radialis tendon
      was done in 36 hands. The joint capsule was reattached to the trapezium and the
      thumb immobilized for 4 weeks post-operatively. No ligament reconstruction was
      done. 30 hands (83.6%) had complete relief of pain. The average post-operative
      pinch strength was 11 lb. Three patients who complained of weakness of pinch had
      hyperextension of the MP joint. Correction of MP hyperextension is recommended to
      improve pinch strength. The outcome of this operation is comparable to any of the
      techniques described in the literature. The technique is simple and easy to
      perform. Since the capsule is closed the operation is truly an interpositional
      arthroplasty.

PMID- 8543886
TI  - Resection arthroplasty of the metacarpophalangeal joints in rheumatoid arthritis.
      Results after more than 15 years.
AB  - In a retrospective study of resection arthroplasty of the MP joints in rheumatoid
      arthritis, 23 patients (32 hands, 128 joints) have been followed for 15 to 22
      years. Patient satisfaction was high, and all patients had significant pain
      relief. Active motion of the joints averaged 35 degrees, ranging from full
      extension to 35 degrees of flexion. Ankyloses developed in five hands (13 joints,
      10%). Ulnar deviation of more than 15 degrees occurred in six patients (ten
      hands, 30%). Over the course of several years a significant remodelling of the
      joints was to be observed. In six hands (19%) the metacarpal heads became
      spontaneously restored to ball-shaped geometry. Gross metacarpal resorption was
      observed in nine hands (30%), causing significant shortening of the metacarpals.
      In one-third of patients the final result was rated as good, fair and poor,
      respectively. Careful patient selection is mandatory. Patients with mutilating
      arthritis should be excluded from the procedure; rheumatoid destruction of the
      wrist joint definitely influences the final result.

PMID- 8543887
TI  - Articular pigmented villonodular synovitis of the MP joint of the hand.

PMID- 8543888
TI  - ECG of the month. Crazy rhythm. Multifocal atrial tachycardia.

PMID- 8543889
TI  - Temporal bone fractures.
AB  - Temporal bone fractures are clinically interesting because of the rich anatomy
      across which they traverse. These fractures most often present after blunt head
      trauma and may present with a variety of symptoms including facial nerve
      paralysis, hearing loss, and vertigo. This paper will classify these fractures
      and discuss their associated clinical findings.

PMID- 8543890
TI  - Physicians, smoking and hospitals. Committee on Chronic Diseases.
AB  - Physicians today can make a significant impact on the nation's health through
      preventive measures. The greatest potential lies in the modification of peoples'
      smoking habits. Physicians should be taught specific smoking intervention skills,
      act as role models, and carry their examples into all hospital settings and their
      private lives.

PMID- 8543891
TI  - Pituitary tumor and low gonadotropins in a patient with Turner's syndrome.
AB  - Despite years of prolonged hypersecretion of gonadotropins, patients with
      Turner's syndrome rarely develop nonfunctional pituitary tumors. We present here
      the case of an 18-year-old woman who had both Turner's syndrome and a pituitary
      tumor. The patient was diagnosed at age 16 with Turner's syndrome, after
      presenting with primary amenorrhea. She was subsequently found to have
      inappropriately low levels of luteinizing hormone and follicle-stimulating
      hormone. Workup confirmed the unique combination of Turner's syndrome, a
      pituitary tumor, low gonadotropins and high androgen levels.

PMID- 8543892
TI  - Heat exposure in an enclosed automobile.
AB  - During July 1995, an infant in southeast Louisiana died as a result of heat
      exposure in an enclosed automobile. To evaluate degree of heat exposure in a
      vehicle, we compared the temperature rise inside an enclosed, dark-colored
      vehicle with the temperature rise in light-colored vehicle with the windows
      partly open. Within 20 minutes, readings in both cars exceeded 125 degrees F and
      reached approximately 140 degrees F in 40 minutes--a temperature rise of over 45
      degrees F. A person who is unable to remove himself from an enclosed vehicle is
      at risk for a life-threatening crisis if left alone in a sun-exposed car for even
      a relatively short period of time.

PMID- 8543893
TI  - Adjunct fibula strut bone graft in resurfacing hip arthroplasty.
AB  - Femoral neck fracture following surface replacement is a reported complication.
      Adjunct autogenous fibula strut bone grafting has been proposed as a means of
      reducing or eliminating this occurrence. This paper reports the long-term follow
      up of two cases. One patient did well for 9 years prior to sustaining a traumatic
      femoral neck fracture while intoxicated; the second patient continues to do well
      8.5 years postoperatively. While definite conclusions cannot be drawn, these two
      patients represent our longest-clinical successes using surface replacement
      arthroplasty.

PMID- 8543894
TI  - Ruptured splenic aneurysm: case report in a young adult.
AB  - The purpose of this paper is to point out that although the incidence of ruptured
      splenic artery aneurysm is a rare occurrence, it should be considered in the
      differential diagnosis of acute abdominal pain. The case reported is a 21-year
      old white woman who presented with acute abdominal pain for 24 hours. While being
      evaluated in the emergency room, her splenic artery aneurysm ruptured. The
      diagnosis was made by use of ultrasound, computerized tomography, and exploratory
      surgery. In spite of a critical and life-threatening episode, the patient
      survived. Even though there is disagreement about the necessity for surgical
      intervention for asymptomatic aneurysms, this case reinforces the recommendation
      for surgical excision.

PMID- 8543895
TI  - [Manual fragmentation of deep vein thrombosis].
AB  - To preserve the venous function after deep vein thrombosis, physical treatment
      combines elastic stockings, active exercises, lower limbs elevation, ventilatory
      exercises and manual lymph drainage. When this traditional treatment is not
      sufficient, we use a new technique. It aims at fragmenting thrombus by
      compressing it between the physiotherapist's fingers and the patient's bone. In
      order to define the fragmentation sites we use the Triplex ultrasonography. This
      technique has been tested on ten patients with serious thrombosis, whom the
      thromboembolic risk was first controlled. The evaluation was performed by the
      clinical examination, echography and occlusive impedance plethysmography
      rheography. The improvement of the subjective and objective signs leads to use
      our technique. It has to be validated on a larger scale to extend its use.

PMID- 8543896
TI  - [Late complications of abdominal aortic prostheses: false aneurysms and aorta
      digestive fistulas].
AB  - Pseudoaneurysms of the abdominal aorta (PAAA) are late complications of aortic
      reconstruction that occur with an incidence varying from 4.8 to 6.3% associated
      with an operative mortality of 21 to 35%. Between 1987 and 1994, 16 patients with
      a PAAA (14 men and two women, with a mean age of 69.5 years, ranging from 55 to
      82 years) were treated in our unit. An anastomotic rupture with a pseudoaneurysm
      diameter varying from 50 to 75 mm was present in five cases (group 1). The eleven
      other cases were aorto-enteric fistula, isolated in six cases (group 2) and
      associated with local and/or general sepsis signs in five cases (group 3). The
      mean interval from the time of the primary aortic graft, which was performed as
      treatment for aortic aneurysm in six cases and for aortoiliac occlusive disease
      in 10 cases, and the diagnosis of the PAAA, was 11.3 years. An in situ
      replacement of the aortic graft with an interposition of the greater omentum was
      performed in each patient of groups 1 and 2, associated with an enteric
      restoration in the latter. Group 3 patients were treated by removal of the
      infected graft with closure of the aortic stump and extra-anatomic bypass. During
      the post-operative period, five deaths (31%) and one limb amputation (6%)
      occurred, i.e. one death in group 1 (20%), one in group 2 (17%) and three in
      group 3 (60%) associated with a limb amputation (20%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8543897
TI  - [Local complications of arterial catheterization by the Scarpa technique. New
      therapeutic approaches].
AB  - Local complications of femoral artery catheterization are less frequent than
      those occurring after puncture of other sites. Nevertheless, their prevalence is
      estimated to be 0.5 to 1%. Some of them are health-threatening. Fifty-one
      arterial obstructions, 18 hematomas, 38 pseudoaneurysms and 11 arteriovenous
      fistulas have been operated on during a 25 years period. They were responsible
      for 4 death and 1 above-knee amputation. During the same period, several
      arteriovenous fistulas and pseudoaneurysms were treated conservatively. Our study
      and the literature show that Duplex-scan allow a management of these
      complications more eclectic than previously. Arterial obstructions should be
      operated on rapidly in case of acute ischemia with neurologic deficit. When the
      ischemia is less severe, heparin therapy may help the lysis of the clot. If not,
      simple thrombectomy is sufficient when the arteries are normal while more
      complete revascularizations after angiographic evaluations are necessary in case
      of atherosclerotic arteries. Hematomas should be avoided by local compression
      during a period which should be longer when the hole is large or when
      anticoagulation is used. An implantable bio-absorbable device has been used with
      good results in another study. Increasing hematomas and hematomas responsible for
      neurologic symptoms should be operated on. Blood restoration should be rigorous
      in patients with cardiac disease. Pseudoaneurysms may be easily diagnosed and
      controlled with Duplex-scan. Ultrasound-guided compression during 10 to 20
      minutes periods should be used before deciding surgical repair.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8543898
TI  - [Magnetic resonance imaging and cerebral ischemia].

PMID- 8543899
TI  - [Results of magnetic resonance imaging in the acute phase of cerebral
      infarction].
AB  - Brain ischemia is now possible to trace through the multiple facets of MRI,
      morphological as well as functional. Experimental studies have been conducted for
      many years and clinical feasibility is reached. Although the initial decrease in
      blood flow does not influence morphological imaging, this early phase is shown
      with functional MRI, either with diffusion imaging or with cerebral blood volume
      imaging. The later is achieved either with the calculation of the integral of the
      first passage of a bolus of a diffusible paramagnetic agent or with the
      circulation of positive or negative blood pool contrast agents. This may serve to
      confirm an early diagnosis before inclusion in therapeutic trials. Immediate
      metabolic changes are reflected on phosphorus and proton spectroscopy achievable
      during the same session as imaging. This type of information may at this stage
      serve as a reference. It allows observation of the turnover of lactate over time
      in the lesion and the neuronal loss shown by decreased N-acetyl-aspartate. Edema,
      as a reaction to ischemia, builds up over time and has already been described for
      long as it modifies T1- and T2- weighted sequences. Similarly the breakdown of
      the blood-brain barrier is well known on conventional sequences because it
      produces contrast enhancement.

PMID- 8543900
TI  - [Role of magnetic resonance imaging in cerebral venous thrombosis].
AB  - Magnetic resonance imaging is at present the method of choice for the diagnosis
      and follow up of cerebral venous thrombosis. It allows both the visualisation of
      the thrombus itself, mostly as an increased signal in T1 and T2 images, and its
      potential recanalisation. It also detects the associated parenchymal lesion:
      isolated mass effect, edema, or hemorrhage. If necessary, it can be coupled with
      magnetic resonance angiography, thus allowing in the majority of cases, to avoid
      intra arterial angiography.

PMID- 8543901
TI  - [Magnetic resonance imaging in vascular dementia].
AB  - The heterogeneity of vascular dementia depends on the cause, size, location and
      nature of the vascular lesions (36, 62). Magnetic resonance imaging (MRI)
      techniques are of major interest to detect the vascular origin of dementia: the
      lack of focal lesions or leukoencephalopathy excludes the vascular origin of
      dementia (36). Occlusions of large extra-cerebral arteries usually lead to
      cortical or large subcortical infarcts or both (28). Dementia may be due to
      multiple infarcts or to a single infarct located in a strategic area (47).
      Lacunar infarcts are due to the occlusion of one single deep perforator with a
      thickening of the arterial wall due to lipohyalinosis (25), usually in a patient
      with arterial hypertension; lacunes are located in a territory supplied by the
      deep perforators. They appear as hyperintense in T2-weighted sequences and hypo
      intense in T1-weighted sequences. Old small hemorrhages have the same appearance
      than infarcts on CT-scans but their center appears hypo-intense in T2-weighted
      sequences. In normal subjects, age and arterial hypertension are risk factors for
      hemispheric white matter hyperintensities (59, 60). Their vascular origin is
      likely because of the evidence of lesions of the wall of deep perforators (17,
      21), their association with lacunes (17, 21, 30, 37) or deep hemorrhages (30, 32,
      37), and their frequency in amyloid angiopathy (26). Their prevalence is higher
      in vascular dementia than in Alzheimer's disease (59). They sometimes fulfill
      criteria for Binswanger's disease (5). Even after exclusion of predisposing
      factors they remain frequent in healthy subjects over 50 years (39, 56); however,
      whether they herald subsequent dementia remains unsettled.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8543902
TI  - [Diffusion, perfusion and functional magnetic resonance imaging].
AB  - Recent developments in the use of Magnetic Resonance Imaging (MRI) to measure and
      image molecular diffusion and blood microcirculation (perfusion) hold significant
      promise in the noninvasive evaluation of normal brain function and functional
      disorders. Molecular diffusion is the result of spontaneous random motion that
      involves all molecules and probes molecular motion at microscopic level. Using
      diffusion MRI, information on tissue geometry and compartmentation effects can be
      obtained. Diffusion MRI has been used to map myelin fiber orientation in brain
      with high accuracy. Diffusion MRI is also the only imaging modality which shows
      brain ischemia at a very early stage, even before T1w or T2w MR images become
      abnormal, offering great promises in the management of stroke patients. Also,
      diffusion imaging may be used to monitor tissue temperature changes noninvasively
      during hyperthermia or laser surgery. On the other hand, MRI can provide
      information on tissue perfusion. Several methods have been proposed, some of them
      including tracers or contrast agents. The most successful approach for brain
      function studies, however, is based on the sensitivity of MRI to magnetic effects
      induced by changes in the oxygenation status of hemoglobin (deoxyhemoglobin).
      These effects have already been used to characterize hematomas. These effects may
      also be exploited to detect small modulation in red blood cell oxygen content
      related to local variations in blood flow and oxygen consumption in tissues. In
      the brain cortex, such variations may be induced by external stimuli or internal
      cognitive processes. Capillary blood deoxyhemoglobin thus acts as a natural
      endogeneous contrast agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8543903
TI  - [Leg ulcer and Klinefelter syndrome].
AB  - We report a case of 47 years old patient who was admitted to hospital because of
      bilateral leg ulcers for 6 years. Chromosome analysis revealed XXY karyotype,
      confirming the clinical diagnosis of Klinefelter's syndrome. Testosterone level
      was low and Plasminogen Activator Inhibitor (PAI-1) was elevated. The patient was
      given androgen therapy which resulted in a normalization of the PAI-1 activity.
      The frequency of leg ulcers in patients with Klinefelter syndrome is between 6
      and 12% according to studies. Different causes would explain the tendency towards
      leg ulcers in Klinefelter's syndrome: conjunctive tissues abnormalities were
      revealed in some studies. A higher frequency of venous insufficiency is reported
      in patients with Klinefelter's syndrome, either due to the particular morphology
      (obesity, taller size) or due to an androgen deficiency. A few arterial
      dysplasias cases of arteries's legs were described in patients with leg ulcers
      and Klinefelter syndrome. Haemostasis disorders presented in this case and
      normalized after androgen therapy will contribute to the physiopathologic
      discussion.

PMID- 8543905
TI  - [Right aortic arch and "isolated" left brachiocephalic arterial trunk. Fortuitous
      discovery in angiologic practice].
AB  - An exceptional case of congenital malformation of the supra-aortic trunks was
      discovered fortuitously during an angiographic examination. The echo-Doppler and
      arteriography findings are reported together with an outline of the most frequent
      congenital malformations of the supra-aortic trunks.

PMID- 8543904
TI  - [Vascular complications of lumbar disk surgery. Report of two cases and review of
      the literature on 122 cases].
AB  - We report two cases of right lumbar common iliac arteriovenous injury after an
      operation on the L4-L5 disk. One case was an arteriovenous fistula disclosed 5
      years after the operation and in the other case, a postoperative acute
      haemorrhage. A retrospective study is carried out in the literature aiming at
      establishing the frequency of vascular injury in lumbar disk surgery, their
      nosologic definition, and the provided treatment. One hundred and twenty two
      observations were taken into account. The frequency cannot be determined. 78 of
      these observations (63.9%) reported an arteriovenous fistula between two elements
      of the aortic-cava intersection, with acute revelation (6.4%), sub-acute (19%) or
      late as a right cardiac failure (64%). Thirty one cases of acute haemorrhages
      through isolated arterial wound (25.4%), 3 cases of arterial or venous thrombosis
      (2.5%) and 10 cases of false aneurysms (8.2%) were found. The treatment was
      always surgical, sometimes in high emergency. In the case of haemorrhage the
      death rate was 21% and in the event of fistula 1.3%. Morbidity was 11.5%, mostly
      due to a post-phlebitic syndrome. These results reduce the mildness reputation of
      lumbar disk surgery all the more as recording of the complications is under
      estimated and most of them are found far from the initial act.

PMID- 8543906
TI  - [Chickenpox and limb ischemia. Report of a case].
AB  - We have observed in our department a subacute left inferior limb ischemia by a
      forty one years old man in the following of a chicken pox while big arteries
      (arteria profunda femoris, lateral plantar artery, arteria dorsalis pedis) were
      attacked. We have not noticed in the medical literature such a case described. We
      have treated this ischemia by an in situ fibrinolysis which lead to a total
      clinical recovery, a complete patency of the lateral plantar artery and the
      arteria dorsalis pedis, and an incomplete patency of the arteria profunda
      femoris. We expose a few physiopathological hypothesis. But, in any case, we have
      not the proof of a connection between ischemia and the viral infection.

PMID- 8543907
TI  - Placental corticotrophin-releasing hormone: there by accident or design?

PMID- 8543908
TI  - Endocrine peptides 'moonlighting' as immune modulators: roles for somatostatin
      and GH-releasing factor.

PMID- 8543909
TI  - 1,25-Dihydroxyvitamin D3-induced upregulation of the thyrotropin-releasing
      hormone receptor in clonal rat pituitary GH3 cells.
AB  - 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is active in primary dispersed and clonal
      pituitary cells where it stimulates pituitary hormone production and agonist
      induced hormone release. We have studied the effect of 1,25-(OH)2D3 on
      thyrotropin-releasing hormone (TRH) binding in clonal rat pituitary tumour (GH3)
      cells. Compared with vehicle-treated cells, 1,25-(OH)2D3 (10 nmol/l) increased
      specific [3H]MeTRH binding by 26% at 8 h, 38% at 16 h, 35% at 24 h and reached a
      maximum at 48 h (90%). In dose-response experiments, specific [3H]MeTRH binding
      increased with 1,25-(OH)2D3 concentration and reached a maximum at 10 nmol/l.
      Half-maximal binding occurred at 0.5 nmol 1,25-(OH)2D3/l. The vitamin D
      metabolite, 25-OH D3, increased [3H]MeTRH binding but was 1000-fold less potent
      than 1,25-(OH)2D3. In equilibrium binding assays, treatment with 10 nmol 1,25
      (OH)2D3/l for 48 h increased the maximum binding from 67.4 +/- 8.8 fmol/mg
      protein in vehicle-treated cells to 96.7 +/- 12.4 fmol/mg protein in treated
      cells. There was no difference in apparent Kd (1.08 +/- 0.10 nmol/l for 1,25
      (OH)2D3-treated and 0.97 +/- 0.11 nmol/l for vehicle-treated cells). Molecular
      investigations revealed that 10 nmol 1,25-(OH)2D3/l for 24 h caused an 8-fold
      increase in TRH receptor-specific mRNA. Actinomycin D (2 micrograms/ml, 6 h)
      abrogated the 1,25-(OH)2D3-induced increase in [3H]MeTRH binding. Cortisol also
      increased [3H]MeTRH binding but showed no additivity or synergism with 1,25
      (OH)2D3. TRH-stimulated prolactin release was not enhanced by 1,25-(OH)2D3. We
      conclude that the active vitamin D metabolite, 1,25-(OH)2D3, caused a time- and
      dose-dependent increase in [3H]MeTRH binding. The effect was vitamin D metabolite
      specific and resulted from an upregulation of the TRH receptor. Further studies
      are needed to determine the functional significance of this novel finding.

PMID- 8543910
TI  - Differential expression of 11 beta-hydroxysteroid dehydrogenase 1 and 2 in the
      developing ovine fetal liver and kidney.
AB  - In adult mammals, liver and kidney are the two major sites of biosynthesis for 11
      beta-hydroxysteroid dehydrogenase (11 beta-HSD) 1 and 2 respectively. In the
      present study, the expression of these two isozymes in the developing ovine fetal
      liver and kidney was characterized. Livers and kidneys were obtained from fetal
      sheep at days 85, 100-120 and 140-143 of gestation (term = 145 days). Tissue
      levels of 11 beta-HSD2 mRNA were assessed by Northern blot analysis. 11 beta-HSD
      dehydrogenase and reductase activities in tissue homogenates were determined by a
      radiometric conversion assay using cortisol and cortisone as physiological
      substrates respectively. The unidirectional 11 beta-HSD2 dehydrogenase activity
      was identified by its distinct cofactor preference (NAD), and by its unique
      ability to metabolize dexamethasone (Dex). In the liver, 11 beta-HSD1
      dehydrogenase and reductase activities were present by day 85, and their levels
      did not change between days 85 and 100-120 but increased more than twofold at
      days 140-143. This was consistent with changes we reported previously in the
      fetal hepatic 11 beta-HSD1 mRNA. 11 beta-HSD1 reductase activity was always
      higher than the dehydrogenase activity. 11 beta-HSD2 mRNA and activity were
      undetectable in the fetal liver at all three ages. By contrast, 11 beta-HSD2 mRNA
      was present in the fetal kidney by day 85, and its abundance increased
      progressively thereafter. There was a parallel increase in the renal 11 beta-HSD2
      activity. Dex was also converted to 11-dehydro-Dex by the fetal kidney. In
      keeping with the absence of the full-length 11 beta-HSD1 mRNA, 11 beta-HSD1
      activity was undetectable in the kidney. These results indicate that (1) 11 beta
      HSD1 and 2 genes are differentially expressed and regulated in the fetal liver
      and kidney during development, (2) since the hepatic 11 beta-HSD1 reductase
      activity is always higher than the dehydrogenase activity, the fetal liver may be
      a potential extra-adrenal source of cortisol, and (3) 11 beta-HSD2 in the kidney
      may play a very important role in protecting the fetus from elevated levels of
      bioactive glucocorticoids.

PMID- 8543911
TI  - Neural expression of the pituitary GH gene.
AB  - It is well established that GH-like proteins and mRNA are present in
      extrapituitary tissues, but it is not known whether this reflects ectopic
      transcription of the pituitary GH gene or the expression of a closely related
      gene. This possibility was, therefore, further investigated. Immunoreactive (IR)
      GH-like proteins were readily measured by RIA and immunoblotting in hypothalamic
      and extrahypothalamic brain tissues of the domestic fowl, in which GH-IR was
      similar in size and antigenicity to pituitary GH. RT-PCR of mRNA from these brain
      tissues, with oligonucleotide primers spanning the coding region of pituitary GH
      cDNA, also generated cDNA fragments identical in size (689 bp) to pituitary GH
      cDNA. The amplified brain cDNA sequences contained BamH1 and Rsa1 cleavage sites
      similar to those located in pituitary GH cDNA. These cDNA sequences also
      hybridized with a cDNA probe for chicken GH cDNA, producing moieties of expected
      size that were identical to the hybridizing moieties in pituitary tissue. The
      nucleotide sequences of the PCR products generated from hypothalamic and
      extrahypothalamic brain tissues, determined by a modified cycle dideoxy chain
      termination method, were also identical to pituitary GH cDNA. This homology
      extended over 594 bp of the hypothalamic cDNA fragment (spanning nucleotides 65
      to 659 of the pituitary GH cDNA and its coding region for amino acids 4 to 201)
      and 550 bp of the extrahypothalamic cDNA fragment (spanning nucleotides 76 to 626
      of pituitary GH cDNA and its coding region for amino acids 8 to 190). These
      results clearly establish that pituitary GH mRNA sequences are transcribed in
      hypothalamic and extrahypothalamic tissues of the chicken brain, in which GH-IR
      proteins are abundantly located. However, as GH mRNA could not be detected in the
      chicken brain by Northern blotting, its turnover may be more rapid than in
      pituitary tissue. The local production of GH within the brain nevertheless
      suggests that it has paracrine roles in modulating neural or neuroendocrine
      function.

PMID- 8543912
TI  - Inhibition of mouse placental lactogen-II release from placental cells by
      interleukin-1 after mid-pregnancy.
AB  - The effects of interleukin (IL)-1 and granulocyte-macrophage colony stimulating
      factor (GM-CSF), which are present in the mouse placenta, on the secretion of
      mouse placental lactogen (mPL)-1 and mPL-II by placental cells were tested in
      vitro. IL-1 alpha and IL-1 beta, 2.5 nmol/l each, significantly inhibited mPL-II
      secretion by cells from days 9 and 12 of pregnancy, but did not affect mPL-II
      secretion by cells from day 7 of pregnancy or mPL-I secretion by cells from days
      7, 9 or 12 of pregnancy. GM-CSF had no effect on mPL-I and mPL-II secretion by
      cells from days 7, 9 or 12 of pregnancy. The inhibitory effects of IL-1 alpha and
      IL-1 beta on mPL-II secretion were completely eliminated by the addition of
      antibodies to IL-1 alpha and IL-1 beta respectively. Western blot analysis for
      mPL-II indicated that IL-1 alpha significantly reduced the intensity of the mPL
      II band. Steady-state levels of mPL-II mRNA, assessed by Northern blot analysis,
      were reduced by incubation of placental cells from day 12 of pregnancy with 2.5
      nmol/l IL-1 alpha for 5 days. Co-incubation of 0.25 pmol/l IL-1 alpha, 25 pmol/l
      IL-6, and 25 pmol/l tumor necrosis factor-alpha, each of which did not
      significantly inhibit mPL-II secretion by itself, together inhibited mPL-II
      secretion. These results suggest that IL-1, but not GM-CSF, is a potent inhibitor
      of mPL-II secretion after mid-pregnancy, and that the combined action of
      cytokines can inhibit mPL-II secretion.

PMID- 8543913
TI  - Adrenalectomy induces a decrease in the light scatter properties and amylase
      content of isolated zymogen granules from rat pancreas as analyzed by flow
      cytometry.
AB  - The effect of glucocorticoid deprivation induced in male rats by adrenalectomy on
      the pancreatic zymogen granules was studied. Zymogen granules were purified from
      control, sham-operated and adrenalectomized animals studied 1, 3 and 7 days after
      surgery. The zymogen granules were characterized by flow cytometry, and in each
      granule the size (based on the forward or low angle light scatter (FSC)
      parameter), membrane complexity (based on side or 90 degrees light scatter (SSC)
      parameter) and amylase content were evaluated. Amylase content/DNA ratio in
      pancreatic homogenates was also analyzed. The zymogen granules of the control
      rats were found to be distributed in two populations: a major one-R1 (95.45 +/-
      1.21%)-containing zymogen granules with a smaller mean size and complexity, and a
      minor population-R2 (4.45 +/- 0.24%)-the granules of which had a mean size which
      was larger and more complex. At day +1 after adrenalectomy the zymogen granules
      were significantly (P < 0.05) smaller than those of control animals. The R2
      zymogen granules were similar to those from R1 as regards their size, but were
      more complex, suggesting that the immediate effect of glucocorticoid deprivation
      is to induce a depletion of the larger granules presumably belonging to the R2
      population. The amount of amylase per granule did not vary at day +1 after
      adrenalectomy, although the amylase content/size ratio per granule was
      significantly (P < 0.001) increased. This mechanism could be explained in terms
      of the existence of a bypass defined in the adrenalectomized animals between the
      granular content and cytosolic enzymes. Prolongation of the adrenalectomy period
      to 3 and 7 days resulted in a progressive increase in zymogen granule size and
      complexity, both parameters showing similar characteristics to those of the
      controls at day +7 after adrenalectomy. However, the percentage of zymogen
      granules within the R1 and R2 populations was clearly different from that of
      controls since the R2 population was much more numerous (11.25 +/- 0.75% and
      15.25 +/- 1.15% (adrenalectomized rats at days +3 and +7 respectively) versus
      4.45 +/- 0.24% (controls)). An increase in the content of amylase per DNA was
      observed in adrenalectomized rats at day +1 although this transient effect cannot
      be related to glucocorticoid deprivation because it was also observed in sham
      operated rats (day +1). However, a significant reduction, nearly 64%, in the
      amylase content/DNA ratio is produced by the absence of glucocorticoids 7 days
      after adrenalectomy and this is associated with a reduction in the content of
      amylase in each individual zymogen granule which reaches a minimum 3 days after
      adrenalectomy. It should be noted that, despite this, the enzyme concentration in
      each granule remains constant as there is a parallel decrease in the zymogen
      granule amylase content and size.

PMID- 8543914
TI  - Chloride channels in the apical membrane of thyroid epithelial cells are
      regulated by cyclic AMP.
AB  - Porcine thyroid epithelial cells cultured as a monolayer with their apical
      membranes facing the medium are known to absorb Na+ and to secrete the anions Cl-
      and HCO3-. Chloride channels were found in the apical membrane, and displayed a
      reversal potential close to the resting membrane potential, linear current
      voltage relationships, a conductance at physiological temperature of 6.5 pS, and
      a small but significant permeability to HCO3-. Stimulation of ion transport with
      prostaglandin E2 or 8-(4-chlorophenylthio) adenosine 3':5'-cyclic monophosphate
      promoted activation of Cl- channels in cell-attached patches, and excised patches
      were reactivated by exposure of their cytoplasmic surface to protein kinase A and
      ATP. Physiological temperatures were necessary for activation of Cl- channels in
      cell-attached patches. The channels exhibited sub-states with a conductance
      exactly half that of the full unit conductance, suggesting a dual-barrelled
      channel structure. It is concluded that the apical membrane of thyroid epithelial
      cells contains cyclic AMP-activated Cl- channels controlling anion transport.

PMID- 8543915
TI  - Different molecular and messenger ribonucleic acid forms of insulin-like growth
      factor-binding protein-3 in the pregnant baboon (Papio anubis).
AB  - The ratio of the serum concentrations of insulin-like growth factors (IGF) to IGF
      binding protein (IGFBP)-3 is highly correlated (Baxter & Martin 1986). During
      pregnancy in the baboon, this ratio is perturbed; serum IGFBP-3 concentrations
      increase 10-fold, yet IGF-I levels are unaltered and IGF-II is increased only 2
      fold (Giudice et al. 1993). The aims of this study were to determine the
      molecular distribution of IGFBP-3 and to identify the tissue source and form(s)
      of IGFBP-3 during pregnancy in the baboon. Serum of non-pregnant and pregnant
      baboons, and conditioned media of decidua and placental explant cultures were
      characterized using neutral size-exclusion chromatography in combination with
      Western ligand blot, Western immunoblot, an IGFBP-3 radioimmunoassay (RIA) and an
      IGFBP-3 protease assay. Localization of immunoreactive IGFBP-3 was determined by
      immunocytochemistry, and expression of IGFBP-3 mRNA in the placental and decidual
      explants was examined by Northern blot analysis. RIA confirmed that
      immunoreactive IGFBP-3 is increased 10-fold in pregnancy serum compared with non
      pregnancy serum. Size-exclusion chromatography combined with an IGFBP-3 RIA
      revealed that, unlike non-pregnancy serum where 70% of the immunoreactive IGFBP-3
      elutes in the 150 kDa ternary complex, equal amounts of immunoreactive IGFBP-3
      were measured in pregnancy serum in the < or = 150 and 60 kDa IGFBP regions.
      Western analysis revealed that non-pregnancy serum contained predominantly a 45
      40 kDa IGFBP-3 doublet and a 28 kDa immunoreactive form of IGFBP-3, while in
      pregnancy serum IGFBP-3 existed as a 45-40 kDa doublet, as well as 26-28 kDa and
      18 kDa immunoreactive forms. These alternative forms of IGFBP-3 were not
      attributable to detectable IGFBP-3 protease activity. To identify the source of
      the increased serum levels of IGFBP-3 during pregnancy, we examined explant
      culture media of baboon decidua and placenta. Size-exclusion chromatography
      combined with RIA and Western analysis revealed that: (1) more immunoreactive
      IGFBP-3 was produced by decidual cultures than by placental explants, but less 45
      40 kDa IGFBP-3 was present in decidua; (2) the immunoreactive forms of IGFBP-3
      detected in decidua were similar to those found in maternal serum; (3) placental
      explants secreted only 45-40 kDa IGFBP-3 in culture. IGFBP-3 was
      immunohistochemically localized to the cells of placental villi, and to the
      perinuclear region of the decidual cells and staining for IGFBP-3 was more
      intense in the decidua than in the placenta. Northern analysis of the explant
      cultures revealed two IGFBP-3 mRNA transcripts of 2.4 and 1.7 kb in both decidua
      and placenta which may account for the different immunoreactive forms of IGFBP-3
      detected in the baboon. However analysis of non-pregnancy liver also revealed two
      IGFBP-3 transcripts of 2.4 and 1.7 kb. These data suggest that the two
      transcripts are not solely pregnancy-associated and levels of protein may be the
      reason for detection of multiple immunoreactive IGFBP-3 fragments in pregnancy.

PMID- 8543916
TI  - Role of testicular macrophages in the response of Leydig cells to gonadotrophins
      in young hypophysectomized rats.
AB  - The Leydig cells of young hypophysectomized rats are highly sensitive to the
      stimulatory effects of exogenous pituitary hormones. The aim of this study was to
      analyse the role of testicular macrophages in the response of Leydig cells to
      different hormones. Male rats were hypophysectomized at 28 days of age and 10
      days later they were injected intratesticularly with dichloromethylene
      diphosphonate-containing liposomes (right testis) to deplete testicular
      macrophages, and with 0.9% NaCl (left testis). One week later, the animals were
      treated daily with 1 IU rat GH (rGH)/rat, 5 IU recombinant human FSH
      (recFSH)/rat, 10 IU human chorionic gonadotrophin (hCG)/rat, or vehicle for 7
      days. The animals were killed on the day after the last injection. The animals
      treated with rGH showed increased body weight and increased number and size of
      testicular macrophages in the left testes, but no significant effects on Leydig
      cells were found. Treatment with recFSH induced a significant increase in
      testicular weight and tubular diameter in both testes. In the left testes, the
      number and size of macrophages were increased; the number of Leydig cells was not
      changed, although they showed a significantly increased cross-sectional area.
      This effect was abolished in the right (macrophage-depleted) testes. However, the
      effect of recFSH on the growth of the seminiferous tubules was not modified by
      the absence of macrophages. Rats treated with hCG showed increased testicular
      weight and serum testosterone levels, as well as an increased weight of the
      ventral prostate. In the left testes, the number and size of both macrophages and
      Leydig cells were increased. Otherwise, the number of Leydig cells was unchanged
      in the absence of macrophages, whereas the increase in the size of Leydig cells
      was partially abolished. These data indicate that testicular macrophages are
      needed for the response of Leydig cells to gonadotrophin treatment.

PMID- 8543917
TI  - Devazepide reverses the anorexic effect of simmondsin in the rat.
AB  - Simmondsin, a glycoside extracted from jojoba meal (Simmondsia chinensis), causes
      a reduction in food intake after oral administration. To investigate the
      mechanism by which simmondsin reduces food intake, fasted and free-feeding rats
      were given simmondsin-supplemented food and simultaneously injected with
      devazepide, a specific antagonist of peripheral-type cholecystokinin receptors
      (CCKA receptors). In free-feeding rats, supplementation of food with 0.5%
      simmondsin caused a reduction in food intake of +/- 40% in the period of 4 h
      following food presentation. Intraperitoneal injection of 100 micrograms
      devazepide/kg body weight prevented this effect. In rats fasted for 20 h, the
      food intake in the 30 min after presentation of food supplemented with 0.15% or
      0.50% simmondsin was reduced in a dose-related manner; this was also inhibited by
      simultaneous application of devazepide. It is suggested that peripheral CCKA
      receptors are involved in the effect of simmondsin on food intake. However, a
      direct effect of simmondsin on CCKA receptors has been excluded, since simmondsin
      was unable to cause contraction of the guinea-pig gallbladder in vitro.

PMID- 8543918
TI  - Differences in cellular transport of tri-iodothyronine and thyroxine: cell cycle
      dependent alteration of tri-iodothyronine uptake.
AB  - Cellular and nuclear uptake of tri-iodothyronine (T3) and thyroxine (T4) was
      examined using the cultured cell line derived from rat liver, clone 9, and rat
      hepatoma, dRLH-84. The saturable cellular uptake of T3 and T4 was demonstrated in
      these cells. First we examined the cell cycle-dependent alteration of thyroid
      hormone uptake. Cellular T3 uptake was minimal in the early G1 phase and
      increased in the late G1 phase, reaching a maximal level in the S phase.
      Alterations in nuclear T3 uptake were in accordance with the changes in cellular
      T3 uptake. On the other hand, cellular and nuclear T4 uptake was unchanged
      throughout the cell cycle, suggesting the T3 specificity of the cell cycle
      dependent alteration of cellular hormone transport. Next we examined the effect
      of sodium butyrate on the cellular transport of thyroid hormones. After treatment
      with 5 mM sodium butyrate, cellular and nuclear uptake of T3 was increased,
      reaching a maximal level (four- to sevenfold increase) after 48 h. When cells
      were incubated for 48 h with various concentrations of sodium butyrate, T3 uptake
      was enhanced by 1 mM sodium butyrate, reaching a maximal level with 5 mM.
      Although cellular T4 uptake was also increased after treatment with sodium
      butyrate, the degree and time-course of the increase were different from those of
      T3. The maximal increase in cellular T4 uptake (two- to threefold increase) was
      attained 20 h after treatment. Despite the increase in cellular T4 uptake,
      nuclear T4 uptake was decreased after treatment with sodium butyrate. For both T3
      and T4, the enhanced cellular uptake was due to the increased Vmax without
      changes in the Michaelis-Menten constant. These data indicate that cellular
      transport of T4 is different from that of T3 in rat hepatic cells.

PMID- 8543919
TI  - Ontogeny of the expression and regulation of interleukin-6 (IL-6) and IL-1 mRNAs
      by human trophoblast cells during differentiation in vitro.
AB  - During human placental differentiation, mononuclear cytotrophoblast cells fuse
      and differentiate into syncytiotrophoblast cells. Although syncytiotrophoblast
      cells have been shown to express interleukin-1 alpha (IL-1 alpha), IL-1 beta and
      IL-6, the pattern of expression of these cytokines during placental
      differentiation is unknown. We have examined the expression of IL-1 alpha, IL-1
      beta and IL-6 mRNA during differentiation of cytotrophoblast cells in culture. IL
      1 alpha, IL-1 beta and IL-6 mRNA levels were determined by semiquantitative
      reverse transcription-PCR analysis using glyceraldehyde phosphate dehydrogenase
      as an internal control. All three cytokine mRNA levels decreased markedly during
      trophoblast differentiation. After 6 days in culture, when almost all the
      cytotrophoblast cells had fused and differentiated into syncytiotrophoblast
      cells, the amounts of IL-1 alpha, IL-1 beta and IL-6 mRNA were decreased by 87.1,
      72.1 and 60.9% respectively. Exogenous IL-6 had differential effects on cytokine
      mRNA expression. When added to placental cultures during the first 6 days of
      culture, IL-6 markedly inhibited IL-6, IL-1 alpha and IL-1 beta mRNA expression.
      However, when added to the cells during days 6-9 of culture, when most of the
      cells were syncytiotrophoblast cells, IL-6 stimulated IL-1 alpha and IL-1 beta
      mRNA expression. The results of these studies indicate that IL-1 alpha, IL-1 beta
      and IL-6 mRNA expression decreases markedly during cytotrophoblast
      differentiation in vitro and that the regulation of trophoblast cytokine mRNA
      levels changes during differentiation.

PMID- 8543920
TI  - Developmental expression of the prolactin receptor gene in rat gonads.
AB  - The prolactin receptor (PRLR) is a member of the cytokine/prolactin/GH receptor
      family, and it is widely expressed in various mammalian tissues. Expression of
      the two different forms of PRLR, differing in the length of their cytoplasmic
      domains, was studied in rat gonads during fetal and postnatal development. The
      two forms of PRLR mRNA were analyzed by reverse transcription (RT)-PCR using
      primer pairs specific for the different forms. The specificity of the cDNA
      species generated by RT-PCR was verified by Southern hybridization using nested
      32P-labeled oligonucleotides. The results indicated that both forms of PRLR mRNA
      are expressed in the rat testis and ovary, which is in agreement with previous
      reports. The onset of expression of the two PRLR forms occurs on day 14.5 of
      fetal life in rat testis. In the ovary, the long form of PRLR mRNA appears 1 day
      before the short form, i.e. these forms begin to be expressed on fetal days 14.5
      and 15.5 respectively. In situ hybridization with antisense cRNA probes specific
      to each form of the PRLR mRNAs demonstrated specific hybridization of both forms,
      localized in Leydig cells from day 18.5 of fetal life and at the postnatal ages
      studied. Compared with our previous findings concerning the ontogeny of LH
      receptor gene expression, PRLR gene expression starts earlier in development and
      exhibits no sexual dimorphism. The presence of two forms of PRLR mRNA in the
      fetal gonads suggest that they might play differential roles in gonadal
      development and function.

PMID- 8543921
TI  - Differential regulation of plasma levels of insulin-like growth factors-I and -II
      by nutrition, age and growth hormone treatment in sheep.
AB  - Plasma levels of IGFs-I and -II were measured in 4-month-old ewe lambs (n = 20)
      and 2-year-old ewes (n = 16), which were well fed (n = 18) or fasted (n = 18) for
      3 days. Half of each nutrition group was given daily (0900 h) injections of
      bovine GH (bGH, 0.1 mg/kg body weight per day) for 3 days. Blood samples were
      collected immediately before the GH injection every morning. Plasma IGFs were
      extracted by acid gel permeation chromatography using a Waters Protein Pak 125
      column, fitted to a Pharmacia fast protein liquid chromatography system, then
      freeze-dried, reconstituted (at pH 7.4) and estimated by RIA. At the end of the
      experiment, IGF-I levels in plasma were increased (P < 0.01) by exogenous bGH in
      both fed ewes and lambs but not in the fasted animals; plasma IGF-I levels were
      depressed by fasting (P < 0.01) at all ages. IGF-I levels were also found to be
      significantly higher (P < 0.01) in ewes than lambs. In contrast, plasma IGF-II
      concentrations were depressed (P = 0.02) by administration of bGH in all groups
      and elevated in the ewes (P < 0.05) by fasting. However, the lambs showed no
      significant changes in IGF-II with fasting. The IGF-II levels were significantly
      higher (P < 0.001) in lambs than ewes. Results from the present study demonstrate
      that GH administration stimulated an increase in plasma IGF-I and induced a
      decrease in plasma IGF-II. On the other hand, fasting depressed plasma IGF-I and
      elevated plasma IGF-II in the sheep. A significant GH/nutrition interaction for
      IGF-I (P < 0.01), but not for IGF-II, and a significant nutrition/age interaction
      for IGF-II (P < 0.01), but not for IGF-I, in the present study suggest that GH
      has a greater stimulating effect on plasma levels of IGF-I in the fed rather than
      fasted sheep and that nutrition has a greater influence on plasma levels of IGF
      II in the older rather than younger animals, indicating that plasma IGFs-I and 
      II are differentially regulated by nutrition, GH and developmental stage in
      postnatal sheep.

PMID- 8543922
TI  - Could abnormalities in insulin-like growth factors and their binding proteins
      during pregnancy result in gestational diabetes?
AB  - A number of dramatic changes have been documented in the insulin-like growth
      factors (IGFs-I and -II) and their binding proteins (IGFBPs) during pregnancy. In
      this study we have tested the hypothesis that a failure of the normal proteolytic
      modification of IGFBP-3 is responsible for gestational diabetes by examining
      serum samples taken in the third trimester from 29 women with uncomplicated
      pregnancies, 21 women with established Type 1 diabetes and 20 women with
      gestational diabetes. Analysis of IGFBP-3 by Western immunoblotting revealed that
      it was present in a modified form, migrating at around 29 kDa, in the circulation
      of all of the women investigated. Semiquantification of the activity of the
      protease which modifies the IGFBP-3 demonstrated considerable variation between
      individuals in their ability to fragment radiolabelled IGFBP-3 following a 45-min
      co-incubation. Surprisingly, in one individual (with gestational diabetes) there
      was no detectable protease activity even though her endogenous IGFBP-3 had been
      modified. However, overall there was no clear-cut difference in protease activity
      between the different groups. Radioimmunometric analysis of IGF-I revealed
      significantly higher levels in women with gestational diabetes than either of the
      other two groups (P < 0.05). Similarly IGFBP-3 levels were also increased in
      these same women (P < 0.05). In contrast, IGF-II levels did not alter between the
      three groups. In conclusion, our hypothesis was not supported by these data and
      gestational diabetes was found not to be associated with any reduction in the
      activity of the circulating IGFBP-3 protease which could have decreased the
      availability of the IGF nor with any alteration in IGFs which could explain the
      onset of diabetes in these women.

PMID- 8543923
TI  - Bioactive oxytocin in human and baboon corpora lutea.
AB  - Oxytocin has been identified in both non-human primate and human corpora lutea of
      the menstrual cycle by RIA, immunocytochemistry and HPLC. Evidence for the
      transcription of the oxytocin gene in this tissue using PCR is available.
      Oxytocin receptors have been characterized by biochemical procedures. However,
      there is some debate as to whether the oxytocin identified in these tissues is
      biologically active and has a role in luteal function. In this study we have
      demonstrated that oxytocin isolated by gel chromatography of tissue extracts from
      the baboon and the human corpus luteum is biologically active as determined in a
      rat uterine bioassay. Since both oxytocin and its receptors are present in these
      tissues, it is suggested that oxytocin in the human and non-human primate corpora
      lutea has a functional role.

PMID- 8543924
TI  - Dexamethasone inhibits the release of TSH from the rat anterior pituitary gland
      in vitro by mechanisms dependent on de novo protein synthesis and lipocortin 1.
AB  - Glucocorticoids have been shown repeatedly to inhibit the secretion of TSH in
      experimental animals and in man but their site and mode of action are unknown. In
      the present study, we have used an in vitro model to examine the effects of
      dexamethasone on the resting and pharmacologically evoked secretion of TSH by the
      rat anterior pituitary gland, and to show how they are influenced by inhibitors
      of RNA/protein synthesis. In addition, we have investigated the potential role of
      lipocortin 1 (LC1), a protein shown previously to contribute to glucocorticoid
      action in several systems, as a mediator of the glucocorticoid-induced
      suppression of TSH release in our in vitro preparation. The significant (P <
      0.01) increases in the release of immunoreactive (ir)TSH from rat anterior
      pituitary tissue initiated by submaximal concentrations of TRH (10 nmol/l),
      vasoactive intestinal polypeptide (VIP, 10 nmol/l) or the adenyl cyclase
      activator, forskolin (100 mumol/l) were reduced significantly (P < 0.05) by
      preincubation of the tissue with dexamethasone (0.1 mumol/l). In contrast, irTSH
      secretion evoked by a submaximal concentration of the L-Ca2+ channel opener BAY
      K8644 (10 mumol/l) was unaffected by the steroid, although readily antagonised (P
      < 0.01) by nifedipine (1-100 mumol/l). Inclusion of actinomycin D (1.78 mumol/l)
      or cycloheximide (0.8 mumol/l), inhibitors of RNA and protein synthesis
      respectively, in the medium effectively abrogated the inhibitory effects of
      dexamethasone (0.1 mumol/l) on the secretory responses to TRH (10 nmol/l), VIP
      (10 nmol/l) and forskolin (100 mumol/l). LC1 was readily detectable by Western
      blotting in protein extracts of freshly excised anterior pituitary tissue. A
      small proportion of the protein was found to be attached to the outer surface of
      the cells where it was retained by a Ca(2+)-dependent mechanism. Exposure of the
      tissue to dexamethasone (0.1 mumol/l) caused a pronounced increase in the amount
      of cellular LC1 attached to the outer surface of the cells and a concomitant
      decrease in the intracellular LC1 pool. Progesterone (0.1 mumol/l) and
      aldosterone (0.1 mumol/l) were also weakly active in this regard, but thyroxine
      and tri-iodothyronine (0.1 mumol/l) were not. Addition of an N-terminal LC1
      fragment, LC1(1-188) (0.05-0.53 pmol/l) to the incubation medium reduced
      significantly (P < 0.01) the increases in irTSH release induced by TRH (10
      nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l), but failed to influence (P
      < 0.05) those initiated by BAY K8644 (10 mumol/l). Furthermore, the inhibitory
      actions of dexamethasone (0.1 mumol/l) on the release of irTSH provoked by TRH
      (10 nmol/l), VIP (10 nmol/l) and forskolin (100 mumol/l) were substantially
      reversed (P < 0.01) by a specific monoclonal anti-LC1 antibody, while an isotype
      matched control antibody was without effect. The results show clearly that
      dexamethasone, a semi-synthetic glucocorticoid, acts at the pituitary level to
      inhibit the neurochemically evoked release of irTSH. They also provide novel
      evidence that the inhibitory actions of the steroid are dependent upon de novo
      RNA/protein synthesis and that they involve an LC1 dependent mechanism.

PMID- 8543925
TI  - Stimulation of hepatic insulin-like growth factor-binding protein-1 and -3 gene
      expression by octreotide in rats.
AB  - It has recently been demonstrated in various clinical experiments that native
      somatostatin and its long-acting analogues increase circulating levels of insulin
      like growth factor-binding protein-1 (IGFBP-1) within 1-2 h, independent of
      effects on circulating insulin or glucose levels. Using human hepatoma cells in
      vitro the somatostatin analogue, octreotide, has been shown to increase IGFBP-1
      mRNA within 24 h indicative of a direct stimulatory effect of octreotide on IGFBP
      1 synthesis. In order to ascertain whether octreotide acutely stimulates IGFBP-1
      mRNA in vivo, placebo or two doses of octreotide were injected subcutaneously
      into three groups of rats. One hour after saline or octreotide administration,
      liver, kidney and serum were obtained for the measurement of IGFBPs-1 to -6 mRNA
      in tissue and IGFBPs and IGF-I in serum. Octreotide increased liver IGFBP-1
      (562%) and IGFBP-3 (23%) mRNA expression with a concomitant rise in the
      circulating 30 kDa (106%) and 38-42 kDa (23%) IGFBPs. No detectable changes were
      seen in other liver IGFBP transcripts, other circulating IGFBPs or in any of the
      kidney IGFBP transcripts. Serum IGF-I increased by 37% in the animals receiving
      the high octreotide dose. No concomitant changes were observed in glucose or
      insulin levels. These data show that octreotide acutely stimulates hepatic IGFBP
      1 and -3 mRNA in vivo in rats. The stimulating effect on IGFBP-3 presents a
      possible hitherto unknown form of regulation of IGFBP-3 whilst the effect on
      IGFBP-1 indicates that the stimulatory effect of octreotide on circulating IGFBP
      1 described in clinical trials may be due to increased hepatic production. The
      present findings may be of importance in the clinical use of octreotide.

PMID- 8543926
TI  - Menstrual cycle specific expression of epidermal growth factor receptors in human
      fallopian tube epithelium.
AB  - We studied the expression of epidermal growth factor (EGF) receptor protein and
      messenger RNA (mRNA) in human fallopian tubes at three stages of the menstrual
      cycle: early follicular (n = 3), late follicular (n = 3) and luteal (n = 3).
      Immunohistochemical studies in the ampullary portion of the tubes showed that
      specific staining was localized to the epithelium and the vascular endothelium.
      Staining of the epithelium was intense at the late follicular and luteal stages,
      while it was weak at the early follicular stage. 125I-EGF binding study in the
      tubal plasma membranes revealed a class of high-affinity EGF receptors. Although
      dissociation constants were similar between the stages, numbers of binding sites
      at the late follicular and luteal stages were significantly (P < 0.01) greater
      than those at the early follicular stage. Western blotting showed that tubal
      plasma membranes contain M(r) 170,000 EGF receptor protein. The amounts were
      significantly (P < 0.01, n = 3) greater at the late follicular and luteal stages
      than those at the early follicular stage. Reverse transcription and polymerase
      chain reaction (RT-PCR) revealed that EGF receptor mRNA was expressed in all the
      9 RNA samples (n = 3 for each stage) from the tubal ampullary portion. The
      amounts were significantly (P < 0.01, n = 3) greater at the late follicular and
      luteal stages than those at the early follicular stage (by a competitive PCR).
      Increase in the amounts of EGF receptor protein and mRNA occurred in association
      with an increase in serum oestradiol but not progesterone levels. Next we
      examined whether EGF receptor and its ligands (EGF and transforming growth factor
      alpha) are directly induced by oestrogen. We found that specific staining for EGF
      receptor and its ligands in the tubal epithelium was detected (by
      immunohistochemistry) in postmenopausal women with oestrogen replacement (n = 3),
      but not in subjects without oestrogen replacement (n = 3). These results
      suggested that EGF receptors in the human tubal epithelium are expressed in
      relation to specific stages of the menstrual cycle and that the expression may be
      induced by oestrogen.

PMID- 8543927
TI  - The role of neuropeptide Y (NPY) in the control of LH secretion in the ewe with
      respect to season, NPY receptor subtype and the site of action in the
      hypothalamus.
AB  - Neuropeptide Y1-36 (NPY1-36) acts through Y1 and Y2 receptors while the C
      terminal NPY fragments NPY18-36 and N-acetyl[Leu28,31]pNPY24-36 act only through
      the Y2 receptor. We have investigated the effects of intracerebroventricular
      (i.c.v.) administration of NPY1-36, NPY18-36 and N-acetyl[Leu28,31]pNPY24-36 on
      LH secretion in the ovariectomised (OVX) ewe. These peptides were administered
      into a lateral ventricle (LV) or the third ventricle (3V) of OVX ewes during the
      non-breeding and breeding seasons. Microinjections of NPY were also made into the
      preoptic area (POA) during both seasons to investigate the effects of NPY at the
      level of the GnRH cell bodies. Tamed sheep were fitted with 19 gauge guide tubes
      into the LV, 3V or the septo-preoptic area (POA). Jugular venous blood samples
      were taken every 10 min for 3 h. Sheep were then given NPY1-36 (10 micrograms),
      NPY18-36 (100 micrograms) or saline vehicle into the LV; N-acetyl[Leu28,31]pNPY24
      36 (100 micrograms), NPY1-36 (10 micrograms or 100 micrograms), NPY18-36 (10
      micrograms or 100 micrograms) or saline vehicle into the 3V, or NPY1-36 (1
      microgram, 5 micrograms, 10 micrograms) into the POA. Blood sampling continued
      for a further 3 h. LH was measured in plasma by radioimmunoassay. LV or 3V
      injection of 10 micrograms NPY1-36 caused a small but significant (P < 0.025)
      increase in the interval from the last pre-injection pulse of LH to the first
      post-injection LH pulse during the breeding season. Other LH pulse parameters
      were not significantly affected. NPY18-36 did not produce any significant change
      in LH pulsatility when injected into the LV, and neither peptide had any effect
      on plasma prolactin or GH levels. There was a significant (P < 0.01) reduction in
      LH pulse frequency after 3V injection of 10 micrograms and 100 micrograms NPY and
      100 micrograms NPY18-36. Pulse amplitude was reduced by 3V administration of the
      Y2 agonist, N-acetyl[Leu28-31]pNPY24-36 and 100 micrograms NPY18-36. When the
      amplitude of the first post-injection LH pulse was analysed, 10 micrograms NPY
      also had a significant (P < 0.05) suppressive effect. During the non-breeding
      season, 100 micrograms NPY1-36 (but not 10 micrograms) decreased (P < 0.01) LH
      pulse frequency. LH pulse amplitude was significantly (P < 0.01) decreased by 100
      micrograms NPY18-36. Doses of 10 micrograms NPY1-36 and 100 micrograms NPY18-36
      had greater inhibitory effects on pulse frequency during the breeding season but
      the suppressive effect of 100 micrograms NPY was similar between seasons.
      Microinjections of NPY into the POA decreased (P < 0.01) average plasma LH levels
      during the non-breeding season at a dose of 10 micrograms but did not
      significantly affect pulse frequency or amplitude. We conclude that a substantial
      component of the inhibitory action of NPY on LH secretion in the absence of
      steroids is mediated by the Y2 receptor. This inhibition is probably exerted by
      way of a presynaptic action on GnRH terminals in the median eminence as NPY does
      not modulate the frequency or amplitude of LH pulses at the level of the GnRH
      cell bodies in the POA.

PMID- 8543929
TI  - Toddlers' emotion regulation behaviors: the roles of social context and family
      expressiveness.
AB  - Fifty-five toddlers (mean age = 17.7 months) were observed in a modified strange
      situation that included their preschool-age older siblings (mean age = 50.6
      months). The toddlers were observed while interacting with their older siblings
      and again with the siblings and a stranger. Differences in the toddlers'
      emotional lability, latency to distress, self-soothing behavior, and comfort
      seeking behavior across the two situations were examined. The linkage between the
      family's reported expression of positive emotion, sadness, and anger and the
      toddlers' emotion regulation behaviors was evaluated. The results revealed that
      the toddlers were more emotionally regulated in the presence of the siblings and
      the stranger than when they were alone with their siblings. In addition, mother
      reported positive expressiveness within the family was related to higher levels
      of self-soothing behavior in the siblings-alone condition, and mother-reported
      sadness within the family was inversely related to toddlers' self-soothing
      behavior in both conditions. The results are discussed in terms of the importance
      of social-context factors and family expressiveness for the development of
      emotion regulation.

PMID- 8543928
TI  - Childhood aggression and unconventionality: impact on later academic achievement,
      drug use, and workforce involvement.
AB  - The interrelation of childhood aggression, unconventionality, academic
      orientation, work involvement, and drug use was explored. Data were obtained for
      the research participants when they were 5 to 10 years old. Follow-up interviews
      were conducted when the participants were 15 to 20 years old and again at 21 to
      26 years old. Latent variable causal analysis was used, and the findings reveal
      long-term relations between early childhood aggression and adolescent problem
      behavior in the academic and occupational areas. The findings also indicate that
      adolescent drug use generates an early involvement with adult role behaviors,
      such as work at the expense of further education. Implications of the findings
      for prevention are discussed.

PMID- 8543930
TI  - Maternal factors related to parenting practices, developmental expectations, and
      perceptions of child behavior problems.
AB  - Parenting practices of a representative sample of 1,056 urban mothers with very
      young children were studied via the Parent Behavior Checklist (Fox, 1994) and the
      Behavior Screening Questionnaire (Richman & Graham, 1971). Potential determinants
      of parenting practices were also addressed, including maternal age, marital
      status, education level, number of children living at home, and family
      socioeconomic status. Less positive parenting practices concerning nuturing and
      discipline were found among mothers who were younger, had more than one child
      living at home, were single, had a lower income level, and had lower educational
      attainment. These mothers also tended to perceive their children as demonstrating
      more difficult behavior problems. However, the negative influence of some
      determinants of parenting practices, such as low income, was found to be
      moderated by the presence of other determinants, such as more education. The
      present results provide evidence that multiple determinants influence parenting
      practices among parents of young children.

PMID- 8543931
TI  - Maternal social and physical contact: links to early infant attachment behaviors.
AB  - The relationship between maternal physical and social contact styles and infant
      attachment behavior under stress and nonstress conditions was studied at 2
      different age points during the 1st year of life. The infants (29 girls and 15
      boys) and their mothers were observed in their homes at 4 and 7 months of age.
      Maternal physical and social contact behaviors during an unstructured observation
      were rated on the Clarke-Stewart Rating Scales. Infant attachment behaviors in
      semistructured interactions with their mothers and with a stranger were rated on
      the Attachment Indicators Rating Scale. Scores on all attachment behaviors were
      subjected to a principal-axes factor analysis with varimax rotation, and one-way
      analyses of variance were conducted to assess effects of maternal social and
      physical contact at 4 and 7 months. A significant link was found between maternal
      physical contact at 4 months and the infant's attachment behavior under
      conditions of stress and play at both 4 and 7 months. Maternal social contact at
      4 months was linked to attachment behavior in play situations, but not in stress
      situations. By the age of 7 months, the infants' attachment behavior under both
      stress and play conditions was linked to concurrent social and physical maternal
      contact. Maternal physical and social contacts at 4 and 7 months were linked to
      concurrent infant proximal attachment behavior, but such contacts at 4 months
      were not predictive of later infant proximal behaviors. These findings suggest
      that the relationship between the intensity and style of maternal contact and
      infant attachment behavior varies with age.

PMID- 8543932
TI  - Onset vulnerability to depression.

PMID- 8543933
TI  - Pentoxifylline ameliorates postischemic delayed hypoperfusion of the cerebral
      cortex following cardiac arrest in cats.
AB  - Two major events occurring in the cerebral hemodynamics after successful
      resuscitation from cardiac arrest are reactive hyperemia and postischemic
      hypoperfusion. We examined the effect of pentoxifylline on the feline cerebral
      hemodynamics following cardiac arrest. Fifteen cats were anesthetized and
      artificially ventilated. Using our photoelectric method, the local cerebral blood
      volume (CBV), mean transit time of blood (MTT), and cerebral blood flow (CBF) in
      the parietotemporal region were measured. Thoracotomy was performed, and cardiac
      arrest (ventricular fibrillation) was induced by direct application of a 2-V DC
      countershock. The heart was resuscitated with a DC countershock at 30 sec after
      cardiac arrest. In 9 cats, pentoxifylline (25 mg/kg) was infused into the femoral
      vein at 5 min before cardiac arrest (PTX group). The other 6 cats served as
      controls (control group). In both groups, the CBV, CBF and mean arterial blood
      pressure (MABP) overshot the control levels just after resuscitation, whereas the
      MTT was decreased. In the control group, postischemic hypoperfusion was detected
      at 30-180 min after resuscitation from cardiac arrest (CBF (ml/100 g/min): 51 +/-
      4 (control), 38 +/- 4 (30 min, p < 0.05), and 23 +/- 3 (180 min, p < 0.05)).
      However, the postischemic hypoperfusion was not observed in the PTX group.
      Pentoxifylline ameliorated postischemic delayed hypoperfusion in the cerebral
      cortex after a short period of cardiac arrest. Pentoxifylline may be useful in
      the emergency situations following cardiac arrest.

PMID- 8543934
TI  - Brain tumor and exposure to pesticides in humans: a review of the epidemiologic
      data.
AB  - We examined the relationship between exposure to pesticides and the subsequent
      development of brain tumors in adults through a critical review of the
      literature. The results of retrospective case-control studies are conflicting, in
      part because of biases in the selection of patients and controls, poor definition
      and ascertainment of the nature and extent of the exposure to pesticides, and a
      non-uniform approach to the collection of antecedent information. A number of the
      studies evaluated farmers as a group exposed to pesticides; however, inference
      about cancer incidence in farmers may reflect not only their possible exposure to
      pesticides, but also exposure to petrochemical products, exhaust fumes, mineral
      and organic dusts, and biological exposure to animals and microbes. The great
      majority of the cohort studies of chemical workers employed in the manufacture of
      pesticides did not indicate an excess of brain cancer mortality. There have been
      few cohort studies of pesticide applicators and these revealed elevated but non
      significant relative risks for excess mortality due to brain cancer. Existing
      data are insufficient to conclude that exposure to pesticides is a clear risk
      factor for brain tumors. Given the conflicting results reported for farmers and
      pesticide applicators and their contrast to chemical workers, it seems more
      plausible that exposure to multiple agents and/or other factors, such as genetic
      predisposition, are most relevant with respect to brain tumor pathogenesis.

PMID- 8543935
TI  - Anti-dorsal root ganglion neuron antibody in a case of dorsal root ganglionitis
      associated with Sjogren's syndrome.
AB  - We report the case of a 59-year-old woman with primary Sjogren's syndrome who
      developed hypesthesia, hypalgesia, and neurogenic arthropathy in her lower limbs.
      Neurological examination and electrophysiological studies indicated involvement
      of the dorsal root ganglia. The immunohistochemistry of sections of rat dorsal
      root ganglion (DRG) showed that the IgG in the serum and cerebrospinal fluid
      (CSF) from the patient bound to the neuronal perikarya of small DRG neurons but
      not to the cerebellum or peripheral nerves. These results, consistent with
      particular impairment of pain and touch senses, suggest that dorsal root
      ganglionitis in primary Sjogren's syndrome is mediated by humoral autoimmunity.

PMID- 8543936
TI  - Investigation of a null mutation of the CNTF gene in familial amyotrophic lateral
      sclerosis.
AB  - Neurotrophic factors, such as ciliary neurotrophic factor (CNTF), have been
      implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a human
      neurodegenerative disease primarily of upper and lower motor neurones. A null
      mutation of the CNTF gene has recently been described. The mutation is an
      intronic point mutation (G to A) which generates a new splice acceptor site and a
      4 bp insertion within the CNTF coding region, and prevents the expression of the
      normal protein. We investigated this as a candidate gene in 49 families with ALS,
      where the genetic component may be expected to be strongest. 65% were normal
      homozygotes, and 35% were heterozygotes for the mutation. No mutant homozygotes
      were detected. The absence of CNTF protein expression associated with the
      homozygote mutation does not appear to be of major significance in the
      development of ALS.

PMID- 8543937
TI  - Efficacy of an adenosine antagonist, theophylline, in essential tremor:
      comparison with placebo and propranolol.
AB  - Propranolol, which has long been used as the standard treatment for essential
      tremor, has been compared with placebo and theophylline in ten newly diagnosed
      patients without other, prior drug treatments. Patients were treated for four
      weeks with one drug, followed by placebo for four weeks, and then the second drug
      for the same period, in a blind cross-over trial. Tremor was quantified using the
      volumetric method, and was decreased significantly after one week on propranolol,
      80 mg/day. Theophylline 150 mg/day reduced tremor to the same extent, although
      the improvement was not significant until the second week. Three patients
      reported side effects on propranolol. It is suggested that theophylline may be a
      useful alternative agent in the treatment of essential tremor, probably due to a
      chronic up-regulation of adenosine receptors.

PMID- 8543938
TI  - Clinical correlates of motor performance during paced postural tasks in
      Parkinson's disease.
AB  - Bradykinesia and hypokinesia may both play a significant role in postural
      instability commonly seen in patients with Parkinson's disease. We investigated
      which factor--movement time or movement amplitude--is the more significant
      limiting variable in patients with Parkinson's disease during a paced postural
      task. We also assessed the effect of antiparkinson medication upon these movement
      factors and the degree of correlation with changes in clinical performance.
      Subjects performed paced left-right (L-R) and forward-backward (F-B) continuous
      weight-shifting tasks at slow, medium and fast paces. Ten Parkinson patients were
      studied both OFF and ON their usual antiparkinson medication. Ten age-matched
      healthy controls were also tested and subsequently retested on the same schedule
      as the patients. Movement times and amplitudes were measured and correlated with
      clinical changes in UPDRS motor subscores. Parkinson patients performed similar
      to controls with respect to movement time, but significantly displayed
      underscaled (reduced) movement amplitude. Movement amplitude improved after
      antiparkinson medication, but remained significantly less than that of controls.
      Improvements in L-R movement amplitude correlated with clinical improvements in
      bradykinesia and postural instability, while improved F-B movement amplitude
      correlated only with reduced postural instability. We conclude that hypometric
      movement amplitude, and not abnormal movement time, is the primary abnormality
      observed in Parkinson patients during a paced postural task. Amplitude
      underscaling seems antiparkinson medication-dependent and improvement correlates
      with favorable clinical changes in bradykinesia and postural instability scores.

PMID- 8543939
TI  - Cobalt-55 positron emission tomography in relapsing-progressive multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is an immune-mediated disease of the white matter in the
      brain that can have a progressive course. However, the progression of relapsing
      remitting (RR) MS into relapsing-progressive (RP) MS might represent a more
      fundamental change in disease activity, i.e. decay of vulnerable neurons and
      oligodendrocytes. In RP-MS, this may imply that the major loss of brain tissue
      structure is caused by a combination of demyelination and cellular loss, both of
      which are likely to cause disability in MS. We used the PET isotope cobalt-55
      (Co) as a calcium (Ca) tracer to visualize brain tissue damage, based on the fact
      that Ca influx is essential in both cell death and T-lymphocyte activation in MS.
      The aim of this study was to determine whether Co-PET detects any RP-MS lesions
      and, if so, to assess any correlation with the progression rate (PR) of the
      disease and with MS lesions as detected by MRI. Seven RP-MS patients (Poser) with
      EDSS > 4.0 (Kurtzke) and 7 healthy controls underwent MRI (Miller, Barkhof) and
      Co-PET. Comparison of both image modalities was made by merging. Co-PET lesion
      frequency was assessed and correlated with the PR of the disease. Co-PET
      demonstrated significantly more lesions in the MS brain than in the healthy
      brain, both periventricular and cortical. Every single MRI lesion could be
      retrieved as a Co-PET lesion. The Co-PET lesion frequency correlated
      significantly with PR. Our pilot study possibly suggests Co-PET as a tool in
      estimating disease activity in RP-MS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8543941
TI  - Increased density of dopamine D2 receptors in the putamen, but not in the caudate
      nucleus in early Parkinson's disease: a PET study with [11C]raclopride.
AB  - Striatal dopamine D2 receptors were studied, using positron emission tomography
      (PET), in 10 patients with early Parkinson's disease without any antiparkinsonian
      medication and in 14 healthy controls. [11C]Raclopride was used as ligand and an
      equilibrium method was applied. The maximum count of receptors (Bmax) and their
      dissociation constant (Kd) were calculated according to the Scatchard principle.
      In parkinsonian patients, the Bmax of D2 receptors was increased in the putamen
      contralateral to the predominant symptoms, as compared to the opposite putamen,
      by 33% (p = 0.0008). In the caudate nucleus no significant side to side
      differences was noted. On comparison with age-matched healthy controls, Bmax
      values in the putamen (p = 0.0012) but not in the caudate nucleus contralateral
      to the side of predominant clinical symptoms were increased in PD patients. The
      Kd values were unchanged. The difference in putaminal Bmax values between the
      opposite hemispheres correlated with the difference in the severity of
      parkinsonian motor symptoms between the two body sides (r = 0.69, p = 0.03). The
      present results show that there is both a relative and absolute increase in the
      number of dopamine D2 receptors in the putamen, but not in the caudate nucleus in
      early Parkinson's disease.

PMID- 8543942
TI  - Neurophysiological evaluation of zidovudine in asymptomatic HIV-1 infection: a
      longitudinal placebo-controlled study.
AB  - The effect of early antiretroviral medication with zidovudine on
      neurophysiological functions was evaluated in subjects with asymptomatic HIV-1
      infection. Patients were recruited participants of a larger double-blind
      randomised placebo-controlled treatment trial with zidovudine (Concorde). The
      main outcome measures included: quantitative electroencephalography (QEEG),
      auditory event-related potentials (AEP) and pattern-reversal visual evoked
      potentials (PRVEP), as well as standard clinical, virological and immunological
      markers. No significant impairment and no difference between treatment groups was
      found in visual P100 latency and auditory long-latency P3 responses which is in
      agreement with the absence of neurological and neuropsychological impairment over
      the study period. Significant treatment effects were revealed by quantitative
      electroencephalography (QEEG). While the placebo group showed a significant
      increase in delta and theta slow frequency QEEG activity over the study period,
      slow wave amplitude remained unchanged in the zidovudine group after a mean
      follow-up period of 28 months. In summary, the data provide evidence for a low
      level neuropathological process in asymptomatic HIV-1 infection which can be
      effectively suppressed by antiretroviral medication.

PMID- 8543940
TI  - Dystrophin characterization in BMD patients: correlation of abnormal protein with
      clinical phenotype.
AB  - We have investigated protein expression and genotype in 59 Becker muscular
      dystrophy (BMD) patients. The aim was to identify possible causes of the marked
      variability in phenotype in patients with similar deletions/mutations. The
      patients were examined neurologically and functionally and underwent Manual
      Muscle Testing. Dystrophin expression was analysed by immunohistochemistry and
      western blot using antibodies against six different segments of the protein. DNA
      mutations were investigated by PCR amplification of 30 exons. Based on dystrophin
      expression at the sarcolemma, two groups of patients were identified: group A (29
      patients) with the classic patchy distribution of dystrophin and group B (30
      patients) with absence or reduction of one or more dystrophin portions and
      variable, although mostly normal, expression of the other portions of the
      protein. Dystrophin molecular weight was normal or slightly reduced in group A
      and was variably reduced, generally conspicuously so, in group B. The quantity of
      dystrophin expressed varied markedly in both groups. The pattern of
      immunohistochemical staining in group B patients correlated with milder clinical
      phenotype, suggesting that small dystrophin molecules lacking a portion in the N
      terminus or in the rod domain, are more functional than proteins with normal or
      slightly reduced molecular weight that display the BMD-typical patchy
      distribution at the sarcolemma.

PMID- 8543943
TI  - A correlation study between serum adenosine deaminase activities and peripheral
      lymphocyte subsets in Parkinson's disease.
AB  - Adenosine deaminase (ADA) and its isozyme activities in serum were measured
      together with peripheral lymphocyte subsets in 42 patients with idiopathic
      Parkinson's disease. The total and ADA 2 activities were significantly higher
      than normal controls (p < 0.01). As regards the peripheral lymphocyte subsets,
      the proportion of OKT 10+ cells (activated T lymphocytes) and the proportions of
      interleukin-2 receptor+ and HLA-DR+ cells (mainly activated T lymphocytes) were
      significantly higher than normal controls (p < 0.05, 0.01, 0.01, respectively).
      On the other hand, OKT 10+ cells demonstrated a significant correlation not only
      with total ADA but also with ADA 2 activity. These results suggest that high
      serum ADA activity may be involved in the pathogenesis of Parkinson's disease
      through peripheral T lymphocyte activation.

PMID- 8543944
TI  - A follow-up study on spastic paraparesis in Japanese HAM/TSP.
AB  - We followed 24 patients with HTLV-I-associated myelopathy (HAM) for 4-12 years
      (mean 7 years) and assessed longitudinal changes of their spastic paraparesis by
      Kurtzke's Disability Status Scale (DSS). The DSS score of spastic paraparesis was
      unchanged in 18 patients (75%), advanced (worsened) by two in 1 patient and by
      one in 3 patients, and declined (improved) by one in 2 patients during the follow
      up period. The results demonstrated that HAM presents with a variety of clinical
      courses including spontaneous improvement.

PMID- 8543945
TI  - Gosha-jinki-gan (herbal medicine) in streptozocin-induced diabetic neuropathy.
AB  - Long-established systems of traditional medicine have evolved from systematic
      recordings of human experience over several millennia. Although not strictly
      based on concepts of modern science, they nevertheless are founded on a corpus of
      organised knowledge written in documents, and the evident conclusion is that the
      alleged "trial and error" methodology has provided useful drugs for humans.
      Herbal medicine should be investigated as a potential regimen for diabetic
      neuropathy for the following reasons: (1) diabetic neuropathy remains an
      important clinical problem affecting a significant proportion of diabetic
      subjects without satisfactory treatment; (2) there are multiple pathogenetic
      mechanisms in diabetic neuropathy; and (3) herbal medicine which is a combination
      prescription has unique synergistic and synthetic effects that result from
      interactions between individual herbal components, and may induce a wide range of
      therapeutic potential and utility. Gosha-jinki-gan (GJK), consisting of 10 herbs,
      has been widely used for a regimen of diabetic complications, including
      neuropathy, in Japan. However, the effect of GJK on experimental diabetic
      neuropathy has never been previously evaluated. We examined nerve conduction
      velocity (NCV) and nerve glucose, sorbitol, fructose and myo-inositol levels in
      streptozocin (STZ)-induced diabetic rats that were treated with GJK. After 1 week
      of the STZ injection in 7-9-week-old rats, GJK treatment (100 mg/100 g body
      weight/day) was started orally. At 16 weeks after the STZ injection, the sciatic
      NCV of GJK-treated diabetic rats improved significantly when compared to non
      treated diabetic rats, although they were not yet normalised.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8543946
TI  - Contractile properties in single muscle fibres from chronically overused motor
      units in relation to motoneuron firing properties in prior polio patients.
AB  - The relation between motoneuron firing rate in vivo and maximum velocity of
      unloaded shortening (Vmax) and myosin isoform composition in single chemically
      skinned muscle fibres was investigated in chronically overused motor units. Ten
      patients with loss of a large proportion of the motoneuron pool due to a prior
      polio lesion and compensatory overuse of residual neurones were studied and
      compared with normal individuals. The tibialis anterior muscle (TA) was chosen
      and prior polio patients who used all residual TA motor units at high rates
      during the normal step cycle were selected. In prior polio patients, all motor
      units fired at approximately 40 Hz when maximum voluntary force was reached. A
      common firing rate of 30 Hz yielded 70-90% maximum force. In normal subjects, on
      the other hand, maximum TA force was reached when low threshold units fired at 25
      30 Hz and high threshold units at 50 Hz. Myosin heavy chain (MHC) and light chain
      (MLC) isoforms were resolved by 6% and 12% sodium dodecyl sulphate polyacrylamide
      gel electrophoresis (SDS-PAGE), respectively, and quantified densitometrically.
      In the whole biopsy cross-sections, types I, IIA and IIB MHC proportions were 97,
      3 and 0% in a typical prior polio patient and 65, 25 and 10% in an age- and sex
      matched control subject. Vmax differed significantly (p < 0.001) between type I
      fibres from the patient (0.54 +/- 0.12 ML/s) and the control subject (0.29 +/-
      0.08 ML/s). The composition and relative contents of essential and regulatory MLC
      isoforms differed in single type I MHC fibres from the control subject and prior
      polio patient. 65% of the fibres co-expressed the fast and slow isoform of the
      regulatory light chain (MLC2) in the patient, while this combination was only
      observed in one of the control type I fibres. All prior polio fibres with a Vmax
      higher than 0.45 ML/s, except one, co-expressed MLC2s and MLC2f and the only
      control fibre co-expressing the slow and fast MLC2 isoform had the highest Vmax
      (0.50 ML/s) among control fibres. On the other hand, a high relative content of
      MLC3 was not associated with a high Vmax in type I MHC fibres. It is suggested
      that the composition of fast and slow isoforms of MLC2 has a significant
      modulatory influence on Vmax within type I MHC fibres. This combination of MLCs
      and high Vmax in type I MHC fibres is probably induced by chronic motor unit
      overuse and an altered motoneuron firing pattern.

PMID- 8543947
TI  - Vitamin A and E levels are normal in amyotrophic lateral sclerosis.
AB  - Using high performance liquid chromatography, we measured serum levels of vitamin
      A and E in 10 amyotrophic lateral sclerosis (ALS) patients and 10 matched
      controls and found no statistically significant differences. Correlation
      coefficients in the ALS group showed no significant relationships among the
      variables age, sex, duration, and severity of ALS.

PMID- 8543948
TI  - Early-onset benign limb-girdle myopathy with contractures and facial involvement
      affecting a father and daughter.
AB  - We describe a father and daughter with early-onset benign limb-girdle myopathy
      and contractures of elbows and hands, resembling Bethlem disease. Muscle biopsy
      showed a pattern of dystrophy with non specific mitochondrial changes. In both
      patients there was unusual facial muscle weakness. We discuss the nosologic
      position of Bethlem myopathy and suggest that facial involvement may be an
      additional feature of this disease.

PMID- 8543949
TI  - Parkinson's disease and the environment in early life.
AB  - To explore a possible relationship between environmental factors encountered
      during fetal life and infancy and the later risk of developing Parkinson's
      disease, a case-control study (172 cases, 343 age- and sex-matched controls) was
      carried out in 42 general practices in the eastern part of Hertfordshire,
      England. Information about birthweight and growth during the first year of life
      was obtained for subjects who had been born in Hertfordshire from records made by
      health visitors in the first part of the century. Information concerning size of
      sibship, position in the birth order, type of housing, other features of the
      environment in early life and experience of the common infections of childhood
      was obtained by questionnaire. Neither birthweight, weight at 1 year of age nor
      any aspect of the childhood domestic environment were associated with an altered
      risk of Parkinson's disease. Cases were more likely to recall suffering from
      croup (odds ratio 4.1, 95% CI 1.1 to 16.1) or diphtheria (odds ratio 2.3, 95% CI
      1.2 to 4.7) in childhood than controls but no other infection was associated with
      an increased relative risk for Parkinson's disease. Cases were more likely than
      controls never to have smoked cigarettes (odds ratio 2.0, 95% CI 1.1 to 3.6). The
      results of this study do not suggest that poor growth in fetal life or infancy is
      important in the aetiology of Parkinson's disease but they hint that early
      infection might partly determine susceptibility to the disease.

PMID- 8543950
TI  - Prognosis of amyotrophic lateral sclerosis and the effect of referral selection.
AB  - We followed two cohorts of Amyotrophic Lateral Sclerosis (ALS) patients to
      examine the survival and prognostic factors of ALS and the impact of selective
      referral on prognosis of ALS. The first cohort consisted of population-based
      incident ALS cases from Harris County, Texas, first diagnosed between 1985 and
      1988. The second was a clinical series from a tertiary care center in Houston,
      Texas, diagnosed between 1977 and 1989. The overall 3-year survival was 29% in
      the incidence cohort and 32% in the referral cohort; however, the 5-year survival
      was much lower for the incidence cohort than the referral cohort (4% vs 21%). The
      large difference in 5-year survival was not explained by the distributions of
      prognostic factors in the two cohorts but due to stronger unfavorable effects of
      prognostic factors in the incidence cohort than the referral cohort. In both
      cohorts, older age at diagnosis, bulbar onset, and positive family history of ALS
      were unfavorable prognostic factors while blacks had better survival than whites
      or hispanics. We confirmed that longer duration from onset to diagnosis was a
      favorable prognostic factor in both cohorts but the effect was more pronounced in
      the referral series.

PMID- 8543951
TI  - Decrease of medullary catecholaminergic neurons in multiple system atrophy and
      Parkinson's disease and their preservation in amyotrophic lateral sclerosis.
AB  - We investigated the number of tyrosine hydroxylase (TH)-immunoreactive neurons in
      the C1 and A2 regions of the medulla, the sites of the baroreflex arc, in 7
      patients with multiple system atrophy (MSA), 8 with Parkinson's disease (PD), 9
      with amyotrophic lateral sclerosis (ALS), and 12 age-matched normal subjects to
      analyze the relationship between cardiovascular dysfunction and medullary
      catecholaminergic neurons. Orthostatic hypotension (OH) was marked in all the MSA
      patients and moderate in three PD patients. Three of the five ALS patients who
      had been on respirators showed lability of blood pressure; paroxysmal
      hypertension and nocturnal hypotension without compensatory tachycardia. All the
      MSA patients showed extremely marked decrease of TH-immunoreactive neurons in
      both the C1 and A2 regions. In the patients with Parkinson's disease, numerous TH
      immunoreactive neurons contained Lewy bodies that were immunostained by antibody
      to TH. TH-immunoreactive neurons were decreased very markedly in the A2 regions
      of two patients with OH, and three patients without OH showed fairly marked
      decreases in the C1 or A2 region. In contrast, the number of TH-immunoreactive
      neurons in ALS was the same as in normal subjects. In MSA and some PD patients,
      orthostatic hypotension may partly be due to the involvement of the medullary
      catecholaminergic neurons. The lability of blood pressure in ALS probably is not
      related to the medullary catecholaminergic neurons.

PMID- 8543952
TI  - Brain MRI correlates of cognitive impairment in primary and secondary progressive
      multiple sclerosis.
AB  - Brain magnetic resonance imaging (MRI) and an extensive battery of
      neuropsychological tests exploring frontal functions, short and long-term memory,
      visuo-spatial skills, attention and language were applied to 14 patients with
      primary progressive multiple sclerosis (PPMS) and 17 patients with secondary
      progressive MS (SPMS). Patients with PPMS and SPMS did not differ in degree of
      physical disability, but cognitive deficits were found in 9/17 (53%) patients
      with SPMS and in only 1/14 (7%) of those with PPMS (p = 0.01). Patients with SPMS
      had higher total (p = 0.004), periventricular (p = 0.008) and non-periventricular
      (p = 0.04) MRI lesion loads than patients with PPMS. In detail, patients with
      SPMS had greater involvement of frontal (p = 0.05) and occipital (p = 0.02)
      horns, trigones (p = 0.04), third ventricle (p = 0.03), basal ganglia (p = 0.02),
      parietal (p = 0.02), temporal (p = 0.004) and occipital (p = 0.03) lobes.
      Patients with SPMS and neuropsychological deficits had higher non-periventricular
      lesion loads than patients with SPMS who did not have such deficits (p = 0.005).
      Our results indicate that both neuropsychological and brain MRI abnormalities are
      more extensive in patients with SPMS. Since physical disability was similar for
      both groups, disability in PPMS may be predominantly due to spinal cord
      involvement.

PMID- 8543953
TI  - Radiation myelopathy: a clinicopathological study with special reference to
      correlation between MRI findings and neuropathology.
AB  - We describe magnetic resonance imaging (MRI) and neuropathological findings in a
      patient with chronic progressive radiation myelopathy (CPRM). An 81-year-old man
      with esophageal cancer underwent radiotherapy. Four years later he developed a
      progressive neurological deficit below the irradiated level of the spinal cord.
      Neurological examination revealed spastic paraplegia. MRI findings showed an area
      of high signal intensity on T2-weighted images of the thoracic spinal cord. On
      the basis of clinical and MRI findings, we diagnosed his condition as CPRM. MRI
      performed thirteen months after onset of neurological signs revealed mild atrophy
      of the spinal cord detected on T1-weighted images and an area of high signal
      intensity within the spinal cord detected on T2-weighted images.
      Neuropathological examination revealed findings consistent with radiation
      myelopathy. We speculate that the area of high signal intensity within the spinal
      cord detected on T2-weighted images might be a result of proliferation of small
      vessels, which was discovered upon autopsy.

PMID- 8543954
TI  - "Hyperneglect", a sequential hemispheric stroke syndrome.
AB  - We studied 8 patients with stroke and hemineglect, who presented with a transient
      active orientation and explorative behavior, turning head, eyes, and trunk in the
      opposite direction to any stimuli given in the neglected hemispace, as if
      repelled. This peculiar active behavior increased on repetitive stimulation, with
      the patient turning over by more than 180 degrees, with extreme rotation and
      opisthotonos-like extension of the axial muscles, as if looking for something
      behind him, his pillow or his bed. This behavior fluctuated during the day and
      vanished after a few days. We coined the term "hyperneglect" for this behavior,
      postulating a higher degree in the neglecting behavior or an additional field of
      hemineglect in the non neglected hemispace, or the release of repellent active
      behavior from parietal origin by the acute lesion. On CT, five patients showed
      two sequential uni- or bilateral hemispheric strokes of different ages on CT,
      while two patients had a large, unilateral infarct associated with hypertensive
      leukoencephalopathy and contralateral brain edema respectively. This behavioral
      syndrome seems to be associated with an acute stroke involving the frontal or
      parietal lobes and a previous lesion in the same or the opposite hemisphere.

PMID- 8543955
TI  - Exertional rhabdomyolysis as a result of strenuous military training.
AB  - We reviewed biochemical data from 19 soldiers who marched intermittently over 4
      weeks, carrying about 45 kg of kit, with a limited intake of food and water. The
      mean serum creatine kinase activity was higher after the march (p < 0.01),
      although the subjects did not develop symptomatic rhabdomyolysis. The mean serum
      potassium level (p < 0.005) and the mean serum sodium level (p < 0.05) were lower
      after the march. The level of serum osmolality showed no significant changes.
      Subclinical rhabdomyolysis was not rare among the soldiers. We also report a case
      of the soldier with exertional clinical rhabdomyolysis.

PMID- 8543956
TI  - Experimental neonatal autoimmune myasthenia gravis: an immunohistochemical,
      ultrastructural and electrophysiological study of the motor end-plate.
AB  - Neonatal rats born of and nursed by mothers immunized with Narke japonica
      acetylcholine receptor protein had elevated serum anti-acetylcholine receptor
      antibodies that reached the mother's level on day 10 after delivery and decreased
      rapidly after weaning. IgG was present at the motor end-plates up to day 170, and
      the motor end-plate fine structure remained abnormal up to day 80. Miniature end
      plate potential amplitudes in the diaphragm were at the control levels within 10
      days of birth, but were lower than those of the controls up to day 80 after
      birth. We could not obtain the direct evidence that transient synthesis of
      antibodies occurs in experimental autoimmune myasthenia gravis pups. This model
      can serve as an experimental model of transient neonatal myasthenia gravis in
      humans, exception for the route of antibody transfer and the time of the onset of
      illness.

PMID- 8543957
TI  - Epidemiology of potential association between L-tryptophan ingestion and
      eosinophilia-myalgia syndrome.
AB  - This article examines the methodology of the epidemiological studies of the
      association between L-tryptophan and eosinophilia-myalgia syndrome (EMS) and
      evaluates the validity of the conclusions from these studies. In the initial case
      control studies of L-tryptophantryptophan and EMS there were a variety of
      methodological problems, including different sources and different exclusion
      criteria for cases and controls, which could have resulted in selection bias, as
      well as problems with information bias and confounding. The studies of
      manufacturer and brand also had similar potential for bias. The L-tryptophan-EMS
      association is based on two small studies that had important methodological
      inadequacies. Subsequent studies of brand of L-tryptophan also contained errors
      in design, which may have produced biased results and call the conclusions into
      question. The cause of eosinophilia-myalgia syndrome remains unknown.

PMID- 8543958
TI  - Computerised record linkage: compared with traditional patient follow-up methods
      in clinical trials and illustrated in a prospective epidemiological study. The
      West of Scotland Coronary Prevention Study Group.
AB  - Computerised record linkage systems have great potential for enhancing or even
      replacing traditional methods of adverse event reporting based on active patient
      follow-up, both in clinical trials and in epidemiological studies. However, these
      methods must be evaluated. The West of Scotland Coronary Prevention Study
      (WOSCOPS) is a randomised double-blind clinical trial of pravastatin versus
      placebo in the primary prevention of coronary heart disease, with coronary heart
      disease death plus nonfatal myocardial infarction as its primary end point.
      Adverse event reporting is based on active patient follow-up at routine trial
      visits. In parallel with this approach, we have obtained computer records of all
      deaths, incident cancers, and hospitalisations for our subjects by linking their
      names, dates of birth, and postcodes of their home addresses with a Scottish
      national database operated by the Scottish Record Linkage system. The results of
      this comparative study, based on follow-up of the 6595 men ages 45-64 randomised
      in WOSCOPS, demonstrate minor flaws in both systems, show that follow-up based on
      computerised linkage alone can be as effective as reporting based on direct
      contact with the patients, and show that a system based on both approaches
      provides a direct cross-validation of the two approaches to adverse event
      reporting while minimising the frequency of unreported events. Preliminary
      results are reported for a prospective epidemiological study of 80,184 men, ages
      45-64 years, who were screened for coronary heart disease risk factors as part of
      WOSCOPS. This study is based solely on computerised linkage reporting of events
      on these subjects. This provides an indication of the number of events in various
      categories that will be available for analysis in future reports. The
      associations between death rates and standard risk factors such as age, blood
      pressure, total cholesterol level, and smoking status mirror those reported in
      other studies.

PMID- 8543959
TI  - Randomized clinical trial of ascorbic acid in the treatment of pressure ulcers.
AB  - The objective of this study was to assess the effects of ascorbic acid
      supplementation, 500 mg twice daily in the treatment of pressure ulcers as an
      adjunct to standardized treatment. The design consisted of a multicenter blinded
      randomized trial. The control group received 10 mg of ascorbic acid twice daily.
      Patients from 11 nursing homes and 1 hospital participated. Main outcome measures
      included wound survival, healing rates of wound surfaces, and clinimetric changes
      over 12 weeks. Eighty-eight patients were randomized. Intention-to-treat analysis
      showed that the wound closure probability per unit time (i.e., the closure rate)
      was not higher in the intervention group than in the control group (Cox hazard
      ratio of 0.78 [90% precision interval, 0.44-1.39]). Mean absolute healing rates
      were 0.21 and 0.27 cm2/week in the intervention and control group, respectively
      (PI of the adjusted difference: -0.17 to 0.13). Relative healing rates and
      healing velocities did not show favorable results of ascorbic acid
      supplementation, either. A panel scored slides of the ulcers with a report mark
      between 1 (bad) and 10 (excellent). The improvement was 0.45 and 0.72 points per
      week in the intervention and control group, respectively (PI of the adjusted
      difference: -0.50 to 0.20). With another clinimetric index we could not show any
      differences, either. These data do not support the idea that ascorbic acid
      supplementation (500 vs. 10 mg twice daily) speeds up the healing of pressure
      ulcers.

PMID- 8543960
TI  - Optimal survey design for community intervention evaluations: cohort or cross
      sectional?
AB  - Community intervention evaluations that measure changes over time may conduct
      repeated cross-sectional surveys, follow a cohort of residents over time, or
      (often) use both designs. Each survey design has implications for precision and
      cost. To explore these issues, we assume that two waves of surveys are conducted,
      and that the goal is to estimate change in behavior for people who reside in the
      community at both times. Cohort designs are shown to provide more accurate
      estimates (in the sense of lower mean squared error) than cross-sectional
      estimates if (1) there is strong correlation over time in an individual's
      behavior at time 0 and time 1, (2) relatively few subjects are lost to followup,
      (3) the bias is relatively small, and (4) the available sample size is not too
      large. Otherwise, a repeated cross-sectional design is more efficient. We
      developed methods for choosing between the two designs, and applied them to
      actual survey data. Owing to drop-outs and losses to followup, the cohort
      estimates were usually more biased than the cross-sectional estimates. The
      correlations over time for most of the variables studied were also high. In many
      instances the cohort estimate, although biased, is preferred to the relatively
      unbiased cross-sectional estimate because the mean squared error was smaller for
      the cohort than for the cross-sectional estimate. If these results are replicated
      in other data, they may result in guidelines for choosing a more efficient study
      design.

PMID- 8543961
TI  - Self-administered examination versus conventional medical examination of the
      musculoskeletal system in the neck, shoulders, and upper limbs. The Stockholm
      MUSIC I Study Group.
AB  - A self-administered examination protocol of the musculoskeletal system in the
      neck, shoulders, and upper limbs was mailed to 350 subjects and the results were
      compared to those of a subsequent medical examination. The prevalences of
      reported positive findings were higher than in the medical examination. Validity
      ranged between poor and good. Acceptable validity was noted for items measuring
      tenderness. No systematic substantial exposure-related misclassification was
      noted. Self-administered examination of the musculoskeletal system is not
      suitable to replace a traditional medical examination in epidemiological studies.
      Self-administered examination of tenderness could, however, be used as a
      screening method in analytical studies of relations between exposure and
      disorders in the musculoskeletal system. Subjects reporting such findings at a
      self-administered examination could be further examined by professional examiners
      for definite diagnostic appraisal. Substantial savings in medical examination
      resources could thereby be obtained.

PMID- 8543962
TI  - Ten-year changes in the obesity, abdominal adiposity, and serum lipoprotein
      cholesterol measures of Western Samoan men.
AB  - Previously reported associations between abdominal adiposity and coronary heart
      disease (CHD) may be mediated through serum lipids. In the present longitudinal
      study, 43 Western Samoan men who participated in a 1982 study were recontacted
      for a second determination of anthropometric and serum lipoprotein cholesterol
      levels. The men showed dramatic increases in weight (mean change +/- SD: 10.5 +/-
      8.8 kg), abdominal circumference (10.0 +/- 7.6 cm), total cholesterol (49.5 +/-
      26.4 mg/dl), and non-HDL cholesterol (53.1 +/- 26.6 mg/dl). A new indicator was
      used to estimate changes in abdominal adiposity: the residual from the regression
      of change in the abdominal circumference on change in body weight (the AR). The
      AR was significantly correlated with changes in total (r = 0.38) and non-HDL
      cholesterol (r = 0.39). Changes in HDL cholesterol were correlated with changes
      in weight only (r = -0.37). These bivariate relations remained significant in
      multiple linear regression analyses. These longitudinal results are the first to
      suggest changes in abdominal adiposity are related to changes in total and non
      HDL cholesterol levels.

PMID- 8543963
TI  - Importance of events per independent variable in proportional hazards analysis.
      I. Background, goals, and general strategy.
AB  - Multivariable methods of analysis can yield problematic results if methodological
      guidelines and mathematical assumptions are ignored. A problem arising from a too
      small ratio of events per variable (EPV) can affect the accuracy and precision of
      regression coefficients and their tests of statistical significance. The problem
      occurs when a proportional hazards analysis contains too few "failure" events
      (e.g., deaths) in relation to the number of included independent variables. In
      the current research, the impact of EPV was assessed for results of proportional
      hazards analysis done with Monte Carlo simulations in an empirical data set of
      673 subjects enrolled in a multicenter trial of coronary artery bypass surgery.
      The research is presented in two parts: Part I describes the data set and
      strategy used for the analyses, including the Monte Carlo simulation studies done
      to determine and compare the impact of various values of EPV in proportional
      hazards analytical results. Part II compares the output of regression models
      obtained from the simulations, and discusses the implication of the findings.

PMID- 8543964
TI  - Importance of events per independent variable in proportional hazards regression
      analysis. II. Accuracy and precision of regression estimates.
AB  - The analytical effect of the number of events per variable (EPV) in a
      proportional hazards regression analysis was evaluated using Monte Carlo
      simulation techniques for data from a randomized trial containing 673 patients
      and 252 deaths, in which seven predictor variables had an original significance
      level of p < 0.10. The 252 deaths and 7 variables correspond to 36 events per
      variable analyzed in the full data set. Five hundred simulated analyses were
      conducted for these seven variables at EPVs of 2, 5, 10, 15, 20, and 25. For each
      simulation, a random exponential survival time was generated for each of the 673
      patients, and the simulated results were compared with their original
      counterparts. As EPV decreased, the regression coefficients became more biased
      relative to the true value; the 90% confidence limits about the simulated values
      did not have a coverage of 90% for the original value; large sample properties
      did not hold for variance estimates from the proportional hazards model, and the
      Z statistics used to test the significance of the regression coefficients lost
      validity under the null hypothesis. Although a single boundary level for avoiding
      problems is not easy to choose, the value of EPV = 10 seems most prudent. Below
      this value for EPV, the results of proportional hazards regression analyses
      should be interpreted with caution because the statistical model may not be
      valid.

PMID- 8543965
TI  - A multinational case-control study of cardiovascular disease and steroid hormone
      contraceptives. Description and validation of methods. World Health Organization
      Collaborative Study of Cardiovascular and Steroid Hormone Contraception.
AB  - A hospital-based, case-control study of the association between current usage of
      oral contraceptives and first-time cases of acute myocardial infarction, stroke,
      or a venous thromboembolic event (deep vein thrombosis or pulmonary embolus) was
      carried out in 17 countries from four regions (Africa, Asia, Europe, and Latin
      America). A total of 3792 cases and 10,281 hospitalised controls matched for age
      were recruited during a 4-year period, ending in June 1993. The study was
      designed to have sufficient power to detect a relative risk of 2 for developing
      each of the three study diseases, associated with current oral contraceptive use
      in each of the four regions, with the exception of acute myocardial infarction
      (for which all non-European regions were to be combined) and for venous
      thromboembolic events in Asia, where these disorders are rare. This report
      describes the background, pilot study, methods, and the analyses carried out to
      validate the methods used in the study.

PMID- 8543966
TI  - Lack of NF1 expression in a sporadic schwannoma from a patient without
      neurofibromatosis.
AB  - The neurofibromatosis type 1 (NF1) gene encodes a tumor suppressor protein,
      neurofibromin, which is expressed at high levels in Schwann cells and other adult
      tissues. Loss of NF1 expression has been reported in Schwann cell tumors
      (neurofibrosarcomas) from patients with NF1 and its loss is associated with
      increased proliferation of these cells. In this report, we describe
      downregulation of NF1 expression in a single spinal schwannoma from an individual
      without clinical features of neurofibromatosis type 1 or 2. Barely detectable
      expression of NF1 RNA was found in this tumor by in situ hybridization using an
      NF1-specific riboprobe as well as by Northern blot and reverse-transcribed (RT)
      PCR analysis. In Schwann cells cultured from this schwannoma, abundant expression
      of NF1 RNA could be detected by Northern blot and RT-PCR analysis. These results
      suggest that, in some tumors, expression of NF1 may be downregulated by factors
      produced within the tumor and may represent a novel mechanism for inactivating
      these growth suppressing genes and allowing for increased cell proliferation in
      tumors.

PMID- 8543967
TI  - Correlation of relaxometry and histopathology: the transplantable human
      glioblastoma SF295 grown in athymic nude mice.
AB  - Human glioblastomas of the brain are characterized by a wide range of proton
      relaxation rates in vitro (1/T1 and 1/T2) and heterogeneous appearance in
      magnetic resonance imaging. It was previously found that their 1/T1 values vary
      widely at magnetic field strengths much below imaging fields, even at the same
      water content. In the present study, we measure 1/T1 at different magnetic field
      strengths (NMRD profile) for a specific transplantable, human glioblastoma
      (SF295), grown subcutaneously in athymic nude mice, to search for histologic
      characteristics that might correlate with the variability of 1/T1 at low fields
      (1/T1L). Using a field-cycling relaxometer, NMRD profiles were obtained for 32
      fresh, histologically characterized, tumor specimens, 7 to 24 days post
      implantation of cryopreserved SF295 fragments. Tumor volume, dry weight, and pH
      of specimens were determined, the extent of hemorrhage and necrosis rated, and
      specimen location within the tumor recorded. A statistically significant increase
      in the average 1/T1 was found with increasing level of necrosis at 0.0024 T and
      below, possibly reflecting progressive protein aggregation in samples with up to
      40% necrosis. This correlation was not significant at imaging fields. Although pH
      was increased in central necrosis, neither pH, dry weight, sample location, nor
      fresh hemorrhage could explain the changes in 1/T1L. The variability of 1/T1L
      among SF295 samples is much reduced compared to that of fresh surgical specimens
      of human glioblastomas of the brain. The heterogeneous appearance of
      glioblastomas in MRI may have a histologic correlate which reflects molecular
      changes involved with induction of cell death and necrosis. Further
      investigations may identify the factors responsible for affecting 1/T1L (hypoxia,
      radiation, chemotherapy).

PMID- 8543968
TI  - Effect of hyperthermia on cyclin B expression in a human glioblastoma cell line.
AB  - Effects of hyperthermia on the cell kinetics of glioblastoma cells were
      investigated using flow cytometry. Pulse-labeling with 5-bromodeoxyuridine (BUdR)
      and chasing of the labeled cells revealed temporary accumulation of the labeled
      cells in G2M phase and a reduction of DNA synthesis. The level of cyclin B rises
      rapidly in G2 phase and falls at the end of mitosis in normal cycling cells.
      Cyclin B binds to p34cdc2, resulting in histone kinase activity which is
      necessary for the initiation of mitosis. The amount of p34cdc2 remains constant
      throughout the cell cycle. The level of cyclin B was measured using an anti
      cyclin B antibody and flow cytometry in order to investigate the cause of the G2
      accumulation induced by hyperthermia. A low level of cyclin B, in comparison with
      that of normal cycling cells, persisted for more than 3 h after hyperthermia.
      These results indicate that the temporary accumulation of cells in G2M phase
      after hyperthermia may be caused, at least in part, by an insufficient level of
      cyclin B.

PMID- 8543969
TI  - Spinal 111Indium-DTPA CSF flow studies in leptomeningeal metastasis.
AB  - Sixteen consecutive patients (8 men; 8 women; age range 6-63 years, median 40
      years) with leptomeningeal metastasis were found by radionuclide ventriculography
      to have cerebrospinal fluid (CSF) flow interruption at the following sites:
      cisterna magna/basal cisterns (6); cervical (5) and thoracic (3) spinal
      subarachnoid space. Two additional patients had no evidence of interruption of
      CSF flow. All patients underwent intralumbar injection of 111Indium-DTPA and
      imaging of spinal ascent of radionuclide, corroborating sites of CSF flow
      disruption seen by radionuclide ventriculography. Median (range) time to
      appearance in lumbar, thoracic and cervical spinal subarachnoid compartments were
      1 (1), 22.5 (20-25) and 32.5 (30-35) minutes respectively. Appearance of
      radionuclide in the cisterna magna/basal cisterns, sylvian cisterns, ventricular
      system and high cerebral convexity was 37.5 (35-40), 65 (60-70), 1440 (1440) and
      1440 (1440) minutes respectively. Only 1 of 8 patients with interruption of CSF
      flow within the spinal subarachnoid space shown by intralumbar radionuclide flow
      study, was seen by either CT myelography or contrast enhanced spine MR to have
      CSF flow block. No patient with base of brain block (0/6) shown by radionuclide
      CSF flow studies demonstrated CSF flow disruption by either cranial contrast
      enhanced CT or MR. In conclusion, spinal 111In-DTPA CSF flow studies confirmed
      sites of CSF flow block shown by radionuclide ventriculography and demonstrate
      the feasibility of assessing CSF compartmentalization by intralumbar radionuclide
      administration. Furthermore, radionuclide CSF flow studies when compared to
      conventional neuroradiographic imaging are more sensitive in demonstrating
      interruption of CSF flow.

PMID- 8543970
TI  - Results of a randomized trial comparing intra-arterial cisplatin and intravenous
      PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative
      Group trial 8420A.
AB  - PURPOSE: To test the efficacy of intra-arterial (IA) cisplatin versus intravenous
      (IV) PCNU for treating primary brain tumors, in a randomized trial (Brain Tumor
      Cooperative Group [BTCG] Trial 8420A). METHODS: 311 adult patients (ages 19-79
      years; median 45) with supratentorial tumors (confirmed histologically) were
      randomized by nine participating institutions. Patients were required to have
      completed radiotherapy (4500-6020 cGy to the tumor bed) before randomization.
      Patients were stratified as either nonprogressive (clinically and radiologically
      stable) or progressive. Results were analyzed for the 311 patients in the
      randomized population (RP), and for the 281 patients in the Valid Study Group
      (VSG) meeting protocol eligibility requirements. 56% of patients in the VSG had
      glioblastoma multiforme, 33% had other malignant glioma, and 11% had low-grade
      glioma. 64% were stratified as progressive. 12% had received prior chemotherapy.
      RESULTS: The group randomized to PCNU had the longer survival (p = 0.06 for the
      RP, p = 0.07 for the VSG). In the VSG, median survival was 10 months for the
      cisplatin group, 13 months for the PCNU group. The difference between treatment
      groups was significant (p < or = 0.02) when adjusted for important prognostic
      factors. PCNU lead to greater hematotoxicity; cisplatin lead to greater renal
      toxicity and some ototoxicity. Some cisplatin patients experienced complications
      associated with IA administration, including six cases of encephalopathy.
      CONCLUSION: The trial showed a survival advantage to the group randomized to
      PCNU, although the difference was modest. Coupled with previous BTCG results,
      these trails suggest that PCNU is an active drug for brain tumors.

PMID- 8543971
TI  - Sacrococcygeal chordoma metastatic to the brain with review of the literature.
AB  - A 29-year-old man presented with headache, confusion, word-finding difficulty,
      and a visual field deficit 16 months after complete removal of a sacrococcygeal
      chordoma. Magnetic resonance imaging of the head demonstrated two discrete
      enhancing left occipital lesions with associated cerebral edema. Both masses were
      surgically excised and their histological appearance was consistent with
      chordoma. Chordoma from the sacral region is known to metastasize to the lungs
      and the vertebral bodies but has rarely been shown to spread to the brain.
      Dissemination to the brain in this case may be related to the extent of the
      metastatic pulmonary disease and the anaplastic appearance of the primary tumor.

PMID- 8543972
TI  - Successful treatment for solitary brain metastasis from alveolar soft part
      sarcoma.
AB  - Following pulmonary metastases, alveolar soft part sarcoma has an unexplained
      predisposition to metastasize to the brain. Herein, a case of alveolar soft part
      sarcoma solitarily metastatic to the brain is described. A 23-year old female
      underwent the resection of alveolar soft part sarcoma from the right thigh. Three
      years after the surgery, a brain tumor was resected and pathology proved it was a
      metastatic alveolar soft part sarcoma. She is currently alive and well 6 years
      after brain surgery. Our report suggests that surgical resection for solitary
      brain metastasis from alveolar soft part sarcoma is an effective treatment
      modality.

PMID- 8543973
TI  - Polyamines in brain tumor therapy.
AB  - In the search for ways to augment current brain tumor therapies many have sought
      to exploit the fact that adult brain tissue is virtually lacking in cell
      division. This endorses a special appeal to therapeutic approaches which target
      the dependence on cell division for brain tumor growth. Polyamines play an
      essential role in the proliferation of mammalian cells and depletion results in
      inhibition of growth. As a result, there are investigations into the feasibility
      of controlling tumor growth by targeting the enzymes in polyamine metabolism with
      specific enzyme inhibitors. DFMO, an inhibitor of putrescine synthesis, is a
      cytostatic agent which in combination with tritiated radioemitters or cytotoxic
      agents such as, MGBG or BCNU is an effective antitumor agent, but the
      effectiveness of DFMO in vivo is reduced by tumor cell uptake of polyamines
      released into the circulation by normal cells and from gut flora or dietary
      sources. However, DFMO therapy combined with elimination of exogenous polyamines
      inhibits tumor growth but also results in body weight loss, reduced protein
      synthesis and evidence of toxicity. Furthermore, tumor growth recurs upon
      termination of treatment. In contrast, competitive polyamine analogs function in
      the homeostatic regulation of polyamine synthesis but fail to fulfill the
      requirements for growth and they continue to inhibit tumor growth for several
      weeks after cessation of treatment. Analogs are now in clinical trials. However,
      their action may be highly specific and differ from one cell type to another. We
      suggest that the effectiveness of polyamine based therapy would be enhanced by
      two approaches: local delivery by intracerebral microdialysis and tumor cell
      killing by internal radioemitters such as tritiated putrescine or tritiated
      thymidine which are taken up in increased amounts by polyamine depleted tumor
      cells. The growth inhibition by polyamine depletion prevents the dilution of the
      radioactive putrescine and thymidine. The overload of radioactivity kills the
      growth inhibited cells so that growth cannot recur when treatment terminates.

PMID- 8543974
TI  - Leukotriene E4 selectively increase the delivery of methotrexate to the C6
      gliomas in rats.
AB  - Leukotriene E4 (LTE4) infused into the carotid artery ipsilateral to an
      experimental glial tumor will selectively increase the blood-tumor permeability
      within the tumor. In this study the effects of intracarotid infusion of LTE4 on
      blood-tumor barrier (BTB) permeability for intravenously administered 14C
      aminoisobutyric acid, 14C-5-fluorouracil (5-FU) 14C-sucrose and 3H-methotrexate
      (MTX) were examined in C6 gliomas of rats. The intracarotic administration of
      LTE4 selectively opened the BTB, without affecting permeability of normal brain
      tissue, to all of the above tracers. Intracarotid infusion of LTE4 had the
      tendency to increase the uptake of intravenously administered 5-FU within the
      tumor, but this effect was not statistically significant. The intracarotid
      infusion of LTE4, however, increased the uptake of intravenously injected MTX
      about twofolds within the tumor (Ki = 19.48 +/- 1.06 vs 10.12 +/- 1.19, p < 0.01)
      without increasing the uptake in the normal brain tissue.

PMID- 8543975
TI  - Endocrine functions in long-term survivors of low-grade supratentorial glioma
      treated with radiation therapy.
AB  - Endocrine functions were studied in long-term survivors of low-grade glioma
      treated with radiotherapy. Hypothalamic-pituitary dysfunction has recently been
      reported to occur more frequently than generally considered. Because endocrine
      dysfunction is a treatable condition, careful testing and, if necessary,
      supplementary treatment may enhance quality of life. Thirteen adult patients
      treated with radiotherapy because of supratentorial low-grade glioma at least one
      year before (range 1-11.5 years) were tested. Focal brain radiotherapy (45-61.2
      Gy), with calculated dose to the hypothalamic-pituitary area ranging from 0 to 50
      Gy (mean 36.1) had been applied to all patients. Serum levels of pituitary
      hormones, cortisol and thyroid hormone were determined before and after
      stimulation with hypothalamic hormones. In 10 out of 13 patients one or more
      hormonal values were out of the normal range. Most disturbances were demonstrated
      in the pituitary-adrenal axis (8 patients) and the GH-axis (4 patients). None of
      the patients had clinical symptomatology of adrenal, thyroid or gonadal
      dysfunction. Careful endocrine testing after cranial radiotherapy may reveal
      (subclinical) hypothalamic-pituitary dysfunction in long-term survivors. Follow
      up testing in these patients seems warranted.

PMID- 8543976
TI  - Maladaptation of vascular response in frontal area of patients with orthostatic
      hypotension.
AB  - To clarify the relationship between abnormalities in cerebral blood flow (CBF)
      and in blood pressure regulation, we performed 99mTc-HMPAO brain SPECT in
      association with measurement of plasma norepinephrine and blood pressure in both
      the upright and supine positions. METHODS: We studied six patients with
      orthostatic hypotension and six normal patients. No patient had any significant
      stenosis of the carotid arteries on echocardiography-Doppler ultrasound and no
      abnormalities on brain MRI or CT. Changes in systolic blood pressure were
      monitored during the upright test, and 8-ml blood samples were taken at baseline
      and at 1 and 5 min after the upright position. RESULTS: Systolic blood pressure
      decreased by a mean of 38 +/- 10 and 9 +/- 3 mmHg in the orthostatic hypotension
      and normal groups, respectively. Compared with baseline values, plasma
      norepinephrine levels at 1 and 5 min after the upright test did not increase in
      the orthostatic hypotension group but did increase significantly in the normal
      group. In the orthostatic hypotension group, 99mTc-HMPAO brain SPECT showed
      postural cerebral hypoperfusion in the bilateral frontal areas, of which the mean
      count ratio of the frontal-to-cerebellar area between the upright and supine
      positions significantly changed from 0.871 +/- 0.029 to 0.942 +/- 0.067 and from
      0.881 +/- 0.035 to 0.954 +/- 0.073 in the right and left areas, respectively. No
      postural change in CBF was evident in other areas in the orthostatic hypotension
      group. In the normal group, there were no such changes in CBF, blood pressure and
      plasma norepinephrine levels during the upright test. CONCLUSION: Postural
      cerebral hypoperfusion in the frontal areas in the orthostatic hypotension group
      might relate to maladaptation of the vascular response during the upright test.

PMID- 8543977
TI  - Targeted delivery of antineoplastic agent to bone: biodistribution studies of
      technetium-99m-labeled gem-bisphosphonate conjugate of methotrexate.
AB  - A methotrexate-bisphosphonate conjugate containing a peptide bond has been found
      to possess over five times greater antineoplastic activity against osteosarcoma
      in experimental animal models compared with methotrexate alone. METHODS: The
      conjugate was labeled with 99mTc in the presence of stannous ions to determine
      biologic distribution, with special reference to osseous tissue. Biodistribution
      studies were carried out in mice after intravenous administration of the labeled
      conjugate. Radionuclide imaging of rabbits was also performed. RESULTS: The
      labeled conjugate behaved like a bone-seeking agent. CONCLUSION: The present
      study indicates that the concept of treating osteosarcoma or metastatic tumors of
      bone with this class of agents has a firm basis.

PMID- 8543978
TI  - In vitro and in vivo studies of substance P receptor expression in rats with the
      new analog [indium-111-DTPA-Arg1]substance P.
AB  - We evaluated the potential usefulness of a new radiolabeled substance P (SP)
      analog, [111In-DTPA-Arg1]SP, as a radiopharmaceutical for the in vivo detection
      of SP receptor-positive (SPR+) immunologic disorders (i.e., inflammatory bowel
      disease and arthritis) and tumors (i.e., carcinoid). METHODS: Substance P, [DTPA
      Arg1]SP and [3-(p-hydroxyphenyl)propionyl-Arg1]SP (Bolton-Hunter-SP, [BH-SP])
      were tested as competitors for 125I-BH-SP to SPR in rat brain cortex membranes.
      An autoradiographic displacement study of the submandibular gland of the rat with
      the 125I-BH-SP as radioligand and [DTPA-Arg1]SP as competitor was performed.
      Tissue distribution and ex vivo autoradiography were studied in rats, with and
      without pretreatment with the selective nonpeptide antagonist CP96,345 to
      quantify specific binding. In vivo metabolism of [111In-DTPA-Arg1]SP was
      performed in control rats. Gamma-camera scintigraphic studies were carried out
      with control rats to visualize the SPR+ salivary glands in rats bearing the SPR+
      transplantable pancreatic tumor CA20948 and in rats with SPR+ adjuvant arthritic
      joints, which was induced after injection of a homogenate of Mycobacterium
      tuberculosis. RESULTS: Substance P, [DTPA-Arg1]SP and BH-SP dose-dependently
      inhibited binding of 125I-BH-SP to SPR in rat brain cortex membranes with IC50
      values of 0.2, 4 and 2 nM, respectively. In an autoradiographic displacement
      study of the submandibular gland with 125I-BH-SP as radioligand, an IC50 of 2.7
      nM was found for [DTPA-Arg1]SP. In vivo metabolism of the radiopharmaceutical in
      the rat revealed a renal clearance rate of 50% of the injected radioactive dose
      in 30 min and a rapid enzymatic degradation of the radiopharmaceutical, resulting
      in an effective half-life of the intact radiopharmaceutical in blood of
      approximately 3 min. Tissue distribution and ex vivo autoradiographic studies in
      rats showed uptake and specific binding of radioactivity in isolated tumors and
      submandibular and parotid glands. Optimum SPR+ target-to-background ratios were
      found 24 hr after injection of [111In-DTPA-Arg1]SP. Visualization of normal SPR+
      tissues, such as the salivary glands by gamma camera scintigraphy, after
      administration of [111In-DTPA-Arg1]SP was demonstrated in untreated rats.
      Pathological SPR+ processes were visualized both in rats bearing the
      transplantable pancreatic tumor CA20948 and in those with adjuvant mycobacteria
      tuberculosis-induced arthritic joints. CONCLUSION: [Indium-111-DTPA-Arg1]SP can
      be used successfully to visualize SPR+ processes in vivo by gamma camera
      scintigraphy.

PMID- 8543979
TI  - Continuous intravenous infusion of iodine-123-IBZM for SPECT determination of
      human brain dopamine receptor occupancy by antipsychotic agent RWJ-37796.
AB  - PET has shown that dose-dependent in vivo occupancy of dopamine receptors by
      antipsychotic drugs is associated with clinical response to antipsychotic agents
      and the production of extrapyramidal side effects. We studied the feasibility of
      administering [123I]IBZM as a bolus plus continuous infusion over 8 hr to achieve
      unchanging regional brain activity levels, and the application of [123I]IBZM
      continuous infusion to examine the effects of the antipsychotic agent RWJ-37796,
      on striatal activity in humans. METHODS: Five healthy male subjects received a
      bolus of [123I]IBZM followed by a continuous infusion at a bolus (mCi):infusion
      (mCi/hr) ratio of 6:1. Serial SPECT images were obtained every 2-3 min for a
      total of 8 hr with a 1-2 hr break in the scanning session. Serial venous blood
      samples were obtained every 30 min for the duration of the study. All five
      subjects achieved unchanging plasma [123I]IBZM and striatal brain-activity levels
      over the 300-420 min postinitiation of tracer infusion. Two subjects achieved
      flat brain time-activity curves later than the others, suggesting the bolus-to
      infusion ratio was slightly high. An additional six healthy male subjects
      received a similar bolus plus constant infusion of [123I]IBZM. RWJ-37796 (0.04
      mg/kg) was administered intravenously 157 +/- 13.7 min after the initiation of
      [123I]IBZM infusion. Serial SPECT brain images, serum prolactin and
      extrapyramidal side effect ratings were obtained for an additional 330 min.
      RESULTS: All six subjects demonstrated rapid and marked reduction of striatal
      activity following RWJ-37796 without return of striatal activity to baseline
      levels over the 5.5 hr of continued [123I]IBZM administration. Estimated receptor
      occupancy by RWJ-37796 was 57% +/- 5% (range 47%-67%). Prolactin was only
      transiently increased in all subjects by 1054% +/- 1084% over baseline. One
      subject experienced moderate extrapyramidal symptoms (akasthisia) during RWJ
      37796 injection. CONCLUSION: SPECT imaging during continuous [123I]IBZM infusion
      provides a powerful within-scan method for determining both temporal binding
      characteristics and receptor occupancy of striatal dopamine receptors by
      antipsychotic agents.

PMID- 8543980
TI  - Concept of reaction volume in the in vivo ligand-receptor model.
AB  - In vivo quantification of receptor concentration and ligand affinity using data
      obtained with PET is based on the compartmental analysis of ligand-receptor
      interactions. There is, however, an inconsistency between the assumed homogeneity
      of the ligand concentration in each compartment, a basic hypothesis of the
      compartmental analysis, and the obvious heterogeneity of the tissue. Our goal was
      to study the effects of the free ligand concentration heterogeneity on the
      parameters describing in vivo binding reaction and to introduce the concept of
      reaction volume, VR, to account for that heterogeneity. METHODS: The reaction
      volume is defined as the volume in which the free ligand mass present in 1 ml of
      tissue would have uniformly distributed with the same concentration as that in
      the vicinity of the receptor sites. The consequence of the heterogeneity of the
      free ligand concentration is that the equilibrium dissociation rate constant
      estimated from PET data corresponds to KdVR and not to Kd alone (defined by the
      ratio of the dissociation over the association rate constants). As a consequence,
      it is proposed to estimate the reaction volume as the ratio between the
      equilibrium dissociation constants obtained from in vivo and in vitro data (KdVR
      and Kd, respectively). RESULTS: We used data obtained from studies performed with
      eight different molecules and found a correlation between the reaction volume and
      the molecule lipophilicity. This correlation can be used as a method to estimate
      the order of magnitude of VR from the lipophilicity which is easily accessible
      experimentally. CONCLUSION: Reaction volume is an important parameter in in vivo
      ligand-receptor interaction modeling.

PMID- 8543981
TI  - Compartments and reaction volumes of brain fluid spaces: shaken, not stirred.

PMID- 8543982
TI  - Validation of postinjection transmission measurements for attenuation correction
      in neurological FDG-PET studies.
AB  - Accurate estimation of local cerebral metabolic rate of glucose utilization
      (LCMRGlu) with PET requires a separate measurement of photon attenuation using a
      transmission source that extends study duration. The feasibility of postinjection
      transmission, (PIT) scanning has been demonstrated but not previously validated
      in humans. METHODS: Preinjection and postinjection transmission scans were
      performed in 26 patients undergoing routine [18F]fluorodeoxyglucose (FDG)
      neurological PET. The PIT data were processed with two methods: One estimated
      emission contamination using an independent emission scan (PITind); the other
      estimated the contamination directly from the PIT scan, using simultaneously
      acquired emission data for subtraction (PITsim). These methods were compared with
      measured attenuation correction (AC) using preinjection transmission data (ACpre)
      and calculated AC (ACcalc). After reconstruction, image data were reformatted to
      fit a standard brain atlas to facilitate analysis of the region of interest and
      to allow subtraction of datasets averaged over all subjects. RESULTS: The ratios
      of LCMRGlu values with respect to those obtained by the ACpre method ranged from
      0.98 to 1.06 (mean +/- s.d., 1.01 +/- 0.02) for PITind, from 0.96 to 1.04 (mean
      0.99 +/- 0.02) for PITsim and from 0.77 to 1.12 (mean 0.96 +/- 0.07) for ACcalc.
      Both PIT methods agreed well with the ACpre method, whereas ACcalc gave rise to
      appreciable bias in structures near thick bone or sinuses. CONCLUSION: Accurate
      quantitative estimates of LCMRGlu can be obtained using PIT measurements. The PIT
      methods shorten study duration and increase patient throughput. The PITsim method
      has the further advantage that it is not affected by tracer redistribution and
      can therefore be applied to tracers with relatively rapid kinetics in vivo.

PMID- 8543983
TI  - Automated interstudy image registration technique for SPECT and PET.
AB  - We report the extended application of an automated computer technique for three
      dimensional spatial registration of SPECT and PET studies. METHODS: The technique
      iteratively reslices a misaligned data set until the sum of the absolute
      differences (SAD) from a reference data set is minimized. The registration
      accuracy was assessed in Hoffman brain phantom studies collected with known
      misalignments and transmission studies of a thorax phantom with fiducial markers.
      The SAD was compared with three other cost functions: stochastic sign change
      criterion, sum of products and standard deviation (s.d.) of ratios. In clinical
      neurological and myocardial perfusion studies, registration accuracy was
      estimated from the relative locations of landmarks in the reference and
      registered data sets. RESULTS: Registration accuracy in the Hoffman brain phantom
      studies was -0.07 +/- 0.46 mm (mean +/- s.d.) for translations and -0.01 +/- 0.20
      degrees for rotations, with maximum translation and rotation errors of 1.2 mm and
      0.8 degree, respectively. The SAD was the most accurate and reliable cost
      function. Registration errors in the thorax phantom were 3.1 +/- 1.7 mm. Mean
      accuracy in the neurological studies, estimated from landmark pairs, was 2.0 +/-
      1.1 mm for SPECT to SPECT and 1.8 +/- 1.1 mm for PET to SPECT registrations.
      Average registration accuracy in 201Tl myocardial perfusion studies was 2.1 +/-
      1.2 mm. CONCLUSION: Our registration method (a) provided accurate registrations
      for phantom and clinical SPECT and PET studies, (b) is fully automated, (c)
      simplifies comparison of data sets obtained at different times and with different
      modalities, and (d) can be applied retrospectively.

PMID- 8543984
TI  - Dosimetric evaluation of copper-64 in copper-67-2IT-BAT-Lym-1 for
      radioimmunotherapy.
AB  - Copper-67 (67Cu) is an attractive radionuclide for radioimmuno-therapy because of
      its favorable physical and biologic characteristics. Current supplies of 67Cu,
      however, contain as much as 60% of 64Cu at the time of delivery. Scatter photons
      from 64Cu enter the 67Cu energy window, affecting image resolution and counting
      accuracy. The radiation dose to tissue is also altered. METHODS: A line source
      and a small vial source of 67Cu containing varying amounts of 64Cu were used to
      evaluate the impact of 64Cu on image resolution and activity quantitation,
      respectively. Identical pharmacokinetics for 67Cu and 64Cu was assumed, and the
      radiation dosimetry of 64Cu was assessed using quantitative imaging data for 67Cu
      because the amount of 64Cu could be calculated for any time after 67Cu
      production. MIRD formalism was used to estimate the therapeutic index, defined as
      the ratio of radiation dose to tumor divided by the radiation dose to bone
      marrow. RESULTS: As the amount of 64Cu increased, the full width at tenth maximum
      of the line spread function increased, although there was no significant change
      in full width at half maximum. The number of scatter counts from 64Cu increased
      as the amount of 64Cu or the size of the source region of interest increased.
      When 64Cu was 25% of the total activity, less than 10% of the total 67Cu
      photopeak counts detected with a scintillation camera were attributable to 64Cu.
      Although the tumor radiation dose per unit of activity (cGy/GBq) from 67Cu was
      five times greater than that from 64Cu, the marrow dose (CGy/GBq) from 67Cu was
      only three times greater than that from 64Cu. Therefore, the therapeutic index
      was diminished by the presence of 64Cu. When 64Cu radioimpurity was less than 25%
      of the total activity, there was less than a 10% decrease in the therapeutic
      index. CONCLUSION: The shorter physical half-life of 64Cu relative to that of
      67Cu and slower uptake and longer retention of antibody by tumor than by marrow
      result in a lower therapeutic index for 64Cu. The 25% radioimpurity of 64Cu
      causes less than 10% deviation in activity quantitation and diminution in the
      therapeutic index. The change in therapeutic index is predictable over time and
      can be used to determine the optimal time for radiopharmaceutical administration.

PMID- 8543985
TI  - Dosimetry of an iodine-123-labeled tropane to image dopamine transporters.
AB  - N-(3-Iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane (IPT) is
      an analog of cocaine that selectively binds the presynaptic dopamine transporter.
      The present study sought to measure the radiation dosimetry of IPT in seven
      healthy human volunteers. METHODS: Dynamic renal scans were acquired immediately
      after the intravenous administration of 165 +/- 16 MBq (4.45 +/- 0.42 mCi) of
      [123I]IPT. Between 7 and 12 sets of whole-body scans were acquired over the next
      24 hr. The 24-hr renal excretion fractions were measured from conjugate emission
      scans of 7-11 discreet voided urine specimens. The fraction of the administered
      dose in 11 organs and each urine specimen was quantified from the attenuation
      corrected geometric mean counts in opposing views. Subject-specific residence
      times were calculated for each subject independently by fitting the time-activity
      curves to a multicompartmental model. The radiation doses were estimated with the
      MIRD technique from the residence times for each subject individually before any
      results were averaged. RESULTS: The findings showed that IPT was excreted rapidly
      by the renal system. There were no reservoirs of retained activity outside the
      basal ganglia, where SPECT images in these subjects showed that the mean ratio of
      caudate to calcarine cortex averaged 25:1 at 3 hr after injection (range 19.6-32
      hr). The basal ganglia received a radiation dose of 0.028 mGy/MBq (0.10 rad/mCi).
      The dose-limiting organ in men was the stomach, which received an estimated 0.11
      mGy/MBq (0.37 rad/mCi). In women, the critical organ was the urinary bladder at
      0.14 mGy/MBq (0.51 rad/mCi). CONCLUSION: Relatively high-contrast images of the
      presynaptic dopamine transporters in the basal ganglia can be acquired with 185
      MBq (5 mCi) of [123I]IPT. The radiation exposure that results is significantly
      less than the maximum allowed by current safety guidelines for research
      volunteers.

PMID- 8543986
TI  - PET hydroxyephedrine imaging of neuroblastoma.
AB  - The goals of this investigation were to characterize the uptake of 11C
      hydroxyephedrine (HED) in neuroblastoma and to determine the feasibility and
      potential advantages of utilizing this compound as a tumor imaging agent.
      METHODS: Seven patients with known or subsequently proven neuroblastoma were
      studied. Each patient underwent PET scanning with 11C-HED. Six of seven patients
      underwent scintigraphy with [123I]meta-iodobenzylguanidine (MIBG), and two
      patients were also studied with [18F]FDG PET. For six patients, CT or MR images
      were available for comparison. RESULTS: Neuroblastomas were located by PET
      scanning with 11C-HED in all seven patients. The uptake of HED into
      neuroblastomas was rapid; tumors were evident on images within 5 min
      postintravenous injection. Those lesions in the field of view of the PET camera
      were also identified on [123I]MIBG scintigraphic images. In two patients, tumor
      deposits in the abdomen were better visualized with MIBG scintigraphy due to
      relatively less hepatic accumulation of MIBG than HED. CONCLUSION: PET scanning
      with HED for neuroblastoma results in high quality functional images of the
      tumors that can be obtained within minutes following injection.

PMID- 8543987
TI  - Balancing the budget: will it work?

PMID- 8543988
TI  - Diagnostic performance of a receptor-binding radiopharmacokinetic model.
AB  - The aim of this study was to determine which measurement obtained from a
      radiopharmacokinetic model of a receptor-binding radiotracer provides the highest
      diagnostic performance for the detection of diffuse hepatocellular disease.
      METHODS: Twenty-seven healthy subjects and 46 patients with diffuse
      hepatocellular disease were studied with the receptor-binding
      radiopharmaceutical, 99mTc-galactosyl-neoglycoalbumin. A radiopharmacokinetic
      model was used to produce estimates of receptor concentration [R]o, the scaled
      forward-binding rate constant Kb, hepatic plasma volume, Vh, extrahepatic plasma
      volume, Ve and hepatic plasma flow, F. Receiver operating characteristic analysis
      of each model estimate was conducted. RESULTS: Receptor concentration [R]o and
      the metrics [R]o/tbw and kb[R]o[R]o/tbw provided the best discrimination between
      healthy and diseased liver. The forward-binding rate constant kb and the metrics
      F/Ve and Vh/tbw provided no discrimination. CONCLUSION: Based on simplicity and
      higher measurement precision, [R]o was selected as the most accurate index of
      hepatic function.

PMID- 8543989
TI  - Low probability lung scan in a patient at high risk for pulmonary embolism.

PMID- 8543990
TI  - Cost efficacy of the diagnosis and therapy of renovascular hypertension.
AB  - Numerous competing diagnostic modalities and the lack of data about therapeutic
      benefit result in controversy concerning the identification and treatment of
      renovascular hypertension. METHODS: Meta-analyses were used to examine the cost
      efficacy of renovascular hypertension diagnosis and treatment. Sensitivity,
      specificity and predictive value were calculated for captopril renography,
      Doppler, the captopril test and arteriography. Sensitivities and specificities
      were used to project cost per patient cured or improved for each modality. This
      was compared with the lifetime cost of medical therapy. Cost efficacy was
      calculated using a hypothetical population (1000 patients, a prevalency rate of
      30% for renal artery stenosis, expected cure or improvement rate of 0.77 after
      angioplasty). RESULTS: The sensitivity, specificity and positive predictive
      values were similar for all modalities except the captopril test, which had a
      significantly lower sensitivity. The specificity was similar for all procedures;
      Doppler was highest but was mitigated by a 17% technical failure rate. The cost
      per patient cured or improved is greatest for arteriography and lowest for the
      captopril test. The relationship between cost per patient cured and the number of
      patients diagnosed in the population was calculated (relative value = (1/cost) x
      number patients detected). The relative value of captopril renography and
      arteriography is similar. Doppler and the captopril test have the lowest relative
      value. If angioplasty reduces medication by three drugs, the savings is $5807 to
      $8046 per patient. Surgical therapy is not cost-effective. CONCLUSION: Screening
      for renovascular hypertension is not cost-effective at a prevalence less than
      30%, but captopril renography is equally cost-effective as arteriography and
      obviates the need for an arteriogram in many patients.

PMID- 8543991
TI  - Collaboration using Internet for the development of case-based teaching files:
      report of the Computer and Instrumentation Council Internet Focus Group.
AB  - The Internet and particularly the World-Wide-Web is becoming a useful tool for
      the nuclear medicine community. METHODS: The Computer and Instrumentation Council
      of the Society of Nuclear Medicine convened an Internet Focus group to discuss
      collaboration using the Internet. The prototype application considered was
      development of case-based teaching files using the World-Wide-Web. Teaching file
      cases (clinical history, images, description of findings and discussion) on World
      Wide-Web servers at different institutions are integrated using the Internet. The
      user can navigate from case to case using point-and-click hypertext linking.
      RESULTS: The initial experience with collaboration has been encouraging. An
      etiquette to help foster collaboration has been proposed. Development of quality
      control mechanisms and introduction of peer review were identified as issues
      needing further work. CONCLUSION: The World-Wide-Web offers great potential for
      new forms of collaboration. There is, however, a need to learn how to make best
      use of this new resource.

PMID- 8543993
TI  - Gallium bone scintigraphy.

PMID- 8543992
TI  - Prevalence of adverse reactions in nuclear medicine. Pharmacopeia Committee of
      the Society of Nuclear Medicine.
AB  - This investigation sought to determine the prevalence of adverse reactions to
      radiopharmaceuticals and to nonradioactive drugs used in interventional nuclear
      medicine. We also tabulated all adverse reactions reported to manufacturers of
      radiopharmaceuticals commercially available in the United States. METHODS: A
      prospective 5-yr study was performed of 18 collaborating institutions using a
      questionnaire which enumerated monthly the number of procedures used and adverse
      reactions noted. An algorithm to determine the level of etiologic probability of
      an adverse reaction from an administered radiopharmaceutical was developed. We
      reviewed all available literature on adverse reactions in nuclear medicine.
      RESULTS: During this period, 783,525 radiopharmaceutical and 67,835
      nonradioactive drug administrations were analyzed. Ten of the 18 adverse
      reactions to radiopharmaceuticals were rashes. No patient experiencing an adverse
      reaction to a radiopharmaceutical required hospitalization or had significant
      sequelae. Reproducibility of the adverse reactions algorithm was validated by
      independent evaluation of 30 adverse reaction reports from the U.S. Pharmacopeia
      Society of Nuclear Medicine adverse reaction reporting system. All adverse
      reactions to 49 commercially available radiopharmaceuticals were tabulated and
      referenced. CONCLUSION: Radiopharmaceuticals have an excellent safety record. An
      algorithm to evaluate putative radiopharmaceutical reactions is highly
      reproducible.

PMID- 8543994
TI  - Timing of thallium injection during dobutamine imaging.

PMID- 8543995
TI  - Iodine-123-iodo-lisuride SPECT in Parkinson's disease.
AB  - Recently, [123I]iodo-lisuride was synthesized for possible applications in SPECT
      studies. The purpose of this investigation was to compare the striatal binding
      and kinetics of this radioligand in patients with Parkinson's disease and normal
      controls. METHODS: Six patients with Parkinson's disease and three normal
      controls were examined. After intravenous injection of 111 MBq [123I]iodo
      lisuride, sequential SPECT examinations at 20, 40, 80 and 120 min were performed.
      For each SPECT series the basal ganglia-to-cerebellum ratio of tracer
      accumulation was calculated. In one patient a repeat SPECT examination was
      undertaken under identical conditions to test the reproducibility of the
      procedure. In two other patients a second SPECT examination was performed after
      injection of cold lisuride as a receptor saturation study. In addition, the time
      course of the radioactivity was measured in the plasma and red blood cells in
      each individual. RESULTS: In both patients and controls, the highest tracer
      accumulation was found within the striatum. The basal ganglia-to-cerebellum ratio
      was 1.182 and 1.303 at 20 min, 1.353 and 1.450 at 40 min, 1.490 and 1.533 at 80
      min, 1.550 and 1.583 at 120 min for patients and controls, respectively, which
      was not statistically different. In the saturation study, 50 micrograms and 100
      micrograms cold lisuride led to a 28% and 33% reduction, respectively, of the
      basal ganglia-to-cerebellum ratio at 120 min. The ligand showed a rapid decline
      in plasma and red blood cells. The percent injected dose per liter was calculated
      to be 1.6 and 0.9, respectively, for plasma and red blood cells at 20 min.
      CONCLUSION: Iodine-123-iodo-lisuride SPECT seems useful for imaging intact
      striatal dopamine D2 receptors in patients with Parkinson's disease and may
      provide clinically relevant information for quantitative assessment of the
      availability and integrity of dopamine D2 receptors.

PMID- 8543996
TI  - Radioiodine breast uptake in nonbreastfeeding women: clinical and scintigraphic
      characteristics.
AB  - We studied the scintigraphic and associated clinical characteristics of
      radioiodine breast uptake in nonbreastfeeding thyroid cancer patients undergoing
      routine whole-body radioiodine scanning. METHODS: We performed a retrospective
      review of the radioiodine scans and medical records of 30 prospectively collected
      cases. RESULTS: Twenty-three nonpregnant patients had discontinued breastfeeding
      for a mean of 11.4 mo. Three postmenopausal and four single nulliparous patients
      had radioiodine breast uptake on one or more occasions. This represented about 6%
      of all female patients who had radioiodine scans over a 3-yr period. Four
      patterns of uptake, full, focal, crescentic and irregular, were observed. Breast
      uptake mimicked lung metastasis in nine patients. Expressible galactorrhea and
      moderately elevated prolactin levels were present in 48% and 24%, respectively,
      of patients examined. In 14 patients followed for an average of 11.4 mo, there
      were no consistent changes in the pattern or intensity of breast uptake. In 18
      patients who had both 123I diagnostic and 131I postablation scans within a few
      days, breast uptake was present on both scans in 75%. In four patients, breast
      uptake was present, despite the 4%-9% radioiodine uptake by the thyroid; in one
      patient, iodinated contrast material blocked the uptake of the thyroid gland but
      not of the breast. CONCLUSION: Although the mechanisms of radioiodine breast
      uptake remain unclear, breast uptake should be suspected in all female patients
      with radioiodine uptake in the chest area, even in the absence of a history of
      breastfeeding.

PMID- 8543997
TI  - In vivo demonstration of enzyme activity in endocrine pancreatic tumors:
      decarboxylation of carbon-11-DOPA to carbon-11-dopamine.
AB  - METHODS: We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA
      in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one
      gastrinoma. RESULTS: With L-DOPA labeled with 11C in the beta position, in which
      the radioactive label follows the molecule through decarboxylation to dopamine,
      significant uptake was observed in the tumors. With L-DOPA labeled in the
      carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2
      if decarboxylation takes place, an almost complete lack of uptake is noted.
      CONCLUSION: This study shows that, using selective position labeling, an in vivo
      action of enzymatic activity can be observed with PET and that significant
      decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked
      retention of radioactivity occurs after treatment with somatostatin analogs. It
      is hypothesized that this is a reflection of a reduction of exocytosis which is
      induced by this treatment.

PMID- 8543998
TI  - Bone marrow absorbed dose of rhenium-186-HEDP and the relationship with decreased
      platelet counts.
AB  - Rhenium-186(Sn)-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) has been used
      for palliation of metastatic bone pain. The purpose of this study was to find a
      relationship between the bone marrow absorbed dose and the toxicity, expressed as
      the percentage decrease in the peripheral blood platelet count. METHODS: The bone
      marrow absorbed dose was calculated according to the MIRD model using data
      obtained from ten treatments of patients suffering from metastatic prostate
      cancer; noninvasive and pharmacokinetic methods were used. The bone marrow doses
      were related to toxicity using the pharmacodynamic sigmoid Emax model. RESULTS:
      The mean bone marrow absorbed doses using the noninvasive and pharmacokinetic
      methods were in a close range to each other (1.07 mGy/MBq and 1.02 mGy/MBq,
      respectively). There was a good relationship between the toxicity and the bone
      marrow absorbed dose (r = 0.80). Furthermore, the EDrm50 (i.e., the bone marrow
      absorbed dose producing a 50% platelet decrease) to bone marrow for 186Re-HEDP
      was on the order of 2 Gy. CONCLUSION: Although the function of normal bone marrow
      is affected by metastases in patients with metastatic bone disease, the MIRD
      model can be used to relate toxicity to the bone marrow absorbed dose after a
      therapeutic dosage of 186Re-HEDP.

PMID- 8543999
TI  - Bone SPECT to assess mandibular invasion by intraoral squamous-cell carcinomas.
AB  - It is important for head and neck surgeons planning their operative approach to
      assess tumor infiltration to the mandible by intraoral squamous-cell carcinomas.
      Two- to 3-hr planar bone scintigraphy is sensitive but not specific in detecting
      mandibular invasion by tumor. We evaluated 3-hr SPECT bone scintigraphy, which
      provides better anatomical detail, to determine if it more accurately assesses
      tumor invasion. METHODS: Thirty consecutive patients with proven intraoral
      squamous-cell carcinomas were studied. Semiquantitative assessment of the
      mandible was performed with a three-level graded scoring system, based on
      comparisons of tracer uptake in the mandible to that in the upper cervical
      vertebrae and in an unaffected part of mandible. Lesion-to-cervical spine (L/S)
      count ratios and lesion-to-nonlesion (L/N) count ratios in the mandible on the 3
      hr SPECT images were calculated. RESULTS: All patients with proven tumor invasion
      showed higher tracer uptake than those with normal mandible or other dental
      diseases. The L/S and L/N count ratios on the SPECT images were significantly
      higher in patients with tumor invasion than in those without (L/S, p < 0.001;
      L/N, p < 0.01). L/S ratios provided better differentiation than L/N ratios.
      CONCLUSIONS: Bone SPECT provides a reliable means of assessing tumor invasion to
      the mandible by intraoral squamous-cell carcinomas.

PMID- 8544000
TI  - Comparison of gallium-67-citrate and thallium-201 scintigraphy in peripheral and
      intrathoracic lymphoma.
AB  - We performed this study in an attempt to reconcile the differences with respect
      to 67Ga uptake as a function of tumor grade and type in the literature, as well
      as to determine the sensitivity of 201Tl uptake in both Hodgkin's and non
      Hodgkin's lymphoma. METHODS: Thirty-six (9 with low-grade lymphoma, 11 with
      intermediate-grade lymphoma, 4 with high-grade lymphoma and 12 with Hodgkin's
      lymphoma) patients underwent both 67Ga and 201Tl scintigraphy. Biopsies were done
      on all patients. A semiquantitative rating system was used to make statistical
      comparisons for thallium versus gallium in all lymphoma subgroups, as well as
      comparisons of thallium and gallium to themselves in all subgroups. RESULTS:
      Patient sensitivity was only 56% and site sensitivity was 32% in patients with
      low-grade lymphoma. Conversely, 201Tl sensitivity was 100%, respectively, for
      patients and sites. The difference between 201Tl and 67Ga sensitivity in patients
      with low-grade lymphoma on a site basis was statistically significant. When
      compared to itself in lymphoma subgroups, 201Tl was found to be statistically
      more avid for low-grade lymphoma than for intermediate, high or Hodgkin's
      lymphoma. Gallium-67 sensitivity for low-grade lymphoma was significantly less
      than for Hodgkin's and intermediate grade lymphomas. No significant differences
      were found when 201Tl and 67Ga were compared in the intermediate, high or
      Hodgkin's lymphoma groups. CONCLUSION: Thallium-201 demonstrates significantly
      greater tumor avidity in the low-grade lymphoma group compared to 67Ga citrate.
      Gallium-67-citrate appears relatively nonavid for low-grade lymphoma compared to
      201Tl and is statistically inferior in detecting low-grade lymphoma in comparison
      to its ability to detect intermediate or high-grade lymphomas. Gallium-67-citrate
      should not be considered dependable in evaluating patients with low-grade
      lymphoma. Neither 201Tl or 67Ga is dependable in the evaluation of low-grade
      lymphoma within the abdomen, since gallium avidity for low-grade lymphoma is low
      and gastrointestinal excretion of 201Tl is poorly controlled.

PMID- 8544001
TI  - Quantitation of benzodiazepine receptors in human brain using the partial
      saturation method.
AB  - The in vivo quantification of the benzodiazepine receptor concentration in humans
      using PET and flumazenil (FMZ) is usually based on Scatchard analysis when the
      goal is to avoid blood sampling. The experimental protocols, however, include
      several (at least two) experiments with various specific activities in the same
      subject to obtain a range of bound ligand concentrations. METHODS: We propose the
      partial saturation method, which is based on a natural decrease in bound ligand
      concentration after an FMZ injection with an average dose between a tracer dose
      and a saturation dose. An adequate range of bound ligand concentrations can thus
      be obtained from a single experiment. The free ligand concentration is estimated
      from the PET measurement in the pons after correction for the effect of the small
      receptor site concentration in this reference region. RESULTS: The receptor
      concentration and affinity estimates obtained with this approach in six regions
      of interest agree with previously published values obtained by using more complex
      approaches. Receptor concentration appears to be insensitive to the uncertainties
      with regard to the receptor site concentration in the pons. CONCLUSION: The
      partial saturation protocol can be used to estimate both the benzodiazepine
      receptor concentration and the FMZ affinity in routine examinations in adults (or
      even in children) using a single 40-min experiment without blood sampling.

PMID- 8544002
TI  - Hepatic distribution of blood flow from the superior or inferior mesenteric vein
      mapped by portal scintigraphy with iodine-123-iodoamphetamine.
AB  - We previously reported the clinical meaning of measurements of the relative
      contributions of the superior and inferior mesenteric veins with
      [123I]iodoamphetamine after oral (in an enteric capsule) and rectal
      administration. The same method was used to map blood flow in the liver from both
      of these veins in 82 subjects, 31 with chronic hepatitis and 51 with cirrhosis.
      METHODS: Three hours after administration of a capsule containing 22.8 MBq of
      [123I]iodoamphetamine, data showing hepatic blood flow from the superior
      mesenteric vein were collected for 10 min. Next, 111 MBq of [123I]iodoamphetamine
      was administered rectally and data showing hepatic blood flow from the inferior
      mesenteric vein were collected for 30 min. Shunt indices from the superior and
      inferior mesenteric veins were calculated from these data. RESULTS: In patients
      with chronic hepatitis, blood from the superior mesenteric vein flowed into the
      right lobe or both lobes, but, in some patients with cirrhosis, blood from this
      vein flowed into the left lobe. In some patients with chronic hepatitis, blood
      from the inferior mesenteric vein flowed into the left lobe, but, in most
      patients with cirrhosis, the liver was not visualized during this examination and
      evaluation was not possible. Of the 53 patients in whom blood flow from both
      veins could be evaluated, 47 had blood from the two veins mixed to some extent in
      the liver and 6 had portal streamlining, with blood from the superior mesenteric
      vein going to the right lobe and blood from the inferior mesenteric vein going to
      the left lobe. CONCLUSION: These results suggest that blood flow in the superior
      and inferior mesenteric veins can be found mixed in the liver in most subjects
      with liver disease.

PMID- 8544003
TI  - Detection of prosthetic vascular graft infection using avidin/indium-111-biotin
      scintigraphy.
AB  - Prosthetic vascular graft infection, though rare, carries high morbidity and
      mortality rates; therefore, timely diagnosis is important. Patients, however,
      often present with vague symptoms, and radiological investigations are frequently
      inconclusive. These factors may lead to prolonged periods of observation and
      hospitalization, with the resultant increase in costs and complication rates,
      before reaching a final diagnosis. This prospective study evaluates the use of
      nonspecific avidin/111In-biotin imaging in diagnosing prosthetic vascular graft
      infection. METHODS: Twenty-five patients with a total of 29 grafts were
      investigated. Eighteen patients (19 grafts) had low probability of disease,
      whereas the remaining 7 patients (10 grafts) warranted surgical exploration based
      on clinical, laboratory or radiological evidence. Avidin was first injected
      intravenously and then followed 24 hr later by administration of 111In-biotin.
      Whole-body images were obtained 10 min and 2 hr postinjection of 111In-labeled
      biotin. SPECT imaging was performed 1 hr postinjection. Increased uptake along
      part or the whole length of the graft was considered evidence of graft infection.
      RESULTS: Avidin/111In-biotin scintigraphy correctly identified all infected
      grafts, as confirmed by culturing surgical specimens. In contrast, infection was
      correctly excluded in all but one of the grafts, and long-term follow-up was used
      to assess the presence of infection in patients who did not undergo surgical
      intervention. CONCLUSION: Avidin/111In-biotin scintigraphy is a simple and
      accurate imaging method for the routine diagnosis of vascular graft infection,
      and it may have a role in identifying the disease process in its initial stages,
      thus improving prognosis.

PMID- 8544004
TI  - Nuclear arthrography: combined scintigraphic and radiographic procedure for
      diagnosis of total hip prosthesis loosening.
AB  - Radiographic arthrography and bone scintigraphy are common diagnostic procedures
      used for evaluating total hip prostheses. In this study, both techniques are
      combined, and nuclear contrast imaging (nuclear arthrography) is added. The
      efficacy of the procedures is evaluated. METHODS: After intravenous injection of
      99mTc-methylene diphosphonate (MDP), standard radiographic arthrography was
      performed in 105 patients (107 prostheses). The radiographic contrast medium was
      mixed with insoluble 111In-colloid (5 MBq/20 ml). After completion of the
      radiographic arthrography, nuclear arthrography was performed, and multiple-view
      dualisotope images (111In, 247-keV peak only) were recorded. Images were
      interpreted by superposition of the 111In image and the corresponding 99mTc-MDP
      image, the latter serving as a landmark for the position of the prosthesis and
      osseous structures. Findings at surgery were used as the gold standard. RESULTS:
      In both cemented and uncemented acetabular and femoral components, nuclear
      arthrography performed better than or equal to radiographic arthrography (70%-90%
      and 60%-75%, respectively). Nuclear arthrography had higher diagnostic accuracy
      than 99mTc-MDP images alone. CONCLUSION: Nuclear arthrography is a sensitive
      technique for detection of loosening of prostheses, offering added value over
      radiographic arthrography and bone scanning alone, especially for evaluation of
      the femoral component. Radiographic arthrography remains necessary not only for
      adequate deposition of contrast agents but also for detailed evaluation of
      osseous structures.

PMID- 8544005
TI  - Quantification of renal function with a count-based gamma camera method using
      technetium-99m-MAG3 in children.
AB  - To evaluate renal function quantitatively without blood sampling in children,
      renal uptake by gamma camera renography using 99mTc-MAG3 was compared with plasma
      clearance by a single blood sample method as the reference. METHODS: Twenty
      children (15 boys, 5 girls; aged 2-14 yr) with nephrourological diseases were
      examined prospectively in this study. The patient received an intravenous
      administration of 5 MBq/kg 99mTc-MAG3 which was prepared using a commercially
      available kit. Gamma camera renography was performed and the renal uptake per
      injected dose (%RU) of the 1-min period of postinjection was calculated from a
      background-corrected renogram curve by computer. The plasma clearance (Clmag) of
      99mTc-MAG3 was calculated by the single blood sample method at 35 min
      postinjection. RESULTS: The %RU of the 1-min period in the 1-3 min postinjection
      correlated well with Clmag. The best correlation was observed 1-2 min
      postinjection. The regression equation between total %RU (X) and Clmag (Y)
      (ml/min/1.73 m2) was Y = -98.509 + 20.373X (r = 0.910, s = 84.19) with
      standardization by BSA. The best fit regression equation between individual %RU
      (X) and Clmag (Y) (ml/min/1.73m2) was Y = -43.799 + 19.917X (p = 0.932, s =
      43.27). CONCLUSION: The renal uptake method based on separate counts by gamma
      camera renography using 99mTc-MAG3 does not require a blood sample for
      quantification of renal function and may be potentially more practical in
      children.

PMID- 8544006
TI  - Clinically unsuspected epiglottitis detected by indium-111-white blood cell
      scintigraphy.
AB  - A 62-yr-old woman with a history of mental retardation, paranoid psychosis and
      agitated depression presented with deterioration in her baseline mental status
      and fever. No obvious source of fever was found on clinical exam or on initial
      laboratory studies. An 111In-white blood cell (111In-WBC) study was performed 1
      wk after hospital admission, which revealed increased uptake in the anterior neck
      and oral cavity. Subsequent laryngoscopy revealed a red, swollen epiglottis
      compatible with epiglottitis. While not advocating 111In-WBC scintigraphy as part
      of the workup of epiglottitis, this case is presented to emphasize the possible
      milder presentation of epiglottitis in adults compared to children.

PMID- 8544007
TI  - Comparative radionuclide imaging of metastatic insular carcinoma of the thyroid:
      value of technetium-99m-(V)DMSA.
AB  - We report a case of metastatic insular carcinoma of the thyroid evaluated with
      201TI, 99mTc-MIBI, 99mTc-(V)DMSA, 99mTc-MDP and 131I whole-body scans, which were
      obtained after total thyroidectomy. For the majority of lesions detected in the
      skeleton and soft tissue, 131I images were generally available, although most
      were visualized easier with 99mTc-(V)DMSA. Technetium-99m-MDP images were
      considered better than 99mTc-(V)DMSA images in showing bone lesions but not soft
      tissue lesions. Both 201TI and 99mTc-MIBI scans provided sufficient advantage to
      exhibit neck and mediastinal metastases, but they did not surpass 99mTc-(V)DMSA
      in detecting abdominal or bony lesions. In this patient with various metastases
      from insular carcinoma of the thyroid, 99mTc-(V)DMSA seemed to be the tracer of
      choice for whole-body imaging.

PMID- 8544008
TI  - Technetium-99m-HMPAO SPECT in Sturge-Weber syndrome.
AB  - Technetium-99m-HMPAO interictal SPECT was performed on three pediatric patients
      with Sturge-Weber syndrome (SWS). RESULTS: Brain SPECT of all three patients
      demonstrated markedly diminished tracer localization in the affected hemisphere.
      In one patient, the SPECT abnormality was more extensive than the associated
      abnormalities on CT and MRI. CONCLUSION: Technetium-99m-HMPAO brain SPECT can
      detect cerebral perfusion abnormalities associated with SWS and deserves
      consideration in the imaging evaluation of SWS patients.

PMID- 8544009
TI  - Cerebral perfusion imaging evaluates pharmacologic treatment of unilateral
      moyamoya disease.
AB  - Unilateral Moyamoya disease presents as unilateral stenosis or obstruction of the
      supraclinoid internal carotid artery, which causes cerebral hypoperfusion
      resulting in seizures or TIA-like attacks. In severe cases, surgical treatment is
      performed with superficial temporal artery-middle cerebral artery anastomosis. In
      mild cases, conservative management is the treatment of choice. Flunarizine is a
      calcium ion anti-blocking agent, whose primary effect is that the cerebral
      vessels have been used for the treatment of postcerebrovascular disorders.
      Recently, it has been suggested that flunarizine could be used to treat Moyamoya
      disease. This report documents the efficacy of flunarizine to improve regional
      cerebral perfusion in Moyamoya disease.

PMID- 8544010
TI  - Monitoring gene therapy with cytosine deaminase: in vitro studies using tritiated
      5-fluorocytosine.
AB  - Genetically modified mammalian cells that express the cytosine deaminase (CD)
      gene are able to convert the nontoxic prodrug 5-fluorocytosine (5-FC) to the
      toxic metabolite 5-fluorouracil (5-FU). PET with 18F-5-FC may be used for in vivo
      measurement of CD activity in genetically modified tumors. METHODS: A human
      glioblastoma cell line was stably transfected with the Escherichia coli CD gene.
      After incubation of lysates of CD-expressing cells and control cells with 3H-5-FC
      high-performance liquid chromatography (HPLC) was performed. The uptake of 5-FC
      was measured after various incubation times using therapeutic amounts of 5-FC. In
      addition, saturation and competition experiments with 5-FC and 5-FU were
      performed. Finally, the efflux was measured. RESULTS: We found that 3H-5-FU was
      produced in CD-expressing cells, whereas in the control cells only 3H-5-FC was
      detected. Moreover, significant amounts of 5-FU were found in the medium of
      cultured cells, which may account for the bystander effect observed in previous
      experiments. However, uptake studies revealed a moderate and nonsaturable
      accumulation of radioactivity in the tumor cells, suggesting that 5-FC enters the
      cells only through diffusion. Although a significant difference in 5-FC uptake
      was seen between CD-positive and control cells after 48 hr of incubation, no
      difference was observed after 2 hr of incubation. Furthermore, a rapid efflux
      could be demonstrated. CONCLUSION: 5-Fluorocytosine transport may be a limiting
      factor for this therapeutic procedure. Quantitation with PET has to rely more on
      dynamic studies and modeling, including HPLC analysis of the plasma, than on
      nonmodeling approaches.

PMID- 8544011
TI  - Estimation of neocortical serotonin-2 receptor binding potential by single-dose
      fluorine-18-setoperone kinetic PET data analysis.
AB  - Because it satisfies most of the characteristics required to quantify in vivo
      neocortical serotonin-2 (5HT2) receptors, 18F-setoperone was selected for use in
      PET estimation of the neocortical 5HT2 binding parameters in baboons according to
      a single-dose paradigm. METHODS: The neocortical binding potential (i.e., Bmax/KD
      or the k3/k4 ratio) was assessed by three different methods, with the cerebellum
      taken as the reference structure in all instances. Method 1 was based on a Logan
      Patlak graphical analysis of both cerebellar and neocortical data, which allows
      estimation of the neocortical k3'/k4 ratio; it required a separate estimation of
      k5 and k6 from classical nonlinear least-squares (NLSQ) three-compartment
      modeling of cerebellar data. Method 2 was an original combination of a four
      compartment Logan-Patlak procedure for neocortical data and an NLSQ three
      compartment procedure for cerebellar data, allowing the neocortical k3/k4 ratio
      to be obtained directly. In Method 3, an NLSQ three-compartment procedure was
      applied to cerebellar data and an NLSQ four-compartment procedure to neocortical
      data, allowing separate determinations of k3 and k4 for the neocortex and, in
      turn, the k3/k4 ratio. RESULTS: In all three methods, the arterial plasma input
      function was corrected for the presence of 18F-metabolites, and the vascular
      fraction was either fitted or fixed. Statistical analysis showed no significant
      difference among the k3/k4 values obtained from the three methods. Method 3 was
      the least stable because of an occasional poor NLSQ four-compartment fit on
      neocortical data. Method 2 provided the least cumbersome estimate of the k3/k4
      ratio and was found easy and accurate for generating parametric maps of the 5HT2
      binding potential. CONCLUSION: This method might be useful in clinical
      investigations to provide quantitative assessment of receptor binding potential.
      In semiquantitative investigations, the neocortical-to-cerebellum
      pseudoequilibrium ratio may be adequate, as suggested by the significant
      correlations with measured k3/k4 ratios found here.

PMID- 8544012
TI  - Geometrical technique to determine the influence of monochromatic aberrations on
      retinoscopy.
AB  - A geometrical-optical analysis is developed to predict the reflex observed in
      retinoscopy. The analysis can be expanded to explain the reflex for an eye with
      aberrations. The succession of reflexes across the pupil for each position of the
      retinoscope is represented in a contour plot. The plots demonstrate that
      retinoscopy can be considered a measure of the transverse ray aberration of the
      eye. For an eye with simple defocus this causes the typical with and against
      motions observed with hyperopic and myopic refractive errors. For an eye with
      aberrations we predict more-complex retinoscopic reflexes. This theory is
      confirmed by actual measurements on a human eye with known aberrations.

PMID- 8544013
TI  - Streptococcal necrotizing fasciitis ("flesh-eating strep infection").
AB  - Streptococcal necrotizing fasciitis, popularized in the lay literature as the
      "flesh-eating infection" has gained great notoriety. Necrotizing fasciitis may be
      lethal not only due to its severity, but also because of difficulty in diagnosis
      during its early stages. Absence of immunity against certain streptococcal
      proteins increases the severity of infection. Necrotizing fasciitis may be
      distinguished from other streptococcal skin and soft tissue infections by
      clinical examination, imaging studies, and biopsy. Treatment requires a combined
      medical-surgical approach.

PMID- 8544014
TI  - Jungle medicine revisited: an Oklahoma medical team visits Bolivia.
AB  - Twenty-five adventurous physicians, nurses, oral surgeons, lab technicians, and
      lay support persons visited the remote Bolivian village of Corroico during
      February, 1995. During the next week, they treated 1200 patients with maladies of
      all types. Intestinal parasites, failure to thrive, leishmaniasis, tuberculosis,
      multiple dental caries, and ear, nose and throat infections comprised the
      majority of the conditions treated. Over $50,000 in medications were dispensed
      during the week.

PMID- 8544015
TI  - Child witnesses in Oklahoma.
AB  - Children are often required to testify in court about physical and sexual abuse.
      This article examines the literature related to their testifying and reports the
      experiences of children who were interviewed regarding those experiences. In
      general, the children did not appear to be unduly traumatized by their court
      experiences.

PMID- 8544016
TI  - Quantitation of articular cartilage using magnetic resonance imaging and three
      dimensional reconstruction.
AB  - A quadrature knee coil was used in conjunction with a magnetic resonance imaging
      scanner for quantitation of test phantom volumes, ex vivo bovine cartilage
      thickness, and in vivo human articular cartilage volumes. Optimal magnetic
      resonance parameters were obtained by testing a series of spin-echo and gradient
      echo pulse sequences to determine the sequence that provided the highest
      resolution of articular cartilage and best defined the cartilage interfaces with
      synovial fluid and subchondral bone. Extensive testing revealed that two
      sequences were required to define articular cartilage accurately: a spoiled
      gradient-echo sequence and a steady state free-precession sequence. Three
      dimensional reconstruction and statistical analyses of test phantoms and of
      bovine and human cartilage images were performed. Differences between actual
      phantom volumes and three-dimensional measurements demonstrated that, as magnetic
      resonance slice thickness was increased, the measurement variability also
      increased (coefficient of variation ranging from 1.7 +/- 1.3% for 1.0 mm slice
      thickness to 22.7 +/- 1.9% for 3.0 mm slice thickness). When the phantom volume
      was greater than 1,800 mm3, the intraobserver, interobserver and interscan
      accuracies were greater than 97, 98, and 96%, respectively. This high degree of
      reproducibility pertained for the data on in vivo human cartilage data also. For
      experienced observers, the intraobserver and interobserver reproducibility were
      greater than 98 and 97%, respectively. The interscan reproducibility was greater
      than 98%. These data demonstrate that improved magnetic resonance pulse
      sequencing, in conjunction with three-dimensional reconstruction and measurement
      techniques, can accurately and reproducibly measure the volume of articular
      cartilage. Clinical application of this approach offers the potential for early
      diagnosis of osteoarthritis and for serial, noninvasive assessment of changes in
      articular cartilage volume in response to therapeutic modalities.

PMID- 8544017
TI  - Effects of fluid-induced shear on articular chondrocyte morphology and metabolism
      in vitro.
AB  - This study tested the effects of fluid-induced shear on high density monolayer
      cultures of adult articular chondrocytes. Fluid-induced shear (1.6 Pa) was
      applied by cone viscometer to normal human and bovine articular chondrocytes for
      periods of 24, 48, and 72 hours. At 48 and 72 hours, fluid-induced shear caused
      individual chondrocytes to elongate and align tangential to the direction of cone
      rotation. Fluid-induced shear stimulated glycosaminoglycan synthesis by 2-fold (p
      < 0.05) and increased the length of newly synthesized chains in human and bovine
      chondrocytes. In human chondrocytes, the hydrodynamic size of newly synthesized
      proteoglycans also was increased. After 48 hours of fluid-induced shear, the
      release of prostaglandin E2 from the chondrocytes was increased 10 to 20-fold. In
      human chondrocytes, mRNA signal levels for tissue inhibitor of metalloproteinase
      increased 9-fold in response to shear compared with the controls. In contrast,
      mRNA signal levels for the neutral metalloproteinases, collagenase, stromelysin,
      and 72 kD gelatinase, did not show such major changes. This study demonstrated
      that articular chondrocyte metabolism responds directly to physical stimulation
      in vitro and suggests that mechanical loading may directly influence cartilage
      homeostasis in vivo.

PMID- 8544018
TI  - Effects of basic fibroblast growth factor, transforming growth factor-beta 1,
      insulin-like growth factor-1, and insulin on human osteoarthritic articular
      cartilage explants.
AB  - This study evaluated the effects of basic fibroblast growth factor, transforming
      growth factor-beta 1, insulin-like growth factor-1, and insulin on the
      incorporation of thymidine and sulfate in human osteoarthritic articular
      cartilage. Tissue explants were obtained from 11 patients undergoing total knee
      arthroplasty and were categorized as nonfibrillated or fibrillated cartilage. The
      explants were cultured for 22 days, with changes of medium and growth factor
      every 72 hours, and labeled with [3H]thymidine and [35S]sulfate. Growth factors
      were used in the following concentrations: basic fibroblast growth factor at 1,
      10, and 100 ng/ml; transforming growth factor-beta 1 at 0.5, 5, and 50 ng/ml;
      insulin-like growth factor-1 at 0.15, 1.5, and 15 ng/ml; and insulin at 0.05,
      0.5, and 5 micrograms/ml. Basic fibroblast growth factor decreased thymidine
      incorporation to 70% and sulfate incorporation to less than 20% that of the
      growth factor-free controls. Transforming growth factor-beta 1 had no significant
      effect on thymidine incorporation, whereas the concentrations studied inhibited
      sulfate incorporation to approximately 40% that of the controls. At the
      concentrations tested, insulin-like growth factor-1 had no significant effect on
      incorporation of either thymidine or sulfate. In contrast, insulin significantly
      stimulated the incorporation of both. Compared with growth factor-free controls,
      insulin maximally increased thymidine incorporation by a factor (+/- SEM) of 2.36
      +/- 0.47 and 1.69 +/- 0.19 in nonfibrillated and fibrillated explants,
      respectively; sulfate incorporation was maximally increased 1.60 +/- 0.24 and
      1.92 +/- 0.29-fold for nonfibrillated and fibrillated explants, respectively. Of
      the factors tested, insulin demonstrated the greatest promise for promoting a
      synthetic response that may contribute to the regeneration of osteoarthritic
      cartilage.

PMID- 8544019
TI  - Regulation of chondrocyte maturation by fibroblast growth factor-2 and
      parathyroid hormone.
AB  - Fibroblast growth factor-2 and parathyroid hormone are strong modulators of the
      maturation process of chondrocytes during endochondral ossification. To clarify
      whether and how these agents may exert stage-specific effects during this
      process, we analyzed the responsiveness and phenotypic consequences of treatment
      with fibroblast growth factor-2 or parathyroid hormone on chondrocytes at
      different stages of maturation. Populations of immature lower sternal, maturing
      upper sternal, and hypertrophic tibial growth plate chondrocytes were isolated
      from day 18-20 chick embryos and were allowed to resume the maturation process by
      growth in standard monolayer cultures. Treatment of immature lower sternal
      cultures with as little as 0.1 ng/ml of fibroblast growth factor-2 or 10(-10) M
      parathyroid hormone prevented both the emergence of mature type-X collagen
      synthesizing chondrocytes and the ensuing enlargement of cells that occurred in
      control (untreated) cultures. Similarly, the treatment of cultured early maturing
      upper sternal cells with these factors severely reduced the synthesis of type-X
      collagen and alkaline phosphatase activity and the levels of their respective
      mRNAs. In sharp contrast, when the cultured upper sternal cells were allowed to
      grow and mature further before treatment, the responsiveness to fibroblast growth
      factor-2 was markedly reduced and the responsiveness to parathyroid hormone
      remained strong and largely unchanged. Cultures of hypertrophic tibial growth
      plate cells displayed a similar reduced sensitivity to fibroblast growth factor
      2, as also indicated by the lack of mitogenic effects, and strong sensitivity to
      parathyroid hormone. The phenotypic changes induced by treatment with either of
      these factors were fully reversible when cultures that had been treated were
      placed in control medium. The results demonstrate that fibroblast growth factor-2
      and parathyroid hormone are equally potent in affecting the early stages of
      maturation but exert differential effects as the cells progress along the
      maturation pathway. The factors appear to be part of sequentially acting
      mechanisms to ensure normal progression of chondrocyte maturation during
      endochondral ossification.

PMID- 8544020
TI  - Effects of valgus tibial angulation on cartilage degeneration in the rabbit knee.
AB  - Thirteen adult female rabbits underwent unilateral osteotomy of the proximal
      tibia. In nine animals, 30 degrees of valgus angulation was created; in four
      animals, osteotomy without angulation was performed. After a 12-week survival
      period, the knee joints were processed for histology by staining with hematoxylin
      and eosin and safranin O. Additionally, the chondroitin sulphate epitopes 3-B-3(
      ) and 7-D-4 were evaluated immunohistochemically as markers of osteoarthritis.
      Changes of the articular surface of the tibia were visualized by scanning
      electron microscopy. Light microscopic evaluation by the Mankin et al. scoring
      system revealed mild or moderate damage of the cartilage in the lateral
      compartment of angulated extremities when compared with the control side.
      Immunohistology with the monoclonal 3-B-3 and 7-D-4 antibodies showed no
      increased expression of these epitopes in the lateral compartments of the knee.
      Scanning electron microscopic evaluation of the tibial surfaces revealed slight
      surface damage localized to the central, weight-bearing portion of the lateral
      tibial plateau of angulated extremities. Angulation of 30 degrees led to only
      mild degenerative changes of the cartilage. These results indicate that, in the
      short term, cartilage has considerable capacity to withstand the effects caused
      by severe angulation of the limb.

PMID- 8544021
TI  - Biomechanical properties of third carpal articular cartilage in exercised and
      nonexercised horses.
AB  - The relevance of site and exercise on the biomechanical properties of the
      articular cartilage from the equine third carpal bone were assessed by creep
      indentation testing. Six horses were exercised for 30 minutes three times weekly.
      Another six horses were housed in box stalls and were not exercised. At the
      conclusion of the study, one third carpal bone from each horse was harvested and
      the KLM biphasic material properties of cartilage were determined at 12 sites.
      There was a significant (p < 0.01) effect of site but not exercise on the
      cartilage aggregate modulus, which was significantly lower for sites on the
      dorsal aspect of the radial facet and for all sites on the intermediate facet as
      compared with sites on the palmar aspect of the radial facet of the third carpal
      bone. Exercise significantly increased the permeability constant at all sites
      when compared with the nonexercised group, but there was no difference between
      sites within groups. Exercise also significantly increased Poisson's ratio, but
      only at sites located on the palmar aspect of the radial facet. In general, both
      site and exercise influence the biomechanical behavior of third carpal articular
      cartilage. Inherent differences in cartilage biomechanical properties within a
      joint correlate with the location specificity of cartilaginous lesions in the
      equine midcarpal joint.

PMID- 8544022
TI  - Fatigue behavior of the equine third metacarpus: mechanical property analysis.
AB  - This is the first in a series of experiments to study the fatigue properties of
      equine cannon (third metacarpal) bone specimens from Thoroughbred racehorses.
      Monotonic and fatigue tests to failure were performed in four-point bending on
      diaphyseal specimens in a 37 degrees C saline bath to answer three initial
      questions. (a) Will a linear variable differential transducer yield the same
      elastic modulus as strain gauges? (b) Will fatigue results depend on whether the
      periosteal or endosteal side of the beam is in tension? (c) Are there regional
      variations in the monotonic and fatigue properties of the cannon bone midshaft?
      Eighteen left-right pairs of specimens from six horses were used. One beam of
      each pair was fitted with strain gauges. Fatigue tests were conducted on 24
      specimens under load control at 2 Hz; an initial range of 0-10,000 microstrain
      was used so as to produce failure in a reasonable period of time. There were no
      left-right differences in the fatigue or monotonic properties, and the presence
      of a gauge had no effect on modulus measured by a linear variable differential
      transducer. However, gauge-measured moduli were about 1 GPa less than transducer
      measured values. Fatigue life was independent of which side of the beam was in
      tension, and there were significant variations in mechanical properties around
      the cortex. The lateral region was stiffer than the dorsal region but the latter
      had a longer fatigue life. The fixed cylindrical supports used in this experiment
      eventually produced slight wear grooves, causing artifactual stiffening at the
      end of the load cycle in some specimens. A second experiment using roller
      supports confirmed the reason for this stiffening. It also showed that fatigue
      life was shorter when roller supports were used but regional differences were
      similar.

PMID- 8544023
TI  - Atrophic nonunion can be predicted with dual energy x-ray absorptiometry in a
      canine ostectomy model.
AB  - This study demonstrated that dual energy x-ray absorptiometry can be used to
      distinguish between normal union and atrophic nonunion, with high sensitivity and
      high negative predictive value, by 8 weeks after surgery in a canine model.
      Eighteen adult mixed-breed dogs were divided into two equal groups: normal union
      and atrophic nonunion. In the normal union group, a 5 mm mid-diaphyseal
      transverse ostectomy was performed in the right tibia, and the bone was
      stabilized with a unilateral external fixator. In the atrophic nonunion group, a
      5 mm mid-diaphyseal ostectomy was performed; the distal 1.5 cm of the bone ends,
      including the periosteum, were frozen twice to -20 degrees C using liquid
      nitrogen and thawed slowly twice; and the bone was stabilized with a unilateral
      external fixator. The members of the research team were blinded to the group
      assignments until after all dogs were killed and all data were acquired.
      Radiography and dual energy x-ray absorptiometry of both tibiae were performed at
      weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, and 16 after surgery. All dogs were killed at
      16 weeks, and the torsional stiffness and maximum torque of both tibiae of five
      dogs in each group were determined. Mechanically, the tibiae in the normal union
      group had significantly higher maximum torque (43-fold higher) and torsional
      stiffness (86-fold higher) than the tibiae in the atrophic nonunion group. The
      sensitivity and negative predictive value of dual energy x-ray absorptiometry for
      predicting nonunion were 100% by 8 weeks after surgery. The specificity and
      positive predictive value reached 78 and 82%, respectively, by 16 weeks.
      Radiographic scores were significantly higher for the union group than for the
      nonunion group beginning at 2 weeks after surgery. The earliest time after
      surgery that radiography classified an ostectomy as a nonunion was significantly
      later (4.6 +/- 1.2 weeks) than for dual energy x-ray absorptiometry (2.6 +/- 1.4
      weeks). Before these results can be extrapolated to human applications, further
      animal studies must be performed to evaluate clinically or experimentally induced
      fractures, or both, rather than the well defined ostectomies that were performed
      in this study.

PMID- 8544024
TI  - Bisphosphonate (pamidronate/APD) prevents arthritis-induced loss of fracture
      toughness in the rabbit femoral diaphysis.
AB  - Patients with rheumatoid and other inflammatory arthritis have an increased risk
      for fracture. This study was designed to determine the effect of experimental
      inflammatory arthritis on the material properties (fracture toughness and shear
      modulus) and structural properties (torque, angular deflection, and absorbed
      energy) of femoral diaphyseal bone tested in torsion to fracture, as well as the
      effect on these properties of APD (3-amino-1-hydroxypropylidene-1,1
      bisphosphonate), a drug known to block osteoclast activity. Two dose levels were
      investigated. Experimental inflammatory arthritis was induced by intra-articular
      injection of carrageenan into the right tibiofemoral joint, given over 7 weeks,
      in three groups of animals. Simultaneously, daily subcutaneous injections of APD
      were given to three groups of rabbits. Five groups (12 animals each) were
      established: normal, arthritis, normal/high dose APD, arthritis/high dose APD,
      and arthritis/low dose APD. The diaphyses of each excised right femur were loaded
      to fracture in torsion at an angular deflection rate of 8 degrees/sec. In the
      arthritis group, the fracture toughness was 39% lower than in the normal group,
      and the structural properties all were reduced significantly. By contrast, the
      shear modulus was unaffected by arthritis. In this study, the higher dose level
      (0.3 mg/kg of body weight) of APD prevented loss of fracture toughness and
      maintained the structural properties in experimental inflammatory arthritis; the
      low dose was not effective.

PMID- 8544025
TI  - Induction of bone by a demineralized bone matrix gel: a study in a rat femoral
      defect model.
AB  - Demineralized bone matrix contains osteoinductive factors and stimulates filling
      of gaps and defects with bone; however, it is difficult to handle by itself and
      various preparations have been tested. Demineralized bone matrix with a gel
      consistency now is available for clinical use. We studied, in a femoral segment
      defect in the rat, the effects of rat demineralized bone matrix gel with and
      without a ceramic substratum. This preparation is analogous to the human
      demineralized bone matrix in the same carrier, used clinically for humans. One
      hundred adult male Fischer rats were divided into 10 experimental groups.
      Independent variables included the presence or absence of hydroxyapatite ceramic
      cylinders, the presence of demineralized bone matrix in carrier or carrier alone
      (glycerol), and the duration of observation (1, 2, and 4 months). Defects filled
      with the gel alone had significantly higher radiographic scores for host-graft
      union at 4 months compared with ceramic with the gel, ceramic alone, or carrier
      alone. Demineralized bone matrix gel significantly increased the total histologic
      score for host-graft union, whether ceramic was present or not, and a three-way
      interaction occurred among ceramic, the gel, and time. Demineralized bone matrix
      gel was an effective inducer of bone formation in this model. An additional
      substratum was not required; in fact, significantly more bone was formed in the
      absence of the ceramic cylinder. Neither the gel nor the ceramic were impediments
      to revascularization of the defect. Host-graft union was enhanced by
      demineralized bone matrix gel but not by the ceramic cylinder.

PMID- 8544026
TI  - Tumor osteolysis in osteopetrotic mice.
AB  - Details of the cellular and biochemical mechanisms involved in focal destruction
      of bone at sites of tumor osteolysis are unknown. It has been shown that tumors
      from sarcoma (2472) cell lines induce focal osteolysis in mice by stimulating
      formation and activation of osteoclasts. In this report, the influence of 2472
      tumors on the skeletons of osteoclast-deficient animals (op/op) was studied.
      After op/op femora had been inoculated with 2472 cells, tumors developed and
      focal osteolysis occurred. There were more osteoclasts per histologic section in
      sham-injected femora (19 +/- 5) than in tumor-bearing femora (412 +/- 129) (p <
      0.05). The size of the osteoclasts also increased from 304 +/- 81 microns 2 in
      sham-injected limbs to 407 +/- 62 microns 2 in tumor-bearing limbs (p < 0.001).
      Conditioned media from 2472 op/op tumor explants contained macrophage colony
      stimulating factor. A deficiency of osteoclasts in op/op mice is the result of
      the absence of this factor; therefore, these data introduce the possibility that
      macrophage colony-stimulating factor derived from 2472 tumor may be responsible
      for directing osteoclast-mediated osteolysis at sites of the tumor.

PMID- 8544027
TI  - Dose-dependent response of gamma irradiation on mechanical properties and related
      biochemical composition of goat bone-patellar tendon-bone allografts.
AB  - We studied the effects of gamma irradiation on the dimensions, mechanical and
      material properties, and mature hydroxypyridinium crosslink density of collagen
      in goat patellar tendon-bone specimens. Left and right patellar tendon-bone units
      were removed from 10 adult female goats and were bisected longitudinally. Each
      tendon half was frozen, and then the left halves were exposed to 4, 6, or 8 Mrad
      (40,000, 60,000, or 80,000 Gy) of gamma irradiation. The contralateral tendon
      halves served as controls (no irradiation). Each specimen then was loaded to
      failure in tension, and its soft-tissue midsubstance was processed to measure
      collagen content and hydroxypyridinium crosslink density. Dose-dependent
      reductions in the mechanical properties were found, including 46% (p < 0.01) and
      18% (p < 0.05) reductions in maximum force and stiffness, respectively, at 4
      Mrad. Similar reductions were noted in material properties, including 37% (p <
      0.005) and 8% (p > 0.05) reductions in maximum stress and modulus, respectively,
      at 4 Mrad. These results are consistent with our previous report involving 2 and
      3 Mrad (20,000 and 30,000 Gy) of exposure. We also found significant decreases in
      hydroxypyridinium crosslink density with 6 Mrad of irradiation (p < 0.05).
      However, since only one biomechanical parameter (modulus) correlated
      significantly with only one biochemical measure (hydroxypyridinium crosslink
      density) (p < 0.05), other possible mechanisms also are being explored to more
      fully explain these dose-dependent changes.

PMID- 8544028
TI  - Effect of stress deprivation and cyclic tensile loading on the material and
      morphologic properties of canine flexor digitorum profundus tendon: an in vitro
      study.
AB  - The effect of stress deprivation and cyclic tensile loading on the mechanical and
      histologic properties of the canine flexor digitorum profundus tendon was
      examined using an in vitro system. Stress deprivation resulted in a progressive
      and statistically significant decrease in the tensile modulus over an 8-week
      period. Histologically, stress-deprived tendons demonstrated quantitative changes
      in the morphology and number of cells and in the alignment of collagen. The
      change in tensile properties was not associated with an alteration in the water
      content of the tissue, but the change appeared to be dependent on the presence of
      a viable cell population. Dead (acellular) tendons did not undergo any alteration
      in tensile modulus in this in vitro system. In vitro cyclic tensile loading of
      tendons over a 4-week time period resulted in a significant increase in the
      tensile modulus (93% of the control) compared with that of the stress-deprived
      tendons (68% of the control). This loading regimen also maintained the normal
      histologic pattern of the tendons. The results of this study are similar to those
      previously reported for in vivo studies and suggest that this in vitro model may
      represent a valid system with which to test the effects of various stress
      conditions on the tensile properties of tissues.

PMID- 8544029
TI  - Intraoperative graft tensioning alters viscoelastic but not failure behaviours of
      rabbit medial collateral ligament autografts.
AB  - The effects of three different degrees of intraoperative graft tensioning on
      measures of ex vivo laxity, viscoelastic behaviour, and structural and material
      failure of isolated healing medial collateral ligament autografts were
      investigated in a rabbit model. The grafts were orthotopically replaced at one of
      three different loads (too tight, anatomic, or too loose) and were mechanically
      evaluated after 0, 12, 24, and 48 weeks of healing. Laxity of the ligament was
      influenced by intraoperative graft tensioning at time zero. However, after 12
      weeks of healing, values for laxity were indistinguishable among the experimental
      groups. Cyclic load relaxation, a measure of viscoelastic behaviour, was
      significantly influenced by intraoperative graft tensioning, and this effect
      persisted even after 48 weeks of healing. Grafts placed under excessive tension
      relaxed one-third less than grafts placed under abnormally low in situ tension.
      The relevance of these differences remains to be determined. Intraoperative
      tensioning had no significant influence on characteristics of structural or
      material failure of the graft during the first year of healing. These results
      suggest that, in this model, control of graft tension at the time of placement
      and fixation does not improve the failure characteristics of the medial
      collateral ligament. The structural strength of the grafts collectively improved
      to nearly normal values after 48 weeks; however, material recovery was less
      complete. Failure loads averaged 89% of control values, whereas failure stress
      averaged only 52% after 48 weeks of healing.

PMID- 8544030
TI  - Soft-tissue "flaws" are associated with the material properties of the healing
      rabbit medial collateral ligament.
AB  - This study evaluated microscopic flaws in the healing rabbit medial collateral
      ligament and their significance in terms of the material properties of this
      ligament during healing. A gap injury was created in the midsubstance of the
      medial collateral ligament in the right hindlimb of 15 skeletally mature (12
      months old) New Zealand White rabbits. At postoperative intervals of 3, 6, or 14
      weeks, histomorphometric analysis of the flaws was carried out in subgroups of
      animals. The medial collateral ligaments from four of the left hindlimbs
      (randomly selected) were used as uninjured contralateral controls. In one
      histologic section of each area of scar tissue and the analogous area in the
      controls, specified tissue flaws (blood vessels, fat cells, hypercellular areas,
      loose matrix, disorganized matrix, or a combination of these) were measured by
      four independent and blinded observers. The results showed that the mean total
      area of the flaws, as a percentage of the total section, and the mean area of the
      largest flaw decreased with healing time in each healing group but did not
      achieve control values by 14 weeks. Because it was not possible to test the
      healing medial collateral ligaments mechanically prior to measurement of the
      flaws (due to the destructive nature of failure testing), the data on the flaws
      were compared with the material strength and stiffness of a separate series of
      similarly injured and mechanically tested medial collateral ligaments (data
      published previously). A maximum likelihood statistical analysis showed a very
      strong functional association between the mean area of the largest flaw and the
      stress at failure (p < 0.004) and between the mean flaw area as a percentage of
      the total section area and the elastic modulus (p < 0.001). This study therefore
      demonstrates that it is possible to quantify material flaws in scar tissue in
      rabbit medial collateral ligaments, that these flaws become smaller with healing
      time as the scar remodels, and that flaws are functionally associated with the
      material properties of the ligament in this model (larger flaws with less tensile
      strength and more flaws with less stiffness).

PMID- 8544031
TI  - Combined knee loading states that generate high anterior cruciate ligament
      forces.
AB  - Injuries to the anterior cruciate ligament frequently occur under combined
      mechanisms of knee loading. This in vitro study was designed to measure levels of
      ligament force under dual combinations of individual loading states and to
      determine which combinations generated high force. Resultant force was recorded
      as the knee was extended passively from 90 degrees of flexion to 5 degrees of
      hyperextension under constant tibial loadings. The individual loading states were
      100 N of anterior tibial force, 10 Nm of varus and valgus moment, and 10 Nm of
      internal and external tibial torque. Straight anterior tibial force was the most
      direct loading mechanisms; the mean ligament force was approximately equal to
      applied anterior tibial force near 30 degrees of flexion and to 150% of applied
      tibial force at full extension. The addition of internal tibial torque to a knee
      loaded by anterior tibial force produced dramatic increases of force at full
      extension and hyperextension. This loading combination produced the highest
      ligament forces recorded in the study and is the most dangerous in terms of
      potential injury to the ligament. In direct contrast, the addition of external
      tibial torque to a knee loaded by anterior tibial force decreased the force
      dramatically for flexed positions of the knee; at close to 90 degrees of flexion,
      the anterior cruciate ligament became completely unloaded. The addition of varus
      moment to a knee loaded by anterior tibial force increased the force in extension
      and hyperextension, whereas the addition of valgus moment increased the force at
      flexed positions. These states of combined loading also could present an
      increased risk for injury. Internal tibial torque is an important loading
      mechanism of the anterior cruciate ligament for an extended knee. The overall
      risk of injury to the ligament from varus or valgus moment applied in combination
      with internal tibial torque is similar to the risk from internal tibial torque
      alone. External tibial torque was a relatively unimportant mechanism for
      generating anterior cruciate ligament force.

PMID- 8544032
TI  - Subfracture insult to the human cadaver patellofemoral joint produces occult
      injury.
AB  - The current criterion used by the automotive industry for injury to the lower
      extremity is based on visible bone fracture. Studies suggest, however, that
      chronic joint degeneration may occur after subfracture impact loads on the knee.
      We hypothesized that subfracture loading of the patellofemoral joint could result
      in previously undocumented microtrauma in areas of high contact pressure. In the
      current study, seven patellofemoral joints from human cadavers were subjected to
      impact with successively greater energy until visible fracture was noted.
      Transverse and comminuted fractures of the patella were noted at 6.7 kN of load.
      Approximately 45% of the impact energy then was delivered to the contralateral
      joint. Subfracture loads of 5.2 kN resulted in no gross bone fracture in five of
      seven specimens. Histological examination of the patellae horizontal split
      fracture in the subchondral bone, at the tidemark, or at the interface of
      calcified cartilage and subchondral bone. The trauma appeared predominantly on
      the lateral facet, adjacent to or directly beneath preexisting fibrillation of
      the articular surface. Surface fibrillation was noted in histological sections of
      control patellae (not subjected to impact loading), but occult damages were not
      observed. Although the mechanism of this occult trauma is unknown, similar damage
      has been shown to occur from direct shear loading. As these microcracks can
      potentiate a disease process in the joint, this study may suggest that the
      current criterion for injury, based on bone fracture alone, is not sufficiently
      conservative.

PMID- 8544033
TI  - Torsional loads in the early postoperative period following total hip
      replacement.
AB  - Torques generated in one subject during the early postoperative period were
      measured with a telemeterized total hip component. The patient was examined
      during gait, stair ascent, rising from a chair, and single-limb stance. The
      torques were plotted against both the resultant joint contact force and the force
      component directed along the stem axis. During gait, the maximum torque was 35
      Nm, recorded at a walking velocity of 1.7 m/sec. The peak torques during stair
      ascent and during rising from a seated position were found to be 23 and 15 Nm,
      respectively. The maximum value for torque measured in this study was 37 Nm
      during one attempt at single-limb stance. Comparison of plots for torque versus
      stem-axis component for the four activities shows that the torque increased more
      rapidly for chair exits than for gait up to resultant contact force values of as
      much as 1,000 N. For stair ascent, the same was true to values of 1,400 N. Within
      any given activity, the relationship between stem torque and resultant or stem
      axis force showed considerable variability. These results indicate that
      experiments evaluating the stability of femoral components in total hip
      arthroplasty should incorporate a component directed along the stem axis, as well
      as a component normal to the plane of the prosthesis. The results also suggest
      that theoretical stress analysis models should consider the broad variability in
      the orientation of the joint force at the hip.

PMID- 8544034
TI  - Force attenuation in trochanteric soft tissues during impact from a fall.
AB  - The risk for hip fracture from a fall is known to decrease with increased body
      mass index (weight/height2), a relative measure of obesity. To explore whether
      this reduced risk is due to the protective effect of increased soft-tissue
      cushioning in obese individuals, we used an impact pendulum and surrogate human
      pelvis to conduct simulated fall impact experiments on trochanteric soft tissues
      harvested from the cadavers of nine elderly individuals. For each impact, the
      total applied energy was 140 J. Peak forces ranged from 4,050 to 6,420 N, and
      tissue energy absorption ranged from 8.4 to 81.6 J. Increased tissue thickness
      correlated strongly with both decreased peak force (r2 = 0.91) and increased
      tissue energy absorption (r2 = 0.76). However, peak forces in all cases were
      within 1 SD of previously reported average fracture forces for elderly cadaveric
      femora. This suggests that force attenuation in trochanteric soft tissues alone
      is insufficient to prevent hip fracture in falls in which an elderly person lands
      directly on the hip. In such falls, additional energy-absorbing mechanisms, such
      as breaking the fall with an outstretched hand and eccentric contraction of the
      quadriceps during descent, are likely to be involved if fracture does not occur.

PMID- 8544035
TI  - Imaging of immature articular cartilage using ultrasound backscatter microscopy
      at 50 MHz.
AB  - A high frequency sonographic technique-ultrasound backscatter microscopy-was used
      to visualize the subsurface structure of immature porcine articular cartilage
      from the knee joint. In 20-week-old pigs, all parts that were scanned, except the
      weight-bearing regions of the femoral condyles, demonstrated heterogeneous
      ultrasound backscatter characteristics within the articular cartilage. A
      trilaminar pattern consisting of hypoechoic, hyperechoic, and anechoic layers
      ranging from superficial to deep generally was observed, except in the weight
      bearing regions of the femoral condyles, where a homogeneous anechoic pattern was
      seen. In the younger pigs (6 and 10 weeks old), the trilaminar backscatter
      pattern was not observed. Small, highly echogenic structures that correlated with
      vascular channels in histologic assessment were observed frequently in the
      cartilage of younger pigs, but they were seldom present in the cartilage of 20
      week-old pigs. Structural details, such as disruption of the subchondral bone and
      presence of a thickened fibrous layer on the articular surface at the
      chondrosynovial junction, also were detected with the ultrasound backscatter
      microscope. We concluded that high frequency ultrasound can be used to visualize
      the subsurface structure of immature articular cartilage and some of its
      developmental changes. Further research is required to explain the mechanism
      underlying the observed backscatter characteristics of immature articular
      cartilage and to study its potential for the imaging of pathologic changes.

PMID- 8544036
TI  - Preserving plantar flexion strength after surgical treatment for contracture of
      the triceps surae: a computer stimulation study.

PMID- 8544037
TI  - Diagnostic and prognostic value of K39 recombinant antigen in Indian
      leishmaniasis.
AB  - The recombinant product (rK39) of the 39 amino acid repeats encoded by a kinesin
      like gene of visceral Leishmania spp. was further evaluated by enzyme-linked
      immunosorbent assay (ELISA) for its diagnostic potential in Indian kala-azar (VL)
      and post kala-azar dermal leishmaniasis (PKDL). Anti-rK39 antibodies were highly
      positive in 20 symptomatic cases, including 6 resistant to single or double
      chemotherapy, but became negligible or absent in 9 recently cured patients.
      Endpoint titration of samples from the 20 active cases showed that the anti-rK39
      IgG titers fell within a wide range of 10(-2) to > 10(-6), and that their mean
      was > 1 order of magnitude higher than in VL reported previously. The anti-rK39
      IgG titers were correlated with parasite burden found in the patients and
      remained undiminished in those refractory to chemotherapy. These results indicate
      that: (1) the K39 epitope is conserved in Indian strains of Leishmania donovani,
      (2) the extremely high levels of K39 antibodies in both VL and PKDL suggest the
      application of rK39 for sensitive and specific serodiagnosis, and (3) rK39 ELISA
      is also valuable for prognostic evaluation of both diseases.

PMID- 8544038
TI  - Chloroquine resistance is not associated with drug metabolism in Plasmodium
      falciparum.
AB  - Chloroquine-sensitive and -resistant clones of Plasmodium falciparum were
      incubated in vitro with [3H]chloroquine for 16 hr, and the resulting culture
      supernatants and cell pellets were analyzed by high-performance liquid
      chromatography for evidence of chloroquine metabolism. After separation by normal
      or reverse-phase chromatography, there was no evidence of drug metabolism by the
      chloroquine-resistant P. falciparum. However, a single, unidentified,
      radiolabeled metabolite, which did not coelute with desethylchloroquine, was
      produced by 1 of the chloroquine-sensitive clones. Thus, chloroquine resistance
      does not appear to be due to drug metabolism by the resistant parasites.

PMID- 8544039
TI  - Separation of toxoplasma cysts from brain tissue and liberation of viable
      bradyzoites.
AB  - A method was developed to separate Toxoplasma gondii cysts from mouse brain
      tissue and to liberate intact bradyzoites from cysts. Brains were blended in a
      Waring blender with 20% dextran solution and the homogenate was centrifuged at
      4,000 g for 10 min. Cysts present in the sediment were digested by adding an
      equal amount of a solution containing 1 g NaCl, 1.4 ml HCl, and 1 mg pepsin
      (1:60,000 assay activity) per 100 ml water, and incubated at 37 C for 1 min. This
      method is harmless for bradyzoites, as tested by bioassays in mice. It compares
      favorably with published methods for separating cysts that require 3
      centrifugations to achieve similar results.

PMID- 8544040
TI  - Elevated innate peripheral blood eosinophilia fails to augment irradiated
      cercarial vaccine-induced resistance to Schistosoma mansoni in IL-5 transgenic
      mice.
AB  - Numerous factors contribute to host resistance to infection with Schistosoma
      mansoni. Although several studies have investigated the eosinophil as an effector
      cell of protective responses, its true role remains unclear. In vitro, human, but
      not mouse, eosinophils can kill schistosomula. Studies on schistosome infection
      susceptibility in naive or vaccinated eosinophil-deficient mice have yielded
      conflicting results. Using the gamma-irradiated cercariae (irr-cerc) model, we
      vaccinated interleukin (IL)-5 transgenic mice in parallel with background-matched
      controls (C3H/HeN) to examine whether innate eosinophilia contributes to
      increased protection from a challenge infection. In our laboratory, mean
      peripheral blood eosinophil (PBE) levels in IL-5 transgenic mice were 21,000 mm3,
      whereas in naive C3H/HeN mice this value was 240 mm3. In 3 separate experiments,
      both groups of vaccinated mice showed significant resistance to challenge
      infection. However, there was no significant difference in the percent worm
      reduction between transgenic IL-5 C3H mice (mean % protection = 44.3; range = 42
      45%) and the control C3H/HeN mice (mean % protection = 51.7; range = 41-64%). Our
      findings indicate that high levels of innate PBE due to constitutive production
      of IL-5 do not augment irr-cerc-stimulated immunity.

PMID- 8544041
TI  - In vivo study of artemisinin and its derivatives against primary amebic
      meningoencephalitis caused by Naegleria fowleri.
AB  - Artemisinin and its derivatives, beta-arteether and sodium artesunic acid, have
      been evaluated for activity against experimental primary amebic
      meningoencephalitis and the efficacy of these compounds has been compared with
      that of the standard drug amphotericin B. In vivo experiments in Swiss mice have
      shown that amphotericin B at a dose of 2.5 mg/kg for 5 days produced 100%
      protection in the mice infected intranasally with Naegleria fowleri. Artemisinin,
      beta-arteether, and sodium artesunic acid, even when tested at high doses (60-180
      mg/kg x 5 days), were not curative and showed only slight protection as indicated
      by extension of mean survival time.

PMID- 8544042
TI  - Experimental study of survival strategy of Haemonchus contortus in sheep during
      the dry season in desert areas of the Mauritania.
AB  - The survival of the most common worm of sheep and goats of desert areas,
      Haemonchus contortus, during the dry season is of the utmost importance. It may
      be achieved through long survival of adult worms that may preserve their ability
      to excrete viable eggs or to inhibited development in host and survival as a
      larval stage. Twelve lambs were experimentally infected with larvae obtained at
      the end of the rainy season. The resulting adult worms were able to survive and
      maintain their ability to produce viable eggs that developed into infective
      larvae up to 50 wk after infection. It is concluded that survival of adults
      during the dry season played a major role in transmission from 1 rainy season to
      the next, rather than inhibited development and survival as a larval stage.

PMID- 8544043
TI  - Silver staining for elucidation of the synlophe in trichostrongyle nematodes.
AB  - Staining techniques are relatively rare in the study of parasitic nematodes. A
      novel silver-staining method is described for elucidation of the synlophe (a
      system of longitudinal cuticular ridges), a character of great systematic
      importance among the trichostrongyloid nematodes. Ridges are stained optically
      black and appear in great contrast to the body of the nematode. This method
      augments current use of interference contrast for examination of the synlophe.
      Detailed studies of the configuration of the synlophe in entire specimens are
      possible with standard light microscopy for the first time.

PMID- 8544044
TI  - Karyotype analysis of anuran trypanosomes by pulsed-field gradient gel
      electrophoresis.
AB  - The chromosomes of 12 species and isolates of anuran trypanosomes were
      investigated by pulsed-field gradient gel electrophoresis. Twelve to 16
      chromosomes ranging from 0.45 to 2.2 megabase pairs were found in each of these
      trypanosomes. Minichromosomes were not observed in any of the examined isolates.
      Results indicate that different species of anuran trypanosomes display distinct
      karyotype patterns, and that isolates from the same region are similar. Our
      findings also reveal that most chromosome profiles of these trypanosomes are in
      accordance with isoenzyme and random amplified polymorphic DNA analysis data.

PMID- 8544045
TI  - An increased DNA polymerase activity associated with virulence of Toxoplasma
      gondii.
AB  - DNA polymerase activity of the virulent RH strain of Toxoplasma gondii was
      significantly higher than that of the avirulent ME49 strain, whereas sensitivity
      of the activities of both strains to salt, Mg2+, and inhibitors of mammalian DNA
      polymerases were almost the same. It is suggested that this increased enzyme
      activity of the virulent strain contributes to a faster rate of multiplication of
      the organisms as compared with that of the avirulent strain.

PMID- 8544046
TI  - Sustained growth of Ichthyophthirius multifiliis at low temperature in the
      laboratory.
AB  - Applied and basic research on the ciliate Ichthyophthirius multifiliis, an
      obligate parasite of freshwater fishes, requires passage on fish hosts to
      maintain laboratory stocks. However, continual repeated passage results in
      senescence of parasite clones over time. Because growth and development are
      directly correlated to water temperature, our objective was to grow the parasite
      at low temperature in order to extend the period that the organism remains on the
      fish, thus reducing: (1) the number of passages and (2) the number of fish
      required to maintain the parasite over time. Lowering of water temperature from
      25 C to 9 C resulted in significant slowing of growth on channel catfish
      (parasites remained on fish for 20.4 days at 9 C, as compared to 5-6 days at 25
      C), with no discernible changes in viability, antigenicity, or infectivity. Low
      temperature growth is proposed as an improved method for stable maintenance of I.
      multifiliis cultures in the laboratory.

PMID- 8544047
TI  - Postmortem migration of Hymenolepis diminuta (Cestoidea: Cyclophyllidea) in the
      laboratory rat.
AB  - Postmortem migration is of considerable concern in surveys and studies of
      parasite ecology where accurate estimates of parasite location is crucial. Yet,
      there is no quantitative information documenting this phenomenon. Twenty-seven
      Sprague-Dawley rats were each inoculated with 5 cysticercoids of Hymenolepis
      diminuta. Four weeks postinfection, 15 rats were killed by cervical dislocation.
      The small intestines of 3 rats were removed immediately and fast frozen.
      Additional groups of 3 rats each (experimentals) were processed at intervals of
      30, 60, 120, and 240 min after death (AD). Four additional groups of 3 rats
      (controls) were killed and processed at 30, 60, 120, and 240 min in order to
      assess changes due to circadian movement. Changes in the position of the scolex
      and biomass (dry weight) were assessed as a proportion of small intestine length
      for the following criteria: anterior, median, and posterior location. The only
      significant within-group difference was an anterior shift in median biomass in
      the experimental group. Between-group differences were not evident at 30 min.
      Significant posterior shifts were found in anterior and median scolex position of
      the experimentals at 120 and 240 min AD, respectively. Median and posterior
      biomass shifted significantly anteriorly at 60 and 120 min AD in the experimental
      group, respectively, and worm range was significantly reduced in the
      experimentals at 120 min AD. There appears to be a 30-min period following host
      death in which H. diminuta does not change its position within the rat small
      intestine.

PMID- 8544048
TI  - Efficacy of praziquantel in natural populations of mallards infected with avian
      schistosomes.
AB  - In 1991, mallards (Anas platyrhynchos) on North and South Lake Leelanau in
      Leelanau Co., Michigan were trapped, examined for natural infections of avian
      schistosomes, and treated with praziquantel. Prevalence of infection from the 113
      birds recaptured in 1992 was compared with that of the previous year on these 2
      inland lakes after some of the birds were treated. Infections were determined by
      examining diluted fecal samples for hatched schistosome miracidia. Approximately
      15% of the 366 birds captured the first year homed the second and made up about
      27% of the resident mallard population. Of the birds treated in 1991, only 1.8%
      showed an infection in 1992 compared with 14.6% for previously untreated birds.
      These data indicate that praziquantel is an effective therapeutic agent for
      reducing natural infections of the parasite in mallards. Furthermore, yearly
      treatment of mallards at specific sites may not be necessary for effective
      control of swimmer's itch on North and South Lake Leelanau.

PMID- 8544049
TI  - A method for immunoisolation of sporocysts of Schistosoma mansoni in
      nonsusceptible snails.
AB  - A technique is described for immunoisolation of sporocysts of Schistosoma mansoni
      in nonsusceptible Biomphalaria glabrata by microencapsulation in agarose. Based
      on histological evidence, all 11 microencapsulated sporocysts implanted into 3
      schistosome-resistant 13-16-R1 snails were alive at 72 hr postimplantation,
      although in a developmentally retarded condition. However, among 146 sporocysts
      derived from miracidia that had penetrated 5 snails, 96% were dead by 72 hr.
      These results suggest that hemocyte contact is necessary for rapid sporocyst
      death in vivo.

PMID- 8544050
TI  - Genetic resistance against acute toxoplasmosis depends on the strain of
      Toxoplasma gondii.
AB  - The role of the strain of Toxoplasma gondii in genetic control of resistance
      against acute infection with T. gondii was studied with 2 strains of T. gondii,
      which differ in their virulence and genotype. Following peroral infection with 10
      cysts of the C56 strain, C57BL/6 (H-2b) and C3H/HeN (H-2k) mice died
      significantly earlier than BALB/c mice (H-2d) mice, although all of the mice
      eventually died of acute toxoplasmosis from 10 to 23 days after infection. There
      was no significant difference in time to death between C57BL/6 mice and C3H/HeN
      mice. In peroral infection with 100 cysts of the less virulent ME49 strain, all
      C57BL/6 mice died of acute toxoplasmosis from 7 to 10 days after infection.
      C57BL/6 mice died significantly earlier following infection with the ME49 strain
      than with the C56 strain, whereas all C3H/HeN mice infected with the ME49 strain
      survived as did BALB/c mice. These results indicate that genetic control of
      resistance against acute infection with T. gondii differs depending on the strain
      of T. gondii.

PMID- 8544051
TI  - Presidential address. Peeling the cosmic onion.

PMID- 8544052
TI  - Introduction of Richard W. Komuniecki as the Henry Baldwin Ward Medalist for
      1995.

PMID- 8544053
TI  - Acceptance of the 1995 Henry Baldwin Ward Medal.

PMID- 8544054
TI  - Presentation of the President's Special Award for Distinguished Service.

PMID- 8544055
TI  - Host grooming and the transmission strategy of Heligmosomoides polygyrus.
AB  - Grooming behavior may play a part in the transmission of the gastrointestinal
      nematode, Heligomosomoides polygyrus in the mouse host. After infective larvae
      are placed on individually housed mice, significantly higher numbers of adult
      worms were recovered from the small intestine of mice that were allowed to self
      groom when compared to infection levels in mice that had been fitted with
      Elizabethan collars to prevent self-grooming. Larvae placed on a single mouse
      housed with 3 other untreated mice resulted in all mice in the group becoming
      infected, suggesting that allogrooming may also be important in parasite
      transmission. A significantly higher percentage of larvae nictate on rough
      surfaces such as damp peat moss substrate when compared to smooth surfaces such
      as 0.5% agarose. Mice exposed to larvae placed on peat moss substrate have
      significantly higher infection levels when compared to mice exposed to larvae on
      a 0.5% agarose substratum, suggesting that natural transmission of infective L3
      larvae in mice may be dependent on a substratum type that allows nictation
      behavior. A significantly higher percentage of worms were attracted to mouse
      urine and mouse and rat epidermal lipids when compared to deionized water
      controls in an in vitro preference assay, suggesting an attraction to host
      specific signals. These results support the hypothesis that transmission of this
      parasite is an active process involving movement of the infective larvae of H.
      polygyrus into the host's active space where they are ingested during grooming
      behavior.

PMID- 8544056
TI  - Larval density and feeding success of Ixodes scapularis on two species of
      Peromyscus.
AB  - One potential mechanism for the regulation of tick populations is density
      dependent feeding success on vertebrate hosts. In a series of laboratory
      experiments, we tested whether the density of larval Ixodes scapularis on the
      mice Peromyscus maniculatus and Peromyscus leucopus influenced tick feeding
      success. For both host species, the proportion of ticks feeding to repletion was
      constant (approximately 40-50%) over a range of infestation from 5 to 100 ticks
      per mouse. For P. leucopus, neither mass nor molting success of fed ticks was
      significantly related to tick density on the host. However, for P. maniculatus,
      we observed a statistically significant increase in molting success with
      increasing tick density on hosts, thus demonstrating facilitation rather than
      density-dependent regulation. Although results were not statistically
      significant, we observed a tendency for previously exposed P. leucopus to support
      lower tick feeding success than naive mice; however, even for previously exposed
      mice, tick feeding success was not density dependent. Our results do not support
      the notion that density-dependent feeding on hosts regulates density of I.
      scapularis populations at the numbers tested.

PMID- 8544057
TI  - Genetics of resistance to Trypanosoma congolense in inbred mice: efficiency of
      apparent clearance of parasites correlates with long-term survival.
AB  - To study the genetic parameters of resistance to Trypanosoma congolense
      infection, highly susceptible BALB/c and relatively resistant C57BL/6 mice were
      crossed to produce reciprocal F1 and F2 offspring. Mice were infected with T.
      congolense and monitored for parasitemia within the first 2 wk and also for their
      survival periods. BALB/c mice showed unrestrained parasite growth to the time of
      death (median survival period, msp = 12.0 days), whereas in C57BL/6 mice,
      parasitemia reached an initial peak on day 6 and was followed by a rapid apparent
      clearance of the parasites in an average period of 3 days. Their msp was 163.0
      days. The F1 mice cleared the parasites, following the first peak of parasitemia,
      in an average period of 4 days and had an msp of 69.5 days. Thus, the F1
      offspring displayed an intermediate phenotype between susceptible and resistant
      parents in terms of parasite clearance and survival period. Resistance in F2
      mice, as measured by survival times, was inherited as a polygenic trait. Among F2
      mice, there was an inverse correlation between the time taken to clear the
      initial wave of parasitemia and the survival period, r = -0.58; P < 0.05. Thus,
      the pattern of control of the parasites following the first peak of parasitemia
      appears to be a good predictive factor for the survival period of mice infected
      with T. congolense.

PMID- 8544058
TI  - Mediation of immunity to Toxoplasma gondii oocyst shedding in cats.
AB  - Immunity to Toxoplasma gondii, as measured by oocyst shedding, was studied in
      cats. In 3 trials, 12 3-mo-old T. gondii-free cats were fed tissue cysts of the
      ME-49 strain of T. gondii. All cats shed T. gondii oocysts for approximately 1 wk
      starting 3-5 days after ingesting tissue cysts. One cat became ill because of
      toxoplasmic pneumonia and was killed 17 days after inoculation. The remaining
      cats remained clinically normal. Approximately 3 mo after primary infection,
      these 11 cats (immune) and 11 age-matched or littermate uninfected cats
      (nonimmune) were challenged orally with tissue cysts of the ME-49 strain. In
      trials 1 and 3, 1 immune and 1 nonimmune cat were killed at 36 hr, 60 hr, 5 days,
      and 12 days after challenge and the development of T. gondii in intestines was
      studied histologically; in trial 2, cats were killed at 36 hr, 60 hr, and 5 days
      only. None of the "immune" cats shed oocysts after challenge. Asexual T. gondii
      types were found at 36 and 60 hr and at 5 days, indicating partial development of
      T. gondii in the intestine of immune cats. There were no significant differences
      in lymphocyte CD4+/CD8+ from spleen, popliteal, and mesenteric lymph nodes of
      immune cats compared to nonimmune cats.

PMID- 8544059
TI  - Long-term antibody responses of cats fed toxoplasma gondii tissue cysts.
AB  - As part of a long-term study on immunity to oocyst shedding, 12 4-6-mo-old cats
      were inoculated orally with tissue cysts of the ME-49 strain (6 cats) or the TS-2
      strain (6 cats) of Toxoplasma gondii. Two cats fed the ME-49 strain died or were
      killed because of acute toxoplasmosis 12 and 13 days after inoculation (DAI),
      respectively. On day 39 after primary infection, 5 cats (2 infected with the ME
      49 strain and 3 infected with the TS-2 strain) were challenged orally with tissue
      cysts of the ME-49 strain. One cat died following rechallenge infection due to
      causes unrelated to toxoplasmosis. Seventy-seven months after primary infection,
      the remaining 9 cats were challenged orally with tissue cysts of the P89 strain
      of T. gondii. Blood samples were obtained weekly or monthly and sera were
      analyzed for antibodies to T. gondii using the modified agglutination test (MAT),
      the Sabin-Feldman dye test (DT), and the enzyme-linked immunosorbent assay
      (ELISA) for IgM (IgM-ELISA) or IgG (IgG-ELISA). The MAT was performed using both
      formalin-fixed (FF) and acetone-fixed (AF) tachyzoites. The MAT (FF) was the most
      sensitive test; cats seroconverted within 14 DAI and high titers (> 10,000)
      persisted > 6 yr, although cats had no clinical signs. The MAT titers using the
      AF detected recent exposure and titers declined sharply after 2 mo
      postinoculation. DT and ELISA titers were lower and developed slower than MAT
      titers. Fluctuations in antibody titers were limited to 8-fold during the 6-yr
      observation period. Anamnestic serum antibody responses were seen in 2 cats after
      the final challenge, but not after first challenge.

PMID- 8544060
TI  - Preimmune resistance to Toxoplasma gondii in aged and young adult mice.
AB  - Aged individuals are more susceptible to certain infections than are young
      adults. To investigate the relative resistance capabilities of aged and young
      adult mice, responses that are induced within the first week of a Toxoplasma
      gondii infection, which are known to be involved in preimmune resistance, were
      compared in young adult and aged mice. Aged mice did not differ reproducibly from
      young adults in numbers of induced Thy-1+ CD4- CD8- cells or interferon-gamma
      levels. Numbers of induced CD4+ and CD8+ T cells, associated with acquired
      immunity, were as high in aged mice as in young adults. Natural killer cell
      activity, although induced to a high level, was lower in aged mice. Aged mice
      thus are capable of inducing a mechanism of preimmune resistance to T. gondii and
      presumably other infectious agents. Nonetheless, aged mice died within 8-12 days
      after intraperitoneal or peroral inoculation of 500 T. gondii cysts, whereas
      young adult mice survived. Causes other than an age-related impairment in
      preimmune resistance mechanisms are apparently responsible for the increased
      susceptibility of aged mice to T. gondii infection.

PMID- 8544061
TI  - Phenotypes of Heligmosomoides polygyrus selected to survive protective immunity
      in quackenbush mice.
AB  - The survival of Heligmosomoides polygyrus phenotypes passaged selectively through
      naive (Hpn) and immune (Hpa) outbred Quackenbush (Q) mice was compared in Q mice
      immunized passively with normal (NMS) and immune mouse serum (IMS). IMS raised
      against Hpn(Q) worms (IMS-N) was 93% and 92% protective against Hpn(Q) and Hpa(Q)
      phenotypes, respectively; IMS against Hpa(Q) (IMS-A) conferred 93% protection
      against the Hpn(Q) phenotype but gave only 45% protection against the adapted
      Hpa(Q) parasites (P < 0.01). IMS-A had less anti-parasite IgG reactivity than did
      IMS-N (P < 0.05). A 34-kDa antigen from male Hpn(Q), but not Hpa(Q) worms, and an
      antigen at 56 kDa in male Hpa(Q), but not Hpn(Q) parasites, reacted on
      immunoblots with both sets of IMS. Thus, it appeared that Hpa(Q) worms endured
      higher levels of protective immunity than did Hpn(Q) worms and that Hpa(Q) and
      Hpn(Q) phenotypes had different antigens, which, however, did not lead to
      phenotype-specific immunity. This reflects the complexity of host-parasite
      interactions.

PMID- 8544062
TI  - Schistosoma mansoni: changes in the albumen gland of Biomphalaria glabrata snails
      selected for nonsusceptibility to the parasite.
AB  - The LAC-line strain of the snail Biomphalaria glabrata has very low
      susceptibility to the parasite Schistosoma mansoni and a very low reproductive
      potential. Upon examination of the reproductive tract of these snails, light and
      electron microscopy revealed obvious abnormalities in the albumen gland.
      Secretory cells that are normally cuboidal in susceptible NMRI (F0) snails were
      squamous in LAC-line snails. These LAC-line cells contained small secretory
      granules and negligible rough endoplasmic reticulum and Golgi, compared to large
      granules and an extensive array of both organelles in F0 albumen gland cells.
      Comparative analyses of soluble protein extracts of F0 and LAC-line albumen
      glands showed several qualitative differences. Among the most prominent was an 18
      kDa protein in F0 snails that was remarkably reduced in the soluble protein
      extracts of LAC-line snails. Also, metabolic incorporation of [35S]-methionine
      was impaired in LAC-line albumen glands. Whether these albumen gland changes are
      caused by decreased susceptibility to parasitism is yet to determined.

PMID- 8544063
TI  - Noninfectious sporozoites in the salivary glands of a minimally susceptible
      anopheline mosquito.
AB  - In studies to evaluate vector-malaria parasite relationships, we have found that
      Anopheles albimanus is minimally susceptible to the rodent malaria parasite
      Plasmodium yoelii. Normally, less than 10% of A. albimanus develop oocyst
      infections compared to 80-100% for Anopheles stephensi and Anopheles freeborni
      mosquitoes. Although sporozoites produced in A. albimanus invade the salivary
      glands, they are not infectious to BALB/c or ICR mice. In 11 experiments with
      sporozoites from A. albimanus, intravenous inoculations of up to 24,000
      sporozoites in individual mice failed to produce host infections. In contrast,
      inoculation of 300 sporozoites obtained from the salivary glands of A. stephensi
      and A. freeborni always infected mice. The noninfectious sporozoites from A.
      albimanus were morphologically similar to the infectious sporozoites from A.
      stephensi and yielded 4+ circumsporozoite precipitin reactions when incubated
      with a monoclonal antibody against the circumsporozoite protein of P. yoelii. The
      presence of noninfectious sporozoites in the salivary glands of A. albimanus
      suggests that this minimally susceptible vector either possesses a toxic factor
      that abolishes sporozoite infectiousness or lacks a critical substance needed by
      the sporozoite to become infectious. Sporozoite infectiousness was neither
      attenuated by incubation of infectious sporozoites with A. albimanus salivary
      glands nor restored when noninfectious sporozoites were incubated with A.
      stephensi salivary glands. These studies provide a starting point for defining
      the biological basis of sporozoite infectivity.

PMID- 8544064
TI  - Identification of opossums (Didelphis virginiana) as the putative definitive host
      of Sarcocystis neurona.
AB  - Sarcocystis neurona is an apicomplexan that causes equine protozoal
      myeloencephalitis (EPM) in North and South America. Horses appear to be an
      aberrant host, because the merozoites continually divide in the central nervous
      system, without encysting. The natural host species has not previously been
      identified. The small subunit ribosomal RNA (SSURNA) gene of S. neurona was
      compared to those of Sarcocystis muris, Sarcocystis cruzi, Toxoplasma gondii, and
      Cryptosporidium parvum to identify a unique region suitable for a species
      specific amplification primer. The S. neurona SSURNA primer was used in a
      polymerase chain reaction (PCR) assay for the purpose of identifying this
      organism in feces and intestinal digest of wildlife specimens. Sporocysts were
      isolated from 4 raccoons (Procyon lotor), 2 opossums (Didelphis virginiana), 7
      skunks (Mephitis mephitis), 6 cats (Felis catus), 1 hawk (Accipiter sp.), and 1
      coyote (Canis latrans). The S. neurona SSURNA PCR assay and a control PCR assay
      using protist-specific primers were applied to all sporocyst DNA samples. All
      sporocyst DNA samples tested positive on the control assay. The SSURNA PCR assay
      yielded a 484-bp product only when applied to opossum samples. The SSURNA gene of
      both opossum sporocyst samples was sequenced to determine its relationship to the
      S. neurona SSURNA gene. The sequence had 99.89% similarity with S. neurona. This
      suggests that opossums are the definitive host of S. neurona.

PMID- 8544065
TI  - Isolation and characterization of Trichinella pseudospiralis Garkavi, 1972 from a
      black vulture (Coragyps atratus).
AB  - A nematode from the genus Trichinella was observed in histological sections of
      breast and tracheal muscles from a black vulture Coragyps atratus from Alabama.
      Larvae obtained from breast muscle tissue that had been refrigerated for 8 days
      were infectious for laboratory mice. No nurse cell was observed around larvae in
      the black vulture or in experimentally infected mice examined 7 or 9 wk
      postinoculation. The identity of the parasite as Trichinella pseudospiralis was
      confirmed by DNA hybridization using the species-specific probe, pTsp 5.32.
      Infectivity trials showed that this isolate was also infective for pigs and
      chickens. This is the first report of isolation and transmission of T.
      pseudospiralis from an animal from North America.

PMID- 8544066
TI  - Four new gymnophallid digeneans from rice rats, willets, and molluscs in Florida.
AB  - Gymnophalloides heardi n. sp. differs from Gymnophalloides tokiensis Fujita, 1925
      and Gymnophalloides seoi Lee et al., 1993 in the smaller body size, presence of a
      single, lobed vitellarium, and elongate seminal vesicle. In contrast with other
      gymnophallid digeneans that utilize avian and bivalve hosts, G. heardi is the
      first species to be reported from a rodent Oryzomys palustris (Harlan); its
      second intermediate host is a pulmonate gastropod, Melampus bidentatus (L.).
      Three gymnophallid species were found in the willet Catotrophorus semipalmatus.
      Parvatrema bushi n. sp. differs from Parvatrema borinquenae Cable, 1953 in the
      sucker ratios, arrangement of the bean-shaped vitellarium overlapping the ventral
      sucker, and the shallow genital atrium. Paragymnophallus kinsellai n. sp. differs
      from Paragymnophallus odhneri Ching, 1973 in the smaller body size, smaller
      sucker ratio, sharp spines, and highly lobed vitellarium. The third species found
      in willets was P. borinquenae; its metacercaria was found in a new gastropod host
      Cerithidea scalariformis (Say). The metacercariae, cercariae, and sporocysts of
      Parvatrema polymesoda n. sp. were found in the digestive gland of the bivalve
      Polymesoda maritima. The new species differs from both P. bushi and P.
      borinquenae in the small, bilobed vitellarium, presence of numerous sensory
      papillae around the oral sucker, a crenulated ventral sucker, and relatively
      prominent lateral papillae.

PMID- 8544067
TI  - Sarcocystis falcatula from passerine and psittacine birds: synonymy with
      Sarcocystis neurona, agent of equine protozoal myeloencephalitis.
AB  - Equine protozoal myeloencephalitis (EPM) is a neurologic disease of horses caused
      by Sarcocystis neurona. The horse is a dead-end host for S. neurona and the
      definitive and intermediate hosts have not previously been identified. We
      hypothesized that S. neurona is actually Sarcocystis falcatula, a parasite that
      cycles in nature between Virginia opossums (Didelphis virginiana) and any of a
      variety of avian intermediate hosts. We extracted DNA from S. falcatula
      sarcocysts in the muscle of a brown-headed cowbird (Molothrus ater) and from
      schizonts in a fixed specimen of lung from a Moluccan cockatoo (Cacatua
      moluccensis). Three segments of the small subunit ribosomal RNA (SSURNA) gene,
      containing a total of 742 nucleotides, were amplified by the polymerase chain
      reaction, sequenced, and compared with the SSURNA sequence from two isolates of
      S. neurona. The S. falcatula sequence was identical to the sequence of the S.
      neurona isolate UCD-1 and differed in only 3 positions from isolate SN5. Recent
      evidence, also based on SSURNA sequences, implicates the opossum as the
      definitive host of S. neurona. Based on the SSURNA gene sequences S. falcatula
      and S. neurona are synonymous, thus the parasite cycles between opossums and
      birds maintaining a reservoir of the organism from which horses can be infected.

PMID- 8544068
TI  - Nematodes of armadillos in Paraguay: a description of a new species Aspidodera
      esperanzae (Nematoda: Aspidoderidae).
AB  - Twelve species of nematodes comprising 9 genera were recovered from the
      gastrointestinal tract of 2 Euphractus sexcinctus and 2 Dasypus novemcinctus
      captured in the Department of San Pedro, Paraguay. All armadillos were infected
      with 1 or more species of nematode. The following nematodes were recovered:
      Mazzia mazzia, Spirura guianensis, Trichohelix tuberculata, Ancylostoma sp.,
      Moennigia complexus, Moennigia pintoi, Ascaris dasypodina, Cruzia tentaculata,
      Aspidodera fasciata, Aspidodera scoleciformis, Aspidodera esperanzae n. sp., and
      Heterakinae gen. sp. This report describes a new species of the Aspidodera
      nematode, Aspidodera esperanzae n. sp., the first species to be reported bearing
      cephalic cordons made up of 7 longitudinal loops in the subfamily of
      Aspidoderinae. This study also documents a new host record for S. guianensis and
      shows a new geographical distribution in Paraguay for M. mazzia, S. guianensis,
      T. tuberculata, M. complexus, and M. pintoi.

PMID- 8544069
TI  - Five new species of Acanthobothrium van Beneden, 1849 (Eucestoda: Tetraphyllidea:
      Onchobothriidae) in stingrays from 1he Gulf of Nicoya, Costa Rica.
AB  - Five new species of Acanthobothrium are described in stingrays from the Gulf of
      Nicoya, Costa Rica. Acanthobothrium costarricense n. sp. in Dasyatis longus, most
      similar to Acanthobothrium lilium, Acanthobothrium lineatum, and Acanthobothrium
      himanturi, has bothridial hooks averaging 125 microns (lateral) and 145 microns
      (medial) long, an average of 47 testes per proglottis, cirrus sacs averaging 187
      microns long, and asymmetrical ovarian lobes with poral lobes reaching the
      posterior margin of the cirrus sac, and aporal lobes reaching the middle of the
      cirrus sac. Acanthobothrium cimari n. sp. in D. longus, most similar to A.
      lilium, A. lineatum, A. himanturi, A. costarricense, and Acanthobothrium
      semnovesiculum, has bothridial hooks averaging 117 microns (lateral) and 121
      microns (medial) long, an average of 50 testes per proglottis, cirrus sacs
      averaging 164 microns long, and asymmetrical ovarian lobes with poral lobes
      reaching the posterior margin of the cirrus sac, and aporal lobes reaching the
      level of the vagina. Acanthobothrium puntarenasense n. sp. in D. longus,
      distinctive in having a very small scolex relative to the width of the cephalic
      peduncle similar to Acanthobothrium microcephalum, has bothridial hooks averaging
      111 microns (lateral) and 117 microns (medial) long, an average of 50 testes per
      proglottis, cirrus sacs averaging 170 microns long, and asymmetrical ovarian
      lobes with poral lobes reaching the posterior margin of the cirrus sac, and
      aporal lobes reaching the middle of the cirrus sac. Acanthobothrium vargosi in D.
      longus, most similar to Acanthobothrium brevissime, Acanthobothrium tasajerasi,
      Acanthobothrium urotrygoni, and Acanthobothrium campbelli, has bothridial hooks
      averaging 130 microns (lateral) and 133 microns (medial) long, an average of 25
      testes per proglottis arranged in 2 single rows, cirrus sacs averaging 91 microns
      long, and asymmetrical ovarian lobes with poral lobes reaching the posterior
      margin of the cirrus sac, and aporal lobes reaching the middle of the cirrus sac.
      Acanthobothrium campbelli n. sp. in Urotrygon chilensis, most similar to a A.
      brevissime, A. Vargasi, A. lineatum, A. himanturi, and A. urotrygoni, has
      bothridial hooks averaging 108 microns (lateral) and 111 microns (medial) long,
      an average of 19 tester per proglottis arranged in 2 nearly linear rows, cirrus
      sacs averaging 74 microns long, and asymmetrical ovarian lobes with the poral
      lobe reaching the posterior margin of the cirrus sac, and the aporal lobes
      reaching the middle of the cirrus sac.

PMID- 8544070
TI  - Ascarophis mexicana n. sp. (Nematoda: Cystidicolidae) from two species of
      Epinephelus (Pisces) from the Gulf of Mexico in southeastern Mexico.
AB  - A new cystidicolid nematode, Ascarophis mexicana n. sp., is described from the
      stomach of 2 species of the genus Epinephelus, E. morio and E. adscensionis
      (Pisces: Serranidae), from the Gulf of Mexico, southeastern Mexico (states of
      Yucatan and Veracruz). It is distinguished mainly by small body measurements
      (body length of male and female 3.39-4.18 mm and 5.94-6.23 mm, respectively), a
      conspicuously long left spicule (1.58-2.05 mm), length ratio of spicules (1:10
      12), and by eggs provided with 2 filaments on 1 pole. Ascarophis mexicana is the
      second Ascarophis species known to parasitize fishes of the genus Epinephelus
      (groupers).

PMID- 8544071
TI  - Syncoelicotyloides zaniophori n. sp. (Monogenea: Microcotylidae) from the gills
      of Coryphaenoides zaniophorus (Macrouridae) from the Gulf of Mexico.
AB  - Syncoelicotyloides zaniophori n. sp. (Monogenea: Microcotylidae) is described
      from the gills of the macrourid fish Coryphaenoides zaniophorus caught in the
      DeSoto Canyon area in the northeastern part of the Gulf of Mexico. This new
      species is differentiated from Syncoelicotyloides macruri Mamaev and Brashovjan,
      1989 by its body size, number of testes, length of copulatory organ spines,
      morphology of immature portion of germarium, size and morphology of egg, and
      host.

PMID- 8544072
TI  - The demise of a phylum of protists: phylogeny of Myxozoa and other parasitic
      cnidaria.
AB  - The notion that members of the phylum Myxozoa Grasse, 1970 do not properly belong
      in classifications of protists has frequently been suggested because the
      infective spores of these parasites are not unicellular. Systematists have failed
      to be decisive about myxozoan phylogenetic affinities, either finding the
      suggestion of a cnidarian connection to be preposterous or considering the recent
      suggestion of a relationship with nematodes to be an obvious failure of molecular
      phylogenetics. Thus, the group has remained in classifications as a protistan
      phylum in its own right. The ultrastructure of the development of myxozoans was
      critically re-examined in order to more fully explore the possibility of
      morphological synapomorphies with metazoan taxa. These morphological characters,
      in combination with small ribosomal subunit gene sequences, were used in a
      phylogenetic analysis in order to assess myxozoan origins. The results
      unequivocally support the inclusion of myxozoans as a clade of highly derived
      parasitic cnidarians, and as sister taxon to the narcomedusan Polypodium
      hydriforme. Reassessment of myxozoans as metazoans reveals terminal
      differentiation, typical metazoan cellular junctions, and collagen production.
      Their "polar capsules" are redescribed as typical nematocysts bearing atrichous
      isorhiza. Insofar as taxa cannot be contained within other taxa of equal rank,
      the phylum Myxozoa is abandoned and it is recommended that the group as a whole
      be removed from all protistan classifications and placed in a more comprehensive
      cnidarian system.

PMID- 8544073
TI  - Kinetoplasts play an important role in the drug responses of Trypanosoma brucei.
AB  - Trypanosoma brucei E164 and a dyskinetoplastic derivative, Dysk164, were injected
      into mice that were treated subsequently with methylglyoxal-bis-guanylhydrazone,
      berenil, ethidium bromide, and acriflavine. Additionally, parasites were
      photoaffinity labeled with ethidium monoazide to effect covalent drug attachment
      prior to injection into animals. In all cases, killing of animals with E164 was
      blocked by the drug treatment, whereas killing due to Dysk164 was not. These
      findings are consistent with the view that the intact kinetoplast plays an
      essential role in the action of these drugs.

PMID- 8544075
TI  - Praziquantel treatment normalizes intestinal myoelectric alterations associated
      with Hymenolepis diminuta-infected rats.
AB  - Hymenolepis diminuta-associated alterations in rat intestinal myoelectric
      patterns are abolished following therapeutic administration of the anthelmintic
      praziquantel (PZQ). Host intestinal smooth muscle myoelectric patterns,
      reflecting smooth muscle contractility and intestinal phasic motility, were
      recorded using in vivo serosal electrodes, surgically implanted on the duodenum,
      jejunum, and ileum. Repeated electromyographic recording from unrestrained and
      unanesthetized rats began 5 days after electrode implantation surgery. Three
      initial control recordings from each rat confirmed the appearance of normal
      intestinal myoelectric patterns, characterized by the interdigestive migrating
      myoelectric complex (MMC). All animals were subsequently infected with H.
      diminuta and myoelectric recordings beginning after day 8 postinfection confirmed
      the appearance of diminished frequency of the MMC and 2 nonmigrating myoelectric
      patterns, i.e., repetitive bursts of action potentials and sustained spike
      potentials. PZQ was used to remove the tapeworms from rats 12 days after
      Hymenolepis diminuta infection, as intestinal myoelectric changes become maximal
      at this time in tapeworm-infected rats. PZQ administered to uninfected rats at
      either of 2 dose levels did not affect host interdigestive myoelectric activity.
      After removal of the parasite with PZQ, electromyographic recordings indicated a
      return to normal uninfected electrical patterns within 24 hr of drug treatment.
      We have demonstrated that the presence of Hymenolepis diminuta is necessary to
      induce and maintain abnormal intestinal myoelectric patterns. The altered motor
      properties of tapeworm-infected rat intestine and the rapid reconversion to
      preinfection myoelectric patterns provides a new and unique model to examine the
      regulatory mechanisms of intestinal motility and its control by luminal
      parasites.

PMID- 8544074
TI  - Activity of lytic peptides against intracellular Trypanosoma cruzi amastigotes in
      vitro and parasitemias in mice.
AB  - Three cecropin-like lytic peptides (DC-1, DC-2, and DC-2R) were synthesized with
      virtually no sequence homology with the natural compound (cecropin B) while
      retaining the charge distribution, amphipathic, and hydrophobic properties of the
      natural compound. A fourth analog (alpha-Pi) without these later properties, but
      a similar molecular weight, was also synthesized as a nonlytic peptide control.
      The 3 lytic peptides were examined for their ability to kill Trypanosoma cruzi
      trypomastigotes in vitro, intracellular amastigotes in vitro, and their toxicity
      to a mammalian cell line. DC-2 at 5 microM and DC-1 and DC-2R at 10 microM were
      100% effective in killing T. cruzi trypomastigotes in vitro, suggesting at least
      a 10-fold increase in lytic activity over previous tested lytic peptide
      analogues, SB-37 and Shiva-1. When T. cruzi-infected Vero cells were treated with
      a single or double exposure of low concentrations (2.5 microM) of DC-1, DC-2, and
      DC-2R there was a significant (P < 0.05) reduction in amastigote numbers/cell
      when compared to untreated and alpha-Pi-treated T. cruzi-infected cells. Vero
      cells alone treated with the lytic peptides showed no reduction in number or
      toxicity. One of the peptides (DC-1) was tested for its toxicity in AJ mice and
      its ability to reduce parasitemias in T. cruzi-infected AJ mice. No untoward
      effects were seen in AJ mice injected intravenously with 50 micrograms/mouse
      daily for 10 days. There was a significant (P < 0.05) reduction in parasitemia
      and mortality by day 14 postinoculation (from 100% to 0%) in T. cruzi-infected AJ
      mice given 25 micrograms of DC-1/mouse on days 2, 4, 6, 8, and 10
      postinoculation.

PMID- 8544076
TI  - Flow cytometric analysis of the response of Eimeria tenella (Coccidia)
      sporozoites to coccidiocidal effects of ionophores.
AB  - Fluorescein diacetate (FDA) and propidium iodide (PI) were used as indicators of
      membrane integrity after Eimeria tenella sporozoites were treated with polyether
      ionophores. Flow cytometry was used to quantitate the structural and functional
      effects based on red or green fluorescence and shape index of the sporozoites.
      Two field isolates (FS119 and FS139) were essentially resistant to polyether
      ionophores administered under practical conditions, whereas a laboratory strain
      was considered sensitive. The shape of sporozoites changed after treatment with
      ionophores, and this could be detected by flow cytometry. Green-fluorescing cells
      declined in number as the membranes were compromised by ionophore treatment. Red
      fluorescing cells increased as the compromised membranes allowed entry of PI to
      bind with the nucleic acids. These effects were generally slower to develop in
      ionophore-tolerant field isolates compared with the sensitive laboratory strain.
      The effect of lasalocid on FDA and PI uptake, change in shape of the sporozoites,
      and lysis of sporozoites was more rapid than that of monensin or salinomycin. The
      2 field isolates responded at different rates to salinomycin and monensin. Flow
      cytometry was a sensitive and accurate instrument for analysis of the effects of
      ionophores on sensitive and resistant lines of coccidia.

PMID- 8544077
TI  - Effects of calmodulin and protein kinase C antagonists on muscle in the filariid,
      Acanthocheilonema viteae.
AB  - Drugs that act on calmodulin and protein kinase C (PKC) were investigated in the
      filariid Acanthocheilonema viteae. The filariid was slit open longitudinally and
      attached to an isotonic muscle transducer in a warmed (37 C) chamber containing
      physiologic solution bubbled with 95% N2-5% CO2. The calmodulin inhibitors,
      trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide
      hydrochloride (W-7), increased the spontaneous contractions of the parasite at
      low concentrations and induced a contraction followed by a flaccid paralysis at
      high concentrations. Trifluoperazine and W-7 also reduced the contractions from
      acetylcholine (ACh) and KCl in a concentration-dependent manner. The phorbol
      esters, phorbol 12-myristate 13-acetate and phorbol 12, 13-dibutyrate, which
      activate PKC, were either inactive or only weakly active at inducing
      contractions. Staurosporine (10(-6) M), a PKC inhibitor, enhanced and then
      blocked the spontaneous contractions of the filariid. Two other PKC inhibitors, H
      7 (10(-4) M) and sphingosine (3 x 10(-5) M), induced much smaller increases in
      the spontaneous contractions and did not inhibit them. Staurosporine and
      sphingosine inhibited the ACh contractions; however, staurosporine only slightly
      reduced the maximal KCl contraction. These results support a role for calmodulin,
      but not for PKC, in filarial muscle contraction.

PMID- 8544078
TI  - Effect of fatty acid treatment in cerebral malaria-susceptible and nonsusceptible
      strains of mice.
AB  - Cerebral malaria-susceptible (C57BL/6) mice infected with Plasmodium berghei ANKA
      (PbA) developed low parasitemia and died from typical neurological symptoms
      between 8 to 10 days after infection. In contrast, nonsusceptible (BALB/c) mice
      developed high peripheral blood parasitemia and died 22-24 days later without
      neurological implications. Daily injections of fatty acids (FA) during the first
      3 days after infection protected C57BL/6 mice from cerebral symptoms but had no
      effect on BALB/c mice. Thus, treated C57BL/6 mice developed hyperparasitemia and
      died 25 days after infection, like BALB/c mice. Red blood cells from C57BL/6
      control mice were found to be more resistant to lysis by linoleic acid than those
      of BALB/c mice. Three days following infection with PbA, these differences
      disappeared. Treatment with FA prevented these changes. We concluded that the
      host's cells were altered soon after infection and that the nature and degree of
      alterations depended on the mouse strain, thus determining the eventual outcome
      of the infection. Likewise, the effects of FA might not be directed against the
      parasite but rather seem to act early after infection on these parasite-induced
      modifications of host cells.

PMID- 8544079
TI  - Isoenzyme profile of Paracoccidioides brasiliensis.
AB  - Isoenzyme profiles of 10 strains of Paracoccidioides brasiliensis from different
      origins (nine strains from patients with different clinical forms of
      paracoccidioidomycosis and one from the faeces of a penguin) were determined by
      polyacrylamide gel electrophoresis using 37 different enzymes. Differences in
      carbonate dehydratase, phosphoglucomutase, phosphoglucoseisomerase, glucose-6
      phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactate dehydrogenase
      and beta-esterase were detected among the isolates studied allowing the
      characterization of nine zymodemes. Two isolates showed identical profiles. There
      was no correlation between the zymodeme patterns and virulence, clinical forms of
      the disease nor age of the cultures.

PMID- 8544080
TI  - An exoantigen test for the rapid identification of medically significant Fusarium
      species.
AB  - The accurate identification of Fusarium species can take 2-3 weeks. Preliminary
      exoantigen studies indicate that a mature culture suspected of being a Fusarium
      species may be immunologically identified 48 h after receipt. Exoantigen extracts
      of 10-day-old slant cultures of Fusarium chlamydosporum, Fusarium moniliforme (=
      Fusarium verticilloides), Fusarium oxysporum, Fusarium proliferatum and Fusarium
      solani and partially purified reference homologous and heterologous shake culture
      extracts (6-week-old) were reacted against rabbit anti-F. chlamydosporum, F.
      moniliforme, F. oxysporum, F. proliferatum and F. solani sera, in a micro
      immunodiffusion procedure. The results indicated that all the strains belonging
      to a given species produced 1-3 bands of identity only when tested against its
      homologous antiserum and reference antigen. No cross-reactions were observed with
      the heterologous antisera. Furthermore, extracts from isolates of Fusarium
      dimerum, Fusarium equiseti, Fusarium roseum complex, Acremonium species,
      Cylindrocarpon, Fonsecaea pedrosoi and Trichoderma species did not react with any
      of the prepared Fusarium species' antisera. Our data suggest that the exoantigen
      procedure is a rapid and reliable tool for the accurate immuno-identification of
      the medically important Fusarium species studied.

PMID- 8544081
TI  - Cryptococcosis in dogs: a retrospective study of 20 consecutive cases.
AB  - The clinical and mycological findings in 20 consecutive cases of cryptococcosis
      evaluated between 1981 and 1995 were analysed retrospectively. Typically, young
      adult dogs (median age 2 years) of either sex were affected. Dobermann Pinschers
      and Great Danes were significantly over-represented in relation to other breeds
      and crossbred dogs, and there was no trend for cryptococcosis to be acquired at a
      particular time of year. Cryptococcus neoformans was cultured from 18 dogs, with
      16 isolates further characterized. Of these, C. neoformans var. neoformans was
      isolated from 12 cases, while the remaining four strains were C. neoformans var.
      gattii. Dogs with C. neoformans var. gattii infections resided in rural (two
      cases) or suburban (two cases) environments. Ten dogs were presented as a result
      of infection of structures inside, adjacent to, or contiguous with the nasal
      cavity. Seven dogs were presented primarily for signs of central nervous system
      disease, of which at least three also had cryptococcal rhinosinusitis. One dog
      had cryptococcal pneumonia and also possible mycotic rhinitis, another had
      disseminated disease with lymph node and skin involvement, while the last dog was
      presented for vomiting referable to cryptococcal mesenteric lymphadenitis.
      Treatment consisting of surgery and/or antifungal drug therapy was successful in
      the majority of animals in which it was attempted, including two of three cases
      with meningo-encephalitis.

PMID- 8544082
TI  - Phylogeny and dating of some pathogenic keratinophilic fungi using small subunit
      ribosomal RNA.
AB  - The phylogenetic relationship of representative members of the genera
      Trichophyton, Microsporum and Epidermophyton was studied. 844 base pairs were
      compared after sequencing the nuclear 18S ribosomal RNA gene spanning the most
      variable area within the central 600 bases of this gene. The dermatophytes, which
      are monophyletic in origin, could be classified most effectively when placed as a
      subgroup in the Onygenales, Ascomycotina. The calculated radiation time was about
      50 million years ago. The early cenozoic adaptive explosion of mammals, which can
      serve as a host for the keratinophilic fungi, provides corroboration for
      proximate co-evolution.

PMID- 8544083
TI  - Cryptococcosis in a North Island brown kiwi (Apteryx australis mantelli) in New
      Zealand.
AB  - A case of disseminated cryptococcosis in a North Island kiwi (Apteryx australis
      mantelli) caused by Cryptococcus neoformans var. gattii (serotype B) is reported.
      This is the first case of cryptococcosis to be reported in a kiwi and is also the
      first isolation of C. neoformans var. gattii from a veterinary source in New
      Zealand. The kiwi is an example of a ratite bird and as such has a lower body
      temperature approximating that of a mammal. As a consequence, the kiwi and other
      ratitis (e.g. emus) would be expected to show an increased susceptibility to
      cryptococcosis compared with other birds. There has been only one other isolate
      of this variety of C. neoformans in New Zealand and this was isolated from the
      sputum of a human male with leukaemia who was from the Gisborne area of the North
      Island, a region adjacent to Hawkes Bay where the case of kiwi cryptococcosis
      occurred. Some months prior to the development of the infection in the bird, a
      mulch of Eucalyptus leaves/twigs had been spread throughout the kiwi enclosure
      and this is considered to have been the probable source of the yeast. Neither
      Eucalyptus camaldulensis nor Eucalyptus tereticornis were among the species from
      which the mulch material originated and it is suggested another species may be
      the environmental host(s) of C. neoformans var. gattii in New Zealand.

PMID- 8544084
TI  - Efficacy of oral saperconazole in systemic murine aspergillosis.
AB  - Saperconazole is a fluorinated bis-triazole. Groups of ten 5-week-old female CD-1
      mice were infected intravenously with 5.5 x 10(7) Aspergillus conidia.
      Saperconazole, dissolved in hydroxypropyl-beta-cyclodextrin (HPBC), was given
      orally twice a day for 11 days, beginning 1 day post-infection, at 50, 100 or 200
      mg kg-1 day-1. At day 18 post-infection, survivors were killed and residual
      infection quantified in the kidneys. With Aspergillus fumigatus isolate 10AF, 70%
      given no therapy, 100% given daily oral HPBC and 40% given intraperitoneal
      amphotericin B at 3.3 mg kg-1 three times a week for 2 weeks died, whereas all
      mice given saperconazole survived. Each saperconazole regimen prolonged survival
      compared to untreated or HPBC treated mice (P < 0.01). Saperconazole at 200 mg kg
      1 day-1 reduced colony forming units of aspergillus in kidneys more than 1000
      fold compared to untreated or HPBC treated mice (P < 0.001) and saperconazole
      regimens were superior to amphotericin B therapy (P < 0.01). In another study of
      the same design with A. fumigatus isolate 15AF, 90% of untreated and 20% of mice
      treated with saperconazole at 50 mg kg-1 day-1 died; all others survived. Any
      saperconazole regimen prolonged survival (P < 0.001). Residual infection was also
      significantly reduced by all saperconazole regimens (P < 0.01). With Aspergillus
      terreus isolate 4AT, 80% of untreated mice, 50% of mice treated with
      saperconazole at 50 mg kg-1 day-1 and 10% of mice treated at 200 mg kg-1 day-1
      died. Any saperconazole regimen prolonged survival (P < 0.05). Saperconazole at
      100 and 200 mg kg-1 day-1 also reduced residual infection (P < 0.001). No adverse
      effects were noted in any study. Thus, saperconazole was efficacious in vivo
      against different Aspergillus isolates.

PMID- 8544085
TI  - Rapid detection and identification of pathogenic fungi by polymerase chain
      reaction amplification of large subunit ribosomal DNA.
AB  - We describe a polymerase chain reaction (PCR) based approach to the detection and
      identification of pathogenic fungi which has potential for the diagnosis of
      systemic mycoses. Primers to sequences of the large subunit ribosomal DNA genes,
      which are universally conserved within the fungal kingdom, were capable of
      amplifying DNA from 43 strains representing 20 species (12 genera) of medically
      important fungi. Sequence analysis of the products obtained from Aspergillus
      fumigatus, Candida albicans and Cryptococcus neoformans allowed us to design
      species-specific primers which only amplified homologous DNA. The use of these
      two PCRs in tandem allows the detection (universal PCR) and identification
      (species-specific PCR) of a fungal pathogen within 8 h from simulated clinical
      specimens.

PMID- 8544086
TI  - Phylogenetic relationships of human-pathogenic Cladosporium (Xylohypha) species
      inferred from partial LS rRNA sequences.
AB  - The controversy about the appropriate taxonomic placement of agents of
      subcutaneous and systemic mycoses in either Cladosporium or Xylohypha, both
      genera characterized by conidia being produced in dry, acropetal chains, was
      addressed with partial sequencing of LS ribosomal RNA. Observation of catenate
      anamorphs in species of Capronia (Ascomycotina, Herpotrichiellaceae), a genus
      which also has anamorphs in Exophiala, suggested the possibility of a close
      interrelationship of all human-associated taxa. To test this hypothesis, partial
      sequences of 43 strains of Cladosporium/Xylohypha were analysed. Human-pathogenic
      and saprophytic Cladosporium species were found to be phylogenetically distinct
      from each other and, on the basis of known teleomorph relationships, were
      considered to be anamorphs of Herpotrichiellaceae and Mycosphaerellaceae,
      respectively. They should therefore be classified in different anamorph-genera;
      Cladosporium being restricted to plant-associated species. A relatively large
      proportion of the Herpotrichiellaceae is presumed to be animal-associated. The
      black yeast genus Exophiala was also confirmed to be of herpotrichiellaceous
      relationship. The genus Xylohypha is unrelated.

PMID- 8544087
TI  - Nutritional physiology and taxonomy of human-pathogenic Cladosporium-Xylohypha
      species.
AB  - Physiological profiles of type, authentic and some additional isolates of
      Cladosporium-Xylohypha species of purported herpotrichiellaceous relationship are
      established. This group comprises melanized catenate hyphomycetes which are
      prevalently found on the human host. The species are excluded from the genus
      Cladosporium and are classified in the genus Cladophialophora. Taeniolella boppii
      is also transferred to this genus. Cladosporium bantianum (= Xylohypha emmonsii)
      and C. trichoides are considered conspecific and are now referred to as
      Cladophialophora bantiana. Meso-erythritol, L-arabinitol, ethanol and growth at
      40 degrees C are found to be the most useful criteria for species distinction.
      The species Cladosporium carrionii is found to be heterogeneous. The anamorph of
      the saprophytic ascomycete Capronia pilosella is morphologically similar to an
      authentic strain of Cladosporium carrionii, but physiologically distinct. A
      diagnostic key for the recognized Cladophialophora species and to morphologically
      similar taxa is provided.

PMID- 8544088
TI  - Systemic mycosis caused by a new Cladophialophora species.
AB  - A 22-year-old woman suffered from haemoptyses of unknown aetiology. A tumour in
      the lingula was diagnosed histologically to be a granulomatosis, most likely a
      sarcoidosis. Two years later, the patient returned with dyspnoea caused by a
      granulomatous tumour in the trachea, histologically similar to that seen earlier.
      After bronchoscopic laser resection, cortisone therapy was applied but without
      success. A fungus was subsequently discovered histologically and was cultivated
      from biopsy specimens. Retrospective research of primary histological slides led
      to the conclusion that a mycosis was the initial cause of the tumours. The
      mycosis was successfully treated with high-dose itraconazole for 1 year, combined
      with 5-fluorocytosine (5-FC) during the first few months. The causative agent was
      found to be a new species of Cladophialophora, and is described as C. arxii
      Tintelnot; its key characteristics are presented.

PMID- 8544089
TI  - A human isolate of Exophiala (Wangiella) dermatitidis forming a catenate
      synanamorph that links the genera Exophiala and Cladophialophora.
AB  - A strain of the black yeast Exophiala dermatitidis displayed a hydrophobic
      synanamorph consisting of acropetal chains of lemon-shaped conidia,
      morphologically similar to those of Cladophialophora bantiana. The occurrence of
      the two conidial types in a single strain suggests a taxonomic affinity between
      Exophiala and Cladophialophora and provides support to the supposition that
      Cladophialophora, a possible anamorph genus of Herpotrichiellaceae, is related to
      black yeasts rather than to Cladosporium, which has teleomorphs in the
      Mycosphaerellaceae.

PMID- 8544090
TI  - Keratitis due to Cephaliophora irregularis Thaxter.
AB  - The second case of mycotic keratitis due to Cephaliophora irregularis is reported
      in a 55-year-old female from India. Clinically this fungus was resistant to
      treatment with oral ketoconazole but responded to topical natamycin.

PMID- 8544091
TI  - Characterization, in vitro and in vivo studies on primaquine diphosphate
      liposomes.
AB  - In this study, several Primaquine diphosphate (PQ) liposomal formulations
      containing phospholipid, charge inducer and with or without cholesterol in molar
      ratios of 7:1:(2) and 10:1:(4) were investigated. Gel state (DPPC:CHEMS:CHOL and
      PL-100H:CHEMS:CHOL) and liquid-crystalline state (PL-100:CHEMS:CHOL and PL
      90G:CHEMS:CHOL) liposomes were prepared. The film method followed by sonication
      and extrusion through polycarbonate membrane was used. Particle size
      distribution, percentage of entrapped active substance, content of phospholipid
      and bilayer type and composition were determined. Lamellarity was determined by
      31P-NMR technique. In vitro release of PQ was investigated at 37 degrees C, 35
      rpm and in Tris (pH: 7.4) buffer. In vitro release and its fit to kinetic models
      were investigated. Liposomes were labelled by 99mTc and injected intravenously to
      Swiss Albino mice.

PMID- 8544092
TI  - Enhanced in vivo performance of liposomal indomethacin derived from effervescent
      granule based proliposomes.
AB  - Indomethacin, a non-steroidal anti-inflammatory drug was successfully entrapped
      into liposomes (soyabean lecithin, cholesterol, stearylamine or dicetylphosphate)
      with uniform size distribution. The liposomal vesicles were derived from dried
      effervescent granule-based proliposomes. The in vivo distribution characteristics
      of the reconstituted liposomal indomethacin was studied in normal rats and in the
      rats with inflamed paws following intravenous administration. The localization of
      the liposome-based indomethacin was in liver, lungs and inflamed tissues
      (inflamed rats studies). Further, an enhanced anti-inflammatory activity of lipo
      indomethacin was found as compared with the activity recorded for plain drug in
      carrageenan induced paw oedema in rats.

PMID- 8544093
TI  - Microencapsulation of lobster carotenoids within poly(vinyl alcohol) and poly(D,L
      lactic acid) membranes.
AB  - The use of natural pigments such as lobster carotenoids in fish feed formulations
      offers advantages over the use of the synthetic alternatives. Microencapsulation
      of the pigments, with or without the addition of antioxidants to the formulation,
      may be of benefit in terms of stabilizing pigment colour. In the present study,
      lobster carotenoids were extracted from lobster shell into petroleum ether and
      microencapsulated by phase separation and salt coacervation within (poly vinyl
      alcohol) and poly(vinyl alcohol)/poly(D,L-lactic acid) membranes. Spherical
      microcapsules, with smooth, thin and resilient membranes were obtained with mean
      diameters ranging from 50 to 150 microns, depending on the membrane material, and
      source of pigment. The microcapsules were pink-orange in colour, and colour
      stability was followed spectrophotometrically. Enhanced stability was observed in
      both membrane materials, in comparison to the non-encapsulated control. Rates of
      discoloration were determined under a variety of storage conditions, including
      the absence of light, reduced temperatures and under nitrogen atmosphere. The
      best stability of lobster carotenoids was observed under a nitrogen atmosphere
      within PVA/PLA membranes, representing an 11-fold enhancement of pigment
      stability in comparison to the controls. Under ambient conditions, the
      enhancement in pigment stability was approximately 6-fold. The optimum
      concentration of PVA during microencapsulation was 3-4%, and the
      microencapsulated pigments appeared most stable under acidic conditions. The rate
      of discoloration appeared independent of pigment concentration.

PMID- 8544094
TI  - Coating charcoal with polyacrylate-polymethacrylate copolymer for haemoperfusion.
      III: The effect of the coat thickness on the adsorptioncapacity of the coated
      charcoal and its adsorptivity to small and middle size molecules.
AB  - In this study, the effect of the coat thickness of polyacrylate-polymethacrylate
      copolymer on the adsorption capacity of activated charcoal to methylene blue as a
      model marker was investigated by constructing both Langmuir and Freundlich
      isotherms. It was found that the coat thickness significantly affected the
      adsorption coefficient of the coated charcoal to methylene blue as is reflected
      by the attractive forces between the adsorbent and the adsorbate. This effect is
      understandable as the membrane will act as a barrier between the adsorbent and
      the adsorbate. The coat thickness also had some effect on the adsorption capacity
      of activated charcoal but not as much as it affected the adsorption coefficient.
      The data followed the Freundlich isotherm more closely than the Langmuir
      equation. The effect of the coat thickness on the adsorption of selected drugs of
      different molecular size was also investigated using theophylline, paracetamol,
      sodium phenobarbital, creatinine and vitamin B12 as model drugs. The results
      showed that the adsorption patterns of theophylline, paracetamol and sodium
      phenobarbital were more or less similar. The apparent coating thickness did not
      affect the extent of adsorption of these model drugs and there was little effect
      on the adsorption rate especially during the first 15 min. The adsorption of
      vitamin B12 and creatinine showed completely different patterns which are
      discussed in detail.

PMID- 8544095
TI  - Control of mosquito larvae by encapsulated pathogen Bacillus thuringiensis var.
      israelensis.
AB  - Bacillus thuringiensis var. israelensis (B.t.i.) containing alginate
      microcapsules were prepared in order to maintain durable formulations which could
      resist several effects causing reduced efficiency during applications. B.t.i.
      spores were harvested through NYSM agar plates and encapsulated in Ca-alginate
      (0.5-2.0% w/v) gels without any significant loss of sporal or larvicidal
      activity. The effect of acidic pH on the larvicidal toxin was tested using Culex
      sp. larvae in the laboratory. The alginate microcapsules pretreated with
      saturated KH2PO4 solution gave larvicidal activity after 24-48 h, by bioassay.
      Suspension and encapsulated forms of the pathogenic bacterium were exposed to pH
      variations (3.0-10.0), UV light and high temperature (50 degrees C). Durability
      to Pb++, Cu++, Fe++ compounds and phenol was also examined. As the alginate
      content increased, stability of B.t.i. drastically increased against the tested
      effects, but to obtain useful releasing microcapsules, 1.0-1.5% w/v alginate
      concentrations were found to be optimum.

PMID- 8544096
TI  - Physical stability of different liposome compositions obtained by extrusion
      method.
AB  - Six different liposome compositions were evaluated according their physical
      stability. The compositions used were (in mole ratio):
      dipalmitoylphosphatidylcholine (DPPC): DPPC:cholesterol (CHOL) (1:1), DPPC:CHOL
      (1:6:1), DPPC:CHOL:sphingomyelin (SFM) (7:2:1), DPPC:CHOL:stearylamine (STE)
      (8:5:1) and DPPC:CHOL:dicetyl phosphate (DCP) (8:5:1). The liposomes were
      obtained by the extrusion method, through polycarbonate membranes of 0.1 micron
      pore size. The captured volume, number of lamellae, size and polydispersity of
      the vesicle populations were determined for all compositions. The physical
      stability was checked at -20 degrees C, room temperature, 4 degrees C and 50
      degrees C by determining the changes in vesicle size over a maximum of 40 days.
      The process of aggregation and/or fusion was observed by photon correlation
      spectroscopy. From the results, we can establish that the above compositions are
      metastable at a temperature of 50 degrees C. On the other hand, values of
      captured volume were smaller than predicted by theory. This fact can be explained
      by the non-sphericity of extruded vesicles. In relation to the stability, the
      introduction of CHOL in the formulation allows keeping the vesicles at 4 degrees
      C. In contrast, liposomes containing only DPPC are very stable at room
      temperature. Compositions with a high stability are those that have present SFM
      or STE. The latter keeps the structural bilayer at temperatures < 0 degrees C
      without cryoprotectors. Both the lipids, STE and DCP, form vesicles with a higher
      number of lamellae.

PMID- 8544097
TI  - Microencapsulation of O/W emulsions by formation of a protein-surfactant
      insoluble complex.
AB  - A method for obtaining microcapsules of oil droplets by the formation of an
      insoluble complex of protein-surfactant is described. The gelatin type A studied,
      which is positively charged at the pH range studied, may form insoluble and
      soluble complexes with sodium dodecyl sulphate (SDS), an anionic surfactant. The
      binding isotherms were studied and the specific molar ratios of SDS to gelatin,
      in which the insoluble complex is formed, was determined. These specific ratios
      also led to the formation of microcapsules, in which the wall encapsulating the
      oil droplets, is composed of the insoluble gelatin SDS complex.

PMID- 8544098
TI  - Development of digoxin dry elixir as a novel dosage form using a spray-drying
      technique.
AB  - A rapidly absorbed new novel oral dosage form for digoxin termed 'digoxin dry
      elixir' was developed by the spray-drying technique. Digoxin, dextrin and sodium
      lauryl sulphate were dissolved in a ethanol-water mixture (20:25 w/w) and
      therefore spray-dried to form the digoxin dry elixir. According to scanning
      electron micrographs, digoxin dry elixir is spherical in shape with a smooth
      surface. The geometric mean diameter of dry elixir determined by laser particle
      size analysis was about 13 microns. The appearance and flow properties were
      almost unchanged and about 10% of ethanol contents in the dry elixir decreased
      during 180 days in a sealed bottle at room temperature. Comparative studies on
      the in vitro dissolution and in vivo absorption of digoxin in the form of digoxin
      dry elixir, digoxin elixir and digoxin powder were carried out. Digoxin in the
      dry elixirs was completely dissolved within 2 min. On the other hand, only about
      87% of digoxin powder dissolved in 60 min. The initial dissolution rates of
      digoxin in the dry elixirs markedly increased in distilled water at 37 degrees C,
      which were over 100 fold higher than that of digoxin powder alone. The maximal
      plasma concentration of digoxin (Cmax) and area under the digoxin concentration
      time curve from zero to 6 h (AUC0-6h) after the oral administration of digoxin
      dry elixir were almost 3.8 and 5.5 fold increased compared to digoxin powder
      alone. No significant difference of AUC0-6 h between dry elixir and elixir was
      observed, but the Cmax of digoxin in the form of dry elixir was significantly
      reduced compared to the digoxin elixir (0.57 versus 0.83). Digoxin dry elixir
      might be a useful solid dosage form to improve the dissolution rate and
      bioavailability of poorly water-soluble digoxin compared to digoxin powder alone.
      It also indicates that dry elixir might reduce the side effects in oral digitalis
      glycoside therapy compared to the digoxin elixir due to the reduction of Cmax.

PMID- 8544099
TI  - The microencapsulation of protein using a novel ternary blend based on
      poly(epsilon-caprolactone).
AB  - Microspheres with an entrapped protein were prepared from poly(epsilon
      caprolactone) (PCL), and a novel ternary blend, comprising of high and low
      molecular weight PCL in combination with poloxamer 181, a triblock copolymer of
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide). The inclusion of
      low molecular weight PCL served to enhance phase mixing by a reduction in the
      molecular weight of the polymeric components. Encapsulation of the protein,
      bovine serum albumin, was possible using a water-in-oil-in-water multiple
      emulsion solvent evaporation technique. Microspheres prepared from unblended PCL
      were irregular and porous in nature. The presence of surface imperfections and
      macroscopic pores was attributable to the high rate of crystallization of the PCL
      polymer from solution. The inclusion of poloxamer 181 into the matrix retarded
      the rate of crystallization of the PCL, thereby enhancing particulate sphericity
      and regularity. Manipulation of the process parameters of blended microspheres
      provided a means of controlling the particle size and the entrapment efficiency
      of the protein. The influence of variables such as protein to polymer ratio,
      internal phase volume and emulsifier concentration in both the internal and
      external aqueous phases, on the properties of the microspheres was investigated.
      A mean particle size ranging from 10 to 42 microns could be achieved by altering
      the internal phase volume of the primary emulsion, whilst a high protein
      entrapment (11% w/w) was possible with a protein to polymer ratio of 1:4. Native
      PAGE analysis of the entrapped protein indicated a maintenance of bulk structural
      integrity.

PMID- 8544100
TI  - Differential reactivity of anti-E-selectin monoclonal antibodies in human
      gingival tissue.
AB  - E-selectin is a cytokine-inducible endothelial glycoprotein which participates in
      the binding of leukocytes to vascular endothelium. Variable levels of expression
      of E-selectin have been reported in gingivitis and periodontitis, and two
      differing concepts of its significance have emerged: either gingival blood
      vessels express E-selectin constitutively, or are continuously activated by
      inflammatory mediators arising from the gingival environment. A range of
      monoclonal antibodies reacting with different epitopes of E-selectin are
      available commercially. The present study explored the possibility that the
      choice of antibody could affect estimation of the level of expression of E
      selectin in vivo. Five monoclonal antibodies were used to investigate E-selectin
      expression in serial cryosections of human gingival tissue. While E-selectin
      positive vascular endothelial cells were detected with all antibodies, the number
      of positively staining endothelial cells varied, with BBA1 > H4/18 = H18/7 = 4D10
      > 1.2B6. The frequency of strong staining in tissue specimens was BBA1 > 4D10 >
      H4/18 = H18/7 > 1.2B6, while the frequency of weak staining showed the reverse
      trend. Additionally, with antibodies H18/7 and 1.2B6, 17 and 36% of the specimens
      were E-selectin negative. The occurrence of what appear to be false positives and
      false negatives confounds estimation of the level of E-selectin expression. Based
      on these findings, patterns of endothelial E-selectin expression in gingivitis
      and periodontitis should be re-evaluated.

PMID- 8544101
TI  - Synthesis of proinflammatory cytokines by human gingival fibroblasts in response
      to lipopolysaccharides and interleukin-1 beta.
AB  - We have examined the ability of gingival fibroblasts (GF) to participate in
      inflammatory response and function as accessory immune cells. The accessory
      immune function of GF cells was evaluated by their ability to elaborate
      proinflammatory cytokines following stimulation with lipopolysaccharides and
      interleukin-1 beta (IL-1 beta). Using three separate clonally derived and
      characterized human gingival fibroblast (GF) cell lines, we demonstrate that LPS
      from Actinobacillus actinomycetemcomitans (Aa) and Escherichia coli (Ec) induce
      mRNA and synthesis of proinflammatory cytokines, IL-1 beta, IL-6 and IL-8. IL-1
      beta activation of GF cells showed that IL-1 beta non only induces the expression
      of IL-6, IL-8 and TNF-alpha, but also acts in an autocrine manner of GF cells and
      induces IL-1 beta expression. Furthermore, the continuous presence of IL-1 beta
      in GF cell cultures did not down regulate the response of GF cells to IL-1 beta.
      Pretreatment of GF cells with IL-1 beta resulted in the enhanced synthesis of TNF
      alpha in response to additional IL-1 beta. These findings indicate that GF cells,
      in addition to providing structural support, may also function as accessory
      immune cells and play an important role in the initial inflammatory reaction as
      well as in the amplification of immune response.

PMID- 8544102
TI  - Competition for peptides and amino acids among periodontal bacteria.
AB  - We recently studied the utilization of glutathione (L-gamma-glutamyl-L
      cysteinylglycine), L-cysteinylglycine and L-cysteine by anaerobic bacteria. The
      rate of hydrogen sulfide formation from these compounds was determined and it was
      concluded that Peptostreptococcus micros and Fusobacterium nucleatum subsp.
      nucleatum had an active transport of small peptides. In the present study it is
      shown that methyl mercaptan formation from L-methionine and L-methionyl
      containing peptides can also be used to study peptide utilization. There were
      differences among the periodontal bacteria P. micros, F. nucleatum subsp.
      nucleatum, and Porphyromonas gingivalis in their capacity to use L-cysteine and L
      methionine and peptides containing these amino acids. The peptides were used more
      efficiently by P. micros and F. nucleatum subsp. nucleatum than by P. gingivalis.
      All three species used the peptides more efficiently than the free amino acids.
      The efficiency in utilizing various amino acids and peptides may be among the key
      determinants of the periodontal microbial ecology.

PMID- 8544104
TI  - Periodontitis in the baboon: a potential model for human disease.
AB  - Advances in periodontics with respect to disease activity, microbiology and
      immunology have demonstrated the multifactorial nature of periodontal diseases.
      This serves to underscore the need for an ideal animal model for periodontal
      research. Non-human primates are most similar to man in comparison to other
      animal models. The baboon is an Old World monkey that has infrequently been used
      in periodontal research. Periodontal exams were accomplished on 116 baboons
      (Papio anubis, P. cynocephalus) ages 5 to 30 years with one baboon year being
      roughly equivalent to 3 to 4 human years. The study population consisted of 29
      males and 87 females. Clinical parameters including probing depth, attachment
      level, mobility, plaque index and gingival index were collected. Radiographs were
      taken on 25 animals and correlated to clinical findings. Results showed a
      significant increase in mean probing depth and mean attachment level with age (p
      = 0.0001). Disease prevalence and severity were not significantly different
      between genders. Mobility was uncommon; however, the prevalence and severity of
      furcation involvement increased with age. Radiographs suggested horizontal and
      isolated vertical bone loss. Plaque and gingival indices were at sustained high
      levels for all age groups and showed a statistically significant increase with
      age. Some baboons were found to develop a naturally-occurring periodontitis that
      increased in severity with age. This primate may be a suitable model for studies
      in human periodontal disease.

PMID- 8544103
TI  - Reactive antibodies in sera from pubertal and adult gingivitis patients against
      various Porphyromonas gingivalis antigens.
AB  - This study was undertaken to determine the immunodominant antigens from
      Porphyromonas gingivalis which reacted with sera from patients of pubertal and
      adult gingivitis. The patients with cultivable P. gingivalis and the patients
      without cultivable P. gingivalis were compared by immunoblots. Fifty subjects
      participated in this study: 20 with gingivitis, 20 periodontally healthy, and 10
      with adult periodontitis. The groups with gingivitis and healthy periodontium
      each contained 10 pubescent subjects and 10 adult subjects. P. gingivalis was
      isolated from 9 of 20 patients with gingivitis and from all of 10 with
      periodontitis by culture study. Approximate molecular weight 43 KDa fimbriae
      antigen, 57, 53, 46, 28 KDa antigens from outer membrane, and 57, 44, 40, 18.5
      KDa antigens from sonicated extracts of P. gingivalis reacted significantly more
      frequently with sera from the P. gingivalis culture-positive gingivitis patients
      than with sera from the culture-negative patients by Fisher's exact test. A
      molecular weight 75, 31 KDa antigen from outer membrane and a 46 KDa antigen from
      sonicated extract were immunodominant in sera from adult patients with
      periodontitis. These findings indicate that the specific antigens which reacted
      with sera from P. gingivalis culture-positive patients are markers of infection
      with P. gingivalis. Additionally, reactivity to antigens were slightly different
      between sera from patients with gingivitis and those from patients with
      periodontitis.

PMID- 8544105
TI  - Changes in periodontal treatment needs. A follow-up study of Oslo citizens from
      the ages of 35 to 50 years.
AB  - A random sample of 35-year-old subjects from Oslo took part in a dental survey in
      1973 and were re-examined in 1988. Eighty-one subjects (85%) attended the final
      examination. The need for periodontal treatment was assessed by the Periodontal
      Treatment Need System (PTNS), and the oral hygiene by the Simplified Oral Hygiene
      Index (OHI-S). The participants attended a structured interview and answered a
      questionnaire about general and dental health habits as well as psycho-social
      factors. Only small changes in the distribution of subjects in the different PTNS
      categories were found to have taken place during the 15 years. In 1973, 56.8%
      were in need of scaling (Class B) and 32.1% had one or more deep inflamed pockets
      (Class C), and in 1988 the scores were 54.3% and 30.1% respectively. A logistic
      regression model was used to study the associations between risk factors and
      increased treatment need, as expressed by increase in the number of C-quadrants.
      Increased number of C-quadrants was positively associated both with short
      duration of education and with no interdental cleaning. Using a socio-ecological
      model for periodontal diseases, variables describing the items "behaviour" and
      "environment" were found to be most closely associated with increased need for
      periodontal treatment.

PMID- 8544106
TI  - Temperate bacteriophages are common among Actinobacillus actinomycetemcomitans
      isolates from periodontal pockets.
AB  - Actinobacillus actinomycetemcomitans is a suspected etiologic agent in
      destructive periodontal diseases. The detection of bacteriophages in A.
      actinomycetemcomitans in the subgingival plaque of patients with rapidly
      destructive forms of periodontitis led to the hypothesis that bacteriophage
      infection might increase the virulence of this bacterium (19). A.
      actinomycetemcomitans was isolated from 68 subjects from the Netherlands and
      Switzerland with localized juvenile periodontitis, rapidly progressing
      periodontitis, or adult periodontitis, and was tested for the presence of
      temperate bacteriophage with the overlay plate technique. More than half of the
      A. actinomycetemcomitans strains were found to release bacteriophage which formed
      individual plaques on indicator strains. Electron microscopy of preparations from
      7 strains revealed virions with an icosahedral head and a contractile tail
      typical for double-stranded DNA bacteriophages. The presence of A.
      actinomycetemcomitans carrying temperate bacteriophage was not correlated with
      the composition of the subgingival microflora nor with the clinical form of
      periodontal disease. Destructive periodontal disease of subjects with phage
      carrying A. actinomycetemcomitans was not more severe than of subjects with phage
      free A. actinomycetemcomitans as determined by several clinical parameters. In
      contrast, the pocket depth and the attachment loss were significantly lower for
      adult periodontitis subjects with phage-carrying A. actinomycetemcomitans. It
      seems unlikely that the frequently occurring temperate bacteriophages increase
      significantly the virulence of A. actinomycetemcomitans.

PMID- 8544107
TI  - ICAM-1-expressing pocket epithelium, LFA-1-expressing T cells in gingival tissue
      and gingival crevicular fluid as features characterizing inflammatory cell
      invasion and exudation in adult periodontitis.
AB  - Activated T lymphocytes constitute a major component of inflammatory cells in the
      early periodontal lesion, and also appear in the gingival crevicular fluid. In an
      attempt to clarify the relationship between the ICAM-1 (CD54) expression of
      pocket epithelium in gingiva and the infiltrating lymphocyte population, we
      carried out an analysis of CD11a+(LFA-1 alpha), CD25+(IL-2R alpha) and CD4+(Th)
      cells subjacent to ICAM-1-expressing pocket epithelia and CD11a+CD25+CD4+ cells
      in gingival crevicular fluid (GCF). GCF was collected by crevicular washing from
      16 patients with periodontitis (P group) and 3 subjects with healthy gingiva (H
      group). Peripheral blood (PB) was collected at the same time. Mononuclear cells
      were isolated by Ficoll-paque gradient centrifugation from GCF and PB. Monoclonal
      antibodies (mAb) to CD11a, CD25, and CD4 were used for three-color flow
      cytometry. Gingival biopsies were obtained from 7 patients in P group and 3
      subjects in H group. Serial cryostat sections (6 microns in thickness) were
      prepared from each biopsy, on which a double staining was performed. The number
      of CD11a+CD25+CD4+ cells and the fluorescence intensity of FITC conjugated anti
      CD11a were significantly higher in GCF than in PB (p < 0.001 to p < 0.01).
      CD11a+CD25+CD4+ cells were not detected in GCF in H group. The pocket epithelia
      expressed CD54 in P group, but not in H group. The number of CD11a+, CD25+ and
      CD4+ cells infiltrating the connective tissue subjacent to the upper, middle and
      lower parts of the CD54 positive pocket epithelium (n = 16) was 141 +/- 26, 38 +/
      13, 144 +/- 29 (cells/0.04 mm2), respectively, whereas in the CD54 negative
      pocket epithelium, it was (n = 5) 9 +/- 2, 3 +/- 1, 8 +/- 3. In P group, the
      CD11a+CD25+CD4+ cell number in GCF correlated with CD25+, CD11a+ cells in the
      connective tissue subjacent to the CD54+ pocket epithelium. These results
      indicate that expression of ICAM-1 in pocket epithelium is relevant to the
      migration of CD11a, CD25, CD4 positive cells in connective tissue subjacent to
      the pocket epithelium into the periodontal pocket. Assessing the relationship of
      our findings and other adhesion molecules would offer important clues to the
      understanding of T cell migration in affected gingiva.

PMID- 8544108
TI  - Elevated conversion of alpha-2-macroglobulin to the complexed form in gingival
      crevicular fluid from adult periodontitis patients.
AB  - The broad spectrum protease inhibitor, alpha 2-macgrolobulin (alpha 2M), is one
      of the host's principal regulators of both endogenous and exogenous proteases and
      is likely to have an important role in the regulation of proteolytic activity at
      inflammatory sites. We have determined the amount of complexed (com alpha 2M) and
      total alpha 2M (tot alpha 2M) in gingival crevicular fluid (GCF) harvested from
      shallow and deep sites in adult periodontitis (AP) patients (n = 21). An ELISA
      technique was developed to measure both forms of alpha 2M in the same sample
      utilizing a monoclonal antibody (MAb) specific for the complexed form. In
      addition, protease activity towards human serum albumin (Prot1), transferrin
      (Prot2) and N alpha-benzoyl-L-arginine 7-amido-4-methylcoumarin-hydrochloride
      (BAAMc; Prot3) were determined in a second GCF sample from the same site. Plasma
      alpha 2M concentrations were only positively correlated (p = 0.0163) with GCF tot
      alpha 2M from highly inflamed sites. We observed a significant positive
      correlation between tot alpha 2M and proteolytic activity in GCF from deep sites
      but not from shallow sites (Prot1: p = 0.002; Prot2: p = 0.005). A similar
      correlation between tot alpha 2M and proteolytic activity was found at highly
      inflamed sites (Prot1: p = 0.014; Prot2: p = 0.002). A very high proportion of
      the tot alpha 2M in GCF was in the complexed form at both shallow (71.14% +/-
      29.13) and deep sites (68.17% +/- 28.5) Com alpha 2M was positively correlated
      with proteolytic activity only in deep sites (Prot1: p = 0.015; Prot2: p =
      0.031). Our results suggest that the concentration of tot alpha 2M in the
      gingival crevice is positively associated with the amount of proteolytic activity
      at the site and that protease activities in GCF may only partly explain the high
      percentage conversion alpha 2M to the complexed form. The high level of alpha 2M
      inactivation in GCF from AP patients reported here may have significance not only
      in view of its role as a broad spectrum protease inhibitor but also through the
      differential effects of native vs complexed alpha 2M on the regulation of immune
      responses.

PMID- 8544109
TI  - Taking stock.

PMID- 8544110
TI  - Child rearing beliefs in the African-American community: implications for
      culturally competent pediatric care.
AB  - Cultural competence is increasingly acknowledged as an essential component of
      nursing care within the heterogeneous society our nation has become. A necessary
      antecedent to competence is an understanding of, and respect for, the beliefs and
      priorities of the families being served. Literature from a variety of disciplines
      in the areas of attachment, socialization agendas, discipline, and parental
      teaching is reviewed to provide a description of the cultural context for child
      rearing in African-American families. Implications for clinical practice are
      discussed.

PMID- 8544111
TI  - Illness characteristics and psychosocial and demographic correlates of illness
      severity at onset of insulin-dependent diabetes mellitus among school-age
      children.
AB  - To verify empirically the most prevalent physical signs and symptoms of diabetes
      at onset among school-age children, document the distribution of illness
      severity, and examine psychosocial and demographic correlates of initial illness
      severity, the authors analyzed data on 95 school-age children whose diabetes had
      been newly diagnosed. The most common presenting symptoms were generally
      consistent with descriptions in the clinical literature. Only 22% of the children
      presented with severe illness on admission. Children who lived in single-parent
      households tended to be more ill on admission than children who lived in two
      parent households.

PMID- 8544112
TI  - Oxygen saturations during breast and bottle feedings in infants with congenital
      heart disease.
AB  - Bottle feeding is commonly advised for infants with congenital heart disease
      (CHD) based on the belief that breast feeding is too difficult for them. However,
      studies of preterm infants have shown that greater cardiorespiratory effort
      occurs during bottle feeding than during breast feeding. The purpose of this
      study is to determine if there is a relationship between feeding method (breast
      vs. bottle) and oxygen saturations (SaO2) in infants with CHD. In a correlational
      design, pulse oximetry measured SaO2 during one breast and one bottle feeding in
      each of 7 infants with CHD. SaO2 during breast feeding is significantly different
      from SaO2 during bottle feeding (F = 59.72, p < .0001). SaO2 during breast
      feeding is higher on average and less variable (M = 96.3%, SD = 2.2) than SaO2
      during bottle feedings (M = 92.5%, SD = 6.9), indicating that there is less
      cardiorespiratory stress with breast feeding. None of the infants desaturated
      (SaO2 < 90%) during breast feedings, whereas four infants desaturated during
      bottle feedings.

PMID- 8544113
TI  - Effect of imagery on children's pain and anxiety during cardiac catheterization.
AB  - Children who undergo cardiac catheterization present pain management challenges
      to nurses. In this experimental study, the investigator examined the effect of
      imagery on children's pain and anxiety during cardiac catheterization. Twenty
      four children, aged 9 to 17 years were randomly assigned to a control, presence,
      or imagery condition. Physiological, psychological, and behavioral data were used
      to rate children's pain and anxiety during cardiac catheterization. Children in
      the imagery condition displayed fewer distress behaviors during cardiac
      catheterization. Children in the presence condition reported the lowest levels of
      pain. Cortisol elevation over baseline was lowest in the control group, a result
      consistent with findings in previous studies. Several correlations of interest
      are reported. Implications for nursing practice and research are discussed.

PMID- 8544114
TI  - Case study of the home health management of a child with congenital anomalies
      associated with prenatal cocaine abuse.
AB  - The presence of a history of poor parental upbringing, poverty, and substance
      abuse within a family stresses its capacity to cope with the needs of a child
      with congenital anomalies. Nursing has a key role to play in providing specific
      information, practical assistance, and support in these circumstances. A case
      study of a child in such a family is presented in this article, and the multiple
      nursing interventions provided to facilitate the family's coping skills are
      discussed.

PMID- 8544115
TI  - Family research: consideration of who to study.

PMID- 8544116
TI  - Pediatric trauma care.

PMID- 8544117
TI  - Effective use of computer systems.

PMID- 8544118
TI  - The role of support group facilitator: ensuring success.

PMID- 8544119
TI  - Child health and pediatric nursing in the Kingdom of Lesotho.

PMID- 8544120
TI  - Control of the amiloride-sensitive Na+ current in mouse salivary ducts by
      intracellular anions is mediated by a G protein.
AB  - 1. We have previously reported that the Na+ conductance in mouse intralobular
      salivary duct cells is controlled by cytosolic anions, being inhibited by high
      cytosolic concentrations of Cl- and NO3- but not of glutamate. In the present
      paper, we use whole-cell patch-clamp methods to investigate whether this anion
      effect is mediated by a G protein. 2. Inclusion of 100 mumol l-1 GTP-gamma-S, a
      non-hydrolysable GTP analogue, in the glutamate-containing pipette solution, i.e.
      when the Na+ conductance is active, reduced the size of the Na+ conductance
      whereas inclusion of 100 mumol l-1 GDP-beta-S, a non-hydrolysable GDP analogue,
      had no effect. 3. Inclusion of 100 mumol l-1 GDP-beta-S in the NO3(-)-containing
      pipette solution, i.e. when the Na+ conductance is inhibited, reactivated the
      conductance. Inclusion of 500 ng ml-1 activated pertussis toxin in the NO3(-)
      containing pipette solution had a similar effect on the Na+ conductance. 4. We
      conclude that the inhibitory effect of intracellular anions such as NO3- and Cl-
      on the amiloride-sensitive Na+ conductance in mouse mandibular intralobular duct
      cells is mediated by a G protein sensitive to pertussis toxin.

PMID- 8544121
TI  - A slowly activating Ca(2+)-dependent K+ current that plays a role in termination
      of swimming in Xenopus embryos.
AB  - 1. Acutely isolated Xenopus spinal neurons possess a slowly activating Ca(2+)
      dependent outward current which was revealed either by removal of external Ca2+
      or by the addition of the Ca2+ channel blocker, 150 microM Cd2+. 2. The Ca(2+)
      sensitive current was very slow to activate and had a mean time constant of
      activation of 437 ms at 0 mV. The current also had very long tail currents which
      were blocked by Cd2+. The rate of decay of the slowest component of the Ca(2+)
      dependent tail currents was insensitive to membrane potential suggesting that the
      relaxation of the Ca(2+)-dependent current may only be weakly voltage dependent.
      3. The reversal potential of the Ca(2+)-sensitive tail currents depended on the
      concentration of external K+ in a manner predicted by the Nernst equation. Thus
      the Ca(2+)-sensitive current was carried by K+. 4. The toxin apamin (10 nM to 2
      microM) selectively blocked the Ca(2+)-dependent K+ current without affecting
      voltage-gated K+ currents. This current may be analogous to a small-conductance
      Ca(2+)-dependent K+ (SK) current; however, unlike some SK currents, the Ca(2+)
      dependent K+ current was also sensitive to 500 microM tetraethylammonium chloride
      (TEA). 5. Applications of 10 nM apamin to spinalized embryos did not perturb the
      motor pattern for swimming. However, the cycle periods over which the locomotor
      rhythm generator could generate appropriate motor activity were lengthened by
      about 10% and the mean duration of swimming episodes was increased by
      approximately 40%. 6. We therefore propose that the Ca(2+)-dependent K+ current
      plays an important role in the self-termination of motor activity.

PMID- 8544122
TI  - Enhancing effect of calmodulin on Ca(2+)-induced Ca2+ release in the sarcoplasmic
      reticulum of rabbit skeletal muscle fibres.
AB  - 1. We analysed the effect of calmodulin on Ca(2+)-induced Ca2+ release (CICR) in
      the sarcoplasmic reticulum (SR) using chemically skinned fibres of rabbit psoas
      muscle. Ca2+ release was measured using fura-2 microfluorometry. 2. In saponin
      skinned fibres, calmodulin potentiated Ca2+ release at low Ca2+ concentrations (<
      3 microM), while it showed an inhibitory effect at high Ca2+ concentrations (3-30
      microM). 3. Co-application of ryanodine and calmodulin at 0.3 microM Ca2+, but
      not ryanodine alone, induced a decline in the Ca2+ uptake capacity of the SR, an
      effect expected from the open-lock of active CICR channels by ryanodine. Thus,
      potentiation of Ca2+ release by calmodulin at low Ca2+ concentrations can be
      regarded as a result of the activation of the ryanodine receptor. 4. Greater
      concentrations of calmodulin were required for potentiation of CICR at low Ca2+
      concentrations (1 microM) than for inhibition at high Ca2+ concentrations (10
      microM). 5. In beta-escin-permeabilized fibres in which intrinsic calmodulin was
      retained, the rates of CICR were similar to those measured in the presence of 1
      microM calmodulin in saponin-permeabilized fibres. 6. These results suggest that
      calmodulin plays an important role in the regulation of CICR channels in intact
      skeletal muscle fibres.

PMID- 8544123
TI  - Spatial profile of dendritic calcium transients evoked by action potentials in
      rat neocortical pyramidal neurones.
AB  - 1. Simultaneous measurements of intracellular free calcium concentration
      ([Ca2+]i) and intrasomatic and intradendritic membrane potential (Vm) were
      performed using fura-2 fluorimetry and whole-cell recording in neocortical layer
      V pyramidal neurones in rat brain slices. 2. Back-propagating action potentials
      (APs) evoked [Ca2+]i transients in the entire neurone including the soma, the
      axon initial segment, the apical dendrite up to the distal tuft branches, and the
      oblique and basal dendrites, indicating that following suprathreshold activation
      the entire dendritic tree is depolarized sufficiently to open voltage-dependent
      calcium channels (VDCCs). 3. The [Ca2+]i transient peak evoked by APs showed
      large differences between various compartments of the neurone. Following a single
      AP, up to 6-fold differences were measured, ranging from 43 +/- 14 nM in the soma
      to 267 +/- 109 nM in the basal dendrites. 4. Along the main apical dendrite, the
      [Ca2+]i transients evoked by single APs or trains of APs had the largest
      amplitude and the fastest decay in the proximal region; the [Ca2+]i transient
      peak and decay time constant following a single AP were 128 +/- 25 nM and 420 +/-
      150 ms, respectively, and following a train of five APs (at 10-12 Hz), 710 +/-
      214 nM and 390 +/- 150 ms, respectively. The [Ca2+]i transients gradually
      decreased in amplitude and broadened in more distal portions of the apical
      dendrite up to the main bifurcation. 5. In the apical tuft branches, the profile
      of the [Ca2+]i transients was dependent on AP frequency.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8544124
TI  - Local Ca2+ transients (Ca2+ sparks) originate at transverse tubules in rat heart
      cells.
AB  - 1. The origins of local [Ca2+]i transients (Ca2+ sparks) were studied using dual
      channel confocal laser scanning microscopy. Line scan images showing [Ca2+]i (as
      fluo-3 fluorescence) and the transverse tubule membranes (as Di-8 fluorescence)
      were obtained simultaneously in single rat cardiac ventricular cells. 2. Line
      scan images of Di-8 fluorescence showed peaks regularly spaced at intervals of
      1.83 +/- 0.30 microns (mean +/- S.D.). These peaks corresponded to the transverse
      tubules (T-tubules) in cross-section. 3. Line scan images of fluo-3 fluorescence
      showed local [Ca2+]i transients (LCTs or Ca2+ sparks) evoked by electrical
      stimulation. 4. Eighty-five per cent (85%) of all Ca2+ sparks evoked by
      electrical stimulation (n = 138, in 5 cells) occurred within 0.5 micron of a T
      tubule. Thirty per cent (30%) occurred within 1 pixel (0.20 micron) of a T
      tubule. 5. In some cells studied (3 out of 5), certain T-tubules had a higher
      probability of being sites of origin of Ca2+ sparks than others. 6. These results
      support local control theories of excitation-contraction coupling in which Ca2+
      release from the sarcoplasmic reticulum (SR) is triggered by a high local [Ca2+]i
      established between the L-type Ca2+ channels in the T-tubules and associated
      ryanodine receptor(s) in the junctional SR.

PMID- 8544125
TI  - Modulation of cardiac ryanodine receptors of swine and rabbit by a
      phosphorylation-dephosphorylation mechanism.
AB  - 1. The regulation of the cardiac Ca2+ release channel-ryanodine receptor (RyR) by
      exogenous acid phosphatase (AcPh) and purified Ca(2+)-calmodulin-dependent
      protein kinase II (CaMKII) was studied in swine and rabbit sarcoplasmic reticulum
      (SR) vesicles using [3H]ryanodine binding and planar bilayer reconstitution
      experiments. 2. Addition of AcPh (1-20 U ml-1) to a standard incubation medium
      increased [3H]ryanodine binding in a Ca(2+)-dependent manner. Stimulation was
      only readily apparent in media containing micromolar Ca2+ concentrations. 3.
      Scatchard analysis of [3H]ryanodine binding curves revealed that AcPh enhanced
      binding by increasing the affinity of the receptor for [3H]ryanodine without
      recruiting additional receptor sites (Kd, 9.8 +/- 0.85 and 3.9 +/- 0.65 nM; Bmax
      (the maximal receptor density), 1.45 +/- 0.14 and 1.47 +/- 0.12 pmol mg-1 for
      control and AcPh, respectively). The failure of AcPh to increase Bmax suggested
      that the number of receptors that were 'dormant' due to phosphorylation in the SR
      preparation was very small. 4. At the single channel level, AcPh increased the
      open probability (Po) of RyR channels by increasing the opening rate and inducing
      the appearance of a longer open state while having no effect on single channel
      conductance. Thus AcPh acted directly on RyR channels or a closely associated
      regulatory protein. 5. CaMKII decreased both [3H]ryanodine binding and Po of RyRs
      when added to medium supplemented with micromolar levels of Ca2+ and calmodulin
      (CaM). Addition of a synthetic peptide inhibitor of CaMKII, or replacement of ATP
      with the non-hydrolysable ATP analogue adenylyl[beta, gamma-methylene]
      diphosphate (AMP-PCP), prevented CaMKII inhibition of RyRs, suggesting that
      CaMKII acted specifically through a phosphorylation mechanism. 6. The inhibition
      of RyR channel activity by CaMKII was reversed by the addition of AcPh. Thus we
      showed that an in vitro phosphorylation-dephosphorylation mechanism effectively
      regulates RyRs. 7. The results suggest that intracellular signalling pathways
      that lead to activation of CaMKII may reduce efflux of Ca2+ from the SR by
      inhibition of RyR channel activity. The Ca2+ dependence of CaMKII inhibition
      suggests that the role of the phosphorylation mechanism is to modulate the RyR
      response to Ca2+.

PMID- 8544126
TI  - Rhythmical bursts induced by NMDA in guinea-pig cholinergic nucleus basalis
      neurones in vitro.
AB  - 1. Intracellular recordings were performed in neurones within the basal forebrain
      of guinea-pig brain slices. Following injection of biocytin (or biotinamide), a
      subset of recorded neurones which displayed distinct intrinsic membrane
      properties were confirmed as being cholinergic by immunohistochemical staining
      for choline acetyltransferase (ChAT). They were all located within the nucleus
      basalis magnocellularis. The response of the cholinergic cells to NMDA and to the
      agonists of the other glutamate receptors was tested by bath application of NMDA,
      t-ACPD, AMPA and kainate. 2. When depolarized from a hyperpolarized level,
      cholinergic basalis neurones display the intrinsic ability to discharge in
      rhythmic bursts that are generated by low-threshold Ca2+ spikes. In control
      solution, these rhythmic bursts were not sustained for more than 5-6 cycles.
      However, in the presence of NMDA when the membrane was held at a hyperpolarized
      level, low-threshold bursting activity was sustained for prolonged periods of
      time. This activity could be reversibly eliminated by D(-)-2-amino-5
      phosphonopentanoic acid (D-AP5), showing that it depended upon specific
      activation of NMDA receptors. 3. NMDA-induced, voltage-dependent, rhythmic
      depolarizations persisted in the presence of tetrodotoxin (TTX), indicating that
      they did not depend upon a TTX-sensitive Na+ current and were generated
      postsynaptically. The rhythmic depolarizations were, however, eliminated by the
      partial replacement of Na+ with choline, demonstrating that they did depend upon
      Na+, the major carrier of the NMDA current. 4. In the presence of TTX, the NMDA
      induced rhythmic depolarizations were also eliminated by removal of Ca2+ from or
      addition of Ni2+ to the bath, indicating that they also depended upon Ca2+, which
      is carried by both the NMDA current and the low-threshold Ca2+ current. The
      duration of the rhythmic depolarizations was increased in the presence of apamin,
      suggesting that the repolarization of the cells depended in part upon a Ca(2+)
      activated K+ (SK) conductance, but that other mechanisms were additionally
      involved in the repolarization phase of the bursting. 5. In both the absence and
      presence of TTX, the NMDA-induced rhythmic activity persisted when Mg2+ was
      removed from the medium, indicating that the sustained rhythmic depolarizations
      did not hinge upon the Mg2+ block of the NMDA channels during hyperpolarization.
      The voltage dependence of the NMDA-induced rhythmic depolarizations in the
      absence of Mg2+ appeared to be determined by the properties of the low-threshold
      Ca2+ spike in the cholinergic basalis neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8544127
TI  - NMDA receptor-mediated transmission of carotid body chemoreceptor input to
      expiratory bulbospinal neurones in dogs.
AB  - 1. This study tested the hypothesis that excitatory amino acid receptors mediate
      the excitatory response of expiratory bulbospinal neurones to carotid body
      chemoreceptor inputs. 2. Studies were carried out in thiopental sodium
      anaesthetized, paralysed, ventilated, vagotomized dogs. 3. Brisk, short-duration
      chemoreceptor activation was produced by bilateral bolus injections of CO2
      saturated saline (PCO2 > 700 mmHg) into the autoperfused carotid arteries. A
      pressurized-reservoir-solenoid valve system was used to deliver the CO2 bolus
      injections just prior to the onset of the neural expiratory phase, as determined
      from the phrenic neurogram, about once per minute. 4. Multibarrelled
      micropipettes were used to record neuronal unit activity and deliver
      neurotransmitter agents. Net responses of expiratory bulbospinal neurones to
      peripheral chemoreceptor activation were determined by subtracting the mean
      discharge frequencies (Fn) during three control expiratory cycles from the Fn
      during administration of a CO2 test bolus. The role of excitatory amino acid
      receptors in mediating this response was determined by comparing the baseline and
      bolus expiratory neuronal Fn before, during and after the pressure microejection
      of the NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP5) or the non-NMDA
      receptor antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl- benzo(f)quinoxaline
      (NBQX). Ejection rates of AP5 and NBQX were measured by monitoring the movement
      of the pipette meniscus. 5. AP5 reduced Fn during both the control and bolus
      cycles, as well as reducing the change in Fn between control and bolus cycles.
      NBQX had no effect on either baseline or bolus responses. 6. AP5 did not prevent
      excitation of expiratory bulbospinal neurones by AMPA. Coadministration of AMPA
      with AP5 prevented the AP5-mediated decrease in Fn but not the dose-dependent
      reduction in the CO2 bolus response. 7. Taken together, these data strongly
      suggest that the carotid chemoreceptor-mediated excitation of expiratory
      bulbospinal neurones is dependent on NMDA but not non-NMDA glutamate receptors.

PMID- 8544128
TI  - 5-HT2 receptor-controlled modulation of medullary respiratory neurones in the
      cat.
AB  - 1. The effects of the 5-HT2 receptor agonist alpha-methyl-5-HT were studied on
      the membrane of expiratory (E2) and post-inspiratory (PI) neurones, by
      intracellular recordings in the caudal medulla of anaesthetized cats. 2.
      Ionophoresis of alpha-Me-5-HT depolarized membrane potential and increased action
      potential frequency in a majority of neurones tested. Depolarization of neurones
      by alpha-Me-5-HT was accompanied by increased input resistance throughout all
      phases of the respiratory cycle. These effects were antagonized by ionophoresis
      of cinanserin, a receptor-blocking agent with high affinity for 5-HT2 receptors.
      3. E2 neurones were voltage clamped to measure membrane current changes induced
      by alpha-Me-5-HT ionophoresis. alpha-Me-5-HT induced a net inward current by
      reducing inspiratory-phase outward currents and increasing expiratory-phase
      inward currents. These changes were equivalent with steady membrane
      depolarization, decreased inspiratory phase membrane hyperpolarization and
      increased expiratory drive potential recorded from the same neurones in current
      clamp. 4. The effects of alpha-Me-5-HT are consistent with activation of 5-HT2
      receptors on E2 and PI neurones leading to blockade of synaptically activated and
      persistent conductances to potassium ions.

PMID- 8544129
TI  - Excitatory synaptic potentials dependent on metabotropic glutamate receptor
      activation in guinea-pig hippocampal pyramidal cells.
AB  - 1. Intracellular and extracellular recordings of CA1 and CA3 neurones were
      performed in guinea-pig hippocampal slices to examine synaptic activities
      dependent on metabotropic glutamate receptors (mGluRs). 2. Long burst activities
      were elicited by 4-aminopyridine in the presence of ionotropic glutamate receptor
      and GABAA receptor blockers (6-cyano-7-nitroquinoxaline-2,3-dione and 3-(RS-2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and picrotoxin). Long bursts
      were also elicited by alpha-dendrotoxin. 3. Long bursts consisted of a 5-25 s
      depolarization with overriding action potentials and occurred rhythmically at
      intervals ranging from 1 to 20 min. Long bursts were generated in a population of
      CA3 neurones and the synchronized output elicited long bursts in CA1 cells.
      Depolarizing potentials underlying long bursts in CA1 cells had a reversal
      potential of -14.8 +/- 5.1 mV. 4. Long burst-associated depolarizations in CA1
      neurones were suppressed by local application of L-(+)-2-amino-3
      phosphonopropionic acid (L-AP3) and of the phenylglycine derivatives (+)-alpha
      methyl-4-carboxyphenylglycine ((+)-MCPG), S-4-carboxyphenylglycine (S-4CPG) and S
      4-carboxy-3-hydroxyphenylglycine (S-4C3HPG). (-)-MCPG or atropine application did
      not affect the long burst-associated depolarization. 5. Bath perfusion of (+)
      MCPG (0.5 mM), S-4CPG (0.5 mM), S-4C3HPG (0.5 mM) or L-AP3 (1 mM) blocked the
      occurrence of long bursts. 6. The results suggest that the long burst-associated
      depolarizations are synaptic potentials dependent on mGluR activation. Activation
      of mGluRs may also be involved in the generation of synchronized long bursts in
      the CA3 region.

PMID- 8544130
TI  - GABAergic and glutamatergic effects on behaviour in fetal sheep.
AB  - 1. Studies were carried out in unanaesthetized fetal sheep at 125-135 days
      gestation to investigate neurotransmitters involved in behavioural state. 2.
      Catheters and electrodes were chronically placed to record tracheal and arterial
      pressure, electrocortical activity (ECoG), nuchal muscle activity and to instill
      drugs into the cerebrospinal fluid (CSF) of the fourth ventricle. 3.
      Administration of the N-methyl-D-aspartate receptor antagonists DL-2-amino-5
      phosphopentanoic acid (AP5) or (+)-5-methyl-10,11-dihydro-5H
      dibenzol[a,d]cyclohepten-5,10- iminemoleate (MK-801) increased the incidence of
      fetal behaviour characterized by low voltage ECoG, nuchal muscle activity and an
      increase in mean arterial blood pressure from 4.1 +/- 6 to 60.6 +/- 6.2% (mean +/
      S.E.M.) (AP5; P = 0.003) and from 7.6 +/- 3.6 to 50.8 +/- 7.0% (MK-801; P =
      0.004; values are expressed as the percentage of each 60 min period in which the
      state was present). 4. The incidence of fetal breathing during periods of low
      voltage (LV)-ECoG and nuchal muscle activity was 83.1 +/- 5.6%. The incidence of
      fetal breathing during LV-ECoG associated with nuchal muscle atonia was 63.1 +/-
      5.0% before AP5 or MK-801 and 64.4 +/- 9.8% after instillation of these drugs.
      The amplitude of fetal breaths increased from 4.0 +/- 0.3 mmHg in low voltage
      ECoG periods to 6.7 +/- 0.8 mmHg (P = 0.006) during periods of low voltage with
      nuchal muscle activity. There was no significant change in breath timing during
      these periods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544131
TI  - Interstitial space, electrical resistance and ion concentrations during hypotonia
      of rat hippocampal slices.
AB  - 1. The degree to which mammalian brain cells swell in hypotonic environments has
      not previously been determined. We exposed hippocampal tissue slices prepared
      from anaesthetized rats to artificial cerebrospinal fluid from which varying
      amounts of NaCl had been deleted. Interstitial volume (ISV) change was determined
      from the volume of dilution of the marker ions tetramethylammonium (TMA+) or
      tetraethylammonium (TEA+). Tissue electrical resistance was measured as the
      voltage generated by constant current pulses. 2. ISV decreased as a function of
      lowered extracellular osmolality (osmotic pressure, pi o), indicating cell
      swelling. After reaching a minimum, ISV recovered partially, suggesting
      regulatory volume decrease of cells. After restoring normal pi o the ISV
      expanded, indicating post-hypotonic cell shrinkage. The electrical resistance of
      the tissue (Ro) increased when pi o was lowered, due to the reduced ionic
      strength, as well as restricted ISV. 3. To control for low NaCl concentration,
      reduced NaCl was replaced by mannitol or fructose. In isosmotic, NaCl-deficient
      solution, ISV showed inconsistent change, and Ro corrected for ionic strength
      tended to decrease. 4. Extracellular K+ concentration decreased slightly in low
      pi o except when spreading depression caused it to increase. Extracellular Ca2+
      concentration decreased substantially, consistently and reversibly.
      Administration of isosmotic low-NaCl concentration solutions caused a similar
      decrease in extracellular Ca2+ concentrations. We propose that low Na+
      concentration in extracellular fluid impaired the extrusion of Ca2+. 5. In
      severely hypotonic solution, ISV was reduced to 25% of its control volume,
      corresponding to a mean cell volume increase of at least 11%, probably more. From
      plotting relative changes in ISV against osmolarity we concluded that, within the
      range tested, hypotonic cell swelling was not opposed by the close approach of
      plasma membranes of neighbouring cells.

PMID- 8544132
TI  - Comparison of energy output during ramp and staircase shortening in frog muscle
      fibres.
AB  - 1. We compared the rates of work and heat production during ramp shortening with
      those during staircase shortening (sequence of step releases of the same
      amplitude, separated by regular time intervals). Ramp or staircase shortening was
      applied to isolated muscle fibres (sarcomere length, 2.2 microns; temperature,
      approximately 1 degree C) at the plateau of an isometric tetanus. The total
      amount of shortening was no greater than 6% of the fibre length. 2. During ramp
      shortening the power output showed a maximum at about 0.8 fibre lengths per
      second (Lo s-1), which corresponds to 1/3 the maximum shortening velocity (Vo).
      For the same average shortening velocity during staircase shortening (step size,
      approximately 0.5% Lo) the power output was 40-60% lower. The rate of heat
      production for the same average shortening velocity was approximately 45% higher
      during staircase shortening than during ramp shortening. 3. The relation between
      rate of total energy output and shortening velocity was well described by a
      second order regression line in the range of velocities used (0.1-2.3 Lo s-1).
      For any shortening velocity the rate of total energy output (power plus heat
      rate) was not statistically different for staircase (step size, approximately
      0.5% Lo) and ramp shortening. 4. The mechanical efficiency (the ratio of the
      power over the total energy rate) during ramp shortening had a maximum value of
      0.36 at 1/5 Vo; during staircase shortening, for any given shortening velocity,
      the mechanical efficiency was reduced compared with ramp shortening: with a
      staircase step of about 0.5% Lo at 1/5 Vo the efficiency was approximately 0.2.
      5. The results indicate that a cross-bridge is able to convert different
      quantities of energy into work depending on the different shortening protocol
      used. The fraction of energy dissipated as heat is larger during staircase
      shortening than during ramp shortening.

PMID- 8544134
TI  - The pattern of excitatory inputs to the nucleus tractus solitarii evoked on
      stimulation in the hypothalamic defence area in the cat.
AB  - 1. In anaesthetized, paralysed and artificially ventilated cats, recordings have
      been made in the nucleus tractus solitarii (NTS) to assess further the role of
      this nucleus in mediating the cardiorespiratory responses that are elicited on
      stimulation within the hypothalamic defence area (HDA). 2. The responses of NTS
      neurones to stimulation in the hypothalamus were assessed, as were their patterns
      of evoked response to electrical stimulation of the sinus (SN), aortic (AN),
      superior laryngeal (SLN) and vagus (VN) nerves. 3. Stimulation in the HDA
      affected the activity of 110 NTS neurones (85 studied in intracellular and 25
      studied in extracellular recordings). The present study focused on those sixty
      eight neurones that were excited by such stimulation (51 intracellular recordings
      and 17 extracellular recordings). 4. Of the sixty-eight neurones that were
      excited by HDA stimulation, seven revealed no changes in membrane potential or
      evoked discharge (2 neurones) but the stimulus facilitated the excitatory effects
      of stimulating either (or both) the SN and SLN. An additional group of neurones
      showed powerful excitatory responses to HDA stimulation (15 studied with
      extracellular and 35 with intracellular recording). Evoked EPSPs had onset
      latencies in the range of 1-30 ms. Of those thirty-five neurones displaying
      EPSPs, twenty-six were shown to receive convergent inputs on nerve stimulation.
      In nine neurones the early EPSP in response to HDA stimulation was followed by an
      IPSP. 5. In a further group of neurones HDA stimulation elicited a long-lasting
      IPSP, but this was not analysed further because its features have been described
      in detail in earlier studies from this laboratory. 6. The patterns of response of
      several neurones excited by stimulation in the HDA are consistent with them
      forming a group of NTS interneurones that mediate the hypothalamically evoked
      cardiovascular responses, including modulation of reflex function, which is a
      major feature of cardiorespiratory control. This possibility is discussed in the
      light of the present physiological observations and descriptions of an intrinsic
      NTS group of GABA-containing neurones that have been suggested to fulfil such a
      role.

PMID- 8544133
TI  - The relationship between light-evoked synaptic excitation and spiking behaviour
      of salamander retinal ganglion cells.
AB  - 1. Light-evoked input-output characteristics of ganglion cells in dark-adapted
      tiger salamander retina were studied in the slice preparation using patch-clamp
      techniques. Excitatory postsynaptic currents (EPSCs), isolated by blocking
      inhibitory inputs and evoked by a range of light stimulus intensities, were
      recorded under whole-cell voltage clamp. Spike responses, evoked by the same
      light intensities, were recorded extracellularly from the same cells using the
      cell-attached patch-clamp technique. 2. When N-methyl-D-aspartate (NMDA) receptor
      mediated input was blocked by the competitive NMDA antagonist DL-2-amino-5
      phosphonoheptanoate (AP7), light-evoked EPSC amplitude and peak firing rate were
      reduced at all light intensities. In both cases, the data obtained in the
      presence of AP7 scaled linearly to control data, indicating that NMDA and non
      NMDA receptors are activated in the same proportions across the entire 2 log unit
      stimulus response range of these ganglion cells. 3. The relationship between
      light-evoked spike frequency and light-evoked EPSC amplitude was linear. The
      slope of the light-evoked synaptic current-spike frequency relationship was close
      to the slope of the injected current-spike frequency relationship, indicating
      that synaptic current and injected current drive spiking in a similar manner. The
      linearity of the synaptic current-spike frequency relationship was not
      compromised when NMDA input was blocked by AP7. 4. Light-evoked voltage
      responses, recorded under whole-cell current clamp, revealed that the average
      membrane potential during a spike response was depolarized only slightly with
      increased firing rate. Once the membrane potential surpassed spike threshold, it
      was maintained by the voltage-gated, spike-generating conductances at a
      depolarized plateau upon which action potentials were fired. The potential of
      this plateau varied only slightly with spike frequency. We conclude that the
      voltage control exerted by the spike-generating currents in ganglion cells
      prevents a substantial response-dependent decrease in the electrical driving
      force of the excitatory currents, obviating the need for the voltage-independent
      synaptic efficacy provided by the combination of NMDA and non-NMDA inputs.

PMID- 8544135
TI  - Hypothalamic modulation of laryngeal reflexes in the anaesthetized cat: role of
      the nucleus tractus solitarii.
AB  - 1. This investigation was initiated because activation of laryngeal afferents,
      either by electrical stimulation of the superior laryngeal nerve (SLN) or by
      natural stimulation of receptors in the laryngeal mucosa, results in a
      cardiorespiratory response comprising bradycardia, hypotension and apnoea
      (phrenic nerve activity was suppressed). This pattern of response is
      qualitatively equivalent to the response that is evoked on activation of the
      arterial baroreceptors. 2. Preliminary studies indicated that the effects of
      activating the SLN were suppressed during stimulation in the hypothalamic defence
      area (HDA) at points that also blocked the effects of baroreceptor stimulation.
      3. Recordings were taken from seventy-two neurones localized within the
      ipsilateral nucleus tractus solitarii (NTS) whose activity was modified by SLN
      stimulation. Sixty neurones responded with an EPSP on SLN stimulation; nine of
      these had an inspiratory firing pattern. Five neurones were seen to receive an
      IPSP on SLN stimulation. 4. Five respiratory SLN-activated neurones were
      unresponsive to stimulation of the other nerve inputs, whilst four received
      convergent EPSP inputs on sinus nerve (SN) stimulation. One cell of these four
      also received inputs from the aortic and the vagus nerves. Sixty-one non
      respiratory SLN-activated neurones also received convergent inputs from the sinus
      nerve. Of these, fifty displayed an EPSP, four an IPSP and seven an EPSP-IPSP.
      Fifteen neurones also received inputs from the aortic nerve and seventeen from
      the vagus. 5. From the population of neurones affected by SLN stimulation, twenty
      four of seventy were also influenced by HDA stimulation (3 were respiratory
      cells). Sixteen of these responses consisted of an EPSP (2 respiratory cells),
      five of an IPSP (1 respiratory cell) and three of an EPSP-IPSP. 6. In neurones
      receiving an IPSP on HDA stimulation, the SLN-evoked excitatory response was
      reduced throughout the period of HDA-evoked inhibition. These neurones were all
      shown to receive excitatory inputs from the arterial baroreceptors and laryngeal
      mechanoreceptors. 7. Additionally, in the thirty-seven neurones that were excited
      by SLN stimulation but received no direct synaptic input on HDA stimulation, a
      conditioning stimulus to the HDA evoked a block of SLN-evoked responses without
      an accompanying change in membrane potential. Several of these neurones were also
      affected by both baroreceptor and laryngeal mechanoreceptor stimulation. 8. These
      observations are discussed in the context of the role of the NTS in
      cardiorespiratory control. The potential importance of these interactions in
      respiratory distress are highlighted and the implications for the organization of
      central pathways for the control of autonomic and respiratory function are
      discussed.

PMID- 8544136
TI  - Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized
      cat: role of the nucleus tractus solitarii.
AB  - 1. There is evidence in the literature of a mutual facilitatory interaction
      between the arterial chemoreceptor reflex and the alerting stage of the defence
      reaction, particularly in relation to the patterning of cardiorespiratory
      activity. The present study has been designed to test the hypothesis that a
      portion of this interaction involves synaptic interactions within the nucleus
      tractus solitarii (NTS). 2. The study has involved an analysis of the effective
      interactions between the stimulation of the arterial chemoreceptors and the
      hypothalamic defence area (HDA) on the activity of NTS neurones recorded in
      anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen
      NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs
      on sinus nerve stimulation (SN) and their failure to show an excitatory response
      to baroreceptor stimulation. Thirteen of these neurones displayed pronounced
      excitatory responses to chemoreceptor stimulation. In sixteen of these neurones
      HDA stimulation elicited an EPSP; in four of these sixteen neurones this early
      EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA
      stimulation provoked no obvious synaptic response but facilitated the efficacy of
      both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive
      convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA,
      often displayed excitatory responses to stimulation of other peripheral inputs.
      Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in
      seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The
      organization of these synaptic interactions is discussed and these data are used
      to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA
      inputs within the NTS. Conclusions are drawn regarding the functional role of
      different classes of NTS neurone, based on the findings in this and the
      accompanying two papers.

PMID- 8544137
TI  - Heterogeneity of contraction-induced effects in neurons of the cat dorsal
      spinocerebellar tract.
AB  - 1. Clarke's column neurons of the dorsal spinocerebellar tract (DSCT) were
      recorded intracellularly in anaesthetized cats during weak sustained contractions
      of triceps surae (TS) produced by direct electrical stimulation of the muscle. 2.
      Of 145 DSCT neurons, 77 (53%) were contraction sensitive suggesting that
      information about weak contraction of a limited number of muscles is widely
      distributed among DSCT neurons. Four types of effects were observed in individual
      neurons during TS contractions. 3. In the first group of 11 DSCT neurons (14% of
      the contraction-sensitive cells), the effect was excitation persisting throughout
      the duration of contractions. These responses were ascribed to actions of
      afferents from contraction-activated tendon organs. 4. In a second group of 15
      neurons (20% of the contraction-sensitive cells), quickly declining excitatory
      potentials were recorded during sustained TS contractions. By analogy with
      previous observations of contraction-induced effects in motoneurons, the decline
      of excitation might be explained by contraction-induced presynaptic inhibition of
      group I afferents in Clarke's column. 5. Declining inhibitions, resembling those
      previously observed in homonymous and synergic motoneurons, were recorded in 49%
      of contraction-sensitive DSCT neurons. This appears in keeping with the fact that
      interneurons mediating Ib inhibition to motoneurons project axon collaterals to
      DSCT neurons. Presynaptic inhibition of Ib fibres might therefore cause parallel
      reductions of inhibitory potentials in motoneurons and in DSCT neurons. 6. In a
      final group of 13 neurons, mixed excitatory and inhibitory effects were observed
      during TS contractions. Such DSCT neurons might monitor the excitability of Ib
      interneurons by integration of information about input to and output from these
      neurons. 7. The non-uniform patterns of DSCT responses to TS contractions suggest
      complex processing of information on ankle extensor activity in cerebellum.
      Phasic signalling of contraction onset is observed in many DSCT neurons while
      others carry messages about duration and strength of contraction.

PMID- 8544138
TI  - Effects of vitamin E deficiency on autonomic neuroeffector mechanisms in the rat
      caecum, vas deferens and urinary bladder.
AB  - 1. Modified sucrose-gap, standard organ-bath techniques and transmitter release
      studies were used to examine neuromuscular transmission in the caecum, vas
      deferens and urinary bladder in normal rats and in rats maintained for 12 months
      on a diet free of vitamin E. 2. In the caecum circular muscle, non-adrenergic,
      non-cholinergic inhibitory junction potentials were absent from 48 and 15% of
      preparations from vitamin E-deficient and control animals, respectively.
      Cholinergic excitatory junction potentials were absent from 83 and 8% of vitamin
      E-deficient and control preparations, respectively. Responses to applied
      noradrenaline (0.1-30 microM), alpha,beta-methylene ATP (3-100 microM) and
      acetylcholine (0.1-30 microM) were attenuated or absent in vitamin E-deficient
      tissues. Responses to applied KCl were similar in both groups. Release of
      [3H]noradrenaline or endogenous acetylcholine could not be evoked from vitamin E
      deficient tissues. 3. In contrast, in isolated preparations of the vas deferens
      and urinary bladder, neuromuscular transmission by adrenergic, cholinergic and
      purinergic components were unaffected by long-term vitamin E deficiency. 4. In
      conclusion, vitamin E deficiency causes dysfunction of autonomic neuroeffector
      mechanisms in the smooth muscle of the rat caecum, at both a pre- and
      postjunctional level. The lesions in autonomic transmission mechanisms brought
      about by long-term vitamin E deficiency were found only in the caecum; no changes
      in sympathetic neuromuscular transmission were observed in the vas deferens, or
      in parasympathetic neuromuscular transmission in the urinary bladder.

PMID- 8544139
TI  - Time course of 'set'-related changes in muscle responses to stance perturbation
      in humans.
AB  - 1. In standing subjects, toe-down rotation of a supporting platform elicits a
      medium-latency response (MLR) in tibialis anterior (TA) muscle and a long-latency
      response (LLR) in soleus (Sol). Toe-up rotation induces a short-latency response
      (SLR) in Sol and a LLR in TA. When subjects steadily hold onto a stable frame,
      all responses are decreased, except Sol SLR. The aim of this investigation was to
      assess whether the response modulation is dependent on information from the hand
      touching the frame, or whether it anticipates the holding task. 2. The time
      course of the changes in response amplitude was studied in a time interval
      centred around the act of holding, performed in a reaction-time mode. Subjects
      kept their extended arm close to the frame in front of them and brought the hand
      in contact with the frame in response to a visual go-signal. The platform was
      moved at different intervals prior to or after the go-signal. Surface EMGs of
      Sol, TA and deltoid (Delt) were recorded. 3. TA MLR began to decrease when the
      platform was displaced at an interval of 140 ms after the go-signal, about 200 ms
      before subjects touched the frame and 120 ms before termination of Delt EMG. Four
      hundred milliseconds after the go-signal the response reached and maintained
      maximal inhibition, similar to that occurring under the stationary holding
      condition. The time course of inhibition of Sol LLR and TA LLR was similar to
      that of TA MLR, except that LLRs began to decrease at an earlier interval. Due to
      the different response latency from the onset of the perturbations, the beginning
      of inhibition of both MLRs and LLRs occurred almost simultaneously. 4. The
      changes in amplitude of leg muscle responses are not triggered by the go-signal,
      contact with the frame, or arm motion, suggesting that the modulation is related
      to the transition to a new, stabilized postural 'set'. The similar extent and
      parallel time course of MLR and LLR suppression, possibly transmitted through
      different pathways, points to the spinal cord as the site of action. The lack of
      depression of the monosynaptic SLR suggests an effect at premotoneuronal level.
      On the basis of selectivity, latency and time course of the effect, we favour the
      hypothesis that a monoaminergic pathway from the brainstem is involved.

PMID- 8544140
TI  - Roles of arachidonic acid, lipoxygenases and phosphatases in calcium-dependent
      modulation of M-current in bullfrog sympathetic neurons.
AB  - 1. M-current (IM) is regulated by intracellular free Ca2+ ([Ca2+]i). Suppression
      and overrecovery of IM induced by muscarine and luteinizing-hormone releasing
      hormone (LHRH) are also regulated by [Ca2+]i. The role of the arachidonic acid
      (AA) pathway in the Ca(2+)-dependent modulation of IM was investigated using
      whole-cell voltage clamp and intracellular perfusion in dissociated bullfrog
      sympathetic B neurons. 2. Quinacrine (10-20 microM) and 4-bromophenacyl bromide
      (4-BPB; 4-10 microM), the inhibitors of phospholipase A2, blocked the enhancement
      of IM evoked by raising [Ca2+]i. 3. AA (6-120 microM) increased IM by about 50%
      of the control current in a Ca(2+)-dependent manner. 4. Enhancements of IM by
      Ca2+ and AA were blocked by the lipoxygenase (LO) inhibitors nordihydroguaiaretic
      acid (NDGA; 1-5 microM) and 5,8,11-eicosatrynoic acid (ETI; 10 microM). The cyclo
      oxygenase inhibitor indomethacin (10 microM) had no effect. 5. Enhancement of IM
      by Ca2+ was abolished by the selective 12-LO inhibitors baicalein (1-2 microM)
      and 15(S)-hydroxy-5-cis-8-cis-11-cis-13-trans-eicosatetraenoic acid (15-HETE; 6.5
      microM). A 12-LO product, 2(S)-hydroxy-5-cis-8-cis-10-trans-14-cis-
      eicosatetraenoic acid (12-HETE; 13-20 microM), increased IM without Ca2+
      requirement. 6. Enhancement of IM by Ca2+ was not affected by the selective 5-LO
      inhibitors AA-861 (10 microM), 5,6-dehydroarachidonic acid (5,6-DAA, 10 microM)
      and L-651,896 (10 microM). The 5-LO metabolites leukotriene C4 (1.5-8 microM) and
      leukotriene B4 (1.5-5 microM) showed no obvious effect on IM. 7. NDGA alone
      inhibited IM with an IC50 of 0.73 microM at 120 nM Cai(2+). 8. NDGA did not
      affect suppression of IM by muscarine or LHRH; however, overrecovery of IM upon
      removing these agonists was totally eliminated by 1 microM NDGA. 9. Inhibitors of
      phosphatases, calyculin A (0.1 microM) and okadaic acid (1 microM), completely
      abolished overrecovery of IM. Calyculin A also blocked the Ca(2+)-induced IM
      enhancement. 10. It is suggested that Ca2+ enhances IM by stimulating the AA
      metabolic pathway. Dephosphorylation probably upregulates IM. Overrecovery of IM
      is probably a result of stimulation of the LO pathway and phosphatases by
      increased [Ca2+]i.

PMID- 8544141
TI  - The population paradox.

PMID- 8544142
TI  - A critique of Geoffrey Rose's 'population strategy' for preventive medicine.

PMID- 8544143
TI  - Social causes of low birth weight.
AB  - The manifest importance of reducing the incidence of low birth weight is most
      obvious for the first year of life: low birth weight is the single most important
      factor affecting infant morbidity and mortality. However, there is growing
      evidence that the adverse consequences of low birth weight continue throughout
      the life cycle. This review deals primarily with social causes of low birth
      weight.

PMID- 8544144
TI  - Appendicitis: an African perspective.

PMID- 8544145
TI  - The need for evidence-based medicine.
AB  - As physicians, whether serving individual patients or populations, we always have
      sought to base our decisions and actions on the best possible evidence. The
      ascendancy of the randomized trial heralded a fundamental shift in the way that
      we establish the clinical bases for diagnosis, prognosis, and therapeutics. The
      ability to track down, critically appraise (for its validity and usefulness), and
      incorporate this rapidly growing body of evidence into one's clinical practice
      has been named 'evidence-based medicine' (EBM).

PMID- 8544146
TI  - The causes of ordinary colorectal adenomas: the key to the control of colorectal
      cancer?

PMID- 8544147
TI  - Age-related geriatric medicine: relevance of special skills of geriatric medicine
      to elderly people admitted to hospital as medical emergencies.
AB  - This study was carried out to find out how many patients aged 75 and over
      admitted to hospital as medical emergencies had features appropriate to care by
      physicians in geriatric medicine and to examine the extent of use of specialist
      facilities by these patients. The purpose was to examine criticisms of age
      related admission policies which have focused on misplacement of patients with
      single diagnoses and lack of access to specialist care. An analysis was made of
      admission, process and discharge characteristics relevant to the special skills
      of geriatric medicine, multiple pathology and use of specialist services by 554
      patients aged 75 and over. These were collected prospectively, consecutively
      admitted as medical emergencies via the accident and emergency department of a
      large district general hospital with an age-related (75 and over) medical
      admissions policy. 84 patients (15%) had single pathology and no characteristics
      suggesting the need for specialist geriatric care. 177 (32%) had single pathology
      and one or more specialized characteristics. 66 (12%) had multiple pathology
      alone. 227 (41%) had multiple pathology and specialized characteristics. There
      were 142 specialist referrals in 121 patients (22% of the whole sample). We
      concluded that the special skills of general physicians specializing in the
      medical and associated community problems of elderly people are highly relevant
      to patients aged 75 and over presenting as medical emergencies. There was no
      evidence of lack of involvement of specialists in their care.

PMID- 8544148
TI  - Risk factors for HIV infection overlooked in routine antenatal care.
AB  - We have ascertained the extent to which risk factors for HIV infection may escape
      detection by standard history-taking procedures in an antenatal clinic. This
      study was based on 1264 women from a multi-ethnic population in an inner London
      health district (City and Hackney). All had agreed to undergo attributable HIV
      testing and a detailed personal interview. Thirty-nine per cent (494 of 1264
      women) reported risk factors contributed personally or by a partner. Most of
      these risk factors had not been earlier disclosed by routine history taking. In
      most cases the risk was residence and risk activity in a World Health
      Organization (WHO) Pattern 2 country. [HIV spread WHO categories: Pattern 1-
      principally homosexual/bisexual males and i.v. drug use (areas = North America,
      Western Europe, Australasia, parts of South America) with male to female ratio
      10/1; Pattern 2--Heterosexual (areas = Sub Saharan Africa, Caribbean and part
      South America) with male to female 1/1.] Thirty-one subjects (2.4%) were aware
      that their partners had participated in bisexual activity. Only six subjects
      perceived themselves at risk through their own or partner's drug injecting
      activity. The frequency of risk factors was substantially greater than that
      ascertained by the routine history. The findings highlight the potential risk of
      heterosexual spread resulting from travel to or residence in high prevalence
      territories. The contribution by male partners is significant and is particularly
      difficult to detect during a routine interview. These data support the
      recommendation that voluntary HIV serum testing should be universal rather than a
      selective offer based on risk factors determined at a routine history.

PMID- 8544149
TI  - Depressive disorder due to craniopharyngioma.
AB  - Secondary causes of depression are legion, and must always be considered in
      patients presenting with features atypical of primary idiopathic depressive
      disorder. The case described is that of a middle-aged woman presenting initially
      with a major depressive disorder who was subsequently found to have a
      craniopharyngioma, leading to a revised diagnosis of mood disorder due to the
      tumour. Some features of the presentation might have led to earlier diagnosis had
      their localizing significance been recognized. Diencephalic lesions should always
      be considered in patients presenting with the hypersomnic-hyperphagic variant of
      depressive disorder.

PMID- 8544150
TI  - The Hughlings Jackson Lecture: autoimmunity and the nervous system.

PMID- 8544151
TI  - An analysis of the costs of alternative treatments for benign prostatic
      hypertrophy.

PMID- 8544152
TI  - Chemotherapy of human nematodes: learning from the problems in sheep.

PMID- 8544153
TI  - Understanding American health-care and health-care reform.

PMID- 8544154
TI  - Iso-osmotic bowel preparation improves the accuracy of iliac artery colour flow
      duplex examination.
AB  - Colour flow duplex ultrasonography is currently the non-invasive method of choice
      for investigating the iliac arteries. However it is only 84-92% sensitive in the
      best hands when compared with biplanar angiography. Bowel gas and faeces
      overlying the iliac arteries obscure the vessels and prevent a good ultrasound
      image. We have previously shown that preparation of the bowel with an iso-osmotic
      bowel preparation (Klean Prep) improves the clarity of duplex image of the iliac
      arteries. This is caused by a volume effect which flushes out gas and faeces,
      leaving a fluid-filled bowel transparent to ultrasound. The aim of this study was
      to investigate whether this enhanced image increased the diagnostic accuracy of
      duplex examination. We performed iliac duplex examinations on 56 patients with
      clinically suspected iliac artery disease, initially with the normal preparation
      of starving the patients for 12 h and subsequently after preparation by Klean
      Prep. The results from each investigation were compared with the gold standard of
      biplanar intra-arterial digital substraction angiography. The use of iso-osmotic
      bowel preparation (Klean Prep) significantly improved the accuracy of iliac
      duplex ultrasonography over preparation by 12 h starvation, when compared with
      biplanar angiography.

PMID- 8544155
TI  - Inspecting the colon from inside and out to solve pyrexia of unknown origin.
AB  - A man with longstanding intermittent symptoms of abdominal pain, diarrhoea and
      pyrexia of unknown origin was diagnosed with the novel technique of laparoscopic
      assisted colonoscopy. At subsequent laparotomy, a longstanding perforation of
      sigmoid diverticular disease was resected, with resolution of his symptoms.

PMID- 8544156
TI  - Breast cancer and condoms.

PMID- 8544157
TI  - EMLA and venepuncture.

PMID- 8544158
TI  - The effect of molybdenum and sulphur on anthelmintic resistant Haemonchus
      contortus in sheep.

PMID- 8544159
TI  - Acute selenium toxicosis as a cause of paralysis in pigs.

PMID- 8544160
TI  - Success with intravaginal insemination of frozen-thawed dog semen--a
      retrospective study.
AB  - This retrospective study reports on the fertility of bitches (n = 40) that were
      inseminated into the fornix vaginae with frozen-thawed sperm from 9 sperm donors.
      In most bitches, the inseminations were repeated daily although, in 5 bitches, 1
      2 d were skipped between some inseminations. All semen had been frozen by the
      same method and all prostatic fluid had been frozen at -18 degrees C prior to
      use. Sixteen Beagle bitches (Group 1) were inseminated with frozen-thawed semen
      to which 3-5 ml prostatic fluid had been added post-thaw. Ten German Shepherds
      and 4 other bitches of similar size (Group 2) were inseminated after adding 6-10
      ml prostatic fluid to the frozen-thawed semen. Ten different German Shepherd
      bitches (Group 3) were inseminated without using prostatic fluid. The volumes of
      individual insemination doses were 3.5-6 ml, 7-12 ml and 1-3 ml for Groups 1, 2
      and 3 respectively. The number of progressively motile sperm per insemination
      varied from 9 x 10(6) to 300 x 10(6). Sixteen of 16, 13 of 14 and 6 of 10 bitches
      conceived in Groups 1, 2 and 3 respectively. Mean litter sizes were 4; 5.6 and 4
      in Groups 1, 2 and 3 respectively. The pregnancy rate of Groups 1 and 2 combined
      was higher than that of Group 3 (P < 0.01). The mean number of foetuses per bitch
      bred was 5.2 (SD 3.2) for Group 2, which was higher than the 2.4 (SD 2.8) of
      Group 3 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544161
TI  - Short-term effects of dietary cation:anion balance on bone mineral homeostasis in
      the bovine.
AB  - Fifteen Friesian oxen between 12 and 18 months of age with a mean body mass of
      240.7 kg, were randomly assigned to diets containing 0.25% phosphorus (P) or
      less, to evaluate the acute effects of a dietary cation:anion balance (DCAB) of
      either -11.1, +16.5 or +25.6 mmol 100 g-1 diet dry matter calculated as (Na+K) -
      (Cl+S), on blood, bone and faecal P, calcium (Ca) and magnesium (Mg) for a period
      of 9 weeks. Bone and faecal P concentrations were significantly (P < 0.05) higher
      in the anionic treatment group compared with the cationic and control treatment
      groups. The same was true for blood P, but significant (P < 0.05) only when
      compared with the cationic treatment group. Bone Ca was lower (NS) and blood Ca
      was significantly (P < 0.05) higher in the cationic compared to the anionic and
      control treatment groups, but faecal Ca was significantly (P < 0.05) higher in
      the anionic compared to the cationic, and control treatments groups. There was
      little difference in blood and bone Mg content among treatment groups, but faecal
      Mg was significantly (P < 0.05) higher in the anionic treatment group compared to
      the other 2 treatment groups. Whether this was due to the anionic nature of the
      diet or dietary concentration of Mg is unclear. Results from this research
      indicate a P sparing effect in which a low DCAB may improve the availability of P
      in animals where dietary P is limiting. In critical evaluations, weekly sampling
      of rib bone should be used to give a more accurate assessment of acute changes in
      bone mineral.

PMID- 8544162
TI  - Immune responses to South African Babesia canis and the development of a
      preliminary vaccine.
AB  - The immune responses of 2 Beagles to live parasites of an isolated B. canis
      strain were tested. The dogs were infected with live parasites and were carefully
      treated to allow the parasites to remain in the dogs' bodies for long enough to
      evoke an immune response. Once recovered from the initial infections, both dogs
      received 2 separate homologous challenges with live parasites. During the second
      challenge, neither dog showed clinical signs of disease. An experimental vaccine
      was developed against the isolated B. canis strain by growing parasites in a
      micro-aerophilous stationary phase cell culture system to provide (a) antigen
      containing supernatant material and (b) pellet material containing dead
      parasites. Two dogs each were inoculated with the different formulations of the
      vaccine on 2 separate occasions. Three weeks after the second inoculation, all 4
      dogs were challenged with live parasites. Three of the 4 dogs recovered from the
      challenge without any anti-babesial treatment.

PMID- 8544163
TI  - Anthelmintic sales in the highveld region of Eastern Transvaal.
AB  - Throughout a survey from 1991 to 1993 in the Highveld region of Eastern
      Transvaal, levamisole sales dominated in the sheep anthelmintic market. The
      macrocyclic lactone sales dominated in the cattle anthelmintic market, but were
      superseded by those of levamisole in 1993. The salicylanilides enjoyed the second
      highest demand in the sheep anthelmintic market. Anthelmintics were purchased
      throughout the year, but sales peaked in summer and autumn. When it rained in
      winter, sales increased during winter and peaked in spring. Eastern Transvaal Co
      operative (OTK) sold 2,64 therapeutic doses per sheep during the driest year and
      3,54 per sheep during the wettest year in the Highveld region. Only 24-29% of the
      cattle in the region could be treated with the anthelmintics sold by OTK for
      cattle. Total sales are estimated at double these figures.

PMID- 8544164
TI  - Melioidosis in a goat.
AB  - Melioidosis was diagnosed in an adult Boer goat ewe. The owner initially noticed
      swelling of one half of the udder. Several firm nodules developed in the affected
      part of the udder 2 weeks later. At necropsy, abscesses containing a creamy to
      yellowish-green exudate were found in the mammary gland and one of the kidneys.
      Pure cultures of Pseudomonas pseudomallei were isolated from the abscesses in the
      udder and inoculation of male guinea-pigs with the causative bacterium, produced
      a Shwartzman reaction in the testis and serositis as well as necrotic lesions, in
      parenchymatous organs. The isolate showed sensitivity to amoxycillin-clavulanate,
      but resistance to a number of other antimicrobials. This appears to be the first
      case of melioidosis in a domestic animal in South Africa.

PMID- 8544165
TI  - Fertility of two bulls with poor sperm morphology.
AB  - The aim of this study was to determine the degree of subfertility of 2 Friesland
      bulls (Bulls 1 and 2) with poor sperm morphology. An Ayrshire (Bull 3) with good
      sperm morphology served as control. Bull 1 had a mean of 48% morphologically
      normal sperm, 36% sperm-head defects and 18% flagellar defects. Bull 2 had a mean
      of 28% normal sperm, 28% flagellar defects and 33% proximal cytoplasmic droplets.
      Bull 3 had a mean of 83% normal sperm. Each bull was exposed to 19 cyclic
      heifers. Heifers of Breeding Groups 1, 2 and 3 did not differ with respect to
      body mass, age and breed. Pregnancy was diagnosed by means of B-mode
      ultrasonography 25-50 d after service. Bulls 1, 2 and 3 served 13, 17 and 16
      heifers, respectively, during one oestrous period each. Of these heifers 6 (46%),
      2 (12%) and 12 (75%) respectively, conceived.

PMID- 8544166
TI  - Two outbreaks of type C and type D botulism in sheep and goats in south Africa.
AB  - Two outbreaks of botulism in sheep and goats are described; in one, 329 out of
      900 sheep in a feedlot died within 9 d of the onset of the disease and in the
      other, 100 sheep and goats out of 330 succumbed over a period of about 3 weeks.
      Animals were found dead or died suddenly, without exhibiting clinical signs.
      Others stood with lowered heads and showed drooling of saliva or a stiff gait.
      Paresis and/or paralysis were frequent signs in the terminal stages of the
      disease. Gross lesions such as the accumulation of fluids in body cavities,
      pulmonary oedema, foam in the trachea, epicardial haemorrhages and congestion of
      the mucosa of the small intestine, suggestive of heart failure, were present in
      animals from both outbreaks. Botulism was confirmed via the mouse toxicity test,
      by the demonstration of Type C and Type D toxins in the feed and intestinal
      contents of sheep from the first outbreak and Type D toxin in intestinal contents
      of sheep from the second. The clinical signs and macropathology in the outbreaks
      of botulism in sheep and goats in South Africa may resemble "krimpsiekte" and
      cardiac glycoside and ionophore poisoning, as well as other conditions causing
      heart failure.

PMID- 8544167
TI  - Chronic fluorosis in cattle due to the ingestion of a commercial lick.
AB  - A year after introduction of a lick known to contain a commercial phosphorous
      source intended for agronomical purposes, approximately 2% adult cattle, from a
      herd numbering 120 animals, were observed to show signs of lameness. Four years
      later, this prevalence had increased to 5%, but teeth abnormalities were evident
      in 70-80% of animals. The average fluoride concentration of 5 coccygeal bone
      samples from 4-year-old animals was 6.94 x 10(3) mg kg-1. A lick sample had a
      fluoride concentration of 1.4 x 10(3) mg kg-1. A water and pasture sample
      contained 0.03 ppm and 0.3 ppm fluoride respectively. These values suggested that
      the lick was responsible for the clinical signs of chronic fluororis in the herd.

PMID- 8544168
TI  - Radiographic artifacts.
AB  - Radiographic artifacts commonly occur, particularly with hand processing. The
      artifacts may originate between the X-ray tube and the cassette as extraneous
      material on the patient or contamination of positioning aids, or result from
      debris within the cassette, or damage to, or staining of the screens. These
      artifacts are white to grey, may have a constant or different position on follow
      up radiographs, and their size and shape are reflective of the inciting cause. A
      number of artifacts may occur in the darkroom during handling, developing, fixing
      and drying of the film. White to shiny artifacts are caused by the contamination
      of films with fixer, inability of developer to reach parts of the film or loss of
      emulsion from the developed film. Black artifacts result from improper handling
      or storage of films, resulting in exposure to light, or from pressure marks or
      static electricity discharges. Dropped levels of hand-processing chemicals may
      result in a variety of tide-marks on films. Most radiographic artifacts can be
      prevented by proper storage and handling of films and by optimal darkroom
      technique.

PMID- 8544169
TI  - Supportive treatment of canine babesiosis.
AB  - Specific treatment of canine babesiosis consists of antibabesial drugs and, in
      severely anaemic animals, blood transfusion. Supportive therapy is also required,
      particularly in animals with complicated disease. Strategies for treatment of
      uncomplicated and complicated babesiosis are discussed. Definitive
      recommendations cannot be provided on the basis of available information, but
      suggestions are made, based on accepted therapeutic principles,
      pathophysiological mechanisms, therapy used in human malaria, and clinical
      experience. The problems of fluid therapy in complicated babesiosis, particularly
      in animals with oliguria, cerebral babesiosis and pulmonary oedema, are
      presented, with consideration given to the use of hypertonic fluids. The benefits
      of bicarbonate and alternative alkalinisers in life-threatening lactic acidaemia,
      a relatively common occurrence in complicated babesiosis, are debated, as are the
      benefits of oxygen therapy in anaemic hypoxia. Drug therapy and management of
      specific babesial complications are discussed. The rationale for supportive drugs
      commonly used in uncomplicated babesiosis, including lipotropic agents,
      haematinics and glucocorticoids, is examined. This review is designed to propose
      therapeutic guidelines and to stimulate interest in problematic aspects of
      supportive therapy for canine babesiosis.

PMID- 8544170
TI  - Computational methods to predict binding free energy in ligand-receptor
      complexes.

PMID- 8544171
TI  - Structure-based design of sulfonamide-substituted non-peptidic HIV protease
      inhibitors.

PMID- 8544172
TI  - Introduction of a conformational switching element on a pyrrolidine ring.
      Synthesis and evaluation of (R*,R*)-(+/-)-methyl 3-acetyl-4-[3- (cyclopentyloxy)
      4-methoxyphenyl]-3-methyl-1-pyrrolidinecarboxylate, a potent and selective
      inhibitor of cAMP-specific phosphodiesterase.

PMID- 8544173
TI  - Rational design and synthesis of small molecule, non-oligosaccharide selectin
      inhibitors: (alpha-D-mannopyranosyloxy)biphenyl-substituted carboxylic acids.
AB  - The calcium dependent E-selectin/sialyl Lewisx (sLex) interaction plays a key
      role in inflammation where it mediates the rolling of leukocytes prior to firm
      adhesion and extravasation from the vasculature. A model of E-selectin/sLex
      binding, along with previously reported structure-activity relationships of sLex
      related oligosaccharide, was used in the rational design of non-oligosaccharide
      inhibitors of this pivotal interaction. A palladium-mediated biaryl-coupling
      (Suzuki) reaction was used as the key step to prepare a number of substituted
      biphenyls which were assayed for their ability to inhibit the binding of E-, P-,
      and L-selectin-IgG fusion proteins to sLex expressed on the surface of HL60
      cells. Some of the compounds developed had greater in vitro potency than the
      parent sLex tetrasaccharide and are currently being evaluated in in vivo models
      of inflammation to select a candidate for clinical development.

PMID- 8544174
TI  - Discovery of an orally bioavailable NK1 receptor antagonist, (2S,3S)-(2-methoxy-5
      tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine (GR203040), with potent
      antiemetic activity.
AB  - The antiemetic, pharmacokinetic, and metabolic profile of CP-99,994, a potent NK1
      receptor antagonist, has been carefully evaluated. As a result we began a
      medicinal chemistry program which initially identified a 3-furanyl analogue (6)
      with improved antiemetic potency and a methyl sulfone (5) with enhanced metabolic
      stability and oral bioavailability. The improved pharmacokinetic profile of
      methyl sulfone (5) was associated with its low lipophilicity, and a therefore a
      number of heterocyclic analogues with reduced log D were synthesized. Out of this
      program emerged 19 (GR203040), a tetrazolyl-substituted analogue. Tetrazole 19
      inhibits radiation-induced emesis in the ferret with high potency when
      administered both subcutaneously and orally, has a long duration of action, and
      has high oral bioavailability in the dog. Tetrazole 19 is currently undergoing
      evaluation as a novel approach for the control of emesis associated with, for
      example, cancer chemotherapy.

PMID- 8544175
TI  - Synthesis, structure-affinity relationships, and biological activities of ligands
      binding to retinoic acid receptor subtypes.
AB  - The retinoic acid receptors (RARs) transduce retinoid dependant gene regulation,
      and many biological effects of retinoids are mediated through binding and
      activation of three closely related receptor subtypes (RAR alpha, RAR beta, and
      RAR gamma). In order to investigate the role of receptor subtypes, we have
      carried out a chemical synthesis program to seek selective retinoids for these
      receptors. We measured receptor binding affinity using recombinant RAR alpha, 
      beta, and -gamma proteins and assessed cellular differentiating activity in F9
      murine teratocarcinoma cells (F9 cells). This research has identified the 4
      substituted-3-(1-adamantyl)phenyl moiety as a new pharmacophore which can replace
      the beta-cyclogeranylidene ring of the naturally occurring all-trans-retinoic
      acid. Two chemical series derived from the general structures 6-(3
      tertioalkylphenyl)-2-naphthoic acid (series I) and 4-[(E)-2-(3
      tertioalkylphenyl)propenyl]benzoic acid (series II) were developed. In
      particular, we have obtained the RAR gamma selective derivatives 6-[3-(1
      adamantyl)-4-hydroxyphenyl]-2-naphthoic acid (7) [Ki(RAR alpha) = 6500 nM, Ki(RAR
      beta) = 2480 nM, Ki(RAR gamma) = 77 nM] and 4-[(E)-2-[3-(1-adamantyl)-4
      hydroxyphenyl]propenyl]benzoic acid (19) [Ki(RAR alpha) = 1,144 nM, Ki(RAR beta)
      = 1245 nM, Ki(RAR gamma) = 53 nM]. In series I, the presence of a phenol group,
      irrespective of the nature of tertioalkyl group, imparted at least partial RAR
      gamma selectivity, whereas in series II, the presence of both adamantyl and
      phenol groups is needed to confer RAR gamma selectivity. The RAR gamma selective
      ligands induce differentiation in F9 cells (7, AC50 = 33 nM; 19, AC50 = 66 nM).
      From series I, a mixed RAR beta-gamma agonist with potent cellular
      differentiating activity was selected for development as a topical antiacne
      agent, 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid (5, CD 271) [Ki(RAR
      alpha) = 1100 nM, Ki-(RAR beta) = 34 nM, Ki(RAR gamma) = 130 nM, AC50(F9) = 37
      nM]. Finally, from series II, we have obtained a weak antagonist in the F9
      cellular differentiation assay, 4-[(E)-2-(3-tert-butyl-4
      hydroxyphenyl)propenyl]benzoic acid (15, IC50 = 700 nM).

PMID- 8544176
TI  - Identification, characterization and pharmacological profile of three metabolites
      of (R)-(+)-1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenylcyclohexen-1-
      yl)methyl]pyridine (CI-1007), a dopamine autoreceptor agonist and potential
      antipsychotic agent.
AB  - Liquid chromatographic-mass spectrometric (LC-MS) analysis of plasma taken from
      cynomolgus monkeys dosed orally with (R)-(+)-1,2,3,6-tetrahydro-4-phenyl-1-[(3
      phenylcyclohexen-1- yl)methyl]pyridine (1), a dopamine (DA) autoreceptor agonist
      and potential antipsychotic agent, revealed several metabolites. The molecular
      masses of three major metabolites suggested that they were mono- and
      dihydroxylated derivatives of 1. We synthesized compounds 2 and 3, the two
      possible mono-p-hydroxyphenyl derivatives of 1, along with the bis-p
      hydroxyphenyl derivative 4. These compounds coeluted by HPLC with the three
      hydroxylated metabolites of 1. Compounds 2-4 all had high affinities for DA D2
      and D3 receptors and moderate affinities for D4 receptors. Like 1, compound 2
      decreased DA synthesis and neuronal firing in rat brain, indicative of DA
      autoreceptor activation. Compound 2 inhibited exploratory locomotor activity in
      rodents and was active in the Sidman avoidance test in squirrel monkeys,
      predictive of antipsychotic activity in humans. Compounds 3 and 4 showed weak
      activity in all these tests. After squirrel monkeys were dosed with 1 orally at
      the ED100 dose of the Sidman avoidance test, the plasma concentration of 2 was
      below the limit of quantitation. Therefore, these metabolites are unlikely to
      contribute greatly to the potent activity seen with 1 in the Sidman avoidance
      test.

PMID- 8544177
TI  - Chemistry and antimicrobial activity of caryoynencins analogs.
AB  - Caryoynencins (1) are antibiotics isolated from liquid cultures of a plant
      pathogen, Pseudomonas caryophylli, and are unstable C18 carboxylic acids with a
      conjugated dienetetrayne structure. Enyne analogs of caryoynencins were
      synthesized from monosilylated 1,3-butadiyne 2 (n = 2), 1,3,5-hexatriyne 2 (n =
      3), and 1,3,5,7-octatetrayne 2 (n = 4) by alkynyl metal addition to 2,4
      hexadienal (3) followed by allylic rearrangement and deprotection. Tetraynol 5 (n
      = 4) thus obtained was resolved by enzyme reactions. The conjugated dienetetrayne
      compounds are mixtures of 3E,5E- and 3E,5Z-isomers, which equilibrate by room
      light. 13C-NMR chemical shifts of polyynes obey simple rules, which can be used
      for signal assignments. Antimicrobial activities of conjugated enynes and related
      compounds were examined. The tetrayne analog 6 (n = 4) possesses potent
      antibacterial and antifungal activities, while triyne and diyne analogs 6 (n = 3
      and 2) are less active. Chirality does not affect the activities. An isomeric
      enyne compound, 2,4-tetradecadiene-7,9,11,13-tetrayn-6-ol (8), showed potent
      activity against Tricophyton.

PMID- 8544178
TI  - New alpha-thiol dipeptide dual inhibitors of angiotensin-I converting enzyme and
      neutral endopeptidase EC 3.4.24.11.
AB  - Dual inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP, EC
      3.4.24.11) and angiotensin-I converting enzyme, have been the focus of much
      clinical interest for the treatment of hypertension and congestive heart failure.
      A novel series of alpha-thio dipeptides containing central cyclic non-natural
      amino acids were prepared and were evaluated for their ability to inhibit these
      two metallopeptidases in vitro and in vivo. Most of these compounds were found to
      be excellent dual inhibitors of ACE and NEP in vitro and several were also found
      to inhibit angiotensin-I (AI) pressor response in conscious rats when given by
      intravenous administration. Compound 6n, one of our most potent dual inhibitors
      in vitro, was found to be more efficacious than captopril in the AI pressor
      experiment when administered orally to conscious rats. This compound was also
      found to inhibit plasma NEP activity following oral administration to conscious
      rats and was more efficacious than acetorphan. The structure-activity
      relationships and biological activity of these dual inhibitors will be discussed.

PMID- 8544180
TI  - Structure-activity relationships of the antimalarial agent artemisinin. 2. Effect
      of heteroatom substitution at O-11: synthesis and bioassay of N-alkyl-11-aza-9
      desmethylartemisinins.
AB  - A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemisinins 17
      29, were synthesized via ozonolysis and acid-catalyzed cyclization of precursor
      amides 5-16. These amides were prepared through condensation of an activated
      ester of the known intermediate acid 2 with the corresponding primary amine. The
      analogs were tested in vitro against W-2 and D-6 strains of Plasmodium falciparum
      and found in some cases to be more active than artemisinin. A comparison of the
      in vitro testing methods of Milhous and Makler was conducted and gave similar
      relative antimalarial activities for these artemisinin analogs. Log P values were
      determined for most of the compounds, but no apparent correlation between log P
      and in vitro activity was found.

PMID- 8544179
TI  - In vitro antimalarial activity of chalcones and their derivatives.
AB  - A series of chalcones and their derivatives have been synthesized and identified
      as novel potential antimalarials using both molecular modeling and in vitro
      testing against the intact parasite. A large number of chalcones and their
      derivatives were prepared using one-step Claisen-Schmidt condensations of
      aldehydes with methyl ketones. These condensates were screened in vitro against
      both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium
      falciparum and shown to be active at concentrations in the nanomolar range. The
      most active chalcone derivative, 1-(2,5-dichlorophenyl)-3-(4-quinolinyl)-2-propen
      1-one (7), had an IC50 value of 200 nM against both a chloroquine-resistant
      strain (W2) and a chloroquine-sensitive strain (D6). The resistance indexes for
      all compounds were substantially lower than for chloroquine, suggesting that this
      series will be active against chloroquine-resistant malaria. Structure-activity
      relationships (SAR) of the chalcones in the context of a homology-based model
      structure of the malaria trophozoite cysteine protease, the most likely target
      enzyme, are presented.

PMID- 8544181
TI  - Syntheses and antimalarial activities of N-substituted 11-azaartemisinins.
AB  - A two-step reaction sequence between artemisinin and methanolic ammonia followed
      by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield.
      Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in
      the reaction sequence yields N-substituted 11-azaartemisinins in similar or
      greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica
      gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin,
      are formed in 45% and 15% yields, respectively. In vitro and in vivo test data
      for a number of novel N-substituted 11-azaartemisinins, against drug-resistant
      strains of Plasmodium falciparum, show they possess antimalarial activities equal
      to or greater than that of artemisinin. The most active derivative, N-(2'
      acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4
      times more active in vivo than artemisinin.

PMID- 8544182
TI  - Optimization of alkylating agent prodrugs derived from phenol and aniline
      mustards: a new clinical candidate prodrug (ZD2767) for antibody-directed enzyme
      prodrug therapy (ADEPT).
AB  - Sixteen novel potential prodrugs derived from phenol or aniline mustards and
      their 16 corresponding drugs with ring substitution and/or different alkylating
      functionalities were designed. The [[[4-]bis(2-bromoethyl)-(1a), [[[4-[bis(2
      iodoethyl)-(1b), and [[[4-[(2-chloroethyl)-[2-(mesyloxy)ethyl]amino]phenyl]oxy]
      carbonyl]-L-glutamic acids (1c), their [[[2- and 3-substituted-4-[bis(2
      chloroethyl)amino]phenyl]oxy]carbonyl]-L- glutamic acids (1e-1), and the [[3
      substituted-4-[bis(2-chloroethyl)amino]phenyl]carbamoyl]-L- glutamic acids (1o-r)
      were synthesized. They are bifunctional alkylating agents in which the activating
      effect of the phenolic hydroxyl or amino function is masked through an
      oxycarbonyl or a carbamoyl bond to a glutamic acid. These prodrugs were designed
      to be activated to their corresponding phenol and aniline nitrogen mustard drugs
      at a tumor site by prior administration of a monoclonal antibody conjugated to
      the bacterial enzyme carboxypeptidase G2 (CPG2) in antibody-directed enzyme
      prodrug therapy (ADEPT). The synthesis of the analogous novel parent drugs (2a-r)
      is also described. The viability of a colorectal cell line (LoVo) was monitored
      with the potential prodrugs and the parent drugs. The differential in the
      cytotoxicity between the potential prodrugs and their corresponding active drugs
      ranged between 12 and > 195 fold. Compounds 1b-d,f,o exhibited substantial
      prodrug activity, since a cytotoxicity differential of > 100 was achieved
      compared to 2b-d,f,o respectively. The ability of the potential prodrugs to act
      as substrates for CPG2 was determined (kinetic parameters KM and kcat), and the
      chemical stability was measured for all the compounds. The unsubstituted phenols
      with different alkylating functionalities (1a-c) proved to have the highest ratio
      of the substrates kcat:KM. From these studies [[[4-[bis(2
      iodoethyl)amino]phenyl]oxy]carbonyl]-L-glutamic acid (1b) emerges as a new ADEPT
      clinical trial candidate due to its physicochemical and biological
      characteristics.

PMID- 8544183
TI  - Novel inhibitors for multidrug resistance: 1,3,5-triazacycloheptanes.
AB  - 1,3,5-Triazacycloheptanes were synthesized and examined for reversal of the
      multidrug resistance dependent on P-glycoprotein. Most of these compounds
      increased the intracellular uptake of vinblastine in multidrug-resistant mouse
      leukemia P388/ADR cells without influence upon the vinblastine accumulation in
      P388/S cells. The efficacy of 1,5-dibenzyl-1,3,5-triazacycloheptanes in
      increasing the vinblastine accumulation was in the order of 2,4-dithioxo (5) > 2
      oxo-4-thioxo (4) approximately 4-(methylthio)-2-oxo (6) > 2,4-dioxo (2). The
      efficacy was further increased when the benzyl group was converted to a
      chlorobenzyl group. Among these compounds, 6c [1,5-bis(4-chlorobenzyl)-1,5,6,7
      terahydro-4-(methylthio)-2H-1,3,5 - triazepin-2-one] potentiated the in vitro
      cell growth-inhibitory effect of vinblastine, adriamycin, and mitomycin C on
      P388/ADR cells and prolonged the life span of P388/ADR-bearing mice in combined
      therapy with vinblastine more than vinblastine alone.

PMID- 8544184
TI  - The myotubular myopathies: differential diagnosis of the X linked recessive,
      autosomal dominant, and autosomal recessive forms and present state of DNA
      studies.
AB  - Clinical differences exist between the three forms of myotubular myopathy. They
      differ regarding age at onset, severity of the disease, and prognosis, and also
      regarding some of the clinical characteristics. The autosomal dominant form
      mostly has a later onset and milder course than the X linked form, and the
      autosomal recessive form is intermediate in both respects. These differences are,
      however, quantitative rather than qualitative. Muscle biopsy studies of family
      members are useful in some cases, and immunohistochemical staining of desmin and
      vimentin may help distinguish between the X linked and autosomal forms.
      Determining the mode of inheritance and prognosis in individual families,
      especially those with a single male patient, still poses a problem. Current
      molecular genetic results indicate that the gene for the X linked form is located
      in the proximal Xq28 region. Further molecular genetic studies are needed to
      examine the existence of genetic heterogeneity in myotubular myopathy and to
      facilitate diagnosis.

PMID- 8544185
TI  - The molecular basis of ornithine transcarbamylase deficiency: modelling the human
      enzyme and the effects of mutations.
AB  - Human ornithine transcarbamylase is a trimer with 46% amino acid sequence
      homology to the catalytic subunit of E coli aspartate transcarbamylase. Secondary
      structure predictions, distributions of hydrophilic and hydrophobic regions, and
      the pattern of conserved residues suggest that the three dimensional structures
      of the two proteins are likely to be similar. A three dimensional model of
      ornithine transcarbamylase was generated from the crystal structure of the
      catalytic subunit of E coli aspartate transcarbamylase in the holoenzyme, by
      aligning the sequences, building in gaps, and minimising the energy. The binding
      sites for carbamyl phosphate in both enzymes are similar and the ornithine
      binding site in ornithine transcarbamylase appears to be in the same location as
      the L-aspartate binding site in aspartate transcarbamylase, with negatively
      charged side chains replaced by positively charged residues. Mutations in the
      ornithine transcarbamylase gene found in patients with hyperammonaemia of the
      "neonatal type" are clustered in important structural or functional domains,
      either in the interior of the protein, at the active site, or at the interchain
      interface, while mutations found in patients with milder "late onset" disease are
      located primarily on the surface of the protein. The predicted effects of all
      known missense mutations and in frame deletions in the ornithine transcarbamylase
      gene on the structure and function of the mature enzyme are described.

PMID- 8544186
TI  - Influence of the sex of the transmitting grandparent in congenital myotonic
      dystrophy.
AB  - To analyse the influence of the sex of the transmitting grandparents on the
      occurrence of the congenital form of myotonic dystrophy (CDM), we have studied
      complete three generation pedigrees of 49 CDM cases, analysing: (1) the sex
      distribution in the grandparents' generation, and (2) the intergenerational
      amplification of the CTG repeat, measured in its absolute and relative values,
      between grandparents and the mothers of CDM patients and between the latter and
      their CDM children. The mean relative intergenerational increase in the 32
      grandparent-mother pairs was significantly greater than in the 56 mother-CDM
      pairs (Mann-Whitney U test, p < 0.001). The mean expansion of the grandfathers
      (103 CTG repeats) was also significantly different from that seen in the
      grandmothers' group (154 CTG repeats) (Mann-Whitney U test, p < 0.01). This
      excess of non-manifesting males between the CDM grandparents' generation with a
      smaller CTG length than the grandmothers could suggest that the premutation has
      to be transmitted by a male to reach the degree of instability responsible for
      subsequent intergenerational CTG expansions without size constraints
      characteristic of the CDM range.

PMID- 8544187
TI  - Detection of hemizygosity at the elastin locus by FISH analysis as a diagnostic
      test in both classical and atypical cases of Williams syndrome.
AB  - A small pilot study has been carried out in order to assess the reliability of
      the detection of hemizygosity at the elastin locus by fluorescence in situ
      hybridisation (FISH) analysis, as a diagnostic test in both classical and
      atypical cases of Williams syndrome (WS). Five subjects with WS and five others
      in whom a diagnosis could not be confirmed on clinical criteria alone were
      evaluated. Hemizygosity at the elastin locus by FISH analysis was detected in all
      classical Williams syndrome cases and in three of the five atypical subjects.
      Furthermore, a combination of a few specific facial features found to be present
      in all subjects with the elastin gene hemizygosity has been suggested to aid the
      index of clinical suspicion.

PMID- 8544188
TI  - Absence of mutations in the promoter of the COL1A1 gene of type I collagen in
      patients with osteogenesis imperfecta type I.
AB  - Osteogenesis imperfecta type I results from decreased production of structurally
      normal type I collagen as a result of a COL1A1 "null" allele. Steady state
      amounts of COL1A1 mRNA are reduced in both the nucleus and cytoplasm of dermal
      fibroblasts from most affected subjects. Mutations involving key regulatory
      sequences in the COL1A1 promoter, such as the TATAAA and CCAAAT boxes, could
      alter steady state levels of mRNA, and therefore lead to this phenotype. To
      determine the frequency of such mutations in OI type I cell strains, we used PCR
      amplified genomic DNA in conjunction with denaturing gradient gel electrophoresis
      (DGGE) and SSCP, to screen the 5' untranslated domain, exon 1, and a small
      portion of intron 1 of the COL1A1 gene. In addition, direct sequence analysis was
      performed on an amplified genomic DNA fragment that included the TATAAA and
      CCAAAT boxes. Forty unrelated probands with OI type I, in whom no causative
      mutation was known, were included in the study. No mutations were included in the
      study. No mutations were identified in either the TATAAA or CCAAAT boxes in any
      of the affected people. In addition, there was little evidence of sequence
      diversity among any of the 40 subjects. These data suggest that mutations in the
      COL1A1 promoter do not play a significant role in the aetiology of OI type I.

PMID- 8544189
TI  - Analysis of triplet repeats in the huntingtin gene in Japanese families affected
      with Huntington's disease.
AB  - Huntington's disease (HD) is associated with the expansion of a CAG repeat in the
      huntingtin gene. Molecular analysis of the repeat in Japanese HD patients and
      normal controls was performed. The size of the CAG repeat ranged from 37 to 95
      repeats in affected subjects and from seven to 29 in normal controls. A
      significant correlation was found between the age of onset and the CAG expansion.
      The length of the expanded repeat is unstable in meiotic transmission and large
      increases occur in paternal transmission. At the same time the CCG repeat
      polymorphism adjacent to the CAG repeat was analysed and haplotypes of HD
      chromosomes were identified. Strong linkage disequilibrium was found between the
      CAG repeat expansion and an allele of (CCG)10 in Japanese HD chromosomes. It is
      distinct from that described previously in western populations. Western HD
      chromosomes strongly associate with an allele of (CCG)7. Possible mechanisms
      underlying the disequilibrium in Japan are discussed.

PMID- 8544190
TI  - Characterisation of germline mutations in the neurofibromatosis type 1 (NF1)
      gene.
AB  - Neurofibromatosis type 1 is one of the most common inherited disorders with an
      incidence of 1 in 3000. The search for NF1 mutations has been hampered by the
      overall size of the gene, the large number of exons, and the high mutation rate.
      To date, fewer than 90 mutations have been reported to the NF1 mutation analysis
      consortium and the details on 76 mutations have been published. We have
      identified five new mutations using single strand conformation polymorphism
      (SSCP) and heteroduplex analysis (HA) and three intragenic deletions with the
      microsatellite markers. Of the five new mutations, two were in exon 27a, two in
      exon 45, and one in exon 49 and these include 4630delA, 4572delC, R7846X, T7828A,
      and one in the 3' untranslated region (3' UTR). The two nucleotide alterations in
      exon 27a and the one in exon 45 are predicted to produce a truncated protein.

PMID- 8544191
TI  - Clinical features of nine males with molecularly defined deletions of the Y
      chromosome long arm.
AB  - Deletions of the long arm of the Y chromosome have previously been associated
      with azoospermia and short stature. We report the results of a detailed clinical
      and molecular study of nine males with partial deletions of Yq. Special emphasis
      was laid on congenital anomalies and dysmorphic features. Some of the patients
      have developmental problems or distinct facial features, namely a small chin and
      mouth, a high arched or cleft palate, downward slanting palpebral fissures, high
      nasal bridge, and dysmorphic ears. As far as we know, similar facial dysmorphism
      has not been previously described in association with del(Yq). These features are
      not, however, simply correlated to the size of the deletion. In none of these
      patients could evidence of aberrant Xq-Yq interchange be found.

PMID- 8544192
TI  - Twenty-four cases of the EEC syndrome: clinical presentation and management.
AB  - Twenty-four cases of EEC syndrome were identified as part of a nationwide study.
      Ectodermal dysplasia, by study definition, was present in all cases and hair and
      teeth were universally affected. Nail dysplasia was present in 19 subjects (79%)
      and the skin was affected in 21 (87%). The presence of hypohidrosis was not noted
      as a predominant feature in the syndrome and its occurrence appeared to depend on
      the presence of all other features. Distal limb defects from simple syndactyly to
      tetramelic cleft hand and foot were identified, including preaxial anomalies.
      Orofacial clefting was identified in 14 cases (58%) and lacrimal duct anomaly in
      21 (87%). Significant clinical problems encountered were chiefly cosmetic or
      ophthalmological, but conductive deafness and genitourinary problems in some
      cases required surgical intervention. Altered self-image was also noted in some
      cases. Multidisciplinary management is necessary with the early involvement of
      the clinical geneticist. Developmentally, the EEC syndrome and related disorders
      represent disorders of ectodermal/mesodermal interaction. Candidate regions
      include 7q21.3, the "ectrodactyly" locus; other candidates include developmental
      genes implicated in the ectodermal/mesodermal interactive process.

PMID- 8544193
TI  - Fetal valproate syndrome.

PMID- 8544194
TI  - Genotype-phenotype correlations of new causative APC gene mutations in patients
      with familial adenomatous polyposis.
AB  - Nine new causative mutations and seven previously characterised mutations of the
      APC gene of patients with familial adenomatous polyposis (FAP) were analysed for
      any genotype-phenotype correlations. The only clear genotype-phenotype
      correlation found was between the position of the mutation site and the presence
      or absence of congenital hypertrophy of the retinal pigment epithelium (CHRPE). A
      more distal mutation site was associated with an earlier age of onset of symptoms
      and a larger number of colonic polyps, but a notable amount of intrafamilial
      variation was observed.

PMID- 8544195
TI  - Mitochondrial DNA does not appear to influence the congenital onset type of
      myotonic dystrophy.
AB  - Neither the maternal inheritance pattern nor the early onset of congenital
      myotonic dystrophy are fully explained. One possible mechanism is that
      mitochondrial DNA (mtDNA) mutations might interact with the DM gene product,
      producing an earlier onset than would otherwise occur. We have used Southern
      hybridisation to show that high levels of major rearrangements of mtDNA are not
      present in muscle of five and in blood of 35 patients with congenital myotonic
      dystrophy. We used sequence analysis to show that no one particular mtDNA morph
      appears to cosegregate with congenital onset. A minor degree of depletion of
      mtDNA compared with nuclear DNA was present in the muscle of five patients with
      congenital DM, but we propose that this is not the primary cause of the muscle
      pathology but secondary to it. We have not found evidence that mtDNA is involved
      in congenital myotonic dystrophy.

PMID- 8544196
TI  - Refinement of the localisation of the X linked keratosis follicularis spinulosa
      decalvans (KFSD) gene in Xp22.13-p22.2.
AB  - X-linked keratosis follicularis spinulosa decalvans (KFSD) is a rare disorder
      affecting the skin and eyes. The disease was previously mapped in an extended
      Dutch family to Xp21.2-p22.2 between DXS16 and DXS269. Using five DNA probes and
      14 CA repeat polymorphisms spanning this region an extensive linkage study was
      performed in the same pedigree. The highest lod scores were 12.07 for DXS365 (pRX
      314) at 0 = 0, 11.72 for DXS418 (P122) at 0 = 0.015, and 10.93 for DXS989
      (AFM135xe7) at 0 = 0.045. Analysis of recombination events locates the gene for
      KFSD between AFM291wf5 and DXS1226 (AFM316yf5). This is region Xp22.13-p22.2, an
      area covering approximately 1 Mb. These data confirm and greatly refine the
      regional localisation of KFSD and greatly improve reliability of carrier
      detection.

PMID- 8544197
TI  - Unusual expression of Gaucher's disease: cardiovascular calcifications in three
      sibs homozygous for the D409H mutation.
AB  - Three sisters suffering from an unusual form of Gaucher's disease are described.
      These patients had cardiovascular abnormalities consisting of calcification of
      the ascending aorta and of the aortic and mitral valves. Neurological findings
      included ophthalmoplegia and saccadic eye movements in two patients, and tonic
      clonic seizures in the third. The three patients died, two of them after having
      undergone aortic valve replacement. Tissue was obtained from one of the sibs and
      fibroblast and liver beta-glucocerebrosidase activity was reduced to 4% and 11%
      of mean normal values. Genotype analysis indicated that the patient was
      homozygous for the D409H mutation. It is tempting to relate the phenotype of
      severe cardiac involvement to the D409H/D409H genotype, although further cases
      will be needed before this association can be confirmed.

PMID- 8544198
TI  - Vaginal rhabdomyosarcoma in a patient with Noonan syndrome.
AB  - This is the first report of a Noonan syndrome patient who has had a vaginal
      rhabdomyosarcoma. Recent reports of Noonan syndrome patients with leukaemia have
      prompted speculation that there may be a slightly increased malignancy risk
      associated with this syndrome.

PMID- 8544199
TI  - Monozygotic twins with chromosome 22q11 deletion and discordant phenotype.
AB  - We report monozygotic twins concordant for 22q11.2 deletion but discordant for
      clinical phenotype. Both boys show the typical dysmorphic features with short
      palpebral fissures, square nasal tip, small mouth, and both have nasal speech,
      but only one twin had a heart defect. They show that the phenotypic variability
      seen in this microdeletion syndrome cannot be explained on the basis of genotypic
      differences alone.

PMID- 8544200
TI  - Use of type VII collagen gene (COL7A1) markers in prenatal diagnosis of recessive
      dystrophic epidermolysis bullosa.
AB  - Generalised recessive dystrophic epidermolysis bullosa (EB) is a severe inherited
      disease in which patients suffer from blistering and scarring of the skin and
      mucous membranes after minor mechanical trauma. Tight genetic linkage has been
      established to the type VII collagen gene (COL7A1) at 3p21, with no evidence of
      locus heterogeneity. Several COL7A1 mutations have now been identified in
      recessive dystrophic EB patients. Prenatal diagnosis has been performed by
      examination of a fetal skin biopsy taken at about 16 weeks' gestation, and relies
      on identification of characteristic ultrastructural and immunohistochemical
      changes. We have now achieved a first trimester prenatal diagnosis using
      intragenic and flanking COL7A1 markers in a pregnancy at risk for recessive
      dystrophic EB. Segregation of the informative markers predicted the baby would be
      an unaffected carrier. The pregnancy continued to term and a healthy baby was
      born, confirming this result.

PMID- 8544201
TI  - Research in canine and human genetic disease.

PMID- 8544202
TI  - Prenatal diagnosis of X linked lymphoproliferative disease using multiplex
      polymerase chain reaction.

PMID- 8544203
TI  - A variant of Wiskott-Aldrich syndrome with nephropathy is linked to DXS255.

PMID- 8544204
TI  - Direct marketing of cystic fibrosis carrier screening: commercial push or
      population need?

PMID- 8544205
TI  - Approaching comparability and results of pulsatile flow in vitro testing of
      prosthetic heart valves.
AB  - The testing of prosthetic heart valves under pulsatile conditions is still a
      subject for debate among researchers and competent standardization bodies. The
      laboratory of Biomedical Engineering, of the Istituto Superiore di Sanita in
      Rome, has reproduced the current inter-laboratory situation with several test
      apparatuses, focusing on the definition of significant measurement parameters and
      procedures to obtain reasonably comparable data. The laboratory is also equipped
      with a Laser Doppler Anemometer (LDA) and a High-Speed Cinematographic system
      (HSC). A 29 mm tilting disc valve model, was mounted in the aortic position.
      Under tightly controlled system conditions the analyses performed on two pulse
      duplicators (PDs) may be deemed consistent for the valve model tested. Useful
      results, on the same valve specimen, are reported concerning velocity profiles
      and turbulent shear stress values (TSS). Furthermore valve motion on the
      Sheffield PD was monitored during the closing phase, and related cinematic data
      reported. The applied methodologies can provide relevant data to support surgeon
      decision making.

PMID- 8544206
TI  - Instrumentation of a mobilization couch for dynamic load measurement.
AB  - Spinal mobilization or manipulation techniques are frequently used by
      physiotherapists in the treatment of musculoskeletal disorders. Many of these
      techniques involve the application of a varying force to the affected joint.
      Despite the routine use of these techniques, there are no objective measures to
      quantify their use. This paper describes the principles of the instrumentation of
      a mobilization couch to enable measurement of the forces applied during
      mobilization of the lumbar spine. The couch was linked to a personal computer
      with a 286 processor and data card for data collection. The system was found to
      be reliable and sensitive over the range of forces applied during mobilization.
      It has potential for use in many situations where measurements of forces applied
      to the patient are required.

PMID- 8544207
TI  - Physical strain and mechanical efficiency in hubcrank and handrim wheelchair
      propulsion.
AB  - The physical strain and mechanical efficiency of manual wheelchair propulsion
      using handrim and hubcrank propelled racing wheelchairs were studied during a
      submaximal wheelchair exercise test on a stationary roller ergometer. Ten healthy
      male able-bodied subjects conducted two exercise tests in a random order and
      measurements of phyical strain (oxygen uptake, minute ventilation, respiratory
      exchange ratio, heart rate) and gross mechanical efficiency were obtained. During
      the experiment torque data, speed and power output were determined at a sample
      frequency of 0.1 Hz. Analysis of variance for repeated measures (p < 0.05) was
      used to establish differences. The hubcrank propulsion mechanism showed a
      significantly lower physical strain and higher gross mechanical efficiency in
      comparison with the handrim propulsion mechanism. The lower strain and higher
      efficiency in propelling the hubcrank partly seems to be due to the continuous
      biphasic cyclic propulsion movement, which allows both push and pull forces to be
      exerted. This involves flexor and extensor muscles around elbow and shoulder,
      leading to a reduced tendency to fatigue in individual muscles in the upper
      extremity. The more natural and neutral wrist-hand orientation also seems to
      diminish finger flexor activity and wrist-stabilizing muscle activity, and will
      thus reduce physical strain both with respect to the cardiorespiratory and
      musculoskeletal systems. The latter may influence the tendency to develop carpal
      tunnel problems positively. The reduced strain of the hubcrank propulsion
      mechanism clearly has a number of advantages over handrims for the human engine
      in the short and long run. However, technical innovation should address current
      practical problems of steering and braking. Clearly, hubcranks can be used in low
      seated wheelchairs (i.e. racing wheelchairs) only, and in subjects with a
      sufficiently large range of motion in the upper extremity. Moreover, the
      increased width is a drawback of hubcranks. Care should be taken while
      negotiating door posts.

PMID- 8544208
TI  - Tuberculosis into the next century. Proceedings of a symposium held on 4 February
      1995 at the Liverpool School of Medicine.

PMID- 8544209
TI  - Phosphorylcholine-containing antigens in bacteria from the mouth and respiratory
      tract.
AB  - Phosphorylcholine (PC)-containing antigens were sought in 269 bacterial isolates
      from the mouth and respiratory tract by an enzyme immunoassay method. Only 41
      (15%) isolates were PC-positive and of these 29 (70%) were strains of Haemophilus
      influenzae. Other species that produced positive results included two of five
      isolates of Gemella haemolysans, two of five isolates of Micrococcus spp., and a
      single strain each of Bacillus sp., Corynebacterium jeikeium, Lactococcus sp. and
      H. parainfluenzae. The presence of PC-containing antigens in H. influenzae may be
      an important source of cross-reaction in antigen detection techniques that detect
      the C-polysaccharide antigen of Streptococcus pneumoniae in respiratory specimens
      and would result in false positive results.

PMID- 8544210
TI  - Rapid differentiation of Prevotella intermedia and P. nigrescens by 16S rDNA PCR
      RFLP.
AB  - Prevotella intermedia and the newly described P. nigrescens cannot be reliably
      distinguished by phenotypic tests. In this study, restriction endonuclease
      digestion of amplified 16S rDNA (16S rDNA PCR-RFLP) was used to generate
      restriction profiles of the type strains of P. intermedia and P. nigrescens and
      43 fresh isolates identified as belonging to one of the two species. Whole-cell
      protein profiles were obtained by SDS-PAGE for comparative purposes. The type
      strains of P. intermedia and P. nigrescens were easily distinguished by 16S rDNA
      PCR-RFLP and the fresh isolates were assigned to either species on the basis of
      their restriction profiles. The identifications obtained were identical to those
      obtained by protein profiles. 16S rDNA PCR-RFLP is a rapid and reliable method
      for the differentiation of P. intermedia and P. nigrescens.

PMID- 8544211
TI  - Evaluation of a competitive ELISA method for the determination of Klebsiella O
      antigens.
AB  - Strains of Klebsiella spp. are often inagglutinable by O-specific antisera
      because of the copious capsule produced by most isolates. A competitive ELISA
      method based on the observation that bacterial supernates containing homologous O
      antigen specifically inhibited the reaction of type-specific antisera with
      purified LPS coated on ELISA plates was used to examine the O antigen of 82
      isolates of different Klebsiella species and subspecies. The O antigens O1/2ab
      (19 isolates), O2ab (13 isolates), O2ac (11 isolates) and O3 (16 isolates) were
      found to account for > 70% of the O antigenic types. Overall, 65 (79%) of the
      strains could be assigned to a specific O serogroup. The method is suitable for
      examining the role of individual O antigens in systemic klebsiella infections
      such as nosocomial septicaemia and pneumonia.

PMID- 8544212
TI  - Molecular typing of Salmonella enterica subsp. enterica serovar Enteritidis
      isolates.
AB  - A collection of 31 epidemiologically unrelated Salmonella enterica subsp.
      enterica serovar Enteritidis (S. Enteritidis) isolates obtained during a 12-year
      period was characterised by different molecular typing methods. Plasmid profile
      analysis, the detection of plasmid-encoded virulence genes and ribotyping allowed
      little or no further differentiation amongst these isolates. Two different
      hybridisation patterns were observed by IS200-typing of the S. Enteritidis
      isolates. However, pulsed-field gel electrophoretic separation of restriction
      endonuclease-digested whole-cell DNA provided a high level of discrimination
      amongst the 31 S. Enteritidis isolates. This could be increased by the
      comparative use of the three suitable restriction endonucleases XbaI, SpeI and
      NotI. Thus, pulsed-field gel electrophoresis proved to be superior in its
      discriminatory value to other molecular methods such as plasmid analysis,
      ribotyping or IS200-typing and represents a most helpful tool for the
      epidemiological typing of S. Enteritidis isolates.

PMID- 8544213
TI  - Characterisation of an enterotoxin-negative, cytotoxin-positive strain of
      Clostridium sordellii.
AB  - In ileal loop assay, ELISA and anion-exchange column chromatography, Clostridium
      sordellii strain 6018 was shown to produce a cytotoxin, but no detectable
      enterotoxin. DNA sequence and polymerase chain reaction analyses indicated that
      the lack of enterotoxin activity is not due to a lack of gene transcription, but
      to lack of a major portion of the enterotoxin gene. This is the first
      characterisation of such a strain.

PMID- 8544214
TI  - Lack of interference between IgA-binding proteins and IgA proteases of human
      pathogenic bacteria.
AB  - Some human bacterial pathogens produce specific immunoglobulin A1 (IgA1)
      proteases that cleave the heavy chain of human IgA1, generating intact Fab and Fc
      fragments. Other pathogenic bacterial species express surface proteins which bind
      to the Fc part of human IgA in a non-immune manner. To analyse whether IgA
      binding proteins affect the activity of IgA1 proteases, the ability of seven
      different IgA1 proteases to hydrolyse IgA1 in the presence of either of two
      different bacterial IgA-binding proteins was tested. Data obtained in two
      different types of experiment suggest that IgA1 bound to IgA-binding proteins
      still functions as a substrate for IgA1 proteases. As Fc fragments produced by
      cleaving IgA1 with IgA1 proteases still bind to IgA-binding proteins, we conclude
      that these two types of bacterial protein act independently of each other.

PMID- 8544215
TI  - Therapeutic use of an antibiotic-resistant Bifidobacterium preparation in men
      exposed to high-dose gamma-irradiation.
AB  - Five men received high-dose, uneven, whole-body gamma-irradiation by accidental
      exposure to an unshielded 137Cs source. Analysis of the faeces 9-12 days post
      irradiation showed low numbers of anaerobes and high counts of enterobacteria and
      staphylococci in four of the patients and total viable counts of < 10(3)/g in
      one. All five were treated with systemic ampicillin and gentamicin and oral
      nystatin commencing 4-7 days after irradiation. Three of the patients were also
      treated orally with a suspension of an antibiotic-resistant strain of
      Bifidobacterium longum for 30 days commencing 10-12 days post-irradiation. At 3
      weeks post-irradiation, B. longum had appeared in their faecal flora and total
      anaerobe counts exceeded those of facultative and obligate aerobes. At 4 weeks
      and 5-7 weeks post-irradiation, this normalisation of the faecal flora continued.
      In contrast, in the two patients who received a placebo the faecal flora was
      dominated by enterobacteria (Klebsiella, Enterobacter and Serratia spp.) showing
      multiple antibiotic resistance 3 weeks post-irradiation. These potential
      opportunist pathogens were not isolated from the B. longum-treated group. Only
      one patient in the control group survived beyond 3 weeks; he continued to show
      high faecal counts of enterobacteria and staphylococci and low counts of obligate
      anaerobes. 'Probiotic' treatment with this antibiotic-resistant strain of B.
      longum may be of benefit in the treatment of radiation sickness, aiding
      normalisation of the faecal flora and inhibiting colonisation and overgrowth with
      opportunist pathogens.

PMID- 8544217
TI  - Enterovirus specific IgM responses in children with acute and chronic paralytic
      syndrome.
AB  - Enterovirus specific IgM responses in 51 children aged 0-7 years with acute,
      clinically diagnosed paralytic syndrome and 8 children with chronic paralysis
      were detected by IgM antibody capture enzyme immunoassay. Twenty-nine out of 51
      (56.86%) acute phase sera were positive for enterovirus (Polio, CVB3 and CVA7)
      IgM antibodies, in 21 of whom poliovirus antibodies were found in close
      association with CVB3 and CVA7. On the other hand, preponderance of CVA7 specific
      IgM was detected in 6 out of 8 sera samples of chronically paralytic children.

PMID- 8544216
TI  - Changes in the anthropometric status of rural African under-fives during a decade
      of primary health care.
AB  - Protein energy malnutrition (PEM) is a major cause of hospital admissions and
      death in most impoverished Third World countries. In the Gelukspan Health Ward,
      in rural Western Transvaal, a primary health care (PHC) programme, based on the
      GOBI-FFF strategy, commenced in 1980. Community health surveys on African under
      five children were regularly undertaken. In 1990, to assess improvements
      achieved, anthropometric and other data were obtained on a representative series
      of 926 children. Harvard standards were used prior to 1984, and American NCHS
      reference standards thereafter. Low weight-for-age fell from 28 to 19%, low
      height for age from 33 to 17%, and low weight-for-height from 5 to 1%. The
      percentage with low arm circumference was unaffected, 3 and 4%, respectively. The
      improvements described are believed to be due in part to the PHC programme.
      Greater definition of the causes and extent of improvements are needed to
      optimize the State's present desire to intensify PHC, especially in rural areas.

PMID- 8544218
TI  - Soluble transferrin receptor as an index of iron status in Zairian children with
      malaria.
AB  - This study was designed to evaluate soluble transferrin receptor (sTfR) as an
      index of iron status in 0.5-16-year-old Zairian children: 17 with symptomatic
      malaria, 8 with asymptomatic malaria, and 15 controls. sTfR was also measured in
      20 plasma samples obtained from iron sufficient laboratory employees. sTfR,
      haemoglobin and ferritin were measured by enzyme-immunoassay, cyanmethaemoglobin
      method, and radioimmunoassay respectively. Mean haemoglobin levels were lower and
      ferritin higher (P < 0.001) in children with clinical symptoms of malaria than in
      those without malaria, and they were intermediate in those with asymptomatic
      malaria. Mean sTfR concentrations were similar among the three groups of children
      and laboratory controls. There was a considerable overlap in sTfR concentrations
      between the three groups of children (1.8-10.2, 2.9-11.6 and 2.97-8.95 mg 1(-1)
      in symptomatic malaria, asymptomatic malaria and control groups, respectively) as
      well as laboratory controls (1.2-7.30 mg l-1). Despite the overlap, 6 children
      with malaria (24%) and one control child (6.7%) had sTfR concentrations above the
      highest concentration found in laboratory controls. No child had serum ferritin <
      12 micrograms l-1 (suggestive of iron deficiency). As expected, sTfR negatively
      correlated with ferritin (r = -0.230) in the overall study population of
      children, and with haemoglobin in children with asymptomatic malaria (r = -0.943,
      P < 0.05), as well as in control children (r = -0.363). All children with sTfR
      above normal were also anaemic. Although the upper limit of normal sTfR
      concentration in healthy children is unknown, using the cut-off value of adults,
      we conclude that sTfR might be a more sensitive index of iron deficiency than
      serum ferritin in patients with malaria.

PMID- 8544219
TI  - Electron microscopy study of the mode of growth of Pseudomonas pseudomallei in
      vitro and in vivo.
AB  - The mode of growth of Pseudomonas pseudomallei in culture media and in the lung
      tissue of infected humans and animals was studied using transmission electron
      microscopy (TEM) and scanning electron microscopy (SEM). In culture media, P.
      pseudomallei cells were seen to be entrapped in microcolonies within large
      amounts of intercellular fibrous material. The lung tissue of infected humans and
      animals showed that bacterial cells growing in lung tissue were surrounded by
      radially arranged fibres that constitute a very well defined glycocalyx
      structure. In the infected areas of the animal lung tissue, bacterial cell could
      be seen to have formed glycocalyx enclosed microcolonies that displaced host cell
      components, e.g. the nucleus of a phagocyte. The presence of bacteria in unusual
      locations indicated that effective phagocytosis was not occurring. The
      demonstration that cells of P. pseudomallei produce exopolysaccharide
      glycocalyces and form glycocalyx enclosed microcolonies in laboratory media and
      in lung tissue of infected humans and animals and the presence of bacteria in
      unusual locations contribute to a new understanding of the mechanism whereby this
      organism can cause persistent chronic infections.

PMID- 8544220
TI  - Acute aphasia complicating typhoid fever in an adult.
AB  - Motor aphasia complicating bacteriologically confirmed typhoid fever in a 20-year
      old adult female is presented. Neither the cause of death nor the aetiology of
      this isolated neurological deficit could be determined from detailed post-mortem
      examination. An immune related mechanism is suggested based on the temporal
      characteristics of this complication and CSF abnormalities.

PMID- 8544221
TI  - Primary cutaneous nocardiosis caused by Nocardia otitidiscaviarum: two cases and
      a review of the literature.
AB  - We report two cases of primary cutaneous nocardiosis due to Nocardia
      otitidiscaviarum. The first case is a mycetoma, the second, a cutaneous abcess:
      these two cases were imported into France (Vietnam, Zimbabwe). The literature on
      primary cutaneous nocardiosis due to N. otitidiscaviarum is reviewed.

PMID- 8544222
TI  - Invasive mycosis of a pulmonary hydatid cyst in a non-immunocompromised host.
AB  - Fungal infection of a parasitic cyst is highly unusual. A case of invasive
      mycosis of a hydatid cyst situated in an ectatic bronchus is reported in a
      patient with normal immune status.

PMID- 8544223
TI  - Diabetes, obesity and hypertension in urban and rural people of bedouin origin in
      the United Arab Emirates.
AB  - In the United Arab Emirates, coronary heart disease has emerged as the leading
      cause of mortality over a 20-year period of rapid socioeconomic development. CHD
      risk factors of non-insulin dependent diabetes mellitus (NIDDM), obesity and
      hypertension were investigated by community based survey among a bedouin-derived
      Emirati population sample of 322 subjects (> or = 20 years). Diagnosis of
      diabetes was based on a random capillary blood glucose level > or = 11.1 mmol l
      1. Overall diabetes prevalence was 6% (11% in male and 7% in female subjects aged
      30-64 years). Urban residence was associated with higher blood glucose levels (P
      = 0.000), and with higher Body Mass Index (BMI) values (P = 0.002): 27% of all
      urban residents were obese (BMI > or = 30). The Shamsi were positively associated
      with higher blood glucose levels compared with other tribal groups (P = 0.000).
      Female gender was associated with higher BMI values (P = 0.000). Between 19 and
      25% of all subjects (male or female; urban or rural residents) have systolic
      hypertension (> 140 mm Hg). Male gender was associated with raised diastolic BP
      (P = 0.023). Diabetes was associated with higher mean systolic (P = 0.0274) and
      diastolic (P = 0.0132) BP levels. Differences in lifestyle between urban and
      rural residents are becoming blurred with further socioeconomic development and
      it is expected that the incidence of these CHD risk factors will continue to
      rise. Further studies are needed to specify changes associated with urbanization.
      Tribal influence also merits further study given the tradition of consanguinity
      in the UAE and the genetic basis to NIDDM.

PMID- 8544224
TI  - Saprophytic mycosis with pulmonary echinococcosis.
AB  - Two patients with pulmonary echinococcal hydatid cysts and concurrent saprophytic
      mycosis histologically resembling aspergillosis are described.

PMID- 8544225
TI  - Epidemic cholera in Latin America: spread and routes of transmission.
AB  - In the most recent epidemic of cholera in Latin America, nearly a million cases
      were reported and almost 9000 people died between January 1991 and December 1993.
      The epidemic spread rapidly from country to country, affecting in three years all
      the countries of Latin America except Uruguay and the Caribbean. Case-control
      studies carried out in Peru showed a significant association between drinking
      water and risk of disease. Cholera was associated with the consumption of
      unwashed fruit and vegetables, with eating food from street vendors and with
      contaminated crabmeat transported in travellers' luggage. This article documents
      the spread of the epidemic and its routes of transmission and discusses whether
      the introduction of the epidemic to Peru and its subsequent spread throughout the
      continent could have been prevented.

PMID- 8544226
TI  - Metacercarial precipitin test for diagnosis of human fascioliasis.
AB  - A metacercarial precipitin test was devised for diagnosis of human fascioliasis.
      The sera tested were those of cases of fascioliasis (acute and chronic), of
      schistosomiasis and of normal healthy individuals. Metacercariae were prepared in
      the laboratory from naturally infected snails. Serum dilutions of 1:5 (20%) and
      1:10 (10%) were incubated with metacercariae for periods of 6, 24 and 48 hours.
      No precipitation was observed when the sera of healthy persons were used. With
      sera of fascioliasis cases a precipitate was formed which increased in amount
      with time. It was more rapid in its formation and greater in its quantity with
      sera of acute fascioliasis. When incubation was prolonged a free precipitate was
      seen in the medium. With sera of schistosoma cases, a precipitate was observed in
      a few cases only; it was negligible in amount and localized to the plug area.
      Metacercarial precipitin is considered a simple, sensitive and specific test for
      diagnosis of human fascioliasis. It is recommended to use the serum in a dilution
      of 1:5 (20%), to give preliminary results after 6 hours incubation and to confirm
      24 hours later.

PMID- 8544227
TI  - Zoonotic intestinal parasites of hamadryas baboons Papio hamadryas in the western
      and northern regions of Saudi Arabia.
AB  - Six hundred and thirty-three faecal samples were randomly collected and examined
      for ova and cysts of intestinal parasites from five groups of hamadryas baboons
      of different population densities, with different human contact and in different
      ecological conditions (Al-Baha, Turabah and Al-Taif in south-western and Al-Rihat
      and Al-Akhal in north-western Saudi Arabia). Nine parasites were recorded
      (Giardia lamblia, Entamoeba histolytica, Escherichia coli, Balantidium coli,
      Enterobius sp., Trichuris sp., Hookworm, Hymenolepis nana and Schistosoma
      mansoni) in 274 samples (43.28%). The prevalence of parasites was high (36.0
      58.5%) in areas of mild, cool climatic conditions, where baboons were at high
      density and had maximum human contact. However, in an area (Al-Akhal) of hot, dry
      climatic conditions, low baboon density and minimum human contact, the parasites'
      prevalence was very low (9.5%). The concentration of parasites (ova or cysts per
      g of faeces) was medium. Post-mortem examination of 24, 20, 19 and 13 baboons
      from Al-Baha, Al-Taif, Turabah and Al-Rihat revealed most of the parasites
      recorded in random faecal samples at prevalence rates of 37.5, 30.0, 36.0 and
      23.0% respectively. The overall prevalence rate was 32.9%. Most of the parasites
      recorded in baboons were also recorded in humans in the areas of study.

PMID- 8544228
TI  - Polyparasitism in two rural communities with endemic Schistosoma mansoni
      infection in Machakos District, Kenya.
AB  - Formol-ether concentration supplemented by fresh saline smears was used to study
      intestinal parasites in two communities, Miu and Kitengei, in Machakos District,
      Kenya. These communities differed markedly in schistosome associated morbidity,
      in spite of similar prevalence and intensities of infection as revealed by Kato
      examination, Seven helminth and nine protozoan species were detected among 1011
      samples examined. More than 60% of the subjects were infected with more than one
      parasite: one had nine. Age-prevalence curves were typical for the different
      species, and overall prevalence of some protozoa, including Entamoeba spp. and
      Blastocystis hominis, exceeded that of the commonest helminth, Schistosoma
      mansoni. However, the observed prevalence of S. mansoni was barely 40% of that
      detected by Kato examinations. Strong associations were found between some pairs
      of protozoan species, but not with or among the helminths. The differences in the
      abundance and age-specific distribution of the other intestinal parasites at Miu
      and Kitengei were so small that it is unlikely that interactions between them and
      S. mansoni would account for the differences in schistosomal morbidity.

PMID- 8544229
TI  - Filarial vector studies in a diethylcarbamazine-treated and in untreated villages
      in Papua New Guinea.
AB  - Entomological studies were undertaken in three villages in the East Sepik
      Province of Papua New Guinea. The inhabitants of one village, Nanaha, had been
      treated with diethylcarbamazine (DEC) to reduce the prevalence and density of
      microfilaraemia of Wuchereria bancrofti. No intervention was undertaken in the
      other two villages, Yauatong and Musenau, in which bancroftian filariasis was
      present but with markedly different human prevalence rates and mean parasite
      densities. In Yauatong, infection rates in anopheline vectors (Anopheles
      punctulatus and An. koliensis) varied from 20.5 to 46.6% with infectivity rates
      of 0-1.4% while these rates were 10.9-14.3% and 0-1.1% respectively in Culex
      quinquefasciatus. In Nanaha after DEC treatment, infection rates were as high as
      16.3% in An. koliensis and infectivity rates reached 7.0% for An. punctulatus
      despite a 45% reduction in the number of people with detectable microfilariae
      (mf) and a 94% reduction in mf density in those who remained positive.

PMID- 8544230
TI  - Dot-ELISA for human leptospirosis employing immunodominant antigen.
AB  - A dot enzyme-linked immunosorbent assay which uses a proteinase-K resistant
      antigen (PK-Dot-ELISA) to detect antileptospiral IgM antibodies was compared to
      the microscopic agglutination test (MAT). The assay was evaluated in serum
      samples from patients with leptospirosis (n = 89), typhoid fever (n = 10),
      malaria (n = 19), syphilis (n = 20), hepatitis (n = 16) and clinically healthy
      individuals (n = 92). The PK-Dot-ELISA presented a sensitivity of 92.1% and a
      specificity of 97.5%. The overall results of the PK-Dot-ELISA were similar to
      those of the MAT. However, the PK-Dot-ELISA was capable of detecting antibody
      activity in 43% of acute-phase sera which were negative by the MAT. Our data
      suggest that PK-Dot-ELISA can be used as an important portable field
      serodiagnostic assay for acute leptospirosis.

PMID- 8544231
TI  - Evenoming by Bungarus multicinctus (many-banded krait) in Hong Kong.
AB  - We describe the clinical course of two cases of envenoming by the many-banded
      krait (Bungarus multicinctus). A man developed generalized paralysis and
      respiratory failure with transient hypertension. Nerve conduction studies
      revealed normal motor and sensory conduction velocities with reduced motor unit
      action potential amplitudes consistent with neuromuscular blockade. He showed a
      slight transient response to the banded krait (B. fasciatus) antivenom but
      required ventilatory support for 8 days. After the fourth day, there was some
      response to treatment with anticholinesterase. Another man developed diplopia,
      dysphagia and leg weakness but recovered spontaneously after 48 hours.

PMID- 8544232
TI  - Follow-up investigations on clinical manifestations after filariasis eradication
      by diethylcarbamazine medicated common salt on Kinmen (Quemoy) Islands, Republic
      of China.
AB  - From May to December 1993, a house-by-house survey was conducted on the changes
      in clinical manifestations of filariasis among 814 pre-control mf carriers in 88
      villages of five towns/districts on Kinmen Islands. Four hundred and sixteen
      (51%) pre-control mf carriers were examined physically with history taking. The
      rates of disappearance, improvement, no change, aggravation, and new occurrence
      were 72% (229), 6% (26), 14% (59), 6% (24) and 2% (8), respectively. The rates of
      disappearance and improvement were higher for the acute than for the chronic
      manifestations. However, these rates were also high for hydrocele and chyluria.
      These findings indicate that the acute manifestations disappear or greatly
      improve after filariasis eradication by a low dose of DEC medicated salt for a
      period of 6 months. However, the chronic ones remain unchanged or even aggravated
      to become one of the more important public health problems.

PMID- 8544233
TI  - Effective acidification of traditional fermented foods.
AB  - This study was carried out to investigate the survival rates of strains of
      enteropathogenic Escherichia coli in lactic and acetic acids and to compare them
      with their survival rates in sour porridge. The fermented and unfermented
      porridges were prepared in the laboratory. The fermented porridge had both lactic
      and acetic acids; unfermented porridge was adjusted to the pH of sour porridge
      with lactic and acetic acids. The sour porridge, the unfermented porridge
      adjusted to the pH of sour porridge with lactic and acetic acids and the
      unfermented porridge were inoculated with six strains of enteropathogenic E.
      coli. The inoculated porridges had a final concentration of 10(6)-10(7) colony
      forming units (c.f.u.) per ml of food. Few of the strains of enteropathogenic E.
      coli were detected 48 hours after inoculation in sour porridge. All the strains
      were detected 48 hours after inoculation in unfermented porridges adjusted to the
      pH of sour porridge with lactic and acetic acids but decreased in numbers of
      surviving cells by about 2 log10 c.f.u. per ml of food. All the strains survived
      in unfermented porridge for 48 hours and increased in numbers. These results show
      that lactic and acetic acids have antimicrobial properties but they are not as
      effective as sour porridge in inhibiting the growth and survival of
      enteropathogenic E. coli. The inhibitory property of sour porridge is due to a
      combination of many substances including lactic and acetic acids.

PMID- 8544234
TI  - Research methodology for developing efficient handwashing options: an example
      from Bangladesh.
AB  - Handwashing has been universally promoted for health interventions, but it is
      essential that the factors related to behaviour are understood in order to
      develop appropriate handwashing messages. We found the study of behaviour complex
      and had to combine several methods: in-depth interviewing, questionnaire;
      observational and bacteriological. Here we present our experiences in developing
      efficient handwashing options for rural Bangladesh. The components of handwashing
      practices after defecation of 90 rural women were studied (phase 1). During phase
      1 an in-depth interview was used to design the observational and questionnaire
      surveys. Behaviour was observed using a semi-structured record form and the
      effectiveness of the acts was measured by means of bacteriological tests. A
      questionnaire survey was undertaken on socioeconomic and water sanitation-related
      variables since they influence behaviour. Then, to develop efficient handwashing
      options, an experimental phase (phase 2) tested the bacteriological efficacy of
      the components found appropriate in phase 1. The effectiveness of the handwashing
      practices is believed to be poor since the bacteriological counts were found to
      be high (faecal coliform count of the left hand 1995, and of the right hand 1318
      colony forming units/hand). The practice comprised several components: use of an
      agent, handedness, frequency of rubbing, source and volume of rinsing water, and
      drying of the hands. Seventy-five per cent of the women reported that they could
      not afford soap. The experimental trials showed that soap, ash and soil give
      similar results under similar conditions of handwashing (faecal coliform counts
      of left hands: 195 (soap), 98 (ash), 129 (soil) and of right: 112 (soap), 54
      (ash) and 89 (soil) cfu/hand). The use of multi-method techniques in the study
      helped to understand and develop efficient handwashing options.

PMID- 8544235
TI  - Renal ultrasonography as a tool for detecting dynamic changes in blood pressure.
AB  - Renal ultrasonography has been used to assess renal blood flow under pathological
      conditions. We attempted to determine if sonographically derived renal resistive
      index measurements would be affected by subtle changes in flow as a consequence
      of transiently induced mild increases in blood pressure in persons with normal
      renal functioning. Nine subjects free of structural renal disease were studied
      with duplex Doppler ultrasonography. Main renal artery resistive indices were
      determined under resting baseline conditions and in response to graded infusions
      of phenylephrine sufficient to increase blood pressure by approximately 13/5 mm
      Hg. Change in blood pressure correlated with the change in main renal artery
      resistive index (r = 0.254, P < 0.05). Thus, the resistive index varies in
      association with transient increases in blood pressure and may reflect concurrent
      alterations in distal resistance under physiologic conditions.

PMID- 8544236
TI  - Monitoring the effacement of the uterine cervix by transperineal sonography: a
      new perspective.
AB  - The objective of this study is to monitor the process of effacement of the
      uterine cervix and demonstrate that transperineal sonography is the appropriate
      technique for this purpose. Eighty-six patients with normal, term pregnancies
      were studied at the beginning of labor. Transperineal sonography was performed in
      transverse and longitudinal planes. After the initial examination, patients were
      reexamined several times during a 1 to 4 hour period. We observed a progressive
      shortening of the canal and the synchronous opening of a funnel-shaped internal
      cervical os. When the funneling process reached the lower end of the cervix, both
      orifices fused, completing the process of effacement. The dilatation of the
      external os, which remained stationary during initial phase, increases very
      quickly once the effacement has been completed. Transperineal sonography
      efficiently imaged the changes described here.

PMID- 8544237
TI  - High resolution endoluminal ultrasonography in the staging of esophageal
      carcinoma.
AB  - Small catheters containing 20 MHz transducers have recently become available for
      high resolution endoluminal ultrasound. We report our early use of this technique
      to image and stage esophageal carcinoma. Fifteen patients undergoing high
      resolution endoluminal ultrasonography for suspected esophageal carcinoma were
      studied. Twelve of these patients also underwent computed tomography and
      pathologic correlation was available in seven. Satisfactory esophageal
      examination was possible in 14 of 15 patients. Of those with pathologic
      correlation, the depth of tumor invasion was correctly staged by high resolution
      endoluminal ultrasonography in six of seven patients and by computed tomography
      in only three of seven patients. Lymph node assessment correlated poorly with
      pathologic findings for both high resolution endoluminal ultrasound and computed
      tomography. With the increasing use of preoperative radiation therapy, we believe
      these early results predict a potential role for high resolution endoluminal
      ultrasonography in the staging of esophageal carcinoma.

PMID- 8544238
TI  - Transvaginal color flow imaging in the diagnosis of ovarian tumors.
AB  - Transvaginal ultrasonography and color flow imaging, performed to investigate
      whether there is any diagnostic advantage, were assessed over a 3 year period in
      217 patients with adnexal masses prior to explorative laparotomy. Gray scale
      sonography and color Doppler flow were performed 1 day prior to surgery. Benign
      tumors were found in 165 patients and flow was detectable in 82 (49.7%); 14
      patients had tumors of low malignant potential, 12 (85.7%) of whom showed
      detectable flow, and 38 had malignant tumors, in 25 (65.8%) of whom flow was
      detectable. Blood flow velocity was evaluated by the calculation of the
      resistance index prior to surgery. Mean resistive index was 0.39 +/- 0.05 for
      malignant tumors, compared with 0.49 +/- 0.06 and 0.55 +/- 0.07 for the low
      malignant potential and benign tumors, respectively. These differences were
      statistically significant (P < 0.01). When a resistive index of 0.47 was
      considered the cut-off value, the sensitivity was 88% and the specificity was
      calculated to be 85% (using color Doppler flow as the only diagnostic method).
      With our large cohort of patients, we demonstration the contribution of color
      Doppler flow examination in differentiating benign from malignant ovarian tumors
      prior to surgery.

PMID- 8544239
TI  - Influence of postprocessing curves on contrast-echographic imaging: preliminary
      studies.
AB  - The aim of this study was to evaluate the influence of postprocessing curves on
      the visual and quantitative enhancement of image brightness caused by the
      injection of a contrast agent. A fixed dose (0.45 ml/kg) of contrast agent
      EchoGen was injected into three dogs, and images of the kidney were investigated
      using one linear (A) and three nonlinear (B, C, D) postprocessing curves. Curve D
      gave the best gray scale images and was generally used for diagnostic imaging.
      Images were analyzed qualitatively in three dogs and quantitatively in one dog
      for brightness change caused by contrast agent injection. Visually the changes
      were most identifiable with curve C and least by curve D. Video intensity time
      curves reflected the qualitative changes. Peak contrast and area under the video
      density curve changed in the order curve D < curve B approximately curve A <
      curve C. Choice of the postprocessing curve can have a marked influence on the
      enhancement of image brightness by a contrast agent. Postprocessing curves
      optimized to display a wide range of echo levels may not always be an ideal
      choice for contrast sonography.

PMID- 8544240
TI  - Sonographic enhancement of renal cortex by contrast media.
AB  - The purpose of this study was to evaluate whether a phase shift contrast agent
      could enhance the renal cortex. Four doses of the contrast agent EchoGen ranging
      from 0.25 to 0.65 ml/kg were injected intravenously in three healthy dogs. Images
      of the kidney were recorded on a videotape before and after each injection. The
      images were evaluated visually and were computer-analyzed for brightness change
      caused by the contrast agent. Marked changes in cortical brightness were observed
      at the doses of 0.45 and 0.65 ml/kg. At lower doses the changes in image
      brightness were significantly reduced but measurable. The brightness peaked at 65
      +/- 9 seconds after injection and gradually decreased to the baseline value in
      approximately 12 minutes. The video density varied nonlinearly with dose, and at
      low doses its value drifted below the baseline. This is believed to be due to
      attenuation of echoes by the contrast agent. The results of this study indicate
      that the microbubbles formed by phase shift contrast media are sufficiently small
      and persist long enough to enhance sonographic images of the cortex. Contrast
      media whose effect is based on the phenomenon of phase shift permit enhancement
      of the gray scale characteristic of the kidney. The enhancements last up to
      several minutes and have strong potential to allow investigation of perfusion in
      kidney.

PMID- 8544241
TI  - Preovulatory sonographic uterine receptivity index (SURI): usefulness as an
      indicator of pregnancy in women undergoing assisted reproductive treatments.
AB  - To evaluate the uterine component as a determinant variable in the probability of
      establishing a pregnancy after assisted reproductive treatments, we introduced a
      mathematical formula derived from standard endovaginal uterine monitored color
      Doppler imaging parameters. We analyzed 102 cycles of ovarian stimulation with
      leuprolide acetate and exogenous gonadotropins resulting in 52 clinical
      pregnancies by stepwise logistic regression analysis. Sonographic endometrial
      pattern, thickness, diastolic blood flow, and resistive index variables were
      transformed into categorical variables and forced to yield a regression equation.
      Sonographic uterine receptivity index was calculated as a summation of four times
      endometrial pattern, five times resistive index, and two times diastolic blood
      flow. This index yielded values for each patient in a range of 0 to 15. Scores >
      or = 13 were associated with a successful outcome in 79.4% of the patients,
      whereas scores between 8 and 12 were accompanied by 45.8% pregnancy rates (P =
      0.01), and scores < or = 7 had successful treatment outcome in only 7.7% (P =
      0.0001). The scores obtained by this mathematical equation provide the ability to
      make reliable predictions about the outcome of assisted reproductive treatments
      in women undergoing ovulation induction with leuprolide acetate and human
      menopausal gonadotropins.

PMID- 8544242
TI  - Corpus luteum blood flow in normal and abnormal early pregnancy: evaluation with
      transvaginal color and pulsed Doppler sonography.

PMID- 8544243
TI  - Use of three-dimensional ultrasonography for the study of normal and pathologic
      morphology of the human embryo and fetus: preliminary report.
AB  - Our objective was to determine whether three-dimensional ultrasonography offers
      advantages over two-dimensional sonography for the evaluation of normal and
      pathologic morphology of human embryos and fetuses at various stages of
      pregnancy. Our studies suggest that small fetal and embryonic malformations are
      better defined with 3D sonography. Our experience indicates that 3D sonography
      allows more detailed visualization of fetal internal structures. We believe that
      with technical improvements 3D sonography will permit a more complete evaluation
      of fetuses earlier in gestation than is possible with current 2D sonographic
      instruments.

PMID- 8544244
TI  - "Fluid color" sign: a useful indicator for discrimination between pleural
      thickening and pleural effusion.
AB  - Color Doppler imaging has been applied traditionally in the evaluation of
      cardiovascular diseases. Recently it was observed that color signal may appear
      within the fluid collection in the pleural space during respiratory and cardiac
      cycles ("fluid color sign"). We performed this applicability of fluid color sign
      to the detection of pleural fluid capable of being removed to assess needle
      aspiration. From July 1992 to February 1994, we prospectively analyzed 76
      patients who were suspected of having minimal pleural effusion on the basis of
      their chest radiographs. All patients were examined by color Doppler
      ultrasonography for the presence of fluid color sign, which was followed by
      needle aspiration to verify the presence of pleural effusion. Among the 65
      patients with aspiratable fluid, 58 demonstrated positive fluid color sign
      (sensitivity 89.2%). None of the patients with solid pleural thickening showed
      fluid color sign (specificity 100%). With its relatively high sensitivity and
      specificity, the fluid color sign may be a useful diagnostic aid to real-time,
      gray scale ultrasonography for minimal or loculated effusion.

PMID- 8544245
TI  - Usefulness of color Doppler flow imaging in differential diagnosis of
      multilocular cystic lesions of the kidney.
AB  - Color Doppler flow imaging was carried out in 10 multilocular cystic lesions of
      the kidney. These consisted of three renal cell carcinomas, three hemorrhagic
      renal cysts, one benign multilocular cystic nephroma, two infected renal cysts,
      and one benign multilocular renal cyst secondary to von Hippel-Lindau disease. In
      the patients with renal cell carcinoma, color signals were obtained at the septum
      and in the solid component within the lesions. A pulsatile wave with a large
      maximum flow velocity and a high PI value was obtained in two of them. In one of
      the patients with hemorrhagic renal cysts, color signals were obtained at the
      region of the septum. In the other benign lesions, however, color signals were
      obtained only at the peripheral margin, and the flow waveform in these cases was
      identical to the waveforms found in the interlobar arteries. This study suggested
      that color display in the lesion well reflects its vascularity in patients with
      multilocular cystic renal diseases and that measurement of the systolic maximum
      flow velocity by fast Fourier transform analysis is useful for the differential
      diagnosis of malignant versus benign lesions.

PMID- 8544246
TI  - Color Doppler sonographic study of an iatrogenic fistula between the common
      carotid artery and internal jugular vein.

PMID- 8544247
TI  - Uhl's anomaly of the heart mimicking Ebstein's anomaly in utero.

PMID- 8544248
TI  - Horseshoe adrenal in Ivemark (asplenia) syndrome.

PMID- 8544249
TI  - Posterior fossa arachnoid cyst: an in utero mimicker of Dandy-Walker
      malformation.

PMID- 8544250
TI  - A limitation of carotid compression maneuvers.

PMID- 8544251
TI  - Failure to address the psychosocial benefit of prenatal sonography: another
      failing of the RADIUS Study. Routine Antenatal Diagnostic Imaging with
      Ultrasound.

PMID- 8544252
TI  - Leaving concert hall for clinic, therapists now test music's 'charms'.

PMID- 8544253
TI  - Female cybercadaver goes on-line; male counterpart gets a workout.

PMID- 8544254
TI  - Images gleaned at radiologists' annual meeting.

PMID- 8544255
TI  - From the Food and Drug Administration.

PMID- 8544256
TI  - From the Centers for Disease Control and Prevention. Case-control study of HIV
      seroconversion in health-care workers after percutaneous exposure to HIV-infected
      blood--France, United Kingdom, and United States, January 1988-August 1994.

PMID- 8544257
TI  - The AMA, tobacco, and the public health.

PMID- 8544258
TI  - The AMA, tobacco, and the public health.

PMID- 8544259
TI  - The AMA, tobacco, and the public health.

PMID- 8544260
TI  - The AMA, tobacco, and the public health.

PMID- 8544262
TI  - The AMA, tobacco, and the public health.

PMID- 8544261
TI  - The AMA, tobacco, and the public health.

PMID- 8544263
TI  - The tobacco industry and the Brown and Williamson documents.

PMID- 8544264
TI  - The tobacco industry and the Brown and Williamson documents.

PMID- 8544265
TI  - Weapons for protection in home invasion crimes.

PMID- 8544266
TI  - Weapons for protection in home invasion crimes.

PMID- 8544267
TI  - Pregnancy termination in relation to risk of breast cancer.
AB  - OBJECTIVE: To evaluate the association between pregnancy terminations and risk of
      breast cancer. DESIGN AND SETTING: Population-based case-control study in
      Wisconsin, Massachusetts, Maine, and New Hampshire. STUDY PARTICIPANTS: Cases
      were women younger than 75 years with a new diagnosis of breast cancer (n =
      6888), identified from statewide tumor registries. Controls younger than 65 years
      (n = 9529) were randomly selected from lists of licensed drivers, or for older
      subjects, from lists of Medicare beneficiaries. EXPOSURES AND OUTCOMES: Breast
      cancer risk in relation to spontaneous or induced abortions. RESULTS: After
      adjustment for parity, age at first birth, and other risk factors, pregnancy
      termination (induced or spontaneous) was associated with a relative risk (RR) of
      breast cancer of 1.12 (95% confidence interval [CI], 1.04 to 1.21), compared with
      the risk among women who had never had a termination. Induced terminations were
      associated with a RR of 1.23 (95% CI, 1.00 to 1.51), which was somewhat greater
      than the risk associated with spontaneous terminations (RR, 1.11; 95% CI, 1.02 to
      1.20). The association with induced abortions was stronger for those performed
      before legalization of abortion in 1973 (RR, 1.35; 95% CI, 1.01 to 1.80) than
      after this time (RR, 1.12; 95% CI, 0.84 to 1.49), suggesting a bias in reporting
      this sensitive procedure. CONCLUSIONS: A weak positive association was observed
      between abortion--whether induced or spontaneous--and risk of breast cancer. The
      increase in risk of breast cancer was somewhat greater among women with a history
      of induced terminations. However, this association may be due to reporting bias
      and was not significantly different than the slight risk for spontaneous
      terminations.

PMID- 8544268
TI  - The definition and preoperative prediction of clinically insignificant prostate
      cancer.
AB  - OBJECTIVES: To define clinically insignificant prostate cancer according to
      cancer volume, grade, cancer doubling time, and life expectancy; and to determine
      how many insignificant cancers are removed by radical prostatectomy. DESIGN AND
      PATIENTS: Clinically insignificant cancer was defined as a tumor that would give
      rise to no more than 20 cm3 of cancer within the prostate by the time of expected
      patient death (1990 life tables) and whose Gleason score was less than 4 in 40-
      to 49-year-olds, 5 in 50- to 59-year-olds, 6 in 60- to 69-year-olds, and 7 in 70-
      to 79-year-olds. Four definitions were formulated based on assumed cancer volume
      doubling times of 2, 3, 4, and 6 years. Using these four definitions, we reviewed
      337 totally embedded prostates removed at Mayo Clinic between 1991 and 1993 for
      clinical stage T1c through T3 cancer to determine how many contained clinically
      insignificant cancer. MAIN OUTCOME MEASURES: Clinically significant vs clinically
      insignificant prostate cancer. RESULTS: For cancer volume doubling time of 2, 3,
      4, and 6 years, clinically insignificant cancer was identified in one (0.3%), 13
      (3.9%), 25 (7.4%), and 49 (14.5%) of 337 prostatectomy specimens, respectively.
      CONCLUSIONS: Clinically insignificant prostate cancer can be defined by cancer
      volume, grade, cancer volume doubling time, and life expectancy of the patient.
      According to our definitions, most men treated with radical prostatectomy have
      clinically significant cancer.

PMID- 8544270
TI  - The challenges of emerging infectious diseases. Development and spread of
      multiply-resistant bacterial pathogens.
AB  - Resistance is an emerging problem in human medicine and the effects of resistance
      are being noted on an ever-increasing scale. Whether it is treatment of
      nosocomial bacteremia in New York City or community-acquired dysentery in Central
      Africa, multiresistant organisms are diminishing our ability to control the
      spread of infectious diseases. Clearly, the rate at which resistant organisms
      develop is not solely a function of the use of antimicrobials in humans, but is
      also highly influenced by the use of these agents in veterinary medicine, animal
      husbandry, agriculture, and aquaculture, as has been emphasized at recent
      meetings sponsored by organizations such as Rockefeller University and the
      American Society for Microbiology, and in the report on bacterial resistance
      recently issued by the US Office of Technology Assessment. We have entered an era
      where both physicians and patients must take on the responsibility to use
      antimicrobials wisely and judiciously. Just as in the days at the turn of the
      century when the public was an integral part of establishing quarantines for
      infectious diseases, now again the public's cooperation must be sought for this
      latest threat to public health. The multiresistant organisms of the 1990s are a
      grim warning of the possibility of the postantibiotic era.

PMID- 8544269
TI  - Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human
      influenza.
AB  - OBJECTIVE: The current study evaluated whether intranasal administration of the
      sialic acid analog 4-guanidino-Neu5Ac2en (GG167), an inhibitor of influenza virus
      neuraminidase, was effective and safe in either preventing or treating
      experimental human influenza. METHODS: Four randomized, double-blind, placebo
      controlled trials involving three prophylaxis limbs, two early treatment limbs,
      and one delayed treatment limb were conducted. SETTING: Isolation in individual
      rooms. PARTICIPANTS: Susceptible (serum hemagglutination-inhibition antibody
      titer < or = 1:8) adult volunteers (n = 166) were inoculated intranasally with
      10(5) TCID50 influenza A/Texas/91 (H1N1) virus. INTERVENTION: GG167, 3.6 to 16
      mg, was administered intranasally two or six times daily beginning 4 hours before
      inoculation (prophylaxis) or 1 or 2 days afterward (early or delayed treatment).
      MAIN OUTCOMES: Virological measures were frequency of infection based on viral
      shedding and/or seroconversion (prophylaxis) or quantitative viral shedding based
      on titers and duration of virus recovery (treatment). Clinical measures were the
      frequency of febrile illness and symptom severity scores. RESULTS: Intranasal
      GG167 was well tolerated for both prophylaxis and therapy. For all dose groups
      combined, GG167 prophylaxis was 82% effective in preventing laboratory evidence
      of infection and 95% effective in preventing febrile illness (P < .01 vs
      placebo). Early treatment with GG167 reduced peak viral titers by 2.0 log10, the
      median duration of viral shedding by 3 days, and the frequency of febrile illness
      by 85% (P < .05 for each comparison). Other measures of illness were reduced by
      approximately 50% to 70% in the GG167 dosing groups. Twice daily dosing was as
      effective as six times daily. CONCLUSIONS: Direct respiratory administration of
      the selective neuraminidase inhibitor GG167 appears safe and effective for both
      prevention and early treatment of experimental influenza. Influenza virus
      neuraminidase is important for viral replication in humans.

PMID- 8544271
TI  - Transmission of tuberculosis among the urban homeless.
AB  - OBJECTIVE: To determine the relative frequencies of primary and reactivation
      tuberculosis in the urban homeless. DESIGN: Prospective evaluation of homeless
      tuberculosis patients. SETTING: Central Los Angeles, Calif. PATIENTS: Thirty-four
      homeless patients with culture-proven tuberculosis. INTERVENTIONS: IS6110-based
      restriction fragment length polymorphism (RFLP) analysis was performed on
      Mycobacterium tuberculosis isolates. If results were inconclusive, pTBN12-based
      RFLP analysis was performed. MAIN OUTCOME MEASURE: Clustering of M tuberculosis
      isolates. A cluster consisted of two or more isolates with indistinguishable RFLP
      patterns. RESULTS: Twenty-four of 34 homeless patients had clustered isolates in
      six clusters. CONCLUSIONS: The minimum percentage of cases due to primary
      tuberculosis in the homeless was estimated to be 53%, compared with the
      traditional estimate of 10% in the general population. The results suggest that
      primary tuberculosis caused the majority of tuberculosis cases in this population
      of the urban homeless in central Los Angeles.

PMID- 8544272
TI  - Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta
      analyses.
AB  - PURPOSE: To resolve discrepancies in previous systematic overviews and provide
      estimates of the effect of stress ulcer prophylaxis on gastrointestinal bleeding,
      pneumonia, and mortality in critically ill patients. DATA IDENTIFICATION:
      Computerized search of published and unpublished research, bibliographies,
      pharmaceutical and personal files, and conference abstract reports. STUDY
      SELECTION: Independent review of 269 articles identified 63 relevant randomized
      trials for inclusion. DATA ABSTRACTION: We made independent, duplicate assessment
      of the methodologic quality, population, intervention, and outcomes of each
      trial. RESULTS: The source of discrepancies between prior meta-analyses included
      incomplete identification of relevant studies, differential inclusion of non
      English language and nonrandomized trials, different definitions of bleeding,
      provision of additional information through direct correspondence with authors,
      and different statistical methods. The current overview demonstrates that
      prophylaxis with histamine2-receptor antagonists decreases the incidence of overt
      gastrointestinal bleeding (odds ratio [OR], 0.58; 95% confidence interval [CI],
      0.42 to 0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22 to 0.88).
      There is a trend toward decreased overt bleeding when antacids are compared with
      no therapy (OR, 0.66; 95% CI, 0.37 to 1.17). Histamine2-receptor antagonists and
      antacids are associated with a trend toward lower clinically important bleeding
      rates than sucralfate is. There is a trend toward an increased risk of pneumonia
      associated with histamine2-receptor antagonists as compared with no prophylaxis
      (OR, 1.25; 95% CI, 0.78 to 2.00). Sucralfate is associated with a lower incidence
      of nosocomial pneumonia when compared with antacids (OR, 0.80; 95% CI, 0.56 to
      1.15) and histamine2-receptor antagonists (OR, 0.77; 95% CI, 0.60 to 1.01).
      Sucralfate is also associated with a reduced mortality rate (OR, 0.73; 95% CI,
      0.54 to 0.97) relative to antacids and to histamine2-receptor antagonists (OR,
      0.83; 95% CI, 0.63 to 1.09). CONCLUSIONS: Our results emphasize the need for
      registries to include all randomized trials and demonstrate the importance of
      explicit methodology for systematic reviews. There is strong evidence of reduced
      clinically important gastrointestinal bleeding with histamine2-receptor
      antagonists. Sucralfate may be as effective in reducing bleeding as gastric pH
      altering drugs and is associated with lower rates of pneumonia and mortality.
      However, the data are insufficient to determine the net effect of sucralfate
      compared with no prophylaxis.

PMID- 8544273
TI  - Addressing emerging microbial threats in the United States.

PMID- 8544274
TI  - World Health Organization strategy for emerging infectious diseases.

PMID- 8544275
TI  - Abortion and the risk of breast cancer. Is there a believable association?

PMID- 8544276
TI  - Appropriateness of routine chest radiography.

PMID- 8544277
TI  - Fresh vs preserved stool specimens for detection of parasites.

PMID- 8544278
TI  - Polyp surveillance in patients with limited life expectancy.

PMID- 8544279
TI  - [Opioid receptors altered binding nature in guinea-pig brain following the
      development of morphine dependence].
AB  - Morphine is well known to produce tolerance and dependence. The mechanisms for
      these phenomena are not clearly understood and there are a number of conflicting
      reports that chronic morphine administration decreases, increases, or leaves
      unchanged the number of opioid binding sites. We examined the potency of MScontin
      (oral controlled-release preparation of morphine) to induce morphine dependence
      and also determined the change of mu, delta and kappa opioid receptor types in
      brain homogenates obtained from morphine-dependent guinea-pigs. 1. Guinea-pigs
      were implanted subcutaneously with MScontin (300 mg.kg-1) and naloxone was
      employed to precipitate jumping behavior of withdrawal symptoms at various times.
      The highest degree of physical dependence was observed on the 2nd day after
      implantation. Therefore, this period was chosen to investigate opioid receptor
      binding assay. 2. Two days after implantation, the binding of 3H-DAGO (mu
      agonist), 3H-DPDPE (delta agonist) and 3H-U69593 (kappa agonist) to brain
      membranes prepared from morphine dependent and control guinea-pigs was
      determined. Scatchard plot of the saturation binding data revealed an increase in
      Bmax values (maximum specific binding) and no change in the Kd values
      (equilibrium dissociation constants) of 3H-opioid ligand bindings obtained from
      morphine-dependent animals as compared to controls. These results indicate that
      brain mu, delta and kappa opioid receptors are up-regulated in morphine dependent
      guinea-pigs.

PMID- 8544281
TI  - [Comparison of nerve damage with alcohol and that with phenol in guinea pigs].
AB  - We compared the damaging effect on myelinated nerve of alcohol and that of
      phenol. Guinea pigs of approximately 300 g in weight were used. Right sciatic
      nerve was exposed after intraperitoneal administration of pentobarbital. Saline
      was used in the first group as control. The second group received perineural
      administration of 100% alcohol. The third group received 100% alcohol inside the
      epineurium. The fourth group received perineural administration of 5% phenol in
      aqua. The fifth group received 5% phenol in aqua inside the epineurium. The first
      group showed no change. Toe necrosis was found in 2 cases in the second group, 3
      cases in the third, null in the fourth and 6 cases in the fifth group. We
      concluded that damage was larger with phenol than with alcohol when administered
      intraneurally, but the difference was not significant. Alcohol administered
      inside or outside of the epineurium made no significant changes, but phenol
      administered only inside the epineurium made a significant damage.

PMID- 8544280
TI  - [The effect of clonidine on the duration of vecuronium-induced neuromuscular
      blockade in humans].
AB  - The clinical duration of a bolus of vecuronium 0.1 mg.kg-1 was measured in two
      groups of patients between 31-55 years of age undergoing elective general
      surgery. Eight patients received no premedication and eight others clondine 4.0
      5.5 micrograms.kg-1 orally 90 minutes before arriving at the operating room.
      Neuromuscular blockade was continuously quantitated by recording the acceleration
      response to stimulation of the ulnar nerve train-of-four. Anesthesia was induced
      with thiamylal 5 mg.kg-1 and maintained with 50% nitrous oxide and isoflurane
      (Fet 0.5%) in oxygen. Supplementary doses of fentanyl (2 micrograms.kg-1 for the
      control group and 1 microgram.kg-1 for the clonidine group) were given before
      intubation and when anesthesia was considered to be insufficient. The clinical
      duration of vecuronium, defined as recovery to 25% of the control first twitch in
      the train-of-four sequence, was significantly longer in the clonidine group (51.2
      +/- 7.5 minutes compared with 40.5 +/- 5.1 minutes in the control group, P <
      0.01). In the duration of blockade there were no significant differences between
      groups for mean SBP, DBP and HR. Patients in the clonidine group required
      significantly less fentanyl to maintain hemodynamic stability. We conclude that
      clonidine prolongs the clinical duration of vecuronium by 26.4%, most probably by
      a pharmacokinetic interaction.

PMID- 8544282
TI  - [Changes in plasma cytokine levels during lung surgery].
AB  - We studied the changes in plasma cytokine (IL-6 and IL-8) levels during lung
      surgery in 20 patients. The correlation between the changes in cytokine levels
      and surgical stress as well as the postoperative complications were examined. The
      levels of IL-6 and IL-8 increased shortly after the surgical incision and were
      326 pg.ml-1 and 61 pg.ml-1 respectively, at the end of surgery. The changes in
      cytokine levels correlated well with the duration of surgery, blood loss and CPR
      levels for 2 days after the surgery. However, there were no severe postoperative
      complications in the present study. We conclude that the cytokines increase
      shortly after the surgical incision and the changes in cytokine levels correlate
      well with the surgical stress.

PMID- 8544283
TI  - [Comparison of temperatures from 7 points in the patients under intraperitoneal
      hyperthermic perfusion].
AB  - We measured the temperatures from 7 points in the patients under intraperitoneal
      hyperthermic perfusion (IPHP), associated with induced hypothermia. The
      temperatures from the 7 points were as follows, pulmonary artery blood
      temperature (PAT), bladder temperature (BT), sole deep body temperature (ST),
      forehead deep body temperature (FT), external aural cannal temperature (EAT),
      esophageal temperature (ET), and rectal temperature (RT). We studied the
      relationship between PAT and the other 6 temperatures. During IPHP, DT rose up to
      nearly 40 degrees C, and we considered it very useful to judge the temperatures
      of the other intra-abdominal organs, which were in contact with the perfusate of
      IPHP. Judging from the difference of PAT and ST, ST was found useful to estimate
      the degree of insufficiency of the peripheral circulation. We calculated the
      correlation coefficients with PAT among the four points, and the order of the
      correlation coefficients was EAT > ET > FT > RT. EAT showed the highest
      correlation coefficient with PAT (r = 0.981), and we considered EAT can be a
      substitute for PAT during IPHP. ET also showed a high correlation with PAT (r =
      0.959), but it showed an unusual rise in a case of hydrothorax with hot perfusate
      for IPHP. Therefore, ET cannot be used solely as a substitute for PAT, but ET can
      be used as a marker to find a complication of IPHP, hydrothorax.

PMID- 8544284
TI  - [Alterations of cardiac function and metabolism in the rat heart-lung preparation
      by methyl methacrylate (MMA) and their protection by ulinastatin].
AB  - We have assessed the deleterious effects of methyl methacrylate (MMA) on cardiac
      function and metabolism in the isolated heart-lung preparation and their
      protection by ulinastatin. Twenty-four male Wistar rats were prepared for the
      heart-lung model. They were randomly divided into 3 groups. In the MMA (M) and
      ulinastatin (U) groups, MMA 1000 micrograms.ml-1 was administered 7 minutes after
      the start of perfusion. At the end of the experimental period, the hearts were
      freeze-clamped and then myocardial high energy phosphates, lactate and glycogen
      were measured. Cardiac output decreased significantly in the M and U groups. Po2
      of the perfusion blood in the M and U groups was significantly lower than that in
      the control (C) group. Myocardial ATP in the M and U groups was significantly
      lower than that in the C group. ADP and AMP in the M and U groups were higher
      than those in the C group. Although there was no significant difference in
      lactate levels among the 3 groups, glycogen in the U and C groups was
      significantly higher than that in the M group. MMA 1000 micrograms.ml-1 is much
      higher than the blood level (0.05-31.89 micrograms.ml-1) reported clinically in
      patients who had femoral prosthesis. Ulinastatin increased myocardial glycogen
      content which had been reduced by MMA. This may suggest that ulinastatin has a
      protective effect on heart damaged by MMA.

PMID- 8544285
TI  - [Multiple regression analysis of pre- and intra-operative factors in relation to
      post-operative liver and renal functions].
AB  - We investigated the factors which may influence post-operative liver and renal
      function using a multiple regression analysis after isoflurane or sevoflurane
      anesthesia in 844 patients (ASA I or II, age 20-90 yr). Hepatic and renal
      surgeries were excluded from this study. The parameters examined were sex, age,
      degree of obesity, preoperative liver function, preoperative renal function,
      infection with hepatitis B or hepatitis C virus, inhalation anesthetics used,
      MAC.h of anesthesia, the duration of operation, blood loss, amount of blood
      transfusion, urine volume during operation, and surgical site. Serum GOT, GPT,
      total bilirubin, BUN and serum creatinine were examined on the 3rd and 7th day
      after surgery. An increase in serum GOT, GPT or bilirubin was observed for each
      of the following parameters; male, infection with hepatitis C virus, long
      operation, and upper abdominal surgery. Postoperative BUN and serum creatinine
      increased in patients with preoperative renal dysfunction, in elderly patients,
      and in hepatitis C carriers.

PMID- 8544286
TI  - [Changes in dementia rating scale scores of elderly patients with femoral neck
      fracture during perioperative period].
AB  - We evaluated changes in dementia rating scale scores in the revised version of
      Hasegawa's dementia scale (HDS-R), and rated dementia, 2 days before and 7 days
      after surgery in the elderly patients with femoral neck fracture. The 50 patients
      examined ranged in age from 70 years to 101 years. A perfect score in the HDS-R
      is 30 points, and a score below 20 points strongly suggests dementia. The results
      were as follows. In septuagenarian and octogenarian patients, the scale score was
      higher after surgery than the value before the surgery. Although the preoperative
      and postoperative scores of the patients who had been under epidural anesthesia
      were not significantly different, the score of patients who had been under
      general anesthesia was higher in the postoperative period than in the
      preoperative period. In octogenarian patients, there was a negative correlation
      between "postoperative score minus preoperative score" and "the number of the
      days from suffering fracture to surgery". These results showed that general
      anesthesia is more advantageous than epidural anesthesia from the viewpoint of
      the intellectual faculty in septuagenarian and octogenarian patients with femoral
      neck fracture, and it is within the bounds of possibility that the intellectual
      faculty may decline if an octogenarian patient is operated after a long delay
      from the occurrence of fracture. To prevent this decline, patients must be
      operated on as soon as possible.

PMID- 8544287
TI  - [Effects of nitrous oxide on electroencephalographic activity during sevoflurane
      anesthesia: a zero-crossing analysis].
AB  - We have investigated the influence of nitrous oxide (N2O) on central nervous
      system (CNS) during sevoflurane anesthesia by using zero-crossing method of EEG
      in 31 patients. The study was divided into three parts: Study 1 (n = 18), Study 2
      (n = 6) and Study 3 (n = 7). (Study 1) After induction of anesthesia, sevoflurane
      1.0 % in oxygen (O2), and sevoflurane 1.0 % with 67 % N2O in O2 were given to the
      patients sequentially in a random fashion, and EEG was recorded. (Study 2)
      Sevoflurane 1.7 % in O2, and sevoflurane 0.7 % with 67 % N2O in O2, which were
      considered to be the same anesthetic depth (= sevoflurane 1 MAC), were inhaled,
      and EEG was recorded in the same manner as in the study 1. (Study 3) We compared
      the effects of N2O on EEG during intravenous administration of fentanyl and
      midazolam with 67 % N2O, and without N2O, and EEG was recorded in the same
      manner. In all studies, percentage of each frequency range (delta, theta, alpha,
      beta) and average frequency were calculated by zero-crossing method. During
      sevoflurane anesthesia, the EEG activity was decelerated with N2O, depending on
      minimum alveolar concentration (MAC). But there were no significant changes in
      EEG activity of the patient with and those without N2O during intravenous
      anesthesia. We concluded that the influences of N2O on CNS can be evaluated by
      quantitative analysis of EEG.

PMID- 8544288
TI  - [Arterial plasma keton body levels during isoflurane anesthesia and surgery].
AB  - The authors measured arterial plasma levels of acetoacetate, 3-hydroxybutyrate,
      free fatty acid and the blood levels of lactate and glucose to evaluate fat
      metabolism during isoflurane anesthesia and surgery in twenty patients who ranged
      in age from 17 to 67 years. They underwent non-abdominal surgery (orthopedic
      surgery) or abdominal surgery (gastrointestinal or gynecological surgery). The
      operation started at 9 AM following starvation after 9 PM of the day before
      surgery. Anesthesia was induced with intravenous thiopental followed by
      intravenous succinylcholine to facilitate tracheal intubation, and maintained
      with isoflurane in 50 % nitrous oxide and 50 % oxygen. Vecuronium was given
      intravenously during surgery. Lactated Ringer's solution at a speed of 5-15 ml.kg
      1.h-1 was also administered intravenously throughout the procedures. Patients who
      had received glucose solution or blood transfusion were excluded. Plasma
      acetoacetate and 3-hydroxybutyrate levels increased significantly with surgical
      stimulation in both groups and they were slightly higher in the abdominal group
      than those in the non-abdominal group. However there was no statistical
      difference in plasma keton body levels between the groups. Mild increases in
      plasma free fatty acid and blood lactate levels were detected during surgery in
      both groups to the same extent. Blood glucose increased significantly during
      surgery in both groups and the increase was statistically higher in the abdominal
      group than that in the non-abdominal group. The findings suggest that there is no
      difference in fat metabolism between non-abdominal and abdominal groups during
      surgical intervention lasting as long as 3 hours when patients are starved and do
      not receive any glucose during surgery.

PMID- 8544289
TI  - [Efficacy of the artificial ventilation for the treatment of IgE-mediated
      anaphylactic shock in dog].
AB  - To evaluate efficacy of artificial ventilation with 100 % oxygen for treatment of
      IgE-mediated anaphylaxis, we compared survival of control ventilated dogs with
      one of dogs with spontaneous ventilation. Fourteen dogs sensitized to Toxica
      canis were randomly assigned to two groups: spontaneous respiration group (Group
      S, n = 8) and artificial ventilation group (Group A, n = 6). All dogs were
      anesthetized with pentobarbital. In Group S, all dogs breathed spontaneously with
      constant flow of 4 l.min-1 of oxygen. Spontaneous respiration maintained an end
      tidal CO2 level between 40 and 50 mmHg. In Group A, the dogs, paralyzed with
      pancuronium, were ventilated mechanically with 100 % oxygen, and the tidal volume
      was adjusted to maintain an end-tidal CO2 level between 35 and 40 mmHg. After
      measurements of pulmonary resistance (RL), dynamic compliance (Cdyn), and
      circulatory parameters at baseline, Ascaris suum antigen was administered
      intravenously into the systemic circulation to induce IgE-mediated anaphylaxis.
      RL, Cdyn and circulatory parameters were recorded continuously for 120 min after
      antigen challenge. Analysis of arterial blood gases was done throughout the
      study. Survival rates were 100 % and 50 % in Group A and Group S, respectively.
      In 7 of 8 dogs in Group S, apnea was observed during the period of 1 min to 5 min
      after antigen challenge, and the apnea continued during the period of 30s to 22
      min. Four dogs died during the period of 20 min to 30 min after antigen
      challenge. In both groups, RL increased significantly and Cdyn decreased
      significantly after antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544290
TI  - [The evaluation of cerebral oxygen balance during moderate hypothermic
      cardiopulmonary bypass].
AB  - The aim of this study was to evaluate cerebral oxygen balance during moderate
      hypothermic cardiopulmonary bypass (CPB). We measured jugular bulb venous oxygen
      saturation (SjO2), oxygen extraction ratio (O2 ER), glucose extraction ratio (Glu
      ER), and lactate production ratio (Lac PR) in 20 adult patients undergoing
      cardiac surgery. Fentanyl and midazolam anesthesia, alpha-stat blood gas
      management, non-pulsatile flow of 2.0-2.4 l.min-1.m-2, and moderate hypothermia
      were used in all cases. During cooling (at 34 degrees C of nasopharyngeal
      temperature), jugular-arterial blood difference of carbon dioxide partial
      pressure and O2 ER decreased, and SjO2 increased significantly. On the other
      hand, O2 ER increased, and SjO2 decreased significantly during rewarming (at 34
      degrees C). There were no significant changes in oxygen-glucose index, lactate
      glucose index, lactate-oxygen index, lactate production ratio, and lactate
      pyruvate ratio. Ten (50 %) of 20 patients who met reduced saturation criteria
      (defined as SjO2 < 55 %), showed significantly higher O2 ER and lower SjO2 than
      the non-reduced saturation group from postinduction to rewarming period. We
      conclude that cerebral venous reduced saturation represents a global imbalance in
      cerebral oxygen supply-demand-utility that may occur during rewarming period, and
      that the reduced saturation group represents a significant difference in cerebral
      oxygen balance during even stable hypothermic CPB. These episodes, however, are
      not associated with the acceleration of anaerobic glycolysis.

PMID- 8544291
TI  - [Density, specific gravity and baricity of various spinal anesthetics and those
      of normal human cerebrospinal fluid in Japanese].
AB  - We measured the density and specific gravity at room (20 degrees C) and body (37
      degrees C) temperatures of spinal anesthetic solutions, which have been
      commercially prepared in Japan. Solutions investigated were; (1) 0.4 % and 0.5 %
      tetracaine (T) in water, 0.5 % T in normal saline, 5 % glucose and 10 % glucose,
      (2) 0.3 % dibucaine in 5 % sodium chloride: (P), (3) 0.24 % dibucaine with 0.12 %
      tetracaine in 9.5 % glucose: (N); (4) 3 % lidocaine in 8.5 % glucose: (X); and
      (5) 0.5 % bupivacaine in water containing preservatives: (M). We also determined
      the density and specific gravity of normal human cerebrospinal fluid (CSF) in
      Japanese (n = 10) at 37 degrees C. Each local anesthetic solution was classified
      into hyperbaric, isobaric or hypobaric solution. Thirty seven centigrade 0.5 % T
      in normal saline and 37 degrees C 0.5 % M in water had the density comparable to
      37 degrees C human CSF and were considered to be relatively isobaric solutions.
      Our data demonstrated that human CSF had various densities. Therefore, it is
      possible that these isobaric solutions would vary their pharmacodynamic profiles
      in intrathecal use according to individual CSF characteristics and temperature of
      the solution.

PMID- 8544292
TI  - [The clinical usefulness and problem of combined spinal epidural needle].
AB  - The clinical usefulness of combined spinal-epidural needles, Portex
      Spinal/Epidural set (Pencil point tip type and Lancet point tip type), was
      evaluated on 30 patients undergoing orthopedic lower limb surgeries,
      hysterectomies or transurethral surgeries. In all the patients, the spinal
      epidural needles were successfully inserted with paramedian approach without any
      problem. The time to appearance of cerebrospinal fluid in the spinal needle hub
      after removal of the stylet was 15-40 seconds, and no patient in both groups had
      postspinal headache. Following spinal anesthesia, the local anesthetics injected
      through the epidural catheter extended the analgesia in the range of 1-2
      dermatomes higher in the Lancet point type group in comparison with Pencil point
      type group. It is possible that the hole in the dura may allow a transfer of
      local anesthetics into the subarachnoid space. The present study shows that
      combined spinal-epidural block is clinically useful, and the Pencil point type is
      safer than the Lancet point type.

PMID- 8544293
TI  - [Efficacy of epidural neurolysis].
AB  - Forty-one patients were treated with epidural neurolysis using 50 % ethyl alcohol
      2 ml. Thirty eight patients were suffering from cancer pain and three patients
      were complaining of chronic benign pain. Alcohol block was repeated 2.3 times
      (mean) in the same patient. Thirty patients were followed after the treatment.
      Forty-seven percent of the patients reported 70 % or greater pain relief and 20 %
      of the patients reported about 50 % pain relief. Duration of pain relief was from
      9 days to 203 days with a mean duration of 54 days. Adverse effects were reported
      43 % of the patients. There is no miserable adverse effect. Adverse effect
      reported most was pain with epidural injection of drugs after the alcohol block
      had been performed.

PMID- 8544294
TI  - [Anesthesia in a patient with history of multiple drug allergies].
AB  - A 38-year-old woman was admitted for intranasal ethmoidectomy. She had a history
      of serious anaphylactic reactions, including respiratory distress, hypotension
      and unconsciousness, to nonsteroidal anti-inflammatory drugs (Loxonin, Niflan)
      and antibiotics (Kefral, Minomycin). Preoperative intradermal skin tests against
      anesthesia-related drugs showed positive reactions to succinylcholine and
      vecuronium. After bilateral maxillary nerve block with 0.5 % bupivacaine
      (negative intradermal test) 3 ml, anesthesia was induced with diazepam, nitrous
      oxide, oxygen and sevoflurane. Trachea was intubated smoothly without muscle
      relaxants. Anesthesia was maintained with nitrous oxide, oxygen and sevoflurane
      0.5-1 %. The anesthesia and postoperative course of this patient were uneventful.
      To confirm the initiation of allergic reaction to anesthetics used in the
      patient, serum histamine, tryptase, and complement 1, 3 and 4 factors were
      measured at 3 points: preoperatively, immediately after the induction, and after
      extubation. They showed normal levels. These results showed that no allergic
      reaction occurred perioperatively. In conclusion, the valuable information was
      provided for the choice of anesthetics by thorough evaluation of the past history
      and intradermal testing.

PMID- 8544295
TI  - [Anesthetic management of a neonate with primary cardiac rhabdomyoma].
AB  - We have experienced anesthetic management for cardiac rhabdomyoma in a 21-day-old
      male, whose pulmonary trunk was obstructed by the tumor. He was anesthetized with
      fentanyl 70 micrograms.kg-1 and oxygen. The operative and post-operative courses
      were uneventful. Cardiac tumor, especially cardiac rhabdomyoma, in infant is
      rare. Anesthesia for the resection of the cardiac tumor must be carried out
      carefully, because sudden death due to arrhythmias as well as cardiac or
      respiratory failure is the most dangerous complication.

PMID- 8544296
TI  - [Coronary artery spasm as a cause of perioperative myocardial infarction and
      stunned myocardium].
AB  - We report a male patient who had recurrent coronary artery spasm on withdrawal
      from cardiopulmonary bypass, which led to myocardial infarction and stunned
      myocardium. The spasm responded to conventional medication. Transesophageal
      echocardiogram showed no remarkable asynergy during the operation. However, MB
      fraction of creatine kinase was 132 IU.l-1 and electrocardiogram showed new Q
      waves. After stopping intravenous catecholamines, hypokinesis of the anteroseptal
      segment appeared in the echocardiogram. Spotty myocardial necrosis and stunned
      myocardium might have resulted from recurrent coronary artery spasm.

PMID- 8544297
TI  - [The use of a laryngeal mask in a newborn infant with Nager acrofacial
      dysostosis].
AB  - A newborn female infant born at 41 week gestation with Nager acrofacial
      dysostosis had no congenital abnormalities in her parents and closed relatives.
      Her mother had uncomplicated pregnancy and normal delivery. Endotracheal
      intubation was attempted, because she developed apnea on her delivery, but it was
      not successful. She was transported immediately to our university hospital with
      mask ventilation. A laryngeal mask was placed after several trials of intubation,
      and ventilation was carried out successfully. We consider that the use of a
      laryngeal mask is one of the best ways in a case of difficult intubation.

PMID- 8544298
TI  - [A case of status asthmatics relieved by long-term inhalation of isoflurane].
AB  - A 58 year old man in status asthmatics refractory to drug therapy, was relieved
      by long-term isoflurane inhalation. In status asthmatics, it takes long time to
      recover from airway-damage, and inhalation-time will be prolonged in many cases.
      It is appropriate to use isoflurane because it is devoid of significant adverse
      effects compared with halothane and enflurane. Especially, isoflurane did not
      cause an increase in the serum fluoride revel, and will not lead to renal
      insufficiency in spite of its inhalation for 120 hours. It seems that isoflurane
      is suitable for long-term inhalation.

PMID- 8544299
TI  - [Problems of commercially available heparinized syringes in measurements of blood
      gases and electrolytes].
AB  - We compared the measured values of blood gases and electrolytes by commercially
      available heparinized syringes (PZ-II, Quick-lite and QS90) with normal and
      decreased calcium concentrations. With normal calcium concentration, the measured
      value of [Ca2+] in PZ-II was significantly less than that in Quick-lite and QS90,
      seemingly due to contained heparin. With hypocalcemia, the measured values of
      [Ca2+] in Quick-lite and QS90 were significantly greater than those in non
      heparinized syringe. The pH and PO2 decreased, and PCO2 increased as time passed.
      The [Ca2+] was suggested to be more influenced by heparin than by acid-base
      balance.

PMID- 8544300
TI  - [Effectiveness of the J-shaped LMA-holding forceps--F-forceps for LMA insertion].
AB  - F-forceps (Fukuhara's J Shaped LMA holding forceps) which enables correct
      laryngeal mask placement with ease was devised. Three methods using the forceps
      were tried in more than 1000 cases for administration of general anaesthesia. The
      results were compared with original Brain's method. The results were as follows;
      (1) Using F-forceps, success rate of proper placement without difficulties is
      much higher than with Brain's method, especially in F-III method with which 100%
      success was obtained. (2) After 7 trials, even beginners could shorten the time
      required for laryngeal mask placement by 10 seconds compared with their first
      trial. (3) Our method enables placement of the laryngeal mask without contacting
      patients. (4) One can master handling of the F-forceps with ease and shorten time
      necessary for placement of a laryngeal mask properly. (5) By applying F-II
      method, insertion of a laryngeal mask can be carried out without bending the
      patient's head. It is therefore suitable in patients with cervical vertebral
      injuries. F-forceps is considered to be highly useful for both anaesthesia and
      first aid.

PMID- 8544301
TI  - [Recent trend and future of intensive care medicine].

PMID- 8544302
TI  - [Clinical usefulness of neuromuscular monitor].

PMID- 8544303
TI  - [Molecular biological aspects for malignant hyperthermia].

PMID- 8544304
TI  - [Signal transduction systems of nerve growth cone: effects of anesthetics on the
      machinery].

PMID- 8544305
TI  - [Cloning and expression of cDNA for the opioid receptor].

PMID- 8544306
TI  - [Health care system in the 21st century].

PMID- 8544307
TI  - [Anesthetics and the glutamate receptor channels expressed in Xenopus oocytes].

PMID- 8544309
TI  - [Anesthetics and second messenger system--analysis using mRNA injected Xenopus
      oocyte].

PMID- 8544308
TI  - [Regulatory actions of general anesthetics on inhibitory receptor channels].

PMID- 8544310
TI  - [Role of alveolar epithelial cells in the repair process after lung injury].

PMID- 8544311
TI  - [Balanced anesthesia--historical aspect].

PMID- 8544312
TI  - [Balanced anesthesia (NLA) in the past].

PMID- 8544313
TI  - [The present state of balanced anesthesia--combination of intravenous and inhaled
      anesthetics].

PMID- 8544314
TI  - [Balanced anesthesia with epidural anesthesia].

PMID- 8544315
TI  - [Prospects of balanced anesthesia--combination with propofol].

PMID- 8544316
TI  - [Balanced anesthesia for postoperative management].

PMID- 8544317
TI  - [Prospects of balanced anesthesia--mainly focusing on combined induction of
      midazolam with barbiturate and epidural opioid with local anesthetics].

PMID- 8544318
TI  - [A research tool for autonomic nervous function: methodology and application of
      microneurography].

PMID- 8544319
TI  - [Closed claims analysis of anesthesia in Japan].

PMID- 8544320
TI  - [The quality improvement system at Hamamatsu University School of Medicine].

PMID- 8544321
TI  - [Active oxygen species: physiology and pathology].

PMID- 8544322
TI  - [Current topics of the artificial ventilation and respiratory management].

PMID- 8544323
TI  - [Anticancer therapy and anesthetic implications].

PMID- 8544324
TI  - [Brain protection--update].

PMID- 8544326
TI  - [Current view of malignant hyperthermia].

PMID- 8544325
TI  - [Cardiovascular interaction and anesthesia].

PMID- 8544327
TI  - [Recent trend and future in pain clinic in Japan].

PMID- 8544328
TI  - [Respiratory muscle functions: implications for anesthesia and critical care
      medicine].

PMID- 8544329
TI  - [Clinical application of statistics].

PMID- 8544330
TI  - [Epidural analgesia for surgery and postoperative pain].

PMID- 8544331
TI  - [Anesthetic management for endoscopic surgery].

PMID- 8544332
TI  - [An advanced anesthetic management for small children].

PMID- 8544333
TI  - [Significant role of carbapenem antibiotics: focused on meropenem (discussion)].

PMID- 8544334
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1990). I. Susceptibility
      distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 848 bacterial strains isolated from patients with urinary tract
      infections in 10 hospitals during the period of June 1990 to May 1991. Of the
      above total bacterial isolates, Gram-positive bacteria accounted for 23.9% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      76.1% and most of them were Escherichia coli. 1. Enterococcus faecalis:
      Ampicillin (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest
      activities against E. faecalis isolated from patients with urinary tract
      infections. The MIC90s of them were 2 micrograms/ml. Piperacillin (PIPC) was also
      active with the MIC90 of 4 micrograms/ml. The others were not so active with the
      MIC90s of 32 micrograms/ml or above. 2. Staphylococcus aureus: VCM and arbekacin
      (ABK) showed the highest activities against S. aureus isolated from patients with
      urinary tract infections. The MIC90s of them were 1 micrograms/ml. The others
      were not so active with the MIC90s of 32 micrograms/ml or above. 3. Escherichia
      coli: Cefozopran (CZOP), carumonam (CRMN) and ofloxacin (OFLX) showed the highest
      activities against E. coli isolated from patients with urinary tract infections.
      The MIC90s of them were of 0.125 microgram/ml or below. IPM, cefotiam (CTM) and
      cefmenoxime (CMX) were also active with the MIC90s of 0.25 micrograms/ml.
      Penicillins were not so active with the MIC90s of 32 micrograms/ml or above. 4.
      Klebsiella pneumoniae: Flomoxef (FMOX), cefixime (CFIX), CZOP and CRMN showed the
      highest activities against K. pneumoniae isolated from patients with urinary
      tract infections. The MIC90s of them were of 0.125 microgram/ml or below. IPM and
      gentamicin (GM) were also active with the MIC90s of 0.25 microgram/ml and 0.5
      microgram/ml, respectively. All other cephems were also active with the MIC90s of
      4 micrograms/ml or below. 5. Citrobacter freundii: GM and IPM showed the highest
      activities against C. freundii isolated from patients with urinary tract
      infections. The MIC90s of them were 1 microgram/ml. Amikacin (AMK) was also
      active with the MIC90 of 4 micrograms/ml. The others were not so active. 6.
      Enterobacter cloacae: IPM and GM showed the highest activities against E. cloacae
      isolated from patients with urinary tract infections. The MIC90s of them MIC90s
      of 0.5 microgram/ml. AMK and OFLX were also active with the MIC90s of 4
      micrograms/ml. Penicillins and cephems generally showed lower activities. 7.
      Proteus mirabilis: Most of the agents were active against P. mirabilis. Cephems
      were generally active with the MIC90s in a range of < or = 0.125 microgram/ml-4
      micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8544335
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1990). II. Background of
      patients].
AB  - Clinical background was investigated on 861 bacterial strains isolated from
      patients with urinary tract infections (UTIs) in 10 hospitals during the period
      from June, 1990 to May, 1991. 1. Distribution of sex, age and infections: Among
      over fifties males, the complicated urinary tract infections was most frequent.
      Among females, the uncomplicated urinary tract infections was most frequent
      without a relation of age. 2. Distribution of sex, age and pathogens isolated
      from UTIs: In uncomplicated UTIs, Escherichia coli was most frequently isolated
      without a relation of age. In complicated UTIs without indwelling catheter, E.
      coli and Enterococcus faecalis were isolated with a frequency of 20-30%,
      respectively. In complicated UTIs with indwelling catheter, Pseudomonas
      aeruginosa were most frequently isolated, and next E. faecalis. 3. Administration
      of antibiotics and pathogens isolated from UTIs: In uncomplicated UTIs and
      complicated UTIs without indwelling catheter, pathogens, after administration of
      antibiotics, isolated from patients have obviously decreased. In complicated UTIs
      with indwelling catheter, pathogens, before and after administration of
      antibiotics, isolated from patients were not decreased. And the distribution of
      pathogens after administration of antibiotics was similar.

PMID- 8544336
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1990). III. Secular changes in
      susceptibility].
AB  - Susceptibilities of Enterococcus faecalis, Citrobacter spp., Enterobacter spp.,
      Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa,
      Serratia spp. isolated from patients with urinary tract infections (UTIs) in 10
      hospitals during June 1990 to May 1991 to various antimicrobial agents were
      compared with those in the same period of previous years according to a
      classification, uncomplicated UTIs, complicated UTIs without indwelling catheter,
      and complicated UTIs with indwelling catheter. The susceptibilities of E.
      faecalis to minocycline (MINO) and ofloxacin (OFLX) has decreased. As for
      Citrobacter spp., Enterobacter spp. and P. mirabilis, which were detected very
      few in 1989 and 1990, their susceptibilities were not observed an obvious change.
      The susceptibilities of E. coli to MINO was observed a very clear alteration,
      that is, in uncomplicated UTIs and complicated UTIs, the susceptibilities has
      decreased. However, the susceptibilities of Klebsiella spp., P. aeruginosa and
      Serratia spp. were not observed an obvious variation.

PMID- 8544337
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1991). I. Susceptibility
      distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 751 bacterial strains isolated from patients with urinary tract
      infections in 11 hospitals during the period of June 1991 to May 1992. Of the
      above total bacterial isolates, Gram-positive bacteria accounted for 28.6% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      71.4% and most of them were Escherichia coli. 1. Enterococcus faecalis Ampicillin
      (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest activities against
      E. faecalis isolated from patients with urinary tract infections. The MIC90s of
      them were 2 micrograms/ml. Piperacillin (PIPC) and chloramphenicol (CP) were also
      active with the MIC90s of 8 micrograms/ml. The others were not so active with the
      MIC90s of 32 micrograms/ml or above. 2. Staphylococcus aureus including MRSA
      Arbekacin (ABK) showed the highest activities against S. aureus isolated from
      patients with urinary tract infections. Its MIC90 was 0.5 microgram/ml. VCM was
      also active with its MIC90 of 1 microgram/ml. The others were not so active with
      the MIC90s of 32 micrograms/ml or above. 3. Citrobacter freundii Ciprofloxacin
      (CPFX) showed the highest activities against C. freundii isolated from patients
      with urinary tract infections. Its MIC90 was 0.5 microgram/ml. IPM, gentamicin
      (GM), ABK and norfloxacin (NFLX) were also active with the MIC90s of 1
      microgram/ml. Penicillins and cephems were not so active. 4. Enterobacter cloacae
      IPM showed the highest activities against E. cloacae isolated from patients with
      urinary tract infections. Its MIC90 was 0.5 microgram/ml. CPFX was also active
      with the MIC90 of 2 micrograms/ml. Aminoglycosides were active comparatively. The
      MIC90s of them were 4 micrograms/ml. Penicillins and cephems generally showed
      lower activities. 5. Escherichia coli IPM and ciprofloxacin (CPFX) showed the
      highest activities against E. coli isolated from patients with urinary tract
      infections. The MIC90s of them were 0.125 micrograms/ml or below. Flomoxef
      (FMOX), cefmenoxime (CMX), cefuzonam (CZON), latamoxef (LMOX), norfloxacin (NFLX)
      and ofloxacin (OFLX) were also active with the MIC90s of 0.25 microgram/ml.
      Penicillins except mecillinam (MPC) were not so active showing the MIC90s of 32
      micrograms/ml or above. 6. Klebsiella pneumoniae IPM showed the highest
      activities against K. pneumoniae isolated from patients with urinary tract
      infections. Its MIC90 was 0.25 microgram/ml. Gentamicin (GM) and arbekacin (ABK)
      were also active with the MIC90s of 0.5 microgram/ml, respectively. But
      minocycline (MINO) and penicillins were not so active showing the MIC90s of 32
      micrograms/ml or above. 7. Proteus mirabilis Most of the agents were active
      against P. mirabilis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8544338
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1991). II. Background of
      patients].
AB  - Clinical background was investigated on 632 bacterial strains isolated from
      patients with urinary tract infections (UTIs) in 11 hospitals during the period
      from June, 1991 to May, 1992. 1. Distribution of sex, age and infections Among
      over forties males, the majority was taken by complicated urinary tract
      infections. Among females, the uncomplicated urinary tract infections was most
      frequent without a relation of age. 2. Distribution of sex, age and pathogens
      isolated from UTIs In uncomplicated UTIs, Escherichia coli was most frequently
      isolated without a relation of age, and next Enterococcus faecalis in over
      fifties. In complicated UTIs without indwelling catheter, E. coli and E. faecalis
      were isolated with a frequency of 17.4-26.6%, respectively. In complicated UTIs
      with indwelling catheter, E. faecalis were most frequently isolated, and next
      Pseudomonas aeruginosa. 3. Administration of antibiotics and pathogens isolated
      from UTIs In uncomplicated UTIs, pathogens, after administration of antibiotics,
      isolated from patients have obviously decreased from 319 to 34 isolates. And
      also, pathogens of complicated UTIs without indwelling catheter, have decreased
      from 122 to 49 isolates. However, in complicated UTIs with indwelling catheter,
      pathogens after or before administration of antibiotics, were not revealed an
      obvious change. 4. Pathogens and UTIs with or without factor and operation In
      uncomplicated UTIs with or without factor and operation, E. coli was mainly
      detected. In complicated UTIs without indwelling catheter and with or without
      factor and operation, E. faecalis and E. coli were mainly detected. In
      complicated UTIs with indwelling catheter and with factor and operation, E.
      faecalis and P. aeruginosa were detected, 24.3% and 22.9%, respectively. Without
      factor and operation, E. faecalis was detected 18.4%, and next Klebsiella spp.
      15.8%. And the distribution of pathogens after administration of antibiotics was
      similar.

PMID- 8544339
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1991). III. Secular changes in
      susceptibility].
AB  - Susceptibilities of Enterococcus faecalis, Citrobacter spp., Enterobacter spp.,
      Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa and
      Serratia spp. isolated from patients with urinary tract infections (UTIs) in 11
      hospitals during June 1991 to May 1992 to various antimicrobial agents were
      compared with those in the same period of previous years according to a
      classification, uncomplicated UTIs, complicated UTIs without indwelling catheter,
      and complicated UTIs with indwelling catheter. The susceptibilities of E.
      faecalis to cefmenoxime and amikacin has decreased. As for Citrobacter spp.,
      Enterobacter spp., P. mirabilis and Serratia spp., which were detected very few
      in 1989, 1990 and 1991, their susceptibilities were not observed an obvious
      change. The susceptibilities of E. coli to minocycline was observed a very clear
      alteration, that is, in uncomplicated UTIs and complicated UTIs without
      indwelling catheter, the susceptibilities has decreased. However, the
      susceptibilities of Klebsiella spp. was not observed an obvious variation. The
      susceptibilities of P. aeruginosa to quinolones isolated from uncomplicated UTIs
      has clearly decreased. These data should be considered in clinical treatment of
      various urinary tract infections.

PMID- 8544340
TI  - [Activities of antipseudomonal agents against clinical isolates of Pseudomonas
      aeruginosa].
AB  - Using clinically isolated 114 strains of Pseudomonas aeruginosa that were
      collected from April to October 1994, activity of antipseudomonal agents against
      these organisms was determined using the method of liquid microdilution. In
      addition, antimicrobial activities of the agents were graded according to
      serological groups of organisms. The results of this study are summarized as
      follows. 1. Many strains of P. aeruginosa were isolated mainly from sputum, pus
      and urine. 2. Serological group G organisms of sputum origin, group I of pus and
      bile origin, and group E of urine origin were isolated most frequently. 3. The
      most powerful antipseudomonal agent was cefclidin. Its MIC50 and MIC90 were 0.78
      and 6.25 micrograms/ml, respectively. The second most powerful agent was
      ciprofloxacin whose MIC50 and MIC90 were 0.39 and 12.5 micrograms/ml,
      respectively. 4. The proportions of resistant strains ranged from 0.9% for
      cefclidin to 40.4% for ofloxacin. The antipseudomonal agents to which 30% or more
      of strains were resistant were cefpirome, gentamicin and ofloxacin. 5. Cefclidin
      showed the most powerful activity against strains that were resistant to
      ceftazidime, imipenem, gentamicin and ofloxacin. Its MIC90 against all strains
      resistant to ceftazidime, gentamicin and ofloxacin was 6.25 micrograms/ml. The
      MIC90 of cefclidin and tobramycin against imipenem-resistant strains was 3.13
      micrograms/ml. 6. Group E organisms were found among strains resistant to
      ceftazidime, gentamicin and ofloxacin at high rates, but no group E strains were
      found among imipenem-resistant organisms. 7. Agents with highest activities by
      serological group of organisms were cefclidin against group A, tobramycin and
      ciprofloxacin against group B, imipenem against group E, ciprofloxacin against
      group G, and cefclidin and ciprofloxacin against group I.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8544341
TI  - [In vitro antibacterial activities of carbapenems and other antibiotics against
      Pseudomonas aeruginosa determined using low-amino-acid agar].
AB  - MICs of imipenem (IPM), panipenem (PAPM), cefozopran (CZOP), cefpirome (CPR),
      gentamicin (GM), tobramycin (TOB) and amikacin (AMK) against Pseudomonas
      aeruginosa were determined using Mueller-Hinton agar and low-amino-acid agar. On
      Mueller-Hinton agar, the antibacterial activity of TOB was superlative, followed
      in order by GM, CZOP, IPM, AMK, PAPM and CPR, whereas on low-amino-acid agar, the
      order changed to IPM, PAPM, TOB, CZOP, GM, AMK and CPR. The largest decrease of
      MICs was seen with PAPM on low-amino-acid agar, and the antibacterial activity of
      PAPM was not stronger than that of IPM. The growth of P. aeruginosa on the low
      amino-acid agar were significantly weaker than that on Mueller-Hinton agar, hence
      the evaluation of appearance colonies was difficult and misjudgement may result.
      Based on the above observations, we believe further investigations are needed
      before the application of low-amino-acid agar becomes routine.

PMID- 8544342
TI  - [Epidemic of cholera due to a new serogroup Vibrio cholerae O139 Bengal].

PMID- 8544343
TI  - [Monoclonal antibody mNI-58 inducing morphological changes in a human monocyte
      like cell line, U937, stimulated with phorbol myristate acetate (PMA)].
AB  - A mouse monoclonal antibody (mAb), designated mNI-58, was produced. The mNI-58
      markedly induced spread formation of the phorbol myristate acetate (PMA)
      stimulated U937 cells (referred to as PMA-U937 cells) but not that of the resting
      U937 cells. This spread formation was completely blocked in the presence of
      cytochalasin D or cycloheximide. It was partially blocked by an mAb against CD18
      (lymphocyte function-associated antigen-1 beta). These results suggest that mNI
      58 is capable of transducing a signal for spread formation of the PMA-U937 cells.

PMID- 8544344
TI  - [Studies on the pathogenicity of microbial proteases].

PMID- 8544345
TI  - [Discovery of epidermal cell differentiation inhibitor (EDIN) produced by
      Staphylococcus aureus and studies on the mode of action of EDIN].

PMID- 8544346
TI  - [Study on Pseudomonas transposons and molecular genetic analysis of Pseudomonas
      by use of transposons].

PMID- 8544347
TI  - [Helicobacter pylori urease].

PMID- 8544348
TI  - [Bacterial metalloproteases].

PMID- 8544349
TI  - [Campylobacter jejuni and autoimmune-mediated neurologic diseases: pathogenesis
      of Guillain-Barre syndrome and Fisher's syndrome].

PMID- 8544350
TI  - [Gastric mucosal lesion and free radicals].

PMID- 8544351
TI  - [Serum pepsinogen response to therapy for Helicobacter pylori associated gastro
      duodenal disease].
AB  - We investigated the effect of H. pylori therapy on serum concentrations of
      pepsinogens on 87 patients of gastro-duodenal disease. In addition, we intended
      to see whether serum pepsinogen can serve as markers of response to H. pylori
      eradication. In 48 successfully eradicated cases, there was a significant
      decrease in gastritis score, and was a significant fall in serum pepsinogen II
      (PG II) level, and was a significant increase in pepsinogen I/II ratio (PG I/II
      ratio). In contrast, no change in gastritis score, PG II, and PG I/II ratio were
      observed in 39 unsuccessfully eradicated patients. No change in serum pepsinogen
      I (PG I) level was observed in both groups. In provisional successfully
      eradicated cases in PG II of decrease greater than 30% in after treatment, there
      was a sensitivity of 83.3% and a specificity of 89.7%. For the PG I/II ratio of
      increased greater than 30% in after treatment, the sensitivity was 95.8%, and the
      specificity was 94.9%. These findings suggest that PG II, PG I/II ratio can be
      useful for clinical evaluation of eradication therapy.

PMID- 8544352
TI  - [Evaluation of gastric adaptive relaxation in isolated stomach from the guinea
      pig].
AB  - To evaluate the mechanism of gastric adaptive relaxation (GAR), we designed and
      established the experimental system for the measurement of GAR in isolated
      stomach from the guinea-pig by modifying the method of Desai. We also
      investigated the roles of non-adrenergic, non-cholinergic (NANC) nerves and
      endogenous nitric oxide (NO) in GAR by using this system. The rapid increase in
      the capacity of isolated stomach was observed over a certain pressure as GAR. GAR
      was abolished by tetrodotoxin (10(-6) M) in the presence of atropine (3 x 10(-6)
      M) and guanethidine (5 x 10(-6) M). NG-nitro L-arginine (LNNA) (10(-4) M), a NO
      synthesis inhibitor, also abolished GAR. L-arginine (10(-3) M), a precursor for
      NO synthesis, reversed LNNA-induced impairment of GAR. Sodium nitroprusside (10(
      6)-10(-4) M), a NO-donor, induced the gastric relaxation. These results suggest
      that GAR is mediated by NANC nerves, possibly via endogenous NO.

PMID- 8544353
TI  - [Detection of Helicobacter pylori by culture and the 13C-urea breath test using
      an automated breath 13C analyzer].
AB  - Up to now, the diagnosis of H. pylori infection has been made by the breath test
      using 13C-urea. In this study, 13C-urea breath samples were tested in 34 patients
      (peptic ulcer scar 17, chronic gastritis 17 cases) with an automated breath 13C
      analyzer (ABCA. Europa Scientific, Crewe, UK) and compared with the results of
      endoscopical diagnosis for H. pylori infection. Endoscopic and 13C-urea breath
      test (13C-UBT) were performed before eradicative medication. We described a
      modified protocol for the growth grade of H. pylori colonies in microbiology (H.
      pylori score), and for the delta 13C area under curve (AUC; permil*hr) obtained
      from each sample of expired breath. There was a significant correlation between
      delta 13C-AUC and the delta 13C level of each sample, but the correlation
      coefficient obtained at 10min (R2 = 0.582) was lower than that obtained at the
      other four time points (20min; 0.891, 30min; 0.949, 40min; 0.946, 50min; 0.946,
      60min; 0.820). The delta 13C-AUC well correlated with H. pylori score (p < 0.01),
      none of 26 H. pylori positive patients detected by culture was 13C-UBT negative
      (delta 13C-AUC < 8.2 permil*hr in mean + 2SD of H. pylori negative group). In
      conclusion, 13C-UBT using ABCA has high sensitivity and specificity, and it
      provides a non-invasive method for the detection of H. pylori urease activity.

PMID- 8544355
TI  - [A case report of epithelioid smooth muscle tumor (leiomyoblastoma) of the
      stomach prolapsing into the duodenal bulbus].

PMID- 8544354
TI  - [Management of polypoid lesions of the gallbladder by endoscopic ultrasonography
      (EUS)--a retrospective study to establish the diagnostic criteria and a
      prospective study to evaluate its reliability].
AB  - The diagnostic criteria of endoscopic ultrasonography (EUS) in the management of
      polypoid lesions of the gallbladder was established by a retrospective study
      using 57 cases with polypoid lesions of the gallbladder that were all resected
      and confirmed histologically. By this study, EUS findings of polypoid lesions of
      the gallbladder were classified into the following six groups; Type I with a
      foamy high echogram, Type II with a globular high echogram, Type III with a
      papillary high echogram, Type IV with a papillary solid echogram, Type V with a
      nodular solid echogram and Type VI with a nodular solid echogram including
      multiple spotty an-echoic areas which suggested the presence of Rokitansky
      Aschoff sinus. Comparing the types of EUS findings with histological diagnosis,
      Type I and II corresponded to cholesterol polyps. Type III and IV contained
      benign pseudo tumors such as cholesterol polyp or hyperplastic polyp as well as
      tumorous lesions such as adenocarcinoma or adenoma. Type III with over 10 mm in
      size and IV with over 5 mm in size had a possibility of tumorous lesions. Type V
      usually corresponded to adenocarcinoma, and Type VI to adenomyomatous
      hyperplasia. From these results, the following criteria was established; (1)
      Polypoid lesions showing Type I, II, III with less than 10 mm in size, IV with
      less than 5 mm in size and VI should be followed-up as benign diseases. (2)
      Polypoid lesions of Type III with over 10 mm in size and IV with over 5 mm in
      size was considered to be relative indications for surgery as tumors. (3)
      Polypoid lesions of Type V was an absolute surgical indication as malignant. The
      reliability of this EUS criteria was followingly evaluated by a prospective study
      using 94 cases with polypoid lesions of the gallbladder; 32 cases with open or
      laparoscopic cholecystectomy and 62 cases with over one year follow-up
      observations. The criteria corresponded well with the histological or follow-up
      findings in Type I, II, III with less than 10 mm in size, IV with less than 5 mm
      in size, V and VI. It had, however, a tendency of over indications to surgery in
      Type III with over 10 mm in size and IV with over 5 mm in size because these
      types were widely set not to overlook tumorous lesions such as adenoma and small
      adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8544356
TI  - [Lemmel's syndrome caused by a giant diverticulum in the third portion of the
      duodenum, report of a case].

PMID- 8544357
TI  - [A case of arteriovenous malformation of the ileum complicated with decompensated
      liver cirrhosis: effective case of home parenteral nutrition for intestinal
      bleeding].

PMID- 8544358
TI  - [A case report of autoimmune hepatitis with Felty's syndrome].

PMID- 8544359
TI  - [A case of hepatic myelolipoma].

PMID- 8544360
TI  - [A case of hepatocellular carcinoma presumably transforming to malignant spindle
      cell tumor].

PMID- 8544361
TI  - [A case of acalculous acute cholecystitis caused by allergy].

PMID- 8544362
TI  - [A case of pancreas carcinoma observed reflux of the bile juice on cut surface of
      the pancreas].

PMID- 8544363
TI  - [Persistence of polarization in self-generated attitude change].
AB  - The present study examined the persistence of polarization in self-generated
      attitude change, and explored the possibility of an additional polarization. In
      Experiment 1, a judgment about a traffic accident case was made, in which the
      defendant tended to appear guilty. Subjects in Thought condition then made a
      second judgment after thinking about the case for six minutes. In Experiment 2,
      two months later, the Thought subjects made judgments of the case again. The
      results were as follows: Judgments tended to polarize after the six-minute
      interval, and the effect persisted to the second experiment. However, a second
      polarization did not occur when another interval of six minutes to think about
      the case was provided. Some relationship between harshness of judgment and the
      number of reasons given for harsh judgment was found. The results were discussed
      in terms of both informational influence and social comparison.

PMID- 8544364
TI  - [The assessment of individual differences in self-control in daily life].
AB  - Two studies were conducted to develop an instrument to assess individual
      differences in self-control in daily life. In Study 1, a 20-item Redressive
      Reformative Self-Control Scale (RRS) was developed through a study involving 529
      subjects. RRS consists of three sub-scales: "redressive self-control (RDSC)"
      which assesses a tendency of using a repertoire to resume normal functions that
      have been disrupted; "reformative self-control (RFSC)" which measures one's
      tendency to force oneself into a stressful situations for the sake of larger and
      more meaningful rewards in the future; and "external control". The validity of
      two sub-scales (RDSC, RFSC) was confirmed in Study 2. Fifty-one subjects selected
      on the basis of RDSC and RFSC scores were interviewed about self-control in their
      everyday lives. The findings indicated the importance of a combination of
      redressive and reformative functions in successful self-control. It was suggested
      that these two functions be examined for the assessment of individual differences
      in self-control in daily life.

PMID- 8544365
TI  - [Populational differences of vocal behavior in Japanese monkeys].
AB  - This study suggested the possibility of vocal learning in the Japanese monkey
      (Macaca fuscata) by examining populational differences in the calls of
      individuals from two populations, the Ohirayama and Yakushima. Genetic
      variability of these two populations is very small. Japanese monkeys emit a class
      of contact calls known as the "coo" call. The coo calls of 41 subjects (30
      animals from the Ohirayama group and 11 animals from the Yakushima group) were
      analyzed spectrographically. There are significant differences between the two
      groups in four parameters of coo calls (minimum frequency, start frequency,
      duration to the maximum frequency, and total duration). Individuals in the
      Ohirayama group emit coo calls lower in frequency and longer in duration than
      those in the Yakushima group. The results suggest the possibility that the
      populational differences of coo calls are due to learning.

PMID- 8544366
TI  - [Emergence of cooperation in one-short prisoner's dilemmas and the role of
      trust].
AB  - The main purpose of this study is to apply the "selective play paradigm" to
      explain how cooperation emerges in one-shot prisoner's dilemmas. A unique feature
      of the selective play paradigm is the option for not playing a PD game. For this
      purpose, a computer simulation of 100-actor groups was conducted. At the
      beginning of each replication, each simulated actor was randomly assigned to one
      of eleven levels of trust, which indicates the actor's estimate of the overall
      cooperation rate in the group. Each simulated actor, then, decided whether or not
      to interact with the previous partner based on the calculated expected gains from
      interacting with one of the other partners. Results of the simulation show that:
      (1) when substantial opportunity costs exist, having a high level of trust
      benefits the actor; (2) the above effect of trust depends on the actor's
      cooperativeness in PD games; (3) but does not depend on the overall cooperation
      rate in the group.

PMID- 8544367
TI  - [Two types of facial impression judgments and recognition memory for faces].
AB  - The author investigated the semantic processing advantage effect on facial
      recognition memory using two types of personality traits and two types of
      recognition tests. In Experiment 1, based on the personality impression ratings
      for smiling and neutral faces made by 40 subjects, four expression-independent
      (i.e., intelligent, reliable, determined, and ambitious) and four expression
      dependent (i.e. extroverted, friendly, affectionate, and likeable) personality
      trait words were selected. In Experiment 2, two groups of 22 subjects (expression
      dependent trait group and expression-independent trait group) were asked to rate
      32 faces in terms of physical features or personality traits. This was followed
      by an unexpected yes-no recognition test in which identical pictures of the
      target faces or the same person's expression-changed faces were randomly
      presented with distractor faces. In identical-picture recognition condition, the
      semantic processing advantage emerged in both expression-dependent and expression
      independent trait groups, whereas in expression-changed recognition condition the
      advantage appeared only in expression-independent trait group. It was discussed
      that the semantic-codes explanation would be plausible to explain the results
      obtained.

PMID- 8544368
TI  - [Analysis of temporal factor affecting hepatic illusion of a rotated disk].
AB  - Twenty-four subjects experienced Cormack's illusion by rotating a disk using
      fingers of both hands with some pauses inserted during the rotation. Variables
      were durations for rotating a disk and pause. The illusion magnitude was measured
      just before each pause. The first experiment showed that the illusion magnitude
      decreased with increasing the pause. The second experiment showed that there was
      no difference in illusion magnitude between 5- and 20-second conditions of pause
      for 20-second rotating duration, although the magnitude was smaller for 20-second
      pause than that for 5-second pause under the condition of 5-second rotating
      duration. The experiment also showed that the final magnitude did not depend on
      whether the magnitude was measured every five seconds or only once at the end of
      the rotation. The results indicate that pause during rotation contributes to
      recovering from adaptation due to the rotation and that the effect of pause
      depends on the duration of rotation. The results also indicate that the
      increasing illusion magnitude with time is not an artifact due to the method of
      measuring the magnitude.

PMID- 8544369
TI  - [Effects of intimacy and familiarity on self-assertive strategy in interpersonal
      conflicts among preschool children].
AB  - The purpose of this study was to investigate the effects of interpersonal
      relations on self-assertive strategy. One hundred and thirty-four preschool
      children, 70 boys and 64 girls between five and six years old, were asked a set
      of questions concerning how they would feel and behave when a peer provoked them.
      The peer intimacy and familiarity were systematically varied, and the main
      results were as follows: High-intimacy/high-familiarity group chose self
      assertive strategies more frequently than High-intimacy/low-familiarity group,
      and Low-intimacy/low-familiarity group chose self-assertive strategies more often
      than Low-intimacy/high-familiarity group. It was also found that the self
      assertive strategy they would choose depend on the intimacy and familiarity of
      the peer. Implications of the findings for social cognitive ability and self
      regulation of preschool children were discussed.

PMID- 8544370
TI  - [The structure of self in Japanese culture: aspects and age differences].
AB  - A questionnaire was administered to college students and adult members of society
      to tap the structure and content of self that are characteristic of Japanese
      culture. The items measured some of the constructs that presumably characterize
      self in Japanese culture: namely, "amae" (Doi, 1971), "Japanese ego" (Minami,
      1983), and "Kanjinshugi" (Hamaguchi, 1982). Factor analysis found eight factors,
      which were classified into two aspects: social and individualistic. These two
      aspects both included universal and culture-specific factors, and the universal
      factors appeared to correspond fairly well to Markus and Kitayama's (1991)
      "interdependent and independent construals of the self". College students see
      more importance in the social aspects of the self than adults in both universal
      and culture-specific factors. On the individualistic side, however, they rated
      themselves as being less independent in the universal factors, but more
      exclusively egocentric in the other factors. The findings were discussed in terms
      of the development of self of young adults in Japan.

PMID- 8544371
TI  - [Effects of organizational strategy and development on recall of subject
      performed tasks (SPTs)].
AB  - Free and cued recall of subject-performed tasks (SPTs) and verbally-presented
      sentences were tested with children of nine, 11, 13 years of age. In the SPTs
      condition, subjects performed mini-tasks (e.g., put on a hut) and memorized them.
      Results indicated that recall was higher for SPTs than for sentences, and that
      age affected the recall of sentences but not of SPTs. Beneficial effects of
      category cues were observed only for the 11- and 13-year-old age groups in the
      SPTs condition. These results were discussed in terms of the development of an
      organizational strategy.

PMID- 8544372
TI  - [Use of static pressure-volume relations to estimate the total amount of
      pulmonary connective tissue--theoretical approach].
AB  - There is no accepted way to estimate the amount of connective tissue in the lungs
      in vivo. I propose an equation for estimating the total amount of pulmonary
      connective tissue from static pressure-volume relations. The stress-strain
      relations of pulmonary connective tissue were assumed to be describable by a non
      linear exponential function: f = exp(ax)-1, where "f" is stress, "x" is strain,
      and "a" is Young's modulus of elasticity. The connective tissue elements were
      assumed to be distributed randomly in orientation within a pulmonary lobule, and
      the bodies of a pulmonary lobule were assumed to be packed in "equilibrium space
      division", as proposed by Suwa (1981). Stochastic geometry for elastic elements
      in the lung was used to obtain a set of equations describing the static pressure
      volume relationship, such that P = (0.12 zeta 0/3V0) x [exp(ax)/(1 + x)2] and V =
      V0 (1 + x)3, where V0 is a reference lung volume in a perfectly relaxed state and
      zeta 0 is the total amount of connective tissue in the pulmonary parenchyma. This
      new model can accommodate static pressure-volume relations of human subjects in
      the range of relatively high lung volumes reported by Turner et al. (J App
      Physiol 25: 664, 1968), by Corbin et al. (Am Rev Respir Dis 120: 293, 1979), and
      by Finucane et al. (J App Physiol 26: 330, 1969). In conclusion, the total amount
      of connective tissue in lung parenchyma can be estimated with this new model of
      the static pressure-volume relationship at relatively high lung volumes.

PMID- 8544373
TI  - [Effects of plasma albumin on theophylline concentration in lung tissue].
AB  - To study the relationship between plasma and lung tissue theophylline
      concentrations, we changed the number of binding sites for theophylline on serum
      albumin. Cefazoline, which competes with theophylline for those binding sites,
      was given to rats, and free theophylline was separated by ultrafiltration. The
      dose of cefazoline was directly related to the percentage of free theophylline
      and was inversely related to the plasma total theophylline concentration. The
      plasma free theophylline concentration, however, was unchanged at the lower doses
      of cefazoline and was low only at the highest dose. The concentration of
      theophylline in lung tissue was inversely related to the dose of cefazoline. The
      concentration of 1, 3-dimethyluric acid, a major metabolite of theophylline, was
      also inversely related to the dose of cefazoline, which suggests that the
      metabolic rate of theophylline did not increase. Excretion of theophylline via
      the urine might be accelerated by its diuretic action. We conclude that when the
      binding of theophylline to plasma proteins is altered in rats, the concentration
      of free theophylline in plasma does not reflect the concentration of theophylline
      in lung tissue. Instead, the total theophylline concentration in plasma can be
      used as an index of the concentration in lung tissue.

PMID- 8544374
TI  - [Role of neutrophils in lung injury after intestinal ischemia and reperfusion in
      dogs].
AB  - We studied the role of neutrophils in lung injury after intestinal ischemia and
      reperfusion (I/R) in anesthetized dogs with lung lymph fistulae. One group was
      subjected to 2.5 hours of balloon occlusion of the superior mesenteric artery
      without laparotomy, followed by 3 hours of reperfusion (I/R group, n = 7). The
      other group was subjected to the same procedures, except for intestinal I/R (sham
      operation group, n = 6). In the sham operation group, lung fluid balance,
      hemodynamics, extravascular water volume (Qw 1: ml/g BFDW), myeloperoxidase
      activity in the lung (MPO: unit/g DW), H2O2 production by neutrophils in blood
      (mean DCF/cell), and migration of neutrophils into the lung lymphatic system did
      not significantly change. In the I/R group, both lung lymph flow (Jv) and protein
      clearance (Qp) increased more than 2.5 fold as compared with the baseline values,
      while capillary pressure (Ppc) and the ratio of lymph to plasma protein
      concentration (CL/Cp) remained almost the same as the baseline values. Qw1 also
      moderately increased. MPO activity, H2O2 production, and migration of neutrophils
      into the lung lymphatic system increased after I/R, and were more remarkable than
      in the sham operation group. These results suggest that activation and migration
      of primed neutrophils contributes to lung injury after intestinal ischemia and
      reperfusion.

PMID- 8544375
TI  - [Genetic analysis by fluorescence in situ hybridization of lung cancer cells
      obtained by bronchial brushing].
AB  - Fluorescence in situ hybridization was done with specimens obtained by bronchial
      brushing from 25 patients with abnormal lung shadows. A satellite DNA probe,
      specific for chromosome 11, was used to detect numerical chromosome aberrations
      in tumor cell nuclei. Normal diploid human lymphocyte nuclei, which served as
      control, had two signal spots in 99.6% of the nuclei in response to the
      chromosome 11 probe. The most frequent signal spots in class V cells (Case 1-7)
      ranged from 3 to 5, followed by 6 to 8, regardless of histopathological findings
      of lung cancer. In class I cells (cases 8-11) the signal appearance was similar
      to that in class V cells. The disease in patients from whom class I cells were
      obtained was found to be malignant by other diagnostic procedures performed
      afterward. The abnormalities in cases 13-25 were diagnosed as non-malignant by
      brush cytology, and clinical course showed a little more than 3 spots. These data
      indicate that fluorescence in situ hybridization with specimens obtained by
      bronchial brushing can be useful for detecting numerical chromosome abnormalities
      and can aid in the rapid diagnosis of lung cancer.

PMID- 8544376
TI  - [Microorganisms cultured from sputum and blood in association with episodes of
      fever during anti-cancer therapy in patients with lung cancer].
AB  - We examined the clinical features and significance of pathogenic microbes
      isolated from sputum and blood of patients with lung cancer during anti-cancer
      therapy. Pathogenic bacteria were more likely to be isolated from patients with
      episodes of fever than from afebrile patients. The major species of bacteria
      isolated from sputum were Staphylococcus aureus, including methicillin-resistant
      strains, and Gram-negative bacilli, which are known to be frequently involved in
      hospital-acquired infections. The presence of an indwelling central venous
      catheter for intravenous hyperalimentation was an important risk factor for the
      development of a febrile episode, which indicates that bacteremia was a major
      cause of fever. In one quarter of the blood cultures from the patients with
      persistent fever, various species of pathogenic microbes were recovered, one
      third of which were fungi. Bacteriological examinations done before and after the
      introduction of granulocyte-colony stimulating factor (G-CSF) revealed that
      strains of Klebsiella spp. decreased and those of methicillin-resistant S. aureus
      increased. There was no firm evidence that G-CSF decreased the incidence of
      episodes of fever. However, remains G-CSF may a allow the dose intensity of anti
      cancer agents to be increased, which would lead to severe leukocytopenia.
      However, more detailed investigation is needed to clarify the role of G-CSF
      against bacterial infection during anti-cancer therapy.

PMID- 8544377
TI  - [Relations between chest CT and pathologic findings in pulmonary infarction
      associated with lung cancer].
AB  - Chest radiographic (mainly CT), and pathological findings in pulmonary infarction
      associated with lung cancer were studied to obtain information useful for the
      interpretation of CT findings, and to help determine the cause of infarction.
      Sixteen cases of lung infarction were chosen from among 518 cases of lung cancer.
      All patients were operated on between January 1980 and December 1990. Sixteen
      surgical cases and one autopsy case all with evidence of lung cancer and
      infarction were chosen. There were 13 men and 4 women with a mean age of 56
      years. Adenocarcinoma was found in 8 cases, squamous cell carcinoma in 6,
      adenosquamous carcinoma in 2, and small cell carcinoma in 1. Chest radiographs
      and CT revealed infarction shadows in 8 of the 16 cases. Typical CT findings for
      pulmonary infarction were: shadows located in the same lobe and periphery as the
      cancer; ill-defined, 10-25 mm nodular shadows; and lesions located both in the
      subpleural zone and apart from the pleura. Lesion counts in each area were about
      the same. Observation of one patient for 2 months revealed a decrease in the size
      of the nodular shadows and clarification of their margins. In most cases,
      centrally extended cancer resulted in vascular stenosis and infarction.

PMID- 8544378
TI  - [Daytime pulmonary hypertension in the obstructive sleep apnea syndrome].
AB  - Patients with obstructive sleep apnea syndrome (OSAS) may have daytime pulmonary
      hypertension (PH). Transient and sometimes severe elevations of pulmonary
      arterial pressure during sleep as a result of intermittent upper airway
      obstruction may lead to daytime PH. We sought to study the factors involved in
      the development of daytime PH. Right-heart catheterization, pulmonary function
      tests, and arterial blood gas measurements were done in 25 patients in whom OSAS
      was diagnosed by whole-night polysomnography. Eight of the patients (32%) had PH,
      defined by a mean pulmonary arterial (PA) pressure > or = 20 mmHg. For the group
      as a whole, mean PA pressure was positively and significantly correlated with
      daytime PaCO2 (r = 0.79), percent of ideal body weight (r = 0.45), and Hb (r =
      0.40). Mean PA pressure was negatively and significantly correlated with PaO2 (r
      = -0.54), FEV 1% (r = -0.52), and %FVC (r = -0.68). In contrast, mean PA pressure
      was not significantly correlated with apnea index or with sleep desaturation.
      These data indicate that daytime PH was not directly related to sleep-disordered
      breathing, but was related to daytime hypoxemia, daytime hypercapnia, obesity,
      obstructive and restrictive respiratory impairments, and secondary polycythemia.

PMID- 8544379
TI  - [Pulmonary hypertrophic osteoarthropathy and clubbing of fingers in patients with
      lung cancer].
AB  - We examined clinical characteristics of patients with primary lung cancer
      associated with clubbing of the fingers or pulmonary hypertrophic
      osteoarthropathy. Clubbing was observed in 12.5% of patients with lung cancer.
      Squamous cell carcinoma was frequently associated with clubbing. Clubbing was
      found in all clinical stages. PaO2 and PaCO2 were normal in patients with lung
      cancer, which suggests that neither hypoxemia nor hypercapnia caused the clubbing
      in these patients. Pulmonary hypertrophic osteoarthropathy was found in three
      patients with lung cancer (two men and one woman, mean age 49 years). The
      incidence was 2.9% among lung cancer patients with clubbing, 0.22% in all lung
      cancer patients, and was apparently lower than those in reports from outside
      Japan. One of these patients has stage IIIA squamous cell carcinoma, one had
      stage IV large cell carcinoma, and one had stage IV adenocarcinoma. In all cases
      bone scans were useful for diagnosis and for following the clinical course.

PMID- 8544380
TI  - [Home days ratio in patients treated with long-term oxygen therapy].
AB  - The home days ratio (days at home/observation period) is an important index for
      evaluating the efficacy of therapy for chronic disease. To compute the home days
      ratio in patients treated with long-term oxygen therapy, we retrospectively
      studied the records of 72 consecutive patients with chronic respiratory failure
      who received long-term oxygen therapy from the Department of Pulmonary Medicine,
      Ogaki Municipal Hospital. These patients were representative of those treated
      with long-term oxygen therapy in terms of age, cause of hypoxemia, blood gas
      values, and pulmonary function. The home days ratio gradually decreased; it was
      92.7 +/- 15.2% during the first year, 87.5 +/- 24.0% during the second year, and
      78.5 +/- 39.7% during the third year. The home days ratios in survivors (n = 39)
      were greater than in non-survivors (n = 33). For the first year: 96.7 +/- 7.5%
      vs. 85.8 +/- 21.9%, p = 0.034; for the second year: 99.0 +/- 2.6% vs. 71.4 +/-
      31.0%, p = 0.004; for the third year: 96.0 +/- 9.0% vs. 48.4 +/- 53.1%, p =
      0.081, for survivors and non-survivors, respectively. These data suggest that non
      survivors can be distinguished from survivors soon after the start of oxygen
      therapy.

PMID- 8544381
TI  - [Role of cyclooxygenase metabolites in the increase in pulmonary vascular
      permeability caused by mechanically activated white blood cells].
AB  - To study the role of cyclooxygenase metabolites in changes in the pulmonary
      vasculature induced by mechanically activated white blood cells (WBCs), the
      effects of activated and inactive WBCs, and of a cyclooxygenase inhibitor, were
      studied in isolated perfused lungs from Sprague-Dawley rats. WBCs were activated
      by gentle agitation in a glass container for 10s. Baseline measurements were
      made, and then activated or inactive WBCs were added to the perfusate. Perfusion
      was stopped for 90 minutes, and then started again. The effects of the
      cyclooxygenase inhibitor meclofenamate on the pulmonary vascular filtration
      coefficient and on pulmonary vascular resistance were also measured. In the group
      that received activated WBCs, the pulmonary vascular filtration coefficient and
      the pulmonary vascular resistance were about 2.5 times and 3.3 times higher,
      respectively, than those in the group that received inactive WBCs. However, this
      apparent increase in the filtration coefficient caused by activated WBCs was
      partly blocked by meclofenamate. Histological examination indicated that
      meclofenamate did not prevent the adhesion of WBCs to the pulmonary vascular
      endothelium. These date indicate that WBCs that have been made to adhere to
      vessel walls can induce pulmonary vascular injury via cyclooxygenase products.

PMID- 8544382
TI  - [Development of infection with Aspergillus flavus in woman being treated for
      allergic pulmonary Aspergillosis caused by Aspergillus fumigatus].
AB  - A 36-year-old woman who raised plants in a large greenhouse came to our hospital
      because of a cough and purulent sputum. A chest X-ray film showed infiltrative
      shadows in the left middle lung field. Aspergillus fumigatus was isolated from
      samples of sputum and bronchoalveolar lavage fluid obtained from the left B5.
      Biopsy specimens revealed hyphae elements of aspergillus species and eosinophils
      in a plug of viscous material. Also, eosinophils and lymphocytes had infiltrated
      through bronchial epithelium without aspergillus species. She was given a
      diagnosis of allergic aspergillosis caused by Aspergillus fumigatus. Fluconazole
      was given and her symptoms and infiltrative shadows improved. Seventy days after
      treatment with fluconazole began, her symptoms recurred along with an abnormal
      shadow in the left upper lung field on a chest x-ray film. Aspergillus flavus,
      but not Aspergillus fumigatus, was isolated from samples of sputum and
      bronchoalveolar lavage fluid obtained from the left lung (S1+2). Biopsy specimens
      of the lung showed eosinophilic pneumonia. She was treated with itraconazole and
      her symptoms and abnormal radiographic shadows disappeared. She had no asthmatic
      attack or central bronchiectasis du ring the illness. This was a case of allergic
      pulmonary aspergillosis without asthmatic symptoms. It is interesting that one
      species of aspergillus was replaced by another during treatment.

PMID- 8544383
TI  - [Chronic Beryllium disease after exposure to low-beryllium-content copper].
AB  - A 24-year-old man was admitted to our hospital because of exertional dyspnea and
      abnormal shadows on chest X-ray film. He worked in a factory, where he was
      exposed to 1.8% beryllium-copper alloys. His job was to draw out heated beryllium
      copper wire to make it more fine. Chest X-ray film and chest CT scan showed left
      sided pneumothorax, diffuse fine reticulonodular shadows, and several cysts.
      Pulmonary-function tests showed a restrictive disorder and a low diffusing
      capacity. A specimen obtained by open-lung biopsy showed epithelioid cell
      granuloma and alveolitis, which were compatible with chronic beryllium disease.
      The beryllium content of the lung tissue was 0.045 microgram/gram. Beryllium
      lymphocyte transformation tests on blood and on bronchoalveolar lavage fluid were
      positive. Based on these findings, chronic beryllium disease was diagnosed. After
      treatment with 1 mg/kg of prednisolone daily, dyspnea disappeared. Then the dose
      was tapered slowly. In Japan, chronic beryllium disease is extremely rare, and to
      our knowledge only 22 other cases have been reported.

PMID- 8544384
TI  - [Cardiac sarcoidosis with myopathy and advanced A-V nodal block in a woman with a
      previous diagnosis of sarcoidosis].
AB  - In 1992, a 49-year-old woman was admitted to the hospital because of exertional
      dyspnea. Three years earlier sarcoidosis had been diagnosed, and the patient was
      found to have bilateral hilar lymphadenopathy. The eye, skin, and knee joint were
      also involved. During the second hospital stay, atrial flutter with advanced A-V
      nodal block, scattered defects on a 201T1 scintigram, and marked cardiomegaly on
      chest roentgenogram led to the diagnosis of cardiac sarcoidosis. Signs and
      symptoms of cardiac failure subsided after placement of an artificial cardiac
      pacemaker, but the patient still complained of mild muscle weakness in the lower
      extremities on exertion. 67Ga scintigraphy revealed marked accumulation in the
      lower extremities, and muscle biopsy of the left gastrocnemius revealed numerous
      epithelioid cell granulomas with muscle fiber degeneration. Oral corticosteroid
      therapy was effective. A review of the 24 cases of sarcoid myopathy reported in
      Japan indicated that the male-to-female ratio is 1:3.8. As compared to patients
      in whom myopathy led to the diagnosis of sarcoidosis, those in whom myopathy
      developed after sarcoidosis was diagnosed were (1) relatively older, (2) more
      likely to have multiple organ involvement, and (3) more likely to have cardiac
      sarcoidosis. Corticosteroids were beneficial in about three quarters of these 16
      cases, who received corticosteroid therapy.

PMID- 8544385
TI  - [Pulmonary non-Hodgkin's lymphoma that arose in mucosa-associated lymphoid tissue
      of the salivary gland and was diagnosed at autopsy].
AB  - A 70-year-old woman complained of a dry mouth and swelling in the area of the
      left parotid gland for 6 years, and was admitted for evaluation of an abnormal
      shadow on chest X-ray film. She underwent a lip biopsy and a 99mTcO4- scintigram
      of the salivary gland, and Sjogren's syndrome was diagnosed. Histopathological
      examination of the percutaneous lung biopsy specimen showed pseudolymphoma, and
      examination of a specimen of the left parotid gland tumor showed myoepithelial
      sialadenitis. The patient died of respiratory failure due to a right pleural
      effusion 4 years later. Autopsy revealed pulmonary non-Hodgkin's lymphoma
      (diffuse, large, B cell, IgG) with monotonous infiltration of centrocyte-like
      cells. A retrospectively resected specimen of the left parotid gland tumor showed
      non-Hodgkin's lymphoma similar to that found in the autopsied lung. This patient
      probably had pulmonary non-Hodgkin's lymphoma that arose in mucosa-associated
      lymphoid tissue of the salivary gland and was associated with Sjogren's syndrome.

PMID- 8544386
TI  - [Improvement of pulmonary eosinophilic granuloma after smoking cessation in two
      patients].
AB  - We encountered two cases in which pulmonary eosinophilic granuloma improved after
      cessation of smoking. The patient in case 1 was a 39-year-old woman. She smoked
      10-15 cigarettes a day for 20 years. The patient in case 2 was a 19-year-old man.
      He smoked a pack of cigarettes a day for 5 years. CT revealed cystic lesions and
      small nodular lesions predominantly in the upper and middle lung fields.
      Diagnosis was made by thoracoscopic lung biopsy in case 1 and by transbronchial
      lung biopsy in case 2. After smoking cessation, symptoms, CT findings, and vital
      capacity of both patients improved remarkably. Smoking cessation may have been
      related to the improvement in these patients.

PMID- 8544387
TI  - [Leukoencephalopathy in a patient being treated for small cell lung cancer].
AB  - A 62-year-old man was given a diagnosis of small cell lung cancer, and received 6
      courses of combination chemotherapy (PE therapy) composed of cisplatin (80 mg/m2,
      day 1) and etoposide (100 mg/m2, days 1, 2, 3). Multiple brain metastases were
      found, and whole brain irradiation (44 Gy) was given. Eleven months after
      radiotherapy, he suffered from dizziness and abnormal gait. Enhanced CT of the
      head showed slight enlargement of the lateral ventricles and markedly low density
      of the white matter, but no evidence of intracranial tumor involvement. A
      magnetic resonance scan (axial T2-weighted) showed symmetric extensive
      hyperintensity in the white matter. Treatment-related leukoencephalopathy caused
      by the PE therapy and whole brain irradiation was diagnosed. He was alive 8
      months after the appearance of neurological symptoms, without recurrence of lung
      cancer. A search of the literature revealed no previous report of
      leukoencephalopathy related to PE therapy.

PMID- 8544388
TI  - [An advanced invasive thymoma that responded remarkably to neoadjuvant
      chemotherapy with carboplatin, adriamycin, and etoposide].
AB  - A 23-year-old man was admitted to the hospital with hoarseness caused by
      recurrent nerve palsy. The chest X-ray film and CT scan on admission showed a
      large mass in the antero-superior part of the mediastinum and a small round
      mediastinal mass adjacent to right inferior pericardium. Examination of a
      specimen aspirated from the mediastinal mass revealed thymoma. The tumor was
      considered to be inoperable because of the pericardial dissemination, and the
      patient was treated with carboplatin, Adriamycin, and etoposide. After 4 courses
      of chemotherapy, remarkable regression of both tumors was observed on a chest X
      ray film. The patient underwent surgery, and no remaining tumor was found. A
      combination of carboplatin, Adriamycin, and etoposide may be useful as
      neoadjuvant chemotherapy for advanced invasive thymoma.

PMID- 8544389
TI  - [Chronic necrotizing pulmonary aspergillosis treated with itraconazole and
      inhaled amphotericin B].
AB  - A 52-year-old man with chronic necrotizing pulmonary aspergillosis complicated by
      a residual tuberculous cavity was admitted to the hospital because of fever and a
      new infiltration shadow in the right lower lobe. Aspergillus was isolated
      repeatedly from his sputum, though he had been treated with itraconazol for 9
      months. Combination therapy with itraconazol (200 mg) and inhaled amphotericin B
      (AMPC, 10 mg, 4 times a day) was begun. The infiltration shadow gradually
      resolved. The concentration of AMPC in serum was measured by high-performance
      liquid chromatography, and was found to be 0.09 micrograms/ml, which is equal to
      the AMPC concentration obtained with daily oral administration of 2400 mg. This
      case shows that, contrary to previous opinion, AMPC can be effectively
      administered by inhalation. We know of no previous reports of similar cases. In
      addition, itraconazol and inhaled AMPC may have had a synergistic effect in this
      case.

PMID- 8544390
TI  - [A bronchial carcinoid tumor in a patient with a high level of serum
      carcinoembryonic antigen].
AB  - A 76-year-old man was admitted to our hospital with a cough and bloody sputum.
      The level of serum carcinoembryonic antigen (CEA) was high (528.6 ng/ml), and the
      chest X-ray film revealed a large mass shadow in the lower left lung field.
      Bronchoscopic examination revealed complete obstruction of the left basal
      bronchus by a polypoid tumor coated with a white necrotic substance. Histologic
      examination of a specimen of the tumor led to the diagnosis of carcinoid. Left
      lower lobectomy and S5 segmentectomy were done. The operative diagnosis was also
      histologically carcinoid tumor. Immunohistochemical staining for CEA showed
      strong reactivity in tumor cells. The serum CEA level was normal when measured 2
      months after the operation. Therefore, the excess serum CEA measured before the
      operation was probably secreted by tumor cells.

PMID- 8544391
TI  - [Primary pulmonary amyloidosis with multiple nodules].
AB  - A 42-year-old man complained of a productive cough and exertional dyspnea.
      Roentgenogram and computed tomography of the chest showed several nodular
      shadows, and an open lung biopsy was done. Congo-red staining and electron
      microscopy showed the pulmonary nodules to be amyloid with infiltration by plasma
      cells and foreign body giant cells. The amyloid was identified as AL-lambda and
      kappa type by immunohistochemical examination, and plasma cells and foreign body
      giant cells contained light chains. In situ hybridization studies showed intens
      signals of lambda mRNA and kappa mRNA in the plasma cells, but no signal in the
      foreign body giant cells. The foreign body giant cells appeared to have
      phogocytosed the light chains. Electron microscopic examination showed an
      "amyloid star" in the foreign body giant cells. Morphologically, this observation
      showed that the amyloid was produced by the foreign body giant cells.

PMID- 8544392
TI  - [Liver herniation simulating a benign lung tumor].
AB  - A 49-year-old woman complained of coughing and sputum production a mass shadow
      was seen in the right lower lung field on a chest radiography. The shadow was
      first suspected to represent a benign lung tumor, because of its clear margin and
      narrow pedicle. After detailed examination liver herniation was suspected, since
      the CT number of the tumor was similar to that of the liver. Liver herniation was
      finally confirmed by chest MRI, liver scintigraphy and angiography of the
      abdomen. Liver herniation should be differentiated from an intrathoracic mass in
      the right lower lung field.

PMID- 8544393
TI  - Pathophysiology of renal tubular obstruction: therapeutic role of synthetic RGD
      peptides in acute renal failure.

PMID- 8544394
TI  - Chronic regulation of the proximal tubular Na/H antiporter: from HCO3 to SRC.

PMID- 8544395
TI  - Beta 2 microglobulin isoforms in healthy individuals and in amyloid deposits.
AB  - beta 2 microglobulin (beta 2m) is classically known to have isoforms with
      isoelectric points (pI) 5.7 and 5.3. New isoforms of beta 2m with lower pI,
      probably due to modifications with advanced glycation end products, were found in
      the amyloid deposits of dialysis related amyloidosis (DRA), and they were
      proposed as the amyloidogenic forms of beta 2m. The other modifications in beta
      2m from amyloid deposits are partial proteolysis and single amino acid
      replacement (Asn by ASp at position 17). However, there are no data on the
      sequence of the different isoforms of beta 2 m from amyloid deposits. Amyloid
      deposits surgically obtained from the carpal tunnel from 13 dialysis treated
      patients and urine from 10 healthy volunteers and 5 living-related kidney donors
      were analyzed for beta 2m content. Two-dimensional gel electrophoresis (2D-PAGE)
      of beta 2m from amyloid deposits showed the presence of four or more isoforms
      with pIs < 5.7. All the spots migrating at 12 kDa Mr region and between 4 and 6
      pH reacted with rabbit anti-human beta 2m antibody by Western blotting,
      confirming that they were beta 2m isoforms. beta 2m isoforms from the amyloid
      deposits were then separately purified with an IEF column (PB94, Pharmacia) for
      analysis. Enough quantities of three pure beta 2m isoforms could be obtained in
      two cases. The sequence analysis showed an intact N-terminus in all the isoforms.
      There was Asn in the 17th residue in all the isoforms sequenced. 2D-PAGE of urine
      from 8 out of the 10 healthy volunteers showed the presence of beta 2m. In two of
      them beta 2m also displayed four different isoforms. At least four isoforms were
      observed in urine of all the kidney donors. The present study shows that the
      elution peaks of three different beta 2m isoforms in gel isoelectrofocusing
      contain beta 2m with intact N-terminus. None of them have deamidated their 17th
      residue. More importantly, the beta 2m isoforms with lower pI are not specific
      for amyloidosis as they were found in urine from kidney donors and in normal
      volunteers. These results bring into question the hypothesis that dialysis
      related amyloidosis is due to the known modifications on beta 2m. They suggest
      that the precipitation of beta 2m into amyloid fibrils should result from the
      interaction of beta 2m with other factors with amyloid enhancing activity.

PMID- 8544396
TI  - Nitric oxide antagonizes the actions of angiotensin II to enhance
      tubuloglomerular feedback responsiveness.
AB  - The present study was designed to investigate whether nitric oxide (NO)
      antagonizes angiotensin II (Ang II) in modulating the tubuloglomerular feedback
      (TGF) system. Maximum TGF responses were assessed by evaluating stop-flow
      pressure (SFP) responses to late proximal perfusion with artificial tubular fluid
      (40 nl/min). Peritubular capillary (PTC) infusion of 10(-3) M NG-L-arginine (NLA)
      at a rate of 20 nl/min, and infusion of 10(-7) and 10(-6) M Ang II at rates that
      did not decrease SFP under conditions of zero flow to the macula densa (resting
      SFP), augmented maximum SFP feedback responses to 12.0 +/- 1.7, 12.1 +/- 2.4 and
      16.9 +/- 3.0 mm Hg, respectively (all P < 0.01 vs. control response). Combined
      PTC infusion of NLA and 10(-7) M Ang II at a rate of 20 nl/min resulted in
      decreases in resting SFP in 7 of the 12 nephrons studied. When the infusion rate
      was decreased to 15 +/- 3 nl/min, concomitant PTC infusion of NLA and 10(-7) M
      Ang II was associated with a tremendous increase in maximum TGF responses (23.8
      +/- 3.9 mm Hg; P < 0.01 vs. responses during PTC NLA or Ang II) in the absence of
      a decrease in resting SFP. During AT1 receptor blockade using losartan, SFP
      feedback responses were attenuated to 1.6 +/- 0.6 mm Hg and PTC infusion of NLA
      only augmented TGF responses to 3.8 +/- 1.0 mm Hg. These results strongly suggest
      that local NO antagonizes Ang II with respect to the regulation of TGF
      responsiveness. Disruption of this balance by NO synthesis inhibition strongly
      potentiates TGF-independent and TGF-dependent actions of Ang II on the
      preglomerular vasculature.

PMID- 8544397
TI  - Alpha 1B-adrenergic receptors in rat renal microvessels.
AB  - Although several alpha-adrenergic receptor genes are expressed in the rat kidney,
      their expression in the renal vasculature has not been studied. Since
      pharmacological studies have suggested that an alpha 1B-adrenergic receptor may
      mediate renal vasoconstriction, we studied the expression of alpha 1B-adrenergic
      receptors in renal microvessels, from 10- to 14-week-old male spontaneously
      hypertensive rats (SHR) and their normotensive control, the Wistar-Kyoto rat
      (WKY). In these microvessels, isolated by perfusion with iron, alpha 1B
      adrenergic receptor mRNA levels (by ribonuclease protection assay) were similar
      in SHR and WKY rats. Photo-affinity labeling with [125I]-arylazidoprazosin
      demonstrated the presence of alpha 1B-adrenergic receptor protein. Maximum
      receptor density (determined by 3H-prazosin binding: Bmax 59.8 +/- 4.1 and 58.7
      +/- 4.3; Kd 0.48 +/- 0.05 nM and 0.31 +/- 0.06 nM in SHR and WKY, respectively)
      and chloroethylclonidine (CEC)-sensitive binding sites (determined by [125I]-(2
      beta(4-hydroxyphenyl)-ethylaminomethyl)-tetralone binding) (125I-HEAT) were
      similar in SHR and WKY rats. There are two novel findings in these studies: (1)
      the alpha 1B-adrenergic receptor gene is expressed in renal microvessels of WKY
      and SHR; (2) alpha 1B-adrenergic receptor gene expression in renal microvessels
      is not altered in adult SHR. The failure to down-regulate expression of the alpha
      1B-adrenergic receptor at the mRNA and protein level in the SHR could result in
      persistence of alpha 1B-adrenergic receptor effects and contribute to the
      increased vascular resistance in hypertension.

PMID- 8544398
TI  - Effect of acid/base balance on H-ATPase 31 kD subunit mRNA levels in collecting
      duct cells.
AB  - The cortical collecting duct (CCD) adapts to disturbances of acid/base balance by
      adjusting the direction and magnitude of its HCO3 transport. The molecular events
      involved in this adaptation are incompletely understood, but it seems that
      adaptation is accompanied by changes in the activity and intracellular
      distribution of the vacuolar H-ATPase. The goal of this study was to examine the
      effects of metabolic acidosis and alkali load on the expression of the mRNA
      encoding the 31 kD subunit of the vacuolar H-ATPase in rabbit CCD cells. Pairs of
      rabbits received either a NH4Cl load or a NaHCO3 load for 16 hours, resulting in
      a urinary pH of 5.53 +/- 0.38 and 8.42 +/- 0.10, respectively. CCD cells were
      isolated by immunodissection and mRNA levels of the H-ATPase 31 kD subunit and of
      beta-actin were determined from the same cDNA samples by quantitative RT-PCR. H
      ATPase mRNA levels were significantly higher in CCD cells from acidotic than
      alkali-loaded rabbits (2.51 +/- 1.3 vs. 0.65 +/- 0.2; P < 0.05). Similar
      differences in the H-ATPase 31 kD subunit mRNA levels were observed by Northern
      blotting. beta-actin mRNA levels were comparable in CCD cells of the two groups.
      The distribution of the H-ATPase 31 kD subunit mRNA was determined among the
      three cell types of the CCD, that is in alpha- and beta-intercalated cells (alpha
      ICC and beta-ICC) and principal cells (PC) isolated by fluorescence-activated
      cell sorting. The level of expression was comparable in alpha-ICCs and beta-ICCs,
      whereas PCs contained very low levels of H-ATPase mRNA. In both alpha-ICC and
      beta-ICC the levels of the 31 kD H-ATPase mRNA were significantly higher in
      acidotic than in alkali-loaded rabbits. These results indicate that in the rabbit
      CCD changes in acid/base balance not only regulate the subcellular distribution
      of the vacuolar H-ATPase but also alter its expression, at least at the mRNA
      level.

PMID- 8544399
TI  - Stimulation of calcium transport by amiloride in mouse distal convoluted tubule
      cells.
AB  - This study examined the mechanism by which amiloride dissociates Na and Ca
      transport in distal convoluted tubules. Control rates of Na uptake averaged 288
      nmol/(min mg protein) and were inhibited 39% by microM amiloride. Amiloride had
      no effect on Cl uptake. Resting membrane voltage, measured with the voltage
      sensitive dye DiOC6 (3), averaged -70 mV. Amiloride hyperpolarized cells in a
      reversible manner by 18 mV. Control rates of Ca uptake averaged 2.8 nmol/(min mg
      protein) and increased by 39% in the presence of amiloride. Alterations of
      intracellular Ca activity were measured in single cells loaded with Fura2-AM.
      Control intracellular Ca activity averaged 100 nM. Amiloride increased
      intracellular Ca activity in a concentration-dependent manner to a maximum of 330
      nM at microM amiloride. Amiloride analogues ethylisopropyl amiloride (EIPA) and
      dimethylbenzamil (DMB), which preferentially block Na/H and Na/Ca exchange,
      respectively, had no effect on Na or Ca influx or on intracellular Ca activity.
      The dihydropyridine Ca channel blocker nifedipine inhibited amiloride-stimulated
      Ca uptake and the rise of intracellular Ca activity but had no effect on membrane
      voltage. It is concluded that amiloride blocks Na entry mediated by Na channels.
      Inhibition of Na entry results in membrane hyperpolarization, which activates Ca
      entry by dihydropyridine-sensitive Ca channels.

PMID- 8544400
TI  - Long-term treatment of rats with FGF-2 results in focal segmental
      glomerulosclerosis.
AB  - Long-term treatment (8 and 13 weeks) of rats with FGF-2 led to albuminuria and to
      increase in serum creatinine indicating the development of chronic renal failure.
      Histologically, the classic picture of focal segmental glomerulosclerosis (FSGS)
      was found; males were more severely affected than females. Among the early
      changes podocyte lesions were most prominent. Surprisingly, mitotic figures in
      podocytes and a considerable fraction of bi(multi)nucleated podocyte profiles
      were found in treated animals (roughly 16% in males, 8% in females). Since an
      increase of cell number of podocytes was not evident, we conclude that FGF-2
      stimulates podocytes to re-enter the cell cycle and to undergo mitosis (nuclear
      division). However, podocytes-probably due to their highly differentiated cell
      shape in the adult-are unable to complete cell division (cytokinesis) resulting
      in bi- or multinucleated cells; in others cell division may fail totally leading
      to podocyte degeneration. Most podocytes in FGF-2-treated rats exhibited
      degenerative changes including cell body attenuation, extensive pseudocyst
      formation, widespread foot process effacement, as well as detachments from the
      glomerular basement membrane (GBM). The development of FSGS in this model is very
      uniform. In the case of podocyte detachments from peripheral capillaries,
      parietal cells become attached to naked GBM-areas, establishing the nidus for
      development of a tuft adhesion to Bowman's capsule. Tuft adhesions grow by
      encroaching of parietal cells onto adjacent capillary loops, resulting eventually
      in a solid synechia with collapsed capillaries, that is, what represents
      segmental sclerosis. The distribution of adhesions on the inner surface of
      Bowman's capsule appeared to be random, including all locations between the
      vascular and urinary pole. The two main aspects of this study (inability of
      podocytes to replicate and development of FSGS based on progressing podocyte
      degeneration) may be part of a vicious cycle. FGF-2 stimulates podocytes to enter
      cell division thereby conveying them into a hazardous situation. If a podocyte
      fails and degenerates it cannot be replaced, aggravating the situation for the
      remaining cells and possibly increasing their predisposition to respond to
      mitogenic stimuli. Similar mechanisms may constitute the development of FSGS in
      other experimental as well as human glomerulopathies.

PMID- 8544401
TI  - DNA synthesis is dissociated from the immediate-early gene response in the post
      ischemic kidney.
AB  - The response of the kidney to ischemic injury includes increased DNA synthesis,
      which is preceded by rapid and brief expression of the c-fos proto-oncogene.
      While the timing of these two events would suggest that c-Fos participates in an
      immediate-early gene program leading to proliferation, no direct test of this
      hypothesis exists. The purpose of these studies was (1) to determine whether c
      fos is expressed as part of a typical immediate-early (IE) gene response, which
      would require co-expression of c-jun and sensitivity to cycloheximide, and (2) to
      determine whether the cells expressing c-Fos are the same as those undergoing DNA
      synthesis. Northern analysis was performed on renal mRNA at different times
      following release of a 50 minute period of renal hilar clamping. c-jun and c-fos
      mRNA were rapidly and briefly expressed following renal ischemia and their
      expression was superinduced by cycloheximide in a manner typical of an immediate
      early gene response. 3H-thymidine autoradiography performed on semi-thin sections
      from intravascularly perfusion fixed kidneys 24 hours following induction of
      ischemia showed labeled nuclei in cells lining the damaged proximal tubules of
      the outer stripe of the outer medulla, as well as proximal tubules in the cortex
      and interstitial cells throughout the kidney. However, immunohistochemical
      localization of c-Fos and c-Jun protein occurred predominantly in nuclei of the
      thick ascending limb, distal tubule and collecting duct cells. The studies
      demonstrate that c-fos and c-jun are expressed following renal ischemia as a
      typical immediate-early gene response, but they are expressed in cells that do
      not enter the cell cycle. The failure of the cells to enter the cell cycle may
      depend on the co-expression of jun-B and jun-D, which suppress the mitogenic
      activity of c-Jun in other cells. The data suggest that the IE response following
      renal ischemia is part of the stress response, which is antiproliferative rather
      than proliferative. The role of the stress response during renal ischemia and the
      fate of the cells undergoing it are unknown.

PMID- 8544402
TI  - Induction of plasminogen activator inhibitor type 1 in murine lupus-like
      glomerulonephritis.
AB  - Three major components of the plasminogen activators (PA)/plasmin system are
      synthesized physiologically in glomeruli, and can be involved in glomerular
      proteolysis and extracellular matrix metabolism: tissue-type PA (tPA), urokinase
      (uPA) and PA inhibitor type 1 (PAI-1). To explore the possible role of a
      dysregulation of the plasmin protease system in the development and progression
      of lupus-like glomerulonephritis, we studied the expression of the renal plasmin
      protease components during the course of the disease, either acute, induced by
      IgG3 monoclonal cryoglobulins, or chronic, occurring spontaneously in three
      different lupus-prone mice: (NZBxNZW)F1, BXSB and MRL-lpr/lpr. RNase protection
      assays and in situ hybridizations revealed a marked glomerular induction of PAI-1
      mRNA abundance without any significant changes in renal tPA and uPA mRNA levels
      in the two different types of lupus-like glomerulonephritis. The overexpression
      of PAI-1 mRNA occurred in parallel with a significant decrease in glomerular tPA
      catalyzed enzymatic activity as determined by zymographic analysis. In addition,
      a concomitant increase in glomerular expression of transforming growth factor
      beta 1 (TGF-beta 1) mRNA was observed. The demonstration of a close correlation
      between the PAI-1 and TGF-beta 1 mRNA levels and the severity of lupus-like
      glomerular lesions suggests that a pertubation of the glomerular PA/PAI balance,
      resulting from a marked TGF-beta 1-mediated induction of PAI-1 gene expression,
      plays an important role in the progression of lupus-like glomerular lesions,
      leading to glomerulosclerosis.

PMID- 8544403
TI  - Monocyte cell-surface CD14 expression and soluble CD14 antigen in hemodialysis:
      evidence for chronic exposure to LPS.
AB  - Expression of CD14 on peripheral blood monocytes and serum levels of the 53 kD
      soluble CD14 antigen were investigated in patients with end-stage renal failure
      who were undergoing chronic hemodialysis (HD) with either cuprophane/hemophane
      (CU/HE) low-flux (LF) or polysulfone/polyamide (PS/PA) high-flux (HF) membranes.
      Baseline expression of CD14 was significantly lower in HD patients compared to
      uremic patients and normal controls. Patients using PS/PA membranes disclosed a
      further decreased CD14 expression than patients with CU/HE membranes. Specific
      fluorescence intensity for CD14 increased 15 minutes after the start of the
      dialysis session and was on average 22% higher after hemodialysis. The serum
      levels of sCD14 were elevated about 2.5-fold in HD patients compared to healthy
      controls (5.4 +/- 1.3 vs. 2.2 +/- 0.5 mg/liter, P < 0.0001) and were
      significantly higher compared to non-dialyzed patients with chronic renal failure
      (3.9 +/- 1.0 mg/liter, P < 0.001). After regular dialysis with high-flux
      membranes, soluble CD14 serum concentrations significantly increased (P < 0.001)
      compared to pre-dialysis levels. Values of soluble CD8 (54 kD) were elevated only
      1.5-fold in HD patients relative to healthy controls, whereas serum levels of the
      low molecular weight soluble CD23 (20 kD) 12 and 19-fold in patients treated with
      HF-HD and LF-HD, reflecting the renal impairment and filtration through HF
      membranes. Thus, high sCD14 values in HD patients may stem from increased release
      of the up-regulated membrane antigen due to monocyte activation during
      hemodialysis treatment. Since the CD14 antigen is involved in LPS-induced
      monocyte activation, the influence of lipopolysaccharide on CD14 expression and
      sCD14 release was investigated in vitro. Addition of 1 ng/ml or 0.01 ng/ml LPS to
      whole blood significantly enhanced monocyte CD14 expression after 30 or 60
      minutes of incubation. The release of soluble CD14 by cultured peripheral blood
      monocytes significantly increased in the presence of 0.01 ng/ml LPS during a five
      day incubation experiment. Our results demonstrate an enhanced expression of CD14
      by monocytes after HD and increased sCD14 serum levels possibly due to chronic
      exposure to trace amounts of endotoxins, as supported by in vitro experiments.

PMID- 8544404
TI  - Production and cytokine-mediated regulation of monocyte chemoattractant protein-1
      by human proximal tubular epithelial cells.
AB  - Impairment of renal function in various types of glomerular disease is associated
      with tubulointerstitial changes. The mechanism of mononuclear cell infiltration
      in the interstitium is not fully understood. Recently, monocyte chemoattractant
      protein-1 (MCP-1) has been identified as a monocyte-specific chemotactic factor.
      We analyzed the presence of MCP-1 in renal biopsies from patients with various
      forms of glomerular disease and demonstrated that MCP-1 expression is increased
      in renal tubular epithelial cells during disease. Further analysis showed that
      various cell lines of human proximal tubular epithelial cells (PTEC) produce MCP
      1 in culture under serum-free conditions and that the production is inhibited by
      cycloheximide. IL-1 alpha and TNF-alpha enhanced the production by each cell line
      in a dose- and time-dependent manner as measured by radioimmunoassay. Northern
      blot analysis demonstrated that IL-1 alpha and TNF-alpha markedly enhanced the
      expression of MCP-1 mRNA. Taken together these observations support the notion
      that MCP-1 is synthesized de novo by PTEC. MCP-1 produced by PTEC is found to be
      13 kD by gel filtration chromatography. It is chemotactically active for
      monocytes. We conclude that in various types of glomerular disease, MCP-1
      expression in tubular epithelial cells is associated with up-regulation of MCP-1
      production by PTEC. These findings raise the possibility that macrophages may
      accumulate in renal interstitium as a consequence of MCP-1 production by PTEC.

PMID- 8544405
TI  - Cyclosporine enhances the expression of TGF-beta in the juxtaglomerular cells of
      the rat kidney.
AB  - The mediators of cyclosporine (CsA) nephrotoxicity remain ill defined. In this
      study, we describe evidence of increased amounts of transforming growth factor
      beta (TGF-beta) in the kidneys of adult male Wistar rats treated with CsA (5 to
      25 mg/kg/day) for four weeks. Localization of TGF-beta was undertaken
      immunocytochemically at both light and electron microscope levels and Northern
      blot analysis was applied to detect changes in transcription of TGF-beta. In
      control rats, weak to moderate immunostaining for TGF-beta was observed, in the
      juxtaglomerular arterioles. CsA treatment resulted in a dose-dependent increase
      in the number of stained afferent and interlobular arterioles and in the
      intensity of staining. The number of stained afferent arterioles increased from a
      control value of 0.21 +/- 0.08/mm2 cortex to 0.84 +/- 0.15/mm2 cortex, P < 0.01,
      and to 1.12 +/- 0.10/mm2 cortex, P < 0.01, in rats treated with CsA 12.5
      mg/kg/day and 25 mg/kg/day, respectively. The number of interlobular arterioles
      stained for TGF-beta increased from a control value of 0.07 +/- 0.05/mm2 to 0.31
      +/- 0.02/mm2, P < 0.05, and 0.39 +/- 0.07/mm2, P < 0.01, in rats treated with
      CsA, 12.5 mg/kg/day and 25 mg/kg/day, respectively. At the electron microscope
      level, TGF-beta was localized exclusively within the granular cells of the
      juxtaglomerular arterioles. Northern blot analysis suggested that this enhanced
      staining is due to increased transcription of TGF-beta 1. We have therefore
      observed an association between TGF-beta and CsA-induced nephrotoxicity. While
      this does not establish a causal link, it leads us to postulate that TGF-beta,
      alone or in combination with other growth factors, may play a role in the
      pathogenesis of CsA induced nephrotoxicity.

PMID- 8544406
TI  - Cloning, tissue distribution, and intrarenal localization of ClC chloride
      channels in human kidney.
AB  - Two kidney-specific chloride channels, ClC-K1 and ClC-K2, have been isolated from
      rat kidney. In the present study, we sought to isolate human homologue of rat ClC
      K2 chloride channel that was present in the thick ascending limb of Henle's loop
      and collecting ducts. Human kidney cDNA library was screened with the whole rat
      ClC-K2 cDNA probe. Two highly homologous but not identical cDNAs were isolated
      and sequenced. Northern analysis showed that both clones were expressed only in
      kidney among various human tissues, demonstrating that kidney-specific ClC family
      members were also present in human kidney. Because both clones had almost the
      same nucleotide identity (approximately 80%) with rat ClC-K2, we could not
      determine by sequence alone which human clone corresponded to rat ClC-K2.
      Accordingly, we performed reverse transcription PCR using dissected human nephron
      segments and identified the site of expression of each clone in human nephron
      segments. One clone was only expressed in the thin limb of Henle's loop and the
      other was expressed in glomeruli, proximal tubules, and collecting ducts. We
      identified the latter clone as human ClC-K2 based on the localization of rat ClC
      K1 and ClC-K2. Identification of human ClC-K2 clone will be of help in
      understanding the genetic involvement of chloride channel in disorders of
      chloride transport such as Bartter's syndrome.

PMID- 8544407
TI  - Intragraft expression of IL-10 messenger RNA: a novel correlate of renal
      allograft rejection.
AB  - A major conceptual advance is the formulation that type I cytokines (such as IL-2
      and IFN-gamma) enhance cellular immunity and are host-protective, and that type
      II cytokines (such as IL-4 and IL-10) dampen cellular immunity and facilitate the
      progression of infection. We have explored the intragraft expression of type I
      and type II cytokines during human renal allograft rejection. RNA was isolated
      from 98 allograft biopsies, and reverse transcription-PCR was used to amplify and
      identify intragraft expression of mRNA encoding IL-2, IFN-gamma, IL-4, or IL-10.
      Intragraft expression of IL-7 mRNA and TGF-beta 1 mRNA was also investigated. Our
      investigation demonstrated that: (a) intragraft expression of IL-10 mRNA and IL-2
      mRNA are significant correlates of acute rejection; (b) IL-4, IL-7, IFN-gamma and
      TGF-beta 1 mRNA expression do not correlate with acute rejection; and (c) IL-10
      does not prevent in vivo expression of IFN-gamma, IL-2, IL-7, or TGF-beta 1. Our
      studies identify, for the first time, a significant association between
      intragraft IL-10 mRNA expression and acute rejection, and suggest that treatment
      strategies capable of constraining IL-10 expression might be of value in the
      prevention of acute rejection.

PMID- 8544408
TI  - Heparin-induced endothelial cell cytoskeletal reorganization: a potential
      mechanism for vascular relaxation.
AB  - We have previously shown that heparin given subcutaneously on a daily basis
      lowers blood pressure in hypertensive rat models, and that this blood pressure
      lowering effect is endothelium-dependent. The present study describes the effects
      of heparin on endothelial cell (EC) apical surface structures and cytoskeletal
      elements, namely, actin and vimentin as well as EC proliferative activity. The EC
      line (CRL 1998) was cultured, treated with different concentrations of heparin
      (0, 50, 100, 500 U/ml) for 4, 24 or 48 hours, and fixed for scanning electron
      microscopy (SEM), and immunofluorescence microscopy (IFM) studies. Enzyme-linked
      immunosorbent assays (ELISA) and flow cytometric analysis were performed on EC
      monolayers treated with different concentrations of heparin for quantitative
      detection of actin and vimentin. By SEM study the cell surface showed generalized
      smoothing as a result of blunting of surface microvilli with increasing time of
      exposure and dosage of heparin. By IFM study, the detectable actin signal within
      ECs became progressively reduced in both its cellular distribution and the
      apparent number of cells that remained reactive. By 48 hr/500 U heparin, the
      actin signal was almost undetectable. Vimentin showed a moderate reduction in the
      cellular distribution of labeling. Quantitatively, actin was significantly
      reduced after the 24 hour treatment with a higher dose of heparin (500 U/ml),
      from a baseline optical density (OD) of 1.12 +/- 0.060 to 0.866 +/- 0.008 (P <
      0.0027). After 48 hours of treatment at both 100 U/ml and 500 U/ml heparin, actin
      was significantly reduced from a baseline OD of 1.347 +/- 0.063 to 1.090 +/-
      0.039 (P < 0.0039) and 0.844 +/- 0.074 (P < 0.008), respectively. However,
      vimentin was significantly reduced only after 48 hours of treatment with a high
      dose of heparin (500 U/ml), from baseline OD 1.82 +/- 0.052 to 1.41 +/- 0.004 (P
      < 0.002). The flow cytometric findings were virtually identical to the ELISA data
      for actin and vimentin. These qualitative and quantitative changes in actin and
      vimentin are consistent with apparent smoothing and relaxation of the EC's apical
      surface. Labeling with the cell cycle marker MIB-1 (monoclonal antibody Ki-67),
      showed a progressive reduction in the observed intensity in heparin treated cells
      with substantially fewer cells being positive. After a 48 hour treatment with
      heparin (500 U/ml), most ECs displayed only dim labeling of the nucleolus. This
      finding is consistent with an antiproliferative effect. Overall, these findings
      are additive to our previous observations, and demonstrate that heparin causes EC
      cytoskeletal reorganization which is a potential mechanism for vascular
      relaxation.

PMID- 8544409
TI  - Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor
      and IGF-binding protein-2 mRNA and peptide levels in normal and nephrectomized
      rat kidney.
AB  - Immunocytochemistry, in situ hybridization, and radioimmunoassay were employed to
      examine the cellular distribution of mRNAs and proteins for IGF-I, II, IGF-II/M6P
      receptor, IGFBP2 as well as the levels of IGF-I and II in normal and unilaterally
      nephrectomized (Nx) adult rat kidneys. A similar distribution of immunoreactive
      IGF-I, and -II as well as IGF-II/M6P receptor was found in the principal cells of
      the cortical collecting duct and in all cells of the inner medullary collecting
      duct. In addition, immunostainable IGF-I and IGF-II/M6P receptor were noted in
      some inner medullary loops of Henle, while IGFBP2 was seen in the collecting
      ducts and loops of Henle of the inner medullar and the renal vasculature of all
      animals. By comparison, in situ hybridization revealed IGF-I mRNA only in the
      medullary thick ascending limbs while IGF-II mRNA was localized to the wall of
      the renal microvasculature in all kidneys. IGFBP2 mRNA was localized to the renal
      corpuscle and to inner medullary interstitial cells of all kidneys. These data
      suggest that renal IGF-I and IGFBP2 are synthesized at upstream sites along the
      nephron and then transported downstream for interaction with IGF receptors.
      Following nephrectomy, the renal levels of IGF-I peptide and mRNA were elevated
      at both 5 and 33 days post-nephrectomy, supporting a potential functional role
      for IGF-I in stimulating the structural and functional recovery in compensatory
      hypertrophy.

PMID- 8544410
TI  - PDGF and TGF-beta contribute to the natural course of human IgA
      glomerulonephritis.
AB  - PDGF and TGF-beta are known mediators of mesangial cell proliferation and matrix
      expansion. The presence of these regulatory factors was examined in 30 renal
      biopsies from patients with IgA glomerulonephritis (IgA-GN) at the mRNA and
      protein level. Normal renal tissue served as control. The mRNA expression of PDGF
      A/B chains, PDGF-beta R and TGF-beta 1 was evaluated by means of RT/PCR with
      subsequent Southern blot hybridization and/or non-radioactive in situ
      hybridization. In addition, PDGF-AB/BB, PDGF-beta R, TGF-beta isoforms (beta 1,
      beta 1 + 2, beta 2 + 3), the small TGF-beta 1 latency associated peptide (TGF
      beta 1 LAP) and the extracellular matrix proteins tenascin and decorin were
      analyzed by immunocytochemistry. The expression of growth factors was correlated
      with light microscopic and clinical features. Compared to normal control kidneys,
      an increased expression of PDGF-BB/PDGF-beta R mRNAs and the corresponding
      proteins was observed in all biopsies with IgA-GN. Up-regulation was related to
      the degree of glomerular proliferation and the extent of fibrosing interstitial
      lesions. In contrast, there was a discordance between TGF-beta 1 mRNA and protein
      expression (evaluated by immunocytochemistry). In all biopsies, irrespective of
      the stage of the disease, abundant TGF-beta 1 transcripts were detected, whereas
      TGF-beta 1 immunoreactivity was expressed to a lesser degree and disclosed a more
      variable staining pattern. In patients with significant proliferative glomerular
      lesions and minor tubulointerstitial alterations, TGF-beta 1 positivity was
      confined to areas of glomerular proliferation, whereas in cases with more severe
      histology including sclerosing lesions TGF-beta 1 immunoreactivity was less
      prominent. The distribution and the intensity of TGF-beta 1 LAP staining commonly
      exceeded the positivity noted for TGF-beta 1, indicating only limited TGF-beta 1
      activation. A decreased reactivity for tenascin accompanied the morphological
      features of glomerular sclerosis. The staining patterns and the fact that only
      very few inflammatory cells, particularly CD68 positive monocytes/macrophages,
      were detected in glomeruli confirm that predominantly resident glomerular cells
      (mesangial and endothelial cells) are the major source of up-regulated growth
      factor production in IgA-GN. Since the expression of PDGF-AB/BB paralleled the
      severity of proliferative glomerular changes, PDGF seems to represent a potential
      indicator of activity in this condition. It is suggested that an imbalance
      between PDGF and TGF-beta (by restricted translation and/or activation)
      production contribute to the progressive nature of IgA-GN.

PMID- 8544411
TI  - Insights into the biochemical mechanism of maleic acid-induced Fanconi syndrome.
AB  - Maleic acid administration is known to produce the Fanconi syndrome, although the
      biochemical mechanism is incompletely understood. In this study the effect of a
      single injection of maleic acid (50 mg/kg body wt, i.v.) on the rat renal ATPases
      was examined. Maleic acid rapidly caused bicarbonaturia, natriuresis, and
      kaliuresis. When nephron segments were microdissected, there was an 81 +/- 2%
      reduction in proximal convoluted tubule (PCT) Na-K-ATPase activity (P < 0.005)
      and a 48 +/- 4% reduction in PCT H-ATPase activity (P < 0.01). Enzyme activity
      (Na-K-ATPase, H-ATPase, H-K-ATPase) in the medullary thick ascending limb of
      Henle's loop and distal nephron segments was normal. In vitro, maleic acid (1 and
      10 mM) inhibited Na-K-ATPase in PCT, but it had no effect on H-ATPase in PCT.
      Prior phosphate infusion to maleic acid-treated rats attenuated urinary
      bicarbonate wastage by 50% (P < 0.05); activity of proximal tubule Na-K-ATPase
      and H-ATPase activities were partially protected as compared to the animals given
      maleic acid alone (P < 0.05). Renal cortical ATP levels were not altered at the
      concentration of maleic acid used in this study (that is, 50 mg/kg body wt), but
      higher doses of maleic acid (that is, 500 and 1000 mg/kg body wt) caused ATP
      levels to fall. Maleic acid did not affect cortical medullary total phosphate
      concentration, however, P32 turnover (1 and 24 hr) was altered by prior phosphate
      infusion. A protective effect of prior phosphate loading on the membrane bound Pi
      pool (insoluble) was seen while the cytosolic Pi pool (soluble) was not different
      from control. Thus, maleic acid-induced "Fanconi" syndrome likely results from
      both direct inhibition of proximal tubule Na-K-ATPase activity and membrane-bound
      phosphorus depletion. The former mechanism would reduce activity of the sodium
      dependent transporters (that is, Na/H antiporter), while the latter would inhibit
      the electrogenic proton pump (H-ATPase). The combination of reduced proximal
      tubule Na-H exchange and H-ATPase activities would markedly inhibit bicarbonate
      reabsorption and result in the metabolic acidosis universally seen in the Fanconi
      syndrome.

PMID- 8544412
TI  - Erythrocyte transmembrane flux and renal clearance of oxalate in idiopathic
      calcium nephrolithiasis.
AB  - An anomaly in erythrocyte oxalate transport has been reported in patients with
      idiopathic calcium oxalate nephrolithiasis. Even if clinical and experimental
      evidence suggests a causal role of this cellular anomaly in calcium
      nephrolithiasis, a definitive answer to this fundamental question is still
      lacking. We approached this problem by searching for a possible relationship
      between the erythrocyte oxalate self-exchange anomaly and the renal clearance of
      this anion in stone formers. In 10 idiopathic calcium-oxalate renal stone
      formers, and 10 healthy subjects we evaluated the erythrocyte oxalate flux rate,
      and the renal fractional clearance of oxalate by a recently described enzymathic
      procedures for plasma oxalate determination. With respect to controls, stone
      formers had higher oxalate flux rate in erythrocytes, and higher oxalate renal
      fractional clearance with a significant direct correlation between the two
      parameters. These data are compatible with a membrane transport abnormality
      within the kidney of these stone formers, and the existence of a common defect of
      the oxalate transport shared by both erythrocytes and tubular renal cells. The
      latter may be crucial in the pathogenesis of calcium oxalate nephrolithiasis, by
      modifying the renal handling of oxalate.

PMID- 8544413
TI  - Calcium-regulated parathyroid hormone release in patients with mild or advanced
      secondary hyperparathyroidism.
AB  - Differences in the regulation of parathyroid hormone (PTH) release by calcium are
      thought to account for excess PTH secretion in patients with secondary
      hyperparathyroidism (2 degrees HPTH). To determine whether calcium-regulated PTH
      release varies with the severity of 2 degrees HPTH in patients with end-stage
      renal disease, dynamic tests of parathyroid gland function were done using the
      four-parameter model in 26 patients with 2 degrees HPTH documented by bone
      biopsy. Estimates of the set point did not differ among patients categorized as
      mild (basal serum PTH < 400 pg/ml), moderate (basal PTH 400 to 600 pg/ml) or
      severe (basal PTH > 600 pg/ml) 2 degrees HPTH; values were 1.23 +/- 0.06
      mmol/liter, 1.24 +/- 0.06 mmol/liter and 1.23 +/- 0.05 mmol/liter, respectively,
      and none of these set point estimates differed from results obtained in normal
      volunteers, 1.21 +/- 0.02 mmol/liter (NS). The slope of the sigmoidal ionized
      calcium-PTH curve also did not differ among groups. Set point values did not
      correspond to basal serum PTH levels, to the maximum serum PTH level observed
      during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia
      in patients with 2 degrees HPTH. In contrast, basal serum PTH values were
      positively correlated with both the maximum serum PTH level observed during
      hypocalcemia (r = 0.76, P < 0.01), and the minimum serum PTH level attained
      during calcium infusions (r = 0.78, P < 0.01). Calcium-regulated PTH release does
      not differ with the degree of 2 degrees HPTH, and set point abnormalities do not
      account for excess PTH secretion in patients with chronic renal failure as judged
      by in vivo dynamic tests of parathyroid gland function. The results suggest that
      variations in parathyroid gland size are the major contributor to excessive PTH
      secretion in patients with chronic renal failure.

PMID- 8544414
TI  - Diurnal variation in glomerular charge selectivity, urinary albumin excretion and
      blood pressure in insulin-dependent diabetic patients.
AB  - The urinary albumin excretion rate (AER) in a subgroup of patients with insulin
      dependent diabetes mellitus (IDDM) steadily increases. In these patients a
      concomitant reduction of the glomerular charge selectivity index (SI) has been
      demonstrated. The aim of the present study was to evaluate whether diurnal
      variation in AER could be related to a diurnal variation in SI and/or a diurnal
      blood pressure variation. Thirty-three patients with IDDM, 27 with normal albumin
      excretion (AER < 20 micrograms/min; group D(o)) and six with incipient
      nephropathy (AER from 20 to 200 micrograms/min; group DA), were studied. AER and
      SI (renal clearance ratio of total-IgG/IgG4) were measured in three different
      urine collecting periods: period A (8:00 a.m. to 12:00 a.m.), period B (12:00
      a.m. to bedtime) and period C (bedtime to 8:00 a.m.). A significant increase in
      SI was seen during the nighttime: period A, 1.6 (0.2 to 3.8; mean, range); period
      B, 1.7 (0.3 to 3.0); and period C, 2.0 (0.2 to 4.0); P = 0.01. Corresponding to
      this observation, an overall significant decrease in AER was found: period A, 10
      (3 to 137) micrograms/min (median, range); period B, 8 (3 to 84) micrograms/min;
      and period C, 5 (0 to 78) micrograms/min; P < 0.001. In all three sampling
      periods a negative correlation was found between AER and SI. When group D(o) was
      analyzed alone, the results were similar. Diurnal variation in blood pressure was
      significantly positively correlated with AER in group DA, but was not correlated
      to variation in AER in D(o). We suggest that in normoalbuminuric IDDM patients
      diurnal variation in AER is related to diurnal variation in SI.

PMID- 8544415
TI  - Hemofiltration in human sepsis: evidence for elimination of immunomodulatory
      substances.
AB  - Continuous hemofiltration is widely used for renal replacement therapy in
      patients with acute renal failure. It has been suggested that hemofiltration may
      also eliminate toxic mediators thought to be important in the pathophysiology of
      sepsis. The present study examined whether hemofiltration can activate or
      eliminate inflammatory mediators in patients with sepsis, and whether
      ultrafiltrate can alter specific functions of peripheral blood mononuclear
      leukocytes (PBMC) in vitro. Veno-venous hemofiltration was performed in 16
      patients and in 5 healthy volunteers. Pre-filter (afferent), post-filter
      (efferent) and ultrafiltrate concentrations of cytokines (IL-1 beta, IL-6, IL-8,
      TNF alpha) and of complement components (C3, C3adesArg, C5adesArg, terminal
      complement complex) were measured after the beginning of hemofiltration (t0), and
      60 minutes later (t60). PBMC, and monocyte and lymphocyte subfractions were
      incubated with ultrafiltrate, and cytokines were determined in the supernatants.
      Hemofiltration did not induce significant mediator activation. There was no
      evidence for significant cytokine elimination. However, pre-filter C3adesArg
      concentration showed a significant decline during hemofiltration (patients: t0 =
      676.9 +/- 99.7 ng/ml, t60 = 545.4 +/- 83.2, P < 0.001; volunteers: t0 = 54.8 +/-
      13.3 ng/ml, t60 = 33.9 +/- 10.7, P < 0.001). Ultrafiltrate from septic patients
      significantly stimulated PBMC and monocyte TNF alpha release, but suppressed
      lymphocyte IL-2 and IL-6 production. Ultrafiltrate from volunteers was without
      effect. Hemofiltration effectively eliminates certain mediators such as
      C3adesArg. Ultrafiltrate contains compounds with significant immunomodulatory
      qualities. Therefore, hemofiltration may represent a new modality for removal of
      immunomodulatory mediators.

PMID- 8544416
TI  - Low molecular weight proteinuria in Chinese herbs nephropathy.
AB  - Urinary excretion of five low molecular weight proteins (LMWP) [beta 2
      microglobulin (beta 2m), cystatin C (cyst C), Clara cell protein (CC16), retinol
      binding protein (RBP) and alpha 1-microglobulin (alpha 1m)], albumin and N-acetyl
      beta-D-glucosaminidase (NAG) were quantified in 16 patients who followed a weight
      reduction program which included Chinese herbs, which have been incriminated in
      the genesis of Chinese herbs nephropathy (CHN). An additional group of four
      patients transplanted for CHN were investigated. Urinary data were obtained for
      comparison purpose in five groups of proteinuric patients: two groups with normal
      serum creatinine (SCr) and glomerular albuminura [12 patients with diabetes
      mellitus and microalbuminuria (DN), 10 patients with primary nephrotic syndrome
      (NS)]; two groups with normal SCr and toxic nephropathy [6 patients with
      analgesic (AN), 9 patients with cadmium nephropathy (CdN)]; and one group of
      seven patients with glomerular diseases and increased SCr (GN). Patients were
      classified according to serum level S beta 2m to take into account the
      possibility of overflow proteinuria at S beta 2m > or = 5 mg/liter. Three
      patients (CHN0) with a S beta 2m < 5 mg/liter, had a normal urinary protein
      pattern including NAG and a normal S beta 2m. Eight patients (CHN1) with a S beta
      2m < 5 mg/liter had various abnormalities of their urinary protein pattern. In
      four of them (CHN1a) only beta 2m, RBP and CC16 were increased while total
      proteinuria and SCr were normal. In the other four (CHN1b and c) albumin, cyst C,
      alpha 1m and NAG were also elevated, while total proteinuria and SCr were
      moderately raised. Five patients (CHN2) with a S beta 2m > or = 5 mg/liter had a
      markedly increased excretion of all LMWP, albumin and NAG (CHN1 vs. CHN2, P <
      0.05) as well as a further increase in total proteinuria and SCr. The urinary
      LMWP/albumin concentration ratio was strikingly higher in CHN patients than in
      patients with glomerular albuminuria (CHN1 vs. DN and NS, P < 0.01) or moderate
      renal failure with elevated S beta 2m level (CHN2 vs. GN, P < 0.01), confirming
      the existence of a tubular proteinuria independent of glomerular albuminuria or
      overflow proteinuria. A similar proteinuria pattern was present in the two toxic
      nephropathies (CdN and AN). This pattern was no longer recognizable after
      transplantation. In conclusion, CHN exhibits various profiles of tubular
      proteinuria which are the hallmarks of the disease. This pattern is still
      detectable in patients with renal failure and/or glomerular albuminuria. It is
      identical to that observed in cadmium and analgesic nephropathies. It does not
      recur after transplantation. Its most sensitive and reliable marker is a raised
      urinary level of CC16 or RBP.

PMID- 8544417
TI  - Role of thromboxane A2 and prostacyclin in uninephrectomy-induced attenuation of
      ischemic renal injury.
AB  - Contralateral uninephrectomy attenuates unilateral renal ischemic injury. The
      present work was performed to elucidate whether the beneficial effect of
      uninephrectomy was mediated through the modification of the actions of
      thromboxane A2 (TxA2) or prostacyclin. Unilateral ischemic injury was provoked by
      a 60-minute left renal artery occlusion in right nephrectomized (Nx) and in sham
      nephrectomized (Sham-Nx) rats. Inulin clearance (CIn) of left kidney 48 hours
      after ischemia was significantly higher in the Nx group than in the Sham-Nx group
      (0.11 +/- 0.07 vs. 0.00 +/- 0.00 ml/min/kidney, P < 0.05). Ischemia-induced
      tubular necrosis was also less in Nx animals. Proliferating cell nuclear antigen
      (PCNA) staining, a marker for cell proliferation, was found more markedly in Nx
      rats than in Sham-Nx animals. Forty-eight hours after ischemia, renal cortical
      TxB2 content was greater in Sham-Nx rats than in Nx rats (29.5 +/- 4.4 vs. 18.3
      +/- 1.7 pg/mg protein, P < 0.05). No significant difference was found in the
      intrarenal content of 6-keto prostaglandin F1 alpha between two ischemia groups.
      A thromboxane synthetase inhibitor, OKY-046 (100 mg/kg/day, i.p.), significantly
      increased CIn 48 hours after ischemia (0.00 +/- 0.00 vs. 0.17 +/- 0.09
      ml/min/kidney, P < 0.05) and attenuated ischemic tubular damage in Sham-Nx rats
      but not in Nx animals. Under OKY-046 treatment, no significant difference was
      found in postischemic CIn and ischemic tubular damage between the Nx and Sham-Nx
      groups. OKY-046 also increased PCNA expression in the cortex and outer stripe in
      Sham-Nx animals. These data suggest that less production of intrarenal TxB2 plays
      an important role for the uninephrectomy-induced attenuation of ischemic renal
      damage and for the facilitation of tubular recovery.

PMID- 8544418
TI  - Ischemia increases neutrophil retention and worsens acute renal failure: role of
      oxygen metabolites and ICAM 1.
AB  - The role of neutrophils in acute renal failure (ARF) is controversial. Although
      ARF occurs in neutropenic subjects, we found that ischemic kidneys activated
      neutrophils to cause ARF in isolated perfused rat kidneys. To further define the
      interaction between neutrophils and renal ischemia, we performed quantitative
      assessment of neutrophil accumulation during renal ischemia. Non-ischemic and
      ischemic rat kidneys were perfused by the isolated kidney technique with
      unstimulated, primed, or fully activated, indium-labeled neutrophils. Neutrophil
      accumulation was quantitated by measuring indium retention after 60 minutes of
      perfusion. In non-ischemic kidneys, only activated neutrophils were retained
      while after 20 minutes of renal ischemia, unstimulated as well as primed
      neutrophils were retained. Following 10 minutes of ischemia, primed neutrophils
      (but not unstimulated neutrophils) were retained. In the presence of neutrophil
      retention, there were decreases in GFR and tubular sodium reabsorption. To
      determine the role of ICAM 1 in ischemic injury, rats were treated with anti-ICAM
      1 prior to ischemia and ischemic kidneys were reperfused with unstimulated
      neutrophils and anti-ICAM 1. After ischemia, the neutrophil component of
      reperfusion injury in isolated kidneys was prevented with anti-ICAM 1. Oxygen
      metabolites have been shown to induce EC expression of ICAM 1. To determine the
      role of ICAM 1 in oxidant-mediated renal injury, ischemic isolated kidneys were
      reperfused with catalase (CAT) and non-ischemic kidneys were perfused with
      hydrogen peroxide. Following ischemia, reperfusion with CAT prevented neutrophil
      retention and injury. In non-ischemic kidneys, hydrogen peroxide caused primed
      neutrophil retention, activation and renal injury which were completely prevented
      with anti-ICAM 1. IN CONCLUSION: (1) Ischemic kidneys cause neutrophil retention,
      activation, and worsening of renal injury in isolated kidneys; and 2) neutrophil
      retention is dependent on the state of neutrophil activation, duration of renal
      ischemia and is mediated by oxygen metabolites and ICAM 1. This synergism could
      account for the high frequency of ARF in conditions such as sepsis where there is
      both renal hypoperfusion and neutrophil priming.

PMID- 8544419
TI  - Inferior outcome of two-haplotype matched renal transplants in blacks: role of
      early rejection.
AB  - Acute rejection in the early post-transplant period is a major determinant of
      long-term outcome. A cohort analysis was performed to evaluate the race-specific
      incidence rates of early acute rejection episodes (AR) and delayed graft function
      (DGF) in Americans of African (blacks) and European (whites) descent (N = 2565)
      who received a 2-HM living-related donor (LRD) first kidney transplant between
      1984 and 1992. After adjusting for center and recipient characteristics, blacks
      had a higher incidence of AR during the initial transplant hospitalization
      (blacks 13.2% vs. whites 7.4%, OR = 1.64, P = 0.02). DGF also occurred more
      frequently in blacks (unadjusted OR = 1.58, P = 0.07). Blacks with AR had
      significantly worse Cox-adjusted five year graft survival than similarly affected
      whites (blacks 50% vs. whites 76%, P < 0.01). We conclude that failure to take
      immunosuppressive medications cannot be implicated as a cause of the higher
      incidence of AR during the initial transplant hospitalization in black kidney
      transplant recipients. The excess risk of AR in blacks may reflect previously
      reported intrinsic differences in immune responsiveness and/or pharmacokinetics
      of immunosuppressive agents. The profound deleterious effect of AR appears to be
      largely responsible for the accelerated rate of late graft loss in African
      Americans.

PMID- 8544420
TI  - A 10-year follow-up of a randomized study with methylprednisolone and
      chlorambucil in membranous nephropathy.
AB  - The natural course of idiopathic membranous nephropathy is variable, with some
      patients slowly progressing to renal failure while others maintain normal renal
      function over the entire time. Whether to treat this disease or not is
      controversial due to the lack of controlled data about the long-term effects of
      treatment. We updated at 10 years the results of a controlled trial in which 81
      patients with idiopathic membraneous nephropathy and nephrotic syndrome were
      randomly assigned to receive symptomatic therapy (39 patients) or a treatment of
      six months with methylprednisolone and chlorambucil (42 patients). The
      probability of surviving without developing end-stage renal disease at 10 years
      was 92% in patients given methylprednisolone and chlorambucil versus 60% in
      controls (P = 0.0038). The slope of the reciprocal of plasma creatinine up to 10
      years was significantly better in treated patients than in controls (P = 0.035).
      The probability of having a complete or partial remission of the nephrotic
      syndrome was significantly higher in treated patients (P = 0.000). Patients
      assigned to therapy spent significantly longer time without nephrotic syndrome
      than untreated patients (P = 0.0001). Four patients had to stop treatment because
      of reversible side-effects. In the long-term one treated patient developed
      diabetes and another one became obese. In conclusion, a six-month therapy with
      methylprednisolone and chlorambucil increases the probability of remission of
      proteinuria and protects from renal function deterioration even in the long-term.
      This treatment may avoid dialysis or death within 10 years to about one third of
      nephrotic patients with membranous nephropathy.

PMID- 8544421
TI  - Factors determining hemoglobin carbamylation in renal failure.
AB  - Carbamylated hemoglobin (carhb) is formed by the reaction of hemoglobin with
      cyanate, a product of in vivo urea dissociation. It is found in high levels in
      patients with renal failure and may be useful in their clinical evaluation.
      Accordingly, we measured carhb by HPLC after acid hydrolysis in 73 patients with
      renal failure and 11 controls. Mean carhb levels (expressed as micrograms valine
      hydantoin/g Hb), were highest in chronic renal failure (CRF, 146 +/- 13),
      intermediate in end-stage renal disease on hemodialysis (ESRD, 106 +/- 7), and
      lowest in acute renal failure (ARF, 80 +/- 12) when compared to normal subjects
      (27 +/- 2). In all patients carhb was significantly correlated with BUN but not
      with creatinine, bicarbonate, or phosphate. For any level of BUN above 80 mg/dl,
      carhb was substantially higher in CRF than in ARF. Predialysis BUN and urea
      reduction ratio (URR) were significant predictors of carhb in ESRD. To
      investigate the effect of time of exposure and BUN level on the rate of
      carbamylation of hemoglobin, blood from normal subjects and dialysis patients was
      incubated in vitro with urea equivalent to BUN levels of 50, 100, 150, and 200
      mg/dl and assayed for carhb at 0, 5, 9, and 14 days. Carhb increased linearly
      over the first nine days of urea exposure and leveled off thereafter. The rate of
      carbamylation increased as BUN increased and was significantly higher in
      hemoglobin from dialysis patients than from normal subjects. These results show
      that the higher the level of carhb at baseline, the higher the rate of
      carbamylation upon exposure to increasing urea concentrations. We conclude that
      carhb formation is dependent on urea concentration and length of exposure to
      urea. The rate of carhb formation for a given urea concentration is greater in
      hemoglobin already carbamylated, and this may explain why carhb is higher in CRF
      than in ARF at BUN levels greater than 80 mg/dl. Carhb may thus be a useful index
      of the duration and degree of exposure to high blood urea levels in patients with
      renal failure, and may potentially serve as an index of the adequacy of dialysis.

PMID- 8544422
TI  - Assessment of renal resistance index after captopril test by Doppler in essential
      and renovascular hypertension.
AB  - Ultrasonic duplex scanning has been validated as a noninvasive method to evaluate
      the kidney arteries and hemodynamic characteristics of renal blood flow in
      patients with renal artery stenosis. The purpose of our study was to assess the
      changes in renal vascular impedance in 22 patients with renovascular
      hypertension, as compared with 45 essential hypertensives and 15 normotensives,
      by using the Doppler parameter resistance index (RI) before and after a captopril
      oral test. After the captopril test the delta RI decreased significantly in the
      stenotic artery (P < 0.05). Univariate analysis showed that PRA values after
      captopril correlated inversely with the changes of RI only in the stenotic artery
      (P < 0.05). Thus, our findings suggest that the application of the captopril test
      to renal echo-Doppler may represent a feasible, noninvasive, and inexpensively
      useful tool in the screening studies aimed at diagnosing renovascular
      hypertension.

PMID- 8544423
TI  - Drug-induced changes in renal hippurate clearance as a measure of renal blood
      flow.
AB  - We studied the accuracy of the plasma 131I-hippurate clearance technique to
      monitor drug-induced changes in renal blood flow (RBF) by comparing it to a flow
      probe technique in six conscious, chronically instrumented dogs. Placebo caused
      no change in RBF, either established by hippurate clearance (ERPFhip) or by renal
      blood flow probe (RBFprobe). Enalaprilate induced a rise in ERPFhip and RBFprobe
      (+26 +/- 5 and 44 +/- 12%), as did dopamine (+16 +/- 4 and +33 +/- 5%).
      Intravenous infusion of norepinephrine induced a rise in ERPFhip (+2 +/- 6%, NS)
      and in RBFprobe (+18 +/- 3%), as did nitroprusside (+14 +/- 4% and +13 +/- 6%,
      NS). Indomethacin induced a fall in ERPFhip (-8 +/- 2%) and in RBFprobe (-7 +/-
      3%, NS), as did angiotensin II (-19 +/- 1 and -26 +/- 3%). Renal hippurate
      extraction (Ehip) was affected by enalaprilate, dopamine, and angiotensin II (-5
      +/- 2, -7 +/- 1, and +5 +/- 2%, respectively). Hematocrit (Hct) was affected by
      dopamine, norepinephrine, and nitroprusside (+2 +/- 1, +6 +/- 1, and -6 +/- 2%,
      respectively). Drug-induced changes in ERPFhip correlated well with changes in
      RBFprobe (r = 0.902, P < 0.01). Changes in Ehip did not independently affect this
      relation, whereas changes in Hct did: delta RBF(% of baseline) = 1.529 x delta
      ERPFhip(% of baseline) + 1.296 x delta Hct(% of baseline). These data indicate
      that drug-induced changes in plasma hippurate clearance can, even when changes in
      renal hippurate extraction are unknown, be used as a reliable indicator of
      changes in renal blood flow if changes in hematocrit are taken into account.

PMID- 8544424
TI  - Iron, heme oxygenase, and glutathione: effects on myohemoglobinuric proximal
      tubular injury.
AB  - This study assessed the impacts of iron, heme oxygenase (HO), hydroxyl radical
      (.OH), and glutathione (GSH) on the initiation phase of myohemoglobinuric
      proximal tubular injury using a novel model system. Rhabdomyolysis was induced in
      rats by glycerol injection and four hours later proximal tubular segments (PTS)
      were isolated. They were incubated for 0 to 90 minutes either in the presence or
      absence of an iron chelator (deferoxamine; DFO), .OH scavengers, an .OH trapping
      agent (salicylate; to gauge .OH production), GSH, or catalase. In selected
      experiments, an HO inhibitor (Sn protoporphyrin) was given at the time of
      glycerol injection to assess HO's acute effects on the evolving injury. Cell
      death and lipid peroxidation were quantified by % LDH release and malondialdehyde
      (MDA) generation, respectively. PTS from normal rats served as controls. Post
      glycerol PTS manifested progressive LDH release (47 +/- 2%) and 20-fold MDA
      increments during the incubations, whereas only 11 +/- 1% LDH release and no MDA
      generation was observed in the normal PTS. DFO completely prevented both
      parameters of glycerol-induced injury. HO inhibition exerted an acute protective
      effect, despite previous in vivo data suggesting that HO is a cytoprotectant.
      Neither .OH scavengers nor catalase mitigated post-glycerol injury, the latter
      correlating with reduced, not increased, .OH production. GSH slightly decreased
      LDH release while causing a paradoxical threefold MDA increment. The latter was
      iron dependent (blocked by DFO), was expressed in normal PTS, and it could be
      reproduced by equimolar cysteine. That GSH increased iron-dependent lipid
      peroxidation in a cell free system (exogenous phosphatidylcholine) indicated that
      GSH metabolism to cysteine was not a requirement for this reaction. IN
      CONCLUSION: (1) chelatable iron can fully account for heme protein-triggered
      proximal tubular injury; (2) HO contributes to this injury, presumably by causing
      iron release; (3) the heme-induced injury appears to be mediated by non-.OH
      oxidizing intermediates; (4) GSH can exert both anti- and pro-oxidant effects;
      and (5) i.m. glycerol injection, followed by proximal tubular isolation,
      represents a new and highly useful model for studying direct determinants of heme
      protein cytotoxicity.

PMID- 8544425
TI  - Organ culture of rat kidney: a model for angiotensin II receptor ontogenic
      studies.

PMID- 8544426
TI  - Hemodynamic consequences of Cimino fistulas studied with finger pressure
      measurements during fistula compression.

PMID- 8544427
TI  - Cloning of mouse c-ros renal cDNA, its role in development and relationship to
      extracellular matrix glycoproteins.
AB  - Renal organogenesis ensues following reciprocal interactions between the
      uninduced metanephric mesenchyme and the ureteric bud. Conceivably, the presence
      of ligands or growth factors on a given cell type, and expression of receptors,
      including receptor proto-oncogenes, on the other cell type of different lineage
      would facilitate such epithelial-mesenchymal interactions. During these
      interactions, other macromolecules, such as extracellular matrix (ECM) proteins,
      present at the epithelial-mesenchymal surface, also play a role in the kidney
      morphogenesis. In this study the proto-oncogene, c-ros, was cloned and sequenced;
      its role in the metanephric development was examined, and correlated with the
      changes in the expression of ECM proteins. The mouse c-ros renal cDNA, belonging
      to phosphotyrosine kinase (PTK) receptor family, had a translation product of
      2340 amino acids. The extracellular domain had 32 N-linked glycosylation sites
      and 30 cysteine residues. The transmembrane segment had a hydrophobicity
      approaching approximately 3.5. Multiple phosphorylation sites, typical of a PTK
      catalytic unit, were present in the cytoplasmic domain. The 3' noncoding region
      did not contain any A(U)nA mRNA instability motifs. The c-ros mRNA was highly
      expressed on the ureteric bud branches and their tips and on the developing
      glomeruli. Competitive RT-PCR analyses revealed the c-ros expression was the
      highest at 13th day of gestation, and it declined to very low levels during the
      neonatal period. Exposure of metanephric kidneys to c-ros antisense
      oligonucleotide, derived from the PTK domain, caused dysmorphogenesis of the
      kidney and loss of c-ros expression on the ureteric bud branches. Concomitant
      with the reduced c-ros gene expression, a decreased expression of ECM
      glycoproteins, in particular the proteoglycans, was observed. These findings
      suggest that the c-ros plays a role in the metanephric development, and its
      effects may be modulated by the ECM macromolecules present at the epithelial
      mesenchymal interface.

PMID- 8544428
TI  - Management of the diabetic transplant recipient.

PMID- 8544429
TI  - Treatment and prevention of hypertension: where have we been and where are we
      going?

PMID- 8544430
TI  - Limitations of therapeutic approaches to glomerular diseases.

PMID- 8544431
TI  - Acute renal failure: prevailing challenges and prospects for the future.
AB  - The increasing understanding of the molecular and cellular basis of acute renal
      failure and the development of cell culture methodology to grow differentiated
      cells in engineered structures provide substantial promise for new therapeutic
      derivatives to treat patients with acute renal failure (Table 3). The use of
      disintegrins to ameliorate intratubular obstruction, the administration of ANF to
      improve glomerular filtration, or the injection of growth factors to speed re
      epithelialization may prove effective in altering the natural history of this
      severe clinical disorder. Furthermore, the development of cell therapy with a
      renal tubule replacement device may add critical renal functional components not
      currently substituted with dialysis or hemofiltration. The potential therapeutic
      advances which may occur as we enter the next century to treat this devastating
      clinical disease process have substantial promise.

PMID- 8544432
TI  - End-stage renal disease: magnitude of the problem, prognosis of future trends and
      possible solutions.
AB  - The incidence rate per million population of treated end-stage renal disease
      (ESRD) has been increasing at similar rates in most countries that record counts
      of new ESRD patients per year. Data from the United States Renal Data System
      (USRDS) suggest an exponential growth for both incidence rates and prevalence
      rates. Doubling of the number of new patients per year occurred over a recent 8.5
      year period, and this interval was even shorter for older patients, Asians,
      Native Americans and for patients with diabetes or hypertension as cause of ESRD.
      Reasons for this growth in incidence include greater acceptance to therapy of
      older and sicker patients, reduced mortality from other conditions and possibly
      more kidney disease. A recent reduction in mortality rates for ESRD patients in
      the US has additionally influenced the growth in prevalence. In view of these
      striking recent trends a prognosis for the next decade is discussed. As major
      possible solutions prevention efforts for renal disease and for the progression
      of renal disease are proposed, as are means to enhance renal organ donation.

PMID- 8544433
TI  - Renal fibroblast heterogeneity.

PMID- 8544434
TI  - Dialysis: current status, contemporary limitations and future challenges.

PMID- 8544435
TI  - Long-term failure of renal transplants: adding insult to injury.
AB  - Although transplantation is the preferred choice for many end-stage renal disease
      patients, results are far from perfect and the demand for organs exceeds the
      available supply. After high initial success rates at one year, the subsequent
      course of randomly HLA matched cadaveric organs is an exponential loss of
      functioning grafts, with a half-life of seven to eight years. This process is one
      of progressive sclerosis and fibrosis which may result from the inability of
      available immunosuppressive agents to control a chronic type of rejection, or it
      may be the result of early immunological injury with progressive vascular injury
      occurring as a result of hemodynamically induced injuries, as seen in renal
      ablation animal models. Matching for HLA antigens has a major impact on this
      process, with half-lives of 20 years with HLA-A, HLA-B, HLA-DR matched cadaver
      donors. Various clinical risk factors, including the relative size of the donor
      kidney, ischemic injuries, and drug toxicities all predispose to a more rapid
      rate of chronic graft loss. These are likely to be additive to the damaging
      effects of rejection activity, with a final pathway of glomerulovascular
      sclerosis initiated when a critically low level of functioning nephrons is
      reached.

PMID- 8544436
TI  - Differences in the care of ESRD patients worldwide: required resources and future
      outlook.
AB  - RRT has crossed the threshold of clinical applications, and its value as an
      effective modality for management of ESRD is fully established. However, RRT has
      emphasized the wide gap between developed and developing countries. Most of the
      developed nations are able to provide sufficient funds, directly or indirectly,
      for RRT and have organized cadaver donor networks. However, providing RRT is
      particulary difficult in the developing countries where national incomes are not
      sufficient to cover even the basic requirements of their citizens. Although some
      developing countries are making active efforts to establish cadaver donor
      transplant programs, these are virtually nonexistent in the majority at this
      time. The abject poverty in the developing world and the increasing success rate
      of transplantation following the discovery of cyclosporine have led to the
      commercialization and sale of kidneys for transplantation, an unethical practice
      which must be curbed. There is a near unanimity of opinion that renal
      transplantation is far cheaper than prolonged dialysis, and the benefit to the
      recipient is enormous in terms of the years of life saved and the quality of
      life. Until such time as cadaveric donor programs become a reality in the
      developing countries, short periods of dialysis followed by transplants with
      living-related donor kidneys appear to be the most cost-effective treatments of
      ESRD.

PMID- 8544437
TI  - Reporting HIV infection in children: physician practices and perceptions.

PMID- 8544438
TI  - Measles control in institutional settings.
AB  - This paper reports on the utility of screening pediatric psychiatric admissions
      for the presence of antibodies to measles to determine the need for
      administration of MMR Vaccine to 314 children admitted over an 11-month period.
      Four fifths (80.6 percent) of the children had positive antibody tests when
      screened. No sex difference in antibody prevalence was noted but Caucasians were
      more likely (18.2 percent) than African American (6.2 percent) to have negative
      antibody tests. No relationship was noted between psychiatric diagnosis and
      antibody test results. A substantial proportion of adolescents have negative or
      equivocal measles antibody tests and interpretation of such results may be
      difficult. Antibody testing is cost-effective in institutional settings and, in
      the future, may become so in selected ambulatory settings.

PMID- 8544439
TI  - Backfire: AHCPR practice guideline for acute low back pain.
AB  - The AHCPR "Guideline for Acute Low Back Problems in Adults" is a must-read for
      every South Carolina physician treating low back pain. The 25-page pamphlet
      excels as a practical guide for swiftly triaging acute low back problems into the
      90 percent majority who recover within a month, from the few "red flag" and "red
      herring" serious back problems requiring urgent attention. But the Guideline
      panel overstepped its policymaking mandate by venturing into the quicksand of
      treatment by committee edict, rather than by on-the-spot caretakers. The rumbling
      backfire is that U. S. Government document, intended as practice guideline for
      routine acute back care, will come to haunt us as a practice standard for all
      back care. One-size-fits-all proposals for the majority short-change the few with
      more demanding healthcare resource requirements. Be sure to read the pamphlet;
      your patients, insurers, providers, administrators, journalists and attorneys
      will!

PMID- 8544440
TI  - Schamberg's disease: a case report.

PMID- 8544441
TI  - The stare that said it all.

PMID- 8544442
TI  - Join the fight against the flu!

PMID- 8544443
TI  - Feminist identities and preferred strategies for advancing women's positive self
      concept.
AB  - This study was an attempt to (a) determine the generalizability of the American
      based Feminist Identity Development Scale (FIDS; Bargad & Hyde, 1991) to female
      students in a New Zealand university and (b) examine the relationship between
      feminist identities (as measured by the FIDS) and preferred strategies for
      advancing women's self-concept. Female undergraduate university students (N =
      145) were given the FIDS and a self-concept strategy questionnaire. The factor
      structure of the FIDS was replicated for four of the five stages reported by
      Bargad and Hyde. Failure to replicate the remaining stage (revelation) was
      attributed to differences in the sample populations and the wording of the
      subscale. Positive correlations were found between the early stage of feminist
      identity development and individual-oriented self-concept strategies and also
      between the late stage of feminist identity development and group-oriented self
      concept strategies. These results suggest that as a woman's feminist identity
      develops, the strategies for advancing that self-concept change from individual-
      to group-oriented ones.

PMID- 8544444
TI  - Subtle prejudice against women in The Netherlands.
AB  - Subtle discrimination against women in the Netherlands was examined, using
      Dovidio and Gaertner's (1983) investigatory design and a sample of 56 male
      university sophomores. The following variables were manipulated: confederate's
      gender, confederate's role (supervisory vs. subordinate in relation to the
      participant), and confederate's cognitive ability (high vs. low). It was expected
      that a woman in a subordinate role would be offered help more often than a woman
      in a supervisory role would, and that a low-ability woman in a subordinate role
      would be offered help more often than a high-ability woman in the same role. The
      results supported these expectations even though there was no evidence of
      stereotyping in the written answers to the questionnaire.

PMID- 8544445
TI  - Open pelvic fracture: delayed diagnosis.

PMID- 8544446
TI  - A veteran with eosinophilia.

PMID- 8544447
TI  - An avoidable complication of septic arthritis.

PMID- 8544448
TI  - Child fatality review in Tennessee.

PMID- 8544449
TI  - Another pediatric nightmare.

PMID- 8544450
TI  - Acute renal failure associated with use of angiotensin converting enzyme
      inhibitor--a report of two children with Down's syndrome.

PMID- 8544451
TI  - Extrapulmonary tuberculosis in Tennessee: lessons from the last decade.
AB  - In conclusion, extrapulmonary TB remains a significant fraction of the total TB
      cases in Tennessee. During the last few years, the percentage of extrapulmonary
      TB in Tennessee has been on the increase. Understanding these changes in the
      epidemiology of extrapulmonary TB will help the clinician in making a prompt
      diagnosis, leading to appropriate therapy. Understanding the changing trends at
      the national level may aid state health departments in reorganizing disease
      control programs, thus, facilitating the eradication of TB and other communicable
      diseases in Tennessee.

PMID- 8544452
TI  - Comparison of pleuropneumonectomy and limited surgery for lung cancer with
      pleural dissemination.
AB  - The role of surgery in the management of lung cancer with pleural dissemination
      is controversial. We performed a retrospective analysis of our patients with lung
      cancer and pleural dissemination who were treated surgically. Between 1973 and
      1993, 1,206 patients with lung cancer underwent pulmonary resection at Kanazawa
      University Hospital. Among them, 40 (3.3%) had pleural dissemination without
      pleural effusion. The 1-, 3-, and 5-year survival rates for 38 patients (except 2
      patients undergoing exploratory thoracotomy alone) were 51.5%, 19.4%, and 19.4%,
      respectively. The 1-year survival rate in the 10 patients who underwent
      pleuropneumonectomy was only 20%, and 9 of these patients died within 18 months
      postoperatively (1 patient has survived for 25 months). In contrast, the 1-, 3-,
      and 5-year survival rates for the 14 patients who underwent resection of the
      primary tumor plus parietal pleurectomy were 85.1%, 35.5%, and 35.5%,
      respectively, a significantly better outcome (P < 0.01). Seven patients are still
      alive (the longest survival time is 65 months with the disease). The average
      survival time in the seven fatal cases was 18 months. In patients with lung
      cancer accompanied by pleural dissemination, it is quite possible that local
      excision plus pleurectomy will be justified.

PMID- 8544453
TI  - Lack of association between tumor necrosis and hsp-27 expression in primary
      breast cancer.
AB  - Overexpression of heat shock protein 27 (hsp-27) is associated with reduced
      disease-free survival in early stage breast cancer. Histopathologic evidence of
      confluent necrosis within primary infiltrating ductal carcinoma (IDC) is
      similarly an indication of poor prognosis. We postulated that IDC evidencing
      confluent tumor necrosis (TN) might overexpress this protein, which would help
      explain why hsp-27 is associated with higher-risk cancers. To test this
      hypothesis, presence of TN (as opposed to individual cell apoptosis) and of hsp
      27 expression by immunohistochemistry were evaluated independently in 48
      specimens of IDC. Nineteen (40%) overexpressed hsp-27 and 10 (21%) displayed
      necrosis. IDCs with areas of TN are less likely to overexpress hsp-27, suggesting
      a lack of association between these histoprognostic variables. This negative
      correlation, however, supports hsp-27 as an independent predictor of high-risk
      disease.

PMID- 8544454
TI  - Vascular complications of total abdominal perfusion and aortic stop-flow
      infusion.
AB  - During a 2 year period (1992-1993), 149 patients with advanced abdominal cancer
      underwent total abdominal ischemic perfusion (TAP) and stop-flow infusion (SFI)
      159 times in an attempt to achieve palliation. These procedures and aortic stop
      flow infusion require insertion of balloon catheters into the abdominal aorta and
      inferior vena cava by a transfemoral approach. Flow is arrested for 15 minutes,
      during which time chemotherapeutic agents are infused into the aorta, distal to
      the balloon occlusion. Femoral access is by a surgical incision. The passage of
      the catheters is guided by fluoroscopy. Some tumor response was observed in 35%
      of the patients. Ten patients had major vascular complications; two iliac artery
      aneurysms were lacerated and required emergency repair. There were two femoral
      artery false aneurysms that required surgical correction, one early and one late.
      Aortic dissection was detected in four patients, but these did not require
      surgical intervention. Two patients had thrombosis distal to the occluded vessel,
      both required surgical intervention. To reduce the incidence of these vascular
      complications we recommend: (1) a clinical and vascular laboratory evaluation
      before the procedure, and (2) angiography of normal flow in patients with
      underlying vascular disease.

PMID- 8544455
TI  - A dose-response relationship between the frequency of p53 mutations and tobacco
      consumption in lung cancer patients.
AB  - Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is
      suggested that p53 mutations are associated with smoking-induced lung
      carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse
      transcription-polymerase chain reaction-single strand conformation polymorphism
      (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking.
      Twenty-five (47%) of 53 lung cancers carried p53 mutations. A discriminant
      analysis showed that the Brinkman index (0.156) and gender (0.140) significantly
      influenced p53 mutations. Furthermore, there was a dose-response relationship
      between the quantity of cigarettes consumed and the frequency of p53 mutations in
      lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency
      of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We
      suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

PMID- 8544456
TI  - Medullary thyroid carcinoma experienced at Kanazawa University Hospital.
AB  - Eleven cases of medullary thyroid carcinoma (MTC), which were experienced at
      Kanazawa University Hospital between 1975 and 1993, were examined to correlate
      the clinical, histologic, and immunohistochemical findings. Seven patients were
      women and four men, and the mean age was 46.6 years. The mean follow-up was 88.3
      months. Three patients had familial non-multiple endocrine neoplasia (MEN) MTC
      (familial MTC unassociated with other endocrinopathies) and the remaining eight
      had sporadic disease. At the end of the observation period, six patients were
      alive without disease and four were alive with metastatic disease. One patient
      died of MTC 8.3 years after surgery. Thus, the 10-year survival and disease-free
      survival rates were 67% and 53%, respectively. Histologically MTCs from the 10
      surviving patients showed a classic type, while the one patient who died had a
      tubular variant MTC. Immunohistochemically, there were no significant
      correlations between the outcome of the patients and the expression of calcitonin
      (CT), carcinoembryonic antigen (CEA), calcitonin gene-related peptide (CGRP), or
      chromogranin A (CgA) in the primary tumors, and there were no differences in
      expression of these antigens between the primary and the recurrent tumors.
      Although only a small number of patients with MTC were studied here, it was
      suggested that the prognosis of MTC is worse than that of papillary and
      follicular thyroid carcinoma. The patients with lymph node involvement at the
      time of primary surgery showed a high risk of persistent or recurrent disease.
      The expressional level for the antigens did not influence the prognosis of MTC.

PMID- 8544457
TI  - Giant cell tumor of the proximal fibula: surgical management.
AB  - Five patients with giant cell tumor of the proximal fibula were treated with
      intralesional excision of the lesion, preservation of the peroneal nerve, and
      reconstruction of the lateral collateral ligament. At minimum 24-month follow-up
      there have been no local recurrences. Four patients exhibit normal function of
      the peroneal nerve and one has grade 4 strength of the muscles innervated by this
      nerve. No patient demonstrated varus instability. Marginal excision with nerve
      preservation and reconstruction of the ligament is a worthwhile procedure for
      treatment of this relatively uncommon lesion.

PMID- 8544458
TI  - Neoadjuvant chemotherapy in locally advanced breast cancer.
AB  - Thirty-eight patients with locally advanced breast cancer (Stage III) were
      treated over a 3-year period. All patients initially received two cycles of CMF
      (cyclophosphamide, 100 mg/m2 p.o. d1-14; methotrexate 40 mg/m2 intravenously
      (i.v.), d1 and d8., 5 Fluorouracil 500 mg/m2 i.v. d1 and d8). They were then
      subjected to surgery and external beam irradiation to the chest field and
      drainage areas. Four more cycles of chemotherapy completed the treatment
      protocol. A response to initial chemotherapy was seen in 75.7% patients, with two
      patients achieving a complete response. No patient had disease progression while
      on chemotherapy. Tumor reduction of a degree to allow breast conservation
      procedures was seen in eight patients. The chemotherapy was well tolerated.
      Twelve patients failed to complete the treatment protocol. Follow-up for the
      remaining 26 ranges from 9-40 months (mean 18 months). Ten patients developed a
      recurrence. Of those, only one had isolated local recurrence, two had local and
      systemic recurrence, and seven had systemic disease alone. Patients with
      recurrence were salvaged with further chemotherapy (Adriamycin and
      cyclophosphamide).

PMID- 8544459
TI  - Cytosine deaminase gene as a potential tool for the genetic therapy of colorectal
      cancer.
AB  - The bacterial enzyme cytosine deaminase (CD) catalyzes the conversion of 5
      fluorocytosine (5-FC) to the lethal 5-fluorouracil (5-FU) and so provides a
      useful system for selective killing of gene-modified mammalian tumor cells.
      Cloning of the CD gene from Escherichia coli and expression in human tumor cell
      lines enabled these cells to convert 3H-labeled 5-FC into 3H-5-FU. Two CD
      expressing human tumor cell lines (adenocarcinoma cell line KM12 and glioblastoma
      cell line T1115) became 200-fold more sensitive to 5-FC than the nonexpressing
      parental cell lines. At least 90% of the cells are killed within 7 days. CD
      expressing cells are able to kill nonexpressing cells when grown in the same
      culture flask (bystander effect). The CD gene may be used as a suicide system for
      in situ chemotherapy or as a safety mechanism abrogating the expression of other
      genes.

PMID- 8544460
TI  - Primary carcinoma of the gallbladder in Taiwan.
AB  - To define more precisely the prognostic index for patients with primary carcinoma
      of the gallbladder in Taiwan, we retrospectively reviewed the data of 74 patients
      with gallbladder carcinoma treated over a period of 15 years, from 1979 to 1993.
      Of these patients, 75% had Nevin stage V gallbladder cancer. The most common
      presenting complaint was abdominal pain, followed by jaundice, fever, and nausea
      and vomiting. Accurate preoperative diagnosis was made in 29.7% of the patients.
      Ultrasonography and computed tomography had a diagnostic accuracy of 34.0% and
      40.9%, respectively. The most common histologic type was adenocarcinoma. Liver
      was the organ most commonly invaded (51.9%) by direct extension and/or
      metastases, followed by regional lymph nodes (38.5%). The overall 5-year survival
      rate was 4.1%. Age, sex, white cell count, hemoglobulin, SGOT, SGPT, total
      bilirubin, alkaline phosphatase, and cholelithiasis were not significant
      prognostic factors. Patients with cancers confined in the gallbladder wall
      (stages I, II, III) had a better (P < 0.05) cumulative survival rate than did
      those with regional lymph nodes and distant metastases. Cholecystectomy or
      extended surgery had a better survival rate than did palliative surgery, but
      there was no significant difference between cholecystectomy and extended surgery.
      High index of suspicion of the disease and earlier surgical treatment may improve
      patient survival.

PMID- 8544461
TI  - Early thoracic duct ligation for postoperative chylothorax.
AB  - Four cases of postoperative chylothorax occurring at this institution over the
      past 5 years, as well as an extensive review of the world literature, are
      presented. Of the four cases, three occurred after resection of carcinoma of the
      lung and one after resection of recurrent chondrosarcoma of the chest wall. These
      patients were treated nonoperatively for varying periods of time ranging from 2
      days to nearly 3 weeks. Subsequently, all patients underwent ligation of the
      thoracic duct. Early reoperation for ligation of the thoracic duct resulted in no
      morbidity or mortality. In one case of delayed thoracic duct ligation, after an
      attempt at ligation of minor lymphatic vessels, the single mortality occurred. In
      view of the experience with these patients and that reported in the literature,
      we propose that not only is thoracic duct ligation superior to nonoperative
      management, but that it should be undertaken without delay.

PMID- 8544462
TI  - Metastatic endometrial carcinoma: rare cause of extrahepatic obstructive
      jaundice.
AB  - We report a very rare case of endometrial carcinoma causing extrahepatic bile
      duct obstruction. Management of this case and probable mechanism of spread are
      presented.

PMID- 8544463
TI  - Syndrome of inappropriate antidiuretic hormone secretion in papillary serous
      surface carcinoma of the peritoneum.
AB  - A case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in a
      patient with suboptimally cytoreduced stage III papillary serous surface
      carcinoma of the peritoneum is described. After the primary surgery, the patient
      refused further therapy. Within a month bilateral pleural effusions and abdominal
      ascites compelled the patient to accept treatment with carboplatin and
      cyclophosphamide. Ten days following the chemotherapy, she was admitted in a
      disoriented state with serum sodium of 117-mEq/L. During the evaluation,
      treatment, and subsequent follow-up, the diagnosis of SIADH was confirmed.
      Numerous disease processes have been associated with the development of SIADH;
      however, there have been few reports in gynecologic malignancies. Possible
      etiology and clinical management of this patient are briefly discussed.

PMID- 8544464
TI  - Preoperative localization in patients with difficult re-explorations for
      hyperparathyroidism.

PMID- 8544465
TI  - Rates of growth of human neoplasms: Part II.
AB  - Part I of this study [Spratt JS, Meyer JS, Spratt JA: J Surg Oncol 60:137-146,
      1995] reviewed the early reports of investigators, predominantly mathematical
      biologists and statisticians considering the mathematical laws that would
      describe the growth of a neoplasm. Included were cytokinetic measurements of the
      mitotic index, thymidine labeling index, bromodeoxy-uridine labeling index, and
      the relation of these indices to the potential tumor volume doubling time. The
      actual doubling time of benign and malignant colonic neoplasms were reported.
      This second part provides the cumulative observations on the actual doubling
      times of pulmonary metastases, primary pulmonary cancers, skeletal sarcomas,
      melanomas, a chemodectoma, tumors of maxillary antrum, testicular cancers,
      prostate cancer, and the relation between the accumulation of multiple primary
      cancers and growth rates. The most complete data set is for breast cancer
      concluding that the cancer growth curve is a decelerating curve with great
      natural variance. Understanding of the rates of growth of human cancers is
      essential for understanding the spectrum of cancer behavior observed clinically.

PMID- 8544466
TI  - Radical reoperation for advanced pancreatic carcinoma.
AB  - The indications and outcomes of aggressive reoperation in patients referred to
      the National Cancer Institute (NCI) for protocol therapy of locally advanced
      pancreatic carcinoma were investigated. Twenty-nine patients referred to the NCI
      after exploration and determination of unresectability elsewhere were considered
      to have localized disease after a metastatic work-up. These patients were then
      entered onto NCI adjuvant therapy protocols and taken to exploratory laparotomy.
      Intraoperatively, patients underwent complete resection if possible; otherwise
      varying palliative surgical procedures were performed. Of the 29 patients, 16
      underwent complete resection of their disease, and 13 were unresectable. Two
      patients suffered postoperative mortality. Disease-specific survival of the
      resected patients was significantly better than that of the unresectable patients
      (P < 0.01). The two long-term survivors (53 and > 109 months) underwent
      definitive surgery after a palliative procedure elsewhere. Complete resection of
      pancreatic carcinoma contributes to increased survival. The intraoperative
      definition of unresectability in pancreatic cancer varies with the degree of
      pancreatitis present, the surgical expertise of the surgeon, and the available
      ancillary services. Given the extremely grave prognosis of patients with
      unresectable pancreatic carcinoma, locally unresectable patients without
      peritoneal seeding of distant metastases at exploration should be considered for
      referral for protocol therapy to centers where expertise in radical surgery for
      pancreatic cancer exists.

PMID- 8544467
TI  - Extracellular glutamate: on-line monitoring using microdialysis coupled to enzyme
      amperometric analysis.
AB  - An enzyme-amperometric detector cell is described for flow analysis of glutamate
      in dialysate emerging from an implanted microdialysis probe. Its small size
      allows it to be placed within a few centimetres of the animal preparation,
      reducing the delay for data acquisition to around 2 min. The selectivity is
      provided by glutamate oxidase, immobilised with glutaraldehyde on surfaces
      adjacent to the 3-electrode system. A film of 1,2-diaminobenzene,
      electropolymerized on the platinum working electrode, eliminates interference
      from ascorbic acid and other endogenous electroactive compounds. The high
      sensitivity (< 0.5 mumol/l) and fast response time of the cell (90% of maximum
      response in 30 s) make it particularly suitable for investigating conditions that
      produce rapid changes in brain extracellular glutamate. This is illustrated by
      monitoring changes in extracellular glutamate subsequent to cardiac arrest, and
      K(+)-induced local depolarization.

PMID- 8544468
TI  - Phase locking of neuronal responses to the vertical refresh of computer display
      monitors in cat lateral geniculate nucleus and striate cortex.
AB  - The proliferation of low-cost microcomputer systems has led to the use of these
      systems as alternatives to expensive display devices for visual physiology and
      psychophysics experiments. The video displays of these systems often lack the
      flexibility of achieving wide linear luminance ranges and high vertical refresh
      rates--two parameters which may influence data acquisition. We have examined the
      responses of neurons and pairs of neurons in cat LGN and striate cortex to bar
      and sinusoidal grating stimuli generated by a conventional PC-based VGA graphics
      card and displayed on a NEC Multisync + color monitor with a 60 Hz vertical
      (display) refresh rate. Responses to these stimuli were autocorrelated and power
      spectral densities (PSD) were calculated, revealing that the majority of simple
      and complex cortical cells and nearly all LGN cells exhibited significant peaks
      in their autocorrelations at 16.7 ms and in the PSD at 60 Hz. Responses to
      identical stimuli generated with an optical bench using an incandescent light
      source contained no power at 60 Hz. Furthermore, cross-correlations between the
      spike trains of neuron-pairs were severely contaminated by peaks directly
      attributable to the entrainment of the two elements of the pair to the vertical
      refresh signal. Thus, we suggest that the use of conventional computer displays
      introduces a temporal artifact into neuronal spike trains in both single and
      multiple spike train analysis.

PMID- 8544469
TI  - Quantification of dendritic spine populations using image analysis and a tilting
      disector.
AB  - A series of image analysis routines, stochastic geometry methodology, and a
      design-based stereological procedure have been developed to quantify objectively
      the length, layout, and the true density of neuronal dendritic spines observed at
      the light (or confocal) microscope level. First, the image of a dendritic
      fragment of interest (in the plane of view) is scaled to a standard brightness
      scale, and the dendritic profile is separated from the background using a
      computerized thresholding algorithm that analyzes the histogram of grey levels.
      Secondly, the resulting binary image of the dendrite is transformed to a midline
      skeleton that underlies the dendritic geometry. Thirdly, skeletal branch lengths
      are directly computed (in pixels), thus giving objective measures of visible
      spine lengths and inter-spine distances along the dendritic stem. These raw data
      are the basis for (1) an estimation of the distribution of 3D spine lengths, and
      (2) a nearest neighbour analysis of the spine layout along the dendrite. A design
      based stereological routine, the tilting disector, is suggested for unbiased
      estimation of the true (3D) density of spines along dendrites. The routine
      involves tilting the dendritic fragment of interest around its longitudinal axis
      for a known angular sector and scoring the number of spines seen in one angular
      position and unseen in the other position. Data from a study of neuronal
      dendrites in the chick forebrain are presented.

PMID- 8544470
TI  - A two-channel action-potential generator for testing neurophysiologic data
      acquisition/analysis systems.
AB  - A 2-channel action-potential generator system was designed for use in testing
      neurophysiologic data acquisition/analysis systems. The system consists of a
      personal computer controlling an external hardware unit. This system is capable
      of generating 2 channels of simulated action potential (AP) waveshapes. The AP
      waveforms are generated from the linear combination of 2 principal-component
      template functions. Each channel generates randomly occurring APs with a
      specified rate ranging from 1 to 200 events per second. The 2 trains may be
      independent of one another or the second channel may be made to be excited or
      inhibited by the events from the first channel with user-specified probabilities.
      A third internal channel may be made to excite or inhibit events in both of the 2
      output channels with user-specified rate parameters and probabilities. The system
      produces voltage waveforms that may be used to test neurophysiologic data
      acquisition systems for recording from 2 spike trains simultaneously and for
      testing multispike-train analysis (e.g., cross-correlation) software.

PMID- 8544471
TI  - Characterisation of an experimental model of stroke produced by intracerebral
      microinjection of endothelin-1 adjacent to the rat middle cerebral artery.
AB  - A novel experimental model of stroke has been developed using the powerful
      vasoconstrictor peptide, endothelin-1, to occlude the middle cerebral artery
      (MCA) of anaesthetised rats. Intracerebral microinjections of endothelin-1 were
      administered under stereotaxic guidance adjacent to the MCA, and after 3 days
      rats were perfusion fixed for histopathological determination of ischaemic brain
      damage. The pattern of brain damage noted using this model was similar to that
      reported following permanent surgical occlusion of the MCA. Brain damage was
      apparent in the dorsal and lateral neocortex (98 +/- 12 mm3) and striatum (32 +/-
      3 mm3) ipsilateral to the insult. Rats anaesthetised with halothane and
      barbiturate exhibited a similar volume of brain damage. However, infarct volume
      increased when the duration of halothane anaesthesia was extended from 5 to 180
      min post-occlusion. Neuroprotection studies demonstrated that dizocilpine (5
      mg/kg, i.p.), administered 30 min prior to MCA occlusion, reduced the volume of
      cortical brain damage by 51% (P < 0.05) but did not alter the volume of striatal
      brain damage. The present results demonstrate that microinjections of endothelin
      1 adjacent to the rat MCA result in a reproducible pattern of focal cerebral
      infarction which is sensitive to the duration of anaesthesia and can be reduced
      by dizocilpine.

PMID- 8544472
TI  - Triple electrical channels on a triple fluid swivel and its use to monitor
      intracranial temperature with a thermocouple.
AB  - A low-torque, bubble-free and multiple-channel fluid swivel of easy construction
      was recently described. This paper describes the design, construction and testing
      of 3 electrical channels added to the original fluid swivel. The new channels
      were tested monitoring intrahypothalamic temperature (T(hy)) by means of a copper
      constantan thermocouple in freely moving rats, before and after a single
      intraperitoneal (i.p.) amphetamine injection (3 mg/kg). This test showed an
      increase in T(hy) after the injection and the maintenance of the electrical
      continuity along the whole testing period, even when the animals were
      hyperactive. With this improvement the original swivel was transformed in a more
      versatile device for experiments requiring fluid handlings and
      electrophysiological manipulations. Electrical stimulation as in kindling or
      brain self-stimulation, and electrophysiological recordings as in
      electroencephalography, electromiography, electrocardiography, in vivo
      voltammetry and even neuronal unit recording, are just examples of the
      electrophysiological methods that can be combined with drug self-administration
      and microdialysis using the present device.

PMID- 8544473
TI  - Detection of salicylate and its hydroxylated adducts 2,3- and 2,5
      dihydroxybenzoic acids as possible indices for in vivo hydroxyl radical formation
      in combination with catechol- and indoleamines and their metabolites in
      cerebrospinal fluid and brain tissue.
AB  - It has been suggested that salicylate (SA) hydroxylation can be used to detect
      hydroxyl radical formation in vivo. Here we describe a rapid and sensitive HPLC
      method using ultraviolet absorbance (UV) and electrochemical detection (EC) to
      detect SA (UV), its hydroxylated adducts 2,3- and 2,5-dihydroxybenzoic acids
      (DHBA) and catechol in combination with catechol- and indoleamines and related
      metabolites (EC) in one isocratic run. These compounds were measured in acidified
      cerebrospinal fluid (CSF) and perchlorate extracts of striatal tissues of
      untreated and SA-loaded rats (300 mg/kg SA, i.p.). Peaks were identified by
      comparing retention times of samples and standards, by adding standards to
      biological samples, by voltamograms, and by comparing chromatograms of manganese
      (Mn2+)-injected striata of SA-loaded rats with several control conditions. Six
      hours after unilateral injection of 0.4 mumol Mn2+ into striatum, 2,3-DHBA and
      2,5-DHBA levels in striatum were respectively 4- and 7-fold increased as compared
      to non-injected (contralateral) striata, suggesting in vivo hydroxyl radical
      formation. In addition, dopamine and serotonin levels were depleted in Mn(2+)
      injected striata by 46% and 64%, respectively. In CSF of Mn(2+)-injected rats,
      DHBA/SA ratios were not significantly changed as compared to those of control
      rats. In conclusion, the described technique can be applied to study in vivo
      hydroxyl radical formation in direct relation with dopaminergic and serotonergic
      neurotransmitter changes during neurotoxic processes.

PMID- 8544474
TI  - A new method of in-vivo microdialysis of the human brain.
AB  - In-vivo microdialysis has been used extensively to study the neurochemical
      mechanisms of ischemia, epilepsy and hypoglycemia. It is also being increasingly
      used to document the response of neurons to various medications. Most of the work
      to date has been done in small animals. In the last 2 years, the technique has
      been adapted for use in patients with subarachnoid hemorrhage, head trauma,
      Parkinson's disease, brain tumors and epilepsy. Two of the major limiting factors
      are the invasiveness of the technique and the resultant potential for CNS
      infection. We describe a simple, safe and reliable method to measure
      neurochemical changes in the human brain with in-vivo microdialysis. We were able
      to easily monitor for 4-6 h daily for up to 4 days in awake or comatose patients
      with subarachnoid hemorrhage or head trauma. Cerebral concentrations of
      glutamate, GABA, other amino acids and catecholamines were measured. This
      technique thus has a potential for on-line measurements of neurotoxins in
      patients with unstable neurological conditions.

PMID- 8544475
TI  - A feedback controlled silicon microprobe for quantitative mechanical stimulation
      of nerve and tissue.
AB  - The ability to apply and control the force and force velocity of mechanical
      stimulation is essential for the study of mechanoelectric transduction and
      adaptation processes. Silicon micromachining technology was used to produce
      miniature (20-70 microns wide) mechanical microprobes. Passive polysilicon,
      piezoresistive, force sensing elements were deposited onto the boron-doped
      epitaxial silicon and the individual devices were chemically etched from the bulk
      wafer. These microprobes display a linear force versus output voltage
      relationship. Stimulation forces up to 2 mN can be generated with a measurement
      resolution of 1.5 microN. The probes were mounted onto circuit board holders and
      their output sent to a proportional-integral controller which drives an
      electromagnetic actuator. By using this force-feedback control circuit coupled to
      a PC it is possible to define any stimulus wave form pattern and independently
      control and measure the actual stimulus force and velocity. A computer controlled
      3-axis stepper motor (0.025 micron step capability) manipulator is used to
      position the silicon microprobe-actuator assembly relative to the
      mechanoreceptive field. Sensor feedback control coupled to the 3-axis stepper
      motor manipulator allows automatic touchdown control and/or preloading of the
      probe prior to stimulation. Three-dimensional topographic manipulator feedback
      position control allows automated receptive field mapping.

PMID- 8544477
TI  - A practical vibration isolation workstation for electrophysiology.
AB  - Vibration control is a major concern in electrophysiological research,
      particularly during intracellular recording where movements of only a few
      micrometers may disrupt the cell membrane. The workstation described here is
      based on the concept of a table nested within a second table. The inner table
      supports a vibration-isolated surface while the outer table provides protection
      and a bench-top for equipment. The work surface is supported on squash balls in
      order to avoid the substantial cost of passive commercial isolators. The
      properties of the squash ball isolators were found to be similar to a set
      commercial isolators when compared with respect to impulse response, compliance
      and transmissibility. The table has been successfully used for both intra- and
      extracellular recording over a 3-year period. Work efficiency was enhanced by the
      close proximity of the bench-top and isolated work surface, while perimeter
      protection helped maintain stable recordings.

PMID- 8544476
TI  - Combining laser Doppler flowmetry with microdialysis: a novel approach to
      investigate the coupling of regional cerebral blood flow to neuronal activity.
AB  - Regional cerebral blood flow (rCBF) is directly coupled to neuronal activity;
      however, the mediators of this coupling have not been established. The
      characterization of these vasoactive substances requires a technique which
      enables sampling of locally released mediators together with the simultaneous
      monitoring of rCBF. The goal of this study was to establish such a technique by
      combining microdialysis and laser doppler flowmetry. Laser doppler and
      microdialysis probes were inserted into the dorsal hippocampal, CA1-dentate
      hilus, of rats. Animals received sequentially increasing concentrations of N
      methyl-D-aspartate (NMDA). rCBF responded in a dose-dependent manner, increasing
      to 106.8 +/- 2.3%, 119.7 +/- 6.3%, 148.0 +/- 16.6%, and 191.4 +/- 20.4% of
      baseline at 50 microM, 100 microM, 200 microM, and 500 microM NMDA, respectively.
      All doses of NMDA produced an increase in extracellular concentrations of
      adenosine and citrulline, an indirect measure of nitric oxide generation. These
      results indicate that the combination of microdialysis and laser doppler
      flowmetry is a valuable tool to investigate the coupling of rCBF to neuronal
      activity. Moreover our data suggest two possible mediators of this coupling,
      nitric oxide and adenosine, which require further investigation.

PMID- 8544478
TI  - Antisense oligodeoxyribonucleotides: stability and distribution after
      intracerebral injection into rat brain.
AB  - As a prerequisite for blocking specific gene expression in the brain, the
      pharmacokinetics of two radiolabelled analogs of antisense
      oligodeoxyribonucleotides (unmodified O-ODN and nuclease resistant
      phosphorothioate S-ODN) were examined by infusion into the baso-lateral nucleus
      of amygdala. Both ODN analogs were found to penetrate at restricted distances
      into the brain tissue. Rapidly after injection, O-ODN was almost completely
      degraded, while S-ODN remained intact up to 24 h following administration as
      examined by gel electrophoresis of nucleic acids recovered from the injection
      site. The tissue clearance of the radioactivity delivered in a form of O-ODN and
      S-ODN was also different, the former characterized by much better tissue
      retention. Microscopic studies suggested that S-ODN can apparently penetrate
      across the cell membrane and accumulate both in the cytoplasm in the cell
      nucleus. In situ hybridisation histochemistry experiments (antisense probe to
      injected ODN) revealed that injected S-ODN was present in a form available for
      annealing with the complementary strand. Our results provide a basic description
      of the distribution, retention, and stability of antisense oligonucleotides
      injected into brain tissue.

PMID- 8544479
TI  - Quantitative microdialysis of neuropeptide Y.
AB  - The feasibility of using the difference method of quantitative microdialysis to
      measure neuropeptide Y (NPY) was evaluated in vitro and in vivo. The accuracy of
      this method was tested in vitro under steady-state conditions for 3 test
      solutions containing known concentrations of NPY. The estimated concentrations of
      NPY were 1.2 +/- 0.6, 3.7 +/- 0.9, and 15.1 +/- 0.7 pg/microliter (mean +/- SEM)
      in agreement with the actual concentrations of NPY in the test solutions which
      were 1.1 +/- 0.8, 4.6 +/- 0.6, and 14.6 +/- 0.5 pg/microliter (mean +/- SEM of
      solution samples), respectively. The responsiveness of the estimated NPYext
      measure to changes in the external concentration of NPY was also evaluated in
      vitro. An accurate estimate of NPYext was obtained within the first sampling
      period (within 15 min) after a 2-3-fold increase in the test solution
      concentration of NPY and within 2-3 sampling periods (15-45 min) in response to a
      2-3-fold decrease in the test solution concentration of NPY. In vivo, the
      estimated basal concentration of NPY in dialysis samples from probes in the
      medial basal hypothalamus of anesthetized female rats (n = 4) was 4.0 +/- 1.6
      pg/microliters and increased to 9.5 +/- 0.3 pg/microliter during K+ stimulation.
      Relative recovery was 22% in vivo under steady-state conditions and ranged from
      14% to 30% during dynamic conditions. These results demonstrate that the
      difference method of quantitative microdialysis accurately estimates picomolar
      concentrations of NPY in vitro, and is sufficiently sensitive to detect basal and
      increasing concentrations of NPY in vivo.

PMID- 8544480
TI  - A motion tracking system for simultaneous recording of rapid locomotion and
      neural activity from an insect.
AB  - We have adapted techniques for studying the locomotion of tethered insects to
      analysis of rapid directional movements such as escape behavior. We describe here
      a computer-based motion tracking system that allows an animal to turn and run as
      rapidly as it does under free-ranging conditions, and that samples fast enough to
      accurately reconstruct the movements. Furthermore, we have designed chronic
      electrodes that allow for simultaneous extracellular recording of the activity of
      interneurons related to behavior. We used this system to record the escape
      response of tethered cockroaches, Periplaneta americana, and compared the data
      with those obtained from high-speed videographic analysis of the same animals
      under free-ranging conditions. In the motion tracking system, animals were
      normally responsive to sensory input, and expressed directional escape turning
      responses. This system allows details of an entire escape response (initial turn
      and subsequent running) to be quantified. These behavioral details can now be
      correlated with the discharge of key interneurons on a trial-by-trial basis.

PMID- 8544481
TI  - Manufacture and release characteristics of Elvax polymers containing glutamate
      receptor antagonists.
AB  - Implantable sustained-release polymers offer an alternative to osmotic minipumps
      for the local delivery of drugs to specific brain areas. Here we describe the
      production of Elvax polymers containing a range of glutamate receptor antagonists
      and the quantitative characterization of their release properties. Sections of
      Elvax (200 or 400 microns), prepared by a dimethyl sulphoxide-based method,
      containing the NMDA antagonist MK-801 or the non-NMDA antagonist CNQX exhibited
      similar release profiles: an initial 2-week burst followed by a slow decline in
      release rate over the next 6 weeks. Differences in slice preparation method and
      thickness or drug concentration and solubility all led to alterations in the
      level of drug release, but not the overall exponential nature of the release
      curve. Elvax sections prepared by an aqueous method containing the NMDA
      antagonists CPP or APV displayed more constant but much lower levels of release
      than those from the dimethyl sulphoxide-based method. The in vitro release
      characteristics were compared with in vivo release of MK-801 and the close
      correspondence observed indicates that the in vitro release data is an accurate
      predictor of the drug release behaviour of implanted Elvax slices.

PMID- 8544482
TI  - An ex vivo rat retinal preparation for excitotoxicity studies.
AB  - Although the isolated chicken embryo retina has been a very useful in vitro
      preparation for studying mechanisms of excitotoxicity, it is an avian rather than
      mammalian tissue and its embryonic age makes it unsuitable for a full range of
      developmental and aging studies. Therefore, we have explored the feasibility of
      using the rat retina at various ages for in vitro excitotoxicity studies. In this
      model, retinal segments were isolated in artificial cerebrospinal fluid (CSF) at
      5 degrees C then incubated under various conditions at 30 degrees C and assessed
      histologically for signs of neurodegenerative changes. Retinal segments from 7-,
      30-, 120- and 660-day-old rats incubated in CSF for 3 h and from 30-day-old rats
      incubated for 24 h retained a normal histological appearance. Thus, this
      preparation is suitable for in vitro studies pertaining to either acute or
      delayed excitotoxic phenomena in the mammalian CNS at any age from infancy to old
      age. Excitotoxin agonist experiments in the 30-day-old rat retina revealed the
      surprising result that the non-NMDA agonists, kainate and AMPA, at a low
      concentration (100 microM) damaged a much larger number of retinal neurons than
      NMDA did at a very high concentration (10 mM).

PMID- 8544483
TI  - Dorsal spinocerebellar tract neuronal activity in the intact chronic cat.
AB  - The ability to electrophysiologically identify the axonal projections of lumbar
      neurons recorded in chronic unanesthetized intact awake animals is a formidable
      but essential requirement toward understanding ascending sensory transmission
      under naturally occurring conditions. Chronic immobilization procedures
      previously introduced by Morales et al. (1981) for intracellular studies of
      motoneurons are modified and then integrated with procedures for antidromic
      cellular identification and extracellular recording of upper (or lower) dorsal
      lumbar spinocerebellar tract (DSCT) neuronal activity, in conjunction with
      behavioral state recording and drug microiontophoresis. These implant procedures
      provide up to 6 months of stable recording conditions and, when combined with
      other techniques, allow individual DSCT neurons to be monitored over multiple
      cycles of sleep and wakefulness, following the induction into and recovery from
      barbiturate anesthesia and/or during the juxtacellular microiontophoretic
      ejection of inhibitory or excitatory amino acid neurotransmitters. The
      combination of such techniques allows a comprehensive examination of synaptic
      transmission through the DSCT and other lumbar sensory pathways in the intact
      normally respiring cat and its modulation during the general anesthetic state.
      These techniques permit investigations of the supraspinal controls impinging on
      lumbar sensory tract neurons during wakefulness and other behavioral states such
      as active sleep.

PMID- 8544484
TI  - A computer-controlled maze environment for testing visual memory in the rat.
AB  - A computer-controlled version of a Y-maze was developed to allow automated
      testing of rats' learning and memory with visual stimuli. Each of the 3 arms
      terminated with 2 adjacent monochromatic screens, 43 cm from the maze centre,
      providing a total stimulus area 47 cm wide by 18.5 cm high. The displays were
      abstract patterns extending across 2 screens, generated by algorithms which
      provided a large pool of discriminable patterns. The patterns used were of 2
      general classes: Scenes (internally complex patterns with varying numbers of
      foreground shapes distributed across contrasted backgrounds) and Objects
      (internally homogeneous single figures, confined to the central part of the
      display). They could be stationary or have oscillatory movement. Subjects'
      location in the maze was monitored by infrared beam photodetectors; approach to
      correct patterns was rewarded with food. Pigmented rats of the Hooded Lister and
      Dark Agouti strains were tested. All could acquire 2-pair concurrent visual
      discriminations comprising 2 positive and 2 negative patterns, either Scenes or
      Objects; most could acquire 4-pair discriminations. Dark Agouti rats generally
      performed better than Hooded Listers. A novel training procedure using one
      positive and many negative patterns resulted in rapid learning of novel
      discriminations with either moving or non-moving patterns. The apparatus is an
      effective environment for visual learning by rats, suitable for a wide range of
      tasks in neuropsychology and psychopharmacology.

PMID- 8544485
TI  - A fast and easy fluorescent counterstaining method for neuroanatomical studies by
      using Acridine Orange.
AB  - Acridine Orange is commonly used as a fluorescent counterstain in fluorescent
      tract tracing techniques. Here we describe a method in which the substitution of
      the standard washing solutions (i.e., 0.9% saline) for a diluted solution of
      Acridine Orange (0.001%) during the perfusion of the animal before fixation
      provides a fluorescent counterstaining compatible with Fast Blue fluorescent
      retrograde labeling. In contrast to other fluorescent counterstaining methods,
      this procedure minimizes the diminution in the fluorescence of the tracer during
      the handling of sections.

PMID- 8544486
TI  - An improved autoradiographic coating technique for neurohistopathological stains
      and electron microscopy.
AB  - We describe modifications and improvements to our first report of a new nuclear
      emulsion coating technique for both light and electron microscopic
      autoradiography. Although this technique was originally designed to facilitate
      electron microscopic autoradiography, the methodology also allows pre-staining of
      plastic-embedded tissue sections prior to coating the slides with nuclear
      emulsion for light microscopic autoradiography. We now demonstrate that paraffin
      sections can be autoradiographically processed after being subjected to a
      combination of immunocytochemical reactions and special neuroanatomical strains.
      Parlodion film has been found to be more resistant to temperature changes and
      less prone to contamination than Formvar film. The shape of the double adhesive
      tape is an important aspect of the electron microscopic technique; it has been
      modified to minimize contamination and facilitate the removal of the grids from
      the glass slide. These technical adjustments facilitate the application of the
      nuclear emulsion and increase radionuclide specificity, thus expanding the
      investigative horizons of light and electron microscopic autoradiography.

PMID- 8544487
TI  - Simultaneous optical recording of evoked and spontaneous transients of membrane
      potential and intracellular calcium concentration with high spatio-temporal
      resolution.
AB  - We have developed a system for simultaneous optical recording of transients of
      membrane potential and intracellular calcium concentration from mammalian brain
      slice preparations with high spatio-temporal resolution. Simultaneous recording
      was achieved by using two dedicated photodetectors together with two fluorescent
      indicators. Specifically, the calcium-sensitive dye Calcium Orange and the
      voltage-sensitive dye RH-414 were selected because they have overlapping
      excitation spectra, but separable emission spectra. Transverse guinea pig
      hippocampal slices were double-loaded by bath application of the membrane
      permeant form of Calcium Orange and RH-414. Transients of intracellular calcium
      concentration and membrane potential associated with evoked neural activity in
      hippocampal areas CA1 and CA3 were recorded. Furthermore, we have recorded
      calcium and voltage transients associated with spontaneous epileptiform activity
      induced by bath application of an epileptogenic drug, 4-aminopyridine. The use of
      photodiode matrices (10 x 10 elements each) as detectors gives the high spatial
      (200 x 200 microns/element with a 10 x objective) and temporal resolution (570
      microseconds/frame). The recording system also includes a CCD camera for
      obtaining images of the preparation and overlaying the image with the optically
      detected signals. A software package has been developed for setting up the
      experimental protocol(s) and for collecting, processing, displaying, and
      analyzing the data in an user-friendly, windows-based environment.

PMID- 8544488
TI  - An electromechanical stimulator system for neurophysiological and psychophysical
      studies of pain.
AB  - We have developed a computer-based electromechanical stimulator system suited for
      neurophysiological and psychophysical studies of pain. The core of the stimulator
      is a servo-controlled linear motor capable of generating 1 kg of force over a 22
      mm range. Forces collinear and tangenital to the interchangeable probe tip are
      calculated using the signal from 3 load cells (resolution: 1/8 g; range: 250 g)
      arranged in an equilateral triangle. Probe position is measured with an optical
      encoder (resolution: 1 micron; range: 25 mm). A microprocessor-based digital
      control system permits smooth switching of feedback control between force or
      position at the 1-kHz update rate. The stimulator is mounted on a microprocessor
      controlled 3-axis translation system that allows automatic movement of the probe
      over a range of greater than 15 cm to an accuracy of better than 10 microns. The
      stimulator can be programmed to move in a coordinate system parallel to the skin
      surface being examined. An IBM-compatible computer is used to command stimulus
      paradigms and to display real-time motor performance and neural spike-train data.
      The system has been used to measure the response of nociceptive afferents in
      monkey to controlled force stimuli applied to various positions within the
      receptive field.

PMID- 8544489
TI  - Linear prediction and single-channel recording.
AB  - The measurement of individual single-channel events arising from the gating of
      ion channels provides a detailed data set from which the kinetic mechanism of a
      channel can be deduced. In many cases, the pattern of dwells in the open and
      closed states is very complex, and the kinetic mechanism and parameters are not
      easily determined. Assuming a Markov model for channel kinetics, the probability
      density function for open and closed time dwells should consist of a sum of
      decaying exponentials. One method of approaching the kinetic analysis of such a
      system is to determine the number of exponentials and the corresponding
      parameters which comprise the open and closed dwell time distributions. These can
      then be compared to the relaxations predicted from the kinetic model to
      determine, where possible, the kinetic constants. We report here the use of a
      linear technique, linear prediction/singular value decomposition, to determine
      the number of exponentials and the exponential parameters. Using simulated
      distributions and comparing with standard maximum-likelihood analysis, the
      singular value decomposition techniques provide advantages in some situations and
      are a useful adjunct to other single-channel analysis techniques.

PMID- 8544490
TI  - A diffusion-reaction model of nerve regeneration.
AB  - The process of peripheral nerve regeneration has been modeled using 5 populations
      of mathematical variables to represent the biological activities of Wallerian
      degeneration, fibrin matrix development, Schwann cell activity, elongating
      neurites, and neovascularization. The mathematical model provided simulations of
      nerve regeneration following transection and crush injuries that correspond with
      growth behaviors quantified in biological experiments. Neovascularization was
      spatiotemporally quantified in nerve regeneration chambers and following nerve
      crush injury in order to test the simulations of the mathematical model. The
      vasculature in both the chamber and following nerve crush responded as predicted
      by the model, increasing beyond normal levels to a peak only to decrease back to
      normal. This behavior appeared as a traveling wave in the proximal-distal
      direction preceeding the major thrust of neuritic outgrowth suggesting that
      development of the vasculature is a rate-limiting step in nerve regeneration.

PMID- 8544492
TI  - Defining stops in search pathways.
AB  - The alternation of stationary periods and periods of movement may be an important
      feature of an animal's search tactic. Unambiguously differentiating stops and
      moves may be difficult, especially from highly resolved digitized pathways, but
      their identification may be essential for understanding an animal's searching
      behavior. In this paper, we describe a method for defining stops in search
      pathways. A computer program that identifies the stop-and-go movement patterns
      from digitized pathway data is available upon request from the authors.

PMID- 8544491
TI  - A laser interferometer for sub-nanometre measurements in the cochlea.
AB  - A modification of a light microscope is described here which allows measurement
      of nanometre movements along the optical axis of the microscope. The light path
      is reflected off 10-microns-diametre small glass beads which are individually
      imaged with the microscope objective. The interferometer is under computer
      control to allow it to remain in quadrature and so maximise sensitivity. The
      algorithm is described. Although the techniques are applied to detection of
      movements of the cochlear partition, they can be used to measure sub-micron
      movements of any reflecting structures accessible to microscopy.

PMID- 8544493
TI  - A simple dual pressure-ejection system and calibration method for brief local
      applications of drugs and modified salines.
AB  - We report a minimal method for dual pressure ejection through a single
      micropipette, which uses standard theta-type glass tubing and a connection
      through thinned polythene catheters without any sealing. We also describe a
      simple calibration method using a standard electrometer. The linearity of the
      ejected volume with respect to pulse duration and to applied pressure was
      maintained, as measured by the resistivity of ultrapure water after ejection of a
      saline solution. The method was used to analyse the inhibitory effect of
      glutamate on crayfish motoneurones with local and reversible applications of low
      chloride saline and picrotoxin.

PMID- 8544494
TI  - [Illegal immigrants in France are denied health care. Non-profit medical
      organizations open their own surgeries].

PMID- 8544495
TI  - [ISO 9000, TQM, Kaizen, Noll fel... May health care learn something from
      industry?].

PMID- 8544496
TI  - [The National Social Insurance Board: why new forms for certificates of
      illness?].

PMID- 8544497
TI  - [Offering mammography is beneficial in the long run].

PMID- 8544498
TI  - [Physicians disagree when your certificate of illness is questioned!].

PMID- 8544499
TI  - [What constitutes doping?].

PMID- 8544500
TI  - [Safety of plasma products may be improved].

PMID- 8544501
TI  - [ Unlimited cooperation].

PMID- 8544502
TI  - [Regional stroke care program].

PMID- 8544503
TI  - [Is intermittent oxygen therapy effective as palliative treatment?].

PMID- 8544504
TI  - [Interns are future skilled specialists].

PMID- 8544505
TI  - [Oral contraceptives and thrombosis--a comment].

PMID- 8544506
TI  - [The conscious and the unconscious olfactory perception].

PMID- 8544507
TI  - [Which are the infections dangerous to society?].

PMID- 8544508
TI  - [Confused by memories and their own mind? Widows and widowers often experience
      deep grief and feeling of loss].

PMID- 8544509
TI  - [Pictures of the psyche. Imaging the highest functions of the brain:
      consciousness, language, emotions, is now possible].

PMID- 8544511
TI  - [Asklepios--god-physician with human weaknesses. He was seduced by the gold to go
      beyond the permitted limits].

PMID- 8544510
TI  - [History of hearing perception. Different shapes of hearing aids: from the
      "cupped hand" to cochlear implants].

PMID- 8544512
TI  - [Endothelin--a vasoactive peptide and growth factor].

PMID- 8544513
TI  - [Johannes Chesnecopherus. Sweden's first professor of medicine].

PMID- 8544514
TI  - [In the footsteps of plague-carrying fleas in the old empire of Genghis Khan-
      report from a Mongolian city].

PMID- 8544515
TI  - [A true story about emergency care in a region without roads: a 30-mile trip for
      a surgeon and a nurse with the help of an extra-train and rented motorcycles].

PMID- 8544516
TI  - [May sumatriptan cause cerebral infarction?].

PMID- 8544517
TI  - [Aethoxysterol].

PMID- 8544518
TI  - [Myalgia during treatment with Cozaar].

PMID- 8544519
TI  - [Beliefs and knowledge of medicine, or how to become a "successful" practitioner
      of naturopathy].

PMID- 8544520
TI  - [Fight the administrators that cuts the resources! Concentrate on autonomous
      units!].

PMID- 8544522
TI  - [Wrong criticism of anatomic description of the hand].

PMID- 8544521
TI  - [A new element presented at a medical congress. Violation of autonomy may cause
      disease].

PMID- 8544523
TI  - [Short-term cost savings do not constitute good economy!].

PMID- 8544524
TI  - [Important notice: normal dosage of Teldanex is halved].

PMID- 8544525
TI  - [Obesity--a public disease].

PMID- 8544526
TI  - [Tacrine against Alzheimer disease? Still uncertain for which patients may the
      treatment be beneficial].

PMID- 8544527
TI  - [Thalassemia, heading for Sweden. A new patient group at Swedish pediatric
      clinics].

PMID- 8544528
TI  - [Creating new words is better than defining with non-words].

PMID- 8544529
TI  - [The fat should be located in body regions on which we sit].

PMID- 8544530
TI  - [High level of protein in Swedish food. A health risk?].

PMID- 8544531
TI  - [Should disposable products be reused? The "re-user" takes big risks].

PMID- 8544532
TI  - [The most-attended meeting on Chernobyl ever. Markedly increasing number of
      thyroid cancer cases among children and adolescents].

PMID- 8544533
TI  - [Microbiology, penetrating deeply into the world of microbes. Basic changes in
      the treatment of infections].

PMID- 8544534
TI  - [Androgens in the treatment of women].

PMID- 8544535
TI  - [Insurance medicine--prognosis medicine].

PMID- 8544536
TI  - ["Being alive is to build bridges". German physician-writers during over four
      centuries].

PMID- 8544537
TI  - [High-frequency oscillatory ventilation. A successful ventilatory techniques used
      in pediatric surgery].

PMID- 8544538
TI  - [Pharmacotherapeutic recommendation for depression. Newer preparations are
      recommended, especially in primary health care. Lakemedelsverket (Swedish Drug
      Authority)].

PMID- 8544539
TI  - [Finland is a leading country when it comes to telemedicine].

PMID- 8544540
TI  - Have you had a gene test?

PMID- 8544541
TI  - The infected metropolis.

PMID- 8544542
TI  - The semantics of pressure.

PMID- 8544544
TI  - Government assault on Canada's physicians.

PMID- 8544543
TI  - Origins of coronary artery ectasia.

PMID- 8544545
TI  - Pseudo-outbreaks.

PMID- 8544546
TI  - Lack of reproducibility in pregnancy of Korotkoff phase IV as measured by mercury
      sphygmomanometry.
AB  - BACKGROUND: Since hypertensive disorders of pregnancy are common, blood pressure
      is frequently measured in all pregnant women. Many authorities recommend that
      Korotkoff phase IV (K4, muffling of sound) is taken as the diastolic
      identification point measured on mercury sphygmomanometry in pregnancy because of
      reports that phase V (K5, disappearance of sound) is at or near to zero cuff
      pressure in some pregnant women. We compared the identification and
      reproducibility of K4 and K5 by observers unaware of each other's results.
      METHODS: In the first part of the study, two pairs of observers each took 340
      measurements in 85 pregnant women. The second part of the study consisted of 1120
      measurements in 80 pregnant and 80 non-pregnant women by five pairs of observers.
      Measurements were taken simultaneously by sphygmomanometry with a shared cuff and
      diaphragm; the observers were in separate booths. FINDINGS: K5 was identified in
      all measurements by both observers and never approached zero. K4 was heard in
      only 52% of measurements; in 33% of cases it was heard by only one of the pair of
      observers, so the pair agreed on its detection in only 19% of readings. Visual
      analogue scores used to assess Korotkoff sound quality indicated that systolic
      blood pressure was perceived significantly more clearly than diastolic blood
      pressure (K4 or K5). Even when K4 was heard by both observers, agreement on its
      value was poor (78% within 5 mm Hg vs 86% for K5, p < 0.05). K4 was heard
      significantly less often in non-pregnant women (32% of measurements). There was
      also no consistency in the identification of K4 within individual women.
      INTERPRETATION: K4 has little value in clinical management because it cannot be
      reproduced accurately. We recommend that K4 should be replaced by K5 as the
      measure of diastolic blood pressure in pregnancy.

PMID- 8544547
TI  - Randomised trial of oral morphine for chronic non-cancer pain.
AB  - BACKGROUND: The use of opioid analgesics for chronic non-cancer pain is
      controversial. Some surveys report good pain relief and improvement in
      performance while others suggest a poor outcome with a propensity to
      psychological dependence or addiction. METHODS: We undertook a randomised double
      blind crossover study to test the hypothesis that oral morphine relieves pain and
      improves the quality of life in patients with chronic regional pain of soft
      tissue or musculoskeletal origin who have not responded to codeine, anti
      inflammatory agents, and antidepressants. Morphine was administered as a
      sustained-release preparation in doses up to 60 mg twice daily and compared with
      benztropine (active placebo) in doses up to 1 mg twice daily over three-week
      titration, six-week evaluation, and two-week washout phases. Pain intensity, pain
      relief, and drug liking were rated weekly and psychological features, functional
      status, and cognition were assessed at baseline and at the end of each evaluation
      phase. FINDINGS: After dose titration in the 46 patients who completed the study,
      the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On
      visual analogue scales, the morphine group showed a reduction in pain intensity
      relative to placebo in period I (p = 0.01) and this group also fared better in a
      crossover analysis of the sum of pain intensity differences from baseline (p =
      0.02). No other significant differences were detected. INTERPRETATION: In
      patients with treatment-resistant chronic regional pain of soft-tissue or
      musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily
      may confer analgesic benefit with a low risk of addiction but is unlikely to
      yield psychological or functional improvement.

PMID- 8544548
TI  - Prenatal screening for cystic fibrosis: 5 years' experience reviewed.
AB  - BACKGROUND: Although several programmes of prenatal screening for cystic fibrosis
      have been completed and reported, there are still uncertainties about rates of
      take up and also about the action of parents identified as having a one-in-four
      risk of an affected child. I report 5 years' experience with the two-step and
      couple models of prenatal screening of cystic fibrosis. METHODS: Screening has
      been available at two antenatal clinics in Edinburgh, UK, since January, 1992,
      first on a research basis and then routinely. 25,000 couples have been screened.
      FINDINGS: Take-up rates for the two-step and couple models of delivery are very
      similar at about 70%. Take-up rates did not change when screening moved from a
      research to a routine service. Of 22 high-risk couples identified entirely
      through screening, 20 (91%) opted for prenatal diagnosis. Four couples returned
      for second and two for third monitored pregnancies. In all eight cases where
      affected fetuses were identified, pregnancy was terminated. INTERPRETATION: These
      data remove one of the few remaining obstacles to a general implementation of
      prenatal screening for cystic fibrosis.

PMID- 8544549
TI  - Psychometric scores and persistence of irritable bowel after infectious
      diarrhoea.
AB  - BACKGROUND: Although previous studies have shown that psychological disturbances
      are frequently associated with the irritable bowel syndrome (IBS), the relation
      was not necessarily cause and effect. The development of chronic bowel symptoms
      resembling IBS after an episode of acute gastroenteritis has allowed us to
      examine prospectively the role of psychological factors. METHODS: 75 patients
      with acute gastroenteritis completed a series of psychometric tests soon after
      admission to hospital. Of these, 22 had persistent symptoms compatible with IBS
      after the acute illness, and in 20 of these the symptoms were still present at
      six months. FINDINGS: At the time of their initial illness, patients who
      subsequently developed IBS symptoms had higher scores for anxiety, depression,
      somatisation, and neurotic trait than those who returned to normal bowel
      function. The psychometric scores had not changed when remeasured three months
      after the acute illness. Lactose malabsorption was not an important factor.
      INTERPRETATION: These results support the hypothesis that psychological factors
      are important in IBS.

PMID- 8544550
TI  - Common-source outbreak of acute infection due to the North American liver fluke
      Metorchis conjunctus.
AB  - BACKGROUND: We investigated an outbreak of acute clinical illness among 19 people
      who ate raw fish (sashimi) prepared from the white sucker, Catostomus commersoni,
      caught in a river north of Montreal, Canada. METHODS: We collected
      epidemiological, clinical, laboratory, and serological data on 19 individuals who
      ate the sashimi and six who did not. Because of the suggestive clinical picture,
      we set out to recover helminth parasites from uneaten fish. FINDINGS: The illness
      consisted of persistent upper abdominal pain, low grade fever, high blood
      eosinophil concentrations, and raised liver enzymes. After 10 days, opisthorchild
      like eggs were found in stools. Symptoms persisted for 3 days to 4 weeks without
      treatment, but responded rapidly to praziquantel therapy. Necropsy of golden
      hamsters infected with metacercariae from uneaten fish revealed adult flukes
      identified as Metorchis conjunctus. INTERPRETATION: We describe an acute illness
      caused by the North American liver fluke M conjunctus. This is a new human
      disease and is the first report of a common-source outbreak of an acute illness
      caused by liver flukes of the family Opisthorchiidae.

PMID- 8544551
TI  - Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron
      disease.
AB  - BACKGROUND: Variants of the apolipoprotein E (APOE) gene influence the age of
      onset of Alzheimer's disease. APOE may influence the presentation of other
      neurological diseases. We investigated the relationship between the allelic
      variants of apolipoprotein E and clinical presentation in motor neuron disease.
      METHODS: 123 patients with motor neuron disease and 121 controls were studied.
      Diagnosis, location of onset and date of onset were recorded prospectively.
      Genotyping was performed blind to clinical information. FINDINGS: Possession of
      at least one epsilon 4 allele was significantly more common in patients with
      bulbar onset motor neuron disease (14/33, 42%) than in limb onset patients
      (20/90, 22%) and controls (26/121, 21%) (chi 2 = 4.93, p = 0.026 and chi 2 =
      5.91, p = 0.015, respectively). INTERPRETATION: These results suggest that the
      apolipoprotein E epsilon 4 allele may influence the pattern of motor neuron loss
      in motor neuron disease and that it may affect neuronal function in ways
      unrelated to the deposition of beta-amyloid or accumulation of neurofibrillary
      tangles.

PMID- 8544552
TI  - Hypercalcaemia with lymphoedema.

PMID- 8544553
TI  - The disease called addiction: emerging evidence in a 200-year debate.

PMID- 8544554
TI  - Ludwig van Beethoven: a medical biography.

PMID- 8544555
TI  - Patients' preferences and randomised trials.

PMID- 8544556
TI  - How to ensure the continued resurgence of tuberculosis.

PMID- 8544557
TI  - Was HIV present in 1959?

PMID- 8544558
TI  - Porphyria cutanea tarda preceding AIDS.

PMID- 8544559
TI  - HIV transmission by donor semen.

PMID- 8544560
TI  - Fetal antigen 1 and growth hormone in pituitary somatotroph cells.

PMID- 8544561
TI  - Intermittent maple syrup disease.

PMID- 8544562
TI  - Serum, breast milk, and infant antibody after maternal immunisation with
      pneumococcal vaccine.

PMID- 8544563
TI  - Incidence of insulin-dependent diabetes among Sardinian migrants to northern
      Italy.

PMID- 8544564
TI  - False memory syndrome.

PMID- 8544565
TI  - Interferon and hepatocellular carcinoma.

PMID- 8544567
TI  - UK adults' risk from eating beef.

PMID- 8544566
TI  - Interferon and hepatocellular carcinoma.

PMID- 8544568
TI  - Neuroprotection in Parkinson's disease.

PMID- 8544569
TI  - Outcome of an enterohaemorrhagic Escherichia coli O157 infection in monozygotic
      twins.

PMID- 8544570
TI  - Endomyocardial fibrosis: why is there striking ascites with little or no
      peripheral oedema?

PMID- 8544571
TI  - Sanctions against Iraq.

PMID- 8544572
TI  - Sanctions against Iraq.

PMID- 8544573
TI  - Sanctions against Iraq.

PMID- 8544574
TI  - Sanctions against Iraq.

PMID- 8544575
TI  - "Health hazards" and the media.

PMID- 8544576
TI  - Sanctions against Iraq.

PMID- 8544577
TI  - Childhood poisonings from ingestion of cigarettes.

PMID- 8544578
TI  - Standardised mortality ratios.

PMID- 8544579
TI  - Extracorporeal membrane oxygenation for refractory shock in fulminant
      meningococcal sepsis.

PMID- 8544580
TI  - Early haemo-diafiltration in meningococcal septicaemia.

PMID- 8544581
TI  - Preterm premature rupture of membranes.

PMID- 8544582
TI  - Preterm premature rupture of membranes.

PMID- 8544583
TI  - Preterm premature rupture of membranes.

PMID- 8544584
TI  - Preterm premature rupture of membranes.

PMID- 8544585
TI  - Heat exposure as a hazard to male fertility.

PMID- 8544586
TI  - Biocompatible membranes in acute renal failure.

PMID- 8544587
TI  - Strikes in French public transport and resistance to activated protein C.

PMID- 8544588
TI  - Airway obstruction in the Pierre Robin sequence.
AB  - Airway obstruction and feeding difficulties vary among patients with Pierre Robin
      sequence (PRS). Treatment is challenging and the appropriate management may not
      be readily identified, leading to delay in securing the airway. A retrospective
      review of 90 children with PRS was done to identify subgroups at a higher risk of
      developing severe airway obstruction using oxygen and apnea monitoring, sleep
      studies, and response to treatment. Patients with isolated PRS (group I, 27
      patients) and Stickler syndrome (group II, 32 patients) do not suffer from
      debilitating airway and feeding difficulties when compared to those with unique
      syndromes (group III, 16 patients) and recognized named syndromes (group IV, 15
      patients). Feeding difficulties were universal with the severity proportional to
      airway obstruction. Aggressive intervention should be considered early in group
      III and IV patients.

PMID- 8544589
TI  - Carotid body tumors: a review of 30 patients with 46 tumors.
AB  - Minimal morbidity occurs with resection of most carotid body tumors (CBT). With
      larger tumors significant injury to the cranial nerves has been reported. In
      order to assess the operative sequelae rate, 30 patients with CBT were reviewed.
      Sixteen patients either presented with bilateral carotid body tumors or had
      previously undergone a resection of the contralateral carotid body tumors, for a
      total carotid body tumor count of 46. Sixteen patients demonstrated a familial
      pattern while 14 were nonfamilial. Within the familial group, 14 of 16 presented
      with multiple paragangliomas as compared to 6 of 14 in the nonfamilial group.
      Tumor size ranged from 0.8 to 12 cm. Vascular replacement occurred in 2 of 20
      patients with tumors < 5.0 cm, compared with 5 of 9 with tumors > 5.0 cm. Four
      patients lost cranial nerves with the resection: superior laryngeal nerve (SLN),
      4; cranial nerve X, 1; cranial nerve XII, 1. Ten patients developed baroreceptor
      failure secondary to bilateral loss of carotid sinus function. First-bite pain
      occurred in 10 of 25 operative patients. Cranial nerve loss can be minimal with
      resection of carotid body tumors, however, baroreceptor failure and first-bite
      pain are postoperative sequelae that are often disregarded in the postoperative
      period.

PMID- 8544590
TI  - Atypical stromal cells in inflammatory nasal polyps: immunohistochemical and
      ultrastructural analysis in defining histogenesis.
AB  - The authors investigated 29 cases of sinonasal polyps with atypical stromal cells
      (ASC). The clinicopathologic features of these lesions were of benign
      inflammatory polyps except for the presence of ASC. Misinterpretation of these
      cells resulted in contributor diagnosis of sarcoma (rhabdomyosarcoma).
      Immunohistochemical study of the ASC demonstrated the presence of actin (smooth
      muscle and muscle specific), KP-1, and vimentin; no reactivity was seen with
      desmin, myoglobin, S-100 protein, or glial fibrillary acidic protein (GFAP).
      Unexpectedly, cytokeratin reactivity was identified in more than 75% of the cases
      analyzed. Ultrastructural analysis revealed that the ASC shared morphologic
      features in common with fibroblasts and smooth muscle cells. Based on the light
      microscopic, immunohistochemical, and ultrastructural findings, it was concluded
      that the ASC represent reactive myofibroblasts and not a neoplastic
      proliferation. Follow-up data supported this contention indicating the absence of
      an aggressive biological course. Misinterpretation as a malignant neoplasm might
      result in unwarranted and unnecessary therapeutic intervention.

PMID- 8544591
TI  - The use of positron emission tomography for early detection of recurrent head and
      neck squamous cell carcinoma in postradiotherapy patients.
AB  - Positron emission tomography (PET) has recently proved to be highly sensitive in
      detecting known extracranial head and neck squamous cell carcinomas when compared
      to computed tomography and magnetic resonance imaging (MRI). The ability of PET
      to detect early subclinical recurrent squamous cell malignancies in patients who
      received primary radiotherapy was evaluated. A new PET-MRI coregistration
      technique was used to determine precise anatomic tumor location, enabling
      directed biopsies to confirm the presence of malignancy, and to plan additional
      therapeutic strategies. Ten patients underwent PET evaluation with intravenous
      [18F]-fluorodeoxyglucose and received postradiotherapy MRI scans. In all cases,
      PET accurately detected the presence of recurrent disease despite negative or
      equivocal MRI scans and indeterminate clinical examinations. PET appears to be
      highly effective in detecting early recurrent head and neck squamous cell
      malignancies in postirradiated patients.

PMID- 8544592
TI  - Effect of local epinephrine on cutaneous bloodflow in the human neck.
AB  - The effectiveness of local anesthetics is improved by the addition of a
      vasoconstrictor which increases duration of action and decreases both systemic
      toxic reactions and local bleeding. Epinephrine, the standard drug for
      vasoconstriction, has some limitations due to potential dose-related cardiac and
      local toxic effects. The authors examined the minimal effective epinephrine
      concentration required for maximal cutaneous vasoconstriction in the human
      subject so as to limit potential dose-related side effects. In a randomized,
      double-blinded prospective study, 23 patients undergoing head and neck surgical
      procedures under general anesthesia were enrolled to quantify the effect of
      subdermal infiltration of 1% lidocaine with epinephrine at varying concentrations
      on local cutaneous bloodflow utilizing laser Doppler flowmetry. A comparison of
      the onset of vasoconstriction and magnitude of diminished bloodflow was made for
      several commonly used concentrations of epinephrine, with 1% lidocaine and normal
      saline serving as controls. There were no significant differences (P > .05)
      between epinephrine concentrations of 1:400,000, 1:200,000, 1:100,000, and
      1:50,000 when examining onset and magnitude of vasoconstriction.

PMID- 8544593
TI  - The effect of botulinum toxin type A injection on compound muscle action
      potential in an in vivo rat model.
AB  - Serial measurements were performed on the compound muscle action potential (CMAP)
      amplitude and the force generated by the rat lower hind limb flexors to
      investigate the time course of intramuscular injections of botulinum toxin type A
      (BOTOX). Thirty animals were used in this in vivo rat model. CMAP amplitude and
      muscle force were measured at predetermined intervals for 28 weeks. Compound
      muscle action potential amplitude and force declined markedly the first 5 to 7
      days after injection of BOTOX but recovered in a near linear manner. The response
      magnitude and recovery rate were dose-dependent. Recovery of CMAP amplitude
      preceded recovery of muscle force. No clear evidence of a systemic effect on the
      untreated leg or a concentration effect was found. CMAP amplitude may be useful
      in determining optimal timing of repeat injections in treating neuromuscular
      disorders.

PMID- 8544594
TI  - Flow cytometric analysis of primary and metastatic squamous cell carcinoma of the
      oral cavity and oropharynx.
AB  - A retrospective analysis of formalin-fixed, paraffin-embedded tissue from
      patients with histologically confirmed metastatic squamous cell carcinoma was
      performed using flow cytometry. Ninety-eight sets of specimens from previously
      untreated patients with an oral cavity or oropharyngeal tumor and a simultaneous
      cervical metastatic deposit were analyzed. Normal mucosa and cervical lymph nodes
      were processed identically and run as controls. All patients underwent surgical
      resection at Wilford Hall USAF Medical Center or The Eye and Ear Hospital of
      Pittsburgh between 1980 and 1986. The specimens from 94 patients were technically
      adequate for interpretation. Diploid histograms in both the primary and
      metastatic tumors were present in 49 (52%) of 94 patients. Aneuploid histograms
      in either the primary and metastatic tumors were noted in 45 (47%) of 94
      patients. In this group of 45 patients, the primary tumor and cervical metastasis
      were both aneuploid in 21 (46%), and aneuploid histograms occurred with equal
      incidence in either the primary or metastasis in the remaining 24 cases. No
      statistically significant prediction of survival could be made from any
      correlation with the histograms of either the primary or metastasis. The
      potential technical problems and limitations of flow cytometry in the
      determination of DNA content of formalin-fixed, paraffin-embedded tissue and the
      selection of patients with advanced disease warrant caution in the interpretation
      of results.

PMID- 8544595
TI  - Reconstruction of suboccipital craniectomy defects with hydroxyapatite cement: a
      preliminary report.
AB  - Hydroxyapatite cement, a new biomaterial presently under clinical investigation,
      has been demonstrated to have potentially wide application in cranial
      reconstruction. We describe our experience with this biologic bone cement in the
      reconstruction of suboccipital craniectomy defects in seven patients after
      vestibular schwannoma removal. With up to 2-year follow-up, cranial bone
      integrity has been reestablished in five patients. Dissolution of cement has
      occurred in dependent areas and appears to be technique related. Cranial bone
      contour appears dependent on the amount of cement used. The frequency of
      debilitating postoperative headache was reduced in these patients when compared
      to patients who had no reconstruction of the craniectomy defect. Reconstruction
      of the bony defect after suboccipital craniectomy with hydroxyapatite cement is
      not only useful to restore cranial contour, but also appears to reduce some of
      the functional deficits attributed to this surgical approach.

PMID- 8544596
TI  - Laryngopharyngoesophagectomy for advanced hypopharyngeal and esophageal squamous
      cell carcinoma: the Yale experience.
AB  - The 5-year survival rate for patients with hypopharyngeal squamous cell carcinoma
      invading the upper esophagus is below 25% regardless of therapy. Most patients
      with advanced disease--unable to eat or breathe--die within 18 months of
      diagnosis. Because these patients, on average, have a limited time to live,
      surgical treatment should aim to maximize the quality of remaining life.
      Essential to this goal are complete tumor removal and rapid return to oral
      feeding. Furthermore, short hospital stay and low perioperative morbidity are
      especially important in these patients. We performed total
      laryngopharyngoesophagectomy (LPE) with gastric transposition in 34 patients with
      hypopharyngeal and cervical esophageal squamous cell carcinoma. There has been
      one perioperative death (3%) and 1 temporary fistula (3%). No major mediastinal
      or intrathoracic complication occurred. On average, patients began oral feeding
      by postoperative day 10, with return to a full diet and discharge home within 16
      days, maximizing both quality and quantity of time remaining outside the
      hospital.

PMID- 8544597
TI  - Three-dimensional reconstruction of the feline larynx with serial histologic
      sections.
AB  - This paper reviews a new technique to develop high-resolution three-dimensional
      (3-D) images of the larynx using histological sections. Three-dimensional
      computer-reconstructed histological sections of the cat are used in this study to
      evaluate the recurrent laryngeal nerve (RLN) in its true anatomic course, with
      emphasis on its relationship to surrounding structures (laryngeal framework). A
      cat model was used because of specimen availability and technical ease of tissue
      preparation. Computer-reconstructed serial histologic sections add a new
      dimension to the study of laryngeal anatomy, laryngeal trauma, and growth
      patterns of laryngeal cancer. The technical aspects of three-dimensional
      reconstruction and future applications are discussed.

PMID- 8544598
TI  - Internal jugular vein thrombosis following functional neck dissection.
AB  - Twenty-five patients on whom 27 functional neck dissections were performed for
      upper aerodigestive tract squamous carcinoma were prospectively investigated to
      determine the frequency of venous thrombosis on the side of the neck dissection.
      Retrograde venography, performed within 1 month postoperatively, was used to
      determine the status of the internal jugular vein. Nineteen veins were patent at
      venography, but ipsilateral occlusion was demonstrated in 8. In 5 of the 8
      patients, venous thrombosis followed major wound sepsis or fistula formation. No
      causes for the remaining 3 cases of internal jugular vein thromboses were
      identified. Possible mechanisms for "spontaneous" internal jugular vein occlusion
      following functional neck dissection are endothelial trauma, reduction in venous
      flow during anesthesia, and the altered coagulability profile of some cancer
      patients. The finding that functional neck dissection does not always maintain
      patency of the internal jugular vein is especially important when surgical
      treatment to the opposite side of the neck is planned, as the surgeon may be
      faced with an unexpectedly complicated postoperative course.

PMID- 8544599
TI  - Nasal inflammation in patients with obstructive sleep apnea.
AB  - The purpose of this study was to determine whether nasal inflammation is present
      in patients with obstructive sleep apnea (OSA). The number of polymorphonuclear
      leukocytes (PMNs) and the concentrations of bradykinin and vasoactive intestinal
      peptide (VIP) were quantified in nasal lavage fluid of eight nonsmoking patients
      with OSA and in six matched controls before sleep and the next morning. The total
      number of cells and the percentage of PMNs was significantly higher in patients
      with OSA in comparison to controls before and after sleep (P < .05). Likewise,
      bradykinin and VIP concentrations were significantly higher in patients with OSA
      in comparison to controls before and after sleep (P < .05). These findings
      indicate that nasal inflammation is present in patients with OSA. We suggest that
      nasal inflammation plays a role in upper airway obstruction in OSA.

PMID- 8544600
TI  - Squamous cell carcinoma arising in inverted papilloma.
AB  - A retrospective review of all cases of inverted papilloma at the University of
      Michigan from 1975 to 1992 revealed 51 cases of inverted papilloma. Of these, 14
      (27%) had an associated squamous cell carcinoma (SCC). Eight (16%) were
      metachronous and 6 (11%) were synchronous. At a mean follow-up of 53 months, the
      disease-free survival of patients with carcinoma limited to the nasal cavity and
      paranasal sinuses was 57% (4/7) compared to 14% (1/7) of those patients
      presenting with disease extending beyond the nasal cavity and paranasal sinuses.
      The data also support the lateral rhinotomy approach with medial maxillectomy and
      ethmoidectomy as a minimum procedure followed by postoperative radiation therapy.
      The mean interval between the diagnosis of inverted papilloma and development of
      SCC was 63 months (range, 6 months to 13 years). Therefore, long-term follow-up
      with clinical examination and computed tomography (CT) scan is indicated for all
      patients with inverted papilloma.

PMID- 8544601
TI  - Hearing preservation in acoustic tumor surgery: results and prognostic factors.
AB  - A retrospective study was conducted to assess the hearing results in patients who
      underwent acoustic neuroma removal via the middle fossa approach. A statistical
      correlation of results with preoperative clinical and audiological data
      determined if any prognostic indicators could be associated with successful
      hearing preservation. Of 93 patients included in the study, useful hearing was
      preserved in 54 (58%), and hearing was preserved near preoperative levels in 42
      (45%). The potential for hearing preservation appeared to be inversely related to
      the size of the acoustic tumor, with hearing preserved in 39 (60%) of 65 patients
      with tumors less than or equal to 0.5 cm extension into the cerebellopontine
      angle. Preoperative hearing levels and electronystagmography seemed to have no
      prognostic value. However, auditory brainstem response showed that a wave V
      latency of less than 6.8 msec was associated with an increased chance of hearing
      preservation, and the presence of vertigo as a preoperative complaint appeared to
      be a good prognostic indicator of successful hearing preservation.

PMID- 8544602
TI  - Biochemical evidence of platelet-activating factor (PAF) in human middle ear
      effusions.
AB  - Platelet-activating factor (PAF) is one of the most potent biological lipid
      mediators. This is especially true in relation to inflammation. In order to
      characterize the biochemical features of otitis media with effusion, the authors
      characterized and determined the concentration of the PAF present in human middle
      ear effusions obtained from 23 patients with otitis media with effusion. Each
      sample of middle ear effusion was divided into two groups: serous (n = 12) and
      mucoid effusions (n = 11). The platelet-activating factor activity was found
      mainly in mucoid middle ear effusions, and the amounts of PAF were higher in
      mucoid type (3.55 +/- 1.19 ng/g, mean +/- standard deviation [SD]) than in the
      serous type (0.44 +/- 0.19 ng/g). Phospholipids obtained from the middle ear
      effusions contained a large amount of lyso-platelet-activating factor, the
      biologically inactive precursor or breakdown product of platelet-activating
      factor. Based on these findings, it is suggested that platelet-activating factor
      may play an important role as a mediator of the inflammatory responses in the
      pathogenesis of otitis media with effusion.

PMID- 8544603
TI  - Effects of endolymphatic duct occlusion on the structure and function of the
      endolymphatic sac in the adult guinea pig.
AB  - The endolymphatic sac (ELS) has been shown to respond rapidly to sudden
      disruptions in fluid balance such as labyrinthectomy or systemic administration
      of hyperosmolar agents. The present study was designed to determine the ELS
      response to slower changes in fluid dynamics by occluding the endolymphatic duct
      (ELD), thereby interrupting the longitudinal flow of endolymph to the ELS.
      Morphologic studies and autoradiographic techniques were used to evaluate the
      effects of ELD obstruction on the structure and function of the ELS after 48
      hours. There were no significant changes in cellular morphology and a slight
      decrease in the incorporation of radiolabeled glucose when compared with normal
      ELS cells. We conclude that it is rapid change in fluid balance that triggers the
      ELS response, which is not seen with disruption of longitudinal flow.

PMID- 8544604
TI  - The use of a laryngotracheal separation procedure in pediatric patients.
AB  - The objective of this study was to review experience, outcome, and satisfaction
      after a laryngotracheal separation (LTS) procedure in pediatric patients. Chart
      reviews and phone questionnaires were used. Factors reviewed included
      hospitalizations and infections prior to and after LTS, morbidity, and impact on
      quality of life. Twenty-one pediatric patients ranging in age from 8 to 172
      months underwent LTS. Follow-up time ranged from 1 to 49 months. Complications
      were minor. Eighty-eight percent of patients had fewer hospitalizations or were
      discharged for the first time after LTS. Number of pneumonias and suctioning
      frequency decreased, mobility increased in patients with prior tracheostomies,
      and care requirements decreased in 95% of patients. Parents reported satisfaction
      and improved quality of life. LTS is a low-risk, successful procedure which
      increases quality of life and decreases morbidity in pediatric patients with
      irreversible upper airway dysfunction.

PMID- 8544605
TI  - Combined transconjunctival and external approach for endoscopic orbital apex
      decompression in Graves' disease.

PMID- 8544606
TI  - Gore-Tex implants for the correction of thin lips.

PMID- 8544607
TI  - Midline osteotomy with lag screw stabilization for mandibular swing.

PMID- 8544608
TI  - Intraoperative audiometry.

PMID- 8544609
TI  - Fixation of the electrode cable during cochlear implantation: the split bridge
      technique.

PMID- 8544610
TI  - Reducing temporal lobe retraction with the middle fossa approach using a lumbar
      drain.

PMID- 8544611
TI  - Healthcare reform--lessons from the Canadian system.

PMID- 8544612
TI  - Airway control during percutaneous tracheotomy.

PMID- 8544613
TI  - Temporal bone findings in Alzheimer's disease.
AB  - Sensorineural hearing loss has been reported in Alzheimer's disease (AD) and a
      topographically specific pattern of degeneration in the central auditory system
      has been described. Although peripheral visual and olfactory systems have been
      extensively studied, there is no report of peripheral auditory system
      abnormalities in AD patients. Comparison of temporal bones from eight AD patients
      with those from eight non-AD controls revealed a significant difference in the
      percentage of remaining hair cells, peripheral processes, and spiral ganglion
      cells in the basal cochlear turn but no significant differences in the overall
      percentage between the two groups. Furthermore, special stains (thioflavin S and
      Bielschowsky's silver impregnation) of temporal bone nervous tissue from AD
      patients did not show neuritic plaques and neurofibrillary tangles. It is unclear
      whether the differences between the two groups in the basal portion of the
      cochlea are due to AD or some other process, such as presbycusis. However, lack
      of significant degeneration in other parts of the cochlea and absence of
      neurofibrillary tangles and neuritic plaques in all eight patients may suggest
      that the peripheral auditory system, unlike the peripheral visual and olfactory
      systems, is not involved in AD. A larger sample of AD patients is necessary to
      clarify the peripheral auditory system findings in the present study.

PMID- 8544614
TI  - Laser-assisted uvulopalatoplasty for obstructive sleep apnea.
AB  - Laser-assisted uvulopalatoplasty (LAUP) can reduce snoring by sequentially
      removing excessive vibratory tissue of the velopharynx. The procedure can be
      performed under local anesthesia in an office setting. Since the appearance of
      the soft palate is similar after both LAUP and uvulopalatopharyngoplasty, LAUP
      may also be efficacious in the management of obstructive sleep apnea syndrome
      (OSAS). LAUP was performed in 34 consecutive prospectively evaluated patients
      with OSAS. Of the 34 patients, 28 (82%) were male; the mean age was 53 years, and
      the mean body mass index was 31.1. In the study population of 13 patients who
      completed preoperative and postoperative sleep studies, the apnea index decreased
      from 19.4 to 4.2 (P = .006), the respiratory disturbance index (RDI) decreased
      from 31.2 to 15.7 (P = .092), and mean lowest oxyhemoglobin saturation increased
      from 82.3% to 85.0% (P = .581). The RDI fell to 10 or lower in 38.5% of patients
      and was reduced by at least 50% in 53.8% of the study group. Snoring was
      significantly reduced in 92.3% of patients (P < .001). These early results
      suggest that LAUP may be efficacious in the management of OSAS.

PMID- 8544615
TI  - Histopathology and CT analysis of partially resected middle turbinates.
AB  - Thirty-eight partial middle turbinate resections from 20 patients undergoing
      endoscopic sinus surgery were evaluated by histopathology of mucosa and bone and
      by computed tomography (CT) appearance prior to resection. Histopathologic
      analysis revealed not only mucosal inflammation but also chronic osteitis of the
      bone in all patients with sinus disease. The preoperative CT was accurate in
      predicting turbinate osteitis when the scans displayed advanced grades III and IV
      disease. These findings suggest that in advanced disease, conservative partial
      middle turbinate resections may be necessary to remove chronically infected bone
      from the osteomeatal complex. Because it is unsafe to remove all of the middle
      turbinate, consideration should also be given to long-term antibiotic therapy to
      treat the osteitis found in advanced disease.

PMID- 8544616
TI  - Endonasal endoscopic surgery for rhinogen intraorbital abscess: a report of six
      cases.
AB  - Intraorbital abscess is a serious complication of sinusitis with the danger of
      permanent loss of vision and even the danger of life-threatening progress. The
      recommended surgical procedure in the literature for drainage of an intraorbital
      abscess is the external approach. We report on successful functional endonasal
      endoscopic surgery in a series of six sequential cases with intraorbital
      abscesses following sinusitis. The main advantages of this approach are the
      simultaneous treatment of causative disorders with surgery following the
      pathogenic route of the abscess formation and lack of trauma to further
      structures. The endoscope with 25- or 70-degree angled axis of vision enables the
      surgeon to explore and drain the abscess cavity, which often is located behind
      the bulbus, with minimal trauma. For the trained surgeon the field of vision is
      favorable as compared with the external approach when the abscess is located
      right in the axis of vision and one has to cut through healthy tissue and the
      intact skin, which, especially in children, can lead to long-lasting visible
      scars.

PMID- 8544617
TI  - The tracheostoma in relation to prosthetic voice rehabilitation.

PMID- 8544618
TI  - J-shaped, conchal excision with rotation advancement for closure of large,
      auricular wedge defects.

PMID- 8544619
TI  - Medication names.

PMID- 8544620
TI  - Successful therapy for psychological aphonia.

PMID- 8544621
TI  - The extended lateral arm free flap for head and neck reconstruction: the Yale
      experience.
AB  - The lateral arm free flap (LAFF) has been chosen by some head and neck
      reconstructive microsurgeons to be their fasciocutaneous free flap of choice. The
      qualities of this flap have been suggested to include its consistent vascular
      anatomy, its thin and pliable nature, and its reinnervation capabilities, as well
      as its low donor site morbidity and ease of closure. During the past year we have
      performed 14 head and neck reconstructions using the extended LAFF (ELAFF). We
      present our indications for its use and review its shortcomings. Although the
      ELAFF does have its limitations, including variability in its flap thickness and
      donor vessel size, it unquestionably is an important flap in head and neck
      reconstruction and is our flap of choice for soft tissue reconstruction.

PMID- 8544622
TI  - Value of videostroboscopic parameters in differentiating true vocal fold cysts
      from polyps.
AB  - Differentiating between benign true vocal fold (TVF) cysts, polyps, and nodules
      on the basis of their gross appearance would be advantageous in determining the
      need for surgical therapy. A retrospective study of 32 patients covering 31
      months was done to assess the ability to differentiate these lesions on the basis
      of stroboscopic parameters. Stroboscopic examinations were evaluated for
      symmetry, amplitude, periodicity, mucosal wave, and closure. Preoperative
      diagnoses were validated with operative and histologic confirmation. Mucosal wave
      was absent or diminished in 100% of TVF cysts and present or increased in 80% of
      TVF polyps (P < .05). Thirty-one percent of original histopathologic diagnoses
      were modified after pertinent clinical information was provided to the
      pathologist. Therefore, stroboscopic evaluation of mucosal wave is helpful in
      preoperative differentiation of TVF cysts and polyps, and providing clinical
      information to the pathologist is critical for useful histologic information.

PMID- 8544623
TI  - Outcome of pyriform sinus cancer: a retrospective institutional review.
AB  - Pyriform sinus cancer remains one of the most lethal of human diseases.
      Regardless of approach attempted significant enhancement of survival has not been
      realized. In this study a retrospective single institutional review of all
      patients diagnosed with pyriform sinus cancer during the 1980s was conducted. The
      results in 93 patients show an overall determinant 5-year survival of 14.3%. Of
      patients undergoing surgery, median determinant survival was 37 months and 5-year
      survival was 34.6%. In resectable patients treated with radiation with or without
      chemotherapy, median determinant survival was 13 months with 5-year survival of
      7.1% (P < .01). Surgical salvage was attempted in 8 patients without success. In
      conclusion, due to the apparent survival advantage for surgical patients, the low
      rate of surgical salvage, and the relatively low rate of organ preservation in
      prospective trials, pyriform sinus cancer is a poor site for organ preservation.
      Surgery followed by radiation therapy should remain the standard of care for
      pyriform sinus cancer.

PMID- 8544624
TI  - "Decadose" effects of cisplatin on squamous cell carcinoma of the upper
      aerodigestive tract. I. Histoculture experiments.
AB  - There is substantial laboratory and clinical evidence that solid tumors rapidly
      acquire cellular resistance to cisplatin. Experiments with human carcinoma cell
      lines and clonogenic assays indicate that resistance is usually mild to moderate
      and can be circumvented with higher concentrations of drug. The purpose of this
      investigation was to test this hypothesis with a histoculture assay of human
      upper aerodigestive tract (UADT) carcinomas. Using a sponge-gel supported
      histoculture, 43 tumor specimens from patients with squamous cell carcinoma (SCC)
      of the UADT were grown and exposed to cisplatin. Growth inhibition by the drug,
      in concentrations equivalent to peak therapeutic doses (1.5 micrograms/mL) and
      concentrations 10 and 25 times greater (15 and 37.5 micrograms/mL), were measured
      in specimens from patients with previously untreated and recurrent lesions. In
      vitro, the overall rate of sensitivity of the tumor samples to cisplatin
      concentrations of 1.5, 15, and 37.5 micrograms/mL were 22%, 62%, and 83%,
      respectively. In patients with previously untreated disease, the respective rates
      were 25.9%, 63.3%, and 79.3%, as compared with 10.0%, 55.6%, and 85.6%,
      respectively, for patients with recurrent disease. The response difference
      between cisplatin concentrations of 1.5 and 15 micrograms/mL was statistically
      significant. The "decadose" effect of cisplatin on growth inhibition was 2.44
      fold for untreated lesions and 5.56-fold for recurrent tumors. The results
      indicate that resistance to standard doses of cisplatin by SCC of the UADT can be
      substantially overcome with a decadose (standard dose x 10) increase and is more
      pronounced in tumors from patients with recurrent disease. Progress toward
      improving survival of patients may be possible by incorporating decadose
      cisplatin therapy into a multimodality treatment plan.

PMID- 8544625
TI  - "Decadose" effects of cisplatin on squamous cell carcinoma of the upper
      aerodigestive tract. II. Clinical studies.
AB  - There is evidence that solid tumors rapidly acquire cellular resistance to
      cisplatin. This resistance is usually mild to moderate and could be circumvented
      with higher concentrations of drug exposure if ancillary methods were available
      to avoid systemic cytotoxicity. The purpose of this study was to determine
      whether a tenfold increase in dose (decadose) would overcome cisplatin
      resistance. In a clinical trial, response effects of cisplatin at dose
      intensities ranging from 32.5 to 200 mg/m2 per week, which were delivered by
      highly selective intra-arterial infusions with a simultaneously administered
      intravenous neutralizing agent, were measured in 31 patients with squamous cell
      carcinoma (SCC) of the upper aerodigestive tract (UADT). The overall response
      rate (complete response [CR] and partial response [PR] to cisplatin therapy at
      dose intensity intervals of 0 to 74, 75 to 149, and 150 to 200 mg/m2 per week
      were 45.5%, 72.7%, and 100%, respectively. The average received dose intensities
      for nonresponders and responders (CR and PR) were 57.8 and 120.7 mg/m2 per week,
      respectively (P = .031). The results indicate that resistance to standard doses
      of cisplatin by SCC of the UADT, both previously untreated and recurrent, can be
      substantially overcome with "decadose" cisplatin therapy. Progress toward
      improving survival of patients with head and neck cancer, and possibly other site
      specific malignancies, may be achieved by incorporating decadose cisplatin
      therapy into a multimodality treatment plan.

PMID- 8544626
TI  - Bilateral sensorineural hearing loss associated with the point mutation in
      mitochondrial genome.
AB  - Mitochondrial DNA (mtDNA) mutation associated with sensorineural hearing loss
      (SNHL) has previously been described in MELAS (mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes) and in aminoglycoside
      induced deafness. The authors of this study report three cases of SNHL associated
      with mtDNA mutation (3243A-->G). They examined the clinical features of this type
      of SNHL by audiologic studies and examined the mtDNA mutation by the polymerase
      chain reaction technique. In the three cases described, the SNHL had an adult
      onset and was bilateral and symmetrical. All patients had adult-onset diabetes
      mellitus. Audiologic studies revealed that the SNHL in all patients derived from
      the cochlea rather than from retrocochlear sites. It is presumed that mtDNA
      mutation results in mitochondrial dysfunction in cochlear tissues (i.e., hair
      cells and stria vascularis) and in neurons of the auditory pathway. Genetic
      analysis of mtDNA offers new insight into the diagnosis and treatment of SNHL.

PMID- 8544627
TI  - Auditory findings in patients with maternally inherited diabetes and deafness
      harboring a point mutation in the mitochondrial transfer RNA(Leu) (UUR) gene.
AB  - Five patients with sensorineural hearing loss, who harbored a point mutation in
      the mitochondrial transfer RNA (tRNA) gene tRNA(Leu) (UUR), from five unrelated
      family pedigrees were examined. In these families diabetes and deafness were
      maternally inherited. Bilateral hearing was more severely impaired at higher
      frequencies. Audiometric test results revealed that hearing loss involved the
      cochlea. Hearing gradually deteriorated; the progression rate ranged from 1.5 to
      7.9 dB per year. Proportion of mutant mitochondrial DNAs (mtDNAs) in the
      leukocytes was not related to the rate or degree of hearing loss, although
      hearing loss appeared at a younger age in patients with higher heteroplasmy. We
      speculate that after the proportion of damaged mtDNAs, mostly as a result of
      mutation, exceeds the expression threshold for deficiencies in mitochondrial
      protein synthesis and oxygen consumption, a drop in adenosine triphosphate level
      could lead to an imbalance of ion concentration, resulting in cell death in the
      cochlea.

PMID- 8544628
TI  - Brainstem auditory evoked potentials in patients with ischemic heart disease.
AB  - The authors of this study used the method of increased stimulus rate on brainstem
      auditory evoked potentials (BAEPs) in 30 patients with ischemic heart disease
      (IHD) and in an equal number of healthy age-matched control subjects. The BAEPs
      were recorded using 100- to 3000-Hz alternating polarity clicks at a rate of 22.6
      per second. Measurements included the absolute latencies of waves I through V,
      the interpeak latencies I-III, III-V, and I-V, and the peak amplitudes of peaks
      I, III, and V. The measured absolute latencies and interpeak latencies were found
      to be significantly increased, and the peak amplitudes were found to be
      diminished. The audiometric tests revealed no significant hearing loss in IHD
      patients. This study is the first to demonstrate prolongation of BAEPs in IHD
      patients. BAEP recording may become an additional noninvasive tool for detecting
      IHD patients with impaired microcirculation.

PMID- 8544629
TI  - Surgical treatment of acoustic neuroma (vestibular schwannoma) in the United
      States: report from the Acoustic Neuroma Registry.
AB  - In 1989, the Acoustic Neuroma Association established a multisurgeon, multi
      institutional registry to collect data related to the treatment of patients with
      acoustic neuroma. This report analyzes information from the 1579 surgically
      treated patients who were entered in the registry between January 1, 1989, and
      February 28, 1994.

PMID- 8544630
TI  - The oculocephalic response in the evaluation of the dizzy patient.
AB  - The oculocephalic response (OCR) is a simple office maneuver that assesses the
      vestibulo-ocular reflex (VOR). An abnormal response is manifested clinically as
      refixation saccades following a rapid horizontal head movement. Because little
      attention has been given to the OCR in the literature, a prospective study was
      undertaken with 112 consecutive patients who presented with dizziness and
      underwent OCR testing followed by caloric evaluation. Agreement was good between
      the OCR and caloric evaluation (kappa = 0.44). Specificity was quite high (97%);
      sensitivity was found to be less (39%). Positive (68%) and negative (90%)
      predictive values of the OCR illustrate that the clinician can often anticipate
      the results of caloric testing based on this response. This easily performed test
      of the VOR is a useful tool in the evaluation of the dizzy patient.

PMID- 8544631
TI  - Mastoid surgery in the only hearing ear.
AB  - Every otologic procedure carries the risk of damage to the inner ear. On the
      other hand, cholesteatoma and uncontrolled tubotympanic disease can lead to
      partial or total sensorineural loss, as well as intracranial complications. Our
      experience of the surgical management of eight patients with an only hearing ear
      is presented. There were no dead ears in this series and no significant worsening
      of inner ear function. The air conduction pure-tone average was worse in two
      patients without change in bone conduction. Of the eight patients, six wear a
      hearing aid with success and two patients manage without an aid. The present
      small series confirms that patients at risk of anacusis from cholesteatoma or
      chronic suppurative otitis media can be offered, in experienced tertiary referral
      units, a safe method of stabilizing the ear and preserving useful hearing.

PMID- 8544632
TI  - The effect of tympanic membrane perforation size on umbo velocity in the rat.
AB  - The tympanic membrane (TM) in adult rats was surgically exposed and laser
      interferometry was used to measure TM velocity at the umbo for frequencies
      between 1.0 and 40.0 kHz. Velocity measures were obtained for five conditions: TM
      intact, and four progressively larger holes cut into the posterior region of the
      membrane. Photomicrographs of each condition were used to calculate the
      percentage of pars tensa lost to the perforation. The relation between TM
      velocity and stimulus sound pressure level (SPL) was also examined for each of
      the conditions. The results revealed a systematic loss in low-frequency velocity
      as perforation size increased. These observations were consistent with clinical
      reports of low-frequency hearing loss in the perforated human TM. The rat appears
      to be a successful model for studying this form of conductive pathology.

PMID- 8544633
TI  - Ambulatory tonsillectomy and adenoidectomy.
AB  - The performance of tonsillectomy and adenoidectomy in an ambulatory setting is
      controversial. However, most current studies show that with adequate criteria for
      patient selection and careful postoperative observation, these procedures can be
      safely done as outpatient surgery. This study was undertaken to reassess the
      safety of outpatient tonsillectomy and adenoidectomy surgery and to reevaluate
      the current recommendations for postoperative care. A prospective study was
      undertaken to relate the incidence of significant complications, including
      hemorrhage, protracted emesis, and fever, to each postoperative hour. The study
      included 534 pediatric patients (age 14 or less) undergoing tonsillectomy with or
      without adenoidectomy. All 534 patients were observed for 5 postoperative hours,
      and 175 of the 534 patients were observed for 6 postoperative hours. To assess
      complications occurring in the first postoperative week, all attending surgeons
      involved in this study were asked to anonymously report the occurrence of
      hemorrhage, protracted emesis, and/or fever from the time of discharge through
      the seventh postoperative day. In this study, no complications were encountered
      during the fifth or sixth postoperative hours. These results indicate that it is
      both safe and appropriate to perform tonsil and adenoid surgery in the ambulatory
      setting. Furthermore, the current recommendation that patients remain under
      postoperative recovery room observation for 6 hours appears to be excessive. This
      observation period may be safely reduced to 4 hours.

PMID- 8544634
TI  - Tracheal neovascularization: a method involving mobilization of a complete
      tracheal neovascularized segment using a sternohyoid muscle flap.
AB  - Tracheal segmental free grafts always tend to undergo necrosis with consequent
      occlusion of the airway. Revascularized grafts are impossible to carry out, since
      the trachea is devoid of a major vascular pedicle that would permit microvascular
      reconstruction. On the other hand, neovascularized grafts carry a potential for
      success but have not been sufficiently studied. Neovascularization of a six-ring
      circumferential tracheal segment (CTS) was studied in dogs using a sternohyoid
      muscle (SM) flap. Three different procedures were carried out. In group 1 the six
      ring CTS was inside a free graft. In group 2 the SM was freed from its proximal
      connection and rotated to wrap a corresponding six-ring CTS; it was then sutured
      and left in place for 21 days. After this period it was again approached, and the
      six-ring CTS was sectioned and sutured back in place, leaving the distally
      pedicled SM untouched. In group 3 an identical procedure was carried out, but the
      SM flap was left with a proximally rather than a distally based flap. All
      surviving animals were followed up for at least 1 year, and the results were
      analyzed by clinical and tracheoscopic observations and by macroscopic and
      microscopic studies after the animals were killed. All animals in group 1 died
      within 18 days; the studies showed necrosis and occlusion of the CTS. In groups 2
      and 3 there was no degenerative change of the CTS, whose aspect was close to
      normal on macroscopic and microscopic examination. We conclude that the free CTS
      graft is totally inviable. In contrast, neovascularization of the CTS occurs when
      the segment is first wrapped around with an SM flap. This ensures CTS viability
      and opens new perspectives for homotransplantation.

PMID- 8544635
TI  - The swallowing side effects of botulinum toxin type A injection in spasmodic
      dysphonia.
AB  - Botulinum toxin type A (BOTOX) injection of the thyroarytenoid muscle is used to
      control speech symptoms in patients with adductor spasmodic dysphonia. Transient
      difficulty in swallowing liquids is a common treatment side effect. Laryngeal
      movement durations were measured during swallowing in 13 adductor spasmodic
      dysphonia patients undergoing treatment and in 6 normal control subjects in order
      to determine the following: 1. whether, prior to the injection, laryngeal
      movement durations were longer in the spasmodic dysphonia patients than in the
      control subjects; 2. whether movement durations increased following the
      injections; 3. whether preinjection swallowing difficulties related to
      postinjection swallowing measurements and postinjection patient reports of
      swallowing problems. A piezoelectric movement transducer was shown to be accurate
      for noninvasive measurement of laryngeal movement duration in relation to muscle
      onset and offset for hyoid elevation and relaxation. Before botulinum toxin type
      A injection, no significant differences in swallowing duration were found between
      the patient and control groups. Four patients with swallowing complaints prior to
      injection had longer laryngeal movement durations than the other spasmodic
      dysphonia patients and the control subjects. Following injection, laryngeal
      movement durations increased in the patients with spasmodic dysphonia, and eight
      patients reported dysphagia for an average of 2 weeks. Relationships were found
      between the patients' initial reports of swallowing problems and increased
      laryngeal movement durations before and after botulinum toxin type A injection.
      Those patients initially reporting swallowing difficulties had severe dysphagia
      for 2 weeks after the injection. Patient reports of dysphagia prior to injection
      may indicate a greater likelihood of significant dysphagia following
      thyroarytenoid injection with botulinum toxin type A.

PMID- 8544636
TI  - Vocal capacities in esophageal and tracheoesophageal speakers.
AB  - The present study investigated the vocal capacities of adult men who had
      undergone total laryngectomy. Esophageal (N = 10) and tracheoesophageal (N = 10)
      speakers were compared for the parameters maximum phonation time (MPT), maximum
      number of syllables that could be spoken on one air intake (SYLLS), dynamic range
      (DYN), frequency range (FREQ), and maximum intensity level (MIL). Statistical
      analyses yielded significant between-group differences for the parameters MPT,
      SYLLS, and MIL but not for DYN and FREQ. Thus, although the groups did not differ
      with respect to range of intensity and frequency measures, maximum performance on
      the durational and intensity measures was always less for the esophageal speakers
      than for the tracheoesophageal speakers. Pearson's product-moment correlations
      among these parameters were remarkably different for esophageal and
      tracheoesophageal subjects, suggesting that phonatory and aerodynamic factors
      interact differently in the two groups.

PMID- 8544637
TI  - Choanal atresia: a new anatomic classification and clinical management
      applications.
AB  - The anatomic classification of choanal atresia is commonly quoted as 90% bony and
      10% membranous. This incidence is from a review by Fraser in 1910 of 115 cases,
      "many of which were insufficiently described." We have reviewed 47 computed
      tomography scans of choanal atresia from the literature and 16 from our clinical
      experience, and classified the anatomy as bony, mixed bony-membranous, or pure
      membranous. Our results reveal a combined incidence of 18 (29%) pure bony, 45
      (71%) mixed bony-membranous, and no pure membranous atresia. We propose a new
      classification of choanal atresia to include bony, mixed, and membranous to
      accurately reflect the anatomic abnormalities. Our series of 11 patients
      undergoing transnasal microsurgical repair, a critical review of the literature,
      and the implications of the anatomic classification on the choice of surgical
      procedure are presented.

PMID- 8544638
TI  - Lasers in gynecology: why pragmatic surgeons have not abandoned this valuable
      technology.

PMID- 8544639
TI  - Hepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy
      of viral hepatitis.
AB  - The use of nucleoside analogues as antiviral agents is expanding. For most
      nucleoside analogues, intracellular phosphorylation is the major prerequisite for
      activity. Antiviral activity may be limited by poor uptake, absence of
      appropriate activating enzymes, catabolism, and competition from endogenous
      nucleotides. Appreciation of these factors, which are species-, tissue- and cell
      specific is important in the understanding of the pharmacology and toxicology of
      nucleoside analogues. The use of nucleoside analogues against the agents of viral
      hepatitis is inherently problematic for many reasons including active hepatic
      nucleoside catabolism, probable absence of virus-specific activating enzymes,
      competition from endogenous nucleotides synthesised de novo or derived from RNA
      turnover, and factors related to mitochondrial toxicity. Despite these drawbacks,
      some nucleoside analogues have been found efficacious against hepatitis B virus
      and it is likely that as knowledge of their mechanism of action accumulates,
      their efficacy can be improved both by rational drug design and by use in
      combination with other drugs, including interferon.

PMID- 8544640
TI  - Clearance of serum hepatitis C virus RNA after interferon therapy in relation to
      virus genotype.
AB  - The effect of recombinant interferon-alfa on serum HCV RNA levels in Japanese
      patients with chronic hepatitis C was investigated. At 24 weeks of treatment, 41
      (32.5%) of 126 patients lost HCV RNA from serum, and aminotransferases were
      normalized in 31 (75.6%) of these 41 cases. HCV genotypes were categorized into
      four types (Type I, II, III, IV); the frequencies among the patients were: Type
      I: 0%, Type II: 70.6%, Type III: 20.6%, and Type IV: 6.3%. At the end of the 24
      week treatment, HCV RNA levels were remarkably decreased in Type III patients and
      became undetectable in 18 (69.2%) of 26. In contrast, only 18 (20.2%) of 89
      patients with Type II and two of eight with Type IV lost HCV RNA from sera. The
      relation between HCV genotype (Type III) and response to IFN therapy was also
      confirmed using a logistic regression model. HCV genotype seems to be an
      important factor in determining the response to IFN in patients with chronic
      hepatitis C.

PMID- 8544641
TI  - Hepatocyte and Kupffer cell function after liver transplantation in the rat--in
      vivo evaluation with dynamic scintigraphy.
AB  - In vivo physiological measurements of hepatocyte and Kupffer cell function after
      liver transplantation are desirable. Orthotopic liver transplantation was
      performed in 54 rats. Hepatocyte and Kupffer cell function were measured with
      dynamic liver scintigraphy. Hepatic clearance of 99mTc-Nanocoll (%/min), an
      albumin colloid phagocytosed by the Kupffer cells, was used to evaluate Kupffer
      cell function. Hepatic clearance of 99mTc-IODIDA (%/min), an imino-diacetic-acid
      taken up and secreted by the hepatocytes, was used to evaluate the hepatocyte
      function. Hepatic clearance in control rats was 27 +/- 2%/min for Nanocoll and 30
      +/- 3 %/min for IODIDA. After syngenic liver transplantation, without rejection,
      there was a rise in Nanocoll clearance (34 +/- 2 %/min p < 0.01) after 3 weeks,
      but no change in IODIDA clearance (32 +/- 3 %/min N.S.). After syngenic liver
      transplantation with preservation time prolonged to 16 h, there were no changes
      in IODIDA or Nanocoll clearance 1 day after transplantation. Both IODIDA (11 +/-
      2 %/min) and Nanocoll clearance (22 +/- 2 %/min) were decreased (p < 0.001)
      during rejection after allogenic transplantation. An in vivo method of measuring
      the hepatocyte and Kupffer cell function in the transplanted liver is described.
      Kupffer cell function was increased after syngenic liver transplantation. Kupffer
      cell and hepatocyte function were decreased during rejection. Dynamic liver
      scintigraphy seems a suitable procedure for examining liver injury after liver
      transplantation in the experimental setting.

PMID- 8544642
TI  - Primary biliary cirrhosis: lung involvement.
AB  - Sub-clinical lung impairment, mostly represented by a reduced diffusion of
      alveolar gases, is a recognised complication of advanced primary biliary
      cirrhosis. The aim of the study was to evaluate the prevalence and type of
      pulmonary involvement in primary biliary cirrhosis and the relationship between
      lung function abnormalities and selected epidemiological and clinical variables.
      Sixty-one patients with different stages of primary biliary cirrhosis
      consecutively seen in our outpatient clinic were evaluated. The advancement of
      primary biliary cirrhosis was characterised by the histological stage, the
      presence of signs of portal hypertension and the Mayo Risk Score: a Cox
      regression model using serum bilirubin and albumin levels, prothrombin time, age
      and degree of oedema as selected variables. We measured static and dynamic lung
      volumes, by means of a spirometer, and diffusing capacity for carbon monoxide.
      Rheumatological disorders were evaluated by an independent rheumatologist. No
      patient complained of respiratory symptoms. Airway obstruction was present in one
      patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did
      not find any significant relationship between diffusing capacity and smoking
      habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced
      diffusion capacity showed a significant correlation with the presence of complete
      or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti
      centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently
      impaired in patients with primary biliary cirrhosis, usually in the absence of
      clinical manifestations. These alterations mostly affect patients with
      concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544643
TI  - The measure of life-time alcohol consumption in patients with cirrhosis:
      reproducibility and clinical relevance.
AB  - Our aims were to design a reproducible method of measuring life-time alcohol
      consumption in patients with cirrhosis, and to assess the risk of liver
      decompensation associated with alcohol intake using a case-control design and a
      multivariate analysis. We studied 439 patients ("cases") with decompensated
      cirrhosis, and 233 with compensated cirrhosis ("controls"). Mean life-time daily
      amount and duration of alcohol intake were measured by a standardized
      questionnaire, whose reproducibility, assessed by interviewing 75 relatives, was
      70% for daily alcohol intake and 84% for duration of intake. Better
      reproducibility was found by re-interviewing patients at discharge from hospital.
      Daily alcohol intake was significantly higher in males, younger patients and
      patients with liver decompensation. After stratification according to the average
      life-time daily alcohol intake, we found a significant increase in the risk of
      liver decompensation from 125 g ethanol intake per day onwards. No association
      was found between duration of alcohol intake and risk of liver decompensation. We
      conclude that alcohol intake can be reliably and reproducibly measured: in
      patients with cirrhosis, increased alcohol intake is associated with increased
      risk of liver decompensation, with a significant dose-effect above a daily intake
      of 125 g ethanol.

PMID- 8544644
TI  - Hepatitis C virus infection in Italian intravenous drug users: epidemiological
      and clinical aspects.
AB  - The epidemological and clinical features of hepatitis C virus infection have been
      evaluated in a cohort of 227 intravenous drug users enrolled at a drug dependence
      treatment center in the Veneto area in 1992-1993 and followed periodically.
      Hepatitis C virus infection was detected using second-generation anti-HCV ELISA
      in 171 (75%) subjects at enrollment. Anti-HCV seropositivity correlated with: a)
      the duration of drug abuse: 91% of intravenous drug users injecting for more than
      8 years were seropositive as compared to 40% of those with a history of abuse
      lasting 4 years or less, p < 0.001; b) sharing of injection equipment: 85% anti
      HCV positive intravenous drug users had shared at some time as compared to 64%
      seronegative subjects, p < 0.001; c) seropositivity for immunodeficiency virus
      infection: 25% anti-HCV positive intravenous drug users were coinfected as
      compared to 3.5% anti-HCV negative, p < 0.001; d) markers of ongoing (two cases)
      or previous hepatitis B virus infection were detected in 62% of anti-HCV positive
      but in 21% of anti-HCV negative cases, p < 0.01. Two initially anti-HCV negative
      intravenous drug users seroconverted during follow up giving an incidence rate of
      hepatitis C virus infection of 6.2 per 100 person-years. During the survey
      abnormal alanine aminotransferase levels were detected in 75% anti-HCV positive
      but in 24% anti-HCV negative cases (p < 0.001), with significantly higher levels
      in the former. These findings suggest that the circulation of hepatitis C virus
      among intravenous drug users has been decreasing in recent years, although new
      infections still occur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544645
TI  - Manifestation late in life of idiopathic adulthood ductopenia.
AB  - Idiopathic adulthood ductopenia is a chronic cholestasic liver disease of unknown
      etiology characterized by the loss of interlobular bile ducts. We describe three
      patients who fulfilled the diagnostic criteria of idiopathic adulthood
      ductopenia, but differed from the cases reported so far in late manifestation of
      the disease and a benign clinical course despite histologic evidence of ongoing
      cholangitis. Treatment with ursodeoxycholic acid in one patient resulted in
      improvement of biochemical markers of cholestasis, suggesting that chronic
      cholestasis in idiopathic adulthood ductopenia can be influenced beneficially.

PMID- 8544646
TI  - The arterial ketone body ratio and serum alpha-fetoprotein level in patients with
      acute hepatic failure.
AB  - Hepatocyte regeneration is essential for recovery in acute hepatic failure,
      although it requires a large amount of energy. The ratio of acetoacetate to beta
      hydroxybutyrate in arterial blood has been reported to reflect the cellular
      energy charge of hepatocytes, and we proposed that the recovery of the ratio in
      the early days of acute hepatic failure is essential for survival. However, there
      is no report on any marker of regeneration to confirm this hypothesis. In this
      study, we have assessed this ratio and the serum alpha-fetoprotein level
      sequentially in 26 patients with acute hepatic failure. Ten patients recovered
      and 16 died. The arterial blood ketone body ratio 3 days after the onset of
      hepatic encephalopathy of grade II or more was below 0.6 in 15 of the 16
      nonsurvivors, whereas that in the 10 survivors was above 0.6. There was a
      positive correlation between the arterial blood ketone body ratio and the maximal
      concentration of alpha-fetoprotein (r = 0.465, p < 0.02 by Student's t-test).
      These data indicate that the arterial blood ketone body ratio is a marker for the
      capacity of the liver to regenerate and for the prognosis in patients with acute
      hepatic failure: effective hepatocyte regeneration may be impossible if these
      metabolic changes in acute hepatic failure impair the hepatocyte energy charge
      severely.

PMID- 8544647
TI  - Fast imaging MR assessment of ureterohydronephrosis during pregnancy.
AB  - PURPOSE: to assess the value of the fast imaging sequence called RARE-MR
      Urography (RMU) for the diagnosis of pathologic ureterohydronephrosis during
      pregnancy. MATERIALS AND METHODS: 15 pregnant women with an acute flank pain were
      examined with RMU. Results were compared with those of ultrasonography (US), X
      rays, and the evolution of symptoms. RESULTS: the accuracy of RMU in the
      detection of urinary tract dilatation and the localization of the level of
      obstruction was excellent (100%). The determination of the type of obstruction,
      intrinsic vs. extrinsic, was always exact. RMU alone cannot specify the exact
      nature of the intrinsic obstruction. Ultrasonography gave less sensitive
      information in terms of level (60%) and type of obstruction (53%). CONCLUSION:
      RMU is able to differentiate a physiological from a pathologic
      ureterohydronephrosis during pregnancy. It could be considered as a procedure of
      choice for special cases when US failed to establish this differential diagnosis.

PMID- 8544648
TI  - Sequential MR signal change of the thrombus in the false lumen of thrombosed
      aortic dissection.
AB  - The evolution of thrombus in the false lumen was investigated in 14 patients with
      thrombosed aortic dissection, by reviewing the findings acquired at a total of 21
      magnetic resonance imaging (MRI) examinations performed between 2 and 146 days
      after the onset. On electrocardiographic gated 1.5-Tesla MRI, T1-(TR/TE = 860 +/-
      190 ms/17-40 ms) and T2-(TR/TE = 1620 +/- 240 ms/70-80 ms) weighted spin echo and
      gradient echo images were obtained, and the signal intensity of the thrombus on
      these images was evaluated independently by two observers. The density of the
      thrombus was also evaluated using computed tomography (CT) images obtained at a
      total of 54 examinations. On both T1- and T2-weighted images, the thrombus showed
      signal iso- or hypointensity compared to that of skeletal muscle during the first
      several days after the onset and, thereafter, showed signal intensity similar to
      that of fat tissue. It is suggested that the low signal intensity of the thrombus
      observed during the initial period after the onset was caused by the presence of
      deoxyhemoglobin and the high intensity observed thereafter was caused by
      methemoglobin. Focal discrepancy of the signal intensities within two parts of
      the lumen on spin echo images was observed in 7 patients, and a low-intensity
      layer on the surface of the thrombus inside the false lumen was observed on
      gradient echo images in 5 of these 7 patients. This characteristic MR signal
      change of the thrombus in the false lumen of thrombosed aortic dissection
      provides useful information concerning the age of the thrombus and in the
      differential diagnosis of the thrombus from a mural thrombus of aortic aneurysm.

PMID- 8544649
TI  - Imaging of the apparent diffusion coefficient for the evaluation of cerebral
      metabolic recovery after cardiac arrest.
AB  - The apparent diffusion coefficient (ADC) of water is a sensitive indicator of
      water and ion homeostasis of brain. Resuscitation of the brain after cardiac
      arrest, the most frequent reason for global cerebral ischemia under clinical
      conditions, depends critically on the reversal of disturbances of water and ion
      homeostasis. We, therefore, investigated whether ADC imaging can be used to
      monitor the development and reversal of ischemic brain injury during and after
      cardiac arrest. Ten adult mongrel normothermic cats were anesthetized with
      alfentanil and midazolam, immobilized with pancuronium, and mechanically
      ventilated with O2/N2O. Arterial, left ventricular, central venous, and
      intracranial pressures were monitored throughout the experiment. Magnetic
      resonance imaging was performed in a 4.7T MR scanner with a shielded gradient
      system. Diffusion-weighted images (DWI) were obtained by pulsed gradient spin
      echoes (diffusion weighting factor b: 0, 500, 1000, 1500 s/mm2). Quantitative ADC
      images were calculated from DWIs by fitting signal intensities against b-factors.
      Fifteen minute cardiac arrest was induced in the magnet by electrical
      fibrillation. Resuscitation was also carried out in the magnet, using a pneumatic
      vest for remotely controlled closed chest cardiac massage. Seven of 10 animals
      were resuscitated successfully and subsequently monitored for 3 h. During cardiac
      arrest, ADC declined from 678 +/- 79 x 10(-6) to 430 +/- 128 x 10(-6) mm2/s (63%
      of baseline). In the successfully resuscitated animals ADC returned to 648 +/-
      108 x 10(-6) mm2/s within 30 min and remained at this level throughout the 3 h of
      recirculation. Regional evaluations of ADC revealed a transient overshoot in
      brainstem and basal ganglia to 114% of control at 15 min before returning to
      baseline values after 40 min. Failure of cardiac resuscitation prevented ADC
      normalization and led to its further decline to below 50% of control. Postcardiac
      arrest normalization of ADC maps correlated with homogeneous return of ATP,
      glucose, and lactate to near normal, whereas failure of ADC normalization was
      associated with depletion of ATP and glucose and severe lactate accumulation. In
      conclusion, our data indicate, that normalization of ADC is a reliable indicator
      of cerebral recovery after resuscitation from cardiac arrest.

PMID- 8544650
TI  - Radiofrequency magnetic field gradient echoes have reduced sensitivity to
      susceptibility gradients.
AB  - The amplitudes of gradient-echoes produced using static field gradients are
      sensitive to diffusion of tissue water during the echo evolution time. Gradient
      echoes have been used to produce MR images in which image intensity is
      proportional to the self-diffusion coefficient of water. However, such
      measurements are subject to error due to the presence of background magnetic
      field gradients caused by variations in local magnetic susceptibility. These
      local gradients add to the applied gradients. The use of radiofrequency (RF)
      gradients to produce gradient-echoes may avoid this problem. The RF magnetic
      field is orthogonal to the offset field produced by local magnetic susceptibility
      gradients. Thus, the effect of the local gradients on RF gradient-echo amplitude
      is small if the RF field is strong enough to minimize resonance offset effects.
      The effects of susceptibility gradients can be further reduced by storing
      magnetization longitudinally during the echo evolution period. A water phantom
      was used to evaluate the effects of background gradients on the amplitudes of RF
      gradient-echoes. A surface coil was used to produce an RF gradient of between 1.3
      and 1.6 gauss/cm. Gradient-echoes were detected with and without a 0.16 gauss/cm
      static magnetic field gradient applied along the same direction as the RF
      gradient. The background static field gradient had no significant effect on the
      decay of RF gradient-echo amplitude as a function of echo evolution time. In
      contrast, the effect of the background gradient on echoes produced using a 1.6
      gauss/cm static field gradient is calculated to be significant. This analysis
      suggests that RF gradient-echoes can produce MR images in which signal intensity
      is a function of the self-diffusion coefficient of water, but is not
      significantly affected by background gradients.

PMID- 8544651
TI  - Measurement of kinetic perfusion parameters of gadoteridol in intact myocardium:
      effects of ischemia/reperfusion and coronary vasodilation.
AB  - Quantitation of myocardial perfusion is feasible using contrast enhanced magnetic
      resonance imaging. A method to quantitate myocardial blood flow is provided by
      the Kety model modified to account for a diffusable tracer such as gadoteridol.
      In the present study, perfusion parameters of the modified Kety model (partition
      coefficient and extraction efficiency) were determined for gadoteridol in intact
      myocardium using a constant flow, isolated, perfused heart model. Perfusion
      conditions included hearts with normal perfusion, hearts made globally ischemic
      for 20 min then perfused normally, and hearts whose coronary flow was more than
      doubled with 9 microM adenosine. T1 relaxation times were rapidly measured at 0.5
      T following step increases in perfusate gadoteridol concentration and at steady
      state. Both the partition coefficient and extraction efficiency were found to be
      significantly increased in ischemic/reperfused hearts compared to normal. While
      flow rates in adenosine hearts were too high for accurate extraction efficiency
      determination using this technique, the partition coefficient was no different
      between adenosine and normally perfused hearts. The method described in this
      article allowed the kinetic parameters of the modified Kety model to be
      determined in intact heart using NMR relaxation time measurements as the basis of
      the calculation.

PMID- 8544652
TI  - On the molecular spin density and the electrostatic potential as determinants of
      the relaxivity of metalloporphyrins.
AB  - The origin of the unexpectedly large relaxivity of a manganese metalloporphyrin
      is explored through computer simulations that include a description of the
      molecular spin density and the molecular electrostatic potential. These molecular
      properties describe not only the distribution of unpaired electrons in the
      coordination complex, but also a major driving force responsible for the dynamic
      behavior of the water molecules. By comparing the computed properties for the
      manganese complex with those of its congeneric iron complex, we gain insight into
      the origin of the unusually large relaxivity of the manganese metalloporphyrin.
      In the process, we learn how to use the computed molecular properties to
      formulate rules on how to modify the chemical structure of the metalloporphyrins
      to improve their relaxivity. Specifically, we show how to spatially direct the
      molecular spin density by the splitting of d orbitals and by the delocalization
      of electronic spin across unsaturated rings. We also learn how to attract water
      protons to the areas of high spin density by designing electrostatic focusing
      fields.

PMID- 8544653
TI  - Visualisation of mass transport of small organic molecules and metal ions through
      articular cartilage by magnetic resonance imaging.
AB  - Magnetic resonance imaging of water has been used to visualise the migration of
      three paramagnetic species, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4
      hydroxy-TEMPO, 1), Cu2+ ions, and copper ethylenediamine-tetraacetate (CuEDTA, 2)
      through cartilage on the femoral condyle of the chicken knee. The migration of
      copper ions is dominated by strong binding with the cartilage. In contrast, both
      1 and 2 bind weakly, and their diffusion can be followed as a progressive wave
      through the cartilage and subsequently into the trabecular bone structure.

PMID- 8544654
TI  - Assessment of the reliability of the determination of carotid artery lumen sizes
      by quantitative image processing of magnetic resonance angiograms and images.
AB  - In order to use MR imaging to assess progression or regression of
      atherosclerosis, one must have an idea of the reproducibility of the imaging and
      image processing techniques. The ability of dark-blood MRI and semiautomated
      image processing to reproducibility measure the inner boundary of the carotid
      arteries was evaluated and compared with results obtained using bright-blood MRA.
      MRI and MRA images were obtained for two normal and two diseased volunteers six
      times each over a short period of time (6 months). The carotid bifurcation was
      used to align slices from different imaging sessions. The area for each vessel
      (right and left common, internal and external carotid artery) was determined for
      the six imaging sessions. The standard deviations of each lumen area normalized
      to the average area were computed for each vessel segment for each volunteer. For
      the common, internal, and external carotids, the averaged normalized standard
      deviations for MRI were 8, 12, and 17% and for MRA were 6, 8, and 13%. Lumen
      sizes obtained by MRI and MRA were found to be not statistically different.
      Eccentric plaques not seen on MRA were visualized by MRI. In conclusion, dark
      blood MRI with semiautomated image processing yields reliable lumen areas that
      are in agreement with those obtained by MRA.

PMID- 8544655
TI  - Near-resonance spin-lock contrast.
AB  - Spin-lock and spin-tip excitations are the two magnetization components created
      by the preparatory RF pulse of an MRI contrast enhancement sequence. Only spin
      lock is inherently adiabatic, preserving spin alignment so that tissue-specific
      relaxation can generate desired saturation contrasts. Spin-tip is the rotating
      frame oscillating excitation, and generally causes nonadiabatic loss of all
      detectable magnetization. Relative levels of spin-lock and spin-tip are important
      to understand as a function of the preparatory B1 delta amplitude, resonance
      frequency offset, delta, and the pulse waveform. These MR responses can be
      accurately analyzed theoretically and numerically by using Torrey's tipped
      coordinates to formulate Bloch's equations. At near-resonance offsets,
      (delta/gamma B1) less than 2.0, spin-lock contrast (SLC) depends strongly on T2,
      due to the nature of spin-lock T1 rho relaxation in the RF pulse interval. The
      relaxation rates 1/T1 rho and 1/T2 rho apply for active B1 delta, but remain
      linear combinations of ordinary (1/T1) and 1/T2) for motionally narrowed MR. The
      SLC increases rapidly as delta decreases below 2000 Hz; carefully chosen B1 delta
      rise times avoid spin-tip losses down to 150 Hz or less. The SL saturation
      enhances or multiplies any other indirect saturation effects that may be also
      present, such as magnetization transfer. A strong near-resonance SLC multiplier
      is advantageous for clinically practical MRI sequences that use short B1 delta
      pulses and fast SE multislice scan modes. Simulations based upon spin-lock/spin
      tip theory and measured (T1,T2) yield excellent agreement with real MRI results
      for clinically practical fast multislice scans.

PMID- 8544656
TI  - Effect of melanin on phosphorus T1S in human melanoma xenografts studied by 31P
      MRS.
AB  - 31P MRS resonance ratios of tumors depend on the T1S of the phosphorus compounds.
      The objective of the 31P MRS study reported here was to investigate whether the
      phosphorus T1S of melanomas are influenced by the presence of melanin. One
      amelanotic (COX-t) and one melanotic (ROX-t) human melanoma xenograft line were
      studied at two different tumor volumes: 200 and 1000 mm3. 31P MRS was performed
      in nonanaesthetized mice at 4.7 T. The T1S were measured by using the superfast
      inversion recovery technique. Fraction of necrotic tissue in the tumors was
      determined by histological examination. The ROX-t tumors showed shorter T1S than
      the COX-t tumors at a volume of 200 mm3, where the fraction of necrotic tissue in
      the tumors was insignificant. The difference was similar in magnitude for all
      resonances. The T1S were not significantly different for COX-t and ROX-t at a
      volume of 1000 mm3, where the tumors of both lines had developed significant
      necrosis. The phosphorus T1S of melanomas without necrosis can be shortened
      significantly by the presence of melanin. The magnitude of the T1 shortening is
      similar for all major compounds. 31P MRS resonance ratios of melanomas are not
      altered significantly by correcting for effects of partial saturation.

PMID- 8544657
TI  - Localized 2D J-resolved 1H MR spectroscopy: strong coupling effects in vitro and
      in vivo.
AB  - A two-dimensional (2D) J-resolved MR spectroscopy sequence (2D J-PRESS), fully
      localized in three dimensions, has been implemented on a whole-body MR scanner. A
      modified PRESS sequence with [90 degrees-180 degrees-t1/2-180 degrees-t1/2
      acquisition] was used for voxel localization. An incremental delay (t1/2) was
      added to the intervals before and after the last slice-selective 180 degree RF
      pulse to monitor the J-evolution in a localized 2D MR spectrum. Spectra were
      recorded with phantoms containing common cerebral metabolites--alanine, N-acetyl
      aspartate, glutamine, glutamate, taurine, myo-inositol, glucose, aspartate, GABA,
      and choline at 50 mM. In conformity with previously reported results, additional
      cross-peaks due to strong coupling were monitored in many metabolites. A brain
      phantom was developed to mimic the gray matter of human brain with the
      metabolites at physiological concentrations (0.5-12 mM). In vivo 2D J-PRESS
      spectra (n = 18) of healthy human brain were in conformity with those recorded
      from the brain phantom.

PMID- 8544658
TI  - Short echo time proton spectroscopy of the brain in HIV infection/AIDS.
AB  - Short echo time proton spectra have been acquired from the brains of 30 male
      homosexual Acquired Immunodeficiency Syndrome (AIDS) patients and 12 age-matched
      control subjects on a 1.5 T MR system. The acquisition protocol used stimulated
      acquisition voxel localisation with a voxel size of 8 ml and repeat, echo, and
      mixing times of 5000, 20, and 30 ms, respectively. A single 25.6-ms Gaussian
      water suppression pulse was used with 128 spectral acquisitions and the data were
      eddy current corrected using a water reference. Baseline-corrected spectra were
      nonlinearly least squares fitted to a model function consisting of Gaussian
      functions representing the major metabolites reported in short echo proton
      spectra. Results indicate that the N-acetyl/creatine (NA/Cr) ratio is
      significantly reduced by 20% in AIDS patients [NA/Cr = 1.91 (0.51)] compared to
      control subjects [NA/Cr = 2.37 (0.25)] at short echo times.

PMID- 8544659
TI  - P-31 changes as a measure of therapy response in resistant and sensitive
      osteosarcomas implanted into nude mice.
AB  - OBJECTIVE: To determine if changes in PCr/Pi and PME can be used to predict lack
      of tumor response to chemotherapy in a murine model of a chemotherapy-resistant
      human osteosarcoma. MATERIAL AND METHODS: Cisplatin-resistant sublines were grown
      from high-grade cisplatin-sensitive human osteosarcoma. Surface coil localized
      31P NMR spectroscopy of implanted cisplatin-resistant and sensitive osteosarcoma
      tumors in nude mice was performed. RESULTS: A cisplatin-resistant subline of a
      sensitive human osteosarcoma was developed that was five times more resistant to
      cisplatin than the parent cell line. Our NMR data shows a statistically
      significant difference in the change in the PCr/Pi ratio after treatment between
      sensitive and resistant osteosarcomas at the alpha = 0.05 level. Changes in PME
      were seen in the sensitive tumors but were not statistically significant.
      CONCLUSIONS: Changes in PCr/Pi predict lack of tumor treatment response in human
      osteosarcoma implanted into nude mice with a specificity of 70% and a sensitivity
      of 54%. Monitoring of PCr/Pi in human osteosarcoma patients may allow detection
      of response to chemotherapy before conventional imaging techniques.

PMID- 8544660
TI  - In vivo magnetic resonance study of the histochemistry of coconut (Cocos
      nucifera).
AB  - Magnetic resonance imaging (MRI) and localized proton MR spectroscopy (MRS)
      techniques have been applied for studying different maturation processes in the
      histochemistry of coconut (Cocos nucifera). Images of the tender and mature
      coconut are characterized by protons of the aqueous solution present in the
      cavity and from the surrounding pulp, whereas the image of the dry coconut is
      from the protons of the fat present in the pulp. Localized proton MR spectra of
      the water present in the cavity from the tender and the mature coconut show
      several resonances due to different chemical constituents of coconut water,
      whereas typical spectra of the pulp from dry coconut reveal a profile of the
      hydrogens present in the saturated and unsaturated fatty acid chains. In
      addition, images obtained from a rancid coconut show the extent of internal
      damage and degradation due to fungal growth; the corresponding localized MR
      spectra of the coconut water reveal that several proton resonances are absent.

PMID- 8544661
TI  - Functional MRI of brain during breath holding at 4 T.
AB  - Both theoretical considerations and animal experiments predict increased signal
      intensity in brain cortex on T2*-weighted images that develops over a breath hold
      period. This has not been observed in recent human studies performed at 1.0 and
      1.5 T. To clarify this inconsistency, we undertook a study in normal volunteers
      at 4.0 T. Unlike the earlier studies, we observed a 3-10% signal intensity
      increase in the gray matter. Possible reasons for the discrepant results are
      discussed. We conclude that regional cerebral hemodynamics are observable by fMRI
      in man and this may have clinical applications.

PMID- 8544662
TI  - Event-related functional MR imaging of visual cortex stimulation at high temporal
      resolution using a standard 1.5 T imager.
AB  - The authors report the technical feasibility of measuring event-related changes
      in blood oxygenation for studying brain function in humans at high temporal
      resolution. Measurements were performed on a conventional whole-body 1.5 T
      clinical scanner with a nonactive-shielded standard gradient system of 1 ms rise
      time for a maximum gradient strength of 10 mT/m. The radiofrequency (RF)
      transmitting and receiving MR unit consists of a commercially available circular
      polarized head coil. Magnet shimming with all first-order coils was performed to
      the volunteer's head resulting in a magnetic field homogeneity of about 0.1-0.2
      ppm. The measuring sequence used was a modified 3D, first-order flow rephased,
      FLASH sequence with reduced bandwidth = 40 Hz/pixel, TR = 80 ms, TE = 56 ms, flip
      angle = 40-50 degrees, matrix = 64 x 128, field-of-view = 200-250 mm2, slice
      thickness = 4 mm, NEX = 1,128 partitions, and a total single scan time of about
      10 min. In this sequence the 3D gradient table was removed and the 3D partition
      loop acts as a time-loop for sequential measurement of 128 or 32 consecutive
      images at the same slice position. This means that event-related functional MRI
      could be performed with an interscan delay of 80 ms for a series of 128
      sequential images or with an interscan delay of 320 ms for a simultaneous
      measurement of four slices with a series of 32 sequential images for each slice.
      We used a TTL signal given by the gradient board at the beginning of every line
      loop in the measuring sequence and a self-made "TTL-Divider-Box" for the event
      triggering. This box was used to count and scale down the TTL signals by a factor
      of 128 and to trigger after every 128th TTL signal a single white flash-light,
      which was seen by the volunteer in the dark room of the scanner with a period of
      10.24 s. As a consequence, the resulting event-related scan data coincide at each
      line of the series of 128 sequential images, which were repeated in 128 x 80 ms
      or 32 x 320 ms for the single- or four-slice experiment, respectively. Visual
      cortex response magnitude measured was about 5-7% with an approximate Gaussian
      shape and a rise time from stimulus onset to maximum of about 3-4 s, and a fall
      time to the baseline of about 5-6 s after end of stimulus. The reported data
      demonstrate the feasibility of functional MRI studies at high temporal resolution
      (up to 80 ms) using conventional MR equipment and measuring sequence.

PMID- 8544663
TI  - Hepatic angiomyolipoma: value of proton (fat/water) chemical shift fast low angle
      shot (FLASH) MR imaging technique in detecting fatty tissue content.
AB  - A case of angiomyolipoma of the liver in a 43-yr-old woman is reported. Findings
      on ultrasonography (US), computed tomography (CT), and magnetic resonance (MR)
      imaging techniques are presented and the usefulness of proton (fat/water)
      chemical shift FLASH imaging to confirm the presence of intratumoral fat is
      pointed out.

PMID- 8544664
TI  - Activation of area V5 by visual perception of motion demonstrated with echoplanar
      MR imaging.
AB  - Cortical activation in visual association areas known to be responsible for the
      perception of motion was investigated in two volunteers who viewed a projected
      animated cartoon periodically "run" and "frozen" during collection of echoplanar
      MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images
      (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the
      occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating
      console. Images were analysed by time series regression modelling estimating
      power in the MR signal at the ON-OFF frequency of motion. Highly significant
      activation in response to motion perception was identified in both subjects
      bilaterally in area V5.

PMID- 8544666
TI  - "Managing" to redefine psychiatry.

PMID- 8544665
TI  - MRI evaluation of dexamethasone acetate therapy for osteoarthritis in the hand.
AB  - A patient with clinically diagnosed Stage I primary idiopathic osteoarthritis of
      the first metacarpal trapezium joint of the left hand received intra-articular
      administration of dexamethasone acetate. Compared to pretreatment T2- weighted MR
      images, greatly decreased MR signal intensity was observed in the affected joint
      space and adjacent soft tissues 2 days after dexamethasone acetate therapy. This
      was representative of reduced edema in the metacarpal trapezium joint and
      demonstrated the ability of MRI to follow pharmacological treatment for
      arthritis.

PMID- 8544667
TI  - Where are we going and why?

PMID- 8544668
TI  - Malaria, an unclear but present danger.
AB  - Malaria is an ever present danger to those who travel in endemic areas.
      Falciparum malaria may be a life-threatening condition, even when treated
      promptly and appropriately. It is important that practitioners be aware that
      international travelers are at risk for malaria. It is also important to advise
      patients to seek expert advice on malaria prevention before they travel to
      malarious areas.

PMID- 8544669
TI  - Cigarette smoking and bladder cancer in Washington County, Maryland: ammunition
      for health educators.
AB  - To investigate the frequency of cigarette smoking in patients who have been
      diagnosed with bladder cancer, data were obtained for 1507 subjects listed in the
      1975 private census of Washington County, Maryland. Case subjects were defined as
      persons at least 18 years of age diagnosed with bladder cancer (ICD code = 188.0
      to 188.9) between 1975 and 1992 for whom smoking information was available.
      Control subjects were defined as a random sample of persons frequency matched by
      age and sex to the cases. Controls were free of bladder cancer and had smoking
      information available. The odds ratio for current smokers for the association
      between smoking and bladder cancer adjusted for age and sex was statistically
      significant (OR = 1.68, 95% confidence intervals, 1.22 to 2.32). The chi-square
      trend test of the dose-response results was significant (chi-square = 11.69, df =
      1, P < .01).

PMID- 8544670
TI  - Mycobacterium marinum disease in Anne Arundel County: 1995 update.
AB  - A retrospective survey of 41 cases of culture-positive Mycobacterium marinum
      disease in Anne Arundel County, Maryland, showed that most infection was related
      to recreational exposure to the Chesapeake Bay and its tributaries. Three
      quarters of cases consisted of skin or joint/tendon infection of the upper
      extremity, particularly the hand. An empiric drug regimen for a granulomatous
      soft tissue infection in this context should include rifampin and ethambutol or
      cotrimoxazole (trimethoprim/sulfamethoxazole). A reactive tuberculin skin test in
      Anne Arundel County is more likely to represent M. marinum infection than
      tuberculous infection.

PMID- 8544671
TI  - Case report: recurrence of chronic ulcerative colitis induced by intercurrent
      cytomegalic virus infection.
AB  - An association between cytomegalovirus (CMV) and idiopathic ulcerative colitis
      has been known for more than 30 years. The CMV-associated colitis usually occurs
      in those who are either immunosuppressed or taking long-term corticosteroid
      drugs. We describe a patient who had been diagnosed with ulcerative colitis, who
      then developed a recurrence six months after glucocorticoid therapy was started.
      Despite tapering or increasing the glucocorticoid therapy, the symptoms did not
      improve. Investigations demonstrated the presence of CMV in tissue samples,
      increase in antibody titers to the CMV virus, and resolution of the colitis upon
      use of specific anti-CMV therapy.

PMID- 8544672
TI  - Geriatrics for the clinician. Inhalation therapy and the elderly: what every
      physician should consider.

PMID- 8544673
TI  - The growth and metamorphosis of Saint Joseph German Hospital.

PMID- 8544674
TI  - Comparison of "accelerated" tissue plasminogen activator with streptokinase for
      treatment of suspected myocardial infarction.
AB  - PURPOSE: A computerized decision analysis, based on the results of published
      clinical trials, assessed the risks, benefits, and costs of different
      thrombolytic regimens for suspected myocardial infarction (MI) throughout the
      likely range of clinical circumstances. DATA SOURCE: Medline search and articles'
      bibliographies. STUDY SELECTION: All studies reporting efficacy and side effects
      of thrombolysis. DATA ANALYSIS: Life-expectancy outcomes of thrombolytic
      therapies for possible MI modeled by decision analysis. RESULTS: The analysis
      allows a clinician to estimate the benefits, risks, and relative costs of
      thrombolytic therapies throughout the likely range of individual clinical
      circumstances. When applied, for example, to the average patient in ISIS-2,
      estimated gains are 150 quality-adjusted days of life (QALDs) from treatment with
      streptokinase (SK) and 255 QALDs with "accelerated" tPA (tPA). tPA costs $1,686
      more than SK, taking into account the cost of lifelong care of the extra strokes
      incurred. Nevertheless, the chances of stroke above which thrombolysis is not
      preferred are 5.0% for SK and 8.0% for tPA, with tPA remaining the preferred
      treatment for six hours after symptom onset; thereafter, SK is marginally
      preferred, but at much lower cost. Both regimens are beneficial in older patients
      provided the chances of MI and death are "average" or greater. CONCLUSION: When
      the chances of MI and death are known, decision analysis can be a useful bedside
      tool to guide thrombolytic therapy and subsequently, if needed, to review and
      defend the treatment decisions made.

PMID- 8544675
TI  - Threshold analysis and programs for prevention of HIV infection.
AB  - BACKGROUND: Measuring the economic effectiveness of HIV-infection prevention
      activities poses special challenges in terms of behavioral change and health
      outcomes assessment. METHODS: One way to address this difficulty is to employ
      threshold analysis to determine a level of cost per HIV infection averted above
      which society would seem unwilling to pay. The authors employ a cost-utility
      analytic framework to determine a monetary threshold for HIV prevention programs,
      subject base-case results to sensitivity analyses, and apply these results to the
      Centers for Disease Control and Prevention's fiscal year 1993 budget for
      extramural HIV prevention programs. RESULTS: The monetary threshold for cost per
      HIV infection averted was calculated to be $417,000 in 1993 dollars, and ranged
      from $185,000 to $648,000 depending upon the dollar amount society would be
      willing to pay per quality-adjusted life year gained. CONCLUSIONS: Economic
      evaluations of particular HIV-infection prevention activities at least can begin
      by determining whether their levels of effectiveness are above or below this
      derived monetary threshold, and refinements beyond this dichotomous evaluation
      can proceed as further data become available.

PMID- 8544676
TI  - Continuous trees and NEVADA simulation: a quadrature approach to modeling
      continuous random variables in decision analysis.
AB  - This paper introduces an improved technique for modeling risk and decision
      problems that have continuous random variables and probabilistic dependence.
      Variables are modeled with mixtures of four-parameter random variables, called
      "continuous trees." Functions of random variables are calculated using gaussian
      quadrature in a manner called "Nevada simulation" (NumErical Integration of
      Variance And probabilistic Dependence Analyzer). This technique is compared with
      traditional decision-tree modeling in terms of analytic technique, solution-time
      complexity, and accuracy. Nevada simulation takes advantage of the probabilistic
      independence in a decision problem while allowing for probabilistic dependence to
      achieve polynomial computational-time complexity for many decision problems. It
      improves on the accuracy of traditional decision trees by employing larger
      approximations than traditional decision analysis. It improves on traditional
      decision analysis by modeling continuous variables with continuous, rather than
      discrete, distributions. A Bayesian analysis using a mixed discrete-continuous
      probability distribution for cigarette smoking rate is presented.

PMID- 8544677
TI  - Using cluster analysis for medical resource decision making.
AB  - Escalating costs of health care delivery have in the recent past often made the
      health care industry investigate, adapt, and apply those management techniques
      relating to budgeting, resource control, and forecasting that have long been used
      in the manufacturing sector. A strategy that has contributed much in this
      direction is the definition and classification of a hospital's output into
      "products" or groups of patients that impose similar resource or cost demands on
      the hospital. Existing classification schemes have frequently employed cluster
      analysis in generating these groupings. Unfortunately, the myriad articles and
      books on clustering and classification contain few formalized selection
      methodologies for choosing a technique for solving a particular problem, hence
      they often leave the novice investigator at a loss. This paper reviews the
      literature on clustering, particularly as it has been applied in the medical
      resource-utilization domain, addresses the critical choices facing an
      investigator in the medical field using cluster analysis, and offers suggestions
      (using the example of clustering low-vision patients) for how such choices can be
      made.

PMID- 8544678
TI  - The relevance of searching for effects under a clinical-trial lamppost: a key
      issue.
AB  - In economic evaluations of new medical technologies, analysts often need to use
      data from randomized controlled trials. Trials are designed to achieve high
      internal validity; however, their selected populations and often highly
      artificial environments may imply low external validity. Thus, the use of trial
      data in an economic evaluation may bias the results, since economic evaluation is
      concerned not with theoretical capability in a trial but with likely performance
      in the practice environment. This paper indicates both the probable bias of one
      aspect of artificiality in the trial environment--selected populations--and a
      method of adjusting the analysis so that results will be more likely to reflect
      actual practice. The judicious use of extra-trial information can be used to
      correct the biases of clinical trials.

PMID- 8544679
TI  - Resampling techniques in the analysis of non-binormal ROC data.
AB  - The methods most commonly used for analyzing receiver operating characteristic
      (ROC) data incorporate "binormal" assumptions about the latent frequency
      distributions of test results. Although these assumptions have proved robust to a
      wide variety of actual frequency distributions, some data sets do not "fit" the
      binormal model. In such cases, resampling techniques such as the jackknife and
      the bootstrap provide versatile, distribution-independent, and more appropriate
      methods for hypothesis testing. This article describes the application of
      resampling techniques to ROC data for which the binormal assumptions are not
      appropriate, and suggests that the bootstrap may be especially helpful in
      determining confidence intervals from small data samples. The widespread
      availability of ever-faster computers has made resampling methods increasingly
      accessible and convenient tools for data analysis.

PMID- 8544680
TI  - Rank-order stability analysis (ROSA): testing pharmacoeconomic data.
AB  - In a pharmacoeconomic analysis, the validity of findings is critical because
      product ranking may influence formulary decision making. The authors present an
      approach for examining uncertainty in a pharmacoeconomic analysis that parallels
      the confidence-interval approach to statistical analysis. This method, rank-order
      stability analysis (ROSA), is a clear and comprehensive method for validating
      results of a pharmacoeconomic analysis, as it identifies and evaluates all inputs
      and values. It is a break-even analysis that identifies the specific point of
      insensitivity for all parameters analyzed in the pharmacoeconomic model. ROSA is
      proposed as the preferred method for judging the validity of results derived from
      estimated parameters in pharmacoeconomic analyses.

PMID- 8544681
TI  - Valuing the future: temporal discounting of health and money.
AB  - Normative discounted utility theory specifies that the values of all future
      outcomes (for example, those related to health and money) should be discounted at
      a constant rate. Two experiments demonstrated that, contrary to this
      prescription, decision makers use different discount rates for health-related
      decisions and money-related decisions. Temporal discountings for health and money
      were similar in that both demonstrated two biases previously found in monetary
      decisions: discount rates were inversely related to magnitude of outcome and
      length of delay. The relatively large discount rates used by the subjects suggest
      why it is often difficult to implement preventive health measures that improve
      future health.

PMID- 8544682
TI  - Ethical and scientific features of cutoff-based designs of clinical trials: a
      simulation study.
AB  - Cutoff-based clinical trial designs are geared towards balancing ethical and
      scientific concerns when it is deemed unethical or infeasible to randomize all
      patients to study treatments. In a cutoff-based design with randomization,
      patients who are the least sick based on a quantitative baseline indicator are
      assigned the control treatment, patients who are the most sick based on the same
      indicator are assigned to test treatment, and patients who are moderately sick
      based on the indicator are randomly assigned. Simulations were conducted to
      examine statistical efficiency and potential bias for designs with varying
      amounts of cutoff-based assignment and randomization. All design variations
      yielded unbiased estimates of a main treatment effect and a linear interaction
      effect. While randomization tends to lead to greater efficiency (or lower
      standard errors of treatment effect), the correlation between the binary
      treatment variable and baseline assignment variable completely determines the
      efficiency of a design.

PMID- 8544683
TI  - Accelerated tPA versus streptokinase for suspected myocardial infarction: waiting
      for our Mountain Dew.

PMID- 8544684
TI  - MR spectroscopic imaging of collagen: tendons and knee menisci.
AB  - Water molecules associated with collagen have short transverse (T2) relaxation
      times. Projection-reconstruction techniques are able to achieve an echo time (TE)
      much shorter than conventional techniques, allowing imaging of tissues with T2 <
      5 ms. Using these techniques, a conventional 1.5-T MRI human imaging system can
      directly image collagen-associated water from knee menisci and tendons in normal
      volunteers and patients. Long-T2 suppression improves the contrast between these
      structures and the surrounding tissue with long-T2 relaxation times.
      Spectroscopic imaging provides improved lipid/water registration and information
      about chemical composition and relaxation times. Direct imaging of tendons and
      menisci may provide more information about these structures and provide a new way
      to assess both injury and repair.

PMID- 8544685
TI  - Sequential dynamic susceptibility contrast MR experiments in human brain:
      residual contrast agent effect, steady state, and hemodynamic perturbation.
AB  - The stability and reproducibility of the dynamic susceptibility contrast (DSC)
      MRI method for sequential relative cerebral blood volume (relCBV) measurements
      was evaluated to validate the method for use in quantitative studies of cerebral
      hemodynamics in humans. A spin echo echo planar imaging protocol was used in
      conjunction with multiple bolus injections of the susceptibility contrast agent
      gadoteridol (GD). The effects of variation in interbolus interval (10 min to 4
      h), the number of injections (two to four), and the effect of the cerebral
      vasodilating agent acetazolamide (ACZ) were evaluated in 44 experiments performed
      with 22 normal subjects. Two fundamental observations were made. First, with
      multiple injections of GD, the change in MR signal over time was not consistent
      from first to subsequent boluses. A second bolus administered 10 min to 2 h after
      an initial bolus resulted in signal change of greater amplitude and duration,
      resulting in artifactually elevated estimates of relCBV, consistent with a
      residual effect of GD. Second, a relative steady state could be reached with
      serial injections of GD, such that the profile of subsequent boluses closely
      paralleled those of previous ones. This facilitates the reliable measurement of
      relCBV during activation, as demonstrated by use of ACZ.

PMID- 8544686
TI  - Evaluation of muscle diseases using artificial neural network analysis of 31P MR
      spectroscopy data.
AB  - Dermatomyositis is an autoimmune disease characterized by an erythematous rash
      and severe muscle weakness. 31P Magnetic resonance spectroscopy (MRS) provides
      quantitative data for longitudinal monitoring of disease status and responses to
      immunosuppressive therapy. A disease variant, amyopathic dermatomyositis,
      presents with a typical rash but no clinical muscle weakness. However, metabolic
      abnormalities in the oxidative capacity of muscles of amyopathic patients during
      exercise were detected with 31P MRS. Because MRS provided the best quantitative
      data for evaluating dermatomyositis, the 31P metabolic parameters derived from
      the MR spectra were further processed using an artificial neural network
      (XERION). The neural network analyses provided additional clinical information
      from the weighted correlations of multiple 31P parameters, namely, inorganic
      phosphate, phosphocreatine, ATP, phosphodiesters, and selected ratios. This
      investigation analyzes the relative importance of the various metabolic
      parameters for accurate patient characterization and provides insights into the
      pathogenesis of the disease.

PMID- 8544687
TI  - The role of Na+/K+ ATPase activity during low flow ischemia in preventing
      myocardial injury: a 31P, 23Na and 87Rb NMR spectroscopic study.
AB  - An increase in intracellular Na+ during ischaemia has been associated with
      myocardial injury. In this study, we determined whether inhibition of Na+/K+
      ATPase activity contributes to this increase and whether Na+/K+ ATPase activity
      can be maintained by provision of glucose to perfused rat hearts during low flow,
      0.5 ml/min, ischemia. We used 31P NMR spectroscopy to determine changes in
      myocardial energetics and intracellular and extracellular volumes. 23Na NMR
      spectroscopy, with DyTTHA3- present as a shift reagent, was used to measure
      changes in intracellular Na+ and 87Rb NMR spectroscopy was used to estimate
      Na+/K+ ATPase activity from Rb+ influx rates, Rb+ being an NMR-sensitive congener
      of K+. In hearts provided with 11 mM glucose throughout ischemia, glycolysis
      continued and ATP was twofold higher than in hearts without glucose. In the
      glucose-hearts, Rb+ influx rate was threefold higher, intracellular Na+ was
      fivefold lower at the end of ischemia and functional recovery during reperfusion
      was twofold higher. We propose that continuation of glycolysis throughout low
      flow ischemia allowed maintenance of sufficient Na+/K+ ATPase activity to prevent
      the increase in intracellular Na+ that would otherwise have led to myocardial
      injury.

PMID- 8544688
TI  - MRS imaging using anatomically based k-space sampling and extrapolation.
AB  - A comprehensive strategy for the acquisition, reconstruction, and postprocessing
      of MR spectroscopic images is presented. The reconstruction algorithm is the most
      critical component of this strategy. It is assumes that the desired image is
      spatially bounded, meaning that the desired image contains an object that is
      surrounded by a background of zeros. The reconstruction algorithm relies on prior
      knowledge of the background zeros for k-space extrapolation. This algorithm is a
      good candidate for proton MR spectroscopic image reconstruction because these
      images are often spatially bounded and prior knowledge of the zeros is easily
      obtained from a rapidly acquired high resolution conventional MRI. Although the
      reconstruction algorithm can be used with the standard 3DFT k-space distribution,
      a distribution that relies on anatomical features that are likely to occur in the
      spectroscopic image can produce better results. Prior knowledge of these
      anatomical features is also obtained from a conventional MRI. Finally, the
      postprocessing component of this strategy is valuable for reducing subcutaneous
      lipid contamination. Overall, the comprehensive approach presented here produces
      images that are better resolved than standard approaches without increasing
      acquisition time or reducing SNR. Examples using NAA data are provided.

PMID- 8544689
TI  - Application of a superparamagnetic iron oxide (Resovist) for MR imaging of human
      cerebral blood volume.
AB  - The authors describe the feasibility of dynamic MRI using a novel
      superparamagnetic iron oxide contrast agent. Resovist was injected as a bolus at
      doses of 4, 8, and 16 mumol Fe/kg bodyweight in three consented patients
      participating in a Phase 2 clinical multicenter trial for hepatic MRI. Dynamic
      images of the brain were obtained with a conventional FLASH sequence. Results
      were analyzed by evaluation of dynamic images, cerebral blood volume maps, and
      normalized signal intensity time curves. Resovist enabled rapid injections and a
      dose-dependent strong reduction in gray and white matter signal intensity. The
      small injection volume and good tolerability may enable Resovist to serve as a
      perfusion agent. Dedicated clinical trials are warranted to assess the potentials
      of Resovist for perfusion MRI and fMRI.

PMID- 8544690
TI  - MR pulsatility measurements in peripheral arteries: preliminary results.
AB  - Phase contrast flow velocity measurements were performed in six healthy
      volunteers and 30 patients with arteriosclerotic disease. The iliac arteries were
      investigated in 8 cases and the femoral arteries in 28 cases. In the first 24
      patients, 16 evenly distributed data sets were acquired during one cardiac cycle.
      In the last 12 patients, a trigger pulse followed by the acquisition of 30 evenly
      distributed data sets was applied every second heart beat. This procedure allowed
      data to be acquired over a full heart cycle without any acquisition gap. The
      measured flow velocities were displayed as function of time. Systolic
      acceleration, postsystolic deceleration and pulsatility of flow velocity were
      calculated and compared with stenosis grades determined from DSA angiograms.
      Flattening of the flow velocity patterns was found to correlate with the local
      severity of arteriosclerotic disease.

PMID- 8544691
TI  - Estimation of average flow in ungated 3D phase contrast angiograms.
AB  - Three dimensional (3D) phase contrast angiograms contain velocity data, which is
      discarded after the reconstruction of the projections. In extension to earlier
      work on velocity quantification with ungated 2D phase data, this paper shows that
      a useful estimate of the average velocity and flow rate can be extracted from
      ungated 3D phase contrast angiograms. Simulations and experiments in a phantom
      and in vivo were performed. For pulsatile flow and strong spin saturation, an
      over-estimation of the flow rate at the net in-flow end of the imaging volume and
      underestimation at the net out-flow end was observed. Imaging at lower RF tip
      angles yielded flow rates close to the correct value within the entire imaging
      volume. In contrast to ungated 2D experiments, the flow rates determined by
      repeated 3D experiments showed no variation.

PMID- 8544692
TI  - Relaxation enhancement of the transverse magnetization of water protons in
      paramagnetic suspensions of red blood cells.
AB  - The enhancement of the water proton transverse relaxation, delta R2, brought
      about by a difference between intra and extracellular paramagnetic
      susceptibilities in a suspension of red blood cells (RBC) has been evaluated both
      experimentally and theoretically in terms of (i) the refocusing interval, delta
      180, of a CPMG pulse sequence, (ii) the difference in paramagnetic
      susceptibility, and (iii) the shape of the cell surface. At a hematocrit of 45,
      the increase in the relaxation enhancement, delta R2, with increasing delta 180,
      was a factor of two greater for the naturally biconcave RBC, than for the quasi
      spherical RBC in hypotonic suspensions. This difference could be modeled in terms
      of a transmembrane correlation time, tau = 5.5 ms, across an RBC surface
      characterized by a demagnetizing factor which differs by 0.13 from that of a
      sphere. The increase in delta R2 with increasing magnetization difference between
      the RBC and its surroundings was found to be marginally less than quadratic, both
      experimentally and from the model.

PMID- 8544693
TI  - Reversible decreases in N-acetylaspartate after acute brain injury.
AB  - N-Acetylaspartate (NAA), which constitutes the major proportion of the dominant
      resonance in proton MR spectra of brain, is localized in mature brain exclusively
      in neurons and neuronal processes. A decrease in NAA has been observed in many
      cerebral pathologies and has usually been interpreted as an index of irreversible
      neuronal loss. The authors report a follow-up study of six patients with acute
      brain damage (four from demyelinating lesion and two from mitochondrial
      encephalopathy with lactic acidosis and stroke-like episodes [MELAS]). All
      patients underwent serial MR spectroscopy examinations. The four patients with
      acute demyelinating lesions initially showed decreases in NAA in the centers of
      the lesions that ranged between 34-72% of values from homologous brain volumes in
      the other hemisphere. All four patients subsequently showed substantial recovery
      of NAA as their clinical status improved. The two patients with MELAS syndrome
      had large decreases of NAA signal (50% and 20% of normal values, respectively)
      from their occipital lobe lesions during the acute stroke-like episodes. After
      the acute phase of the illness a progressive increase of NAA in the same volumes
      was seen in both patients (to 76% and 60% of normal values, respectively). These
      results demonstrate that significant recovery of NAA can occur after acute brain
      damage. The potential contribution of reversible neuronal dysfunction (as well as
      neuronal loss) must be considered in the interpretation of decreases in the NAA
      resonance associated with acute brain pathology.

PMID- 8544694
TI  - Magnetic resonance imaging analysis of left ventricular pressure-volume
      relations: validation with the conductance method at rest and during dobutamine
      stress.
AB  - The accuracy of magnetic resonance (MR) imaging was assessed for in vivo
      measurement of the ventricular end-systolic pressure-volume relation (ESPVR) and
      preload recruitable stroke work (PRSW). The conductance catheter was used as
      reference. In 10 pigs, ventricular volumes were measured with both methods under
      different loading conditions at two levels of contractility. Increased
      contractility resulted in a significant leftward shift of the ESPVR and PRSW for
      both methods. The magnitude of these shifts was on average similar for the two
      methods; MR imaging, 6.9 ml for ESPVR, 9.3 ml for PRSW; and the conductance
      catheter, 7.4 ml for ESPVR, 9.1 ml for PRSW. It was concluded that MR imaging may
      be used for in vivo analysis of pressure-volume relations, and that its
      sensitivity for detecting contractility changes is similar to that of the
      conductance catheter method.

PMID- 8544695
TI  - In vivo measurement of partial oxygen pressure in large vessels and in the
      reticuloendothelial system using fast 19F-MRI.
AB  - Quantitative in vivo 19F-MRI was performed in a rat model to monitor partial
      oxygen pressure (pO2) using a perfluorocarbon (PFC) emulsion as contrast agent.
      On Days 1, 4, and 8 postinjection of the PFC emulsion, transaxial T1 and pO2 maps
      were acquired of the abdomen of rats that were consecutively ventilated with pure
      oxygen, air, and a mixture of 10% oxygen and 90% nitrogen. The images had a
      resolution of 0.75 mm x 0.75 mm x 2 mm and a total acquisition time of 24 min. In
      these images it was possible to distinguish between different vessels and hepatic
      and splenic tissue in the selected imaging plane. Serial 19F-MRI measurements on
      the different days postinjection of the PFC allowed to determine separately the
      pO2 of arterial and venous blood and the intracellular pO2 in macrophages of the
      liver and spleen.

PMID- 8544696
TI  - Orbital navigator echoes for motion measurements in magnetic resonance imaging.
AB  - A single "orbital" navigator echo, that has a circular k-space trajectory, is
      used to simultaneously measure in-plane rotational and multi-axis translational
      global motion. Rotation is determined from the shift in the magnitude profile of
      the echo with respect to a reference echo. Displacements are calculated from the
      phase difference between the current echo and a reference echo. Phantom studies
      show that this technique can accurately measure rotation and translations.
      Preliminary results from adaptive motion correction studies on phantom and human
      subjects indicate that the orbital navigator echo is an effective method for
      motion measurement in MRI.

PMID- 8544697
TI  - Continuous radial data acquisition for dynamic MRI.
AB  - Since image acquisition times in MRI have been reduced considerably over recent
      years, several new important application areas of MRI have appeared. In addition
      to pure static anatomic information, the evolution of a dynamic process may be
      visualized by a sequence of temporal snapshots of the process acquired within a
      short time period. This makes applications like interactive or interventional MRI
      as well as the acquisition of additional functional information feasible. For
      high temporal resolution, all these applications require a quasi real-time image
      acquisition during the time the interaction or dynamic process evolves. We
      present an approach to real-time imaging using a continuous radial acquisition
      scheme. The intrinsic advantages of radial or projection reconstruction (PR)
      techniques are used to minimize motion-related image distortions. Modifications
      of the acquisition scheme as well as dedicated reconstruction techniques are used
      to further reduce the temporal blurring due to the finite acquisition time of one
      entire data set in our approach. So far we have used this technique for the
      visualization of active joint motion.

PMID- 8544698
TI  - Shielded gradient coils on hyperbolic surfaces of revolution.
AB  - A formalism for the calculation of fields generated by current distributions on
      hyperbolic surfaces of revolution is presented and used to generate designs for
      shielded gradient coils. One application is the development of small, insertable
      coils suitable for head imaging while allowing clearance for shoulders. This
      technique demonstrates that efficient designs that offer substantial advantages
      over conventional cylindrical designs are possible.

PMID- 8544699
TI  - A methodology for co-registering abdominal MR images over multiple breath-holds.
AB  - Previous studies have demonstrated that the SNR of abdominal MR images can be
      increased by averaging images obtained in different breath-hold acquisitions. In
      this note, the authors present a simple new methodology for ensuring that images
      acquired in multiple breath-hold periods are accurately co-registered. Within
      each breath-hold, a quick coronal scout scan is followed by a longer axial scan.
      The scout is used to position the axial slices in a fixed position relative to
      the organ under examination. This MR technique can, in principle, be automated so
      as to add less than 1 s to the imaging time of the axial scan. The method can be
      used to increase SNR by signal averaging or to co-register images acquired
      during, for example, uptake of contrast agents. SNR improvement with negligible
      blurring is demonstrated in liver images acquired by this method from healthy
      volunteers.

PMID- 8544700
TI  - On the 3.35 ppm singlet resonance in proton NMR spectra of brain tissue: scyllo
      inositol or methanol contamination?

PMID- 8544701
TI  - Complications of free flap donor sites.
AB  - A variety of free tissue transfers are available for microsurgical
      reconstruction. To date little attention has been placed on the donor site, both
      from the potential for acute complications as well as long-term morbidity. In
      this review the various types of tissue transfers in different anatomical
      locations have been assessed for potential problems at the donor site. An
      assessment system is proposed to better evaluate this problem as well as to allow
      comparison of the different donor sites.

PMID- 8544702
TI  - Forearm arterial loop as an expedient source for inflow to upper extremity free
      flaps.
AB  - Challenging wounds of the upper extremity requiring free tissue transfers are
      relatively infrequent. As a direct consequence, methods to access recipient
      vessels or acceptable alternatives may not be as familiar as in the lower
      extremity. In rare circumstances, creation of an arterial loop by elevation of a
      portion of either major forearm artery provides an easily accessible, pristine
      source of inflow for a planned free flap matching vessels of comparable caliber.
      Such a maneuver may also be important to ensure preservation of optimal hand
      function by avoiding any dissection in the vicinity of essential musculotendinous
      and neurovascular structures that might reside within or adjacent to the zone of
      injury.

PMID- 8544703
TI  - Mandibular reconstruction using the double barrel fibular graft.
AB  - Five patients underwent mandibular reconstruction using the double barrel fibular
      graft from 1989 to 1994. Bony defects ranged from 7 to 14 cm. In three patients,
      two skin flaps were taken with the fibular graft for composite reconstruction. In
      order to overcome the main disadvantage of the fibular graft, i.e., small
      circumference of the bone, a harvested fibula was osteotomized into several
      portions, folded into two parallel lengths, and fixed along the inferior border
      of the mandible and the alveolar ridge. The double barrel fibular graft provided
      more than 4-cm alveolar height without damaging bone viability. In Orientals, a
      fibula is approximately 1.5 cm thick, and using a single fibular strut for
      mandibular reconstruction may result in subsequent difficulty in wearing
      conventional dentures or osseointegrated implants. All patients acquired good
      mandibular contour and enough thickness of the alveolar ridge, and could wear a
      conventional denture and eat a solid diet. This procedure seems to be superior to
      the iliac bone graft for major mandibular reconstruction because of its length,
      the possibility of three-dimensional composite reconstruction, increased bone
      thickness, and minimal donor-site morbidity.

PMID- 8544704
TI  - Vascularized omental graft to brain surface in ischemic cerebrovascular disease.
AB  - The application of vascularized omental graft for the treatment of four patients
      with ischemic cerebrovascular disease is presented. The superficial temporal
      artery and vein were used as recipient vessels, and vascular anastomosis was
      applied in an end-to-end fashion. The distal parts of the omentum were
      exteriorized as monitoring segments for about 1 week. Angiography and cerebral
      blood flow (CBF) studies were performed in all patients postoperatively. There
      were no major complications, and all patients showed increases of CBF and
      apparent clinical improvement. It is suggested that this method is effective in
      selected patients with ischemic cerebrovascular disease.

PMID- 8544705
TI  - Derivative lymphatic microsurgery: indications, techniques, and results.
AB  - Microsurgical derivative procedures to treat chronic lymphedemas of the limbs are
      reported here. Techniques used consisted of lymphatic capsule-venous anastomoses
      (in pediatric patients) and end-to-side lymphatic-venous anastomoses. Results
      after more than 5 years showed improvement in about 70% of the cases. The
      importance of an accurate preoperative diagnostic evaluation and the precise
      indications for these microsurgical procedures are discussed. Some personal
      modifications of derivative microsurgical techniques and their advantages are
      also pointed out.

PMID- 8544706
TI  - Continuous perioperative monitoring of microcirculatory blood flow in pectoralis
      musculocutaneous flaps.
AB  - Hypovolemia and hypotension in traumatized patients as well as those undergoing
      long-lasting surgical procedures lead to hypoperfusion of tissues. Combined with
      the trauma of flap elevation and the warm ischemia during performance of the
      anastomoses, hypoperfusion of flap tissues may lead to flap failure. The
      influence of hypovolemia, ischemia and reperfusion on flap macro- and
      microcirculation was studied in an acute experiment on a new musculocutaneous
      pectoralis flap developed in minipigs. Using a multichannel laser Doppler system
      we studied, simultaneously and continuously, microcirculatory flow (MBF) in both
      the skin and muscle of the flap as well as in the contralateral control skin and
      muscle in anesthetized minipigs (n = 7). Measurements were done before and after
      raising the flap, after 90 min of flap ischemia, during mild to moderate
      hypovolemia (5%, 10%, 15%, and 20% blood loss) and during and after restoration
      of blood volume. Electromagnetic flowmetry was used to measure total blood flow
      (TBF) to the flap. All animals remained hemodynamically stable during the
      experiment. The flap MBF decreased by 20% in the skin and 25% in the muscle after
      flap elevation with no changes in the control skin and muscle. After flap
      ischemia and reperfusion, MBF returned to post-elevation values while TBF showed
      a significant increase as compared to MBF (P < 0.05). Hypovolemia caused a
      gradual drop in cardiac output (25%) and mean arterial pressure (40%), but both
      recovered above the baseline after reinfusion of shed blood. Hypovolemia also
      caused a 60% reduction in MBF in both flap skin and muscle, and only 20-23% in
      control skin and muscle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544707
TI  - Sympathetic blockade of isolated rat hindlimbs by intra-arterial guanethidine:
      the effect on blood flow and arterial-venous shunting.
AB  - In order to improve the understanding of the role of sympathetic nerve
      degeneration in reimplantation failure, the hindlimbs of eight rats (Group I)
      underwent near-complete amputation. The soft tissues of the hindlimb were
      transected at the proximal thigh with the femoral artery, vein and femur left
      intact. The femoral vessels were clamped and guanethidine was infused into a
      branch of the femoral artery of the right leg of each animal, while saline was
      injected into the left leg. The clamps were removed after 15 minutes. A baseline
      preoperative injection of radiolabeled microspheres was made, and subsequent
      injections at 6, 12, 18, and 24 hours postoperation. Twelve rats (Group II) were
      then used to assess the amount of arterial-venous shunting preoperatively (n = 6)
      and at 18 hours postoperation (n = 6), by venous sampling. Blood flow to both
      limbs increased postoperation, but there was significantly more flow in the
      guanethidine treated limb at 18 and 24 hours postoperation. The amount of
      shunting was approximately 50% in both limbs at 18 hours, as compared to 10%
      preoperation. These results highlight the potential benefit of guanethidine and
      other sympathetic blocking agents in reimplantation to increase blood flow,
      decrease tissue ischemia and increase anastomotic patency rates. They also
      suggest that sympathetic nerve degeneration did not affect the volume of arterial
      venous shunting in this model, but the difference in blood flow was likely due to
      arteriolar vasospasm. Further study is needed to elucidate the clinical
      significance of sympathetic nerve degeneration in reimplantation failure.

PMID- 8544708
TI  - Influence of luminal pore size on the patency rate and endothelialization of
      polymeric microvenous prostheses.
AB  - In microvenous prosthetic surgery a continuous search for better patency rates is
      necessary to enable a clinical application. In this search for better patencies,
      modifications in the wall structure are being made. Directions found in the
      literature suggest that pore size plays an important role in achieving better
      patencies. Thus far, no study has been conducted to evaluate the influence of
      pore size on the patency rate of polyurethane microvenous prostheses. Since
      polyurethane is known to yield good patency rates, we conducted this study in
      which we compared different luminal pore sizes with regard to patency. Pore size
      varied from 0.6 to 20 microns in microvenous polyurethane-based prostheses
      (length 5-6 mm, internal diameter 1 mm). The results showed a favorable patency
      rate in the pore sizes larger than 5.0 microns (patency 75%) when compared to
      pore sizes smaller than 2.0 microns (patency 50%). This study demonstrates that
      microvenous polyurethane-based prostheses with a luminal pore size larger than
      5.0 microns may yield better patency rates than prostheses with a luminal pore
      size smaller than 5.0 microns. Further studies are currently being performed to
      elucidate the very reasons for this effect.

PMID- 8544709
TI  - Heterotopic microvascular epiphyseal plate transplantation: a new model using the
      rabbit metatarsal.
AB  - The purpose of this study is to develop a new vascularized epiphyseal plate model
      in the New Zealand White rabbit using a metatarsal epiphyseal plate having
      limited longitudinal growth potential. Such a model could be utilized in various
      experiments aimed at manipulating epiphyseal plate growth. The viability of the
      harvested live subject grafts was demonstrated with continued epiphyseal uptake
      during Tc99-MDP radionuclide bone scanning. The currently described models used
      in epiphyseal transplant research all involve long bone epiphyseal plates with
      significantly greater growth potential than the new metatarsal model. This new
      model therefore fills a void in the field by allowing investigators to transplant
      a growth plate with limited growth potential into any heterotopic site and study
      the effects of various hormonal and physical influences upon epiphyseal plate
      growth performance.

PMID- 8544710
TI  - Technique of total hepatectomy in the rat.
AB  - We report a novel one-stage technique of total hepatectomy in the rat, in which
      the liver is replaced by an autologous prosthesis. This prosthesis is obtained
      from a donor rat, and consists of the subhepatic vena cava and the left renal
      vein harvested en block. This graft is sutured with the subdiaphragmatic cava and
      linked with cuffs to the subhepatic vena cava and the portal vein in the donor
      rat. This procedure is associated with a very low operative mortality. Rats with
      glucose and plasma-expander infusions survived for a mean time of 23 +/- 9 hr.
      This technique of total hepatectomy can be considered a valid and reproducible
      model of true anhepaty for metabolic and survival studies with liver support
      systems.

PMID- 8544711
TI  - Nerve regenerating effect of short-course administration of cyclosporine after
      fresh peripheral nerve allotransplantation in the rat: comparison of nerve
      regeneration using different forms of donor nerve allografts.
AB  - There is almost universal agreement that if cyclosporine (CsA), which is a potent
      immunosuppressant, is temporarily administered after surgery, regenerated axons
      will be maintained even after withdrawal of CsA following peripheral nerve
      allotransplantation. Thus, this experimental study was conducted to investigate
      whether a difference in donor nerve form, including thickness and length,
      influences nerve regeneration after withdrawal of immunosuppression with CsA. The
      findings suggest that as a result of immunosuppression with CsA, large-diameter
      nerve grafts are better able to induce nerve regeneration than small-diameter
      grafts, and after withdrawal of the immunosuppressant, thick nerve grafts are
      also better able to preserve regenerated axons against the rejection reaction
      than thin grafts. With regard to the length of the grafted nerve, short nerve
      allografts yield higher axon counts than long ones, the same as with autografts.
      The best way to induce nerve regeneration appears to be to transplant a short,
      thick nerve allograft, which is definitely capable of inducing many regenerated
      axons.

PMID- 8544713
TI  - Modified surgical approach of the rat sciatic nerve.

PMID- 8544712
TI  - Study on microvascular anastomosis of arteries with absorbable polyglyconate
      suture.
AB  - A synthetic, monofilament, slowly absorbing suture material, polyglyconate suture
      was tested to determine its suitability for use in microarterial anastomoses
      under ordinary tension and under undue tension. Microvascular repair of 34 rat
      femoral arteries averaging 0.63 mm in diameter using 8-0 polyglyconate suture on
      an atraumatic needle gave an immediate patency rate of 100% and a late patency
      rate of 94.1% after 1 to 24 weeks. Microanastomoses of 30 rabbit femoral arteries
      averaging 1.43 mm in diameter using 8-0 polyglyconate suture on an atraumatic
      needle gave an immediate patency rate of 100% and a late patency rate of 96.7%
      when a vessel segment of 3 to 7 mm was resected. Morphological studies included
      light microscopy and scanning electron microscopy. The results showed that
      polyglyconate suture retains tensile strength for an adequate period to allow
      vascular healing and causes a less pronounced tissue response than nonabsorbable
      nylon suture. Complete absorption of the suture material was followed by a
      complete regeneration of the vessel wall. These results demonstrated that
      absorbable polyglyconate suture might be suitable for microvascular anastomosis
      of arteries under ordinary tension and under tension to a certain degree.

PMID- 8544714
TI  - [Afebrile infections in adult patients with acute leukemia].
AB  - Characteristics of afebrile infection episodes among adult patients with acute
      leukemia are here described. Afebrile episodes represented 14.3% of all
      infections. They significantly differed from the febrile episodes because: 1)
      they prevailed among patients with granulocyte count greater than 500/mm3 (p <
      0.001); 2) they often involved patients in complete remission (p < 0.0002); 3)
      they affected more frequently the kidney and urinary tract than febrile
      infections (p = 0.0005) and 4) they lacked lung involvement (p < 0.01). The rate
      of documented infections by cultures, cytology or serological tests was not
      different between both infection types. Observed mortality during afebrile
      episodes was threefold less than febrile infections; this difference, however,
      did not reach statistical significance. In conclusion, afebrile infection in
      acute leukemia is a distinct clinical entity, unlike febrile infection.

PMID- 8544715
TI  - [Renal acidification mechanism disorders in patients with osteoporosis].
AB  - Eight patients (6 women and 2 men) with osteoporosis caused or aggravated by
      renal acidification defects are presented. Three of the female patients were
      premenopausal; the others were 9, 20 and 22 years postmenopausal, and two of them
      were on hormonal replacement therapy. Two patients had nephrolithiasis: one male
      with recurrent calcium phosphate stones and a left sided staghorn calculus, and
      one female with nephrocalcinosis due to medullary sponge kidney and
      hypercalciuria (patients No. 1 and 2, respectively, Table 1). In the remaining
      subjects, clinical suspicion was based on: a) Hip fracture in a 44-yr-old
      premenopausal female without any risk factor (No. 3, Table 2). b) Several
      vertebral compression fractures in a 45-yr-old male without hypogonadism or other
      predisposing factors (No. 7, Table 2). c) Lack of response to antiosteoporotic
      therapy in 3 women (patients No. 4, 6 and 8, Table 2). Serum bicarbonate levels
      and urine acidification capacity were studied in all patients. Three had low
      serum bicarbonate (two of whom showed high fractional excretion of bicarbonate),
      four had a distal defect, and one had a mixed form. Serum creatinine and
      potassium, and venous blood pH were normal in all cases, suggesting incomplete
      renal tubular acidosis. Bone mineral density in Z-score (means +/- s.e.m.) was -
      1.75 +/- 0.08 in the lumbar spine (n = 8), and - 1.57 +/- 0.09 in the femoral
      neck (n = 4) [Tables 1 and 2; Figs 1 and 2]. Following one year treatment with
      oral sodium bicarbonate and potassium citrate, total skeletal calcium increased
      by 3-10% in five of the patients. Whereas the high prevalence of renal
      acidification defects among renal stone formers with or without hypercalciuria is
      well acknowledged, renal tubular acidosis is not included in the list of entities
      causing secondary osteoporosis. As shown in 6 patients of this series, incomplete
      RTA should be considered as another disease capable of causing osteoporosis or
      worsening involutional bone loss.

PMID- 8544716
TI  - [Renal hemodynamics and blood pressure. Intrarenal Doppler evaluation].
AB  - This new technique has been used to evaluate renal hemodynamic pattern because
      although it is impossible to measure the arterial diameter, the doppler signal is
      easier to obtain than in the renal artery. In order to define normal patterns we
      studied 67 untreated patients, with no evidence of acute or chronic disease,
      using intrarenal doppler ultrasound technique. The mean (SD) systolic, diastolic
      and mean renal doppler deviation were 2.144 +/- 0.54, 0.688 +/- 0.23 and 0.604 +/
      0.28 kHz respectively. The mean peak doppler frequency was 1.136 +/- 0.34 kHz,
      and Stuart, Pourcelot and Gosling indexes were 3.6 +/- 0.8, 0.67 +/- 0.06 and
      1.31 +/- 0.39 respectively. The mean ejection time was 0.28 +/- 0.03 s. A
      multiple regression analysis was performed and a marked negative correlation was
      found between all the velocities and age. Arterial blood pressure was the second
      determinant of velocity. To examine the influence of blood pressure in renal
      hemodynamics, we compared normal (diastolic blood pressure below 90 mm Hg) and
      hypertensive patients (13 patients in each group) matching them for age, sex,
      weight and height. RESULTS: In addition to blood pressure differences (caused by
      design) we found that systolic arterial doppler deviation was higher in
      normotensive than in hypertensive patients (2.152 +/- 0.48 vs 1.730 +/- 0.44 kHz.
      p < 0.05). As arterial area probably decreases with age, it is possible that low
      velocity of flow might be caused by an effective plasmatic renal flow fall.
      Contrary to expected, hypertensive patients blood flow velocity was lower than in
      normal which suggests that intrarenal arteriolar resistance was
      increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544717
TI  - Motor activation time in Parkinson's disease.
AB  - Motor activation time (MAT), considered in the present work as the actual
      intracerebral processing delay during a reaction time (RT) task, was assessed in
      17 patients with Parkinson's disease (PD) and in 7 age-matched healthy
      volunteers. MAT was calculated by subtracting from the premotor RT the afferent
      and efferent times obtained by sensory and motor evoked potentials. When compared
      with healthy volunteers, patients exhibited significantly (p < 0.02) prolonged
      MATs. In a smaller group of 9 PD patients MAT and the auditory P3 event related
      potential were assessed while on antiparkinsonian treatment and after a 12-hour
      withdrawal period. During the off medication condition patients showed a
      significant slowing (p < 0.01) of MAT values without any remarkable change in P3
      latency or amplitude. These results suggest that MAT slowing indicates an
      abnormal function of the dopaminergic mechanism involved in the initiation of
      movement which is not related to changes in the arousal or cognitive state.

PMID- 8544718
TI  - Detection of human papillomavirus in juvenile laryngeal papillomatosis using
      polymerase chain reaction.
AB  - We examined the presence and subtypes of human papillomavirus (HPV) in 20
      paraffin-embedded samples (from 12 patients) of juvenile laryngeal papillomatosis
      using the polymerase chain reaction (PCR). The biopsies had been stored for
      months to 12 years. Due to the great genetic variability of HPV, we selected a
      conservative sequence of the viral genome (L1 region) to identify the vast
      majority of the subtypes. Positive results were obtained by one-step PCR
      amplification with the MY09-11 consensus primers (L1 region) in only 10 of the
      cases. After a two-step amplification (nested-PCR) with GP5-6 primers the 20
      samples proved to be positive demonstrating the higher sensitivity of this
      method. In order to amplify a highly variable region of the genome (E6), specific
      primers for HPV types 6 and 11 (H6/11 L1-R2) were used. 7/12 patients were
      positive for this subtype. Since more that one subtype has been reported in the
      same sample, the presence of HPV 6-11 sequences does not exclude that other
      subtypes might be involved. The results of this study show that: 1) HPV is
      present in JLP. 2) The most frequent HPV subtype involved was from the 6-11
      group. 3) PCR can be successfully used in archived tissue routinely processed in
      a laboratory of pathology.

PMID- 8544719
TI  - [Effects of experimental ascites on diaphragm strength].
AB  - We studied the strength developed by the diaphragm during progressive ascitis
      induction (40 up to 280 ml/kg wt) and the changes in the radium of curvature in
      relation with its strength in 6 anesthetized dogs. Force generation of the
      diaphragm was assessed with the Pdi obtained with bilateral phrenic nerve
      stimulation at 60 Hz. In relation to increases in the abdominal liquid, the
      thoraco-pulmonary compliance decreases (p < 0.05) from 10.1 to 6.8 ml/kg/cm H2O.
      The radius of curvature increases 158% from the basal values; the calculated
      basal tension was 347 +/- 43, final 448 +/- 32 cm H2O/cm. The diaphragmatic
      length in percent of the basal value was 138%. The X-rays findings showed
      cephalic displacement, diaphragmatic flattening and stretching. The Pdi obtained
      should be the result of a complex interaction between the diaphragmatic geometry,
      the length, the degree of stretching during the contraction and preload. We can
      describe the changes in Pdi in 2 steps: initial increase and final decrease,
      associated to high Pga at the beginning and a low one later. First the Pdi
      increases by the Pga without significant changes in the Pes. The fact is that an
      increase in Pga can be related with cephalic displacement of the diaphragm with
      stretching and shortening of the radius of curvature and decreases in the
      abdominal compliance. The final decreases in the Pdi could be related with
      overstretching and decreases of the radius of curvature.

PMID- 8544720
TI  - [Prevalence of arterial hypertension in a rural population of Buenos Aires].
AB  - We screened 1.080 individuals of both sexes between 15 and 75 years old of a
      rural population of Gral. Belgrano (Prov. of Bs As) in order to assess: 1)
      prevalence of hypertension (HP) 2) state of awareness of the population about
      hypertension and 3) treatment and control of the hypertensive population. The
      sample represented 11% of the population between 15 and 75 years old. BP was
      measured 3 times in one occasion and the average of these determinations was used
      to state prevalence. The prevalence of HP (BP > or = 140 and/or 90 mmHg) was
      39.8% (35.1% for women and 44.9% for men, P < 0.001) (Fig. 2). The prevalence of
      diastolic hypertension (DHP) was 22.4% in women and 30.1% in men whereas the
      prevalence of systolic hypertension (SHP) was 9.6% and 12% respectively. 47% of
      the hypertensive individuals were aware of being hypertensive and 13% of this
      group were without pharmacological treatment. If we consider the group who was
      treated (34%) only 7.6% were controlled with the medication. A very high
      prevalence of this disease was detected in this population. It will be necessary
      to evaluate obesity and high salt and alcohol intake. The reduction of these risk
      factors will be of great value for the primary prevention of this disease.

PMID- 8544721
TI  - [Echocardiography in the evaluation of cardiac involvement in seronegative
      spondylo-arthropathies].
AB  - To evaluate the involvement of the heart in patients with seronegative
      spondyloarthropathies by echodopplercardiography, 35 patients including 20 with
      ankylosing spondylitis, 10 with Reiter's syndrome and 5 with psoriatic arthritis
      (21 men and 14 women, with ages ranging from 17-68 years and averaging 38.5) were
      studied. Most were asymptomatic with respect to the cardiovascular system
      (65.71%) and 12 oligosymptomatic with palpitations as their main complaint. Each
      patient had an echocardiogram and electrocardiogram. A two-dimensional
      echocardiogram demonstrated alterations in 19 patients (54.29%), 28.58%
      asymptomatic and 25.71% symptomatic. This study revealed most of lesions (17/19
      84.47%) followed by the Dopplerechocardiography (10/19-52.63%) and the one
      dimensional echocardiography (9/19-47.36%). Abnormal aortic valves were found in
      10 patients, in 7 thickenning and in 3 calcifications. The mitral valve was
      involved in 11 patients, in 8 thickenning, in 1 calcification and in 2 valve
      prolapse. In ankylosing spondylitis aortic valve disease was found in 8 patients.
      Dopplerechocardiography evidenced the presence of aortic regurgitation in 4
      patients and mitral insufficiency in 3. The Q-T interval was increased in 19
      patients, there was one first degree auriculoventricular block, one right branch
      block and one sinus bradicardia. Thus the echocardiogram is an excellent
      noninvasive method to disclose cardiac disturbances in patients with seronegative
      spondyloarthropaties.

PMID- 8544722
TI  - [Lactose digestion by milk fermented with Lactobacillus acidophilus and
      Lactobacillus casei of human origin].
AB  - The aim of the present study was to determine whether a fermented milk containing
      Lactobacillus casei and Lactobacillus acidophilus strains isolated from human
      subjects (CFM) and developed by CERELA (Centro de referencia para Lactobacilos)
      is better tolerated than regular milk (RM) by subjects with lactase deficiency (<
      1 unidad) and lactose intolerance. We studied the digestion of the lactose
      present in the two milk preparations which were administered to 18 healthy
      subjects with lactase deficiency and 12 control subjects. Each subject ingested
      in random sequence on different days, 480 ml CFM, 480 ml RM and 240 ml CFM and
      240 ml RM. Breath hydrogen (H2) test was used to measure lactose absorption and
      orocecal transit time (OCTT). The peak H2 ppm results after 480 ml of CFM were
      ingested, reached 19.5 +/- 12.1 ppm. The same reading when 480 ml of RM were
      ingested was 52.6 +/- 31.9 ppm (p < 0.008). The results also showed that 480 ml
      of CFM delayed OCTT median 111.0 +/- 6.78 min versus 54.0 +/- 5.09 min of RM (p <
      0.001) and reduced the development of symptoms (p < 0.08) such as bloating (p <
      0.05), borborygmi (p < 0.025) diarrhea (p < 0.05) and abdominal colics (p <
      0.05). In spite of the small number of cases studied, it seems justified to
      conclude that CERELA fermented milk significantly influences lactose digestion
      and minor development of symptoms in lactase-deficient subjects and lengthens
      significantly the orocecal transit time compared with regular milk.

PMID- 8544723
TI  - [Medical treatment of 44 patients with anal canal carcinoma. Argentinian
      Intergroup for the treatment of gastrointestinal tumors (IATTGI)].
AB  - In order to investigate the medical treatment of anal canal carcinoma (ACC), 27
      patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an
      alternating schedule. Eleven pts received mitomycin C, fluorouracil and
      radiotherapy, in a concurrent scheme. Finally, six pts were included in a new
      outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and
      concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18
      achieved complete response. All of them are disease free until now. With the
      second scheme, 7/10 pts had a complete response and 5 of them are alive and
      disease free. All the pts included in the last schedule (6/6) achieved complete
      remission. There were no deaths related to toxicity. Our experience is one of the
      earliest in oncology using cisplatin as a first line drug, in the non-surgical
      treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is
      manageable, and its effectivity is similar to other schedules, as observed in our
      last scheme.

PMID- 8544724
TI  - [Pregnancy with testicular spermatozoa].
AB  - In a patient with a diagnosis of congenital vas deferens agenesis we decided to
      carry out a microsurgical epididymal sperm aspiration in order to attempt an in
      vitro fertilization (IVF). Since during scrotal exploration no epididymus was
      found (probably as a consequence of a previous surgical biopsy) a testicle biopsy
      was performed. The latter yielded a few hundred sperms which were injected within
      the cytoplasm of his wife's oocytes (ICSI technique). Of the 18 oocytes, 3 were
      harmed during the procedure and 16 hours later signs of normal fertilization were
      detected in 6 of them, followed by the development of 4 embryos. These were
      transcervically transferred to the uterus, 3 in 8 cell stage and 1 in 6 cell
      stage; previously a 20 micron hole had been made with acid Tyrode solution in the
      pelucida zone of each embryo. Fifteen days later, the result of the HCG beta
      subunit assay was positive and a month later a single 19 mm normal embryo was
      detected by ultrasound echography.

PMID- 8544725
TI  - [Cardiac and renal insufficiency with consciousness changes].

PMID- 8544726
TI  - [Synthetic oligonucleotides and their application in gene therapy].
AB  - Synthetic oligonucleotides are useful for research in molecular biology, for
      clinical diagnosis and for the development of new therapeutic agents. In fact,
      their application to gene therapy has given rise to a new field termed antisense,
      enabling the synthesis of a new generation of drugs. The procedure is based on
      coupling an oligonucleotide with mRNA to yield the protein whose production by
      the host is to be prevented, and thus through diverse pathways inhibiting gene
      expression. In medicine, a start has been made by applying antisense techniques
      in human drug trials, particularly as antiviral and antileukemic agents.

PMID- 8544727
TI  - [Mucicarmine, p53, and mesothelioma].

PMID- 8544728
TI  - [Corticosteroids in chronic obstructive pulmonary disease].

PMID- 8544730
TI  - [Errors and culprits].

PMID- 8544729
TI  - [Frozen red blood cells].

PMID- 8544731
TI  - [Polymerase chain reaction: detection and characterization of Trypanosoma cruzi
      strains in chagasic children].

PMID- 8544732
TI  - [Molecular diagnosis of Gaucher disease in Argentinian patients].

PMID- 8544733
TI  - [Do hypercalciuria and hyperuricosuria produce the same tubular damage?].

PMID- 8544734
TI  - [What did Oscar Wilde die from?].

PMID- 8544735
TI  - Ecology of Triatoma rubrovaria (Hemiptera, Triatominae) in wild and peridomestic
      environments of Uruguay.
AB  - This paper describes population structure, spatial distribution and habitat
      selection of wild and peridomestic populations of Triatoma rubrovaria (Blanchard,
      1843). Field studies were carried out at Las Piedras and La Bolsa in the Northern
      Department of Artigas, Uruguay. A semicircular sampling area, divided in seven or
      eight triangular sectors was sequentially examined from October 1990 to November
      1991. At Las Piedras (typical wild habitat) 1063 T. rubrovaria bugs were
      collected from 84% of the rocky outcroops ("pedregales"). Abundance varied by
      season peaking in October-November (spring). Throughout the year, most of the
      population was made up of third, fourth and fifth instar nymphs; adults were
      found from October to March. In the peridomestic environment of La Bolsa, however
      T. rubrovaria was less common and showed a more irregular instar distribution.
      Colonized ecotopes, were those close to houses. In both sites T. rubrovaria was
      mainly associated with the geckonid Homonota uruguayensis and the cockroach
      Blaptica dubia.

PMID- 8544736
TI  - Fate of Bacillus sphaericus after ingestion by the predator Belostoma micantulum
      (Hemiptera: Belostomatidae).

PMID- 8544737
TI  - Simian malaria at two sites in the Brazilian Amazon. I--The infection rates of
      Plasmodium brasilianum in non-human primates.
AB  - The parasite that causes simian malaria in the Brazilian Amazon, Plasmodium
      brasilianum, is infective to man. In this region, where humans live within and in
      close proximity to the forest, it was suspected that this parasite could be the
      cause of a zoonosis. A study was performed in the areas surrounding two
      hydroelectric plants in the Amazon, Balbina and Samuel, aiming at determining the
      zoonotic potential of this parasite. P. brasilianum was detected in,
      respectively, 15.8% and 9.9% of 126 and 252 primates belonging to seven and eight
      species examined from Balbina and Samuel. The highest malaria infection rates
      were found among the red-howler monkey Alouatta seniculus straminea (32.3%), the
      bearded-saki Chiropotes satanas chiropotes (50%) and the spider-monkey Ateles
      paniscus paniscus (2[1+]) from Balbina and in the squirrel-monkey Saimiri ustus
      (21%) and the black-faced-spider-monkey Ateles paniscus chamek (28.6%) from
      Samuel.

PMID- 8544738
TI  - An outbreak of dengue in the State of Ceara, Brazil.

PMID- 8544739
TI  - Genetic variability and differentiation between populations of Rhodnius prolixus
      and R. pallescens, vectors of Chagas' disease in Colombia.
AB  - Enzyme polymorphism in Rhodnius prolixus and R. pallescens (Hemiptera,
      Reduviidae), principal vectors of Chagas' disease in Colombia, was analyzed using
      starch gel electrophoresis. Three geographic locations were sampled in order to
      determine gene flow between populations and to characterize intra- and
      interspecific differences. Of 25 enzymes assayed 10 were successfully resolved
      and then used to score the genetic variation. The enzymes PEPD, GPI, PGM and ICD
      were useful to differentiate these species and PGD, PGM and MDH distinguished
      between sylvatic and domiciliary populations of R. prolixus. Both polymorphism
      and heterozygosity indicated greater genetic variability in sylvatic habitats (H
      = 0.021) compared to domiciliary habitats (H = 0.006) in both species. Gene flow
      between sylvatic and domiciliary populations in R. prolixus was found to be
      minimal. This fact and the genetic distance between them suggest a process of
      genetic isolation in the domiciliary population.

PMID- 8544740
TI  - Use of isozyme patterns in the identification of Biomphalaria tenagophila
      (D'Orbigny, 1835) and B. occidentalis (Paraense, 1981) (Gastropoda: Planorbidae).
AB  - Two sibling species of Biomphalaria, B. tenagophila and B. occidentalis were
      identified using isozyme patterns obtained by horizontal gel electrophoresis. Six
      diagnostic enzymatic loci were identified in digestive gland homogenates. The
      results enable us to distinguish the species, calculate the Nei's coefficient of
      genetic similarity, and provide a basis for making inferences about the pattern
      of these two planorbid species colonization and distribution.

PMID- 8544741
TI  - The development of species of Leishmania Ross, 1903 in Lutzomyia longipalpis
      (Lutz & Neiva, 1912).
AB  - The development of four isolates of Leishmania from foci of American cutaneous
      leishmaniasis was studied in Lutzomyia longipalpis. The suggestion that the
      differences in the development of the Leishmania in the invertebrate host are of
      great taxonomic significance was confirmed. The pattern of development of three
      strains was typical of parasites of the subgenus Leishmania, the other was
      similar to Leishmania of the subgenus Viannia. The identification of the strains
      using other criteria is in agreement with biological characterization. The
      results show that the morphological and morphometric study of promastigotes do
      not clearly define the taxonomic position of the parasites but other studies are
      needed to confirm this.

PMID- 8544742
TI  - Repair of schistosomal intestinal vascular lesions after curative treatment.
AB  - The process of repairing intestinal vascular lesions induced by schistosomiasis
      in mice was studied before and after curative chemotherapy, by means of
      histopathology coupled with injections of the mesenteric veins with India ink or
      plastic, in this case followed by corrosion in strong acid. The granulomas were
      avascular, mainly formed while within blood vessels, and were associated with
      distortion of the intestinal vasculature in their proximity, represented by
      tortuosities, focal dilatation, narrowing, and anastomosis of the mucosal and
      submucosal veins. Two to four months after cure of schistosomiasis involuting
      granulomas were seen to be slowly vascularized, a process going from the
      periphery toward the center of the granulomas. No intravascular granulomas were
      seen four months after treatment. The previously distorted mucosal and submucosal
      veins gradually regained their normal appearance, only a slight tortuosity
      remaining.

PMID- 8544743
TI  - Effects of three organophosphorus insecticides in the reproductive potential of
      Culex quinquefasciatus.
AB  - A Culex quinquefasciatus Say 1823 strain with resistant genes to organophosphates
      was tested in the laboratory to know the reproductive potential after exposure,
      as larvae, at the LC30 and LC70 (mg/l) of three organophosphorus insecticides:
      malathion, chlorpyrifos and methyl-pirimiphos. Data showed that fecundity was
      decreased significantly by malathion at LC30 = 0.0025 and LC70 = 0.0075, whereas
      fertility has a no significant decrement by chlorpyrifos and methyl-pirimiphos at
      the LC70 (0.000016, 0.00043). The sexual index was affected by chlorpyrifos and
      methyl-pirimiphos showing a greater number of adult females.

PMID- 8544744
TI  - Residual effect of lambdacyhalothrin on Triatoma infestans.
AB  - Insecticidal residual effect and triatomine infestation rates in houses of a
      community fumigated with lambdcyhalothrin (Icon) are reported. No mortality was
      observed in 5th-instar Triatoma infestans nymphs in 72-hr exposure test on three
      different surfaces, one month after fumigation for a dose of 31.5 mg am/m2.
      However, during post-exposure observation a mortality of 60% was recorded for
      those insect exposed on sprayed woodboard. The results observed with mud
      containing treated walls, were markedly poorer (0% of mortality). Twelve month
      after spraying 40% of mortality was observed on first-instar T. infestans nymphs
      in 72-hr exposure test on woodboard, but lower mortality rates were observed in
      mud-containing materials. When the effect of deltamethrin (109 mg ai/m2) and
      lambdcyhalothrin (94 mg ai/m2) was compared, the former did not appear to be
      superior at similar loads. Both have showed a mortality rate of 30% on 5th-instar
      T. infestans nymphs three months post-fumigation. The dose utilized in the field
      fumigation was enough to get a significant (p < 0.0001) control of triatomine
      domestic infestation, since it was sufficient to keep 95% of the houses
      uninfested throughout 21 months following treatment, when compared with baseline
      situation. A remarkable knock-down effect on adult and nymphs forms of the insect
      and a high in situ mortality were observed as a result of its application, even
      at very low doses.

PMID- 8544745
TI  - An attempt to control Phlebotomine sand flies (Diptera: Psychodidae) by residual
      spraying with deltamethrin in a Colombian village.
AB  - An attempt was made to control phlebotomine sand flies biting indoors in a rural
      community near Cali, Colombia, using the residual insecticide "K-Othrine"
      (deltamethrin) sprayed on the inside walls of houses. Twelve houses were divided
      into matched pairs based on physical characteristics, one house in each pair
      being left untreated while the inside walls of the other were sprayed with 1%
      deltamethrin at a concentration of 500 mg a.i./m2. Sand flies were sampled each
      week using protected human bait and sticky trap collections for four months after
      spraying. The number of sand flies (Lutzomyia youngi) collected on sticky traps
      was significantly lower (P = 0.004) in the untreated houses than in the treated
      ones with which they were matched. This difference was not significant for L.
      columbiana; the other anthropophilic species were not present in large numbers.
      The numbers collected on human bait in treated and untreated houses were not
      significantly different for either species. Activity of the insecticide as
      determined by contact bioassays remained high throughout the study and failure to
      control the insects was attributed to two factors: the tendency of sand flies to
      bite before making contact with the insecticide and the fact that the number of
      sand flies that entered houses represented a relatively small proportion of the
      population in the wooded areas surrounding the settlement in the study.

PMID- 8544746
TI  - Activity of 9-acridanone-hydrazone drugs detected at the pre-postural phase, in
      the experimental schistosomiasis mansoni.
AB  - The compound Ro-15.5458/000, derivative in the class of 9-acridanone-hydrazones,
      was found to be effective against Schistosoma mansoni in mice, killing almost all
      the skin schistosomules (24 hr after infection), when administered at the dose of
      100 mg/kg. In experiments carried out with Cebus monkeys, the drug was shown to
      be fully effective at 25 mg/kg, 7 days after infection. These data, associated
      with the good results obtained earlier at the post-postural phase of
      schistosomiasis, allow the inference that this promising compound may be
      important in the set of antischistosomal drugs, depending on further
      toxicological and clinical tests.

PMID- 8544748
TI  - The year of Louis Pasteur International Symposium: "From spontaneous generation
      to molecular evolution".

PMID- 8544747
TI  - The interaction between poultry and Triatoma infestans Klug, 1834 (Hemiptera:
      Reduviidae) in an experimental model.
AB  - This paper compares the predation pressure that ducks and chickens exert on
      triatomines. For the tests, these birds were placed in individual boxes together
      with a known number of Triatoma infestans and left to interact from 6 p.m. till
      the next morning, involving a long lasting period of complete darkness limited by
      two short-term periods of semi-darkness. There was a shelter which could prevent
      the bugs from being predated. The number of live and dead triatomines was
      recorded, considering missing bugs as predated by the birds. Ducks exhibited a
      greater predatory activity than chickens, that could be due to a long term active
      period at night while chickens sleep motionless from sunset to dawn. Surviving
      triatomines that had fed on chickens outnumbered those fed on ducks suggesting
      that these were less accessible to the triatomine biting. If ducks are better
      than chickens to detect and eat bugs and to interfere with their feeding in the
      field, an increase in duck number might help to diminish triatomine density.
      Further research is needed to determine the feasibility of application of these
      experimental results.

PMID- 8544749
TI  - An assay for loss of heterozygosity in vivo at the Dlb-1 locus.
AB  - Loss of heterozygosity (LOH) is a frequent event in many tumours, resulting in
      the loss of tumour suppressor genes and ultimately magnifying the number of cells
      with a mutant phenotype. We have used the Dlb-1 locus as a simple quantitative
      assay for LOH in vivo. Mutations of the dominant Dlb-1b allele are readily
      detected in heterozygous (Dlb-1a/Dlb-1b) mice by the loss of histochemical
      staining, which results in unstained, white (Dlb-1a/Dlb-1-) ribbons on a stained
      background. Such ribbons are extremely rare in untreated C57BL mice which are
      homozygous for the dominant allele, as would be expected when two independent
      mutations are required. To test for LOH, we first treated the animals with a high
      dose of ethylnitrosourea (ENU) which induces many mutations and thus many
      heterozygous cells, and allowed 2 weeks for gene expression. Then the animals
      were treated with the test agent to determine if it could cause LOH and thus
      convert heterozygous mutant cells, which would not produce detectable ribbons,
      into homozygotes that would produce white, non-staining ribbons. Treatment with
      ENU alone produced a low, but detectable, frequency of mutant ribbons. Treatment
      with X-rays alone produced no detectable increase in the frequency of mutant
      ribbons. Combinations of these treatments produced additive effects, thus showing
      that no significant LOH was induced. The additivity of the two equal ENU
      treatments was unexpected, since double mutants should increase as the square of
      the mutant frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544750
TI  - Mimosine is a potent clastogen in primary and transformed hamster fibroblasts but
      not in primary or transformed human lymphocytes.
AB  - The cytogenetic effects of mimosine, a naturally occurring plant amino acid known
      to arrest cell-cycle progression at the G1-S border in cultured cells, have been
      studied. It was found that mimosine inhibits the cell-cycle progression in a dose
      dependent manner in primary and transformed Chinese hamster fibroblasts as well
      as primary lymphocytes and transformed lymphoblastoid cells of human origin. In
      the Chinese hamster fibroblast cells, the first division metaphases analysed were
      found to be highly damaged or pulverized. The damaged cells which could pass
      through the next cell division, showed very high frequencies of sister chromatid
      exchanges (SCEs) compared with untreated second division cells. No such
      cytogenetic alterations could be detected in the human cells. The absence of
      clastogenic effect in cells of lymphoid origin appears to be related to the known
      capacity of these cells to undergo apoptosis, thereby efficiently eliminating
      cells with high frequencies of chromosomal aberrations. Our study demonstrates
      the clastogenic potency of mimosine and suggests the need for a careful
      interpretation of the results while using mimosine for cellular or molecular
      studies pertaining to cell cycle events.

PMID- 8544751
TI  - Special considerations for conducting genotoxicity tests with protein materials.
AB  - Standard genotoxicity tests are often inappropriate for testing new biological
      entities, in particular for recombinant proteins which are nature-identical.
      Arguments that these may contain mutagenic impurities are not substantiated;
      however, we have produced evidence that such impurities would be detected amidst
      a vast excess of protein. Concerns that human patients receiving therapy may be
      at risk from higher-than-physiological levels of proteins are also somewhat
      theoretical. However, it is apparent that genotoxicity testing will be required
      for these products for the time being, even if pragmatic approaches reduce the
      battery of in vitro tests to Ames and chromosomal aberrations only, and reduce
      the top dose in vivo to 1000x the human therapeutic dose. There is a number of
      physical and chemical properties of proteins that demand special approaches to
      methodology if the tests are to produce accurate results. The potential for
      adsorption to certain forms of glass and plastic means special care must be taken
      in dissolving and diluting test solutions; adherence to filters means special low
      protein binding, non-pyrogenic filters should be used for sterilisation of test
      solutions, where this is necessary; freeze-dried powders aliquotted in multiple
      vials should be dissolved in minimal solvent and cascaded from vial to vial
      rather than trying to empty the solid contents for bulk weighing. As proteins are
      often supplied in solution, in order to achieve sufficiently high test
      concentrations, it may be necessary to resuspend test bacteria/cells in the test
      solutions for short periods of time before centrifuging and resuspending in
      selective or growth media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544752
TI  - T4 DNA ligase modulates chromosome damage induced by restriction endonucleases
      through an error-free process.
AB  - The possible modulation by T4 DNA ligase of the DNA double-strand breaks produced
      by restriction endonucleases in living mammalian cells was studied. A clear
      decrease in the frequency of chromosomal aberrations was observed when T4 DNA
      ligase was included in the electroporation treatment along with restriction
      enzymes inducing either cohesive- or blunt-ends in DNA. The relative proportions
      of exchange-type aberrations were similar for both kinds of treatments (with and
      without ligase), which seems to suggest an error-free ligation by T4 DNA ligase.

PMID- 8544753
TI  - The use of L5178Y mouse lymphoma cells to assess the mutagenic, clastogenic and
      aneugenic properties of chemicals.
AB  - Guidelines have been proposed to assess the potential of chemicals to affect
      human health. Written into these guidelines is the requirement that information
      be submitted on mutagenic activity. Although regulatory agencies accept
      mutagenicity data from both the hprt and tk loci in mammalian cells, many studies
      suggest that the L5178Y mouse lymphoma assay at the thymidine kinase locus is
      likely to detect a greater spectrum of mutagenic lesions. Thus, there is
      increasing emphasis being placed on this assay in many proposed and published
      guidelines. The L5178Y mouse lymphoma suspension protocol produces both small and
      large colonies which are the products of mutants growing at different rates.
      There is a reduction in the proportion of slowly growing mutants with respect to
      the total population of cells when expression is carried out in suspension. This
      potentially leads to quantitatively inaccurate assessments of the mutagenic
      activity of chemicals. Therefore an in situ procedure was developed that more
      accurately assesses the mutagenic activity of chemicals by maximizing the
      detection of small colonies. Many guidelines recommend tests that assess the
      clastogenic activity of chemicals. Some regulatory agencies accept data from the
      mouse lymphoma mutation assay to detect clastogens if the protocol is optimized
      for the detection of small colonies or if colony sizing data are submitted. The
      conventional suspension assay protocol is not sufficiently validated for this
      purpose. The in situ protocol has greater potential to meet these
      requirements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544754
TI  - Evaluation of modified bacterial mutagenicity assays for the genotoxicity testing
      of mineral oils.
AB  - A modified bacterial mutagenicity assay based on the Ames Salmonella/mammalian
      microsome test has been developed for application in the genotoxicity testing of
      mineral oils. The assay uses washed microsomes from rat liver in place of S9
      fraction in order to increase the sensitivity of detection of genotoxicity. The
      modified assay was used to test a series of oils for which skin carcinogenicity
      bioassay data in mice were available. Oils were tested as emulsions in water
      using Tween 80 as a dispersant. A mutagenicity index for each oil was obtained
      using non-linear regression analysis of data from the dose-response curve. The
      results showed an empirical correlation between increasing mutagenicity index,
      carcinogenicity and the polycyclic aromatic hydrocarbon content of the oils. The
      washed-microsome assay was also compared with modified Ames assays developed by
      Blackburn et al. (Cell Biol. Toxicol., 1, 40, 1984; Cell Biol. Toxicol., 2, 63,
      1986) which employed increased levels of S9 (rat and hamster liver) to test
      dimethyl sulphoxide extracts of oils. The washed-microsome assay can be used for
      the testing of whole oils rather than extracts which are necessary for the
      modified Ames assay. It is recognised that the determinants of carcinogenic
      activity in vivo include promoting activity which such assays are unable to
      detect. Nevertheless, such modified bacterial assays may be a useful prescreen
      since genotoxicity is recognised as a key initial step in carcinogenesis.

PMID- 8544755
TI  - Micronuclei induced by alachlor, mitomycin-C and vinblastine in human
      lymphocytes: presence of centromeres and kinetochores and influence of staining
      technique.
AB  - Antikinetochore antibodies and fluorescence in situ hybridization with an alphoid
      centromeric probe were applied to the cytokinesis-block micronucleus (MN) assay
      to study the suitability of these methodologies to detect clastogenic/aneugenic
      activity in isolated human lymphocytes. The chemicals selected for this study
      were the herbicide alachlor, the clastogen mitomycin-C (MMC), and the aneugen
      vinblastine sulphate (VBL). Furthermore, MN frequencies obtained from slides
      stained with May-Grunwald-Giemsa (MGG) and with the DNA fluorochrome 4',6'
      diamidino-2-phenylindole (DAPI) were compared to check if the DNA-specific DAPI
      facilitated a more accurate recording of MN than the unspecific MGG. The results
      showed that the detection of kinetochores (KC) or centromeres (CM) within MN are
      equally reliable and sensitive techniques to study the mode of action of
      clastogenic and aneugenic agents. The comparison of CM and KC detection in
      control cultures suggested that up to 17% of spontaneous chromosome-containing MN
      may be due to KC disruption, whereas the majority are caused by dysfunction in
      other components of the mitotic apparatus. Alachlor (7.5-20 micrograms/ml) and
      MMC (0.6 microM) acted as pure clastogens without aneugenic activity, inducing
      exclusively KC- and CM-negative MN. VBL produced primarily KC- and CM-positive
      MN, in accordance with its known mechanism of action. A comparison between CM and
      KC data in the VBL treatment suggested that some 7% of KC-containing MN may not
      be detected by the probe. The frequencies of MN were generally higher in slides
      stained with DAPI than in those stained with MGG, especially in controls and
      clastogen-treated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544756
TI  - A correlation of Salmonella mutagenicity with DNA adducts induced by the cooked
      food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
AB  - The correlation of bacterial mutagenicity with DNA adducts from the heterocyclic
      amine cooked-food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
      was investigated in Salmonella typhimurium strains TA98 (uvrB deficient) and
      TA1978 (uvrB proficient). Bacterial cells were exposed to PhIP using a
      modification of the Ames/Salmonella microsuspension assay. Half of the cells,
      generated from a 90 min pre-incubation and washing, were plated for revertant
      formation while the remaining half was subjected to DNA adduct analysis via 32P
      postlabeling. In TA98, DNA adducts were detected at an RAL (relative adduct
      labeling) of 10 x 10(-7) and 21 x 10(-7) at PhIP concentrations of 5.5 and 17
      microM, respectively. This corresponded to 28.8 and 20.9 adducts/revertant,
      respectively. These values were based on the assumption that only four repeating
      GC bases within a 75 DNA base region is the gene target site for PhIP induced
      mutations. In TA1978, no revertants above background were detected at any
      concentration of PhIP tested. DNA adducts, however, were detected at 11 x 10(-7)
      and 21 x 10(-7) adducts per nucleotide at 223 and 1116 microM PhIP, respectively.
      The lack of detectable revertants, but the presence of DNA adducts, suggests pre
      mutational lesions did occur during the 90 min pre-incubation. Presumably, when
      the S9 activating system and PhIP were removed (via washing with phosphate
      buffered saline) prior to plating, the cells containing an intact uvrB repair
      system repaired the lesions during the incubation time on the plates. In
      conclusion, the induction of revertants by adducts appears quite efficient, as
      approximately 25 adducts are required for one mutational event in the excision
      repair deficient bacteria.

PMID- 8544757
TI  - A new mutagenicity assay method for frameshift mutagens based on deleting or
      inserting a guanosine nucleotide in the beta-lactamase gene.
AB  - The conventional method of site-directed mutagenesis was used to develop two
      Salmonella strains, JK-1 and JK-2, for detecting frameshift mutagens. The JK-1
      strain was derived from Salmonella typhimurium TA1537 strain transformed by a
      mutant construct. A guanosine nucleotide was inserted between nucleotide residues
      312 and 313 of the beta-lactamase gene. The JK-2 strain was obtained by the same
      procedure, but a guanosine nucleotide in position 315 of the beta-lactamase gene
      was deleted. The strains were tested with ten frameshift mutagens and the
      revertants were selected by ampicillin resistance. Representative mutagens
      including 2-nitrofluorene (2-NF), 2-acetylaminofluorene (AAF), 9-aminoacridine (9
      AA), 2,7-diaminofluorene (2,7-DAF) and 2-methoxy-6-chloro-9-(3-(ethyl-2-chloro
      ethyl)-aminopropylamino)acridine (ICR-170) were more potent in the JK-1 strain
      than the JK-2 strain, and the number of revertant colonies were dose related.
      Under the same conditions, the ampicillin test was more sensitive than the Ames
      test. Other types of compounds such as 2-methoxy-6-chloro-9-(2
      chloroethylaminopropylamino)acridine (ICR-191), benzo[a]pyrene (BP), 4
      nitroquinoline N-oxide (4-NQNO), hycanthone and aflatoxin B1 (AFB1) were not as
      mutagenic to these new strains. The method is quite promising for studying
      certain specific frameshift mutagens, but more chemical mutagens should be tested
      to validate its applicability and reproducibility in general use.

PMID- 8544758
TI  - Micronucleus frequencies in lymphoblastoid cell lines measured with the
      cytokinesis-block technique and flow cytometry.
AB  - In these experiments, the cytokinesis-block technique was used to measure the
      spontaneous and radiation-induced micronucleus frequencies in lymphoblastoid cell
      lines from normal individuals and individuals with radiation-sensitive syndromes.
      The radiation-induced micronucleus frequencies were measured at different harvest
      times to investigate the optimum time to measure radiation-induced cytogenetic
      damage with the cytokinesis-block technique. The frequency of radiation-induced
      micronuclei was found to be independent of the frequency of binucleate cells in
      these cell lines. Longer incubation times were complicated by increasing numbers
      of mononucleate and multinucleate cells, and scoring slides at an early
      incubation time after the maximum frequency of binucleate cells is reached was
      recommended. Two of the cell lines (one established from an individual with
      ataxia telangiectasia, and one from an infant with mitotic instability) had
      significantly higher radiation-induced micronucleus frequencies than the control
      cell lines. Finally, the radiation-induced micronucleus frequencies in three of
      the cell lines were measured by flow cytometry, and the results ranked the cell
      lines in the same order of radiosensitivity as the cytokinesis block technique.

PMID- 8544759
TI  - The use of a streamlined bacterial mutagenicity assay, the MINISCREEN.
AB  - A streamlined bacterial mutagenicity assay, the MINISCREEN, was developed to
      enable the rapid screening of a large number of chemical compounds on a purely
      qualitative basis. Experiments with a series of known carcinogens/mutagens and
      non-carcinogens/mutagens showed a good correlation with conventional bacterial
      mutagenicity assays (Ames tests), and the subsequent testing of over 300
      candidate agricultural chemicals and over 100 industrial chemicals has proven its
      value as a screening method.

PMID- 8544760
TI  - Absence of evidence for mutagenicity of alcoholic beverages: an analysis of hprt
      mutant frequencies in 153 normal humans.
AB  - A substantial database on hprt mutant frequency in circulating T-cells derived
      from 153 normal humans was analysed to determine if any effect of alcohol
      consumption could be detected. Alcohol intake (as reported in a questionnaire
      completed at the time of the blood sample) ranged from 0 to 35+ units per week.
      Donors were classified into four groups, including total abstainers (n = 18);
      those who consumed less than the Royal College of Physicians guideline (men, 21
      units; women, 14 units) (n = 113); those who consumed more than the guideline
      value (n = 12); and designated alcohol-dependent subjects (n = 10). No
      significant difference in mutant frequency between the four groups was found, nor
      was an overall correlation between alcohol consumption and mutant frequency seen.

PMID- 8544761
TI  - Photochemical production of double-strand breaks in cellular DNA.
AB  - In a recent publication we described a novel route for the introduction of DNA
      double-strand breaks (DSBs) into cellular DNA. This involved the labelling of
      cellular DNA with bromodeoxyuridine (BrdU) and exposure to UVA light in the
      presence of Hoechst dye No. 33258. Here, we report an extension of that work to
      the use of iododeoxyuridine (IdU); cells substituted with known levels of IdU
      were subjected to a similar photolysis treatment and analyzed for strand breaks
      by elution assays. Results indicate that both single-strand breaks (SSBs) and
      DSBs depend linearly on the level of IdU substitution and fluence of UVA light.
      The yields of SSBs and DSBs were found to be 3.5 x 10(-5) and 9.5 x 10(-7)/IdU
      moiety/kJm-2, respectively. These results indicate that approximately 15-fold
      less SSBs and 5-fold less DSBs are produced per IdU than per BrdU moiety.

PMID- 8544762
TI  - Sister chromatid exchanges in cells defective in mismatch, post-replication and
      excision repair.
AB  - Three processes associated with DNA damage and genomic instability have been
      defined experimentally as operating during or soon after DNA replication:
      mismatch repair, post-replication repair and sister chromatid exchange. All these
      processes appear to operate on damage and/or errors in newly replicated DNA. Both
      mismatch repair and post-replication repair involve resynthesis of up to 1 kb of
      newly synthesized DNA: mismatch repair operates on single-base or slippage
      errors; post-replication repair operates on persistent gaps in newly synthesized
      DNA caused by damage on parental strands. Using colon cancer cells with different
      mismatch repair capacity, together with normal cells and excision-repair
      defective and post-replication-repair-defective xeroderma pigmentosum (XP) cells,
      we analysed possible interactions between these processes. No evidence for
      overlap of mismatch repair with excision or post-replication repair was found.
      However, post-replication-repair-defective XP variant cells that were SV40
      transformed showed higher UV-induced sister chromatid exchange frequencies than
      did untransformed cells. This suggests that sister chromatid exchanges in the XP
      variant are closely involved with UV-induced replication errors that are enhanced
      by transformation.

PMID- 8544763
TI  - Growth rate effects of mutations conferring streptomycin-dependence and of
      ancillary mutations in the rpsL gene of Escherichia coli: implications for the
      clustering (hypermutation) hypothesis for spontaneous mutation.
AB  - Colonies of newly arising streptomycin-dependent (SmD) mutants frequently contain
      a high proportion of cells with additional mutations (ancillary mutations) in the
      same gene (rpsL). The ancillary mutations appear to have arisen at a rate greatly
      above expectation. To better estimate this rate it is necessary to allow for any
      selective advantage conferred by the ancillary mutations. We have previously
      measured their effect on growth rate of established SmD strains in the presence
      of streptomycin. In the present work a pair of single and double mutant alleles
      (rpsL832 and rpsL852 respectively) has been employed together with the wild-type
      allele to model the situation soon after such mutations first arise, i.e. when
      the cell still contains wild-type S12 protein (the rpsL gene product). When these
      alleles, under the control of an IPTG-inducible promoter and carried on a
      plasmid, were expressed in the presence of a chromosomal wild-type allele, the
      double mutant allele permitted much faster cell growth than the single mutant
      allele. In the presence of streptomycin, and with rpsL+ on a plasmid, bacteria
      with a double mutant chromosomal gene grew faster than those with a single mutant
      chromosomal gene. If these results can be extrapolated to a bacterial cell in
      which an SmD mutation has just occurred, the ancillary mutation should be able to
      confer a selective advantage during a limited period when wild-type S12 protein
      is still present, both in the absence and in the presence of
      streptomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544764
TI  - Dose-responses for the slowing of gastric emptying in a rodent model by glucagon
      like peptide (7-36) NH2, amylin, cholecystokinin, and other possible regulators
      of nutrient uptake.
AB  - Several peptides have been proposed as regulators of nutrient release from the
      stomach and subsequent uptake from the gut. Using a phenol red gavage method, we
      compared the potencies of subcutaneously preinjected amylin, glucagon-like
      peptide-1 (7-36)amide (GLP-1), cholecystokinin octapeptide (CCK-8), gastric
      inhibitory peptide (GIP), glucagon, and pancreatic peptide on slowing the release
      of an acaloric gel from rat stomach. The latter three peptides did not fully
      inhibit gastric emptying at subcutaneous doses up to 100 micrograms. Amylin, GLP
      1, and CCK-8 fully inhibited gastric emptying, with ED50s of 0.42 +/- 0.07, 6.1
      +/- 0.12, and 8.5 +/- 0.20 nmol/kg +/- SE of log, respectively.

PMID- 8544765
TI  - Effects of thyroid status on glucose cycling by isolated rat hepatocytes.
AB  - The effects of alterations in thyroid status on glucose metabolism have been
      investigated in rat hepatocytes. Addition of 10 or 40 mmol/L glucose induced
      increases in respiration rate that were significantly larger in cells from
      hyperthyroid rats than from hypothyroid animals. The responses of hepatocytes
      from euthyroid rats were intermediate. In cells from hyperthyroid rats, most of
      the increase occurred upon addition of 10 mmol/L glucose, with only a further
      small stimulation resulting when glucose concentration was increased to 40
      mmol/L. For a given glucose concentration, glycolytic rates, determined by
      measuring release of tritium from [6-3H]glucose, were comparable in all thyroid
      states. Studies with 10 mmol/L [2-3H]glucose showed that cycling between glucose
      6-phosphate and glucose was almost twofold higher in euthyroid and hyperthyroid
      states as compared with the hypothyroid state, although the magnitude of the
      increase in cycling rate was only approximately 0.2 mumol glucose.min-1.g-1. When
      40 mmol/L [2-3H]glucose was added, over 44% of the glucose that was
      phosphorylated to glucose-6-phosphate was cycled back to glucose, but this
      cycling was independent of thyroid status. Cycling between fructose-1,6
      bisphosphate and fructose-6-phosphate was negligible in all thyroid states. Rates
      of glycogen synthesis were comparable in hypothyroid and hyperthyroid states and
      slightly less than in the euthyroid state. Glycolytically formed pyruvate was
      cycled back to glucose in hepatocytes from hypothyroid, euthyroid, and
      hyperthyroid rats. During a 60-minute incubation period, cycling to glucose in
      the presence of 10 mmol/L or 40 mmol/L glucose was up to twofold higher in cells
      from euthyroid and hyperthyroid rats than in hepatocytes from hypothyroid
      animals. The measured increases in cycling rates induced by thyroid hormone were
      small and in theory could have been satisfied by a much smaller increase in
      respiration rate than was observed.

PMID- 8544766
TI  - Assessment of functional liver mass and plasma flow in acromegaly before and
      after long-term treatment with octreotide.
AB  - Functional liver mass and functional liver plasma flow (FLPF) were assessed in 11
      patients with clinical features of acromegaly by determining galactose
      elimination capacity (GEC) and extrarenal clearance of sorbitol, before and 5 to
      7 months after treatment with the long-acting somatostatin analog, octreotide
      (150 to 600 micrograms/d in three subcutaneous injections). Growth hormone (GH)
      and insulin-like growth factor-I (IGF-I) levels, as well as liver size by
      ultrasound, were also recorded. Baseline GEC was increased in every patient but
      one, for a mean of 0.78 +/- 0.10 g/min (normal, 0.53 +/- 0.07; P < .01). At
      reevaluation after 5 to 7 months of octreotide treatment, a significant reduction
      of GEC was observed (0.62 +/- 0.08 g/min, P < .001). Changes of GEC paralleled
      those of GH (38.6 +/- 34.4 v 11.7 +/- 15.2 micrograms/L, P < .01) and IGF-I (5.0
      +/- 1.7 v 2.7 +/- 2.2 U/ml, P < .001). Significant correlations were found
      between GEC and GH (r = .50, P < .05) and between GEC and IGF-I (r = .55, P <
      .01). FLPF, assessed by extrarenal clearance of sorbitol, was within the normal
      limit in all cases (0.98 +/- 0.19 v 0.97 +/- 0.12 L/min, NS) and remained normal
      after 5 to 7 months of octreotide treatment (0.99 +/- 0.11 L/min). Hepatic
      structure determined with ultrasonic scanning and conventional liver-function
      tests were basally normal in all patients, with a slight increase of liver volume
      in three cases. No change of biochemical and/or morphological features occurred
      during follow-up evaluation. The results support the hypothesis that GH and
      especially IGF-I enhance liver metabolic capacity; conversely, functional liver
      perfusion is largely independent of their actions. Our data also suggest that
      octreotide is unable to produce well-structured changes of liver circulation when
      administered long-term.

PMID- 8544767
TI  - Glucose-induced changes in activity and phosphorylation of the Na+/H+ exchanger,
      NHE-1, in vascular myocytes from Wistar-Kyoto and spontaneously hypertensive
      rats.
AB  - Increased Na+/H+ exchanger (NHE) activity has been demonstrated in cells from
      patients with hypertension and diabetic nephropathy. Vascular myocytes from the
      spontaneously hypertensive rat (SHR) also exhibit increased NHE activity as
      compared with cells from the normotensive Wistar Kyoto rat (WKY). The interaction
      of increased glucose concentrations with NHE activity is unclear. The effect of
      glucose on NHE activity, NHE-1 (isoform 1) protein expression, and
      phosphorylation of cultured vascular myocytes from these rat strains was thus
      investigated. NHE activity was determined fluorometrically with 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein (BCECF). A rabbit NHE-1-specific polyclonal
      antibody was used (1) to measure NHE-1 abundance in Western blots of cell
      extracts and (2) for immunoprecipitating 32P-labeled NHE-1. Cells from SHR
      exhibited increased NHE activity and NHE-1 phosphorylation as compared with cells
      from WKY, with similar NHE-1 protein content per cell. Incubation in 25 mmol.L-1
      glucose for 24 hours led to increased NHE activity only in WKY cultures, with no
      change in NHE-1 protein but a concomitantly reduced NHE-1 phosphorylation.
      Changes in NHE activity in WKY cells were reversed by inhibition of protein
      kinase C. Incubation of SHR cells with 25 mmol.L-1 glucose did not enhance the
      increased NHE activity or NHE-1 phosphorylation present in these cells. Thus,
      high glucose levels have disparate effects on NHE activity and NHE-1
      phosphorylation in cells from different rat strains. The glucose-induced increase
      in NHE-1 turnover number in WKY cells is not mediated by an increase in its
      direct phosphorylation, but is dependent on protein kinase C.

PMID- 8544768
TI  - Prevalence of essential fatty acid deficiency in patients with chronic
      gastrointestinal disorders.
AB  - Patients with chronic intestinal disorders causing malabsorption, nutritional
      losses through diarrhea, or catabolic illness would be expected to have essential
      fatty acid (EFA) deficiency (EFAD), but such deficiency has not been demonstrated
      in patients treated in accordance with the prevailing standard of care. We
      studied plasma fatty acid patterns of 56 reference or control subjects and 47
      patients with chronic intestinal disorders (mostly Crohn's disease) using high
      resolution capillary column gas-liquid chromatography. Patients exhibited a shift
      in fatty acid metabolism similar to that previously shown to be associated with
      EFAD. Compared with control subjects, patients had (1) decreased polyunsaturated
      fatty acid (PUFA) levels (43.7% v 50.4%, P < .0001), (2) increased
      monounsaturated fatty acid (MUFA) levels (25.8% v 22.0%, P < .0001), (3) higher
      ratios of mead (20:3 omega 9) to arachidonic (20:4 omega 6) acid (0.020 v 0.013,
      P < .04), and (4) lower concentrations of total (214 v 284 mg/dL, P < .01),
      saturated ([SFA] 63 v 75 mg/dL, P < .001), MUFA (56 v 63 mg/dL, P < .001), and
      PUFA (93 v 143 mg/dL, P < .001). Patients had metabolic shifts toward increased
      production of MUFA and an increased ratio of derivatives to precursors of omega 6
      fatty acids, shifts that occur when cells are EFA-deficient. More than 25% of the
      patients had biochemical evidence of EFAD according to at least one criterion.
      Optimal diagnosis requires a concurrent evaluation of concentrations of fatty
      acids in plasma and in lipoproteins (percent fatty acids). On indices of EFA
      status that depend on percents, ratios, or concentrations of fatty acids or on
      the production of abnormal fatty acids, the patients were between patients with
      severe whole-body EFAD and healthy subjects, a state referred to as absolute EFA
      insufficiency. Patients with chronic intestinal disease should be evaluated for
      likely EFA deficiencies and imbalances, and treated with substantial amounts of
      supplements rich in EFAs, such as oral vegetable and fish oils, or intravenous
      lipids if necessary.

PMID- 8544769
TI  - Rats with portal-caval vein transposition show hyperinsulinemia and insulin
      resistance.
AB  - To compare the metabolic effects of portal and systemic delivery of insulin, we
      used portal-caval transposition (PCT) in rats to provide total systemic diversion
      of splanchnic venous blood. PCT rats exhibited normal weight gain, liver
      histology, liver-function tests, glycosylated hemoglobin, arterial blood
      pressure, and hepatic blood flow. Mean liver weight relative to body weight was
      12% lower in PCT rats than in sham-operated control (CTR) rats 30 days following
      transposition. Indwelling venous catheters were established to facilitate
      metabolic studies in conscious, minimally restrained animals. Postabsorptive
      plasma glucose and C-peptide (CPEP) levels were similar in PCT and CTR rats;
      however, postabsorptive immunoreactive insulin (IRI) levels were elevated in PCT
      rats (67 +/- 3.1 v 49 +/- 3.5 pmol.L-1, P < .002, n = 11 v 11), as were
      postabsorptive plasma glucagon levels (570 +/- 67 v 240 +/- 11 ng.L-1, P < .001,
      n = 11 v 16) at similar body weights. The postabsorptive CPEP/IRI concentration
      ratio was lower in PCT than in CTR rats (4.0 +/- 0.3 v 6.0 +/- 0.6, P < .02),
      suggesting reduced hepatic extraction of insulin. Insulin sensitivity (IS),
      determined by minimal model analysis of frequently sampled intravenous glucose
      tolerance tests yielding the sensitivity index (SI), was reduced in PCT compared
      with CTR (61 +/- 5.6 v 86 +/- 9.0 (mumol.L-1)-1.min-1, P < .04, n = 9 v 10).
      During euglycemic-hyperinsulinemic clamps, glucose infusion rates (GIRs) from 60
      to 120 minutes were lower in PCT than in CTR rats (6.0 +/- 0.3 v 8.0 +/- 0.4 g.kg
      1.min-1, P < .002, n = 9 v 7) with matching plasma IRI levels, confirming the
      reduced IS in PCT rats. Areas under the concentration curves ([AUCs] 0 to 150
      minutes) for glucose tolerance tests (gavage) indicated that plasma glucose
      excursion was similar in PCT and CTR rats whereas AUC IRI was significantly
      higher in PCT than in CTR rats (23 +/- 1.3 v 18 +/- 0.6 nmol.L-1.min, P < .009, n
      = 11 v 11). However, AUC CPEP for oral glucose tolerance tests was lower in PCT
      than in CTR rats (55 +/- 3.4 v 68 +/- 4.8 nmol.L-1.min, P < .05), indicating
      decreased insulin secretion. Thus, the mean ratio AUC CPEP/AUC IRI was
      significantly lower in PCT rats (2.5 +/- 0.2 v 3.8 +/- 0.3, P < .002), again
      suggesting reduced hepatic extraction of insulin. Thus, euglycemia after PCT was
      accompanied by elevated postabsorptive and glucose-stimulated levels of IRI in
      systemic blood, postabsorptive hyperglucagonemia, and decreased insulin secretion
      in response to glucose challenge (gavage), with diminished hepatic extraction of
      insulin and decreased IS. The PCT model illustrates the insulin-resistant
      adaptive state that results from systemic delivery of insulin, and indicates the
      importance of hepatic portal delivery of insulin and possibly of other
      gastroenteropancreatic hormones in the maintenance of IS and physiological
      metabolic control.

PMID- 8544770
TI  - Intravenous gamma-glutamyl-tyrosine elevates brain tyrosine but not catecholamine
      concentrations in normal rats.
AB  - A number of clinical situations may benefit from intravenous supplements of
      tyrosine (Tyr). In total parenteral nutrition (TPN), the supply of Tyr is limited
      by its poor solubility. In both rats and infants maintained on pediatric TPN,
      plasma Tyr levels are approximately 30% of normal, and in rat brains Tyr
      concentrations are similarly reduced. We reported previously that supplementing a
      TPN solution with the soluble peptide, gamma-glutamyl-Tyr [Glu(Tyr)], normalizes
      plasma Tyr and doubles brain Tyr in rats. To assess more fully the behavior of
      intravenous Glu(Tyr) in vivo, 20 mmol/L Glu(Tyr) was infused into the inferior
      vena cava of rats at rates increased every 2 hours over an 8-hour period (300 to
      450 mumol Glu(Tyr)/kg body weight/h). The surgical procedure for catheterization
      is described. At the maximum rate of infusion, plasma Tyr and Glu(Tyr)
      concentrations reached mean plateau values of 326 and 252 mumol/L, respectively.
      Brain Tyr concentrations were 71 and 264 nmol/g wet weight in control rats
      infused with heparinized saline (SAL group) and rats infused with Glu(Tyr) (PEP
      group) respectively. No differences were found in concentrations of
      norepinephrine (NE), dopamine (DA), or homovanillic acid (HVA) in prefrontal
      cortex (PFC), striatum (STR), or remaining brain (RB) tissue in PEP and SAL rats.
      We did not detect undergraded Glu(Tyr) in the brain, and less than 0.5% of
      infused Glu(Tyr) appeared in the urine.

PMID- 8544771
TI  - Hyperhomocysteinemia following a methionine load in patients with non-insulin
      dependent diabetes mellitus and macrovascular disease.
AB  - In the setting of an outpatient diabetic clinic, we determined whether
      macrovascular disease in patients with diabetes mellitus is associated with
      hyperhomocysteinemia (elevated plasma homocysteine [H(e)] concentrations)
      following a methionine load. Methionine-load tests were performed in 18 healthy
      controls, 11 diabetics without vascular disease (five insulin-dependent [IDDM]
      and six non-insulin-dependent [NIDDM]); and 17 diabetics with vascular disease
      (five IDDM and 12 NIDDM). All subjects were male, and there was no significant
      difference in mean age among the three groups. We measured plasma H(e)
      concentrations before and 2, 4, 6, 8, and 24 hours after an oral methionine load.
      Hyperhomocysteinemia (peak plasma H(e) concentration > control mean +/- 2 SD)
      occurred with significantly greater frequency (seven of 18, 39%) in patients with
      NIDDM as compared with age-matched controls (7%), being more common in those with
      macrovascular disease (five of 12, 41%). The area under the curve (AUC) over 24
      hours, reflecting the total period of exposure to H(e), was also elevated with
      greater frequency in patients with NIDDM and macrovascular disease (33%) as
      compared with controls (0%). We conclude that hyperhomocysteinemia is associated
      with macrovascular disease in a significant proportion of patients with NIDDM.
      Further investigation of this association may determine whether
      hyperhomocysteinemia contributes to the increased frequency and accelerated
      clinical course of vascular disease in patients with diabetes mellitus.

PMID- 8544773
TI  - Influence of sepsis and endotoxemia on polyamine metabolism in mucosa of small
      intestine in rats.
AB  - We examined the influence of sepsis and endotoxemia in rats on the biosynthesis
      of polyamines in small-intestinal mucosa. Sepsis was induced by cecal ligation
      and puncture (CLP); control rats were sham-operated. In other experiments, rats
      were treated with two subcutaneous injections of endotoxin (1 mg/kg) or
      corresponding injections of sterile saline. Ornithine decarboxylase (ODC) and S
      adenosylmethionine decarboxylase (SAMDC) activities and concentrations of
      putrescine, spermidine, and spermine were measured in jejunal mucosa at intervals
      during 16 hours. Sepsis stimulated ODC and SAMDC activities and increased
      putrescine and spermidine concentrations in jejunal mucosa. Injection of
      endotoxin resulted in metabolic changes similar to those observed following CLP.
      The results suggest that sepsis and endotoxemia stimulate polyamine biosynthesis
      in mucosa of small intestine. The role of polyamines in the regulation of cell
      proliferation and metabolic changes in the intestinal mucosa during sepsis
      remains to be determined.

PMID- 8544772
TI  - Effects of a long-acting gonadotropin-releasing hormone analog on the pituitary
      ovarian-adrenal axis in women with severe hirsutism.
AB  - We evaluated modifications in the pituitary-ovarian-adrenal axis in severely
      hirsute women after administration of the gonadotropin-releasing hormone analog
      (GnRHa), D-Trp-6-luteinizing hormone-releasing hormone (LHRH) (Triptorelin) in a
      prospective study at a tertiary hospital. A total of 20 hirsute women aged 19 to
      38 years were included. Hyperandrogenism of adrenal origin was excluded in all
      subjects. Patients received 3.75 mg D-Trp-6-LHRH intramuscularly (Decapeptyl
      3.75; Lasa-Ipsen, Barcelona, Spain). Serum levels of follicle-stimulating hormone
      (FSH), LH, estradiol (E2), prolactin (PRL), testosterone (T), androstenedione
      (delta 4 An), dehydroepiandrosterone sulfate (DHEAS), 17-OH-progesterone (17
      OHP), and sex hormone-binding globulin (SHBG) were determined before GnRHa
      administration, 24 and 48 hours after, and on days 7, 15, 30, and 45. GnRHa
      suppresses FSH, LH, and E2 in all women. Unexpectedly, adrenal steroids showed a
      flare-up phenomenon in the first days and subsequent decrease to lower values
      than before GnRHa administration. SHBG showed slight changes. After GnRHa,
      patients showed a significant decrease in T and delta 4 An: these hormones were
      reduced to half the basal levels. We conclude that GnRHa can potentially be used
      in the treatment of hyperandrogenism to reduce androgen levels in hirsute women.

PMID- 8544775
TI  - Metabolism of plasma lipoproteins in the genetically hypercholesterolemic rat
      (RICO).
AB  - Experiments were performed to determine the turnover processes of plasma
      cholesterol in genetically hypercholesterolemic rats (RICO). Specific activity of
      plasma cholesterol was monitored during 4 months following an intravenous
      injection of tritiated cholesterol. The results were subjected to two-pool model
      analysis. Cholesterol production in the RICO rat was significantly higher (28.9
      +/- 1.7 mg/d) than in the SW control (18.5 +/- 0.7, P < .01). The study also
      revealed a 30% decrease in the rate constant for cholesterol movement from the
      plasma toward the majority of organs in the RICO rat versus the SW control. Very
      low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density
      lipoprotein (HDL) turnover were investigated following injection of labeled
      lipoproteins (on cholesteryl ester or apolipoproteins). Results from these
      experiments showed that the higher HDL cholesterol concentration in the RICO rat
      as compared with the control is due to the greater production rate of esterified
      cholesterol in these lipoproteins (1.3 +/- 0.05 mg/h v 0.8 +/- 0.03 in the
      control, P < .001). The fractional catabolic rate (FCR) or production rate for
      VLDL were not significantly different between the two groups (3.4 +/- 0.01 and
      3.6 +/- 0.01 h-1 and 2.6 +/- 0.4 and 3.3 +/- 0.1 mg/h, respectively). However,
      radioactivity of VLDL recovered in LDL at death was considerably higher in RICO
      rats (14% +/- 1% v 6% +/- 1%, P < .01). The greater concentration of LDL
      cholesterol in RICO rats is due to a higher LDL production (0.40 +/- 0.05 v 0.19
      +/- 0.03 mg/h, P < .01) together with a lower catabolism (FCR, 5.5 +/- 0.6 v 7.9
      +/- 0.8%/h, P < .05). Cross-injection experiments showed that this lower
      catabolism of LDL is partly due to the nature of the lipoprotein particle. Taken
      together, these data are consistent with the hypothesis of a reduced uptake of
      apolipoprotein (apo)E-containing lipoproteins (VLDL and LDL), which results in a
      higher LDL cholesterol concentration in RICO rats.

PMID- 8544774
TI  - Biological effects of human growth hormone in rat adipocyte precursor cells and
      newly differentiated adipocytes in primary culture.
AB  - The effects of human growth hormone (hGH) on proliferation and differentiation of
      primary adipocyte precursor cells isolated from rat epididymal fat pads were
      studied under serum-free culture conditions. hGH markedly reduced the formation
      of new fat cells and the expression of glycerophosphate dehydrogenase activity, a
      marker enzyme of adipose differentiation, in a dose-dependent manner. To find an
      explanation for this inhibitory effect, we investigated the action of GH on (1)
      cell proliferation and on (2) lipid accumulation, the latter in the absence and
      presence of corticosterone. In undifferentiated cells, 5 nmol/L hGH increased
      both cell number and [3H]-thymidine incorporation (1.3- and 2.6-fold over basal,
      respectively). This effect was mediated by insulin-like growth factor-I (IGF-I),
      since hGH stimulated IGF-I production in undifferentiated cells by 12-fold and
      addition of an anti-IGF-I monoclonal antibody (IGF-I MAb) abolished the mitogenic
      effect of hGH but did not prevent hGH-induced suppression of adipose
      differentiation. In developing fat cells, hGH significantly reduced cellular 2
      deoxyglucose uptake and glucose incorporation into lipids. In addition, hGH
      exhibited a lipolytic action in the presence of insulin and triiodothyronine.
      These effects were not prevented by IGF-I MAb. Specific binding of [125I]-hGH to
      precursor cells increased significantly during adipose conversion. In
      differentiated cells Scatchard analysis yielded linear plots with an apparent Kd
      of 0.16 nmol/L and 8,400 sites per cell. Taken together, these data show that hGH
      reduces adipose conversion in primary cultures of rat adipocyte precursor cells
      while promoting cell proliferation through an increase in IGF-I production.

PMID- 8544777
TI  - Antioxidant defense system in lung of male and female rats: interactions with
      alcohol, copper, and type of dietary carbohydrate.
AB  - Male and female rats were used to investigate the effects of type of dietary
      carbohydrate (CHO), copper, and ethanol consumption on lung antioxidant enzyme
      activities and levels of phosphorylated compounds in whole blood. Copper
      deficient female rats exhibited a greater degree of copper deficiency than males,
      as assessed by hepatic copper concentration and hepatic copper superoxide
      dismutase (CuSOD) activity. However, copper-deficient male rats fed fructose
      containing diets exhibited greater growth retardation, anemia, and heart
      hypertrophy than females consuming the same diets and males fed starch. In
      addition, one of 10 copper-deficient male rats that ate a fructose-based diet and
      drank water and one of 10 copper-deficient male rats that ate a starch-based diet
      and drank ethanol died. Copper-deficient, starch-fed males exhibited the highest
      activities of glutathione peroxidase (GSH-Px) and catalase as compared with
      fructose-fed rats. Ethanol consumption elevated the activities of GSH-Px and
      catalase. Copper-deficient female rats exhibited higher catalase but lower GSH-Px
      activities than males. It is suggested that in copper deficiency, the ability to
      increase antioxidant enzyme activities in rats consuming starch is greater than
      in rats consuming fructose. Rats fed starch are provided with a greater degree of
      protection against oxidative damage than rats fed fructose. In addition,
      polyphosphorylated compounds in blood were reduced in copper-deficient male rats
      that consumed fructose-based diets. This may impair supply of oxygen to tissues.

PMID- 8544776
TI  - Aging in women--the four-compartment model of body composition.
AB  - The four-compartment model of body composition was examined in 155 white women
      through measurement of total body carbon (TBC), nitrogen (TBN), calcium (TBCa),
      and water levels. The age (mean +/- SD) of the population was 51.4 +/- 13.5
      years, and values for the four compartments were as follows (in kilograms):
      protein 8.9 +/- 1.0, water 30.9 +/- 3.5, mineral 2.6 +/- 0.4, and fat 22.6 +/-
      7.3. There was a linear change with age for protein and water, whereas mineral
      and fat were curvilinear. These latter two compartments also showed differences
      in premenopausal and postmenopausal rates of change. Various models were fit to
      the data to adjust for body size and age. Each of the four compartments (mineral,
      water, fat, and protein) changed with age, with fat increasing and the other
      compartments declining. The equation, y = age + age2 + height + weight, fit the
      data as well as the other models. Equations are provided to assess body
      composition in populations with disorders of nutrition, as well as other
      illnesses, using height, weight, and age as covariates. Since this was a cross
      sectional study, longitudinal studies will have to be performed to confirm the
      accuracy of rates of change with age predicted with each compartment.

PMID- 8544778
TI  - Changes in phospholipid composition of blood cell membranes (erythrocyte,
      platelet, and polymorphonuclear) in different types of diabetes--clinical and
      biological correlations.
AB  - A variety of disorders of erythrocyte, platelet, and polymorphonuclear leukocyte
      (PMN) functions have been described in diabetes. The phospholipid composition of
      erythrocyte, platelet, and PMN membranes from controls and from type I and II
      diabetics was investigated in this study. Phospholipids were determined by
      densitometry using the molybdenum blue reagent. In diabetics, the relative
      abundance of phosphatidylethanolamine (PE) increased in all cell types studied,
      whereas those of sphingomyelin (Sph) and phosphatidylcholine (PC) were decreased
      in platelets and PMN. The percentage of phosphatidylserine (PS) was reduced in
      erythrocytes but increased in platelets. The level of Sph in PMN was
      significantly lower in type I than in type II diabetics. Moreover, the longer the
      duration of diabetes and the poorer the metabolic control, the greater the
      decrease in Sph. Rheological parameters, which reflect the behavior of red blood
      cells (RBC), were correlated with the alteration in PE/PS ratio in these cells.

PMID- 8544779
TI  - Postprandial lipoprotein metabolism in normotriglyceridemic non-insulin-dependent
      diabetic patients: influence of apolipoprotein E polymorphism.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is associated with postprandial
      lipoprotein clearance defects that are correlated with the fasting
      hypertriglyceridemia widely observed in NIDDM patients. The aim of this study was
      to determine if such postprandial disturbances are found in NIDDM patients
      strictly normotriglyceridemic in the fasting state, and if the apolipoprotein E
      (apo E) polymorphism influences postprandial metabolism of intestinally derived
      lipoproteins. The vitamin A-fat loading test was used in 18 normotriglyceridemic
      NIDDM patients and seven normotriglyceridemic obese controls, and postprandial
      triglyceride (TG) and retinyl palmitate (RP) concentrations were evaluated in
      total plasma, and in the chylomicron (Sf > 1,000) and nonchylomicron (Sf < 1,000)
      fractions isolated by ultracentrifugation. NIDDM patients exhibited an amplified
      response of both TG and RP as compared with obese controls in the three
      fractions. Incremental TG response to the oral fat load was strongly correlated
      with fasting TG level (r = .80, P < .0001) in the whole study population.
      Postprandial lipoprotein profiles were distinguished in NIDDM patients according
      to apo E phenotype: despite normal fasting TG levels in E3/3 (n = 6), E2/3 (n =
      6), and E3/4 (n = 6), postprandial RP response was twofold to threefold higher in
      E2/3 and E3/4 patients than in the common E3/3 phenotype. Contrasting lower
      postprandial TG increment and lower fasting and postprandial high-density
      lipoprotein (HDL) and HDL3 cholesterol levels were observed in E3/4 versus E3/3
      patients, possibly reflecting modifications in lipid content of the postprandial
      lipoproteins driven by a differential lipid transfer activity depending on apo E
      isoform. These data indicate an enhanced postprandial lipemia in
      normotriglyceridemic NIDDM patients, and demonstrate the influence of apo E
      polymorphism on their lipoprotein clearance. Postprandial alterations of
      lipoprotein remnants may thus accelerate atherogenesis even in
      normotriglyceridemic NIDDM patients.

PMID- 8544780
TI  - The impact of obesity on hormonal parameters in hirsute and nonhirsute women.
AB  - The influence of obesity on sex hormone-binding globulin (SHBG) and androgen
      concentrations in hirsute and nonhirsute women has been evaluated. The study was
      performed in 226 hirsute women (88 obese and 138 non-obese) classified as being
      affected by polycystic ovarian syndrome (PCOS) or by idiopathic hirsutism (IH)
      and in 100 nonhirsute control women ([C] 60 lean and 40 obese). SHBG, free
      testosterone (fT), androstenedione (A), estradiol (E2), dehydroepiandrosterone
      sulfate (DHEAS), and gonadotropin levels were measured during the first week of
      the menstrual cycle by radioimmunoassay (RIA). A significant negative correlation
      between SHBG and body mass index (BMI) was observed in PCOS, IH, and C women. In
      obese women--whether PCOS, IH, or C-fT levels were significantly higher and,
      conversely, SHBG levels were lower than in non-obese women. A negative
      correlation between SHBG and fT was evidenced in each group. Upper-body obesity
      was associated with lower SHBG and higher fT levels than lower-body obesity. In
      conclusion, obesity, particularly upper-body obesity, is associated with a
      reduction in SHBG and an increase in fT in both nonhirsute and hirsute women.

PMID- 8544781
TI  - Decreased cortical and increased cancellous bone in two children with primary
      hyperparathyroidism.
AB  - The basis for this study is two children with primary hyperparathyroidism (PHPT)
      who radiographically manifested both marked subperiosteal resorption and
      prominent osteosclerosis. We hypothesize that the parathyroid hormone (PTH)
      elevation not only increased osteoclastic resorption of cortical bone but also
      simultaneously enhanced cancellous bone formation, giving rise to osteosclerosis.
      In this report, we describe the changes in trabecular and cortical bone density,
      as measured by quantitative computed tomography (QCT), in these two young
      patients with severe PHPT, before and after removal of a parathyroid adenoma.
      Before surgery, the radiographic findings of subperiosteal resorption and
      osteosclerosis were associated with low cortical and high cancellous bone density
      values in both children. Within 1 week of surgery, both cortical and cancellous
      bone density values increased and serum concentrations of calcium and, to a
      lesser degree, phosphorus decreased due to the "hungry bone syndrome." Twelve
      weeks after parathyroidectomy, QCT bone density values and skeletal radiographs
      were normal in both patients. The findings suggest that in patients with severe
      PHPT, the catabolic effect of PTH on cortical bone may be associated with a
      simultaneous anabolic effect on cancellous bone, and PTH may cause a significant
      redistribution of bone mineral from cortical to cancellous bone.

PMID- 8544782
TI  - Effects of insulin on glucose turnover rates in vivo: isotope dilution versus
      constant specific activity technique.
AB  - The conventional isotope dilution technique was compared with the more accurate
      constant specific activity (SA) method at six different insulin levels. Paired
      euglycemic clamp studies were performed in 30 normal subjects (4-hour insulin
      infusion: 5, 10, 20, 40, 80, and 160 mU . m-2 . min-1) using primed-constant 3-3H
      glucose infusion and either conventional unlabeled glucose infusates (Cold-GINF)
      or labeled glucose infusates (Hot-GINF) to maintain constant SA. At all insulin
      levels, both glucose disappearance (Rd) and hepatic glucose production (HGP) were
      underestimated by the conventional technique, and errors during the first 2 hours
      correlated with glucose infusion rates (GIRs) (r = .93, P < .00001). During the
      second hour, mean underestimation of HGP varied from 20% +/- 9% to 84% +/- 16% of
      basal rates from low-dose to high-dose insulin infusion studies. During prolonged
      equilibration (3 to 4 hours), errors decreased but were still significant in the
      two low-dose insulin infusion protocols during the fourth hour. In conclusion,
      using the conventional isotope dilution technique, suppression of glucose
      production was overestimated and stimulation of glucose Rd was underestimated,
      and these errors were greater the higher the GIR. Thus, artifactually greater
      hepatic and smaller peripheral effects may have been assumed for factors or
      therapies that influence insulin sensitivity in previous studies using a
      conventional isotope dilution technique, and therefore, reevaluation of these
      issues may be relevant in future studies.

PMID- 8544783
TI  - Dexamethasone-induced impairment in skeletal muscle glucose transport is not
      reversed by inhibition of free fatty acid oxidation.
AB  - Our previous studies suggested a possible role for the glucose-free fatty acid
      (FFA) cycle, ie, preferential utilization of FFA by muscle at the expense of
      glucose, in dexamethasone (DEX)-induced insulin resistance. To determine whether
      this resistance could be reversed by inhibiting FFA utilization, we used
      etomoxir, a potent inhibitor of mitochondrial FFA oxidation. Male Sprague-Dawley
      rats were injected subcutaneously with 1 mg/kg DEX or the vehicle every other day
      for 10 days, and half of each group was administered 10 mg/kg etomoxir by gavage
      once per day and 1 hour before the experiment. As expected, etomoxir treatment
      increased serum FFA levels and inhibited FFA oxidation by diaphragm in vitro.
      Administration of etomoxir decreased serum glucose and insulin concentrations
      under basal conditions in both control and DEX-treated animals, implying enhanced
      insulin sensitivity. DEX treatment significantly increased endogenous glucose
      production and decreased whole-body glucose disposal, as well as 2-deoxyglucose
      (2-DG) uptake by skeletal muscle during euglycemic-hyperinsulinemic clamps.
      Administration of etomoxir led to small but significant increases in glucose
      disposal rates of both control (14%) and DEX (23%) groups, but had no effect on
      residual endogenous glucose production. Thus, DEX-induced insulin resistance was
      marginally ameliorated but not completely reversed by etomoxir. Depressed 2-DG
      uptake by individual muscle tissues observed in the present study in conjunction
      with the absence of free intracellular glucose in muscle tissue following glucose
      insulin infusion strongly suggests that the primary defect in glucose metabolism
      is at the level of transport. Neither overall abundance of the insulin-sensitive
      glucose transporter (GLUT-4) in skeletal muscle nor its distribution between
      intracellular stores and plasma membrane were modified by DEX treatment, either,
      under basal conditions or in response to acute insulin stimulus. These results
      suggest a defect(s) in the inherent activity of plasma membrane-bound GLUT-4 as
      the likely mechanism for DEX-induced insulin resistance.

PMID- 8544784
TI  - [Relationship between the synthesis of a new stress response component and
      bacterial cell metabolism].
AB  - Various stress factors (incubation with redox-cycling agents, ozonization, heat
      shock) that induced accumulation of 2-C-methyl-D-erythritol-2,4
      cyclopyrophosphate (MEC) were also shown to induce various alterations of the
      phospholipid composition in three microbial species: Corynebacterium
      ammoniagenes, Micrococcus luteus, and Staphylococcus aureus. The influence of
      adding 10 carbohydrates to the growth medium on MEC accumulation by C.
      ammoniagenes cells was tested. Only glucose and mannose exerted a pronounced
      stimulatory effect on the MEC synthesis under oxidative stress. The target of
      oxidative attack whose transformation causes MEC synthesis is suggested to be
      located near or on the bacterial cytoplasmic membrane.

PMID- 8544786
TI  - ['95 Heart Week].

PMID- 8544785
TI  - [Comparative characteristics of mutants of Bacillus thuringiensis subsp.
      Kurstaki].
AB  - A study of physiological and biochemical properties of 12 strains of Bacillus
      thuringiensis subsp. kurstaki was performed. The strains studied included natural
      isolates similar to the type strain in their properties, a Cry-Spo+ mutant, and
      also mutants assigned to C-1 or C-73 crystovar according to the properties of
      their parasporal crystals and the ability to hydrolyze esculin, generate acid
      from salicin, and exert urease activity. The crystals produced by C-1 crystovar
      cultures were three times larger than those formed by C-73 crystovar bacteria;
      their distinctive feature was pathogenicity for mosquito larvae, and their effect
      on other insects (gypsy moth and meadow moth) was on the average twofold greater
      than the effect of C-73 crystovar crystals. A study of the antibacterial action
      of delta-endotoxins of B. thuringiensis subsp. kurstaki allowed us to more
      clearly elucidate the reasons for the differences in biological activity of C-1
      and C-73 crystovars. Comparative analysis of the data obtained confirmed that the
      effect of delta-endotoxins, formed per unit volume of the culture liquid, on
      insects and microorganisms is an important characteristic of B. thuringiensis
      strains. Of all the strains studied, the Cry-Spo+ mutant was the most potent
      producer of proteases and lecithinase.

PMID- 8544787
TI  - [Skin as an immune organ].

PMID- 8544788
TI  - [Is abortion murder?].

PMID- 8544789
TI  - [Pruritus. Physiology, pathophysiology, clinical aspects and therapy].

PMID- 8544790
TI  - [Randomized controlled trials. Recommendations for improving methodology].

PMID- 8544791
TI  - [Folic acid in pregnancy].

PMID- 8544792
TI  - Drugs for sexually transmitted diseases.
AB  - Many infections can be transmitted during sexual contact. The text and tables
      that follow are limited to treatment of infections associated primarily with
      sexual transmission. The treatment of AIDS and related infections was discussed
      in a recent issue of the Medical Letter (volume 37, page 87, October 13, 1995).

PMID- 8544793
TI  - Itraconazole for onychomycosis.

PMID- 8544794
TI  - Rho (D) immune globulin i.v. for prevention of Rh isoimmunization and for
      treatment of ITP.

PMID- 8544795
TI  - Treatment of children with stage IV favorable histology Wilms tumor: a report
      from the National Wilms Tumor Study Group.
AB  - The purpose of this study was to evaluate the effect of the sequential addition
      of doxorubicin and cyclophosphamide to the combination of vincristine and
      actinomycin D on the relapse-free survival of children with stage IV/favorable
      histology Wilms tumor. We reviewed the clinical courses of all randomized
      patients from National Wilms Tumor Study (NWTS)-2 and 3 with stage IV/favorable
      histology (FH) Wilms tumor. We determined the four-year relapse-free survival
      percentage for patients treated on NWTS-2 with the combination of vincristine
      (VCR) and actinomycin D (AMD) with (regimen D) or without (regimen C) doxorubicin
      (DOX), and for patients treated on NWTS-3 with the combination of VCR+AMD+DOX
      with (regimen J) or without (regimen DD-RT) cyclophosphamide (CTX). All children
      received whole lung radiation therapy. The four-year relapse-free survival
      percentage for children with stage IV/FH Wilms tumor treated with regimen C was
      53.3%, compared to 57.7% for those treated with regimen D (P = 0.63). The four
      year relapse-free survival percentage for children with stage IV/FH Wilms tumor
      treated with regimen DD-RT was 79.0%, compared to 80.9% for those treated on
      regimen J (P = 0.79). The four-year relapse-free survival for children with lung
      metastases only treated with regimen D on NWTS-2 was significantly lower than
      that of children treated with the related regimen DD-RT on NWTS-3 (P = 0.03). We
      conclude that the addition of doxorubicin to the combination of vincristine and
      actinomycin D and pulmonary irradiation did not clearly improve the four-year
      relapse-free survival percentage of children with stage IV/FH Wilms tumor,
      although the benefit may have been masked by the greater frequency of death due
      to toxicity in NWTS-2. There was no evidence that the addition of CTX to the
      three-drug treatment regimen improved the four-year relapse-free survival
      percentage of children with stage IV/FH Wilms tumor. The data with only two drugs
      derived from NWTS-2 suggest that there is a population of children with stage
      IV/FH Wilms tumor who can be successfully treated without an anthracycline. The
      goal of future research will be to identify this subgroup at the time of initial
      diagnosis.

PMID- 8544796
TI  - Paediatric tumours in the adult population: the experience of the Royal Marsden
      Hospital 1974-1990.
AB  - Adult patients (greater than 18 years), referred to the Royal Marsden Hospital
      between 1974 and 1990 with embryonal tumours, have been reviewed. The aim of the
      study was to document the presentation, management and outcome for this group of
      patients and to compare these parameters with those of tumours of the same
      histology arising in the paediatric population. The study population consisted of
      15 patients with medulloblastoma, 15 with Ewing's sarcoma, three with
      neuroblastoma, seven with rhabdomyosarcoma and two with nephroblastoma. Actuarial
      survival, at 5 years, for adults with medulloblastoma was 80%, which compares
      very favourably with the outcome for children treated over the same time span. In
      addition, salvage therapy after relapse was in some cases successful. In the
      Ewing's sarcoma group the outcome was less favourable, with 5-year actuarial
      survival of 50%. This is disappointing in view of the lack of tumours with poor
      prognostic features and may be an area in which these tumours differ from those
      that arise in children. The number of patients with the diagnosis of
      neuroblastoma, rhabdomyosarcoma and Wilms' tumour was too small for statistical
      analysis and they are presented as case reports. Embryonal tumours arising in
      adults provide an opportunity to study clinical behaviour and biology from an
      extreme standpoint. This may provide useful information with regard to aetiology,
      natural history and treatment response. The establishment of registers facilitate
      the collection of relevant data and also offers the opportunity to improve the
      treatment received by patients with these rare tumours.

PMID- 8544797
TI  - Cardiorespiratory status after treatment for acute lymphoblastic leukemia.
AB  - The use of certain chemotherapeutic agents is associated with dose-related
      cardiotoxicity and, potentially, with restrictive lung disease. Therefore, we
      assessed the cardiopulmonary status and exercise capacity of 19 patients (pts;
      9M:10F) 1.1 to 7.1 years (mean 4.6 +/- 1.5 years) after successful treatment of
      acute lymphoblastic leukemia (ALL) with Dana Farber Cancer Institute protocols.
      As body mass and nutritional status may influence exercise capacity, we also
      evaluated their anthropometric status and the plasma levels of rapid turnover
      proteins. Seven pts designated as "standard risk for relapse" (SR) had received
      low cumulative doses of doxorubicin (50 +/- 21 mg/m2), while twelve pts at "high
      or very high risk for relapse" (HR/VHR) had received higher doses (349 +/- 16
      mg/m2). The evaluations included a questionnaire, anthropometric assessments,
      echocardiography, pulmonary function studies, exercise testing, and nutritional
      assays. Patients' data were compared with published normative data or with
      control values from our laboratories. In addition, we compared SR pt data with
      HR/VHR pt data. No pt had overt symptoms or signs of cardiorespiratory
      compromise. The pts had a higher percent of body fat than age-matched healthy
      controls (29.7 +/- 7.9% vs. 20 +/- 6%; P < 0.001). On echocardiography, cardiac
      systolic function was within normal limits in all. However, HR/VHR pts had lower
      left ventricular (LV) shortening fractions than SR pts (P < 0.05). LV filling
      velocity, indicative of diastolic function (the E/A ratio), was normal in most
      pts. Pulmonary function studies were normal. Exercise capacity was below
      predicted in most cases but heart rates at peak exercise and leg muscle function
      were within normal limits, suggesting a deconditioned state. Plasma levels of
      rapid turnover proteins were also normal. Despite lack of overt morbidity in our
      pt population, subtle abnormalities persist in cardiac function while pulmonary
      function is normal. Longitudinal studies will identify if further abnormalities
      or overt morbidity develop. In later years, continuing obesity and a sedentary
      state may contribute to clinically relevant heart disease.

PMID- 8544799
TI  - Mitoxantrone-containing regimen for treatment of childhood acute leukemia (AML)
      and analysis of prognostic factors: results of the EORTC Children Leukemia
      Cooperative Study 58872.
AB  - The objective of this study was to evaluate the feasibility, the toxicity and the
      efficiency of a BFM-like treatment protocol for acute nonlymphoblastic leukemia
      (ANLL) of children in which mitoxantrone was substituted for conventional
      anthracycline. The chemotherapy called for induction (mitoxantrone, cytosine
      arabinoside, etoposide), consolidation (mitoxantrone, cytosine arabinoside, 6
      thioguanine), followed by two intensification courses with cytosine arabinoside
      plus, respectively, mitoxantrone during the first and etoposide during the second
      courses. Maintenance therapy consisted of daily 6 thioguanine, four-weekly
      courses of cytosine arabinoside (s.c. daily during 4 days) and eight-weekly
      courses of mitoxantrone. The latter drug was pursued up to a total cumulative
      dose of 150 mg/sqm. Maintenance therapy was stopped at 2 years of diagnosis. Out
      of 108 patients, 84 (77%) achieved a complete remission, 10 died during induction
      of hemorrhage, sepsis or pulmonary infiltration by leukemic cells. A total of 32
      relapses occurred. The median follow-up was 3.5 years. Actuarial event-free
      survival, disease-free survival and overall survival at 3 years as 41%, 52%, 56%,
      respectively. These results compare favorably with most reported data, and
      cytogenetic findings appear to be the most important prognostic factor.

PMID- 8544798
TI  - Clinical characteristics and factors affecting growth in long-term survivors of
      cancer.
AB  - We evaluated clinical characteristics and growth in 51 (24 males) long-term
      survivors of childhood cancer (median follow up 12.7 years). Patients were
      shorter, had a higher proportion of body fat and higher systolic blood pressure
      than their controls. The change in relative height during treatment was -0.83
      standard deviation score (S.D.S.) in patients with cranial irradiation and -0.32
      S.D.S. in patients without cranial irradiation; the figures after treatment were 
      0.56 and 0.20 S.D.S., respectively. Half (r2 = 0.50) of the variation in growth
      retardation during therapy could be explained by the cumulative doses of 6
      mercaptopurine (6-MP) and vincristine and relative height at diagnosis. Cranial
      irradiation, increased relative height at diagnosis and young age at diagnosis
      were significant predictors of growth failure over the total observation period,
      explaining 43% of the variation. We conclude that long-term survivors of
      childhood cancer have impaired linear growth, increased body fat mass and
      elevated systolic blood pressure. Young children who are tall for their age at
      diagnosis and treated with cranial irradiation have the highest risk of impaired
      growth after the diagnosis. High doses of 6-MP seem to contribute significantly
      to growth retardation during therapy.

PMID- 8544800
TI  - Outcome in 43 children presenting with metastatic Ewing sarcoma: the St. Jude
      Children's Research Hospital experience, 1962 to 1992.
AB  - The purpose of this work was to review the St. Jude Children's Research Hospital
      experience of patients presenting with metastatic Ewing sarcoma over a 30-year
      period. Forty-three of 212 cases of Ewing sarcoma presented with metastases at
      diagnosis. These patients were analyzed to determine whether primary tumor site
      or size, metastatic site(s), or advances in therapy have had a positive impact on
      survival. The overall survival for our 43 patients was 35% (95% confidence
      intervals, 20% to 50%). Comparing patients treated prior to 1979 with those
      treated after 1979, the overall survival was significantly different (P =
      0.0002). Comparing overall survival between pelvic and non-pelvic primaries (P =
      0.24), among metastatic sites (P = 0.83), and between tumors measuring > 8 cm in
      diameter to tumors measuring < 8 cm in diameter (P = 0.12), no significant
      differences were observed. Approximately one-third of patients presenting with
      metastatic Ewing sarcoma may achieve long-term survival. Children with metastatic
      Ewing sarcoma may benefit from clinical trials which intensify the doses of
      doxorubicin, and the highly effective combination of ifosfamide/etoposide.

PMID- 8544801
TI  - Successful treatment of orbital rhabdomyosarcoma in two infants using
      chemotherapy alone.
AB  - Two infants, 2 months and 13 months of age, were found to have orbital embryonal
      rhabdomyosarcomas (ERMS). Because of the adversities associated with either
      surgical exenteration or curative doses of radiation therapy, they were treated
      with chemotherapy alone. They survive disease-free 5 and 9 years after diagnosis
      with excellent cosmesis and normal vision. This approach may be suitable for
      similarly small (< 2 cm in diameter) ERMS in other sites.

PMID- 8544802
TI  - Nodular regenerative hyperplasia of the liver: description of two cases.
AB  - Nodular regenerative hyperplasia (NRH) of the liver is a condition of unknown
      origin, rarely occurring in children, usually accidentally discovered, described
      in association with a variety of clinical conditions and drugs. Confusion with
      other types of hepatic masses may pose a problem and for this reason NRH is
      considered a "tumor-like lesion." Histologically it consists of single or
      multiple regenerative foci. Hepatic failure and rupture of the liver have been
      rarely described as complications in adults, and not in children, and malignant
      transformation has not been demonstrated. Neither surgical removal nor other
      treatment is needed. These features are described as they were found in two
      patients we encountered.

PMID- 8544803
TI  - Case report: pulmonary blastoma in children--response to chemotherapy.
AB  - Pulmonary blastoma (PB) is a rare primary malignancy of the lung, with about 54
      cases reported in children. The tumor consists of mesenchymal and epithelial
      components resembling the fetal lung. It has been treated primarily with surgery
      and the effect of combination chemotherapy has not been systematically
      investigated. A 15-year-old girl with PB with metastases to bone and regional
      lymph node, and high levels of alphafetoprotein, is reported. A preoperative
      combination chemotherapy consisting of cisplatinum, etoposide alternating with
      iphosphamide with mesna, vincristine and epirubicine resulted in an objective
      response that permitted subsequent safe surgical excision of the primary tumor.
      This intensive combination chemotherapy should be tested in the management of
      advanced PB in children, as initial therapy as well as an adjuvant to surgery.

PMID- 8544804
TI  - Primary pulmonary rhabdomyosarcoma in childhood: clinico-biologic features in two
      cases with review of the literature.
AB  - The cases of two children under three years of age with primary pulmonary
      rhabdomyosarcoma and no associated lung malformations are reported and a review
      of the literature is presented. In both, complete surgical removal of the tumor
      was performed and histologic examination revealed embryonal subtype. Flow
      cytometric assessment showed a tumor-cell diploid DNA content. Postoperative
      radio- and chemotherapy were carried out, but in spite of treatment both girls
      died because of disease progression, fourteen and nine months after diagnosis.
      The importance of associated cystic lung malformations and DNA content in
      predicting clinical outcome of primary pulmonary rhabdomyosarcoma is evaluated.

PMID- 8544806
TI  - Malignant peripheral neuroectodermal tumor in an infant with neurofibromatosis
      type 1.
AB  - A case of multifocal malignant peripheral neuroectodermal tumor (PNET) arising
      from a plexiform neurofibroma in a 4-month-old Chinese boy with neurofibromatosis
      type 1 (NF-1) is described. Cytogenetic culture demonstrated hypotriploid
      karyotype with an abnormal clone characterized by 59-60, XY, +2, +3, +6, +8, +8,
      +12, +i(13)(q10), +der(14)t(1;14)(q21;q32), +16, +19, +20, +mar[cp3] with no
      apparent abnormality of chromosome 17. The child was treated with combination
      chemotherapy comprising ifosphamide, vincristine and doxorubicin. Despite initial
      partial response the child finally died of tumor progression and pulmonary
      metastases 8 months after diagnosis. We believe this is the first reported case
      of PNET in a child with NF-1 and may support an association between these two
      disorders of neural crest origin.

PMID- 8544805
TI  - Neuroblastoma metastatic to brain.

PMID- 8544807
TI  - Interferon-alpha for neurofibromas.

PMID- 8544808
TI  - Trends in cancer screening--United States, 1987 and 1992.
AB  - Screening methods and programs are critical strategies for the early detection
      and timely treatment of some cancers. Established methods for early detection of
      cancer include mammography, clinical breast examination (CBE), the Papanicolaou
      (Pap) test, proctosigmoidoscopy, fecal occult blood test (FOBT), and digital
      rectal examination (DRE) (1-4). To examine changes in the reported use of
      selected cancer screening tests, the National Cancer Institute analyzed data from
      CDC's National Health Interview Survey (NHIS) for 1987 and 1992 to calculate
      rates of use and compared these rates with the national health objectives for the
      year 2000 (5). This analysis suggests that, although the use of these tests
      increased, substantial progress is needed to meet the objectives.

PMID- 8544809
TI  - State-specific rates of mental retardation--United States, 1993.
AB  - Mental retardation (MR) is the most common developmental disability and ranks
      first among chronic conditions causing major activity limitations among persons
      in the United States (1). National and state-specific surveillance to measure the
      prevalence of MR can assist in targeting areas of need and allocating resources.
      State-specific prevalences for MR can be determined by using data about persons
      who receive specialized services for MR through entitlement programs. To estimate
      state-specific prevalences of MR in 1993, data were analyzed from the U.S.
      Department of Education (DOE) for children with MR who were enrolled in special
      education programs and from the Social Security Administration (SSA) for adults
      with MR. This report summarizes the findings, which suggest substantial state
      specific variation in the prevalence of MR in the United States.

PMID- 8544810
TI  - Nutritional status of children participating in the Special Supplemental
      Nutrition Program for Women, Infants, and Children--United States, 1988-1991.
AB  - Recent increases in the prevalence of overweight among school-aged children (1)
      and adults (2) in the United States have prompted concern about an increase in
      overweight among preschool-aged children and a possible association with the
      foods provided by the Special Supplemental Nutrition Program for Women, Infants,
      and Children (WIC). To assess and compare weight status and nutrient intake among
      WIC participants and other low-income children, CDC analyzed data from phase 1 of
      the Third National Health and Nutrition Examination Survey (NHANES III), 1988
      1991. This report summarizes the results of this analysis, which indicate that
      foods provided by WIC are not associated with increased overweight among
      preschool-aged children.

PMID- 8544811
TI  - Injury surveillance in correctional facilities--Michigan, April 1994-March 1995.
AB  - Following an outbreak of Legionnaires disease in a Michigan prison in 1993 (1),
      which was first recognized at a civilian hospital, the Michigan Department of
      Public Health (MDPH) recommended that surveillance for acute infectious diseases
      be established in the Michigan Department of Corrections (MDOC). In April 1994,
      MDOC and MDPH implemented a pilot system to monitor trends and detect clusters of
      selected acute infectious diseases and injury in six Michigan state correctional
      facilities. This report summarizes the findings of injury surveillance during
      April 1994-March 1995.

PMID- 8544812
TI  - Molecular cloning and functional characterization of a cDNA encoding nucleosome
      assembly protein 1 (NAP-1) from soybean.
AB  - NAP-1, a protein first isolated from mammalian cells, can introduce supercoils
      into relaxed circular DNA in the presence of purified core histones. Based on its
      in vitro activity, it has been suggested that NAP-1 may be involved in nucleosome
      assembly in vivo. We isolated a cDNA clone encoding a soybean NAP-1 homolog, SNAP
      1. The SNAP-1 cDNA contains an open reading frame of 358 amino acids residues
      with a calculated molecular weight of 41 kDa. The deduced amino acid sequence of
      SNAP-1 shares sequence similarity with yeast NAP-1 (38%) and human hNRP (32%).
      Notable features of the deduced sequence are two extended acidic regions thought
      to be involved in histone binding. SNAP-1 expressed in Escherichia coli induces
      supercoiling in relaxed circular DNA, suggesting that SNAP-1 may have nucleosome
      assembly activity. The specific activity of SNAP-1 is comparable to that of HeLa
      NAP-1 in an in vitro assay. Western analysis reveals that SNAP-1 is expressed in
      the immature and young tissues that were examined, while mature tissues such as
      old leaves and roots, show very little or no expression. NAP-1 homologs also
      appear to be present in other plant species.

PMID- 8544813
TI  - SlyA, a regulatory protein from Salmonella typhimurium, induces a haemolytic and
      pore-forming protein in Escherichia coli.
AB  - A chromosomal fragment from Salmonella typhimurium, when cloned in Escherichia
      coli, generates a haemolytic phenotype. This fragment carries two genes, termed
      slyA and slyB. The expression of slyA is sufficient for the haemolytic phenotype.
      The haemolytic activity of E. coli carrying multiple copies of slyA is found
      mainly in the cytoplasm, with some in the periplasm of cells grown to stationary
      phase, but overexpression of SlyB, a 15 kDa lipoprotein probably located in the
      outer membrane, may lead to enhanced, albeit unspecific, release of the
      haemolytic activity into the medium. Polyclonal antibodies raised against a
      purified SlyA-HlyA fusion protein identified the overexpressed monomeric 17 kDa
      SlyA protein mainly in the cytoplasm of E. coli grown to stationary phase,
      although smaller amounts were also found in the periplasm and even in the culture
      supernatant. However, the anti-SlyA antibodies reacted with the SlyA protein in a
      periplasmic fraction that did not contain the haemolytic activity. Conversely,
      the periplasmic fraction exhibiting haemolytic activity did not contain the 17
      kDa SlyA protein. Furthermore, S. typhimurium transformed with multiple copies of
      the slyA gene did not show a haemolytic phenotype when grown in rich culture
      media, although the SlyA protein was expressed in amounts similar to those in the
      recombinant E. coli strain. These results indicate that SlyA is not itself a
      cytolysin but rather induces in E. coli (but not in S. typhimurium) the synthesis
      of an uncharacterised, haemolytically active protein which forms pores with a
      diameter of about 2.6 nm in an artificial lipid bilayer. The SlyA protein thus
      seems to represent a regulation factor in Salmonella, as is also suggested by the
      similarity of the SlyA protein to some other bacterial regulatory proteins. slyA-
      and slyB-related genes were also obtained by PCR from E. coli, Shigella sp. and
      Citrobacter diversus but not from several other gram-negative bacteria tested.

PMID- 8544814
TI  - Extension of the Rhizobium meliloti succinoglycan biosynthesis gene cluster:
      identification of the exsA gene encoding an ABC transporter protein, and the exsB
      gene which probably codes for a regulator of succinoglycan biosynthesis.
AB  - Two new genes, designated exsA and exsB, were identified adjacent to the 24 kb
      exo gene cluster of Rhizobium meliloti, which is involved in succinoglycan (EPS
      I) biosynthesis. The derived amino acid sequence of ExsA displayed significant
      homologies to ATP binding cassette (ABC) transporter proteins. R. meliloti
      strains mutated in exsA were characterized by a decreased ratio of HMW to LMW EPS
      I, indicating a function for ExsA in EPS I biosynthesis. The R. meliloti NdvA
      protein, which is involved in the transport of cyclic beta-(1,2)-glucans, was
      identified as the closest homologue of ExsA. R. meliloti exsB mutants produced a
      three-fold increased amount of EPS I in comparison to the wild-type strain. In
      contrast, high copy number of exsB resulted in a decrease in the EPS I level to
      20% of wild type, indicating that the exsB gene product can negatively influence
      EPS I biosynthesis. It was demonstrated that this influence is not due to
      transcriptional regulation of the exo genes by the exsB gene product. By plasmid
      integration it was shown that exsA and exsB represent monocistronic transcription
      units.

PMID- 8544815
TI  - Multicopy plasmid suppression of stationary phase chaperone toxicity in
      Escherichia coli by phosphogluconate dehydratase and the N-terminus of DnaK.
AB  - Overproduction of DnaK in Escherichia coli results in a bacteriocidal effect.
      This effect is most acute in stationary phase cells. A selection scheme was
      developed to isolate multicopy suppressors from an E. coli plasmid expression
      library, which overcome the stationary phase toxicity of excess DnaK. Two
      suppressor plasmids were recovered which contained inserts of 1.85 kb and 2.69
      kb, respectively. Rearranged and deleted plasmid derivatives were constructed and
      used to further localize the suppressors. DNA sequence analysis demonstrated that
      one suppressor encoded phosphogluconate dehydratase (Edd) while the other
      suppressor encoded the N-terminal 237 amino acids of DnaK itself (DnaK'). Strains
      bearing the suppressor plasmids constitutively overproduced proteins with
      apparent masses of 66 kDa (Edd) and 37 kDa (DnaK') as determined by gel
      electrophoresis. Western blot analysis using polyclonal antisera specific for
      either Edd or DnaK confirmed the identity of these overproduced proteins.
      Suppression of DnaK toxicity was eliminated by the introduction of a + 1
      frameshift mutation early in the respective coding regions of either of the two
      suppressors. These results suggest that suppressor gene translation plays a role
      in the mechanism of DnaK suppression.

PMID- 8544816
TI  - Nuclear genes required for post-translational steps in the biogenesis of the
      chloroplast cytochrome b6f complex in maize.
AB  - Nuclear genes essential for the biogenesis of the chloroplast cytochrome b6f
      complex were identified by mutations that cause the specific loss of the complex.
      We describe four transposon-induced maize mutants that lack cytochrome b6f
      proteins but contain normal levels of other photosynthetic complexes. The four
      mutations define two nuclear genes. To identify the step at which each mutation
      blocks protein accumulation, mRNAs encoding each subunit were examined by
      Northern hybridization analysis and the rates of subunit synthesis were examined
      in pulse-labeling experiments. In each mutant the mRNAs encoding the known
      subunits of the complex were normal in size and abundance and the major subunits
      were synthesized at normal rates. Thus, these mutations block the biogenesis of
      the cytochrome b6f complex at a post-translational step. The two nuclear genes
      identified by these mutations may encode previously unknown subunits, be involved
      in prosthetic group synthesis or attachment, or facilitate assembly of the
      complex. These mutations were also used to provide evidence for the authenticity
      of a proposed fifth subunit of the complex and to demonstrate a role for the
      cytochrome b6f complex in protecting photosystem II from light-induced
      degradation.

PMID- 8544817
TI  - Toxin A secretion in Pseudomonas aeruginosa: the role of the first 30 amino acids
      of the mature toxin.
AB  - Toxin A, one of several virulence factors secreted by the gram-negative bacterium
      Pseudomonas aeruginosa, is synthesized as a 71 kDa precursor with a typical
      prokaryotic leader peptide (LP), and is secreted as a 68 kDa mature protein.
      Evidence from a previous study suggested that a signal required for toxin A
      secretion in P. aeruginosa may reside within the region defined by the toxin A LP
      and the first 30 amino acids (aa) of mature toxin A. In the present study, we
      have used exonuclease Bal31 deletion analysis to examine the specific role of the
      first 30 aa in toxin A secretion. Four toxA subclones, which encode products
      containing the toxin A LP and different segments of the 30-residue region fused
      to a toxin A carboxy-terminal region, were identified. In addition, a gene fusion
      encoding a hybrid protein consisting of the LP of P. aeruginosa elastase and the
      final 305 residues of toxin A, was generated. The cellular location of the toxA
      subclone products in P. aeruginosa was determined by immunoblotting analysis.
      Toxin A CRMs (cross-reacting material) encoded by different subclones were
      detected in different fractions of P. aeruginosa including the periplasm and the
      supernatant. Results from these studies suggest that (1) mature toxin A contains
      two separate secretion signals one within the N-terminal region and one within
      the C-terminal region; and (2) the first 30 residues of the mature toxin A form
      part of the N-terminal secretion signal.

PMID- 8544818
TI  - Site-specific mutagenesis in Enterobacter agglomerans: construction of nif B
      mutants and analysis of the gene's structure and function.
AB  - A novel technique was developed which may be generally well suited to the site
      specific construction of mutations in Enterobacter agglomerans. The method is
      based on the observation that E. agglomerans can be cured of a plasmid of the
      incompatibility group IncQ by cultivation on citrate-containing medium. To test
      the applicability of this technique, we inserted a kanamycin cassette into the
      cloned nifB gene, transferred it into E. agglomerans, and selected for
      recombinants in which the wild-type nifB was replaced by the mutated gene by
      growing transformants on citrate medium with kanamycin. The nifB- mutants with
      the kanamycin cassette inserted in either orientation showed a nif- phenotype.
      Further, we determined the nucleotide sequence of nifB. A typical sigma 54
      dependent promoter and a consensus NifA binding site were found upstream of nifB.
      Activation of this promoter by both heterologous and homologous NifA proteins was
      observed in vivo. The predicted amino acid sequence of the NifB protein showed
      strong similarity to the NifB sequences of other diazotrophic bacteria. The
      typical clustering of cysteine residues at the N-terminal end indicates its
      involvement in Fe-Mo cofactor biosynthesis.

PMID- 8544819
TI  - Detection of point mutations in chloroplast genes of Antirrhinum majus L. I.
      Identification of a point mutation in the psaB gene of a photosystem I plastome
      mutant.
AB  - A point mutation in the plastome-encoded psaB gene of the mutant en:alba-1 of
      Antirrhinum majus L. was identified by an analysis of chloroplast DNA with a
      modified PCR-SSCP technique. Application of this technique is indicated when a
      gene or a group of genes is known in which the point mutation is located.
      Analysis of primary photosynthetic reactions in the yellowish white plastome
      mutant indicated a dysfunction of photosystem (PS) I. The peak wavelength of PS I
      dependent chlorophyll (Chl) fluorescence emission at 77 K was shifted by 4 nm to
      730 nm, as compared to fluorescence from wild-type. There were no redox
      transients of the reaction center Chl P700 upon illumination of leaves with
      continuous far-red light or with rate-saturating flashes of white light. The PS I
      reaction center proteins PsaA and PsaB are not detectable by SDS-PAGE in mutant
      plastids. Hence, plastome encoded PS I genes were regarded as putative sites of
      mutation. In order to identify plastome mutations we developed a modified SSCP
      (single-strand conformation polymorphism) procedure using a large PCR fragment
      which can be cleaved with various restriction enzymes. When DNA from wild-type
      and en:alba-1 was submitted to SSCP analysis, a single stranded HinfI fragment of
      a PCR product of the psaB gene showed differences in electrophoretic mobility.
      Sequence analysis revealed that the observed SSCP was caused by a single base
      substitution at codon 136 (TAT-->TAG) of the psaB gene. The point mutation
      produces a new stop codon that leads to a truncated PsaB protein. The results
      presented indicate that the mutation prevents the assembly of a functional PS I
      complex. The applicability to other plastome mutants of the new method for
      detection of point mutations is discussed.

PMID- 8544820
TI  - Characterization of an EcR/USP heterodimer target site that mediates ecdysone
      responsiveness of the Drosophila Lsp-2 gene.
AB  - The Larval serum protein-2 gene (Lsp-2) of Drosophila melanogaster is uniquely
      expressed in the fat body tissue from the beginning of the third instar to the
      end of adult life. Accumulation of the larval Lsp-2 transcript is enhanced by 20
      hydroxyecdysone. To study the molecular basis for ecdysone regulated Lsp-2
      activity, deletion mutants of the Lsp-2 5'-flanking region were constructed by
      fusion to either the Escherichia coli chloramphenicol acetyltransferase (CAT)
      gene or to an hsp70-lacZ hybrid gene encoding beta-galactosidase. Constructs
      transfected into Drosophila S2/M3 cells were shown to confer transient ecdysone
      inducibility on the reporter genes. A single functional ecdysone response element
      (EcRE) was localized at position -75 relative to the Lsp-2 transcription
      initiation site. In gel mobility shift assays using fat body nuclear extracts or
      nuclear receptors synthesized in vitro, a 27-bp sequence harboring the EcRE bound
      both the Drosophila ecdysone receptor and the Drosophila retinoid-X homologue,
      Ultraspiracle, in a cooperative manner. Competition experiments indicate that the
      affinity of the Lsp-2 EcRE for the ecdysone receptor complex is comparable to
      that of the canonical EcRE of the hsp27 gene and is at least 4-fold greater than
      that of Fbp1, another fat body-specific Drosophila gene. Our results suggest that
      structural features of this EcRE determine its ability to induce ecdysone
      responsiveness at a lower ligand concentration and may form the basis for
      differential hormone responsiveness within the fat body.

PMID- 8544821
TI  - Analysis of the regulation of the Aspergillus nidulans penicillin biosynthesis
      gene aat (penDE), which encodes acyl coenzyme A:6-aminopenicillanic acid
      acyltransferase.
AB  - The regulation of the Aspergillus nidulans penicillin biosynthesis gene aat
      (penDE), which encodes acyl coenzyme A:6-aminopenicillanic acid acyltransferase
      (AAT), was analysed. Major transcriptional start sites map within 100 nucleotides
      upstream from the aat initiation codon. To study the regulation of aat
      expression, various aat-lacZ gene fusions were constructed, in which the aat
      promoter region was fused in frame with the Escherichia coli lacZ reporter gene.
      A. nidulans strains carrying recombinant plasmids integrated as single copies at
      the chromosomal argB locus were identified. In both fermentation and minimal
      media, aat-lacZ expression was maximal during the first 24 h of a fermentation
      run. Compared with minimal medium, aat-lacZ expression was increased two-fold in
      fermentation medium. Although AAT specific activity was reduced in mycelia grown
      on glucose instead of lactose, expression of aat-lacZ gene fusions was not
      repressed on glucose, suggesting that the glucose effect is mediated
      posttranscriptionally. The effect of glucose on AAT activity was reversed by
      further incubation of glucose-grown mycelia on lactose. Neither the inclusion of
      the first intron of the aat gene in the aat-lacZ fusion integrated at the
      chromosomal argB locus, nor the disruption of the acvA gene had any regulatory
      effect on aat-lacZ expression. In the heterologous, nonpenicillin producer A.
      niger, basal expression of aat-lacZ gene fusions was observed at about the same
      level as in A. nidulans.

PMID- 8544823
TI  - Mutation frequency decline in Escherichia coli. I. Effects of defects in mismatch
      repair.
AB  - Mutation frequency decline (MFD) in Escherichia coli was examined for effects
      associated with genetic defects in mismatch repair. The kinetics of MFD are
      slower when the B/r strain WU3610 carries the mutation mutS201::Tn5 or
      mutL::Tn10, both of which affect mismatch repair. Similar slow kinetics are
      produced by mutH34 but not by mutH471::Tn5; the latter has no apparent effect.
      Strain WU3610-45 (mfd-1) produces the slower kinetics if transcription is
      inhibited during the post-UV incubation, although it produces no decline in
      normal circumstances. The slower kinetics are therefore attributed to bulk
      excision repair that remains when rapid transcription-coupled repair (TCR) is
      eliminated by certain defects in mismatch repair. A model is proposed wherein
      mismatch repair defects are thought to slow the activity of TCR but, unlike an
      mfd defect, not to impede dissociation of stalled transcription complexes at
      lesions in the transcribed DNA strand.

PMID- 8544822
TI  - Inactivation of the yeast Sen1 protein affects the localization of nucleolar
      proteins.
AB  - A mutation in the Saccharomyces cerevisiae SEN1 gene causes accumulation of end
      matured, intron-containing pre-tRNAs. Cells containing the thermosensitive sen1-1
      mutation exhibit reduced tRNA splicing endonuclease activity. However, Sen1p is
      not the catalytic subunit of this enzyme. We have used Sen1p-specific antibodies
      for cell fractionation studies and immunofluorescent microscopy and determined
      that Sen1p is a low abundance protein of about 239 kDa. It localizes to the
      nucleus with a granular distribution. We verified that a region in SEN1
      containing a putative nuclear localization signal sequence (NLS) is necessary for
      nuclear targeting. Furthermore, we found that inactivation of Sen1p by
      temperature shift of a strain carrying sen1-1 leads to mislocalization of two
      nucleolar proteins, Nop1 and Ssb1. Possible mechanisms are discussed for several
      related nuclear functions of Sen1p, including tRNA splicing and the maintenance
      of a normal crescent-shaped nucleolus.

PMID- 8544824
TI  - Mutation frequency decline in Escherichia coli. II. Kinetics support the
      involvement of transcription-coupled excision repair.
AB  - Mutation frequency decline (MFD) in Escherichia coli was examined to demonstrate
      repair of targeting photoproducts during the post-UV incubation required in this
      process. Repair of mutation-targeting cyclobutane pyrimidine dimers (T < > C) was
      demonstrated when a correlation was established between the mutation frequency
      normally associated with these lesions and the rate of mutation production at
      these lesions by spontaneous deamination of cytosines and photoreversal in ung
      defective cells. An incubation producing a decline in mutation frequency, i.e.,
      MFD, also produces lower rates of mutation increase via the deamination
      mechanism. Since the latter assay involves processes entirely within the post-UV
      incubation period, the lower rates are attributed to rapid transcription-coupled
      nucleotide excision repair (TCR) that reduces the number of relevant T < > C
      dimers during this period. Rediscovery of the neglected fact that MFD can be
      stimulated by post-UV incubation in buffer alone is part of the analysis. Results
      presented here and a variety of others are discussed to support a model of MFD as
      a particular example of TCR: effective repair of photoproducts in the transcribed
      DNA strand that target glutamine tRNA suppressor mutations occurs during the
      appropriate post-UV incubation and is responsible for MFD.

PMID- 8544825
TI  - Comparative mapping of the barley genome with male and female recombination
      derived, doubled haploid populations.
AB  - Male (anther culture) and female (Hordeum bulbosum) derived, doubled haploid
      populations were used to map the barley genome and thus determine the different
      recombination rates occurring during meiosis in the F1 hybrid donor plants. The
      anther culture-derived (male recombination) population showed an 18% overall
      increase in recombination rate. This increased recombination rate was observed
      for every chromosome and most of the chromosome arms. Examination of linkage
      distances between individual markers revealed eight segments with significantly
      higher recombination in the anther culture-derived population, and one in the
      Hordeum bulbosum-derived population. Very strong distortions of single locus
      segregations were observed in the anther culture-derived population, but map
      distances were not affected significantly by these distortions. There were 1.047
      and 0.912 recombinations per chromosome in the anther culture and Hordeum
      bulbosum-derived doubled haploid populations, respectively.

PMID- 8544826
TI  - Constitutive activation of the Saccharomyces cerevisiae mating response pathway
      by a MAP kinase kinase from Candida albicans.
AB  - The HST7 gene of Candida albicans encodes a protein with structural similarity to
      MAP kinase kinases. Expression of this gene in Saccharomyces cerevisiae
      complements disruption of the Ste7 MAP kinase kinase required for both mating in
      haploid cells and pseudohyphal growth in diploids. However, Hst7 expression does
      not complement loss of either the Pbs2 (Hog4) MAP kinase kinase required for
      response to high osmolarity, or loss of the Mkk1 and Mkk2 MAP kinase kinases
      required for proper cell wall biosynthesis. Intriguingly, HST7 acts as a
      hyperactive allele of STE7; expression of Hst7 activates the mating pathway even
      in the absence of upstream signaling components including the Ste7 regulator
      Ste11, elevates the basal level of the pheromone-inducible FUS1 gene, and
      amplifies the pseudohyphal growth response in diploid cells. Thus Hst7 appears to
      be at least partially independent of upstream activators or regulators, but
      selective in its activity on downstream target MAP kinases. Creation of Hst7/Ste7
      hybrid proteins revealed that the C-terminal two-thirds of Hst7, which contains
      the protein kinase domain, is sufficient to confer this partial independence of
      upstream activators.

PMID- 8544827
TI  - Directed inactivation of the psbI gene does not affect photosystem II in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - PsbI is a small, integral membrane protein component of photosystem II (PSII), a
      pigment-protein complex in cyanobacteria, algae and higher plants. To understand
      the function of this protein, we have isolated the psbI gene from the unicellular
      cyanobacterium Synechocystis sp. PCC 6803 and determined its nucleotide sequence.
      Using an antibiotic-resistance cartridge to disrupt and replace the psbI gene, we
      have created mutants of Synechocystis 6803 that lack the PsbI protein. Analysis
      of these mutants revealed that absence of the PsbI protein results in a 25-30%
      loss of PSII activity. However, other PSII polypeptides are present in near wild
      type amounts, indicating that no significant destabilization of the PSII complex
      has occurred. These results contrast with recently reported data indicating that
      PsbI-deficient mutants of the eukaryotic alga Chlamydomonas reinhardtii are
      highly light-sensitive and have a significantly lower (80-90%) titer of the PSII
      complex. In Synechocystis 6803, PsbI-deficient cells appear to be slightly more
      photosensitive than wild-type cells, suggesting that this protein, while not
      essential for PSII biogenesis or function, plays a role in the optimization of
      PSII activity.

PMID- 8544828
TI  - Regulation of nif gene expression in Enterobacter agglomerans: nucleotide
      sequence of the nifLA operon and influence of temperature and ammonium on its
      transcription.
AB  - The nucleotide sequence of a plasmid-borne 3.9 kb XhoI-SmaI fragment comprising
      the 3'-region of the nifM gene, the nifL and nifA genes and the 5'-region of nifB
      gene of Enterobacter agglomerans was determined. The genes were identified by
      their homology to the corresponding nif genes of Klebsiella pneumoniae. A typical
      sigma 54-dependent promoter and a consensus NtrC-binding motif were identified
      upstream of nifL. The predicted amino acid sequence of NifL showed close
      similarities to NifL of K. pneumoniae and Azotobacter vinelandii. However, no
      histidine residue was found to correspond to histidine-304 of A. vinelandii NifL,
      which had been proposed to be required for the repressor activity of NifL. The
      NifA sequence with a putative DNA binding motif (Q(x3) A(x3) G(x5)I) and an ATP
      binding site in the C-terminal and central domains, respectively, resembles that
      of other known NifA proteins. The function of the nifL and nifA genes was
      demonstrated in vivo using a binary plasmid system by their ability to activate a
      nifH promoter-lacZ fusion at different temperatures and concentrations of NH4+.
      Maximal promoter activity occurred at 25 degrees C, and it appears that the
      sensitivity of NifA to elevated temperatures is independent of NifL. The
      expression of nifL inhibited promoter activity in the presence of NifA when the
      initial NH4+ concentration in the medium exceeded 4 mM.

PMID- 8544829
TI  - Skippy, a retrotransposon from the fungal plant pathogen Fusarium oxysporum.
AB  - A retrotransposon from the fungal plant pathogen Fusarium oxysporum f. sp.
      lycopersici has been isolated and characterized. The element, designated skippy
      (skp) is 7846 bp in length, flanked by identical long terminal repeats (LTR) of
      429 bp showing structural features characteristic of retroviral and
      retrotransposon LTRs. Target-site duplications of 5 bp were found. Two long
      overlapping open reading frames (ORF) were identified. The first ORF, 2562 bp in
      length, shows homology to retroviral gag genes. The second ORF, 3888 bp in
      length, has homology to the protease, reverse transcriptase. RNase H and
      integrase domains of retroelement pol genes in that order. Sequence comparisons
      and the order of the predicted proteins from skippy indicate that the element is
      closely related to the gypsy family of LTR-retrotransposons. The element is
      present in similar copy numbers in the two races investigated, although RFLP
      analysis showed differences in banding patterns. The number of LTR sequences
      present in the genome is higher than the number of copies of complete elements,
      indicating excision by homologous recombination between LTR sequences.

PMID- 8544830
TI  - Alterations in chlorophyll a/b binding proteins in Solanaceae cybrids.
AB  - In this study we have constructed a number of plants (cybrids), in which the
      nuclear genome of Nicotiana plumbaginifolia is combined with the plastome of
      Atropa belladonna, or the nuclear genome of N. tabacum with plastomes of Lycium
      barbarum, Scopolia carniolica, Physochlaine officinalis or Nolana paradoxa. Our
      biochemical and immunological analyses prove that in these cybrids the biogenesis
      of the chlorophyll a/b binding proteins (CAB) of the light harvesting complex II
      (LHCII) is altered. Besides normal sized CAB polypeptides of 27, 25.5 and 25 kDa,
      which become less abundant, the cybrids analyzed have additional polypeptides of
      26, 24.5 and 24 kDa. Direct protein micro-sequencing showed that at least two
      truncated 26 kDa CAB polypeptides in plant cells containing a nucleus of N.
      plumbaginifolia and plastids of A. belladonna are encoded by the type 1 Lhcb
      genes. These polypeptides are 11-12 amino acids shorter at the N-terminus than
      the expected size. Based on the available data we conclude that the biogenesis of
      the LHCII in vivo may depend on plastome-encoded factor(s). These results suggest
      that plastome-encoded factors that cause specific protein degradation and/or
      abnormal processing might determine compartmental genetic incompatibility in
      plants.

PMID- 8544831
TI  - Mode of action of the qcr9 and cat3 mutations in restoring the ability of
      Saccharomyces cerevisiae tps1 mutants to grow on glucose.
AB  - Mutations in the TPS1 gene, which encodes trehalose-6-P synthase, cause a glucose
      negative phenotype in Saccharomyces cerevisiae. Antimycin A or disruption of the
      QCR9 gene, which encodes one subunit of the cytochrome bc1 complex, restore the
      ability to grow in glucose-containing media. Under these conditions the cell
      excreted a large amount of glycerol, corresponding to about 20% of the glucose
      taken up. Suppression appears to be achieved by diversion of accumulated
      glycolytic intermediates to the production of glycerol, thereby providing NAD+
      and phosphate for the glyceraldehyde-3-P dehydrogenase reaction. Analysis of the
      mutation sci1-1, which also suppresses the glucose-negative phenotype of tps1
      mutants, showed that glucose transport was decreased in sci1-1 mutants. The gene
      SCI1 was cloned and its nucleotide sequence revealed it to be identical to
      CAT3/SNF4. The suppression mediated by sci1-1 is attributable to a decrease in
      glycolytic flux.

PMID- 8544832
TI  - Two mitochondrial alcohol dehydrogenase activities of Kluyveromyces lactis are
      differently expressed during respiration and fermentation.
AB  - The lactose-utilizing yeast Kluyveromyces lactis is an essentially aerobic
      organism in which both respiration and fermentation can coexist depending on the
      sugar concentration. Despite a low fermentative capacity as compared to
      Saccharomyces cerevisiae, four structural genes encoding alcohol dehydrogenase
      (ADH) activities are present in this yeast. Two of these activities, namely K1ADH
      III and K1ADH IV, are located within mitochondria and their presence is dependent
      on the carbon sources in the medium. In this paper we demonstrate by
      transcription and activity analysis that KlADH3 is expressed in the presence of
      low glucose concentrations and in the presence of respiratory carbon sources
      other than ethanol. Indeed ethanol acts as a strong repressor of this gene. On
      the other hand, KlADH4 is induced by the presence of ethanol and not by other
      respiratory carbon sources. We also demonstrate that the presence of KLADH III
      and KLADH IV in K. lactis cells is dependent on glucose concentration, glucose
      uptake and the amount of ethanol produced. As a consequence, these activities can
      be used as markers for the onset of respiratory and fermentative metabolism in
      this yeast.

PMID- 8544833
TI  - Molecular characterization of spontaneous mutations at the scarlet locus of
      Drosophila melanogaster.
AB  - Six spontaneous mutations of the scarlet (st) locus of Drosophila melanogaster
      have been studied at the molecular level. Two of the mutants (st1 and stsp) arose
      in laboratory populations, while the other four (stcob, stct89, stdct and stdv)
      were isolated from natural populations. In five of these there is a DNA insertion
      within the st region and in four cases the insertion has been identified as being
      a transposable element; these include the retrotransposons 412 and B104/roo, and
      also jockey a member of the LINE family. In the other case (stdct), the insertion
      appears to consist of partially duplicated st sequences. In two of the mutants
      (st1 and stdv) the same transposable element (412) has inserted in the same
      orientation at exactly the same site within the st gene. The transposable element
      insertions are found in intron and exon regions of the st gene and also in the
      putative upstream regulatory region; insertions located in introns or exons
      result in the production of truncated st transcripts. The results show that the
      same types of transposable elements that cause spontaneous mutation in laboratory
      stocks of D. melanogaster also cause mutation in the wild.

PMID- 8544835
TI  - Homolog-scanning mutagenesis of the parathyroid hormone (PTH) receptor reveals
      PTH-(1-34) binding determinants in the third extracellular loop.
AB  - To identify determinants in the rat PTH receptor critical for binding the agonist
      peptide, PTH-(1-34), we systematically replaced 12 segments (5-33 residues) of
      the receptor's extracellular surface with the corresponding segments of the
      homologous rat secretin receptor and screened the resulting mutants in COS-7
      cells for altered PTH-(1-34) binding properties. Surface expression of mutant
      receptors was assessed by the binding of monoclonal antibody 12CA5 to the epitope
      (HA)-tagged receptors. Of the nine well expressed and therefore informative
      receptor mutants, four bound radiolabeled PTH-(1-34) at levels that were
      proportional to the corresponding levels of surface expression, whereas five
      mutants bound [125I]PTH-(1-34) to levels that were lower than predicted from the
      cell surface expression levels. These five mutations occurred at the
      extracellular (EC) end of transmembrane domain 1, the carboxy-terminal portion of
      the first EC loop, the second EC loop, and the third EC loop. We selected for
      further fine structure analysis the third EC loop; two specific residues, Trp-437
      and Gln-440, were identified at which mutations caused 9- to 16-fold reductions
      in PTH-(1-34)-binding affinity. The same mutations had little or no effect on the
      binding affinity of PTH-(3-34). This study provides new information on the
      location of PTH receptor regions important for high affinity agonist binding and
      identifies two residues in the third extracellular loop which may contribute to
      interactions involving the hormone's critical amino terminus.

PMID- 8544834
TI  - Cloning and characterization of brnQ, a gene encoding a low-affinity, branched
      chain amino acid carrier in Lactobacillus delbruckii subsp. lactis DSM7290.
AB  - A gene (brnQ), encoding a carrier for branched-chain amino acids in Lactobacillus
      delbruckii subsp. lactis DSM7290 was cloned in the low-copy-number vector pLG339
      by complementation of a transport-deficient Escherichia coli strain. The plasmid
      carrying the cloned gene restored growth of an E. coli strain mutated in 4
      different branched-chain amino acid transport genes at low concentrations of
      isoleucine, and increased its sensitivity to valine. Transport assays showed that
      leucine, isoleucine and valine are transported by this carrier and that transport
      is driven by the proton motive force. Nucleotide sequence analysis revealed an
      open reading frame of 1338 bp encoding a hydrophobic protein of 446 amino acids
      with a calculated molecular mass of 47864 Daltons. The start site of brnQ
      transcription was determined by primer extension analysis using mRNA from
      Lactobacillus delbruckii subsp. lactis DSM7290. The hydropathy profile suggests
      the existence of at least 12 hydrophobic domains that probably form membrane
      associated alpha-helices. Comparisons of the nucleotide sequence of brnQ from
      Lactobacillus delbruckii subsp. lactis DSM7290, the amino acid sequence of its
      product and the topology of the hydrophobic domains with those of the respective
      carrier genes and proteins of Salmonella typhimurium and Pseudomonas aeruginosa
      revealed extensive homology.

PMID- 8544836
TI  - Activation of cyclic nucleotide phosphodiesterases in FRTL-5 thyroid cells
      expressing a constitutively active Gs alpha.
AB  - The expression of a constitutively activated Gs alpha protein in the rat thyroid
      cell line FRTL-5 causes an increase in the hormone-independent adenylyl cyclase
      activity and promotes TSH-independent growth of the cells. In spite of the
      constitutive activation of the adenylyl cyclase, the basal cAMP levels in these
      cells are only marginally increased. To define the role of phosphodiesterases
      (PDEs) in the genesis of this phenotype, cyclic nucleotide hydrolysis was
      determined in two cell lines expressing a mutated Gs alpha (Q227L). In these
      cells, the hydrolysis of both cAMP and cGMP was markedly increased in comparison
      with normal cells. This increase is the result of the activation of different
      forms of PDEs. Analysis of the cGMP hydrolysis and Ca++/calmodulin stimulation of
      the PDE activity indicated that the activity of a Ca++/calmodulin-stimulated PDE
      is increased in both cell lines. In addition, an increase in high-affinity,
      rolipram-sensitive cAMP-PDE activity was associated in both cell lines with the
      appearance of a 67-68 kilodalton (kDa) protein that cross-reacts with two
      antibodies against cAMP-PDEs. This form had the properties of ratPDE3.2/PDE4D2, a
      cAMP-PDE that is inducible by TSH in wild type cells. That an increase in cAMP
      specific, rolipram-sensitive PDE plays a role in the phenotype induced by Q227L
      Gs alpha was confirmed by measurements of the mitogenic activity. Incubation with
      rolipram, which had no effect on wild type cells, caused an increase in cAMP
      levels and further stimulated TSH-independent proliferation in both cell lines
      carrying the mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544837
TI  - Importance of the most proximal GC box for activity of the promoter of human
      thyroid hormone receptor beta 1.
AB  - We wish to localize the sequences required for transcriptional expression of the
      thyroid hormone receptor beta 1 (TR beta 1). Constitutive activity of the
      promoter of human thyroid hormone receptor beta 1 was assessed by transient
      transfection of deletion constructs attached to luciferase as reporter, into P19,
      GH3, HepG2, H19-7, and COS1 cells. A 40-base pair fragment of the beta 1 promoter
      including the TATA box induced minimal luciferase activity, which was considered
      basal activity. The activities of various lengths of the beta 1 promoter were
      estimated relative to the minimal promoter in five cell lines. The region between
      -130 and -40 was crucial for constitutive activity in all cell lines. Further
      deletion analysis in HepG2 cells showed that two regions mainly augmented the
      transcriptional activity of the minimal 40 base pair fragment. One region located
      at -115 to -93, which is highly GC-rich, included the most proximal of five
      putative GC boxes present in the whole 1325-base pair promoter. A second region
      contributing to expression of TR beta 1 in HepG2 cells is at -70 to -40. Mutation
      of the most proximal GC box strongly suppressed transactivity of the whole
      promoter in P19 and HepG2 cells. In contrast, mutations in the other GC boxes did
      not suppress transactivation in P19 cells and slightly suppress activation in
      HepG2 cells. In Schneider cells, which do not express Sp1, transactivity of the
      region distal to -40 is positively regulated by cotransfection with a vector
      expressing Sp1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544838
TI  - A motif in PSG11s mediates binding to a receptor on the surface of the
      promonocyte cell line THP-1.
AB  - The pregnancy-specific glycoproteins (PSG) form a large family of essential
      pregnancy proteins, but their biological function is unknown. We have
      investigated whether one function of the PSG is to interact with cells of the
      maternal immune system. Normal human peripheral blood mononuclear cells,
      activated with phorbol ester, are shown to bind to purified placental PSG. This
      binding activity can be mimicked using a chemically synthesized peptide ligand
      containing the Arg-Gly-Asp (RGD) motif present in the N-terminal domain of
      PSG11s. The PSG11s receptors are present on cells of the myeloid cell lineage but
      not of the T cell or B cell lineages. The binding is mediated in part by the RGD
      motif and can be competed against by appropriate RGD-containing, but not Arg-Ala
      Asp (RAD)-containing, ligands. Ligand binding requires a functional cytoskeleton.
      By examining the U937 and THP-1 promonocyte cell lines, the presence of receptors
      with two different binding characteristics are demonstrated. The THP-1 receptor
      is identified by chemical cross-linking as a protein of 46 kilodaltons (kDa), and
      affinity chromatography demonstrates the presence of three protein species of 32
      kDa, 16.8 kDa, and 15.9 kDa, suggesting the receptor has multiple subunits.

PMID- 8544839
TI  - The proglucagon gene upstream enhancer contains positive and negative domains
      important for tissue-specific proglucagon gene transcription.
AB  - The gene encoding proglucagon is restricted in expression to the central nervous
      system, endocrine pancreas, and intestine. Transgenic experiments indicate that
      the proglucagon gene upstream enhancer (GUE) element is a principal determinant
      of both the tissue specificity and the relative level of proglucagon gene
      transcription. We have now sequenced the rat proglucagon GUE and analyzed the
      transcriptional properties of proglucagon-luciferase fusion genes (that contain
      5'- and 3'-deletions in the GUE) after transfection of islet (InR1-G9) and
      enteroendocrine (STC-1 and GLUTag) cell lines. The GUE contains both positive and
      negative elements that are recognized differentially in islet vs. intestinal cell
      lines. The transcriptional properties of the GUE sequences were more similar in
      cell lines of intestinal (STC-1 and GLUTag) compared with islet (InR1-G9)
      phenotypes. The electrophoretic mobility shift assay was used to identify
      specific domains of the GUE that interacted with nuclear proteins from islet and
      intestinal cells. Several GUE sequences recognized proteins present in both
      fibroblast and endocrine cell lines. In contrast, electrophoretic mobility shift
      assay experiments also identified 1) GUE-protein complexes common to both islet
      and intestinal cell lines and 2) GUE-protein complexes specific to either islet
      or intestinal lineages. One of the GUE subdomains, designated GLUE1, displayed
      enhancer-like activity in InR1-G9 and GLUTag, but not BHK, cell lines. Taken
      together, these observations demonstrate that the proglucagon GUE is comprised of
      multiple positive and negative domains that likely function in a combinatorial
      fashion to regulate islet and intestinal-specific proglucagon gene transcription.

PMID- 8544840
TI  - Functional interaction of ligands and receptors of the hematopoietic superfamily
      in yeast.
AB  - Circulating peptide hormones and growth factors interact with cell surface
      receptors to initiate specific cellular responses. These complexes can consist of
      a simple association between two proteins or a more elaborate association of
      multiple proteins. We describe the functional expression of ligands and
      corresponding receptors in a microbial system useful for the rapid dissection of
      these important protein interactions. GH or PRL and extracellular domains of
      their respective receptors were functionally expressed as fusion proteins in an
      extended two-hybrid protein-protein interaction system. Reversible and specific
      ligand-receptor interactions were demonstrated by concurrent expression of free
      ligand peptides (GH or PRL) as binding competitors. The versatility established
      by expressing three heterologous proteins allowed for the investigation of higher
      order structures. Ligand-dependent GH receptor dimerization was demonstrated but
      PRL receptor dimerization was not observed in an analogous assay, suggesting that
      these related growth factors may not engage receptors in a similar manner.
      Additionally, significant association of GH receptors was observed in the absence
      of ligand, suggesting that there may be substantial avidity between these
      receptor proteins before ligand binding. Ligand-dependent and ligand-independent
      receptor dimerization was demonstrated by vascular endothelial growth factor and
      receptor proteins in similar assays. These findings indicate that extracellular
      protein interactions such as ligand-receptor association, as well as the
      formation of higher order protein structures important for the activation of
      hematopoietic receptors, can be rapidly investigated in this microbial expression
      system.

PMID- 8544841
TI  - Difference in transcriptional activity of two homologous CYP21A genes.
AB  - Steroid 21-hydroxylase (CYP21) deficiency is the major cause of congenital
      adrenal hyperplasia, a common genetic disease due to steroid imbalance. The main
      cause for the mutation of the CYP21A2 (c21B) gene is conversion of its nucleotide
      sequence to the neighboring homologous but nonfunctional c21A gene. In this
      report the transcriptional activities of the c21A and c21B genes have been
      analyzed. Transient transfection assays showed that transcription derived from
      the c21A gene was about 5-fold lower in strength than that of the c21B gene,
      although both sequences responded to cAMP normally in two adrenocortical cell
      lines. The normal response to cAMP could probably be attributed to equal
      activation of both genes by a transcription factor Nur77. The lower
      transcriptional activity of the c21A gene was attributed to sequence changes
      within 167 base pairs of the 5'-flanking region, which differs from the c21B gene
      by only four nucleotides at positions around -100. These four nucleotide changes
      render the c21A sequence to bind proteins less tightly than the -100 region of
      the c21B sequence, which binds proteins such as transcription factor Sp1 in
      electrophoretic mobility shift assays. The reduced transcription due to
      nucleotide changes at the regulatory region of the c21A gene, in combination with
      other mutations in the coding region, could play important roles in 21
      hydroxylase deficiency.

PMID- 8544842
TI  - Synergistic effects of inhibins and mullerian-inhibiting substance on testicular
      tumorigenesis.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily regulate
      diverse physiological processes in multiple tissues. In particular, important
      roles for the inhibins and mullerian-inhibiting substance (MIS) have been
      demonstrated in the regulation of cell growth control both in vitro and in vivo.
      Inhibin-deficient male and female mice develop mixed granulosa/Sertoli cell
      tumors with nearly 100% penetrance. MIS-deficient male mice develop as
      pseudohermaphrodites with oviducts and uteri. In addition, MIS-deficient males
      have Leydig cell hyperplasia and, in one case, a Leydig cell tumor. To determine
      whether MIS could modify the development of the granulosa/Sertoli cell tumors in
      inhibin-deficient mice or whether inhibin could alter the development of the
      Leydig cell hyperplasia of MIS-deficient mice, animals deficient for both
      inhibins and MIS were generated. Adult inhibin/MIS-deficient male mice developed
      testicular tumors and large fluid-filled uteri. The accumulation of uterine fluid
      was due in part to an increase in estradiol secretion from the tumors and was
      blocked by a pure estrogen antagonist, ICI 182,780. The testes of the inhibin/MIS
      deficient males developed granulosa/Sertoli cell tumors and Leydig cell neoplasia
      earlier, grew faster, were less hemorrhagic, and produced less estradiol than the
      testes of inhibin-deficient controls. These results demonstrate that inhibin and
      MIS synergize to influence testicular tumor development.

PMID- 8544843
TI  - Hormonal and developmental regulation of the steroidogenic acute regulatory
      protein.
AB  - A crucial event in the acute regulation of steroidogenesis by trophic hormones is
      the delivery of cholesterol into the mitochondria where it is converted to
      pregnenolone by the cholesterol side chain cleavage enzyme. Although considerable
      controversy exists regarding the exact mechanisms that underlie this acute
      response to hormone stimulation, recent studies suggest that the Steroidogenic
      Acute Regulatory (StAR) protein, a hormone-induced 30-kilodalton mitochondrial
      protein, plays an essential role. We now extend these studies by establishing in
      MA-10 mouse Leydig tumor cells a temporal relationship between levels of StAR
      expression and steroidogenesis in response to hormone stimulation. These data
      indicate that trophic hormones regulate StAR mRNA and protein within a time frame
      concomitant with the acute production of steroid hormones and provide the first
      evidence implicating changes in StAR transcription and/or mRNA stability in the
      functional response of steroidogenic cells to hormone action. In addition, in
      situ hybridization analyses of StAR expression in embryonic and adult mice
      demonstrated a precise spatial and temporal relationship in vivo between StAR
      expression and the capacity to produce steroid hormones. These experiments
      strengthen considerably the evidence that StAR is the key mediator of the acute
      induction of steroidogenesis and provide new insights into the mechanisms by
      which trophic hormones activate steroidogenesis in steroidogenic cells.

PMID- 8544844
TI  - Wilms' tumor protein WT1 as an ovarian transcription factor: decreases in
      expression during follicle development and repression of inhibin-alpha gene
      promoter.
AB  - WT1, a gene deleted in some Wilms' tumors, encodes a transcription factor with
      zinc fingers and shares homology with proteins in the early growth response gene
      family. Although defects in the WT1 gene are associated with nephroblastoma and
      genitourinary malformation, the specific function of WT1 in the gonads remains
      unclear. We investigated the expression of WT1 transcripts in rat ovary during
      follicle development by Northern blotting, RNase protection assay, and in situ
      hybridization. Abundant WT1 transcripts were found in the ovary, testis, uterus,
      and kidney, with lower levels in the heart and pancreas. Treatment with estrogen
      or gonadotropins did not affect the concentration of ovarian WT1 mRNA. In situ
      hybridization analysis indicated that ovarian WT1 mRNA is expressed exclusively
      in the surface epithelium and granulosa cells of primordial, primary, and
      secondary follicles, and its levels decrease during follicle growth. Although
      RNase protection assay suggested the presence of four alternatively spliced forms
      of WT1 mRNA, the ratio of these transcripts remains constant during ovarian
      growth. Developmental changes in the expression of two granulosa cell
      differentiation marker genes, inhibin-alpha and FSH receptor, were found to be
      inversely correlated with WT1 levels. Because potential WT1-binding sites were
      found in the promoter of inhibin-alpha gene, we further tested whether WT1 might
      regulate the expression of this gene. Cotransfection of a WT1 expression vector
      with a promoter reporter plasmid of inhibin-alpha resulted in the repression of
      promoter activities in CHO cells in a dose-dependent manner. These results
      suggest that WT1 is expressed in high levels in granulosa cells of primordial,
      primary, and secondary follicles but decreases with follicle development. This
      transcription factor might be a repressor of ovarian differentiation genes in the
      granulosa cells and play a role in arresting the differentiation of immature
      follicles.

PMID- 8544845
TI  - Characterization and regulation of the mouse insulin receptor substrate gene
      promoter.
AB  - To evaluate the potential for regulation of the insulin receptor substrate IRS-1,
      we have cloned the mouse IRS-1 gene, identified its promoter, and analyzed
      promoter activity in the basal state and in response to stimulation. The 5'
      region of the mouse IRS-1 gene lacks typical CAAT and TATA boxes but contains
      nine potential Sp1 binding sites consistent with a housekeeping gene. The 5'
      region of the IRS-1 gene also has significant regions of homology with the
      promoters of the progesterone receptor gene, the insulin-like growth factor I
      receptor gene, and the androgen receptor gene. Multiple transcription start sites
      were identified 0.4-1.2 kilobases (kb) upstream from the start codon. Using a
      chloramphenicol acetyl transferase assay in Chinese hamster ovary (CHO) cells,
      basal promoter activity was present in the 3.2 kb 5'-flanking region of IRS-1
      gene. Within this region, there were 184-base pair and 60-base pair negative
      regulatory elements at -3.2 kb and -1.6 kb surrounded by positive elements. By
      gel shift assay, a nuclear factor was identified in CHO cells which binds to 
      1606 and -1586 sequence in the negative regulatory element and appears to be
      distinct from C/EBP, CREB, and AP-1. In 3T3-F442A adipocytes dexamethasone
      treatment significantly decreased IRS-1 mRNA and IRS-1 protein. This was due to a
      decrease in the half-life of IRS-1 mRNA, with no change in IRS-1 promoter
      chloramphenicol acetyl transferase activity. Insulin also decreased IRS-1 protein
      by approximately 60% within 9 h but did so without altering IRS-1 mRNA levels or
      chloramphenicol acetyl transferase activity. Thus, both insulin and dexamethasone
      down-regulate IRS-1 expression at the posttranscriptional level; with insulin
      this is probably due to an effect on protein half-life, whereas with
      dexamethasone the effect is due to a change in the half-life of IRS-1 mRNA.

PMID- 8544846
TI  - Alternative leader sequences in insulin-like growth factor I mRNAs modulate
      translational efficiency and encode multiple signal peptides.
AB  - Rat insulin-like growth factor I (IGF-I) mRNAs contain multiple 5'-untranslated
      regions due to the use of leader exons transcribed from several transcription
      initiation sites and to alternative splicing within leader exon 1. Synthetic RNAs
      with 5'-ends corresponding to the use of exon 1 transcription initiation sites
      were translated in vitro into prepro-IGF-I peptides initiated at a Met-48 codon
      in exon 1 or a Met-22 codon in exon 3, and RNAs with a 5'-end corresponding to
      the major exon 2 transcription start site were translated into a prepro-IGF-I
      peptide initiated at a Met-32 codon in exon 2. All forms of prepro-IGF-I were
      processed by canine pancreatic microsomes, suggesting that all these prepeptides
      function as signal peptides. The translational efficiency of IGF-I RNAs was
      inversely proportional to the length of the 5'-untranslated region. Mutation of
      the first of three upstream AUG codons in exon 1, which potentially initiates a
      14-amino acid open reading frame, did not affect prepro-IGF-I translation. The
      other two AUG codons are immediately followed by stop codons. The absence of both
      upstream AUG codons in a completely spliced exon 1-derived RNA enhanced the in
      vitro and in vivo translatability of this RNA as compared with the full-length
      RNA. Mutation of the downstream initiation codon in particular increased
      translational efficiency in vitro and in intact cells, suggesting that an
      inefficient reinitiation event at the Met-48 codon contributes to the poorer
      translation of IGF-I mRNAs in which these upstream AUGUGA motifs occur. We
      conclude that IGF-I mRNAs potentially encode multiple forms of preproIGF and that
      specific differences in their 5'-untranslated regions provide a molecular basis
      for translational control of IGF-I biosynthesis.

PMID- 8544847
TI  - Impaired glucose tolerance and increased weight gain in transgenic rats
      overexpressing a non-insulin-responsive phosphoenolpyruvate carboxykinase gene.
AB  - The effects of an overexpressed, non-insulin-responsive gluconeogenic enzyme,
      phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32), on glucose
      homeostasis were investigated. Transgenic rats harboring a metallothionein-driven
      PEPCK gene (lacking the entire PEPCK upstream-regulatory region) expressed
      transgene PEPCK mRNA in the key gluconeogenic tissues, liver and kidney. Female
      transgenic rats, studied at 10 weeks of age, showed mild fasting hyperglycemia
      (6.9 +/- 0.2 vs. 5.9 +/- 0.1 mM P = 0.002 n = 6), hyperinsulinemia (92.2 +/- 4.0
      vs. 54.0 +/- 6.6 pM, P = 0.001, n = 6), impaired glucose tolerance and increased
      weight gain (178.3 +/- 3.2 vs. 153.4 +/- 2.5 g, P = 0.001, n = 16 and n = 13
      transgenic and control rats, respectively). Despite hyperinsulinemia at this age,
      kidneys of transgenic rats maintained a significant 20% elevation of total PEPCK
      enzyme activity, while total liver PEPCK activity was not reduced. This study
      suggests that an insulin-resistant step in the gluconeogenic pathway can lead to
      glucose intolerance and an increase in weight. These rats offer the unique
      opportunity to study the metabolic consequences of chronic, mild excess glucose
      supply, as seen in non-insulin-dependent diabetes.

PMID- 8544848
TI  - Activation of human insulin-like growth factor binding protein-1 gene promoter by
      a distal regulatory sequence in a human endometrial adenocarcinoma cell line.
AB  - Insulin-like growth factor-binding protein-1 (IG-FBP-1) is the major secretory
      protein of decidualized human endometrium. To understand IGFBP-1 gene regulation
      in human endometrium, we studied the IGFBP-1 gene promoter activity in human
      endometrial adenocarcinoma cell line HEC-1B. Previously, we have reported that a
      105-base pair (bp) ClaI/RsaI fragment, from -2732 to -2628, of IGFBP-1 promoter
      enhances promoter activity by 10-fold in HEC-1B cells. In this study we have
      characterized the activation of IGFBP-1 promoter by this distal regulatory
      sequence. Transient transfection assays with deletion constructs demonstrated
      that the activating cis-elements were located in a 59-bp fragment, from -2686 to 
      2628, which enhanced promoter activity 50-fold. Transient transfections and gel
      mobility shift assays with oligo-directed mutants revealed three cis-elements
      within this 59-bp region: I) ATGGGTGGGA (-2675 to -2666), II)
      GCTGAGCAAGTGCACAACTATCC (-2660 to -2638), and III) AGGGCGGAGT (-2637 to -2628).
      In nuclear extracts of HEC-1B cells, at least two proteins bound to cis-element
      III, one of which was transcription factor Sp1 since antibody against Sp1 caused
      a supershift in a gel mobility shift assay. A protein with a molecular mass of
      approximately 100 kilodaltons bound to cis-element I as revealed by Southwestern
      blotting. An unidentified protein bound to cis-element II. Mutations in cis
      element I, II, and III reduced promoter activity by 37%, 86%, and 88%,
      respectively, indicating that there was a synergistic function among these three
      cis-elements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544849
TI  - Pancreatic-specific expression of the glucose transporter type 2 gene:
      identification of cis-elements and islet-specific trans-acting factors.
AB  - A defect in glucose sensing of the pancreatic beta-cells has been observed in
      several animal models of type II diabetes and has been correlated with a reduced
      gene expression of the glucose transporter type 2 (Glut2). In a transgenic mouse
      model, expression of Glut2 antisense RNA in pancreatic beta-cells has recently
      been shown to be associated with an impaired glucose-induced insulin secretion
      and the development of diabetes. To identify factors that may be involved in the
      specific decrease of Glut2 in the beta-cells of the diabetic animal, an attempt
      was made to localize the cis-elements and trans-acting factors involved in the
      control of Glut2 expression in the endocrine pancreas. It was demonstrated by
      transient transfection studies that only 338 base pairs (bp) of the murine Glut2
      proximal promoter are needed for reporter gene expression in pancreatic islet
      derived cell lines, whereas no activity was detected in nonpancreatic cells.
      Three cis-elements, GTI, GTII, and GTIII, have been identified by DNAse I
      footprinting and gel retardation experiments within these 338 bp. GTI and GTIII
      bind distinct but ubiquitously expressed trans-acting factors. On the other hand,
      nuclear proteins specifically expressed in pancreatic cell lines interact with
      GTII, and their relative abundance correlates with endogenous Glut2 expression.
      These GTII-binding factors correspond to nuclear proteins of 180 and 90
      kilodaltons as defined by Southwestern analysis. The 180-kilodalton factor is
      present in pancreatic beta-cell lines but not in an alpha-cell line. Mutation of
      the GTI or GTIII cis-elements decreases transcriptional activity directed by the
      338-bp promoter, whereas mutation of GTII increases gene transcription. Thus
      negative and positive regulatory sequences are identified within the proximal 338
      bp of the GLUT2 promoter and may participate in the islet-specific expression of
      the gene by binding beta-cell specific trans-acting factors.

PMID- 8544850
TI  - Selective loss of H-2Ds antigen on a murine B lymphoma due to a post
      transcriptional block in expression.
AB  - The major histocompatibility (MHC) class I antigens are coordinately expressed in
      most cells. However, some tumors or virus-infected cells lack expression of one
      MHC class I antigen, while expression of the other MHC class I antigens is
      unaffected. We previously described the selective expression of MHC class I
      antigens on a B-cell lymphoma from SJL/J mice called RCS5. This tumor expresses H
      2Ks, but has lost cell surface expression of H-2Ds. To understand the mechanism
      responsible for the selective loss of H-2Ds on the cell surface, we analysed H
      2Ds mRNA and protein in the RCS5 tumor. Here we report that H-2Ds mRNA was
      expressed in RCS5, but H-2Ds protein was not detected in cell lysates. To
      determine whether the H-2Ds mRNA from RCS5 was able to direct the synthesis of H
      2Ds protein, we performed cDNA cloning, in vitro translation and gene transfer
      experiments using a cell line related to RCS5 (cRCS-X). Our results indicated
      that the inhibition of H-2Ds expression in cRCS-X occurred after transcription of
      a non-defective H-2Ds mRNA. Furthermore, H-2Ds antigen expression was restored in
      cRCS-X using a retroviral vector to express the recombinant H-2Ds cDNA. These
      results indicate that the inhibition of H-2Ds expression could be overcome either
      by out competing an inhibitor that functions in trans or by removing cis-acting
      regulatory sequences from the endogenous H-2Ds mRNA.

PMID- 8544851
TI  - Analysis of the IgE-epitope of Der f 2, a major mite allergen, by in vitro
      mutagenesis.
AB  - Der f 2 is a major mite allergen composed of 129 amino acid residues. To
      determine the major epitopes on Der f 2 recognized by human IgE antibodies,
      artificial mutations were introduced to Der f 2 protein. The IgE-binding activity
      of Der f 2 was significantly decreased by deletion of 10 amino acids at the N
      terminus or nine amino acids at the C-terminus. Site-directed mutagenesis with a
      single amino acid replacement by Ala or Leu in both N- and C-terminal regions as
      well as a central portion was performed to generate 42 single-site mutations.
      Amino acid replacement around a disulfide bond of Cys8-Cys119 caused a marked
      decrease in IgE-binding activity. Furthermore, a distinct decrease in IgE-binding
      was also caused by Ala-substitution close to a disulfide bond of Cys73-Cys78 and
      by mutations of a few charged residues. From these results, it was concluded that
      the two disulfide-forming regions of Der f 2 and several charged residues are
      important for forming major epitope structures recognized by human IgE
      antibodies.

PMID- 8544852
TI  - A synthetic peptide-based polyoxime vaccine construct of high purity and
      activity.
AB  - An artificial protein containing four copies of a peptide comprising the C
      terminal 23 residues of influenza virus hemagglutinin was constructed using oxime
      chemistry and compared with two tetrameric multiple antigenic peptide (MAP)
      constructions of the same peptide displayed either radially or linearly which
      were made by conventional techniques. The tetra-oxime was much more homogeneous
      yielding a single peak on reversed phase HLPC and the correct mass spectrum. In
      addition, the tetra-oxime was found to be recognized by anti-peptide antibodies,
      to stimulate at low concentrations a T-cell clone and also to elicit in mice high
      titres of antibodies which were able to recognize native virus. The modular
      polyoxime approach, which permits artificial proteins to be assembled rapidly, in
      high yield and in high purity, is expected to lead to an increase in the use of
      artificial proteins in vaccine technology.

PMID- 8544853
TI  - Sera from HIV-1 infected individuals in all stages of disease preferentially
      recognize the V3 loop of the prototypic macrophage-tropic glycoprotein gp120 ADA.
AB  - The outer membrane glycoprotein gp120 and the transmembrane glycoprotein gp41 are
      predominant targets of the humoral immune response to infection by human
      immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the
      principal neutralizing domain and is the primary target of neutralizing
      antibodies directed against the envelope proteins of HIV-1. The V3 loop is also
      the major determinant for HIV-1 cell-specific tropism. To further characterize
      the humoral immune response directed against the gp120 envelope proteins, we
      expressed two prototypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric
      gp120 envelope proteins in stable transfected Drosophila melanogaster Schneider 2
      cells. Sera from four infected adults over the course of infection [McNearney et
      al. (1992) Proc. natn. Acad. Sci. U.S.A. 89, p. 10,242] were assayed for
      reactivity with the respective envelope proteins. Sera obtained at early stages
      preferentially recognized the gp120 envelope protein ADA, whereas in later stages
      of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and
      gp120 ADA. Chimeric envelope proteins revealed that the humoral response was
      directed primarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from
      HIV-1 infected individuals in different stages of the disease were tested.
      Reactivity of sera with the gp120 envelope protein ADA was seven-fold higher than
      with the gp120 envelope protein LAI/HXB2. Our results suggest that the humoral
      immune response is preferentially elicited against the V3 loop of the prototypic
      macrophage-tropic gp120 envelope protein ADA.

PMID- 8544854
TI  - Characterization of a monoclonal antibody directed against the NH2 terminal area
      of interleukin-2 (IL-2) and inhibiting specifically the binding of IL-2 to IL-2
      receptor beta chain (IL-2R beta).
AB  - An anti-human IL-2 mAb (19B11/beta) was found to selectively block the binding of
      IL-2 to TS1 beta cells expressing the interleukin-2 receptor beta (IL-2R beta)
      without affecting binding to TS1 alpha cells expressing the IL-2R alpha receptor.
      It also specifically inhibits the IL-2 driven cell proliferation in TS1 beta
      cells. These observations have lead to the hypothesis that its epitope is related
      to an IL-2 area involved in binding with IL-2R beta chain. This epitope was
      identified using various peptides covering the N-terminal half (including alpha
      helix A) of the 133 amino acids of IL-2. MAb 19B11/beta does not recognize
      peptides 30-54 and 44-54 but recognizes peptides 1-22 and 1-30 with a good
      affinity. Furthermore, threonine in position no. 3 was found to be critical for
      the binding of mAb 19B11/beta. A relationship between the epitope of mAb
      19B11/beta and the glycosylation of the IL-2 molecule was observed. This further
      demonstrates that the NH2 terminal area of IL-2 is critical for IL-2/IL-2R beta
      interactions. Two other mAbs were studied during the course of this work. They
      served as control for the study of mAb 19B11/beta and provide some additional
      insight concerning the question of IL-2/IL-2R structure-function. MAb 16F11/alpha
      selectively blocks the IL-2 binding to TS1 alpha cells. The epitope of mAb 16F11
      is conformational and it was not possible to study the corresponding IL-2/IL-2R
      alpha region of interaction. Epitope of mAb 3H9 is localized between residues 30
      and 54 and does not affect the binding of IL-2 to IL-2R alpha.

PMID- 8544855
TI  - Specificity of monoclonal antibodies produced against phosphorothioate and ribo
      modified DNAs.
AB  - A large number of phosphorothioate DNAs and mixed ribo/deoxyribo duplexes were
      prepared and their immunogenicity was studied in mice. Only those polymers which
      were nuclease-resistant were immunogenic and in these cases monoclonal antibodies
      were prepared. The specificity of the antibodies was measured by direct and
      competitive Solid Phase Radioimmune Assay (SPRIA) and on this basis four types of
      antibody could be identified. Type I antibodies are specific for the immunizing
      polymer and show very limited crossreactivity. For example, Jel 384 binds only to
      poly(dsA).poly(dT); Jel 453 and 462 bind only to poly(dsG).poly(dC) and
      poly(dsG).poly(dm5C). Type II antibodies bind to most polymers containing the
      appropriate modification but will not bind to unmodified DNAs. For example, Jel
      343 binds to most thio DNAs regardless of sequence; Jel 346 binds well to most
      ribose-containing polymers and may be a useful reagent for the detection of the
      'A' family of conformations. Type III antibodies bind to most nucleic acids
      whether modified or not. Their specificities are similar to autoimmune
      antibodies. Type IV antibodies are single strand-specific such as Jel 383 which
      binds to poly(dT). There were no examples of antibodies which bound specifically
      to the immunizing DNA and the unmodified polymer. Thus, modified DNAs cannot be
      used to prepare sequence-specific reagents. Also, the immunogenicity of modified
      nucleic acids may limit their usefulness in antisense technologies.

PMID- 8544856
TI  - Use of a novel mutagenesis strategy, optimized residue substitution, to decrease
      the off-rate of an anti-gp120 antibody.
AB  - We have developed a novel strategy to decrease the antibody:antigen off-rate
      which we call optimized residue substitution. This strategy employs alanine
      substitution to first identify residues non-optimal for binding, as evidenced by
      a decrease in off-rate upon alanine replacement. These positions are then
      individually randomized to all amino acids, and the best replacement for each
      position determined. Finally, a construct which combines all optimized
      substitutions is generated and evaluated. We applied this strategy to the heavy
      chain CDR3 of P5Q, a scFv antibody which recognizes an epitope on the V3 loop of
      HIV gp120. We identified two amino acid substitutions that together decrease the
      off-rate by nearly ten-fold. The contributions by the two substitutions were near
      additive, indicative of independent affects on binding. We suggest that this
      strategy can be generalized to strengthen protein:ligand and protein:protein
      interactions in other systems.

PMID- 8544857
TI  - Probing immunogenicity of a T cell epitope by L-alanine and D-amino acid
      scanning.
AB  - All residues of the I-Ed restricted fragment 24-36 of a snake toxin were
      individually changed into L-alanine and the corresponding D-enantiomer. Four
      analogs substituted with L-Ala at positions 25;30, 31 and 33, and nine analogs
      substituted with a D-residue along the stretch 25-33 lost most (position 28) or
      all their capacity to stimulate a toxin-specific T hybridoma. None of these
      analogs stimulated splenocytes from mice immunized with the peptide 24-36. Only
      the L-A31 and D-W29 modified analogs could prime a T cell response which,
      however, showed no cross-reactivity with the native peptide, demonstrating that T
      cell response selectivity can be deeply modified by mutation or configuration
      inversion of a single residue. Our data suggest that (i) the region 25-33 is the
      core of the T epitope that binds to I-Ed, and (ii) Y25 R30 and R33 contribute to
      the peptide binding by anchoring into pockets of I-Ed. In agreement with T cell
      priming observations, only the L-A31 and D-W29 modified analogs elicited strong
      antibody responses, just like the peptide 24-36, whereas nearly all other analogs
      were less immunogenic. All but the L-Ala30 and L-Ala33 modified analogs were
      recognized by a 24-36 specific antiserum as well as the native peptide.
      Altogether, our results show that substitution by D-amino acid in a peptide could
      be particularly well-suited for either minimizing the risk of hypersensitivity or
      designing peptidic vaccines.

PMID- 8544858
TI  - Characterization of the variable regions of a chimpanzee monoclonal antibody with
      potent neutralizing activity against HIV-1.
AB  - The variable (V) regions of C108G, a potent neutralizing chimpanzee mAb against a
      glycan-dependent epitope in the V2 region of HIV-1 gp120, have been characterized
      for reactivity with human VH and VK family-specific antisera, and their
      nucleotide sequences have been determined and analysed. To our knowledge, this is
      the first study characterizing expressed chimpanzee VH and VK genes. Results show
      that C108G expresses members of the VH3 and VK1 families, the largest VH and VK
      families in humans, respectively. Nucleotide and amino acid sequence analyses
      reveal that C108G VH is most homologous to the human VH3 germline gene, hsigdp33
      or V3-43, and the human JH4 minigene. The human germline VK1 gene that is most
      homologous to C108G VK, hsigk1012, was previously observed in unmutated form in a
      human autoantibody with anti-i red blood cell antigen specificity and in seven
      human Fabs and a mAb directed against epitopes overlapping the CD4-binding site
      of HIV-1 gp120. This germline gene was unmutated in three of the human Fabs and
      was somatically mutated in the other four Fabs and the mAb. In addition, the JK
      minigene was used in C108G VK, JK2, is apparently over-represented in anti-HIV-1
      mAbs/Fabs; this minigene was used in 61% of the anti-gp120 human Fabs recently
      described and in three other anti-CD4-binding site human mAbs derived by EBV
      transformation. While the significance of these findings is unclear, they may
      suggest a bias in VK/JK gene usage and/or network regulation involving an
      hsigk1012/JK2 idiotope(s) in the antibody response to HIV-1. Both the C108G VH
      and VK genes showed evidence of somatic mutation and antigen selection that
      apparently occurred in vivo during chronic exposure to HIV-1 and its antigens.
      Surprisingly, this somatic mutation was most profound in the CDR3 region of C108G
      VK; this region shared only 48% nucleotide homology with hsigk1012 contrasted
      with a homology of 94% over the remainder of these two V gene sequences. Perhaps
      the most significant finding of this study is that the expressed VH and VK genes
      of chimpanzee mAb C108G are no more divergent from their most homologous human
      germline genes than are the expressed V genes of several recently characterized
      human anti-HIV-1 mAbs/Fabs from their apparent human germline genes. This
      suggests that chimpanzee mAbs are no more likely to elicit deleterious anti
      immunoglobulin responses in humans than are human mAbs and emphasizes the
      potential for development of chimpanzee mAbs as immunotherapeutic agents.

PMID- 8544859
TI  - Primary structures of three Armenian hamster monoclonal antibodies specific for
      idiotopes and metatopes of the monoclonal anti-fluorescein antibody 4-4-20.
AB  - This paper reports the complete V gamma, V kappa, C gamma 1 and C kappa
      nucleotide and deduced amino acid sequences of two hamster monoclonal anti
      metatype antibodies, 3A5-1 and 4A6. These antibodies have been previously
      characterized in terms of their binding and molecular stabilization properties
      with liganded murine monoclonal and single-chain antibody 4-4-20 active sites.
      Also reported are the complete V kappa and C kappa nucleotide and deduced amino
      acid sequence of hamster monoclonal anti-idiotype antibody 1F4, which is specific
      for the unliganded 4-4-20 active site. Oligonucleotide primers based on the 5'
      ends of murine variable genes, along with primers specific for murine IgG C gamma
      1 and kappa constant region genes, have been used in cDNA and polymerase chain
      reactions (PCRs) to amplify IgG cDNA from Armenian hamster/mouse hybridomas. The
      hamster C gamma 1 and C kappa domain sequences are highly homologous to
      previously reported murine sequences. The anti-idiotype mAb V kappa gene
      demonstrated strong similarity to the murine V kappa V gene subgroup while the
      two anti-metatype mAb V kappa genes approximated more closely to the murine V
      kappa III gene subgroup. The two anti-metatype mAbs utilized highly homologous V
      gamma genes, with differing HCDR 3 regions, that appeared similar to the murine V
      gamma I(a) subgroup. These sequence determinations represent the first primary
      structures reported for antibodies with anti-metatype activity and are additions
      to the relatively sparse hamster immunoglobulin genetic database. Results are
      discussed in terms of 4-4-20 active site specificity and anti-metatype activity,
      as well as immunoglobulin structural diversity in an anti-Ig immune response.

PMID- 8544860
TI  - The human antibody repertoire: heavy and light chain variable region gene usage
      in six alloantibodies specific for human HLA class I and class II alloantigens.
AB  - Peripheral blood B lymphocytes have been isolated from healthy individuals who
      were immunized with lymphocytes from HLA-incompatible donors and transformed with
      Epstein-Barr virus to produce human monoclonal cell lines specific for human HLA
      molecules. The cell lines have been previously characterized and are known to
      bind to various class I and class II alloantigens. In this report we describe the
      molecular characterization of the heavy and light chain variable region gene
      segments that are utilized by these monoclonal antibodies. Using the polymerase
      chain reaction and primer pairs specific for the respective constant region and
      VH or VL family, rearranged variable region gene segments were amplified from
      cDNA from individual cell lines. Products were then subcloned, sequenced and
      analysed for gene usage and apparent somatic mutation. The results show that the
      VH3 gene family predominates in a group of six heavy chains (four out of six)
      with one VH1 and one VH4 gene segment. The light chain variable region gene
      family usage is more diverse with 2 V kappa 3, 1 V kappa 1, 2 V lambda 2 and 1 V
      lambda 3. The extent of apparent somatic mutation is minimal, relative to our
      previous observations in a group of high affinity human monoclonal antibodies
      specific for pathogenic organisms.

PMID- 8544861
TI  - N-glycanase treatment of F(ab')2 derived from asymmetric murine IgG3 mAb
      determines the acquisition of precipitating activity.
AB  - The aim of this study was to analyse four anti-DNP asymmetrically glycosylated
      monoclonal IgG3 antibodies (194/2, 194/5, 194/6 and 194/12) before and after
      carbohydrate manipulation. Microheterogeneity in the composition of the
      carbohydrate moiety involved in Fab' glycosylation was detected using lectins.
      Additional O-glycosidic carbohydrate chains were detected within the Fc region of
      two monoclonal antibodies. Fab' glycosylation produced a difference in the
      binding constants (Ka) in each paratope of two orders of magnitude, as determined
      by means of primary ligand-antibody interaction. The difference in binding
      affinity and the importance of Fc-Fc interaction was evidenced by a lack of BSA
      DNP precipitation by the F(ab')2 fragments. The oxidation of the antibodies with
      sodium periodate caused the disappearance of the low affinity binding site as
      determined by fluorescence quenching. Furthermore, the enzymatic removal of the
      carbohydrate with N-glycanase determined the acquisition of precipitating
      activity by the F(ab')2 fragments.

PMID- 8544862
TI  - Purification of immunologically active recombinant 21.5 kDa isoform of human
      myelin basic protein.
AB  - We have designed and expressed in bacteria a recombinant fetal form of human
      myelin basic protein (21.5 kDa isoform; rhMBP21.5), a candidate autoantigen in
      multiple sclerosis. An exon 2 insertion, carboxy-terminal histidine tag and
      preferred bacterial codons differentiate the MBP21.5 gene from that encoding the
      adult, brain-derived form of human MBP (18.5 kDa isoform; hMBP18.5). MBPs were
      expressed at high levels in E. coli and extracted from whole cells by
      simultaneous acid solubilization and mechanical disruption. A nearly two-fold
      increase in recombinant protein was detected in strains harboring MBP genes with
      bacterial preferred codons compared to genes containing human codons. The
      recombinant molecules were purified in two steps, first by reversed-phase
      chromatographic separation and then by metal affinity chromatography. Dimeric
      forms of recombinant MBP21.5 were detected under physiological conditions,
      however, substitution of a serine for the single cysteine at amino acid residue
      81 resulted in only monomer formation. All forms of recombinant MBPs induced
      proliferative responses of human T lymphocytes specific for epitopes in MBP18.5
      kDa. In contrast, human T cell lines that recognize an exon 2-encoded epitope of
      MBP responded to the 21.5 kDa isoform of MBP, but not the 18.5 kDa isoform.

PMID- 8544863
TI  - Structural analysis of affinity maturation: the three-dimensional structures of
      complexes of an anti-nitrophenol antibody.
AB  - Affinity maturation of the immune response to nitrophenol-containing antigens has
      been extensively investigated. Significant strides made during the past several
      years with the advent of PCR technology have provided a wealth of biochemical
      knowledge. Structural investigations of the phenomena have however been limited.
      We have determined the three-dimensional structure of the Fab fragment of
      88C6/12, an anti-4-hydroxy-3-nitrophenyl acetic acid antibody complexed with the
      immunizing hapten and with a heteroclitic iodinated hapten. The crystallographic
      structure of the complexes reveals that the binding is stabilized by a number of
      hydrogen bonds and extensive van der Waals interactions between the hapten and
      the antibody. In addition, the Fab binding pocket contains a region of positive
      electrostatic potential well suited for interaction with the predominant
      resonance form of the nitrophenyl ring system. The observed heteroclicity towards
      the iodinated hapten is not a direct result of iodine-protein interactions, but
      results from the enhanced stability in the iodinated ring of the resonance form
      that binds the antibody. In addition this investigation provides a rationale for
      the strong preference for the substitution in the heavy chain from the germ-line
      gene encoded Trp 33 to Leu 33 in the mature anti-nitrophenol response.

PMID- 8544864
TI  - Molecular cloning and characterization of human thyroid peroxidase autoantibodies
      of lambda light chain type.
AB  - IgG class thyroid peroxidase (TPO) autoantibodies with kappa light (L) chains
      predominate in serum and the genes for a large repertoire of such autoantibodies
      have been characterized. The present study was performed to clone and
      characterize TPO autoantibodies with lambda L chains which comprise approximately
      20% of serum TPO autoantibodies. From a combinatorial IgG H/lambda L chain cDNA
      library in the phage display vector pComb3, 24 TPO-binding clones with lambda L
      chains were isolated, comprising three different heavy (H) and light (L) chain
      combinations. These combinations utilized two genes from the Vlambda II and IIIb
      families (closest germline genes DPL11 and hsigg11150) and three genes from the
      VH1, VH3 and VH4 families (VH26, 4.34 and hv1L1). The deduced amino acid
      sequences of these H chains were quite different from those of kappa F(ab)
      isolated using the same H chain library. We expressed the proteins for these
      three lambda F(ab), as well as for a lambda F(ab) (Humlv318 L chain/DP10-like H
      chain) previously isolated from another patient. The affinities for TPO of the
      lambda F(ab) (Kd 8 x 10(-10) M to 10(-7) M) were lower than those of the kappa
      F(ab) (Kd approximately 10(-10) M). For two lambda F(ab), both H and L chain
      genes were close to germline configuration, but there was no straightforward
      relationship between the extent of somatic mutation from germline configuration
      and affinity for TPO. All four lambda F(ab) bound less well to denatured TPO as
      to native TPO. The three F(ab) for which sufficient protein could be expressed
      for competition studies all recognized domain B within the immunodominant region
      on TPO previously identified using F(ab) with kappa L chains. Aside from these
      TPO-specific F(ab), only a few other human IgG class, organ-specific
      autoantibodies with lambda L chains have been characterized at the molecular
      level. Our study significantly augments the small database on this category of
      autoantibodies in general.

PMID- 8544865
TI  - Carbohydrate-induced modulation of cell membrane--III. Interaction of sialic acid
      and mannose with hamster splenic lymphocytes: a spin label study.
AB  - The role of different carbohydrates as ligands for adhesion molecules has been
      extensively studied. However, the physiological changes in the splenic
      lymphocytes on binding these ligands have never been studied. In this paper, we
      report that binding of sialic acid or mannose to hamster splenic lymphocytes
      restricts the mobility of membrane proteins and lipids as studied by EPR
      spectroscopy using spin probes. Binding of mucin and heparin totally restricts
      the mobility probably due to crosslinking of the surface lectins. Binding of
      these ligands also results in an increase in the viscosity of the cytoplasm.

PMID- 8544866
TI  - Genotoxicity assay of chloral hydrate and chloropicrine.
AB  - The chlorination by-products chloral hydrate and chloropicrine were assayed for
      genotoxicity in three short-term tests. Chloropicrine was 100-fold more potent
      than chloral in inducing mutations in strain TA100 of S. typhimurium (fluctuation
      test) and, at variance with chloral, was positive in the SOS chromotest using
      strain PQ37 of E. coli. On the other hand, only chloral caused a significant
      increase in the frequency of micronucleated erythrocytes following in vivo
      exposure of the amphibian Pleurodeles waltl newt larvae.

PMID- 8544867
TI  - Advantages and limitations of using fluorescence in situ hybridization for the
      detection of aneuploidy in interphase human cells.
AB  - Fluorescence in situ hybridization with chromosome-specific DNA probes is being
      increasingly utilized for the detection of chromosome aberrations induced in
      vitro and in vivo by chemical and physical agents. Although potentially a
      powerful technique, FISH studies for aneuploidy can be heavily influenced by
      cellular phenomena and hybridization artifacts which make the performance and
      interpretation of the results difficult. As a consequence, frequently
      hyperdiploid frequencies are reported in the literature which are substantially
      higher than one would expect based upon frequencies seen in conventional
      metaphase analyses. In this article, a number of the potential pitfalls that we
      have encountered while performing FISH analyses for aneuploidy are discussed and
      their potential impact on the observed hybridization frequencies is described.
      After considering these factors, the frequencies of lymphocyte nuclei containing
      3 and 4 chromosome copies are compared between metaphase values obtained from
      published human population studies and interphase values obtained from similar
      studies using FISH. It is concluded that by using caution in the evaluation of
      slides, interphase studies using FISH to detect hyperdiploidy and polyploidy can
      provide estimates of numerical alterations which closely reflect those seen
      during metaphase analysis using either FISH or conventional approaches. However,
      due to the inability of interphase analysis to distinguish hyperdiploidy from
      polyploidy as well as other potential problems, frequencies of aneuploid nuclei
      obtained using single label FISH should only be considered approximations of
      absolute frequencies. For additional accuracy, multi-color FISH with two or more
      different probes should be performed.

PMID- 8544869
TI  - DNA damaging and cell proliferative activity of 1-methyl-1-nitrosourea in rat
      glandular stomach mucosa.
AB  - The DNA damaging and cell proliferative activity of 1-methyl-1-nitrosourea (MNU),
      a glandular stomach carcinogen, was studied in the pyloric mucosa of male F344
      rats after administration by gastric tube. DNA damage was measured with
      unscheduled DNA synthesis (UDS) and DNA single strand scission as markers, while
      cell proliferation was measured with replicative DNA synthesis (RDS) and
      ornithine decarboxylase (ODC) as markers. MNU at doses of 30 and 60 mg/kg body wt
      and 80 min after administration dose-dependently induced UDS (49 and 79 (0 dose,
      19) dpm/micrograms DNA) measured by liquid scintillation counting in the presence
      of hydroxyurea (an inhibitor of RDS). RDS (DNA synthesis in the absence of
      hydroxyurea; 239 dpm/micrograms DNA at 0 dose) did not increase at that time. MNU
      at doses of 10 and 60 mg/kg body wt and 2 h after administration dose-dependently
      induced DNA single strand scission of 8.2 and 43.5 (0 dose, 1.4) elution rate
      constant (x 10(-3)/ml). MNU at doses of 30 and 60 mg/kg body wt and 24 h after
      administration dose-dependently induced an increase in RDS (1362 and 2393 (0
      dose, 682) dpm/micrograms DNA). MNU at doses of 60, 90 and 120 mg/kg body wt and
      24 h after administration dose-dependently induced an increase in ODC activity
      (22.0, 29.4 and 38.4 (0 dose, 6.3) p mol CO2/30 min/mg protein). These results
      suggest that MNU has possible tumor initiating activity (UDS and DNA single stand
      scission) and tumor promoting activity (RDS and ODC) in rat stomach mucosa.

PMID- 8544868
TI  - Synergistic action of N-nitrosodialkylamines and near-UV in the induction of
      chromosome aberrations in Chinese hamster lung fibroblasts in vitro.
AB  - N-Nitrosodialkylamines are promutagens and proclastogens, requiring metabolic
      activation for their actions. Previously, we showed that direct-acting bacterial
      mutagens can be formed from N-nitrosodialkylamines on exposure to near-UV. We
      have now found that N-nitrosodialkylamines with near-UV irradiation are
      clastogenic to Chinese hamster lung cells. When the cells in culture were
      irradiated with near-UV for 3 h in the presence of N-nitrosodimethylamine (NDMA),
      N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine
      (NPIP) or N-nitrosomorpholine (NMOR), and then further incubated for a total
      period of 24 h with the N-nitrosodialkylamines, chromosome aberrations were
      induced. Neither the N-nitrosodialkylamine nor near-UV alone were clastogenic.
      Severe clastogenicity (> 50% of cells examined showing aberrations) was observed
      for 0.5 mM NDEA, NPYR and NPIP. The order of the clastogenic activity was NDEA,
      NPYR > NPIP, NDMA > NMOR. This order differed from that of bacterial mutagenicity
      previously reported for these N-nitrosodialkylamines plus near-UV, in which NMOR
      gave the strongest activity. The chromosome aberrations induced by the NPYR and
      NDEA plus near-UV in CHL-cells were inhibited by superoxide dismutase,
      glutathione and L-cysteine. Dimethylsulfoxide or D-mannitol, scavengers of
      hydroxy radical, and L-histidine, a scavenger of single oxygen, were ineffective.
      These results suggest that superoxide formed by a synergistic action of an N
      nitrosodialkylamine and near-UV is the cause of the chromosome aberrations
      observed, an assumption consistent with the known ability of superoxide to cleave
      DNA.

PMID- 8544870
TI  - Effects of indomethacin and arachidonic acid on sister chromatid exchange
      induction by styrene and styrene-7,8-oxide.
AB  - Styrene is converted into styrene-7,8-oxide in human lymphocyte cultures, in a
      reaction probably mediated by oxyhemoglobin. As a consequence, styrene induces
      sister-chromatid exchanges (SCEs) in whole-blood lymphocyte cultures without
      exogenous metabolic activation systems. Another metabolic pathway that could be
      involved in the metabolism of styrene is cooxidation by prostaglandin
      endoperoxide synthase (PES). To study the role of PES in the metabolism of
      styrene, human whole-blood lymphocyte cultures were treated for the entire
      culture time of 72 h with styrene (0.5 and 1 mM) or styrene-7,8-oxide (50 and 100
      microM), in the presence and absence of 75 or 150 microM indomethacin (an
      inhibitor of PES) and arachidonic acid (substrate of PES). Indomethacin
      potentiated SCE induction by both styrene and styrene-7,8-oxide; a slight but
      statistically significant enhancement (16-32%; p < 0.05-0p < 0.001) was observed
      in all treatments with styrene and at 150 microM indomethacin in the case of
      styrene-7,8-oxide. At 150 microM, arachidonic acid induced a 15-20% suppression
      (p < 0.01) in SCE induction by both styrene (1 mM only) and styrene-7,8-oxide
      (100 microM only). Indomethacin or arachidonic acid did not alone influence the
      frequency of SCEs. The results suggest that PES acts as an inactivation route for
      styrene and styrene-7,8-oxide in human whole-blood lymphocyte cultures, possibly
      through PES-mediated binding to glutathione.

PMID- 8544871
TI  - PM2 DNA damage induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone
      (MX).
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a potent direct
      acting mutagen found in chlorinated drinking water. In the present study, the
      induction of DNA strand breaks and apurinic/apyrimidinic (AP) sites by MX in
      supercoiled PM2 DNA was examined using exonuclease III, which specifically
      cleaves the DNA at AP sites. The results showed that MX induced AP sites in great
      excess of direct strand breaks. In view of the known mutagenicity of AP sites,
      these results provide insight into the mechanism of MX-induced mutagenesis.

PMID- 8544872
TI  - Persistence of increased levels of ribosomal gene activity in CHO-K1 cells
      treated in vitro with demethylating agents.
AB  - The rate of ribosomal gene activity was evaluated by silver staining of the
      Nucleolus Organisers (NOs) in cultured CHO-K1 cells after a 12 h pulse with two
      demethylating agents (L-ethionine and 5-azacytidine). Silver staining of the NOs
      was measured every 24 h, from 24 up to 110 h after seeding. The purpose was to
      test the hypothesis that drug-induced demethylation is associated to heritable
      modifications of rDNA activity. Ribosomal gene activity was shown to be
      significantly increased by both agents. The increase persisted throughout the
      experiments, thereby suggesting the heritability of this epigenetic modification.
      The analysis of heritable DNA damage or modification is an important task in
      studying the risk of cancer onset and the mechanisms of cancer induction. In
      these studies two main results were obtained: (i) heritable DNA variations can be
      induced by both mutational and epigenetic changes; (ii) the modified end-point
      was not negatively selected.

PMID- 8544873
TI  - Mutagenic effects at hprt locus and in minisatellite sequences induced in V79
      cells by treatments with UV and methyl-nitro-nitroso guanidine.
AB  - DNA alterations induced in V79 cells treated with UV light or methyl-nitro
      nitrosoguanidine were analyzed by the mutagenicity test at the hprt locus and by
      DNA fingerprint analysis. Treated and control cells were seeded in the presence
      or absence of 6-thioguanine to determine mutant frequency and cell survival. From
      clonal cultures of the same cell populations we isolated a number of clones and
      grew them up individually to obtain appropriate amounts of DNA. High molecular
      weight DNA was digested with HinfI or HaeIII and hybridized with 32P-labelled
      33.15 multilocus probe. The induction of 6-thioguanine resistant cells depended
      on the mutagen dose. The highest value of mutant frequency obtained was 7475 x
      10(-6) (MNNG, 27 microM), corresponding to 0.7 percent of clonable cells. DNA
      fingerprint analysis carried on the same treated cells showed that DNA
      rearrangements occurred at minisatellites much more frequently than in
      transcribed sequences. UV irradiation produced the highest frequency of
      variation, modifying minisatellite patterns in about 50 percent of the analyzed
      clones.

PMID- 8544874
TI  - Enhanced reactivation of nitrous acid treated adenovirus is not associated with
      enhanced mutagenesis in pretreated with heavy metals HeLa cells.
AB  - The reversion frequency of an adenovirus 2 temperature-sensitive growth mutant
      treated with different doses of nitrous acid was determined after infection of
      control. UV-irradiated, cadmium chloride and zinc chloride treated HeLa cells. No
      enhanced mutagenesis was observed.

PMID- 8544875
TI  - Neural and Neuromuscular Aspects of Muscle Fatigue. Miami, Florida, November 10
      13, 1994. Abstracts.

PMID- 8544876
TI  - An evolutionary perspective on signaling in behavior and immunology.
AB  - Signaling and communication are important at different levels of biological
      organization. Signals exchanged between cells of the immune system initiate and
      coordinate the immune response; signals exchanged between individuals often
      coordinate social behavior. Behavioral ecologists interested in the evolution and
      functional design of signals exchanged between individuals have produced a theory
      of signaling and communication that stresses the importance of cooperation and
      conflict; if a conflict of interest between signaler and receiver is great
      enough, signals evolve towards greater reliability. We suggest that the
      application of signaling system theory to signals exchanged between cells within
      an individual will allow for a better understanding of immunity and intra
      individual communication in general, with potential for novel approaches to the
      treatment of disease.

PMID- 8544877
TI  - Tricky relatives: consecutive dichotomous speciation of gorilla, chimpanzee and
      hominids testified by immunological determinants.

PMID- 8544878
TI  - Time can be traded for intensity in the lower auditory system.

PMID- 8544879
TI  - [Drug addiction. The social medical approach to the addiction epidemic].

PMID- 8544880
TI  - [On the borderline between prescription and supply of heroin].

PMID- 8544881
TI  - [Etiology and pathogenesis of addiction].

PMID- 8544882
TI  - [Pharmacology of addiction].

PMID- 8544883
TI  - [Epidemiology of drug addiction in The Netherlands].

PMID- 8544884
TI  - [Infectious complications of drug addiction].

PMID- 8544885
TI  - [Psychiatric consequences of addiction].

PMID- 8544886
TI  - [Drug abusers and sexually transmissible disorders].

PMID- 8544887
TI  - [Opium: an old history].

PMID- 8544888
TI  - [Possibilities and limitations of drug assistance].

PMID- 8544889
TI  - [Drug abuse in Amsterdam, a public health problem].

PMID- 8544890
TI  - Biocompatibility of haemodialysis membranes: it matters in acute renal failure.

PMID- 8544891
TI  - Laboratory services utilization: a survey of repeat investigations in ambulatory
      care.
AB  - BACKGROUND: Earlier studies have shown that repeat investigations are a common
      cause of unnecessary duplication of laboratory test procedures. Most of the
      interventions aimed at reducing the number of repeat investigations have not
      resulted in long-term improvements. None of these studies, however, assessed
      utilization of laboratory services by physicians, simultaneously treating the
      same patient. METHODS: For a random sample of 1500 patients, we examined
      laboratory services utilization by physicians during an 8-month period. We
      counted the number of patients for whom more than one physician ordered
      laboratory test procedures simultaneously, and to what extent these procedures
      overlapped. RESULTS: For 28% of the patients more than one physician had ordered
      tests. Of all 41,655 tests, 5536 (13%) were repeated by a physician other than
      the physician who ordered the initial test: 1527 (4%) of the tests were repeated
      within 5 days. Patients between 70 and 90 years had the highest average number of
      tests, the highest number of involved physicians, and the smallest mean time
      between similar tests. CONCLUSIONS: There is a need for better coordination of
      care. Improved communication among physicians simultaneously treating a patient
      may lead to a reduction of repeat investigations.

PMID- 8544892
TI  - Linear IgA dermatosis: a new cause of fever of unknown origin.
AB  - We describe a 60-year-old patient who presented with prolonged fever, weight
      loss, adenopathies and malaise. Two months later, an aphthous stomatitis and
      pharyngitis developed, together with ulcerations bilaterally in the groin. Two
      separate skin biopsies revealed the diagnosis of linear IgA dermatosis. This
      entity, which is well known to dermatologists but not to internists, should be
      added to the extensive list of disorders than can provoke the syndrome of fever
      of unknown origin.

PMID- 8544893
TI  - Splenic metastasis from lung cancer.
AB  - Splenic metastasis from lung cancer is a rare clinical event, most often
      diagnosed at the time of autopsy. We report 2 cases of splenic metastasis with a
      primary lung cancer. The first case was a 76-year-old man presenting with a
      recurrent solitary splenic metastasis 14 months after surgical removal of a
      squamous cell carcinoma of the lung. The second patient was a 72-year-old woman
      who had a poorly differentiated carcinoma of the lung and multiple abdominal
      metastasis. We also investigated 267 autopsy cases of lung cancer from 1975 to
      1992. Histologically, there were 73 cases of squamous cell carcinoma, 123
      adenocarcinoma, 29 large cell carcinoma, 36 small cell carcinoma, and 7 other
      miscellaneous tumours. The number of splenic metastasis from lung cancer in these
      cases was 15 (5.6%). Splenic metastasis from a primary cancer of the left lung
      was more frequent than that from the right lung. Nine of 15 splenic metastases
      were smaller than 1 cm in size. Splenic metastasis was associated with liver and
      pancreas metastasis. All 15 autopsy cases with splenic metastasis from lung
      cancer had other abdominal organ metastasis. Our analysis indicates that a
      solitary splenic metastasis is rare. Selection of a suitable therapeutic approach
      is important.

PMID- 8544894
TI  - Respiratory failure in leptospirosis (Weil's disease).
AB  - Two patients with leptospirosis (Weil's disease), with acute respiratory failure
      necessitating mechanical ventilation, are described. Adult respiratory distress
      syndrome (ARDS) in one patient and profuse pulmonary bleeding in the other were
      the respective causes of respiratory failure. One patient died after developing
      the multiple organ dysfunction syndrome (MODS), the other patient recovered
      completely. Respiratory failure is an uncommon complication of leptospirosis and
      is due to severe pulmonary bleeding and/or ARDS.

PMID- 8544895
TI  - Liquorice-induced hypertension--a new understanding of an old disease: case
      report and brief review.
AB  - The case is described of a 40-year-old female with severe hypertension and
      hypokalaemic metabolic alkalosis, due to prolonged liquorice ingestion. The
      pseudo-aldosterone-like effects of liquorice have always been attributed to
      glycyrrhizic acid, but its biochemical substrate has remained elusive. It is now
      known that glycyrrhetenic acid, the hydrolytic metabolite of glycerrhizic acid,
      is the active component of liquorice which causes inhibition of the peripheral
      metabolism of cortisol. Cortisol binds with the same affinity as aldosterone to
      the mineralocorticoid receptor resulting in a hypermineralocorticoid condition.
      Ingestion of liquorice may therefore result in retention of sodium and water,
      hypertension, hypokalaemia, alkalosis and suppression of the renin-aldosterone
      system. The literature on liquorice-induced hypertension is briefly reviewed with
      emphasis on the biochemical features of this mineralocorticoid excess syndrome.

PMID- 8544896
TI  - Postprandial reversal of the portal venous flow in a patient with liver
      cirrhosis.
AB  - The case of a 61-year-old man with alcoholic liver cirrhosis and a hepatocellular
      carcinoma is presented. He was examined with duplex Doppler before and after a
      meal. In the fasting state a sluggish hepatopetal portal venous flow was found.
      After the meal a pendulating flow and then hepatofugal flow were found. The
      magnitude and direction of flow alternated synchronously with the action of the
      heart, suggesting a significant role for the hepatic artery in the postprandial
      reversal of portal venous flow. One year after this examination the patient died
      from the complications of decompensated cirrhosis and liver failure. At autopsy a
      large hepatocellular carcinoma was detected.

PMID- 8544897
TI  - Clinical relevance of ATP-dependent potassium channels.
AB  - Many cells are equipped with so-called potassium (K+) channels which have an
      important role in maintaining transmembrane potential. Closure of these channels
      leads to membrane depolarization, which can be followed by cell-specific activity
      such as contraction of vascular smooth muscle, or secretion of insulin from
      pancreatic beta-cells. Therefore, it is not surprising that a number of drugs
      have been introduced which influence K+ channels by either blocking or opening
      them. The treatment of type 2 (non-insulin-dependent) diabetes mellitus with
      sulphonylurea derivatives (SU), which exert their insulinotropic effect by
      closing the K+[ATP] channels of the pancreatic beta-cell, is customary. Slight
      differences are described in the insulinotropic action of the various SU. Claims
      in the past that treatment with SU increases cardiovascular mortality are not
      supported by sound evidence. SU may even reduce cardiovascular mortality by
      protecting against ventricular arrhythmias during cardiac ischaemia. K+[ATP]
      channel-opening drugs are under investigation for the treatment of essential
      hypertension and angina pectoris. They are at least as effective in achieving
      adequate blood pressure control as calcium channel blockers. The recently
      introduced coronary vasodilating drug, nicorandil, exerts its effect by two
      mechanisms of action: opening K+[ATP] channels in vascular smooth muscle cells of
      coronary arteries and activation of guanidyl cyclase by its nitro-group in these
      cells. A proarrhythmic effect of K+[ATP] channel openers has only been observed
      at very high doses, but not in the low doses used in angina pectoris and
      hypertension. In vivo no negative effect of K+[ATP]-channel-opening drugs on
      insulin secretion is found.

PMID- 8544898
TI  - Essentials of Bayesian diagnostic reasoning.

PMID- 8544899
TI  - Alzheimer pathology of patients carrying apolipoprotein E epsilon 4 allele.
AB  - A recent report suggested that brains of Alzheimer patients homozygous for APOE
      epsilon 4 show increased amyloid pathology compared to APOE epsilon 3
      homozygotes. We studied APOE allele frequencies in 73 AD patients and 38
      controls. We also investigated relation of APOE genotypes to beta/A4
      immunopositive plaques, cerebrovascular beta/A4 deposition, neurons expressing
      paired helical filaments (PHFs), and synaptophysin-like immunopositivity in 22
      neuropathologically verified AD patients. We also correlated APOE genotypes of
      definite AD patients to beta/A4 immunoreactivity in dermal vessel walls detected
      in lifetime skin biopsy samples. APOE allele epsilon 4 frequency was increased in
      AD compared to nondemented controls (0.37 vs. 0.11; p = 0.006). The number of
      beta/A4 immunoreactive plaques, PHFs-containing neurons, the degree of
      cerebrovascular beta/A4 deposition or synaptophysin-like immunoreactivity did not
      differ significantly in AD patients with or without epsilon 4. beta/A4 deposition
      in dermal vessel walls was more frequent in definite AD patients with epsilon 4
      (43%) than in patients without epsilon 4 (22%). However, the difference did not
      reach the statistical significance.

PMID- 8544900
TI  - Isolation of a phosphorylated soluble tau fraction from Alzheimer's disease
      brain.
AB  - Modified forms of tau proteins are major components of the paired helical
      filaments (PHFs) present in Alzheimer brains. In this study, tau from cytosolic
      samples obtained from normal and Alzheimer disease brains were fractionated by
      iron-chelated affinity chromatography (ICAC) to discriminate between isoforms
      phosphorylated to different extents using an stepwise pH gradient. Immunoblot
      analysis of the different fractions using antibody Tau-1 (recognizing an
      unphosphorylated epitope in tau and in PHF-tau after dephosphorylation) and
      antibody SMI 31 (recognizing a phosphorylated epitope in PHF-tau) have been
      carried out. Phosphorylated tau species (Tau 1-nonreactive and SMI 31-reactive)
      are only isolated from the Alzheimer samples at pH = 8.5. These tau species
      although having other Ser/Thr-Pro motifs susceptible of phosphorylation by
      proline-directed protein kinases are not further phosphorylated in vitro by MAP2
      kinase whereas the fraction isolated at pH 7.0, which contains
      underphosphorylated tau species, is phosphorylated. Thus, soluble tau species
      phosphorylated both at the sites constituting the Tau-1 and the SMI 31 epitopes
      are present in Alzheimer but not in normal brain cytosol and can be isolated by
      ICAC. These modifications may be a prerequisite for PHF formation.

PMID- 8544901
TI  - Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and
      histamine H2 blocking drugs.
AB  - Factors that modify onset of Alzheimer's disease (AD) may be revealed by
      comparing environmental exposures in affected and unaffected members of
      discordant twin pairs or sibships. Among siblings at high risk of AD, sustained
      use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with delayed
      onset and reduced risk of AD. After adjustment for use of NSAIDs, there was
      minimal effect on onset with reported history of any of three common illnesses
      (arthritis, diabetes, or acid-peptic disease). However, independent of exposure
      to NSAIDs, onset was unexpectedly delayed in those reporting extended use of
      histamine H2 blocking drugs. Randomized clinical trials will be needed to affirm
      the utility of these drugs for prevention, but the present findings may have
      implications for pathogenesis: because NSAIDs block the calcium-dependent
      postsynaptic cascade that induces excitotoxic cell death in NMDA-reactive
      neurons, and because histamine potentiates such events, excitotoxicity may
      deserve additional investigation in AD.

PMID- 8544902
TI  - Membrane interactions of a phosphomonoester elevated early in Alzheimer's
      disease.
AB  - Phosphoserine (L-PS) is among several phosphomonoesters found to be elevated in
      autopsied Alzheimer's disease (AD) brain tissue. To investigate the molecular
      interactions of L-PS with membrane lipid bilayers, small angle X-ray diffraction
      and high resolution differential scanning calorimetry (DSC) approaches were used
      with liposomes composed of lecithin and cholesterol. A one-dimensional electron
      density profile of a control dimyristoyl phosphatidylcholine (DMPC)/cholesterol
      lipid bilayer with a unit cell dimension of 52 A at 37 degrees C was generated
      from the X-ray diffraction data. Following incubation with 2.0 mM L-PS, a broad
      decrease in electron density +/- 4-12 A from the lipid bilayer center was
      observed concomitant with an increase in the width of the phospholipid headgroup
      electron density and a 3 A reduction in lipid bilayer width. The interactions of
      L-PS with DMPC lipid bilayers were concentration-dependent, highly affected by
      cholesterol content and reproduced in egg phosphatidylcholine/cholesterol
      liposomes. DSC analysis showed that millimolar (1.0-5.0 mM) L-PS levels decrease
      the phase transition cooperative unit size of DMPC liposomes in a highly
      concentration-dependent manner which was significantly greater in preparations
      containing cholesterol. The endotherm width at half-maximum doubled at 5.0 mM and
      1.25 mM L-PS, respectively, for DMPC and DMPC/cholesterol liposomes. These data
      provide direct evidence that elevated phosphomonoester levels modulate the
      biophysical properties of the membrane lipid bilayer which may, in turn, lead to
      altered structure/function relationships in membranes during AD.

PMID- 8544903
TI  - Chrysamine-G binding to Alzheimer and control brain: autopsy study of a new
      amyloid probe.
AB  - Chrysamine-G (CG) is a carboxylic acid analogue of Congo red, a histologic dye
      which stains amyloid. CG binds to the beta-amyloid protein of Alzheimer's disease
      (AD) in vitro and partitions into the brain of normal mice. In this study, we
      demonstrate increased binding of [14C]CG to homogenates of several regions of AD
      brain as compared to control. The total binding of CG to AD brain was
      approximately two- to three-fold that of control brain. The cerebellum could be
      used as an internal standard for each brain as CG binding to cerebellum did not
      differ between AD and control. The binding of [14C]CG correlated with numbers of
      senile plaques and neurofibrillary tangles. In addition, CG could be used to
      stain cerebrovascular amyloid in tissue sections. These results suggest that CG
      may prove useful as an in vivo probe of amyloid deposition in AD.

PMID- 8544904
TI  - PDGF is associated with neuronal and glial alterations of Alzheimer's disease.
AB  - In the present study we observed that while platelet-derived growth factor (PDGF)
      BB is exclusively expressed by neurons in the human brain, PDGF-AA is expressed
      in neurons and blood vessels. In Alzheimer's disease (AD), antibodies against
      PDGF-BB (but not PDGF-AA) recognized the neurofibrillary alterations of this
      disease. The levels of PDGF-BB correlated with the patterns of synaptic loss and
      sprouting while PDGF-AA immunostaining of the vessels was correlated with glial
      proliferation. Immunostaining was completely abolished when the antibodies were
      preincubated with their respective purified recombinant PDGF. Western blot
      analysis showed that antibodies against PDGF recognized a 31 kDa protein that was
      mildly increased in AD. These data suggest that PDGF, as well as other
      neurotrophic factors, play an important role in the mechanisms of neurofibrillary
      pathology in AD.

PMID- 8544905
TI  - Decreases in protease nexins in Alzheimer's disease brain.
AB  - A marked and significant reduction of protease nexin-1 (PN-1) and PN-2/amyloid
      beta protein precursor (A beta PP) was observed in selected regions of
      Alzheimer's disease (AD) brains as compared to those of aged-matched controls.
      Correlative analysis indicated a relationship between PN-1 reduction and the
      severity of pathologic alterations. A statistically significant inverse
      correlation was noted between the level of PN-1 activity and the density of tau
      positive dystrophic neurites in the hippocampus. In view of the ability of
      thrombin and PN-1 activity to regulate neurite outgrowth, it is possible that
      abnormal thrombin and PN-1 interactions may play a role in dystrophic neurite
      formation. The presence of clusters of dystrophic neurites around the capillaries
      suggests that blood-brain barrier (BBB) dysfunction may enhance such abnormal
      interactions. The decrease in PN-2/A beta PP levels in AD brains could possibly
      contribute to neuronal degeneration in AD in view of the ability of PN-2/A beta
      PP to protect neurons against the toxic effects of the A beta.

PMID- 8544906
TI  - Cerebral microvessels in Alzheimer's have reduced protein kinase C activity.
AB  - Protein kinase C (PKC) is an important intracellular signalling enzyme. Numerous
      studies have suggested that alterations in this enzyme occur in aging and
      dementia. The objective of this study was to examine PKC in the cerebral
      microcirculation in aging and Alzheimer's disease. PKC activity, amount, and
      isoform distribution were analyzed in microvessels from adult and aged rodents as
      well as from Alzheimer patients and nondemented elderly controls. PKC activity
      was lower in Alzheimer vessels than in vessels from control brains, despite the
      presence of similar levels of PKC enzyme. In contrast, both activity and enzyme
      levels in young and aged rats were comparable. The beta-isoform was present in
      both rat and human microvessels and there were no age- or disease-related
      alterations. The loss in activity in cerebromicrovascular PKC in Alzheimer's
      suggest that perturbations in phosphorylation signalling cascades may exist at
      the Alzheimer blood-brain barrier.

PMID- 8544907
TI  - VIP neurons in the human SCN in relation to sex, age, and Alzheimer's disease.
AB  - The brains of 46 control subjects and 21 Alzheimer's disease (AD) patients were
      studied to determine whether there are age-related or AD-related changes in the
      vasoactive intestinal polypeptide (VIP) neuron population of the human
      suprachiasmatic nucleus (SCN). The number of VIP expressing neurons in the SCN of
      females, ranging in age from 10-91 years, did not change during normal aging. In
      males, however, the number of VIP neurons in the SCN was highest in the young
      subjects (10-40 years of age), after which, a dramatic decrease occurred in
      middle-aged subjects. This resulted in an age-dependent sex difference in the VIP
      cell population of the SCN: young males had twice as many VIP expressing SCN
      neurons as young females, whereas in the middle-aged groups, the females had
      twice as many VIP SCN neurons as the males. A significant decrease in the number
      of VIP expressing neurons in the SCN was found in female presenile AD patients,
      i.e., those younger than 65 years.

PMID- 8544908
TI  - Skin vessel reactivity is impaired in Alzheimer's disease.
AB  - Fifteen patients with Alzheimer's disease (AD) and 16 age-matched controls
      underwent skin vessel reactivity tests employing three vasodilating substances
      with different modes of action: acetylcholine (ACh), nitroprusside, and
      isoprenaline. The substances were iontophoresed into the skin and the results
      were mapped through a newly developed laser Doppler perfusion imager. The skin
      vascular responses of the patients to ACh and isoprenaline but not nitroprusside
      were significantly attenuated compared to those of the controls. The differences
      between patient and control groups concerning skin vessel reactivity might be due
      to receptor/signal transduction abnormalities but might in addition indicate an
      attenuated endothelium-dependent vasodilation in AD. The results of this study
      support the hypothesis that AD might be a systemic disease. They suggest that
      tests of skin vessel reactivity might be of help in the antemortem diagnosis of
      AD.

PMID- 8544909
TI  - Constitutive Alzheimer's-type tau epitopes in a neuritogenic rat CNS cell line.
AB  - Paired helical filaments (PHFs) of Alzheimer's disease (AD) largely comprise
      hyperphosphorylated forms of the cytoskeletal protein tau. AD-type tau
      phosphoepitopes, detected by various monoclonal antibodies, are absent from
      normal adult neurons, but recent studies have shown that their expression may
      contribute to neuritogenesis and axon differentiation in the developing nervous
      system. Therefore, we have examined a brain nerve cell line that is spontaneously
      neuritogenic for possible expression of AD-type tau epitopes. The neuritogenic
      rat brain cell line B103 was found to constitutively produce two-AD related
      epitopes of tau, detected by cellular immunofluorescence studies with the PHF-1
      and Alz-50 monoclonal antibodies. Biochemical studies showed that the antibodies
      bound to proteins within the molecular, weight range expected for phosphorylated
      tau isoforms. Further verification was established by use of tau antisense
      oligomers, which eliminated cellular immunofluorescence due to the AD-related
      monoclonals and polyclonal anti-tau but did not eliminate fluorescence due to
      anti-tubulin. Cells treated with tau antisense were not neurite-free. Neurites
      that remained, however, were abnormal, generally short and wavy in appearance.
      Cellular distribution of the tau epitopes was found to be particularly
      interesting. Alz-50 recognized only cytoplasmic tau whereas PHF-1 recognized
      nuclear tau as well as cytoplasmic. Thus, the two epitopes, are morphologically
      segregated within the cell. Because subcellular segregation of tau is compromised
      in Alzheimer's disease, mechanisms that segregate AD-type phosphotau epitopes in
      B103 cells may have relevance to this neurodegenerative disorder.

PMID- 8544910
TI  - Age-related decline in MRI volumes of temporal lobe gray matter but not
      hippocampus.
AB  - The effect of normal aging on the volume of the hippocampus and temporal cortex
      was assessed cross-sectionally with quantitative Magnetic Resonance Imaging (MRI)
      in 72 healthy men, spanning 5 decades of the adult age range (21 to 70 years).
      Neither the hippocampal nor cortical white matter volumes were significantly
      correlated with age. By contrast, left and right temporal lobe gray matter
      volumes, exclusive of the hippocampal measures, each decreased with age (p <
      0.01). Volumes of temporal lobe sulcal CSF and the ventricular system (temporal
      horns and lateral and third ventricles) significantly increased with age.
      Measures of verbal and nonverbal working memory showed age-related declines and
      were related to enlargement of the three ventricular regions, which may be
      indicative of age-related atrophy of the adjacent cortex but not the hippocampus,
      at least up to age 70 years.

PMID- 8544911
TI  - A reduced calorie-high fiber diet retards age-associated decreases in muscarinic
      receptor sensitivity.
AB  - The effects of a reduced calorie-high fiber diet (RCHF) were examined on three
      cholinergic signal transduction (ST) parameters: (a) oxotremorine enhancement of
      K(+)-evoked dopamine release and (b) carbachol-stimulated low KM GTPase activity
      [an indicator of muscarinic receptor (mAChR)-G protein coupling/uncoupling], and
      (c) [3H]Quinuclidinyl benzilate (QNB) autoradiography. Comparisons were made
      among: young control (6 months), old normal control, old reduced calorie high
      fiber [both 24 months)]. The results indicated that old reduced calorie high
      fiber rats (1900 kcal/kg/day, 2.4%, lipids 2.4%, fiber 28%, carbohydrates 40.7%)
      as compared to the old normal control rats (3000 kcal/kg/day, 4.8% lipids, 4.2%
      fiber, carbohydrates 61.5%) showed a retardation of age-related deficits in
      dopamine release (a above) and GTPase activity (b above). These parameters were
      25% higher in the old reduced calorie high fiber rats as compared to old normal
      controls and did not differ from young controls, even though there was no
      increase in mAChR concentration in the restricted group. Thus, these results
      indicate that a reduced calorie high fiber diet as utilized in these experiments
      was effective in retarding the age-related decrements in two of three signal
      transduction parameters. They are discussed in terms of the induction of membrane
      changes (e.g., fluidity) or related decreases in oxidative stress by the
      restricted diet that may be involved in these signal transduction effects.

PMID- 8544912
TI  - Ovariectomy and age alter gonadotropin hormone releasing hormone-noradrenergic
      interactions.
AB  - The noradrenergic (NA) system influences gonadotropin hormone releasing hormone
      (GnRH) neurons resulting in the luteinizing hormone surge. Direct neuroanatomical
      interactions between preoptic area (POA) GnRH neuronal elements and NA [i.e.,
      dopamine-beta-hydroxylase (DBH)] terminals; effects of short-term ovariectomy (S
      OVX) on these interactions; and the stability of these interactions with age were
      studied in young (5-month-old) proestrous, 5-month-old S-OVX (6d), old (24-month
      old) constant diestrous, and 24-month-old long-term (L)-OVX mice. Proestrous
      females demonstrated direct interactions between NA terminals and GnRH neuronal
      elements. The percentage of GnRH dendritic profiles contacted by DBH terminals at
      proestrous (6.96 +/- 1.07%) did not differ versus young S-OVX females (4.55 +/-
      0.91%). No GnRH-NA interactions were observed in old mice. S-OVX resulted in a
      decrease in DBH terminals but an increase in dendrite and nonmyelinated axon
      number versus young proestrous females (p < or = 0.05 ANOVA). Findings show
      direct GnRH-DBH interactions, confirm S-OVX effects on neural ultrastructure, and
      demonstrate some S-OVX changes resembling those in older mice. L-OVX failed to
      prevent aging changes. Diminished capacity to produce normal estrous cycles in
      aging females could result in part from absence of direct GnRH-DBH interactions.

PMID- 8544913
TI  - Age-related changes in tetrahydrobiopterin and GTP-cyclohydrolase activity in the
      brain and adrenal gland of rats.
AB  - In the present study, we observed that tetrahydrobiopterin (BH4) levels were
      decreased significantly in the striatum, substantia nigra, frontal cortex,
      hypothalamus, and cerebellum of 25-month-old and in the cerebellum only in case
      of 18-month-old rats as compared to 4-month-old rats. In contrast, BH4 levels in
      adrenal glands of 25-month-old rats were increased significantly. Kinetic
      analysis of GTP-cyclohydrolase revealed a decrease in the apparent Km along with
      an increase in Vmax value in the adrenal of 25-month-old rats compared to 4-month
      old rats. Whereas, in cerebellum we observed that the apparent Km of the high
      affinity form of the enzyme was increased and a decrease in the Vmax value of the
      low affinity form only in case of 25-month-old rats compared to the young
      animals. These alterations in the BH4 levels and its synthesizing enzyme kinetics
      in specific brain areas and adrenal glands of aged rats are consistent with the
      reported changes in the catecholamine function in central and peripheral nervous
      system with aging.

PMID- 8544914
TI  - Alterations in alpha-adrenoceptors in aging intraocular hippocampal grafts.
AB  - Age-related changes of hippocampal alpha 1- and alpha 2-adrenoceptors were
      investigated using intraocular hippocampal transplants combined with 3H-prazocin
      and 3H-para-aminoclonidine (3H-PAC) autoradiography. Young hippocampal grafts in
      young hosts and old grafts in old hosts innervated by noradrenergic sympathetic
      fibers were studied. In addition, young and old hippocampal grafts were examined
      following noradrenergic denervation by superior cervical ganglion removal. The 3H
      PAC binding was significantly reduced in aged grafts as compared to young grafts
      whereas the 3H-prazocin binding did not change with age. After sympathetic
      denervation, both 3H-PAC and 3H-prazocin binding increased significantly in young
      grafts. In aged adrenergically denervated grafts, alpha 2-receptor binding was
      again significantly reduced whereas alpha 1-receptor binding was not
      significantly different from that in young denervated grafts. Taken together,
      these results indicate a selective age-related reduction in hippocampal
      postsynaptic alpha 2-receptors which is intrinsically determined.

PMID- 8544916
TI  - Age-related changes in brain and pituitary 5 alpha-reductase with finasteride
      (Proscar) treatment.
AB  - Finasteride (Proscar), a 5 alpha-reductase inhibitor, was administered with or
      without 5 alpha-dihydrotestosterone (DHT) in juvenile (28), peripubertal (48), or
      young adult (68-day-old) male rats. Luteinizing hormone (LH) levels and ventral
      prostate (VP) weights monitored the efficacy of the treatments. For each
      postnatal day tested, LH hormone levels were not significantly altered by
      finasteride, suggesting that 5 alpha-reductase inhibition does not modulate LH in
      male rats using this protocol. Finasteride plus DHT treatment significantly
      decreased LH levels. Conversely, VP weights were significantly decreased in
      finasteride-treated animals while finasteride plus DHT treatment significantly
      increased VP values. Finasteride plus DHT treatment significantly decreased
      pituitary, but not brain, 5 alpha-reductase for each postnatal day tested. In
      finasteride-treated animals, hypothalamic and pituitary 5 alpha-reductase were
      significantly inhibited in young adult animals, whereas the activities were not
      altered in juvenile or peripubertal male rats. These data suggest that a
      different mechanism may regulate 5 alpha-reductase with the aging of the central
      nervous system and pituitary.

PMID- 8544915
TI  - In vivo assessment of striatal dopamine release in the aged male Fischer 344 rat.
AB  - A microdialysis probe was implanted into the striatum of young (4- to 5-month
      old) and aged (26- to 27-month-old) Fischer 344 male rats to assess age-related
      alterations in striatal dopamine (DA) release. Basal levels of DA and the
      magnitude of DA response evoked by 50 mM and 100 mM high potassium (K+) in aged
      rats were similar to those in young rats. Furthermore, K(+)-evoked DA release did
      not correlate with motor performance within either age group. In contrast,
      amphetamine (250 microM) evoked-DA release of aged rats was significantly lower
      than that of young rats. Moreover, the enhancement of K(+)-evoked DA release by
      oxotremorine (500 microM) was significantly attenuated in aged rats. These
      results indicate that a putative DA release mechanism and its cholinergic
      modulation of the aged striatum are impaired.

PMID- 8544917
TI  - Perikaryal accumulation and proteolysis of neurofilament proteins in the post
      mortem rat brain.
AB  - Investigations of neurofilament alterations in neurodegenerative disorders
      utilize postmortem human tissues obtained at autopsy. To determine if alterations
      in the levels or distribution of neurofilament proteins might occur during the
      interval between death and autopsy, the postmortem cooling curve of the human
      brain was modeled in Sprague-Dawley rats and neurofilament proteins were examined
      by immunocytochemistry and immunoblots. One hour after death, enhanced perikaryal
      immunostaining of NF-M and both phosphorylated and nonphosphorylated NF-H
      epitopes was observed throughout the hippocampal formation. A greater number of
      neurons exhibited increased somatic immunostaining 4-h postmortem. In addition,
      loss of neurofilament protein immunostaining was observed in the neuropil,
      particularly in the molecular layer of the dentate gyrus. This corresponded with,
      but lagged behind, the pattern of calpain activation determined using an antibody
      against calpain-cleaved alpha-spectrin. Immunoblots confirmed the postmortem loss
      of neurofilament proteins in both triton-soluble and insoluble fractions. These
      results demonstrate that the levels and localization of neurofilament proteins
      observed in tissues obtained at autopsy even with short postmortem intervals may
      not accurately reflect the premortem condition.

PMID- 8544919
TI  - Oxidative stress and Alzheimer's disease.

PMID- 8544918
TI  - Are reactive oxygen species involved in Alzheimer's disease?
AB  - Alzheimer's disease has a multifactorial pathogenesis. Among the various factors
      involved, this review examines, in particular, the possibility of oxidative
      stress, meaning an imbalance between the formation and spread of reactive oxygen
      species (ROS) and the antioxidant defenses. This theory is supported by the
      following observations: (a) the alteration of mitochondrial function, which is
      likely to lead to the electron leakage in the respiratory chain and the
      consequent formation of superoxide radicals; (b) the unbalanced high activity of
      superoxide dismutase and monoamine oxidase B which causes the production of more
      H2O2; (c) the alteration of iron homeostasis which, in combination with the
      superoxide and H2O2, gives rise to the most deleterious hydroxyl radicals; (d)
      the increased lipid peroxidation and membrane alterations; (e) the pro
      aggregating effect of ROS on beta/A4 protein and the C-terminal fragment of
      amyloid precursor (A4CT). Most of these changes are already present in the normal
      aging brain but are aggravated in AD presumably over a number of years. However,
      further investigations are needed to confirm these theories particularly
      regarding the alterations of another target of ROS, the proteins. Peroxidative
      stress is presumably present in the AD brain. This stress might not be a primary
      factor in the pathogenesis of AD, but a consequence of the tissue injury. In any
      case, it could contribute considerably to the pathology, in a vicious cycle of
      actions and reactions resulting in a critical mass of metabolic errors,
      responsible in the end for this disease.

PMID- 8544920
TI  - Free radicals and disruption of neuronal ion homeostasis in AD: a role for
      amyloid beta-peptide?

PMID- 8544922
TI  - New hopes arise with the transgenic model for Alzheimer's disease.

PMID- 8544921
TI  - Mutant and native human beta-amyloid precursor proteins in transgenic mouse
      brain.
AB  - Human beta-amyloid precursor protein (beta APP) has been targeted to transgenic
      neurons using synapsin I promoter-based chimeric transgenes. Native human beta
      APP was introduced as well as beta APP containing mutations genetically linked to
      familial Alzheimer's disease (AD) and to hereditary cerebral hemorrhage with
      amyloidosis-Dutch type. In mouse brain, human beta APP RNA was up to 60% as
      abundant as total endogenous beta APP RNA. Human beta APP gene expression was
      most abundant in the CA subfields of the hippocampus and in the piriform cortex.
      Correct processing of human beta APP at the beta-secretase cleavage site was
      demonstrated in transgenic mouse brains. Despite a 40% increase in total beta APP
      immunoreactivity in lines expressing mutant human beta APP, no evidence of
      amyloid deposition was found in brains of mice up to 14 months in age. Higher
      levels of mutant human beta APP, increased age, or other factors may be necessary
      to elicit beta-amyloid-related neuropathologies in the rodent brain.

PMID- 8544923
TI  - Understanding the biology of beta-amyloid precursor proteins in transgenic mice.

PMID- 8544924
TI  - Striving for useful phenotypes in beta-APP transgenic mice.

PMID- 8544925
TI  - The potential utility of transgenic mice harboring beta-amyloid precursor
      protein.

PMID- 8544926
TI  - [Own experience with botulinum treatment of dystonia].
AB  - Fifty-five patients were treated with botulin injections into the muscles showing
      dystonia, contracture or tremor. Twenty two of them had torticollis, 21 had
      blepharospasm, 10 had hemifacial spasm, and 2 had tremor. In all, 112 injections
      were done with good result in 64%, slight effect in 27% and without effect in 9%
      of the cases. Similar results have been reported from other centers in the world.
      Adverse effects were not significant and disappeared after several days or weeks.
      They included ptosis, speech and deglutition disturbances, general weakness and
      neurotic reactions. These adverse effects developed in 12 cases. In cases of
      tremor the dose as well as the technique of injections must be individualized.
      The method is an important therapeutic advance and can be applied in outpatient
      clinics.

PMID- 8544927
TI  - [Transcranial Doppler ultrasonography and hyperventilation test in assessment of
      cerebral vasoreactivity after ischemic stroke].
AB  - In 36 patients 3 month after ischaemic stroke in regions supplied by MCA (Middle
      Cerebral Artery) physical examination, CT scanning and blood flow velocity
      recordings in ICA (Internal Carotid Artery) and MCA were performed. In both MCA
      blood flow velocity was measured in resting state and after 30 sec. of
      hyperventillation. The control group consisted of 40 healthy volunteers. In the
      control group blood flow decrease after hyperventillation was nearly equal in
      both hemispheres (38% in right and 37% in the left hemisphere). In studied group
      in the symptomatic hemisphere blood flow reduction was 21%. Vasoreactivity in the
      opposite hemisphere was similar to that in control group (35% decrease). The
      results suggest that vasoreactivity diminution is a local phenomenon limited to
      the infarcted area. Hyperventilation test, despite its simplicity, seems to be
      sufficient for screening vasoreativity.

PMID- 8544928
TI  - [Effect of intravenous glucose load on blood glucose and fructose level and
      glucose-6-phosphate isomerase activity in serum of patients with acute
      cerebrovascular disease in its earliest phase].
AB  - The purpose of the study was to investigate the dynamics of glucose and fructose
      concentrations in the blood changes and phosphohexose isomerase activity (PHI) in
      serum of unfed or after intravenous glucose injection patients, with acute
      cerebrovascular disease in the earliest period of illness. The investigation was
      done in 15 patients with transient ischaemic attacks, 30 patients with cerebral
      ischaemic stroke and 15 patients with cerebral haemorrhage. In patients with
      different forms of acute cerebrovascular damage it was found that there was
      hyperglycaemia in the blood of unfed patients, elevated blood fructose level and
      increased serum PHI activity; those changes were increased by intravenous glucose
      administration. The changes were most expressed in the group of patients with
      cerebral haemorrhage and cerebral ischaemic stroke.

PMID- 8544929
TI  - [Malonic dialdehyde concentration in cerebrospinal fluid as an indicator of the
      intensity of lipid peroxidation processes in intracranial hypertension].
AB  - The authors of the study correlate malonic dialdehyde (MDA) concentration in the
      cerebrospinal fluid of infants with hydrocephalus with the values of intracranial
      pressure. The purpose of the study was verification of the usefulness of MDA
      concentration determination as an indicator of the processes of lipid
      peroxidation in CNS tissues in hydrocephalic children. The obtained results point
      out that the isolated MDA concentration is not a sufficiently precise marker of
      intracranial hypertension.

PMID- 8544930
TI  - [Assessment of radiographic investigation in discopathy diagnosis].
AB  - Based on 262 radiographic examinations done during two years the authors have
      analyzed the compatibility of the radiographic image with the clinical
      examinations and with the operation results. In the analysis the most frequently
      occurring lesion level having the character of hernia of the nucleus pulposus,
      age, sex, and the duration of the disease symptoms were taken into account. The
      effectiveness of the method, which was verified by surgery was 86.3%. The result
      is in good agreement with literature data. Therefore, the method can be still
      recommended, particularly for the x-ray laboratories, which have no possibility
      to apply non-invasive techniques.

PMID- 8544931
TI  - [Study of the effect of biogonadyl on the regeneration of the rat's sciatic
      nerve].
AB  - Using electroneurographic and morphological methods the effect of Biogonadyl on
      the regeneration of sectioned and the sutured sciatic nerves was evaluated. The
      analysis of conduction parameters in the sciatic nerves during the 6-week
      experiment, although the results obtained were not statistically significant,
      suggests a beneficial effect of Biogonadyl upon regeneration processes in the
      nerves. Morphological and morphometric studies have demonstrated that Biogonadyl
      statistically significantly accelerated axon growth in the distal part of sciatic
      nerves. It did not, however, influence the processes of their maturation.

PMID- 8544932
TI  - [The level of Interleukin-6 in patients with amyotrophic lateral sclerosis].
AB  - The role of immune factors in the pathogenesis of ALS is taken into account and,
      in view of this, it was decided to study the role of interleukins (IL) taking IL
      6 as an example. Its concentration was determined in blood and CSF with Amersham
      RIA kits. The study was carried out on 16 ALS patients and 16 patients with low
      back pain who served as controls. The IL-6 level in blood and CSF did not vary
      between these groups statistically significantly. Then from the ALS group the
      cases with only bulbar symptoms or with predominance of bulbar symptoms were
      isolated. This subgroup comprised 6 patients, their mean age was higher, and
      disease duration was shorter. The IL-6 level in the CSF was 27.1 +/- 8.6 nmol/ml
      and was statistically significantly higher than in the remaining cases. The
      specificity of this finding is discussed.

PMID- 8544933
TI  - [Thoracic outlet syndrome: results of surgical treatment].
AB  - 21 patients with thoracic outlet syndrome (t.o.s.) were operated on in the
      Department of Neurosurgery of MMA in Lodz between 1982-1991. Early and long-term
      results of treatment were analyzed in the group of 13 cases. In early
      postoperative period 5 patients were free of pain and neurologic or vascular
      disturbances in the upper limb. In other 6 cases pain disappeared partially and
      mild neurological or vascular syndromes persisted. Altogether satisfactory
      results of treatment were obtained in 8 patients (85%). There was some
      improvement in 2 patients but pain and neurological or vascular disorders were
      still significant after surgery. Long-term results were assessed at least 1 year
      after operative treatment. Recurrent pain with or without mild neurological
      (vascular) syndromes appeared in 6 patients (46%). Recurrent t.o.s. occurred
      mainly in cases of young women with low position of shoulder girdle and poorly
      developed musculature of this region. Only 2 patients still remained free of
      preoperative syndromes. Altogether only 8 patients (61%) had acceptable results
      of surgical treatment at long-term follow-up. The remaining 5 patients (39%) had
      unsatisfactory long-term results.

PMID- 8544934
TI  - [Latest results of surgical treatment of vertebrobasilar aneurysms].
AB  - The author presents late results of surgery of 65 vertebrobasilar aneurysms (out
      of 100 patients treated operatively). The data were obtained from 50 patients
      (76.9% of all investigated). In spite of large number of independent patients
      (41), only 9 returned to previous work, and 6 changed their occupation, but 32
      received disability pensions.

PMID- 8544935
TI  - [The role of enzymatic systems in pathophysiology and pharmacotherapy of
      Parkinson's disease].
AB  - In the metabolism of one of the main CNS neurotransmitters dopamine very
      important roles are played by four enzymes: two synthetizing dopamine: TH and
      DDC, and two enzymes breaking down dopamine: MAO-B and COMT. In a short review
      the author discusses disturbances of these enzymatic systems in parkinsonism and
      therapeutic possibilities of using drugs stimulating or inhibiting the activity
      of these systems.

PMID- 8544936
TI  - [Clinical and genetic heterogeneity of limb-girdle muscular dystrophy].
AB  - Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of dystrophies in
      which weakness and wasting initially appear at proximal groups of pelvic and
      shoulder girdles. Families in which LGMD is inherited as an autosomal recessive
      and rarely autosomal dominant trait were separated. Among autosomal recessive
      families, cases with rapid progression, called severe childhood autosomal
      recessive muscular dystrophy (SCARMD) were isolated. In some of these families
      linkage to chromosome 13 has been demonstrated. In other families especially
      those with relatively slower progression the genes were localised on chromosomes
      2, 15. In families with adhalin mutations variability of clinical presentation is
      observed. In one of the described families with autosomal dominant inheritance
      the linkage to chromosome 5 has been established. Clinical and genetic studies of
      a large cohort of patients with limb-girdle muscular dystrophies enables the
      creation of new LGMD diagnostic criteria which facilitates proper genetic
      counselling.

PMID- 8544937
TI  - [Diagnosis of the upper thoracic outlet syndrome].
AB  - Basing on a review of literature and own experience the authors present the
      aetiology and various diagnostic methods of thoracic outlet syndrome (t.o.s.),
      especially electrodiagnostic and Doppler studies. Provocative tests like Wright,
      Adson or hyperabduction manouvers are discussed and their role in modern
      diagnosis of t.o.s. is presented.

PMID- 8544938
TI  - [Investigation of cerebrovascular reactivity using transcranial doppler
      ultrasonography].
AB  - Transcranial Doppler ultrasonography (TCD) is the most useful method for
      evaluation of relative changes of cerebral blood flow. This features was used in
      the investigations measuring cerebrovascular reactivity for physiological and
      pathological impulses.

PMID- 8544939
TI  - [Two cases of neuroboreliosis: Lyme disease].

PMID- 8544940
TI  - [Newly formed intracranial saccular aneurysms revealed within several years after
      surgery for the aneurysm with different localization: report of 2 cases].
AB  - The authors present two patients treated surgically for intracranial aneurysms.
      Within 2.5 and 4.6 years after surgery the repeated angiography performed after
      the second SAH revealed newly formed aneurysms in another localisation. These
      facts became a contribution to the etiopathogenetic considerations.

PMID- 8544941
TI  - [Difficulties in the diagnosis of cerebral abscess in a 15-year old boy with von
      Recklinghausen disease treated surgically: recovery case report].
AB  - A case of neurofibromatosis type 1 in 15 years old boy is presented. Recurrent
      intracranial bleedings, epileptic seizures and brain abscess were the main
      manifestations of the disease. The authors suggest that hamartomatous cerebral
      lesion with vascular abnormalities might be responsible for such a picture of the
      disease.

PMID- 8544942
TI  - [Comment on the article by R. Kaczmarczyk et al. in Neurologia i Neurochirurgia
      Polska No. 5/94].

PMID- 8544943
TI  - [Comment on the article by E. Czestochowska and B.L. Imielinski in Neurologia and
      Neurochirurgia Polska, No. 2:95].

PMID- 8544944
TI  - Effect of histamine on gene expression and release of proopiomelanocortin-derived
      peptides from the anterior and intermediate pituitary lobes in conscious male
      rats.
AB  - Via activation of H1 or H2 receptors histamine (HA) stimulates the secretion of
      proopiomelanocortin (POMC)-derived peptides from the anterior (AL) and
      intermediate (IL) pituitary lobes of male rats. During selective inhibition of
      the AL or IL by pretreatment with dexamethasone (Dx) or bromocriptine (Br),
      respectively, we studied the effect of equipotent doses of
      intracerebroventricularly infused HA, the H1-receptor agonist 2
      thiazolylethylamine (2TEA) or the H2-receptor agonist 4-methy1HA (4MeHA) on the
      release of ACTH, beta-endorphin (beta-END) immunoreactivity (ir) and alpha
      melanocyte-stimulating hormone (alpha-MSH) in conscious male rats. Dx blocked the
      ACTH responses whereas Br prevented the alpha-MSH responses. Dx and Br equally
      inhibited the response of beta-ENDir to HA and 4MeHA (80 and 70%, respectively).
      In contrast, the beta-ENDir response to 2TEA was totally blocked by Dx but only
      inhibited 50% by Br. The inhibitory effect of Dx on the beta-ENDir response to
      2TEA was significantly stronger than the effect on the responses to HA and 4MeHA.
      POMC mRNA in the AL but not in the IL was increased almost 45% by HA and 2TEA and
      20% by 4MeHA. Since all three histaminergic compounds in the doses used
      stimulated the release of beta-ENDir equipotently, the results indicate that H1
      receptor activation predominantly affects the release and synthesis of beta-ENDir
      from the AL while H2-receptor activation affects the release of beta-ENDir
      equally from the two lobes and only to some extent increases the synthesis in the
      AL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544945
TI  - Endogenous excitatory amino acids are involved in stress-induced
      adrenocorticotropin and catecholamine release.
AB  - The effect of N-methyl-D-aspartic acid (NMDA) receptor blockade on
      adrenocorticotropin (ACTH) and catecholamine activation during stress was
      investigated in conscious rats with indwelling catheters for both blood sampling
      and drug treatment. Secretion of ACTH in response to immobilization stress (20
      min) was inhibited by pretreatment (20 min before stress exposure) with the
      centrally acting noncompetitive antagonist of NMDA receptors MK-801 (dizocilpine,
      the racemic form, 1 mg/kg i.p.) but not by 3-[(+/-)-2-carboxypiperazin-4
      yl]propyl-1-phosphonic acid (CPP; 10 mg/kg i.p.), a competitive NMDA receptor
      antagonist. Administration of MK-801 (1 mg/kg i.p.) inhibited norepinephrine and
      totally prevented epinephrine response during acute immobilization stress.
      Pretreatment with a low dose of MK-801 (0.1 mg/kg i.p.) failed to modify basal or
      stress-induced ACTH and catecholamine release. The stress-induced rise in plasma
      epinephrine was found to be attenuated by the peripherally injected competitive
      antagonist CPP (10 mg/kg i.p.) suggesting that modulation not only of central but
      also of peripheral NMDA receptors may come into play. Our results indicate the
      involvement of endogenous excitatory amino acids in the control of ACTH and
      particularly of epinephrine secretion during stress.

PMID- 8544946
TI  - Stimulation of the amygdala by glutamate facilitates corticotropin-releasing
      factor release from the median eminence and activation of the hypothalamic
      pituitary-adrenal axis in stressed rats.
AB  - The role of the amygdala in the regulation of hypothalamic release of
      corticotropin-releasing factor (CRF) was investigated. Microinjection of
      glutamate (50 nmol) into the amygdala resulted in increased plasma corticosterone
      in male rats previously subjected to a 14-day unpredictable stressor paradigm (p
      < or = 0.05 vs. saline-injected controls). A long-lived increase in
      corticosterone levels was also observed in rats which were urethane-anesthetized
      (1.35 g/kg) 3 h prior to glutamate microinjection (p < or = 0.01 vs. saline
      injected controls). These effects on plasma corticosterone were observed despite
      the presence of high basal levels of corticosterone. Furthermore, microperfusion
      of glutamate (3-300 microM) into the amygdala of urethane-anesthetized rats
      resulted in a dose-dependent increase in CRF release from the median eminence, as
      assessed by in vivo microdialysis (p < or = 0.025 vs. basal). These results
      indicate a facilitating role for the amygdala in stress-induced increases in CRF
      release and subsequent adrenocortical activation.

PMID- 8544947
TI  - Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at
      high familial risk for affective disorders.
AB  - Altered negative feedback control of the hypothalamic-pituitary-adrenocortical
      (HPA) system is a frequent laboratory sign of major depression. It coincides with
      depressive episodes and partially reverses after recovery from psychopathology.
      Such an HPA disturbance in feedback control can be acquired as a result of
      stressful life experiences and be compounded by age or it can be genetically
      predetermined at all levels involved in fine-tuned neuroendocrine regulation.
      Major psychiatric disorders run in families and a high familial load for an
      affective illness therefore increases an individual's risk of becoming affected.
      We investigated whether the HPA feedback disturbance observed among patients with
      depression is present in otherwise healthy individuals who are at high risk for
      psychiatric disorders because they have a first-degree relative with an affective
      illness. Using rigid psychodiagnostic techniques, we screened 431 consecutively
      admitted patients with depression and identified 35 families with one or more
      high-risk probands (HRPs). The results of a combined dexamethasone/human
      corticotropin-releasing hormone (DEX-CRH) test showed that the group of
      dexamethasone-pretreated (1.5 mg; 23.00 h) HRPs released more cortisol after
      stimulation with human CRH (100 micrograms; 15.00 h the next day) than a control
      group (CPs), but less than a group of patients with an acute major depressive
      episode (DPs). The peak cortisol values were 146.1 +/- 147.7 nmol/l (mean +/- SD)
      (HRPs), 75.3 +/- 47.9 nmol/l (CPs) and 278.2 +/- 199.2 nmol/l (DPs), yielding
      significant (F = 9.66, p < 0.001) group differences, with values for HRPs vs. CPs
      and HRPs vs. DPs being significant at the 1% level (t test).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8544948
TI  - Repeated endotoxin treatment decreases immune and hypothalamo-pituitary-adrenal
      axis responses: effects of orchidectomy and testosterone therapy.
AB  - It is known that in vivo administration of bacterial endotoxin activates immune
      cells to release cytokines, these substances in turn enhancing hypothalamo
      pituitary-adrenal (HPA) axis function; additional evidence supports the existence
      of an immune-neuroendocrine sexual dimorphism. In the present study, we
      investigated: (1) the in vivo response of both the HPA and the immune systems to
      single and repeated endotoxin administrations in mice, and (2) whether
      testosterone possesses a modulatory effect on neuroendocrine-immune function
      under endotoxemia. For these purposes, adult male BALB/c mice were
      orchidectomized (Odx) or sham-operated and injected s.c., on alternate days, with
      either corn oil alone (Odx and Sham) or containing 20 micrograms of testosterone
      (Odx+T) until animals were killed. One week after surgery, different groups of
      mice were treated i.p. with bacterial lipopolysaccharide (LPS; 25 micrograms per
      mouse) in a single (day 1, D1) or repeated (at 24-hour intervals for 5
      consecutive days) form. Animals were decapitated (on D1, D3 and D5 of the
      treatment) 2 h after the last injection of either vehicle alone or containing LPS
      (the two groups were run in parellel). Trunk blood was collected and the whole
      medial basal hypothalamus (wMBH), the anterior pituitary (AP) and adrenal glands
      were dissected. Plasma tumor necrosis factor-alpha (TNF alpha), ACTH and
      corticosterone (B) concentrations as well as wMBH CRH, AP ACTH and adrenal B
      contents were determined by specific assays.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544950
TI  - Rat interleukin-1 beta binding sites in rat hypothalamus and pituitary gland.
AB  - In this study, radiolabeled recombinant rat interleukin-1 beta (r125I-IL-1 beta)
      was used to localize and characterize IL-1 beta binding in rat hypothalamus and
      pituitary gland by quantitative autoradiography. The ability of this ligand to
      bind to type I IL-1 receptor was first tested on murine lymphoma cells (EL-4). In
      the rat-tissue sections, high densities of specific r125I-IL-1 beta binding sites
      were localized in the anterior as well as the posterior pituitary and in the
      choroid plexus. A fine labeling was observed in meninges and third ventricle
      walls while no binding was detected in the hypothalamic nuclei. Saturation
      experiments, in the anterior and posterior pituitary, revealed one specific
      binding site with an affinity constant (Kd) of 0.5 nM. Competition experiments
      were achieved using either rat IL-1 beta (rIL-1 beta) or human IL-1s (hIL-1
      alpha, hIL-1 beta and IL-1 receptor antagonist: hIL-1a). Affinity constants (Ki)
      were drastically different according to the ligand used, while Ki values were
      found similar in anterior and posterior pituitary. Competition with rIL-1 beta
      revealed one binding affinity (Ki of 0.1 nM range). In contrast, competition with
      hIL-1 beta revealed two binding affinities: a high (Ki: 0.1 pM range) and a low
      one (Ki: 1 nM range). Competition with hIL-1ra was obtained for high
      concentrations only (Ki: 10-100 nM range), whereas human IL-1 alpha (hIL-1 alpha)
      was unable to compete at 1-100 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544949
TI  - Hormonal modulation of Epstein-Barr virus replication.
AB  - Among the various factors thought to be associated with the reactivation of
      latent herpesviruses is psychological stress. An increase in levels of 'stress
      hormones' such as glucocorticoids occurs in individuals who are stressed and
      previous studies have shown that glucocorticoid hormones can reactivate latent
      Epstein-Barr virus (EBV) in vitro. In this study, we confirm that the EBV genome
      in latently infected lymphoblastoid cells can be reactivated with two
      glucocorticoid hormones, hydrocortisone and dexamethasone. In addition to
      hydrocortisone and dexamethasone, we also found that other hormones of the
      hypothalamic-pituitary-axis (corticotropin-releasing factor and
      adrenocorticotropin hormone but not epinephrine and norepinephrine) as well as
      somatostatin can enhance the lytic replication of the HR-1 strain of EBV in
      superinfected cells. These results suggest that multiple endocrine interactions
      may be involved in stress-induced reactivation/replication of latent EBV.

PMID- 8544952
TI  - Interactions with males promote rapid changes in gonadotropin-releasing hormone
      immunoreactive cells.
AB  - It is well known that hormones can regulate behaviors. However, the reciprocal
      interaction, the effects of behavior on hormones, has received less direct
      experimental attention. Dramatic changes in hormones and behaviors occur at
      puberty and some of these changes can be triggered by modification of the social
      environment. Interactions with males accelerate production of pulsatile release
      of gonadotropins and steroid hormones which, in turn, initiate estrous cycles,
      ovulation, and sexual behavior in females. Ultimately all of these actions are
      controlled by changes in production and secretion of gonadotropin-releasing
      hormone (GnRH). Little is known about how behavior affects GnRH-producing
      neurons. In female musk shrews, the first mating initiates the onset of puberty.
      Musk shrews lack a behavioral estrous cycle and they become receptive within
      minutes after their first contact with a male. As soon as 1 h after interactions
      with males there is a significant increase in the numbers of GnRH-immunoreactive
      (GnRH-ir) neurons in specific brain regions. In the present study, we examined
      changes in GnRH-ir cell number during the initial mating bout. We found dynamic
      changes in the numbers of GnRH-containing cells, correlated with changes in
      behavior. Interactions with males for less than 30 minutes induced a significant
      increase in GnRH-ir neurons in specific olfactory-related forebrain nuclei. At
      the end of a mating bout, numbers of GnRH-ir neurons declined. Because behavioral
      interactions have rapid and pronounced effects on the neurons that produce GnRH,
      this model can be used to examine the behavioral regulation of neuronal
      plasticity.

PMID- 8544951
TI  - Patterns of induction of the immediate-early genes c-fos and egr-1 in the female
      rat brain following differential amounts of mating stimulation.
AB  - Vaginocervical stimulation received either during mating or by artificial
      mechanical means has been shown to induce FOS expression in medial amygdala,
      preoptic area, hypothalamus, and midbrain of female rats. While mating-induced
      increases in FOS-like immunoreactivity (FOS-IR) have been shown to require
      intromissive stimulation from males, the pattern of FOS-IR in animals receiving
      numbers of intromissions across a range relevant to the induction of the
      prolactin surges of early pregnancy has not been explored. Experiment 1 examined
      brain FOS-IR following 15 mounts without intromission or 5, 10, or 15
      intromissions in ovariectomized females treated with estrogen and progesterone;
      these treatments are known to be less than or more than sufficient to trigger
      prolactin surges in cycling females. FOS was expressed in a graded fashion in the
      medial amygdala with respect to the numbers of intromissions received and in an
      all-or-nothing manner in preoptic area, bed nucleus of the stria terminalis, and
      ventromedial nucleus of the hypothalamus. In experiment 2, 15 intromissions
      induced expression of another immediate-early gene, egr-1, in each of these same
      areas as well as in a second division of the bed nucleus of the stria terminalis
      and in the paraventricular nucleus of the hypothalamus. These studies demonstrate
      that mating is differentially effective in inducing FOS expression in responsive
      brain areas and point to the medial amygdala as a site in which summation of
      intromissive stimulation may occur. Furthermore, the induction of EGR-1 may be a
      more sensitive marker for mating-induced neural activation in these areas than is
      FOS.

PMID- 8544953
TI  - Endogenous reproductive hormones and nocturnal rhythms in partner preference and
      sexual behavior of ATD-treated male rats.
AB  - Male rats received subcutaneously silastic capsules, containing the aromatase
      inhibitor 1,4,6-androstatriene-3,17-dione (ATD), shortly after birth. Control
      males were given silastic capsules containing cholesterol. The capsules were
      removed at the age of 21 days. In adulthood, blood serum was collected early and
      late in the dark phase of the light/dark cycle (experiment I). Testosterone and
      luteinizing hormone and follicle stimulating hormone (FSH) fluctuated
      nocturnally, both in ATD and control males, with highest levels late in the dark
      phase. FSH levels were significantly higher in ATD males. Nocturnal levels of
      inhibin, a selective suppressor of pituitary FSH secretion, also fluctuated in
      both ATD and control males, with lowest levels late in the dark phase. In
      experiment II, ATD and control males were tested for partner preference behavior
      in a three-compartment box (choice: sexually active male vs. estrous female)
      early and late in the dark phase. When gonadally intact, ATD males, but not
      controls, showed a clear nocturnal rhythmicity in partner preference behavior and
      sexual behavior. Early in the dark phase, such ATD males preferred the vicinity
      of and interaction with a sexually active male. Late in the dark phase, this
      preference for the active male shifted to a preference for the estrous female.
      Control males preferred the estrous female. After castration and subsequent
      treatment with testosterone via silastic capsules, which ensured constant blood
      serum levels, ATD males continued to show their nocturnal rhythms in partner
      preference behavior and in sexual behavior. Thus, the underlying mechanism of the
      nocturnal rhythmicity phenomenon is an organizational effect of neonatal ATD
      treatment rather than an activational effect of fluctuating serum hormone levels.

PMID- 8544954
TI  - Neurophysiological effects of vasotocin and corticosterone on medullary neurons:
      implications for hormonal control of amphibian courtship behavior.
AB  - Research on a wide variety of vertebrates, from fish to mammals, reveals that
      corticosteroid hormones and vasotocin-like neuropeptides can potently modulate
      reproductive behaviors. But, it is not clear how the behavioral effects of these
      chemical messengers relate to functional properties of behavior-controlling
      neurons. This problem was investigated in the roughskin newt, Taricha granulosa,
      an amphibian in which the administration of arginine vasotocin (AVT) facilitates
      and corticosterone (CORT) inhibits courtship clasping of females by males. In
      waking, immobilized male newts, neurophysiological effects of AVT and CORT were
      studied in neurons in the rostral medulla due to the probable role of these
      neurons in the control of clasping. Topical medullary application of a clasp
      facilitating dose of AVT produced a rapid increase in neuronal responsiveness to
      pressure on the cloaca, a trigger stimulus for clasping responses. Neuronal
      responses to noncloacal somatic stimuli and to moving visual stimuli were also
      enhanced. Systemic CORT administration, which has previously been shown to
      depress newt medullary neuronal sensory responsiveness, reversed the action of
      AVT such that the peptide depressed sensory responsiveness when applied 30 min
      after CORT. When AVT application preceded CORT injection by 10-17 min, however,
      the usual suppressive CORT effect was reversed and this treatment resulted in a
      rapidly appearing potentiation of neuronal activity and enhanced somatic sensory
      responsiveness. If the interval between AVT and CORT was increased to 30 min, the
      steroid caused a rapid depression of firing and a diminished somatic sensory
      responsiveness in most neurons, similar to what occurs in newts treated with CORT
      alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544955
TI  - Role of endogenous CRF in the mediation of neuroendocrine and behavioral
      responses to calcitonin gene-related peptide in rats.
AB  - In the present study, the possible role of cortocotropin-releasing hormone (CRF)
      in the action of calcitonin gene-related peptide (CGRP) on the pituitary-adrenal
      axis and open-field activity of rats was tested. CGRP administered into the
      lateral brain ventricle led to a dose-dependent increase in plasma corticosterone
      level, which could be blocked by pretreatment with CRF antiserum. CGRP injected
      into the lateral brain ventricle increased the grooming and rearing activity and
      decreased the locomotor activity in an open field. On pretreatment with CRF
      antiserum, the action of CGRP on grooming was blocked, while the action on
      locomotion and rearing activity was unchanged. The results suggest that the CGRP
      induced action on pituitary-adrenal activation is mediated by CRF. The action of
      CGRP on grooming in an open field is related to the pituitary-adrenal activation,
      and either CRF or adrenocorticotropic hormone or both may be involved in
      mediating the action of CGRP. The action of CGRP on rearing and locomotion is not
      affected by CRF antiserum, indicating that the two behavioral actions are
      regulated by different mechanisms.

PMID- 8544956
TI  - Hypoxic ischaemic encephalopathy: early magnetic resonance imaging findings and
      their evolution.
AB  - Eighteen term infants with hypoxic ischaemic encephalopathy (HIE) were studied
      with serial magnetic resonance imaging of the brain for up to two months
      following birth. Important early findings included brain swelling, cortical
      highlighting, diffuse loss of grey/white differentiation and loss of signal in
      the posterior limb of the internal capsule (PLIC). These signs were easier to
      identify on T1-weighted spin echo or inversion recovery sequences than on T2
      weighted spin echo sequences. Brain swelling was only seen in the first seven
      days and was present in all grades of HIE. All other signs persisted and were
      associated with the subsequent development of major structural changes in the
      brain. The exact pattern of injury was best identified after the first week of
      life once the signs of brain swelling had cleared.

PMID- 8544957
TI  - The predictive value of elevation in specific serum enzymes for subsequent
      development of hypoxic-ischemic encephalopathy or intraventricular hemorrhage in
      full-term and premature asphyxiated newborns.
AB  - Serum lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), and
      hydroxybutyrate dehydrogenase (HBDH) activities are significantly elevated in
      asphyxiated newborns within the first days of life. The approach of the present
      study was to evaluate firstly if serum levels of these enzymes correlate with the
      development of hypoxic-ischemic encephalopathy (HIE) and periventricular
      intraventricular hemorrhage (PIVH) in full-term and premature asphyxiated
      newborns, and secondly if postnatally elevated enzyme activities could be
      predictive for these disorders. ASAT, LDH and HBDH activities were measured in 98
      asphyxiated newborns. Blood samples were taken serially at five fixed times: 0
      (cord), 12, 24, 72, and 144 hours post partum. All newborns were examined for the
      development of HIE and PIVH using standardized scoring systems. Fifty percent of
      the newborns were full-term and 50% were premature. Ten of the full-term (20.4%)
      and 21 (42.8%) of the premature newborns developed HIE. Nineteen newborns (19.4%)
      suffered PIVH (full-term/premature, 7/12). The full-term asphyxiated newborns
      with HIE or PIVH showed significantly elevated ASAT, LDH, and HBDH activities
      within the first 72 hours of life. In case of the premature asphyxiated newborns,
      the enzyme activities did not differ significantly between the study groups. The
      overall predictive values showed a high sensitivity (HIE/PIVH, 90.0%/71.4%), a
      high specificity (71.0%/88.1%), an acceptable negative predictive value
      (44.9%/50.0%), and a high positive predictive value (96.5%/94.9%) for the
      development of HIE and PIVH in full-term asphyxiated newborns. It is concluded
      that measurements of ASAT, LDH, and HBDH activities are reliable predictors for
      the development of HIE and PIVH in full-term asphyxiated newborns.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8544958
TI  - In-vivo NMR spectroscopy in patients with phenylketonuria: changes of cerebral
      phenylalanine levels under dietary treatment.
AB  - Localized proton magnetic resonance spectroscopy at short echo times was used to
      measure phenylalanine (Phe) in parieto-occipital periventricular brain. Six
      treated adult patients with phenylketonuria were investigated repeatedly
      following reinstitution of a Phe-restricted diet. Difference spectroscopy clearly
      enabled the identification of elevated cerebral Phe levels by subtracting spectra
      obtained from healthy volunteers. Estimates of absolute brain concentrations
      always yielded values well below the serum levels with ratios
      [Phe]brain/[Phe]serum ranging from 0.27 to 0.63. A plot of [Phe]brain versus
      [Phe]serum could be fitted to a straight line (R = 0.90) if [Phe]serum was below
      1.3 mM. Measurements at higher serum levels could only be performed in one
      patient and yielded brain Phe concentrations of 0.63 +/- 0.10 mM suggesting a
      saturation of the carrier systems. The feasibility to quantify Phe transport
      across the blood-brain barrier in humans non-invasively employing in-vivo proton
      spectroscopy can effectively improve the prognostic significance of serum data.

PMID- 8544959
TI  - Enzyme infusion therapy of the Norrbottnian (type 3) Gaucher disease.
AB  - We report our experience from enzyme infusion therapy of eight patients with the
      Norrbottnian type of Gaucher disease (type 3) aged 4 to 42 years. All patients
      responded with increased well-being, decreased liver and spleen size and
      normalized hematological parameters. The children caught up in growth. No further
      neurological deterioration occurred and there were some indications of
      neurological improvement. Circulating glucosylceramide concentrations seemed to
      be a possible parameter to monitor the dosage of infused enzyme. The circulating
      glucosylceramide levels responded better in non-splenectomized patients. Enzyme
      infusion therapy can be recommended in type 3 Gaucher disease.

PMID- 8544960
TI  - Cerebellar involvement in hypomelanosis of Ito.
AB  - Hypomelanosis of Ito (HI) (incontinentia pigmenti achromians) with cerebellar
      atrophy and dysmorphic features is reported in a child. The association of
      cerebellar anomalies and HI has been previously reported in only four cases.
      However, since neuroimaging studies are not routinely obtained in these patients
      the frequency of this association might have been underestimated. In cases of
      otherwise unexplained cerebellar ataxia an examination of the skin with Wood's
      lamp should be performed since the typical hypopigmented lesions can be hardly
      visible in natural light.

PMID- 8544961
TI  - The effect of behavioural states on visual evoked responses in preterm and full
      term newborns.
AB  - There is no general agreement about the influence of the behavioural states on
      the visual evoked responses. In the present study visual evoked potentials (VEP)
      were recorded in 6 preterm and 6 full-term newborns in the different behavioural
      states. A significant increase in the amplitude was observed from sleep to awake
      states in both preterm and full-term infants. The results supply information in
      favour of the utility of the behavioural assessment when VEP are recorded. It
      reduces the variability of the results providing for more reliable normative
      data.

PMID- 8544962
TI  - Dystonic posture of lower extremities associated with myelomeningocele:
      successful treatment with botulinum A toxin in a six-month-old child.
AB  - We report on a six-month-old child with severe intermittent dystonic posture of
      both legs associated to a thoraco-lumbar myelomeningocele. The patient presented
      with a combination of progressive hypertonic knee extension and hip flexion.
      While the mobility of the right leg improved sufficiently after physiotherapy and
      splinting, satisfactory improvement of the left leg could be achieved only after
      local injections of botulinum A toxin, allowing for adequate functional motor
      development.

PMID- 8544963
TI  - Intrafamilial phenotypic heterogeneity of the Poland complex: a case report.
AB  - Three cases of familial unilateral gluteal hypoplasia are reported. The index
      case in addition to having gluteal hypoplasia also has unilateral pectoral muscle
      hypoplasia. Another relative has unilateral symbrachydactyly of the distal
      phalanges of one foot. All four affected individuals in our pedigree were female.
      We propose that our cases are best classified as part of the Poland complex of
      anomalies. Our cases emphasize that intrafamilial phenotypic heterogeneity is
      possible within the Poland complex.

PMID- 8544964
TI  - Sturge-Weber syndrome without facial nevus.
AB  - A patient with Sturge-Weber syndrome without the characteristic facial nevus
      presented with focal seizures which were difficult to control and borderline
      mental level. CT disclosed calcification in the right occipital zone. A marked
      decrease of the regional cerebral blood flow that extended beyond the
      abnormalities depicted on CT was seen by SPECT. Venous magnetic resonance (MR)
      angiography revealed reduction of the superficial cortical veins and prominent
      deep collateral venous system in the same side of the cerebral lesion. Cranial MR
      imaging with Gd-DTPA demonstrated the pial angioma.

PMID- 8544965
TI  - Prolonged epileptic apneas in a newborn: a case report with ictal EEG recording.
AB  - We report a case of repetitive and prolonged apneas, correlating with EEG-focal
      epileptiform discharges over the right temporal region, in a full-term newborn.
      After administration of phenobarbital the apneas completely ceased. The
      neurological examination, the psychomotor development, and the EEG at the age of
      12 months were normal. The prolonged duration of the epileptic apneas, the ictal
      rhythmic delta wave activity, and the favorable outcome distinguish our patient
      from the majority of previously reported cases.

PMID- 8544966
TI  - Tardive psychopathology.
AB  - Tardive psychopathology (TP) corresponds to mental changes from chronic
      neuroleptic exposure, as tardive dyskinesia corresponds to induced movement
      disorders. TP was prospectively identified in 4 inpatients. Each took
      neuroleptics more than 3 years, showed good premorbid adjustment or initiative,
      and met criteria for chronic schizophrenia. Each also had obsessions or
      compulsions, and apathetic dysphoria, symptoms not previously attributed to TP.
      Following neuroleptic termination with introduction of lithium and sertraline,
      each showed atypically rapid disappearance of this psychopathology. The incidence
      of these features is over 47% (p < 0.05). Some cases of apparent neuroleptic
      resistant schizophrenia may be TP.

PMID- 8544967
TI  - Increased frequency of the extended or ancestral haplotype B44-SC30-DR4 in
      autism.
AB  - Autism likely results from several different etiologies or a combination of
      pathological mechanisms. Recent studies suggest that this disorder may be
      associated with immune abnormalities, pathogen-autoimmune processes and perhaps
      the major histocompatibility complex (MHC). In a preliminary study we found that
      22 autistic subjects had an increased frequency of the extended or ancestral MHC
      haplotype B44-SC30-DR4. The current study attempted to confirm this observation
      by studying 23 additional randomly chosen autistic subjects, most of their
      parents and 64 unrelated normal subjects. In agreement with earlier findings B44
      SC30-DR4 was associated with autism. In combining the data from the original and
      current studies, B44-SC30-DR4 or a substantial fragment of this extended
      haplotype was represented in 40% of the autistic subjects and/or their mothers as
      compared to about 2% of the unrelated subjects. It is concluded that one or more
      genes of the MHC is (are) involved in the development of some cases of autism.

PMID- 8544968
TI  - Effect of acute treatment with sodium valproate on catecholamine and serotonin
      synthesis in mouse cerebral cortex.
AB  - We examined the effect of sodium valproate (VPA) on monoamine synthesis in the
      mouse cerebral cortex by measuring the accumulation of L-3,4
      dihydroxyphenylalanine and 5-hydroxytryptophan following inhibition of aromatic L
      amino acid decarboxylase. Treatment with VPA decreased catecholamine synthesis,
      in a dose-dependent manner, with maximum inhibition 60 min following treatment.
      Muscimol, a GABAA receptor agonist, also decreased catecholamine synthesis,
      although baclofen, a GABAB receptor agonist, did not. Picrotoxin, a GABAA
      receptor antagonist, inhibited the VPA-induced decrease in catecholamine
      synthesis. However, serotonin synthesis was not significantly changed by VPA.
      These results suggest that acute treatment with VPA reduces the synthesis of
      catecholamines via GABAA receptors.

PMID- 8544969
TI  - EEG sleep characteristics in dysthymia and major depressive disorder.
AB  - All night EEG sleep recordings were compared in patients with dysthymia and major
      depressive disorder. Subjects were selected according to DSM-IV and underwent 2
      weeks of treatment with placebo before the sleep evaluations. All patients with
      major depressive disorder were classified as nonmelancholic and belonged to the
      recurrent subtype, without full interepisode recovery. Patients with major
      depressive disorder have a shorter duration of total sleep time, a longer sleep
      latency and a lower sleep efficiency. However, similar sleep architecture and REM
      sleep characteristics were found in the two groups. These EEG sleep data seem to
      favor the existence of a biological overlap between the two forms of
      nonmelancholic unipolar depression. The validity of dysthymia is still unclear
      and therefore the nosological implications of our observations are discussed.

PMID- 8544970
TI  - Serum levels of carnitine in chronic fatigue syndrome: clinical correlates.
AB  - Carnitine is essential for mitochondrial energy production. Disturbance in
      mitochondrial function may contribute to or cause the fatigue seen in chronic
      fatigue syndrome (CFS) patients. One previous investigation has reported
      decreased acylcarnitine levels in 38 CFS patients. We investigated 35 CFS
      patients (27 females and 8 males); our results indicate that CFS patients have
      statistically significantly lower serum total carnitine, free carnitine and
      acylcarnitine levels, not only lower acylcarnitine levels as previously reported.
      We also found a statistically significant correlation between serum levels of
      total and free carnitine and clinical symptomatology. Higher serum carnitine
      levels correlated with better functional capacity. These findings may be
      indicative of mitochondrial dysfunction, which may contribute to or cause
      symptoms of fatigue in CFS patients.

PMID- 8544971
TI  - Cerebral perfusion, electrical activity and effects of serotonergic treatment in
      obsessive-compulsive disorder. A preliminary study.
AB  - An abnormally increased glucose metabolism has been described with positron
      emission tomography (PET) in frontal and caudate regions of obsessive-compulsive
      patients. Perfusion and electroencephalographic studies have been less
      conclusive. However, these techniques are, currently, more available than PET
      and, therefore, deserve further study because of their possible clinical
      applications. In this article, 13 obsessive-compulsive patients were studied with
      quantitative EEG and auditory and visual evoked potentials. Six of them were
      studied also with perfusion single photon emission tomography. A group of 4
      patients was studied with both techniques before and after a serotonergic
      treatment. Increased global, beta, and theta electrical power together with an
      increased perfusion in frontal regions was observed. The patients also showed a
      delta power increase over right temporal and frontal regions, together with
      increased perfusion in the right basal ganglia region as well as a decreased
      amplitude of the P50 and N100 waves of the auditory evoked potentials over
      temporal electrodes; these alterations were reduced with treatment. These results
      are discussed in the context of current data about serotonergic
      neurotransmission.

PMID- 8544972
TI  - Dose-dependent effects of chronic amphetamine administration in local cerebral
      glucose utilization in rat.
AB  - The daily dose of amphetamine pretreatment may affect the development of
      behavioral-sensitized patterns in rodents and amphetamine psychosis in humans.
      This experiment investigated the regional cerebral metabolic changes in rats
      after pretreatment with different doses of amphetamine by the 2-[14C]deoxyglucose
      method. Rates of local cerebral glucose utilization were examined in 37 regions
      of the rat brain. The result showed generally maximal metabolic augmentation in
      the 5.0 mg/kg group instead of in the 1.0 or the 10.0 mg/kg groups. Behavioral
      testing using motor activity cages in rats with the same regimen found no
      difference among groups. The findings demonstrate that there might be a window
      effect by daily amphetamine dose on the development of drug dependence and
      amphetamine psychosis. It was suggested that the 2(-)[14C]deoxyglucose method
      could be used for further study of animal models of amphetamine psychosis.

PMID- 8544973
TI  - Effects of diazepam and buspirone on reaction time of saccadic eye movements.
AB  - Effects of the anxiolytic drugs diazepam and buspirone were studied on the
      reaction time of saccadic eye movements. The study was performed with 8 healthy
      volunteers in a double-blind, placebo-controlled way. The purpose was to
      investigate the putative drug effects on the first step of an attention shifting
      task: the disengagement of attention. Saccadic reaction time was measured in two
      conditions: the 'gap' and the 'overlap' condition. In the first condition a delay
      is present between the offset of a fixation spot and the onset of a target, while
      in the second condition the offset of the spot is overlapped by the onset of the
      target. Clear differences in saccadic reaction time in the expected direction
      were found between the two conditions, with longer reaction times of saccadic eye
      movements in the overlap condition. The nonsedative anxiolytic buspirone in a
      dose of 5 mg had no significant effects on saccadic reaction times, while clear
      effects of diazepam in a dose of 5 mg were established. Diazepam slowed down
      saccadic reaction times, reduced the number of fast saccades and facilitated the
      number of slow saccades. However, the effects induced by this drug were identical
      for the two conditions. The latter result implies that the disengagement of
      attention is not selectively disrupted by diazepam. Perhaps, the action of
      diazepam is expressed in other attention factors, such as in shifting attention
      or in the reengagement of attention. A slowing down of these processes by the
      vigilance-lowering properties of diazepam might be the cause of the prolonged
      latencies. The increased latencies of saccadic eye movements induced by a low
      dose of diazepam may have practical implications.

PMID- 8544974
TI  - Effects of cigarette smoking on performance in a simulated driving task.
AB  - A double-blind study was conducted to investigate the psychomotor effects of
      cigarette smoking on a 1-hour computer-based simulation of driving comprising
      continuous tracking and brake reaction time tasks. Twelve minimally abstinent
      smoker subjects were asked to operate the simulator on four occasions while
      smoking single cigarettes yielding varying levels of nicotine (< 0.1, 0.6, 1.0 or
      2.1 mg) but similar levels (8-10 mg) of tar. Data were transformed with regard to
      baseline scores to counter day-to-day differences in performance and showed brake
      reaction times to be improved after all active treatments (p < 0.01) but tracking
      accuracy to be enhanced after the two cigarettes of middle strength alone (p <
      0.05). These results suggest that, among smokers cigarette smoking may improve
      driving performance and that there may exist an optimal nicotine dose for the
      enhancement of cognitive and psychomotor function.

PMID- 8544975
TI  - Standard operating procedure for the registration and computer-supported
      evaluation of pharmaco-EEG data. 'EEG in Phase I' of the Collegium Internationale
      Psychiatriae Scalarum (CIPS).
AB  - The working team 'EEG in Phase I' of the Collegium Internationale Psychiatriae
      Scalarum presents a standard operating procedure (SOP) for the registration and
      computer-supported evaluation of pharmaco-EEG data, which is based on published
      guidelines. The minimum standard for recording, amplifying and filtering,
      validation of hardware and software, artifact treatment and fast Fourier analysis
      is described in a tabulated from and further explained as accompanying comments.
      The available SOP can be the basis for the working out of laboratory-specific
      SOPs. Compliance with the SOP guarantees the possibility of citation by the
      International Pharmaco-EEG Group (IPEG), Association for Methodology and
      Documentation in Psychiatry (AMDP), and Collegium Internationale Psychiatriae
      Scalarum (CIPS). Furthermore, an optimal standard is recommended where
      appropriate, which functions as a guideline.

PMID- 8544976
TI  - Smaller auditory P300 amplitude in schizophrenics in remission.
AB  - The P300 event-related potential (ERP) was recorded using the auditory oddball
      paradigm in 12 (6 male) schizophrenic (DSM-IIIR) patients in rigorously defined
      clinical remission. The ERP was also recorded in 10 (5 male) age-, sex- and
      education-matched control subjects. ERP latencies and amplitude were measured at
      Cz and Pz recording sites. Mean latencies of the P300 in schizophrenic patients
      in remission at Cz [343.6 +/- 31 (SD) ms] and Pz (346.15 +/- 30 ms) did not
      differ from those of normals (Cz: 332.8 +/- 23 ms, Pz: 323 +/- 38 ms). The P300
      ERP amplitude was significantly (p < 0.05) smaller in schizophrenics in remission
      at both Cz (9.2 +/- 4.4 microV) and Pz (8.8 +/- 4.4 microV) than in normals (Cz:
      13.3 +/- 2.90 microV; Pz: 12.71 +/- 4.18 microV). The significance of the smaller
      auditory P300 amplitude in schizophrenia is discussed.

PMID- 8544977
TI  - Alterations of Ca2+/calmodulin-dependent protein kinase II and its messenger RNA
      in the rat hippocampus following normo- and hypothermic ischemia.
AB  - The change in the subcellular distribution of Ca2+/calmodulin-dependent protein
      kinase II was studied in the rat hippocampus following normothermic and
      hypothermic transient cerebral ischemia of 15 min duration. A decrease in
      immunostaining of Ca2+/calmodulin-dependent protein kinase II was observed at 1 h
      of reperfusion which persisted until cell death in the CA1 region. In the CA3 and
      dentate gyrus areas immunostaining recovered at one to three days of reperfusion.
      The CA2+/calmodulin-dependent protein kinase II was translocated to synaptic
      junctions during ischemia and reperfusion which could be due to a persistent
      change in the intracellular calcium ion homeostasis. The expression of the
      messenger RNA of the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II
      decreased in the entire hippocampus during reperfusion, and was most marked in
      the dentate gyrus at 12 h of reperfusion. This decrease could be a feedback
      downregulation of the mRNA due to increased Ca2+/calmodulin-dependent protein
      kinase II activation. Intraischemic hypothermia protected against ischemic
      neuronal damage and attenuated the ischemia-induced decrease of Ca2+/calmodulin
      dependent protein kinase II immunostaining in all hippocampal regions.
      Hypothermia also reduced the translocation of Ca2+/calmodulin-dependent protein
      kinase II and restored Ca2+/calmodulin-dependent protein kinase II alpha
      messenger RNA after ischemia. The data suggest that ischemia leads to an aberrant
      Ca2+/calmodulin-dependent protein kinase II mediated signal transduction in the
      CA1 region, which is important for the development of delayed neuronal damage.
      Hypothermia enhances the restoration of the Ca2+/calmodulin-dependent protein
      kinase II mediated cell signalling.

PMID- 8544979
TI  - Pyramidal neurons with ectopic dendrites in storage diseases exhibit increased
      GM2 ganglioside immunoreactivity.
AB  - Cortical pyramidal neurons in several types of neuronal storage diseases have
      been shown by Golgi staining to sprout axon hillock-associated dendritic
      processes. Based on the relative incidence of this ectopic dendritogenesis, and
      on quantitative analyses of gangliosides in these same tissues, it has been
      proposed that abnormal accumulation of a specific metabolic product, GM2
      ganglioside, is the pivotal event leading to re-initiation of dendritic sprouting
      [Siegel D. A. Walkley S.U. (1994) J. Neurochem. 62, 1852-1862]. In the present
      study, a monoclonal antibody was used to determine the cellular location of this
      ganglioside within the cerebral cortex of animal models of storage diseases with
      and without ectopic dendrite growth. Diseases exhibiting ectopic dendritogenesis
      included inherited and swainsonine-induced (juvenile-onset) alpha-mannosidosis,
      mucopolysaccharidosis type I, Niemann-Pick disease type C, and GM1 and GM2
      gangliosidosis. Conditions lacking ectopic dendrite growth included adult-onset
      swainsonine-induced alpha-mannosidosis, fucosidosis, neuronal ceroid
      lipofuscinosis (Batten disease) and normal, mature brain. Immunocytochemical
      staining for GM2 ganglioside indicated that diseases exhibiting new dendritic
      sprouting with the exception of GM1 gangliosidosis, exhibited abundant GM2-like
      immunoreactivity within the cortical pyramidal cell population, whereas diseases
      without dendritic sprouting had GM2-like immunoreactivity limited to glia and/or
      to non-pyramidal neurons. Cortical tissues from normal animals at comparable ages
      and processed by similar procedures exhibited occasional glial cell staining but
      little or no neuronal labelling. Mechanisms by which normal cortical pyramidal
      regulate dendritic initiation are poorly understood. However, it is known that
      this event is developmentally restricted, occurring only during early brain
      development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544978
TI  - Synergistic activation by cis-fatty acid and diacylglycerol of protein kinase C
      and protein phosphorylation in hippocampal slices.
AB  - cis-Unsaturated fatty acid, which activates protein kinase C in vitro, stimulates
      protein phosphorylation in intact hippocampal slices. Two protein bands (44,000
      and 47,000 mol. wt) are particularly sensitive to cis-fatty acid and are
      phosphorylated in a dose- and time-dependent manner. The cis-fatty acid
      stimulated protein phosphorylation can be further potentiated with diacylglycerol
      or 12-O-tetradecanoylphorbol 13-acetate. Several lines of evidence indicate that
      the cis-fatty acid-stimulated phosphorylation of these proteins is mediated by
      protein kinase C. First, the cis-fatty acid effect is mimicked by other protein
      kinase C activators such as diacylglycerol. Second, the stimulation of the
      phosphorylation by these activators can be blocked by staurosporine, which
      potently inhibits protein kinase C. Third, a concomitant application of cis-fatty
      acid and diacylglycerol or 12-O-tetradecanoylphorbol 13-acetate enhances the
      44,000 and 47,000 mol. wt phosphorylation in a synergistic manner, which is a
      novel activation mode for protein kinase C. Fourth, they can be phosphorylated by
      purified protein kinase C (type III: alpha). Moreover, the synergistic activation
      of purified protein kinase C by cis-fatty acid and diacylglycerol leads to a
      drastic increase in the phosphorylation of these two protein bands. Two
      dimensional gel electrophoresis and immunoblot analysis revealed that they are
      both acidic proteins. The 47,000 mol. wt band consists of two protein components;
      one is found to be F1/growth-associated protein-43 (pI = 4.5), and the other
      47,000 mol, wt protein has broad pI ranging from 4.6 to 4.9. The 44,000 mol. wt
      component is a major phosphoprotein with pI of 4.8-5.1. Our results strongly
      indicate that cis-fatty acid can act as a regulator of endogenous protein kinase
      C in concert with diacylglycerol, and stimulate protein phosphorylation of its
      substrates such as F1/growth-associated protein-43 in the hippocampus.

PMID- 8544980
TI  - Neurochemical changes following occlusion of the middle cerebral artery in rats.
AB  - We have developed a stroke model involving middle cerebral artery occlusion in
      the rat which elicits changes in cardiac and autonomic variables that are similar
      to those observed clinically. It is likely that these neurogenic autonomic
      responses are mediated by changes in neurotransmitter systems subsequent to the
      stroke. This possibility was investigated by examining changes in
      immunohistochemical staining for tyrosine hydroxylase, neuropeptide Y, leu
      enkephalin, neurotoxins and dynorphin following middle cerebral artery occlusion
      in the rat. Computerized image analysis was used to provide semi-quantitative
      measurements of the changes. The ischemic region was centered primarily in the
      insular cortex. The results indicate that there are significant increases in
      immunostaining for tyrosine hydroxylase and neuropeptide Y in the insular cortex
      within the peri-infarct region. Neuropeptide Y staining was also significantly
      increased in the basolateral nucleus of the amygdala, ipsilateral to the middle
      cerebral artery occlusion, which did not appear to be included in the infarct.
      Leu-enkephalin, neurotensin and dynorphin staining was significantly elevated in
      the central nucleus of the amygdala ipsilateral to the occlusion of the middle
      cerebral artery. These neurochemical changes are discussed as possible mechanisms
      mediating the cardiac and autonomic consequences of stroke or as part of a
      process to provide neuro-protection following focal cerebral ischemia.

PMID- 8544981
TI  - The calcium response to the excitotoxin kainate is amplified by subsequent
      reduction of extracellular sodium.
AB  - The relation between intracellular and extracellular [Na+] and [Ca2+] and
      membrane potential during stimulation of non-N-methyl-D-aspartate glutamate
      receptors has been studied in cerebellar granule cells using the fluorescent
      indicators SBFI, fura-2 and the bisoxonol membrane potential probe DiBaC4(3).
      Kainate increased both [Ca2+]i (intracellular [Ca2+]) and [Na+]i (intracellular
      [Na+]) and depolarized the membrane. This elevation of [Ca2+]i was only partially
      dependent on the presence of extracellular Na+ at the time of kainate addition.
      Removal of extracellular Na+ itself had a very minor effect on the [Ca2+]i or
      membrane potential of unstimulated cells. If extracellular Na+ was removed (in
      order to reverse the [Na+] gradient) or its concentration reduced during
      stimulation with kainate, the membrane depolarization recovered as expected.
      However, the intracellular level of sodium recovered only very slowly and the
      [Ca2+]i rose sharply, rather than recovering as might be expected on
      repolarization of depolarized cells possessing voltage sensitive calcium
      channels. This effect of extracellular [Na+] reduction on [Ca2+]i was mimicked by
      ouabain, another agent that causes accumulation of [Na+] in cells. These results
      suggest that Na+/Ca2+ exchange may play a major role in calcium homeostasis in
      stimulated cells, and that the levels of Na+ inside and outside the cell are
      critical in determining the effect of receptor stimulation on the intracellular
      [Ca2+].

PMID- 8544982
TI  - Modelling the role of the cerebellar fastigial nuclei in producing accurate
      saccades: the importance of burst timing.
AB  - Clinical and experimental data indicate that damage to the cerebellar vermis
      results in permanent loss of saccadic accuracy. Models of saccade production
      therefore need to provide a role for the cerebellum. It has been proposed that
      the vermis adjusts the gain of the saccadic internal feedback loop in response to
      information about the amplitude of the intended saccade. A model of how the
      fastigial nuclei (through which vermal output is channelled) influence brainstem
      saccadic circuitry to achieve this effect was constructed in three stages. (1)
      The brainstem was represented by a version of Robinson's internal feedback model,
      which relates excitatory burst neuron discharge to horizontal saccade dynamics.
      (2) The original model was lesioned to simulate the effects of bilateral
      inactivation of the fastigial nuclei, namely slow hypermetric saccades. This
      required reducing the synaptic weight of the internal feedback pathway, and
      lowering the gain of the excitatory burst neurons. The resultant brainstem-only
      model served as a preparation for testing the effects of neuronal discharge
      patterns within the fastigial nuclei. (3) These discharge patterns were simulated
      using measurements from recent electrophysiological studies. It was found that
      saccadic accuracy and normal dynamics were restored in the model if the simulated
      burst from neurons in the contralateral fastigial nucleus were subtracted from
      the feedback signal (i.e. added to the command signal) early in the saccade, and
      the burst from neurons in the ipsilateral fastigial nucleus were added to the
      feedback signal later in the saccade. This pattern corresponds to the observed
      timing of neuronal bursts in the fastigial nuclei, and accounts qualitatively for
      the effects of unilateral stimulation and inactivation of both the fastigial
      nuclei and the cerebellar vermis. This method of producing accurate saccades also
      contributes to time optimal control, by increasing both saccadic acceleration and
      deceleration. Appropriate timing of burst onset and duration in the fastigial
      nuclei is essential for these roles. Evidence concerning the effects of
      cerebellar damage on fast movements of other parts of the body suggests that the
      cerebellum may use similar strategies for controlling a wide range of simple
      movements.

PMID- 8544983
TI  - Release of cerebral 5-hydroxytryptamine evoked by electrical stimulation of the
      dorsal and median raphe nuclei: effect of a neurotoxic amphetamine.
AB  - Recent neuroanatomical data suggest that the axons and terminals of serotonergic
      neurons of the dorsal and median raphe nuclei are morphologically and
      pharmacologically distinct. Here we attempted to establish a functional in vivo
      model of serotonergic terminals derived from these nuclei, and then carry out a
      preliminary comparison of their physiological and pharmacological properties.
      Brain microdialysis was used to monitor extracellular 5-hydroxytryptamine in the
      hippocampus (dorsal and median raphe innervation) and frontal cortex
      (preferential dorsal raphe innervation) of the anaesthetized rat. To distinguish
      5-hydroxytryptamine released by terminals of dorsal raphe neurons from that
      released by median raphe neurons, one or other of these nuclei was stimulated
      electrically. Electrical stimulation of either the dorsal or median raphe nucleus
      evoked a release of 5-hydroxytryptamine in the hippocampus. Whereas stimulation
      of the dorsal raphe nucleus also released 5-hydroxytryptamine in the frontal
      cortex, stimulation of the median raphe nucleus did not. No release of 5
      hydroxytryptamine was evoked when electrodes were located in regions bordering
      the dorsal raphe nucleus and the median raphe nucleus. The amounts of hippocampal
      5-HT released by stimulation of the dorsal or median raphe nucleus were found to
      be similarly altered by a 5-hydroxytryptamine uptake inhibitor (citalopram) and
      calcium-free perfusion medium, and also by increasing stimulation frequency (2-10
      Hz). Furthermore, the amount of 5-hydroxytryptamine released by electrical
      stimulation of either the dorsal raphe nucleus or median raphe nucleus was
      markedly reduced in rats pretreated with p-chloroamphetamine. In summary, our
      data show that electrical stimulation of the dorsal or median raphe nucleus
      releases 5-hydroxytryptamine in a regionally specific manner (hippocampus versus
      frontal cortex), suggesting that serotonergic nerve terminals of the dorsal and
      median raphe pathways were being activated selectively. Using this model, we
      found no differences in the responsiveness of dorsal and median raphe pathways to
      a specific set of physiological and pharmacological manipulations. In particular,
      our data suggest that the neurotoxic action of p-chloroamphetamine may not be
      targeted solely on serotonergic axons and terminals of the dorsal raphe nucleus
      but includes those of the median raphe nucleus.

PMID- 8544984
TI  - Induction of c-fos in rat forebrain by pharmacological manipulation of 5
      hydroxytryptamine levels.
AB  - The immunocytochemical localization of the immediate-early gene c-fos has been
      used to map sites of neuronal activity in the rat brain associated with 5
      hydroxytryptamine function. Behavioural studies have shown that brain 5
      hydroxytryptamine function is increased by treatment of animals with a
      combination of the 5-hydroxytryptamine precursor L-tryptophan (100 mg/kg) and the
      monoamine inhibitor tranylcypromine (20 mg/kg). We now report that such treatment
      induces a specific anatomical pattern of expression of c-fos in rat forebrain in
      many limbic, striatal and cortical areas which corresponds well with the
      distribution of 5-hydroxytryptamine-immunoreactive terminals. To investigate
      further the involvement of 5-hydroxytryptamine in this response, we pretreated
      animals with the tryptophan hydroxylase inhibitor p-chlorophenylalanine and
      observed the effects on Fos-like immunoreactivity after L-tryptophan and
      tranylcypromine challenge. Two-day pretreatment with p-chlorophenylalanine (300
      mg/kg) prior to tranylcypromine and L-tryptophan resulted in a significant
      attenuation of Fos-like immunoreactivity in specific brain areas, including the
      piriform and frontal cortices, nucleus accumbens, caudate-putamen,
      paraventricular hypothalamus and paraventricular thalamic nucleus. A marked
      reduction of the hyperactivity syndrome was also seen, as has been reported in
      earlier studies. The results of this study suggest that the elevation in Fos-like
      immunoreactivity following treatment with tryptophan and a monoamine oxidase
      inhibitor is mainly due to increased 5-hydroxytryptamine synthesis and release.
      It is well known that 5-hydroxytryptamine mediates mood and affect, and this
      study indicates potential brain loci of action of serotonergic drugs.

PMID- 8544985
TI  - Impairment of blood-brain barrier function by serotonin induces desynchronization
      of spontaneous cerebral cortical activity: experimental observations in the
      anaesthetized rat.
AB  - The possibility that elevation of serotonin in the circulation, which is found in
      various pathological states, influences the spontaneous cerebral cortical
      activity was examined in a rat model. The electroencephalogram was recorded using
      bipolar epidural electrodes placed over the frontal and parietal cerebral cortex.
      Intravenous infusion of serotonin (10 micrograms/kg per min for 10 min) decreased
      the electroencephalogram amplitude in both frontal and parietal recordings within
      4 min of infusion. This decrease in amplitude was reversible, Pretreatment with
      cyproheptadine (a potent serotonin2 receptor antagonist) prevented the serotonin
      induced decrease of the electroencephalogram amplitude. The blood-brain barrier
      permeability to Evans Blue and [131I]sodium was increased in frontal and parietal
      cortex. This increase in blood-brain barrier permeability was absent in animals
      pretreated with cyproheptadine. These results provide direct evidence that an
      elevated level of serotonin in blood has the capacity to influence spontaneous
      cortical electrical activity. This effect of serotonin on electroencephalogram
      appears to be due to its ability to enter into the brain parenchyma by inducing a
      short-term breakdown of the blood-brain barrier, probably via serotonin2
      receptors.

PMID- 8544986
TI  - Electrophysiological and pharmacological properties of interneurons in the cat
      dorsal lateral geniculate nucleus.
AB  - We investigated the electrophysiological and pharmacological properties of
      morphologically identified and putative interneurons within laminae A and A1 of
      the cat dorsal lateral geniculate nucleus maintained in vitro. These intralaminar
      interneurons possess unique electrophysiological characteristics, including (1)
      action potentials of a short duration (average width at half amplitude of 0.34
      ms). (2) the ability to generate high-frequency trains of action potentials
      exceeding 500 Hz, without strong spike frequency adaptation, and (3) a low
      threshold regenerative response with variable magnitude of expression, ranging
      from a subthreshold depolarization towards the generation of one to several
      action potentials in different cells. The low-threshold regenerative
      depolarization following a hyperpolarizing current pulse was increased in size by
      application of 4-aminopyridine, was reduced by nickel, and was not influenced by
      extracellular cesium. These findings indicate that this event is mediated by an
      underlying Ca(2+)-dependent mechanism, such as a low-threshold Ca(2+) current,
      that is regulated by the activation of opposing transient K+ currents. Every
      interneuron tested responded to glutamate, kainate, quisqualate, or N-methyl-D
      aspartate with depolarization and action potential discharge. In contrast, we did
      not observe a postsynaptic response to activation of the metabotropic receptors
      with 1S,3R-(+/-)-1-amino-cyclopentane-1,3-dicarboxylate. Application of gamma
      amino-butyric acid (GABA) strongly inhibited spike firing through a biphasic
      hyperpolarization and increase in membrane conductance, a response that reversed
      close to the presumed chloride equilibrium potential and was imitated by the
      GABAA receptor agonist muscimol. The GABAB receptor agonist baclofen evoked only
      a weak membrane hyperpolarization from rest and suppression of spontaneous spike
      activity. Application of acetylcholine, or the muscarinic agonist acetyl-beta
      methylcholine, inhibited spontaneous action potential activity through
      hyperpolarization of the membrane potential, presumably resulting from an
      increase in membrane potassium conductance. In contrast, application of serotonin
      only slightly facilitated tonic activity in a subpopulation of interneurons,
      histamine induced a small slow depolarization apparently through activation of
      presynaptic excitatory pathways, and noradrenaline and adenosine had no
      detectable effect on the spontaneous firing or resting potential of interneurons.
      We suggest that intralaminar interneurons may function in a relatively linear
      manner to transform retinal and cortical inputs into a local field of inhibition
      in the dorsal lateral geniculate and that the excitability of these neurons is
      largely controlled by retinal, cortical, GABAergic, and cholinergic (brainstem)
      afferents.

PMID- 8544987
TI  - Pharmacological characterization of pre- and postsynaptic GABAB receptors in the
      deep nuclei of rat cerebellar slices.
AB  - Whole-cell current-and voltage-clamp recordings were made from deep nuclear
      neurons in cerebellar slices from seven- to nine-day-old rats. Baclofen, a GABAB
      agonist, produced a slow postsynaptic hyperpolarization associated with a
      decrease in input resistance. The hyperpolarization was G-protein-dependent,
      blocked by intracellular Cs+ and antagonized by CGP 35348, a GABAB antagonist. In
      dialysed neurons recorded with Cs+ -containing pipettes, baclofen suppressed deep
      nuclear neuronal inhibitory postsynaptic potentials and inhibitory postsynaptic
      currents evoked by electrical stimulations of the Purkinje cell axons. This
      effect was blocked by CGP 35348, indicating that the suppressions were mediated
      by presynaptic GABAB receptors. The inability of CGP 35348 or uptake inhibitors
      (nipecotic acid and NO-711) to alter the decay of inhibitory postsynaptic
      currents evoked by maximal stimulation suggested that GABAB receptors are not
      activated by the stimulation of the GABAergic input. Paired-pulse depression of
      inhibitory postsynaptic currents was not blocked by CGP 35348. Moreover, neither
      uptake inhibitors nor CGP 35348 produced any significant changes to the whole
      cell current produced by a tetanic stimulation of Purkinje cell axons, suggesting
      that GABAB autoreceptors were also not activated by endogenous GABA release. Our
      findings indicate that while pre- and postsynaptic GABAB receptors are present in
      the deep nuclei of the rat cerebellum, they are not activated by electrical
      stimulation of the Purkinje cell axons.

PMID- 8544988
TI  - Norepinephrine modulates high voltage-activated calcium channels in freshly
      dissociated rat nucleus tractus solitarii neurons.
AB  - The effects of norepinephrine on the low- and high-voltage-activated calcium
      channels in the neurons acutely dissociated from the nucleus tractus solitarius
      of 2- to 3-week-old rats were investigated in the nystatin perforated patch
      recording configuration under voltage-clamp conditions. The norepinephrine had no
      effect on the low voltage-activated calcium channel but inhibited the high
      voltage-activated calcium channel in a concentration-, time- and voltage
      dependent manner. The norepinephrine slowed the activation phase of the high
      voltage-activated calcium channel current and the maximum inhibition was 30% of
      the total current amplitude measured 10 ms after the current activation. The
      inhibitory effect was eliminated by applying larger depolarizing prepulses. The
      pretreatment with pertussis toxin completely blocked the norepinephrine effect on
      high-voltage activated calcium channels, suggesting the contribution of pertussis
      toxin-sensitive Gi/Go-proteins to the norepinephrine-induced inhibition.
      Yohimbine but not prazosin nor propranolol antagonized the norepinephrine-induced
      inhibition, suggesting the involvement of alpha 2-adrenoceptor in norepinephrine
      induced inhibition of the high voltage-activated calcium channels. omega
      Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine and omega-conotoxin-MVIIC blocked
      the high voltage-activated calcium channel current by 26, 9, 36 and 11% of the
      total current respectively, suggesting the existence of N-, P-, L- and Q-type
      calcium channels in the nucleus tractus solitarii neurons. The current being
      insensitive to these calcium channel antagonists, termed R-type calcium channel
      current, also existed. This residual R-type calcium channel was completely
      blocked by adding 200 microM CD2+. The norepinephrine significantly inhibited N-
      and P-type calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544989
TI  - Cationic influences upon synaptic transmission at the hair cell-afferent fiber
      synapse of the frog.
AB  - The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated
      frog labyrinth were varied in order to assess their role in influencing and
      mediating synaptic transmission at the hair cell-afferent fiber synapse.
      Experiments employed intracellular recordings of synaptic activity from VIIIth
      nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory
      postsynaptic potentials were detected and parameters quantified by computer
      algorithms. Particular attention was focused on cationic effects upon excitatory
      postsynaptic potential frequency of occurrence and excitatory postsynaptic
      potential amplitude, in order to discriminate between pre- and postsynaptic
      actions. Because the small size of afferents preclude long term stable
      recordings, alterations in cationic concentrations were applied transiently and
      their peak effects on synaptic activity were assessed. Increases in extracellular
      K+ concentration of a few millimolar produced a large increase in the frequency
      of occurrence of excitatory postsynaptic potentials with little change in
      amplitude, indicating that release of transmitter from the hair cell is tightly
      coupled to its membrane potential. Increasing extracellular Na+ concentration
      resulted in an increase in excitatory postsynaptic potential amplitude with no
      significant change in excitatory postsynaptic potential frequency of occurrence,
      suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions.
      Decreases in extracellular Ca2+ concentration had little effect upon excitatory
      postsynaptic potential frequency, but increased excitatory postsynaptic potential
      frequency and amplitude. These findings suggest that at higher concentrations
      Ca2+ act presynaptically to prevent transmitter release and postsynaptically to
      prevent Na+ influx during the generation of the excitatory postsynaptic
      potential. The influences of these ions on synaptic activity at this synapse are
      remarkably similar to those reported at the vertebrate neuromuscular junction.
      The major differences between these two synapses are the neurotransmitters and
      the higher resting release rate and higher sensitivity of release to increased K+
      concentrations of the hair cells over that of motor nerve terminals. These
      differences reflect the functional roles of the two synapses: the motor nerve
      terminal response in an all-or-nothing signal consequent from action potential
      invasion, while the hair cell releases transmitter in a graded fashion,
      proportionate to the extent of stereocilial deflection. Despite these differences
      between the two junctions, the similar actions of these elemental cations upon
      synaptic function at each implies that these ions may participate similarly in
      the operations of other synapses, independent of the neurotransmitter
      type.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8544990
TI  - The telencephalic vesicles are innervated by olfactory placode-derived cells: a
      possible mechanism to induce neocortical development.
AB  - During early embryonic development, the olfactory placode is the source of
      different cell types migrating toward the telencephalic vesicle. Among these cell
      types are the ensheathing cells, the luteinizing hormone-releasing hormone
      producing cells and the olfactory marker protein-immunoreactive cells. We have
      identified a novel group of olfactory placode-derived migratory cells using an
      antibody against beta-tubulin to label neurons and acetylcholinesterase
      histochemistry to label posmitotic cells. In this paper we describe the
      morphology, migration and fate of this novel group of cells. The first neurons
      detected in the rostral prosencephalon with acetylcholinesterase and anti-beta
      tubulin antibody are localized in the olfactory placodes at embryonic day 11 in
      the rate. At embryonic day 12, anti-beta-tubulin antibody-positive cells were
      observed in the mesenchymal tissue between the olfactory pit and the rostral pole
      of the telencephalic vesicle. Anti-beta-tubulin antibody-positive cells were seen
      running superficially over the pial (dorsal) side of the telencephalic vesicle at
      embryonic day 13. The majority of these cells have a bipolar profile with short
      leading and trailing processes, suggesting that they are migratory elements.
      However, some of these cells showed elaborate processes extending for quite long
      distances, overlying the pial surface of the telencephalic vesicle. A mass of
      cells extending over the telencephalic vesicle from the developing olfactory
      epithelium were observed at embryonic day 13 using acetylcholinesterase
      histochemistry. Some of these acetylcholinesterase-positive cells were identified
      as neurons with the specific neuronal marker anti-beta-tubulin antibody. On
      embryonic day 12, neurons from the olfactory epithelium send axonal fibers toward
      the telencephalic vesicles. Most of these fibers spread over the anteroventral
      pole of the vesicles but others entered deep into the telencephalon, reaching the
      germinal ventricular zone. We also show that fibers run rostrocaudally over the
      surface of the telencephalic vesicles. We suggest that these cells and fibers,
      apparently originating in the olfactory placode and migrating through non
      conventional routes, might play a significant role in the earliest stages of
      telencephalic vesicle development.

PMID- 8544991
TI  - Oestradiol acutely stimulates exocytosis of oxytocin and vasopressin from
      dendrites and somata of hypothalamic magnocellular neurons.
AB  - Oestrogen has many direct or indirect actions upon the magnocellular system of
      the hypothalamus. We have examined the possibility of acute actions of oestrogen
      upon the magnocellular system by stimulating slices of supraoptic nucleus in
      vitro with various concentrations of oestrogen, for varying lengths of time, and
      assessing the intrahypothalamic release of oxytocin and vasopressin under these
      conditions. Slices were stimulated in the presence of tannic acid, which
      precipitates extracellular protein and thereby stabilizes exocytosed
      neurosecretory granule cores. Stimulation for 5 or 20 min of slices of
      hypothalamus containing the supraoptic nuclei with 2.66 nM-26.6 microM 17 beta
      oestradiol benzoate caused the exocytosis of granules from both dendrites and
      cell bodies of the magnocellular neurons; exocytosis from the dendrites
      predominated. Granules of both oxytocin- and vasopressin-producing cells were
      exocytosed to a similar extent. The incidence of exocytosis of both hormones
      after stimulation by oestrogen was significantly higher than after exposure
      either to physiological saline or to 17 alpha-oestradiol, but significantly lower
      than after stimulation by 56 mM potassium. The various doses of steroid and
      durations of stimulation all resulted in similar amounts of captured exocytosis.
      Furthermore, the oestradiol-induced release was not inhibited by removal of
      extracellular calcium, whereas the potassium-stimulated release was abolished.
      Exposure for 20 min to either testosterone or progesterone did not induce
      intranuclear release of significant numbers of neurosecretory granules from the
      magnocellular neurons. In contrast to its effect on the hypothalamus, 26.6 microM
      oestradiol for either 20 min or 5 min did not induce exocytosis of neurosecretory
      granules from the posterior pituitary. We conclude that oestrogen can exert acute
      non-genomic actions on the magnocellular neurons to promote intrahypothalamic
      release of oxytocin and vasopressin. This effect is probably direct on the
      magnocellular neurons as it is not dependent on external calcium. Such actions
      may be important in the development of the functional and morphological
      plasticity of the magnocellular system that occurs in parturition and lactation.

PMID- 8544993
TI  - Kappa opioid receptors participate in nerve growth factor-induced hyperalgesia.
AB  - It has recently been observed that nerve growth factors induces the rapid onset
      of thermal hyperalgesia, and the more delayed onset of mechanical hyperalgesia
      when administered to mature rats. Though several mechanisms have been proposed to
      explain this phenomenon, it is still not well understood. Previous studies have
      shown that nerve growth factor can directly excite nociceptive sensory ganglion
      neurons in culture via activation of kappa excitatory opioid receptors. The
      possible involvement of these excitatory opioid receptors in mediating the
      hyperalgesia was investigated. Nerve growth factor-induced thermal hyperalgesia
      in rodents was prevented by co-administration of the non-selective opiate
      antagonist naloxone, as well as by the kappa-selective antagonist nor
      binaltorphimine. Addition of the long-acting opioid antagonist, naltrexone,
      partially prevented mechanical hyperalgesia. Administration of low dose dynorphin
      to mice (a selective kappa-receptor agonist) mimicked the hyperalgesia effects of
      nerve growth factor. Opiate antagonists and anti-nerve growth factor antibody
      both interfered with Freund's adjuvant-induced inflammatory hyperalgesia.
      Altogether, these observations suggest that activation of excitatory opioid
      receptors plays a role in mediating nerve growth factor-induced hyperalgesia and
      that, in turn, nerve growth factor contributes to the hyperalgesia associated
      with inflammatory states. Since opioid receptor antagonists are well tolerated
      clinically, they may be useful for patients receiving nerve growth factor as part
      of ongoing trials of the factor in peripheral neuropathy.

PMID- 8544992
TI  - Effects of L-DOPA on preproenkephalin and preprotachykinin gene expression in the
      MPTP-treated monkey striatum.
AB  - The cellular expression of the genes encoding the neuropeptides enkephalin and
      substance P were examined in the caudate nucleus and putamen of parkinsonian 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys by
      in situ hybridization using radioactive antisense oligonucleotides coupled with
      computer-assisted image analysis. Behavioural evaluation of the animals revealed
      two levels of motor impairment; one group moderately impaired and the other
      severely disabled. A marked increase in the cellular content of preproenkephalin
      A messenger RNA was observed in medium-sized (106 +/- 9 microns2) cells in the
      caudate-putamen of all MPTP animals when compared with controls, the increase
      being greatest in the most severely impaired animals. By contrast, a marked
      reduction in the cellular abundance of preprotachykinin gene expression was
      detected in striatal cells (101 +/- 16 microns2) of these same MPTP animals.
      These changes in neuropeptide gene expression were not associated with a change
      in the density (approximately 10 cells per mm2) of messenger RNA-expressing
      cells. L-DOPA treatment of two of the severely-impaired MPTP monkeys resulted in
      a dissociation of expression of these two genes: the cellular abundance of
      preproenkephalin A remained elevated whilst preprotachykinin levels were
      normalized and comparable with controls. No change in the cellular abundance of
      preprotachykinin messenger RNA was observed in cells of the insular cortex or a
      small discrete population of large cells (208 +/- 27 microns2) in the ventral
      putamen. These results demonstrate that MPTP treatment of primates results in a
      marked potentiation in preproenkephalin messenger RNA coupled with a attenuation
      in preprotachykinin messenger RNA in the dopamine-denervated caudate-putamen. L
      DOPA therapy given on an intermittent schedule reverses the decrease in
      preprotachykinin messenger RNA, but fails to reverse the increase in
      preproenkephalin messenger RNA in the same animal. These observations suggest
      that a dissociation of the activity of these two neuropeptide systems may
      underlie the improvement in motor skill that accompanies dopamine replacement
      therapy and that this dissociation may be instrumental in the long-term
      complications associated with L-DOPA therapy.

PMID- 8544994
TI  - The effects of extrasynaptic substance P on nociceptive neurons in laminae I and
      II in rat lumbar spinal dorsal horn.
AB  - Inflammation of the skin induces release and extrasynaptic spread of
      neuropeptides such as substance P mainly in spinal laminae I and II and causes
      changes in discharge properties of nociceptive neurons in spinal dorsal horn. To
      evaluate the role of extrasynaptic substance P we have superfused the spinal cord
      at recording segment with artificial cerebrospinal fluid or with substance P. A
      total of 102 multireceptive neurons responding to both noxious and innocuous skin
      stimulation were recorded in laminae I or II of lumbar spinal dorsal horn in
      pentobarbital anaesthetized rats. During superfusion with substance P (10 or 100
      microM) significant increases of background activities (from 2.2 +/- 0.6 to 8.4
      +/- 3.2 imp./s, mean +/- S.E.M.), enlargement of cutaneous receptive fields (from
      359.9 +/- 60.4 to 465.5 +/- 77.3 mm2) and enhanced responses to mechanical (from
      89.1 +/- 22.7 to 147.0 +/- 27.5 imp./5 s) but not thermal noxious skin stimuli
      were observed in the 22 neurons tested. Noxious heat-evoked responses and C-fibre
      evoked responses were changed in both directions. In 50 other neurons, the
      coefficients of dispersion of interspike intervals, which is an indicator of
      burst-like discharges, were significantly reduced (from 60.4 +/- 5.5 to 52.7 +/-
      5.3) after application of substance P. Substance P induced oscillations in
      background activities in 13 of 40 non-rhythmic neurons and depressed oscillations
      in 2 of 11 neurons. Cross-correlations of discharges of pairs simultaneously
      recorded neurons were flat (n = 4), or had a central peak (n = 19) or a central
      trough (n = 2) and were not changed qualitatively by extrasynaptic substance P.
      Thus, extrasynaptic substance P can modify not only discharge patterns in the
      spinal dorsal horn.

PMID- 8544995
TI  - Effect of administration of high dose intrathecal clonidine or morphine prior to
      sciatic nerve section on c-Fos expression in rat lumbar spinal cord.
AB  - The effects of moderate and high intrathecal doses of clonidine, an alpha 2
      adrenoceptor agonist, or a high dose of morphine on sciatic nerve section-induced
      expression of c-Fos-like immunoreactivity was studied in laminae I and II of the
      dorsal horn and laminae VIII and IX of the ventral horn of rat lumbar spinal
      cord. c-Fos-like immunoreactivity was examined by immunohistochemistry in normal
      rats (group 1), rats implanted with an intrathecal catheter with its tip on the
      lumbar spinal cord (group 2), injected with 10 micrograms (group 3) or 50
      micrograms (group 4) clonidine intrathecally 3 h before being killed. In other
      groups, saline, 10 or 50 micrograms clonidine or 30 micrograms morphine was
      injected 1 h before unilateral nerve section, and the expression of c-Fos-like
      immunoreactivity was examined 2 h after axotomy. Few labeled neurons were found
      in normal controls. The intrathecal catheter itself caused a significant increase
      in bilateral c-Fos-like immunoreactivity in spinal dorsal and ventral horn
      compared to normals. The level of c-Fos-like immunoreactivity after 10 or 50
      micrograms intrathecal clonidine was similar as in the intrathecal catheter
      group. Sciatic nerve section caused a significant ipsilateral increase in c-Fos
      like immunoreactivity in the dorsal horn compared to the intact side in rats
      injected with saline. Pretreatment with 10 or 10 micrograms clonidine did not
      reduce sciatic nerve section-induced expression of c-Fos-like immunoreactivity,
      but instead caused a significant bilateral increase in c-Fos-like
      immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8544996
TI  - Distribution of neuropeptide FF (FLFQPQRFamide) receptors in the adult rat spinal
      cord: effects of dorsal rhizotomy and neonatal capsaicin.
AB  - By using quantitative autoradiography and highly selective iodinated ligands, we
      quantified modifications in neuropeptide FF binding sites in the superficial
      layers (laminae I and II) of the cervical (C6-C8 segments) and lumbar (L3-L5
      segments) enlargements in two models: (i) rats neonatally treated with capsaicin;
      (ii) rat submitted 15 days before to unilateral dorsal rhizotomies. We
      comparatively analysed the distribution of mu-opioid binding sites in the same
      animals. We have shown that the [125I]YLFQPQRFamide (neuropeptide FF sites)
      labelling is not significantly modified following selective damage of fine
      afferent fibres by neonatal capsaicin treatment. In the cervical and lumbar
      enlargements, capsaicin-treated/control binding ratios for [125I]YLFQPQRFamide
      were 0.90 and 0.86, respectively. While unilateral dorsal rhizotomy induced a
      drastic decrease in [125I]FK-33-824 labelling in the side ipsilateral to the
      lesion as compared to the intact side of (yielding ratios of 0.29 and 0.31 for
      cervical and lumbar levels, respectively), [125I]YLFQPQRFamide labelling was not
      significantly modified, yielding ratios of 0.98 and 0.91 for cervical and lumbar
      levels, respectively. These data suggest that, in contrast with a majority of mu
      opioid receptors, neuropeptide FF receptors are not located on fine primary
      afferent fibers carrying nociceptive information from the fore- or hindlimb in
      the rat. This preferential postsynaptic localization, together with the reported
      "morphine modulating" action of this peptide, support the proposal of a role for
      neuropeptide FF in intraspinal modulation of nociceptive input.

PMID- 8544997
TI  - Effects of upper cervical spinal cord stimulation on neurons in the lumbosacral
      enlargement of the cat: spinothalamic tract neurons.
AB  - Extracellular microelectrode recordings were made from deep spinothalamic tract
      neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and
      paralyzed with gallamine triethiodide. The effects of upper cervical spinal cord
      stimulation were tested on 43 spinothalamic tract neurons, by stimulation of the
      ipsilateral dorsolateral funiculus at C3 and rostral C1 using five or six shocks
      at 333 Hz. The strength of cervical stimulation was adjusted so that the C3 shock
      was above threshold for antidromic activation of spinocervical tract neurons but
      the same strength of shock applied at C1 was below threshold for the same
      neurons. Four of the 43 spinothalamic cells (9%) were not influenced by upper
      cervical stimulation. The remaining 39 spinothalamic tract cells (91%) were all
      excited from the upper cervical cord. Twenty-seven of these (63%) were excited
      more strongly from C3 than from C1, 4 (9%) were excited more strongly from C1
      than from C3, and the remaining eight cells (19%) showed no significant
      differences between their responses to stimulation at C1 and C3. There were no
      obvious differences between those spinothalamic tract neurons showing
      differential effects from C1 and C3 and those showing no such effects. The
      neuronal systems possibly responsible for the differential effects from C3 and C1
      on spinothalamic tract neurons are discussed. We conclude that the most likely
      candidate system for the greater excitation from C3 compared with C1 is the
      subset of spinocervical tract neurons with axon collaterals in the lumbosacral
      enlargement and that the spinothalamic tract is a further ascending path, in
      addition to the postsynaptic dorsal column path, that receives excitatory input
      from spinocervical axon collaterals. The greater excitation from C1 compared with
      C3 is interpreted as due to excitation from C1 and a mixture of excitation and
      inhibition from C3. The responsible neuronal systems seem likely to be either the
      spinocervical neurons with axon collaterals operating on the spinothalamic tract
      via inhibitory interneurons, or cells in the lateral cervical nucleus with axons
      descending to the lumbosacral cord.

PMID- 8544998
TI  - Excitation of sympathetic preganglionic neurons via metabotropic excitatory amino
      acid receptors.
AB  - The role of excitatory amino acid metabotropic receptors in the regulation of
      excitability of sympathetic preganglionic neurons was investigated. This study
      used both conventional intracellular and whole-cell patch clamp techniques to
      record from sympathetic preganglionic neurons in transverse spinal cord slices of
      the rat (9-21 days old). The metabotropic receptor agonists (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (10-200 microM, superfused
      for 2-60 s) and quisqualate (1-50 microM, superfused for 2-60 s) induced
      concentration-dependent depolarizing responses which did not desensitize. These
      responses were unaffected by the glutamate ionotropic receptor antagonists 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-50 microM), 6,7-dinitroquinoxaline
      2,3-dione (DNQX, 10 microM), dizocilpine (MK-801, 10-40 microM), 3-[(R)-2-carboxy
      piperazin-4-yl]-propyl-1-phosphonic acid (D-CPP, 10-50 microM) and DL-2-amino-5
      phosphonovaleric acid (DL-AP5, 20-100 microM). Depolarizing responses to 1S,3R
      ACPD and quisqualate were unaffected by L-2-amino-3-phosphonopropionic acid (L
      AP3, 30 microM-1mM) and L-2-amino-4-phosphonobutanoic acid (L-AP4, 100 microM-1
      mM)). The responses to 1S,3R-ACPD and quisqualate were reduced by including the G
      protein blocker GDP-beta-S (400 microM) in the patch pipette solution by 77 +/-
      2% (mean +/- S.E) of control (n = 3), suggesting that these agonists activate a G
      protein-coupled receptor. Metabotropic receptor-mediated responses were
      maintained in the presence of tetrodotoxin (500 nM), progressively reduced with
      increased membrane hyperpolarization to around -95 mV and associated with either
      an increase of 16.5 +/- 2.8% (data from four neurons) in the majority of neurons
      (n = 22 of 34) or no measurable change (n = 12) in neuronal input resistance.
      These data suggest that the agonists exert a direct action on 1S,3R-ACPD and
      quisqualate had several effects on sympathetic preganglionic neuron membrane
      properties including: inhibition of a slow apamin-insensitive component of the
      afterhyperpolarization; a reduction in spike frequency adaptation leading to
      increases in firing frequency from 6.4 +/- 2.8 Hz in control experiments up to
      14.7 +/- 3.0 Hz (n = 6 neurons) in the presence of a metabotropic receptor
      agonist: a broadening of the action potential by 37.5 +/- 6.4% (n = 6 neurons) of
      control. These observations suggest that the metabotropic receptor-mediated
      depolarization is due, at least in part, to the reduction of potassium
      conductances involved in the spike afterhyperpolarisation potential.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8544999
TI  - Neurochemical, electrophysiological and immunocytochemical evidence for a
      noradrenergic link between the sympathetic nervous system and thymocytes.
AB  - The object of these experiments was to investigate whether noradrenaline is the
      signal neurotransmitter between the sympathetic nervous system and rat
      thymocytes. Using immunocytochemistry, evidence was obtained that the rat thymus
      (thymic capsule, subcapsular region and connective tissue septa) is innervated by
      noradrenergic varicose axons terminals (tyrosine hydroxylase- and dopamine-beta
      hydroxylase-immunostained nerve fibres). This innervation is mainly associated
      with the vasculature and separately from vessels along the thymic tissue septa it
      branches into the thymic parenchyma. Using electron microscopy, classical
      synapses between thymocytes and neuronal elements were not observed. The
      neurochemical study revealed that these nerve terminals are able to take up,
      store and release noradrenaline upon axonal stimulation in a [Ca2+]o-dependent
      manner. The release was tetrodotoxin (1 microM)-sensitive, and reserpine
      pretreatment prevented axonal stimulation to release noradrenaline, indicating
      vesicular origin of noradrenaline. In addition, it was found that the release of
      noradrenaline was subjected to negative feedback modulation via presynaptic alpha
      2-adrenoreceptors. Using a patch-clamp technique, electrophysiological evidence
      was obtained showing that noradrenaline inhibits in a concentration-dependent
      manner outward voltage-dependent potassium (k+) current recorded from isolated
      thymocytes. Since noradrenergic varicose axon terminals enter the parenchyma
      thymocytes and the boutons are not in close apposition to their target cells,
      noradrenaline released from these terminals diffuses away from release site to
      reach its targets, thymocytes, and to exert its inhibitory effect on voltage
      dependent K+ -current. Since K+ channels are believed to be involved in T cell
      proliferation and differentiation, the modulation of K+ channel gating by
      noradrenaline released in response to axonal activity suggests that signals from
      blood-born or locally released hormones and cytokines. In this respect,
      noradrenaline released from non-synaptic neuronal varicosities and exerting its
      effect within the radius of diffusion may serve as a chemical link between the
      sympathetic nervous system and thymocytes and may have physiological and
      pathological importance in the thymus during stress and inflammatory/immune
      responses.

PMID- 8545000
TI  - Transneuronal labeling in hamster brainstem following lingual injections with
      herpes simplex virus-1.
AB  - Brainstem projections to hypoglossal motoneurons innervating the intrinsic and
      extrinsic muscles of the tongue were determined using the transneuronal transfer
      of Herpes simplex virus-1. Injections of Herpes simplex virus-1 into the
      intrinsic muscles of the anterior tongue, the geniohyoid and styloglossus muscles
      each produced specific patterns of label within the hypoglossal nucleus that
      corresponded closely to the distributions of retrogradely labeled neurons
      produced by similar injections of horseradish peroxidase. With relatively short
      survival times, Herpes simplex virus-1 injections further labeled neurons in both
      the brainstem reticular formation lateral to the hypoglossal nucleus and in the
      nucleus of the solitary tract. Intrinsic lingual muscles injections of Herpes
      simplex virus-1 labeled reticular formation neurons distributed laterally along
      the entire anterior-posterior length of hypoglossal nucleus. In contrast, labeled
      reticular formation neurons in the immediate vicinity of the hypoglossal nucleus
      following extrinsic muscles injections, were located lateral to intermediate and
      anterior levels of hypoglossal nucleus. Thus, despite extensive areas of overlap,
      there was evidence for a differential distribution of pre-hypoglossal reticular
      formation neurons along the anterior-posterior axis associated with different
      lingual injections. Most of the overlap occurred anteriorly, at a level where the
      nucleus of the solitary tract abuts the fourth ventricle. The potential
      importance of this area is lingual integrative function was further suggested by
      camera lucida reconstructions that showed overlapping dendritic fields of labeled
      neurons in the reticular formation and nucleus of the solitary tract. The
      dendritic fields of other labeled neurons located more rostral and lateral in the
      reticular formation sometimes extended into the rostral (gustatory) nucleus of
      the solitary tract and spinal trigeminal nuclei, suggesting possible
      multisynaptic pathways through which tactile and gustatory information might
      influence hypoglossal nucleus. Not all injections of Herpes simplex virus-1
      produced label in the hypoglossal nucleus. Some injections into the anterior
      tongue labeled neurons in the reticular formation near the exiting facial nerve,
      a region containing populations of preganglionic parasympathetic neurons. Other
      injections, particularly into the extrinsic lingual muscles, labeled brainstem
      neurons associated with the sympathetic nervous system, e.g. nuclei raphe magnus
      and pallidus, the rostral ventrolateral reticular formation, and neurons in the
      A5 region. These patterns of labeled neurons within the brainstem are suggestive
      of a differential autonomic innervation of the intrinsic and extrinsic muscles of
      the tongue.

PMID- 8545001
TI  - Recycling of L-citrulline to sustain nitric oxide-dependent enteric
      neurotransmission.
AB  - Neurons that synthesize nitric oxide from arginine produce stoichiometric amounts
      of citrulline. We investigated whether nitric oxide-releasing enteric neurons
      have the capacity to recycle citrulline to arginine and thereby sustain nitrergic
      neurotransmission. Argininosuccinate synthetase-like immunoreactivity and
      argininosuccinate lyase-like immunoreactivity, enzymes capable of citrulline to
      arginine conversion, were both localized in discrete populations of myenteric and
      submucosal neurons in the canine proximal colon. Argininosuccinate synthetase
      like immunoreactivity and argininosuccinate lyase-like immunoreactivity co
      localized with neuronal beta-nicotinamide adenine dinucleotide phosphate
      diaphorase staining, a marker for nitric oxide synthase. The functional
      significance of argininosuccinate synthetase-like immunoreactivity and
      argininosuccinate lyase-like immunoreactivity was shown by testing the effects of
      exogenous citrulline on responses to enteric inhibitory nerve stimulation, which
      were assessed by measuring contractions, inhibitory junction potentials and
      electrical slow waves. As shown previously, arginine analogues (L-nitroarginine
      methyl ester or L-nitroarginine; 100 microM) inhibited nitric oxide-dependent
      responses, and excess L-arginine restored inhibitory responses. Citrulline alone
      (0.1-2 mM) had no effect on nitrergic transmission under control conditions, but
      in the presence of L-nitroarginine methyl ester or L-nitroarginine, citrulline
      (0.1-2 mM) restored nitrergic transmission in a concentration-dependent manner.
      Other neutral amino acids (L-serine, L-leucine) did not mimic the effects of
      citrulline. Taken together, these data suggest that enteric nitrergic neurons
      have the enzymatic apparatus and functional capability of recycling citrulline to
      arginine.

PMID- 8545002
TI  - Asymmetrical involvement of mesolimbic dopaminergic neurons in affective
      perception.
AB  - Pharmacological studies suggest that increases and decreases in dopamine levels
      in the nucleus accumbens contribute to positive and negative affective states,
      respectively. In vivo neurochemical investigations have led to contradictory
      conclusions, since increases and decreases in dopamine release have been observed
      in aversive situations. Clinical and experimental observations argue for a
      hemispheric asymmetry in the processing of appetitive and aversive stimuli.
      Mesolimbic dopaminergic neurons are part of integrative networks which appear
      specifically organized in the right and left hemispheres. Dopaminergic neurons
      may thus be involved in affective processes but in a different manner in the two
      hemispheres. We tested this hypothesis in the nucleus accumbens of male rats
      using in vivo voltammetry and a conditioned aversion paradigm to an olfactory
      stimulus. We found that dopaminergic responses were similar in the two
      hemispheres following the initial encounter with the stimulus. After
      conditioning, however, dopaminergic responses to a naturally attractive olfactory
      stimulus were more elevated in the right nucleus accumbens and responses to an
      aversive stimulus more marked in the left nucleus. In addition, dopaminergic
      responses displayed an intraaccumbal regionalization, in particular opposite
      variations were obtained in the core and shell subterritories in response to the
      aversive situation. These results may provide new insights in the understanding
      of the relative contribution of the two hemispheres in affective perception in
      normal and psychopathological conditions.

PMID- 8545003
TI  - Influence of neurotrophic factors on morphine- and cocaine-induced biochemical
      changes in the mesolimbic dopamine system.
AB  - Previous research has shown an increase in tyrosine hydroxylase in the ventral
      tegmental area following chronic morphine and chronic cocaine treatments. Chronic
      morphine treatment also increases levels of glial fibrillary acidic protein in
      this brain region. In the present study, we investigated the effects of infusing
      neurotropic factors (nerve growth factor, brain-derived neurotrophic factor,
      neurotrophin-3, neurotrophin-4 or ciliary neurotrophic factor) via midline intra
      ventral tegmental area cannulae on these biochemical changes. Our studies
      examined the effects of neurotrophic factor infusion alone, neurotrophic factor
      infusion followed by morphine treatment, morphine treatment followed by
      neurotrophic factor infusion, and concurrent neurotrophic factor infusion and
      cocaine treatment. Brain-derived neurotrophic factor, which by itself tended to
      decrease tyrosine hydroxylase levels in the ventral tegmental area, prevented the
      characteristic increase in tyrosine hydroxylase following morphine and cocaine
      exposure and reversed the increase in rats pretreated with morphine. Neurotrophin
      4 and neurotrophin-3 exerted similar effects. In addition, neurotrophin-4
      prevented the morphine-induced increase in glial fibrillary acidic protein. In
      contrast, ciliary neurotrophic factor infusions alone resulted in an increase in
      tyrosine hydroxylase levels, with no additional increase induced by morphine or
      cocaine coadministration. Nerve growth factor alone had no effect on tyrosine
      hydroxylase or glial fibrillary acidic protein levels and did not affect
      morphine's ability to induce these proteins. We also looked at the effects of
      intra-ventral tegmental area infusion of neurotrophic factor on cAMP-dependent
      protein kinase and adenylyl cyclase activity in the nucleus accumbens, both of
      which are increased by chronic morphine or cocaine exposure. In general,
      regulation of cAMP-dependent protein kinase and adenylyl cyclase morphine by
      neurotrophic factors paralleled effects seen in the ventral tegmental area. Intra
      ventral tegmental area infusion of brain-derived neurotrophic factor (or
      neurotrophin-4) alone tended to decrease cAMP-dependent protein kinase and
      adenylyl cyclase activity in the nucleus accumbens and prevented the morphine
      induced increases in these enzymes. These effects were not seen with ciliary
      neurotrophic factor or nerve growth factor. These studies demonstrate novel
      interactions within the ventral tegmental area, and its target the nucleus
      accumbens, between neurotrophic factors and drugs of abuse, which have
      potentially important implications for the pathophysiology and treatment of drug
      addiction.

PMID- 8545004
TI  - Glucose injections into the medial septum reverse the effects of intraseptal
      morphine infusions on hippocampal acetylcholine output and memory.
AB  - Morphine infusions into the medial septum produce memory deficits which can be
      attenuated by concurrent intraseptal injections of glucose. The mnemonic deficits
      following intraseptal morphine injections may be due, in part, to opioid
      inhibition of cholinergic neurons projecting to the hippocampus, with glucose
      reducing the effect. The present experiment determined whether glucose injections
      into the medial septum attenuate the effects of intraseptal morphine injections
      on hippocampal acetylcholine release and on memory. Samples of extracellular
      acetylcholine levels were assessed at 12 min intervals using in vitro
      microdialysis with high-performance liquid chromatography with electrochemical
      detection. Intraseptal morphine injections (4.0 nmol) reduced acetylcholine
      output starting at 12 min and lasting up to 72 min post-injection. Glucose (18.3
      nmol) injected concomitantly with morphine reversed the drug infusions in the
      septum 20 min prior to spontaneous alternation testing. Intraseptal morphine
      infusions reduced alternation scores; this behavioral effect was reversed by
      concurrent glucose infusions. The effect of drugs infused into the septal area on
      spontaneous alternation performance and acetylcholine output were positively
      correlated. These findings suggest that memory deficits induced by intraseptal
      morphine injections may result, at least partially, from a decrease in the
      activity of cholinergic neurons and that this effect is reversed by glucose.

PMID- 8545005
TI  - Metabotropic glutamate receptor subtypes differentially influence neuronal
      recovery from in vitro hypoxia/hypoglycemia in rat hippocampal slices.
AB  - Hippocampal slices were transiently exposed to an oxygen- and glucose-free
      environment which causes a pronounced drop of both ATP and creatine phosphate, an
      anoxic depolarization, and an incomplete recovery of synaptically evoked
      population spike in the CA1 region after 1 h (48.5 +/- 3.6% of baseline values).
      This recovery could be markedly enhanced by the application of N-methyl-D
      aspartate receptor antagonists. To examine the influence of metabotropic
      glutamate receptors on neuronal recovery from hypoxia/hypoglycemia, we applied
      various antagonists and agonists of the metabotropic glutamate receptors to the
      bath during the interval from 20 min before to 10 after hypoxia/hypoglycemia. The
      metabotropic glutamate receptor antagonists (+)-alpha-methyl-4
      carboxyphenylglycine and L-2-3- amino-phosphonopropionic acid were both able to
      enhance the population spike recovery significantly. However, the mixed
      metabotropic glutamate receptor agonist 1S,3R-1-aminocyclopentane-1,3
      dicarboxylic acid also exhibited a protective effect on population spike
      recovery, leaving the anoxic depolarization and N-methyl-D-aspartate responses
      during the hypoxia/hypoglycemia untouched. With the help of more subtype-specific
      agonists, we found that an activation of phospholipase C coupled (class 1)
      metabotropic glutamate receptors prior to hypoxia/hypoglycemia may be responsible
      for the protective effect seen with 1S, 3R-1-aminocyclopentane-1,3-dicarboxylic
      acid, because the specific class 1 metabotropic glutamate receptor agonist trans
      azetidine-2,4-dicarboxylic acid appeared to be highly protective, but only if it
      was applied 20 min before the hypoxia/hypoglycemia. An activation of class 2
      metabotropic glutamate receptors by (2S,1'R,2'R,3'R)-2-(2,3
      dicarboxycyclopropyl)glycine, which inhibits adenylyl cyclase activity, led to a
      marked deterioration of the population spike recovery and even to a total
      prevention of the protective effect of the N-methyl-D-aspartate agonist D-2-amino
      5-phosphonopentanoic acid. Our data suggest that prior activation of class 1
      metabotropic glutamate receptors is beneficial, while their activation during
      hypoxia/hypoglycemia is detrimental. Furthermore, the activation of class 2
      metabotropic glutamate receptors decreases the recovery from
      hypoxia/hypoglycemia.

PMID- 8545006
TI  - Updated proceedings of the 2nd International Conference on the Varicella-Zoster
      Virus. Paris, France, July 7-8, 1994.

PMID- 8545007
TI  - From molecular biology to medicine: two decades of achievement in varicella
      zoster virus research.

PMID- 8545008
TI  - Molecular basis for a geographic variation of varicella-zoster virus recognized
      by a peptide antibody.
AB  - A live attenuated varicella vaccine, derived from a Japanese isolate, is
      currently being widely used to modulate disease caused by varicella-zoster virus.
      Differentiation of the vaccine from wild-type isolates has been and will continue
      to be critical in the assessment of the vaccine in the United States. This has
      largely relied upon identification of characteristic DNA polymorphisms in the
      vaccine strain in the United States. This has largely relied upon identification
      of characteristic DNA polymorphisms in the vaccine strain. In this report, we
      describe the identification of a new sequence polymorphism, located in the N
      terminal coding sequence of open reading frame (ORF) 10. This variation results
      in the synthesis of an ORF 10 protein that is differentially recognized by
      antibodies to an ORF 10 synthetic peptide. The variation appears to be completely
      restricted to Japanese strains, including that used for the live attenuated
      varicella vaccine. As such, this polymorphism and the antibodies that
      differentially recognize it could prove highly useful in the assessment of the
      Japanese vaccine in the United States.

PMID- 8545010
TI  - Varicella-zoster virus latency in the adult rat is a useful model for human
      latent infection.
AB  - A model of latent infection by varicella-zoster virus (VZV) was obtained in the
      adult rat. Inoculation of VZV-infected cells in the skin led to infection of the
      peripheral nervous system. Latency was characterized by a long-lasting presence
      of the viral genome, of selected viral gene transcripts, and of at least one
      viral protein in the dorsal root ganglia. Reactivation has not been obtained in
      vivo, but has occurred ex vivo after repeated stresses. Many similarities with
      VZV latency in humans were found, making this model useful for vaccine and
      antiviral studies.

PMID- 8545009
TI  - Entry and egress of varicella-zoster virus: role of mannose 6-phosphate, heparan
      sulfate proteoglycan, and signal sequences in targeting virions and viral
      glycoproteins.

PMID- 8545011
TI  - Varicella-zoster virus ocular infection in the rabbit: a model of human zoster
      ophthalmicus.

PMID- 8545012
TI  - Varicella-zoster virus gene regulation.
AB  - The varicella-zoster virus genome contains 71 open reading frames (ORFs), five of
      which (ORF62, ORF4, ORF63, ORF61, and ORF10) encode regulatory proteins. ORF62
      codes for the major immediate early protein of the virus exhibiting DNA-binding
      and regulatory functions. This protein, localized in the cell nucleus, is a
      functional homologue to ICP4 of herpes simplex virus type 1 (HSV-1). It trans
      activates several varicella-zoster virus promoters of the various gene classes
      and autoregulates its own expression. ORF4 protein activates gene promoters
      provided they have basal activities, but it is not a functional homologue of HSV
      1 ICP27. Gene regulation activity appears to be linked to its cysteine-rich C
      terminal region. ORF63 codes for an immediate early protein mainly located in the
      cell nucleus. The regulatory functions it performs are still unclear. ORF61
      protein is the functional homologue of HSV-1 ICP0. Its N-terminal region exhibits
      a RING domain responsible for trans-activating and trans-repressing activities.
      ORF10 protein exhibits similarities with HSV-1 VP16 and activates the ORF62
      promoter.

PMID- 8545013
TI  - Analysis of varicella-zoster virus promoter sequences.

PMID- 8545014
TI  - Interactions between varicella-zoster virus IE62 and cellular transcription
      factor USF in the coordinate activation of genes 28 and 29.
AB  - Varicella-zoster virus (VZV) gene 28 encodes the viral DNA polymerase, while 29
      encodes the major DNA-binding protein. Because of the central importance of these
      proteins to productive replication of VZV and because, of these, only gene 29
      seems to be expressed in latency, we sought to understand how their expression is
      controlled. We recently reported that the divergent gene 28 and gene 29
      transcripts are coordinately upregulated by IE62. Deletions in the 221-bp
      promoter domain shared by genes 28 and 29 comparably diminish the expression of
      both genes. By a variety of transient expression, competition gel shift, and
      super-shift assays, we now show that cellular transcription factor USF binds to a
      palindromic recognition sequence lying equidistant from transcription start sites
      for both genes 28 and 29. In the presence of IE62, USF fully activates
      transcription of genes 28 and 29. Site-specific mutation of three bases in the
      USF core binding hexamer abrogates activation of the gene 28 and 29 promoters by
      IE62. USF is important for expression of genes 28 and 29 in productive VZV
      infection.

PMID- 8545015
TI  - Transcriptional mapping of varicella-zoster virus regulatory proteins.
AB  - Varicella-zoster virus (VZV) expresses four proteins that influence viral
      transcriptional events and that also are homologous to herpes simplex virus type
      1 (HSV-1) immediate-early proteins. However, their transcription and the
      mechanisms by which it is regulated are not yet resolved. To identify the
      promoter regions, a precise knowledge of the initiation and termination of the
      encoded RNAs is first required. In this report, we summarize the complete and
      precise mapping of the RNA transcripts of two of these genes--those from open
      reading frames 4 and 63. In addition, several elements of their promoter
      regulatory regions have been identified and predicted. Structural and functional
      studies of the regulatory sequences suggest that these two VZV genes may be
      regulated in a fashion different from that of their HSV-1 counterparts.

PMID- 8545016
TI  - Aspects of the host response to varicella-zoster virus: a review of recent
      observations.

PMID- 8545018
TI  - Immunization to reduce the frequency and severity of herpes zoster and its
      complications.
AB  - Herpes zoster (HZ) is a localized disease that results from reactivation of an
      endogenous varicella-zoster virus (VZV) infection that has persisted in latent
      form within sensory ganglia following an earlier attack of varicella. The
      incidence and the severity of HZ and its complications increase with advancing
      age, and this is temporally associated with an age-related decline in cell
      mediated immunity (CMI) to VZV. Information on the cellular site and mechanism of
      VZV latency and on the events that follow reactivation appears to explain many of
      the clinical features of HZ and to provide a pathophysiologic basis for the
      presumption that immunity to VZV plays a critical role in limiting the frequency
      and consequences of VZV reactivation. The close temporal correlation between the
      decline in VZV-specific CMI and the increased frequency and severity of HZ and
      its complications in older individuals suggests that HZ may actually develop
      because VZV-specific CMI falls below some critical threshold. The development of
      a live attenuated varicella vaccine provides a means of stimulating VZV-specific
      CMI and thus of determining its role in the pathogenesis of HZ. Levin and his
      colleagues have demonstrated that waning VZV-specific CMI in elderly persons can
      be stimulated by varicella vaccine to levels typical of those observed in younger
      persons, in whom the incidence and severity of HZ are much reduced. Thus the
      stage is set for a large placebo-controlled clinical trial that will test
      directly the hypothesis that restoration of waning CMI to VZV will reduce the
      frequency and severity of HZ and its complications in the elderly.

PMID- 8545017
TI  - Cytokine production in varicella-zoster virus-stimulated lymphocyte cultures.
AB  - Among varicella-zoster virus (VZV)-immune adults aged 20 to 35 years, T
      lymphocytes producing interferon-gamma (IFN-gamma) in response to a VZV antigen
      stimulus are eight times more numerous than those making interleukin-4 (IL-4). In
      persons over 55 years old, the frequency of IFN-gamma-making cells falls while
      the number of IL-4-making cells remains roughly constant. The persistence of IL-4
      making cells may contribute to the maintenance of IgG antibodies to VZV with
      aging.

PMID- 8545019
TI  - Localization of varicella-zoster virus nucleic acids and proteins in human skin.
AB  - The pathogenic mechanisms involved in varicella-zoster virus (VZV) infections
      remain elusive. The pattern of cutaneous distribution of the IE63 protein and of
      the gpI (gE) and gpII glycoproteins with their corresponding genome sequences
      during VZV infections was studied by immunohistochemistry and in situ
      hybridization. Skin biopsy specimens were obtained from immunocompetent and
      immunocompromised patients with varicella, herpes zoster, or atypical VZV
      lesions. The first evidence for VZV infection consisted of the presence of IE63
      in keratinocytes. In the vesicles and pustules, the viral transcripts gpI, gpII,
      and IE63 and the corresponding nucleic acids for gpI and gpII were identified in
      keratinocytes, sebocytes, Langerhans cells, dermal dendrocytes,
      monocytes/macrophages, and endothelial cells. The gpI and gpII glycorpoteins were
      essentially located on the cellular membranes while IE63 expression was generally
      restricted to the nuclei. In three biopsies of early herpes zoster, viral
      proteins were disclosed in dermal nerves and in perineurial type I dendrocytes.
      This was never encountered in varicella. Vasculitic changes and endothelial cell
      involvement were more prominent in varicella than in herpes zoster. It is
      concluded that the secondary viremia in varicella that affects the dermal
      endothelial cells is followed by a cell-to-cell spread to keratinocytes. In
      herpes zoster, the viral progression through cutaneous nerves primarily extends
      to the pilosebaceous units with a secondary involvement of epidermal
      keratinocytes, followed by a further spread to dermal cells.

PMID- 8545020
TI  - Herpes zoster ophthalmicus.

PMID- 8545021
TI  - Herpes zoster and quality of life: a self-limited disease with severe impact.

PMID- 8545022
TI  - Clinical features and pathophysiologic mechanisms of postherpetic neuralgia.
AB  - Postherpetic neuralgia is an unfortunate aftermath of shingles, and is most
      likely to develop, and most persistent, in elderly patients. Pain, allodynia, and
      sensory loss in the affected dermatome are the cardinal manifestations of the
      disorder. The pathophysiology of postherpetic neuralgia is not well known, but
      recent observations suggest multiple changes in the afferent pathways at both
      peripheral and central nervous system levels.

PMID- 8545023
TI  - Pathophysiology of postherpetic neuralgia: towards a rational treatment.

PMID- 8545024
TI  - The treatment of postherpetic neuralgia.
AB  - Postherpetic neuralgia, when defined as neuropathic pain persisting 1 month or
      longer after herpes zoster infection, affects about 10% of all patients who have
      contracted the disease. The incidence of postherpetic neuralgia increases with
      age; at age 60, about 50% of herpes zoster patients will suffer significant pain,
      and this proportion grows with subsequent decades. If therapy is carefully chosen
      and monitored, it is possible to give satisfactory relief, taking pain from
      severe to mild, to between 60 and 70% of patients. This article will review
      current treatment and focus on antidepressant drugs, treatments that are
      contentious and of current interest such as topical agents, and the use of
      opioids for this type of chronic neuropathic pain.

PMID- 8545025
TI  - How should we measure pain in herpes zoster?
AB  - Pain occurs during the acute phase of herpes zoster and as postherpetic neuralgia
      (PHN) for months or years after the acute illness has healed. The acute pain
      results from viral replication leading to the death of neurons together with
      cutaneous inflammation. However, the exact mechanism of PHN is still conjectural.
      Historically, PHN has been defined as any pain that follows disappearance of the
      rash of herpes zoster, but a number of other definitions (eg, pain present for
      more than 1 or 2 months after rash onset) have also been used. Since pain is
      purely subjective and is usually felt as a continuum, any definition is entirely
      arbitrary and sheds no light upon the pathophysiology of the prolonged pain. An
      arbitrary division of pain poses problems for the measurement of the effect of
      acute therapy upon the duration of PHN. Use of a definition of PHN that involves
      the time of rash healing also leads to considerable difficulties in the
      assessment of therapies that affect the duration of the rash. The median times
      for resolution of both acute pain and PHN are likely to be biased in favor of
      therapy that heals the rash more rapidly, even if the continuum of pain is not
      affected. For these reasons, the term "zoster-associated pain," encompassing both
      the acute and chronic pain associated with herpes zoster, has evolved as a more
      meaningful way of measuring pain both for the individual patient and also for the
      comparison of two potential therapies.

PMID- 8545026
TI  - Mechanical allodynia in postherpetic neuralgia: evidence for central mechanisms
      depending on nociceptive C-fiber degeneration.
AB  - In 12 zoster patients who had developed postherpetic neuralgia with dynamic
      mechanical allodynia and in six zoster patients who had recovered without pain,
      the functional role of nociceptive C-fibers in allodynia was assessed by
      quantifying axon reflex reactions induced by histamine iontophoresis within
      allodynic regions and in their contralateral sites. In patients with postherpetic
      neuralgia, histamine responses were reduced or abolished within allodynic areas,
      indicating degeneration of nociceptive C-fibers. In patients who recovered
      without pain, histamine responses were bilaterally identical, indicating complete
      regeneration of nociceptive C-fibers. These results demonstrate that sensitized
      nociceptive C-fibers are not involved in signaling and maintenance of allodynia.
      Alteration in CNS processing may reorganize synaptic ties between central pain
      signaling pathways and mechanoreceptive A beta-fibers depending on afferent C
      fiber degeneration rather than ongoing C-fiber input.

PMID- 8545027
TI  - Dextromethorphan shows efficacy in experimental pain (nociception) and opioid
      tolerance.
AB  - The oral antitussive dextromethorphan is a clinically available N-methyl-D
      aspartate receptor antagonist. Dextromethorphan has analgesic efficacy in the
      experimental formalin test, blocks the nociceptive activation of the immediate
      early gene, c-fos proto-oncogene, and prevents and reverses the development of
      opiate analgesic tolerance in experimental models. These data suggest that
      dextromethorphan should be evaluated in a controlled clinical trial for analgesic
      efficacy in zoster-associated neuralgia.

PMID- 8545028
TI  - Gene delivery to mouse sensory neurons with herpes simplex virus: a model for
      postherpetic neuralgia and its treatment?

PMID- 8545029
TI  - The future of predictors, prevention, and therapy in postherpetic neuralgia.
AB  - Pain is the most common complication of herpes zoster, but much confusion and
      dissent exist regarding terminology. Established (chronic) herpetic pain is
      remarkably resistant to treatment, but its prevention is partly achievable.
      Prodromal and acute herpetic pain are predictors for chronic pain. If research
      programs and clinical management are to progress optimally, researchers and
      clinicians must agree on appropriate use of such terms as "zoster-associated
      pain" and "postherpetic neuralgia."

PMID- 8545030
TI  - Sorivudine: a promising drug for the treatment of varicella-zoster virus
      infection.
AB  - Sorivudine provides a unique nucleoside analog with significantly enhanced both
      in vitro and in vitro activity and enhanced oral bioavailability. Early
      indications from controlled studies indicate that sorivudine therapy is superior
      to acyclovir for the treatment of localized zoster in individuals with HIV
      infection and adults with chicken pox. However, these studies await peer
      evaluation. Importantly, recent experience in Japan indicates administration of
      sorivudine with 5-fluorouracil (5-FU) is contraindicated. Sorivudine inhibits
      dihydropyrimidine dehydrogenase, which is required for the metabolism of 5-FU. As
      a consequence, toxic levels of 5-FU accumulate in the plasma and have led to the
      deaths of nearly 30 patients in Japan. One might question, as these data unfold,
      the relative value of drugs with such enhanced in vitro activity and oral
      bioavailability as compared with standard therapeutic agents. Should accelerated
      healing occur, but not as dramatically as would have been anticipated from the in
      vitro data, unique approaches to the management of herpes zoster will need to be
      developed if further improvement is desired. Regardless, sorivudine appears
      superior to acyclovir for acceleration of cutaneous healing and, importantly, can
      be administered once daily in significantly smaller concentrations. These
      findings in and of themselves should allow for licensure of the compound in other
      developed societies.

PMID- 8545031
TI  - Efficacy of famciclovir in the treatment of herpes zoster: reduction of pain
      associated with zoster.

PMID- 8545033
TI  - Varicella-zoster virus: History, perspectives, and evolving concerns.

PMID- 8545032
TI  - Prospective epidemiologic study of painful and neurologic sequelae induced by
      herpes zoster in patients treated early with oral acyclovir.
AB  - Three hundred and one patients with acute herpes zoster treated early with oral
      acyclovir were enrolled in an open, prospective study designed to evaluate
      painful and neurologic disorders over a 6-month period. Age, initial pain
      severity, and occurrence of a neurologic deficit influenced the incidence of
      postherpetic neuralgia. No relationship was found between initial rash severity
      and either pain incidence or neurologic deficit.

PMID- 8545034
TI  - [Gn-RH analogs in the treatment of benign gynecologic diseases: current trends].
AB  - Gn-RH analogues have been recently employed for the treatment of oestrogen
      dependent benign gynaecological disorders, such as uterine myomata, endometriosis
      or metrorrhagia. They induce a "pharmacological castration", inducing a marked
      reduction of serum oestrogen levels. They proved more effective than other drugs
      used up to now in the medical treatment of these benign gynaecological diseases.
      Thus they were initially employed in every case. Later it became clear that Gn-RH
      analogues need a selective indication. The authors herein report their series of
      70 patients with benign gynaecological disorders (45 uterine fibroids, 10
      endometriosis, 15 metrorrhagia), treated with a Gn-RH analogue depot for 2-3
      months preoperatively. They evaluated the efficacy of the treatment in the group
      with uterine fibroids in terms of disappearance of metrorrhagia, better
      haemoglobin level in anaemic patients, reduction of fibroids size allowing for a
      simpler and less extensive surgery (vaginal surgery, myomectomy, hysteroscopic
      resection). The authors discuss those cases when preoperative treatment with Gn
      RH analogues is not indicated, or should be employed only under careful
      surveillance (in the preparation of multiple myomectomies, big submucosal
      myomas). In the group of 10 patients with endometriosis we observed the
      disappearance of pelvic pain and dyspareunia, whereas the size of endometriomas
      was only minimally reduced. The authors discuss the usefulness of this treatment
      in case of patients with endometriosis grade I or II (minimal or mild), with
      desire of children. In the group of 15 perimenopausal patients with metrorrhagia,
      10 became amenorrhoic after termination of treatment, thus avoiding surgery. The
      major benefit for the other 5 patients was a better haemoglobin level at the time
      of surgery.

PMID- 8545035
TI  - [Autologous blood collection in pregnancy. Prospective study].
AB  - Autologous blood predonation during pregnancy, with the aim of autotransfusion
      after delivery, has gained increasing consensus over the last few years. However,
      there are still some controversial aspects. In particular, the cost/benefit ratio
      of institutionalizing the above mentioned practice would appear altogether
      unfavourable (too many women would be really in need of transfusion after
      delivery). The aim of the present study is to assess the results of our
      experience using autotransfusion in obstetrics. This longitudinal and prospective
      study was carried out on a sample of 29 pregnant women who donated 1 unit of
      blood during the last month of their pregnancy. Phlebotomy was preceded by a
      verification of the permitting conditions (Hb > or = 11 g/dl; Ht > or = 33%).
      Before, during and after phlebotomy, the patients underwent cardiotocographic
      monitoring and periodic observation of vital parameters. The hematologic
      parameters registered during the various test (before predeposit, before
      delivery, in puerpery) were statistically analysed. The hemochromo values
      appeared satisfactory in all cases at the time of admittance for labour. As a
      consequence of a hematic loss higher than usual at the moment of delivery, in
      many cases the hemoglobin values during puerpery did not enable us to exclude a
      priori the advisability of a transfusion. From the study we see how the
      cost/benefit ratio of the predeposit practice in obstetrics is less unfavourable
      than commonly thought.

PMID- 8545036
TI  - [Blood transfusion in benign obstetric-gynecologic disorders].
AB  - Objective of our study was to determine the incidence of blood transfusions in
      patients treated with abdominal or vaginal surgery for benign pathologies,
      because of high risks (especially infections) connected to this practise, and to
      evaluate the possibility of a simple medical treatment in patients with anemia
      and not to use blood transfusions. Examining our activity in a five-year period,
      from 1988 to 1992, we report that the use of blood was required for only 21
      women, 1.5 percent of patients with gynecological problems (10 over 639) and 0.17
      percent of pregnant patients (11 over 6208). We had more anemia in the abdominal
      approach than in the vaginal way. A group of 20 young women, with the efficient
      cardiovascular system, with severe-mild anemia too, were treated with simple
      medical support, obtaining, in a short time, good clinical conditions.

PMID- 8545037
TI  - [Transvaginal echography in patients with postmenopausal metrorrhagia].
AB  - Forty-one postmenopausal patients with abnormal uterine bleeding were scheduled
      for endometrial sampling in a week from the measurement of endometrial thickness
      by transvaginal ultrasonography. If the cut-off limit was 5 mm, the endometrial
      thickness was correlated with the presence of pathologic endometrium with a
      sensitivity of 87.5%, a specificity of 76%, a positive predictive value of 70%
      and a negative predictive value of 90.5%. Endometrial hyperplasia and polyp
      represented the two false negative cases. Waiting for a study on a sufficiently
      large series, the authors think that also an endometrial thickness of a few
      millimeters doesn't justify the non-recourse to endometrial biopsy in the
      presence of repeated haemorrhagic episodes or specific risk factors.

PMID- 8545038
TI  - [Immigrant women and health services. Experience with hospital obstetric
      gynecologic department (1992-94)].
AB  - In order to know more about immigrant women who have applied for obstetrical and
      gynaecological care and the results of these requests, data on those admitted
      have been analyzed at the obstetric and gynaecological ward of the general
      hospital of Perugia during the period from July 1992 to June 1994. The following
      observations were made: a) African and eastern european women comprised the group
      that most frequently applied for abortion; b) the percentage of cesarean sections
      was lower among foreign women than Italians women; c) with respect to average of
      all immigrant admitted for obstetrical pathologies, the largest group, according
      to the area of origin, was comprised of women from Africa and it was decided that
      the quality of obstetrical assistance received by this group should be verified.

PMID- 8545039
TI  - Cocaine during pregnancy: a critical review of the literature.
AB  - A number of epidemiological indices suggest that the use of cocaine in Italy is
      increasing, thus explaining the importance of scientific interest in this field.
      There is considerable disparity between the scientific papers published in the
      literature concerning the damaging effects on fetus and mother linked to the use
      of cocaine during pregnancy. The main problem consists of the method used to
      identify those patients using cocaine. These methods are burdened by a high level
      of false negatives: subjects who often use a variety of active pharmacological
      substances are identified and the methods are not always suitable for classifying
      subjects according to useful clinical parameters. This is reflected in the poor
      quality of data concerning the epidemiology and clinical aspects of cocaine abuse
      during pregnancy. A careful selection of the best scientific papers published in
      the literature shows that the effects on the maternal organism are slight,
      whereas those on the fetus are more severe. Compared to controls, the use of
      cocaine is associated with a high percentage of cardiac malformations, preterm
      delivery, low birth weight and minor anomalies of the nervous system. Results
      relating to sudden neonatal death are discordant. This paper shows that the use
      of cocaine is often underestimated both in epidemiological terms and from the
      fetal point of view. This behaviour is linked to the belief that the effects of
      cocaine are benign.

PMID- 8545040
TI  - [A rare cause of uterine rupture during pregnancy].

PMID- 8545041
TI  - [Diabetic nephropathy and pregnancy].
AB  - Diabetes mellitus (or type 1) is a long-lasting disease (even twenty years or
      more) which causes kidney disease and, in the event of pregnancy, it can make
      differential diagnostic difficult even fort the most expert clinician. Metabolic
      changes caused by this type of diabetes (e.g., hypoglycemia, hyperglycemia,
      ketoacidosis) and their difficult compensation can often lead to the onset of
      eclampsia or convulsion. The diagnostic suspicion of diabetes is supported by the
      finding of proteinuria, edema and hypertension that are strictly correlated with
      the evolution of diabetic disease and sometimes exist prior to pregnancy. This
      cas report focuses on the diagnostic importance of clotting tests, especially in
      clarifying diagnostic doubts.

PMID- 8545042
TI  - [Medico-legal controversies in obstetrics and gynecology: an important current
      problem].
AB  - Medicolegal controversies have recently grown to alarming proportions, also in
      relation to the increasingly widespread use of insurance policies and the
      doctor's compulsory need to obtain the patient's informed consent. According to
      current juridical attitudes, a surgeon carrying out surgery without the patient's
      consent may be guilty of severe damage or premeditated manslaughter in the event
      that the patient is injured. Some aspects of the relating to obstetrics
      gynecology which have been the subject of recent medico-legal controversies are
      discussed in this paper. The authors underline the role played by the official
      expert and the need for the latter to be professionally up-to-date on the subject
      which he is called upon to judge.

PMID- 8545043
TI  - CA3 neuronal degeneration follows chronic entorhinal cortex lesions.
AB  - Entorhinal cortex lesions are a common experimental paradigm to study memory
      function and neural plasticity after hippocampal deafferentation. The long term
      consequences of such lesions are of particular interest both in the context of
      these models and because pathological changes of Alzheimer's disease destroy
      entorhinal cortex projection neurons. We used stereological counting techniques
      to assess the structural integrity of the hippocampal formation 0.5-28 months
      after entorhinal lesion in the rhesus monkey. Surprisingly, 18-28 months after
      lesion the number of CA3 neurons was decreased by 57%, while neuron numbers in
      other subfields did not change. These results suggest that delayed transsynaptic
      neural degeneration can occur long after brain injury.

PMID- 8545044
TI  - A keratan sulfate proteoglycan marks the boundaries in the cortical barrel fields
      of the adult rat.
AB  - The present study uses the monoclonal antibody TED 15 to examine the distribution
      of a keratan sulfate proteoglycan, ABAKAN, in the barrel field of the rat
      somatosensory cortex. At birth there is very little ABAKAN present in the
      somatosensory cortex. The levels of this proteoglycan increase during development
      until the highest levels are reached in the adult rat. Immunohistochemistry
      reveals that the TED 15 immunoreaction product marks the boundaries between
      cortical barrels. At postnatal day 7 (P7) the proteoglycan is localized
      specifically to the boundary regions. As the brain matures, the levels of ABAKAN
      increase in the barrel hollows and in the surrounding cortex; however the
      boundary regions maintain a higher level of expression even in the adult animal.
      The high levels of ABAKAN observed in the adult barrel fields indicate that
      unlike other boundary molecules this proteoglycan may be involved in maintaining
      the structure of the adult somatosensory cortex.

PMID- 8545045
TI  - Direct measurement of fast axonal transport rates in corticospinal axons of the
      adult rat.
AB  - The bi-directional movement of proteins from the soma to the axon terminal is
      called axonal transport. Fast anterograde transport moves organelles and membrane
      bound proteins distally. Fast transport rates were measured in corticospinal
      tract axons of male Sprague-Dawley rats by microinjection of tritiated proline
      into the sensorimotor cortex. Animals were killed after 3-5 h and the tract cut
      into 1 mm segments. A bimodal wave of radiolabeled proteins was evident, with the
      first peak at the spino-medullary junction and the second peak in cervical spinal
      segments. The fast transport rate was calculated at the leading edge of the
      distal wave, and found to be 303 +/- 44 mm/day.

PMID- 8545046
TI  - Extracellular gamma-aminobutyric acid in the substantia nigra reticulata measured
      by microdialysis in awake rats: effects of various stimulants.
AB  - The gamma-aminobutyric acid (GABA)-ergic system in the substantia nigra
      reticulata (SNR) was challenged by local infusion of various receptor-specific
      agents to obtain additional information on the physiological significance of
      extracellular GABA levels as measured by microdialysis in awake rats.
      Notwithstanding in vitro results, basal extracellular GABA levels were not
      affected by local infusion of the GABA-A agonist muscimol or by infusion of the
      GABA-B agonist baclofen. Upon a dopaminergic challenge, the D2 agonist LY 171555
      was equally ineffective, but the D1 agonist induced an increase in extracellular
      GABA levels, which persisted in the presence of tetrodotoxin (TTX). Using
      excitatory amino acids, kainic acid was ineffective in modulating GABA levels,
      whereas N-methyl-D-aspartate induced an increase in extracellular GABA levels,
      again persisting when co-infused with TTX. The functional significance of TTX
      independent changes in extracellular GABA levels is discussed.

PMID- 8545047
TI  - Localization and activation of glutamate receptors in unmyelinated axons of rat
      glabrous skin.
AB  - Immunohistochemical staining for the glutamate receptor subtypes N-methyl-D
      aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) results in a significant number of labeled unmyelinated
      axons in the glabrous skin of the rat hindpaw. Injection of glutamate into the
      rat hindpaw results in behavioral changes interpreted as mechanical allodynia and
      mechanical hyperalgesia. The anatomical findings provide a reasonable explanation
      for the action of the exogenous peripheral glutamate, namely that activation of
      these receptors leads to increased primary afferent activity in unmyelinated
      axons and thus to pain behaviors. AMPA receptors are frequently associated with
      small clear vesicles in the axoplasm of the unmyelinated axons, many of which
      have been previously shown to contain high concentrations of glutamate. This
      finding indicates that these might be autoreceptors and so glutamate itself might
      regulate certain types of peripheral impulse traffic. The presence of peripheral
      glutamate receptors associated with unmyelinated axons suggests the possibility
      that glutamate antagonists applied peripherally might prevent or attenuate some
      pain-related behaviors.

PMID- 8545048
TI  - Atrial natriuretic factor enhances norepinephrine uptake in circumventricular
      organs, locus coeruleus and nucleus tractus solitarii of the rat.
AB  - The effects of atrial natriuretic factor (ANF) on norepinephrine (NE) uptake in
      circumventricular organs (organum vasculosum lamina terminalis, organum
      subfornicale and area postrema), locus coeruleus and nucleus tractus solitarii
      were studied in the rat. Experiments were carried out in vitro using nuclei
      obtained according to the punch-out technique. Results showed that 100 nM ANF
      enhanced NE uptake in all nuclei studied. These results suggest that ANF may be
      indirectly related to the control of cardiocirculatory functions,
      hydroelectrolyte balance, neuroendocrine secretions, nutrient and metabolic
      homeostasis, through the modulation of noradrenergic neurotransmission at the
      neuronal presynaptic level.

PMID- 8545049
TI  - Expression of messenger RNA encoding a paraneoplastic cerebellar degeneration
      associated antigen in the rat hippocampus.
AB  - The PCD17 protein is a paraneoplastic cerebellar degeneration (PCD)-associated
      neural autoantigen which is recognized by autoantibodies in sera of PCD patients.
      The localization of the PCD17 mRNA was examined by in situ hybridization
      histochemistry using a PCD17 cRNA probe. In the cerebellum, the localization of
      the transcript was in agreement with the distribution of PCD17-immunoreactivity.
      On the other hand, intense hybridization signals were detected in most of cells
      in the hippocampus in which notable PCD17-immunoreactivity was undetected. These
      observations suggest that some negative translational or post-transcriptional
      mechanisms of the PCD17 mRNA may be involved in neurons of the hippocampus.

PMID- 8545050
TI  - Inverse correlation of acetylcholinesterase (AChE) activity with the presence of
      neurofilament inclusions in dorsal root ganglion neurons cultured in the presence
      of a reversible inhibitor of AChE.
AB  - We have previously shown that treatment of cultured dorsal root ganglion neurons
      (DRGN) with a highly specific, reversible acetylcholinesterase (AChE) inhibitor,
      BW284c51, retards neuritic outgrowth in a dose dependent manner and is
      accompanied by the presence of abnormal, perikaryal neurofilament (NF) inclusions
      in approximately 40% of the cells. Since subpopulations of DRGN have been
      classified according to their levels of AChE activity, we have combined
      immunocytochemical and enzyme histochemical techniques to investigate a possible
      correlation between AChE activity and the presence of NF inclusion formation. Our
      results show that after inhibitor treatment, cells with low levels of AChE
      activity have a greater percentage of inclusions, with nearly 75% of cells with
      undetectable levels of AChE activity containing inclusions. In contrast,
      inclusions were present in only 3.2% of cells with high levels of AChE activity.
      This inverse relationship between AChE activity and the presence of NF inclusions
      supports our previous observations that this enzyme may have extra-synaptic
      functions which could affect neuronal development and regeneration.

PMID- 8545051
TI  - Effect of somatostatin on the mass accumulation of inositol-1,4,5-trisphosphate
      in rat hypothalamus, striatum, frontoparietal cortex and hippocampus.
AB  - Somatostatin-14 (SS) significantly increased inositol-1,4,5-trisphosphate (IP3)
      accumulation in rat hypothalamic, striatal, frontoparietal cortical and
      hippocampal slices. However, this stimulation of IP3 accumulation by SS was
      highest in the frontoparietal cortex and hippocampus. The effect was already
      significant with 0.01 microM in the frontoparietal cortex (P < 0.05) and
      hippocampus (P < 0.05) and the maximal accumulation was evident with 0.1 microM
      SS, in all areas studied. A concentration of 1 microM SS, lacked this effect in
      hypothalamus and striatum. SS rapidly increased IP3 accumulation in all brain
      areas studied. This effect was maximal at 15 s of incubation and decreased
      subsequently. At 60 s incubation, levels were still elevated in frontoparietal
      cortex and hippocampus but had returned to basal values in hypothalamus and
      striatum. Somatostatin-28 (SS-28) and the SS analogues, D-Trp8-D-Cys14 and SMS
      201-995, also significantly stimulated IP3 accumulation although the effect of
      SMS 201-995 was greater than that of SS in the striatum in comparison with
      controls (P < 0.001 and P < 0.01, respectively). These results suggest that SS
      action at the hypothalamus, striatum, frontoparietal cortex and hippocampus is
      mediated at least in part by the accumulation of IP3, which may initiate
      intracellular processes responsible for some biological SS effects.

PMID- 8545052
TI  - Age related change in the vasoactive intestinal polypeptide-immunoreactive
      neurons in the cerebral cortex of aged rats.
AB  - Recent studies have explored certain changes in neurons containing neuropeptides
      with aging. However, until now, the degree of vasoactive intestinal polypeptide
      (VIP)-containing neuronal cell loss in the aged CNS has not yet been established
      with certainty, and available data are often contradictory. Changes in the VIP
      containing neurons with aging were demonstrated by immunocytochemisty. Major loss
      of VIP-immunoreactive neurons in the aged rat brain were observed in frontal
      cortex area 3, parietal cortex area 1, hindlimb area, temporal cortex area 1 and
      2, monocular part of occipital cortex area 1, occipital cortex area 2, and
      retrosplenial cortex. Frontal cortex area 1 and 2, parietal cortex area 2,
      forelimb area, binocular part of the occipital cortex area 1, and the dentate
      gyrus were moderately decreased. The axis of the VIP neurons in the aged group
      showed an irregular orientation tendency, especially in layers II and III. These
      results indicate the involvement of a neuronal system containing VIP in the aging
      brain, and provide the first morphological evidence for the loss of VIP neurons
      in the cerebral cortex of the aged rat.

PMID- 8545053
TI  - Arginine vasopressin stimulates 32P labeling of phosphoinositides in rat pineal
      gland.
AB  - The peptidergic innervation of the pineal gland contains arginine vasopressin
      (AVP) fibers. Since the site and molecular mechanism of AVP action on the pineal
      signal transduction has not yet been determined, we examined whether the inositol
      phosphate transduction system is involved. The phosphoinositide signaling system
      was studied by measuring metabolic turnover of phosphatidylinositol (PI),
      phosphatidylinositol phosphate (PIP) and phosphatidylinositol bisphosphate
      (PIP2), which reflects phosphoinositide cycle activation. AVP induced a
      significant increase in 32P labeling of PI, PIP and PIP2. The V1 receptor site(s)
      blocker for AVP abolished enhanced 32P labeling of PIP and PIP2. AVP was without
      effect on cAMP dependent phosphorylation. The data indicate that AVP activates
      the phosphoinositide signaling system via V1 receptors and is without effect on
      the cAMP system.

PMID- 8545054
TI  - Brain polyamine levels are altered in Alzheimer's disease.
AB  - Despite considerable evidence implicating polyamines in CNS function, little is
      known about the status of the polyamine system in normal or abnormal human brain.
      We measured the levels of the polyamines spermidine, spermine and their precursor
      putrescine, in cortical and subcortical areas of 12 patients with Alzheimer's
      disease (AD). As compared with the controls, mean levels of spermidine were
      markedly and significantly increased (70%) whereas putrescine levels were
      decreased (28%) in temporal cortex of the AD patients. No other statistically
      significant changes were observed with the exception of a mean 35% reduction in
      spermine concentration in occipital cortex. In view of the modulatory effects of
      polyamines on calcium flux and glutamate receptor function, our data suggest that
      abnormal polyamine system activity may be involved in the neurodegenerative
      processes occurring in brain of patients with AD.

PMID- 8545055
TI  - Neuroprotection after focal cerebral ischaemia in hyperglycaemic and diabetic
      rats.
AB  - The effects of acute hyperglycaemia and streptozotocin-induced diabetes on
      infarct size were measured 48 h after middle cerebral artery occlusion (MCAO) in
      Fischer 344 rats. Both hyperglycaemia (+46%) and diabetes (+68%) increased
      infarct volume when compared to normoglycaemic rats. Insulin-treated diabetic
      rats exhibited an infarct size similar to that observed in normoglycaemic rats.
      Neuroprotection has been difficult to demonstrate in pathological conditions that
      increase infarct volume such as chronic arterial hypertension. However,
      administration of the non-competitive NMDA antagonist, dizocilpine (MK-801),
      after MCAO, reduced the volume of ischaemic damage (by 33-48%) in all groups. The
      present findings indicate (a) that the detrimental effects of experimental
      diabetes on infarct volume are largely attributed to hyperglycaemia; and (b)
      dizocilpine was as neuroprotective in hyperglycaemia and diabetic conditions as
      in normoglycaemic rats.

PMID- 8545056
TI  - Involvement of 5-HT3 receptor in the pressure-induced increase in striatal and
      accumbens dopamine release and the occurrence of behavioral disorders in free
      moving rats.
AB  - Rats exposed to high pressure developed locomotor and motor activity (LMA) that
      correlated with an increase of DA release in both the nucleus accumbens and the
      caudate-putamen. We investigated the effects of the 5-HT3 receptor antagonist MDL
      72222 on these pressure-induced neurochemical and behavioral disorders. MDL 72222
      totally blocked the pressure-induced increase in accumbens DA release and the
      development of LMA, whereas it only reduced the increase in striatal DA release.
      This suggest that both LMA and the increase of DA release in the nucleus
      accumbens, but not in the caudate-putamen, could specifically result from a 5-HT3
      receptor activation in rats exposed to high pressure.

PMID- 8545057
TI  - Effects of pinealectomy and constant light exposure on day-night changes of
      melatonin binding sites in the goldfish brain.
AB  - Effects of pinealectomy and constant light exposure on day-night changes of
      melatonin binding sites in the goldfish brain were examined. The density and
      affinity of binding sites were higher at mid-day than at mid-night in sham
      pinealectomized goldfish under light-dark cycles. The rhythms disappeared after
      pinealectomy, or constant light exposure both of which abolish plasma melatonin
      rhythms. The effects of pinealectomy and constant light exposure were not
      additive. These results indicate that diel changes of melatonin binding sites in
      the goldfish brain are regulated by endogenous melatonin of pineal origin.

PMID- 8545058
TI  - Different effects of aluminum upon carbonic anhydrases and Na+/K+-ATPase
      activities in rat.
AB  - Aluminum (Al(III)) is a well established toxicant implicated as an etiological
      factor in several neuropathies. In this paper we report results regarding
      opposite effects produced by Al(III) on the activity of two enzymes utilized as
      models. While sodium-potassium ATP-ase (Na/K-ATPase) is strongly activated by
      Al(III) in a dose-effect dependent way, on the contrary, carbonic anhydrase (CA)
      is remarkably inhibited. The relevance of the metal speciation together with the
      enzymatic structural modification demonstrated by circular dichroism measurements
      could explain the observed modified enzymatic activities. In addition, a new
      experimental protocol for the preparation of Al(III) solutions at physiological
      pH useful in the standardization of Al(III) experimental toxicology is also
      proposed and discussed.

PMID- 8545059
TI  - Inhibitory effects of cholecystokinin on rat's geniculate activity can be blocked
      by GABA-antagonists.
AB  - Cholecystokinin applied iontophoretically as the sulfated octapeptide (CCK-8S) or
      as highly selective CCKA- and CCKB-agonists induced excitatory as well as
      inhibitory effects on dorsal lateral geniculate unit activity. Inhibitory effects
      of CCK could be abolished by administration of GABAergic antagonists, especially
      bicuculline. Therefore, interneurons seem to be largely excited by CCK, and in
      this way, they appear to mediate the inhibition of the discharge rate in
      geniculate relay cells induced by CCK.

PMID- 8545060
TI  - The effect of fatigue caused by electrical induction or voluntary contraction on
      Ia inhibition in human soleus muscle.
AB  - A comparison of the effect of fatigue caused by electrical induction or voluntary
      contraction on Ia inhibition in human soleus muscle was investigated in fourteen
      healthy male subjects. The Hoffmann reflex (H reflex) was employed to elucidate
      the contribution of fatigue induced contraction to the Ia inhibition. A
      statistically significant difference (P < 0.05) in H reflex amplitude between the
      intermittent stimulation at 15 Hz and voluntary contraction was observed. Our
      study suggested that Ia inhibition in human soleus muscle, caused by electrically
      induced or voluntary contraction, induced differences in the number of impulses
      in the group Ia fibers, between the two conditions.

PMID- 8545061
TI  - Effects of myosin light chain kinase inhibitors on delayed rectifier potassium
      current in bullfrog sympathetic neurons.
AB  - Actions of myosin light chain kinase inhibitors were tested on delayed rectifier
      potassium current (IK) in dissociated bullfrog sympathetic neurons. A microbial
      product, wortmannin (10 microM, extracellularly) and a synthetic peptide, SM-1
      (20 microM, intracellularly) caused approximately 35 mV hyperpolarizing shift of
      the inactivation curve. Substitution of ATP (1.15 mM) in the pipette solution
      with 5'-adenylylimidodiphosphate mimicked the actions of wortmannin and SM-1.
      Results suggest that phosphorylation of myosin may modulate kinetics for the
      inactivation of IK.

PMID- 8545062
TI  - Immunohistochemical localization of endothelial nitric oxide synthase in vessels
      of the dura mater of the Sprague-Dawley rat.
AB  - Nitric oxide (NO) and the dura mater are implicated in the pathogenesis of
      vascular headache. Many studies have demonstrated the participation of NO in
      headache; however, few studies have identified NO in the dura mater. In this
      study, nine Sprague-Dawley rats were examined with immunohistochemistry using two
      different endothelial nitric oxide synthase (eNOS) monoclonal antibodies, H32 and
      ECNOS. eNOS was successfully localized to the endothelium of the middle meningeal
      artery. To the best of our knowledge, this is the first study to report NOS
      immunopositive endothelial cells in the blood vessels of the rat dura mater. The
      authors propose that NO plays an active role in dural vasodilation, contributing
      to the pathogenesis of vascular headache; in the future, NO inhibitors could
      serve as pharmacological agents to treat vascular headache.

PMID- 8545063
TI  - Evoked potentials distinguish between nouns and verbs.
AB  - Electrocortical correlates of the processing of nouns and verbs were recorded in
      32 healthy individuals performing lexical decisions. Analyses of EEG data
      recorded through 29 channels revealed different topographies of cortical activity
      evoked by nouns and verbs. Differences were most pronounced at recording sites
      over the frontal lobes. The stronger motor associations elicited by verbs as
      measured pre-experimentally seem to be responsible for the topographical
      differences of event related brain potentials to verbs and nouns. In agreement
      with recent evidence from brain-damaged subjects, these results provide evidence
      that (1) nouns and verbs have distinct neural generators and that (2) these
      generators involve areas outside the classical language regions of the brain.

PMID- 8545064
TI  - Lamina VII neurons are rhythmically active during locomotor-like activity in the
      neonatal rat spinal cord.
AB  - The midsagittally-sectioned lumbar spinal cord with thoracic segments intact
      retains the capacity for locomotor-like activity. Intracellular recordings were
      used to characterize the activity and concurrently label lumbar neurons in lamina
      VII, an area previously implicated in the generation of locomotion. Sharp
      electrodes were shown to preferentially impale larger neurons. These neurons
      undergo rhythmic voltage oscillations, presumably synaptically driven, during
      locomotor-like activity induced by bath application of N-methyl-D-aspartate and 5
      hydroxytryptamine. This supports the hypothesis that synaptic activity recruits
      neurons in lamina VII that are associated with locomotor behavior.

PMID- 8545065
TI  - Professional liability.

PMID- 8545066
TI  - Prostaglandin injection therapy for men with a reasonable level of sexual
      activity.
AB  - A one-year experience with small doses of prostaglandin suggests that the
      improvement in erectile quality may be so significant as to erase any reluctance
      of men to supplement their own normal erectile activity. Prostaglandin injection
      therapy showed quantitative and qualitative benefits.

PMID- 8545067
TI  - Cooperative activity among health care providers in New Jersey.
AB  - The New Jersey Legislature is considering legislation providing antitrust
      exemption for health care entities or professionals in order to encourage them to
      enter into joint ventures without the fear of antitrust prosecution. This
      legislation will promote better health care.

PMID- 8545068
TI  - Lessons learned from autopsies at a pediatric teaching hospital.
AB  - Twenty-six percent of pediatric patients had discrepant major diagnoses revealed
      at autopsy. A printed form used to document permission for autopsies improved the
      autopsy rate. No variables were found to predict the success rate for obtaining
      autopsies.

PMID- 8545069
TI  - Is it time to consider a liability shield?
AB  - New Jersey physicians would do well to consider some form of legally protected
      structure rather than an unprotected partnership or sole proprietorship. Despite
      the advent of the new LLC and LLP structures, the entity of choice may still be
      the professional association.

PMID- 8545070
TI  - Radiology/pathology conference at Robert Wood Johnson Medical School.
AB  - A healthy female was noted to have an enlarging mass in the suprasternal fossa.
      The clinical diagnosis of post-traumatic arteriovenous fistula led to diagnostic
      arteriography and radiologic evaluation.

PMID- 8545071
TI  - Molecular biological approach to the circadian clock mechanism.
AB  - Many circadian phenomena have been described in a diverse range of species, from
      single cellular organisms to higher species of plants and animals. From several
      lines of evidence from Drosophila and Neurospora, the oscillation of the
      circadian clock seems to involve cycling gene expression. Although a great deal
      of information concerning the anatomy, neurophysiology and neurochemistry of
      circadian pacemakers has been obtained over the last decade, molecular and
      cellular approaches to this problem have only just begun. I will summarize recent
      progress of the molecular biological approach to the circadian clock mechanism.
      Finally, the importance of transcription factors to envision the common mechanism
      of circadian clock in the diverged species will be discussed considering with the
      existence of a hypothetical 'Time Box'.

PMID- 8545072
TI  - A quantitative study of the effects of prenatal X-irradiation on the development
      of cerebral cortex in rats.
AB  - Pregnant rats were exposed to a single whole body X-irradiation on day 15 of
      gestation at a dose of 1.0 Gy. The offspring showed microcephaly at 7 weeks of
      age. Their body weight, brain weight, cortical thickness and the numerical
      density of neurons and synapses in the somatosensory and visual cortex were
      examined. Significant decreases in cortical thickness in both somatosensory (25%)
      and visual (16%) cortex were observed. However, there were no significant changes
      in the numerical density of neurons and synapses, nor in synapse-to-neuron ratios
      in both cortical regions between control and X-irradiated groups. These results
      suggest that prenatal X-irradiation can decrease the number of neurons, and the
      neurons which survive X-irradiation proliferate and elaborate connections in a
      normal fashion. This is in contrast to the animals exposed to ochratoxin A, in
      which numerical density of neurons in the somatosensory cortex is increased, with
      normal numerical density of synapses, resulting in low synapse-to-neuron ratios.
      The discrepancy in the synapse-to-neuron ratios between the X-irradiation and
      ochratoxin A-treatment might derive from a different effect on the developing
      neurons.

PMID- 8545073
TI  - Relation of the enhancement of entorhinal tetanic responses by 50-Hz amygdala
      stimulation to the progression of kindling in the rat.
AB  - We recorded entorhinal tetanic responses to 50-Hz kindling stimulations applied
      at the amygdala in conscious rats, which produced facilitation and depression
      during the train pulses, in order to analyze the relationship of the changes in
      the tetanic responses to the development of both after-discharges (ADs) and
      behavioral seizures. Facilitation was always produced in the earlier tetanic
      responses and was followed by depression which reached a quasi-steady level in
      the later tetanic responses during each kindling stimulation. To estimate the
      changes in magnitude of the excitatory synaptic activation in the tetanic
      responses, with reference to the development of seizure stages, tetanic responses
      which produced the same behavioral seizure stage in each rat were averaged and
      the area between the negative (excitatory) potentials and the baseline of the
      averaged tetanic response was measured in terms of mV x ms. Magnitudes of the
      averaged negative components were significantly enhanced with an increase in the
      order of seizure stages in eight rats (P < 0.01). In addition, the mean magnitude
      of the averaged negative components had a linear correlation (r = 0.95, P < 0.05)
      with the mean AD duration with reference to the order of seizure stages in the
      eight rats. The magnitude of the positive (inhibitory) component in the averaged
      tetanic responses was also measured and found to decrease with an increase in the
      seizure stages (P < 0.01). The magnitude of the negative component in the test
      responses to single (0.3 Hz) stimuli just before kindling stimulations also
      increased with an increase in the order of seizure stages, indicating long term
      potentiation of the responses by kindling stimulations. We concluded from the
      results that the enhancement of facilitation of the excitatory synaptic
      activation and the reduction of the inhibitory synaptic activation in entorhinal
      tetanic responses by 50-Hz amygdala kindling stimulation is involved in the
      electrophysiological source of the progression of kindling epilepsy.

PMID- 8545074
TI  - Prostaglandin D2 modulates sleep-related and noradrenaline-induced activity of
      preoptic and basal forebrain neurons in the rat.
AB  - Prostaglandin D2 (PGD2) was applied by pressure through a multibarrel
      micropipette to sleep-related neurons in the preoptic and neighboring basal
      forebrain area in head-restrained unanesthetized rats. During wakefulness, PGD2
      excited six of 13 sleep-active neurons, inhibited seven of 13 waking-active
      neurons, and did not affect the remaining neurons. During slow-wave sleep (SWS),
      however, PGD2 excited only three of 17 sleep-active neurons and inhibited two of
      13 waking-active neurons. State-indifferent neurons, which lacked activity
      related to the sleep-waking state, were insensitive to PGD2 irrespective of
      wakefulness (n = 24) and SWS (n = 40). These results suggest that PGD2 promotes
      sleep by exciting sleep-active neurons and by inhibiting waking-active neurons.
      Furthermore, continuous administration of PGD2 attenuated activity changes
      associated with wakefulness of five sleep-active and three waking-active neurons
      tested. Because we had suggested the involvement of preoptic noradrenaline (NA)
      in arousal, we examined possible modulatory effects of PGD2 on NA-induced neuron
      responses. PGD2 attenuated NA-induced inhibitory responses in four of six sleep
      active neurons and in one of 10 state-indifferent neurons. PGD2 also attenuated
      NA-induced excitation in four waking-active neurons tested. Accordingly, the
      modulatory action of PGD2 on sleep-related neurons is important in the mechanism
      of sleep.

PMID- 8545075
TI  - Somatotopy of monkey premotor cortex examined with microstimulation.
AB  - We reinvestigated the organization of the premotor cortex (PM) using
      intracortical microstimulation. Movements of forelimb, hindlimb, and orofacial
      structures were evoked from broad regions of PM that appeared to be contiguous
      with other motor areas. There were two principal findings: (1) the somatotopy of
      PM lies roughly parallel to that of the primary motor cortex (MI). Forelimb
      movements were evoked from sites deep in the caudal bank of the arcuate sulcus
      and throughout the adjacent cortex bounded by a face representation (laterally)
      and a hindlimb representation (medially and caudally); (2) unlike the MI, the PM
      forelimb representation overlaps significantly with its own face representation.
      PM hindlimb movement sites overlap only slightly with PM forelimb sites, in a
      manner similar to the MI. There was no obvious boundary between PM, MI, or
      supplementary motor area hindlimb representations. The present findings are
      discussed in relation to recently identified subdivisions of the PM.

PMID- 8545076
TI  - Responses of the medial prefrontal cortex to stimulation of the amygdala in the
      rat: a study with laminar field potential recording.
AB  - Responses generated in the prelimbic-infralimbic cortices (areas 32 and 25) by
      stimulation of the basolateral amygdala were studied by means of laminar field
      potential recordings. Based on the analysis of wave forms and depth potential
      profiles of the responses, three constituent responses were identified: (1) a
      surface-positive potential with a short onset latency (mean, 4.5 ms) and a long
      duration (ca. 70 ms) that reversed the polarity at a depth of 400 microns; (2) a
      surface-positive potential with a mean onset latency of 15 ms and a duration of
      20 ms that reversed to a negative potential at a depth of 300 microns; and (3) a
      long-latency (ca. 20 ms) superficial-negative potential that reversed to a
      positive potential at depths below 400 microns. Lesion experiments ruled out the
      possibility that impulse traffic via the thalamic mediodorsal nucleus (MD)
      contributed to the responses. Amygdala stimulation also produced responses in the
      insular cortex, but they did not contaminate the responses in the mesial cortex.
      It is proposed that impulses originating from the amygdala provide excitation for
      cortical pyramidal cells at a short latency at deeper layers, but with
      considerable delays at upper and superficial layers, in the medial prefrontal
      cortex (mPFC).

PMID- 8545077
TI  - Brief exposure to hypoxia induces bFGF mRNA and protein and protects rat cortical
      neurons from prolonged hypoxic stress.
AB  - We examined the hypoxic tolerance phenomenon in vitro. Brief exposure to hypoxia
      induced the production of basic fibroblast growth factor (bFGF) mRNA and protein
      in rat cortical neurons and protected them from hypoxic injury. Cortical neurons
      were cultured from 18th-day rat embryos in a serum-free medium and subjected to
      brief (4 h) and/or prolonged (24 h) hypoxia. Neuronal damage was assessed by
      quantifying lactate dehydrogenase (LDH) activity in the medium. After brief
      hypoxia, LDH release was identical to that of the controls, whereas prolonged
      hypoxia caused a significant increase in LDH release, indicating neuronal death.
      However, if brief hypoxia was applied 2 days prior to the prolonged hypoxia, no
      increase in LDH release was observed. The bFGF mRNA expression was assessed with
      Northern blot and protein immunoreactivity with Western blot analysis. The brief
      period of hypoxia caused a 2.5-fold increase in bFGF mRNA and considerable bFGF
      protein expression 1 day later, but prolonged hypoxia caused increase in the
      expression of bFGF mRNA at 2 days and no protein expression until 3 days after
      the start of the hypoxia. When cells were subjected to prolonged hypoxia 2 days
      after brief hypoxia, however, no increase in bFGF mRNA was observed, while bFGF
      protein was expressed continuously. We also observed that exogenously applied
      bFGF reduced neuronal injury produced by prolonged hypoxia. The results obtained
      with this model suggest that brief hypoxia induces bFGF protein and thus
      tolerance to subsequent lethal hypoxia. Basic FGF might play a role as a
      tolerance-associated factor in this process. Thus, an in vitro model is useful
      for assessing the response of cortical neurons to hypoxic stress and for
      researching new factors related to ischemic tolerance.

PMID- 8545078
TI  - Ca(2+)-dependent Cl- current at the presynaptic terminals of goldfish retinal
      bipolar cells.
AB  - In ON-type bipolar cells dissociated from the goldfish retina, a slowly declining
      inward current (Itail) was observed after the termination of depolarizing voltage
      step commands, during which a Ca2+ current was elicited. The properties of Itail
      were investigated under the whole-cell voltage clamp. Introduction of the
      membrane permeant Ca2+ chelator, BAPTA/AM, into the cell suppressed Itail,
      indicating that Itail was activated by the increase of intracellular free Ca2+
      concentration ([Ca2+]i). The major component of Itail was identified as the
      Ca(2+)-dependent Cl- current (ICl(Ca)), since the reversal potential of Itail was
      almost identical to the Cl- equilibrium potential at various extracellular Cl-
      concentrations ([Cl-]o). The contribution of the Na+/Ca2+ exchanger current to
      Itail was very small. ICl(Ca) was partially suppressed by 4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid (SITS) when it was locally applied to
      the axon terminal but not to the cell body region, suggesting that Ca(2+)
      dependent Cl- channels were localized to the axon terminal. The relationship
      between the peak amplitude of ICl(Ca) and the amount of charge carried by the
      Ca2+ current was almost linear at levels less than ca. 50 pC, but became
      saturated at a higher Ca2+ charge.

PMID- 8545079
TI  - Changes in the central and peripheral serotonergic system in rats exposed to
      water-immersion restrained stress and nicotine administration.
AB  - The effects of water-immersion restraint stress (WS) on chronically nicotine
      administered rats were studied in the blood and various regions of the brain.
      Serotonin (5-HT) levels increased in the hypothalamus, hippocampus, cortex and
      cerebellum following the administration of nicotine. 5-HT levels increased in all
      the brain regions following stress. Nicotine decreased stress-induced increased
      levels of 5-HT in the hippocampus and cerebellum. Nicotine administration alone
      increased 5-hydroxyindole acetic acid (5-HIAA) levels in the hippocampus and
      cerebellum. Stress alone also increased 5-HIAA levels in all the brain regions.
      In the cortex, 5-HT and 5-HIAA levels further increased following the
      administration of a combination of stress and nicotine compared to rats given
      stress alone. In the blood as well as in all the brain regions, except the
      cerebellum, stress or nicotine administration did not affect tryptophan levels.
      Stress given to nicotine-administered rats resulted in a decrease in tryptophan
      levels in the blood and plasma. Although 5-HT and 5-HIAA levels were not
      influenced by stress and/or nicotine administration, the 5-HIAA/5-HT ratio
      increased in the blood and plasma of rats administered with nicotine and exposed
      to stress. The effects of nicotine on the serotonergic system depend upon the
      kind of stress given together with the organs and brain regions involved.

PMID- 8545080
TI  - Morphine-induced prolactin release precedes a down-regulation of prolactin
      receptors in the male rat choroid plexus and hypothalamus.
AB  - In previous studies we provided evidence for changes in prolactin (PRL) receptor
      levels in the male rat brain after continuously infusing morphine using
      subcutaneously implanted miniosmotic pumps. In this work we have studied the
      binding of PRL in the male rat brain following morphine administration by both
      subcutaneous (s.c.) and intracerebroventricular (i.c.v.) injections. The binding
      in the choroid plexus and the hypothalamus was measured using iodinated ovine PRL
      (oPRL) as a radiolabel. The results indicated that the density of the PRL-binding
      sites in the hypothalamus and the choroid plexus were significantly decreased 4 h
      and 24 h after s.c. injections, and also 30 min and 4 h after i.c.v. injections.
      However, no decrease in PRL-binding was observed 15 min after i.c.v. injection of
      morphine. The plasma levels of PRL were measured by radioimmunoassay (RIA) and
      were found to be significantly increased after 30 min and 4 h in all treated
      animals. Following i.c.v. injection a significant increase in plasma PRL was
      observed after just 15 min. It was suggested that the down-regulation in PRL
      binding to some extent at least resulted from receptor overstimulation caused by
      the morphine-induced elevation in the concentrations of the endogenous hormone.

PMID- 8545081
TI  - Water deprivation in the rat induces nitric oxide synthase (NOS) gene expression
      in the hypothalamic paraventricular and supraoptic nuclei.
AB  - We examined the effects of water deprivation on nitric oxide synthase (NOS) gene
      expression in the rat hypothalamic paraventricular (PVN) and supraoptic nuclei
      (SON), using in situ hybridization histochemistry. Dehydration caused a
      significant increase in NOS gene transcripts in the PVN and SON but not in the
      subfornical organ (SFO). The results suggest that dehydration has a major effect
      on the NOS gene expression in the PVN and SON.

PMID- 8545082
TI  - Functional brain block preparation of the rat auditory cortex.
AB  - To maintain neural functions in brain block preparations of the rat auditory
      cortex in vitro, a pressurized oxygenated medium was injected into the blocks.
      Distribution of indigo carmine contained in the injection medium indicated that a
      columnar region of 1-2 mm in diameter was homogeneously perfused from the white
      matter to the pial surface. Stimulation of cortical layers just above the white
      matter produced supragranular field potentials of two negative peaks. They
      represented antidromic and postsynaptic activities, of which only the latter was
      blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The depth
      profile and temperature-dependency of field potentials in the blocks were very
      similar to those recorded in usual slice preparations. The responses in blocks
      were recorded stably for several hours. The functional brain block preparation
      may be a useful tool for analyses of neocortical neural networks in vitro.

PMID- 8545083
TI  - Point/counterpoint: I. A viable fetus presenting as a breech in labor needs a
      cesarean delivery.

PMID- 8545084
TI  - Point/counterpoint: II. Management of a full-term fetus presenting by the breech.

PMID- 8545085
TI  - Early complications of abdominal and vaginal hysterectomy.
AB  - In 1982, the Collaborative Review of Sterilization (CREST) study was published,
      reviewing the complications accompanying and following both abdominal and vaginal
      hysterectomy. This review was undertaken to see how these rates have changed in
      the ensuing years. All large series of abdominal and vaginal hysterectomy
      complications published subsequent to the CREST study were reviewed.
      Additionally, other studies that focused on specific complications were reviewed.
      It is concluded that the following changes related to hysterectomy morbidity have
      occurred since the publication of the CREST study: 1) the use of blood
      transfusion has diminished due to concern regarding human immunodeficiency virus
      contamination; 2) the rate of urinary tract infection has decreased primarily due
      to routine use of prophylactic antibiotics; and 3) inadvertent injury to the
      bladder has been noted more frequently at a rate of 1 to 2 percent. A
      particularly important category of complication is "unintended major surgical
      procedures which accompany or follow hysterectomy." This has been shown to occur
      at a rate of approximately 4 percent on general gynecology services. Finally,
      risk factors that add to the morbidity of hysterectomy are discussed.

PMID- 8545086
TI  - Benefits and risks of episiotomy: a review of the English-language literature
      since 1980. Part I.
AB  - The professional literature on the benefits and risks of episiotomy was last
      reviewed critically in 1983, encompassing material published through 1980. This
      paper reviews the evidence accumulated since then. (Part II follows in this
      issue.) It is concluded that episiotomies prevent anterior perineal lacerations
      (which carry minimal morbidity), but fail to accomplish any of the other maternal
      or fetal benefits traditionally ascribed, including prevention of perineal damage
      and its sequelae, prevention of pelvic floor relaxation and its sequelae, and
      protection of the newborn from either intracranial hemorrhage or intrapartum
      asphyxia. In the process of affording this one small advantage, the incision
      substantially increases maternal blood loss, the average depth of posterior
      perineal injury, the risk of anal sphincter damage and its attendant long-term
      morbidity (at least for midline episiotomy), the risk of improper perineal wound
      healing, and the amount of pain in the first several postpartum days.

PMID- 8545087
TI  - Benefits and risks of episiotomy: a review of the English-language literature
      since 1980. Part II.
AB  - Mediolateral and, to a lesser degree, midline episiotomies substantially increase
      the amount of blood loss at delivery; in fact, simple avoidance of episiotomy may
      be the most powerful means the delivery attendant has to prevent excessive
      intrapartum hemorrhage. The long-term morbidity of the anal sphincter damage
      induced by episiotomy, particularly midline, has generally been underestimated in
      both its frequency and severity. Other potential fetal and maternal complications
      of episiotomies, although rare, are numerous and serious. The overall degree of
      risk that accompanies this procedure could only be justified by a clear and
      overriding benefit, which, as discussed under "Benefits" earlier in this review,
      does not appear to exist.

PMID- 8545088
TI  - Study of the correlation between average values of optic disc parameters and
      their measurement variability using stereovideographic digital analysis.
AB  - Purpose of our study was to find whether there is a correlation between average
      values of optic nerve head parameters and their coefficient of variation for
      repeated measurements. Disc stereo video images were taken with Topcon Imagenet
      (IS100) and analyzed with the Optic Disc Analysis program. Eleven normal and 9
      glaucomatous eyes were selected. A significant correlation was found for
      horizontal cup/disc ratio (r = -0.037, p = 0.037) and disc area (r = 0.776, p =
      0.027) in intra-observer intra-image repeated measurements. Vertical, horizontal
      and average cup/disc ratios (r = -0.81, r = -0.74, r = -0.78 p < 0.05) showed a
      significant correlation for intra-observer inter-image repeated measurements. For
      inter-observer intra-image measurements, a significant correlation was present
      for average cup/disc ratio (r = -0.64, p = 0.043). Our data show that
      bidimensional semiquantitative parameters in use for optic nerve head assessment,
      analyzed by computerized stereovideography, have an intrinsic measurement
      variability. The variability is significantly related to the value of the
      measured parameter only when their reference points are determined manually by
      the operator.

PMID- 8545089
TI  - MRI in Graves orbitopathy: recognition of enlarged muscles and prediction of
      steroid response.
AB  - The purpose of this study is to compare MRI to CT in the recognition of Graves
      orbitopathy and to compare MRI to clinical examination in the prediction of
      steroid response. Sixteen patients with dysthyroid orbitopathy (21 orbits) were
      examined by CT and MRI; muscle enlargement was measured by ultrasonography.
      Sensitivity in recognizing enlarged muscles was 85.4% for CT and 61.2% for MRI;
      CT recognized all affected orbits but 1, while MRI failed in 4 cases. Clinical
      inflammatory signs (p = 0.17) were more reliable predictors of steroid response
      than muscular T2 hyperintensity on MRI (p = 0.64). In a patient where
      histological examination documented edematous changes, MRI failed to reveal
      edema. MRI adds no morphologic information to CT; moreover, T2 intensity is less
      specific than clinical examination in documenting active disease and forecasting
      therapeutic outcome.

PMID- 8545090
TI  - Oscillatory potentials in subjects with treated hypertension.
AB  - Oscillatory potentials of the ERG proved to be a sensitive indicator even in mild
      disturbances of retinal circulation, such as the first stage of hypertensive
      retinopathy (WHO classification). Oscillatory indexes (OIs) and blood pressure
      levels of 24 hypertensive patients in stage 1 of the WHO classification, who
      underwent an antihypertensive therapy for the first time, were considered. The
      patients were retested after a mean period 8 months. a strict inverse correlation
      was found between OIs and blood pressure levels.

PMID- 8545091
TI  - [Iridocorneal angle pigmentation and intraocular pressure: gonioscopic appearance
      of a large number of individuals].
AB  - The relationship between iridocorneal angle pigmentation and intraocular pressure
      has not been adequately explained. 2,730 subjects without any pathological
      changes in the anterior segment (aged 15-96 years) were examined gonioscopically
      to establish a classification of age-dependent superficial and deep pigmentation
      and their combinations. Accurate gonioscopy may reveal the relationship between
      some types of pigmentation and glaucoma.

PMID- 8545092
TI  - Contrast sensitivity evaluation in eyes predisposed to age-related macular
      degeneration and presenting normal visual acuity.
AB  - In order to test the validity of contrast sensitivity (CS) measurements in the
      early detection of visual impairment in age-related macular degeneration (AMD),
      we have evaluated the findings of CS in patients with drusen and normal visual
      acuity (17 eyes), as well as in the contralateral 'healthy' eye of patients with
      AMD (14 eyes). We also tried to estimate the validity of CS measurements in the
      prognosis of neovascular macular degeneration. The CS findings were evaluated in
      comparison to the findings of CS measurements in age-matched controls (32 eyes).
      CS loss is a constant finding in eyes with drusen and normal visual acuity. CS
      loss is more important at the middle range and high spatial frequencies. CS loss
      and degree of CS loss are not prognostic indicators of neovascular macular
      degeneration.

PMID- 8545093
TI  - Relationship between intraocular pressure and age in the exfoliation syndrome.
AB  - We examined the presence or absence of exfoliative material and measured the
      intraocular pressure (IOP) of 220 residents of a nursing home. The prevalence of
      the exfoliation syndrome increased with age and the IOP of persons with the
      exfoliation syndrome was higher than that of persons without the syndrome. In
      eyes with the exfoliation syndrome, the IOP had a tendency to decrease with
      increasing age. Aging had little influence on IOP in eyes without the exfoliation
      syndrome. There were significant differences between the two groups with regard
      to the effects of aging on IOP.

PMID- 8545094
TI  - Clinical features of retinal detachment in the elderly.
AB  - We conducted a retrospective study of 636 eyes (624 patients, aged 65 years or
      more) to identify the clinical features of nontraumatic retinal detachment in the
      elderly. The incidence of retinal detachment due to a macular hole in our series
      (21%) was much higher than those described in previous reports, suggesting a
      racial difference between Japanese and Caucasian patients. Tractional tear was
      seen more commonly in patients of less advanced age. In addition, in our series
      of elderly patients, we demonstrated (1) a preponderance of retinal breaks in the
      upper temporal quadrant, (2) a high incidence of aphakic retinal detachment, (3)
      a preponderance of females to be affected and (4) broad detachment of the retina
      that involved the macula.

PMID- 8545095
TI  - Direct sub-Tenon's ocular anesthesia for strabismus surgery.
AB  - We assessed the safety and effectiveness of sub-Tenon's anesthesia, a local
      anesthesia, for strabismus surgery. For 15 surgeries, we used anesthesia by sub
      Tenon's infusion, followed by direct infusion through a transconjunctival route
      with a local anesthetic agent. We found the procedure was simple, it minimized
      complications compared with other techniques and was effective in achieving rapid
      anesthesia. With the ocular movement remaining, we checked eye position by the
      alternative cover-uncover test at the end of surgery. We obtained good eye
      position for all patients. This method leads to good results for strabismus
      surgery.

PMID- 8545096
TI  - Inhibition of experimental proliferative vitreoretinopathy in rabbits by suramin.
AB  - Proliferative vitreoretinopathy (PVR) is the most common cause for failure of
      retinal reattachment surgery. In a search for better pharmacologic treatment of
      PVR, we investigated the effect of intravenous injections of suramin on an
      experimental rabbit model of PVR. PVR was induced in rabbits by intravitreal
      injection of autologous fibroblasts. The experimental group (7 eyes) received
      intravenous injections of suramin (100 mg/kg body weight) every 3 days for 15
      days, beginning 3 days before fibroblast injection. The control group (5 eyes)
      was treated similarly but received intravenous saline solution in place of
      suramin. A third group (4 eyes) received suramin according to the protocol above
      but did not receive intravitreal fibroblasts. The animals were examined by
      indirect ophthalmoscopy every 3 days and were sacrificed 14 days after the
      injection of fibroblasts. The serum levels of suramin were evaluated by high
      performance liquid chromatography. The PVR was classified as stages I-V, based
      upon clinical findings. PVR developed in both experimental and control animals
      but was less severe in those treated with suramin. On day 14, the average stage
      of PVR in the control group was 3.8; in the suramin-treated group, however, the
      average stage was 2.4, which was significantly less than in the control group (p
      < 0.02). None of the rabbits in the third group showed pathologic changes. Serum
      levels of suramin were maintained at an average of 280.2 micrograms/ml and no
      apparent toxicity was found in the retina by histologic study.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8545097
TI  - Association of peripapillary scars with lesions characteristic of multiple
      evanescent white-dot syndrome.
AB  - Multiple evanescent white-dot syndrome, acute idiopathic blind-spot enlargement
      syndrome and multifocal choroiditis (pseudo-ocular histoplasmosis syndrome) are
      fundus diseases of unknown etiology. A single etiological agent or group of
      similar agents is thought to be responsible for these relatively rare
      manifestations. A 35-year-old male with associated symptoms of enlargement of the
      blind spot, evanescent white-dot syndrome and presumed ocular histoplasmosis is
      described. The association of these highly differentiated fundus abnormalities
      strengthens the hypothesis of an etiological or pathological linkage within
      phenotypically variable clinical forms.

PMID- 8545098
TI  - Concurrent acute angle-closure glaucoma, choroidal detachment and exudative
      retinal detachment in a patient with spontaneous carotid cavernous fistula.
AB  - A 61-year-old woman had proptosis, pulsation of the globe, orbital bruit and
      epibulbar congestion in the left eye. The cavernous sinus appeared enlarged by
      computed tomography. No trauma was noted. Despite the lack of carotid
      angiographic findings, the patient was diagnosed as having spontaneous carotid
      cavernous fistula. No surgery was performed. At the age of 67 years, the patient
      complained of pain in the left eye. Acute angle-closure glaucoma, choroidal
      detachment and exudative retinal detachment were concurrently found in the left
      eye. An ocular pulse on the tonography reading in the left eye was larger than in
      the right eye. Concurrent acute angle-closure glaucoma, choroidal detachment and
      exudative retinal detachment with carotid cavernous fistula, as found in our
      patient, may be rare.

PMID- 8545099
TI  - Bilateral acute angle-closure glaucoma after dexfenfluramine treatment.
AB  - We report the case of a patient with narrow angles who had an attack of bilateral
      acute angle-closure glaucoma precipitated by dexfenfluramine, a serotoninergic
      drug developed for appetite suppression. Although the exact mechanism remains
      uncertain, the pupillary block observed in our case may be the result of the
      serotoninergic or indirect parasympatholytic properties of the drug on the iris
      sphincter muscle. Serotonergic psychoactive drugs should be prescribed cautiously
      in patients with known narrow angles and should be monitored by an
      ophthalmologist.

PMID- 8545100
TI  - Down gaze palsy due to periaqueductal lesion diagnosed by magnetic resonance
      imaging.
AB  - Selective paralysis of downward gaze is known to be rare. There are 6 cases
      reported in the literature based on neuropathologic and anatomical studies. We
      report a 60-year-old diabetic and hypertensive patient with isolated down gaze
      palsy. Computed tomography failed to show the lesion in the periaqueductal
      region, and the diagnosis was made by Magnetic resonance imaging. The case
      presented is the only one still surviving.

PMID- 8545101
TI  - Imaging techniques in the diagnosis of lacrimal sac diverticulum.
AB  - Lacrimal sac diverticulum is a rare condition characterized by a cystic structure
      communicating with the sac. This abnormality may be directly demonstrated by
      dacryocystography only in a few cases; in the remaining cases, preoperative
      diagnosis may be arduous. We report 3 cases of lacrimal sac diverticulum. In all
      patients, symptoms were represented by a palpable mass in the lacrimal sac
      region, associated with permanent (case 1) or episodic (cases 2 and 3) epiphora.
      In the first case, CT-dacryocystography revealed an apparently solid mass causing
      inferior lacrimal obstruction, and ultrasonography disclosed a cystic space, not
      communicating with the sac. At surgery, a sac diverticulum was identified and
      excised. In the second patient, CT showed a homogeneous rounded mass, whereas a
      cystic character was revealed by T1-weighted MRI. Dacryocystography showed a
      lateral impression on the lateral wall of the sac. Ultrasonography revealed a
      cystic space communicating with the lacrimal sac. In the third case,
      ultrasonography demonstrated a diverticulum. CT is often unable to discriminate
      tumors from lacrimal cysts, both showing a parenchymal density. MRI can
      differentiate lacrimal cystic spaces from solid tumors by T1 intensity and by
      demonstration of their walls, but it is nonspecific for diverticula. Only
      dacryocystography and B-scan ultrasonography can reveal the narrow communication
      between the sac and the diverticulum. Observation is the recommended management
      for asymptomatic cases.

PMID- 8545102
TI  - High prevalence of RET rearrangement in thyroid tumors of children from Belarus
      after the Chernobyl reactor accident.
AB  - RET rearrangement was studied in papillary thyroid carcinomas (PTC) of children
      exposed to radioactive fallout in Belarus after the Chernobyl accident. To detect
      RET rearrangement in small tissue samples from thyroidectomy specimen (12 PTC of
      children; 2 PTC and 1 follicular carcinoma of adults; non-tumorous thyroid tissue
      of 4 children and 4 adults as controls), a RT-multiplex PCR was developed using
      primers suited to amplify fragments in different quantities depending on the
      presence or absence of RET rearrangements in the tissues. The type of
      rearrangement was determined by RT-PCR and direct sequencing using primers for
      ret/PTC1, 2 and 3. Two-thirds of the papillary thyroid carcinomas of the children
      revealed a RET rearrangement, with ret/PTC3 being more frequent by a factor of 3
      than ret/PTC1. ret/PTC2 was not detected. All RET rearrangement-positive tumors
      had lymph node metastasis while half of the tumors with wild-type cRET had not.
      More than half of the cases with ret/PTC3 expressed not only the ELE/RET
      transcript as expected, but also the RET/ELE transcript. Intrachromosomal
      rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10
      is a very frequent event in thyroid cancer of children of the Chernobyl
      contaminated zone of Belarus.

PMID- 8545103
TI  - Functional hierarchy of c-kit and c-fms in intramarrow production of CFU-M.
AB  - Whereas the molecular natures of M-CSF/CSF-1 and its receptor c-fms are well
      characterized, its actual role in the intramarrow hematopoiesis remains obscure.
      This is because disruption of this signaling pathway results in the osteopetrosis
      mouse that lacks the bone cavity for hematopoiesis. To elucidate the role of c
      fms in intramarrow hematopoiesis, we produced an antagonistic monoclonal antibody
      to murine c-fms and investigated its expression and function in the normal bone
      marrow. c-fms+ cells were detected both in mature and immature hematopoietic
      cells. Morphologically, c-kit+c-fms-, c-kit+c-fms+ and c-kit-c-fms+ cells were
      medium sized blasts, large promyelocytes with azurophilic granules and mature
      monocytes respectively. CFU-M was 10-fold more enriched in the c-kit+c-fms- than
      c-kit+c-fms+ fraction. Moreover, injection of the anti c-fms antibody had no
      effect on the production of CFU-M in the bone marrow, while anti-c-kit mAb could
      deplete them. As c-kit+c-fms+ cells were readily generated in the culture of c
      kit+c-fms- cells, most of the CFU-M in the bone marrow are, in fact, c-fms- cells
      that differentiate into c-fms+ upon culture. These observations indicate a clear
      functional hierarchy of c-kit and c-fms in the bone marrow. Namely, c-kit plays
      the primary role in the production and maintenance of CFU-M, while c-fms, though
      it co-expressed with c-kit and functions as the growth receptor for M-CSF in the
      culture, has only a minimum role in the proliferation of c-fms+ cells in the bone
      marrow.

PMID- 8545104
TI  - Subtraction hybridization identifies a novel melanoma differentiation associated
      gene, mda-7, modulated during human melanoma differentiation, growth and
      progression.
AB  - Cultured human melanoma cells lose proliferative capacity and terminally
      differentiate after treatment with the combination of recombinant human
      fibroblast interferon (IFN-beta) and mezerein (MEZ). Subtraction hybridization of
      cDNA libraries prepared from actively proliferating human H0-1 melanoma cells
      from cDNA libraries produced from H0-1 cells treated with IFN-beta + MEZ
      identifies a novel melanoma differentiation-associated (mda) cDNA, mda-7, that
      displays elevated expression in differentiation inducer-treated H0-1 cells. mda-7
      encodes a novel protein of 206 amino acids with a predicted size of 23.8 kDa. The
      level of mda-7 mRNA is elevated in actively proliferating normal human
      melanocytes versus primary and metastatic human melanomas. In the Matrigel
      assisted melanoma progression model, mda-7 expression decreases in early vertical
      growth phase primary human melanoma cells selected for autonomous or enhanced
      tumor formation in nude mice. Treatment of human melanomas with IFN-beta + MEZ,
      and to a lesser extent with MEZ, results in growth suppression and induced or
      enhanced mda-7 expression. Immunoprecipitation analyses using peptide-derived
      rabbit polyclonal antibodies detect increases in mda-7 protein, and a higher
      molecular weight protein of approximately 90 to 100 kDa, in MEZ and IFN-beta +
      MEZ treated H0-1 cells. mda-7 is a highly conserved gene with an homologous
      sequence in the genome of yeast. Transfection of mda-7 expression constructs into
      H0-1 and C8161 human melanoma cells reduces growth and inhibits colony formation.
      These results confirm that mda-7 has antiproliferative properties in human
      melanoma cells and in this context may contribute to terminal cell
      differentiation. The mda-7 gene may also function as a negative regulator of
      melanoma progression.

PMID- 8545105
TI  - Regulation of Myc and Mad during epidermal differentiation and HPV-associated
      tumorigenesis.
AB  - c-Myc and Mad each form heterodimers with Max that bind the same E-box related
      DNA sequences. Whereas Myc:Max complexes activate transcription and promote cell
      proliferation and transformation, Mad:Max complexes repress transcription and
      block c-Myc-mediated cell transformation. Here we examine these antagonistic
      transcription factors during epithelial differentiation and neoplastic
      progression. During differentiation of primary human keratinocytes, Mad is
      rapidly induced and c-Myc is downregulated, resulting in a switch from c-Myc:Max
      to Mad:Max heterodimers. In normal epidermis and colonic mucosa c-myc expression
      is restricted to proliferating cell layers, while mad expression is restricted to
      differentiating cell layers. Using HPV18 transformed keratinocytes that vary in
      their ability to differentiate in organotypic cultures, we find that Mad
      induction occurs only in those cells that retain a differentiation response. In
      the epidermis of transgenic mice in which expression of the HPV16 E6 and E7
      oncogenes are targeted to basal keratinocytes, neoplastic progression occurs and
      is marked by an expansion of c-myc expressing basal-like cells. Expression of mad
      is found only in growth-arrested differentiating cells on the outer edges of
      preneoplastic lesions. The squamous cell carcinomas that arise evidence a
      variable number of sites within the tumor masses where mad expression and
      morphological differentiation coincide; increasing malignancy correlates with
      loss of both mad and capability to differentiate. These results indicate that c
      Myc and Mad expression are tightly coupled to the transition from proliferation
      to differentiation of epithelial cells and that restriction of Mad expression may
      be associated with loss of normal differentiation capability and with
      tumorigenesis.

PMID- 8545106
TI  - Loss of imprinting of IGF2 in Ewing's sarcoma.
AB  - Insulin-like Growth Factor 2 (IGF2) has recently been demonstrated to be
      maternally imprinted in both mice and humans. We previously reported loss of
      imprinting (LOI) of IGF2 in rhabdomyosarcoma (RMS) where IGF2 has been shown to
      act as an autocrine growth factor and play an important role in pathogenesis.
      Since IGF2 does not appear to play a role in the pathogenesis of Ewing's sarcoma,
      we sought to determine whether normal IGF2 imprinting was maintained in these
      tumors. Of 32 Ewing's tumors examined for imprinting of IGF2, 10 were informative
      heterozygotes and three of these expressed IGF2 biallelically. Furthermore, all
      three tumors with LOI and five of seven tumors with normal imprinting transcribed
      IGF2 mRNA at lower levels while relatively higher levels of IGF2 expression was
      observed in the remaining two tumors with normal imprinting. These data
      demonstrate altered imprinting of IGF2 occurs in some Ewing's sarcomas. However,
      LOI of IGF2 in Ewing's sarcoma was not associated with increased expression of
      IGF2 mRNA, suggesting that LOI may not be involved in the regulation of IGF2
      expression and may be related to genetic or epigenetic abnormalities in tumors
      independent of IGF2 expression.

PMID- 8545107
TI  - Stimulation of c-Jun activity by CBP: c-Jun residues Ser63/73 are required for
      CBP induced stimulation in vivo and CBP binding in vitro.
AB  - The CBP protein mediates PKA induced transcription by binding to the PKA
      phosphorylated activation domain of CREB. Here we show that CBP also stimulates
      the activity of both c-Jun and v-Jun in vivo. The CREB binding domain of CBP is
      sufficient to contact to c-Jun in vitro. When this domain of CBP is linked to the
      activation domain of VP16 and expressed in vivo it stimulates c-Jun dependent
      transcription. Deletion analysis of c-Jun indicate that the CBP binding site is
      within the N-terminal activation domain. Loss of binding to CBP in vitro
      correlates with severely reduced transactivation capacity in vivo. Mutation of
      Ser63/73 in c-Jun, or the corresponding position in v-Jun (Ser36/46) leads to
      reduced binding to CBP in vitro and abolishes augmentation of transcription in
      vivo. These data are consistent with a mechanism by which CBP acts as a co
      activator protein for Jun dependent transcription by interacting with the Jun N
      terminal activation domain.

PMID- 8545108
TI  - Translational upregulation of the c-myc oncogene in Bloom's syndrome cell lines.
AB  - Previous studies have shown a constitutive increase in the levels of c-myc
      protein in cell lines derived from patients with the cancer-prone disorder
      Bloom's Syndrome (BS). We report here that this overexpression results from a
      specific increase in the translation of the c-myc mRNA and is not the result of
      either a chromosomal translocation involving the c-myc locus or an amplification
      of this gene. We also did not detect any increase in the stability of the c-myc
      protein or any significant increases in the levels of c-myc mRNA expressed in BS
      cells compared to control cell lines. Overall, there is a 39-80% increase in the
      association of the c-myc mRNA with polysomes in BS cell lines. Since, in some
      cases, overexpression of the c-myc protein has been shown to increase levels of
      the translation initiation factors eIF-4E and eIF-2 alpha, which may themselves
      play a role in malignant conversion, we have also examined the levels of these
      proteins in BS cells and found them to be either comparable or lower than those
      in control cell lines. These data suggest that if c-myc does contribute to the
      cancer predisposition phenotype in BS then it does not appear to act via an eIF
      4E and eIF-2 alpha mediated pathway.

PMID- 8545109
TI  - The SH2 domain of Shc suppresses EGF-induced mitogenesis in a dominant negative
      manner.
AB  - Recently, we have shown that an EGF-R-mutant lacking the autophosphorylation
      sites phosphorylates Shc and retains mitogenic activity. In this report, we have
      shown that in these cells, in response to EGF, Ras is fully activated with
      formation of the tyrosine-phosphorylated Shc-Grb2-mSOS complex without the
      receptor. This pointed out the importance of Shc in EGF-induced Ras activation.
      To investigate the mechanism of tyrosine phosphorylation of Shc by EGF-R, we
      carried out in vitro kinase assays using immunoprecipitated EGF-R and bacterially
      expressed Shc proteins as substrates. The EGF-R phosphorylated Shc, but not the
      Shc SH2 mutant, lacking binding ability for phosphotyrosine. This suggests that
      intact Shc SH2 is essential for the full-length Shc to become phosphorylated,
      probably by inducing a conformational change in Shc. Thus a Shc SH2 peptide may
      inhibit competitively Shc phosphorylation. We microinjected the Shc SH2 domain
      into NIH3T3 cells overexpressing the EGF-R. Microinjected Shc SH2 greatly
      suppressed EGF-induced DNA synthesis. But microinjection of neither the Shc SH2
      mutant nor PLC-gamma 1 SH2 had any effect. This suppressing effect was rescued by
      comicroinjection of the full-length Shc, suggesting Shc SH2 specifically
      suppressed the Shc pathway. Thus we concluded Shc phosphorylation is crucial,
      whereas receptor autophosphorylation is dispensable, in EGF-induced mitogenesis.

PMID- 8545110
TI  - The transforming oncoproteins determine the mechanism by which p53 suppresses
      cell transformation: pRb-mediated growth arrest or apoptosis.
AB  - To investigate the mechanisms by which p53 suppresses cell transformation, we
      used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a
      proteins, and an activated ras protein (EJ-ras), to examine different pathways of
      transformation for their susceptibility to suppression by p53: While p53 can
      suppress transformation by various oncoproteins, we have shown that it is unable
      to suppress the transformation of rat embryo fibroblasts (REFs) by LTag.
      Interestingly, the function of LTag which enables it to overcome the
      antiproliferative effects of p53 is not the binding and inactivation of p53, but
      the binding and inactivation of the pRb family of proteins. This observation
      indicates that pRb mediates a suppressive effect of p53 on cell transformation.
      We have also observed that in contrast to LTag, both E1a and EJ-ras cause
      transformation-related events which are susceptible to suppression by p53.
      Further studies have revealed that cells expressing E1a are susceptible to p53
      mediated apoptosis, while cells expressing EJ-ras are susceptible to p53-induced
      growth inhibition. We therefore propose that p53 suppresses transformation either
      by arresting cell growth (mediated by pRb in late G1) or by inducing apoptosis,
      with the mechanism being determined by the transforming oncoprotein(s).

PMID- 8545111
TI  - Increased cell-substratum adhesion, and decreased gelatinase secretion and cell
      growth, induced by E-cadherin transfection of human colon carcinoma cells.
AB  - Metastasis of colon carcinomas is assumed to be caused by multiple steps, which
      include a loss of cell adhesion that results in the release of carcinoma cells
      from the original tumor tissue. A human colon carcinoma cell line COKFu was
      established from a poorly differentiated metastatic adenocarcinoma without cell
      cell adhesion and without expression of E-cadherin mRNA and protein. This cell
      line was co-transfected with mouse E-cadherin cDNA in an expression vector and a
      neomycin-resistant gene. The parental carcinoma cells had a spindle shape and
      were scattered, whereas the transfected cells, which expressed exogenous E
      cadherin gene, showed a more compact shape with strong cell-cell adhesion and
      with increased adhesiveness to collagen gel. These cells showed a significantly
      low anchorage independency (2-7%) and decreased invasiveness (30%) compared to
      the parental cells. Growth rate of transfectants was decreased both in vitro and
      in the subcutis of nude mice, with decreased lymphnode metastasis in the case of
      intravenous injection. It was additionally found that activity of 62 kd
      gelatinase, secreted from parental cells, was lost or decreased in E-cadherin
      transfected cells. These results suggest that E-cadherin is not only involved in
      the cell-cell adhesion of colon carcinomas, it also has a wider effect, including
      cell-substratum adhesion and the regulation of proteinase secretion from the
      cells, resulting in partial suppression of invasiveness and tumorigenic growth.

PMID- 8545112
TI  - Isolation and characterisation of a uniquely regulated threonine, tyrosine
      phosphatase (TYP 1) which inactivates ERK2 and p54jnk.
AB  - The recent discovery of the vaccinia virus protein phosphatase VH1, and its
      mammalian counterparts has highlighted a novel subfamily of protein tyrosine
      phosphatases that exhibit dual specificity toward phosphotyrosine- and
      phosphoserine/threonine-residues. We have identified further members of this
      subfamily. The characterisation of one clone in particular, which we have named
      threonine-tyrosine phosphatase 1 (TYP 1), encodes a protein homologous to CL100,
      but differs dramatically in its regulation. TYP 1 is not expressed in human
      fibroblasts unlike other CL100-like genes. Furthermore, northern analysis has
      demonstrated that following mitogenic stimulation of squamous cells, induction of
      TYP 1 mRNA reaches its maximal levels after four hours, in contrast to the
      immediate early CL100-like genes. Both TYP 1 and CL100 mRNAs are induced upon TGF
      beta treatment of squamous cell lines sensitive to the growth factors
      antiproliferative effects. When TYP 1 is transfected into COS-1 cells, the gene
      product inhibits both ERK2 and p54 MAP kinase subfamilies. In addition, we show
      that purified TYP 1 protein efficiently inactivates recombinant ERK2 in vitro by
      the concomitant dephosphorylation of both its phosphothreonine and -tyrosine
      residues. TYP 1 encodes a nuclear protein, which when expressed in COS cells is
      stabilised by EGF treatment.

PMID- 8545113
TI  - Transcriptional induction of the PML growth suppressor gene by interferons is
      mediated through an ISRE and a GAS element.
AB  - PML is a nuclear matrix protein with growth suppressing properties, whose
      expression is deregulated during oncogenesis. Moreover, in the t(15;17)
      translocation of acute promyelocytic leukaemia (APL), PML fusion to the retinoic
      acid receptor alpha (RAR alpha) is the likely molecular basis of leukaemogenesis.
      Here we show that interferons (IFNs) alpha, beta, and gamma upregulate PML mRNA
      expression. Analysis of 5' genomic sequences of the PML gene revealed an IFN
      alpha/-beta stimulated response element (ISRE) and an IFN-gamma activation site
      (GAS) in the untranslated first exon. Binding of IFN signal transducers and
      activators of transcription (STATs) was demonstrated to be weak for the PML GAS,
      but strong for the PML ISRE which also seemed to contribute substantially to the
      IFN-gamma response. Thus, PML is a primary target gene of IFNs and would appear
      as a suitable candidate for mediating some of their antiproliferative effects.
      Abnormalities of PML structure, localisation or expression in human malignancy,
      constitute examples of how an IFN target gene may be altered in oncogenesis.

PMID- 8545114
TI  - Differential splicing of the mouse B-myb gene.
AB  - The myb gene family consists of three members, the c-myb proto-oncogene and two
      myb-related genes (A-myb and B-myb), all of which encode nuclear DNA-binding
      proteins. Unlike c-myb, which plays a critical role in hematopoietic cells, B-myb
      is expressed in a large spectrum of hematopoietic as well as non-hematopoietic
      cells and has been implicated in the control of cell proliferation. The isolation
      of B-myb cDNA clones from several species has shown that B-myb shares limited
      homology to the so-called exon 9A of the c-myb gene. This exon is involved in
      differential splicing as only a subfraction of c-myb mRNA contains exon 9A
      sequences. The presence in the B-myb cDNA of a sequence related to the exon 9A of
      c-myb has prompted us to investigate whether B-myb mRNA is also spliced
      differentially. We here show that B-myb mRNAs containing or lacking exon 9A
      related sequences are present in many cell types. In contrast to c-myb, where RNA
      containing the exon 9A constitutes only a minor mRNA fraction, B-myb RNA
      containing the exon 9A related sequences is the major mRNA form. The proteins
      encoded by the two B-myb mRNA species are unable to activate promoters to which
      they bind. Curiously, both B-myb proteins differ in their ability to activate the
      HSP70 promoter by a myb binding-site independent mechanism; B-myb protein
      containing exon 9A related aminoacid sequences activates the HSP70 promoter much
      more potently than the B-myb protein which lacks these sequences. Our results
      suggest that differential splicing may be a general feature of the members of the
      myb family and provide first evidence for functional differences of the splice
      variants.

PMID- 8545115
TI  - Compensatory apoptosis in response to SV40 large T antigen expression in the
      liver.
AB  - Transgenesis allows the in vivo determination of the effects of oncogene
      expression in normal tissues. In an attempt to understand the mechanism
      underlying liver transformation, we have previously created transgenic mice
      carrying the SV40 early gene sequences, which developed hepatocarcinoma in a
      reproducible way. In the present study, we show that constant expression of the
      transgene was directly correlated to an abnormally increased hepatocyte
      proliferation, even at the adult stage. We further demonstrate in this model that
      the preneoplastic stage of hepatocarcinoma is characterized by marked ploidy
      alterations as early as 1 month, including the emergence of aneuploid and
      hyperpolyploid cells, and the persistence of an important diploid cell
      population. We show that this elevated proliferation is early and transiently
      counterbalanced by a mechanism of apoptosis, which maintains liver homeostasis.
      The disappearance of this programmed cell death response effective during
      preneoplasia might signal the commitment of the liver to neoplasia.

PMID- 8545116
TI  - Sequential molecular genetic changes in lung cancer development.
AB  - Epithelial tumours develop through a sequence of pre-invasive lesions of
      increasing disarray driven by underlying somatic genetic changes. We have studied
      the occurrence of the two most common somatic genetic changes associated with
      lung cancer in a series of premalignant bronchial lesions representing different
      stages in lung tumorigenesis. We present evidence that allele loss on chromosome
      3 precedes damage to the p53 gene. Damage to chromosome 3 itself appears to be
      sequential in that the pattern of allele loss seen in dysplasia is often much
      more discrete than in invasive tumours. This implies that preneoplastic lesions
      may be a useful source of material for deletion mapping studies aimed at
      localising the position of tumour suppressor genes. We illustrate this by the
      comparison of an interstitial deletion described in this study with a homozygous
      deletion we have described previously, which has resulted in a better definition
      of the localisation of a tumour suppressor gene believed to be involved in lung
      cancer development.

PMID- 8545117
TI  - Over-expression of transfected N-myc oncogene in human SKNSH neuroblastoma cells
      down-regulates expression of beta 1 integrin subunit.
AB  - Amplification of the N-myc oncogene is associated with progression of
      neuroblastoma in humans. Previous studies indicated that neuroblastoma cell lines
      which are amplified for the N-myc gene and over-express N-myc exhibit enhanced
      tumorigenic properties when injected into athymic nude mice. In addition,
      neuroblastoma cells which over-express N-myc (IMR32 cells) expressed little or no
      beta 1, alpha 2, or alpha 3 integrin subunits, as compared with cells which do
      not express N-myc (SKNSH cells). In order to probe the possible relationship
      between N-myc and beta 1 integrin gene expressions more directly, transfection
      experiments were performed in which an N-myc cDNA (on the episomal expression
      vector pREP4; high-level constitutive expression is driven by an RSV-LTR
      promoter) was introduced into SKNSH cells. Expression of N-myc produced
      significant morphological alterations in transfected cells; one subpopulation of
      cells remained spread on tissue culture substrata, while a second subpopulation
      became rounded and grew as multi-cellular aggregates. Spread (attached) cells
      expressed low levels of N-myc and high levels of beta 1 integrin, while rounded
      (loose) cells expressed relatively high levels of N-myc and low levels of beta 1
      integrin. Maintenance of transfected cells in higher concentrations of selective
      agent produced a higher proportion of loose cells, which expressed even greater
      amounts of N-myc and even less beta 1 integrin; a similar effect was observed in
      attached cells. Interestingly, loose cell populations expressed elevated levels
      of the neural cell adhesion molecule [NCAM]. The results presented here infer
      that N-myc regulates the expression of the beta 1 integrin and NCAM cell-surface
      receptors responsible for cell:extracellular cellular matrix interaction and
      possibly cell:cell adhesion.

PMID- 8545118
TI  - Overexpression of human p21waf1/cip1 arrests the growth of chicken embryo
      fibroblasts transformed by individual oncogenes.
AB  - In normal cells, cell growth and division is controlled by the interplay between
      proto-oncogenes and tumor suppressor genes. Cancer cells usually have both
      activated an oncogene and have lost a functional tumor suppressor gene. High
      level expression of a tumor suppressor, p53, can block the growth of cancer
      cells. waf1/cip1 is transactivated by the tumor suppressor p53 and the
      p21waf1/cip1 protein is itself a suppressor of cell growth. To test the effect of
      growth suppression genes on the growth of cells transformed by individual
      oncogenes, we have used replication-competent retroviral vectors to induce high
      level expression of p53 and p21waf1/cip1. Overexpression of p21waf1/cip1 arrests
      the growth of chicken embryo fibroblasts (CEF) transformed by v-Src, tf-Ras, c
      Mos and c-Myc. These data suggest that p21waf1/cip1 might be a useful tool in
      gene therapy for human cancer.

PMID- 8545119
TI  - Overexpression of the Sky receptor tyrosine kinase at the cell surface or in the
      cytoplasm results in ligand-independent activation.
AB  - Most receptor tyrosine kinases are activated by dimerization induced by their
      cognate ligands. Protein S, an abundant serum protein previously shown to be a
      potent anticoagulation factor, has been proposed to be a ligand for the Sky
      tyrosine kinase (Stitt et al., 1995). Here we show that Sky, when expressed to
      high levels, is tyrosine phosphorylated even in the absence of a ligand.
      Furthermore, a version of Sky (termed Sky delta SS) engineered to be
      overexpressed in the cytoplasm and thus in a ligand-free environement, can
      function as a dimeric tyrosine kinase. Sky delta SS can transform RatB1a
      fibroblasts and thus retains all the properties of the full-length Sky kinase.
      These data suggest that Sky, when overexpressed either at the cell surface or in
      the cytoplasm, is competent to form dimers even in the absence of its ligand. We
      also demonstrate that an isoform of Sky, originally reported as Brt and here
      termed Sky Isoform I, resides in the cytoplasm. Therefore, the activities of Sky
      delta SS we describe may reflect those of the naturally occurring Isoform I.

PMID- 8545120
TI  - The proto-oncogene RON is involved in development of epithelial, bone and neuro
      endocrine tissues.
AB  - We previously showed that the proto-oncogene RON encodes the tyrosine kinase
      receptor for Macrophage Stimulating Protein (MSP), originally isolated as a
      chemotactic factor for peritoneal macrophages. To elucidate the biological role
      of MSP we studied the expression of the Ron receptor in vivo, and the response to
      the factor in vitro. RON specific transcripts were detectable in mouse liver from
      early embryonal life (day 12.5 p.c.) through adult life. Adrenal gland, spinal
      ganglia, skin, lung and--unexpectedly--ossification centers of developing
      mandible, clavicle and ribs were also positive at later stages (day 13.5-16.5
      p.c.). From day 17.5 RON was expressed in the gut epithelium and in a specific
      area of the central nervous system, corresponding to the nucleus of the
      hypoglossus. In adult mouse tissues RON transcripts were observed in brain,
      adrenal glands, gastro-intestinal tract, testis and kidney. Epithelial,
      osteoclast-like and neuroendocrine cells express the Ron receptor and respond to
      MSP in vitro. In the neuroendocrine PC12 cell line, while NGF induced growth
      arrest and morphological differentiation, MSP behaved as a strong mitogen. These
      findings show that the Ron receptor and its ligand are involved in the
      development of epithelial tissues, bones, and neuroendocrine derivatives driving
      cells towards the proliferation program.

PMID- 8545121
TI  - Regulation of urokinase-type plasminogen activator expression by the v-mos
      oncogene.
AB  - We undertook a study to determine if the serine-threonine kinase-encoding v-mos
      oncogene regulated the expression of the urokinase-type plasminogen activator. An
      expression vector encoding v-mos, but not a kinase-inactive mutant, stimulated
      urokinase promoter activity in CAT assays employing a squamous cell carcinoma
      cell line. The induction of urokinase promoter activity by v-mos was mediated, in
      part, via an increased AP-1 activity since (a) mutation of 2 AP-1 binding sites
      (at -1967 and -1885), or the co-expression of a transactivation domain-lacking c
      jun mutant reduced the induction of the urokinase promoter by v-mos and (b)
      expression of v-mos increased the activity of a CAT reporter driven by three AP-1
      tandem repeats. The stimulation of the urokinase promoter by v-mos was partially
      countered by co-expression of an ERK1/ERK2-inactivating phosphatase. Western
      blotting and zymographic analysis indicated that v-mos-transformed NIH3T3 cells
      (MSV NIH-3T3) secreted more urokinase compared with NIH3T3 cells and this was
      associated with a higher level of activated ERK1 and ERK2. Expression of a
      catalytically-inactive MAPKK mutant reduced the activity of a urokinase promoter
      driven CAT reporter in the MSV NIH-3T3 cells. In conclusion, the data herein
      indicate that urokinase expression is regulated by v-mos through a MAPKK
      dependent signaling pathway.

PMID- 8545122
TI  - The epidermal growth factor receptor is covalently linked to ubiquitin.
AB  - Incubation of cultured human fibroblasts with epidermal growth factor (EGF)
      causes a proliferative response that is mediated by the binding of the growth
      factor to specific cell surface receptors. One event that occurs rapidly
      following EGF binding is the covalent modification of the EGF receptor (EGF-R) by
      phosphorylation on Ser, Thr, and Tyr residues. Here we report the identification
      of ubiquitination as a second form of EGF-stimulated covalent modification of the
      receptor. The LGF receptor was not ubiquitinated in serum-starved cells. However,
      treatment with EGF caused a rapid increase in EGF-R ubiquitination. In contrast,
      no EGF-stimulated ubiquitination was found in experiments using cells that
      express a mutant tyrosine kinase-negative EGF-R. Similarly, ubiquitination of the
      EGF-R was not observed at 4 degrees C or if the cells are depleted of
      intracellular K+. Together, these data establish ubiquitination as a form of EGF
      stimulated covalent modification of the EGF-R.

PMID- 8545123
TI  - Induction of apoptosis by rho in NIH 3T3 cells requires two complementary
      signals. Ceramides function as a progression factor for apoptosis.
AB  - We have previously reported that rho genes, members of the ras superfamily, are
      tumorigenic when overexpressed in NIH 3T3 cells. As other known oncogenes, they
      also induce apoptosis after serum deprivation but not in the presence of growth
      factors. In the present study, we provide evidence that overexpression of the
      Aplysia Rho protein in NIH 3T3 cells induces the generation of
      phosphatidylcholine (PC)-derived second messengers as a result of activation of a
      PC-specific phospholipase D (PC-PLD) as previously reported for ras-transformed
      cells. In contrast, removal of serum in the Rho transfectants, but not in normal
      NIH 3T3 cells or cells transformed by the ras oncogene, induced the production of
      ceramides as a result of activation of an sphingomyelinase (SMase). Furthermore,
      the rho-expressing cells underwent apoptosis in the presence of serum when
      exogenous ceramides were added, and this process was accelerated if cells were
      treated with exogenous SMase. Thus, Rho proteins act as an initiation signal that
      is necessary but not sufficient for the induction of apoptosis in NIH 3T3 cells.
      We propose here that induction of apoptosis in NIH 3T3 cells requires two
      complementary signals: an initiation signal generated even in the presence of
      serum which 'primes' the cells, making them sensitive to a progression signal,
      triggered by serum removal, which we have identified as generation of ceramides.

PMID- 8545124
TI  - The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by
      AML1B.
AB  - The t(8;21) translocation, commonly found in acute myelogenous leukemia (AML),
      generates a fusion protein containing N-terminal AML1 and C-terminal ETO amino
      acids. The human AML1 gene encodes several related proteins that specifically
      bind to the sequence TGT/cGGT, located in the promoter regions of a variety of
      hematopoietic growth factor genes. To examine the abilities of the AML1B protein
      (which contains 479 amino acids), a shorter AML1A isoform (which contains amino
      acids 1-250), and the AML1/ETO fusion protein (which contains AML1A amino acids 1
      177) to stimulate transcription from the GM-CSF promoter, we performed co
      transfection experiments in T cells using a human GM-CSF promoter-CAT reporter
      gene plasmid and expression vectors that contain the cDNAs for one of the above
      proteins. Our data demonstrate that AML1B, but not AML1A or AML1/ETO
      transactivates the GM-CSF promoter, requiring the TGTGGT sequence contained
      between base pairs -68 and -53. Furthermore, we show that AML1/ETO, but not
      AML1A, inhibits the ability of AML1B to stimulate CAT expression. Electrophoretic
      mobility shift assays demonstrated the specific binding of AML1 proteins to the
      GM-CSF promoter TGTGGT sequence, which does not require GM-CSF sequences
      immediately upstream of this binding site. Our data support a role for AML1B as a
      transcriptional activator and establish that the AML1/ETO fusion protein can act
      as a dominant negative protein on the human GM-CSF promoter. Although AML1/ETO
      does not stimulate the transcription of GM-CSF, it may function by inhibiting the
      normal activity of AML1B in AML cells with the t(8;21) translocation.

PMID- 8545125
TI  - Mutations in the non-catalytic domains of Fyn and Fgr tyrosine kinases reveal
      differences in mechanisms of their regulation.
AB  - Non-catalytic domains of tyrosine kinases from the Src family are believed to be
      regulated intra- and intermolecularly through protein-protein interactions. We
      have deleted the SH2 and SH3 domains from Fyn and Fgr and have generated two
      point mutations in residues completely conserved in all members of the Src
      family. The dramatically different biological effects of these mutations suggest
      that non-catalytic domains regulate Src family kinase activities through
      distinctly different mechanisms.

PMID- 8545126
TI  - Differential expression of the fos and jun family members c-fos, fosB, Fra-1, Fra
      2, c-jun, junB and junD during human epidermal keratinocyte differentiation.
AB  - Activator protein 1 (AP1) family proteins have been implicated in the regulation
      of genes expressed in the epidermis. However, no comprehensive analysis of the
      expression patterns of the known AP1 family proteins in the human epidermis or
      any other terminally differentiating tissue has been performed. In the present
      study we describe the localization of c-fos, fosB, Fra-1, Fra-2, c-jun, junB and
      junD in the normal human epidermis. Each is expressed in specific epidermal
      layers. c-fos is localized in the nuclei of the upper spinous and granular layer
      cells. FosB is present in the nuclei in all layers. Fra-1 is absent from the
      basal layer, but is present in all other layers. Fra-2 is detected in all layers,
      but staining intensity is increased in the upper spinous layer. c-jun staining is
      limited to the granular layer, while junB and junD are present in all layers. The
      differentiation-dependent pattern of expression of the AP1 family members suggest
      an important role for these proteins in specifying the temporal and spatial
      pattern of gene expression during keratinocyte differentiation.

PMID- 8545127
TI  - The BTB/POZ domain targets the LAZ3/BCL6 oncoprotein to nuclear dots and mediates
      homomerisation in vivo.
AB  - The LAZ3/BCL6 gene was identified by its disruption in 3q27 translocations
      associated with diffuse large cell lymphomas. It is predicted to be a
      transcription factor as it contains six Kruppel-like Zinc finger motifs and a N
      terminal BTB/POZ domain, a protein/protein interaction interface that is widely
      conserved in Metazoans. Using two antisera raised against non overlapping regions
      of the predicted ORF, we demonstrate that the LAZ3/BCL6 protein appears as a
      close ca. 79 kDa doublet in B lymphoid cell lines with either a rearranged or a
      non rearranged LAZ3/BCL6 locus. By immunofluorescence experiments on transiently
      transfected COS-1 or NIH3T3 cells, we show that the LAZ3/BCL6 protein displays a
      punctuated nuclear localisation. This appears to rely on LAZ3/BCL6 proper folding
      and/or activities as it is impaired in a hormone reversible-fashion through
      fusion of LAZ3/BCL6 to the ligand-binding domain of the oestrogen receptor.
      Moreover, deletion of its BTB/POZ domain leads to the disappearance of the
      nuclear dots although the protein remains nuclear. In addition, by using the
      yeast two-hybrid system, we show that the LAZ3/BCL6 BTB/POZ domain homomerises in
      vivo. Thus, the LAZ3/BCL6 BTB/POZ domain has the capability to self-interact and
      target the protein to discrete nuclear substructures.

PMID- 8545128
TI  - The rearranged L-myc fusion gene (RLF) encodes a Zn-15 related zinc finger
      protein.
AB  - We have previously characterized intrachromosomal rearrangements at 1p32 fusing
      the first exon of the RLF gene with L-myc. Here we present the full-length cDNA
      sequence of the 6251 bp RLF mRNA. The predicted 1914 amino acid Rlf protein
      contains sixteen widely spaced zinc finger motifs, and is related to the Zn-15
      transcription factor. RLF is widely expressed in fetal and adult tissues,
      suggesting that it has a general role in transcriptional regulation. The zinc
      fingers are not contained in the 79 amino acid N-terminal region of RLF involved
      in the RLF-L-myc fusions, and the transforming ability of the RLF-L-myc and the
      normal L-myc proteins is indistinguishable. These findings suggest that the role
      of the rearrangements fusing RLF and L-myc is to deregulate the tightly
      controlled expression of the L-myc gene.

PMID- 8545129
TI  - Identification of a member of the TIS11 early response gene family at the
      insertion point of a DNA fragment containing a gene for the T-cell receptor beta
      chain in an acute T-cell leukemia.
AB  - In a previous paper (Proc. Natl. Acad. Sci. USA 84, 4264, 1987) we reported that
      a DNA fragment containing a gene for the T-cell receptor beta chain, which had
      been excised from chromosome 7q35 during D beta-J beta joining, was inserted into
      chromosome 6p21.3 in a patient with acute T-cell leukemia. We have since screened
      for genes in the vicinity of the insertion point and have identified a gene that
      is equivalent to the murine TIS11d gene, a member of TIS11 early response gene
      family, that contains unique Cysteine-Histidine motifs. The human TIS11d gene
      consists of two exons and encodes a polypeptide of 492 amino acids. The insertion
      of the DNA fragment observed in this patient is located at the carboxy-terminal
      portion of the TIS11d protein.

PMID- 8545130
TI  - Infrequent alteration of the c-myc gene in human glial tumours associated with
      increased numbers of c-myc positive cells.
AB  - Twenty five human glial tumours of different grades of malignancy were examined
      by Southern blotting and polymerase chain reaction (PCR) for alterations
      (rearrangements, amplification and deletions) in the c-myc gene. Number of c-myc
      positive cells per thousand cells were also counted in all the tumours after
      immunohistochemical staining for c-myc protein was done on fixed sections of the
      tumours. No tumours exhibited any amplification of the gene, as found by Southern
      blotting. One astrocytoma and one mixed glioma showed some rearrangements in the
      3' end of the gene, as detected by Southern blotting and hydridization. These two
      tumours had higher number of c-myc positive cells than in other tumours of the
      same histopathological groups. Deletion in the first promoter region, as
      determined by PCR, was seen in only one astrocytoma. However, the number of c-myc
      positive cells in that tumour did not show any deviation from that found in other
      astrocytomas. In light of present literature, it is speculated that the 3'
      rearrangements may be the cause of increased number of c-myc immunopositive cells
      in those tumours by disrupting the 3' end of the gene leading to increased c-myc
      mRNA stability. Such a mechanism may play a part in small subset of glial and
      possibly other tumours.

PMID- 8545131
TI  - Society victory nets in excess of $54 million for providers.

PMID- 8545132
TI  - What POs mean for PA physicians.

PMID- 8545133
TI  - KePRO project sheds light on anticoagulation in atrial fibrillation.

PMID- 8545134
TI  - Lovastatin during warfarin therapy resulting in bleeding.

PMID- 8545135
TI  - Finding good in a year of concerns.

PMID- 8545136
TI  - Policy needed on managed care referrals.

PMID- 8545137
TI  - Interrelationships of neurochemicals, estrogen, and recurring headache.
AB  - Recurring headache syndromes, such as migraine, are common problems for women
      throughout their adult lives. Headache symptoms often fluctuate over the years
      that they are present and, for most headache sufferers, these changes seem to
      occur randomly. For many women, however, chronic headache changes in predictable
      patterns in relation to alterations in hormonal states. Clinically, headache is
      often modified during menses, pregnancy, and menopause. Although sex hormones are
      changing with these clinical events, this paper will present the more important
      link between altered sex hormones and changes in neurochemicals believed to be
      responsible for recurring headache syndromes according to the neurobiological
      theory of migraine.

PMID- 8545138
TI  - Custom-made capsules and suppositories of methadone for patients on high-dose
      opioids for cancer pain.
AB  - In a prospective, open study, 37 advanced cancer patients in poor pain control
      receiving high doses of subcutaneous hydromorphone (mean daily dose: 276 +/- 163
      mg) were switched to methadone by use of custom-made capsules (21 patients) or
      suppositories (16 patients). The change in opioid took place over 6.5 +/- 3.6
      days (oral) and 3.2 +/- 2.7 days (rectal). The methadone/hydromorphone dose
      ratios were 1.2 +/- 1.3 and 3 +/- 2 for the oral and rectal routes, respectively
      (P = 0.03) as compared to an expected ratio of 5-7, based on single dose
      available data. Pain intensity (VAS 0-100 mm) and the number of extra doses of
      analgesic per day were 51 +/- 22 and 3.2 +/- 2.7 with hydromorphone, versus 34 +/
      21 (P < 0.001) and 2.1 +/- 1.9 (P = 0.03) with methadone, respectively. The
      total cost of treatment was Canadian $148 +/- 202 with methadone as compared to
      Canadian $2135 +/- 472 with hydromorphone (P < 0.001). Toxicity was limited to
      mild sedation in all patients and proctitis in 2 patients on suppositories (one
      of whom required discontinuation of methadone). Plasma levels obtained in 6
      patients on suppositories revealed large inter-individual variation in methadone
      level (ng/ml) to dose (mg/day) ratio (range: 0.8-8.5). Within individuals, the
      ratio remained constant over a range of doses. We conclude that a slow switch
      over to methadone is a safe, effective and low cost alternative in selected
      cancer patients receiving high doses of opioids for poor prognostic pain
      syndromes.

PMID- 8545139
TI  - Morphine and morphine metabolite concentrations in cerebrospinal fluid and plasma
      in cancer pain patients after slow-release oral morphine administration.
AB  - In 34 cancer patients treated with chronic slow-release oral morphine, plasma and
      cerebrospinal fluid (CSF) minimum steady-state concentrations of morphine (M),
      morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined by
      high-performance liquid chromatography (HPLC). Both plasma and CSF morphine, M3G
      and M6G, concentrations were linearly related to dose of morphine. At steady
      state, the mean +/- SEM CSF/plasma morphine concentration ratio was 0.8 +/- 0.1.
      In plasma and CSF, the mean steady-state concentrations of M3G and M6G
      substantially exceeded those of morphine where the mean CSF M/M3G/M6G ratio was
      1:47:5 (weight basis), 1:34:4 (molar basis) and the mean plasma ratio was
      M/M3G/M6G 1:150:23 (weight basis), 1:109:17 (molar basis). The mean M3G and M6G
      concentrations in CSF at steady state were 15-18% of those found in plasma. Pain
      relief, evaluated by a visual analogue scale (VAS), did not correlate with the
      CSF M3G concentrations or with the M3G/M ratio. Since CSF M6G concentrations were
      high, M6G could, however, contribute to pain relief. We conclude that after oral
      administration of slow-release morphine, there is a significant passage of the
      morphine glucuronide metabolites to the CSF and that the M3G and M6G metabolites
      in CSF are in the concentration range where they may have an influence on
      analgesia.

PMID- 8545140
TI  - Treatment of terminal cancer pain in France: a questionnaire study.
AB  - Compared with other European countries, French laws and restrictions concerning
      the use of opioids are of medium severity only. Still, together with Germany,
      Belgium and Spain, France belongs to the group of countries with a low national
      consumption of morphine, calculated by the International Narcotics Control Board
      of United Nations. In order to elucidate the current practice of French
      physicians treating cancer pain, a questionnaire study was carried out, using the
      nationwide register of general practitioners and specialists of a pharmaceutical
      company. The knowledge of the principles and methods of cancer pain treatment
      were evaluated with 9 open and 19 multiple-choice questions. The ability of the
      physicians to apply their knowledge in practice was evaluated by analyzing their
      suggested treatment of 3 illustrative case histories. The favourite drugs in
      treating cancer pain were strong opioid agonists, suggested by 25% of the general
      practitioners and 44% of the specialists for a typical cancer pain patient. The
      recommended daily doses of opioids were mostly far below the level generally
      accepted in palliative care. The drug of choice for metastatic bone pain was a
      combination of paracetamol and codeine, chosen by a third of the general
      practitioners. Consequently, only 10% and 21% of the treatment suggestions were
      regarded as adequate. Ninety-two percent of the physicians experienced
      difficulties in the treatment of cancer pain, inefficacy of treatment being the
      most important problem.

PMID- 8545141
TI  - Double-blind, placebo-controlled study of the application of capsaicin cream in
      chronic distal painful polyneuropathy.
AB  - We have completed a 12-week double-blind, placebo-controlled randomized study on
      the efficacy of the application of capsaicin (CAPS) cream (0.075%) in the
      treatment of chronic distal painful polyneuropathy. Forty patients were enrolled
      and 39 completed the study. The 2 limbs were randomly assigned to CAPS or placebo
      (PLAC). The cream was applied 4 times a day. The first tube contained the active
      PLAC, methyl nicotinate. In the final 4 weeks (single-blind wash-out phase), PLAC
      was administered bilaterally. Efficacy was evaluated using the following scales:
      (1) investigator global, (2) patient global, (3) visual analog (VAS) of pain
      severity, (4) VAS of pain relief, (5) activities of daily living, and (6)
      allodynia. Patients were examined at onset and at monthly intervals using a
      neurologic disability scale, nerve conduction studies, computer-assisted sensory
      examination for vibration and thermal cooling and warming, QSART (quantitative
      sudomotor axon reflex test) and quantitative flare response. There was no
      statistical evidence of efficacy of CAPS cream over PLAC for any of the pain
      indices. At early time points (1-4 weeks), there were a small number of indices
      that favored the PLAC. The percent of limbs that improved on the investigator's
      global scale were 51.3 vs. 53.8 at 4 weeks, 56.4 vs. 64.1 at 8 weeks and 59 vs.
      66.7 at 12 weeks for CAPS vs. PLAC; no statistically significant difference was
      found. All the safety indices showed no difference between sides. We interpret
      the early hyperalgesia on the CAPS side as being responsible for the better
      performance of PLAC at early time points. The large percentage of limbs that
      improved may be a pronounced PLAC response.

PMID- 8545142
TI  - Efficacy of controlled-release codeine in chronic non-malignant pain: a
      randomized, placebo-controlled clinical trial.
AB  - Treatment decisions for the use of opioid analgesics in chronic non-malignant
      pain are based primarily on survey data, as evidence from well-controlled
      clinical trials has been lacking. Forty-six patients with chronic non-malignant
      pain were enrolled in a randomized, double-blind, placebo-controlled evaluation
      of controlled-release (CR) codeine. Following a 3-7-day diary familiarization
      period, patients were randomly assigned to 7 days of treatment each with CR
      codeine q12h or placebo. The CR codeine dose was determined from the consumption
      of acetaminophen+codeine in the 7 days preceding the study. During both phases,
      breakthrough pain was treated with acetaminophen+codeine every 4 h as required.
      Pain intensity was assessed at 08:00 h and 20:00 h using a visual analogue scale
      (VAS) and a 5-point categorical scale, and rescue analgesic consumption was
      recorded at the time of use. Thirty patients (17 female, 13 male; mean age: 55.1
      +/- 13.4 years) completed the study and were treated with a mean daily CR codeine
      dose of 273 +/- 78 mg (range: 200-400 mg). CR codeine treatment resulted in
      significantly lower overall VAS pain intensity scores (35 +/- 18 vs. 49 +/- 16, P
      = 0.0001), categorical pain intensity scores (1.7 +/- 0.6 vs. 2.2 +/- 0.6, P =
      0.0001), and in pain scores by day of treatment and by time of day. Daily rescue
      analgesic consumption was significantly lower on CR codeine, relative to placebo
      treatment (3.6 +/- 3.5 vs. 6.1 +/- 3.2 tablets/day, P = 0.0001). There was also a
      significant reduction in the Pain Disability Index (PDI) on CR codeine, compared
      to placebo (25.0 +/- 7.7 vs. 35.1 +/- 8.2, P = 0.0001). Patients' and
      investigators' blinded treatment preference was significantly in favor of CR
      codeine, relative to placebo (73% vs. 10%, P = 0.0160 and 80% vs. 7%, P = 0.0014,
      respectively). The incidence of nausea was significantly higher on CR codeine
      than on placebo (32.6% vs. 11.9%, P = 0.013). Ninety-three percent of patients
      completing the study requested long-term, open-label treatment with CR codeine.
      Pain intensity scores at the completion of 19 weeks of long-term evaluation were
      comparable to those during the double-blind CR codeine treatment. We conclude
      that treatment with CR codeine results in reduced pain and pain-related
      disability in patients with chronic non-malignant pain.

PMID- 8545143
TI  - Chronic use of symptomatic headache medications.
AB  - Chronic use of symptomatic headache medication is believed to be a risk factor
      for drug-induced chronic headache. This study reports the frequency of chronic
      use of symptomatic headache medications implicated in drug-induced chronic
      headache among primary-care headache (PCH) patients and identifies predictors of
      chronic/frequent use. The design uses a 2-year cohort study of a sample of PCH
      patients in Group Health Cooperative of Puget Sound, a large health maintenance
      organization in Seattle, WA. Among 779 PCH patients (aged 18-74 years)
      interviewed at baseline, 662 (85%) completed both 1- and 2-year follow-up
      interviews. This study estimates the percent of PCH patients reporting: (1)
      frequent use of over-the-counter, non-steroidal anti-inflammatory, opioid,
      sedative-hypnotic, and ergot medications (defined as 14 or more days of use for
      each class in the prior month), (2) chronic/frequent use of these medications,
      defined as surpassing criteria for frequent use on at least 2 of the 3 study
      interviews, and (3) chronic/frequent polypharmacy, defined as chronic/frequent
      use of 2 or more classes of headache medication. Twenty-one percent of PCH
      patients were chronic/frequent users of symptomatic headache medications, while
      2.6% met study criteria for chronic/frequent polypharmacy. Chronic/frequent use
      of over-the-counter medications (15.9%) was twice as common as chronic/frequent
      use of prescription medications (7.7%). Headache days at baseline was the
      strongest predictor of chronic/frequent medication use. After controlling for
      baseline persistence and severity, older patients were more likely to be
      chronic/frequent users of headache medications. The age effect was explained by
      chronic/frequent use of over-the-counter medications.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8545144
TI  - Inflammatory models of cutaneous hyperalgesia are sensitive to effects of
      ibuprofen in man.
AB  - A new experimental procedure was developed to quantify the analgesic actions of
      non-steroidal anti-inflammatory drugs (NSAIDs) in healthy human subjects. In
      order to mimic the clinical situation, the drug was 'therapeutically'
      administered 1 day after induction of inflammation by freezing a small skin area.
      The procedure was easily tolerated and led to a marked hyperalgesia without
      ongoing pain which was tested using mechanical impact stimulation and magnitude
      estimation. For comparison, we used a previously established model of repeated
      noxious pinching of an interdigital skin web which induces a hyperalgesia to
      pressure (rated via visual analogue scale), and topical application of capsaicin
      which leads to quantifiable flare and allodynia responses. The effects of a
      cumulative drug regime of ibuprofen in 2 different doses (3 x 400 mg and 3 x 800
      mg at 2-h intervals) were tested versus placebo using a double-blind cross-over
      design with 24 volunteers of either gender. Ibuprofen caused a significant
      suppression of the hyperalgesia to repeated pinching and of the hyperalgesia to
      impact stimulation following freeze trauma. In contrast, there was no effect on
      the areas of flare and allodynia induced by capsaicin application and on the
      impact evoked sensations from untreated skin. The two dosages of ibuprofen,
      however, appeared to be equally effective in a way that suggests a plateauing of
      the antihyperalgesic effect. The two models in which hyperalgesia is affected by
      ibuprofen, i.e., repeated pinching and impact stimulation after freeze trauma,
      seem to provide comparable sensitivity. The freeze model may in the future have
      the advantage to allow for a better temporal resolution of the drug's action
      profile.

PMID- 8545145
TI  - Dorsal horn convergent neurones: negative feedback triggered by spatial summation
      of nociceptive afferents.
AB  - In order to investigate the effects of spatial summation on the spinal
      transmission of nociceptive information, we compared in intact and spinal
      anaesthetized rats, responses of lumbar convergent neurones elicited by noxious
      heat stimuli applied to areas of the body much greater in size than their
      individual excitatory receptive fields, located distally on the hindpaw. Twenty
      four neurones were recorded in each group of animals. For each neurone, 4
      successive immersions of increasing areas (1.9-18 cm2) of the ipsilateral hindpaw
      in a 48 degrees C water bath (15-sec duration) were performed with 10-min
      intervals in a randomized and balanced order. In intact animals, the responses of
      convergent neurones progressively decreased when the area of noxious thermal
      stimulation reached and then exceeded approximately twice the area of their
      individual excitatory receptive fields. This decrease was highly significant for
      18 cm2 which represents approximately 10-fold the mean of the receptive field
      areas. Such a phenomenon was not observed for neurones recorded in spinal animals
      although their excitatory receptive field areas were not significantly different.
      These results suggest that the activation of a large population of nociceptive
      afferents triggers supraspinally mediated negative feed-back loop modulating the
      responses of convergent neurones.

PMID- 8545146
TI  - Central sensitization as a result of surgical pain: investigation of the pre
      emptive value of pethidine for ovariohysterectomy in the rat.
AB  - The development of central hypersensitivity as a result of a routine surgical
      procedure, midline ovariohysterectomy, was investigated in rats using the paw
      pressure test (PPT) and tail-flick latency (TFL) tests of spinal reflex activity.
      In addition, the modulating effect of pre-emptive versus post-operative
      administration of pethidine (a short-acting pure mu-opioid agonist) on the
      development of central hypersensitivity was studied. Initial experiments
      indicated that pethidine (15 mg/kg, i.m.) gave sub-maximal increases in
      thresholds for 60 min, and also that the administration of an anaesthetic did not
      unduly prolong the action of pethidine. Subsequently, 24 female Wistar rats were
      allocated to 1 of 4 treatment protocols: (1) anaesthesia without analgesics; (2)
      anaesthesia and surgery (midline ovariohysterectomy) without analgesics; (3)
      anaesthesia and surgery with pre-operative administration of pethidine; (4)
      anaesthesia and surgery with post-operative administration of pethidine. Thirty
      five minutes after the end of anaesthesia thermal and mechanical nociceptive
      thresholds were measured at stepwise increasing intervals for 480 min. Changes
      were expressed as percentage changes from baseline (PPT) or deviation from
      expected values (TFL). Area under the threshold versus time response curves
      (AUCs) were also calculated for the following time sectors: 30-90, 90-150, 150
      270, 270-390 and 390-510 min post-anaesthetic. Results of the TFL testing did not
      indicate the development of any significant hyperalgesia in any groups, but the
      results of the PPT did. In the time sectors 150-270 and 270-390 min post
      anaesthetic, the AUCs in rats subjected to anaesthesia and surgery with either
      post-operative administration of pethidine or surgery with no analgesic drug
      administration, were significantly lower than the AUCs in rats given analgesics
      pre-operatively or those subjected to general anaesthesia alone (P < 0.01), Mann
      Whitney). In summary, it appears that pethidine, in this protocol, prevented the
      development of surgically induced hyperalgesia when it was given pre-emptively.

PMID- 8545147
TI  - Plasma atrial natriuretic factor levels, impaired myocardial contractility and
      pain intensity in uncomplicated acute myocardial infarction.
AB  - To investigate the relationship between plasma atrial natriuretic factor (ANF)
      levels, impaired myocardial contractility and pain intensity in acute myocardial
      infarction (AMI) we introduced a procedure estimating the pain component not
      influenced by the individual emotional reaction to stress, i.e., the original
      pain sensation. We deduced this pain component during AMI by correcting the
      personal report of AMI pain, quantified on a VAS, with the emotional reaction of
      each patient estimated by using a custom-built instrument which applies
      electrical stimuli of different intensities. Twenty-five patients with
      uncomplicated AMI were studied. According to plasma ANF levels and AMI pain
      values reported on the VAS, patients were categorized into 2 groups: pain and no
      pain. Plasma ANF levels were significantly lower in pain (35.9 +/- 2.5 pg/ml)
      than in no-pain patients (70.8 +/- 3.3 pg/ml), whereas the ejection fraction (EF)
      was significantly higher in pain (49.6 +/- 1.7%) than in no-pain patients (29.3
      +/- 1.9%). Within each group, a negative correlation was found between ANF and
      EF; the corresponding regression lines did not differ significantly in their
      slopes or intercepts, suggesting that AMI pain does not affect ANF release. The
      significant negative correlation between original pain sensation and EF found in
      pain patients indicates that this pain component may be useful to gauge the
      severity of impaired myocardial contractility during AMI. Moreover, the much
      higher plasma ANF levels observed in no-pain patients suggest that ANF may be
      involved in preventing AMI pain.

PMID- 8545148
TI  - Nerve growth factor induces mechanical allodynia associated with novel A fibre
      evoked spinal reflex activity and enhanced neurokinin-1 receptor activation in
      the rat.
AB  - A single dose of nerve growth factor (NGF, 1 microgram/g, i.p.) administered to
      rats aged between postnatal days (PND) 12 and 14 resulted in a behavioural
      hypersensitivity of the hindlimb flexion withdrawal reflex to mechanical stimuli
      which developed 2 h after NGF and remained significant for 24 h. Heat
      hyperalgesia occurred some 4 h following NGF injection and lasted for 24 h.
      Isolated spinal cords were prepared from animals treated with NGF and were
      maintained in vitro for physiological and pharmacological analysis of lumbar
      spinal reflex activity. Repetitive, low-frequency group I/II A beta-fibre
      stimulation evoked a novel wind-up response after NGF injection similar to that
      produced by C-fiber group III/IV stimulation in normal animals. The neurokinin-1
      (NK1) receptor antagonist RP67580 reduced the C fiber-evoked responses following
      NGF treatment but not in naive preparations. The novel A beta fiber-evoked wind
      up response was also reduced by RP67580. The NGF-induced changes in NK1 receptor
      responses occurred in the absence of any detectable changes in either spinal cord
      NK1 receptor dose-response relationships or NK1 receptor mRNA levels. These
      findings are likely to be related to the behavioural allodynia observed in the
      present study and to central excitability changes observed after chronic
      inflammation where NGF levels are increased.

PMID- 8545149
TI  - A cost-of-illness study of back pain in The Netherlands.
AB  - In this study we estimated the costs of back pain to society in The Netherlands
      in 1991 to be 1.7% of the GNP. The results also show that musculoskeletal
      diseases are the fifth most expensive disease category regarding hospital care,
      and the most expensive regarding work absenteeism and disablement. One-third of
      the hospital care costs and one-half of the costs of absenteeism and disablement
      due to musculoskeletal disease were due to back pain. The total direct medical
      costs of back pain were estimated at US$367.6 million. The total costs of
      hospital care due to back pain constituted the largest part of the direct medical
      costs and were estimated at US$200 million. The mean costs of hospital care for
      back pain per case were US$3856 for an inpatient and US$199 for an outpatient.
      The total indirect costs of back pain for the entire labour force in The
      Netherlands in 1991 were estimated at US$4.6 billion; US$3.1 billion was due to
      absenteeism and US$1.5 billion to disablement. The mean costs per case of
      absenteeism and disablement due to back pain were US$4622 and US$9493,
      respectively. The indirect costs constituted 93% of the total costs of back pain,
      the direct medical costs contributed only 7%. It is therefore concluded that back
      pain is not only a major medical problem but also a major economical problem.

PMID- 8545150
TI  - Is myofascial pain of the temporal muscles relieved by oral sumatriptan? A cross
      over pilot study.
AB  - There is evidence that serotonin may be implicated in the pathophysiology of
      myofascial pain (MFP). Because of this, we used oral sumatriptan (Imitrex,
      Glaxo), a peripherally acting agonist of 5-HT1D receptors, in a double-blind,
      randomized, placebo-controlled double crossover pilot study of 7 patients with
      episodic MFP of the temporalis muscles. The results showed that there was a
      significant reduction in pain intensity and increase in pain relief over time
      with both the active medication and the placebo, but no significant difference
      between treatments. All but 1 patient reported that they are not interested in
      retaking the same medication. These data suggest that oral sumatriptan may not be
      the drug of choice in the control of episodic MFP.

PMID- 8545151
TI  - Long-term epidural analgesia for pregnancy-induced intercostal neuralgia.
AB  - Intercostal neuralgia is one of many possible neurological disorders associated
      with pregnancy. A woman presented in the 34th week of her 4th pregnancy with
      progressing right-sided pain and hypoesthesia in the ribs, right upper quadrant
      of the abdomen, and mid-thoracic area of her back. With a clinical diagnosis of
      pregnancy-related intercostal neuralgia, we inserted an epidural catheter at T8
      for ambulatory pain management. A continuous infusion of bupivacaine was titrated
      by concentration and rate until adequate analgesia was obtained. The final
      effective dose consisted of 0.125% bupivacaine at 6 ml/h with a patient
      controlled bolus dose of 2 ml every 30 min as needed (4-6 boluses per 24-h
      period). This allowed the patient to continue to work full-time and perform daily
      activities with minimal discomfort. The epidural infusion was continued until the
      patient went into spontaneous labor 28 days after the initial clinical visit. A
      full-term infant was delivered without incident. No major complications occurred
      such as local anesthetic toxicity, hypotension, motor weakness, or infection.
      Minor complications included disconnection of the catheter cap and accidental
      dislodgment, which required placement of a second epidural catheter. For this
      patient, an appropriately placed chronic epidural catheter and a titrated
      continuous infusion of bupivacaine provided adequate and safe analgesia for
      pregnancy-associated intercostal neuralgia.

PMID- 8545152
TI  - Comments on Cheshire et al. (PAIN, 59 (1994) 65-69)

PMID- 8545153
TI  - Comments on Bendtsen et al. (PAIN, 59 (1994) 235-239)

PMID- 8545154
TI  - Pressure-sensitive devices.

PMID- 8545155
TI  - Comments on Jaffe and Rowe.

PMID- 8545156
TI  - Morphine's name.

PMID- 8545157
TI  - A pediatrician's view: anyone for a game of bridge?

PMID- 8545158
TI  - Where will you send your sick neonates?

PMID- 8545159
TI  - Regionalized care established by neonatal intensive care units.

PMID- 8545160
TI  - Thermoregulation.

PMID- 8545161
TI  - Controversies in neonatal resuscitation.

PMID- 8545162
TI  - Clinical rounds in the well-baby nursery: treating jaundiced newborns.
AB  - Ten pearls (and pitfalls) in the management of the jaundiced newborn: Remember to
      take a history. Ask about jaundice in previous siblings and check family
      ethnicity. Don't ignore jaundice in the first 24 hours--it is considered
      pathologic until proven otherwise. Some normal infants may appear jaundiced and
      have a bilirubin level of 5 mg/dL at 23 hours and 59 minutes. On the other hand,
      a bilirubin level of 5 mg/dL at 10 hours is almost certainly pathologic. Use your
      judgment. Don't treat 35 to 37 week gestation infants as if they were full-term
      infants. Although these babies are cared for in well-baby nurseries and are
      generally treated like full-term infants, they are not full term. They are not as
      vigorous and do not nurse as well as full-term infants. Infants at 37 weeks
      gestation are four times more likely to have a serum bilirubin level greater than
      13 mg/dL than those at 40 weeks gestation. Don't send 35-week gestation infants
      home before 48 hours. Document your assessment, particularly if the infant is
      being discharged early. Document the presence or absence of jaundice and its
      severity. A late rising bilirubin is typical of G6PD deficiency. Think about the
      ethnic background: G6PD deficiency is much more likely to occur in families from
      Greece, Turkey, Sardinia, and Nigeria, and particularly in Sephardic Jews from
      Iraq, Iran, Syria, and Kurdistan. Your practice may not contain many such
      families but remember in today's world of travel and intermarriage, etc, these
      genes are ubiquitous and the diagnosis of G6PD deficiency should always be
      considered in a newborn child with a significant elevation of bilirubin,
      particularly if it is a male and the rise in bilirubin is of late onset. Don't
      use homeopathic doses of phototherapy. As with any drug, phototherapy should be
      provided in a therapeutic dose (see above), but with the light sources commonly
      used, it is impossible to overdose the patient. Don't ignore a failure of
      response to phototherapy. If the bilirubin rises despite adequate phototherapy,
      there must be a reason. Consider the possibility of an unrecognized hemolytic
      process. Provide timely follow-up. Infants discharged (as most are) before 48
      hours should be seen by a health-care professional within 2 to 3 days of
      discharge. Don't ignore prolonged jaundice. About one in three normal breast-fed
      infants still will be clinically jaundiced when they are 2 weeks old (two thirds
      will be biochemically jaundiced). These infants all have indirect
      hyperbilirubinemia. Occasionally, however, an infant with prolonged jaundice has
      direct hyperbilirubinemia. In these infants, the diagnosis of biliary atresia or
      some other cause of cholestatic jaundice must be considered. If the infant is
      clinically jaundiced beyond age 2 weeks, you should: 1) check the newborn record
      to make sure that the metabolic screen for hypothyroidism is normal (congenital
      hypothyroidism is a cause of indirect hyperbilirubinemia), and 2) ask the mother
      about the color of the urine and stool. If the baby's stools are pale or the
      urine is dark yellow, you must get a direct bilirubin to rule out cholestasis. If
      there is direct hyperbilirubinemia, a urine dipstick will identify the presence
      of bile (bilirubin). If the color of the urine and stool are normal (by history),
      it is reasonable to follow the child for another week. However, any infant who is
      still jaundiced beyond age 3 weeks must have a measurement of direct bilirubin.
      Don't ignore severe jaundice. If the bilirubin is sufficiently elevated,
      kernicterus can occur in a healthy, breast-fed infant.

PMID- 8545163
TI  - Infant lung function and tidal breathing patterns.

PMID- 8545164
TI  - Relationship between an index of tidal flow and lower respiratory illness in the
      first year of life.
AB  - The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te)
      has been reported to be decreased in infants who later develop wheezing lower
      respiratory tract illness (LRI) in the first year of life. The relationship
      between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in
      whom the first measurement of pulmonary function (PFT) was made before the age of
      6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by
      standardized questionnaires at well-baby visits, through biweekly telephone calls
      to mothers, and review of all visits to physicians. Tme/Te was derived from 10
      tidal breathing loops during stable respiration. Partial expiratory flow-volume
      curves were obtained with the rapid compression technique, and passive
      respiratory mechanics were evaluated by the single breath occlusion technique.
      Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6
      months) to take into account the age-related decline in Tme/Te. Among 80 infants
      first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed
      a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the
      difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was
      observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females,
      decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and
      those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which
      included data for multiple measurements of Tme/Te over the first year of life and
      adjusted for age-at-test and maternal smoking during pregnancy also demonstrated
      a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P
      = 0.08). Level of Tme/Te was not consistently related to level of respiratory
      system resistance (RRS) or flow at functional residual capacity (VFRC). Level of
      VFRC has been shown previously to be related to the occurrence of LRI and in this
      study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only
      weakly associated with the development of LRI in the first year of life; (2) this
      ratio is a less precise and an epidemiologically less useful measure than is VFRC
      to investigate groups of infants with and without LRI and without clinically
      significant underlying lung disease.

PMID- 8545165
TI  - Measurement of lung volumes and pulmonary mechanics during weaning of newborn
      infants with intractable respiratory failure from extracorporeal membrane
      oxygenation.
AB  - Newborn infants with intractable respiratory failure who require extracorporeal
      membrane oxygenation (ECMO) experience diffuse pulmonary atelectasis shortly
      after initiation of ECMO. Atelectasis is likely due to the primary lung injury
      and the reduction of applied inspiratory ventilator pressure when the respirator
      settings are changed to the "rest settings." These pathophysiologic changes
      result in a decrease in lung compliance and lung volumes. We hypothesized that
      improving lung functions observed during ECMO and indicated by an increase in
      lung volumes will predict successful weaning from ECMO. Sixteen infants (mean +/-
      SEM: gestational age, 40.3 +/- 0.3 weeks; birth weight, 3.5 +/- 0.1 kg) with
      meconium aspiration syndrome (n = 13), sepsis (n = 2), and persistent pulmonary
      hypertension (n = 1) were studied. We measured passive respiratory system
      mechanics and lung volumes initially during full ECMO support (115 +/- 18 h on
      ECMO, Study I), and then within 24 h prior to weaning from ECMO (Study II).
      Respiratory system compliance (Crs), respiratory system resistance (Rrs),
      functional residual capacity (FRC), and tidal volume (VT) were measured. Prior to
      Study I lung volumes were too small to be detected. Crs increased between Study I
      and Study II (0.41 +/- 0.05 to 0.63 +/- 0.05 mL/cmH2O/kg, P < 0.05), and VT
      increased between Study I and Study II (5.6 +/- 0.6 to 10.4 +/- 0.8 mL/kg, P =
      0.0005). FRC increased from 3.6 +/- 1.0 to 7.9 +/- 0.9 mL/kg (P = 0.0001). There
      was no change in Rrs (88 +/- 8 to 89 +/- 6 cm H2O/L/s, P = 0.9). The combination
      of Crs > 0.5 mL/cmH2O/kg and FRC > 5 mL/kg was a better predictor (P = 0.0002) of
      readiness to wean from ECMO than either Crs (> 0.5 mL/cmH2O/kg, P = 0.057) or FRC
      (> 5 mL/kg, P = 0.007) alone. The combination of FRC and Crs had a sensitivity of
      73.3% and specificity of 100% for successful decannulation. We conclude that
      repeated measurements of FRC and Crs can assess lung recovery and may assist in
      establishing criteria for successful weaning from ECMO.

PMID- 8545166
TI  - Biochemical lung maturity, static respiratory compliance, and pulmonary gas
      transfer in intubated preterm infants with and without respiratory distress
      syndrome.
AB  - We investigated the relationship between tests of biochemical lung maturity
      [lecithin/sphingomyelin ratio (L/S ratio)], static compliance of the respiratory
      system (Crs), and estimates of pulmonary gas transfer [venous admixture and
      arterial/alveolar (a/A) ratio] in a group of intubated preterm infants with and
      without respiratory distress syndrome (RDS). Thirty infants were studied once (n
      = 26) or twice (n = 4). The L/S ratio was obtained by means of high-performance
      thin-layer chromatography and determination of the phosphorus content. Crs was
      obtained by the multiple occlusion technique. Transcutaneous blood gases and the
      percentage of oxygen in the inspired gas were recorded and estimates of pulmonary
      gas transfer were calculated using algorithms. L/S ratio and Crs correlated well
      (r = 0.73), indicating a higher compliance in biochemically more mature lungs.
      Both the a/A ratio and venous admixture correlated significantly with the L/S
      ratio and Crs (P < 0.001). Crs, L/S ratio, and a/A ratio decreased with
      increasing severity of radiological RDS, and the percentage venous admixture
      increased (P < 0.001). Sequential measurements in four infants during the acute
      phase and after RDS resolved indicated that clinical improvement coincided with
      improvements in biochemical lung maturity, Crs, and estimates of pulmonary gas
      transfer.

PMID- 8545167
TI  - Glutathione metabolism in newborns: evidence for glutathione deficiency in
      plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures.
AB  - Respiratory distress in premature newborns is associated with deficiency of
      surfactant in the bronchoalveolar lining fluid; this may be influenced by a local
      deficiency of antioxidants. Severe L-buthionine-S,R-sulfoximine-induced depletion
      of glutathione (GSH, a major antioxidant) in rodents is associated with lung type
      2 cell lamellar body damage and decreased concentrations in lung and
      bronchoalveolar lavage fluid (BALF) of phosphatidyl choline (a major component of
      surfactant). At birth, prematurely born newborns (30-34 weeks) had lower
      peripheral venous plasma GSH concentrations than term (> 36 weeks) babies; these
      levels decreased further with increasing prematurity (< 27 weeks, with
      respiratory distress). On day 2, the peripheral venous plasma GSH concentrations
      reached a nadir, and the lowest levels were found in the most premature newborns.
      Lymphocyte GSH concentrations were lowest on day 2 and day 7, and in prematures
      (< 27 weeks, with respiratory distress) remained below adult lymphocyte GSH
      levels for at least 4 weeks. At birth, prematures (< 27 weeks, with respiratory
      distress) had a central plasma arterio-venous (A-V) GSH gradient across the lung
      (an estimate of lung uptake of GSH) of 0.72 +/- 0.15 (mean +/- SD) mumol/L; on
      day 2, the A-V gradient did not change significantly (0.49 +/- 0.09 mumol/L). At
      birth, these prematures had markedly decreased BALF GSH concentrations (compared
      with adult levels), and they were not significantly changed during the first 4
      weeks of life. These results suggest that GSH deficiency is present in prematures
      and that it increases with the degree of prematurity. At birth, GSH deficiency
      will compromise the lungs' defense against oxidative stress injury. Oxidative
      stress is likely to increase if hyperoxic treatment is given for respiratory
      distress in these infants.

PMID- 8545168
TI  - Familial infantile apnea and immature beta oxidation.
AB  - Infants with inborn errors of fatty acid metabolism may present with apnea,
      periodic breathing, and sudden infant death syndrome (SIDS). Recognition of these
      disorders and initiation of appropriate therapy may prevent SIDS. Metabolic
      pathways develop during gestation and post-natally. We report three siblings with
      apnea and periodic breathing, as well as biochemical defects consistent with a
      non-specific abnormality of beta oxidation. One infant died a witnessed sudden
      infant death. The two survivors were treated with L-carnitine supplementation
      resulting in rapid resolution of both respiratory and metabolic abnormalities.
      Enzyme activity for short, medium, and long chain acyl coenzyme A dehydrogenases
      was normal in these two infants. Although a unique enzymatic deficiency was not
      identified, our experience with this family supports the need for routine
      biochemical evaluation of infants with "near miss" SIDS, also called acute life
      threatening events (ALTE), as well as those who have died of SIDS.

PMID- 8545169
TI  - Efficacy of surfactant therapy in infants managed with CPAP.
AB  - Surfactant rescue therapy can be utilized effectively early in the course of
      respiratory distress syndrome (RDS) in infants weighing > 1,000 g and treated
      exclusively with continuous positive airway pressure (CPAP) therapy. Thirteen
      infants (BW, 1,774 +/- 580 g; GA, 31 +/- 3 weeks) comprising the CPAP/SURFACTANT
      group were compared with 12 infants (BW, 1,753 +/- 556 g; GA, 31 +/- 2 weeks) who
      comprised the intermittent mandatory ventilation (IMV)/surfactant group, and with
      14 infants (BW, 1,776 +/- 332 g; GA, 32 +/- 2 weeks) treated with CPAP before
      surfactant was clinically available. A 5 mL/kg dose of Exosurf Neonatal
      (Burroughs-Wellcome) was administered to infants intratracheally when the FiO2
      requirement reached 0.40 to maintain the PO2 above 50 torr. Infants in the
      CPAP/surfactant group were intubated solely for surfactant administration and
      extubated within 18 +/- 6 min of treatment. The CPAP/surfactant group was treated
      at a mean age of 12.3 +/- 9.3 h, and the IMV/surfactant group at 10.2 +/- 9.8 h.
      Alveolar-arterial oxygen gradient (AaDO2), oxygenation index (OI), and mean
      airway pressure (MAP) were determined immediately before and after surfactant
      therapy, and at comparable times for the CPAP-only group. A significant
      difference was found in pre-treatment AaDO2, OI and MAP between the
      CPAP/surfactant group and IMV/surfactant group, but not between the
      CPAP/surfactant group and the CPAP-only group. Similarly, a significant
      difference in AaDO2, OI and MAP continued post-treatment was noted. However, a
      significant difference was also found at this time between the CPAP/surfactant
      group and the CPAP-only group. In addition, a significant difference was noted in
      AaDO2 and OI pre- and post-treatment within each surfactant-treated group.
      Furthermore, in the CPAP-only group AaDO2 and OI actually worsened (212 +/- 70
      vs. 239 +/- 68; 4.0 +/- 1 vs. 4.5 +/- 2, respectively). There was a significant
      reduction in the duration of oxygen therapy (3 +/- 2 vs. 5 +/- 2 vs. 4.5 +/- 2
      days, respectively) as well as in the total days of hospitalization (30 +/- 10
      vs. 42 +/- 15 vs. 43 +/- 12 days, respectively). We conclude that in this small
      group of infants surfactant administration was effective and safe. It appeared to
      improve the course of RDS and shorten the duration of oxygen exposure and days of
      hospitalization.

PMID- 8545170
TI  - Prolonged recovery from exercise-induced asthma with increasing age in childhood.
AB  - It has been suggested that children with asthma recover more quickly from
      exercise-induced bronchoconstriction than adults. On the basis of clinical
      observation we hypothesized that recovery rate from exercise-induced asthma (EIA)
      in childhood also decreases with age. In 14 children (aged 7-12 years) with a
      history of EIA, we measured spontaneous recovery from bronchoconstriction induced
      by two different stimuli: exercise and histamine. The children visited the
      laboratory three times. After a screening exercise test on the first visit,
      standardized bronchoprovocation tests with either exercise or histamine were
      performed on the following two visits in random order. The degree of
      bronchoconstriction induced by histamine was matched for that observed after
      exercise. During recovery, forced expiratory volume in 1 second (FEV1) was
      measured repeatedly up to 2 hours postchallenge. The recovery rate (% increase in
      FEV1/min) was calculated from the linear slope of the time-response curve.
      Differences in recovery rate between the two stimuli were analyzed by paired t
      test, and age-related differences were analyzed using multiple regression
      analysis. For the group as a whole, recovery rate was not different between the
      two stimuli (mean +/- SD: 1.22 +/- 0.91 for exercise, and 1.46 +/- 0.65, for
      histamine, P = 0.31). However, the recovery rate for exercise-induced
      bronchoconstriction decreased significantly with age (r = -0.74, P = 0.003), in
      contrast to the recovery rate for histamine (r = -0.15, P = 0.60). Consequently,
      in the oldest age group (11-12 years, n = 5) recovery rate from exercise
      challenge was significantly slower than in the younger age group (7-10 years, n =
      9), i.e., 0.54 +/- 0.17 and 1.60 +/- 0.93, respectively, P = 0.009, and slower
      than the recovery rate from histamine challenge: 0.54 +/- 0.17 and 1.33 +/- 0.54,
      respectively, P = 0.03. In the younger age group the recovery rates from exercise
      and histamine were not different (1.60 +/- 0.93 and 1.54 +/- 0.73, respectively,
      P = 0.83). We conclude that recovery from EIA in childhood decreases with
      increasing age. These data suggest that the mechanism of exercise-induced asthma
      in childhood changes with age. This might be due to changes in mediator
      production or response to mediator release.

PMID- 8545171
TI  - Time trends in acute childhood asthma in Basque Country, Spain.
AB  - To investigate recent changes in the epidemiology of acute asthma in children in
      a hospital setting, data from the Basque region of Bizkaia, Spain were reviewed
      for the period between 1987 and 1992. Over this period there was a 18% drop in
      hospital emergency visits for asthma in children aged 2-14 years from
      1,697/100,000 to 1,382/100,000. It was associated with a decline in the number of
      annual episodes per patient and in the number of patients needing further
      hospital treatment for the same episode. Paradoxically, hospital admission rates
      rose by 35.9% from 298/100,000 to 405/100,000. A trend toward decreasing length
      of hospital stay, a fall in the number of intensive care unit admissions, and an
      absence of in-hospital deaths were observed. Comparing data from September 1987
      with those of September 1992, a trend has been noticed toward greater intensity
      of emergency room treatment with increases in the number of doses of nebulized
      beta 2-agonists administered and in courses of oral prednisolone given. In
      September 1992 more patients were on maintenance "anti-inflammatory" inhaled
      therapy than in 1987.

PMID- 8545172
TI  - Cross-sectional study of bone density in asthmatic children.
AB  - The emphasis in treatment of asthma in children has shifted from bronchodilators
      to inhaled anti-inflammatory medications, including inhaled corticosteroids
      (ICS). Children with chronic asthma and moderate to severe symptoms have been
      targeted as particularly deserving of maintenance therapy with ICS. We have
      previously reported a cross-sectional study of bone density in children treated
      with ICS. There was no significant difference between the total bone density of
      asthmatic patients and controls. We sought to extend the information available on
      bone density in asthmatic children by evaluating 15 asthmatic subjects taking
      daily ICS (beclomethasone dipropionate) and comparing them with age- and sex
      matched controls. We compared total and regional bone density, bone age, and
      calcium intakes in these subjects. Asthmatic subjects were on ICS for 4-60
      months, with doses ranging from 200 to 450 micrograms/day. There was no
      significant difference between asthmatics and matched controls for height,
      weight, % RDA Ca2+, or bone age. The asthmatic subjects had bone density (total
      and regional measurements) equivalent to their controls. These results provide
      additional support for the safety of low-dose ICS on bone density in asthmatic
      children.

PMID- 8545173
TI  - Gastroesophageal reflux is chronologically correlated with coughing but not with
      wheezing in children with bronchial asthma and gastroesophageal reflux symptoms.

PMID- 8545174
TI  - On round pneumonia in children.

PMID- 8545175
TI  - Pediatric pulmonology: quo vadis?

PMID- 8545176
TI  - Pictorial essay: imaging of liver tumors in the infant and child.

PMID- 8545177
TI  - Unusual US and CT findings in hepatoblastoma: a case report.
AB  - Hepatoblastoma is the most common primary hepatic tumor in young children and its
      radiological findings have been well described. We report ultrasound and computer
      tomography findings in a case of hepatoblastoma diffusely involving the entire
      liver and presenting as inhomogeneity and numerous cystic lesions in the hepatic
      parenchyma.

PMID- 8545178
TI  - Papillary-cystic neoplasm of the pancreas.
AB  - Papillary-cystic neoplasm of the pancreas is a rare, nonfunctioning low-grade
      malignant tumor seen in young patients, most often female. Ultrasound and CT show
      a circumscribed, solid nonhomogeneous mass with cystic areas, with peripheral but
      not central enhancement and occasional calcification. Prognosis after excision is
      usually excellent. We describe a case of the papillary-cystic neoplasm of the
      pancreas in a 13-year-old girl to illustrate the radiological findings.

PMID- 8545179
TI  - Hyperinsulinism in children: diagnostic value of pancreatic venous sampling
      correlated with clinical, pathological and surgical outcome in 25 cases.
AB  - Neonatal hypoglycemia represents an emergency of heterogeneous etiology. The
      occurrence of persistent hypoglycemia caused by hyperinsulinism has not been well
      established. Some authors claim that it may be more common than previously
      suggested. The diagnostic goal is to distinguish hyperinsulinemia from other
      causes of hypoglycemia because management strategies differ. The diagnosis of
      persistent hypoglycemia attributable to hyperinsulinism is made when insulin
      secretion is excessive or inappropriate (> 10 microIU/ml). Medical management
      includes frequent feeding, high hydrocarbon intake, glucagon, diazoxide,
      somatostatin or steroid treatment. In case of resistance to medical intervention,
      surgery consisting of subtotal pancreatectomy is performed to avoid neurological
      sequelae. However, pediatric organic hypoglycemia secondary to hyperinsulinism
      can be caused by either diffuse or focal pancreatic lesions. Differentiation
      between these two types of lesion is necessary since partial pancreatectomy can
      prevent diabetes. In this prospective study, pancreatic venous sampling (PVS) was
      evaluated for the preoperative localization of lesions in 25 children with
      hyperinsulinism and correlated with surgical, pathological and clinical outcome.
      PVS is the most accurate preoperative technique for localizing focal lesions in
      children. Besides being safe and effective, it has the great advantage of
      detecting focal secretion, thus reducing the need for extensive surgery.

PMID- 8545181
TI  - Mesenteric cystic lymphangioma with myxoid degeneration: unusual CT and MR
      manifestations.
AB  - We report an unusual case of mesenteric cystic lymphangioma presenting as a large
      multilocular mass with a well-enhanced solid component and a central cleft, which
      were were pathologically correlated to the prominent stromal myxoid degeneration
      interspersed with abundant capillaries and the central fibrosis, respectively.
      The findings of computed tomography and magnetic resonance imaging are
      illustrated. Recognition of the multilocular configuration of the enhanced stroma
      may help to make the correct preoperative diagnosis.

PMID- 8545180
TI  - Doppler ultrasound and angiography of the vasculature of the liver in children
      after orthotopic liver transplantation: a prospective study.
AB  - Despite the availability of Doppler ultrasound, angiography still forms part of
      the protocol for evaluating children after orthotopic liver transplantation (OLT)
      at our department. To investigate whether Doppler ultrasound is a reliable method
      for evaluating the patency of the hepatic artery, portal vein, inferior vena
      cava, and the anastomotic site of the portal vein in children after OLT, we
      performed a prospective study in which Doppler ultrasound was compared with
      angiography in 38 children with 40 transplants (ten examinations on clinical
      demand and 49 examinations according to protocol). Good correlation was found in
      relation to demonstrating a patent hepatic artery (sensitivity 96% and
      specificity 100%). Two false-negative Doppler ultrasound results were
      attributable to technical difficulties and rejection. For evaluating the patency
      of the portal vein, Doppler ultrasound agreed with angiography in 58 of the 59
      examinations (98%). The one and only false-positive angiography result was
      explained by inadequate opacification. Doppler ultrasound visualized stenosis of
      the portal vein three times more often than angiography. In seven children,
      Doppler ultrasound findings suspicious of pathology of the inferior vena cava
      were confirmed using cavography or surgery. Doppler ultrasound proved to be a
      reliable technique for evaluating the patency of the hepatic artery, inferior
      vena cava, and portal vein and the anastomotic site of the portal vein.

PMID- 8545182
TI  - Retained foreign body: associations with elevated lead levels, pica, and duodenal
      anomaly.
AB  - A 14-month-old girl presented with elevated lead levels and a metallic foreign
      body was detected on abdominal radiograph. Subsequent evaluation, performed after
      the child failed to pass the foreign body with cathartics, revealed a bezoar
      proximal to a partial duodenal obstruction. The metallic foreign body was later
      removed and found to contain lead, however, the patient has subsequently had
      recurrent elevations of lead levels with episodes of pica. This case reiterates
      the need to evaluate children with retained foreign bodies for lead poisoning due
      to associated pica. In addition, retained foreign bodies should point to possible
      congenital anomaly of the duodenum causing partial obstruction.

PMID- 8545183
TI  - Hydrostatic reduction of intussusception under US guidance.
AB  - The current nonoperative management of ileocolic intussusception includes
      hydrostatic and pneumatic reduction, both performed under fluoroscopic
      monitoring. Recently, a new technique--ultrasound-guided reduction--replaced the
      conventional approach in our institution. Over a 20-month period, 46
      intussusceptions were diagnosed sonographically in 40 patients. In all cases,
      reduction was attempted under ultrasound guidance by means of a normal saline
      enema. In 42 cases (91%) reduction was successful and only four patients had to
      be operated (two resections, two manual reductions). Complications did not occur.
      This technique permits distinct visualization of the entire process, providing a
      clear and detailed echogram of the fluid-filled large and small intestine. We
      established the following definite criteria of reduction: disappearance of the
      target, demonstration of the ileocecal valve, visualization of the fluid reflux,
      and fluid filling of small bowel loops. The presented technique for the reduction
      of intussusception without radiation exposure is reliable and safe, and appears
      to be one of the most promising methods for the nonoperative treatment of
      ileocolic intussusception.

PMID- 8545184
TI  - Unrecognized retention of intraorbital graphite pencil fragments: the role of
      computerized tomography.
AB  - Children with unrecognized intraorbital pencil fragments may come to attention
      because of surrounding abscess and granuloma formation, after a long delay, and
      may be suspected to have an intraorbital neoplasm. Two such patients are
      reported, with emphasis on CT findings. Recognition of the CT manifestations of
      intraorbital pencil fragments may allow a more conservative surgical intervention
      than that for presumed intraorbital neoplasm.

PMID- 8545185
TI  - Intraspinal dislocation of the rib in neurofibromatosis: a case report.

PMID- 8545186
TI  - Desmoplastic infantile ganglioglioma: CT and MRI features.
AB  - We present three cases of desmoplastic infantile ganglioglioma in patients
      admitted to our institution in the past 8 years. CT and MR findings are
      discussed. Typically, these lesions are located in the frontal and parietal
      lobes, appearing as cystic tumors with a solid cortical component within the
      cerebrum, which enhances intensely, and moderate surrounding edema.

PMID- 8545187
TI  - Spontaneous regression of exostoses: two case reports.
AB  - Exostoses are a common skeletal disorder. Despite their incidence, little is yet
      known about their origin and biological behaviour. In particular, spontaneous
      regression of exostoses--an extremely rare event--is still a subject for debate.
      In this study, we describe two additional cases of spontaneous regression of
      exostosis; one was a solitary lesion while the other occurred in a patient with
      multiple heritable exostoses. Radiographic findings are presented along with some
      of the theories which aim at explaining this phenomenon.

PMID- 8545188
TI  - Clavicular horn: another bony projection in nail-patella syndrome.
AB  - Nail-patella syndrome is an uncommon inherited disorder characterized by nail
      dysplasia, iliac horns, and knee and elbow abnormalities. We report a patient
      with nail-patella syndrome in whom calvicular horn, shoulder girdle dysplasias,
      and pelvic abnormalities were demonstrated, along with the classical tetrad.

PMID- 8545189
TI  - Fetal bone age revisited: proposal of a new radiographic score.
AB  - In order to establish a fetal bone age score, the post-mortem skeletal
      radiographs of 85 selected normal fetuses aged from 15 to 41 weeks of gestation
      (WG) were analysed. Twenty-eight skeletal areas were selected for which
      quantitative and/or qualitative criteria were defined. Each new aspect was graded
      and statistically tested by the stepwise linear regression method. Two modalities
      of scores and decreasing complexity were then designed. The use of these two
      scores permitted the assessment of the fetal age with r2 values of 0.97 and 0.96
      (standard error of estimation of 1.19 and 1.36 WG). Applied to 15 intrauterine
      growth retardation (IUGR) fetuses, the age estimated by these scores was well
      correlated with the age obtained by extraosseous criteria of maturation. This
      method is proposed as a tool for determining, the fetal age during necropsy and
      could also be useful in US prenatal evaluation.

PMID- 8545190
TI  - Septic arthritis of the elbow in children: the role of sonography.
AB  - Twelve children with suspected septic arthritis of the elbow were prospectively
      studied with plain-film radiography and ultrasound. Imaging data were correlated
      with clinical history and final diagnosis. Joint effusion was seen by sonography
      in six patients, four of whom underwent ultrasound-guided joint aspiration,
      confirming the diagnosis of septic arthritis in two patients and excluding it in
      two. Of nine patients whose plain films showed only soft tissue swelling, seven
      had one or more significant findings with sonography: joint effusion (without fat
      pad elevation on lateral plain films) in three patients, periosteal reaction in
      two, and epitrochlear mass in three. Sonography confirmed soft tissue swelling
      alone in two patients, thus excluding the diagnosis of septic arthritis and
      obviating unnecessary attempts at joint aspiration. Sonography of the elbow is an
      informative, easily performed examination, which is capable of showing both intra
      and extra-articular abnormalities not apparent by plain radiography. Both the
      demonstration of pathologic changes and the failure to show joint fluid may
      affect clinical management.

PMID- 8545191
TI  - Congenital syphilis mimicking child abuse.
AB  - It has been reported that fractures complicating congenital syphilis can mimic
      child abuse. We present such a finding in an 8-week-old infant who presented with
      paralysis of the left arm.

PMID- 8545192
TI  - Distal humeral physeal injuries in child abuse: MR imaging and ultrasonography
      findings.
AB  - Distal humeral physeal injuries, in particular, fracture-separation of the distal
      humeral epiphysis, can be seen in abused infants. Detection of physeal injury in
      an infant or toddler may indicate the possibility of unsuspected abuse,
      particularly when an appropriate history explaining the circumstance of the
      fracture is lacking. In addition, the extent of injury can be difficult to
      characterize on plain radiographs. Ultrasonography (US) and MR imaging (MRI) may
      be of value in diagnosis and may obviate the need for intraoperative
      arthrography. We present MRI findings in three abused children with distal
      humeral physeal injuries. Sonographic correlation is also presented in one case.

PMID- 8545193
TI  - Child abuse fracture through physiologic periosteal reaction.
AB  - Because infants from 1 to 6 months of age often normally show symmetric
      diaphyseal periosteal reaction, careful analysis of the reaction at a midshaft
      fracture site is needed to date the fracture, especially in a child-abuse
      evaluation. We present a case of an acute fracture through such physiologic
      reaction.

PMID- 8545194
TI  - Hurthle cell carcinoma in an autonomous thyroid nodule in an adolescent.
AB  - A 16-year-old girl presented with a palpable thyroid nodule which was found to be
      functioning autonomously by radioiodine (123I) scintigraphy. After needle biopsy
      proved non-diagnostic, surgical excision showed the nodule to be Hurthle cell
      carcinoma. Functional thyroid nodules are rarely malignant, thyroid carcinoma is
      rare in childhood, and Hurthle cell carcinoma is a rare thyroid neoplasm, so the
      presence of these three rare conditions in one patient makes it a very unusual
      case.

PMID- 8545195
TI  - A dumbbell spinal lipoma presenting as a neck mass: CT and MR demonstration.
AB  - A case of histologically confirmed spinal lipoma without associated spinal
      dysraphism is presented. This tumor appeared lobulated, extending through an
      enlarged neuroforamen to form a so-called dumbbell tumor. In a review of the
      literature, there were found to be only four case reports of a dumbbell spinal
      lipoma. Our case was unique in that it manifested as a neck mass without
      neurological deficits. The fatty nature of the tumor allowed easy detection by
      computed tomography (CT), as well as by magnetic resonance (MR) imaging. MR is
      judged to be superior to CT for preoperative planning by virtue of its superb
      intraspinal resolution and multiplanar capability, and should be the procedure of
      choice for evaluating spinal lipomas.

PMID- 8545196
TI  - Acute presentation of cystic adenomatoid malformation of the lung in a 9-year-old
      child.
AB  - Congenital cystic adenomatoid malformation of the lung (CCAM) is an uncommon
      developmental abnormality presenting most often in the neonatal period. We report
      the clinical, radiological and pathological findings in a 9-year-old boy who
      presented with acute chest pain.

PMID- 8545197
TI  - MRI demonstration of ureteral jet effect in a patient with a spinal
      ganglioneuroma.

PMID- 8545198
TI  - Diagnosis of Cushing's disease in children: the role of inferior petrosal sinus
      sampling.

PMID- 8545199
TI  - A multicenter, randomized trial comparing synthetic surfactant with modified
      bovine surfactant extract in the treatment of neonatal respiratory distress
      syndrome. Vermont-Oxford Neonatal Network.
AB  - OBJECTIVE: To compare the efficacy of a synthetic surfactant (Exosurf Neonatal,
      Burroughs-Wellcome Co) and a modified bovine surfactant extract (Survanta, Ross
      Laboratories) in the treatment of neonatal respiratory distress syndrome (RDS).
      DESIGN: Multicenter, randomized trial. SETTING: Thirty-eight neonatal intensive
      care units participating in the Vermont-Oxford Neonatal Network. PATIENTS:
      Premature infants (n = 1296) weighing 501 to 1500 g with RDS requiring assisted
      ventilation with 30% oxygen or more were enrolled within 6 hours of birth.
      INTERVENTIONS: Infants were randomly assigned to receive up to four intratracheal
      doses of the synthetic surfactant (Exosurf Neonatal, n = 644) or the modified
      bovine surfactant extract (Survanta, n = 652). MAIN OUTCOME MEASURE: The primary
      outcome measure was the occurrence of death or chronic lung disease 28 days after
      birth. RESULTS: Death or chronic lung disease occurred in 57% of the infants
      treated with Exosurf Neonatal and in 54% of those infants treated with Survanta
      (relative risk [RR], 0.95; 95% confidence interval [CI], 0.86 to 1.04). Infants
      with birth weights of 1001 to 1500 g who received Survanta had a significantly
      lower risk of chronic lung disease or death at 28 days (Survanta, 27% vs Exosurf,
      34%; RR, 0.78; 95% CI, 0.60 to 0.99). Treatment with Survanta led to significant
      improvement in several secondary outcome measures. Survanta-treated infants
      received less supplemental oxygen and had lower mean airway pressure 6 and 72
      hours after treatment. Survanta-treated infants had significantly fewer
      pneumothoraces (Survanta, 9% vs Exosurf, 15%; RR, 0.60; 95% CI, 0.44 to 0.81).
      There were no differences between the groups in the incidence of other neonatal
      complications. CONCLUSION: Although no differences were noted between Survanta-
      and Exosurf-treated infants regarding the primary outcome of death or chronic
      lung disease at 28 days of age, the significant improvement in secondary clinical
      outcomes suggests that Survanta is more effective than Exosurf Neonatal in the
      treatment of established RDS.

PMID- 8545200
TI  - Screening for congenital adrenal hyperplasia: the Delfia Screening Test
      overestimates serum 17-hydroxyprogesterone in preterm infants.
AB  - OBJECTIVE: To compare 17-hydroxyprogesterone (17-OHP) levels measured by
      quantitative serum radioimmunoassay (RIA), including an extraction step, and by
      screening fluoroimmunoassay (FIA) on blood spots in preterm infants. METHODS:
      Subjects were 39 healthy infants born at less than 31 weeks' gestational age.
      Each infant had weekly blood sampling, and RIA and FIA were performed on each
      sample. RESULTS: Two hundred twenty-seven samples were taken at 28 to 41 weeks'
      postconceptional age. Mean +/- SD 17-OHP measured by RIA was 11.4 +/- 11.1 nmol/L
      (0.4 +/- 0.4 micrograms/dL), and decreased over time. Mean +/- SD 17-OHP measured
      by FIA was 38.96 +/- 37.3 nmol/L, greater than 17-OHP (RIA). Log(delta FIA-RIA)
      was inversely related to postconceptional age (R2 = .39). CONCLUSION: Screening
      FIA of blood spots overestimates levels of 17-OHP in preterm infants and should
      not be used to determine the likelihood of congenital adrenal hyperplasia in this
      population. We have abandoned FIA screening for congenital adrenal hyperplasia in
      infants weighing less than 1500 g.

PMID- 8545201
TI  - Correlates of osteopenia in patients with cystic fibrosis.
AB  - OBJECTIVE: As the expected survival improves for individuals with cystic
      fibrosis, these individuals face myriad medical complications. The goals of this
      study were to examine the prevalence of osteopenia in children and adults with
      cystic fibrosis and to elucidate the risk factors associated with deficits in
      bone mineral. METHODOLOGY: We compared bone mineral levels in 49 patients (30
      female and 19 male) ages 8 through 48 years with those of age- and sex-matched
      control subjects. Lumbar spine, femoral neck, and whole-body bone mineral were
      measured by dual-energy radiographic absorptiometry and expressed in terms of
      bone mineral content, areal bone density (BMD), and bone mineral apparent density
      (BMAD), which corrects for differences in bone size. Clinical variables were
      evaluated as potential correlates of bone mineral. RESULTS: Patients with cystic
      fibrosis had significantly less bone mineral than did control subjects at all
      sites using all expressions of bone mass. Mean BMD z scores were -1.7 (lumbar
      spine), -1.9 (femoral neck), and -1.2 (whole body). BMAD z scores also were
      significantly low for age and gender. Twenty-six of the 49 patients (8
      adolescents) had significant osteopenia according to their BMD z scores; 14 of
      the 45 patients (5 adolescents) with available BMAD z scores had significantly
      low values at one or more sites. Age, pubertal stage, body mass, caloric
      expenditure, illness severity, glucocorticoid therapy, and gonadal function
      predicted bone mineral status. Serum parathyroid hormone and calcium,
      carbohydrate intake, and weight-bearing activity had limited predictive value.
      Daily calcium intake and cystic fibrosis transmembrane regulator genotype did not
      predict bone mineral status. CONCLUSIONS: Osteopenia is common at all ages in
      cystic fibrosis, suggesting that inadequate bone mineral accretion as well as
      increased bone loss contribute to the deficits in bone mineral observed. Several
      clinical factors seem to contribute to these deficits.

PMID- 8545202
TI  - Subplate neurons--missing link in brain injury of the premature infant?

PMID- 8545203
TI  - Practice-based outcomes research: crucial, feasible, and neglected.

PMID- 8545204
TI  - Extralobar pulmonary sequestration masquerading as a congenital pleural effusion.

PMID- 8545205
TI  - Pulmonary alveolar proteinosis: experience with eight pediatric cases and a
      review.
AB  - We report eight pediatric cases of pulmonary alveolar proteinosis (PAP) that
      illustrate the polymorphic nature of this disease: two cases with severe neonatal
      onset, three cases with progressive respiratory distress in patients under 1 year
      old, and three cases in older children with mild symptoms. Consanguineous parents
      or affected siblings were identified or suspected in four families. Three
      patients suffered from associated immune or blood disorders (severe combined
      immune deficiency, myelodysplasia). The respective roles of a macrophagic
      dysfunction and of an anomaly of the surfactant are discussed according to the
      various clinical presentations of pediatric PAP. We performed eight unilateral
      pulmonary lavages under endoscopy and selective ventilation for two patients
      under 7 kg in weight. These interventions led to progressive discontinuation of
      oxygen therapy in one case, and temporarily stabilized the disease for the
      second. Subsequent recurrence in this second patient was treated by massive
      lavage under extracorporeal oxygenation. A third infant was successfully
      transplanted with no recurrence within 3 years. Ambroxol was administered in one
      case. The three oldest children of our series remained asymptomatic, whereas
      three of the younger patients died. In the light of this experience, we propose
      that the treatment administered should be determined according to the age of the
      patient, the degree of respiratory deficiency, and the nature of any associated
      pathology.

PMID- 8545207
TI  - Esotropia in a child treated with a scopolamine patch for drooling.

PMID- 8545206
TI  - Learning-disabled males with a fragile X CGG expansion in the upper premutation
      size range.

PMID- 8545208
TI  - Vocal cord paralysis as a presentation of intrauterine infection with varicella
      zoster virus.

PMID- 8545209
TI  - The Society for Pediatric Research: from infancy to adulthood in sixty-five
      years.

PMID- 8545210
TI  - Reassessment of the indications for ribavirin therapy in respiratory syncytial
      virus infections. American Academy of Pediatrics Committee on Infectious
      Diseases.
AB  - The purpose of this statement is to inform practitioners about new information
      concerning lack of demonstrated clinical effectiveness of ribavirin in the
      treatment of infants with respiratory syncytial virus (RSV) disease. The intent
      of the new recommendation is to allow practitioners to decide whether ribavirin
      therapy is appropriate or not by taking into account the particular clinical
      situation and their own preferences. More definitive answers to the questions of
      ribavirin efficacy and effectiveness will require multi-institutional,
      prospective, randomized clinical trials. Recommendations may be modified as new
      information becomes available.

PMID- 8545211
TI  - Does surgical subspecialization in pediatrics provide high-quality, cost
      effective patient care?
AB  - OBJECTIVE: To determine if pediatric surgical subspecialization provides cost
      effective, high-quality pediatric patient care. METHODS: Ureteroneocystostomy
      inpatients over 4 years were studied. Hospital charges and complications were
      compared between general urologists and fellowship-trained pediatric urologists.
      RESULTS: Hospital charges were significantly less ($1095) for patients under the
      care of a pediatric urologist. Complication rates were also lower. CONCLUSIONS:
      Pediatric urology subspecialization offers high-quality, cost-effective pediatric
      patient care.

PMID- 8545212
TI  - The prenatal visit. American Academy of Pediatrics Committee on Psychosocial
      Aspects of Child and Family Health.

PMID- 8545213
TI  - Recommended childhood immunization schedule. American Academy of Pediatrics
      Committee on Infectious Diseases.

PMID- 8545214
TI  - Dexamethasone for bacterial meningitis.

PMID- 8545215
TI  - Examination findings in legally confirmed child sexual abuse: it's normal to be
      normal.

PMID- 8545216
TI  - Postexposure prophylaxis of varicella in children with leukemia by oral
      acyclovir.

PMID- 8545217
TI  - Early prediction of the development of microcephaly after hypoxic-ischemic
      encephalopathy in the full-term newborn.

PMID- 8545218
TI  - An every other year cyclic epidemic of infants hospitalized with respiratory
      syncytial virus.

PMID- 8545219
TI  - The behavioral and emotional well-being of school-age children with different
      birth weights.
AB  - OBJECTIVE: To describe the mental and emotional well-being of children born at
      different birth weights assessed at school age and to identify neonatal,
      intervening health, and sociodemographic and environmental factors associated
      with mental and emotional well-being. METHODS: To address this issue, we used a
      prospective cohort study involving two previously studied cohorts, which were
      recontacted at 8 to 10 years of age to provide a multisite sample of 247 children
      weighing 1000 g or less at birth, 364 weighing 1001 to 1500 g, 724 weighing 1501
      to 2500 g, and 533 weighing more than 2500 g. Maternal reports were obtained on
      three standardized measures of mental and emotional well-being (the Rand General
      Well-being Scale, the Behavior Problem Index, and the Harter Scale of Child
      Competence) and on intervening health, sociodemographic, and environmental
      variables. Neonatal variables were derived from records at birth. Statistical
      techniques included analysis of variance and ordinary least squares multiple
      regression. RESULTS: Lower birth weight children did not differ on the General
      Well-being Scale but were more likely to have behavior problems and to be
      considered less competent. Other important correlates of mental and emotional
      well-being included childhood illness, maternal mental health, home environment
      score, and exposure to household cigarette smoking. CONCLUSION: Although lower
      birth weight children have poorer mental and emotional well-being, a substantial
      portion of this adverse outcome reflects modifiable environmental factors.

PMID- 8545220
TI  - Children's access to primary care: differences by race, income, and insurance
      status.
AB  - OBJECTIVE: Congressional initiatives to reduce spending under major public
      programs designed to improve access to health care have brought renewed attention
      to the health care needs of traditionally disadvantaged populations. The
      objective of this study was to assess access to and use of primary care services
      for poor, minority, and uninsured children in the United States. DESIGN AND
      SETTING: We analyzed data on 7578 1- to 17-year-old children of families
      responding to the 1987 National Medical Expenditure Survey, a nationally
      representative sample of families and children. OUTCOME MEASURES: Adult
      respondents were asked to report on several measures of access and use of care
      for children in the household. These included the presence of a usual source of
      care and its characteristics (type of site, travel time, waiting time, after
      hours care, and availability of a regular physician). We also examined the volume
      of physician contacts relative to the sample child's health status, the receipt
      of measles vaccinations, and whether children received care in response to
      selected symptoms of ill health. Results are presented for children generally and
      for four subgroups: poor children; minority children; uninsured children; and
      white, non-poor, insured children (the reference group). RESULTS: Poor, minority,
      and uninsured children fared consistently worse than the children in the
      reference group on all indicators studied. For example, children in each of the
      three at-risk groups were twice as likely as the children in the reference group
      to lack usual sources of care, nearly twice as likely to wait 60 minutes or more
      at their sites of care, and used only about half as many physician services after
      adjusting for health status. Multivariate analyses revealed that poverty,
      minority status, and absence of insurance exert independent effects on access to
      and use of primary care. CONCLUSIONS: The existence of substantial barriers to
      the access to and use of primary care for low-income, minority, and uninsured
      children is cause for significant concern, especially in an era of program
      cutbacks. New initiatives are needed to address both financial and non-financial
      barriers to the receipt of primary care for disenfranchised children.

PMID- 8545221
TI  - Psychosocial factors in childhood pedestrian injury: a matched case-control
      study. Kid's'n'Cars Team.
AB  - HYPOTHESIS: Psychosocial factors--such as hyperactivity and low family cohesion-
      contribute to the risk for child pedestrian injury (PI), even after controlling
      for known demographic risk factors. PARTICIPANTS: Urban PI victims aged 5 to 12
      years were recruited from one large, urban pediatric trauma center in a large
      city. One hundred twenty-eight cases were matched to uninjured children on age,
      sex, race, location of residence, and parental education. Among matched cases:
      70% were male, 41% were black, 33% were Hispanic, and 66% of the mothers had a
      high school education or less. RESEARCH DESIGN AND MEASUREMENTS: Case-control
      comparisons on 19 psychosocial variables drawn from interviews and standardized
      tests, using one-tailed matched-pairs t tests and conditional logistic regression
      analyses. RESULTS: Cases had higher reported physical quotient [PQ] (P = .01),
      self-help quotient (P = .04), and family stress (P = .02), and lower family
      supportiveness (P = .03). Multivariate analyses confirmed that PQ was higher in
      cases (10-point increase: odds ratio (OR) = 1.32 [90% confidence interval (CI)
      1.01-1.76], that stress was higher in cases (1 log increase: OR 2.13, [1.26
      3.61]), and that cases had lower family supportiveness (25-point decrease: OR
      1.43 [1.25-1.63]). It also identified household crowding as a factor for non
      black cases (OR for increase of 0.25 people per room: 2.18, [1.31-3.62]).
      CONCLUSION: Even when controlling for demographic risk, several family factors
      and one child factor place children at risk for PI. Clinicians may choose to use
      these as indicators for injury prevention counseling. Research on family effects
      may help clarify means to protect children who are demographically at risk for
      PI.

PMID- 8545222
TI  - How safe are day care centers? Day care versus home injuries among children in
      Norway.
AB  - OBJECTIVES: The study's objective was to examine and compare injury rates of
      children ages 6 months to 6 years in day care centers and homes. More
      specifically, we tested the hypothesis that the injury rate is lower in day care
      centers than at homes, as suggested by previous studies. METHODS: A comprehensive
      prospective injury registration was carried out in Stavanger, Norway, during
      1992. We obtained data from this system to identify injuries occurring in day
      care centers, homes, and other places during 1992. Exposure-adjusted incidence
      rates were calculated to compare the risk of injury at day care centers, homes,
      and other places. We also obtained data from medical records on use and costs of
      medical care. In addition, a parent questionnaire was developed and used to
      gather data on the amount of injury-related restricted activity. RESULTS: Among
      9454 children ages 6 months to 6 years in Stavanger, 770 injuries occurred during
      1992: 96 in day care centers, 472 at home, and 202 at other places. For children
      ages 6 months to 2 years, the rate of injuries was significantly lower in day
      care centers than at home (1.2 and 2.5, respectively, per 100,000 children
      hours), but for children ages 3 to 6, the rates of injuries were similar in day
      care centers and at home (1.3 and 1.5, respectively, per 100,000 children-hours).
      The great majority of children attending day care centers were from 3 to 6 years
      of age. No significant differences were found in the severity of the injuries.
      CONCLUSIONS: For children ages 3 to 6 years, which included most of the children
      attending day care centers in Stavanger, Norway, day care centers were not found
      to be safer than homes. We think continuing attention should be paid to injury
      control in day care centers.

PMID- 8545223
TI  - Surfactant replacement therapy for meconium aspiration syndrome.
AB  - OBJECTIVE: The pathophysiology of meconium aspiration syndrome (MAS) is related
      not only to mechanical obstruction of the airways and chemical injury to the
      respiratory epithelium but also to surfactant inactivation by meconium. A
      randomized, controlled study was performed to determine whether high-dose
      surfactant therapy improves the pulmonary morbidity of term infants ventilated
      for MAS. METHODS: Forty term infants receiving mechanical ventilation for MAS
      were enrolled in this trial, in which the infants in the study group (n = 20)
      received up to four doses of 150 mg (6 mL)/kg beractant (Survanta), instilled
      every 6 hours by continuous infusion for 20 minutes via a side hole endotracheal
      tube adapter, and the infants in the control group (n = 20) received 6 mL/kg air
      placebo. RESULTS: Mean arterial-to-alveolar PO2 ratio values increased from 0.09
      to 0.11 at 1 and 6 hours with a concomitant slight decrease in oxygenation index
      values from 23.7 to 19.7 at 1 hour and 20.7 at 6 hours after the first dose of
      surfactant. Oxygenation improved cumulatively after the second and third dose of
      surfactant, with mean arterial-to-alveolar PO2 ratios and oxygenation indices of
      0.18 and 12.1 at 6 hours after the second dose of surfactant and 0.31 and 5.9 at
      6 hours after the third dose of surfactant, eliminating the need for a fourth
      dose in any infant in the study group. After three doses of surfactant,
      persistent pulmonary hypertension had resolved in all but one of the infants in
      the study group versus none of the infants in the control group. No air leaks
      developed in any of the 20 infants in the study group after surfactant therapy,
      and only 1 infant required extracorporeal membrane oxygenation. Air leaks
      developed in 5 of the 20 infants in the control group, and 6 underwent
      extracorporeal membrane oxygenation. The duration of mechanical ventilation,
      oxygen therapy, and admission was significantly shorter in the surfactant group
      than in the control group. CONCLUSION: Surfactant replacement therapy, if started
      within 6 hours after birth, improves oxygenation and reduces the incidence of air
      leaks, severity of pulmonary morbidity, and hospitalization time of term infants
      with MAS.

PMID- 8545224
TI  - Changing levels of measles antibody titers in women and children in the United
      States: impact on response to vaccination. Kaiser Permanente Measles Vaccine
      Trial Team.
AB  - OBJECTIVES: In the United States, younger women are more likely to have immunity
      to measles from vaccination and are less likely to have been exposed to the wild
      virus than are older women. To evaluate changes in measles antibody titers in
      women in the United States and children's responses to measles vaccination, we
      analyzed data from a measles vaccine trial. METHODS: Sera collected from children
      before vaccination at 6, 9, or 12 months of age and from their mothers were
      assayed for measles antibodies by plaque reduction neutralization. Responses to
      vaccination with Merck Sharp & Dohme live measles virus vaccines at 9 months
      (Attenuvax) and 12 months (M-M-R II) were also analyzed. RESULTS: Among women
      born in the United States (n = 614), geometric mean titers (GMTs) of measles
      antibodies decreased with increasing birth year. For those born before 1957, 1957
      through 1963, and after 1963, GMTs were 4798, 2665, and 989, respectively. Among
      women born outside of the United States (n = 394), there were no differences in
      GMTs by year of birth. Children of younger women born in the United States were
      less likely than those of older women to be seropositive at 6, 9, or 12 months.
      The response to the vaccines varied by maternal birth year for children of women
      born in the United States. Among 9-month-old children, 93% of those whose mothers
      were born after 1963 responded, compared with 77% and 60% of those whose mothers
      were born in 1957 through 1963 and before 1957, respectively. Among 12-month-old
      children, 98% of those born to the youngest mothers responded, compared with 90%
      and 83% of those whose mothers were born in 1957 through 1963 and before 1957.
      The responses of children of women born outside of the United States were not
      associated with maternal year of birth. CONCLUSIONS: An increasing proportion of
      children in the United States will respond to the measles vaccine at younger ages
      because of lower levels of passively acquired maternal measles antibodies.

PMID- 8545225
TI  - Benefit of primary prophylaxis before 18 months of age in reducing the incidence
      of Pneumocystis carinii pneumonia and early death in a cohort of 112 human
      immunodeficiency virus-infected infants. New York City Perinatal HIV Transmission
      Collaborative Study Group.
AB  - OBJECTIVE: To determine the effectiveness of primary prophylaxis in preventing
      Pneumocystis carinii pneumonia (PCP) in children with perinatally acquired human
      immunodeficiency virus 1 (HIV-1) infection. METHODS: We conducted a retrospective
      analysis of a cohort of infants followed from birth at six metropolitan hospitals
      and one outpatient clinic for pregnant, drug-using women in New York City.
      Outcomes measured were histologically confirmed PCP and/or death. The potential
      confounding effect of the infant's stage of illness, as determined by CD4 count,
      was controlled by including all CD4 determinations as time-dependant covariates
      in a Cox proportional hazards analysis. Cases were censored at PCP onset, death,
      loss to follow-up, and 18 months of age. RESULTS: One hundred twelve HIV-infected
      children were enrolled at birth between 1986 and 1993. Sixty of these were
      tracked beyond 18 months of age; of the others, 21 died before this age, 4 were
      considered lost to follow-up, and 27 had not reached 18 months of age at the last
      visit. Only 3 cases (4%) of confirmed PCP occurred among the 70 children who
      received primary PCP prophylaxis before 18 months of age, compared with 12 cases
      (28%) among 42 children not receiving PCP prophylaxis at any point before 18
      months of age. The Kaplan-Meier estimated incidence of PCP in the first year
      among children not receiving prophylaxis was 25% (95% confidence interval [CI],
      12 to 39). Using Cox methods, the unadjusted risk of PCP among infants not
      receiving prophylaxis, relative to those receiving it, was 4.1 (95% CI, 1.1 to
      15); the relative risk was 4.4 (95% CI, 1.2 to 17) adjusting for the percentage
      of CD4-positive lymphocytes and 5.1 (95% CI, 1.3 to 20) adjusting for the
      absolute number of CD4-positive cells. Eight of 26 deaths were caused by PCP, and
      the likelihood of early death was significantly diminished if PCP prophylaxis was
      given (relative risk controlling for absolute CD4 cells, 2.57; 95% CI, 1.1 to
      6.1). CONCLUSIONS: We report evidence that primary antimicrobial PCP prophylaxis
      is highly effective in decreasing the frequency of PCP and early death in infants
      with perinatal HIV infection. These findings support the revised National
      Pediatric HIV Resource Center and Centers for Disease Control and Prevention
      guidelines for PCP prophylaxis in children.

PMID- 8545226
TI  - Physician experience with pediatric inpatient care in Washington State.
AB  - OBJECTIVE: To determine the frequency with which pediatricians and family
      physicians in Washington State serve as attending physicians for pediatric
      inpatients. DESIGN: Retrospective review of statewide hospital discharge data.
      SUBJECTS: Attending physicians for all patients younger than 18 years of age with
      nonsurgical diagnoses discharged from civilian hospitals in Washington State
      during 1989 and 1990. RESULTS: Using medical rosters, the self-identified
      specialty of the attending physician was determined for 93% (n = 181,581) of
      discharges. Pediatricians and family physicians were listed as attending for 61%
      and 28%, respectively, of all eligible patients. Statewide, 97% (n = 555) of all
      pediatricians and 86% (n = 939) of all family physicians served as attending
      physicians for at least one inpatient, including healthy newborns, during the 2
      year study period. The median annual number of discharges per physician was 78
      for pediatricians and 14.5 for family physicians. Excluding healthy newborns, the
      median annual number of discharges was 25 for pediatricians and 3 for family
      physicians. Five percent of the physician attending group provided inpatient care
      for 50% of all children hospitalized with diagnoses other than healthy newborn;
      50% of attending physicians cared for 95% of the patients. In rural hospitals,
      where family physicians served as attending physicians for 44% of pediatric
      inpatients, children were 3.3 times more likely to receive their care from family
      physicians than those hospitalized in urban centers. CONCLUSIONS: Most
      pediatricians and family physicians serve as inpatient attending physicians for
      hospitalized children only infrequently. These findings question whether the
      emphasis on inpatient care in many pediatric and family medicine training
      programs remains an appropriate goal.

PMID- 8545227
TI  - Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines-
      report of the National Multicenter Trial. United States Rotavirus Vaccine
      Efficacy Group.
AB  - OBJECTIVE: Rotavirus is a leading cause of morbidity and mortality from
      dehydrating gastroenteritis in infants and young children worldwide. Virtually
      every child is infected by age 4 years, justifying universal childhood
      immunization when a safe and effective vaccine is available. We report the
      results of a multicenter, placebo-controlled field trial in the United States of
      monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus
      vaccines (RRVs). DESIGN: In this randomized, double-blind trial, 1278 healthy
      infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV,
      or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x
      10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and
      severity was graded throughout one rotavirus season. Two stool specimens per
      episode were tested for rotavirus. RESULTS: The incidence of reactions did not
      differ among treatment groups during the 5-day, postvaccination safety
      surveillance period for any of the three doses. Both vaccines significantly
      reduced the incidence of rotavirus gastroenteritis. Vaccination was most
      protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus
      episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness.
      Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total
      episodes of gastroenteritis of all causes and an 82% reduction in all cases of
      dehydrating diarrhea. CONCLUSION: RRV-TV is highly protective against very
      severe, dehydrating rotavirus gastroenteritis.

PMID- 8545228
TI  - Research in pediatric residency programs.
AB  - BACKGROUND AND OBJECTIVES: We have required residents in pediatrics at the
      Cleveland Clinic Foundation to give research presentations since 1989; this
      article reviews our experience with this program. Additionally, we sought to
      determine how many other accredited pediatric programs in the United States also
      require this. METHODS: Retrospective review of the Cleveland Clinic program;
      descriptive statistics of other United States residency programs, obtained by
      questionnaire. RESULTS: Pediatric residents at the Cleveland Clinic have given
      108 research presentations since 1989, and have developed 33 (30.5%) of them into
      manuscripts or abstracts. We mailed questionnaires to 215 pediatric residency
      program directors and received responses from 177 (82%). Of these, 48 (27%)
      indicated their programs had a research requirement; residents could present
      their findings in departmental meetings or submit an abstract or manuscript to a
      professional society or journal. Respondents cited several barriers to research:
      residents are too busy, there are too few faculty members to mentor them,
      financial resources are limited, and there is no residency review committee
      requirement. CONCLUSIONS: Even though only approximately one fourth of the
      pediatric residency programs in the United States require research, we feel it is
      worthwhile experience. Despite barriers, residents can and do perform research
      and publish their findings.

PMID- 8545229
TI  - Relationship between blood lead and nutritional factors in preschool children: a
      cross-sectional study.
AB  - OBJECTIVE: The purpose of this study was to assess the relationships between
      selected nutritional factors and blood lead levels of preschool children.
      METHODOLOGY: Data on 296 children, aged 9 to 72 months, who were cared for at the
      University of Maryland at Baltimore Pediatric Ambulatory Center were examined in
      this cross-sectional study. Nutritional status, socioeconomic aspects, medical
      history, and potential sources of lead exposure were assessed. Blood samples were
      evaluated for levels of blood lead, serum iron (ferritin), free erythrocyte
      photoporphyrin, calcium, and hematocrit. RESULTS: The average blood lead level
      was 11.4 micrograms/dL. Multicollinearity of nutritional factors was addressed
      using regression techniques. After adjusting for confounders, significant
      positive associations with blood lead were found for total caloric intake (P =
      .01) and dietary fat (P = .05). CONCLUSIONS: The findings of this study suggest
      that even when behavioral and environmental exposures to lead were statistically
      controlled, total caloric intake and dietary fat each had an independent and
      significant association with the level of blood lead.

PMID- 8545230
TI  - Identification of children at risk for lead poisoning: an evaluation of routine
      pediatric blood lead screening in an HMO-insured population.
AB  - OBJECTIVES: To estimate the prevalence of elevated blood lead levels in children
      receiving well-care checkups; and to evaluate the effectiveness of certain key
      risk factors in detecting children at higher risk for elevated blood lead levels.
      DESIGN: Cross-sectional study. SETTING: Two facilities of the Kaiser Permanente
      Medical Care Program (KPMCP) health maintenance organization (HMO), northern
      California region. PATIENTS: Six hundred thirty-six children, aged 12 to 60
      months, who were seen at four KPMCP facilities in two subregions for a well-care
      checkup from September 1991 through August 1992. INTERVENTIONS: Blood samples
      were collected from each child and analyzed for lead content. Participating
      parents completed a questionnaire that included questions recommended by the
      Centers for Disease Control and Prevention (CDC) about the child's and the
      parents' lead exposure via home, workplace, and hobbies. RESULTS: Ninety-six
      percent of the children had blood lead levels under 10 micrograms/dL. Blood lead
      levels declined with increasing age and were higher for black children compared
      with whites. Age of residential housing, mother's education, and residence in an
      old house with peeling paint had low sensitivity and positive predictive value
      for identifying children with blood lead levels over 10 micrograms/dL.
      CONCLUSION: Universal routine screening for elevated blood lead levels in
      children in an employed, HMO-insured population is not warranted on grounds of
      prevalence. Responses to CDC questions do not effectively identify high-risk
      children in this population.

PMID- 8545231
TI  - Lead poisoning risk determination in a rural setting.
AB  - OBJECTIVES: To determine the prevalence of elevated blood lead levels among
      children living in a rural area and to determine the effectiveness of the Centers
      for Disease Control and Prevention (CDC) Lead Risk Assessment Questionnaire and
      additional questionnaire items in correctly identifying rural children having
      elevated blood lead levels. RESEARCH DESIGN: Comparison of results of a
      questionnaire that is intended to identify children as being at low or high risk
      for lead poisoning with children's blood lead levels. SETTING: The three practice
      sites of the only pediatric group in a rural county of upstate New York.
      PATIENTS: A consecutive sample of 705 children ages 6 to 72 months who were seen
      for health supervision visits between June and September 1993. RESULTS: Sixty
      nine percent of the children were considered to be at high risk for lead
      poisoning by the CDC questionnaire. Overall, 8.4% of the children in the study
      had blood lead levels of 10 micrograms/dL (0.48 mumol/L) or higher, and 2.1% had
      blood lead levels of 15 micrograms/dL (0.72 mumol/L) or higher. No significant
      difference was noted between the percentages of high- and low-risk children who
      had elevated blood lead levels. To devise a more effective lead risk assessment
      tool for children in this setting, the two items from the CDC questionnaire and
      the two additional items that had the greatest predictive utility were combined
      to form a short alternative questionnaire. The alternative questionnaire thus
      consisted of items concerning whether the child has a sibling or playmate with
      lead poisoning, whether the child lives near an industry that potentially may
      release lead, whether the child lives in rented or owner-occupied housing, and
      whether the child has a parent who is a migrant farm worker. Children categorized
      as high risk with the alternative questionnaire were much more likely to have
      elevated blood lead levels than those who were categorized as low risk. The
      alternative questionnaire was very effective in correctly identifying children
      with elevated blood lead levels. Eighty-eight percent of children having blood
      lead levels of 10 micrograms/dL or higher and 100% of children having blood lead
      levels of 15 micrograms/dL or higher were classified as high risk by the
      questionnaire. Children classified as low risk were very unlikely to have
      elevated blood lead levels; 98% of low-risk children had blood lead levels of
      less than 10 micrograms/dL, and 100% had blood lead levels of less than 15
      micrograms/dL. CONCLUSIONS: These results suggest that the CDC lead risk
      assessment questionnaire is of limited benefit in identifying rural children with
      blood lead levels 10 micrograms/dL or higher or 15 micrograms/dL or higher. An
      alternative questionnaire, however, seems to have marked clinical utility for
      identifying rural children with elevated blood lead levels.

PMID- 8545232
TI  - Nephrocalcinosis is associated with renal tubular acidosis in children with X
      linked hypophosphatemia.
AB  - BACKGROUND: X-linked hypophosphatemia is characterized clinically by rickets and
      growth retardation. Therapy of this disorder with phosphate and vitamin D often
      produces nephrocalcinosis. The long-term effects of nephrocalcinosis on renal
      function in patients with X-linked hypophosphatemia are unknown. The purpose of
      this study was to evaluate the prevalence of glomerular and tubular disorders in
      patients with X-linked hypophosphatemia who developed nephrocalcinosis. METHODS:
      The creatinine clearance and the prevalence of renal tubular acidosis were
      compared in 19 patients with X-linked hypophosphatemia and nephrocalcinosis with
      15 patients with X-linked hypophosphatemia without nephrocalcinosis. RESULTS:
      Sixteen of the 19 patients (84%) with nephrocalcinosis had a hyperchloremic
      metabolic acidosis compared with one of the 13 patients without nephrocalcinosis
      (P < .01). The serum bicarbonate of patients with nephrocalcinosis was 20.0 +/-
      0.7 as compared to 24.5 +/- 0.6 mmol/L in patients without nephrocalcinosis (P <
      .01). The urinary anion gap was positive in all patients with acidosis (+62.1 +/-
      13.3 mmol/L). The creatinine clearance was 125 +/- 6 mL/min/1.73 m2 in patients
      with nephrocalcinosis and 124 +/- 7 mL/min/1.73 m2 in those without
      nephrocalcinosis. CONCLUSION: Therapy of X-linked hypophosphatemia is often
      associated with nephrocalcinosis. Nephrocalcinosis is associated with renal
      tubular acidosis in patients with X-linked hypophosphatemia.

PMID- 8545233
TI  - Self-efficacy in pediatric resuscitation: implications for education and
      performance.
AB  - OBJECTIVE: This article examines the relevance of self-efficacy--a cognitive
      process indicating people's confidence in their ability to effect a given
      behavior--to training and performance of pediatric resuscitation. The case is
      made that self-efficacy is likely to influence the development of and real-time
      access to cognitive, affective, psychomotor, and social aspects of resuscitation
      proficiency. METHODS: Comprehensive literature reviews were conducted on relevant
      topic areas, including self-efficacy theory and empirical investigations of self
      efficacy in clinical practice. Three case studies are used to illustrate the
      influence of self-efficacy on resuscitation practice. RESULTS: The limited
      empirical evidence on the role of self-efficacy in clinical practice is
      consistent with self-efficacy theory: clinicians are less likely to initiate and
      sustain behaviors for which they lack confidence. This performance-based
      confidence can be distinguished from both  knowledge and skills necessary to
      perform the behavior. CONCLUSIONS: Even clinicians who are knowledgeable and
      skilled in resuscitation techniques may fail to apply them successfully unless
      they have an adequately strong belief in their capability. General guidelines for
      promoting self-efficacy are presented, and specific recommendations are made for
      enhancing resuscitation self-efficacy during resuscitation training and
      postresuscitation procedures.

PMID- 8545234
TI  - Synthesis of two peptide scorpion toxins and their use to investigate the aortic
      tissue regulation.
AB  - The 37 amino acid residue polypeptides iberiotoxin and charybdotoxin, which
      contain three disulfide bridges, were chemically synthesized and characterized.
      The physiological effectiveness of these peptides was tested on rabbit aorta in
      vitro.

PMID- 8545235
TI  - Structure-activity relationships for Periplaneta americana hypertrehalosemic
      hormone. I: The importance of side chains and termini.
AB  - Single amino acid replacement analogues for the native hypertrehalosemic hormone
      I of the American cockroach, Periplaneta americana (Pea-CAH-I: pGlu-Val-Asn-Phe
      Ser-Pro-Asn-Trp-NH2), have been prepared by solid-phase peptide synthesis, and
      complete dose-response curves have been measured in P. americana monitoring the
      carbohydrate-mobilizing activity in vivo. All analogues that elicited
      hypertrehalosemia showed similar time-response courses, indicating that transport
      and degradation rates were comparable. Comparison of the potency and efficacy
      parameters of the analogues under study in the dose-response curves revealed four
      activity groups: 1) analogues that had the aromatic amino acids at positions 4
      (phenylalanine) or 8 (tryptophan) replaced by alanine and glycine, respectively,
      had trace activity; 2) analogues with alanine at positions 1 or 2 had low
      potencies and an apparent biphasic dose-response relationship without much
      observable loss of efficacy; 3) analogues with glycine at positions 6 and 7 had
      potencies and efficacies most similar to Pea-CAH-I; and 4) analogues that had
      either an alanine instead of asparagine residue at position 3, or had a
      substitution of the carboxylamide function at the C-terminus by a carboxyl
      function reached apparent saturation, but only achieved 50-57% of the maximum
      activity of the native peptide. The potency profile for the analogue set is
      consistent with the importance of the N-terminal pentapeptide and the C-terminal
      tryptophan interacting with receptor(s) more closely than the side chains at
      positions 6 and 7, which are predicted to be the corner residues of a beta-turn.
      Finally, the biphasic dose-response curves observed for more than one analogue
      suggest the potential that receptors for Pea-CAH-I exist in more than one form.

PMID- 8545236
TI  - A single receptor transduces both inhibitory and stimulatory signals of FMRFamide
      related peptides.
AB  - In the oviduct of Locusta migratoria, an inhibitory neuropeptide, PDVDHVFLRFamide
      (SchistoFLRFamide) has separate binding and activation regions. VFLRFamide is the
      minimum sequence required for binding, which is comparable to the parent peptide,
      whereas the His residue, which does not contribute to binding, is a critical
      amino acid for the inhibitory activity of the receptor. In this study, the His
      residue of HVFLRFamide was substituted by Tyr, Leu, Ile, or Val to yield a group
      of HVFLRFamide analogues. As revealed by bioassay, all of these hexapeptide
      analogues exert stimulatory effects on oviduct muscle contraction. However,
      results from three sets of binding experiments indicate that these stimulatory
      FMRFamide-related peptides (FaRPs) share the same binding site as PDVDHVFLRFamide
      and HVFLRFamide, the inhibitory FaRPs. First, unlabeled stimulatory FaRPs
      competitively displace bound [125I]YDVDHVFLRFamide. Second, two binding sites for
      the stimulatory peptide YVFLRFamide were identified and both of them have similar
      binding affinities and maximum binding capacities as the two binding sites for
      PDVDHVFLRFamide. Third, unlabeled PDVDHVFLRFamide and HVFLRFamide competitively
      displace the bound [125I]YVFLRFamide in the same manner as unlabeled YVFLRFamide.
      These findings suggest the presence of a novel ligand-receptor reaction system.
      In this system, inhibitory peptides and stimulatory peptides share a single
      receptor by having the same binding sequence VFLRFamide, but are able to produce
      opposite muscle responses due to differences in activation sites.
      Correspondingly, this single receptor could be coupled with two different
      intracellular signaling systems to mediate either inhibitory or stimulatory
      responses.

PMID- 8545237
TI  - Distribution of FMRFamide-like immunoreactivity in the brain of the lungfish
      Protopterus annectens.
AB  - The distribution of FMRFamide-like immunoreactive peptides was studied in the
      brain of the African lungfish, Protopterus annectens, using the indirect
      immunofluorescence technique. The main populations of FMRFamide-positive cell
      bodies were detected in the forebrain and in the mesencephalic tegmentum. In the
      telencephalon, only a small number of FMRFamide-immunoreactive neurons was
      localized at the level of the subpallium, in the nucleus septi medialis. The
      diencephalon contained two prominent groups of FMRFamide-positive cell bodies
      located in the preoptic and periventricular preoptic nuclei. The thalamus
      exhibited only scattered FMRFamide-immunoreactive perikarya in its ventral part.
      In the mesencephalon, a group of positive cell bodies was identified in the
      caudal region of the tegmentum. A strong immunoreaction was also detected in the
      nervus terminalis. In the pituitary, most of the cells of the intermediate lobe
      were brightly stained. FMRFamide-like immunoreactive fibers and nerve terminals
      were widely distributed in the brain. In the telecephalon, numerous fibers were
      observed in several regions of the pallium and subpallium. A dense plexus of
      fibers was found in the hypothalamus and the thalamus. Immunoreactive fibers were
      seen coursing along the ventral wall of the infundibular cavity and terminating
      in the pars nervosa of the pituitary. The tectum and the ventral mesencephalon
      were also densely innervated. In contrast, the caudal brainstem only showed
      scarce immunoreactive processes. Coexistence of FMRFamide- and neuropeptide Y
      like immunoreactivity was observed in the preoptic nucleus and in the nervus
      terminalis. The widespread distribution of FMRFamide-immunoreactive neurons in
      the brain and pituitary of P. annectens suggests that the peptide may exert both
      neuromodulator and neuroendocrine functions. The similarity between the
      distribution patterns of FMRFamide and neuropeptide Y in the brain of lungfish
      and amphibians supports the concept of a close phylogenetic link between these
      two groups.

PMID- 8545238
TI  - Preoptic recess ablation selectively increases baroreflex sensitivity to
      angiotensin II in conscious rats.
AB  - Angiotensin II (ANG II) attenuates baroreflex sensitivity through central
      pathways. However, the specific CNS sites where ANG II inhibits baroreflexes are
      not completely understood. The periventricular tissue of the anteroventral third
      cerebral ventricle (AV3V) mediates several responses to centrally and
      peripherally administered ANG II. Therefore, these studies determined the effects
      of bilateral electrolytic ablation of AV3V periventricular tissue on reflex
      induced changes in heart rate during pressor and depressor responses evoked by IV
      administration of phenylephrine (PE), ANG II, and nitroprusside (NP). Animals
      were prepared with catheters in the femoral artery and vein 10-14 days following
      AV3V ablation or control (CONT) surgery. The following day, baroreflex
      sensitivity in the conscious animals was evaluated as the slope of the regression
      line relating blood pressure and heart rate during IV infusion (1 min) of three
      doses of PE, ANG II, and NP. Baroreflex sensitivity during PE and NP infusion
      were equivalent in AV3V-lesioned and CONT animals. However, animals with AV3V
      lesions demonstrated significantly greater baroreflex sensitivity during ANG II
      infusion than both PE-treated AV3V-lesioned animals and ANG II-treated CONT
      animals. These data suggest that the impairment of baroreflex-induced bradycardia
      during pressor responses evoked by ANG II is mediated by tissue located in the
      AV3V region.

PMID- 8545239
TI  - Glycyl-histidyl-lysine interacts with the angiotensin II AT1 receptor.
AB  - Gly-His-Lys, a tripeptide isolated from human plasma that increases the growth
      rate of many cells, stimulated in dose-dependent fashion the activity of
      phosphorylase a in isolated rat hepatocytes. Such effect was associated to
      increases in both IP3 production and [Ca++]i. Interestingly, these effects of Gly
      His-Lys were antagonized by losartan, a nonpeptide angiotensin II receptor
      antagonist (AT1 selective), which suggested that these receptors were involved in
      its effect. Binding competition experiments using the radioligand [125I][Sar1
      Ile8]angiotensin II clearly indicated that Gly-His-Lys interacts with AT1
      receptors. It was also observed that other histidine-containing tripeptides were
      also capable of interacting with these receptors.

PMID- 8545241
TI  - In vitro stability of some reduced peptide bond pseudopeptide analogues of
      dynorphin A.
AB  - Eight analogues of DYN A(1-11)-NH2 incorporating the nonhydrolyzable psi [CH2-NH]
      peptide bond surrogate were tested for their in vitro enzymatic stability in
      mouse brain homogenates. Results show that the Leu(5)-Arg6 and to a lesser extent
      the Arg(7)-Ile8 and Ile(8)-Arg9 peptide bonds are the more susceptible to
      enzymatic cleavage in the native peptide. (Leu5 psi[CH(2)-NH]Arg6)DYN A(1-11)-NH2
      exhibits an almost complete resistance to enzymatic cleavage with a half-life
      greater than 500 min in brain, compared to 42 min for the standard peptide, DYN
      A(1-11)-NH2.

PMID- 8545240
TI  - Effect of Met-enkephalin and opioid antagonists on rat macrophages.
AB  - Effects of Met-enkephalin (Met-ENK) and opioid antagonists on H2O2 release by
      peritoneal macrophages from DA and AO rats were investigated. Met-ENK increased
      and decreased H2O2 production by macrophages of DA and AO rats, respectively.
      These effects were antagonized by low, but not high, concentrations of naloxone
      and ICI 174864. High concentrations of both antagonists directly modulated H2O2
      release and retained the strain-related differences seen with Met-ENK. The
      results showed direct, strain- and dose-dependent, effects of Met-ENK, naloxone,
      and ICI 174864 on rat macrophage function.

PMID- 8545242
TI  - Methionine-enkephalin-Arg-Phe immunoreactivity in heart tissue.
AB  - Previous findings of enkephalins in cardiac tissue led us to investigate
      enkephalin distribution in animal models used for cardiovascular research. Canine
      cardiac methionine-enkephalin (ME) concentrations are low and evenly distributed
      between atria (4.2 +/- 0.6 fmol/mg protein, n = 30) and ventricles (4.4 +/- 0.5).
      In contrast, methionine-enkephalyl-arginyl-phenylalanine (MEAP) immunoreactivity
      (IR) is higher and preferentially concentrated in the ventricle (112 +/- 12) vs.
      the atria (23.2 +/- 2.6 fmol/mg protein). HPLC analysis suggests the
      atrial/ventricular difference is partly due to altered posttranslational
      processing. Nearly 90% of ventricular IR is comprised of MEAP (46%) and peptide B
      (40%) whereas these peptides represent less than half of the atrial content. A
      nonneuronal localization is indicated because the peptide distribution does not
      correspond to the catecholamine distribution. Canine left ventricular tissue
      sections were processed for immunohistochemistry with the MEAP antibody.
      Fluorescence was distributed throughout the myocytes and concentrated in ordered
      lines perpendicular to the myocyte longitudinal axis corresponding to the area of
      the intercalated disc. This suggests opioids may be important in communication
      between cardiomyocytes, and possibly the presence of a unique peptide secretory
      mechanism utilizing the intercalated disc. The relative peptide content in cat
      and pig hearts was similar to the dog; however, the distribution was different.
      Feline cardiac ME content was distributed 2:1 in favor of the ventricles and
      corresponded with a preferential ventricular norepinephrine distribution. The
      MEAP-IR pattern gave a ventricular/atrial ratio lower (3.5:1) in cat heart vs.
      dog (5:1). In contrast, pig heart ME and MEAP-IR ventricular/atrial ratios were
      reversed for both ME (1:10) and MEAP (1:2). HPLC of pig left ventricle showed
      that MEAP and peptide B represented 33% and 39% of the MEAP-IR, respectively.
      These species variations may correlate to the differences observed in cardiac
      function.

PMID- 8545243
TI  - Involvement of different subtypes of cholecystokinin receptors in opioid
      antinociception in the mouse.
AB  - Various doses of sulfated cholecystokinin octapeptide (CCK-8s) injected
      intracerebroventricularly (ICV) alone did not show any antinociceptive effect.
      CCK-8s (0.01-1 ng) pretreated ICV for 10 min dose-dependently attenuated the
      inhibition of the tail flick response induced by ICV-administered morphine (2
      micrograms). beta-endorphin (1 microgram), and U50,488H (trans-3,4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzeocetamide), 60 micrograms). However,
      ICV pretreatment with CCK-8s was not effective in reducing the inhibition of the
      tail flick response induced by [D-Pen(2)-D-Pen5]enkephalin (DPDPE; 10 micrograms)
      administered ICV. To determine what subtype(s) of CCK receptors are involved in
      antagonizing the antinociception induced by these opioids, effect of lorglumide
      sodium salt (a CCKA receptor antagonist) or PD135,158 N-methyl-D-glucamine salt
      (a CCKB receptor antagonist) on opioid-induced inhibition of the tail flick
      response was examined. Various doses of lorglumide sodium salt (lorglumide) or
      PD135,158 N-methyl-D-glucamine salt (PD135,158) injected ICV alone did not affect
      the basal tail flick response. The antagonistic effect of CCK-8s on morphine-,
      beta-endorphin-, and U50,488H-induced inhibition of the tail flick response was
      blocked in a dose-dependent manner by the co-ICV injection of PD135,158 (0.001
      0.1 ng). The co-ICV injection of lorglumide (0.001-0.1 ng) dose-dependently
      blocked the antagonistic effect of CCK-8s on beta-endorphin- and U50,488H
      induced, but not morphine-induced, inhibition of the tail flick response. Our
      results suggest that both CCKA and CCKB receptors are involved in antagonizing
      antinociception induced by beta-endorphin and U50,488H administered
      supraspinally. However, only CCKB (but not CCKA) receptors are involved in
      antagonizing antinociception induced by morphine administered supraspinally. CCK
      receptors are not involved in antagonizing the supraspinally administered DPDPE
      induced antinociception.

PMID- 8545244
TI  - Changes in CNS neuropeptide FF-like material, pain sensitivity, and opiate
      dependence following chronic morphine treatment.
AB  - Tolerance and dependence to opiates may be an adaptive process that limits
      excessive effects of morphine on the CNS. Because no consistent opiate receptor
      reduction in chronically treated rats seems to underlie the hyposensitivity to
      morphine, an alternative hypothesis has postulated a role of "antiopioid"
      peptides. It is possible to speculate that the administration of morphine
      stimulates antiopioid systems such as neuropeptide FF (NPFF), as part of an
      homeostatic mechanism contributing to the development of tolerance. To test this
      hypothesis, pain sensitivity, opiate dependence, and CNS NPFF-IR levels were
      estimated at different times after implantation of morphine pellets (2 x 75 mg;
      NIDA). Three hours after morphine pellet treatment the analgesic effect was
      maximum and it decreased rapidly during the following 12 h. Naloxone-precipitated
      withdrawal syndrome was detected as soon as 3 h after morphine pellet
      implantation and was maximal after 24 h. NPFF-IR levels were measured in the
      spinal cord, brain stem, and hypothalamus. A significant decrease of NPFF-IR was
      observed 1 h after morphine pellet implantation (-25% to -45% depending on the
      structures) followed by a drastic increase of NPFF-IR levels (+60 to +140%)
      between 3 and 6 h. NPFF-IR levels rapidly returned to baseline after 24-36 h. It
      is suggested that the activity of these NPFF-IR neurones may increase gradually
      as a consequence of the continuous stimulation of opiate receptors and be part of
      an adaptive process that is able to counteract morphine effects and to induce
      dependence and tolerance to the analgesic effects of opiates.

PMID- 8545245
TI  - Excitatory action of [Leu13]motilin on the gastrointestinal smooth muscle
      isolated from the chicken.
AB  - The effects of a porcine motilin analogue, [Leu13]motilin (LMT) on the smooth
      muscle preparations isolated from the chicken gastrointestinal (GI) tract were
      investigated in vitro. In the proventriculus, LMT (100 nM to 30 microM) caused an
      atropine-sensitive contraction and enhanced the electrical field stimulation
      (EFS)- or 1,1-dimethyl-4-phenyl-piperazinium (DMPP)-induced contraction without
      affecting the response to acetylcholine (ACh). LMT also caused a concentration
      dependent contraction of the intestinal tract (duodenum, jejunum, ileum, and
      colon). The responsiveness to LMT was strongest in the jejunum and weakest in the
      colon. The responses to LMT in the intestinal segments were not affected by
      tetrodotoxin, atropine, hexamethonium, pyrilamine, spantide, and 5
      hydroxyltryptamine-induced desensitzation, but significantly decreased by
      verapamil or removal of external Ca2+. LMT did not enhance the EFS- or DMPP
      induced contraction in the ileum. Canine motilin also contracted the intestinal
      segments in a similar concentration range to LMT with an equal potency, but
      erythromycin A (EMA) and N-ethyl-N-demethyl-8,9-anhydroerythromycin A, 6-9
      hemiketal (EM523) showed only a weak contractile activity even at high
      concentration (up to 100 microM), indicating that motilin receptors in the
      chicken intestine were somewhat different from those of mammals. In conclusion,
      LMT produces an excitatory response in the chicken GI tract with a different
      sensitivity from region to region. The mechanisms of the action were different
      between the proventriculus and small intestine; that is, LMT contracts the small
      intestine through the direct action on the smooth muscle cells, but this peptide
      acts on the enteric cholinergic neurones and stimulates ACh release, and thus
      regulates autonomic neuroeffector transmission in the proventriculus.

PMID- 8545246
TI  - Pancreatic polypeptide and splanchnic blood flow in anesthetized rats.
AB  - The aim of the study was to evaluate the effects of pancreatic polypeptide (PP)
      on splanchnic blood flow in anesthetized rats. For this purpose, either PP
      dissolved in saline (225, 450, or 900 pmol/kg body weight/h) or saline alone was
      infused at a rate of 2 ml/h for 30 min. Immediately after the infusion the blood
      flow to the whole pancreas, islets, duodenum, and colon was measured with a
      microsphere technique. The highest dose of PP caused a small decrease in mean
      arterial blood pressure. The two lowest doses decreased duodenal blood flow, but
      did not affect the blood perfusion to the other investigated organs. The highest
      dose of PP decreased the blood flow to the pancreas, islets, and duodenum, did
      not affect colonic blood flow. No change in the fraction of whole pancreatic
      blood flow diverted through the islets could be seen after PP administration. It
      is concluded that administration of high doses of PP induces a general splanchnic
      vasoconstriction.

PMID- 8545247
TI  - CGRP antagonists enhance gastric acid secretion in 2-h pylorus-ligated rats.
AB  - The influence of calcitonin gene-related peptide (CGRP) antagonists on gastric
      acid secretion was investigated in rats. Intravenous injection of the CGRP
      receptor antagonist, CGRP(8-37) (128 nmol/kg) or the CGRP antibody #4901 (4.8
      mg/kg, IV) completely prevented alpha-CGRP (3.9 nmol/kg/h)-induced inhibition of
      acid response to pentagastrin in urethane-anesthetized rats with gastric fistula.
      CGRP antibody (4.8 mg/kg, IV) increased by 93% gastric acid secretion in
      conscious rats with pylorus ligation for 2 h. (CGRP(8-73) (128 nmol/kg, IV) also
      enhanced the acid response measured 2 h after pylorus ligation in conscious rats
      and in urethane-anesthetized rats infused with pentagastrin by 91% and 56%,
      respectively. These results suggest that endogenous CGRP attenuates the gastric
      acid response measured 2 h after pylorus ligation.

PMID- 8545248
TI  - Nitric oxide is involved in the ACTH-induced behavioral syndrome.
AB  - In many animal species, the ICV injection of ACTH and of several shorter
      sequences of the ACTH molecule (melanocortin peptides) induces a peculiar
      behavioral syndrome mainly characterized by excessive grooming and by repeated
      acts of stretching and yawning. In adult males, spontaneous penile erections with
      ejaculation are also induced. We have studied the effect of NO synthase
      inhibition on this behavioral syndrome. The IP injection of the NO synthase
      inhibitor L-NG-nitroarginine methyl ester (NAME) significantly prevented--at the
      doses of 50 and 100 mg/kg--all the behavioral symptoms induced by the ICV
      administration of ACTH(1-24) (4 micrograms/rat). On the other hand, the ICV
      injection of NAME (up to 300 micrograms/rat) had no influence on the ACTH-induced
      excessive grooming and stretching, while significantly inhibited the display of
      yawnings and penile erections. These data indicate that brain NO synthase is
      involved in the mechanism of ACTH-induced yawning and penile erections, whereas
      peripheral NO synthase is involved in the induction of stretching and grooming.

PMID- 8545249
TI  - Immunocytochemical localization and biochemical characterization of melanotropin
      like peptides in the gonads of a protochordate.
AB  - The compound gonads of the protochordate ascidian Styela plicata were
      investigated by immunocytochemistry, HPLC, and radioimmunoassay to verify the
      presence of melanotropin-like peptides, alpha-MSH-like immunoreactivity is
      localized in the follicular cells and in the perinuclear cytoplasm of different
      types of ovaric follicles, as well as in the spermatogonia and spermatocytes of
      testicular lobules. The ascidian immunoreactive peptides occurring in the gonads
      consist of alpha-MSH and ACTH(1-13)-NH2 and their amounts are higher in summer
      than in winter.

PMID- 8545250
TI  - Activation of adenylate cyclase and phosphodiesterase inhibition enhance neutral
      endopeptidase activity in human endothelial cells.
AB  - Endothelial neutral endopeptidase (EC 3.4.24.11, NEP) contributes to the
      inactivation of vasoactive and inflammatory peptides such as f-Met-Leu-Phe,
      substance P, atrial natriuretic peptide, and bradykinin. The aim of the present
      study was to investigate the cellular regulation of NEP expression in human
      endothelial cells, focusing on the role of cyclic nucleotides and cellular
      phosphodiesterases (PDE). Activation of adenylate cyclase by forskolin or
      prostaglandin E1 (PGE1) induced an increase of NEP activity and NEP protein after
      24 h of incubation. This effect was mimicked by two activators of protein kinase
      A, dibutyryl-cAMP and 8-bromo-cAMP. The nonspecific PDE inhibitor, 3-isobutyl-1
      methylxanthine (200 microM), increased NEP activity up to 192%. The activator of
      guanylate cyclase, sodium nitroprusside (SNP), did not affect NEP activity but
      completely inhibited the 3-isobutyl-1-methylxanthine-mediated increase of NEP
      activity. The PDE-III inhibitors motapizone (100 microM) and enoximone (100
      microM) enhanced NEP activity up to 188% and 213%, the PDE-IV inhibitor rolipram
      (3 microM) up to 162%, and the combined PDE-III/IV inhibitor zardaverine (1
      microM) up to 176% of control values. The present data provide evidence for a
      cAMP-mediated increase of NEP activity in human endothelial cells.

PMID- 8545251
TI  - Binding of the nonpeptide antagonist, SB 209670, to endothelin receptors on
      cultured neurons.
AB  - We studied the binding characteristics of a novel, nonpeptide endothelin
      antagonist, SB 209670, to two subtypes of endothelin (ET) receptor in cultured
      rat cerebellar granule cell neurons. Displacement binding studies of [125I]ET-1
      performed in the presence of the ETB receptor-selective agonist, sarafotoxin 6c
      (S6c), allowed us to measure a Ki of 4.0 +/- 1.5 nM for (+/-)SB 209670 at the ETA
      receptor (n = 4). Similarly, binding studies in the presence of the ETA receptor
      selective antagonist, BQ123, allowed us to measure a Ki of 46 +/- 14 nM for (+/
      )SB 209670 at the ETB receptor (n = 4). These studies indicate that the novel
      endothelin antagonist, SB 209670, has high affinity for both types of neuronal
      endothelin receptor.

PMID- 8545252
TI  - Effects of galanin on passive avoidance response, elevated plus-maze learning,
      and spontaneous alternation performance in mice.
AB  - The present study was done to characterize the effects of intracerebroventricular
      injection of galanin (GAL) on memory processes by observing passive avoidance
      response, elevated plus-maze learning, and spontaneous alternation performance in
      mice. An intermediate dose (3 micrograms) of GAL (3 micrograms) significantly
      decreased step-down latency of passive avoidance response when given 15 min
      before training, whereas in particular the middle doses (0.3 and 1 microgram) of
      GAL significantly decreased it when given 15 min before retention tests. However,
      GAL (0.3-10 micrograms) was ineffective when given immediately after training.
      Physostigmine (0.2 mg/kg), a cholinesterase inhibitor, and oxotremorine (0.01 and
      0.03 mg/kg), a cholinergic agonist, significantly inhibited the shortening of
      step-down latency induced by GAL (0.3 microgram) administered 15 min before
      retention tests, indicating the involvement of cholinergic dysfunction in the GAL
      (0.3 microgram)-induced shortening of step-down latency. In contrast, GAL (0.3-3
      micrograms) failed to influence transfer latency in elevated plus-maze learning
      or percent alternation in spontaneous alternation performance. These results
      suggest that the activation of cholinergic neurons improves memory dysfunctions
      induced by GAL, which primarily impairs retrieval processes of memory. The lack
      of effects of GAL on the elevated plus-maze learning and spontaneous alternation
      performance may result from the selective effects of GAL in different learning
      paradigms.

PMID- 8545254
TI  - Characterization of murine PACAP mRNA.
AB  - A murine PACAP precursor cDNA was isolated by screening a brain cDNA library. The
      amino acid sequence of the precursor was highly similar (from 81% to 93%
      similarity) to its rat, human, and ovine counterparts. The primary structure of
      murine PACAP is identical with those from sheep, humans, and rats, indicating
      that the mature PACAP is well conserved among mammals. Northern blot analysis
      revealed that the approximately 2.4 kb transcript for the PACAP precursor is
      expressed in murine brain. The verification that murine PACAP is identical to its
      human counterpart provides a rationale for physiological and pathophysiological
      studies of PACAP in mice.

PMID- 8545253
TI  - All prepro-VIP-derived peptides, except PHI/PHV, are expressed in the female rat
      anterior pituitary and increased by estrogen.
AB  - The expression of VIP precursor products: prepro-VIP(22-79), peptide histidine
      isoleucine (PHI), peptide histidine valine (PHV), prepro-VIP(111-122), VIP,
      prepro-VIP(156-170), and prepro-VIP mRNA in the anterior pituitary of estrogen
      treated, ovariectomized rats, of ovariectomized controls, and of sham-operated
      controls was examined. Using radioimmunoassays based on antisera against each of
      the prepro-VIP sequences, we found that all sequences were expressed and markedly
      induced by estrogen, except PHI and PHV, which both were undetectable. By
      immunohistochemistry, it appeared that the number of cells immunoreactive for
      each of these sequences was increased in the estrogen-treated animals. However,
      PHI/PHV-immunoreactive cells could not be detected, despite the use of four
      different PHI antisera with different specificities. Estrogen treatment increased
      the prepro-VIP mRNA as judged by Northern blotting. In situ hybridization signals
      for both VIP mRNA and PHI mRNA were observed in few pituitary cells from control
      animals whereas strong positive signals were observed in a larger number of cells
      after estrogen treatment. The findings show that estrogen causes activation of
      the VIP gene expression in anterior pituitary cells, and that the absence of PHI
      and PHV probably is due to translational or posttranslational events.

PMID- 8545255
TI  - Radioimmunoassay for hexarelin, a peptidic growth hormone secretagogue, and its
      pharmacokinetic studies.
AB  - A radioimmunoassay (RIA) method for hexarelin, a peptidic growth hormone
      secretagogue, has been developed and applied to pharmacokinetic studies in dogs
      following an IV dose of 1 microgram/kg, and three SC doses of 1, 10, and 100
      micrograms/kg. The sensitivity of the assay was determined to be 1.34 fmol/assay.
      Cross-reactivity of the antiserum with nine hexarelin analogues was less than 1%
      upon modification of positions 3, 4, or 5 of the peptide. No apparent cross
      reaction with endogenous hexarelin metabolites were observed. Intra- and
      interassay coefficients of variation were less than 3% and 4%, respectively.
      Intravenous bolus pharmacokinetics of hexarelin displayed a high terminal half
      life of 120 min, a fractional plasma clearance of 4.28 ml/min/kg, and a volume of
      distribution at steady state of 387.7 ml/kg. Following SC administration of
      hexarelin, despite the increase in dose administered, both clearance (3.93-5.17
      ml/min/kg) and volume of distribution (316-544 ml/kg) parameters remained
      constant over the dose range studied.

PMID- 8545256
TI  - Bombesin-mediated calcium fluxes in myenteric plexus neurons.
AB  - Dual excitation microfluorimetry (Fura-2) was used to measure changes in
      intracellular calcium ([Ca2+]i) in individual cultured guinea pig myenteric
      neurons. Bombesin (5-500 nM) induced concentration-dependent increases in [Ca2+]i
      responses, with a maximal effect at 500 nM (56% of neurons responding, mean peak
      Ca2+ response 244 +/- 25 nM vs. basal 65 +/- 7 nM). Removal of Ca2+ from the
      median did not affect the initial [Ca2+]i peak but eliminated the subsequent
      plateau phase. The [Ca2+]i responses to bombesin was abolished by preincubation
      with thapsigargin (1 microM), a Ca(2+)-ATPase inhibitor (91 +/- 7% inhibition).
      [Ca2+]i responses to bombesin were inhibited by U73122 (1 microM), an inhibitor
      of phospholipase C (84 +/- 6% inhibition).

PMID- 8545257
TI  - The CCKB antagonist, L-365,260, attenuates fear-potentiated startle.
AB  - The neuropeptide cholecystokinin (CCK), via the CCKB receptor, increases
      behaviors associated with anxiety in laboratory animals and humans. The present
      experiment assessed the role of endogenous CCKB function in fear-potentiated
      startle, a test of "anxiety" in rats. The amplitude of the acoustic startle
      response is potentiated if preceded by a stimulus that has been previously paired
      with shock. Pretreatment with the CCKB antagonist L-365,260 (0, 0.1, 1.0, and
      10.0 mg/kg, IP) did not affect baseline acoustic startle amplitudes, but dose
      dependently decreased fear-potentiated startle. These results indicate that the
      specific attenuation of fear-potentiated startle induced by L-365,260 was not due
      to a general decrease in motor responsivity. The present findings are consistent
      with the effects of CCKB antagonists in other tests measuring anxiety in animals.

PMID- 8545258
TI  - NG-nitro-L-arginine methyl ester and alpha-methyl-L-ornithine inhibit kyotorphin
      synthetase from rat brain.
AB  - Kyotorphin (KTP), an antinociceptive dipeptide (Tyr-Arg), is formed by KTP
      synthetase from L-Tyr and L-Arg in the brain. We examined the effects of various
      L-Arg analogues on immunoreactive KTP (iKTP) formation by KTP synthetase purified
      partially from rat brain. The NO synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME), but not NG-nitro-L-arginine and N-iminoethyl-L-ornithine,
      suppressed iKTP formation by KTP synthetase from 1 mM of L-Arg and L-Tyr, the
      IC50 value being 2.33 mM. Similarly, alpha-methyl-L-ornithine (alpha-MO)
      inhibited KTP synthetase, the IC50 value being 2.51 mM. D-Arg at high
      concentrations also exhibited a weak inhibitory effect. Kinetic experiments
      indicated that the inhibition by L-NAME and alpha-MO of KTP synthetase is
      competitive. Thus, these L-Arg analogues appear to act as the competitive
      inhibitor of KTP synthetase.

PMID- 8545259
TI  - Somatostatin levels during infancy, pregnancy, and lactation: a review.
AB  - This paper reviews research on somatostatin (SS) levels during infancy,
      pregnancy, and lactation. Neonates have elevated levels of circulating SS, which
      reach a peak at the age of 3 months and then decrease gradually, but remain
      elevated during the first years of life. SS response to feeding is not well
      developed in newborns. Elevated levels are also found during pregnancy,
      especially during the late phases. Influence of sucking on maternal SS plasma
      levels is varied and could be related to vagal stimulation. pH levels, and basal
      SS levels. SS has been found in high concentrations in maternal milk. Milk-borne
      SS appears to be protected from proteolysis by milk components, but apparently SS
      is not absorbed in its intact form through the duodenal wall and its effects
      could be indirect. More research is needed to determine the regulating role of
      milk-borne SS and the contribution of SS to development.

PMID- 8545260
TI  - Cultural psychiatry. Theoretical, clinical, and research issues.
AB  - As a discipline, cultural psychiatry has matured considerably in recent years and
      the ongoing quality of its theoretical, clinical, and research development holds
      great promise. The contemporary emphasis on culture as process permits a deeper
      analysis of the complexities of sociosomatics--the translation of meanings and
      social relations into bodily experience--and, thus, of the social course of
      illness. We also are learning a great deal more about cultural processes that
      affect therapy, including ethnopharmacologic and culturally valid family
      interventions that are directly relevant to patient care and mental health
      policy. And an important set of studies is examining the trauma experienced by
      refugees and immigrants. But at the same time many disquieting findings still
      point to the limited impact of cultural psychiatry on knowledge creation and
      clinical application in psychiatry. The failure of the cultural validation of DSM
      IV is only the most dismaying. The persistent misdiagnosis of minority patients
      and the continued presence of racial bias in some treatment recommendations are
      also disheartening, as is the seeming contempt of many mainstream psychiatrists
      for culturally defined syndromes and folk healing systems. Widespread inattention
      to ethnic issues in medical ethics is another source of dismay. It is for these
      reasons that the culture of psychiatry itself becomes as important as the culture
      of patients as a topic for research and intervention. Most of the world still
      suffers from a terrible lack of basic mental health services, including life
      saving medications and hospital beds. In the face of these limitations, and
      because of the increasing multicultural and pluralistic reality of contemporary
      life, the growing interpretive bridges linking indigenous systems of illness
      classification and healing to Western nosologies and therapeutic modalities
      become even more essential and the reluctance of mainstream clinicians to explore
      folk healing methods more incomprehensible. Psychiatry needs new ways of
      delivering culturally appropriate care to the disenfranchised and the destitute,
      for whom mainstream approaches are often too expensive, foreign, and centralized.
      As a profession, we also have much to learn from indigenous diagnosticians and
      therapists. Finally, psychosomatic, mind-brain, behavioral health, and
      psychopathologic investigations need to configure the social world in their
      paradigms of research if we are to understand better the sources and consequences
      of mental illness. Psychiatry can no more afford to be contextless than it can
      afford to be mindless or brainless.

PMID- 8545261
TI  - Culture and psychiatric diagnosis. Impact on DSM-IV and ICD-10.
AB  - Psychiatric diagnosis is a clinical activity subjected to more clinical
      determinants than many others. Based on a unique human encounter, it resorts to a
      variety of informational sources and interpretive mechanisms that reflect strong
      cultural biases. Each diagnostic system has mirrored the period of history in
      which it became established. This article examines the effect of culture on the
      two best-known diagnostic and classificatory systems: the DSM-IV and the ICD-10
      Section V. It is important to minimize the ethnocentrism of disease categories in
      psychiatry and to highlight sources of possible cultural biases in the diagnostic
      interview and the diagnostic process in general, including assessment of
      comorbidity levels of stress, multiaxial impairment, everyday functioning, and
      management recommendations. Research on these issues and on diagnostic and
      measurement instruments must be pursued without sacrificing mainstream
      conventions.

PMID- 8545262
TI  - Cultural considerations in the assessment and treatment of religious and
      spiritual problems.
AB  - Scott Peck, a psychiatrist who has written several books on the spiritual
      dimensions of life, including the best-selling The Road Less Traveled, gave an
      invited address which drew a standing-room only audience at the 1992 Annual
      Meeting of the American Psychiatric Association. He pronounced that psychiatrists
      are "ill-equipped" to deal with either religious/spiritual pathology or health.
      Continuing to neglect religious/spiritual issues, he claimed, would perpetuate
      the predicaments that are related to psychiatry's traditional neglect of these
      issues: "occasional, devastating misdiagnosis; not infrequent mistreatment; an
      increasingly poor reputation; inadequate research and theory; and a limitation of
      psychiatrists' own personal development." In recent years, there have been a
      number of developments that have begun to redress psychiatry's cultural
      insensitivity to the religious and spiritual dimensions of life. In 1990, the APA
      Committee on Religion and Psychiatry initiated an APA Position Statement entitled
      "Guidelines Regarding Possible Conflict Between Psychiatrists' Religious
      Commitments and Psychiatric Practice." These guidelines emphasized that
      "psychiatrists should maintain respect for their patient's beliefs ... and not
      impose their own religious, antireligious, or ideologic systems of beliefs on
      their patients, nor should they substitute such beliefs or ritual for accepted
      diagnostic concepts or therapeutic practice." These guidelines reinforce the
      importance of acknowledging and respecting differences in religious/spiritual
      beliefs between clinicians and their patients. More recently, the Accreditation
      Council for Graduate Medical Education published the new "Special Requirements
      for Residency Training in Psychiatry," which incorporated several changes
      mandating instruction about gender, ethnicity, sexual orientation, and
      religious/spiritual beliefs. Finally, the inclusion of "religious or spiritual
      problem" as a diagnostic category for the first time in the DSM-IV acknowledges
      that religious and spiritual issues can be the focus of psychiatric consultation
      and treatment. John McIntyre, MD, former APA President, and Harold Pincus,
      Director of the APA's Office of Research, observed that this new entry in DSM-IV
      was "a sign of the profession's growing sensitivity not only to religion but to
      cultural diversity generally." It is hoped that these developments will increase
      the accuracy of diagnostic assessments, reduce iatrogenic harm from misdiagnosis,
      and increase the mental health professional's respect for individual beliefs and
      values.

PMID- 8545263
TI  - Culture and major depression. Current challenges in the diagnosis of mood
      disorders.
AB  - Although the religious and spiritual dimensions of life are among the most
      important cultural factors structuring human experience, behavior, and illness
      patterns, mainstream psychiatry has tended either to ignore or pathologize the
      religious and spiritual issues that clients bring into treatment. To redress this
      lack of sensitivity, the authors of this article propose a new diagnostic
      category to the DSM-IV Task Force entitled "Religious or Spiritual Problem"
      (V62.61). It is hoped that the acceptance of this category will increase the
      accuracy of diagnostic assessments, reduce iatrogenic harm from misdiagnosis, and
      increase mental health professionals' respect for individual beliefs and values.

PMID- 8545264
TI  - The cultural context of anxiety disorders.
AB  - About a century ago, George Crile, a surgeon and experimental physiologist,
      suggested that the meaning of pain could be discovered in the context of
      evolution. Pain is a signal of a physical injury that would be otherwise ignored
      by the individual, a form of ignorance that would ultimately have mortal
      consequences. Crile believed that pain has a second purpose, that has important
      implications for how psychiatry now understands the emotions, specifically fear
      and anxiety. In essence, he suggested that fear is the memory of pain, and its
      adaptive advantage is that it enables individuals to anticipate and avoid injury.
      Fear-as-memory could be acquired either through individual experience (learned
      fear) or through species experience (instinctive fear). Among other things, this
      conception of pain and fear explained why surgical shock (from physical injury)
      and nervous shock (induced by fear or fright) appeared, at times, to provoke a
      similar physiologic response--a phenomenon first commented on by the British
      surgeon, Herbert Page. With this simple grammar, injury-pain-fear, Page and Crile
      laid the foundations for the modern concept of psychogenic trauma, extending the
      old idea of "trauma," meaning a wound or physical injury, to include
      psychological experiences and processes. The modern conception was completed by
      Freud, by connecting one more emotional state, anxiety. If fear is not simply a
      memory of pain but a memory that is bound to stimuli in the here-and-now, then
      anxiety is memory set loose. Put in other words, anxiety is the capacity to
      imagine pain and not merely to recollect pain. From the time of Beyond the
      Pleasure Principle (1919), anxiety took on a life of its own, so to speak, no
      longer part of the constellation of emotions and experiences identified by Page
      and Crile. Without an external object toward which to direct itself, fear becomes
      anxiety--a state of nervous anticipation of the unknown, of what is hidden in the
      shadows or penumbra of awareness. Anxiety is not a vector directed toward a
      threatening object or event in the environment but is situated in the person's
      own bodily experience, the workings of the mind, the Cartesian theater of self
      representation. As an experience and event located entirely within the psyche, to
      be mastered by asserting a strong ego, reflections on anxiety became one of the
      self-constituting experiences of the Western concept of the person. In
      contemporary psychiatry, the constellation of injury, pain, fear, anxiety,
      memory, and imagination would seem to live on mainly in the context of
      traumatogenic anxiety and PTSD.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8545265
TI  - Culture-bound syndromes.
AB  - Since its inception, scholars have struggled with the concept of CBSs. This
      struggle is reflected in the continuing use of a term that is confusing and
      inaccurate. Most authors would agree that the term "culture-bound syndrome" was
      intended to describe forms of otherwise common mental illness that are rendered
      unusual because of the pathoplastic influence of culture. It was intended not
      only to describe specific syndromes, but also meanings of illness and non-Western
      notions of disease causation. The term has become an anachronism, for the word,
      "syndrome," implies specific disease entities, not illnesses of attribution of
      idioms of distress. Furthermore, the word "bound" implies that the entities
      described are restricted to a single culture. Close examination reveals that many
      of the so-called "culture-bound" syndromes are found in multiple cultures that
      have in common only that they are "non-Western." It may be unreasonable to expect
      one term to describe these different concepts. The most accurate of the
      designations offered might be "folk diagnostic categories." Perhaps the most
      difficult question remaining is "How can we understand (and classify) these
      phenomena in such a way that highlights their uniqueness but does not dismiss
      them as too rare and exotic to warrant attention?" The first step is to recognize
      that the CBSs are a heterogeneous group of conditions. We must next acknowledge
      that the concepts represented may be difficult for the average Western clinician
      to recognize but, in their respective cultures, are neither rare nor unusual.
      With 80% of our increasingly shrinking world coming from "non-Western" cultures,
      a familiarity with non-Western notions of disease causation is particularly
      important for modern clinicians. Many authors have recommended that those CBSs
      that are "true" syndromes be classified together with their Western counterparts.
      In order to do this, the folk labels need to be put aside and the fundamental
      components of each disorder examined. Each entity would have to be placed in the
      body of the classificatory manual, and defined by its symptoms, not by the fact
      that its form is highly influenced by culture.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8545266
TI  - Eating disorders and disordered eating in different cultures.
AB  - Clinical experience and research have moved the field toward greater recognition
      and differentiation of eating disorders as independent categories of mental
      disorder. Shorter's historical analysis, however, suggests that it may be useful
      to reconsider the relationship of AN and BN to the broader class of somatoform
      disorders. Also, by conferring legitimacy on this socially and culturally
      constructed disorder, mental health professionals may have seriously
      underestimated their unanticipated influence in propagating eating disorders with
      publicity aimed at preventing and curing them. Inasmuch as it offers an
      alternative or complement to the prevailing cultural hypothesis, which focuses on
      the effect of Western esthetics rather than the sociology of health care
      institutions, and has important implications for policy and publicity about
      eating disorders, the question of how culture and Westernization affect the
      epidemiology and experience of eating disorders also requires further study.

PMID- 8545267
TI  - Transcultural aspects of dissociative and somatoform disorders.
AB  - A brief review of the cross-cultural literature on dissociative and somatoform
      disorders with emphasis on US Hispanic populations has been provided. A brief
      description of the psychopathology of somatizing syndromes has been given as have
      some critiques of current nosologic systems. Cultural influences that may color
      the expression of somatic manifestations have been outlined. Although it is often
      difficult to disentangle the contribution of ethnicity from other demographic
      factors, and although there are plenty of methodologic shortcomings, most studies
      reinforce the view that culture exerts a powerful influence in shaping symptom
      presentation and determining health-related attitudes. Future work using
      instruments such as the Composite International Diagnostic Interview (CIDI)
      (Rubio-Stipec M: The somatization schedule of the Composite International
      Diagnostic Interview: The use of the probe in 17 different countries; unpublished
      manuscript) that include a more culturally congruent list of somatizing symptoms
      may shed new light on the international distribution and mechanisms at play in
      these symptom presentations.

PMID- 8545268
TI  - Sociocultural and therapeutic perspectives on violence.
AB  - Violence is a complex behavior and like all behaviors it occurs in the context of
      culture. The causes of violence and the various ways that it becomes manifest are
      influenced by the prevailing attitudes of a society and that society's
      perspective on the aims and legitimacy of particular forms of violence. Violence
      encompasses a wide range of human behavior that has interacting biologic,
      psychological, and social components. This article has addressed the various
      theories of aggression and violence, diagnostic issues related to victimization
      by violence, and therapeutic concerns in treating both victims and perpetrators
      of violence.

PMID- 8545269
TI  - Cultural aspects of substance abuse and alcoholism. Assessment and management.
AB  - Cultures and ethnic groups within cultures prescribe, proscribe, or tolerate use
      of various psychoactive substances for social or personal purposes. In the United
      States, these ethnic strictures and practices vary widely. Ethnic enculturation
      into particular psychoactive substances can either reduce the risk of substance
      abuse or greatly increase this risk. To function effectively in a multiethnic
      society, psychiatric physicians of North America should learn to assess the
      cultural and ethnic dimensions and effects of substance abuse among their
      patients. In addition, they should be culturally sensitive to those aspects of
      treatment that can impede or augment successful outcomes. Finally, any and all
      attempts at primary prevention, early recognition and intervention, and
      rehabilitation should reflect the complex cultural, political, economic, and
      religious factors that influence substance use and abuse.

PMID- 8545270
TI  - Ethnicity and psychotherapy. A component in the treatment of cocaine addiction in
      African Americans.
AB  - With a focus on the use of psychotherapy as a component in the comprehensive
      treatment of African Americans addicted to cocaine, this article reviews the
      literature on ethnicity and psychotherapy and discusses the main problems
      relevant to the planning of mental health and substance abuse services to
      minority populations in the United States. Some of the more salient areas are the
      relationship of cultural factors and substance abuse, the culturally determined
      possibilities and constraints in the treatment of substance abuse, the
      establishment of a culturally responsive psychotherapeutic approach that takes
      into account notions such as ethnic consciousness and self-esteem, and the
      therapist's effects on the proximal treatment situation. Research issues also are
      discussed, among them therapist-matching strategies, therapist's clinical skills,
      culturally responsive adaptations of psychotherapeutic frames and processes, and
      their effect on outcome.

PMID- 8545271
TI  - A cultural perspective on family theory and therapy.
AB  - Although family therapists' conceptualizations of culture include ethnicity,
      nationality, religion, generation, gender, class, and sexual orientation, this
      article focused on ethnicity and families in the United States. A review of the
      literature reveals that effective family therapy is both sensitive to the
      family's cultural heritage and attuned to the unique interactional patterns,
      attitudes, feelings, and behaviors of each family with whom the therapist works.
      Culturally sensitive family therapy attempts to transcend cultural barriers,
      while respecting the cultural identity and integrity of the individual family
      members, the family unit as a whole, and the therapist. As multiculturalism has
      become increasingly emphasized in the United States, family therapists are
      challenged to facilitate families' efforts to reconnect with their cultural
      heritage to preserve a sense of belonging and identity, while simultaneously
      helping them adapt to their evolving cultural context.

PMID- 8545272
TI  - Ethnicity and psychopharmacology. Bridging the gap.
AB  - Taken together, the literature reviewed clearly indicates that the disposition
      and effect of a large number of psychotropic agents are influenced substantially
      by ethnicity and culture. Recent advances in the realm of pharmacokinetics,
      pharmacogenetics, and pharmacodynamics have led to a greater understanding of
      some of the mechanisms responsible for such differences. In comparison, much less
      currently is known regarding how various psychosocial factors impinge on drug
      responses in different cultural settings. Progress in research in this area is
      important for clinical reasons, as psychiatric clinicians will increasingly be
      confronted with patients with divergent ethnic and cultural backgrounds. In
      addition, knowledge derived from such research will contribute significantly to a
      better understanding of how the effects of psychotropic agents are mediated, and
      also should be valuable for the drug development industry that will have to take
      into account the increasingly diversifying domestic and international markets.

PMID- 8545273
TI  - Cultural formulation and comprehensive diagnosis. Clinical and research
      perspectives.
AB  - The Cultural Formulation constitutes a distillation of the new cross-cultural
      psychiatry, designed by the NIMH Culture and Diagnosis Group, and incorporated
      into DSM-IV as one of its significant innovations. The role of the Cultural
      Formulation in clinical care, training, and research can be better understood and
      its impact extended when considered within the framework of a comprehensive
      diagnostic model.

PMID- 8545274
TI  - The economics of pain. Mental health care costs among minorities.
AB  - In this article, we have underlined the importance of providing high-quality
      health and mental health services to the ethnic minority populations of the
      United States. We also have highlighted the complexities associated with the
      provision of these services, with special attention to the factors affecting
      health insurance coverage and the patients' socioeconomic conditions. Finally, we
      have advanced some potential solutions to the current health care crisis,
      particularly as they relate to minorities. In reviewing these solutions, we have
      focused primarily on the role of the service providers, third-party payors,
      poverty, and cultural and language barriers.

PMID- 8545275
TI  - Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor
      cell line, and EGF immunoreactive proteins are present at sites of metastasis in
      the stroma of lymph nodes and medullary bone.
AB  - Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at
      a frequency in excess of that which would be predicted by random tumor cell
      dissemination. In order to determine whether chemoattractants in these organs
      promote organ-specific metastasis, we utilized human cell lines derived from
      and/or related to these organs as sources of potential chemoattractants.
      Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1
      (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1
      prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition,
      secretory proteins from a human prostatic stromal cell line (hPS) and from the
      TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of
      the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites
      represent organs of hematopoietic/lymphoid proliferation and activation, we
      undertook identification of specific cytokines present at these sites which may
      promote the chemomigration of prostate tumor cells. In this context, the
      cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis
      factor-beta, transforming growth factor-beta, interferon alpha 2-a, and
      granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration
      of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal
      growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells
      through the Boyden chambers in a dose-dependent manner. Western blot analysis of
      secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1
      identified EGF-immunoreactive proteins in all cases. In addition, EGF
      immunoreactivity was localized to the stroma of the human prostate, the
      osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and
      trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the
      cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line,
      and that EGF within the stroma of pelvic lymph nodes and medullary bone may act
      as a chemoattractant for prostate tumor cells, thereby facilitating the
      preferential formation of metastatic foci within these organs.

PMID- 8545276
TI  - Dual monoclonal antibody immunoassay for free prostate-specific antigen.
AB  - Prostate-specific antigen (PSA) is the most important tumor marker for early
      detection and monitoring of prostate cancer (PCa) patients. PSA is also elevated
      in many patients with benign prostatic hyperplasia (BPH). The study of the serum
      PSA forms, free PSA (f-PSA) and PSA complexed with alpha 1-antichymotrypsin (PSA
      ACT), may improve the discrimination between PCa and BPH. An immunoassay specific
      for f-PSA is reported with very low cross-reactivity (0.7%) to PSA-ACT. Serum
      specimens from BPH and PCa patients (determined by biopsy) with PSA levels from <
      1 to > 100 ng/ml were tested. No f-PSA was detected in serum specimens from
      normal females (N = 50). Low levels (0-0.3 ng/ml) were detected in specimens from
      healthy males (N = 60). In specimens from PCa and BPH patients, the f-PSA to
      total PSA ratio (f/t) was found to range from 1% to higher than 60%. While
      maintaining an 80% sensitivity for cancer, the f/t ratio improved specificity to
      approximately 80%, as compared to 55% for total PSA alone. The receiver operating
      characteristics (ROC) curve analysis of the f/t ratio displayed a greater area
      under the plot (0.84) compared to total PSA alone (0.745). The results
      demonstrate that the f/t ratio significantly increases specificity for PCa
      detection compared to total PSA alone, showing the potential clinical value of
      the f-PSA immunoassay.

PMID- 8545277
TI  - Roles of estrogen and SHBG in prostate physiology.
AB  - Heretofore, the function of estrogen in the prostate, other than as an
      antiandrogen, has been unclear. In this review of a growing fund of knowledge
      about both estrogen and the plasma protein, sex hormone-binding globulin (SHBG),
      or testosterone-estradiol binding globulin (TeBG), the hypothesis is proposed
      that estrogen, mediated by SHBG, participates with androgen in setting the pace
      of prostatic growth and function. It is suggested that the estrogen not only
      directs stromal proliferation and secretion, but also, through IGF-I, conditions
      the response of the epithelium to androgen.

PMID- 8545278
TI  - Anatomy and innervation of the rhabdosphincter of the male urethra.
AB  - The striated sphincter of the male urethra and its innervation are still a
      subject of controversy. Essentially, two concepts of its anatomy can be found in
      the literature. Some authors describe the rhabdosphincter as part of the
      urogenital diaphragm caudal to the prostate, others as a striated muscle which
      extends from the base of the bladder to the "urogenital diaphragm." In a combined
      anatomic-histologic study the striated sphincter and the pudendal nerve were
      examined by means of anatomical dissections and serial anatomical as well as
      histological sections of 12 male pelves. Furthermore, radical prostatectomy was
      performed in a cadaver specimen; subsequently, the so-called "urogenital
      diaphragm" was excised and then examined histologically. The varying number of
      striated muscle fibers caudal to the prostate is of particular interest. In
      fetuses, there are abundant striated muscle fibers dorsal to the membranous
      urethra, where they are arranged as a circular collar around the urethra. In the
      adult male, hardly any striated muscle fibers can be found dorsal to the urethra;
      in a majority of cases this region is devoid of striated muscle fibers. Inserting
      dorsally in the perineal body, the fibers form an omega-shaped loop around the
      anterior and lateral aspects of the membranous urethra. The existence of a
      "urogenital diaphragm" and a strong, circular, striated "external sphincter
      urethrae" completely encircling the urethra caudal to the apex of the prostate
      could not be confirmed by our anatomical and histological investigations. Our
      study shows that the striated muscle fibers run in a cranial direction from the
      bulb of the penis to the base of the bladder along the anterior and lateral
      aspects of the prostate and the membranous urethra. Further dissection studies
      revealed that the rhabdosphincter is supplied by branches of the pudendal nerve
      after leaving the pudendal canal.

PMID- 8545279
TI  - Intravenous vs. intraprostatic administration of N-methyl-N-nitrosourea to induce
      prostate cancer in rats.
AB  - To develop an improved model of human prostate cancer, 16-wk-old Wistar rats were
      treated orally for 18 days with the antiandrogen, flutamide (50 mg/kg body weight
      [BW]/day), followed by 3 days of s.c. testosterone (100 mg/kg BW). There were the
      only treatments the control animals received (Group 1, n = 10). On the day after
      the third testosterone injection, N-methyl-N-nitorsourea (MNU) was administered
      via the tail vein at a dose of 50 mg/kg BW (Groups 2, n = 40 and 3, n = 20); in
      some rats, a second dose was delivered by the same route 22 wk later (Group 3). A
      smaller dose of MNU (15 mg/kg BW) was administered intraprostatically (Group 4, n
      = 20) to a fourth group. In Groups 2, 3, and 4, silastic capsules containing
      testosterone were implanted s.c. approximately every 6 wk beginning 1 wk post
      MNU. Accessory sex gland tumors arose in MNU-treated rats in Group 2 (12/40,
      30%). Group 3 (8/20, 40%), and Group 4 (8/20, 40%); 90% were macroscopic (25/28).
      There were no neoplasms in these organs in the control rats (Group 1, 0/10).
      These accessory sex gland neoplasms were adenocarcinomas or undifferentiated
      carcinomas which appeared to be derived from the prostate based on location and
      histological characteristics, although the size and spread of some of the tumors
      precluded definitive localization of the tissue of origin. The incidence of these
      neoplasms was similar in rats given a single dose of MNU intraprostatically or
      two doses of MNU i.v., but the animals treated intraprostatically maintained
      higher body weights and developed fewer extraneous tumors. The average (+/- SD)
      latent period for clinical or postmortem detection of prostate neoplasia after
      MNU was shortest in the rats given two i.v. doses (39 +/- 3 wk) compared with the
      single i.v. dose (45 +/- 6 wk) or an intraprostatic dose (56 +/- 7 wk). In 57% of
      the cases (16/28), the prostate tumors metastasized to distant sites. An
      activating point mutation was detected in codon 12 of the Ki-ras oncogene in the
      MNU-induced primary prostate tumors (8/10 examined), and metastases arising from
      these prostate tumors (2/3) but was absent in normal prostate tissue (0/6). This
      study demonstrates that two systemic doses of MNU increase the incidence and
      decrease the latency of prostate neoplasms compared with a single dose, and that
      a single dose of MNU injected intraprostatically induces prostate adenocarcinoma
      without many of the other tumors and weight loss typically found after i.v.
      administration.

PMID- 8545280
TI  - Point mutations in the Ki-ras2 gene of codon 12 in the Dunning R-3327 Prostatic
      Adenocarcinoma system.
AB  - Detection of point mutations in the Dunning System with the Ki-ras2 gene in the
      first and second positions of codon 12 exon I, has been performed using allele
      specific oligonucleotide (ASO) primers. PCR generated 94bp templates and genomic
      DNA extracted from the Dunning cell lines AT-1, AT-3, Mat-Lu, and Mat-Lylu were
      tested. Our investigation revealed that the first and second positions of codon
      12 have undergone either transitions or transversions from the wild type sequence
      (GG). Dorsal prostate (DP) solid tissues used as controls revealed the wild type
      configuration as well as transversions at both positions, in addition to a
      transition in the first position for Mat-Lu. The most aberrant of the Dunning
      lines (AT-3 and Mat-LyLu) collectively displayed sequence changes (transitions
      and transversions) with no evidence of the wild type configuration. These
      findings are supportive of biometric studies (area, shape factor, and motility)
      along with adhesion and invasion assays done in our laboratory in correlating
      genotypic and phenotypic properties to metastatic potential.

PMID- 8545281
TI  - Evaluation of adjuvant estramustine phosphate, cyclophosphamide, and observation
      only for node-positive patients following radical prostatectomy and definitive
      irradiation. Investigators of the National Prostate Cancer Project.
AB  - In 1978 the National Prostate Cancer Project launched two protocols evaluating
      adjuvant therapy following surgery (Protocol 900) or irradiation (Protocol 1,000)
      for clinically localized prostate cancer. All patients underwent staging pelvic
      lymphadenectomy. Following definitive treatment, patients were randomized to
      either cyclophosphamide 1 gram/m2-IV every 3 weeks for 2 years, estramustine
      phosphate 600 mg/m2-po daily for up to 2 years, or to observation only. Patient
      accession closed in 1985 and includes 184 to Protocol 900 (170 evaluable) and 253
      to Protocol 1,000 (233 evaluable). Lymph node involvement was identified in 198
      patients (49% of total), 29% in Protocol 900, 63% in Protocol 1,000. Median
      progression-free survival (PFS) for patients with nodal involvement in Protocol
      1,000 receiving estramustine phosphate adjuvant was longer (37.3 mo) compared to
      cyclophosphamide (30.9 mo) and to no treatment (20.9 mo). Median PFS for patients
      with limited nodal disease in Protocol 1,000 was longer (39.9 mo), regardless of
      adjuvant, compared to extensive nodal disease (20.7 mo). However for patients
      with extensive nodal involvement, those receiving adjuvant estramustine phosphate
      experienced a significantly longer median PFS (32.8 mo) compared to adjuvant
      cyclophosphamide (22.7 mo) and no adjuvant (12.9 mo). We conclude that adjuvant
      estramustine phosphate is of benefit in prostate cancer patients with extensive
      pelvic node involvement receiving irradiation as definitive treatment.

PMID- 8545282
TI  - Ductal heterogeneity in rat dorsal-lateral prostate.
AB  - Given the lobar complexity of the rat prostate at the morphological level,
      differences in secretory protein expression were investigated in individual
      prostatic ducts that constitute the subdivisions of the dorsal-lateral prostate,
      ie., the dorsal prostate, lateral prostate type 1 and lateral prostate type 2.
      For this purpose, individual prostatic ducts were microdissected from these
      prostatic lobes, photographed, and secretions subsequently collected from
      individual prostatic ducts and analyzed by Western blot for the expression of DP
      1 and probasin, two major proteins expressed in rat the dorsal-lateral prostate.
      Many individual glands constituting the dorsal prostate, lateral prostate type 1
      and lateral prostate type 2 co-express DP-1 and probasin, but at vastly different
      levels. DP-1 is a major secretory protein of the dorsal prostate and lateral
      prostate type 1, while probasin is the major secretory protein of the lateral
      prostate type 2. A small percentage of individual ducts of the dorsal prostate,
      lateral prostate type 1 and lateral prostate type 2 express either DP-1 or
      probasin. However, most of the individual prostatic ducts constituting the dorsal
      prostate and lateral prostate type 1 express DP-1 at high levels and probasin at
      low levels. Conversely, most of the individual prostatic glands that constitute
      the lateral prostate type 2 express probasin at high levels and DP-1 at low
      levels. This study emphasizes the morphological and functional heterogeneity
      within the prostate gland.

PMID- 8545283
TI  - Presentation of prostate tumor antigens by dendritic cells stimulates T-cell
      proliferation and cytotoxicity.
AB  - Dendritic cells (DCs) are "professional" antigen-presenting cells capable of
      stimulating T-cell proliferation and cytotoxicity when loaded with and presenting
      specific antigens, including tumor antigens. We demonstrated the stimulation of
      an autologous cytotoxic T-cell response elicited by DC loaded with autologous
      tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen
      is prostate-specific membrane antigen (PSMA), which is overexpressed in prostate
      cancer patients. We identified a HLA-A2 motif in PSMA, isolated patient DC,
      loaded peptide into DC, and stimulated autologous T cells to proliferate. The
      ability to use DC for presentation of either tumor or peptide antigen in an HLA
      restricted fashion in order to stimulate T-cell proliferation and cytotoxicity
      demonstrates the potential of this technology for development of a prostate
      cancer vaccine.

PMID- 8545284
TI  - Management of transient ischaemic attacks and stroke.
AB  - The management of stroke and transient ischaemic attacks (TIAs) has changed
      greatly in the last two decades. The importance of good blood pressure control is
      the hallmark of stroke prevention. Large multicentre trials have proven beyond
      doubt the value of aspirin in TIAs, warfarin in patients with atrial fibrillation
      and embolic cerebrovascular symptoms, and carotid endarterectomy in patients with
      carotid TIAs. There seems little doubt that patients managed in acute stroke
      units are more likely to be independent at six months than those managed in a
      general medical ward. This article emphasizes the importance of basing clinical
      management on simple history taking and examination and appropriate
      investigation. This, combined with knowledge of the natural history risk of TIA
      and stroke and the results of randomised trials, allows individuals to be managed
      in the most appropriate manner. This review is designed to be a practical guide,
      useful in the day to day management of patients with cerebrovascular disease.

PMID- 8545285
TI  - Discussing cardiopulmonary resuscitation with patients and relatives.
AB  - This paper aims to give clear guidance for doctors working in the UK about their
      responsibilities when discussing cardiopulmonary resuscitation with patients and
      their relatives. The ethical and legal framework for making decisions is outlined
      and the commonly encountered dilemmas are discussed.

PMID- 8545286
TI  - The prevalence of drivers in acute geriatric wards.
AB  - An audit of 150 patients on five acute geriatric wards found that 28 (19%) still
      drove. Forty-three (28%) used to drive but had given up, whilst 79 (53%) (76 of
      whom were female) had never driven. Former drivers gave the main reason for
      stopping as cost. No driver could recall being advised about driving by a doctor.
      Twenty-two drivers (79%) had a significant clinical condition that could affect
      driving, ranging from blackouts to arthritis. It is recommended that all elderly
      patients should be asked if they drive and any clinical conditions they might
      have that would adversely affect their driving be sought. Appropriate advice
      should be given by doctors to their elderly patients in order to safeguard them
      and the public from road traffic accidents.

PMID- 8545287
TI  - The development of healthcare services for drug misusers and prostitutes.
AB  - With the advent of human immunodeficiency virus (HIV) and the increase of drug
      misuse in the UK, the Government wishes primary care to play a greater part in
      treating drug problems in the hope of preventing the spread of HIV. Drug misusers
      do not avail themselves of traditional services and many are not registered with
      general practitioners. In response to this Liverpool Health Authority and Family
      Health Service Authority commenced a new salaried post to provide primary care
      services to special groups such as injecting drug misusers and prostitutes.
      Judgemental attitudes towards drug misusers, their high mobility and being a
      transient population play a part in the reasons why drug misusers find it
      difficult to access primary healthcare. Drug misusers have high morbidity related
      to their drug misuse. Many of these conditions, if treated early, can prevent the
      need for more intensive intervention. Although drug misusers may present with a
      condition requiring immediate treatment, the opportunity is used to provide other
      healthcare such as hepatitis B vaccinations, sexually transmitted infection
      screening, contraception and HIV/hepatitis B testing. The sero prevalence of anti
      HBc in injecting drug misusers is 45.5%. Due to their high morbidity and
      associated costs, the requirements of these groups may conflict with the
      objectives of budget-holding practices. If general practitioners are unable to
      respond to their problems, then health care providers and purchasers will have to
      consider similar schemes in areas which have a higher prevalence of drug misuse
      in order to provide appropriate healthcare for these vulnerable groups.

PMID- 8545288
TI  - The management of central post-stroke pain.
AB  - Central post-stroke pain (CPSP) used to be known as 'thalamic syndrome'. Early
      post-mortem studies showed that many cases had extrathalamic lesions, and modern
      imaging methods have confirmed and extended these findings. CPSP affects between
      2 and 6% of stroke patients, ie, there is an annual incidence in the UK of
      between 2000 and 6000. Most patients with CPSP appear to be younger than the
      general stroke population, and usually to have relatively mild motor affliction;
      thus they may live for many years, giving a prevalence perhaps as high as 20,000.
      True CPSP, characterised by a partial or total deficit for thermal and/or
      sharpness sensations, is best treated initially with adrenergically active
      antidepressants. If these do not work, mexiletine may be added in suitable cases.
      Recent studies suggest that stimulation of the motor cortex or spinal cord by
      implanted electrodes may help patients resistant to medical treatment. Positive
      relaxation, as an adjuvant therapy, should be used in nearly all cases.
      Considerable or even total relief can be achieved in almost two thirds of
      patients. There is evidence that the sooner antidepressant treatment is begun,
      the more likely the patient is to respond; time should not be wasted trying
      conventional analgesics, which rarely have any significant effect.

PMID- 8545289
TI  - An audit of ANCA in routine clinical practice.
AB  - We have reviewed the medical records of 301/327 consecutive patients in whom anti
      neutrophil cytoplasmic antibodies (ANCA) were detected by the Regional Immunology
      Laboratory in Northern Ireland between January 1988 and October 1991 (45 months).
      We have collected data for each patient regarding age, sex, smoking habit, area
      of residence, and details of any other autoantibody activity. Clinical diagnosis
      was established, with the number of organ systems involved and the evidence for
      that involvement (symptomatic, biochemical, radiological, and histological).
      Diagnoses were divided into four groups according to their recognised vasculitic
      features and these were related to the pattern of immunofluorescence and maximum
      ANCA titre detected. The most frequent diagnosis was rheumatoid arthritis (18.2%
      of patients) and the connective tissue disorders as a whole accounted for 27.9%
      of patients. ANCA were also detected in a wide range of clinical conditions which
      are not associated with vasculitis and these patients were an important source of
      'false-positives'. The positive predictive value (PPV) of ANCA of all patterns
      and titres for vasculitic conditions was 27%, however, the detection of a
      classical ANCA pattern at high titre (> or = 1:640) was associated with an
      increased PPV of 75%. The coexistence of an antinuclear antibody (ANA) reduces
      the PPV of both classical and perinuclear ANCA, although perinuclear ANCA with
      antimyeloperoxidase specificity had an improved PPV. We conclude that ANCA
      testing should not be used as the only screening investigation for vasculitis but
      should be included in a rational investigative scheme. The interpretation of a
      positive ANCA result must take into account the presence of other autoantibodies
      and the full range of non-vasculitic conditions when the clinical situation is
      not typical of vasculitis.

PMID- 8545290
TI  - The effect of nilvadipine on bloodflow in the dorsal pedis artery in type 2
      diabetic patients--a study using duplex Doppler ultrasonography.
AB  - The effects of nilvadipine on the peripheral circulation in the lower extremities
      using a duplex system of two-dimensional colour and pulse Doppler ultrasonography
      were studied in 32 patients with type 2 diabetes mellitus and mild essential
      hypertension. The patients (19 men and 13 women) were randomly divided into
      treatment and control groups. The anatomical cross-sectional area and blood flow
      index of the dorsal pedis artery were determined by colour and pulse Doppler
      ultrasonography before and 60 min after administration of 4 mg nilvadipine or
      placebo. Pulse rate and blood pressure were measured simultaneously. There were
      no significant changes in pulse rate or blood pressure after administration of
      either drug. Both cross-sectional areas (from 4.3 +/- 0.4 to 5.2 +/- 0.5 mm2, p <
      0.05) and blood flow index (from 40.3 +/- 4.3 to 58.8 +/- 9.0, p < 0.05) were
      significantly increased in the treatment group, whereas there were no significant
      changes in either measurement in the control group. The findings showed that a
      single administration of nilvadipine increases blood flow in the dorsal pedis
      arteries of diabetic patients.

PMID- 8545292
TI  - Endoscopic balloon dilatation of duodenal strictures in Crohn's disease.
AB  - Endoscopic balloon dilatation of oesophageal and colonic strictures is now widely
      performed. Duodenal strictures due to Crohn's disease represent a difficult
      clinical problem as surgical intervention is a major undertaking and recurrences
      are common. We describe endoscopic balloon dilatation in three patients with
      obstructive symptoms from duodenal strictures due to Crohn's disease. The
      procedure appeared safe, was well tolerated and resulted in an excellent
      symptomatic response. This method is particularly suitable for short duodenal
      strictures and avoids the need for surgical intervention in this difficult group
      of patients.

PMID- 8545291
TI  - Soluble interleukin-2 receptor in patients with glomerular diseases.
AB  - In this study, we measured the soluble interleukin-2 receptor (sIL-2R) level to
      evaluate the cellular immune status in 61 patients with different types of
      glomerular diseases; 40 healthy volunteers were used as control. All patients
      with glomerular diseases had levels of serum sIL-2R significantly higher than
      those of the controls (766 +/- 59 vs 280 +/- 23 U/ml; p < 0.05). Even patients
      with normal renal function still had higher serum sIL-2R levels than the
      controls, no matter to which subgroups they belonged (primary glomerulonephritis,
      lupus nephritis or diabetic nephropathy). Serum sIL-2R levels were similar among
      the three subgroups. The serum levels of sIL-2R correlated well with age and were
      significantly higher in older patients, although this was not observed in the
      control group. Serum sIL-2R levels were significantly higher in patients with
      active urinary sediment and in patients with impaired renal function and showed a
      significant negative correlation with creatinine clearance (r = -0.56; p < 0.05).
      Although urinary and serum sIL-2R levels were quite well correlated, (r = 0.35; p
      < 0.05), the urinary levels of sIL-2R did not differ in patients with different
      disease activity or different renal functions although they had a significant
      correlation with 24-hour urinary protein (r = 0.39; p < 0.05). Patients with
      nephrotic syndrome also had higher urinary sIL-2R levels than other patients (529
      +/- 106 vs 280 +/- 31 U/ml; p < 0.05). We conclude that greater T-cell activation
      might contribute to the pathogenesis of different glomerulonephritis entities,
      and serum levels of sIL-2R can serve as a useful clinical marker of
      glomerulonephritis activity. Renal function influenced the serum levels of sIL-2R
      significantly. This factor must be considered when we interpret the data. Urinary
      sIL-2R levels did not reflect the disease activity as well. This might be due to
      the secondary influence of the extent of the glomerular protein leak. Further
      investigation is needed to define the exact excretory pathway of this substance.

PMID- 8545293
TI  - Successful pregnancy following aplastic anaemia.
AB  - Pregnancy following idiopathic aplastic anaemia is rare and is difficult to
      manage because of life-threatening episodes of bleeding and infections. Only a
      handful of cases has been reported in the literature. The pregnancies were
      unsuccessful in the majority. The present report describes a patient with
      moderately severe idiopathic aplastic anaemia who was managed with intensive
      haematological support leading to delivery of a healthy infant by caesarean
      section. Despite platelet transfusion refractoriness as a result of transfusions
      prior to pregnancy, adequate platelet transfusions prevented excessive bleeding.
      The literature is reviewed and management with platelet transfusions is
      discussed.

PMID- 8545294
TI  - Systemic lupus erythematosus presenting as effuso-constrictive pericarditis.
AB  - We describe a 62-year-old woman in whom systemic lupus erythematosus presented as
      life-threatening effuso-constrictive pericarditis. Surgical drainage of the
      pericardium was required and the patient made a satisfactory recovery. At six
      months follow-up, while taking hydroxychloroquine and a non-steroidal anti
      inflammatory agent, she remains well.

PMID- 8545295
TI  - Battered granny or spontaneous fractures? A legal dilemma.
AB  - A 70-year-old woman was admitted from a local nursing home with extensive
      bruising and bilateral hip discomfort. The referring doctor had reported the
      possibility of elder abuse to the police. Full examination showed that
      osteomalacia, precipitated by a poor diet and lack of exposure to sunlight, was
      sufficient to explain the patient's condition. Caution is recommended in
      diagnosing elder abuse until other possibilities have been excluded.

PMID- 8545296
TI  - Spontaneous regression of pulmonary mucormycosis.
AB  - A case of pulmonary mucormycosis with spontaneous resolution is presented. The
      patient had no known underlying predisposing disease.

PMID- 8545297
TI  - Haemopneumothorax.

PMID- 8545298
TI  - An abdominal cyst.

PMID- 8545299
TI  - Fatal hepatotoxicity associated with 6-mercaptopurine therapy.

PMID- 8545300
TI  - US residency programme.

PMID- 8545301
TI  - Changing nothing, changing everything.

PMID- 8545302
TI  - Sensitizing nurses for a changing environmental health role.
AB  - This paper traces the evolution of a broader environmental health role for
      nursing by focusing on the health effects of exposure to environmental pollutants
      and of global environmental change. This evolving role is reviewed through the
      examination of selected community health nursing texts published during the last
      several decades. Key role strategies based on this expanded and evolving
      environmental role are proposed. Finally, a survey is described that is intended
      to heighten awareness of personal and professional attitudes and behaviors
      related to the environment.

PMID- 8545303
TI  - Community partnership primary care: a new paradigm for primary care.
AB  - Primary care has become the focal point of health care reform. For too long
      primary care has been narrowly conceptualized as office-based care for common
      problems of individuals. In this article, a nurse practitioner describes a new
      model for primary care, community partnership primary care (CPPC), which moves
      beyond typical primary care practice to create what may be a new paradigm for
      primary care. This proposed new paradigm moves beyond older models of primary
      care into new dimensions of practice. The CPPC model emphasizes new roles for
      clinicians and a unique goal to foster the empowerment of individuals, families,
      and community. Innovative features of the CPPC model include blending a clinical
      role with a new area of practice called community practice. CPPC emphasizes new,
      innovative roles for nurse practitioners and nurses in community development and
      community empowerment activities. A 4-year funded project permitted the
      development and implementation of the CPPC model in an urban Hispanic community.
      This article provides an overview of the CPPC model and the initial steps of
      model implementation.

PMID- 8545304
TI  - Characteristics of pregnant women, utilization, and satisfaction with prenatal
      services in St. Petersburg, Russia.
AB  - A descriptive study with a convenience sample of 47 subjects drawn from two
      birthing houses was conducted in St. Petersburg, Russia, under the auspices of
      the World Health Organization Healthy Cities Project. Data were collected with a
      self-administered questionnaire given to women in birthing houses after delivery
      and prior to discharge. Subjects ranged in age from 16 to 38 years. Sixty-one
      percent of women began prenatal care within the 1st trimester, 35% within the 2nd
      trimester, and 2% received no prenatal care. Younger women were more likely than
      older women to start prenatal care in the 1st trimester, but received less
      teaching by health care providers. Younger women also expressed more stress and
      need for counseling. In addition, 83% of low-birthweight babies were born to
      younger women. These findings indicate a focus by health care personnel on older
      pregnant women, although younger pregnant women were at higher risk for poor
      pregnancy outcome. The strongest statistically significant correlations were
      found among the patient satisfaction variables, indicating that satisfaction with
      prenatal services may influence when women begin prenatal care services.

PMID- 8545305
TI  - Effects of sustained nurse/mother contact on infant outcomes among low-income
      African-American families.
AB  - This study examined the effect on infant morbidity and mortality of sustained
      nursing contact with mothers of healthy infants who are considered medically low
      risk but socially are at high risk due to poverty, low maternal education, and
      parenting at an early age. A quasi-experimental approach using a pretest-posttest
      design was used to evaluate the effect of the sustained nursing contact
      intervention (N = 97) compared with the instructions traditionally provided to
      the mothers of such infants (N = 48). In general, intervention and control
      infants did not differ on variables measuring health and development, morbidity,
      incidence of accidents, utilization of health care services, or immunization
      rates. Intervention infants scored significantly higher on advanced gross motor
      skills and had significantly fewer upper respiratory symptoms at the final visit.
      Highest morbidity was experienced by infants of teenaged mothers in the control
      group who had more than one infant. It was concluded that sustained nursing
      contact during the first eight months of infant life was beneficial to low-income
      African-American mothers, especially teenaged mothers with more than one infant.
      Infant morbidity and mortality were lower in both groups than would have been
      expected for their risk level, indicating that even minimal sustained nursing
      contact enhances outcomes of healthy infants at high risk for mortality and
      morbidity due to social factors.

PMID- 8545306
TI  - Diversity in the rural poor: differences between households with and without
      telephones.
AB  - Differences between households with and without phones in the United States as a
      whole are well documented, but these differences, and their implications for
      nursing practice and research, have received little attention in nursing
      publications. This article 1) reviews findings from national studies of these
      differences and 2) reports on a nursing study that examined such differences
      specifically in a random sample (N = 2,053) of low-income families having
      children eligible for but not using the well-child services of the Medicaid
      program in rural North Carolina. The study was part of a randomized trial of
      nursing interventions to encourage parents to use these services. The analyses
      reported herein focus on how families with and without phones differed in health
      related characteristics and in responses to the interventions. The findings have
      relevance for public health nurses conducting outreach or research with similar
      low-income families, even when the outreach or research methods do not involve
      phone contact.

PMID- 8545307
TI  - Development of the home care client satisfaction instrument.
AB  - Client (patient) satisfaction has been studied extensively in the health care
      sector, yet those receiving home health care services have been the focus of few
      studies. The purpose of this study was to test the reliability and validity of
      the Home Care Client Satisfaction Instrument (HCCSI). A total of 400 clients,
      randomly selected from 20 randomly chosen home care agencies in one state,
      completed the HCCSI and demographic form. Most respondents were older adults with
      multiple health problems and their families or informal support systems. Since
      data were skewed, item analysis was used. The revised instrument (HCCSI-R) is
      unidimensional and includes 12 items rated on a 5-point Likert scale measuring
      specific aspects of care. In addition, there are three global measures of
      satisfaction rated on a 10-point scale. All items except one had significant item
      total correlations greater than .59. The total score correlates with likeliness
      to recommend the agency to others (.37, p = .0001), showing some evidence for
      criterion-related validity.

PMID- 8545308
TI  - What is known about the health of rural homeless families?
AB  - Families represent the fastest-growing subgroup of the homeless population. Most
      of the research has focused on urban homeless families and not on rural homeless
      families. The purpose of this study was to describe the characteristics and
      health of rural homeless families in Ohio. A descriptive cross-sectional design
      was used to study 76 families who had 125 children under 12 years of age. An
      interview schedule, the Denver Developmental Screening Test (DDST), the Child
      Behavior Checklist (CBCL), and the SCL-90-R were used to collect data. The
      majority of the mothers perceived themselves and their children as having no
      physical health problems. Twenty-four of the children were behind on their
      immunizations. Forty-four (52%) of the children under 6 years of age had DDST
      scores that indicated they might have developmental lags and 15 of the children
      over 4 years of age had CBCL scores that indicated they might have behavioral
      problems. The reported use of illegal drugs, alcohol, and cigarettes was high for
      this group of mothers. Strategies are included that nurses can use in working
      with rural homeless families.

PMID- 8545309
TI  - Tuberculosis health education. Needs in homeless shelters.
AB  - Tuberculosis has reemerged as an important public health concern, particularly
      with the rise in multi-drug-resistant strains. The homeless are at increased risk
      for infection, for active disease, and for incomplete treatment. Public health
      authorities have recommended that tuberculosis health education materials be
      developed specifically for residents and staff of homeless shelters. In this
      study, a diverse sample of 20 adult homeless-shelter residents responded to open
      ended questions regarding 1) their knowledge of tuberculosis and tuberculosis
      screening and treatment, 2) their perceptions of access to health care services
      related to tuberculosis, and 3) their views of health education regarding
      tuberculosis. The majority of the subjects had limited knowledge of tuberculosis
      and of screening and treatment for the disease. Many had misconceptions about the
      disease, particularly regarding its transmission. An analysis of the subjects'
      responses within the framework of the Health Belief Model indicated that basic
      tuberculosis health education programs for residents of homeless shelters are
      needed. The study findings indicated that a small-group educational format
      utilizing written materials and video aids might be most effective.

PMID- 8545310
TI  - Causes of alcoholism: a qualitative study of traditional Muscogee (Creek)
      Indians.
AB  - Traditional Native American people are experiencing serious health, economic, and
      social problems resulting from alcoholism. Native Americans maintain a worldview
      of health and illness that conflicts with the dominant culture's approach to
      treatment. The purposes of this study were to describe the health beliefs of
      traditional Muscogee (Creek) Indians concerning the causes of illness and learn
      how these beliefs relate to alcoholism. The researchers conducted in-depth
      interviews of 55 traditional Muscogee (Creek) participants to learn traditional
      beliefs about illness and alcoholism. Data were analyzed using content analysis.
      Results indicate that both illness and alcoholism are perceived as having natural
      and unnatural (supernatural) causes. A challenge facing nurses is how to provide
      culturally sensitive care when clients' and nurses' beliefs about the cause of
      alcoholism may be in conflict. The authors discuss preservation, accommodation,
      and repatterning of health care beliefs as a basis for planning culturally
      sensitive nursing care.

PMID- 8545311
TI  - Using critical feminist principles to analyze programs for low-income urban
      women.
AB  - Public health nurses are committed to promoting the health of vulnerable
      populations, including the economically disadvantaged. One of the perspectives
      that can be used to work with low-income women is feminist theory. In this paper,
      we analyze program descriptions from 45 community agencies whose services are
      accessed by urban low-income women. The purpose of the analysis is to identify
      congruence between agency programs and selected feminist principles. As a result
      of the content analysis, empirical referents and examples were identified for
      each principle. Public health nursing programs can incorporate feminist
      principles by responding to the perspectives of the vulnerable and facilitating
      their efforts to change the conditions that led to their vulnerability. Questions
      are presented that could guide public health nurses in stimulating reflection and
      in facilitating dialogue in the process of developing programs for low-income
      women.

PMID- 8545312
TI  - A study of public health nursing directors in state health departments.
AB  - Public health nurses make up the largest single category of public health
      manpower, but confusion over where and how public health nurses should function
      continues. The purposes of this study were to describe the current structure of
      public health nursing in state health departments in the United States, and to
      note whether this structure had changed over the last 5 years. Data were
      collected through a survey sent to each of the 50 U.S. State Health Departments.
      Forty-eight percent of the 50 states responded to the survey. From the results,
      we can conclude that there is currently no uniform description of what states
      expect of their state nurse directors, even though these individuals lead the
      largest portion of the public health workforce. The public and the public health
      system place a large, but often unwritten and unspoken, expectation on public
      health nurse leaders, but in recent years erosion has occurred in public health
      nursing in many states. Public health nursing is well positioned to provide
      leadership under health care reform. The challenge now facing public health
      nursing leaders is to maintain or create the infrastructure, as well as the
      organizational culture, to maximize these opportunities.

PMID- 8545313
TI  - [Indications for celioscopic surgery in children].

PMID- 8545314
TI  - [Granular cell tumors. Rare tumors of the neurohypophysis].
AB  - Granular cell tumours of neurohypophysis are rare. These tumours are more often
      encountered as incidental autopsy findings seen in up to 17% of unselected adult
      autopsy cases. There are few reports of parasellar granular cell tumours large
      enough to cause symptoms. We present three cases of neurohypophysis granular cell
      tumour and a review of the literature. In one patient, the asymptomatic granular
      cell tumour was incidentally discovered at surgical removal of a corticotroph
      microadenoma. The remaining 2 patients had a symptomatic tumour which caused
      neurological symptoms such as visual disturbance and headaches and endocrine
      disorders such as hypopituitarism or hyperprolactinaemia. In these 2 cases,
      computerized tomography showed a well-circumscribed, contrast-enhanced,
      intrasellar and suprasellar mass. Magnetic resonance imaging demonstrated an
      isointense gadolinium-enhanced mass in T1-weighted images. Transsphenoidal
      partial resection was performed and histology was interpreted as a granular cell
      tumour. The immunohistochemical study was positive for glial fibrillary acidic
      protein (GFAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and
      positive for S100 protein and vimentin in both tumours but negative for CD68. The
      histogenesis of neurohypophysis granular cell tumours is still controversial but
      ultrastructural and immunohistochemical studies support the theory that they may
      arise from pituicytes, the glial cells of neurohypophysis. Management of these
      benign, slow-growing, tumours is based mainly on neurosurgical resection. Data
      from the literature do not support a beneficial effect of postoperative radiation
      therapy on postoperative recurrences.

PMID- 8545315
TI  - [Vascular and/or cardiac manifestations of type IV Ehlers-Danlos syndrome. 9
      cases].
AB  - Type IV Ehlers-Danlos syndrome, a rare disease caused by abnormal synthesis of
      type III collagen, often leads to vascular fragility. We report 9 cases (6 men
      and 3 women, mean age 35 years). For 7 of the patients, the inaugural signs were
      arterial complications including haemoperitoneum in 2 patients with multiple
      aneurysmal dystrophy of the abdominal arteries, one case of ruptured subclavian
      artery, two dissections of the renal artery, one case with rupture of a cerebral
      aneurysm, one rupture of the mesenteric artery and a haematoma after arterial
      puncture. Other vascular manifestations were acrosyndrome (n = 4), varicose veins
      (n = 3), and prolapsus of the mitral valve (n = 2). In addition, 8 of the 9
      patients presented extravascular signs. There was a history of familial disease
      in 5 cases. Pregnancy was completed to term in three patients: a cesarean section
      was required in one case and intra-uterine growth retardation was seen in 2.
      Morbidity was important with hemiparesia, blindness and paraparesis sequellae.
      One patient died from haemorrhage. This series of patients with type IV Ehlers
      Danlos syndrome illustrates the severity of this disease whose prevalence is
      often underestimated. The disease is transmitted by autosomal dominant
      inheritance, underscoring the importance of familial testing for early diagnosis.
      Clinicians should be aware of the vascular manifestations and avoid invasive
      punctures or operations except in exceptional indications.

PMID- 8545316
TI  - [Thyroid metastases from cancer of the kidney. Two cases].
AB  - Non-thyroid cancers rarely metastases to the thyroid gland. Metastases can be
      divided into those with clinical expression and those identified at necropsy.
      Symptom producing thyroid metastases are usually due to a primary renal cell
      cancer. We report two cases of thyroid metastasis of a clear cell renal
      carcinoma. In the first case, an 82-year-old woman presented with an enlarged
      thyroid gland. This inaugural element led to the diagnosis of thyroid metastasis
      and identification of recurrent renal cell carcinoma which had been treated by
      radiotherapy 24 years earlier. After radiotherapy for a concomitant pulmonary
      metastasis, the patient is in good general health with no signs of recurrence. In
      the second case, increased thyroid volume led to signs of compression in a 71
      year-old man. The pathology report after left lobular thyroidectomy suggested
      trabecular adenoma or metastasis of a clear-cell primary tumour. Abdominal CT
      scan revealed a 3.5 cm tumour found to be a clear-cell renal carcinoma at
      nephrectomy. Another osteolytic metastasis to the femur was also observed three
      months after surgery. The patient is in good health 15 months after the initial
      diagnosis. The significance of thyroid metastasis of renal cell carcinoma would
      vary according to the different cases reported in the literature with survival
      ranging from 32 months to 3-7 years after surgical exeresis. Prognosis would thus
      not appear to be as poor as for thyroid metastasis from other primary tumours.

PMID- 8545317
TI  - [Nonketotic hyperglycemic coma induced by somatostatin in an AIDS patient].
AB  - A 33-year-old woman with AIDS was treated with somatostatin (continuous infusion
      6 mg/day) for intractable diarrhoea. Improvement was insufficient and the dose
      was increased to 12 mg/day 5 days later. Hyperosmolar non-ketotic coma occurred
      two days later (blood glucose 53 mmol/l, bicarbonate 8 mmol/l, pH of arterial
      blood 7.2). Search for urinary ketones was negative. Klebsiella pneumonia was
      isolated in the urine sample. Somatostatin was withdrawn and the patient improved
      with parenteral nutrition and intravenous insulin. Glucose tolerance was verified
      after recovery and was normal. Somatostatin is known to impair glucose tolerance
      and as shown in this case should also be recognized as a cause of hyperosmolar
      non-ketotic coma. Increasing use of somatostatin, particularly in HIV patients
      often given other hyperglycaemia inducing drugs such as didanosine, pentamidine,
      dapsone, and phenytoin should be accompanied with careful monitoring of blood
      glucose levels.

PMID- 8545318
TI  - [Extrinsic allergic alveolitis of occupational origin].
AB  - Occupational factors encountered in farming and other agricultural activities
      produce a particular risk for respiratory diseases. For some, such as extrinsic
      allergic alveolitis, diagnosis depends upon a range of epidemiological, clinical,
      radiological and immunological arguments. Farmer's lung is one of the most common
      form of extrinsic allergic alveolitis. Bird breeder's lung is another, the list
      is long. The environmental allergens likely to affect alveoli and interstitial
      tissues have been identified, but simple detection of antibodies does not
      constitute a pathognomonic criterion of extrinsic allergic alveolitis. Co-immuno
      electrodiffusion is a rapid and sensitive technique for the demonstration of
      remarkable precipitating systems of extrinsic allergic alveolitis. This
      investigation enables subjects who really have the disease to be distinguished
      from contact subjects. Diagnosis is important to prevent development of a
      disabling and irreversible pulmonary fibrosis.

PMID- 8545319
TI  - [Postpartum hemorrhage. Current management].
AB  - Post-partum haemorrhage is one of the major worldwide causes of maternal
      mortality. Better knowledge of risk factors should limit its incidence and short
      term hazards. In case of excessive bleeding, classical therapeutic means continue
      to be of major importance. If unsuccessful, modern methods including injections
      of prostaglandins, vascular ligations, and arterial embolization, should be
      employed, preserving future fertility.

PMID- 8545320
TI  - [Biclonal gammapathy in type I Gaucher disease].

PMID- 8545321
TI  - [Vulvar localization, first metastatic site of a lobular carcinoma of the
      breast].

PMID- 8545322
TI  - [Myocardial infarction and cerebrovascular accident complicating papillary
      elastofibroma of the mitral valve].

PMID- 8545323
TI  - [Peritoneal sarcoidosis. A case].

PMID- 8545324
TI  - [Facial diplegia as an initial symptom of Gayet-Wernicke encephalopathy].

PMID- 8545325
TI  - [Schnitzler syndrome with stable course over a 18-year period. Report of a case].

PMID- 8545326
TI  - [Thrombocytopenia and serology for the emergency diagnosis of imported malaria].

PMID- 8545327
TI  - [Primary malignant tumor of the breast. Monitoring after treatment].
AB  - The appropriate follow-up of primary breast cancer patients is a controversial
      topic: an intensive surveillance is the rule for many oncologists, but the
      beneficial effect of this attitude has never been demonstrated. Two consensus
      conferences focused on this issue, both discouraged the routine use of laboratory
      tests, chest X-ray, radionuclide bone scan or liver echography which involve a
      high financial cost. For these routine investigations the sensitivity to detect
      recurrence is less than 5%. History and physical examination remain the best
      methods to detect a recurrence, and mammogram is helpful for detecting recurrent
      disease in the treated breast or a new primary cancer in the controlateral
      breast, which both are curable. The purpose of intensive follow-up is earlier
      detection of recurrence in order to treat as early as possible, but two
      randomized studies failed to demonstrate a survival benefit in 2600 patients.
      However with current treatments, only a follow-up study including a very large
      number of patients could detect a survival difference. The demonstration of an
      intensive follow-up benefit is similar in screening studies where it is
      recommended to use the most predictive, the less toxic and the less expensive
      test. Serum C.A. 15.3 level which best anticipates diagnosis in follow-up is one
      of the best candidates to be used in a randomized study.

PMID- 8545328
TI  - [Acute ischemic liver].
AB  - Ischaemic hepatitis, a condition to be distinguished from cardiac liver or stasis
      cirrhosis, can occur as an acute episode in patients with advanced stage
      congestive heart failure. The mechanism is massive necrosis in the central
      lobules resulting from acute hypoxia when low cardiac output reduces oxygen
      supply further aggravating the underlying condition of congestion due to poor
      venous outflow. We report 4 cases which illustrate the difficulties in diagnosis
      and treatment. All four patients (age range 79-86 years) were seen in an
      emergency situation caused by an acute drop in cardiac output aggravating their
      underlying heart failure. Clinical signs included jaundice, oligouria, abdominal
      pain and cardiovascular shock. The first element suggesting the diagnosis of
      ischaemic hepatitis was a sudden and massive peak in transaminase levels (> 20
      times normal) which rapidly returned to normal. Prothrombin and fibrinogen levels
      fell rapidly and functional renal failure was present in all cases. Viral
      serology was negative and no hepatotoxic drugs could be incriminated. Despite
      symptomatic intensive care one patient died on day 15 due to cardiovascular
      shock. Enzyme movements, together with the lack of evidence for another cause, is
      the key to diagnosis of acute ischaemic hepatitis which thus is often established
      after the emergency situation has been controlled. Initially, viral hepatitis or
      drug-induced hepatotoxicity may be suspected, especially if the episode of low
      cardiac output goes unrecognized. Cases with signs of encephalopathy may also be
      difficult to distinguish from fulminating hepatitis and would be the only
      indication for needle biopsy in this acute situation. Outcome is generally
      unfavourable with mortality at 6 months estimated at 50%.

PMID- 8545329
TI  - [Borderline tumors and cancers of the ovary. Laparoscopic-surgical evaluation].
AB  - OBJECTIVES: Benign cysts of the ovary can now be correctly treated with
      laparoscopic surgery, but it is difficult to confirm the benign nature of the
      suspected formation. Thus, the major risk of the laparoscopic surgery is the
      dramatic consequences in case of malignancy as reported in several cases in the
      literature. We conducted a survey to evaluate this risk. METHODS: A retrospective
      multicentric survey of laparoscopic procedures performed for a diagnosis of
      lesions of the annexes or cyst of the ovary was conducted. Forty-four centres
      reported a total of 7,122 laparoscopic procedures, including 5,307 in which
      laparoscopic surgery was performed. Laparoscopic treatment included puncture
      (21.3%), partial exeresis (51.3%) and complete exeresis (25.6%). Conversion to
      laparotomy was required in 20 cases (25.6%). A complementary surgical procedure
      was needed after the laparoscopic procedure within a delay of 78 days in 49 cases
      (58%). Laparoscopy was the only procedure used in 16% of the cases. RESULTS:
      Pathology reports of the surgical specimen indicated malignant lesions of the
      ovary in 78/5, 307 cases (1.47%) including 60 borderline tumours and 18 cancers.
      Among these 78 cases, preoperative work-up and laparoscopy had led to a diagnosis
      of a benign lesion in 17 (21.8%). Among the 49 cases with secondary surgery, a
      more advanced FIGO (International Federation of Gynaecology-Obstetrics) stage was
      observed in 11 (i.e. 8.3% of the 78 malignant cases) compared with the initial
      assessment. CONCLUSION: These findings demonstrate that it is not rare to
      discover the malignant nature of an ovarian tumour after initial laparoscopic
      treatment of a formation initially diagnosed as benign. Such accidents are the
      result of insufficient security in risk evaluation before laparoscopy. Whenever
      there is even a minimal risk of malignancy, laparotomy must be performed as the
      procedure of choice.

PMID- 8545330
TI  - [Circulating antigliadin antibodies. Prevalence in a diabetic (type 1 or 2) and
      non diabetic adult population].
AB  - OBJECTIVES: The level of circulating antigliadin antibodies is an essential
      element in diabetic patients with signs of coeliac disease. Intolerance to gluten
      can disrupt glucose regulation leading to greater risk of hypoglycaemia. Search
      for antigliadin antibodies could be a routine test in diabetics. METHODS: Plasma
      gliadin antibodies were measured by immunoenzymatic assay in adult subjects: 80
      type 1 diabetics, 80 type 2 diabetics, 80 non diabetics without auto-immune
      disease. RESULTS: IgA antibodies were present in 6 type 1 diabetics (7.5%), 8
      type 2 diabetics (10%) and 6 non-diabetics (7.5%). Anti-reticulin and anti
      endomysium antibodies were measured in type 1 diabetics with antigliadine
      antibodies. They were present only in one patient (Tunisian) who suffered from a
      coeliac disease. CONCLUSION: In France, the prevalence of coeliac disease is very
      low. Antigliadin antibodies measurement is justified only in patients with
      clinical and/or biological symptoms of coeliac disease.

PMID- 8545331
TI  - [Arterial pressure and urinary excretion of albumin in adults with sickle cell
      disease].
AB  - OBJECTIVE: The increase of urinary albumin excretion could be associated with
      morbidity in patients with sickle cell disease. The objective of this study was
      to evaluate the relation between blood pressure and urinary albumin excretion,
      and to estimate the prevalence of hypertension according to the level of urinary
      albumin excretion. METHODS: A cross-sectional study was carried in 77 patients
      with sickle cell disease (48 patients with haemoglobin SS, 29 with haemoglobin
      SC) et 30 controls with haemoglobin AA. The patients with sickle cell disease
      were divided into 3 groups according to urinary albumin excretion: less than 30
      mg daily (group I: normoalbuminuria); from 30 to 300 mg daily (group II:
      microalbuminuria); above 300 mg daily (group III: macroalbuminuria). All AA
      selected controls had normoalbuminuria (group IV). RESULTS: In normoalbuminuric
      patients, the average of blood pressure was significantly lower in patients with
      sickle cell disease than in controls (respectively 115.0 +/- 8.1 vs 132.1 +/-
      15.1, p = 4.10(-6) for systolic pressure and 67.2 +/- 8.0 vs 78.8 +/- 9.8 mmHg, p
      = 10(-4) for diastolic pressure). There was a positive relation between urinary
      albumin excretion, even moderate (values < or = 300 mg daily) and blood pressure
      in SS patients (r = 0.40, p < 0.02 for systolic and r = 0.54, p < 0.01 for
      diastolic pressure) and in SC patients (r = 0.74, p < 0.001 and r = 0.58, p <
      0.01). The prevalence of hypertension was 0% in group I, 25% in group II and 66%
      in group III. CONCLUSION: The positive association between blood pressure and
      urinary albumin excretion suggests that the latter should be taken into account
      in sickle cell disease's follow up.

PMID- 8545332
TI  - [Large eventrations: deep extensive cleavage of the abdominal wall and prosthetic
      repair].
AB  - The objective for surgical repair of major defects of the abdominal wall is an
      anatomical reconstruction and reinforcement with a support prosthesis. Wall
      reconstruction should be obtained without tension. This requires deep extensive
      cleavage so the deep musculo-aponevrosis can be advanced approximately 10 cm.
      This manoeuvre is anatomic and preserves vascularization and innervation. A
      prosthesis covers the orificies and reinforces the anatomic construction. In
      peripheral defects, cleavage is necessary for closure. The prosthesis is anchored
      on deep solid structures (ribs, iliac crests) guaranteeing solidity. In a series
      of 252 operated patients, abdominal wall solidity was achieved in 91% of the
      cases with a mean follow-up of 2 to 13 years. Mortality was 1.2% and morbidity
      8%, emphasizing the importance of rigorous indications. Intensive preparation
      including the Goni Moreno pneumoperitoneum is required for surgery in all major
      abdominal wall defects.

PMID- 8545333
TI  - [Liver transplantation in children].
AB  - The need for paediatric liver transplantation, which in most paediatric series is
      the remedy for biliary atresia after Kasai's operation has failed, is not
      sufficiently covered by organ retrieval at the present time. In most cases,
      survival after liver transplantation in children is approximately 80%. Mortality
      is still high due to intra-operative complications in most cases. Morbidity is
      related to vascular complications as well as to different types of infections
      which occur in nearly all the children. After the initial period, growth in most
      children returns to normal with normal physical and intellectual development.
      There remain a number of questions concerning the future of liver transplantation
      in children. What are the limits for proper indications and contraindications?
      What is the risk of life-long immunosuppressive treatment? Are there alternative
      modalities of treatment other orthotopic liver transplantation? It must be
      admitted that before progress has provided answers to these questions and a
      better understanding of the aetiology of many congenital or metabolic diseases in
      children as well as a better means of treatment or prevention, that the need for
      liver grafts in children will continue to rise as a consequence of its own
      success. One point must be emphasized, since we are concerned with very young
      children, care should always be given by specially trained health care providers.

PMID- 8545334
TI  - [First cases of resistance of Pediculus capitis Linne 1758 to malathion in
      France].

PMID- 8545335
TI  - [Plication or stenosis of the right coronary artery? Diagnosis by filling the
      right ventricle].

PMID- 8545336
TI  - [Primary hepatic actinomycosis: current management of a rare disease].

PMID- 8545337
TI  - [Seroprevalence of cytomegalovirus infection in human immunodeficiency virus
      infected subjects].

PMID- 8545338
TI  - [Acute hemorrhagic diarrhea caused by Klebsiella oxytoca: associated with
      virginiamycin?].

PMID- 8545339
TI  - [Synchronous cancers. A case with three localizations: rectal cancer associated
      with familial polyposis, breast cancer and adrenal gland cancer].

PMID- 8545340
TI  - [Horton disease and aortic involvement].

PMID- 8545341
TI  - [State of shock and bilateral paralysis of the III cranial nerve revealing
      necrotic pituitary macroadenoma].

PMID- 8545342
TI  - [Early diagnosis and screening of cancer of the prostate].
AB  - It is obvious that digital rectal examination and assay of prostate specific
      antigen are required for all patients presenting signs of prostatism, but the
      true benefit of such an attitude for all patients is a matter of much
      controversy. We do know that the incidence of prostate cancer is rising faster
      than any other cancer and that the cause of death in approximately 3% of the male
      population over 50 years will be cancer of the prostate. Yet despite this risk,
      and due to the lack of satisfactory registries, the prevalence of the disease
      still remains unknown. A well-conducted mass screening programme could be
      expected to uncover prostate cancer in approximately 6% of the population, which
      would mean that in the French male population in the 55-70 year range, 348,000
      cases would be diagnosed. Assuming that 70% of them would have a localized form
      theoretically accessible to curative treatment (radical prostatectomy or
      radiotherapy), the current mortality for prostatectomy (1 to 2%) would mean that
      at least 2,500 persons would die during the perioperative period. The question of
      psychological impact of a general screening programme and its cost are other
      considerations of importance. Under these conditions, can a mass screening
      programme be proposed? In France, the answer today appears to be no. The
      arguments in favour of early diagnosis are insufficient for mass screening and
      will remain so until a certain number of basic questions concerning the efficacy
      of treatment, the cost-benefit ratio of screening, and the psychological impact
      of early diagnosis are resolved.

PMID- 8545343
TI  - [Treatment of metastatic cancer of the prostate].
AB  - Rising incidence, resulting from diagnosis together with the increasing age in
      the population, and high mortality combine to make cancer of the prostate a
      leading cause of death in men. Despite early, and unfortunately overly
      optimistic, hopes placed in oestrogen therapy, management of patients with
      metastatic cancer of the prostate remains one of the major challenges facing
      urologists. For stage D1 (invasion of the iliac nodes), systemic treatment is
      required, based on androgen deprivation, with five years disease free survival
      ranging from 55% to 95%. Radical prostatectomy is not indicated in cases of
      pathologically confirmed macroscopic nodal involvement, but the question remains
      controversial for patients with microscopic metastases. Pelvic radiotherapy at
      "curative doses" is not indicated because of the lack of any improvement over
      hormone therapy alone. Controversies still exist about timing of androgen
      deprivation (early or deferred endocrine treatment) either for stage D1 or stage
      D2 asymptomatic patients, but controlled studies are ongoing. Immediate endocrine
      therapy is however clearly indicated in stage D2 symptomatic disease and leads to
      improvement of symptoms (mainly bone pain) in up to 80% of patients. When there
      is spinal cord compression adding corticosteroids can be useful; surgery or
      radiotherapy are indicated particularly in cases of vertebral instability or
      neurological involvement. Current protocols are based on maximal androgen
      deprivation combining medical or surgical castration and anti-androgens.
      Prognosis is very poor at relapse despite hormone therapy (stage D3). Survival
      rate at 1 year is only 50%. It is essential that anti-androgens be withdrawn at
      this time since clinical improvement can be observed in some patients (anti
      androgen withdrawal syndrome). None of the second line treatments (hormonal or
      chemotherapy) have led to any improvement in survival time. Treatments only
      alleviate patient discomfort and improve quality of life. The lack of progress
      over the last 50 years in the treatment of advanced stage cancer of the prostate
      means that the only way to cure future patients will be conditioned by early
      diagnosis and treatment during the less advanced stages.

PMID- 8545344
TI  - [Prostate-specific antigen or PSA. Facts and probabilities].
AB  - The introduction of prostatic specific antigen (PSA) assay as an organ-specific
      marker has totally modified our approach to diseases of the prostate gland. PSA
      is an exocrine secretion of the normal epithelium of the prostate and any
      infectious, dystrophic or tumoural processes involving the gland can lead to an
      increased level in the blood stream. PSA is the most effective means of following
      the curative effect of treatment for prostate cancer. After radical
      prostatectomy, PSA should be undetectable with hypersensitive tests (detection
      threshold < 0.1 ng/ml) 6 weeks after the operation. The persistence or
      reappearance of the marker in the blood stream is a clear indication of
      recurrence. A drop off in PSA under laboratory normal levels is an effective
      marker of the efficacy of hormone treatment for metastatic cancer but does not
      signify cure. There are still several points of debate. Serum PSA does increase
      with prostate volume but there is no apparent linear relationship. PSA is an
      important factor in early diagnosis of prostate cancer but must always be
      interpreted in light of the patient's age. In patients treated for cancer of the
      prostate, PSA is insufficient to determine tumour extension. The relationship
      between the PSA level and prostate volume could be a way of suspecting cancer,
      but the operator-dependent results of echography hinder application. Finally,
      search for circulating secretory cells with reverse transcriptase polymerase
      chain reactions still requires validation, but could be used for assessing cancer
      extension.

PMID- 8545345
TI  - [Radical prostatectomy].
AB  - Radical prostatectomy can cure cancer of the prostate if the malignancy is
      localized within the gland and the patient has a life expectancy sufficiently
      long enough to appreciate efficacy. The expectations raised by this technical
      progress, particularly since the number of diagnosed cases is constantly on the
      rise, should however be tempered by questions concerning indications and
      therapeutic efficacy, pathology findings in surgical specimens, factors of
      prognosis and certain doubts about the quality of life, therapeutic alternatives
      and cost evaluation. 10-year survival after radical prostatectomy is 85% for
      localized (pT1 and pT2) forms and prostate specific antigen levels provide an
      easily accessible means of detecting recurrence. However, due to the insufficient
      sensitivity of imaging techniques, preoperative staging is generally
      underestimated compared with pathology reports. Postoperative incontinence is the
      major factor in quality of life after prostatectomy and has been estimated to
      concern from 0% to 26% of the patients. No comparative data is available to
      evaluate alternative treatment such as external radiotherapy. These observations
      emphasize the uncertain nature of current indications for radical prostatectomy
      and the importance of further research.

PMID- 8545346
TI  - [Non-surgical instrumental treatment of benign hypertrophy of the prostate].
AB  - Although surgery remains the treatment of reference for symptomatic benign
      hypertrophy of the prostate, the requirement for locoregional anaesthesia, the
      risk of complications and the major financial burden for the health care system
      have led to research into alternative therapies. Basically two categories have
      been developed, thermal and mechanical. The sensitivity of the hypertrophic
      prostate tissue to heat depends both on histology and blood flow. It is generally
      accepted that temperatures < 60 degrees C do not cause definitive tissue damage,
      that those > or = 60 degrees C lead to necrose of the coagulated tissue and > or
      = 100 degrees C cells are vaporized producing tissue debris. Currently,
      thermoablation (temperature > 60 degrees C) is the only thermal alternative which
      gives results within a range comparable with classical surgery. The more simple
      techniques (microwaves, focalized ultrasounds, interstitial radiofrequency waves,
      lateral or interstitial laser) have the disadvantage of aggravating
      symptomatology in certain patients, limiting indications. More sophisticated
      techniques (contact radiofrequency, contact laser) still need improvement to
      reach the level of surgery. Mechanical alternatives include resorbable and non
      resorbable stents and dilatation. Stents are a particularly promising route but
      have the inconvenience of being difficult to implant and sometimes leading to
      complications (infection, incrustation, calcification). Dilatation procedures
      have been tried for many years using various methods of control, but results have
      been disappointing to date. Surgery thus remains the reference treatment for
      benign hypertrophy of the prostate, but ongoing research emphasizes the need for
      successful alternatives.

PMID- 8545347
TI  - [Surgical treatment of benign hypertrophy of the prostate].
AB  - It has been calculated that 7% of the males living in France over the age of 65%
      will undergo a surgical procedure for benign prostatic hyperplasia within 5
      years. Currently approximately 65000 patients are operated every year. The mean
      age of the patients is 71.8 years with an incidence much lower than that observed
      in the United states where the mean age is 66 years. According to the reports of
      the 87th congress of urology, 10 to 20% of the patients are operated because of
      urine retention.

PMID- 8545348
TI  - [Medical treatment of benign hypertrophy of the prostate].
AB  - Surgery is obviously indicated in a patient with benign prostatic hypertrophy and
      severe signs of urine retention, infection, and a bladder with diverticles and
      calculi. Inversely the patient with minor dysuria and a normal upper urinary
      tract usually needs simple counselling. The major question is how to manage
      patients with intermediary symptomatology. Much emphasis has been placed on
      measurement of quality of life, but cannot be used to determine a therapeutic
      strategy. Indeed, there is no precise criteria for indicating medical treatment
      of benign prostatic hypertrophy. Randomized, controlled and well conducted
      studies have shown however that the beneficial effect of certain drugs is greater
      than the placebo effect, but there is no common criteria to determine what degree
      of improvement justifies prescription. In addition, the cost of medical
      treatment, in terms of overall health care cost for the society, must be taken
      into consideration. Despite these drawbacks, several drug classes--plant
      extracts, alpha-blockers, 5-alpha-reductase inhibitors--have been used with
      confirmed effectiveness. The spectacular advances in pharmacology in the field of
      benign prostatic hypertrophy will undoubtedly have an impact on other areas of
      research, but the medical, economic and ethic justification of prescribing
      "comfort" drugs is one of the major challenges facing urologists today.

PMID- 8545349
TI  - [Antibiotic prophylaxis in urology].
AB  - There is little reason why the organism could benefit from the presence of micro
      organisms in the urine. In the case of severe infection, the consequences can be
      devastating, both for the health of the individual and for the overall effect in
      terms of health care costs. There is thus a clear need for a reduction in the
      number and severity of urinary tract infections by a strictly controlled, well
      planned, antibiotic prophylaxy. Beyond well-established rules concerning timing,
      duration, dose and, in certain cases, indications of antibiotics, there remains a
      number of questions yet to be fully understood. What is the ecologic impact of
      antibiotic prophylaxy? What is the original source of infection in patients
      undergoing multiple procedures? What is the relationship between serum
      concentrations and efficacy? What is the role of in situ germs and nosocomial
      agents? These and other questions require rigorously conducted research where not
      only urologists but also bacteriologists, infectiologists and public health
      specialists all have an important role to play.

PMID- 8545350
TI  - [Treatment of renal and ureteral lithiasis].
AB  - The advent of extracorporal shock wave lithotripsy has entirely changed
      management of patients with renal or ureter calculi. It is indicated in all types
      of calculi and generally used as first line treatment. Contraindications are
      exceptional: pregnancy, uncorrectable coagulation disorders. For staghorn calculi
      in the kidney, lithotripsy alone is only effective in 50% of the cases and is
      often completed or preceded by percutaneous nephrolithotomy. Classical surgical
      procedures may be required in complex cases. Success rate (complete stone free
      with none residual) with lithotripsy is higher for pelvic stones (70%) and small
      residual fragments are usually asymptomatic and rarely infected. There is still
      some debate over indications for ureteral calculi although use of in situ
      lithotripsy with an ureteral probe. The ureteroscopy is more effective for stones
      in the distal ureter. In all cases, the final factor in the management decisions
      is cost-effectiveness.

PMID- 8545351
TI  - [Treatment of stress urinary incontinence in women].
AB  - Involuntary urinary leakage due to a rise in abdominal pressure caused by stress
      (cough, laugh, change in position, walking, running or carrying heavy weight) is
      a clinical entity often experienced by women. Management can be based on physical
      therapy techniques, drugs or surgery but indications and results to be expected
      are still very largely debated. Cure of an underlying condition such as obesity,
      or chronic bronchitis may be sufficient in some cases and others may benefit from
      "preventive" physical therapy to reinforce the perineum after difficult pregnancy
      and delivery. Alpha-stimulating drugs have also been proposed to increase
      sphincter tone. Surgery gives the best results. Several procedures have been
      proposed, usually based on classical retropubic colposuspension and aponevrosis
      loops. Success rate is approximately 80 to 90% although the lack of a sufficient
      understanding of the underlying mechanism involved, makes it impossible to
      predict outcome. Results in women with recurrent incontinence are less
      satisfactory.

PMID- 8545352
TI  - [Treatment of stage I non-seminomatous germ cell tumors of the testis].
AB  - The incidence of germ-cell tumours of the testicle is approximately 4/100,000
      men. Approximately half of these have non-seminomatous tumours. Chemotherapy has
      made clinical cure possible in most patients with metastasis and good prognosis
      factors (small tumour volume and low or normal hormone markers). This observation
      has led to a modification of the treatment protocols for patients with stage I
      disease, i.e. normal imaging after orchidectomy and normal plasma levels of
      chorionic gonadotrophin and alpha fetoprotein. There are currently three
      acceptable ways of managing patients with stage I non-seminomatous germ-cell
      tumours of the testicle after orchidectomy: the wait and see approach generally
      adopted in Great Britain, retroperitoneal lymphadenectomy used in the United
      States, or as often proposed in France, adjuvant chemotherapy. The analysis of
      outcomes reveals that the risk of recurrence would be smallest with
      retroperitoneal lymphadenectomy or adjuvant chemotherapy while morbidity due to
      anejaculation would be greater with the former technique. In our opinion, a wait
      and see attitude combined with chemotherapy adapted for cases with a risk of
      extratesticular involvement would be justified both in terms of cost
      effectiveness and in patient comfort and psychological well-being. This protocol
      has been adopted by the Cancerology Committee of the French Association of
      Urology and is strongly encouraged.

PMID- 8545353
TI  - [Immunotherapy in metastatic cancer of the kidney].
AB  - Evidence accumulated over the last 15 years has clearly demonstrated that
      metastatic renal cell cancer is an excellent model of the effect of immunotherapy
      for the treatment of cancer. To date, at least 2 cytokines, interleukin-2 and
      alpha-interferon have been found to be effective. Objective response is obtained
      in 15 to 30% of the patients treated with interleukin-2 and 10 to 30% with
      interferon. Complete response can be achieved in 5% of the cases. Clinically, the
      best results are seen in patients in good general health and lung metastasis.
      Complete response for more than 5 years is often observed. Combination protocols
      with both cytokines and other combinations with infusion of activated lymphocytes
      have not shown to be more effective than one cytokine alone. It may be possible
      to obtain higher response rates by combining cytokines with chemotherapy
      protocols. Surgery still has a role to play however, particularly in patients
      with an isolate accessible metastasis. Among the perspectives for new
      immunotherapies, interleukin-12, a strong stimulator of the natural killer
      population is in phase II trials. Other possibilities include the use of
      selective populations of lymphocytes as adoptive immunotherapy or combinations
      using immunotherapy and surgery. Despite the enthusiasm generated by these new
      techniques, it is imperative to continue rigorous clinical trials in order to
      develop immunotherapy as a reliable routine treatment.

PMID- 8545354
TI  - [Conservative surgery in cancer of the kidney].
AB  - Partial nephrectomy is classically indicated in patients with renal cell cancer
      on a single kidney, although a certain amount of debate continues on surgical
      technique: simple enucleation or true partial nephrectomy. Incidence of
      multifocal tumours has been estimated at 6 to 19.6%. The crucial problem for the
      surgeon is to recognize satellite tumours pre- and peroperatively since it has
      been estimated that 4 to 10% of renal cell carcinomas contain a multifocal
      disease unrecognized during surgery. Is conservative nephrectomy acceptable for
      patients with a functional contralateral kidney? There are several arguments in
      favour of the technique: fortuitously discovered tumours are generally smaller
      and in a less advanced stage, morbidity after conservative surgery is low
      compared with total nephrectomy, nephron sparing improves long-term renal
      function and survival at 3 to 5 years is 95 to 100%. The fact that the risk of
      cancer on the contralateral kidney is small (1 to 2%) compared with the risk of
      local recurrence and the lack of sufficiently long follow-up in large series are
      negative arguments. Conservative nephrectomy must therefore be considered as the
      best solution when nephron sparing is essential. Total nephrectomy remains the
      reference treatment in other cases although the discussion remains open for cases
      with small (< 2.5 cm) tumours.

PMID- 8545355
TI  - [Renal graft].
AB  - After years of pioneering research and clinical applications, renal
      transplantation has now moved into the era of routine practice-the first line
      treatment for renal failure in more than 1500 new patients each year in France.
      Despite this success, transplantation is not a cure, it simply replaces one
      disease by another-immunodepression. As a result, over the next 20 years, 60% of
      the recipients will undoubtedly develop cancer. In addition, the life span of a
      transplanted kidney is shorter than that of the recipient. Consequently most of
      them will require a second graft 8 to 10 years after the first. Together with the
      development of new innovating immunology agents such as FK 506 and mycophenolate,
      for example, these current facts raise the challenging question of the future for
      renal transplantation. Will adequation between donors and recipients be achieved?
      Should we develop single organ transplantation units within our current
      nephrology-urology structures or create multiorgan units devoted solely to
      transplantation? And finally, will (or perhaps when will) progress in immunology
      completely control the problem of organ rejection? One technical point is also of
      interest. Being (with orthopaedic surgery) one of the rare indications where open
      surgery can be expected to continue over the next 20 years, renal transplantation
      units will play an essential role in training future surgeons.

PMID- 8545356
TI  - [Treatment of male infertility].
AB  - Progress in medically assisted procreation has made it possible to obtain an
      embryon with a single spermatozoid or even a single spermatid. But such advanced
      technology must not overshadow the basic principles of patient management since
      there are many other medical or surgical possibilities for improving male
      fertility. Although the physiological mechanisms leading to azoospermia are
      relatively well understood, many questions remain as to the origin of oligo
      asthenoteratospermia. Varicocela had been incriminated by many authors: in 25% of
      the cases, surgical care is followed by pregnancy. Other factors including
      autoimmunity, infection, environment and drugs also have an effect. Careful
      history taking can identify the main causes of male infertility before the
      problem of procreation occurs and in cases of definitive azoospermia the
      principles of management are relatively simple. The true problem is the fact that
      new techniques such as in vitro fertilization have acquired popularity in the
      general population but cannot be accepted as the gold standard by the medical
      community. It must not be forgotten that these artificial techniques cause a
      major psychological trauma to the couple and can lead to difficult situations
      (multiple pregnancies, extra embryos) with no totally satisfactory solution.

PMID- 8545357
TI  - [Why and how to measure the quality of life? Questions to be asked by the
      urologist].
AB  - Quality of life is not a question of fashion but rather a new perception of the
      effects of health care. Unfortunately, currently developed means of assessing
      health status only rarely englobe quality of life assessment and when they do,
      still need much improvement. Modelization is a difficult task and requires a long
      scientific approach. In order to achieve the goal of reliable quality of life
      assessment, the different professional colleges should work together with
      methodologists to identify assessment criteria and include them in future
      clinical research protocols.

PMID- 8545358
TI  - [Training of urologists].
AB  - Urologists in France are combining classical teaching programmes and innovative
      cooperative efforts to better train their future colleagues. Candidate urologists
      participate in a 2-year programme during the last year of the 5 year general
      surgery internship and an additional post-internship year. Courses in anatomy,
      infectiology, oncology, and tissue repair are given together with special courses
      in emergency surgery and urology. An innovative project developed by the French
      College of Urology invites trainees to participate in cooperative national
      seminars on a specific theme. Each seminar is proposed conjointly be at least two
      teams in different university hospitals. This provides fruitful exchange of
      techniques and opinions between teams and offers trainees a stronger trainer
      trainee relationship with a larger number of established leaders. The programme
      is regularly assessed by the College. These theoretical training sessions are
      completed by clinics in general and digestive surgery, orthopaedic surgery and at
      least 2 years in an urology clinic. The post-internship year is essential for the
      future urologist. As "chef de clinique" in an urology unit, he has immediate
      responsibility for patient care under the guidance of a senior and is
      progressively give total control of the most sophisticated procedure. The French
      College of Urology is currently examining proposals for determining accreditation
      criteria for teaching centres and continuous evaluation of the objectives for
      practical training within the framework of the associations of national
      urologists working together in the European Board of Urology.

PMID- 8545359
TI  - [Neurogenic bladder, 20 years later].
AB  - The therapeutic armamentarium--physical therapy, drugs, surgery--developed over
      the last 20 years now gives us the means of providing curative care to nearly all
      patients with manifestations of neuropathic bladder, meaning that the clinical
      examination and complementary tests must be conducted under strictly controlled
      conditions to identify the underlying mechanism. The examination of the perineum
      almost always reveals a defect when the origin is neurological but is often
      normal when gynaecologic or urologic factors are involved. Motor command, tonus,
      reflexes and sensitivity should all be carefully explored to distinguish between
      central and peripheral causes. Much progress has been made in complementary
      examinations. For example, nearly 100% of the neurological aetiologies can be
      identified with precision. Tests include electromyography of the perineum,
      measurement of the latency of the bulbocavernous reflex and that of the distal
      part of the internal pudental nerve. Complementary tests evaluating bladder and
      sphincter function include urine sediment with cytology, intravenous pyelography
      and echography of the urinary tract. Pressure measurements with cystomanometry,
      sphincterometry and flowmetry add further precisions. Whether the underlying
      mechanism of bladder dysfunction is purely neurological as is the case in many
      young patients with multiple sclerosis, spina bifida or caudia equina syndrome,
      results from several causes as in patients with Parkinson's disease and
      enlargement of the prostate, or is among the increasing number of post-radiation
      sequellae, the essential step is careful clinical examination and detailed
      interpretation of complementary examinations. Thus the wide range of techniques
      now available for the management of the neuropathic bladder can be adapted to
      each individual case according to the pathological processes causing the clinical
      manifestations.

PMID- 8545360
TI  - [Treatment of cystitis in women].
AB  - Acute cystitis is a benign curable condition which affects at least one out of
      every two women at least once in their life. In uncomplicated cases, urinalysis
      is usually unnecessary as a simple dip stick test is sufficient for diagnosis and
      prescription of a short antibiotic regimen (a single dose or a 3 day treatment).
      Complicated acute cystitis requires a more precise diagnosis and justifies
      urinalysis and imaging. Antibiotics adapted to germ sensitivity is prescribed
      until bacteriologically sterile urine is obtained (3 to 10 days). Associated
      malformations of the urinary tract or obstruction must be managed together with
      careful control of aggravating factors (diabetes) and personal hygiene. Recurrent
      cystitis, defined as at least 4 episodes, raises a certain number of problems.
      The casual germ varies, although Escheria coli is found in approximately 70% of
      the cases. Several factors favour recurrent cystitis including malformations of
      the urinary tract, lithiasis, bladder reflux, cystocele or modification of the
      urethral meatus. Other circumstances such as sexual relations, excessive vaginal
      hygiene, vaginal tampons and clothing habits may play a role. Antibiotics
      generally solve the problem, but mechanisms which would improve the organism's
      specific response are currently under study.

PMID- 8545361
TI  - [Treatment of erectile insufficiency].
AB  - Impotency, or impaired erectile function, affects approximately 10% of the adult
      males in France. The psychological consequences can have a major impact not only
      on the subject's sexual life but also his familial and professional
      relationships. The task facing the urologists is to carefully evaluate the
      patient's request for care and adapt treatment not only to the physiological
      situation but also the patient's psychological and social context. Several
      approaches have been developed. Search for an aetiology, excepting exceptional
      cases with a recognized organic origin, is often unsatisfactory due to the
      multifactor processes involved and the self-sustaining inter-relationship between
      the psychological impact and the physiological disorder. Sex therapy is aimed at
      reducing anxiety and helping the couple better understand their sexual
      relationship. Such behavioural counselling is particularly indicated in absence
      of organic disorders or as complementary therapy combined with medical or
      surgical treatment. The pharmacological approach relies on alphablockers or
      certain psychotropic drugs which have a moderate but real effect when taken
      orally. Local non-invasive applications of protaglandin E1 can also improve
      erectile function. The mechanism of intrapenial injections is to release the
      erectile smooth muscles. The most widely used drugs in France are papaverine,
      phentolamine and moxisylite as well as prostaglandin E1. Self-injections may be
      required in certain cases but are abandoned by about half of the patients after
      one or two months. Vacuum with a mechanical pump can produce a non-physiological
      erection but is rarely used in France. Surgical repair of arterial or venous
      disorders can also provide excellent, particularly long-term, results in
      carefully selected patients. Despite undeniable progress, the treatment of
      impotency remains a difficult therapeutic challenge, basically due to the large
      number of casual factors and their complex interactions.

PMID- 8545362
TI  - [Management of severe acute asthma in adults].

PMID- 8545363
TI  - Gastro-oesophageal reflux in children and nuclear medicine.

PMID- 8545364
TI  - [Selective indications of cardiac studies before aortic surgery].
AB  - OBJECTIVES: There is no consensus on heart explorations required before infra
      renal reconstruction surgery of the aorta. We proposed a selective approach in 81
      consecutive patients undergoing elective surgery. METHODS: Four clinical criteria
      were recorded: age over 70 years, diabetes mellitus and a clinical history of
      coronary artery disease or heart failure. RESULTS: For 23 patients (group 1),
      none of the criteria were positive. Surgery was performed in all without prior
      exploration. There was one death (4.8%) and one post-operative cardiac event
      (4.8%) in this group. The 58 other patients (group 2) had at least one of the
      criteria and had complementary heart explorations before surgery. There were 2
      deaths (3.4%) and 5 cases of cardiac morbidity (8.6%) in this group. CONCLUSION:
      The lack of any statistical difference between the two groups with and without
      risk criteria has led us to propose selective indications for preoperative
      explorations based on specific clinical criteria.

PMID- 8545365
TI  - [Syndrome of ovarian hyperstimulation. Report of a severe iatrogenic
      complication].
AB  - Severe ovarian hyperstimulation syndrome is a rare complication of ovulation
      induction with exogenous gonadotrophins. Severe forms involve acute renal
      failure, coagulation disorders, massive ascites, pleural effusion and may require
      pleural and peritoneal puncture. We report a case of severe ovarian
      hyperstimulation syndrome effectively treated by simple procedures in an
      intensive care unit.

PMID- 8545366
TI  - [Metastatic pulmonary carcinoma, revealed by Cushing syndrome, initially
      considered to have a pituitary origin. Course over 25 years].
AB  - It is often difficult to differentiate between Cushing's syndrome and ectopic
      ACTH hypersecretion which, in rare cases, may result from a carcinoid tumour.
      Several years may be required before development of patent Cushing's syndrome. We
      report the 25-year clinical course in a patient with a pulmonary carcinoid
      tumour. Initially, the hormone results led to the diagnosis of Cushing's syndrome
      and the patient was treated accordingly. Bilateral adrenectomy was performed in
      1969 followed by radiotherapy of the pituitary gland in 1975 for suspected
      Nelson's syndrome. Actually, the carcinoid tumour, located retrocardially, had
      gone unnoticed until 1989. Diagnosis was suspected during a hospitalization in
      our unit and the patient underwent tumour exeresis and left inferior lobectomy.
      Despite tumour removal and demonstration of tumoural ACTH secretion, the levels
      of ACTH and beta-lipotrope hormone remained high suggesting lymph node and/or
      pulmonary metastasis. This observation emphasizes the long clinical course of
      carcinoid tumours despite their malignancy and the unusual response to the
      dexamethasone test.

PMID- 8545367
TI  - [Introducing an implantable central venous catheter via the right pudendal vein].
AB  - Implantable central venous catheters are routinely introduced in the subclavian
      or jugular veins. In some cases such as thrombosis or infection, this
      localization must be avoided. In these circumstances, the inferior vena cava is
      used. The catheter can be inserted into the inferior vena cava via the right
      genital vein. Surgery is performed under general or loco-regional anesthesia. The
      right genital vein is approached using a MacBurney incision. The retroperitoneum
      is entered and the right genital vein is cannulated. The catheter tip is placed
      at the limit between the inferior vena cava and the right atrium. The port is
      placed in a subcutaneous pocket in the lower part of the thorax. In cases where
      the right genital vein is too narrow to allow catheterization, it is easy to
      proceed through the same incision and puncture the inferior vena cava.

PMID- 8545368
TI  - [Cancers of the skin, relations to ultraviolet rays].
AB  - There are three main types of skin cancers: basal cell carcinoma, squamous cell
      carcinoma and melanoma. They are very different in terms of clinical
      presentation, evolution, and prognosis. Their frequency is increasing and there
      is sufficient evidence for the aetiological role of solar ultraviolet radiation
      (UVR). This evidence is based largely on epidemiological studies, animal models
      and studies of xeroderma pigmentosum patients. The risk of squamous and basal
      cell carcinoma increases with chronic solar exposure while the risk of melanoma
      seems to be more influenced by intermittent exposures. The physiopathological
      mechanisms of UV carcinogenesis are not yet entirely understood. One of the main
      factors seems to be mutagenesis due to impaired DNA photoproducts repair.
      Alteration in immune function and genesis of free radicals induced by exposure to
      UVR may also play a central role in UV carcinogenesis.

PMID- 8545369
TI  - [Management of patients with simple cervical distortions].
AB  - Common distortion of the cervical spine without evidence of neurological or
      osteoligamentary damage is a frequent consequence of indirect head and neck
      trauma. The mechanism of the injury (called "whiplash", "coup de lapin", or
      "Schleudertrauma") does not imply direct trauma to the head or neck. In the acute
      phase, common distortion of the cervical spine requires treatment. Rapid
      management may avoid or considerably reduce the chronic pain syndrome with the
      characteristic chronic tension-like headache. The chronic pain and the numerous
      associated functional disorders are not well understood: certain factors favour
      central and peripheral dysfunction and others emphasize the importance of extra
      trauma phenomena. In our opinion, extra-trauma phenomena would explain the
      invalidating nature of pain in a small number of patients. Management of these
      chronic patients requires a multidisciplinary approach aimed at helping the
      patient overcome the inconveniences of this condition.

PMID- 8545370
TI  - [Hemorrhagic risk from antivitamins K: importance of the surveillance and
      information of patients].

PMID- 8545371
TI  - [Spontaneous pneumothorax disclosing pulmonary sarcoidosis].

PMID- 8545372
TI  - [Thiocyanate poisoning: a cause of false hyperchloremia].

PMID- 8545373
TI  - [Uncommon courses of mediastinal-pulmonary sarcoidosis].

PMID- 8545374
TI  - [Absence of regular medical follow-up: main cause of pneumocystosis diagnosed in
      patients with HIV infection in France in 1992].

PMID- 8545375
TI  - [Detection of Borrelia burgdorferi DNA by gene amplification in the muscle of a
      patient with fibromyalgia].

PMID- 8545376
TI  - [Bacterial esophagitis in AIDS].

PMID- 8545377
TI  - [Drug hypersensitivity syndrome during treatment with valproic acid].

PMID- 8545378
TI  - [Longitudinal fracture of the tibia caused by a minor injury].

PMID- 8545379
TI  - [Spontaneous unilateral adrenal gland hematoma in the postpartum period].

PMID- 8545380
TI  - [Lithiasis of the common bile duct and its treatment].
AB  - Controversy concerning the most appropriate treatment for a patient with a stone
      in the main duct almost always leads to an overused conclusion in medical
      surgical meeting--laparoscopic and classical surgery are complementary procedures
      -yet in everyday practice, the gastroenterologist will almost always order a
      retrograde cholangiogram to confirm the diagnosis and, once the obstacle
      identified, complete the procedure with an endoscopic sphincterotomy even though
      many surgeons emphasize its danger. At present few operators are equally
      experienced in the three major therapeutic options, endoscopy, conventional
      surgery and laparoscopic surgery, and consequently everybody has a tendency to
      favour his most proficient technique. Whatever technique is chosen, the aim is to
      completely remove all gall stones from the main bile duct with a minimum amount
      of risk and at the most reasonable cost. Careful attention to these three factors
      should help in weighting the advantages and disadvantages of the different means
      of management.

PMID- 8545382
TI  - [Treatment of rheumatoid psoriasis with bromocriptine].
AB  - Non-steroid anti-inflammatory drugs and/or gold salts were unsuccessful alone in
      providing symptom relief in three men with rheumatoid psoriasis. All three were
      treated with bromocriptine (5 mg/d in 2 doses) after verification of normal
      baseline and protirelin-stimulation prolactin levels. There was a beneficial
      effect in nocturnal pain relief, morning stiffness, the Lee and Ritchie scores
      and biological markers of inflammation. Two of the patients were able to return
      to regular work occupation after 15 and 45 days. In the third patient,
      bromocriptine was discontinued due to nausea and dizziness but was reintroduced
      successfully in fractionated doses after recurrence of the symptomatology.
      Treatment was continued without secondary adverse effects for 3 to 9 months
      providing continued symptom relief. Bromocriptine can be an effective adjuvant
      for the management of rheumatoid psoriasis.

PMID- 8545381
TI  - [Study of blood lead levels in a population of 616 subjects from the regions:
      Centre and Pays de Loire].
AB  - OBJECTIVES: Low-lead level exposure has been associated with harmful health
      effects. Blood lead is the most widely used marker of exposure. In this work, our
      purpose was to evaluate the present level of blood lead in a group of 616
      subjects from the general population living in two regions of France: Centre and
      Pays de Loire. METHODS: Subjects were randomly included in the study. Blood lead
      was measured by inductively coupled plasma mass spectrometry which is the most
      sensitive and specific method. RESULTS: The mean blood lead concentration of the
      population studied ranged from 46.7 +/- 20.5 micrograms/l in the 6-10 year old to
      86.6 +/- 42.4 micrograms/l in the 50-66 year old subjects. From 385 children
      under 13 years old, 5 had blood lead higher than 100 micrograms/l, the maximum
      acceptable level recommended by the American Centers for Disease Control. Women
      had lower blood lead values than men and their levels remained unchanged until 50
      years but increased beyond this age. CONCLUSION: Mean lead levels were low in
      this French population. There is however risk of higher levels in persons living
      in old housing.

PMID- 8545383
TI  - [Anti-thyroid autoantibodies in hepatitis C. Thyroid function after interferon
      therapy in 4 patients].
AB  - Four female patients had chronic hepatitis C associated with antithyroid
      autoantibodies. Hepatitis C virus infection was evidenced by liver biopsy and a
      positive-four-antigen recombinant immunoblot assay. All four patients were
      euthyroid before interferon therapy. Recombinant interferon alpha was given at a
      dose of 3 millions units three times a week for 6 months. At the end of the
      treatment, serum aminotransferase levels were within the normal range. Two
      patients progressed to hypothyroidism and 2 patients remained euthyroid. One year
      after the end of the treatment, only one patient had hypothyroidism and another
      had normal serum aminotransferase levels. These case-reports suggest that
      interferon administration may induce thyroid dysfunction in patients with
      antithyroid autoantibodies at the beginning of treatment. Thyroid dysfunction may
      be reversed when cytokine is withdrawn.

PMID- 8545384
TI  - [Angioplasty and coronary restoration using the internal mammary artery].
AB  - A technique of coronary surgical angioplasty is described. At the level of the
      stenosis the arteriotomy of the coronary artery is closed with the internal
      thoracic artery giving an enlargement patch effect. The major surface of the
      atherome plaque is excluded from the lumen of the anastomosis and put outside the
      suture line. The origins of the collateral arteries are kept in the vascular
      lumel. So the new remodeled coronary artery is formed with a small gutter of
      native coronary artery and the whole surface of the internal thoracic artery
      wall. In some cases it is useful to associate a limited endarterectomy to the
      angioplasty. Sixty-six surgical angioplasties have been done in extensive
      coronary disease. Operative mortality was 5.4% and myocardial infarction 5.4%.

PMID- 8545385
TI  - [Immunologic tolerance of fetal allograft].
AB  - In mammals, reproduction involves two potentially incompatible mechanisms:
      viviparity and development of a competent immune system. Thus the maternal and
      foetal organisms must respond by developing immunologic tolerance. The phenomenon
      does not involve total immunosuppression, but includes several highly precise
      processes initiated at conception. It is known that cell- and humour-mediated
      processes occur but their relative importance remains to be elucidated.
      Cytokines, especially those mediating T-helper2 cell response appear to play a
      predominant role in inducing immunologic tolerance to the foetal allograft. A
      better understanding of these mechanisms could have major implications in the
      diagnosis and treatment of repeated miscarriage and unexplained infertility.

PMID- 8545386
TI  - [Uterine malformations. Diagnosis, prognosis and treatment].
AB  - Malformations of the uterus result from a variety of anomalies during
      embryogenesis from the 6th to the 17th week of development. Agenesia (not
      discussed here) should be distinguished from unicornis, pseudo-unicornis,
      bicornis, bipartitus and communicating uteri (Musset's classification). Such
      malformations occur in 3 to 4% of all women. Sonography provides the most useful
      information for diagnosis and should be used as first intention examination
      together with a work-up to determine extension. In certain cases, hysterography
      and laparoscopy may be required. Sterility is not increased in women with a
      malformation of the uterus, but fecundity is reduced due to a high rate of
      spontaneous abortions (30 to 40%) and premature births (15 to 45%). Obstetrical
      prognosis in case of a partitioned uterus can be improved by hysteroscopic
      resection of the partition. Most authors propose endoscopic treatment when a
      malformation of the uterus is diagnosed during a sterility work-up.

PMID- 8545387
TI  - [Pseudo-cholangitis, a form of erythromycin-induced hepatitis].

PMID- 8545388
TI  - [Spontaneous rupture of an implantable venous catheter].

PMID- 8545389
TI  - [Encephalopathy in cat scratch disease].

PMID- 8545390
TI  - [Neuromyopathy after administration of succinylcholine].

PMID- 8545391
TI  - [Atrium 300 hepatitis. A new case].

PMID- 8545392
TI  - [Interaction between prostaglandin E and oral anticoagulants].

PMID- 8545393
TI  - [Recurrent epididymitis, associated with Behcet disease, in an indigenous patient
      in France].

PMID- 8545394
TI  - [Visceral leishmaniasis and human immunodeficiency virus (HIV) infection in the
      south of France].

PMID- 8545395
TI  - [Gene therapy. A new prospect in the treatment of liver tumors].
AB  - To be effective, gene therapy requires three essential elements: a gene to
      transfer, a vector to carry the gene,and a target cell (here the cancer cell).
      One type of gene action of particular interest is the suicide gene. When
      introduced into the cell, the expression of this gene leads to cell death by
      production of pro-drugs. For example the gene for thymidine kinase from the type
      1 herpes simplex virus (HSV1-TK) transforms nucleoside analogues such as
      ganciclovir into triphosphates which inhibit polymerases. When incorporated into
      deoxyribonucleic acid during cell division, DNA synthesis is arrested causing
      cell death. Thus only cells containing the HSV1-TK gene are sensitive to
      ganciclovir. The most widely used vectors are retroviruses. When these vectors
      infect a cell, the genes they carry are incorporated into the cell genome and, in
      the case of suicide genes, lead to cell death. These retrovirus vectors must
      however be transformed by genetic engineering to remove their capacity for
      replication so that no viral replication occurs, limiting the effect to the
      infected cell alone. In cancer therapy, retrovirus appears to be a choice vector
      since only cells undergoing active division, such as malignant tumour cells, are
      affected by the gene transfer. Primary or secondary liver tumours are a choice
      target for gene therapy for several reasons. First, cell division in these
      tumours is permanent and rapid while the surrounding healthy tissue is in a
      quiescent state. Secondly, gene therapy could be possible in man since extra
      hepatic diffusion of the retrovirus could be avoided by temporary exclusion of
      the hepatic circulation during perfusion of the retrovirus. Although the long
      term risks of using retrovirus vectors for gene therapy (effect on germ cells,
      oncogenesis), the effect on multiple or large tumours of the liver and the
      proliferative potential of residual tumour cells remain to be determined, gene
      therapy for liver cancer is now entering the stage where promising clinical
      applications may soon be proposed. We have applied gene therapy in in vivo
      experimental animal models with promising results suggesting that liver cancer
      may be one of the first applications of this new therapeutic tool in man.

PMID- 8545396
TI  - [Blastocystis hominis: a common commensal in the colon. Study of prevalence in
      different populations of Paris].
AB  - OBJECTIVES: To compare the prevalence of Blastocystis hominis in different
      population categories in Paris, including immunodepressed subjects. METHODS:
      Stool examinations were performed for 7,677 patients to determine the prevalence
      of Blastocystis hominis. RESULTS: Prevalence varied according to the population
      group: subjects free of any digestive tract disorders 17.4%; adults with
      digestive tract disorders 19.8% (this level was independent of digestive tract
      motility and of ethnic origin); children 13.8% (p < 0.01). In HIV-positive
      patients, the prevalence in immunocompetent patients was 19.6% compared with 15
      to 16% in patients with AIDS (difference non significant). Blastocystis hominis
      was shown to be non-contagious in children and was not found to be sexually
      transmitted in homosexual men. CONCLUSION: Generally, Blastocystis hominis
      infection resolves spontaneous before any manifestation of the protozoa. This
      common parasite is a commensal germ of the intestinal tract, even in subjects
      free of gastro-intestinal manifestations, and does not usually require
      prescription of an antibiotic. In exceptional cases with rapid proliferation,
      treatment can be proposed with nitroimidazol, particularly for certain strains
      with an abnormal variability.

PMID- 8545397
TI  - [Intravascular malignant lymphoma (ex-malignant angioendotheliosis). 3 cases].
AB  - Malignant angioendotheliomatosis is an intravascular proliferation of tumour
      cells in the small arteries, veins and capillaries. Its lymphomatous origin has
      been proved recently by immunohistochemistry. It is a rare, generally rapidly
      fatal condition. Less than 150 cases have been reported in the literature. We
      report three cases. Long course fever with delayed neurologic disturbances were
      observed in the first case and long course fever, hyponatraemia, corticotropic
      and gonadotropic insufficiency in the second. The third case began with febrile
      meningo-encephalitis. Diagnosis was made at autopsy in the two first cases and on
      evidence from kidney needle-biopsy in the third. Clinical manifestations are
      polymorphic and frequently simulate vasculitis. Neurologic signs are the most
      common. Histologically, kidneys, skin, endocrine glands, lungs, muscles and most
      of the organs may be involved. Surprisingly lymph nodes, bone marrow and spleen
      are often free from disease. Current treatment is based on polychemotherapy.
      Earlier diagnosis of the disease should improve the prognosis as observed in our
      third patient.

PMID- 8545398
TI  - [Expansive uterine myoma during tamoxifen therapy. 11 cases].
AB  - Tamoxifen, a non-steroid anti-oestrogen derivative of diethylstilboestrol, is the
      main drug used for hormone therapy for hormone-dependent breast cancer. This
      ambivalent drug has both antagonist and agonist effects. While tamoxifen blocks
      tumour growth it can also have an undesirable agonist effect on the genital
      tract. The uterus is a target organ for this paradoxical action due to
      proestrogenic stimulation of the endometrium and the myometrium. We observed
      eleven cases of uterine fibromyoma during treatment with tamoxifen which required
      hysterectomy due to increased tumour volume. The pathology report on the surgical
      specimens did not show any evidence of malignancy. Differential diagnosis is
      based on sarcomatous degeneration of the fibromyoma and presence of intra
      myomatous metastases from the breast. Hysterectomy is indicated in menopaused
      patients with a symptomatic fibromyomatous uterus before starting long-term anti
      oestrogen therapy for hormone-dependent breast cancer.

PMID- 8545399
TI  - [Prostate specific antigen. Clinical applications of ultrasensitive assay].
AB  - Recent progress in the techniques used to assay prostate specific antigen (PSA)
      have made this diagnostic tool even more useful in the management of patients
      with cancer of the prostate. However, although "ultrasensitive" methods can now
      detect minute levels, there still is no widely accepted definition of the
      detection threshold making it difficult to compare results reported with the
      different techniques. Ultrasensitive assay is particularly interesting in
      patients who have had radical prostatectomy, offering complementary information
      to the pathology examination of the surgical specimen. Used as a tool for
      following disease course after surgery, ultrasensitive PSA is currently the most
      sensitive measure of disease recurrence. Ultrasensitive assay can also give an
      evaluation of the effect of post-surgery complementary radiotherapy. Inversely,
      it adds no further information compared with regular assay before surgery. Thus,
      ultrasensitive assay is not indicated for differential diagnosis or screening
      programmes but is a valuable tool for evaluating the effectiveness of curative
      surgery or exclusive curative radiotherapy.

PMID- 8545400
TI  - [Relation between the parathyroid glands and arterial pressure: is there a
      parathyroid hypertensive factor?].
AB  - Parathyroid hypertensive factor (PHF) is a newly discovered circulating factor
      that has been implicated in some forms of hypertension. Such an involvement has
      been established in several animal models and in hypertensive patients. PHF
      originates from the parathyroid glands. This explains why hypertensive
      individuals often have high levels of circulating parathyroid hormone (PTH),
      which is itself hypotensive. This would reflect the activity of the parathyroid
      glands, which would produce PHF concomitantly with PTH. The mechanism of action
      of PHF involves an increase in calcium-channel activity in vascular smooth muscle
      cells. The opening of these channels would lead to increase calcium entry into
      these cells, resulting in increased sensitivity to other vasoconstrictors. PHF
      level explains why a high calcium diet may be effective in lowering blood
      pressure in patients who respond to calcium-channels blockers: dietary calcium
      might inhibit the production of PHF (and PTH), whereas calcium-channels blockers
      would inhibit PHF at its target site.

PMID- 8545402
TI  - [Spontaneous gastric rupture].

PMID- 8545401
TI  - [Photosensitization induced by quinine used in the treatment of idiopathic
      nocturnal cramps].

PMID- 8545403
TI  - [Conjunctival aphthosis, an unusual site in Behcet disease].

PMID- 8545404
TI  - [Drug excipients containing licorice: a cause of hypokalemia].

PMID- 8545405
TI  - [Polyarthritis during treatment with interferon-alpha. 2 cases].

PMID- 8545406
TI  - [Vasculitis and diabetes insipidus, reversible by administration of
      cyclophosphamide].

PMID- 8545407
TI  - [Carcinomatous linitis of the bladder. A new case].

PMID- 8545409
TI  - [Arterial hypertension in Blacks].

PMID- 8545408
TI  - [Toxic dermatitis caused by pyrimethamine in patients with acquired
      immunodeficiency virus infection].

PMID- 8545410
TI  - [Inhalation therapy for asthma in children. Questions about effectiveness].
AB  - A better understanding of childhood asthma, a disease affecting 6 to 10% of the
      paediatric population, has led to the development inhalation systems which can
      provide undeniably effective therapy but also raise a certain number of questions
      as to the quantity of drug actually reaching the pulmonary airways. When
      aerosols, the reference system, are used with a good inhalation technique, as
      much as 80% of the active product goes no further than the oral cavity, only 10%
      reaching the intrapulmonary airways. In addition, the system requires a co
      ordination between hand movements and inspiration which is beyond the capacity of
      children under 7 or 8 years of age. Doses and granulometric flow also vary
      greatly depending on the propulsion gas. Inhalation chambers mounted on face
      masks avoid the problem of co-ordinated movements, increasing pulmonary
      deposition, but real drug delivery in infants who breathe through the nose
      remains to be determined. Systems which deliver the drug in the form of a powder
      have also been developed. With these devices, the product is held in a chamber
      together with carrier particles and is inhaled as inspiration creates air
      turbulence in the chamber. Minimal inhalation peak is the limiting factor.
      Nebulizers offer another possibility since no voluntary control of respiration is
      required, the child breathes at his own rhythm. The drug is nebulized either by a
      forced air or ultrasound system. Such systems may be very useful for infants but
      are usually not adapted for toddlers or older children. Despite the lack of
      precision as to the quantity of drug actually delivered to the pulmonary airways,
      the use of inhalations has completely changed the quality of life of children
      with chronic asthma. Further progress will be made through a better understanding
      of the two most important factors: the child and corticosteroids. Indeed, the
      child's co-operation (or non-co-operation) is one of the major sources of
      (un)successful treatment: even the best inhalation system can have little impact
      on the disease if it is not accepted and used correctly by the child.

PMID- 8545411
TI  - [Celioscopy in the treatment of acute small bowel occlusions: preliminary
      results].
AB  - OBJECTIVE: The aim of this study was to determine the applicability and short
      term results as well as the indications for laparoscopic surgery in acute
      occlusion of the small bowel. METHODS: From May to September 1995, 9 consecutive
      patients (8 females, 1 male, mean age 54.4 years, range 27-82), hospitalized for
      acute occlusion of the small bowel were included in an evaluation of laparoscopic
      cure. Patients were divided into two groups according to the presence (n = 5) or
      absence (n = 4) of a past history of medial laparotomy. RESULTS: Laparoscopic
      surgery was used in all patients with no complications. In the group with a past
      history of laparotomy, the procedures were more difficult and the duration of the
      procedure was longer (220 +/- 74 min versus 104 +/- 11) (p < 0.01). The
      advantages of laparoscopic surgery were decreased post-operative pain and shorter
      duration of ileus and hospitalization. CONCLUSION: Laparoscopic treatment of
      acute occlusion of the bowel is possible. The procedure should probably be
      reserved for patient without a past history of medial laparotomy. A long-term
      study is required to assess the risk of recurrence.

PMID- 8545412
TI  - [Quantitative detection of pp65 intraleukocyte cytomegalic antigen in renal
      transplantation].
AB  - OBJECTIVE: To assess the clinical value of quantitative assay of leukocyte
      cytomegalovirus antigen (LCA) in the management of immunodepressed patients.
      METHODS: Thirty-three kidney transplant recipients followed a weekly follow-up
      protocol during the first 3 months after transplantation. LCA was compared with
      cytomegalovirus (CMV) detection in blood using fibroblast cell culture and with
      serology tests. LCA was expressed in number of positive cells per 2.10(5)
      leukocytes, detected by immunofluorescence with a specific monoclonal antibody
      directed against the pp65 antigen. The standard culture method and a rapid
      centrifuge method were used for blood samples. The serum level of anti CMV
      antibodies was determined by ELISA. RESULTS: CMV infection defined as positive
      viraemia and/or positive serology tests was diagnosed in 22 of the 33 patients.
      LCA was detected in 20 patients, including all those with clinical signs of
      infection. Serology was the only method giving a positive diagnosis in 2 patients
      and was negative in 3 infections positive for LCA. Viraemia was negative in 2
      patients positive for LCA. LCA was detected in 60 of the 65 blood samples with a
      positive viraemia test and in 46 of the 165 negative samples (sensitivity 92% and
      specificity 72%). Quantitatively, LCA in samples taken from patients with
      clinical signs was higher than that in samples taken from asymptomatic patients
      (51 +/- 5 versus 20 +/- 2, p < 0.001). In addition, LCA was detected a mean 7.6
      +/- 4 days before significant changes in serology tests, 2.2 +/- 1.6 days before
      the viraemia and 7.1 +/- 1 days before clinical manifestations. CONCLUSION:
      Leukocyte cytomegalovirus antigen gives a sensitive means of early positive
      diagnosis. The quantified level illustrates the patient's risk of infection. This
      new method is a very helpful tool in following renal transplantation recipients.

PMID- 8545413
TI  - [Multiple (visceral and neurologic) tumors].
AB  - OBJECTIVES: We studied the frequency, histology, epidemiological features and
      delay between tumours with one localization in the central nervous system. We
      searched for an association between neurological and visceral neoplasia and tried
      to establish a guideline when central nervous system tumours appear after a
      visceral tumour. METHODS: From January 1973 to December 1993, we archived all
      patients admitted for neurological tumours or who had tumours discovered in our
      ward. Both neurological and non-neurological and malignant and non-malignant
      tumours which appeared simultaneously or after a delay were recorded. We retained
      only patients who had one neurological and one or more visceral tumours (n = 11).
      Multiple neurological or visceral tumours and phacomatosis were excluded.
      RESULTS: The association between neurological and visceral tumours is an uncommon
      but not exceptional finding as multiple tumours were seen in 1% of the cases
      admitted during the study period with a neurological or a visceral tumour.
      Meningioma and glioma were the most frequent histological type of central nervous
      system tumours (10 cases out of 11). Malignant melanoma was particularly frequent
      among the systemic tumours (3 out of 13 tumours). The classical association
      between meningioma and malignant breast neoplasia was absent in our study but an
      association of malignant melanoma and tumours of the central nervous system was
      found in 3 patients. Age and sex were similar for neurological and visceral
      tumours. The delay separating the discovery of the two tumours was shorter when
      the first tumour was a neurological tumour. CONCLUSIONS: These findings
      demonstrate the frequency of associated neoplasia. We did not find the classical
      association between breast cancer and meningioma but did find one between
      malignant melanoma and tumours of the central nervous system. This short study
      emphasizes the usefulness of having histological proof (when possible) before
      considering a cerebral tumour as a metastasis of a visceral tumour.

PMID- 8545414
TI  - [Selective endoscopic sympathectomy for palmar hyperhidrosis].
AB  - OBJECTIVES: Thoracic sympathectomy is the radical and usually definite treatment
      of palmar hyperhidrosis. Improvement of surgical endoscopy techniques makes it
      possible to perform the procedure through thoracoscopy, thus minimizing operative
      trauma and sequellae. However, thoracic sympathectomies give rise to a high rate
      of compensatory sweating which is the most important adverse effect of the
      technique. METHODS: We developed a technique of selective sympathectomy which
      only divides the rami communicanti from the first to the fourth thoracic
      ganglion. We performed 90 thoracic sympathectomies in 46 patients. They were
      performed in a truncal manner in 32 patients while it was selective in the last
      14 patients. RESULTS: The success rate was 97.5% (2 failures). After reoperation
      of these 2 failures, the success rate was 100%. The global rate of compensatory
      sweating was 47.5%. In the 14 last patients who underwent a selective
      sympathectomy, only one complained of compensatory sweating. CONCLUSION:
      Endoscopic sympathectomy is an effective means of treating palmar hyperhidrosis.
      Rigorous technique should help reduce the risk of compensatory sweating.

PMID- 8545415
TI  - [Extracorporeal lithotripsy in the treatment of upper urinary tract lithiasis].
AB  - The advent of extra-corporal shock-wave lithotripsy in the eighties totally
      changed management strategies for renal and ureteral lithiasis of the upper
      urinary tract. Currently, approximately 80% of all patients can benefit from
      lithotripsy with an overall success rate of about 75%. Although classical surgery
      has a higher success rate of about 90%, extra-corporal shock-wave lithotripsy has
      many advantages. First there is a very low risk of morbidity (pain,
      immobilization, complications) for this outpatient treatment. Second, the overall
      cost, including that of preventive treatment, is low as illustrated by the major
      reduction in the number of cases of pyonephritis on stones and of corraliform
      lithiasis. The apparent safety of shock-wave therapy should not mask the risk of
      unacceptable indications: small stones which may resolve spontaneously or
      inversely very large stones carrying the risk of residual fragments and renal
      damage. Long-term morbidity remains to be evaluated, but the management of upper
      urinary tract lithiasis now relies heavily on shock-wave therapy alongside
      conventional surgery and percutaneous or endoscopic methods.

PMID- 8545416
TI  - [Effects of amiodarone on thyroid function].
AB  - Amiodarone has been used in cardiology for more than 20 years as an anti-angina
      and anti-arrhythmia agent. In the seventies, variations in thyroid hormone and
      TSH concentrations were described in treated patients. Only recently, however the
      pathogenic mechanisms leading to dysthyroidism in long-term treatment have been
      described. Today, the gravity of amiodarone-induced hyperthyroidism has been
      greatly reduced due to a better understanding of the underlying mechanisms and
      better surveillance of thyroid function. In clinical practice, the following
      attitude can be proposed. Thyroid exploration should be completed before
      prescribing amiodarone: clinical examination should emphasize personal or
      familial history in search of dysthyroidism or goitre; hormone assays (TSH, free
      T4) are needed to eliminate any latent thyroid dysfunction, particularly
      hyperthyroidism with little or no clinical manifestation but sometimes the causal
      factor in cardiac symptomatology; search for a significant level of anti
      thyroperoxidase antibodies can reveal underlying chronic thyroiditis. After
      prescription, clinical surveillance and TSH assay should be performed at 3 months
      then every 6 months during treatment. After withdrawal, surveillance should be
      continued with check-ups at 6 and 12 months.

PMID- 8545417
TI  - [Idiopathic CD4 lymphocytopenia syndrome disclosed by meningeal cryptococcosis. A
      new case].

PMID- 8545418
TI  - [Neuro-perineal disorders in hemi-syndromes of the cauda equina. 30 cases].

PMID- 8545419
TI  - [Jarisch-Herxheimer reaction in leptospirosis].

PMID- 8545420
TI  - [Pericardial perforation caused by an osteogenic exostosis].

PMID- 8545422
TI  - [Hyperkalemia induced by high-dose trimethoprim].

PMID- 8545421
TI  - [Arterial embolization: a new treatment of menorrhagia in uterine fibroma].

PMID- 8545423
TI  - [Important chemosensitivity of extraneural metastases of oligodendroglioma].

PMID- 8545424
TI  - [Tissue calcifications in a dialyzed female patient. Role of hypervitaminosis K].

PMID- 8545425
TI  - [Prognosis of tuberculous acute respiratory distress syndrome].

PMID- 8545426
TI  - [Atherogenicity of low-density lipoproteins (LDL). A problem of quantity or
      quality?].
AB  - The relationship between elevated plasmatic LDL and increased risk of coronary
      artery disease is definitively established. However the qualitative aspect of the
      particles also appear to play a significant role: a structural heterogeneity
      within the LDL particles themselves has been recognized for a number of years.
      Multiple subclasses have been characterized in several populations of normal and
      hyperlipidaemic subjects. Some of these subclasses are linked with an atherogenic
      potential, this is the case for the smaller and the more dense of the particles,
      defined as the phenotype B. Epidemiological studies have consistently shown an
      association of this phenotype with an increased risk of coronary artery disease,
      and various reports have linked it with clinical and angiographic indices of the
      disease. However, these studies do not allow for causality, and after adjustment
      for the plasma TG level LDL subclasses distribution is not an independent
      predictor of coronaropathy anymore. The underlying mechanisms leading to the
      association are not yet established, but it is possible that small dense LDL are
      per se atherogenic. Considerable evidence is now available to support some of the
      hypothesis: denser LDL have a lower affinity for the LDL BE receptor, are more
      succeptible to oxidative damage, and may have modified interaction with various
      components of the arterial wall. Moreover several authors have shown that a
      number of lipid lowering drugs, like fibrates, could normalize to a significant
      extent the plasma profile of LDL as a result of preferential reduction in the
      elevated levels of the denser more atherogenic subspecies.

PMID- 8545427
TI  - [New antithrombotic agents].
AB  - The wide range of compounds currently being developed is the result of the
      continuing need for validated new antithrombotic agents. The prevention and
      treatment of venous thrombosis is predominated by anticoagulants: low molecular
      weight heparins, and potentially new antithrombin agents including hirudin. The
      effectiveness of new antiplatelet agents, and particularly c7E3 and integrelin,
      confirms the hypothesis concerning the role played by platelets in thrombogenesis
      in coronary arteries. But, due to the proaggregating effect of thrombin,
      anticoagulants could also have an important role in preventing arterial clots,
      either when given alone or in combination. Finally, the development of
      antithrombin and anti-platelet-glycoprotein IIb IIIa given orally is one of the
      major objectives of current research. Until the ideal antithrombotic agent is
      discovered, multiple-drug regimens combining anticoagulants and/or antiplatelet
      agents could be proposed in patients with a very high risk of thrombosis. Such
      regimens must taken into account the increased risk of bleeding and be adapted on
      the basis of careful laboratory surveillance.

PMID- 8545428
TI  - [Unstable angina. Physiopathology, clinical course and therapeutic principles].
AB  - The pathogenic mechanism of unstable angina, a clinical expression of coronary
      heart disease, is similar to that of myocardial infarction. The main event is the
      instability of the atheromatous plaque adhering to the coronary intima leading to
      thrombosis and occlusion. Clinical manifestations can be severe since fatal or
      non-fatal myocardial infarction occurs in 3.9% and 5.4% of the case respectively.
      Adapted medical treatment can stabilize the situation in most patients,
      justifying early preventive treatment. Moreover, it has been estimated that a
      premonitory phase of angina had gone unnoticed or undiagnosed in one-half of all
      myocardial infarcts. In nearly all patients with unstable angina, coronarography
      is of major importance for rapidly defining an adapted therapeutic strategy.
      Myocardial revascularization (especially by angioplasty) is often needed to limit
      the risk of major cardiac events occurring within a short or moderate delay.
      Unfortunately, these procedures carry a supplementary risk of thrombosis. Thus
      the emphasis placed on measures capable of improving the anti-thrombotic risk in
      unstable angina by using new antiplatelet agents, or for certain patients at high
      risk of a major cardiac event, antithrombosis agents. Finally, the search for
      compounds capable of stabilizing the previously formed atheromatous plaque (and
      thus avoiding rupture) is a prime objective for an overall management strategy
      for patients with coronary heart disease.

PMID- 8545429
TI  - [Post-infarction myocardial viability. Role of scintigraphic evaluation].
AB  - Myocardial scintigraphy is clinically relevant in the management of patients with
      previous myocardial infarction. The purpose of such investigation is first to
      quantify the infarcted area, secondly to detect and quantify a residual
      myocardial ischaemia and thirdly to evidence the presence of chronically
      hypoperfused and akinetic but potentially viable myocardium (hibernating
      myocardium). Thallium SPECT is to be preferred in this indication even if new
      tracers could be promising: fatty acids, 18Fluorodesoxyglucose imaged by PET or
      SPECT cameras. In such indications, stress tests should sometimes be completed
      with delayed or rest acquisitions. In case of negative stress and rest thallium
      SPECT, PET scans may be useful in patients with large myocardial infarction,
      severe left ventricular dysfunction, segmental wall motion asynergy, and absence
      of previously demonstrated residual ischaemia in order to select patients
      eligible for coronary revascularization or heart transplantation.

PMID- 8545431
TI  - [Exercise capacity after heart transplantation].
AB  - Independently of phenomena related to rejection, atherosclerosis of the grafted
      heart or high blood pressure, there exists a qualitative and quantitative
      degradation of response to exercise in heart transplant recipients. Maximal
      oxygen consumption is generally reduced to 40 to 60% of normal levels. There are
      several interactive mechanisms. Paradoxically, the transplanted heart is a clear
      demonstration of the fact that several other elements are involved in the
      organisms response to exercise. Indeed, ventilation, exercise load, peripheral
      circulation, muscle metabolism and neurohormonal response also play a role.
      Vasoactivity of the peripheral arteries limits distribution and extraction of
      oxygen during exercise. Noradrenaline, renin, atrial natriuretic factor,
      vasopressin and endothelin levels are normal at rest, but an overreaction occurs
      during exercise. The percentage of type I (oxidative) fibres is reduced in
      muscles. Cyclosporine has also been shown to have a toxic effect on mitochondria
      in muscles. The deinnervated transplanted heart is thus called upon to work in
      coordination with peripheral elements which have also undergone alterations.
      Consequently, response to exercise cannot be significantly increased above the
      level reached before transplantation. Usually patients are not greatly hindered
      in their daily activities and rarely complain of breathlessness. Nevertheless, an
      improvement would be appreciated. A coherent physical rehabilitation programme
      can increase maximal oxygen consumption by 25 to 30% in these patients,
      essentially via improvement in peripheral anomalies. It is more difficult to
      modify cardiac response.

PMID- 8545430
TI  - [Stress ultrasonography with dobutamine in the diagnosis of coronary disease].
AB  - Digital stress echocardiography (DSE) with dobutamine infusion has recently
      emerged as an attractive alternative to exercise stress testing for evaluating
      coronary artery disease. DSE seems particularly useful in the diagnosis or the
      assessment of ischemia in patients unable to exercise or when the test is
      difficult to interpret. DSE has also proved to be useful in patients undergoing
      preoperative evaluation of cardiac risk. The assessment of residual myocardial
      viability in patients with previous myocardial infarction is another promising
      development. After a description of the methodology of dobutamine stress
      echocardiography, this article reviews the experience obtained to date with this
      technique in the diagnosis and the evaluation of coronary artery disease.

PMID- 8545432
TI  - [Osteo-articular complications of heart transplantation].
AB  - Heart transplantation is an effective means of treating irreversible heart
      failure in selected patients. Preventing organ rejection requires
      immunosuppressor treatment with corticosteroids, azathioprine and/or
      cyclosporine. Bone and joint complications are frequent and increase overall
      morbidity directly related to anti-rejection therapy. Corticosteroids favour
      osteopenia which can be detected by measurement of bone density. The risks
      include spontaneous wedge fractures of the spine and aseptic necrosis. The
      frequency of complications has been reduced with the use of cyclosporine allowing
      a reduction in corticosteroids. Raised serum urate levels and increased risk of
      gout can be induced by cyclosporine. The gout in these patients has a particular
      course since it appears rapidly after only a few months of hyperuricaemia.
      Several joints may be involved with production of tophi. Treatment is
      particularly difficult. Its frequency increases after heart transplantation
      compared with other organs which can be explained by the more prevalent
      prescription of diuretics which further aggravate urate secretion. These
      complications cause further discomfort in transplant recipients.

PMID- 8545433
TI  - [Arterial coronary bypass].
AB  - The long-term patency of internal mammary artery grafts used for myocardial
      revascularization bypass surgery is the main reason arterial grafts have largely
      replaced saphenous vein grafts. Indeed after 10 years, venous grafts often
      occlude or develop major atheromatous wall lesions. Use of an internal mammary
      artery graft for myocardial revascularization on the anterior interventricular
      coronary artery has thus greatly improved the beneficial effect of coronary
      bypass surgery. Several surgical teams have attempted to further improve results
      by using two internal mammary arteries or even other arterial grafts. This
      evolution towards "arterial coronary surgery" have nevertheless been criticized
      by some due lower than expected permeability rates and increased post-operative
      morbidity. Most surgical teams in France have thus maintained their preference
      for single internal mammary grafts and several saphenous vein grafts. Unlike
      these teams, we believe that the use of two internal mammary grafts together with
      other arterial grafts does not increase surgical risk and provides better quality
      long-term myocardial revascularization than do conventional procedures. It is
      important however to select patients for arterial surgery among those with a good
      general health status susceptible of benefiting from the long-term permeability
      of mammary artery grafts.

PMID- 8545434
TI  - [Reduction of atrial fibrillation. New concepts, new strategies].
AB  - Restoring sinus rhythm is patients with non-valvular atrial fibrillation has two
      objectives: restore haemodynamic performance and reduce the risk of
      thromboembolism. Whether the cardioversion is spontaneous or induced with drugs
      or electroshock, the process itself carries the risk of systemic embolism
      attributed to the transitory inactivity of the left atrium. Current practice of
      giving anticoagulants at least 4 weeks before electric cardioversion is a
      compromise between the embolic risk of cardioversion estimated at 0.4 to 0.8% and
      haemorrhagic complications related to low blood coagulability estimated at about
      1% per year. The advent of transoesophageal echography has made it possible to
      study the atrium in detail in search of thrombi. The result has been a revolution
      in our concepts and therapeutic approach to atrial fibrillation and
      cardioversion. Recent studies have shown that "rapid cardioversion" associated
      with minimal 48-hour anticoagulation with heparin IV and transoesophageal
      echography to eliminate a thrombus in the atrium and/or the atrial appendage can
      be proposed without increasing the risk of embolism. Besides simplifying the
      therapeutic protocols (but at the cost of the semiinvasive nature of the
      transoesophageal echocardiography), this method also has the merit of restoring
      atrial function rapidly, particularly in cases of recent onset arrhythmia.

PMID- 8545435
TI  - [Restenosis after angioplasty. Diagnosis and treatment].
AB  - Restenosis is the main limitation of percutaneous transluminal coronary
      angioplasty (PTCA). It occurs exclusively within the first 6 months after
      successful PTCA and leads in 25 to 30% of the cases to repeat revascularization.
      Its pathophysiology appears to involve mainly intimal hyperplasia at the injury
      site and constrictive remodeling of the whole artery; the relative roles of each
      remain debated. Detection of restenosis is often simple, when typical angina
      recurs after a symptom-free interval, but is often enhanced by a stress test,
      sometimes coupled to a thallium scintigraphy. The value of these tests is
      enhanced when a pre-PTCA test is available for comparison. The only preventive
      treatment with proven efficacy is the placement of stents, which however do not
      provide full protection against the development of restenosis, which suggests
      that ideal prevention should combine a mechanical approach, targeted against
      vessel remodeling and a biological approach targeted against intimal hyperplasia.

PMID- 8545436
TI  - [Is coronary angioplasty the best treatment of acute myocardial infarction?].
AB  - Although the efficacy and simplicity of intravenous thrombolysis makes it the
      gold-standard for the treatment of acute myocardial infarction, coronary
      angioplasty remains a valuable alternative. Thrombolysis has the disadvantage of
      increasing the risk of haemorrhage and is contraindicated in many cases. In
      addition, thrombolysis appears to have little effect on prognosis in patients
      with an infarction complicated by cardiogenic shock or those with an occlusion of
      the venous graft. Finally, when the electrocardiographic findings are not patent,
      the benefit/risk ratio may be uncertain. Many patients with an acute myocardial
      infarction are thus totally excluded from thrombolysis making this required
      selection the main limitation of the treatment. In all these situations, the only
      effective treatment is primary or direct coronary angioplasty. Major series of
      patients treated with primary angioplasty have shown that the treatment can be
      effective on coronary permeability, preservation of ventricular function and
      short and long-term survival. Several other comparative and randomized studies
      have confirmed that coronary angioplasty can be an effective alternative, in
      particular in high-risk patients (elderly subjects, anterior infarctions, women).
      Finally, the economic data available tend to show that costs for angioplasty are
      lower than the costs of thrombolysis due to the reduction of hospitalization time
      and number of readmissions. In conclusion, coronary angioplasty is certainly the
      best treatment for acute myocardial infarction, at least for the most severe
      cases and often the only possible option for those with a contraindication for
      thrombolysis. Operational requirements mean that cardiology emergency facilities
      will have to be adapted to provide coronary angioplasty 24 hours a day in
      experienced interventional centres. At the present time, well-managed pre
      hospital screening to identify patients with an indication for coronary
      angioplasty should allow emergency transportation to currently operating centres.

PMID- 8545437
TI  - [Atrial natriuretic factor and brain natriuretic peptide. Variations in elderly
      subjects with heart failure].
AB  - Atrial natriuretic factor (ANF) is a peptide hormone secreted by the atria in
      response to increased transmural pressure. This peptide is the first of a series
      of natriuretic hormones which also includes brain natriuretic peptide (BNP). It
      is destroyed mainly by an ubiquitous enzyme, neutral endopeptidase (NEP). Its
      main actions are vasodilatation and natriuresis. It is the main physiological
      agonist of the renin/angiotensin/aldosterone system. In elderly subjects free of
      cardiovascular disease, baseline concentrations are higher than in younger
      subjects. In patients with congestive heart disease (CHD), the level of ANF rises
      due to permanent increased filling pressures. Both atrial and ventricular
      secretion increase ANF levels which loose their day/night rhythm. ANF is a risk
      factor independent of mortality, rhythm disorders and acute heart failure in
      patients with heart failure. BNP is also raised in CHD. There is an inverse
      correlation between concentration and severity of left ventricule dysfunction.
      There has been little work on ANF in elderly subjects with CHD. ANF is elevated
      in these patients and is an independent risk factor for cardiac decompensation.
      In addition, in very elderly subjects where the diagnosis of CHD is difficult and
      echocardiography not always possible, assay of BNP could be an interesting
      diagnostic tool. Currently work on therapeutic possibilities (administration of
      exogenous ANF, combinations with NEP inhibitor/conversion enzyme inhibitor,
      ANF/diuretics) have revealed certain problems (short half life of ANF, transient
      effects, non-specific activity of NEP). The usefulness of ANF and BNP in heart
      failure in elderly subjects will undoubtedly lie in its capacity to mark disease
      severity and as a diagnostic tool, particularly in case of acute dyspnoea.

PMID- 8545438
TI  - [Ambulatory measurement of blood pressure].
AB  - The advent of new techniques has greatly contributed to the development of
      ambulatory measurement as a noninvasive method for evaluating blood pressure. The
      technique implies use of a validated and reliable standardized apparatus. The
      operator must strictly comply with operating procedures, which must also be
      explained to the patient. Ambulatory measurement can be meaningful only if the
      results are compatible with reference values, which have now been established,
      and if the causes of possible error can be recognized and interpreted. Ambulatory
      blood pressure measurement has greatly improved our knowledge of physiological
      and pathological variations over the circadian cycle including day/night
      variability and the effects of psychosensorial stimulation. Diagnostic
      indications are clearly identified and include borderline hypertension suspected
      but not identified after about 3 months, the white coat effect, severe
      hypertension when modifications in the circadian cycle are suspected, paroxysmal
      hypertension, suspected pheochromocytoma, and gravid hypertension or an inversion
      of the circadian cycle possibly preceding an episode of eclampsia. There are also
      a certain number of particular indications in patients with degenerative or
      primary conditions affecting their autonomy. The true prognostic value of these
      recordings was recognized several years ago and has been confirmed by clinical
      trials. For example, the white blouse effect has no significant implication in
      terms or predicting less favourable morbidity or mortality. Finally, ambulatory
      blood pressure measurement has been definitively shown to be a valid method for
      evaluating the therapeutic effect of an anti-hypertensive drug in a given
      patient, especially when resting levels are questioned. For therapeutic trials,
      ambulatory measurements serve as a reference to evaluate the effect of treatment
      on the circadian cycle. Peak/dip levels can thus be determined in comparison with
      the residual effect of the drug. A large number of studies remain to done to
      identify the full potential of this method.

PMID- 8545439
TI  - [Treatment of hypertension in the elderly].
AB  - Although an increase in the systolic pressure is a physiological phenomenon of
      the ageing process, the beneficial effect of treatment in the elderly, in terms
      of reducing risk of cerebral vascular events, heart failure and coronary artery
      disease, leads to a common definition of hypertension in adults. A subject is
      considered to have hypertension if the systolic pressure is greater than 160 mmHg
      or the diastolic pressure is greater than 95 mmHg. A subject whose blood pressure
      is less than 140/90 mmHg is considered to be normotensive. The rules and strategy
      for the prescription of antihypertensive drugs remain the same whatever the age
      of the patient. But, despite the large number of drugs available, it is often
      difficult to obtain normal levels in the elderly. Treatment should thus be based
      on a pragmatic strategy, setting the target level as a function of the initial
      blood pressure. A decrease of 20 to 30 mmHg in the systolic pressure should be
      considered as a satisfactory result. In the elderly patient, the rule should be
      to limit prescription to two drugs since these patients risk exposure to
      interactions with other pharmaceutical classes because of the multiple disease
      situations encountered. In case of "non-response" to a two-drug regimen, the
      physician should carefully question patient compliance, search for an
      unrecognized primary cause, and reconsider the validity of pressure assessment at
      consultation. A third drug cannot be justified unless non-response has been
      confirmed with ambulatory or self-measurement of blood pressure levels.

PMID- 8545440
TI  - [Enzyme converting inhibitors. Current knowledge and perspectives].
AB  - Angiotensin converting enzyme inhibitors (CEI) are logically proposed for the
      treatment of hypertension and heart failure because of their effect on reducing
      arteriol resistance. When administered early after myocardial infarction, CEI
      reduce mortality, particularly patients with severely deteriorated myocardium. Up
      to 74 lives can be saved for every 1000 patients treated. This beneficial effect
      is additive with that resulting from aspirin, beta-blockers and fibrinolysis. The
      effect occurs within the first month of treatment if initiated within the first
      24 hours following the infarction, and persists even if treatment is
      discontinued. Tolerance is generally good, but dosage must be adapted in case of
      hypotension or temporary renal failure. Macroproteinuric nephropathy in insulin
      dependent-diabetes is another indication for CEI. Captopril and enalapril have
      been shown to slow progression of renal failure and decrease the risk of death
      and of chronic dialysis. Further studies are being conducted to determine the
      effect of CEI in non-insulin-dependent diabetes. Finally, experimental arguments
      suggest that atherosclerosis is partly dependent on the renin/angiotensin system
      and that CEI might inhibit its development. Most clinical trials evaluating the
      action of CEI on atheromatosis have studied the effect in the carotid and
      coronary arteries.

PMID- 8545441
TI  - [Pharmaco-epidemiologic evaluation of rilmenidine in 18,235 hypertensive
      patients].
AB  - OBJECTIVES: Assess the effects of rilmenidine in routine clinical practice.
      METHODS: 18,235 patients with high blood pressure--mean age 61.2 years, arterial
      systolic pressure in supine position (SSP) over arterial diastolic pressure in
      supine position (SDP) at day 0: 174.58 +/- 0.12/101.51 +/- 0.06 mmHg--were
      followed by 2,072 general physicians. Treatment was initiated with a daily dose
      of 1 mg rilmenidine which was adapted as needed at different times in the study.
      At inclusion, diastolic pressure was between 90 and 115 mmHg in 84.5% of the
      patients; 1,126 patients had severe hypertension (SDP > or = 115 mmHg); 16,496 of
      these patients (81.5%) were followed for one year. RESULTS: Mean fall in blood
      pressure between day 0 and month 12 was -28.7/-19.3 mmHg in the overall study
      population and -27.4/-18.9 mmHg in patients treated with 1 mg/day. Mean fall in
      blood pressure was comparable in the 8 risk populations identified. The
      percentage of patients who achieved normalized blood pressure status was 96.2%
      (SDP < or = 90 mmHg); 59.1% with a 1 mg daily dose, 23.7% with 2 mg/day, 11.6%
      with two-drug treatment and 1.8% with three-drug treatment. Acceptability, taking
      into account all possible imputabilities (more than 35,000 coprescriptions) and
      associated diseases, the incidence of undesirable side effects never exceeded
      5.6% of the overall study population (5.2% in single-drug treatment, 8.3% in two-
      or three-drug treatment) and only 3.6% of the patients withdrew from the study
      due to an undesirable effect whether imputable to the treatment or not. There was
      little change in heart rate (mean--3 beats per minute between day 0 and month
      12); variations observed depended on the rate at study onset. Laboratory tests
      (blood glucose, cholesterol, triglycerides, potassium, creatinine, uric acid)
      were not changed in any of the population groups. CONCLUSIONS: This pharmaco
      epidemiologic study showed that the benefit/acceptability ratio for rilmenidine
      is quite satisfactory and confirms the contribution of rilmenidine as first line
      treatment for hypertension.

PMID- 8545442
TI  - The origin of trisomy in humans.

PMID- 8545443
TI  - Proceedings of the International Down Syndrome Research Conference. Charleston,
      South Carolina, April 11-13, 1994.

PMID- 8545444
TI  - Dissociation of galaninergic and neurotrophic plasticity in Down syndrome and
      Alzheimer disease.

PMID- 8545445
TI  - Magnetic resonance imaging of the aging brain in Down syndrome.
AB  - MRI studies to date have confirmed and expanded upon findings of morphologic
      differences between the brains of subjects with DS and those of the general
      population found by CT and post-mortem examination. [table; see text] Hippocam
      pal and neocortical structures are smaller in DS while unexpectedly the
      parahippocampal gyrus was found to be larger. MRI has demonstrated that subjects
      with DS develop signs associated with [table; see text] brain aging at an earlier
      age. These findings include increased rate of dilatation of ventricles, increased
      peripheral atrophy, and increased deep white matter lesions. In addition, changes
      that are associated with AD occur earlier in the DS population. Functional
      studies reveal decreasing cerebral perfusion with age in adults with DS, a
      pattern similar to non-DS subjects with clinically progressive dementia, and
      provide evidence for altered blood-brain barrier permeability. Dynamic MRI
      studies have also shown adults with DS to have fluctuating cortical CSF volumes,
      similar to some elderly non-DS subjects and subjects with shunted hydrocephalus.
      This is a new finding in brain aging that suggests a relationship between aging
      in DS and edematous states of the brain.

PMID- 8545446
TI  - Mechanism of chromosome nondisjunction in human oocytes.

PMID- 8545447
TI  - Genetic determinants of Alzheimer disease.

PMID- 8545448
TI  - A hypothesis to explain the immune defects in Down syndrome.

PMID- 8545449
TI  - Down syndrome and leukemia, an update.
AB  - Acute leukemia (AL) is a relatively uncommon, but dreaded, complication occurring
      with increased frequency in individuals with Down syndrome (DS). This selective
      update includes aspects of AL in DS in which a change or advancement in our
      understanding of this disease has occurred. Despite previous reports describing a
      worse outcome for these individuals, more recent studies have suggested an
      improved response to current treatment strategies (including high-dose AraC)
      equaling, or even surpassing, the survival of non-DS individuals with AL. An
      increased toxicity to methotrexate in DS patients has also been recognized. While
      the leukemia of DS infants has been described as megakaryoblastic, the spectrum
      of in vitro differentiation is much broader including (in addition to
      megakaryocytic colonies) various myeloid, macrophage, and even erythroid
      colonies. Although the cause(s) of DS-AL remains unknown, potential candidate
      genes include those encoded on chromosome 21 that play a role in other defined
      leukemias in non-DS individuals. The AML1/PEBP2alpha gene maps to the DS critical
      region and is characteristically associated with two leukemia-associated
      chromosomal translocations: 1) the 8;21 translocation involving an AML1/ETO
      fusion transcript commonly seen in acute myelogenous leukemia (AML) and; 2) a
      3;21 translocation identified in certain chemotherapy-related
      myelodysplasias/leukemias and occasionally in the blast crisis of chronic
      myelogenous leukemia cells. Similarly, the ETS-related gene, ERG, involved in the
      AML 16;21 maps to the q22 region of chromosome 21. Lastly, a familial platelet
      disorder with a propensity to develop myeloid leukemia has been linked to 21q22.1
      22.2 and conceivably might involve AML1, ERG or yet another gene.

PMID- 8545450
TI  - Considerations of quantitative data on organ sizes and cell numbers and sizes in
      Down syndrome.

PMID- 8545451
TI  - Transgenic models for chromosome 21 gene dosage effects.

PMID- 8545452
TI  - YAC transgenic mice in the study of the genetic basis of Down syndrome.

PMID- 8545453
TI  - Preliminary characterization of the central nervous system in partial trisomy 16
      mice.

PMID- 8545454
TI  - Epilogue: toward the twenty-first century with Down syndrome--a personal view of
      how far we have come and of how far we can reasonably expect to go.

PMID- 8545455
TI  - Antenatal screening for Down syndrome.
AB  - Antenatal screening for Down syndrome was introduced a quarter of a century ago.
      The risk of fetal loss due to amniocentesis and the costs of the procedure
      restrict antenatal diagnosis to women who are at high risk of having an affected
      pregnancy. Initially the only method of screening women to identify older women
      for the diagnostic test. In 1988, the introduction of antenatal serum screening
      using various biochemical markers together with maternal age improved the
      performance of screening considerably - the proportion of affected pregnancies
      identified in the 5% of women of highest risk increased from about 30% to over
      60%. Current research is continuing to refine the screening methods to improve
      screening performance by the addition of new markers, by the combination of serum
      and ultrasound markers, and by carrying out screening earlier in pregnancy.
      Improvements in the technical quality of screening needs to be matched by
      continuing attention to the quality of the screening service and ensuring that
      the public are satisfied with the service.

PMID- 8545456
TI  - The integrated map of human chromosome 21.

PMID- 8545457
TI  - Cognitive abilities in children with Down syndrome: developmental instability and
      motivational deficits.

PMID- 8545458
TI  - Individual differences in vocabulary acquisition in children with Down syndrome.
AB  - Children with Down syndrome offer an opportunity for investigators interested in
      cognition and language problems to study asynchronous development of vocabulary,
      and syntax in language production relative to comprehension and cognitive status.
      Our work to date has documented consistent differences in the rate of vocabulary
      learning in children with DS relative to their mental age matched peers. These
      deficits increase with advancing age indicating that the learning rate of the DS
      group is significantly slower than that of the TD group. While the rate of
      vocabulary acquisition is significantly slower for the children with DS, not all
      of the children we studied exhibited similar rates of learning. Thirty-five
      percent of our children had rates of vocabulary growth consistent with mental age
      expectations. These data suggest that neither the syndrome alone nor the
      cognitive deficit associated with Down syndrome can explain the differences
      observed in vocabulary growth. Our next series of studies will evaluate a variety
      of causal constructs to explain the significant asynchronies in language learning
      compared with other cognitive abilities.

PMID- 8545459
TI  - Antiepileptic drugs--their effects on kindled seizures and kindling-induced
      learning impairments.
AB  - Many epileptic patients suffer from cognitive impairments. These impairments may
      be a consequence of the epileptogenic process and/or antiepileptic medication.
      Kindling is considered a useful experimental model to investigate drug effects on
      both the convulsive component of epilepsy and related alterations at the
      behavioral level. In our experiments, kindling was induced by repeated injections
      of pentylenetetrazol (PTZ). To test the effect of antiepileptic drugs on kindled
      seizures and kindling-induced learning deficits we injected ethosuximide,
      dipropylacetate, and phenobarbital prior to each kindling stimulation or after
      kindling completion, and tested these animals in a shuttle-box paradigm.
      Dipropylacetate and phenobarbital suppressed the development of motor seizures
      and counteracted the learning deficit. Although ethosuximide had a clear effect
      on kindled seizures, the learning deficit occurred in kindled rats. This suggests
      that AEDs effects on kindled seizures are not correlated with the elimination of
      deficits in the field of cognition.

PMID- 8545460
TI  - Caffeine and selective visual processing.
AB  - This work addressed five issues: a) Does caffeine modulate electroencephalogram
      (EEG) background activity in a manner consistent with the idea of cortical
      "arousal"? b) Is performance in a simple speeded task improved under caffeine? c)
      Is visual processing more selective under caffeine? d) Does caffeine affect
      sensory discrimination? and e) Does it affect motor processes? We presented 16
      subjects with a visual selection task under conditions of either caffeine or
      placebo. Background EEG data, gathered before administration of the task,
      revealed that caffeine resulted in lower slow-alpha power, relative to placebo,
      which is consistent with the idea of increased cortical "arousal." During the
      selection task, subjects had to respond manually to a given target conjunction of
      spatial frequency and orientation. Other conjunctions shared spatial frequency,
      orientation, or neither with the target. The four conjunctions were presented in
      a random sequence, with SOAs ranging between 750 and 950 ms. Event-related
      potentials (ERPs) to the conjunctions were recorded at standard scalp locations
      Fz, Cz, Pz, and Oz. Under caffeine, subjects made faster responses to target
      conjunctions (382.9 vs. 404.5 ms) and more hits, whereas the false-alarm rate was
      equal across conditions. Caffeine did not affect the selection potentials
      normally obtained in this task by subtracting, from ERPs to nontargets with the
      target spatial frequency, those to nontargets with the other frequency. However,
      an early differential positivity (50-160 ms) was found specifically under
      caffeine, indicative of increased selectivity. Difference ERPs as a function of
      physical parameters were not affected by caffeine, indicating no effect on
      sensory discrimination. Onsets of response-related lateralizations above the
      motor cortex were not affected by caffeine, suggesting that the shorter reaction
      times under caffeine were due to faster central or peripheral motor processes.

PMID- 8545461
TI  - Ethological comparison of the effects of diazepam and acute/chronic imipramine on
      the behaviour of mice in the elevated plus-maze.
AB  - Recent clinical evidence suggests that the tricyclic antidepressant imipramine is
      effective against not only panic disorder but also generalized anxiety disorder.
      Although most animal models of anxiety appear to be insensitive to this agent,
      such work has almost invariably employed an acute treatment regimen. In the
      present study, ethological methods have been used to assess in detail the effects
      of acute and chronic imipramine treatment on the behaviour of male DBA/2 mice in
      the elevated plus-maze test. In contrast to acutely administered diazepam (1
      mg/kg), which produced a significant anxiolytic profile on standard and
      ethological measures, neither acute nor chronic (daily, 15 days) treatment with
      imipramine (0-20 mg/kg) was associated with anxiety reduction. Data are discussed
      in relation to test sensitivity factors and the nonspecific mechanism of action
      of imipramine.

PMID- 8545462
TI  - Some behavioural and neurochemical aspects of subacute (+/-)3,4
      methylenedioxymethamphetamine administration in rats.
AB  - (+/-)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"), an increasingly popular
      recreational drug, is known to damage brain serotonin (5-hydroxytryptamine [5
      HT]) neurons, whilst also having a less pronounced effect on the dopaminergic
      system. Treatment with MDMA results in an increased locomotor activity, elevated
      basal serum corticosterone concentrations, decreased exploratory activity, and
      changes in body temperature. The aim of this study was to examine the dose
      related effects of subacute administration of MDMA (5, 10, and 20 mg/kg IP twice
      daily for 4 days) on home cage locomotor activity, "open field" and "step-down
      passive avoidance" behaviours, changes due to an 8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT) challenge, and on plasma corticosterone and brain
      neurotransmitter concentrations. Total locomotor activity counts were
      significantly increased by both 10 and 20 mg/kg MDMA for the 4 days of drug
      administration. There were no significant differences seen in the "open field" or
      "step down passive avoidance" behaviour, in the 8-OH-DPAT induced hypothermia, or
      in basal serum corticosterone concentrations. MDMA caused a significant depletion
      of both 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex and
      amygdala and a significant elevation of dopamine and noradrenaline in the
      hippocampus. Apart from the increase in locomotor activity following subacute
      administration, the observed behaviour of the MDMA treated rats would not appear
      to reflect the substantial changes in brain biogenic amine neurotransmitters.

PMID- 8545463
TI  - Atropine increases pilocarpine-induced yawning behavior in paradoxical sleep
      deprived rats.
AB  - Paradoxical sleep (PS) deprivation has been suggested to induce supersensitivity
      of postsynaptic dopamine (DA) receptors and subsensitivity of acetylcholine (ACh)
      receptors. Yawning behavior is reduced after PS deprivation and is believed to
      result from an interaction between ACh and DA systems. Concomitant treatment of
      PS deprived animals with DA agonists reverses PS deprivation effects on
      stereotypy and aggressiveness. To examine this possibility on yawning behavior,
      rats were treated, during the deprivation period, with atropine, methamphetamine,
      haloperidol or distilled water. Following PS deprivation, rats were injected with
      apomorphine or pilocarpine and number of yawns was recorded. Atropine increased
      yawning of PS deprived rats induced by pilocarpine, but not by apomorphine.
      Treatment with methamphetamine and haloperidol did not change PS deprivation
      effect on pilocarpine- and apomorphine-induced yawning. The data suggest that
      reversal of PS deprivation-induced yawning inhibition is mediated distinctly by
      both acetylcholine and dopamine systems.

PMID- 8545464
TI  - Suppression of cortical epileptic afterdischarges by ketamine is not stable
      during ontogenesis in rats.
AB  - Anticonvulsant action of ketamine, a noncompetitive NMDA antagonist, was studied
      in three groups of immature rats (12-, 18-, and 25-day-old) using cortically
      elicited epileptic afterdischarges (ADs) as a model. Rats with implanted
      electrodes were used, so that EEG and motor phenomena could be recorded.
      Stimulation (bipolar pulses of 1-ms duration and 8-Hz frequency) lasting 15 s was
      repeated four times with intervals of 10 min. Ketamine was administered IP 5 min
      after the first AD in doses of 5, 10, 20, or 40 mg/kg. Control groups did not
      receive any drug. Ketamine shortened ADs and suppressed motor correlates of
      stimulation as well as of ADs in a dose-dependent manner in 12- and 25-day-old
      rats. No significant changes were observed in 18-day-old animals, demonstrating
      thus a rather complicated development of anticonvulsant action of ketamine. Not
      only NMDA antagonism, but also other possible effects of ketamine must be taken
      into account.

PMID- 8545465
TI  - Serotonergic stimulation of the ventrolateral striatum induces orofacial
      stereotypy.
AB  - Dopaminergic (DA) stimulation of the ventrolateral striatum produces a syndrome
      of intense orofacial stereotypies. In addition to dopaminergic projections from
      the substantia nigra, the striatum receives serotonergic (5-HT) inputs arising
      from the raphe nuclei. To assess the putative role of striatal 5-HT in orofacial
      movements, serotonin (0, 0.2, 2, 10, 20 micrograms/1.0 microliters) was infused
      into the ventrolateral striatum and behaviors were recorded using a time-sampling
      procedure. Serotonin produced a dose-dependent, site-specific increase in
      stereotyped orofacial behaviors. Infusion of selective 5-HT receptor agonists or
      uptake inhibitors did not produce the orofacial syndrome and pretreatment with
      either selective or nonselective 5-HT receptor antagonists did not block the 5-HT
      induced stereotypy. In contrast, pretreatment with DA receptor antagonists
      completely abolished the 5-HT induced repetitive orofacial movements, providing
      evidence for a 5-HT/DA interaction at this site. Moreover, depletion of DA with a
      combination of reserpine and alpha-methyl-p-tyrosine markedly decreased the
      stereotyped behaviors induced by 5-HT microinfusion. These data provide evidence
      for an interaction between 5-HT and DA in the striatum at presynaptic DA
      terminals. It is hypothesized that 5-HT may cause release of DA via reversal of
      the DA transporter. This syndrome may provide an animal model for some aspects of
      obsessive-compulsive disorder, because current theories of this disorder
      implicate 5-HT dysfunction in the basal ganglia.

PMID- 8545467
TI  - Proline, ascorbic acid, or thioredoxin affect jaundice and mortality in Long
      Evans cinnamon rats.
AB  - The Long Evans Cinnamon (LEC) rat spontaneously develops fulminant hepatitis,
      which is usually lethal due to excess copper accumulation in the liver and is
      considered an animal model of Wilson's disease. LEC rats show a strong appetite
      for proline solution. Daily oral (p.o.) administration of proline resulted in
      significant delay of mortality. Feeding a copper-deficient diet greatly delayed
      the onset of jaundice and mortality and voluntary consumption or p.o.
      administration of proline further delayed jaundice and prevented mortality. LEC
      rats also consume ascorbic acid solutions, and p.o. administration of ascorbate
      also results in a significant delay in the appearance of jaundice and mortality.
      Combined treatment with ascorbic acid and proline is additive to delay further
      jaundice and mortality. An endogenous antioxidant protein, thioredoxin, when
      infused by minipump IP, could also inhibit the incidence of jaundice. These
      results indicate that antioxidant treatment combined with proline may be of
      benefit in Wilson's disease and possibly other forms of hepatic dysfunction.

PMID- 8545466
TI  - Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on
      yawning, stereotypy, and body temperature in rats.
AB  - 7-OH-DPAT ((+/-)-2-(dipropylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene) was
      recently identified as a dopamine receptor agonist having a > 100-, 1,000- and >
      10,000-fold higher affinity for dopamine D3 than for D2, D4 and D1 receptors,
      respectively. Quinpirole (LY 171555) has also been reported to have a 113-fold
      greater affinity for dopamine D3 receptors than for D2 receptors. Therefore, we
      investigated the effects of these putative dopamine D3 receptor agonists on
      yawning, stereotypy and rectal temperature in rats (N = 424). 7-OH-DPAT and
      quinpirole administered subcutaneously (SC) at respective low doses of 10-250
      micrograms/kg and 25-500 micrograms/kg elicited yawning behavior. The yawning
      induced by these agents was blocked by spiperone (0.5 mg/kg, SC) and scopolamine
      (0.5 mg/kg, SC) but was increased by intraperitoneal (IP) administration of
      pindolol (20 mg/kg). The yawning was also potentiated after treatment with
      reserpine. 7-OH-DPAT and quinpirole at respective high doses of 0.25 mg/kg (SC)
      and 0.5 mg/kg (SC) evoked slight stereotypy such as sniffing and licking, and
      this effect was enhanced by a selective dopamine D1 receptor agonist, SK&F 38393
      (1-phenyl-2,3,4,5,-tetrahydro-(1H)-3-benzazepine-7,8-diol). 7-OH-DPAT (0.5 mg/kg,
      SC) and quinpirole (0.5 mg/kg, SC) decreased, but SK&F 38393 (10 mg/kg, SC)
      increased body temperature. However, the hyperthermia induced by SK&F 38393 was
      interestingly enhanced by 7-OH-DPAT and quinpirole.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8545468
TI  - Nicotine enhances the learning and memory of aged rats.
AB  - The cognitive performance of young adult (2-3-month-old) and aged (22-24 month
      old) rats was characterized in one of three different behavioral tasks, and the
      ability of daily nicotine treatment to alleviate age-related learning and memory
      deficits was evaluated. Aged rats received an IP injection of either nicotine
      (0.2 mg/kg) or saline vehicle 15 min prior to daily testing; young control rats
      received saline vehicle injections. Compared to young controls, aged control rats
      were severely impaired in the acquisition of one-way active avoidance pole
      jumping over 12 days of testing. Nicotine pretreatment of similar aged rats
      markedly improved overall learning and the rate of learning compared to aged
      controls. In Lashley III maze performance, aged control rats made substantially
      more alternation errors than young controls; however, aged rats pretreated with
      nicotine made significantly fewer errors over the entire 20-day test period
      compared to aged controls. During 30 days of 17-arm radial maze testing, aged
      control animals were severely impaired in general learning and reference (long
      term) memory, but only mildly impaired in working (short-term) memory. Nicotine
      pretreatment of similar aged rats induced a substantial enhancement in overall
      learning and reference memory, but did not affect working memory. These results
      indicate that chronic nicotine administration can improve the impaired
      learning/memory abilities of aged rats in several tasks, and suggest that
      stimulation of central nicotinic receptors may be of considerable therapeutic
      value to treat age-related memory impairment.

PMID- 8545469
TI  - Operant response suppression induced with systemic administration of 5
      hydroxytryptophan is centrally mediated.
AB  - Intracerebroventricular (ICV) administration of selective serotonergic agents was
      used to examine the extent of central mediation of 5-HTP-induced operant response
      suppression in rats. ICV administration of LY53857 (1.0, 3.75, or 7.5
      micrograms/5 microliters/5 min) dose dependently blocked response suppression
      induced with systemically administered 5-HTP (25 mg/kg, IP), whereas ICV 0.9%
      saline (5 microliters over 5 min) had no significant effect on 5-HTP-induced
      response suppression. ICV ketanserin (7.5 micrograms/5 microliters/5 min) also
      blocked response suppression induced with systemically administered 5-HTP. ICV
      administration of the 5-HT2A/2C receptor agonist DOI (80 micrograms/5
      microliters/5 min) induced significant periods of response suppression in this
      model, which was blocked with LY53857 (1.0 mg/kg, IP) pretreatment. These data
      demonstrate that central administration of 5-HT2A/2C antagonists potently
      attenuate operant response suppression induced with systemically administered 5
      HTP or DOI and are in agreement with previous findings suggesting central
      mediation of 5-HTP-induced operant response suppression.

PMID- 8545470
TI  - Contingent drug tolerance: differential tolerance to the anticonvulsant,
      hypothermic, and ataxic effects of ethanol.
AB  - The kindled-convulsion model of epilepsy was used to study contingent tolerance
      to ethanol's (1.5 g/kg; IP) anticonvulsant, hypothermic, and ataxic effects in
      adult male rats. In the present experiments, three groups of amygdala-kindled
      rats received a series of bidaily (one every 48 h) convulsive stimulations: one
      group received ethanol 1 h before each stimulation; one group received ethanol 1
      h after each stimulation; and another group served as the saline control.
      Tolerance to ethanol's anticonvulsant effect (Experiments 1 and 2) was greatest
      in those rats that received ethanol before each convulsive stimulation; whereas,
      tolerance to ethanol's hypothermic (Experiments 1 and 2) and ataxic (Experiments
      2) effects developed in both groups that received ethanol. These results were
      predicted on the basis of the drug-effect theory of drug tolerance: the theory
      that functional drug tolerance is an adaptation to the disruptive effects of
      drugs on concurrent patterns of neural activity, not to drug exposure per se.

PMID- 8545471
TI  - The inhibitory effects of propranolol on genital reflexes in male rats.
AB  - We have previously reported that propranolol adversely affects sexual behavior in
      male rats. To elucidate whether the effects of propranolol might involve
      decrements in ability, we examined two components of sexual function ex copula-
      ejaculatory reflex capacity and erectile reflexes. In the first study, we
      examined the effects of various doses of (+/-)-propranolol (1.25-10 mg/kg)
      administered subcutaneously. Marked inhibition was observed, evidenced by
      increases in the latency to ex copula ejaculation and to initial erection and
      decrements in the number of seminal emissions and in the number of erectile
      reflexes. Analyses of dose-response relationships indicated that the degree of
      inhibition increased with increasing dose. In the second study, we evaluated the
      stereo-selectivity of the responses. Both (+)- and (-)-propranolol (1.25 mg/kg)
      significantly inhibited ejaculatory reflex potential, and although (+)- and (-)
      propranolol significantly inhibited erectile reflexes, (-)-propranolol had a
      greater effect. The data are interpreted to indicate that a) propranolol-induced
      sexual dysfunction involves both motivational and ability aspects; and b)
      propranolol-induced inhibition of genital reflexes may be due, at least in part,
      to mechanisms other than beta-adrenoceptor blockade.

PMID- 8545472
TI  - Protein kinase inhibitors disrupt memory formation in two chick brain regions.
AB  - The amnesic effects of protein kinase inhibitors (H-7, HA-156, TFP, W-9, and W
      13) on memory formation for a one trial peck-avoidance task in chicks were
      investigated with bilateral and unilateral injections into either the left or the
      right intermediate medial hyperstriatum ventrale (IMHV) or the left or right
      lobus parolfactorius (LPO). All five inhibitors injected bilaterally 5 min
      pretraining into either the IMHV or LPO or unilaterally into the left IMHV
      produced amnesia. Unilateral injections into the right IMHV did not produce
      amnesia. Unilateral injections of W-9 or W-13 into the left but not the right LPO
      produced amnesia, H-7, HA-156, or TFP did not produce amnesia when injected
      unilaterally into either the left or right LPO. The time of onset of amnesia
      produced by injecting TFP and W-13 into the LPO occurred 45 min after training,
      whereas H-7 produced amnesia significantly later (90 min after training). Amnesia
      induced by TFP, W-13, and H-7 injected into the LPO occurred significantly later
      than amnesia produced when these agents were injected into the IMHV. Together
      these data suggest that the IMHV and LPO process memory sequentially using
      various protein kinase activities.

PMID- 8545473
TI  - Prostacyclin analogue TTC-909 reduces memory impairment in rats with cerebral
      embolism.
AB  - The effects of the stable prostacyclin analogue TTC-909 on memory impairment in
      the water maze task and on neuronal damage were studied in rats with cerebral
      embolism induced by injecting polyvinyl acetate (PVA) into the right internal
      carotid artery and the ensuing embolism extending out into the right middle
      cerebral artery. Areas supplied by the lenticulostriate artery were most markedly
      damaged. In the water maze test, the PVA-embolized rats took longer to reach the
      platform than did the nontreated control rats. To some extent, repeated
      administrations of TTC-909 (200 ng/kg, IV) overcame this impairment in water maze
      learning in the rats. We assume that the vasodilating effects of TTC-909 maintain
      this blood supply to the ischemic area and that TTC-909 prevents the development
      of thrombosis around the PVA particles in the arterial capillaries, as a result
      of antiplatelet aggregative effects. These two mechanisms are likely to be
      involved in memory improvement. TTC-909 may prove effective for treating subjects
      with stroke and other cerebrovascular disorders.

PMID- 8545474
TI  - Oxymorphone-induced analgesia and colonic motility measured in colorectal
      distension.
AB  - Changes in colonic motility in rats following intravenous (IV) oxymorphone (0.1
      mg/kg), atropine (0.1 mg/kg), or saline were monitored to determine whether
      opioid-induced changes in colonic motility affect antinociceptive measurements
      when using colorectal distension (CRD) as a nociceptive assay. Polygraph
      recordings of colonic pressures, contraction frequencies, and the pressure-volume
      relationship of the stimulus showed that oxymorphone produced a transient
      increase in contraction frequencies when compared to atropine- and saline-treated
      rats. The transient increase in contraction frequency caused by oxymorphone
      declined to baseline levels at 30 min after administration, the time at which the
      nociceptive threshold for CRD was tested. Neither oxymorphone nor atropine
      changed baseline pressures or the pressure-volume curve for the balloon stimulus.
      Antinociceptive results from CRD at 30 min posttreatment showed that only
      oxymorphone produced significant antinociception. We conclude that oxymorphone
      does not produce changes in colonic motility that complicate antinociceptive
      measurements in CRD and that CRD is an effective means of testing opioid-induced
      visceral antinociception.

PMID- 8545475
TI  - The elevated plus-maze is not sensitive to the effect of stressor controllability
      in rats.
AB  - The present experiments examined the sensitivity of the elevated plus-maze to the
      effects of stressor controllability. Previous work had established that
      inescapable but not an equal amount of escapable electric tail shock reduced
      social interaction. The present experiments demonstrate that prior exposure to
      shock alters elevated plus-maze behavior, but that this effect is not sensitive
      to the escapability of the shock. These experiments include a replication of the
      usual pharmacologic effects of benzodiazepine ligands (2 mg/kg diazepam; 0.4
      mg/kg methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) to demonstrate
      the sensitivity of the elevated plus-maze procedures used. The results provide
      additional support for the idea that the social interaction and elevated plus
      maze measures of "anxiety" are sensitive to different processes.

PMID- 8545476
TI  - Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3
      antagonists in the pigeon.
AB  - Vomiting may be induced by a variety of agents such as drugs, oncolytics, and
      provocative motion, as well as being conditioned to occur to environmental
      stimuli. Such emesis has recently been shown to be blocked by agonists at the 5
      HT1A subtype of serotonin receptor. The antiemetic effects of LY228729 [(-)-4
      (dipropylamine)-1,3,4,5-tetrahydrobenz-(c,d)indole-6- carboxamide], a 5-HT1A
      receptor agonist, were tested and compared to the antiemetic effects of the 5-HT3
      receptor antagonists ondansetron, tropisetron, and MDL 72222 (3-tropanyl-3,5
      dichlorobenzoate). The emetic stimuli tested are known to be blocked by 5-HT3
      antagonists in species other than the pigeon. In the pigeon, LY228729 totally
      abolished vomiting induced by fully emetic doses of cisplatin (10 mg/kg), ipecac
      (3 ml/kg), emetine (10 mg/kg), and a 5-HT3 agonist, m-(chlorophenyl)-biguanide
      (1.25 mg/kg). MDL 72222 blocked ipecac-induced vomiting in a dose-related manner
      and was partially effective in attenuating cisplatin-induced emesis. Ondansetron
      and tropisetron were partially effective in blocking emetine- and mCPBG-induced
      vomiting. Ondansetron exhibited an intrinsic emetic response that could not be
      blocked by MDL 7222, but which was eliminated by LY228729. It was concluded that
      5-HT1A agonists are more effective in the pigeon than are 5-HT3 antagonists
      against these types of emetic stimuli. These results broaden the range of emetic
      stimuli that are blocked by 5-HT1A agonists in the pigeon.

PMID- 8545477
TI  - Chronic treatments with 5-HT1A agonists attenuate posthypoxic myoclonus in rats.
AB  - Following 10 min cardiac arrest and resuscitation, male Sprague-Dawley rats
      developed posthypoxic myoclonus. This phenomenon peaked at 14 days and
      disappeared by 60 days after cardiac arrest. From previous results, the 5
      hydroxytryptamine (5-HT) system was implicated in the pathogenesis of the
      disease. In the present study, we investigated the involvement of 5-HT1A
      receptors in posthypoxic myoclonus in rats. Single injections of 5-HT1A agonists,
      buspirone (5 and 10 mg/kg body wt.) or 8-OH-DPAT (1, 2, and 4 mg/kg), had no
      effect on either the intensity or time course of the disease. In contrast,
      multiple injections (twice a day for 7 or more days) of buspirone (10 mg/kg) or 8
      OH-DPAT (4 mg/kg) significantly attenuated the myoclonus scores of animals (p <
      0.05). The results indicate that chronic stimulation of 5-HT1A receptors in the
      brain may accelerate endogenous compensatory mechanisms and shorten the time
      course of the disease.

PMID- 8545478
TI  - Chronic clozapine selectively decreases prefrontal cortex dopamine as shown by
      simultaneous cortical, accumbens, and striatal microdialysis in freely moving
      rats.
AB  - We used microdialysis to study the acute and chronic effects of clozapine on the
      metabolism of dopamine (DA) in terminal areas of the mesocortical, mesolimbic,
      and nigrostriatal systems simultaneously. In the acute experiment, groups of four
      rats received the following doses: 0 (vehicle), 10, 20, and 40 mg/kg of clozapine
      subcutaneously, which resulted in a dose-related increase in extracellular DA,
      3,4-dihydroxyphenalacetic acid (DOPAC), and homovanillic acid (HVA) in the
      prefrontal cortex (PFC). In the nucleus accumbens (NAC) and striatum (STR), no
      significant changes were observed at any dose. In the chronic experiment, six
      rats received 20 mg/kg of clozapine and a control group received vehicle daily
      for 30 days. After 30 days of treatment, DA, DOPAC, and HVA were significantly
      lower in the PFC, and unchanged in the NAC or STR. The 30th clozapine injection
      failed to increase DA, DOPAC, or HVA in any of the three regions. We conclude
      that clozapine acted selectively on the mesocortical system, and that this may
      underlie clozapine's therapeutic, antipsychotic effect.

PMID- 8545479
TI  - Oxytocin blocks the development of heroin-fentanyl cross-tolerance in mice.
AB  - The development of cross-tolerance to an analgesic effect was observed between
      two mu-receptor agonists, heroin and fentanyl. Repeated treatments with heroin
      twice a day for 4 days resulted in a decreased nociceptive effect to fentanyl on
      day 5. The fentanyl dose-response line shifted to the right, and was considered
      to be a sign of the development of cross-tolerance. Peripheral treatment with
      oxytocin did not block the development of heroin-fentanyl cross-tolerance.
      However, intracerebroventricular administration of oxytocin blocked the
      development of tolerance, causing a leftward shift in the dose-response curve and
      supporting the assumption that oxytocin blocks the development of heroin-fentanyl
      cross-tolerance via CNS mechanisms.

PMID- 8545480
TI  - Effects of calcitonin gene-related peptide on acute and chronic effects of
      morphine.
AB  - Calcitonin gene-related peptide (CGRP), which has been observed in different
      parts of the nervous system, is known to modify pain sensitivity to different
      stimuli in rats and mice. The aim of this study was to investigate the possible
      interaction of CGRP with morphine on nociception in adult male NMRI mice after
      central administration of the peptide. CGRP (20 or 200 ng) did not itself modify
      pain sensitivity in the tail-flick test and did not affect the acute
      antinociceptive action of a single dose of morphine in the same test. However,
      CGRP suppressed the development of rapid tolerance to morphine in a dose
      dependent manner, but had no action on the development of chronic tolerance to
      morphine and on manifestations of naloxone-precipitated withdrawal syndrome.

PMID- 8545481
TI  - Effects of varying temporal exposure to lead on behavioral development in herring
      gull (Larus argentatus) chicks.
AB  - In humans and other animals, lead exposure in infants and young animals affects
      anatomic, physiologic, behavioral, and intellectual development. Yet it is
      largely unknown whether the effects occur gradually or are more pronounced if
      exposure occurs at particular stages. In this article we examine the effects of
      temporal differences in lead exposure on early behavioral development in herring
      gulls (Larus argentatus). We randomly assigned 64 1-2-day-old gull chicks to one
      of four treatment groups to receive a lead acetate dose at age 6 days (100
      micrograms/g) or 12 days (50 or 100 micrograms/g), or to receive matched volume
      saline injections on the same days. Behavioral tests were performed at 2-5-day
      intervals to examine locomotion, balance, righting response, thermoregulation,
      and visual cliff. Flight behavior was examined at fledging. Results were compared
      with previously studied exposures at 2, 4, and 6 days of age. Righting response
      and balance were disrupted immediately after exposure, regardless of the timing
      of exposure. Thermoregulatory, visual cliff, and individual recognition behavior
      were more affected by exposure at 2-6 days, and there was little effect with
      exposure at 12 days. These results confirm the existence of critical periods for
      certain behaviors to lead exposure in developing herring gulls.

PMID- 8545482
TI  - D-cycloserine enhances rapid tolerance to ethanol motor incoordination.
AB  - In a recent study, we showed that D-cycloserine, an agonist at the glycine site
      of the NMDA receptor, enhances the development of rapid tolerance to ethanol. In
      the present study, we report that the acquisition of rapid tolerance to the motor
      incoordination effect of ethanol (tilt-plane test) was increased only when D
      cycloserine was injected before, but not after, the intoxicated practice under
      ethanol. The effect of D-cycloserine on tolerance when this agonist was
      administered in divided doses before and after test was similar to that obtained
      when D-cycloserine was injected before test. Higher doses of D-cycloserine did
      not produce a further enhancement of rapid tolerance. Moreover, when the dose of
      ethanol on day 1 was large enough to induce rapid tolerance per se, D-cycloserine
      did not further enhance the tolerance. The enhancement of tolerance by D
      cycloserine was antagonized by previous administration of ketamine. The
      enhancement of ethanol tolerance by D-cycloserine and the antagonism of this
      effect by ketamine cannot be attributed to changes in pharmacokinetics of
      ethanol. Taken together, these results confirm the participation of the NMDA
      receptor system in the development of tolerance to ethanol, and reinforce earlier
      findings about the involvement of learning in tolerance.

PMID- 8545483
TI  - Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring
      rats.
AB  - Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol-accepting (AA) rats were
      injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10,
      30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were
      administered intragastrically (IG) with either 60 mg/kg of Ibogaine or vehicle
      for 5 days. In addition, the effects of Ibogaine on blood alcohol concentrations
      were measured. Our data show that, contrary to the SC administration of Ibogaine,
      IP administration of the agent significantly and dose-dependently reduced alcohol
      intake in these rats. Subchronic IG administration of 60 mg/kg of Ibogaine into
      FH rats significantly reduced alcohol intake without the development of tolerance
      or a significant effect on food or water intake. A single IP injection of 60
      mg/kg Ibogaine into FH rats did not affect the blood alcohol levels. These
      results show that Ibogaine when injected IP or IG, but not SC, can significantly
      reduce alcohol intake without an effect on blood alcohol concentrations or food
      intake. These findings may suggest the involvement of Ibogaine's metabolite(s) in
      reducing alcohol intake. Although the neuronal mechanism(s) of action of Ibogaine
      on the regulation of alcohol intake is not fully understood, it is speculated
      that Ibogaine or its metabolite(s) exerts its attenuating effect on alcohol
      intake by modulating neurotransmitters/neuromodulators proposed to be involved in
      regulation of alcohol consumption.

PMID- 8545484
TI  - Antidepressant-like actions of the polyamine site NMDA antagonist, eliprodil (SL
      82.0715).
AB  - Functional N-methyl-D-aspartate (NMDA) antagonists including competitive
      antagonists, glycine partial agonists, and use-dependent channel blockers exhibit
      antidepressant-like actions in preclinical models. The present study examined the
      effects of eliprodil (SL-82.0715), an NMDA antagonist acting at polyamine sites,
      in behavioral and neurochemical tests predictive of antidepressant activity. In
      mice, eliprodil produced a dose-dependent reduction in immobility in the forced
      swim test, but was inactive in the tail suspension test. Chronic treatment with
      eliprodil produced both a significant downregulation of beta-adrenoceptors and a
      reduction in the potency of glycine to inhibit [3H]5,7-dichlorokynurenic acid
      binding to strychnine-insensitive glycine receptors in neocortical membranes. In
      toto, these data indicate that like other NMDA antagonists, eliprodil possesses
      antidepressant-like actions in preclinical tests predictive of clinical efficacy.

PMID- 8545485
TI  - Corticosterone reversibly alters brain alpha-bungarotoxin binding and nicotine
      sensitivity.
AB  - Previous studies have shown that chronic corticosterone (CCS) treatment via
      subcutaneous pellets elicits reduced sensitivity to many actions of nicotine in
      mice as well as decreased brain alpha-bungarotoxin (alpha-BTX) binding. We report
      here the time courses of altered sensitivity to nicotine, as measured by acoustic
      startle, Y-maze crossing and rearing activities, heart rate, and body
      temperature, and alpha-BTX binding during and after CCS treatment. CCS treatment
      resulted in rapid decreases in sensitivity to nicotine for four of the five
      responses that were measured, as well as rapid changes in alpha-BTX binding.
      Sensitivity to nicotine returned to control levels within 3 days following pellet
      removal, but alpha-BTX binding returned to control levels in most brain regions 9
      11 days after pellet removal. Because the restoration of control sensitivity to
      nicotine occurred long before alpha-BTX binding returned to control levels, it
      seems likely that factors other than changes in alpha-BTX binding cause chronic
      CCS-induced changes in sensitivity to nicotine.

PMID- 8545486
TI  - Effect of chronic piracetam on age-related changes of cross-maze exploration in
      mice.
AB  - Normal aging is known to deteriorate memory, spatial orientation, and perceptual
      recognition. Experiment 1 examined behavioral manifestations of aging by using a
      cross-maze exploration test in 2-, 6-, and 10-month-old hybrid mice (CBA x
      C57BL). A decrease in explorative patrolling and an increase in arm reentries, a
      latency to start and a total time of exploration were found in 10-month-old mice.
      In Experiment 2, administration of the cognition enhancer piracetam (2-oxo-1
      pirrolidone acetamide) (400 mg/kg, IP, once a day for 10 days) enhanced arm
      patrolling and decreased reentries in 10-month-old mice to the level displayed by
      the 2-month-old animals. The results suggest that the cross-maze test may be
      useful for a preliminary screening of antisenescent drugs.

PMID- 8545487
TI  - An attempt to attenuate experimental pain in humans by dextromethorphan, an NMDA
      receptor antagonist.
AB  - Dextromethorphan (100 mg, orally), an NMDA receptor antagonist, did not
      significantly attenuate pain intensity or unpleasantness induced by experimental
      ischemia or by topical capsaicin in healthy human subjects, nor did it increase
      the threshold for heat pain or mechanical pain. A dose of 200 mg produced marked
      side effects. Thus, systemically administered dextromethorphan does not attenuate
      pain at clinically applicable doses in humans.

PMID- 8545488
TI  - Phencyclidine impairs temporal order memory for spatial locations in rats.
AB  - The effects of phencyclidine (PCP), an NMDA antagonist, was assessed on a complex
      task that has been shown to be dependent on hippocampal function. This task
      required memory for the temporal order of spatial locations. Rats were given IP
      injections of saline or PCP (3-4 mg/kg) on a double alternation schedule. With
      PCP injections rats were severely impaired relative to saline injections.
      Furthermore, PCP was shown to have no effects on the ability of rats to
      discriminate three-dimensional objects (a task that is not dependent on
      hippocampal function). The present data, in conjunction with previous results,
      suggest that the involvement of NMDA receptors in the hippocampus might be a
      function of the complexity of the task.

PMID- 8545489
TI  - Physical therapists' recognition of battered women in clinical settings.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to describe physical
      therapists' knowledge regarding battered women and to determine whether physical
      therapists recognize these patients in clinical settings. SUBJECTS AND METHODS:
      Two hundred questionnaires were distributed to outpatient physical therapists in
      northern California. One hundred fifty-one usable questionnaires (76%) were
      returned. RESULTS: Although 43% of the respondents reported treating a patient
      they identified or strongly suspected as having been battered, only two
      respondents (1%) reported they routinely asked patients about physical abuse.
      Less than 50% of the respondents correctly identified that battering injuries are
      more likely to occur in a central pattern (ie, head, neck, chest, abdomen).
      DISCUSSION AND CONCLUSION: The results of this survey suggest that physical
      therapists have treated patients who are battered. Many physical therapists,
      however, may not be fully educated to detect the signs of abuse. This study is
      the first step in initiating physical therapy research in domestic violence
      identification and education.

PMID- 8545490
TI  - Clinical decision making by experienced and inexperienced pediatric physical
      therapists for children with diplegic cerebral palsy.
AB  - BACKGROUND AND PURPOSE: This qualitative study was designed to explore, identify,
      and describe clinical decision-making processes used by pediatric physical
      therapists. SUBJECTS: Clinical decision-making processes of three experienced
      therapists and three inexperienced therapists were assessed as they worked with
      18 children with diplegia. METHODS: Retrospective think-aloud procedures were
      used to elicit verbalizations, which were transcribed, coded, and analyzed.
      RESULTS: Four characteristics of clinical decision making were identified: (1)
      Movement scripts provided insights into the clinical application of cognitive
      schemata based on previous experiences, (2) procedural changes occurred rapidly
      during within-session decision making, (3) psychosocial sensitivity was important
      for positive interaction during therapy, and (4) self-monitoring appeared to be
      pivotal in making clinical decisions as therapists self-assessed their practice.
      Contrasting data illustrated similarities and differences of experienced and
      inexperienced clinicians. CONCLUSION AND DISCUSSION: Findings are generally
      consistent with existing clinical decision-making literature and provide
      important information for physical therapy practice, research, and education.

PMID- 8545491
TI  - Cardiovascular and metabolic responses to upper- and lower-extremity exercise in
      men with idiopathic Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: The aerobic capacity of individuals with Parkinson's
      disease (PD) has not been characterized. This study (1) compared maximal exercise
      performance in individuals with and without PD, (2) compared exercise performance
      during upper- and lower-extremity exercise, and (3) described submaximal exercise
      responses. SUBJECTS: Eight men with PD (PD group) and 7 men without PD (control
      group) participated. METHODS: Subjects performed a lower-extremity ergometer test
      (LE test) and an arm-cranking ergometer test (AC test). Peak oxygen consumption,
      heart rate, respiratory exchange ratio, and power, as well as submaximal values
      of oxygen consumption and heart rate for each power level, were recorded.
      RESULTS: No differences were found between the groups for either test. Peak power
      was less for the PD group than for the control group for both tests. Submaximal
      heart rate and oxygen consumption were higher for the PD group than for the
      control group. CONCLUSION AND DISCUSSION: We conclude that individuals with mild
      to moderate PD can be tested with both exercise protocols to a peak exercise
      capacity and that there are differences in upper- and lower-extremity peak power
      and submaximal responses between persons with and without PD.

PMID- 8545492
TI  - A comparison of pisiform and thumb grips in stiffness assessment.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether two
      versions of the posteroanterior (PA) pressure test provide similar stiffness
      information. SUBJECTS: Twenty subjects were asked to judge the magnitude of five
      stiffness stimuli provided by a mechanical device. METHODS: Subjects were
      required to rate the stiffness magnitude on a five-point scale using both the
      thumb-grip and pisiform-grip versions of the PA pressure test. Using signal
      detection theory methods, measures of both a subject's ability to discriminate
      between the stiffness stimuli and a subject's bias in perceived stiffness
      magnitude due to the testing method were obtained. These values were compared
      using analysis of trend within an analysis of variance framework. RESULTS: The
      two methods of performing the PA central pressure had similar stimulus
      discriminability. With the thumb-grip method, however, a substantial bias
      occurred, making the mechanical stimuli appear to be stiffer than when the
      pisiform grip was used. CONCLUSION AND DISCUSSION: The method of performing the
      PA central pressure test affects the perceived magnitude of stiffness stimuli.
      This results suggests that the two versions of this clinical test should not be
      used interchangeably.

PMID- 8545493
TI  - Responses within nonfederal hospitals in Pennsylvania to the Americans with
      Disabilities Act of 1990.
AB  - BACKGROUND AND PURPOSE: This study described responses within nonfederal
      hospitals in Pennsylvania to the Americans With Disabilities Act of 1990 (ADA).
      SUBJECTS: The target population consisted of all 277 nonfederal hospitals
      licensed by the Pennsylvania Department of Health and Department of Public
      Welfare. METHODS: Questionnaires were mailed to the 270 chief administrators for
      the 277 hospitals. RESULTS: One hundred seventeen questionnaires (43.3%) were
      returned. More facilities had trained their managers regarding the ADA versus
      their nonmanagerial employees. Overall, 80.3% of the hospitals had an ADA
      committee or coordinator. Fifty-four percent of the respondents reported that job
      accommodations cost less than $500. Approximately 45% of the participants cited
      that the percentage of new construction costs spent to increase accessibility in
      their hospitals was less than 4.9%. More complaints and legal matters were
      received by facilities regarding the employment provisions of the ADA rather than
      the accessibility provisions. CONCLUSION AND DISCUSSION: The results suggest that
      hospitals need to monitor ADA-related expenses, more employee training is needed
      to ensure the ADA's success, and more representation is needed on hospital
      committees by rehabilitation personnel and individuals with disabilities.

PMID- 8545494
TI  - Management of a patient with lacerations of the tendons of the extensor digitorum
      and extensor indicis muscles to the index finger.
AB  - The purpose of this report is to describe the management of a 30-year-old male
      truck driver following a zone-VI (metacarpal level) laceration of the tendons of
      the extensor digitorum and extensor indicis muscles to the index finger. Surgical
      repair was performed 6 days after the injury and was followed by a 32-day period
      of short-arm cast immobilization. Physical therapy was begun immediately
      following cast removal. At about 8 to 10 days into the rehabilitation process, we
      became concerned about an increasing extensor lag (active extension less than
      passive extension), which affected the treatment program. We hypothesized that
      the scar at the tendon repair site had become excessively lengthened, and we
      therefore discontinued all flexion stretching and emphasized active extension.
      Additionally, we rested the joint in extension using a static splint except
      during exercise. As the patient's extensor lag improved, we increased the vigor
      of active extension exercise to promote tendon gliding and elongate restricting
      adhesions. The patient regained full range of motion and was able to return to
      work at full duty. The immobilization period implemented postoperatively in this
      case represents a traditional, conservative approach. The case emphasizes the
      need for careful monitoring and interpretation of both active and passive range
      of motion following tendon repair.

PMID- 8545495
TI  - Identifying patients with diabetes mellitus who are at risk for lower-extremity
      complications: use of Semmes-Weinstein monofilaments.
AB  - Research indicates that the SW monofilament is an inexpensive, reliable, valid,
      and easy-to-use clinical indicator for identifying patients who are at risk for
      developing foot ulcers and subsequent amputations. Those patients unable to sense
      the 5.07 SW monofilament on any part of their foot should be provided preventive
      care, including patient education and prescription of appropriate therapeutic
      footwear.

PMID- 8545496
TI  - Dangers in extrapolating in vitro uses of therapeutic ultrasound.

PMID- 8545497
TI  - Structural differences in the cerebral cortex of healthy female and male
      subjects: a magnetic resonance imaging study.
AB  - There are both reproductive and nonreproductive behavioral differences between
      men and women. Brain regions involved in determining sexual behavior have been
      reported to differ between the sexes. Nonreproductive, cognitive functional
      differences between sexes might be reflected in higher-order cortical structural
      dimorphisms, which have not previously been studied. We hypothesized that
      cortical regions involved in verbal behavior (which is sexually dimorphic) would
      differ between sexes. Using magnetic resonance imaging, we assessed gray matter
      volumes in several cortical regions in 17 women and 43 men. Women had 23.2%
      (dorsolateral prefrontal cortex) and 12.8% (superior temporal gyrus) greater gray
      matter percentages (corrected for overall brain size and age) than men in a
      language-related cortical region, but not in a more visuospatially related
      cortical region. These data seem to establish sexually dimorphic structural
      differences in the cerebral cortex, consistent with prior cerebral blood flow
      reports.

PMID- 8545498
TI  - Asymmetry of the planum temporale: methodological considerations and clinical
      associations.
AB  - Asymmetry of the planum temporale, a region on the posterosuperior surface of the
      temporal lobe involved in the production and comprehension of language, is a
      notable feature of the normal human brain. Several attempts have been made to
      measure it using both post-mortem and magnetic resonance imaging (MRI) methods,
      but previous approaches made inadequate allowance for the convoluted nature of
      the structure. The current study used rigorous criteria to define the planum and
      examined three separate approaches for its measurement on MRI scans. A method
      involving triangulation of the surface consistently gave larger values for the
      surface area of the planum, suggesting that this method takes account of the
      convoluted nature of the structure.

PMID- 8545499
TI  - Lateralized abnormality of high-energy phosphate and bilateral reduction of
      phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the
      frontal lobes in schizophrenia.
AB  - Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used
      to measure membrane phospholipid metabolism and high-energy phosphate metabolism
      in the left and right frontal lobes of 27 schizophrenic patients. In the
      schizophrenic patients, the phosphomonoester peak area was decreased in bilateral
      frontal lobes compared with that in age-matched normal subjects. On the other
      hand, the peak area of beta-adenosine triphosphate was increased in the left
      frontal lobe in the schizophrenic group. The phosphocreatine peak area was
      increased in the left frontal lobe of schizophrenic patients with high scores on
      the Scale for the Assessment of Negative Symptoms (SANS).

PMID- 8545500
TI  - Altered frontostriatal relationship in unmedicated schizophrenic patients.
AB  - Positron emission tomography with [18F]-fluoro-2-deoxy-D-glucose as tracer was
      used to investigate frontal glucose metabolism in 15 unmedicated schizophrenic
      patients and 15 healthy subjects under resting conditions. Although no difference
      in absolute frontal cerebral metabolic rates of glucose (CMRglu) were found
      between schizophrenic patients and control subjects, relative measures
      significantly differentiated the two groups. Whole frontal metabolism and
      frontocaudate ratio were significantly decreased in both hemispheres in the
      patients. The results confirm the existence of hypofrontality in unmedicated
      schizophrenia and indicate disturbances in metabolic relationships between the
      frontal cortex and the striatum in this disorder.

PMID- 8545501
TI  - Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism.
AB  - In an attempt to elucidate the physiological basis of hypnosis, we investigated
      the changes of whole-brain and regional cerebral glucose metabolism, from a state
      of resting wakefulness to a hypnotized state with whole-body catalepsy, using
      positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly
      hypnotizable adults. Neither the random order of study conditions nor any of the
      other experimental factors had a measurable effect, and there was no
      statistically significant global activation or metabolic depression. However,
      repeated measures analysis of variance revealed a statistically significant
      heterogeneity of symmetric regional responses: Mainly the occipital areas,
      including visual and paravisual cortex, became relatively deactivated, while some
      metabolic recruitment was found in structures involved in sensorimotor functions.
      The observed pattern of changes of regional cerebral activity corresponds with
      the shift of attention away from normal sensory input that hypnosis is known to
      produce.

PMID- 8545502
TI  - Single-word auditory stimulation and regional cerebral blood flow as studied by
      SPECT.
AB  - Single photon emission computed tomography (SPECT) examined changes in regional
      cerebral blood flow (rCBF) induced by passive auditory single-word stimulation. A
      split-dose SPECT technique was used between resting and activated states, in
      which a smaller amount of ligand (99m technetium hexamethyl propyleneamine oxide,
      HMPAO) was given with the first scan, accompanied by a prolonged scan time. A
      larger amount of ligand was given with the second scan, accompanied by a shorter
      scan time. This split-dose SPECT technique has met with previous success for
      other activation tasks. The brain regions of interest (ROIs) in this study were
      selected from ROIs previously found to be activated by passive auditory single
      word stimulation and not by non-word stimuli in positron emission tomography
      (PET) rCBF studies. This study thus tested the sensitivity of SPECT with HMPAO to
      detect brain activation with a stimulus previously demonstrated to elicit changes
      in rCBF with PET. However, no significant difference was detected between resting
      and activated states in this study. Thus, SPECT was not as sensitive as PET in
      this activation task. Since SPECT is a less costly and more widely available
      modality to study brain activation than PET, it is important to delineate its
      potential capacities to maximize the efficiency of future research in this field.

PMID- 8545503
TI  - Searching for common ground: the new pluralism.

PMID- 8545504
TI  - Rachel T.: an adolescent treatment case.

PMID- 8545505
TI  - A Freudian perspective on Rachel's struggle.

PMID- 8545506
TI  - A relational perspective on Rachel's struggle.

PMID- 8545507
TI  - In the shadow of death.
AB  - Death dogged Vincent's footsteps throughout his life, and formed a core component
      of his unconscious fantasy system. It cast a lugubrious shadow over all of his
      undertakings--he found little joy and less love in life. It found its way onto
      his canvases, both directly--the grinning death's head--and indirectly. It found
      expression in his portrayals of sowers and reapers, in his representations of
      trees--especially the highly symbolic treatments of cypresses--in the menacing
      crows hovering over storm-darkened fields of wheat, and finally in the images of
      Christ, suffering and dead, held in the embrace of a loving and grieving mother.
      If death was a bottomless pit that haunted him with its terrors, it was also a
      siren song that drew him ever closer to his destiny, ever closer to the edge of
      the pit. The power of that attraction lies in his identification with the dead
      Vincent whose place he had taken and whose name he bore. It was through that
      identification, and through the passageway of suffering and death that he would
      surcease in the arms of a loving and accepting mother whose warm embrace he had
      sought throughout his odyssey, but in vain. It was to be gained only in and
      through death. It was only through death that he would find rest from his pain
      and would gain the heavenly reward of his suffering in eternal love and bliss.

PMID- 8545508
TI  - Beyond sublimation: the nature of optimal psychodynamic conflict resolutions.

PMID- 8545509
TI  - The vital role of adaptive grandiosity in artistic creativity.
AB  - The artist needs adaptive grandiosity in order to create. Adaptive grandiosity is
      an ego-state that derives from primary narcissism and a partial resolution of the
      positive Oedipus complex, with the ego-ideal merged with the ego. It functions as
      a manic defense to overcome the artist's annihilation anxiety when confronting
      the blank canvas or other aspects of creativity which unconsciously represent
      separation from the maternal introject. Because of it fragile, defensive nature,
      adaptive grandiosity can readily degenerate into maladaptive grandiosity
      (omnipotence), which can block creativity. Clinical examples are used to
      illustrate the differences between adaptive grandiosity and omnipotence.

PMID- 8545511
TI  - Lacanian perspectives on political and social controversies: a symposium.

PMID- 8545510
TI  - The tragic actor: forms and transformations of narcissism in the life and work of
      Edouard Manet (1832-1883).
AB  - This paper has explored some of the developmental factors and psychological
      conflicts that may have played a central role in the life of the French artistic
      revolutionary, Edouard Manet. A case is made that Manet suffered from a
      narcissistic personality disturbance based on considerable, albeit spurious,
      individuation in the face of failed separation. Preoedipal and oedipal conflicts
      are traced from the available biographical data. They suggest that Manet's
      lifelong yearning for approbation and inability to sustain mature object
      relationships derived from his quest for a loving, admiring father and a struggle
      against an enveloping, rejecting mother. Failed paternal identifications,
      persistent primal maternal identifications, excessive needs for selfobject
      affirmation, superficial but compulsive heterosexuality, and rejection of his own
      paternity appear to have been powerful forces within Manet that found expression
      in his life and creative products. Although painting enabled Manet to transcend
      some of his own characterological vulnerabilities, he remained a tormented
      personality quite destructive towards others and to himself. Understanding more
      fully the developmental impingements and facilitators of this "tragic actor"
      helps his audience gain a greater appreciation of his artistic contribution.

PMID- 8545512
TI  - Doctor-assisted suicide: psychoanalysis of mass anxiety.

PMID- 8545513
TI  - Sexuality and the law: a Lacanian examination of date rape.

PMID- 8545514
TI  - Lacan and the critique of legal ideology: reason and religion in law and
      politics.

PMID- 8545516
TI  - Ulysses and I: a brief memoir of a long analysis.

PMID- 8545515
TI  - When the patient is a therapist: special challenges in the psychoanalysis of
      mental health professionals.

PMID- 8545517
TI  - Close Encounters: unidentified flying object relations.

PMID- 8545518
TI  - An effect of triazolam on visual attention and information processing.
AB  - This study explored whether benzodiazepines selectively affect aspects of
      attention and/or visual information processing, as they do memory. A cued visual
      search paradigm was employed, using normal volunteers and a single dose of
      triazolam. This paradigm provided for a detailed examination of two aspects of
      visual attention and information processing: 1) controlled versus automatic
      attention allocation (via central and peripheral cues), and 2) the extent to
      which processing an item in a non-cued location affects performance (via cue
      validity). Triazolam, compared to placebo, significantly increased response time,
      and Drug Condition interacted with Cue-Validity but not Cue-Type. Based on these
      data, we argue that triazolam does not affect attention allocation but does
      affect attentional disengagement and/or attention switching mechanisms.

PMID- 8545519
TI  - Food deprivation affects extinction and reinstatement of responding in rats.
AB  - Food deprivation has been shown to increase the self-administration of a wide
      variety of drugs in a number of different species. However, the effects of food
      deprivation on other phases of drug taking have not been established. The purpose
      of the present study was to evaluate the effects of food deprivation on
      reinstatement of responding for cocaine. Rats trained to self-administer 0.2,
      0.4, or 1.0 mg/kg cocaine intravenously (IV) under a fixed-ratio 1 schedule for
      the first 2 h during daily 7-h sessions were fed either before or after the
      experimental session. During hours 3-7, rats self-administered saline. Saline
      replaced cocaine in the infusion pumps at the beginning of hour 3 and a priming
      injection of either saline or cocaine (0.32, 1.0, or 3.2 mg/kg IV) was
      administered at the beginning of hour 4. The number of infusions that was self
      administered was measured throughout the 7-h session. During hours 1 and 2 when
      cocaine was available, the number of infusions was inversely related to cocaine
      dose. During hour 3, rats typically self-administered several infusions of
      saline, which gradually decreased to near-zero levels by hours 4-7 (extinction
      responding). A priming injection of cocaine administered at the beginning of hour
      4 reinstated responding in a dose-related manner. The magnitude of extinction
      responding during hour 3 and reinstatement of responding during hour 4 were
      similar regardless of cocaine maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545520
TI  - Scopolamine prevents augmentation of stereotypy induced by chronic
      methamphetamine treatment.
AB  - Cholinergic neurotransmission has been implicated in various forms of neural
      plasticity such as kindling and learning. We have previously shown that blockade
      of muscarinic cholinergic receptors prevents the development of locomotor
      sensitization to methamphetamine. The present study was conducted to examine
      whether scopolamine, a muscarinic cholinergic antagonist, would also block
      augmentation of stereotypy induced by chronic methamphetamine (MA) treatment.
      Rats treated with MA (2.5 mg/kg, SC) for 10 days indicated significantly enhanced
      stereotyped behavior when tested with MA (2.5 mg/kg) after a 7- to 8- day
      withdrawal. Pretreatment with scopolamine (3 mg/kg) prior to MA administration
      prevented the augmentation of stereotypy. Rats treated with scopolamine alone
      showed no difference in MA-induced stereotypy compared to those treated with
      saline. Scopolamine methylbromide, a derivative of scopolamine that does not
      easily cross the blood-brain barrier, had no effect on the augmentation of
      stereotypy. These results suggest that stimulation of central muscarinic
      cholinergic receptors plays a role in the development of sensitization to the
      stereotypy stimulating effect of methamphetamine.

PMID- 8545521
TI  - Cholinergic modulation of a decrement in social investigation following repeated
      contacts between mice.
AB  - Social recognition has been inferred from a decline in olfactory investigation of
      conspecific intruders during repeated or protracted confrontation with a resident
      rat. A stimulus-response relationship defined by lack of response remains
      somewhat ambiguous. Since it is likely that behavior continues to be emitted by
      the resident animal, how behavior reorganizes as the resident becomes familiar
      with an intruder represents an important issue in the characterization of
      recognition. We examined the decline in olfactory investigation of ovariectomized
      females by adult male mice. The duration and frequency of olfactory investigation
      was measured during four 1 minute confrontations with 10-min intertrial intervals
      (Training trials). If the same female was presented in each trial, investigation
      declined to less than 50% of initial levels. Aggressive behavior gradually
      increased with repeated trials. No decline in investigation or increased
      aggression was measured when females were changed in each trial. Administration
      of doses of scopolamine (0.16-1.0 mg/kg, IP) blocked decrements in olfactory
      investigation in repeated confrontations and significantly reduced aggression. Co
      administration of heptylphysostigmine (0.32-5.0 mg/kg, IP) reversed scopolamine's
      effects on olfactory investigation but not aggression. Acetylcholinesterase
      inhibitors heptylphysostigmine, galanthamine (0.63-2.5 mg/kg, IP) and tacrine
      (0.63-10.0 mg/kg, IP) all enhanced the rate of decrement of olfactory
      investigation when administered alone, but had differential effects on
      aggression. The decline in investigation corresponds to criteria for habituation.
      Increased responsivity expressed as aggression indicates recognition may also be
      characterized as a change in behavioral strategy dependent on the sexual and
      social status of the stimulus animal. Pharmacological data support a role for
      acetylcholine release in the development of social recognition as an olfactory
      memory, or through modulation of olfactory perception.

PMID- 8545522
TI  - The additive effects of quinine on antidepressant drugs in the forced swimming
      test in mice.
AB  - The aim of this study was to investigate if quinine plus antidepressant drugs
      (ADS) leads to an additive effect in the forced swimming test. Quinine (0.125,
      0.5 mg/kg) and ADS (subactive doses) were given IP 45 and 30 min, respectively,
      before the test. When combined with QUIN, all drugs that act via inhibition of 5
      HT uptake (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine and
      fluvoxamine) significantly increased the swimming time of mice. Among trazodone,
      mianserin and iprindole (atypical ADS), only iprindole combined with quinine
      decreased the immobility (increased swimming) of the animals. The specific
      noradrenaline (NA) uptake inhibitors, desipramine and viloxazine, but not
      maprotiline, were also found to reduce the immobility time when pretreated with
      quinine. The mixed monoamine oxidase (MAO) inhibitor (pargyline) and MAO-A
      inhibitor (moclobemide) also shortened the period of immobility whereas the MAO-B
      inhibitor (nialamide) and the dopamine (DA) uptake inhibitor (bupropion) did not.
      Quinine's additive effects on several types of ADS is likely a result of blockade
      of potassium channels.

PMID- 8545523
TI  - Enhancement of acetylcholine release by flumazenil in the hippocampus of rats
      chronically treated with diazepam but not with imidazenil or abecarnil.
AB  - The effects of long-term treatment (three times a day for 3 weeks) with
      pharmacologically active doses of the novel anxiolytics and anticovulsants
      abecarnil (0.5 mg/kg, IP) and imidazenil (0.5 mg/kg, IP) on basal hippocampal
      acetylcholine release in freely moving rats were compared with those of diazepam
      (3 mg/kg, IP). Challenge doses of diazepam, abecarnil, and imidazenil decreased
      the extracellular acetyl-choline concentration in the hippocampus by the same
      extent in animals chronically treated with the respective drug or vehicle.
      Moreover, the abrupt discontinuation of long-term treatment with diazepam,
      abecarnil, or imidazenil failed to affect hippocampal acetylcholine release
      during the first 5 days of withdrawal. In contrast, the acute administration of
      the benzodiazepine receptor antagonist flumazenil (1 mg/kg, IP) 2 days after
      diazepam withdrawal elicited a marked increase (65%) in acetylcholine release in
      the hippocampus. Flumazenil failed to induce the same effect 5 days after
      diazepam withdrawal or 2 or 5 days after discontinuation of long-term treatment
      with abecarnil or imidazenil. These results indicate that (i) the inhibitory
      effects of full (diazepam), partial (imidazenil), and selective (abecarnil)
      benzodiazepine receptor agonists on acetylcholine output in rat hippocampus are
      not affected by repeated drug administration; (ii) discontinuation of long-term
      treatment with each type of agonist does not affect hippocampal cholinergic
      mechanisms; and (iii) flumazenil increases acetylcholine release only in the
      hippocampus of rats chronically treated with diazepam. Together, these data
      further differentiate the pharmacology of benzodiazepine receptor full agonists
      from that of partial and selective agonists.

PMID- 8545524
TI  - The anxiolytic-like activity of GR159897, a non-peptide NK2 receptor antagonist,
      in rodent and primate models of anxiety.
AB  - The non-peptide NK2 receptor antagonist, GR159897, was evaluated in two putative
      models of anxiety, the mouse light-dark box and the marmoset human intruder
      response test. Effects were compared to the structurally dissimilar NK2
      antagonist, (+/-) SR48968 and the benzodiazepines, diazepam and chlordiazepoxide.
      GR159897 (0.0005-50 micrograms/kg SC) caused significant and dose-dependent
      increases in the amount of time mice spent in the more aversive light compartment
      of the light-dark box, with no effect on locomotor activity. (+/-)SR48968 (0.0005
      0.5 microgram/kg SC) and diazepam (1-1.75 mg/kg SC), also increased time spent in
      the light compartment, without effect on locomotor activity. In the marmoset
      human intruder response test, GR159897 (0.2-50 micrograms/kg SC) significantly
      increased the amount of time marmosets spent at the front of the cage during
      confrontation with a human observer ("threat"). Similar effects were produced by
      (+/-)SR48968 (10-50 micrograms/kg SC) and chlordiazepoxide (0.3-3.0 mg/kg SC).
      These results provide further evidence, in both rodent and primate species, for
      the ability of NK2 antagonists to restore behaviours which have been suppressed
      by novel aversive environments. Such effects indicate that NK2 antagonists may
      have anxiolytic activity.

PMID- 8545525
TI  - Ro 15-4513 selectively attenuates ethanol, but not sucrose, reinforced responding
      in a concurrent access procedure; comparison to other drugs.
AB  - The experiments described in this report used a concurrent access procedure to
      study ethanol reinforcement. Rats were trained to lever press for a 10% sucrose
      solution and a 10% ethanol/10% sucrose mixture, and both reinforcers were
      available on variable-interval 5-s schedules. In baseline and vehicle injection
      sessions, the animals distributed their responding between both solutions. When
      injected with the partial inverse benzodiazepine agonist Ro 15-4513 (3, 9, and 18
      mg/kg), responding for the ethanol solution decreased while responding for
      sucrose remained intact. Ethanol injections (0.5 and 1.0 g/kg) engendered a
      similar profile. Chlordiazepoxide led to an increase in ethanol mix responding at
      2 mg/kg and a decrease in ethanol mix responding at higher doses; no dose
      affected sucrose responding. Morphine (0.5-16 mg/kg) decreased responding for
      both the ethanol mix and sucrose solutions, more or less simultaneously. Naloxone
      (0.125-20 mg/kg) selectively reduced ethanol mix responding at low doses, and
      decreased responding for both reinforcers at high doses. In another group of
      animals, isocaloric alternatives were concurrently available: 10% ethanol/0.25%
      saccharin versus 14% sucrose. Injections of Ro 15-4513 and chloridiazepoxide
      produced similar results as in the first group of rats: an increase in ethanol
      mix responding with low dose chlordizepoxide, and a decrease in ethanol mix
      responding with Ro 15-4513. However, naloxone injections did not selectively
      affect responding for either of the reinforcers when they were isocaloric. These
      results are discussed in terms of ethanol's neuropharmacological actions.

PMID- 8545526
TI  - Delta opioid receptors: reflexive, defensive and vocal affective responses in
      female rats.
AB  - Ultrasonic vocalizations may be an expression of the affective pain response in
      laboratory animals. The present experiment compares the effects of morphine to
      the delta agonist, DPDPE (D-Pen2,D-Pen5 enkephalin) on a range of reflexive,
      behavioral and affective responses during an aggressive interaction. In
      experiment 1, naive female Long-Evans rats received morphine (0, 1, 3, 6, 10
      micrograms ICV), or DPDPE (0, 30, 60, 100 micrograms ICV). In experiment 2,
      female rats were treated with naltrindole (1.0 mg/kg IP) 20 min before DPDPE (0,
      60, 100 micrograms ICV). The following endpoints were measured: (1) latency to
      tail flick in response to heat stimuli; (2) high (33-65 kHz) and low (20-32 kHz)
      frequency ultrasonic and audible vocalizations; (3) defensive behavior; and (4)
      motoric activity. Following a brief exposure to attack, rats were threatened by
      the aggressor but protected from further attack by a large, wire mesh cage,
      thereby allowing for continued behavioral and vocal measurement without the risk
      of physical injury; video and audio recordings were made during the attack and
      then during a portion of the protected encounter (2 min). Morphine suppressed
      pain reactions varying in complexity from a spinal reflex, to an organized escape
      reaction, to an affective vocal response. The delta agonist, DPDPE, attenuated
      high frequency ultrasonic calling and tail flick responding. Defensive behaviors
      were also modulated by DPDPE at doses that had no effect on walking or rearing,
      indicating behavioral specificity. By contrast, doses of morphine that decreased
      defensive upright and escape also decreased motor activity. In female rats,
      morphine and DPDPE share a common profile of effects on a range of functional end
      points, but DPDPE appears to modulate more selectively the reactions related to
      aversiveness without exerting sedative effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545527
TI  - Significance of adrenal corticosteroid secretion for the food restriction-induced
      enhancement of alcohol drinking in the rat.
AB  - Male Wistar rats with continuous access to 6% ethanol solution and water in their
      home cages were subjected to food restriction (FR). Reduction of body weight to
      80% of normal was associated with a significant increase in ethanol drinking. It
      is known that the stress of FR gives rise to increased corticosterone secretion,
      and in line with these findings it was found that the weight of the thymus (whose
      size is inversely related to corticosterone levels) was reduced to 55% of normal
      in the present FR rats. Two subsequent experiments indicated that this adrenal
      activation contributed to the FR-induced enhancement of alcohol drinking.
      Firstly, adrenalectomized rats showed no evidence of enhanced alcohol drinking
      during food restriction, suggesting that adrenal corticosterone hypersecretion
      contributes to the enhanced ethanol consumption during FR. Secondly, treatment of
      FR rats with the enzyme inhibitor cyanoketone, which blocks stress-induced but
      not basal corticosterone secretion, at least partly prevented the FR-induced
      increase in ethanol drinking. These results add further evidence that sustained
      exposure to corticosterone facilitates ethanol consumption in the rat.

PMID- 8545528
TI  - Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion
      on focused attention and attentional search.
AB  - As the catecholamines have long been implicated in attentional processes, the
      present investigation compared the effects of the mixed alpha 1/alpha 2
      adrenoceptor agonist clonidine (CLO), the benzodiazepine diazepam (DZP), the
      D1/D2 antagonist haloperidol (HAL) and a low-tryptophan drink (Lo-TRP) on
      performance of tests of selective attention with distractors in four groups of
      young, healthy volunteers. Using a placebo-controlled, cross-over design,
      selective and dissociable effects on performance were found with each
      pharmacological manipulation. Specifically, CLO acted to broaden the focus of
      attention, HAL generally slowed reaction times during attentional search, and DZP
      and Lo-TRP produced differential effects on stimulus-response compatibility
      during attentional search. Furthermore, these results underline the usefulness of
      employing a single test with several neurochemical manipulations, allowing for a
      comprehensive analysis of the neurochemical basis of attention.

PMID- 8545529
TI  - Differential cholinergic regulation in Alzheimer's patients compared to controls
      following chronic blockade with scopolamine: a SPECT study.
AB  - The effects of low-dose chronic scopolamine on measures of cerebral perfusion and
      muscarinic receptors were tested in eight Alzheimer's disease (AD) subjects and
      eight elderly controls. Single photon emission computed tomography (SPECT) scans
      using technetium-labelled hexamethypropylene amine oxide (99mTc-HMPAO) to measure
      cerebral perfusion before and after chronic scopolamine revealed a significant
      12% increase in the normal controls (P < 0.01) while the AD subjects showed no
      significant change. In contrast, the controls showed decreased muscarinic binding
      as evidenced by 123I-quinuclidinyl-4-iodobenzilate (123I-QNB) labelling after
      chronic drug (-10%, P < 0.01) whereas the AD subjects showed increased 123I-QNB
      labelling (+8%, P < 0.05). The difference between AD and control subjects was
      even more marked when the ratio of I-QNB to HMPAO uptake was compared, pointing
      to a double dissociation in the SPECT results. These data cannot be explained by
      group differences in cerebral perfusion alone and suggest a differential
      sensitivity between AD and elderly controls to chronic cholinergic blockade.

PMID- 8545530
TI  - Reversal of triazolam- and zolpidem-induced memory impairment by flumazenil.
AB  - The effects of flumazenil, a benzodiazepine receptor antagonist, on triazolam-
      and zolpidem-induced memory impairment were investigated. Sixty subjects received
      oral triazolam 0.5 mg, zolpidem 20.0 mg, or placebo at 10 a.m. (n = 20 per drug).
      Ninety minutes later, half of the subjects (n = 10) in each oral drug group were
      administered flumazenil 1.0 mg, while the remaining half received placebo (normal
      saline), through indwelling venous catheters. Learning/memory tests (including
      Simulated Escape, Restricted Reminding, Paired-Associates, and Repeated
      Acquisition) were administered at that time, and at 1.5-h intervals over the next
      6 h. Triazolam/placebo and zolpidem/placebo drug combinations impaired memory on
      all tests (all Ps < 0.05). However, the triazolam/flumazenil and
      zolpidem/flumazenil groups showed no evidence of impairment during any test
      session. These results demonstrate that flumazenil 1.0 mg rapidly and lastingly
      reverses memory impairment caused by agonists of the benzodiazepine receptor.
      Furthermore, nonsignificant trends suggested that performance of the
      placebo/flumazenil group was consistently better than that of the placebo/placebo
      group, denoting a possible role of endogenous benzodiazepine agonists in natural
      sleep/wake processes.

PMID- 8545532
TI  - Oral movement patterns induced in rats by local infusions into striatum depend
      upon the regimen of prior neuroleptic exposure.
AB  - Rats were pretreated for 11 months with vehicle or with chronic haloperidol
      (HAL), administered either continuously (in the drinking water) or intermittently
      (via weekly injections). During this time the animals were habituated to an
      enclosed tube and periodically monitored by a computerized video device which
      measured their oral movements. The rats were then withdrawn from chronic HAL and
      bilateral cannulae were implanted in the ventrolateral striatum (VLS) and
      substantia nigra (SN). One week later oral movements were observed in an open
      cage and then measured by the computerized video device following bilateral
      infusions into VLS of the muscarinic agonist pilocarpine or the dopamine D1
      agonist SKF38393, or following infusions of the GABA antagonist bicuculline into
      SN. Agonist infusions into VLS had different effects depending upon the prior
      regimen of chronic HAL. Infusions of pilocarpine into VLS led to an exaggeration
      of the distinctive oral movement form which follows continuous HAL but an
      attenuation of the different oral syndrome in the intermittent chronic HAL
      animals. Infusions of SKF38393 into VLS had similar, but considerably smaller
      effects. Infusions of bicuculline into SN did not induce either effect. These
      results indicate differences exist in either striatum or its output circuitry in
      the neurochemical mechanisms which mediate the different oral movement forms
      induced by different chronic neuroleptic regimens.

PMID- 8545531
TI  - The benzodiazepine receptor antagonists flumazenil and CGS8216 block the
      enhancement of fear conditioning and interference with escape behavior produced
      by inescapable shock.
AB  - Prior work has suggested that the mediation of the behavioral effects of
      inescapable shock (IS) might involve release of an endogenous beta-carboline-like
      ligand at the dorsal raphe nucleus (DRN) that binds to the benzodiazepine (BZ)
      recognition site on the GABAA complex, thereby disinhibiting the DRN. This was
      tested by microinjection of the BZ receptor antagonists flumazenil and CGS8216 in
      the region of the DRN, either before IS or before later behavioral testing. Both
      compounds blocked subsequent enhancement of fear conditioning and interference
      with shuttlebox escape when administered before IS, but had no effect when given
      before testing. In addition, flumazenil did not alter the behavior of escapably
      shocked subjects.

PMID- 8545534
TI  - Chronic administration of l-sulpiride at non-neuroleptic doses reduces the
      duration of immobility in experimental models of "depression-like" behavior.
AB  - It has been shown that long-term administration of l-sulpiride induces a down
      regulation of beta receptor-associated adenylate cyclase activity in the frontal
      cortex of rats, and adaptive response that is typically associated with the
      chronic administration of antidepressants. Here we show that in two animal models
      of "depression-like" behavior (forced swim in rats and tail suspension in mice),
      the long-term (21 days) administration of l-sulpiride at a non-neuroleptic dose
      (2 mg/kg IP twice a day) significantly decreases the duration of immobility, the
      effect being similar to that of desipramine (20 mg/kg IP). The same dose (2
      mg/kg) of l-sulpiride, acutely administered, has no effect at all. On the other
      hand, either chronic (21 days) or acute administration of neuroleptic doses of l
      sulpiride have an opposite effect, and indeed increase the duration of
      immobility. These results are an in vivo support to the in vitro findings
      suggesting that low doses of l-sulpiride may have antidepressant-like activity.

PMID- 8545533
TI  - Psychopharmacological analysis of implicit and explicit memory: a study with
      lorazepam and the benzodiazepine antagonist flumazenil.
AB  - Recent studies have suggested that the benzodiazepine (BZ) lorazepam (LZ) differs
      from other BZs in its impairing effects on implicit memory tasks. The present
      study was designed to assess whether this atypical effect withstood the
      experimental rigour of Schacter's retrieval intentionality criterion and further,
      whether it could be reversed by the BZ antagonist, flumazenil (FL). The separate
      and combined effects of LZ, FL and placebo (PL) were assessed on indices of
      memory, sedation, and attention in 48 healthy volunteers. LZ disrupted
      performance on both explicit and implicit memory tasks, induced motor sedation
      and impaired focussed attention. Fl attenuated LZ-induced attentional deficits
      but did not affect motor sedation. FL also attenuated LZ-induced impairment on
      the implicit retrieval task. On the explicit retrieval task FL attenuated LZ
      induced impairment for words which had been deeply processed at study but not
      words which had been shallowly processed. A subsequent recognition test showed LZ
      impaired recognition memory only when accompanied by recollective experience and
      flumazenil again attenuated this effect. FL itself lowered performance on several
      measures, reflecting intrinsic activity of this "antagonist". Assessment of the
      relationship between the mnestic and other effects of the drugs suggested that
      attentional effects contribute to, but do not explain, effects on implicit memory
      tasks. These results imply that the apparent atypical effects of LZ on implicit
      memory tasks are mediated by the same BZ receptor complex as mediates LZ's other
      effects.

PMID- 8545535
TI  - Nicotine reinforcement in rats with histories of cocaine self-administration.
AB  - Few reports have described conditions under which nicotine self-administration
      occurs in rats. In this study, rats which initially lever pressed for cocaine
      infusion (0.05 mg/kg) during 1 h experimental sessions continued to obtain
      similar infusion numbers when nicotine (0.03 mg/kg) was available. When saline
      was substituted for nicotine, infusions decreased from 11.8 +/- 4.5/h to 5.4 +/-
      1.1/h but returned to pre-saline levels when it was reintroduced (12.0 +/-
      5.4/h). These results indicate that nicotine can serve as a positive reinforcer
      for rats under the historical and schedule conditions described.

PMID- 8545536
TI  - The medicinal chemistry and therapeutic potentials of ligands of the histamine H3
      receptor.

PMID- 8545537
TI  - Serotonin uptake inhibitors: uses in clinical therapy and in laboratory research.
AB  - Fluoxetine, zimelidine, sertraline, paroxetine, fluvoxamine, indalpine and
      citalopram are the selective inhibitors of serotonin uptake that have been most
      widely studied. Some of these compounds are or have been used clinically in the
      treatment of mental depression, obsessive-compulsive disorder and bulimia, and
      therapeutic benefit has been claimed in additional diseases as well. By blocking
      the membrane uptake carrier which transports serotonin from the extracellular
      space to inside the serotonin nerve terminals, these compounds increase
      extracellular concentrations of serotonin and amplify signals sent by serotonin
      neurons. Because serotonin neurons are widespread in the central nervous system,
      the functional consequences of blocking serotonin uptake are diverse, but are
      generally subtle. Animals treated with serotonin uptake inhibitors look normal in
      gross appearance, but effects such as reduced aggressive behavior, decreased food
      intake and altered food selection, analgesia, anticonvulsant activity, endocrine
      changes and neurochemical changes have been demonstrated and characterized.
      Serotonin uptake inhibitors have helped in revealing some dynamics of serotonin
      neurons; for example, when uptake is inhibited and extracellular serotonin
      concentration increases, presynaptic as well as postsynaptic receptors for
      serotonin are activated to a greater degree. A consequence of increased
      activation of autoreceptors on serotonin cell bodies and nerve terminals is a
      reduction in firing of serotonin neurons and a decrease in serotonin synthesis
      and release. The result is a limit on the degree to which extracellular serotonin
      and serotonergic neurotransmission are increased.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8545538
TI  - Generation of new-lead structures in computer-aided drug design.

PMID- 8545539
TI  - Natriuretic hormones II.

PMID- 8545540
TI  - Recent developments in the chemotherapy of osteoporosis.

PMID- 8545541
TI  - Calmodulin: effects of cell stimuli and drugs on cellular activation.
AB  - The activity, localization and cellular content of CaM can be regulated by drugs,
      hormones and neurotransmitters. Regulation of physiological responses of CaM can
      depend upon local Ca(2+)-entry domains in the cells and phosphorylation of CaM
      target proteins, which would either decrease responsiveness of CaM target enzymes
      or increase CaM availability for binding to other target proteins. Despite the
      abundance of CaM in many cells, persistent cellular activation by a variety of
      substances can lead to an increase in CaM, reflected both in the nucleus and
      other cellular compartments. Increases in CaM-binding proteins can accompany
      stimuli-induced increases in CaM. A role for CaM in vesicular or protein
      transport, cell morphology, secretion and other cytoskeletal processes is
      emerging through its binding to cytoskeletal proteins and myosins in addition to
      the more often investigated activation of target enzymes. More complete knowledge
      of the physiological regulation of CaM can lead to a greater understanding of its
      role in physiological processes and ways to alter its actions through
      pharmacology.

PMID- 8545542
TI  - Recent advances in benzodiazepine receptor (BZR) binding studies.

PMID- 8545543
TI  - Neuropeptides as native immune modulators.

PMID- 8545544
TI  - The concept of trophic units in the central nervous system.
AB  - The present paper proposes that trophic interplay among cells may represent the
      final common pathway for both genetic and environmental influences, and hence new
      criteria for the understanding of central nervous system (CNS) connectivity can
      be suggested. In particular, trophic signals may make up the common "language"
      through which genetic and epigenetic influences mold the CNS during development
      and the adult life. Furthermore, it will put forward the hypothesis that the
      developmental trophic interplay among cells leads to the formation of trophic
      units in the adult brain. A trophic unit is defined as the smallest set of cells,
      within the CNS, which act in a complementary way to support each other's
      trophism. The trophic units consist of neurons, glial cells, blood vessels,
      extracellular matrix (ECM). In particular, ECM gives support to the thin
      elongated cell processes and gives rise to selective chemical bridges between
      cell surfaces or between cell surfaces and the extracellular milieu. The trophic
      unit is a plastic device that not only assures neuronal survival, but also
      operates to adapt neuronal networks to new tasks by controlling extension of
      neuronal processes, synapse turnover and ECM characteristics. These plastic
      responses depend on the interplay of all the elements that constitute the trophic
      units. The concept of trophic unit may help to understand some features of
      neurodegenerative diseases, for example, the clustering of tangles in the
      neocortex and in the entorhinal cortex of Alzheimer's patients [corrected].

PMID- 8545545
TI  - Functional characteristics of the midbrain periaqueductal gray.
AB  - The major functions of the midbrain periaqueductal gray (PAG), including pain and
      analgesia, fear and anxiety, vocalization, lordosis and cardiovascular control
      are considered in this review article. The PAG is an important site in ascending
      pain transmission. It receives afferents from nociceptive neurons in the spinal
      cord and sends projections to thalamic nuclei that process nociception. The PAG
      is also a major component of a descending pain inhibitory system. Activation of
      this system inhibits nociceptive neurons in the dorsal horn of the sinal cord.
      The dorsal PAG is a major site for processing of fear and anxiety. It interacts
      with the amygdala and its lesion alters fear and anxiety produced by stimulation
      of amygdala. Stimulation of PAG produces vocalization and its lesion produces
      mutism. The firing of many cells within the PAG correlates with vocalization. The
      PAG is a major site for lordosis and this role of PAG is mediated by a pathway
      connecting the medial preoptic with the PAG. The cardiovascular controlling
      network within the PAG are organized in columns. The dorsal column is involved in
      pressor and the ventrolateral column mediates depressor responses. The major
      intrinsic circuit within the PAG is a tonically-active GABAergic network and
      inhibition of this network is an important mechanism for activation of outputs of
      the PAG. The various functions of the PAG are interrelated and there is a
      significant interaction between different functional components of the PAG. Using
      the current information about the anatomy, physiology, and pharmacology of the
      PAG, a model is proposed to account for the interactions between these different
      functional components.

PMID- 8545546
TI  - Arachidonic acid as a neurotoxic and neurotrophic substance.
AB  - In this article we summarize a wide variety of properties of arachidonic acid
      (AA) in the mammalian nervous system especially in the brain. AA serves as a
      biologically-active signaling molecule as well as an important component of
      membrane lipids. Esterified AA is liberated from the membrane by phospholipase
      activity which is stimulated by various signals such as neurotransmitter-mediated
      rise in intracellular Ca2+. AA exerts many biological actions which include
      modulation of the activities of protein kinases and ion channels, inhibition of
      neurotransmitter uptake, and enhancement of synaptic transmission. AA serves also
      as a precursor of a variety of eicosanoids, which are formed by oxidative
      metabolism of AA. AA cascade is activated under several pathological conditions
      in the brain such as ischemia and seizures, and may be involved in irreversible
      tissue damage. On the other hand, AA can show beneficial influences on brain
      tissues and cells in several situations. In a recent study using cultured brain
      neurons, we have found that AA shows quite distinct actions at a narrow
      concentration range, such as induction of cell death, promotion of cell survival
      and enhancement of neurite extension. The neurotoxic action is mediated by free
      radicals generated by AA metabolism, whereas the neurotrophic actions are exerted
      by AA itself. The observed in vitro actions of AA might be related to important
      roles of AA in brain pathogenesis and neural development.

PMID- 8545547
TI  - [Primal psychoanalytic manuscript. 100 years "Studies of Hysteria" by Josef
      Breuer and Sigmund Freud].
AB  - In 1895 Breuer and Freud jointly published the Studies on Hysteria, a work that
      Grubrich-Simitis regards as the very first psychoanalytic monograph. The author
      begins by outlining the intellectual context in which the work took shape and the
      initial reception accorded to it by contemporary medical science and sexology.
      The main focus of the discussion centres around those aspects of the book that
      mark it out as a genuinely psychoanalytic work - hitherto unknown quality of
      seeing and hearing, a radical change in the relationship between doctor and
      patient, the establishment of a new form of case presentation and the development
      of approaches adumbrating psychoanalytic theory and technique. In conclusion the
      author describes the scientific cooperation between Freud and Breuer, assigning
      to the latter his rightful place in the history of psychoanalysis, a status
      frequently denied him by Freudians.

PMID- 8545548
TI  - [The birth of metapsychology. On the current interpretation of "Entwurf einer
      Psychologie" (1895)].
AB  - The general attitude towards Entwurf einer Psychologie (1895) is to reckon it
      among Freud's pre-analytic writings, i.e. that part of his work later more or
      less disowned by the author. Schmidt-Hellerau challenges this assessment by Freud
      and many of his successors, demonstrating that the Entwurf can legitimately be
      regarded as a meta-theory resolving - or skirting- the old classification problem
      of whether psychoanalysis is a science or an art by connecting the hitherto
      dissociated spheres of soma and psyche and conceptualizing of physiological and
      psychological processes. See thus, the Entwurf reveals itself as a theoretical
      document of astonishing modernity and undiminished relevance in that it records
      Freud's ambitious attempt to overcome the mind-body schism and the divide between
      neurophysiology and psychology. And it is precisely this problem, the author
      contends, which Freud's later metapsychology--and the controversies it has
      aroused--revolves around.

PMID- 8545549
TI  - [The end of an illusion, Sigmund Freud and his 20th century].
AB  - At the end of the 20th century Eissler looks back to its beginnings and the
      outside figure of Sigmund Freud. What good have Freud's discoveries done? What
      progress have they promised and which of those promises have actually been
      redeemed? What kind of track record does psychoanalysis have to show for itself?
      The author undertakes a careful assessment of Freud's stature, his limitations
      and his scientific achievements, and comes to the skeptical conclusion that in
      the last resort it was in fact the founder of psychoanalysis who destroyed the
      illusion he himself had long subscribed to, i.e. that there is an indissoluble
      link between the increase of scientific knowledge and the salvation of homo
      sapiens. For Eissler's Freud the survival of humanity and the scientific
      civilization created by mankind are irreconcilable.

PMID- 8545550
TI  - [The prevalence of white coat hypertension in patients over 60 who came to a day
      hospital].
AB  - Over the last thirty years white coat hypertension has been the object of
      numerous studies which suggest that the interactions between doctor and patient
      and environmental, psychological circumstances suffice to determine a significant
      increase of arterial pressure in subjects who are generally normotense. The aim
      of this study was to evaluate the prevalence of white coat hypertension in
      elderly subjects with hypertension which had been diagnosed recently using the
      traditional sphygmomanometric method three times in the space of one week. We
      divided 69 patients (age range 60 to 82 years) into three groups depending on
      their clinic pressures, i.e. patients with isolated systolic, systo-diastolic or
      diastolic hypertension. Non invasive 24 h pressure ambulatory monitoring was
      performed in each subject using a Takeda recorder TM 2420 and adopting a protocol
      for single measurements at 15 minutes intervals between 08.00 and 20.00 (daytime
      measurements) and 30 minutes intervals between 20.00 and 08.00 (night-time
      measurements). Ambulatory monitoring with less than 60 recordings, and those
      where measurements were not taken for over 60 minutes during the day or 90
      minutes during the night were excluded from the study, and the mean daytime and
      24 h pressure load was calculated. Monitoring conducted in 60 subjects (39 males
      and 21 females) was considered valid. Statistical analysis of the mean arterial
      pressure values of each subject determined by the two methods was performed using
      a t-test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545551
TI  - Effects of human placental extract on hepatic drug metabolizing enzyme.
AB  - Effects of acute or subchronic administration of human placental extract (HPE), a
      worldwide clinically used agent, on hepatic drug metabolizing enzyme activities
      were evaluated in rats. Hepatic microsomal cytochrome P-450 (Cyt. P450) and
      cytochrome b5 (Cyt. b5) contents and cytosolic glutathione S-transferase (GST)
      activities were maximally induced after various periods of time following a
      single intraperitoneal injection of HPE (4 ml/kg) whereas microsomal UDP
      glucuronyltransferase (UDPGT) activities were inhibited significantly. All these
      altered effects were returned almost to the basal levels after 96 h of treatment.
      Subchronic treatment (30 days) with HPE (1,2 or 4 ml/kg) afforded a significant
      induction of Cyt. P-450 and Cyt. b5 levels and that of GST activities with a
      concurrent suppression of the activities of UDPGT and these results were found to
      be dose-dependent. However, microsomal NADPH cytochrome c reductase activity was
      not affected either by acute or subchronic treatment. The observed variations in
      the levels and activities of above house-keeping enzymes were discussed in
      relation to the possible carcinogenic risk of long-term treatment with this
      pharmaceutical agent.

PMID- 8545552
TI  - [Heat shock proteins in diabetes mellitus].
AB  - The Heat Shock Proteins (HSP) are a special category of proteins synthesized from
      2 types of cells, one originating from ordinary organs and the other highly
      specialized ones from mammals. Their synthesis originates from a reaction of the
      cells to heat shock and therefore it can be thought of as a defense mechanism
      activated by the cells to protect themselves from the damage done by heat. HSPs
      are also qualified as "molecular chaperons" since they are present at the
      assembling of other proteins and they protect them from any possible anomalous
      interactions even if they do not take an active part in the final making up of
      the protein itself. This chaperone role is the base of the hypothesis that HSPs
      could take part in the processing and presentation of the antigens. Two
      hypothesis have been formed on the role of HSPs in the immunological process. 1)
      HSP could be antigens that call for an immediate immunological reaction; 2) HSP
      could set off a self destructive mechanism brought on by an immunological
      reaction. From all this it emerges that the immunological reaction to HSP has two
      angles. One is protective in that it allows the cells to eliminate micro foreign
      organisms and the other is harmful due to a badly regulated immunological
      reaction. In some studies it has been demonstrated that patients with varying
      autoimmunological disorders as LES and rheumatoid arthritis (AR), have
      autoantibodies against HSPs. Moreover the HSPs of certain microorganisms induce
      the formation of autoantibodies in the host and the proliferation of T cells in
      the synovial fluid in patients with AR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545553
TI  - [Effectiveness of a test for verification of the presence of acari in house dust
      for the prevention of respiratory allergies in children].
AB  - Respiratory allergy and bronchial asthma in particular can be serious afflictions
      in younger as well as in older children. Therefore interest has been focused on
      methods for the prevention of atopy. The role and allergenic importance of
      Dermatophagoides pteronyssinus (Dpt) in house and other environments have been
      identified. This mite provokes asthma in children at an earlier age than pollens.
      However the most under-valued area of asthma prevention is environmental control.
      The steps may seem difficult at first, but the results will be well worth the
      efforts and the sacrifices. We report on the high effectiveness of the guanine
      detection test (Acarex) based on the colorimetric quantification of allergen
      sources in house dust (mattresses, pillows, upholstered furniture, carpets,
      moquettes, etc), which can be treated with house dust mite extermination products
      such as benzyl benzoate. The eradication measures will allow the parents to
      reduce the allergen exposure, to be monitored at 3-6 month intervals. The guanine
      detection test performed in our Division on house dust samples assembled by the
      patents of children with house dust mite induced asthma (study group) or pollen
      asthma (control group) yielded highly significant statistical differences.

PMID- 8545554
TI  - [Calcitonin gene-related peptide in diabetes mellitus type 2: a possible
      etiopathogenetic role].
AB  - The Calcitonin Gene-Related Peptide (CGRP) is a 37 aminoacid peptide displaying
      about 50% homology with amylin which is secreted from the pancreatic islets of
      Langerhans. The main form, the beta-CGRP, is produced by the enteric nervous
      system and perivascular nerves of the vasa vasorum. It represents the most
      powerful vasodilator yet discovered but its role is not yet completely clarified.
      Recently it has been implicated in the control of regional blood flow and some
      authors have hypothesized its role in the development of Non Insulin Dependent
      Diabetes Mellitus (NIDDM). CGRP and amylin seem to inhibit the release of insulin
      from beta-cells and to play a role in local paracrine control of insulin
      secretion. In addition it is also shown to decrease the uptake of glucose by
      striated muscle. This has led to the suggestion that CGRP might be a circulating
      hormone implicated in the regulation of peripheral insulin sensitivity. In this
      review we examine the possible role of CGRP in the development of peripheral
      insulin resistance and altered insulin secretion which is characteristic of
      NIDDM.

PMID- 8545555
TI  - [Autogenic training versus Erickson's analogical technique in treatment of
      fibromyalgia syndrome].
AB  - The AA have conducted a controlled trial to determine the efficacy of two verbal
      techniques for muscular relaxation on 53 patients with fibromyalgia. The subjects
      were assigned at random to a autogenous training group (27 patients) or a
      analogic Erickson's techniques group (26 patients). The autogenous training
      showed the presence of various limits: (1) application limits (in which notable
      difficulties had to be faced to train the patients with fibromyalgia to practice
      the Autogenous training due to the revelation of "intrusive thoughts" or
      "abreactions", or because of the incapacity of the patients to practice the
      exercises at home without hearing the instructions of a therapist); (2) limits of
      efficacy (the state of optimum training needed many therapeutic sittings in order
      to be achieved and the improvements regarded nighttime sleep and morning
      rigidity, however, these improvements were less than those obtained with the
      analogic Erickson's techniques). The Erickson's techniques have showed, instead,
      many advantages: numerous patients continued the treatment until it was finished;
      only a small number of therapeutic sittings were necessary. There was an
      improvement of all the parameters examined, superior compared to the results
      obtained in the group of patients treated with autogenous training.

PMID- 8545556
TI  - Irradiances and health risks associated with the use of UV lamps and sunbeds.
AB  - UV spectra of old sun lamps have been measured and found to contain significant
      amounts of UVC in addition to UVB and UVA irradiances. Their spectra are compared
      with that of a modern sunbed, a solar spectrum obtained with a solar elevation of
      29.3 degrees and the extraterrestrial UV spectrum. The effects of UVC on human
      skin is rarely studied, but we know that UVB can be harmful. Old UVR lamps for
      cosmetic tanning irradiate significant amounts of UVB and UVC, and are therefore
      not recommendable. However, several action spectra indicate small health risks
      with limited UVA exposure, but a drastic increase in the UVA doses may be one
      reason for the increasing skin malignancies observed in western countries.
      Further research to clarify these observations has to be carried out.

PMID- 8545557
TI  - [Pulmonary metabolism of beta-endorphin in asthmatic patients in asymptomatic
      periods and after bronchospasm induced by methacholine].
AB  - Blood concentration of endogenous beta-endorphines can change during the clinical
      evolution of chronic bronchopneumopathies. The authors assessed the beta
      endorphine concentrations in the pulmonary arterial and systemic arterial blood
      in 8 asthmatic patients during a symptom-free period and after methacholine
      induced bronchospasm. The beta-endorphine analysis was performed in duplicate dor
      each sample, by means of a RIA assay. There is not difference in the systemic
      arterial blood concentration of beta-endorphines between asthmatic patients and
      normal subjects. Furthermore, there is no change in the beta-endorphine blood
      concentration during the passage through the pulmonary tissue after methacoline
      induced bronchospasm.

PMID- 8545558
TI  - Cystic fibrosis: genetics and clinical applications.
AB  - The most recent advances about cystic fibrosis genetics are revised. Their
      clinical applications are reviewed: prenatal diagnosis, heterozygote screening,
      genotype and phenotype correlation, gene therapy.

PMID- 8545559
TI  - Follow-up of obese child.
AB  - A long-term follow-up which is still being carried out was started in the school
      year 1985-86 in a Primary School of Rome and we suggested a written diet of 1300
      calories and correct physical exercises. During this long follow-up we studied
      the changes in percentage of obesity of these subjects, considering their
      familiarity with obesity. It resulted that after a starting benefit due to the
      diet and the sport activity, which lasted till 1989, the youngsters with
      familiarity have subsequently regained the initial situation in 62.5% of cases,
      unlike those without familiarity who have kept themselves slim in 75% of cases.
      Even many other facts have been considered, as for example the psychologic
      approach, blood-tests for cholesterol, triglycerides etc, arterial pressure and
      above all a very careful feeding recall that has shown as the now obese subjects
      intake more calories than not obese one, with and excess of calories from fats to
      the detriment of carbon hydrates.

PMID- 8545560
TI  - Wernicke's encephalopathy post subtotal extended gastrectomy.
AB  - Wernicke's encephalopathy, neuropathy caused by a deficiency of thiamine is a
      syndrome characterized by memory troubles, mental confusion, ophthalmoplegia and
      nystagmus. The authors present a case that came up in a patient who underwent a
      subtotal gastrectomy because of malignant neoplasm of the stomach. More or less
      three months after the intervention the patient's general conditions were
      considerably declined and characterised by alimentary vomit, sensory obnubilation
      and neuromuscular deficit. After appropriate diagnostic ascertainments a
      repetition of the neoplastic disease was to be excluded locally and at a
      distance. So the authors analysed the different etiopathogenic possibilities to
      get a better clinical view of the syndrome in the surgical patient.

PMID- 8545561
TI  - A retrospective study on the incidence of lymphocytic gastritis in patients with
      Helicobacter pylori infection.
AB  - To investigate the relationship between lymphocytic gastritis and H. pylori
      infection, antral biopsy specimens from 162 patients with histological evidence
      of H. pylori infection, and from 177 subjects without colonization were
      retrospectively examined. Among patients with antral colonization, lymphocytic
      gastritis was identified in 8 cases (4.9%). Lymphocytic gastritis was not
      detected in specimens without H. pylori infection. Quantitation of the epithelial
      lymphocytic infiltration was carried out in all specimens and showed that cases
      with lymphocytic gastritis had a mean of 35.3 lymphocytes per 100 epithelial
      cells, compared with a mean of 2.6 and 2.4 respectively in chronic gastritis and
      normal mucosa. Among the 331 patients without lymphocytic gastritis, specimens
      colonized by H. pylori had a mean of epithelial lymphocyte counts significantly
      higher than those observed in both chronic gastritis and normal mucosa. These
      findings show a positive correlation between antral colonization by H. pylori and
      occurrence of lymphocytic gastritis, and suggest that the bacteria may have an
      important role in the induction of such particular form of antral inflammation.

PMID- 8545562
TI  - [The endothelium].
AB  - It is well known that the endothelial cells represent one of the most active and
      versatile elements in the human organism. In fact apart from being the lining of
      the vessel wall they exert both antithrombotic and prothrombotic functions.
      Endothelial cells regulate the vasomotor tone and also have a part in the
      different immunological and inflammatory process. All these functions are
      possible because the endothelial cells produce many receptors on their surface.
      This paper is a review of the latest data on different roles played and
      substances produced by endothelial cells.

PMID- 8545563
TI  - Stress reactivity in responder and non-responder hypertensives treated with
      verapamil and enalapril.
AB  - Hypertension was found to be associated with sympathetic overdrive but it is
      still debated if the antihypertensive agents can differently affect the stress
      response in hypertensive subjects. Through a psychophysiological study, we
      evaluated the effect of verapamil (V) and enalapril (E), both as monotherapy and
      association. Office BP was successfully reduced (< 145/90 mmHg) in 11 patients
      treated with V (V-Resp) and in 10 patients treated with E (E-Resp). Both the
      drugs were prescribed in 9 patients (V+E) who did not sufficiently lower their
      blood pressure (N-Resp) with monotherapy. Patients performed three stressors
      (color word stroop, cold pressor and handgrip). Extracardiovascular and
      hemodynamic functions were measured during baseline, stress and recovery periods.
      The response was evaluated adding the changes occurred in every phase of the
      psychophysiological session. This was performed before run-in and after any
      modification of the therapeutic intervention. The emotional arousal (phrontalis
      muscular contraction, skin conductance, peripheral temperature) was reduced when
      BP was normal. No change in BP reactivity was found. HR response decreased in V
      Resp and cardiac output increased in E-Resp while the vascular reaction was
      restrained in E-Resp and V-Resp. This was reduced also in N-Resp when they
      assumed V+E and normalized their arterial pressure. The findings indicate that
      the sympathetic reactivity may be modified by the therapy. In particular,
      verapamil restrained the cardiac stress response without lowering the cardiac
      output and was advantageously associated with enalapril to control the
      psychophysiological response in more resistant hypertensive patients.

PMID- 8545564
TI  - [Acyclovir in the treatment of varicella in immunocompetent children].
AB  - We evaluated safety and tolerance of acyclovir ACV per os in immunocompetent
      children affected by chicken-pox admitted to our department from January 1993 to
      December 1994. 183 subjects (102 males and 81 females) aged between 0 and 14
      years were treated by ACV (80 mg/kg/daily in 4 divided doses): 88 children were
      treated within 24 hours and 95 subjects within 48 hours from the onset of
      symptoms. The control group consisted of 83 children (52 males and 31 females)
      aged between 0 to 14 years. In all patients routine blood-test were performed and
      in those with respiratory illness Chest-Rx was also done. We evaluated clinical
      course, degree of eruption, the appearance and kind of complications, duration of
      hospitalization, the compliance and the potential consequences on specific
      antibody response. Our results show a faster improvement of clinical symptoms in
      treated patients with respect to the control group with shortening of the period
      of the fever, itch and appearance of new vescicles. The percentage of
      complications was lower in treated than in untreated patients. 16 cases tested
      for specific antibody response showed protective titers six months after
      treatment. In conclusion, ACV administered per os within 48 hours from onset of
      exanthema causes reduction of the period and the degree of general symptoms and
      exanthema, a lower incidence of complications even if non statistically
      significant. The drug is safe and well-tolerated.

PMID- 8545565
TI  - Circadian rhythms of fibrinogen and antithrombin III in liver cirrhosis.
AB  - BACKGROUND: Since acquired deficiencies of fibrinogen and antithrombin III are
      reported in liver cirrhosis and it is known that their plasma levels fluctuate
      during the day, the circadian rhythms of plasma fibrinogen and plasma
      antithrombin III were investigated in patients with compensated and decompensated
      cirrhosis, compared to healthy controls. METHODS: Three groups of subject were
      considered: (A) 10 healthy controls; (B) 10 patients with compensated liver
      cirrhosis; (C) 10 patients with decompensated liver cirrhosis. The fibrinogen and
      antithrombin III levels were determined in blood samples drawn in each studied
      subject during the span of a whole day and every three hours starting from
      midnight. The time-related data were analyzed by means of the "mean-group
      cosinor" method. RESULTS: Significant (p < 0.05) circadian rhythms were detected
      for the two variables in groups A and B, with peaks in the afternoon hours. No
      significant (p > 0.05) rhythms were found for group C. A significant (p < 0.05)
      difference was found between the three groups regarding the circadian rhythm of
      fibrinogen, and between controls and patients with compensated cirrhosis and
      between compensated and decompensated patients regarding the circadian rhythm of
      antithrombin III. CONCLUSIONS: These data suggest that in healthy subjects the
      plasma levels of fibrinogen and antithrombin III present daily variations with
      own circadian rhythms, and that liver cirrhosis is associated with
      chronobiological circadian changes in the coagulation system, related to the
      stage of the disease. This progressive derangement could be considered as an
      index of evolution in the natural history of cirrhosis of the liver.

PMID- 8545566
TI  - [Appearance of anti-DNA antibodies after treatment with interferon in a patient
      with chronic type C viral hepatitis].
AB  - The development of autoantibodies and autoimmune reactions has been reported
      during and after interferon (IFN) therapy. We report the case of a 55-years-old
      woman who developed anti-DNA and anti-nuclear antibodies after a 9 months
      treatment with alpha-IFN for chronic hepatitis C. Autoantibodies appearance has
      not modified the response to therapy; no clinical sign of autoimmune disease is
      appeared in a 5 months follow-up. HLA typing didn't show a genetic predisposition
      for the development of autoimmune reactions.

PMID- 8545567
TI  - [Immunopathogenic mechanisms in glomerulonephritis].
AB  - In this note the involvement of the immune system in glomerular injury is
      discussed: humoral and cell-mediated immune response, and soluble mediators of
      inflammation play an important role in the development of tissue injury. Clinical
      and experimental studies are in progress to better define the different
      pathogenic mechanisms involved in glomerular diseases and to give us new
      therapeutic approaches.

PMID- 8545568
TI  - Apnostresstherapy and psychosomatic pathology.
AB  - The authors, after having underlined history and peculiarities of the
      Apnostresstherapy, set out a range of 80 cases treated of infantile psychosomatic
      pathology. They describe diagnostic criteria with relative diagnosis of 80 cases,
      indications and modalities of the treatment. Clinical results, statistically
      evaluated, are reported, at first on the whole group and, then, in a differential
      way, in a group that have carried out the treatment for 3-6 months and in another
      group to whom the treatment length is been of 6-12 months.

PMID- 8545569
TI  - Chemical pleurodesis in the treatment of iterative neoplastic effusion.
AB  - The presence of a pleural effusion is a serious complication in the course of
      neoplastic diseases, where it assumes a determining medical and prognostic role.
      Thus the applications of adequate therapeutic methodologies becomes of primary
      importance to drain the effusion and to obtain an efficacious pleurodesis. In
      view of this the authors describe a case of iterative neoplastic pleural effusion
      which they have been able to observe recently.

PMID- 8545570
TI  - Accommodative amplitudes in the Early Treatment Diabetic Retinopathy Study.
AB  - PURPOSE: Accommodative amplitude in persons with diabetes was investigated using
      data collected as part of the Early Treatment Diabetic Retinopathy Study.
      METHODS: Accommodative amplitude was measured at the baseline visit in 1,058
      patients who had good visual acuity and who were less than 46 years old. Risk
      factors for low accommodative amplitude at baseline were evaluated using
      multivariable linear regression. Change in accommodative amplitude after
      photocoagulation was evaluated using paired t tests and repeated measures
      analysis of variance for the 578 patients who underwent follow-up measurements at
      the 4-month visit. RESULTS: Accommodative amplitudes in Early Treatment Diabetic
      Retinopathy Study patients were lower than normal accommodative amplitudes. Older
      age (P < 0.001) and increased duration of diabetes (P < 0.01) were risk factors
      associated with low amplitudes of accommodation in the Early Treatment Diabetic
      Retinopathy Study. Full scatter photocoagulation was associated with an
      apparently transient additional reduction in accommodative amplitude; a one third
      diopter loss in accommodative amplitude was demonstrated only at the 4-month
      visit (P < 0.001). CONCLUSION: This study demonstrates that diabetes and duration
      of diabetes, along with age, are important risk factors for reduced accommodative
      amplitude. These factors along with an apparently transient decrease in
      accommodative amplitude following scatter photocoagulation should be considered
      when assessing the accommodative needs of patients with diabetes and when
      discussing side effects of full scatter photocoagulation.

PMID- 8545571
TI  - A new classification of the retinoschises.
AB  - BACKGROUND: Two classifications of retinoschisis were published in the 1960s. A
      marked expansion of our knowledge of the diseases that give rise to retinoschisis
      indicates the need for an updated classification. METHODS: The new classification
      is based on the authors' clinical experience, an extensive review of the
      literature, and a survey of 20 vitreoretinal specialists. RESULTS: There are
      three types of retinoschisis: degenerative, hereditary, and secondary.
      Degenerative retinoschisis is very common and has been published extensively. In
      addition to the well known X-linked hereditary retinoschisis, there are less
      common pedigrees with autosomal recessive or autosomal dominant patterns. There
      are at least 18 ocular diseases that may show varying degrees of secondary
      retinoschisis. CONCLUSION: The many types of retinoschisis are divided into these
      major categories. The multiplicity of types is emphasized by the plural form of
      the term: "the retinoschises."

PMID- 8545572
TI  - Intraoperative observation of the vitreous base in patients with atopic
      dermatitis and retinal detachment.
AB  - PURPOSE: Patients with atopic dermatitis often develop tears around the vitreous
      base. An attempt was made to determine whether these patients had any
      abnormalities of the vitreous base that would lead to formation of such tears.
      METHODS: The medical records and intraoperative videotape recordings of 12
      patients with atopic dermatitis and retinal detachment who underwent vitrectomy
      were reviewed. RESULTS: Tears were located at the ora serrata or in the
      nonpigmented epithelium of the pars plana or plicata of the ciliary body. The
      vitreous gel at its base was condensed like fluffy cotton in all of the patients,
      whereas the retina and the continuing nonpigmented epithelium around the ora
      serrata were wrinkled by contraction of the overlying abnormal gel. CONCLUSION:
      Frequent occurrence of oral dialyses and tears of the nonpigmented epithelium of
      the ciliary body in patients with atopic dermatitis could be attributed to the
      abnormal vitreous gel at its base.

PMID- 8545573
TI  - Efficacy of fluid-air exchange during pars plana vitrectomy.
AB  - PURPOSE: Vitreous fluid that remains trapped in the peripheral vitreous cavity
      after vitrectomy with fluid-air exchange can result in a smaller than desired
      intravitreal gas bubble size. To evaluate the effectiveness of a single fluid-air
      exchange in dehydrating the vitreous cavity, we measured the rate and volume of
      posterior vitreous fluid migration after an initial fluid-air exchange. METHODS:
      Thirty-eight eyes undergoing vitrectomy for macular hole closure had measurements
      of posterior vitreous fluid accumulation at either 5, 10, 15, or 20 minutes after
      fluid-air exchange. RESULTS: An average of 0.38 ml of fluid accumulated
      posteriorly within 10 minutes after the initial fluid-air exchange compared to
      0.22 ml that accumulated after 5 minutes (P = 0.0003). A mean of 0.04 ml
      accumulated during each 5-minute interval between 10 and 20 minutes after the
      initial fluid-air exchange. CONCLUSION: Fluid composing 10% of the vitreous
      volume may migrate and accumulate posteriorly within 10 minutes of an apparently
      complete fluid-air exchange. Fluid aspiration after a 10-minute wait after the
      initial fluid-air exchange helps maximize vitreous cavity dehydration and should
      be employed when a large gas bubble is required after vitrectomy.

PMID- 8545574
TI  - Vitrectomy for accidental intraocular steroid injection.
AB  - BACKGROUND: Accidental perforation of the globe and intraocular injection of
      steroid is a potential complication of periocular injections. Final outcomes in
      eyes in which this complication has occurred have been reported to be
      unsatisfactory in the past. However, the advent of vitrectomy has altered their
      prognosis significantly. METHODS: A retrospective analysis was done of five cases
      of accidental intraocular steroid injection, treated by vitrectomy. Additional
      procedures involved treatment of retinal breaks (where required) with endolaser
      or transscleral cryopexy. Scleral buckling was done in one case. RESULTS: Barring
      one case in which retinal detachment developed, there were no postoperative
      complications. At last follow up all patients had satisfactory recovery of visual
      acuity; had attached retina; and quiet anterior chamber and vitreous cavities.
      CONCLUSION: Vitrectomy is associated with satisfactory results in cases of
      accidental intraocular steroid injection. Delay up to a few days does not seem to
      materially influence the outcome.

PMID- 8545575
TI  - An unusual case of cryptococcal endophthalmitis.
AB  - BACKGROUND: Cryptococcal endophthalmitis is a rare disorder, almost invariably
      diagnosed after enucleation or at postmortem examination. There are therefore few
      guidelines as to its identification or treatment. METHODS: A case of culture
      positive cryptococcal endophthalmitis in a patient with chronic uveitis was
      diagnosed by vitreous biopsy at the time of retinal detachment repair. The
      patient was treated with oral fluconazole for 5 months. All reported cases of
      cryptococcal endophthalmitis were reviewed and compared. RESULTS: After oral
      fluconazole therapy, the patient was culture negative on repeat tap. Despite
      conversion to culture-negative status, however, visual acuity declined to hand
      motions because of hyphema and hypotony. The organism was successfully identified
      as a non-neoformans species, Cryptococcus laurentii, previously unreported as an
      ocular pathogen. CONCLUSION: This unique case demonstrates that cryptococcal
      disease can be diagnosed antemortem by vitreous biopsy, and should be added to
      the differential diagnosis in cases of chronic smoldering uveitis. A non
      neoformans organism is also identified for the first time as a cause of ocular
      cryptococcosis. Fluconazole, used here for the only time of which we are aware to
      treat cryptococcal endophthalmitis, produced successful conversion to culture
      negativity and resolution of the uveitis.

PMID- 8545576
TI  - Clinical features and pathogenesis of Alport retinopathy.
AB  - BACKGROUND: Alport syndrome refers to the clinical triad of hereditary nephritis,
      sensorineural deafness, and ocular abnormalities. Ultrastructural findings in the
      lens capsule and in the renal glomeruli have provided evidence that abnormal
      basement membranes are elaborated in affected tissues of patients with this
      disorder. Recently, the results of several linkage studies have allowed the
      genetic defect in Alport syndrome to be mapped to a locus that codes for a
      subtype of type IV collagen (alpha 5) known to be present in glomerular basement
      membranes. In spite of these advances, the nature of the retinal flecks in Alport
      syndrome and the visual consequences of the flecks remain controversial. METHODS:
      Detailed psychophysical and electrophysiologic testing was performed in a young
      man with Alport syndrome. The concurrence of an unusually extensive fleck
      retinopathy and unilateral pseudophakia afforded a unique opportunity to assess
      the effect of the flecks on retinal function. RESULTS: No sensory deficits were
      present in the eye with clear media. CONCLUSION: Macular flecks in Alport
      syndrome are not associated with demonstrable retinal dysfunction. The authors
      address questions about the nature and pathogenesis of the flecks in light of new
      clinical and genetic information.

PMID- 8545577
TI  - Evaluation of ciliary body detachment in hypotony.
AB  - PURPOSE: This article describes an anatomic classification for the hypotonous eye
      and links this classification with approaches to the surgical treatment of this
      condition. The classification is based on very-high-resolution ultrasound scans
      and three-dimensional reconstruction of planar ultrasound scans. METHODS:
      Standard 10-MHz B-scans and very-high-resolution (40-60 MHz) scans were performed
      with a planar motor system using the immersion method. The anatomic changes in
      the hypotonous eye were classified and correlated with clinical and
      ultrasonographic findings at the time of therapeutic intervention and after
      resolution of the hypotonous condition. RESULTS: Hypotony is defined as low
      intraocular pressure most commonly due to ciliary body detachment or ciliary body
      dysfunction. With ciliary body detachment, three anatomically related causative
      types were identified: tractional hypotony, which has ultrasonographically
      demonstrable proliferative vitreociliopathy with membrane attachments between the
      ciliary body, iris, and formed vitreous; dehiscence hypotony, which has a
      modification in the scleral acoustic architecture consistent with a scleral break
      or wound dehiscence; and primary type hypotony, which has ciliary body detachment
      but no ultrasonographically demonstrable tractional component or scleral anatomic
      modification, but may have an iris scleral separation. CONCLUSIONS: Each type of
      ciliary body detachment hypotony may have a different management approach, so
      high-resolution ultrasound, particularly when shown with sequencing or three
      dimensional displays to demonstrate the extent of detachment, can aid in the
      selection and implementation of appropriate therapy.

PMID- 8545578
TI  - Effect of intravitreal tissue plasminogen activator on experimental subretinal
      hemorrhage.
AB  - PURPOSE: To study the effect of intravitreally injected tissue plasminogen
      activator (tPA) in an experimental model of subretinal hemorrhage. METHODS:
      Autologous blood was transsclerally injected into the subretinal space in 34
      albino rabbits. One day later tPA was injected into the posterior vitreous in 24
      eyes and saline was injected into 10 control eyes. Lysis of the subretinal blood
      was assessed ophthalmoscopically and retinal function was evaluated
      electroretinographically. RESULTS: In all eyes in which tPA was injected
      intravitreally 1 day after subretinal injection of blood, the formed subretinal
      clots was not visible within 24 hours of treatment. Liquefied subretinal blood
      that formed from clot lysis disappeared within 6 days. Conversely, in all saline
      injected control animals, the subretinal clots were unchanged at 24 hours and
      were observed for at least 3 days after injection. As a result of the presence of
      subretinal blood, scotopic electroretinogram amplitudes were markedly reduced in
      the tPA and saline-injected groups. In many eyes, blood migrated from the
      subretinal space into the vitreous, but it was detected later, was less severe,
      and cleared more rapidly after tPA injection. CONCLUSION: Intravitreal injection
      of tPA 1 day after subretinal injection of blood in rabbits facilitated more
      rapid lysis of the clotted blood, however, retinal damage was not prevented.

PMID- 8545580
TI  - Retinal oxygen distribution. Its role in the physiopathology of vasoproliferative
      microangiopathies.
AB  - PURPOSE: To study the role of oxygen distribution in the physiopathology of
      retinal vasoproliferative microangiopathies. METHODS: Experimental retinal branch
      vein occlusion was induced in miniature pigs, using argon laser photocoagulation.
      The microvascular modifications, the retinal histologic features, and the retinal
      oxygen distribution were studied within 48 hours of the occlusion, and 3 weeks
      later. The retinal oxygen distribution modifications were also studied in
      ischemic retinal areas treated by scatter argon laser photocoagulation. RESULTS:
      Impaired regulation and blood flow decrease in the vascular bed that was affected
      by a retinal branch vein occlusion and tissue hypoxia led to modifications of
      oxygen delivery resulted in a damage of the neuronal cells, whereas the abnormal
      permeability of the affected retinal vessel wall induced extracellular edema and
      disorganization of the inner retina. Three weeks after vein occlusion, retinal
      neovascularization occurred in ischemic/hypoxic retinas. The "critical PO2"
      (tissue oxygen partial pressure), which induces neovascularization in miniature
      pigs has not been determined. Photocoagulation of the ischemic retinal
      territories induced an increase of preretinal oxygen partial pressure, which is
      restored to the normal preretinal values. CONCLUSION: A retinal branch vein
      occlusion in miniature pigs represents a reproducible experimental model of
      retinal neovascularization. Oxygen partial pressure measurements of the ischemic
      retina confirmed the hypothesis that tissue hypoxia triggers neovascularization;
      laser photocoagulation should be applied over the whole ischemic retinal areas to
      eliminate hypoxia in the inner retina.

PMID- 8545579
TI  - Evaluation of retinal toxicity of acetylcholine in rabbit eyes.
AB  - PURPOSE: In vitreoretinal surgery, pupillary constriction may be required at the
      termination of a procedure especially if mechanical pupillary dilation was used
      in eyes filled with gas or silicone oil. A miotic agent instilled into the
      anterior chamber will sink and come into direct contact with retina in the
      aphakic or pseudophakic vitrectomized eye. Therefore, the retinal toxicity of
      acetylcholine, a miotic used for pupillary constriction, was studied. METHODS:
      Eight Dutch pigmented rabbit eyes were vitrectomized, had air-fluid exchange, and
      were injected with a 20% mixture of SF6. Subsequently eyes were randomly selected
      to have injections of 0.75 ml of 10 mg/ml acetylcholine (Miochol, Iolab Corp.,
      Claremont CA) versus 0.75 ml of lactated Ringer's solution. Short-term (2 weeks)
      and long-term (6 weeks) retinal toxicity was assessed by ophthalmoscopy,
      electroretinogram, and histology by light and electron microscopy at both times.
      RESULTS: Ophthalmoscopy, electroretinographic tracings, histology, and electron
      microscopy disclosed no significant abnormalities. CONCLUSIONS: Acetylcholine
      does not appear to have significant retinal toxicity even when undiluted
      solutions are in direct contact with the retina. We therefore postulate that
      intraoperative use of acetylcholine in previously vitrectomized eyes filled with
      gas or silicone is safe.

PMID- 8545581
TI  - Bilateral multiple arterial aneurysms.

PMID- 8545582
TI  - Acute multifocal posterior placoid pigment epitheliopathy: a theory of
      pathogenesis.

PMID- 8545583
TI  - Neovascular glaucoma in Takayasu's disease: a case report.

PMID- 8545584
TI  - Simultaneous syphilitic necrotizing retinitis and placoid chorioretinitis in
      acquired immune deficiency syndrome.

PMID- 8545585
TI  - Accidental parafoveal laser burn from a standard military ruby range finder.

PMID- 8545586
TI  - Intraocular pressure in hyperbaric oxygen therapy after intravitreal gas
      injection.

PMID- 8545587
TI  - Unilateral acute retinal necrosis syndrome with herpes simplex keratitis.

PMID- 8545588
TI  - Malignant fibrous histiocytoma: morphologic pattern or pathologic entity?
AB  - Since the concept of malignant fibrous histiocytoma (MFH) was introduced and
      subsequently popularized in the 1960's and 1970's, it has become widely regarded
      as the commonest soft-tissue sarcoma of adulthood. Although the initial notion
      that MFH was a true histiocytic tumor showing faculative fibroblastic
      differentiation has been disproved, and despite the lack of definable,
      reproducible diagnostic criteria and considerable immunophenotypic,
      ultrastructural and karyotypic heterogeneity, MFH is still accepted widely as a
      discrete clinicopathologic entity. On the other hand several recent studies have
      expressed considerable doubts about MFH, or at least pleomorphic MFH, as an
      "entity" and have suggested that it represents a common morphologic manifestation
      of a host of poorly differentiated sarcomas and, more rarely, other neoplasms.
      This article reviews the clinicopathologic features of MFH and its established
      variants in the context of this debate and considers the evidence for and against
      their continued acceptance as distinct entities or as a cohesive group. We
      conclude that the pleomorphic, giant cell and inflammatory variants each
      represent heterogeneous diagnostic groups which are hard to defend as cohesive
      entities, while the myxoid ("myxofibrosarcoma") and angiomatoid types are
      distinct, reproducible tumor types.

PMID- 8545589
TI  - Hemangiopericytoma: histopathological pattern or clinicopathologic entity?
AB  - The tumor designated by Stout and Murray as "hemangiopericytoma" (HPC) more than
      50 years ago continues to represent a source of uncertainty and disagreement
      among pathologists. In particular, questions exist regarding the synonymity of a
      hemangiopericytomatous growth pattern--defined by a monomorphic population of
      compact polygonal or bluntly fusiform cells and a branching stromal vascular
      pattern with a "staghorn" configuration--and the presence of a reproducible
      biological entity. It has been shown repeatedly that these same histologic
      features may be observed at least focally in a diversity of neoplasms, including
      "true" hemangiopericytomas, synovial sarcomas, mesenchymal chondrosarcomas,
      infantile fibrosarcomas, malignant fibrous histiocytomas, malignant peripheral
      nerve sheath tumors, leiomyosarcomas, endometrial stromal sarcomas, solitary
      fibrous tumors, myofibromas, malignant mesotheliomas, thymomas, sarcomatoid
      carcinomas, malignant melanomas, and "phosphaturic mesenchymal tumors." Despite
      their potential sharing of the microscopic attributes in question, such neoplasms
      have individualistic clinical features and can also be distinguished from one
      another by specialized pathologic analyses. HPC is "defined" in that context by
      reactivity for vimentin, with or without CD34 and CD57, but it lacks other
      immunodeterminants of epithelial, neural, and myogenous differentiation.
      Paradoxically, this phenotype is indeed associated with the presence of myogenous
      type cytoplasmic filaments in ultrastructural evaluations of HPC. Other lesions
      that may resemble "true" HPC--but which possess dissimilar subcellular and
      clinical characteristics--include solitary fibrous tumors, hemangiopericytomalike
      tumors of the sinonasal tract, and "infantile (congenital) hemangiopericytomas."
      Such observations suggest that the hemangiopericytoma is both a pathologic entity
      and a morphological pattern, and they emphasize the utility of adjuvant
      pathologic studies in this diagnostic context.

PMID- 8545590
TI  - Malignant rhabdoid tumors: a clinicopathologic review and conceptual discussion.
AB  - The malignant rhabdoid tumor (MRT) has been a controversial lesion since its
      seminal description. There is no consensus as to whether it represents a
      distinctive clinicopathological entity or, alternatively, a phenotypic pattern
      that is potentially common to several disparate neoplasms. MRT of the kidney is a
      childhood tumor that is associated with uniformly aggressive behavior, but it
      shows a wide spectrum of histologic, immunophenotypic, and cytogenetic findings.
      Malignant extrarenal rhabdoid tumors (MERTs) have been observed in pure form over
      a broader range of patient ages and anatomic locations, but they show substantial
      morphological and biological homology with renal MRT. Lastly, "composite"
      extrarenal rhabdoid tumors (CERTs)--in which recognizable "parent" neoplasms are
      admixed with MERTs--also have been recognized in several topographic sites. In
      aggregate, these observations suggest that "rhabdoid tumors" are a heterogeneous
      group of lesions with dissimilar lineages of differentiation. Particularly in
      CERTs, it is likely that the rhabdoid phenotype represents a common end point of
      clonal evolution in tumors of clearly different origins. Despite these caveats,
      the authors do support retention of the diagnosis of "rhabdoid tumor," because
      the affiliated morphological pattern is uniformly attended by aggressive
      biological behavior despite potential dissimilarities at a subcellular level.

PMID- 8545591
TI  - Poorly differentiated forms of papillary thyroid carcinoma: distinctive entities
      or morphological patterns?
AB  - The concept that poorly differentiated carcinomas (PDC) represent a group in an
      intermediate position in the spectrum of follicular cell-derived carcinomas of
      the thyroid gland is currently well established. Because at the well
      differentiated end of the spectrum there are two groups of entities with distinct
      biological characteristics, ie, the papillary carcinoma (PC) and the follicular
      carcinoma (FC), we examined the group represented by PCs to ascertain whether
      papillary carcinoma-related PDCs (pPDC) represent merely a histologic variant or
      a distinct pathologic entity. For this purpose 227 consecutive PCs were
      reclassified according to current criteria. The association between the presence
      of a tumoral pattern consistent with pPDC (response variable), and prognostic
      factors such as gender age, pTNM (predictive variables) was evaluated in terms of
      odds ratio statistics. One hundred eighty-three of 227 cases, defined as PCs met
      the World Health Organization criteria of the not otherwise specified (NOS) (79
      cases), microcarcinoma (65 cases), encapsulated (4 cases) and follicular (35
      cases) variants. Forty-four cases, defined as pPDCs, met those of the tall cell
      (39 cases), columnar cell PC (2 cases) and mixed tall cell-columnar cell PC (3
      cases) variants. Statistical analyses of the two groups of patients showed a
      significant correlation between differentiation and age above 40 years,
      extrathyroid tumor extension and low ratio of regional nodal involvement at the
      onset of disease. More strikingly they also showed that morphology, ie, a tumoral
      pattern consistent with pPDC (differentiation), is the strongest predictor of
      biological behavior including recurrences and recurrence-related deaths that
      appear to occur five and twenty times more frequently in pPDCs than in PCs,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545592
TI  - Nodular lymphocyte predominant Hodgkin's disease and anaplastic large-cell
      (CD30+) lymphoma: distinct entities or nonspecific patterns?
AB  - After many years of frustrating discussion concerning the nature of Hodgkin's and
      Reed-Sternberg cells and their role in the pathogenesis of Hodgkin's disease,
      interesting new information has recently been gathered through the use of new
      technologies. In light of these studies, Hodgkin's disease emerges as a
      heterogeneous disorder in which some separate new entities may be elucidated,
      such as nodular lymphocyte predominance Hodgkin's disease and anaplastic large
      cell CD30+ lymphoma. In this review, we focus on the morphologic, phenotypic,
      molecular, and clinical features that have served to partially clarify
      controversial issues.

PMID- 8545593
TI  - Angiosarcoma-like neoplasms of epithelial organs: true endothelial tumors or
      variants of carcinoma?
AB  - Past experience has shown the existence of tumors in various viscera that assume
      growth patterns that are usually associated with angiosarcomas of skin and soft
      tissue. The lineage of differentiation pursued by the former of these
      proliferations has been the subject of controversy, with some investigators
      concluding that "angiosarcomatoid" neoplasms of solid organs were, in actuality,
      variants of high-grade carcinomas. The latter statement does appear to have
      partial validity, inasmuch as immunohistologic, ultrastructural, and clinical
      data on "pseudovascular carcinomas" do support their basic identity with high
      grade epithelial malignancies of the breasts, skin, and lungs. Those lesions show
      uniform reactivity for keratin and epithelial membrane antigen, but they fail to
      express von Willebrand factor, CD31, or CD34, which are regarded as endothelial
      determinants. On the other hand, however, angiomatoid neoplasms of the thyroid
      gland are more complex; some represent indisputable carcinomas, others manifest
      seemingly "pure" mesenchymal phenotypes, and still others display a mixture of
      epithelial and endothelial phenotypes at ultrastructural and protein-chemical
      levels of specialized investigation. At present, it must be acknowledged that the
      distinction between angiomatoid thyroid carcinomas and "true" thyroid
      angiosarcomas is an academic one, because the prognoses and treatments for these
      lesions are essentially identical.

PMID- 8545594
TI  - Acute alveolar hypoxia increases endothelin-1 release but decreases release of
      calcitonin gene-related peptide in isolated perfused rat lungs.
AB  - The release and vascular effects of calcitonin gene-related peptide (CGRP) and
      endothelin-1 (ET-1) during acute alveolar hypoxia (O2 2%) were examined in
      isolated blood-perfused rat lungs. In 10 lungs, repeatedly ventilated with
      hypoxic gas for 5 min, samples from effluent blood were taken during hypoxia and
      analysed for plasma levels of CGRP-like immunoreactivity (-LI) and ET-1-LI. The
      plasma levels of ET-1-LI were significantly (p < 0.05) increased in hypoxic lungs
      (5.5 +/- 0.5 pmol l-1) compared with normoxic controls (3.7 +/- 0.56 pmol l-1).
      Plasma levels of CGRP-LI were significantly (p < 0.01) lower in hypoxic lungs
      (43.9 +/- 2.9 pmol l-1) than in normoxic controls (55.5 +/- 4.0 pmol l-1). No
      significant correlation was seen between perfusate peptide levels and pulmonary
      artery pressure (Ppa) during ventilation with normoxic or hypoxic gas. Infusion
      of the CGRP receptor blocker, CGRP, did not influence either the baseline Ppa or
      the development of the hypoxic pulmonary vasoconstriction response (HPV). In
      lungs undergoing HPV, 2 nmol l-1 ET-1 added to the perfusate, significantly
      reduced the hypoxic pressor response by 14 +/- 3% (p < 0.05), while addition of
      200 nmol l-1 ET-1 caused no significant changes in HPV. CGRP 2 nmol l-1 caused no
      significant attenuation of HPV (8.9%), while 200 nmol l-1 CGRP significantly
      reduced HPV by 16 +/- 5% (p < 0.05). To conclude: acute alveolar hypoxia changes
      release of CGRP and ET-1 to the perfusate in isolated rat lungs. The results
      further suggest that CGRP and ET-1 are not involved in the development and
      regulation of the hypoxic pulmonary vasoconstriction response.

PMID- 8545595
TI  - Expression of the proliferative cell nuclear antigen (PCNA) in adenocarcinoma of
      the gallbladder, and its relationship to prognosis.
AB  - Proliferative cell nuclear antigen (PCNA) has been correlated with degree of
      differentiation in some tumours, but information on PCNA expression in
      adenocarcinoma of the gallbladder is currently limited. Therefore, we examined
      PCNA expression in adenocarcinoma of the gallbladder, and its relationship to
      prognosis. The expression of PCNA was studied by immunohistochemistry in 70
      formalin-fixed, paraffin-embedded specimens of surgically removed adenocarcinomas
      of the gallbladder. The percentage of stained nuclei was recorded, and the PCNA
      labelling index (LI) was expressed as the ratio of labelled nuclei to the total
      number of nuclei counted. In all histological types, the PCNA-LI in the invasive
      zone of the tumour was higher than that in the luminal zone of the tumour (p <
      0.05). The PCNA-LI showed a stepwise increase with decreasing degrees of
      differentiation in both the invasive and the luminal zone of the tumour (p <
      0.01). In advanced adenocarcinomas, patients whose tumours had a PCNA-LI of less
      than 35 in the invasive zone had significantly longer survival rates than those
      with PCNA-LI equal to or greater than 35 (p < 0.01). Multivariate analysis, using
      the Cox proportional hazards model, indicated that a PCNA-LI > or = 35 in the
      invasive zone of the tumour was a significantly unfavourable prognostic factor (p
      = 0.002). The PCNA-LI of routinely processed specimens of adenocarcinoma of the
      gallbladder may be helpful for the evaluation of cell proliferation and
      prognosis.

PMID- 8545596
TI  - The 5-year reproducibility of calcium-related biochemical variables in
      postmenopausal women.
AB  - A total of 19 measured and derived bone-related biochemical variables were
      determined in 307 postmenopausal volunteers on two occasions, 5 years apart. The
      plasma variables with the highest coefficients of determination (r2) were plasma
      globulins, alkaline phosphatase, creatinine and calculated ionized and
      ultrafiltrable calcium. In the urine, the highest r2 values were in respect of
      fasting urine calcium excretion corrected for urine sodium, hydroxyproline
      excretion, and the maximal renal tubular reabsorption of calcium and phosphate
      (TmCa/GFR and TmP/GFR). The components of variance of TmCa/GFR and TmP/GFR show
      marked individuality but their methods determination meet the criterion for
      acceptable analytical goals. We conclude that most of the measured and derived
      bone-related biochemical variables in fasting plasma and urine are sufficiently
      reproducible in postmenopausal women to be useful for ranking individuals for a
      period up to 5 years.

PMID- 8545597
TI  - Effect of free fatty acids on the structure and properties of erythrocyte
      membrane.
AB  - The changes in the structure and properties of erythrocyte membranes that are
      induced by free fatty acids and their derivatives have been studied. The state of
      the membrane has been evaluated using the activity of membrane-bound
      acetylcholinesterase (AChE), the pyrene monomer/excimer fluorescence intensity
      ratio as an indicator of membrane lipid microviscosity and the fluorescence of
      membrane-bound 1-anilinonaphtalene-8-sulphonic acid (ANS). Free fatty acids and
      corresponding aliphatic aldehydes induced an inhibition of membrane-bound AChE,
      effectively decreased the bulk lipid and protein-bound lipid microviscosity, and
      quenched the fluorescence of membrane-bound ANS. The type and efficiency of the
      enzyme inhibition, as well as the efficiency of microviscosity decrease and ANS
      fluorescence quenching, depended on the hydrophobicity and the end group in the
      effector molecule. Therefore, it is proposed that fatty acids and related
      compounds perturb the lipid bilayer and disturb the protein-lipid complementarity
      of the human erythrocyte membrane.

PMID- 8545598
TI  - An image processing procedure for the assessment of normality curves of motility
      of human granulocytes in micropore filters.
AB  - With the conventional methods used in current practice, the results of human
      granulocyte motility assays are expressed by a numerical value that defines the
      leading front of cells into micropore filters. The authors have developed a fast
      procedure which allows the complete curve of polymorphonuclear leukocyte (PMN)
      migration to be obtained, from the initial plane of a filter to the maximum
      propagation depth. In this way, more information is given than that expressed by
      a single parameter. The paper describes the procedure used to determine the
      normality curves both for random and stimulated migration, according to a simple
      model which defines the PMN propagation in micropore filters. A normality band
      that defines variations due to the stochastic process is also reported.

PMID- 8545599
TI  - Potentiometric, enantioselective sensors for alkyl and aryl ammonium ions of
      pharmaceutical significance, based on lipophilic cyclodextrins.
AB  - Lipophilic alpha, beta and gamma cyclodextrins (CDs) have been systematically
      analysed in order to establish their selective binding to onium ions. They have
      been identified as excellent ionophores for a range of ions of vital importance
      in clinical, pharmaceutical and forensic analysis. From the results obtained we
      found the following. A peroctylated cyclodextrin provides a size-selective cavity
      for the binding and detection of onium ions. Potentiometric alpha, beta and gamma
      cyclodextrin-based electrodes selectively sense NH4+, NMe4+ and NEt4+ ions
      respectively. These experiments were performed in order to enable us to
      understand the nature of analyte recognition by the lipophilic cyclodextrins.
      Peroctylated alpha CD is a suitable ionophore for dopamine hydrochloride, -log[C]
      = 5.4, -log K = 2.0 (in serum level of Na+, K+, Ca2+) whereas peroctylated and
      2,6 didodecyl beta CD sense acetylcholine chloride, -log[C] = 5.0, -log K = 4.2
      (in serum level of Na+, K+, Ca2+) and creatinine hydrochloride, -log K = 2.7 (in
      serum level of Na+, K+, Ca2+), respectively. The 2,6 didodecyl beta CD responds
      to more bulky aryl ammonium ions such as the anaesthetics procaine, prilocaine
      and lignocaine hydrochlorides, -log K = 4.2 (in serum level of Na+, K+, Ca2+).
      Partially octylated alpha CD has been identified as an enantioselective sensor
      for ephedrine hydrochloride, -log K = 4.5 (in serum level of Na+, K+, Ca2+), -log
      Kpot+/- = 2.6, and related compounds such as amphetamine hydrochloride. The 2,6
      didodecyl beta CD is enantioselective for propranalol hydrochloride, -log K = 4.2
      (in serum level of Na+, K+, Ca2+), -log Kpot+/- = 2.7. Complexation has also been
      studied by electrospray mass spectrometry (ESMS).

PMID- 8545600
TI  - Interference of gadodiamide injection (OMNISCAN) on the colorimetric
      determination of serum calcium.
AB  - The interference of the non-ionic magnetic resonance contrast medium gadodiamide
      injection (OMNISCAN, Nycomed Imaging, Oslo, Norway) in the colorimetric
      determination of serum calcium has been investigated in commercial reconstituted
      serum, and in serum from rabbits and humans dosed with the contrast medium.
      Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and ion
      selective electrodes were used as reference methods for analysis of serum
      calcium. The results showed that the colorimetric reagent kit gave an apparent
      decrease in serum calcium after administration of a clinical dose of gadodiamide
      injection, and that the extent of interference is correlated to the concentration
      of the contrast medium. However, serum calcium was not changed when measured by
      means of an ion-selective electrode or ICP-AES. It is therefore recommended that
      colorimetric reagent kits should not be used for determination of serum calcium
      in samples taken within the first 24 h after administration of gadodiamide
      injection.

PMID- 8545601
TI  - Glucose content in human skin: relationship with blood glucose levels.
AB  - In order to ascertain the dynamic relationship between the extracellular glucose
      in upper skin layers and blood glucose, skin suction blisters were raised in six
      Type 1 diabetic patients during a three-step glucose clamp. Blister glucose
      closely paralleled venous glucose (mean of r = 0.998). However, in three patients
      blister glucose was constantly lower than plasma glucose and this appeared to be
      related to their slower formation of skin blisters. A substantial difference in
      skin blister suction time was noted among patients and it was found that suction
      time was linearly correlated to glycosylated haemoglobin (HbA1C) (n = 6, r =
      0.865, p = 0.026). It is concluded that a non-invasive blood glucose monitoring
      system could be successfully based on measurement of alterations in skin glucose
      contents.

PMID- 8545602
TI  - Serum beta-hexosaminidase isoenzymes are precursor forms.
AB  - The lysosomal enzyme beta-hexosaminidase (Hex, EC 3.2.1.52) was purified from
      human serum and placental tissue. On gel chromatography, Hex isoenzymes (Hex A, B
      and P) from serum showed a molecular weight of about 150 kDa, i.e. higher than
      the 120 kDa found for the placental (tissue) isoenzymes (Hex A and B). Sodium
      dodecyl sulphate polyacrylamide gel electrophoresis of non-reduced serum Hex A
      revealed two different subunits, denoted alpha and beta, corresponding to
      apparent molecular weights of 70 and 67 kDa, respectively. Serum Hex B and Hex P
      were composed of beta-subunits only. In contrast, the apparent molecular weights
      of the alpha- and beta-subunits originating from tissue were both 55 kDa.
      Reduction of tissue Hex A and Hex B resulted in cleavage of the beta-subunit into
      several fragments, whereas the beta-subunit in serum forms was resistant to this
      treatment. These results are consistent with the serum forms never having entered
      the lysosome prior to their release to the extracellular environment and serum
      forms can therefore be classified as precursor molecules. No mature (tissue)
      forms were found in serum. Isoelectric focusing before and after neuraminidase
      treatment of the serum isoenzymes showed that they all contained sialic acid and
      that Hex B and Hex P had an identical focusing pattern after desialylation. Serum
      beta-hexosaminidase is frequently elevated in liver disease, alcoholism and
      pregnancy and the results of the present study indicate that this is due to an
      increased synthesis and secretion of hypersialylated beta-subunits, rather than
      to release of intralysosomally stored enzyme.

PMID- 8545603
TI  - Trypsinogen is not activated during cardiac surgery with extracorporeal
      circulation.
AB  - Amylase, immunoreactive cationic trypsin(ogen) and complexes of cationic trypsin
      and alpha 1-proteinase inhibitor were analysed in plasma samples from 41 patients
      following cardiac surgery with extracorporeal circulation. Postoperative
      hyperamylasaemia was seen in seven patients (17%). In 10 patients there were
      elevated levels (> 100 micrograms 1(-1)) of immunoreactive cationic trypsin(ogen)
      on the first postoperative day. After gelfiltration, samples from these 10
      patients were analysed for trypsin-alpha 1-proteinase inhibitor complexes, with a
      solid-phase, double-antibody enzyme-linked immunoassay. The median preoperative
      level of trypsin-alpha 1-proteinase inhibitor complexes was 4.5 micrograms 1(-1)
      (range 3.3-11.9) and the median value on the first postoperative day was 5.5
      micrograms 1(-1) (range 2.6-14). The ratio between complexes and immunoreactive
      trypsin(ogen) decreased (p < 0.05) showing that activation of trypsinogen did not
      occur. This fact argues against the development of protease-mediated subclinical
      pancreatitis during cardiac surgery with extracorporeal circulation.

PMID- 8545604
TI  - Proatrial natriuretic polypeptide (31-67) in healthy individuals: day-to-day
      variation and influence of sex and age.
AB  - N-terminal parts of proatrial natriuretic polypeptide have been proposed to be
      sensitive and specific markers of congestive heart failure (CHF). A prerequisite
      for use of a clinical marker is knowledge of day-to-day variation and dependence
      on age and sex. Immunoreactive N-terminal proatrial natriuretic polypeptide (31
      67) (ir-N-ANP(31-67)) was measured in a clinically relevant population of healthy
      individuals. A total of 21 females (mean age 52 years, range 42-76) and 26 males
      (mean age 54 years, range 42-73), without cardiovascular disease, were included
      in the study. No correlation was found between ir-N-ANP(31-67) and sex. A
      statistically significant positive linear correlation (ir-N-ANP pmol 1(-1) = 182+
      (8.2 x age in years) (p = 0.004) was found between age and ir-N-ANP(31-67). For
      the youngest subjects (42 years) the expected mean ir-N-ANP(31-67) was 530 pmol
      1(-1), and for the oldest subjects (76 years) it was 800 pmol 1(-1). For all the
      subjects, the median ir-N-ANP(31-67) was found to be 626 pmol 1(-1) (range 300
      1151). The day-to-day variation was studied and no significant difference was
      found in the plasma concentration of two samples taken 2-5 days apart. Of the
      individual day-to-day variation, 95% would be expected to be in the interval from
      -244 to 188 pmol 1(-1) (mean +/- 2 x SD). We conclude that ir-N-ANP(31-67) rises
      with age. The age-dependent rise in ir-N-ANP(31-67) is modest, but should be
      taken into consideration in order to use ir-N-ANP(31-67) as a diagnostic marker
      of CHF. The day-to-day variation is found to be rather high and cannot be
      neglected if N-ANP(31-67) is to be used as a marker of asymptomatic heart
      failure.

PMID- 8545605
TI  - Cytosolic phospholipase A2 and cyclooxygenase-2 mediate release and metabolism of
      arachidonic acid in tumor necrosis factor-alpha-primed cultured intestinal
      epithelial cells (INT 407).
AB  - BACKGROUND: We have recently reported that tumor necrosis factor-alpha (TNF
      alpha), a pro-inflammatory cytokine that has been suggested to play a role in the
      pathogenesis of inflammatory bowel disease, potentiates phospholipase A2 (PLA2)
      stimulated arachidonic acid (AA) release and prostaglandin E2 (PGE2) formation in
      cultured intestinal epithelial cells (INT 407). The aim of the present study was
      to investigate which particular isoforms of PLA2 and cyclooxygenase (COX) are
      involved in these processes. METHODS: Cells were labeled with 14C-AA or 14C-oleic
      acid, and the amounts of released fatty acid and PGE2 were analyzed by thin-layer
      chromatography. mRNA was analyzed by reverse transcription and polymerase chain
      reaction. RESULTS: The cells contained mainly mRNA for cytosolic PLA2 (cPLA2) and
      only trace amounts of mRNA for group I and II PLA2. TNF-alpha potentiated the
      release of 14C-AA but not of 14C-oleic acid. The TNF-alpha-potentiated PGE2
      release was reduced after inhibition of cellular COX activity or mRNA synthesis.
      TNF-alpha increased the amounts of mRNA for COX-2 but not for COX-1. CONCLUSIONS:
      The results point to the possibility that TNF-alpha may modulate the intestinal
      mucosal content of biologically active AA metabolites by priming cPLA2- and COX-2
      mediated processes in the epithelial cells.

PMID- 8545606
TI  - Tumor cell-induced platelet aggregation in vitro by human pancreatic cancer cell
      lines.
AB  - BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is considered to be a
      critical step in hematogenous metastasis. METHODS: TCIPA was studied in vitro in
      six human pancreatic carcinoma cell lines (PC 3, PC 44, AsPC1, BxPC3, Capan2,
      Panc1). RESULTS: Whereas all cell lines induced aggregation of washed platelets
      in the presence of minimal amounts of platelet-poor plasma, five cell lines also
      induced aggregation of platelets in platelet-rich plasma. The thrombin-antagonist
      hirudin inhibited TCIPA in all cell lines indicating that TCIPA is thrombin
      dependent. Since pretreatment of tumor cells with phospholipase A2 or C inhibited
      TCIPA, the thrombin-generating activity might be confined to the tumor cell
      surface. Further support for a prothrombinase activity was provided by the
      observation that all cell lines were able to induce the aggregation of washed
      platelets after addition of purified coagulation factors II and V. CONCLUSIONS:
      Pancreatic carcinoma cells are able to induce platelet aggregation via activation
      of thrombin. This might support metastasis in pancreatic cancer and possibly
      explain the incidence of thrombosis in this tumor.

PMID- 8545607
TI  - The relationship between cholecystectomy, unoperated gallstone disease, and
      colorectal cancer. A necropsy study.
AB  - BACKGROUND: There may be an increased risk of colorectal cancer after
      cholecystectomy, but the literature is not consistent. It is also possible that
      any risk might be associated with gallstones rather than cholecystectomy.
      METHODS: In a prospective necropsy study of 8563 cases, all 219 cases of a
      previous cholecystectomy were pair-matched to subjects with gallstones and to
      subjects with a normal gallbladder. In a second study all 192 cases of colorectal
      cancer were pair-matched to cancer-free subjects. RESULTS: The odds ratio (OR)
      for developing colorectal cancer after cholecystectomy compared with a normal
      gallbladder was 1.0 (95% confidence interval, 0.30-3.34) and with unoperated
      gallstones was 0.88 (0.27-2.76). CONCLUSIONS: This study fails to support an
      association between cholecystectomy or gallstones and colorectal cancer. For
      those cases of colorectal cancer versus controls, the OR for previous
      cholecystectomy was 0.70 (0.23-2.04) and for gallstone disease was 0.93 (0.58
      1.48).

PMID- 8545608
TI  - Inflammation reduces mucosal secretion of hydrogen ions and impairs concentrating
      function and luminal acidification in feline gallbladder.
AB  - BACKGROUND: The gallbladder mucosa normally absorbs fluid and secretes H+ ions.
      The fluid secretion in inflamed gallbladders is induced by prostaglandins and
      mediated by intramural vasoactive intestinal peptide (VIP)-ergic nerves. METHODS:
      The influence of inflammation on gallblader contents due to secretion of H+ into
      the lumen. In animals with inflamed gallbladder this acid secretion was reduced;
      there was secretion of HCO3- and no evident acidification of the gallbladder
      contents. Injection of VIP antiserum or indomethacin restored H+ secretion and
      inhibited HCO3- and fluid secretion by the inflamed gallbladder mucosa. An
      impaired acidification of the gallbladder contents due to mucosal inflammation
      may reduce the solubility of calcium salts in gallbladder bile and increase the
      risk of their precipitation in the lumen. CONCLUSION: Mucosal inflammation
      reduces H+ secretion and impairs acidification of the gallbladder contents.

PMID- 8545610
TI  - Hepatic lymph nodes as follow-up factor in primary biliary cirrhosis. An
      ultrasound study.
AB  - BACKGROUND: The aim of this study was to investigate whether changes in lymph
      node size in the hepatoduodenal ligament reflect changes in biochemical and
      histologic markers of cholestasis, hepatocellular damage, and humoral
      immunoreactivity in patients with primary biliary cirrhosis (PBC). METHODS:
      Twenty-three consecutive patients were examined with repeated liver biopsies,
      laboratory tests, and ultrasonographic examinations of the hepatoduodenal
      ligament. The effect of treatment with ursodeoxycholic acid (UDCA) on these
      factors was also studied. RESULTS: A correlation was found between changes in
      lymph node size and changes in markers of hepatocellular damage, cholestasis, and
      humoral immunoreactivity and also with intralobular inflammation. In the UDCA
      treated patients the node size decreased slightly during 2 years of treatment,
      whereas it was unchanged in the control group (p = 0.0528). CONCLUSIONS: Changes
      in the size of the lymph nodes in the hepatoduodenal ligament may reflect
      inflammation and cholestasis in PBC and thus be a valuable indicator in the
      follow-up of patients with this disease.

PMID- 8545609
TI  - Leukocyte adhesion molecules in the liver and plasma cytokine levels in endotoxin
      induced rat liver injury.
AB  - BACKGROUND: The interactions between polymorphonuclear neutrophils (PMNs) and
      sinusoidal endothelial cells (SECs) have been known to be involved in the
      pathogenesis of acute liver injury. It has been also reported that tumor necrosis
      factor-alpha (TNF-alpha) up-regulates ICAM-1 expression on SECs and that
      interleukin-8 (IL-8) provokes rapid activation of CD11/CD18 on PMNs. These
      findings expand into the relationship between the expression of leukocyte
      adhesion molecules (ICAM-1, CD11a/CD18 and CD11b/CD18) in liver tissues and
      plasma TNF and IL-8 levels after lipopolysaccharide (LPS)-induced liver injury in
      rats. METHODS: Male Wistar rats weighing 200-250 g were treated with 2 mg LPS/kg
      intravenously in a 0.2- to 0.25-ml volume. Liver and blood samples were obtained
      at 1, 3, 8, and 12 h after LPS exposure. Plasma TNF and IL-8 levels were measured
      using bioassay and specific enzyme-linked immunosorbent assay, respectively.
      Liver samples were fixed and studied by immunohistochemistry using specific
      monoclonal antibodies against ICAM-1, CD11a, and CD11b. RESULTS: The TNF level
      showed a peak at 1 h (23.3 +/- 11.4 IU/ml), and the IL-8 level showed a peak at 3
      h (343.1 +/- 110.5 ng/ml) after LPS exposure. An increase in the number of PMNs
      in the liver was observed as early as 1 h and continued until 12 h after LPS
      exposure. PMNs adhered to degenerated SECs and hepatocytes. ICAM-1 on SECs was
      diffusely and strongly expressed at 8 h, and PMNs adhered to SECs expressed both
      CD11a and CD11b. ICAM-1 was also observed on hepatocytes. CONCLUSION: These data
      suggest that PMN-SEC and PMN-hepatocyte interactions via leukocyte adhesion
      molecules, related to inflammatory cytokines such as TNF and IL-8, exist and play
      an important role in the pathogenesis of acute liver injury.

PMID- 8545611
TI  - Gastric mucosal protection against penetration of carcinogens into the mucosa.

PMID- 8545612
TI  - The origin of nocturnal intragastric pH rises in healthy subjects.
AB  - BACKGROUND: Duodenogastric reflux (DGR) can produce transient increases in
      gastric luminal pH. It has been proposed that intragastric pH-metry is a reliable
      method for the detection of DGR. Our aim was to test the hypothesis that
      nocturnal increases in antral pH are due solely to DGR. METHODS: Gastric pH was
      monitored overnight using two glass pH electrodes, one in the antrum adjacent to
      the tip of a nasogastric tube and one in the corpus. Scheduled antral aspirations
      were performed hourly to determine base-line concentrations of total bile acids
      (TBA; a marker of DGR) and thiocyanate (SCN; a marker of swallowed saliva).
      Additional, triggered aspirations were performed if antral pH exceeded 3.0 for 1
      min or more (PHAP; period of high antral pH). TBA and SCN were considered to be
      increased if they exceeded the 90th percentile of values determined in scheduled
      aspirates (TBA, 0.88 mM; SCN, 0.67 mM). RESULTS: In 28 of the 62 samples whose
      aspiration was triggered by a PHAP the pH was less than 3.0, and the sample was
      not considered to be representative. In the remaining 34 samples the antral
      luminal pH and the sample pH were concordant; TBA alone was increased in 6
      samples, SCN alone was increased in 6 samples, and TBA and SCN were both
      increased in another 3 samples. Thus, DGR and swallowed saliva alone or in
      combination accounted for only 15 (45%) of the PHAP in which adequate gastric
      samples were obtained. CONCLUSION: Samples of gastric antral contents often do
      not reflect accurately the acidity of gastric fluid in contact with a luminal
      antral pH electrode. Nocturnal increases in antral pH, detected by a luminal
      electrode, are frequently due to mechanisms other than duodenogastric reflux or
      swallowed saliva. Thus, antral pH-metry is not suitable for monitoring the
      occurrence of duodenogastric reflux.

PMID- 8545613
TI  - Effects of ranitidine on gastric vesicles containing H+,K(+)-adenosine
      triphosphatase in rats.
AB  - BACKGROUND: To ascertain the mechanism for rebound acid hypersecretion after
      treatment with an H2-receptor blocker, we investigated the effects of ranitidine
      on gastric H+,K(+)-adenosine triphosphatase (ATPase) in rats. METHODS: Male
      Wistar rats received ranitidine (1-50 mg/kg body weight intraperitoneally twice a
      day for 5 days). The rats were starved for 15 h after the last treatment and then
      killed, and gastric vesicles containing H+,K(+)-ATPase were prepared. RESULTS:
      Treatment with ranitidine dose-dependently increased protein content in the
      gastric vesicular fraction purified from the gastric mucosa without changing
      total protein content. Ranitidine also increased the content of a 94,000-dalton
      protein, the catalytic subunit of H+,K(+)-ATPase. On the other hand, ranitidine
      did not affect the specific activity of the enzyme (mumol/min/mg of the gastric
      vesicular protein). Since gastric vesicles in the fasting state mainly consist of
      the tubulovesicular membrane, these results suggest that ranidine administration
      increases total tubulovesicular H+,K(+)-ATPase content (mumol/min/rat) by
      increasing the number of tubulovesicles per parietal cell. The ranitidine-induced
      increase in total tubulovesicular H+,K(+)-ATPase activity was still evident 1
      week after treatment and returned to control level 1 month later. CONCLUSIONS:
      All these findings suggest that the increased content and total activity of
      tubulovesicular H+,K(+)-ATPase after ranitidine treatment may contribute to the
      mechanism for acid rebound after H2-blocker therapy.

PMID- 8545614
TI  - Structure of calvaria after gastrectomy. An experimental study in the rat.
AB  - BACKGROUND: Gastrectomy induces bone loss, suggesting that the stomach is
      important for calcium homeostasis. In this study we examined the effects of
      gastrectomy, with or without CaCl2 supplementation, on the structure of the
      calvaria of the rat. METHODS: The calvaria were dissected out and
      transilluminated, and the calvaria thickness was measured before (micrometer) and
      after fixation and sectioning (microscopy). Sections of the skull were analysed
      planimetrically for bone tissue area, using computer-assisted image analysis.
      RESULTS: The time course of the gastrectomy-produced bone loss was studied. After
      4 weeks the remaining bone represented about 70% of that in control rats, and
      after 8 weeks the value was 50%. The thickness of the calvaria was lower in
      gastrectomized rats than in sham-operated controls. Bone marrow and samples from
      liver and spleen were examined; no differences were found between experimental
      and control groups. Daily ingestion of 100 mg CaCl2.2H2O did not prevent the bone
      loss. CONCLUSIONS: It is unlikely that the gastrectomy-produced bone loss
      reflects calcium deficiency. The results rather support the view that the stomach
      is important for calcium homeostasis through another mechanism, perhaps involving
      a hypothetical gastric hormone.

PMID- 8545615
TI  - Lack of association of Helicobacter pylori seroprevalence and gastric cancer in a
      population with low gastric cancer incidence.
AB  - BACKGROUND: Previous studies have suggested that infection with Helicobacter
      pylori is associated with an increased risk of gastric adenocarcinoma. METHODS:
      We examined the sera of 111 Caucasian patients with histologically confirmed
      gastric cancer (36 with cancer of the cardia, 70 with cancer of the body or
      antrum, and 5 with stump carcinomas after Billroth-II procedures) and 111 age
      matched controls with colorectal carcinomas for the presence of H. pylori IgG
      antibodies by enzyme-linked immunoassay. RESULTS: The overall prevalence of H.
      pylori infection was 58.6% (65 of 111) in gastric cancer patients as compared
      with 50.5% (56 of 111) in matched control subjects (odds ratio, 1.39; 95%
      confidence interval, 0.82 to 2.36). Carcinomas of the cardia were not linked to
      H. pylori infection (odds ratio, 1.25; 95% confidence interval, 0.65 to 2.46),
      nor diffuse or intestinal-type carcinomas (odds ratios, 1.79 and 1.0; 95%
      confidence intervals, 0.69 to 4.67 and 0.34 to 2.91, respectively). Age, sex, and
      height of the IgG immune response did not affect risk. CONCLUSIONS: In contrast
      to previous results, these data do not provide evidence that the contribution of
      H. pylori infection to the carcinogenesis of gastric cancer is of major
      significance in a population with low gastric cancer rates and with high
      socioeconomic status.

PMID- 8545616
TI  - A 12-year follow-up study of chronic gastritis and Helicobacter pylori in a
      population-based random sample.
AB  - BACKGROUND: The study is a 12-year endoscopic follow-up investigation on the
      course of chronic gastritis and Helicobacter pylori infection in a sample of 81
      Estonian people. METHODS: The series is a subset from a random sample of 227
      subjects in whom a gastroduodenal endoscopy had been done. The grade of
      superficial gastritis (SG), atrophy, and colonization of the mucosa by H. pylori
      was evaluated in biopsy specimens from both antrum and corpus in accordance with
      the principles of the Sydney System. RESULTS: The healing rate of the H. pylori
      and gastritis was 0.3% (3 of 81); H. pylori colonization with gastritis developed
      in 5 of 81 during the follow-up. The mean prevalence of atrophic gastritis (AG)
      was three times more common in the corpus than in the antrum on the average. The
      formation of new cases of AG and the disappearance of AG were quite equal during
      the follow-up, and the overall changes in the grade of SG and atrophy were slow.
      The mean life span of corpus AG was nearly three times as long as that of antrum
      AG. In the antrum the grade of chronic inflammation correlated positively with
      the grade of H. pylori colonization. In cases of SG a low grade of colonization
      of H. pylori in the antral mucosa in connection with moderate inflammation
      predicted a reduction or even a healing of gastritis in the long term.
      CONCLUSIONS: New H. pylori infections with subsequent gastritis may occur in
      adulthood; a healing of gastritis occurs but is a quite rare event in the course
      of the 12-year follow-up. Further, in the present random sample of Estonian
      people atrophic corpus gastritis did not show an overall progression, in contrast
      to our earlier findings.

PMID- 8545617
TI  - Eradication of Helicobacter pylori infection in patients with non-ulcer
      dyspepsia. Effects on basal and bombesin-stimulated serum gastrin and gastric
      acid secretion.
AB  - BACKGROUND: This study evaluates the effect of eradicating Helicobacter pylori on
      basal and bombesin-stimulated gastric acid secretion and serum gastrin in non
      ulcer dyspepsia. METHODS: Before and 1 month after an attempt to eradicate H.
      pylori basal and bombesin-stimulated gastric acid outputs were measured in 23
      patients. H. pylori was eradicated in 15 patients (group A) but not in the other
      8 (group B). Incremental gastric acid output was calculated by subtracting basal
      from bombesin-stimulated values. RESULTS: Basal acid output increased
      significantly (p = 0.01) after therapy in group A (delta 1.6 +/- 0.6 mmol/h) but
      not in group B (delta 0.2 +/- 0.5 mmol/h). Incremental gastric acid output
      decreased distinctly (delta-3.9 +/- 1.4 mmol/h) after therapy in group A (p =
      0.02) but not in group B (delta-2.2 +/- 1.7 mmol/h). Basal serum gastrin
      decreased significantly (p < 0.005) after therapy in group A (delta-9 +/- 4 pM)
      but not in group B (delta-1 +/- 2 pM). Integrated serum gastrin responses to
      bombesin decreased markedly (p < 0.001) after therapy in group A (delta-5.0 +/-
      1.6 nM*60 min) but slightly in group B (delta-0.9 +/- 1.3 nM*60 min) (p < 0.05).
      CONCLUSIONS: In patients with non-ulcer dyspepsia basal serum gastrin
      concentrations decrease but basal gastric acid outputs increase after eradication
      of H. pylori. Bombesin-induced increments in gastric acid output, however,
      decrease in parallel with gastrin release.

PMID- 8545618
TI  - Effects of plain and controlled-ileal-release budesonide formulations in
      experimental ileitis.
AB  - BACKGROUND: Budesonide combines a topical anti-inflammatory activity with high
      first-pass hepatic extraction. This study compared the effects of plain and
      controlled-ileal-release (CIR) formulations of budesonide on intestinal
      inflammation. METHODS: Ileitis was induced in hamsters by an intraluminal
      injection of trinitrobenzene sulphonic acid. Inflammation was assessed
      histologically and by measuring mastocytosis and myloperoxidase activity. Adrenal
      pituitary axis suppression was assessed by radio-immunoassay of plasma cortisol.
      Animals received budesonide (200 or 800 micrograms/kg/day), CIR budesonide (200
      micrograms/kg/day), or placebo. RESULTS: Plain budesonide (200 micrograms/kg/day)
      did not reduce intestinal inflammation despite significantly lowered plasma
      cortisol levels. Plain budesonide (800 micrograms/kg/day), on the other hand,
      significantly reduced intestinal inflammation but further decreased plasma
      cortisol levels. CIR budesonide (200 micrograms/kg/day) was as effective in
      reducing inflammation as plain budesonide (800 micrograms/kg/day). CONCLUSIONS:
      CIR budesonide was significantly more effective in reducing intestinal
      inflammation than plain budesonide. These results suggest that the site of
      delivery influences the effectiveness of budesonide and that local (topical)
      rather than systemic action of this compound is primarily responsible for its
      anti-inflammatory effect.

PMID- 8545619
TI  - Stimulation of butyrate absorption in the human rectum in vivo.
AB  - BACKGROUND: Models of short-chain fatty acid absorption have focused on the
      stimulation of sodium absorption, an effect mainly located in the proximal colon
      of man. With the present efforts to utilize butyrate enemas as a treatment of
      ulcerative colitis, it seemed important to assess the transport in the rectum.
      METHODS: Non-equilibrium dialysis of the rectum was applied by placing dialysis
      bags containing various electrolyte solutions in the rectum of volunteers for 30
      min. In this period changes in ion concentrations were linear with time. Net
      absorption and secretion rates were calculated from the change in fluid
      composition. RESULTS: Sodium absorption was highest (24 +/- 8 mumol/cm2 h) in the
      presence of chloride and lowest (16 +/- 2 mumol/cm2 h) in the presence of
      bicarbonate and butyrate. Butyrate (70 mmol/l) was absorbed at a high rate of 7.1
      +/- 2.2 mumol/cm2 h, independent on the presence of chloride, and was accompanied
      by increased bicarbonate secretion. Butyrate absorption increased to 9.6 +/- 1.8
      mumol/cm2 h in sodium-free high-potassium media containing bicarbonate.
      CONCLUSION: The results show that it is possible to increase butyrate uptake by
      manipulation of the electrolyte composition in the rectal lumen. Maximal uptake
      occurred with an electrolyte composition that was similar to the natural rectal
      content. The information gathered could be useful in designing enemas for trial
      in ulcerative colitis, provided the findings can be confirmed in these patients.

PMID- 8545620
TI  - Centralized registration, prophylactic examination, and treatment results in
      improved prognosis in familial adenomatous polyposis. Results from the Danish
      Polyposis Register.
AB  - BACKGROUND: Over the last few decades numerous regional and national registers
      have been established all over the world with the aim of improving survival in
      familial adenomatous polyposis (FAP). The Danish Polyposis Register was founded
      in 1971 and coordinates the screening and subsequent prophylactic colectomy of
      FAP patients. METHODS: The crude cumulative survival in 321 patients (205
      probands and 116 call-up cases) with verified FAP was calculated in accordance
      with the life-table method. RESULTS: At the time of diagnosis of FAP only 2 of
      116 (2%) had colorectal cancer versus 142 of 205 probands (69%). The 10-year
      cumulative survival was 94% (95% confidence limits, 89-99) in call-up cases
      compared with only 41% (34-49) in probands (p < 0.00001), and survival improved
      significantly (p < 0.00001) after the establishment of the Danish Polyposis
      Register. CONCLUSION: The establishment of a centralized polyposis register has
      resulted in a substantial improvement of the prognosis in FAP.

PMID- 8545621
TI  - Central 5-hydroxytryptaminergic function in irritable bowel syndrome.
AB  - BACKGROUND: Psychological factors may contribute to the aetiology and
      exacerbation of symptoms in irritable bowel syndrome (IBS), suggesting that the
      central nervous system may be an important site of dysfunction in IBS. Hormonal
      responses after a serotonergic challenge assess the functional integrity of
      central 5-hydroxytryptaminergic pathways and are diminished in depression. The
      aim of this study was to determine whether hormonal responses in IBS after a
      serotonergic challenge would be decreased, as in depression, or exaggerated, as
      have been reported in another functional gastrointestinal disorder, nonulcer
      dyspepsia. METHODS: Fourteen IBS patients, 16 healthy volunteers, and 9 patients
      with inflammatory bowel disease were given 30 mg d-fenfluramine, a selective
      stimulus to central 5-hydroxytryptaminergic pathways. RESULTS: Plasma prolactin
      and cortisol concentrations during the following 5 h increased to a similar
      extent in all three subject groups, despite increased levels of anxiety and
      depression (as scored on the Hospital Anxiety and Depression Scale and Beck
      Depression Inventory) in the IBS and inflammatory bowel disease patients compared
      with the healthy controls. Base-line cortisol concentration correlated with the
      magnitude of affective disorder. CONCLUSION: In contrast to the alterations of
      central 5-hydroxytryptamine receptor sensitivity seen in depression and non-ulcer
      dyspepsia, central 5-hydroxytryptaminergic pathways function normally in IBS.

PMID- 8545623
TI  - The Gordian Knot. Proceedings of a symposium. Oslo, Norway, January 21-22, 1994.

PMID- 8545624
TI  - The clinical significance of hiatus hernia.
AB  - A close association has been found between hiatus hernia (HH) and reflux
      symptoms, oesophagitis, and other abnormalities known to be related to gastro
      oesophageal reflux disease (GORD). However, GORD is not always associated with HH
      and HH is not always associated with GORD. If a patient suffers from symptoms
      compatible with GORD, the finding of a HH may be taken to support the diagnosis.
      In a patient with an established diagnosis of GORD the finding of a HH may
      emphasize the severity of the disease, particularly so if the HH is large.

PMID- 8545622
TI  - The predictive value of symptoms in gastro-oesophageal reflux disease.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) must be distinguished from
      functional dyspepsia and peptic ulcer disease because, albeit similar
      symptomatology, they are different diseases with greatly differing pathogenesis
      and treatment. METHODS: A new endoscopic grading of reflux oesophagitis was
      applied in two large prospective studies. RESULTS: High consistency of endoscopic
      findings and low predictive value of symptoms. CONCLUSIONS: The low predictive
      value of symptoms stresses the importance of applying solid endoscopic criteria
      in the assessment of GORD.

PMID- 8545625
TI  - Quality of life in upper gastrointestinal disorders.
AB  - BACKGROUND: There is increased interest in the concept 'quality of life'.
      Available instruments are defined and discussed, with special emphasis on
      reliability and validity. Research on quality of life in patients with upper
      gastrointestinal disorders is reviewed, and our own results presented. METHODS:
      The Psychosocial Adjustment to Illness Scale was used to compare 100 patients
      with functional dyspepsia and 100 patients with duodenal ulcer in a cross
      sectional study, and to monitor the quality of life of 74 duodenal ulcer patients
      in a longitudinal phase. RESULTS: The quality of life of patients with functional
      dyspepsia was more negatively affected than that of patients with duodenal ulcer.
      After half of the patients had received short-term cognitive psychotherapy and
      all had received prophylactic H2-blocker treatment after ulcer relapse, quality
      of life improved in both the treatment group and the control group. Seventy-four
      patients with recurrent duodenal ulcers reported higher satisfaction with the
      health care system, improved sexual relationship, and less psychological distress
      one year after cure of the ulcer disease by the eradication of Helicobacter
      pylori compared to before. CONCLUSIONS: Reliable and valid instruments are
      available to measure quality of life, and will probably gain increased importance
      in future medical research. In patients with recurrent duodenal ulcer disease,
      quality of life improves with the eradication of Helicobacter pylori.

PMID- 8545626
TI  - Gastro-oesophageal reflux and chronic respiratory disease in infants and
      children: surgical treatment.
AB  - BACKGROUND: Many infants have chronic respiratory symptoms related to gastro
      oesophageal reflux. The reflux seems to be due to a motility disorder, possibly
      because of an immature neuro-hormonal system. Most infants outgrow the disorder.
      Infants and children with severe symptoms and poor response to medical treatment
      may benefit from operation. Nissen fundoplication is the most commonly used
      procedure. In some children it is necessary to add a pyloroplasty to the
      fundoplication because of slow gastric emptying. METHODS: From May 1991 to March
      1993 eight children with severe gastro-oesophageal reflux disease were operated
      on using the Nissen fundoplication procedure. RESULTS: Seven to 29 months after
      the operation all children are much better. CONCLUSIONS: Children who do not
      respond to 6 weeks with aggressive medical treatment should be referred to
      surgery.

PMID- 8545627
TI  - Is this a reflux patient or is it a patient with functional dyspepsia with
      additional reflux symptoms?
AB  - Patients with pyrosis or regurgitation as the dominating symptoms have gastro
      oesophageal reflux disease (GORD). However, patients with more atypical symptoms
      may also suffer from it. The disease is usually chronic and patients who have
      additional oesophagitis are at risk of developing complications. The therapeutic
      goals in GORD are symptom relief, healing of lesions, prevention of
      complications, and omittance of adverse effects at the lowest possible costs.
      Patients with functional dyspepsia usually have symptoms of less severe intensity
      and as, per definition, no organic substrate is demonstrable, complications do
      not develop in these patients. Therefore, in patients with GORD and functional
      dyspepsia, treatment of GORD should have the highest priority. Pharmacologic
      treatment of GORD comprises H2 receptor antagonists, proton-pump inhibitors and
      cisapride. The pharmacologic treatment of functional dyspepsia is less documented
      and in most studies the symptomatic pattern could not predict the pharmacologic
      principle of clinical benefit. This may be because a separation between presence
      of symptoms and presence of symptoms as a major problem has not been taken into
      account. Cisapride is the drug that has been proven clinically useful in most
      randomized studies. This does not, however, rule out that other drugs are better
      in subgroups of patients with functional dyspepsia.

PMID- 8545628
TI  - Gastro-oesophageal reflux and chronic respiratory disease in infants and
      children: treatment with cisapride.
AB  - Gastro-oesophageal reflux (GOR) has been implicated in such clinical phenomena as
      aspiration pneumonia, bronchospasm or wheezing, apnea, stridor, and hoarseness.
      Various tests have been used as an aid to diagnosing patients with chronic
      respiratory disease where GOR is a causal factor. Different forms of conservative
      treatment have been tried for GOR, including cisapride. Several studies have
      evaluated its effect on the pH profile and respiratory symptoms in patients with
      chronic respiratory disease and have demonstrated improvement of nocturnal
      wheezing, cough, and irritability. Our experience with cisapride is positive in
      children with GOR. Patients refractory to medical treatment have been surgically
      treated with good results.

PMID- 8545629
TI  - Gastro-oesophageal reflux disease in general practice.
AB  - Symptoms of reflux-like dyspepsia and gastro-oesophageal reflux disease (GORD)
      are common problems in the community and in general practice. The 1-year
      prevalence of reflux-like dyspepsia is in the region of 30%, with many patients
      experiencing a range of other symptoms in addition to the principal complaint of
      retrosternal pain or burning. Although only a minority, about one-quarter, of
      these patients consult general practitioners about their problems, many of them
      have had symptoms for several years, and experience symptoms on a frequent, often
      daily, basis. The decision to consult a general practitioner often depends more
      upon patients' anxieties about the possibility of heart disease and cancer than
      on symptom severity. General practitioners need to address these issues, as well
      as attempting to make a safe, clinical diagnosis; this is aided by the findings
      that, at least in patients under the age of about 45, a reasonably confident
      clinical diagnosis can be made on the basis of symptoms alone, although older
      patients and those in whom alarm symptoms are present require timely
      investigation. The increasing availability of open-access endoscopy means that
      many of these patients can be managed entirely in general practice without the
      need for specialist referral. Management in general practice begins with a clear
      explanation of the mechanisms and significance of GORD and a direct response to
      patients' anxieties. Lifestyle factors may require modification before drug
      therapy begins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545630
TI  - The clinical use of cisapride in gastro-oesophageal reflux disease, with
      particular focus on the long-term treatment aspects.
AB  - BACKGROUND: The healing of oesophagitis, both symptomatic and endoscopic, can be
      obtained with cisapride, the results being equivalent to what has been achieved
      with H2RAs. For many patients, however, GORD is a chronic relapsing disease.
      RESULTS: At least 40-50% of patients relapse within a year of initial healing.
      Important predictors for relapse are the severity of symptoms, the degree of
      mucosal damage, and the time it takes for the initial lesions to heal. Another
      important predictor of relapse, as shown in the cisapride maintenance studies, is
      the need for PPIs, probably because the most recalcitrant patients were selected
      for this therapy. CONCLUSIONS: Patients with mild or moderate disease should be
      treated with intermittent or prolonged therapy with cisapride or H2RAs. Patients
      with severe disease should be given prolonged or permanent therapy with a PPI or
      with cisapride in combination with either an H2RA or a PPI. For the latter group,
      antireflux surgery should also be considered, especially in younger patients who
      have a completely incompetent closing mechanism of the lower oesophageal
      sphincter.

PMID- 8545631
TI  - The prevalence of gastro-oesophageal reflux disease.
AB  - Estimation of the prevalence of gastro-oesophageal reflux disease (GORD) is
      difficult because of the lack of an accepted definition and a gold standard.
      Based on the occurrence of reflux symptoms and on the use of antacids in the
      population, the prevalence of GORD may be estimated at about 10%. The 1-year
      incidence of endoscopic oesophagitis has been shown to be 1.2%. In an endoscopic
      population study, oesophagitis was found in about 10% of the adult population.
      However, the criteria used for the diagnosis were disputable. The true prevalence
      of oesophagitis is probably about 5%, higher in males than in females. The
      severity of GORD tends to increase with age, with regard to both symptoms and
      oesophagitis.

PMID- 8545632
TI  - The pathophysiology of gastro-oesophageal reflux disease: an overview.
AB  - Gastro-oesophageal reflux disease (GORD) is a multifactorial disease. Although it
      is primarily a motility disorder, several other disturbances can interfere and
      contribute to determine the severity of symptoms and the degree of lesions. In
      normal subjects, as in patients with pathological reflux, nearly all the episodes
      of reflux obey one of the following three mechanisms: (a) a transient complete
      relaxation of the lower oesophageal sphincter (TLOSR), (b) a transient increase
      in intra-abdominal pressure which overcomes the resistance of the antireflux
      barrier ('stress reflux') and, (c) a spontaneous reflux through a permanently
      hypotonic sphincter. Gastric distension is the major factor that can induce
      TLOSRs. Whereas, at rest, the diaphragm probably plays little role in cardial
      competence, diaphragmatic contraction may help prevent reflux in conditions
      resulting in increased abdominal pressure such as during physical activity and
      abdominal staining. The presence of a hiatal hernia increases susceptibility to
      reflux. A delayed gastric emptying may also facilitate reflux and represents a
      factor of resistance to antireflux therapy. Most studies in humans have shown
      that motor abnormalities remain unchanged after healing of oesophagitis. Acid and
      pepsin are the most noxious agents of the upper gastrointestinal secretions that
      can participate in the pathogenesis of oesophagitis. However, there is no
      evidence that patients with reflux have greater acid secretion than subjects
      without reflux. The clearance function is a two-stage phenomenon requiring first
      a reduction in volume by peristalsis and then chemical neutralization by saliva.
      Primary peristalsis is mainly responsible for the clearance of acid in both the
      upright and the supine positions. It takes longer to clear acid in patients with
      non-reducing hiatal hernia. The layer of mucus which carpets the mucosa comes
      from the saliva and also from the submucosal glands of the oesophagus. The
      paracellular pathway is the major route by which mucosal HCl enters and then
      damages the oesophageal epithelium. Only a minority of acid reflux episodes are
      accompanied by symptoms. The acid exposure during the time period that precedes a
      reflux episode (i.e. the acid burden) is a key factor determining whether that
      reflux episode will be symptomatic or asymptomatic.

PMID- 8545633
TI  - Can we prevent tarnishing a gold standard?

PMID- 8545634
TI  - Role of nuclear medicine in evaluating patients with suspected gastrointestinal
      motility disorders.
AB  - Functional symptoms caused by gastrointestinal motility disorders are relatively
      common in the general population. Knowledge of the relationship between symptoms
      and the underlying gastrointestinal dysmotility provides physicians with a
      framework for successful evaluation and treatment of patients with possible motor
      disorders of the gastrointestinal tract. Scintigraphy provides for noninvasive
      and quantitative assessment of physiological transit throughout the
      gastrointestinal tract, and it is extremely useful for diagnosing
      gastrointestinal motor dysfunction. The wide range of scintigraphic studies now
      available supplement other diagnostic tests for evaluation of all segments of the
      gastrointestinal tract.

PMID- 8545635
TI  - Esophageal transit scintigraphy.
AB  - Esophageal transit scintigraphy was introduced over 20 years ago, but its exact
      role in the evaluation of patients with suspected esophageal motility disorders
      still remains controversial. The experience with this test supplies clues, if not
      answers, for the following key questions: "When is it useful?", "How should it be
      performed?", and "Are there different methods for different applications?"
      Opinions vary, but it seems at the very least to be useful clinically under the
      following conditions: (1) when esophageal manometry is unavailable or not
      tolerated, (2) when manometry is equivocal or negative but a reasonable suspicion
      of disease remains, and (3) when clinical management will be aided by monitoring
      for serial change or response to therapy.

PMID- 8545636
TI  - Recent advances in gastric emptying scintigraphy.
AB  - Gastric emptying scintigraphy was introduced more than 25 years ago by Griffith
      and still remains the gold standard to assess gastric emptying. Test meals,
      radiopharmaceutical and acquisition procedures have been refined and optimized
      over the years and the test procedure is now well standardized. However, in its
      most common use, gastric emptying scintigraphy provides little information on
      gastric physiology and pathophysiology. Over the last decade, modeling of the
      liquid- and solid-emptying curves has provided some insight into the complex
      gastric physiology. Compartmental analysis of the stomach has also provided
      information on the pathophysiological mechanisms of delayed gastric emptying.
      Over the past 5 years, the most dramatic development in gastric emptying
      scintigraphy has been the introduction of digital antral scintigraphy. Digital
      antral scintigraphy consists primarily of dynamic imaging of the stomach and a
      refined Fourier transform processing method. This new procedure allows for the
      visualization of antral contractions and, like manometry, permits quantitative
      characterization of the frequency and amplitude of these contractions. Overall,
      this new procedure provides a unique, noninvasive tool to characterize gastric
      motility, to define the pathophysiological mechanisms of gastric motor disorders,
      and to evaluate the effect of new gastrokinetic compounds.

PMID- 8545637
TI  - Whole-gut transit scintigraphy in the evaluation of small-bowel and colon transit
      disorders.
AB  - Scintigraphic methods for performing gastric emptying and colon transit studies
      are now well standardized. Although not as well established, several methods have
      been proposed for measuring small-bowel transit. The measurement of orocecal
      transit time appears to be a practical scintigraphic measurement of small-bowel
      transit. When combined into a single test of gastric emptying, small-bowel, and
      colon transit, whole-gut transit scintigraphy is an important, noninvasive tool
      for documenting dysmotility of any segment of the gastrointestinal tract. Despite
      attempts to simplify the study, whole-gut transit scintigraphy still requires a
      significant commitment of time and equipment. As with other gastrointestinal
      studies, each laboratory must determine which protocol best fits its clinical
      needs, equipment, and staffing. Attention must be paid to adhere to established
      protocols, or normal values will need to be determined for each laboratory.
      Despite these difficulties, whole-gut transit scintigraphy now represents an
      important clinical tool for the evaluation of patients with a wide range of
      abdominal complaints.

PMID- 8545638
TI  - Pediatric gastrointestinal motility studies.
AB  - Radionuclide studies for evaluating gastrointestinal transit in adults have been
      adapted for use in infants and children for assessing esophageal transit,
      gastroesophageal reflux, and gastric emptying. However, the measurement of small-
      and large-bowel transit times in these patients has been limited.

PMID- 8545639
TI  - Right ventricular 201T1 uptake on myocardial perfusion single photon emission
      computed tomography imaging.

PMID- 8545640
TI  - Extraosseous uptake of 99mtechnetium phosphate in an extremity.

PMID- 8545641
TI  - CT/MRI of musculoskeletal complications of AIDS.
AB  - While uncommon, many musculoskeletal disorders may be seen in association with
      the acquired immune deficiency syndrome (AIDS). Infections such as osteomyelitis,
      bacterial myositis and septic arthritis, neoplasms such as non-Hodgkin lymphoma
      and Kaposi sarcoma, and myopathies and polymyositis have been reported in this
      patient population. Computed tomography and magnetic resonance imaging frequently
      detect unanticipated musculoskeletal disease in a patient with AIDS, and may
      further help to distinguish infections from neoplastic disorders.

PMID- 8545642
TI  - Association between diffuse idiopathic skeletal hyperostosis and multiple
      myeloma.
AB  - OBJECTIVE: To determine whether an association exists between multiple myeloma
      and diffuse idiopathic skeletal hyperostosis (DISH). DESIGN AND PATIENTS:
      Radiologic studies were performed over a 26-month period in a series of 97
      consecutive patients with multiple myeloma (56 male and 41 female, aged 42-91
      years). RESULTS: Both myelomatous bone lesions and hyperostosis similar to DISH
      were found in these patients. The prevalence of DISH in association with multiple
      myeloma (21 male and 8 females patients) was higher (29.8%) than in our control
      group (973 patients, 449 male and 524 female) or in the general population (15
      20%). The involved segments of the column were thoracic in 11 males and 7
      females, cervical in 8 males and 2 females, and lumbar in 5 males and 4 females.
      Ossifying enthesopathy in the pelvis ("whiskering") was observed in 7 males and 1
      female. CONCLUSIONS: The pathogenesis of hyperostosis remains unknown. It is
      possible that the coexistence of DISH and multiple myeloma is merely an
      association. For this reason, it is important for the real prevalence of DISH in
      the general population to be defined.

PMID- 8545643
TI  - Intravenous methylmethacrylate following cemented total hip arthroplasty.
AB  - Both cemented and noncemented techniques have been used for total hip
      arthroplasty (THA). Each technique has advantages and disadvantages. Among the
      disadvantages of cemented THA are several perioperative complications, such as
      intraoperative cardiac or respiratory failure and hypotension, called "cement
      implantation syndrome," and extrusion of cement beyond the confines of the
      medullary canal. Cement extrusion can be the result of overreaming of the femoral
      canal and cortical perforation. This is a worrisome finding, as the risk of
      subsequent femoral fracture at the site of perforation is increased. Extruded
      cement, however, does not always indicate a problem. Extruded cement located
      within the femoral venous system, intravenous methylmethacrylate, for example, is
      not associated with long-term complications. While uncommon, it is important to
      differentiate this finding from the more serious cortical perforation. We report
      four examples of intravenous methylmethacrylate following THA and describe the
      imaging features that allow differentiation of this entity from the more
      significant finding of cortical perforation.

PMID- 8545644
TI  - Effect of field of view on MR diagnosis of rotator cuff tears.
AB  - PURPOSE: To determine the effect of decreasing the field of view (FOV) on the
      accuracy of MR for diagnosing rotator cuff tears. MATERIAL AND METHODS: One
      hundred shoulder MR scans with surgical correlation were evaluated for the
      presence or absence of a cuff tear. The sensitivity and specificity of MR
      relative to the surgical results were determined for the 59 patients scanned with
      a 24-cm FOV, and the 41 patients scanned with an 18-cm FOV. All other imaging
      parameters including acquisition time were identical. The sensitivity and
      specificity of the two groups were compared using a t-test. RESULTS: The
      specificity of MR for diagnosing a rotator cuff tear improved from 0.65 for the
      24-cm FOV group to 0.89 for the 18-cm FOV group (P = 0.04). The sensitivity
      changed from 0.91 to 0.96 (P = 0.25). CONCLUSION: Reducing the FOV from 24 cm to
      18 cm results in a statistically significant improvement in specificity of MR for
      diagnosing rotator cuff tears.

PMID- 8545645
TI  - Musculoskeletal melioidosis: clinical and imaging features.
AB  - OBJECTIVE: Melioidosis is a tropical infection caused by a gram-negative
      bacillus, Pseudomonas pseudomallei. The disease manifests initially as localized
      suppurative lesions and can progress to acute disseminated septicemia with 65-90%
      mortality if inadequately treated. Musculoskeletal involvement is common. The
      purpose of this study was to describe the clinical features and imaging
      appearances of musculoskeletal melioidosis. DESIGN: We retrospectively analyzed
      the clinical profiles and images of 26 patients diagnosed over a 6-year period as
      suffering from melioidosis. PATIENTS: The study group comprised 11 patients with
      musculoskeletal melioidosis and 15 patients with nonmusculoskeletal melioidosis.
      RESULTS AND CONCLUSIONS: We found that musculoskeletal melioidosis mimicks other
      infections both clinically and radiologically. Clinical awareness is therefore
      crucial, as diagnosis can only be established by bacteriological and
      immunological studies. Prompt treatment with long-term combination antibiotics in
      high dosages and surgical drainage of abscesses improves survival.

PMID- 8545646
TI  - CT determination of tibial tubercle lateralization in patients presenting with
      anterior knee pain.
AB  - Anterior knee pain is commonly associated with patellofemoral malalignment. Both
      conventional radiographic measurements and CT measurements have been proposed to
      define and confirm the sometimes difficult clinical diagnosis of anterior knee
      pain secondary to patellofemoral malalignment. Using CT imaging with computerized
      technique to measure anatomic relationships, we evaluated patients (n = 50) with
      anterior knee pain for excessive lateralization of the tibial tubercle. The
      symptomatic knee of each patient was compared with their asymptomatic knee as
      well as with the knees of patients with other causes of anterior knee pain (n =
      10) and with the knees of asymptomatic controls (n = 10). The symptomatic knee of
      patients with suspected patellofemoral malalignment demonstrated significantly
      greater lateralization of the tibial tubercle (12.2 +/- 0.5 mm) than did the
      asymptomatic knee (9.0 +/- 0.7 mm). The symptomatic knees of patients with
      patellofemoral malalignment also demonstrated significantly greater
      lateralization of the tibial tubercle than did the knees of patients with other
      causes of anterior knee pain (5.9 +/- 0.9 mm). When a control population was
      added to the analysis, the patients with symptomatic patellofemoral malalignment
      demonstrated significantly greater lateralization of the tibial tubercle than did
      the controls (6.4 +/- 0.4 mm). Using a critical value of 9 mm lateralization, the
      CT diagnosis of patellofemoral malalignment had a specificity of 95% and a
      sensitivity of 85%. We conclude that CT determination of tibial tubercle position
      assists the diagnosis of patellofemoral malalignment.

PMID- 8545647
TI  - Diagnosis of popliteus injuries with MR imaging.
AB  - OBJECTIVE: Popliteal muscle and tendon injuries are thought to be unusual. This
      report describes the magnetic resonance (MR) appearances of popliteus muscle and
      tendon injuries. DESIGN AND PATIENTS: The study included 24 patients where the
      diagnoses of popliteal injuries were prospectively made based on MR appearances.
      The study group was taken from 2412 consecutive knee MRIs. The injuries were
      characterized as to involving the muscular or tendinous portions of the popliteus
      apparatus. RESULTS: In 95.8% (23/24) of patients, the tears of the popliteus
      involved the muscular portion. The injuries were either partial and interstitial
      or complete. Three patients had tears of both the muscular and tendinous portions
      or the tendon alone. The anterior and posterior cruciate ligaments were torn in
      16.7% (4/24) and 29.2% (7/24) of patients, respectively. There were medial and
      lateral meniscal tears in 45.8% (11/24) and 25% (6/24) of patients, respectively.
      There were injuries of the medial and lateral collateral ligaments in 8.3% (2/24)
      and 4.2% (1/24) of patients, respectively. Bone bruises and/or fractures were
      seen in 33.3% (8/24) patients. In 8.3% (2/24) of patients, the popliteus injury
      was an isolated finding. CONCLUSION: Popliteus muscle and tendon injuries are not
      uncommon. They usually occur in conjunction with other significant injuries of
      the knee and can be characterized with MR imaging.

PMID- 8545648
TI  - MRI of the Stener lesion.
AB  - OBJECTIVE: To assess the utility of MR in detecting surgically induced Stener
      lesions (displaced thumb ulnar collateral ligaments) in cadaveric models. DESIGN:
      Six cadaver thumbs had ulnar collateral ligament (UCL) tears created surgically.
      MR examinations (2D STIR and 3D GRASS) were performed identically on all
      specimens both before displacement (non-Stener) and after displacement (Stener
      lesion) of the UCL. The MR images were then randomly numbered. Each image was
      evaluated separately in blinded fashion by four musculoskeletal radiologists for
      the presence or absence of a Stener lesion. Each radiologist reinterpreted the
      images after an interval of several days. The interpretation was based on
      previously published criteria for Stener lesion diagnosis by MR. RESULTS: The
      sensitivity of GRASS ranged from 0.17 to 0.67 with the most experienced reader
      scoring the lowest. The specificity of GRASS ranged from 0.33 to 1.0 (most
      experienced reader 0.67, 0.83). STIR had a sensitivity of 0.00-0.17 and a
      specificity of 0.53-0.83. The kappa values for inter- and intraobserver agreement
      were measured. The intraobserver kappa for GRASS was 0.27-0.75 (most experienced
      reader 0.75). CONCLUSIONS: 2D imaging is probably inadequate for the evaluation
      of Stener lesions. The most likely reason is that the STIR slice thickness of 3
      mm limits resolution of small UCLs. The poor sensitivity and specificity of GRASS
      as well as poor interobserver agreement suggest that MR may not be sufficiently
      accurate for Stener lesion evaluation.

PMID- 8545649
TI  - Bupivicaine arthrography of the post-arthroplasty hip.
AB  - Addition of bupivicaine, a medium-length-acting local anesthetic, to the contrast
      material in arthrography of total hip prostheses provides reliable information as
      to whether the source of pain is intracapsular or extracapsular. In 12 surgically
      proven cases, complete relief of pain after bupivicaine injection correctly
      identified an intracapsular source of pain in 10, with only 1 false-positive and
      1 false-negative. These results compare favorably with the results of the
      contrast arthrograms in these patients in localizing the pain even if a specific
      diagnosis could not be reached. Bupivicaine as an adjunct to contrast material
      during arthrography provides additional information useful in management
      decisions regarding the necessity of revision arthroplasty.

PMID- 8545650
TI  - Degenerative changes of the trapeziometacarpal joint: radiologic assessment.
AB  - The trapeziometacarpal joint is particularly prone to osteoarthritis due to the
      great amount of stress applied with everyday activities with the hands. In this
      essay, radiologic assessment and staging of "basal joint" osteoarthritis,
      treatments based on radiologic staging and intraoperative findings, and surgical
      complications are described.

PMID- 8545651
TI  - Bone densitometry.

PMID- 8545652
TI  - High-grade surface osteosarcoma of the humerus.
AB  - We presented a case of high-grade surface osteosarcoma of the humerus in a 12
      year-old girl and the results of our analysis of 26 cases reported in the
      literature. Twelve of the 21 patients for whom substantial follow-up information
      was reported had died of the disease, and the results of the analysis regarding
      the efficacy of chemotherapy and medullary involvement were ambiguous. It is
      emphasized that high-grade surface osteosarcoma is a distinct entity, since it is
      associated with a poorer prognosis than other osteosarcomas arising on the
      surface of bone.

PMID- 8545653
TI  - Muscular sarcoidosis.
AB  - A 57-year-old woman with sarcoid nodules in muscles of the lower leg was
      reported. A star-shaped low signal intensity in the lesion on MR imaging,
      supposedly corresponding to fibrous scar, appears characteristic of this
      condition, although its specificity is still uncertain.

PMID- 8545654
TI  - Intramuscular ossified hemangioma.

PMID- 8545655
TI  - Subperiosteal ganglionic cyst of the iliac wing.

PMID- 8545656
TI  - MR imaging of a meniscal ossicle.
AB  - We report the MR appearance of a meniscal ossicle, which is an unusual etiology
      for knee pain. The role of MR in differentiating a meniscal ossicle from a loose
      body is presented. The MR images also demonstrated associated tibial cartilage
      thinning and a possible meniscal tear. These MR findings led to arthroscopic
      treatment rather than conservative management. A review of the literature on
      meniscal ossicles is also presented.

PMID- 8545658
TI  - Osteoid osteoma of the mastoid tip.

PMID- 8545657
TI  - Giant bone island of femur. Case report, literature review, and its distinction
      from low grade osteosarcoma.
AB  - A 42-year old male with the largest reported giant bone island (10.5 cm in
      length) is presented. Due to its ominous size, association with some degree of
      pain and increased uptake on radionuclide bone scan, a biopsy was considered
      necessary definitively to rule out a slow-growing osteosarcoma or blastic
      metastasis. Documentation of growth in adult patients of conventional and giant
      bone islands, coupled with evidence of increased radionuclide uptake, makes the
      clinicoradiological distinction between bone islands and blastic malignancies
      difficult. Guidelines for biopsy versus serial radiographic follow-up of such
      lesions are addressed.

PMID- 8545659
TI  - Adamantinoma.
AB  - This is an unusual case of an adamantinoma in an early phase of evolution. It was
      much smaller than adamantinomas typically seen at presentation, although it was
      located in the usual anterior tibial cortical region. Slow growth and a prolonged
      period of symptoms are common with adamantinoma and were also observed in this
      patient. The multifocal presentation within the same bone is unusual. This case
      illustrated the need to consider adamantinoma in the differential diagnosis of
      any pre-tibial cortical lesion despite the small size, benign presentation, or
      the longevity of symptoms.

PMID- 8545660
TI  - Solitary cystic lymphangioma.
AB  - A young girl had a large isolated and localized multicystic lesion of the right
      humerus, which was revealed by a pathological fracture. MRI and bone biopsy
      showed liquid-filled bone cysts. The final diagnosis was localized cystic
      lymphangiomatosis.

PMID- 8545661
TI  - Fibrolipomatous hamartoma of the radial nerve: MR imaging findings.

PMID- 8545662
TI  - The subjective experience of health and illness in Ocuituco: a case study.
AB  - This sociological study aims to understand the subjective experience of health
      and illness of the inhabitants of Ocuituco (Mexico). This interpretation is made
      in connection with the social and subjective contexts of this town. Four factors
      characterize Ocuituco's social context: (1) economic deprivation (poverty); (2)
      male domination (patriarchy); (3) a process of medicalization; and (4) a decline
      of traditional medicine. Ocuitucans view their world (subjective context) with:
      (1) a sense of being exploited; (2) a sense of being at the bottom of the social
      scale; (3) a sense of uncertainty; (4) a familiarity with a patriarchal and
      violent order; (5) the negative view that individuals have of themselves; and (6)
      a sense of change in the community. The literature review differentiates between
      normative and interpretive sociological approaches. The analysis is based on 74
      in-depth interviews with women and men, conducted in two stages (1988 and 1992).
      Individuals' accounts constitute a double indicator: they express individuals'
      subjective experience of health and illness while at the same time they also
      index the social order of which they are a product. The analysis comprises both
      the concept and the experience of health and illness. An analysis is made on the
      subjective experience of symptoms and causes of disease. The main findings refer
      to the parallel between individuals' general view of the world (subjective
      context) and their view of health and illness. Ocuitucans perceive health as an
      unlikely achievement in a world full of constraints. This is linked to the
      existence of elaborated conceptualizations of health in this town. The notion of
      strength is central in the subjective experience of illness.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8545663
TI  - Ethnic differences in contraceptive use in Kuwait: a clinic-based study.
AB  - The Arab, Muslim, oil-rich nation of Kuwait has achieved unusually high levels of
      knowledge and use of contraception for a developing, high fertility country.
      Almost all women know of contraceptive pills without prompting, and 57-86% report
      having ever used a method (usually the oral pill or IUD) in recent studies. Based
      on a survey of six randomly selected clinics the present study compares the
      knowledge and use levels of two major ethnic groups--the Beduins and non-Beduins.
      It also analyses preference for various contraceptive methods and probable
      reasons for this. While Census or Survey data do not provide information about
      the size of ethnic groups analyzed in this paper, it is estimated that at least
      one-third of the population of Kuwait is Beduin. There is a significant
      difference between the levels of knowledge and use of contraception between the
      Beduin and non-Beduin women; current use being 42% and 65%, respectively. The
      differentials between the two groups are particularly marked among women of lower
      socioeconomic status, and tend to reduce notably once variables such as education
      and income are controlled. Within the subgroup of non-Beduins, socioeconomic
      differences in contraceptive use have virtually disappeared; the illiterate and
      relatively less affluent women are as likely to use a contraceptive method as the
      university educated, and richer women. However, among the Beduins, the usually
      expected differences by socioeconomic characteristics still persist. The oral
      pill is the best known and most commonly used method. Male sterilization is the
      least known and not practiced at all.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545664
TI  - The impact of the Gulf armed conflict on the health and behaviour of Kuwaiti
      children.
AB  - This study deals with the psychological reactions of Kuwaiti children to war
      related stresses in the early period of the Gulf crisis following the summer 1990
      Iraqi invasion of Kuwait. A sample of 106 children was drawn from Kuwaiti
      displaced families and a comparable control sample was obtained from Saudi
      families in Riyadh, Saudi Arabia. An interview checklist of symptoms of physical
      and psychological distress was administered to the index child and a female key
      informant in each household of cases and controls. Most Kuwaiti children were
      exposed to unpleasant war experiences. It was found that Kuwaiti children
      exhibited a substantially greater degree of dysfunctional social and emotional
      behaviour. The types of adverse behaviours were a function of the child's age,
      sex and experience of aggression. The findings support the notion that a negative
      relationship exists between armed conflict and the health and behaviour of the
      children. The complex needs of children exposed to violence require professionals
      to seek ways of combining psychodynamic interventions and relief programmes.

PMID- 8545665
TI  - Epidemiology's role in the creation of a humane world: convergences and
      divergences among the schools.

PMID- 8545666
TI  - Psychosocial and behavioral factors associated with serum lipids in university
      students.
AB  - The impact of psychosocial and behavioral factors on serum lipids was examined in
      46 male and 47 female students with a mean age of 23 years. Subjects were
      recruited from the University of Stockholm and the study was performed with the
      Student Health Care Organization in order to have a basis for intervention
      programs. Significant associations between serum lipids and parental education,
      regularity of breakfast habits, nourishing eating, social support, depressive
      feelings and quality of life are found. However, there is no consistent pattern
      for these associations in men and women. Thus, some associations are significant
      for men and some for women. Women with parents having higher levels of education
      had lower values of cholesterol, triglycerides and apo B, and higher values of
      apo A-1 (representing the 'good' cholesterol) than women whose parents were not
      highly educated. When controlling the associations for confounding factors such
      as age, body mass index, physical activity, coffee, alcohol, smoking habits,
      nourishing eating and quality of life, the associations were strongly confirmed.
      No similar associations were found in men. Men who reported low social support or
      social integration and a low perceived quality of life showed a tendency to
      higher levels of lipids compared to those who reported high integration and
      quality of life. Regularity of dietary habits was found to be associated to serum
      lipids in men, the greater the regularity, the lower the lipid levels. The
      strongest association was found for regularity of breakfast habits. This
      association was also strongly significant in the regression analysis after
      controlling for the described confounding factors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8545667
TI  - Explaining rising mortality among men in eastern Europe.
AB  - Since the mid-1960s, rates of premature mortality have increased among men in all
      Eastern European countries, giving rise to an East-West health divide. The paper
      examines the existing data concerning the possible role of levels of smoking,
      fats consumption and/or environmental factors in explaining this phenomenon. An
      overview is offered of the key ways in which social experience in Eastern Europe
      has diverged from that in the West and it is argued that such an overview is pre
      requisite for understanding the deteriorating health of men in the East. The
      importance of the 'incongruity' between aspirations and the means of achieving
      them is highlighted, as is the centrality of family-based coping strategies. It
      is argued that the devaluing of the public sphere and valorization of the private
      domain contribute to the greater health vulnerability of men under in Eastern
      Europe. The importance of the private sphere is reflected in the fact that the
      rise of premature male mortality has been overwhelmingly concentrated in the non
      married population in the East European countries for which data is currently
      available.

PMID- 8545668
TI  - Gender differences in the relationship between social network support and
      mortality: a longitudinal study of an elderly cohort.
AB  - Despite well-recognized gender differences in patterns of social network support,
      few studies have explored whether the pathways by which social support affects
      mortality risk differ for men and women. In a 15-year follow-up study of elderly
      HMO members, we found that network size affected men's mortality risk indirectly,
      through their health status, while no such indirect effect was found for women.
      The data also suggested that network size had a direct protective effect on
      mortality risk for both men and women, with men gaining protection at a lower
      level of network size than women. These findings confirm the need for a gender
      specific approach to further research on this subject, and suggest the need to
      measure variables that capture the different meaning and value of social network
      participation for men and women.

PMID- 8545669
TI  - [Homogeneity of the spatial distribution of cancers of the female reproductive
      tract in Quebec].
AB  - Risk factors associated with women's reproductive life and sexual growth do not
      adequately predict cancer incidence of the breast, uterus and ovary. The
      heterogeneous worldwide distribution of these cancers could imply that some
      environmental and cultural risk factors are involved in their cancerogenesis. The
      few attempts made so far to unravel their spatial structures at a geographic
      scale facilitating the search for exogenous risk factors have proved
      inconclusive. This study reports the results of a spatial analysis of the cancer
      incidence rates for breast, cervix, endometrium and ovary among Community Health
      Departments (CHD) in Quebec using a spatial autocorrelation method. Correlograms
      built according to four definitions of the inter-CHDs distance indicate that
      breast and ovary incidence rates follow quite similar spatial gradients attesting
      to their etiologic affinity. They also suggest that the spatial distribution of
      endometrial cancer follows a gradient divergent from that of breast and ovary
      cancers, and that the CHDs' spatial scale does not suitably describe the
      distribution of cervical cancer. The demonstration of a structured spatial
      distribution for breast, endometrium and ovary cancers in Quebec strengthen the
      hypothesis that cultural or environmental risk factors are involved in their
      etiology. But, the observed disparities in the spatial structure of these cancers
      imply that their etiologic specificity may be greater than their biologic bond
      would suggest.

PMID- 8545670
TI  - Sewers and scapegoats: spatial metaphors of smallpox in nineteenth century San
      Francisco.
AB  - Medical geography is slowly including more social and cultural theory in its
      analysis of health issues. Yet there is still room for theoretical growth in the
      discipline, in areas such as historical inquiry, metaphoric landscapes of
      disease, and the role of disease and its interpretations in the production of
      place. With the example of four smallpox epidemics in nineteenth century San
      Francisco, application of these concepts is illustrated. Each successive epidemic
      in San Francisco brought stronger association of the disease with Chinatown,
      until an almost complete metonymy of place and disease had occurred by the last
      decades of the century. The articulation of biased medical theory onto a
      landscape of xenophobia engendered this metaphorical transformation of Chinatown
      into a pustule of contagion threatening to infect the rest of the urban body. A
      less metaphoric mapping of smallpox focused on the sewer. According to 19th
      century miasmatic theories of epidemiology, sewers were the most dangerous urban
      topographical feature. In an increasingly class-stratified city, they undercut
      attempts of the upper classes to escape disease by carrying smallpox-causing
      miasmas across class and ethnic boundaries. A reinvigorated sanitation movement
      was the result. Both reactions to smallpox epidemics had significant influence in
      shaping San Francisco's landscape, real and symbolic.

PMID- 8545671
TI  - Process and outcomes in general practice consultations: problems in defining high
      quality care.
AB  - In order to explore the relationships between the verbal interactions of the
      consultation and several outcomes (patient health change, patient compliance and
      the satisfaction of both doctor and patient), 21 General Practitioners
      contributed ten audiotaped consultations each, from consecutive consenting adult
      patients. The effects of GP sex and postgraduate training were also investigated,
      but were found to be minimal. Patient health change was most clearly related to
      acuteness of symptoms at presentation, whereas reported compliance was predicted
      by patient satisfaction after the consultation. Different consultations were
      maximally satisfying for doctors and for patients, and patient and doctor
      satisfaction with specific consultations showed little correlation. This result
      implies that the measurement of quality of care, in general practice at least, is
      a more complex task than has been assumed, and in turn raises issues about whose
      definition of outcome is relevant in discussing quality of care.

PMID- 8545672
TI  - Public health problems of urbanization.
AB  - Developing countries have been peasant societies. The cities in traditional
      societies have been pilgrimage centres, seats of administration and educational
      centres. These cities had homogeneous relationships with the villages.
      Industrialization has developed modern megacities whose way of life is
      heterogeneous with that in the villages. Rural poverty has pushed villagers to
      the cities, which were never planned to accommodate immigrants. Public health and
      social problems have arisen lowering the quality of life. Communicable diseases
      among the urban poor coexist with non-communicable diseases among the
      comparatively affluent. Problems of pollution, crime and chronic morbidity
      increase. The NGOs provide relief to the poor and needy but do nothing toward
      creating an infrastructure for balanced development. The election of women as a
      result of non-discriminatory legislation provides good ground for hope.

PMID- 8545673
TI  - Elderly mental health in the developing world.
AB  - Growing numbers of elderly in countries of the developing world presage an
      increase in those affected by organic, age-related mental diseases such as
      dementia. A simultaneous rise in the burden of non-organic mental disorders in
      elderly populations is likely because stressors in many countries are affecting
      the mental health of the elderly directly and/or indirectly by altering the
      ability of families to provide care for them. This paper reviews studies on the
      disease burden of mental health problems of the aged in the developing world. It
      examines evidence on how demographic change, economic change, education,
      urbanization, war and displacement, and widowhood influence elderly mental
      health. A look at policies and programs improving the condition of elderly
      mentally ill throughout the developing world emphasizes positive options for
      policymakers. Recommendations for future research both identify areas in which
      investigation would be particularly useful and highlight current methodological
      problems.

PMID- 8545674
TI  - A better way of approaching adolescent pregnancy.

PMID- 8545675
TI  - Sociological dimensions of illness behavior.
AB  - The almost exclusive dependence on the diagnostic disease model limits addressing
      the burden of illness and disability typically seen in primary medical care. With
      aging of populations and increasing prevalence of chronic disease and disability
      and behavioral disorders, new approaches to patient assessment and intervention
      are needed to extend traditional models. Using illness behavior as a point of
      departure, I examine the disability process and the types of considerations
      relevant to promoting function and maintaining patients' quality of life. At the
      individual level, alternatives include modifying impairments, increasing patient
      motivation and encouraging helpful attitudes, teaching coping strategies,
      identifying helpful assistive devices, educating family members and employers and
      providing support. A broader view also makes clear that varying aspects of the
      disability process are appropriate issues for social policy and environmental
      remediation. In examining various examples of the disability process, the paper
      focuses on self-appraisal and illness behavior and the way social movements help
      to define and redefine conceptions of illness and disability. Recognizing that
      the kinds of changes discussed will not come easily, the paper concludes with a
      discussion of trends encouraging broader practice orientations and the types of
      interventions that can be helpful in encouraging and reinforcing such
      developments.

PMID- 8545676
TI  - The tooth as a marker of developing world quality of life: a field study in
      Guatemala.
AB  - A geographical sample in a rural area of eastern Guatemala revealed widespread,
      premature and heavy losses of permanent teeth. Social and environmental
      influences that affect tooth loss include inadequate diet, refined sugar, poor
      oral hygiene, absence of fluoride, lack of preventive education and insufficiency
      of dental care services. Land hunger and family poverty are of paramount
      importance. Gender-based cultural differences are apparent in tooth extraction
      rates, and use of dentures. No one escapes visitations of severe orofacial pain
      that cast a blight upon the quality of rural life. Periodontal disease drives the
      poorest of the poor to spend disproportionately large sums on pharmaceutical pain
      killers and destructive traditional medicines. Lay 'tooth-pullers' visit remote
      rural homes to extract teeth. Only full edentulism can bring patients permanent
      somatic and financial relief. Community dental health is conspicuously neglected
      in official policies and plans for rural development.

PMID- 8545677
TI  - Health promotion in primary care: physician-patient communication and decision
      making about prescription medications.
AB  - To examine health promotion in a primary-care context, we studied perceived and
      actual communication in 271 consultations between general practitioners and
      patients in Oxford (England). Although health promotion is a term usually
      reserved for public-health or wellness programs, a health promotion perspective
      enriches the examination of communication in physician-patient interactions by
      emphasizing issues of empowerment, competence and control. Accordingly, we are
      interested in how communication during medical encounters can improve patients'
      abilities to exercise appropriate control over their health. A major factor in
      enabling patients to increase control over their health involves developing their
      competencies for making decisions and enacting behaviors that can lead to
      desired, and attainable, health outcomes. This report focuses on communication
      and decision making about prescription medications, since whether and how to use
      medications are among the most common and important decisions in which patients
      can participate. Five instruments were employed to collect data about physicians,
      patients and their consultations: a Video Analysis, which allowed assessment of
      actual communication behavior; a Patient Questionnaire designed to gauge
      perceptions of the encounter and collect demographic information; a Medical
      Record Review, which provided information on utilization, diagnosis and
      treatment; a Telephone Interview, conducted 14 days after the consultation to
      obtain follow-up information (e.g. experience with the prescribed medication);
      and a Doctor Questionnaire that focused on attitudes toward consultations and
      patients. With respect to communication about prescription medications,
      physicians most frequently mentioned product name (78.2% of consultations) and
      instructions for use (86.7% of consultations). Patients were extremely passive,
      rarely offering their opinion or initiating discussion about any aspect of the
      treatment. We suggest that improving patients' decision-making competencies may
      require more discussion of benefits and risks, as well as discussion of patients'
      opinions about the prescribed medications and their abilities to follow through
      with the treatment plans. The research design proved useful in highlighting
      discrepancies between perceived and actual communication. Physicians tended to
      overestimate the extent to which they discussed patients' ability to follow the
      treatment plan, elicited patients' opinion about the prescribed medication and
      discussed risks of the medication. And, 24.3% of the patients left the
      consultation with an 'illusion of competence', a belief that important topics had
      been discussed when, in fact, they had not been mentioned at all. The pattern of
      results illustrates the complexity of health promotion in primary care, and
      underscores the importance of attending to both perceived and actual
      communication in medical encounters.

PMID- 8545678
TI  - Confiding in crisis: gender differences in pattern of confiding among cancer
      patients.
AB  - Social support has been identified as a key predictor of psychological morbidity
      following adverse life-events. However, the majority of the research has focused
      exclusively on women, despite evidence of significant gender difference in the
      utilisation and role of social support. To examine gender differences in patterns
      of confiding crisis, 520 subjects were interviewed within 8 weeks of a cancer
      diagnosis. Men were as likely as women to have confided their main concern in
      others (61% mainly or fully confided vs 67% of women, P = 0.308) but were much
      more likely to have used only one confidante (45% vs 25% of women, P < 0.001)
      while women made use of a wider circle of family, friends and partner and used
      more confidantes overall. The results confirm marked gender differences in the
      utilisation of social support at times of crisis and call into question the
      extent to which support research using exclusively female samples can be
      generalized.

PMID- 8545679
TI  - The cultural production of Bioterapia: psychic healing and the natural medicine
      movement in Slovakia.
AB  - Despite powerful opposition, natural medicine (NM) has achieved a toe-hold in the
      state-run biomedical system in the Slovak Republic. The physician-leader of the
      NM movement hopes to leverage his ministerial post as NM 'supreme expert' and his
      interlocking NM clinical and research facilities to achieve a complex, unified
      health care system under control of medical doctors. This health care model
      simultaneously reinforces biomedical hegemony and decenters classical medicine by
      substituting a bioenergetical paradigm. NM includes, among other diagnostic and
      healing modalities, acupuncture, herbal therapies, bee therapy, reflexology,
      iridology. However, its paradigmatic form is bioterapia, the focus of this paper.
      Bioterapia is a form of psychic healing or therapeutic touch. According to its
      practitioners, it is based on bioenergetic and information-processing principles.
      Conceptually, bioterapia unifies psyche, soma and energy dimensions of the human
      body and situates the human organism in an extended transpersonal social,
      physical and cosmological environment. Bioterapia is a scientized and medicalized
      reconstruction of a folk healing tradition whose appropriation simultaneously
      secularized and re-sacralized this tradition by re-locating its practice from lay
      healers to medical doctors, from the religious domain to the venerated scientific
      domain, from deviant science to normal science. The reconfiguration into
      bioterapia as part of the creation of an academic secular parapsychology in the
      former Soviet Bloc in the late 1960s, illustrates the use of the privileged
      discourse of science for a cultural production that seems to have both supported
      and subverted the regime.

PMID- 8545680
TI  - Reliability-adjusted disease maps.
AB  - Bayesian methods for adjusting mortality and morbidity rates to account for
      variations caused by small numbers are presented. Although such methods produce
      statistically biased morbidity and mortality rate estimates, these approaches are
      superior for any applications that depend on a relative ordering of a set of
      rates because the total error of prediction for the maps taken as a whole is
      smaller. This approach is especially relevant for identifying cancer 'hot spots'
      for a set of geographic areas. The theory and usefulness of making such
      adjustments for geographic data sets are described and an example presented,
      comparing classical and Bayesian rate estimation methods for rank ordering female
      breast cancer data in the San Francisco-Oakland SMSA.

PMID- 8545681
TI  - The ethics of discharge planning for older adults: an ethnographic analysis.
AB  - This paper uses ethnographic data to examine ethical dilemmas in discharging
      elderly persons from the hospital. The focus is on two elements significantly
      influencing that process, the patient's decisional capacity and the involvement
      of family members in decision-making. Within the field of bioethics these issues
      have been discussed in terms of factors compromising the autonomy of the patient
      and the interdependency of family members. An ethnographic analysis demonstrates
      how several assumptions in bioethical approaches to these issues are problematic.
      First, bioethical discussions generally neglect social and structural factors
      that condition discharge decision-making. The rationality and mental capability
      of the individuals making decisions are presumed to exist independently of those
      persons' social contexts; they are also assumed to be concrete properties
      amenable to objective assessment. Bioethical models further assume that 'the
      family' is an identifiable ontological unit that exists independently of the
      setting in which decisions are made and that interdependency is a concrete
      attribute of familial relations. In contrast, this study shows how discharge
      planning is an event produced by the interplay among diverse interests. The
      structure of the discharge planner's role and processes of collective decision
      making shape how medical staff perceive and define patients' decisional capacity
      and the involvement of families. This points to unintentional and unrecognized
      ways in which the patient's choices and control over decisions can be restricted.
      The analysis supports attempts to develop bioethical models based on socially
      grounded principles recognizing the importance of both autonomy and
      interdependence in long term care decisions.

PMID- 8545682
TI  - Pre-marital genetic counselling to consanguineous couples: attitudes, beliefs and
      decisions among counselled, noncounselled and unrelated couples in Israel.
AB  - Semi-structured interviews were conducted with 65 Israeli subjects who received
      genetic counselling while considering marriage to a close relative, 40 subjects
      married to a close relative who did not receive pre-marital genetic counselling,
      and 125 controls married to a nonrelative and never having considered marrying a
      relative. It was found that 72% of the consanguineous couples who received pre
      marital genetic counselling proceeded with their plans and married their
      relative; 86% of them reported that the counselling influenced their final
      decision to some degree. Counsellees' appraisals of genetic counselling revealed
      unfulfilled expectations to obtain more definitive answers, and mixed reactions
      to the nondirective approach applied by the counsellors. Comparisons between
      consanguineous and control couples revealed different views about consanguinity
      in general, and genetic risks in particular. Consanguineous couples, unlike
      controls, perceived consanguinity as an ordinary form of marriage, and had more
      favorable attitudes towards it. Compared to the noncounselled consanguineous
      group, consanguineous couples who received pre-marital genetic counselling had
      fewer children, estimated their genetic risk as lower but its subjective
      significance as higher, and perceived genetic disorders as more severe. The
      implications of these results are discussed from both theoretical and practical
      standpoints.

PMID- 8545684
TI  - The role of pharmaceuticals in the privatization process in Vietnam's health-care
      system.
AB  - The socialist republic of Vietnam had a centrally planned economy and a well
      distributed health-care system that was free to all. Since 1989 the government
      implemented a free market policy (Doi Moi). Authorities tried to shift part of
      the cost to users of health care and to improve aspects of the health-care system
      that appeared to be ineffective. Private practice of physicians and pharmacists
      was introduced in Vietnam. The introduction of privatization had consequences for
      the public health services at provincial, district, village and hamlet level.
      This has changed the character of the health-care system. Pharmaceuticals play an
      important role in the transactions between practitioners and patients, because
      they are the tangible goods that are exchanged in the transactions between users
      and providers of health care. Medical anthropologists interprete use and ideas on
      pharmaceuticals in terms of local cultural categories or as metonymic signs of
      technologically advanced societies from whence they come. Use of pharmaceuticals
      can also be understood in a historical and political context. This article
      describes pharmaceuticals in the process of privatization in Vietnam and the way
      they are seen by the Vietnamese in the context of political change. Their use
      carries meanings of medicines about transformations in political economy and as
      such this can be seen as a metaphor for the changing Vietnamese health-care
      system.

PMID- 8545683
TI  - Sexual communication in the age of AIDS: the construction of risk and trust among
      young adults.
AB  - Sexually transmitted diseases are extremely prevalent among youth, and it is only
      by understanding the processes involved in negotiating sexual relationships that
      effective prevention and intervention programs can be designed. This study
      explores sexual communication among young adults, how gender and sexual
      orientation influence negotiation for safer sex, the strategies employed for risk
      reduction, and the barrier to safer sex. It assumes sexual behavior as a
      communicative form, both reflective and reflexive, subject to interpretation, and
      created interactively within and between sexual partners. Data from in-depth
      interviews with 30 undergraduates at the University of California, Berkeley were
      triangulated with questionnaires (n = 159), secondary sources and informal
      interviews with university officials. Participants were representative of arts
      and science students, ethnically diverse and of varying sexual orientations.
      Interviews focused on the normative influences of family, school and friends
      regarding sexuality; and how relationships and sex were negotiated. They
      investigated how strategies for risk reduction, attitudes about HIV and testing,
      and contraceptive practices were managed differently by gender and sexual
      orientation and what the barriers to safer sex were in various situations.
      Interviews focused on the normative influences of family, school and friends
      regarding sexuality; how relationships were negotiated, and how trust and risk
      were constructed within relationships; how strategies for risk reduction,
      attitudes about HIV and testing, and contraceptive practices were managed
      differently be gender and sexual orientation; and what the barriers were to safer
      sex. Friends, the social culture at university, and the interaction of the two
      with the developmental tasks characteristic of the period between adolescence and
      adulthood were more important influences than parents or high school sex
      education classes in how sexual relationships were managed. How and whether
      friends talked about sex and practiced safe sex were strong normative influences
      in predicting safer sex among individuals. Negotiating for safer sex contains
      elements of impression management, requires assertiveness and takes constant
      effort, even among those who have made the most progress in incorporating it.
      Practicing safer sex involves a complicated process of sexual negotiation,
      requiring a degree of open communication about sexual desire and intent that is
      not widely available in this culture, and still less among young people. Risk and
      thus how sex is negotiated is assessed differently by gender, and varies further
      according to the degree of intimacy in the relationship or the sex act being
      contemplated. How sex is negotiated depends on the construction of risk and trust
      which differ by the type of relationship or sexual encounter being
      contemplated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8545685
TI  - Alzheimer's disease patients and their caregivers: medical care issues for the
      primary care physician.
AB  - Alzheimer's disease (AD) is a common problem with complex challenges in
      assessment and management for the primary care physician. We present a practical,
      six-step strategy for physicians to use in AD care, summarized by the acronym
      ACROSS: assessment of AD, communication of the diagnosis, referral to appropriate
      community resources, ongoing evaluation, providing solutions to patient and
      caregiver problems, and maintaining sensitivity to family caregiver issues. The
      family caregiver of the patient with AD provides the physician with essential
      diagnostic information and implements physician recommendations for AD care.
      Advice and support from the physician are essential for the family caregiver to
      withstand the relentless strain of caring for a loved one with a progressive
      dementia. We provide practical suggestions for management of common patient and
      caregiver problems across the stages of AD.

PMID- 8545686
TI  - Clinical and imaging features of pulmonary strongyloidiasis.
AB  - We evaluated 20 patients with pulmonary strongyloidiasis for risk factors,
      clinical and imaging manifestations, complications, treatment, and outcome.
      Eighteen (90%) had risk factors for strongyloidiasis including steroid use, age
      greater than 65, chronic lung disease, use of histamine blockers, or chronic
      debilitating illness. Pulmonary signs and symptoms, including cough, shortness of
      breath, wheezing, and hemoptysis, were present in 19 (95%); adult respiratory
      distress syndrome (ARDS) developed in 9 (45%). Pulmonary infiltrates occurred in
      18 (90%). Gastrointestinal signs and symptoms were also common. Peripheral blood
      eosinophilia occurred in 15 (75%). Twelve (60%) had secondary infection, and 3
      (15%) had bacterial lung abscesses. All were treated with thiabendazole, 25 mg/kg
      twice daily; on average, patients without ARDS were treated for 3 days, versus 7
      days for those with ARDS. Seventy percent responded to therapy; 30% died.
      Preexisting chronic lung disease and ARDS were statistically significant
      predictors of a poor prognosis.

PMID- 8545687
TI  - Integrated management of venous thromboembolism.
AB  - Diagnostic methods for pulmonary embolism and deep vein thrombosis of the lower
      extremity are intertwined, since the latter nearly always precedes the former.
      Recent prospective studies show that an independent clinical estimate of disease
      probability helps to refine probability estimates of ventilation-perfusion lung
      scans and of ultrasonography with compression, reducing the need for pulmonary
      angiography and contrast venography. Repeated ultrasonography with compression
      can also be used to stratify patients into groups that are at high or low risk
      for subsequent pulmonary embolic events. I give algorithms and guidelines for the
      clinical use of these findings. Effective treatment of acute venous
      thromboembolism depends on achieving an antithrombotic state with heparin and
      warfarin. I give recommendations for dosing and monitoring heparin and warfarin
      that are based on knowledge of heparin blood levels and on use of the
      international normalized ratio with warfarin therapy. Use of low-molecular-weight
      heparin to prevent deep vein thrombosis is briefly described.

PMID- 8545688
TI  - Palliative procedures for pancreatic cancer: when and which one?
AB  - Pancreatic cancer usually requires palliative rather than curative therapy.
      Palliative procedures should have low morbidity and mortality, provide a good
      quality of life, and necessitate minimal hospitalization. The surgeon,
      endoscopist, and radiologist all play a role in delivering effective palliation
      to properly selected patients.

PMID- 8545689
TI  - Drug therapy in attention-deficit hyperactivity disorder.
AB  - Of 292 patients (210 males and 82 females) receiving medication for attention
      deficit hyperactivity disorder (ADHD), 272 (93%) responded well to sustained
      release dextroamphetamine (D-Amp) and 21 patients (7%) to sustained-release
      methylphenidate (MPD). The dose of D-Amp ranged from 0.2 to 3.6 mg/kg/day and the
      dose of MPD from 1.4 to 7.7 mg/kg/day, without side effects requiring cessation
      of therapy. This suggests that the clinical improvement rate can be increased to
      nearly 100% in appropriate situations.

PMID- 8545690
TI  - Detection of clonal immunoglobulin heavy-chain gene rearrangements in cases of
      suspected lymphoproliferative disorders: comparison of polymerase chain reaction
      and Southern blot analysis.
AB  - Demonstration of clonality is supportive of a diagnosis of malignancy in cases of
      lymphoproliferative disorders. Determination of clonality at the molecular level
      is currently accomplished by Southern analysis; however, the polymerase chain
      reaction offers a potential alternative that is rapid, simple, and less
      expensive. To test its feasibility as a diagnostic test, we amplified the DNA
      from 121 suspected lymphoproliferative disorders submitted for gene rearrangement
      studies. In comparison to Southern analyses, a sensitivity of 70% and specificity
      of 96% were obtained. To test the effect of primer variability in the joining
      region of the heavy-chain gene, we substituted a more degenerate primer but found
      no changes in sensitivity or specificity. We conclude that the polymerase chain
      reaction has current application with minute or fixed specimens and may generally
      serve as a rapid, initial evaluation for B-cell clonality, followed by Southern
      analysis in negative cases. However, higher overall sensitivity must be achieved
      before this technique can replace Southern analysis as the method of choice in
      determining clonal gene rearrangements.

PMID- 8545691
TI  - Short-term volunteer staffing of a hospital.
AB  - We surveyed 136 physicians, nurses, dentists, physician assistants, and other
      medical professionals who were residents of the United States and had volunteered
      their professional services for 6 months or less from October 1992 through
      January 1994 at St. Jude Hospital, a rural hospital on the island of St. Lucia in
      the southern Caribbean. This hospital has relied almost entirely on volunteer
      staffing over the past 27 years. The survey explored motivations for
      volunteering, opinions on medical care, and personal background. Of those who
      returned the questionnaire (a 68% response rate), 98% considered overall care to
      be adequate or better than adequate despite limited hospital facilities and
      frequent changes of personnel. Seventy-seven percent cited unavailability of
      opportunities, limited backup mediated coverage in locales where they might want
      to volunteer, and concerns about licensing and insurance as reasons for not doing
      volunteer work in the United States.

PMID- 8545692
TI  - Does hemodilution exist? Effects of saline infusion on hematologic parameters in
      euvolemic subjects.
AB  - The effects of intravenous fluids on hematocrit are debated. We sought to
      determine whether maintenance or bolus fluid therapy causes a significant change
      in the hematocrit and other hematologic parameters included in the complete blood
      count. Nine subjects completed a randomized three-period crossover designed trial
      in which they were given no fluid, maintenance fluid, or a bolus of fluid
      followed by maintenance fluid. We measured complete blood counts at baseline, 1
      hour, 4 hours, and 8 hours. In the bolus fluid trial, the hemoglobin and
      hematocrit values (mean +/- SEM) decreased by a maximum of 1.5 +/- 0.1 g/dL and
      4.1 +/- 0.3% at 1 hour. There was no difference in hemoglobin or hematocrit
      during the no fluid or maintenance fluid treatments. No significant changes
      occurred in white blood cell or platelet counts. We demonstrated that maintenance
      fluid infusions do not significantly after the complete blood count. Saline bolus
      is associated with a significant decrease in hemoglobin and hematocrit, but these
      parameters trend toward baseline over time.

PMID- 8545693
TI  - Laparoscopic tubal sterilization in obese women: experience from a teaching
      institution.
AB  - To determine whether laparoscopy presents any significant risks for tubal
      sterilization in obese women, we retrospectively reviewed the records of 248
      consecutive patients who had laparoscopic tubal sterilization between January and
      December 1991 at our institution. The 147 obese women were compared with the 101
      nonobese women as controls for the study parameters. Two methods of closed
      laparoscopy were used as interval procedures, with similar proportions in obese
      and nonobese women. We observed no complications in any patient, and there were
      not significant differences in the mean operating time and estimated blood loss
      between the two groups of women. We concluded that laparoscopy should be
      considered safe and laparoscopic tubal sterilization can be performed in obese
      women with the same efficiency, morbidity rate, and length of hospitalization as
      in nonobese women.

PMID- 8545694
TI  - Laparoscopic fundoplication in the treatment of severe gastroesophageal reflux
      disease: preliminary results of a prospective trial.
AB  - To determine the technical feasibility and success of laparoscopic fundoplication
      in the treatment of severe gastroesophageal reflux disease (GERD), 18 consecutive
      adult patients were enrolled in a prospective study. All patients had received
      unsuccessful conservative treatment, were refractory to medical management, or
      had recurrence of symptoms of esophagitis after omeprazole therapy. All patients
      had severe acid reflux on 24-hour esophageal pH monitoring, endoscopic evidence
      of previous or ongoing esophagitis, and a defective lower esophageal sphincter on
      manometry. Complete (Nissen) fundoplication was done in 11 and partial (Toupet)
      fundoplication in 7 patients; the mean operative time was 183 minutes (range, 120
      to 357 minutes). Feedings were initiated on the first postoperative day, and the
      average length of stay was 2.6 days (range, 1 to 6). There were no deaths or
      conversions to laparotomy. Postoperative morbidity consisted of transient
      bloating in three patients and dysphagia requiring dilatation in four patients.
      Return to work or normal activity averaged 19 days (range, 3 to 28), and 17
      patients (94%) reported good to excellent results, with a median follow-up of 7
      months. Laparoscopic fundoplication is technically feasible and offers a sound
      surgical alternative to patients with refractory GERD, but longitudinal follow-up
      is required to confirm long-term results.

PMID- 8545695
TI  - Rhinosporidiosis: three domestic cases.
AB  - Three cases of rhinosporidiosis in Americans who had not traveled abroad are
      reported. We believe this is the largest cluster of indigenous cases reported in
      the United States. The three patients had lived in rural northeast Georgia all of
      their lives. One had a polypoid conjunctival lesion, and the two others had nasal
      polyps. In each case, the diagnosis was made by demonstrating morphologically
      distinctive fungal elements in histopathologic sections. Clinically,
      rhinosporidiosis had not been suspected.

PMID- 8545696
TI  - Organism isolation and serum bactericidal titers in oral antibiotic therapy for
      pediatric osteomyelitis.
AB  - Isolation of the etiologic organism and monitoring of serum bactericidal titers
      are considered necessary in oral antibiotic therapy for osteomyelitis. Over a 5
      year period, 26 pediatric patients with hematogenous osteomyelitis were treated
      with sequential parenteraloral therapy. No organism was isolated in 9 cases, and
      bactericidal titers were determined in only 7 cases. All patients did well,
      raising questions about the conventional prerequisites invoked for oral treatment
      of skeletal infections.

PMID- 8545697
TI  - Bayesian analysis of noninvasive versus oral temperature measurements to
      determine hypothermia in postoperative patients.
AB  - Measurement of body temperature in the postanesthesia care unit (PACU) is an
      important parameter in patient management. Failure to reach minimal acceptable
      body temperature standards has been associated with physiologic derangements, the
      application of additional therapy, and prolonged PACU stays. Newer methods to
      monitor temperature introduced into the PACU have been touted to be adequate for
      detecting clinically significant changes in temperature. In this study, skin core
      temperature-corrected liquid crystal thermography (LCT), axillary (AT)
      electronic, and infrared tympanic membrane (ITT) temperatures were compared with
      oral thermistor thermometry (OT) in 205 PACU patients. Regression analysis
      suggests that when compared with the oral method, ITT tends to overestimate and
      AT and LCT tend to underestimate oral temperatures. Mean temperatures obtained by
      LCT (35.5 +/- 1.0 degrees C), AT (35.1 +/- 0.9 degrees C), and ITT (36.3 +/- 0.8
      degrees C) differed significantly from OT (36.0 +/- 0.7 degrees C) mean
      temperatures. We applied Bayesian analysis to assess the sensitivity and
      specificity of each method, using a hypothermia reference of < 36 degrees C.
      Results suggest that the definition of hypothermia may depend on the modality
      used to assess body temperature in the PACU.

PMID- 8545698
TI  - Using the KTP/532 laser to control epistaxis in patients with hereditary
      hemorrhagic telangiectasia.
AB  - Osler-Weber-Rendu disease remains a challenging clinical management problem. We
      have found the potassium-titanyl-phosphate laser (KTP/532) for photocoagulation
      of intranasal telangiectases to be useful in controlling epistaxis refractory to
      traditional surgical therapy. We present the case of a patient who had Osler
      Weber-Rendu disease previously treated with partial septectomy, turbinectomy, and
      intranasal dermoplasty. A technique using the KTP laser for photocoagulation of
      intranasal telangiectases is described. This technique has resulted in reducing
      the frequency of epistaxis, decreasing the need for transfusions, diminishing
      hospital admissions, and improving quality of life for this patient. The KTP
      laser plays an important role in the management of recurrent epistaxis in
      patients with Osler-Weber-Rendu disease.

PMID- 8545699
TI  - Painless thyroiditis occurring during long-term treatment with interferon alfa in
      a patient with chronic active hepatitis C.
AB  - We describe here painless thyroiditis during interferon (IFN) therapy in a 65
      year-old man with chronic active hepatitis C. The patient had hypothyroidism in
      the late stage of a 24-week course of treatment with IFN-alpha. After cessation
      of the treatment a small, firm goiter was noticed, and chronic focal thyroiditis
      was diagnosed histologically. Analyses of the stock serum samples drawn before,
      during, and after IFN-alpha therapy revealed transient hyperthyroidism followed
      by transient hypothyroid states with aggravation of antithyroid hormone antibody
      titers. These findings suggest that long-term IFN-alpha therapy caused painless
      thyroiditis with aggravation of autoimmunity in our patient with preexisting
      chronic thyroiditis.

PMID- 8545701
TI  - Peritonitis due to Penicillium sp in a patient receiving continuous ambulatory
      peritoneal dialysis.
AB  - Infectious peritonitis is a common complication of continuous ambulatory
      peritoneal dialysis (CAPD). Only one case of CAPD-related peritonitis due to
      Penicillium sp has previously been reported. We present a second case in which
      fungal colonies were observed on the inner surface of the CAPD catheter. The
      infection was successfully treated with catheter removal and intravenous
      amphotericin B.

PMID- 8545702
TI  - Moyamoya disease in an adult with Down syndrome: comparison of magnetic resonance
      angiography and conventional angiography.
AB  - Moyamoya disease, or idiopathic progressive arteriopathy, is a vascular occlusive
      disease that results in stenosis of the internal carotid arteries, stimulating
      the development of collaterals and telangiectatic vasculature from basilar and
      leptomeningeal arteries. Within the past several years, several reports have
      suggested that children with Down syndrome can develop moyamoya vasculopathy. We
      present the first reported magnetic resonance angiographic diagnosis of moyamoya
      disease in an adult with Down syndrome. This was also confirmed by conventional
      cerebral angiography.

PMID- 8545700
TI  - Recurrent amiodarone pulmonary toxicity.
AB  - Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary
      toxicity, with an estimated mortality of 1% to 33%. Standard treatment for
      amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and
      steroid therapy. We report a case of APT that recurred after withdrawal of
      steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT
      is a rare clinical entity that has been reported only twice in recent literature.

PMID- 8545703
TI  - Blue roads and homework.

PMID- 8545704
TI  - Medication for attention-deficit hyperactivity disorder: balancing art and
      science.

PMID- 8545705
TI  - Chest pain and breast implants.

PMID- 8545706
TI  - Chest pain and breast implants.

PMID- 8545707
TI  - Chest pain and breast implants.

PMID- 8545708
TI  - Chest pain and breast implants.

PMID- 8545709
TI  - Clinical research 2000.

PMID- 8545710
TI  - Role of sodium in the pathophysiology of secondary spinal cord injury.
AB  - STUDY DESIGN: Experimental study using an in vitro model of compressive injury to
      isolated adult rat dorsal column axons. OBJECTIVES: To examine the role of
      extracellular Na+ (Na+e) in mediating secondary injury to spinal cord axons after
      compressive trauma. The mechanisms of intracellular sodium entry were examined
      using ion substitution techniques and pharmacologic blockers. SUMMARY OF
      BACKGROUND DATA: There is evidence that intracellular Na+ entry potentiates
      hypoxic-ischemic cell death by causing cytotoxic cell swelling, intracellular
      acidosis, and gating of Ca++ entry through reverse activation of the Na(+)-Ca++
      exchanger. In the present study, we have examined the role of Na+e in the
      pathophysiology of spinal cord injury. METHODS: Dorsal column segments isolated
      from the thoracic cord of adult rats (n = 40) were pinned in a recording chamber
      and superfused with oxygenated Ringer's solution. Extracellular field potentials
      were recorded from glass microelectrodes (150 mmol KCl; 5-10 mol). Injury was
      accomplished in vitro by compression with a modified aneurysm clip (closing
      force, 2 g) for 15 seconds. The effect of zero Na+e (equimolar substitution with
      NMDG+), the Na(+)-H+ exchange blocker amiloride, the Na+ channel blocker
      procaine, and the Na(+)-Ca++ exchanger blocker benzamil on CAP recovery after
      compressive injury were assessed. RESULTS: Pretreatment with zero Na+, amiloride
      and procaine conferred significant neuroprotection (P < 0.05). In contrast, the
      NCE blocker benzamil was ineffective in attenuation secondary injury.
      CONCLUSIONS: Reduction of extracellular Na+, inhibition of the Na(+)-H+ exchanger
      or blockade of voltage gated Na+ channels is neuroprotective after spinal cord
      injury. The mechanism of Na(+)-associated cytotocity does not involve reverse
      gating of the Na(+)-Ca++ exchanger.

PMID- 8545711
TI  - Biomechanical evaluation of cervical spine stabilization methods using a porcine
      model.
AB  - STUDY DESIGN: The biomechanical stability of three different methods of cervical
      spine stabilization was evaluated in a porcine model. Specimens were tested in
      flexion, extension, and axial rotation. OBJECTIVES: Our goal was to determine if
      posterior lateral mass plating after anterior reconstruction provided more
      stability compared with unicortical or bicortical anterior plate fixation after a
      simulated corpectomy. SUMMARY OF BACKGROUND DATA: Previous implant biomechanical
      evaluations use ligamentous and intervertebral disc disruption models under
      constrained and nonrepetitive loading. This study examines implant performance
      using a corpectomy model loaded for multiple cycles, allowing for unconstrained
      motion. METHODS: Twenty-one porcine cervical spines were destabilized with a one
      level cervical corpectomy and reconstructed with an anterior methacrylate graft.
      Each construct was stabilized with either an AO Morscher plate system with
      unicortical, self-locking screws; a Caspar plate with biocortical screws; or two
      posterior lateral mass plates. Testing with cyclic loads was performed on an MTS
      machine in flexion, extension, and axial rotation. RESULTS: There was no
      statistical difference between the two anterior forms of fixation in flexion,
      extension, or axial rotation. Posterior lateral mass plating was significantly
      more stable than either anterior construct. Screw loosening was seen more
      frequently with bicortical Caspar plating. CONCLUSIONS: After a single-level
      cervical corpectomy and idealized grafting, all three surgical constructs
      provided stability equal to or greater than the intact condition in flexion,
      extension, and axial rotation. In unstable cervical spine injury patterns
      involving anterior disruption, this study supports the use of anterior grafting
      combined with posterior lateral mass plating to achieve maximum stability.

PMID- 8545712
TI  - The effect of nicotine on incorporation of cancellous bone graft in an animal
      model.
AB  - STUDY DESIGN: A basic science study using a rabbit model of bone graft
      revascularization in the distal femoral metaphysis. OBJECTIVES: The goal of the
      present study was to determine the effect of nicotine on the revascularization
      and incorporation of autogenous iliac crest bone graft implanted in an orthotopic
      location. SUMMARY OF BACKGROUND DATA: Although nicotine is the major toxin in
      cigarettes, it has not been confirmed as the primary factor affecting bone
      metabolism, and although the effects of smoking on bone homeostasis have been
      well studied, the effect of nicotine on new bone formation and neovascularization
      in the setting of bone graft transplantation has not been well studied. METHODS:
      Twenty-four New Zealand white rabbits were randomly divided into two groups to be
      exposed to nicotine or saline control. A cancellous iliac crest bone graft was
      harvested and implanted in the lateral distal femur. Mini-osmotic pumps were used
      to deliver continuous serum levels of nicotine. The animals were killed at the
      following intervals: 1 week (n = 6), 2 weeks (n = 12), and 4 weeks (n = 6). The
      vascular tree was injected with Microfil silicone rubber solution, and the degree
      of revascularization was determined with a semiautomated image analysis system to
      determine the area of vascularization for each specimen. RESULTS: All seven of
      the control (no nicotine) animals harvested at 1 or 2 weeks had over 50% bony
      vascular ingrowth, whereas only four of the nine nicotine-exposed animals showed
      over 50% bony vascular ingrowth. These differences were statistically significant
      (P = 0.03) using the Fischer exact test. By the fourth week (after nicotine
      levels in experimental animals had diminished), the revascularization of the
      nicotine-exposed grafts was indistinguishable from that of grafts in the animals
      that were not exposed to nicotine. CONCLUSIONS: We conclude the following. 1)
      Uniform dosages of nicotine in the rabbit model decreases the vascular ingrowth
      into autogenous cancellous bone graft. 2) The inhibitory effect of nicotine
      varies between animals, suggesting predisposition in some. 3) The vascular
      effects are reversible within 2 weeks of elimination of nicotine, although late
      bony resorption continues beyond the time of high serum nicotine levels.

PMID- 8545713
TI  - Evaluation of porous biphasic calcium phosphate ceramics for anterior cervical
      interbody fusion in a caprine model.
AB  - STUDY DESIGN: This study compared the efficacy of characterized 50/50
      hydroxyapatite/beta-tricalcium phosphate ceramics of 30%, 50%, and 70% porosity
      and autograft to promote interbody spinal fusion at C2-C3 and C5-C6 in 24 goats:
      12 at 3 months and 12 at 6 months. OBJECTIVES: Radiographs, histology, dual
      energy x-ray absorptiometry analysis, and biomechanical testing were used to
      evaluate the ability of the 30%, 50%, and 70% porous 50/50 hydroxyapatite/beta
      tricalcium phosphate ceramics and autograft to promote cervical interbody fusion.
      SUMMARY OF BACKGROUND DATA: The conundrum in the use of calcium phosphates for
      interbody fusion is what porosity is most effective to promote ingrowth yet
      strong enough to resist compressive stresses found in the spine? It is known that
      the ability for bone ingrowth increases and the compressive strength decreases as
      porosity of the ceramic is increased. Dense ceramics remain intact but may be
      surrounded by fibrous tissue. Porous ceramics have good ingrowth but may
      fracture. METHODS: Radiographs were evaluated for fusion and fracture or collapse
      of the ceramics or autograft. Dual energy x-ray absorptiometry was used to
      evaluate the fusion mass. Treated motion segments underwent biomechanical testing
      to quantify the flexibility of the segment. Undecalcified and decalcified
      histologic analysis were performed to evaluate the presence or absence of a bony
      union. RESULTS: Thirty percent, 50%, and 70% porous ceramics had better
      radiographic fusion scores than the autograft at 3 and 6 months. Incidence of
      ceramic fracture did not increase with porosity and was equivalent to the
      collapse of autograft, although ceramics maintained disc height when fracture
      occurred. No statistically significant differences were found between autograft
      and the porous ceramics with biomechanical testing and peri-implant bone mineral
      density values as measured by dual energy x-ray absorptiometry. At 3 months,
      histologic analysis showed a union rate of 0% for autograft and 30% porous
      ceramic, 67% for 50% porous ceramic, and 83% for 70% porous ceramic. At 6 months,
      the union rate was 67% for the 30%, 50%, and 70% porous ceramics and 50% for
      autograft. CONCLUSIONS: Thirty percent, 50%, and 70% porous ceramics performed
      equal to or better than autogenous bone after 3 and 6 months. There may be
      promise for the use of 50/50 hydroxyapatite/beta-tricalcium phosphate in spine
      surgery as the need to harvest autograft from the iliac crest is obviated, and
      complications and cost associated with the harvest are avoided.

PMID- 8545714
TI  - Comparison between allograft plus demineralized bone matrix versus autograft in
      anterior cervical fusion. A prospective multicenter study.
AB  - STUDY DESIGN: This study analyzed the fusion results of an allograft
      demineralized bone matrix composite versus autograft in a prospective series of
      patients undergoing surgery for cervical disc disease. OBJECTIVES: To determine
      the fusion rates of allograft-demineralized bone matrix composite in anterior
      cervical fusion as compared with the gold standard autograft. SUMMARY OF
      BACKGROUND DATA: For the anterior cervical fusion, the use of freeze-dried
      allograft is well documented in the literature, citing its effectiveness and
      inferior fusion rates. The use of demineralized bone matrix in conjunction with
      freeze-dried allograft in anterior cervical fusion has not been reported.
      METHODS: This study was done in a prospective fashion in two medical centers. One
      group received autograft from the anterior iliac crest, whereas others received
      freeze-dried allograft augmented with demineralized bone matrix (Grafton,
      Osteotech, Inc., Shrewsbury, New Jersey). For the autograft group, the standard
      Smith-Robinson grafting technique was used. For the allograft composite group,
      demineralized bone matrix was pasted onto the freeze-dried allograft and into the
      disc space before graft insertion. The autograft group consisted of 38 patients
      with age ranging 26-71 years (mean, 46.1 years) and follow-up periods of 12-33
      months (mean, 18.4 months). There were 19 one-level, 17 two-level, and two three
      level fusions. Similarly, the allograft group consisted of 39 patients with age
      ranging 28-80 years (mean, 48.0 years) with follow-up period of 12-31 months
      (mean, 17.5 months). There were 19 one-level, 16 two-level, and four three-level
      fusions. Clinical and radiographic follow-up evaluations were completed at 3
      month intervals. Radiographs taken 12 months after surgery were analyzed blindly.
      RESULTS: Pseudarthrosis developed in 46.2% of patients (33.3% of levels) in the
      allograft-demineralized bone matrix group compared with 26.3% (22% of levels) in
      the autograft group (P = 0.11 for patients, P = 0.23 for levels). For patients
      undergoing two-level fusions, 37.5% of allograft-demineralized bone matrix failed
      compared with 23.5% of autografts. For single-level fusions, 47.4% of allograft
      patients developed a pseudarthrosis compared with 26.3% in the autograft group.
      Graft collapse of > or = 3 mm was noted in 11% of the autograft group versus 19%
      in the allograft-demineralized bone matrix group (P = 0.32). Graft collapse of >
      or = 2 mm occurred in 24.4% of autograft patients compared with 39.7% of the
      allograft-demineralized bone matrix group (P = 0.09). Smokers had an increased
      rate of pseudarthrosis (47.1%) compared with nonsmokers (27.9%, P = 0.13).
      CONCLUSIONS: The study revealed that the allograft-demineralized bone matrix
      construct gives a higher rate of graft collapse and pseudarthrosis when compared
      with autograft in a prospective series, although the differences were not
      statistically significant. The pseudarthrosis rate in the series may be high
      because of the large percentage of smokers and radiographic evaluation
      techniques. For the purpose of solid radiographic fusion, the use of autograft is
      recommended in anterior cervical surgery until other acceptable osteoinductive
      materials are developed.

PMID- 8545715
TI  - The use of autologous skull bone grafts for posterior fusion of the upper
      cervical spine in children.
AB  - STUDY DESIGN: Traditionally bone grafts used in posterior cervical fusion have
      been harvested from the iliac crest, rib, tibia, or fibula. Their use is not
      without significant morbidity, and it is often difficult to harvest suitable
      quantities of good quality bone in children. We have used autologous calvarial
      bone secured by sublaminar wires in seven patients with congenital spinal
      anomalies to achieve craniocervical stabilization and fusion. OBJECTIVES: To
      detail our experiences with this new method of harvesting autologous bone grafts
      from the patient's skull for occipitocervical fusion in a pediatric practice.
      SUMMARY OF BACKGROUND DATA: Calvarial bone has been used extensively in
      craniofacial reconstructive work with good long-term results and with no
      significant bone resorption. The use of membranous bone is supported by several
      basic science studies reported in the plastic surgery literature that claim a
      superiority over endochondral bone regarding fusion. In the present study,
      autologous calvarial bone has been used in the treatment of seven cases of
      congenital upper cervical spine instability associated with neurologic deficit.
      This method circumvents many of the problems attached to the use of traditional
      donor sites and provides good quality bone in large quantity that can be
      specifically tailored to match the contours of the craniocervical junction.
      METHOD: We used autologous calvarial bone secured by sublaminar wires in seven
      children with congenital spinal anomalies to achieve craniocervical stabilization
      and fusion. The ensuing calvarial defect was repaired using split-thickness
      parietal bone with the bone graft, which was ultimately used for the cervical
      fusion and acted as a template to obtain a mirror image and exact match to
      achieve good cosmetic results. The patients were immobilized after surgery in a
      halo orthosis for 3 months. RESULTS: Satisfactory results (100% fusion) were
      achieved in all seven cases with no attendant morbidity related to the method of
      graft procurement. CONCLUSIONS: We recommend this technique as a safe and
      effective alternative to the more traditional means of graft procurement
      previously used in cases of craniocervical instability in children.

PMID- 8545716
TI  - Radiographic appearance of the odontoid lateral mass interspace in the
      occipitoatlantoaxial complex.
AB  - STUDY DESIGN: This is an anatomic study in which the odontoid lateral mass
      interspace is evaluated radiographically in various positions of upper cervical
      spine rotation. OBJECTIVES: The objectives are to determine whether odontoid
      lateral mass interspace asymmetry exists in the ligamentously intact cervical
      spine and to define odontoid lateral mass interspace behavior during atlantoaxial
      rotation. SUMMARY OF BACKGROUND DATA: Controversy exists regarding the behavior
      of the odontoid lateral mass interspace during atlantoaxial rotation. The meaning
      of interspace asymmetry varies depending on the author and the method of study.
      Atlas fractures account for 7% of cervical spine fractures and are frequently
      associated with other cervical fractures, so an understanding of the radiographic
      anatomy is crucial to the evaluation of these patients. METHODS: Ten human
      cadaveric cervical spines were dissected of all but ligamentous soft tissue and
      were mounted and prepared for radiographic study in neutral position and in
      varying degrees of right and left rotation. Radiographs were evaluated for
      odontoid lateral mass interspace asymmetry in neutral and in rotated positions,
      and data were analyzed. RESULTS: Measurable asymmetry could be shown when
      comparing neutral positions and when comparing rotated with neutral positions. A
      statistically significant difference could not be proven in this asymmetry,
      although clinical significance is suggested by the analysis of the data.
      CONCLUSION: Measurable asymmetry can be present in the neutrally positioned,
      ligamentously intact atlanto-axial complex and is not necessarily indicative of
      instability. This agrees with the concept of the "neutral zone" as described by
      White and Panjabi in Clinical Biomechanics of the Spine. There is a trend for
      increasing odontoid lateral mass interspace on the side to which the head is
      rotated, and this odontoid lateral mass interspace is measurably different from
      the contralateral odontoid lateral mass interspace, indicating that odontoid
      lateral mass interspace asymmetry is not a good indicator for cervical
      instability in the otherwise asymptomatic individual.

PMID- 8545717
TI  - Intramedullary changes of the spinal cord in cervical spondylotic myelopathy.
AB  - STUDY DESIGN: This study retrospectively reviewed magnetic resonance imaging and
      delayed computed tomography after myelography of cervical spondylotic myelopathy
      patients who needed surgical treatment. OBJECTIVES: The purpose of this study is
      to clarify the meaning of high magnetic resonance intensity areas in cervical
      spondylotic myelopathy patients. SUMMARY OF BACKGROUND DATA: There is no
      conclusion whether the high magnetic resonance signal intensity areas can be a
      predictor for surgical results or not. METHODS: Thirty-one patients with cervical
      spondylotic myelopathy were examined with magnetic resonance imaging before
      surgery and delayed computed tomography after surgery. The presence or absence of
      high intensity areas in the spinal cord was compared with clinical symptoms and
      surgical outcomes. RESULTS: Twenty-three (74%) of 31 patients showed high
      intensity areas in the spinal cord on the T2-weighted image. Among these 23
      patients, 18 revealed bilateral intramedullary "snake eyes" enhancement in
      delayed computed tomography. The presence of high intensity areas did not
      correlate with the surgical outcomes. Patients with multisegmental (linear) high
      intensity areas frequently manifested muscle atrophy in upper extremities.
      CONCLUSIONS: High intensity areas on T2-weighted magnetic resonance imaging were
      not correlated with the severity of myelopathy or surgical outcomes evaluated by
      the Japanese Orthopaedic Association score. Magnetic resonance imaging or delayed
      computed tomography in this study could not rule out the presence of white matter
      changes, including axonal loss or demyelination. Multisegmental (linear) high
      intensity areas on T2-weighted magnetic resonance imaging were associated with
      clinical evidence of extensive anterior horn cell and radiographic evidence of
      gray matter cavitation.

PMID- 8545718
TI  - Magnetic-evoked compound muscle action potential neuromonitoring in spine
      surgery.
AB  - STUDY DESIGN: Muscle action potentials elicited by paired transcranial magnetic
      stimulation were recorded during spine surgery in 34 patients. Anesthesia was
      based on ketamine and fentanyl. OBJECTIVES: To evaluate the optimal anesthetic
      regimen to be used for transcranial magnetic stimulation, and to determine the
      clinical import of magnetic-evoked compound muscle action potentials. SUMMARY OF
      BACKGROUND DATA: Muscle action potential by transcranial magnetic stimulation has
      been difficult to record under general anesthesia. Ketamine is known to not
      suppress the muscle responses, although no conclusive clinical study has been
      reported. METHODS: Paired transcranial magnetic stimulation was delivered as
      muscle action potentials were recorded from the limb musculature. RESULTS:
      Neuromonitoring was reliable in 56% of total cases and in 82% of the recent cases
      after reducing fentanyl dosage. Paired magnetic stimulation was an excellent
      facilitation technique for reliable monitoring. At higher dosages, fentanyl and
      ketamine decreased the reproducibility of the responses. CONCLUSIONS: Magnetic
      evoked compound muscle action potential neuromonitoring is a sensitive and
      selective motor pathway monitoring method that covers the entire motor pathway,
      including the white and gray matter of the spinal cord. Ketamine-based anesthesia
      is a good choice for this purpose.

PMID- 8545719
TI  - A new method of multisegment motor pathway monitoring using muscle potentials
      after train spinal stimulation.
AB  - STUDY DESIGN: Evoked muscle and nerve action potentials after spinal stimulation
      for intraoperative monitoring were investigated using a modified stimulation
      technique. Animal experiments and clinical application were performed.
      OBJECTIVES: To contrive a useful method of intraoperative motor pathway
      monitoring under inhalation anesthesia. SUMMARY OF BACKGROUND DATA: Many
      different kinds of procedures have been reported. No reliable method that
      reflects pure motor tract function has been established. METHODS: Characteristic
      of our stimulating technique was the use of numbered consecutive pulses ("train
      stimulation"). In 16 cats, optimum condition of train stimulation, effects of
      anesthetic agents, and conductive pathway were examined. In 35 patients, muscle
      potentials evoked by train stimulation were recorded, and clinical usefulness was
      evaluated. RESULTS: In the experimental study, the optimum stimulus condition was
      determined 1 ms interstimulous interval train of five pulses. Conductive pathway
      of this method was identified as a lateral column by selective spinal cord
      transection. In the clinical application, by using train stimulation,
      multisegmental muscle potentials were obtainable even using inhalation
      anesthetics. CONCLUSIONS: The facilitative effects of train stimulation,
      attributed to temporal summation, are considered to overcome the suppression of
      inhalation anesthesia. The evoked muscle potentials by train spinal stimulation
      reflect the functions of pure motor tract and is the only, extremely efficient
      method for intraoperative motor pathway monitoring.

PMID- 8545720
TI  - Long-term follow-up evaluation of surgery for ossification of the posterior
      longitudinal ligament.
AB  - STUDY DESIGN: We compared anterior and posterior surgery for cervical myelopathy
      resulting from ossification of the posterior longitudinal ligament. Surgical
      techniques, based on shape and distribution of ossification of the posterior
      longitudinal ligament, were divided into four technical phases. OBJECTIVES: Long
      term follow-up data on anterior and posterior surgery were analyzed to establish
      guidelines for surgical treatment. SUMMARY OF BACKGROUND DATA: Comparison of
      anterior and posterior surgery is difficult because surgical techniques,
      ossification of the posterior longitudinal ligament shape classifications, and
      surgical criteria varied. No reports have accurately assessed spinal changes over
      a 10-year follow-up period. METHODS: Fifty patients received anterior surgery and
      65 received posterior surgery between 1968 and 1993. Assessment after surgery was
      based on the recovery rate using the scoring system of the Japanese Orthopaedic
      Association. Spinal changes in the anterior group were assessed radiographically.
      RESULTS: Recovery and final results improved with phase after anterior, but not
      posterior, surgery. Neurologic deterioration after initial recovery was lower for
      the anterior group. One third of patients in the anterior group followed for more
      than 7 years exhibited neurologic deterioration, with most showing these changes
      within 10 years. Worsening was attributed to insufficient removal of lateral,
      superior, or inferior ossification of the posterior longitudinal ligament,
      reossification at the excision site, kyphotic malalignment, growth of
      ossification at upper cervical levels, or untreated complicated hypertrophy of
      the posterior longitudinal ligament. Many patients showed a good outcome after
      surgery. Accurate alignment and long-range fusion improved results. If the cord
      was compressed in a canal narrowed to under 3 mm, anterior surgery was considered
      "too risky." CONCLUSIONS: Complete extirpation of ossification of the posterior
      longitudinal ligament as confirmed by ultrasonography during surgery and long
      range fusion with fibular grafts is advocated in the management of ossification
      of the posterior longitudinal ligament.

PMID- 8545721
TI  - Glenoid cysts mimicking cervical radiculopathy.
AB  - STUDY DESIGN: Patients are often referred for the evaluation of neck or radiating
      shoulder or arm pain who are suspected of having a possible cervical spine origin
      of their symptoms. Careful evaluation may show ganglion cysts of the glenohumeral
      joint mimicking symptoms of cervical radiculopathy. OBJECTIVES: To present a
      series of patients in whom cysts originating from the glenohumeral joint caused
      symptoms mimicking cervical radiculopathy. SUMMARY OF BACKGROUND DATA:
      Suprascapular nerve entrapment in the suprascapular notch by ganglion cysts from
      the glenohumeral joint has been described as the source of vague radicular
      symptoms. This paper presents a series of patients referred to a spine practice
      for the evaluation of cervical radiculopathy who actually had glenoid cysts
      mimicking cervical radiculopathy. METHODS: Three hundred forty-two patients were
      evaluated for cervical radiculopathy; of these, eight had glenoid cysts that were
      the source of the patients' symptoms. RESULTS: All eight patients had a positive
      shoulder impingement sign, or, in all, symptoms were temporarily relieved with
      intra-articular lidocaine injection. Four of the eight patients had abnormal
      electromyelography and nerve conduction velocity for suprascapular nerve
      compression. Magnetic resonance imaging of the shoulder was diagnostic in all
      eight patients. CONCLUSION: Proper evaluation of the shoulder must be done
      because it may mimic symptoms of cervical radiculopathy.

PMID- 8545723
TI  - Brachytherapy for oesophageal cancer.

PMID- 8545722
TI  - Potential effectiveness of novel bone graft substitute materials.

PMID- 8545724
TI  - Penman Lecture. From Langenbuch to laparoscopes--the growth of a specialty.

PMID- 8545725
TI  - Penetrating stab wounds of the chest--when should chest physiotherapy commence? A
      comparative study.
AB  - In an effort to optimise the physiotherapy management of patients with
      penetrating stab wounds to the chest, 26 male patients, aged between 18 and 30
      years, were randomised to one of two groups on admission to Hillbrow Hospital.
      The patients in group I received chest physiotherapy immediately after insertion
      of the intercostal drain, while patients in group II received chest physiotherapy
      9-12 hours after insertion of the drain as is currently the normal hospital
      procedure. Mean duration of intercostal drainage in group I was 40 hours and that
      in group II 65.92 hours. Patients in group I had significantly shorter
      intercostal drainage times than patients in group II (P = 0.0001). Patients in
      group I had a mean hospital stay of 43.96 hours while patients in group II had a
      mean hospital stay of 77.53 hours (P = 0.0001). There was a significant
      difference in the duration of hospitalisation between the two groups, this being
      shorter in group I than in group II. The prevalence of spiking temperatures was
      also significantly lower in group I than in group II, since only 2 patients in
      group I but 8 patients in group II developed a spiking temperature (P = 0.0207).
      This study suggests that an aggressive approach of immediate chest physiotherapy
      in these patients has definite beneficial results.

PMID- 8545726
TI  - Initial experience with telebrachytherapy treatment in palliation of advanced
      oesophageal cancer.
AB  - Ten patients with advanced metastatic squamous cell carcinoma of the middle third
      of the oesophagus were treated with palliative external radiotherapy and
      intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and
      narrow lumens that did not allow the passage of a guidewire for dilatation.
      Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients. This
      finding was correlated with an increase in the size of the oesophageal lumen at
      the end of 6 weeks following treatment by barium swallow. No complications of
      treatment were noted in any patient. Low doses of external beam radiotherapy and
      high-dose-rate intraluminal brachytherapy can provide quick and effective
      palliation in advanced metastatic oesophageal carcinoma.

PMID- 8545727
TI  - Sclerosing encapsulating peritonitis--a review.
AB  - Sclerosing encapsulating peritonitis (SEP) is a syndrome of multiple causes
      which, perhaps via a common pathway, affects the small bowel in particular. When
      persistent intestinal obstruction develops, laparotomy and careful disobstruction
      of the bowel are indicated. Generally, the prognosis of SEP depends on its cause
      and the premorbid condition of the individual patient.

PMID- 8545728
TI  - Acute pseudo-obstruction of the colon (Ogilvie's syndrome) following caesarean
      section under epidural anaesthesia.
AB  - Acute pseudo-obstruction of the colon usually occurs in association with a
      systemic illness, e.g. myocardial infarction, pneumonia, sepsis, or complicates a
      major operation or trauma. The aetiology is unclear and appears to be
      multifactorial. Hypotheses have included both surgery-related dysfunction of the
      sacral parasympathetic nerves, and an imbalance of the inhibitory sympathetic and
      excitatory parasympathetic colonic innervations. We report a case of this
      condition and discuss the clinical approach to its treatment.

PMID- 8545729
TI  - Interposition of 'wide' cycloperistaltic segments into isolated segments of
      jejunum--influence on fluid perfusion.
AB  - Two isolated jejunal segments (Thiry-Vella (T-V) loops) were created in 7 dogs.
      One contained a 'wide' cycloperistaltic (C-P) segment while the other, acting as
      a control, did not. The C-P segment had the same diameter as the jejunum. Fluid
      perfusion experiments showed that there were no changes in the volume of output,
      absorption and pooling of the fluid in the T-V loops containing the 'wide' C-P
      segment. This was in contrast with significant changes shown in earlier
      experiments using 'narrow' C-P segments.

PMID- 8545730
TI  - Regeneration after in situ flushing of partially hepatectomised rat livers.
AB  - The effect of various components of the transplant procedure upon the
      regenerative process in reduced liver grafts is not known. In this study,
      partially hepatectomised rat liver remnants were flushed with 5 ml of either
      Ringer's lactate, Euro Collins solution or University of Wisconsin solution at 4
      degrees C and then 5 ml Ringer's lactate at 4 degrees C. After partial
      hepatectomy alone, the peak increase in thymidine kinase was measured at 24 hours
      (36,021 +/- 8,060 disintegrations per minute per milligram protein; the mitotic
      index was 25 +/- 7). In all the groups in which the remnant was flushed, peak
      thymidine kinase and mitotic index were measured at 48 hours. The pattern of
      ornithine decarboxylase activity was disorganised in all groups. Flushing of the
      liver remnant therefore delays the regenerative response by 24 hours. In large
      animals, including humans, regeneration appears to commence within the first 5
      days after resection. A comparable delay doubling this time might coincide with
      the onset of rejection and further compromise liver function.

PMID- 8545731
TI  - Nutritional support in the management of external pancreatic fistulas.
AB  - A prospective analysis of 20 patients with external pancreatic fistulas was
      undertaken over a 5-year period to evaluate the response of pancreatic fistulas
      to non-operative management. In 90% of patients fistula followed external trauma
      to the pancreas. There were 18 males and 2 females and the average age was 30.3
      years. Fifteen patients were given enteral nutrition alone and 5 received total
      parenteral nutrition; 2 of these received somatostatin as well. All the fistulas
      healed spontaneously within 7-80 days, with no deaths. We conclude that if the
      patient's condition is stable external pancreatic fistulas can be managed safely
      and effectively by non-operative means. Nutritional support, especially via the
      enteral route if possible, is beneficial.

PMID- 8545732
TI  - Molecular and cellular pathology of atheroma.

PMID- 8545733
TI  - Forensic medicine in deep fix.

PMID- 8545734
TI  - Towards a national paraffin safety action plan.

PMID- 8545735
TI  - Smoking in SA.

PMID- 8545737
TI  - Health care reform in South Africa--insights from the American experience.

PMID- 8545736
TI  - Registrars' concern over future of academic medicine.

PMID- 8545739
TI  - From research to service provision: the Mamre Community Health Project--7 years
      later.

PMID- 8545738
TI  - The role of human papillomavirus in cervical cancer.

PMID- 8545740
TI  - Position paper on dermatology.

PMID- 8545741
TI  - Acceptability to general practitioners of national health insurance and
      capitation as a reimbursement mechanism.
AB  - OBJECTIVE: To determine general practitioners' attitudes to national health
      insurance (NHI) and to capitation as a mechanism of reimbursement. To explore
      determinants of these attitudes. DESIGN: Cross-sectional survey by means of
      telephone interviews; four focus group discussions. SETTING: Cape Peninsula.
      PARTICIPANTS: 174 GPs randomly sampled from a total population of 874. MAIN
      OUTCOME MEASURES: Acceptance of NHI, acceptance of capitation. MAIN RESULTS:
      63.3% approved of NHI. More than 81% approved of NHI if GPs would be able to
      maintain their independent status, e.g. own premises and working hours; 82.3%
      said NHI would be a more equitable system of health care, 88% approved of the
      fact that NHI would make care by GPs more accessible, and 73% said they would
      have the capacity to treat more patients. However, 61.3% of GPs disapproved of
      capitation as a form of reimbursement. CONCLUSIONS: Most GPs in the Cape
      Peninsula were amenable to some form of NHI. However, the proportion of GPs who
      approved the introduction of NHI varied depending on details of the NHI system
      such as payment mechanisms, workload, income and effects on professional
      autonomy. A national survey of medical practitioners is recommended. The
      implications of GPs' preferences concerning the reimbursement mechanism for the
      feasibility of implementing a NHI system in South Africa require serious
      consideration by policy-makers.

PMID- 8545742
TI  - Norethisterone enantate in the treatment of premenstrual syndrome.
AB  - The aim of this prospective study was to assess whether norethisterone enantate
      can be recommended for use in patients with premenstrual syndrome (PMS) who also
      require effective contraception. The subjects were 20 patients with severe PMS
      who required effective contraception. Premenstrual symptom scores on
      norethisterone enantate and oral contraceptives were compared. Significantly
      fewer and less severe symptoms were experienced by patients on norethisterone
      enantate than those on oral contraceptives. Norethisterone enantate can therefore
      be recommended for use in patients with PMS who also require effective
      contraception.

PMID- 8545743
TI  - Morphological characterisation of the cell-growth inhibitory activity of rooperol
      and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy.
AB  - Hypoxoside is the major diglucoside isolated from the corms of the plant family
      Hypoxidaceae. It contains an unusual E-pent-1-en-4-yne 5-carbon bridging unit
      with two distal catechol groups to which the glucose moieties are attached. It is
      non-toxic for BL6 mouse melanoma cells in tissue culture on condition that the
      fetal calf serum in the medium is heat-inactivated for 1 hour at 56 degrees C in
      order to destroy endogenous beta-glucosidase activity. The latter catalyses
      hypoxoside conversion to its cytotoxic aglucone, rooperol, which, when tested as
      a pure chemical, caused 50% inhibition of BL6 melanoma cell growth at 10
      micrograms/ml. Light and electron microscopy revealed that the cytotoxic effect
      of rooperol manifested as vacuolisation of the cytoplasm and formation of pores
      in the plasma membrane. Indications of apoptosis were also found. Pharmacokinetic
      studies on mice dosed intragastrically with hypoxoside showed that it was
      deconjugated by bacterial beta-glucosidase to form rooperol in the colon.
      Surprisingly, no hypoxoside or rooperol was detectable in the serum. Only phase
      II biotransformation products (sulphates and glucuronides) were present in the
      portal blood and bile. In contrast, however, in human serum after oral ingestion
      of hypoxoside, the metabolites can reach relatively high concentrations. Rooperol
      metabolites isolated from human urine were non-toxic for BL6 melanoma cells in
      culture up to a concentration of 200 micrograms/ml. In the presence of beta
      glucuronidase, which released rooperol from the metabolites, 50% growth
      inhibition was achieved at a 75 micrograms/ml metabolite concentration. The
      supernatant of a human melanoma homogenate could also cause deconjugation of the
      metabolites to form rooperol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545744
TI  - The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung
      cancer in a phase I trial.
AB  - OBJECTIVE: To study the pharmacokinetic behaviour of hypoxoside taken orally by
      24 patients with lung cancer. DESIGN: Randomised open study with three single
      doses of 1,600, 2,400 and 3,200 mg standardised Hypoxis plant extract (200 mg
      capsules) and a multiple-dose study on the first 6 patients taking 4 capsules 3
      times daily for 11 days. PARTICIPANTS AND SETTING: Patients with histologically
      proven squamous, large-cell or adenocarcinoma were hospitalised at the Radiation
      Oncology Ward, Karl Bremer Hospital, Bellville, W. Cape. METHODS: Blood was drawn
      at regular intervals up to 75 hours after single doses and the concentrations of
      metabolites of the aglucone of hypoxoside, rooperol, were measured with a high
      performance liquid chromatography method. For the multiple-dose study blood was
      drawn before the first dose each day. Concentration-time relationships were
      analysed according to a conventional single open-compartment model and also by
      using the NONMEM digital computer programme. RESULTS: Neither hypoxoside nor
      rooperol appear in circulation. This is due to complete phase II
      biotransformation to diglucuronide, disulphate and mixed glucuronide-sulphate
      metabolites, of which the latter is the major component. Considerable
      interpatient variation in concentration-time relationships was found in the
      single-dose studies. It was due to an active enterohepatic recirculation in some
      patients and a distinct lag phase in others together with zero-order rate of
      formation of rooperol in the colon. Computer modelling indicated a single open
      compartment model in which the mass of the patient did not influence volume of
      distribution and clearance because formation of the metabolites is dependent on
      the metabolising capacity of the patient. However, the elimination of the
      metabolites follows first-order kinetics with half-lives ranging from 50 hours
      for the major metabolite to 20 hours for the two minor metabolites. Multiple-dose
      studies also showed large interpatient variation. CONCLUSION: In order to reach
      metabolite levels near 100 micrograms/ml, which have been shown to be
      tumouricidal after enzymatic deconjugation to rooperol, maintenance doses need to
      be individualised for each patient. For most patients, however, a daily dose of
      2,400 mg was sufficient.

PMID- 8545745
TI  - A phase I trial of hypoxoside as an oral prodrug for cancer therapy--absence of
      toxicity.
AB  - OBJECTIVE: To assess the toxicity of hypoxoside taken orally by 24 patients with
      lung cancer. DESIGN: Open study with patients taking 1,200-3,200 mg standardised
      Hypoxis plant extract (200 mg capsules) per day divided in 3 doses in order to
      maintain metabolite blood levels near 100 micrograms/ml. PARTICIPANTS AND
      SETTING: Patients with histologically proven squamous, large-cell or
      adenocarcinoma were hospitalised initially at the radiation oncology ward, Karl
      Bremer Hospital, Bellville, W. Cape. Thereafter they returned every 2 weeks for
      full clinical examinations. METHODS: Routine biochemical and haematological
      measurements were done. Patients underwent regular full clinical examinations
      including radiographs and computed tomography scanning according to the
      discretion of the principal investigator. RESULTS: Nineteen patients on
      hypoxoside therapy survived for an average of 4 months with progression of their
      primary tumours and metastases, while 5 survived for more than a year. One of
      them survived for 5 years and histological examination of the primary lesion
      showed absence of cancer. No toxic effects, in clinical examinations or
      biochemical or haematological measurements, were found that could be ascribed to
      the ingestion of hypoxoside. Only one occasion of possible drug intolerance, with
      anxiety, nausea, vomiting and diarrhoea, was noted. CONCLUSION: The absence of
      toxicity warrants further investigation of hypoxoside as an oral prodrug,
      especially in patients with slow-growing necrotising tumours that are inoperable
      and have high concentrations of beta-glucuronidase and sulphatase as well as a
      high sensitivity for rooperol.

PMID- 8545746
TI  - Targeted chemotherapy for parasite infestations in rural black preschool
      children.
AB  - OBJECTIVE: To investigate whether targeted chemotherapy can reduce parasite
      prevalence rates in rural black preschool children. DESIGN: The study consisted
      of a before/after trial. Stool and urine samples were analysed on four occasions
      over a 21-week period. SETTING: Creches in two rural areas of southern
      KwaZulu/Natal (coastal and inland). PATIENTS: Two hundred children of 4-6 years
      of age attending 19 creches in the area. INTERVENTION: Targeted chemotherapy
      using albendazole for nematode infestations, praziquantel for trematode and
      cestode infestations and metronidazole for protozoal infections was administered
      twice at an interval of 14 weeks. MAIN OUTCOME MEASURE: Prevalence rates.
      RESULTS: The prevalence of Ascaris lumbricoides, Trichuris trichiura and Necator
      americanus infestation decreased significantly after treatment. Reinfestation
      rates 12 weeks after treatment were 16% for A. lumbricoides, 33% for T.
      trichiura, 24% for Giardia lamblia and 3% for N. americanus. No reinfestation was
      noted for Schistosoma haematobium, Hymenolepsis or Taenia species. CONCLUSION:
      The study suggests that parasite prevalence rates in children can be reduced by
      the administration of appropriate chemotherapy at regular intervals. However, the
      provision of clean water and adequate sewerage facilities remains a high priority
      for black communities living in rural areas of South Africa.

PMID- 8545747
TI  - Follow-up of conservatively treated sleep apnoea patients.
AB  - Polysomnograms have been recorded at our laboratory since 1985 for the diagnosis
      of sleep apnoea. Until the recent availability of continuous positive airway
      pressure devices in Johannesburg, it appeared that some of our subjects were
      receiving only conservative or no treatment. Structured interviews were conducted
      with 63 patients with positive polysomnographic findings of sleep
      apnoea/hypopnoea (SAH), and, where possible, with sleeping partners. Information
      was obtained about the patients' understanding of the diagnosis by the referring
      doctor, the recommended treatment and psychosocial consequences. The primary
      reason for the initial consultation was excessive daytime sleepiness (43%).
      Diagnoses following polysomnography included SAH (65%) and narcolepsy (6%), while
      10% were told they had nothing to be concerned about. Some form of treatment was
      recommended to 80% of patients, usually weight loss (60%) or medication (59%).
      Psychosocial consequences were prominent and included a perception of reduced
      work capacity (62%) and compromised safety (56%). At the time of the interview
      90% of patients were experiencing one or more symptoms associated with SAH. These
      findings support the serious nature of SAH and confirm the need for adequate
      treatment centres in South Africa.

PMID- 8545748
TI  - Evaluation of the World Health Organisation antibody-testing strategy for the
      individual patient diagnosis of HIV infection (strategy III).
AB  - OBJECTIVE: To evaluate the World Health Organisation (WHO) antibody testing
      strategy for the individual patient diagnosis of HIV infection (strategy III).
      DESIGN: Evaluation of a combination of enzyme-linked immunosorbent assays
      (ELISAs) for the detection of antibodies to HIV-1 and HIV-2 infection. The WHO
      strategy III calls for a combination of three ELISAs, based on different antigens
      and/or differing test principles, to be used in a sequential fashion. The first
      part of the study evaluated various kits as part of a selection process. The
      second part of the study was an assessment of the three-ELISA testing strategy on
      routine sera submitted to the National Institute for Virology (NIV) for HIV
      testing. In all instances, the conventional testing protocol, which utilises a
      screening ELISA followed by a confirmatory Western blot (WB) on positive
      specimens, was used as the 'gold standard'. SETTING: The HIV-testing laboratory
      at the NIV, Johannesburg. RESULTS: In the first part of the study, all of the
      ELISA kits evaluated showed high sensitivity and specificity, and a selection of
      the kits for part two of the study was made in accordance with the WHO
      recommendation. The kits selected, in order of use, were the Biotest anti-HIV 1/2
      (test 1), Pasteur Genelavia Mixt HIV-1/2 (test 2) and Murex Wellcozyme HIV-1
      competitive assay (test 3). This combination was evaluated using 7,812 sera
      submitted to the NIV for serology testing. The sensitivities of the tests were
      highly satisfactory (99.6-100%) as were the specificities (99.2-100%). The
      positive predictive value of strategy III at various seroprevalence (0.5-25.5%)
      was > or = 99.6%. The rate of WB usage when compared with the previous HIV
      testing protocol was low (4.6%). CONCLUSIONS: The results of this study suggest
      that this testing protocol could be introduced in South Africa with considerable
      cost-saving and no reduction in specificity.

PMID- 8545749
TI  - An assessment of the statistical procedures used in original papers published in
      the SAMJ during 1992.
AB  - OBJECTIVE: To assess the statistical procedures used in original papers published
      in the SAMJ. DESIGN: Descriptive study based on a random sample of 100 papers
      from the 153 papers with methodological content that were published in the SAMJ
      during 1992. RESULTS: This review showed that 34% (95% CI (25%; 43%)) of papers
      used no statistical procedure at all or used simple descriptive statistics only.
      In sampling methods, there was a predominance of the use of the period sampling
      method as opposed to probability sampling methods. Inappropriate statistical
      methods were used in 15% (6%; 24%) of papers, while in 16% (9%; 23%) statistical
      procedures and in 13% (6%; 20%) the sampling methods used could not be
      identified. Inaccurate graphical methods were used in 17% (6%; 28%) of papers.
      Confidence intervals and power calculations are used far too infrequently, in 33%
      (19%; 47%) and 11% (3%; 19%) of appropriate papers respectively. If the Journal's
      readers are at least familiar with simple descriptive statistics, contingency
      table analysis, simple epidemiological statistics, t-test procedure and
      confidence interval calculation and interpretation, they will have a complete
      understanding of the statistical content of 60% of original articles published in
      the Journal. CONCLUSION: Guidelines for the statistical treatment of reported
      data and the statistical review of articles before publication will assist
      substantially in improving the quality of statistical analysis. More intensive
      use of available biostatistical and epidemiological expertise at the study design
      and analysis stages is needed to shift the emphasis from descriptive research to
      analytical investigation.

PMID- 8545750
TI  - Loperamide for treatment of acute diarrhoea in infants and young children. A
      double-blind placebo-controlled trial.
AB  - High-dose loperamide reduces stool output and shortens the duration of diarrhoea
      in infants receiving intravenous fluids for rehydration, but may cause
      potentially harmful side-effects in a small number of patients. This double-blind
      placebo-controlled study was undertaken to assess whether loperamide would
      shorten the hospital stay of dehydrated children in a rehydration unit. Ninety
      one patients with acute dehydrating diarrhoea received loperamide and 94 received
      placebo. The groups were clinically indistinguishable on admission to hospital.
      There was no difference between groups for the duration of rehydration or the
      number of treatment failures. The use of loperamide is not recommended in the
      treatment of infants and young children with acute diarrhoea.

PMID- 8545751
TI  - Monitoring of rotavirus infection in a paediatric hospital by RNA
      electrophoresis.
AB  - During the spring of 1987 and the autumn of 1988, stool specimens were collected
      from infants and young children in the paediatric unit at H. F. Verwoerd
      Hospital, Pretoria, and examined for the presence of rotaviruses to assess the
      potential for hospital-acquired infection in the paediatric wards. Stool samples
      were also collected from children admitted to the hospital for causes unrelated
      to gastro-enteritis to investigate the possible asymptomatic carriage of
      rotavirus in this population. Hospital-acquired rotavirus infection was
      determined in only 9% of cases. Very little asymptomatic carriage of the virus
      was identified. Electrophoretic analysis of the rotavirus strains showed that the
      majority of the infections (20 of 42) were associated with a particular strain
      with a long RNA profile, while 7 minor strains co-circulated (5 with a long
      electrophoretype and 2 with a short one). An apparent small outbreak of
      nosocomial infection with a single strain was observed to occur in one of the
      paediatric wards during the spring and early summer.

PMID- 8545752
TI  - Meconium aspiration in South Africa.
AB  - This retrospective study of 569 cases of meconium aspiration from 11 institutions
      in South Africa reveals a high incidence varying from 4 to 11/1,000 and a
      mortality rate of 12%. Mortality was significantly related to the degree of
      asphyxia at birth. Twenty-five per cent of the babies (136/569) required
      intensive care and 36% died. Of the mothers 18-25% were unbooked and most of the
      babies were inborn (87%). Babies born to primiparous mothers and to mothers over
      35 years of age were at greater risk of death. In order to reduce mortality and
      the numbers admitted to the intensive care unit simple measures for the reduction
      in the incidence of this disease need to be emphasised in all teaching and
      training programmes.

PMID- 8545753
TI  - Detection of human papillomavirus DNA with in situ hybridisation in oral squamous
      carcinoma in a rural black population.
AB  - Intra-oral carcinoma is the third most common malignancy among men in developing
      countries, and carries a high mortality rate, particularly in Africa, where
      patients often present initially with lesions at an advanced stage. The present
      study was undertaken to determine the prevalence of human papillomavirus (HPV)
      DNA in oral squamous carcinoma in the west of the Northern Transvaal, an area
      where a large number of new cases has been diagnosed over the past few years.
      Paraffin blocks from 66 cases (51 men, 15 women; mean age 58.7 years) of oral
      squamous carcinoma were randomly selected. Blocks contained samples of both
      tumour and adjacent normal epithelium. The presence of HPV antigen was
      established by means of immunocytochemistry and HPV DNA by in situ hybridisation
      with radiolabelled probes for HPV-6, 11, 16 and 18. Immunocytochemistry for viral
      antigen was negative in all the specimens. HPV-18 was detected in normal
      epithelium adjacent to the tumour in one case only. It appears from our study
      that HPV is of limited importance in oral squamous cell carcinogenesis in the
      population studied.

PMID- 8545754
TI  - Assessment of quality of life by clinicians--experience of a practical method in
      lung cancer patients.
AB  - OBJECTIVE: To evaluate a practical method (brief scale) of assessing the quality
      of life in patients with lung cancer. DESIGN: To compare the scores obtained by
      means of the brief scale with those obtained on formal tests. The brief scale
      consists of an Outlook score (measuring psychological status) and a Support score
      (measuring psychosocial support). The formal tests were the Hospital Anxiety and
      Depression Scale (HADS) for psychological status, and the Rotterdam Symptom
      Checklist (RSCL) and Spitzer QL-Index for quality-of-life assessment. SETTING:
      Lung cancer follow-up clinic, Groote Schuur Hospital. PARTICIPANTS: A total of 40
      patients selected by random sample. MAIN OUTCOME MEASURES: The correlation
      between the brief scale and standard formal tests. RESULTS: The HADS indicated
      that psychological morbidity was present in 30% of patients. Both the RSCL and
      the Spitzer QL-Index indicated a significantly poor quality of life in 25% of
      patients. The Outlook score correlated with both psychological status and quality
      of life. The Support score correlated with psychological status but not with the
      assessment of quality of life. It did, however, correlate with the independent
      evaluation of social support in the Spitzer QL-Index. CONCLUSIONS: The brief
      scale is a cost-effective and useful tool for quality of life assessment in the
      clinical management of patients with lung and other cancers.

PMID- 8545755
TI  - Epstein-Barr virus-induced systemic lupus erythematosus.
AB  - Evidence of virus-induced systemic lupus erythematosus (SLE) is illustrated by
      documentation of a 10-year old girl who developed SLE (satisfying ARA criteria)
      soon after infection with Epstein-Barr virus (EBV) infection. She showed complete
      remission 24 months later following an aggressive course of immunosuppressive
      therapy. The appearance and disappearance of serological evidence of EBV
      infection, followed by the onset and complete clinical and serological remission
      of SLE, which in this case had unusually mild complications, suggest a causal
      relationship.

PMID- 8545756
TI  - Uvulectomy--the making of a ritual.

PMID- 8545757
TI  - Restructuring of health services--the bullet bites back?

PMID- 8545758
TI  - The first heart transplant--background and circumstances.

PMID- 8545759
TI  - Audit of transfusion of red blood cells.

PMID- 8545760
TI  - Disability and rehabilitation--what are we teaching our future doctors?

PMID- 8545761
TI  - Limited private practice--the other issue.

PMID- 8545762
TI  - Cardiac transplantation in the private sector.

PMID- 8545763
TI  - Transmyocardial laser revascularisation.

PMID- 8545764
TI  - Quality of life and support of patients with lung cancer.

PMID- 8545765
TI  - Decentralisation of health services--problems and promises.

PMID- 8545766
TI  - Why patients do not arrive for booked gynaecological surgery.

PMID- 8545767
TI  - Screening for Down syndrome.

PMID- 8545768
TI  - Screening for Down syndrome.

PMID- 8545769
TI  - HIV in pregnancy--a policy needed.

PMID- 8545770
TI  - A neurosurgical call to arms: you can help.

PMID- 8545771
TI  - Prognostic factors in low-grade supratentorial astrocytomas: a uni-multivariate
      statistical analysis in 76 surgically treated adult patients.
AB  - A retrospective uni-multivariate statistical analysis was performed on 32
      prognostic factors to investigate their importance in predicting survival in a
      series of 76 adult patients with low-grade supratentorial astrocytomas treated
      over a 13-year period. The end point used for this study was the length of
      survival. The median survival time was 40 months. Overall actuarial survival at
      2, 5, and 10 years was 69%, 38%, and 22%, respectively. Radical resection of the
      neoformation, a higher preoperative Karnofsky performance status (KPS) score, and
      an age younger than 50 years are strongly correlated with survival; postoperative
      radiotherapy appears to be associated with increased survival only in patients
      under 50 years of age.

PMID- 8545772
TI  - Low-grade astrocytomas: prognosis factors and elements of management.
AB  - BACKGROUND: The literature provides information concerning prognosis of low-grade
      astrocytomas, but the series are quite heterogeneous in terms of clinical
      material, neuropathological evaluation, and statistical methods of analysis.
      Therapeutical indications are poorly defined. The last World Health Organization
      (WHO) histological classification provided a very precise definition of low-grade
      gliomas. METHODS: Taking into account a recent study of our own and literature
      data, management guidelines of these tumors were proposed. RESULTS: Grade I
      (pilocytic and subependymal giant cell astrocytomas) are surgically curable
      lesions. No adjuvant treatment is mandatory. Management of grade II astrocytomas
      is less clear-cut. Conservative management is probably possible in young patients
      without functional threat. The role of surgery on duration of survival has been
      properly established in very few series and was negative in many others. The role
      of radiotherapy has been demonstrated in a few subgroups of patients. In our
      study of ordinary astrocytomas, considering decades of age at diagnosis, survival
      curve analysis established three prognostic classes of age (before 50, between 50
      and 60, and after 60 years of age). Based on our results and on recently
      published data, a branch decisional approach was proposed for management of grade
      II astrocytomas. Other grade II gliomas exhibit more favorable prognoses but
      could be managed in the same manner. CONCLUSIONS: Ordinary grade II astrocytomas
      constitute a paradigm of difficult differential management. Further pertinent
      information on these tumors could come from the field of tumor biology, or be
      provided by very large and homogeneous groups of patients.

PMID- 8545773
TI  - Myelopathy associated with fibrocartilaginous emboli (FE): review and two
      suspected cases.
AB  - BACKGROUND: Myelopathy secondary to fibrocartilaginous emboli is rarely reported
      and has been documented antemortem only once. The pathophysiology of
      fibrocartilaginous emboli lacks consensus, although the role of trauma has been
      previously entertained. METHODS: We reviewed the reported cases of myelopathy
      secondary to fibrocartilaginous emboli. We extensively evaluated two cases of
      myelopathy in otherwise healthy individuals using myelography and serial magnetic
      resonance imaging (MRI). Evaluation for underlying systemic disease was conducted
      in both cases. RESULTS: No evidence of infectious, autoimmune, inflammatory, or
      neoplastic disease was found in either patient. Furthermore, no other lesions
      were found in the neuroaxis. Findings on serial MRIs were consistent with
      vascular lesions thought to be venous strokes. CONCLUSIONS: We report two cases
      of acute myelopathies associated with heavy lifting, in otherwise healthy young
      men. Serial MRI studies in each case demonstrated lesions consistent with venous
      infarcts. We postulate that migration of disc material into the perivertebral
      venous system was the result of increased intervertebral disc pressure and
      simultaneous excessive Valsalva associated with heavy lifting. We further
      postulate that this may be a more prevalent cause of acute myelopathy than
      previously recognized.

PMID- 8545774
TI  - Cervical central cord syndrome involving the spinal trigeminal nucleus: a case
      report.
AB  - BACKGROUND: Central cord syndrome is a commonly encountered disease entity. Its
      underlying pathophysiology, however, is not well understood. METHODS: A 20-year
      old patient with cervical injury with an atypical symptom of burning sensation in
      the face and neck area is reported. RESULTS: The initial burning sensation in the
      face retreated from the center towards the periphery according to the "onionskin"
      segmentation of facial dermatomes, which suggested some pathologic condition
      residing in the spinal trigeminal nucleus. CONCLUSIONS: The findings of this case
      suggest that the main locus of pathologic process of the central cord syndrome is
      in the gray matter rather than the white matter.

PMID- 8545775
TI  - Intramedullary tuberculoma: report of two cases with MRI findings.
AB  - Two cases of spinal intramedullary tuberculous granulomas (tuberculomas) without
      any bony involvement are reported. The rarity of the occurrence and the magnetic
      resonance imaging (MRI) findings are discussed. Microsurgical excision and
      antituberculous treatment produced good results.

PMID- 8545776
TI  - Anastomosis of occipital artery to posterior cerebral artery with interposition
      of superficial temporal artery using occipital interhemispheric transtentorial
      approach: case report.
AB  - BACKGROUND: Superficial temporal artery (STA)-superior cerebellar artery (SCA)
      anastomosis, and STA-posterior cerebral artery (PCA) anastomosis are considered
      suitable as surgical procedures for the treatment of patients with significant
      stenosis or occlusion in the rostral portion of the basilar artery and patients
      with significant stenosis or occlusion of the posterior cerebral artery,
      respectively. However, several authors have reported frequent and serious
      complications of these surgical procedures, including temporal lobe retraction
      edema and hematoma. In this study, we introduce a new surgical revascularization
      using an occipital interhemispheric transtentorial approach for the treatment of
      severe stenosis of the rostral portion of the basilar artery. CASE REPORT: A 47
      year-old man with hypertension noted the sudden onset of nuchal pain followed by
      vertigo, diplopia, drunken gait, and motor weakness on his right side.
      Angiography performed on the day of the onset disclosed severe stenosis of the
      basilar artery. The stenotic portion extended just distal to the anterior
      inferior cerebellar artery (AICA) to just proximal to the SCA, and in addition, a
      pseudolumen was visualized just distal to the left AICA. The patient underwent
      right occipital artery (OA) to left PCA anastomosis with interposition of the STA
      using an occipital interhemispheric transtentorial approach. Marked improvement
      in dysarthria, diplopia, ataxia gait, and visual disturbance were noted and he
      was able to walk without aid 3 days after operation. A postoperative angiogram of
      the right OA obtained 25 days after operation demonstrated visualization of the
      left PCA via the anastomosed OA and STA graft. CONCLUSIONS: OA-PCA anastomosis
      with interposition of STA graft using an occipital interhemispheric
      transtentorial approach can be substituted for STA-SCA anastomosis and STA-PCA
      anastomosis for treatment of stenosis/occlusion of the rostral portion of the
      basilar artery.

PMID- 8545777
TI  - Evaluation of cerebral blood flow and hemodynamic reserve in symptomatic moyamoya
      disease using stable Xenon-CT blood flow.
AB  - Moyamoya disease is a vascular abnormality seen in children and adults
      characterized by progressive narrowing of the internal carotid, middle, anterior,
      and posterior cerebral arteries and the development of leptomeningeal and
      proximal internal carotid artery collaterals, which appear diaphanous on
      angiogram. Although adults tend to present with subarachnoid hemorrhage and
      children with ischemic events, the clinical sequelae in these two populations
      overlap. Expanding upon work done at this institution using stable xenon computer
      tomographic blood flow determinations with acetazolamide and carbon dioxide
      challenge to predict which population of patients with severe carotid disease and
      hemodynamic compromise would benefit from surgical intervention, we used similar
      rationale to determine which patients with moyamoya disease would likely benefit
      from revascularization. Data and outcome concerning four such patients make up
      the body of this report.

PMID- 8545778
TI  - Surgical treatment of a cerebral mycotic aneurysm using the stereo-angiographic
      localizer.
AB  - The authors report a case of mycotic aneurysm surgically treated by means of the
      Suetens-Gybels-Vandermeulen angiographic localizer system. The major advantages
      of this technique are reported.

PMID- 8545779
TI  - Computerized tomography (CT) localized stereotactic craniotomy for excision of a
      bacterial intracranial aneurysm.
AB  - BACKGROUND: The treatment of bacterial intracranial aneurysms include long-term
      antibiotic therapy and surgical clipping or resection. Direct surgical approaches
      to these aneurysms are often complicated by their peripheral location. METHODS:
      We report the use of a computerized tomography (CT) localized stereotactic
      craniotomy for the excision of a ruptured peripheral bacterial intracranial
      aneurysm. RESULTS: The Leksell Steiner-Lindquist microsurgical guide, with its
      fiberoptic helium-neon laser, allowed for rapid isolation of the distal aneurysm
      with minimal cerebral dissection. Since the inflammatory lesion was well
      demonstrated on postcontrast CT scan, this modality, rather than angiography, was
      used for localization. CONCLUSIONS: In the future, stereotactic craniotomy may
      facilitate aggressive surgical therapy for infectious aneurysms previously
      thought not suitable for direct operative approach.

PMID- 8545780
TI  - Anticoagulation for prevention of cerebral infarcts following subarachnoid
      hemorrhage.
AB  - BACKGROUND: Late neurologic deterioration following subarachnoid hemorrhage is
      often due to vasospasm and rebleeding. Although the sudden onset of a focal
      neurologic deficit can actually be the result of thromboembolism, anticoagulation
      has rarely been used in such cases. METHODS: We report a case of a 55-year-old
      woman who developed recurrent transient focal neurologic deficits 13 days after
      having a subarachnoid hemorrhage, with multiple cerebral infarcts by CT. Two
      cerebral angiograms showed no aneurysm. Her symptoms and clinical temporal
      profile were consistent with thromboembolic phenomenon. We elected to treat her
      with systemic anticoagulation. RESULTS: The patient had no recurrent events after
      systemic anticoagulation, but had episodic sensory changes and a new infarct on
      MRI once the anticoagulation was discontinued. CONCLUSIONS: Anticoagulant was
      safely administered after subarachnoid hemorrhage (SAH) in this patient and may
      have been effective in preventing further cerebral ischemic infarction following
      her SAH. Our patient's clinical profile of sudden (rather than gradual) onset of
      a transient focal neurologic deficit and resolution of blood on CT indicates one
      setting in which the use of heparin may be considered.

PMID- 8545781
TI  - Subarachnoid and intraventricular hemorrhage caused by hypernephroma metastasis,
      accompanied by innocent bilateral posterior communicating artery aneurysms.
AB  - We present a case of subarachnoid and intraventricular hemorrhage due to an
      infratentorial metastasis of a renal cell carcinoma. The lesion was not apparent
      on initial magnetic resonance imaging (MRI) or in a follow-up examination (MRI
      and angiography) 6 weeks after the bleeding. The innocent bilateral posterior
      communicating artery aneurysms detected by cerebral angiography were treated
      surgically. The origin of the hemorrhage, however, remained unclear. Five months
      later, a surgically proven metastasis in the fourth ventricle subsequently gave
      the explanation for the bleeding.

PMID- 8545782
TI  - The juxtacondylar approach to the jugular foramen (without petrous bone
      drilling).
AB  - BACKGROUND: Surgical access to the jugular foramen is generally realized through
      the infratemporal approach, requires petrous bone drilling with facial nerve
      exposure and sometimes transposition. This is a rather complex and time-consuming
      technique that exposes the patient to complications such as deafness and facial
      nerve palsy. METHODS: The juxtacondylar approach we propose in this paper needs
      only a partial mastoidectomy and exposure of the distal cervical segment of the
      vertebral artery (above C2). The transverse process of the atlas is completely
      removed so as to permit progress upward along the lateral mass of the atlas and
      the occipital condyle. The vertebral artery rarely has to be transposed. RESULTS:
      The main indication for the juxtacondylar approach is neurinoma and meningioma of
      the jugular foramen. For tumors like paraganglioma extending into the petrous
      bone, the juxtacondylar approach can be combined with an infratemporal approach.
      The juxtacondylar approach has been used in seven cases including three
      neurinomas, three paragangliomas and one meningioma. Exposure was quite
      satisfactory on both intra- and extradural parts in all cases. CONCLUSIONS: The
      juxtacondylar approach is a different way to expose the jugular foramen region.
      Compared to the standard infratemporal approach, it is a complementary rather
      than an alternative technique; the exposure is rather on the posteroinferior side
      for the juxtacondylar approach and on the anterosuperior side for the
      infratemporal approach.

PMID- 8545783
TI  - Periventricular lucency on computed tomography associated with hydrocephalus:
      what is the cause?

PMID- 8545784
TI  - Is "conservative" really the opposite of "surgical"?

PMID- 8545785
TI  - Doctor Cushing as I knew him.

PMID- 8545786
TI  - Have neurosurgeons lost their chance to treat the patient with spine problems,
      vascular disease, and peripheral nerve problems?

PMID- 8545787
TI  - [Intra-arterial treatment of therapy-resistant residual tumors of the pelvis].
AB  - PURPOSE: Evaluation of intraarterial cancer treatment in recurrent pelvic tumors,
      which were resistent to other treatment modalities. PATIENTS AND METHODS: Ninety
      seven patients suffering from pelvic recurrences originating from bladder (n =
      40), rectum (n = 19), cervix (n = 21) oder other organs (n = 17) were treated by
      intraarterial chemotherapy (111 times) or transcatheter embolisation (52 times).
      RESULTS: Less than 20% of our patients had remission of the tumor burden but
      tumor symptoms (especially pain and bleeding) could be controlled in 35 to 87% of
      the patients. The main complication was a muscle necrosis after intraarterial
      chemotherapy because of recurrent bladder cancer. CONCLUSION: Intraarterial
      cancertherapy is a useful procedure for symptomatic treatment of tumor symptoms
      especially in case of bleeding. Local tumor control can only be achived in a
      minority of the patients.

PMID- 8545788
TI  - [Low-dose radiotherapy of localized prostate neoplasms: How low is high enough?].
AB  - BACKGROUND: According to the American Patterns of Care Studies, at least 70 Gy
      are required to achieve local control of large or undifferentiated carcinomas of
      the prostate. More recent data on repeated measurements of the prostate-specific
      antigen (PSA) cast doubt on the radiocurability of tumors with markedly elevated
      PSA. PATIENTS AND METHODS: With a retrospective analysis, the treatment results
      of local radiotherapy to mid-sized pelvic volumes with a median dose of 66 Gy
      (1979 to 1988, n = 118) are compared to the outcome after radiotherapy to small
      prostatic volumes with a median dose of 70.2 Gy (1989 to 1992, n = 126). RESULTS:
      Overall survival at 5 years was 65.9% and 82.3%, respectively. Patients treated
      at a later time had the same life expectancy as expected for the normal
      population. Distant disease-free survival was identical in both groups (70.4 and
      74.3% at five years). Local control could not be assessed by digital rectal
      examination in a large part of the patients. However, in 50 patients without any
      pretreatment, the course of PSA was followed. Pretreatment values of > 30 ng/ml
      were highly predictive for "biochemical relapse" (rising values) within 2 years.
      Despite individual shielding of the rectum, the rate of symptomatic proctitis
      rose from 1.7% to 5.6% in patients treated 1989 to 1992. CONCLUSIONS: We found no
      negative impact of decreasing the target volume on the overall and distant
      disease-free survival. The rate of symptomatic proctitis has increased with
      higher target doses despite better shielding of the rectum, but has remained
      within an acceptable range. Considering the high rate of biochemical relapse and
      therefore the poor prognosis associated with initial PSA values > 30 ng/ml, the
      application of a potentially toxic dose of > 70 Gy in these patients seems hardly
      justified.

PMID- 8545789
TI  - [Improvement of interstitial brachytherapy for localized prostate neoplasms with
      a new implantation technique].
AB  - PURPOSE: The success of an interstitial brachytherapy treatment is based on the
      correct implantation geometry. Frequently, deviations of top needle vs. template
      coordinates were observed by transrectal sonography of 358 high-dose-rate (HDR)
      implantations for prostate cancer. PATIENTS AND METHODS: In cooperation with the
      companies BIP GmbH and Isotopen-Technik Dr. Sauerwein GmbH we developed a high
      speed implantation machine, which was tested by 22 interstitial prostate
      applications. We compared the manual needle positioning method to the high-speed
      machine and observed the sequence of needle deviation as well as the acute
      postoperative side effects (hematoma, macroscopic hematuria, pain and urin stop).
      RESULTS: Using the manual implantation method (n = 12) 43.8% of all implanted
      needles (42 out of 96, mean 3.5) showed a deviation vs. 3.6% (3 out of 83, mean
      0.3) by the use of the high-speed device (n = 10). Acute postoperative side
      effects according to the implantation were: urin stop (3 vs. 0), macroscopic
      hematuria (3 vs. 1), and pain (4 vs. 1), respectively. CONCLUSION: The use of a
      modified high-speed biopsy device for the interstitial brachytherapy results in a
      higher accuracy in the needle positioning and in reproducing pretreatment
      implantation plans. Because of the good clinical experience we introduced the
      high-speed implantation device into our clinical routine.

PMID- 8545790
TI  - [Simultaneous radiochemotherapy in recurrent and metastatic breast neoplasm.
      Clinical experience].
AB  - BACKGROUND: To improve the quality of life for patients with recurrent and
      metastatic breast cancer, palliation of pain, skin and soft tissue metastases and
      complicating lymph node relapses are mandatory. Toxicity and efficacy of 2
      simultaneous radiochemotherapy regimens was tested in this study. PATIENTS AND
      METHODS: From October 1989 to March 1993, 48 patients with locoregional relapse
      of breast carcinoma after primary mastectomy and no option for curative resection
      were entered in the study. Seventeen patients had additional distant metastases.
      Two different radiochemotherapy regimens were applied: Group A (28 patients)
      received a "split course" radiotherapy within 10 weeks (1.8 to 2 Gy single dose)
      on day 1 to 12, 29 to 40 and 57 to 68 up to a total dose of 54 Gy. Chemotherapy
      with 5-FU, methotrexate and cyclophosphamide was applied simultaneously with
      radiation. After the second and fourth week the treatment was interrupted for 2
      weeks. Group B (20 patients) received "conventional" radiotherapy over 6 weeks
      with 1.8 to 2 Gy single and 54 Gy total dose. 5-FU and mitomycin C was applied in
      the first and fifth week of radiotherapy. Treatment toxicity was analyzed in 48
      patients, while treatment efficacy was assessed in 44 patients with a minimum
      follow-up of at least 1 year. RESULTS: Overall treatment response (CR+PR) was 82%
      in group A (CR 21%). Five of 28 patients developed toxicities of grade 3 to 4
      (EORTC/RTOG/WHO). The overall response rate in group B was 87% (CR 19%). In this
      group 6 of 20 patients experienced toxicities of grade 3 to 4. In both groups,
      the local response rate was remarkably reduced in patients with additional
      visceral metastases. CONCLUSIONS: Both treatment concepts achieved similar
      response rates. Group B patients experienced a higher toxicity rate, but
      treatment duration was considerably shorter. The local response rate correlated
      well with the extent of systemic metastatic disease.

PMID- 8545791
TI  - Is veno-occlusive disease incidence influenced by the total-body irradiation
      technique?
AB  - BACKGROUND: In order to assess the influence of total-body irradiation technique
      on veno-occlusive disease (VOD) incidence, we retrospectively analyzed our
      leukemia patients treated with bone-marrow transplantation conditioned using
      total-body irradiation and high-dose chemotherapy. PATIENTS AND METHODS: Between
      1980 and 1992, 305 patients with acute non-lymphoblastic leukemia (ANLL; n = 170)
      and acute lymphoblastic leukemia (ALL; n = 135) were treated with bone-marrow
      transplantation in their first complete remission (CR; n = 223) or in second CR
      (n = 82). All patients underwent total-body irradiation either in single dose (n
      = 176; 10 Gy to L4, 8 Gy to the lungs) or in 6 fractions (n = 129; 12 Gy in 3
      consecutive days to L4, 9 Gy to the lungs) before bone-marrow transplantation.
      Patients were analyzed in 2 instantaneous dose rate groups: 104 (34%) patients
      received an instantaneous dose rate < or = 4.80 cGy/min (mean: 3.07 +/- 0.60
      cGy/min), and 201 (66%) > 4.80 cGy/min (mean: 6.60 cGy/min +/- 0.30).
      Conditioning chemotherapy consisted of cyclophosphamide alone in 231 patients,
      cyclophosphamide and etoposide or melphalan in 53 patients, and 21 patients were
      conditioned with cytosine arabinoside and melphalan. Bone-marrow transplantation
      was autologous in 197 patients, and allogeneic in 108 patients. RESULTS: Thirty
      (10%) of the 305 patients experienced VOD. In univariate analyses, its incidence
      was not influenced by instantaneous dose rate (9.6% [10/104] in < or = 4.80
      cGy/min group vs. 10% [20/201] in > 4.80 cGy/min group; p = 0.91), fractionation
      (11% [19/176] in single-dose total-body irradiation vs. 8.5% [11/129] in
      fractionated total-body irradiation, p = 0.64), age (9% [21/241] in < or = 40
      year old-patients vs. 14% [9/64] in > 40-year-old patients, p = 0.29), sex (6%
      [7/113] in male patients vs. 12% [23/192] in female patients, p = 0.15), type of
      VOD prevention (16% [16/101] in patients using heparin vs. 10% [14/142] in those
      receiving dinoprostone and pentoxifylline combination, p = 0.23), type of bone
      marrow transplantation (9% [10/108] in allogeneic bone-marrow transplantation
      group vs. 10% [20/197] in autologous bone-marrow transplantation group, p =
      0.96), or type of acute leukemia (9.6% [13/135] in ALL vs. 10% [17/170] in ANLL,
      p = 0.93). However, VOD incidence was significantly lower in patients whose
      conditioning chemotherapy consisted of cyclophosphamide alone (6.5% [15/231] vs.
      20% [15/74] by other drugs +/- cyclophosphamide, p < 0.0001), and in patients
      treated after 1985 (7% [16/226] vs. 18% [14/79] in those treated before 1985, p =
      0.01). Multivariate logistic regression analysis revealed that the best
      independent factors influencing the occurrence of VOD were the male sex (p =
      0.03), conditioning chemotherapy consisting of cyclophosphamide alone (p = 0.01),
      and bone-marrow transplantation after 1985 (p = 0.008). CONCLUSION: In our series
      of 305 acute leukemia patients treated with allogenic or autologous bone-marrow
      transplantation, total-body irradiation technique (fractionation or instantaneous
      dose rate) did not seem to influence the incidence of VOD.

PMID- 8545792
TI  - [Representation and transfer of labeled reference structures in X-ray, CT and MR
      imaging].
AB  - PURPOSE: Image information obtained with different methods should be exactly
      transferable to profit fully from the single advantage the different imaging
      method has in localisation and for further treatment planning. Prominent
      anatomical points serve as reference structures (landmarks) for the transference
      of imaging information and details of situation. Aim of this study is the
      improvement of reproductability by comparing topographic relations, measurements
      and positioning in different imaging-procedures with supporting marking
      aids/surface markers. MATERIAL AND METHODS: By using pharmacological capsules and
      plastic tubes filled with oily contrast medium containing iodine (Lipiodol; Byk
      Gulden), marking aids were developed which can be seen in similar definite limits
      within the framework of MRI-, CT- and conventional X-ray-Imaging. RESULTS: A
      method to view these new, artificial markers in combination with individual,
      anatomical landmarks is introduced. The marking aid/surface marker, fixed on
      anatomical reference structures on the skin, does not result in an additional
      burden for the patient. CONCLUSIONS: The new, artificial markers are also useful
      for making other structures recognizable, such as anatomical relation lines,
      center of the portal and edges in planning imaging for radiotherapy treatments
      and are used as leading and reference structures to compare localisation and
      extent of lesions in X-ray-, CT- and MRI. Marking aids/surface markers do not
      have to be changed in different imaging methods.

PMID- 8545793
TI  - [Radiotherapy of malignant lymphomas of the brain: Radiologic behavior in
      relation to radiation dose and volume].
AB  - PURPOSE: During the radiotherapy of malignant CNS-lymphomas computertomographic
      controls were performed as a routine. The radiologic results should give a base
      to define the total dose. The aim was to determine the value of such individual
      parameters. PATIENTS AND METHODS: Fourteen years ago the prospectively defined
      treatment concept included a parallel opposed whole brain irradiation slowly
      increasing with 1 x 1.0 Gy, 1 x 1.5 Gy, 1 x 2.0 Gy, then 10 x 3 Gy, followed by a
      radiological control and whenever possible a boost to the initially involved
      region with 7 to 10 x 2 Gy. RESULTS: From 1. 1. 1979 to 31. 12. 1993 28 patients
      with a malignant non-Hodgkin-lymphoma of the brain have been seen at the state
      hospital in Aarau. Fifteen cases suffered from a primary involvement of the
      brain, 13 showed a secondary manifestation. 20/28 (71%) presented radiologically,
      cytologically or at autopsy as multifocal disease. Histologic examination mainly
      detected intermediate or high-grade lymphomas. 25 patients have been irradiated.
      In 4 out of them the radiation concept couldn't be realized. CT-results were as
      follows: after 30 to 40 Gy: CR = 2/21 (9.5%); after 45 to 55 Gy: CR = 10/19
      (53%); after 1 to 3 months: CR = 12/15 (80%). Nine local relapses occurred, 3 out
      of them regrowed multifocally and therefore were detected also within the boost
      region. Six recurrences were outside in the lower dosed areas. No severe side
      effects have been observed. CONCLUSIONS: Most of the tumors disappeared
      radiologically not before 1 to 3 months after radiation. Recurrences are mainly
      seen in the lower dosed region. The incidence and the localisation of the
      recurrences give some reason to the idea, that the computertomography of these
      tumors does not detect properly there prior extensions.

PMID- 8545794
TI  - [Centennial of X-ray. Comments on its history, presence and future of its
      therapeutic application].

PMID- 8545795
TI  - [Indications for radical prostatectomy in the US].

PMID- 8545796
TI  - [Treatment sequelae following definitive percutaneous radiotherapy of prostatic
      neoplasms].

PMID- 8545797
TI  - [Results of treatment and quality of life after radical prostatectomy].

PMID- 8545798
TI  - [Adjuvant chemotherapy improves survival in head and neck tumors].

PMID- 8545799
TI  - Amblyopia.
AB  - Over the past thirty years, much has been learned about the physiological basis
      for amblyopia. For many years amblyopia was considered to be a retinal disorder;
      it has now been well established through animal studies that amblyopia represents
      functional and morphological effects of visual deprivation on the visual cortex
      and the lateral geniculate nucleus. With this knowledge has come the recognition
      of a "sensitive period" of development of the visual system, during which time
      visual deprivation causes amblyopia. The best approach to managing amblyopia is
      to detect amblyogenic factors before the age of two years and prevent it through
      eliminating the causes of visual deprivation. When amblyopia exists, it can be
      cured if adequately treated in children less than 6-7 years of age. Even in older
      patients, visual improvement can be achieved with therapy. Current research is
      aimed at developing substances and delivery modes that will allow the sensitive
      period of visual development to be manipulated, increasing the period during
      which it can develop and enhancing preventative and therapeutic measures. In this
      review selected literature contributing to current understanding of causes,
      prevention and treatment of amblyopia is discussed. Although many new treatment
      modalities have been tried, occlusion still seems to be the most successful
      therapy.

PMID- 8545800
TI  - Fundus manifestations of orbital disease and treatment of orbital disease.
AB  - Disorders of the orbit can secondarily involve the eye. Although nonspecific,
      changes which can be noted on funduscopic examination including abnormalities of
      the retina, choroid, and optic nerve, can be secondary to an underlying orbital
      process. Awareness of these findings and their association with orbital disease
      is of great importance to the practicing ophthalmologist, since many orbital
      disorders are treatable and indeed, some are life-threatening. In addition,
      treatment of these disorders can potentially result in a variety of ocular
      complications. An understanding of the potential risks is of the utmost
      importance in planning treatment of an orbital disease.

PMID- 8545801
TI  - Preventing blindness in Americans: the need for eye health education.
AB  - Black Americans are twice as likely to be blind as their white counterparts.
      Although blindness is preventable or curable in half of the patients studied, we
      have found that black Americans are only half as likely to be treated for
      glaucoma or cataract, which are the two leading causes of blindness in this
      population. Our data show that this treatment gap is not related to the supply of
      ophthalmologists or the patients' personal income, even among insured
      populations. In addition to the devastating financial costs incurred by blind
      individuals and their families, a single year of blindness for a working age
      American costs the federal government approximately $12,000. Research has shown
      that preventing blindness is often less expensive, in simple economic terms, than
      paying for the costs a blind individual incurs. These findings raise important
      questions about access to care and how it may improve within the context of
      health care reform. Government surveys show that black Americans, even those with
      health insurance, are significantly less likely to seek or obtain examination by
      an ophthalmologist. In studying utilization of care, we found that, in aggregate,
      black Americans who see an ophthalmologist are as likely as their white
      counterparts to be treated for glaucoma, cataract, and other blinding diseases.
      We propose that, beyond universal access to health insurance, eye health
      education that influences people to see an ophthalmologist may be the single most
      important step we can take to prevent needless blindness. Not only can education
      and preventive eye care save needless suffering, it may save scarce federal
      dollars as well.

PMID- 8545802
TI  - Does a tilted retina cause astigmatism? The ocular imagery and the retinoscopic
      reflex resulting from a tilted retina.
AB  - An astigmatic dial viewed by a tilted retina will have only one line in focus,
      simulating astigmatic blur. We compare and contrast this optical situation to
      actual astigmatism. Photographs were taken of an astigmatic dial blurred with a
      cylindrical lens, and also of the same astigmatic dial tilted, simulating tilted
      retinal imagery. A model eye for retinoscopy practice was provided with a retina
      tilted 30 degrees and was retinoscoped repeatedly with and without added
      confounding cylinder by five skilled retinoscopists. Photographs of the
      astigmatically blurred and tilted astigmatic dials were similar but not
      identical, as expected. The model eye with tilted retina showed no astigmatism by
      retinoscopy in 14/15 measurements and 0.25 D of astigmatism in one measurement.
      When confounding cylinder was present, the retinoscopic measurement was always
      within 0.25 D of the added cylinder. The ocular imagery resulting from a tilted
      retina can simulate astigmatic blur, but this is actually due to a type of
      curvature of field. Only a minute area of the tilted retina is viewed during
      retinoscopy, so the tilt has essentially no influence on the retinoscopic reflex.

PMID- 8545803
TI  - Genetic and molecular studies of macular dystrophies: recent developments.
AB  - Macular degeneration is a heterogeneous group of disorders characterized by
      progressive central visual loss and degeneration of the macula and underlying
      retinal pigment epithelium (RPE) of the eye. Age-related macular degeneration
      (ARMD), the most common form of the disease, is the leading cause of legal
      blindness in the elderly population in the United States and in the many
      developed countries throughout the world. Despite its prevalence, its etiology
      and pathogenesis are poorly understood, and effective treatment options are
      limited for most patients. Inherited macular dystrophies share many important
      features with ARMD but are more readily studied by molecular genetic approaches.
      Over the past few years, significant progress has been made in the molecular
      genetics of inherited macular dystrophies. Genes responsible for dominant and
      recessive Stargardt's macular dystrophy as well as Best's disease have been
      localized to specific chromosomal regions. The peripherin/RDS gene when defective
      is associated with butterfly-shaped pattern dystrophy. Molecular studies of genes
      involved in macular dystrophies may yield insights into the mechanisms of
      pathogenesis of macular degeneration and provide new rationale for the management
      and treatment of patients with these diseases.

PMID- 8545804
TI  - Visual loss following treatment of sphenoid sinus carcinoma.
AB  - A 71-year-old woman developed complete third nerve palsy and total blindness of
      the right eye one month after completing a course of radiotherapy for sphenoid
      sinus carcinoma over a 13-month period. Differential diagnosis included
      recurrence of the tumor, radiation-induced second neoplasm, empty sella with
      chiasmal prolapse and secondary chiasmal arachnoid adhesions, and radionecrosis.
      Magnetic resonance imaging demonstrated gadolinium contrast enhancement of the
      right intracranial optic nerve and chiasm, suggesting a radionecrosis process.

PMID- 8545806
TI  - Glimpses of my mentor, Sir Stewart Duke-Elder.
AB  - The author writes not as a biographer, but as a longtime colleague and close
      friend of Sir Stewart Duke-Elder. Unique anecdotes elucidate the personality of
      this great ophthalmologist, teacher and writer.

PMID- 8545805
TI  - Credibility: the key to the successful physician witness.
AB  - A doctor's personal credibility is the paramount factor in achieving success when
      testifying, especially as a defendant. Factors that aid credibility include a
      natural manner, sincerity, confidence, clarity and composure. Being
      argumentative, defensive, smug, flamboyant, or nervous undermines credibility.
      The authors offer advice to enhance the ophthalmologist's success in testifying.

PMID- 8545807
TI  - Assessment of the infectivity of corneal buttons taken from hepatitis B surface
      antigen seropositive donors.

PMID- 8545808
TI  - Treatment of corneal dystrophies with excimer laser.

PMID- 8545809
TI  - Preliminary results with a new hydrogel intraocular lens.

PMID- 8545810
TI  - The influence of magnesium on visual field and peripheral vasospasm in glaucoma.

PMID- 8545811
TI  - Efficacy of apraclonidine ophthalmic solution (iopidine) in presumed silicon oil
      induced glaucoma and primary open-angle glaucoma.

PMID- 8545812
TI  - Checking for globe perforation after retrobulbar injection.

PMID- 8545814
TI  - The workers' comp monolith. Despite improvements, problems still remain.
AB  - For many Texas physicians, the workers' compensation system represents a
      bureaucratic tangle of regulations, guidelines, and forms; frequent payment
      hassles; and a cumbersome dispute-resolution process. If it were not for their
      concern for their patients' welfare, many of them would choose not to
      participate.

PMID- 8545813
TI  - Pickwickian syndrome and indications for surgically induced weight loss.

PMID- 8545815
TI  - Gene therapy uproar. Texas researchers say pessimism is unfounded.
AB  - When the New England Journal of Medicine published articles in late September
      showing that two gene therapy studies involving muscular dystrophy and cystic
      fibrosis patients had not produced positive results, the so-called "failure" was
      widely reported in the news media, sometimes in funeral tones. The reports
      created a distinct impression that researchers trying to find ways to use gene
      therapy techniques to treat a wide variety of diseases had made promises they
      could not keep.

PMID- 8545816
TI  - Religion's role in health. What's God got to do with it?
AB  - Sex, politics, and religion were once polite-conversation no-no's. But as
      Victorian sensibilities gave way to modern ones, society has loosened up, leaving
      few value-laden topics taboo. Government's regulatory grip on health care has
      made any comprehensive discussion of medicine incomplete without some mention of
      politics. Epidemic rates of AIDS and sexually transmitted diseases have forced
      medicine's participation in debates about sexuality. But religion has remained
      pretty much a nontopic, scientifically speaking, until relatively recently.

PMID- 8545817
TI  - A doctor's journey to the world of faith.

PMID- 8545818
TI  - Slam-dunked. New law forces insurance carriers to reduce rates.
AB  - No one saw it coming. Not consumer groups, not business or special interest
      groups, and especially not insurance carriers. The Texas Legislature did
      something this session no legislature had ever done, experts say. It ordered
      insurance carriers to cut premiums in practically all insurance lines, and for
      physicians, this will mean a 10% reduction in medical professional liability
      premiums effective January 1, 1996. Hospitals will see a 13% cut.

PMID- 8545820
TI  - Physicians need to know disabled parking guidelines.

PMID- 8545821
TI  - Maternal age, marital status may affect infant mortality.

PMID- 8545822
TI  - Difference is significant between bureaucratic regulation and individual right to
      sue.

PMID- 8545823
TI  - Formation of paramagnetic chromium in liver of mice treated with dichromate (VI).
AB  - The formation of paramagnetic chromium in the liver of male mice dosed with
      K2Cr2O7 (10, 20, and 40 mg Cr/kg) by a single ip injection was investigated by
      electron spin resonance (ESR) spectrometry. Both Cr(V) and Cr(III) complexes were
      detected in the mice livers at 15 min to 12 hr after Cr(VI) injection. The time
      course (15 min-12 hr) for the formation of paramagnetic Cr revealed that the
      hepatic levels of Cr(V) complexes decreased quickly during the first hour but
      decreased more slowly over the next 11 hr. However, in contrast to Cr(V), Cr(III)
      complexes appeared to persist for 12 hr after Cr(VI) treatment based on figures
      of Cr(III) signal. Thus, Cr(III) may be the ultimate form following reduction of
      Cr(VI) in liver. The total Cr content in liver of mice dosed with dichromate was
      also increased in a dose-dependent fashion (10-40 mg Cr/kg). However, Cr content
      in liver remained at similar levels for 15 min-6 hr, and slightly decreased at 12
      hr after Cr(VI) injection. Under the same experimental conditions,
      hepatotoxicity, as estimated by the increase of serum ornithine carbamyl
      transferase activity, appeared at 3 hr after 20 and 40 mg Cr/kg of Cr(VI)
      injection, while 10 mg Cr/kg of Cr(VI) produced no hepatotoxicity even at 12 hr.
      Predosing with phenobarbital, which increased the hepatic levels of cytochrome
      P450, resulted in a decrease of the levels of Cr(V) and in a small increase of Cr
      content, without affecting Cr(VI) hepatotoxicity. On the other hand, pretreatment
      with buthionine sulfoximine, which depleted hepatic glutathione (GSH) levels,
      caused a decrease of Cr(VI) hepatotoxicity, but the levels of Cr(V) and Cr in the
      liver remained unchanged. These results demonstrated that in vivo formation of
      paramagnetic Cr, in particular Cr(V), in liver of mice is clearly detected and
      quantified by ESR spectrometry and that hepatic levels of cytochrome P450 and GSH
      are associated with the induction of biological effects by Cr(VI) in liver in
      vivo. The results also suggested that the formation of Cr(V) was not the only
      mechanism involved in the induction of hepatotoxicity by Cr(VI) compounds.

PMID- 8545824
TI  - Comparative in vitro methylation of trivalent and pentavalent arsenicals.
AB  - The time course and extent of methylation of 1 microM arsenite (iAsIII), arsenate
      (iAsV), methylarsenite (MeAsIII), methylarsenate (MeAsV), and MeAsIII
      diglutathione complex (MeAsIII(GS)2) were examined in an in vitro assay system
      that contained rat liver cytosol. Precursor arsenicals and methylated metabolites
      were analyzed by thin-layer chromatography (TLC) or by hydride generation-atomic
      absorption spectrophotomoetry (HG-AAS). More than 90% of iAsIII was converted to
      a dimethylated species (Me2As) during a 90-min incubation at 37 degrees C; the
      amount of monomethylated metabolite was maximal at 15 min. In contrast, only 40%
      of iAsV was dimethylated during a 90-min incubation. Comparison of the yields of
      methylated species in the whole in vitro assay system as determined by HG-AAS and
      in an ultrafiltrate prepared from the in vitro assay system as determined by TLC
      indicated that nearly 70% of the dimethylated metabolite (possibly Me2AsIII) that
      was produced during a 90-min incubation was bound to proteins (> 10 kDa). The
      percentage of protein-bound arsenic in the assay system incubated at 0 degree C
      with trivalent arsenicals was three-to fivefold greater than the binding of
      corresponding pentavalent species. This indicated that both iAsIII and trivalent
      organoarsenicals interact avidly with proteins. Both MeAsIII prepared by
      metabisulfite-thiosulfate reduction of MeAsV and a MeAsIII(GS)2 were
      quantitatively converted to Me2As during 90-min incubation. In contrast, only 3%
      of MeAsV was dimethylated during this interval. These results suggest that
      trivalent arsenicals are preferred substrates for methylation reactions and that
      the reduction of As from pentavalent to trivalent states may be a critical step
      in the control of the rate of metabolism of As.

PMID- 8545825
TI  - In vivo modulation of the rat cytochrome P450 1A1 by double-stranded
      phosphorothioate oligodeoxynucleotides.
AB  - CYP1A1 gene expression is regulated by known cis- and transacting elements
      controlling inhibition and induction of CYP1A1 transcription. The influence of a
      double-stranded phosphorothioate oligonucleotide (dsODN) with sequence identical
      to the CYP1A1 negative regulatory element (NRE) was examined in Sprague-Dawley
      rats. Two strategies were employed: (i) two single-stranded complementary 25-mer
      ODNs that form a double-stranded ODN (ODN1) and (ii) a 54-base, self
      complementary ODN which forms a dsODN hairpin (ODN2). A dsODN hairpin with
      scrambled NRE sequence was evaluated as a control (ODN3). Zoxazolamine paralysis
      times, an in vivo marker of CYP1A1 activity, were reduced from 184 +/- 18 min in
      saline-treated rats to 103 +/- 12.5 min 24 hr after a single 1.7-mg ODN1 iv
      injection. Liver microsomal EROD, an in vitro marker of CYP1A1/2 activity, was
      increased from 210 +/- 10 pmol in saline-treated animals to 703 +/- 73 and 623 +/
      89 pmol resorufin/mg protein/min after iv ODN1 and iv ODN2, respectively. ODN1's
      activity did not change PNP hydroxylation and PROD, markers of CYPs 2E1 and
      2B1/2. ODN2 did not significantly change PNP but did significantly alter PROD.
      The ODN3 did not cause any significant changes in any assay measured. The ODN1
      induced responses in ZX paralysis and EROD were observed post-iv injection, but
      not following ip injection of ODN1. Western blot analysis of ODN1- and HPO
      treated rat liver microsomes also revealed increased in CYP1A1 protein. These
      data indicate double-stranded ODNs mimic the cis-acting NRE in vivo inducing
      CYP1A1 in the absence of other xenobiotics.

PMID- 8545826
TI  - Glutathione content and turnover in rat nasal epithelia.
AB  - During inhalation exposure to airborne toxicants, the nasal epithelium may be
      subjected to local toxicity. Since glutathione (GSH) is often involved in
      xenobiotic metabolism, GSH status in these tissues has been examined. GSH content
      and apparent first-order rate constants for GSH turnover and synthesis were
      determined for respiratory epithelium covering the anterior ventral septum and
      naso and maxillo turbinates, olfactory epithelium covering the dorsal posterior
      septum, and olfactory epithelium of the dorsal meatus from male Fischer-344 rats.
      The three tissues had GSH concentrations that ranged from 2.9 to 4.2 mumol/g
      tissue as determined by the Ellman's assay and by HPLC equipped with an
      electrochemical detector. Animals were administered [35S]cysteine (Cys) by tail
      vein injection and rate constants for GSH turnover were estimated, after
      incorporation of Cys into tissue GSH pools, by the decrease in GSH-specific
      activity 1-102 hr after administration. Total [35S]GSH was analyzed by HPLC with
      a flowthrough radioactivity detector. The respiratory epithelium had an apparent
      biphasic rate of GSH turnover, with a rapid-phase half-life of 4.4 hr and a slow
      phase half-life of 34 hr. The other epithelia had slower rates of GSH turnover,
      with half-lives greater than 30 hr. When half-lives of GSH turnover and GSH
      concentrations for nasal epithelia, and for 14 previously evaluated tissues, were
      compared it was found that tissues with high concentrations of GSH generally had
      a more rapid turnover of GSH than did tissues with low concentrations of GSH.
      However, apparent GSH turnover in the two regions of the olfactory epithelium
      poorly followed this trend.

PMID- 8545827
TI  - Dosing-induced stress causes hepatocyte apoptosis in rats primed by the rodent
      nongenotoxic hepatocarcinogen cyproterone acetate.
AB  - It has been proposed that several nongenotoxic compounds act as hepatocarcinogens
      by suppressing the apoptosis that would normally act to remove damaged or
      potentially initiated cells from the liver. During our investigations of this
      hypothesis using a widely applied protocol, we have found that the stress induced
      by the process of gavage dosing can induce massive apoptosis in livers uniquely
      primed by withdrawal of the hepatomitogen cyproterone acetate from the
      hyperplastic rat liver. This effect of gavage dosing was not seen in livers of
      naive animals. Apoptosis was measured by both in situ end labeling (ISEL) of the
      DNA damage associated with programmed cell death and conventional hematoxylin and
      eosin (H&E) staining of apoptotic morphology. Apoptotic rates measured by H&E
      increased significantly from 0.005 +/- 0.010% on Day 11 to 0.657 +/- 0.315% of
      hepatocytes on Day 15, 4 days after cessation of 10 days dosing with CPA (120
      mg/kg). The readministration of CPA suppressed > 89% of this Day 15 apoptosis.
      However, the readministration of vehicle alone (corn oil) caused a 390% increase
      in apoptosis to 2.56 +/- 1.31% of hepatocytes. Similar results were obtained
      using ISEL. Measurements of liver to body weight ratios and total DNA per liver
      reflected these changes in cell loss by apoptosis. In a second experiment, CPA
      was administered for 10 days as before then animals were subjected to
      readministration of CPA in corn oil, CPA in saline, corn oil, saline, or sham
      dosed. Again, apoptosis was dramatically suppressed by the readministration of
      CPA in either vehicle but was dramatically increased to around 2% of hepatocytes
      in all other groups, including the sham dosed group. Data on food consumption
      provided no evidence for a reduction in food intake as a causative agent but
      rather pointed to a less efficient usage of food in the stressed animals. The
      ability of stress to induce liver apoptosis should be borne in mind in the design
      and interpretation of future toxicological studies aimed at understanding the
      putative suppression of apoptosis by liver nongenotoxic carcinogens and other
      toxicants.

PMID- 8545828
TI  - The role of cytochrome P450 2E1 in the species-dependent biotransformation of 1,2
      dichloro-1,1,2-trifluoroethane in rats and mice.
AB  - 1,2-Dichloro-1,1,2-trifluoroethane (HCFC-123a) is a potential alternative to
      replace ozone-depleting chlorofluorocarbons. The metabolism of HCFC-123a was
      studied in microsomes of rats, mice, and humans as well as in rats and mice in
      vivo. Rat, mouse, and human liver microsomes metabolized HCFC-123a to inorganic
      fluoride and chlorodifluoroacetic acid. Fluoride formation was dependent on time
      and NADPH, HCFC-123a, and protein concentration. Microsomes from untreated rats
      oxidized HCFC-123a at low rates (0.49 nmol fluoride/20 min x mg protein).
      Pretreatment of rats with pyridine and ethanol, inducers of P450 2E1, increased
      the rates of fluoride release. In mouse liver microsomes, the rates of HCFC-123a
      oxidation to release fluoride were significantly higher (1.68 nmol fluoride/20
      min x mg) than in rat liver microsomes. Incubation of HCFC-123a with microsomes
      and diethyldithiocarbamate (100 microM), an inhibitor of P450 2E1, reduced
      fluoride formation by more than 60%. In different samples of human liver
      microsomes, rates of fluoride formation were between two- and fourfold higher
      than those observed in liver microsomes from untreated rats. In rats and mice
      exposed to concentrations of HCFC-123a up to 5000 ppm in a closed recirculating
      exposure system, chlorodifluoroacetic acid, and inorganic fluoride were
      identified as urinary metabolites. The biotransformation of HCFC-123a in rats was
      saturated after exposure to more than 2000 ppm HCFC-123a for 6 hr, whereas no
      saturation was evident in mice exposed to concentrations of up to 5000 ppm. The
      obtained results suggest a major role of P450 2E1 in the oxidation of HCFC-123a
      and in the different capacities for oxidative biotransformation of HCFC-123a in
      rodents. Mice may thus be more sensitive to toxic effects of HCFC-123a depending
      on biotransformation after administration of high doses.

PMID- 8545829
TI  - Aminoanthracene is a mechanism-based inactivator of CYP1A in channel catfish
      hepatic tissue.
AB  - In beta NF-induced channel catfish, hepatic ethoxyresorufin-O-deethylase (EROD)
      activity decreased 66.5% 24 hr after injection of 2-aminoanthracene (AA, 10
      mg/kg) compared with non-AA-injected animals (p < 0.05). This difference in
      hepatic EROD activity was also significant 48 hr after treatment (p < 0.05), but
      no significant difference was observed after 4 or 7 days. Immunoblot analysis of
      hepatic microsomal protein from fish 24 hr after treatment with AA revealed two
      bands cross-reacting with CYP1A-specific monoclonal antibody 1-12-3: an
      apparently native CYP1A protein (52 kDa) and a 30-kDa protein. Furthermore, these
      two proteins were preferentially bound by [3H]AA compared with other microsomal
      proteins. Interestingly, the 30-kDa protein was observed only in fish exposed to
      AA and was immunoprecipitable with 1-12-3. In a separate in vivo experiment,
      hepatic EROD activity decreased and the 30-kDa protein increased with increased
      dose of AA. The 30-kDa protein is thought to be a CYP1A degradation product. In
      vitro experiments helped elucidate the mechanisms of interaction between AA and
      CYP1A. Incubation of microsomes with AA, prior to analysis of these microsomes
      for EROD activity, resulted in a NADPH- and time-dependent inhibition of EROD
      activity. Additionally, the P450 inhibitors 1-phenylimidazole and 3,3',4,4'
      tetrachlorobiphenyl were used to decrease the binding of AA to CYP1A, suggesting
      that the binding of AA to CYP1A requires the enzymatic activity of CYP1A. It is
      proposed that mechanism-based inactivation of CYP1A by AA accounts for the
      observed AA-dependent decrease in hepatic EROD activity in vitro and in vivo in
      channel catfish.

PMID- 8545830
TI  - The effect of cadmium chloride in vitro on sodium-glutamate cotransport in brush
      border membrane vesicles isolated from rabbit kidney.
AB  - To further elucidate the mechanism of cadmium inhibition of renal amino acid
      transport, brush border membrane vesicles were isolated from rabbit renal cortex
      and the effect of cadmium on the uptake of L-glutamate into the vesicles was
      investigated. Preincubation of the membranes with CdCl2 decreased sodium
      dependent L-glutamate uptake at concentrations higher than 10(-6)M. In the
      presence of 20 mM potassium inside the vesicles a half-maximal inhibition was
      observed at 0.5 to 1 x 10(-4) M. Kinetic analysis revealed a strong reduction of
      Vmax by cadmium but only minor changes in Km for glutamate. The inhibition
      required preincubation of the vesicles with cadmium, was not elicited by cadmium
      metallothionein, and was not reversed by ethylenediaminetetraacetic acid. These
      findings suggest an action of cadmium at the cytoplasmic face of the brush border
      membrane. Furthermore, the sensitivity of the transport system for cadmium was
      lower in the absence of potassium. Inhibition increased in a saturable manner
      when intravesicular potassium was augmented, indicating that the transporter
      interacts with cadmium most avidly when potassium is bound to the carrier.

PMID- 8545831
TI  - Transgenic mice that overexpress metallothionein-I are protected from cadmium
      lethality and hepatotoxicity.
AB  - The purpose of this study was to determine whether metallothionein-I (MT-I)
      transgenic female mice (MT-TG) are resistant to cadmium (Cd) hepatotoxicity.
      Female MT-TG mice have 10- to 20-fold higher MT concentrations in liver than
      control mice and are more resistant to Cd-induced lethality than control mice.
      CdCl2 (3.7 mg Cd/kg, iv) was lethal to 73% of control mice, but only to 13% of MT
      TG mice. Cd administration (3.1 mg/kg, iv) to control mice produced extensive
      liver injury as evidenced by 20- and 70-fold increases in serum enzyme activities
      of sorbitol dehydrogenase and alanine aminotransferase, respectively. MT-TG mice
      are considerably more resistant to Cd-induced hepatotoxicity than control mice,
      as evidenced by only about one-tenth the elevation in serum enzymes observed in
      control mice and a lower incidence of hepatocyte necrosis in MT-TG mice. To
      ascertain the mechanism of this protection, the distribution of Cd to various
      organs and the subcellular distribution of Cd in liver were determined 2 hr after
      Cd injection (109CdCl2, 3.5 mg Cd/kg, iv). The hepatic subcellular distribution
      of Cd was altered markedly in MT-TG mice, with much less Cd distributing to
      nuclei, mitochondria, and microsomes (25, 42, and 24% of controls, respectively),
      and more Cd to the cytosol (240% of controls). The increased cytosolic Cd was
      bound primarily to MT, as determined by G-75 gel chromatography. In addition,
      primary hepatocyte cultures from MT-TG mice maintained higher levels of MT than
      hepatocytes from control mice and were more resistant to Cd cytotoxicity than
      control hepatocytes. In conclusion, studies using MT-I transgenic mice
      demonstrate that MT protects against Cd lethality and hepatotoxicity, and this
      hepatoprotective effect of MT is also observed in hepatocyte cultures from MT-TG
      mice.

PMID- 8545832
TI  - Effect of the hepatocarcinogenic peroxisome proliferator Wy-14,643 in vivo: no
      increase in ethane exhalation or hepatic conjugated dienes.
AB  - Exhalation of ethane and pentane was used to access lipid peroxidation in rats
      receiving the hepatocarcinogenic peroxisome proliferator Wy-14,643 at 0.1% in the
      diet. Wy-14,643 treatment from 23 to 345 days did not increase ethane or pentane
      exhalation. The lack of an increase in ethane exhalation from rats fed Wy-14,643
      was not due to resistance to lipid peroxidation or increased metabolism of ethane
      since rats fed Wy-14,643 were sensitive to CCl4-induced increases in ethane
      exhalation and cleared exogenous ethane at rates similar to controls. Difference
      spectra of hepatic lipids extracted from control and Wy-14,643-treated rats
      showed peaks at 220 and 275 nm but no defined peak at 240 nm, the wavelength at
      which conjugated dienes in peroxidized lipids absorb. In contrast, injection of
      CCl4 ip into control rats produced dose-dependent increases in ethane exhalation
      at 6.25 to 100 microliters/kg and increases in hepatic conjugated dienes and
      serum liver enzyme activities at 200 to 1000 microliters/kg. The lack of
      increased ethane and pentane exhalation in combination with no detectable
      increase in hepatic conjugated dienes argues against increased hepatic lipid
      peroxidation in rats receiving a hepatocarcinogenic dose of Wy-14,643.

PMID- 8545833
TI  - Real time microfiberoptic redox fluorometry: modulation of the pyridine
      nucleotide status of the organogenesis-stage rat visceral yolk sac with cyanide
      and alloxan.
AB  - The surface of rat visceral yolk sacs (VYS) of intact, viable rat conceptuses
      were continuously monitored with a microfiberoptic sensor optimized for detection
      of the reduced pyridine nucleotides, NADH and NADPH. Model chemical toxins,
      cyanide and alloxan, were used and evaluated on the basis of their differential
      ability to modulate NAD(H)- and NADP(H)-dependent cellular pathways,
      respectively. Exposure with 2 mM sodium cyanide for 5 min caused a reversible
      fluorescence increase of 325 arbitrary fluorescence units (AFU) and 225 AFU on
      Gestational Days (GD) 10 and 11, respectively. Exposure with 40 mM alloxan for 5
      min resulted in a fluorescence decrease of 170 and 120 AFU on GD 10 and 11,
      respectively. Glutathione (GSH) levels in the VYS, as determined by HPLC, showed
      a marked decrease from 27.3 +/- 2.1 to 2.9 +/- 0.4 pmol/mg protein, within the 5
      min alloxan exposure period on GD 10. No decrease in GSH levels was noted for the
      same exposure duration on GD 11. A 2-hr pretreatment with 25 microM BCNU [(1,3
      bis(2-chloroethyl)-1-nitrosourea], to inhibit glutathione disulfide reductase
      (GSSG-Rd), resulted in an elimination of the fluorescence decrease, but still led
      to a significant drop in GSH levels as seen on both days of gestation. These
      results are consistent with overall changes in intracellular pyridine nucleotide
      concentrations, where the relative amounts of NADPH increase significantly and
      disproportionately from GD 10 to 11. The net oxidation of NADPH, through GSSG-Rd
      activity, appears to be responsible for the alloxan-induced decrease in surface
      fluorescence. Conversely, the cyanide-induced fluorescence increases appear to be
      the result of NAD+ reduction, mediated through the inhibition of the terminal
      cytochrome oxidase in the electron transport chain.

PMID- 8545834
TI  - Postnatal development of cytochrome P4501A1 and 2B1 in rat lung and liver: effect
      of aged and diluted sidestream cigarette smoke.
AB  - Earlier studies have shown that both mainstream and sidestream cigarette smoke
      increase the activities of cytochrome P4501A1 and 2E1 in the lungs of adult
      animals; however, little information is available on the influence of ambient
      levels of sidestream cigarette smoke on cytochrome P450 monooxygenase activity in
      the developing lung. The present studies were conducted to define the
      developmental profiles of cytochrome P450 monooxygenases 1A1 and 2B1 in rat lung
      and liver and to assess the effects of aged and diluted sidestream cigarette
      smoke (ADSS) on the developmental profile of these two enzymes. Accordingly,
      pulmonary and hepatic microsomal P4501A1 and 2B1 activities were determined by
      measuring ethoxy- and pentoxyresorufin-O-delakylase (EROD and PROD, respectively)
      activity in animals exposed to filtered air or ADSS from birth to 7, 14, 21, 50,
      and 100 days of age. Pulmonary P4501A1 activity in control rats was not detected
      until 14 days of age. Activities increased threefold between 14 and 21 days of
      age and remained unchanged to 100 days of age. In animals exposed to ADSS from
      birth, pulmonary EROD activities were detected as early as 7 days postnatal and
      were elevated three- to fourfold above control at all other ages examined.
      Hepatic EROD activities were unaltered by ADSS exposure. Short-term (4-day) ADSS
      exposure was as effective in upregulating pulmonary microsomal EROD activities as
      100-day exposures. Induction of pulmonary EROD activities and the associated
      increases in mRNA levels were dependent upon the particulate fraction.
      Stimulation of EROD activities in major and minor daughter subcompartments was
      three- to fourfold higher in ADSS-exposed animals compared to controls, while
      there was no induction in the trachea and less than a twofold increase in the
      parenchyma. Pulmonary PROD activities developed more slowly than EROD and did not
      reach adult levels until Day 50. ADSS did not alter pulmonary or hepatic PROD
      activities. These studies show that P4501A1 and 2B1 develop at different rates in
      rat lung and liver and that exposure to ADSS markedly increases P4501A1
      activities in the lung at all ages examined.

PMID- 8545835
TI  - Sustained stimulation of rat adrenal chromaffin cell proliferation by reserpine.
AB  - Chronic administration of reserpine is associated with the development of
      pheochromocytomas in rats. Short-term administration of reserpine to rats has
      been shown to stimulate chromaffin cell proliferation, leading to the hypothesis
      that reserpine causes pheochromocytomas indirectly by providing a proliferative
      backdrop on which genetic damage may occur. However, it is not known whether the
      proliferative effects of reserpine persist long enough for this model to be
      tenable. In the present investigation, the effects of reserpine on
      bromodeoxyuridine (BrdU) incorporation into epinephrine (E)- and norepinephrine
      (NE)-type chromaffin cells were studied after 1, 4, and 12 weeks of reserpine
      administration. Reserpine administered in the diet at 10 or 50 ppm was shown to
      result in a persistent mitogenic stimulation of the rat adrenal medulla. Cells
      that incorporated BrdU at all time points appeared to be typical E- and NE-type
      chromaffin cells, and the ratio of BrdU-labeled E cells to BrdU-labeled NE cells
      was not altered by reserpine. An additional observation was that the ratio of all
      E cells to all NE cells declined after Week 1 and that the decline could be
      accelerated by administration of reserpine. This finding suggests that neural
      stimulation of chromaffin cells might play a role in age-related functional
      changes of the adrenal medulla during early adult life. The present observations
      support the hypothesis that reserpine induces pheochromocytomas indirectly by
      increasing chromaffin cell proliferation. They also decrease the likelihood that
      rat pheochromocytomas arise from preferential stimulation of proliferation of a
      particular cell type.

PMID- 8545836
TI  - Neuropeptide modulation of chemically induced skin irritation.
AB  - This study addresses the hypothesis that the early symptoms of chemically induced
      skin irritation are neurally mediated. Several approaches were used to affect
      nerve transmission in adult Balb/c female mice. These included general anesthesia
      (i.e., sodium pentobarbital), systemic capsaicin treatment, and pretreatment with
      specific pharmacological antagonists of the neuropeptides substance P (SP) and
      neurokinin A (NKA). After these treatments, a strongly irritating dose of
      dinitrofluorobenzene (DNFB) was applied to the ear and its swelling was measured
      over several postexposure times as an index of tissue irritation. Ear swelling in
      Nembutal (30 mg/kg)-anesthetized mice was depressed 62 and 76% at 4 and 24 hr
      postexposure compared to DNFB-treated unanesthetized animals measured at the same
      time points. Multiple injections of capsaicin (cumulative dose 30 mg/kg)
      depressed DNFB-ear swelling relative to non-capsaicin, DNFB-treated controls by
      15, 40 (ip), and 44 and 43% (sc) at 4 and 24 hr postexposure, respectively. In
      mice exposed to acute or multiple injections of the SP antagonist CP-96,345
      before DNFB application, ear swelling was depressed (relative to DNFB-treated
      animals) by 64 and 36% (acute, sc, 10 mg/kg) and 91 and 88% (multiple, ip,
      cumulative 35 mg/kg) at 0.5 and 1 hr postexposure, respectively. Mice exposed to
      the NKA antagonist, SR 48968, alone and in combination with the SP antagonist CP
      96,345 were also examined after DNFB application. Ear swelling was diminished in
      mice pretreated with the NKA antagonist (1.0 mg/kg) by 17, 24, 34, and 40% at
      0.5, 1, 4, and 24 hr postexposure. When used in combination with the SP
      antagonist, DNFB-induced ear swelling was reduced by 95% compared to
      unantagonized, DNFB-exposed mice at the 0.5- and 1-hr time points and remained
      significantly depressed by 33 and 46% at 4 and 24 hr postexposure. Taken in
      concert, these data suggest that neuropeptides, especially the tachykinins SP and
      NKA, modulate the early stages of chemically induced skin irritation.

PMID- 8545837
TI  - Effects of nicotine on the immune response. I. Chronic exposure to nicotine
      impairs antigen receptor-mediated signal transduction in lymphocytes.
AB  - Previous work has demonstrated that chronic exposure of rats to cigarette smoke
      causes inhibition of the antibody-forming cell (AFC) response and that the
      particulate phase of cigarette smoke, containing most of the nicotine in
      cigarette smoke, is essential for immunosuppression. Using intradermally
      implanted miniosmotic pumps, LEW rats were exposed to nicotine or its principal
      metabolite, cotinine, at the rate of about 14 micrograms/hr for 3-4 weeks. Serum
      cotinine levels in nicotine-treated (NT) animals of 219 +/- 40 ng/ml (on Day 10)
      were comparable to average human smokers. No significant differences between
      control (CON) and NT animals were observed in the distribution of lymphocyte
      subsets. However, nicotine, but not cotinine, treatment for 3 to 4 weeks
      inhibited both the T-dependent and T-independent AFC responses and proliferation
      to anti-CD3. Con A response was observed in 4-week but not in 3-week NT animals.
      Cell cycle analysis revealed that upon stimulation with Con A or anti-CD3, in
      spite of comparable surface expression of IL-2 receptors and class II MHC
      molecules, significantly fewer NT T cells entered the S and G2/M phases than CON
      T cells, indicating an arrest in the G0/G1 phase. Furthermore, B and T cells from
      NT animals were unable to elevate the intracellular calcium levels normally in
      response to ligation of antigen receptors, although Ca2+ responses of salivary
      gland cells to acetylcholine were normal. Thus, nicotine may significantly
      contribute to the immunosuppressive effects of chronic smoking by inducing a
      state of anergy in lymphocytes and may be related to their impaired response to
      antigen-induced signaling.

PMID- 8545838
TI  - Extent and persistence of streptozotocin-induced DNA damage and cell
      proliferation in rat kidney as determined by in vivo alkaline elution and BrdUrd
      labeling assays.
AB  - The extent of DNA damage and cellular proliferation induced in rat kidneys by
      single doses of the diabetogenic alkylating agent streptozotocin (STZ) and the
      time course of repair of that damage were evaluated using an in vivo alkaline
      elution assay for DNA strand breaks and a bromodeoxyuridine (BrdUrd) labeling
      assay for cell replication. Male Sprague-Dawley rats were given iv injections of
      0.25 to 60 mg/kg STZ and kidneys were harvested 3 hr later for alkaline elution.
      A dose of 2.5 mg/kg STZ was the lowest dose to induce detectable DNA strand
      breaks and extensive damage was produced by the commonly used diabetogenic dose
      of 60 mg/kg. To characterize the repair of the drug-induced DNA damage, kidneys
      were harvested from a 60 mg/kg group of animals 3 hr to 27 days after dosing.
      BrdUrd-labeled kidney sections were also evaluated to assess any cellular
      proliferative response associated with STZ administration. Significant DNA damage
      was detected up to 14 days after dosing with return to near background levels by
      20 days. Similarly, treatment with 60 mg/kg STZ was associated with increases in
      BrdUrd labeling indices 4 and 9 days after treatment with resolution by 27 days.
      These results indicate that the cellular and molecular repair responses to a
      single diabetogenic dose of STZ are prolonged, requiring up to 3 weeks to
      complete. Thus, to avoid potential additive or synergistic effects on STZ-induced
      nephrotoxicity and/or genotoxicity, a delay in the start of experimental
      therapies in this model (other than insulin) should be considered.

PMID- 8545839
TI  - Alkyl polychlorinated dibenzofurans and related compounds as antiestrogens in the
      female rat uterus: structure-activity studies.
AB  - The antiestrogenic activity of a series of alkyl-substituted polychlorinated
      dibenzofurans (PCDFs) were determined in the immature female Sprague-Dawley rat
      uterus. The compounds utilized in this study contain two, three, or four lateral
      substitutents and include: 6-methyl-1,3,8-triCDF, 6-ethyl-1,3,8-triCDF, 6-n
      propyl-1,3,8-triCDF, 6-i-propyl-1,3,8-triCDF, 6-t-butyl-1,3,8-triCDF, 8-methyl
      1,3,6-triCDF (two lateral substituents); 6-methyl-2,3,8-triCDF, 6-methyl-2,3,4,8
      tetraCDF, 8-methyl-1,3,7-triCDF, and 8-methyl-1,2,4,7-tetraCDF (three lateral
      substituents); 8-methyl-2,3,7-triCDF, 8-methyl-2,3,4,7-tetraCDF (four lateral
      substituents). Two additional compounds, 8-methyl-2,3,7-trichlorodibenzo-p-dioxin
      and 8-methyl-2,3,7-tribromodibenzo-p- dioxin (four lateral substituents), were
      also utilized. All of the alkyl-substituted compounds inhibited estrogen-induced
      uterine wet weight increase and cytosolic and nuclear progesterone and estrogen
      receptor binding. The effects of structure on the antiestrogenic potencies were
      determined using 6-i-propyl-1,3,8-triCDF, 6-methyl-2,3,4,8-tetraCDF, and 8-methyl
      2,3,4,7-tetraCDF as representative congeners containing two, three, and four
      lateral substituents, respectively. The ED50 values for antiestrogenicity were
      similar for the three compounds; however, the ED50 values for induction of
      hepatic CYP1A1-dependent activity were 73,600 (estimated), 8.52, and 5.31
      mumol/kg for 6-i-propyl-1,3,8-triCDF, 6-methyl-2,3,4,8-tetraCDF, and 8-methyl
      2,3,4,7-tetraCDF, respectively. Since CYP1A1 can be used as a surrogate for toxic
      potency in the rat then high ED50 (induction)/ED50 (antiestrogenicity) ratios
      would be indicative of low toxicity and high antiestrogenic potency. The ratio
      was 13,990 to 17,100 for 6-i-propyl-1,3,8-triCDF, whereas the corresponding value
      for the compounds with three or four lateral substituents varied from 0.64 to
      3.34. The results suggests that the 1,3,6,8-substituted alkyl PCDFs are useful
      structural models for developing new aryl hydrocarbon receptor-mediated
      antiestrogens for future clinical use as antiestrogens.

PMID- 8545840
TI  - Nifedipine and tetrodotoxin delay the onset of methylmercury-induced increase in
      [Ca2+]i in NG108-15 cells.
AB  - Methylmercury (MeHg) causes a multiphasic disruption of intraneuronal cation
      regulation. Release of Ca2+ from internal stores and entry of extracellular Ca2+
      (Ca2+e) contribute to the temporally distinct early (first Ca2+ phase) and late
      (second Ca2+ phase) components of increased intracellular Ca2+ concentration
      ([Ca2+]i). The present study was designed to explore the mechanisms mediating the
      second Ca2+ phase. Fluorescence intensity was monitored from single NG108-15
      cells loaded with fura-2 before and during acute application of 2 microM MeHg.
      Nifedipine (1 or 10 microM but not 0.1 microM) significantly delayed the time-to
      onset of the second Ca2+ phase. Nifedipine (1 microM but not 0.1 microM) also
      caused a concentration-dependent delay in the onset of both the first Ca2+ phase
      which is independent of Ca2+e and the elevation of non-Ca2+ cation (non-Ca2+
      phase). The L-type dihydropyridine (DHP) Ca2+ channel agonist Bay K-8644 (10 nM)
      had no effect on the time-to-onset of the second Ca2+ phase. Neither the N-type
      Ca2+ channel blocker omega-conotoxin GVIA (up to 1 microM) nor the nonselective
      Ca2+ channel blocker Ni2+ (1 mM) altered the time-to-onset of the second Ca2+
      phase. Removal of Na+e or addition of the voltage-dependent Na+ channel
      antagonist tetrodotoxin (TTX, 1 microM) significantly delayed the onset of the
      second Ca2+ phase. In a manner similar to that for 1 microM nifedipine, TTX also
      delayed the onset of the other phases. Thus, we hypothesize that MeHg depolarizes
      the plasma membrane leading to an increase in the activation of voltage-dependent
      Na+ and Ca2+ channels which promotes, directly or indirectly, the influx of Ca2+
      during the second Ca2+ phase.

PMID- 8545841
TI  - Tissue-specific effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on the
      activity of phosphoenolpyruvate carboxykinase (PEPCK) in rats.
AB  - Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in
      liver, together with feed refusal, has been suggested to play an important role
      in TCDD-induced lethality in rats. In this study the toxicological significance
      of reduced gluconeogenesis was further analyzed by studying dose responses and
      time courses of effects of TCDD on the activity of PEPCK in liver and two other
      tissues with high specific activity, viz. kidney and brown adipose tissue (BAT).
      Liver PEPCK activity was significantly decreased from 1 to 32 days after dosing
      (60 micrograms/kg). A clear dose response was present 8 days after dosing,
      beginning at a dose of 1 microgram/kg. In contrast to liver, TCDD treatment
      increased PEPCK activity in kidney and BAT, but only at the two highest doses
      administered (30 and 60 micrograms/kg). PEPCK activity in kidney began to
      increase slowly, reaching a maximum on Day 16 and declining thereafter, whereas
      in BAT the activity was significantly increased already on Day 1 and maximally on
      Day 4 after dosing. A likely explanation for these tissue-specific effects is in
      part related to toxicokinetics and in part to homeostatic responses of the
      organism to the toxic insult of TCDD. High concentrations of TCDD in liver and
      BAT combined with early responses (1 day after dosing) suggest a direct effect in
      these organs/tissues, whereas very low concentration and delayed response in
      kidney indicate an indirect effect. This interesting enzymatic constellation
      suggests that the reduction in gluconeogenesis due to decreased PEPCK activity in
      liver is partially counterbalanced by increased gluconeogenesis in kidney as a
      result of induction of PEPCK in this organ. Induction of PEPCK in BAT, where it
      is a glyceroneogenic enzyme, provides for the first time a plausible explanation
      for the initial accumulation of fat in BAT of TCDD-treated rats.

PMID- 8545842
TI  - An attempt to explain interindividual variability in 24-h urinary excretion of
      inorganic arsenic metabolites by C57 BL/6J mice.
AB  - Forty C57 BL/6J mice, injected subcutaneously with 0.5 mg/kg arsenic as sodium
      arsenite, were examined for 24-h urinary excretion of total arsenic metabolites,
      creatinine and S-adenosylmethionine (SAM) and for 24-h faecal excretion of
      arsenic and levels of arsenic in the blood, liver, kidneys, lung, skin, spleen
      and bone at 24-h post-dose. Total urinary arsenic metabolites were calculated by
      summing up the inorganic (Asi), monomethylated (MMA) and dimethylated (DMA)
      derivatives directly measured by selective arsine generation-atomic absorption
      spectrometry (AG-AAS) or were measured by AG-AAS following complete
      mineralization. Both sets of results showed interindividual differences varying
      by as much as 7-fold and correlated with the 24-h urinary excretion of both SAM
      (r = 0.84 and r = 0.86, respectively) and creatinine (r = 0.82 and r = 0.87,
      respectively). There was interindividual variability of about a 30-fold range in
      24-h faecal excretion of arsenic which correlated inversely with 24-h urinary
      excretion of arsenic metabolites (r = -0.69) and 24-h urinary excretion of both
      creatinine (r = -0.70) and SAM (r = -0.67). Body tissue levels of arsenic were
      low and not related to 24-h urinary excretion of arsenic metabolites, SAM and
      creatinine. Taken together, the results indicate that differences in the profile
      of urinary arsenic excretion and in the retention of arsenic in a particular
      organ do not contribute to interindividual variability in 24-h urinary excretion
      of arsenic metabolites by C57 BL/6J mice, but that variability in faecal
      excretion does, at least in part. It is speculated that there is most likely a
      predominant contribution from a diffuse tissue retention of arsenic or from a
      third route of arsenic elimination, i.e. respiratory, to this phenomenon in view
      of the small faecal contribution.

PMID- 8545843
TI  - Cell injury and protection in long-term incubation of liver slices after in vivo
      initiation with paracetamol: cell injury after in vivo initiation with
      paracetamol.
AB  - Short-term in vitro methods (2-6 h) for study of cell injury by paracetamol are
      often used but, in vivo, injury is not apparent until 12 h or later. Many agents
      which protect in the short-term in vitro systems, such as fructose and glycerol
      which are effective, even in the late phase, after paracetamol has initiated
      injury, do not provide any protection in vivo. We have extended the in vitro
      liver slice system to a more realistic 18 h. Secondly, we have initiated injury
      with paracetamol in vivo, then followed the progression of injury in an in vitro
      system. Control liver slices incubated in a HEPES Ringer solution with
      antibiotics over 18 h show little sign of injury as demonstrated by leakage of
      lactate dehydrogenase (LDH) into the medium or loss of potassium. Liver slices
      exposed to 10 mM paracetamol for 2 h in vitro show extensive LDH leak at 6 h
      which is even more severe at 18 h. Liver slices from animals treated with
      paracetamol (1 g/kg i.p.) in vivo for 3 h show little LDH leakage at 6 h in vitro
      but by 18 h injury is very apparent. Fructose and glycerol which protect against
      paracetamol injury in the short-term (6-h) in vitro system, do not do so when
      observations are extended to 18 h. They also fail to provide any protection to
      the slice from animals pre-treated in vivo with paracetamol. Other agents show
      similar affects. There is no convincing evidence that these short-term protective
      agents afford any protection in vivo and we show that ibuprofen and dexamethasone
      do not protect in vivo. It is clear that short-term assays for cell protection
      have only a limited explanatory value.

PMID- 8545844
TI  - Effects of bolesatine on a cell line from the SP2/O thymic lymphosarcoma.
AB  - Bolesatine, a toxic protein isolated from Boletus satanas Lenz inhibits in vitro
      protein synthesis in a concentration-dependent manner in a cell line from a
      radiation-induced thymic lymphosarcoma (SP2/O) with a 50% inhibitory
      concentration (IC50) of 9.5 nM (0.6 microgram/ml). In vivo, an i.p. single
      injection of bolesatine, corresponding to 1/6 and 1/10 of 24-h 50% lethal dose,
      in Balb/c mice having ascitic tumour induced by the i.p. preinjection of SP2/O
      cells allows a remission of 50% and 30%, respectively. Treated mice survived 120
      days after the treatment, i.e. 90 days after the death of control animals.

PMID- 8545845
TI  - Structure-activity relationships of organic acid anhydrides as antigens in an
      animal model.
AB  - Relationships between chemical structure and immunogenicity have been studied in
      13 dicarboxylic acid anhydrides. Guinea-pigs were immunized intradermally by a
      single dose of 0.3 M solutions of succinic anhydride (SA), maleic anhydride (MA),
      methylmaleic anhydride (MMA), cis-cyclohexane-1,2-dicarboxylic anhydride (cis
      HHPA), trans-cyclohexane-1,2-dicarboxylic anhydride (trans-HHPA), 4
      methylcyclohexane-1,2-dicarboxylic anhydride (MHHPA), cis-1,2,3,6
      tetrahydrophthalic anhydride (THPA1236), cis-3,4,5,6-tetrahydrophthalic anhydride
      (THPA3456), cis-3-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA34), cis
      4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA44), phthalic anhydride
      (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive
      oil. Specific IgE, IgG, IgG1, and IgG2 antibodies against guinea-pig serum
      albumin conjugates of the anhydrides were determined by passive cutaneous
      anaphylaxis (PCA) tests and enzyme-linked immunoabsorbant assay (ELISA). Specific
      IgG was significantly increased in all animals, except those immunized with
      THPA3456 and SA, which sensitized only 3/9 and 7/9 animals, respectively.
      Furthermore, the specific IgG values were very low in the SA group. The titers of
      specific IgG1 and IgG2 were increased in the IgG-positive animals. Specific IgE
      was positive in all animals immunized with MA, MHHPA, MTHPA (both isomers), and
      MPA, and in 6/9 and 5/9 guinea pigs immunized with TMA and MMA, respectively. The
      IgE titers were generally very low; PCA was negative after dilutions to 1:32, or
      less. The results indicate a considerable variation in the sensitizing potential
      between different organic acid anhydrides. The most marked general effect of the
      chemical structure on immunogenicity was the enhancement of antibody formation
      when a hydrogen atom in the anhydride was substituted with a methyl group.

PMID- 8545846
TI  - Hazardous substances data bank (HSDB) as a source of environmental fate
      information on chemicals.
AB  - The Hazardous Substances Data Bank (HSDB), a factual data bank on the National
      Library of Medicine's (NLM) TOXNET (Toxicology Data Network) online system,
      provides information in areas such as chemical substance identification, chemical
      and physical properties, safety and handling, toxicology, pharmacology,
      environmental fate and transformation, regulations, and analytical methodology.
      This article discusses how environmental fate data is handled in HSDB.

PMID- 8545847
TI  - Experimental studies on the long-term effects of methylphenidate hydrochloride.
AB  - Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug
      used in the treatment of attention-deficient disorders, were performed in F344
      rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was
      administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats
      and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50
      animals/dose/sex/species. The average amount of methylphenidate consumed per day
      was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival
      was similar in dosed and control groups. An increase in benign tumors of the
      liver and increased liver weights were observed in male and female mice at the
      high dose. An increase in hepatoblastomas was also seen in high dose male mice.
      Methylphenidate was not mutagenic in the Salmonella assay system, and it is
      hypothesized that this tumorigenic effect might be due to nongenotoxic effects of
      the chemical such as an increase in cell proliferation. Increased incidences of
      neoplasms were not seen in rats. However, there was a notable decrease in mammary
      gland fibroadenomas in female rats and a marginal decrease in benign
      pheochromocytomas in male rats. Epidemiology studies of methylphenidate have
      found no evidence of a carcinogenic effect in humans and like our findings in
      rats, report a less than expected rate of cancers in patients taking
      methylphenidate.

PMID- 8545848
TI  - Susceptibility of primary cultures of proximal tubular and distal tubular cells
      from rat kidney to chemically induced toxicity.
AB  - Isolated proximal tubular (PT) and distal tubular (DT) cells from rat kidney were
      cultured for up to 9 days under serum-free, hormonally-defined conditions on 35
      mm polystyrene culture dishes. Several hormonal and growth factor supplements
      were assessed for their ability to promote growth (increased protein and DNA
      content) and stability of differentiated phenotype (high activities of gamma
      glutamyltransferase and alkaline phosphatase as brush-border membrane markers in
      PT cells; maintenance of high activities of glutamate dehydrogenase as a
      mitochondrial marker in both PT and DT cells; maintenance of low and high
      activities of lactate dehydrogenase in PT and DT cells, respectively; expression
      of cytokeratins). Basal supplemented media (DMEM/F12, 1:1 v/v) contained insulin,
      hydrocortisone, epidermal growth factor, sodium selenite and transferrin as
      supplements. Additionally, triiodothyronine selectively promoted growth and
      stability of differentiated phenotype in PT cells and thyrocalcitonin selectively
      promoted growth and stability of differentiated phenotype in DT cells. On Day 3
      of primary culture, PT and DT cells were incubated for up to 8 h with either tert
      butyl hydroperoxide (tBH; 0.5-10 mM), methyl vinyl ketone (MVK; 1-10 mM), or p
      aminophenol (PAP; 1-10 mM) and cellular injury, as assessed by cellular release
      of lactate dehydrogenase, was determined. DT cells were significantly more
      susceptible to injury from both tBH and MVK, but the two cell populations were
      equally susceptible to injury from PAP, which is the same susceptibility pattern
      seen in freshly isolated cells. These results suggest that primary cultures of
      rat renal PT and DT cells reflect similar biochemical properties as freshly
      isolated cells and are, therefore, useful models for study of chemically induced
      injury.

PMID- 8545849
TI  - An unusual rearrangement product formed during production of mometasone furoate
      (Sch 32088).
AB  - The structure of an unusual rearrangement product obtained during the production
      of mometasone furoate (Sch 32088) was assigned on the basis of NMR and X-ray
      crystallography data.

PMID- 8545850
TI  - Radioimmunoassay of three deoxycorticoids in human plasma following HPLC
      separation.
AB  - A radioimmunoassay of three deoxycorticoids, namely 11 beta,17 alpha-dihydroxy-4
      pregnene-3,20-dione (21-deoxycortisol), 17 alpha,21-dihydroxy-4-pregnene-3,20
      dione (11-deoxycortisol), and 21-hydroxy-4-pregnene-3,20-dione (11
      deoxycorticosterone) which are important for differential diagnosis of congenital
      adrenal disorders, is described and evaluated. Antisera against 3-(O
      carboxymethyl)oximes conjugated to bovine serum albumin were raised in rabbits.
      The radioligands were prepared by radioiodination of previously synthesized
      homologous tyrosine methyl ester derivatives. Following diethyl ether extraction,
      the steroids were separated from each other and from cross-reactants by HPLC
      using a Nucleosil C8 reverse-phase column and a methanol-water mixture (7:5, v/v)
      as an eluent. Normal levels of analyzed steroids ranged from 0.02 to 0.348, 0.185
      to 3.80, and 0.013 to 0.299 nmol/l, for 21-deoxycortisol, 11-deoxycortisol and 11
      deoxycorticosterone, respectively. The levels of both deoxycortisols rose
      significantly after ACTH treatment. Data are given with respect to the
      concentrations of these steroids in some pathological situations such as 21
      hydroxylase and 11 beta-hydroxylase block, hyperaldosteronism, and polycystic
      ovary syndrome.

PMID- 8545851
TI  - Microbial transformation of beta-sitosterol and stigmasterol into 26-oxygenated
      derivatives.
AB  - The genetically modified Mycobacterium sp. BCS 396 strain has been used to
      transform sterols with stigmastane side chain in order to obtain 26-oxidized
      metabolites. beta-Sitosterol (I) was transformed to 4-stigmasten-3-one (II), 26
      hydroxy-4-stigmasten-3-one (III), and 3-oxo-4-stigmasten-26-oic acid (IV), while
      stigmasterol (V) was converted to 4,22-stigmastadien-3-one (VI), 6 beta-hydroxy
      4,22-stigmastadien-3-one (VII), 26-hydroxy-4,22-stigmastadien-3-one (VIII), 3-oxo
      4,22-stigmastadien-26-oic acid methyl ester (IX), and 3-oxo-1,4,22-stigmastatrien
      26-oic acid methyl ester (X) with that strain. In both beta-sitosterol and
      stigmasterol, 26-oxidation generates the R-configuration on C-25.

PMID- 8545852
TI  - Novel 26-oxygenated products in microbial degradation of ergosterol.
AB  - In order to investigate the effect of the different stereochemistry of C-24 on
      the microbial C-26 oxidation of sterol side-chain the genetically modified
      Mycobacterium sp. BCS 396 strain was used to transform erogsterol. Ergosterol was
      converted to 3-oxo-4,22-ergostadien-26-oic acid methyl ester, 3-oxo-1,4,22
      ergostatrien-26-oic acid methyl ester, and 3-oxo-1,4,22-ergostatrien-26-oic acid,
      the structures of which have been determined by IR, 1H NMR, 13C NMR, and mass
      spectroscopy. The X-ray structure of 3-oxo-4,22-ergostadien-26-oic acid methyl
      ester revealed that oxidation at C-26 of the ergostane side-chain generates a
      chiral center with S-configuration at C-25 as a result of chiral induction of the
      C-24 center.

PMID- 8545853
TI  - Molecular interactions of levonorgestrel and its 5 alpha-reduced derivative with
      androgen receptors in hamster flanking organs.
AB  - The 5 alpha-reduction of levonorgestrel (LNG) as well as its binding capacity to
      the androgen receptors of the hamster flank organ were investigated. Furthermore,
      the effects of LNG and its 5 alpha-reduced metabolite in the flank organ test and
      on [U-14C]glucose incorporation into lipids by this tissue were determined.
      Homogenates from female hamster flank organs were incubated in the presence of
      [3H]LNG at pH 7.4. The radioactive 5 alpha-LNG metabolite was isolated and its
      purity was assessed. Competition experiments for androgen binding receptors were
      carried out with 1.38 nM [3H-7 alpha-17 alpha]dimethyl-19- nortestosterone
      (DMNT), Kd, plus a range of increasing concentrations of the different unlabeled
      steroid hormones. The flank organ test was performed in vivo, and [U-14C]glucose
      incorporation into lipids was determined under organ culture conditions. The 5
      alpha-LNG had the same binding capacity to androgen receptors (AR) as LNG in male
      flank organs. The flank organ test demonstrated that 5 alpha-LNG activity was
      similar to that observed for levonorgestrel and testosterone (T) on
      gonadectomized male hamster flank organs. Topical applications of LNG or 5 alpha
      LNG increased [U-14C]glucose incorporation into lipids in a way similar to that
      of T. The overall data indicate that LNG and 5 alpha-LNG produced androgenic
      activity in the lipid pathway of male flank organs, and that 5 alpha-reduction is
      not essential for the LNG effect on this tissue.

PMID- 8545854
TI  - Derivatives of 4-styrylpyridines: synthesis, estrogen receptor binding affinity,
      and photophysical properties.
AB  - In order to develop novel ligands for the estrogen receptor (ER) that might have
      high binding affinity and fluorescence properties suitable for assaying ER levels
      in cells, we have prepared a series of substituted 4'-hydroxyl-styrylpyridines
      and phenylethylpyridines and studied their optical spectroscopy and receptor
      binding properties. Several derivatives that contain alkyl substituents on the
      internal ethene or ethane carbons were prepared. While most of these compounds
      have only modest affinity for ER, one fluorescent analog, (E)-1-(4-hydroxyphenyl)
      1-phenyl-2-(4-pyridinyl)ethene(13), has reasonably good binding affinity for ER
      and shows long wavelength fluorescence emission that is sensitive to solvent
      polarity and pH. This compound may prove to be a useful probe for detecting ER in
      cells.

PMID- 8545855
TI  - Biotransformation of corticosteroids by Penicillium decumbens ATCC 10436.
AB  - The biotransformation of a series of corticosteroids by the fungus Penicillium
      decumbens ATCC 10436 has been investigated. Conversion to the corresponding 5
      alpha-dihydrosteroid was observed for all the delta 4-3-ketosteroids studied with
      the exception of deoxycorticosterone, which was converted to a delta 1.4-diene.
      Deoxycorticosterone acetate was, however, converted to a 5 alpha-dihydro product
      concomitant with ester hydrolysis. Other substrates carrying a C-21 acetoxy group
      were also hydrolyzed to the alcohol. In two cases (resulting from
      deoxycorticosterone acetate and 11-deoxycortisone) the 5 alpha-3-keto product was
      further reduced to the 3 beta-alcohol. No reduction of delta 1.4-dienes was
      observed.

PMID- 8545857
TI  - Regulation of sex hormone-binding globulin production by isoflavonoids and
      patterns of isoflavonoid conjugation in HepG2 cell cultures.
AB  - The effect of the isoflavonoid phytoestrogens daidzein, equol, and genistein on
      sex hormone-binding globulin (SHBG) levels, SHBG mRNA transcript levels, and SHBG
      gene methylation was studied in HepG2 cell cultures by fluoroimmunometric SHBG
      assay and Northern and Southern hybridizations, respectively. The effect of 17
      beta-estradiol on these parameters was studied as a control. The metabolism of
      isoflavonoids in HepG2 cells was determined by isotope dilution gas
      chromatography-mass spectrometry, after ion-exchange chromatography. Daidzein and
      equol increased SHBG levels in parallel intracellularly and extracellularly,
      whereas genistein increased SHBG levels only within the cells, resembling thus
      the effect of 17 beta-estradiol. The difference may originate from the fact that
      genistein has more hydroxyl groups than daidzein and equol. The regulation of
      SHBG production by phytoestrogens appears to occur at the post-transcriptional
      level. Firstly, daidzein, equol, or genistein did not have a clear effect on the
      steady-state SHBG mRNA levels. Secondly, no effect on SHBG gene methylation was
      observed by genistein. The findings applied also to 17 beta-estradiol. However,
      as the SHBG gene was more methylated in SHBG-negative MCF-7 cells than in SHBG
      positive HepG2 cells, DNA methylation may play a role in the tissue-specific
      activation of this gene. The metabolism of isoflavonoids in HepG2 cells yielded
      mainly unconjugated and sulfated compounds. Similar metabolism in hepatocytes in
      vivo might retain their biological activity in tissues responsive to estrogens.

PMID- 8545858
TI  - [The hospital as provider of indigent care in the Middle Ages].

PMID- 8545856
TI  - The scarlet letter: Reichstein's Substance S. A comparison of the angiostatic
      properties of 5 alpha-tetrahydro S and 5 beta-tetrahydro S.
AB  - 5 beta-Tetrahydro-Reichstein's Substance S (3 alpha, 5 beta-THS) from different
      sources yielded variable bioassay activity in the chick chorio-allantoic membrane
      assay system. Physical characterization showed impure products. Synthesis of this
      compound by two different routes yielded active and inactive 3 alpha, 5 beta-THS.
      Of the other two epimers, 3 beta, 5 beta-THS (epi-THS) and 3 alpha, 5 alpha-THS
      (allo-THS), only the latter was active. These results suggest that the impurities
      present in 3 alpha, 5 beta-THS synthesized by reduction of the alpha, beta
      unsaturated ketone of Substance S might be either or both the epi-/allo-epimers
      (3 beta, 5 beta-THS and 3 alpha, 5 alpha-THS, respectively), with only the latter
      contributing the positive angiostatic activity to the mixture. Of the two
      synthetically derived compounds, only the latter was shown to maintain the
      activity, whereas 3 alpha, 5 beta-THS was not antiangiogenic.

PMID- 8545859
TI  - Proceedings of the 14th annual meeting of the American Society of Transplant
      Physicians. Chicago, Illinois, May 14-17, 1995.

PMID- 8545860
TI  - Reduced human IgG anti-ATGAM antibody formation in renal transplant recipients
      receiving mycophenolate mofetil.
AB  - Exposure to the equine-derived polyclonal antithymocyte preparation, ATGAM,
      frequently elicits human anti-ATGAM antibody formation. The influence of
      concomitant immunosuppressants on this antiantibody response has not been
      established. We therefore evaluated IgG antibody formation to ATGAM in 47
      patients receiving ATGAM as part of a prospective, randomized, double-blinded
      study of mycophenolate mofetil versus azathioprine for maintenance
      immunosuppression after primary cadaveric renal transplantation. All patients
      received ATGAM for induction of immunosuppression plus methylprednisolone,
      prednisone, and cyclosporine. In addition, patients were randomized to receive
      maintenance immunosuppression consisting of either azathioprine (AZA) 1-2
      mg/kg/day, mycophenolate mofetil 2 gm/day (MMF2), or mycophenolate mofetil 3
      gm/day (MMF3). Patient sequential sera were independently tested for IgG anti
      ATGAM antibody by 2 laboratories, which were blinded to treatment arm
      assignments, using enzyme-linked immunosorbent assays. Both laboratories found
      significantly greater anti-ATGAM antibody formation in group AZA compared with
      groups MMF2 and MMF3: laboratory 1 reported sensitization rates in the 3 groups
      of 94% (AZA), 50% (MMF2) (P < 0.02 vs. AZA), and 60% (MMF3) (P < 0.05 vs. AZA);
      and laboratory 2 reported rates of 67% (AZA), 17% (MMF2) (P < 0.02 vs. AZA), and
      10% (MMF3) (P < 0.02 vs. AZA). In addition, fewer patients formed high titer
      antibody in the MMF arms compared to the AZA arm: 56% (AZA), 0% (MMF2) (P < 0.02
      vs. AZA), and 20% (MMF3) (P < 0.02 vs. AZA) of patients for laboratory 1; and 20%
      (AZA), 0% (MMF2) (P < 0.05 vs. AZA), and 0% (MMF3) (P < 0.05 vs. AZA) of patients
      for laboratory 2. Differences in test results between the 2 laboratories were
      explained by differences in the sensitivity of their respective immunoassays and
      in the criteria used for assigning a positive result to test specimens. In this
      protocol, MMF at 2-3 gm/day was associated with a reduced incidence and titer of
      IgG anti-ATGAM antibody formation compared with standard azathioprine dosing.
      Although MMF previously has been reported to inhibit T cell responses that
      mediate acute cellular rejection, this is the first demonstration that MMF
      significantly inhibits human B cell responses to antigen in vivo.

PMID- 8545861
TI  - The relative effects of FK506 and cyclosporine on short- and long-term kidney
      graft survival.
AB  - As reported to the UNOS Kidney Transplant Registry from 1988 through 1994, 544
      first cadaveric kidney graft recipients have been discharged with maintenance
      tacrolimus (FK506) therapy. Total follow-up data was available on 38,057 first
      cadaveric kidney transplants from 224 centers reporting at least 10 grafts each
      to the Registry. We examined the effects of FK506 on short- and long-term renal
      graft outcomes and compared its effect with that of cyclosporine (CsA). Three
      drug categories (FK506, CsA, and Other) were defined using therapies through
      discharge (i.e., grafts surviving more than 15 days). The 1-year graft survival
      rate of 2366 recipients receiving Other therapies was 69.2 +/- 1.0%. By
      comparison, both FK506 and CsA recipients demonstrated significantly improved
      early graft function (1-yr survival rates of 91.1 +/- 1.3% and 86.6 +/- 0.2%,
      respectively). The long-term graft survival, as measured by half-lives, varied
      little (8-9 yr) between Other and CsA groups, but was significantly (P = 0.04)
      increased for FK506 patients (to approximately 14 yrs). CsA usage was reported by
      all 224 transplant centers, whereas FK506 was administered at only 24 (11%)
      centers. Using multivariate methods, a drug regimen's graft survival rate was
      adjusted for center effects and 19 covariates. The adjusted FK506 and CsA
      cadaveric graft survival rates at 1 and 3 years mirrored their unadjusted rates,
      indicating that demographic differences did not confound our results. Based on
      this study, FK506 appears to be the first therapeutic agent to significantly
      improve long-term kidney graft survival rates.

PMID- 8545862
TI  - Survival experience among elderly end-stage renal disease patients. A controlled
      comparison of transplantation and dialysis.
AB  - Renal transplantation is a relatively recent treatment option among the elderly
      with end-stage renal disease (ESRD). Since little is known regarding the clinical
      benefits of transplantation relative to dialysis in this age group, this study
      compares transplantation and dialysis among the elderly with respect to patient
      survival. Data utilized in this investigation were obtained from the Canadian
      Organ Replacement Register (CORR). The study population consisted of the 6400
      patients aged 60 and over at registration, diagnosed between 1987 and 1993, for
      whom data on comorbid conditions were available. Survival probability, death
      rates, age-standardized mortality ratios (SMRs) and Cox regression analysis were
      employed to evaluate the survival experience among the transplant and dialysis
      groups. Transplant recipients were matched (by age, underlying diagnosis leading
      to ESRD, and number of comorbid conditions) to 2 randomly selected patients who
      did not undergo transplantation. Using Cox regression, the time-dependent hazard
      ratio for transplantation versus dialysis patients was estimated at 0.47 (P <
      0.0001), indicating that even after adjusting for other known prognostic factors,
      elderly patients who received a transplant experienced significantly greater
      survival probability than those who remained on dialysis. When transplant
      patients were matched to randomly selected dialysis patients with the constraint
      that the corresponding dialysis patient have at least as much follow-up time as
      the transplant patient had waiting time, five-year survival rates were 81% and
      51% for the transplant and dialysis groups, respectively (P < 0.0001). These
      results support the potential advantage of transplantation among the elderly, and
      may have important implications for renal care in this age group.

PMID- 8545863
TI  - Donor-specific transfusions have long-term beneficial effects for human renal
      allografts.
AB  - From April, 1980 to November, 1988, 163 one or two haplotype-mismatch living
      related (LR) or living unrelated (LUR) potential renal transplant recipients
      received three 200 ml aliquots of donor specific transfusion (DST) at biweekly
      intervals with concomitant azathioprine (2 mg/kg/day). Following transplantation,
      only prednisone and azathioprine were given for immunosuppression. The results
      for the DST group are compared with those for HLA identical living recipients (57
      patients) transplanted during this same interval (1980-1988). Comparison is also
      made with a group of one or two haplotype-mismatched living donor recipients (54
      patients) not treated with DST but with triple drug therapy (prednisone,
      azathioprine, cyclosporine) and antithymocyte globulin (ATG) or OKT-3 induction.
      Permanent T cell crossmatch sensitization occurred in 11 of 163 patients (7%).
      Successful DST donor transplants were performed between 121 one HLA haplotype
      mismatched, 14 two HLA haplotype-mismatched LR, and 7 two haplotype-mismatched
      LUR pairs. Actual one- and five-year graft survivals were 94%, 100%, 100%, and
      72%, 85%, and 71%, respectively, for these three subgroups of DST treated
      patients. The graft survival for all DST pretreated recipients at one, five, and
      ten years was comparable to the HLA-identical group (94%, 79%, 64% vs. 91%, 80%
      and 77%). At a mean follow-up of 10 1/2 years, 54% (80 patients) of the entire
      group of 147 patients transplanted after DST have functioning transplants with a
      mean serum creatinine of 1.7 mg/dl. Fifteen percent of DST patients (21 patients)
      died with a functioning graft 2 to 132 months after transplantation, 26% (37
      patients) rejected the DST graft after 1 to 128 months, and 6% (9 patients) were
      lost for nonimmunological reasons. No lymphoproliferative disease developed in
      the DST group and the incidence of cytomegalovirus sepsis was only 2% (3
      patients). The long-term beneficial effects of DST on renal allograft survival
      and function and the lower incidence of the complications of nonspecific
      immunosuppression should encourage increased utilization of DST in renal
      transplantation.

PMID- 8545864
TI  - Donor race does not affect cadaver kidney transplant survival--a single center
      experience.
AB  - Black kidney transplant recipients have worse graft survival than white
      recipients. Speculation regarding etiology has focused on differences in human
      lymphocyte antigens (HLA). Some suggest that improvements in graft survival would
      be obtained if donor and recipient race were matched. We reviewed 236 cadaver
      transplants performed over 9 years at a single center using an HLA-match-driven
      allocation system and a uniform immunosuppressive protocol to determine the
      impact of donor race on graft survival. A multivariate analysis of graft survival
      using patient race, sex, age, transplant number, current and maximum plasma renin
      activity, donor race, cold ischemia time and HLA mismatch, the need for dialysis,
      and the presence of rejection as independent variables. Sixty percent of
      recipients were black, and 82% were primary transplants; 28 kidneys (12%) were
      from black donors. The 112 patients with the same race donor had identical 5-year
      graft survival as the 124 who had a different race donor (40%; P = 0.1726). The 5
      year survival of the 88 white recipients of white donor organs was better than
      that of the 120 black recipients of white donor organs (54% vs. 42%,
      respectively; P = 0.0398). Black recipients (t1/2 = 37 months) did worse than
      white recipients (t1/2 = 60 months) regardless of organ source (P = 0.023). In
      the multivariate analysis, neither donor nor recipient race were an independent
      variable in predicting graft survival. Rejection (RR = 2.9) and the need for
      dialysis on the transplant admission (RR = 4.1) were the only factors that
      predicted poor survival. Black recipients had more rejection (P = 0.04) but not
      more need for dialysis posttransplant regardless of donor race. Donor race did
      not affect graft survival in this series. The effect of recipient race on graft
      survival was due to an increased incidence of rejection episodes in black
      recipients, which was independent of HLA mismatch. These data suggest that
      improvements in immunosuppression, not changes in allocation, are needed to
      improve graft survival.

PMID- 8545865
TI  - Kidney-pancreas transplantation. The effect of portal versus systemic venous
      drainage of the pancreas on the lipoprotein composition.
AB  - We have previously shown that both kidney-alone and combined kidney-pancreas
      transplantation lower VLDL and IDL apoB while increasing LDL apoB, apoA-I, and
      HDL free cholesterol (FC). In this report, we analyze the lipoproteins of 31
      patients who have undergone combined kidney-pancreas transplantation. Systemic
      venous drainage of the pancreas was utilized in 20 of these patients while 11 had
      portal venous drainage. Six lipoprotein subfractions (VLDL, IDL, LDL, HDL-L, HDL
      M, HDL-D) were isolated by rapid gradient ultracentrifugation using a fixed-angle
      rotor. The apolipoprotein (by reverse-phase HPLC) and lipid (by enzymatic assays)
      composition of each subfraction was determined. After three months, there were
      few group differences. However, the portal group had substantial reductions in
      VLDL apoB at both six (-50% vs. +1%) and twelve months (-57% vs. +149%, P = .042)
      while the systemic group had increases in VLDL apoB. Similar differences were
      seen in IDL apoB (six months: -38% vs. +13%; twelve months: -61% vs. +56%, P =
      .008). LDL apoB increased in both groups at six months (portal: +7%; systemic:
      +30%) but fell in the portal group at twelve months (-17% vs. +41%, P = .0007).
      IDL triglyceride, cholesterol ester, phospholipids, and free cholesterol also
      fell by 19% to 47% in the portal group while they rose by 8% to 44% in the
      systemic patients, six and twelve months after surgery (P < .05). In addition,
      the VLDL and LDL free cholesterol to phospholipid ratios (FC/PL) fell (improved)
      by 16% to 26% in the portal patients while they rose by 9% to 28% in the systemic
      subjects during this time (P < .04). Finally, there were substantial improvements
      in the LDL composition of the portal patients compared to the systemic patients
      at six (PL/apoB: +23% vs. -16%, P = .005; CE/apoB: +14% vs. -14%, P = .037) and
      twelve months (PL/apoB: +39% vs. -13%, P = .011; CE/apoB: +41% vs. -15%, P =
      .011). These data indicate that portal drainage of the transplanted pancreas
      reduced the number of VLDL, IDL, and LDL particles, reduced the total mass of IDL
      (by 35%), and normalized the VLDL and LDL particle composition. These
      improvements were not seen in the patients who received systemic drainage of
      their pancreas. HDL-M also improved in the portal patients (TG: -29% vs. +12%, P
      = .025) (PL: +22% vs. -5%, P = .014) (total mass: +16% vs. +0.2%, P = .044) but
      not in the systemic patients six months after surgery. These results suggest that
      portal venous drainage of the pancreas leads to greater improvements in the
      lipoprotein composition of IDDM patients than does systemic drainage.

PMID- 8545866
TI  - Chronic renal allograft rejection in the first 6 months posttransplant.
AB  - Between May 1, 1986 and May 31, 1992 at the University of Minnesota, we
      interpreted 129 renal allograft biopsy specimens (done in 48 grafts during the
      first 6 months posttransplant) as showing changes consistent with chronic
      rejection. For this retrospective analysis, we reexamined these biopsies together
      with clinical information to determine: (a) whether a diagnosis other than
      chronic rejection would have been more appropriate, (b) how early posttransplant
      any chronic rejection changes occurred, and (c) if the diagnosis correlated with
      outcome. We found that (1) chronic rejection is uncommon in the first 6 months
      posttransplant; it was documented in only 27 (2.4%) of 1117 renal allografts and
      was preceded by acute rejection in all but 3 recipients (for these 3, the first
      biopsy specimen showed both acute and chronic rejection). (2) Chronic vascular
      rejection was seen in 1 recipient as early as 1 month posttransplant; the
      incidence increased over time and was associated with an actual graft survival
      rate of only 35%. (3) The most frequent cause of arterial intimal fibrosis in the
      first 6 months posttransplant was arteriosclerotic nephrosclerosis (ASNS) of
      donor origin. Long-term graft function for recipients with ASNS was 67%. (4)
      Early-onset ischemia or thrombosis was seen in 14 recipients and predicted poor
      outcome: only 35.7% of these recipients had long-term graft function. (5)
      Cyclosporine (CsA) toxicity was implicated in only 3 recipients, who had mild
      diffuse interstitial fibrosis in association with elevated CsA levels. Other
      variables (including systemic hypertension, urinary tract infection, obstructive
      uropathy, neurogenic bladder, cobalt therapy, and recurrent disease) were not
      significantly associated with chronic renal lesions in the first 6 months
      posttransplant. A significant number of biopsies were originally interpreted as
      showing chronic rejection, but the diagnosis was changed upon reevaluation in
      conjunction with clinical data. We conclude that many factors coexist to produce
      chronic lesions in biopsies during the first 6 months posttransplant, so clinical
      correlation is needed before establishing a diagnosis of chronic rejection.

PMID- 8545867
TI  - Impact of serum lipids on long-term graft and patient survival after renal
      transplantation.
AB  - The results after primary cadaveric renal transplantation in 665 consecutive
      patients were reviewed with respect to posttransplant serum lipids. Data were
      available for 182 of 665 patients on serum total cholesterol and triglycerides at
      1 year posttransplant. Hypercholesterolemia (cholesterol > 200 mg/dl) developed
      in 141 of 182 patients (77%) and hypertriglyceridemia developed in 73 of 166
      patients (44%). At 1 year posttransplant, hypercholesterolemia and
      hypertriglyceridemia both correlated with age at transplant (P = 0.0001, P =
      0.01). Hypercholesterolemia and hypertriglyceridemia were also correlated with
      obesity as determined by body mass index (kg/m2) (P = 0.006, P = 0.01).
      Hypertriglyceridemia at 1 year posttransplant correlated with pretransplant
      triglyceride level (P = 0.006), but hypercholesterolemia did not correlate with
      pretransplant cholesterol level (P = 0.53). Hyperlipidemia was not correlated
      with cyclosporine (CsA) or prednisone dose (mg/kg), CsA trough levels, number of
      rejection episodes, or serum creatinine at 1 year. Despite significant
      differences in serum cholesterol and triglycerides, actuarial graft and patient
      survival were similar between the normolipidemic and hyperlipidemic groups.

PMID- 8545868
TI  - Combined simultaneous kidney/bone marrow transplantation.
AB  - On the basis of observations in patients with long-term (28-30 years) renal
      allograft survival, all of whom had evidence of systemic microchimerism, we began
      a program of combined simultaneous kidney/bone marrow transplantation. Between
      12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8)
      unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and
      7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8
      years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia
      time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly
      because of refusal by the donor family to consent to vertebral body recovery; 3
      of these patients also received a pancreas. The mean recipient age was 47.9 +/-
      11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold
      ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based
      therapy, without radiation, cytoreduction, or induction antilymphocyte
      preparations. Blood was drawn prior to and at regular intervals after
      transplantation for detection of chimerism and for immunologic studies. With a
      mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33
      (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2
      mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any
      patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or
      ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of
      delayed graft function was 17%. A total of 18 (90%) control patients are alive,
      and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/-
      1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and
      10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20%
      (P = NS). In the study patients, chimerism was detected in the peripheral blood
      of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the
      control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P <
      .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable
      study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that
      combined kidney/bone marrow transplantation is associated with acceptable patient
      and graft survival, augmentation of chimerism, and no change in the early events
      after transplantation.

PMID- 8545869
TI  - Obesity as a risk factor after combined pancreas/kidney transplantation.
AB  - The impact of pretransplant overweight/obesity was analyzed in a group of 268
      consecutive primary pancreas renal transplant recipients. Obesity was defined as
      body mass index (BMI) greater than 27 kg/m2. BMI was available for 240 of the 268
      patients. A total of 88% (212/240) of the patients had a BMI < or = 27 and 28/240
      (12%) had BMI > 27. There were no significant differences in age, sex, or race
      between obese and nonobese patients. The incidence and degree of posttransplant
      hypertension, weight gain, increase in BMI, and hyperlipidemia did not differ on
      the basis of pretransplant BMI. Serum creatinine at one year posttransplant was
      slightly increased in obese patients, but the increase was not statistically
      significant. Cumulative prednisone dose (mg/kg) as well as cyclosporine (CsA)
      dose (mg/kg) at one year was not significantly different between obese and
      nonobese patients. However, there was a marginally significant negative
      correlation between BMI and one-year cumulative (mg/kg) prednisone dose (P =
      .06). Types and frequency of posttransplant complications were similar between
      obese and nonobese patients, although there was a slightly higher incidence of
      wound related complications in obese patients (11% vs. 6.8%) (P = NS). There was
      no difference in the frequency of acute rejection episodes in obese and nonobese
      patients. Actuarial patient survival was comparable between patients with BMI <
      or = 27 versus those with BMI > 27 (P = .10). However, actuarial graft survival,
      both pancreas and renal, were significantly decreased in patients with BMI > 27
      (P = .029). The decrease in pancreas and kidney graft survival in obese patients
      could not be attributed to decreased "early" patient survival, increased
      incidence of perioperative or postoperative complications, differences in
      hypertension, acute rejection episodes, serum lipids, or immunosuppression
      dosage. The most common causes of graft loss were rejection and patient death in
      both obese and nonobese patients. After three years posttransplant, the decreased
      pancreas and renal graft survival in obese patients corresponded to decreased
      patient survival. The most common cause of patient death was cardiovascular
      complications in both obese and nonobese PKT recipients.

PMID- 8545870
TI  - Experience with protocol biopsies after solitary pancreas transplantation.
AB  - The early detection of allograft rejection remains elusive after solitary
      pancreas transplantation (PTX). We have previously described a modified technique
      of cystoscopic transduodenal PTX biopsy using the Biopty gun under ultrasound
      guidance. During the last 2 years, we performed 24 solitary PTXs with prospective
      protocol biopsy monitoring as well as biopsies performed whenever clinically
      indicated. The study group included 17 pancreas transplants alone, 6 sequential
      pancreas after kidney transplants, and 1 sequential pancreas after liver
      transplant. Five patients received pancreas retransplants. A total of 92
      cystoscopically directed core PTX biopsies were performed, including 50 protocol
      biopsies (mean 2.1 per patient). Protocol biopsies were performed at 1 month
      (19), 2 months (3), 3 months (20), 6 months (7), and 12 months (1) after PTX.
      Adequate PTX tissue for histopathologic examination was obtained in 49 cases
      (98%). Biopsy findings included no rejection (34), mild rejection (13),
      pancreatitis (1), and cytomegalovirus infection (1). Overall, 15 of the 49
      evaluable biopsies (31%) had significant histopathologic findings. All but 1 of
      the cases of mild rejection were treated with bolus steroids. Eight of these
      patients subsequently developed recurrent biopsy-proven rejection within 2
      months; 5 grafts were subsequently lost to rejection between 3 and 13 months
      after PTX. Three biopsy complications occurred: 1 hematoma, 1 pancreatitis, and 1
      ileus. Patient survival is 96% and PTX graft survival (complete insulin
      independence) is 75% after a mean follow-up of 15 months. In the remaining 42
      clinically indicated biopsies, 3 were insufficient, 8 showed no rejection, and 31
      (79%) had rejection. In half of these cases, the rejection was graded as moderate
      to severe. In conclusion, prospective monitoring with protocol PTX biopsies may
      result in the earlier detection of allograft rejection and have a direct effect
      on improving results after solitary PTX.

PMID- 8545871
TI  - Absorption characteristics of a microemulsion formulation of cyclosporine in de
      novo pediatric liver transplant recipients.
AB  - In pediatric liver transplant recipients, oral cyclosporine (CsA) therapy may be
      complicated by impaired or delayed absorption during the initial weeks
      posttransplant. Neoral (NL) is a microemulsion preconcentrate formulation of CsA
      expected to increase the rate and extent of absorption of CsA and have less
      pharmacokinetic variability. The absolute bioavailability (F) of CsA from NL was
      compared with that of the currently marketed Sandimmune (SM) formulation in a
      double-blind, crossover study conducted in 9 pediatric liver transplant
      recipients (age 6 months to 11 years) between 8 and 20 days posttransplant. After
      determination of CsA pharmacokinetics for a steady-state intravenous dose,
      patients were randomized to receive a single oral dose of NL or SM in period I
      and the alternative formulation in period II. Clearance (Clt) and volume of
      distribution (Vss) values (mean +/- s.d.) calculated from the i.v. dose were
      similar to that previously reported for pediatric patients (Clt = 12.0 +/- 1.3
      ml/min/kg; Vss = 2.2 +/- 0.2 L/kg). Mean F (+/- SD) for NL was significantly
      higher than SM (NL = 37.6 +/- 14.6%; SM = 24.7 +/- 8.0%; P = 0.05). Although not
      reaching statistical significance, the observed maximum blood concentration
      (Cmax) was higher, and the time to Cmax (Tmax) was shorter for NL in 8 or 9
      patients. There were no significant correlations between age and any
      pharmacokinetic parameter for the group as a whole--however, there were
      statistically significant correlations between age and F for NL (r = 0.87; P =
      0.02), and for age and Vss (r = 0.91; P = 0.01) for the 6 patients aged 2 years
      or less. In this pediatric liver transplant population, Neoral demonstrated
      improved absorption (% increase in F) compared to Sandimmune. In liver transplant
      recipients aged 2 years or less, absorption of Neoral may be a function of age
      and/or bowel length.

PMID- 8545872
TI  - A randomized prospective trial of steroid withdrawal after liver transplantation.
AB  - The safety of steroid withdrawal in orthotopic liver transplant (OLT) recipients
      has been studied in a prospective trial with a comparison control group. Sixty
      four recipients of ABO-compatible grafts (42 adults, 22 children) were randomized
      into a steroid withdrawal (SW) group and a control group. Inclusion criteria
      included survival > one year post-OLT and no rejection > six months after OLT.
      Exclusion criteria included previous graft loss secondary to rejection, > two
      episodes of documented rejection, patients transplanted for autoimmune hepatitis,
      and patients unable to receive azathioprine. Target HPLC cyclosporine levels in
      both groups were 100-200 ng/ml. Thirty-three patients entered the SW group and 31
      the control group at a mean of 3.5 years after OLT; follow-ups were 592 and 527
      days, respectively. Two patients in each group developed biopsy-proven rejection.
      In the SW group one patient rejected at three months, the other at nine months.
      Both rejection episodes resolved with only reinstitution of oral prednisone. Of
      the two patients who rejected in the control group (one at 7 months, one at 11
      months) one required conversion to tacrolimus and the other intravenous steroids.
      There were no significant differences between the two groups for prednisone,
      azathioprine, cyclosporine doses, cyclosporine levels, liver function tests, and
      white blood cell counts at base line compared with 12 months. Fasting serum
      cholesterol in the SW group decreased from 194 +/- 44 mg/dl at baseline to 175 +/
      37 mg/dl at one year, whereas in the control group cholesterol rose from 180 +/-
      48 mg/dl to 193 +/- 44 mg/dl. In pediatric patients no significant difference in
      age-adjusted height velocities over one year was seen between the two groups. We
      concluded that dual therapy with cyclosporine and azathioprine in stable long
      term liver allograft recipients is not associated with an increase in rejection
      incidence. Prednisone withdrawal may be associated with an improvement in lipid
      profiles.

PMID- 8545873
TI  - Vascular endothelial growth factor expression in transplanted human hearts.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen
      thought to play an important role in coronary collateral vessel formation. We
      used immunocytochemistry to determine VEGF expression in biopsies (n = 283) of
      transplanted human hearts (n = 109) with and without microvascular fibrin.
      Measures of vascular fibrin, alpha 2 plasmin-inhibitor (a2Pl), macrophages,
      neutrophils, and serum cardiac troponin T titers were used to evaluate myocardial
      damage. Antibody to T lymphocytes was used to evaluate cellular rejection, and
      HLA-DR, ICAM-1, and PAL-E antibodies were used to assess endothelial cell
      activation and phenotypic changes in the microcirculation. No VEGF
      immunoreactivity was detected in control donor hearts without fibrin, but the
      proportion of biopsies demonstrating VEGF immunoreactivity increased
      significantly in allografts with increasing fibrin and a2PI reactivity (P =
      0.0001). VEGF immunoreactivity was confined to areas of fibrin deposition and was
      associated with infiltrates of macrophages and neutrophils (P < 0.0001), but not
      with T cells (P = 0.10). Biopsies with fibrin/VEGF reactivity were associated
      with increased capillary endothelial cell HLA-DR, ICAM-1, and PAL-E reactivity.
      In a subset of patients, serum cardiac troponin-T values were greater in patients
      with VEGF-positive (n = 21) than VEGF-negative (n = 19) biopsies (P = 0.05).
      Nested RT-PCR demonstrated that biopsies with and without fibrin/VEGF
      immunoreactivities expressed VEGF121, VEGF165, and VEGF189 variants, with VEGF165
      being the dominate variant. These results indicate that endogenous VEGF is
      expressed locally following vascular thrombosis and myocardial cell damage, and
      that VEGF expression may be related to endothelial cell activation and phenotypic
      changes found in the microcirculation of cardiac allografts.

PMID- 8545874
TI  - The utility of annual surveillance bronchoscopy in heart-lung transplant
      recipients.
AB  - Bronchoscopy with transbronchial biopsy (TBBx) and bronchoalveolar lavage (BAL)
      has an appreciable yield in detecting asymptomatic abnormalities in heart-lung
      transplant recipients (HLTR) during the early postoperative period. The utility
      of annual surveillance procedures has not been critically evaluated. We reviewed
      all annual bronchoscopies performed on 29 HLTR to determine the frequency of
      asymptomatic abnormalities. Surveillance bronchoscopies (SB) were performed on
      asymptomatic subjects with unchanged lung function compared with baseline.
      Surveillance/clinical bronchoscopies (SCB) were those performed in patients with
      stable decrements in lung function. Nineteen patients underwent 48 SB and 8 had
      18 SCB. Five of 15 (33%) SB performed at one year yielded an abnormal TBBx (1
      grade 2 acute rejection [AR], 1 grade 1 AR, 1 grade 1 AR with obliterative
      bronchiolitis [OB] and 2 Pneumocystis carinii pneumonia). At 2 or more years,
      TBBx was abnormal in 2 of 33 (6%, p = 0.024 compared with first year TBBx) (1
      grade 1 AR, 1 lymphocytic bronchiolitis). Pathogens were identified in BAL in 19
      (40%) SB. Fourteen (78%) SCB were abnormal. Nine (50%) revealed an abnormal TBBx
      (all OB), but only 2 (11%) of these altered patient management. Seven (39%)
      demonstrated pathogens in BAL. We conclude that in HLTR (1) surveillance TBBx
      rarely yields positive findings 2 or more years posttransplant, (2) surveillance
      TBBx seldom alters management in patients with stable decrements in lung
      function, and (3) BAL is useful to screen for potential pathogens.

PMID- 8545875
TI  - Psychosocial evaluation and prediction of compliance problems and morbidity after
      heart transplantation.
AB  - We examined prospectively determined psychosocial evaluation data in 125
      consecutive adult patients undergoing heart transplantation from January 1992 to
      April 1994 to determine their associations with morbidity, mortality, and
      compliance. Prospective ratings included age, sex, weight, education, social
      support, living arrangements, motivation, knowledge and expectations about
      transplantation, intercurrent social stressors, substance abuse, personality
      disorder, cognitive impairment, other psychiatric disorders, and the evaluating
      psychiatrist's global assessment of psychosocial risk. Additional variables
      evaluated were support group attendance and waiting list time. We examined
      outcomes including patient survival, compliance, episodes of rejection and
      infection, development of transplant coronary artery disease, number of missed
      appointments, and maintenance of ideal body weight. The posttransplant follow-up
      period was 13.8 +/- 9.9 months (mean +/- SD). In univariate analyses, compliance
      problems were associated with substance abuse history (P = .0007), personality
      disorder (P = .007), living arrangements (P = .02), and global psychosocial risk
      (P = .001). The number of rejection episodes was associated with global
      psychosocial risk (P = .029), and transplant coronary artery disease was
      inversely associated with education (P = .01). Survival was not associated with
      any of the predictor variables. In stepwise multivariate analyses, the
      significant predictors of compliance were substance abuse (odds ratio 3.69,
      confidence limits 1.07-12.71) and global psychosocial risk (odds ratio 3.76,
      confidence intervals 1.18-11.97). These findings suggest that pretransplant
      evaluation of psychosocial risk factors can identify patients with increased risk
      of postoperative noncompliance and morbidity.

PMID- 8545876
TI  - Ventricular remodeling following infant-pediatric cardiac transplantation. Does
      age at transplantation or size disparity matter?
AB  - Early left ventricular (LV) remodeling following pediatric cardiac
      transplantation has not been described. To identify patterns and determinants of
      change in left ventricular mass and volume posttransplant, we studied 125
      consecutive children who underwent cardiac transplantation between January 1,
      1989 and July 31, 1993. Two-dimensional imaging-directed M-mode echocardiograms
      were studied weekly until 26 weeks post-transplant. LV mass and volume (indexed
      to BSA1.5) were measured. LV mass index increased until 3 weeks post-transplant,
      and then decreased. The mean decrement in LV mass index after 8 weeks post
      transplant (relative to baseline) was significantly larger in patients with donor
      recipient weight ratio > 1.5 compared with patients with donor-recipient weight
      ratio < or = 1.5 (-2.2 g/m3 compared with 33.4 g/m3, respectively, P < 0.01).
      Multiple linear regression was performed employing donor-recipient weight ratio,
      time since transplantation, ischemic time, and age at transplant as prognostic
      variables. Donor-recipient weight ratio (P < 0.0001), time since transplant (P <
      0.01), and age at transplant (P = 0.02) were identified as independent predictors
      of change in LV mass index. Donor-recipient weight ratio (P = 0.001) and time
      since transplantation (P = 0.02) were independent predictors of change in LV
      volume index. There was an interaction between donor-recipient weight ratio and
      time since transplantation, suggesting that donor-recipient weight ratio has an
      independent effect as well as a time-dependent effect on change in LV mass and
      volume indices. LV mass and volume indices increased early posttransplant and
      then decreased; this pattern was temporally predictable, and dependent on donor
      recipient weight ratio and age at transplant.

PMID- 8545877
TI  - Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus
      infections after heart transplantation.
AB  - Cytomegalovirus (CMV) infection is associated with an increased incidence of
      other opportunistic infections in organ transplant recipients. Whether this is
      related to immunomodulating effects of CMV or independent of CMV but associated
      with a host risk factor common to both infections is unclear. The purpose of this
      study was to determine whether the reduction in CMV infections seen with
      prophylactic ganciclovir treatment after heart transplantation is associated with
      a reduced incidence of other opportunistic infections. Of 149 patients
      prospectively enrolled in a multicenter, randomized, double-blind, placebo
      controlled trial of ganciclovir to prevent CMV disease, 74 patients enrolled at
      this center (33 control and 41 ganciclovir-treated) were retrospectively
      identified. All received prophylactic OKT-3 and standard 3 drug maintenance
      immunosuppressive therapy. Actuarial survival and rejection rates and incidence
      of opportunistic infections (bacterial, fungal, and protozoal) for the 2
      treatment groups were determined and compared using Cox-Mantel analysis. CMV
      disease occurred 2.5 times more frequently in the control group. There were no
      significant differences in survival or rejection rates nor in bacterial or
      protozoal infection incidence between the 2 groups. Bacterial infections occurred
      in 54% of control and 39% of ganciclovir-treated patients (P = 0.18). There were
      significantly fewer fungal infections in the ganciclovir-treated group (7% vs.
      27%, P = 0.0071). CMV and fungal infections were both significantly reduced in
      patients who received ganciclovir prophylaxis. This suggests that active CMV
      disease may be causally associated with the development of opportunistic fungal
      infections.

PMID- 8545878
TI  - The relationship of granzyme A and perforin expression to cardiac allograft
      rejection and dysfunction.
AB  - The mechanisms underlying contractile dysfunction following heart transplantation
      are poorly defined. To investigate the role of cytotoxic T cells (CTL) in cardiac
      transplant rejection, and during episodic contractile dysfunction, we performed a
      prospective study analyzing the expression of granzyme A and perforin, two
      functional markers of activated CTL. Sixteen consecutive patients were analyzed
      during the first year posttransplantation. All patients received induction
      therapy with OKT-3 and received standard three-drug immunosuppression therapy.
      Rejection status was monitored using routine surveillance endomyocardial biopsy
      and graded according to the ISHLT scale. Granzyme A and perforin mRNA were
      detected by reverse transcription PCR at the time of each routine biopsy. A total
      of 64/123 biopsies were positive for granzyme expression, while 38/123 samples
      were positive for perforin expression. LV function was monitored using M-mode
      derived fractional shortening and Doppler assessment of diastolic function
      (isovolumic relaxation time [IVRT] and pressure half-time [P1/2]). As expected,
      the presence of granzyme A message was associated with rejection score (ANOVA, P
      = 0.001). In addition, granzyme A expression was correlated with a decrease in
      diastolic function (chi 2 = 6.4, P < 0.02), but was not associated with systolic
      function. The presence of perforin message was not correlated with functional
      changes or with rejection grade, but was associated with granzyme expression (chi
      2 = 9.11, P = 0.0025). These studies suggest that the presence of granzyme A
      message may be an important predictor of graft function.

PMID- 8545879
TI  - Sarcomas in organ allograft recipients.
AB  - In a review of 8724 de novo malignancies that occurred in 8191 organ allograft
      recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and
      other sarcomas (OS) 1.7% a much higher proportion than in the general population.
      KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of
      patients with KS the lesions were confined to the skin and/or oropharynx while
      40% involved internal organs and/or lymph nodes. Complete remissions following
      various treatments occurred in 53% of the former group and 27% of the latter. In
      both groups 32% and 60% of remissions, respectively, occurred when the only
      treatment was reduction or cessation of immunosuppressive therapy. However, this
      treatment caused impaired function or allograft loss from rejection in 22 of 34
      kidney recipients. Recurrent KS occurred in 5% of patients in remission when
      immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human
      immunodeficiency virus were positive. Most OS arose in internal organs or soft
      tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma
      (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8),
      undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were
      noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal
      (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15
      (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms
      at sites of arteriovenous fistulas used for pretransplant hemodialysis access.
      One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas.
      One patient with mesothelioma had a history of asbestos exposure and two others
      had possible exposure.

PMID- 8545880
TI  - The risks, benefits, and costs of expanding donor criteria. A collaborative
      prospective three-year study.
AB  - The study purpose was to identify risks, benefits and costs associated with an
      expanded donor protocol. The protocol design evaluated organs rescued using
      expanded donor criteria and weighed all costs associated with doing so. Costs
      were measured against conditions experienced with expanded and traditional
      criteria and recipient outcome. Traditional donors were between 5 and 55, with
      negative serologies, and no history of hypertension or diabetes. "Expanded
      donors" were between 55 and 75 or less than 5, with a history of hypertension,
      diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met
      criteria from which 200 organs were transplanted. Defined costs and outcomes for
      recipients were tracked. Using expanded criteria: costs averaged 20% more per
      organ; OPO personnel spent an average of 6 hours more time on-site; an additional
      12-14 hours in placement activity; and average organs per donor decreased. Heart
      patient and graft survival rates for traditional and expanded donor organs were
      comparable. Kidney patients transplanted from this pool experienced a decrease in
      patient (P = .14) and a significant decrease in graft (P = .02) survival rates.
      Patient (P = .05) and graft (P = .01) survival rates were significantly lower in
      liver patients transplanted with expanded donor organs. Two hundred transplants
      occurred using expanded donor criteria. Costs for the OPO increased appreciably.
      Heart and kidney utilization from these donors seems justified. It is thought
      that liver recipients' results were due to utilizing them in sicker patients.
      Recovery of organs from donors using expanded criteria appears to be a reasonable
      way of increasing organ supply.

PMID- 8545881
TI  - Genetic control of the humoral immune response to xenografts. I. Functional
      characterization of rat monoclonal antibodies to hamster heart xenografts.
AB  - The rejection of cardiac xenografts in the hamster-to-rat combination is
      characterized by the production of IgM antibodies that result in the rapid loss
      of the graft. We have recently produced rat monoclonal antibodies (mAb) to
      hamster heart xenografts in an attempt to develop reagents for use in identifying
      the target antigens for this reaction and to study the nature of the genetic
      control of the humoral response. The monoclonals were created by the fusion of
      myeloma cells with splenic lymphocytes from LEW rat recipients of hamster cardiac
      xenografts. The hybridomas were screened for antibody production, reactivity to
      hamster cell surface antigens, and the ability to mediate hyperacute rejection of
      hamster heart xenografts. A panel of monoclonal antibodies has been identified
      that are capable of inducing hyperacute rejection. All of these mAbs are IgM and
      bind strongly to hamster vascular endothelium. None of the mAbs were
      lymphocytotoxic or bound to hamster lymphocytes or erythrocytes. Immunopathologic
      studies demonstrated that these mAbs react specifically with hamster vascular
      endothelium and mediate a complement-dependent humoral reaction leading to the
      destruction of the cardiac xenografts. One of the mAbs (designated as HAR-1) has
      been characterized in detail. HAR-1 detects antigens distributed in the vascular
      endothelium, epithelium of bronchi in the lung, small intestine, tubules of
      kidney, and selective components of lymphoid organs--e.g., the stromal cells of
      the spleen and thymic medullary epithelium. Western blot analysis of hamster
      heart proteins with HAR-1 showed multiple bands with two major bands migrating at
      80 kDa and 48 kDa. Absorption of the HAR-1 antibody with 48 individual
      carbohydrate molecules demonstrated that the strongest reactivity of the antibody
      is with a sialyl-Lea carbohydrate antigen.

PMID- 8545882
TI  - Genetic control of the humoral immune response to xenografts. II. Monoclonal
      antibodies that cause rejection of heart xenografts are encoded by germline
      immunoglobulin genes.
AB  - The early phases of the rejection of xenografts exchanged between closely related
      species are dominated by a vigorous humoral immune response. We have recently
      used a linker-mediated polymerase chain reaction (LM-PCR) to generate Ig heavy
      and light chain-specific cDNA libraries to examine the Ig gene control of a
      prototypic IgM monoclonal antibody, HAR-1, that causes the hyperacute rejection
      of hamster xenografts. Recombinant clones from the library were screened directly
      from bacterial colonies by PCR and the nucleic acid sequences of the clones
      established. Our results demonstrate that the HAR-1 hybridoma is encoded by Ig VH
      and JH genes in a germline configuration. Comparison of the cDNA sequence for HAR
      1 VH with the germline equivalent of this gene isolated from newborn LEW liver
      (provisionally designated VHHAR-1) showed that the two VH sequences share a
      nucleic acid identity of 99.3%. Similarly, the HAR-1 monoclonal uses a Ig JH gene
      that is 98.2% identical with the JH1 nucleic acid sequence available in the
      GeneBank. The use of Ig VH and JH genes in a germline configuration is similar to
      that seen with polyreactive natural antibodies to infectious agents and
      autoantibodies. These humoral responses are thought to be the result of the
      stimulation of a T cell-independent subset of B cells, the B-1a/B-1b subset, that
      is responsible for producing antibodies that serve as a primitive humoral
      (natural antibody) defense mechanism against infectious diseases. Our results
      suggest that the humoral component of the rejection of xenografts in the hamster
      to-rat model may represent the stimulation of this type of B cell antibody
      response by xenogeneic target antigens that share antigenic epitopes with
      bacteria and other infectious agents.

PMID- 8545883
TI  - Prevention of graft-versus-host disease and the induction of transplant tolerance
      by low-dose UV-B irradiation of BM cells combined with cyclosporine
      immunosuppression.
AB  - GVHD is prevented and stable chimerism is induced in the rat BMT model by 700
      J/m2 but not 100-500 J/m2 UV-B irradiation of allogeneic BM cells. Paradoxically,
      CsA which prevents GVHD in clinical BMT causes an aggressive autoimmune disease
      termed syngeneic GVHD in irradiated syngeneic BMT recipients after its
      withdrawal. Recently, we have shown that while 500-700 J/m2 UV-B irradiation of
      syngeneic BM cells combined with a 30-day course of CsA recipient
      immunosuppression impairs hemopoiesis due to lack of hemopoietic factors, a low
      dose of 100-300 J/m2 UV-B is effective in preventing CsA-induced autoimmune
      disease without endangering BM engraftment. This study extends these findings to
      the P-to-F1 hybrid and fully allogeneic rat BMT models and examines the
      effectiveness of low-dose UV-B irradiation of BM cells combined with a short
      course of CsA treatment in the prevention of GVHD and induction of transplant
      tolerance. Lethally gamma-irradiated (10.5 Gy) LBNF1 recipients of naive or UV-B
      irradiated (100-700 J/m2) BMT were treated with CsA (12.5 mg/kg/day) for 30
      consecutive days after BMT. All lethally irradiated LBNF1 that did not receive
      BMT died in < 16 days, while animals transplanted with UV-B (700 J/m2) BMT
      survived > 1 year without GVHD. In contrast, all recipients of naive BMT died of
      lethal GVHD in < 50 days. Similarly, all recipients of naive BMT that received a
      30-day course of CsA therapy developed severe GVHD with 60% mortality after
      cessation of CsA therapy. CsA-treated recipients of BMT irradiated with 700 J/m2
      died between 12 and 25 days from failure of hemopoiesis. In contrast, CsA-treated
      recipients of 100-200 J/m2 UV-B irradiated BMT showed full BM engraftment without
      GVHD after cessation of CsA and survived > 1 year. These results were
      reproducible in the fully allogeneic UV-B BMT model. To test for donor-specific
      tolerance, the animals challenged 100 days after BMT with cardiac allografts
      accepted permanently (> 100 days) Lewis but not BN (non-BMT parental donor)
      cardiac allografts. Our results confirm that 700 J/m2 UV-B irradiation of BM
      cells combined with CsA recipient immunosuppression impairs the recovery capacity
      of stem cells while the use of lower UV-B (100-200 J/m2) is effective in
      preventing CsA-induced autoimmune disease without endangering BM engraftment and
      leads to induction of transplant tolerance.

PMID- 8545884
TI  - Downregulation of intragraft IFN-gamma expression correlates with increased IgG1
      alloantibody response following intrathymic immunomodulation of sensitized rat
      recipients.
AB  - A single intrathymic injection of donor-specific spleen cells (2 x 10(7))
      abrogates accelerated (24 hr) rejection of LBNF1 cardiac allografts in
      presensitized LEW rats and prolongs graft survival to about 11 days. This effect
      is donor-specific, gamma-irradiation-sensitive, thymus-dependent, and requires no
      concomitant therapy. We have recently shown that following intrathymic
      alloantigen administration, there is an earlier and increased systemic production
      of alloreactive IgM, and subsequently a premature isotype switching to IgG with
      the predominant IgG1 and IgG2a alloantibody responses. There is also a
      preferential binding of these IgG subclasses to the endothelium of well
      functioning allografts. In this work, we analyzed the early cell activation and
      related cytokine elaboration patterns at the mRNA and protein levels by
      competitive template RT-PCR and immunohistochemistry, respectively. We found that
      prolonged cardiac allograft survival following intrathymic administration of
      donor spleen cells in presensitized rats was associated with markedly depressed
      intragraft IFN gamma mRNA and protein expression. Moreover, intrathymic
      allostimulation has led to a defect in the IL-2 pathway as the expression of IL-2
      and IL-2R protein at the graft site was inhibited despite stable IL-2 mRNA
      levels. The inhibition of cell activation was also demonstrated by reduced MHC
      class II and the lack of ICAM-1, and TNF-alpha expression by
      immunohistochemistry. The expression of biologically active IL-12 (p70) by
      mononuclear and endothelial cells was detected in rejecting grafts between 3 and
      12 hr. The well-functioning grafts after intrathymic allostimulation were devoid
      of IL-12 (p70), which in turn may have contributed to the downregulation of IFN
      gamma mRNA and protein. Treatment with r.IFN-gamma, but not with r.IL-2,
      recreated the rejection response, and the characteristic IgG subclass pattern
      associated with accelerated graft loss. Hence, intrathymic immunomodulation with
      alloantigen results in selective inhibition of IFN-gamma-producing cells and a
      preferential upregulation of IgG1 alloantibodies. These data support the notion
      of the interlocked immunoregulatory roles of cytokine and alloantibody networks
      in rat allograft recipients.

PMID- 8545885
TI  - Binding of activated protein C to a specific receptor on human mononuclear
      phagocytes inhibits intracellular calcium signaling and monocyte-dependent
      proliferative responses.
AB  - Upon activation, mononuclear phagocytes (Mphi) play key roles in the development
      of septic shock and multiple host immune responses, but details of the regulation
      of Mphi activation are little understood. We recently showed that the physiologic
      anticoagulant molecule, activated protein C (APC), blocks responses of human
      blood Mphi, alveolar Mphi, or THP-1 cells induced by LPS, IFN-gamma, or PMA,
      including TNF-alpha production and down-regulation of several LPS binding-related
      proteins. We now report a possible mechanism of action through inhibition of the
      rapid intracellular calcium signaling that occurs at the onset of Mphi
      activation, and characterization of a specific Mphi receptor for APC. Flow
      cytometry studies using Fluo-3 showed that Mph activation by Fc-receptor cross
      linking or rIFN-gamma caused a rapid increase in free intracellular calcium, a
      primary event in multiple signal transduction pathways, which was blocked by
      pretreatment with APC. Consistent with this, addition of APC inhibited PHA
      induced T cell proliferation in a dose- and time-dependent manner. Peak
      suppression (> 70%) required addition of APC within the first hour of 72 hr
      cocultures of Mphi and lymphocytes, and proliferative responses were not restored
      by addition of IL-2 or TNF-alpha. Biochemical studies showed that 125I-labeled
      APC bound specifically to M phi in a time-dependent and saturable manner.
      Scatchard analysis indicated there were 180,690 binding sites for APC per cell,
      which were of high affinity (Kd value of 12.9 mM). Binding of 125I-APC was
      doubled by activation of Mphi with LPS, and bound APC was not displaced by the
      zymogen, protein C (PC), or by enzymatically inactive (diisopropyl
      fluorophosphate- or PPACK-treated) APC, indicating an absolute requirement for
      the active site of APC in its binding to Mphi. APC binding was blocked by a
      polyclonal Ab to human PC/APC, but not by protein S, factor Va or Xa, or a
      polyclonal antithrombomodulin antibody. When 125I-APC was crosslinked to its
      receptor, immunoprecipitated and analyzed by SDS-PAGE under reducing conditions,
      a covalent complex (110-115 kD) of 125I-APC (62 kD) and its receptor was seen. In
      addition, a Mphi membrane protein of 50-55 kD, as determined by SDS-PAGE, was
      affinity-purified using an APC-Affigel column, and confirmed by ligand binding.
      Taken together, our findings document the presence of a M phi surface receptor
      for APC, which appears distinct from a recently described endothelial receptor
      for PC and APC, and which may be involved in the inhibitory effects of APC on
      activation of human Mphi, including Mphi-dependent T cell proliferation.

PMID- 8545886
TI  - Expression of cytokines and immune mediators during chronic liver allograft
      rejection.
AB  - To determine the immune processes involved in chronic liver allograft rejection
      (CR) we examined in situ cytokine production in tissue from 15 patients with both
      clinical and histopathological diagnoses of CR. Total RNA was isolated from liver
      samples, reverse-transcribed and analyzed by RT-PCR for the production of
      proinflammatory cytokines and immunoregulatory mediators. Transcripts for the Th1
      like cytokines IL-2 and IFN-gamma were detected in 53.3% and 46.7% of CR grafts,
      while they were detected in only 16% and 0% of stable grafts, respectively. The
      cytotoxic T cell mediator granzyme B was expressed in the majority of liver
      grafts undergoing CR, but was expressed only in a minority of stable grafts (80%
      vs. 16%, P < 0.05). The T cell product IL-5 was also significantly upregulated in
      CR as compared with stable livers (80% vs. 16%, P < 0.01). Other Th2 cytokines-
      IL-4 and IL-10--and macrophage products--IL-1 beta, IL-6, IL-8, TGF-beta, and TNF
      alpha--were not substantially upregulated in CR grafts as compared with stable
      grafts. PDGF-beta transcripts were detected in the majority of the CR grafts, but
      were not detected in stable liver grafts (73% vs. 0, P < 0.05). By
      immunohistochemical staining, we observed that CD3+CD4+, and CD3+CD4- T cells
      were detected in CR grafts along with CD20+ B cells and CD68+ macrophages. There
      was, however, a predominant infiltration of CD3+CD4+ lymphocytes. Taken together,
      these data suggest that infiltrating cells produce proinflammatory and
      immunoregulatory cytokines that have a role in mediating graft damage in CR.

PMID- 8545888
TI  - Organ-specific patterns of donor antigen-specific hyporeactivity and peripheral
      blood allogeneic microchimerism in lung, kidney, and liver transplant recipients.
AB  - Although their relative importance and interaction are unclear, donor
      antigen(Ag)*-specific hyporeactivity and allogeneic microchimerism have been
      associated with improved long-term graft outcome and a lower incidence of chronic
      rejection in solid organ transplant recipients. We have postulated that a
      critical level of donor antigen, for a critical time period, is necessary to
      develop and maintain donor antigen-specific hyporeactivity; both the level and
      the time may differ by organ transplanted. In our current study, we tested donor
      antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in
      liver and kidney recipients and compared these values with our previous findings
      in lung recipients. We tested 25 liver recipients at 12 to 29 months
      posttransplant: 10 (40%) had developed donor antigen-specific hyporeactivity; 5
      (20%), peripheral blood allogeneic microchimerism. For all but 1 of the chimeric
      and hyporeactive recipients, the level of donor cells was very low (< 1:20,000).
      Five hyporeactive recipients and all 15 donor antigen-responsive recipients did
      not have detectable levels of peripheral blood microchimerism. No chronic
      rejection has developed in any of these recipients to date--however, a lower
      incidence of acute rejection was observed for those recipients with donor antigen
      specific hyporeactivity (30% versus 60% without) or with peripheral blood
      allogeneic microchimerism (20% versus 55% without) (P = ns). These results differ
      from our previous findings in 19 lung recipients: at 12 to 18 months
      posttransplant, 35% of them had developed donor antigen-specific hyporeactivity;
      47%, peripheral blood allogeneic microchimerism. All donor antigen-specific
      hyporeactivity recipients as well as some donor antigen-responsive recipients had
      peripheral blood allogeneic microchimerism. We expanded our current study to
      include 26 recipients and a quantitative estimate of the level of allogeneic
      microchimerism. We observed that the hyporesponsive recipients tended to have
      higher levels of donor cells in their peripheral blood (> 1:6,000) than did the
      responsive recipients. We previously reported that 22% of kidney recipients had
      developed donor antigen-specific hyporeactivity at 12 to 18 months
      posttransplant. In our current study of 33 kidney recipients, we observed
      peripheral blood allogeneic microchimerism in 7 (21%) at 12 to 18 months
      posttransplant. The level of donor cells was very low (approximately 1:75,000),
      with no correlation between donor antigen-specific hyporeactivity and peripheral
      blood allogeneic microchimerism at the time point tested. These studies emphasize
      the organ-specific nature of the development of donor antigen-specific
      hyporeactivity and the persistence of peripheral blood allogeneic microchimerism.
      Donor antigen-specific hyporeactivity correlates with very low levels of donor
      cells in liver recipients, while a higher critical level of donor cells is
      important in lung recipients. Additional sequential early posttransplant studies
      are necessary to further define the possible interrelationship between donor
      antigen and the development and maintenance of donor antigen-specific
      hyporeactivity.

PMID- 8545887
TI  - Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7
      1dim, B7-2-) induce alloantigen-specific hyporesponsiveness in murine T
      lymphocytes.
AB  - The functional maturation of dendritic cells (DC) and other antigen-presenting
      cells is believed to reflect the upregulation of cell surface major
      histocompatibility complex (MHC) class II and other T cell co-stimulatory
      molecules, especially the CD28 ligands B7-1 (CD80) and B7-2 (CD86). In this
      study, we propagated cells exhibiting characteristics of DC precursors from the
      bone marrow (BM) of B10 mice (H-2b; I-A+) in response to granulocyte-macrophage
      colony stimulating factor (GM-CSF). The methods used were similar to those
      employed previously to propagate DC progenitors from normal mouse liver. Cells
      expressing DC lineage markers (NLDC 145+, 33D1+, N418+) harvested from 8-10-day
      GM-CSF stimulated BM cell cultures were CD45+, heat-stable antigen+, CD54+,
      CD44+, MHC class II+, B7-1dim but B7-2- (costimulatory molecule-deficient).
      Supplementation of cultures with interleukin-4 (IL-4) in addition to GM-CSF
      however, resulted in marked upregulation of MHC class II and B7-2 expression.
      These latter cells exhibited potent allostimulatory activity in primary mixed
      leukocyte cultures. In contrast, the cells stimulated with GM-CSF alone were
      relatively weak stimulators and induced alloantigen-specific hyporesponsiveness
      in allogeneic T cells (C3H; H-2k; I-E+) detected upon restimulation in secondary
      MLR. This was associated with blockade of IL-2 production. Reactivity to third
      party stimulators was intact. The hyporesponsiveness induced by the GM-CSF
      stimulated, costimulatory molecule-deficient cells was prevented by incorporation
      of anti-CD28 monoclonal antibody in the primary MLR and was reversed by addition
      of IL-2 to restimulated T cells. The findings show that MHC class II+ B7-2- cells
      with a DC precursor phenotype can induce alloantigen-specific hyporesponsiveness
      in vitro. Under the appropriate conditions, such costimulatory molecule-deficient
      cells could contribute to the induction of donor-specific unresponsiveness in
      vivo.

PMID- 8545889
TI  - Identification of donor-derived dendritic cell progenitors in bone marrow of
      spontaneously tolerant liver allograft recipients.
AB  - Multilineage donor-derived hematopoietic cell chimerism is a persistent feature
      of spontaneously tolerant mouse liver allograft recipients. We have shown
      previously that normal liver-derived precursors of "chimeric" dendritic cells
      (DC) propagated in vitro migrate in vivo to T-dependent areas of allogeneic
      lymphoid tissue, where they or their progeny appear to persist indefinitely. In
      this study, granulocyte-macrophage colony-stimulating factor (GM-CSF)+interleukin
      4 (IL-4) were used to propagate DC progenitors from freshly isolated mouse bone
      marrow. The progenitor cells gave rise in 7-10 days to potent antigen-presenting
      cells (APC) that stimulated naive allogeneic T cells in primary mixed leukocyte
      cultures (MLC). The culture method, together with the reverse transcriptase
      polymerase chain reaction (RT-PCR) for the detection of donor and recipient
      strain major histocompatibility complex (MHC) class II mRNA was used to test
      whether donor-derived DC could be propagated from the bone marrow of unmodified,
      orthotopic liver allograft recipients. Freshly isolated bone marrow from these
      transplanted animals contained small numbers of donor cells and responded to GM
      CSF+IL-4 stimulation. In addition to cells expressing recipient (B10) phenotype
      (H-2Kb+; Iab+), a minor population of donor (B10.BR)-derived cells (H-2Kk+; Iak)
      were also propagated from liver graft recipients euthanized two weeks
      posttransplant. DC sorted from these cultures exhibited stimulatory activity for
      recipient strain T cells consistent with a low level (< 1%) of donor DC
      propagation. The immunologic role of donor-derived DC progenitors in liver
      allograft recipients and its relation to the induction and maintenance of donor
      specific unresponsiveness remains to be determined.

PMID- 8545890
TI  - Acute renal injury in the interferon-gamma gene knockout mouse: effect on
      cytokine gene expression.
AB  - We studied major histocompatibility complex (MHC) and cytokine mRNA induction
      after renal injury in the absence of interferon-gamma (IFN-gamma) using IFN-gamma
      gene knockout (GKO) mice. The left renal pedicle of normal (wild-type) and GKO
      BALB/c mice was clamped for 60 minutes; cytokine and MHC mRNA expression were
      monitored in the injured kidney and compared to the contralateral control kidney.
      After a single episode of ischemic injury, the expression of mRNA for MHC class I
      and II, interleukin-2, interleukin-10, granulocyte-macrophage colony-stimulating
      factor, tumor necrosis factor-alpha, and transforming growth factor-beta 1 was
      increased in wild-type and GKO mice, whereas preproepidermal growth factor
      (ppEGF) was reduced. IFN-gamma expression was induced in wild-type mice but
      absent in the GKO mice. Therefore, local injury was equally effective in both
      wild-type and GKO mice with equivalent cytokine and MHC mRNA induction, proving
      that local tissue injury can induce MHC expression by non-IFN-gamma factors.

PMID- 8545891
TI  - LEW-to-F344 carotid artery allografts: analysis of a rat model of posttransplant
      vascular injury involving cell-mediated and humoral responses.
AB  - A key manifestation of chronic rejection is an obliterative arteriosclerosis.
      Myointimal thickening in the vessel is preceded by an endothelialitis involving
      accumulation of host mononuclear cells in the perivascular and intimal spaces. We
      report a paratopic LEW-to-F344 rat carotid artery transplantation model developed
      to study the cells, cytokines, and inflammatory response associated with this
      early phase of vascular immune injury. Compared with contralateral control
      arteries and isografts, LEW-to-F344 carotid allografts develop intimal thickening
      with mononuclear cell infiltration that persists (days 20, 45, 75, 90, and 120).
      Allografted vessels had dense collections of intimal and adventitial leukocytes
      (CD45+) consisting of equal numbers of T cells and macrophages. There were small
      but variable numbers of intimal smooth muscle cells. Intimal cells showed dense
      staining for tumor necrosis factor-alpha, interleukin-8, platelet-derived growth
      factor, iNOS, and ICAM and weaker labeling for interleukin-1 beta and interleukin
      6. There was also prominent staining for interleukin-4 and interleukin-7 with no
      detectable interferon-gamma or interleukin-2 staining and high titer labeling for
      IgG1 (but not IgG2). The predominance of the T cell infiltrate coupled with
      interleukin-4 and IgG1 expression in carotid allografts is consistent with a TH2
      response. This contrasts with balloon-injured rat carotids, which evoke a
      macrophage-dependent proliferative response. These findings demonstrate that
      there are distinct as well as common activation pathways in various forms of
      vascular injury and the LEW-to-F344 carotid model provides the opportunity to
      gain insight into molecular mechanisms regulating alloimmune injury in the
      vessel.

PMID- 8545892
TI  - Mucosal perfusion and reactivity of the rat small intestinal allograft.
AB  - During acute rejection (AR), the endothelial targeting seen in the mucosal
      vessels of the intestinal allograft (IA) could impair the blood supply and
      response to luminal stimuli. To study the effect of AR in the perfusion and
      reactivity of the IA mucosa, we measured the mucosal blood flow in the ileum (IL)
      of 2 groups of control rats (Lewis and ACI) and in the native and grafted IL of
      syngeneic (ACI to ACI) and allogeneic (donor ACI to recipient Lewis) rats. Using
      reflectance spectrophotometry and laser-Doppler flowmetry, parameters of mucosal
      oxygen saturation (ISO2), hemoglobin content (IHB), and blood flow (FLOW) were
      obtained at baseline and after saline and 50% dextrose (D50) stimulation. When
      compared to controls, the isograft IL had similar perfusion (ISO2, IHB, and
      FLOW). The allograft IL showed ischemia (similar ISO2, and lower ISO2 and FLOW).
      In the allografts, the ISO2 and FLOW were lower than in the isografts. In
      response to D50, the native IL of all groups showed an increased IHB and FLOW
      (hyperemia); the isografts showed an increase only in IHB (partial response); the
      allografts did not show any response at all. In summary, the mucosal perfusion in
      the rejecting allografts, but not in the isografts, showed ischemia. The response
      to D50 seen in the native ilea was only partial in the isografts and absent in
      the allografts. Because these changes occurred before the onset of mucosal
      ulcerations, we postulate that they could be used as early indicators of AR.

PMID- 8545893
TI  - Prevention of functional, structural, and molecular changes of chronic rejection
      of rat renal allografts by a specific macrophage inhibitor.
AB  - Chronic rejection is the primary cause of long-term allograft loss. Macrophages
      and their products have been shown to be critical in the development of this
      process in an established kidney allograft rat model. A new synthetic agent,
      Gamma lactone, is a specific inhibitor of macrophages and monocytes that inhibits
      the generation of these populations in vitro and their activities in the effector
      phase of host alloresponsiveness. We tested its effects on the development of
      chronic changes in the model. Untreated control allograft recipients developed
      increasing proteinuria after 12 weeks; progressive glomerulosclerosis,
      interstitial fibrosis, and arterial obliteration developed thereafter.
      Infiltrating ED1+ macrophages as noted by immunohistology increased dramatically
      between 12 and 16 weeks, localizing preferentially in glomeruli and perivascular
      areas. The presence of these cells was associated with dense expression of their
      products. Reverse transcription polymerase chain reaction confirmed and expanded
      the immunohistological findings, showing significant gene expression of
      macrophage-derived mediators. In contrast, recipients treated with G-Lac daily
      for 32 weeks never developed proteinuria; macrophage infiltration was
      dramatically reduced, and expression of their products was virtually absent. At
      32 weeks, most glomeruli and arteries remained histologically normal. In another
      group in which treatment was stopped at 24 weeks, however, proteinuria began to
      develop by 32 weeks; macrophages infiltrated the organs and expression of their
      products became manifest. These results confirm the importance of macrophages and
      macrophage-derived factors in chronic rejection and suggest that a specific
      inhibitor of macrophage activation may be useful in the prevention of the process
      over the long term.

PMID- 8545894
TI  - Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506.
AB  - To evaluate the roles of extracellular FKBP12, we examined the effect of
      extracellular FKBP12 on the immunosuppressive activity of FK506 in vitro and
      clinically. The ability of FK506 to suppress phytohemagglutinin-induced
      proliferative response of human peripheral blood mononuclear cells was inhibited
      in the presence of recombinant FKBP12 dose-dependently. We measured plasma levels
      of FKBP12 using a newly developed enzyme-linked immunosorbent assay system in 34
      patients receiving FK506 after liver transplantation. In 7 patients with acute
      cellular rejection, plasma FKBP12 increased significantly at the onset of
      rejection compared with 1 week before onset (P < 0.05) and further increased to
      or remained at more than 250 ng/ml 1 week after onset. In 22 of 27 patients
      without acute cellular rejection, plasma FKBP12 was less than 70 ng/ml during the
      4 weeks after transplantation. In the other 5 of 27 patients without acute
      cellular rejection, plasma FKBP12 exceeded 250 ng/ml. Rapid increase of plasma
      FKBP12 was observed in only one of these 5 patients, at the onset of high fever
      due to a liver abscess. There was no significant difference in whole blood trough
      levels of FK506 between the patients with or without acute cellular rejection.
      These results suggest that the rapid increase in plasma levels of FKBP12 may
      contribute to the occurrence and progress of acute cellular rejection probably by
      inhibiting the immunosuppressive activity of FK506.

PMID- 8545895
TI  - Detection of HLA IgG antibodies by two enzyme-linked immunoassays, solubilized
      HLA class I and PRA-STAT. Comparison with the AHG PRA.
AB  - HLA class I-directed IgG antibodies have traditionally been detected with a
      complement-dependent lymphocytotoxicity (CDL) technique. We have evaluated two
      solid-phase enzyme-linked immunoassays (EIA) and compared them with the CDL
      antihuman globulin (AHG) dithiothreitol-treated (DTT) PRA in their ability to
      discriminate between the presence or absence of HLA class I-directed IgG
      antibodies in serum from patients awaiting transplantation. The EIA were: (1) an
      EIA that uses solubilized HLA class I antigens (sHLA-I) isolated from a 240
      member platelet donor pool, and (2) the PRA-STAT ELISA kit. For the first
      comparison, we used 691 serum samples from 272 patients taken before they had
      been transplanted. The data show a significant (P < 0.0001) linear correlation (r
      = 0.77 between the AHG DTT PRA and the sHLA EIA. They also demonstrate that the
      mean sHLA-I EIA ratio significantly increases (P < 0.01) above background levels
      with each stepwise increase in AHG DTT PRA level. Discordant results were 1.0%
      (7/691) for sHLA-I EIA+ PRA- and 6.3% (44/691) for PRA+ sHLA-I EIA-. However, a
      lower correlation was noted between the AHG DTT PRA and the PRA-STAT (Nextran)
      PRA results (n = 230; r = 0.42). The sHLA-I EIA is able to determine whether or
      not HLA Class I IgG antibodies are present in serum from transplant candidates
      and is an appropriate adjunct to the traditional CDL PRA assay, whereas the PRA
      STAT is not.

PMID- 8545896
TI  - Soluble HLA antigens and ELISA--a new technology for crossmatch testing.
AB  - A soluble HLA ELISA for the detection of donor specific anti-HLA class I IgG
      antibodies was developed and compared with microlymphocytotoxicity. Donor sHLA
      was prepared from donor blood or purified blood lymphocytes and captured onto
      monoclonal antibody coated ELISA plates. After incubation of captured HLA with
      test serum, bound IgG antibodies were detected using a peroxidase-conjugated anti
      human IgG antibody. Serum samples from patients on waiting lists to receive
      kidney transplants were tested by lymphocytotoxicity (AHG protocol) and/or sHLA
      ELISA in four different laboratories using HLA preparations from eight organ
      donors. Concordant crossmatch results were obtained for 854 (99%) of 864 ELISA
      crossmatches. In contrast, concordant results were obtained for 234 (91%) of 256
      lymphocytotoxicity crossmatches. Interlaboratory reproducibility of ELISA results
      was 99%. In contrast, interlaboratory reproducibility of lymphocytotoxicity assay
      results was 78%. Endpoint titrations of serum specimens containing anti-HLA
      antibodies demonstrated equivalent sensitivity of ELISA and AHG
      lymphocytotoxicity crossmatch and similar sensitivity of ELISA and flow cytometry
      crossmatch. Specimens tested positive by lymphocytotoxicity without DTT treatment
      but negative with DTT treatment were tested negative by ELISA. Comparison of
      lymphocytotoxicity and ELISA crossmatch results showed an agreement of 94%. This
      demonstrates that detection of anti-donor HLA class I antibodies by ELISA is a
      reliable alternative to microlymphocytotoxicity testing.

PMID- 8545897
TI  - Evaluation of HLA antibodies with the PRA-STAT test. An ELISA test using soluble
      HLA class I molecules.
AB  - HLA-specific antibody, present before or after transplantation, may adversely
      effect graft outcome. Antibody testing by cytotoxicity (CYT) is laborious,
      requires viable lymphocytes, does not differentiate non-HLA cytotoxic antibody,
      and cannot be used readily on specimens from patients being treated with
      cytotoxic antibodies. We have evaluated PRA-STAT, an antibody screening kit that
      uses an ELISA test with soluble HLA class I molecules as targets. We performed
      219 tests on a variety of serum specimens, 128 of which were also tested by CYT.
      There was a highly significant correlation (r = 0.78, P < 0.001) between PRA-STAT
      (PS) and CYT for the detection of IgG antibodies. Of 66 sera reactive in both
      assays, 18% had identical specificities defined in both, 27% were more reactive
      in PS than in CYT, 8% were more reactive in CYT, and 47% had different
      specificities in the 2 assays, with overlap in slightly more than half the cases.
      Of 13 sera reactive only in PS, 2 were from non-transfused, nontransplanted males
      with no evidence of lymphocyte-reactive antibody by antiglobulin tests. PS uses
      an IgG-specific conjugate, therefore IgM class I-specific antibodies cannot be
      identified--however, their presence does affect test outcome. This, as well as
      the panel composition and interlot reproducibility, are areas we believe need to
      be addressed. The PRA-STAT system is rapid, does not require viable cells or
      complement, and can be automated in part. Resolution of the problems identified
      here and availability of an IgM-specific conjugate should make this test system a
      valuable tool in histocompatibility testing.

PMID- 8545898
TI  - Assessment of methylprednisolone pharmacokinetics and cortisol response during
      the early and chronic postrenal transplant periods.

PMID- 8545899
TI  - Long-term (24-month) follow-up of steroid withdrawal in renal allograft
      recipients with posttransplant diabetes mellitus.

PMID- 8545900
TI  - Diurnal variation of cyclosporine clearance in stable renal transplant recipients
      receiving continuous infusion.

PMID- 8545901
TI  - Effect of age, sex, and glomerular filtration rate on renal function outcome of
      living kidney donors.

PMID- 8545902
TI  - Direct evidence for in vivo induction of CD8+ cytotoxic T cells directed to donor
      MHC class I peptides following mouse allotransplantation.
AB  - There is accumulating evidence indicating that the T cell response to donor major
      histocompatibility complex (MHC) peptides plays a crucial role in graft
      rejection. We and others previously demonstrated the involvement of MHC class-II
      restricted recognition of donor MHC class I and II peptides by alloreactive CD4+
      T helper cells in graft rejection. Here we studied the in vivo induction of CD8+
      cytotoxic T lymphocytes (CTL) directed to donor MHC class I peptides following
      allotransplantation in the mouse. To address this question, BALB/c irradiated
      splenocytes (H-2d) (Kd, A(d), E(d), Ld, Dd) were injected into Ld-deficient
      BALB/c-dm2 (dm2) mutant mice (Kd, A(d), E(d), -, Dd). Nine days after allogeneic
      cell transplant, recipient lymph node T cells were tested for cytolytic activity
      using peritoneal macrophages as targets. We observed that in addition to BALB/c
      targets, dm2 macrophages could also be lysed but only when incubated with a
      dominant peptide on donor Ld molecule, Ld 61-80. This response was abolished by
      anti-CD8 but not anti-CD4 monoclonal antibodies. In addition, after immunization
      of dm2 mice with the peptide Ld 61-80, alloreactive CTL were generated in vivo
      and shown to destroy allogeneic donor BALB/c target cells in the absence of
      exogenously added peptide. We conclude that after allotransplantation,
      concomitant in vivo priming of alloreactive CD8+ CTL by donor MHC class I
      peptides occurs through both direct and indirect pathways of allorecognition.

PMID- 8545903
TI  - A faster transduction mechanism for the cochlear amplifier?

PMID- 8545904
TI  - Mapping cognitive brain function with modern high-resolution
      electroencephalography.
AB  - High temporal resolution is necessary to resolve the rapidly changing patterns of
      brain activity that underlie mental function. While electroencephalography (EEG)
      provides temporal resolution in the millisecond range, which would seem to make
      it an ideal complement to other imaging modalities, traditional EEG technology
      and practice provides insufficient spatial detail to identify relationships
      between brain electrical events and structures and functions that are visualized
      by magnetic resonance imaging (MRI) or positron emission tomography (PET). Recent
      advances overcome this problem by recording EEGs from more electrodes, by
      registering EEG data with anatomical information from each subject's MRI, and by
      correcting the distortion that is caused by volume conduction of EEG signals
      through the skull and scalp. Along with its ability to record how brains think
      when performing everyday activities in the real world, these advances make modern
      EEG an invaluable complement to other functional neuroimaging modalities.

PMID- 8545905
TI  - Two new genes for Alzheimer's disease.

PMID- 8545906
TI  - Theory meets experiment: correlated neural activity helps determine ocular
      dominance column periodicity.
AB  - The development of ocular dominance columns in primary visual cortex has
      attracted much interest from both experimentalists and theoreticians. One key
      parameter of these columns is their periodicity - it is thus important to
      understand how this is determined. Novel experimental work demonstrates that the
      periodicity is influenced by the temporal patterning of afferent activity, as
      predicted by recent theoretical work.

PMID- 8545907
TI  - Trinucleotide-repeat expansions and neurodegenerative diseases.

PMID- 8545908
TI  - Do adrenergic chromaffin cells exocytose like noradrenergic cells?

PMID- 8545909
TI  - Do muscle-spindle afferents act as interneurons during mastication?

PMID- 8545910
TI  - Modular organization of motor behavior in the frog's spinal cord.
AB  - The complex issue of translating the planning of arm movements into muscle forces
      is discussed in relation to the recent discovery of structures in the spinal
      cord. These structures contain circuitry that, when activated, produce precisely
      balanced contractions in groups of muscles. These synergistic contractions
      generate forces that direct the limb toward an equilibrium point in space.
      Remarkably, the force outputs, produced by activating different spinal-cord
      structures, sum vectorially. This vectorial combination of motor outputs might be
      a mechanism for producing a vast repertoire of motor behaviors in a simple
      manner.

PMID- 8545911
TI  - Selective neuronal vulnerability in the hippocampus--a role for gene expression?
AB  - Proposed mechanisms of neurodegeneration focus generally on the triggering of
      toxic biochemical pathways by an increased intracellular concentration of Ca2+.
      Recent evidence also suggests that Ca2+ causes transcriptional activation of so
      called 'cell-death genes'. Efforts to elucidate the basis of selective
      vulnerability have relied on animal models of delayed neuronal death in the
      hippocampus. Biochemical and morphological data indicate that delayed neuronal
      death is a form of programmed cell death, or apoptosis. Observations that
      specific genes are activated transcriptionally for prolonged times in neuronal
      populations that are undergoing delayed death suggest that active gene expression
      is part of the neuronal-death cascade. Although a direct causal role remains to
      be proven, evidence implicates certain genes in neuronal-death pathways.

PMID- 8545912
TI  - Receptive-field dynamics in the central visual pathways.
AB  - Neurons in the central visual pathways process visual images within a localized
      region of space, and a restricted epoch of time. Although the receptive field
      (RF) of a visually responsive neuron is inherently a spatiotemporal entity, most
      studies have focused exclusively on spatial aspects of RF structure. Recently,
      however, the application of sophisticated RF-mapping techniques has enabled
      neurophysiologists to characterize RFs in the joint domain of space and time.
      Studies that use these techniques have revealed that neurons in the
      geniculostriate pathway exhibit striking RF dynamics. For a majority of cells,
      the spatial structure of the RF changes as a function of time; thus, these RFs
      can be characterized adequately only in the space-time domain. In this review,
      the spatiotemporal RF structure of neurons in the lateral geniculate nucleus and
      primary visual cortex is discussed.

PMID- 8545913
TI  - Spinal and bulbar muscular atrophy: a trinucleotide-repeat expansion
      neurodegenerative disease.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset motor
      neuronopathy that is caused by expansion of a trinucleotide (CAG) repeat in the
      androgen-receptor gene. The length of this repeat varies as it is passed down
      through SBMA families, and correlates inversely with the age of onset of the
      disease. The motor-neuron degeneration that occurs in this disease is probably
      caused by a toxic gain of function in the androgen-receptor protein. Subsequent
      to the identification of the mutation in SBMA, other inherited neurodegenerative
      diseases have been found to be caused by the expansion of CAG repeats in the
      coding regions of other genes. Because these diseases probably share a common
      pathogenesis, investigation of SBMA might help to determine a general mechanism
      of neuronal degeneration.

PMID- 8545914
TI  - [Audiological service--reorganization with quality improvement].

PMID- 8545915
TI  - [Handling skills and utilization of hearing aids].
AB  - Seven hundred and fifty adult patients possessing hearing aids were interviewed
      with regard to utilization and handling skills. Although 71% were full-time users
      and 18% were part-time users, only 32% could handle their aids competently.
      Inhabitants of the county's major town clearly managed their aids better than
      residents of the remainder of the catchment area, despite the fact that 85% of
      the former group never sought counselling by hearing therapists. It is concluded
      that not only the traditional audiology professions, but also staff from other
      branches of the health and social services should participate more actively in
      the care of the hearing impaired.

PMID- 8545916
TI  - [Molecular biological aspects of pediatrics].

PMID- 8545917
TI  - [The 1995 Nobel Prize in medicine or physiology--awarded Edward B. Lewis,
      Christiane Nusslein-Volhard and Eric Wieschaus].

PMID- 8545918
TI  - [Does Iodine 131 treatment of goiter result in an acute increase of the volume
      and function of the thyroid gland?].
AB  - Many textbooks claim that radioiodine (131I) treatment should be avoided in
      treatment of a goitre with substernal extension, due to fear of acute swelling of
      the gland with resulting respiratory problems. We examined patients with
      multinodular goitre, either nontoxic (n = 20) or toxic (n = 10) after treatment
      with 131I. An ultrasonically determined thyroid volume and thyroid function
      variables were investigated before and two, seven, 14, 21, 28 and 35 days after
      treatment. In nontoxic goitres the thyroid volume did not increase significantly,
      the maximum increase in the median volume being 4% on day 7. Serum levels of free
      T3 and free T4 indices increased by 20% (day 7) and 13% (day 14) (p = 0.002),
      respectively. Likewise thyroid volume in toxic nodular goitre did not change
      significantly after 131I treatment. None of the patients presented symptoms of
      tracheal compression. We conclude that 131I treatment of nontoxic as well as
      toxic multinodular goitre does not seem to increase thyroid volume.

PMID- 8545919
TI  - [Child psychiatric intervention in connection with district psychiatry. A 2-year
      experimental project with child psychiatric consultation].
AB  - The aim of the study was to describe the requirement for child psychiatric
      intervention in children of psychiatric patients treated within community
      psychiatry and to test the possibilities for intervention in practice. The study
      was carried out in a community psychiatric centre in Copenhagen, to which a child
      psychiatrist was associated as a consultant for two years. Assessment of known
      risk factors for child psychiatric illness was carried out in the families of all
      patients admitted to the centre who had children aged 0-14 years. Intervention
      was systematically carried out and described. The project was evaluated in a
      survey among the staff of the centre. Sixty-five patients, of which the majority
      were women, and 86 children were evaluated. The most frequent diagnoses were
      psychosis and personality disorder. More than half of the children were less than
      three years old. Fourteen children had no contact with their ill parent and 13
      were placed in care. Ten families were referred to child psychiatric treatment.
      Primary intervention was carried out in six cases. A questionnaire among the
      members of the psychiatric staff showed that the project was well accepted and
      considered to be of great profit to the patients and their children. We conclude
      that a high frequency of risk factors for child psychiatric illness were
      identified in families of patients in community psychiatry. The community
      psychiatric setting made preventive intervention possible at a time where no such
      measures otherwise would have been taken. It is therefore recommended that child
      psychiatrists are integrated in community psychiatry as consultants.

PMID- 8545920
TI  - [Streptococcus bovis as the cause of combined endocarditis of the aortic, mitral
      and tricuspid valves].
AB  - A case of combined endocarditis of the aortic-, mitral- and tricuspid valves in
      an otherwise healthy cattle farmer is described. The infective agent was
      Streptococcus bovis. The relation between S. bovis infection and endocarditis is
      discussed.

PMID- 8545922
TI  - [Kaposi sarcoma: another virus-associated neoplasm].

PMID- 8545921
TI  - [Pneumococcal tricuspid valve endocarditis].
AB  - Endocarditis caused by pneumococci is a rare disease and cases that only affect
      the tricuspid valve represent less than 1% of all cases of endocarditis. A case
      presenting with a primary pneumonia and septicaemia is described. Due to
      persistent fever and the occurrence of a cardiac murmur echocardiography was done
      and demonstrated vegetations on the tricuspid valve. The course was complicated
      with septic pulmonary emboli before the patient recovered. Endocarditis with
      pneumococci may occur as a complication to a primary pneumonia and
      underestimation of the frequency with which it occurs is a possibility. Attention
      should be paid to patients with a primary pneumonia who do not respond to the
      initial treatment and to those who after an initial response show recurrent
      fever.

PMID- 8545923
TI  - [Research evaluation].

PMID- 8545924
TI  - [Heart arrest in and out of hospital].

PMID- 8545925
TI  - [Hepatitis A vaccine].

PMID- 8545926
TI  - [Multiple sclerosis--better prognosis].

PMID- 8545927
TI  - [Survival in disseminated sclerosis in Denmark. A nation-wide study of the period
      1948-1986].
AB  - We estimated survival probability and excess death rates for patients with
      multiple sclerosis (MS) on the basis of data from the Danish Multiple Sclerosis
      Registry, which includes virtually all patients diagnosed with MS in Denmark
      since 1948. We reviewed and reclassified all case records according to
      standardized diagnostic criteria. By linkage to the Danish Central Population
      Registry and the National Registry of Causes of Death complete follow-up of all
      MS patients was achieved, with the exception of 25 patients who had emigrated. A
      total of 2300 of the 6727 MS patients included in the study had died before the
      onset of the disease was 28 years in men (compared with 40 years in the matched
      general male population) and 33 years in women (versus 46 years). The excess
      death rate between onset and follow-up (observed deaths per 1000 person-year
      minus the expected number of deaths in a matched general population) was 14.3 in
      men, which was significantly higher than in women (12.0). Excess mortality
      increased with age at onset of MS in people of each sex. The 10-year excess death
      rate has decreased significantly in recent decades. Excess mortality was highest
      in cases with cerebellar symptoms at onset.

PMID- 8545928
TI  - [Hypertensive crises. 1. Pathogenesis and symptomatology].
AB  - Hypertensive crisis is a medical emergency presenting with a severely increased
      blood pressure. The condition is associated with a state of increased
      vasoconstriction, coexisting hyponatriaemia and hypovolaemia. Besides the
      absolute level of blood pressure evidence of organ damage is also important in
      initial judgement of the case. Hypertensive crises are most commonly seen in
      younger patients with essential hypertension and in patients with secondary
      hypertension. It is unknown why a patient with hypertension suddenly develops a
      hypertensive crisis, but the renin-angiotension system seems to play an important
      role. Untreated, the disease will lead to irreversible end-organ damage.
      Hypertensive crises may be divided into "hypertensive emergencies" with evidence
      of severe new and/or progressive end-organ damage, requiring careful reduction of
      blood pressure within an hour, and "hypertensive urgencies" with no evidence of
      end-organ damage or complications where reduction of blood pressure to a safe
      level must be achieved within a few hours.

PMID- 8545929
TI  - [Hypertensive crises. 2. Treatment].
AB  - Hypertensive crisis is a rare condition with increased blood pressure and
      evidence of new or progressive severe end-organ damage. The patients should be
      admitted to hospital, and the blood pressure reduced gradually. Blood pressure
      should not be normalized, but a reduction in mean arterial pressure of 20-25% or
      to a diastolic blood pressure > 100-110 mmHg should be achieved. Patients at
      particular risk for further complications are elderly, patients with
      hypovolaemia, renal insufficiency, ischaemic heart disease and patients with
      neurological deficits. The ideal antihypertensive drug for any form of
      hypertensive crisis does not exist. If the patient can cooperate with oral
      treatment, nifedipine may be used, usually administered as capsules of 10 mg
      orally, producing a rapid and safe reduction in blood pressure of 25% within 10
      15 minutes with a maximal action after 30-60 minutes. The dose may be repeated
      after 30 minutes in case of insufficient blood pressure response. Hypotension is
      rare. Nifedipine in combination with nitroglycerine is of special benefit in
      hypertensive pulmonary oedema. In cases of treatment failure or if the patient
      cannot cooperate with oral treatment, the choice of drug lies between labetalol
      and sodium nitroprusside. Nitroprusside is administered as continuous intravenous
      infusion, the drug is safe to use and is recommended in conditions where
      reduction of blood pressure must be performed with extreme caution such as in
      cases of cerebral infarction and intracranial hemorrhage. Infusion of
      nitroprusside for more than 48-72 hours is inexpedient because the metabolites of
      nitroprusside need monitoring as well. Parenteral drug therapy with labetalol is
      more simple than treatment with nitroprusside, but at the same time somewhat more
      difficult to titrate. Nitroglycerine is very suitable in moderate hypertension
      and ischaemic heart disease, but in severe hypertension with heart disease
      nitroprusside is the treatment of choice. Loop diuretics should not be used as
      first-line drugs, but only in conditions with evidence of volume-overload.
      Patients with hypertensive crisis most often show volume depletion which is
      aggravated by loop diuretics, therefore they should not be used routinely. When
      the blood pressure has been stabilized, an oral antihypertensive drug should be
      started concomitantly to a gradual reduction of the initial parenteral drug
      therapy.

PMID- 8545930
TI  - [Abdominal aortic aneurysm in the county of Viborg. Mortality before and after
      the establishment of a specialized vascular surgery unit].
AB  - In order to analyze the possible benefits on the mortality of abdominal aortic
      aneurysms (AAA) in Viborg county from the establishment of a specialized vascular
      unit in the county, the periods just before (1986-1988) and just after (1989
      1991) the start of the unit were reviewed. Three times as many operations for AAA
      (104/mill/yr) were carried out after the unit opened. Acute operations increased
      sevenfold. In 1986-1988 42 persons experienced rupture of AAA. Twenty-six (63%)
      died outside hospital. Thirteen (32%) died at primary receiving hospitals. Only
      three patients (7%) were operated. One survived, making the overall mortality
      97.5%. The mortality in this period was 187/million persons over 50 years. In
      1989-1991 39 persons experienced rupture. Eleven (28%) died outside hospital.
      Eight (20.5%) died at primary receiving hospitals. One died preoperatively on the
      vascular unit. Nineteen (49%) reached operation, 13 survived (33%) and six
      (15.4%) died postoperatively. The overall mortality was 67%, the mortality of AAA
      was 127/million persons over 50 years. Comparing the two periods, deaths,
      mortality and overall mortality due to ruptured AAA decreased by 32% after the
      introduction of the vascular unit.

PMID- 8545931
TI  - [It is not always necessary to establish a "first aid station" at mass
      gatherings. Cutty Sark Tallships Race 1993].
AB  - Previous studies from outdoor music festivals have recommended medical service
      facilities at first-aid stations. The Cutty Sark Tallships Race was a large
      outdoor event that took place over four days in Esbjerg harbour with about
      500,000 participants and spectators. A total of 68 patients were treated, 28 in
      the first-aid station at the harbour and 40 at the nearby located hospital. The
      disease and injuries presented were not severe. The orthopaedic casualties
      dominated (82%), wounds, contusions and fractures being the most common ones.
      Only seven casualties were related to alcohol abuse. No casualties were related
      to drug abuse. The economic expense was estimated to DKK 14,676. Thus, at outdoor
      mass gatherings of a nature like the Cutty Sark Tallships Race, located near a
      hospital, first-aid stations are not necessary.

PMID- 8545933
TI  - [Pregnancy is a natural phenomenon! What about the risk factors?].

PMID- 8545932
TI  - [Percutaneous removal of an in-situ embolised catheter fragment in a patient with
      Port-A-Cath].
AB  - The totally implantable catheter system has gained popularity as venous access
      when prolonged treatment is needed. It has several advantages over other methods
      of venous access, such as less discomfort for the patient, and a decreased rate
      of complications. A case with an uncommon but potentially serious complication,
      i.e. spontaneous intravascular fracture of the outlet catheter, is reported. The
      distal fragment of the catheter migrated into the right ventricle of the heart.
      The embolized fragment was removed percutaneously with a snare catheter. Causes
      of catheter fracture are discussed, and recommendations for implantation and
      radiological control are outlined.

PMID- 8545934
TI  - [Cerebral involvement in children with birth weight under 1.500 g].

PMID- 8545935
TI  - [Alcoholic ketoacidosis].

PMID- 8545936
TI  - Causes of mortality among sows in Danish pig herds.
AB  - The likely causes of sow mortality in Danish pig herds were investigated in a
      sample of 598 of the breeding animals delivered to a large rendering plant in the
      winter seasons of 1992 and 1993. In 263 cases information about the circumstances
      of the death or euthanasia and the herd characteristics were available, including
      the size of the herd, its health status, the age at weaning, the method of
      feeding and the use of straw for bedding. For these animals the distribution of
      likely causes of death or euthanasia was: leg weakness, 28.5 per cent; problems
      related to farrowing and late pregnancy, 20.9 per cent; disorders of the
      digestive system, 17.1 per cent; disorders of the urinary system, 13.1 per cent;
      physical injuries, 10.7 per cent; and other disorders, 9.5 per cent. For the
      other 335 sows the distribution of likely causes of death was: leg weakness, 16.1
      per cent; problems related to farrowing and late pregnancy, 10.7 per cent;
      disorders of the digestive system, 21.2 per cent; disorders of the urinary
      system, 15.2 per cent; other disorders, 15.0 per cent; and unknown causes of
      death, 21.8 per cent. According to the official statistics from Danish rendering
      plants, more than 60,000 carcases of breeding pigs were processed during 1992,
      corresponding to a mortality rate of 5 to 6 per cent in the sow herds. The
      mortality rate appeared to increase with increasing herd size, and in herds with
      more than 100 sows the mortality rate was three times the mortality in herds with
      fewer than 50 sows. Compared with previous reports, the proportion of disorders
      involving the gastrointestinal system has increased during the past 20 years.
      Gastric dilation is particularly common, probably as a result of the
      intensification of pig production and the associated changes in management
      practises. The use of straw bedding was marginally significant (P = 0.06) and
      associated with a low frequency of gastrointestinal disorders.

PMID- 8545937
TI  - The persistence of the efficacy of injectable or oral moxidectin against
      Teladorsagia, Haemonchus and Trichostrongylus species in experimentally infected
      sheep.
AB  - The persistence of the efficacy of moxidectin was evaluated against experimental
      gastrointestinal nematode infections in 55 lambs randomly allocated to 11 equal
      groups and infected on day 0. Moxidectin 1 per cent injectable solution was
      administered at a dose rate of 0.2 mg moxidectin/kg bodyweight to five of the
      groups on days -42, -35, -28, -21 and -14; five other groups were treated with
      moxidectin 0.1 per cent oral drench at the same dose rate on days -35, -28, -21, 
      14 and -7, and the 11th group remained untreated as a control. The lambs were
      infected experimentally with 8000 Teladorsagia circumcincta, 2000 Haemonchus
      contortus and 10,000 Trichostrongylus colubriformis infective larvae and killed
      three weeks later. Both formulations of moxidectin showed excellent activity
      against T circumcincta and H contortus with almost 100 per cent efficacy against
      the abomasal parasites for up to 35 days after treatment. The efficacy of
      moxidectin 1 per cent injectable against T colubriformis was much higher (> 99
      per cent) than that of the oral drench and it was highly effective up to 21 days
      after treatment, and gave a moderate reduction in worm burden for up to 35 days
      after treatment. No adverse reactions to moxidectin were observed in any of the
      animals.

PMID- 8545939
TI  - A review of post transport mortality among younger calves.

PMID- 8545938
TI  - Glycated blood proteins in canine diabetes mellitus.
AB  - Measurements of serum fructosamine and glycated haemoglobin are increasingly used
      to complement plasma glucose concentration in the fasting dog to diagnose
      diabetes mellitus and to monitor the response to treatment. These measurements
      are not affected by acute changes in the glucose concentration and reflect the
      average plasma glucose concentration over the preceding one to two weeks in the
      case of serum fructosamine and two to three months in the case of glycated
      haemoglobin. Both components can be measured in canine blood samples, but
      glycated haemoglobin is still not measured routinely; however, the serum
      fructosamine concentration can be measured accurately by means of simple
      spectrophotometric assays. The sensitivity and specificity of serum fructosamine
      in diagnosing diabetes mellitus in dogs with clinical signs of the disease are
      very high (0.93 and 0.95, respectively). Furthermore, serum fructosamine can be
      used as a reliable screening test to identify diabetic dogs in an average middle
      aged to older hospital population. In addition, serum fructosamine can
      distinguish between hyperglycaemic non-diabetic dogs and hyperglycaemic diabetic
      dogs. Preliminary data suggest that therapy can be safely monitored and regulated
      on the basis of serial measurements of the serum fructosamine concentration in
      diabetic dogs.

PMID- 8545940
TI  - Contribution of the lesser mealworm beetle (Alphitobius diaperinus) to carriage
      of Salmonella enteritidis in poultry.

PMID- 8545941
TI  - Poorly differentiated pancreatic adenocarcinoma in a chicken.

PMID- 8545942
TI  - 24-hour service.

PMID- 8545943
TI  - 24-hour service.

PMID- 8545944
TI  - Docking of puppies' tails.

PMID- 8545945
TI  - Black hair follicular dysplasia.

PMID- 8545946
TI  - Larval nematode infection and diarrhoea in lambs.

PMID- 8545947
TI  - Special issue: Veterinary virology in Australia, the French connection. In honor
      of the 80th birthday of Dr. Eric French. Conference proceedings. Sidney,
      Australia, 9-11 July 1994.

PMID- 8545948
TI  - Veterinary arbovirus vectors in Australia--a retrospective.

PMID- 8545949
TI  - Field trials of ephemeral fever vaccines.
AB  - Various bovine ephemeral fever (BEF) vaccines were tested between 1982 and 1984
      in 24 Queensland herds; neutralising antibody responses were monitored and six of
      the herds were closely observed following natural challenge with ephemeral fever.
      A vaccine regime of two consecutive vaccinations with attenuated virus combined
      with the adjuvant Quil A provided excellent protection against BEF for at least
      12 months, whereas one vaccination with the Quil A vaccine or two vaccinations
      with vaccine containing the adjuvant aluminium hydroxide gel did not provide
      significant protection. Antibody responses were highest for the vaccine
      incorporating Quil A when it was given as two consecutive injections. There was
      an apparent relationship between neutralising antibody response and the level of
      protection.

PMID- 8545951
TI  - Retrospective diagnosis of bluetongue virus in stored frozen and fixed tissue
      samples using PCR.
AB  - Stored frozen (-70 degrees C) and formalin-fixed tissue samples constitute a
      valuable resource for retrospective studies of infectious diseases, or for
      diagnostic investigations. The polymerase chain reaction (PCR) affords an
      accurate and rapid method for detection of viral nucleic acids. It was applied to
      stored tissue samples collected from sheep inoculated with two Australian
      serotypes of bluetongue virus, BTV 1 and 23, and two North American serotypes,
      BTV 11 and 17. Specific nested PCR products were detected in both frozen and
      formalin-fixed samples from the Australian sheep after storage for 3.5 years. The
      tissues from sheep inoculated with the North American serotypes yielded specific
      nested PCR products after storage at -70 degrees C for 14 years. No specific
      primary PCR products were detected in any frozen or formalin-fixed samples. The
      PCR assay offers a potential benefit for epidemiological studies, and for
      screening of stored semen, embryos and tissue banks.

PMID- 8545950
TI  - Studies on the pathogenesis of bovine ephemeral fever. IV: A comparison with the
      inflammatory events in milk fever of cattle.
AB  - The study of ephemeral fever in cattle has defined a range of haematological and
      biochemical changes in blood which are characteristic of an inflammatory
      response. One of the clinical signs of ephemeral fever, a temporary paralysis
      reversible by treatment with calcium borogluconate, is similar to that in milk
      fever (parturient paresis), a disease of multiparous dairy cows. Three separate
      groups of cows were studied. Four multiparous cows were observed and sampled
      repeatedly during calving, three similar cows and one cow calving for the first
      time in a dairy herd were sampled daily before and after calving; and, in other
      dairy herds, seven cows with milk fever were sampled during illness. One of the
      cows under repeated observation during calving developed milk fever. The results
      showed that all the inflammatory indicators in blood were present in the
      multiparous cows at calving and that these were essentially similar to those
      established in ephemeral fever. The similarities in the four cows sampled
      repeatedly during the periparturient period were: a rectal temperature rise of 1
      to 1.2 degrees C; rise in circulating neutrophils to peaks between 5700 and 11200
      l-6; disappearance of eosinophils for 1 day; hypocalcaemia (plasma Ca < 2.0 mM l
      1); fall of plasma zinc to low levels immediately after calving (plasma Zn < 500
      micrograms l-1); fall of inorganic phosphate (plasma P < 0.9 mM l-1); rises in
      copper (plasma Cu > 1000 micrograms l-1) and plasma fibrin to > 8.75 g l-1.
      Plasma glucose peaked at calving between 5.7 and 8.9 mM l-1 then fell to levels
      ranging between 3.4 and 3.8 mM l-1. Plasma iron rose in one cow to 1220
      micrograms l-1, was unchanged in one cow and fell in the other two to 440 and 860
      micrograms l-1 respectively. The three multiparous cows which were sampled daily
      and calved normally showed similar haematological, macro and micromineral changes
      and fibrin response as did the seven milk fever cases. In the periparturient
      period, milk fever cows differed from multiparous cows calving normally, in
      degree but not in kind, of inflammatory response. It is postulated that an
      inflammatory event occurs in the periparturient period of multiparous cows which
      partially accounts for the falls in plasma calcium. This can precipitate a
      paralysis and other hypocalcaemic signs similar to that seen in acute ephemeral
      fever.

PMID- 8545952
TI  - Australian studies on Newcastle disease virus. The French heritage.
AB  - Eric French contributed greatly to the early Australian studies on Newcastle
      disease virus, producing the foundations on which subsequent Australian studies
      were based. In 1964 he conducted the first major serological survey for Newcastle
      disease in the Australian poultry flock, and showed that the pathotypes of the
      virus recognised at that time were not present. After the isolation of strain V4
      in 1966, he initiated some of the first studies on the nature of this stain. In
      particular, he demonstrated the avirulence of this virus, its ability to infect
      chickens when delivered orally with food and its potential utility as a vaccine.
      Subsequent studies by other workers included the development of strain V4 as a
      conventional vaccine and as a vaccine suitable for use in village chickens.

PMID- 8545953
TI  - Australian-Indonesian collaboration in veterinary arbovirology--a review.
AB  - Australian-Indonesian collaboration in veterinary development programs has led to
      significant advances in the study of arboviruses. This paper reviews the
      resulting knowledge of arboviral infections of livestock in Indonesia. The first
      recognized arboviral disease of animals in Indonesia was bovine ephemeral fever.
      Serology indicates that the virus is widespread, as are related rhabdoviruses.
      Local sheep appear resistant to bluetongue disease, but imported sheep have
      suffered mortalities. Bluetongue viral serotypes 1, 7, 9, 12, 21 and 23 have been
      isolated from sentinel cattle; 1, 21 and 23 at widely separate locations.
      Bluetongue serotype 21 has been isolated from Culicoides spp. Serological
      reactors to Akabane virus are widespread, as are reactors to the flavivirus
      group. Japanese encephalitis, isolated from sentinel pigs, is the flavivirus of
      most veterinary importance but the limit of its easterly distribution is unknown.
      Many of the arboviruses present in Indonesia are also present in Australia and
      elsewhere in Asia. Their patterns of mobility among countries in the region are
      largely undescribed, but there are opportunities for further regional
      collaboration.

PMID- 8545954
TI  - Genetically altered herpesviruses as vaccines.
AB  - Herpesviruses are a common and important cause of disease in most domestic
      animals. While many virus diseases have been successfully controlled by
      conventional vaccines, genetically modified vaccines offer distinct advantages.
      They are less virulent, less likely to result in latency and they include
      genotypic and phenotypic markers which allow differentiation of vaccine virus
      from wild-type virus and serological differentiation of vaccinated animals from
      infected animals. These benefits are particularly useful in eradication campaigns
      for herpesvirus diseases such as Aujeszky's disease and infectious bovine
      rhinotracheitis. Neither conventional nor genetically modified vaccines prevent
      super-infection. This is a major problem for diseases such as Marek's disease
      where virulent virus continues to be excreted from vaccinated animals, thus
      contaminating the environment and making control more difficult. To prevent
      infection, new strategies will need to be developed such as transgenic animals
      which are innately resistant.

PMID- 8545955
TI  - Expression of small regions of equine herpesvirus 1 glycoprotein C in Escherichia
      coli.
AB  - A series of truncated equine herpesvirus 1 (EHV1) glycoprotein C (gC) molecules
      was examined for use as serodiagnostic antigens for EHV1 and EHV4. Small regions
      of EHV1 glycoprotein C, an immunodominant EHV1 glycoprotein, were expressed in
      Escherichia coli as glutathione S-transferase (GST) fusion proteins using the
      bacterial expression vector pGEX-2T. Sera obtained from horses, including sera
      from specific-pathogen-free (SPF) foals, following exposure to either EHV1, EHV4
      or both viruses were used. Several of the fusion proteins were shown to encompass
      EHV1 specific epitopes while others encompassed strong, cross-reactive epitopes.
      One clone, termed pEC-3, produced a soluble and stable fusion protein which
      encompassed amino acids 107-275 of EHV1 gC. Strong cross-reactive epitopes on pEC
      3 were localised to a region encompassed by amino acids 137 to approximately 152
      while EHV1 specific epitope(s) were identified downstream of this region, i.e.,
      approximately amino acids 152 to 275. E. coli expressed EHV1 gC polypeptides
      showed clear potential for use as diagnostic reagents for the detection of cross
      reactive and type-specific EHV1 and EHV4 antibodies present in convalescent
      equine sera.

PMID- 8545956
TI  - Characteristics of equine herpesvirus 1 glycoproteins expressed in insect cells.
AB  - A series of recombinant baculoviruses containing genes for glycoproteins C, D, H
      and L of equine herpesvirus 1 (EHV-1) have been constructed, and the EHV-1
      products characterised by gel electrophoresis and immunoblotting. The EHV-1
      glycoproteins expressed in insect cells were similar but not identical in
      apparent sizes to those expressed in EHV-1 infected mammalian cells. Each of the
      EHV-1 products was recognised by convalescent equine sera, indicating that they
      were all targets for an equine immune response. Mice immunised with baculovirus
      expressed EHV-1 gD and gC acquired an enhanced ability to clear challenge EHV-1
      from respiratory tissues, in association with both neutralising antibody and cell
      mediated immune responses.

PMID- 8545957
TI  - High molecular weight polypeptide bands specific for equine herpesvirus 4.
AB  - Serum neutralisation (SN) and immunoblotting were used in attempts to distinguish
      between natural infections with the closely related viruses equine herpesvirus 1
      (EHV-1) and equine herpes-virus 4 (EHV-4). Horse sera (n = 323) collected in 1990
      from studs with no experience of EHV-1 abortions as well as 197 sera collected in
      1992 from studs with a history of EHV-1 abortions were tested by SN. The two
      groups differed in the proportion with measurable EHV-1 antibody, the 1992 group
      being significantly higher. Both groups had high proportions with EHV-4 antibody
      and no serum had antibody to EHV-1 alone. Pools of positive sera were prepared as
      probes in immunoblots. High molecular weight (> 200 kDa) polypeptide bands
      specific for EHV-4 were detected. No bands specific for EHV-1 only were found.
      The specific EHV-4 polypeptides shared some properties with gp2 of EHV-1.

PMID- 8545958
TI  - Recent isolates of Newcastle disease virus in Australia.
AB  - Forty-five recently isolated strains of Newcastle disease virus and the V4
      vaccine strain of Newcastle disease virus were used to infect experimental
      chickens. Neither V4 nor any of the new strains produced detectable clinical
      disease. All the viruses produced an antibody response and spread by contact.
      Some of the newly isolated viruses produced a more rapid serological response
      than V4 virus did. Dual or multiple infections with one of the new strains of
      Newcastle disease virus, infectious bronchitis virus and Escherichia coli did not
      enhance the pathogenicity of any of the agents.

PMID- 8545959
TI  - Isolation of serotype 1 Marek's disease viruses from vaccinated Australian
      flocks.
AB  - Field samples were received for Marek's disease virus (MDV) isolation from
      clinically affected flocks from several regions of Eastern Australia. Lymphocytes
      were fractionated in Ficoll-Paque and passaged once or twice in chicken embryo
      kidney cultures. Serotype-specific virus was detected in infected cultures by
      indirect immunofluorescence with monoclonal antibodies. Serotype 1 MDV was
      isolated from 10 flocks. In samples from 5 of these flocks, serotype 2 and 3
      vaccine viruses were isolated from the same specimen. In a parallel study,
      plasmas obtained during lymphocyte isolation were tested for antibodies to MDVs
      by agar gel precipitin (AGP) tests using serotype 1 and 3 antigen extracts. No
      correlation was observed between the rate of virus isolation and AGP positivity.
      The AGP test was incapable of discriminating between the different MDV serotypes.

PMID- 8545960
TI  - Molecular evolution of infectious laryngotracheitis virus (ILTV; gallid
      herpesvirus 1): an ancient example of the Alphaherpesviridae?
AB  - An analysis of two essential genes of infectious laryngotracheitis virus (ILTV),
      glycoprotein D (gD) and the immediate early gene, herpes simplex virus homologue
      ICP27, was performed with the equivalent gene homologues from several
      alphaherpesviruses. Amino acid (aa) sequence analysis revealed that these ILTV
      genes shared limited homology to other alphaherpesvirus equivalents and were
      distinct from the two other avian herpesviruses, Marek's disease virus (MDV) and
      herpesvirus of turkeys (HVT). Simplex and varicella group viruses are clearly
      separate from the avian group. The amino acid sequences of these ILTV genes will
      be presented with comparisons to the homologues from other alphaherpes viruses,
      contributing further evidence of the evolution of this group of viruses from a
      common progenitor and that ILTV could be an ancient example of the
      Alphaherpesvirinae.

PMID- 8545961
TI  - The pathologist in virology.
AB  - While the study of a virus may be the domain of a virologist or molecular
      biologist, an understanding of the pattern and dynamics of a viral disease in the
      animal requires a multidisciplinary attack by a team that includes a pathologist.
      This balance is particularly needed in the field where natural disease can be
      subject to influential variables such as duration of infection, immune status of
      the population and the presence of intercurrent infectious agents that may be
      latent or superimposed. Complicating agents vary widely from region to region,
      e.g. Africa compared with South-east Asia. Accurate diagnosis of a field outbreak
      may therefore be difficult in the absence of a full battery of diagnostic tools.
      The design of investigations is critical to the proper interpretation of
      findings.

PMID- 8545962
TI  - Virology before and after HIV.
AB  - The career of Eric French epitomised the pre-HIV era of virology, combining
      active research, effective administration and scholarship. The pressures of AIDS
      funding and the concept of strictly controlled, and narrowly focussed, mission
      oriented research threaten the viability of independent research and may retard
      progress even in those fields which receive the greatest direct support.

PMID- 8545963
TI  - Recent advances in the understanding of Jembrana disease.
AB  - Jembrana disease is a severe and acute clinical disease in Bali (Bos javanicus)
      cattle with a case fatality rate of about 20%, and a mild sometimes subclinical
      disease in other cattle types and buffalo. The aetiological agent has been
      identified as a lentivirus, designated as Jembrana disease virus (JDV).
      Preliminary sequence analysis has confirmed the identity of JDV as a lentivirus
      and has shown that it is distinguishable from BIV. There is antigenic cross
      reactivity between the capsid protein of JDV and the previously identified bovine
      lentivirus designated bovine immunodeficiency virus (BIV). Serological tests that
      detect antibody to the capsid protein of JDV or BIV would not differentiate
      between antibody due to infection by either virus. The diseases induced by BIV
      and JDV infection in cattle are very different, and the pathogenesis of JDV
      infection in Bali cattle is unusual for a lentivirus infection.

PMID- 8545964
TI  - Feline immunodeficiency virus replicates in salivary gland ductular epithelium
      during the initial phase of infection.
AB  - Feline immunodeficiency virus (FIV) antigen was detected by immunochemistry in
      salivary glands of cats experimentally inoculated with West Australian isolate
      T91. Six cats were inoculated subcutaneously with 1.0 ml of tissue culture
      supernatant fluid from a feline T-lymphoblastoid cell line (MYA-1) infected with
      T91. FIV antigens were detected in the interlobular ducts of the salivary gland
      of cats infected with FIV 2, 4 and 6 weeks previously. FIV antigen was not
      detected in the salivary glands of three FIV negative cats and one naturally
      infected cat. Further, FIV antigen was located only in interlobular duct
      epithelial cells. The distribution of FIV in the interlobular ducts confirms the
      important role of salivary glands as a major reservoir of FIV in the early phase
      of infection and strengthens suggestions that the salivary route is an important
      mode of transmission of FIV.

PMID- 8545965
TI  - Elimination of fox rabies from Belgium using a recombinant vaccinia-rabies
      vaccine: an update.
AB  - To improve both safety and stability of the vaccines used in the field to
      vaccinate foxes against rabies by the oral route, a recombinant vaccinia virus,
      expressing the glycoprotein of rabies virus (VVTGgRAB) has been developed.
      VVTGgRAB innocuity was verified in target species and in domestic animals as well
      as in numerous wild animal species that could compete with the red fox in
      consuming vaccine baits in Europe. Oral immunization of foxes, by distributing
      VVTGgRAB vaccine-baits, was undertaken in the whole of the infected area of
      Belgium (10,000 km2). Five campaigns of fox vaccination covering the whole
      infected area were carried out from the autumn of 1989 until 1991. Each time,
      150,000 vaccine-baits were dispersed by air at a mean density of 15 per km2.
      These campaigns induced a drastic decrease in the incidence of rabies and the
      elimination of the disease from 80% of the initial infected area. Regarding the
      geographical evolution of rabies in Belgium and in adjacent regions in
      neighbouring countries, new spatial strategies for bait dispersal were planned
      for 1992, 1993 and 1994: successive restricted campaigns were carried out along
      political borders only. These campaigns induced a new decrease of incidence; no
      rabid foxes could be detected in 1993 in spite of an improved epidemiological
      surveillance. In 1994, rabies was confirmed again in 13 foxes collected in a
      region situated close to the French border. These cases demonstrate the
      persistence of a focus of rabies on the border and justify further restricted
      campaigns of vaccination.

PMID- 8545966
TI  - A probable outbreak of rabies in a group of camels in Niger.
AB  - Seven camels in a herd of approximately 40 camels belonging to nomadic people in
      Niger died over a short period. No diagnostic samples were obtained. Brain was
      obtained from the eighth camel in the group, which died after a clinical illness
      manifested by unusual behaviour, aggression, pica, ptyalism and terminal
      paralysis. Rabies virus was demonstrated in the brain of this camel by
      immunofluorescent staining. Before the deaths of the camels a feral dog had
      joined the nomadic encampment and died there, and a domestic dog belonging to the
      group had then died after displaying aggressive behaviour. It is postulated that
      canine rabies had been transmitted to the camels in the herd.

PMID- 8545967
TI  - Experimentally induced "late-onset" mucosal disease--characterization of the
      cytopathogenic viruses isolated.
AB  - Antigenic and genetic analyses were performed in order to establish relationships
      between the noncytopathogenic (ncp) and the cytopathogenic (cp) bovine viral
      diarrhoea viruses (BVDV) involved in the induction of a case of experimentally
      induced "late-onset" mucosal disease (MD) symptoms. The persistent ncpBVDV, the
      cpBVDV used for superinfection (strain TGAC) and the virus isolates from faeces
      (cpX) were examined using an immunoplaque test (IPT) to distinguish between cp
      and ncp virus populations. The cp populations were cloned by plaque purification
      and found to be free of ncpBVDV when using the IPT. The cpBVDV clones and the
      persistent ncpBVDV were analysed in an enzyme immunoassay on heat-fixed infected
      cells (IM-EIA) and in a neutralization test using a panel of 27 monoclonal
      antibodies against the E0 (gp48) and E2 (gp53) viral glycoproteins. It was found
      that strain TGAC contained two antigenically distinct subpopulations of cpBVDV
      (TGAC-B1 and TGAC-B2). The endogenous ncpBVDV and the cpX clones had the same
      reactivity pattern in both tests. In addition, p80 gene duplications in the
      genomes of the cpBVDV clones were analysed using the polymerase chain reaction
      and subsequent restriction enzyme analysis of the amplicons. The clones analysed
      from TGAC-B1 and those from cpX had gene duplications of identical sizes showing
      the same restriction enzyme patterns. Our results suggest that the cpBVDV which
      finally lead to "late-onset" MD arose by recombination and/or by mutations of the
      cpBVDV used for superinfection.

PMID- 8545968
TI  - Approaches to food-based vaccines for domestic chickens.
AB  - Domestic chickens were fed viral vaccines that were applied to the surface of
      food pellets. Responses were judged by the production of specific antibodies, and
      compared with the responses obtained when the same vaccines were given by
      conventional routes. Chickens responded similarly to commercial avian infectious
      encephalomyelitis vaccine given on food or by eyedrop when antibodies were
      measured by ELISA, and the vaccine virus spread by contact. Increasing the dose
      of oral vaccine tenfold gave a more rapid serological response but the levels of
      antibody were not increased. There was no serological response to commercial
      infectious laryngotracheitis virus vaccine given on food. An experimental avian
      adenovirus vaccine produced a serological response when given on food, but higher
      levels of antibody were produced in response to vaccination by eyedrop. The
      vaccine virus spread by contact. It was concluded that current avian infectious
      encephalomyelitis vaccines, and prospective recombinant vaccines based on avian
      adenovirus vectors, could be delivered on food.

PMID- 8545969
TI  - Faecal viruses of dogs--an electron microscope study.
AB  - Faecal samples from 112 dogs both with and without diarrhoea were screened for
      parvovirus by a haemagglutination titration test and then examined by electron
      microscopy for the presence of viruses and virus-like particles. On the basis of
      morphology eight distinct viruses or virus-like particles were identified.
      Particles identified were coronaviruses, coronavirus-like particles, rotavirus
      like particles, papovavirus-like particles, torovirus-like particles,
      picornavirus-like particles, 27 nm virus-like particles with projections and
      parvovirus-like particles which did not cause haemagglutination.

PMID- 8545970
TI  - ICNV 1966 to ICTV 1994: the contribution of veterinary virology.

PMID- 8545971
TI  - Shedding of "virus-like" particles in canine faeces.
AB  - Diarrhoeic faeces from about 500 dogs were examined by negative stain electron
      microscopy. As well as parvovirus, and some of the other recognised viral causes
      of gastroenteritis, unusual "virus-like" particles were observed in about 8% of
      the samples. The particles were spherical, 100 nm to 300 nm in diameter, and
      surrounded by a thick wall penetrated by numerous pores. An additional 74 samples
      of normal faeces yielded no "virus-like" particles. We do not know the nature of
      these particles.

PMID- 8545972
TI  - An antigen detection immunoassay for big liver and spleen disease agent.
AB  - An enzyme-linked immunosorbent assay (ELISA) able to detect an antigen associated
      with infection with big liver and spleen (BLS) agent was developed. The assay is
      a capture ELISA (C-ELISA) procedure using ELISA plates coated with mouse
      monoclonal antibody (mAb 1H4) for antigen capture and a polyclonal chicken Ig
      preparation, extracted from yolk of BLS antibody positive birds, for detection of
      captured BLS antigen. mAb 1H4 was produced to a partially purified antigen
      preparation from liver suspensions of naturally BLS infected birds. The C-ELISA
      was evaluated for specificity and sensitivity in naturally and experimentally BLS
      infected and uninfected broiler and layer breeds of domestic fowl.

PMID- 8545973
TI  - Comparison of native and subunit antigens as ELISA reagents for the detection of
      antibodies against scabby mouth virus.
AB  - A simple ELISA test to detect antibodies against scabby mouth virus (SMV) has
      been developed. Native whole virions and subunits of SMV generated by boiling the
      virus in the presence of sodium dodecyl sulphate (SDS) detergent and beta
      mercaptoethanol were compared as ELISA assay reagents using naive and hyperimmune
      sera from sheep and rabbits. Approximately 2 x 10(4) intact virus particles per
      microtiter well were required to generate a positive to negative signal of
      0.8:0.3 ELISA O.D. units when the serum was used at a dilution of 1/100. In
      contrast, total subunit antigen generated by disrupting and coupling of 250-500
      virions per well provided a signal ratio of 1.58:0.3 ELISA O.D. units at a serum
      dilution of 1/250. Total subunit antigens were therefore 400 times more
      economical to use than intact virions. In addition, subunit antigens could be
      readily bound to microtiter plates without the need for removal of the SDS.
      Secondly, it was not necessary to block non-specific binding sites on the plate
      with blockers such as gelatin and skim-milk, thereby shortening the time needed
      to complete the ELISA assay. The total subunit antigen ELISA test was used to
      detect seroconversion in new born lambs where there was an occurrence of SMV
      infection in housed sheep. Three bleeds were taken at fortnightly intervals and
      the ELISA results showed that 9 out of 15 lambs were seropositive for all bleed
      points. Four of the lambs showed a sequential rise in titer while only one lamb
      failed to seroconvert.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8545974
TI  - Molecular studies on avian strains of Pasteurella multocida in Australia.
AB  - A collection of 45 strains of Pasteurella multocida was assembled. The strains
      had been isolated from cases of fowl cholera in eastern Australia over 8 years,
      and included mainly type A strains. All the strains were examined for plasmids
      and resistance to 10 antimicrobial agents and most of the strains were examined
      for restriction fragment length polymorphism. Nine strains were assayed for
      pathogenicity for mice. Twenty strains yielded no plasmid. Seven contained a
      single plasmid of 1.3 kbp and 18 contained 2 plasmids, of 2.4 and 7.5 kbp. All
      the strains were resistant to streptomycin, trimethoprim and lincomycin while one
      strain was resistant to tetracycline. There was no correlation between plasmid
      content and resistance to antimicrobial agents. Three strains that lacked
      plasmids were highly virulent for mice, 6 strains containing plasmids were not.
      Restriction fragment length polymorphism generated by HpaII allowed the 39
      strains that were tested to be divided into 10 groups.

PMID- 8545975
TI  - The European Society for Veterinary Virology (ESVV).

PMID- 8545976
TI  - Cell-mediated immunity in chickens vaccinated with the V4 strain of Newcastle
      disease virus.
AB  - A leukocyte migration inhibition assay was used to demonstrate antigen-specific
      cell-mediated immunity (CMI) in chickens vaccinated with the V4 strain of
      Newcastle disease virus. Chickens were vaccinated when 5 weeks old, and again 3
      and 7 weeks later. CMI was detected 9 days after initial vaccination by eyedrop,
      but only after the second dose of vaccine delivered into the crop. In some
      chickens there was a temporary suppression of CMI to Newcastle disease virus,
      especially after the initial application of vaccine to the crop.
      Haemagglutination inhibition antibodies developed to similar levels in chickens
      after vaccination by either route. There was no obvious correlation between
      antibody and CMI responsiveness.

PMID- 8545977
TI  - Receptors for the V4 strain of Newcastle disease virus in the digestive tract of
      chickens.
AB  - Enterocytes were detached from various parts of the digestive tract of chickens
      by treatment with DTT or with hyaluronidase. Isolated enterocytes were exposed to
      suspensions of the V4 strain of Newcastle disease virus (NDV). Removal of virus
      from the supernatant fluid was taken as evidence of binding of virus to
      enterocytes and residual virus was measured both by infectivity assay and by
      ELISA. Enterocytes from duodenum, jejunum, ileum, caecum, and rectum bound the
      virus; enterocytes from oesophagus, crop and proventriculus did not.

PMID- 8545978
TI  - Lactose pellets--a new approach to oral vaccination of village chickens against
      Newcastle disease.
AB  - Newcastle disease in village chickens in developing countries can now be
      controlled with vaccines containing thermostable, avirulent V4 virus delivered on
      food. Logistical problems arise because 7 to 10 g of food vaccine must be allowed
      for each chicken. Lactose-based pellets have been prepared that contain an
      immunizing dose of V4 virus in a single pellet, even after long periods of
      storage. Protective levels of antibody were generated in chickens fed individual
      pellets, or in groups of chickens fed vaccine pellets mixed with normal food.
      Chickens receiving vaccine pellets developed a level of protection against
      challenge with virulent Newcastle disease virus similar to that achieved with
      vaccine added to food. This process when refined will allow the preparation of
      vaccine in regional laboratories and delivery without refrigeration to villages.

PMID- 8545979
TI  - The contribution of lectins to the interaction between oral Newcastle disease
      vaccine and grains.
AB  - Successful oral vaccination of chickens with Newcastle disease (ND) depends on
      the survival of vaccine virus on the grains that are used as carriers. Some
      interactions between grains and the V4 strain of ND virus (NDV) were studied.
      Crude saline washings were prepared from several grains - rice (unhusked, brown,
      white and boiled white), sorghum, millet, wheat, maize and barley - and tested
      for lectin activity, as indicated by agglutination of chicken erythrocytes. Only
      washings from unhusked rice, sorghum and millet failed to haemagglutinate. None
      of the crude washings antagonised the haemagglutinating activity of NDV, and the
      washing from white rice produced an 8-fold enhancement. The presence of lectins
      in the washings from rice, wheat and barley was confirmed by purifying a
      substance with N-acetyl-D-glucosamine specificity. Only the crude extract from
      white rice had any profound effect on infectivity, reducing the infectivity titre
      by 99.99%. It is not known if the viricidal substance is identical with the
      lectin. Of 9 commercial lectins tested, only ConA bound the V4 virus.

PMID- 8545980
TI  - The influence of adjuvants on oral vaccination of chickens against Newcastle
      disease.
AB  - Living V4 strain Newcastle disease vaccine was given to chickens orally. The
      inclusion of DEAE-dextran, Quil-A or TiterMax in the vaccine, or delivering the
      vaccine as Iscoms, did not enhance the serological response. The immediate
      serological response to living V4 vaccine was enhanced in the presence of
      Avridine. Chickens produced a low serological response to oral administration of
      inactivated V4 vaccine. This response was not enhanced in the presence of
      Avridine.

PMID- 8545981
TI  - Mucosal immunity in chickens vaccinated with the V4 strain of Newcastle disease
      virus.
AB  - Chickens vaccinated orally with the V4 strain of Newcastle disease virus (NDV)
      and possessing low levels or undetectable levels of serum haemagglutination
      inhibition (HI) antibodies against NDV may resist challenge with virulent virus.
      Evidence for vaccine-induced mucosal immunity was sought. HI antibodies were
      detected in serum, lachrymal fluid and tracheal washing after vaccination with V4
      virus by intranasal, eyedrop or intracrop routes. IgA was detected by
      immunodiffusion in lachrymal fluid of both vaccinated and control birds. Lymphoid
      accumulations were detected in tracheas of chickens after vaccination and there
      were significant increases in the numbers of plasma cells in sections of
      Harderian glands from chickens after vaccination. In a second experiment, ELISA
      was used to demonstrate the production of NDV-specific IgA which was detected in
      serum, lachrymal fluid, tracheal washing and intestinal washing after intracrop
      or eyedrop vaccination with V4 virus. It was concluded that oral vaccination of
      chickens with V4 virus induces a mucosal immune response.

PMID- 8545982
TI  - Australian X disease, Murray Valley encephalitis and the French connection.
AB  - Epidemics of a severe encephalitis occurred in eastern Australia between 1917 and
      1925, in which over 280 cases were reported with a fatality rate of 68%. The
      disease had not been described previously and was called Australian X disease.
      The next epidemic occurred in south-east Australia in the summer of 1950-51. The
      disease was given its name of Murray Valley encephalitis as this was the area
      from which most cases were reported. A virus was isolated by Eric French in
      Victoria, and about the same time by John Miles and colleagues in South
      Australia. The virus Murray Valley encephalitis (MVE) virus, was shown to be a
      Group B arbovirus (flavivirus) which was related to, but distinct from, Japanese
      encephalitis virus. Early seroepidemiological studies showed that the most likely
      vertebrate hosts were water birds. MVE virus was first isolated from Culex
      annulirostris mosquitoes in 1960. The most recent epidemic of Murray Valley
      encephalitis occurred in 1974, at which time it was renamed Australian
      encephalitis. Since 1974, however, all cases have been confined to northern
      Australia, particularly the north of Western Australia. Indeed, the Kimberley
      region of Western Australia contains the only confirmed enzootic foci of virus
      activity. A closely related flavivirus, Kunjin virus, has also been shown to be
      an aetiological agent of Australian encephalitis. Since the first isolation of
      MVE and Kunjin viruses, considerable information has been accumulated on their
      ecology and epidemiology, some aspects of which are briefly described.

PMID- 8545983
TI  - Influences of vector biology on transmission of arboviruses and outbreaks of
      disease: the Culicoides brevitarsis model.
AB  - The use of a model to appraise arboviral epizootics is described, and examples
      are given which demonstrated long-distance wind-dispersal of the biting-midge
      vector Culicoides brevitarsis from the same endemic source. Vector abundance is
      characterised by peaks and troughs of abundance, the patterns of which vary
      between localities and annually. Short term climatic effects can change rapidly
      the age structure of a population, thus increasing the number of midges that can
      transmit a virus and profoundly influencing the probabilities of viral
      transmission. The population dynamics of vector and viral foci are complex, if
      not chaotic.

PMID- 8545984
TI  - [Evaluation of physical fitness in military personnel using the 1600 meter
      running test].
AB  - Validity of 1600 m running test in estimation of physical fitness of Yugoslav
      Army personnel was examined through the degree of correspondence between the
      results achieved in the test and the values of maximum oxygen consumption. The
      coefficients of linear correlation between these two indices are not
      statistically significant, and amount to -0.36 (in 87 cadets) and -0.14 (in 114
      officers). The authors conclude that 1600 m running test is not a valid measure
      of endurance, as an element of physical fitness of military personnel and they
      elaborate the reasons of its unreliability.

PMID- 8545985
TI  - [Reconstructive surgery of the colon and rectum following war injuries].
AB  - The results were presented of the retrospective analysis of the treatment of 116
      patients' with colostomies following war injuries. Reconstructive operations were
      performed on these patients between November 1 1991 and November 1 1994.
      Operations were performed on 8 patients with caecostomy, 47 with
      transversocolostomy, 45 with colostomy on the descendant and sigmoid colon and on
      16 patients with Hartmann procedure. The average age of patients was 33.77 years.
      The occlusion of colostomy was performed in 81 patients, and in 19 of them the
      resection with T-T anastomosis was done with difficulties due to technical
      problems caused by adhesions, ventral hernias, defects of mesenterium and
      abdominal wall. Occlusion was also performed in 16 patients with Hartmann
      procedure. The complications encountered were: ileus in three patients, stercoral
      fistula in 3 (healed with conservative therapy), dehiscence of anastomosis in 1
      patient (cured after reoperation, exteriorization of both ends of colon), and
      wound infections in 21 patients. There was no lethal outcomes.

PMID- 8545986
TI  - [Peripheral nerve injuries during the 1991-1993 war period].
AB  - In the period 1991 - 1993, 931 casualties with 1435 injured peripheral nerves
      were surgically treated at the Clinic for Neurosurgery of the Military Medical
      Academy. The statistical analyses of these series was done according to the type
      of the injured nerves, the age and sex of the wounded. The cause of injuries,
      associated and combined injuries, distribution of single and multiple lesions of
      certain nerves, as well as employed surgical procedures were analyzed.

PMID- 8545987
TI  - [Etiology and incidence of amaurosis in war injuries of the eye].
AB  - Retrospective analysis of the medical documentation of 506 wounded treated at the
      Ophtalmological Clinic of the Military Medical Academy, was used to separate the
      cases where, due to the injury, the eyesight was destroyed or reduced to "the
      sense and projection of the light". The groups were formed according to the
      mechanism of injury and etiological factor. In 41.03% of eyes described sight
      impairment was established on admission, and the perforative injury of the eye
      was the basic etiological factor in 64.26% of the cases.

PMID- 8545988
TI  - [Maternal mortality in central Serbia].
AB  - This paper described the trend of official maternal mortality rate in Serbia
      excluding provinces for the last 30 years and it was investigated whether it was
      underregistered. Data for calculation of the official rate of maternal mortality
      were obtained from the publications of the official health statistics. Five
      hundred and three death certificates of women in reproductive period, that died
      in the period May-December 1992 in central Serbia, were examined to investigate
      underregistration. Notable decrease of the official rate of maternal mortality
      found in the period of 30 years, could be the basis for satisfaction if the
      results of investigation did not suggest that the significant number of maternal
      deaths was underregistered.

PMID- 8545989
TI  - [Treatment of patients with subfulminant forms of viral hepatitis B using
      prostaglandin E1].
AB  - The efficacy of prostaglandin E1 was demonstrated in the treatment of 4 patients
      with subfulminant hepatitis caused by a virus B. Three patients suffered from
      hepatic enchepalopathy of the first degree, and the remaining one of the second
      degree. In three patients the clinical and biochemical improvement came
      relatively quickly, followed by recovery. In one patient, due to drug
      intolerance, the treatment was discontinued on the third day. The recurrence of
      illness was noted with the moderate increase of serum aminotransferases
      activities without clinical deterioration, necessitating no further use of
      prostaglandin E1. Prostaglandin E1, applied in the treatment of patients with
      subfulminant form of hepatitis, has favorable effect on the course of illness.

PMID- 8545990
TI  - [Fibrin glue--an effective hemostatic-adhesive system].

PMID- 8545991
TI  - [Principles of surgical treatment of war injuries of the peripheral nerves].

PMID- 8545992
TI  - [Causalgia in the light of new findings].

PMID- 8545993
TI  - [Control and quality assurance in radiotherapy].

PMID- 8545994
TI  - [Focal cerebral ischemia in a patient with mitral valve prolapse and an atrial
      septum anomaly].

PMID- 8545995
TI  - [Pyoderma gangrenosum associated with Crohn's disease].

PMID- 8545996
TI  - [Recurrent intrahepatic cholestasis in pregnancy].

PMID- 8545997
TI  - Agents that cause birth defects.

PMID- 8545998
TI  - Sensory evoked potential and effect of SS-cream in premature ejaculation.
AB  - The cause of premature ejaculation (PE) has been thought to be psychological in
      the majority of patients but we investigated penile hypersensitivity for an
      organic basis of PE. For another organic basis of PE, we have suggested
      hyperexcitability of the ejaculation center. SS-cream is a topical agent
      containing 9 oriental herbs for treating PE. Clinically SS-cream has been
      effective in the treatment of PE. Therefore, in order to implicate the organic
      basis of PE and realize the effect of SS-cream on PE, we investigated the
      somatosensory evoked potential (SEP) in patients with PE(16 cases) and the
      effects of SS-cream on SEP for treating PE. The latencies and amplitudes of the
      evoked responses were measured by two different places in stimuli, one was on the
      penile shaft with ring electrode and the other on the glans penis with a surface
      electrode. The latency of SEP stimulated at the glans penis was significantly
      longer than that stimulated at the penile shaft (p < 0.05). The latency
      stimulated at the glans penis after applying SS-cream was significantly longer
      than before applying SS-cream (p < 0.05), which was near the level of a normal
      potent man. But the latency stimulated at the penile shaft has no significant
      difference between before and after the application of SS-cream (P > 0.05). The
      amplitudes of the evoked responses stimulated at the glans penis were
      significantly higher than those stimulated at penile shaft (p < 0.05). And both
      these amplitudes were significantly reduced with the application of SS-cream (p <
      0.05). With these result, we can suggest that the patients with PE have glans
      penile hyperexcitability and it provides further implications for an organic
      basis of PE, SEP stimulated at the glans penis can be a very useful method to
      evaluate PE, along with SEP stimulated a penile shaft and SS-cream prolongs the
      sensory conduction and reduces the penile hyperexcitability of the patient with
      PE.

PMID- 8545999
TI  - Relationship of change in body mass to blood pressure among children in Korea and
      black and white children in the United States.
AB  - Body mass is a major factor in determining blood pressure levels in children. We
      compared associations of body mass with blood pressure in 121 white and 91 black
      children in Bogalusa, Louisiana with that of 370 children in Kangwha, Korea. All
      children were seven years old at entry into the study and were followed for three
      years. Korean children were shorter (p < 0.001) thinner (p <0.0001), and had a
      lower body mass index (p < 0.01) than white or black children. At age seven,
      systolic blood pressure levels were 2 approximately 5 mm Hg lower, but at age 10,
      they were 2 approximately 5 mm Hg higher in Korean than white or black children.
      The increases in blood pressure levels from age seven to ten years were much
      greater in Korean than black or white children, while changes in height, weight,
      and body mass index were generally less. Change in blood pressure level was
      positively associated with change in body mass index for systolic (but not
      diastolic) levels; however, the association was no stronger for Korean than for
      U.S. children, except for Korean males vs Bogalusa black males. Cross-cultural
      studies of other factors, such as diet and physical activity, may explain these
      differences.

PMID- 8546000
TI  - Role of human papillomavirus and p53 tumor suppressor gene in cervical
      carcinogenesis.
AB  - To determine whether the dysfunction of p53 protein, caused either by the
      mutation of p53 gene itself or by the human papillomavirus (HPVs) is involved in
      the development of cervical cancers and to find out the status of p53 tumor
      suppressor gene in HPV positive or negative cancers, we analyzed 64 cases of
      primary cervix cancers. First, polymerase chain reaction (PCR) was performed with
      E6 consensus primer pairs to detect the infection of HPVs in cervix cancer
      tissues. Second, to screen the p53 gene mutation, PCR of p53 exon 5 through 9 and
      single strand conformation polymorphism (SSCP) analysis were performed with p53
      exon specific primers. Finally, overexpression of p53 protein was checked by
      immunohistochemical staining with anti p53 antibody. We found HPVs in 43 cases
      out of 64 cases (67.2%). HPV type 16 was positive in 26 cases, type 18 was
      positive in 7 cases, and 6 cases were positive for both HPV type 16 and 18. HPV
      type 31 or 33 was not detected in our experiments, and in 4 cases, type of HPVs
      were unknown. The SSCP analysis showed mobility shifts in 8 cases (6 in HPV
      positive cases; 2 in HPV negative cases) and the sequence analysis confirmed the
      results of SSCP analysis. In addition, the overexpression suggesting the mutation
      of p53 gene was detected in 27 cases (42.2%, 21 in HPV positive cases; 6 cases in
      HPV negative cases). Our results support the previous reports that the
      dysfunction of p53 plays an important role in the development of cervix cancers
      but contrary to the results obtained from cervix cancer all lines, there is no
      inverse correlation between HPV infections and p53 mutations in primary cervix
      cancers.

PMID- 8546001
TI  - Design of an emergency teleradiology system based on progressive transmission.
AB  - In clinical surgery, there are frequent needs for communication between the house
      staff and the attending physician in an emergency situation. To overcome the
      limitation of voice communication through the telephone line, we have designed an
      'emergency teleradiology system' which can be used for emergency surgical and
      medical decision making. This system can transmit the high quality images of CT,
      MRI, and other X-ray data using a PC attached to a modem through the conventional
      telephone line. It is based on the progressive transmission system which enables
      the successive update of a received image. The iterative residual coding/decoding
      algorithm efficiently compresses the image to maximally utilize the low bandwidth
      PSTN channels. This system also satisfies design requirements such as low-cost,
      ease of operation, fast transmission, and interactive image communication
      including voice. Test results using several CT, MR, and X-ray images evaluate the
      compression performance, image quality, transmission time and computational time
      of the coding and decoding processes, thus demonstrate the usefulness of this
      system in an emergency situation.

PMID- 8546002
TI  - Cytogenetic study employing chorionic villi in ectopic pregnancy.
AB  - Maternal factors such as salpingitis and peritubal adhesion are known to be
      associated with ectopic pregnancy; however, a few studies have considered the
      chromosomal complements of ectopic conceptuses. We studied 16 ectopic conceptuses
      obtained by surgical resection. The karyotyping of chorionic villi was performed
      using direct and culture technique. Among 16 studied cases, 14 cases showed
      normal karyotype (nine with 46, XY; five with 46, XX). One case showed trisomy
      16(47, XY, + 16) and another showed variation from normal chromosomal complement
      (46, XY, 14s+), resulting in 6.3% incidence of the structural abnormalities of
      the chromosome. On the basis of our study, we determined the possibility of
      chorionic villi karyotyping in ectopic pregnancy. This ectopic conceptuses are no
      more likely to show chromosomal abnormalities than in utero conceptuses of
      comparable gestational age. Therefore, maternal factors such as salpingitis and
      peritubal adhesion are the most likely explanations for ectopic pregnancy.

PMID- 8546003
TI  - Clinical significance of serum TSH in euthyroid patients with paroxysmal atrial
      fibrillation.
AB  - Atrial fibrillation may occur in patients with a variety of cardiovascular or
      chronic disease as well as in normal subjects. Many authors reported that atrial
      fibrillation occurs in patients with thyrotoxicosis. It is reported that a low
      serum thyrotrophin concentration in an asymptomatic person with normal serum
      thyroid hormone concentrations can be a independent risk factor for developing
      atrial fibrillation. But we focused on the significance of serum thyroid
      stimulating hormone (TSH) in the euthyroid patient with atrial fibrillation whose
      serum level of T3, T4, fT4, and even TSH were absolutely within normal range. On
      our results, there was no significant differences in age, sexual distribution,
      and left ventricular ejection fraction between the patients group of paroxysmal
      and chronic persistent atrial fibrillation (p > 0.05), but there was larger left
      atrial dimension (LAD) and more cases of rheumatic heart disease in the chronic
      persistent atrial fibrillation group and there was more cases of lone atrial
      fibrillation in the paroxysmal atrial fibrillation group (p < 0.05). There was no
      significant differences in serum levels of T3, T4, fT4 between paroxysmal and
      chronic persistent atrial fibrillation, but significantly lower serum TSH was
      found in patients with paroxysmal atrial fibrillation (p < 0.001), and these
      findings were more significant after the control of hemodynamic change (p < 0.001
      vs p < 0.05). The discriminant value in serum TSH between the paroxysmal and
      chronic atrial fibrillation group was 1.568U/mL with about 76% of predictive
      power. There was significantly lower serum TSH in paroxysmal atrial fibrillation
      in all age groups (p < 0.05). There was a significantly higher prevalence of
      cerebral thromboembolic events in chronic persistent (27.7%) and disease
      associated (15.0% atrial fibrillation than in the paroxysmal (3.3%) and lone
      (4.5%) atrial fibrillation group (p < 0.001). Therefore, we suggest that serum
      TSH below the serum concentration of 1.5U/mL can be a risk factor for developing
      atrial fibrillation when the serum level of T3, T4, fT4, and even TSH were within
      absolutely normal range.

PMID- 8546004
TI  - Detection of antibodies to human melanoma cell in vitiligo by western blot
      analysis.
AB  - Vitiligo is a disease in which melanocytes are selectively destroyed. The disease
      is thought to be an autoimmune process being there are antibodies to pigment
      cells in the sera of patients and animals with vitiligo. In the present study,
      sera from vitiligo patients were examined for reactivity with the human melanoma
      cell line, SK-Mel-28, by Western blot analysis of solubilized membrane antigens
      of these cells to identify the pigment cell antigens defined by antibodies in the
      patients with vitiligo. Antibody reactivity to human melanoma cells (SK-Mel-28)
      was investigated in 14 patients with vitiligo, and 16 with normal control
      individuals. Antibodies to the 116-113, 60, 40 KD antigens were associated with
      vitiligo being present in 79%, 86%, and 43% respectively of the patients with
      vitiligo, but in only 6%, 38% and 6% of the normal controls. In contrast,
      antibodies to the 160-155, 78 and 64 KD antigens were equally common in vitiligo
      and in normal individuals. The results suggest that autoreactivity to pigment
      cells occurs more commonly in patients with vitiligo than in the normal control
      and high autoreactivity to pigment cells in the vitiligo sera might be an
      impertinent epiphemenon to destroyed pigment cell.

PMID- 8546005
TI  - Percutaneous transluminal coronary angioplasty for ostial stenosis of the left
      coronary artery--a case report and literature review.
AB  - A 11-year-old girl developed left main coronary artery osteal stenosis after
      Takayasu's arteritis for which she underwent Percutaneous Transluminal Coronary
      Angioplasty (PTCA). The narrowing of the left coronary artery was successfully
      dilated by angioplasty without apparent complication. This one suggests that PTCA
      may have a potential advantage as a temporary method to postpone the
      aortocoronary bypass surgery in a child with coronary artery stenosis due to
      Takayasu's arteritis.

PMID- 8546006
TI  - Hypertrophic neuropathy with complete conduction block-- hereditary motor and
      sensory neuropathy type III.
AB  - Hypertrophic neuropathy is a non-specific consequence of repeated demyelination
      and remyelination, encountered in a wide range of inherited and acquired
      disorders. We report an 11-year-old boy with HMSN III, a kind of hypertrophic
      neuropathy, with clinical, electrophysiologic and pathologic data. The
      electrophysiologic studies show complete conduction block in the upper and lower
      extremities with severe abnormal spontaneous activities. The pathologic findings
      of sural nerve reveal prominent hypomyelination, onion bulb formation, and severe
      endoneurial collagenization. Complete conduction block with the preservation of
      fair to good grade muscle strength is an unusual finding in hypertrophic
      neuropathy and other peripheral neuropathies, in general.

PMID- 8546007
TI  - Antibody recognition of picornaviruses and escape from neutralization: a
      structural view.
AB  - Escape of picornaviruses from neutralization by monoclonal antibodies is mediated
      by substitutions of very few, defined amino acid residues of the capsid,
      generally located on the tip of some surface-exposed loops. Substitutions at the
      same positions are possibly of major relevance to antigenic variation of
      picornaviruses in the field. Such residues tend to cluster in discrete areas,
      termed antigenic sites. The structure of virus-antibody and peptide-antibody
      complexes, determined by cryoelectron microscopy and X-ray crystallography,
      combined with studies using site-directed mutagenesis, are beginning to reveal
      new features of picornavirus epitopes. This information complements and expands
      the view on picornavirus antigenicity previously provided by analyses of antibody
      escape mutants. In addition to amino acids found replaced in escape mutants,
      other surface residues which remain invariant in spite of immune pressure also
      participate in contacts with the antibody molecule. Some invariant residues are
      even critical for the antigen-antibody interaction. Escape mutations occur at the
      subset of antigenically critical residues which are tolerant to change because
      they are not essentially involved in capsid structure or function. Restrictions
      to variation differ among epitopes; this may contribute to explain the different
      number of serotypes among picornaviruses, and the frequency at which
      antigenically highly divergent variants occur in the field.

PMID- 8546008
TI  - Genetic variation of wild Puumala viruses within the serotype, local rodent
      populations and individual animal.
AB  - Reverse transcriptase polymerase chain reaction cloning and sequencing were used
      to determine the range of S gene/N protein variability in wild Puumala virus
      (PUU) strains and to study phylogenetic relationships between two groups of
      strains which originated from Finland and from European Russia. Analyses of the
      nucleotide and predicted amino acid sequences showed: (1) all PUU strains shared
      a common ancient ancestor; and (2) the more recent ancestors were different for
      the Finnish branch and the Russian branch of PUU strains. A cluster of amino acid
      substitutions in the N protein of Finnish strains was found; this cluster was
      located within a highly variable region of the molecule carrying B-cell epitopes
      (Vapalahti et al., J. Med. Virol., 1995, in press). Different levels of S gene/N
      protein diversity of PUU were revealed supporting the view of geographical
      clustering of genetic variants. Puumala virus from individual voles was found to
      be a complex mixture of closely related variants-quasispecies. The ratio of non
      silent to silent nucleotide mutations registered in the S genes/N proteins of PUU
      quasispecies was 4- to 16-fold higher than that in Puumala virus strains,
      resulting in a more wide range of quasispecies N protein sequence diversity.

PMID- 8546009
TI  - Identification of Kk-restricted T-cell epitope within influenza virus
      nucleoprotein.
AB  - In order to determine the epitope structure in peptide NP50-63, which has been
      reported to be the only Kk-restricted T-cell antigen within the influenza virus
      (A/PR/8/34) nucleoprotein, a series of 13 peptides truncated from C- and N
      termini of NP50-63 were synthesized and their sensitizing activities against Kk
      restricted nucleoprotein-specific cytotoxic T lymphocytes (CTLs) were examined.
      One of the 13 peptides, NP50-57, sensitized L929 cells at the nM level, which was
      100-1000 times lower in concentration than that at which the other peptides
      sensitized these cells. The presence of NP50-57 in A/PR/8/34-infected L929 cells
      was also investigated. Acid extracts of virus-infected cells were separated on a
      reverse-phase HPLC column and then anion-exchange column. By both separations,
      only one peak of sensitizing activity against nucleoprotein-specific CTLs was
      observed. The position of the peak coincided with that of the elution of NP50-57.
      These results strongly suggest that NP50-57 is the natural epitope in the
      antigenic structure, NP50-63.

PMID- 8546010
TI  - DNA sequence of the simian varicella virus (SVV) gH gene and analysis of the SVV
      and varicella zoster virus gH transcripts.
AB  - The varicella zoster virus (VZV) glycoprotein H (gH) stimulates VZV-specific
      immune responses and may be involved in virus penetration. This study reports the
      genomic map position and the DNA sequence of a simian varicella virus (SVV)
      homologue of the VZV gH gene. A 32P-labeled VZV gH-specific DNA probe hybridized
      to the HindIII B subclone of the SVV BamHI B restriction endonuclease (RE)
      fragment. The DNA sequence of the SVV HindIII B subclone was determined and
      analysis indicated a SVV open reading frame (ORF) homologous to several
      herpesvirus gH genes. The SVV gH ORF is 2559 base pairs in size and encodes a 852
      amino acid protein. The SVV gH contains characteristics of a transmembrane
      glycoprotein including: 9 consensus N-linked glycosylation sites, a potential
      amino terminal signal sequence, and a predicted transmembrane segment located
      near the carboxyl terminus. The SVV and VZV gH genes exhibit 60.0% identity and
      the predicted polypeptides exhibit 54.5% identity. The SVV and VZV gH transcripts
      were analyzed and the promoter regions were compared. 32P-labeled SVV and VZV gH
      specific DNA probes each hybridized to a single 2.9 kilobase transcript. The mRNA
      start sites of the SVV and VZV gH genes were determined by primer extension
      analysis, and alignment of the promoter regions indicated similar content and
      arrangement. The extensive conservation of SVV and VZV genes and predicted
      polypeptides further supports the use of SVV infection of non-human primates as a
      model of VZV infection of humans.

PMID- 8546011
TI  - Human adenovirus serotype 3 (Ad3) and the Ad3 fiber protein bind to a 130-kDa
      membrane protein on HeLa cells.
AB  - The fiber protein of adenovirus mediates the interaction of adenovirus with cell
      membrane receptors. We have produced the Ad3 fiber protein in the baculovirus
      expression system. Biochemical, morphological and functional analyses showed that
      the recombinant fiber was properly folded and functionally competent. The
      specific binding of Ad3 virus to two HeLa membrane proteins of 130 and 100 kDa
      was demonstrated with an overlay protein binding assay. In the same assay, Ad3
      fiber only recognized the 130-kDa protein. Divalent cations seemed to be
      important for the interaction of both virus and fiber with these proteins.

PMID- 8546012
TI  - Cloning and sequencing of a 8.4-kb region from the 3'-end of a Taiwanese virulent
      isolate of the coronavirus transmissible gastroenteritis virus.
AB  - The nucleotide sequence (8396 nucleotides) was determined, from the 3'-end of the
      putative polymerase gene to the poly(A) tail, for a Taiwanese virulent isolate,
      TFI, of transmissible gastroenteritis virus (TGEV). The TFI nucleotide sequence
      had very high identity to the British virulent field isolate FS772/70 (98.3%),
      the attenuated Purdue 115 (96.7%) and from the S gene to ORF-4 gene region, to
      the low passaged virulent Miller (98.3%) strains of TGEV. Comparison of the TFI S
      protein sequence with those determined from other TGEV strains and those of the
      TGEV variant, porcine respiratory coronavirus, isolated from Europe and North
      America showed that they had changed very little over a period of 4 decades. The
      two extra amino acids found to be present in the spike proteins of the virulent
      FS772/70 and Miller strains when compared to the avirulent Purdue strain were
      found to be present in the TFI strain. The genomic organisation of the TFI strain
      was the same as that of the other TGEV viruses.

PMID- 8546013
TI  - [Molecular biological research on the origin of the angiosperms].
AB  - Nucleotide sequence of 23S-5S chloroplast rDNA spacer region including 4.5S rRNA
      gene of several dozens of seed plants was determined. The data obtained were used
      to construct phylogenetic trees and to compare them with the analogous data from
      literature. Topologies of trees constructed for various types of macromolecules
      and by different methods demonstrate obvious similarities although they are not
      identical. Some clue stages of seed plants evolution still remain obscure.
      Critical analysis of all the available information allows to come to several more
      or less definite conclusions. All the data say that angiosperms are a
      monophyletic group which diversified far before their fossils are definitely
      registered, i.e., before lower Cretaceous. Ancestral angiosperms were not
      genealogicaly related to modern woody Magnoliales but were represented by
      "paleoherbs", i. e. herbaceous and semiherbaceous magnoliids and monocots.
      Monocots originated at the earliest stages of angiosperms evolution and are not,
      probably, monophyletic. Woody Magnoliales and eudicots with tricolpate pollen
      seem to appear later in evolution. The conclusion that Gnetales is a sister group
      to angiosperms does not find enough support in molecular studies. Summing up, it
      looks as if a long period of existence of angiophytes preceded the pre-Cretaceous
      angiosperms irradiation. This line of development originated simultaneously with
      phylogenetic lineages of modern gymnosperms.

PMID- 8546014
TI  - [The relationship of the lifespan of eukaryotes (animals and plants) to their
      physical characteristics].
AB  - Over a wide range of living species from rotifer to sequoia it was shown that
      there is positive correlation between species longevity and linear size (r =
      0.93, n = 186), as well as between species longevity and mass (r = 0.94, n = 37).
      Real slope of correlation line longevity on mass may be near 0.27. So, for all
      studied species exist the general low- the more its mass (or weight, or volume),
      the longer its life span. It is possible that between mass (or volume) and
      longevity of living things there is causal relation.

PMID- 8546015
TI  - [Amino acid chemoreception and motor activity in the frog Rana lessonae
      (Amphibia)].
AB  - The changes motor activity in the frog Rana lessonae in clean water depends on
      the type amino acids, stimulating chemoreceptors. Reactions orientations (as
      reaction of recognizing) in adult frog are caused by only amino acids constantly
      present in ponds water, while amino acids, only periodically appearing in ponds
      water, are not caused. Amino acids with more short chains of carbon atoms in the
      molecules (C3-C4) are more effective (with significance p < 0.01) in change motor
      activity, than amino acids with more long chains (C5-C6) of the molecules. This
      law is characteristic (on literature by data) for reactions of taste receptors in
      fishes. It is possible that chemoreceptors of Rana lessonae, perceiving amino
      acids and initiating changes in behavior this animal, resembles the taste
      receptors in fishes.

PMID- 8546016
TI  - Susceptibility of poultry lactobacilli to ionophore antibiotics.
AB  - The susceptibility of four poultry Lactobacillus strains to monensin, narasin,
      lasalocid, salinomycin and maduramicin was investigated using two different
      systems of lactobacilli cultivation. In the MRS broth (Oxoid) with glucose, the
      growth of lactobacilli was inhibited at ionophore concentrations as low as 0.4-5
      microgram/ml. On the other hand, the growth of lactobacilli in the mixture of a
      commercial concentrate with water (1:2) was not influenced by ionophores at 100
      micrograms/g. It follows from these results that lactobacilli are much more
      resistant to ionophores in their natural environment than in laboratory cultures
      on glucose. It was concluded that: probiotic lactobacilli can be added to
      ionophore-containing concentrates; antibiotic susceptibility data obtained in
      liquid cultures with glucose are misleading.

PMID- 8546017
TI  - Detection of antibodies to rabbit haemorrhagic disease virus: an immunoblotting
      method using virus-coated human erythrocyte membranes.
AB  - The virus of rabbit haemorrhagic disease (RHDV) was purified from infected rabbit
      liver homogenate by using its property to bind to human red blood cells. Lysates
      from virus coated cells contained a 60 kDa protein identified as the major viral
      protein. Immunoblots prepared with that preparation were proved to be useful for
      immunochemical analysis since the 60 kDa component was intensively stained by
      subsequent incubation with rabbit sera from infected rabbits and with a secondary
      labelled antibody. The sera from 114 rabbits were analysed with this test and the
      data were compared with those obtained by using the haemagglutination inhibition
      test (HIT). Among the 114 field sera tested by Western blot, 86 contained
      antibodies to the 60 kDa RHDV antigen whereas only 76 showed positive reaction by
      HIT. The sensitivity and the specificity of the Western blot were 0.85 and 0.45,
      respectively, with a concordance between the two techniques of 0.72.
      Additionally, the European brown hare syndrome virus antibodies reacted with the
      60 kDa RHDV protein on immunoblots.

PMID- 8546018
TI  - Cerebral coeneurosis in chamois (Rupicapra pyrenaica).
AB  - Two cases of cerebral coeneurosis in chamois (Rupicapra pyrenaica) from Catalonia
      (northeastern Spain) are described. This disease, of which few cases have been
      reported, may, in fact, be relatively frequent. Although the characteristic
      symptom of the disease in sheep is circling, that symptom was not observed in
      this study. Chamois may act as a host within the sheep-shepherd-dog cycle, but is
      probable that red fox (Vulpes vulpes) also acts as a definitive host.

PMID- 8546019
TI  - Pattern of infection with the porcine reproductive and respiratory syndrome virus
      on swine farms in Belgium.
AB  - On four closed breeding-fattening farms, 17 sows and their litters were examined
      for porcine reproductive and respiratory syndrome virus (PRRSV) antibodies in the
      blocking enzyme-linked immunosorbent assay (ELISA). On each farm, the pigs were
      born within the same week and remained together for 12 weeks. The pigs were
      followed serologically to determine the antibody profile with the purpose of
      establishing the infection pattern of PRRSV. A total of 13 sows had antibodies
      and a positive correlation existed between their titre and the maternal antibody
      titre of their litters at 2 weeks of age. The maternal antibodies were detectable
      until 4-10 weeks of age. On two farms, no infection occurred during the time of
      the experiment as no seroconversion was observed in the eight litters. On the two
      other farms, infection was observed in eight of the nine litters between 4 and 12
      weeks of age while one litter became infected during the fattening period. In
      some litters, a few pigs seroconverted between 6 and 8 weeks, others between 8
      and 10 weeks and still others between 10 and 12 weeks. This observation indicated
      a rather slow spreading pattern of PRRSV. At the time of entry on four commercial
      fattening farms, which is 10-11 weeks of age, 15%, 50%, 75% and 60%,
      respectively, of the pigs had antibodies to PRRSV. Based on the rate of decline
      of maternal antibodies as determined by the studies on the closed breeding
      fattening farms, it was indicated that these positive pigs had already been
      infected on the farm of origin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8546020
TI  - Isolation and characterization of paramyxoviruses from snakes and their
      relationship to avian paramyxoviruses.
AB  - Several viruses were isolated from snakes which died during an outbreak of
      disease in a zoo. The viruses could be cultivated at 28 degrees C on a snake cell
      line (VH2, ATCC CCL 140). In cell culture they formed syncytia, leading to
      destruction of the monolayer. The isolates were sensitive to treatment with
      chloroform but not to growth in the presence of IUDR and revealed
      haemagglutinating activity with chicken erythrocytes. These results, combined
      with electron microscopic examination of the infectious supernatant, confirmed
      the diagnosis of paramyxoviruses (PMV). Haemagglutination inhibition tests with
      antisera against avian PMV revealed a serological relationship between the snake
      viruses and the avian PMV serotypes 1 and 7. Tests for thermostability at 56
      degrees C showed a marked decrease of the haemagglutination and infectivity
      titres in contrast to the avian PMV serotype 7. The multiplication of the snake
      viruses seemed to be restricted to incubation temperatures below 37 degrees C. At
      28 degrees C the snake viruses could be cultivated in several cell cultures.
      Separation of virus proteins using polyacrylamide gel electrophoresis showed
      differences between the snake isolates and avian PMVs of serotypes 1 and 7.

PMID- 8546021
TI  - A retrospective study of bovine abortions associated with Bacillus licheniformis.
AB  - A retrospective study of bovine abortions associated with Bacillus licheniformis
      is described. The material consisted of 2445 bovine abortions submitted for
      diagnostics from 1986 through 1993. Initially, B. licheniformis had been isolated
      from 81 cases. Sections of these cases were re-examined microscopically and
      immunohistochemically by a PAP technique using a primary antibody against B.
      licheniformis. Of these abortions, 47 were most likely associated with B.
      licheniformis as tissue lesions with immunostained bacteria were present in
      these. In the remaining cases the diagnosis may not have been established due to
      the lack of sufficient materials, or the isolation of the bacterium was
      considered to be a result of contamination. In four cases concomitant infections
      with B. licheniformis and bovine virus diarrhoea virus were present. Abortions
      caused by B. licheniformis were predominantly seen during the winter months and
      in late pregnancy. The most common lesions were necrotizing placentitis followed
      by fetal multifocal suppurative bronchopneumonia. Immunohistochemically, B.
      licheniformis was demonstrated in association with tissue lesions and
      intracellularly in trophoblasts. The pattern of bacterial isolations, especially
      from the placenta, lungs, and abomasal contents, combined with the histological
      findings points to B. licheniformis abortions as being of haematogenous origin
      with subsequent transplacental spread to the fetus.

PMID- 8546022
TI  - Evaluation of mebendazole activity on experimental murine toxocariasis by immune
      complexes determination.
AB  - The mebendazole action on experimental murine toxocariasis, using different
      formulations and vehicles, was studied by means of the detection of antibodies
      and immune complexes by ELISA. After inoculation with 1000 embryonated Toxocara
      canis eggs, BALB/c mice were submitted to the anthelmintic treatment as follows:
      group 1 (control without treatment); group 2 (mebendazole (MBZ), Lomper, Steve
      Laboratories, Barcelona, Spain, suspended in 1% sodium carboxymethylcellulose
      (CMC) at a dose of 100 mg/kg/day); group 3 (MBZ, pure compound suspended in 1%
      CMC at a dose of 100 mg/kg/day); group 4 (MBZ, pure compound suspended in water
      at a dose of 100 mg/kg/day); group 5 (MBZ, pure compound, formulated to a solid
      dispersion at 10% in polyethylene glycol 6000 (PEG) then dissolved in water at a
      dose of 100 mg/kg/day); group 6 (MBZ, pure compound, formulated to a solid
      dispersion at 10% in PEG then dissolved in water at a dose of 50 mg/kg/day);
      group 7 (MBZ, pure compound, formulated to a solid dispersion at 10% in PEG then
      dissolved in water at a dose of 25 mg/kg/day). The treatments were administered
      on days 5-7 post-inoculation (p.i.) inclusive. The dynamics of the production of
      the specific antibodies for both excretory-secretory (ES) antigen or crude
      extract showed a similar profile as compared to the control group. In groups 2
      and 6, from the beginning of the treatment, values of immune complexes fell
      rapidly and were undetectable for the remainder of the experiment. Reductions of
      immune complex levels by the 4th-6th, 2nd-3rd and 2nd-5th weeks p.i. were
      observed from groups 3, 5 and 7, respectively. In the other groups, similar
      profiles as compared to the control group were observed in the dynamics of the
      specific immune complexes. The evaluation of chemotherapy by immunological
      methods is a valid technique for the efficiency of the treatment without the
      disadvantages of larval recovery from several digested tissues. Mebendazole, pure
      compound, formulated to a solid dispersion in PEG, then dissolved in water
      reduced immune complexes from the beginning of the treatment. The larval
      immobilization produced by MBZ should entail a reduction in their metabolic
      activity with a reduction in the production of excretory-secretory substances
      which are responsible for the formation of immune complexes. The rapid clearance
      of specific immune complexes together with a total larvae reduction would explain
      the decrease in specific immune complexes, which detection is a valid technique
      for monitoring the efficiency of treatment.

PMID- 8546023
TI  - Experimental infection in mice with Bacillus licheniformis.
AB  - The pathogenicity of Bacillus licheniformis was assessed in normal and
      immunodepressed BALB/c mice. The animals were challenged intravenously with 4 x
      10(7) colony forming units of B. licheniformis (ATCC 14580) and both normal and
      immunodepressed mice were susceptible. However, the infection was more severe in
      the immunosuppressed animals. In normal mice, lesions were restricted to the
      liver and kidneys, while lesions also occurred in other organs of immunodepressed
      mice. By crossed immunoelectrophoresis it was shown that antigens of B.
      licheniformis are potent immunogens, and the bacteria could be identified in
      tissue sections by immunostaining. Immunohistochemically, B. licheniformis was
      demonstrated in hepatic and pulmonic macrophages, and from some animals the
      bacteria were also reisolated.

PMID- 8546024
TI  - Hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle.
AB  - We describe a family line with an autosomal recessive disease of muscular
      dystrophy of the diaphragmatic muscles in Holstein-Friesian cattle.
      Histopathological examination in the present cases revealed various degenerative
      changes in the diaphragmatic and other thoracic muscles as follows: variation in
      muscle fiber diameter, fiber splitting, sarcoplasmic masses, ring fiber, vacuolar
      and hyalinized degeneration of muscle fibers. In addition, central core-like
      structures were the prominent features in the diaphragmatic muscles, occupying
      the center of the fiber or scattered within the fiber. These pathological
      alterations are consistent with the diaphragmatic myopathy previously reported in
      Meuse-Rhine-Yssel cattle in the Netherlands. The fibers containing core-like
      structures consisted of three distinct zones which could be well distinguished by
      NADH-tetrazolium reductase activity. This activity was absent in the innermost
      zone, decreased in the intermediate zone, and normal or increased in the
      periphery. Electron microscopically, this structure appeared to be composed of
      focal myofibrillar degeneration beginning with streaming or disintegration of the
      Z disk. We discuss here the similarity between this core-like structure and the
      other alternative organelles that have been reported previously, and a possible
      defect or storage in the cytoskeleton from the findings of the Z disk
      abnormalities.

PMID- 8546025
TI  - Calcitonin gene-related peptide- and substance P-immunoreactive axons in the
      nucleus gracilis of the rat with special reference to axonal dystrophy: light and
      electron microscopic observations.
AB  - Calcitonin gene-related peptide (CGRP) and substance P (SP)-immunoreactive (IR)
      axons in the nucleus gracilis of normal rats (1-15 months of age) were studied by
      light and electron microscopy. Besides many CGRP-IR and SP-IR varicosities with
      normal appearance, we found a few swollen (nearly round or oval) varicosities
      with either CGRP or SP immunoreactivity. Swollen CGRP-IR varicosities were more
      frequently seen than SP-IR ones, appearing from 3 months of age and increasing in
      number and size (up to approximately 25 microns in diameter) with advancing age.
      At the electron microscopic (EM) level, CGRP-IR and SP-IR swollen varicosities
      showed dystrophic changes, i.e., many membranous dense bodies, and proliferation
      of microtubules and neurofilaments. CGRP-IR or SP-IR dystrophic axons also
      contained many mitochondria and sometimes made synaptic contacts with nonreactive
      dendrites (occasionally with non-IR axons). These findings suggest that the
      dystrophic CGRP and SP axonal profiles represent a functionally distinct
      subpopulation of axonal dystrophy in the nucleus gracilis and use CGRP or SP as a
      neuroactive substance. Using a double-immunostaining method, many of normal CGRP
      IR axons were identified to be SP-IR. However, no single dystrophic varicosity
      was found to contain both CGRP and SP immunoreactivities. These findings suggest
      that CGRP and SP afferents are independently affected and progress to dystrophic
      changes.

PMID- 8546026
TI  - Alzheimer's disease-type neurofibrillary degeneration in verrucose dysplasias of
      the cerebral cortex.
AB  - Verrucose dysplasias, found at autopsy in the cerebral cortex of three elderly
      individuals (two without neurological disorders and one with motor neuron
      disease), are shown to present neurofibrillary degeneration of Alzheimer's
      disease type. This neurofibrillary degeneration immunoreacted with antibodies
      against abnormally phosphorylated tau (5E2 and AT8), disclosed acetyl- and
      butyrylcholinesterase activity, and was consistently stained with thioflavin-S.
      Cortical dysplasias, found either as isolated verrucose nodules or comprising
      multiple nodules, contained cell-sparse areas around which a peak of
      neurofibrillary changes was seen. Cell-sparse areas were sometimes bridged by
      stripes of neurons and fibers arranged in a radial fashion, and many of these
      neurons showed neurofibrillary degeneration. Cytoskeletal abnormalities were
      conspicuous in layers II and III at the external borders of the dysplasias, as
      well as in neurons located in layers V and VI, and in the white matter beneath
      layer VI in central zones of each lesion. The morphology of cells undergoing
      neurofibrillary changes (from early non-fibrillar stages to late extracellular
      ones) suggests that neurons disturbed in their migration toward the site to which
      they had been committed may become vulnerable to cytoskeletal changes. Micro
      environmental disturbances related to hypoxia-ischemia in the affected cortex are
      proposed as likely contributing factors for the long-term production of this
      neurofibrillary degeneration.

PMID- 8546027
TI  - Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy.
AB  - There is controversy as to whether zidovudine (ZDV) induces a mitochondrial
      myopathy that is distinguishable from human immunodeficiency virus (HIV)
      associated myopathy in ZDV-naive patients. Mitochondrial abnormalities were
      evaluated in skeletal muscle obtained from 18 HIV-positive, ZDV-exposed patients,
      and 9 who were drug naive. All patients had clinical myopathy, and underwent
      neuromuscular evaluation with information recorded on timing and dosage of ZDV.
      All underwent muscle biopsies and samples were examined without knowledge of
      clinical history or ZDV status. Biopsy samples were evaluated by light and
      electron microscopy. Mitochondrial abnormalities were seen in ZDV-treated and 
      naive groups, and did not correlate with ZDV exposure or cumulative ZDV dosage.
      Mitochondrial abnormalities displayed significant correlation with the presence
      and severity of myofiber degeneration on biopsy, regardless of ZDV status. As
      mitochondrial abnormalities reflect myofiber degeneration, present in both
      patient groups, they may not be used as evidence of primary mitochondrial
      dysfunction. The etiology of myofiber degeneration in patients with HIV
      infection, whether ZDV-exposed or -naive, remains unclear.

PMID- 8546028
TI  - Temporal evolution of neuropathologic changes in an immature rat model of
      cerebral hypoxia: a light microscopic study.
AB  - The sequential evolution of neuropathologic changes was studied in an immature
      model of cerebral hypoxia-ischemia. According, 7-day postnatal rats were
      subjected to unilateral common carotid artery ligation combined with 2 h of
      hypoxia (breathing in 8% oxygen) and their brains were examined by light
      microscopy at recovery intervals ranging from 0 to 3 weeks. Immediately following
      hypoxia, a large area with a pale staining border was noted occupying most of the
      cerebral hemisphere ipsilateral (IL) to the occluded common carotid artery; in
      approximately half of the brains the dorsomedial cortex of the contralateral (CL)
      hemisphere was also involved. Most neurons in the pale area had nuclei containing
      a coarse granular condensation of chromatin. Within a few hours, the majority of
      neurons in the IL hemisphere had developed pyknotic nuclei and clear or
      eosinophilic perikarya. After 24 h these changes had evolved in the majority of
      brains into coagulation necrosis (infarction) in the IL hemisphere and foci of
      selective neuronal necrosis in the CL cortex. Within a few days infarcts became
      partially cavitated, and by 3 weeks a smooth-walled cystic infarct had developed.
      Activated microglia/macrophages and reactive astrocytes were first seen at 4 and
      24 h, respectively. No parenchymal neutrophilic infiltrate was seen at any time
      point.

PMID- 8546030
TI  - Cystic leukomalacia in the cerebellar folia of premature infants.
AB  - Cystic necrosis in the cerebellar white matter was found in three premature
      infants. The necrosis was characteristically localized in the center of the white
      matter of the superficial cerebellar folia, sparing the overlying cortex. The
      patients were aged between 28 and 34 gestational weeks, and had a clinical
      history of severe systemic hypotension. Thus, cystic leukomalacia represents a
      characteristic brain lesion in premature infants which may be caused by
      cerebellar hypoperfusion.

PMID- 8546029
TI  - Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis:
      an immunohistochemical, ultrastructural, and immunoelectron and microscopic
      study.
AB  - The cellular nature of the giant eosinophilic cells of tuber and of the cells
      comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS)
      remains unclear. To assess the characteristics of these lesions, 13 tubers and 6
      SEGA were immunohistochemically studied with glial and neuron-associated
      antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were
      subjected to immunoelectron microscopic study for glial fibrillary acidic protein
      (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for
      vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found
      to a various extent to be reactive for neuron-associated antigens, including
      neurofilament (NF) proteins (38%) or class III beta-tubulin (77%). SEGA also
      showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF
      epitopes, class III beta-tubulin, and calbindin 28-kD were expressed in 2 (33%),
      5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin
      (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and
      neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the
      giant cells of tubers and the cells of SEGA contained numerous intermediate
      filaments, frequent lysosomes and occasional rectangular or rhomboid membrane
      bound crystalloids exhibiting lamellar periodicity and structural transition to
      lysosomes. Some SEGA cells showed features suggestive of neuronal
      differentiation, including stacks of rough endoplasmic reticulum, occasional
      microtubules and a few dense-core granules. Furthermore, in one case of tuber, a
      process of a single large cell was seen to be engaged in synapse formation.
      Intermediate filaments within a few cells of both lesions were decorated by gold
      particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non
      membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive
      particles, whereas the latter could not be detected in tuber. The present study
      provides further evidence of divergent glioneuronal differentiation, both in the
      giant cells of tubers and the cells of SEGA. The findings of similar cells at
      different sites, including the subependymal zone, white matter ("heterotopias"),
      and cortex indirectly supports the idea that these lesions of TS result from a
      migration abnormality.

PMID- 8546031
TI  - Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy:
      correlation with type of diabetes.
AB  - Observations were made on myelinated fibre regeneration in diabetic sensory
      polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that
      regenerative clusters initially develop within abnormally persistent Schwann cell
      basal laminal tubes. The number of regenerating fibres, identified by light
      microscopy, was found to decline in proportion to the reduction in total
      myelinated fibre density. The relative number of regenerating fibres was
      significantly greater in patients with insulin-dependent as compared with those
      with non-insulin-dependent diabetes after correction for age. There was a slight
      negative correlation between the relative proportion of regenerating fibres and
      age, but this was not statistically significant. The progressive reduction in the
      number of regenerating fibres with declining total fibre density indicates that
      axonal regeneration fails with advancing neuropathy. The production of nerve
      growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be
      important for axonal regeneration. To investigate whether the failure of axonal
      regeneration could be related to a lack of NGF receptor production by Schwann
      cells, we examined the expression of p75 NGF receptors by Bungner bands
      immunocytochemically. In comparison with other types of peripheral neuropathy,
      p75 NGF receptor expression appeared to take place normally. It is concluded that
      failure of axonal regeneration constitutes an important component in diabetic
      neuropathy. Its explanation requires further investigation.

PMID- 8546032
TI  - Interacting effects of Ca2+ and hypoxia in the induction of sarcolemmal damage in
      mouse diaphragm in vitro.
AB  - Experiments have been undertaken to investigate the basis for the selective
      damage of centrally placed fibres in mouse diaphragms exposed to Ca2+ loading in
      vitro. Incubation under hypoxic conditions (non-aerated saline) for 30 min had no
      discernible effect on the muscle. Incubation for 120 min led to permeabilisation
      of the sarcolemma (assayed by penetration of Procion Yellow) in 54% of cells.
      Sarcolemmal permeabilisation was almost completely restricted to centrally placed
      cells, as has previously been described for the effects of the Ca2+ channel
      agonist Bay K 8644. Ultrastructural damage to the myofibrils and mitochondrial
      swelling were also widespread amongst centrally placed cells. Permeabilisation
      was inhibited when hypoxic incubations were carried out in Ca(2+)-free saline.
      Incubation in hypoxic Ca(2+)-containing saline for 30 min followed by further
      incubation in Ca(2+)-free, hypoxic saline, up to a total of 120 min, resulted in
      permeabilisation similar to that seen in muscles incubated for 120 min in Ca(2+)
      containing, hypoxic saline. It is suggested that selective damage to central
      fibres induced by Ca2+ loading resulting from treatment with Bay K 8644 is
      related to increased oxygen demand.

PMID- 8546033
TI  - Senile plaques in an aged two-humped (Bactrian) camel (Camelus bactrianus).
AB  - Senile plaques with beta-protein as a major constituent are a conspicuous feature
      in the brains of aged humans, monkeys, dogs, and bears. We found cerebral senile
      plaques of the diffuse and primitive type, but not the classical type, in an aged
      female camel of more than 20 years old. The senile plaques and a few cortical
      capillaries were immunoreactive with anti-beta-protein serum. Congophilic amyloid
      deposition was detected in a small number of the capillaries, but not in the
      senile plaques. We believe this to be the first detailed report of senile plaques
      in a herbivore, and these findings suggest the possibility of senile plaque
      formation in a wide variety of mammalian species.

PMID- 8546034
TI  - Is Phlebotomus (Larroussius) orientalis a vector of visceral leishmaniasis in
      south-west Ethiopia?

PMID- 8546035
TI  - Differences in eosinophil and neutrophil chemotactic responses in sowda and
      generalized form of onchocerciasis.
AB  - Extravasation of host's leukocytes from blood vessels into inflammatory tissues
      represents a prerequisite for a subsequent interaction with invaded parasites.
      The migratory responses of eosinophilic and neutrophilic granulocytes in the
      polar forms of the filarial infection onchocerciasis were investigated. The
      hyporeactive, generalized form, the chronic hyperreactive (sowda) form and
      persons without signs of onchocerciasis from a hypoendemic area for
      onchocerciasis were compared. Eosinophils from sowda patients responded more
      strongly to the inflammatory mediator platelet-activating factor (PAF) than those
      from generalized patients and persons without onchocerciasis. The most
      significant differences were found between the sowda group and a subgroup of the
      generalized form with 16-80 microfilariae/mg skin (P<0.05) while patients with
      low microfilarial density exhibited chemotactic responses similar to the sowda
      group. In contrast to the strong eosinophil response, neutrophils from sowda
      patients appeared unreactive to PAF and the tripeptide activator formyl-methionyl
      leucyl-phenylalanine (fMLP), thereby differing from both other groups. Laboratory
      data confirmed a state of hyperreactivity in sowda patients similarly found in
      generalized patients with low microfilarial density and contrasting with those
      with a microfilarial density of 16-80 mf/mg. The results revealed an inverse
      chemotactic responsiveness of eosinophil and neutrophil granulocytes in sowda
      patients and strengthened the observation of a spectrum of host's responsiveness
      in onchocerciasis.

PMID- 8546036
TI  - A field trial with Lambda-cyhalothrin (ICON) for the intradomiciliary control of
      malaria transmitted by Anopheles darlingi root in Rondonia, Brazil.
AB  - A two stage field trial comparing the effects of Lambdacyhalothrin (ICON) and DDT
      when used as residual sprays on the inside surfaces of houses, was conducted in
      the Machadinho and Jaru areas of Rodonia, Brazil, in 1987 and 1988. In 1987
      houses along two 16 km contiguous stretches of a main and a side road were
      sprayed and the effects on malaria vectors monitored for the succeeding year. In
      the second stage approximately 55,000 houses in both districts were sprayed with
      ICON and the effect on malaria incidence measured by passive case detection. Of
      the eleven species of Anopheles caught in indoor and peridomiciliary collections
      A. darlingi was the commonest and is recognised as the most important vector in
      Brazil. ICON at either of two concentrations in bioassays killed more mosquitoes
      than DDT at each test from seven to twelve months after spraying. A rise in the
      number of A. darlingi collected eight months after spraying with DDT was not so
      marked in the ICON areas. Side effects of the insecticide were limited. The
      number of reported Plasmodium falciparum cases in the second phase declined 76%
      in Machadinho after spraying with ICON to 2851 cases. In Jaru there was a 28%
      reduction. The observed efficacy of the insecticide, its ready acceptance by the
      local populace, and its cost effectiveness make it a more useful insecticide for
      anti-malaria campaigns than DDT.

PMID- 8546037
TI  - Biological and genetic analysis of a longitudinal collection of Giardia samples
      derived from humans.
AB  - Duodenal aspirates from children investigated for diarrhoea have been examined
      for the presence of Giardia over an eleven year period, and where possible, in
      vitro or in vivo Giardia cultures in mice were established. Based on biochemical
      characteristics of electrophoretic karyotype, RFLP analysis and rDNA
      hybridization studies of 40 stocks at least two major varieties, or demes, of
      Giardia have infected the population of South East Queensland and environs during
      this period. These demes carried different rDNA repeat units and differed
      markedly in both the electrophoretic karyotype pattern and the molar
      representation of chromosome bands. From 1983 to 1991 only one deme was
      documented. The first evidence of a new deme seen in local children occurred in
      1991 and was followed by a predominance of this deme in 1993. These 40 stocks do
      not represent all positive samples. Other stocks established in vivo were not
      able to be cultured in vitro, and these probably represent other demes. Since all
      of the stocks established in vivo were not able to be cultured in vitro, and
      these probably represent other demes. Since all of the stocks were derived from
      children with similar chronic symptoms it appears that at least two demes of
      Giardia are pathogenic.

PMID- 8546038
TI  - The potential for malaria control with the biological larvicide Bacillus
      thuringiensis israelensis (Bti) in Peru and Ecuador.
AB  - A study on the efficacy of Bti spraying in mosquito breeding places was
      undertaken in the Pacific coast of Peru and Ecuador and in the Amazon area of
      Peru. It was shown that Bti is a powerful larvicide for Anopheles larvae,
      although it sinks quickly, whereas Anopheles larvae feed at the water surface.
      The duration of its effect was less than 7 days with the exception of the Amazon
      area of Peru, where it was approximately 10 days. In two study areas, Bti was
      sprayed weekly over periods of 10 and 7 weeks, respectively, and the adult
      mosquito densities were monitored. The Anopheles adult density (bites per person
      per hour on human baits) was reduced by an average of 70% in one area and by up
      to 50% in the other. This means that Bti spraying can potentially be an important
      component of a modified malaria control strategy.

PMID- 8546040
TI  - Removal of facial brown spots.

PMID- 8546039
TI  - Carbohydrate epitopes of Entamoeba histolytica cell surface glycoproteins are
      major targets of the human humoral response.
AB  - The antigens of Entamoeba histolytica recognized by antibodies in 11 individual
      sera from patients treated for amebic liver abscess were determined both by
      immunoprecipitation of metabolically-radiolabeled whole trophozoite proteins and
      by immunoblotting.Collectively, twenty-s even antigens ranging from 167 to 21 kDa
      were detected in immunoblots of whole trophozoite extracts; eight of these were
      recognized by all tested patient sera. Immunoprecipitation studies also revealed
      a complex amebic antigenic profile. Of a total of twenty immunoprecipitated
      polypeptides (from 200 to 24 kDa), seventeen were uniquely recognized by the
      patient sera. Eight of these seventeen antigens were immunoprecipitated by most
      immune sera. The cellular localization of trophozoite antigens was determined by
      analyzing plasma membrane and soluble cytosol fractions. Plasma membranes
      contained virtually as many antigenic moieties as the total trophozoite extract;
      in contrast, the soluble fraction was antigenically less complex. Mild periodate
      oxidation of plasma membrane antigens indicated that surface glycoproteins are
      highly immunogenic for the human host and that antibodies to their carbohydrate
      epitopes are a major component of the total response of most patients.

PMID- 8546041
TI  - Human papillomavirus infection: treatment options for warts.
AB  - Human papillomavirus can produce verrucae, or warts, on cutaneous and mucosal
      surfaces. Although the diagnosis is usually straightforward, issues regarding the
      need for treatment and the choice of treatment are complex. The rationale for the
      treatment of viral warts is based on the prevention of spread to other areas of
      the body or to other people; the prevention of irritation, bleeding and other
      unwanted local effects of the wart; cosmetic and psychosocial considerations, and
      the possible association with neoplasia. A significant proportion of warts
      resolve spontaneously within two years. Many treatment options appropriate to
      primary care are available, including local application of salicylic acid,
      cantharidin, liquid nitrogen and podophyllum. Direct injection of interferon is a
      choice in selected cases. The decision to treat and the choice of modality must
      be individualized.

PMID- 8546042
TI  - Macrocytic anemia.
AB  - In approximately 2 to 4 percent of patients, laboratory evidence of macrocytosis
      is found. Macrocytic anemias are classified as those resulting from disorders of
      DNA synthesis of erythrocyte precursors in bone marrow (megaloblastic anemias) or
      those caused primarily by alcoholism, liver disease and hypothyroidism
      (nonmegaloblastic anemias). A blood smear should be performed to differentiate
      the two forms. Neutrophil hypersegmentation is one of the most sensitive and
      specific signs of megaloblastic anemia. Other testing should include vitamin B12
      and red blood cell folate levels, reticulocyte count, and thyroid and liver
      function tests. The Schilling test can determine if B12 can be absorbed and, if
      not, whether adding intrinsic factor corrects the malabsorption. The most common
      form of nonmegaloblastic macrocytic anemia results from alcoholism.
      Nonmegaloblastic macrocytic anemias may be accompanied by increased reticulocyte
      counts (hemolysis, hemorrhage) or by normal or decreased reticulocyte counts
      (alcoholism, liver disease, hypothyroidism and various bone marrow disorders).

PMID- 8546043
TI  - Treatment of menorrhagia due to dysfunctional uterine bleeding.
AB  - Menorrhagia due to dysfunctional uterine bleeding can be treated medically or
      surgically. Medical therapy is associated with less morbidity and less profound
      effects on body image and fertility. Nonsteroidal anti-inflammatory drugs are the
      agents of choice for menorrhagia, although oral contraceptives, danazol and newer
      hormonal agents may also be used. Hysterectomy has been the surgical procedure
      traditionally used to treat menorrhagia, but excisional or "rollerball"
      endometrial resection may improve or cure this problem with a shorter hospital
      stay, a lower cost and less morbidity.

PMID- 8546044
TI  - Urinary tract infections in elderly women.
AB  - Although bacteriuria is common in older women, it is important to differentiate
      between symptomatic and asymptomatic urinary tract infections. Recent evidence
      suggests that treatment of asymptomatic bacteriuria may not be necessary.
      Symptomatic bacteriuria may occur with low colony counts cultured from either
      clean-catch or catheter-obtained specimens. Although few studies have targeted
      elderly women, longer treatment with a broad-spectrum antibiotic is recommended
      for this group. To minimize recurrence, attention should be paid to predisposing
      factors, particularly impaired bladder emptying, genital prolapse, urolithiasis,
      estrogen depletion and perineal hygiene.

PMID- 8546045
TI  - Management of acetaminophen toxicity.
AB  - Acetaminophen poisoning is a significant medical problem in the United States and
      is frequently managed by family physicians. The primary clinical effect of
      acetaminophen poisoning is hepatotoxicity that occurs after ingestion of large
      single doses of acetaminophen or after ingestion of smaller doses in patients
      with hepatic metabolism that is altered by drugs or concurrent medical
      conditions. Hepatocellular damage is probably caused by accumulation of the toxic
      intermediate metabolite N-acetyl-p-benzoquinoneimine when hepatic glutathione
      stores are depleted. Treatment of acetaminophen poisoning consists of preventing
      gastrointestinal absorption of the drug, use of the antidote N-acetylcysteine and
      supportive care.

PMID- 8546046
TI  - Recognizing primary biliary cirrhosis and primary sclerosing cholangitis.
AB  - Nonsuppurative cholangiopathies such as primary biliary cirrhosis and primary
      sclerosing cholangitis are chronic cholestatic liver diseases that result from
      inflammation of the biliary system. Recent advances in management options for
      patients with primary biliary cirrhosis and primary sclerosing cholangitis have
      facilitated treatment by family physicians. Patients with significant laboratory
      abnormalities on liver tests for cholestasis should be evaluated for possible
      primary biliary cirrhosis or primary sclerosing cholangitis. Investigation with
      liver biopsy and endoscopic retrograde cholangiopancreatography should be
      considered if abnormal biochemical findings remain unexplained after a careful
      history and physical examination are performed, a thorough medication history is
      obtained and abdominal ultrasonography is conducted to search for biliary
      obstruction.

PMID- 8546047
TI  - Improving patient education for patients with low literacy skills.
AB  - Patients who misunderstand their diagnosis and treatment plans usually exhibit
      poor compliance. The 90 million adult Americans with low literacy skills struggle
      to understand such essential health information as discharge instructions,
      consent forms, oral instructions and drug labels. The Joint Commission on
      Accreditation of Health Organizations (JCAHO) now requires that instructions be
      given on a level understandable to the patient. Most physicians tend to give too
      much information on too high a level for many patients to understand. Physicians
      who speak in simpler language, repeat their instructions and demonstrate key
      points, while avoiding too many directives, enhance their patients'
      understanding. Combining easy-to-read written patient education materials with
      oral instructions has been shown to greatly enhance patient understanding. To be
      effective with patients whose literacy skills are low, patient education
      materials should be short and simple, contain culturally sensitive graphics and
      encourage desired behavior. Compliance with therapy also may be improved by
      including family members in the patient education process.

PMID- 8546048
TI  - Thyroid disease during pregnancy.
AB  - Physiologic changes in metabolism may make thyroid diseases difficult to diagnose
      during pregnancy. Such diagnoses depend principally on clinical acumen and an
      understanding of the alterations of laboratory values, particularly thyroid
      stimulating hormone (TSH), induced by pregnancy. Untreated thyrotoxicosis may
      lead to abortion, stillbirth, neonatal death and low birth weight. The principal
      cause of thyrotoxicosis in pregnancy is Graves' disease, which may be treated
      with antithyroid drugs or surgery. The use of radioactive iodine is absolutely
      contraindicated during pregnancy. Hypothyroidism during pregnancy is associated
      with hypertension and premature labor. The goal of thyroxine replacement therapy
      is to maintain serum TSH levels in the normal range. Many thyroid conditions and
      treatments directly affect the fetus and the principal antithyroid drugs are
      secreted in breast milk. Both the mother and neonate require monitoring. In
      addition, autoimmune postpartum thyroiditis may recur following each pregnancy in
      susceptible patients.

PMID- 8546049
TI  - Renal and electrolyte complications associated with antibiotic therapy.
AB  - Adverse effects of antibiotics generally are minimal, but it is necessary to
      remain vigilant for potentially serious sequelae, such as unusual forms of renal
      failure, acidosis and electrolyte abnormalities. Avoiding potentially nephrotoxic
      drug combinations and monitoring drug levels of nephrotoxic agents such as
      vancomycin and aminoglycosides should be routine. However, with prolonged use of
      certain antibiotics, levels of electrolytes, creatinine and blood urea nitrogen
      should be periodically checked. Elderly and debilitated patients or patients with
      preexisting renal insufficiency are at particularly high risk for unexpected
      complications from antimicrobial therapy. All antibiotics have the potential to
      cause acute interstitial nephritis, which may be manifested by acute renal
      failure.

PMID- 8546050
TI  - New applications of laparoscopy in gastrointestinal surgery.
AB  - Although laparoscopy has been available since the turn of the century, the
      technique did not become widely accepted for gastrointestinal surgery until it
      was used in cholecystectomy. Since then, various gastrointestinal operations have
      been performed using laparoscopic guidance. Laparoscopic operations must conform
      to principles for open general surgery, especially in cases of oncologic
      resection. Procedures for treatment of conditions such as hiatal hernia,
      gastroesophageal reflux, intractable peptic ulcer disease, bypass for malignant
      pancreatic obstruction and repair of rectal prolapse have received immediate
      acceptance. Other procedures, such as Whipple's operation and colectomy for
      cancer, have met with a more guarded response.

PMID- 8546051
TI  - Sleep apnea: is your patient at risk? National Heart, Lung, and Blood Institute
      Working Group on Sleep Apnea.
AB  - Obstructive sleep apnea is a breathing disorder characterized by repeated
      collapse of the upper airway during sleep, with cessation of breathing. Four
      percent of middle-aged men and 2 percent of middle-aged women meet minimal
      criteria for the sleep apnea syndrome. Risk factors include loud, chronic
      snoring, obesity (especially nuchal), hypertension, excessive daytime sleepiness,
      and an increased tendency for automobile and work-related accidents.
      Cardiovascular comorbidity and complications include systemic hypertension,
      arrhythmias and possibly myocardial ischemia and myocardial infarction in
      patients with coronary artery disease. Diagnosis is confirmed by a sleep study;
      currently, polysomnography is the optimum test. Treatment options range from
      behavioral therapy alone for mild cases to a combination of behavioral approaches
      and continuous positive airway pressure and/or surgery for moderate and severe
      cases. Continuous positive airway pressure is the most effective noninvasive
      treatment. Primary care physicians play a key role in the identification,
      management and follow-up of patients with sleep apnea.

PMID- 8546052
TI  - Childhood behavior problems.
AB  - Educating parents about normal, age-appropriate behavior in their children,
      teaching them basic behavioral techniques (such as the time-out and positive
      reward systems) and giving them specific suggestions for intervention can
      increase parental confidence and decrease anxiety. Anticipating problems before
      they develop can help parents prevent inappropriate behavior patterns from
      developing in their children and may decrease abusive behavior.

PMID- 8546053
TI  - Electroconvulsive therapy: a guide for family physicians.
AB  - Electroconvulsive therapy, which works by creating a generalized seizure, is used
      most frequently to treat medication-resistant depression. Other indications for
      electroconvulsive therapy includes severe depression with suicidal ideation,
      acute mania and severe psychiatric illness with food and fluid refusal.
      Electroconvulsive therapy may be administered as an inpatient or outpatient
      procedure. Treatments are usually administered three times a week for six to 12
      treatments. Before this therapy is used, a thorough medical and anesthetic
      history should be obtained, and a complete physical examination, an
      electrocardiogram and appropriate laboratory studies should be performed to rule
      out anemia, electrolyte imbalances, and cardiopulmonary and neurologic risk
      factors. Heart rate and rhythm, oxygenation, blood pressure and, often, the
      electroencephalogram are monitored continuously while the patient is anesthetized
      with a short-acting hypnotic agent and a muscle depolarizing agent. After
      electroconvulsive therapy, antidepressant or lithium therapy significantly
      reduces the symptom relapse rate.

PMID- 8546054
TI  - Proton pump inhibitors: new drugs and indications.
AB  - Proton pump inhibitors irreversibly inhibit the enzyme hydrogen-potassium
      adenosine triphosphatase (H(+)-K(+)-ATPase), which suppresses acid production in
      the parietal cell of the stomach. Omeprazole, the prototype proton pump
      inhibitor, has proved to be very effective. However, newer agents are being
      designed to provide even more potent acid suppression and longer-acting proton
      pump inhibition, with the goal of further controlling gastric hypersecretion.
      Lansoprazole is the second proton pump inhibitor available on the market.
      Pantoprazole is not yet available for general use in the United States. However,
      each of these drugs is slightly different from omeprazole, thus offering some
      possible clinical advantages. Compared with omeprazole, lansoprazole has a longer
      duration of action and improved activity against Helicobacter pylori, while
      pantoprazole has less interaction with the cytochrome P-450 system and more
      predictable bioavailability. All three agents have similarly high healing rates
      for acid peptic diseases and appear to be superior to histamine2-receptor
      antagonists.

PMID- 8546055
TI  - Allergy and immunology. American Academy of Family Physicians.

PMID- 8546056
TI  - Recommendations issued for preventing the spread of vancomycin resistance.

PMID- 8546057
TI  - AAFP, AAP and ACIP release new childhood immunization schedule.

PMID- 8546058
TI  - Sleep apnea: are you missing the diagnosis?

PMID- 8546059
TI  - January-June 1996 childhood immunization schedule.

PMID- 8546060
TI  - Planning the family physician workforce.

PMID- 8546061
TI  - Family physician workforce reform: AAFP recommendations. Board of Directors,
      American Academy of Family Physicians.

PMID- 8546062
TI  - Chiropractic manipulation and atherosclerotic emboli to the eye.

PMID- 8546063
TI  - Fibromyalgia: misdiagnosed, mistreated and misunderstood?

PMID- 8546064
TI  - Techniques for performing neonatal circumcision.

PMID- 8546066
TI  - Techniques for performing neonatal circumcision.

PMID- 8546065
TI  - Techniques for performing neonatal circumcision.

PMID- 8546067
TI  - Techniques for performing neonatal circumcision.

PMID- 8546068
TI  - Sterile cockpit.

PMID- 8546069
TI  - Myths about patient compliance.

PMID- 8546070
TI  - Avoiding liability problems. American Pharmaceutical Association.

PMID- 8546071
TI  - Dispensing errors and counseling in community practice.
AB  - A disguised-patient technique was used to study the nature and frequency of
      dispensing errors and quality of patient medication counseling in 100 randomly
      selected community pharmacies. Analysis of 100 prescription orders dispensed
      detected 24 dispensing errors, of which 4 were clinically significant. Oral
      counseling was provided to 64 of the patients, covering an average of 3 of the 14
      categories of drug information that the Omnibus Budget Reconciliation Act of 1990
      (OBRA '90) requires pharmacists to consider when counseling Medicaid patients. In
      addition to prescriber's label instructions, pharmacists provided written
      counseling information, including auxiliary labels and receipts, to 98% of the
      patients, but it covered only an average of six OBRA '90 categories. The results
      suggest that problems with the quality of community pharmacy medication
      counseling and dispensing accuracy require immediate attention.

PMID- 8546072
TI  - Liability and the changing role of pharmacists.

PMID- 8546073
TI  - Treatment of community-acquired urinary tract infections.

PMID- 8546074
TI  - GAO report on need for a third class: 'prove it'.

PMID- 8546075
TI  - Genetically engineered vaccines.

PMID- 8546076
TI  - Impact of plaque morphology and composition on the mechanisms of lumen
      enlargement using intracoronary ultrasound and quantitative angiography after
      balloon angioplasty.
AB  - Limited information is provided by angiography on plaque morphology and
      composition before balloon angioplasty. Identification of plaques associated with
      reduced lumen gain or a high complication rate may provide the rationale for
      using alternative revascularization devices. We studied 60 patients with
      quantitative angiography and intracoronary ultrasound (ICUS) before and after
      balloon dilation. Angiography was used to measure transient wall stretch and
      elastic recoil. ICUS was used to investigate the mechanisms of lumen enlargement
      among different plaque compositions and in the presence of a disease-free wall
      (minimal thickness < or = 0.6 mm). Compared with ultrasound, angiography
      underestimated the presence of vessel calcification (13% vs 78%), lumen
      eccentricity (35% vs 62%), and wall dissection (32% vs 57%). ICUS measurements
      showed that balloon angioplasty increased lumen area from 1.82 +/- 0.51 to 4.81
      +/- 1.43 mm2. Lumen enlargement was the result of the combined effect of an
      increase in the total cross-sectional area of the vessel (wall stretching, 43%)
      and of a reduction in the area occupied by the plaque (plaque compression or
      redistribution, 57%). Vessels with a disease-free wall had smaller lumen gain
      than other types of vessels (2.13 +/- 1.26 vs 3.59 +/- mm2, respectively, p <
      0.01). Wall stretching was the most important mechanism of lumen enlargement in
      vessels with a disease-free wall (79% vs 37% in the other vessels). Angiography
      revealed a direct correlation between temporary stretch and elastic recoil that
      was responsible for 26% of the loss of the potential lumen gain. Thus, lumen
      enlargement after balloon angioplasty is the combined result of wall stretch and
      plaque compression or redistribution. ICUS indicates that vessels with a remnant
      arc of disease-free wall are dilated mainly by wall stretching compared with
      other types of vessels and are associated with a smaller lumen gain.

PMID- 8546077
TI  - Evidence for free radical generation after primary percutaneous transluminal
      coronary angioplasty recanalization in acute myocardial infarction.
AB  - In animal models, oxygen-derived free radicals have been found to be important
      mediators of reperfusion injury to ischemic but viable myocardium. However, in
      humans, there is no direct evidence of free radical production after the
      restoration of coronary artery patency in acute myocardial infarction. The
      purpose of this study was to quantitate and assess the time course of free
      radical production in coronary venous outflow in patients with acute myocardial
      infarction undergoing successful recanalization of the infarct-related artery by
      primary percutaneous transluminal coronary angioplasty (PTCA). Primary PTCA was
      performed in 17 patients with acute myocardial infarction of < 6 hours duration.
      Direct free radical production was assessed by coronary venous effluent blood
      sampling before PTCA and at timed intervals up to 24 hours (or 48 hours in 6
      patients) after recanalization. All samples were added to the spin trapping agent
      alpha-phenyl N-tert butyl nitrone and analyzed by electron paramagnetic resonance
      spectroscopy. Vessel patency resulted in a sharp increase in free radical signal.
      Relative to the level before PTCA, the changes reached statistical significance
      after only 15 minutes (p < 0.05). Peak signals were observed between 1 1/2 and 3
      1/2 hours (p < 0.001), then declined up to 5 hours. A second increase in signal
      level was detected between 18 and 24 hours despite no angiographic evidence of
      reocclusion. A gradual decline was observed after 24 hours. These findings
      provide the first direct and quantitative evidence of free radical production in
      the immediate postrecanalization phase after thrombotic occlusion of a major
      coronary artery in humans.

PMID- 8546078
TI  - Correlation between clinical and morphologic findings in unstable angina.
AB  - This study was undertaken to verify the hypothesis that the discrepant findings
      in published reports on the prevalence of thrombus in unstable angina depend on
      the inclusion of different clinical subsets in the various studies. We therefore
      correlated the clinical characteristics of patients included under the label of
      unstable angina with the morphologic features assessed by coronary angiography
      and intravascular ultrasound, and with histopathologic findings of atherectomy
      specimens. Fifty-eight patients with unstable angina (class B of the Braunwald
      classification) undergoing coronary arteriography followed by either coronary
      angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied.
      Fifteen patients were in class IB and 43 were in class II to IIIB. Among these 43
      patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had
      ST-segment depression, and 26 developed negative T waves on the baseline
      electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting
      chest pain. Intravascular ultrasound examination of the culprit lesion was
      performed in 43 patients before the interventional procedure, and histopathologic
      analysis of atherectomy specimens was performed in 38 patients. Complex lesion
      morphology by angiography was observed in 31 patients (53%) without any
      significant relation to various clinical subsets. Patients in Braunwald class IB
      had more calcific plaques than patients in class II to IIIB (p < 0.001). Among
      patients with angina at rest, those with negative T waves on the baseline ECG, as
      well as those with transient ST elevation during pain, had a significantly higher
      incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy
      specimens revealed acute coronary lesions (thrombus and/or intraplaque
      hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was
      significantly higher in patients with than without negative T waves on the
      baseline ECG (p = 0.005), and increased further when negative T waves were
      combined with ST elevation during pain (p = 0.001). Multivariate analysis
      revealed that the presence orf negative T waves on the baseline ECG was the only
      explanatory variable related to the presence of acute coronary lesions by
      histology (p = 0.03). Patient subsets included in the broad spectrum of unstable
      angina have different morphologic features and incidence of acute coronary
      lesions by histology. These data provide an explanation for the discrepant
      findings in published reports on the relevance of thrombus formation in the
      pathogenesis of unstable angina.

PMID- 8546079
TI  - Use of ventricular premature complexes for risk stratification after acute
      myocardial infarction in the thrombolytic era.
AB  - The independent predictive role of ventricular premature complex (VPC) frequency
      in the stratification of mortality risk after acute myocardial infarction (AMI)
      was established in the prethrombolytic era by extensive multicenter trials.
      Thrombolysis has lead to important changes in the natural history of patients
      after AMI, so that reassessment of established risk factors is now required. The
      prognostic significance of VPCs was assessed in 680 patients, of whom 379
      received early thrombolytic therapy. All patients underwent 24-hour Holter
      monitoring in a drug-free state between 6 and 10 days after AMI. Patients were
      followed up for 1 to 8 years. During the first year of follow-up, cardiac death
      occurred in 33 patients, sudden death in 24, and sustained ventricular
      tachycardia in 20. Mean VPC frequency was significantly higher in patients who
      died of cardiac causes, in those who died suddenly, and in those with arrhythmic
      events during the first year of follow-up. This was also true when patients who
      did and did not undergo thrombolysis were considered separately. The positive
      predictive accuracy of VPC frequency in predicting adverse cardiac events was
      greater in patients who did than did not undergo thrombolysis. At a sensitivity
      level of 40%, the positive predictive accuracy for cardiac mortality and
      arrhythmic events for the group with thrombolysis was 19.4% and 25.8%,
      respectively, compared with 16% and 16% for those without thrombolysis. Moreover,
      the highest VPC frequency for the dichotomy of patients into high-and low-risk
      groups was 25 VPCs/hour for patients without thrombolysis. VPC frequency appears
      to be more highly predictive of prognosis after AMI in patients who have
      undergone thrombolysis than in those who have not, but the optimal frequency for
      dichotomy is higher in the former.

PMID- 8546080
TI  - Cost and appropriateness of radionuclide exercise stress testing by cardiologists
      and non-cardiologists.
AB  - The hypothesis that a diagnostic evaluation performed by a generalist is less
      expensive than that performed by a specialist is untested. We retrospectively
      evaluated the indications and financial ramifications of radionuclide exercise
      stress testing by cardiologists and noncardiologists in 1,902 consecutive adults
      with normal resting electrocardiograms. Subjects completed radionuclide exercise
      tests for the diagnosis or management of coronary artery disease during a 14
      month period. Tests were considered "indicated" or "not indicated" based on
      criteria determined from published reports and established practice guidelines.
      Savings in costs and charges were determined for a strategy of referral to a
      cardiologist before ordering tests. Non-cardiologists ordered more tests that
      were not indicated than cardiologists (69.6% vs 36.2%, chi-square = 209.07, p <
      0.00001). Non-cardiologists also ordered tests that were not indicated in
      patients with (chi-square = 110.02, p < 0.00001) and without (chi-square =
      110.02, p < 0.00001) and without (chi-square = 45.44, p < 0.00001) chest pain.
      Tests that were not indicated resulted in excess costs of $591,384 and excess
      charges of $1,082,400. Referral to a cardiologist before ordering tests could
      have saved $63,257 in costs and $169,800 in charges. Both cardiologists and non
      cardiologists overutilized radionuclide exercise stress test; however, non
      cardiologists were more likely to order tests that were not indicated. A strategy
      of referral to a cardiologist before ordering tests may be cost-effective in this
      population.

PMID- 8546081
TI  - Additive value of thallium single-photon emission computed tomography myocardial
      imaging for prediction of perioperative events in clinically selected high
      cardiac risk patients having abdominal aortic surgery.
AB  - The present study was designed to prospectively evaluate whether reinjection
      thallium-201 single-photon emission computed tomography (SPECT) has a significant
      additive predictive value for occurrence of perioperative cardiac events in
      clinically selected patients at high cardiac risk undergoing abdominal aortic
      surgery. Of a group of 517 consecutive patients referred, 134 had > or = 2 of the
      following clinical or electrocardiographic cardiac risk variables: age > 70
      years; history of myocardial infarction, angina, or congestive heart failure;
      diabetes mellitus; hypertension with severe left ventricular hypertrophy; and Q
      waves or ischemic ST-segment abnormalities on electrocardiogram at rest.
      Operation was performed after thallium SPECT study. Twelve patients (9%) had
      major perioperative events (cardiac death or nonfatal myocardial infarction) and
      18 patients had other cardiac events (unstable angina, congestive heart failure,
      or severe ventricular tachyarrhythmia). Variables correlated with the occurrence
      of major events were history of myocardial infarction (p < 0.05) and the presence
      (p < 0.001) and number of segments with thallium reversible defects (p < 0.001).
      In multivariate analysis, history of myocardial infarction (p < 0.05) and the
      number of segments with reversible thallium defects (p < 0.001) were independent
      predictors. When all the cardiac events were taken into consideration, all the
      previous variables, as well as Q waves and ischemic ST abnormalities on the
      electrocardiogram, showed significant predictive value in both univariate and
      multivariate analyses. Furthermore, thallium SPECT imaging has an additive
      predictive value for major cardiac events over clinical and electrocardiographic
      risk factors. When performed on clinically selected patients at high cardiac risk
      undergoing abdominal aortic surgery, thallium SPECT demonstrates significant
      prognostic value for cardiac events over that provided by clinical variables
      alone.

PMID- 8546082
TI  - Variable response of the peripheral circulation to acetylcholine in patients with
      coronary artery disease.
AB  - The purpose of this study was to assess endothelium-mediated vasodilation in the
      peripheral circulation of patients with coronary artery disease who are free from
      hypertension, hypercholesterolemia, diabetes mellitus, and congestive heart
      failure. The vascular response of the superficial femoral artery to an
      endothelium-dependent (i.e., acetylcholine 10-7, 10-6, and 10-5 mol/L) and to an
      endothelium-independent (i.e., nitroglycerin 10-8 and 10-6 mol/L) dilator was
      compared in 13 patients with angiographically documented coronary artery disease
      and in 7 patients with normal coronary angiograms. Vascular response was assessed
      by Doppler ultrasonography. Whereas the vascular responses to nitroglycerin in
      patients with abnormal and normal findings on coronary angiograms were similar,
      the responses to acetylcholine were clearly different. The ratio of mean blood
      flow velocity (+/-SD) measured during administration of acetylcholine 10-6 mol/L
      and mannitol was significantly lower in patients with abnormal versus normal
      results of coronary angiography (1.15 +/- 0.35 vs 2.20 +/- 1.06; p < 0.05). The
      vascular response to acetylcholine 10-5 mol/L in patients with an abnormal
      finding on their coronary angiogram was highly variable when compared with that
      in patients with normal results. Thus, in patients with angiographically proven
      coronary artery disease, the response of the peripheral circulation to
      acetylcholine is characterized by a great variability and a reduced sensitivity,
      when compared with that in patients with normal findings on coronary angiography.

PMID- 8546083
TI  - Measurement of parasympathetic activity from 24-hour ambulatory
      electrocardiograms and its reproducibility and sensitivity in normal subjects,
      patients with symptomatic myocardial ischemia, and patients with diabetes
      mellitus.
AB  - The parasympathetic nervous system plays a major role in the pathophysiology of
      many cardiovascular disease, particularly in modulating myocardial electrical
      stability. Measurements of heart rate variability have been widely used to assess
      parasympathetic activity. The reproducibility of measurements obtained from 24
      hour ambulatory electrocardiograms has not been well documented. We have
      developed a technique for measuring parasympathetic activity from clinical
      quality 24-hour ambulatory electrocardiograms by counting beat-to-beat increases
      in RR interval that are > 50 ms. To determine the reproducibility and sensitivity
      of our technique, we analyzed repeated 24-hour electrocardiograms of 173 subjects
      (19 normal subjects, 67 patients with ischemic heart disease, and 87 diabetics)
      followed up over periods of 2 to 16 weeks. In all subject groups, mean values for
      repeated measurements were virtually identical. Measurements were stable in all 3
      groups throughout the course of the study, as assessed by intraclass correlation
      coefficients. This technique is sensitive enough to detect relatively small
      changes in parasympathetic activity in subjects, as demonstrated by the
      calculated Bland and Altman coefficients of repeatability. Reproducibility and
      sensitivity of our technique are particularly good in normal subjects and in
      patients with ischemic heart disease. The results obtained with this technique
      imply that other related measurements of parasympathetic activity will show
      similar excellent short- and long-term reproducibility and sensitivity.

PMID- 8546084
TI  - Predictors of physical activity in patients with chronic heart failure secondary
      to either ischemic or idiopathic dilated cardiomyopathy.
AB  - To identify predictors of physical activity levels in patients with chronic heart
      failure, 43 patients, aged 33 to 91 years, who had well-compensated heart failure
      were asked to perform a symptom-limited exercise treadmill test and to complete
      activity logs for 2 consecutive days while wearing an ambulatory heart rate
      activity monitor. Activity logs included information on the type of activity,
      duration, rating of perceived exertion, symptoms experienced, and the intensity
      of symptoms. Subjects also completed the Duke Activity Status Index, a brief self
      administered questionnaire that assesses physical functioning, and a self
      efficacy for general activity questionnaire. Simultaneous multiple regression
      analysis was used to predict physical activity levels from a model that included:
      personal variables of physical fitness (peak oxygen consumption); knowledge,
      attitudes, and beliefs including self-efficacy for general activity, and rating
      of perceived exertion during daily activity; and environmental factors such as
      social support (marital status). The overall model explained 38% of the variance
      (p < 0.001). Self-efficacy (p = 0.015) was the strongest predictor of physical
      activity in this group. From this initial descriptive study, we conclude that
      self-efficacy is a better predictor of performance of physical activity than
      measures of physical fitness or rating of perceived exertion during activity.
      Additional studies are needed to examine other behavioral and physiologic
      mediators as well as behavioral strategies that may be used to increase
      participation in physical activity programs. Particularly promising are
      strategies to enhance self-efficacy for exercise.

PMID- 8546085
TI  - Comparison of cleft and papillary muscle position in cleft mitral valve and
      atrioventricular septal defect.
AB  - Differentiation of cleft mitral valve from atrioventricular septal defect (AVSD)
      is surgically important because of different conduction pathways. The purpose of
      this study was to find echocardiographic markers for differentiating cleft mitral
      valve from AVSD. We examined 11 children with cleft mitral valve, 11 children
      with AVSD, and 11 normal children. We defined a fixed reference point (0 degrees
      of arc) at the medial junction of the right ventricular free wall with the
      posteroinferior ventricular septum. Left ventricular papillary muscle and cleft
      position was measured clockwise in degrees of arc from 0 degrees around a point
      representing the center of the left ventricle in the parasternal short-axis
      views. Mural leaflet size was expressed by the arc between the bases of the
      papillary muscles. Papillary muscle position in cleft mitral valve was similar to
      that in normals (anterolateral ventricular papillary muscle:cleft mitral valve
      194 +/- 10 degrees, normals 191 +/- 8 degrees; posteromedial ventricular
      papillary muscle:cleft mitral valve 329 +/- 10 degrees, normals 329 +/- 14
      degrees). In AVSD, both left ventricular papillary muscles originated closer to
      each other and were rotated counterclockwise (anterolateral papillary muscle: 182
      +/- 7 degrees; posteromedial papillary muscle: 287 degrees +/- 17 degrees). The
      mural leaflet size was similar in cleft mitral valve and in normal children. In
      AVSD, the mural leaflet was significantly smaller than in cleft mitral valve and
      in normals. The cleft position did not permit distinction between cleft mitral
      valve and AVSD. In conclusion, echocardiographic measurements of papillary muscle
      position and mural leaflet size permit differentiation of cleft mitral valve from
      AVSD.

PMID- 8546086
TI  - Reduction in lymphocyte beta-adrenergic receptor density in infants and children
      with heart failure secondary to congenital heart disease.
AB  - To identify changes in catecholamine levels and beta-adrenergic receptor density
      in children with varying degrees of congestive heart failure, we measured plasma
      norepinephrine (NE), epinephrine, and beta-adrenergic receptor levels in 91
      noncyanotic patients using high-performance liquid chromatography and a
      radioligand binding assay. Plasma NE levels in 41 patients with heart failure
      (694 +/- 236 pg/ml) were significantly higher than those in 50 patients without
      it (274 +/- 68 pg/ml, p < 0.001). In addition, beta-adrenergic receptor density
      was significantly lower in patients with heart failure (0.81 +/- 0.48 fmol/10(6)
      cells) than in those without it (2.43 +/- 1.09 fmol/10(6) cells, p < 0.001), but
      epinephrine levels were not significantly different between the 2 groups. The
      receptor reduction in heart failure correlated well with elevated plasma NE
      levels (r = -0.60, p < 0.001). The degree of left to right shunt flow and
      pulmonary systolic pressure correlated directly with plasma NE levels and
      inversely with beta-adrenergic receptor density. From the best compromise between
      sensitivity and specificity, the optimal cutoff point for heart failure was > 390
      ng/ml for NE and < 1.30 fmol/10(6) cells for beta-adrenergic receptor density,
      respectively. A follow-up study in 15 of 30 patients with heart failure after
      surgery showed a significant decrease in plasma NE and an increase in beta
      adrenergic receptor density. Changes in plasma NE levels and beta-adrenergic
      receptor density occur concurrently with clinical symptoms of heart failure and
      may be used as indexes for assessing the presence and severity of heart failure
      in infants and children.

PMID- 8546087
TI  - Evaluation using dobutamine stress echocardiography in patients with insulin
      dependent diabetes mellitus before kidney and/or pancreas transplantation.
AB  - The purpose of this study was to examine the ability of dobutamine stress
      echocardiography to stratify patients with juvenile onset, insulin-dependent
      diabetes mellitus who are being considered for kidney and/or pancreas
      transplantation, into high-or low-risk groups for future cardiac events. Fifty
      three such patients underwent dobutamine stress echocardiography before kidney
      and/or pancreas transplantation. Cardiac events, including cardiac death,
      nonfatal myocardial infarction, unstable angina, pulmonary edema, and need for
      coronary revascularization, occurring between the time of the dobutamine stress
      echocardiogram and the last patient follow-up contact were retrospectively
      identified. Twenty patients 938%) had an abnormal dobutamine stress
      echocardiogram. Eleven patients had 15 cardiac events over a mean (+/- SD) follow
      up period of 418 +/- 269 days. Event rates were 45% among those with an abnormal,
      versus 6% among those with a normal dobutamine stress echocardiogram (p = 0.002).
      The result of the dobutamine stress test independently predicted prognosis in a
      multivariate analysis (p = 0.003, odds ratio = 12.7). We conclude that dobutamine
      stress echocardiography accurately stratifies patients with juvenile onset,
      insulin-dependent diabetes being considered for kidney and/or pancreas
      transplantation for risk of future cardiac events.

PMID- 8546088
TI  - Reinnervation of the transplanted human heart as evidenced from heart rate
      variability studies.
AB  - This study evaluated heart rate variability (HRV) after cardiac transplantation
      in humans in an attempt to test the hypothesis that cardiac reinnervation occurs
      in the post-transplant period. HRV was measured using 24-hour Holter recordings
      performed on 37 ambulant patients 1 to 122 months after cardiac transplantation.
      All patients were free of histologic rejection and were taking no medication
      likely to influence HRV. Time and frequency domain were analyzed and circadian
      rhythm of hourly average heart rate was calculated. HRV increased with time after
      the transplant. Compared with patients in the early post-transplant period,
      patients > 36 months after transplant had lower 24-hour heart rates (86 vs 93
      beats/min), an increased average of all 5-minute SDs of NN intervals (17.6 vs
      11.3), and higher low-and high-frequency power. Ten of the 27 patients > 3 years
      after transplantation had evidence of functional cardiac reinnervation. Compared
      with patients who had no reinnervation, these patients had increased circadian
      variability with lower nocturnal heart rates (76 vs 91 beats/min) and greater
      sympathetic activity during daytime (natural logarithm sympathetic power -0.36 vs
      -1.45) and nighttime (natural logarithm sympathetic power -0.43 vs -1.98).
      Despite lower nocturnal heart rates, there was no HRV evidence for an increase in
      parasympathetic activity. Thus, patients late after cardiac transplantation have
      HRV evidence for an increase in sympathetic control of the heart.

PMID- 8546089
TI  - Hemodynamic correlates of spontaneous echo contrast in the descending aorta.
AB  - To identify the hemodynamic association of spontaneous echo contrast (SEC) in the
      descending aorta (DA), we measured aortic flow parameters in 102 consecutive
      patients studied with transesophageal echocardiography. SEC in the DA was
      identified in 19 of 102 patients (19%). Patients with SEC in the DA were older
      (67 +/- 9 vs 57 +/- 17 years; p = 0.001), had a higher proportion of chronic
      atrial arrhythmia (13 of 19 vs 11 of 83; p = 0.000001), and had a higher
      frequency of decreased left ventricular performance (10 of 19 vs 19 of 83; p =
      0.01). Patients with SEC in the DA had larger aortic diameters (2.9 +/- 0.5 vs
      2.3 +/- 0.4 cm; p = 0.0001), lower maximal velocity in the DA (42.6 +/- 12.8 vs
      75.6 +/- 34.4 cm/s; p = 0.0001), and lower maximal shear rate (61.6 +/- 20.3 vs
      139.9 +/- 78.8 s-1; p = 0.0001). There was no difference in volumetric flow in
      the DA between groups. In multivariate analysis, only arrhythmia (p = 0.008) and
      maximal shear rate (p = 0.002) were identified as significant independent
      predictors of SEC in the DA. We conclude that SEC in the DA is related to chronic
      atrial arrhythmia and shear rate but not to volumetric flow.

PMID- 8546090
TI  - Accuracy and usefulness of atrial pacing in conjunction with transthoracic
      echocardiography in the detection of cardiac ischemia.
AB  - Transthoracic echocardiography combined with transesophageal atrial pacing was
      performed in a community outpatient setting and compared with single-photon
      emission computed tomography (SPECT) and with coronary arteriography to determine
      the accuracy and usefulness of the technique. Two groups were defined: group A
      consisted of 65 of 189 patients who underwent all 3 procedures within a 90-day
      period; group B consisted of 53 patients who had atrial pacing with transthoracic
      echocardiography. Seventy-one patients had previously undergone atrial pacing
      with simultaneous transesophageal echocardiography. Atrial pacing to induce
      abnormal wall motion as an indicator of ischemia was performed by increasing the
      double product to > 20,000. We obtained a sensitivity and specificity of 87% and
      88% for group A and 72% and 80% for group B, respectively. We believe that
      transthoracic echocardiography with atrial pacing is indicated as a means of
      stress echocardiography in its own right, especially in nonambulatory and
      chronotropically incompetent patients, as well as in the presence of an ambiguous
      result on SPECT testing. It is highly accurate compared with our previous study
      with atrial pacing and simultaneous transesophageal echocardiography, better
      tolerated, more easily accepted, less invasive, and less costly. Thus, it is a
      useful stress modality in the detection of myocardial ischemia.

PMID- 8546091
TI  - Coronary calcium as a reliable tool for differentiating ischemic from nonischemic
      cardiomyopathy.
AB  - In conclusion, the presence or absence of coronary calcium as detected by this
      rapid technique represents a simple and reliable noninvasive sign for the
      differential diagnosis between ischemic and nonischemic DC.

PMID- 8546092
TI  - Combined isoproterenol and epinephrine for the resuscitation of patients with
      cardiac asystole secondary to coronary artery disease.
AB  - In summary, the use of isoproterenol as an adjuvant to epinephrine in asystolic
      patients may increase the likelihood of return of spontaneous circulation.

PMID- 8546093
TI  - Costs of coronary restenosis (Lovastatin Restenosis Trial).
AB  - Within the Lovastatin Restenosis Trial, restenosis has been clearly shown to
      increase resource utilization and costs. While it is not possible to generalize
      these results to other patient populations, it is clear that successful efforts
      to decrease restenosis will certainly improve efficacy while decreasing follow-up
      costs and increasing the cost-effectiveness of intervention in the coronaries.

PMID- 8546094
TI  - Prognosis of patients with severe left ventricular dysfunction after coronary
      artery bypass grafting.

PMID- 8546095
TI  - Insulin-like growth factor-I and angiographically documented coronary artery
      disease.
AB  - In conclusion, we have reported an association between low IGF-I concentrations
      and CAD in relatively young men. This observation raises the possibility that IGF
      I deficiency could be part of the polymetabolic syndrome. Whether a subnormal IGF
      I production is due to growth hormone secretory abnormalities or to other
      metabolic reasons (e.g., insulin resistance or fat distribution, or both) is
      still unknown.

PMID- 8546096
TI  - Comparison of cycle lengths between induced and spontaneous sustained ventricular
      tachycardia during concordant antiarrhythmic therapy associated with healed
      myocardial infarction.
AB  - We propose that in clinical practice, whenever possible, the VT detection
      interval should be selected by adding >60 ms to the induced maximal VT cycle
      length in order to ensure a high sensitivity for the detection of future
      spontaneous VT episodes.

PMID- 8546097
TI  - Effects of atrial fibrillation and atrial flutter on the signal-averaged
      electrocardiogram.
AB  - In conclusion, atrial flutter can create significant errors in the automated time
      domain analysis of the SAECG that are only apparent when the study is repeated in
      sinus rhythm, thus lowering the predictive accuracy of the technique in patients
      with atrial flutter. Atrial fibrillation rarely creates problems with time-domain
      analysis of the SAECG. These findings suggest that, unless the performance of a
      specific signal-averaging device has been evaluated in patients with atrial
      flutter and found to have acceptable error rates, patients with atrial flutter
      should not have SAECGs performed for postinfarction risk assessment.

PMID- 8546098
TI  - New forceps delivery technique for coil occlusion of patent ductus arteriosus.
AB  - We remain very enthusiastic about transcatheter coil occlusion of the PDA.
      However, surgical ligation has been performed successfully and with relatively
      low risk of complications. Therefore, an alternative nonsurgical technique must
      demonstrate comparable success and safety. We believe that this new forceps
      delivery technique has significant advantages over previously reported PDA coil
      occlusion techniques and should warrant further clinical investigation.

PMID- 8546099
TI  - Comparison of simultaneous Doppler- and catheter-derived right ventricular dP/dt
      in hypoplastic left heart syndrome.
AB  - Doppler estimation of RV dP/dt correlates well with micromanometer catheter
      measured values in children with hypoplastic left heart syndrome. Doppler
      estimation of RV dP/dt is a method of quantifying RV systolic function
      independent of geometric assumptions, and may be a valuable method for
      longitudinal analysis of RV function.

PMID- 8546100
TI  - Aortic dissection with flap prolapse into the left ventricle.
AB  - Transesophageal echocardiography provided an accurate diagnosis of intimal flap
      prolapse into the left ventricle in all 6 of our patients. This complication of
      AD is a newly recognized and uncommonly discerned cause of severe AR.

PMID- 8546101
TI  - In vitro quantification of radiofrequency ablation lesion size using intracardiac
      echocardiography in dogs.
AB  - The results of this study demonstrate that real-time ultrasonic evaluation of
      radiofrequency lesion creation and lesion size is feasible.

PMID- 8546102
TI  - Effect of aging from infancy to childhood on flow velocity patterns of pulmonary
      vein by Doppler echocardiography.
AB  - This study demonstrated the age-related changes in pulmonary venous flow
      velocities during 36 months of life. These results suggest that age-related
      changes in the D and S wave reflect the maturational or developmental alterations
      in both LV and left atrial diastolic properties, especially during the relaxation
      process.

PMID- 8546103
TI  - Cost versus charge: another look.

PMID- 8546104
TI  - Cost of lipid-lowering statin drugs.

PMID- 8546105
TI  - Patients with left circumflex coronary-related acute myocardial infarction
      without ST-segment elevation who benefit from reperfusion therapy: the problem is
      to identify them.

PMID- 8546106
TI  - Plasma coagulation factors are also non-lipid coronary heart disease risk
      factors.

PMID- 8546107
TI  - In search of altruistic community: patterns of social support mobilization
      following Hurricane Hugo.
AB  - Twelve months after Hurricane Hugo, 1,000 disaster victims and nonvictims were
      asked about social support they exchanged following the hurricane. Victims of
      disaster received and provided very high levels of tangible, informational, and
      emotional support. Disaster exposure (loss and harm) was a strong predictor of
      help received and a modest predictor of help provided. However, postdisaster help
      was not distributed equally and disaster exposure was more strongly related to
      social support in some groups than in others. Race, education, and age most
      consistently moderated the impact of disaster exposure on receipt of postdisaster
      support. Blacks and less educated victims received less help than similarly
      affected victims who were white or more educated. Relative disadvantage of being
      old in receiving support was not the case for those elderly disaster victims who
      experienced threats to their lives or health. Some subgroups of victims were
      relied upon disproportionately for providing assistance. Implications for social
      support research are addressed.

PMID- 8546108
TI  - Effects of parental alcoholism and life stress on Hispanic and Non-Hispanic
      Caucasian adolescents: a prospective study.
AB  - Investigated ethnicity and parental alcoholism as factors that might influence
      the stress vulnerability of adolescents. It extended an initial cross-sectional
      study of this same sample by adding two annual assessments which allowed for
      additional cross-sectional analyses and longitudinal tests. Hispanic and
      Caucasian adolescents (N = 306 at Time 1) completed measures of their own life
      stress, family conflict, and alcohol use. Their parents reported on adolescents'
      internalizing and externalizing symptoms. Cross-sectional analyses at Time 2, and
      prospective analyses involving Time 1 and Time 2 measures were, for the most
      part, consistent with the original study's results. Caucasian adolescents and
      children of alcoholic parents appeared to be more vulnerable to stress than
      Hispanic adolescents and children of nonalcoholic parents. Family conflict was a
      partial explanation for this increased vulnerability.

PMID- 8546109
TI  - Public knowledge, attitudes, and beliefs about homeless people: evidence for
      compassion fatigue.
AB  - Media reports suggest that the public is becoming impatient with the homeless-
      that so-called "compassion fatigue" has gripped the nation. This characterization
      of public sentiment could have important policy consequences-- restrictive
      measures can be justified by growing public impatience, and progressive housing
      policies seem feasible within a hostile climate of opinion. But evidence to
      support the compassion fatigue notion is anecdotal. We examine the issue by
      tracking the results of public opinion polls and by reporting detailed evidence
      from a nationwide random-digit dial telephone survey (N = 1,507) concerning
      knowledge attitudes and beliefs about homeless people. To be sure, the public
      sees homelessness as an undesirable social problem and wants something done about
      it. However, although the homeless are clearly stigmatized, there is little
      evidence to suggest that the public has lost compassion and is unwilling to
      support policies to help homeless people.

PMID- 8546110
TI  - Estimating rates of chronic fatigue syndrome from a community-based sample: a
      pilot study.
AB  - Most of the Chronic Fatigue Syndrome (CFS) epidemiological studies have relied on
      physicians who refer patients having at least six months of chronic fatigue and
      other symptoms. However, there are a number of potential problems when using this
      method to derive prevalence statistics. For example, some individuals with CFS
      might not have the economic resources to access medical care. Other individuals
      with CFS might be reluctant to use medical personnel, particularly if they have
      encountered physicians skeptical of the authenticity of their illness. In
      addition, physicians that are skeptical of the existence of CFS might not
      identify cases. In the present pilot study, a random community sample (N = 1,031)
      was interviewed by telephone in order to identify and comprehensively evaluate
      individuals with symptoms of CFS and those who self-report having CFS. Different
      definitions of CFS were employed, and higher rates (0.2%) of CFS were found than
      in previous studies. Methodological benefits in using more rigorous
      epidemiological methods when estimating CFS prevalence rates are discussed.

PMID- 8546111
TI  - Los Angeles study of residential magnetic fields and childhood brain tumors.
AB  - A measurement study of residential magnetic fields and brain tumors in children
      that was added onto an ongoing case-control interview study in Los Angeles
      County, California, include 298 children under age 20 years with a primary brain
      tumor diagnosed from 1984 to 1991 and 298 control children identified by random
      digit dialing. Magnetic fields were determined for all Los Angeles homes where
      these 596 children lived from conception to diagnosis (1,131 homes) by mapping
      and coding the wiring configurations outside the home and by taking a series of
      exterior spot and profile measurements. In addition, for a subset of subjects
      (35%; 211 homes) 24-hour measurements were taken in the child's room and one
      other room. Although measured fields are consistently highest in the highest of
      the five wire code categories, fields in homes in this category are much lower in
      Los Angeles than in Denver, where the code originated. Brain tumor risk appears
      not to relate to measured fields inside (p for trend for child's room = 0.98) or
      outside (p for trend for front wall = 0.82) the home. An apparent increase in
      risk among children living at diagnosis in homes with underground wiring appears
      to be an artifact introduced by using current controls for historical cases
      because this apparent excess risk disappeared in an analysis restricted to the
      later years of the study when cases and controls were accrued concurrently. Our
      study does not show an overall association of pediatric brain tumors with
      measured fields, with "very high" wiring configurations, or with any of several
      other potential sources of exposure, such as use of various electrical
      appliances, but the prevalence of high fields (> 2 mG) and very high fields (> 3
      mG) in Los Angeles homes was too low to detect a moderate effect of the magnitude
      reported in other studies.

PMID- 8546112
TI  - Childhood brain tumor occurrence in relation to residential power line
      configurations, electric heating sources, and electric appliance use.
AB  - To assess the relation between childhood brain tumor occurrence and exposure to
      potential sources of residential magnetic fields, a population-based case-control
      study of incident brain tumors was conducted in the Seattle, Washington, area at
      the Fred Hutchinson Cancer Research Center from 1989 to 1994 among children
      younger than age 20 years who were diagnosed from 1984 to 1990. The specific aims
      were to evaluate whether proximity to high-current residential power lines, as
      defined by the Wertheimer-Leeper code, or use of electric appliances or electric
      heating sources by the mother while pregnant or by the child before diagnosis
      were associated with increased risks of brain tumor occurrence. The mothers of
      133 cases and 270 controls (recruited by random digit dialing) participated. Risk
      of brain tumor occurrence did not increase with increasing exposure, as indicated
      by the five-level Wertheimer-Leeper code. When exposure was dichotomized as high
      versus low, the odds ratio was 0.9 (95% confidence interval 0.5-1.5) and did not
      vary significantly by sex, age, or histology. No elevations in risk were found
      for ever versus never use of electric blankets, water beds, or electric heating
      sources. Odds ratios were slightly elevated for nine appliances and were at or
      below 1.0 for eight others. These data do not support the hypothesis that
      exposure to magnetic fields from high-current power lines, electric heating
      sources, or electric appliances is associated with the subsequent occurrence of
      brain tumors in children.

PMID- 8546113
TI  - Invited commentary: evolution of epidemiologic evidence on magnetic fields and
      childhood cancers.

PMID- 8546114
TI  - Cohort study of Air Canada pilots: mortality, cancer incidence, and leukemia
      risk.
AB  - Despite the special working environment and exposures of airline pilots, data on
      risk of death and cancer incidence in this occupational group are limited. The
      authors investigated a cohort of 2,740 Air Canada pilots who contributed 62,449
      person-years of observation. All male pilots employed for at least 1 year on and
      since January 1, 1950, were studied. The cutoff date for outcome information was
      December 31, 1992. Standardized mortality ratio (SMR) and standardized incidence
      ratio (SIR) were used to compare mortality rates and cancer incidence rates of
      the cohort with the respective Canadian population rates. Ninety percent
      confidence intervals of the SMR and SIR were calculated. Statistically
      significant decreased mortality was observed for all causes (SMR = 0.63, 90%
      confidence interval (CI) 0.56-0.70), for all cancers (SMR = 0.61, 90% CI 0.48
      0.76), and for all noncancer diseases (SMR = 0.53, 90% CI 0.45-0.62). Mortality
      from aircraft accidents was significantly raised (SMR = 26.57, 90% CI 19.3-35.9).
      Significantly decreased cancer incidence was observed for all cancers (SIR =
      0.71, 90% CI 0.61-0.82), rectal cancer (SIR = 0.42, 90% CI 0.14-0.96), lung
      cancer (SIR = 0.28, 90% CI 0.16-0.46), and bladder cancer (SIR = 0.36, 90% CI
      0.12-0.82). Prostate cancer (SIR = 1.87, 90% CI 1.38-2.49) and acute myeloid
      leukemia (SIR = 4.72, 90% CI 2.05-9.31) were significantly increased. The
      preferred relative risk model for radiation-induced nonchronic lymphoid leukemia
      (Beir V report) was applied to the cohort by using published estimates of in
      flight radiation exposures. The estimated relative risk ranged from 1.001 to 1.06
      and did not differ significantly from the observed SIR (SIR = 1.88, 90% CI 0.80
      3.53). However, the incidence rate of acute myeloid leukemia was significantly
      increased. Monitoring of in-flight radiation exposure and long-term follow-up of
      civil aviation crew members is needed to further assess cancer incidence and
      leukemia risk in this special occupational group.

PMID- 8546115
TI  - Employment and coronary risk in women at midlife: a longitudinal analysis.
AB  - This study investigated the relation between employment and cholesterol in 541
      women aged 42-50 years who resided in Allegheny County, Pennsylvania, in 1985
      1988. Employment, health-related variables, and cholesterol were assessed at
      baseline and 3 years later. At baseline, employed and nonemployed women did not
      differ in cholesterol or health behaviors. However, women employed at baseline
      had a significant decrease in total high density lipoprotein cholesterol (1.9
      mg/dl) and high density lipoprotein2 cholesterol subfraction (3.2 mg/dl) at
      follow-up. Those who were employed at both assessments had the lowest high
      density lipoprotein cholesterol at follow-up. These effects could not be
      accounted for by sociodemographics or employment quality variables. Post hoc
      analyses were conducted to examine health behaviors as a potential mechanism to
      account for the association between employment status and cholesterol. Over the
      study period, those who were employed at baseline were less likely to increase
      exercise and more likely to gain weight than those who were not employed at
      baseline. With menopause-related changes in metabolism, this can result in
      detrimental effects for cholesterol levels and coronary health. The results
      highlight the importance of longitudinal assessment in the study of employment
      and health.

PMID- 8546116
TI  - Total and high density lipoprotein cholesterol as risk factors for coronary heart
      disease in elderly men during 5 years of follow-up. The Zutphen Elderly Study.
AB  - The associations of serum total and high density lipoprotein (HDL) cholesterol
      with coronary heart disease were investigated in men aged 64-84 years from the
      Dutch town of Zutphen during 5 years of follow-up. In 1985, 885 randomly selected
      men, 710 of whom did not have a history of clinical coronary heart disease,
      participated in the study. Associations were adjusted for age, body mass index,
      systolic blood pressure, cigarette smoking, and alcohol consumption. Total
      cholesterol was not significantly associated with the incidence of coronary heart
      disease, but for mortality the relative risk corresponding to a 1.00 mmol/liter
      increase was 1.40 (95 percent confidence interval (CI) 1.07-1.83). HDL
      cholesterol was not associated with mortality from coronary heart disease. The
      relative risk for the incidence of the disease, corresponding to a 0.26
      mmol/liter increase, was 0.80 (95 percent CI 0.60-1.08). For the ratio of HDL
      cholesterol to total cholesterol, the relative risk for coronary heart disease
      incidence corresponding to a 0.05 increase amounted to 0.70 (95 percent CI 0.51
      0.95). These results show that in elderly men followed for 5 years, both total
      and HDL cholesterol are important in predicting coronary heart disease. Total
      cholesterol seems to be a stronger risk factor for mortality from the disease,
      whereas HDL cholesterol is more strongly associated with the incidence of a first
      coronary heart disease event.

PMID- 8546117
TI  - Association of sex hormones and adiposity with plasma levels of fibrinogen and
      PAI-1 in postmenopausal women.
AB  - Blood levels of the clotting factor fibrinogen and tissue plasminogen activator
      inhibitor-1 (PAI-1), a primary inhibitor of fibrinolysis, have been positively
      linked to risk of coronary heart disease. The authors have reported previously
      that plasma fibrinogen appears to rise after menopause and to be reduced with use
      of postmenopausal hormonal therapy. There is also evidence to suggest that sex
      hormones may influence PAI-1. To examine whether plasma fibrinogen and PAI-1
      antigen levels differ among older postmenopausal women according to use of
      hormone therapy and by blood level of estrogen and androgens, these variables
      were assessed among 277 healthy women aged 65-82 years, one half of whom were
      receiving therapy. The study population was drawn from the Study of Osteoporotic
      Fractures, Pittsburgh, Pennsylvania, during 1986-1988. Overall, results showed
      median PAI-1 levels to be lower on average with oral and transdermal use of
      hormone therapy (25.0 vs. 33.5 ng/ml, p < 0.01) and mean fibrinogen levels to be
      lower (279 vs. 295 mg/dl, p < 0.02) with use of oral estrogen (but not
      transdermal) therapy compared with women not receiving therapy. Among women not
      receiving therapy, PAI-1 and fibrinogen levels were not related to endogenous sex
      hormone levels, with the exception of a modest positive relation between PAI-1
      and serum estrone concentrations (rs = 0.29). In addition, a markedly higher PAI
      1 level was found for women with a preponderance of upper body fat, independent
      of obesity. In sum, results showed that older women receiving postmenopausal
      hormone therapy had more favorable plasma levels of the hemostatic factors PAI-1
      and fibrinogen than did those not receiving therapy, which can be explained in
      large part by differences between the two groups in obesity and body fat
      distribution.

PMID- 8546118
TI  - Seasonality in the clinical onset of insulin-dependent diabetes mellitus in
      Finnish children. Childhood Diabetes in Finland (DiMe) Study Group.
AB  - Seasonal patterns in the incidence of insulin-dependent diabetes based on 2,062
      cases diagnosed at age 14 years or under in Finland are described for the years
      1987-1992. Seasonal patterns were estimated presenting the data as short Fourier
      series up to three harmonics together with a possible linear trend. This method
      allows an arbitrary shape for the seasonal effect. Likelihood ratio tests and
      Akaike's information criterion were used to determine the number of harmonics
      necessary to model the seasonal pattern and to test differences among age- and
      sex-specific subgroups in the population. Seasonal patterns in incidence were
      compared between sexes and between the three 5-year age groups with each
      controlling for the other's effect. A significant seasonal pattern in the
      incidence of insulin-dependent diabetes was found for the sexes combined and for
      two age groups (0-9 and 10-14 years). A statistically significant seasonal
      pattern could be confirmed for males, but not for females. During a calendar
      year, one cycle with a decreased incidence of insulin-dependent diabetes in June
      was found among younger boys. Among older boys, there were two distinct cycles
      with a decreased incidence, the first in June and the second during November
      December. The most visible seasonal pattern was a lower number of cases diagnosed
      in June, while during the rest of the year the incidence remained relatively
      stable and high. The average annual incidence was 35.6 per 100,000 persons
      without any upward peaks.

PMID- 8546119
TI  - Reliability of alcohol intake as recalled from 10 years in the past.
AB  - The authors assessed the reliability of alcohol intake as recalled from 10 years
      in the past in a cohort of 2,907 US adults. Participants reported their drinking
      habits in the First National Health and Nutrition Examination Survey interview
      during 1971-1975. During a follow-up interview in 1982-1984, they were asked to
      recall their drinking habits 10 years earlier and to report their current habits.
      In general, the correlation for recalled alcohol intake versus reported intake at
      baseline was good (r = 0.7). For all subgroups stratified by race, sex,
      education, smoking status, and disease status, the age-adjusted correlations for
      recalled alcohol intake versus baseline intake were equal to or higher than those
      for current alcohol intake versus baseline intake. The reliability of recall of
      alcohol intake in the past differs among subgroups with different age and
      education levels. Recalled alcohol intake was also highly correlated with current
      alcohol intake; in particular, current heavier drinkers tended to underestimate
      their previous amount of drinking, an effect that was independent of other
      factors. These data suggest that although recalled alcohol intake is a better
      predictor of past intake than are reports of current intake, current drinking
      habits may be an important influencing factor in the estimation of alcohol intake
      as recalled from the distant past.

PMID- 8546121
TI  - Bias in case-control studies of screening effectiveness.
AB  - Screening programs, such as annual mammography, are undertaken to reduce
      mortality and/or morbidity from chronic diseases such as cancer. Matched case
      control studies have been used to assess the effectiveness of screening programs
      because of their relative simplicity and low cost. In such studies, the exposure
      history for controls consists of the number of screening examinations received
      prior to the date of diagnosis of the matched case. The authors know of no
      methodological evaluations that demonstrate the validity of such case-control
      studies. To examine the possible existence of bias due to design rules, the
      authors developed a simple deterministic model, which is used to calculate
      expected screening and disease patterns in a cohort. Cases and matched controls
      are selected from the cohort, and their screening histories are used to calculate
      an odds ratio, as is commonly done in practice. Results utilizing this simple
      model suggest that systematic inclusion of the examination from which diagnosis
      is made, which is the approach typically used in practice, leads to a positive
      bias (odds ratio > 1) in the absence of any real effect. Systematic exclusion of
      this examination appears to lead to a negative bias (odds ratio < 1). Although
      this simple approach has several limitations, the results suggest that a commonly
      used method of conducting case-control studies may yield biased odds ratios.
      Possible methods to reduce this bias may exist, such as defining exposure
      intervals differently.

PMID- 8546120
TI  - Duration of tick bites in a Lyme disease-endemic area.
AB  - Regression equations, based on scutal index (body length/scutal width), were
      developed to determine the duration of attachment for nymphal and adult female
      lxodes scapularis ticks. Feeding times were calculated for 444 nymphal and 300
      female ticks submitted by bite victims between 1985 and 1989 in Westchester
      County, New York, an area where Lyme disease is highly endemic. Nymphs were
      attached for a mean of 34.7 hours, with 26.8% removed after 48 hours, the
      critical time for transmission of Borrelia burgdorferi. Attachment times
      increased with victim age class (Kruskal-Wallis test, p < 0.05). Mean duration of
      attachment for female ticks (28.7 hours) was significantly less (Kruskal-Wallis
      test, p < 0.05) than that for nymphs, with 23.3% attached for more than 48 hours.
      The 0- to 9-year age class had the highest proportion (37.1%) of females attached
      for more than 48 hours. Nymphs remain attached to adult tick-bite victims longer
      than they remain attached to children. However, children have a high risk of
      acquiring Lyme disease because they receive more nymphal bites and also because
      they are less likely to have female ticks removed in time to prevent
      transmission.

PMID- 8546122
TI  - Negative bias in exposure-response trends in occupational studies: modeling the
      healthy workers survivor effect.
AB  - Many occupational studies analyze trends between cumulative exposure and
      mortality. The authors show that such trends are, in general, negatively
      confounded by employment status. Mortality rates for workers who leave work
      ("inactive" workers) are higher than for active workers because some workers
      leave because they are ill. The percentage of inactive relative to active person
      time is higher in low categories of cumulative exposure, causing employment
      status to act as a negative confounder of exposure-response trends (the opposite
      occurs for time-since-hire). We illustrate these phenomena using 10 "negative"
      mortality studies, in which adjustment for employment status removes false
      trends. However, adjustment for employment status will lead to biased estimates
      when it acts as an intermediate variable between cumulative exposure and death,
      as occurs directly when exposure causes a disabling disease that, in turn, causes
      death or indirectly when exposure causes workers to leave work. The authors
      illustrate this problem using simulated follow-up data for leaving, disease
      incidence, and mortality. In the null case in which cumulative exposure affects
      neither disease incidence (or mortality) nor leaving rates, employment status
      indeed acts as a negative confounder of exposure-response trends, and traditional
      adjustment eliminates this confounding. However, when cumulative exposure affects
      disease incidence or rates of leaving, adjustment for employment status will not
      be adequate. Employment status falls under the general rubric of variables that
      are simultaneously confounders and intermediate variables.

PMID- 8546123
TI  - Lipoprotein(a) in renal disease.
AB  - Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for
      atherosclerotic vascular disease. Several studies have described a correlation
      between high Lp(a) plasma levels and coronary heart disease, stroke, and
      peripheral atherosclerosis. In healthy individuals Lp(a) plasma concentrations
      are almost exclusively controlled by the apolipoprotein(a) [apo(a)] gene locus on
      chromosome 6q2.6-q2.7. More than 30 alleles at this highly polymorphic gene locus
      determine a size polymorphism of apo(a). There exists an inverse correlation
      between the size (molecular weight) of apo(a) isoforms and Lp(a) plasma
      concentrations. Average Lp(a) levels are high in individuals with low molecular
      weight isoforms and low in those with high molecular weight isoforms. Mean Lp(a)
      plasma levels are elevated over controls in patients with renal disease. Patients
      with nephrotic syndrome exhibit excessively high Lp(a) plasma concentrations,
      which can be reduced with antiproteinuric treatment. The mechanism underlying
      this elevation is unclear, but the general increase in protein synthesis caused
      by the liver due to high urinary protein loss is a likely explanation. Patients
      with end-stage renal disease (ESRD) also have elevated Lp(a) levels. These are
      even higher in patients treated by continuous ambulatory peritoneal dialysis than
      in those receiving hemodialysis. Lipoprotein(a) concentrations decrease to values
      observed in controls matched for apo(a) type following renal transplantation.
      This clearly demonstrates the nongenetic origin of Lp(a) elevation in ESRD. Both
      the increase in ESRD and the decrease following renal transplantation are apo(a)
      phenotype dependent. Only patients with high molecular weight phenotypes show the
      described changes in Lp(a) levels. In patients with low molecular weight types
      the Lp(a) concentrations remain unchanged during both phases of renal disease. As
      in the general population, Lp(a) is a risk factor for cardiovascular events in
      ESRD patients. In this patient group the apo(a) phenotype seems to be equally or
      better predictive of the degree of atherosclerosis than is Lp(a) concentration.
      Further prospective studies will be necessary to confirm these observations.
      Whether Lp(a) also plays a key role in the pathogenesis and progression of renal
      diseases needs further study. Controversial data on the role of the kidney in
      Lp(a) metabolism result from insufficient sample sizes of several studies. Due to
      the broad range and skewed distribution of Lp(a) plasma concentrations, large
      study groups must be investigated to obtain reliable results.

PMID- 8546124
TI  - Renal allograft and patient outcome after transplantation: pancreas-kidney versus
      kidney-alone transplants in type 1 diabetic patients versus kidney-alone
      transplants in nondiabetic patients.
AB  - Despite recent advances and improved outcome, pancreas transplantation remains
      controversial. The purpose of this review was to study renal allograft outcome
      after simultaneous pancreas-kidney transplants (SPK, n = 61), kidney-alone
      transplants in type I diabetic patients (KA-D, n = 63), and kidney-alone
      transplants in nondiabetic patients (KA-ND, n = 80). Patients were matched for
      donor age, donor gender, donor race, interval from donor admission to
      procurement, DR mismatch, and recipient gender. The mean renal allograft cold
      ischemic time and recipient age were lower in the SPK group. Patient survival was
      highest in the KA-ND group (99% and 86% at 1 and 5 years, respectively),
      intermediate in the SPK group (90% and 78% at 1 and 5 years, respectively), and
      lowest in the KA-D group (89% and 66% at 1 and 5 years, respectively) (P =
      0.004). similarly, renal allograft survival was higher in the KA-ND (89% and 63%
      at 1 and 5 years, respectively) and SPK (82% and 69% at 1 and 5 years,
      respectively) groups compared with the KA-D group (76% and 49% at 1 and 5 years,
      respectively) (P = 0.07). This difference disappeared when renal graft survival
      was censored for death, which probably reflects the selection bias. Actuarial
      pancreas graft survival was 76% and 62% at 1 and 5 years, respectively. Acute
      rejection (AR) was more frequent in the SPK group than in the KA-D and KA-ND
      groups (41% v 16% v 29%; P = 0.007). Delayed graft function (DGF), on the other
      hand, occurred more frequently in the KA-D group than in the KA-ND and SPK groups
      (66% v 55% v 38%; P = 0.08). Death as a result of a cardiovascular event occurred
      more frequently in the KA-D group. Cardiovascular death and renal graft failure
      occurred earlier in the SPK group. Cox regression analysis revealed a 1.6 and 1.8
      times higher risk of renal graft failure in the SPK group when the donor was > or
      = 40 years old or female and a five times higher risk of graft failure in the KA
      ND group in the presence of AR. Graft survival in patients with AR/DGF was lower
      than that in patients with no AR/no DGF in both the KA-D (71% and 63% v 100% and
      100% at 1 and 5 years, respectively; P = 0.03) and KA-ND (90% and 56% v 100% and
      100% at 1 and 5 years, respectively; P = 0.001) groups. Acute rejection did not
      affect graft survival in the SPK group. In the absence of AR, DGF had no effect
      on graft survival in any of the groups. Although the selection bias in favor of
      pancreas transplantation does not allow for definitive conclusions, our results
      show that outcome after SPK transplantation is acceptable and factors that
      influence the outcome after this procedure may be different from the ones
      affecting KA-D recipients.

PMID- 8546125
TI  - Serum albumin and mortality after renal transplantation.
AB  - The incidence, causes, and consequences of hypoalbuminemia after renal
      transplantation are not well defined. We examined clinical correlates of serum
      albumin measured at 3 months, 6 months, 1 year, and annually thereafter in 706
      renal transplant recipients who survived at least 6 months with a functioning
      allograft. Follow-up was 7.0 +/- 4.2 years. Hypoalbuminemia (< or = 3.5 g/dL) was
      most common at 3 months (31%, n = 692), least common at 1 year (12%, n = 656),
      and then became increasingly common among survivors, for example, 14% (n = 466)
      at 4 years, 20% (n = 204) at 8 years, and 29% (n = 77) at 12 years after
      transplantation. By multiple linear regression, variables that correlated (P <
      0.05) with lower serum albumin at 3, 6, 12, and 24 months included age, diabetes,
      proteinuria, and cytomegalovirus infection. Other independent correlates on at
      least one of these occasions included renal function and chronic disease
      (malignancy, liver disease, and cardiovascular disease). Serum albumin, as a time
      averaged and time-dependent covariate, was a strong independent risk factor for
      death using Cox proportional hazards analysis (relative risk for each g/dL
      increment, 0.26; 95% confidence interval, 0.16 to 0.44 [1.00 = no risk]). The
      effects of albumin on mortality were independent of age, diabetes, serum lipids,
      renal function, chronic liver disease, malignancies, and cardiovascular disease.
      The effects of albumin on mortality were evident even when the analysis was
      restricted to patients dying several years after albumin was measured. Thus,
      hypoalbuminemia is common and serum albumin is a strong independent risk factor
      for all-cause mortality after renal transplantation.

PMID- 8546126
TI  - Logical and statistical fallacies in the use of Cox regression models.
AB  - Time-dependent covariates are an essential data analysis tool for modeling the
      effect of a study factor whose value changes during follow-up. However, survival
      analysis models can yield conclusions that are contrary to the truth if such time
      dependent factors are not defined and used carefully. We outline some of the
      biases that can occur when time-dependent covariates are used improperly in a Cox
      regression model. For example, we discuss why one should almost never use a
      covariate that has been averaged over a patient's entire follow-up time as a
      baseline covariate. Instead, the baseline value should be used as a covariate, or
      the cumulative average up to each point in time should be used as a time
      dependent covariate. We also document why one should use time-dependent
      covariates with great caution in analyses when the evaluation of a baseline
      factor is the primary objective. Several simulated examples are given to
      illustrate the direction and magnitude of the biases that can result from not
      adhering to some basic assumptions that underlie all survival analysis
      methodologies.

PMID- 8546127
TI  - Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol
      ingestion: importance of the osmolal gap.
AB  - Ethylene glycol poisoning classically presents as a metabolic acidosis with an
      increased anion gap. Metabolism of ethylene glycol to organic acids, and
      increased production of lactate, are responsible for the increased gap. We report
      the case of an alcohol user who consumed ethanol and ethylene glycol
      concurrently, and presented without acidosis, with a normal anion gap. Several
      hours later, when his serum ethanol level had declined, he developed severe
      acidosis with an elevated anion gap. An increased osmolal gap, not accounted for
      by the serum ethanol level, proved to be an important clue to the diagnosis. In
      this patient, ingestion of ethanol inhibited the hepatic metabolism of ethylene
      glycol to organic acids, obscuring the diagnosis. In intoxicated alcohol users,
      even in the absence of metabolic acidosis, serum osmolality measurements and
      calculation of the osmolal gap may facilitate the rapid diagnosis of ethylene
      glycol poisoning.

PMID- 8546128
TI  - Acute renal failure associated with the retinoic acid syndrome in acute
      promyelocytic leukemia.
AB  - All-trans-retinoic acid is an effective agent to induce remission in patients
      with acute promyelocytic leukemia (APL). Unlike conventional chemotherapy, this
      drug exerts its effect by inducing differentiation of immature leukemic cells. A
      distinctive clinical syndrome characterized by fever, dyspnea, effusions, weight
      gain, and organ failure (the "retinoic acid syndrome") can occur during treatment
      with this drug. Postmortem studies have shown extensive organ infiltration by
      leukemic cells, and the early administration of corticosteroids can result in
      prompt resolution of symptoms. We describe a patient with APL in whom acute renal
      failure developed during treatment with all-trans-retinoic acid. Transient renal
      enlargement during a period of leukocytosis and a beneficial response to
      treatment with dexamethasone suggest that renal failure in this patient was
      probably related to the retinoic acid syndrome.

PMID- 8546129
TI  - Paecilomyces varioti peritonitis in patients on continuous ambulatory peritoneal
      dialysis.
AB  - Paecilomyces varioti infection is a rare cause of peritonitis in patients on
      continuous ambulatory peritoneal dialysis (CAPD). We report two patients who
      developed P varioti peritonitis complicating CAPD. The clinical features and
      microbiological data of seven other previously reported cases are reviewed.
      Approximately half of the patients had received multiple antibiotics before the
      onset of the peritonitis because of either bacterial peritonitis or exit site
      infection. There was no particular pattern of peritoneal dialysate cell count,
      which was characteristic in this fungal peritonitis. Although all patients
      survived, morbidity was high. All patients required antifungal chemotherapy and
      removal of peritoneal catheter for eradication of the organism. Amphotericin B
      was effective in most cases. Patients of all previously reported cases did not go
      back to peritoneal dialysis after removal of peritoneal catheters. A combination
      of oral flucytosine and itraconazole was successful in treating our two patients.
      Although we managed to resume CAPD in our two patients with good functional
      outcome, abscesses and adhesions were major problems rendering most patients from
      other series failing to return to CAPD after recovery.

PMID- 8546130
TI  - Clarithromycin-associated visual hallucinations in a patient with chronic renal
      failure on continuous ambulatory peritoneal dialysis.
AB  - Visual hallucinations are a rare event in chronic renal failure and not related
      to uremia per se. Unreported in the literature is visual hallucinations occurring
      in association with the new macrolide antibiotic, clarithromycin. We describe
      such a case in a patient with end-stage renal disease (ESRD) maintained on
      continuous ambulatory peritoneal dialysis (CAPD). The combination of a relatively
      high dose of clarithromycin in face of chronic renal failure in a functionally
      anephric patient, with underlying aluminum intoxication, may have facilitated the
      appearance of this neurotoxic side effect. It is important to understand the
      pharmacokinetics of medications in face of chronic renal failure, the possibility
      of drug interactions, and how these factors should help guide medication therapy
      in the ESRD patient.

PMID- 8546131
TI  - Rusty peritoneal dialysis fluid after intravenous administration of iron dextran.
AB  - Rusty-colored peritoneal dialysate fluid was observed after intravenous
      administration of iron dextran to a patient with peritonitis being treated with
      vancomycin and rifampicin. The discoloration gradually cleared over a 24-hour
      period. Analysis of the fluid demonstrated that the discoloration could not be
      explained by the presence of erythrocytes or free hemoglobin. Iron (52
      micrograms/dL) was detected in the fluid and decreased to undetectable levels as
      the discoloration cleared. Addition of iron dextran to an unused bag of
      peritoneal dialysis fluid to achieve an iron concentration of 52 micrograms/dL
      resulted in no discoloration. Addition of rifampicin at a clinically relevant
      serum concentration (10 micrograms/dL) to a different unused bag caused a light
      orange discoloration. Addition of iron dextran and rifampicin simultaneously in
      the concentrations mentioned to an unused bag caused a rusty discoloration almost
      as dark as that observed in our patient. We postulate, therefore, that a
      combination of iron and rifampicin caused the marked discoloration of our
      patient's peritoneal effluent.

PMID- 8546132
TI  - Endothelin in organ transplantation.
AB  - Solid organ allografts are often compromised by ischemia, acute rejection
      episodes associated with hemodynamic changes, and chronic rejection typically
      characterized by the development of obliterative vasculopathy, and in the case of
      the kidney, and glomerulosclerosis. Recent in vivo data indicate that endothelin
      (ET) production is locally upregulated in rejecting allografts, and that, in
      addition to endothelial cells, ET is also produced by graft-infiltrating
      mononuclear cells (monocytes/macrophages). In vitro data also indicate that ET
      production is regulated, at least in part, by certain T cell-and
      monocyte/macrophage-derived cytokines, which are abundant in rejecting
      allografts. These data and the findings of elevated plasma levels of ET after
      transplantation (in particular during rejection processes), the effects of
      immunosuppressive drugs (cyclosporine and tacrolimus in particular) on ET
      production, and the profound vasoconstrictive and mitogenic properties of this
      peptide suggest that endothelin may be involved in the initiation and propagation
      of posttransplantation complications; including systemic hypertension, acute
      allograft dysfunction, and perhaps most importantly, chronic allograft
      dysfunction. These observations provide the rational to use ET receptor
      antagonists to formally address the potential role of ET in these processes, and
      to develop therapeutic strategies that ameliorate or possibly prevent these
      complications.

PMID- 8546133
TI  - Analgesics and the kidney: summary and recommendations to the Scientific Advisory
      Board of the National Kidney Foundation from an Ad Hoc Committee of the National
      Kidney Foundation.

PMID- 8546134
TI  - Karyomegalic interstitial nephritis.

PMID- 8546135
TI  - Decrease of exercise-induced microalbuminuria in patients with type I diabetes by
      means of an angiotensin-converting enzyme inhibitor.
AB  - Taking into account both the importance of microalbuminuria (MA) as a predictive
      parameter of clinical nephropathy in diabetic patients and the efficiency of
      exertion to show and/or to increase MA in both diabetic patients and normal
      individuals, we studied 37 type I diabetic patients divided into two groups:
      group A, with no MA at rest (n = 19), and group B, with MA at rest (n = 18).
      Group C comprised 10 healthy volunteers as controls. Changes of basal MA during
      exercise and postexercise were studied in all three groups. Normotensive patients
      with no metabolic disorders, normal renal function, and no proteinuria underwent
      an ergometric test up to 600 kg. This test was repeated after the administration
      of 20 mg enalapril in a single daily dose for 60 days. Body weight, systolic and
      diastolic arterial pressure, creatinine, and creatinine clearance were determined
      and showed no significant variations either between groups or with treatment.
      Microalbuminuria was studied in the three groups with and without administration
      of enalapril throughout the 2 months of the study. Determinations were performed
      under conditions of rest, exercise, and postexercise. Mean baseline MA values +/-
      SEM were as follows: at rest, 5.22 +/- 0.49, 58.36 +/- 13.24, and 4.73 +/- 0.45
      micrograms/min for groups A, B, and C, respectively; with exercise, 15.19 +/-
      4.43, 74.70 +/- 14.89, and 16.76 +/- 4.62 micrograms/min for groups A, B, and C,
      respectively; and postexercise, 32.04 +/- 6.64, 253.15 +/- 63.88, and 9.23 +/-
      3.25 micrograms/min, respectively. The geometric means of the baseline to
      posttreatment MA ratio were as follows: at rest, 0.95, 1.59 (P < 0.01), and 1.03
      for groups A, B, and C, respectively; with exercise, 1.53 (P < 0.01), 1.91 (P <
      0.01), and 1.69 for groups A, B, and C, respectively; and postexercise, 2.94 (P <
      0.01), 3.24 (P < 0.01), and 1.03 for groups A, B, and C, respectively. In
      conclusion, in the early diagnostic suspicion of diabetic nephropathy, the
      screening of postexercise MA during an ergometric test could be of help.
      Treatment with enalapril decreased MA in diabetic groups A (no MA at rest) and B
      (MA at rest) during exercise and postexercise, and also decreased MA in group B
      while at rest.

PMID- 8546136
TI  - Abnormal permeability to proteins and glomerular lesions: a meta-analysis of
      experimental and human studies.
AB  - Whether abnormal protein traffic through the glomerular capillary is one of the
      possible causes of glomerular injury has been a matter of considerable
      controversy. Experimental and clinical evidence indicate an association between
      the two, and several explanations of potential pathophysiologic pathways are
      available that may explain protein-dependent forms of renal injury. However, none
      of the mechanisms suggested thus far have been definitely proven. A meta-analytic
      review was used to further explore the relationship between urinary protein
      excretion and glomerular injury in experimental and human proteinuric
      nephropathies. In experimental models a definite positive association (P <
      0.0001) was found between urinary protein excretion and glomerulosclerosis. The
      overall effect size d for this relationship was 2.36 (95% confidence interval,
      2.13 to 2.60), corresponding to a correlation coefficient of r = 0.76. Similarly,
      the correlation between albuminuria and glomerular sclerotic lesions was highly
      significant (overall d = 2.88; 95% confidence interval, 2.33 to 3.42; P < 0.0001;
      correlation coefficient, r = 0.82). In humans the meta-analytic correlation
      yielded analogous, although less striking, results (overall d = 0.58; 95%
      confidence interval, 0.43 to 0.73; P < 0.0001; correlation coefficient, r =
      0.28). In conclusion, meta-analysis of data from studies examining urinary
      protein excretion revealed a significant positive correlation with glomerular
      sclerosis in both experimental models and human diseases. This study supports the
      role of abnormal protein traffic through the glomerular capillary as one of the
      possible causes of renal injury. However, the strong relationship found does not
      necessary establish a cause-and-effect relationship.

PMID- 8546137
TI  - Evaluation of urine acidification by urine anion gap and urine osmolal gap in
      chronic metabolic acidosis.
AB  - To investigate the clinical significance of urine anion gap and urine osmolal gap
      as indirect markers of urine acidification in chronic metabolic acidosis, we
      evaluated urine ammonium (NH4+), net acid excretion (NAE), urine anion gap (Na(+)
      + K(+) - Cl-), and urine osmolal gap (urine osmolality - [2(Na(+) + K(+)) +
      urea]) in 24 patients with chronic renal failure (CRF), eight patients with
      classic distal renal tubular acidosis (dRTA), and eight NH4Cl-loaded normal
      controls (NCs). Urine NH4+ excretion was lower (P < 0.001) in the CRF (5.4 +/-
      0.6 mmol/d) and dRTA (19.2 +/- 2.7 mmol/d) patients than in the NCs (52.6 +/- 3.7
      mmol/d); NAE was also lower (P < 0.001) in the CRF (9.8 +/- 1.6 mmol/d) and dRTA
      (16.7 +/- 4.7 mmol/d) patients than in the NCs (79.4 +/- 4.7 mmol/d). Urine anion
      gap was higher (P < 0.001) in the CRF (24.7 +/- 2.2 mmol/L) and dRTA (36.7 +/-
      7.7 mmol/L) patients than in the NCs (-16.2 +/- 5.5 mmol/L). Urine osmolal gap
      was lower (P < 0.05) in the dRTA patients (129.7 +/- 17.0 mmol/L) than in the NCs
      (319.7 +/- 58.4 mmol/L). When the data from all subjects were pooled, urine anion
      gap correlated inversely with urine NH4+ (r = -0.70, P < 0.001) and with NAE (r =
      -0.83, P < 0.001), and urine osmolal gap correlated positively with urine NH4+ (r
      = 0.69, P < 0.01) and with NAE (r = 0.71, P < 0.05). We conclude that impaired
      urine acidification in CRF and dRTA patients is associated with an increase in
      urine anion gap and a decrease in urine osmolal gap, and that both urine anion
      gap and urine osmolal gap correlate well with NAE as well as with urine NH4+.

PMID- 8546138
TI  - Intraglomerular and interstitial leukocyte infiltration, adhesion molecules, and
      interleukin-1 alpha expression in 15 cases of antineutrophil cytoplasmic
      autoantibody-associated renal vasculitis.
AB  - In renal biopsy specimens from 15 patients with antineutrophil cytoplasmic
      autoantibody (ANCA)-associated renal vasculitis, the infiltrating intraglomerular
      and interstitial leukocytes were localized and the adhesion molecules
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) and the cytokine interleukin-1 alpha (IL-1 alpha) were studied by an
      immunohistochemical method. Intraglomerular leukocytes were mainly macrophages
      (13.46 +/- 9.29 cells/glomerular cross-section) and, to a lesser extent, T
      lymphocytes (4.61 +/- 2.81 cells/glomerular cross-section). Staining with VCAM-1,
      which was negative in the undamaged tufts, was strongly positive in necrotizing
      extracapillary lesions. Staining with ICAM-1 was also present in the damaged
      tufts, but its pattern was more diffuse. Intraglomerular IL-1 alpha was found in
      all biopsy specimens. Where the Bowman's capsule was not damaged, the
      periglomerular infiltrating cells were macrophages (42.6 +/- 25.2
      cells/glomerular cross-section) and T lymphocytes (51.06 +/- 33.0
      cells/glomerular cross-section). When there was a granulomatous lesion involving
      the glomerulus, the number of cells per granulomatous area revealed a massive
      number of CD45-positive leukocytes (345.83 +/- 237.47 cells/granulomatous
      lesion), many of them positive for activity markers (HLA-DR, IL-2R), adhesion
      molecules, and IL-1 alpha. Many activated cells were also present in interstitial
      areas of perivascular clusters of leukocytes, in which T lymphocytes (prevalently
      CD4+ cells) outnumbered the macrophages (331.55 +/- 207.85 cells/0.05 mm2 area v
      125.68 +/- 60.57 cells/0.05 mm2 area). Adhesion molecules and IL-1 alpha were
      found in both tubular and vascular areas in all biopsy specimens. Our data
      strongly support the involvement of both the adhesion molecules ICAM-1 and VCAM-1
      in the recruitment of intraglomerular leukocytes in renal vasculitis, indicate
      that VCAM-1 is a very good marker of necrotizing-extracapillary damage, and
      suggest its crucial connection with the macrophage recruitment in these
      vasculitic lesions. The presence of histochemically detectable levels of IL-1
      alpha in glomeruli, tubules, and vessels and on some inflammatory cells supports
      its involvement in the vasculitic lesions, probably by triggering a positive
      feedback that increases the damage.

PMID- 8546139
TI  - Carotid artery lesions in patients with nondiabetic chronic renal failure.
AB  - Atherosclerotic complications are the leading cause of death in chronic renal
      failure (CRF) patients. Therefore, we wished to investigate the prevalence of
      carotid artery lesions (CALs) in these subjects. Two groups were evaluated by
      high-resolution echo Doppler: group 1 included 103 patients (68 males and 35
      females) affected by nonnephrotic CRF and group 2 included 100 control subjects
      (60 males and 40 females). The prevalence of hypertension was 84% in both groups.
      The exclusion criteria included diabetes mellitus and symptoms of cerebrovascular
      disease. In the two groups we evaluated clinical history, physical examination,
      total cholesterol, triglycerides, fibrinogen, blood cell counts, blood urea
      nitrogen, creatinine, 24-hour proteinuria, and urine analysis. In group 1
      patients the following lipid profile parameters were also evaluated: low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a),
      ApoAI, ApoAII, and ApoB. Group 1 had higher triglycerides and fibrinogen than
      group 2. A lower body mass index was found in group 1 than in group 2. The
      prevalence of CALs was significantly higher in the CRF patients than in the
      control subjects (62% v 47%; P = 0.04). The difference between the two groups was
      more striking among normotensive patients (62% v 19%; P = 0.03). All CRF patients
      affected by peripheral arterial disease and 86% of those having coronary artery
      disease had associated CALs. In CRF patients the severity of CALs was positively
      correlated to age, white blood cell count, triglycerides, and fibrinogen.
      Nondiabetic CRF patients have a higher prevalence of carotid artery lesions than
      control subjects. Several factors besides hypertension, including lipids, blood
      coagulation, and leukocytes, could contribute to the accelerated atherosclerosis
      of CRF patients.

PMID- 8546140
TI  - Falsely elevated serum vancomycin concentrations in hemodialysis patients.
AB  - Fluorescence polarization immunoassay (FPIA) is the most widely used clinical
      vancomycin assay in the United States. Questions exist regarding the accuracy of
      this polyclonal assay in patients with end-stage renal disease (ESRD). While
      several studies have reported discrepancies in vancomycin serum concentrations
      determined by FPIA compared with other vancomycin assays, no study has
      investigated the accuracy of vancomycin serum concentrations determined by FPIA
      in patients with ESRD undergoing maintenance hemodialysis. Therefore, we compared
      the assay performance of FPIA and enzyme multiplied immunoassay technique (EMIT)
      in six subjects with ESRD receiving high-efficiency hemodialysis. Subjects
      underwent 6 consecutive weeks of hemodialysis treatment with a cellulose acetate
      dialyzer (CA210) and received 1 g vancomycin intravenously once weekly during the
      last hour of dialysis. Vancomycin serum concentrations were determined by both
      EMIT and FPIA methodologies. From the serum concentration results of both assays,
      vancomycin dosing recommendations were calculated to achieve a desired steady
      state peak concentration of 35 mg/L and trough concentration of 10 mg/L. Overall,
      vancomycin serum concentrations reported by FPIA were significantly higher than
      those reported by EMIT. The mean difference between assays in the peak serum
      concentrations at weeks 1, 4, and 6 was 7.5, 11.5, and 11.2 mg/L, respectively.
      The mean difference in trough serum concentrations at weeks 1, 4, and 6 was 4.2,
      6.2, and 5.2 mg/L, respectively. The FPIA overestimation of the EMIT values
      (calculated as FPIA-EMIT) varied widely among study subjects with a range of 0.0
      mg/L to 27.0 mg/L for peak serum concentrations and 0.0 mg/L to 12.8 mg/L for
      trough serum concentrations. The mean doses calculated based on FPIA results were
      significantly lower than the EMIT-derived doses. No significant difference was
      observed in the calculated dosing intervals. These results demonstrate that FPIA
      significantly overestimates vancomycin serum concentrations compared with EMIT in
      patients with ESRD undergoing high-efficiency hemodialysis. The overestimation by
      FPIA may result in significantly different vancomycin dosing recommendations,
      leading to underdosing and the potential for therapeutic failures. Due to the
      unpredictability of the overestimation by FPIA, we were unable to formulate
      vancomycin dosing guidelines for institutions that use FPIA. Therefore, we
      recommend that the EMIT vancomycin assay be used in patients with ESRD to ensure
      appropriate dosing.

PMID- 8546141
TI  - Spinal epidural abscess in hemodialysis patients: report of three cases and
      review of the literature.
AB  - Spinal epidural abscess (SEA) is a rare infection that can evolve to severe
      permanent neurologic deficit or death if the diagnosis is delayed. We report
      three cases of SEA in hemodialysis patients and summarize nine previously
      reported cases occurring in hemodialysis patients, with detailed comparisons to
      series of SEA from the general medical literature. Among these 12 patients,
      hemodialysis catheters and arteriovenous grafts were the major source of
      infection, in contrast to the usual skin source. Staphylococcus aureus was
      implicated in all cases, but in one patient Bacteroides fragilis also was
      isolated from both the resected arteriovenous fistula and the SEA, and
      Escherichia coli was isolated from the arteriovenous fistula. The classic
      syndrome of SEA includes fever, backache, and local spinal tenderness, followed
      by progressive radicular and cord compression signs and symptoms. In this series,
      back pain and radicular pain were common at presentation, but only a minority had
      fever, back tenderness, weakness, or leukocytosis. Cerebrospinal fluid was
      typically abnormal but culture negative, whereas blood and epidural abscess
      cultures were frequently positive. Plain x-ray films, bone scans, and plain
      computed tomography scans had low diagnostic yield, and magnetic resonance
      imaging with gadolinium had a sensitivity of 80%. Only myelography or computed
      tomography-myelography gave consistently correct diagnoses. The clinical outcome
      was poor, with one patient deceased and seven with severe weakness or paralysis.
      Early intervention provided a higher likelihood of good outcome, whereas late
      intervention and preoperative neurologic deficits portended a poor functional
      result. Because of the high incidence of bacteremia in hemodialysis patients, we
      recommend that symptoms of fever, backache, and spinal tenderness be promptly
      evaluated for SEA before signs or symptoms of cord compression develop. Early
      recognition and treatment with antibiotics and decompressive laminectomy is
      generally associated with a better outcome.

PMID- 8546142
TI  - Low-density lipoprotein particle size distribution in end-stage renal disease
      treated with hemodialysis or peritoneal dialysis.
AB  - Dyslipidemia accompanies end-stage renal disease (ESRD) and contributes to the
      high incidence of cardiovascular disease in patients on chronic dialysis
      treatment. The lipid abnormalities of elevated triglyceride level and reduced
      high-density lipoprotein cholesterol level that occur in ESRD are associated in
      the normal population with an altered distribution of low-density lipoprotein
      (LDL) particle size, a pattern associated with increased risk of coronary heart
      disease. To assess the effect of ESRD on LDL particle size distribution, we
      examined plasma lipid levels and LDL particle size in 43 subjects on chronic
      hemodialysis, 23 subjects on continuous ambulatory peritoneal dialysis, and 30
      control subjects with normal renal function. Of subjects on continuous ambulatory
      peritoneal dialysis, 48% had small LDL particle size compared with 23% of
      subjects on hemodialysis and 7% of control subjects. Subjects on both forms of
      dialysis also had higher triglyceride levels and lower high-density lipoprotein
      cholesterol levels that correlated with LDL particle size. We conclude that
      altered LDL particle size forms an important component of the metabolic
      abnormalities that contribute to the increased cardiovascular risk found in ESRD.

PMID- 8546143
TI  - Enhancement of peritoneal dialysis: the PD Plus concept.
AB  - The need for a peritoneal dialysis modality capable of providing higher
      clearances of small solutes at a competitive cost with continuous ambulatory
      peritoneal dialysis (CAPD) has been identified. A new modality of therapy (PD
      Plus; Fresenius USA, Walnut Creek, CA), which is based on the principles of
      optimal dwell time and large exchange volumes while the patient is supine, is
      described. This technique combines automated cycles with a manual diurnal
      exchange. Seven patients were studied during CAPD and while on PD Plus.
      Peritoneal Kt/Vurea increased from 0.22 +/- 0.04 to 0.29 +/- 0.07 (P < 0.002),
      creatinine clearance from 37.69 +/- 2.45 to 51.14 +/- 8.34 L/wk/1.73 m2 (P <
      0.005), and normalized protein catabolic rate from 0.74 +/- 0.14 to 0.80 +/- 0.15
      g/kg/d during CAPD and PD Plus, respectively, with a mean increase in dialysis
      solution volume of only 2.76 L. A comparative cost-efficiency analysis
      demonstrated a highly significant increase in dialysis dose (delta Kt/Vurea 57%)
      for a small increase in cost (6%) between CAPD and PD Plus. The data suggest that
      a significant increase in dialysis dose is possible with a minimal increase in
      the cost of therapy.

PMID- 8546144
TI  - Four-year experience with swan neck presternal peritoneal dialysis catheter.
AB  - The swan neck presternal catheter is composed of two flexible (silicon rubber)
      tubes joined by a titanium connector at the time of implantation. The exit site
      is located in the presternal or parasternal area. The catheter located on the
      chest was designed to reduce the incidence of exit site infections compared with
      peritoneal dialysis catheters with abdominal exit sites. From August 1991 to May
      1995, 24 swan neck presternal catheters have been implanted in 24 patients for
      the following reasons: obesity nine patients, ostomies three patients, a
      suprapubic catheter one patient, previous problems with abdominal catheters two
      patients, desire to use a bathtub five patients, need to use a whirlpool one
      patient, need to wear sweatpants with an elastic waistband one patient, and body
      image two patients. In the same period, 47 abdominal swan neck catheters were
      implanted in 44 patients who preferred catheters with the exit on the abdomen.
      Presternal catheters tended to perform better regarding exit and tunnel
      infections, even though they were implanted in several patients in whom regular
      catheters with the exit on the abdomen would be difficult or impossible to
      implant. Two-year survival probability of presternal catheters was 0.88 +/- 0.14
      (+/- SE). Recurrent/refractory peritonitis was the only reason of catheter
      failure. The differences in results between presternal and abdominal catheters
      were statistically insignificant; only the use of antibiotics to treat exit site
      infection was significantly higher with abdominal catheters. Patient acceptance
      of the exit position was good; at least seven patients preferred presternal
      catheter for psychological or body image reasons. We conclude that the swan neck
      presternal catheters provide excellent results comparable to those achieved with
      swan neck abdominal catheters. The catheter seems suitable for any patient
      commencing peritoneal dialysis and is particularly useful in extremely obese
      patients (body mass index > 40 kg/m2) and those with ostomies. The catheter exit
      location in the chest may be preferred by some patients, both men and women, for
      psychological or body image reasons. No specific contraindications to the
      presternal catheter implantation have been identified.

PMID- 8546145
TI  - Familial richner-Hanhart syndrome in Kuwait: twelve-year clinical reassessment by
      a multidisciplinary approach.

PMID- 8546146
TI  - Intelligence and achievement in children with extra X aneuploidy: a longitudinal
      perspective.
AB  - Forty-seven children (35 male, 12 female) identified as having a supernumerary X
      chromosome by neonatal screening were studied psychologically from childhood to
      late adolescence. This paper compares their findings relative to sibling controls
      on tests of intelligence and achievement collected over a 14-year period.
      Children with a supernumerary X chromosome were found to score consistently below
      controls on Verbal IQ and subtests comprising the Verbal Comprehension factor but
      they did not differ on Performance IQ, which was in the normal range. At all
      ages, they showed poorer reading and arithmetic achievement; relative risk for
      reading and arithmetic impairment was 2.6 and 2.6 in males and 1.1 and 1.7 in
      females. Males with an extra X chromosome were more likely to receive special
      education than females, who more often failed a grade. Academic achievement was
      not affected in aneuploid children with higher levels of intelligence. Overall,
      these results suggest milder impairment than previously reported, particularly
      among trisomy X females.

PMID- 8546147
TI  - Two sisters with clinical diagnosis of Wiskott-Aldrich syndrome: is the condition
      in the family autosomal recessive?
AB  - We report two sisters in a family representing manifestations of Wiskott-Aldrich
      syndrome (WAS), an X-linked immunodeficiency disorder. An elder sister had
      suffered from recurrent infections, small thrombocytopenic petechiae, purpura,
      and eczema for 7 years. The younger sister had the same manifestations as the
      elder sister's for a 2-year period, and died of intracranial bleeding at age 2
      years. All the laboratory data of the two patients were compatible with WAS,
      although they were females. Sialophorin analysis with the selective radioactive
      labeling method of this protein revealed that in the elder sister a 115-KD band
      that should be specific for sialophorin was reduced in quantity, and instead an
      additional 135-KD fragment was present as a main band. Polymerase chain reaction
      (PCR) analysis of the sialophorin gene and single-strand conformation
      polymorphism (SSCP) analysis of the PCR product demonstrated that there were no
      detectable size-change nor electrophoretic mobility change in the DNA from both
      patients. The results indicated that their sialophorin gene structure might be
      normal. Studies on the mother-daughter transmission of X chromosome using a
      pERT84-MaeIII polymorphic marker mapped at Xp21 and HPRT gene polymorphism at
      Xq26 suggested that each sister had inherited a different X chromosome from the
      mother. Two explanations are plausible for the occurrence of the WAS in our
      patients: the WAS in the patients is attributable to an autosomal gene mutation
      which may regulate the sialophorin gene expression through the WAS gene, or,
      alternatively, the condition in this family is an autosomal recessive disorder
      separated etiologically from the X-linked WAS.

PMID- 8546148
TI  - Bipolar disorder: evidence for a major locus.
AB  - Complex segregation analyses were conducted on families of bipolar I and bipolar
      II probands to delineate the mode of inheritance. The probands were ascertained
      from consecutive referrals to the Mood Disorder Service, University Hospital,
      University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic
      Criteria. Data were available on over 1,500 first-degree relatives of the 186
      Caucasian probands. The purpose of the analyses was to determine if, after
      correcting for age and birth cohort, there was evidence for a single major locus.
      Five models were fit to the data using the statistical package SAGE: i) dominant,
      ii) recessive, iii) arbitrary mendelian inheritance, iv) environmental, and v) no
      major effects. A single dominant, mendelian major locus was the best fitting of
      these models for the sample of bipolar I and II probands when only bipolar
      relatives were defined as affected (polygenic inheritance could not be tested).
      Adding recurrent major depression to the diagnosis "affected" for relatives
      reduced the evidence for a major locus effect. Our findings support the
      undertaking of linkage studies and are consistent with the analyses of the
      National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et
      al. (Arch Gen Psychiatry 44: 441-447, 1987) and Blangero and Elston (Genet
      Epidemiol 6:221-227, 1989).

PMID- 8546149
TI  - Schizophrenia and the androgen receptor gene: report of a sibship showing co
      segregation with Reifenstein syndrome but no evidence for linkage in 23 multiply
      affected families.
AB  - Crow et al. [1993: Am J Med Genet (Neuropsychiatr Genet) 48:159-160] have
      reported excess sharing of alleles by male sibling pairs with schizophrenia, at a
      triplet repeat marker within the androgen receptor gene, indicating that
      mutations at or near this gene may be a risk factor for males. In this report, we
      describe a pair of male siblings concordant for both schizophrenia and
      Reifenstein syndrome, which is caused by a mutation in this gene. This provides
      support for the hypothesis that the androgen receptor may contribute to liability
      to develop schizophrenia. Because of this, we have examined a collection of 23
      pedigrees multiply affected by schizophrenia for linkage to the androgen
      receptor. We have found no evidence for linkage by both the LOD score and
      affected sibling-pair methods, under a range of genetic models with a broad and
      narrow definition of phenotype, and when families with male-to-male transmission
      are excluded. However, because of the small number of informative male-male pairs
      in our sample, we cannot confirm or refute the excess allele sharing for males
      reported by Crow.

PMID- 8546150
TI  - SCA2 is not a major locus for ADCA type I in French families.
AB  - Autosomal dominant cerebellar ataxias (ADCA) of type I, a group of clinically
      heterogeneous neurodegenerative disorders, are known to be genetically
      heterogeneous since a second locus for ADCA type I (SCA2) has been identified on
      the long arm of chromosome 12. Linkage analysis was performed in 7 French ADCA
      type I families in order to estimate its frequency. We analysed 121 individuals,
      39 of whom were affected. In 6 families, the SCA2 candidate interval, spanning
      12.8 cM, was excluded by bi- and multipoint analysis. In one family (SAL-315),
      however, the maximal positive lod score reached 2.03 at the D12S79 locus. A
      posterior probability of 94% in favor of linkage to SCA2 was calculated by
      homogeneity analysis. The clinical profile of this family was similar to that of
      previously described SCA1 and non-SCA1 families, except that dementia was
      observed in 2 out of 6 patients. This may be a clinical idiosyncrasy in this
      family and was insufficient for a genotype-phenotype correlation.

PMID- 8546151
TI  - Linkage analysis between manic-depressive illness and markers on the long arm of
      chromosome 11.
AB  - The long arm of chromosome 11 is one of the most interesting regions in the
      search for major genes involved in the etiology of manic-depressive illness.
      Several candidate genes have been identified, including the gene encoding the
      dopamine D2 receptor, the M1 muscarinic receptor, and porfobillinogen deaminase.
      Furthermore, different families with co-segregation of psychiatric illness and
      structural chromosome abnormalities involving regions 11q21, 11q22.3, and 11q25
      have been reported. Using narrow as well as broad phenotypic models, conservative
      genetic parameters, models with dominant or recessive modes of inheritance, and
      various methods to reduce misclassification, the present study did not find
      evidence for a major gene causing manic-depressive illness on the long arm of
      chromosome 11. In the broader phenotypic models multi-point analyses excluded at
      least 11q14 to 11q23.3, approximately 60 cM, even in one large family. Assuming
      homogeneity close linkage to DRD2 was excluded for all dominant models, and also
      in the affecteds-only analyses in the large family alone.

PMID- 8546152
TI  - Systematic screening for mutations in the promoter and the coding region of the 5
      HT1A gene.
AB  - In the present study we sought to identify genetic variation in the 5-HT1A
      receptor gene which through alteration of protein function or level of expression
      might contribute to the genetic predisposition to neuropsychiatric diseases.
      Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46
      bipolar affective, and 43 patients with Tourette's syndrome, as well as 25
      healthy controls) were investigated by single-strand conformation analysis.
      Overlapping PCR (polymerase chain reaction) fragments covered the whole coding
      sequence as well as the 5' untranslated region of the 5-HT1A gene. The region
      upstream to the coding sequence we investigated contains a functional promoter.
      We found two rare nucleotide sequence variants. Both mutations are located in the
      coding region of the gene: a coding mutation (A-->G) in nucleotide position 82
      which leads to an amino acid exchange (Ile-->Val) in position 28 of the receptor
      protein and a silent mutation (C-->T) in nucleotide position 549. The occurrence
      of the Ile-28-Val substitution was studied in an extended sample of patients (n =
      352) and controls (n = 210) but was found in similar frequencies in all groups.
      Thus, this mutation is unlikely to play a significant role in the genetic
      predisposition to the diseases investigated. In conclusion, our study does not
      provide evidence that the 5-HT1A gene plays either a major or a minor role in the
      genetic predisposition to schizophrenia, bipolar affective disorder, or
      Tourette's syndrome.

PMID- 8546153
TI  - Relationship of genetically transmitted alpha EEG traits to anxiety disorders and
      alcoholism.
AB  - We tested the hypothesis that a heritable EEG trait, the low voltage alpha (LV),
      is associated with psychiatric disorders. Modest to moderate evidence for genetic
      linkage of both panic disorder and the low voltage alpha trait to the same region
      of chromosome 20q has recently been reported, raising the issue of whether there
      is a phenotypic correlation between these traits. A total of 124 subjects
      including 50 unrelated index subjects and 74 relatives were studied. Alpha EEG
      power was measured and EEG phenotypes were impressionistically classified.
      Subjects were psychiatrically interviewed using the SADS-L and blind-rated by RDC
      criteria. Alcoholics were four times more likely to be LV (including so-called
      borderline low voltage alpha) than were nonalcoholic, nonanxious subjects.
      Alcoholics with anxiety disorder are 10 times more likely to be LV. However,
      alcoholics without anxiety disorder were similar to nonalcoholics in alpha power.
      An anxiety disorder (panic disorder, phobia, or generalized anxiety) was found in
      14/17 LV subjects as compared to 34/101 of the rest of the sample (P < 0.01).
      Support for these observations was found in the unrelated index subjects in whom
      no traits would be shared by familial clustering. Lower alpha power in anxiety
      disorders was not state-dependent, as indicated by the Spielberger Anxiety Scale.
      Familial covariance of alpha power was 0.25 (P < 0.01). These findings indicate
      there may be a shared factor underlying the transmissible low voltage alpha EEG
      variant and vulnerability to anxiety disorders with associated alcoholism. This
      factor is apparently not rare, because LV was found in approximately 10% of
      unrelated index subjects and 5% of subjects free of alcoholism and anxiety
      disorders.

PMID- 8546154
TI  - Monoamine oxidases and alcoholism. I. Studies in unrelated alcoholics and normal
      controls.
AB  - Low platelet MAO activity has been associated with alcoholism. In order to
      evaluate the role of MAO genes in susceptibility to alcoholism, we have taken a
      biochemical and molecular genetic approach. The sample consisted of 133 alcoholic
      probands who were classified by subtypes of alcoholism and 92 normal controls.
      For those subjects typed for platelet MAO activity, alcoholics (N = 74) were
      found not to differ from the non-alcoholics controls (N = 34). Neither was there
      a significant difference between type I and type II alcoholics or between either
      subtype and normal controls. However, we do find significant differences between
      male and female alcoholics, but not between male and female controls. The allele
      frequency distribution for the MAO-A and MAO-B dinucleotide repeats is different
      between the alcoholic sample (N = 133) and the normal control sample (N = 92). In
      a two-way analysis of variance of MAO-B activity as a function of the allelic
      variation of each marker locus and diagnosis, there is no evidence for mean
      differences in activity levels for the different alleles. Our findings do not
      rule out a role for the MAO-B gene in controlling the enzyme activity because the
      dinucleotide repeats are located in introns.

PMID- 8546155
TI  - Monoamine oxidases and alcoholism. II. Studies in alcoholic families.
AB  - Thirty-five alcoholic families have been studied to investigate the relationship
      between DNA markers at the monoamine oxidase (MAO) loci and 1) platelet activity
      levels and 2) alcoholism. A quantitative linkage analysis failed to reveal any
      evidence that the variation in activity levels cosegregates with the DNA markers.
      A sib-pair analysis did not reveal a significant excess of MAO haplotype sharing
      among alcoholic sibs, although the deviation from random sharing was in the
      direction consistent with an X-linked component. A reanalysis of platelet MAO
      activity levels in a subset of these families revealed that the lower levels
      previously found in alcoholics is more likely due to the differences between
      males and females. Only among males and only when a "broad" definition of
      alcoholism is used (and MAO activity levels are transformed to normality) does it
      appear that alcoholics have depressed activities compared to nonalcoholics.
      Finally, when the confounding due to gender difference is removed, no differences
      between type I and type II alcoholics are found in these families.

PMID- 8546156
TI  - Systematic search for major genes in schizophrenia: methodological issues and
      results from chromosome 12.
AB  - We describe a method of systematically searching for major genes in disorders of
      unknown mode of inheritance, using linkage analysis. Our method is designed to
      minimize the probability of missing linkage due to inadequate exploration of
      data. We illustrate this method with the results of a search for a locus for
      schizophrenia on chromosome 12 using 22 highly polymorphic markers in 23 high
      density pedigrees. The markers span approximately 85-90% of the chromosome and
      are on average 9.35 cM apart. We have analysed the data using the most plausible
      current genetic models and allowing for the presence of genetic heterogeneity.
      None of the markers was supportive of linkage and the distribution of the
      heterogeneity statistics was in accordance with the null hypothesis.

PMID- 8546157
TI  - Lack of association between manic-depressive illness and a highly polymorphic
      marker from GABRA3 gene.
AB  - We have carried out an association study between a dinucleotide repeat
      polymorphism in GABRA3 gene and manic-depressive illness in a Spanish population.
      This may be an important candidate gene for bipolar affective disorders since it
      is located in the Xq28 region, previously implicated in linkage studies. In
      addition, severe GABergic alterations have been reported in patients. We have not
      found significant differences between controls and patients in allele frequencies
      or genotypes.

PMID- 8546158
TI  - Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.
AB  - In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported
      by Pulver et al. [1994: Am J Med Genet 54:36-43], we have analyzed 4
      microsatellite markers which span this chromosomal region, including the IL2RB
      locus, for linkage with schizophrenia in 30 families from Israel and Germany.
      Linkage analysis by pairwise lod score analysis as well as by multipoint analysis
      did not provide evidence for a single major gene locus. However, a lod score of
      Zmax = 0.612 was obtained for a dominant model of inheritance with the marker
      D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a
      nonparametric method, sib pair analysis, a P value of 0.068 corresponding to a
      lod score of 0.48 was obtained for this marker. This finding, together with those
      of Pulver et al. [1994: Am J Med Genet 54:36-43] and Coon et al. [1994: Am J Med
      Genet 54:72-79], is suggestive of a genetic factor in this region, predisposing
      for schizophrenia in a subset of families. Further studies using nonparametric
      methods should be conducted in order to clarify this point.

PMID- 8546159
TI  - Increased chromosomal breakage in Tourette syndrome predicts the possibility of
      variable multiple gene involvement in spectrum phenotypes: preliminary findings
      and hypothesis.
AB  - Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette
      syndrome (TS) as compared with 10 non-TS control individuals with respect to
      untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in
      each category). A hypothesis is proposed that a major TS gene is probably
      connected to genetic instability, and associated chromosomal marker sites may be
      indicative of the localization of secondary genes whose altered expression could
      be responsible for associated comorbid conditions. This concept implies that
      genes influencing higher brain functions may be situated at or near highly
      recombigenic areas allowing enhanced amplification, duplication and recombination
      following chromosomal strand breakage. Further studies on a larger sample size
      are required to confirm the findings relating to chromosomal breakage and to
      analyze the possible implications for a paradigmatic shift in linkage strategy
      for complex disorders by focusing on areas at or near unstable chromosomal marker
      sites.

PMID- 8546160
TI  - Association study of schizophrenia and the IL-2 receptor beta chain gene.
AB  - A case-control association study was conducted in Caucasian patients with
      schizophrenia (DSM-III-R, n = 42) and unaffected controls (n = 47) matched for
      ethnicity and area of residence. Serum interleukin-2 receptor (IL-2R)
      concentrations, as well as a dinucleotide repeat polymorphism in the IL-2R beta
      chain gene, were examined in both groups. No significant differences in IL-2R
      concentrations or in the distribution of the polymorphism were noted. This study
      does not support an association between schizophrenia and the IL-2R beta gene
      locus, contrary to the suggestive evidence from linkage analysis in multicase
      families.

PMID- 8546161
TI  - Association study between the dopamine D4 receptor gene and schizophrenia.
AB  - The dopamine D4 receptor is of major interest in schizophrenia research due to
      its high affinity for the atypical neuroleptic clozapine and a high degree of
      variability in the receptor gene (DRD4). Although several genetic linkage
      analyses performed on schizophrenia multiplex families from different regions of
      the world have either excluded or failed to prove that DRD4 is a major genetic
      factor for the development of schizophrenia, analyses for moderate predisposing
      effects are still of significant interest. We performed a study examining
      differences in allele frequencies of 4 different DRD4 polymorphisms in
      schizophrenia patients and age, sex, and ethnic origin matched controls. None of
      these 4 polymorphisms showed evidence for genetic association with schizophrenia,
      although a trend towards excess of the allele with 7 repeats in the (48)n bp exon
      III polymorphism was observed. Complexities in the DRD4 genetic investigation and
      further analytic approaches are discussed.

PMID- 8546162
TI  - Apolipoprotein E in the genetics and epidemiology of Alzheimer's disease.
AB  - The role of apolipoprotein E (ApoE) alleles and isoforms in the etiology and
      pathogenesis of Alzheimer's disease is discussed. The possibility that ApoE
      itself is not involved in the disease pathogenesis but is merely in genetic
      disequilibrium with the real locus is discussed and dismissed. The data showing
      that the epsilon 4 allele is associated with an increased risk of developing the
      disease and with an earlier onset age are reviewed. The data showing that, at
      least in some circumstances, the epsilon 2 allele is associated with a decrease
      in the risk of developing the disease, and with a later onset age are also
      reviewed. Data from the genetic analysis of other disorders are reviewed and
      presented, and it is suggested that the genetic data support the notion that the
      role of ApoE in the etiology of the disease directly relates to beta-amyloid
      deposition and plaque formation. This suggestion is in concordance with the most
      likely mechanism for the role of beta-amyloid precursor protein gene mutations as
      other risk factors for the disease.

PMID- 8546163
TI  - No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia.
AB  - DeLisi et al. (1994b) have examined the X and Y chromosomes for linkage to
      schizophrenia in 126 small families and report a small positive LOD score for the
      marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have
      examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male
      to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped
      using the PCR and LOD scores calculated using five models of inheritance,
      including classical dominant recessive and intermediate models. LOD scores were
      substantially negative for all models examined and analysis for linkage
      heterogeneity using the LOD2 method showed no significance. Analysis by the
      nonparametric affected sib-pair method likewise indicated no linkage. We conclude
      that DXS7 is not a major locus for schizophrenia in our collection of pedigrees.

PMID- 8546164
TI  - Potential linkage disequilibrium between schizophrenia and locus D22S278 on the
      long arm of chromosome 22.
AB  - Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis.
      In order to replicate these results, we performed the transmission test for
      linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their
      226 parents. Evidence for potential linkage disequilibrium was obtained between
      schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P =
      0.02). The results of our study suggest a detectable oligogenic gene in a
      multigene system for schizophrenia closely linked to D22S278 on the long arm of
      chromosome 22. If confirmed by others, this finding could lead to the
      identification of a schizophrenia susceptibility gene.

PMID- 8546166
TI  - Efficient removal of albumin-bound furancarboxylic acid by protein-leaking
      hemodialysis.
AB  - Furancarboxylic acid (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, CMPF),
      an inhibitor of erythropoiesis, cannot be removed by conventional hemodialysis
      due to its strong albumin binding, resulting in its accumulation in uremic serum.
      We used protein-leaking hemodialysis with BK-F dialyzers in 8 uremic patients for
      4 months to determine its effect on the serum levels of CMPF. Pre-hemodialysis
      serum levels of CMPF significantly decreased to about 50% after 4 months by
      protein-leaking hemodialysis, while those of BUN and serum creatinine did not
      change significantly. Pre-hemodialysis hematocrit and hemoglobin levels
      significantly increased by protein-leaking hemodialysis. These results indicate
      that protein-leaking hemodialysis reduces serum levels of albumin-bound CMPF and
      improves anemia.

PMID- 8546165
TI  - Structure of dialysis membranes and long-term clinical outcome.
AB  - The present comparative evaluation aims at establishing whether the basic
      structure of dialysis membrane is able to predict long-term clinical outcome.
      From a population of 1,256 patients on renal dialysis treatment, treated by the
      Institute of Nephrology and Dialysis of the St. Orsola University Hospital of
      Bologna from 1963 to 1993, 122 patients were retrospectively selected for the
      present study. Patients were divided into two different groups according to the
      kind of dialysis membrane used--cellulose-based (64 patients) and synthetic-based
      (58 patients) membranes. The parameters considered were: intradialytic biology,
      long-term biocompatibility, survival and morbidity, and cost/benefit. The results
      obtained demonstrate that cellulosic membranes can be said to cause a greater
      acute intradialytic biological response than synthetics, though not to a
      significant degree. There are, however, no significant differences in the
      biological changes from group to group. Nonsignificant differences were noted in
      long-term survival general morbidity. In terms of sheer cost, synthetic membrane
      treatment is anything up to 200% dearer than cellulosic.

PMID- 8546167
TI  - Serum CA-125 level in end-stage renal disease patients maintained on chronic
      peritoneal dialysis or hemodialysis: the effect of continuous presence of
      peritoneal fluid, peritonitis, and peritoneal catheter implantation.
AB  - Serum Ca-125, an ovarian tumor marker, is used to screen and follow up patients
      with overian cancer. Normal values (< 35 U/ml) have been reported in patients
      with end-stage renal disease and patients maintained on chronic hemodialysis
      (HD). Non-malignant ascites has been associated with high serum levels of CA-125,
      suggesting that the presence of fluid in the peritoneal cavity may stimulate its
      release. We studied 38 HD and 43 chronic ambulatory peritoneal dialysis (CAPD)
      patients with regard to serum CA-125 levels. In the HD patients, the mean +/- SE
      serum CA-125 level was 10.1 +/- 1.7 U/ml (range < 5-39) with 8% of the patients
      having serum levels of > 35 U/ml. In the CAPD patients, the mean serum CA-125
      level in all samples collected (n = 68) was 17.7 +/- 2.7 U/ml (range < 5-101, p <
      0.01 vs. HD) with 16% of the sera showing levels of > 35 U/ml. The high serum CA
      125 levels in the CAPD patients were from sera obtained within 2 months of
      diagnosis of peritonitis, peritoneal dialysis (PD) catheter implantation, or
      intra-abdominal surgery. When serum samples from this 2-month period were
      excluded, the mean serum CA-125 level was 8.9 +/- 1.5 U/ml (p = NS vs. HD) and
      only 1 patient had an abnormal level. Peritoneal dialysate CA-125 levels during
      an episode of peritonitis were significantly higher than at the baseline (69.1 +/
      14.2 vs. 21 +/- 2.5, p = 0.004) and both were significantly higher than the
      serum levels (p < 0.0001). Serum CA-125 levels were also the same in both sexes
      and races. In conclusion, it was found that while the serum CA-125 level is
      within normal limits in the majority of HD and stable CAPD patients, it is not
      uncommon that it is elevated in CAPD patients within 2 months of peritonitis, PD
      catheter placement, or intra-abdominal surgery, particularly when peritoneal
      exchanges are temporarily on hold in the latter two. The serum CA-125 level
      should be interpreted with caution in the CAPD patients as it may be a non
      specific marker of peritoneal irritation. It was also found that there was a
      significant removal of CA-125 by the peritoneal fluid which markedly increased
      during episodes of peritonitis.

PMID- 8546168
TI  - Acute renal failure in patients following bone marrow transplantation:
      prevalence, risk factors and outcome.
AB  - To assess the prevalence, risk factors, clinical causes and outcome of acute
      renal failure (ARF) following bone marrow transplantation (BMT), a retrospective
      analysis of 275 patients was undertaken. ARF was diagnosed in 72 patients (26%)
      and occurred in 81.9% within the first month. The three main clinical causes were
      multifactorial (36%), nephrotoxic (29%), and veno-occlusive disease of the liver
      (VOD) 15%. The prevalence was higher in allogeneic BMT (36%) than in autologous
      BMT (6.5%). Risk factors related to the development of ARF wee preexisting VOD
      and age older than 25 years. Logistic regression in allogeneic BMT confirmed this
      association (VOD, odds ratio 3.8; age offer than 25, odds ratio 1.9). Underlying
      disease, graft-versus-host disease, sepsis, conditioning therapy, and sex were
      not associated with ARF. Seventeen cases of ARF required hemodialysis (24%)
      mainly in association with VOD (70.5%). The overall morality from ARF was 45.8%,
      the dialyzed group having the highest mortality (88%). Survival in the ARF group
      was continuously worse up to 3 months and the actuarial survival at 10 years was
      29.7 versus 53.2%. We conclude that ARF is a common complication mainly in
      allogeneic BMT and carries a grave prognosis. VOD and age were risk factors for
      ARF.

PMID- 8546169
TI  - Correction of glucose concentration interference on Jaffe kinetic creatinine
      assay in peritoneal dialysis.
AB  - Overestimation of creatinine measurement using the Jaffe kinetic method in
      peritoneal dialysis solutions, due to glucose interference, has been quantified
      and corrected through the elaboration of linear formulas obtained from 110
      recovery and 301 biological tests. The added pure powdered creatinine and
      enzymatic method were considered as references after proven accuracy. Considering
      creatinine as well as glucose concentration interference, we obtained correction
      formulas from multiple regression application. All the computed formulas gave
      satisfactory corrections but different accuracy levels. The best model in
      biological samples was: Corrected CR = K1JaffeCr + K2Glucose (all values in
      mg/dl) where K1 = 0.973 and K2 = -0.00035 (Rsq = 0.987, F ratio = 10,945, p =
      0.00001). Applying formulas to biological samples there was a drop in accuracy,
      possibly explained by the presence of numerous unidentified substances in
      peritoneal dialysis biological samples that can amplify scatter. Every laboratory
      can reduce the error of the Jaffe kinetic assay by calculating their own
      correction formula in relation to the method and instrument used, because Jaffe
      kinetic assay gives different results with different kinetic windows. So,
      especially when applied to peritoneal dialysis fluid measurements, if a
      creatinine assay reference method is not available, the correction formula can be
      applied directly as given. Otherwise the method we have described can be followed
      with a well-structured creatinine recovery fest to identify and quantify assay
      interferences.

PMID- 8546170
TI  - Risk factors for progression of diabetic nephropathy.
AB  - Fifty-four patients with noninsulin-dependent diabetes mellitus, who had
      established nephropathy, were examined to evaluate the risk factors for the
      progression of diabetic nephropathy. Time-averaged values of blood pressure,
      serum total cholesterol and fasting plasma glucose concentrations, and the degree
      of proteinuria during their follow-up period (4.2 +/- 0.5 years) were calculated.
      The correlation between these values and the slope of the regression line for the
      reciprocal of serum creatinine concentration over time, as an index of the speed
      of the progression of nephropathy, was examined. Age (61 +/- 1 years), mean
      arterial pressure (109 +/- 1 mm Hg), and the degree of the proteinureia (2.1 +/-
      0.1 in dipstick test) were correlated with the slope. Effects of
      hypercholesterolemia and smoking on the slope were also examined. Mean arterial
      pressure was correlated with the slope significantly in patients without
      hypercholesterolemia (p < 0.05) and there was a tendency between these two in
      smokers (p < 0.06), while was no correlation found in patients with
      hypercholesterolemia or in nonsmokers. In addition, the relation between the
      slope and mean arterial pressure was relatively stronger in smokers without
      hypercholesterolemia than in nonsmokers with hypercholesterolemia. Our data
      suggest that blood pressure control as well as smoking avoidance may be important
      in preventing the progression of noninsulin-dependent diabetic nephropathy.

PMID- 8546171
TI  - Coadministration of ketoconazole to cyclosporin-treated kidney transplant
      recipients: a prospective randomized study.
AB  - In this work, 100 living related donor kidney transplant recipients under
      cyclosporin (CsA) therapy were randomly distributed to two groups. Group 1 were
      administered ketoconazole, with group 2 serving as the control. Ketoconazole was
      given orally, 100 mg/day, while the dose of CsA was adjusted for a CsA whole
      blood trough level of 100-150 ng/ml. Patients and controls were assessed
      regularly in an outpatient clinic for 12 months and compared statistically for
      CsA dose, graft and liver functions, cholesterol, blood sugar, CsA
      nephrotoxicity, acute rejection episodes, chronic rejection and fungal skin
      infections. Statistical analysis showed a significant reduction in the CsA dose
      in the ketoconazole-treated group (73-76%), along with significantly lower
      alanine aminotransferase, aspartate aminotransferase, bilirubin, and serum
      creatinine values. CsA chronic nephrotoxicity and chronic rejections were also
      significantly lower in the ketoconazole-treated group, as was fungal skin
      infection (6.6 vs 63.2%). From this study, we conclude that addition of a low
      dose of ketoconazole to CsA-treated kidney transplant recipients not only saves
      costs, but may also have a favorable effect on graft function, chronic CsA
      nephrotoxicity, chronic rejection and fungal skin infection.

PMID- 8546172
TI  - Indium-111-labeled granulocyte head accumulation in patients with Wegener's
      granulomatosis.
AB  - Among the symptoms of systemic vasculitis, purulent rhinorrhea with painful
      sinusitis is thought to be relatively specific to Wegener's granulomatosis (WG).
      Sixteen patients with rapidly progressive glomerulonephritis (GN), arteritis and
      extensive crescents in renal biopsy were studied by head indium-111 (111In)
      granulocyte scanning. They included 8 WG, 5 microscopic polyarteritis, 2
      necrotizing and crescentic GN and 1 classic polyarteritis nodosa. Autologous
      granulocytes labeled with 12.3 MBq of 111In-oxine were administered
      intravenously. Scintigraphic studies were performed at 4 and 24 h post-injection.
      Compared to the non-WG cases, considered as a whole, significant accumulation of
      tracer in sinuses was observed in WG patients (Fisher's p = 0.02). Substantial
      scintigraphic amelioration was obtained in a WG case treated with
      methylprednisolone pulses and, in another WG case, after high doses of
      intravenous gamma-globulins. The complete disappearance of facial uptake was
      obtained after 2 months of intensive therapy (i.e., steroid, cyclophosphamide and
      plasma exchange) in another WG patient. 111In-oxine granulocyte imaging may be
      useful in clinical practice as an additional marker of disease activity and a
      tool of identification of upper respiratory tract involvement.

PMID- 8546173
TI  - Serum parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D3 in
      patients on maintenance haemodialysis.
AB  - Secondary hyperparathyroidism in patients with end-stage renal disease is
      characterised by elevated circulating levels of parathyroid hormone, due to
      inadequate synthesis of calcitriol, the active metabolite of vitamin D. Recent
      studies suggest that administration of calcitriol may directly suppress
      parathyroid (PTH) secretion independent of changes in serum calcium. We have
      studied the effect of intravenous calcitriol administration on the PTH level in
      14 patients on maintenance haemodialysis with serum PTH levels above 2,000 pmol/l
      over a 16-week period. There was a significant reduction in the PTH level (65%)
      and a rise of serum calcium to the normal range. There was a significant
      reduction in serum PTH levels before the serum calcium concentrations increased,
      suggesting that calcitriol directly inhibits PTH release. In conclusion,
      intravenous treatment with calcitriol is of clinical importance, because it
      suppresses hypersecretion of PTH in uraemic patients, with minimal side effects.

PMID- 8546174
TI  - Quiz of the month.

PMID- 8546176
TI  - Infected arteriovenous hemodialysis graft presenting as left and right infective
      endocarditis.
AB  - Prosthetic grafts have become an acceptable alternative to the autogenous
      arteriovenous dialysis fistula. The major drawback in their use for the dialysis
      patient is infection. We present a case of infected polytetrafluoroethylene
      arteriovenous fistula (endarteritis) with signs of unilateral splinter
      hemorrhage, Janeway lesions in the affected limb and septic venous embolization
      to the lungs. The graft eventually ruptured requiring emergency surgery.
      Staphylococcus aureus is by far the most common implicated organism. An otherwise
      non-threatening infection at a fistula site can lead to more serious
      complications such as infective endocarditis.

PMID- 8546175
TI  - Potassium-wasting nephropathy in an outbreak of chronic organic mercurial
      intoxication.
AB  - An outbreak of organic mercurial intoxication in a peasant family from the Jordan
      West Bank is reported. Extrapyramidal symptoms, muscular wasting, oral
      ulcerations, and renal tubular dysfunction were the main manifestations.
      Hpyokalemia (1.9-2.7 mEq/l) due to urinary potassium wasting was present in all 4
      patients. Type II RTA was observed in 2 cases. Urinary ammonium excretion was
      increased over the range predicted by the given urinary pH in all the patients.
      Intrinsic tubular damage, nonreabsorbable anions of catabolic origin, increased
      prostaglandin synthesis inducing renin-angiotensin axis activation, and,
      consequently, inappropriate relatively high levels of aldosterone, are advanced
      as an explanation for potassium wasting.

PMID- 8546177
TI  - Calciphylaxis in a chronic hemodialysis patient with protein S deficiency.
AB  - Vascular calcifications are common in uremic patients whereas calciphylaxis is
      rare. We report the case of a 45-year-old woman on chronic hemodialysis since
      1977. She had a subtotal parathyroidectomy in 1985, aortic and mitral valve
      replacement in 1986, and has been treated since then with nicoumalone. In June
      1991, she presented with repeated, painful cutaneous necrosis suggesting
      panniculitis. A skin biopsy showed lobular panniculitis and evidence of
      calciphylaxis. There was an obvious biological hyperparathyroidism. Protein C
      functional level was in the normal range whereas protein S functional level was
      low, i.e. 42%. The patient underwent cervical surgery to remove two parathyroid
      glands, and daily hemodialysis sessions. Despite this treatment, cutaneous
      necrosis progressed with superinfection. A few weeks later, the patient died from
      a septic shock after a myocardic infarction. Necropsy was not performed.

PMID- 8546178
TI  - An unrecognized renal physiologist: Friedrich Wohler.
AB  - Wohler, in 1828, was the first chemist to synthesize urea. In 1824, towards the
      end of his medical studies, he had already published an important article on the
      renal excretion of some 41 substances administered orally or parenterally and on
      the links between their renal excretion and their metabolism: salts of potassium
      are excreted either reduced or oxidized, urine can be acidic when the blood is
      alkaline, the rate of water excretion is influenced by the rate of substances
      excreted in the same form as they are administered. He adumbrated the general
      concepts on the role of the kidney in the maintenance of the composition of the
      body. Had he continued in this direction, Wohler would have been recognized not
      only as a remarkable chemist but also as a great physiologist.

PMID- 8546179
TI  - Bilateral laparoscopic nephrectomy in a patient with renal transplant.

PMID- 8546180
TI  - Advanced glycation end products are associated with beta 2-microglobulin
      amyloidosis.

PMID- 8546181
TI  - Sulfa drug reaction.

PMID- 8546182
TI  - Alcoholic patients: keeping hope alive.

PMID- 8546183
TI  - Finding the 'I' in the 'we'.

PMID- 8546184
TI  - What every woman should know about menopause.

PMID- 8546185
TI  - Back to basics. Administering i.m. injections the right way.

PMID- 8546186
TI  - Chronic renal failure.

PMID- 8546187
TI  - Managing vascular leg ulcers. Part 1: Assessment.

PMID- 8546188
TI  - 'The daughter is a nurse'.

PMID- 8546189
TI  - Carbon monoxide poisoning.

PMID- 8546190
TI  - Books of the year.

PMID- 8546191
TI  - Grandmom's blessing.

PMID- 8546192
TI  - Treating neonates in pain.

PMID- 8546193
TI  - Pain during sickle-cell crises.

PMID- 8546194
TI  - Immigration: why is it still up for discussion?

PMID- 8546195
TI  - Luau in Vermont.

PMID- 8546196
TI  - 16th Annual meeting of the Society of Perinatal Obstetricians. Kamuela, Hawaii,
      February 4-10, 1996. Abstracts.

PMID- 8546198
TI  - Cytokine-mediated induction of endothelial adhesion molecule and
      histocompatibility leukocyte antigen expression by cytomegalovirus-activated T
      cells.
AB  - Cytomegalovirus (CMV) has been associated with allograft rejection and
      transplantation-associated arteriosclerosis. CMV infects endothelium, the
      interface between allograft tissue and the host immune system; however,
      mechanisms by which such interaction might exacerbate the rejection process
      remain unresolved. Here we test the hypothesis that host immune activity,
      triggered by CMV-infected graft endothelial cells (ECs), can result in the
      production of cytokines capable of enhancing the alloimmunogenicity of nearby
      uninfected endothelia. To model these phenomena in vitro, confluent monolayers of
      ECs derived from human umbilical vein or adult gonadal vein were incubated 5 days
      beneath trans-well culture inserts containing CMV-seropositive or CMV
      seronegative donor-derived CD3+ or CD4+ T cells alone or in combination with CMV
      infected or uninfected allogeneic ECs. The extent of T cell proliferation was
      determined by [3H]thymidine labeling of trans-well contents after transfer to
      microtiter plates. Endothelial responses to soluble factors elaborated by CMV
      activated T cells were determined by immunohistochemical staining and
      immunofluorescence flow cytometric analysis of underlying EC monolayers. Results
      of experiments with CMV-seropositive donor-derived CD4+ T cells demonstrated
      enhancement of ICAM-1 and histocompatibility leukocyte antigen class I, as well
      as induction of histocompatibility leukocyte antigen DR on ECs incubated beneath
      T cell/EC/CMV trans-well co-cultures. Total (CD3+) T cells co-cultured with
      EC/CMV induced VCAM-1 as well. Furthermore, [3H]thymidine incorporation by these
      T cells indicated a strong proliferative response. Endothelial responses to T
      cells alone or in combination with uninfected ECs were minimal, and T cells
      cultured under these conditions showed little proliferative activity. Similarly,
      little or no endothelial responses were apparent in monolayers beneath trans
      wells containing T cells isolated from CMV-seronegative individuals regardless of
      the CMV status of stimulator ECs. Finally, experiments employing blocking
      antibodies identified interferon-gamma and tumor necrosis factor-alpha as
      inducing agents in this co-culture system. These findings suggest that allograft
      endothelium harboring CMV has the potential to activate host T cells and that the
      consequent release of cytokines shows potential to raise surrounding endothelia
      to a fully activated, highly immunogenic state. Results of these studies thus
      provide insight into mechanisms that help elucidate the association between CMV
      and transplantation-associated arteriosclerosis and/or allograft rejection.

PMID- 8546199
TI  - Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic
      atherosclerotic lesions.
AB  - MMP-2, a secreted 72-kd metalloproteinase that specifically degrades type IV
      collagen as well as denatured collagens, has been implicated in smooth muscle
      cell migration. To evaluate the possible contribution of this enzyme to the
      formation and progression of the atherosclerotic lesion, the expression of MMP-2
      was studied in human aortic tissue. MMP-2 was visualized in frozen sections of
      the aortic wall by an immunofluorescent technique with a polyclonal antibody.
      Expression of MMP-2 in the aortic extracts was also studied by zymography and
      Western blotting. Our results reveal that a greater amount of MMP-2 is present in
      fatty streaks and atherosclerotic plaques as compared with normal regions of the
      aorta. Immunoblotting analysis showed that MMP-2 was expressed in atherosclerotic
      plaque > fatty streak > normal aortic wall in a ratio of approximately 4:2:1.
      Zymograms show that both forms (activated and latent) of MMP-2 increased in the
      atherosclerotic plaques. The presence of macrophages, detected by an
      immunohistochemical technique in some areas of higher MMP-2 expression suggests
      that these cells are a possible source of MMP-2. We conclude that MMP-2
      collagenase may have a role in the formation and progression of the
      atherosclerotic lesion and may be involved in clinical complications of
      atherosclerosis, such as fissure and rupture, leading to thrombosis.

PMID- 8546197
TI  - Antigen-presenting cell engineering. The molecular toolbox.

PMID- 8546200
TI  - Direct stimulation of limbal microvessel endothelial cell proliferation and
      capillary formation in vitro by a corneal-derived eicosanoid.
AB  - 12(R)-Hydroxyeicosatrienoic acid (12(R)-HETrE), a corneal epithelial derived
      inflammatory eicosanoid, elicits blood vessel growth into the avascular cornea in
      the classical corneal micropocket bioassay. Using an in vivo stimulated
      angiogenesis assay and 12(R)-HETrE as the angiogenic stimulus, we isolated a
      homogeneous population of rabbit limbal microvessel endothelial cells, the target
      for angiogenic factors in the anterior surface of ocular tissues, and analyzed
      the mitogenic and angiogenic potential of this eicosanoid. 12(R)-HETrE
      stereospecifically increased cell number by approximately 45%, an effect
      comparable to that of basic fibroblast growth factor (0.6 nmol/L; 10 ng/ml). This
      potent mitogenic response was maximal at 0.1 nmol/L. An additive effect
      (approximately 90% above control) on cell proliferation was observed when 12(R)
      HETrE (0.1 nmol/L) and basic fibroblast growth factor (0.6 nmol/L) were added to
      quiescent cultures of rabbit limbal microvessel endothelial cells. We also show
      that 12(R)-HETrE, but not 12(S)-HETrE, induces cultured rabbit limbal microvessel
      endothelial cells to organize themselves as a network of branching cords
      reminiscent of capillaries. This effect was evident within 48 hours, maximal by 5
      days of culture, and paralleled the effect observed with basic fibroblast growth
      factor. This study describes a novel method for testing site-directed
      angiogenesis in vitro and further strengthens the angiogenic properties of 12(R)
      HETrE by demonstrating a direct effect on limbal microvessel endothelial cells.

PMID- 8546201
TI  - Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart
      failure.
AB  - It is often speculated that progressive deterioration of left ventricular
      function in heart failure is due to ongoing loss of viable cardiocytes. In this
      study, we examined the possibility that cardiocyte loss in heart failure may be
      due, in part, to apoptosis, an active process of gene-directed cellular self
      destruction. Studies were performed in left ventricular tissue obtained from 10
      dogs with chronic heart failure produced by multiple intracoronary
      microembolizations (left ventricular ejection fraction 27 +/- 1%) and from 5
      normal dogs. Evidence for cardiocyte apoptosis was based on transmission electron
      microscopy criteria and on in situ immunohistochemical labeling of nuclear DNA
      fragmentation. There was no evidence of apoptotic cardiocytes in normal dogs.
      Features of cardiocyte apoptosis were observed in dogs with heart failure
      primarily in regions bordering old infarcts. Electron microscopic features of
      cardiocyte apoptosis included (1) intact sarcolemma and inner organelles in the
      presence of compaction and segregation of nuclear chromatin into sharply
      delineated masses that about the nuclear envelope, (2) intact sarcolemma in the
      presence of cytoplasm shrinkage, blebbing, and nuclear fragmentation, and (3)
      intact sarcolemma in the presence of complete disorganization of inner organelles
      and disappearance of nucleolemma. A count of all of the apoptotic bodies
      positively labeled for nuclear DNA fragments showed that 11% were of cardiocyte
      origin confirmed by positive labeling with striated muscle antimyosin antibody.
      We conclude that morphological and biochemical features of cardiocyte apoptosis
      exist in the left ventricular myocardium of dogs with chronic heart failure.

PMID- 8546202
TI  - Localization of type I procollagen gene expression in silica-induced
      granulomatous lung disease and implication of transforming growth factor-beta as
      a mediator of fibrosis.
AB  - We have used the silica-induced model of pulmonary injury in the rat to study the
      pattern of collagen expression in granulomatous lung inflammation. A single
      intratracheal instillation of silica into adult rats resulted in granulomatous
      inflammation leading to fibrosis and alveolar proteinosis. The development of
      disease in these animals was characterized over a 27-day period after treatment
      by means of histological, biochemical, and molecular analyses. Biochemical
      analyses indicated that significant increases in the weights of silicotic lungs
      were due to elevated amounts of DNA and total protein. Analysis of hydroxyproline
      content showed a 15-fold increase in this amino acid in silicotic lungs,
      confirming the development of a fibrotic reaction. In situ hybridization for type
      I procollagen mRNA displayed increased gene expression in the parenchyma,
      conducting airways, and vasculature of silicotic rats. Within the parenchyma,
      type I procollagen was expressed uniquely within granulomatous lesions.
      Immunohistochemistry indicated type I procollagen was being expressed by an alpha
      smooth muscle actin-negative population of cells. Immunolocalization of extra
      cellular transforming growth factor-beta showed coincident temporal and spatial
      overlap with type I procollagen expression, implicating this cytokine as a
      mediator of collagen gene expression in this model.

PMID- 8546204
TI  - Genotyping of Epstein-Barr virus in Brazilian Burkitt's lymphoma and reactive
      lymphoid tissue. Type A with a high prevalence of deletions within the latent
      membrane protein gene.
AB  - Both Epstein-Barr virus (EBV) types A and B are found in endemic Burkitt's
      lymphoma (BL) occurring in equatorial Africa. We studied 17 cases of Brazilian BL
      previously demonstrated to be EBV-positive to determine the EBV type as well as
      the presence of a characteristic 30 bp deletion within the 3' end of the latent
      membrane protein-1 (LMP-1) gene that may be important to the pathogenesis of
      several EBV-associated neoplasms. All cases in which the age was known were
      children. We found type A EBV in 13 of 14 (93%) evaluable cases, and type B in
      one case. The LMP-1 deletion was found in 12 of 15 (80%) evaluable cases,
      including the one case of type B EBV, and a similar high prevalence (59%) of the
      deletion was detected in EBV-positive normal and reactive lymphoid tissues from
      individuals from the same geographic region. The high proportion of cases
      associated with type A EBV suggests that immunodeficiency is not an important
      factor in the pathogenesis of Brazilian BL, in contrast to endemic African BL.
      The presence of the LMP-1 deletion in a high prevalence in the normal population
      in this region is unexplained.

PMID- 8546203
TI  - Constitutive expression of E-selectin and vascular cell adhesion molecule-1 on
      endothelial cells of hematopoietic tissues.
AB  - The first step in the homing of hematopoietic progenitor cells (HPCs) from the
      peripheral blood to the bone marrow involves an adhesion molecule-dependent
      contact with human bone marrow endothelial cells (HBMECs). In the present study
      we describe the constitutive expression of two of these molecules, E-selectin and
      vascular cell adhesion molecule-1 (VCAM-1), on endothelial cells of hematopoietic
      tissues. Immunophenotypic analysis of tissue sections of hematopoietically active
      (human adult and fetal bone marrow, fetal spleen, fetal liver, and adult spleen
      with extramedullary hematopoiesis) and inactive tissues (human adult spleen,
      lymph node, appendix, and liver; and fetal lung and fetal intestine) revealed
      that E-selectin and VCAM-1 are selectively expressed on endothelial cells of
      adult and fetal hematopoietic organs. These results were validated by means of
      reverse-transcriptase polymerase chain reaction. Adhesion studies revealed that
      binding of normal mobilized peripheral blood HPCs to HBMECs was completely
      inhibited by preincubation of HBMECs with anti-E-selectin (ENA2), whereas no
      effect of anti-VCAM-1 (1G11B1) was detected. These results suggest that E
      selectin plays a role in the homing of HPCs and that its constitutive expression
      on endothelial cells of hematopoietic organs may be essential in the initial step
      of the homing process.

PMID- 8546205
TI  - Induction of E-selectin-dependent leukocyte recruitment by mast cell
      degranulation in human skin grafts transplanted on SCID mice.
AB  - Previous in vitro data indicate that degranulation of human mast cells triggers
      the induction of endothelial molecules important in leukocyte adhesion. In vivo
      experimental systems have not previously existed, however, to determine whether
      human mast cell degranulation is sufficient stimulus for leukocyte recruitment.
      To study this question, neonatal foreskins were transplanted onto immunodeficient
      mice. The grafts contained physiological numbers of human dermal mast cells that
      could be degranulated by a number of secretagogues that activate mast cells by
      different mechanisms. Degranulation was associated with an inflammatory response
      characterized by edema, up-regulation primarily of microvessel E-selectin, and
      influx of neutrophils. Leukocyte emigration associated with mast cell
      degranulation was inhibited by a monoclonal antibody against human E-selectin.
      These data indicate that degranulation of human mast cells in the human/SCID
      mouse model provokes cellular inflammation in skin. The ability to significantly
      inhibit early leukocyte infiltration with an antibody against E-selectin in this
      model supports the hypothesis that this molecule plays an important role in mast
      cell-induced inflammation.

PMID- 8546206
TI  - Transforming and differentiation-inducing potential of constitutively activated c
      kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line.
AB  - Two mutations of c-kit receptor tyrosine kinase (KIT), valine-559 to glycine
      (G559) and aspartic acid-814 to valine (V814), resulted in its constitutive
      activation. To examine the transforming and differentiation-inducing potential of
      the mutant KIT, we used the murine interleukin-3-dependent IC-2 mast cell line as
      a transfectant. The IC-2 cells contained few basophilic granules and did not
      express KIT on the surface. The KITG559 or KITV814 gene was introduced into IC-2
      cells using a retroviral vector. KITG559 and KITV814 expressed in IC-2 cells were
      constitutively phosphorylated on tyrosine and demonstrated kinase activity in the
      absence of stem cell factor, which is a ligand for KIT. IC-2 cells expressing
      either KITG559 or KITV814 (IC-2G559 or IC-2V814 cells) showed factor-independent
      growth in suspension culture and produced tumors in nude athymic mice. In
      addition, IC-2G559 and IC-2V814 cells showed a more mature phenotype compared
      with the phenotype of the original IC-2 cells, especially after transplantation
      into nude mice. The number of basophilic granules and the content of histamine
      increased remarkably. KITG559 and KITV814 also influenced the transcriptional
      phenotype of mouse mast cell proteases (MMCP) in IC-2 cells. The expression of
      MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than
      in the original IC-2 cells. The results indicated that constitutively activated
      KIT had not only oncogenic activity but also differentiation-inducing activity in
      mast cells.

PMID- 8546207
TI  - Altered presynaptic protein NACP is associated with plaque formation and
      neurodegeneration in Alzheimer's disease.
AB  - We have recently identified, in the brain tissue of patients afflicted with
      Alzheimer's disease (AD), the non-A beta component of AD amyloid (NAC) as a new
      constituent of amyloid. NAC is derived from a larger precursor, NACP, a
      presynaptic protein. To better understand the role of NACP/NAC in the
      pathogenesis of AD, we used semiquantitative immunoblotting and combined double
      immunocytochemistry/laser scanning confocal microscopy to study the concentration
      and distribution of NACP/NAC in human brain, and compared them to the
      concentration and distribution of the presynaptic marker synaptophysin and the
      amyloid marker A beta. The semiquantitative immunoblotting demonstrated that the
      NACP concentration is slightly increased in the AD frontal cortex without
      statistical significance, whereas synaptophysin was reduced in its levels in AD.
      Consequently the proportion of NACP/synaptophysin was more than double in the AD
      frontal cortex as compared with controls. In the AD neocortex, NACP was
      colocalized with approximately 80% of the synaptophysin-immunoreactive structures
      (presumably the presynaptic terminals) and with the dystrophic neuritic component
      of the plaques. Computer-aided analysis showed that numbers of NACP
      immunoreactive structures along synaptophysin-immunoreactive structures were
      significantly diminished (30 to 40%) in AD. Although the overall numbers of NACP
      positive structures were decreased, there was a significant increase in the
      intensity of NACP-immunoreactivity per structure in AD. This increased intensity
      of NACP immunoreactivity per structure in AD was not observed with anti
      synaptophysin, consistent with immunoblotting-based quantification. Antibodies
      against NAC immunoreacted with amyloid in 35% of the diffuse plaques and 55% of
      the mature plaques. Normal aged control brains containing small groups of diffuse
      plaques were negative with anti-NAC. Double-immunolabeling studies with A beta
      antibodies showed that NAC immunoreactivity is more abundant in the center
      portion of amyloid rather than in the periphery. These studies suggest that there
      is a connection between metabolism of presynaptic proteins and amyloid formation,
      and that NAC might follow diffuse A beta accumulation resulting in the formation
      of compact amyloid and mature plaques.

PMID- 8546208
TI  - Transforming growth factor-beta 1 in experimental autoimmune neuritis. Cellular
      localization and time course.
AB  - Experimental autoimmune neuritis (EAN) is a monophasic inflammatory disorder of
      the peripheral nervous system that resolves spontaneously by molecular mechanisms
      as yet unknown. We have investigated whether the immunosuppressive cytokine
      transforming growth factor-beta 1 (TGF-beta 1) might be endogenously expressed in
      the peripheral nervous system of Lewis rats with actively induced and adoptive
      transfer EAN. TGF-beta 1 mRNA was upregulated to high levels in sensory and motor
      roots, spinal ganglia, and sciatic nerve as revealed by quantitative Northern
      blot analysis and in situ hybridization histochemistry, with peak levels just
      preceding the first signs of clinical recovery. TGF-beta 1 mRNA was localized to
      scattered round cells and dense cellular infiltrates, but only rarely to Schwann
      cell profiles. Double labeling studies revealed macrophages and subpopulations of
      T cells as the major cellular source of TGF-beta 1 mRNA. TGF-beta 1 protein was
      visualized immunocytochemically and localized to infiltrating mononuclear cells
      with peak expression around the same time as mRNA, in addition to some
      constitutive expression in axons and Schwann cells. Our studies suggest that the
      spontaneous recovery observed in Lewis rat EAN might be mediated by the
      endogenous elaboration of TGF-beta 1 within the peripheral nerve, and that
      macrophages might control their own cytotoxicity by expressing TGF-beta 1.

PMID- 8546210
TI  - Granzyme B expression in Reed-Sternberg cells of Hodgkin's disease.
AB  - Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic
      cells in Hodgkin's disease. Although most data suggest a lymphoid origin, the
      nature of these cells still remains the subject of considerable controversy.
      Recently, monoclonal antibodies became available, directed against granzyme B, a
      serine protease specifically expressed by activated cytotoxic T cells (CTLs) and
      natural killer (NK) cells. Using two granzyme B-specific antibodies directed
      against different epitopes, we studied the expression of granzyme B in a well
      characterized group of Epstein-Barr virus (EBV)-positive and EBV-negative cases
      of Hodgkin's disease. Granzyme B expression was found in part of the H-RS cells
      in 11 out of 61 tested cases (18%, 9 of 46 cases of nodular sclerosing and 1 of
      12 mixed cellularity Hodgkin's disease). In none of these cases did H-RS cells
      express B-cell markers, whereas in four cases, expression of either the T-cell
      marker CD3 or CD8 was found in a small minority of H-RS cells. The percentage of
      granzyme B-positive H-RS cells ranged from < 10% to > 50%. Granzyme B-positive H
      RS cells were present in 6 of 26 EBV-positive cases and in 5 of 35 EBV-negative
      cases, indicating no relationship with the presence of EBV. Moreover, no
      significant differences were found regarding either stage at presentation or
      clinical outcome. We conclude that in a restricted number of cases of Hodgkin's
      disease, the H-RS cells express granzyme B, and therefore might be considered the
      neoplastic equivalent of either activated CTLs or NK cells.

PMID- 8546209
TI  - Coexpression of hepatocyte growth factor and receptor (Met) in human breast
      carcinoma.
AB  - Expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR, product of
      the met proto-oncogene) mRNA were examined by nonisotopic in situ hybridization
      in a spectrum of benign and malignant human breast tissues. mRNA for both HGFR
      and HGF was detected in benign ductal epithelium. Epithelial expression of HGF
      mRNA was particularly intense in regions of ductal epithelial hyperplasia.
      Positive expression of HGF (but not HGFR) mRNA was also found in adipocytes,
      endothelial cells, and to varying degrees in stromal fibroblasts. In 12 of 12
      cases of ductal carcinoma in situ and infiltrating ductal carcinoma, carcinoma
      cells showed a heterogeneous pattern of expression for both HGFR and HGF mRNA. In
      infiltrating ductal carcinomas, intense expression of HGFR mRNA was not
      restricted to ductular structures but as also seen in non-duct-forming carcinoma
      cells. The same zones of the tumors (most commonly at the advancing margins) that
      expressed strongly HGFR mRNA often were also strongly positive for HGF mRNA,
      suggesting a possible autocrine effect. The expression pattern of HGFR protein in
      25 cases including the same series of tissues used for in situ hybridization
      analysis was similar to that of HGFR mRNA, as determined by an immunoperoxidase
      technique. The finding that HGFR is expressed by both benign and malignant
      epithelium, and its not restricted to duct-forming structures, suggests that,
      although the potential for HGF/HGFR binding is maintained in malignancy, the
      response to ligand binding at the level of the receptor or the cellular response
      to receptor activation may change at some point during progression.

PMID- 8546211
TI  - Effects of CD11b/18 monoclonal antibody on rats with permanent middle cerebral
      artery occlusion.
AB  - The progression of a lesion from ischemic injury to infarct, after the permanent
      occlusion of a middle cerebral artery, may be influenced by the influx of
      leukocytes into the ischemic territory. We aimed to evaluate the effectiveness of
      treating rats that had permanent middle cerebral artery occlusion with a single
      dose of an anti-CD11b/18 monoclonal antibody injected 1 hour after the arterial
      occlusion. To mimic the clinical situation of patients with ischemic strokes who
      may be treated within 1 hour of the ischemic event, the artery remained occluded.
      Forty-one adult Wistar rats had permanent middle cerebral artery occlusion, and
      one was subjected to a sham operation. One hour later, 22 rats received CD11b/18
      monoclonal antibody and an additional 20 were injected either with a nonspecific
      antibody (n = 10) or a buffer solution (n = 10). Experiments were terminated at
      intervals ranging 12 to 96 hours after the arterial occlusion. Endpoints included
      neurological testing, daily evaluation of body weight, counts of white blood
      cells in the peripheral blood, measurement of the area of pallor in the ischemic
      hemisphere, counts of necrotic neurons, and counts of leukocytes sequestered in
      the ischemic hemisphere. In experiments terminated 12 hours after the arterial
      occlusion (n = 4), there were fewer necrotic neurons in the group treated with
      the CD11b/18 monoclonal antibody compared with the two controls (P < .05), but
      this difference was not reflected in the neurological scores. Numbers of necrotic
      neurons in experiments terminated > 12 hours later were not different among the
      three subgroups. White blood cell counts in peripheral blood were lower in
      animals with arterial occlusion injected with the monoclonal antibody CD11b/18 (P
      < .05); numbers of leukocytes sequestered in the ischemic hemisphere were not
      different in the three groups. Neither changes in body weight nor in the volume
      of the area of pallor were significantly different among the three groups.

PMID- 8546212
TI  - Transient ischemia depletes free ubiquitin in the gerbil hippocampal CA1 neurons.
AB  - We investigated ubiquitin immunoreactivity in the post-ischemic gerbil
      hippocampus using a panel of ubiquitin antibodies. Immunostaining for ubiquitin
      in the hippocampus was strongly dependent on the antibodies used. With rabbit
      polyclonal antibody U-5379, immunoreactivity disappeared from the hippocampus in
      the early reperfusion period and reappeared in the dentate granule cells and CA3
      pyramidal cells but never in the CA1 pyramidal cells. In contrast, rat monoclonal
      antibody DF2 and mouse monoclonal antibody MAB1510 showed sustained
      immunoreactivity in the CA1 during the 48-hour reperfusion period. On the
      immunoblots of gerbil brain homogenates, three antibodies, U-5379, DF2 and
      MAB1510, exhibited similar specificities; all three labeled free ubiquitin most
      strongly. Immunoprecipitation disclosed that, under nondenaturing conditions, U
      5379 bound exclusively free ubiquitin, whereas DF2 and MAB1510 had little
      affinity for free ubiquitin but appeared to have more affinity for conjugated
      ubiquitin. Immunoabsorption of these antibodies with free ubiquitin confirmed the
      above result. It is most likely that U-5379 recognized free ubiquitin in the
      tissue, whereas DF2 and MAB1510 recognized preferentially conjugated ubiquitin.
      Thus, transient ischemia depletes free ubiquitin but not conjugated ubiquitin in
      the CA1. This depletion may be caused by impaired conversion from conjugated to
      free ubiquitin and/or failure of de novo ubiquitin synthesis.

PMID- 8546213
TI  - Galectin-3, a beta-galactoside-binding animal lectin, is a marker of anaplastic
      large-cell lymphoma.
AB  - Galectin-3 is a member of a newly named family of beta-galactoside-binding animal
      lectins, which has been described with a number of possible important biological
      functions, including the regulation of cell growth and association with tumor
      transformation. This protein has a wide tissue distribution but is notably not
      expressed by normal lymphocytes. We have previously shown that galectin-3 is
      markedly up-regulated in HTLV-I-infected T cells, most likely mediated by the
      viral transactivating protein Tax. In this study, we surveyed various lymphomas
      by immunohistochemistry and found the expression of galectin-3 in all of the 8
      cases of Ki-1+ anaplastic large-cell lymphoma (ALCL). Immunoreactivity for
      galectin-3 was found in a majority of the neoplastic cells in the ALCLs studied.
      In contrast, only 2 of the 35 cases of other types of lymphoma, including various
      Hodgkin's and non-Hodgkin's lymphomas, were positive. Unlike the cases of ALCL,
      immunoreactivity for galectin-3 in these 3 cases was found only sporadically in a
      small number of neoplastic cells. Thus, galectin-3 may prove to be a useful
      marker for ALCL and its expression in neoplastic cells in ALCL may contribute to
      the biological behavior of this specific type of lymphoma.

PMID- 8546214
TI  - Amyloid beta protein deposition in normal aging has the same characteristics as
      that in Alzheimer's disease. Predominance of A beta 42(43) and association of A
      beta 40 with cored plaques.
AB  - Two distinct species of amyloid beta protein (A beta) with different C-termini, A
      beta 42(43) and A beta 40, are deposited in senile plaques (SP) of Alzheimer's
      disease (AD), with the former being far predominant. To investigate whether A
      beta 42(43) also predominates over A beta 40 in normal aging, we examined by
      immunocytochemistry the C-termini of A beta in SP in the brains of non-demented
      aged individuals and compared the results with those in AD. Virtually all SP were
      A beta 42(43)-positive; of these 12% in non-demented aged individuals and 25% in
      AD patients (mean of three areas examined) were also A beta 40-positive. In both
      the AD and non-demented groups, 2/3 of the A beta 40-positive SP were typical
      cored SP. These results indicate that A beta 42(43) is the predominant species
      deposited in SP in normal aging, and there is no qualitative difference in terms
      of the C-terminus of A beta in the parenchymal amyloid deposition between normal
      aging and AD.

PMID- 8546215
TI  - Altered neurofilament expression does not contribute to Lewy body formation.
AB  - Lewy bodies (LBs) are cytoskeletal alterations found in several neurodegenerative
      disorders. Although neurofilaments are the main constituent of the LB, the
      precise mechanisms that underlie their formation remain speculative. To examine
      the pathogenesis of this inclusion, we measured the mRNA level of the low
      molecular weight neurofilament subunit in the nigral dopaminergic neurons of
      patients with LB disorders and neurologically normal controls. We found a small
      but significant decrease in the mean mRNA values in the LB group as compared with
      controls. However, a comparison of LB-bearing and non-LB-bearing neurons on the
      same section showed no significant difference between these two neuronal
      populations. We conclude that altered neurofilament expression is not a major
      contributory event in the pathogenesis of the LB. The decrease in neurofilament
      mRNA expression observed in the overall nigral dopaminergic neuronal population
      of LB disorders probably represents a nonspecific response to neuronal injury
      independent of LB formation.

PMID- 8546216
TI  - Copper/zinc superoxide dismutase expression in the human central nervous system.
      Correlation with selective neuronal vulnerability.
AB  - Oxidative stress has been implicated in the pathogenesis of several neurological
      disorders. We examined the regional distribution of copper/zinc superoxide
      dismutase (SOD-1), one of the key antioxidant enzymes, in the human central
      nervous system using in situ hybridization. Our results show that the enzyme is
      present at high levels of constitutive expression in alpha-motor neurons,
      oculomotor neurons, nucleus basalis, substantia nigra, neocortex, and the
      hippocampal sector resistant to hypoxia (H2). Relatively lower levels were found
      in Sommer's sector (H1) and Purkinje cells. We conclude that a lower constitutive
      level of SOD-1 expression may play a role in the selective vulnerability of
      certain neuronal populations to hypoxia but does not correlate with the patterns
      of neurodegeneration observed in amyotrophic lateral sclerosis. Parkinson's
      disease, and Alzheimer's disease.

PMID- 8546217
TI  - Spontaneously hypertensive rats develop pulmonary hypertension and hypertrophy of
      pulmonary venous sphincters.
AB  - This study explored the spontaneously hypertensive rat as an animal model of
      pulmonary hypertension and sought to identify anatomic changes in its pulmonary
      microvasculature, especially focal constrictions of pulmonary veins (sphincters).
      The average systemic and pulmonary artery blood pressures were 172/139 (+/- 9/9)
      and 36/14 (+/- 4/3), respectively, for spontaneously hypertensive Wistar Kyoto
      rats (SHR), and 134/83 (+/- 8/2) and 20/10 (+/- 2/2) for normotensive Wistar
      Kyoto rats (WKY) (P < 0.01 for both). Light microscopy of the lungs in SHR showed
      muscularization of both arteries and veins, but this was more pronounced in the
      small pulmonary veins. Perivascular edema was also present. There were 20 (+/- 4)
      leukocytes per 100 microns of capillary length in SHR and 9 (+/- 2) in WKY (P <
      0.001). Transmission electron microscopy showed focal venous smooth muscle was
      greater in SHR than in WKY. Scanning electron microscopy of vascular casts showed
      the average maximal focal venous contraction (sphincter) was 54% (+/- 10) of its
      diameter in SHR, but was only 6% (+/- 4) in WKY (P < 0.01). Arterial contraction
      occurred in the hypertensive rats as bourglass narrowings of the casts, but was
      less conspicuous than venous constrictions. The mean alveolar capillary diameter
      was 8.1 microns (+/- 1.6) in SHR, compared with 6.3 microns (+/- 1.0) in WKY (P <
      0.01). The central interspace between capillaries was 3.2 microns (+/- 1.6) in
      SHR and 6.0 microns (+/- 3.6) in WKY (P < 0.01). The venous contraction,
      capillary size, and capillary interspace distance correlated with the pulmonary
      blood pressure. The spontaneously hypertensive rat can be a model of pulmonary
      hypertension with its most notable structural change being increased muscularity
      in the small pulmonary veins.

PMID- 8546218
TI  - Antioxidant and oxidative stress changes during heart failure subsequent to
      myocardial infarction in rats.
AB  - Antioxidant enzyme activities and oxidative stress were evaluated in the
      myocardium in relation to hemodynamic function subsequent to myocardial
      infarction in rats. One week after the coronary ligation, the left ventricular
      peak systolic pressure, left ventricular end-diastolic pressure, and aortic
      pressures remained near control values and there were no differences in lung and
      liver wet/dry weight ratios between experimental and control animals. In the 4-,
      8-, and 16-week experimental animals, there was a progressive drop in left
      ventricular peak systolic pressure and an increase in left ventricular end
      diastolic pressure. Aortic systolic pressure was depressed at 8 and 16 weeks. In
      myocardial infarct rats, there was a significant increase in wet/dry weight ratio
      of lungs at 8 weeks and at 16 weeks; this ratio was increased for lungs as well
      as liver. Based on the hemodynamic data as well as other observations, animals in
      the 1-, 4-, 8-, and 16-week groups were arbitrarily categorized into nonfailure
      and mild, moderate, and severe failure stages, respectively. In the nonfailure
      stage, there was a marginal increase in superoxide dismutase, glutathione
      peroxidase, and catalase activities as well as vitamin E levels. The redox state
      in these hearts, assessed by the reduced/oxidized glutathione ratio, was
      significantly increased. Superoxide dismutase activity was unchanged in mild and
      moderate failure stages but significantly depressed at 16 weeks. Glutathione
      peroxidase and catalase activities showed progressive decreases through mild,
      moderate, and severe failure stages. Vitamin E levels were significantly
      depressed at moderate and severe failure stages. There was a progressive increase
      in lipid peroxidation at mild, moderate, and severe stages of heart failure and
      the redox ratio was significantly depressed in the severe failure stage. These
      data suggest that heart failure subsequent to myocardial infarction may be
      associated with an antioxidant deficit as well as increased myocardial oxidative
      stress.

PMID- 8546219
TI  - Interferon-inducible protein-10 is highly expressed in rats with experimental
      nephrosis.
AB  - Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family
      of chemotactic cytokines structurally related to interleukin-8. We have recently
      described the induction of IP-10 mRNA in mouse mesangial cells stimulated with
      lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further
      evaluate a possible role for this chemokine in renal injury, we have studied IP
      10 in an experimental model of nephrosis induced in rats by adriamycin. High
      levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial
      IP-10 protein were seen on day 21, coinciding with maximal proteinuria,
      glomerular tumor necrosis factor mRNA expression, and interstitial cellular
      infiltrates. Maintenance on a low protein diet not only delayed the appearance of
      proteinuria and interstitial cellular infiltrate but also decreased glomerular IP
      10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial
      and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with
      100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA
      expression was also inducible by lipopolysaccharide and cytokines in NRK 49F
      renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular
      epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial
      cells. We conclude that IP-10 is highly inducible in vitro and in vivo in
      resident glomerular and tubulointerstitial cells. IP-10 may participate in the
      modulation of renal damage in experimental nephrosis.

PMID- 8546220
TI  - Neuronal pattern correlates with the severity of human immunodeficiency virus
      associated dementia complex. Usefulness of spatial pattern analysis in
      clinicopathological studies.
AB  - The spatial distributional pattern of neurons, in the superior frontal gyrus of
      32 subjects who died of acquired immune deficiency syndrome, was examined. The
      patients were classified as nondemented, mildly demented, and severely demented,
      and some were treated with the anti-retroviral drug zidovudine. Spatial
      statistical techniques were employed to investigate the degree of clustering in
      the individual cases and various groups. We found that the cluster pattern of
      large and small neurons differed significantly with increasing severity of
      dementia but was not influenced by the duration of zidovudine treatment. We
      conclude that this is a sensitive technique for clinicopathological correlations
      and that the differences may result from loss of specific neuronal populations,
      which could determine the degree of dementia.

PMID- 8546221
TI  - MCF10AT: a model for the evolution of cancer from proliferative breast disease.
AB  - A human cell line (MCF10A) originated from spontaneous immortalization of breast
      epithelial cells obtained from a patient with fibrocystic disease. MCF10A cells
      do not survive in vivo in immunodeficient mice. However, T24 c-Ha-ras oncogene
      transfected MCF10A cells (MCF10AT) form small nodules in nude/beige mice that
      persist for at least 1 year and sporadically progress to carcinomas. By
      reestablishing cells in tissue culture from one of the carcinomas, a cell line
      designated MCF10AT1 was derived that forms simple ducts when transplanted in
      Matrigel into immunodeficient mice. With time in vivo, the epithelium becomes
      proliferative and a cribriform pattern develops within the xenografts. A
      significant number progress to lesions resembling atypical hyperplasia and
      carcinoma in situ in women, and approximately 25% progress to invasive carcinomas
      with various types of differentiation including glandular, squamous, and
      undifferentiated. Cells have been established in culture from lesions
      representing successive transplant generations. With each generation, cells are
      somewhat more likely to progress to high risk lesions resembling human
      proliferative breast disease. Although the incidence of invasive carcinoma
      remained fairly constant at 20 to 25%, the frequency of nodules showing
      proliferative breast disease rose from 23% in the first transplant generation to
      56% in the fourth transplant generation.

PMID- 8546222
TI  - Small epithelial cells and the histogenesis of hepatoblastoma. Electron
      microscopic, immunoelectron microscopic, and immunohistochemical findings.
AB  - The wide range of epithelial and mesenchymal lines of differentiation seen in
      hepatoblastoma suggests that this tumor derives from a pluripotent stem cell. To
      test this hypothesis, seven hepatoblastomas of various subtypes were investigated
      for the presence of cells with the features of the oval cells found during
      hepatocarcinogenesis in rodents that are thought to be closely related to hepatic
      stem cells. Because similar cells, referred to as "small cells," have been
      described in human liver disease with chronic ductular reaction, five liver
      biopsies from infants with biliary atresia were also investigated. The specimens
      were investigated by electron microscopy, immunoelectron microscopy, and
      immunostaining for cytokeratins 7, 8, 18, and 19. Small epithelial cells (SEC)
      corresponding to the oval cells of the rat and the "small cells" in humans were
      found in both biliary atresia and hepatoblastoma. These cells were oval and
      exhibited intercellular junctions, tonofilament bundles, and a biliary epithelium
      type cytokeratin profile. SEC were found in small numbers in fetal hepatoblastoma
      and in moderate numbers in embryonal hepatoblastoma. In small cell
      hepatoblastoma, nearly all the tumor cells exhibited SEC-like ultrastructural
      features and a corresponding cytokeratin profile. Thus, cells exhibiting
      morphological and immunophenotypic features of hepatic stem cells are detectable
      in hepatoblastoma. Their numbers vary according to the subtype, reflecting the
      differing degrees of differentiation of the various subtypes, consistent with the
      theory propounded in the literature that embryonal and, with further
      differentiation, fetal tumor cells derive from precursor small cells. The
      findings support the hypothesis that hepatoblastoma derives from a pluripotent,
      probably entodermal or even less committed, stem cell.

PMID- 8546223
TI  - Absence of exogenous interleukin-4-induced apoptosis of gingival macrophages may
      contribute to chronic inflammation in periodontal diseases.
AB  - Inflamed gingival tissues are enriched in macrophages (MOs) and CD4-positive T
      cells; however, T helper-type cytokines such as interleukin (IL)-2 and IL-4 are
      absent. Therefore, we investigated whether a relationship exists between IL-4
      receptor (IL-4R) expression and MO persistence in the absence of exogenous IL-4.
      Gingival MOs, when compared with monocyte(MN)/MOs from peripheral blood
      mononuclear cells, expressed high levels of IL-4R mRNA. Furthermore, in vitro
      cultures of gingival MOs remained viable whereas identically treated peripheral
      blood MN/MOs rapidly lost viability. However, when gingival MOs were incubated
      with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced. When
      the frequency of apoptotic cells was assessed in rIL-4-treated gingival MO
      cultures, higher numbers of apoptotic cells were noted in rIL-4-treated versus
      control cultures. Furthermore, rIL-4-treated MOs from inflamed gingiva showed DNA
      fragmentation as assessed by electrophoresis. These findings clearly show that
      addition of exogenous rIL-4 to gingival MO cultures leads to cell death by
      apoptosis. This finding would suggest that topical application of rIL-4 may
      inhibit the persistence of MOs in adult periodontitis, which could then lead to
      decreased inflammation.

PMID- 8546224
TI  - Beta-catenin expression in human cancers.
AB  - Cell-cell adhesion in tissue is mainly regulated by homotypic interaction of
      cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic
      proteins, including alpha- and beta-catenin. Although we previously demonstrated
      that alpha-catenin is crucial for cadherin function in vivo, little is known
      about the role of beta-catenin. We examined the expression of beta-catenin in
      human carcinoma samples along with normal tissue (esophagus, stomach, and colon)
      by immunostaining using our antibody for beta-catenin. Normal epithelium strongly
      expressed beta-catenin. However, beta-catenin expression was frequently reduced
      in primary tumors of the esophagus (10 of 15, 67%), stomach (9 of 19, 47%), and
      colon (11 of 22, 50%). From an immunoprecipitation study, we found that beta
      catenin forms a complex with E-cadherin not only in the normal epithelium but
      also in cancerous tissues. In coexpression patterns of E-cadherin and beta
      catenin, 43 (77%) of the 56 tumors showed a similar expression of both molecules,
      whereas the other 13 tumors (23%) showed positive staining for E-cadherin and
      reduced expression of beta-catenin. These findings suggest that beta-catenin
      forms a complex with E-cadherin in vivo and down-regulation of beta-catenin
      expression is associated with malignant transformation.

PMID- 8546225
TI  - Follicle-stimulating hormone receptor is expressed in human ovarian surface
      epithelium and fallopian tube.
AB  - The cellular expression of pituitary gonadotropin receptors in gonadal tissues is
      poorly defined because of the lack of suitable reagents. In this study, we
      developed in situ hybridization and reverse transcription polymerase chain
      reaction techniques for the evaluation of follicle-stimulating hormone receptor
      (FSHR) expression in the ovary and fallopian tube. Using a single-strand RNA
      probe, we demonstrated that FSHR mRNA expression is strongest in Graafian
      follicles. Within these developing follicles, granulosa cells showed the greatest
      expression, although both theca interna and theca externa were also positive,
      interna greater than externa. Granulosa cells in both primary and primordial
      follicles were positive, with primordial follicles showing only weak focal
      positivity. Ovarian surface epithelium and fallopian tube epithelium, not
      previously recognized to express FSHR, were both strongly positive. The FSHR
      expression in the ovary and fallopian tube was confirmed by reverse transcription
      polymerase chain reaction. Our results indicated that the FSHR is expressed in a
      cell-specific fashion at different stages of follicular development and is also
      expressed in ovarian surface and fallopian tube epithelia. The presence of FSHR
      in ovarian surface epithelium and of gonadotropin-binding sites in ovarian
      neoplasms provide additional evidence supporting the derivation of epithelial
      ovarian tumors from the surface epithelium and should promote heightened interest
      in the gonadotropin theory of ovarian tumorigenesis. More importantly, this study
      shows the feasibility of evaluating FSHR expression by both in situ hybridization
      and reverse transcription polymerase chain reaction. Application of these
      techniques to tumor specimens will help to elucidate the role of gonadotropins
      and their receptors in the carcinogenesis of gynecological tumors.

PMID- 8546227
TI  - Experimental coexpression of vimentin and keratin intermediate filaments in human
      melanoma cells augments motility.
AB  - Intermediate filaments have been used as cell-type-specific markers in
      differentiation and pathology; however, recent reports have demonstrated the
      coexpression of vimentin (a mesenchymal marker) and keratins (epithelial markers)
      in numerous neoplasms, including melanoma, which has been linked to metastatic
      disease. To test the hypothesis that coexpression of vimentin and keratins by
      melanoma cells contributes to a more migratory and invasive phenotype, we co
      transfected a vimentin-positive human melanoma cell line, A375P (of low invasive
      ability), with cDNAs for keratins 8 and 18. The resultant stable transfectants
      expressed vimentin- and keratin-positive intermediate filaments showed a two- to
      threefold increase in their invasion of basement membrane matrix and migration
      through gelatin in vitro. These findings were further corroborated by video
      cinematography. During attachment and spreading on fibronectin, the transfectants
      containing vimentin and keratins 8 and 18 demonstrated an increase in focal
      adhesions that stained positive for beta 1 integrin and phosphotyrosine, along
      with enhanced membrane ruffling and actin stress fiber formation. From these
      data, we postulate that coexpression of vimentin and keratins results in
      increased cytoskeletal interactions at focal contacts within extracellular
      matrices involving integrin cell signaling events, which contributes to a more
      migratory behavior.

PMID- 8546226
TI  - Induction of experimental bone metastasis in mice by transfection of integrin
      alpha 4 beta 1 into tumor cells.
AB  - Cell adhesion receptors (eg, integrins and CD44) play an important role in
      invasion and metastasis during tumor progression. The increase in integrin alpha
      4 beta 1 expression on primary melanomas has been reported to significantly
      correlate with the development of metastases. alpha 4 beta 1 is a cell surface
      heterodimer that mediates cell-cell and cell-extracellular matrix interactions
      through adhesion to vascular cell adhesion molecule (VCAM)-1 and to the IIICS
      region of fibronectin. To test the effects of alpha 4 beta 1 expression on tumor
      cell metastasis, Chinese hamster ovary cells were transfected with human alpha 4
      cDNA. Whereas alpha 4-negative Chinese hamster ovary cells developed only
      pulmonary metastasis, alpha 4-positive Chinese hamster ovary cells developed bone
      and pulmonary metastasis in 3 to 4 weeks when injected intravenously into nude
      mice. Bone metastasis was inhibited by antibody against alpha 4 or VCAM-1.
      Expression of alpha 3 beta 1, alpha 6 beta 1, or alpha V beta 1 did not induce
      bone metastasis. Expression of alpha 4 beta 1 also induced bone metastasis in
      K562 human erythroleukemia cells injected into SCID mice. These results
      demonstrate that alpha 4 beta 1 can induce tumor cell trafficking to bone,
      probably via interaction with VCAM-1 that is constitutively expressed on bone
      marrow stromal cells.

PMID- 8546228
TI  - Downregulation of microglial keratan sulfate proteoglycans coincident with
      lymphomonocytic infiltration of the rat central nervous system.
AB  - The monoclonal antibody (MAb) 5D4 against a keratan sulfate (KS) epitope of
      bovine cartilage proteoglycan stains ramified microglia in the rat brain. In this
      study we show that 5D4-positive microglia is abundant in the normal rat spinal
      cord and nearly absent during both the active and recovery phase of experimental
      autoimmune encephalomyelitis (EAE) in myelin-immunized Lewis rats. In contrast,
      during Wallerian degeneration of the optic nerve the density of KS-immunoreactive
      microglia remains constant. KS immunoreactivity is absent from both normal and
      transected sciatic nerves, and spinal nerve roots. On immunoblots of spinal cord
      extracts MAb 5D4 stains a novel type of KS proteoglycans (KSPGs) with an apparent
      molecular weight mainly between 140 and 200 kd, which significantly decrease in
      acute EAE. Our data suggest that high levels of KSPG expression correlate to a
      downregulated immunophenotype of resident macrophages in the nervous system. The
      lack of detectable KS in peripheral nerve points to a divergent differentiation
      of bone marrow-derived resident macrophages in the peripheral and central nervous
      systems and may partially account for the rapid macrophage response to axonal
      injury in the peripheral nervous system. Downregulation of microglial KSPG could
      be a prerequisite for a rapid inflammatory response in the central nervous
      system.

PMID- 8546229
TI  - beta PP and Tau interaction. A possible link between amyloid and neurofibrillary
      tangles in Alzheimer's disease.
AB  - Extracellular deposition of amyloid fibrils and intraneuronal accumulation of
      paired helical filaments (PHFs) are the neuropathological hallmarks of
      Alzheimer's disease. The major constituent of amyloid fibrils is a 39- to 43
      residue peptide (termed A beta), which is derived from a 695- to 770-amino-acid
      precursor protein (termed beta PP). The main component of PHFs identified so far
      is the microtubule-associated protein tau. Yet, there is no direct evidence of
      interconnection between these two pathological states. We report here that
      antibodies to an epitope located between residues 713 and 723 of beta PP770 (ie,
      the transmembrane region of beta PP distal to A beta) consistently labeled PHFs
      in the brain of Alzheimer patients. Solid phase immunoassay showed that a peptide
      homologous to residues 713 to 730 of beta PP770 bound tau proteins. This beta PP
      peptide spontaneously formed fibrils in vitro and, in the presence of tau,
      generated dense fibrillary assemblies containing both molecules. These data
      suggest that beta PP or beta PP fragments containing the tau binding site are
      involved in the pathogenesis of PHFs in Alzheimer's disease.

PMID- 8546230
TI  - E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19
      neuroglial cultures.
AB  - Lipid peroxidation increases with age in brain and is elevated further in
      Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of
      lipid peroxidation that can adduct and cross-link protein. Neurofibrillary
      tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain
      cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4
      hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins,
      including tau into high molecular weight species that were conjugated with
      ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross
      link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal
      was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and
      neurofibrillary tangle formation in Alzheimer's disease.

PMID- 8546232
TI  - The borderline patient: update on the diagnosis, theory, and treatment from a
      psychodynamic perspective.
AB  - This paper presents an overview regarding the borderline patient including
      historical background, diagnosis, developmental theory, prognosis, and
      psychotherapy, all from a psychodynamic perspective. The overview is succinct,
      current, and practical; it is comprehensive although certainly not all-inclusive.
      Five clinical vignettes are presented, reflecting various aspects of borderline
      patients. These vignettes are used to illustrate phenomena elaborated later in
      the paper. Regarding diagnosis, an approach based on ego strengths and ego
      weaknesses is detailed. This "ego-psychological diagnostic approach" leans on the
      ideas of Kernberg, but simplifies and occasionally modifies his work, in addition
      to including aspects of the borderline patient not stressed by him. It provides a
      simple, integrated summary of current psychodynamic diagnostic thinking. The
      paper compares and contrasts two of the most useful developmental theories
      regarding the borderline patient, those of Kernberg and Adler. The clinical
      usefulness of the two theories is noted, as is their relationship to etiology.
      Relying on the work of Stone, there is a brief section on prognosis, followed by
      an even briefer discussion of referral yield. The paper concludes with a
      discussion of psychotherapy. A continuum of psychodynamically related
      psychotherapies is detailed, then related to borderline individuals.

PMID- 8546231
TI  - Immunomagnetic separation can enrich fixed solid tumors for epithelial cells.
AB  - Immunomagnetic separation is a highly specific technique for the enrichment or
      isolation of cells from a variety of fresh tissues and microorganisms or
      molecules from suspensions. Because new techniques for molecular analysis of
      solid tumors are now applicable to fixed tissue but sometimes require or benefit
      from enrichment for tumor cells, we tested the efficacy of immunomagnetic
      separation for enriching fixed solid tumors for malignant epithelial cells. We
      applied it to two different tumors and fixation methods to separate neoplastic
      from non-neoplastic cells in primary colorectal cancers and metastatic breast
      cancers, and were able to enrich to a high degree of purity. Immunomagnetic
      separation was effective in unembedded fixed tissue as well as fixed paraffin
      embedded tissue. The magnetically separated cells were amenable to fluorescence
      in situ hybridization and polymerase chain reaction amplification of their DNA
      with minimal additional manipulation. The high degree of enrichment achieved
      before amplification contributed to interpretation of loss of heterozygosity in
      metastatic breast cancers, and simplified fluorescence in situ hybridization
      analysis because only neoplastic cells were hybridized and counted.
      Immunomagnetic separation is effective for the enrichment of fixed solid tumors,
      can be performed with widely available commercial antibodies, and requires little
      specialized instrumentation. It can contribute to interpretation of results in
      situations where enrichment by other methods is difficult or not possible.

PMID- 8546233
TI  - Unearthing shame in the supervisory experience.
AB  - A premise of this article is that the supervisee typically experiences shame in
      psychotherapy supervision. The purpose is to demonstrate that the discovery and
      exploration of shame by the supervisor and the supervisee enhance both the
      therapy and the supervision. The focus is on the supervisor's attitudes and
      behaviors toward the supervisee's shame. Using a case example, three important
      sources of that shame are discussed: (1) Shame that evolves from the relationship
      between therapist and patient. (2) Shame that arises from the therapist's fears
      of, or actual experience of, not being approved of or admired by an idealized
      supervisor. (3) Shame inherent in revealing personal material in a supervisory
      relationship. Six recommendations for exploring shame are offered to supervisors:
      (1) be alert to the therapist's disguised shame, (2) encourage the supervisee to
      explore how the therapy and supervision are experienced, (3) demonstrate the
      qualities of a psychotherapist by assisting the therapist in uncovering personal
      material that affects the psychotherapy, and (4) create an environment of safety
      where shame-related phenomena can be discussed with candor and curiosity.
      Supervisors should also (5) ease insecurities by modeling the activities they
      seek to encourage, and (6) avoid attempts to dissuade the supervisee of an
      idealizing transference toward them. Limitations of the recommendations are
      discussed.

PMID- 8546234
TI  - Interactional obstacles to empathic relating in the psychotherapy of narcissistic
      disorders.
AB  - Psychotherapy with narcissistic patients exposes therapists to a set of
      interactional pressures which threaten to disrupt the desired therapeutic stance
      of empathic relatedness. The therapeutic relationship is a field of unconscious
      mutual influence in which therapists' own narcissistic vulnerabilities are
      threatened by narcissistic patients' characteristic interpersonal style. A
      typical constellation of countertransference feelings and reactions is aroused,
      characterized by a temporary or chronic state of narcissistic symmetry between
      patients and therapists. In this relational state both patients and therapists
      unconsciously defend their respectively tenuous sense of self-esteem from the
      perceived threat posed by the other, using similar defensive narcissistic
      strategies. Unless this interactional narcissistic symmetry is diffused a
      therapeutic impasse ensues, which may jeopardize the therapeutic alliance. This
      potential is exacerbated in the case of those therapists with characterological
      narcissistic features, as they unconsciously require constant affirmation from
      their patients in order to enhance their deficient self-esteem. Enduring,
      understanding, and adaptively processing narcissistic countertransference
      responses facilitates the resumption of the desired empathic stance,
      characterized by an optimal condition of narcissistic asymmetry between
      therapists and patients.

PMID- 8546235
TI  - Psychotherapeutic discourse analysis.
AB  - Psychotherapeutic discourse analysis is a significant, largely unexplored, tool
      for psychotherapist and an ideal data sight for linguists. Increased
      multidisciplinary research in this area would be particularly fruitful.
      Conversations, including therapeutic conversations, are far from transparent
      conduits of information from one person to another. Complicating surface
      communication is "metacommunication," which takes the form of unconscious
      conversational styles--culturally influenced rules, norms, and expectations of
      how a conversation should proceed. If the therapist and the patient are working
      with different conversational styles, then blocks in communication and
      understanding are inevitable. Through discourse analysis conversational styles
      can become more available to awareness for use in the service of therapeutic
      goals. This paper is an example of a discourse analysis of an individual therapy
      session. I attempt to bridge the gap between broad psychodynamic treatment
      strategies and minute micro-conversational strategies that can be used to enhance
      the therapeutic process.

PMID- 8546236
TI  - The phenomena of Pine's "four psychologies": their contrast and interplay as
      exhibited in the Beatles' "white album".
AB  - Psychoanalytically informed clinicians are frequently challenged with recognizing
      and integrating into their work the diverse phenomena central to differing
      psychoanalytic theoretical frameworks. In addressing this dilemma, Pine has
      formulated a "multiple model" that recognizes the qualitatively different
      psychological phenomena and the distinct motivational forces emphasized by what
      he calls "the four psychologies of psychoanalysis," the psychologies of drive,
      ego, object relations and self. This model makes it possible to describe
      individual personality organizations in terms of psychological hierarchies of the
      phenomena of the four psychologies. Use of this model promotes a particular kind
      of listening stance that facilitates recognition and use of a wide variety of
      clinical data. The usefulness of this model is demonstrated through its
      application to a creative work, the Beatles' "White Album." This application
      shows the utility of Pine's psychological hierarchies in describing differing
      personality organizations, the "multiple functions" mental events can represent
      through serving the motives of multiple psychologies, and the frequent
      interactions that occur between the differing psychological phenomena. Pine's
      model facilitates a recognition that an important quality found in works by the
      Beatles is their demonstration in strikingly clear form, of the qualitatively
      different aspects of human experience emphasized by the four psychologies. The
      accessibility of Beatles music makes it a potentially valuable teaching tool for
      demonstrating Pine's model.

PMID- 8546237
TI  - The image of the psychotherapist in literature.
AB  - The current study explores the image of the psychotherapist as he/she is
      portrayed in literature in an attempt to broaden the perspective of existing
      research on this topic. In the past, studies and surveys on the image of
      psychotherapists have mainly been conducted among the general public and fellow
      colleagues rather than among the patients of psychotherapists. It is suggested
      that psychotherapists shy away from being the subjects of study. Moreover, it is
      proposed that research on the image of the psychotherapist suffers from a one-way
      gaze, whose bias stems from the asymmetrical nature of therapist-patient
      relationships. The present study explores the image of the psychotherapist
      through an analysis of nineteen literary works featuring twenty-six figures of
      psychotherapists. The literary image was examined by means of a questionnaire and
      content analysis. The profile that emerges suggests that psychotherapists and the
      psychotherapeutic process are well understood by authors representing both
      individual patients and the general public.

PMID- 8546238
TI  - The decision to remove homosexuality from the DSM: twenty years later.
AB  - Twenty years have passed since the American Psychiatric Association (APA) voted,
      in 1973, to remove "Ego-syntonic Homosexuality" from the Diagnostic and
      Statistical Manual of Mental Disorders (DSM). The present study investigates the
      influence of the patient's sexual orientation on the therapist's perception of
      the former's mental health. Four hundred and seventeen Israeli therapists
      (psychiatrists, clinical psychologists, and social workers) participated in the
      study, representing a cross-section of professionals in the mental health
      services in Israel. The measures included a demographic questionnaire and a
      perceived-severity scale of rating. Participants were assigned case histories
      where a hypothetical patient was heterosexual or ego-syntonic homosexual.
      Attributions of severity of mental status were found to differ as a function of
      sexual orientation of patient. Results are discussed in terms of the latent
      function of psychotherapy, considering the contrast between the liberal political
      attitudes and the secular way of life of the therapists on the one hand and their
      conservatism in the clinical domain on the other hand.

PMID- 8546239
TI  - The phallic child: its emergence and meaning in a clinical setting.
AB  - The nature of the drive toward forming and maintaining intense attachments with
      other human beings has been examined in the light of case material from the play
      therapy sessions of a ten-year-old boy. The primary question addressed concerns
      the relationship of the attachment drive to other drive systems. Freudian theory,
      object relations theory, and attachment theory present competing paradigms for
      understanding the relationship between the drives. The Freudian paradigm sees
      human attachment as derivative from other drives, especially the sexual drive. In
      developing his attachment theory, Bowlby broke from the classical Freudian view.
      He postulated attachment as a primary and autonomous drive. Object relations
      theory, by contrast, sees sexuality as one manifestation of a more fundamental
      drive that is intrinsically relationship seeking. Each of these traditions has
      contributed to our understanding of human reality. A careful examination of the
      clinical material, however, strongly suggests that a drive toward relationship is
      intrinsic to libidinal energy. It is therefore concluded that the understanding
      of the relationship between the drives based on object relations theory provides
      us with the most adequate framework within which to understand the clinical
      material.

PMID- 8546240
TI  - Consensus conference: Blood Management Surgical Practice Guidelines. Dallas,
      Texas, January 12-14, 1995.

PMID- 8546241
TI  - Establishing practice guidelines for surgical blood management.
AB  - Medical practice guidelines have been promoted as a way to improve the cost
      effectiveness of medical care. Algorithms for the transfusion of red blood cells,
      plasma, and platelets may be especially useful in the surgical setting if they
      incorporate point-of-care information that is both physiologic and patient
      specific for transfusion decision making. Therefore, the goals of guidelines for
      surgical blood management should be twofold. They should (1) acknowledge patient
      specific variability while addressing physician- and institution-dependent
      variables; and (2) improve blood component management by developing more
      physiologic clinical indicators of the need for allogeneic red blood cell
      transfusion.

PMID- 8546242
TI  - Allogeneic transfusion risks in the surgical patient.
AB  - The risk of blood transfusion-associated complications has been reduced in the
      past 10 years through technical advances in testing of blood, viral inactivation
      of noncellular blood components, enforcement of stringent donor selection
      criteria, and the use of alternatives to allogeneic transfusion. Even so, a zero
      risk blood supply is unfeasible. The general public perceives infectious
      complications to be the most significant risk: although the greatest fear is
      associated with transmission of human immunodeficiency virus (HIV), at least
      three hepatitis viruses are transmissible by all blood components. Human
      immunodeficiency virus accounts for < 20 cases per year of transfusion-related
      acquired immunodeficiency syndrome in the United States. The three important
      noninfectious complications are alloimmunization, which is common but clinically
      insignificant; immunosuppression, the clinical significance of which is
      controversial; and graft-versus-host disease, a lethal complication most likely
      to affect patients who are immunosuppressed, have cancer, or are recipients of
      bone marrow transplants.

PMID- 8546243
TI  - Legal considerations for allogeneic blood transfusion.
AB  - Our legal system seeks to resolve conflicts while also taking societal concerns
      into account. In striving for conflict resolution, the court performs a balancing
      act that weighs legitimate but differing individual and societal needs.
      Accordingly, in the preoperative setting, surgery patients are afforded the
      opportunity to accept or reject transfusions or alternatives to transfusion. The
      current legal standard is that alternatives to allogeneic transfusions should be
      offered to and carefully considered for patients. This article reviews blood
      shield laws, malpractice, and informed consent considerations in allogeneic blood
      transfusion. It also examines issues involved in refusal of transfusions. The
      discussion assumes that a physician-patient relationship exists and that the
      patient requires a surgical procedure in which blood loss is a reasonable
      probability. Guidelines are offered for preoperative physician-patient discussion
      of transfusion issues in light of the present status of transfusion law.

PMID- 8546244
TI  - Surgical red blood cell transfusion practice policies. Blood Management Practice
      Guidelines Conference.

PMID- 8546245
TI  - Morbidity risk assessment in the surgically anemic patient.
AB  - Clinicians have few data on which to base a decision to transfuse a surgical
      patient. We reviewed animal and human data to evaluate the effects that anemia
      and comorbidity have on surgical outcome. Experimental evidence consistently
      demonstrates increased cardiac output, decreased peripheral vascular resistance,
      and increased release of oxygen by red blood cells in response to anemia. Normal
      animals tolerate hemoglobin (Hb) levels down to approximately 5 g/dL. Below this
      level, cardiac ischemia and decreased ventricular function develop. In animals
      with experimental coronary artery stenosis, cardiac ischemia develops at Hb
      levels of 7-10 g/dL. Coexisting left ventricular hypertrophy, use of beta
      blockers, and hypoxemia also reduce animals' ability to tolerate anemia. The
      limited information on anemia tolerance of human surgical patients suggests that
      the presence of cardiac and pulmonary disease should influence transfusion
      decisions. A higher Hb threshold should be used in patients who have or are at
      risk of cardiac or pulmonary artery disease.

PMID- 8546246
TI  - Erythropoiesis, erythropoietin, and iron metabolism in elective surgery:
      preoperative strategies for avoiding allogeneic blood exposure.
AB  - Preoperative autologous donation (PAD) of blood and administration of recombinant
      human erythropoietin (Epoetin alfa) are two strategies for increasing red blood
      cell (RBC) mass preoperatively. The success of PAD depends primarily on the
      patient's ability to manufacture new RBCs before surgery to replace those removed
      during PAD. Red blood cell manufacture depends in turn on adequate supplies of
      iron and the increased renal production of endogenous erythropoietin following
      PAD. Successful PAD also requires adequate time for regeneration of predonated
      RBCs. Parenteral administration of Epoetin alfa causes a dose-dependent
      stimulation of RBC production. Its use has been studied as an adjunct to PAD and
      as a method to enhance endogenous erythropoiesis without PAD. Several studies
      suggest that administration of Epoetin alfa, begun several days before surgery,
      may stimulate erythropoiesis and help decrease the number of RBC transfusions
      required postoperatively. The precise role of Epoetin alfa in the surgical
      setting is not yet established, and optimal dosage regimens have not been
      determined.

PMID- 8546247
TI  - A physiologic basis for red blood cell transfusion decisions.
AB  - Identification of a universal "transfusion trigger" has eluded surgeons for
      years. Optimization of cardiopulmonary hemodynamics should precede the decision
      to transfuse red blood cells. Red blood cell transfusion should be considered
      when global oxygen delivery falls below a critical point with increasing oxygen
      extraction and lactate levels. At present, these parameters must be monitored
      with invasive techniques. This article addresses some aspects of global oxygen
      delivery physiology that appear to correlate with cardiac function, metabolism,
      and tissue perfusion.

PMID- 8546248
TI  - Alternatives to allogeneic blood use in surgery: acute normovolemic hemodilution
      and preoperative autologous donation.
AB  - Acute normovolemic hemodilution (ANH) is a common blood conservation strategy in
      elective surgical procedures. Moderate ANH is safe in patients > 60 years of age;
      ANH is not recommended for patients who have coronary artery disease, significant
      anemia, renal disease, severe hepatic disease, pulmonary emphysema, or
      obstructive lung disease. Preservation of oxygen delivery during ANH depends on
      the maintenance of normovolemia to avoid decompensation and falling cardiac
      output. Preoperative autologous donation (PAD) as a blood conservation strategy
      has the advantage of protecting the patient from risks associated with allogenic
      transfusion, but it is expensive and time consuming. No protocols have
      established a preference for either ANH or PAD; an early study suggested that ANH
      is less expensive and more effectively preserves blood components, but other
      researchers warn that the methodology for ANH remains unresolved.

PMID- 8546249
TI  - Conservation of blood during cardiovascular surgery.
AB  - Conservative use of allogeneic red blood cell (RBC) transfusion is a growing
      trend in cardiovascular surgery. Recent advances in blood conservation measures
      have reduced, and in some cases eliminated, the need for allogeneic RBC
      transfusions in some of these patients. Reduced reliance on allogeneic RBC
      transfusion requires close collaboration among the clinical pathology,
      anesthesia, and surgery services managing the patient. Preoperative conservation
      measures include donation of autologous blood and treatment with recombinant
      human erythropoietin (Epoetin alfa). Meticulous surgical technique, moderate
      hemodilution, aprotinin, hemostatic techniques, blood salvage, and
      autotransfusion are intraoperative measures that can reduce blood loss.
      Postoperatively, even severe blood deficits can often be restored with adequate
      diet and rest and the use of actinics.

PMID- 8546250
TI  - Blood management in orthopedic surgery.
AB  - The orthopedic surgeon has several options available for blood conservation.
      Preoperative autologous donation (PAD) of blood is a cost-effective measure when
      the cost of managing transfusion-transmitted infectious disease is considered;
      overuse and underuse are expensive problems, however. Hemodilution, while used
      successfully in prostate surgery, is logistically impractical in joint
      replacement centers. Intraoperative blood salvage, although costly, is useful in
      orthopedic procedures when the anticipated blood loss is > 1,000 mL. Reinfusion
      of postoperative drainage that has been filtered and washed is being used in some
      orthopedic procedures. Studies are under way to determine whether this method of
      blood conservation alters transfusion requirements. Recombinant human
      erythropoietin (Epoetin alfa) has a role in elective procedures with significant
      blood loss, including complex revision joint replacement, bilateral joint
      arthroplasty, and spinal fusion. Preoperative Epoetin alfa administration
      enhances preoperative autologous blood collection and increases perioperative red
      blood cell mass.

PMID- 8546251
TI  - Ten strategies to reduce blood loss in orthopedic surgery.
AB  - In any operative procedure, careful surgical dissection with precise hemostasis
      is one of the most effective ways to minimize surgical blood loss and reduce the
      need for allogeneic red blood cell transfusion. Several other techniques
      contribute to reduce blood loss in major orthopedic procedures. These techniques
      are reviewed and include rehearsal of the procedure and positioning the patient
      to reduce venous engorgement. In addition, a case report is presented that
      demonstrates the feasibility of revision hip replacement surgery without the use
      of transfusion in a Jehovah's Witness patient.

PMID- 8546252
TI  - Blood conservation strategies to minimize allogeneic blood use in urologic
      surgery.
AB  - Analysis of the net costs, efficacy, and cost-effectiveness of preoperative
      autologous blood donation (PAD), versus acute normovolemic hemodilution (ANH), in
      patients undergoing radical prostatectomy is presented. Currently, PAD is a
      standard of care for patients undergoing radical prostatectomy. Comparison of PAD
      with ANH showed no differences in risks or outcome, but ANH was less expensive.
      Hemodilution is a simple, safe, convenient, and effective alternative to PAD. The
      use of recombinant human erthropoietin in conjunction with PAD and ANH has
      optimized perioperative hematocrits and further minimized exposure to allogeneic
      blood. Intraoperative blood salvage, lower transfusion triggers, and other blood
      conservation strategies are discussed. The most cost-effective techniques
      currently available for decreasing allogeneic blood transfusions appear to be
      avoidance of blood loss, increased tolerance for decreased HCT levels, and
      autologous blood procurement via ANH.

PMID- 8546254
TI  - Composite tabulation of deaths in Anchorage, 1985-1988.

PMID- 8546253
TI  - Health effects of methyl tertiary butyl ether (MTBE) in gasoline in Alaska.
AB  - OBJECTIVES: This ecologic study assessed whether there was a change in health
      status in Alaska in the winter of 1992-93 after the introduction of MTBE in
      gasoline. Methyl tertiary butyl ether(MTBE) is used as a fuel oxygenate in the
      United States and in Europe. In the winter of 1992-93 MTBE was added to gasoline
      in the cities of Fairbanks and Anchorage, Alaska. The program was discontinued in
      Fairbanks in December, 1992, but continued in Anchorage until February 28, 1993.
      METHODS: Outpatient visits for state employees and dependents (n = approximately
      28,000) living in Alaska were compared over three winters by analyzing health
      insurance claims. RESULTS: Odds ratios were calculated. The odds ratios indicated
      that the winter of 92-93 was not statistically different from previous winters in
      numbers of claims for upper respiratory illness, bronchitis, headache, or asthma
      in either Anchorage or Fairbanks. CONCLUSION: There was no increase in claims for
      respiratory illness in either city after introduction of MTBE.

PMID- 8546255
TI  - Case history. Breast asymmetry: unusual presentation.

PMID- 8546256
TI  - Sexually speaking ... the dance.

PMID- 8546257
TI  - Syphilis control in Russian America--1 (1845).

PMID- 8546258
TI  - Samuel J. Call, M.D.--1858-1909.

PMID- 8546259
TI  - Painless herpes zoster.

PMID- 8546260
TI  - Prevalence of alcohol and illicit drug use by expectant mothers.
AB  - BACKGROUND: Prevalence data of illicit drug and alcohol use during pregnancy in
      Alaska is limited. This study demonstrates the prevalence of perinatal drug and
      alcohol use at a single community hospital in Anchorage, Alaska. METHODS: A
      convenience sample was used during a six month period. 351 anonymous urine
      samples were obtained from imminently delivering women. Screening toxicology
      tests were run and results were linked to demographic variables using a common
      random reference number. RESULTS: 16.2% (n = 57) of the samples were positive for
      drugs or alcohol. Cannabinoids and alcohol were found most frequently. Polydrug
      use was found in 22.8% of the positive samples. Medicaid recipients represented
      the highest users of illicit drugs and alcohol. CONCLUSIONS: The prevalence of
      positive drug screens and polydrug use in our sample is amongst the highest
      reported in the literature. The high prevalence of drug and alcohol use indicates
      that present prevention strategies are not working in Alaska. New and innovative
      outcome based strategies to decrease drug and alcohol use in pregnancy are
      needed.

PMID- 8546261
TI  - Collaborative visual rehabilitation: high astigmatism, esotropia and elevator
      palsy.

PMID- 8546262
TI  - Ocular complication in HIV infected individuals.
AB  - The incidence of acquired immunodeficiency syndrome is growing within all levels
      of Alaskan society. All physicians will be touched in some manner by this
      epidemic and there is a growing need for a thorough understanding of all aspects
      of the human immunodeficiency virus and acquired immunodeficiency syndrome.
      Visual complications associated with this disease are devastating, common, and in
      many cases treatable. The following discussion is an overview, in outline form,
      of the ocular complications associated with the human immunodeficiency virus and
      acquired immunodeficiency syndrome.

PMID- 8546263
TI  - Clinical diagnosis of wheezing in early childhood.

PMID- 8546264
TI  - Statement on self-monitoring of peak expiratory flow in the investigation of
      occupational asthma. Subcommittee on Occupational Allergy of the European Academy
      of Allergology and Clinical Immunology.

PMID- 8546265
TI  - A prospective study of cancer incidence in a cohort examined for allergy.
AB  - In order to assess the association between atopy and cancer risk, a cohort of
      6593 skin-prick-tested patients was established. Among atopic subjects, no
      overall increased cancer risk was found, but the incidence of both breast cancer
      (standardized incidence ratio (SIR) 2.50, 95% CI 1.01-5.16) and malignant
      lymphomas (SIR 4.40, 95% CI 1.20-11.3) was significantly enhanced. Atopic
      subjects with asthma showed a decreased overall cancer risk (SIR 0.73, 95% CI
      0.27-1.60), as compared with the other asthmatic subjects (SIR 1.46, 95% CI 1.03
      2.04). The cancer risk for subjects with rhinitis was near unity (SIR 1.11),
      irrespective of whether the subjects were atopic or not. An almost significant
      risk increase for cancer was observed among subjects with urticaria (SIR 1.70,
      95% CI 0.99-2.80). Our results support neither the original hypothesis of an
      overall cancer protective effect of atopy, nor that of an opposite effect;
      rather, they strengthen the view that the association between atopic diseases and
      cancer is complex.

PMID- 8546266
TI  - Neonatal IgA and IgE levels among infants with paternal heredity for atopic
      disease.
AB  - Serum IgA and IgE levels were studied in the postnatal period in 21 infants
      having a paternal heredity of atopic disease. Three different sampling techniques
      were used, aspirated cord blood (CB), gravity-collected cord blood, and capillary
      collected blood at 4-5 days of age. Significant differences among the three
      sampling techniques were recorded for IgA (P < 0.01), but not for IgE. The IgA
      levels decreased from birth to 4-5 days of age in 90% (19/21 of infants (P <
      0.01). The corresponding decrease in IgE levels was 20%. This postnatal
      difference in the frequency of decreasing/increasing IgA and IgE levels was
      significant (P < 0.05). An analysis of CB IgA to detect maternal contamination of
      CB was found to be of questionable value, since only 50% (2/4) of the cases with
      an elevated CB-IgA level could be considered contaminated. The results of this
      study further emphasize that aspiration of CB and capillary collection of blood
      at 4-5 days of age are the best sampling techniques to avoid contamination. The
      general finding that paternal heredity had no significant influence on infant IgE
      contrasts with the strong influence of maternal heredity. Further studies will
      show whether the explanation lies in genetic or transplacental factors, or in
      both kinds of factors.

PMID- 8546267
TI  - Increased frequency of bronchial hyperresponsiveness in patients with
      inflammatory bowel disease.
AB  - Although bronchopulmonary manifestations are rare in inflammatory bowel disease
      (IBD), subclinical abnormalities have been described in up to 50% of cases. The
      pathophysiology of these abnormalities remains unknown. However, a latent
      inflammation of the bronchial mucosa secondary to the inflammation of the
      intestinal mucosa has been suggested. This subclinical inflammation may lead to
      increased bronchial responsiveness. We studied the bronchial responsiveness in 38
      inflammatory bowel disease (IBD) patients, using the methacholine test. Bronchial
      hyperresponsiveness was defined by a PC20M < 16 mg/ml. Twenty-four healthy
      controls were also studied. There was no significant difference in baseline FEV1
      between IBD patients and controls. However, there was a significantly greater
      fall in FEV1 in the IBD patients at the concentrations of methacholine tested.
      The frequency of bronchial hyperresponsiveness was significantly higher in the
      IBD population (45%) than in controls (17%; P < 0.03). Atopy, defined by skin
      test, was more common in IBD patients (42%) than in controls (21%). Even when
      only nonatopic subjects were considered, the frequency of bronchial
      hyperresponsiveness was significantly higher in IBD patients (41%) than in
      controls (5%; P < 0.02). Thus, subclinical bronchial hyperresponsiveness is
      common in IBD, and may be considered a further extraintestinal manifestation.

PMID- 8546268
TI  - Comparison of IgE and IgG antibody responses of atopic individuals with
      sensitization to tree and grass pollens.
AB  - Sera of atopic individuals with predominant sensitization to either tree pollen
      (TAs) or tree and grass pollens (TGAs) as well as of nonatopic subjects (NAs)
      were analyzed for IgE, IgG, and IgG4 antibodies specific for grass pollens
      allergens. Of 600 atopic individuals with serum IgE antibodies specific for birch
      pollen allergens, 54% also had serum IgE antibodies specific for grass pollen.
      The mean titers of IgG antibodies specific for grass pollen proteins were about
      10 times higher in the sera of TGAs than those in the TAs and NAs. SDS-PAGE
      immunoblotting analysis of grass pollen proteins using sera of TGAs, TAs, and NAs
      with respect to the binding of these proteins with IgE and IgG antibodies in
      these sera exhibited a similar pattern of variation. Quantitation by enzyme
      immunoassay of the antibody binding to a recombination grass pollen allergen,
      rKBG8.3, further demonstrated the elevated IgG antibody levels in TGAs are mainly
      due to a broader range of specificities, and not to high specific binding to the
      individual protein. Statistically significant correlation was found between IgE
      and IgG4 antibodies specific for the Kentucky bluegrass (KBG) extract, but not
      for the isolated recombinant allergen. These results indicate that the grass
      pollens elicit a complex array of antibody specificities in both atopics and
      nonatopics, and that the profile of antibodies specific to the pollen extract and
      pure allergens differs, suggesting that single grass allergens may be inadequate
      for replacing grass pollen extracts for immunotherapy.

PMID- 8546269
TI  - Cross-sensitivity among oxicams in piroxicam-caused fixed drug eruption: two case
      reports.
AB  - Fixed drug eruption (FDE) caused by oxicams is very rare. There are few reports
      of FDE induced by piroxicam, and this explains why cross-sensitivity among
      oxicams (piroxicam, tenoxicam, and droxicam) has been studied in only one
      patient. The patch test on residual lesions has lately been used by some authors
      in FDE diagnosis with variable results. We describe two cases of piroxicam-caused
      FDE and demonstrate cross-sensitivity among piroxicam, tenoxicam, and droxicam in
      both of them. One patient had residual lesions and the patch test was useful for
      diagnosis and cross-sensitization studies. The second patient had no residual
      lesions, and the patch test was negative on normal but previously affected skin;
      therefore, the study was performed by single-blind controlled oral challenge.

PMID- 8546270
TI  - Positivity of patch tests in cutaneous reaction to aminocaproic acid: two case
      reports.
AB  - We observed two cases of maculopapular eruption occurring 12-72 h after the
      administration of aminocaproic acid (ACA). Patch tests performed with ACA were
      positive. Clinical and allergologic patterns suggest the type IV mechanism of
      hypersensitivity. We present what we believe are the first two cases described of
      hypersensitivity to this drug.

PMID- 8546271
TI  - Human seminal plasma anaphylaxis (HSPA): case report and literature review.
AB  - Human seminal plasma anaphylaxis (HSPA) is rare but may be life-threatening. The
      antigen or antigens involved in these reactions reside in a glycoprotein fraction
      of human seminal plasma (HSP). We report a woman who experienced HSPA. Literature
      on the subject is reviewed.

PMID- 8546272
TI  - Diagnostic value of the nasal provocation test with Dermatophagoides
      pteronyssinus in childhood asthma.
AB  - We aimed to determine whether the nasal provocation test (NPT) with allergen
      could be used as a diagnostic test in asthmatic children with or without allergic
      rhinitis, and whether it had any effects on pulmonary function tests and arterial
      oxygen saturation (SaO2) values. Therefore, 25 asthmatic outpatients sensitive to
      Dermatophagoides pteronyssinus (Dp), aged 6-17 years, 12 having allergic
      rhinitis, and 10 nonatopic children as a control group were challenged
      intranasally with solution containing Dp extract by administration of a total
      dose of 800-1000 AU to both nasal cavities. Before the test and 10 min and 20 min
      after the administration of the allergen intranasally, the nasal expiratory peak
      flow (NEPF), pulmonary function tests, and SaO2 were measured. In the NPT, a
      decrease of 20% or more in NEPF and occurrence of nasal symptoms were considered
      to be positive. NPT was positive in all the asthmatic patients with or without
      allergic rhinitis, while all the children in the control group had a negative
      test. Compared to values prior to the test, values of FEV1 (forced expiratory
      volume in 1 s) and SaO2 showed no statistically significant decrease, and no
      clinically significant asthmatic reaction was observed in any of the groups. Our
      study suggests that in asthmatic children with or without allergic rhinitis, the
      NPT with allergen is a simple, safe, and useful diagnostic test.

PMID- 8546273
TI  - Prevalence of asthma and asthma symptoms in a general population sample from
      northern Italy. European Community Respiratory Health Survey--Italy.
AB  - The European Community Respiratory Health Survey is an international survey of
      the general population which aims to establish whether there are significant
      variations in the prevalence of asthma among European countries. The present
      paper reports the prevalence of asthma and asthma-like symptoms in a sample of
      subjects living in three areas of northern Italy: Turin, Pavia, and Verona.
      Samples of residents 20-44 years old (3000 subjects in Turin and Verona and 1000
      in Pavia) stratified by sex (M:F = 1/1) were randomly selected from local health
      authority lists in the three participating areas. To correct the observed
      prevalence estimate for nonresponse bias, a method proposed by Drane was applied.
      Of the sampled subjects, 86% (6031) participated in the survey. Two different
      definitions of asthma were adopted: 1) prevalence of asthma attack in the last 12
      months; 2) prevalence of asthma attack or treatment with antiasthmatic drugs, or
      both wheezing apart from the common cold and wheezing with shortness of breath.
      This combination of symptoms has been called current asthma. According to these
      definitions, the prevalence of asthma attack was 3.47% (3.74% in men and 3.14% in
      women), and the prevalence of current asthma was 5.01% (5.07% in men and 4.90% in
      women). The lowest prevalence was found in Pavia; the highest in Turin. Our
      findings support the hypothesis that the difference in prevalence reflects the
      difference in mortality.

PMID- 8546274
TI  - Induction of nitric oxide synthase in a model of allergic occupational asthma.
AB  - We have studied the induction of nitric oxide during late allergic responses,
      using a guinea pig model of trimellitic anhydride (TMA)-induced airway allergy.
      TMA is a low molecular weight chemical which can cause occupational asthma. The
      activity of nitric oxide synthase (NOS) was investigated by the detection of 3H
      labeled citrulline formation from 3H-labeled arginine. In sensitized animals,
      challenge with TMA conjugated to guinea pigs albumin (TMA-GPSA) increased the
      activity of Ca(2+)-independent NOS (inducible NOS; iNOS) in lung and bronchial
      tissues at 15-17 h after challenge compared to nonsensitized animals. The
      induction of iNOS activity was associated with an associated with an increased
      level of nitrite, an end metabolite of the l-arginine-NO pathway, in
      bronchoalveolar lavage fluid. In contrast to iNOS, the activity of Ca(2+)
      dependent NOS (constitutive NOS; cNOS) was not affected by the allergen
      challenge. These results demonstrate that iNOS in bronchial tissue is induced
      late after allergen challenge in sensitized guinea pig.

PMID- 8546275
TI  - Allergen nomenclature.

PMID- 8546276
TI  - Neural-immune-effector trophobiology: possible psychologic implications in the
      allergic patient.

PMID- 8546277
TI  - Near infra-red spectroscopy.

PMID- 8546278
TI  - Health and activity after intensive care.
AB  - All patients discharged from a general intensive care unit over a 4.5 year period
      were sent a questionnaire 3 months after discharge which investigated aspects of
      their health and physical abilities. Replies were compared on the basis of age,
      diagnosis and sickness severity on admission. Five hundred and four
      questionnaires were analysed. Overall, 47% of patients described their health as
      good/very good, 42% as fair and 11% as poor/very poor. Activity level, compared
      to that before their admission, was unchanged in 59%, worse in 33% and improved
      in 8% of patients. There were no differences in health status or changes in
      activity with age, diagnosis or severity of sickness. Patients aged 76 years or
      older were more likely to perceive their health as 'better than average' than
      younger patients (p < 0.01). Eight percent of patients would be unwilling to
      undergo intensive care again. An unacceptable health status after intensive care
      cannot be predicted in any group of patients.

PMID- 8546279
TI  - Relationship of admission thyroid function tests to outcome in critical illness.
AB  - One hundred and eighty patients had serum thyrotropin, total triiodothyronine and
      free thyroxine concentrations measured within 3 h of admission to the Intensive
      Therapy Unit to assess whether thyroid function tests could predict outcome in
      critical illness. Overall mortality was 30.6%. Nonsurvivors were older (p =
      0.001), and had higher APACHE II scores (p < 0.001) and predicted mortalities (p
      < 0.001). There was no difference in the median values of thyrotropin, total
      triiodothyronine and free thyroxine concentrations between survivors and
      nonsurvivors. Thyrotropin concentration was subnormal in 15 patients, normal in
      152 and elevated in 13 patients. In contrast, 80 patients had subnormal
      triiodothyronine concentration. Free thyroxine was subnormal in five patients.
      Thyrotropin, total triiodothyronine and free thyroxine concentrations were not
      related to outcome (p = 0.360, p = 0.622, p = 0.726, respectively). No variable
      independently predicted death. Total triiodothyronine concentrations were lower
      in patients who received dopamine before admission to the intensive therapy unit
      than those who did not (p = 0.008); thyrotropin and free thyroxine concentrations
      were not influenced by dopamine administration. Serum concentrations of
      thyrotropin, total triiodothyronine and free thyroxine measured within 3 h of
      admission to the intensive therapy unit are not predictive of outcome.

PMID- 8546280
TI  - Pressure support ventilation during isoflurane anaesthesia.
AB  - We have studied the respiratory effects of 5 and 10 cmH2O pressure support
      ventilation during anaesthesia with 1.5% end-tidal concentration of isoflurane in
      nine healthy, spontaneously breathing, adult patients. Some of the patients
      demonstrated an irregular respiratory pattern with periods of apnoea and we
      therefore went on to study a further seven patients with a continuous 500 s
      recording of airflow. Pressure support ventilation augmented mean (SD) tidal
      volume from 212 (56) ml to 360 (88) ml at 5 cmH2O and to 509 (108) ml at 10 cmH2O
      (n = 16, p < 0.05). Mean (SD) respiratory rate decreased from 26 (6) min-1 to 22
      (6) min-1 at 5 cmH2O and 17 (5) min-1 at 10 cmH2O pressure support (n = 16, p <
      0.05). Mean (SD) inspiratory work of breathing decreased from 1.77 (0.70) J. min
      1 to 0.31 (0.36) J.min-1 at 5 cmH2O and 0.16 (0.26) J.min-1 at 10 cmH2O pressure
      support ventilation (n = 9, p < 0.05). Analysis of the respiratory rhythm in the
      second group of seven patients revealed an oscillating respiratory pattern in
      four patients at 5 cmH2O and six of the seven patients at 10 cmH2O pressure
      support ventilation. The metabolic advantage of the decreased work of breathing
      during pressure support ventilation during anaesthesia is unlikely to balance the
      disadvantage of an oscillating respiratory rhythm.

PMID- 8546281
TI  - External high frequency oscillation in normal subjects and in patients with acute
      respiratory failure.
AB  - External high frequency oscillation was performed on 20 healthy volunteers using
      a cuirass-based system, the Hayek Oscillator. Five-min periods of oscillation
      were carried out on each subject at frequencies of 1, 2, 3, 4 and 5 Hz. Effective
      ventilation was measured in terms of the fall in alveolar partial pressure of
      carbon dioxide immediately after oscillation. The optimum frequency for
      oscillation was 1-3 Hz but most of the subjects were adequately ventilated over a
      wide range of frequencies. Thus, the Hayek Oscillator is capable of adequately
      ventilating normal subjects by means of chest wall oscillation. We also compared
      external high frequency oscillation with intermittent positive pressure
      ventilation in five patients with respiratory failure. Using the same inspired
      oxygen fraction, the external high frequency oscillation replaced intermittent
      positive pressure ventilation for a 30-min period. External high frequency
      oscillation improved oxygenation by 16% and reduced the arterial carbon dioxide
      by 6%. These preliminary findings suggest that normal subjects and intensive care
      unit patients can be adequately ventilated by means of external high frequency
      oscillation.

PMID- 8546283
TI  - Cerebral oximetry: a useful monitor during carotid artery surgery.
AB  - Cerebral oximetry was evaluated as a monitor of oxygenation during carotid
      endarterectomy in 22 patients. The oximeter was a reliable continuous monitor,
      identifying changes in cerebral oxygenation during episodes of hypotension and
      after arterial occlusion. Changes in oxygenation correlated well with the
      surgical assessment of backbleeding after arterial clamping, but less well with
      other methods which are used to make a decision on insertion of an arterial
      shunt. There was no correlation between internal carotid artery stump pressure
      and change in cerebral oxygenation after application of the arterial cross clamp.
      However, cerebral oxygenation correlated weakly with the change in middle
      cerebral artery velocity as measured by transcranial Doppler ultrasonography (r =
      0.49, p < 0.02).

PMID- 8546282
TI  - Anaesthesia and adverse effects after intrathecal pethidine hydrochloride for
      urological surgery.
AB  - Anaesthesia, postoperative analgesia and the incidence of adverse effects after
      intrathecal pethidine hydrochloride 0.50 mg.kg-1 and 0.75 mg.kg-1 were assessed
      and compared with a conventional technique using isobaric bupivacaine 13.75 mg in
      patients undergoing transurethral resection of the prostate gland. Sensory and
      motor block were significantly shorter with both pethidine regimens than with
      bupivacaine (p < 0.001). Although sensory and motor block were shorter after
      pethidine 0.50 mg.kg-1 than after pethidine 0.75 mg.kg-1 the difference in
      duration was clinically insignificant. The incidence of incomplete motor block
      was significantly greater with pethidine 0.50 mg.kg-1 than with bupivacaine 13.75
      mg.kg-1 (p < 0.01). Visual analogue pain scores recorded after the operation were
      low and were similar in the pethidine groups to those obtained with bupivacaine
      alone. Mean arterial blood pressure was significantly lower in both pethidine
      groups compared with the bupivacaine group between 30 and 240 min after
      intrathecal injection (p < 0.001). However, the within-group reductions in blood
      pressure were within clinically acceptable limits. The incidences of nausea and
      emesis were low and emesis occurred in patients in the bupivacaine group only (p
      < 0.03). Pruritus was seen only in patients receiving pethidine. Intra-operative
      sedation occurred more often in patients receiving both pethidine 0.50 mg.kg-1
      and 0.75 mg.kg-1 compared with patients receiving bupivacaine (p < 0.04). Both
      pethidine regimens provided acceptable anaesthesia and there were no significant
      differences between the two regimens in quality of intra-operative anaesthesia,
      incidence of adverse events or postoperative analgesia.

PMID- 8546284
TI  - The neuromuscular blocking effects of vecuronium during sevoflurane, halothane
      and balanced anaesthesia in children.
AB  - Forty-five children aged 5-12 years were randomly allocated to receive 1.0 MAC of
      sevoflurane or halothane, or balanced anaesthesia with propofol and alfentanil.
      The ulnar nerve was stimulated every 20 s supramaximally with a train-of-four
      pattern and adductor pollicis electromyography was recorded. A cumulative log
      probit dose-response curve of vecuronium was established. Thereafter, spontaneous
      recovery of neuromuscular function was monitored until complete. Effective doses
      of vecuronium were lowest in the sevoflurane group and greatest during balanced
      anaesthesia; for 50% neuromuscular blockade these were 13.3% micrograms.kg-1,
      21.8 micrograms.kg-1 and 36.6 micrograms.kg-1 during sevoflurane, halothane and
      balanced anaesthesia, respectively, p < 0.05. Recovery of neuromuscular function
      was slower during sevoflurane than during halothane or balanced anaesthesia.
      Sevoflurane potentiated vecuronium more than halothane; when compared to balanced
      anaesthesia the dose requirements of vecuronium were reduced by approximately 60%
      and 40%, respectively.

PMID- 8546285
TI  - Evaluation of a new method for determining tracheal tube length in children.
AB  - Most paediatric tracheal tubes are marked in centimetres from the tip. In 105
      children, nasotracheal tube length was set at the level of the vocal cords such
      that all 3.0 and 3.5 mm internal diameter tubes were placed with the 3 cm mark at
      the cords, all 4.0 and 4.5 tubes were set at 4 cm at the cords and all 5.0 and
      5.5 tubes were set at 5 cm at the cords. Subsequent chest X ray showed that 79%
      of the tracheal tubes were in the ideal midtracheal position, one tube was
      marginally short and 20% of the tubes were marginally long. Neither bronchial
      intubation nor accidental extubation occurred in any subject. This is an
      effective method to determine tracheal tube length which may be used for both
      oral and nasal intubation.

PMID- 8546286
TI  - Gastric regurgitation during general anaesthesia in different positions with the
      laryngeal mask airway.
AB  - Ninety patients, divided into three groups of 30, were investigated to determine
      the incidence of gastric regurgitation during general anaesthesia administered
      via the laryngeal mask airway in the supine, Trendelenburg and lithotomy
      positions. Fifteen minutes before induction of anaesthesia each patient swallowed
      a 75 mg methylene blue capsule. At the end of surgery, the LMA and the oropharynx
      were inspected for bluish discoloration which was considered to be a sign of
      gastric regurgitation. No blue dye was detected in the supine group but it was
      observed in one patient in each of the other two groups.

PMID- 8546287
TI  - The influence of anaesthetic technique upon the immune response to hysterectomy.
      A comparison of propofol infusion and isoflurane.
AB  - Earlier studies on propofol have shown increased percentages of T helper cells
      after minor surgery. In this study, the effects of propofol infusion anaesthesia
      on the immune response were compared with those of combined isoflurane
      anaesthesia in 30 patients (median age 47 years, ASA 1-2) undergoing major
      surgery. The total dose of propofol in the propofol infusion group of 15 women
      was 860 mg (range 540-1520 mg) and the median end-expiratory isoflurane
      concentration in the combined isoflurane group of 15 women was 0.6% (range 0.5
      0.8). The following were measured; leucocyte and differential counts; percentages
      of lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16 and HLA-DR+CD3);
      phytohaemagglutinin-, concanavalin A-, and pokeweed mitogen-induced and
      unstimulated lymphocyte proliferation; plasma interleukin-6; serum group II
      phospholipase A2, C-reactive protein and cortisol concentrations. Measurements
      were made pre-operatively, at the end of the operation and on the first and fifth
      postoperative days. No statistically significant overall differences were
      observed in the immune response between the groups. The serum cortisol response
      was weaker in the propofol group than in the isoflurane group (p < 0.05). Time
      related changes were seen within the groups.

PMID- 8546288
TI  - SCOTI--a new device for identification of tracheal intubation.
AB  - A new lightweight device for the detection of placement of a tracheal tube in the
      trachea or oesophagus is described. The device utilises a sonic technique
      detecting resonating frequencies in an open (trachea) or closed (oesophagus)
      structure. Evaluation of the device in a clinical environment is described and it
      has been shown to be capable of verifying the correct placement of the tracheal
      tube in the trachea in 98% of patients studied. Further evaluation of this
      intubating aid appears justified.

PMID- 8546289
TI  - Resistance, reverse flow and opening pressure of unidirectional valves.
AB  - Based on a new preliminary standard of the 'Comite Europeen de Normalisation',
      the following unidirectional valves were tested with regard to resistance,
      opening pressure, reverse flow and dislocation: the Drager inspiratory and
      expiratory valves, the Engstrom inspiratory valve, the Ohmeda valve, the Siemens
      Ventilator 710 inspiratory and expiratory valves, the Siemens Ventilator 900C
      unidirectional valve of the absorber and the Megamed 700 inspiratory and
      expiratory valves of the circle system 219 (Megamed 700 CS 219). The following
      valves fulfilled all Comite Europeen de Normalisation requirements: Drager
      inspiratory and expiratory valves, Siemens 900 absorber valve and Megamed 700 CS
      219 inspiratory valve. The Siemens 710 valve and the Megamed 700 CS 219
      expiratory valve did not meet the requirements for flow resistance. The Ohmeda
      and Siemens 710 valves and the Engstrom inspiratory valve did not fulfil the
      Comite Europeen de Normalisation requirements for reverse flow. In addition, the
      Engstrom inspiratory valve did not comply with the dislocation test. The
      requirements for the opening pressure were met by all the valves tested. Valves
      with the disc in a horizontal position achieved better results than those with
      the disc in a vertical position. These measurements, showing the differences in
      the performance of various types of valves confirm the feasibility of the
      standards proposal.

PMID- 8546290
TI  - Percutaneous catheterisation of the internal jugular vein. 1969.

PMID- 8546291
TI  - Relief of tension subcutaneous emphysema using a large bore subcutaneous drain.
AB  - We report a case of subcutaneous emphysema following multiple attempts to
      cannulate both subclavian veins for pacemaker insertion. Initial bilateral
      pneumothoraces were complicated by subcutaneous emphysema which became so severe
      that respiration and cardiac output became seriously impaired. The insertion of a
      single large bore subcutaneous drain produced a dramatic improvement. The
      aetiology, complications and management of tension subcutaneous emphysema are
      discussed.

PMID- 8546292
TI  - The accuracy of references in Anaesthesia.
AB  - We reviewed all the references quoted in Volume 45 (1990) (n = 3967) and half the
      references quoted in Volume 49 (1994) (n = 2183) of Anaesthesia. The references
      were numbered sequentially and 100 references from each year were randomly
      selected. Citations of non-journal articles were omitted leaving 197 citations
      for careful scrutiny. The authors' names, article title, journal title, volume
      number, page numbers, and year were examined in each selected reference. A
      reference was deemed correct if each element of the citation was identical to its
      source. Of the references examined, 32% and 41% contained one or more errors in
      1990 and 1994, respectively. The elements most likely to be inaccurate were, in
      descending order of frequency, article title, author, and page number. There was
      no significant difference in the error rate between the 2 years. It is the
      responsibility of contributors to ensure that all references are carefully
      checked.

PMID- 8546293
TI  - Postoperative emesis following otoplasty in children.
AB  - Sixty unpremedicated children aged between 3 and 14 years, scheduled for
      otoplasty, were randomly divided into one of three groups to receive either
      ondansetron 0.1 mg.kg-1, droperidol 75 micrograms.kg-1, or placebo at induction
      of anaesthesia. All patients received a standard general anaesthetic using
      thiopentone, atracurium and halothane. Opioid analgesia was avoided intra
      operatively and infiltration with local anaesthetic was used prior to the start
      of surgery. Children who received ondansetron were less likely to vomit (15%)
      than those who received either droperidol (40%) or placebo (60%) (p < 0.01). This
      group also tolerated oral ingestion of fluids and solids earlier than those who
      received either droperidol or placebo (p < 0.001). There was no difference
      between the placebo or droperidol group in the incidence of vomiting or time to
      ingestion of oral fluids and meals. Three patients in the ondansetron group had a
      self-terminating nodal rhythm which was not associated with any haemodynamic
      disturbances. Postoperatively there were no untoward incidents in any of the
      groups and all patients were discharged home the day after surgery.

PMID- 8546294
TI  - Comparison of ondansetron and droperidol in reducing postoperative nausea and
      vomiting associated with patient-controlled analgesia.
AB  - In a randomised, placebo-controlled trial we have compared the efficacy of
      ondansetron and droperidol in reducing postoperative nausea and vomiting
      associated with patient-controlled analgesia after orthopaedic surgery. One
      hundred and forty five patients, ASA 1 and 2, undergoing major orthopaedic
      surgery were anaesthetised using a standardised technique. They were randomly
      allocated to receive patient-controlled analgesia as morphine 1 mg.ml-1 alone;
      morphine as before plus a single dose of 1.25 mg droperidol together with 0.083
      mg.ml-1 in the infusion syringe; or morphine as before plus 4 mg ondansetron and
      0.13 mg.ml-1 in the syringe. The patient-controlled analgesia bolus dose was set
      at 1 ml with a 5 min lockout and a 4 h maximum dose of 30 mg morphine. There was
      no background infusion. The occurrence of nausea, vomiting and sedation was
      assessed every 4 h. The incidence of vomiting decreased from 59% in the morphine
      only group to 35% and 14% in the droperidol (p < 0.05) and ondansetron groups (p
      < 0.001) respectively. The number of patients suffering from nausea alone was not
      significantly different between the three groups, although those in the
      ondansetron group experienced less severe nausea (p < 0.05) when using a two
      point scale. The droperidol group had significantly higher sedation scores than
      the other two groups (p < 0.005). We conclude that ondansetron is superior to
      droperidol when used with patient-controlled analgesia and causes less sedation.

PMID- 8546295
TI  - Reading in the operating theatre.

PMID- 8546296
TI  - Demand for high dependency units.

PMID- 8546297
TI  - Where's the evidence? The Cochrane Collaboration and anaesthesia.

PMID- 8546298
TI  - Excessive noise caused by a jet ventilator.

PMID- 8546299
TI  - Noise and anaesthetic gas pollution.

PMID- 8546300
TI  - Screen or sound? Aids for blind intubation.

PMID- 8546301
TI  - Resuscitation skills of trainee anaesthetists.

PMID- 8546302
TI  - Resuscitation skills of trainee anaesthetists.

PMID- 8546303
TI  - Should we keep the anaesthetic room?

PMID- 8546304
TI  - Clinical characteristics of commonly used spinal needles.

PMID- 8546305
TI  - Another site for the pulse oximeter probe.

PMID- 8546306
TI  - Anaesthesia and Robinow syndrome.

PMID- 8546307
TI  - Long-term tracheal intubation in burn patients.

PMID- 8546308
TI  - Hypothesis: halothane hepatitis--has thymol been overlooked?

PMID- 8546309
TI  - Cardiomyoplasty and muscle relaxants.

PMID- 8546310
TI  - Pneumothorax and laparoscopic fundoplication.

PMID- 8546311
TI  - Ketanserin and urapidil during myocardial revascularisation.

PMID- 8546312
TI  - Medical scientific writing.

PMID- 8546313
TI  - Cardiac tamponade--a potentially fatal complication of central venous
      catheterisation.

PMID- 8546314
TI  - Serum triglyceride levels and propofol infusion.

PMID- 8546315
TI  - Influence of nitrous oxide on propofol dosage and recovery after intravenous
      anaesthesia.

PMID- 8546316
TI  - Are pencil point needles the answer for peripheral neural blockade?

PMID- 8546317
TI  - Intra-operative tracheal obstruction by tumour fragments.

PMID- 8546318
TI  - Spinal anaesthesia in acute colonic pseudo-obstruction.

PMID- 8546319
TI  - A morphological study of cultured endodermal cells of chick embryo:
      characteristics of adhesion, spreading and locomotion.
AB  - A study is made of the morphological characteristics of the endodermic cells of
      the stage 5 chick embryo by means of in vitro cell culture techniques. The
      scanning electron microscope revealed that the endodermic cells in cultures were
      rounded, tended to be smooth and had few blebs and microvilli. Regarding cell
      projections typical of culture cells, such as filopodia, lamellipodia and
      pseudopodia, there was a noteworthy scarcity after 12 h growth, although greater
      cellular activity was observed at 24 h, characterized by the presence of
      filopodia and an ability of the cells to form clusters on the substratum. These
      facts show the morphological and adhesion movements of the endodermal cells
      studied to be related mainly with the presence of filopodia as the most abundant
      cell projections.

PMID- 8546320
TI  - Renal venous architectonics in domestic swine.
AB  - Renal venous architectonics were investigated in 240 kidneys from 120 swines at
      an age of 1-8 months. The methods used were: preparation, corrosion and X-ray
      examination. It was established that, in 75% of the cases, v. renalis cranialis
      and v. renalis caudalis were present. In the rest of the cases (25%), v. renalis
      intermedia was present. It was also observed that right and left renal veins
      formed distentions, which enveloped the caudal medial part of each adrenal gland.
      V. adrenalis (suprarenalis) was not formed as an independent blood vessel. Venous
      blood from the adrenal gland drains through 2-3 orifices in these distentions.
      This study describes vv. prelobares, vv, interlobares and vv. arcuatae.
      Anastomoses were found between them. On that basis this concluded that the renal
      venous system in domestic swine is not segmented.

PMID- 8546321
TI  - Morphological studies of the valves of the kidney vein in domestic swine.
AB  - It was established macroscopically that 37.5% of the renal veins investigated
      possess valves. Valves were observed on both sides, but predominantly on the left
      side of the kidneys (14.58%). Some valves were also observed in the main branches
      of the renal veins. The structure of the valves was studied with the use of light
      and electron microscopy. The most important finding was the observation of mast
      cells in the valves. This is probably a common biological phenomenon, since mast
      cells have been observed in the cardiac valves and the wall of the renal artery
      and vein.

PMID- 8546322
TI  - Ultrastructure of the carotid body of the goat.
AB  - The carotid body of the goat was found to be a small oval or rounded
      parenchymatous organ. It was characterized by its profound vascularity. Delicate
      septa divided the parenchyma into small feebly defined lobules. Electron
      microscopy revealed that the parenchyma comprised type I cells, type II cells,
      nerve endings, axons and fenestrated dilated capillaries. Type I cells were
      characterized with electron dense-cored vesicles. They showed variations in size
      and concentration of the dense-cored vesicles and number of mitochondria. The
      possibility that these variations are reflections of different stages of activity
      is discussed. Type II cells were less numerous than type I cells, relatively
      small and devoid of dense-cored vesicles. They usually surrounded small groups of
      type I cells and associated nerve endings and axons. Presumptive afferent nerve
      endings characterized with many clear vesicles, occasional large granular
      vesicles and varying numbers of slender mitochondria, lay apposed to type I
      cells. Nerve endings of this kind showed afferent and efferent synaptic junctions
      with type I cells. Presumptive sympathetic efferent endings were occasionally
      seen within the lobules but never lay apposed to type I cells or afferent nerve
      ending.

PMID- 8546323
TI  - An SEM study of the morphology of the lower respiratory-tract surface of the
      reindeer (Rangifer tarandus tarandus L.).
AB  - The morphological features of the surface of the lower respiratory tract
      (trachea, bronchus, bronchiolus, distal airways, and alveoli) from 10 reindeer
      (Rangifer tarandus tarandus L.), differing in age and sex, were studied using
      scanning-electron microscopy. The respiratory surface of the reindeer generally
      resembles that reported previously in similar studies for other mammalian
      species. Ciliated epithelial cells, goblet cells, microvillous cells, Clara
      cells, alveolar epithelial cells of type 1 and type 2, and alveolar macrophages
      could be distinguished by their universally characteristic surface morphologies.
      The rarity of Kohn pores in the alveolar walls of reindeer was considered to be
      the most striking difference in comparison to most other species.

PMID- 8546324
TI  - The endocrine cells in the gastro-enteric tract of adult fallow deer (Dama dama
      L.).
AB  - Endocrine cells were detected in the gastro-enteric tract of the fallow deer by
      means of immunohistochemical procedures, using antibodies against serotonin,
      somatostatin, gastrin, glucagon and cholecystokinin. The number of cells positive
      for each antiserum in each region was evaluated. Serotonin-containing
      enterochromaffin (Ec) cells were present in every region investigated and were
      most numerous in the proximal duodenum. Cells positive for somatostatin were
      present in all the regions studied, with the exception of the colon, and were
      especially numerous in the proper gastric-gland region. Cells that were stained
      by the anti-gastrin antibody were very numerous in the pyloric-gland region but
      only rare in the duodenum. Glucagon-immunoreactive cells were only detected in
      the large intestine and their frequency was always less than 10/0.5 mm2.
      Cholecystokinin-containing cells were scarce and restricted to the pyloric-gland
      region and duodenum.

PMID- 8546325
TI  - [Fine structure of the trigeminal nerve nucleus of the domestic fowl].
AB  - The trigeminal nerve nuclei are examined light- and electron-microscopically in
      the adult domestic fowl. The nucleus sensibilis principalis nervi trigemini is
      formed by scarce, medium-sized, round-to-ovoid polygonal neurons. The Nissl
      bodies are concentrated around the nucleus and consist of short cisterns of the
      rough endoplasmic reticulum densely bordered with ribosomes. The nucleus tractus
      spinalis nervi trigemini extends to the first segments of the cervical cord. The
      rostral part of the nucleus is characterized by medium-sized polygonal neurons.
      Their cell bodies are densely packed with coarse Nissl bodies. Small multiforme
      cell types with large nuclei frequently showing two nucleoli predominate in the
      caudal part. The motorical main portion, nucleus motorius nervi trigemini
      consists of medium-sized as well as great polygonal neurons. The accessory
      portion, nucleus motorius dorsalis nervi trigemini, consists of medium-sized
      polygonal neurons. Both nuclei show the typical motoneuron cytomorphology. In the
      neuropil, the axodendritic synapses can be differentiated into five types.
      Occasionally, densely packed glial lamellae and giant mitochondria occur.

PMID- 8546326
TI  - Study of ACTH-immunoreactive cells after transplantation of neonatal adrenal
      glands into adult adrenalectomized rats.
AB  - The morphological and morphometrical features of the ACTH-immunoreactive cells of
      the anterior pituitary gland were compared between adult rats with intact
      adrenals, adult rats without adrenals, and adult rats with regenerated
      adrenocortical nodules. The removal of the adrenal glands produced a great
      increase in the number and size of the cytoplasmic processes of the ACTH
      immunoreactive cells that sometimes establish contact with those of the
      neighbouring immunoreactive cells. In addition, in this experimental group, the
      ACTH-cell percentage and the mean cell, cytoplasmic, and nuclear areas were
      greatly increased in comparison with those found in control animals. Several
      regenerated adrenocortical nodules were observed in the small-bowel segment of
      rats transplanted with neonatal adrenal glands. The percentage and morphometrical
      values of the pituitary ACTH-reactive cells of this experimental group, although
      slightly increased relative to the rats with intact adrenals, were greatly
      decreased in relation to those of the adrenalectomized animals. It is concluded
      that the neonatal adrenal tissue regenerated after its transplantation into adult
      rats, a process that modified the percentage, the morphological characteristics,
      and the morphometrical values of the ACTH-immunoreactive cells of the
      adrenalectomized rats.

PMID- 8546327
TI  - Ultrastructural study of the early development of the sheep embryo.
AB  - An ultrastructural study of the different stages of pre-implantation in sheep was
      carried out, analysing the changes brought about mainly in the morula and
      blastocyst stages. The analysis of the embryos obtained showed a series of common
      characteristics in all stages, most noticeable being the presence of a high
      number of vesicles distributed in a uniform way in the cytoplasm, and also the
      presence of numerous electron-dense mitochondria in many varied forms. The most
      important ultrastructural modifications took place at the 16-cell stage and
      affected, principally, the nucleus, which presented numerous condensations of
      chromatin distributed along the nucleoplasm. The nucleoli adopted a reticular
      morphology, abandoning the compact aspects presented in the previous stage. These
      changes might be involved in the synthesis of embryonic RNA, and, accordingly, in
      the activation of the genome of this species. These data indicate that this stage
      is critical to the embryonic development and might be related to the blockage
      produced in the development of cultivated sheep embryos at the point of
      transition from 8 to 16 cells. Nevertheless, it should be pointed out that the
      first signs of modifications in the aspect of the nucleus are observed at the
      four-cell stage, being characterized by the appearance of vacuolated areas in the
      nucleolus, indicating the first signs of embryonic nucleic activity, which would
      anticipate the main change in the control of the protein synthesis.

PMID- 8546328
TI  - Descriptive and comparative myology of the hindlimb of the babirusa (Babyrousa
      babyrussa L. 1758).
AB  - A description is given of the anatomy of the muscles of the hindlimb of the
      babirusa (Babyrousa babyrussa L. 1758). Four adult animals, two males and two
      females were dissected and the results compared with previously published
      information. Significant differences were found between the accounts and these
      were analysed within the contexts of material availability and advances in
      anatomical nomenclature. Comparisons made with published descriptions of the pig
      (Sus scrofa) showed that the muscular anatomies of the two species are very
      similar. Those differences which are apparent, despite intraspecies variation in
      structure, include a thoracic vertebral origin for the M. psoas minor in babirusa
      but not pig, a smaller gluteal tongue to the M. gluteus medius in the babirusa, a
      failure of the Mm. gluteus medius to meet on the dorsal midline in the babirusa
      unlike the case in the pig, the two heads of the M. gluteus accessorius are of
      unequal size in the babirusa but not in the pig, the vertebral head of the M.
      obturatorius externus is absent in the babirusa and present in the pig.

PMID- 8546329
TI  - Histomorphologic and histochemical characteristics of carpal glands (Glandulae
      carpeae) in domestic swine (Sus scrofa domesticus) and wild swine (Sus scrofa
      ferus).
AB  - Investigations were carried out on samples from carpal glands of domestic and
      wild swine of different ages. The anatomic position of carpal glands is identical
      in domestic and wild swine. Glandular acini in domestic swine are bigger and more
      scarce than in wild swine. LDH activity is more intense in wild swine, while the
      activity of the investigated diaphorases is almost even. The activity alkaline
      and acid phosphatase is stronger in domestic swine, while the activity of non
      specific esterases is present only in wild animals. The more or less manifest
      presence of all investigated enzymes indicates that carpal glands in domestic and
      wild porcine specimens are very active metabolically. Regarding the intensity of
      enzymatic reactions, some differences are probably due to different sexual
      maturity, as well as to the method of feeding and housing in these groups of
      animals.

PMID- 8546331
TI  - Expression of connexin 32 gap junction protein in the kidneys during fetal
      development of the hamster (Mesocricetus auratus).
AB  - The expression of gap junction protein was examined immunohistochemically using
      affinity-purified antibody against rat liver gap junction protein, connexin 32
      (Cx32), in the kidneys of fetal (gestation days 13-16) and adult Syrian golden
      hamsters. Phalloidin histochemical staining, PNA- and RCA I-lectin staining, NCAM
      immunostaining, and alkaline phosphatase and Na(+)-K(+)-ATPase enzyme
      histochemical staining were performed in combination with Cx32 immunostaining.
      The kidney sections were observed with a confocal scanning laser microscope. By
      gestation day 13, Cx32 immunoreactivity was observed in the differentiating
      tubules. The Cx32 staining was localized on the lateral cell membrane of the
      cells lining the developing proximal tubules, while the S-shaped bodies,
      developing distal tubules, and collecting tubules showed no positive
      immunostaining. As the kidney developed, the density of Cx32 immunoreactivity
      increased. As the gap junction provides pathways for cell-cell communication, the
      development of Cx32 expression may imply that this structure plays an important
      role in renal tubule development. Confocal scanning laser microscopy provided a
      clear image of the fluorescence-labeled cell structures, free from out-of-focus
      blur. Using the same sections, stereoscopic images were easily reconstructed from
      serial optical sections, and were helpful in understanding the spatial
      distribution of Cx32 expression in the developing fetal proximal tubules.

PMID- 8546330
TI  - Structure and function of podocytes: an update.
AB  - Glomerular visceral epithelial cells, also termed podocytes, are highly
      specialized epithelial cells that cover the outer aspect of the glomerular
      basement membrane. Recent studies point to an important role of podocytes in the
      physiology and pathophysiology of the glomerulus. This review summarizes the
      structure-function relationships of podocytes. Following a description of the
      general morphology of podocytes, the technical problems associated with studying
      these cells are discussed. A survey of podocyte function forms the center of this
      review. Finally, selected aspects of podocyte development and cell division are
      discussed.

PMID- 8546332
TI  - Postnatal maturation of tissue kallikrein-producing cells (connecting tubule
      cells) in the rat kidney: a morphometric and immunohistochemical study.
AB  - The mature, fully differentiated connecting tubule (CNT) cell plays an important
      role in the regulation of serum potassium levels and synthesizes the enzyme
      tissue kallikrein, a main component of a renal vasoactive system, the kallikrein
      kinin system. To characterize the growth of CNT cells (tissue kallikrein
      producing cells), we studied the rat kidney at three different time points of
      postnatal development: at day 5, day 15, and day 30. The CNT cells were
      identified on tissue sections by a standardized immunohistochemical procedure.
      The tissue kallikrein content was determined by radioimmunoassay and the activity
      of the enzyme in kidney homogenates was measured using a selective synthetic
      substrate. The number of immunolabeled CNT and CNT cells per cortex area
      gradually increased from day 5 to day 30. A similar rise in the content and
      activity of tissue kallikrein was observed when the enzyme levels were determined
      by radioimmunoassay or by the enzymatic method. In addition, the morphometric
      analysis showed that the distal end of CNT had larger cells that displayed a more
      intense tissue kallikrein staining than those present in the proximal end,
      suggesting that the postnatal development of CNT is induced from its
      juxtamedullary portion. Our results show that tissue kallikrein expression is
      very low in the newborn rat, increasing gradually with age to reach adult levels
      at day 30. This finding, together with the morphometric data, suggests immaturity
      of CNT cells in newborn rats, a fact that could contribute to explaining the high
      serum potassium levels reported at this stage. In addition, the contrasting
      behavior of kallikrein and renin in the postnatal development (kallikrein
      increasing and renin decreasing) could explain the gradual decrease in renal
      vascular resistance and increase in renal blood flow observed after birth.

PMID- 8546333
TI  - Coculture of the vomeronasal organ and olfactory bulb of the fetal rat.
AB  - The vomeronasal organ and the olfactory bulb of the rat were cocultured from 15
      day embryo siblings on collagen-coated membrane in Dulbecco's modified Eagle's
      medium containing fetal calf serum, horse serum, and antibiotics. At 4 days in
      vitro (DIV), vomeronasal axons forming two to three large fascicles were seen
      originating from the explants of the vomeronasal organ. Differential axonal
      growth was observed. Some fascicles made connections with the explants of the
      olfactory bulb. Twenty percent of the cocultures studied here showed the
      formation of connections. At 6-10 DIV many fascicles that did not connect with
      the olfactory bulb had degenerated, and large fascicles that were connected with
      the olfactory bulb survived for more than 10 DIV. The formation of connections
      between the vomeronasal organ and the olfactory bulb in coculture favors the
      survival of large nerve fascicles, but it could not be determined whether or not
      the presence of the olfactory bulb affects the initial orientation of the fibers
      and fascicles from the explants of the vomeronasal organ.

PMID- 8546334
TI  - Potential intraembryonic hemogenic sites at pre-liver stages in the mouse.
AB  - In the course of a previous experimental study on the early development of the
      mouse embryo hemopoietic system, we found that, at the 10-25 pairs of somite
      stages, the para-aortic splanchnopleure contains hemopoietic progenitors. Trying
      to discover a structural basis for this potentiality, we have looked for
      cytological signs of hemopoiesis in the embryo proper between 8.5 and 12 days
      post-coitum, i.e. prior to full-blown fetal liver hemopoiesis. Two suggestive
      findings are reported: (1) intra-arterial hemopoietic cells aggregates are
      present in the omphalomesenteric and umbilical arteries and to a lesser degree in
      the dorsal aorta; (2) cells groups resembling yolk sac blood islands are observed
      in the mesentery. The intra-arterial aggregates are strikingly similar to the
      intra-aortic clusters of avian embryos. These cytological aspects provide the
      anatomical basis underlying recent functional data that revealed the hemogenic
      capacity of the para-aortic splanchnopleure.

PMID- 8546335
TI  - The thickness of the subchondral plate and its correlation with the thickness of
      the uncalcified articular cartilage in the human patella.
AB  - The regional thickness distributions of the subchondral plate and the
      unmineralized part of the articular cartilage were morphometrically determined in
      normal human patellae, and the correlation coefficient for each specimen
      calculated from the paired measurements. For this purpose the patellae were
      embedded in methyl methacrylate and cut as serial sections, which were assessed
      with a Vidas image-analyzing system (Kontron). The values obtained were used to
      reconstruct the individual and average thickness distributions and to calculate
      the correlation coefficients for each subject. Both the thickness of the
      subchondral plate and that of the cartilage revealed regular distributions which,
      however, followed different patterns. Central regions with maximum values from
      which the thickness decreased concentrically towards the periphery were found in
      both. However, the distribution patterns of the unmineralized cartilage and the
      subchondral plate could be clearly distinguished, both by the position of the
      maxima and by the arrangement of the isocrassids (contour lines of equal
      thickness). The thicknesses of the two tissues showed a correlation between 0.38
      and 0.82 (mean 0.6). We attribute this to their different reactions to the type
      of stress acting upon them. It appears that the thickness of the subchondral
      plate is principally determined by stresses acting over a longer period of time
      with low frequency, whereas the thickness of the articular cartilage seems to be
      a response to intermittent dynamic stresses of a higher frequency.

PMID- 8546336
TI  - Morphological analysis of the role of the neural tube and notochord in the
      development of somites.
AB  - The differentiation of avian somites and skeletal muscles, which themselves are
      derived from somites, was studied in ovo after the isolation of the unsegmented
      segmental plate from the notochord and/or neural tube by surgical operations at
      the level of the segmental plate. In each experiment, the newly formed somites
      had a normal histological structure, with an outer epithelial somite and core
      cells in the somitocoeles. Thereafter, the three derivatives of the somites
      (dermatome, myotome and sclerotome) reacted differently to the different
      operations. When the somites developed without the notochord, only somitocoele
      cells showed massive cell death, and muscles developed regardless of the presence
      or absence of the neural tube. On the contrary, no cell death was observed in any
      part of the somites that were formed with the neural tube or the notochord
      present, and muscle cells developed. However, in those embryos that retained only
      the notochord, striated muscles developed only in the lateral body wall. In each
      of the experimental operations, the surface ectoderm always covered the somites,
      and, regardless of the state of sclerotome and/or myotome differentiation, the
      dermatome always survived. These histological observations indicate that the
      first step in somite formation is independent of axial structures. The results
      further suggest that the notochord may produce diffusible factors that are
      necessary for the survival and further development of sclerotomal cells, and that
      both the neural tube and notochord can support muscle differentiation. However,
      it is likely that each structure has a relationship to the development of epaxial
      muscles and hypaxial muscles respectively. Furthermore, an intimate relationship
      may also exist between the surface ectoderm and the development of the dermatome.

PMID- 8546337
TI  - Regeneration following somite removal in chick embryos.
AB  - A technique was developed for ensuring complete removal of single somites with
      minimal damage to surrounding tissues in 2-day-old chick embryos. Histological
      examination of the site of somite removal at various time intervals after
      operation revealed that a regeneration mechanism could be triggered. Replacement
      of the cells that had been removed could occur, but the extent of the replacement
      was dependent on the immediate fate of the gap created. If the gap was closed by
      enlargement of the adjacent somites, no replacement of the cells occurred. If the
      gap remained, then cells invaded the gap and were able to produce a normal
      sclerotome and dermomyotome. By labelling adjacent cells with the carbocyanine
      dye. DiI, it was shown that the replacement cells could come from the adjacent
      somites, as well as the intermediate mesoderm. Use of an antibody to HNK-1
      established that the replacement cells did not come from the neural crest and
      that the neural crest cell distribution was little affected. Staining with peanut
      agglutinin showed that the replacement cells were able to adopt the
      characteristics associated with rostral and caudal halves of the normal
      sclerotome. These results provide possible explanations for the variety of
      vertebral anomalies produced by removal of somites and for the production of some
      congenital vertebral anomalies.

PMID- 8546338
TI  - The adrenergic innervation of the rat central amygdaloid nucleus: a light and
      electron microscopic immunocytochemical study using phenylethanolamine N
      methyltransferase as a marker.
AB  - Using immunocytochemistry of phenylethanolamine N-methyltransferase for light and
      electron microscopy, investigations were carried out to document the morphology
      of adrenergic afferents innervating the rat central amygdaloid nucleus and to
      analyse the manner in which contacts with neurons of the nucleus are formed. With
      the light microscope, dense terminal plexus of phenylethanolamine N
      methyltransferase-immunoreactive axons with typical large boutons (diameter > 1
      micron) were found in the medial central nucleus, extending into its ventral
      subdivision and the adjacent intra-amygdaloid portion of the bed nucleus of the
      stria terminalis. Electron microscopy of the medial central nucleus showed
      phenylethanolamine N-methyltransferase-immunoreaction product in the cytoplasm of
      intervaricose axons and boutons. Large adrenergic boutons contained numerous
      small clear vesicles and, occasionally, large dense-cored vesicles. In serial
      sections, most boutons formed synaptic contacts. Synapses of immunoreactive
      terminals were mainly of the asymmetric type and localized preferentially on
      medium sized to small dendrites and dendritic spines. Structures postsynaptic to
      adrenergic boutons were often additionally contacted by non-labelled terminals.
      The study gives evidence that adrenergic afferents exert a direct synaptic
      influence on medial central nucleus neurons. The peripheral localization of the
      majority of adrenergic synapses, their asymmetric configuration, and the presence
      of non-adrenergic synapsing terminals in their immediate vicinity indicate that
      the major component of the adrenergic input is of an excitatory nature, and is
      integrated with innervation from other sources.

PMID- 8546339
TI  - Failure to detect free radicals in the isolated perfused rat heart.
AB  - Oxygen free radicals have been indirectly implicated in reperfusion injury
      following ischemia in the isolated rabbit heart. The authors moved to detect free
      radicals in an isolated rat heart model as a prerequisite to studying its effects
      during ischemia and reperfusion. Several different spin trapping agents and
      electron paramagnetic resonance (EPR) spectroscopy were used to detect free
      radicals being generated during ischemia and reperfusion. The possible roles of
      ferrous iron and hydrogen peroxide generation in reperfusion injury were also
      investigated. No free radical "bursts" were detected with any of the spin traps
      used in this model during ischemia or reperfusion. Hydrogen peroxide and hydroxyl
      free radicals do not appear to be involved in tissue reperfusion injury. This
      study suggests that free radicals are not produced in clinically significant
      quantities under these conditions to account for ischemic myocardial damage.

PMID- 8546340
TI  - Aortic coarctation with two intercostal aneurysms, appearing radiographically as
      a subclavian aneurysm. A case report.
AB  - The authors present a case of adult aortic coarctation with two associated
      intercostal aneurysms and poor left ventricular function. The intercostal
      aneurysms appear, radiographically, as a subclavian aneurysm. The case
      illustrates, in aortic coarctation, the potential difficulty in defining the
      anatomy of the associated vascular aneurysms. The authors also demonstrate that
      the left ventricular function markedly improves after resection of the aortic
      coarctation.

PMID- 8546341
TI  - Power spectral analysis of heart rate in elderly hypertensive subjects with or
      without silent coronary disease.
AB  - Much evidence indicates an involvement of the sympathetic nervous system in the
      genesis of silent myocardial ischemia. The authors assessed autonomic system
      activity by power spectrum analysis of heart rate variability in 21 elderly
      hypertensive men with and without angiographically confirmed coronary artery
      disease and compared the results with those from an age-matched control group. In
      the analysis an autoregressive algorithm was used to determine the power spectrum
      from an electrocardiographic recording of 512 consecutive RR intervals. The
      autonomic nervous system induces two distinct sinusoids: a low-frequency signal
      attributable to sympathetic activity and a high-frequency vagal response. In the
      hypertensive patients with coronary disease the authors also evaluated
      sympathetic activation after double-blind, placebo-controlled administration of
      metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20
      mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day).

PMID- 8546342
TI  - Clinical science review: current aspects of thrombolytic therapy in women with
      acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) remains the greatest threat to health in our
      society and is the most common cause of death in the United States and in many
      other Western industrialized countries. Recent data demonstrate that mortality
      from MI is continuing to decline. In these days of more aggressive management of
      acute MI (AMI) there has been a resurgence of interest in advances in
      thrombolytic therapy. However, observational studies of patients with AMI have
      shown that women sustaining an AMI have a worse prognosis than men. AMI is the
      number-one killer of women in the United States; approximately 247,000 of more
      than 520,000 deaths due to AMI that occur each year are among women, and almost
      one-third of the women are younger than forty-five years old. While there have
      been great advances in thrombolytic therapy, these advances have benefited men to
      a more significant degree than they have benefited women. The purpose of this
      paper is to critically review the efficacy of thrombolytic therapy in women with
      AMI with consideration of some of the key components of its effectiveness:
      mortality, bleeding risk, infarct-artery patency, ventricular function, and
      cardiac arrhythmia.

PMID- 8546343
TI  - Alteration of left ventricular filling evaluated by Doppler echocardiography as a
      potential marker of acute rejection in orthotopic heart transplant.
AB  - To evaluate the changes in left ventricular (LV) filling associated with acute
      cardiac rejection, serial Doppler echocardiographic (ED) examination were
      performed on the same day as endomyocardial biopsy (EMB) in 40 patients who
      underwent orthotopic transplantation. The diameters and wall thickness of the
      left ventricle were measured. The indexes of LV filling in the following
      parameters were measured by pulsed Doppler: isovolumic relaxation time (IRT),
      peak early mitral flow velocity (V max E), and pressure half-time (PHT). The
      patients were classified into three groups on the basis of EMB: Group I (19
      patients without rejection), Group II (11 patients with mild or moderate
      rejection), and Group III (10 patients with severe rejection). In Group III
      rejection was associated with a significant increase of posterior wall thickness
      (P < 0.05), with a decrease of IRT (P < 0.05), and an increase of V max E
      velocity (P < 0.01) in comparison with Group I. In Group II, Doppler indexes were
      not statistically significant in comparison with Groups I and II. In conclusion,
      in transplant patients, a diagnosis of acute rejection can be suspected in severe
      rejection by use of echocardiography when the diagnosis is based on a
      multiparametric evaluation of different ED indexes (m-mode and Doppler indexes).
      Doppler echocardiography is a method with an excellent specificity but
      insufficient sensitivity; this is due to the influence of recipient atrial
      contraction timing on Doppler indexes of LV filling.

PMID- 8546344
TI  - Changing prevalence of coronary heart disease risk factors and cardiovascular
      diseases in men of a rural area of Crete from 1960 to 1991.
AB  - This study compares the prevalence of coronary heart disease (CHD), risk factors
      (RF), and cardiovascular diseases (CVD) among Cretan men from a rural area
      examined in 1960 and 1991. The study population consisted of 148 men in 1960 and
      42 men in 1991 of the same age group (fifty-five to fifty-nine years old) and
      from the same rural area. All men had a complete examination of the
      cardiovascular system and a resting electrocardiogram (ECG). Systolic BP (SBP) >
      or = 140 mmHg was found in 42.6% of the subjects in 1960 and in 45.2% in 1991
      (NS). Diastolic BP > or = 95 mmHG was found in 14.9% of the subjects in 1960 as
      opposed to 33.3% in 1991 (P < 0.02). Total serum cholesterol (TSCH) > or = 260
      mg/dL approximately 6.7 mmol/L) was found in 12.8% of the subjects in 1960 and in
      28.6% in 1991 (P < 0.01). Heavy smokers ( > or = 20 cigarettes/daily) were 27.0%
      in 1960 as compared with 35.7% in 1991 (:NS); 5.4% of the subjects in 1960 had
      light physical activity (PA) as compared with 14.3% in 1991 (P < 0.01); 74.7% of
      the subjects were farmers in 1960 as compared with 43.6% in 1991 (P < 0.1). The
      prevalence of CHD was 0.7% in 1960 as compared with 9.5% in 1991 (P < 0.001).
      Hypertensive heart disease was found in 3.4% of the subjects in 1960 and 4.8% in
      1991 (NS). The prevalence of all major CVD was much higher in 1991 (19.1%) as
      compared with 1960 (8.8%) (P < 0.01). In conclusion, the prevalence of CHD RF and
      CVD was much higher in 1991 than in 1960 for Cretan men of the same age group.
      This higher prevalence seems to be related to dietary and life-style changes that
      have taken place in Crete during the last thirty years.

PMID- 8546345
TI  - Cerebrovascular hemodynamic inefficiency of premature ventricular contractions.
AB  - Transcranial Doppler (TCD) measurements of middle cerebral artery (MCA) blood
      flow velocities were recorded and synchronized with electrocardiographic (EKG)
      recordings in 52 EKG/TCD complexes in 4 patients. Thirty-seven normal sinus beats
      and 13 conductive and 2 nonconductive premature ventricular contractions (PVCs)
      were examined. Mean velocities averaged 45 +/- 4 cm/sec for normal sinus rhythm
      (NSR) vs 26 +/- 4 cm/sec in the PVC group (P = 0.007). Peak systolic velocities
      averaged 74 +/- 6 cm/sec for the NSR and 45 +/- 7 cm/sec in the PVC group (P =
      0.016). The latency between the QRS complexes and corresponding TCD wave forms
      (QRS-SU) averaged 0.12 +/- 0.03 sec in NSR AND 0.17 +/- 0.04 sec for the PVC
      group (P < 0.001). In addition, QRS-SU was inversely related to all velocities.
      PVCs appeared to be less hemodynamically efficient than NSR. The lower blood flow
      velocities and increased QRS-SU may result from lower stroke volume and delayed
      ventricular contraction associated with the aberrant QRS complex.

PMID- 8546346
TI  - Inoue balloon pericardiotomy for patients with recurrent pericardial effusion.
AB  - The results and follow-up data for 11 patients with recurrent effusion due to
      various etiologies who underwent balloon pericardiotomy with the Inoue balloon
      catheter between May 1992 and July 1994 are described. Inoue balloon
      pericardiotomy was successful in 10 patients (91%), who remained free of
      pericardial effusion at a mean follow-up duration of 4.2 months. All patients
      tolerated the procedure well with minimal discomfort and with no complications.
      Despite good symptomatic relief, 9 patients (82%) eventually succumbed to disease
      dissemination, with a mean survival time of 1.4 months. It is concluded that
      Inoue balloon pericardiotomy is a safe and useful alternative to surgical
      pericardial windowing for the symptomatic treatment of recurrent pericardial
      effusion.

PMID- 8546347
TI  - Intimal medial thickening of common carotid artery as indicator of coronary
      artery disease.
AB  - The authors investigated the relation between coronary atherosclerosis,
      angiographically detected, and intimal-medial (I-M) thickening of the common
      carotid artery (CCA), as measured by high-resolution B-mode ultrasound system.
      They studied 31 patients with coronary artery disease (CAD) and 23 healthy
      control subjects. I-M thickening of CCAs and atheromatous plaques at the carotid
      bifurcation were evaluated. A score system was defined (range 0-20) based on the
      absence or presence of atherosclerotic lesions at common and internal carotid
      arteries. A coronary angiography score was defined based on the presence of of
      atherosclerotic lesions at nine coronary arterial segments (range 0-36). The
      thickness of CCAs (M +/- SD) in CAD patients was significantly higher (1.45 +/-
      0.95 mm) than in controls (0.87 +/- 0.10 mm, P < 0.005), and an I-M thickening of
      1.1 mm or more was specific and positively predictive of CAD. A significant
      positive correlation between coronary and carotid score was observed (P < 0.028,
      r = 0.373). The study suggests that I-M thickening could be helpful for the
      identification of patients at risk for CAD.

PMID- 8546348
TI  - Isolated corrected transposition of great arteries and double left anterior
      descending artery originating from the left and right coronary artery. A rate
      combination of coronary artery anomaly and congenital heart disease.
AB  - A case of double left anterior descending coronary artery in a patient with
      isolated corrected transposition of great arteries is presented. The double
      artery originated from the left main stem and the right coronary artery. There
      were no stenoses on these two arteries. This anomaly seems to be very rare.

PMID- 8546349
TI  - Stroke--a rare presentation of Eales' disease. A case report.
AB  - Eales' disease is common in India and the Middle East, but its neurologic
      manifestations are rare. The authors report a young man with recurrent vitreous
      hemorrhage and acute amnestic confusional state who subsequently developed
      myelopathy. Eales' disease should be considered in the differential diagnosis of
      stroke in a young patient.

PMID- 8546350
TI  - Percutaneous transluminal coronary angioplasty of anomalous coronary arteries.
      Case reports.
AB  - To date, technical experience reported in the literature is very limited on
      angioplasty in patients with anomalous coronary arteries. Balloon angioplasty may
      be a more favorable approach for revascularization in these vessels. A major
      factor is selection of the guiding catheter. The authors report 4 patients with
      severe atherosclerotic lesions of anomalous coronary arteries who underwent
      coronary angioplasty of the anomalous vessel. Three patients had an anomalous
      circumflex artery and 1 had an anomalous right coronary artery. Angiographic and
      clinical success were achieved in 3 patients.

PMID- 8546351
TI  - The postmyocardial infarction syndrome--vanished or vanquished? A twenty-five
      year follow-up. A case report.
AB  - Although the existence of the postmyocardial infarction syndrome has now long
      been questioned, the Dressler symptom complex remains widely accepted as a
      distinct clinical entity. A patient is described whose twenty-five-year follow-up
      adds to our argument that there is no late or separate multisystem autoimmune
      disease following acute myocardial infarction. It is suggested that the Dressler
      complex is an entity that has neither vanished nor been vanquished but one that
      may never have existed.

PMID- 8546352
TI  - Idiopathic dilatation of the pulmonary artery. A case presentation.
AB  - Idiopathic dilatation of the pulmonary artery is an uncommon, but not rare,
      congenital anomaly that is diagnosed by exclusion and generally has a benign
      clinical course. A left hilar mass on the chest x-ray film is the major
      presentation. The authors present a case of idiopathic dilatation of the
      pulmonary artery with posttraumatic chest pain clinically. After serial
      examinations, idiopathic dilatation of the pulmonary artery was diagnosed. They
      discuss the phenomenon of transpulmonary valvular pressure gradient and
      noninvasive tools for long-term follow-up, including transesophageal
      echocardiography and magnetic resonance imaging.

PMID- 8546353
TI  - Synergistic inhibitory effect of angiotensin-converting enzyme inhibitor and
      heparin on intimal hyperplasia after rat aorta injury.
AB  - The respective efficacies of angiotensin-converting enzyme (ACE) inhibitor and
      standard heparin were investigated with respect to their inhibitory effects on
      intimal hyperplasia after balloon denudation of rat aorta. Local angiotensin II
      effects in the artery wall may participate in regulation of the vascular response
      to arterial injury, apparently independent of the plasma renin and angiotensin
      system. ACE inhibitors have been shown to block intimal hyperplasia after
      arterial injury in rats. Increasing evidence points toward an inhibitory effect
      of heparin on intimal hyperplasia independent of anticoagulation. Balloon
      catheter aortic denudation was performed in 25 rats pharmacologically treated
      from six days or one day before to fourteen days after surgery and split into
      four groups: group A (control group), normal feeding; group B (ramipril group),
      ramipril 10 mg/kg/day orally; group C (heparin group), heparin 1200 IU/kg/day
      subcutaneously; group D (combined group), both ramipril and heparin. Animals were
      killed and aortas were perfused and fixed at physiologic pressure fourteen days
      after denudation. Cross-sectional intima-to-media area ratios (I-M ratio) were
      calculated by an image analyze system.

PMID- 8546354
TI  - Budd-Chiari syndrome as a complication of Behcet's syndrome. A case report.
AB  - Budd-Chiari syndrome (BCS) is a very infrequent complication of Behcet's
      syndrome. The authors report a young, male patient with Behcet's syndrome
      presenting with BCS. He underwent emergency surgery for thrombectomy but
      unfortunately died during the operation.

PMID- 8546355
TI  - Buerger's disease in a middle-aged woman with diabetes mellitus. A case report.
AB  - Buerger's disease or thromboangiitis obliterans with involvement of small
      arteries of the upper and lower extremities usually afflicts young male smokers,
      but this report presents a middle-age female nonsmoker with diabetes mellitus who
      satisfied clinical, angiographic and histologic criteria for the diagnosis of
      Buerger's disease.

PMID- 8546356
TI  - Quality assurance in clinical chemistry and haematology.

PMID- 8546357
TI  - The measurements and testing programme of the European Union in the field of
      biomedical analysis: reference materials and cooperation between European EQAS.
AB  - Abut twenty years ago, the European Commission established the BCR (Bureau
      Communautaire de Reference) programme with the objective of improving the quality
      of the results of measurements, in order to assist in the establishment of
      reliable and comparable measurement systems in the EU member states. Its usual
      procedure consists of collaborative studies--involving preferably laboratories
      from all member states--in terms of: intercomparisons, research and development
      and preparation and certification of reference materials when necessary. The aim
      of the biomedical activities of the programme is to harmonize results obtained
      from analyses of samples of tissues and biological fluids. In the current
      programme "measurements and testing" (BCR's successor) emphasis is focused on two
      categories of activities: 1) feasibility preparation and certification of
      reference materials (including the appropriate method development when necessary)
      and 2) collaboration between EU national external quality assessment schemes
      (EQA).

PMID- 8546358
TI  - European legislation of biomedical technology.
AB  - The primary objectives which the European directive proposal wants to reach are:
      a) to guarantee a high quality standard of the products which are put into the EC
      market, for the user; b) to guarantee the safety and health of the user and of
      all other people who come into direct contact with the said products. The
      directives define a precise scheme of regulation and control for all medical
      devices and this scheme is in force for all the member states of European Union.

PMID- 8546359
TI  - Organization and results of a pilot scheme for external quality assessment in
      clinical chemistry carried out in the Latium region, Italy.
AB  - The results of an external quality assessment scheme (EQAS), carried out in the
      Latium region between October 1987 and December 1988, are reported. Ninety-four
      laboratories, both public and private, took part in the scheme. Aim of the scheme
      was to estimate the reliability of the clinical chemistry services in this
      region. The participating laboratories received eight control samples for EQA,
      every two months. The analytes to be determined in each sample were: glucose
      (GLU), urea (UR), total protein (TP), uric acid (UA), creatinine (CR), bilirubin
      (BIL), cholesterol (CHO), triglycerides (TRI), sodium (Na), potassium (K),
      calcium (Ca), aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      creatine kinase (CPK), gamma glutamyl transferase (GGT), and alkaline phosphatase
      (ALP). Global laboratory performances were evaluated in terms of interlaboratory
      precision, accuracy--as deviation per cent from the target values and coefficient
      of variation (CV)--and percentage of results within pre-set acceptability limits.
      The deviations were reasonably low, whereas the CVs were rather high. The
      percentage of acceptable results was lower than 50% for the analytes urea,
      calcium, uric acid, creatine kinase and alkaline phosphatase. The performance of
      the examined laboratories was worse than those obtained in other regional and
      national EQAS, both in terms of CVs and percentage of acceptable results.

PMID- 8546360
TI  - Italian external quality assessment scheme in immunoassay.
AB  - This paper deals with the organization, the data processing and some of the
      results obtained in Italian external quality assessment (EQA) schemes for
      hormones, tumor markers and hepatitis B markers. The EQA for hormones and tumor
      markers includes up to sixteen analytes together with the participation, in 1990,
      of about 250 laboratories. Laboratory results were used to prepare periodic and
      end-of-period reports. The former includes the results (with the related
      statistical parameters) obtained by all participants and by laboratories using
      the same method, as well as the histogram of the data. The end-of-period report
      contains estimates of imprecision and average bias for all laboratories, for each
      laboratory and for the more widely employed kits. From 1980 to 1988, laboratory
      variability improved significantly for TSH, progesterone, estradiol,
      testosterone, CEA and ferritin, slightly for cortisol, FSH, prolactin and AFP,
      while there was no improvement for both total T3 and T4. For LH we found an
      unusually high variability mainly due to systematic differences between kits
      based on different monoclonal antibodies. About 200 laboratories participated in
      the EQA for hepatitis B markers (HBsAg and anti-HBs) organized in 1990. For these
      analytes the periodic reports show the percentage of negative and positive
      results and the histogram of the responses (absorbance or counts) normalized with
      respect to the cut off.

PMID- 8546361
TI  - A pilot programme of external quality assessment for general haematology in
      Italy.
AB  - In the years 1984-1989 the Istituto Superiore di Sanita organized an EQAS for
      haematology (SVEQE) in Italy. A series of trials for haemocytometry, abnormal
      haemoglobins, HbA2, HbF, red cell G6PD and peripheral blood films, were carried
      out with the participation of 126 hospital laboratories, in different regions.
      SVEQE was an educative programme, aiming at promotion of quality assurance (QA)
      in laboratory haematology. At the same time an attempt was made to survey the
      analytical methods and instruments and to estimate the "state of the art" by the
      dispersion of all results. Participant laboratories were not scored for their
      performances. The operative protocol was harmonized to the guidelines established
      by WHO and ICSH; the trial specimens were prepared from normal or pathologic
      blood samples provided by blood banks or hospital departments. The trials for
      haemocytometry demonstrated a wide use of completely automated analyzers and in a
      steady state of performance during about five years. CVs, mainly for WBV and PLT,
      were somewhat higher than in other countries, where national QA systems have been
      established for a long time. Such discrepancies were not surprising in a pilot
      programme and were likely to be caused by inadequate internal quality control.
      The exercises for abnormal haemoglobins, HbA2, HbF and G6PD pointed out the need
      of using standardized methods according to the recommendations of ICSH. A large
      number of participating laboratories took part in the trial for blood cell
      morphology, being convinced of the educative function of this exercise; it is
      important to continue with systematic surveys, even including rare haematological
      disorders amongst the selected cases.

PMID- 8546362
TI  - Quality assurance in the determination of metals in clinical chemistry and
      toxicology: the METOS project. Metalli Tossici.
AB  - National external quality assessment schemes (EQAS) for the determination of
      trace elements in blood (Al, Cd, Cu, Pb, Zn) have been promoted in Italy since
      1983. They were organized by a working group of the Istituto Superiore di Sanita
      and known as "METOS (Metalli Tossici, toxic metals) project". The organization of
      the schemes included the preparation of suitable control materials by the
      promoting centre and the elaboration of valuable strategies of sample
      distribution, treatment of data and evaluation of results, that could be applied
      even to a small number of participants. The procedures used and the results
      obtained in ten years of activity of the METOS project are reported. Within the
      framework of the programme some information has been obtained, confirming the
      validity of the procedures used for sample preparation, sample distribution and
      evaluation of laboratories performance.

PMID- 8546363
TI  - National and regional regulations on minimal requirements, quality control and
      accreditation for clinical laboratories in Italy.
AB  - The national law concerning minimal requirements and quality control for clinical
      laboratories, dating back to 1984, is a decree of the President of the Council of
      Ministries (DPCM). Minimal requirements are established regarding general
      organization of the laboratory, instrumental equipment's, the personnel, the list
      of analytical tests, the director of the laboratory and its responsibilities, and
      quality control systems. Concerning regional legislation, since 1978 eighteen
      regions and the two autonomous provinces of Trento and Bolzano have issued--in
      the matter of minimal requirements and quality control for clinical laboratories,
      and point of specimen collection--laws, decrees, resolutions, deliberations,
      regulations and circulars that have determined in Italy a disparity of situations
      and a non-homogeneous regulation. The prerogative of the regions has been
      recently confirmed (laws 502/1992 and 517/1993): the introduction of appropriate
      procedure for the accreditation of both public and private services who want to
      operate within the National Health Service is defined as impelling. The
      homologation to operate may be acquired if the structure or the service actually
      has the instrumental, technical, and professional endowment corresponding to
      criteria established on a national basis. The national legislator deemed it
      necessary to establish a coordination on a national basis to uniform and
      standardize protocols, operating procedures, and methods of evaluations. The
      Istituto Superiore di Sanita (ISS) can have a key role in this coordination
      activity, mainly concerning technical/scientific aspects.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8546364
TI  - The role of standardization in quality assurance.
AB  - The main organizations involved in standardization of laboratory medicine are
      described. At the international level these are mainly: ISO, IEC, WHO, ICSH, IFCC
      and COWS/WASP, while at the European level CEN, CENELEC and BCR are involved in
      standardization activities in Europe. At the present the European Commission is
      preparing a directive on in vitro diagnostic. This document will rely, for its
      implementation, on standards prepared by CEN/CENELEC.

PMID- 8546365
TI  - External quality assessment programs in Lombardy, Italy.
AB  - In Italy, although a national decree (DPCM of 10/2/84) established that quality
      control programs involving clinical laboratories should be carried out on a
      regional basis, external quality assessment schemes (EQAS) are actually run only
      in some regions. Among these is Lombardy, where an EQAS in clinical chemistry
      concerning 20 analytes was set up in 1986, and where at present EQA programs (for
      clinical chemistry, haematology and coagulation) compulsory for both private and
      public laboratories, are under way. This was made possible by both regional laws
      and the constant care shown by the regional Committee on pathology department
      system (Comitato Regionale per l'Ordinamento dei Servizi di Patologia, CROSP).
      The participation in the schemes (including control material supply) is free of
      charge. The identity of participants is known only to officers in charge of
      quality control and analytical results are therefore managed anonymously.
      Consequently EQAS carried out in Lombardy are not exacting or punitive. In the
      EQAS for clinical chemistry the following analytes are considered: glucose, urea,
      proteins, albumin, chloride, sodium, potassium, total calcium, inorganic
      phosphate, iron, urate, creatinine, cholesterol, triglycerides, aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine
      phosphokinase, gamma glutamyl transferase and alkaline phosphatase. In the EQAS
      for haematology and coagulation the tests are: a) leukocytes, erythrocytes,
      haemoglobin, haematocrit, mean cell (erythrocyte) volume, platelets; b)
      prothrombin time, activated partial thromboplastin time, fibrinogen and
      antithrombin III. The general organization of the schemes, the statistical
      procedures adopted for the analysis of data, and some of the results obtained in
      the three EQA programs are reported in detail in the present article.

PMID- 8546366
TI  - Organization and results of the Veneto region (Italy) external quality assessment
      program for clinical chemistry.
AB  - The Veneto region EQA program has been developed on the basis of the law that
      created the national health service and then on the regional social-health plans.
      Organizer and reference laboratory is the Biomedical Research Center in
      Castelfranco Veneto (TV). The aim of the program is to describe the state of the
      art in the public and private laboratories, and to evaluate the performances of
      each laboratory according to the schemes recommended by the European Committee
      for Clinical Laboratory Standards (ECCLS). Even though the program was not
      obligatory, participation has always been about 80% for public laboratories and
      increased from 70% to almost 100% in the private ones. The results showed very
      good interlaboratory agreement for electrolytes; iron assay has improved in the
      last two years; there have been standardization problems for urea and creatinine;
      among enzymes, the results are good for GGT and ALT, but not satisfactory for AST
      and more so for ALP. Since 1990, accuracy evaluation for 9 constituents has been
      introduced. The results are good for electrolytes and organic constituents but
      standardization problems are shown for enzyme methods, especially with ALP and
      AST.

PMID- 8546367
TI  - External quality assessment scheme in Tuscany, Italy.
AB  - According to the Regional Law n. 44 of 6/6/1988, all public and private
      laboratories in Tuscany, Italy, are obligated to carry out internal quality
      control and participate in external quality assessment programmes. The external
      quality assessment schemes are directly managed by "Regione Toscana" by means of
      the "Centro regionale di riferimento per la sicurezza di qualita". The programme
      for clinical chemistry (comprising cholesterol, glucose, urea, creatinine,
      sodium, potassium, calcium, uric acid, total proteins, ALT, AST, GGT) started in
      1990 by sending two lyophilized serum samples from eight pools, each containing a
      different analyte concentration. In 1992 the analytes were increased to eighteen,
      chloride, phosphate, bilirubin, triglycerides, iron and alkaline phosphatase
      being added. At the same time the first cycle of the EQAs dedicated to the blood
      coagulation (including PT, APTT and fibrinogen) was started. In every cycle each
      laboratory must perform 16 analyses, by testing 8 pairs of samples from 8
      different pools. The samples from different pools are sent by separate dispatches
      and in random order. Thus the participating laboratories receive and analyze the
      samples in a different sequence.

PMID- 8546368
TI  - Piedmont region (Italy): setting quality standards and testing.
AB  - In this report we describe the two years (1991-1992) EQA programmes organized by
      the health committee of the Piedmont region (Italy). This programme was mandatory
      for all public and private laboratories. The parameters analysed were: PT and
      APTT (for coagulation); Hb, RBC, WBC, platelets and MCV (for haematology);
      glucose, urea, creatinine, total proteins, cholesterol, uric acid, triglycerides,
      AST, ALT, LDH, GGT, amylase, alkaline phosphatase, sodium, potassium, calcium,
      chloride, phosphorus and iron (for clinical chemistry). For haematology, the
      comparison between the first and the second year shows a significant decrease of
      imprecision, especially for platelets, WBC and MCV.

PMID- 8546369
TI  - Quality of clinical information: a new approach of EQA in Emilia-Romagna, Italy.
AB  - For correct enforcement of an external quality assessment (EQA) scheme, suitable
      parameters are required for the assessment of analytical performance. Traditional
      EQA schemes have always been chiefly concerned with the agreement of analytical
      results between laboratories. Although we consider this concept to be important,
      we also believe that particular attention must be paid to the quality of the
      clinical information, in relation to correct use of the results. On the basis of
      this principle, we have developed an EQA model which, besides considering the
      absolute value, also take the reference limits (RLs) into consideration by means
      of the normalization procedure. The evaluation of clinical information is of
      vital importance, especially in relation to immunoassays, since the low degree of
      standardization between methods, and the ensuing phenomenon of relative
      inaccuracy, make the use of suitable RLs essential. Actually, analysis of the
      results reveals a high degree of heterogeneity in the RLs used by the
      laboratories, even within the same method-groups.

PMID- 8546370
TI  - Quality assurance programs in the United States.
AB  - The College of American Pathologists (CAP) provides quality assurance programs
      for clinical laboratories, including surveys for external quality assessment,
      quality assurance service for internal and regional quality control, and Q-probes
      for overall quality assurance including pre- and post-analytic factors. These are
      complemented by inspections through the laboratory accreditation program and a
      standards program linked with the national reference system for clinical
      chemistry. Expert resource committees, organized according to scientific
      disciplines, provide professional support and direction for these programs.
      Numerous other professional societies jointly sponsor various surveys, which
      optimize available expertise, size, and quality of these programs. CAP surveys
      are the most widely used programs for proficiency testing (PT) in the United
      States. PT programs only partially characterize performance. Clinical
      laboratories are best evaluated by a combination of measures, including EQA,
      internal and regional quality control, monitors of pre- and post-analytic
      quality, and inspection.

PMID- 8546371
TI  - EQA pilot regional program for haematology in Emilia-Romagna, Italy.
AB  - A pilot regional EQA scheme in haematology has been implemented in Emilia
      Romagna. The distinctive features of this scheme are: a) inter-laboratory
      comparability of results on a local basis has been selected as main target of the
      whole scheme; b) fresh blood has been chosen as ideal control material; c) a fast
      and effective dispatching system of control material has been accomplished. This
      has been made possible by means of the hospital ambulances network and an express
      delivery service; d) the assessment of the analyzers calibration alignment in the
      whole region has been subdivided in two phases. The first one consists in
      aligning all analyzers of each province with the corresponding reference
      provincial center, the second one in aligning the analyzers of the eight
      reference centers in the region with each other; e) all laboratories taking part
      in the EQA scheme have been directly involved. Preparation of control material
      and comment sheet mailing to participants are carried out by eight provincial
      reference centers. Initial setting of the scheme targets, collegial survey of
      results and alteration of the scheme guidelines involve all participants in the
      scheme; f) a distinction between a short-term and a medium-term goal has been
      made. The short-term one is to improve the harmonization of results for
      comparability between different laboratories in the same area. The medium-term
      one is to set up educational programmes and consensus procedures for establishing
      operative protocols and for defining the allowable analytical errors, set on the
      basis of clinical requirements.

PMID- 8546372
TI  - The quality assurance system in clinical chemistry.
AB  - The quality assurance system in clinical chemistry allows for the identification
      of errors and control actions to correct them. It is well known that laboratory
      errors can be classified as: pre-analytical, analytical and post-analytical.
      While pre-analytical and post-analytical errors are very difficult to identify,
      the analytical variability (both imprecision and inaccuracy) can be monitored
      with internal quality control (IQC) programs and external quality assessment
      (EQA) schemes. The purpose of IQC is mainly to verify the stability of laboratory
      estimates with time and therefore it is essentially a control of imprecision. IQC
      programs are based on the use of control samples which are analyzed in each
      analytical series. The easiest method of representing IQC data is by the use of
      Shewhart's chart, although "cusum" chart and Youden plot are often useful. As for
      the criteria according to which an analytical series should be accepted or
      rejected, the use of practical control rules is widely spread in laboratories.
      Participation in EQA schemes allows the laboratory to have a retrospective
      estimate of its performance in terms of both imprecision and inaccuracy, if
      definitive or reference methods are available. In lack of definitive or reference
      methods, consensus mean or median can be derived from the data obtained by all
      the participants or, in some cases, by the participants using the same analytical
      method (e.g. for analytes not yet completely characterized and measured with
      immunoassays.

PMID- 8546373
TI  - Quality assurance programmes in Portugal in the fields of clinical chemistry and
      haematology.
AB  - Quality assurance programmes in Portugal in the fields of clinical chemistry and
      haematology are running on under the organization of the correspondent
      laboratories of the National Institute of Health. They are carried out with
      voluntary participation for public and private clinical laboratories with
      confidentiality of results. The design comprehends two parts, each one
      supplementing the other: internal quality control, external quality assessment
      being the motivation for quality assurance usually done through courses and
      laboratory activities organized even before the laboratories enter the external
      scheme. In clinical chemistry: with six trials a year and 23 parameters to be
      analysed, the target values are assigned by reference laboratories. The survey
      reports involve a personal message and an Youden plot being the assessment of
      performance done either by a deviation index (DI) or, on enzymes, by a consensus
      value established among the participants. Yearly an individual message is
      produced to report the evolution of laboratory results. The state of the art
      shows a good performance of reference laboratories. The participant laboratories
      still evidence some difficulties on enzymes, bilirubin, creatinine, urates and
      urea determinations. In haematology the target value is the consensus median
      value of participant laboratories using the same kind of equipment, semi and
      totally automated. As survey reports two kinds of computer forms are produced: an
      individual message where each laboratory results are compared with the others
      through a DI, an yearly message with the DI evolution. Up to this date ten
      surveys a year are carried on for general haematology.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8546374
TI  - Quality assurance in Belgium.
AB  - Clinical laboratories in Belgium working within the social security system
      require to be licensed. Internal quality control and participation in external
      quality assessment (EQA) belong to the licensing conditions. The evolution of the
      Belgian EQAs is outlined, including a performance evolution over the last ten
      years. Halving of interlaboratory CVs is observed for most clinical chemistry and
      immunoassay analytes. Improvement is less spectacular for haematological analytes
      and is missing for coagulation analytes. Using the results of EQAs 1989-1991 the
      mean overall method interlaboratory CVs could be estimated. Using data from a
      commercial internal quality control program for clinical chemistry and a request
      in 145 laboratories, current intralaboratory CVs are estimated.

PMID- 8546375
TI  - Quality assurance programmes in the United Kingdom.
AB  - Quality assurance in laboratory medicine includes: a) constant checking of test
      reliability by internal quality control (IQC), b) external quality assessment
      (EQA) by an independent agency to check performance of a number of laboratories
      at intervals in order to obtain a retrospective indication of their performance,
      and c) proficiency control by supervision of pre-test and post-test phases of
      laboratory work, from specimen collection to delivery of report to the clinician.
      In the UK the majority of laboratories are aware of the importance of IQC and to
      a greater or lesser extent they all perform some IQC procedures. These are
      briefly described, with special reference to the special requirements of
      haematology. A description is also given of the organizational structure of the
      EQA scheme which was established in the UK at a national level (UK NEQAS). This
      has an important role in ensuring good laboratory practice in both the national
      health service and the private sector.

PMID- 8546376
TI  - External quality assessment schemes for clinical chemistry in the United Kingdom.
AB  - The system of UK national external quality assessment schemes (NEQASs) has been
      developed over more than 20 years, using logical criteria for scheme design and
      operation, and their usefulness is supported by evidence of continuing improved
      performance. The UK approach has built on the enthusiasm and knowledge of
      individual experts working to provide a fully integrated system of EQASs to
      facilitate the provision of reliable patient care.

PMID- 8546377
TI  - EQA for general haematology in the United Kingdom.
AB  - In the United Kingdom the national quality assessment scheme (NEQAS) in
      haematology organizes regular surveys for blood counts, blood films, reticulocyte
      counts, cytochemistry, identification of abnormal haemoglobins, HbA2 and HbF
      quantitation, G6PD screening tests, assays of serum vitamin B12, folate and
      ferritin. For most tests there has been significant reduction in inter-laboratory
      variance despite occasional blunders. This illustrates the role of NEQAS in
      improving the standard of laboratory practice in the UK. The problems in equating
      analysis of NEQAS survey materials with routine laboratory specimen are
      discussed.

PMID- 8546378
TI  - External quality assessment schemes for clinical chemistry in Germany.
AB  - The external quality assessment schemes in clinical chemistry are regulated by
      the guidelines of the Federal Association of Physicians for Quality Assurance in
      Medical Laboratories (Richtlinien der Bundesarztekammer zur Qualitatssicherung in
      Medizinischen Laboratorien) which are part of a legal act. The basis of the
      mandatory quality assessment in medical laboratories is the internal accuracy and
      precision control. The target values for the internal accuracy and external
      quality control are determined by method-independent reference methods as far as
      possible. But for most of the analytes method-dependent assigned values are
      determined by expert laboratories. The decision limits for the internal and
      external quality control are derived from the interindividual dispersions of the
      analytes of a normal population (reference intervals) and should meet the medical
      requirements. The advantages of method-independent target values are discussed.

PMID- 8546379
TI  - External quality assessment scheme for haematology in Germany.
AB  - Quality control in haematology is performed in Germany for 20 years. Both cell
      count, haemoglobin measurement and differential count on smear with morphology
      exercise and probably diagnosis will be demanded by the participants. Until now
      this quality control is not mandatory, even efforts are done to change this
      circumstance, given by the main input of diagnostic value due to haematology
      results. So this regulation will be changed very soon, in order to submit
      haematological laboratories to governmental control, effected by the BAK
      (Bundesarztekammer), as already is done in clinical chemistry. For this EQA the
      participants cannot expected any financial support by any organization, nor
      public health, nor private assurance. The role of referee laboratories and
      reference values as well as difficulties for the adequate reference material are
      discussed. For the differential count other limits have to be established:
      recognition of pathological blood films is one of the most important point (in
      sense of morphological exercise) to ensure broad knowledge of "flag
      interpretation". Since the last year quality control for reticulocyte count and
      flow cytometry for immune status and leukemia-differentiation has been
      established.

PMID- 8546380
TI  - Relevance of analytical and biological variations to quality and interpretation
      of test results: examples of application to haematology.
AB  - In the frame of a comprehensive quality system, the level of quality to be
      attained (analytical goals or quality specifications) need to be defined. Among
      the several approaches used for such a definition, that based on the (intra
      individual) biological variation seems to be scientifically sound, and the most
      universally applicable. Data on biological variation are easily generated by
      applying specific experimental protocols. Once the biological variation is known,
      it can be combined to the analytical variation for the calculation of the
      critical difference. This is the difference between two repeated measurements in
      the same patient, due to the effect of both analytical and biological variation:
      when this difference is exceeded, a significant change in the patient's condition
      can be assumed. Some examples of calculation of the analytical goals and of the
      critical differences are shown, based on some quantities usually measured in the
      haematological laboratory.

PMID- 8546381
TI  - Characteristics and performance of the external quality assessment scheme (EQAS)
      for haematology in Spain. Ten years of experience.
AB  - The external quality assessment scheme for haematology (EQAS-H) in Spain started
      in 1984 with 56 laboratories, being 473 in 1994. Participants come from public
      health services (70%) and from private laboratories (30%). Surveys are performed
      monthly or quarterly depending on the tests and on each occasion the following
      samples are prepared and sent by the professional organizing team: human
      (HIV/HBsAg free) or equine whole blood for cell counts (erythrocytes and
      leucocyte), platelet suspensions for platelet counts, lyophilized plasmas for
      prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen (F) and
      antithrombin III (ATIII), and blood films for cell morphology and reticulocyte
      counts. In 1992 a new scheme on oral anticoagulant treatment control (OATC) has
      been established jointly by the Spanish Haematology Association (AEHH) and the
      Spanish Society of Thrombosis and Haemostasis (SETH). After preparation, the
      control material is sent to participants in the scheme where the requested tests
      are performed and the results reported back to the organizer (Haematology
      Laboratory Department of Hospital Clinic i Provincial) for statistical analysis.
      For evaluating the results, laboratories are divided into four to eight groups
      depending on the methodologies used. Individual results are assessed against a
      consensus value (mean) and a deviation index (DI) from the mean, and the
      coefficient of variation (CV), Youden plots and other statistical information are
      provided for all results and groups of each parameter. More than 80% of
      laboratories responded regularly (up to 6 trials) for blood counts and
      haemoglobin and compared to the previous year (1984), the values of CV(%)
      improved significantly for RBC count (from 3.3 to 2.2%), haemoglobin (from 2.7 to
      2.1%) and platelet count (from 22.6 to 16.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8546382
TI  - DNA vectors. Precedents and safety.

PMID- 8546383
TI  - Retroviral vectors for HIV immunotherapy.

PMID- 8546384
TI  - Immunization against viral proteins with naked DNA.

PMID- 8546386
TI  - Risk potential of the chromosomal insertion of foreign DNA.

PMID- 8546385
TI  - Improved cationic lipid formulations for in vivo gene therapy.
AB  - The problem of assessing in vivo activity of gene delivery systems is complex.
      The reporter gene must be carefully chosen depending on the application. Plasmids
      with strong promoters, enhancers and other elements that optimize transcription
      and translation should be employed, such as the CMVint and pCIS-CAT constructs.
      Formulation aspects of cationic lipid-DNA complexes are being studied in several
      laboratories, and the physical properties and molecular organization of the
      complexes are being elucidated. Likewise, studies on the mechanism of DNA
      delivery with cationic lipids are accumulating which support the basic concept
      that the complexes fuse with biological membranes leading to the entry of intact
      DNA into the cytoplasm. Naked plasmid DNA administered by various routes is
      expressed at significant levels in vivo. This observation is not restricted to
      skeletal and heart muscle, but has been observed in lung, dermis, and in
      undefined tissues following intravenous administration. Most of the widely
      available cationic lipids, including Lipofectin, Lipofectamine and DC-cholesterol
      have a very poor ability to enhance DNA expression above the baseline naked DNA
      level, at least in lung. In this report we have revealed a novel cationic lipid,
      DLRIE, which can significantly enhance CAT expression in mouse lung by 25-fold
      above the naked DNA level. Other compounds are currently being evaluated which
      can enhance the naked DNA expression even higher. Plasmid vector improvements
      have led to further increase in in vivo lung expression, so that the net
      improvement is > 5,000-fold. Results of this nature are advancing the
      pharmaceutical gene therapy opportunities for synthetic cationic lipid based gene
      delivery systems.

PMID- 8546387
TI  - Overview of DNA vaccines.

PMID- 8546388
TI  - Immunological properties of bacterial DNA.

PMID- 8546389
TI  - Assuring the safety and efficacy of DNA vaccines.

PMID- 8546390
TI  - Regulatory issues in the use of DNA vaccines.

PMID- 8546391
TI  - Obtaining marketing authorization for nucleic acid vaccines in the European
      Union.
AB  - Nucleic acid vaccines are promising candidates for easy-to-handle and cost
      effective vaccines that combine the safety of subunit vaccines with the efficacy
      of live virus vaccines. In order to obtain marketing authorization for a nucleic
      acid vaccine in all member states of the European Union, a single application
      dossier has to be filed with the European Agency for the Evaluation of Medicinal
      Products. Notes for Guidance on the data necessary to support applications are
      available. The preclinical development of nucleic acid vaccines has to follow
      procedures of contained use according to the relevant EC directives which were
      translated into the German Gene Law. Clinical trials in Germany would follow the
      known procedures defined in the German Drug Law, whereas the Gene Law is not
      applicable. Clinical trials should be started only after having obtained consent
      of the Commission for Gene Therapy Trials formed under the auspices of the
      Federal Chamber of Physicians. Experience in intramuscular nucleic acid
      inoculation of animals has been gained using expression constructs comprising
      single and multiple genes of simian immunodeficiency virus. Specific antibodies
      were induced against multiple antigens. No adverse effects of nucleic acid
      inoculations were found, but more rigorous testing of specific safety problems
      will have to be performed.

PMID- 8546392
TI  - DNA inoculation induces cross clade anti-HIV-1 responses.
AB  - Nucleic acid or DNA immunization represents a novel approach to vaccine and
      immune therapeutic development. The direct injection of expression cassettes into
      a living host results in in vivo gene expression and immune activation. In the
      case of HIV-1 it has been shown by our laboratory that facilitated injection
      mimicks aspects of live attenuated vaccines and that both humoral and cellular
      responses can be induced upon injection of a nucleic acid sequence directly into
      a host target tissue. Antisera from HIV-1 plasmid expression cassette-immunized
      animals contain anti-HIV envelope glycoprotein immune responses. The antiserum
      neutralizes HIV-1 infection and inhibits cell to cell infection in vitro.
      Cellular immune responses have also been evaluated. We observed both T cell
      proliferation and isotype switching consistent with the production of relevant T
      helper immune responses in immunized animals. Furthermore it was demonstrated
      that CTL lysis of relevant env-expressing targets was similarly induced. These
      studies further define the importance of evaluating this new technology for
      vaccine and immune therapeutic development for HIV-1 as well as for other human
      viral pathogens.

PMID- 8546393
TI  - Cytotoxic T lymphocyte and helper T cell responses following HIV polynucleotide
      vaccination.
AB  - Expression vectors encoding either HIV-1 gp160/rev, gp120, or rev alone were used
      for direct vaccination of mice and nonhuman primates. Each vaccine elicited long
      lived (> 7 months) helper T cell responses in mice and monkeys as measured by in
      vitro proliferation of splenocytes following recombinant antigen treatment.
      Cytokine assays of the cell supernatants showed that approximately 100-fold more
      gamma-interferon than IL-4 was secreted during culture indicating that these
      vaccines elicited TH1-like responses. CD8+ CTL activities were also observed both
      in mice and rhesus. The gp120 and gp160/rev vaccines elicited antigen-specific
      antibodies, although these responses were more variable and lower magnitude for
      gp160/rev, and gp120 DNA-vaccinated African green monkeys had moderate levels of
      neutralizing antibodies. No antibodies were found against rev (an intracellular
      protein) with either rev vaccine. Similar antibody titers were obtained for gp120
      by either intramuscular or intradermal injection although T cell responses were
      generally lower by intradermal route. These results indicate that DNA vaccines
      may provide a powerful means to elicit cellular and humoral immune responses
      against HIV.

PMID- 8546394
TI  - Simian immunodeficiency virus DNA vaccine trial in macaques.

PMID- 8546395
TI  - Use of plasmid DNA for direct gene transfer and immunization.
AB  - Direct gene transfer by intramuscular injection of plasmid DNA encoding an
      antigenic protein may be used for the purpose of immunization. Several factors
      influence the uptake and expression of plasmid DNA in skeletal muscle, which in
      turn influence the immune response to the expressed protein. Physical barriers
      and other factors may impede the diffusion of the DNA within the muscle tissue or
      its entry into the muscle fibers. Although the efficiency of gene transfer in
      normal mouse muscle is low (< 100 fibers per injection site), both humoral and
      cell-mediated immune responses to the hepatitis B surface antigen (HBsAg) are
      obtained after the expression of a transferred gene, and these are dose
      dependent. The efficacy of the immune response can be improved by injection of
      the DNA in or following pretreatment with a hypertonic solution or with the local
      anesthetic bupivacaine, and even more so by injecting the DNA into regenerating
      muscle.

PMID- 8546397
TI  - Direct gene transfer for treatment of human cancer.
AB  - Genetic instability within malignant cells gives rise to mutant proteins which
      can be recognized by the immune system. Recognition of tumor-associated antigens
      by T lymphocytes could thus contribute to the elimination of neoplastic cells. We
      have developed a molecular genetic intervention for the treatment of malignancies
      based upon the knowledge that foreign major histocompatibility complex (MHC)
      proteins expressed on the cell surface are efficient at stimulating an immune
      response. Expression of this foreign MHC gene within tumors induced a cytotoxic T
      cell response to the introduced gene. More importantly, the immune system
      recognized tumor-specific antigens on unmodified tumor cells as foreign. Growth
      of the tumors diminished, and in many cases, there was complete regression. This
      research provides evidence that direct gene transfer in vivo can induce cell
      mediated immunity against specific gene products, and offers the potential for
      effective immunotherapy for the treatment of cancer and infectious diseases in
      man. Our laboratory conducted a phase I clinical trial to determine the safety
      and efficacy of this treatment in humans. These studies suggest that direct gene
      transfer provides a safe and feasible approach for the treatment of human cancer.
      More recent developments using combination gene therapy and the initiation of a
      second human trial with improvements on this technology have been implemented.
      Finally, we have begun to define mechanisms of resistance to immune recognition
      by established malignancies.

PMID- 8546396
TI  - A genetic approach to idiotypic vaccination for B cell lymphoma.
AB  - Idiotypic immunoglobulin expressed by a B cell tumor presents a clear tumor
      antigen which could be attacked by vaccination of the host. Vaccination with
      idiotypic protein has been shown to induce protective immunity against lymphoma,
      but application to patients is limited by the requirement of "personal" vaccines
      for each patient. A genetic approach enables V-region sequences encoding
      idiotypic antigen to be rescued from tumor biopsies, and to be assembled as scFv
      fragments. These can be expressed in bacteria to produce recombinant protein, or
      used directly as naked DNA vaccines. Intramuscular injection of idiotypic DNA
      from a mouse B cell lymphoma induces low levels of syngeneic anti-idiotypic
      antibody in serum. Response can be stimulated by co-injection of DNA plasmids
      encoding either IL-2 or GM-CSF, and T cells which proliferate in response to
      idiotypic IgM are generated. However, protection against tumor appears to be
      blocked by continuing secretion of idiotypic antigen from the persisting vaccine
      vector, which forms immune complexes with serum antibody. Methods for regulating
      the level of scFv to engage the immune system, but not to block the effector arm
      are being investigated. Similar control will be applicable to the cytokine
      vectors, which can deliver encoded cytokines designed to activate immune pathways
      for tumor destruction. Experience gained in lymphoma may be extended to other
      tumors with defined tumor antigens.

PMID- 8546398
TI  - Prospects for gene therapy with direct injection of polynucleotides.

PMID- 8546399
TI  - Nucleic acid vaccination against virally induced tumors.
AB  - Plasmid DNA (pSV3-neo) encoding the large tumor antigen (T-ag) of simian virus 40
      (SV40) was used to actively immunize mice to assess the induction of SV40 T-ag
      specific immunity. Mice were injected with naked DNA intramuscularly, and both
      the cellular and humoral immune responses were compared to those elicited in mice
      immunized with recombinant protein. Administration of recombinant SV40 T-ag
      elicited high titer antibodies reactive with SV40 T-ag, whereas inoculation with
      DNA failed to generate comparable levels of SV40 T-ag specific antibody.
      Conversely, antigen specific cytotoxic T lymphocyte activity was generated in
      mice immunized with pSV3-neo, but was not detected in mice immunized with the
      recombinant protein. Moreover, the cellular immunity generated by the injection
      of pSV3-neo DNA was protective against a lethal challenge with syngeneic SV40
      transformed cells. Together, these data indicate that active immunization with
      genes encoding tumor specific antigens may be an efficacious strategy for the
      induction of cell-mediated mechanism(s) to prevent cancer.

PMID- 8546400
TI  - Synthetic oligonucleotide does not bind to lipid emulsion resembling low-density
      lipoprotein.

PMID- 8546401
TI  - Protection against homologous influenza challenge by genetic immunization with
      SFV-RNA encoding Flu-HA.

PMID- 8546402
TI  - The immune response to HIV gp120 induced by nucleic acid immunization (NAI).

PMID- 8546403
TI  - Layered amplification of gene expression with a DNA gene delivery system.

PMID- 8546404
TI  - The induction of mucosal immunity in the female genital tract using gene-gun
      technology. Part 1: Antigen expression.

PMID- 8546405
TI  - Conjugates of glycosylated steroids and polyamines as novel nonviral gene
      delivery systems.
AB  - We have designed novel glycosteroid-polyamines for transmembrane DNA delivery
      based on amphiphilic drug transport agents. These glycosteroid-based agents show
      promise as viable DNA delivery technology for gene therapy.

PMID- 8546406
TI  - Plasmid DNA for human gene therapy and DNA vaccines. Production and quality
      assurance.

PMID- 8546407
TI  - neu/HER-2 cDNA vaccination and pregnancy loss.

PMID- 8546408
TI  - Nucleic acid vaccination with HIV regulatory genes.

PMID- 8546409
TI  - Immune responses to hepatitis B virus surface and core antigens in mice, monkeys,
      and pigs after Accell particle-mediated DNA immunization.

PMID- 8546410
TI  - Induction of antibodies against Salmonella typhi OmpC porin by naked DNA
      immunization.

PMID- 8546412
TI  - Protective efficacy of intramuscular immunization with naked DNA.

PMID- 8546411
TI  - Potential DNA vaccine integration into host cell genome.
AB  - Studies have been designed to examine the potential integration of DNA vaccines
      into the host cell genome. This is of concern because of the possibility of
      insertional mutagenesis resulting in the inactivation of tumor suppressor genes
      or the activation of oncogenes. The requirements for adequate testing were
      determined to be (1) a method to purify host cell genomic DNA from nonintegrated
      free plasmid, (2) a sensitive method to detect integrated plasmid in the purified
      genomic DNA, and (3) stringent methods to avoid contamination. These requirements
      were fulfilled by agarose-gel electrophoresis, the polymerase chain reaction, and
      separation of each activity with stringent handling procedures, respectively. An
      exploratory experiment was carried out in which mice were injected with 100
      micrograms of vaccine plasmid DNA in each quadriceps. Examination of quadriceps
      and 12 other tissues at several time points failed to reveal any evidence of
      integration at a sensitivity level that could detect 1 to 7.5 integrations in
      150,000 nuclei. A worst-case scenario determined that this would be at least 3
      orders of magnitude below the spontaneous mutation frequency.

PMID- 8546413
TI  - DNA immunization with bovine herpesvirus-1 genes.

PMID- 8546414
TI  - DNA-mediated immunization to the hepatitis B surface antigen. Activation and
      entrainment of the immune response.
AB  - The use of plasmid vectors expressing the HBsAg, along with improved protocols
      for transfection of muscle fibers (Refs. 3-6 and Davis et al., this volume), have
      provided the reagents and methods with which to investigate the characteristics
      of the strong immune response given by this antigen after DNA-mediated
      immunization. Analysis of the fine specificity of the humoral response provides
      support for the idea that the HBsAg-bearing particles are formed such that the B
      and T epitopes are presented to the immune system in a way resembling that of the
      natural viral or subviral particles. As shown here and elsewhere, DNA-mediated
      immunization with the HBsAg-expressing plasmid vectors induces strong CTL
      responses as well as a dominant Th1 phenotype among the splenic lymphocytes of
      immunized mice. The Th1 cytokine profile can be obtained in two different strains
      of mice and with two types of proteins, HBsAg and beta-galactosidase. One
      important line of investigation in the future will be to determine the mechanism
      of this generic Th1 response to DNA-based immunization. Circumstantial evidence,
      discussed by Pisetsky et al. (this volume), suggests that the chemical nature of
      DNA may play a role as an adjuvant (see also Ref. 31), and this hypothesis to
      explain the cytokine profiles observed after DNA-mediated immunization must now
      be taken seriously. All the questions raised by this novel method of immunization
      are of interest for the design of future vaccines, even if DNA itself is
      ultimately not the vaccinating moiety. The question of antigen presentation is
      particularly intriguing, since the small amounts of protein produced by DNA
      mediated immunization (on the order of nanograms) are capable of inducing strong
      immune responses at the level of B and T cells. Although initially it seemed
      obvious that endogenous protein synthesis in cells transfected with plasmid DNA
      would account for the observed induction of CTL activity, this idea must be
      examined in light of two well established sets of experimental results. First,
      the primary events in activation of CD8+ (as well as CD4+) T lymphocytes normally
      require professional APC capable of furnishing co-stimulatory signals to
      supplement the consequences of interaction of the T-cell receptor with MHC
      surface molecules. Second, endogenous synthesis and processing is not the only
      mechanism of class I epitope presentation, and numerous examples are now known
      whereby particulate exogenous proteins, such as HBsAg, can be taken up and
      processed in such a way as to allow class I presentation of peptides.
      Consideration of these two points suggests that a major contribution to the
      observed CTL induction afforded by DNA-mediated immunization could come from the
      sustained presence of the antigenic protein in interstitial spaces or in the
      circulation, coupled with the ability of the exogenous protein to be processed
      for class I presentation. This could be true for many other proteins in addition
      to the HBsAg. This hypothesis eliminates the inconvenient notion that muscle
      fibers (or other nonleukocyte cells) present antigen in a way compatible with
      primary activation of T cells. However, muscle tissue can be an important
      reservoir of the antigen because of the potential for prolonged synthesis of the
      protein; this could therefore explain the immune entrainment observed after DNA
      mediated immunization. Muscle fibers or other cells could also serve to present
      class I epitopes for the purpose of restimulating and thus expanding the pool of
      activated CD8+ T lymphocytes. These explanations, though certainly plausible,
      will require experimental investigation. The small numbers of the transfected
      cells in vivo, as well as the potential mobility of transfected cells other than
      muscle fibers, may well render such experimentation difficult. DNA-mediated
      immunization clearly offers opportunities for obtaining novel insights into
      immunological mechanisms and immunization processes. It is also likely to promote
      vacc

PMID- 8546415
TI  - Plasmid vectors as anti-viral vaccines.

PMID- 8546416
TI  - Nucleic acid malaria vaccines. Current status and potential.

PMID- 8546418
TI  - Tracheotomy in children with juvenile-onset recurrent respiratory papillomatosis:
      the Children's Hospital of Pittsburgh experience.
AB  - Despite the risk of airway obstruction, tracheotomy has been viewed with
      trepidation in the management of recurrent respiratory papillomatosis (RRP). The
      literature suggests that the injury associated with the tracheotomy site may
      initiate the progression of disease to the distal airway. Alternatively, patients
      who require tracheotomy for RRP may be predisposed to distal spread because of
      more aggressive disease. In an effort to clarify this issue, we reviewed the
      Children's Hospital of Pittsburgh experience with 35 patients with RRP between
      1984 and 1994; 13 patients received tracheotomies. Tracheotomy patients presented
      at a younger age with more widespread disease, often involving the distal airway
      prior to tracheotomy. Although distal spread occurred in 50% of patients, it was
      generally limited to the tracheotomy site. Overall, outcome in the tracheotomy
      group was satisfactory. Complications related to the tracheotomy were rare. We
      conclude that tracheotomy is an appropriate option for significantly airway
      compromise in patients with RRP.

PMID- 8546417
TI  - Adenovirus and adeno-associated virus as vectors for gene therapy.

PMID- 8546419
TI  - Visualizing the pediatric airway: three-dimensional modeling of endoscopic
      images.
AB  - Three-dimensional reconstruction of medical images has emerged as an important
      visualization tool for studying complex anatomy. These tools have found important
      applications in neurology and plastic surgery using computed tomography (CT) and
      magnetic resonance imaging (MRI) data. However, CT and MRI do not sufficiently
      delineate lesions of the pediatric airway. Inspection through the rod lens
      telescope remains the standard diagnostic method. A video recording of an
      endoscopic procedure is essentially a sequence of two-dimensional images captured
      as the telescope traverses the airway lumen. Using digitized endoscopic video
      recordings and computer graphics reconstruction techniques, we have developed a
      preliminary three-dimensional modeling system for the pediatric airway. A series
      of normal and abnormal telescopic airway examinations were video recorded. Serial
      sections were obtained by digitizing the video images at uniform intervals as the
      scope traversed the airway lumen between the vocal folds and the carina. The
      digitized images were calibrated and used to reconstruct the airway lumen in
      three dimensions. Classifying airway abnormalities according to the minimal cross
      sectional area or with descriptive terms can be subjective and dependent on the
      endoscopist's observational skills. We hope that this preliminary work will lead
      to more precise and understandable methods for representing complex airway
      lesions.

PMID- 8546420
TI  - Supraglottic laryngectomy: functional and oncologic results.
AB  - Between January 1980 and December 1989, 110 patients with squamous cell carcinoma
      of the supraglottis were treated with supraglottic laryngectomy and neck
      dissection. The stage distribution was stage I 23%, II 34%, III 15%, and IV 28%.
      Adjuvant radiotherapy (5,000 to 6,500 cGy) was given to all pN+cases. All
      patients were followed until death or for a minimum of 36 months, with an average
      of 65 months. Decannulation was achieved in 96% of the cases, with only 1 patient
      undergoing total laryngectomy because of aspiration. The average hospital stay
      was 22 days. Arytenoid edema was a frequent cause of delayed decannulation in
      patients undergoing radiotherapy. The overall 3-year survival was 78%, with 10
      patients dying of unrelated causes. Local control was 94.6% and regional control
      was 83.6%. No significant difference was found in survival according to T stage,
      but survival rate was significantly influenced by N stage.

PMID- 8546421
TI  - Respiratory manifestations of gastroesophageal reflux disease in pediatric
      patients.
AB  - Respiratory manifestations of gastroesophageal reflux disease (GERD) are being
      recognized with increasing frequency. We present the evaluation and management of
      four infants and children with unusual respiratory symptoms attributed to GERD.
      The advantages and disadvantages of diagnostic studies of GERD are discussed, and
      an evaluation and treatment protocol is presented. Treatment must be tailored to
      the nature and severity of the patient's presenting symptoms and includes
      conservative, pharmacologic, and/or surgical management.

PMID- 8546422
TI  - Long-term effects of botulinum toxin injections in spasmodic dysphonia.
AB  - The purpose was to examine whether physiological changes can be found in
      laryngeal muscles following repeated treatment with botulinum toxin injections in
      spasmodic dysphonia. Seven patients whose treatment consisted of multiple
      unilateral thyroarytenoid injections were examined more than 6 months following
      their most recent botulinum toxin injection fiberoptic laryngoscopy and
      electromyography. Comparisons were made between injected and contralateral
      noninjected muscles' motor unit characteristics, muscle activation patterns, and
      vocal fold movement characteristics. The results demonstrated that motor unit
      characteristics differed between injected and noninjected muscles and that these
      differences were greater in patients less than 12 months since last injection.
      Motor unit duration differences were reduced and motor unit amplitude and numbers
      of turns were increased in muscles sampled over 1 year after injection. These
      results suggest that while the physiologic effects of botulinum toxin are
      reversible, the reinnervation process continues past 12 months following
      injection.

PMID- 8546423
TI  - Vertical plane short and middle latency vestibular evoked potentials in humans.
AB  - In order to determine whether short and middle latency vestibular evoked
      potentials (VsEPs) can be recorded in humans in response to angular acceleration
      stimuli in the vertical plane, a drum, head-holder, and stepper motor were
      designed to deliver upward acceleration impulses of 10,000 degrees/s2 (1.8
      degrees displacement) to the human head. Forehead and mastoid electrodes recorded
      electrical activity that was filtered, differentially amplified, and averaged in
      short (12.7 milliseconds) and middle (63.5 milliseconds) latency time frames.
      Control recordings were used to eliminate various types of artifact. Recordings
      were conducted in 7 normal subjects and in 4 control patients with congenital,
      profound hearing loss and absence of caloric responses. Short and middle latency
      VsEPs with high intrasubject and intersubject consistency were recorded in normal
      subjects and not in control patients. The middle latency responses were larger in
      amplitude than the short latency responses. The effects of stimulus intensity and
      repetition rate on VsEP waveform, latency, and amplitude studied. Experiments
      have shown that the responses are not electrical artifact, nor are they
      contaminated by auditory, somatosensory, or passive eye movement potentials.

PMID- 8546424
TI  - Role of herpes simplex virus infection in the pathogenesis of facial paralysis in
      mice.
AB  - To clarify the role and site of herpes simplex virus (HSV) infection in the
      pathogenesis of facial paralysis, we examined the viral genome by the polymerase
      chain reaction and the neutralization antibody titer using microplates in an
      animal model. Following inoculation with HSV type 1 of the KOS strain into mouse
      auricles, HSV DNA appeared in the ipsilateral facial nerve on the 3rd day, and in
      bilateral facial nerves and the brain stem on the 10th day only in animals with
      facial paralysis. In animals without facial paralysis, no HSV DNA was detected in
      these tissues. The neutralization antibody titer was elevated between 4 and 20
      days in all animals, with or without facial paralysis. Facial paralysis developed
      only on the inoculated side, even though HSV DNA was also present in the
      contralateral facial nerve. We conclude that HSV infection in the facial nerve
      and brain stem is prerequisite for facial paralysis, and suggest that an
      immunologic reaction following viral infection plays a key role in the
      pathogenesis.

PMID- 8546425
TI  - Comparative perilymph permeability of cephalosporins and its significance in the
      treatment and prevention of suppurative labyrinthitis.
AB  - Cephalosporins are nonototoxic antibiotics that provide excellent coverage for
      almost all bacteria that can cause suppurative labyrinthitis. In this study we
      performed comparative perilymph permeability determinations of the three
      cephalosporins that we deemed to have the most clinical potential in these varied
      situations. Perilymph pharmacokinetic profiles were established for ceftazidime,
      cefuroxime, and cefotaxime and its metabolite desacetylcefotaxime in 36 guinea
      pigs by using the technique of high-performance liquid chromatography. At 1, 2,
      3, 4, and 6 hours after intravenous administration of the three cephalosporins at
      a dose of 100 mg/kg of body weight, ceftazidime consistently exhibited the
      highest perilymph concentration. Desacetylcefotaxime showed the next highest
      capacity for penetration into perilymph. Keeping in mind that the choice of drug
      for the treatment of suppurative labyrinthitis should be based foremost on
      culture and sensitivity studies, we consider ceftazidime to be the first-line
      agent for treatment and prevention of both meningogenic labyrinthitis and
      labyrinthitis complicating acute or chronic otitis media.

PMID- 8546426
TI  - Acute otitis media and facial paralysis in children.
AB  - We reviewed 10 children who presented with facial paralysis after the onset of
      acute otitis media. The objective of the study was to examine the outcome of
      facial paralysis in children with acute otitis media treated without facial nerve
      decompression. Two groups were identified: 8 patients with incomplete paralysis
      and 2 with complete paralysis. Seven of the 8 patients with incomplete paralysis
      had rapid return of function after myringotomy and intravenous antibiotics. The
      eighth patient had delayed recovery requiring 9 months before complete return of
      function. The 2 patients with complete paralysis required mastoidectomy to
      control otorrhea and fever after initial myringotomy and antibiotics. Both
      patients had a prolonged recovery requiring 3 and 7 months for complete recovery.
      Patients with incomplete paralysis generally show rapid improvement following
      wide myringotomy and antibiotic treatment. A more protracted recovery may be
      expected in patients with complete paralysis; excellent return of function is
      expected when mastoidectomy without facial nerve decompression is employed.

PMID- 8546427
TI  - Immunocytochemical study of proteoglycans in vocal folds.
AB  - We evaluated the proteoglycan composition of normal vocal folds using
      immunocytochemical techniques. Frozen sections of 14 normal cadaveric vocal folds
      were obtained within 12 hours of death and sectioned immediately. Vocal fold
      sections were stained with antibodies against keratan sulfate, chondroitin
      sulfate, heparan sulfate proteoglycan (HSPG), decorin, and hyaluronate receptor.
      We found that the lamina propria has diffuse staining of fibrillar components
      with keratan sulfate and decorin. Intense staining was observed in the vocal
      ligament area with keratan sulfate. The HSPG was localized to be basement
      membrane zone. Chondroitin sulfate, HSPG, and hyaluronate receptor were detected
      in the cytoplasm of interstitial cells with immunocytochemical characteristics of
      macrophages. The keratan sulfate distribution suggests that fibromodulin may be
      significant in normal vocal folds. Production of HSPG and probably versican
      occurs in macrophages and fibroblasts in the lamina propria.

PMID- 8546428
TI  - Clinical evaluation of extracorporeal shock wave lithotripsy for salivary stones.
AB  - The treatment of sialolithiasis is discussed in this report. Generally, stones
      within the distal salivary duct are easily removed by transoral ductotomy,
      although proximal stones are usually treated by excision of the salivary gland
      and its duct. Since 1980, extracorporeal shock wave lithotripsy (ESWL) has been
      in clinical use for the treatment of renal and gallbladder stones. We used this
      technique as a treatment for sialolithiasis. We undertook ESWL on 14
      submandibular gland stone patients and 1 parotid gland stone patient, clinical
      symptoms such as pain and swelling disappeared without excision of the affected
      salivary gland. Stones larger than 10 mm seem to have a tendency to form
      Steinstrassen. Although computed tomography findings correlate with success in
      breaking up gallstones, they did not predict success for salivary stones. We
      conclude that sialolithiasis is treated successfully without adverse effects by
      ESWL in selected patients.

PMID- 8546429
TI  - Epistaxis balloon catheter stabilization of zygomatic arch fractures.
AB  - Isolated zygomatic arch fractures represent about 10% of facial fractures. Most
      are easily reduced, but about 7% require fixation. Stabilization with plates,
      transcutaneous wiring, and various packing materials may involve additional
      morbidity and other drawbacks. A double balloon epistaxis catheter may be
      inserted beneath the arch fracture site and inflated for 5 to 7 days as a
      relatively simple, reliable alternative that involves minimal morbidity.

PMID- 8546430
TI  - Prostate cancer metastatic to the orbit.

PMID- 8546431
TI  - Pediatric craniocervical necrotizing fasciitis.

PMID- 8546432
TI  - Basaloid squamous cell carcinoma of the head and neck: clinicopathological
      features and differential diagnosis.
AB  - Basaloid squamous cell carcinoma is a recently recognized variant of squamous
      cell carcinoma. The lesion is histologically distinctive and manifests a
      predilection for the supraglottis, pyriform sinus, and tongue base. The
      immunohistochemical profile is discussed. The differential diagnoses include
      adenoid cystic carcinoma, small cell neuroendocrine carcinoma, basal cell
      adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, spindle cell
      squamous carcinoma, mucoepidermoid carcinoma, and adenoid squamous cell
      carcinoma. Basaloid squamous cell carcinoma is a biologically high-grade tumor
      with a propensity for nodal as well as systemic metastases. It is a morphologic
      and phenotypic entity with a separate prognostic significance.

PMID- 8546433
TI  - Are papillary adenomas endolymphatic sac tumors?

PMID- 8546434
TI  - Surgical results of lumbar spinal stenosis.
AB  - The purpose of this work was to evaluate the surgical results of lumbar spinal
      stenosis (LSS), and to find factors which influenced outcome. A total of 497 LSS
      patients fulfilled the inclusion criteria i.e. LSS was confirmed both
      radiologically and surgically, in the study period from 1974 to 1987. For various
      reasons 58 patients could not participate in the study, and hence, the results of
      this work were based on 439 surgically treated LSS patients. An excellent-to-good
      outcome was achieved in 62% of all patients with a mean follow-up time of 4.3
      years. The prognostic factors for this result were able to work after surgery,
      able to work before surgery, no prior back surgery, age over 50 years, male sex,
      and leg pain. Of 86 patients who were working before surgery, 52 (60%) continued
      to work after operation, whereas of 223 patients who were on sick leave before
      surgery, 70 (31%) returned to work after operation. None of the preoperatively
      retired patients regained their ability to work postoperatively. The prognostic
      factors for ability to work after surgery were ability to work before surgery,
      age under 50 years, and no prior back surgery. The very long-term outcome (mean
      followup time of 12.4 years) was excellent-to-good in 68% of patients (59% women
      and 73% men). Furthermore, in the longitudinal follow-up, the result improved
      between 1985 (mean follow-up time 6.8 years) and 1991 (mean follow-up time 12.8
      years). No special complications were manifested during this very long-term
      follow-up time. The patients with total or subtotal block in preoperative
      myelography achieved the best result. In this radiological category of LSS the
      proportion of patients with excellent-to-good outcome was very similar in women
      and men (73% and 77%). Furthermore, patients with block stenosis improved their
      result significantly in the longitudinal follow-up. The postoperative stenosis
      seen in computed tomography (CT) scans was observed in 65% of 90 patients, and it
      was severe in 23 patients (25%). However, this successful or unsuccessful
      surgical decompression did not correlate with patients' subjective disability,
      walking capacity or severity of pain. Previous back surgery had a strong
      worsening effect on surgical results. This effect was very clear in patients with
      total block in the preoperative myelography. The surgical result of a patient
      with previous back surgery was similar to that of a patient without previous back
      surgery when the time interval between the last two operations was more than 18
      months.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8546435
TI  - Effect of postexercise sucrose administration on liver glycogen repletion in
      rats.
AB  - In Wistar rats after swimming for 3 h, the glycogen level remained low in the
      liver during a period of 7 h. When sucrose was administered immediately after
      exercise, the liver glycogen content increased rapidly. From the 3rd to the 5th
      postexercise hour a secondary reduction was observed in hepatic glycogen. Sucrose
      administration inhibited the reduction of the blood glucose concentration which
      increased during exercise. However, 7 h after exercise, a slight hypoglycemia
      occurred in sucrose-treated rats. Administration of sucrose as a bolus
      immediately after exercise does not ensure a complete refilling of the hepatic
      glycogen store.

PMID- 8546436
TI  - Vitamin intakes (A, E, C, carotenes) in a French institution: assessment by the
      duplicate-diet method.
AB  - Duplicate meals of those eaten by 14 healthy young males (25-35 years of age),
      usual hospital diets for breakfast, lunch, and dinner, were collected for 5
      consecutive days and freeze-dried. Fat-soluble vitamin (alpha-, beta-, gamma-,
      and delta-tocopherols, retinol, alpha- and beta-carotenes) and vitamin C contents
      were analyzed. Duplicate meals presented a wide range in vitamin levels. Large
      individual day-to-day variations were observed. The median daily intakes (n =70)
      of retinol equivalent (0.31 mg/day) and tocopherol equivalent (3.48 mg/day) were
      low. Only one third of the meals could provide sufficient amounts of fat-soluble
      vitamins, whereas vitamin C intakes were adequate (87.4 mg/day). So, fat-soluble
      recommended intakes were not supplied for most of the subjects in this study.

PMID- 8546438
TI  - Determination of riboflavin and flavocoenzymes in human blood plasma by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic method for determining riboflavin,
      flavin adenine dinucleotide, and flavin mononucleotide in human blood plasma is
      presented. Flavocoenzymes are determined as flavin mononucleotide after acid
      hydrolysis of flavin adenine dinucleotide. Metabolites are separated by reversed
      phase column chromatography and quantified by their native fluorescence. Criteria
      of quality are (riboflavin/flavocoenzymes): coefficients of variation 2.8/4.6%
      (intra-assay) and 2.8/4.4% (inter-assay); recovery 82.4/94.4%; detection limit <
      3.0/9.0 nmol/l. Because sample preparation requires only few steps, and the
      retention times are short ( < 5 min), this method is recommended for use in
      routine analysis.

PMID- 8546437
TI  - Magnesium and ascorbic acid supplementation in diabetes mellitus.
AB  - The effect of magnesium (Mg) and ascorbic acid (AA) supplementation on metabolic
      control was assessed in 56 outpatient diabetics. A 90-day run-in period was
      followed by two 90-day treatment periods, during which Mg (600 mg/day) and AA (2
      g/day) were administered in a randomized double-blind cross-over fashion. A
      decrease in systolic and diastolic blood pressure (132 +/- 3 vs. 138 +/- 4 and 77
      +/- 2 vs. 82 +/- 2 mm Hg; p < 0.05) was observed in insulin-dependent diabetes
      mellitus subjects during Mg supplementation. No beneficial effect of Mg
      supplementation was observed on glycemic control, lipids or blood pressure in non
      insulin-dependent diabetes mellitus (NIDDM) subjects. AA supplementation improved
      glycemic control among NIDDM subjects and both fasting blood glucose (9.1 +/- 0.5
      vs. 10.1 +/- 0.6 mmol/l; p < 0.05) and HbA1c (8.5 +/- 0.3 vs. 9.3 +/- 0.3%; p <
      0.05) improved. Beneficial effects of AA supplementation on cholesterol (5.9 +/-
      0.2 vs. 6.2 +/- 0.2 mmol/l; p < 0.05) and triglycerides (2.2 +/- 0.2 vs. 2.5 +/-
      0.2; p < 0.05) were also observed in NIDDM subjects. The results suggest that
      high-dose AA supplementation may have a beneficial effect in NIDDM subjects on
      both glycemic control and blood lipids.

PMID- 8546439
TI  - Copper malabsorption after intestinal resection in rats. Effects of
      cholecalciferol and ascorbic acid.
AB  - Dietary modifications can partly compensate for the alterations in copper
      homeostasis caused by distal intestinal resection, by improving biliary function.
      We studied the effects of resecting 50% of the distal small intestine (DSI) on
      copper status in rats fed three semisynthetic diets (basal diet, and basal diet
      with cholecalciferol or ascorbic acid). Intestinal resection significantly
      decreased the digestive (apparent digestibility coefficient; ADC) and metabolic
      utilization (balance) of copper 1 month after surgery. However, the
      supplementation of the basal diet with cholecalciferol attenuated the negative
      impact of surgery, leading to small differences in Cu ADC and Cu balance between
      transected and resected rats. Ascorbic acid also enhanced copper retention.
      Copper status was not as markedly affected by intestinal resection as digestive
      utilization 1 month after the operation. The beneficial effects of
      cholecalciferol and ascorbic acid at the digestive and metabolic levels suggest
      ways to lessen the impact of intestinal resection, and to avoid possible long
      term postabsorptive alterations in copper distribution.

PMID- 8546440
TI  - Validity of predicted total body water and extracellular water using
      multifrequency bioelectrical impedance in an Ethiopian population.
AB  - Total body water (TBW) and extracellular water (ECW) were measured by deuterium
      oxide dilution and bromide dilution, respectively, in a group of 24 male and 20
      female healthy Ethiopians, living in the capital Addis Ababa. Body weight, body
      height, skinfolds and total body impedance at 1 and at 100 kHz were also
      measured. TBW and ECW were predicted from impedance values at 1 and 100 kHz,
      respectively, using prediction equations developed in a Dutch adult population.
      ECW was overestimated by 1.3 +/- 1.0 kg (p < 0.05) and 0.6 +/- 0.8 kg (p < 0.05)
      in males and females, respectively. TBW was accurately predicted in males (0.1 +/
      1.9 kg, n.s.), but overestimated in females (1.0 +/- 1.3 p < 0.05). TBW/height
      and ECW/height were substantially lower in the Ethiopians compared to values
      recently published in Dutch and Italian adult subjects, indicating a different,
      more slender body build of the Ethiopians. After correcting for these differences
      in body build and for the slight differences in body water distribution
      (ECW/TBW), the differences between measured and predicted TBW and ECW decreased
      and were no longer significant. The results indicate that the validity of
      predicted body water from impedance depends on the body build of the subjects,
      which should be taken into account to avoid systematic errors when applying
      prediction formulas from a reference population to another population under
      study.

PMID- 8546441
TI  - Validation of extracellular water determination by bioelectrical impedance
      analysis in growth hormone-deficient adults.
AB  - We validated the determination of extracellular water (ECW) by the bioelectrical
      impedance method (BIA), using the RJL manufacturer-supplied equation and the
      equation of Lukaski in 34 growth hormone-deficient (GHD) patients before and
      after replacement with recombinant human growth hormone (rhGH), using the bromide
      dilution (Br-) method as the reference method. At baseline, paired comparisons
      showed no significant differences between mean ECW assessed by the Br- method and
      by BIA using both equations in the placebo and rhGH group. At 6 months, no
      significant difference was found between ECW assessed by the Br- method and by
      BIA using the manufacturer-supplied equation, both in the placebo and rhGH group.
      High coefficients of reliability (0.88-0.98) and high correlations (0.79-0.98; p
      < 0.001) were found between ECW assessed by the Br- method and by BIA applying
      two different regression equations in the placebo and rhGH groups at baseline and
      after 6 months. Mean differences in ECW assessed by the Br- method and BIA were
      between 2.6 and 4.1% of the mean ECW determined by the Br- method at baseline and
      between 2.7 and 8.5% after 6 months. Multiple comparisons showed a significantly
      greater ECW assessed by the Br- method than by BIA using the equation of Lukaski
      (p < 0.0001). This difference was found in the placebo and rhGH replacement
      group. The difference changed with time (p = 0.005), indicating that the
      usefulness of the formula of Lukaski seems to be affected by rhGH replacement
      therapy. We conclude that the noninvasive BIA technique might be a useful method
      to predict ECW in GHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8546443
TI  - Host immunity to ticks.
AB  - The tick-host-pathogen interface is characterized by complex immunological
      interactions. Tick feeding induces host immune regulatory and effector pathways
      involving antibodies, complement, antigen-presenting cells, T lymphocytes, and
      other bioactive molecules. Acquired resistance impairs tick engorgement, ova
      production, and viability. Tick countermeasures to host defenses reduce T
      lymphocyte proliferation, elaboration of the TH1 cytokines interleukin-2 and
      interferon-gamma, production of macrophage cytokines interleukin-1 and tumor
      necrosis factor, and antibody responses. The dynamic balance between acquired
      resistance and tick modulation of host immunity affects engorgement and pathogen
      transmission. A thorough understanding of acquired immunity to ticks is essential
      for rational development of antitick vaccines.

PMID- 8546442
TI  - Serum phospholipid fatty acids in severely injured patients on total parenteral
      nutrition with medium chain/long chain triglyceride emulsions.
AB  - The final goals of parenteral nutrition of severely injured patients is to
      satisfy energy and nitrogen requirements and simultaneously to prevent deficiency
      of essential nutrients as well as to reduce trauma-related metabolic
      disturbances. To evaluate clinical benefits either by a combination of
      carbohydrates and a medium-chain/long-chain triglyceride (MCT/LCT) lipid emulsion
      versus carbohydrates as the sole energy donor, 24 ventilated patients with
      multiple injuries and major head trauma were investigated. All patients received
      an isocaloric, isonitrogenous total parenteral nutrition (TPN) regimen consisting
      of either a no-lipids carbohydrate regimen (CH regimen) or a combined regimen of
      carbohydrates plus MCT/LCT emulsion (CH + MCT/LCT regimen), for 8 days in equal
      groups in the format of a prospective randomized study. After 5 days on the CH
      regimen, serum phospholipid measurements suggested linoleic acid deficiency and
      after 7 days alpha-linolenic acid deficiency. As a consequence significant
      decreases in the concentrations of both the n-6 and n-3 fatty acids along with a
      compensatory increase in nonessential n-9 fatty acids were observed. By contrast,
      the CH + MCT/LCT regimen maintained the concentrations of phospholipid linoleic
      acid and alpha-linolenic acid, thus preventing fatty acid pattern imbalances. The
      linoleic acid and alpha-linolenic acid metabolite balance was similarly
      maintained with the CH + MCT/LCT regimen.

PMID- 8546444
TI  - Evolution of ticks.
AB  - Evolutionary patterns in ticks have traditionally been cast in terms of host
      associations. Largely untested assumptions of cospeciation and observations of
      current host associations are used to estimate the age of different taxa. Several
      recent phylogenetic studies of supraspecific relationships in ticks, based on
      both morphological and DNA-sequence data, allow the first rigorous testing of
      these assumptions. Reanalysis of patterns of tick-host associations suggests that
      the perception of host specificity in ticks may be an artifact of incomplete
      sampling. An analysis of tick-host and -habitat associations and biogeographical
      patterns, in the context of the newly derived phylogenies, suggests that much of
      the existing host-association patterns may be explained as artifacts of
      biogeography and ecological specificity.

PMID- 8546445
TI  - Ion channels as targets for insecticides.
AB  - Ion channels are the primary target sites for several classes of natural and
      synthetic insecticidal compounds. The voltage-sensitive sodium channel is the
      major target site for DDT and pyrethroids, the veratrum alkaloids, and N
      alkylamides. Recently, neurotoxic proteins from arthropod venoms, some of which
      specifically attack insect sodium channels, have been engineered into
      baculoviruses to act as biopesticides. The synthetic pyrazolines also primarily
      affect the sodium channel, although some members of this group target neuronal
      calcium channels as well. The ryanoids have also found use as insecticides, and
      these materials induce muscle contracture by irreversible activation of the
      calcium-release channel of the sarcoplasmic reticulum. The arylheterocycles (e.g.
      endosulfan and fipronil) are potent convulsants and insecticides that block the
      GABA-gated chloride channel. In contrast, the avermectins activate both ligand-
      and voltage-gated chloride channels, which leads to paralysis. At field-use
      rates, a neurotoxic effect of the ecdysteroid agonist RH-5849 is observed that
      involves blockage of both muscle and neuronal potassium channels. The future use
      of ion channels as targets for chemical and genetically engineered insecticides
      is also discussed.

PMID- 8546446
TI  - Development of recombinant baculoviruses for insect control.
AB  - In this review, we provide an overview of the current status of recombinant
      baculoviruses, describe the development of genetically engineered baculoviruses
      for use as rapid-action biological insecticides, and provide more detailed
      information on one particular set of recombinant viruses. The advantages and
      disadvantages of recombinant baculovirus insecticides, and the importance of risk
      assessment studies of these genetically modified organisms, are reviewed. Finally
      the importance of sensible regulatory strategies to the success and future
      prospects of this technology is discussed.

PMID- 8546447
TI  - Culicoides variipennis and bluetongue-virus epidemiology in the United States.
AB  - The bluetongue viruses are transmitted to ruminants in North America by
      Culicoides variipennis. US annual losses of approximately $125 million are due to
      restrictions on the movement of livestock and germplasm to bluetongue-free
      countries. Bluetongue is the most economically important arthropod-borne animal
      disease in the United States. Bluetongue is absent in the northeastern United
      States because of the inefficient vector ability there of C. variipennis for
      bluetongue. The vector of bluetongue virus elsewhere in the United States is C.
      variipennis sonorensis. The three C. variipennis subspecies differ in vector
      competence for bluetongue virus in the laboratory. Understanding C. variipennis
      genetic variation controlling bluetongue transmission will help identify
      geographic regions at risk for bluetongue and provide opportunities to prevent
      virus transmission. Information on C. variipennis and bluetongue epidemiology
      will improve trade and provide information to protect US livestock from domestic
      and foreign arthropod-borne pathogens.

PMID- 8546448
TI  - Discontinuous gas exchange in insects.
AB  - Many insects exchange respiratory gases cyclically and discontinuously. A typical
      discontinuous gas exchange cycle (DGC) starts with a closed-spiracle (C) phase,
      during which little external gas exchange takes place, followed by a fluttering
      spiracle (F) phase, which is usually dominated by diffusive oxygen uptake. The
      DGC is terminated by an open-spiracle (O) phase, during which accumulated CO2
      escapes. This review critically examines the applicability of the DGC to insect
      gas exchange in general, discusses the primary mechanisms of gas exchange in the
      F and O phases, evaluates the widespread hypothesis that the DGC lowers
      respiratory water loss rates adaptively, and proposes new hypotheses concerning
      the evolutionary genesis of the DGC in insects and other tracheate arthropods.

PMID- 8546449
TI  - Assessment of phenotypic and genetic diversity in the yeast genus Metschnikowia.
AB  - The taxonomy of the yeast genus Metschnikowia has undergone profound changes over
      the past century. Major developments, from the capacity to obtain pure cultures
      of parasitic species to progress associated with the extensive use of molecular
      biology tools in yeast systematics, are briefly reviewed. Results from past work
      and new data are combined to evaluate evolutionary relationships and clarify the
      classification of both terrestrial and aquatic species. Recent physiological
      studies, including the utilization of non-conventional carbon and nitrogen
      sources, and characteristics like lipolytic activity and maximum temperatures for
      growth, are presented. The assessment of the genetic diversity within the genus
      by restriction analysis of the mitochondrial DNA and by the production of
      specific DNA probes has been explored. The results indicate the potential
      application of the latter in rapid identification procedures.

PMID- 8546450
TI  - Saccharomyces barnetti and Saccharomyces spencerorum: two new species of
      Saccharomyces sensu lato (van der Walt).
AB  - In the course of a study of DNA base sequence homology, 19 strains labelled as
      Saccharomyces exiguus, its imperfect state, Candida holmii, or C. milleri were
      examined. Results confirmed the separation of C. milleri as a separate species.
      The remaining strains can be divided into three distinct groups of genomic
      relatedness. The type cultures of S. exiguus and C. holmii form a cluster with 10
      other strains showing variable reassociation values ranging from 100 to 40%. The
      remaining four strains comprise two separate species showing no nucleotide
      relatedness between themselves nor to either the S. exiguus complex or to C.
      milleri. Physiological analyses demonstrate that it is possible to separate these
      four taxa on the basis of a few simple tests. The two new species are described
      respectively as Saccharomyces barnetti honoring James Barnett in recognition of
      his invaluable work in the field of yeast taxonomy and Saccharomyces spencerorum
      in honor of J.F.T. and Dorothy M. Spencer who have made innumerable contributions
      to the genetics and biotechnological application of yeasts.

PMID- 8546452
TI  - Yeast communities in a natural tequila fermentation.
AB  - Fresh and cooked agave, Drosophila spp., processing equipment, agave molasses,
      agave extract, and fermenting must at a traditional tequila distillery
      (Herradura, Amatitan, Jalisco, Mexico) were studied to gain insight on the origin
      of yeasts involved in a natural tequila fermentations. Five yeast communities
      were identified. (1) Fresh agave contained a diverse mycobiota dominated by
      Clavispora lusitaniae and an endemic species, Metschnikowia agaveae. (2)
      Drosophila spp. from around or inside the distillery yielded typical fruit
      yeasts, in particular Hanseniaspora spp., Pichia kluyveri, and Candida krusei.
      (3) Schizosaccharomyces pombe prevailed in molasses. (4) Cooked agave and extract
      had a considerable diversity of species, but included Saccharomyces cerevisiae.
      (5) Fermenting juice underwent a gradual reduction in yeast heterogeneity.
      Torulaspora delbrueckii, Kluyveromyces marxianus, and Hanseniaspora spp.
      progressively ceded the way to S. cerevisiae, Zygosaccharomyces bailii, Candida
      milleri, and Brettanomyces spp. With the exception of Pichia membranaefaciens,
      which was shared by all communities, little overlap existed. That separation was
      even more manifest when species were divided into distinguishable biotypes based
      on morphology or physiology. It is concluded that crushing equipment and must
      holding tanks are the main source of significant inoculum for the fermentation
      process. Drosophila species appear to serve as internal vectors. Proximity to
      fruit trees probably contributes to maintaining a substantial Drosophila
      community, but the yeasts found in the distillery exhibit very little similarity
      to those found in adjacent vegetation. Interactions involving killer toxins had
      no apparent direct effects on the yeast community structure.

PMID- 8546453
TI  - Xanthomonas campestris pv. parthenii pathovar nov. incitant of leaf blight of
      parthenium.
AB  - A new bacterial leaf blight disease of parthenium (Parthenium hysterophorus L.)
      is described for the first time. The disease-causing bacterium was isolated and
      its morphological, physiological and biochemical characters were determined. The
      pathogenicity of bacterium is apparently limited only to parthenium. The pathogen
      was identified as Xanthomonas campestris pv. parthenii pathovar nov. on the basis
      of morphological, physiological, biochemical and pathogenic characteristics.

PMID- 8546454
TI  - Taxonomy of Penicillium nalgiovense isolates from mould-fermented sausages.
AB  - A large number of Penicillium nalgiovense isolates from mould fermented sausages
      and the ex type culture were examined for characters of morphology, physiology
      and production of secondary metabolites. To separate biotypes within the P.
      nalgiovense species, the data obtained were evaluated using multivariate
      statistical methods. The macromorphological characters of the ex type culture and
      isolates from meat products appeared to be distinctive. The ex type culture is
      characterized by a brown reverse on both Czapek yeast extract and malt extract
      agar while the isolates from meat products have a yellow to orange reverse.
      Proteolytic and/or lipolytic activity was demonstrated by 75% of the examined
      cultures and all of them demonstrated ability to utilize lactate as sole carbon
      source. Growth on creatine sucrose agar was very inhibited and acid production
      was absent or very weak. TLC analysis showed production of three unknown
      secondary metabolites that constituted the characteristic profile. HPLC analysis
      showed production of only three known secondary metabolites; chrysogine (96%),
      nalgiolaxin and nalgiovensin (9%). The ex type culture produced nalgiolaxin and
      nalgiovensin but not chrysogine. The chemometric evaluation showed that P.
      nalgiovense isolates from meat products from a homogenous species, which can not
      be divided into biotypes. The only indication of grouping, beside a separation of
      the ex type culture, was related to the conidium colour (white, turquoise or grey
      green). The examined P. nalgiovense isolates showed some resemblance
      (morphologically and chemically) to P. chrysogenum.

PMID- 8546455
TI  - Sizing of the Rhodococcus sp. R312 genome by pulsed-field gel electrophoresis.
      Localization of genes involved in nitrile degradation.
AB  - The two restriction enzymes AsnI and DraI were found to produce DNA fragment
      sizes that could be used for mapping the Rhodococcus sp. R312 (formerly
      Brevibacterium sp. R312) genome by pulsed-field gel electrophoresis. AsnI
      produced 24 fragments (4 to 727 kb) and DraI yielded 15 fragments (8.5 to 2400
      kb). The fragment lengths in each digest were summed, indicating that the size of
      the chromosome ranged from 6.31 to 6.56 Mb, with a mean of 6.44 Mb. In addition,
      the wide-spectrum amidase gene (amiE) and the operon containing the enantiomer
      selective amidase gene (amdA) and the nitrile hydratase structural gene (nthA,
      nthB) were localized on the AsnI and DraI fragments.

PMID- 8546456
TI  - Ascomycetous yeast communities of marine invertebrates in a southeast Brazilian
      mangrove ecosystem.
AB  - The ascomycetous yeast communities associated with 3 bivalve mollusk, and 4 crab
      species were studied in the mangrove at Coroa Grande on Sepetiba Bay in Rio de
      Janeiro, Brazil. These were made up mostly of diverse but sparse and apparently
      allochtonous yeast populations. The striking exception was a prevalent population
      of the species Kluyveromyces aestuarii, which predominated the yeast communities
      of 2 detritus feeding crabs, Sesarma rectum and Uca spp., and the shipworm
      Neoteredo reynei. However, K. aestuarii was absent from the omnivorous crabs
      Aratus pisonii and Goniopsis cruentata, and the clam Anomalocardia brasiliana,
      and was rare in the clam Tagelus plebeius from mostly submerged more sandy
      sediments. Pichia membranaefaciens, Candida valida-like, Candida krusei, Candida
      sorbosa, Candida colliculosa-like, Candida famata-like, Kloeckera spp., Candida
      guilliermondii, Candida albicans, Candida silvae, Geotrichum spp., Rhodotorula
      spp., Cryptococcus spp., and the methylotrophic yeast Candida boidinii were
      frequently isolated. The 322 ascomycetous yeast cultures representing 252
      isolates from crabs and mollusks were classified as 40 species that fit standard
      descriptions, and 44 putative new species. The ascomycetous yeast communities of
      the mangrove ecosystem include many new biotypes that require better taxonomic
      definition.

PMID- 8546457
TI  - [Cancer and health economics].
AB  - Health economics on cancer medicine is a supportive tool of cancer care and is
      becoming one of the essential weapons against cancer. Its principal roles are to
      enhance the quality and efficacy and to secure the finance necessary to the
      cancer care. The economic aspects of cancer medicine and the methods of economic
      evaluation are overviewed with emphasis on cost-benefit, cost-effectiveness and
      cost-utility analysis. The operational and interpretational checkpoints are
      introduced, and the problems and prospects of the practical use of the methods on
      clinical settings such as cancer chemotherapy are discussed.

PMID- 8546451
TI  - Phylogenesis of fission yeasts. Contradictions surrounding the origin of a
      century old genus.
AB  - The phylogenesis of fungi is controversial due to their simple morphology and
      poor fossilization. Traditional classification supported by morphological studies
      and physiological traits placed the fission yeasts in one group with ascomycetous
      yeasts. The rRNA sequence comparisons, however, revealed an enormous evolutionary
      gap between Saccharomyces and Schizosaccharomyces. As shown in this review, the
      protein sequences also show a large gap which is almost as large as that
      separating Schizosaccharomyces from higher animals. Since the two yeasts share
      features (both cytological and molecular) in common which are also characteristic
      of ascomycetous fungi, their separation must have taken place later than the
      sequence differences may suggest. Possible reasons for the paradox are discussed.
      The sequence data also suggest a slower evolutionary rate in the
      Schizosaccharomyces lineage than in the Saccharomyces branch. In the fission
      yeast lineage two ramifications can be supposed. First S. japonicus (Hasegawaea
      japonica) branched off, then S. octosporus (Octosporomyces octosporus) separated
      from S. pombe.

PMID- 8546458
TI  - [A case of advanced esophageal cancer showing good partial response by
      combination therapy of low dose 5-FU and low dose CDDP].
AB  - A 66-year-old man with a complaint of dysphagia was diagnosed as advanced
      esophageal cancer. Barium swallow examination of the esophagus showed a narrowing
      10 cm in length at Ei (type 3), and biopsy specimen from the lesion on endoscopic
      examination revealed adenosquamous carcinoma. Multiple lymph node metastasis were
      detected by CT scan. He was treated with a combination of low dose 5-fluorouracil
      (5-FU) and low dose cisplatin (CDDP). The regimen consisted of 5-FU (300
      mg/body/day continuous infusion) and CDDP (10 mg/body/day continuous infusion)
      for 3 weeks. After 2 courses of this regimen, his symptoms disappeared, and only
      mild irregularity of the esophageal wall remained on Barium swallow examination.
      The effect of the therapy was evaluated as a partial response. No side effect was
      observed. From this case, the possibility that CDDP is able to function as a
      biochemical modulator for 5-FU was suggested.

PMID- 8546459
TI  - [FAM as a palliative chemotherapy for gastric cancer with bone metastasis].
AB  - A 50-year-old male was admitted to our hospital with severe malaise and lumbar
      pain. He suffered from diffuse bone metastasis of gastric cancer (mod. tub.
      adenocarcinoma) and DIC. In order to palliate his severe bone pain and bleeding
      tendency, FAM (5-fluorouracil 600 mg/body day 1, 7, 29, 36; doxorubicin 40
      mg/body day 1, 29; and mitomycin C 12 mg/body day 1) combination chemotherapy was
      used. After administration of FAM therapy, bone pain and bleeding tendency due to
      DIC disappeared. For three months after initiation of chemotherapy, the patient's
      quality of life was maintained fairly well. Adverse reactions of FAM therapy were
      only appetite loss for several days. FAM therapy might be a useful regimen for
      palliation of bone pain and DIC due to diffuse bone metastasis of gastric cancer.

PMID- 8546460
TI  - [Three cases of uterine cervical adenocarcinoma successfully treated by
      neoadjuvant chemotherapy with continuous intra-arterial infusion (cisplatin, 5
      fluorouracil)].
AB  - Low-dose consecutive intra-arterial infusion therapy with cisplatin and 5
      fluorouracil as neoadjuvant chemotherapy was performed on 3 cases of cervical
      adenocarcinoma (two stage IIb and one stage IIIb). Ten-day infusion of cisplatin
      10 mg/day (one shot) and 5-fluorouracil 250 mg/day (continuous) into blood flow
      altered bilateral internal iliac arteries, was carried out as one course and 2
      times at intervals of 3 weeks. As a result, side effects were slight, and all of
      these 3 cases showed a tumor diminution rate of above 83.5%, making it possible
      to perform complete tumorectomy through radical hysterectomy. However, some
      postoperative additional treatment was thought to be necessary, considering that
      with the present method, the area under the curve of free Pt of cubital venous
      blood is 2.4 mg hr/l and that by the present method alone long-term survival
      cannot be expected in cervical adenocarcinoma.

PMID- 8546461
TI  - [Combination therapy with irinotecan and CBDCA for patients in terminal stage of
      ovarian carcinoma].
AB  - Combination chemotherapy with irinotecan and CBDCA was performed for two patients
      in the terminal stage of ovarian carcinoma. Every week, 75 mg.m-2 of irinotecan
      and 75-100 mg.m-2 of CBD CA were intravenously administered. Both patients showed
      a partial response. Diarrhea was not a characteristic side effect of irinotecan
      in this case. Dose limiting factors were leucopenia and thrombocytopenia.

PMID- 8546462
TI  - [A case of superior vena cava syndrome treated with combination radiation and CRE
      (CBDCA and VP-16) therapy].
AB  - Carboplatin and etoposide were reported to be excellent radiation sensitizers. We
      encountered a patient with SVC syndrome due to lung cancer who was successfully
      treated by combination carboplatin, etoposide and hyperfractionation
      radiotherapy. A 72-year-old man was admitted to our hospital because of
      remarkable face edema. Computed tomography revealed a huge lung tumor and
      compressed SVC due to tumor growth. Acute tumor regression was essential for this
      case. We performed combination chemotherapy and radiation. The regime consisted
      of CBDCA 300 mg (day 1 1 hr drip infusion) and etoposide 50 mg/day for 21 days by
      oral administration. Two daily fractionations of 1.4 Gy were delivered 5 days-a
      week, with a 4 h interval between fractions (total dose 49.8 Gy). Complete
      response of huge tumor was attained in this case. The major side effect
      associated with the therapy was myelosuppression. The patient's quality of life
      has been remarkably improved with this therapy.

PMID- 8546463
TI  - [Mechanism of photodynamic therapy].
AB  - Mechanism of Photodynamic therapy and diagnosis has been discussed in terms of
      photophysical and photochemical properties. Also, the peak power dependence of
      laser on PDT effects has been examined.

PMID- 8546464
TI  - [Dynamics of photosensitizer in the cell].
AB  - 1) Mono-L-aspartyl chlorin e6 is a photosensitizer with a molecular weight of
      799.7 in which the double bond porphyrin ring has been reduced and an aspartic
      acid is attached to the propionic group at the carbon of the tetrapyrole ring via
      a peptide linkage. 2) The absorption spectrum of mono-L-aspartyl chlorin e6 is
      characterized by a Soret band at 398 nm and four Q bands located at 502, 530,
      620, and 654 nm in PBS solution at pH 7.4. However, when it bound to serum
      albumin at ratios of more than 1:1 absorption peaks showed a red shift at 6 nm in
      the PBS solution. 3) Erythrocytes in the blood containing serum albumin and the
      same concentration of mono-L-aspartyl chlorin e6 were not lysed with the diode
      laser irradiation. 4) The concentration of mono-L-aspartyl chlorin e6 in
      mitochondria fraction of normal tissue decreased from 2 hours after intravenous
      injection. However, the concentration of mono-L-aspartyl chlorin e6 in
      mitochondria fraction of tumor increased during 4 hours after injection and then
      gradually decreased.

PMID- 8546465
TI  - [Photodynamic therapy of centrally located early-stage lung cancer].
AB  - Photodynamic therapy (PDT) with photofrin II and excimer dye laser has an
      excellent effect on patients (pts) with centrally located early-stage lung cancer
      with a limited tumor length of 1 cm or less and a clearly visible tumor margin.
      Further, to expand the therapeutic area of PDT to these early-stage lung cancers,
      it is necessary to exploit more powerful laser equipment and more sensitive
      sensitizers. Also, it is essential in the decision to treat early-stage lung
      cancer to evaluate whether PDT can be used as an effective alternative therapy to
      surgery in patients with operable centrally located early-stage lung cancer.
      Finally, it is an important issue for the treatment of centrally located early
      stage lung cancer to determine which therapeutic modalities have to be selected
      as the initial choice in endoscopic therapy.

PMID- 8546466
TI  - [Photodynamic therapy for multiple primary lung cancer].
AB  - In recent years, multiple primary lung cancers have been reported with greater
      frequency, partly as a result of technologic advances in the detection of lung
      cancer and therapeutic achievements in its management. As for the treatment of
      multiple primary lung cancer, operative excision is usually difficult for all
      lesions due to problems of pulmonary function. PDT is a good therapeutic modality
      in the treatment of multiple primary lung cancer, especially central type lung
      cancer, for preservation of lung function. Since 1980, 27 patients of multiple
      primary lung cancers have been treated with PDT at Tokyo Medical College.
      Fourteen of these 27 patients were synchronous with the rest, metachronous. Seven
      of 27 patients with multiple tumors had early-stage lesions and were treated with
      endoscopic PDT alone. In other 20 cases, PDT was used to treat accessible early
      stage foci although operative excision was required for advanced lesions. Mean
      survival after PDT, alone or in combination with surgery, was 52 months (range, 5
      to 162 months) and 16 patients remain alive to date. PDT is useful in extending
      the therapeutic options for, and improving the prognosis of patients with,
      multiple primary bronchogenic carcinomas.

PMID- 8546467
TI  - [Photodynamic therapy for esophageal cancer].
AB  - Evaluation of resected cases of esophageal superficial cancer have shown that
      lymph node metastasis was absent, and radical local treatment would be possible
      for m1 and m2 cancer. However, the depth of cancer invasion is difficult to
      diagnose before treatment. Endoscopic mucosal resection (EMR) is useful for not
      only treating but also diagnosing cancer. Therefore, EMR is recommended as the
      treatment of choice for m1 or m2 lesions. On the other hand, treatment of
      esophageal superficial cancer by PDT is effective even for deep sm cancers. In
      particular, the use of excimer dye laser increases light transmittance, there by
      improving the treatment results for sm cancer. EMR was not effective for treating
      sm cancer or diagnosing the depth of its invasion. In sm cancer, since lymph node
      metastasis is observed in 30-50% of the cases, local treatment cannot be radical.
      Therefore, PDT is best indicated as a local treatment for sm cancer that cannot
      be treated by operation. Local healing after PDT prevents dysphagia caused by
      stenosis due to cancer, which may allow medical management at home.

PMID- 8546468
TI  - [Photodynamic therapy for gastric cancer].
AB  - In this article, we first present our clinical data on PDT for the treatment of
      gastric cancer and make a comparison between a continuous wave laser and a pulsed
      laser. The reasons for PDT failure in certain cases are also discussed. In the
      fifteen years from 1981 to 1995, we have treated a total of 76 gastric cancer
      lesions (73 cases), which was consist of 69 early gastric cancer lesions (66
      cases) and seven advanced gastric cancer lesions (seven cases) by PDT. From 1981
      to 1990, we used an argon dye laser (ADL, Models 171-08 and 375-03, Spectra
      Physics, Mountain View, Calif., US) as an excitation light source for PDT with
      HpD (Photofrin I), DHE (Photofrin II) or PHE (freeze-dried Photofrin II). From
      analysis of the results in terms of the depth of cancer invasion in these 44
      lesions (41 cases), the rate of cure for mucosal carcinomas was 57% (13/23), that
      of submucosal carcinomas was 53% (10/19), and that of carcinomas invading more
      than the muscularis propria was 0% (0/2). These data can be interpreted to
      indicate that the ADL laser beam could not penetrate and supply sufficient energy
      to activate HpD not only in the submoucosal layer but also in the mucosal layer.
      In 1990, therefore, we investigated an excimer dye laser (EDL, Hamamatsu
      Photonics, Hamamatsu, Japan), because its pulsed beam with extremely high peak
      power was expected to be more efficient at exciting HpD than continuous wave
      lasers such as ADL and high frequency pulsed lasers such as cooper vapor dye
      laser (Cu VDL). From 1990 to 1995, twenty-seven early gastric cancer lesions (27
      cases) and five advanced gastric cancer lesions (five cases) were treated by PDT
      with EDL and PHE. Of these 32 lesions, the rate of cure for mucosal carcinomas
      was 100% (15/15), that of submucosal carcinomas was 75% (9/12), and that of
      carcinomas invading more than the muscularis propria was 20% (1/5). For the
      purpose of determining how much energy was required for a complete cure in early
      gastric cancer, and to compare the efficacy of ADL and EDL, the relation between
      the response (cure or no cure) and irradiated energy intensity (dose: J/cm 2) was
      evaluated by the depth of cancer invasion and kind of laser used in PDT. A
      smaller EDL dose was more effective than ADL in terms of photodynamic action.

PMID- 8546469
TI  - [Photodynamic therapy (PDT) for early cervical cancer].
AB  - The incidence of carcinoma in situ (CIS) and dysplasia of the uterine cervix has
      been increasing among young women in recent years. Most of these patients want to
      preserve their fertility. Also, to accommodate high-risk patients with
      complications, elderly patients, and those who refuse surgery, we perform PDT as
      a method to preserve fertility. The technique required for PDT is relatively
      simple, and can be performed without anesthesia, since it causes no pain or
      bleeding. PDT, with the use of Excimer Dye Laser (EDL), a type of low pulse
      laser, has a considerably higher degree of tissue penetration, even compared to
      PDT using Argon Dye Laser (ADL). Also, PDT using EDL can manage glandular
      involvement of CIN, and its special feature of selective destruction of malignant
      cells with almost no effect on normal tissues is noteworthy. Beginning in 1995,
      PDT using YAG-OPO Laser with a variable laser wavelength has been performed. PDT
      is performed 48 hours after intravenous injection of 1.5 mg/kg to 2 mg/kg
      photosensitizer Porfimer sodium (PHE) when the difference in density of PHE
      becomes greatest between malignant cells and normal tissue. The most advanced
      features of our method compared to conventional radiation which uses cut fiber
      are: First, by using colposcope with an optical path for the laser, it is
      possible to show a 10 mm circular spot at the focus of observation. With this
      method, cervical lesions can be observed and checked while receiving stable and
      precise photoradiation by using colposcope through direct observation. Second,
      for cervical canal treatment, by using a cervical probe to administer
      photoradiation in the forward direction in the cervical canal and to the side
      walls, 70% of the laser light is scattered to the side walls, so that all of the
      cervical canal can be radiated. Also, the cervical canal probe used to administer
      photoradiation, by inserting 2 cm to 3 cm depending on the conditions of the
      cervical canal and withdrawing the probe 1 mm, can be performed precisely and
      promptly by using the cervical probe manipulator feature of the colposcope. At
      the present time, studies using the PDT method have been conducted on 56 patients
      (39 CIS and 17 dysplasia patients). Out of these 56 patients, there were 54 CR
      (96.4%), only one NC, and one PR with very limited remnants but most of the
      lesions had disappeared. The NC was highly suspected to be invasive carcinoma and
      the PR was CIS. In the CIS case, some remnant was evident at the end of the
      cervical canal, and PDT was administered again. After this treatment, it became
      CR. This was 10 months ago, and no abnormal condition has been reported since.
      The first CR case was reported 6 years ago among the 56 cases studied, and no
      recurrence has been observed to date. Five patients became pregnant after the
      treatment. Four had normal deliveries and one had a cesarean section. PDT's side
      effect is similar to symptoms of sunburn such as minor skin irritation due to
      sensitive reaction to sunlight. Normally, it can be relieved by applying carmine
      lotion, and even cases that required treatment were cured completely within a few
      days after applying steroid ointment. Before hospitalization, if the patient gets
      a sunburn from being outside, the sensitive reaction to laser light is almost
      nonexistent. Thus, we advise patients to get some exposure to the sun before
      being hospitalized. Also, in cases where strict shading time is observed, side
      effects are not apparent at all, and no abnormal findings are recognized in the
      blood and urine due to using PHE. With almost no side effects, bleeding or pain,
      and with certain improvements in administration methods, a better choice of
      photosensitizer which would shorten the shading time, PDT is considered to be the
      best therapy for treating CIS and dysplasia while preserving fertility.

PMID- 8546470
TI  - [Concurrent high-dose thoracic irradiation plus daily low-dose cisplatin and
      vindesine in locally advanced unresectable stage III non-small cell lung cancer].
AB  - Patients with unresectable non small-cell lung cancer were treated to evaluate
      the toxicity and efficacy of high-dose thoracic irradiation (RT) combined with
      concurrent daily cisplatin plus vindesine. Fourteen evaluable patients with
      unresectable stage III non small-cell lung cancer treated with continuous-course
      RT (70 Gy in 35 fractions of 2 Gy once daily) and concurrent daily intravenous
      cisplatin (6 mg/m2) plus vindesine (3 mg/m2 on day 1 and day 8). The objective
      response rate was 86%, and two patients achieved a radiographic complete
      response. Leukocytopenia was the severe toxicity, but there were no episodes of
      discontinuation of treatment. Only one patient had grade 3 acute radiation
      esophagitis. Ten patients experienced late radiation pneumonitis and nine of
      those had grade 1 or grade 2. There was only one life-threatening case of
      toxicity (grade 5 pneumonitis). We concluded that the regimen of high-dose
      thoracic RT combined with concurrent daily cisplatin plus vindesine obtained a
      high response rate. Further testing on late toxicities and survival time is
      required.

PMID- 8546471
TI  - [Study of serum CDDP concentrations in patients with advanced or recurrent adeno
      or squamous cell carcinoma under combination chemotherapy of 5-FU (CIV) and low
      dose CDDP (IV)].
AB  - The combination chemotherapy of 5-FU (CIV) and low-dose CDDP (IV) was applied to
      15 patients with advanced or recurrent adeno-or squamous cell carcinoma.
      Schedules for treatment were as follows: A: 5FU 320 mg/m2/day for 28 days with 7
      mg CDDP/m2/day for 5 days/weekx4. B: 5FU 320 mg/m2/day for 28 days with 3.5 mg
      CDDP/m2/day for 5 days/weekx4, C: after B, 7 mg CDDP/m2/day/every 3 or 4 days.
      Serum CDDP concentrations were measured by flameless atomic absorption
      spectrophotometry. In all patients, a tendency to accumulation of total CDDP was
      observed. No severe side effects (> or = grade 3) were observed in patients given
      B therapy. We previously reported that there was no significant difference
      between A and B therapy in anti-tumor effects. The peak total CDDP concentrations
      were 1000 or more than 1000 ng/ml in A therapy, and 500 to 1000 ng/ml in B (with
      the exception of a case) therapy. These results demonstrated that B therapy could
      maintain the anti-tumor effect and decrease the severity and frequency of side
      effects, suggesting that the optimal serum concentration of total CDDP might be
      between 500 and 1000 ng/ml.

PMID- 8546472
TI  - [Evaluation of preoperative chemotherapy for colorectal cancer].
AB  - Patients who underwent curative resection for colorectal cancer between January
      1987 and June 1989 were divided into two groups, to assess the usefulness of
      preoperative chemotherapy (400 mg UFT therapy daily for 10 days more) and to
      analyze changes in the proliferative activity of tumor cells. Fifty-five cases
      were included in the study. Thirty-three had received no preoperative
      chemotherapy (Group A), and 22 had received the preoperative chemotherapy (group
      B). The five-year cumulative survival rate was 81.1% for group A and 90.2% for
      Group B. The proportion of patients with no recurrence was 75.7% in Group A and
      85.7% in Group B. Both parameters thus tended to be better in patients who had
      received preoperative chemotherapy. When PCNA labeling before UFT therapy was
      compared with that after UFT therapy in 13 cases, the PCNA labeling rate
      decreased after UFT therapy in 9 (69%) of the 13 cases. These results suggest
      that preoperative chemotherapy using UFT is useful in treating colorectal cancer,
      and that the proliferative activity of colorectal cancer can sometimes be reduced
      by such preoperative adjuvant therapy.

PMID- 8546473
TI  - [Determination of 5-FU tissue concentrations after oral UFT administration in
      tumors of the head and neck].
AB  - We determined the 5-FU concentrations in the tumor tissue, normal tissue
      surrounding the tumor, metastatic lymph nodes, normal lymph nodes, and serum
      after oral UFT administration to 26 patients with primary squamous cell carcinoma
      in the head and neck. The 5-FU concentration was mean 0.20 +/- 0.13 micrograms/g
      in the tumor tissue and mean 0.14 +/- 0.08 micrograms/g in the metastatic lymph
      nodes. The 5-FU concentrations in the tumor tissue and metastatic lymph nodes
      were significantly higher than in the corresponding normal tissue surrounding the
      tumor and normal lymph nodes. In addition, the 5-FU concentration was
      significantly higher in the tumor tissue than in the metastatic lymph nodes. No
      significant differences were observed in the 5-FU concentration according to the
      sites of the primary tumor. However, the difference in the 5-FU concentration
      between the tumor and normal tissues was smaller in tongue cancer than in
      pharyngeal cancer.

PMID- 8546474
TI  - [History of photodynamic therapy--past, present and future].
AB  - Photodynamic therapy is achieved by a photodynamic reaction which is induced by
      excitation of photosensitizer exposed to light. This phenomenon was first
      reported by Raab et al in 1990. In 1960 Lipson et al reported hematoporphyrin
      derivative (HpD) by treating hematoporphyrin chloride with hydrochloric acid and
      sulfuric acid. The development of HpD established the basis of today's
      photodynamic therapy (PDT). Dougherty reported the treatment of skin tumors by
      PDT first with an argon dye laser in 1978. The author and his colleagues began
      basic studies of this treatment using HpD supplied by Dougherty and argon dye
      laser in canine lung cancer in 1978. These studies confirmed the effectiveness
      and safety of the method. Bronchofiberscopic PDT for early stage central type
      squamous cell carcinoma was performed by the authors in 1980 for the first time
      in the world and complete cure was obtained. Since then PDT has been attracted
      much attention. The photosensitizer and the laser with a specific wavelength are
      the key point of PDT. Photofrin, a porfimer sodium (Japan Lederle Co. Ltd.,
      Tokyo, Japan) and excimer dye laser (Hamamatsu Photonics Co. Ltd., Hamamatsu,
      Japan) obtained governmental approval for clinical use in Japan in 1994, which is
      equivalent to FDA approval in the US. This method is now used clinically in
      Canada for certain indications and the Netherlands. In the US it is only approved
      for compassionate use in cancer of the esophagus. A total of more than 3,000
      tumors in the various organs have been treated by PDT so far in 32 countries. The
      most frequently treated organ is the lung, with 808 cases. A phase II clinical
      study of PDT for early stage cancer cases of the lung, esophagus, stomach, cervix
      and urinary bladder was performed in 15 institutions from 1989 to early 1992. The
      results showed that PDT can successfully treat more than at least 50% of patients
      with early stage cancer cancer that would otherwise have to be treated by surgery
      and this means that PDT can contribute to their QOL. The cost effectiveness of
      PDT versus operation was estimated by the calculation based on QALY's (Quality
      Adjusted Life Year's saved) by Fujino of the Economics Department of Chuo
      University. According to this calculation PDT was estimated to be at least 30
      percent less than the cost of operation. PDT is indicated in cases with
      superficial localized early stage lung cancer as a curative treatment and as a
      palliative treatment for opening stenotic or obstructed bronchi due to tumor
      prior to the combination therapy with surgery. Recent studies on photodynamic
      therapy (PDT) began just two decades ago, therefore there are still a large
      number of unsolved problems. However PDT will have many applications in a wide
      range of fields from preclinical to clinical medical science. In lung cancer, the
      indications will be extended for early stage lung cancer and improvement of
      therapeutic results will be achieved by the development of new photosensitizers
      such as chlorin, pheophorbide, phthalocyanin, ALA, benzoporphyrin, etc which can
      be excited by longer wavelength and new lasers such as pulsed excimer dye, YAG
      OPO and diode lasers. Through these new developments the indications of this
      treatment for malignant will continue to expand.

PMID- 8546475
TI  - [Comparison of clinical effects between granisetron alone and combination of
      granisetron and methylprednisolone against the nausea and vomiting induced by
      CDDP chemotherapy--comparative study by the cross-over trial. University of
      Tsukuba Antiemetics Study Group].
AB  - A cross-over clinical trial was carried out to compare the antiemetic effect and
      safety between granisetron alone (40 micrograms/kg) and the combination of
      granisetron and methylprednisolone (MP: 10 mg/kg) in urological cancer patients
      treated with cisplatin. Forty-eight courses were given with granisetron alone and
      47 courses with both granisetron and MP. The antiemetic effect of nausea and
      vomiting was evaluated in the acute emetic phase. during the 24 hours following
      the CDDP administration, and in the delayed emetic phase, 2 to 7 days after the
      administration. Combination therapy of granisetron and MP demonstrated a greater
      antiemetic effect during the 72 hours following the CDDP administration than by
      granisetron alone. But there was no significant difference in antiemetic effect
      between combination therapy and granisetron alone after the 3rd day. Combination
      therapy also demonstrated more efficacy in complete antiemetic effect, with no
      emesis and less than moderate nausea, than by granisetron alone. Both treatments
      showed no side effects and were safe.

PMID- 8546477
TI  - [Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate
      and reduced glutathione) on adriamycin (doxorubicin)-induced toxicity and
      microsomal lipid peroxidation in mice].
AB  - The protective effects of the biological membrane stabilizing drugs, coenzyme Q10
      (CoQ), dextran sulfate (DS) and reduced glutathione (GSH), on doxorubicin
      (adriamycin, ADM)-induced toxicity and microsomal lipid peroxidation were studied
      in mice. The mice administered ADM with combined treatment of CoQ, DS or GSH
      showed a significantly longer survival time than the ADM control group (which
      were injected with 15 mg/kg of ADM twice). The optimum protective doses of these
      drugs against ADM-induced toxicity were 10 mg/kg/day (p.o.) for CoQ, 100
      mg/kg/day (s.c.) for DS and 100 mg/kg/day (i.p.) for GSH. The survival times of
      the mice (expressed as a percent of the treated group per control group) were
      224.1% for CoQ, 220.7% for DS and 213.7% for GSH. The groups treated with these
      drugs showed a significant decrease in mouse liver and heart microsomal lipid
      peroxidation in comparison to that of the ADM control group. These results
      suggest that the heart microsomal lipid peroxidation levels may be one of the
      indications of ADM-induced cardiac toxicity. These drugs tested in the present
      study may stabilize the heart microsomal membrane lipid or may improve the
      myocardiac mitochondrial functions over those in ADM-treated mouse.

PMID- 8546476
TI  - [Clinical evaluation of granisetron hydrochloride against nausea and vomiting
      induced by anticancer drugs for gynecological malignant tumors].
AB  - We, in the Department of Obstetrics and Gynecology, Kansai Medical College,
      conducted an evaluation of the usefulness and safety of granisetron hydrochloride
      used for nausea and vomiting due to chemotherapy in patients with gynecological
      malignant tumors, with an additional study of the efficacy of different regimens.
      The subjects were 9 patients in whom 16 courses of CAP therapy were given (group
      A) and 13 patients in whom 24 courses of CAP therapy were given (group B).
      Granisetron hydrochloride 3 mg/body was administered by intravenous drip in the
      two groups before chemotherapy. Clinical symptoms of nausea, vomiting, and
      anorexia were observed for 2 days after anticancer drugs were administered in
      order to evaluate its efficacy. The percentage of patients who responded as
      "effective" or better was 90.0%. In different regimens, the efficacy was 93.8% in
      group A and 87.5% in group B. These results indicated clinically high usefulness
      in both groups. No side effects related to granisetron hydrochloride were found
      in this study.

PMID- 8546478
TI  - [Two cases of long-term survival with hepatocellular carcinoma following
      targeting therapy with SMANCS/lipiodol].
AB  - We performed arterial infusion of SMANCS/Lipiodol in nineteen cases with
      hepatocellular carcinoma (HCC). We report two of these cases who survived for
      more than five years after the initial treatment. In case 1, HCC responded very
      well to the initial subsegmental infusion of SMANCS/Lipiodol with a prominent
      decrease in AFP level. In case 2, a 63-year-old male, repeated subsegmental
      infusion of SMANCS/Lipiodol for the local recurrence controlled the tumor well.
      In both cases, an approximately three-year period of complete remission passed
      until the tumor recurred. Arterial infusion of SMANCS/Lipiodol is expected to be
      a potent treatment for HCC. Its administration should be subsegmental, if
      possible, and should be repeated for local recurrence with a careful follow-up
      study.

PMID- 8546479
TI  - Neonatal curettage of giant congenital melanocytic nevi.

PMID- 8546480
TI  - Staphylococcal enterotoxin B applied on intact normal and intact atopic skin
      induces dermatitis.
AB  - BACKGROUND AND DESIGN: Colonization of inflammatory skin diseases with
      Staphylococcus aureus is a frequent phenomenon and may cause exacerbation of the
      skin disease. Staphylococcus aureus strains present on atopic dermatitis are
      capable of releasing staphylococcal enterotoxins, a group of superantigens that
      are very potent T-cell activators. To determine whether the superantigen
      staphylococcal enterotoxin B can induce inflammation when applied on the skin,
      staphylococcal enterotoxin B was applied with and without occlusion on the volar
      aspect of the skin on the forearm of 10 subjects without skin disease and six
      subjects with atopic dermatitis of minimal activity and no eczema on the volar
      aspect of the skin on their forearm. The main outcome measures were clinical
      rating; determination of the increase of the thickness of the skin-fold; and
      determination of skin blood flow. RESULTS: Clinically, staphylococcal enterotoxin
      B induced skin changes of erythema and induration in 10 of 10 healthy volunteer
      subjects and six of six subjects suffering from atopic dermatitis, while the
      vehicle induced clinically evident skin changes in only one of 10 healthy
      subjects and none of six subjects with atopic dermatitis. On day 3 after the
      application of an occluded patch containing 10 micrograms/cm2 of staphylococcal
      enterotoxin B in the healthy subjects, the thickness of the skinfold increased
      0.47 +/- 0.49 mm (mean +/- SD) (n = 9; P < .02) relative to the increase in the
      thickness of the skinfold following application of the vehicle. The Doppler laser
      measured skin blood flow index had increased from 1.0 +/- 0.4 to 5.3 +/- 3.7
      (mean +/- SD) (n = 10; P < .002). On day 3 after the application of occluded
      patchs containing 10 micrograms/cm2 of staphylococcal enterotoxin B in the
      subjects suffering from atopic dermatitis, the increase in the thickness of the
      skinfold increased 0.20 +/- 0.24 mm (n = 6; P, not significant) relative to the
      increased thickness in the skinfold following application of the vehicle. The
      Doppler laser-measured skin blood flow index had increased from 1.1 +/- 0.4 to
      3.7 +/- 2.2 (n = 6, P, not significant). Three of six subjects suffering from
      atopic dermatitis experienced a flare of their disease in the elbow flexure
      ipsilaterally to where the staphylococcal enterotoxin B patch was applied.
      CONCLUSIONS: The superantigen staphylococcal enterotoxin B applied on intact skin
      from both normal subjects and patients with atopic dermatitis induces an
      inflammatory reaction. This finding suggests that superantigens released from S
      aureus present on the skin in inflammatory skin diseases may exacerbate and
      sustain the inflammation.

PMID- 8546482
TI  - Increased serum concentration of the soluble interleukin-2 receptor in cutaneous
      T-cell lymphoma. Clinical and prognostic implications.
AB  - BACKGROUND AND DESIGN: The serum concentration of soluble alpha-chain receptor
      for interleukin-2 (sIL-2R) was determined in 101 patients with cutaneous T-cell
      lymphoma (CTCL). RESULTS: The serum concentration of sIL-2R correlates positively
      with CTCL tumor burden as determined by several clinical parameters (ie, clinical
      subtype of disease, extent of skin involvement, T rating, and stage), by serum
      lactate dehydrogenase concentration, and by Sezary cell counts in erythrodermic
      disease. The median value of sIL-2R in erythrodermic CTCL was more than threefold
      higher than that of classic mycosis fungoides (MF). The proportion of patients
      with elevated sIL-2R concentration (> 1000 U/mL) also increased in CTCL in a
      similar fashion according to the clinical type of disease (MF patch phase, 15%;
      MF plaque phase, 33%; MF tumor phase, 47%; and erythrodermic variants, 90%).
      However, no correlation was found between sIL-2R serum concentration and
      expression of membrane-bound IL-2R alpha chain (CD25) on lymphoid cells in skin
      lesions and peripheral blood. Significantly, multivariate analysis of various
      prognostic factors demonstrated that in erythrodermic CTCL, sIL-2R serum
      concentration correlated best with survival and was a better predictor of
      prognosis than stage, Sezary cell counts, or lactate dehydrogenase values.
      CONCLUSIONS: These findings document the usefulness of the measurement of the sIL
      2R serum concentration to determine tumor burden and prognosis in patients with
      CTCL.

PMID- 8546481
TI  - Antifungal pulse therapy for onychomycosis. A pharmacokinetic and pharmacodynamic
      investigation of monthly cycles of 1-week pulse therapy with itraconazole.
AB  - BACKGROUND AND DESIGN: In the treatment of onychomycosis, oral therapies have
      generally been given as a continuous-dosing regimen. For example, the suggested
      dose of itraconazole for the treatment of onychomycosis has thus far been 200
      mg/d for 3 months. Based on the advances in our understanding of the
      pharmacokinetics of itraconazole, we investigated the efficacy and nail kinetics
      of intermittent pulse-dosing therapy with oral itraconazole in patients who were
      suffering from onychomycosis. Fifty patients with confirmed onychomycosis of the
      toenails, predominantly Trichophyton rubrum, were recruited and randomly assigned
      to three (n = 25) or four (n = 25) pulses of 1-week itraconazole therapy (200 mg
      twice daily for each month). Clinical and mycological evaluation of the infected
      toenails, and determination of the drug levels in the distal nail ends of the
      fingernails and toenails, were performed at the end of each month up to month 6
      and then every 2 months up to 1 year. RESULTS: In the three-pulse treatment
      group, the mean concentration of itraconazole in the distal ends of the toenails
      ranged from 67 (month 1) to 471 (month 6) ng/g, and in the distal ends of the
      fingernails, it ranged from 103 (month 1) to 424 (month 6) ng/g. At month 11, the
      drug was still present in the distal ends of the toenails at an average
      concentration of 186 ng/g. The highest individual concentrations of 1064 and 1166
      ng/g were reached at month 6 for toenails and fingernails, respectively. At end
      point follow-up, toenails in 84% of the patients were clinically cured with a
      negative potassium hydroxide preparation and culture in 72% and 80% of the
      patients, respectively. In the four-pulse treatment group, the mean concentration
      of itraconazole in the distal ends of the toenails ranged from 32 (month 1) to
      623 (month 8) ng/g, and in the distal ends of the fingernails, it ranged from 42
      (month 1) to 380 (month 6) ng/g. The highest individual concentrations of 1549
      and 946 ng/g were reached at month 7 for toenails and at month 9 for fingernails,
      respectively. At month 12, the drug was still present in the distal ends of the
      toenails at an average concentration of 196 ng/g. At end-point follow-up,
      toenails in 76% of the patients were clinically cured with a negative potassium
      hydroxide preparation and culture in 72% and 80% of the patients, respectively.
      There were no significant intergroup differences between the three- and four
      pulse treatment groups for the primary efficacy parameters. The drug was well
      tolerated with no significant side effects in either patient group. CONCLUSIONS:
      Following pulse therapy with itraconazole (400 mg/d given for 1 week each month
      for 3 to 4 months), the drug has been detected in the distal ends of nails after
      the first pulse, and it has reached therapeutic concentrations with further
      therapy. After stopping the last pulse, the drug remains in the nail plate at
      levels above 300 ng/g for several months. Clinical cure rates between 76% and 84%
      and negative mycological examination findings between 72% and 80%, respectively,
      were observed in toenail onychomycosis. The data suggest that pulse therapy with
      itraconazole is an effective and safe treatment option for onychomycosis.

PMID- 8546483
TI  - Infraorbital crease, ethnic group, and atopic dermatitis.
AB  - BACKGROUND AND DESIGN: The usefulness of a prominent infraorbital skin crease as
      a marker of atopic dermatitis (AD) was examined in 160 consecutive children aged
      3 to 11 years in a population setting of a primary school in London, England.
      Infraorbital crease was recorded by two trained observers according to a strict
      protocol, and AD was determined by an independent dermatologist who was blinded
      to the study design. RESULTS: A prominent infraorbital crease was present in only
      four (27%) of 15 children with AD, compared with 49 (34%) of 145 children who did
      not have AD (P = .80). A prominent crease was a common finding in black children,
      even in the absence of AD, affecting 49% (34/69) of normal black children and 25%
      (11/44) of white children (P = .02). Interobserver agreement for the presence of
      infraorbital crease was low, with a kappa value of 0.38 (95% confidence interval,
      0.23 to 0.53). CONCLUSIONS: While infraorbital crease may be of some use in
      diagnosing individual cases of AD in a hospital setting, it may be less useful in
      population-based studies because of its poor validity and repeatability. Studies
      that still use this sign as an indication of allergy need to take ethnic group
      differences into account.

PMID- 8546484
TI  - Recurrent toxin-mediated perineal erythema.
AB  - BACKGROUND: Important new diseases due to bacterial toxins functioning as
      superantigens have been described with increasing frequency within recent years.
      Toxic shock syndrome, recalcitrant erythematous desquamating disorder,
      streptococcal toxic shock-like syndrome, and, most recently, mucocutaneous lymph
      node syndrome (Kawasaki disease) have been etiologically linked with certain
      staphylococcal and streptococcal toxins. We describe two patients with a novel
      clinical presentation of toxin-mediated disease, which shares certain clinical
      features with mucocutaneous lymph node syndrome. OBSERVATIONS: Two otherwise
      healthy young male adults developed recurrent erysipelaslike perineal erythema,
      which regularly erupted within 1 to 2 days of the onset of acute pharyngitis.
      Accompanying signs included mucosal changes and acral erythema with desquamation.
      Throat cultures obtained during the acute episodes yielded toxin-producing
      Staphylococcus aureus from one patient and toxin-producing Streptococcus pyogenes
      from the other. CONCLUSION: The recurrent nature, age predilection, and clinical
      presentation suggest that our patients display a unique clinical syndrome due to
      toxin-producing bacteria.

PMID- 8546485
TI  - Arcanobacterium haemolyticum pharyngitis and exanthem. Three case reports and
      literature review.
AB  - BACKGROUND: Arcanobacterium haemolyticum is a bacterial pharyngeal pathogen that
      infects adolescents and young adults, frequently causing an exanthem that may
      mimic a viral exanthem, toxic erythema, or drug eruption. To our knowledge, the
      cutaneous manifestations of A haemolyticum infection have not previously been
      reported in the dermatologic literature. OBSERVATIONS: The severity of this
      infection can range from mild pharyngitis to a diphtheria-like illness and even
      septicemia. We report three cases that demonstrate the spectrum of manifestations
      of this disease, including an unusual case with acral distribution of the
      associated exanthem. CONCLUSIONS: Arcanobacterium haemolyticum infection should
      be considered in the differential diagnosis when evaluating a young adult with an
      exanthem. Antibiotic treatment is reliably efficacious, but the throat swab must
      be specifically cultured on 5% human blood agar in order to make the diagnosis.

PMID- 8546486
TI  - Group A streptococcal infections. An old adversary reemerging with new tricks?

PMID- 8546487
TI  - Detection of mycobacterial DNA in the skin. Etiologic insights and diagnostic
      perspectives.
AB  - BACKGROUND: Tuberculosis may be as old as mankind and continues to be a serious
      medical problem today. Cutaneous tuberculosis shows considerable morphological
      variability, and it is included in the differential diagnosis of many other skin
      disorders. It is especially difficult to distinguish skin tuberculosis from other
      granulomatous processes of the skin. Therefore, reliable laboratory tests are
      needed to confirm or rule out the diagnosis. However, the diagnostic
      identification of Mycobacterium tuberculosis and related organisms has remained
      difficult using conventional laboratory tests (ie, microscopy and culture).
      OBSERVATIONS: The diagnostic usefulness of molecular techniques, especially the
      polymerase chain reaction (PCR), in skin tuberculosis is reviewed, and the
      technical issues of PCR in general are discussed, with special regard to the
      analysis of mycobacterial DNA in skin specimens. The PCR has been successfully
      applied to detect DNA from M tuberculosis in lupus vulgaris and several other
      forms of skin tuberculosis. It has also been used to identify mycobacterial DNA
      in certain forms of tuberculids, thereby supporting the long- and often-debated
      tuberculous origin of these skin disorders. Investigations of the presence of
      mycobacterial DNA in cutaneous sarcoidosis have not lent support to a general
      role for mycobacteria in sarcoidosis. CONCLUSIONS: Polymerase chain reaction
      based detection of M tuberculosis DNA in skin samples may extend and improve the
      diagnostic panel for cutaneous tuberculosis, if the technique is prudently and
      properly used. Furthermore, PCR provides exciting opportunities to gain further
      insight into the pathogenesis of cutaneous tuberculosis and other granulomatous
      skin diseases.

PMID- 8546488
TI  - Acute onset of bilateral hemorrhagic leg lesions. Pneumococcal cellulitis.

PMID- 8546489
TI  - Persistent perineal ulcerations. Erosive herpes simplex.

PMID- 8546490
TI  - Generalized rash in a Dominican immigrant. Borderline leprosy (Hansen's disease)
      with type 1 upgrading (ie, reversal) reaction.

PMID- 8546491
TI  - A slow growing lesion on the face. Lupus vulgaris.

PMID- 8546492
TI  - Psoralen plus UV-A-associated skin cancer: a likely role for human papillomavirus
      type 16?

PMID- 8546493
TI  - Hepatitis C virus infection and porphyria cutanea tarda in Australasia.

PMID- 8546494
TI  - Instrumentation for epiluminescence microscopy: the gap between research and
      practice.

PMID- 8546495
TI  - Mycobacterium tuberculosis DNA in papulonecrotic tuberculid.

PMID- 8546496
TI  - Failure of interferon alfa and isotretinoin combination therapy in the nevoid
      basal cell carcinoma syndrome.

PMID- 8546497
TI  - Helicobacter pylori antibodies in patients with psoriasis.

PMID- 8546498
TI  - Keratoacanthomas and skin neoplasms associated with suramin therapy.

PMID- 8546499
TI  - Late effects of phenylketonuria.

PMID- 8546500
TI  - Stepfamilies and children's adjustment.

PMID- 8546501
TI  - Maternal HIV infection, drug use, and growth of uninfected children in their
      first 3 years.
AB  - OBJECTIVE: To determine the separate effects of maternal HIV infection and drug
      use during pregnancy on growth of uninfected children in their first 3 years.
      DESIGN: Retrospective analysis of measurements from health visitor records made
      during routine child health surveillance at 6 weeks, 10 months, and 3 years of
      age. Multilevel analysis allowed for between-infant variation in fitted growth
      lines, and adjustment for other factors. Growth was described in terms of an
      intercept (z score at term) and growth slopes (change in z score per year) up to,
      and from, 4 months. SUBJECTS: 290 case babies delivered in Edinburgh hospitals to
      women who reported injection drug use by either themselves or their HIV infected
      partner, and 186 community controls. A total of 131 (45%) of the case babies were
      born to women who used drugs, predominantly opiates, during pregnancy and 93
      (32%) to HIV infected women. The eight infected children were excluded from
      analysis. MAIN OUTCOME MEASURES: Age and sex standardised z scores for height,
      weight, and body mass index. RESULTS: 459 (96%) of the 476 records for cases and
      controls were traced, yielding 1432 weight and 939 height measurements. Maternal
      HIV infection was not found to affect growth; at 3 years the estimated effect on
      weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for
      height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with
      lighter babies at 40 weeks followed by depressed growth in the first four months,
      these infants remaining just slightly smaller at 3 years with an estimated effect
      on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and 
      0.37 (-0.72 to -0.02) for height. CONCLUSIONS: Maternal HIV infection does not
      adversely affect growth in uninfected infants, and the effect of drug use during
      pregnancy is limited to small decrease in size at 3 years.

PMID- 8546502
TI  - What do mothers remember about the 'back to sleep' campaign?
AB  - A campaign was launched by the Department of Health late in 1991 to advise
      mothers how to reduce the risk of cot death. OBJECTIVE--To investigate whether
      mothers remember receiving this advice, their sources of information, and the
      advice they were given. SETTING--Questionnaires filled in by mothers of babies
      born in three maternity units in East Anglia. METHOD--150 mothers of full term
      babies born throughout 1992 were enrolled. All of them should have received the
      information. They were sent a questionnaire when their baby was 6 months old.
      RESULTS--399 (89%) questionnaires were analysable. Sources of information were:
      television, 72%; magazines, 59%; midwives, 55%; health visitors, 48%; and
      doctors, 11%. 23% said they received no advice from a health professional about
      reducing the risk of cot death. Doctors, who had all been informed by the
      Department of Health, were surprisingly poor at passing on the information.
      Advice on sleeping position was remembered by 72%, overheating by 60%, and
      smoking by 35%. Problems in following the advice were reported by only 5% of
      mothers. CONCLUSIONS--The media was most influential in spreading the new advice.
      Basic infant care advice is not the preserve of doctors.

PMID- 8546503
TI  - Immunisation and the sudden infant death syndrome. New Zealand Cot Death Study
      Group.
AB  - AIMS: To examine the relation between immunisation and the risk of sudden infant
      death syndrome (SIDS). METHODS: A large nationwide case-control study. Parental
      held records were used to measure immunisation status. RESULTS: Infants were at
      increased risk of SIDS if they had not received the 6 week, 3 month, and 5 month
      immunisations. After controlling for potential confounding variables, including
      those which measured health care use and infant illness, the relative risk of
      SIDS for infants not being immunised at 6 weeks was 2.1 (95% confidence interval
      = 1.2, 3.5). Four percent of cases died within four days of immunisation and 7.6%
      of control infants had been immunised within four days of the nominated date.
      There was a reduced chance of SIDS in the four days immediately following
      immunisation (OR = 0.5; 95% CI = 0.2 to 0.9). CONCLUSIONS: Immunisation does not
      increase the risk of SIDS and may even lower the risk.

PMID- 8546504
TI  - Apparent life threatening events and infant holding practices.
AB  - Two 4 week old infants are reported who suffered apparent life threatening events
      (ALTE) while being cradled in adult arms. The events, which could be reproduced
      under controlled circumstances, were not associated with any struggling by the
      infants. Alteration of infant holding practices in both cases resulted in
      cessation of the events. A case of cardiorespiratory arrest during breast feeding
      in an 8 week old infant that was unnoticed by her mother is also described. These
      cases suggest that certain infants may not respond normally to airway occlusion
      while being held or nursed, and show that careful study of the events surrounding
      ALTE may reveal contributing environmental factors. If ALTE occur around feeding
      time, observation of how caretakers place the infant during and after feeding may
      be informative.

PMID- 8546505
TI  - Calculation of the need for paediatric intensive care beds.
AB  - A study of paediatric intensive care usage and need was undertaken in the former
      English Northern region to define appropriate local provision in the light of
      apparently conflicting published evidence. It was hypothesised that daily bed
      need would follow a Poisson distribution. All admissions of children aged less
      than 15 years who required intensive care in the region were recorded
      retrospectively for the financial year 1993/4. The mean number of beds occupied
      was 11.7 per day, which is equivalent to 20.7 beds per million children per day.
      The distribution of numbers of beds used mirrored a Poisson distribution closely,
      and the predicted bed requirement to cover 95% of days in the year was in
      agreement with that observed. Review of recommendations for paediatric intensive
      care provision from other studies suggests that apparent differences arise
      largely from the effect of different sizes of population served, and that, when
      allowance is made for this, underlying rates of bed requirement are strikingly
      similar, with a mean of around 20 per million children per day. A formula is
      given for the application of this model to local populations.

PMID- 8546506
TI  - Antidiuretic hormone regulation in patients with primary nocturnal enuresis.
AB  - Treatment of primary nocturnal enuresis using DDAVP is based upon the hypothesis
      that antidiuretic hormone (ADH) secretion is insufficient at night. The known
      efficacy of the treatment on the one hand, and persisting doubts about its
      theoretical basis on the other, formed the background of the present study. Ten
      children (mean age 10.5 years) with primary nocturnal enuresis were compared with
      a corresponding control group of eight patients. Diurnal and nocturnal urine
      production, ADH secretion, and plasma osmolality were determined. No differences
      between the two groups were found for urine production, ADH levels during day and
      night, or plasma osmolality. However, in order to regulate plasma osmolality the
      enuretic children required a markedly greater output of ADH: 2.87 (95% confidence
      interval 0.091 to 40.35) pg/ml/mmol/kg v 0.56 (0.08 to 1.03) in the controls (p <
      0.01). The results are consistent with the established fact that ADH secretion is
      a function of plasma osmolality, and they contradict the hypothesis that urine
      production is increased at night in enuretics because of lower ADH secretion. The
      findings do not solve the uncertainties in the pathogenesis of enuresis but they
      suggest there might be a difference between enuretic children and controls at the
      ADH receptor level.

PMID- 8546507
TI  - Is microalbuminuria progressive?
AB  - In 1990, 81 children and adolescents with insulin dependent diabetes were studied
      for early signs of diabetic nephropathy. Nine patients were identified as having
      microalbuminuria (incipient nephropathy). These subjects were re-examined three
      years later. In five of these cases, the second examination revealed normal
      albumin excretion; in three of the four cases in whom microalbuminuria persisted,
      the rate of albumin excretion had decreased. The general improvement in albumin
      excretion rates in the initially microalbuminuric group could not be explained by
      improved glycaemic control nor interventional drug treatment. The lack of
      progression in this microalbuminuric group from the original prevalence study
      suggests that this method of identifying early nephropathy in childhood may not
      be valid or that the progression of incipient nephropathy in childhood is more
      irregular or slower than in later life.

PMID- 8546508
TI  - Cardiovascular autonomic dysfunction in diabetes mellitus.
AB  - The aim was to assess cardiovascular autonomic dysfunction in children and
      adolescents with diabetes mellitus. A total of 110 children and adolescents with
      type 1 (insulin dependent) diabetes (aged 6 to 18 years) and 130 non-diabetic
      controls were studied. Resting heart rate, heart rate variation to deep
      breathing, heart rate response to standing from a lying position, fall in
      systolic blood pressure on standing, and rise in diastolic blood pressure during
      sustained handgrip were measured. A reference range of results was obtained in
      the controls. Diabetic children had significantly increased resting heart rate
      [92.4 (SEM 2.5) v 84.2 (2.2) beats/min], decreased deep breathing heart rate
      variation [25.3 (0.9) v 32.8 (0.6) beats/min], and lower standing/lying heart
      rate ratio [1.23 (0.04) v 1.31 (0.03)] compared with controls. 46 diabetic
      children (42%) had at least one abnormal autonomic test result. Of these, 20
      (15%) had only one abnormal test and 26 (24%) had two or more abnormal tests.
      Using multiple logistic regression analysis, longer diabetes duration and worse
      long term metabolic control were independently predictive of cardiovascular
      autonomic dysfunction as the dependent variable [adjusted OR (95% CI): 2.9 (1.1
      5.9) and 3.3 (1.2-6.4), respectively]. Cardiovascular autonomic dysfunction is
      not rare in children with diabetes. Efforts should be made to maintain the best
      metabolic control to prevent or delay these complications.

PMID- 8546509
TI  - Lung function from infancy to school age in cystic fibrosis.
AB  - The aim was to investigate pulmonary mechanics in patients with cystic fibrosis
      during infancy and again in early childhood to see whether infant tests predicted
      status at school age. Plethysmographic measurements of thoracic gas volume and
      airways resistance were made in 29 patients at 6 months and again at 5 years 10
      months. Maximum flow at functional residual capacity was measured during infancy
      for comparison with maximum expiratory flow rates during childhood. While many
      patients had normal measurements during infancy, pulmonary function had
      deteriorated by school age. Thoracic gas volume at school age was significantly
      related to the values in infancy, but other measurements made during childhood
      were independent of infant values. The relations between measurements in infancy
      and early childhood described here provide a background against which the role of
      external factors on pulmonary function in young children with cystic fibrosis can
      be investigated.

PMID- 8546511
TI  - Choledochal cysts: lessons from a 20 year experience.
AB  - Cystic dilatation of the biliary tree is a rare congenital anomaly. To determine
      mode of presentation, diagnostic pitfalls, and long term outcome after surgery,
      78 children (57 girls, 21 boys) with choledochal cyst treated between 1974 and
      1994 were reviewed. Anatomical types were: Ic (n = 44), If (n = 28), IVa (n = 4),
      and V (n = 2); a common pancreaticobiliary channel was identified in 76%
      patients. Age at presentation ranged from 0-16 (median 2.2) years, six patients
      being diagnosed by prenatal ultrasonography. Of the 72 patients diagnosed
      postnatally, 50 (69%) presented with jaundice, associated with abdominal pain in
      25 or a palpable mass in three, 13 (18%) presented with pain alone, and two (3%)
      with a palpable mass. The classic triad of jaundice, pain, and a right
      hypochondrial mass was present in only four (6%). Four children presented acutely
      after spontaneous perforation of a choledochal cyst, two presented with ascites
      and one cyst was discovered incidentally. Plasma and/or biliary amylase values
      were raised in 30 of 31 patients investigated for abdominal pain; seven had
      evidence of pancreatitis at operation. In 35 of 67 (52%) patients referred
      without previous surgery, symptoms had been present for more than one month, and
      in 14 of them for more than one year, before diagnosis. Delayed referral was due
      to misdiagnosis as hepatitis (n = 12), incomplete investigation of abdominal pain
      (n = 6), and failure to note the significance of ultrasonographic findings (n =
      10). Two patients referred late died from liver failure. Of the 76 patients with
      type I or IV cysts, 59 underwent radical cyst excision and hepaticojejunostomy as
      a primary procedure and 10 as a secondary operation after previously unsuccessful
      surgery. Sixteen patients have been lost to follow up but most of the remainder
      are well after a mean period of 4.1 (0.1-13) years. Choledochal cysts are often
      misdiagnosed, but prognosis is excellent if radical excision is performed.

PMID- 8546512
TI  - Radiological assessment of constipation.
AB  - A scoring system for faecal loading was constructed by two experienced observers
      using the abdominal radiographs of 20 children. Four other observers
      independently graded the radiographs using this system and there was a high
      degree of agreement between all six observers (p < 0.001), suggesting that
      radiological assessment of constipation can be standardised.

PMID- 8546513
TI  - Radiological evidence of constipation in urinary tract infection.
AB  - Little objective evidence has been published to support the claim that
      constipation is an important contributory factor in recurrent urinary tract
      infection (UTI) in childhood. Using a radiological scoring system, two observers
      assessed faecal loading from abdominal radiographs of children with proved UTIs.
      There was a significant increase in the degree of faecal loading in children with
      UTI when compared with controls (r = 0.237). This difference was mainly accounted
      for by girls with recurrent (greater than five) UTIs. This study confirms an
      association between recurrent UTI and faecal loading. Further studies are needed
      to establish if there is a causal relationship and benefits from treatment.

PMID- 8546510
TI  - Bone and collagen turnover during treatment with inhaled dry powder budesonide
      and beclomethasone dipropionate.
AB  - OBJECTIVES: To assess bone and collagen turnover in asthmatic children treated
      with dry powder budesonide from the Turbuhaler and dry powder beclomethasone
      dipropionate from the Diskhaler in a dose of 800 micrograms/day. SUBJECTS:
      Thirteen prepubertal children with asthma. DESIGN: Open crossover study with two
      treatment periods and treatment free run-in and wash-out periods. All periods
      were of two weeks' duration. At day 14 in each period blood samples were taken
      for assessment of serum osteocalcin, the carboxyterminal propeptide of type I
      collagen (PICP), and the aminoterminal propeptide of type III collagen (PIIINP).
      At the same time urine was collected for assessment of creatinine corrected
      pyridinoline (uPYR/cr) and deoxypyridinoline (udPYR/cr) crosslinks. RESULTS:
      Osteocalcin concentrations were not influenced by any of the treatments. During
      budesonide treatment mean (SEM) PICP was reduced by 18% (8%) (p = 0.03), PIIINP
      by 24% (3%) (p = 0.0002), uPYR/cr by 16% (6%) (p = 0.03), and udPYR/cr by 21%
      (13%) (p = 0.12). During treatment with beclomethasone dipropionate mean (SEM)
      PICP was reduced by 20% (6%) (p = 0.01), PIIINP by 36% (3%) (p = 0.0002), uPYR/cr
      by 18% (4%) (p = 0.004), and udPYR by 13% (5%) (p = 0.02). The suppressive effect
      of beclomethasone dipropionate on PIIINP was more marked than that of budesonide
      (p = 0.001). CONCLUSION: Treatment with dry powder budesonide and beclomethasone
      dipropionate 800 micrograms/day is associated with suppression of bone and
      collagen turnover. The suppression seems to be more marked during treatment with
      beclomethasone dipropionate. Long term effects and effects of lower doses of
      budesonide and beclomethasone dipropionate on bone and collagen markers needs
      further study.

PMID- 8546514
TI  - Abrupt aggravation of atrioventricular block and syncope in hypertrophic
      cardiomyopathy.
AB  - A 10 year old girl with hypertrophic cardiomyopathy (HCM) developed high grade
      atrioventricular (A-V) block unexpectedly, which instantly led to syncope; she
      required a permanent pacemaker. High grade A-V block, a rare complication of HCM,
      relates closely to syncope or sudden death in this disease and if progressive the
      use of cardiac pacing should be considered without delay.

PMID- 8546515
TI  - Response to drugs and diet in a compound heterozygote for familial
      hypercholesterolaemia.
AB  - A boy with a total plasma cholesterol concentration of 20.9 mmol/l which fell
      significantly with a low fat diet, cholestyramine and simvastatin, was shown to
      have two different mutations in the low density lipoprotein receptor gene,
      demonstrating that some patients with homozygous familial hypercholesterolaemia
      show a good lipid lowering response to treatment.

PMID- 8546516
TI  - Child health statistical review, 1995.

PMID- 8546517
TI  - Effects of nicotine on bacterial toxins associated with cot death.
AB  - Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx
      of cases of sudden infant death syndrome (SIDS) have a lethal effect when
      injected into chick embryos. If the toxins are progressively diluted the lethal
      effect disappears, but certain combinations of toxins show synergy so that if
      sublethal doses are mixed a highly lethal effect is produced. In this paper it is
      shown that nicotine at very low concentrations (less than that produced in man by
      0.05 cigarettes) potentiates the lethal action of certain SIDS associated
      bacterial toxins and markedly potentiates the lethal action of synergistic
      combinations of bacterial toxins. These results could explain, at least in part,
      why parental smoking increases the risk of SIDS. They also provide further
      support for the common bacterial toxin hypothesis of cot death.

PMID- 8546518
TI  - The EEG and neuroimaging in the management of the epilepsies.

PMID- 8546519
TI  - The place of the EEG and imaging in the management of seizures.

PMID- 8546520
TI  - The new BPA classification.

PMID- 8546521
TI  - Diphtheria: are we ready for it?

PMID- 8546523
TI  - Prostaglandin endoperoxide synthetase isoenzymes: the clinical relevance of
      selective inhibition.

PMID- 8546522
TI  - Understanding inorganic pyrophosphate metabolism: toward prevention of calcium
      pyrophosphate dihydrate crystal deposition.

PMID- 8546524
TI  - Early rheumatoid arthritis: time to aim for remission?

PMID- 8546525
TI  - Specific drugs for a complex disease: can there be a magic bullet against
      rheumatoid arthritis?
AB  - The complexity of RA challenges our search for a better understanding of the
      interconnected networks. Early treatment will certainly avoid some of the
      problems presented by the complexity of the disease, and combined treatments seem
      advantageous for advanced disease. The complexity of overt RA will probably not
      allow a single agent to exert superior efficacy. Unless a treatable infectious
      cause is identified, a magic bullet, though theoretically possible, might not
      exist in reality, in particular if the disease is advanced.

PMID- 8546526
TI  - 'Arthritis' in Byzantium (AD 324-1453): unknown information from non-medical
      literary sources.
AB  - OBJECTIVE--To compile and analyse information contained in non-medical texts of
      the Byzantine historians and chroniclers concerning arthritis, and to clarify the
      first use of Colchicum autumnale in the treatment of gout by the fifth century
      physician, Jacob Psychristus. CONCLUSIONS--This material gives an indication of
      the problem of arthritis and, in particular, a disease resembling gout that
      tyrannised a great number of the population in the Byzantine Empire (AD 324
      1453). Contemporary historians and chroniclers maintain that the main causes of
      gout ('podagra') were the over-consumption of alcoholic drinks and food. Most
      relevant texts include anxiety and heredity among the aetiological factors of the
      disease. The incidence of this group of diseases among the Byzantine Emperors (it
      is certain that 14 of a total of 86 had a form of arthritis) and other officials
      of the State indicates that these diseases were a possible factor in certain
      political and military difficulties of the Empire.

PMID- 8546527
TI  - Shoulder disorders in general practice: incidence, patient characteristics, and
      management.
AB  - OBJECTIVES: To study the incidence and management of intrinsic shoulder disorders
      in Dutch general practice, and to evaluate which patient characteristics are
      associated with specific diagnostic categories. METHODS: In 11 general practices
      (35,150 registered patients) all consultations concerning shoulder complaints
      were registered during a period of one year. Patients with an intrinsic shoulder
      disorder who had not consulted their general practitioner for the complaint
      during the preceding year (incident cases) were asked to participate in an
      observational study. Participants completed a questionnaire regarding the nature
      and severity of their complaints. The general practitioners recorded data on
      diagnosis and therapy. RESULTS: The cumulative incidence of shoulder complaints
      in general practice was estimated to be 11.2/1000 patients/year (95% confidence
      limits 10.1 to 12.3). Rotator cuff tendinitis was the most frequently recorded
      disorder (29%). There were 349 incident cases enrolled in the observational
      study. Patient characteristics showed small variations between different
      diagnostic categories. Age, duration of symptoms, precipitating cause and
      restriction of movement seemed to be discriminating factors. Twenty two percent
      of all participants received injections during the first consultation; most (85%)
      were diagnosed as having bursitis. The majority of patients with tendinitis (53%)
      were referred for physiotherapy. CONCLUSION: With respect to diagnosis and
      treatment, the practitioners generally appeared to follow the guidelines issued
      by the Dutch College of General Practitioners. Although the patient
      characteristics of specific disorders showed some similarities with the clinical
      pictures described in the literature, further research is required to demonstrate
      whether the proposed syndromes indeed constitute separate disorders with a
      different underlying pathology, requiring different treatment strategies.

PMID- 8546528
TI  - Hip osteoarthritis and dysplasia in Chinese men.
AB  - OBJECTIVE: To estimate the prevalence of hip osteoarthritis (OA hip) and hip
      dysplasia in a sample of Hong Kong men who were unselected with respect to hip
      symptoms. METHODS: The postmicturition films of 999 men aged 60-75 years,
      consecutive attenders for intravenous urography between 1987 and 1990 at a
      regional hospital, were reviewed. OA hip was diagnosed as the occurrence of two
      or more features of OA using a modified version of the Kellgren and Lawrence
      scale, or a minimal joint space of 1.5 mm or less. Hip dysplasia was defined as a
      centre-edge angle of less than 25 degrees, or an acetabular depth of less than 9
      mm. The results were compared with British data obtained by similar methods.
      RESULTS: In the Hong Kong sample, the proportion of men with two or more features
      of osteoarthritis in at least one hip was about 50% that of the men in the
      British study (5.4% and 11.0%, respectively). Severe joint space narrowing (of
      1.5 mm or less) occurred in 0.7% of the hips in Hong Kong men, compared with 2%
      in the British men. The proportion of hips with centre-edge angles less than 25
      degrees was 4.5% in Hong Kong, compared with 3.6% in Britain, and the prevalence
      of shallow acetabular depth was greater in Chinese (14.5%) than in the British
      (2.1%). Radiographic measures of hip dysplasia were not associated with minimal
      joint space. CONCLUSIONS: Our results have confirmed the lower prevalence of
      radiographic hip osteoarthritis in Hong Kong men compared with British men.
      However, acetabular dysplasia was as prevalent among Chinese men as in the
      British sample. This is evidence against the hypothesis that variations in the
      frequency of hip osteoarthritis are caused by differences in the occurrence of
      hip dysplasia.

PMID- 8546529
TI  - Determination of interstitial collagenase (MMP-1) in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: To investigate whether interstitial collagenase (MMP-1) concentration
      in synovial fluid can be useful as a marker for disease activity in rheumatoid
      arthritis (RA), to determine the main route by which collagenase degrades the
      matrix of articular cartilage, and to investigate if an imbalance between
      metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) is
      responsible for the activity of MMPs in RA. METHODS: Collagenase concentrations
      were measured in synovial fluid and paired serum samples using a specific
      sandwich enzyme linked immunosorbent assay. Collagenase activities were also
      assayed in synovial fluid samples. Synovial tissues obtained from the same
      patient were examined by immunohistochemical staining and the numbers of cells
      expressing collagenase were counted. RESULTS: Collagenase concentrations in
      synovial fluid did not correlate with C reactive protein and collagenase levels
      in serum, but did correlate positively with the degree of synovial inflammation,
      and increased with increasing numbers of cells identified as expressing
      collagenase in synovial tissue. Collagenase activities did not correlate with
      TIMP-1 concentrations, but did correlate strongly with the ratios of collagenase
      concentration to TIMP-1 (r = 0.73). CONCLUSION: The collagenase concentration in
      synovial fluid cannot be used as a marker for systemic disease activity, but can
      be used as a marker for the degree of synovial inflammation in the joint from
      which the sample is aspirated. In advanced RA, most of the collagenase is
      probably produced in synovial lining cells and released into synovial fluid,
      where it degrades the matrix of articular cartilage. An imbalance between MMP and
      TIMP may be of importance in the degradation of extracellular matrix of articular
      cartilage in RA.

PMID- 8546530
TI  - IL-1 has no direct role in the IGF-1 non-responsive state during experimentally
      induced arthritis in mouse knee joints.
AB  - OBJECTIVE: To investigate the involvement of interleukin-1 (IL-1) in the
      induction or maintenance of the insulin-like growth factor 1 (IGF-1) non
      responsive state of chondrocytes during experimental arthritis in mouse knee
      joints. METHODS: To characterise IGF-1 nonresponsiveness during arthritis, we
      measured chondrocyte proteoglycan (PG) synthesis by assaying incorporation of 35S
      sulphate into mouse patellar cartilage, obtained from knee joints with
      experimentally induced arthritis and normal knee joints, cultured with IGF-1. We
      investigated whether suppressive mediators produced by the arthritic synovium or
      chondrocytes abolished the IGF-1 stimulation of normal cartilage, and used IL-1
      primed cartilage to mimic the arthritic in vivo state. Specific inflammatory
      mediators responsible for the maintenance of the suppressed IGF-1 response were
      sought. We measured IGF-1 responsiveness in normal and arthritic patellae
      cultured with antibodies against tumour necrosis factor (TNF) or IL-1 alpha/beta,
      with IL-1 receptor antagonist (IL-1ra), and with several inhibitors of
      proteolytic enzymes or reactive oxygen species, and analysed the role of IL-1 in
      the development of IGF-1 non-responsiveness by studying IGF-1 responses in
      cartilage treated with IL-1 antibodies in vivo, at the onset of arthritis.
      RESULTS: Mediators from the surrounding tissue of both normal and arthritic
      cartilage suppressed chondrocyte IGF-1 responses. Priming the cartilage with IL-1
      did not directly induce IGF-1 non-responsiveness, but enhanced the ability of
      suppressive mediators from synovium or chondrocytes to downregulate the IGF-1
      responsive state. IL-1ra, IL-1 alpha/beta antibody, TNF antibody, or the
      inhibitors tested did not markedly improve the disturbed IGF-1 response, but
      treatment with anti-IL-1 at the onset of arthritis prevented the development of
      IGF-1 non-responsiveness. CONCLUSION: IL-1 alone does not induce IGF-1 non
      responsiveness and is not critical in the maintenance of this phenomenon.
      However, IL-1 does appear to be an important cofactor in the generation of the
      IGF-1 non-responsive state.

PMID- 8546531
TI  - HLA class II genes associated with anticentromere antibody in Japanese patients
      with systemic sclerosis (scleroderma).
AB  - OBJECTIVE: To define further HLA class II gene associations with anticentromere
      antibody (ACA), a major serum antinuclear antibody in patients with systemic
      sclerosis (SSc). METHODS: HLA class II genes were determined using polymerase
      chain reaction/restriction fragment length polymorphisms in 94 Japanese patients
      with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control
      subjects. RESULTS: Frequency of DQB1*0501 was increased in ACA positive SSc
      patients compared with ACA negative SSc patients (36% versus 13%; p = 0.02, odds
      ratio = 4.0, 95% confidence interval 1.1 to 13.9), but the association of ACA
      with a polar amino acid at position 26 in the DQB1 beta 1 domain, which was
      demonstrated in white North Americans, was not observed in Japanese. The
      DRB1*0101, *0405, and *1302 alleles were associated with high ACA titres, whereas
      DRB1*1502 was associated with low ACA titres and a low frequency of centromere
      protein C (CENP-C) reactivity. CONCLUSIONS: These results suggest that the ACA
      response is associated with multiple HLA class II genes and that ACA positive SSc
      patients are heterogeneous in terms of immunogenetic background.

PMID- 8546532
TI  - Predominance of HLA-DRB1*0405 in Korean patients with rheumatoid arthritis.
AB  - OBJECTIVE: To identify the association of HLA-DR4 subtypes with rheumatoid
      arthritis (RA) in Koreans. METHODS: Ninety five patients with RA and 118 normal
      control subjects were examined for HLA-DR antigens by serology. Subtypes of HLA
      DR4 were determined by allele specific oligonucleotide typing. RESULTS: The
      phenotype frequency of HLA-DR4 in RA patients was significantly greater than that
      in controls (60.0% versus 31.4%, odds ratio (OR) 3.28, 95% confidence interval
      (CI) 1.79 to 6.02 (p < 0.001)), but HLA-DR6 was decreased in RA patients (15.8%
      versus 32.2%, OR 0.39, 95% CI 0.19 to 0.81 (p < 0.001)). When DR4 was excluded
      from analysis of patients and controls, the allele frequency of DR1 was
      significantly increased in the patients compared with controls (11.3% versus
      4.5%, OR 2.73, 95% CI 0.87 to 5.95 (p < 0.001)). Forty two of 57 DR4 positive
      patients (73.7%) possessed DRB1*0405, which was strongly associated with RA
      (44.2% of patients, versus 11.9% of controls: OR 5.88, 95% CI 2.81 to 12.47 (p <
      0.001)). DRB1*0403 was not found in the patients, but was present in 8.5% of
      controls. Examining the third hyper-variable region at position 70-74 in the
      DRB1*04 chain by oligotyping, we found that 52 of 57 DR4 positive patients
      (91.2%) carried one of the conserved amino acid sequences QRRAA or QKRAA, known
      to be the epitope conferring predisposition to RA. CONCLUSION: This study
      confirms that RA is strongly associated with DR4, especially with DRB1*0405, and
      that the presence of the inferred QRRAA sequence may be important in
      susceptibility to RA in Koreans.

PMID- 8546533
TI  - Factors associated with Pneumocystis carinii pneumonia in Wegener's
      granulomatosis.
AB  - OBJECTIVE: To determine the factors associated with the occurrence of
      Pneumocystis carinii pneumonia (PCP) in Wegener's granulomatosis (WG). METHODS:
      We retrospectively compared a group of 12 patients with WG and PCP (PCP group),
      with 32 WG patients without PCP followed over the same period in the same centres
      (control group). RESULTS: The mean delay of onset of PCP after the start of the
      immunosuppressive therapy was 127 (SD 128) days. Before treatment, the clinical
      and biological features of the two groups were similar, except for the mean
      lymphocyte count which was lower in the PCP group than in the control group
      (1060/mm3 v 1426/mm3; p = 0.04). During treatment, both groups were lymphopenic.
      There was a significant difference between the lowest absolute lymphocyte count
      in each group (244/mm3 in the PCP group v 738/mm3 in the control group; p =
      0.001). During the first three months of treatment, the lymphocyte count was less
      than 600/mm3 at least once in 10 of the 12 patients in the PCP group and in 11 of
      the 32 patients in the control group (p < 0.01). The mean cumulative dose of
      cyclophosphamide was greater in the PCP group than in the control group at the
      end of both the second (1.55 mg/kg/day v 0.99 mg/kg/day; p = 0.05) and the third
      (1.67 mg/kg/day v 0.97 mg/kg/day; p = 0.03) months. However, in multivariate
      analysis, the only two factors independently and significantly associated with
      the occurrence of PCP were the pretreatment lymphocyte count (p = 0.018) and the
      lymphocyte count three months after the start of the immunosuppressive treatment
      (p = 0.014). CONCLUSIONS: The severity of lymphocytopenia before and during
      immunosuppressive treatment is the factor best associated with PCP in WG.

PMID- 8546534
TI  - Immunohistochemical demonstration of fibronectin in the most superficial layer of
      normal rabbit articular cartilage.
AB  - OBJECTIVE: To locate fibronectin ultrastructurally in the most superficial layer
      of normal articular cartilage of rabbits, in order to clarify its role in joint
      physiology. METHODS: Articular cartilage was obtained from the femoral condyle of
      seven normal adult rabbits and prepared by a method that included tannic acid
      fixation. Polyclonal antibodies against rabbit fibronectin were used in an
      immunohistochemical electron microscopic study, without any enzymic digestion but
      with a pre-embedding method for the transmission electron microscopy. RESULTS:
      The cartilage surface was successfully preserved by tannic acid fixation. The
      most superficial layer in electron photomicrographs was approximately 200-300 nm
      thick, cell free, and appeared to have two parallel components: the more
      superficial lamina and the deeper lamina. Gold labelled fibronectin lined this
      layer in immunohistochemical electron photomicrographs. CONCLUSIONS: Fibronectin
      covering the surface of the articular cartilage may have a role in joint
      lubrication and protection of the cartilage by binding with the collagenous
      matrix and hyaluronic acid in synovial fluid. Chondroitin sulphates may act as a
      charge barrier in close relationship with the collagen fibrils in the deeper
      lamina. Significant alteration in these functions may be one of the first causal
      steps leading to destruction of the articular cartilage.

PMID- 8546535
TI  - Effects of the 5-hydroxytryptamine1A receptor agonists, 8-OH-DPAT, buspirone and
      flesinoxan, upon brain damage induced by transient global cerebral ischaemia in
      gerbils.
AB  - The effects of the 5-hydroxytryptamine1A agonists, 8-OH-DPAT, buspirone and
      flesinoxan, on the delayed hyperactivity and on the ensuing neuronal degeneration
      induced by transient global cerebral ischaemia, were studied. In normothermic,
      male Mongolian gerbils, subjected to 3 min bilateral carotid artery ligation, the
      locomotor activity was measured 1 day after ischaemia. The neuronal damage was
      quantified 7 days later using an image analysis system. Buspirone (3 and 10
      mg/kg, i.p.) and flesinoxan (1 and 3 mg/kg, i.p.), administered twice a day for 3
      days both in pre- and post-ischaemic conditions, failed to significantly protect
      the CA1 zone of the hippocampus against neuronal damage. In contrast, 8-OH-DPat
      (1 and 3 mg/kg, i.p.) significantly reduced the neuronal degeneration. All
      compounds abolished the hyperactivity but there was no correlation between this
      parameter and the extent of the reduction in neuronal damage. The ineffectiveness
      of buspirone and flesinoxan was not the result of too low a dose - as evidenced
      by the complete inhibition of hyperactivity with both compounds and by the
      appearance of a serotonin behavior syndrome with flesinoxan - but is possibly
      related to a partial agonist activity at the 5-hydroxytryptamine1A receptor, as
      reported for buspirone. Further studies are necessary to explain the differences
      between these agonists.

PMID- 8546536
TI  - Characterization of the biphasic blood pressure response to alpha-methyl-5
      hydroxytryptamine in anaesthetized rats.
AB  - The aim of the present study was to investigate the mechanism of the biphasic
      blood pressure response to the 5-hydroxytryptamine2 (5-HT2) receptor agonist,
      alpha-methyl-5-HT (alpha-Me-5-HT) in anaesthetized rats. In conscious rats, 5-HT
      (2.5-15 micrograms/kg, i.v.) produced typical triphasic blood pressure responses
      at the higher doses. In anaesthetized rats, 5-HT produced only hypotensive
      responses at all doses. In conscious rats, i.v. injections of alpha-Me-5-HT (5
      125 micrograms/kg) produced dose-dependent increases in mean arterial pressure
      with concomitant bradycardia. However, in inactin-anaesthetized rats, alpha-Me-5
      HT produced biphasic blood pressure responses consisting of an initial pressor
      response followed by a longer lasting depressor phase. In anaesthetized rats, the
      5-HT1A antagonist, spiroxatrine (1 mg/kg), and the 5-HT3 receptor antagonist,
      MDL72222 (0.3 mg/kg), selectively diminished the hypotensive phase without
      affecting the pressor phase. The 5-HT1/5-HT2 antagonist, methysergide (0.5
      mg/kg), and the selective 5-HT2 antagonist, ketanserin (50 micrograms/kg),
      completely abolished all responses to alpha-Me-5-HT. Pretreatment with the 5-HT
      selective uptake inhibitor, fluoxetine (1 mg/kg), produced a significant
      attenuation of the hypotensive response whilst enhancing the pressor response.
      Pretreatment with the 5-HT depletor, p-chlorophenylalanine (3 x 100 mg/kg/day),
      produced an attenuation of the hypotensive phase while the pressor response was
      augmented. The selective 5-HT2/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-
      amino-propane (5-200 micrograms/kg, i.v.), produced dose-dependent pressor
      responses in anaesthetized rats but no hypotensive responses were observed. The
      results show that the 5-HT2 agonist, alpha-Me-5-HT, produces a biphasic blood
      pressure response in anaesthetized rats which is not seen in conscious rats. The
      hypotensive response is due to a nonselective activation of 5-HT1 and 5-HT3
      receptors through release of 5-HT.

PMID- 8546537
TI  - Dose-response analysis of acute hypotensive and renal effects of atrial
      natriuretic peptide in the rat.
AB  - Acute treatments with synthetic atrial natriuretic peptides induce hypotension,
      in which several mechanisms, including renal effects, are involved. The
      implication of the renal vasculature and the excretory capacities in the
      hypotensive action of atrial natriuretic peptides are not ascertained as yet. To
      address this issue, the rapid time sequence of the acute effects of atrial
      natriuretic peptides upon renal blood flow, mean arterial pressure, heart rate,
      and salt and water excretion, as well as a dose-response analysis, were
      investigated in 38 anesthetized euvolemic rats. Doses varying from 0.25 to 2.50
      micrograms of atrial natriuretic peptide were injected i.v. in 30 sec. Each dose
      induced a brisk and transient increase in renal blood flow, which was maximal
      (13%) above 1 microgram of atrial natriuretic peptide. A small reduction in mean
      arterial pressure, timely related to renal vasodilation, occurred at first. It
      was followed by a second reduction in mean arterial pressure, which was
      concomitant to the maximal increases in diuresis and natriuresis. It persisted
      over a longer period of time. The maximal hypotensive effect (-15 mmHg) was
      observed above 1.5 micrograms of atrial natriuretic peptide. All effects were
      dose-dependent. There were no changes in heart rate. In conclusion, atrial
      natriuretic peptides transiently induced dose-dependent increases in renal blood
      flow and salt and water excretion, while the mean arterial pressure decreased
      stepwisely. The biphasic hypotensive effect was time-related to the renal
      vasodilator and diuretic effects, respectively.

PMID- 8546538
TI  - In vitro vasorelaxant effects of indolocarbazole and bis-indole protein kinase C
      inhibitors on rabbit renal arteries.
AB  - The effects of 12 compounds, structurally related to the indolocarbazole
      bacterial metabolite staurosporine, on caffeine-induced contractions in rabbit
      renal arteries were studied. Eight of these compounds are effective protein
      kinase C inhibitors, the others are inactive towards the enzyme. The results show
      a link between the protein kinase C inhibitory activity and the inhibition of
      vascular smooth muscle contraction. However, a strong inhibition of protein
      kinase C is required to observe the vasorelaxant effect.

PMID- 8546539
TI  - Cyclosporin A and Cremophor-EL augment renal vascular responses to various
      agonists and nerve stimulation.
AB  - The acute actions of cyclosporin A and its solvent Cremophor-EL on the rise of
      perfusion pressure induced by periarterial stimulation were studied in the rabbit
      isolated kidney. Thirty-second stimulations were used and the parameters were 1
      25 Hz, 5 msec duration, and 15 V. The responses to periarterial stimulation were
      frequency-dependent. Noradrenaline (0.01-20 microgram) induced similar effects
      when given into the renal artery. Clonidine (10(-7)M), added to the perfusion
      medium, inhibited the responses to periarterial stimulation without altering the
      effect of noradrenaline. Cyclosporin A (10(-7)-4 x 10(-5)M), added to the
      perfusion medium, potentiated the responses both to periarterial stimulation and
      exogenously given noradrenaline and restored the responses to clonidine (10(
      7)M). The effects of cyclosporin A and Cremophor-EL on the responses to various
      contractile agonists (potassium chloride, phenylephrine, serotonin and
      angiotensin II) were also studied in the rabbit isolated renal artery. The
      results suggest that cyclosporin A may exert a direct action on the vasculature
      rather than an action on the vascular adrenergic neurotransmission of the rabbit
      kidney.

PMID- 8546540
TI  - Arrhythmias in organophosphate poisoning: effect of atropine and bispyridinium
      oximes.
AB  - The effect of atropine and of the bispyridinium oximes, HI6 and HLo 7, on the
      electrocardiographic pattern was investigated in acutely nerve agent-poisoned
      guinea-pigs. The electrocardiographic, circulatory and respiratory parameters
      were recorded in female urethane-anaesthetized Pirbright-white guinea-pigs. After
      base line measurements, the animals received pyridostigmine (0.05 mumol/kg) and,
      30 min later, tabun (5xLD50), sarin (5xLD50), soman (5xLD50 or 10xLD50) or VX
      (10xLD50 or 20xLD50), followed by saline or atropine (10 mg/kg) or atropine plus
      HI 6 or or HLo 7 (30 mumol/kg) 2 minutes later. Nerve agent poisoning resulted in
      respiratory arrest within 2-3 minutes, followed by circulatory arrest a few
      minutes later in nontreated animals. Antidote treatment rapidly restored heart
      rate and mean arterial pressure and improved the respiratory function to various
      extent. The nerve agent injection caused a marked sinus bradycardia and a
      subsequent complete atrioventricular block within 1-2 minutes, followed by
      idioventricular rhythm. No ventricular tachyarrhythmias were observed in these
      groups just before death. Atropine and atropine plus oxime administration
      immediately restored sinus rhythm which persisted in animals with sufficient
      respiration > 50% of base line) throughout the observation period (60 minutes).
      In guinea-pigs with depressed respiratory function ( < 50%), intermittent ST-T
      wave alterations and second degree atrioventricular block were observed. In some
      cases, especially in tabun and soman (10xLD50) poisoning, sinus rhythm converted
      to deleterious ventricular tachycardia within 1 minute after treatment. These
      results suggest that atropine-containing antidote combinations may induce lethal
      arrhythmias in nerve agent poisoning, which may be of clinical importance during
      intravenous treatment of severe inhalative intoxications.

PMID- 8546541
TI  - Differential relevance of beta-adrenoceptor subtypes in modulating the rat brown
      adipocytes function.
AB  - The potencies and intrinsic activities on cyclic AMP accumulation and lipolysis
      of various selective beta 3-adrenoceptor agonists were studied in brown
      adipocytes and compared to those of the nonselective, (-)-isoprenaline, and
      conventional beta 1- (dobutamine) and beta 2-adrenoceptor (salbutamol) agonists.
      (-)-Isoprenaline, dobutamine and salbutamol were more potent stimulants of
      lipolysis than of cyclic AMP accumulation, while the selective beta 3
      adrenoceptor agonists had similar potencies for these two functions. Apparent pA2
      values of the selective beta 1-(CGP20712A) and beta 2-adrenoceptor (ICI118551)
      antagonist for inhibition of adenylyl cyclase stimulation by (-)-isoprenaline and
      the beta 3-adrenoceptor agonists, BRL37344, SR58611A, and ICI215001, indicated
      that (-)-isoprenaline can stimulate the enzyme through a relevant beta 1
      adrenergic component, while the other drugs activate the enzyme mainly by acting
      on the beta 3-adrenoceptors. On the contrary, antagonism of the lipolysis yielded
      apparent pA2 values for CGP20712A and ICI118551, suggesting that (-)
      isoprenaline, like all the beta 3-adrenoceptor agonists, stimulated the brown
      adipose tissue lipid metabolism mainly through an action on beta 3-adrenoceptors.

PMID- 8546542
TI  - Diazepam, adenosine analogues and calcium channel antagonists inhibit the
      contractile activity of the mouse urinary bladder.
AB  - The main neurotransmitter of the mouse urinary bladder is ATP, which is
      hydrolyzed to AMP and adenosine; the latter compound, in contrast to ATP, relaxes
      the smooth muscle. Diazepam also relaxes the urinary bladder and, since some
      peripheral and central effects of the benzodiazepines are thought to be induced
      by inhibition of adenosine uptake or by inhibiting calcium channels, the effects
      of diazepam, adenosine, R-phenylisopropyladenosine, cyclohexyladenosine, and of
      the calcium channel antagonists, diltiazem, verapamil and nifedipine, were
      studied on the contractile responses of the mouse isolated urinary bladder. The
      contractile responses of the bladder's smooth muscle were elicited by transmural
      stimulation and by application of ATP or acetylcholine. All drugs mentioned
      decreased the contractile responses of the bladder. The inhibitory effect of
      diazepam was similar to that induced by adenosine, R-phenylisopropyladenosine,
      cyclohexyladenosine, and nifedipine. 8-Phenyltheophylline, an adenosine receptor
      antagonist, did not decrease the relaxatory response of diazepam, which might
      exclude a P1 purinoceptor-mediated mechanism in the response studied. Diazepam
      did not significantly change the inhibitory effects of diltiazem and nifedipine
      on the contractile response to acetylcholine. The similar patterns of relaxant
      effects, exerted by diazepam, adenosine analogues and calcium channel
      antagonists, suggest the interference of benzodiazepine, and adenosine and its
      analogues on calcium channels of the urinary bladder smooth muscle. The inability
      of diazepam to further increase the effects of diltiazem and nifedipine on the
      responses to acetylcholine, reinforces the hypothesis that diazepam is acting
      through a common mechanism with calcium antagonists.

PMID- 8546543
TI  - Emerging infectious disease.

PMID- 8546544
TI  - Put prevention into practice. A systematic approach to the delivery of clinical
      preventive services.

PMID- 8546545
TI  - Cindy's death.

PMID- 8546546
TI  - Empathy revisited.

PMID- 8546547
TI  - The interface between research and the diagnosis of an emerging tick-borne
      disease, human ehrlichiosis due to Ehrlichia chaffeensis.
AB  - Two new ehrlichial species that cause human disease have recently been
      identified: Ehrlichia chaffeensis and the currently unnamed agent of human
      granulocytic ehrlichiosis. Our objective was to review data on the clinical
      presentation, laboratory and epidemiological findings, therapy, and diagnostic
      procedures of patients with human ehrlichiosis due to E chaffeensis. From 1986
      through 1994, 400 case patients were identified from 30 US states. Most patients
      had a nonspecific illness, characterized by fever and headache. Severe illness
      and death occurred, primarily in the elderly. Laboratory findings most commonly
      included leukopenia, thrombocytopenia, and elevated liver function test results.
      Antibody response was the basis for diagnosis, although polymerase chain reaction
      testing has been useful in research settings. Empirical treatment with
      tetracycline or its analogues should be begun as soon as possible after the onset
      of symptoms. Clinicians need to be alert for this illness when evaluating febrile
      patients whose history includes possible recent tick exposure.

PMID- 8546548
TI  - Congestive heart failure with normal left ventricular systolic function. Clinical
      approaches to the diagnosis and treatment of diastolic heart failure.
AB  - The syndrome of congestive heart failure with preserved left ventricular systolic
      function is common in clinical practice. The signs and symptoms of the disorder
      are similar to those of congestive heart failure with left ventricular systolic
      dysfunction, underscoring a need for routine evaluation of left and right
      ventricular systolic function in patients with congestive heart failure. The
      syndrome may be related to anatomic abnormalities that increase the resistance to
      ventricular filling, or to physiologic abnormalities of myocardial relaxation or
      compliance. Advancing age, often in association with hypertension, coronary
      artery disease, tachycardia, and atrial fibrillation, is commonly associated with
      the disorder. Randomized controlled clinical trials are needed to evaluate the
      efficacy of various therapeutic agents in reducing the risks associated with
      diastolic heart failure.

PMID- 8546549
TI  - Tuberculosis prophylaxis in the homeless. A trial to improve adherence to
      referral.
AB  - BACKGROUND: Adherence to tuberculosis evaluation is poor in a high-risk
      population such as the homeless. OBJECTIVE: To test two interventions aimed at
      improving adherence to tuberculosis evaluation and to identify predictors of
      adherence. METHODS: We conducted a randomized clinical trial in shelters and food
      lines in the inner city of San Francisco, Calif. We randomized 244 eligible
      subjects infected with tuberculosis to (1) peer health adviser (assistance by a
      peer [n = 83]), (2) monetary incentive ($5 payment [n = 82]), or (3) usual care
      (referral slips and bus tokens only [n = 79]). The primary outcome of the study
      was adherence to a first follow-up appointment at the tuberculosis clinic, where
      subjects were evaluated for active tuberculosis and the need for isoniazid
      prophylaxis. RESULTS: Of the subjects assigned to a monetary incentive, 69 (84%)
      completed their first follow-up appointment, compared with 62 subjects (75%)
      assigned to a peer health adviser and 42 subjects (53%) assigned to usual care.
      Adherence was higher in the monetary incentive and peer health adviser groups
      than in the usual care group (P < .001 and P = .004, respectively). Patients not
      using intravenous drugs and patients 50 years of age or older were more likely to
      adhere to a first follow-up appointment (odds ratios [95% confidence intervals],
      2.5 [1.3 to 5.0] and 3.3 [1.2 to 8.8], respectively). Among the 173 tuberculosis
      infected subjects who completed their appointment, isoniazid therapy was started
      for 72 individuals, and three cases of active tuberculosis were identified.
      CONCLUSION: A monetary incentive or a peer health adviser is effective in
      improving adherence to a first follow-up appointment in homeless individuals
      infected with tuberculosis. A monetary incentive appears to be superior.
      Intravenous drug users and young individuals are at high risk for poor adherence
      to referral.

PMID- 8546550
TI  - Effect of comprehensive intervention program on survival of patients with human
      immunodeficiency virus infection.
AB  - BACKGROUND: In October 1989, an early intervention program (EIP) for human
      immunodeficiency virus (HIV) infection was initiated in New Jersey to provide
      medical care and social services to the enrollees. OBJECTIVE: To assess the
      overall effect of the EIP on the survival of HIV-infected patients. METHODS:
      Patient information collected through June 30, 1993, was analyzed from the Jersey
      City Medical Center EIP clinic. Survival from enrollment to death was calculated
      for patients who received follow-up at the clinic (active) and for those who only
      had the enrollment visit (inactive). The data were matched with the New Jersey
      death certificate registry. RESULTS: Of 938 patients enrolled from October 1989
      to December 1991, 767 had T-cell subsets determined within 3 months of
      enrollment: 641 patients were active and 126 were inactive. At entry, inactive
      patients had a lower median CD4+ T-cell count and were more likely to be
      symptomatic than active patients. Among the 640 active and 125 inactive patients
      analyzed for survival (survivors > or = 2 months), there were 144 (22.5%) and 48
      (38.4%) deaths, respectively. Kaplan-Meier analysis indicated longer survival for
      active patients than for inactive patients (P < .001, Wilcoxon's test for
      homogeneity of strata); eg, survival probability at 2 years was 86% for active
      patients and 64% for inactive patients. Active patients also had longer survival
      than inactive patients when stratified by CD4+ T-cell levels or by clinical
      status. Only active and inactive patients with both CD4+ T-cell levels lower than
      0.20 x 10(9)/L (< 200/microL) and symptoms of HIV or acquired immunodeficiency
      syndrome had similar survival rates. Survival was not influenced by sex, race, or
      HIV transmission category. CONCLUSION: Participation in the EIP was associated
      with longer survival of HIV-infected patients.

PMID- 8546551
TI  - A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii
      prophylactic regimens.
AB  - BACKGROUND: Finding the optimal strategy for Pneumocystis carinii prophylaxis in
      patients with human immunodeficiency virus infection can be problematic. Several
      prophylactic regimens are available, but their relative efficacy and tolerance
      are not well understood. METHODS: A meta-analysis overviewed 35 randomized trials
      comparing different regimens for P carinii prophylaxis directly or with placebo.
      Analyses were based on intention-to-treat. On-treatment data were also analyzed
      when available. RESULTS: Regardless of dose, sulfamethoxazole-trimethoprim was
      almost universally effective for patients who tolerated it. The risk of
      discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by
      43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given
      three times a week instead of daily. For dapsone, among 100 patients given 100 mg
      daily instead of twice a week for 1 year (primary prophylaxis), seven fewer
      patients would develop P carinii pneumonia, but 17 more would have significant
      toxic reactions. Aerosolized pentamidine was well tolerated regardless of the
      dose used. Prophylaxis failures might be halved if the dose of aerosolized
      pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens
      prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on
      treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by
      intention-to-treat. No significant difference in mortality was demonstrated
      between different regimens. CONCLUSIONS: Sulfamethoxazole-trimethoprim is the
      superior regimen, and low doses could improve tolerance without losing
      effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects,
      but at the expense of some loss of efficacy. There are few data on the use of low
      dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine
      may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate
      for prevention of toxoplasmosis, and strategies that improve the tolerance of
      oral regimens may increase effectiveness in preventing toxoplasmosis.

PMID- 8546552
TI  - Lack of usefulness of radiographic screening for pulmonary disease in
      asymptomatic HIV-infected adults. Pulmonary Complications of HIV Infection Study
      Group.
AB  - OBJECTIVE: To determine the use of chest radiographs in the screening of
      asymptomatic adults infected with the human immunodeficiency virus (HIV).
      METHODS: A prospective, multicenter study of the pulmonary complications of HIV
      infection in a community-based cohort of persons with and without HIV infection.
      The subjects included 1065 HIV-seropositive subjects without the acquired
      immunodeficiency syndrome at the time of enrollment: 790 homosexual men, 226
      injection drug users, and 49 women with heterosexually acquired infection.
      Frontal and lateral chest radiographs were performed at 3-, 6-, and 12-month
      intervals, CD4 lymphocyte measurements at 3- and 6-month intervals, tuberculin
      and mumps skin tests at 12-month intervals, and medical histories and physical
      examinations at 3- and 6-month intervals. Pulmonary diagnoses that occurred
      within 2 months following each radiograph were analyzed and correlated with the
      radiographic results. RESULTS: Evaluable screening chest radiographs (5263) were
      performed in HIV-seropositive subjects while they were asymptomatic; of these,
      5140 (98%) were classified as normal and 123 (2%) as abnormal. A new pulmonary
      diagnosis was identified within 2 months following a screening radiograph in 55
      subjects. Only 11 of these subjects had abnormal radiographs; the sensitivity of
      the radiograph was 20%. The sensitivity was similarly low at baseline, within
      each transmission category, and in subjects whose CD4 lymphocyte counts were less
      than 0.2 x 10(9)/L (200/microL). The types of pulmonary diseases that occurred
      were similar in the subjects with normal and abnormal screening radiographs.
      CONCLUSION: Screening chest radiography in asymptomatic HIV-infected adults is
      unwarranted because the diagnostic yield is low.

PMID- 8546553
TI  - Determinants of nontraditional therapy use in patients with HIV infection. A
      prospective study.
AB  - BACKGROUND: The popularity and use of nontraditional therapies among patients
      with human immunodeficiency virus (HIV) infection has grown enormously. DESIGN: A
      prospective, longitudinal cohort study of 56 patients aged 23 through 68 years
      with HIV infection followed up at the HIV clinic at a university-affiliated
      Veterans Affairs Medical Center. OBJECTIVE: To assess the demographic and
      psychologic characteristics of patients who seek nontraditional remedies, and
      their impact on disease progression and mortality from HIV. METHODS: A
      standardized, self-administered questionnaire to assess the incidence and type of
      nontraditional therapies used by patients with HIV. Data on demographics, medical
      status, physical functioning (Karnofsky performance score), CD4 lymphocyte
      counts, depression (Beck Depression Inventory), coping (inventory of coping with
      illness scale), psychological and/or emotional stress (Profile of Mood States
      scores), and compliance with prescribed therapy were prospectively assessed on
      all patients at baseline and every 6 months. RESULTS: Thirty percent of patients
      reported using nontraditional therapies. Nontraditional therapy users were
      significantly older than patients who did not use such therapies (44 vs 38 years,
      P = .03); with 94% of patients who used nontraditional therapy being older than
      35 years compared with 56% of conventional therapy users (P = .005). Alternative
      therapy use did not correlate with race, education, HIV-risk group affiliation,
      duration of HIV seropositivity, stage of HIV disease, CD4 cell count, or
      Karnofsky performance scores. Nontraditional therapy users reported greater
      community-based acquired immunodeficiency syndrome group support (P = .06),
      greater perceived social support (P = .08), and significantly higher recreational
      or "street drugs" use (P = .02). Depression, adaptive coping, and emotional
      stress were not different between nontraditional and conventional therapy users;
      however, nontraditional therapy users were significantly more assertive (P =
      .04). On follow-up, CD4 cell count, HIV disease progression, physical
      functioning, or mortality were similar between the two groups. CONCLUSIONS:
      Recourse to nontraditional therapy is common among patients with HIV. Because of
      the possibility of untoward effects and potential adverse drug interactions
      associated with nontraditional therapy, HIV care givers should be aware of its
      use in their patients and take a history of nontraditional therapy first.
      Patients who choose nontraditional remedies do so not because they are depressed
      or emotionally disturbed, but rather because they seek greater control of the
      outcome of their disease. However, no beneficial effect on disease progression,
      CD4 cell count, or mortality was observed in these patients when compared with
      patients receiving only conventional medical therapy.

PMID- 8546554
TI  - Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda
      Kaposi's Sarcoma Study Group.
AB  - BACKGROUND: Endemic Kaposi's sarcoma (KS) is a clinically and epidemiologically
      distinct human immunodeficiency virus negative form of KS occurring in Africa.
      Kaposi's sarcoma is now the most frequently reported cancer in some areas of
      Africa. OBJECTIVE: To determine if a KS-associated herpesvirus (KSHV) is present
      in both endemic HIV-seronegative and HIV-seropositive KS lesions from African
      patients. METHODS: Paraffin-embedded tissue specimens from Ugandan patients with
      KS and non-KS tumor control patients attending a university-based oncology clinic
      were examined in a blinded case-control study. Tissue DNA specimens were examined
      for detectable KSHV genome by nested polymerase chain reaction performed at two
      independent laboratories. RESULTS: We identified KSHV in 17 (85%) of 20 KS tissue
      specimens from HIV-seronegative patients and 22 (92%) of 24 KS tissue specimens
      from HIV-infected persons. Kaposi's sarcoma lesions from four HIV-infected
      persons and four HIV-seronegative persons were positive for KSHV. Unlike previous
      studies in North America and Europe, three (14%) of 22 non-KS cancer control
      patients' tissue specimens were also positive for KSHV that resulted in an
      overall odds ratio of 49.2 (95% confidence interval, 9.1 to 335) for detecting
      KSHV in KS lesions from patients in Uganda. CONCLUSION: As in North America and
      Europe, KSHV infection is strongly associated with both HIV-seropositive and HIV
      seronegative KS in Africa. However, it is likely that infection with this virus
      is more highly prevalent in Uganda.

PMID- 8546555
TI  - Reactions following administration of influenza vaccine alone or with
      pneumococcal vaccine to the elderly.
AB  - BACKGROUND: Even though the efficacy of pneumococcal vaccine against invasive
      pneumococcal infections and other closely related infections has been
      established, its use in the United States is only one quarter of that of
      influenza vaccine. The simultaneous administration of the two vaccines could be
      expected to raise the coverage of pneumococcal vaccination to a considerable
      degree. There is a paucity of data regarding the reactions associated with the
      simultaneous administration of pneumococcal and influenza vaccines. METHODS: All
      persons aged 65 years or older living in 29 administrative districts in Northern
      Finland were offered influenza vaccine alone or influenza and pneumococcal
      vaccines. A total of 9336 persons (49.6% of the target population) accepted
      vaccination: 4581 persons born in odd years received influenza vaccine, and 4755
      persons born in even years received influenza and pneumococcal vaccines. Local
      reactions were recorded in a diary by vaccines on the day of vaccination and for
      4 days afterward according to the following scale: no reaction, mild reaction,
      strong reaction, and disabling reaction. The participants who felt feverish were
      asked to measure and record their temperature. Ninety-three percent of those
      vaccinated returned the diary. RESULTS: No serious reactions were observed. The
      incidence of local reactions was 284 per 1000 vaccinations in the influenza
      vaccinated group and 441 per 1000 vaccinations in the influenza-pneumococcal
      vaccinated group, a difference of 157 (95% confidence interval, 137 to 176), and
      that of fever (temperature, at least 37.5 degrees C) was 10 and 24 per 1000,
      respectively, for a difference of 14 (95% confidence interval, 9 to 19). The
      frequency of local reactions decreased with advancing age. CONCLUSION: Because
      the adverse reactions to the pneumococcal and influenza vaccines when given
      together were mild, we conclude that the simultaneous administration of the two
      vaccines to the elderly population, irrespective of age, is safe.

PMID- 8546556
TI  - Variability in the interpretation of screening mammograms by US radiologists.
      Findings from a national sample.
AB  - OBJECTIVE: To evaluate the effectiveness of screening mammography by estimating
      the variability in radiologists' ability to detect breast cancer within the US
      population of radiologists at mammography centers accredited by the American
      College of Radiology. METHODS: A two-way sample survey design was used as
      follows. Fifty mammography centers having an American College of Radiology
      accredited unit were randomly sampled from across the United States. One hundred
      eight radiologists from these centers gave blinded interpretation to the same set
      of 79 randomly selected screening mammograms. The mammograms were from women who
      had been screened at a large screening center. Before their sampling, these women
      had been stratified by their breast disease status, established either by biopsy
      or by 2-year follow-up. Rates of biopsy recommendations were summarized by the
      mean, median, minimum, maximum, and range of sensitivity and specificity. Overall
      cancer detection ability was summarized by similar statistics for receiver
      operating characteristic curve areas. Ninety-five percent lower confidence bounds
      on the ranges in accuracy measures were established by boo-strapping. RESULTS:
      There is a range of at least 40% among US radiologists in their screening
      sensitivity. There is a range of at least 45% in the rates at which women without
      breast cancer are recommended for biopsy. As indicated by receiver operating
      characteristic curve areas, the ability of radiologists to detect cancer
      mammograms varies by as much as 11%. CONCLUSIONS: Our findings indicate that
      there is wide variability in the accuracy of mammogram interpretation in the
      population of US radiologists. Current accreditation programs that certify the
      technical quality of radiographic equipment and images but not the accuracy of
      the interpretation given to mammograms may not be sufficient to help mammography
      fully realize its potential to reduce breast cancer mortality.

PMID- 8546557
TI  - Venous thrombosis and tight underwear.

PMID- 8546558
TI  - Cholesterol lowering and the risk of stroke.

PMID- 8546559
TI  - Cardiopulmonary resuscitation and survival.

PMID- 8546560
TI  - Desert Storm syndrome and immunization.

PMID- 8546561
TI  - [Reconstruction of the explosion site of a hand granade on an automobile seat].
AB  - A hand grenade exploded in a VW-Bus killing the female passenger. The paper
      describes how examination of damage to the material of the drivers seat, seat
      cushion and to a blanket was able to provide information which helped to
      reconstruct the effects of the explosion and to determine the position of the
      grenade at the moment of detonation.

PMID- 8546562
TI  - [A historical skull specimen in Leipheim with evidence of penetrating injury].
AB  - Report on a skull, which was found in a dredged pit together with 20 incomplete
      skeletons. There were two sharp-edged lesions without signs of regeneration,
      probable caused by a sharp object like a sword. Relics found at the scene led to
      the presumption, that the skull belonged to a victim of peasant's war, which
      happened in the early 16th century. Details referring to the mechanism of the
      injury are analyzed as well as the dating and the estimation of the subject's
      age.

PMID- 8546563
TI  - [Homicide or suicide? A contribution to the topic of insufficient investigation].
AB  - Two deaths by stab wounds are reported, which were first mistaken for suicide and
      discovered only on autopsy. The hypothesis "suicide", which was based only on the
      statements made by the women ascertained as the offenders later, was not
      questioned by the doctors doing the postmortem examination and was accepted
      without further investigation by the police officers first handling the cases.
      Moreover, in the second case the signs of the repeated impact of blunt force were
      overlooked in addition.

PMID- 8546564
TI  - [Homicidal versus suicidal penis amputation. A contribution to the problem of
      missing and conflicting stains].
AB  - Report of the case of a 78-year-old man who was found dead with complete
      amputation of the penis and parts of the scrotum. Cause of death was fatal
      hemorrhage. Since penis and the knife were missing at the scene and the blood
      stains were confined to the bed but not in the further apartment, further traces
      were disposed, the son of the deceased was suspicious of murder. The confession
      of the suspect in trial claimed a suicidal self-castration; this claimed self
      inflicted genital mutilation was in part in accordance with objective findings.

PMID- 8546565
TI  - [Electroshock devices as weapon].
AB  - 13 electric shock weapons were investigated. The authors measured the electrical
      output and observed the effects on corpses and test persons. The electric shock
      weapons produced only moderate pain and did not stop the disposing capacity. The
      electrocardiogram and the circulation parameters were not influenced. The
      electric shock weapons tested might have only a limited deterrent effect and
      might be able to cause fatal complications under circumstances. Drug use and
      heart disease might enhance the risk.

PMID- 8546566
TI  - [Dactyloscopy of mummified cadavers].
AB  - The identification of mummified bodies places high demands on the skills of a
      forensic fingerprinting specialist. From a variety of methods, he must be able to
      choose the most appropriate one to reproduce the skin ridges from fingers, which
      are often shrunk and deformed. This article introduces and discusses a method for
      indirect fingerprinting. In this method, a negative cast of the mummified
      fingertip is first produced with a silicon mass. This 3-dimensional negative is
      then filled with several layers of a white glue/talc mixture, until a skin-thick
      positive is attained. Using this artificial skin it is possible to reproduce, in
      a relatively short time, a fingerprint which is free of disturbing skin wrinkles
      and deformities.

PMID- 8546568
TI  - Pseudoaneurysm of the inferior epigastric artery. Pathogenesis, diagnosis, and
      treatment.
AB  - We present a new case of pseudoaneurysm of the abdominal wall, subsidiary to the
      inferior epigastric artery, associated with the use of discharge sutures.
      Pseudoaneurysms are a well-known complication of surgery, puncture, or trauma.
      Pseudoaneurysms of the inferior epigastric artery are very infrequent. We know of
      only two cases in the literature. In both cases, the pseudoaneurysm was
      associated with the use of discharge sutures. We discuss its pathogenesis,
      diagnosis, and treatment.

PMID- 8546567
TI  - [Video documentation in forensic practice].
AB  - The authors report in part 1 about their experiences with the Canon Ex1 Hi
      camcorder and the possibilities of documentation with the modern video technique.
      Application examples in legal medicine and criminalistics are described autopsy,
      scene, reconstruction of crimes etc. The online video documentation of
      microscopic sessions makes the discussion of findings easier. The use of video
      films for instruction produces a good resonance. The use of the video
      documentation can be extended by digitizing (Part 2). Two frame grabbers are
      presented, with which we obtained good results in digitizing of images captured
      from video. The best quality of images is achieved by online use of an image
      analysis chain. Corel 5.0 and PicEd Cora 4.0 allow complete image processings and
      analysis. The digital image processing influences the objectivity of the
      documentation. The applicabilities of image libraries are discussed.

PMID- 8546569
TI  - Simplified inflow control using stapling devices for major hepatic resection.
AB  - We describe the efficacy of a new technique for hepatic inflow division using
      stapling devices in major hepatic resections. We studied 28 consecutive patients
      who underwent major hepatic resection at a tertiary referral center by en masse
      inflow control of Glisson's pedicle in 1993 and 1994, of whom 10 underwent inflow
      control with stapling devices. Although stapling devices were used for larger
      tumors (mean +/- SD, 12.2 +/- 8.6 vs 5.7 +/- 5.0 cm; P = .02), the operation time
      (261 +/- 57 vs 301 +/- 143 minutes), operative blood loss (2071 +/- 1318 vs 4792
      +/- 6586 mL), postoperative intra-abdominal bleeding (0% [0/10] vs 17% [3/18]),
      and hospital stay (16.0 +/- 2.6 vs 20.6 +/- 7.4 days) were favorable for
      resections with staplers vs resections without staplers; the overall incidences
      of postoperative complications (40% [4/10] vs 39% [7/18]) and hospital death (10%
      [1/10] vs 6% [1/18]) were comparable in the two groups. We conclude that stapling
      devices allow simple, quick, and safe en masse inflow control in major hepatic
      resections.

PMID- 8546570
TI  - The recurrence rate in hernia surgery.

PMID- 8546571
TI  - The reemergence of mycobacterial infections.
AB  - In the early half of this century, infections due to Mycobacterium tuberculosis
      were quite common and were frequent causes of death and morbidity among the world
      population. Surgeons in the 1930s were quite sensitive to making the diagnosis of
      tuberculosis. All surgeons had considerable experience with thoracic surgical
      procedures for pulmonary tuberculosis. Moreover, tuberculosis was a significant
      cause of occupational infection among surgeons and other physicians. Thus, being
      able to diagnose the disease quickly and accurately was not only in the patient's
      best interest, but also allowed appropriate precautions to be exercised so that
      occupational infections of the health care team could be minimized.

PMID- 8546572
TI  - Hepatitis C. A clinical update.
AB  - Hepatitis C virus is now known to be the causative agent for at least 90% of non
      A, non-B hepatitis cases. In the few years since its characterization, much has
      been learned about this virus and the scope of its disease. It now appears that
      close to 100% of infections may become chronic, with delayed but potentially
      devastating consequences. The treatment options for hepatitis C remain limited
      and less than satisfactory. A vaccine seems to be a distant goal, but other
      strategies for treatment may be closer. For now, the best option remains
      prevention.

PMID- 8546573
TI  - Interleukin-6 delays neutrophil apoptosis.
AB  - BACKGROUND: Neutrophil (PMN) apoptosis promotes the phagocytosis of PMNs without
      inciting an inflammatory response or local cytotoxic effect. This is important in
      the normal resolution of inflammatory processes and the control of tissue injury.
      Conversely, a delay in PMN apoptosis may facilitate PMN-mediated organ
      dysfunction by extending PMN functional integrity at an inflammatory site.
      Elevated circulating and tissue levels of interleukin-6 (IL-6) have been
      associated with postinjury organ dysfunction, and IL-6 appears to augment PMN
      cytotoxic functions. Therefore, we hypothesized that IL-6 delays PMN apoptosis,
      thereby enhancing PMN-mediated cytotoxicity. METHODS: Neutrophils isolated from
      healthy human donors were incubated for 24 hours in enriched RPMI 1640 cell
      culture medium at 37 degrees C in 5% carbon dioxide. Subgroups were incubated
      with IL-6, heat-denatured IL-6, or buffer alone. Apoptosis was assessed
      morphologically using acridine orange-ethidium bromide stain, and biochemically
      by DNA gel electrophoresis. Functional capacity of PMNs was assessed by
      superoxide generation after activation with phorbol myristate acetate or platelet
      activating factor plus formyl-methionyl-leucyl-phenylalanine. RESULTS: Treatment
      with IL-6 resulted in a greater population of surviving (nonapopototic) PMNs
      after 24 hours. In addition, the IL-6-treated population produced more superoxide
      after 24 hours than did the untreated or heat-denature IL-6-treated groups, after
      either activating stimulus. CONCLUSIONS: Interleukin-6 delays PMN apoptosis,
      resulting in a larger population of surviving PMNs with a greater collective
      capacity for superoxide production. This could potentially facilitate PMN
      mediated tissue injury and may be a mechanism whereby IL-6 contributes to organ
      dysfunction.

PMID- 8546574
TI  - Expression of human neutrophil L-selectin during the systemic inflammatory
      response syndrome is partly mediated by tumor factor alpha.
AB  - BACKGROUND: Rolling of neutrophils on the vascular endothelium is a requisite
      step to transmigration to areas of infection or inflammation, and this is
      regulated in part by the neutrophil cell adhesion molecule L-selectin.
      OBJECTIVES: To compare L-selectin expression in patients with systemic
      inflammatory response syndrome (SIRS) and healthy age-matched control subjects
      and to determine whether tumor necrosis factor alpha modulates L-selectin
      expression on human neutrophils. SETTING: A tertiary care surgical intensive care
      unit at a university teaching hospital. SUBJECTS: Patients identified with SIRS
      (American College of Critical Care Physicians and Society of Critical Care
      Medicine criteria) were compared with healthy age-matched control subjects.
      Venous blood samples that were obtained from healthy laboratory control subjects
      were used to examine the time course of L-selectin expression. MAIN OUTCOME
      MEASURES: Neutrophil L-selectin expression was determined by flow cytometry in
      patients with SIRS and control subjects. Tumor necrosis factor alpha
      concentrations were determined in blood and exudative fluid from patients with
      SIRS. Neutrophil L-selectin expression was measured during a 45-minute time
      course in the presence of recombinant human tumor necrosis factor alpha and N
      formyl-methionyl-leucyl-phenylalanine. RESULTS: Circulating neutrophils from
      patients with SIRS had significantly less L-selectin expression than did control
      subjects. Tumor necrosis factor alpha at concentrations similar to those found in
      exudative fluid caused a dose- and time-dependent decrease in neutrophil L
      selectin expression. CONCLUSION: Tumor necrosis factor alpha may act as a
      paracrine modulator of site-specific neutrophil rolling, adhesion, and exudation
      via mechanisms that involve the down-regulation of L-selectin.

PMID- 8546575
TI  - Development of multiple organ dysfunction syndrome in critically ill patients
      with perforated viscus. Predictive value of APACHE severity scoring.
AB  - OBJECTIVE: To determine whether scoring on the Acute Physiology and Chronic
      Health Evaluation (APACHE) III at admission can predict the development of
      multiple organ dysfunction syndrome and mortality in critically ill surgical
      patients. DESIGN: Prospective, inception-cohort study. SETTING: Surgical
      intensive care unit of an urban, tertiary-care hospital. PATIENTS: One hundred
      fourteen critically ill patients with surgically treated perforated
      gastrointestinal viscus. INTERVENTIONS: Calculation of APACHE II and APACHE III
      scores 24 hours after admission to the surgical intensive care unit and serial
      quantitation of organ dysfunction for the duration of critical care according to
      two different predefined scoring systems. Patients were stratified by survival,
      the development of organ dysfunction, and colon vs noncolonic perforation. MAIN
      OUTCOME MEASURES: Hospital mortality, length of stay in the surgical intensive
      care unit, and the development of organ dysfunction or overt organ failure.
      RESULTS: The mean (+/- SEM) APACHE II and APACHE III scores were 17.4 +/- 0.6
      (range, 6 to 37) and 59.0 +/- 2.2 (range, 15 to 141), respectively. The incidence
      of organ dysfunction was 73% (64% in survivors). All severity scores were
      identical for colon perforation and noncolonic perforation subgroups.
      Nonsurvivors invariably had organ dysfunction. Overall length of stay in the
      intensive care unit was 12.0 +/- 1.6 days (8.7 +/- 1.2 days for survivors and
      22.7 +/- 5.0 days for nonsurvivors). The APACHE scores and organ dysfunction or
      failure scores were significantly higher in nonsurvivors, and APACHE scores were
      higher in survivors with organ dysfunction than in those without it. Significant
      linear relationships were identified for APACHE II vs APACHE III scores (R2 =
      .66) and for all four combinations of APACHE scores and organ dysfunction or
      failure scores (R2 = .43 to .52). By multivariate analysis of variance,
      independent predictors of organ dysfunction or failure were APACHE III, increased
      age, and a prolonged stay in the surgical intensive care unit, but not the type
      of perforation. Neither APACHE II or APACHE III predicted mortality
      independently. CONCLUSIONS: The development of multiple organ dysfunction
      syndrome correlated with higher APACHE III scores but was independent of the type
      of perforation. Only the development of overt multiple organ failure predicted
      death. Combined use of APACHE III and the multiple organ dysfunction score
      provides improved prediction of multiple organ dysfunction syndrome, but further
      enhancements are needed before prediction of outcome in individual patients is
      reliable.

PMID- 8546576
TI  - Calcium and calmodulin regulate lipopolysaccharide-induced alveolar macrophage
      production of tumor necrosis factor and procoagulant activity.
AB  - BACKGROUND: Alterations in macrophage (M phi) function are responsible, in part,
      for adult respiratory distress syndrome and multiple organ failure developing in
      patients with sepsis. Elucidation and control of these M phi mechanisms during
      sepsis are crucial to our understanding of this disease and, ultimately, to
      improving survival of these patients. OBJECTIVE: To investigate the involvement
      of calcium flux in endotoxin-induced alveolar M phi production of tumor necrosis
      factor (TNF) and procoagulant (PC) activity. DESIGN: Rabbit alveolar M phi
      obtained by bronchoalveolar lavage were exposed to endotoxin in the form of
      lipopolysaccharide (LPS) extracted from Escherichia coli 0111:B4 in the presence
      of different specific calcium agonists and antagonists. The TNF expression was
      measured in the supernatant by L929 bioassays. The PC activity was determined in
      cell lysates by a one-step coagulation assay. RESULTS: Macrophages activated by
      LPS produce enormous levels of TNF and PC. Either W7 (20 mumol/L), a calmodulin
      antagonist, or TMB-8 (50 mumol/L), which prevents calcium release from the
      endoplasmic reticulum, inhibited production of both TNF and PC activity.
      Verapamil (50 mumol/L) alone or combined with TMB-8 significantly inhibited both
      TNF and PC production by LPS-stimulated M phi. Elevating intracellular calcium
      ([Ca2+]i), using the calcium ionophore, A23187, or thapsigargin alone, did not
      induce M phi production of TNF but significantly augmented LPS-stimulated TNF
      production. CONCLUSION: Our results indicate that increased intracellular calcium
      causing signal transduction activation through the calmodulin pathway is a
      necessary, but insufficient, component of the LPS signaling in M phi.

PMID- 8546577
TI  - Interleukin-10 attenuates the release of proinflammatory cytokines but depresses
      splenocyte functions in murine endotoxemia.
AB  - OBJECTIVE: To determine whether interleukin (IL)-10, besides its potent anti
      inflammatory properties, causes depression of splenocyte functions in a murine
      model of gram-negative endotoxemia. DESIGN: Mice (strain C3H/HeN) were injected
      intravenously with 1 mg of Escherichia coli lipopolysaccharide at 15 minutes
      after intravenous injection of either 200 U of recombinant murine IL-10 or saline
      solution. Serum levels of tumor necrosis factor alpha, IL-6, and IL-1 alpha were
      determined at 90 minutes and 12 hours after lipopolysaccharide challenge. In
      addition, splenocyte proliferation and lymphokine release (IL-2, IL-6, and
      interferon gamma) were measured. RESULTS: Pretreatment with IL-10 markedly
      reduced (P < .05) serum levels of tumor necrosis factor alpha (-79%), IL-6 (
      94%), and IL-1 alpha (-69%), but it significantly inhibited splenocyte
      proliferation (-32%) and IL-2 (-40%), IL-6 (-49%), and interferon gamma (-54%)
      release of splenocytes. CONCLUSIONS: Interleukin-10 prevents E coli
      lipopolysaccharide-induced cytokinemia but dampens antigen-driven cellular immune
      responses. Although IL-10 protects against the detrimental effects of
      proinflammatory cytokines by deactivation of macrophages, its immunosuppressive
      effect may augment susceptibility to repeated or continuous invasion of
      microorganisms, as it is observed during clinical sepsis.

PMID- 8546578
TI  - Effects of hyperoxia on bacterial translocation and mortality during gut-derived
      sepsis.
AB  - BACKGROUND: While hyperoxia is commonly used for treating carbon monoxide
      poisoning, chronic nonhealing ulcers, acute traumatic and chronically ischemic
      wounds, and refractory osteomyelitis, its efficacy is unproven in numerous
      clinical situations, including treatment during severe sepsis. OBJECTIVE: To test
      the effects of hyperoxia on bacterial translocation and mortality during gut
      derived sepsis in a clinically relevant model of infection. METHODS: Balb/c mice
      were gavaged with 10(9) Escherichia coli and subjected to a 20% burn injury.
      Then, the animals were randomized to receive hyperoxia for different periods of
      time. Survival and the extent of translocation were determined, as well as
      intestinal histologic features. RESULTS: Hyperoxia treatment preserved gut
      morphology and improved gut barrier function, decreasing the amount of bacterial
      translocation. Short-term (4- or 8-hour) hyperoxia (100% oxygen) treatment
      improved survival only on day 1 after injury but did not affect the final
      outcome. Short-term (8-hour) hyperoxia (100% oxygen) plus 5-day 40% oxygen
      environment significantly improved long-term survival. CONCLUSION: Tissue pO2 may
      be an important regulator of gut barrier function. Hyperoxia treatment appears to
      play a major role in preserving gut barrier function.

PMID- 8546579
TI  - Surgery in South Africa.
AB  - The practice of surgery in South Africa ranges from full-time service in state
      funded and academic hospitals serving a largely indigent population to a private
      sector for medically insured patients. Surgical training occurs at eight medical
      schools, and specialist registration is obtained after 4 to 5 years with either a
      university-conferred degree or a fellowship from the College of Surgeons of South
      Africa. The wide spectrum of First- to Third-World diseases and the high
      incidence of trauma provide comprehensive experience for practical training.
      Surgical standards are uniformly high, matching and sometimes pioneering the very
      best of Western medicine. The health care system is undergoing radical change to
      correct the imbalances of the apartheid era. Academic institutions are under
      pressure, and with incipient major financial cutbacks, there is concern that the
      proud record of service, teaching, and research excellence may be compromised. To
      facilitate the mission of broadening health care services, diploma training in
      surgery for rural practitioners is being developed. Outreach programs and closer
      liaisons with surgical societies in sub-Saharan African countries have also been
      initiated.

PMID- 8546580
TI  - The mode of Roux-en-Y reconstruction affects motility in the efferent limb.
AB  - OBJECTIVES: To compare motility of a Roux-en-Y esophagojejunostomy after total
      gastrectomy with normal jejunal motility and to determine the effect on motility
      of the incorporation of a pouch in the reconstruction. DESIGN: Jejunal motility
      in normal subjects was compared with jejunal motility in the Roux-en-Y
      reconstruction with and without a Hunt-Lawrence pouch. SETTING: The case were
      collected during a 4-year period at a university hospital. The mean time from
      resection to study was 14 months (range, 4 to 49 months). PATIENTS: Seven control
      patients were compared with 10 patients with a Roux-en-Y reconstruction and 17
      with a Roux-en-Y and Hunt-Lawrence pouch. OUTCOME MEASURE: The fasting-state
      motility of the jejunum used for reconstruction was measured by a water-perfused
      manometric system for 2 to 4 hours with the subject in the supine position.
      RESULTS: Compared with normal subjects, patients with a Roux-en-Y
      esophagojejunostomy without a pouch had an increased number of phases of the
      interdigestive motor complex per hour (P < .05). The phases were of shorter
      duration with a random sequence and increased total time spent in the quiescent
      phase 1 (P < .05). In patients with a pouch, no differences were detected between
      the motility in the pouch and the efferent limb. Compared with those without a
      pouch, there were significantly fewer orthograde interdigestive motor complex
      phase 3 fronts and more total time spent in phase 1 (P < .05). CONCLUSIONS:
      Construction of a gastric substitute from jejunum leads to substantial motility
      changes. The addition of a pouch decreases the overall activity, which may
      contribute to the storage function of the pouch.

PMID- 8546581
TI  - Expression of p53 protein in colorectal carcinoids.
AB  - OBJECTIVE: To determine the frequency and prognostic significance of p53 protein
      expression in colorectal carcinoid tumors. DESIGN: Thirty-one paraffin-embedded
      specimens of colorectal carcinoid tumor were studied by immunohistochemical
      staining to detect p53 protein expression. The association of p53 expression with
      tumor site, tumor size, invasion level, tumor stage, DNA pattern, and patient
      survival were analyzed. RESULTS: p53 protein was detected in five (16%) of 31
      colorectal carcinoid tumors. There was a correlation between p53 overexpression
      and tumor site, tumor size, tumor stage, and DNA ploidy (P < .05) but not for the
      depth of tumor invasion (P = .06). In addition to tumor size, invasion, stage,
      and DNA aneuploidy, p53 protein overexpression was also indicative of a poor
      prognosis (P < .001). CONCLUSIONS: The overexpression of p53 protein is uncommon
      in colorectal carcinoid tumors. However, the expression of p53 protein has a
      correlation with clinicopathologic-predicting criteria in colorectal carcinoid
      tumors and may be used as an associated prognostic parameter to assess patient
      survival.

PMID- 8546582
TI  - Results of 280 liver resections for hepatocellular carcinoma.
AB  - OBJECTIVE: To evaluate the recent results of liver resection in patients with
      hepatocellular carcinoma. DESIGN: Retrospective study. SETTING: A university
      hospital in Japan. PATIENTS: Two hundred eighty patients who underwent liver
      resection with complete extirpation of hepatocellular carcinoma from 1985 to
      1993. MAIN OUTCOME MEASURES: Morbidity and survival after operation and the
      pathologic features of hepatocellular carcinoma according to the TNM
      classification of the International Union Against Cancer. RESULTS: More than 40%
      of the patients with stages I and II disease underwent a partial resection of the
      liver, whereas 50% of those with stages III and IVA were operated on with more
      than a bisegmentectomy. Fifty percent of all patients had no postoperative
      complications. The morbidities included intra-abdominal abscess (7%), bile
      leakage (5%), and hepatic failure (4%, of whom half died; mortality rate, 2%).
      Histopathologically, 32% of the stage I tumors were well differentiated (grade
      1), while, in stage III, 56% had portal invasion and 61% had daughter lesions in
      the liver. The cumulative survival rates of patients with stages I, II, and III
      disease and all patients at 5 years were 69%, 52%, 32%, and 50%, respectively,
      while the disease-free survival rates at 5 years were 38%, 34%, 17%, and 29%,
      respectively. CONCLUSION: The recent results of liver resection for
      hepatocellular carcinoma are generally satisfactory; however, the recurrence rate
      is still high.

PMID- 8546583
TI  - Bacterial translocation in a large-animal model of small-bowel transplantation.
      Portal vs systemic venous drainage and the effect of tacrolimus
      immunosuppression.
AB  - OBJECTIVE: To study whether bacterial translocation is more prevalent after small
      bowel transplantation with systemic venous drainage (SVD) vs portal venous
      drainage (PVD) and whether it is influenced by immunosuppression. DESIGN: We
      performed 15 small-bowel transplantations in pigs. Group 1 (n = 5) had SVD and no
      immunosuppression; group 2 (n = 6), PVD and no immunosuppression; and group 3 (n
      = 4), PVD and immunosuppression with tacrolimus and methylprednisolone sodium
      succinate. Portal and systemic blood, portal and mesenteric lymph nodes, and
      liver were cultured in donors and recipients on postoperative day 0 (POD 0) and
      in recipients on postoperative day 3 (POD 3). Jejunal and ileal contents were
      also sampled at these times. SUBJECTS: Outbred male Yorkshire-Landrace pigs. MAIN
      OUTCOME MEASURES: (1) Blood and tissue bacterial cultures, (2) blood endotoxin
      levels, and (3) histopathologic examination. RESULTS: Cultures were positive for
      bacteria in 32% (16/50) of samples on POD 0 and 88% (22/25) on POD 3 in group 1,
      in 18% (11/60) of samples on POD 0 and 97% (29/30) on POD 3 in group 2, and in 8%
      (3/40) of samples on POD 0 and 95% (19/20) on POD 3 in group 3. Systemic blood
      cultures were positive for bacteria on POD 3 in 60% (3/5) of pigs in group 1, 83%
      (5/6) in group 2, and 100% (4/4) in group 3. Significantly more bacteria were
      present in the ileum than in the jejunum on POD 0 in group 2; this difference
      approached significance in groups 1 and 3. Bacterial numbers were identical in
      the ileum and jejunum by POD 3 in all groups. Circulating endotoxin levels were
      significantly elevated on POD 3 vs POD 0 only in group 1. Endotoxin levels were
      not significantly different between the SVD group (group 1) and either PVD group
      (groups 2 and 3). CONCLUSIONS: Bacterial translocation is prevalent after small
      bowel transplantation in pigs whether PVD or SVD is used. Immunosuppression with
      tacrolimus does not prevent bacterial translocation but may reduce systemic
      endotoxemia.

PMID- 8546584
TI  - Features of autoimmunity in the abdominal aortic aneurysm.
AB  - PURPOSE: Previous work has revealed that nonspecific abdominal aortic aneurysms
      (AAAs) have a prominent infiltration of inflammatory cells and that soluble
      extracts of AAA tissue are rich in immunoglobulins. These observations raise the
      question whether autoimmune mechanisms play a role in the pathogenesis or
      progression of AAA disease. The hypothesis of this investigation was that IgG
      purified from aneurysmal specimens would be immunoreactive with normal components
      of the aortic wall (by means of immunohistochemistry) and with soluble proteins
      extracted from normal aortic tissue (by Western immunoblotting methods). METHODS:
      Immunoglobulin G extracted from AAA homogenates was used to detect
      immunohistochemical reactivity to connective tissue components in fixed sections
      of normal aorta obtained from an organ donor. Immunoblotting techniques were used
      to compare the reactivity of IgG (detected with secondary goat antihuman
      antibody) from 14 patients with AAA with soluble proteins extracted from normal
      and aneurysmal aortas. Immunoglobulins G purified from extracts obtained from
      nine patients with no AAA were used for control experiments. RESULTS: A unique
      band at approximately 80 kd was visualized when the filters were probed with IgG
      from 11 (79%) of 14 patients with AAA compared with only one (11%) of nine
      control subjects (P = .002 by Fisher's exact test). Immunoglobulins G from
      patients with AAA codistributed with matrix fibers in normal aortic sections,
      particularly in the adventitia (suggestive of a microfibrillar component).
      CONCLUSION: Our findings suggest that there are autoimmune features of AAA
      disease that might not only be informative in terms of AAA origin but also lead
      to more precise forms of pharmacologic down-regulation of disease progression.

PMID- 8546585
TI  - Selection criteria for preoperative endoscopic retrograde
      cholangiopancreatography in the laparoscopic era.
AB  - BACKGROUND: Indicators for cholangiography were originally designed to select
      patients at risk for common bile duct (CBD) stones for intraoperative
      cholangiography. OBJECTIVE: To refine these criteria to apply to the much more
      invasive procedure of preoperative endoscopic retrograde cholangiopancreatography
      (ERCP). DESIGN: Retrospective review of selection criteria for ERCP in
      consecutive patients referred over 18 months following the introduction of
      laparoscopic cholecystectomy. SETTING: Two ERCP units in adjacent teaching
      hospitals. PATIENTS: Three hundred seventeen patients with gallstones and in situ
      gallbladders. INTERVENTION: Common bile duct imaging at ERCP. MAIN OUTCOME
      MEASURES: Abnormalities justifying ERCP. RESULTS: Abnormalities justifying ERCP
      were found in 66% of patients. This group differed significantly from those with
      normal ducts, with more being referred with abnormal results of all liver
      function tests (P < .001), jaundice (P < = .001), a dilated CBD on ultrasound (P
      < .001), or CBD stones on ultrasound (P < .001). On the other hand, patients with
      normal ducts were significantly more likely to have been referred with
      pancreatitis (P = .003) or elevated results of individual liver function tests (P
      < .001). A logistic regression model using age, presence of jaundice at ERCP,
      levels of alkaline phosphatase and albumin, and ultrasonography showing dilated
      ducts or visible CBD stones was found to have a specificity of 75% and a
      sensitivity of 89%. Past pancreatitis or elevated results of individual liver
      function tests were not predictive factors. CONCLUSION: The use of such a model
      rather than individual criteria would improve the selection of patients for
      preoperative ERCP, optimizing its role in the laparoscopic era.

PMID- 8546586
TI  - Aerobic and anaerobic microbiology of superficial suppurative thrombophlebitis.
AB  - OBJECTIVE: To study the aerobic and anaerobic microbiologic characteristics of
      superficial suppurative thrombophlebitis. DESIGN: Retrospective review of
      microbiologic and clinical data. SETTING: Navy Hospital in Bethesda, Md. RESULTS:
      Sixty-one isolates, 36 aerobic and 25 anaerobic, were isolated from samples
      obtained from 42 patients. Aerobic bacteria only were found in 26 (62%) patients;
      anaerobic only, in 11 (26%); and mixed aerobic and anaerobic bacteria, in five
      (12%). The predominant aerobic bacteria were Staphylococcus aureus (n = 9),
      Escherichia coli (n = 7), Pseudomonas aeruginosa (n = 4), and Klebsiella sp (n =
      3). The most frequently recovered anaerobic bacteria were Peptostreptococcus sp
      (n = 8), Propionibacterium acnes (n = 6), Bacteroides fragilis group (n = 5),
      Prevotella intermedia (n = 3), and Fusobacterium nucleatum (n = 3).
      Propionibacterium acnes and Peptostreptococcus sp were associated with cannula
      related superficial suppurative thrombophlebitis; B fragilis and
      Enterobacteriaceae, with abdominal surgery or pathology; and S aureus and P
      aeruginosa and Citrobacter sp, with burns. CONCLUSION: These data illustrate the
      importance of anaerobic bacteria in superficial suppurative thrombophlebitis.

PMID- 8546587
TI  - Factors affecting conversion of laparoscopic cholecystectomy to open surgery.
AB  - OBJECTIVE: To identify the risk factors predictive of conversion of laparoscopic
      cholecystectomy to open surgery. DESIGN: Demographic, ultrasonographic, and
      operative data of patients who underwent laparoscopic cholecystectomy were
      analyzed. Factors affecting conversion to open surgery were identified with
      statistical analysis. SETTING: A tertiary referral center. PATIENTS: Five hundred
      patients who underwent laparoscopic cholecystectomies at our institution between
      March 1991 and July 1994. The patients' data had been prospectively collected.
      INTERVENTION: Standard laparoscopic techniques with selective preoperative
      endoscopic retrograde cholangiopancreatography. MAIN OUTCOME MEASURE: Conversion
      of laparoscopic cholecystectomy to open surgery for management of technical
      difficulties or intraoperative complications. RESULTS: Increased risk of
      conversion with statistical significance was found in patients older than 65
      years, obese patients, patients who underwent interval elective laparoscopic
      cholecystectomy for acute cholecystitis, patients with ultrasonographic findings
      of thickened gallbladder wall, patients seen during the early learning phase of
      the series, and patients whose surgery was performed by senior surgeons.
      Increased risk of conversion was not found with patients' sex, previous lower
      abdominal surgery, history of acute pancreatitis or cholangitis, impaired liver
      function on presentation, or emergency laparoscopic cholecystectomy for acute
      cholecystitis. CONCLUSIONS: Risk factors, including patient factors,
      presentation, preoperative ultrasonography, and surgical experience, all
      contributed to the possibility of conversion. Knowledge of these factors may help
      in arranging the operating schedule, psychological preparation for the procedure,
      and planning of the duration of convalescence.

PMID- 8546588
TI  - [Acute effects of isosorbide mononitrate on blood circulation and myocardial
      ischemia in patients with coronary atherosclerosis].
AB  - PURPOSE: To evaluate the acute effects of isosorbide mononitrate on circulation,
      cardiac function and left ventricular segmental motility in patients with
      isquemic heart disease due to coronary artery disease. METHODS: Twenty-four
      patients with ischemic heart disease, 10 women, with mean age of 58 years, were
      studied during cardiac catheterization, at baseline condition and 5min after
      intravenous infusion of 0.3mg/kg of isosorbide mononitrate. RESULTS: After
      infusion of isosorbide mononitrate there were significant reduction in mean right
      atrial pressure no mean pulmonary artery pressure (< 0.0001), left ventricular
      and diastolic pressure (p < 0.004), left ventricular systolic pressure (p <
      0.002), maximum (p < 0.002) and mean (p < 0.008) aortic pressure, and left
      ventricular systolic volume (p < 0.004), as well as significant increase in the
      left ventricular ejection fraction (p < 0.001) and mean velocity of
      circunferential fibers shortening (p < 0.001). There was no significant
      modification of minimum aortic pressure, heart rate, cardiac output nor of left
      ventricular and diastolic volume. With respect of segmental motility of the left
      ventricle after medication, 38 kypokinetic segments normalized their motility, 4
      akinetic segments remained intact, and of the 21 dyskinetic segments, 6
      normalized, 8 became hypokinetic and 7 remained dyskinetic. CONCLUSION:
      Isosorbide mononitrate, when used as intravenous infusion, have a rapid and
      direct effect on systemic and pulmonary circulation, and improving segmental
      motility and left ventricular performance in patients with impaired left
      ventricular motility caused by ischemic heart disease.

PMID- 8546589
TI  - [Evaluation of the vagal efferent pathway in rats in the acute and chronic phases
      of myocardial infarction].
AB  - PURPOSE: To investigate the sensitivity of the muscarinic receptors to
      acetylcholine (Ach) and to vagal stimulation in rats during the acute and the
      chronic phases of myocardial infarction (MI). METHODS: Male albino rats were
      submitted to ligature of the descending anterior branches of the left coronary
      artery to produce MI. Control rats (Con) were submitted to a sham surgery. The
      animals were studied 1-3 days (acute phase) or 30 days (chronic phase) after
      surgery. Under anesthesia (ketamine+xylazine) the right vagus nerve was isolated
      at the neck and stimulated with suprathreshold pulses (2ms, 1-64Hz). Atrial and
      ventricular rates were measured in the ECG recording. Dose-response curve to Ach
      (5-80 micrograms) was studied in the isolated hearts perfused according to the
      Langendorftechnique. Atrial and ventricular rates were evaluated through the
      surface electrogram recording. The left ventricular pressure was measured with an
      intraventricular balloon. RESULTS: Basal heart rate in the anesthetized animals
      was similar in Con and MI rats. The vagal stimulation produced a frequency
      dependent reduction of the heart rate. This reduction was less intense in the MI
      groups to stimulation rates of 32 and 64Hz. It was not observed any difference in
      the sensitivity of sinus and AV nodes to exogenous Ach in infarcted hearts. The
      reduction of the systolic pressure obtained after Ach administration to the
      hearts paced artificially (3.3Hz) was similar in MI and Con hearts. CONCLUSION:
      MI hearts were less sensitive to vagal stimulation than Con hearts. Since the in
      vitro effects of Ach remained unchanged after infarction, these results suggest
      an impairment of the cardiac neuroeffector vagal synapse. This may contribute to
      a less efficient control of the heart rate by the parasympathetic pathway in
      infarcted individuals.

PMID- 8546590
TI  - [Analysis of the junctional rhythm characteristics in patients with nodal reentry
      tachycardia treated with slow pathway radiofrequency ablation].
AB  - PURPOSE: To study the quantitative and qualitative aspects of junctional rhythm
      (JR) during radiofrequency (RF) catheter ablation of slow pathway in
      atrioventricular nodal reentrant tachycardia. METHODS: Twenty five patients, 5
      males, ages ranging from 15 to 76 years, with recurrent atrioventricular nodal
      reentrant tachycardia, underwent to RF catheter ablation of slow pathway. During
      RF applications (40V, duration 60s) electrocardiographic was continuously
      recorded. The recordings were posteriorly used to study the presence and
      characteristics of JR (number of episodes, frequency and time of onset) at the
      effective and ineffective RF sessions. All variables were expressed as median and
      mean +/- SD. Univariate analysis of the effects of each variable on success or
      failure of ablation were performed using x2 test. A p value < 0.05 was considered
      significant. RESULTS: One hundred forty nine RF sessions were performed, 25
      effective and 124 ineffective (mean per patient 6, range 1 to 22). JR was present
      in 18 of 25 effective and 44 of 124 ineffective sessions (p < 0.05). Mean time of
      appearance was 12s, occurring later this time in 9 of 18 effective and in 10 of
      44 ineffective sessions (p < 0.05). Mean number of episodes was 3, occurring
      higher number in 7 of 18 effective and in 4 of 44 ineffective sessions (p <
      0.05). Median of frequency of JR was 100bpm; 11 of 18 effective and 15 of 44
      ineffective sessions presented higher frequencies (p < 0.05). CONCLUSION: JR
      during slow pathway ablation is a sensitive marker of ablation success. JR
      predictor of success has higher number of episodes, higher frequency and later
      time of appearance than that one of ineffective sessions.

PMID- 8546592
TI  - [Chronic Chagas cardiopathy as a model for an insight on the pathogenesis of
      arrhythmogenic right ventricular cardiomyopathy].

PMID- 8546591
TI  - [Relationship of average level and variability of blood pressure with the
      geometry of the left ventricle in systemic hypertension].
AB  - PURPOSE: To study the relation between the average level and variability of blood
      pressure (VBP) obtained by ambulatory monitoring (AMBP) and the geometric pattern
      (GP) of the left ventricle (LV) obtained by echocardiography (ECHO) in patients
      with hypertension (Hy) METHODS: AMBP and ECHO were performed in 37 patients with
      Hy, divided into three groups: group A--11 women using antihypertensive therapy
      (AH); group B--15 men using AH and group C--7 male and 4 female without AH. The
      GP of LV was obtained by ECHO based on mass index (MI) and relative thickness of
      the wall (RTW). Mean systolic (MSBP) and diastolic (MDBP) were analyzed during
      daytime (DT) and nighttime (NT) periods. VBP was defined by mean standard
      deviation (SD) of mean pressures considered. RESULTS: In G-A, there was a
      significant association between the MI and both VBP and MSBP (r = 0.65 and p <
      0.005, r = 0.61, and p < 0.005, respectively), and MSBP and VBP during the DP (r
      = 0.64 and p < 0.005, r = 0.75, and p < 0.005). In G-B, there was a relation
      between the LVRTW (r = 0.55 and p < 0.005), and MSBP during the DP (r = 0.65 and
      p < 0.005). In G-C, there was a significant association (p < 0.005) between the
      MI and the MDBP in the DP and with the MSBP in the NP (r valueS ranged from 0.51
      to 0.66). There was also a significant relation (p < 0.005) between the LVRTW and
      the SD of all variables in both DP and NP (r ranged from 0.47 to 0.78 and mean
      diastolic in the wakeful period (r = 0.42 to 0.78) and MDBP in the DP (r = 0.42
      and p < 0.05). CONCLUSION: Both the increase in VBP and the mean BP are involved
      in the changes of LVGP in Hy.

PMID- 8546593
TI  - [Surgical treatment of congenital fistulas of the coronary artery].
AB  - PURPOSE: To evaluate the surgical result of the cases of congenital fistulae of
      the coronary artery. METHODS: Seven patients were surgically treated since
      January 80 until February 94. The ages ranged from 3 days to 52 years old. The
      diagnosis was suspected by echocardiogram and established by cardiac
      catheterization. RESULTS: Regarding the clinical status, 3 (42.85%) patients were
      asymptomatic, 3 (42.85%) presented congestive heart failure and 1 (14.28%)
      precordial pain and palpitation. The fistulae, located in inferior wall of the
      right ventricle in 1 (14.28%) patient, apex of the right ventricle in 1 (14.28%),
      right atrium in 3 (42.85%), and coronary sinus in 1 (14.28%), were isolated in 4
      (57.17%), 1 (14.28%) also had fixed subaortic stenosis, 1 (14.28%) had previously
      undergone the ligate of the ductus arteriosus and 1 (14.28%) also had aortic
      coarctation and ductus arteriosus. After surgical treatment, 5 (85.72%) had
      follow up abnormalities, showing good clinical outcome; 1 (14.28%), that also had
      aortic and subaortic stenosis, followed with minimal aortic regurgitation and
      poor left ventricular performance; 1 (14.28%), that had aortic coarctation and
      ductus arteriosus, who had been operated on in unfavourable hemodynamic
      conditions, died 5 days after surgery. CONCLUSION: Surgical correction should be
      proposed as a treatment of the congenital fistulae of the coronary artery, since
      it is technically feasible, and has low in-hospital mortality and morbidity.

PMID- 8546594
TI  - [Surgical treatment of infective endocarditis].
AB  - PURPOSE: To analyse, retrospectively, 83 patients with infective endocarditis
      (IE) that were operated during the acute phase of the disease and to identify
      possible subgroups with distinct mortality. METHODS: Between 1985 to 1990, 83
      patients comprised the subject of this analysis. Fifty-one (61%) were male, aged
      between 3 months to 71 years, mean of 31.4 +/- 16.7 years. RESULTS: We could
      identify two subgroups that were most frequently operated on: the left side IE
      and the Staphylococcus aureus; and 77 (43%) had left sided IE (p < 0.001). When
      discriminated accordingly to the specifically etiologic agent (Staphylococcus
      aureus) this difference continues to be statistically significant: of 29 left
      sided IE by this agent 13 (45%) were operated on, whereas from 22 right sided IE
      by the same agents, just 3 (14%) were operated on (p < 0.05). The two major
      etiologic agents did not show any statistically significant difference in the
      number of patients that needed to be operated on: on those 51 patients with
      Staphylococcus aureus IE, 16 (31%) were treated surgically, while from the 60
      patients with Streptococcus viridans, 22 (37%) underwent to surgical procedure (p
      NS). The mortality in the patients treated by surgery was 32%, and those with
      Staphylococcus aureus IE were responsible for 46% of the total surgical deaths.
      CONCLUSION: Surgical treatment were most frequently used in the patient with left
      sided IE independently of the etiologic agent.

PMID- 8546595
TI  - [Demographic profile and work situation of patients with Chagas disease].
AB  - PURPOSE: To evaluate the social profile and work habits in patients with Chagas'
      disease. METHODS: We studied 284 ambulatory patients age ranged 21 to 74 years,
      female (62.3%) and married people (71.8%) divided according to their activities
      in three groups: active workers--121 (42.7%); under social security--93 (32.8%);
      housewives--61 (21.4%); unemployed people--9 (3.1%). RESULTS: The majority of
      them were in stage II of Chagas' disease, 123 (43.3%) for both sexes. Migratory
      characteristics in this population was observed, with the search for work as the
      main reason for this. The level of education was low, considerably affecting the
      kind of profession. CONCLUSION: Patients with Chagas' disease are originally from
      the rural area and migrate to urban area in order to improve economic conditions.
      They show unfavourable social conditions, with inadequate level of education and
      lack of professional gratifications.

PMID- 8546596
TI  - [Pulmonary vein stenosis. Report of 2 cases and review of the literature].
AB  - Topical congenital pulmonary vein stenosis is a uncommon defect, both isolated or
      associated to other cardiac abnormalities. Only the localization of the lesions
      seems to affect the survival, because 60% of survival cases has unilateral
      stenosis; the severity of associated cardiac lesions become the prognosis poor.
      We describe two cases: 1st case, a 43 days old boy presented with heart failure
      and convulsion and had a diagnosis of pulmonary hypertension, atrial septal
      defect and tricuspid regurgitation, without pulmonary abnormalities. He had
      recurrent pulmonary infections and a cerebral ischemia in the following months,
      and died at 15 months of age for sepsis. Autopsy revealed stenosis and atresia in
      all pulmonary veins, with venous and arterial hypertension. There was also aortic
      hypoplasia and aortic and tricuspid valves indifferentiation; 2nd case, a 7 days
      old girl had a diagnosis of aortic coarctation and atrial and ventricular septal
      defects. Surgical corrections, at 38 and 46 days old, firstly of the aortic
      coarctation and after for the septal defects, disclosed and relief a supra-valvar
      mitral stenosis, but she remained on heavy respiratory insufficiency. At 6 months
      old, she returned to the hospital with dyspnea and cianosis, heart failure and
      hemoptisis; a sepsis developed and she died. At autopsy, there were severe
      pulmonary vein stenosis on the left and in the superior right veins, with
      pulmonary hypertension and hemorrhage.

PMID- 8546597
TI  - [Case 4/95 (Faculdade de Medicina do Triangulo Mineiro)].

PMID- 8546598
TI  - [The effect of urapidil on blood pressure, renal hemodynamics, lipid and glucose
      metabolism].
AB  - PURPOSE: To evaluate the effects of urapidil on blood pressure (BP), renal
      hemodynamics and lipid and glucose metabolism, in patients with mild-to-moderate
      uncomplicated essential hypertension. METHODS: Fifteen hypertensive patients,
      aged 38-64 year-old were studied by ambulatory blood pressure monitoring system
      (ABPM). It was also evaluated: 1) the creatinine clearance; 2) the effective
      renal plasma flow by use of a single plasma sample after injection of
      orthoiodohippurate; 3) the serum triglycerides, cholesterol, and HDL-cholesterol;
      4) blood levels of glucose and insulin. The urapidil dose ranged from 60 to 180
      mg/day, according to the individual response. RESULTS: The values after four
      weeks washout-placebo and active treatment with urapidil showed: the
      systolic/diastolic BP was reduced from 157.7 +/- 6/108.0 +/- 2 on placebo to
      140.4 +/- 4/97.3 +/- 3 mmHg (p < 0.05/p < 0.01) after urapidil, respectively,
      whereas heart rate was unchanged. The percentage of elevated systolic and
      diastolic BP values during 24h (BP load) was reduced from 60.9% to 54.4% and from
      60.8% to 50.3%, respectively. Effective renal plasma flow, glomerular filtration
      rate, filtration fraction and renal vascular resistance were unaltered by
      treatment. Significant increase in HDL-cholesterol was observed (from 39.5 +/-
      3.6 on placebo vs 49.2 +/- 4.8 mg/dl (p < 0.01) after urapidil. Total
      cholesterol, LDL-cholesterol and triglycerides levels were not modified with
      treatment. Circulating plasma glucose and insulin remained unchanged. CONCLUSION:
      Urapidil is an effective antihypertensive agent without deleterious effect on
      renal hemodynamics, lipid and glucose metabolism.

PMID- 8546599
TI  - [Laennec and the stethoscope. Symbols of modern medicine].

PMID- 8546600
TI  - [Angioplasty, surgical, or clinical treatment. Therapeutic options for
      obstructive coronary artery disease].

PMID- 8546601
TI  - [Active compression-decompression in cardiopulmonary resuscitation].

PMID- 8546602
TI  - [Acute effect of isosorbide mononitrate on blood circulation and myocardial
      ischemia in patients with atherosclerosis].

PMID- 8546603
TI  - [Substitutive treatment of renal function].

PMID- 8546604
TI  - Safety profile of thrombolytic drugs.

PMID- 8546606
TI  - Adjunctive therapy for myocardial infarction.

PMID- 8546605
TI  - [Left ventricular function in the acute phase of patients with myocardial
      infarction randomly treated with 750,000 or 1.5 million units of streptokinase].
AB  - PURPOSE: To compare the doses of 750,000 and 1.5 million units (U) of
      streptokinase (SK), relatively to the left ventricular (LV) systolic function
      analyzed through contrasted ventriculography. METHODS: We included 110 patients
      with acute myocardial infarction (AMI) within 6h of the onset (mean-age 60 years,
      83.6% men), that were randomized to receive 750,000U of SK in 15 min (55
      patients), or 1.5 million U in 30 min (55 patients). The study main goal was the
      comparison between the groups relatively to LV ejection fraction, global and
      regional shortening, obtained at the fifth day of the AMI. RESULTS: The 750,000
      and 1.5 million groups were homogeneous relatively to 15 analyzed variables.
      Relatively to the main goal of the study, it was found respectively: a) ejection
      fraction analysis (median): 64% and 60.5% for the total population (p = 0.25, 95%
      CI -2.7 to 10), 64% and 57.5% for anterior AMI (p = 0.2, 95% CI -3.6 to 16.3),
      65% and 65% for inferior AMI (p = 0.99, 95% CI -8.4 to 8.4); b) global shortening
      analysis: -2.53 and -2.66 for the total population (p = 0.3, 95% CI -0.47 to
      0.87), -2.27 and -2.53 for anterior AMI (p = 0.18, 95% CI -0.3 to 1.4), -1.82 and
      1.72 for inferior AMI (p = 0.9, 95% CI -0.82 to 0.75); c) regional shortening
      analysis: anterior AMI -2.6 and -2.67 (p = 0.47, 95% CI -0.7 to 1.5), inferior
      AMI -2.3 and -2.32 (p = 0.9, 95% CI -0.82 to 0.75). CONCLUSION: The dose of
      750,000U was as efficacious as the 1.5 million relatively to LV systolic
      function, one of the best survival predictors of short-medium and long-term
      survival post AMI.

PMID- 8546607
TI  - Care of the aged.

PMID- 8546608
TI  - The RACGP and the proposed trials in co-ordinated care.

PMID- 8546609
TI  - The QA&CE Program in the new triennium 1996-1998.

PMID- 8546610
TI  - Common skin, hair and nail problems during the first six months of life.
AB  - When an infant under 6 months of age presents to the family doctor with a skin,
      hair or nail problem, the evaluation process must determine whether the findings
      are physiologic and of no concern or due to a pathologic process. In addition to
      preventing unnecessary investigations and treatment, this distinction will enable
      the early assessment of those infants with pathologic processes that can involve
      structures other than the skin. The common causes (physiologic and pathologic) of
      those skin, hair and nail findings which present during the first 6 months of
      life will be discussed with the focus on the clinical features and differential
      diagnosis of each condition. Treatment will not be discussed. This is the first
      of three such articles.

PMID- 8546611
TI  - Neurological observations.
AB  - Family physicians generally find the neurological examination a problem because
      of its perceived length and complexity. But the neurological examination can be
      made both shorter and more informative by seeing it as commencing from the moment
      of first meeting the patient and continuing through the history taking and
      combining this with a focusing of the formal examination of relevant areas.

PMID- 8546612
TI  - Suspecting the obvious in rheumatology.
AB  - In rheumatological medicine taking an accurate history is essential. So too is
      the skill of observing a clinical sign, recognising its significance and then
      following through with an appropriate line of questioning. This article
      highlights some of the rheumatological signs that may be observed by a seemingly
      casual head to toe scan of a patient.

PMID- 8546613
TI  - Otitis externa. Presentation and management.
AB  - Otitis externa is a common condition presenting in both general and hospital
      practice. Diagnosis and treatment are usually straightforward; however
      appropriate management requires recognition of predisposing and precipitating
      factors, effective cleaning of the external auditory canal and administration of
      suitable topical or systemic medication or both. The aim of this article is to
      provide an overview of the clinical features and management of otitis externa
      with a discussion of the differential diagnosis.

PMID- 8546614
TI  - Sweet's syndrome associated with erythema nodosum.
AB  - The association between Sweet's syndrome and erythema nodosum in the same patient
      is rare. However, it is important that family physicians recognise how to
      differentiate these conditions clinically and histopathologically. A case is
      described with a combination of Sweet's syndrome and erythema nodosum, and
      appropriate treatment is discussed.

PMID- 8546615
TI  - Facial tics.
AB  - This short paper presents an approach to management of facial tics, which are
      rare in adults. Facial tics are usually progressive. If bilateral, the condition
      is usually 'benign essential blepharospasm'. If unilateral they are usually due
      to hemifacial spasm.

PMID- 8546616
TI  - Circumscribed pigmented lesions.
AB  - In this second article of common skin, hair, and nail problems during the first
      six months of life, issues related to pigmentation changes in the skin are
      addressed. These changes may be circumscribed or linear in appearance and either
      brown or blue.

PMID- 8546617
TI  - Don't get stung with the adrenergic blockers (beta or alpha)!

PMID- 8546618
TI  - Review of computer usage among RACGP members.
AB  - OBJECTIVE: To quantify the extent of, and attitude towards, computerisation in
      Australian general practice. DESIGN: In late 1993 a questionnaire was mailed to
      638 randomly selected members of the Royal Australian College of General
      Practitioners asking them about their experience of computerisation. One follow
      up mail out was carried out six weeks later. The results of the survey were
      collated and analysed by the investigators using a standard computer based
      software package. RESULTS: A total of 398 responses (62.4%) were received. 158
      (39.7%) are currently using, or have used a practice computer system; 31 of these
      (7.8% of the total) use a computerised patient record system. Computerised
      practices are more frequently RACGP Training Program or university teaching
      practices; in a rural locality; have a larger number of full time equivalent
      doctors working there; a larger gross annual practice income, and a non medical
      practice manager. Most respondents perceived computers as "useful now" in most
      areas of practice. CONCLUSIONS: The survey results suggest that computerisation
      in Australian general practice is less widespread than usually thought. Non
      computer users do not know enough about the benefits of computerisation to make
      an informed decision about computerising.

PMID- 8546619
TI  - Gastric acid-related disorders: GORD and peptic ulcer disease.
AB  - Gastro-oesophageal reflux disease (GORD) and peptic ulcer disease share similar
      clinical features, both have a high prevalence in the Australian community and
      both are associated with gastric acid secretion. In recent years there has been a
      considerable improvement in understanding of the pathogenesis of these
      conditions, leading to more effective therapy. The management of these disorders
      with particular reference to general practice will be reviewed.

PMID- 8546620
TI  - Practice tip. How to choose the right suture material.

PMID- 8546621
TI  - Hayfever (seasonal allergic rhinitis)

PMID- 8546622
TI  - Febrile child after visit to Solomon Islands.

PMID- 8546623
TI  - A case of Prinzmetal angina.

PMID- 8546624
TI  - Patient education. The snuffling infant.

PMID- 8546625
TI  - Musculoskeletal medicine tip. Spasmodic torticollis.

PMID- 8546626
TI  - Obstetric emergencies: their practical management.
AB  - Collapse in an obstetric patient may be due to any of the causes listed in Table
      1. If none of the specific treatments discussed are indicated the procedure
      should be: RESUSCITATE, TRANSFER AND DIAGNOSE--in that order.

PMID- 8546627
TI  - Heartsink revisited.

PMID- 8546628
TI  - Developments in treatment of metastatic melanoma.

PMID- 8546629
TI  - Doctors in court.

PMID- 8546630
TI  - Is rural practice so different?

PMID- 8546631
TI  - Rural general practice training.

PMID- 8546632
TI  - Antibiotics and contraceptives.

PMID- 8546633
TI  - Beating the drug habit.

PMID- 8546634
TI  - General practitioner obstetric practice in rural and remote Western Australia.
AB  - The objective of this study was to examine the practice of obstetrics by general
      practitioners in rural and remote areas of Western Australia (WA). A
      questionnaire was mailed to all rural and remote GPs in June, 1994. The response
      rate was 67%. Questionnaires asked GPs to self-report how many deliveries they
      had performed in the previous year and how many of those deliveries were by
      Caesarean section or assisted by forceps or ventouse. Comparisons were made with
      perinatal statistics for the entire State of WA. GPs reported an average of 28
      deliveries per year. The Caesarean section rate of 8% was lower than the rate of
      21% for all WA in 1993. Ventouse was used more often than forceps to assist the
      delivery of a baby. Intervention rates for ventouse, forceps and Caesarean
      section were lower in rural and remote areas of WA than the State as a whole;
      there was also less use of epidural analgesia. More than half of these GPs
      currently practising obstetrics hold the Dip RACOG or DRCOG. Medical indemnity is
      an increasing issue for many GPs. For 6 of the 7 country health regions, close to
      80% of women deliver within the health region in which they reside.

PMID- 8546635
TI  - The amniotic fluid embolism syndrome: 10 years' experience at a major teaching
      hospital.
AB  - A review of the syndrome of amniotic fluid embolism (AFE) was carried out over a
      10 year period, 1984-1993, at the Royal Women's Hospital, Brisbane. There were 9
      patients with AFE, of whom 2 died--this gave an incidence of fatal AFE of 3.37
      per 100,000 pregnancies at the hospital, in comparison with an incidence of 1.03
      per 100,000 pregnancies over a 27-year period in Australia. The study revealed no
      identifiable risk factors in the characteristics of the patient or her baby,
      labour and delivery. Three of the patients did not undergo labour and in 4 of the
      6 who did, the duration was less than 12 hours. The AFE syndrome could present
      before, during or after delivery; the common features were shock and respiratory
      distress, with coagulopathy occurring in 5 patients. Current views of
      predisposing factors, pathogenesis, diagnosis and management are discussed.

PMID- 8546636
TI  - Evaluation of a rapid enzyme immunoassay for detection of genital colonization of
      group B streptococci in pregnant women: own experience and review.
AB  - We have compared an enzyme immunoassay (ICON Step B, Hybritech) with cultures for
      demonstration of genital carriage of group B streptococci (GBS) in pregnant
      women, and studied the relationship between vaginal and rectal carriage of this
      organism. Pertinent literature has also been reviewed. Two hundred pregnant women
      at gestational week 17 were included. Swabs from the uterine cervix were tested
      for GBS by ICON Strep B immunoassay and ordinary cultures on blood agar.
      Additional swabs from the rectum were tested by cultures. The percentage of women
      with GBS in cervical secretions was 13.5% (27/200) by cultures and 4% (8/200) by
      the ICON Strep B immunoassay. The overall sensitivity of the immunoassay was
      7.4%, and the specificity 96.5%. In conclusion, the sensitivity of rapid enzyme
      immunoassays is too low for accurate screening of GBS in the genital tract of
      pregnant women.

PMID- 8546637
TI  - Second trimester colour Doppler imaging of the uterine artery: reproducibility of
      the resistance index.
AB  - Second trimester assessment of uterine blood flow has been advocated as a
      predictor of subsequent adverse perinatal outcome. The reproducibility of uterine
      artery resistance index, as assessed using colour Doppler imaging, was
      investigated. Two observers, both of whom were experienced in colour Doppler
      assessment of uterine artery flow velocity waveforms, performed the measurements.
      One-way analysis of variance was used to evaluate intraobserver variability and
      the limits of agreement method was used to determine the 95% prediction interval
      for interobserver differences. The intraobserver standard deviation was small for
      both observers. The limits of agreement for interobserver differences were wide (
      0.24, 0.16), similar in magnitude to those reported by other workers who assessed
      the uterine vessel using continuous wave Doppler. The poor reproducibility of the
      resistance index suggests that second trimester Doppler assessment of uterine
      artery flow velocity waveforms may be better described using other
      semiquantitative methods such as the presence or absence of a diastolic notch.

PMID- 8546639
TI  - Using glucose tolerance test results to predict insulin requirement in women with
      gestational diabetes.
AB  - This study was done to test the clinical impression that the result of the oral
      glucose tolerance test could be used to predict which patients with gestational
      diabetes did not need insulin therapy. If this was true, a full blood sugar
      profile assessment could be avoided in many of these women. The second analysis
      was to test the clinical impression that the fasting glucose level was the best
      predictor of insulin requirement in women with gestational diabetes. The results
      of the study showed that none of the 3 readings of the oral glucose tolerance
      test could be used to predict reliably which patients did not need insulin
      therapy. Hence, blood sugar profile assessment of all patients with gestational
      diabetes is still necessary. The receiver-operator characteristic curves also
      showed that the 2-hour postload glucose level during the 75 g load glucose
      tolerance test was a better predictor of insulin requirement than the fasting
      glucose level.

PMID- 8546638
TI  - Fetal fibronectin in the cervicovaginal fluid of women with threatened preterm
      labour as a predictor of delivery before 34 weeks' gestation.
AB  - Fetal fibronectin (fFN) is an extracellular matrix protein found at the junction
      between fetal and maternal tissue. It has been hypothesized that fFN is released
      into cervicovaginal fluid prior to the onset of preterm labour and during
      episodes of threatened preterm labour (TPL). In the present study fFN was present
      in the cervicovaginal fluid of 31% (11/36) of patients with TPL. The presence of
      fFN was found to be predictive of delivery prior to 34 weeks' gestation in 36
      patients presenting with TPL and intact membranes (sensitivity 100%, specificity
      81%). Eleven patients had a positive fFN assay and 5 delivered before 34 weeks
      (positive predictive value (PPV) 46%). Twenty-five patients had a negative fFN
      result and none were delivered before 34 weeks (negative predictive value (NPV)
      100%). Patients presenting with TPL who are fFN positive would be ideal
      candidates for intervention trials of tocolytics. It may be possible to delay or
      avoid immediate tocolysis and interhospital transfer in patients with a negative
      fFN immunoassay.

PMID- 8546640
TI  - Intrapartum detection of a macrosomic fetus: clinical versus 8 sonographic
      models.
AB  - The purpose of this study was to determine whether clinical or sonographic models
      have 1) the highest accuracy in differentiating newborns with birth-weights > or
      = 4,000 g (macrosomia) versus < or = 3,999 g, and 2) among macrosomics which
      method of predicting birth-weight has the lowest percentage error. Prospectively,
      602 consecutive parturients at term had a clinical estimate of birth-weight
      followed by sonographic measurement of fetal parts. The sonographic prediction of
      birth-weight was derived using 8 different models that utilize either 1
      measurement or a combination of 2 to 4 parameters. The incidence of macrosomia
      was 11.1% (67 of 602). Analysis of ROC curves indicated that clinical predictions
      (w = 0.85) were significantly better than 4 of the 8 sonographic models. The mean
      standardized absolute error among macrosomic newborns is significantly lower when
      predictions are derived clinically (99 +/- 70 g/kg) than using 1 or 2 fetal
      parts. Sonographic assessment of birth-weight is not significantly more accurate
      in the detection of a macrosomic fetus than clinical predictions.

PMID- 8546641
TI  - Shoulder dystocia. Report of 2 cases and review of the literature.
AB  - Shoulder dystocia, or impacted shoulders is an infrequently encountered obstetric
      emergency. Despite various risk factors identified by investigators, the
      occurrence of shoulder dystocia is difficult to predict. Two cases of severe
      shoulder dystocia managed personally by the author are presented. These cases
      illustrate some of the important issues regarding prediction of shoulder dystocia
      and the need to begin a series of well-tested manoeuvres immediately, to
      successfully deliver the baby.

PMID- 8546642
TI  - External cephalic version at a military teaching hospital: predictors of success.
AB  - The purpose of this prospective study was to analyze our experience with external
      cephalic version under tocolysis. This included an expected (1) high success rate
      of version, (2) infrequent occurrence of reversion, (3) reduction in the
      incidence of intrapartum breech presentation, avoiding the need for Caesarean
      delivery, and (4) predictors of success in our series. The study spanned the
      period from 1985 to 1993, enrolling 113 subjects who presented to our OB/GYN
      Department with any type of breech presentation at 37 weeks' gestation or greater
      and met the following criteria: (1) absence of labour or ruptured membranes, (2)
      singleton pregnancy, (3) absence of medical or obstetrical complications and
      amniotic fluid index of greater than 8 cm. After a reassuring fetal assessment,
      IV terbutaline was given prior to an attempt at version. The results revealed a
      46% (53 or 113) version success rate with a 4% (2 of 53) reversion within a week
      after procedure. There was a 2% (2 of 113) complication rate, with 1 being a
      minor incident of fetal bradycardia that responded easily to intrauterine
      resuscitation. One major complication occurred with placental abruption during
      the attempt, which required immediate Caesarean delivery. Predictors of success
      in our series included: multiparity, fundal/posterior placenta, and fetal head
      and spine on the corresponding side of the maternal sagittal plane. External
      cephalic version in a controlled setting can be a safe procedure for residents in
      training that lowers Caesarean delivery rate for breech presentation.

PMID- 8546643
TI  - Delayed-interval delivery in a quadruplet pregnancy: the use of transperineal
      ultrasound and cervical cerclage.

PMID- 8546644
TI  - Obstetric experience of female medical practitioners as patients.
AB  - The objective was to investigate the obstetric experience of South Australian
      medical practitioners, and in addition, to assess whether the reported increase
      in adverse pregnancy outcomes among medical practitioners in America occurs in
      South Australia. A population-based postal survey of the entire registered female
      medical population of South Australia was carried out. Comparison was made with
      randomly selected individually matched pregnant South Australian control women.
      No significant increase in any complications was found when compared with a case
      controlled group matched for age, parity, year of delivery, and social class.
      There was a strongly significant increase in their interest in pregnant women and
      empathy with the difficulties of pregnancy after their own deliveries. The
      reported increase in complications in American women may be due to the working
      conditions of those studied. Further assessment of obstetric outcome should
      consider the individual women's working conditions, including stress. The South
      Australian group in general reported more difficulties with the postpartum period
      than the pregnancy itself, and this is the area where more research, and
      practical assistance should be concentrated.

PMID- 8546645
TI  - Relationships between doctors and patients in obstetrics and gynaecology.

PMID- 8546646
TI  - Sexuality in Nigerian pregnant women: perceptions and practice.
AB  - The sexual behaviour and beliefs of 440 pregnant women from South-eastern Nigeria
      were investigated. The mean frequency of sexual intercourse during pregnancy (1.5
      times per week) was less than that before pregnancy (2.3 times per week). The
      husband was the main initiator of sexual activity (41.6%), while the wife only
      rarely did so (2.7%). 44.3% of the respondents believed that sexual intercourse
      during pregnancy widens the vagina and facilitates labour; 34.8% that it improves
      fetal well-being; 30.2% that it caused abortion in early pregnancy while 21.1%
      had no knowledge of any repercussions of sexual intercourse in pregnancy. Coitus
      during pregnancy was always painful in 22.7% of the respondents; was always
      gratifying in 46.1%; was functional in 49.3% and helped to keep the husband
      around, also in 49.3% of the respondents. The majority of the respondents (83.4%)
      considered that coitus should not be stopped during pregnancy. Whereas 19.3% of
      the respondents believed that sexual frequency should be increased during
      pregnancy, 73.9% considered otherwise, and 63.6% actually felt it should be
      reduced. Findings from this study suggest a 'mixed-feeling' effect with a tilt
      towards a positive attitude to sexuality in pregnancy. Restriction should not be
      imposed on sexual activity during a normal pregnancy to enhance marital harmony.

PMID- 8546648
TI  - Follow-up of patients with gynaecological cancer.

PMID- 8546647
TI  - Quality of life assessment in gynaecological cancer patients.
AB  - The feasibility of quality of life (QOL) assessment in a heterogeneous group of
      gynaecological cancer patients undergoing chemotherapy was determined. All new
      patients being prescribed cytotoxic chemotherapy were asked to complete a
      modified QOL assessment tool. The elected assessment tool is the Functional
      Assessment Cancer Therapy-General (FACT-G) tool, comprising 33 questions under 5
      broad categories: physical well-being, social well-being, relationship with
      doctor, emotional well-being and functional well-being. Raw scores were
      calculated and then transformed to a 0-100 scale. Twenty eight patients received
      a total of 75 treatment cycles of chemotherapy. Four patients were not offered
      the assessment due to language difficulties. All patients offered the test
      satisfactorily completed the test to allow statistical analysis. The average
      number of chemotherapy courses received was 2.5 (range: 1-6). Of a total possible
      2,475 study items (33 items x 75 cycles), 240 items were not answered (10%). Of
      these 240 unanswered items, 2 items (#14 and #15) comprised 38%. The mean
      transformed score for physical well-being was 32 (SE 2.5), for social well-being
      the mean transformed score was 50 (SE 1.7), relationship with doctor 86 (SE 2.4),
      emotional well-being 41 (SE 2) and functional well-being was 54 (SE 2.6). The
      assessment of QOL indices in gynaecological cancer patients undergoing
      chemotherapy is feasible. Further research needs to determine the optimal QOL
      tool for this patient population.

PMID- 8546649
TI  - Repair of the perineal defect after radical vulvar surgery: direct closure versus
      skin flaps reconstruction. A retrospective comparative study.
AB  - From 1987 to 1990, 72 consecutive patients with primary untreated vulvar cancer
      underwent radical vulvar surgery with skin flaps reconstruction of the perineal
      defect. Postoperative complications, anatomical and functional results of this
      group of patients were compared with those of an historical control group of 77
      patients submitted, at the same institution, to radical vulvectomy without
      reconstructive procedure from 1982 through 1986. The time of operation was
      significantly longer (180 minutes +/- 15 versus 120 minutes +/- 20) (p = 0.05)
      for patients submitted to the reconstructive procedure, while there was no
      statistically significant difference in intraoperative blood loss and hospital
      stay between the 2 groups. In comparison with direct closure, reconstructive
      procedures resulted in a significant lower rate of wound dehiscences (26% versus
      64%) (p = 0.0001), vaginal introitus stenosis (2 versus 8) (p = 0.0001), sexual
      dysfunction (10% versus 50%) (p = 0.0001) and misdirection of the urinary stream
      (1 versus 5) (p = 0.001). It was concluded that skin flaps reconstruction is
      simple, reduces postoperative morbidity, and provides better anatomical and
      functional results than direct closure of the perineal defect.

PMID- 8546650
TI  - The effect of dance training on menstrual function in collegiate dancing
      students.
AB  - A total of 98 dancing students from a collegiate school of dancing were studied
      through interview using a highly structured questionnaire to elicit details of
      the duration and intensity of dance training, menstrual patterns and
      musculoskeletal injuries sustained during training; 70 (72%) of these dancing
      students were eumenorrhoeic, while 15 (15.4%) had oligomenorrhoea. Thirteen
      (13.4%) either had amenorrhoea for over 90 days at the time of the study, or were
      on hormonal treatment because of amenorrhoea for over 3 months in the past 1
      year. Those who were amenorrhoeic had longer training hours per week when
      compared with eumenorrhoeic and oligomenorrhoeic students. Both oligomenorrhoeic
      and amenorrhoeic students had a lower body mass index (18.25 kg/m2 and 18.26
      kg/m2 versus 19.45 kg/m2, p < 0.01), and a higher incidence of musculoskeletal
      injuries and chronic orthopaedic problems compared to eumenorrhoeic ones. Ballet
      students had a higher incidence of menstrual dysfunction and musculoskeletal
      injuries as compared to classic Chinese dance, modern dance and musical theatre
      dance students as well as a significantly lower average body mass index. These
      data suggest a proportional correlation between menstrual dysfunction and
      proneness to musculoskeletal injuries in training, which could be explained by a
      hormonal mechanism.

PMID- 8546651
TI  - The efficacy of hysteroscopy: a comparison of women presenting with infertility
      versus other gynaecological symptoms.
AB  - The aim of this study was to compare the relative efficacy of hysteroscopy as a
      management tool in the routine initial assessment of women presenting for
      investigation of infertility with women presenting for investigation of other
      general gynaecological symptoms for which it is routinely performed. The results
      of 400 consecutive completed hysteroscopies performed during the primary
      investigation of infertility are compared with 400 consecutive completed
      hysteroscopies undertaken in the investigation of women with other gynaecological
      symptoms. Abnormalities were detected in 12.3% of the 800 hysteroscopies.
      Significantly less of the infertility group demonstrated abnormality (8.8%)
      compared to the general gynaecological group (15.8%) (p = 0.0034). There was no
      difference in the detection rate between primary and secondary infertility. In
      patients undergoing the procedure for infertility, the results of the
      hysteroscopy led to an alteration in management in 5.8% of the entire group and
      in 65.7% of those in whom an abnormality was detected. In patients undergoing the
      procedure for general gynaecological symptoms, the results of the hysteroscopy
      led to an alteration in management in 14.5% of the total group and in 97.2% of
      those in whom an abnormality was detected (p < 0.0001). Structural abnormality
      correlated with the presence of histological abnormality in 97.2% of cases. In
      infertile women, the use of hysteroscopy is supported as part of a comprehensive
      assessment of female reproductive anatomy.

PMID- 8546652
TI  - Use of prophylactic tinidazole to avoid the serious infections associated with
      total abdominal hysterectomy.

PMID- 8546653
TI  - Listeria septicaemia in a young healthy pregnant woman.

PMID- 8546654
TI  - Acute hypoglycaemic coma--a rare, potentially lethal form of early onset Sheehan
      syndrome.
AB  - This case emphasizes the importance of intensive obstetric management that is
      required when confronted with prolonged postpartum haemorrhage. Anticipation of
      the possibility of acute hypoglycaemic coma as an initial manifestation of
      Sheehan syndrome and prompt recognition may prevent disastrous consequences,
      including maternal death.

PMID- 8546655
TI  - Insulin-dependent diabetes mellitus presenting as diabetic ketoacidosis in
      pregnancy.

PMID- 8546656
TI  - Amnion rupture in the second trimester.
AB  - Two cases of amnion rupture are presented in 'low-risk' pregnancies. One case
      ended in fetal death in utero at 21 weeks. The other resulted in the preterm
      delivery of an otherwise normal male with mild amniotic band syndrome.

PMID- 8546657
TI  - Successful outcome with serial amniocenteses for polyhydramnios complicating
      cystic adenomatoid malformation of the lung.
AB  - Hydrops fetalis secondary to congenital cystic adenomatoid malformation of the
      fetal lung is almost invariably a lethal condition. This poor prognosis may be
      attributed to the combined effects of tissue compression from the thoracic space
      occupying lesion and premature delivery of a hydropic baby following rupture of
      the membranes in the presence of polyhydramnios. We describe a successful outcome
      with serial amniocenteses. Partial in utero resolution of the lung lesion with
      complete return to normal of the aberrant liquor volume was documented, and a
      live infant was delivered at term.

PMID- 8546659
TI  - Is the fibroid a uterus?

PMID- 8546658
TI  - Blood loss in termination of early pregnancy with mifepristone and gemeprost.
AB  - The combination of an antiprogestogen with prostaglandin has been shown to be an
      effective alternative to surgical procedures for pregnancy termination in the
      first 49 days of amenorrhoea and has been available in France since late 1988.
      Mifepristone when used alone caused poor efficacy with unacceptable vaginal
      bleeding. The addition of a prostaglandin analogue (sulprostone, gemeprost)
      produced acceptable efficacy with less bleeding. The present study provides a
      quantitative assessment of blood loss in a sample of 20 women undergoing medical
      termination of early pregnancy (amenorrhoea < or = 49 days). Vaginal bleeding
      occurred between days 3 and 15 of commencing therapy. The median number of days
      of bleeding was 4 with a median blood loss of 91.5 mL. The mean blood loss was
      136.8 mL (+/- SD 159.2) but this did not adversely affect the hemoglobin level in
      the volunteers. Most patients describe the experience as that similar to a heavy
      period and viewed the procedure positively especially since they are spared the
      anaesthetic risks and hospitalization attendant with surgical abortion. Caution
      is still however advised as there may be the occasional subject with excessive
      haemorrhage (as in this study where one woman bled a total of 761.4 mL) and close
      supervision by a physician is essential.

PMID- 8546660
TI  - Adenomyosis following endometrial rollerball ablation.
AB  - Two cases of adenomyosis following endometrial ablation using a rollerball
      electrode are reported. In both patients the endometrial ablation was performed
      for severe menorrhagia in the absence of uterine pathology. The endometrium was
      not prepared. After the operation, the women had persistent light menstruation
      for 7 to 9 months which then became heavy. They also developed progressive
      dysmenorrhoea and uterine enlargement. Abdominal hysterectomy was subsequently
      performed and adenomyosis was confirmed on histological examination. Prior
      endometrial preparation with hormone therapy may reduce the risk of incomplete
      destruction of the endometrium and therefore reduce the risk of postablation
      adenomyosis.

PMID- 8546661
TI  - von Willebrand disease: a rare cause of puberty menorrhagia.
AB  - A 13-year-old girl with a family history of epistaxis presented with pubertal
      menorrhagia necessitating multiple blood transfusions. Her coagulation profile
      confirmed the diagnosis of Von Willebrand disease. The menorrhagia was controlled
      by cyclical use of oestrogen progestogen combination drugs. The important
      clinical implication of this case is that the patient with adolescent menorrhagia
      may have an underlying coagulation disorder, which can successfully be managed by
      hormones.

PMID- 8546662
TI  - Early uterine prolapse following colponeedle suspension.
AB  - The association of retropubic colposuspension for the treatment of urinary stress
      incontinence with genital prolapse has been reported previously. Described here
      is a case of an 83-year-old patient who had a colponeedle suspension and was
      readmitted because of genital prolapse 3 weeks after surgery. This case
      emphasizes the need for proper evaluation of the whole pelvic floor prior to any
      surgical treatment for urinary incontinence, and addition of appropriate surgical
      measures aimed to avoid later genital prolapse, if necessary.

PMID- 8546663
TI  - Fibroid arising in a mullerian duct remnant and presenting as a pelvic mass in a
      patient with vaginal agenesis: an unusual finding.
AB  - We report a case of vaginal agenesis associated with a large fibroid arising from
      a Mullerian duct remnant. Vaginal agenesis is rare and infrequently encountered
      by gynaecologists. Its association with a pelvic mass is even more uncommon, and
      a medline search by the authors has failed to uncover another reported case. We
      provide the clinical details of this case and discuss the differential diagnoses.

PMID- 8546664
TI  - Tuberculous uteroenterocutaneous fistula--a rare post-caesarean complication.
AB  - A case of uteroenterocutaneous fistula which developed after lower segment
      Caesarean section is described. A total abdominal hysterectomy with removal of a
      tuboovarian mass with excision of the fistulous tract and repair of a small gut
      fistula were performed. The tuberculous aetiology of this fistula was established
      after surgery by a positive endometrial culture of acid fast bacilli and the
      demonstration of epithelioid granulomas in the surgical specimen.
      Antituberculosis therapy was started and the postoperative recovery was
      uneventful. The description of the nature of the fistula, its rarity and its
      presence in a woman with unimpaired fertility are discussed.

PMID- 8546665
TI  - Vulval lymphangioma: the cause still a mystery?

PMID- 8546666
TI  - Angiolymphoid hyperplasia with eosinophilia of the vulva.
AB  - Vulvar angiolymphoid hyperplasia with eosinophilia is a rare benign itchy
      vascular lesion that, because of its nonspecific clinical features, requires
      biopsy for accurate diagnosis. Surgical excision is the preferred method of
      treatment.

PMID- 8546667
TI  - The use of cervicography in the follow-up of cervical intraepithelial neoplasia
      treated by CO2 laser.
AB  - After treatment for cervical intraepithelial neoplasia (CIN) the follow-up of
      patients would be simplified if colposcopy could be safely omitted. A study of 50
      patients was performed to determine the feasibility of such an approach. Cervical
      cytology, cervicography and colposcopy, with or without biopsy, was performed in
      each patient. From the results the following criteria for colposcopy were
      adopted: (a) patients thought to have CIN on cytology or cervicography, (b)
      inadequate cervicography picture (vagina covering cervix or poor quality
      photography), (c) high-risk factors present (immunosuppression, after cone
      biopsy, postmenopausal). In this study the number of colposcopies would have been
      reduced from 50 to 11 if these criteria were adopted. Cervical cytology combined
      with cervicography is a reasonable alternative to colposcopy and we feel this is
      a technique worth pursuing for the follow-up of patients treated for CIN.

PMID- 8546668
TI  - Severe twin-twin transfusion syndrome: current management concepts.

PMID- 8546669
TI  - Sacrospinus colpopexy.

PMID- 8546670
TI  - Small bowel incarceration after laparoscopically-assisted vaginal hysterectomy--a
      preventable complication?

PMID- 8546671
TI  - Dual bradykinin B2 receptor signalling in A431 human epidermoid carcinoma cells:
      activation of protein kinase C is counteracted by a GS-mediated stimulation of
      the cyclic AMP pathway.
AB  - Cell membranes of the human epidermoid cell line A431 express classical
      bradykinin (BK) B2 receptors, as assessed by [3H]BK binding studies. Furthermore,
      stimulation by BK induced a time-dependent modulation of protein kinase C (PKC)
      activity in A431 cells: a rapid activation (t1/2 approximately 1 min) is followed
      by a slow inhibition (t1/2 approximately 20 min) of PKC translocation measured by
      [3H]phorbol 12,13-dibutyrate binding. In addition, BK stimulated both adenylate
      cyclase activity in A431 membranes and accumulation of intracellular cyclic AMP
      (cAMP) in intact cells in a retarded manner. A possible BK-induced activation of
      the cAMP pathway mediated via PKC, phospholipase D, prostaglandins or
      Ca2+/calmodulin was excluded. A 35 kDa protein was found in A431 membranes to be
      specifically phosphorylated in the presence of both BK and protein kinase A
      (PKA). An anti-alpha s-antibody, AS 348, abolished stimulation of adenylate
      cyclase activity in response to BK, cholera toxin and isoprenaline, strongly
      suggesting the involvement of Gs proteins in the BK action. The BK-activated cAMP
      signalling system might be important for the observed inactivation of PKC slowly
      evoked by BK: the BK-induced rapid activation of PKC is decreased by dibutyryl
      cAMP, and the slow inhibition of PKC is prevented by an inhibitor of PKA,
      adenosine 3':5'-monophosphothioate (cyclic, Rp isomer). The inhibition of PKC
      translocation might be exerted directly at the level of PKC activation, since
      stimulation of phosphoinositide hydrolysis by BK was affected by neither
      dibutyryl cAMP nor forskolin. Thus our results provide the first evidence that
      A431 cells BK is able to activate two independent signal-transduction pathways
      via a single class of B2 receptors but two different G proteins. The lagging
      stimulation of the cAMP signalling pathway via Gs might serve to switch off PKC,
      which is rapidly activated via Gq-mediated stimulation of phosphoinositide
      hydrolysis.

PMID- 8546672
TI  - The mitogen-activated protein kinase pathway in rat islets of Langerhans: studies
      on the regulation of insulin secretion.
AB  - The expression of mitogen-activated protein kinases (MAPKs) and MAPK kinases
      (MEKs) in rat islets of Langerhans and the involvement of MAPKs in regulated
      insulin secretion were examined. Two major isoforms of both MEK (45 and 46 kDa)
      and MAPK (42 and 44 kDa) were detected in rat islets and shown to be localized to
      insulin-secreting beta cells by detection of their expression in the beta cell
      line MIN6. The tyrosine phosphatase inhibitor sodium pervanadate, and, to a
      lesser extent, the serine/threonine phosphatase inhibitor okadaic acid,
      stimulated MAPK phosphorylation, as assessed by a shift in its electrophoretic
      mobility and by increased phosphotyrosine immunoreactivity of immunoprecipitated
      MAPK. The increase in MAPK phosphorylation stimulated by sodium pervanadate was
      not coupled to an increase in MAPK activity, but okadaic acid, either alone or in
      the presence of sodium pervanadate, caused an increase in myelin basic protein
      phosphorylation by MAPK. Neither okadaic acid nor sodium pervanadate, either
      individually or combined, stimulated insulin secretion. 4 beta-phorbol myristate
      acetate stimulated an increase in phosphorylation of the 42 kDa isoform of MAPK
      (erk2) in human umbilical vein endothelial cells, but neither it nor glucose
      affected either the phosphorylation state of islet erk2 or the activities of
      immunoprecipitated islet MAPKs. These results provide evidence for the presence
      of a regulated MAPK pathway in adult rat islets, but our data suggest that MAPK
      activation alone is not a sufficient stimulus for insulin secretion.

PMID- 8546673
TI  - Phosphatidylinositol 3-kinase acts at an intracellular membrane site to enhance
      GLUT4 exocytosis in 3T3-L1 cells.
AB  - Glucose transporters (GLUTs) are continuously recycled in 3T3-L1 cells and so
      insulin, through its action on phosphatidylinositol 3-kinase (PI 3-kinase), could
      potentially alter the distribution of these transporters by enhancing retention
      in the plasma membrane or acting intracellularly to increase exocytosis, either
      by stimulating a budding or a docking and fusion process. To examine the site of
      involvement of PI 3-kinase in the glucose transporter recycling pathway, we have
      determined the kinetics of recycling under conditions in which the PI 3-kinase
      activity is inhibited by wortmannin. Wortmannin addition to fully insulin
      stimulated cells induces a net reduction of glucose transport activity with a
      time course that is consistent with a major effect on the return of internalized
      transporters to the plasma membrane. The exocytosis of GLUT1 and GLUT4 is reduced
      to very low levels in wortmannin-treated cells (approximately 0.009 min-1), but
      the endocytosis of these isoforms is not markedly perturbed and the rate
      constants are approx. 10-fold higher than for exocytosis (0.099 and 0.165 min-1,
      respectively). The slow reduction in basal activity following treatment with
      wortmannin is consistent with a wortmannin effect on constitutive recycling as
      well as insulin-regulated exocytosis. PI 3-kinase activity that is precipitated
      by anti-phosphotyrosine, anti(-)[insulin receptor substrate 1 (IRS1)] and anti
      alpha-p85 antibodies show the same level of insulin-stimulated activity,
      approximately 0.5 pmol/20 min per dish of 3T3-L1 cells. Since the activities
      precipitated by all three antibodies are similar, it seems unlikely that a second
      insulin receptor substrate, IRS2, contributes significantly to the insulin
      signalling observed in 3T3-L1 cells. To examine whether insulin targets PI 3
      kinase to intracellular membranes we have carried out subcellular fractionation
      studies. These suggest that nearly all the insulin-stimulated PI 3-kinase
      activity is located on intracellular, low-density, membranes. In addition, the
      association of PI 3-kinase with IRS1 appears to partially deplete the cytoplasm
      of alpha-p85-precipitatable activity, suggesting that IRS1 may redistribute PI 3
      kinase from the cytoplasm to the low-density microsome membranes. Taken together,
      the trafficking kinetic and PI 3-kinase distribution studies suggest an
      intracellular membrane site of action of the enzyme in enhancing glucose
      transporter exocytosis.

PMID- 8546674
TI  - Glucose transport and GLUT4 protein distribution in skeletal muscle of GLUT4
      transgenic mice.
AB  - The aim of the present investigation was to determine whether the subcellular
      distribution and insulin-stimulated translocation of the GLUT4 isoform of the
      glucose transporter are affected when GLUT4 is overexpressed in mouse skeletal
      muscle, and if the overexpression of GLUT4 alters maximal insulin-stimulated
      glucose transport and metabolism. Rates of glucose transport and metabolism were
      assessed by hind-limb perfusion in GLUT4 transgenic (TG) mice and non-transgenic
      (NTG) controls. Glucose-transport activity was determined under basal (no
      insulin), submaximal (0.2 m-unit/ml) and maximal (10 m-units/ml) insulin
      conditions using a perfusate containing 8 mM 3-O-methyl-D-glucose. Glucose
      metabolism was quantified by perfusing the hind limbs for 25 min with a perfusate
      containing 8 mM glucose and 10 m-units/ml insulin. Under basal conditions, there
      was no difference in muscle glucose transport between TG (1.10 +/- 0.10 mumol/h
      per g; mean +/- S.E.M.) and NTG (0.93 +/- 0.16 mumol/h per g) mice. However, TG
      mice displayed significantly greater glucose-transport activity during submaximal
      (4.42 +/- 0.49 compared with 2.69 +/- 0.33 mumol/h per g) and maximal (11.68 +/-
      1.13 compared with 7.53 +/- 0.80 mumol/h per g) insulin stimulation.
      Nevertheless, overexpression of the GLUT4 protein did not alter maximal rates of
      glucose metabolism. Membrane purification revealed that, under basal conditions,
      plasma-membrane (approximately 12-fold) and intracellular-membrane (approximately
      4-fold) GLUT4 protein concentrations were greater in TG than NTG mice. Submaximal
      insulin stimulation did not increase plasma-membrane GLUT4 protein concentration
      whereas maximal insulin stimulation increased this protein in both NTG (4.1-fold)
      and TG (2.6-fold) mice. These results suggest that the increase in insulin
      stimulated glucose transport following overexpression of the GLUT4 protein is
      limited by factors other than the plasma-membrane GLUT4 protein concentration.
      Furthermore, GLUT4 overexpression is not coupled to glucose-metabolic capacity.

PMID- 8546675
TI  - Rapid identification of compounds with enhanced antimicrobial activity by using
      conformationally defined combinatorial libraries.
AB  - We have combined the strength of our synthetic combinatorial library approach for
      the rapid identification of highly active compounds with prior knowledge of the
      relationship between the antimicrobial activities of individual peptides with
      specific induced conformations in order to identify new peptides with enhanced
      activity relative to a starting known antimicrobial sequence. In the current
      study, conformationally defined combinatorial libraries were generated based on
      an 18-mer antimicrobial peptide known to be induced into an alpha-helical
      conformation in a lipidic environment. Not only were novel sequences readily
      identified with 10-fold increases in activity, but detailed information about the
      structure-activity relationships of the peptides studied was also obtained during
      the deconvolution process. By using circular dichroism spectroscopy it was found
      that the individual 18-mer peptides could be induced into alpha-helical
      conformations on interaction with the cell lipid layer and/or sialic acids, which
      could result in bacterial cell lysis due to perturbation of the lipid packing of
      the cell wall.

PMID- 8546676
TI  - A single gene encodes two different transcripts for the ADP-glucose
      pyrophosphorylase small subunit from barley (Hordeum vulgare).
AB  - ADP-glucose pyrophosphorylase (AGPase), a heterotetrameric enzyme composed of two
      small and two large subunits, catalyses the first committed step of starch
      synthesis in plant tissues. In an attempt to learn more about the organization
      and expression of the small-subunit gene of AGPase, we have studied the small
      subunit transcripts as well as the structure of the gene encoding these
      transcripts in barley (Hordeum vulgare L. cv. Bomi). Two different transcripts
      (bepsF1 and blps14) were identified: bepF1 was abundantly expressed in the
      starchy endosperm but not in leaves, whereas blps14 was isolated from leaves but
      was also found to be present at a moderate level in the starchy endosperm. The
      sequences for the two transcripts are identical over approx. 90% of the length,
      with differences being confined solely to their 5' ends. In blps14, the unique 5'
      end is 259 nt long and encodes a putative plastid transit peptide sequence. For
      the 178-nt 5' end of bepsF1, on the other hand, no transit peptide sequence could
      be recognized. A lambda clone that hybridized to the AGPase transcripts was
      isolated from a barley genomic library and characterized. The restriction map has
      suggested a complex organization of the gene, with alternative exons encoding the
      different 5' ends of the two transcripts followed by nine exons coding for the
      common part of the transcripts. The sequence of a portion of the genomic clone,
      covering the alternative 5'-end exons as well as upstream regions, has verified
      that both transcripts are encoded by the gene. The results suggest that the small
      subunit gene of barley AGPase transcribes two different mRNAs by a mechanism
      classified as alternative splicing.

PMID- 8546677
TI  - The organization of the human GSTP1-1 gene promoter and its response to retinoic
      acid and cellular redox status.
AB  - High levels of expression of GSTP1-1 are associated with cell proliferation,
      embryogenesis and malignancy. Given the role of glutathione S-transferase (GST)
      in detoxication, it is possible that GSTP1-1 evolved specifically to protect
      proliferating cells and share regulatory mechanisms with other cellular genes
      which are involved in cell division and tumorigenesis. We have previously shown
      that the expression of GSTP1 is suppressed by retinoic acid (RA) in the presence
      of the retinoic acid receptor (RAR) as a result of decreased transcription from
      its promoter. Through deletion analysis, we show here that the RA-RAR-dependent
      repression is mediated by the region -73 to +8. Further mutation analysis of this
      region indicates that the DNA sequence required for RA-RAR-dependent repression
      co-localizes with a consensus activator protein-1 (AP1) site essential for the
      promoter activity. The degree of repression correlates with the residual activity
      of the AP1 site. There are two adjacent G/C boxes. The one immediately downstream
      from the AP1 site is not essential for the promoter activity, but mutation of the
      second, further downstream, impairs the promoter. On the other hand, mutation of
      either of these two G/C boxes has little effect on RA-RAR suppression. We also
      show that the expression of GSTP1 is regulated by the redox status of the cell.
      Using the chloramphenicol acetyltransferase assay system, we have demonstrated
      that treatment with H2O2 induced transcription from the promoter and that this
      effect can be blocked by pre-incubation with N-acetylcysteine (NAC). It was shown
      that the induction by H2O2 is mediated by trans-acting factor NF-kappa B (nuclear
      factor kappa B), via a putative NF-kappa B site, 'GGGACCCTCC', located from -96
      to -86. Co-transfection with an NF-kappa B (p65) expression construct increased
      the promoter activity, an effect which could be blocked by co-transfection with
      an I kappa B (MAD-3) expression construct. Deletion of the NF-kappa B site
      abolished the effect of both H2O2 and co-transfection of NF-kappa B.
      Interestingly, NAC is also an inducer for GSTP1. The effect of NAC was shown to
      be mediated largely by the AP1 site, since mutation of this site abolished the
      induction by NAC.

PMID- 8546678
TI  - 1,10-Phenanthroline stimulates internucleosomal DNA fragmentation in isolated rat
      liver nuclei by promoting the redox activity of endogenous copper ions.
AB  - Isolated rat-liver nuclei were incubated with a series of membrane-permeable
      metal-ion-complexing agents and examined for DNA damage. Of the reagents tested,
      only 1,10-phenanthroline (OP) and neocuproine (NC) were found to induce DNA
      fragmentation. Agarose-gel electrophoresis of the DNA fragments generated in the
      presence of OP revealed internucleosomal cleavage, which is widely considered to
      be a hallmark for the enzymic DNA digestion that occurs during apoptosis.
      Ascorbate, particularly in the presence of hydrogen peroxide, increased the
      levels of fragmentation induced by OP. As well as undergoing fragmentation, the
      DNA from nuclei was also found to contain 8-hydroxydeoxyguanosine, which
      indicates attack (oxidation) by the hydroxyl radical. Complementary experiments
      in vitro involving ESR determinations of hydroxyl radical formation and
      measurements of DNA oxidation under biomimetic conditions demonstrated that Cu2+,
      but not Fe3+, forms a complex with either OP or NC (but not the other complexing
      agents tested) that stimulates hydroxyl radical formation and DNA damage in the
      presence of hydrogen peroxide and ascorbate. It is therefore proposed that OP in
      the nuclei incubations binds to Cu2+, which exists naturally in chromosomes,
      forming a complex that promotes hydroxyl-radical-dependent DNA fragmentation.
      These findings demonstrate the promotion of hydroxyl-radical-mediated DNA damage
      by endogenous Cu2+ and, perhaps more significantly, demonstrate that the
      internucleosomal DNA 'laddering' that is often used as an indicator of apoptosis
      may also result from DNA fragmentation by non-enzymic processes.

PMID- 8546680
TI  - ATP-regulated activity of the plasmin-streptokinase complex: a novel mechanism
      involving phosphorylation of streptokinase.
AB  - Streptokinase, an extracellular protein produced by Streptococci, is capable of
      activating the human fibrinolytic zymogen plasminogen. The rate of amidolytic
      activity of the plasminogen-streptokinase complex is greatly diminished by
      micromolar concentrations of ATP and heparin oligosaccharides. In addition, the
      plasminogen activator activity of the plasminogen-streptokinase complex is also
      inhibited by these effectors. ATP and heparin oligosaccharides show structural
      similarity, suggesting that the inhibition is caused by binding of these
      molecules to a common newly formed binding pocket in streptokinase, which appears
      after interaction with plasminogen. Addition of the bivalent cations Ca2+ and
      Mg2+ reverses the inhibition caused by ATP and heparin. In the presence of ATP
      and bivalent cations, the complex between plasminogen and streptokinase develops
      an autophosphorylating activity whose target is the sequence LTSRPAHG in the 4.5
      kDa streptokinase N-terminal peptide, which is an early autolysis peptide. This
      streptokinase N-terminal peptide, which is essential for streptokinase activating
      activity, may serve, once phosphorylated, in mechanisms related to the
      pathogenicity of Streptococci. These studies suggest a critical role for
      plasminogen in regulating the activity of the streptokinase molecule.

PMID- 8546681
TI  - Activation of human liver 3 alpha-hydroxysteroid dehydrogenase by
      sulphobromophthalein.
AB  - Human liver contains at least two isoenzymes (DD2 and DD4) of 3 alpha
      hydroxysteroid/dihydrodiol dehydrogenase. The NADP(H)-linked oxidoreductase
      activities of DD4 were activated more than 4-fold by sulphobromophthalein at
      concentrations above 20 microM and under physiological pH conditions.
      Sulphobromophthalein did not stimulate the activities of DD2 and human liver
      aldehyde reductase, which are functionally and/or structurally related to DD4. No
      stimulatory effect on the activity of DD4 was observed with other organic anions
      such as Indocyanine Green, haematin and Rose Bengal. The binding of
      sulphobromophthalein to DD4 was instantaneous and reversible, and was detected by
      fluorescence and ultrafiltration assays. The activation by sulphobromophthalein
      decreased the activation energy in the dehydrogenation reaction for the enzyme,
      and increased both kcat, and Km values for the coenzymes and substrates. Kinetic
      analyses with respect to concentrations of NADP+ and (S)-(+)-indan-1-ol indicated
      that sulphobromophthalein was a non-essential activator of mixed type showing a
      dissociation constant of 2.6 microM. Thus, the human 3 alpha-hydroxysteroid
      dehydrogenase isoenzyme has a binding site specific to sulphobromophthalein, and
      the hepatic metabolism mediated by this isoenzyme may be influenced when this
      drug is administered.

PMID- 8546682
TI  - Purification and initial characterization of proline 4-hydroxylase from
      Streptomyces griseoviridus P8648: a 2-oxoacid, ferrous-dependent dioxygenase
      involved in etamycin biosynthesis.
AB  - Proline 4-hydroxylase is a 2-oxoacid, ferrous-ion-dependent dioxygenase involved
      in the biosynthesis of the secondary metabolite etamycin. The purification, in
      low yield, of proline 4-hydroxylase from Streptomyces griseoviridus P8648 to
      near, apparent homogeneity and its initial characterization are reported. In most
      respects proline 4-hydroxylase is a typical member of the 2-oxoacid-dependent
      dioxygenase family. It is monomeric (M(r) approx. 38,000) (by gel filtration on
      Superdex-G75) and has typically strict requirements for ferrous ion and 2
      oxoglutarate. The enzyme was inhibited by aromatic analogues of 2-oxoglutarate. L
      Proline-uncoupled turnover of 2-oxoglutarate to succinate and CO2 was observed.
      The addition of L-ascorbate did not stimulate L-proline-coupled turnover of 2
      oxoglutarate, but did stimulate L-proline-uncoupled turnover. L-Ascorbate caused
      a time-dependent inhibition of L-proline hydroxylation. The enzyme was completely
      inactivated by preincubation with diethyl pyrocarbonate under histidine-modifying
      conditions. This inactivation could be partially prevented by the inclusion of L
      proline and 2-oxoglutarate in the preincubation mixture, suggesting the presence
      of histidine residue(s) at the active site.

PMID- 8546679
TI  - Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory
      disease and progression to cancer.

PMID- 8546683
TI  - Characterization of a membrane protease from rat submaxillary-gland mitochondria
      that possess thrombin-like activity.
AB  - A membrane protease possessing thrombin-like activity was purified to homogeneity
      from mitochondria of rat submaxillary gland. The molecular mass of the enzyme was
      determined to be 45 kDa by SDS/PAGE under reducing conditions and by gel
      filtration on a Sephadex G-100 column. The enzyme is a glycoprotein and has an
      isoelectric point of 3.25. Maximum activity was observed at pH 10.5. Inhibition
      by di-isopropyl fluorophosphate, benzamidine, aprotinin and antipain suggested
      the enzyme to be a serine protease. Other inhibitors such as EDTA, soya-bean
      trypsin inhibitor, lima-bean trypsin inhibitor, TosLysCH2Cl and chymostatin did
      not alter the activity. The enzyme showed affinity towards different synthetic
      substrates (p-nitroanilide derivatives) containing arginine at the P1 position.
      Kinetic studies revealed that Kcat./Km was highest with the substrate N-Bz-Phe
      Val-Arg-p-nitroanilide. The enzyme exhibits significant plasma-coagulating
      activity. The coagulation initiated by the enzyme was not altered by concanavalin
      A, indicating that the carbohydrate moiety of the enzyme is not essential for
      this reaction. Further, this enzyme can catalyse the formation of fibrin clots
      from purified fibrinogen, which describes its thrombin-like activity. However, an
      antibody raised against the purified enzyme inhibited the plasma-clotting as well
      as fibrinogen-clotting activity of the enzyme. Fibrinogen coagulation by the
      enzyme was blocked in the presence of aprotinin, a protease inhibitor. Release of
      fibrinopeptides A and B from bovine fibrinogen by the enzyme has been shown by
      HPLC analysis. Our studies reveal that the enzyme reported here differs from
      trypsin, chymotrypsin and other mitochondrial proteases reported so far.

PMID- 8546684
TI  - The role of cell adhesion in retinoic acid-induced modulation of chondrocyte
      phenotype.
AB  - Retinoic acid (RA) treatment of a suspension of quail chondrocytes inhibits the
      expression of cartilage collagens and induces cell adhesion along with
      fibronectin expression. We asked whether the RA-induced modulation of the
      chondrocyte phenotype was dependent on cell adhesion. Prevention of cell adhesion
      blocks cell growth and many of the effects associated with RA, such as collagen
      II inhibition, collagen I activation and fibronectin induction. The activity of
      the bone/tendon promoter of the alpha 2(I) collagen gene was determined by
      measuring the transient expression of COL1A2-CAT, a chimaeric gene bearing 3500
      bp from upstream of the transcription start site of the human alpha 2(I) gene
      fused to the chloramphenicol acetyltransferase (CAT) gene. This promoter is
      activated only in permissive conditions for cell adhesion. The attachment
      activities of chondrocytes on protein substrates was studied by an in vitro cell
      adhesion assay. Untreated cells or cells maintained in suspension while
      undergoing RA treatment do not attach when replated on protein substrates.
      Chondrocytes treated with RA in permissive conditions for cell adhesion rapidly
      attach and spread instead on collagen-coated wells. Altogether the results
      suggest that cell adhesion plays a major role in RA-induced modulation of the
      chondrocyte phenotype.

PMID- 8546685
TI  - Oxygen and pH regulation of protein synthesis in mitochondria from Artemia
      franciscana embryos.
AB  - To identify factors responsible for the down-regulation of mitochondrial
      biosynthetic processes during anoxia in encysted Artemia franciscana embryos, the
      effects of oxygen limitation and pH on protein synthesis were investigated in
      isolated mitochondria. At the optimal pH of 7.5, exposure of mitochondria to
      anoxia decreases the protein synthesis rate by 79%. Rates were suppressed by a
      further 10% at pH 6.8, the intracellular pH (pHi) measured under anoxia in vivo.
      Matrix pH, measured under identical conditions, was 8.43 +/- 0.01 at an extra
      mitochondrial pH of 7.9 (mean +/- S.E.M., n = 3), 8.05 +/- 0.01 at pH 7.5, and
      7.10 +/- 0.01 at pH 6.8. The matrix pH did not vary (P > or = 0.20) as a function
      of oxygen availability during the 1 h assays. Intramitochondrial purine
      nucleotides varied little as a function of pH. In contrast, after 1 h of protein
      synthesis under anoxia, ATP levels decreased by up to 40%, whereas AMP, ADP and
      GDP concentrations increased, and GTP and GMP concentrations remained relatively
      constant. The addition of 1 mM ATP at the onset of anoxia maintained the ATP/ADP
      ratio at the aerobic value, but did not stabilized the GTP/GDP ratio or rescue
      rates of protein synthesis. Thus, at present, we cannot eliminate the possibility
      that the decrease in the GTP/GDP ratio during anoxia may contribute to the
      suppression of protein synthesis. The effect of anoxia was reversible; the rate
      of protein synthesis upon reoxygenation after a 30 min bout of anoxia was
      comparable (P = 0.14) with the pre-anoxic rate (193 +/- 17 and 174 +/- 6 pmol of
      leucine per mg of protein respectively, mean +/- S.E.M., n = 3). The array of
      mitochondrial translation products did not differ qualitatively as a function of
      either oxygen availability or pH. Finally, similar pH profiles for protein
      synthesis were obtained with either [3H]leucine or [3H]histidine (known to use
      different transporters). Consequently, it is improbable that the pH-sensitivity
      of protein synthesis can be explained by a specific protein effect on the import
      of the radiolabelled amino acid used. In summary, both oxygen limitation and
      acidic pH suppress rates of mitochondrial protein synthesis and are likely to
      contribute to the arrest of mitochondrial anabolic processes during anoxia
      induced quiescence in A. franciscana embryos.

PMID- 8546686
TI  - Sphingomyelinase stimulates 2-deoxyglucose uptake by skeletal muscle.
AB  - The effects of sphingomyelinase, phosphorylcholine, N-acetylsphingosine (C2
      ceramide), N-hexanoylsphingosine (C6-ceramide) and sphingosine on basal and
      insulin-stimulated cellular accumulation of 2-deoxy-D-glucose in rat soleus
      muscles were investigated. Preincubation of muscles with sphingomyelinase (100 or
      200 m-units/ml) for 1 or 2 h augmented basal 2-deoxyglucose uptake by 29-91%, and
      that at 0.1 and 1.0 m-unit of insulin/ml 32-82% and 19-25% respectively compared
      with control muscles studied at the same insulin concentrations. The
      sphingomyelinase-induced increase in basal and insulin-stimulated 2-deoxyglucose
      uptake was inhibited by 91% by 70 microM cytochalasin B, suggesting that it
      involves glucose transporters. Sphingomyelinase had no effect on the cellular
      accumulation of L-glucose, which is not transported by glucose transporters. The
      sphingomyelinase-induced increase in 2-deoxyglucose uptake could not be
      reproduced by preincubating the muscles with 50 microM phosphorylcholine, 50
      microM C2-ceramide or 50 microM C6-ceramide. Preincubation of muscles with 50
      microM sphingosine augmented basal 2-deoxyglucose transport by 32%, but reduced
      the response to 0.1 and 1.0 m-unit of insulin/ml by 17 and 27% respectively. The
      stimulatory effect of sphingomyelinase on basal and insulin-induced 2
      deoxyglucose uptake was not influenced by either removal of Ca2+ from the
      incubation medium or dantrolene, an inhibitor of Ca2+ release from the
      sarcoplasmic reticulum. This demonstrates that Ca2+ does not mediate the action
      of sphingomyelinase on 2-deoxyglucose uptake. Sphingomyelinase also had no effect
      on basal and insulin-stimulated activities of insulin receptor tyrosine kinase
      and phosphatidylinositol 3-kinase. In addition, 1 and 5 microM wortmannin, an
      inhibitor of phosphatidylinositol 3-kinase, failed to inhibit the
      sphingomyelinase-induced increase in 2-deoxyglucose uptake. These results suggest
      that sphingomyelinase does not increase 2-deoxyglucose uptake by stimulating the
      insulin receptor or the initial steps of the insulin-transduction pathway. The
      data suggest the possibility that sphingomyelinase increases basal and insulin
      stimulated 2-deoxyglucose uptake in skeletal muscle as the result of an unknown
      post-receptor effect.

PMID- 8546687
TI  - Purification and characterization of prostaglandin-H E-isomerase, a sigma-class
      glutathione S-transferase, from Ascaridia galli.
AB  - Comparison of partial primary sequences of sigma-class glutathione S-transferases
      (GSH) of parasitic helminths and a GSH-dependent prostaglandin (PG)-H D-isomerase
      of rat immune accessory cells suggested that some of the helminth enzymes may
      also be involved in PG biosynthesis [Meyer and Thomas (1995) Biochem. J. 311, 739
      742]. A soluble GSH transferase of the parasitic nematode Ascaridia galli has now
      been purified which shows high activity and specificity in the GSH-dependent
      isomerization of PGH to PGE, comparable to that of the rat spleen enzyme in its
      isomerization of PGH to PGD, and similarly stimulates the activity of
      prostaglandin H synthase. The enzyme subunit is structurally related to the rat
      spleen enzyme and sigma-class GSH transferases of helminths according to the
      partial primary sequence. The data support the hypothesis that some sigma-class
      GSH transferases of helminth parasites are involved in PG biosynthesis which, in
      the case of PGE, is likely to be associated with the subversion or suppression of
      host immunity. A PG-H E-isomerase of comparable specificity and activity has not
      previously been isolated.

PMID- 8546688
TI  - Glycine decarboxylase and pyruvate dehydrogenase complexes share the same
      dihydrolipoamide dehydrogenase in pea leaf mitochondria: evidence from mass
      spectrometry and primary-structure analysis.
AB  - In order to compare the dihydrolipoamide dehydrogenase associated with the
      pyruvate dehydrogenase complex (E3) with that associated with the glycine
      decarboxylase complex (L-protein), we report for the first time the purification
      and characterization of the E3 component from pea leaf mitochondria. The first 30
      amino acids of the N-terminal sequence of the mature E3 protein are identical
      with those of the mature L-protein of the glycine decarboxylase complex.
      Electrospray ionization-mass spectrometric analysis of E3 and the L-protein gave
      exactly the same molecular mass of 49,753 +/- 5 Da. We have also confirmed the
      primary structure of the L-protein, in particular the C-terminal sequence,
      deduced from the cDNA published by Bourguignon, Macherel, Neuburger and Douce
      [(1992) Eur. J. Biochem. 204, 865-873]. Western-blot analysis shows that specific
      polyclonal antibodies raised against the L-protein recognize specifically both E3
      and L-protein but not the porcine dihydrolipoamide dehydrogenase. We conclude
      that, in pea leaf mitochondria, the pyruvate dehydrogenase and glycine
      decarboxylase complexes share the same dihydrolipoamide dehydrogenase. We have
      also confirmed by MS analysis that the FAD is not covalently bound to the enzyme.

PMID- 8546689
TI  - Substitution of glycine for arginine-213 in extracellular-superoxide dismutase
      impairs affinity for heparin and endothelial cell surface.
AB  - Extracellular-superoxide dismutase (EC-SOD) levels in sera divide into two
      discontinuous groups: a low-level group below 400 ng/ml and a high-level group
      above 400 ng/ml [Adachi, Nakamura, Yamada, Futenma, Kato and Hirano (1994) Clin.
      Chim. Acta 229, 123-131]. Molecular genetic studies have shown that the donors in
      the high-level group have a single base substitution generating the exchange of
      glycine for arginine-213 (R213G) in the heparin-binding domain of EC-SOD
      [Sandstrom, Nilsson, Karlsson and Marklund (1994) J. Biol. Chem. 269, 19163
      19166; Yamada, Yamada, Adachi, Goto, Ogasawara, Futenma, Kitano, Hirano and Kato
      (1995) Jpn. J. Hum. Genet. 40, 177-184]. The serum EC-SOD level in homozygote
      subjects was significantly higher than that in heterozygotes and in normal
      subjects. Serum EC-SOD from heterozygotes and homozygotes had equally decreased
      affinity for heparin, as judged by heparin-HPLC, as compared with that from
      normal donors. This result suggests that the serum EC-SOD in heterozygotes was
      mainly composed of the mutant form which has reduced heparin affinity. On the
      other hand, fibroblast cells derived from heterozygote subjects generated mRNA of
      both normal and mutant EC-SOD (m-EC-SOD), and expressed the corresponding
      proteins. EC-SOD is a tetrameric enzyme, and in heterozygote donors would be
      heterogeneous with regard to the constitution of normal and mutant subunits. The
      enzyme form consisting of only mutant subunits, the form with the weakest heparin
      affinity, can be preferentially driven out to the plasma phase, because EC-SOD in
      the vasculature exists in equilibrium between plasma and the endothelial cell
      surface. The binding of m-EC-SOD to bovine aortic endothelial cells was about 50
      fold less than that of normal EC-SOD. This result suggests that the binding of m
      EC-SOD to vascular endothelial cells is much decreased in vivo, which causes a
      high level of serum EC-SOD.

PMID- 8546690
TI  - Electrospray mass spectrometric evidence for the occurrence of two major variants
      in native pig pepsin A.
AB  - Native pig pepsin was analysed by negative ion electrospray mass spectrometry in
      order to rationalize anomalies between the published sequences. Outstanding
      variations in otherwise identical sequences indicate that amino acid residue 242
      is either Asp or Tyr, and in some determinations an additional Ile is inserted at
      position 230. Mass spectrometric evidence is consistent with the presence, in the
      native enzyme, of two variants in comparable abundance, with either Asp or Tyr at
      residue 242. There is no evidence for the additional Ile at position 230.

PMID- 8546691
TI  - PEST motifs are not required for rapid calpain-mediated proteolysis of c-fos
      protein.
AB  - Cytoplasmic degradation of c-fos protein is extremely rapid. Under certain
      conditions, it is a multi-step process initiated by calcium-dependent and ATP
      independent proteases called calpains. PEST motifs are peptide regions rich in
      proline, glutamic acid/aspartic acid and serine/threonine residues, commonly
      assumed to constitute built-in signals for rapid recognition by intracellular
      proteases and particularly by calpains. Using a cell-free degradation assay and
      site-directed mutagenesis, we report here that the three PEST motifs of c-fos are
      not required for rapid cleavage by calpains. Testing the susceptibility of PEST
      motif-bearing and non-bearing transcription factors including GATA1, GATA3, Myo
      D, c-erbA, Tal-1 and Sry, demonstrates that PEST sequences are neither necessary
      nor sufficient for specifying degradation of other proteins by calpains. This
      conclusion is strengthened by the observation that certain proteins, reportedly
      known to be cleavable by calpains, are devoid of PEST motifs.

PMID- 8546692
TI  - Isolation and characterization of a Chinese hamster ovary (CHO) mutant defective
      in the second step of glycosylphosphatidylinositol biosynthesis.
AB  - Mutant cell lines defective in the biosynthesis of glycosylphosphatidylinositol
      (GPI) described to date were isolated by selecting cells which no longer
      expressed one or more endogenous GPI-anchored proteins on their surface. In this
      study, a new mutant in this pathway was isolated from ethylmethane-sulphonate
      mutagenized Chinese hamster ovary cells stably transfected with human placental
      alkaline phosphatase (PLAP) as a marker of GPI-anchored proteins. A three-step
      protocol was employed. In the first step, cells with decreased surface expression
      of PLAP were selected by four rounds of complement-mediated lysis with an anti
      (alkaline phosphatase) antibody. The surviving cells were cloned by limiting
      dilution and those with low levels of total alkaline phosphatase activity were
      selected in the second step. Finally, the ability of each clone to synthesize the
      first three intermediates in GPI biosynthesis in vitro was assessed to determine
      which cells with low alkaline phosphatase activity harboured a defect in one of
      these reactions. Of 230 potential mutants, one was defective in the second step
      of GPI biosynthesis. Microsomes from this mutant, designated G9PLAP.85, were
      completely unable to deacetylate either endogenous GlcNAc-phosphatidylinositol
      (PI) synthesized from UDP[6-3H]GlcNAc or exogenous GlcNAc-PI added directly to
      the membranes. Complementation analysis with the Thy-1-deficient murine lymphoma
      cells demonstrated that G9PLAP.85 has a molecular defect distinct from these
      previously described mutants. Therefore, these results suggest that mutants in
      GPI biosynthesis could be selected from almost any cell line expressing a GPI
      anchored marker protein.

PMID- 8546693
TI  - Specific co-ordinated regulation of PC3 and PC2 gene expression with that of
      preproinsulin in insulin-producing beta TC3 cells.
AB  - Short-term (less than 2 h) glucose stimulation of isolated pancreatic islets
      specifically increases the biosynthesis of proinsulin and its converting enzymes
      PC2 and PC3 at the translation level. To determine whether gene expression of PC2
      and PC3 was also regulated by longer-term (more than 6 h) glucose stimulation
      along with that of preproinsulin, studies were performed with the beta TC3
      insulin-producing cell line. By Northern blot analysis, glucose maintained PC2
      and PC3 mRNA levels in parallel with those of preproinsulin. After 48 h, mRNA
      levels of preproinsulin, PC2 and PC3 were, respectively, 2.9 (P < 0.05), 3.0 (P <
      0.005) and 5.3 (P < 0.001) times greater in the presence of glucose than in beta
      TC3 cells cultured in the absence of glucose. Glucose-regulated PC2 and PC3 gene
      expression, like that of preproinsulin, was maximal at glucose concentrations
      above 5.5 mM. Studies of mRNA stability showed that the half-lives of PC2 (9 h)
      and PC3 (5 h) mRNA were much shorter than that of preproinsulin mRNA (over 24 h),
      but little effect of glucose on stability of these mRNAs was observed. Nuclear
      run-off analysis indicated that transcription of preproinsulin, PC2 and PC3 was
      modestly induced after 1 h exposure to 16.7 mM glucose. Therefore preproinsulin,
      PC2 and PC3 mRNA levels in beta TC3 cells were most probably maintained at the
      level of gene transcription. In contrast, elevation of cyclic AMP by forskolin
      had no effect on mRNA levels or gene transcription of preproinsulin, PC2 and PC3,
      despite a cyclic-AMP-induced phosphorylation of the cyclic AMP response element
      binding protein that correlated with a marked increase in cJun and cFos gene
      transcription in the same beta-cells. These results suggest that preproinsulin,
      PC2 and PC3 gene transcription can be specifically glucose-regulated in a
      mechanism that is unlikely to involve a key role for cyclic AMP. The co-ordinate
      increase in PC2 and PC3 mRNA levels with that of preproinsulin mRNA in response
      to chronic glucose represents a long-term means of catering for an increased
      demand on proinsulin conversion.

PMID- 8546694
TI  - A synthetic oestrogen antagonist, tamoxifen, inhibits oestrogen-induced
      transcriptional, but not post-transcriptional, regulation of gene expression.
AB  - Oestrogen (E2) regulates the expression of its target genes at transcriptional
      and post-transcriptional levels. To clarify the mechanism of E2-induced post
      transcriptional regulation, with attention to the involvement of the oestrogen
      receptor (ER), we studied the effect of tamoxifen (TAM), a synthetic E2
      antagonist that inhibits ER-mediated transcription, on E2-induced transcriptional
      and post-transcriptional regulation of the chicken ovalbumin (OVA) gene in chick
      oviducts. Run-on analysis with oviduct nuclei isolated from E2-treated chicks
      showed that TAM treatment completely blocked E2-induced transcription of the OVA
      gene within 24 h without affecting ER gene expression. Likewise, the rate of
      transcription fell to below the limit of detection after E2 withdrawal from the
      chicks. Reflecting the transcription rate, OVA mRNA accumulated linearly in E2
      treated chicks, and E2 withdrawal caused a rapid loss of OVA mRNA. However, in
      the chicks treated with TAM and E2, OVA mRNA was degraded slowly over 48 h with a
      half-life of 24 h, suggesting that TAM does not inhibit E2-induced mRNA
      stabilization. Moreover, E2-induced mRNA stabilization was observed even when
      transcription of the OVA gene was blocked by a transcription inhibitor. Western
      blot analysis showed that the remaining OVA mRNA was translatable. Thus the
      present study indicates that E2 regulates expression of the OVA gene via distinct
      pathways at transcriptional and post-transcriptional levels.

PMID- 8546695
TI  - The mechanism of human plasma phospholipid transfer protein-induced enlargement
      of high-density lipoprotein particles: evidence for particle fusion.
AB  - 1. Phospholipid transfer protein (PLTP) mediates conversion of high-density
      lipoprotein (HDL3) to large particles, with concomitant release of apolipoprotein
      A-I (apoA-I). To study the mechanisms involved in this conversion, reconstituted
      HDL (rHDL) particles containing either fluorescent pyrenylacyl cholesterol ester
      (PyrCE) in their core (PyrCE-rHDL) or pyrenylacyl phosphatidylcholine (PysPC) in
      their surface lipid layer (PyrPC-rHDL) were prepared. Upon incubation with PLTP
      they behaved as native HDL3, in that their size increased considerably. 2. When
      PyrPC-rHDL was incubated with HDL3 in the presence of PLTP, a rapid decline of
      the pyrene excimer/monomer fluorescence ratio (E/M) occurred, demonstrating that
      PLTP induced mixing of the surface lipids of PyrPC-rHDL and HDL3. As this mixing
      was almost complete before any significant increase in HDL particle size was
      observed, it represents PLTP-mediated phospholipid transfer or exchange that is
      not directly coupled to the formation of large HDL particles. 3. When core
      labelled PyrCE-rHDL was incubated in the presence of PLTP, a much slower, time
      dependent decrease of E/M was observed, demonstrating that PLTP also promotes
      mixing of the core lipids. The rate and extent of mixing of core lipids
      correlated with the amount of PLTP added and with the increase in particle size.
      The enlarged particles formed could be visualized as discrete, non-aggregated
      particles by electron microscopy. Concomitantly with the appearance of enlarged
      particles, lipid-poor apoA-I molecules were released. These data, together with
      the fact that PLTP has been shown not to mediate transfer of cholesterol esters,
      strongly suggest that particle fusion rather than (net) lipid transfer or
      particle aggregation is responsible for the enlargement of HDL particles observed
      upon incubation with PLTP.4.ApoA-I rHDL, but not apoA-II rHDL, were converted
      into large particles, suggesting that the presence of apoA-I is required for PLTP
      mediated HDL fusion. A model for PLTP-mediated enlargement of HDL particles is
      presented.

PMID- 8546696
TI  - Characterization of an insulin from the three-toed amphiuma (Amphibia: Urodela)
      with an N-terminally extended A-chain and high receptor-binding affinity.
AB  - Insulin was isolated from an extract of the pancreas of a urodele, the three-toed
      amphiuma (Amphiuma tridactylum), and its primary structure established as Ala-Arg
      Gly-Ile-Val-Glu-Gln-Cys-Cys-His10-Asn-Thr-Cys- Ser-Leu-Asn-Gln-Leu-Glu-Asn20-Tyr
      Cys-Asn for the A-chain and Ile-Thr-Asn-Gln-Tyr-Leu-Cys-Gly-Ser-His10-Leu-Val-Glu
      Ala- Leu-Tyr-Leu-Val-Cys-Gly20-Asp-Arg-Gly-Phe-Phe-Tyr-Ser-Pro-Lys for the B
      chain. The N-terminus of the A-chain is extended by two amino acids (Ala-Arg)
      relative to all other known insulins suggesting an anomalous pathway of post
      translational processing in the region of the C-peptide/A-chain junction of
      proinsulin. In common with chicken and Xenopus insulins, which contain a HisA8,
      amphiuma insulin was more potent (approx. 5-fold) than porcine insulin in
      inhibiting the binding of [125I-TyrA14]insulin to the soluble human insulin
      receptor from transfected 293EBNA cells (an adenovirus-transformed human kidney
      cell line). This result is consistent with previous data showing that insulin
      analogues extended at GlyA1 by uncharged groups have reduced binding affinity
      whereas high affinity is preserved in analogues extended by basic amino acid
      residues.

PMID- 8546697
TI  - Recognition of lactoferrin and aminopeptidase M-modified lactoferrin by the
      liver: involvement of proteoglycans and the remnant receptor.
AB  - 1. Lactoferrin and aminopeptidase M-modified lactoferrin (APM-lactoferrin; which
      lacks its 14 N-terminal amino acids) inhibit the liver uptake of lipoprotein
      remnant. In the present study, the role of proteoglycans in the initial
      interaction of beta-migrating very-low-density lipoprotein (beta-VLDL), native
      and APM-lactoferrin with isolated rat parenchymal liver cells was investigated.
      Treatment of the cells with chondroitinase lowered the Kd of lactoferrin binding
      (from 10 to 2.4 microM), and the number of sites/cell (from 20 x 10(6) to 7 x
      10(6)), while heparinase treatment did not affect the binding. The binding
      characteristics of APM-lactoferrin and beta-VLDL were not altered by treatment of
      the cells with chondroitinase or heparinase. It is concluded that proteoglycans
      are not involved in the initial binding of APM-lactoferrin and beta-VLDL to
      parenchymal cells, while chondroitin sulphate proteoglycans are mainly
      responsible for the massive, low-affinity binding of native lactoferrin..2. The
      binding of lactoferrin, APM-lactoferrin and beta-VLDL to parenchymal liver cells
      was not influenced by the glutathione S-transferase-receptor-associated protein
      (GST-RAP) (97.2% +/- 4.0%, 95.5 +/- 3.7% and 98.5% of the control binding), while
      the binding of alpha 2-macroglobulin was fully blocked at 10 micrograms/ml GST
      RAP (1.8 +/- 0.5% of the control binding). Since GST-RAP blocks the binding of
      all the known ligands to the low-density lipoprotein (LDL)-receptor-related
      protein (LRP), it is concluded that LRP is not the initial primary recognition
      site for lactoferrin, APM-lactoferrin and beta-VLDL on parenchymal liver cells.
      3. We showed earlier that.APM-lactoferrin, as compared with lactoferrin, is a
      more effective inhibitor of the liver uptake of lipoprotein remnants (49.4 +/-
      4.0% versus 80.8 +/- 4.8% of the control at 500 micrograms/ml respectively). We
      found in the present study that beta-VLDL is able to inhibit the binding of APM
      lactoferrin to parenchymal liver cells significantly (74.9 +/- 3.3% of the
      control; P < 0.002), while the lactoferrin binding was unaffected. It is
      concluded that a still unidentified specific recognition site (the putative
      remnant receptor) is responsible for the initial binding of remnants to
      parenchymal cells and it is suggested that the partial cross-competition between
      APM-lactoferrin and beta-VLDL may be of further help in the elucidation of the
      molecular nature of this recognition site.

PMID- 8546698
TI  - Analysis of the role of N-glycosylation in cell-surface expression and binding
      properties of angiotensin II type-2 receptor of rat pheochromocytoma cells.
AB  - We previously demonstrated that the AT2 receptor is a glycoprotein containing N
      linked oligosaccharide side chains and that the marked disparity between the
      sizes of AT2 receptors from different tissues was related to different degrees of
      N-glycosylation. In the present study, we used an inhibitor of N-glycosylation,
      tunicamycin, as well as an endoglycosidase, glycopeptidase-F, to examine the
      contribution of carbohydrate moieties to the ligand-binding properties, cell
      surface expression and apparent molecular mass of AT2 receptors of rat
      pheochromocytoma cells (PC-12 cells). Photoaffinity labelling of cell-surface AT2
      receptors revealed that PC-12 cells grown in the presence of tunicamycin
      expressed, in addition to the previously described 140 kDa receptor, lower
      molecular-mass receptors of 63 kDa, 47 kDa and 32 kDa. Lectin affinity
      chromatography revealed that the 63 kDa and the 47 kDa receptors are partially
      glycosylated and that the 32 kDa receptor is completely deglycosylated.
      Competitive binding experiments were carried out on tunicamycin-treated cells
      that expressed predominantly the 63 kDa or the 47 kDa receptors. Both receptor
      forms exhibited a high affinity for angiotensin II, although a slight decrease
      (of about 2-fold) was consistently observed on tunicamycin-treated cells as
      compared with control cells. Endoglycosidase digestion of AT2 receptors of PC-12
      cells also yielded smaller receptor forms of 47 kDa and 32 kDa. Similarly,
      angiotensin II showed a high but slightly decreased binding affinity (of about 2
      fold) for deglycosylated membranes as compared with control membranes. In
      conclusion, the stepwise action of tunicamycin suggests the presence of at least
      three N-linked oligosaccharide side chains on the AT2 receptor of PC-12 cells.
      These oligosaccharide side chains have a minor contribution to the affinity of
      the receptor. Interestingly, glycosylation is not an essential requirement for
      the expression of AT2 receptor at the surface of PC-12 cells.

PMID- 8546699
TI  - Transglutaminase induced by epidermal growth factor negatively regulates the
      growth signal in primary cultured hepatocytes.
AB  - Transglutaminase (TGase) activity increased 2.5-fold at 6 h after treatment of
      rat hepatocytes with 17 nM epidermal growth factor (EGF). In the same manner,
      putrescine incorporation into the proteins of cells occurred in EGF-treated
      cells, but not in those pretreated with monodansylcadaverine (MDC), a TGase
      inhibitor, even in the presence of EGF. These results suggest that EGF-induced
      TGase was active and catalysed some cross-linkage reaction. Cycloheximide
      completely blocked the increase in TGase activity induced by EGF, suggesting that
      EGF stimulated de novo synthesis of TGase within 6 h. Furthermore, Northern
      blotting analysis indicated that EGF increased the expression of TGase mRNA.
      Pretreatment of cells with MDC additionally increased EGF-induced DNA-synthesis
      and the ratio of cells in S-phase. TGase antisense oligonucleotide inhibited de
      novo synthesis of TGase, resulting in increases in the ratios of S- and G2/M
      phase cells in the presence of EGF. This effect was the result of inhibition of
      EGF-induced down-regulation of high-affinity receptor expression. These results
      suggest that the EGF-induced increase in TGase activity is a negative regulator
      of a growth signal in rat hepatocytes.

PMID- 8546700
TI  - Brain accumulation of myo-inositol in the trisomy 16 mouse, an animal model of
      Down's syndrome.
AB  - myo-Inositol and several other polyols were measured in the tissues of the
      trisomy 16 mouse (animal model of Down's Syndrome; human trisomy 21) and diploid
      controls. myo-Inositol was found to be selectively elevated in the brain of the
      trisomy 16 mouse. However, peripheral tissues showed no elevation. These results
      are consistent with the cerebrospinal fluid and plasma data reported previously
      on myo-inositol in Down's Syndrome subjects.

PMID- 8546701
TI  - Inducible UDP-glucose dehydrogenase from French bean (Phaseolus vulgaris L.)
      locates to vascular tissue and has alcohol dehydrogenase activity.
AB  - UDP-glucose dehydrogenase is responsible for channelling UDP-glucose into the
      pool of UDP-sugars utilized in the synthesis of wall matrix polysaccharides and
      glycoproteins. It has been purified to homogeneity from suspension-cultured cells
      of French bean by a combination of hydrophobic-interaction chromatography, gel
      filtration and dye-ligand chromatography. The enzyme had a subunit of Mr 40,000.
      Km values were measured for UDP-glucose as 5.5 +/- 1.4 mM and for NAD+ as 20 +/-
      3 microM. It was subject to inhibition by UDP-xylose. UDP-glucose dehydrogenase
      activity co-purified with alcohol dehydrogenase activity from suspension-cultured
      cells, elicitor-treated cells and elongating hypocotyls, even when many
      additional chromatographic steps were employed subsequently. The protein from
      each source was resolved into virtually identical patterns of isoforms on two
      dimensional isoelectric focusing/PAGE. However, a combination of peptide mapping
      and sequence analysis, gel analysis using activity staining and kinetic analysis
      suggests that both activities are a function of the same protein. An antibody was
      raised and used to immunolocalize UDP-glucose dehydrogenase to developing xylem
      and phloem of French bean hypocotyl. Together with data published previously,
      these results are consistent with an important role in the regulation of carbon
      flux into wall matrix polysaccharides.

PMID- 8546702
TI  - A new inositol 1,4,5-trisphosphate binding protein similar to phospholipase C
      delta 1.
AB  - We have reported that two inositol 1,4,5-trisphosphate binding proteins, with
      molecular masses of 85 and 130 kDa, were purified from rat brain; the former
      protein was found to be the delta 1-isoenzyme of phospholipase C (PLC-delta 1)
      and the latter was an unidentified novel protein [Kanematsu, Takeya, Watanabe,
      Ozaki, Yoshida, Koga, Iwanaga and Hirata (1992) J. Biol. Chem. 267, 6518-6525].
      Here we describe the isolation of the full-length cDNA for the 130 kDa
      Ins(1,4,5)P3 binding protein, which encodes 1096 amino acids. The predicted
      sequence of the 130 kDa protein had 38.2% homology to that of PLC-delta 1. Three
      known domains of PLC-delta 1 (pleckstrin homology and putative catalytic X and Y
      domains) were located at residues 110-222, 377-544 and 585-804 with 35.2%, 48.2%
      and 45.8% homologies respectively. However, the protein showed no PLC activity to
      phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol. The 130 kDa
      protein expressed by transfection in COS-1 cells bound Ins(1,4,5)P3 in the same
      way as the molecule purified from brain. Thus the 130 kDa protein is a novel
      Ins(1,4,5)P3 binding protein homologous to PLC-delta 1, but with no catalytic
      activity. The functional significance of the 130 kDa protein is discussed.

PMID- 8546703
TI  - The specificity of mitochondrial complex I for ubiquinones.
AB  - We report the first detailed study on the ubiquinone (coenzyme Q; abbreviated to
      Q) analogue specificity of mitochondrial complex I, NADH:Q reductase, in intact
      submitochondrial particles. The enzymic function of complex I has been
      investigated using a series of analogues of Q as electron acceptor substrates for
      both electron transport activity and the associated generation of membrane
      potential. Q analogues with a saturated substituent of one to three carbons at
      position 6 of the 2,3-dimethoxy-5-methyl-1,4-benzoquinone ring have the fastest
      rates of electron transport activity, and analogues with a substituent of seven
      to nine carbon atoms have the highest values of association constant derived from
      NADH:Q reductase activity. The rate of NADH:Q reductase activity is potently but
      incompletely inhibited by rotenone, and the residual rotenone-insensitive rate is
      stimulated by Q analogues in different ways depending on the hydrophobicity of
      their substituent. Membrane potential measurements have been undertaken to
      evaluate the energetic efficiency of complex I with various Q analogues. Only
      hydrophobic analogues such as nonyl-Q or undecyl-Q show an efficiency of membrane
      potential generation equivalent to that of endogenous Q. The less hydrophobic
      analogues as well as the isoprenoid analogue Q-2 are more efficient as substrates
      for the redox activity of complex I than for membrane potential generation. Thus
      the hydrophilic Q analogues act also as electron sinks and interact incompletely
      with the physiological Q site in complex I that pumps protons and generates
      membrane potential.

PMID- 8546704
TI  - Biosynthesis of vitamin B12: the preparative multi-enzyme synthesis of precorrin
      3A and 20-methylsirohydrochlorin (a 2,7,20-trimethylisobacteriochlorin).
AB  - The Bacillus subtilis genes hemB, hemC and hemD, encoding respectively the
      enzymes porphobilinogen synthase, hydroxymethylbilane synthase and
      uroporphyrinogen III synthase, have been expressed in Escherichia coli using a
      single plasmid construct. An enzyme preparation from this source converts 5
      aminolaevulinic acid (ALA) preparatively and in high yield into uroporphyrinogen
      III. The Pseudomonas denitrificans genes cobA and cobI, encoding respectively the
      enzymes S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase (SUMT) and
      S-adenosyl-L-methionine:precorrin-2 methyltransferase (SP2MT), were also
      expressed in E. coli. When SUMT was combined with the coupled-enzyme system that
      produces uroporphyrinogen III, precorrin-2 was synthesized from ALA, and when
      SP2MT was also added the product from the coupling of five enzymes was precorrin
      3A. Both of these products are precursors of vitamin B12, and they can be used
      directly for biosynthetic experiments or isolated as their didehydro octamethyl
      esters in > 40% overall yield. The enzyme system which produces precorrin-3A is
      sufficiently stable to allow long incubations on a large scale, affording
      substantial quantities (15-20 mg) of product.

PMID- 8546705
TI  - Structural characterization of the latent complex between transforming growth
      factor beta 1 and beta 1-latency-associated peptide.
AB  - The formation of a non-covalent complex between mature transforming growth factor
      beta 1 (TGF-beta 1) and its pro region, the beta 1-latency-associated peptide
      (beta 1-LAP), is important in regulating the activity of this multipotent growth
      factor. We have overexpressed simian beta 1-LAP in Chinese hamster ovary (CHO)
      cells to produce a cell line which secretes beta 1-LAP into the culture medium at
      > 1 mg/l, thus enabling structural studies of complex formation between beta 1
      LAP and TGF-beta 1. The simian beta 1-LAP expressed in CHO cells reversed the
      growth inhibitory effect of exogenous TGF-beta 1 on Mv1Lu (mink lung epithelial)
      cells and was able to form a cross-linked complex with 125I-TGF-beta 1. Simian
      beta 1-LAP was purified to homogeneity by a combination of ammonium sulphate
      precipitation, gel filtration, dye ligand chromatography and anion-exchange
      chromatography, with a yield of 15%. The purified protein had an apparent
      molecular mass of 114 kDa as determined by SDS/PAGE, which is greater than that
      determined for the transient expression of simian beta 1-LAP in COS-1 and for the
      simian precursor of TGF-beta 1 (pro-TGF-beta 1) in CHO cells, this major
      difference being due to more extensive glycosylation of beta 1-LAP expressed by
      this CHO clone. Far-UV CD spectroscopy of simian beta 1-LAP indicates a mostly
      beta-sheet structure, with extensive structural rearrangements occurring upon
      formation of the latent complex between TGF-beta 1 and beta 1-LAP.

PMID- 8546706
TI  - A redox-based mechanism for induction of interleukin-1 production by nitric oxide
      in a human colonic epithelial cell line (HT29-Cl.16E).
AB  - We evaluated the effects of two NO donors, sodium nitroprusside (SNP) and 3
      morpholino-sydnonimine (SIN-1), characterized by alternative redox states, i.e.
      nitrosonium ion (NO+) and nitric oxide (NO.) respectively, on intracellular
      interleukin-1 (IL-1) production, by a human colonic epithelial cell line (HT29
      Cl.16E). SNP was able to induce intracellular IL-1 alpha production up to 10 h
      incubation, in a dose-dependent manner. Several experiments provide evidence that
      the NO+ redox form, and not the free radical NO., is implicated in the IL-1 alpha
      production: (i) SIN-1, devoid of any NO+ character, led to a very weak IL-1
      production as compared with SNP; (ii) the reductive action of a thiol such as
      cysteine on NO+ led to a dose-dependent increase in NO, concentration, measured
      as NO2-/NO3- accumulation, and to large decrease in IL-1 production. Dibutyryl
      cGMP had no effect on IL-1 production, this finding supporting the concept that a
      cGMP-independent pathway is involved in the intracellular signalling of NO+.
      Together these results point out that NO, depending on its redox form, is able to
      modulate IL-1 production in cultured colonic epithelial cells.

PMID- 8546707
TI  - Transcriptional activation of the chicken lysozyme gene by NF-kappa Bp65 (RelA)
      and c-Rel, but not by NF-kappa Bp50.
AB  - The lysozyme gene is expressed at a low level in myeloblasts and is progressively
      activated to constitutively high expression in mature macrophages. The binding
      activity of the newly defined NF-kappa B/Rel family of transcription factors
      increases during the terminal differentiation of macrophages. In this study, I
      show that NF-kappa B/Rel-like proteins bind to the nuclear factor kappa B (kappa
      B)-like sequence of the lysozyme promoter. These binding activities were induced
      by treatment of HD11 cells with lipopolysaccharide. Immunomobility shift assays
      show that c-Rel is possibly a factor in the complexes that bind to the kappa B
      like sequence lys kappa B. Binding activity to one of the protein complexes seems
      to be regulated by phosphorylation. In fact, overexpression of p65 and c-Rel
      stimulates expression of the chloramphenicol acetyltransferase gene controlled by
      the lysozyme promoter. Furthermore, co-transfection experiments reveal that the
      kappa B-like sequence within the lysozyme promoter mediates the transactivation
      by p65 and c-Rel. These results indicate that the p65 and c-Rel could be
      components of the protein complexes that bind to the kappa B-like sequence and
      this binding could contribute to the progressively activated expression of the
      lysozyme gene during the terminal differentiation of macrophages.

PMID- 8546708
TI  - Multiple mechanisms for the phosphorylation of C-terminal regulatory sites in
      rabbit muscle glycogen synthase expressed in COS cells.
AB  - Glycogen synthase can be inactivated by sequential phosphorylation at the C
      terminal residues Ser652 (site 4), Ser648 (site 3c), Ser644 (site 3b) and Ser640
      (site 3a) catalysed by glycogen synthase kinase-3. In vitro, glycogen synthase
      kinase-3 action requires that glycogen synthase has first been phosphorylated at
      Ser656 (site 5) by casein kinase II. Recently we demonstrated that inactivation
      is linked only to phosphorylation at site 3a and site 3b, and that, in COS cells,
      modification of these sites can occur by alternative mechanisms independent of
      any C-terminal phosphorylations [Skurat and Roach (1995) J. Biol. Chem. 270,
      12491-12497]. To address these mechanisms multiple Ser-->Ala mutations were
      introduced in glycogen synthase such that only site 3a or site 3b remained
      intact. Additional mutation of Arg637-->Gln eliminated phosphorylation of site
      3a, indicating that Arg637 may be important for recognition of site 3a by its
      corresponding protein kinase(s). Similarly, additional mutation of Pro645-->Ala
      eliminated phosphorylation of site 3b, indicating a possible involvement of
      'proline-directed' protein kinase(s). Mutation of Arg637 alone did not activate
      glycogen synthase as expected from the loss of phosphorylation at site 3a.
      Rather, mutation of both Arg637 and the Ser-->Ala substitution at site 3b was
      required for substantial activation. The results suggest that sites 3a and 3b can
      be phosphorylated independently of one another by distinct protein kinases.
      However, phosphorylation of site 3b can potentiate phosphorylation of site 3a, by
      an enzyme such as glycogen synthase kinase-3.

PMID- 8546709
TI  - Annexin II up-regulates cellular levels of p11 protein by a post-translational
      mechanisms.
AB  - Annexin II (p36) and p11, which belong to two different families of calcium
      binding proteins, are able to form a heterotetrameric protein complex
      (p36)2(p11)2 called calpactin I. As these proteins were detectable only in the
      presence of each other in a variety of cell lines, we studied the mechanisms of
      regulation of cellular levels of annexin II and p11. In cells expressing p11
      messenger RNA, p11 protein is undetectable unless annexin II is also expressed.
      As an example, the hepatoblastoma HepG2 cell line displays no detectable annexin
      II nor p11 protein, although it expresses p11 mRNA. The overexpression of annexin
      II by gene transfer into HepG2 cells leads to the up-regulation of the cellular
      levels of p11 by a post-translational mechanism. In the presence of annexin II,
      there is no major change in the p11 transcript levels, but the half-life of the
      p11 protein is increased more than 6-fold. Thus, the degree of expression of
      annexin II, which varies according to different states of cellular
      differentiation and transformation, is an essential factor in the regulation of
      cellular levels of p11.

PMID- 8546710
TI  - Expression of human dopamine beta-hydroxylase in Drosophila Schneider 2 cells.
AB  - Human dopamine beta-hydroxylase (DBH) has been expressed in transformed
      Drosophila Schneider 2 (S2) cells with yields of > 16 mg/l. Most of the activity
      was found in the culture fluid. Similarly, human neuroblastoma cells also secrete
      native DBH into the medium, but at a much lower level than recombinant Drosophila
      cells. We have purified native and recombinant human DBH by a modified
      purification procedure using SP-Sepharose, lentil lectin-Sepharose and gel
      filtration chromatography and carried out studies to compare the two enzymes. Two
      variants of human DBH that differ by a single amino acid (either serine or
      alanine) at position 304 were expressed in Drosophila cells, purified, and found
      to have no significant difference in enzyme activity. The molecular mass of human
      DBH monomer has been determined from SDS/PAGE to be 73 kDa, but the recombinant
      DBH from Drosophila is smaller at 66 kDa. The difference may be due to
      glycosylation as deglycosylated enzymes from both sources are identical in size
      (61 kDa). The Km of tyramine for native and recombinant human enzymes are
      virtually the same but higher than bovine DBH by about 3-fold. Likewise, the
      inhibition of native and recombinant human DBH by fusaric acid and SKF102698 is
      not significantly different but IC50 values are 2-3-fold higher than that for the
      bovine enzyme. These results strongly support the conclusion that recombinant
      human DBH from Drosophila S2 cells can be used in place of human neuroblastoma
      derived DBH for drug screening, characterization of the enzyme's physicochemical
      properties, and determination of structure-function relationships. The Drosophila
      expression system has thus provided a convenient source for large quantities of
      human DBH enzyme.

PMID- 8546711
TI  - Inhibition of mitogen-induced DNA synthesis by bafilomycin A1 in Swiss 3T3
      fibroblasts.
AB  - Quiescent cells (in G0) can be stimulated to enter the cell cycle and proceed to
      DNA synthesis in S-phase by a wide range of growth factors and mitogens.
      Activation of cell-surface growth factor receptors with intrinsic protein
      tyrosine kinase activity initiates autophosphorylation of the receptors and
      subsequent activation of signal transduction cascades. After activation the
      receptors undergo ligand-induced internalization to endosomes, which become
      acidified by the action of a vacuolar H(+)-ATPase (V-ATPase). The extent to which
      vesicular acidification plays a role in mitogenic signalling by receptors with
      intrinsic tyrosine kinase activity remains unknown. Here we have shown that
      bafilomycin A1, a specific inhibitor of V-ATPase, inhibits endosome acidification
      and mitogen-induced DNA synthesis in Swiss 3T3 fibroblasts. Addition of
      bafilomycin A1 at successively later times during G1 progressively decreased the
      inhibition of DNA synthesis such that no inhibition was observed when bafilomycin
      A1 was added at the onset of S-phase. Bafilomycin A1 also induced a dramatic but
      reversible change in the morphology of Swiss 3T3 cells. However, the rapid
      activation of c-fos mRNA accumulation by epidermal growth factor and insulin was
      unaffected by bafilomycin A1. Together, the results suggest that activation of
      the V-ATPase plays an important role in the mitogenic signalling pathways that
      occur during the G1 phase of the cell cycle but is not required for the initial
      epidermal growth factor and insulin-evoked signalling events that lead to c-fos
      mRNA expression.

PMID- 8546712
TI  - The low-density-lipoprotein receptor-related protein (LRP) is processed by furin
      in vivo and in vitro.
AB  - The low-density-lipoprotein receptor-related protein (LRP) is a multifunctional
      receptor involved in the clearance of a large number of diverse ligands,
      including proteases, protease-inhibitor complexes and lipoproteins. The mature
      receptor is composed of a 515 kDa and a 85 kDa subunit generated by proteolytic
      cleavage from a 600 kDa precursor polypeptide in a trans-Golgi compartment.
      Proteolytic processing occurs C-terminal to the tetrabasic amino acid sequence
      RHRR, a consensus recognition site for precursor processing endoproteases or
      convertases. In this study we have identified furin, a subtilisin-type protease,
      to be necessary for efficient processing of LRP in cells. Furin-deficient RPE.40
      cells exhibited an impaired processing of endogenous LRP and of a recombinant
      soluble form of the receptor containing the processing site. The processing
      defect in RPE.40 cells could be complemented by expression of furin from a
      transfected cDNA in cultured cells and by purified furin in vitro. The impaired
      maturation of LRP in RPE.40 cells did not affect its intracellular transport, and
      correlated with a slight but consistent reduction in the endocytosis of LRP
      specific ligands. These data suggest that proteolytic processing of LRP by furin
      is not necessary for intracellular trafficking but might be required for normal
      receptor activity.

PMID- 8546713
TI  - Tumour growth results in changes in placental amino acid transport in the rat: a
      tumour necrosis factor alpha-mediated effect.
AB  - The implantation of a fast growing tumour (Yoshida AH-130 ascites hepatoma) to
      late pregnant rats resulted in no changes in fetal growth, this possibly being
      associated with an important increase in the fetal uptake of maternal-derived
      amino acids [Carbo, Lopez-Soriano and Argiles (1995) Endocrinology 136, 3579
      3584]. The present investigation was undertaken to see whether the presence of
      the tumour induced changes in placental transport systems. For alanine transport,
      although no changes in affinity (Km) were observed, tumour growth resulted in a
      192% increase in Vmax in the Na(+)-independent component. Kinetic analysis of the
      Na(+)-dependent component resulted in two clearly different components: while the
      low-affinity and high-capacity component was unaffected by tumour growth, the
      high-affinity, low-capacity component of the tumour-bearing rats showed an
      important increase in Vmax. (78%). With regard to leucine transport, tumour
      burden induced important increases in the Na(+)-independent component, not only
      in Km (262%) but also in Vmax. (189%). Since elevated tumour necrosis factor
      alpha (TNF) concentrations have been reported in this kind of tumour model, we
      performed the same type of transport experiments in rats chronically treated with
      TNF, the results obtained showing great similarities with those observed with
      tumour growth. The Vmax. of Na(+)-independent alanine transport was also
      increased by the cytokine (104%) while no changes were observed in affinity. TNF
      treatment also induced an increase in the Vmax. (67%) of the Na(+)-dependent
      (high-affinity, low-capacity) component while no changes in affinity were
      observed. Concerning leucine kinetics, TNF treatment, as in the case of tumour
      growth, also increased Km (155%) and Vmax. (72%) associated with Na(+)
      independent transport. Interestingly, treatment with the cytokine increased both
      the Km (43%) and Vmax. (64%) of the Na(+)-dependent component. The inhibition
      patterns suggest the existence of more that one Na(+)-dependent transport for
      alanine although the majority of the amino acid is transported through the A
      system. The results presented suggest that, during gestation, the mother is able
      to adapt her placental amino acid transport systems to compensate for the
      nitrogen drainage associated with tumour growth and thus provide the fetus with
      enough amino acids to allow its normal growth, and that TNF could be responsible
      for the triggering of this compensatory mechanism.

PMID- 8546715
TI  - Maximal epidermal growth-factor-induced cytosolic phospholipase A2 activation in
      vivo requires phosphorylation followed by an increased intracellular calcium
      concentration.
AB  - The 85 kDa cytosolic phospholipase A2 (cPLA2) preferentially catalyses the
      hydrolysis of arachidonic acid from the sn-2 position of phospholipids. cPLA2 can
      be activated by extracellular stimuli such as thrombin, platelet-derived growth
      factor and epidermal growth factor (EGF): A full activation of cPLA2 requires an
      increase of intracellular Ca2+ concentration and phosphorylation on Ser-505 by
      mitogen-activated protein (MAP) kinase. Because EGF can provoke an increase in
      intracellular [Ca2+] ([Ca2+]i) and activation of MAP kinase, we investigated the
      role of these pathways in EGF-induced activation of cPLA2. Characterization of
      two cell lines expressing different numbers of EGF receptors (HERc13 and HER14)
      revealed that both were activating MAP kinase in response to EGF, but only HER14
      responded with an increase in [Ca2+]i. In this study we used both cell lines as a
      tool to clarify the role of each pathway in cPLA2 activation. We show that EGF
      stimulates cPLA2 activity in both cell lines in vitro as measured in cytosolic
      fractions, but only in HER14 in vivo as measured by 3H release from cells
      prelabelled with [3H]arachidonic acid. This latter activation can be restored in
      HERc13 cells by the addition of the ionophore A23187. Interestingly, this effect
      is only observed when EGF stimulation precedes A23187 addition. The
      phosphorylation of MAP kinase, however, was identical under identical conditions.
      We conclude that a maximal cPLA2 activation by EGF requires both, and in this
      order: MAP kinase activation followed by a rise in [Ca2+]i concentration.

PMID- 8546714
TI  - A role for protein phosphorylation in modulating Ca2+ elevation in rabbit
      platelets treated with thapsigargin.
AB  - The effect of modifying protein kinase and phosphatase activity on Ca2+ influx
      induced by inhibition of Ca(2+)-ATPase activity has been investigated in rabbit
      platelets. Activation of protein kinase C (PKC) with phorbol 12-myristate 13
      acetate (PMA) or inhibition of phosphatase type 1/2A (PP1/2A) activity with
      calyculin A caused a dose-dependent inhibition of cytosolic Ca2+ elevation in
      thapsigargin (Tg)-treated platelets and decreased Ca2+ influx into platelets at a
      time when Ca2+ channels had already been opened by pretreatment of cells with Tg.
      In addition, both activation of PKC and inhibition of PP1/2A activity caused a
      dose-dependent inhibition of bivalent cation (Mn2+) influx (acting as a surrogate
      for Ca2+ influx) in Tg-treated platelets. Inhibition of cyclo-oxygenase activity
      caused a small decrease in [Ca2+]i elevation in Tg-treated platelets, but had no
      effect on the ability of PMA or calyculin A to inhibit Tg-induced [Ca2+]i
      elevation Unexpectedly, PMA inhibited Tg-induced [Ca2+]i elevation in the absence
      of extracellular Ca2+, and in agreement calyculin A decreased [Ca2+]i elevation
      almost to basal levels. The results from this study were confirmed with another
      Ca(2+)-ATPase inhibitor, namely 2,5-di(tert-butyl)hydroquinone (tBHQ). These
      findings therefore suggest that modification of phosphorylation of target
      protein(s) on serine/threonine amino acid residues plays a role in the regulation
      of both Ca2+ influx and in the filling state of the intracellular Ca2+ pool in
      platelets treated with Tg.

PMID- 8546717
TI  - Guidelines for the initial evaluation of the adult patient with acute
      musculoskeletal symptoms. American College of Rheumatology Ad Hoc Committee on
      Clinical Guidelines.

PMID- 8546716
TI  - A novel regulatory mechanism for trimeric GTP-binding proteins in the membrane
      and secretory granule fractions of human and rodent beta cells.
AB  - Recently we described roles for heterotrimeric and low-molecular-mass GTP-binding
      proteins in insulin release from normal rat islets. During these studies, we
      observed that a protein with an apparent molecular mass (37 kDa) similar to that
      of the beta subunit of trimeric GTP-binding proteins underwent phosphorylation in
      each of five classes of insulin-secreting cells. Incubation of the beta cell
      total membrane fraction or the isolated secretory granule fraction (but not the
      cytosolic fraction) with [gamma-32P]ATP or [gamma-32P]GTP resulted in the
      phosphorylation of this protein, which was selectively immunoprecipitated by an
      anti-serum directed against the common beta subunit of trimeric G-proteins.
      Disruption of the alpha beta gamma trimer (by pretreatment with either
      fluoroaluminate or guanosine 5'(-)[gamma-thio]triphosphate) prevented beta
      subunit phosphorylation. Based on differential sensitivities to pH, heat and the
      histidine-selective reagent diethyl pyrocarbonate (and reversal of the latter by
      hydroxylamine), the phosphorylated amino acid was presumptively identified as
      histidine. Incubation of pure beta subunit alone or in combination with the
      exogenous purified alpha subunit of transducin did not result in the
      phosphorylation of the beta subunit, but addition of the islet cell membrane
      fraction did support this event, suggesting that membrane localization (or a
      membrane-associated factor) is required for beta subunit phosphorylation.
      Incubation of phosphorylated beta subunit with G alpha.GDP accelerated the
      dephosphorylation of the beta subunit, accompanied by the formation of G alpha
      GTP. Immunoblotting detected multiple alpha subunits (of Gi, G(o) and Gq) and at
      least one beta subunit in the secretory granule fraction of normal rat islets and
      insulinoma cells. These data describe a potential alternative mechanism for the
      activation of GTP-binding proteins in beta cells which contrasts with the
      classical receptor-agonist mechanism: G beta undergoes transient phosphorylation
      at a histidine residue by a GTP-specific protein kinase; this phosphate, in turn,
      may be transferred via a classical Ping-Pong mechanism to G alpha.GDP (inactive),
      yielding the active configuration G alpha.GTP in secretory granules (a strategic
      location to modulate exocytosis).

PMID- 8546718
TI  - Barriers to return to work among persons unemployed due to arthritis and
      musculoskeletal disorders.
AB  - OBJECTIVE: To identify barriers to return to work (RTW) among persons likely to
      be seen in a clinician's practice who are unemployed due to arthritis and
      musculoskeletal disorders. METHODS: Two hundred eighteen persons unemployed due
      to arthritis and musculoskeletal disorders were interviewed at baseline and
      followed up for 1 year, at which time their work status was ascertained. Backward
      stepwise logistic regression was used to determine the association of baseline
      clinical, sociodemographic, and work-related factors to their work status at 1
      year of followup. RESULTS: Fifty-one (24%) of 216 initially unemployed subjects
      had returned to permanent paid employment of > or = 20 hours/week after 1 year.
      Having rheumatoid arthritis, Social Security Disability Insurance (SSDI) status,
      a high pain level, older age, and lower education were barriers to reemployment.
      CONCLUSION: This study establishes the importance of chronic pain and having
      rheumatoid arthritis as factors independently associated with failure to RTW
      among persons unemployed due to arthritis and musculoskeletal disorders. The
      importance of SSDI beneficiary status, age, and education level in RTW is further
      confirmed. Duration of unemployment or previous work factors were not predictors
      of RTW in this group.

PMID- 8546719
TI  - The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis
      synovium.
AB  - OBJECTIVE: To investigate the expressions of co-stimulatory molecules CD86 (B7-2,
      B70) and CD28 by cells obtained from the synovial tissues (ST) and synovial
      fluids (SF) of patients with rheumatoid arthritis (RA). METHODS: Monoclonal
      antibodies (MAb) against CD86 and CD28 were used for immunochemical study of
      synovia from 18 RA patients, 4 osteoarthritis (OA) patients, and 4 normal
      subjects. These MAb were also used for flow cytometry of isolated ST cells from 8
      RA and 5 OA patients and of SF mononuclear cells from 5 RA and 5 OA patients.
      RESULTS: Immunohistochemical examination revealed that CD86+ cells occurred in 11
      of the 18 RA synovia, but in none of the 4 OA or 4 normal synovia. Most of the
      positive cells had macrophage-like morphology, and surrounded lymphoid
      aggregates. Most cells within lymphoid aggregates were stained positively for
      CD28. Flow cytometry showed that CD86+ cells comprised 2.9-33.4% (average 14.3%)
      of the total ST cells and 2.1-14.9% (average 6.1%) of the total SF mononuclear
      cells from RA patients. Approximately 40% of the CD86+ cells expressed CD14. A
      majority (mean 72%, range 57-89%) of the T cells in ST and SF expressed CD28. RA
      synovia expressed more CD86 molecules than did OA synovia (mean frequency of
      positive cells 14.3% versus 2.8%; mean fluorescence intensity 104.6 versus 40.9).

PMID- 8546720
TI  - Synovial tissue macrophage populations and articular damage in rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the relative contribution of individual synovial cell
      populations to polyarticular destruction in rheumatoid arthritis (RA). METHODS:
      Serial measurements of disease activity and articular destruction, obtained
      prospectively in 28 RA patients followed for a mean of 5.8 years, were correlated
      with synovial cell populations quantified using immunohistochemical techniques.
      RESULTS: The mean radiologic score worsened (from 37 to 86; P = 0.0001) despite
      significant improvement in disease activity. Synovial lining layer cell depth and
      sublining layer macrophage, but no lymphocyte, cell counts correlated
      significantly with radiologic course. Detailed analysis of 11 patients
      demonstrated reduced synovial lining expression of CD14 compared with CD68 (P =
      0.003), whereas sublining expression of CD14 and CD68 was equivalent. CONCLUSION:
      Synovial macrophage numbers correlated with articular destruction in RA. In
      addition, the study results provided further evidence that lining layer
      macrophages may represent a distinct subpopulation that is of importance in this
      process. These findings have implications for the development of new therapies
      for RA.

PMID- 8546721
TI  - Responsiveness of human T lymphocytes to bacterial superantigens presented by
      cultured rheumatoid arthritis synoviocytes.
AB  - OBJECTIVE: Type B fibroblastic synoviocytes are abundant in inflamed joints of
      patients with rheumatoid arthritis (RA), and can secrete cytokines and other
      mediators of inflammation. The aim of this study was to determine whether cell
      lines derived from RA type B synoviocytes could also serve as accessory cells for
      T lymphocyte activation. METHODS: Cells from RA synoviocyte lines, with or
      without preculture in interferon-gamma (IFN gamma), were cultured with purified
      peripheral blood T cells, in the presence or absence of superantigens or other
      accessory cell-dependent T cell mitogens. T cell proliferation was measured by
      thymidine incorporation, and synoviocyte surface markers were analyzed by flow
      cytometry. RESULTS: RA type B synoviocyte lines were potent accessory cells for T
      cell responses to bacterial superantigens or lectins, and direct cell-cell
      contact was required. Preculture in IFN gamma augmented synoviocyte expression of
      major histocompatibility complex (MHC) class II molecules and of ligands for some
      T cell costimulatory receptors, but synoviocyte accessory cell function was
      evident even in the absence of IFN gamma. Blocking studies using monoclonal
      antibodies supported the notion of a role CD2, CD11a/CD18 and MHC class II
      molecules in synoviocyte-dependent T cell activation. Monoclonal antibodies
      against IFN gamma, interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis
      factor alpha failed to block the T cell proliferative responses, but anti-IL-2
      was strongly inhibitory. CONCLUSION: Cultured RA and type B synoviocytes can
      perform some of the functions of professional antigen-presenting cells. If such
      cells have similar properties in vivo, they may be important participants in
      activation of immune responses, in addition to their previously described
      synthetic and proinflammatory roles. If RA synovial tissue T cells, like normal
      peripheral blood T cells, can respond to superantigens presented by synoviocytes,
      this interaction could be important in the pathogenesis of RA.

PMID- 8546722
TI  - Cutaneous lymphocyte antigen-positive T lymphocytes preferentially migrate to the
      skin but not to the joint in psoriatic arthritis.
AB  - OBJECTIVE: To investigate whether T cell migration into different sites of
      inflammation (skin and synovium) within the same individual is principally
      regulated by tissue-specific homing or by more general mechanisms related to
      inflammation. METHODS: Expression of cutaneous lymphocyte antigen (CLA) and its
      ligand, E-selectin, was analyzed by immunohistochemistry and immunofluorescence
      using paired skin and synovial membrane (SM) samples from patients with psoriatic
      arthritis (PsA). To investigate disease specificity, delayed-type
      hypersensitivity (DTH) skin lesions, induced by tuberculin purified protein
      derivative, and SM from patients with rheumatoid arthritis (RA), were studied as
      controls. To directly examine cell migration in in vivo, the proportion of CLA+ T
      lymphocytes migrating into suction-induced skin blisters was assessed by flow
      cytometry. Using the same technique, levels of paired peripheral blood and
      synovial fluid (SF) T cells were also analyzed. RESULTS: CLA+ T cells
      preferentially accumulated in the skin, but not in the joint, of patients with
      PsA. Similarly, CLA+ T lymphocytes predominated in the DTH skin lesions of RA
      patients, but were very rare in the SM of RA patients, and were scarcely
      represented in the SF of patients with several chronic inflammatory
      arthropathies. In addition, CLA+ T lymphocytes preferentially migrated into
      epidermal skin blisters. This preferential pattern of CLA+ T cell accumulation
      was not related to the selective expression of E-selectin, since this was similar
      in the skin and SM of both PsA and RA patients. CONCLUSION: The distinct pattern
      of T cell infiltration into sites of inflammation within the skin and synovium is
      regulated by both organ-specific homing and general inflammation-related
      mechanisms.

PMID- 8546723
TI  - Autoantibodies to glycyl-transfer RNA synthetase in myositis. Association with
      dermatomyositis and immunologic heterogeneity.
AB  - OBJECTIVE: To elucidate the clinical significance and immunologic heterogeneity
      of anti-glycyl-transfer RNA (tRNA) synthetase antibodies in
      polymyositis/dermatomyositis (PM/DM). METHODS: Sera from 345 patients with
      rheumatic diseases, including 91 with myositis, were examined using
      immunoprecipitation assays. Autoantibodies to aminoacyl-tRNA synthetases were
      further analyzed with 2-dimensional RNA fractionation and via inhibition of in
      vitro aminoacylation. RESULTS: Serum from 1 patient with DM and interstitial lung
      disease immunoprecipitated glycyl-tRNA synthase along with only 1 of 4 associated
      tRNAs, in comparison with control anti-glycyl-tRNA synthetase antibodies, which
      bound the enzyme along with all 4 associated tRNAs. Immunoblotting findings and a
      lack of in vitro inhibition aminoacylation of tRNA(gly) by serum from this
      patient also suggested differences between the epitope specificity of this serum
      and that of other sera with anti-glycyl-tRNA synthetase antibodies. CONCLUSION:
      This identification of antibodies to glycyl-tRNA synthetase from a patient with
      DM underscores the association of this specificity with the disease. The finding
      that these antibodies bound an epitope outside the active site of the synthetase
      enzyme, in contrast to most anti-aminoacyl-tRNA synthetases, emphasizes the
      immunologic heterogeneity of these autoantibodies.

PMID- 8546724
TI  - The coexistence of systemic sclerosis and rheumatoid arthritis in five patients.
      Clinical and immunogenetic features suggest a distinct entity.
AB  - To elucidate the clinical characteristics and pathogenesis of scleroderma
      rheumatoid arthritis (SSc-RA) overlap syndrome, we analyzed the clinical features
      of 5 patients with SSc-RA overlap. Their HLA phenotypes and genotypes were also
      determined. Generalized skin sclerosis, severe seropositive polyarthritis,
      pulmonary fibrosis, anti-topoisomerase I antibodies, and HLA
      DR4,53;DQA1*0301;DBQ1*04 haplotype were observed in all of the patients. Similar
      clinical features were recognized in most of the 10 cases reported previously.
      Our case studies indicate that SSc-RA overlap may be a distinct entity.

PMID- 8546725
TI  - The antiinflammatory and antiviral effects of hydroxychloroquine in two patients
      with acquired immunodeficiency syndrome and active inflammatory arthritis.
AB  - OBJECTIVE: To report the antiinflammatory and antiviral effects of
      hydroxychloroquine (HCQ) treatment in 2 patients with AIDS and inflammatory
      arthritis. METHODS: Two patients with AIDS and inflammatory arthritis were
      treated with HCQ, which was given in a loading dose of 600 mg/day. The
      maintenance dosage was calculated to remain below 6.5 mg/kg/day. Both patients
      had initial T cell subset studies; 1 patient, had serum and plasma collected
      before and after 1 year of HCQ treatment. Assays were performed for T cell
      subsets, recoverable human immunodeficiency virus type 1 (HIV-1) RNA, mitogen-
      and antigen-specific proliferation, and interleukin-6 (IL-6) levels. New studies
      on the use of HCQ as an anti-HIV-1 agent are reviewed. RESULTS: Both patients had
      a dramatic decrease in their arthritis activity. Neither patient required
      immunosuppressive therapy or developed an opportunistic infection. In the patient
      who was studied after 1 year of therapy, there was a 1-log decrease in
      recoverable HIV-1 RNA, improved mitogen- and antigen-specific immune responses,
      and a large decrease in the IL-6 level while taking HCQ. Recent in vitro and in
      vivo assays in patients with HIV infection have shown similar antiviral and
      antiinflammatory effects from HCQ. CONCLUSION: HCQ may exert simultaneous anti
      inflammatory and antiviral effects in patients with HIV infection and
      inflammatory arthritis. If larger studies confirm this observation, it may be the
      drug of choice in this population of patients.

PMID- 8546726
TI  - Healing phenomena of erosive changes in rheumatoid arthritis patients undergoing
      disease-modifying antirheumatic drug therapy.
AB  - OBJECTIVE: To describe radiographic healing phenomena and reparative changes of
      joint destruction in rheumatoid arthritis (RA). METHODS: Serial radiographs of 6
      patients with erosive RA undergoing long-term treatment with disease-modifying
      antirheumatic drugs (DMARDs) were studied. Radiographs showing healing phenomena
      were reproduced, and examples of single joints are shown. RESULTS: The examples
      show recortication of erosions, filling in of erosions with new bone, and
      secondary osteoarthrosis with bone sclerosis and osteophyte formation. Commonly
      use radiographic scoring methods do not have the capacity to account for these
      reparative changes. CONCLUSION: Healing phenomena can be observed in RA patients
      undergoing long-term DMARD treatment. These phenomena can be regarded as clinical
      end points, and their assessment should be incorporated into existing
      standardized methods for radiologic evaluation and scoring of RA.

PMID- 8546727
TI  - Splinter hemorrhages following arterial puncture.
AB  - Splinter hemorrhages can be a feature of the antiphospholipid syndrome. We
      describe a patient in whom splinter hemorrhages developed following radial artery
      puncture. The implications of this findings in patients with the antiphospholipid
      syndrome are discussed.

PMID- 8546728
TI  - Complete remission of multicentric reticulohistiocytosis with combination therapy
      of steroid, cyclophosphamide, and low-dose pulse methotrexate. Case report,
      review of the literature, and proposal for treatment.
AB  - We describe a patient with multicentric reticulohistiocytosis in whom complete
      remission was achieved by sequential combination therapy with steroid,
      methotrexate, and cyclophosphamide. We reviewed all cases of complete or near
      complete remissions of multicentric reticulohistiocytosis reported in the English
      language literature and propose a new drug regimen for this rare but potentially
      disabling disease.

PMID- 8546729
TI  - Rocky Mountain spotted fever presenting with acute monarticular arthritis.
AB  - This report describes a 30-year-old man who presented with an acute multisystem
      illness which was diagnosed as Rocky Mountain spotted fever (RMSF). Near the time
      of admission the patient was noted to have a newly developed aseptic monarticular
      arthritis of the right knee. The arthritis resolved in association with
      resolution of his systemic illness. To our knowledge, there have been no prior
      reports of acute arthritis in association with RMSF.

PMID- 8546730
TI  - Evaluation of two interventions to reduce the ancillary costs of outpatient care
      for rheumatoid arthritis.

PMID- 8546731
TI  - The paradoxical association between immunodeficiency and autoimmunity: comment on
      the article by Atkinson.

PMID- 8546732
TI  - Treatment of scleroderma lung disease: comment on the article by Steen et al.

PMID- 8546733
TI  - Fibromyalgia or multi-organ dysesthesia?

PMID- 8546734
TI  - Synovial tissue responses following treatment of rheumatoid arthritis with the
      humanized monoclonal antibody CAMPATH-1H.

PMID- 8546735
TI  - The T cell enigma in lupus.

PMID- 8546736
TI  - Development and validation of the European League Against Rheumatism response
      criteria for rheumatoid arthritis. Comparison with the preliminary American
      College of Rheumatology and the World Health Organization/International League
      Against Rheumatism Criteria.
AB  - OBJECTIVE: To validate the European League Against Rheumatism (EULAR), the
      American College of Rheumatology (ACR), and the World Health Organization
      (WHO)/International League Against Rheumatism (ILAR) response criteria for
      rheumatoid arthritis (RA). METHODS: EULAR response criteria were developed
      combining change from baseline and level of disease activity attained during
      follow up. In a trial comparing hydroxychloroquine and sulfasalazine, we studied
      construct (radiographic progression), criterion (functional capacity), and
      discriminant validity. RESULTS: EULAR response criteria had good construct,
      criterion, and discriminant validity, ACR and WHO/ILAR criteria showed only good
      criterion validity. CONCLUSION: EULAR response criteria showed better construct
      and discriminant validity than did the ACR and the WHO/ILAR response criteria for
      RA.

PMID- 8546737
TI  - Oral type II collagen treatment in early rheumatoid arthritis. A double-blind,
      placebo-controlled, randomized trial.
AB  - OBJECTIVE: To investigate the efficacy of oral type II collagen in the treatment
      of early rheumatoid arthritis (RA). METHODS: Ninety patients with RA (disease
      duration < or = 3 years) were treated for 12 weeks with oral bovine type II
      collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in
      a double-blind randomized study. RESULTS: There were no significant difference
      between the 3 groups in terms of response to treatment. However, we observed a
      higher prevalence of responders in the type II collagen-treated groups: 7
      responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4
      in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group
      and 1 patient in the 1-mg type II group, but no patients in the placebo group,
      had very good response. A total of 14 patients had to be withdrawn from the
      study: 2 because of side effects (nausea) and 12 because of lack of efficacy.
      CONCLUSION: Only a minority of patients responded to treatment with oral type II
      collagen. These results justify further efforts to identify which patients will
      have good response to such therapy.

PMID- 8546738
TI  - Percentage of anti-CD4 monoclonal antibody-coated lymphocytes in the rheumatoid
      joint is associated with clinical improvement. Implications for the development
      of immunotherapeutic dosing regimens.
AB  - OBJECTIVE: We assessed the effect of a daily dosing schedule of the chimeric anti
      CD4 monoclonal antibody (MAb), cM-T412, in rheumatoid arthritis (RA) patients,
      and compared lymphocyte changes in the peripheral blood (PB) and synovial fluid
      (SF) of these patients. METHODS: Twelve patients received 50 mg/day of cM-T412
      for 5 days, followed by a maintenance treatment of 50 mg/week for 5 weeks (6
      patients), or a retreatment course of 50 mg/day for 5 days after 5 weeks (6
      patients). Paired PB and SF samples were obtained during treatment for analysis.
      RESULTS: Changes in lymphocyte count and coating with the MAb in PB did not
      reflect changes in the SF. After 5 daily treatments, the percentage of cM-T412
      coated CD4+ lymphocytes in SF correlated with the degree of clinical improvement
      seen in patients at 2 weeks after the initiation of therapy (r = 0.75, P < 0.05).
      CONCLUSION: These results demonstrate the importance of antibody dosage and
      treatment regimen in determining clinical benefit. Our findings suggest that the
      percentage of cM-T412-coated CD4+ lymphocytes in SF may be a predictor of
      clinical outcome.

PMID- 8546739
TI  - Treatment of xerostomia with polymer-based saliva substitutes in patients with
      Sjogren's syndrome.
AB  - OBJECTIVE: To determine the efficacy of 3 types of polymer-based saliva
      substitutes in reducing oral dryness in patients with Sjogren's syndrome (SS).
      METHODS: Subjective efficacy of 3 different saliva substitutes (determined by
      self-administered questionnaire) was evaluated in a double-blind, placebo
      controlled trial in 43 patients with primary and secondary SS. High-viscosity
      versus low-viscosity xanthan gum-based saliva substitutes were also compared in
      33 SS patients. Salivary flow rates (SFR) were determined to examine correlations
      between the SFR and the subjective efficacy of the saliva substitute. RESULTS:
      Neither the saliva substitutes nor the placebo was truly effective. Preference
      for a particular saliva substitute over placebo was equally distributed among the
      3 types of substitutes. The SFR of patients who preferred polyacrylic acid-based
      saliva substitutes was lower than that in patients who preferred the porcine
      mucin-based substitute (P < 0.05). Patients whose oral dryness was reduced by low
      viscoelastic substitutes had a low stimulated SFR ( < 0.20 ml/minute; P < 0.05).
      CONCLUSION: The optimal properties of a saliva substitute are not the same for
      all patients with SS, but are dependent on such parameters as the individual SFR.
      Thus, to determine the best saliva substitute for a particular patient, it is
      necessary to have the patient try a number of substitutes of different
      viscoelastic properties.

PMID- 8546740
TI  - Relationship of running to musculoskeletal pain with age. A six-year longitudinal
      study.
AB  - OBJECTIVE: To determine, by longitudinal study, whether long-distance running,
      maintained for many years, is associated with increased musculoskeletal pain with
      age. METHODS: A 6-year prospective longitudinal study of 410 runners' club
      members and 289 community controls, age 53-75 years at study initiation, was
      conducted. Subjects were also categorized as ever-runners (n = 488) and never
      runners (n = 211). The primary dependent variable was pain score as indicated on
      a horizontal double-anchored analog scale; data for this variable were available
      beginning in 1987. Statistical adjustment for age, education level, smoking,
      alcohol consumption, history of arthritis, and presence of other major medical
      conditions was done by analysis of covariance. Further analyses of previously
      reported associations of regular vigorous physical activity with decreased
      disability and mortality after 9 years were performed. RESULTS: The degree of
      musculoskeletal pain was slightly lower in the exercise group compared with
      controls, and the difference was statistically significant for women but not for
      men. Average adjusted pain scores for men were 18.3 (SEM 0.8) in runners' club
      members, 20.2 (1.2) in controls, 18.6 (0.8) in ever-runners, and 20.3 (1.6) in
      never-runners. For women, these scores were 17.5 (1.8) in runners' club members
      versus 22.8 (1.4) in controls (P < 0.05), and 17.2 in ever runners versus 23.7
      (1.5) in never-runners (P < 0.002). Disability had continued to develop in
      runners' club members at a rate only one-third that in the controls after 9 years
      of observation. Mortality over 9 years consisted of 51 deaths, of which 41 were
      in the control group and only 10 were among runners' club members. CONCLUSION:
      Vigorous running activity over many years is not associated with an increase in
      musculoskeletal pain with age, and there may be a moderate decrease in pain,
      particularly in women. Vigorous physical activity is associated with greatly
      decreased levels of disability and with decreased mortality rates.

PMID- 8546741
TI  - Distal extremity swelling with pitting edema in polymyalgia rheumatica. Report on
      nineteen cases.
AB  - OBJECTIVE: To determine the frequency and clinical characteristics of diffuse
      distal extremity swelling with pitting edema occurring in polymyalgia rheumatica
      (PMR). METHODS: Clinical features and laboratory findings were recorded for all
      245 residents of Olmsted County, Minnesota who developed PMR over a 22-year
      period (1970-1991). Those who exhibited > or = 1 episode of diffuse distal
      extremity edema with pitting were selected for this study, and were evaluated
      further. RESULTS: Thirteen women and 6 men in this incidence cohort of PMR had >
      or = 1 episode of distal extremity swelling with pitting edema. Giant cell
      arteritis was also identified in 5 patients. In 11 patients, the swelling and
      edema development concurrently with proximal PMR symptoms. In 2 patients, the
      distal swelling was the initial manifestation, and in 6 patients, the distal
      symptoms developed during relapses or recurrences of PMR. Both upper and lower
      extremities were affected, usually in a symmetric manner. Other peripheral
      manifestations were also common. The distal swelling and pitting edema responded
      promptly to corticosteroids, and slowly or incompletely to nonsteroidal anti
      inflammatory drugs; a similar response was observed in the proximal symptoms. The
      distal swelling appeared to represent tenosynovitis and synovitis of regional
      structures. CONCLUSION: Distal extremity swelling with pitting edema represents a
      manifestation of PMR that has not been well described in previous studies.
      Awareness of this finding will help facilitate the proper diagnosis and
      institution of appropriate therapy for this disease.

PMID- 8546742
TI  - Association of radiographically evident osteoarthritis with higher bone mineral
      density and increased bone loss with age. The Rotterdam Study.
AB  - OBJECTIVE: To investigate the relationship of osteoarthritis (OA) to bone mineral
      density (BMD) and rate of bone loss. METHODS: The study group consisted of 2,745
      persons (1,624 women) from the general elderly population. Disability was
      assessed by the Health Assessment Questionnaire. Femoral neck BMD was measured at
      baseline and, in 1,723 subjects, after 2 years of followup. Knee and hip
      radiographic OA was assessed on anteroposterior radiographs. RESULTS: With the
      exception of knee radiographic OA in men, radiographic OA was associated with
      significantly increased BMD (3-8%). BMD increased significantly according to the
      number of affected sites and the Kellgren score. Radiographic OA was also
      associated with significantly elevated bone loss with age (in men, only for
      radiographic OA of the hip). A significant increase in relation to the number of
      affected sites and the Kellgren score (except with regard to knee OA in men) was
      found, independent of disability. CONCLUSION: Radiographic OA is associated with
      high BMD and increased rate of bone loss. This suggests a more pronounced
      difference in BMD earlier in life.

PMID- 8546743
TI  - The epidemiology of Wegener's granulomatosis. Estimates of the five-year period
      prevalence, annual mortality, and geographic disease distribution from population
      based data sources.
AB  - OBJECTIVE: To estimate the prevalence, annual mortality, and geographic
      distribution of Wegener's granulomatosis. METHODS: Analysis of national vital
      statistics data and hospitalization data from a national survey and from all New
      York State inpatient facilities. RESULTS: Between 1979 and 1988, 1,784 death
      certificates in the United States listed Wegener's granulomatosis as a cause of
      death. Nationally, an estimated 10,771 hospitalizations included Wegener's
      granulomatosis among the discharge diagnoses. In New York State, there were 978
      hospitalizations among 571 individuals with Wegener's granulomatosis. CONCLUSION:
      The prevalence of Wegener's granulomatosis in the United States is approximately
      3.0 per 100,000 persons. Clear differences in the geographic distribution of
      Wegener's granulomatosis are apparent when analysis consider rates of disease in
      individual counties. Contrary to previous reports, associations between disease
      exacerbations and season were not apparent.

PMID- 8546744
TI  - Pathology and pathogenesis of vascular injury in systemic lupus erythematosus.
      Interactions of inflammatory cells and activated endothelium.

PMID- 8546745
TI  - Cross-cultural adaptation of a brief outcome questionnaire for Spanish-speaking
      arthritis patients.
AB  - OBJECTIVE: To cross-culturally adapt a brief self-assessment questionnaire to
      measure outcome among English- or Spanish-speaking patients with arthritis.
      METHODS: A questionnaire containing the following items was translated to
      Spanish: the 8 activities of daily living (ADL) question of the Modified Health
      Assessment Questionnaire; a question about the duration of morning stiffness; and
      a 10-point pain scale. Equivalence to the original English, test-retest
      reliability, and construct, criterion, and discriminant validity were determined
      on a population of patients with 4 clinical centers. RESULTS: English-Spanish
      equivalence and test-retest reliability of the questionnaire were almost perfect
      (intra-class correlation coefficients [ri] > or = 0.90 for each). Construct
      validity, measured by comparing questionnaire scores with an occupational
      therapist's evaluation, was also near-perfect in both languages (ri = 0.93 for
      English and 0.89 for Spanish). Both versions of the questionnaire correlated well
      with the physician-determined Steinbrocker functional class, as well as with the
      amount of pain, grip strength, and walking velocity. Patients with systemic lupus
      erythematosus, rheumatoid arthritis, osteoarthritis, and fibromyalgia differed
      significantly in their pain:ADL ratios, in both languages. CONCLUSIONS: The items
      of the Spanish questionnaire that we have adapted are equivalent to the original
      English versions. This questionnaire is suitable for studying Spanish-speaking
      subjects with arthritis in the US and elsewhere.

PMID- 8546746
TI  - Serum lipid values in adolescents are related to family history, infant feeding,
      and physical growth.
AB  - Total serum cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I
      (apo A-I), apolipoprotein B (apo B), and lipoprotein (a) (Lp(a)) were analysed in
      879 14- and 17-year-old healthy adolescents (477 boys and 402 girls), and related
      to family history of cardiovascular disease, early feeding, weight and length at
      birth, and physical growth during infancy and childhood. Mean TC was
      significantly higher in girls than in boys (4.4 and 4.2 mmol/l, respectively,
      both age-groups together). High TC values ( > 5.2 mmol/l) were more prevalent in
      girls than in boys: 14% and 17% compared to 6% and 12% in 14- and 17-year-old
      girls and boys, respectively. Mean TC and LDL-C values were lower during mid
      puberty in both boys and girls while, in boys but not in girls, mean HDL-C values
      decreased and TG values increased successively with increasing pubertal stage.
      Girls who were taking oral contraceptives had higher mean values of TC (4.91/4.39
      mmol/l), TG (1.32/0.83 mmol/l), and apo B (0.89/0.73 g/l). Boys with a family
      history of early deaths ( < 55 years) from myocardial infarction and girls with a
      family history of cerebral haemorrhage/thrombosis in fathers had higher mean
      values of TC (4.55/4.17 and 5.03/4.40 mmol/l, for boys and girls, respectively),
      LDL-C (2.84/2.47 and 3.08/2.56 mmol/l), and apo B (0.73/0.70 and 0.86/0.73 g/l).
      Adolescents with short duration of breast feeding ( < 6 months), or early
      introduction of infant formula, had higher mean values of TC (4.29/4.14 mmol/l)
      and apo B (0.72/0.68 g/l). There were no significant correlations between serum
      lipid values and body weight or length at birth, but adolescents with high LDL-C
      (upper quartile) seemed to have lower attained heights during infancy and
      childhood. In conclusion, this study shows that serum lipids in adolescence are
      primarily related to age and sex but also to early determinants like family
      history of cardiovascular diseases, infant feeding, and early physical growth.

PMID- 8546747
TI  - Risk factors for coronary heart disease in the prospective Dubbo Study of
      Australian elderly.
AB  - A new prospective study of non-institutionalised Australian elderly 60 years and
      over commenced in Dubbo in 1988, comprising 1236 men and 1569 women. This report
      examines clinical and socio-demographic predictors of coronary heart disease
      (CHD) over a median 62 months follow-up. CHD incidence rates (ICD-9-CM codes 410
      414) were higher in men than women until 79 years, thereafter, the rates for
      recurrent disease were higher in women. Incidence rates for recurrent disease
      were three-fold those for initial disease. In Cox proportional hazards analysis,
      the significant predictors of all CHD were: advancing age, prior CHD (relative
      risk (RR) = 2.50 and 2.15 in men and women, respectively), use of anti
      hypertensive medication (RR = 1.92 and 1.75 in men and women, respectively).
      diabetes (RR = 1.67 and 1.53 in men and women, respectively), serum cholesterol,
      low density lipoprotein cholesterol and serum apo B in men (RR = 1.24), serum
      triglycerides in women (RR = 1.23), high density lipoprotein cholesterol in men
      (RR = 0.82), lipoprotein (a) in women (RR = 1.99), and poorer self-rating of
      health (RR =1.48 and 1.93 in men and women, respectively). Serum cholesterol was
      not predictive of CHD in men beyond 74 years. Isolated systolic hypertension
      predicted CHD in women (RR = 3.76), but not in men (RR = 1.20). The findings
      highlight key risk factors for CHD in the elderly.

PMID- 8546748
TI  - Lymphocyte T subset counts in children with elevated low-density lipoprotein
      cholesterol levels.
AB  - The aim of this study was to determine blood lymphocyte T subset counts in
      children with elevated levels of low-density lipoprotein cholesterol. We studied
      107 children, ages 2.0 to 15.9 years, from 79 families who were referred to our
      Lipid Research Clinic because total cholesterol serum levels higher than 200
      mg/dl had been detected in at least one child. At the time of diagnosis we
      analyzed serum lipoprotein profile and blood lymphocyte T subsets (CD3, CD4 and
      CD8). Children were classified according to LDL-C levels into three groups: (1)
      normal, if levels were between the 5th and 75th percentiles (50 and 125 mg/dl,
      respectively); (2) at moderate risk, if levels were between the 75th and 95th
      percentiles (125 and 150 mg/dl, respectively); and (3) at high risk, if levels
      were above the 95th percentile (150 mg/dl). In children aged 2.0 to 6.9 years,
      all lymphocyte T subset counts were higher in the high risk group than in the
      normal group (P < 0.05 and P < 0.01). In children aged 11.0 to 15.9 years, the
      CD4 subset count was also significantly higher in the high risk group in the
      other two groups (P < 0.05 and P < 0.01). These results are in agreement with
      pathologic findings in the atheromatous plaque.

PMID- 8546749
TI  - 1,25-Dihydroxyvitamin D3-induced HL-60 macrophages: regulation of cholesterol and
      LDL metabolism.
AB  - Differentiation of human promyelocytic leukemic HL-60 cells with 1,25
      dihydroxyvitamin D3 (D3) results in macrophages which exhibit specific and
      saturable receptor-mediated processing of both native and modified low density
      lipoprotein (LDL). Analysis of binding kinetics demonstrated that macrophages
      bind LDL and acetyl-LDL with similar affinities, yet possess significantly
      different numbers of receptors (55 +/- 6 x 10(3) LDL receptors/cell vs 79 +/- 7 x
      10(3) acetyl-LDL receptors/cell). D3-induced HL-60 macrophages challenged with
      LDL or acetyl-LDL exhibited suppression of HMG-CoA reductase activity as well as
      a significant induction in the incorporation of [14C]oleate into cholesteryl
      ester compared with macrophages incubated with lipoprotein depleted serum.
      Maximum increases in ACAT activity were obtained in macrophages incubated with 25
      hydroxycholesterol plus LDL or acetyl-LDL. The increase in ACAT activity in
      macrophages challenged with acetyl-LDL paralleled the increase in cellular
      cholesterol content and the increase of oil red O lipid stainable material,
      imparting the macrophages with a foamy appearance. The data indicate that D3
      induced HL-60 macrophages are a useful model for the study of lipoprotein-
      macrophage interactions as related to foam cell development and atherogenesis.

PMID- 8546750
TI  - Dialysis of isolated low density lipoprotein induces a loss of lipophilic
      antioxidants and increases the susceptibility to oxidation in vitro.
AB  - We determined the effects of different dialysis conditions on the antioxidant
      content, duration of the lag phase and oxidation rate of LDL. Dialysis for 22 h
      resulted in a 56%--66% reduction in the concentrations of beta-carotene, lycopene
      and alpha-tocopherol. The lag phase of copper-induced oxidation of freshly
      isolated LDL was considerably longer than that of LDL dialysed for 22 or 44 h.
      Our data show that dialysis may result in LDL preparations with antioxidant
      compositions that are not truly representative of freshly isolated lipoproteins.

PMID- 8546751
TI  - Hepatic apolipoprotein and LDL receptor gene expression in the genetically
      hypercholesterolemic (RICO) rat.
AB  - The present study was designed to examine apolipoprotein and LDL receptor gene
      expression in genetically hypercholesterolemic RICO rats. In the plasma of RICO
      rats as compared to SW (control) rats, the hypercholesterolemia (+41%) was
      associated with a significant increase in plasma apo B (+23%) and apo E (+68%)
      concentrations. Study of apolipoprotein synthesis in the liver has shown that
      this increase in plasma apo B and apo E concentrations was not associated with
      modification in their synthesis and mRNA levels. Study of apo E mRNA level in
      various tissues has shown only the modification in adrenals in RICO as compared
      to SW rats (2.7-fold increase). Study of LDL binding, LDL receptor mass and LDL
      receptor mRNA level in the liver of RICO and SW rats has shown no significant
      differences between these two strains. EDTA-resistant binding of rat LDL was
      lower in RICO than in SW rats suggesting that binding sites others than the LDL
      receptor are present in lesser amount in this hypercholesterolemic strain.

PMID- 8546752
TI  - Low density lipoprotein oxidation is inhibited in vitro by olive oil
      constituents.
AB  - Oxidation of low density lipoproteins maybe a factor in the development of
      atherosclerosis. The Mediterranean diet rich in vegetables, grains, legumes,
      fruits, and oils, mainly olive oil, has been suggested to reduce the incidence of
      coronary heart disease, because of its low saturated and high monounsaturated
      fatty acids content. It is also possible that the natural antioxidants in the oil
      help to prevent lipid oxidation, e.g. that of low density lipoproteins, thus
      retarding the formation of atherosclerotic plaques. First-pressed, extra-virgin
      olive oil contains appreciable amounts of polyphenolic compounds that prevent its
      autoxidation and are responsible for its high stability. We tested these
      compounds on low density lipoprotein oxidation and found an inhibitory effect, at
      low concentrations, on various indexes of lipid oxidation (vitamin E content,
      formation of thiobarbituric acid-reacting substances, lipid peroxides, levels of
      polyunsaturated fatty acids, protein modification, conjugated diene formation).
      Our data suggest that natural antioxidants could play a role in inhibiting the
      formation of cytotoxic products such as lipid peroxides thus retarding the onset
      of the atherosclerotic damage.

PMID- 8546753
TI  - Racial variation of factor VII activity and antigen levels and their correlates
      in healthy Chinese and Indians at low and high risk for coronary artery disease.
AB  - Plasma factor VII activity (FVIIc) is one of the independent risk factors of
      coronary artery disease (CAD) and is controlled by both genetic and environmental
      factors. South Asians including Indians have one of the highest prevalence and
      mortality rates from CAD while the Chinese have a much lower risk. Generally
      accepted risk factors cannot explain the high mortality from CAD in Indians. We
      examined two hundred and seventy seven Chinese (124 m, 153 f); and 216 healthy
      Indian (150 m, 66 f) adults for serum lipids; plasma FVIIc and FVIIag levels in
      order to examine racial variations of these and their correlates in these two
      populations. Both Indian men and women had significantly higher FVIIc levels (12%
      and 11%, respectively) than the Chinese even after adjustments of age, BMI and
      lipids (P < 0.01). In contrast, Indians had significantly lower plasma FVIIag
      levels than Chinese (8% and 9%, respectively in men and women; P < 0.01).
      Multiple linear regression analysis shows a strong correlation of FVIIc with
      serum triglycerides accounting for 4-8% of the total variability of FVIIc in
      different groups. Further, there was a stronger correlation between FVIIc and
      FVIIag in Indians than that in the Chinese (0.43 vs. 25) suggesting a greater
      activation resulting in higher FVIIc in Indians inspite of lower FVIIag levels.
      The higher FVIIc and stronger activation by triglycerides observed in this study
      partly explain the higher risk of CAD in Indians.

PMID- 8546754
TI  - Association of polymorphisms of the apolipoprotein B gene with coronary heart
      disease in Han Chinese.
AB  - Four polymorphic sites of the apolipoprotein B (apo B) gene were investigated by
      using polymerase chain reaction (PCR) in 103 patients with coronary heart disease
      (CHD) and 100 age-matched healthy individuals selected from a population of Han
      Chinese in the Beijing area. The rare X+ allele of the XbaI restriction site was
      more frequently seen in CHD patients than in controls (0.088 vs. 0.025, P <
      0.01). The relative frequency of rare E- allele of the EcoRI restriction site was
      significantly higher in CHD patients compared with controls (0.11 vs. 0.04, P <
      0.01). Similarly, 3'VNTR-L allele (number of repeat units > 39) at the VNTR
      region was also present at an apparently high frequency in CHD patients in
      comparison to that in controls (0.602 vs. 0.290, P < 0.001). However, the
      difference in relative frequency of rare Del allele of the Ins/Del polymorphism
      at the signal peptide was not significant between the two groups (0.282 vs.
      0.235. P > 0.05). In comparison with Caucasians, the relative frequencies of rare
      alleles (Del, X+ and E-) were found to be statistically lower in Han Chinese.
      Furthermore, the Del and X+ alleles, in linkage disequilibrium, were associated
      with significantly lower plasma level of HDL-C in CHD patients. Therefore it is
      suggested that genetic variation with the apo B gene may exert some impact on
      lipid metabolism and contribute to the susceptibility to development of CHD in
      Han Chinese.

PMID- 8546755
TI  - Ovariectomy decreases plasma triglyceride levels in analbuminaemic rats by
      lowering hepatic triglyceride secretion.
AB  - In mutant analbuminaemic rats (NAR), females demonstrate a more marked
      hypertriglyceridaemia than males. Ovariectomy decreases triglyceride levels in
      female NAR. We measured triglyceride secretion rates in vivo as well as the
      activity of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) in hepatic
      cytosol obtained from female control Sprague-Dawley (SD) rats and NAR with or
      without ovariectomy. NAR were severely hyperlipidaemic, and triglyceride,
      cholesterol, apolipoprotein A-I and plasma protein concentrations levels were
      decreased (all P < 0.01) by ovariectomy. Only triglyceride levels were decreased
      by ovariectomy in the SD rats (P < 0.05). Oestradiol treatment in ovariectomized
      NAR restored plasma protein and triglyceride concentrations to levels similar to
      those observed in intact female NAR and caused a marked increase in plasma
      cholesterol. Ovariectomy in NAR reduced lipoprotein triglycerides and cholesterol
      in VLDL, IDL and LDL1, but had little effect on the triglyceride-cholesterol
      ratio of these particles. Both ACC and FAS activities were markedly increased in
      NAR vs. SD rats (P < 0.01). This increase was partially corrected by ovariectomy.
      There was no significant effect of ovariectomy on ACC or FAS activity in the SD
      rats. Triglyceride secretion rates were significantly increased in NAR vs. SD
      rats (135 +/- 10 vs. 103 +/- 12 nmol/min per 100 g body weight; P < 0.05).
      Ovariectomy markedly decreased triglyceride secretion rate in NAR to 69 +/- 6 (P
      < 0.01), but not in SD rats (92 +/- 8 nmol/min per 100 g body weight, NS).
      Oestradiol treatment in ovariectomized SD rats restored triglyceride levels but
      had no significant effect on triglyceride secretion rate (106 +/- 23 nmol/min per
      100 g).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8546756
TI  - Evaluation of oxidative stress in patients with hyperlipidemia.
AB  - An antioxidant defense system consisting of enzymes and non-enzymatic compounds
      prevents oxidative damage of lipoproteins in the plasma. When the activity of
      this system decreases or the reactive oxygen species (ROS) production increases,
      an oxidative stress may occur. Since fatty acids and triglyceride-rich emulsions
      can stimulate leukocytes to produce ROS, it is conceivable that raised plasma
      triglyceride-rich lipoproteins such as very low density lipoprotein (VLDL) may
      overload the antioxidant system. To test this hypothesis, we selected 14 patients
      with combined hyperlipidemia (HLP), in whom low density lipoprotein (LDL) and
      VLDL levels are elevated, as well as 18 hypercholesterolemic patients (HCH) with
      increased LDL levels and 19 controls (NL) to examine the trend for an imbalance
      between the production of oxidative species and the antioxidant defense system as
      challenged by increased plasma lipids. With this goal, plasma lipoprotein lipid
      fractions were determined and correlated with the release of ROS by leukocytes
      monitored by luminol-enhanced chemiluminescence. Plasma beta-carotene, alpha
      tocopherol, lycopene and the lipoprotein lipid hydroperoxides were determined by
      high pressure liquid chromatography with electrochemical detection. HLP had lower
      plasma superoxide dismutase (SOD) activity (0.04 and 0.11 U/mg protein; P < 0.05)
      as well as lower concentrations of lycopene (0.1 and 0.2 nmol/mg cholesterol; P <
      0.05) and beta-carotene (0.8 and 2.7 nmol/mg cholesterol; P < 0.05) in the
      plasma, as compared with NL. Moreover, HLP showed the highest ROS production by
      resting mononuclear leukocytes (MN) among the three study groups. When the
      results of the subjects of the three groups were taken together, the plasma
      triglyceride concentration was positively correlated to ROS release by resting
      polymorphonuclear leukocytes (PMN, r = 0.38, P = 0.04) and MN (r = 0.56, P <
      0.005). Moreover, ROS release by resting MN was positively correlated with VLDL
      (r = 0.47, P = 0.02) and LDL (r = 0.57, P = 0.01) triglycerides. There was also a
      positive correlation between ROS release by stimulated PMN and VLDL (r = 0.44, P
      = 0.03) as well as LDL (r = 0.53, P = 0.01) triglycerides. High density
      lipoprotein (HDL) cholesterol showed a negative correlation with ROS release by
      resting MN (r = -0.48, P = 0.02) and resting PMN (r = -0.49, P = 0.01). VLDL
      susceptibility to copper (II) oxidation was not different among the three groups.
      Regarding LDL, there was an increased oxidizability in HLP group.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8546757
TI  - Genetic effect of apolipoprotein(a) and apolipoprotein E polymorphisms on plasma
      quantitative risk factors for coronary heart disease in American black women.
AB  - The distributions of plasma total cholesterol, apolipoproteins A-I and B and
      lipoprotein(a) levels as well as genetic typings of apolipoprotein(a) and
      apolipoprotein E were determined in a randomly selected sample of American Black
      women (mean age 22.2 +/- 6.5 years) . Mean plasma levels of cholesterol,
      apolipoprotein A-I, apolipoprotein B and lipoprotein(a) were 184.5 +/- 3.0 mg/dl,
      138.0 +/- 3.1 mg/dl, 79.5 +/- 1.8 mg/dl and 24.5 +/- 1.5 mg/dl, respectively.
      Plasma lipoprotein (a) levels correlated significantly with apolipoprotein B and
      cholesterol. The contribution of apolipoprotein (a) and apolipoprotein E
      polymorphisms in affecting these quantitative traits was evaluated. The
      apolipoprotein(a) locus was extremely polymorphic with 27 alleles, while the 3
      common alleles were observed in the apolipoprotein E gene. The frequencies of the
      APOE*2, APOE* and APOE*4 alleles were 0.094, 0.674 and 0.232, respectively. An
      inverse relationship was observed between the size of apolipoprotein(a) isoforms
      and lipoprotein(a) levels (r = 0.37; P = 0.0001). The apolipoprotein E
      polymorphism revealed a significant genotypic effect on apolipoprotein B (P =
      0.0008) and cholesterol (P= 0.005) levels; these concentrations were lower in the
      APOE 2-3 genotype and higher in the 3-4 and 4-4 genotypes compared with the
      common 3-3 genotype. The apolipoprotein E polymorphism explained 15.8% and 6.3%
      of the phenotypic variance in apolipoprotein B and cholesterol levels,
      respectively. This study demonstrates that genetics play an important role in
      determining quantitative risk factors for coronary heart disease among American
      Black women.

PMID- 8546758
TI  - Kinetics of smooth muscle cell proliferation and intimal thickening in a pig
      carotid model of balloon injury.
AB  - Restenosis as a result of neointimal smooth muscle cell accumulation is an
      important limitation to the effectiveness of balloon angioplasty as a treatment
      for end-stage atherosclerosis. Quantitative animal models allow the definition of
      pathophysiological mechanisms and the evaluation of new therapeutic strategies.
      In this study we quantified the time course of neointima formation by
      morphometry, and smooth muscle cell (SMC) proliferation by immunocytochemistry
      for proliferating cell nuclear antigen (PCNA), in the pig carotid artery 0-28
      days following balloon injury. This led to two distinct kinds of injury observed
      also in clinical studies, namely medial dilatation or deep medial tearing with
      rupture of the internal elastic lamina. Dilatation injury alone led to medial
      enlargement and neointima formation by 7 days, which did not increase further up
      to 28 days. Medial enlargement was similar following rupture of the internal
      elastic lamina; however the sum of neointima formation plus the area of medial
      repair ('neomedia') increased progressively up to 21 days after balloon injury.
      Balloon injury increased the PCNA index of smooth muscle cells in the media
      underlying an intact internal elastic lamina maximally after 3 days. The PCNA
      index in the neointima and especially in the neomedia was greater and maximal
      after 7 days. Endothelial regrowth occurred by 21 days in the presence or absence
      of medial tears. Our results establish a quantitative pig model of balloon injury
      which will allow the assessment of new therapeutic strategies directed at two
      clinically relevant types of injury. Medial tearing is associated with an
      enhanced and localized proliferative response and may therefore be especially
      important in human restenosis.

PMID- 8546760
TI  - Research in Medical Education. Proceedings of the 34th annual conference.
      Washington, D.C., October 31-November 1, 1995.

PMID- 8546759
TI  - FK409, a new nitric-oxide donor, suppresses smooth muscle proliferation in the
      rat model of balloon angioplasty.
AB  - The effect of FK409, a new nitric-oxide (NO) donor, on neointimal formation of
      rat carotid arteries following balloon injury was studied. The intimal thickening
      at 14 days was strongly suppressed by twice daily administration of FK409 at 10
      mg/kg from 2 days before to 13 days after injury. The neointima area and
      neointima/media ratio were decreased by 48.0% (P < 0.01) and 38.5% (P < 0.01),
      respectively, compared with control. On the other hand, isosorbide dinitrate
      (ISDN), a classical nitro-vasodilator, did not suppress intimal thickening even
      at 100 mg/kg twice a day. An in vivo 5-bromo-2'-dedoxyuridine (BrdU) uptake study
      revealed that FK409 inhibited the proliferative response of smooth muscle cells
      (SMC) in media at early stage of injury. In fact, the neointimal formation at 14
      days was inhibited by the short term administration of FK409 only from the day of
      injury to 4 days after at 10 mg/kg twice a day. In cultured rat SMC, FK409 (1-10
      mumol/l) markedly enhanced intracellular c-GMP and inhibited the proliferation in
      10% FBS-containing medium. These results suggest that FK409 suppresses intimal
      thickening following balloon injury of the rat carotid artery by inhibition of
      SMC proliferation.

PMID- 8546761
TI  - Standardized patients as a measure of change in the ability of family physicians
      to detect and manage alcohol abuse.

PMID- 8546762
TI  - Further evidence of the relationship between case typicality and diagnostic
      performance: implications for medical education.
AB  - We have produced further evidence demonstrating that DDx performance is a
      function of a test case's typicality. Medical educators might consider exploring
      how cognitive scientists have used the typicality assumption to investigate and
      enhance the instruction and assessment of subjects engaged in other
      classification tasks. Further substantiation of the applicability and utility of
      the assumptions making up the abstraction and exemplar theories used to explain
      DDx performance could serve as the basis for effective and efficient curricular
      reforms in medical education.

PMID- 8546763
TI  - Developing a presentation and problem-solving station in a multistation
      standardized-patient examination.

PMID- 8546764
TI  - Development of clinical reasoning exercises in a problem-based curriculum.

PMID- 8546765
TI  - Impact of feature interpretation on medical student diagnostic performance.

PMID- 8546766
TI  - A comparison of short- and long-case stations in a multiple-station test of
      clinical skills.

PMID- 8546767
TI  - Sexual harassment in medical education: a review of the literature with comments
      from the law.

PMID- 8546768
TI  - Reform in medical education: a health of the public perspective.

PMID- 8546769
TI  - Learning pulmonary physiology: comparison of student and faculty knowledge
      structures.

PMID- 8546770
TI  - Differences in knowledge representations of experienced and inexperienced
      clinicians as captured by repertory grids.

PMID- 8546771
TI  - Large-scale high-stakes testing with an OSCE: report from the Medical Council of
      Canada.

PMID- 8546772
TI  - Analysis of the psychometric properties of eight administrations of an objective
      structured clinical examination used to assess international medical graduates.

PMID- 8546773
TI  - Preliminary study of the accuracies of the old and new medical college admission
      tests for predicting performance on USMLE Step 1.

PMID- 8546774
TI  - Relationship between achievement in basic science coursework and performance on
      1994 USMLE Step 1. 1994-95 Validity Study Group for USMLE Step 1/2 Pass/Fail
      Standards.

PMID- 8546775
TI  - The relationship between clinical science performance in 20 medical schools and
      performance on Step 2 of the USMLE licensing examination. 1994-95 Validity Study
      Group for USMLE Step 1 and 2 Pass/Fail Standards.

PMID- 8546776
TI  - Examinees' perceptions of factors influencing their performance on USMLE Step 2.

PMID- 8546777
TI  - Medical school applicants' essays as predictors of primary care career choice.

PMID- 8546778
TI  - Diagnostic accuracy and likelihood estimations of attending physicians and house
      officers.

PMID- 8546779
TI  - Reliability and validity of interviewers' judgments of medical school candidates.

PMID- 8546780
TI  - Still-frame simulations of cardiac motion studies: validity evidence from the
      cardiovascular disease certification examination.

PMID- 8546781
TI  - The relationship between training program characteristics and scores on the
      cardiovascular disease certification examination.

PMID- 8546782
TI  - Use of a standardized-patient-based clinical performance examination as an
      outcome measure to evaluate medical school curricula.

PMID- 8546783
TI  - Students' perceptions about their courses in problem-based-learning and
      conventional curricula.

PMID- 8546784
TI  - Global rating scales in residency education.

PMID- 8546785
TI  - Professional and personal characteristics of graduates as outcomes of differences
      between combined baccalaureate--MD degree programs.

PMID- 8546786
TI  - Using attribution theory models to predict senior medical students' perceptions
      of patients and career choice.

PMID- 8546787
TI  - An evaluation of the efficacy of interactive videoconferencing in residency and
      continuing education.

PMID- 8546788
TI  - Self-reported cheating by students at one medical school.

PMID- 8546790
TI  - An innovative evaluation method in an internal medicine clerkship.

PMID- 8546789
TI  - The effect of early performance on examiners' marking patterns during an oral
      examination.

PMID- 8546791
TI  - Dimensions of feedback in clinical teaching: a descriptive study.

PMID- 8546792
TI  - Validity of standardized-patient examination scores as an indicator of faculty
      observer ratings.

PMID- 8546793
TI  - Validity of simple approach to scoring and standard setting for standardized
      patient cases in an examination of clinical competence.
AB  - The results are disappointing, providing little support for the validity of the
      case-passing decisions based on this simple approach to scoring and standard
      setting. The case-passing decisions predicted what the case author intended for
      about only 73% or 74% of the students on average and, with agreement expected by
      chance removed, predicted what the case author intended for about only 25% of the
      students. Even with the use of the optimal pass/fail cutoffs and the dropping of
      students with ambiguous borderline global ratings, the case-passing decisions
      failed to agree with the case authors' global ratings for 15% to 30% of the
      students. The findings might be dismissed as simply due to low reliabilities of
      passing decisions and global ratings based on a single case. Although this
      concern would apply to intercase reliabilities, which would be subject to case
      specificity, the appropriate reliabilities here would seem to be intracase (i.e.,
      intrarater), which should be fairly high (if they could be computed).
      Nevertheless, it seems reasonable to expect much better agreement between results
      of case scoring and of standard setting developed by the case author and the case
      author's global ratings of performance on that case, given that the case author
      might recall the checklist, assign a weight to each item, and so forth. Also,
      case-passing decisions would possibly agree more with global ratings of live or
      videotaped performances than with ratings of written summaries of performance;
      however, that question remains a challenge for further research. In conclusion,
      the study provides only weak evidence, at best, for the validity of the scoring
      and standard setting commonly used with SP assessment. The results do not
      undermine claims about the realism of the SP approach, however, nor do they call
      into question the standardization afforded by this method of assessing clinical
      competence. The results do raise serious concerns about this simple approach to
      scoring and standard setting for SP-based assessments and suggest that we should
      focus more on the observation and evaluation of actual student performance on SP
      cases in the development of valid scoring and standard setting.

PMID- 8546794
TI  - Psychometric properties of a standardized-patient checklist and rating-scale form
      used to assess interpersonal and communication skills.
AB  - The results show that the SP checklist scores and the SP ratings of interpersonal
      and communication skills have comparable psychometric properties. The
      reliabilities of the five-item rating form (.76) and the single global rating of
      patient satisfaction (.70) were slightly higher than the reliability of the 17
      item checklist (.65); this finding is of particular significance, given the
      greater length of the checklist. Also, the checklist scores and ratings appear to
      be measuring the same underlying dimension, with correlations of the checklist
      with the five ratings and with the single global rating being .82 and .81,
      respectively. Van der Vleuten and associates, in two excellent articles, noted a
      recent shift away from the use of subjective measures of clinical competence,
      such as rating scales, toward the use of presumably more objective measures, such
      as SP checklists. Their concern was that these objective measures may focus on
      somewhat trivial and easily measured aspects of the clinical encounter, and that
      more subtle but critical factors in clinical performance may be overlooked or
      ignored. They referred to such measurement as "objectified" rather than
      objective. The shift is based on the presumption that objective or objectified
      measurement is superior to subjective measurement, such as ratings, with respect
      to psychometric properties such as reliability. On the basis of a survey of
      several studies, though, the authors concluded that "objectified methods do not
      inherently provide more reliable scores" and "may even provide unwanted outcomes,
      such as negative effects on study behavior and triviality of the content being
      measured." The results of the present study support this conclusion, showing
      somewhat higher reliabilities for subjective ratings than for the objective (or
      perhaps objectified) checklist. Also, the high uncorrected correlations suggest
      that the more reliable ratings are measuring the same underlying dimension as are
      the checklist scores. The present study also illustrates the application of a
      recently proposed method for constructing a valid SP checklist, which would
      consist of items that best reflect global ratings of performance. In this study,
      the ratings were provided by the SPs themselves, but ratings could be obtained
      from faculty-physician experts who observe student performance on the SP case.
      Thus, performance on individual checklist items would be correlated with expert
      ratings, to identify the items that best predict the ratings. The checklist,
      then, would be constructed of just those items that best predict the ratings, and
      the checklist could be used for future testing without the need for further
      faculty ratings (yet the checklist scores would reflect the faculty ratings).
      With this approach, it would seem possible to construct checklists for history
      taking and physical-examination skills, as well as for interpersonal and
      communication skills. Thus, the faculty ratings would provide a basis for case
      development and refinement, including scoring and standard setting, and scores on
      the checklist would serve as a proxy for the gold-standard faculty ratings. The
      study suggests that SP ratings may be more efficient and more reliable than SP
      checklists for assessing interpersonal and communication skills. The study also
      demonstrates that global ratings by SPs (or by expert physician observers) can
      provide a basis for SP-test construction.

PMID- 8546795
TI  - Are fully compensatory models appropriate for setting standards on performance
      assessments of clinical skills?

PMID- 8546796
TI  - Sleep deprivation in senior medical students and first-year residents.

PMID- 8546797
TI  - A model smoking-intervention curriculum for medical school.

PMID- 8546798
TI  - Consequences of shifting medical-student education to the outpatient setting:
      effects on performance and experiences.

PMID- 8546799
TI  - The viral-autoimmunity relationship.

PMID- 8546800
TI  - A highly divergent antigenic site of foot-and-mouth disease virus retains its
      immunodominance.
AB  - The ability of a highly divergent antigenic site of foot-and-mouth disease virus
      (FMDV) of serotype C to elicit neutralizing antibodies has been evaluated in mice
      and rabbits. The viruses compared, FMDV C-S8c1 and HR, differ in a single amino
      acid replacement in their capsid proteins, but represent two extreme antigenic
      specificities of the major antigenic site A of FMDV type C. Both, studies of
      cross-neutralization of homologous and heterologous virus, and fractionation of
      site A-specific antibodies by immunoaffinity chromatography suggest a similar
      immunodominance of antigenic site A in FMDV C-S8c1 and variant HR. This
      information is relevant to the formulation of synthetic peptide vaccines that
      ideally should consist of mixtures of peptides representing several antigenic
      specificities. These cocktail formulations may be required to control diseases
      caused by FMDV and, generally, by highly variable RNA viruses, since single
      specificity peptides may trigger selection of vaccine-escape viral mutants.

PMID- 8546801
TI  - Lymphocyte proliferative responses to recombinant bovine herpes virus type 1 (BHV
      1) glycoprotein gD (gIV) in immune cattle: identification of a T cell epitope.
AB  - The lymphocyte proliferative response to BHV-1 in immune cattle was compared to
      recombinant wild-type gD and truncated gD produced from recombinant vaccinia
      viruses. The response exhibited by recombinant proteins was comparable to the
      response induced by BHV-1 suggesting that gD is the major target structure for
      stimulation of bovine lymphocytes. Analysis of the proliferative response using
      vaccinia virus vectors expressing various modified forms of gD identified a
      region between residues 165 and 216 recognized by T-lymphocytes of immune cattle.
      Further analysis by overlapping peptides in this region localized the T cell
      epitope to residues 161-172. Antibody-blocking studies demonstrated that
      lymphocytes responding to this epitope are CD4+. In addition, lymphocytes
      stimulated with gD or peptide 77 (residues 161-172) also produced IFN-gamma and
      IL-2.

PMID- 8546802
TI  - Loss of Gag-specific antibody reactivity in cattle experimentally infected with
      bovine immunodeficiency-like virus.
AB  - The development and persistence of virus-specific antibodies were investigated in
      eight cattle experimentally infected with the R29 isolate of bovine
      immunodeficiency-like virus (BIV). By 4 weeks postinoculation (p.i.), antibodies
      reactive to BIV gag- and env-encoded recombinant fusion proteins were detectable
      by immunoblotting in all animals. By 40 weeks p.i., seven of eight cattle had
      dramatically decreased Gag-specific antibodies, and anti-Gag reactivity remained
      very low or undetectable through 190 weeks p.i. Immunoprecipitation experiments
      revealed a similar loss of reactivity to nondenatured BIV Gag in these animals.
      In contrast, antibodies to a recombinant BIV Env protein were readily detectable
      throughout the study in all eight cattle. During the period of declining Gag
      antibody, infectious virus was recoverable from peripheral blood mononuclear
      cells of each animal. However, there was no evidence for sufficient amounts of
      BIV p26-containing immune complexes to explain the loss of anti-Gag reactivity.
      Interestingly, the single animal that maintained detectable anti-Gag reactivity
      throughout the study was repeatedly negative for virus recovery beyond 17 weeks
      p.i. All animals have remained clinically normal for over 4 years p.i., with no
      evidence of consistent changes in mononuclear cell subsets. These findings
      provide evidence that in BIV infection an early decline in Gag-specific antibody
      reactivity can occur without evidence of increasing viral replication or
      progression to overt clinical disease.

PMID- 8546803
TI  - The three C-terminal residues of human respiratory syncytial virus G glycoprotein
      (Long strain) are essential for integrity of multiple epitopes distinguishable by
      antiidiotypic antibodies.
AB  - Recently isolated escape mutants of human respiratory syncytial virus (HRSV) are
      described. The mutants were selected after serial passage of the Long strain in
      the presence of monoclonal antibodies directed against the attachment (G)
      glycoprotein. The genetic changes associated to the mutant phenotype were
      nucleotide substitutions leading to either amino acid replacements or new stop
      codons that shorten the G polypeptide by one amino acid. Sequence changes within
      the three C-terminal residues of the G molecule abolished multiple epitopes, some
      of them being distinguished only by virus-binding inhibition of the corresponding
      antibodies with a panel of antiidiotypic antisera. These results extend previous
      studies that demonstrated the extreme capacity of HRSV to accommodate multiple
      sequence changes within the antigenically relevant G protein C-terminal third.
      These results are discussed in terms of both the antigenic structure of the G
      molecule and the generation of new antigenic variants that mimic natural variants
      of HRSV.

PMID- 8546805
TI  - Approaches to alcohol control policy.

PMID- 8546804
TI  - Neutralization enzyme-linked immunosorbent assay for evaluation of immunity to
      measles virus.
AB  - A neutralization enzyme-linked immunosorbent (Nt-ELISA) assay for determination
      of protective immunity to measles virus was developed and evaluated. This
      procedure uses the same initial steps as performed to determine antibody titers
      by seroneutralization (Nt) test. However, a reduction in virus infectivity by
      neutralizing antibody was determined by quantitation of viral antigen using
      ELISA. The serum dilution that resulted in neutralization of 50% of infectious
      virus could be determined from the absorbance values. To be able to screen a
      large number of specimens, the conditions of the Nt-ELISA test were adjusted such
      that negative sera for measles antibodies and the positive ones were clearly
      distinguished on the basis of a single dilution (1:4). This test showed similar
      sensitivity (88.3%) and equal specificity as the Nt test when screening 136 serum
      samples from normal subjects. The estimation of protective antibody titers by Nt
      and Nt-ELISA methods was strongly correlated (correlation coefficient = 0.91).
      Thus, the measles Nt-ELISA test is rapid, reproducible, sensitive, and specific
      for detection of protective measles antibodies.

PMID- 8546806
TI  - The economics of alcohol policy.

PMID- 8546807
TI  - Community and municipal action on alcohol.

PMID- 8546808
TI  - Treatment approaches to alcohol problems.

PMID- 8546809
TI  - Two differing precursor genes for the salmon-type gonadotropin-releasing hormone
      exist in salmonids.
AB  - Salmon gonadotropin-releasing hormone (sGnRH) is considered to have an important
      role in the control of reproduction in salmonid fish. As a basis for
      understanding the physiological functioning of sGnRH at the molecular level, we
      characterized the nucleotide sequences of two types of cDNAs encoding the
      precursors of sGnRH in sockeye salmon (ss), Oncorhynchus nerka, by a cloning
      strategy based on reverse transcription-PCR. The two types of cDNAs are referred
      to as ss-pro-sGnRH-I and -II, and consisted of 435 and 481 bases respectively.
      Both precursors are predicted to contain a signal peptide, the hormone and a GnRH
      associated peptide that is attached to the hormone via a Gly-Lys-Arg sequence.
      The presence of two types of mRNAs hybridizing with either cDNA was confirmed by
      Northern blot analysis of brain RNA from sockeye salmon, masu salmon, O. masou,
      and rainbow trout, O. mykiss. The ss-pro-sGnRH-I cDNA had 97.2% and 82.8% overall
      identity with sGnRH cDNA from masu salmon and putative sGnRH cDNA deduced from
      the gene of the Atlantic salmon, Salmo salar respectively, whereas the ss-pro
      sGnRH-II cDNA had 80.0% and 91.2% overall identity with the former and the latter
      respectively. The nucleotide sequences of ss-sGnRH-I and -II cDNAs showed less
      similarity (79.3%). These results indicated that each salmonid species possesses
      two differing sGnRH genes. The results of Southern blot analysis using genomic
      DNA extracted from individuals support this evidence in sockeye salmon, masu
      salmon and rainbow trout.

PMID- 8546810
TI  - Semi-quantitative analysis of interleukin-1 alpha, interleukin-6 and interleukin
      8 mRNA expression by human thyrocytes.
AB  - It has been suggested that the thyroid itself may contribute to the inflammatory
      process observed in autoimmune thyroiditis by releasing the cytokines interleukin
      1 alpha (IL-1 alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), but studies
      of cytokine gene expression in thyrocytes have been limited and conflicting. A
      semi-quantitative reverse transcription-PCR technique has been used to
      investigate the expression of IL-1 alpha, IL-6 and IL-8 mRNA in the human thyroid
      cell line HTori3 and in cultures of primary human thyroid follicular cells
      (TFCs). Cytokine mRNA levels were examined over a 24-h period, and the modulatory
      effects of exogenous IL-1 alpha, interferon-gamma (IFN-gamma) and TSH
      investigated. Basal expression of IL-1 alpha, IL-6 and IL-8 mRNA was detected in
      HTori3 and primary TFC cultures. Stimulation with IL-1 (10 U/ml) for 12 h
      produced an increase in the level of IL-1 alpha mRNA in both primary TFC and
      HTori3 cultures. IL-6 and IL-8 mRNA levels were increased by the addition of IL-1
      in both cell types, and this effect was detected throughout the 24-h time-course.
      IFN-gamma (100 U/ml) had no significant effect on cytokine gene expression. A
      higher concentration of IFN-gamma (500 U/ml) had no significant effect on the
      expression of IL-1 alpha or IL-8 but produced an increase in the level of IL-6
      mRNA in primary cultures and in HTori3 cells. Addition of TSH (1 mU/ml) produced
      an increase in the level of IL-1 alpha mRNA in primary TFC and HTori3 cells, at
      12 and 24 h. TSH had no significant effect on the expression of IL-6 or IL-8
      mRNA. These results demonstrate that human TFCs constitutively express IL-1
      alpha, IL-6 and IL-8 mRNA and that this expression can be modulated by IL-1, IFN
      gamma and TSH.

PMID- 8546811
TI  - Molecular cloning and sequence analysis of striped bass (Morone saxatilis)
      gonadotrophin-I and -II subunits.
AB  - Two types of cDNA, each encoding a different beta-subunit of striped bass (Morone
      saxatilis, Teleostei) gonadotrophins (GTH-I beta and GTH-II beta), as well as the
      glycoprotein alpha-subunit, were cloned by screening a striped bass pituitary
      cDNA library. The probes used for screening the library were cloned cDNA
      fragments, generated by PCR amplification of reverse-transcribed mRNA obtained
      from two pituitaries. The nucleotide sequences of the alpha-subunit, GTH-I beta
      and GTH-II beta are 626, 524 and 580 bases long, encoding peptides of 117, 120
      and 147 amino acids respectively. Striped bass GTH-I beta and GTH-II beta share a
      sequence identity of 48% at the nucleic acid level, and 30% at the amino acid
      level. A cluster analysis of vertebrate pituitary glycoprotein beta-subunits
      suggests that teleost GTH-II beta is more closely related to tetrapod LH than to
      FSH. Administration of gonadotrophin-releasing hormone analogue ([D-Ala6,Pro9Net]
      LHRH) to juvenile striped resulted in ten-, two- and fivefold increases in the
      expression of the alpha-subunit, GTH-I beta and GTH-II beta respectively. These
      results suggest that each of the GTH subunits is differentially regulated, and
      further corroborate the functional duality of teleost gonadotrophins.

PMID- 8546812
TI  - Characterization of an estrogen-responsive element implicated in regulation of
      the rainbow trout estrogen receptor gene.
AB  - We previously reported that the expression of the rainbow trout estrogen receptor
      (rtER) gene is markedly increased by estradiol (E2). In this paper, we have used
      transient transfection assays with reporter plasmids expressing chloramphenicol
      acetyl transferase (CAT), linked to 5' flanking regions of the rtER gene
      promoter, to identify cis-elements responsible for E2 inducibility. Deletion
      analysis localized an estrogen-responsive element (ERE), at position +242, with
      one mutation on the first base compared with the consensus sequence. This element
      confers estrogen responsiveness to CAT reporter linked to both the herpes simplex
      virus thymidine kinase promoter and the homologous rtER promoter. Moreover, using
      a 0.2 kb fragment of the rtER promoter encompassing the ERE and the rtER DNA
      binding domain obtained from a bacterial expression system, DNase I footprinting
      experiments demonstrated a specific protection covering 20 bp (+240/+260)
      containing the ERE sequence. Based on these studies, we believe that this ERE
      sequence, identified in the rtER gene promoter, may be a major cis-acting element
      involved in the regulation of the gene by estrogen.

PMID- 8546813
TI  - Cloning and characterization of a chick embryo cDNA and gene for IGF-binding
      protein-2.
AB  - We have isolated and characterized a cDNA for IGF-binding protein-2 (IGFBP-2) and
      its gene from the chick embryo. Using primers from a conserved region of the
      mammalian IGFBP-2 sequence, a cDNA clone (1.6 kb) was isolated from an embryonic
      day-18 chick retina cDNA library. Although the clone was truncated at the 5' end,
      the complete coding sequence was obtained from 5' rapid amplification of cDNA
      ends and genomic sequencing. The open reading frame encoded a 311 amino acid
      precursor protein which contains a putative 36 residue signal peptide. The mature
      275 amino acid protein had a predicted M(r) of 33,500 and exhibited 71, 68, 68
      and 66% identity to rat, bovine, ovine and human IGFBP-2 cDNA respectively, with
      conservation of all 18 cysteines. The cDNA contained an RGD peptide but lacked a
      putative ATP-binding motif. A single transcript of approximately 2.3 kb was
      present in embryonic day-15 eye, brain, skeletal muscle, heart and intestine, but
      was virtually absent from embryonic day-15 liver. The chicken IGFBP-2 gene
      spanned approximately 38 kb, consisted of four exons, and was similarly organized
      to that of the rat and human. Southern blot analysis of chicken genomic DNA
      suggested that it is encoded by a single gene. The sequence information from the
      avian IGFBP-2 should be of value in examining the role of IGFBP-2 in vertebrate
      development.

PMID- 8546814
TI  - Calcium-activated proteases in the bovine parathyroid gland: potential role in
      degradation of parathyroid hormone to peptide fragments.
AB  - Our studies suggest that protein kinase C is involved in low calcium (Ca2+)
      stimulated secretion of parathyroid hormone (PTH) but not directly in high Ca(2+)
      stimulated intracellular degradation of PTH to secreted carboxyl-terminal
      fragments (C-PTH), an important component of Ca(2+)-regulated PTH secretion. The
      present study was undertaken to determine the presence of calcium-activated
      proteases, 84 kDa (micro)-calpain and 80 kDa (milli)-calpain, in the bovine
      parathyroid, and whether they could degrade PTH to C-terminal fragments.
      Immunocytochemistry of bovine parathyroid tissue using antibodies raised against
      bovine heart micro- and milli-calpain detected both isoforms of calpain. Western
      blotting of total bovine parathyroid cell protein prepared from primary cell
      cultures confirmed the presence of both isoforms of calpain, demonstrated by
      specific milli- and micro-calpain bands. Purified bovine PTH (bPTH) was incubated
      in vitro with human erythrocyte micro-calpain and the cleavage products were
      separated by reverse-phase HPLC. Eluant fractions were assayed with an RIA with
      equimolar sensitivity to C-PTH and bPTH, and peak areas integrated. Micro-calpain
      produced a C-PTH peak from bPTH which co-eluted with the major C-PTH secreted by
      parathyroid cells in culture. C-PTH production by micro-calpain, expressed as per
      cent area under the curve, increased from 0% in the absence of either micro
      calpain or Ca2+, to 71.5% when a 5:1 molar ratio of bPTH to calpain was used.
      Amino acid sequencing and analysis of the immunoreactive PTH cleavage products
      indicated the presence of two fragments of bPTH in the C-PTH peak, bPTH47-48 and
      bPTH69-84. In summary, both isoforms of calpain are present in the bovine
      parathyroid and calpains may play a role in the Ca(2+)-dependent degradation of
      PTH to secreted C-terminal fragments.

PMID- 8546815
TI  - Transcriptional down-regulation by epidermal growth factor of TRH receptor mRNA
      in rat pituitary cells.
AB  - To gain insight into the mechanism underlying the epidermal growth factor (EGF)
      induced changes in responsiveness to TRH and in the numbers of TRH receptors (TRH
      Rs) in the pituitary, we investigated the transcriptional regulation by EGF of
      the TRH-R gene in GH4C1 cells. Northern blot analyses and binding studies
      revealed that EGF reduced both TRH binding and TRH-R mRNA levels in a dose- and
      time-dependent manner, while no significant changes were observed in beta-actin
      mRNA levels. Addition of actinomycin D caused an acute increase in the basal TRH
      R mRNA level, and the rate of decrease of the TRH-R mRNA was identical in control
      and EGF-treated groups, suggesting that the stability of the TRH-R mRNA was not
      significantly affected in EGF-treated cells. Incubation with cycloheximide also
      induced an increase in the basal TRH-R mRNA level and completely reversed the EGF
      induced reduction of TRH-R mRNA levels. Furthermore, a nuclear run-on assay
      demonstrated that the rate of transcription of the TRH-R gene was significantly
      inhibited in cells treated with EGF. We conclude that (1) EGF decreases the
      expression of the TRH-R mRNA largely by reducing its rate of transcription, and
      this action requires the synthesis of new proteins, and (2) inhibitors of protein
      and RNA synthesis cause a significant increase in the basal TRH-R mRNA level,
      suggesting that there may be a short-lived protein suppressing the TRH-R mRNA
      level in the pituitary.

PMID- 8546816
TI  - Evidence for alternative splicing of the chicken vasoactive intestinal
      polypeptide gene transcript.
AB  - Two forms of chicken vasoactive intestinal polypeptide (VIP) mRNA have been
      identified by reverse transcription (RT)-PCR and RNase protection assay. The
      shorter form of chicken VIP mRNA encodes a protein that does not contain an
      analogue of rat peptide histidine isoleucine (PHI) 1-27 or human peptide
      histidine methionine 1-27. The larger form encodes both VIP and a chicken
      analogue of PHI 1-27 in the same protein product. Three VIP cDNAs isolated from a
      chicken hypothalamic cDNA library were derived from the shorter mRNA. Sequence
      analysis of the longest clone identified an open reading frame that codes for a
      165 amino acid preproVIP protein and contains two polyadenylation signals. In
      situ hybridisation with an oligonucleotide probe from the VIP cDNA sequence
      showed that VIP-encoding mRNA occurs in cells in the basal hypothalamus, an area
      of the brain known to contain VIP neurosecretory neurones. RT-PCR of total RNA
      from liver, kidney, gut, pancreas, pituitary, cerebellum, forebrain and
      hypothalamus, using primers derived from the VIP cDNA sequence, showed that the
      shorter form of VIP mRNA is present in all of these tissues. The sequence of the
      longer form of VIP mRNA was obtained by sequencing a portion of the VIP gene from
      genomic DNA. This revealed a potential exon that was not represented in the VIP
      cDNA clones analysed. RT-PCR with primers from this sequence showed that it was
      expressed in the gut and hypothalamus. RNase protection assays confirmed the
      presence of the two forms of mRNA in gut and hypothalamus. The relative
      proportions of the two mRNA forms were: 97.8% VIP only, 2.2% PHI/VIP in the
      hypothalamus and 98.5% VIP only, 1.5% PHI/VIP in the gut. In conclusion, chicken
      VIP mRNA is alternatively spliced. The shortest form, which encodes a
      preproprotein containing only the VIP peptide, is the most abundant. The longer
      form of chicken VIP mRNA encodes a preproprotein containing sequences for both
      VIP and a chicken form of PHI.

PMID- 8546817
TI  - Transcriptional regulation of Na/K-ATPase by corticosteroids, glycyrrhetinic acid
      and second messenger pathways in rat kidney epithelial cells.
AB  - Corticosteroid regulation of Na/K-ATPase is of key importance in the modulation
      of Na+ transport across renal tubular epithelia. In amphibian renal cells,
      aldosterone induction of Na/K-ATPase alpha 1 and beta 1 subunit gene
      transcription is mediated by an indirect mechanism dependent on the synthesis of
      a labile protein. In mammalian target cells, while both mineralo- and
      glucocorticoids increase the levels of Na/K-ATPase alpha 1 and beta 1 subunit
      mRNA and enzyme activity, they are diminished by glycyrrhetinic acid (GE), the
      active ingredient of licorice. To investigate the mechanisms underlying the
      regulation of mammalian renal Na/K-ATPase, levels of alpha 1 and beta 1 mRNA were
      measured in rat kidney epithelial (NRK-52E) cells treated with a range of
      concentrations of aldosterone, corticosterone and GE in the presence of a
      specific inhibitor of mRNA synthesis, dichlororibofuranosylbenzimidazole (DRB),
      an inhibitor of total RNA synthesis, actinomycin D (ActD), and the protein
      synthesis inhibitor cycloheximide (CHX). In addition, GE was co-incubated with
      the sodium channel antagonist benzamiloride (BZ). The increase in both alpha 1
      and beta 1 mRNA levels following aldosterone and corticosterone was completely
      abolished by treatment with ActD and DRB, while CHX did not affect this response.
      Similarly, the GE-induced decrease in alpha 1 and beta 1 mRNA was also completely
      abolished by ActD and DRB, but not by CHX or by BZ. The half-lives of alpha 1 and
      beta 1 mRNA in these cells (means +/- S.E.M., n = 4), estimated from the rate of
      mRNA decay in the presence of DRB, were 6.8 +/- 0.3 and 4.8 +/- 0.2 h
      respectively. This was unaffected by GE. The inhibitory action of GE on alpha 1
      and beta 1 mRNA levels was accompanied by a dose-dependent decrease in levels of
      intracellular cAMP (means +/- S.E.M., n = 4) from 395 +/- 28 fmol cAMP/microgram
      total cell protein to between 275 +/- 19 fmol/micrograms total cell protein (0.1
      microM GE) and 78 +/- 11 fmol/micrograms total cell protein (10 microM GE). This
      was abolished following down-regulation of protein kinase C by prolonged
      treatment with the phorbol ester tetradecanoylphorbol-13-acetate (TPA), and by
      pertussis toxin (PT), but not by cholera toxin (CT). Indeed, subunit mRNA levels
      were increased by 8-bromo-cAMP (2.2-fold) and stimulators of adenylate cyclase
      activity, i.e. forskolin (2.1-fold), PT (2.1-fold) and CT (1.9-fold), but not by
      TPA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8546818
TI  - Burning the largest immune organ.

PMID- 8546819
TI  - Essential concepts of inflammation and immunity.
AB  - Virtually all patients in acute or critical care settings experience some degree
      of immune system alteration, which places them at risk for serious potential
      complications, including sepsis and debilitation. Nurses need a good working
      knowledge of specific areas of immune function to provide a safe environment,
      adequate patient support, and appropriate early interventions to prevent
      complications. This article presents information about basic immune function and
      current and potential uses for new immunodulating agents, such as granulocyte
      macrophage--colony-stimulating factor.

PMID- 8546820
TI  - Hand washing: a ritual revisited.
AB  - This article summarizes a critical analysis of 18 studies that examined the link
      between hand washing and infection. Although several factors made it difficult to
      evaluate the effect of hand washing, the authors conclude that (1) hand washing
      can add incremental value to infection-control strategies in acute care settings,
      (2) patient hand hygiene may influence infection rates, and (3) the effect of
      "ideal" hand washing on nosocomial infection rates is unlikely to be
      quantifiable.

PMID- 8546821
TI  - Wound infection following trauma and burn injuries.
AB  - Wounds that result from trauma and burn injuries may lead to the development of
      infection from the mechanism of injury, bacterial contamination, exogenous and
      endogenous sources, and impaired host defenses. Knowledge of these factors,
      combined with thorough wound assessment, differentiation between contaminated and
      infected wounds, the appropriate use of wound cultures and antibiotics, and the
      appropriate selection of wound-management techniques, is important in the
      optimization of wound healing.

PMID- 8546822
TI  - Patterns of infection in the solid-organ transplant recipient.
AB  - Infection continues to be a major complication after transplantation. This
      article addresses common postoperative infections and how a complete preoperative
      and postoperative assessment of infections can affect the patient's morbidity and
      mortality. Prevention and treatment regimens for common infections that affect
      the immunosuppressed patient population also are discussed.

PMID- 8546823
TI  - HIV infection/AIDS and critical care.
AB  - The complications of HIV infection may involve almost any organ system, often
      resulting in severe dysfunction that may be life threatening. Other disorders not
      associated with HIV infection may occur in HIV-infected patients and may be
      severe enough to require critical care. The risk for HIV infection may be
      unrecognized or undiagnosed at the time of admission to the intensive care unit,
      placing nurses and other health care providers at risk for the transmission of
      disease. In the critical care setting, compliance with infection control requires
      the integration of specific policies and procedures into crises-based practices.

PMID- 8546824
TI  - Critical care and tuberculosis.
AB  - The scientific literature documents the resurgence of airborne nosocomial
      transmission of Mycobacterium tuberculosis to patients and health care providers
      that has occurred in the last decade. Tuberculosis may not be recognized or
      diagnosed at the time of admission to the intensive care unit, adding to the risk
      of disease transmission to nurses, other health care providers, and patients. In
      the critical care setting, compliance with infection control requires the
      integration of specific policies and procedures into crises-based practices.

PMID- 8546825
TI  - Antibiotic prophylaxis in the critical care setting.
AB  - The prevention of infection in critically ill patients is a difficult and often
      frustrating task. Selective digestive decontamination may be a useful means of
      preventing infections in specific patient populations; however, not all critical
      care patients will benefit. In this article, mechanisms of antimicrobial
      resistance are discussed along with the consideration of specific measures to
      deal with this growing dilemma. Concerns about specific microorganisms, such as
      vancomycin-resistant enterococcus and multidrug-resistant Enterobacter species,
      are addressed. It is clear that the use of antimicrobial agents is not the only
      solution to the problem of infection in critically ill patients.

PMID- 8546826
TI  - Intravascular medication delivery devices and monitoring systems.
AB  - This article presents a review of the current standards and the research of
      infection-control practice for medication delivery devices and monitoring
      equipment. The standards of the Centers for Disease Control and Prevention,
      Intravenous Nursing Society, and the Association for Professionals in Infection
      Control and Epidemiology, Incorporated, are reviewed and compared to the current
      research.

PMID- 8546827
TI  - Device-related, nonintravascular infections.
AB  - The intensive care environment is conducive to the transmission of microorganisms
      because of the array of medical equipment and the frequent contamination of the
      hands of health care workers. This article reviews recommended nursing
      interventions for the following nonintravascular devices: automatic implantable
      cardioverter defibrillators, chest tubes, peritoneal dialysis, enteral nutrition,
      electronic thermometers, oximeter sensors, and urinary drainage devices.

PMID- 8546828
TI  - Critical care-acquired pneumonia.
AB  - Nosocomial infections are the second most common hospital-acquired infections.
      The Centers for Disease Control and Prevention recently published an updated
      Guidelines for the Prevention of Nosocomial Pneumonia. A summary of these
      recommendations and general preventive strategies are presented in this article.

PMID- 8546829
TI  - Management constraints in infection control.
AB  - Critical care patients are at risk for developing endogenous and exogenous
      nosocomial infections. Essential components of an infection-control program in
      the critical care environment are the structural design of the critical care unit
      and the surveillance, prevention, and control of infection functions. Management
      strategies include employee infection control and education. Knowledge and
      education are the most important management tools in the control of infection in
      the critical care environment.

PMID- 8546830
TI  - Understanding parameters of risk and risk measurement in critical care.
AB  - Scientifically valid data about the risks and rates of nosocomial infection are
      important to assist critical care nurses in developing clinical care improvement
      strategies. Contemporary epidemiologic methods should be used to facilitate the
      accurate assessment of data, whether for intrahospital or interhospital
      comparisons. Results of infection monitoring should be integrated into unit-based
      quality improvement efforts, practice decisions, and nursing education systems.

PMID- 8546831
TI  - Practical application of sharing surveillance data.
AB  - This article provides several practical and effective mechanisms for reporting
      meaningful information on nosocomial infections to critical care and other
      specific units. Roadblocks and a small sample of hospital practices for reporting
      unit-specific infections are described. Graphic presentations, especially line
      stay histograms, are recommended.

PMID- 8546832
TI  - Health policy for infection control and epidemiology in critical care.
AB  - Intensive care medicine is a relatively new medical specialty that was instituted
      in the wake of massive polio epidemics in the early 1950s. This article presents
      various government and accrediting agencies and professional organizations that
      contribute to infection-control efforts in critical care medicine. Collaboration
      among clinicians and their respective professional organizations is required to
      ensure effective hospital infection control.

PMID- 8546833
TI  - Reducing risks through quality improvement, infection control, and risk
      management.
AB  - Health care organizations in America are undergoing major changes. As these
      changes are occurring, organizations are being asked to demonstrate how they
      monitor and improve their services to provide cost-effective, quality care. The
      integration of quality improvement methodologies, risk management programs, and
      infection-control systems provides the structure necessary for identifying
      organization risks and attempting to eliminate them. This integration is
      demonstrated by a case study for reducing needlestick injuries in the intensive
      care unit.

PMID- 8546834
TI  - Media mania: hot infections.
AB  - Television, radio, and the print media increasingly are reporting information of
      a medical nature, sharing the latest research findings. Disease-related articles
      are a staple of the weekly news magazines and tabloids. To keep current, nurses
      must evaluate everything they are exposed to and should read and listen with
      educated eyes and ears.

PMID- 8546835
TI  - Optimization of rice alpha-amylase production using temperature-sensitive mutants
      of Saccharomyces cerevisiae for the PHO regulatory system.
AB  - A typical example of rational system synthesis for bioproduction by the
      cultivation of microorganisms harboring a recombinant plasmid was studied. First,
      two temperature-controllable expression systems for a foreign gene in
      Saccharomyces cerevisiae were constructed. The promoter of the PHO84 gene, which
      encodes an inorganic phosphate (Pi) transporter of S. cerevisiae and is
      controlled by Pi concentration through the PHO regulatory system, was used. And
      two temperature-sensitive mutants of S. cerevisiae for the PHO regulatory system
      were used as the host with rice alpha-amylase expression vector. One was
      temperature-sensitive pho81 mutant, SH3337, and the other was temperature
      sensitive pho80 mutant, YKU107. When the strain SH3337 is cultivated at a lower
      temperature, the rice alpha-amylase gene connected downstream of the PHO84
      promoter is expressed, but at a higher temperature, it is not. Conversely, with
      the strain YKU107, the transcription of the rice alpha-amylase gene is induced at
      a higher temperature and repressed at a lower one. The optimal cultivation
      temperature strategies for maximum production of rice alpha-amylase in batch
      cultures of these two recombinant strains were then determined by the Maximum
      Principle using the relationships of the specific growth and specific production
      rates to the cultivation temperature. The optimal strategies were easy to realize
      and were shown to be effective for maximum product. Finally, under these maximum
      alpha-amylase production strategies, the alpha-amylase activities and alpha
      amylase yields in terms of glucose consumption for these recombinant strains were
      calculated on the basis of experimental data and compared for various operation
      times. The study demonstrates how a foreign gene expression system can be
      synthesized using a temperature-sensitive mutant with a given objective and under
      given constraints.

PMID- 8546836
TI  - Cell growth and monoclonal antibody production in the presence of antigen and
      serum.
AB  - The impact that the continuous presence in the fermentation broth of the cognate
      antigen has on the serum-supplemented hybridoma cell cultures was investigated.
      Both soluble and immobilized antigen at various concentrations was applied. The
      cell line (ATCC TIB191) was cultured in a serum-supplemented PFHM-II medium in T
      flasks. Sepharose gel beads provided the immobilization matrix, and bovine gamma
      globulin was the carrier protein upon which the antigen, picric acid, was
      conjugated. Produced antibody, after elution from the beads by displacement with
      free picric acid, was measured with an ELISA. Soluble antigen--carrier protein
      conjugates showed no effect on the cultures, but the immobilized antigen had a
      strong influence on them. Cell growth rate and total antibody production
      decreased as the amount of immobilized antigen increased from 16:10 (units are in
      (mol of Ag/mol of carrier):(mg of carrier/mL of beads) to 36:40. Most
      importantly, the specific antibody production rate switched from growth phase
      independent behavior in the antigen-free cultures to growth phase-dependent
      behavior in the immobilized antigen cultures. Furthermore, during the early
      stationary phase of the cultures with immobilized antigen, the specific antibody
      production was 20-100% higher relative to the production rate in antigen-free
      cultures. This increased specific antibody production rate would be particularly
      useful in increasing the volumetric productivity of perfusion-type bioreactors
      for hybridoma cell cultures.

PMID- 8546837
TI  - Improved homogenization of recombinant Escherichia coli following pretreatment
      with guanidine hydrochloride.
AB  - Pretreatment of recombinant Escherichia coli, expressing human growth hormone
      inclusion bodies, with guanidine hydrochloride and Triton X-100 prior to high
      pressure homogenization has been investigated. Homogenates were analyzed for
      protein release, viscosity, and particle size. We were able to reduce the number
      of passes required for cell disruption and the number of downstream processing
      steps required for the recovery of protein from inclusion bodies by pretreating
      cells with guanidine HCl and Triton X-100. Pretreatment of exponential growth
      phase cells with 1.5 M guanidine HCl and 1.5% Triton X-100 gave adequate
      disruption after one pass at 41 MPa with a particle size distribution similar to
      that for untreated cells disrupted after one pass at 62 MPa. This combination of
      guanidine HCl and Triton X-100 was also selected so as to wash the inclusion
      bodies without solubilization of the human growth hormone. Pretreatment of cells
      with 4 M guanidine HCl produced cell debris that was substantially smaller than
      the debris from untreated cells and partially solubilized the inclusion bodies.
      Cells harvested in the stationary growth phase were more resistant to high
      pressure homogenization and pretreatment.

PMID- 8546838
TI  - Mathematical model for analysis of mass transfer for immobilized cells in lactic
      acid fermentation.
AB  - A new mathematical model is proposed to analyze the mass transfer behavior in
      lactic acid fermentation using immobilized cells entrapped in calcium alginate.
      The model is comprised of material balance equations for glucose, free lactic
      acid, and several ions. The dissociation rate of lactic acid (rdiss) is involved
      in the proposed equations. To solve the equations numerically, a modified
      calculating method is proposed. Through model analysis, the possible mass
      transfer behavior in the gel bead was discussed. The model is validated by
      comparisons with the experimental results obtained from batch and continuous
      fermentation. The simulations using the model were made to investigate the mass
      transfer limitation in the gel beads. The results showed that the cell density
      gradient was formed in the gel beads and it was caused by the accumulation of the
      inhibitory product (free lactic acid), not by substrate starvation. Moreover,
      unusual mass transfer behavior of lactate ion in the immobilization support was
      pointed out.

PMID- 8546839
TI  - Alteration of hybridoma viability and antibody secretion in transfectomas with
      inducible overexpression of protein disulfide isomerase.
AB  - Monoclonal antibody (mAb)-secreting transfectomas with dexamethasone inducible
      expression of the mammalian endoplasmic reticulum foldase and chaperone protein
      disulfide isomerase (PDI, ERp59) were generated from the murine 9.2.27 hybridoma
      in order to obtain in vivo evidence of whether alteration of the level of PDI,
      believed to be involved in immunoglobulin (Ig) assembly, results in alteration of
      mAb secretion kinetics. Using an RNase refolding assay, the specific activity of
      endogenous PDI in the 9.2.27 hybridoma was found to be constant during batch
      growth. An expression vector for glucocorticoid-inducible overexpression of PDI,
      pMMTVPDI, was constructed from pMAMneo using a rat PDI cDNA. Cell lysates of
      stable transfectomas contained 2-4-fold higher levels of PDI mRNA and increased
      levels of PDI protein, detected by immunoblotting, following induction with 0.1
      microM dexamethasone. Monoclonal antibody secretion kinetics were evaluated in
      12.5 mL shake flasks, a 100 mL spinner, and a 1 L aerated batch reactor. A
      transfectoma was found with altered mAb secretion kinetics during cell growth
      following dexamethasone induction of PDI overexpression. Specific mAb secretion
      rate was not significantly increased following dexamethasone induction; however,
      hybridoma viability was sustained longer during the stationary phase of cell
      growth and hence total antibody yield was increased in comparison to the parent
      9.2.27 hybridoma.

PMID- 8546840
TI  - Effect of viscosity upon hydrodynamically controlled natural aggregates of animal
      cells grown in stirred vessels.
AB  - The effect of medium viscosity upon cell growth and aggregate characteristics of
      baby hamster kidney (BHK) cells cultivated in stirred tanks was evaluated. Two
      thickening agents were tested, 9300 MW dextran and a low-viscosity sodium
      (carboxymethyl)-cellulose; both were used in two different sets of experiments:
      (i) 250 cm3 Wheaton spinner flasks with a ball impeller operated at 45 rpm; (ii)
      500 cm3 Corning spinner flasks with a paddle impeller, operated at constant power
      dissipation (88 cm2 s-3). Aggregate diameter and the fraction of cells in
      aggregates increased with the increase in viscosity. Power laws were applied to
      the experimental results. A dependence of aggregate size upon power dissipation
      of the order of -0.19 and kinematic viscosity of 0.34 and 0.49 for the constant
      agitation and constant power dissipation tests were obtained, respectively. A
      model based upon the entire universal-equilibrium range (i.e., the entire
      spectrum of isotropic eddies) was used to predict theoretical relationships
      between the variables studied. The model leads to a power dependence of -0.25 for
      the energy dissipated in the entire universal-equilibrium range and between 0.25
      and 0.5 for the kinematic viscosity in the viscous dissipation subrange,
      depending on the energy correlation used; it also gives a good explanation for
      the dependence of aggregate size on the hydrodynamics of the vessel.

PMID- 8546841
TI  - Partial and total cell retention in a filtration-based homogeneous perfusion
      reactor.
AB  - Suspended mammalian cells can be cultivated in a variety of operational modes
      (pure chemostat, total cell retention, or partial cell retention) in a
      homogeneous perfusion bioreactor by varying the cell bleed rate. Hybridomas were
      grown in the reactor at a perfusion rate of 2.0 day-1 for over 10 weeks at
      different specific growth rates and viable cell densities achieved by varying the
      extent of cell retention. Cell metabolism in the reactor was found to vary with
      the extent of cell retention, which determined both cell density and specific
      growth rate. With partial cell retention, the nutrient consumption and metabolite
      production rates decreased with both increasing growth rate and increasing cell
      density. The specific and volumetric antibody production rates, however,
      increased dramatically with cell density (and to a lesser extent with decreasing
      growth rate). The specific MAb production rate was lower with total cell
      retention than with partial retention at the same growth rate. Since the reactor
      can be operated over a range of perfusion rates and extents of cell retention,
      the system can be used to culture cell lines with widely different productivity
      patterns.

PMID- 8546842
TI  - Fluctuating shear stress effects on stress fiber architecture and energy
      metabolism of cultured renal cells.
AB  - The project investigates the relationship between the external shear force and
      the actin cytoskeleton along with the metabolic changes occurring inside the
      cells due to this force. Anchorage-dependent Madin Darby canine kidney (MDCK)
      cells were placed in spinner flasks with paddle-type stirrers agitated at 20 rpm,
      where they experienced shear stress fluctuations from 0.02 to 0.27 dyn/cm2 in
      magnitude. Following fixation, permeabilization, and staining with rhodamine
      phalloidin, the relative amounts and distribution of F-actin stress fibers in the
      1 micron basal layer of the cells were visualized by confocal microscopy. These
      structures disappeared after 12-15 h of exposure to shear stress. Previous
      results showed that the stress fibers disappear, leading to loss of epithelial
      attachment, after only 1 h of starvation-induced energy depletion. Therefore, in
      this study, the energy metabolism of the cells was established by measuring
      adenosine triphosphate (ATP) levels at different time intervals. No statistical
      difference in ATP content was found between the shear-stressed cells and the
      controls, showing that shear stresses cause cytoskeletal reorganization by a
      mechanism other than ATP depletion.

PMID- 8546843
TI  - The immunobiology and immunopathology of chlamydial infections.
AB  - Chlamydiae are obligate intracellular bacterial pathogens of eukaryotic cells
      responsible for a wide variety of important human and animal infections. In
      humans, chlamydial infections are generally localised to superficial epithelial
      or mucosal surfaces, are frequently asymptomatic and may persist for long periods
      of time if untreated, inducing little protective immunity. Nevertheless,
      neutralising antibodies of limited efficacy are produced against the main
      chlamydial outer envelope protein, while gamma interferon (IFN gamma) is
      chlamydiastatic and paradoxically may play a role both in chlamydial persistence
      and in protective immunity. Delayed hypersensitivity responses to chlamydiae
      caused by repeated or persistent infection are thought to be important in the
      development of the severe scarring sequelae characteristic of cicatricial
      trachoma and of chronic salpingitis. Chlamydial heat shock proteins bearing close
      homology with their human equivalents may be major targets for immunopathological
      responses and their expression is upregulated in IFN gamma induced persistent
      infection. C. pneumoniae, a common cause of acute respiratory infection in
      humans, may persist in coronary arteries and is strongly implicated as a risk
      factor in atherosclerosis and in acute myocardial infarction. This paper reviews
      the immunology and immunopathology of chlamydial infections in the context of the
      unique biology of this fascinating but challenging group of organisms.

PMID- 8546844
TI  - Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in soft tissue
      sarcoma. Is prognostic significance histotype-specific?
AB  - Abnormal patterns of proliferation characterize the behavior of many tumors.
      Proliferating cell nuclear antigen (PCNA) and Ki-67 are two cell cycle antigens
      which are expressed in proliferative states. Our study examines the prognostic
      value of these cell-cycle antigens in soft tissue sarcoma (STS). Paraffin
      embedded primary tumor tissues from 185 patients (1980-92) were stained with the
      anti-PCNA antibody PC-10; 182 of these were stained with the antibody MIB-1 for
      Ki-67. Using PCNA (< or = 50; > 50%) and Ki-67 (< or = 10; > 10%) indices, we
      examined and compared metastasis-free survival (MFS) in a mixed-histotype group,
      as well as after subdivision into MFH and non-MFH groups. Fifty-seven patients
      developed metastases. The median follow-up for survivors was 6 (2-13) years. In
      the mixed series, the 2-year MFS for a PCNA index < or = 50 was 76%, and for an
      index > 50 56%. Survival predicted by Ki-67 index was comparable. PCNA index (but
      not Ki-67) strongly correlated with the incidence of metastasis in MFH tumors and
      predicted 2-year MFS of 81 vs 48%. In contrast, Ki-67 index (but not PCNA)
      strongly correlated with metastasis in non-MFH tumors and predicted 2-year MFS
      survival of 90 vs 45%. No correlation existed between PCNA and Ki-67 indices in
      the mixed histotype, MFH or non-MFH groups. In combination, a high PCNA and Ki-67
      index correlated with poor survival, a high PCNA and lower Ki-67 index (or vice
      versa) with an intermediate survival, and low PCNA and Ki-67 indices with the
      best survival. The pattern of PCNA and Ki-67 expression raises the possibility of
      histotype specificity.

PMID- 8546845
TI  - Haemophilus influenzae release histamine and enhance histamine release from human
      bronchoalveolar cells. Examination of patients with chronic bronchitis and
      controls.
AB  - Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae)
      and Branhamella catarrhalis (B. catarrhalis) are often found in the lower
      respiratory tract of patients with chronic bronchitis. Earlier studies have shown
      that bacteria induce mediator release from human basophils and parenchymal lung
      mast cells. In this study the capability of bacteria to trigger or potentiate
      histamine release from superficially located mast cells in the airway epithelium
      was studied in cell suspensions obtained by bronchoalveolar lavage in patients
      with chronic bronchitis (CB). In approximately half of the patients H. influenzae
      and Staphylococcus aureus (S. aureus) were found to trigger histamine release,
      whereas no response was obtained by S. pneumoniae or B. catarrhalis. The mediator
      release was caused by a non-IgE-dependent mechanism. At lower concentrations of
      H. influenzae causing no histamine release the bacterium was found to enhance IgE
      mediated histamine release triggered by anti-IgE antibody. The synergy was more
      pronounced in patients with CB than in controls. Since H. influenzae is found in
      the lower respiratory tract of the patients but not in normal individuals, the
      infection here may via histamine release lead to harmful effects on the airways
      of importance for precipitation and exacerbation of chronic bronchitis.

PMID- 8546846
TI  - Nitric oxide regulates the chemiluminescence from stimulated human neutrophils.
AB  - Nitric oxide produced from L-arginine by a variety of cells, is a biologically
      active compound that can react with iron and thiols. The objective of this study
      was to investigate the effects of nitric oxide on the respiratory burst from
      human neutrophils. Treatment with nitroprusside increased the chemiluminescence
      from neutrophils stimulated with PMA or collagen, but not from cells stimulated
      with FMLP. Addition of L-arginine increased the chemiluminescence after
      stimulation with any of the three stimuli, while N omega-nitro-L-arginine methyl
      ester decreased it. Low doses of nitric oxide, either endogenously or exogenously
      produced, probably inhibited catalase or glutathione, leading to an increase in
      hydrogen peroxide available for chemiluminescence detection. This indicates that
      nitric oxide may reduce the protection against hydrogen peroxide in tissue and in
      invading catalase-positive bacteria.

PMID- 8546847
TI  - Inhibition of growth of Proteus mirabilis and Escherichia coli in urine in
      response to fasting and vegetarian diet.
AB  - It has recently been shown that serum antibody levels against Proteus mirabilis
      decreased in patients with rheumatoid arthritis who improved clinically during
      treatment with 7-10 days of fasting followed by a one-year vegetarian diet. As P.
      mirabilis is commonly implicated in urinary tract infections, this study was
      carried out to examine whether fasting and vegetarian diet may influence the
      growth of P. mirabilis and Escherichia coli in urine. Urine samples were
      collected from 22 patients who were referred to a health farm for various
      reasons. The dietary regimen recommended by the health farm consisted of fasting
      for 7 to 10 days followed by a vegan diet. The growth of both bacteria in urine
      samples collected after 8 days was significantly slower than in samples collected
      at baseline. In urine samples collected after 18 days growth was also reduced,
      although not significantly for E. coli. Our results show that dietary
      manipulation may reduce the ability of urine to support the growth of P.
      mirabilis and E. coli.

PMID- 8546849
TI  - Experimental and clinical research: future directions in neuropsychology in
      general and Brain and Cognition in particular.

PMID- 8546848
TI  - Glomerular antigens in severe hereditary nephrosis.
AB  - In search of the basic defect and cell type responsible for the massive treatment
      resistant proteinuria of congenital nephrotic syndrome of the Finnish type (CNF),
      we examined tissue samples of CNF kidneys using established antibody and lectin
      markers of various glomerular cell types. Markers of vascular endothelium
      (antibodies to factor VIII and a human homologue of podocalyxin (anti-PHM5) and
      UEA I lectin) showed no qualitative changes in the endothelial cells of glomeruli
      or peritubular areas in CNF as compared with controls. Markers of glomerular
      mesangial cells (antibodies to desmin, smooth muscle actin, RCA I lectin)
      revealed a secondary increase in mesangial reactivity reflecting the sclerosis
      and expansion of the mesangial areas in CNF. Markers of visceral epithelial cells
      (antibodies to a human homologue of podocalyxin, C3b receptor, vimentin, common
      lymphocytic leukemia antigen, gp44, and the WGA, LFA and, after neuraminidase
      treatment, PNA lectin) failed to show appreciable qualitative changes in CNF
      kidney samples. Interestingly, the alpha 2 beta 1 integrins appeared greatly
      reduced in all CNF samples studied, possibly explaining the mechanisms of CNF
      associated proteinuria.

PMID- 8546850
TI  - Dementia and parkinsonism: an emerging research area.

PMID- 8546852
TI  - Acetylcholine and hallucinations: disease-related compared to drug-induced
      alterations in human consciousness.
AB  - Newly proposed criteria for Lewy body dementia include alterations in
      consciousness. Lewy body dementia is also associated with a disturbance in
      cholinergic transmission; neocortical cholinergic deficits in this disorder are
      more extensive than in Alzheimer's disease and are correlated with symptoms
      commonly associated with delirium, such as visual hallucinations. The traditional
      view that derangements of the basal forebrain cholinergic system in Alzheimer's
      disease relate specifically to memory impairment is assessed in terms of a more
      general role for cortical acetylcholine in consciousness. This extends the
      concept that cortical acetylcholine enhances neuronal signal to noise ratio. It
      is suggested that muscarinic receptor activation in the cortex is involved in
      confining the contents of the discrete self-reported conscious "stream." In the
      absence of cortical acetylcholine, currently irrelevant intrinsic and sensory
      information, which is constantly processed in parallel at the subconscious level,
      enters conscious awareness. This is consistent with the ability of anti
      muscarinic drugs administered medically, recreationally, or ritualistically to
      induce visual hallucinations and other perceptual disturbances. The hypothesis is
      explored through comparisons between muscarinic and nicotinic receptor
      psychopharmacology and between the pathology of the basal forebrain as opposed to
      pedunculopontine cholinergic systems in different diseases of the human brain
      affecting consciousness and cognition. The paradoxical effects of muscarinic
      receptor blockade to induce hallucinations and of REM sleep-associated
      cholinergic activation of the thalamus to induce dreaming may be related to the
      differential distribution and activity of muscarinic receptor subtypes or to the
      differing responses of intrinsic GABA neurons in cortex and thalamus.

PMID- 8546851
TI  - Neuropsychiatric features of Lewy body disease.
AB  - Although traditionally associated with Parkinson's disease, the eosinophilic
      intracytoplasmic neuronal inclusion known as the Lewy body has recently been
      regarded as the primary neuropathologic finding in a variety of conditions
      affecting the aging brain. The term Lewy Body Disease (LBD) will be used in this
      review to refer to a spectrum of clinical states varying from those due to
      incidental or mildly symptomatic histopathologic changes to progressive dementia
      and psychosis. Many unanswered questions remain about the neurobehavioral and
      neuropathological implications of Lewy bodies, but it is useful to consider the
      LBD spectrum in terms of the variable effects on neuropsychiatric function that
      can be observed clinically.

PMID- 8546853
TI  - Genetic evidence that the Lewy body variant is indeed a phenotypic variant of
      Alzheimer's disease.
AB  - Lewy Body Variant (LBV) patients present as Alzheimer's disease (AD) clinically;
      about two-thirds also have mild extrapyramidal features. At autopsy, neocortical
      and brain stem Lewy bodies are present in addition to changes diagnostic of AD.
      We have found that the Apolipoprotein E4 allele is a major genetic risk factor
      for LBV as it is for "pure AD," in contrast to subjects with diffuse Lewy body
      disease or Parkinson's disease. This genetic evidence supports the concept that
      LBV--the second most common neurodegenerative form of dementia--is a phenotypic
      variant of AD.

PMID- 8546854
TI  - Lewy body diseases with dementia: pathophysiology and treatment.
AB  - There are four major Lewy body disorders with dementia: Parkinson's disease (PD),
      PD with Alzheimer's disease (AD), cortical Lewy bodies and neuritic plaques, and
      cortical Lewy bodies and no concomitant AD-type pathology. A variety of
      pathogenetic processes may underly this panoply of diseases including oxidative
      stress, excitatory amino acid toxicity, amyloidogenesis, neurofibrillary tangle
      formation, inflammation, apoptotic cell death, and neurotransmitter deficiency.
      Treatment strategies include transmitter replacement, neuroprotection, agents to
      limit AD-type pathology, iron chelation, and anti-inflammatory drugs. Patients
      with Lewy body disorders exhibit cognitive decline resulting from a variety of
      disease processes and treatment must address the disease-specific pathogenesis.

PMID- 8546855
TI  - The neuropsychology of Parkinson's disease.
AB  - This article discusses the neuropsychological profile of Parkinson's disease from
      the perspective of cognitive theory, anatomical organization, and unit recording
      data. Despite the point of origin, methodologically controlled studies are
      converging to support the position that patients with this disorder suffer
      selective impairment in the acquisition of novel tasks which rely on internal
      (subjective) processing for the efficient establishment of new cognitive
      "habits." The roles of attention and learning as well as of unit activity within
      the relevant networks are considered. Also included are recent but important
      concepts from personality theory which potentially enhance understanding of the
      neuropsychology of Parkinson's disease.

PMID- 8546856
TI  - The use of PET in Parkinson's disease.
AB  - Activation studies with positron emission tomography (PET) have provided an
      understanding of the pathophysiology of akinesia and tremor in Parkinson's
      disease (PD). [18F]6-fluoro-L-dopa (FD)-PET and dopamine receptor imaging by PET
      can assist in the differential diagnosis of various forms of parkinsonism. FED
      PET is capable of detecting subclinical dopaminergic deficits. This allows not
      only the early or preclinical detection of PD but also the investigation of
      subclinical lesions of the substantia nigra in PD-related disorders. Longitudinal
      studies of PD and MPTP induced parkinsonism have provided new insight into the
      pathogenesis of PD.

PMID- 8546857
TI  - Neuropsychological features of progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is the epitome of a subcortical dementia
      process. Due to its relative rarity, there is only a small literature on the
      neuropsychological consequences of PSP. The findings to date demonstrate that PSP
      patients have dramatically slowed information processing and motor execution,
      rapid forgetting, problems in orienting attentional resources, and difficulty in
      planning and shifting conceptual sets. The pattern and severity of these deficits
      are unique to PSP and suggest that the study of PSP patients can provide a
      special insight into brain-behavior relations.

PMID- 8546858
TI  - The neuropathology of parkinsonism: an overview.
AB  - The neuropathology of parkinsonism is reviewed as it occurs in primary
      (idiopathic) and secondary extrapyramidal syndromes. Present understanding of the
      significance of Lewy bodies in Parkinson's disease, diffuse Lewy body disease,
      and Lewy body variant of Alzheimer's disease is emphasized. The neuropathology
      produced by a variety of secondary causes is also considered to demonstrate the
      diverse lesions that can result in parkinsonism.

PMID- 8546859
TI  - The cardiovascular responses to feeding in man.

PMID- 8546860
TI  - The effect of mechanical loading on the response of rat ventricular myocytes to
      acidosis.
AB  - The effect of mechanical loading on the negative inotropic effect of acidosis in
      isolated rat ventricular myocytes was investigated. The mechanical loading of the
      myocytes was changed by attaching carbon fibres to the ends of the cell. To
      monitor intracellular Ca2+ and Na+ concentrations, cells were loaded with
      fluorescent dyes (fura-2 for Ca2+ and SBFI for Na+) using the acetoxymethyl (AM)
      esters. Mechanical loading reduced cell shortening by 73.0 +/- 3.5% (mean +/-
      S.E.M., n = 16) and abbreviated the time course of contraction. CO2-induced
      acidosis caused a rapid decrease in contraction followed by a slow partial
      recovery. The percentage changes in contraction were not significantly different
      in mechanically loaded and unloaded conditions. Mechanical loading had little
      effect on the time course of contraction during acidosis. Changes in
      intracellular Ca2+ and Na+ concentrations during acidosis were unaffected by
      mechanical loading. The mechanical loading conditions of a region of the heart
      can be modified by ischaemia and the subsequent acidosis. Our results suggest
      that the response of cardiac muscle to acidosis is not markedly modified by such
      changes in mechanical loading.

PMID- 8546861
TI  - Effect of calcitonin, elevated calcium and extracellular matrices on superoxide
      anion production by rat osteoclasts.
AB  - The electrochemical determination of superoxide anion generation by isolated
      mammalian osteoclasts was carried out by employing cytochrome c, immobilized at a
      surface-modified gold electrode. Osteoclasts cultured on bone generated 15-fold
      more superoxide anions than cells plated on plastic. Superoxide anion production
      by osteoclasts cultured on bone was almost completely abolished by salmon
      calcitonin, and partially abolished following exposure to elevated extracellular
      calcium. We therefore conclude that osteoclast activity is influenced
      substantially by the extracellular matrix.

PMID- 8546862
TI  - Regional differences in the contractile and intracellular Ca2+ responses of the
      guinea-pig vas deferens to neurotransmitters and excess K+.
AB  - The contractile responses to various concentrations of noradrenaline (NA),
      adenosine triphosphate (ATP), acetylcholine (ACh) and excess external K+ in the
      epididymal, middle and prostatic portions of the guinea-pig vas deferens were
      investigated by measuring the isotonic contraction, and the intracellular Ca2+
      concentration ([Ca2+]i) using fura-2 fluorescence. In the epididymal portion, the
      contractions evoked by each of these agonists were biphasic, comprising a
      transient followed by a tonic phase. In the middle portion, NA and ACh evoked
      biphasic contractions, whereas the ATP-induced contraction was an almost
      monophasic transient. In contrast, in the prostatic portion, only transient
      contractions were evoked by ACh and ATP, while the NA-induced contraction was
      oscillatory. The responses to each of the neurotransmitters in the three portions
      were not affected by pretreatment with TTX. The maximal responses of tonic
      contraction in response to each of the neurotransmitters were largest in the
      epididymal portion, decreased in the middle and were almost absent in the
      prostatic portion. These regional differences in the contractile properties of
      the vas deferens were also evident upon stimulation with excess external K+. As
      with the contractile responses, regional differences in the [Ca2+]i increases
      were observed during exposure to all the stimulants. It is suggested that the
      regional differences in the contractile responses of the vas deferens to various
      neurotransmitters and excess external K+ may involve variation in the mechanisms
      of Ca2+ homeostasis and in the sensitivity of the contractile apparatus to
      intracellular Ca2+ ions.

PMID- 8546863
TI  - Selective transport of microparticles across Peyer's patch follicle-associated M
      cells from mice and rats.
AB  - M cells are specialized structures in the Peyer's patch follicle-associated
      epithelium capable of taking up bacteria, viruses and other pathogens for later
      presentation to the gut-associated lymphoid tissue. The present work studies how
      coating microspheres with different proteins affects their ability to be taken up
      by M cells under near physiological conditions in vivo. The later appearance of
      microspheres in intestinal lymph has also been measured by flow cytometry. The
      protein preparations used in these experiments included bovine serum albumin
      (bSA), human immunoglobulin G (hIgG), secretory immunoglobulin A (hIgA), bovine
      growth hormone (bGH) and bGH complexed with an IgG antibody raised against bGH
      (bGH-Ab). Selectivity in binding of these microspheres to M cells, determined by
      confocal microscopy, was bGH < bSA < hIgG (mice) and bGH < bGH-Ab (rats and
      mice). A similar selectivity was seen for microsphere entry into M cells (bGH <
      bSA < hIgG; bGH < bGH-Ab). The appearance of protein-coated microspheres in rat
      mesenteric lymph showed a similar selectivity to that found for binding and entry
      into M cells (bGH < bGH-Ab). This latter selectivity was also found for hIgA
      coated microspheres (bSA < hIgA). Preservation of transport selectivity
      throughout transcytosis highlights the unique importance of the M cell surface as
      being the primary site determining which type of antigen can be presented
      subsequently to the gut immune system. The possibility that this is a transient
      or phasic property of the M cell surface and that this could have physiological
      relevance is also discussed.

PMID- 8546864
TI  - Insulin stimulates cationic amino acid transport activity in the isolated
      perfused rat pancreas.
AB  - The effects of exogenous insulin, glucagon and streptozotocin-diabetes on influx
      (15 s) of L-lysine via a cationic amino acid transporter resembling system y+
      were investigated in the isolated perfused rat pancreas. In non-diabetic
      pancreata, transport of L-lysine was saturable with an apparent Km of 2.11 +/-
      0.29 mM and Vmax of 2.21 +/- 0.20 mumol min-1 g-1 (n = 6). Bovine insulin (100 mu
      u ml-1) increased the maximal transport rate (Vmax = 3.49 +/- 0.30 mumol min-1 g
      1, n = 4, P < 0.05) for L-lysine 1.6-fold without altering the Km. L-Lysine
      transport was not elevated significantly in diabetic pancreata, although insulin
      (100 mu u ml-1) enhanced transport to values measured in non-diabetic
      preparations. Human glucagon (1.5 x 10(-9) M) had no stimulatory effect on L
      lysine transport. These findings provide the first evidence that exogenous
      insulin stimulates cationic amino acid transport activity in the exocrine
      pancreatic epithelium. Activation of the cationic pancreatic amino acid
      transporter may provide a mechanism to enhance the supply of L-arginine and thus
      sustain nitric oxide-mediated pancreatic secretion in response to islet hormones
      and secretagogues.

PMID- 8546865
TI  - Cardiovascular responses to heat stress in late gestation fetal sheep.
AB  - Heat stress during pregnancy in sheep is associated with respiratory alkalosis in
      both the mother and fetus, and, if prolonged, fetal growth is retarded. In seven
      pregnant sheep at 130-137 days gestation we used 15 microns diameter radioactive
      microspheres to determine the effect of raising the environmental temperature
      from 20 to 43 degrees C for 8 h on uteroplacental blood flows and the
      distribution of cardiac output in the ewe and fetus. Fetal cardiac output
      increased slightly from 47.0 +/- 3.2 (mean +/- S.E.M.) to 54.0 +/- 3.6 ml min-1
      (100 g tissue)-1, fetal arterial pressure and heart rate were unchanged, and
      total vascular conductance in the fetus increased significantly from 12397 +/-
      1111 to 14732 +/- 1569 ml min-1 kg-1 mmHg-1 (P < 0.01). Tissue blood flows (in ml
      min-1 (100 g)-1) increased significantly (P < 0.05) in the fetal body (e.g. nasal
      mucosa, torso and foreleg skin, adrenal, thyroid and thymus glands, brown and
      omental fats, heart, urinary bladder and carcass) and the fetal brain (e.g.
      cerebellum, cerebral grey matter, cervical spinal cord and pituitary gland).
      These regional vasodilatations occurred despite a significant fall (P < 0.01) in
      fetal arterial O2 saturation (55.2 +/- 1.8 vs. 38.6 +/- 2.4%), PO2 (18.1 +/- 0.7
      vs. 13.5 +/- 0.8 mmHg) and PCO2 (51.0 +/- 1.8 vs. 36.1 +/- 2.3 mmHg); under
      normothermic conditions hypoxia is associated with peripheral vasoconstriction.
      Because hypocapnia would also be expected to cause cerebral vasoconstriction it
      is suggested that during hyperthermia, hypoxia- and hypocapnia-induced
      vasoconstrictions are reduced by the release of vasodilator substances, or a
      decrease of sympathoadrenal effector responses. Blood flow to the fetal and
      maternal sides of the placenta did not change during the heat stress, suggesting
      that perfusion-dependent transfer of heat from fetus to mother across the
      placenta does not increase under hyperthermic conditions.

PMID- 8546866
TI  - Impact of gestational age on the catecholamine responses of the fetal sheep
      adrenal to cholinergic stimulation in vitro.
AB  - We have used the retrograde perfused adrenal preparation to investigate the
      catecholamine responses of the fetal sheep adrenal to increasing doses of
      acetylcholine (ACh) and excess potassium. Adrenal glands were collected from
      fetal sheep between 84 and 99 days gestation (before innervation; n = 7), between
      103 and 113 days gestation (during innervation; n = 8) and between 137 and 144
      days (after innervation; n = 9). Whilst the basal output of noradrenaline (NA)
      did not change between 84 and 144 days gestation, there was a significant
      increase in the adrenal output of adrenaline (Adr) between 84 and 144 days. The
      NA response to submaximal doses of ACh (10-10(3) microM) was significantly
      greater (P < 0.05) between 84 and 99 days gestation (mean NA response: 49.6 +/-
      11.4 nmol/(30 min)) than after 137 days gestation (mean NA response: 27.3 +/- 8.3
      nmol/(30 min)). Similarly, when the NA response to 10-10(3) microM ACh was
      expressed as a proportion of the maximal NA response to 10(4) microM ACh, the
      proportional NA response was greater at 84-99 days (48.9 +/- 11.3% of maximal)
      than at 137-144 days gestation (27.2 +/- 8.3%). The adrenal NA and Adr responses
      to 10(3) microM ACh between 84 and 137 days were reduced by up to 99% after the
      addition of hexamethonium. It appears, therefore, that the fetal adrenal is
      responsive to ACh before the development of innervation of the gland. There is
      also a decrease in sensitivity of the NA-secreting cells to submaximal doses of
      ACh as gestation progresses, which is not associated with a decrease in the size
      of the releasable pool of NA in the fetal adrenal. We speculate, therefore, that
      innervation of the fetal adrenal may be associated with an increase in the
      excitation threshold of the NA cells to nicotinic stimulation.

PMID- 8546867
TI  - Environmental effects on thermoregulation and breathing patterns during early
      postnatal development in hand-reared lambs.
AB  - This study examines the effect of hand-rearing developing lambs in a warm (WR; 25
      degrees C) or cool (CR; 10-15 degrees C) ambient temperature on the control of
      thermoregulation and breathing patterns, when maintained at a fixed level of
      nutrition over the first month of postnatal life. Measurements were made during
      non-rapid eye movement sleep whilst lambs were maintained for at least 1 h at
      warm (28-19 degrees C) and cold (14-5 degrees C) ambient temperatures at 1, 7, 14
      and 30 days of age. All lambs were able to maintain normal body temperature, but
      oxygen consumption was higher in CR lambs at 14 and 30 days of age. At 1 day of
      age shivering was rarely observed in any lambs, but at 7 and 14 days of age more
      WR than CR lambs responded to cold exposure via shivering. Plasma concentrations
      of triiodothyronine were higher at 7 and 14 days of age in CR lambs. Breathing
      frequencies were similar in WR and CR lambs, and from 7 days of age the incidence
      of expiratory laryngeal braking was higher in warm compared with cold study
      temperatures. By 30 days of age the recruitment of this mechanism was greater in
      CR lambs. Mean growth rate was slower over the first week of postnatal life in CR
      compared with WR lambs. This difference decreased over the first month of life,
      as growth rate increased from 83 to 130 g day-1 in the CR group but remained
      constant at approximately 150 g day-1 in the WR lambs. Total weight of the lungs
      and heart, but not the liver, were lower at 1 month but not at 1 week of
      postnatal life in CR lambs. It is concluded that a modest decrease in the ambient
      temperature in which postnatal lambs are reared, when on a fixed feed intake,
      alters lung size, the recruitment of laryngeal braking and the control of body
      temperature.

PMID- 8546868
TI  - The role of the endothelium in hypoxic pulmonary vasoconstriction.
AB  - The precise mechanisms underlying hypoxic pulmonary vasoconstriction (HPV) are
      still elusive. The recent discovery of K+ channels that are depressed by hypoxia
      in pulmonary vascular smooth muscle has provided a potential signal transduction
      mechanism for linking a reduction in Po2 to Ca2+ entry, but there are many
      reports suggesting that sustained HPV depends on the presence of the endothelium.
      Many endothelium-derived vasoactive factors have been investigated as possible
      mediators of HPV, including endothelium-derived relaxing factor (EDRF-NO),
      leukotrienes, prostanoids and endothelin, yet none have been found to be
      indispensable for HPV. They do, however, act as powerful modulators of the
      response to hypoxia. HPV is probably multifactorial in origin, as exemplified by
      the biphasic response to hypoxia seen in isolated pulmonary arteries over 40 min.
      The first phase is of rapid onset but transient, endothelium independent and
      partly related to Ca2+ release from intracellular stores. The second phase is
      slowly developing but sustained, dependent on the endothelium and associated with
      a stable elevation of cytosolic Ca2+. Since tension continues to rise while
      intracellular [Ca2+] remains constant, this implies Ca2+ sensitization of the
      contractile apparatus. This is independent of protein kinase C or pH. It is
      proposed that HPV depends upon both smooth muscle and endothelium resident
      mechanisms. Inhibition of K+ channels causes an elevation of cytosolic Ca2+,
      which may not be sufficient to generate substantive contraction on its own.
      However, release from the endothelium of an as yet unidentified mediator
      increases Ca2+ sensitivity of the contractile apparatus, and sustained
      contraction ensues.

PMID- 8546869
TI  - Hypoxic and metabolic regulation of voltage-gated K+ channels in rat pulmonary
      artery smooth muscle cells.
AB  - Inhibition of voltage-gated K+ (Kv) channels by 4-aminopyridine (4-AP)
      depolarizes pulmonary artery (PA) smooth muscle cells, induces Ca(2+)-dependent
      action potentials and increases [Ca2+]i. Neither charybdotoxin, which blocks
      Ca(2+)-activated K+ channels, nor glibenclamide, which blocks ATP-sensitive K+
      channels, has such effects on membrane potential (Em) and [Ca2+]i. Hypoxia
      reversibly decreases the 4-AP-sensitive KV currents (IK(V)) in PA myocytes. The
      resulting membrane depolarization caused by decreased IK(V) induces Ca(2+)
      dependent action potentials and thereby raises [Ca2+]i. Thus, KV channel activity
      plays a critical role in: (a) regulating Em and [Ca2+]i under physiological
      conditions; and (b) sensing O2 alteration and transducing the hypoxic stimulus to
      changes of Em and [Ca2+]i. The metabolic inhibitors 2-deoxy-D-glucose (2-DOG; 10
      mM) and carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP; 3-5 microM),
      the reducing agent reduced glutathione and inhibitors of cytochrome P-450, all
      mimic the effects of hypoxia on IK(V) and Em in PA myocytes. Furthermore, hypoxia
      and 2-DOG negligibly affect IK(V) and Em in mesenteric artery smooth muscle
      cells. These results suggest that hypoxia, perhaps via a localized reduction of
      ATP, triggers the block of KV channels and depolarizes PA myocytes. This blockade
      may also be mediated by a change in cellular redox status, perhaps via a
      conformational change of a haem- (or metal-) containing regulatory moiety that is
      attached to the channel protein.

PMID- 8546870
TI  - Ca(2+)-activated Cl- and K+ channels and their modulation by endothelin-1 in rat
      pulmonary arterial smooth muscle cells.
AB  - Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1;
      0.8-16 nM) enhanced a voltage-activated outward current (Iout) and induced
      periodic oscillations of inward current in smooth muscle cells isolated from
      small pulmonary arteries (200-400 microns in diameter). Anion substitution
      experiments revealed that the ET-1-induced inward current was carried by Cl-
      ions. Application of bosentan (10 microM; and ETA and ETB receptor antagonist)
      and FR 139317 (1-10 microM; a selective ETA receptor antagonist) prevented
      initiation of inward currents or enhancement of Iout by ET-1. The ETB receptor
      agonist tetra-Ala-endothelin-1 (1-20 nM) failed to evoke these responses.
      Caffeine (10 mM) induced a single transient inward current and prevented any
      further activation of inward current, or enhancement of Iout, by subsequent
      application of 16 nM ET-1, suggesting that these currents were mediated by Ca2+
      release from internal stores. Rapid intracellular release of Ca2+ by photolysis
      of nitr-5 activated an inward Cl- current and increased the magnitude of Iout.
      These results demonstrate the existence of Ca(2+)-activated Cl- and K+ channels
      in pulmonary arterial smooth muscle. The physiological role of these channels is
      at present uncertain, although their activation may be involved in the
      contractile responses of pulmonary arterial smooth muscle to ET-1.

PMID- 8546871
TI  - Opposing effects of oxidants and antioxidants on K+ channel activity and tone in
      rat vascular tissue.
AB  - K+ channels regulate tone in both the systemic and pulmonary circulations. K+
      channel inhibition leads to membrane depolarization, Ca2+ influx and
      vasoconstriction; K+ channel activation leads to hyperpolarization and
      vasodilatation. The sulfhydryl oxidant diamide opens K+ channels in pulmonary
      smooth muscle and acts as a potent vasodilator in perfused lungs. We examined the
      hypothesis that antioxidants cause constriction and oxidants cause relaxation
      through their effects on K+ channels in vascular smooth muscle. The oxidant
      diamide (380 microM and 3.8 mM) inhibited the reduction of cytochrome C by
      ferrous sulphate in vitro whilst the antioxidants co-enzyme Q10 (770 microM) and
      duroquinone (700 microM) increased the rate of reduction. Both antioxidants
      caused dose-dependent constriction of endothelium-intact and -denuded rat
      pulmonary artery and aortic rings. This constriction could be reversed by 1
      microM diamide. Co-enzyme Q10 and duroquinone (both at 100 microM) partially
      inhibited (approximately 30%) whole-cell K+ channel currents and depolarized
      membranes of isolated pulmonary artery smooth muscle cell recorded using the
      amphotericin-perforated-patch-clamp technique. Diamide (100 microM) increased
      whole-cell K+ channel currents and hyperpolarized the membrane. The data suggest
      that oxidants and antioxidants may modulate vascular tone via an effect on K+
      channels.

PMID- 8546873
TI  - Development of the normal and hypertensive pulmonary vasculature.
AB  - Normal adaptation to extra-uterine life consists of an immediate increase in
      endothelial and smooth muscle cell (SMC) surface: volume ratio as the cells
      'spread' in the vessel wall. Lumen diameter increases and resistance falls.
      Changes in SMC shape are associated with a transient depolymerization of
      contractile and cytoskeletal filaments. The four SMC phenotypes identified in the
      vessel wall rapidly show postnatal changes in the types of filament proteins and
      contractile-associated proteins, indicating that the term 'differentiation' means
      little at this age. At birth, all SMCs have a predominantly synthetic phenotype.
      Endothelium-dependent relaxation is relatively poor despite abundant nitric oxide
      synthase. SMCs are relatively insensitive to nitric oxide despite a high basal
      generation and a stimulated increase in cGMP generation. By contrast, the
      relaxation in response to ATP-sensitive potassium (KATP) channel activation is
      present at birth, the response being similar to that seen in the adult. Neonatal
      pulmonary hypertension, due to either congenital heart disease or experimental
      chronic hypobaric hypoxia (51 kPa) is associated with abnormal structural
      remodelling. In experimental pulmonary hypertension, the normal maturation of
      endothelium-dependent and -independent relaxation via soluble guanylate cyclase
      is delayed in newborns and the established responses are inhibited in older
      animals. The relaxant response to KATP channel activation is preserved. Thus,
      adaptation to extra-uterine life consists of a rapid sequence of integrated
      morphological and functional changes, which is disturbed by the presence of
      pulmonary hypertension. The pattern of recovery from a pulmonary hypertensive
      insult is determined by the age at exposure and type and duration of the insult.

PMID- 8546872
TI  - Redox agents as a link between hypoxia and the responses of ionic channels in
      rabbit pulmonary vascular smooth muscle.
AB  - Ca(2+)-activated K+ currents (IK(Ca)) and voltage-dependent Ca(2+)-insensitive K+
      currents (IK(V)) were recorded using the patch clamp technique to study the
      pulmonary (PASMC) and ear arterial smooth muscle cells (EASMC) of the rabbit and
      the possible regulatory mechanisms related to hypoxia. When a hypoxic solution (1
      mM Na2S2O4, gassed with 100% N2) was superfused, the activity of Ca(2+)-activated
      K+ channels (KCa channels) recorded at a pipette potential of -70 mV in cell
      attached mode was decreased to 49 +/- 7% in PASMC, whereas EASMC KCa channels did
      not respond to hypoxia. In inside-out patches (bathed symmetrically in 150 mM
      KCl), reducing agents such as dithiothreitol (DTT; 5 mM), reduced glutathione
      (GSH; 5 mM) and NADH (2 mM) decreased KCa channel activity in PASMC, but they did
      not affect the EASMC KCa channel. However, oxidizing agents such as 5,5'-dithio
      bis(2-nitrobenzoic acid) (DTNB; 1 mM), oxidized GSH (GSSG; 5 mM) and NAD (2 mM)
      increased KCa channel activity in both PASMC and EASMC. In the whole-cell
      configuration, using a pipette solution containing a high concentration of 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), PASMC IK(V)
      were activated by depolarizing step pulses to voltages more positive than -30 mV
      (holding potential, -80 mV). IK(V) was increased by application of a membrane
      permeable oxidizing agent, 2,2'-dithio-bis(5-nitropyridine) (DTBNP; 200 microM),
      whereas it was decreased by application of DTT (5 mM). From these results, it
      could be suggested that hypoxic pulmonary vasoconstriction is attributable, at
      least in part, to a change of cellular redox state, which decreases outward K+
      currents. This hypothesis is further supported by the observation that the basal
      redox state of EASMC KCa channels is more reduced than that of PASMC KCa
      channels. The distinct responses to hypoxia of pulmonary and systemic arterial
      smooth muscle could be explained by this difference.

PMID- 8546874
TI  - Lung disease and pulmonary endothelial nitric oxide.

PMID- 8546875
TI  - Clinical aspects of hypoxic pulmonary vasoconstriction.
AB  - Although frequently unrecognized, hypoxic pulmonary vascular disease is an
      important cofactor in the morbidity and mortality of a wide spectrum of disease
      processes. The hypoxic response incorporates two distinct phases, the acute
      hypoxic vasoconstrictor response and vascular remodelling associated with
      prolonged alveolar hypoxia. Understanding of the mechanisms causing both
      processes has increased rapidly and may result in the near future in specific
      treatment aimed at correcting underlying physiological abnormalities. However,
      currently available therapies remain limited to correction of the hypoxaemia and
      generalized non-specific pulmonary vasodilatation. The recent development of
      inhaled NO therapy represents a significant advance in the management of the
      acute hypoxic pulmonary vasoconstriction occurring during critical illness.

PMID- 8546876
TI  - Cold-induced changes in circulating levels of catecholamines and thyroid hormones
      are modulated by energy intake in newborn pigs.
AB  - Newborn pigs were kept at a low ambient temperature from 6 until 54 h of age and
      supplied with a limited (LI, 415 g (kg body weight)-1) or a high (HI, 655 g (kg
      body weight)-1) intake of milk. At the end of the treatment, both groups had
      similar deep body temperatures and metabolic rates. However, plasma adrenaline
      and noradrenaline levels were, respectively, 5.8- and 3.0-fold lower (P < 0.01)
      in HI than LI piglets, whereas plasma 3,5,3'-triiodothyronine (T3) was 1.5-fold
      higher (P < 0.01) in HI piglets. It is concluded that the hormonal control of
      cold-induced thermogenesis is modulated by energy intake, with catecholamines and
      thyroid hormones acting in a closely related and complementary manner.

PMID- 8546877
TI  - The effect of raised hydrostatic pressure on heart rate variability during breath
      holding in man.
AB  - Changes in cardiac interval (difference between two consecutive R waves of the
      ECG) during an expiratory breath hold (16 s) were examined in four divers during
      a saturation dive to 450 msw (metres of seawater). At 450 msw, breath hold caused
      a progressive shortening of cardiac interval that was significantly different
      from the changes seen at surface. The cause and significance of this shortening
      is unknown, but it might serve to maintain normal cardiovascular dynamics under
      hyperbaric conditions.

PMID- 8546878
TI  - The human B-lymphocyte response to Haemophilus influenzae type b capsular
      polysaccharide coupled to protein.

PMID- 8546879
TI  - Study of interaction between calcium and zinc on D-galactose intestinal
      transport.
AB  - Zinc is an essential trace element necessary to life. This metal may exert some
      of its physiological effects by acting directly on cellular membranes, either by
      altering permeability or by modulating the activity of membrane-bound enzymes. On
      the other hand, calcium is an essential element in a wide variety of cellular
      activities. The aim of the present work was to study a possible interaction
      between zinc and calcium on intestinal transport of D-galactose in jejunum of
      rabbit in vitro. In media with Ca2+, when ZnCl2 was present at 0.5 or 1 mM, zinc
      was found to reduce the D-galactose absorption significantly. In Ca(2+)-free
      media, where CaCl2 was omitted and replaced isotonically with choline chloride,
      the sugar transport was not modified by zinc. Verapamil at 10(-6) M (blocking
      mainly Ca2+ transport) did not modify the inhibitory effect of zinc on D
      galactose transport. When 10(-6) M of A 23187 (Ca(2+)-specific ionophore) was
      added with/without Ca2+ to the media, ZnCl2 produced no change in sugar
      transport. These results could suggest a possible interaction of calcium and zinc
      for the same chemical groups of membrane, which could affect the intestinal
      absorption of sugars.

PMID- 8546880
TI  - Selenium status, plasma zinc, copper, and magnesium in vegetarians.
AB  - Plasma zinc (Zn), copper (Cu), and magnesium (Mg) concentrations, copper/zinc
      ratio, and selenium (Se) status were studied in 44 vegetarians (22 males and 22
      females) and their age- and sex-matched nonvegetarians in the Bratislava region
      (Slovakia). Vegetarians had statistically significant lower levels of plasma Zn
      and Cu than nonvegetarians, which may be the result of lower bioavailability of
      Zn and Cu from this type of diet. No differences in plasma Mg levels were found
      between vegetarians and nonvegetarians. Se status, as expressed by plasma and
      erythrocyte concentrations and plasma and erythrocyte glutathione peroxidase
      activities (GPx), was significantly lower in vegetarians when compared to
      nonvegetarians. In the series as a whole, there were significantly higher
      correlations between plasma and erythrocyte Se concentrations and between plasma
      and erythrocyte GPx activities. Significant positive correlations were also found
      between plasma Se concentrations and erythrocyte GPx activities, and between
      erythrocyte Se concentrations and erythrocyte GPx activities. A vegetarian diet
      does not provide a sufficient supply of essential antioxidant trace elements,
      like Zn, Cu, and especially Se. Se supplementation should be recommended to this
      risk group of the population.

PMID- 8546881
TI  - Effects of metals on elastase from Pseudomonas aeruginosa SES-938-1.
AB  - Among the numerous virulance factors produced by Pseudomonas aeruginosa, elastase
      is the one most often associated with pathogenesis. In this study, effects of
      various metal ions on elastase from a new isolate of P. aeruginosa (Strain SES
      938-1) was investigated. Crude elastase was prepared from culture supernatant via
      salting out by ammonium sulfate, and then desalting and concentrating the sample
      using a centricon microconcentrator. Activities were measured at 450 nm using N
      succinyl-L-(ala)3-p-nitroanilide as the substrate. The metal chelating agents
      EDTA and EGTA inhibited the Pseudomonas elastase, which shows that the enzyme is
      a typical metalloproteinase. At a 10-mM concentration, Mn2+, Ni2+, and Zn2+
      strongly inhibited the elastase, whereas Mg2+ effect was negligable. There was a
      gradual decrease in the enzyme activity in accordance with an increase in the
      concentration of metal ions.

PMID- 8546882
TI  - Consistent relationship between selenium and apolipoprotein A-II concentrations
      in the sera of fasting middle-aged male abstainers and regular consumers of
      alcohol.
AB  - Several studies have suggested that selenium serum levels may be associated with
      serum lipids and apolipoproteins. In the present study, 99 clerical workers aged
      40-49 yr were selected based on their drinking and smoking habits. The serum
      concentration of selenium was not affected by these lifestyle factors. The
      regular drinkers had raised serum high-density lipoprotein cholesterol, apo A-I,
      and apo A-II concentrations. Correlation analysis showed that serum selenium was
      positively and consistently associated with apo A-II regardless of alcohol
      consumption. Factor analysis revealed that serum selenium had no association with
      factors that represented each lipoprotein fraction (LDL, HDL, and VLDL). The
      present study indicates that serum selenium is positively correlated only with
      apo A-II levels.

PMID- 8546883
TI  - Inhibition of PAF-acether effects on isolated guinea pig hearts by zinc ions
      (Zn2+).
AB  - PAF-acether is a phospholipid synthesized by most animal tissues and exerting a
      strong decrease on the heart's contractile force and coronary flow. PAF-acether
      (10(-9) and 10(-10)M) was administered to isolated guinea pig hearts perfused via
      the Langendorff apparatus with Chenoweth solution. Zinc (1.5 microM) is known to
      benefit heart function thus, Zn2+ (1.5, 7.5, and 30 microM) was added in the
      perfusing solution before or after PAF-acether administration. Contractile force,
      coronary flow, and heart rate were recorded by means of a Narco MK-IV Physiograph
      throughout all modes of perfusion. Calcium inhibitor (Verapamil 10(-10)M) and
      Pb+2 Co2+ (1.5 x 10(-6)M) were used subsequently in the perfusing solutions in
      order to elucidate some of the Zn and PAF interactions observed. All hearts were
      analyzed for their Zn and Ca content by means of an Atomic Absorption
      Spectrophotometry (AAS). Our data suggest that low concentrations of zinc (1.5
      microM) can strongly inhibit PAF-induced decrease of contractile force and
      coronary flow. Zinc-inhibiting effects on PAF's negative inotropic action
      (myocytic level) is not exerted through Zn-Ca antagonism. Nevertheless, a Zn-Ca
      antagonism in the arteriolar level cannot be excluded. Zinc inhibits PAF
      selectively only if it is administered before PAF injection and this strongly
      suggests a receptor interaction between the metal and the phospholipid at the
      heart level.

PMID- 8546884
TI  - Effect of daily hyperhydration on fluid-electrolyte changes in endurance-trained
      volunteers during prolonged restriction of muscular activity.
AB  - The aim of this investigation was to evaluate the effect of a daily intake of
      fluid and salt supplementation on fluid and electrolyte losses in endurance
      trained volunteers during prolonged restriction of muscular activity
      (hypokinesia). The studies were performed on 30 long-distance runners aged 23-26
      who had a peak oxygen uptake of 65.5 mL/kg/min and had taken 13.8 km/d on average
      prior to their participation in the study. The volunteers were divided into three
      groups: The volunteers in the first group were placed under normal ambulatory
      conditions (control subjects), the second group of volunteers subjected to
      hypokinesia alone (hypokinetic subjects), and the third group of volunteers was
      submitted to HK and consumed daily 0.1 g sodium chloride (NaCl)/kg body wt and 26
      mL water/kg body wt (hyperhydrated subjects). The second and third group of
      volunteers were kept under an average of 2.7 km/d for 364 d. During the pre
      experimental period of 60 d and during the experimental period of 364 d sodium,
      potassium, calcium, and magnesium in urine and plasma were determined. Blood was
      also assayed for osmolality, hemoglobin, hematocrit, plasma volume, plasma renin
      activity and plasma aldosterone. Mean arterial blood pressure was also
      determined. In the hyperhydrated volunteers plasma volume and arterial blood
      pressure increased, whereas plasma osmolality, plasma renin activity, plasma
      aldosterone, hematocrit, hemoglobin concentration, and urinary excretion and
      concentrations of electrolytes in plasma decreased. In the hypokinetic
      volunteers, plasma volume and arterial blood pressure decreased significantly,
      whereas hematocrit values, hemoglobin concentration, plasma osmolality, plasma
      renin activity, plasma aldosterone, and electrolytes in urine and plasma
      increased significantly during the experimental period. It was concluded that
      chronic hyperhydration may be used in minimizing fluid and electrolyte losses in
      endurance-trained volunteers during prolonged restriction of muscular activity.

PMID- 8546885
TI  - Impairment of motor coordination in mice after ingestion of aluminum chloride.
AB  - The mechanisms of aluminum (Al) neurotoxicity is of increasing interest. Al
      compounds are known to produce neurological and behavioral abnormalities in some
      mammalian species. The present study was designed to determine the effects of Al
      chloride on the skilled motor performance in mice on the rota-rod treadmill. Al
      chloride, depending on the duration of treatment, produced an impairment of the
      motor coordination ability in mice.

PMID- 8546887
TI  - Acute and chronic inflammatory mechanisms in asthma.

PMID- 8546886
TI  - Aluminum content of infant formulas used in Turkey.
AB  - In the past few years, there has been an upsurge of interest in aluminum (Al) and
      human health. The well-recognized manifestations of systemic Al toxicity include
      fracturing osteomalacia, dialysis encephalopathy, and microcytic hypochromic
      anemia. The role of Al in causing childhood diseases is also becoming clearer,
      but the safe plasma level still remains to be determined in newborns, especially
      in premature newborns, implying that it should be kept low. Premature infants
      receiving iv fluid therapy show evidence of Al loading. Additionally, the infant
      feeding mixtures, especially the soy-based infant formulas, tested may be a
      significant additional source of Al in the diet of infants with low birthweights,
      and in infants and in young children with impaired renal function. Careful
      clinical and biochemical monitoring is warranted to determine whether it will be
      necessary to eliminate Al contamination of both oral and parenteral preparations
      used in infants and children who may be at risk for Al intoxication. In this
      present study, the Al content of infant feeds was measured by electrothermal
      atomic absorption spectrophotometry, and also compared with those of breast milk,
      cow's milk, milk powder, and some starches that are commonly used for preparation
      of infant feed in Turkey. Our results show that Al content of commercially
      available powdered infant formulas, most of which are imported from Europe,
      ranged from 1.211 to 10.925 micrograms/g. The mean value was higher than that of
      breast milk. It was also found that the Al content of cow's milk in various
      containers was higher than that of breast milk. The highest Al level among cow's
      milk samples was in the aluminized carton box.

PMID- 8546888
TI  - Eformoterol and bronchial hyperresponsiveness in mild asthma.

PMID- 8546890
TI  - The clinical relevance of tachyphylaxis to beta 2 agonists.

PMID- 8546889
TI  - Continuous eformoterol and beta 2-receptor responsiveness.

PMID- 8546891
TI  - Cardiovascular and metabolic effects of eformoterol in adults.

PMID- 8546892
TI  - The place of long-acting beta 2 agonists in primary care.

PMID- 8546893
TI  - Eformoterol versus salbutamol in elderly patients with ROAD.

PMID- 8546894
TI  - Eformoterol in elderly patients: a follow-up.

PMID- 8546895
TI  - Eformoterol versus salbutamol in patients with ROAD.

PMID- 8546896
TI  - Enhanced risks of cancer from protracted exposures to X- or gamma-rays: a
      radiobiological model of radiation-induced breast cancer.

PMID- 8546897
TI  - bcl-2, p53 and proliferating cell nuclear antigen expression is related to the
      degree of differentiation in thyroid carcinomas.
AB  - Thyroid carcinomas are heterogeneous in terms of histology, clinical
      presentation, treatment response and prognosis. Since bcl-2 and p53 gene
      alterations are frequently involved in both lymphoid and epithelial malignancies,
      we analysed the expression of bcl-2, p53 and proliferating cell nuclear antigen
      (PCNA) in a group of 134 patients with thyroid neoplasms. The same markers were
      evaluated in fetal and adult normal thyroids as well as in 40 benign lesions. The
      study was carried out by immunocytochemistry on archival material using
      antibodies against bcl-2 and p53 protein on tissue sections of 40 adenomas (As),
      20 medullary carcinomas (MCs), 70 well-differentiated carcinomas (WDCs), 20
      poorly differentiated carcinomas (PDCs) and 24 undifferentiated carcinomas (UCs).
      bcl-2 immunoreactivity was detected in 36 out of 40 (90%) As, 20 out of 20 (100%)
      MCs, 60 out of 70 (85.7%) WDCs, 20 out of 20 (100%) PDCs, and 8 out of 24 (33.3%)
      of UCs. p53 expression was present in 11.4% of WDCs, 5% of PDCs, 5% of MCs and
      62.5% of UCs. By contrast, no p53 immunoreactivity was detected in 40 adenomas
      and in all the normal thyroid tissues studied. We observed a positive correlation
      between the expression of p53 and PCNA (r = 0.42; P = 0.035) in a group of UCs,
      but not in WDCs, PDCs and MCs. Neither p53 nor bcl-2 expression were correlated
      with clinicopathological parameters, such as age, sex, pTNM and survival. Our
      results suggest that in tumours of the follicular epithelium p53 and bcl-2
      protein abnormalities are associated with more advanced carcinomas and especially
      with undifferentiated carcinomas, while they are only rarely altered in tumours
      of the parafollicular C cells.

PMID- 8546898
TI  - Multiple regions of chromosome 6q affected by loss of heterozygosity in primary
      human breast carcinomas.
AB  - A total of 80 primary human breast carcinoma DNAs were analysed for loss of
      heterozygosity (LOH) on the long arm of chromosome 6, using microsatellite
      markers whose location has been defined physically and by linkage analysis. Loss
      of heterozygosity was observed in 38 of 80 (48%) tumours that were informative
      for at least one locus. The analysis revealed partial or interstitial deletions
      of chromosome 6q. Detailed mapping of chromosome 6q in these tumour DNAs
      identified two and perhaps three commonly deleted regions. One of these is
      located between markers D6S251 and D6S252 (6q14-q16.2), another between D6S268
      and D6S261 (6q16.3-q23) and a third between D6S287 and D6S270 (6q22.3-q23.1).

PMID- 8546900
TI  - MDA435/LCC6 and MDA435/LCC6MDR1: ascites models of human breast cancer.
AB  - We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen
      receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell
      line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo
      in nude mice and nude rats, with a tumour incidence of approximately 100%.
      Untreated mice develop ascites following i.p. inoculation of 1 x 10(6) cells and
      have a reproducible life span of approximately 30 days, with all animals dying
      within a 48 h period. The in vivo response of MDA435/LCC6 ascites to several
      cytotoxic drugs, including doxorubicin, etoposide (VP-16), BCNU and mitomycin C,
      closely reflects the activity of these single agents in previously untreated
      breast cancer patients. MDA435/LCC6 cells also retain the anchorage-dependent and
      anchorage-independent in vitro growth properties of the parental MDA-MB-435
      cells, and can be used in standard in vitro drug screening assays. The drug
      resistance pattern of the MDA435/LCC6 cells suggests that they may have few
      active endogenous drug resistance mechanisms. To generate a model for the
      screening of MDR1-reversing agents, MDA435/LCC6 were transduced with a retroviral
      vector directing the constitutive expression of the MDR1 cDNA, producing a cell
      line with a classical MDR1 resistance pattern (MDA435/LCC6MDR1). THese ascites
      models may be a viable alternative to the murine leukaemia ascites (L1210, P388)
      and, in conjunction with other breast cancer cell lines, facilitate the in vitro
      and in vivo screening of new cytotoxic drugs and drug combinations.

PMID- 8546899
TI  - Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer.
AB  - Presentation of endogenous antigenic peptides to cytotoxic T lymphocytes is
      mediated by the major histocompatibility complex (MHC) class I molecules. For the
      stable assembly of MHC class I complex it is necessary that the antigenic peptide
      is transported by the MHC-encoded transporters TAP-1 and TAP-2 into a pre-Golgi
      region. T-cell-mediated host-vs-tumour response might therefore depend on the
      presence of these molecules on tumour cells. The presence of MHC class I antigens
      and TAP-1 was studied in a series of 93 resection specimens of non-small-cell
      lung carcinomas (NSCLCs) by immunohistochemical methods using antibodies against
      the assembled class I molecule, beta 2-microglobulin (beta 2-m), heavy-chain A
      locus, A2 allele and TAP-1 protein. Eighty-six patients were included in the
      survival analysis. Total loss of class I molecule was observed in 38% of the
      cases and was usually accompanied by loss of beta 2-m and of heavy chain A locus.
      Selective loss of A locus was seen in 8.3% and of A2 allele in 27% of the cases.
      TAP-1 loss was always combined with beta 2-m and/or heavy chain A locus loss. No
      correlation was found between the expressional status of any of the above
      molecules, including the selective A2 allelic loss and histological type, degree
      of differentiation, tumoral stage, nodal stage and survival. Our findings suggest
      that loss of antigen-presenting molecules (including both MHC class I alleles and
      TAP-1) is a frequent event in lung cancer. However, the immunophenotypic profile
      of MHC class I and TAP-1 seems to be unrelated in vivo to the phenotype, growth
      or survival of NSCLC.

PMID- 8546901
TI  - Quantitative correlation of breast tissue parameters using magnetic resonance and
      X-ray mammography.
AB  - Previous investigators have shown that there is a strong association between the
      fraction of fibroglandular tissue within the breast as determined by X-ray
      mammography (per cent density) and breast cancer risk. In this study, the
      quantitative correlation between per cent density and two objective magnetic
      resonance (MR) parameters of breast tissue, relative water content and mean T2
      relaxation time, as investigated for 42 asymptomatic subjects. Using newly
      developed, rapid techniques MR measurements were performed on a volume-of
      interest incorporating equal, representative portions of both breasts. X-ray
      mammograms of each subject were digitised and analysed semiautomatically to
      determine per cent density. Relative water content showed a strong positive
      correlation with per cent density (Pearson correlation coefficient rp = 0.79, P <
      0.0001) and mean T2 value showed a strong negative correlation with per cent
      density (rp = -0.61, P < 0.0001). The MR and X-ray parameters were also
      associated with sociodemographic and anthropometric risk factors for breast
      cancer (P < 0.05). The potential use of MR parameters to assess risk of breast
      cancer and to provide a frequent, non-hazardous monitor of breast parenchyma is
      discussed.

PMID- 8546902
TI  - Inheritance of chromosome 7 is associated with a drug-resistant phenotype in
      somatic cell hybrids.
AB  - A major form of drug resistance in tumour cells known as classical multidrug
      resistance (MDR) is associated with the overexpression of the mdr1 gene product,
      the membrane protein P-glycoprotein (P-gp), which acts as an energy-dependent
      drug efflux pump. In this study the inheritance of P-gp expression was examined
      using hybrids formed after somatic cell fusion between a drug-sensitive human T
      cell leukaemia cell line, CEM/CCRF, and a drug-resistant derivative, CEM/A7,
      which is characterized by a clonal chromosomal duplication dup(7)(q11.23q31.2).
      Fourteen hybrids, chosen at random, were analysed by reverse transcriptase
      polymerase chain reaction (RT-PCR) and by binding studies involving the
      monoclonal antibody MRK16, which recognises an external P-gp epitope. Only two
      hybrids were positive for both MRK16 antibody labelling and mdr1 mRNA. Partial
      karyotypic analysis of all hybrids revealed that only the MRK16-positive hybrids
      contained the duplication in chromosome 7 seen in the CEM/A7 parental MDR line.
      Therefore, P-gp overexpression in the MRK16-positive hybrids may be linked to the
      inheritance of chromosome 7 from CEM/A7 and possibly associated with the
      chromosome 7 abnormality.

PMID- 8546903
TI  - Enhanced tumour specificity of an anti-carcinoembrionic antigen Fab' fragment by
      poly(ethylene glycol) (PEG) modification.
AB  - Polyethylene glycol (PEG) modification of a chimeric Fab' fragment (F9) of A5B7
      (alpha-CEA), using an improved coupling method, increases its specificity for
      subcutaneous LS174T tumours. PEGylation increased the area under the
      concentration-time curve (AUC0-144) in all tissues but there were significant
      differences (variance ratio test, F = 27.95, P < 0.001) between the proportional
      increases in AUC0-144, with the tumour showing the greatest increase. The
      increase in AUCtumour from F9 to PEG-F9 was similar to the reported increase from
      Fab' to F(ab')2 while the increase in AUCblood by PEGylation of F9 was only 21%
      of the reported increase from Fab' to whole IgG. A two sample t-test showed no
      significant differences between maximal tumour/tissue ratios for PEG-F9 and F9
      while the tumour/tissue ratios for PEG-F9 remained high over a longer period,
      with tumour levels at least double those for F9. PEG-F9 emerges as a new
      generation antibody with potential advantages for both radioimmunotherapy and
      tumour imaging. Since there was a reduction in antigen binding, optimisation of
      PEGylation might further improve tumour specificity. The latter resulted from
      complex effects on both the entry into and exit rates from tumour and normal
      tissues in a tissue-specific fashion.

PMID- 8546904
TI  - Modulation of vinblastine cytotoxicity by dilantin (phenytoin) or the protein
      phosphatase inhibitor okadaic acid involves the potentiation of anti-mitotic
      effects and induction of apoptosis in human tumour cells.
AB  - Cellular insensitivity to vinca alkaloids is suggested to be primarily due to
      drug efflux by P-glycoprotein (P-gp). The anti-epileptic phenytoin (DPH), which
      does not bind to P-gp, can selectively enhance vincristine (VCR) cytotoxicity in
      wild-type (WT) or multidrug-resistant (MDR) cells. We now demonstrate that the
      protein phosphatase inhibitor okadaic acid (OKA) can mimic the effect of DPH by
      selectively enhancing cytotoxicity of vinblastine (VBL), but not taxol and
      doxorubicin, in human leukaemia HL-60 cells. Both DPH and OKA potentiate the anti
      mitotic effects of VBL by enhanced damage to the mitotic spindle, resulting in
      prolonged growth arrest. Also, unlike VBL alone, in human leukaemia or non-small
      cell lung carcinoma cells treated with VBL plus DPH, recovery from damage to the
      mitotic spindle is compromised in drug-free medium and cell death by apoptosis in
      interphase ensues. Since protein phosphatases are involved with the regulation of
      metaphase to anaphase transit of cells during the mitotic cycle, enhanced VBL
      cytotoxicity in the presence of DPH or OKA may involve effects during metaphase
      on the mitotic spindle tubulin leading to growth arrest and apoptosis in
      interphase. These novel results suggest that DPH or OKA could be powerful tools
      to study cellular effects of vinca alkaloids and possibly for the development of
      novel therapeutic strategies.

PMID- 8546905
TI  - NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis,
      ameliorates interleukin 2-induced capillary leakage and reduces tumour growth in
      adenocarcinoma-bearing mice.
AB  - We tested whether NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide (NO) synthesis, can prevent interleukin 2 (IL-2)-induced capillary
      leakage in tumour-bearing mice without compromising the therapeutic benefits of
      IL-2. C3H/HeJ female mice transplanted s.c. with 2.5 x 10(5) C3-L5 mammary
      carcinoma cells were treated with: nothing, IL-2 (ten injections of 15,000 Cetus
      units i.p. every 8 h), L-NAME (0.1, 0.5, or 1 mg ml-1 drinking water), IL-2 + L
      NAME (0.1 or 0.5 or 1 mg ml-1 drinking water). Therapies were given in one round
      (IL-2, days 10-13; L-NAME, days 9-13) or in two rounds (IL-2, days 10-13 and 20
      23; L-NAME, days 9-13 and days 19-23) after tumour transplantation. Capillary
      leakage was measured from the water contents of the pleural cavities, lungs,
      spleen and kidneys. Effects of the therapies on the primary tumour size and the
      number of spontaneous lung metastases were also recorded. NO production was
      measured as the nitrite + nitrate levels in the serum and in the pleural
      effusion. After the first round of therapies, addition of L-NAME significantly
      reduced IL-2-induced pulmonary oedema and water retention in the spleen in a dose
      dependent manner. It also significantly reduced the IL-2-induced rise in NO
      levels in the serum and pleural fluid, but did not affect IL-2-induced pleural
      effusion or water retention in the kidney. At later stages of tumour growth (day
      23), tumours themselves induced significant fluid retention in the lungs and the
      kidney, which was not aggravated further with the second round of IL-2 therapy.
      At this time, L-NAME therapy alone ameliorated tumour-induced pulmonary oedema.
      During both rounds of therapy different doses of L-NAME alone caused a reduction
      of primary tumour growth as well as spontaneous lung metastases, which improved
      further with the addition of IL-2. The combination therapy was at least as
      effective as IL-2 therapy. In summary, L-NAME had anti-tumour effects in vivo,
      reduced the severity of IL-2-induced capillary leakage in some organs and did not
      compromise anti-tumour efficacy of IL-2 therapy. Thus, L-NAME could be a valuable
      adjunct to IL-2-based cancer therapy.

PMID- 8546906
TI  - Flow cytometric analysis of neoplastic nodules and hepatocellular carcinomas
      induced by ciprofibrate in the rat.
AB  - Alterations in DNA ploidy accompany hepatocellular carcinoma (HCC). However,
      changes in DNA content are also seen in regenerating liver and with increasing
      age. Thus, to investigate the role of DNA ploidy changes in development of HCC,
      flow cytometric DNA content determinations were done in a rat model system of
      peroxisome proliferator-induced HCC. Paraffin blocks of liver isolated from 18
      Fisher 344 male rats fed ciprofibrate for 20 weeks (4), 40 weeks (4) or 20 months
      (10) were examined. Livers from age-matched control rats were also examined. From
      the 20 month ciprofibrate group, nine neoplastic nodules (NNs), 27 HCCs and four
      non-tumorous surrounding tissue controls (NTCs) were examined. Significant DNA
      tetraploid populations were seen in both the NNs and NTCs. A significant increase
      in the percentage of DNA diploid cells was observed in the NN samples. No
      significant difference in the percentage S-phase cells was seen. Emergence of
      cell populations with new DNA ploidy classes (8c or DNA aneuploid) as compared
      with NTCs was only seen in HCCs (7 of 27), and five of these seven were DNA
      aneuploid, as distinct from DNA tetraploid, populations. A total of 16 of 24 HCC
      samples that were adequate for cell cycle analysis had average percent S-phase
      greater than the mean of the NTCs plus three standard deviations. Although a
      direct role cannot be inferred, these results support the hypothesis that
      increases in the fraction of diploid cells is an important early event in the
      development of rat HCC and that further alterations in DNA ploidy and increased
      proliferative fraction accompany the development of HCC.

PMID- 8546907
TI  - Extensive areas of aneuploidy are present in the respiratory epithelium of lung
      cancer patients.
AB  - According to the field cancerisation theory the entire upper aerodigestive tract
      has been mutagenised, thereby placing the affected individual at risk for the
      development of one or more cancers. To investigate this concept we studied the
      respiratory epithelium in lungs bearing cancer, including bronchi, bronchioles
      and alveoli. After identifying preneoplastic and preinvasive lesions by light
      microscopy, we determined the DNA content of their nuclei in Feulgen-stained
      sections using a high-performance digitised image analyser. Archival material
      from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected,
      including 16 central tumours (mainly squamous cell carcinomas) and 19 peripheral
      tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour
      from extrathoracic primary sites. Of the NSCLCs, 31/35 (89%) were aneuploid, as
      were 60% of the metastases from extrathoracic sites. Multiple, focal areas of
      preneoplasia or preinvasive carcinoma were present in the selected cases. The
      lesions ranged in severity from hyperplasia through metaplasia and dysplasia to
      carcinoma in situ. Aneuploid preinvasive lesions were not noted in association
      with the four diploid tumours but were present only when the accompanying NSCLC
      was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic
      lesions were more frequent in the peripheral parts of the lung (bronchioles or
      alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy
      increased with progressive severity of morphological change. Aneuploidy was not
      found in preinvasive lesions accompanying the five metastatic cases. Our findings
      provide strong support for the concept of field cancerisation.

PMID- 8546908
TI  - A late phase II study of RP56976 (docetaxel) in patients with advanced or
      recurrent breast cancer.
AB  - A late phase II clinical trial of RP56976 (docetaxel), derived from Taxus baccata
      was performed to evaluate anti-tumour activity, time to progression and clinical
      toxicity in patients with advanced or recurrent breast cancer. The patients,
      between 15 and 80 years old with performance status (PS) of 0-2, received at
      least two cycles of docetaxel 60 mg m-2 intravenously at 3-4 week intervals. Of
      the 81 patients enrolled, the 72 eligible for the study were given a total of 327
      cycles, with a median of four cycles each. Five patients obtained a complete
      response (CR) and 27 a partial response (PR); the response rate (RR) was 44.4%
      (95% confidence interval 32.7-56.6%). A relatively high RR of 9/28 (32.1%) was
      observed in patients who had received prior chemotherapy involving
      anthracyclines. The dose-limiting toxicity was grade 3-4 leucocytopenia or
      neutropenia, found in 78.9% and 85.9% patients respectively. Other severe (grade
      > 3) toxicities included alopecia (38%), anorexia (18.3%), nausea/vomiting
      (11.3%), and fatigue (9.9%). Hypersensitivity reactions, oedema and skin toxicity
      were not severe and were reversible. One therapy-related death occurred 10 days
      after the initial dose was given. These findings indicate that docetaxel has
      potent activity against metastatic breast cancer, and that the dose of 60 mg m-2
      is safe.

PMID- 8546909
TI  - Randomised trial for the prevention of delayed emesis in patients receiving high
      dose cisplatin.
AB  - Despite recent advances in control of acute emesis following cisplatin-based
      chemotherapy regimens, delayed emesis remains a significant cause of treatment
      related morbidity and factors associated with delayed emesis have not yet been
      evaluated. A prospective randomised trial was conducted to compare the efficacy
      and toxicity of granisetron, dexamethasone plus prochlorperazine with granisetron
      alone in controlling cisplatin-induced delayed emesis and to identify the
      important factors that influence its occurrence and severity. Seventy cisplatin
      naive patients with inoperable solid tumors participated in the trial. Patients
      who received 80 mg m-2 or 100 mg m-2 of cisplatin were randomly assigned to
      receive either granisetron 40 micrograms kg-1 intravenously (i.v.) on day 1,
      dexamethasone 20 mg i.v. on days 2 and 3 and prochlorperazine 5 mg orally thrice
      daily on days 1-5 or granisetron 40 micrograms kg-1 i.v. on day 1 alone. There
      was no difference in their acute antiemetic efficacy. A combination regimen was
      more effective than granisetron alone in preventing delayed symptoms, with
      superior rates of complete plus major responses of 77% vs 51% (P = 0.0460).
      Treatment arm was the only determinant factor for the occurrence of delayed
      emesis (P = 0.0101).

PMID- 8546910
TI  - What are the information priorities for cancer patients involved in treatment
      decisions? An experienced surrogate study in Hodgkin's disease.
AB  - A total of 165 adult patients with Hodgkin's disease (HD) were questioned
      following treatment to examine their perceptions of actual and desired
      involvement and provision of information in the treatment decision-making
      process. Irrespective of the degree to which patients felt they had been involved
      in the decision-making process and of the outcome of their particular treatment,
      patients who felt satisfied with the adequacy of information given were
      significantly more likely to feel happy with their level of participation in the
      overall process of decision-making (P < 0.001). As part of a strategy
      investigating patient priorities, patients were asked to rank a series of
      possible acute and late treatment-related morbidities. Counter-intuitively, the
      majority of long-term survivors felt early short-term side-effects were more, or
      equally, as important as late morbidity with respect to influencing choice of
      therapy. Unpredictable importance was placed by patients on side-effects such as
      weight gain and fatigue in relation to other complications such as infertility
      and risk of relapse. Patients do not necessarily share doctors' priorities in
      decision-making or place the same emphasis on different types of morbidity.
      Experienced surrogates may assist us in understanding patients' perspectives and
      priorities.

PMID- 8546911
TI  - Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62
      in head and neck or lung cancer.
AB  - The purpose of this study was to determine the effect of the first rat monoclonal
      antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I
      clinical trial in patients with unresectable squamous cell carcinomas. This
      antibody effectively blocks the binding of EGF, transforming growth factor (TGF)
      alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines
      which overexpress the EGFR and eradicates such tumours when grown as xenografts
      in athymic mice. Eleven patients with squamous cell carcinoma of the head and
      neck and nine patients with squamous cell carcinoma of the lung, whose tumours
      expressed EGFR, were recruited. Groups of three patients were treated with 2.5
      mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg.
      All patients were evaluated for toxicity using WHO criteria. Patients' sera were
      tested for the clearance of MAb ICR62 and the development of human anti-rat
      antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in
      patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be
      detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of
      ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and
      two at 100 mg doses) and of these only the former two were anti-idiotypic
      responses. In four patients receiving doses of ICR62 at 40 mg or greater,
      biopsies were obtained from metastatic lesions 24 h later and examined for the
      localisation of ICR62 using anti-rat antibody reagent. In these patients we
      showed the localisation of MAb ICR62 to the membranes of tumour cells; this
      appeared to be more prominent at the higher dose of 100 mg. On the basis of these
      data we conclude that MAb ICR62 can be administered safely to patients with
      squamous cell carcinomas and that it can localise efficiently to metastases even
      at relatively low doses.

PMID- 8546912
TI  - Lymphocyte recovery and clinical response in multiple myeloma patients receiving
      interferon alpha 2 beta after intensive therapy.
AB  - The recovery of immunoregulatory cells in the peripheral blood of patients with
      multiple myeloma receiving maintenance therapy with interferon alpha 2 beta (IFN
      alpha 2 beta) after intensive therapy with high-dose melphalan and autologous
      bone marrow or peripheral blood stem cell rescue was studied. IFN-alpha 2 beta
      significantly inhibited the recovery of CD3+, CD4+, CD8+, CD56+/CD3- and
      CD16+/CD3- lymphocytes compared with numbers found in patients who had no further
      post-transplant treatment, but had no effect on the recovery of CD19+ cells.
      Among patients who did not receive IFN-alpha 2 beta, the number of CD8+,
      CD56+/CD3- and CD16+CD3- lymphocytes recovered to values similar to normal
      volunteers with increasing time after intensive therapy, however the number of
      CD4+ cells remained significantly below levels found in normal volunteers.
      Although CD16+/CD3- and CD56+/CD3- cell numbers were reduced in patients
      receiving IFN-alpha 2 beta, natural killer (NK) activity was not affected. The
      levels of soluble interleukin 2 receptor (sIL-2R) were similar in all patients
      and IL-2 was not detected in any patient. At the time of writing, of the total of
      69 patients, seven have relapsed, of whom three were receiving IFN-alpha 2 beta,
      however there was no correlation between the absolute numbers of any lymphocyte
      subset with imminent relapse. The data suggest that the recovery of a specific
      lymphocyte subset(s) in peripheral blood is unlikely to be associated with the
      maintenance of response after intensive therapy.

PMID- 8546914
TI  - A case-control study of Hodgkin's disease and pregnancy.
AB  - To evaluate the role of pregnancy in the pathogenesis and clinical course of
      Hodgkin's disease (HD), we studied a series of 192 female patients aged 17-50
      years at the time of diagnosis, and 496 healthy controls matched by residence and
      year of birth. Cases showed a marginally significant excess for the father having
      a high level of education, and more families were classified as white-collar
      workers than as industrial workers. No significant differences between cases and
      controls were found in other parameters describing the family and living
      conditions in childhood. Before the age when cases were diagnosed, 35.4% of cases
      and 34.7% of their controls were nulliparous. Among the cases, the mean age at
      first delivery was 22.4 years, with a total of 201 children (average: 1.05 per
      case) born before diagnosis; for the controls, the corresponding figures were
      22.2 years and 573 children (average: 1.15). Within the first 6 months after the
      last delivery, HD was diagnosed in 12 of 124 parous cases (9.7%); for controls,
      the corresponding number is 18 out of 324 (5.6%). A marginally significant
      negative trend (P = 0.07) in odds ratios is seen with increasing duration of this
      interval. We conclude that our study could not confirm previous reports of a
      protective effect of pregnancy for the risk of HD. On the other hand, marked
      physiological changes in the period of puerperium may accelerate the expression
      of HD.

PMID- 8546915
TI  - The incidence of cerebral glioma in the working population: a forgotten cancer?
AB  - We studied the incidence of intracranial tumours in Lothian Region in south-east
      Scotland in 1989-90. Among 106 patients resident in the Region, 60 (57%) were of
      working age (15-64 years). All but two cases (97%) were histologically confirmed.
      The average annual incidence of cerebral glioma in this age range was 5.9 (95% CI
      3.8-8.0) per 100,000 per year. Cerebral glioma will affect approximately 2100
      people of working age in the UK every year.

PMID- 8546913
TI  - Application of the multidimensional fatigue inventory (MFI-20) in cancer patients
      receiving radiotherapy.
AB  - In this paper the psychometric properties of the multidimensional fatigue
      inventory (MFI-20) are established further in cancer patients. The MFI is a 20
      item self-report instrument designed to measure fatigue. It covers the following
      dimensions: general fatigue, physical fatigue, reduced activity, reduced
      motivation and mental fatigue. The instrument was used in a Dutch and Scottish
      sample of cancer patients receiving radiotherapy. The dimensional structure was
      assessed using confirmatory factor analyses (Lisrel's unweighted least-squares
      method). The hypothesised five-factor model appeared to fit the data in both
      samples (adjusted goodness of fit; AGFI: 0.97 and 0.98). Internal consistency of
      the separate scales was good in both the Dutch and Scottish samples with
      Cronbach's alpha coefficients ranging from 0.79 to 0.93. Construct validity was
      assessed by correlating the MFI-20 to activities of daily living, anxiety and
      depression. Significant relations were assumed. Convergent validity was
      investigated by correlating the MFI scales with a visual analogue scale measuring
      fatigue and with a fatigue-scale derived from the Rotterdam Symptom Checklist.
      Results support the validity of the MFI-20. The highly similar results in the
      Dutch and Scottish sample suggest that the portrayal of fatigue using the MFI-20
      is quite robust.

PMID- 8546916
TI  - Second primary cancers in patients with cutaneous malignant melanoma: a
      population-based study in Sweden.
AB  - To quantify the risk of second primary cancers among patients with cutaneous
      malignant melanoma, we studied 20,354 patients in the Swedish Cancer Register
      during 1958-88. A second primary cancer was reported in 1605 patients, compared
      with an expected number of 1109.5 [standardised incidence ratio (SIR) = 1.45, 95%
      confidence interval (CI) = 1.38-1.52]. The highest risk was found among patients
      younger than 60 years. The greatest risk was seen during the first year after
      diagnosis (SIR = 1.91, CI = 1.69-2.14), but even after long-term follow-up--15
      years or more--the risk was still significantly elevated (SIR = 1.56, CI = 1.35
      1.79). The strongest association was found for a second primary malignant
      melanoma (men, SIR = 10.0, CI = 8.26-12.00; women, SIR = 8.66, CI = 7.22-10.30)
      and non-melanoma skin cancer (men, SIR = 3.58, CI = 2.85-4.44; women, SIR = 2.41,
      CI = 1.71-3.29). The risk of second cancers associated with tissues of
      neuroectodermal origin was increased, especially tumours of the nervous system
      (men, SIR = 1.73, CI = 1.10-2.60; women, SIR = 2.03, CI = 1.45-2.78). The SIR of
      second cancers involving the immune system was also increased. An excess risk of
      endometrial cancer was seen (SIR = 1.41, CI = 1.03-1.88), but no significant
      associations existed for cancers of the breast, ovary, testis or other endocrine
      glands. Among tumours of the digestive tract, only colon cancer in men had a
      significantly increased SIR (1.33, CI = 1.00-1.74).

PMID- 8546917
TI  - More impact on EU nursing policies.

PMID- 8546918
TI  - Tragedy made worse.

PMID- 8546919
TI  - What budget means for nurses.

PMID- 8546920
TI  - Junior doctors' hours. Beat the clock.

PMID- 8546921
TI  - No action to end 'care lottery'.

PMID- 8546922
TI  - Workplace violence. Breaking the cycle.

PMID- 8546923
TI  - Archimedes meets granny.

PMID- 8546924
TI  - Modifying the body: piercing and tattoos.
AB  - This article examines body piercing and tattooing. The author describes the
      motives expressed by individuals undergoing these practices, the health and
      social consequences of body modification and the laws governing the procedures.
      The implications for healthcare professionals are also detailed.

PMID- 8546925
TI  - The best national health service in the world.

PMID- 8546926
TI  - Breaking bad news: caring for the family.

PMID- 8546927
TI  - Setting up a shared care glaucoma clinic.
AB  - This article describes how a nurse-led clinic to care for patients with glaucoma
      was set up and provides some initial evidence of its success. The authors also
      explain how they have developed the clinic further and their plans for the
      future.

PMID- 8546929
TI  - The role of the Commission for Racial Equality in tackling NHS racism.

PMID- 8546928
TI  - Palliative care: the nurse's role.

PMID- 8546930
TI  - Abortion--who needs support?

PMID- 8546931
TI  - Merger madness.

PMID- 8546932
TI  - Space travel, bed rest and nursing.

PMID- 8546933
TI  - Leadership in nursing: more than one way (continuing education credit).

PMID- 8546934
TI  - Are children who clear HIV truly uninfected?

PMID- 8546935
TI  - Strike threat still looms.

PMID- 8546936
TI  - Students have to slum it.

PMID- 8546937
TI  - Lights, camera, action!

PMID- 8546938
TI  - An old scourge returns.

PMID- 8546939
TI  - Dependency scoring in palliative care.
AB  - This article describes the development and implementation of a dependency rating
      tool for a palliative care unit. The author details how dependency scores were
      used to match the needs of patients and those close to them with staffing levels
      on the unit.

PMID- 8546940
TI  - Treating infertility in Roman Catholics.
AB  - This article sets out to assess Roman Catholic doctrine on the medical treatment
      of infertility, and the implications of that doctrine for infertile couples.
      Children are vitally important for a Catholic marriage to be perceived as
      successful. Couples wishing to seek medical treatment for infertility may
      experience enhanced stress due to restrictive Catholic doctrine, which prohibits
      the use of several modern treatments.

PMID- 8546941
TI  - Hypoglycaemia [continuing education credit].

PMID- 8546942
TI  - Healthy debate. Roll up, roll up; sell out of the century.

PMID- 8546943
TI  - Workface: know your rights.

PMID- 8546944
TI  - Raw deals for two wheels.

PMID- 8546946
TI  - Health services: the countdown continues ...

PMID- 8546945
TI  - Up to one's eyes.

PMID- 8546947
TI  - Embarking on a quality journey.

PMID- 8546948
TI  - Mental health. New number, same service.

PMID- 8546949
TI  - Rheumatology. Sharing care in an outpatient clinic.
AB  - Patients with rheumatoid arthritis require a multidisciplinary approach to their
      care that allows them as much control over their condition as possible. This
      article describes how a clinic led by a clinical nurse specialist and an
      occupational therapist has set out to achieve these aims.

PMID- 8546950
TI  - The experience of women during their partners' hospital stay after MI.
AB  - Structured interviews were undertaken with 159 women following their partner's
      myocardial infarction (MI) and 129 of these women completed a further postal
      questionnaire approximately three weeks later. While in hospital, only a quarter
      of women were spoken to by nurses about possible dietary change for their
      partners, 24 percent were advised about exercise and 11 percent about work.
      Thirty one percent were spoken to about general lifestyle of their partners. When
      asked to rate the usefulness of information from all sources about various
      topics, those women who had been spoken to by nurses had significantly higher
      scores three weeks post-MI than women who had not. Nurses were frequently not
      proactive in offering information to women who showed high levels of anxiety and
      depression at both time points. These findings are discussed in relation to the
      role of hospital nurses in secondary prevention strategies.

PMID- 8546951
TI  - Bionursing: confusion in elderly people.

PMID- 8546952
TI  - A day in the life: a night to remember.

PMID- 8546953
TI  - Personal finance: pension pitfalls.

PMID- 8546954
TI  - Tissue viability. Implementing pressure sore policy.

PMID- 8546955
TI  - Tissue viability. The costs of a pressure sore prevention policy.

PMID- 8546956
TI  - Nurses 'worth their weight in gold'.

PMID- 8546957
TI  - Principal posts unfilled.

PMID- 8546958
TI  - Practice and management awards. Gaining confidence and going places.

PMID- 8546959
TI  - Nurse practitioners. Life on the streets. Interview by Charlotte Alderman.

PMID- 8546961
TI  - The injustices suffered by black and ethnic minority nurses.

PMID- 8546960
TI  - Defining the future for school nursing.
AB  - This article examines some of the health needs of school-age children and
      adolescents within a changing society, and explores how school nurses can
      respond, and are responding to these needs. The author also considers an
      educational programme designed for school nurses of the future, which should
      enable graduate school nursing specialists to take their place alongside other
      community nursing and teaching colleagues.

PMID- 8546962
TI  - Joint education for mental health teams.
AB  - As health and social problems become more complex, the imperative for
      interdisciplinary professional education increases. Yet the clash of perspectives
      between professions has hindered the development of a common approach, and led to
      real power differentials. The challenge for higher education is to work with
      services to find models of education and training that translate into truly
      interdisciplinary clinical and community settings.

PMID- 8546963
TI  - Burns.

PMID- 8546964
TI  - Shaken, not spurned.

PMID- 8546965
TI  - Twinning teams.

PMID- 8546966
TI  - Tea and sympathy ... and Guinness too.

PMID- 8546967
TI  - The machine breaks.

PMID- 8546968
TI  - Cash threat to 'seamless care'.

PMID- 8546969
TI  - Action plans on racism.

PMID- 8546970
TI  - Promoting positive regard.

PMID- 8546972
TI  - What's in a name?

PMID- 8546971
TI  - Fateful faxes.

PMID- 8546973
TI  - Defining role models for staff orientation.
AB  - This article examines the need for a formal role model to help integrate new
      staff within a unit. While acknowledging the range of titles and functions
      ascribed to such a role in the literature, the author suggests that the essence
      of the role and its formal recognition has benefits for experienced staff and
      orientees alike.

PMID- 8546975
TI  - Are patient focused hospitals working?
AB  - The concept of patient focused hospitals has been with us since the 1980s. James
      Buchan looks at whether claims for the benefits of this type of care have been
      realised in practice.

PMID- 8546974
TI  - The new standard of admission within two hours.

PMID- 8546976
TI  - Bionursing: the role of hepatic enzymes.

PMID- 8546977
TI  - Managing chronic obstructive disease.
AB  - Chronic obstructive pulmonary disease is a term which encompasses a range of
      different conditions. This article explains the various presentations and
      discusses how patients should be managed.

PMID- 8546978
TI  - Using a handbook to improve nurses' continence care.
AB  - Nursing care should be based on sound research evidence with demonstrated
      clinical effectiveness. Dissemination of this research evidence is, therefore, of
      paramount importance. A study using focus groups was undertaken during 1993-1994
      to evaluate the dissemination of a clinical handbook for continence care to
      qualified nurses, in relation to reported nursing practice in care of the elderly
      wards/units in one health authority. A total of 124 nurses participated in the
      study and 98 variables were included. Improvements were recorded in nurses'
      responses between the pre-test and post-test for 84 (86 per cent) variables in
      the experimental group and 58 (59 per cent) in the control group. This
      demonstrates the positive value of the clinical handbook as a method of
      disseminating research evidence.

PMID- 8546979
TI  - A benchmark not a barrier.

PMID- 8546980
TI  - In the genes shop.

PMID- 8546981
TI  - Challenging racism.

PMID- 8546982
TI  - Can ultraviolet erythema be used to identify the basal cell carcinoma phenotype?
AB  - Since a prolonged duration of a strong UVB erythema has been suggested as a
      marker for propensity to develop skin cancer, we objectively followed the
      duration and intensity of erythemas induced by UVB and UVA radiation for 28 days
      in 18 patients with basal cell carcinoma (BCC), and in 15 healthy controls using
      reflectance spectrophotometry. The erythema index, defined as the difference in
      redness between UV-exposed skin and normal, adjacent skin on the lower abdomen,
      did not differ significantly between the two groups at 24 h, when the reaction
      was maximal, following a dose of 6 MED of UVB. Erythema values after 7 and 14
      days were slightly higher in the BCC group, but this difference did not reach
      statistical significance. At day 7 some patients in the BCC group showed very
      strong erythemas. At days 21 and 28 the two groups had almost identical erythemal
      reactions. Following a standard dose of UVA of 100 J/cm2, patients with BCC and
      healthy controls both showed weak erythemal reactions, which declined somewhat
      over the study period. No significant differences in pigmentary response were
      noted between the BCC and the control group, neither following UVB nor UVA.
      Although individual patients with BCC deviate from the normal erythemal curve for
      UVB, the UVB response is not a suitable predictive instrument in screening
      patients with the basal cell carcinoma phenotype.

PMID- 8546983
TI  - Phototoxic and photoprotective effects of topical isothipendyl.
AB  - Isothipendyl, an H1-receptor antagonist, is an antihistamine used as an
      antiallergic drug. Its molecular structure is close to the phenothiazines, but it
      has different photobiological properties. Like phenothiazines, isothipendyl is
      phototoxic with ultraviolet A (UVA) but it reduces the erythema response to UVB
      radiation. Isothipenyl seems to have the same protective properties as a
      sunscreen because its UVB protective properties are effective only if the
      substance is applied prior to exposure.

PMID- 8546984
TI  - Recurrent recall of sunburn by methotrexate.
AB  - An unusual recall reaction of sunburn with methotrexate use has been previously
      reported. Heretofore, all reports have documented a single occurrence of this
      reaction in each patient. We report, for the first time, a patient who developed
      recurrent facial sunburn recalls while receiving methotrexate for psoriasis. This
      reaction is distinct from true photosensitivity. Photosensitivity is listed in
      the drug brochure for methotrexate. However, a review of the literature does not
      support true photosensitivity associated with methotrexate.

PMID- 8546985
TI  - Re: Sayre R, Kollias N, Ley R, Baqer A. Changing the risk spectrum of injury and
      the performance of sunscreen products throughout the day.

PMID- 8546986
TI  - Biologic Effects of Light. Atlanta, Georgia, October 9-11, 1995. Abstracts.

PMID- 8546987
TI  - Enhancement of the depigmenting effect of hydroquinone by cystamine and
      buthionine sulfoximine.
AB  - Glutathione (GSH) performs several important biological functions, including
      quenching of reactive oxygen species, and protection of cells from toxic
      compounds such as quinones. The first step in the synthesis of GSH is catalysed
      by gamma-glutamylcysteine synthetase, an enzyme which is inhibited by cystamine
      and buthionine sulfoximine (BSO). In this study, we examined the possibility that
      the effect of hydroquinone (HQ) on pigmentation could be potentiated by
      inhibiting the production of GSH. In vitro studies using melanoma cell lines
      demonstrated that both cystamine and BSO could potentiate the inhibitory effects
      of HQ on tyrosinase activity and melanin content. A synergistic decrease in hair
      pigmentation was observed when a combination of HQ (2 or 4%) and BSO (5%) was
      applied to the dorsal skin of C57BL mice. In black hairless guinea-pigs, the
      application of HQ plus either BSO or cystamine resulted in a significant decrease
      in epidermal pigmentation when compared with any of the agents alone. The
      possibility exists that in the future a combination of HQ plus cystamine or BSO
      could be used to treat disorders such as melasma and post-inflammatory
      hyperpigmentation.

PMID- 8546988
TI  - Irritant susceptibility and weal and flare reactions to bioactive agents in
      atopic dermatitis. I. Influence of disease severity.
AB  - The two main pathogenetic characteristics of atopic dermatitis (AD) are: (i)
      antigen-dependent 'specific' reactivity, and (ii) altered non-immunological 'non
      specific' reactivity. Our understanding of the role of non-specific reactivity is
      hampered by the fact that methods available for its quantification are limited.
      The aim of the present study was to assess the usefulness of two parameters as
      quantitative measures of non-specific skin reactivity in AD: (i) susceptibility
      to repeated epicutaneous exposure to an irritant (sodium lauryl sulphate, SLS),
      assessed by visual scoring and transepidermal water loss (TEWL) measurement, and
      (ii) reactivity to intracutaneously injected bioactive agents (codeine, FMLP,
      histamine, methacholine, substance P, trypsin), assessed by measurement of weal
      and flare size. These two parameters were tested in a group of AD patients,
      subdivided according to the severity of their dermatitis, and a control group.
      The visual score and TEWL after SLS exposure tended to be higher in the AD group
      than in the control group. Furthermore, visual score and post-exposure TEWL were
      positively correlated with the dermatitis severity score. Weal size following
      injection of codeine, histamine and substance P, and flare size following
      injection of all agents, except methacholine, were significantly lower in the AD
      group than in the control group. Negative correlations were found between weal
      and flare sizes and the dermatitis severity score. These findings can be
      explained by down-regulation of structures involved in weal and flare reactions.
      In conclusion, we propose that epicutaneous irritant susceptibility and
      reactivity to intracutaneous bioactive agents may be useful indicators of non
      specific skin reactivity in AD.

PMID- 8546990
TI  - Immunohistochemical evidence for differential distribution of 5 alpha-reductase
      isoenzymes in human skin.
AB  - Antibodies raised against fragments of synthetic peptides of human 5 alpha
      reductase isoenzymes 1 (h5 alpha r1) and 2 (h5 alpha r2) were applied to paraffin
      sections of human skin (scalp, eyelid, lip, breast, scrotum). Immunoreactive
      sites were differentially distributed, in that h5 alpha r1 immunoreactivity was
      present in the nuclei of cells in the stratum germinativum (basal and lower
      portion of the spinous layer) of the epidermis, subepithelial fibroblasts,
      adipocytes, smooth muscle cells of the scrotal tunica dartos, basal cells of
      sebaceous glands, excretory duct cells of sweat glands, cells of the dermal
      papilla and fibrous and outer epithelial sheath of hair roots, as well as
      endothelial cells of small vessels and Schwann cells of cutaneous myelinated
      nerves. In contrast, immunoreactivity for h5 alpha r2 was found in the cytoplasm
      of the cells of the spinous layer (and far less intensely in the basal layer) of
      the epidermis, subepidermal fibrocytes, and especially in subcutaneous
      adipocytes. Immunoreactivity was strongest in the non-keratinized portion of the
      inner epithelial sheath and the cuticle of hair follicles, whereas other portions
      of the hair root were negative. Sweat glands were stained, whereas sebaceous
      glands showed only weak diffuse immunoreactivity. In mucocutaneous zones,
      salivary glands and conjunctival epithelium showed immunoreactive cells. Vascular
      endothelium displayed immunoreactivity only in the genital region. We present
      experimental evidence for a differential distribution of 5 alpha-reductase
      isoenzymes in human skin. This might reflect a diversity in the response of
      different areas of the skin to androgenic challenge.

PMID- 8546989
TI  - Irritant susceptibility and weal and flare reactions to bioactive agents in
      atopic dermatitis. II. Influence of season.
AB  - Many atopic dermatitis (AD) patients have exacerbations of their skin disease in
      winter. These exacerbations may be caused by non-immunological 'non-specific'
      factors, such as low sun exposure and low temperature. To date, the influence of
      season on non-specific skin reactivity in AD has not been studied. The aim of the
      present investigation was to assess the influence of season on two skin
      parameters which may be used as quantitative measures of non-specific skin
      reactivity in AD: (i) susceptibility to repeated epicutaneous irritant (sodium
      lauryl sulphate, SLS) exposure, and (ii) weal and flare responses to
      intracutaneous injection of bioactive agents (codeine, FMLP, histamine,
      methacholine, substance P, trypsin). Four of 16 AD patients had dermatitis which
      was more severe in November than in July. Susceptibility to SLS was increased in
      November, both in AD patients and in control subjects. AD patients were more
      susceptible to SLS than control subjects in both July and November. Pre-exposure
      barrier function and skin hydration were reduced in November. The increased
      irritant susceptibility in November may be attributed to reduced barrier
      function, reduced skin hydration, and/or absence of the beneficial effects of
      ultraviolet light on cellular targets beneath the stratum corneum. Flare
      responses to codeine, methacholine, substance P and trypsin were also increased
      in November compared with July, especially in AD patients. However, smaller
      flares were observed in AD patients than in control subjects, in both July and
      November. Flare values were negatively correlated with dermatitis severity,
      probably because of down-regulation. Weal responses did not show a clear seasonal
      variation. Hence, susceptibility to epicutaneous irritants and reactivity to
      intracutaneously injected bioactive agents are parameters which may be used to
      monitor season-dependent changes in non-specific skin reactivity.

PMID- 8546991
TI  - Expression of ICAM-3/CD50 in normal and diseased skin.
AB  - ICAM-3 is a newly recognized adhesion molecule, which is a member of the
      immunoglobulin supergene family of ICAMs, and has been shown to be identical with
      the CD50 antigen. Recent functional studies have shown that ICAM-3 is a ligand
      for LFA-1, and plays an important part in immune reactions. To date, very few
      data exist in the literature concerning its expression in the skin. In the
      present study, we investigated the expression of ICAM-3 in normal skin and in 98
      biopsy specimens of various inflammatory and neoplastic dermatoses. ICAM-3 was
      found to be expressed by epidermal CD1a+ Langerhans cells, by cells of Langerhans
      cell histiocytosis, by T and B lymphocytes infiltrating the dermis in cutaneous
      lymphomas and in a wide spectrum of inflammatory dermatoses. Epidermal
      keratinocytes were consistently negative; endothelial expression of ICAM-3 was
      observed in six of the 98 cases. These results show that ICAM-3 is constitutively
      and widely expressed by cells participating in inflammatory dermatoses (including
      Langerhans cells and T and B lymphocytes), and that it can be, albeit rarely,
      induced on endothelial cells and dermal dendrocytes. These results highlight the
      important part that ICAM-3 may play in cutaneous inflammatory and immune
      reactions.

PMID- 8546992
TI  - Expression pattern of the bullous pemphigoid-180 antigen in normal and neoplastic
      epithelia.
AB  - BP180 is a 180kDa hemidesmosomal protein recognized by bullous pemphigoid (BP)
      and pemphigoid gestationis (PG) autoantibodies. Recent cloning and sequence
      analysis performed by our laboratory have revealed that BP180 is a transmembrane
      protein with a long extracellular collagen-like region. A rabbit polyclonal
      antibody has been generated against a recombinant protein, designated GST-N delta
      1, containing a segment of the BP180 ectodomain. The resulting antiserum, RN
      delta 1A, was shown to specifically react with BP180 on immunoblot, and labelled
      the extracellular region of the epidermal hemidesmosome on immunoelectron
      microscopy. A panel of normal and neoplastic human tissues were analysed by
      indirect immunofluorescence (IF) and RN delta 1A, to determine the distribution
      of BP180. A total of nine basal cell carcinomas (BCCs) and four squamous cell
      carcinomas (SCCs) of the skin were also studied. Intense IF staining was seen
      along the basement membrane zone (BMZ) of the epidermis, hair follicles, and the
      periphery of sebaceous gland lobules. The sebaceous lobules showed more intense
      staining in areas close to the duct. The epithelial BMZ of the following tissues
      also reacted with RN delta 1A: cornea, ocular conjunctiva, buccal mucosa, upper
      oesophagus, placenta (amnion placentum), umbilical cord and transitional
      epithelium of the bladder. The epithelium of the jejunum and ovary failed to
      react with RN delta 1A. Staining of the BCCs and SCCs was variable. Five of six
      nodular BCCs showed some anti-BP180 staining at the tumour-stromal interface,
      although the level of staining was less intense than that observed in the
      overlying normal epidermis. All three morphoeic BCCs analysed in this
      investigation did not show any staining with RN delta 1A. Three of four SCCs
      showed weak staining at the tumour-stromal interface. Thus, the tissue
      distribution of BP180 paralleled that of hemidesmosomes, and expression of this
      protein was found to be decreased or absent in cutaneous neoplasms.

PMID- 8546993
TI  - CDW60, which identifies the acetylated form of GD3 gangliosides, is strongly
      expressed in human basal cell carcinoma.
AB  - The monoclonal antibody UM4D4, assigned to the CDw60 cluster of differentiation,
      identifies an epitope expressed on a subset of normal T cells, some malignant T
      cells, melanocytes, malignant melanoma cells and hyperproliferative psoriatic
      keratinocytes. CDw60 antibodies bind to the acetylated form of GD3 gangliosides.
      These gangliosides have been implicated in the control of cellular proliferation.
      Because the acetylated form of GD3 has been demonstrated in basal cell
      carcinomas, we determined whether the CDw60 epitope was expressed in basal cell
      carcinomas (n = 24) and squamous cell carcinomas (n = 2). Biopsies of these
      tumours were sectioned on a cryostat, and stained with anti-CDw60 using a
      sensitive indirect immunoperoxidase technique. A mean of 74 +/- 4% (mean +/- SEM)
      of the basal cell carcinoma cells expressed CDw60. In contrast, CDw60 expression
      in normal skin was confined to melanocytes and a few scattered keratinocytes at
      the basal cell layer. CDw60 expression in basal cell carcinomas was highly
      upregulated at the tumour front in most of the lesions, whereas the squamous cell
      carcinomas showed uniform CDw60 expression in all areas.

PMID- 8546994
TI  - Increased lysophosphatidylcholine content in lesional psoriatic skin.
AB  - Various cell stimuli occur via activation of phospholipase A2, which hydrolyses
      polyunsaturated fatty acids from the sn-2 position of membrane phospholipids,
      resulting in the formation of polyunsaturated fatty acids and lysophospholipids.
      The level of lysophospholipids is determined by the balance between phospholipase
      A2 activity and the rate of catabolism of the lysophospholipids. One of the
      lysophospholipid classes, lysophosphatidylcholine, has been shown to stimulate
      certain leucocyte activities which are of importance for the induction and
      maintenance of inflammation. In addition, it has been demonstrated that
      phospholipase A2 activity is increased in psoriatic skin. In the present study,
      we analysed the levels of lysophosphatidylcholine, by thin layer chromatography,
      in lesional psoriatic skin, uninvolved psoriatic skin and normal skin. The
      lysophosphatidylcholine content, expressed as mumol lysophosphatidylcholine/mumol
      phosphatidylcholine, was 1.55, 0.21 and 0.12% in lesional psoriatic skin,
      uninvolved psoriatic skin and normal skin, respectively. The level of
      lysophosphatidylcholine was significantly elevated in lesional compared with
      uninvolved psoriatic skin (P = 0.004) and normal skin (P = 0.002). The increased
      lysophosphatidylcholine levels in psoriatic skin indicate that the phospholipase
      A2 activation is not accompanied by a corresponding increase in the activity of
      enzymes catabolizing lysoPC. If present in biologically active concentrations,
      lysophosphatidylcholine may contribute to the induction and maintenance of the
      inflammatory and immunological processes occurring in lesional psoriatic skin.

PMID- 8546995
TI  - Quantifying systemic absorption of topical hydrocortisone in erythroderma.
AB  - The systemic absorption of topical hydrocortisone (HC) was quantified in seven
      patients with erythroderma, using the ratio of the areas under the curves for
      plasma concentration vs. time, following topical and intravenous administration.
      Over a period of 24 h, 19-93 mg of HC was absorbed systemically, corresponding to
      4-19% of the total topical dose of 500 mg. Thus, topical HC therapy of
      erythroderma is accompanied by a pharmacologically significant systemic dose.

PMID- 8546996
TI  - Keratoderma with scleroatrophy of the extremities or sclerotylosis (Huriez
      syndrome): a reappraisal.
AB  - Keratoderma with scleroatrophy of the extremities, also referred to as Huriez
      syndrome, is a rare, autosomal dominant condition, first described in 42 of 132
      members of two families from northern France. The term sclerotylosis was proposed
      because of the pseudosclerodermatous appearance of the hands and digits. The
      distinctive feature of this syndrome is the risk of the development of squamous
      cell carcinoma on affected skin. Since the initial description of this disease,
      three other families, and possibly a fourth, have been reported. In the present
      study, we reassessed the clinical, pathological and genetic data in 114 members
      of one of the two original families, of whom 27 were affected by this syndrome.

PMID- 8546997
TI  - A comparison of twice-weekly MPD-PUVA and three times-weekly skin typing-PUVA
      regimens for the treatment of psoriasis.
AB  - The most frequent PUVA treatment regimen in current use is three times weekly,
      using skin typing to estimate the starting dose. Recently, it was suggested that
      twice-weekly treatment, using the minimal phototoxic dose (MPD) to calculate
      suberythemal starting doses of UVA, achieved similar clearance rates with fewer
      treatments and a lower cumulative UVA dose. We have carried out a trial on 83
      patients, comparing twice-weekly MPD-PUVA with three times-weekly skin typing
      PUVA, in order to test this hypothesis. Although clearance rates were comparable
      between the two regimens, there was no overall significant difference in the
      number of treatments or in the cumulative UVA doses at clearance. However, for
      patients with skin types I and II the cumulative UVA dose was significantly
      higher using the twice-weekly MPD regimen (70.0 J/cm2 vs. 55.8 J/cm2; P < 0.05).
      Our results do not confirm that there is a reduction in cumulative UVA dosage
      with twice-weekly MPD-PUVA.

PMID- 8546998
TI  - Patient-reported morbidity following flashlamp-pumped pulsed tunable dye laser
      treatment of port wine stains.
AB  - Sixty-two patients with port wine stains completed a questionnaire related to
      their flashlamp-pumped pulsed tunable dye laser treatment. The treatment was well
      tolerated by the majority. Forty-eight per cent of patients experienced some
      weeping or crusting after treatment. The major cause of morbidity was protracted
      bruising following treatment, and this caused a significant restriction of
      activities in 45% of patients.

PMID- 8546999
TI  - Inhibition of the metabolism of endogenous retinoic acid as treatment for severe
      psoriasis: an open study with oral liarozole.
AB  - Retinoids derived from retinol or beta-carotene are inactivated, among other
      ways, by enzymes belonging to the P450 cytochrome group. Liarozole, an imidazole
      containing compound, is known to be a potent inhibitor of the cytochrome P450
      mediated metabolism of all-trans retinoic acid. As a result, increased levels of
      this retinoid are found in skin and plasma. Therefore, in the treatment of
      psoriasis, therapeutic effects may be expected with liarozole which are similar
      to those observed with synthetic retinoids. In an open study, oral liarozole was
      given at a daily dose of 75 mg b.i.d., for 12 weeks to 31 patients with severe
      psoriasis. After 1 month, this dosage could be increased to 150 mg b.i.d. if
      there was no improvement or only moderate improvement. Initially, the effect of
      liarozole was mainly on scaling. A decrease in the Psoriasis Area and Severity
      Index (PASI) score of 45% at week 4, of 69% at week 8 and of 77% at week 12 was
      obtained, compared with baseline. A further decrease in the PASI score of up to
      87% was observed in the 16 patients who were allowed to continue treatment for a
      maximum period of 12 months. An excellent or good improvement was noted in 77% of
      the patients within 12 weeks of starting treatment. This response rate had
      increased to 88% by the last follow-up visit. Nearly all patients (29 of 31)
      experienced adverse reactions, such as dry oral mucosa, headache and itching.
      These were mostly mild and transient, but four patients dropped out of the study
      because of an adverse event. Haematological, biochemical and cardiovascular
      parameters were not significantly influenced by liarozole. Six patients showed an
      increase in triglycerides, which normalized in three of four patients during
      further treatment. The results of this pilot study suggest that, at doses of 75
      150 mg b.i.d., liarozole is an active antipsoriatic drug, and may be a useful
      addition to the existing therapeutic armamentarium. Controlled studies should be
      performed to compare liarozole with standard oral treatments.

PMID- 8547000
TI  - An update on pachydermodactyly and a report of three additional cases.
AB  - Pachydermodactyly is a benign condition characterized by symmetrical, painless,
      diffuse swelling of the skin on the lateral aspects of the proximal
      interphalangeal joints of the fingers. Histopathological examination shows
      epidermal hyperplasia, an increase of dermal collagen bundles and a slightly
      increased number of fibroblasts. We report three adolescent males with
      pachydermodactyly. We also review 20 published cases, and discuss the
      differential diagnosis, clearly distinguishing pachydermodactyly from 'true' and
      'false' knuckle pads.

PMID- 8547001
TI  - Necrobiotic xanthogranuloma with cardiac involvement.
AB  - A patient with necrobiotic xanthogranuloma (NXG) and paraproteinaemia, who was
      followed-up for several years, and treated with low-dose chlorambucil, died as a
      result of a respiratory illness. The significant findings at autopsy were a
      xanthogranuloma of the spleen and giant cell myocarditis. The myocardial lesions
      were composed of macrophages, giant cells and lymphocytes. This finding is
      important because four of five known autopsied patients with NXG have had giant
      cell myocardial disease, and an effort at antemortem diagnosis should be made.

PMID- 8547002
TI  - An unusual form of localized papulonodular cutaneous histiocytosis in a 6-month
      old boy.
AB  - We report a 6-month-old boy with an unusual form of cutaneous histiocytosis. The
      lesions were noticed shortly after birth, and there was no evidence of systemic
      disease. This histiocytic disorder could not be classified according to the
      Histiocyte Society classification, and was therefore designated an 'unclassified'
      group II histiocytic disorder. The clinical picture was characterized by dark-red
      papulonodules with a tendency to coalesce into plaques. Histologically, the
      infiltrate was characterized by non-epidermotropic histiocytes showing varying
      degrees of differentiation, eosinophils and lymphocytes, and by the absence of
      foamy cells and Touton giant cells. As a most conspicuous feature, electron
      microscopic examination revealed laminated dense bodies, whereas Birbeck granules
      and comma-shaped bodies were absent. This further distinguished this uncommon
      variant from the well-known class II histiocytoses. During a 6-month follow-up
      period all the lesions showed marked regression.

PMID- 8547003
TI  - Eccrine syringofibroadenoma. Report of a case and immunohistochemical study of
      keratin expression.
AB  - We report a 49-year-old woman with an eccrine syringofibroadenoma. An
      asymptomatic nodule appeared on the right heel, and subsequently enlarged
      gradually. Histological examination revealed anastomosing strands of pale
      epithelial cells, with occasional duct formation and mucinous fibrovascular
      stroma. There were two types of strands: thick and thin. Immunohistochemical
      study, using a panel of monoclonal antikeratin antibodies, revealed that the
      immunoreactivity differed between the two types of strands. The thick strands
      showed a staining pattern similar to the uppermost portion of the intradermal
      duct, and the thin strands showed a pattern similar to the other portion of the
      duct. This observation suggests that the thick and thin strands differentiate
      towards the uppermost portion and the remainder of the duct, respectively.

PMID- 8547004
TI  - Hydroxyurea-induced dermatomyositis-like eruption.
AB  - Hydroxyurea is frequently used to treat myeloproliferative syndromes. Cutaneous
      lesions resembling those seen in dermatomyositis have rarely been reported in the
      course of treatment with hydroxyurea. We report six additional patients with this
      unusual adverse effect. All of the patients had a very typical and similar
      cutaneous eruption, with scaly, linear erythema on the dorsa of the hands. Leg
      ulceration occurred in two cases. Muscle involvement was never observed. One
      patient had unexplained lung disease. In all the others the disorder pursued a
      benign course, even when hydroxyurea was not withdrawn. Dermatomyositis-like
      lesions seem to be a not infrequent and characteristic adverse reaction to
      hydroxyurea. Investigations are not required, and the course is usually benign.

PMID- 8547005
TI  - Aggressive squamous cell carcinomas developing in patients receiving long-term
      azathioprine.
AB  - We report three patients who developed unusually aggressive squamous cell
      carcinomas after receiving long-term azathioprine treatment for dermatological
      disorders. Two patients gave a history suggestive of moderate to excessive sun
      exposure, and the third suffered from chronic actinic dermatitis. Hence,
      ultraviolet light damage may have been a significant cofactor in the development
      of these malignancies. Careful follow-up is necessary in patients who are taking
      azathioprine long term, and who have previously been excessively exposed to
      ultraviolet light (UVL), or in whom future exposure is likely to be excessive. We
      suggest that strict sun avoidance measures are followed by patients on long-term
      azathioprine, or that alternatives to azathioprine therapy are considered,
      especially in individuals inherently at risk of UVL damage, and in those already
      showing clinical signs of such damage.

PMID- 8547007
TI  - Remission of severe epidermolysis bullosa acquisita induced by extracorporeal
      photochemotherapy.
AB  - We report a patient with severe epidermolysis bullosa acquisita (EBA) whose
      disease was refractory to conventional treatments. New bullae continued to
      develop over greater than 50% of his body surface area despite therapy. His
      course was complicated by hyperglycaemia, sepsis, hypoxia caused by pulmonary
      Aspergillus infection and an idiopathic cardiomyopathy. His EBA resolved after
      treatment with extracorporeal photochemotherapy (ECP). Hence, ECP may be
      effective in the treatment of severe EBA which has failed to respond to standard
      treatment regimens.

PMID- 8547006
TI  - Topical 5-fluorouracil in the treatment of Darier's disease.
AB  - Two patients suffering from therapy-resistant Darier's disease were treated with
      topical 5-fluorouracil (5-FU). The drug was applied in a concentration of 1% in a
      cream base, once daily, in left-right comparison with either 7.5% salicylic acid
      in petrolatum or 0.05% vitamin A acid cream. Both patients were on long-term
      treatment with oral retinoids. After 1 week of treatment, a considerable
      improvement was already apparent on the 5-FU-treated side, in comparison with the
      salicylic acid- and vitamin A acid-treated sides. Subsequent treatment of all
      skin lesions with 5-FU for a further 2 weeks resulted in complete clearance of
      the lesions. Remission periods were of 2-6 months duration. There were no
      significant adverse effects of treatment. Haematological parameters remained
      unchanged during the therapy. Topical 5-FU is a safe and useful addition to
      currently available treatments for Darier's disease.

PMID- 8547008
TI  - Mucocutaneous histoplasmosis in AIDS.
AB  - A 36-year-old man, who was an intravenous drug abuser, developed thoracic herpes
      zoster, paronychia, oral candidosis, necrotizing gingivitis and bilateral parotid
      salivary gland swelling. Granulomatous oral lesions and ulceration on the nose
      were shown to be due to disseminated histoplasmosis.

PMID- 8547009
TI  - Acyclovir-resistant chronic cutaneous herpes simplex in Wiskott-Aldrich syndrome.
AB  - A 28-year-old man with Wiskott-Aldrich syndrome presented with ulcerative
      proliferative lesions on his face from which herpes simplex type 1 (HSV-1) was
      isolated. He was initially treated with 10 mg/kg of acyclovir (Zovirax)
      intravenously every 8 h, but his skin lesions worsened. Clinical resistance to
      acyclovir was suspected, and therapy with this drug was intensified. The dosage
      of acyclovir was increased to 45 mg/kg, administered by continuous infusion, and
      the lesions subsequently resolved. The strain of HSV recovered from the patient
      showed acyclovir-resistance in vitro, using the colorimetric method with neutral
      red. Herpes simplex virus resistance to acyclovir is rare. It is more common in
      immunocompromised patients if subtherapeutic doses are administered in the
      treatment of chronic persistent forms of infection. Whenever clinical resistance
      to acyclovir is suspected, the dosage should be increased to 2 mg/kg per h
      administered via an infusion pump. If no improvement is observed in the patient's
      condition with this regimen, a phosphorylated medication whose mechanism of
      action is not dependent on viral thymidine kinase, such as foscarnet
      (phosphonoformic acid), should be substituted.

PMID- 8547011
TI  - Unusual cutaneous manifestations of myelodysplastic syndrome.
AB  - We report a 58-year-old patient with acute myeloid leukaemia who developed an
      oedematous erythema resembling Sweet's syndrome, accompanied by atypical erythema
      nodosum and bullous pyoderma gangrenosum. Examination of skin biopsies showed
      dense infiltration with mature neutrophils, although there was peripheral blood
      leucocytopenia. The oedematous erythema worsened after he was treated with
      granulocyte-colony-stimulating factor (G-CSF), which was given for his
      leucocytopenia. We suggest that when a neutrophilic dermatosis complicates
      leukaemia, alternatives to G-CSF should be considered for the treatment of
      leucocytopenia. Corticosteroids were very effective in controlling the skin
      lesions in our patient.

PMID- 8547010
TI  - Cutaneous protothecosis: report of a case in Hong Kong.
AB  - We report a patient who presented with recalcitrant ulcerated papules and plaques
      on both legs. Histopathology revealed protothecosis, and subsequent culture of
      the lesions grew Prototheca wickerhamii. Gradual resolution of the ulcers
      occurred on treatment with itraconazole.

PMID- 8547012
TI  - A rare presentation of acantholytic dyskeratosis.
AB  - We describe an elderly woman who presented with numerous papular, keratotic
      lesions on the scalp. Histology of a biopsy specimen revealed epidermal
      invaginations, with large keratotic plugs, at the sites of hair follicles. In
      addition, there was acantholytic epidermal cell separation at a suprabasal level,
      and a large number of corps ronds were present above the split. It is likely that
      this case represents a rare presentation of acantholytic dyskeratosis. The
      relationship to other conditions which show acantholysis and dyskeratosis
      histologically is discussed.

PMID- 8547013
TI  - Drug-induced Sweet's syndrome (acute febrile neutrophilic dermatosis) associated
      with hydralazine.
AB  - We report a case of Sweet's syndrome associated with hydralazine. The association
      of Sweet's syndrome with hydralazine, and with the oral contraceptive,
      minocycline, and trimethoprim/sulphamethoxazole, has been reported previously. We
      suggest that a drug aetiology should be sought in cases of Sweet's syndrome.

PMID- 8547014
TI  - Systemic steroids and eczematized Darier's disease.

PMID- 8547015
TI  - Treatment of basal cell papillomas.

PMID- 8547016
TI  - Eruptive acanthomas following sunburn.

PMID- 8547017
TI  - Successful treatment of resistant facial lesions of atopic dermatitis with 0.1%
      FK506 ointment.

PMID- 8547018
TI  - Vitiligo complicating diphencyprone sensitization therapy for alopecia
      universalis.

PMID- 8547019
TI  - Topical 0.05% betamethasone dipropionate: efficacy in psoriasis with once a day
      vs. twice a day application.

PMID- 8547020
TI  - Fordyce spots on the glans penis.

PMID- 8547021
TI  - Dystrophic form of inherited epidermolysis bullosa in a dog (Akita Inu).
AB  - We report a dog with dystrophic epidermolysis bullosa. This 4-year-old female
      Akita Inu, a species of Canis familiaris var. japonicus Temminck, had a 3-year
      history of ulcers and scars over the pressure areas on the limbs, and dystrophic
      nails, since the age of 1 year, which corresponds to early adulthood in humans.
      Electron microscopy of a blister revealed separation beneath the lamina densa,
      and a reduction in the number of anchoring fibrils. The NC-1 domain of type VII
      collagen was positively stained with monoclonal antibody LH7.2 at the basement
      membrane zone. These findings indicate that humans and dogs have a similar
      response to antibody LH7.2, which may aid the development of an animal model for
      this disease.

PMID- 8547022
TI  - Pulsed dye laser treatment in lupus erythematosus telangiectoides.

PMID- 8547023
TI  - Verrucous skin lesions on the feet in diabetic neuropathy.

PMID- 8547024
TI  - Polymyositis, dermatomyositis and malignant melanoma.

PMID- 8547025
TI  - Sunburn and neuropeptide depletion.

PMID- 8547026
TI  - Lindane neurotoxicity.

PMID- 8547027
TI  - Recurrent fixed drug eruption due to clioquinol.

PMID- 8547028
TI  - High-dose intravenous immunoglobulins for immediate control of severe pemphigus
      vulgaris.

PMID- 8547029
TI  - Malignant melanoma appearing in a seborrhoeic keratosis.

PMID- 8547030
TI  - The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell
      alloantigen presentation to CD4+ T cells.
AB  - Intercellular adhesion molecule (ICAM)-3 is a recently described member of the
      immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2.
      All three ICAMS are cognate for the counter-receptor lymphocyte function
      associated antigen-1 (LFA-1, CD11a/CD18). Unlike ICAM-1 and ICAM-2, ICAM-3 is
      constitutively expressed at high levels on resting leucocytes. We investigated
      the expression and function of ICAM-3 in normal skin (n = 5), as well as its
      expression in psoriasis (n = 4), atopic eczema (n = 4), allergic (rhus) contact
      dermatitis (n = 3), and cutaneous T-cell lymphoma (CTCL, n = 2). Five-micrometre
      cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and
      a well characterized immunoperoxidase technique. In normal skin, ICAM-3 was
      expressed by all cutaneous leucocytes but most striking was the strong expression
      of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation
      was confirmed by double-labelling with CD1a and negative staining with an IgG1
      isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and
      CTCL, ICAM-3 was co-expressed on all CD1a+ cells, although, in psoriasis, the
      intensity of ICAM-3 expression was reduced. Functional blocking experiments were
      performed to determine whether the observed ICAM-3 expression on Langerhans cells
      was functionally important in antigen presentation. CD4+ T cells were prepared
      from peripheral blood and 10(5) CD4+ T cells combined with 10(5) epidermal cells
      harvested from keratome biopsies of normal skin of an individual allogeneic to
      the T-cell donor. Addition of 50 micrograms anti-ICAM-3 to the co-culture
      resulted in a consistent (50%) reduction in degree of alloantigen presentation by
      Langerhans cells to T cells. Inhibition was 77% of that produced by the addition
      of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by
      Langerhans cells and is a major ligand for LFA-1 on CD4+ T cells during their
      response to Langerhans cells. Because fresh Langerhans cells constitutively
      express little ICAM-1, whereas ICAM-3 is constitutively expressed at high levels,
      it would appear that ICAM-3 is the dominant functional ICAM on in situ Langerhans
      cells in the normal epidermis.

PMID- 8547031
TI  - Expression of cytokeratins in regenerating human epidermis.
AB  - The expression of cytokeratin polypeptides in regenerating human epidermis was
      immunohistochemically examined during re-epithelization of suction blisters. The
      regenerating basal and suprabasal epidermis expressed keratin polypeptides K13,
      K14, K16 and K18, which are not present in normal suprabasal epidermis. On the
      contrary, K10, a normal constituent of terminally differentiated keratinocytes,
      was lacking from the epidermis until the ninth day of re-epithelization. The
      findings indicate changes similar to other hyperproliferative states (expression
      of K16), basal-like features (expression of K14), or properties reminiscent of
      fetal skin (K13 and K18) in the newly formed epidermis. Monoclonal antibodies for
      cytokeratins and a technique using suction blisters seemed to be a suitable
      methodology for the study of epidermal regeneration in normal skin. The technique
      may also have advantages in the investigation of keratin expression in diseased
      skin.

PMID- 8547032
TI  - Histomorphometric parameters and susceptibility to neutrophil elastase
      degradation of skin elastic fibres from healthy individuals and patients with
      Marfan syndrome, Ehlers-Danlos type IV, and pseudoxanthoma elasticum.
AB  - The morphometric parameters of mid-dermal elastic fibres from the skin of four
      patients with Marfan syndrome, four patients with Ehlers-Danlos syndrome type IV
      (EDS IV), and two patients with pseudoxanthoma elasticum (PXE) were determined,
      and compared with those of healthy individuals of a similar age range. The volume
      fraction occupied by elastic fibres was significantly reduced in Marfan patients
      compared with normal controls, and this was independent of age. In contrast, it
      was significantly increased in PXE patients, whereas the volume fraction occupied
      by skin elastic fibres varied within the EDS IV group. Dermal elastic fibres from
      patients with Marfan syndrome, EDS IV and PXE are hydrolysed by human neutrophil
      elastase in a qualitatively and quantitatively different fashion from those from
      healthy individuals. Marfan syndrome and EDS IV dermal elastic fibres were found
      to be more resistant to hydrolysis by human neutrophil elastase, but PXE elastic
      fibres were hydrolysed at a rate similar to elastic fibres from control skin.

PMID- 8547033
TI  - Keratinocyte conditioned medium stimulates type IV collagenase synthesis in
      cultured human keratinocytes and fibroblasts.
AB  - We have previously shown that conditioned medium from cultured human
      keratinocytes stimulates proliferation of a variety of cell types involved in
      wound healing, as well as re-epithelialization of wounds in human skin in vitro.
      We now present evidence for an autocrine/paracrine control of the synthesis of
      type IV collagenases in human keratinocytes and fibroblasts. During wound
      healing, keratinocytes migrate over the wound bed, an activity coupled with lysis
      of basement membranes, and hence requiring the presence of collagenases.
      Collagenases are also needed for the production and remodelling of the
      granulation tissue. In order to study the autocrine/paracrine control of
      collagenase production in keratinocytes and fibroblasts, we stimulated these
      cells in culture with conditioned medium from cultured keratinocytes. Protease
      synthesis was determined by affinity labelling with 3H
      diisopropylfluorophosphoridate (DFP) and by zymography. Keratinocyte-conditioned
      medium was found to increase the expression of 72 and 92 kDa type IV collagenase
      in human keratinocytes, and the 72 kDa collagenase in human fibroblasts,
      indicating that an autocrine/paracrine control mechanism is involved in
      collagenase production in these cell types during wound healing. This increased
      expression of collagenases could be partly responsible for the stimulated healing
      seen in wounds treated with sheets of cultured keratinocytes.

PMID- 8547034
TI  - The expression of c-erbB-2 protein in the keratinocytes of oral mucosal lichen
      planus.
AB  - The expression of the c-erbB-2 protein was studied in the keratinocytes from
      patients with: (i) oral mucosal lichen planus (OLP) (n = 26); (ii) oral mucosal
      squamous cell carcinoma (OMSCC) which had arisen in mucosa affected by OLP (n =
      5); and (iii) normal oral mucosa (n = 5). C-erbB-2 protein was expressed on the
      cell membranes of the keratinocytes of nucleated epithelium in the stratum
      spinosum. The antigenic determinant recognized represents the cytoplasmic domain
      of a cell surface receptor which binds an as yet uncharacterized heparin binding
      ligand of unknown function. The specimens from the five normal subjects showed
      positive immunohistochemical staining with the monoclonal c-erbB-2 protein
      antibody, the OMSCC specimens were negative, and 23 of 26 of the OLP specimens
      were positive. The lack of c-erbB-2 expression in the three OLP and in the five
      OMSCC specimens may indicate a genetic alteration, or masking of the expression
      of c-erbB-2. The absence of expression in OLP specimens might be an indicator of
      the possibility of future neoplastic transformation.

PMID- 8547035
TI  - Immunohistological comparison of granulated cell proteins in induced immediate
      urticarial dermographism and delayed pressure urticaria lesions.
AB  - Urticarial dermographism and delayed pressure urticaria are two forms of physical
      urticaria which are well defined clinically and histologically. Previous studies
      have shown eosinophil granule protein deposition in urticarial reactions,
      including chronic urticaria, solar urticaria and delayed pressure urticaria. To
      evaluate and compare the involvement of granulated inflammatory cells in
      urticarial dermographism and delayed pressure urticaria, we studied sequential
      biopsies of induced lesions of urticarial dermographism and delayed pressure
      urticaria by indirect immunofluorescence, to detect eosinophil granule major
      basic protein (MBP) and neutrophil granule elastase. Biopsies from dermographic
      lesions at time 0, 5 min, 15 min, 2 h and 24 h, showed few infiltrating
      eosinophils, with minimal extracellular MBP deposition, and a few infiltrating
      neutrophils, with minimal neutrophil elastase deposition, throughout the
      evolution of the lesions. Sequential biopsies of delayed pressure urticaria at
      time 0, 20 min, 6, 12 and 24 h, showed eosinophil infiltration with extensive MBP
      deposition beginning at 20 min, and neutrophil infiltration with variable
      elastase deposition beginning at 20 min. Control tissue specimens from normal
      volunteers showed neutrophil infiltration and slight degranulation, but no
      eosinophil infiltration or degranulation. Comparison of urticarial dermographism
      with delayed pressure urticaria showed marked differences in the patterns of
      infiltration. Delayed pressure urticaria, with eosinophil and neutrophil
      degranulation, was strikingly similar to the IgE-mediated late phase reaction. In
      contrast, eosinophil and neutrophil involvement in urticarial dermographism was
      minimal. Considering the extent of eosinophil granule protein deposition and the
      biological activities of the eosinophil granule proteins, the findings in delayed
      pressure urticaria point to an important pathophysiological role of eosinophils
      in the disease.

PMID- 8547036
TI  - Diversity of immunobiological functions of T-cell lines established from patients
      with adult T-cell leukaemia.
AB  - In order to understand the variety of HTLV-1-associated cutaneous diseases, we
      studied the cytological profile of HTLV-1-infected T-cell lines established from
      patients with adult T-cell leukaemia (ATL). Among four CD4+ cell lines, termed
      16T(-), 35T(-), MH-1, and KS-2, the 16T(-) cells secreted elevated quantities of
      IL-4, IL-6 and IFN-gamma and expressed mRNA for each cytokine in the absence of
      exogenous stimulation. The 35T(-) cells secreted IL-6 and a small amount of IFN
      gamma, but not IL-4. The MH-1 and KS-2 cells secreted only IL-6 in the absence of
      stimulation. In response to stimulation with phorbol-12-myristate-13 acetate
      (PMA), the 16T(-) cells produced more IL-4 and IFN-gamma, whereas the 35T(-) and
      MH-1 cells exhibited increased secretion of IFN-gamma, but still no IL-4 or IL-4
      mRNA production. Although neither IL-4 nor IFN-gamma were found in the culture
      supernatant of KS-2 cells, the production of IL-4 mRNA was detected by RT-PCR.
      Culture supernatants from the 16T(-) and 35T(-) cells induced the expression of
      intercellular adhesion molecule-1 (ICAM-1) and HLA-DR by cultured keratinocytes.
      This response was inhibited by pretreatment of the supernatant with anti-IFN
      gamma antibodies. These results indicate that some HTLV-1-infected T-cell lines
      constitutively secrete various cytokines, including biologically active IFN
      gamma. The diversity of immunobiological functions of the T-cell lines may be
      related to the variety of clinical features present in ATL patients.

PMID- 8547037
TI  - Proliferating cell nuclear antigen distribution in verrucous carcinoma of the
      skin.
AB  - Verrucous carcinoma (VC) of the skin is a rare variety of well-differentiated
      squamous cell carcinoma (SCC) characterized by aggressive local growth and a low
      metastatic potential. These tumours are known to have histological and
      virological features similar to classic warts or condylomata. The aim of the
      present study was to map the proliferative compartment in VC (n = 7) in
      comparison with warts (n = 10) and typical well-differentiated SCC (n = 10). The
      proliferating cells were detected by immunostaining of proliferating cell nuclear
      antigen (PCNA) in formalin-fixed, paraffin-embedded tissue sections, using the
      commercially available anti-PCNA monoclonal antibody PC10. Normal epidermis
      served as a positive control and reference. In VC and warts, the PCNA-positive
      cells were principally located at the periphery of lesions, in the basal layer of
      the tumour islands. In some warts, however, stronger PCNA expressed was noted in
      the superficial layers, of the lesions corresponding to virus-infected
      keratinocytes (koilocytotic cells). In contrast, in SCC, PCNA-positive cells were
      randomly scattered throughout the tumours. Our findings suggest that, on the
      basis of mapping of PCNA distribution, VC resembles large warts or condylomata
      rather than typical SCC. Thus, VC appears to be a distinct clinical entity,
      intermediate between these two types of lesions, not only because of its clinical
      entity, intermediate between these two types of lesions, not only because of its
      clinical and virological features, but also with regard to its proliferative
      organization.

PMID- 8547038
TI  - Expression of the antigen recognized by mAb GB36 in normal skin and in skin
      tumours.
AB  - GB36, a mouse monoclonal antibody (mAb) raised against an epithelial antigen of
      the human trophoblast, reacts with the epithelial basement membrane of chorionic
      villi; it does not react with the invasive extravillous cytotrophoblast.
      Expression and characterization of the antigen of GB36 (designated GBA36) were
      investigated in normal keratinocytes by immunoprecipitation, immunofluorescence
      and immunoelectron microscopic studies. Immunoprecipitation experiments
      demonstrated that the proteins identified on keratinocytes by mAb GB36 and a rat
      mAb anti-integrin alpha 6 (GoH3) were the same. Using immunofluorescence and
      immunoelectron microscopic methods, GBA36 was localized on the cell membrane
      facing the epithelial basal lamina of basal keratinocytes. GBA36 distribution in
      benign and malignant skin tumours was evaluated by immunostaining methods
      (immunofluorescence and immunoperoxidase). Analysis of tumours revealed that
      whereas benign epithelial tumours and intradermal naevi displayed high levels of
      GBA36, the expression of this antigen decreased progressively in spinocellular
      and basal cell carcinomas, and in cutaneous melanomas in relation to
      invasiveness. During cell transformation, GBA36 undergoes quantitative
      alterations, and expression is down-regulated. Although the functional relevance
      of these changes remains unknown, the correlation of decreased GBA36 expression
      with tumour progression may indicate a role for altered integrin expression in
      tissue invasion by human skin carcinoma and melanoma.

PMID- 8547039
TI  - Dopa reaction of fetal melanocytes before and after skin transplantation on to
      nude mice.
AB  - We have previously demonstrated that human fetal epidermal melanocytes are dopa
      negative. The present study was conducted to test the hypothesis that human fetal
      melanocytes can be activated to produce melanin under conditions differing from
      their natural in utero environment. To address this question, dopa staining
      activity of fetal epidermal sheets, obtained from seven aborted fetuses with
      estimated gestational ages of 13-20 weeks, was evaluated before and after
      engraftment on to nude mice. Dopa staining became positive 7 days post
      engraftment. The intensity of the dopa reaction and the mean number of
      melanocytes increased by day 14 post-engraftment, and these changes were even
      greater by day 30. These observations indicate that human fetal melanocytes,
      potentially capable of synthesizing melanin under conditions differing from their
      normal in utero environment, are either inhibited, or not stimulated to do so.

PMID- 8547040
TI  - Immunohistochemical expression of retinoblastoma protein in cutaneous melanomas.
AB  - Retinoblastoma protein (pRB) is the product of a tumour-suppressor gene (rb)
      mapped to chromosome 13q14. pRB acts as a control checkpoint at the G1 phase of
      the cell cycle, preventing cells from entering into the S phase. Mutational
      inactivation of both normal alleles leads to loss of pRB expression and the
      development of malignant neoplasms. Absence of pRB occurs in retinoblastomas,
      sarcomas and several other types of tumours. The potential role of pRB in the
      pathogenesis of cutaneous melanoma is unknown, and was the subject of this
      investigation. Formalin-fixed, paraffin-embedded sections of four cutaneous
      melanoma metastases, 17 primary invasive melanomas and 10 predominantly
      intradermal melanocytic naevi were studied. Monoclonal antibodies directed
      against pRB and Ki-67 antigen were used after microwave heating of sections to
      restore antigenicity. pRB was not detected in morphologically normal epidermal
      melanocytes. In five naevi, only scattered cells (1%) expressed pRB, whereas in
      the other five naevi, pRB expression was undetectable. In contrast, pRB was
      detected in all primary and metastatic melanomas (5-70% of cells). Expression was
      always localized to nuclei. Ki-67 expression was detected only in the melanomas,
      with both cellular staining and regional localization similar to that shown by
      pRB in 13 of the 20 melanomas studied with both antibodies. pRB appears to be
      expressed at higher levels in melanomas than in benign naevi. It therefore seems
      unlikely that loss of rb expression is an important factor in the pathogenesis of
      melanoma.

PMID- 8547041
TI  - Increased lymphocyte infiltration in duodenal mucosa from patients with psoriasis
      and serum IgA antibodies to gliadin.
AB  - In a screening study concerning IgA and IgG antibodies to gliadin (IgA AGA and
      IgG AGA, respectively) in psoriasis, raised levels of IgA and AGA were found to
      be more common than in a reference group. To determine whether elevated AGA
      levels were associated with an increased number of intraepithelial lymphocytes,
      33 patients with IgA AGA (n = 28) or IgG AGA (n = 5) values above 90% of the
      reference values (> 50 units/ml IgA AGA and < 12 units/ml IgG AGA) underwent
      gastroduodenoscopy and duodenal biopsy in a prospective study. For comparison,
      six patients with low levels of both IgA AGA and IgG AGA were included. Five
      biopsy specimens were taken in each patient. Paraffin-embedded specimens were
      examined with regard to the degree of intraepithelial lymphocyte infiltration,
      and scored from 0 to 3. Biopsy specimens with a score of 0 had one mononuclear
      cell or less per four epithelial cells. The specimens were also examined with
      regard to the presence of intraepithelial CD3+ T lymphocytes and gamma/delta+ T
      lymphocytes. In the six patients with low IgA AGA and low IgG AGA, the biopsy
      score was 0. Fourteen of the 33 patients with raised AGA had a score of > or = 1;
      of these, 12 had raised IgA AGA and two had slightly raised IgG AGA. Two of the
      patients with raised IgA AGA had partial villous atrophy, but the majority had
      normal villous architecture. There was a significant correlation both between the
      biopsy score and the number of intraepithelial CD3+ cells and between the score
      and the number of intraepithelial gamma/delta+ positive T lymphocytes. The serum
      IgA AGA levels were significantly correlated with the duodenal biopsy score, the
      number of intraepithelial gamma/delta+ T lymphocytes, and the number of CD3+
      intraepithelial T lymphocytes. Most patients had no, or only mild,
      gastrointestinal symptoms. Of the 14 patients with biopsy scores > or = 1, seven
      had severe psoriasis and five moderately severe psoriasis, whereas only two had
      mild psoriasis. There was no relationship between the duodenal score and
      haemoglobin, folate, whole blood selenium or serum zinc levels. Some of these
      patients improve on a gluten-free diet, but it is still too early to draw any
      definite conclusions concerning the type of relationship between the skin
      lesions, the increased number of intraepithelial lymphocytes in the duodenal
      mucosa and gluten hypersensitivity.

PMID- 8547042
TI  - Systemic high-dose ranitidine in the treatment of psoriasis: an open prospective
      clinical trial.
AB  - We report the results of an open, prospective study on the efficacy of systemic
      ranitidine in the treatment of psoriasis. Twenty patients suffering from moderate
      to severe psoriasis were included in the study. The median pretreatment PASI
      score was 15.7 (range 6.0-24.7). The patients were treated with oral ranitidine
      300 mg twice a day for 6 months; no other medication was allowed during the study
      period. Eighteen patients completed the study. The median PASI score was reduced
      from 15.7 to 14.5, 9.1 and 5.7, after 1, 3 and 6 months of treatment,
      respectively (P < 0.00001). A significant reduction in PASI score was evident at
      3 months of treatment. A mild to moderate deterioration occurred in 15 patients
      within the first month of treatment, but this was followed by improvement during
      prolonged treatment in most patients. No other clinical and/or biochemical side
      effects were observed. Eight patients continued therapy with ranitidine after the
      study was completed, and none of these patients relapsed during a follow-up
      period of 12-18 months. The results of the present study suggest that ranitidine
      may be a beneficial and safe treatment for psoriasis. In addition, high-dose,
      long-term ranitidine treatment appears to be free from severe adverse effects.

PMID- 8547043
TI  - Laser treatment of psoriasis.
AB  - In psoriasis, the earliest observable electron microscopic changes are in the
      dermal papillary vasculature. The flashlamp-pumped pulsed tunable dye laser can
      achieve selective photothermolysis of the dermal vasculature. This laser was used
      to treat eight patients with chronic plaque psoriasis, as it was hypothesized
      that the ablation of dermal papillary vasculature would arrest the early events
      leading to the evolution of psoriasis, and produce resolution of the plaques. At
      the final assessment, performed 10 weeks after three fortnightly laser
      treatments, five of the eight patients recorded an improvement of > or = 50%, and
      one showed complete resolution of the treated plaques of psoriasis. Although not
      practicable in the treatment of widespread psoriasis, we conclude that selective
      photothermolysis of the dermal vasculature by pulsed tunable dye laser offers an
      alternative new therapy for chronic plaque psoriasis, and also demonstrates the
      pivotal role of the vasculature in the pathogenesis of psoriasis.

PMID- 8547044
TI  - PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10
      years' experience at St John's Institute of Dermatology.
AB  - Our 10-year experience with PUVA treatment for alopecia areata, partialis,
      totalis and universalis was retrospectively reviewed using charts and follow-up
      questionnaires for 70 patients at St John's Institute of Dermatology. In all
      cases, several previous therapies were judged to be unsatisfactory prior to
      starting PUVA, and many cases were already deemed clinically refractory prior to
      referral for PUVA. If cases of vellus hair growth are excluded, and those who
      lost their PUVA-induced regrowth rapidly on follow-up, the effective success rate
      was at best 6.3% for alopecia areata partialis, 12.5% for alopecia areata totalis
      and 13.3% for alopecia areata universalis. We affirm that PUVA is generally not
      an effective treatment for alopecia areata.

PMID- 8547045
TI  - Calculation of 8-methoxypsoralen dose according to body surface area in PUVA
      treatment.
AB  - In 41 patients about to start PUVA, the dose of 8-methoxypsoralen (8-MOP) was
      calculated conventionally according to body weight (0.6 mg/kg), or according to
      body surface area (25 mg/m2) predicted from height and weight measurements. The
      two different methods of dosing were used on consecutive treatment days and the
      plasma 8-MOP concentration was measured on each occasion 2 h after ingestion of
      the crystalline form of 8-MOP, given to the nearest 10 mg. Body weight calculated
      doses ranged from 30 to 60 mg with a significant difference in the plasma 8-MOP
      concentration between the dose groups, indicating a systematic variation
      according to the weight of the patient. When calculated according to body surface
      area, only two doses were used (40 or 50 mg), and there was no significant
      difference in plasma 8-MOP concentration between the groups. Calculation of the
      dose of 8-MOP using body surface area may be performed quickly and simply
      provided the height and weight of individual patients is known. We provide
      evidence that this method of dosing will improve the therapeutic effect of PUVA
      in psoriasis.

PMID- 8547046
TI  - Topical isotretinoin in Darier's disease.
AB  - Topical 0.05% isotretinoin (Isotrex gel) was used to treat a test patch of skin
      in 11 patients with Darier's disease. Hyperkeratosis and papules improved in six
      patients after treatment for 3 months. Erythema, burning and irritation were
      common adverse effects, and these were severe in three patients, one of whom
      stopped treatment. Patients with mild Darier's disease may find topical
      isotretinoin helpful, but it is likely that most patients with widespread disease
      will require treatment with systemic retinoids.

PMID- 8547047
TI  - The emergence of Trichophyton tonsurans tinea capitis in Birmingham, U.K.
AB  - The anthropophilic fungus Trichophyton tonsurans is a cause of tinea capitis in
      children. Since the 1950s the organism has spread from Central to North America.
      A similar recent emergence of T. tonsurans has not been reported previously in
      the U.K. T. tonsurans was found to have become the predominant cause of tinea
      capitis in Birmingham, U.K., accounting for 72% of infections investigated in
      1993. The symptoms and signs of the infection were variable and accurate
      diagnosis may be initially difficult. It is, thus, important to be aware of the
      emergence of T. tonsurans in the U.K., so that an early diagnosis can be made to
      facilitate appropriate treatment and to prevent spread of infection to close
      contacts.

PMID- 8547048
TI  - Early events in the invasion of the human nail plate by Trichophyton
      mentagrophytes.
AB  - A new in vitro model for the study of nail invasion by dermatophyte fungi was
      developed. The dermatophyte Trichophyton mentagrophytes, and fragments of finger
      nails and toe-nails were used. Arthroconidia were inoculated on the ventral
      surface of the nails. After 6 h, adherence and germination of arthroconidia was
      observed. By 16 h, small germ tubes with side branches were evident. At about 24
      h, micro-colonies had become established. At 48 h, a mycelium had formed, and at
      about 72 h most of the nail fragment was covered with fungal growth. Nail
      penetration occurred from the ventral surface through the intercellular spaces,
      and with longer incubation all three layers were invaded by arthroconidia growing
      through channels. Nail invasion occurred in the absence of added nutrients.
      Dermatophyte fungi appeared to invade the nail by a combination of mechanical and
      chemical factors. The model provides a substrate to study the pharmacokinetics
      and bioavailability of new antifungal agents in situ.

PMID- 8547049
TI  - A protocol for recording the sign of flexural dermatitis in children.
AB  - The presence of visible flexural dermatitis is a key feature in diagnosing atopic
      dermatitis. We describe a protocol for recording this sign in population-based
      studies, which could be used by suitably trained non-dermatologists. The protocol
      was developed using a standard set of photographs and accompanying instructions,
      which define the terms 'dermatitis' and 'flexural'. When assessed during a survey
      of skin disease in primary schoolchildren, there was excellent agreement between
      a trained nurse and a dermatologist with regard to the presence or absence of
      this sign in 73 consecutive children, with perfect agreement in 71 children
      (97%), and a chance corrected agreement index (kappa statistic) of 0.90 (95%
      confidence interval [CI] 0.77-0.99). Agreement between two nurses on 114
      consecutive schoolchildren was not quite as good, with perfect agreement in 102
      children (90%), and a kappa value of 0.51 (95% CI 0.26-0.77). The protocol is
      easy to perform, does not require children to undress, takes < 1 min to carry
      out, and is highly acceptable to children and staff. This protocol may be useful
      in standardizing the assessment of atopic dermatitis in population studies of
      children.

PMID- 8547050
TI  - Are most primary cutaneous B-cell lymphomas 'marginal cell lymphomas'?

PMID- 8547051
TI  - Satisfactory remission achieved by PUVA therapy in a case of crisis-type adult T
      cell leukaemia/lymphoma with generalized cutaneous leukaemic cell infiltration.
AB  - We used PUVA therapy in a patient with crisis-type adult T-cell
      leukaemia/lymphoma and generalized cutaneous leukaemic cell infiltration. PUVA
      proved very effective in reducing leukaemic cells and in clearing the eruption.
      To understand the way in which PUVA produced a reduction in the number of
      leukaemic cells, we examined peripheral blood cells by light and electron
      microscopy. Light microscopy was of little help, but electron microscopy revealed
      that PUVA induced apoptosis-like changes in circulating leukaemic cells. This
      suggests that apoptosis-like changes in leukaemic cells might be the reason for
      the success of this treatment.

PMID- 8547052
TI  - Diffuse plane xanthomatosis associated with a monoclonal band displaying anti
      smooth muscle antibody activity.
AB  - We report a patient with diffuse planar xanthomatous lesions associated with a
      benign monoclonal gammopathy. This patient has a very high titre of anti-smooth
      muscle antibody (1:10,240), but normal liver function tests and a normal liver
      biopsy. The paraprotein band displays anti-smooth muscle antibody activity. There
      is no evidence of any other underlying disease process. The findings are
      consistent with a diagnosis of diffuse plane xanthomatosis, but the mechanism of
      xanthoma formation remains unclear.

PMID- 8547053
TI  - Erythrodermic bullous pemphigoid is a clinical variant of bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin. Several
      variants of BP have been described but until recently the relationship of these
      variants to generalized BP was unclear. Several studies have shown that
      pemphigoid nodularis, pemphigoid vegetans, localized BP and vesicular pemphigoid
      are true variants of BP as the circulating antibodies in these patients recognize
      the same 230 kDa BP antigen as found in patients with generalized BP.
      Erythrodermic BP is a very unusual variant characterized by an erythroderma along
      with blister formation. We describe the third known patient to develop
      erythrodermic BP and characterize the antigenic specificity of the circulating
      antibodies in both our newly reported patient with erythrodermic BP and in one of
      the two other previously reported cases of erythrodermic BP. Both patients with
      erythrodermic BP had circulating IgG antibodies which bound to the epidermal side
      of salt-split human skin in a pattern identical to two patients with
      immunopathologically proven generalized BP. Sera from four erythrodermic patients
      without blisters and from a healthy normal volunteer, as controls, failed to
      demonstrate detectable circulating IgF autoantibodies. Immunoprecipitation
      studies revealed that both patients with erythrodermic BP had circulating IgG
      autoantibodies which recognized, to varying degrees, the same 230 and 180 kDa BP
      antigens as recognized by sera from two patients with immunopathologically proven
      generalized BP. Sera from four erythrodermic patients without blisters and from a
      healthy normal volunteer, as controls, failed to recognize any specific
      polypeptides. These observations demonstrate that erythrodermic BP is a distinct
      clinical variant of BP.

PMID- 8547055
TI  - Necrotizing herpes zoster mimicking relapse of vasculitis in angioimmunoblastic
      lymphadenopathy with dysproteinaemia.
AB  - An 81-year-old man presented with a generalized maculopapular rash,
      lymphadenopathy, conjunctivitis and arthritis. Vasculitis was confirmed by skin
      biopsy and by direct immunofluorescence, which showed perivascular C3 and
      granular IgM accumulation. Histology of an inguinal lymph node was diagnostic for
      angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), and this was
      confirmed by the finding of hypergammaglobulinaemia and elevated IgE levels.
      Immunohistology on a lymph node biopsy showed a T-helper cell (CD4) infiltrate
      expressing the interleukin (IL)-2 receptor alpha and beta chains. While receiving
      prednisone 100 mg/day, the patient developed new lesions, mimicking a relapse of
      vasculitis, which were subsequently shown to be necrotizing herpes zoster. Serum
      IL-2 and IL-6 levels were elevated. To our knowledge, this is the first report of
      simultaneous elevation of IL-2 and IL-6 in AILD: IL-2 may be involved in
      proliferation of the malignant cell clone, and IL-6 in the pathogenesis of both
      the vasculitis (via endothelial cell activation) and the hypergammaglobulinaemia.

PMID- 8547054
TI  - Pyoderma gangrenosum and cranial osteolysis: case report and review of the
      paediatric literature.
AB  - Pyoderma gangrenosum is a poorly understood, ulcerating cutaneous disorder which
      is rarely seen in the paediatric age-group. We report a 3-year-old boy who
      developed an ulcer over the left frontoparietal scalp at the age of 1 year. A 9
      cm area of underlying cranial bone was destroyed. The appearance on radiographs
      and CT scan was suggestive of eosinophilic granuloma, osteomyelitis, or other
      destructive processes. Biopsies of the scalp lesion and calvaria showed
      granulation tissue and degenerating bone. After the biopsies the scalp lesion
      increased in size, and wound dehiscence occurred. Ulceration developed at the
      site of a PPD skin test, which on biopsy was consistent with the diagnosis of
      pyoderma gangrenosum. Pyoderma gangrenosum should be added to the differential
      diagnosis of cutaneous disorders which can result in osteolytic/osteonecrotic
      defects.

PMID- 8547056
TI  - Bacillary angiomatosis in HIV-infected patients: report of three cases with
      different clinical courses and identification of Rochalimaea quintana as the
      aetiological agent.
AB  - Three cases of cutaneous bacillary angiomatosis in HIV-infected patients are
      reported. They differed profoundly with respect to the extent of the lesions and
      the clinical course. In two cases, Rochalimaea quintana was identified by direct
      sequencing of the DNA amplified with the polymerase chain reaction (PCR), whereas
      an easy, rapid method based on the restriction length of polymorphism analysis of
      PCR products (PCR-RFLP) was used in the third case. This report illustrates the
      variations in clinical presentations and evolutive profiles in patients with
      bacillary angiomatosis, and confirms the causal role of R. quintana in this
      disease.

PMID- 8547057
TI  - Pityriasis rubra pilaris and human immunodeficiency virus infection.
AB  - Recently, the occurrence of pityriasis rubra pilaris (PRP) has been reported in
      patients with HIV infection. It presents different clinical features, and has a
      poorer prognosis, than the classical adult type of PRP. We report the occurrence
      of severe PRP in an HIV-infected patient, and review the previously reported
      cases of this association. We propose the designation of a new category of PRP
      (type 6), characterized by the presence of HIV infection, usually without
      immunosuppression, a poor prognosis and response to treatment, and the
      development of nodulocystic and lichen spinulosus lesions.

PMID- 8547058
TI  - Aplasia cutis congenita after exposure to methimazole: a causal relationship?
AB  - We report a child with scalp aplasia cutis congenita, whose mother was treated
      with methimazole during pregnancy. The relationship between antithyroid drug
      administration during pregnancy and the occurrence of scalp defects is discussed,
      and the pertinent literature is reviewed.

PMID- 8547059
TI  - Focal dermal hypoplasia (Goltz syndrome) associated with multiple giant
      papillomas.
AB  - We report a case of focal dermal hypoplasia (FDH) with multiple giant papillomas
      on nonperimucosal areas. The patient had had cribriform hyperpigmented and
      depigmented plaques on the trunk and extremities since birth. There were also
      hypoplastic skin lesions on the right arm, left elbow and right thigh. The
      multiple giant papillomas began to appear, when she was 22 years old, on the
      trunk and extremities. Cryotherapy was effective in controlling them.

PMID- 8547060
TI  - Novel treatment options in the severe beta-globin disorders.

PMID- 8547061
TI  - Homologous restriction of complement-mediated cell lysis can be markedly enhanced
      by blocking decay-accelerating factor.
AB  - Regulation of complement (C') dependent lysis of cells is attributed to certain
      membrane proteins. One of these is decay-accelerating factor (DAF), CD55, a 70kD
      glycosylated protein which functions to protect host cells from damage by
      autologous C'. We hypothesized that blockade of DAF function by a monoclonal
      antibody (mAb) could augment C'-dependent lysis mediated by another mAb to a cell
      surface antigen expressed on leukaemia cells. Thus, we tested the effects of the
      anti-DAF mAb 1C6 on the ability of both rabbit and human C' to lyse human
      leukaemia cells through activation by complement-fixing murine mAb. DAF antigen
      was highly expressed on most leukaemia cell lines and primary acute leukaemia
      blast cells tested. Murine mAb to CD15 (PM-81) and to gp 120 (AML-1-99), both
      IgM, also bound to the majority of myeloid and lymphoid leukaemia cells. Using
      human serum as a source of C', the addition of mAb 1C6 reduced by an additional
      85-94% the numbers of clonogenic HL-60 (myeloid leukaemia) cells lysed by mAb PM
      81 alone. Similarly, the addition of mAb 1C6 reduced by an additional 87% the
      numbers of HL-60 colonies eliminated by mAb AML-1-99 alone. Similar results were
      observed in an experimental purging model using the myeloid leukaemia cell lines
      HL-60, U937 or NB4 cells as targets. These results show that mAb 1C6 can
      effectively block the actions of DAF. In the presence of mAb 1C6, the cytotoxic
      activity mediated by human C' was similar to that of rabbit C'. These results
      show that increased tumour cell killing can be achieved through DAF blockade.
      This finding has relevance to clinical trials using C'-fixing mAb for purging
      bone marrow of occult tumour cells prior to autologous transplantation.

PMID- 8547062
TI  - VLA-4 and VCAM-1 are the principal adhesion molecules involved in the interaction
      between blast colony-forming cells and bone marrow stromal cells.
AB  - The molecular basis and functional significance of interactions between
      haemopoietic progenitor cells and the stromal microenvironment is still poorly
      understood. Here we investigated a broad panel of surface adhesion molecules for
      their involvement. For this purpose, the colony-forming capacity of stroma
      adherent Bl-CEC, BFU-E and GM-CFC was studied. Both mononuclear bone marrow cells
      (BMC) and bone marrow-derived stromal cells (BMSC) express a wide variety of
      adhesion molecules. However, only antibodies against beta 1-, alpha 4-integrin
      (both chains of the very late activation antigen-4 (VLA-4)) and vascular cell
      adhesion molecule (VCAM-1) inhibited colony formation from stroma-adherent Bl-CFC
      by 50% or more. Antibodies against a panel of other adhesion molecules, including
      the alpha 5-integrin chain, were without effect. Subsequent pretreatment
      experiments revealed that VLA-4 on progenitors interacted with stromal VCAM-1.
      The inhibitory antibodies did not interfere with the clonogenic capacity of but
      with adhesion of BFU-E and GM-CFC. Whether the inhibitory antibodies act
      similarly on progenitors which depend on BMSC for growth and/or differentiation,
      such as BI-CFC, remains to be determined.

PMID- 8547063
TI  - Recombinant PDGF enhances megakaryocytopoiesis in vitro.
AB  - The effect of recombinant platelet-derived growth factor (PDGF) on both murine
      and human megakaryocyte colony formation was studied in the plasma clot culture
      system. PDGF significantly stimulates megakaryocyte colony formation in a dose
      dependent manner. The minimum concentration which had a significant stimulating
      effect on colony forming unit megakaryocyte (CFU-MK) was 10 ng/ml and maximum
      stimulation occurred at 50 ng/ml. The effect of PDGF was compared with that of
      interleukin (IL)-3, IL-6, granulocyte-macrophage colony stimulating factor (GM
      CSF), erythropoietin (EPO) and acid fibroblast growth factor (aFGF) on
      megakaryocyte colony formation. The results showed that megakaryocyte colony
      stimulating activity of PDGF was slightly higher than those of GM-CSF and aFGF,
      but lower than those of IL-3, IL-6 and EPO. The effect of PDGF in combination
      with IL-3 or IL-6 on megakaryocyte colony formation was also investigated. No
      synergistic action was found between PDGF and IL-3 or IL-6, but an additive
      effect was observed with IL-3 plus IL-6. We also studied the effects of PDGF in
      combination with anti-IL6, anti-IL-3 or anti-GM-CSF antibody. The increase of
      megakaryocyte colony formation induced by PDGF was partially inhibited by anti-IL
      6 or anti-GM-CSF antibody but not by anti-IL-3 antibody. These results indicate
      that PDGF is a positive regulator for megakaryocytopoiesis in vitro and IL-6 and
      GM-CSF may play a role in the mechanism whereby PDGF stimulates
      megakaryocytopoiesis.

PMID- 8547064
TI  - The CD4 receptor plays essential but distinct roles in HIV-1 infection and
      induction of apoptosis in primary bone marrow GPIIb/IIIa+ megakaryocytes and the
      HEL cell line.
AB  - We investigated whether cells belonging to the megakaryocytic lineage could be
      infected in vitro with human immunodeficiency virus type-1 (HIV-1). Primary
      GPIIb/IIIa+ bone marrow (BM) cells and HEL continuous cell line were first
      phenotypically characterized for the presence of megakaryocytic markers and CD4
      antigen, then challenged in vitro with the laboratory strain IIIB of HIV-1. Both
      GPIIb/IIIa+ BM and HEL cells expressed significant levels of CD4 receptor (> 50%)
      and were efficiently infected with HIV-1, as judged by the presence of proviral
      DNA after polymerase chain reaction analysis and by quantitative evaluation of
      gag p24 antigen in the culture supernatants. Of note, infection with HIV-1 in
      both primary BM megakaryocytes and HEL cells was specifically blocked by soluble
      recombinant CD4. To ascertain whether the CD4 receptor was essential for
      infection of megakaryocytic cells, HEL were subcloned into CD4+ and CD4- cells.
      Although unfractionated and CD4+ HEL cells were productively infected with HIV-1,
      CD4- HEL cells could not be infected. Infection of HEL cells did not induce gross
      cytotoxic effects or a significant increase of apoptosis. On the other hand,
      treatment of unfractionated or CD4+ HEL cells with cross-linked recombinant env
      gp120 or Leu3a anti-CD4 monoclonal antibody markedly (P < 0.01) increased the
      degree of apoptosis with respect to HEL cells infected with HIV-1 or treated with
      cross-linked gag p24 or anti-GPIIb/IIIa antibody. Taken together, these data
      indicate that the CD4 receptor represents the main route of infection in cells
      belonging to the megakaryocytic lineage. Moreover, an inappropriate engagement of
      CD4 by either free env gp120 or anti-CD4 monoclonal antibody could be more
      relevant than a direct infection with HIV-1 in the induction of the frequent BM
      megakaryocyte abnormalities found in HIV-1 seropositive thrombocytopenic
      patients.

PMID- 8547065
TI  - Effect of interleukin-3 pretreatment on granulocyte/macrophage colony-stimulating
      factor induced mobilization of circulating haemopoietic progenitor cells.
AB  - Recombinant human colony stimulating factors (CSFs) as single agents are
      increasingly used for mobilizing peripheral blood progenitor cells (PBPCs) for
      stem cell transplantation. We have shown in rhesus monkeys that interleukin-3 (IL
      3) pretreatment markedly potentiated the increase in PBPC numbers of subsequent
      administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect
      of IL-3 pretreatment on GM-CSF-induced mobilization of PB progenitors in patients
      who were potential candidates for autologous stem cell transplantation (n = 16).
      Patients were treated with GM-CSF at a dose of 5 micrograms/kg/d for 5 d and
      after a treatment free interval received another cycle of GM-CSF immediately
      following pretreatment with IL-3 at different doses and duration: 2.5
      micrograms/kg/d (n = 4), 5 micrograms/kg/d (n = 3) and 10 micrograms/kg/d (n = 3)
      for 3 d, 5 micrograms/kg/d for 7 d (n = 4) and 5 micrograms/kg/d for 14 d (n =
      2), respectively. Only 7 d pretreatment with IL-3 showed consistent effects.
      Although IL-3 did not mobilize by itself, pretreatment with 5 micrograms/kg/d of
      IL-3 for 7 d significantly potentiated GM-CSF-induced mobilization of PB CFU-GM
      numbers, leading to a mean increase in PB CFU-GM numbers over baseline by 18.5 +/
      5.2 (SEM) fold by IL-3/GM-CSF as compared to a 4.7 +/- 1.7-fold increase by GM
      CSF alone. A significant enhancement by the 7 d IL-3 pretreatment was also
      observed for erythroid (BFU-E) and multipotential progenitor cells (CFU-mix)
      which were 3.3 +/- 1.3- and 3.4 +/- 0.9-fold, respectively, mobilized by GM-CSF
      alone, as compared to 8.5 +/- 2.3- and 19.2 +/- 3.4-fold, respectively, by the IL
      3/GM-CSF combination. Our results suggest that 7 d pretreatment with IL-3 may be
      a useful mean to augment mobilization of circulating progenitors by more lineage
      restricted CSFs. These findings may be important for the design of mobilization
      strategies that use growth factors without preceding chemotherapy.

PMID- 8547066
TI  - Recombinant human interleukin-3 in refractory severe aplastic anaemia: a phase
      I/II trial.
AB  - In a prospective open-labelled phase I/II trial we tested efficacy and
      tolerability of recombinant human interleukin-3 (rhIL-3) alone in patients with
      refractory severe aplastic anaemia (SAA). 15 patients with idiopathic (12
      patients) or secondary (one post-hepatitic, one drug induced, one dyskeratosis
      congenita) SAA, refractory or relapsing after one to three courses of
      antilymphocyte globulin were included. 14 patients were transfusion dependent
      (RBC 14, platelet 12). RhIL-3 was planned for three patients each at five
      escalating dose levels of 1, 2, 4, 8 and 16 micrograms/kg, given daily as 24 h
      continuous infusion for 21 d. RhIL-3 was prematurely withdrawn at days 10 and 11
      for adverse events in two patients. 9/15 patients showed an increase in WBC; 2/6
      at the 1-2 micrograms/kg and 7/9 at the 4-16 micrograms/kg level, but no
      sustained effects were seen. No patient showed a response in platelet counts.
      Additionally, platelet and RBC transfusion requirements were unchanged pre and
      post study. All patients experienced one or more adverse event, mainly fever (15
      patients), bleeding (nine patients), and headache (six patients). Occurrence of
      adverse events was dose related and the maximum tolerated dose was reached with 8
      micrograms/kg. Five patients suffered serious adverse events. RhIL-3 as single
      growth factor and used alone is of minimal benefit in severe aplastic anaemia.

PMID- 8547067
TI  - Is there a role for interleukin-3 in Diamond-Blackfan anaemia? Results of a
      European multicentre study.
AB  - Forty patients (nine adults aged 20-54; 31 children aged 1-17) with Diamond
      Blackfan anaemia (DBA) were treated with recombinant human interleukin-3 (IL-3)
      in a European multicentre compassionate-need study. IL-3 was given as a daily
      subcutaneous injection at a starting dose of 2.5 micrograms/kg, escalating at day
      21 to 5 micrograms/kg, and then to 10 micrograms/kg if there was no response, for
      a total duration of 12 weeks. Three children achieved a significant response,
      achieving sustained remissions off all therapy. At the time of entry, one was
      steroid-responsive and transfusion-independent, and two were transfusion
      dependent. Two adults had a transient reduction in transfusion requirements, but
      could not tolerate the complete course of therapy. Eosinophilia was common;
      neutrophil and platelet counts were unaffected except in three patients in whom
      previously noted mild thrombocytopenia was transiently exacerbated. Clinical
      response to IL-3 did not correlate with in vitro culture results. A comparison of
      individual patient characteristics of our study with previously reported series
      confirms earlier impressions that patients who have never achieved significant in
      vivo erythropoiesis in response to steroids or during a spontaneous remission are
      highly unlikely to respond to IL-3. In contrast, there may be a 50% chance of a
      sustained remission, off steroids, in children who are steroid-dependent and
      transfusion-independent at the time of IL-3 therapy, suggesting a possible role
      for a short course of IL-3 earlier in the treatment of children with steroid
      responsive DBA.

PMID- 8547068
TI  - Interleukin-11 (IL-11) acts as a synergistic factor for the proliferation of
      human myeloid leukaemic cells.
AB  - Interleukin-11 is a stromal cells derived cytokine which stimulates the
      proliferation of primitive haemopoietic progenitor cells. For this paper we have
      studied the constitutive expression of IL-11 mRNA in a panel of wellknown
      leukaemic cell lines and samples from AML patients at diagnosis. Moreover, the
      same cellular populations were evaluated for their proliferative response to
      recombinant-human-(r-hu). IL-11 alone and combined with r-hu-IL-3, granulocyte
      macrophage colony stimulating factor (GM-CSF) and stem cell factor (SCF, c-kit
      ligand). The colony-forming ability of HL60, K562, KG1 cells and eight fresh AML
      cell populations was assessed by a clonogenic assay in methylcellulose. In eight
      additional AML cases the number of S-phase leukaemic cells induced by IL-11 was
      determined by the bromodeoxyuridine (BRDU) incorporation assay after 3d of liquid
      culture. IL-11, as single cytokine, did not stimulate the colony formation of the
      three myeloid cell lines under serum-containing and serum-free conditions. In
      contrast, the proliferation of the leukaemic cells in response to IL-3, GM-CSF
      and SCF was enhanced by co-incubation with IL-11, and this effect was reversed in
      blocking experiments by the anti-IL-11 Moab. When tested on primary AML samples,
      IL-11 alone showed little, if any, proliferative activity. However, it increased
      the IL-3-dependent blast colony formation in eight out of eight cases and GM-CSF
      in seven cases. IL-11 also augmented synergistically the number of CFU-L
      stimulated by SCF in seven cases. A combination of three factors (IL-11, SCF and
      IL-3) yielded optimal colony formation. The BRDU studies showed the significant
      increase of AML cells in S-phase when IL-11 was combined with SCF, whereas the
      two CSF had no activity on their own. Positive interaction was also observed when
      IL-11 was added to IL-3 supplemented cultures in five out of eight cases tested.
      Reverse transcriptase-polymerase chain reaction amplification (RT-PCR)
      demonstrated the constitutive expression of IL-11 mRNA in all the cell lines and
      11/12 AML samples studied at diagnosis. These results indicate that IL-11 is
      expressed in leukaemic myeloid cells and that their proliferation is regulated by
      the cytokine which acts as a synergistic factor.

PMID- 8547069
TI  - The role of haemopoietic growth factors in the pathogenesis of the early anaemia
      of premature infants.
AB  - The anaemia of prematurity has been attributed to an insufficient erythropoietin
      (Epo) level. However, haemopoiesis is known to be regulated by a cohort of growth
      factors including interleukin-3 (IL-3), IL-6, stem cell factor (SCF), granulocyte
      monocyte-colony stimulating factor (GM-CSF) and insulin-like growth factors-I and
      -II (IGF-1, IGF-II). Circulating levels of these growth factors were measured in
      cord blood at the following gestational ages: 25-28 weeks, 29-32 weeks, 33-36
      weeks and > 37 weeks. This study indicates that low concentrations of IGFs as
      well as a low Epo level in early gestational ages may play a role in anaemia of
      prematurity.

PMID- 8547070
TI  - Three unrelated Gaucher's disease patients with three novel point mutations in
      the glucocerebrosidase gene (P266R, D315H and A318D).
AB  - Three novel point mutations were detected in the glucocerebrosidase gene of three
      unrelated Gaucher's disease patients by direct sequencing of PCR products. The
      first is a C to G change at position 4263 in the genomic sequence (exon 7) which
      results in a proline to arginine change at position 266 in the mature enzyme
      (P266R). The second is a G to C change at position 5276 in the genomic sequence
      (exon 8) which results in an aspartic acid to histidine change at position 315
      (D315H). The third is a C to A change at position 5286 in the genomic sequence
      (exon 8) which results in an alanine to aspartic acid change at position 318
      (A318D). The first mutation destroys an AvaII restriction endonuclease site, the
      second creates a BspMI site and the third creates a BamH I site.

PMID- 8547071
TI  - Band 4.2 Shiga: 317 CGC-->TGC in compound heterozygotes with 142 GCT-->ACT
      results in band 4.2 deficiency and microspherocytosis.
AB  - A novel compound heterozygous mutation of 317 CGC-->TGC with 142 GCT-->ACT in
      human red cell band 4.2 deficiency is described. A proband and his son suffered
      from compensated haemolysis with nearly complete deficiency of red cell band 4.2.
      Their red cell morphology exhibited microspherocytosis resembling classic
      hereditary spherocytosis (HS). Sodium dodecylsulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) showed band 4.2 to be nearly missing (< 1% of normal
      controls) with the presence of 74 kD and 72 kD isoforms in trace amounts. Other
      family members (daughters older and younger than the son) exhibited nearly normal
      amounts of 72kD as a wild form of band 4.2 on SDS-PAGE with the presence of the
      74kD isoform in a trace amount. The proband and his son demonstrated two compound
      heterozygous mutations in trans: i.e. nucleotide (nt) 949 CGC-->TGC (codon 317
      Arg-->Cys) in exon 7 and nt 424 GCT--ACT (codon 142 Ala-->Thr) in exon 3 of the
      band 4.2 gene. The two daughters demonstrated only the mutation of nt 949 CGC-
      >TGC in exon 7 in heterozygous states, but no 142 mutation. Therefore the proband
      and his son were compound heterozygotes of these two mutations in trans. It is
      interesting to note that the 74 kD isoform of band 4.2 protein existed in a trace
      amount in the two daughters in spite of the absence of the 142 Ala-->Thr
      mutation. In addition, even in the presence of the 142 mutation in one allele in
      the proband and his son, their red cell morphology demonstrated classic HS with
      microspherocytosis, although a homozygous state of the 142 mutation known as the
      Nippon type of band 4.2 deficiency exhibits ovalostomatocytosis.

PMID- 8547072
TI  - Fludarabine-related autoimmune haemolytic anaemia in patients with chronic
      lymphocytic leukaemia.
AB  - We have treated 52 patients with chronic lymphocytic leukaemia (CLL) with
      fludarabine; 12 developed severe autoimmune haemolysis. Only three had a previous
      history of haemolytic anaemia. Six out of eight patients retreated with
      fludarabine after control of their haemolysis developed an exacerbation of the
      haemolytic anaemia. The cause of autoimmune phenomena in CLL is not known, but
      our findings reinforce the view that they are caused by a disturbance in
      immunoregulatory T cells. Fludarabine is a known suppressor of T-cell function.

PMID- 8547073
TI  - Polyclonal hypergammaglobulinaemia in a case of B-cell chronic lymphocytic
      leukaemia: the result of IL-2 production by the proliferating monoclonal B cells?
AB  - SEQ DATA who developed polyclonal hypergammaglobulinaemia: 38.3 milligrams
      polyclonal IgG, 0.97 milligram IgA and 0.33 milligram IgM. Immunophenotyping
      showed a monoclonal lymphocytic population CD19+ CD5+ CD40+ CD23+, low sIg+
      (95%), kappa type in the great majority (96%). RT-PCR of immunoglobulin genes
      gave evidence of monoclonal rearrangement of the IgM type. Our tests showed that
      IL-2 was produced when leukaemic B cells were stimulated with phorbol myristate
      acetate, ionomycin and lipopolysaccharide. In addition, transfections with the
      full IL-2 promoter or elements thereof revealed that IL-2 expression is inducible
      and mediated through the NF-kB-promoter element. Finally, the amount of IL-2
      secreted by these cells is about 39 ng/ml/10(6) cells, which is remarkably high
      for non-T cells. These results suggest that the large amounts of polyclonal IgG
      seen in this case of B-CLL are secreted by normal B cells which are in turn
      stimulated by IL-2 produced by proliferating monoclonal (leukaemic) B cells.
      Under cyclosporin A treatment, immunoglobulin secretion and B cell count remained
      low.

PMID- 8547074
TI  - Homozygous loss of the MTS1/p16 and MTS2/p15 genes in lymphoma and lymphoblastic
      leukaemia cell lines.
AB  - The genes MTS1/p16 and MTS2/p15 located in 9p21 encoding cyclin-dependent kinase
      4 inhibitors are homozygously deleted in a number of different tumour cell lines.
      By PCR analysis of 30 cell lines, including 10 acute lymphoblastic leukaemia
      (ALL) and 20 lymphoma cell lines, we found homozygous deletions of at least one
      locus in 11 (37%) cell lines. MTS1-specific sequences were deleted in 70% of ALL
      (reaching 86% in T-cell ALL) but in none of the non-Hodgkin's lymphoma (NHL) cell
      lines. MTS2-specific sequences were deleted in 40% of ALL and 17% of NHL cell
      lines. We observed a higher frequency of MTS1 deletions in ALL than in NHL (P <
      0.001) and in T-cell neoplasms compared to B-cell neoplasms (67% v 6%; P =
      0.001). In ALL-derived cell lines deletions of the MTS2 gene only occurred in
      cases with MTS1 deletions but in NHL only in cases without MTS1 deletions.

PMID- 8547075
TI  - Nasal natural killer (NK) cell lymphoma: report of a case with activated NK cells
      containing Epstein-Barr virus and expressing CD21 antigen, and comparative
      studies of their phenotype and cytotoxicity with normal NK cells.
AB  - Malignant lymphomas arising from the nasal cavity have been considered to be
      derived from T cells, but recent surface marker studies suggest that more than
      half of the lymphomas are derived from natural killer (NK) cells. Here we
      describe a case of nasal lymphoma whose lymphoma cells were identified as NK
      cells by morphological, phenotypic, immunogenotypic, and functional studies. We
      believe this is the first study with functional evidence of NK activity. When
      compared with normal freshly isolated NK cells or activated NK cells, the surface
      phenotypes and NK activity of the patient tumour cells were those of the
      activated, but not resting, NK cells. Also, Epstein-Barr virus (EBV) was detected
      in the tumour cells and the lymphoma cells were found to be monoclonally
      expanded. The patient's lymphoma cells also expressed EBV receptor CD21 (CR2) and
      CD30 (Ki-1) that have not been described on normal NK cells. We therefore
      examined highly enriched NK cells of normal donors, and found that some resting
      and/or activated NK cells express these antigens.

PMID- 8547076
TI  - The expression of mRNA for fibrinogen in megakaryocytes isolated from patients
      with T-cell lymphoma.
AB  - The expression of fibrinogen mRNA was studied by in situ hybridization in freshly
      isolated megakaryocytes in 14 newly-diagnosed patients: seven with non-Hodgkin's
      lymphoma (NHL), three with immune thrombocytopenic purpura (ITP) and four
      haematologically normal patients prior to coronary artery bypass surgery.
      Fibrinogen mRNA in megakaryocytes was not detected in ITP, B-cell lymphomas or in
      healthy donors. However, it was present in all patients with the high-grade T
      cell lymphomas, both with and without thrombocytopenia.

PMID- 8547077
TI  - Pharmacokinetic and pharmacodynamic studies of subcutaneously administered
      recombinant human interleukin-3 following chemotherapy for non-Hodgkin's
      lymphoma.
AB  - The pharmacokinetics and the pharmacodynamic profile of subcutaneously
      administered recombinant human non-glycosylated interleukin-3 (rhIL-3) was
      studied in lymphoma patients after standard CHOP chemotherapy. 30 patients
      received 0.5, 1.0, 5.0, 7.5 and 10 micrograms/kg (six patients at each dose
      level) of rhIL-3 for 14 d. Serum rhIL-3 samples were obtained regularly, during
      the treatment and serially over a 24 h period on the first (cycle day 2) and the
      last (cycle day 15) day of rhIL-3 treatment for pharmacokinetic evaluation.
      Following s.c. injection on cycle day 2. the maximum rhIL-3 serum concentration
      ranged from 289 pg/ml (0.5 micrograms/kg) to 4690 pg/ml (10 micrograms/kg). Both
      the maximum serum concentration (R = 0.90. P < 0.0001) and the area under the
      serum concentration-time curve (R = 0.95, P < 0.0001) were related to dose. The
      elimination half-life T1/2 beta was 160 min for 0.5 micrograms/kg and 134 min for
      10 micrograms/kg, with no apparent dose relationship. The systemic clearance of
      3.0-6.0 ml/min/kg was comparable at all dose levels. No significant difference
      was noted between pharmacokinetic parameters on the first day of rhIL-3 and the
      last day of treatment, and no accumulation of the drug was noted throughout the
      study. The pharmacokinetic parameters correlated poorly to the clinical response
      of the growth factor. where dose in micrograms/kg seemed to be the most important
      single factor.

PMID- 8547078
TI  - Comparative quantitative expression of bcl-2 by normal and leukaemic myeloid
      cells.
AB  - Expression of the bcl-2 oncoprotein by AML blasts has previously been
      demonstrated to be heterogenous with high levels of bcl-2 expression being
      associated with a low complete remission rate and poor survival. We have
      quantified bcl-2 expression in AML blasts in relation to expression of the CD34
      antigen and in comparison to CD34-positive cells from normal bone marrow. When
      expressed as molecules of equivalent soluble fluorochrome (MESF) per cell. AML
      blast cell bcl-2 expression varied from 11.1 to 99.9 x 10(3) (median 39.4 x
      10(3), n = 56) with 28.5% of patients expressing high MESF values (> 50 x 10(3))
      and 16% of patients expressing low MESF values (< 20 x 10(3), the remainder
      expressing intermediate values. There was no significant difference between
      intensity of bcl-2 expression and FAB classification in the de novo AML cases;
      and there was no significant differences between de novo and secondary AML cases.
      Blasts from CD34+ AML patients expressed significantly higher levels of bcl-2
      (mean MESF 43.6 x 10(3), n = 36) than CD34- AML patients (mean MESF 31.7 x 10(3),
      n = 19). In five cases of CD34+ AML, bcl-2 expression was determined on purified
      CD34+ and CD34- blast cell populations. In all cases CD34+ blasts were found to
      express significantly higher bcl-2 MESF values compared to the CD34- fraction.
      Purified CD34+ cells from normal bone marrow consistently expressed high levels
      of bcl-2 (MESF > 75 x 10(3), n = 4), which was comparable to that found on CD34+
      AML cells. Our results suggest that the poor prognosis previously associated with
      AML blasts expressing the CD34 antigen may in part be related to high expression
      of bcl-2. Also the ability to measure bcl-2 in AML blasts quantitatively by flow
      cytometry and to categorize patients into discrete groups may be of value as a
      prognostic indicator in AML.

PMID- 8547079
TI  - Busulfan and melphalan as conditioning regimen for autologous peripheral blood
      stem cell transplantation in multiple myeloma.
AB  - Twenty-four patients with multiple myeloma (MM), three (12.5%) in complete
      remission (CR) and 21 (87.5%) in partial remission (PR) were treated with high
      dose chemotherapy (HDCT) (busulfan 12 mg/kg+melphalan 140 mg/m2) as preparative
      regimen for autologous peripheral blood stem cell (PBSC) transplantation. These
      cells were previously collected by leukapheresis after mobilization by high-dose
      cyclophosphamide (HD Cy)+rhGM-CSF (18 patients) or rhG-CSF alone (six patients).
      Considering 23 evaluable patients following HDCT, the CR rate was 58% (14
      patients) and the PR rate was 38% (nine patients). One transplant-related death
      occurred following this regimen (4%). With a median follow-up of 20 months (range
      4-34) after transplantation, 21 patients are alive (87%). Disease progression
      after transplantation was observed in four patients. Overall and relapse-free
      actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%)
      remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis.
      Busulfan+melphalan is a safe and feasible conditioning regimen for APBSCT in MM
      with acceptable toxicity and a high objective response rate, which may result in
      prolonged survival.

PMID- 8547080
TI  - Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to
      growth factor deprivation, X-irradiation and glucocorticoids.
AB  - Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR
      ABL expression is a mechanism that might contribute to clonal expansion in
      chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing
      radiation and many chemotherapeutic agents can occur by the apoptotic pathway,
      inhibition of apoptosis would be expected to confer a relative resistance to
      these treatments. Similarly, cells deprived of growth factors in vitro die by
      apoptosis, and inhibition of apoptosis would therefore be expected to allow cells
      to survive better in growth factor-deprived conditions. We found that the
      survival of normal and CML myeloid progenitors was the same after in vitro
      incubation in deprived conditions and after treatment with X-irradiation or
      glucocorticoids. We also found that mature cells in colonies produced by CML
      progenitors (CFU-GM) did not survive better than those produced by normal
      progenitor cells. Flow cytometric analysis of propidium iodide-stained cells
      provided a direct indication that the degree of apoptosis may correspond to the
      degree of deprivation. These results suggest that inhibition of apoptosis may not
      be the primary mechanism whereby BCR-ABL influences the expansion of the
      malignant clone in CML.

PMID- 8547081
TI  - Serum concentrations of E-selectin, P-selectin, ICAM-1 and interleukin 6 in acute
      leukaemia patients with chemotherapy-induced leucopenia and bacterial infections.
AB  - Serum concentrations of E-selectin (CD62E), P-selectin (CD62P), ICAM-1 (CD54) and
      interleukin 6 were investigated in acute leukaemia patients with chemotherapy
      induced leucopenia and complicating bacterial infections. Serum concentrations of
      both E-selectin and P-selectin were decreased in the leucopenic patients without
      infections when compared with levels before chemotherapy; and serum
      concentrations of both E-selectin and P-selectin showed a further decrease during
      complicating bacterial infections. In contrast to the leukaemia patients,
      previously healthy individuals with meningococcal disease showed markedly
      elevated serum concentrations of E-selectin and normal levels of P-selectin
      during infection. Serum concentrations of ICAM-1 and interleukin 6 increased
      during bacterial infections in the acute leukaemia patients with chemotherapy
      induced leucopenia. The alterations in serum concentrations of soluble adhesion
      molecules and interleukin 6 reversed when clinical signs of bacterial infections
      resolved during antibiotic therapy. Our results demonstrate that acute leukaemia
      patients with chemotherapy-induced cytopenia show altered levels of both soluble
      adhesion molecules and interleukin 6 during complicating bacterial infections.

PMID- 8547082
TI  - Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes:
      response to immunosuppressive therapy.
AB  - We analysed the clinical features, course and response to immunosuppressive
      therapy in 30 patients with autoimmune disorders associated with myelodysplastic
      syndromes (MDS). 18 patients with MDS developed acute systemic autoimmune
      disorders. Common manifestations were skin vasculitis (n = 15) and arthritis (n =
      11). Seven patients had an acute clinical syndrome of vasculitic skin rash, fever
      and arthritis with peripheral oedema in three and pulmonary infiltrates in five
      of these seven patients. Other acute manifestations included pericarditis,
      pleural effusions, skin ulceration, seizures, myositis and peripheral neuropathy.
      Chronic or isolated autoimmune manifestations (n = 11) included
      glomerulonephritis, polyneuropathy, pyoderma gangrenosum, ulcerative colitis and
      polyarthritis. Classic connective tissue disorders recognized included relapsing
      polychondritis, polymyalgia rheumatica, Raynaud's syndrome and Sjogren's
      syndrome. Autoimmune manifestations responded to immunosuppressive therapy
      (primarily prednisone) in 26/27 patients treated. Furthermore, cytopenias
      improved substantially in six patients, including complete normalization of
      peripheral blood counts in two patients with cytogenetic remission in one.
      Patients with a haematological response to immunosuppressive therapy had improved
      survival compared with non-responding patients. The autoimmune syndrome was
      implicated as a primary cause of death in 8/17 patients who died. Autoimmune
      manifestations may be more common than previously recognized in patients with
      MDS. Aggressive therapy with immunosuppressive agents in selected patients often
      controls autoimmune phenomena associated with MDS and may lead to haematological
      responses in some patients.

PMID- 8547083
TI  - Diagnosis of transfusion-associated graft-versus-host disease by polymerase chain
      reaction in fludarabine-treated B-chronic lymphocytic leukaemia.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD), has rarely been
      reported associated with B-chronic lymphocytic leukaemia (B-CLL). We report a
      patient diagnosed with B-CLL, previously treated with fludarabine, who developed
      TA-GVHD after being transfused during surgery for splenectomy. Diagnosis was
      confirmed by polymerase chain reaction (PCR) detection of donor DNA in the
      patient, by amplification of Y-chromosome sequence and analysis of minisatellite
      polymorphisms. B-CLL patients treated with fludarabine appear to be at risk for
      TA-GVHD and should be regarded as candidates for transfusions with irradiated
      blood products. This case illustrates that PCR is a rapid technique for the early
      diagnosis of TA-GVHD.

PMID- 8547084
TI  - Long survival after splenic immunoblastic transformation of Waldenstrom's
      macroglobulinaemia.
AB  - Immunoblastic transformation of Waldenstrom's macroglobulinaemia is normally a
      preterminal event. We report a case in which the immunoblastic transformation
      appeared to be limited to the spleen. Splenectomy was more effective than
      cytotoxic chemotherapy in controlling the disease, and the patient remains free
      of disease 45 months later.

PMID- 8547085
TI  - Evidence for a polyclonal nature of the cell infiltrate in sinus histiocytosis
      with massive lymphadenopathy (Rosai-Dorfman disease).
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman
      disease, is rare histiocytic disorder of known origin which shares several cell
      markers with Langerhans' cell histiocytosis (LCH). Although Rosai-Dorfman cells
      exhibit an aberrant immunophenotype, the indolent clinical course of SHML
      suggests a reactive disorder rather than a neoplastic process. Until recently
      this was prevailing opinion concerning LCH also, but recent studies have detected
      clonal histiocytes in all forms of this latter condition, which is therefore
      considered a clonal neoplastic disorder with highly variable biological
      behaviour. To determine whether the histiocytic proliferation in SHML is
      polyclonal or clonal we used X-linked polymorphic loci to assess clonality in
      lesional tissues in two women. Polymorphic regions of the human androgen receptor
      (HUMARA) locus were amplified by polymerase chain reaction (PCR) analysis. The
      HUMARA locus was informative in both cases and, following digestion with
      methylation-sensitive enzymes, typical polyclonal X-inactivation patterns were
      observed. Since abnormal cells accounted for > 90% lesional tissue cells, we
      conclude that Rosai-Dorfman histiocytic proliferation was polyclonal in the women
      studied.

PMID- 8547086
TI  - Monoclonal proliferation of CD4+ large granular lymphocytes with cytolytic
      activity.
AB  - A rare case of monoclonal proliferation of CD3+4+8- T-cell receptor-alpha beta+
      large granular lymphocytes (LGL) is presented. CD4+ LGL in the present case
      showed spontaneous cytotoxicity against herpes simplex virus-infected cells and
      antibody- and lectin-dependent cytotoxicity. Perforin, which is one of the
      important cytolytic mediators of cytotoxic T cells (CTL) and natural killer
      cells, was abundantly expressed in CD4+ LGL of this case. The present case
      suggests that perforin-positive CD4+ CTL, which have recently been shown in the
      in vitro studies, certainly exist in vivo.

PMID- 8547087
TI  - Trisomy 3 is a consistent chromosome change in malignant lymphoproliferative
      disorders preceded by cold agglutinin disease.
AB  - Cold-antibody autoimmune haemolytic anaemia is a rare entity that has been
      associated with a wide variety of pathological processes, including malignant
      lymphoproliferative disorders. In this retrospective study we recorded, as far as
      possible, clinical, haematological, immunological, morphological, pathological,
      cytogenetic and molecular data on 10 patients with cold agglutinin disease (CAD).
      Cytogenetic anomalies were found in four cases in which an underlying lymphoma
      could be evidenced. Trisomy 3 was the only recurrent aberration in our series. It
      was observed in all patients with abnormal karyotype, either as a complete
      trisomy or as a partial trisomy of the long arm. The importance of this
      particular karyotypic aberration in the monitoring of CAD is emphasized.

PMID- 8547088
TI  - Thrombopoietin is not responsible for the thrombocytosis observed in patients
      with acute myeloid leukemias and the 3q21q26 syndrome.
AB  - Patients with acute myeloblastic leukaemia (AML) and chromosomic abnormalities of
      the 3q21;q26 region have striking dysmegakaryopoiesis and normal or increased
      platelet counts. Leukaemic cells ectopically express the Evi-1 gene which maps to
      human chromosome 3q26:q27. Thrombopoietin (TPO) has been cloned recently and
      shown to be the major hormone stimulating both megakaryocytopoiesis and
      thrombopoiesis. The TPO gene maps to human chromosome 3q26. For this report we
      studied four patients with typical 3q21:q26 syndrome. Karyotype analysis showed
      inv(3)(q21;q26) in three cases and t(3:3)(q21;q26) in one case. Although high
      levels of Evi-1 transcripts could be detected in mRNA isolated from the bone
      marrow cells of these patients by Northern blot analysis, no TPO transcripts were
      detectable by RT-PCR technique on the same mRNA samples. These results
      demonstrate that TPO gene transcription is not activated in patients with 3q26
      chromosomic abnormality, and that abnormal TPO production is not responsible for
      the observed thrombocytosis.

PMID- 8547089
TI  - Minor breakpoint cluster region (m-BCR) positive chronic myeloid leukaemia with
      an acute lymphoblastic leukaemia onset: a case report.
AB  - m-BCR chronic myeloid leukaemia (CML) is a rare entity. We report a patient
      presenting with Philadelphia (Ph)-positive, m-BCR-positive acute lymphoblastic
      leukaemia (ALL) who achieved complete remission after induction chemotherapy, but
      showed a majority of Ph-positive mitoses during this remission. A diagnosis of m
      BCR CML was established and the patient was given interferon alpha therapy. This
      is the first m-BCR CML presenting as ab initio ALL. This report emphasizes the
      importance of karyotyping Ph-positive ALL during remission so as not to
      misdiagnose CML patients who can benefit from Interferon therapy.

PMID- 8547090
TI  - CD34+ cell immunoselection from G-CSF-alone-primed peripheral blood in children
      with low body mass.
AB  - We report the data of CD34+ cell immunoselection from peripheral blood after G
      CSF-alone mobilization (10 micrograms/kg/d s.c.) in nine children with
      neuroblastoma (median age 4-5 years (2-8), median body weight 16 kg (10-20).
      Leukaphereses were carried out on a Cobe Spectra separator and two consecutive
      harvests (4 blood volumes processed) were used for immunoselection on a Ceprate
      column. The yield of CD34+ cells in the purified fraction was 50% (23-80), with a
      median number of 2.8 x 10(6) CD34+ cells/kg (1-9.4). All patients were reinfused
      with selected CD34+ cells after busulfan 600 mg/m2 +melphalan 180 mg/m2 and
      achieved successful haemopoietic recovery.

PMID- 8547091
TI  - Purinoceptors on blood platelets: further pharmacological and clinical evidence
      to suggest the presence of two ADP receptors.
AB  - Platelet aggregation by ADP plays a major role in the development and extension
      of arterial thrombosis. The antithrombotic thienopyridine compounds ticlopidine
      and clopidogrel have proved useful tools to investigate the mechanisms of ADP
      induced platelet activation. In essence, although clopidogrel has been shown to
      completely and selectively block ADP-induced platelet aggregation, G protein
      activation and inhibition of adenylyl cyclase, this drug does not affect shape
      change and Ca2+ influx. Binding studies, using the non-hydrolysable ligand
      [33P]2MeSADP, have shown that human platelets contain about 600 high-affinity
      binding sites for 2MeSADP (Kd approximately 5 nM). These sites present
      pharmacological characteristics of a P2T receptor. Clopidogrel treatment reduces
      the number of sites by 70% on rat platelets (from 1200 to 450) and leaves the
      residual binding sites resistant to clopidogrel. Moreover, patients with
      congenital impairment of ADP-induced platelet aggregation but normal shape change
      display very low levels of [33P]2MeSADP binding sites. The current data thus
      strongly suggest the presence of two ADP receptors, one responsible for shape
      change and rapid Ca2+ influx and the other a Gi protein-coupled receptor
      responsible for Ca2+ mobilization from internal stores, inhibition of adenylyl
      cyclase and platelet aggregation.

PMID- 8547092
TI  - Quantitation of reticulated platelets: methodology and clinical application.
AB  - A practical technique for the preparation and analysis of reticulated platelets
      is described. The use of fixed platelet-rich plasma has given optimal results and
      sample stability. This technique has detected consumptive causes of a platelet
      count < 80 x 10(9)/l with a positive predictive value of 96% and negative
      predictive value of 100%. The course of the reticulated platelet percentage (RP%)
      in patients with resolving thrombocytopenic states is described, contrasting the
      elevation seen in consumptive disorders with the fall in aplastic states. In
      patients undergoing stem cell transplant procedures a rise in the RP% precedes
      the rise in the platelet count, indicating that the reticulated platelets
      represent cells that are recently released from the bone marrow. The RP% peak in
      patients receiving autologous peripheral blood progenitor cell transplants is
      higher and more closely temporally related to the recovery of platelet count than
      it is in patients receiving autologous bone marrow transplants.

PMID- 8547093
TI  - Factor XIIIA Calgary: a candidate missense mutation (Leu667Pro) in the beta
      barrel 2 domain of the factor XIIIA subunit.
AB  - Molecular analysis performed on a Canadian family with congenital factor XIII
      deficiency revealed a homozygous missense mutation (Leu667Pro) in exon 14 of the
      A subunit gene in three affected siblings. The mutation results from a T-to-C
      transition at nucleotide position 2087 and generates a new Msp1 restriction site.
      Digestion of an amplified fragment containing exon 14 with this restriction
      enzyme enabled the heterozygous allele to be identified in both parents (who were
      third cousins) and three other family members. SSCP analysis detected no
      additional mutations in the coding or consensus splice sequences of the A subunit
      gene. The mutant nucleotide substitution was absent in 60 normal alleles and 10
      unrelated patients with XIIIA deficiency. Leu667 is located in the carboxyl
      terminal beta barrel 2 domain of the A subunit molecule. Computer modelling based
      on 3D crystallographic data predicts that the mutant protein has aberrant folding
      and is likely to be rapidly degraded following translation.

PMID- 8547094
TI  - Characterization of mutations within the factor VIII gene of 73 unrelated mild
      and moderate haemophiliacs.
AB  - To screen for mutations within the factor VIII gene of 101 patients (85
      unrelated), we used denaturing gradient gel electrophoresis (DGGE) after DNA
      amplification of target regions, including all coding regions except for the
      middle part (amino acid 757 to amino acid 1649) of the B domain. With this
      method, missense mutations were identified in 86% of unrelated patients. 41
      different mutations were identified: 25 of them have not been described
      previously. Five of the genotypes are associated with CRM+ and 26 with CRMred
      status. Patients who are definitely related to each other showed no differences
      in DNA sequence. One patient showed two different base pair alterations, the
      first at amino acid 469 [ala(GCA-->gly(GGA)] and the second at position 473
      [tyr(TAT)-->cys(TGT)]. One patient with an amino acid change at position 1689
      [arg(CGC)-->his(CAC)] has developed an inhibitor against factor VIII.

PMID- 8547095
TI  - Resistance to activated protein C in healthy women taking oral contraceptives.
AB  - Resistance to activated protein C (APC) is at present considered the most
      frequent laboratory abnormality in patients with deep-vein thrombosis. An
      increased risk for venous thrombosis is associated to the use of oral
      contraceptives (OC). We studied APC sensitivity in 50 healthy women taking OC and
      in 50 healthy controls, matched for age, smoking habit, educational and social
      levels, and the main biochemical routinary parameters. Subjects with a personal
      or familial history of thrombosis and also with chronic or acute diseases were
      excluded. Protein C, protein S, antithrombin III and lupus anticoagulant activity
      (LAC) were also evaluated. Increased fibrinogen and protein C levels, decreased
      protein S. and shortened PT and APTT were also observed in women taking OC. APC
      sensitivity ratio (APC-SR) was significantly lower in the OC group than in a
      control group (2.6 +/- 0.38 v 2.81 +/- 0.35, P < 0.01). Seven of eight women with
      APC ratio < or = 2 (APC resistant) were OC users: the difference of prevalence
      was statistically significant (chi-squared test, P < 0.05). Only two out of eight
      women were found heterozygous for the Leiden factor V mutation. Two APC-resistant
      women without the Leiden mutation subsequently discontinued OC and both then
      normalized their APC-SR. We conclude that acquired factors, i.e. oral
      contraceptives, may play an important role in determining plasma APC resistance.

PMID- 8547097
TI  - Inter-individual variation in half-life of infused recombinant factor VIII is
      related to pre-infusion von Willebrand factor antigen levels.
AB  - In an attempt to explain the substantial inter-individual variability in half
      life of infused factor VIII (FVIII) among haemophilia A patients, we studied the
      correlation of pre-infusion von Willebrand factor antigen (vWFAg) levels and the
      half-life of a recombinant-DNA-derived FVIII (r-VIII SQ. Pharmacia, Sweden).
      Intra-individual variation in half-life was small (range of variation 0-2.1 h) in
      12 severely affected haemophiliacs who received two doses of FVIII concentrate.
      In contrast, inter-individual variation in half-life was large (range of half
      lives 6-28.8 h). A strong correlation between half-life and pre-infusion vWFAg
      levels was present (r = 0.87, P = 0.0003). We conclude that the half-life of
      infused recombinant FVIII is related to pre-infusion vWFAg levels in severely
      affected haemophilia A patients.

PMID- 8547096
TI  - The use of an anti-beta 2-glycoprotein-I assay for discrimination between
      anticardiolipin antibodies associated with infection and increased risk of
      thrombosis.
AB  - Antiphospholipid antibodies (aPAs), occurring in association with infection, are
      not generally associated with an increased risk of thrombosis. Anticardiolipin
      antibodies (aCL) from patients with infection, unlike those from patients with
      SLE, do not have the beta 2GPI cofactor requirements. Antibodies to beta 2GPI
      (alpha beta 2GPI) are more closely associated with a previous history of
      thrombosis than aCL in patients with SLE. In the present study we have
      investigated the reactivity of the alpha beta 2GPI assay for aPAs associated with
      infection. Serum from 114 patients with infections including syphilis (n = 11),
      tuberculosis (n = 63) and Klebsiella (n = 42) were assayed for alpha beta 2GPI
      and aCL antibodies. The incidence of aCL in serum of patients with tuberculosis.
      Klebsiella infection and syphilis was 6.0%, 5.0% and 64.0%, respectively, but all
      patients were negative for alpha beta 2GPI. These results indicate that the alpha
      beta 2GPI assay is negative in patients with transiently positive aCL assays
      associated with infection.

PMID- 8547098
TI  - Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic
      purpura: a report on 10 cases.
AB  - We treated 10 patients who had chronic refractory idiopathic thrombocytopenic
      purpura (ITP) with high-dose dexamethasone (DXM, 40 mg/d for 4 sequential days
      every month). The interval from diagnosis ranged from 49 to 300 months, and
      patients had previously received a median of 5.5 treatments (including
      splenectomy in nine cases). Median platelet count was 14 x 10(9)l (range 6-26 x
      10(9)/l) at the onset of DXM and eight patients had bleeding symptoms. Eight
      patients received at least three cycles of DXM. Five patients had a response
      (i.e. platelet count at least doubled and increased by > 20 x 10(9)/l), including
      one almost complete remission and four minor responses (MR). Of the MR, one was
      probably due to concurrent IVIg administration, and all four MR were transient,
      in spite of further cycles of DXM. In three patients DXM was a failure after
      three or four cycles. In two patients DXM had to be stopped after one course
      because of major side-effects (systemic hypertension with stroke and insulin
      dependent diabetes, respectively). In our experience, high-dose DXM had a
      relatively limited effect in chronic refractory ITP and was associated with
      severe side-effects in some cases.

PMID- 8547099
TI  - Hepatitis C virus infection in multi-transfused children with haematological
      malignancy.
AB  - Transmission of hepatitis C virus (HCV) is an important hazard of blood
      transfusion and may result in chronic liver disease. 98 children from Nottingham
      and Sheffield with haematological malignancies were studied to determine the
      prevalence of HCV infection by enzyme immunoassay and RT/PCR techniques. The
      children had been exposed to up to 184 donors through red cell and platelet
      transfusion, the majority prior to routine testing for HCV infection in blood
      donors. Only one sample showed evidence of HCV infection being both ELISA and
      RT/PCR positive. None of the samples taken since donor screening were positive.
      This provides reassurance as to the low rate of HCV acquisition in multi
      transfused patients in this part of the U.K. compared to other parts of the
      world.

PMID- 8547100
TI  - Duodenal expression of NF-E2 in mouse models of altered iron metabolism.
AB  - This study investigated the relationship between duodenal mucosal mRNA levels of
      the transcription factor, NF-E2, H-ferritin (a putative NF-E2 regulated gene) and
      iron absorption in mice. CD1-strain mice with normal and altered iron metabolism
      (hypoxic, iron-deficient, iron-loaded) and animals with genetic defects of iron
      metabolism (hypotransferrinaemia, beta-thalassaemia) were studied. Tissue RNA
      from these mouse models was subjected to reverse transcription and PCR
      amplification for NF-E2 and a stable ribosomal protein (S14) and the products
      analysed with an automated laser fluorescent sequencer. Duodenal NF-E2 mRNA
      levels were generally low and decreased in the hypoxic and iron-deficient groups,
      both of which exhibited elevated iron absorption as compared to controls. A
      modest increase in the NF-E2 mRNA level was seen in the iron-loaded mice, whose
      iron absorption was decreased. In contrast, both the genetic strains showed
      elevated NF-E2 mRNA levels in conjunction with raised iron absorption values.
      Only the iron-deficient group exhibited an alteration in the duodenal mucosal H/L
      ferritin ratio. Hence, no relationship was evident between the NF-E2 mRNA levels
      and the H/L ferritin ratio. These data indicate that NF-E2 is not the primary
      regulator of intestinal iron absorption.

PMID- 8547101
TI  - Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer
      Cytogenetic Group study.
AB  - Cytogenetic and clinical details are presented for 66 patients with myeloid
      malignancy and chromosome abnormalities of 3q21 and/or 3q26 (3qabns). Bone marrow
      and/or peripheral blood morphology was assessed for 52 cases. 3qabns in
      Philadelphia negative (Ph-ve) and positive (Ph+ve) cases were inv(3)(q21q26), (21
      Ph-ve, 6 Ph+ve); t(3;3)(q21;q26) (nine Ph-ve, four Ph+ve); and t(3;21)(q26;q22)
      (four Ph-ve, six Ph+ve). Ph-ve cases also had t(1;3)(p36;q21) (three cases), and
      t(3;5)(q21;q31)/(q21;q35)/(q26;q21) (five cases aged < 40 years). Three cases,
      aged < 30 years, had t(3;12)(q26;p13) which defines a new 3qabn subgroup.
      Monosomy 7 and/or 5q- accompanied inv(3) or t(3;3) in 17/30 cases. All cases had
      a myeloid malignancy (predominantly AML M1, M4 or M7), frequent trilineage
      myelodysplasia, and markedly abnormal megakaryopoiesis with micromegakaryocytes
      (< 30 microns). Thrombocytosis occurred in two cases only. Most Ph+ve cases were
      in myeloid blast crisis and in Ph+ve cases alone, micro-megakaryocytes were
      uniquely small (10 microns) in 7/11 cases. There were equal numbers of males and
      females. Seven secondary leukaemias were found in Ph-ve cases with inv(3),
      t(3;3), t(3;21), t(1;3) or del(3)(q21). Three cases with t(3;21) (one Ph+ve) were
      de novo AML or had de novo aplastic anaemia. Survival was rarely greater than 12
      months from detection of the 3qabn.

PMID- 8547102
TI  - Beta spectrin PRAGUE: a truncated beta spectrin producing spectrin deficiency,
      defective spectrin heterodimer self-association and a phenotype of spherocytic
      elliptocytosis.
AB  - Spherocytic elliptocytosis is a phenotypic hybrid between hereditary
      spherocytosis (HS) and hereditary elliptocytosis (HE) characterized by the
      presence of spheroovalocytes and spherocytes which exhibit increased osmotic
      fragility, indicating a deficiency of surface area. Both the spherocytic red cell
      morphology and the increased osmotic fragility distinguish this clinical entity
      from common HE. In contrast to common HE, the molecular basis of spherocytic
      elliptocytosis is unknown. Here we describe two members of a family who both have
      the characteristic features of spherocytic HE. We show that the underlying defect
      involves a G to C transversion at the -1 position of the acceptor splice site
      upstream of exon X of beta spectrin leading to skipping of exon X from the mutant
      beta spectrin mRNA allele. The mutant mRNA is present in reticulocytes in similar
      amounts as the normal mRNA. Pulse-labelling of erythroblasts prepared from
      peripheral blood in a two-phase liquid-culture system reveals a decreased
      synthesis of the truncated beta spectrin, a finding which is likely to underlie
      the moderately severe spectrin deficiency in the two patients. In addition, this
      mutant spectrin, similar to the previously reported spectrins, is defective in
      spectrin heterodimer self-association. The spectrin deficiency, which represents
      a common finding in the majority of patients with HS, together with weakened
      spectrin heterodimer self-association, as found in the majority of patients with
      common HE, provides a molecular explanation for the phenotype of spherocytic
      elliptocytosis in this kindred and, most likely, in other patients carrying
      similar beta spectrin mutations.

PMID- 8547103
TI  - Haemoglobinuria and haptoglobin in G6PD deficiency.

PMID- 8547104
TI  - On the discrepant post-DDAVP increase of FVIII:C and von Willebrand factor in
      some patients with severe von Willebrand's disease.

PMID- 8547105
TI  - Recombinant human granulocyte colony-stimulating factor and neutrophil phenotype.

PMID- 8547106
TI  - t(8;21) myelodysplasia: a further six cases.

PMID- 8547107
TI  - Virus infection-associated improvement of platelet counts in chronic ITP.

PMID- 8547108
TI  - Virus infection-associated improvement of platelet counts in chronic ITP.

PMID- 8547109
TI  - Hairy cell leukaemia, second cancer and occupational risk.

PMID- 8547110
TI  - In vitro red-cell proteolysis in hereditary spherocytosis: response to
      splenectomy.

PMID- 8547111
TI  - A prospective study to determine the frequency and clinical significance of
      alloimmunization post-transfusion.
AB  - There is debate in the literature about the frequency and importance of delayed
      transfusion reactions. This uncertainty could reflect the endpoints used
      (clinical or serological) and the type of study (typically retrospective or case
      series). In this report we describe a prospective investigation to determine the
      frequency of alloimmunization post transfusion and whether the alloantibody
      production is a laboratory event or has clinical relevance. A total of 2490
      patients were transfused 11,218 red cell concentrates. One or more blood samples
      were collected within 7 d post transfusion and screened for serological evidence
      of alloimmunization. If any antibody was detected the patient's post-transfusion
      sample was screened for biochemical evidence of haemolysis and the patient's
      chart reviewed for documentation of clinical signs of a transfusion reaction.
      Post transfusion alloimmunization occurred in 2.6% of the patients (95% CI 2.1
      3.6%), who had no detectable alloantibody in pre-transfusion testing. For those
      86 patients (3.5%) with alloantibodies detectable pretransfusion, 8.9% (95% CI
      3.6-17.4%) developed additional aloantibodies. The most common alloantibodies
      detected were anti-Jka, anti-E and anti-K. Despite the high frequency of
      serological evidence of delayed transfusion reactions, only one patient (0.05%)
      had clinical evidence of a delayed haemolytic transfusion reaction (95% CI 0.0
      0.27%). Serological evidence of a delayed transfusion reaction is common;
      however, these reactions rarely cause clinical symptoms.

PMID- 8547112
TI  - Haemopoietic progenitor cell differentiation: flow cytometric assessment in bone
      marrow and thymus.
AB  - We have recently shown that expression of any of the lineage-associated molecules
      CD2, CD7, CD10, CD19 or CD33 does not ensure lineage-commitment of CD34+
      progenitor cells. Further, normal progenitor cells and leukaemic blast cells have
      been shown to coexpress molecules associated with more than one haemopoietic
      lineage. Five-dimensional flow cytometric analysis of normal bone marrow cells
      was exploited to investigate the hypothesis of a developmental stage in
      haemopoiesis comprising CD34+ cells coexpressing CD2, CD5, CD7, CD10, CD19 and
      CD33 or any combination of these molecules. We report on a subpopulation of CD34+
      bone marrow cells constituting < 5% of the CD34+ cells and characterized by
      extensive coexpression of several molecules associated with the B lymphoid, T
      lymphoid and myeloid lineages. There is every probability that some cells display
      the CD34+ CD2+ CD5+ CD7+ CD10+ CD19+ CD33+ phenotype. Studies on postnatal
      thymocytes suggest that this may be the phenotype or one of a few phenotypes of a
      candidate thymus-seeding progenitor cell population. Finally, our findings that
      CD34+ as well as CD34+ CD5+ thymocytes can be driven into non-T-lymphoid
      differentiation by cytokines, support the notion that the thymus is seeded by
      uncommitted progenitors.

PMID- 8547113
TI  - Incidence of human parvovirus B19 DNA detection in blood donors.
AB  - 1000 serum samples from blood donors were tested for human parvovirus B19 (B19)
      DNA by a nested PCR assay: six samples were positive for B19 DNA. The frequency
      was 1/167 (0.6%), considerably higher than previous surveys (0.004-0.03%). Five
      of the six samples were also positive for anti-B19 IgM, indicating an acute phase
      of infection. It is recommended to screen for B19 DNA in blood products to
      prevent transfusion mediated viral infection for those susceptible such as
      immunocompromised patients and pregnant women.

PMID- 8547114
TI  - Detection of minimal residual disease in childhood acute lymphoblastic leukaemia
      using fluorescence in-situ hybridization.
AB  - Using centromere-specific probes and a fluorescence in-situ hybridization (FISH)
      technique in cases of childhood hyperdiploid acute lymphoblastic leukaemia (ALL),
      cells with extra copies of chromosomes can be differentiated from normal cells by
      their extra signals in both metaphase and interphase nuclei. In this way the
      entire cell population, not only those cells in division, can be analysed,
      thereby providing a valuable technique not only for determining leukaemia cell
      karyotype at diagnosis but also for the detection of minimal residual disease
      (MRD). We have conducted 161 analyses of remission bone marrow aspirates (BMs) in
      13 children with hyperdiploid ALL. Slides were analysed blind and in parallel to
      35 control samples. Control BMs showed very low numbers of trisomic cells (mean
      +/- 2 x SD = 0.13 +/- 0.34%). MRD was detected in 5/13 cases of ALL investigated
      while on chemotherapy. One out of five newly diagnosed cases and all three
      relapse cases of ALL had significantly raised levels of hyperdiploid cells in day
      28 BMs. The presence of detectable disease in day 28 BMs suggests the need for
      larger studies to find whether this data is of prognostic value.

PMID- 8547115
TI  - Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia.
AB  - The PRAD-1/CCND1 gene encodes Cyclin D1, a cyclin involved in cell cycle
      regulation at the G1-S transition. Over-expression of this gene is a highly
      specific molecular marker of mantle cell lymphomas (MCLs), but it may also be up
      regulated in some chronic lymphoproliferative disorders, mainly chronic
      lymphocytic leukaemia. We have examined PRAD-1/CCND1 gene expression by Northern
      blot and Western blot analysis in a series of 18 hairy cell leukaemias (HCLs),
      nine other splenic malignant lymphoproliferative disorders, and three
      normal/reactive spleens. Over-expression of the mRNA PRAD-1/CCND1 gene was
      observed in 16/18 HCLs, including one case of hairy cell leukaemia variant,
      whereas this molecular alteration was not found in other cases examined. mRNA
      levels varied from case to case, but they were lower than those observed in MCLs.
      At the protein level, Western blotting analysis showed Cyclin D1 protein
      expression in the 11 HCLs analysed. No bcl-1 rearrangements were seen with the
      MTC, p94PS and PRAD-1 (lambda-P1-4) probes used, and no PRAD-1/CCND1 gene
      amplification was detected in any case. These findings indicate that PRAD-1/CCND1
      is over-expressed at mRNA and protein levels in a high number of HCLs. However,
      the levels of expression are much lower than in MCLs, and this expression is not
      associated with bcl-1 rearrangements or PRAD-1/CCND1 gene amplification.

PMID- 8547116
TI  - Severe hypophosphataemia in autograft recipients during accelerated leucocyte
      recovery.

PMID- 8547117
TI  - Haemophagocytic syndrome due to babesiosis in a splenectomized patient.

PMID- 8547118
TI  - Circulating factors of the haemostatic systems as indicators of increased or
      reduced coronary risk.

PMID- 8547119
TI  - Expression of granulocyte colony-stimulating factor receptor increases with
      differentiation in myeloid cells by a newly-devised quantitative flow-cytometric
      assay.
AB  - In order to develop a non-isotopic quantitative assay of granulocyte colony
      stimulating factor (G-CSF) receptors on human or murine cells, we devised a flow
      cytometric assay using cells stained with biotin-labelled G-CSF (b-G-CSF) and a
      streptavidin-RED670 conjugate. For quantification, we applied the Kolmogorov
      Smirnov test and calculated the D value. The D value was evaluated from the
      degree of shift in two fluorescence profiles according to the increase of
      fluorescence intensity due to the specific binding of b-G-CSF to G-CSF receptors.
      A good correlation was observed between the number of G-CSF receptors obtained by
      the radioisotopic binding assay and the number calculated from the D value by the
      flow-cytometric assay. Then, expression of G-CSF receptors on human bone marrow
      cells, peripheral blood granulocytes and blast cells from patients with acute
      myeloid leukaemia (AML) were studied. G-CSF receptors was expressed on CD34+CD33
      , CD34+CD33+ and CD34-CD33+ cells in the following order: CD34-CD33+ > CD34+CD33+
      > CD34+CD33- cells, indicating that the receptors increased with maturation. The
      receptor levels of CD34-CD33+ cells in bone marrow were apparently lower than
      those of CD34-CD33+ cells in peripheral blood granulocytes. On the other hand, an
      abnormal expression pattern of G-CSF receptors was noted in AML blast cells.

PMID- 8547120
TI  - A novel factor-dependent human myelodysplastic cell line, MDS92, contains
      haemopoietic cells of several lineages.
AB  - A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic
      cell line, MDS92, was shown to contain several myeloid-lineage cells such as
      neutrophils, macrophages, eosinophils, and a small number of megakaryocyte
      lineage cells. Therefore this cell line possesses at least bipotential
      characteristics of myeloid- and megakaryocyte-lineages. Granulocyte colony
      stimulating factor clearly promoted the neutrophil alkaline phosphatase activity
      of MDS92 cells. To the contrary, the incidence and growth of CD41-positive cells
      were hardly affected by the addition of IL-6, IL-11, c-mpl ligand
      (thrombopoietin, TPO) or erythropoietin. TPO slightly supported the growth of
      CD34-positive cell fraction, but not CD41-positive cell fraction of MDS92 cells
      in combination with IL-3 or Steel factor. This cell line will be a useful tool
      for the study of MDS stem cells, but the mechanism of commitment of
      differentiation in MDS stem cells remains unknown.

PMID- 8547121
TI  - Adhesion molecule expression on CD34+ progenitor cells from normal and aplastic
      anaemia bone marrow.
AB  - Aplastic anaemia (AA) is a disease of bone marrow failure. Evidence has been
      produced for both a stem cell and a stromal cell defect in this disease. The
      contribution of deficient or defective cell adhesion molecules (CAMs) has not
      been determined. CAMs have been shown to be important in stem cell-stromal cell
      interactions and maintenance of haemopoiesis. In this study the expression of
      CAMs (LFA-1, LFA-3, ICAM-1. VLA-4, CD44, sLex and L-selectin) on CD34+ progenitor
      cells from 10 normal donors and eight patients with AA was investigated using
      double immunofluorescence. There was no significant difference in the percentage
      of CD34+ cells that were CAM+ between normal and AA bone marrow, suggesting that
      abnormal CAM expression on AA progenitor cells is not responsible for nor
      contributes to the pathogenesis of the disease. However, these findings do not
      exclude abnormal CAM function on progenitor cells, or abnormal expression or
      function of CAM ligands or counter-receptors on AA stromal cells.

PMID- 8547122
TI  - Band 3 Chur: a variant associated with band 3-deficient hereditary spherocytosis
      and substitution in a highly conserved position of transmembrane segment 11.
AB  - We studied a large Swiss family with dominantly inherited hereditary
      spherocytosis and band 3 (anion exchanger 1, AE1) deficiency. Band 3 cDNA was
      analysed by single-strand conformation polymorphism analysis and nucleotide
      sequencing. A new point mutation was found: G771D (GGC-->GAC). This change was
      present in all eight investigated patients but absent in four healthy members of
      the family. It is located at a highly conserved position in the middle of
      transmembrane segment 11, introducing a negative charge in a stretch of 16 apolar
      or neutral residues. None of the six amino-acid substitutions already known in
      this region as being associated with band 3 deficiency were recorded. To rule out
      any major transcriptional or post-transcriptional defect, we evaluated the amount
      of band 3 mRNA by RNase mapping using a band 3-protein 4.1 chimaeric probe.
      Similar mRNA amounts were present in patients and controls. Our results
      strengthen the view that some amino-acids, that are well conserved throughout the
      AE family, may be crucial for the insertion and/or the stabilization of band 3
      within the lipid bilayer. At the present time, most of the mutations altering
      such residues are located in the C-terminal region of band 3.

PMID- 8547123
TI  - Thalassaemic erythrocytes: cellular suicide arising from iron and glutathione
      dependent oxidation reactions?
AB  - Both beta-thalassaemic red blood cells and normal red blood cells (RBC)
      artificially loaded with unpaired alpha-haemoglobin chains exhibit increased
      amounts of membrane-bound haem and iron. In the model beta-thalassaemic RBC the
      amount of free haem and iron was as much as 20 times that which could have been
      contributed by the entrapped alpha-haemoglobin chains alone. This excess
      haem/iron arises from destabilization of haemoglobin via reactions between ferric
      iron (Fe3+), initially contributed by the unpaired alpha chains, and cytoplasmic
      constituents, primarily reduced glutathione (GSH). Indeed, in the presence of
      Fe3+ (100 microM) addition of even small amounts of GSH (0.5 mM) to dilute RBC
      haemolysates (0.15 mg haemoglobin/dl) greatly accelerated methaemoglobin
      formation. In contrast, lysates from GSH-depleted RBC demonstrated a
      significantly reduced rate of iron-mediated haemoglobin oxidation which was
      reversible by addition of GSH. The initiation, and subsequent propagation, of
      Fe(3+)-mediated haemoglobin oxidation was significantly inhibited by iron
      chelators. Finally, Fe(3+)-driven haemoglobin oxidation was synergized by low
      amounts of H2O2, an oxidant spontaneously generated in thalassaemic RBC. To
      summarize, the release of small amounts of free iron from unpaired alpha
      haemoglobin chains in the beta-thalassaemic RBC can initiate self-amplifying
      redox reactions which simultaneously deplete cellular reducing potential (e.g.
      GSH), oxidize additional haemoglobin, and accelerate the red cell destruction.

PMID- 8547124
TI  - Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia.
AB  - We prospectively studied 45 anaemic patients (37 women, 8 men) with chronic
      inflammatory rheumatic diseases. The combination of serum ferritin and CRP (as
      well as ESR) in its predictive capacity for bone marrow iron stores was examined.
      The relationship between other iron-related measurements (transferrin,
      transferrin saturation, soluble transferrin receptor, erythrocyte porphyrins and
      percentage of hypochromic/microcytic erythrocytes) and bone marrow iron stores
      was also investigated. Stainable bone marrow iron was taken as the most suitable
      standard to separate iron-deficient from iron-replete patients. 14 patients (31%)
      were lacking bone marrow iron. Regression analysis showed a good correlation
      between ferritin and bone marrow iron (adjusted R2 = 0.721, P < 0.0001). The
      combination of ferritin and CRP (ESR) did not improve the predictive power for
      bone marrow iron (adjusted R2 = 0.715) in this cohort of patients with low
      systemic inflammatory activity. With respect to the bone marrow iron content the
      best predictive cut-off value of ferritin was 30 micrograms/l (86% sensitivity,
      90% specificity). The other iron-related parameters both individually and when
      combined were less powerful in predicting bone marrow iron than ferritin alone.
      Only zinc bound erythrocyte protoporphyrin in combination with ferritin slightly
      improved prediction (adjusted R2 = 0.731). A cut-off point of 11% hypochromic
      erythrocytes reached a high specificity (90%), but was less sensitive (77%).

PMID- 8547125
TI  - Liver iron stores in patients with secondary haemosiderosis under iron chelation
      therapy with deferoxamine or deferiprone.
AB  - Total body iron stores including liver and spleen iron were assessed by non
      invasive SQUID biomagnetometry. The liver iron concentration was measured in
      groups of patients with beta-thalassaemia major or other posttransfusional
      siderosis under treatment with the oral iron chelator deferiprone (n = 19) and/or
      with parenteral deferoxamine (n = 33). An interquartile range for liver iron
      concentrations of 1680-4470 micrograms/g liver was found in these patients. In
      both groups a poor correlation between liver iron and serum ferritin values was
      observed. Repeated measurements of liver and spleen iron concentrations as well
      as determination of liver and spleen volume by sonography were performed in six
      patients under continuous deferiprone treatment for 3-15 months. In this group
      detailed information was obtained on the whole body iron store (5-36g) and the
      iron excretion rates (14-34 mg/d) for each patient. As indicated by decreasing
      liver iron concentrations, five out of six subjects showed a negative iron
      balance (2-13 mg/d). Conventional measurements of both serum ferritin and urine
      iron excretion gave fluctuating results, thus being only of limited use in the
      control of iron depletion therapy. The non-invasive biomagnetic liver iron
      quantification is a precise and clinically verified technique which offers more
      direct information on the long-term efficacy of an iron depletion therapy than
      the hitherto used methods. This technique may be of use in the clinical
      evaluation of new oral iron chelators.

PMID- 8547126
TI  - The metabolites of nitric oxide in sickle-cell disease.
AB  - Plasma NOx concentrations were raised in 22 acute painful crises in SCD. We have
      measured blood concentrations of nitric oxide metabolites (NOx) in sickle-cell
      disease (SCD), and shown that they are increased compared with healthy controls
      (P = 0.002), and haemoglobin E/beta-thalassaemic controls (P = 0.05).
      Concentrations in steady-state SCD were also higher than in healthy controls (P =
      0.04) but not significantly different from the concentrations at the beginning of
      painful crises (P = 0.34). Importantly, in 12 regularly exchanged sicklers, the
      mean pre-transfusion NOx concentration did not differ significantly from the
      control population (P = 0.52), suggesting that the changes in NO metabolism can
      be reversed. It is unlikely that the increased concentrations of NOx in SCD
      result from anaemia or haemolysis as the untransfused haemoglobin E/beta
      thalassaemics did not show increased levels.

PMID- 8547127
TI  - Clinical significance of serum cytokine patterns during start of fever in
      patients with neutropenia.
AB  - Serum concentrations of tumour necrosis factor alpha (TNF-alpha), interleukin-1
      receptor antagonist (IL-1ra), interferon gamma (IFN-gamma), interleukin-6 (IL-6)
      and interleukin-10 (IL-10) were studied in 31 patients with haematological
      malignancies during febrile neutropenia. Samples were obtained when blood
      cultures were performed (time 0) and, when possible, after 2, 4, 6, 12 and 24 h.
      Increased levels of all cytokines were detected after start of fever with peak
      values in gram-negative (Gr-) bacteraemias after 2 h (TNF-alpha, IL-1ra and IFN
      gamma), 4 h (IL-6) and 6 h (IL-10), respectively. At time 0 the median TNF-alpha
      value was higher in the Gr- group (80 pg/ml; range 54-516 pg/ml) as compared to
      both gram-positive bacteraemias (Gr+, 14 pg/ml; range 7-60 pg/ml; P < 0.05) and
      blood culture negative episodes (BCN, 8 pg/ml; range 0-87 pg/ml; P < 0.05).
      Furthermore, the peak values of TNF-alpha, IL-1ra, IL-6 and IL-10 during the 24 h
      study period were significantly and/or numerically higher in the Gr- group in
      comparison to the Gr+ and BCN groups, respectively. It may be concluded that
      neutropenic patients have increased levels of both pro- and anti-inflammatory
      cytokines at start of fever, with the highest values recorded during the first
      hours in Gr- bacteraemias. Prospective studies will show whether monitoring of
      serum cytokines may be used as an early diagnostic tool before results of blood
      cultures are available, which may have important therapeutic implications.

PMID- 8547128
TI  - Platelets prime PMN via released PF4: mechanism of priming and synergy with GM
      CSF.
AB  - Platelet-PMN interactions have been extensively studied and a spectrum of
      possible effects has been demonstrated. However, the physiological relevance of
      many of the observed in vitro phenomena remains obscure. Here we report a novel,
      and potentially pathophysiologically important, mechanism by which platelets can
      enhance PMN reactivity. We first observed that addition of platelets to PMN
      suspensions enhanced the chemiluminescence response of PMN to FMLP. This
      enhancement occurred without augmentation of superoxide generation and did not
      involve mutual platelet-PMN adhesion. The soluble material responsible was
      biochemically and immunologically identified as PF4 derived from platelet alpha
      granules. The alpha-granule release was shown to be selective and required
      minimal platelet stimulation. Since the PF4 effect did not influence NADPH
      oxidase activation, it differed markedly from that of other priming agents such
      as GM-CSF. Further studies showed that the PF4 effect was attributable entirely
      to the surface translocation and secretion of primary granule myeloperoxidase.
      There was marked synergy between PF4 and GM-CSF and both were required for
      maximal potentiation of PMN reactivity. These results demonstrate that PF4 and GM
      CSF employ different pathways in PMN priming. The ease with which platelets could
      release PF4 at sites of vessel-wall damage and inflammation suggests that
      platelet-PMN interaction via PF4 is likely to be of major pathophysiological
      importance.

PMID- 8547129
TI  - Patients with multiple myeloma requiring long-term dialysis: presenting features,
      response to therapy, and outcome in a series of 20 cases.
AB  - From January 1982 to December 1993, 30 patients with multiple myeloma (MM)
      required haemodialysis (HD) at our institution. The subgroup of 20 patients who
      survived more than 2 months on HD is the subject of this study. Four patients
      were already on HD, due to previous nephropathy, when MM was diagnosed. 13
      patients presented with acute renal failure and were on dialysis from the time of
      diagnosis. The remaining three cases developed renal failure later in the course
      of the disease. The objective response rate was 40% (8/20). Only two patients
      could discontinue HD (one had a late partial recovery and one received a kidney
      graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who
      survived < 1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup
      with a survival > 1 year mean hospitalization days was 9.6 (P < 0.001). The
      median survival was 20 months and six patients survived for > 3 years. In
      summary, patients with MM and severe renal failure who survive the first 2 months
      on dialysis have an objective response rate to chemotherapy of 40% and a median
      survival of almost 2 years, with 30% long-term survivors.

PMID- 8547130
TI  - High proportions of VLA-5- immature myeloma cells correlated well with poor
      response to treatment in multiple myeloma.
AB  - Using two-colour phenotypic analysis with anti-CD38 antibody, human myeloma cells
      can be classified into VLA-5- immature and VLA-5+ mature cells. We examined the
      relationship between variations of these subpopulations and clinical responses
      during treatment in multiple myeloma (MM). 39 patients with MM were treated with
      combined chemotherapy. First estimation of clinical responses after induction
      therapy showed that early clinical responses were correlated with the percentage
      of immature myeloma cells present after induction therapy (P < 0.01), not at
      diagnosis. After three courses of cyclic maintenance therapy, immature myeloma
      cells significantly decreased in proportion along with a decrease in total
      myeloma cells in maintained or more responsive cases (P < 0.01). On the other
      hand, immature myeloma cells were still found in high proportions in
      nonresponsive cases with no change (NC) or minor response (MR) (P < 0.01).
      Furthermore, in relapsing cases from partial response (PR) or progressive disease
      (PD) from nonresponsive cases, immature myeloma cells increased markedly.
      Therefore these results show that high proportions of VLA-5- immature myeloma
      cells remaining after induction therapy and during maintenance therapy correlate
      well with a declining clinical course of MM during maintenance therapy.

PMID- 8547131
TI  - CDKN2 gene deletion is not found in chronic lymphoid leukaemias of B- and T-cell
      origin but is frequent in acute lymphoblastic leukaemia.
AB  - Homozygous deletions of the cyclin-dependent kinase 4 (CDK4) inhibitor gene CDKN2
      (p16, MTS1) have been demonstrated to occur frequently in human cancer cell lines
      of different origin. However, in most primary tumours the frequencies of CDKN2
      deletions are not well defined. We studied primary samples of 100 patients with
      lymphoid leukaemias [B-lineage acute lymphoblastic leukaemia (ALL), n = 23; T
      ALL, n = 7; B-cell chronic lymphocytic (B-CLL) or prolymphocytic (B-PLL)
      leukaemia, n = 50; T-CLL/T-PLL, n = 20] using fluorescence in situ hybridization
      (FISH) with eight overlapping cosmid clones covering the region on chromosome
      band 9p21 containing CDKN2. We did not observe any CDKN2 deletions in the 70
      patients with chronic lymphoid leukaemias of B- or T-cell origin. Of the 23
      patients with B-lineage ALL, one (4%) exhibited a CDKN2 deletion: in this
      patient, two clones were detected, one exhibiting a hemizygous and the other a
      homozygous deletion. On chromosome banding analysis, four patients with B-lineage
      ALL had a 9p aberration, whereas all CDKN2 copies were retained. In contrast, six
      of the seven (86%) patients with T-ALL exhibited CDKN2 deletions (homozygous, n =
      4; hemizygous, n = 2). We conclude that hemizygous or homozygous deletions of the
      CDKN2 gene occur at high frequency in T-ALL and at low frequency in B-lineage
      ALL, supporting the role of this gene as a tumour suppressor, especially in T
      ALL. However, from our data there is no evidence that CDKN2 is involved in the
      pathogenesis of chronic lymphoid leukaemias of B- or T-cell origin.

PMID- 8547132
TI  - Detection of membrane and soluble interleukin-6 receptor in lymphoid
      malignancies.
AB  - We studied the membrane expression of the gp80 chain of IL-6 receptor (IL-6R) by
      quantitative flow cytometry in chronic lymphocytic leukaemia (CLL) and leukaemic
      centrocytic lymphoma using a panel of seven monoclonal antibodies. IL-6R was
      detected in 18/26 CLL cases and 4/7 lymphoma cases, with a mean antigen density <
      3000 molecules/cell. Multiple labelling experiments confirmed the IL-6R
      expression by neoplastic cells. Specific mRNA was found by RT-PCR in neoplastic
      cells. A specific ELISA test was designed using two anti-IL-6 receptor MAbs to
      measure the serum soluble IL-6R (sIL-6R) in CLL (n = 48). B-cell non-Hodgkin's
      lymphoma (NHL; n = 40), and monoclonal gammopathy (MG; n = 32). SIL-6R was higher
      in CLL (170 +/- 12.6 ng/ml) in NHL (160 +/- 12 ng/ml) and MG patients (183 +/- 23
      ng/ml) than in age-matched controls (100 +/- 5.6 ng/ml; P < 0.001) and higher in
      high-grade than low-grade NHL. No correlation was noted with a previous
      treatment. Among CLL cases the patients classified as stage B according to the
      Binet's staging of the disease had the highest sIL-6R values, thus suggesting a
      link with tumour cell mass.

PMID- 8547133
TI  - Combined cytogenetic, FISH and molecular analysis in acute promyelocytic
      leukaemia at diagnosis and in complete remission.
AB  - This study reports the results of a simultaneous application of cytogenetic
      fluorescence in situ hybridization (FISH) and molecular analysis (RT-PCR) in 28
      APL cases (23 M3 and five M3v; 26 studied at diagnosis and two at relapse). FISH
      on metaphases identified the t(15;17) in all cases who were positive for the
      PML/RAR alpha transcript by RT-PCR. Conventional cytogenetics revealed the
      t(15;17) in only 68% of cases. However, it enabled the detection of additional
      chromosome changes in five cases, three of whom were M3v. 11 patients were also
      investigated during complete remission (CR) by both FISH and RT-PCR, in order to
      evaluate residual disease; the duration of CR at the time of analysis ranged
      between 1 and 16 months, with three patients being studied twice. Comparison of
      RT-PCR and FISH results showed a very good correlation. In fact, of the 10
      samples which were RT-PCR positive for residual disease, all were also recognized
      by interphase FISH, and eight were positive by metaphase FISH. Of the three
      samples negative at RT-PCR, all were also negative at the interphase FISH. The
      results of this study indicate that: (a) the t(15;17) is present in all cases
      positive for the PML/RAR alpha rearrangement, thus in virtually all true APLs;
      (b) standard cytogenetics, capable of unravelling the t(15;17) in only 68% of
      cases, enables recognition of additional chromosome changes of potential clinical
      and prognostic significance; (c) FISH on interphase nuclei is a reliable tool for
      the monitoring of residual disease, with a sensitivity greater than that of FISH
      on metaphase cells and superimposable to that of RT-PCR.

PMID- 8547134
TI  - Isodicentric (X)(q13) in haematological malignancies: presentation of five new
      cases, application of fluorescence in situ hybridization (FISH) and review of the
      literature.
AB  - Idic(X)(q13) represents a rare but recurrent chromosomal abnormality in
      haematological malignancies. We present five new cases characterized by this
      particular aberration and review the literature on this subject. The patients
      were elderly females with a diagnosis of refractory anaemia (1/5), refractory
      anaemia with ringed sideroblasts (2/5), chronic myelomonocytic leukaemia (1/5),
      and Philadelphia chromosome-negative chronic myeloid leukaemia (1/5). Three out
      of the five patients demonstrated an increased proportion of bone marrow ringed
      sideroblasts. After a follow-up period of 30-57 months all patients but one are
      alive. Idic(X)(q13) always occurred as the sole chromosomal abnormality, either
      in one or in two copies. We confirmed the dicentric nature of the aberration by
      fluorescence in situ hybridization (FISH) on metaphases as well as interphase
      nuclei using an X-chromosome-specific alpha-satellite probe, and performed
      chromosome painting to visualize possible additional chromosomal changes
      involving the X chromosomes. Our findings and the data of 17 previously published
      cases indicate that idic(X)(q13): (1) may play a significant pathogenetic role in
      haematological malignancies affecting exclusively females and deriving
      predominantly from early progenitor cells; (2) is frequently associated with a
      pathological iron accumulation; (3) indicates a variable prognosis.

PMID- 8547135
TI  - Disappearance of AML1-MTG8(ETO) fusion transcript in acute myeloid leukaemia
      patients with t(8;21) in long-term remission.
AB  - In a study of 23 patients with t(8;21)-associated acute myeloid leukaemia the
      AML1-MTG8 fusion transcript was present in the majority of serial samples
      obtained from 17 patients followed for up to 34 months after diagnosis, but was
      absent in samples from all six patients who had been in continuous complete
      remission for 61 months after allogeneic bone marrow transplantation (BMT), or
      for 52, 53, 123, 182 and 198 months, respectively, after courses of intensive
      chemotherapy. Previous studies showed that the AML1-MTG8 fusion transcript was
      present in most patients with this type of translocation in long-term remission.
      Our results indicate that blood cells of patients with t(8;21) in remission of
      over 10 years may not show the AML1-MTG8 fusion transcript, and that those of
      patients who have undergone allogeneic BMT or intensive chemotherapy may become
      fusion transcript-negative much earlier. Our study suggests that leukaemic cells
      with the AML1-MTG8 fusion transcript may survive for some time after courses of
      chemotherapy or BMT, but that they may eventually be eradicated by immunologic
      and other antileukaemic mechanisms.

PMID- 8547136
TI  - Expression of the leucocyte common antigen (LCA, CD45) isoforms RA and RO in
      acute haematological malignancies: possible relevance in the definition of new
      overlap points between normal and leukaemic haemopoiesis.
AB  - The membrane expression of CD45RA and CD45RO on fresh leukaemic cells taken from
      529 cases of acute haemopoietic malignancies, including 117 B-origin acute
      lymphoblastic leukaemia (B-origin ALL), 37 T-origin acute lymphoblastic leukaemia
      (T-origin ALL0, 297 de novo acute myeloid leukaemia (AML), 42 refractory anaemia
      with excess of blasts in transformation (RAEB-T) and 36 myeloid blastic phase of
      chronic myelogenous leukaemia (CML-BP-my), was analysed. B-origin ALLs were
      characterized by the lack of the RO isoform along with the consistent presence of
      RA. Conversely, a differential expression of the two isoforms was detected in
      different subsets of T-origin ALL, in that T-stem cell leukaemias (T-SCL: CD7+,
      CD4-, CD8-, CD1-) preferentially expressed CD45RA whereas conventional T-acute
      lymphoblastic leukaemias (T-ALL: CD7+, CD4+ and/or CD8+ and/or CD1+) were
      consistently marked by CD45RO. Within myeloid malignancies, most of AMLs
      displayed CD45RA, while a substantial group of CML-BP-my preferentially exhibited
      CD45RO. As a general rule, a reciprocal exclusion of the two isoforms was
      observed in AML as well as in ALL. Nevertheless, a frequent coexpression of
      CD45RA and CD45RO was observed in CD14+ AML. In vitro treatment with all-trans
      retinoic acid (ATRA) was able to promote a switch from CD45RA to CD45RO
      expression in 27 de novo AML, independently from morphological subtyping. To our
      knowledge, this is the first report on CD45 isoform expression in a large series
      of patients with acute leukaemia. The knowledge of the differential expression of
      CD45RA and CD45RO can ameliorate our classificative approach to haematological
      malignancies, as well as disclose new multiple overlap points between normal and
      leukaemic cell differentiation.

PMID- 8547137
TI  - Effects of homo-aza-steroids on acute non-lymphocytic leukaemia cell
      proliferation in vitro.
AB  - Homo-aza-steroids (modified steroid molecules) in their esterified forms have
      been used extensively as carrier molecules of alkylating agents against several
      neoplastic malignancies in vivo and in vitro. We studied the effects of two homo
      aza-steroid carrier molecules alone, namely 3 beta-hydroxy-13 alpha-amino-13,17
      seco-5 alpha-androstan-17-oic-13, 17-lactam (compound 1) and 13 alpha-amino-13,17
      seco-1,3,5-estratrien-17-oic- 13,17-lactam (compound 2), on human acute non
      lymphocytic leukaemia cell proliferation in vitro. We used peripheral blood
      samples from 27 untreated ANLL patients (eight M1, four M2, two M3, six M4, three
      M5a, two M5b and two M6, according to FAB criteria). Proliferative activity was
      estimated by using thymidine uptake and the percentage of cells in metaphase in
      24, 48 and 72 h of culture. Exposure of human leukaemic blasts with either of the
      two compounds resulted in enhanced cell proliferation in M1, M2, M4, M6 and M5a
      (only by compound 2) cases, whereas there was no significant effect in the M3 and
      M5b cases. Our results indicate that the two compounds tested exhibit stimulatory
      effect on cell proliferation, particularly in blast cells possessing a relatively
      smaller degree of differentiation (M1 and M6 cases exhibiting CD34 and CD7).
      Further research is needed to study the cell growth effect and the therapeutic
      potential of these steroid molecules in human blood malignancies in vitro and in
      vivo.

PMID- 8547138
TI  - Preferred usage of specific immunoglobulin gene segments in chronic lymphocytic
      leukaemia cells of three HLA-identical sisters.
AB  - We report three family members, including a set of identical twins, who developed
      CD5 positive B-CLL. The patients are female Ashkenazi Jews sharing an identical
      HLA phenotype. Two of the HLA loci (B35 and Cw4) were common with those already
      described as being shared by Ashkenazi Jews with an increased incidence of CLL.
      The rearranged immunoglobulin genes of the malignant cells of all three patients
      were found to express genetically related VH regions belonging to the VH3
      subgroup, and chromosomal studies suggest a process of clonal evolution in one of
      the twins.

PMID- 8547139
TI  - Distribution of Kaposi's sarcoma herpesvirus sequences among lymphoid
      malignancies in Italy and Spain.
AB  - In this study we have tested the distribution of Kaposi's sarcoma herpesvirus
      (KSHV) DNA sequences throughout the spectrum of lymphoid neoplasia in Italy and
      Spain. 180 cases of lymphoid malignancies representative of the major histologic
      and immunophenotypic categories of B- and T-cell tumours were analysed by means
      of a polymerase chain reaction-based assay. KSHV sequences were consistently
      absent in all categories of lymphoid malignancies studied, with the exception of
      a subset of B-cell non-Hodgkin's lymphomas localizing in the pleural, pericardial
      or peritoneal cavities, and fulfilling the diagnostic criteria of body-cavity
      based lymphoma. The selective and consistent association of KSHV sequences with
      cases of body-cavity-based lymphoma throughout the spectrum of lymphoid neoplasms
      suggests that KSHV may be involved in the pathogenesis of this peculiar type of
      lymphoid malignancy.

PMID- 8547140
TI  - Absence of N-RAS point mutations in peripheral blood cells of patients with
      aplastic anaemia and paroxysmal nocturnal haemoglobinurea.
AB  - The myelodysplastic syndromes (MDS) have a significant frequency of evolution
      into acute myeloid leukaemia (AML). Approximately 30% of MDS patients show
      activating mutations of the N-RAS proto-oncogene, and these patients are at
      increased risk of leukaemic evolution. Long-term survivors of aplastic anaemia
      (AA) and paroxysmal nocturnal haemoglobinurea (PNH) are also at significant risk
      of developing AML. We have screened peripheral blood DNA from 42 AA patients and
      15 PNH patients for the presence of N-RAS point mutations. No mutations were
      detected in these samples, indicating that the mechanisms of evolution into AML
      may be different from those in MDS.

PMID- 8547141
TI  - t(8;21) detection by RT-PCR: an improved primer set convenient for the routine
      laboratory.
AB  - A new set of primers to detect t(8;21) by RT-PCR have been designed. These
      primers give a more specific PCR amplification than the original primers and can
      be used with a cycling regime that is already in use for a wide range of other
      PCR methods in the routine haematology laboratory.

PMID- 8547142
TI  - Expression of the human OX40 (hOX40) antigen in normal and neoplastic tissues.
AB  - The Ber-ACT35 mAb was raised against the human T-cell lymphotrophic virus (HTLV)
      1-transformed, CD4+ HUT 102 cell line and recognizes the human homologue of the
      OX40 (hOX40) antigen. The analysis of the expression of hOX40 by
      immunohistochemical techniques in malignant lymphomas, carcinomas and non
      malignant tissues of different organs shows that hOX40 expression was almost
      completely restricted to T lymphocytes. Besides T cells only a small
      subpopulation of macrophages in Langerhans' cell histiocytosis and a few blasts
      in B-cell non-Hodgkin's lymphoma (B-NHL) revealed a faint immunostaining with the
      Ber-ACT35 mAb. Furthermore, most of the hOX40+ T-cells are CD4+.

PMID- 8547143
TI  - BCR-ABL rearrangement and 'variant' Philadelphia chromosome in de novo acute
      myelogenous leukaemia FAB subtype M1.
AB  - We report a case of de novo acute myelogenous leukaemia FAB subtype M1 that
      presents a cytogenetic complex translocation between chromosomes 7, 9 and 22,
      producing a 'variant' Philadelphia chromosome. Molecular analysis revealed a BCR
      ABL rearrangement involving exons b3 and a2 (b3a2). Haematological parameters and
      genetic analysis again raise the problem of the true nature of this disease,
      which is briefly discussed.

PMID- 8547144
TI  - Peripheral primitive neuroectodermal tumour after allogeneic bone marrow
      transplantation.
AB  - We report a case of peripheral primitive neuroectodermal tumour (PNET) in a 36
      year-old man who 10 years earlier received an allogeneic bone marrow
      transplantation (BMT) for a non-Hodgkin's lymphoma. Immunohistochemistry proved
      definitive elimination of a relapse of the original disease and confirmed the
      diagnosis of PNET. The role of total body irradiation pre-BMT in the genesis of
      this secondary tumour is discussed. The importance of registering secondary
      malignant solid tumours after BMT is emphasized. To our knowledge, an Ewing
      family tumour following BMT has not previously been reported.

PMID- 8547145
TI  - EBV-associated lymphoproliferative syndrome with a distinct 69 base-pair deletion
      in the LMP-1 oncogene.
AB  - We describe an immunocompetent 12-year-old boy with chronic EBV infection and
      lymphoid interstitial pneumonitis. Lymph node biopsies showed effacement of the
      architecture with polymorphic cellular infiltrates, consisting predominantly of T
      cells and natural killer cells. No clonal rearrangement of TCR or immunoglobulin
      genes was seen. DNA was extracted from hilar lymph nodes; sequencing of the
      carboxy terminal region of the latent membrane protein 1 (LMP-1) oncogene
      revealed a 69 base-pair deletion and four point mutations. Immunosuppressive
      treatment with prednisone and cyclosporine reversed the lymphadenopathy.

PMID- 8547146
TI  - Expression of lymphoid-associated antigens in mast cells: report of a case of
      systemic mast cell disease.
AB  - In this study the expression of 'classically' considered lymphoid-associated
      antigens (CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, and CD22) was explored
      both in peripheral blood (PB) and bone marrow (BM) mast cells (MC) in a case of
      systemic mast cell disease (SMCD) by means of using multiple stainings and a
      direct immunofluorescence technique. CD2 and CD22 were expressed in both PB and
      BM MC, all the remaining lymphoid-associated markers were negative. Our results
      suggest that the reactivity for both CD2 and CD22 in PB and BM MC would be
      aberrant.

PMID- 8547147
TI  - Fab-mediated binding of glycoprotein Ib/IX and IIb/IIIa specific antibodies in
      chronic idiopathic thrombocytopenic purpura.
AB  - The antibody domain responsible for the interactions between platelet
      glycoproteins (GP) and serum IgG autoantibodies in patients with chronic
      idiopathic thrombocytopenic purpura (ITP) was studied. Sera from nine non
      transfused ITP patients and 20 normal controls and a serum containing an anti
      PlA1 antibody were employed. Serum, purified IgG and F(ab')2 fragments were
      prepared and their binding to platelet GPIb/IX and GPIIb/IIIa were analysed using
      a modified MAIPA assay and an antigen capture ELISA. In all experiments most of
      the autoantibodies studied behaved identically to the anti-PlA1 antibody in that
      the IgG-F(ab')2 fragments retained their ability to bind to the respective
      glycoprotein. Substituting the enzyme-conjugated secondary antibody (Fab
      specific), in the MAIPA assay, with an Fc specific antibody removed all
      reactivities observed against platelet GPs, produced by IgG-F(ab')2 fragments.
      Furthermore, in an antigen-capture ELISA, IgG autoantibodies against platelet
      GPIb/IX and/or GPIIb/IIIa were blocked preferentially by pre-incubating the ITP
      sera with a goat anti-human IgG (F(ab')2 specific) antibody, but not with an anti
      Fc antibody. We conclude that these ITP patients produced antibodies specific for
      platelet GPIb/IX and/or GPIIb/IIIa, and that the autoantibody-platelet
      interaction was mediated by the classic Fab binding.

PMID- 8547148
TI  - A human monoclonal antibody obtained from EBV-transformed B cells with
      specificity for myosin.
AB  - We describe the preparation of a stable human lymphoblastoid cell line obtained
      during ex vivo studies in which peripheral blood lymphocytes of a Glanzmann's
      thrombasthenia patient were transformed with Epstein-Barr virus. Somatic hybrids
      secreted an IgM monoclonal antibody (B7) that reacted with the myosin heavy chain
      of human platelets by immunoblotting. Flow cytometry showed that B7 barely
      recognized unstimulated intact platelets, but bound abundantly after
      permeabilization of fixed cells with Triton X-100. The reactivity of the antibody
      on thin sections of human myocardium and aorta was studied by
      immunohistochemistry. B7 specifically stained myosin of myocytes, but there was
      no labelling of aortic smooth muscle cells. The epitope was conserved in cardiac
      or skeletal myosin prepared from pig or rabbit. Measurement of the dissociation
      constant in a competitive ELISA showed that B7 bound with high affinity (10(-8)
      M). Purified Fab fragments retained their ability to bind to myosin, suggesting
      that B7 may be useful in the imaging of myocardial necrosis after myocardial
      infarction, myocarditis, cardiac drug toxicosis or graft rejection. This work
      also shows that EBV transformation of B cells may uncover naturally occurring
      autoantibodies which under normal circumstances are inhibited by the immune
      surveillance system.

PMID- 8547149
TI  - Induction of tissue factor expression in human monocyte/endothelium cocultures.
AB  - Induction of tissue factor (TF) expression on monocytes and endothelial cells is
      central to the development of septic coagulopathy. Serum concentrations of
      endotoxin in septic patients who develop disseminated intravascular coagulation
      (DIC) do not, however, reach the levels that would directly stimulate TF
      expression on either monocytes or endothelium. We show, using an in vitro
      coculture system, that the interaction of monocytes with endothelium induces the
      expression of significant levels of TF. Unstimulated cocultures of monocytes (2 x
      10(4)/well) and endothelial cells (2 x 10(4)/well) produced 35.3 +/- 8.5 mU of
      PCA/well, representing a 5-fold increase over the combined PCA of each cell type
      cultured alone (7.1 +/- 1.5 mU, n = 6, P < 0.001). Significant enhancement was
      also found in the presence of low concentrations of LPS. Induction of TF protein
      was confirmed by Western blotting. Fixation of monocytes with paraformaldehyde
      completely abolished TF induction in cocultures, whereas fixation of endothelium
      had no effect, suggesting that TF induction occurred in monocytes rather than
      endothelial cells. Induction of TF in cocultures could be further augmented by
      preincubating the endothelial cells with IFN-gamma. When endothelium was
      prestimulated with 500 U/ml IFN-gamma there was 142 +/- 11% increase over
      unstimulated cocultures (n = 5, P < 0.01). TF induction was inhibited by 32 +/-
      6% in the presence of anti-ICAM-1 mAb (n = 5, P < 0.01). Our results suggest that
      monocyte interactions with vascular endothelium, regulated by inflammatory
      cytokines, and mediated by adhesive ligand binding, leads to the induction of
      functional monocyte TF protein, which may be responsible for the initiation of
      DIC in sepsis.

PMID- 8547150
TI  - Glycoprotein IIb/IIIa autoantigenic repertoire in chronic idiopathic
      thrombocytopenic purpura.
AB  - The objective of the present study was to further disclose the autoantigenic
      repertoire carried by the platelet glycoprotein (GP) IIb/IIIa complex. IgG
      F(ab')2 fragments were prepared from two prototype ITP patients, and their
      ability to block the binding of GPIIb/IIIa reactive antibodies derived from other
      patients with ITP was evaluated using a modified MAIPA asay; a PlA1 alloantiserum
      and 20 normal sera were included as controls. It was found that the two prototype
      IgG-F(ab')2 fragments were each able to significantly block the binding of serum
      IgG to GPIIb/IIa in six (55%) and seven (64%) out of 11 patients with chronic
      ITP, respectively. No significant blocking effect was observed for IgG-F(ab')2
      fragments prepared from normal subjects. Also, the binding of the PlA1
      alloantiserum to its epitope on GPIIIa was not affected by any of the blocking
      IgG-F(ab')2 fragments exploited in the study. These data substantiate that in
      chronic ITP at least half of the GPIIb/IIIa reactive sera bind to homogenous
      autoepitopes.

PMID- 8547151
TI  - Heterogenous inhibition of platelet aggregation by monoclonal antibodies binding
      to multiple sites on GPIIIa.
AB  - Six monoclonal IgG1-k antibodies (LK2, LK3r, LK4-55, LK5, LK6-55, LK7r) were
      raised against platelet membrane GPIIIa in order to study the structure-function
      relationship of this molecule. Antibodies were selected on their ability to react
      with GPIIIa by ELISA on adherent platelets, by immunoblot on platelet lysates and
      by fluorescence flow cytometry on intact platelets. Fluorescence reactivity
      varied from 3- to 202-fold greater than isotype control fluorescence. Two MoAbs
      reacted on immunoblot under reduced conditions (LK7r and LK3r). Two reacted with
      a 55 kD chymotrypsin/subtilisin digest of GPIIIa which is likely to exclude amino
      acids 121-348 (LK4-55 and LK6-55). Four of the MoAbs (LK5, LK3r, LK2 and LK4-55)
      inhibited tyrosine phosphorylation of one to four distinct bands on immunoblot.
      LK4-55 reacted with an N-terminal 66 amino acid fusion protein of GPIIIa near the
      PLA epitope (Leu 33). LK7r reacted with a 212-222 peptide reported to be an RGD
      fibrinogen binding site. LK2 reacted near a disintegrin-RGD binding site. Except
      for LK5, all inhibited ADP, collagen and thrombin-induced platelet aggregation in
      a heterogeneous fashion. Percentage inhibition of 125I-fibrinogen binding to
      platelets varied from 18% to 98%. No correlation was noted between inhibition of
      fibrinogen binding, location of MoAb binding on GPIIIa, reactivity of MoAb
      binding with GPIIIa, inhibition of thrombin-induced tyrosine phosphorylation or
      inhibition of platelet aggregation induced by ADP, collagen or thrombin. Thus
      MoAbs, binding to platelet GPIIIa at different sites, inhibit platelet
      aggregation in a heterogeneous manner.

PMID- 8547153
TI  - Blood platelet heterogeneity: a functional hierarchy in the platelet population.
AB  - The platelet population in man and rat can be divided into two classes of about
      equal size based on the presence/absence of a p-nitrophenylphosphatase, which
      probably is a phosphotyrosine phosphatase (PTPase). Phosphorylation of tyrosines
      on several platelet proteins is implicated in platelet activation, and I carried
      out in vitro and in vivo experiments on rats to determine whether PTPase positive
      and negative platelets differed in their reaction time. I used adhesion to
      collagen in vitro and in vivo (longitudinal slits in aorta and vena portae) and
      platelet aggregates in clots formed in vivo. I present evidence that PTPase
      negative platelets react the fastest, most conspicuously seen in the arterial
      bleeding under high flow conditions, where the first platelets to respond and
      adhere are predominantly PTPase negative.

PMID- 8547152
TI  - Effects of different amino-acid substitutions in the leucine 694-proline 708
      segment of recombinant von Willebrand factor.
AB  - Type 2B von Willebrand disease (vWD) is characterized by an increased affinity of
      von Willebrand factor (vWF) for binding to platelet glycoprotein Ib (GpIb). Most
      type 2B candidate mutations are clustered in the 509-695 disulphide loop but
      three of them (H505D, L697V and A698V) are outside this loop. We confirm here
      that the A698V mutation is a type 2B mutation by its expression in Cos-7 cells.
      As the L697V and A698V type 2B mutations both induce the presence of a valine
      residue in the 694-708 sequence, we created and expressed different mutated
      recombinant vWFs (rvWFs), in substituting the other leucine and alanine residues
      of this sequence (at positions 694, 701 and 706) into valine resides. V694rvWF
      and V706rvWF displayed decreased ristocetin-induced GpIb binding showing that it
      is not always the presence of a valine residue that may explain the increased
      affinity of type 2B vWF for GpIb. We also compared the interaction with platelets
      of V697rvWF and V698rvWF to those obtained with rvWFs reproducing two prevalent
      type 2B mutations located in the loop (R543W and V553M). We show that the two
      mutations located in the loop are more reactive than the two mutations identified
      outside the loop.

PMID- 8547154
TI  - Quality evaluation of 10 years patient records in forensic odontology.
AB  - In forensic odontology, accurate detailed and complete recording of ante-mortem
      information is essential as the basis for odontological identification. Earlier
      studies on malpractice cases in Sweden indicated that the quality of the
      recording procedure was not always acceptable. Therefore, the aim of this
      retrospective study was to investigate the quality of ante-mortem records and its
      possible implications for identification work. All forensic odontology cases
      referred to the Department of Forensic Medicine in Goteborg between 1983 and 1992
      were studied with regard to the instructions for dental records from the National
      Board of Health and Welfare. Information on dental characteristics, normal
      anatomical findings and restorative treatment was complete in 43 (68%) of the
      cases, incomplete in 17 (27%) and missing in 3 (5%). Registration of previous
      therapy was missing in about 75 (94%) of the records. It was possible to identify
      patient radiographs in only 16 of the 40 records where radiographs were
      available. In spite of this, the inaccuracies in the records did not seem to
      hamper the identification procedures in this study which could be explained by
      the character of the cases and the availability of medical and circumstantial
      information.

PMID- 8547155
TI  - A specific immunoassay for the detection of flunitrazepam.
AB  - The development of an immunochemical procedure for the determination of
      flunitrazepam in whole blood is described. Flunitrazepam was derivatized in
      position 3 of the benzodiazepine ring to a hapten which was coupled to a carrier
      protein. To obtain antibodies, rabbits were immunized with these immunogens and
      the collected antisera were tested in a heterogeneous, competitive RIA. The
      antibodies showed a very specific reaction with flunitrazepam and hardly any
      cross-reactivity with related 1,4-benzodiazepines. Because of its high
      specificity the antiserum has the advantage of a definite determination of low
      levels of flunitrazepam without the risk of false-negative results obtained by
      using the commercially available group-specific test systems. The drug was
      extracted from whole blood in a simple batch process with a polystyrene
      suspension and the extracts were measured by RIA. The advantages of an
      immunochemical system, such as short analysis time and simple sample preparation,
      and the exactness of a drug-specific method are combined in this procedure, which
      allowed the specific and very sensitive determination of flunitrazepam in the low
      therapeutic range.

PMID- 8547156
TI  - Frequency profiles of 3 STRs in a Turkish population.
AB  - Population genetic studies were carried out on Caucasians from southern Turkey (n
      = 204 individuals) using the short tandem repeat (STR) systems HumTHO1, HumVWA
      and HumACTBP2. After electrophoresis in polyacrylamide gels, 6 alleles could be
      identified for HumTHOI, 7 alleles for VWA and 26 alleles for ACTBP2. No
      significant deviations from Hardy-Weinberg equilibrium could be observed.

PMID- 8547157
TI  - Genetic polymorphism of the H1 subunit of inter-alpha-trypsin inhibitor.
AB  - Inter-alpha-trypsin inhibitor (ITI) consists of 3 subunits (H1, H2 and L) which
      are encoded by 3 distinct genes. We attempted to prepare the subunit-specific
      monoclonal antibodies to identify the subunit carrying ITI polymorphism. Three
      monoclonal antibodies which were specific against each of these 3 subunits (ITI
      H1, ITI H2 and ITI L) were selected. ITI types could be detected by anti ITI H1
      antibody, but not by anti ITI H2 or anti ITI L antibodies. From the result, it
      was proved that ITI polymorphism originates from the ITI H1 gene products,
      therefore we propose to call this system ITI H1 polymorphism.

PMID- 8547158
TI  - Terminal burrowing behaviour--a phenomenon of lethal hypothermia.

PMID- 8547159
TI  - Penetrating gunshots to the head and lack of immediate incapacitation. I. Wound
      ballistics and mechanisms of incapacitation.
AB  - There are two distinct mechanisms of ballistic injury. Crushing of tissue
      resulting in a permanent tract is the primary factor in wounding of most tissues
      and most body regions. Temporary cavitation causes radial tissue displacement and
      subsequent shearing, compression and especially stretching of tissue analogous to
      blunt trauma. In contrast to the effect in elastic tissue, temporary cavitation
      can contribute substantially to wounding of inelastic tissue, such as the brain.
      This is the case in penetrating gunshot wounds to the head. Additionally, the
      penetration of the bony cranium can produce secondary missiles in the form of
      bone or bullet fragments and a tendency of the bullet to deformation and early
      yaw. Most important, wounding resulting from temporary cavitation is greatly
      augmented by the confined space provided by the unyielding walls of the skull.
      Bone contact and enhanced effects of temporary cavitation result in an enlarged
      zone of disintegrated tissue and in high intracranial peak pressures.
      Morphological signs of powerful intracranial pressure effects are cortical
      contusion zones, indirect skull fractures and perivascular haemorrhages remote
      from the tract. Depending on ballistic and anatomical parameters, the
      intracranial effect varies from slightly more severe injury than in isolated soft
      tissue to an "explosive" type of injury with comminuted fractures of the skull
      and laceration of the brain. Incapacitation is the physiologically based
      inability to perform complex and longer lasting movements independent of
      consciousness or intention. Immediate incapacitation is possible following cranio
      cerebral gunshot wounds or wounds that disrupt the upper cervical spinal cord
      only. Rapid incapacitation can be produced by massive bleeding from major vessels
      or the heart. Immediate incapacitation is the result of primary intracranial
      effects of the bullet. A mechanism similar to commotion cerebri applied
      extracranially does not exist in cases of penetrating gunshot wounds to the head.

PMID- 8547160
TI  - Terminal ballistics of 7.62 mm NATO bullets: experiments in ordnance gelatin.
AB  - Military rifle bullets are assumed to tumble 180 degrees in the target and end up
      facing backwards, but intact. It has been claimed, however, that a German version
      of the 7.62 mm x 51 (7.62 mm NATO) bullet may fragment at ranges up to 100 m. A
      lack of strength in the jacket, causing it to break at the cannelure when hitting
      the target at high impact velocity, has been held responsible for this behaviour.
      The Danish Armed Forces use a 7.62 mm x 51 bullet, produced by
      Ammunitionsarsenalet (AMA), which is similar in design. Since the legality of
      this and similar bullets may be questioned in view of the Hague Declaration of
      1899, we decided to supplement an investigation of actual fatal cases with an
      investigation using ordnance gelatin. In order to compare various makes of
      bullets on an equal basis, they were fired into ordnance gelatin at various
      ranges and, consequently with various impact velocities. Bullets manufactured by
      the US Government, Bofors (Sweden), Raufoss (Norway) and AMA were used. The AMA
      bullet M/75 used previously was found to fragment at ranges up to approx. 100 m,
      corresponding to impact velocities of approx. 715 m/sec, while all the other 3
      types of bullets were intact at ranges down to 2.5 m, corresponding to impact
      velocities of approx. 810 m/sec. The final prototype of an AMA bullet to answer
      this criticism proved capable of withstanding fragmentation as well as the
      foreign makes previously tested. It will enter series production in late 1995.

PMID- 8547161
TI  - Validation of mitochondrial DNA sequencing for forensic casework analysis.
AB  - Two sets of studies were performed to evaluate the forensic utility of sequencing
      human mitochondrial DNA (mtDNA) derived from various tissues and amplified by the
      polymerase chain reaction (PCR). Sequencing was performed on a Perkin
      Elmer/Applied Biosystems Division (PE/ABD) automated DNA sequencer (model 373A).
      The first set of experiments included typical validation studies that had
      previously been conducted on forensic DNA markers, such as: chemical contaminant
      effects on DNA from blood and semen and the effect of typing DNA extracted from
      body fluid samples deposited on various substrates. A second set of experiments
      was performed strictly on human hair shafts. These studies included typing mtDNA
      from hairs that were: (1) from different body areas, (2) chemically treated, (3)
      from deceased individuals, and (4) deliberately contaminated with various body
      fluids. The data confirm that PCR-based mtDNA typing by direct automated
      sequencing is a valid and reliable means of forensic identification.

PMID- 8547162
TI  - Evaluation of an ACTBP2 ladder composed of 26 sequenced alleles.
AB  - A total of 90 alleles found in white Caucasians from North-West Germany were
      sequenced and 26 alleles chosen to construct a uniform and reliable allelic
      ladder for the STR system ACTBP2 (SE33). In addition 3 new aspects concerning the
      sequence structure were observed. Population studies were carried out on white
      Caucasians (n = 278) from North-West Germany using the new improved ladder. A
      total of 24 alleles and 14 "interalleles" were found and reproducible results
      obtained. No significant deviation from Hardy-Weinberg-equilibrium could be
      observed.

PMID- 8547163
TI  - GEDNAP IV and V. The 4th and 5th Stain Blind Trials using DNA technology.
AB  - In the collaborative exercise GEDNAP IV one EDTA blood sample (2 ml) and 5
      bloodstains (0.5 ml on cotton) were investigated and in GEDNAP V, a total of 8
      bloodstains (0.5 ml on cotton), including 2 mixed bloodstains. DNA typing was
      carried out using the RFLP systems YNH24/Hinf I and MS43a/Hinf I and the PCR
      systems HLA DQ alpha, D1S80, ApoB and YNZ22. In both exercises approximately 20
      laboratories obtained results using the RFLP systems. Of the PCR systems, D1S80
      was the most commonly used (14 labs in GEDNAP IV; 18 labs in GEDNAP V). The
      interlaboratory standard deviation for YNH24 in both exercises was approx. 0.6%,
      for MS43a 0.7-2.2% (GEDNAP IV) and 0.4-1.4% (GEDNAP V), depending on the fragment
      size. The fragment size calculation performed in each laboratory yielded a
      standard deviation twice that obtained when the fragment size calculation was
      performed centrally (IfR, Munster). In GEDNAP III, a system-specific corridor was
      developed to define the limits of deviation; this was modified for the present
      study by combining the fragment size ranges of YNH24 and MS43a. In both studies a
      subgroup of laboratories was involved in preliminary exercises using three PCR
      VNTRs and the system HLA DQ alpha. Owing to the substantial variation in
      experience of the participating laboratories with PCR typing the results obtained
      in these two studies do not fulfil the basic quality criteria of the GEDNAP
      studies.

PMID- 8547164
TI  - Infections of the upper respiratory tract in cases of sudden infant death.
AB  - The nasal cavities were examined in 56 cases of sudden infant death syndrome
      (SIDS) and 26 control cases and the following criteria were compared:
      inflammatory infiltration of the nasal mucosa (SIDS 59%--controls 65%; P =
      0.577), diapedesis of inflammatory cells (SIDS 38%--controls 42%; P = 0.678),
      epithelial desquamation (SIDS 62%--controls 85%; P = 0.043); hyperemia (SIDS 66%-
      controls 65%; P = 0.951) and hypersecretion of the seromucous glands (SIDS 55%-
      controls 69%; P = 0.233). Only epithelial desquamation was found significantly
      more often in the controls than in SIDS cases, but these alterations are
      unspecific and are influenced by the postmortem interval. The intensity of
      rhinitis was not different between the SIDS and control groups. The frequency of
      rhinitis is therefore not specific for the sudden infant death syndrome, and
      seems to be merely a result of the high incidence of upper respiratory tract
      infections in this age group. We speculate, however, that infections of the nose
      in conjunction with other factors, such as prone position, covering of the head,
      hyperthermia, parental smoking and immaturity of the central nervous system,
      could play a role in the pathogenesis of the sudden infant death syndrome.

PMID- 8547165
TI  - Observation of null alleles apparently due to deletions.
AB  - After examining 2 paternity cases in 17 classical, 4 RFLP and 5 PCR-VNTR systems,
      isolated pseudo-exclusions were observed in the polymorphism D2S44 (YNH24). In
      both cases the "exclusions" were due to apparent opposite homozygosity. The
      application of different restriction enzymes, PCR amplification and varying
      electrophoretic conditions each led to an equivalent result of a 1-band-pattern
      with a mismatch between both father/child pairs. From these results the authors
      conclude that a complete or almost complete loss of the alleles is the most
      probable explanation.

PMID- 8547166
TI  - HumFES/FPS and HumF13B: Turkish and German population data.
AB  - The allele distribution of two STRs has been investigated in two populations,
      i.e. Turks (n = 203/200) and Germans (n = 414/402). The Turkish population showed
      11 alleles in HumFES/FPS and 6 alleles in HumF13B while the German population had
      9 (FES) and 8 (F13B) alleles respectively. Although the frequency profiles looked
      quite similar in both populations, there exist significant differences mainly due
      to alleles 8 and 10 (F13B) and allele 12 (FES). Four variant alleles have been
      sequenced and are described. Investigation of 368 (FES)/372 (F13B) meioses
      revealed no new mutations.

PMID- 8547167
TI  - The time-dependent appearance of black eyes.
AB  - The time-dependent appearance of hematomas of the eyelids was investigated in 484
      cases of head injury. In individuals with apparent signs of direct violence to
      the orbit or the nose, black eyes could be observed even without relevant post
      infliction intervals. Similarly, in victims with fractures at the anterior base
      of the skull hematomas of the eyelids were found even though death had occurred
      rapidly within less than 30 min after trauma. Black eyes that can be explained
      exclusively by a seepage of blood from frontal scalp wounds appeared
      approximately 4 h after wound infliction at the earliest, indicating a minimum
      post-infliction interval. Since hemorrhages of the eyelids can also be induced
      postmortem by direct violence to the orbit, particularly in cases with hypostasis
      of the face, the presence of black eyes seems not to be an unambiguous sign of
      vital trauma.

PMID- 8547168
TI  - Proceedings of the workshop on the molecular and cell biology of hydroxysteroid
      dehydrogenases. Hannover, Germany, 19-22 April 1995.

PMID- 8547169
TI  - Placental 11 beta-hydroxysteroid dehydrogenase and the programming of
      hypertension.
AB  - Excessive foetal exposure to glucocorticoids retards growth and "programmes"
      adult hypertension in rats. Placental 11 beta-hydroxysteroid dehydrogenase (11
      beta-HSD), which catalyses the conversion of corticosterone and cortisol to inert
      11 keto-products, normally protects the foetus from excess maternal
      glucocorticoids. In both rats and humans there is considerable natural variation
      in placental 11 beta-HSD, and enzyme activity correlates with birth weight.
      Moreover, inhibition of placental 11 beta-HSD in the rat reduces birth weight and
      produces hypertensive adult offspring, many months after prenatal treatment with
      enzyme inhibitors; these effects are dependent upon maternal adrenal products.
      These data suggest that placental 11 beta-HSD, by regulating foetal exposure to
      maternal glucocorticoids, crucially determines foeto-placental growth and the
      programming of hypertension. Maternal protein restriction during pregnancy also
      produces hypertensive offspring and selectively attenuates placental 11 beta-HSD
      activity. Thus, deficiency of the placental barrier to maternal glucocorticoids
      may represent a common pathway between the maternal environment and foeto
      placental programming of later disease. These data may, at least in part, explain
      the human epidemiological observations linking early life events to the risk of
      subsequent hypertension. The recent characterization, purification and cDNA
      cloning of a distinct human placental 11 beta-HSD (type 2) will aid the further
      study of these intriguing findings.

PMID- 8547170
TI  - The human 11 beta-hydroxysteroid dehydrogenase type II enzyme: comparisons with
      other species and localization to the distal nephron.
AB  - Effective glucocorticoid inactivation is currently thought to be an indispensable
      feature of mineralocorticoid target cells. The enzyme 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD) inactivates glucocorticoids and prevents them from
      binding to the non-selective mineralocorticoid receptor. In the kidney it is the
      NAD dependent high affinity isoform (11 beta-HSD2) which is thought to endow
      specificity on the receptor. The recent cloning of the human, sheep and rabbit 11
      beta-HSD2 enzymes permits a comparison of the enzyme from the three species.
      Human and rabbit enzymes are 87% identical and of similar length, while the human
      and sheep enzymes have only 75% identity. The last 12 residues in all three
      species were found to be highly divergent, but most of the ovine dishomology can
      be accounted for by the deletion of a single nucleotide toward the C-terminus of
      the protein resulting in a shift in reading frame generating a protein 27
      residues longer than the human isoform. Numerous other deletions were also
      observed in this region of the sheep cDNA sequence. Furthermore, the rabbit cDNA
      also displayed a large degree of dishomology with the human sequence a short
      distance downstream from the termination codon. Conserved overlapping cytoplasmic
      translocation signals were observed in all three species, suggesting a topology
      whereby the enzyme is anchored into the endoplasmic reticulum by multiple
      hydrophobic regions in the N-terminus and the bulk of the 11 beta-HSD2 peptide is
      sited in the cytoplasm. A polyclonal antibody generated against the C-terminus of
      human 11 beta-HSD2 was used to localize the enzyme within the kidney. A high
      level of immunoreactive was observed in distal tubules and collecting ducts,
      localizing the enzyme to the same part of the nephron as the mineralocorticoid
      receptor. Moderate levels of staining were also seen in vascular smooth muscle
      cells. These results support the notion that 11 beta-HSD2 is an autocrine
      protector of the mineralocorticoid receptor and that it plays an important role
      in cardiovascular homeostatic mechanisms.

PMID- 8547171
TI  - Type 2 11 beta-hydroxysteroid dehydrogenase in foetal and adult life.
AB  - Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyse the
      interconversion of active cortisol to inactive cortisone; 11 beta-HSD1 is a low
      affinity, NADP(H)-dependent dehydrogenase/oxo-reductase, and 11 beta-HSD2 a high
      affinity, NAD-dependent dehydrogenase. Because of the importance of 11 beta-HSD
      in regulating corticosteroid hormone action, we have analysed the distribution of
      the 11 beta-HSD isoforms in human adult and foetal tissues (including placenta),
      and, in addition have performed a series of substrate specificity studies on the
      novel, kidney 11 beta-HSD2 isoform. Using an RT-PCR approach, we failed to detect
      11 beta-HSD1 mRNA in any human mid-gestational foetal tissues. In contrast 11
      beta-HSD2 mRNA was present in foetal lung, adrenal, colon and kidney. In adult
      tissues 11 beta-HSD2 gene expression was confined to the mineralocorticoid target
      tissues, kidney and colon, whilst 11 beta-HSD1 was expressed predominantly in
      glucocorticoid target tissues, liver, lung, pituitary and cerebellum. In human
      kidney homogenates, 11-hydroxylated progesterone derivatives, glycyrrhetinic
      acid, corticosterone and the "end products" cortisone and 11
      dehydrocorticosterone were potent inhibitors of the NAD-dependent conversion of
      cortisol to cortisone. Finally high levels of 11 beta-HSD2 mRNA and activity were
      observed in term placentae, which correlated positively with foetal weight. The
      tissue-specific distribution of the 11 beta-HSD isoforms is in keeping with their
      differential roles, 11 beta-HSD1 regulating glucocorticoid hormone action and 11
      beta-HSD2 mineralocorticoid hormone action. The correlation of 11 beta-HSD2
      activity in the placenta with foetal weight suggests, in addition, a crucial role
      for this enzyme in foetal development, possibly in mediating ontogeny of the
      foetal hypothalamo-pituitary-adrenal axis.

PMID- 8547172
TI  - Analysis of the human gene encoding the kidney isozyme of 11 beta-hydroxysteroid
      dehydrogenase.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the conversion of
      cortisol to cortisone. This activity may be deficient in the syndrome of apparent
      mineralocorticoid excess (AME). 11 beta-HSD L (Type I), isolated from liver, is
      widely expressed and utilizes NADP+ as a cofactor. The gene for 11 beta-HSD L was
      found to be normal in patients of AME. A second isoform, 11 beta-HSD K (Type II),
      isolated from kidney, is more tissue specific in expression and utilizes NAD+ as
      a cofactor. The cDNA clone encoding 11 beta-HSD K was isolated from sheep kidney.
      The cDNA is 1.8 kb in length and encodes a protein of 404 amino acid residues
      with a predicted M(r) 43,953. The recombinant enzyme functions as an NAD(+)
      dependent 11 beta-dehydrogenase with very high affinity for steroids, but it has
      no detectable reductase activity. It is 37% identical in amino acid sequence to
      an NAD(+)-dependent isozyme of 17 beta-hydroxysteroid dehydrogenase. It is
      expressed at high levels in the kidney, placenta, adrenal and at lower levels in
      colon, stomach, heart and skin. The human 11 beta-HSD K gene consists of five
      exons spread over 6 kb. The nucleotide binding domain lies in the first and the
      second exon, and the catalytic domain in the fourth exon. The promoter for 11
      beta-HSD K gene lacks a TATA box and has a high GC base content, suggesting that
      the gene may be transcriptionally regulated by factors that recognize GC-rich
      sequences. Fluorescent in situ hybridization of metaphase chromosomes with a
      positive bacteriophage P1 genomic 11 beta-HSD K clone localized the gene to
      chromosome 16q22. In contrast, the 11 beta-HSD L gene is located on chromosome 1
      and contains 6 exons; the coding sequences of these genes are only 21% identical.
      Different transcriptional start sites are utilized in kidney and placenta.

PMID- 8547173
TI  - Expression and characterization of isoforms of 3 beta-hydroxysteroid
      dehydrogenase/delta 5-->4-isomerase in the hamster.
AB  - The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD)
      is essential for the production of all classes of steroid hormones. Multiple
      isozymes of this enzyme have been demonstrated in the kidney and liver of both
      the rat and the mouse, although the function of the enzyme in these tissues is
      unknown. We have characterized three isozymes of 3 beta-HSD expressed in various
      tissues of the hamster. Both western and northern blot analyses demonstrated very
      high levels of 3 beta-HSD in the adrenal, kidney and male liver. Conversely,
      there were extremely low levels of enzyme expression in the female liver. cDNA
      libraries prepared from RNA isolated from hamster adrenal, kidney and liver were
      screened with a full-length cDNA encoding human type 1 3 beta-HSD. Separate cDNAs
      encoding three isoforms of 3 beta-HSD were isolated from these libraries. To
      examine the properties of the isoforms, the cDNAs were ligated into expression
      vectors for over-expression in 293 human fetal kidney cells. The type 1 isoform,
      isolated from an adrenal cDNA library, was identified as a high-affinity 3 beta
      hydroxysteroid dehydrogenase. A separate isoform, designated type 2, was isolated
      from the kidney, and this was also a high-affinity dehydrogenase/isomerase. Two
      cDNAs were isolated from the liver, one identical in sequence to type 2 of the
      kidney, and a distinct cDNA encoding an isoform designated type 3. The type 3 3
      beta-HSD possessed no steroid dehydrogenase activity but was found to function as
      a 3-ketosteroid reductase. Thus male hamster liver expresses a high-affinity 3
      beta-HSD (type 2) and a 3-ketosteroid reductase (type 3), whereas the kidney of
      both sexes express the type 2 3 beta-HSD isoform. These differ from the type 1 3
      beta-HSD expressed in the adrenal cortex.

PMID- 8547174
TI  - Structure-function relationships and molecular genetics of the 3 beta
      hydroxysteroid dehydrogenase gene family.
AB  - The isoenzymes of the 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene-isomerase
      (3 beta-HSD) gene family catalyse the transformation of all 5-ene-3 beta
      hydroxysteroids into the corresponding 4-ene-3-keto-steroids and are responsible
      for the interconversion of 3 beta-hydroxy- and 3-keto-5 alpha-androstane
      steroids. The two human 3 beta-HSD genes and the three related pseudogenes are
      located on the chromosome 1p13.1 region, close to the centromeric marker D1Z5.
      The 3 beta-HSD isoenzymes prefer NAD+ to NADP+ as cofactor with the exception of
      the rat liver type III and mouse kidney type IV, which both prefer NADPH as
      cofactor for their specific 3-ketosteroid reductase activity due to the presence
      of Tyr36 in the rat type III and of Phe36 in mouse type IV enzymes instead of
      Asp36 found in other 3 beta-HSD isoenzymes. The rat types I and IV, bovine and
      guinea pig 3 beta-HSD proteins possess an intrinsic 17 beta-HSD activity specific
      to 5 alpha-androstane 17 beta-ol steroids, thus suggesting that such "secondary"
      activity is specifically responsible for controlling the bioavailability of the
      active androgen DHT. To elucidate the molecular basis of classical form of 3 beta
      HSD deficiency, the structures of the types I and II 3 beta-HSD genes in 12 male
      pseudohermaphrodite 3 beta-HSD deficient patients as well as in four female
      patients were analyzed. The 14 different point mutations characterized were all
      detected in the type II 3 beta-HSD gene, which is the gene predominantly
      expressed in the adrenals and gonads, while no mutation was detected in the type
      I 3 beta-HSD gene predominantly expressed in the placenta and peripheral tissues.
      The mutant type II 3 beta-HSD enzymes carrying mutations detected in patients
      affected by the salt-losing form exhibit no detectable activity in intact
      transfected cells, at the exception of L108W and P186L proteins, which have some
      residual activity (approximately 1%). Mutations found in nonsalt-loser patients
      have some residual activity ranging from approximately 1 to approximately 10%
      compared to the wild-type enzyme. Characterization of mutant proteins provides
      unique information on the structure-function relationships of the 3 beta-HSD
      superfamily.

PMID- 8547175
TI  - Organization of 3 beta-hydroxysteroid dehydrogenase/isomerase and cytochrome
      P450scc into a catalytically active molecular complex in bovine adrenocortical
      mitochondria.
AB  - We have previously reported the co-localization [Cherradi et al., Endocrinology
      134 (1994) 1358-1364] of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta
      HSD) and cytochrome P450scc (cyt. P450scc) in the inner membrane and in the
      intermembrane contact sites of adrenocortical mitochondria. This observation
      raises the question of a possible functional association between the two
      proteins. Isolated bovine adrenocortical mitochondria are able to convert
      cholesterol to progesterone without the need of exogenous cofactors. An
      association of 3 beta-HSD and cyt. P450scc is observed during the purification of
      3 beta-HSD from mitochondria. The behaviour of 3 beta-HSD on a column of Heparin
      Sepharose is modified by the presence of cyt. P450scc. Immunoprecipitations from
      mitochondria with either anti-cyt. P450scc or anti 3 beta-HSD antibodies result
      in a co-precipitation of the two proteins. Both proteins engaged in these
      immunocomplexes are catalytically active. The interaction was further
      demonstrated by the surface plasmon resonance method using purified components.
      An affinity demonstrated by the surface plasmon resonance method using purified
      components. An affinity constant of 0.12 microM between 3 beta-HSD and P450scc
      was obtained. These observations suggest that P450scc and 3 beta-HSD may
      associate into a molecular complex in the mitochondrial compartment and may
      constitute a functional steroidogenic unit, thus opening new possibilities in the
      regulation of the production of progesterone and its flow in the adrenocortical
      cell.

PMID- 8547176
TI  - Kinetic analysis of enzymic activities: prediction of multiple forms of 17 beta
      hydroxysteroid dehydrogenase.
AB  - An overview of the application of kinetic methods to the delineation of 17 beta
      hydroxysteroid dehydrogenase (17 beta-HSD) heterogeneity in mammalian tissues is
      presented. Early studies of 17 beta-HSD activity in animal liver and kidney
      subcellular fractions were suggestive of multiple forms of the enzyme.
      Subsequently, detailed characterization of activity in cytosol and subcellular
      membrane fractions of human placenta, with particular emphasis on inhibition
      kinetics, yielded evidence of two kinetically-differing forms of 17 beta-HSD in
      that organ. Gene cloning and transfection experiments have confirmed the identity
      of these two proteins as products of separate genes. 17 beta-HSD type 1 is a
      cytosolic enzyme highly specific for C18 steroids such as 17 beta-estradiol (E2)
      and estrone (E1). 17 beta-HSD type 2 is a membrane bound enzyme reactive with
      testosterone (T) and androstenedione (A), as well as E2 and E1. Useful parameters
      for the detection of multiple forms of 17 beta-HSD appear to be the E2/T activity
      ratio, NAD/NADP activity ratios, steroid inhibitor specificity and inhibition
      patterns over a wide range of putative inhibitor concentrations. Evaluation of
      these parameters for microsomes from samples of human breast tissue suggests the
      presence of 17 beta-HSD type 2. The 17 beta-HSD enzymology of human testis
      microsomes appears to differ from placenta. Analysis of human ovary indicates
      granulosa cells are particularly enriched in the type 1 enzyme with type 2-like
      activity in stroma/theca. Mouse ovary appears to contain forms of 17 beta-HSD
      which differ from 17 beta-HSD type 1 and type 2 in their kinetic properties.

PMID- 8547177
TI  - Role of 17 beta-hydroxysteroid dehydrogenase type 1 in endocrine and intracrine
      estradiol biosynthesis.
AB  - Enzymes with 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity catalyse
      reactions between the low-active female sex steroid, estrone, and the more potent
      estradiol, for example. 17 beta-HSD activity is essential for glandular
      (endocrine) sex hormone biosynthesis, but it is also present in several extra
      gonadal tissues. Hence, 17 beta-HSD enzymes also take part in local (intracrine)
      estradiol production in the target tissues of estrogen action. Four distinct 17
      beta-HSD isozymes have been characterized so far, and the data strongly suggests
      that different 17 beta-HSD isozymes have distinct roles in endocrine and
      intracrine metabolism of sex steroids. Current data suggest that 17 beta-HSD type
      1 is the principal isoenzyme involved in glandular estradiol production both in
      humans and rodents. During ovarian follicular development and luteinization, rat
      17 beta-HSD type 1 is regulated by gonadotropins, and the effects of
      gonadotropins are modulated by steroid hormones and paracrine growth factors.
      Human 17 beta-HSD type 1 favors the reduction reaction, thereby converting
      estrone to estradiol both in vitro and in cultured cells. Hence, the enzymatic
      properties of the enzyme are also in line with its suggested role in estradiol
      biosynthesis. Interestingly, 17 beta-HSD type 1 is also expressed in certain
      target tissues of estrogen action such as normal and malignant human breast and
      endometrium. Hence, 17 beta-HSD type 1 could be one of the factors leading to a
      relatively high tissue/plasma ratio of estradiol in breast cancer tissues of
      postmenopausal women. We conclude that 17 beta-HSD type 1 has a central role in
      regulating the circulating estradiol concentration as well as its local
      production in estrogen target cells.

PMID- 8547178
TI  - Molecular genetics of androgenic 17 beta-hydroxysteroid dehydrogenases.
AB  - 17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) type 2 catalyzes the NAD(+)
      dependent oxidation of androgens, estrogens and progestins, predominantly in the
      secretory endometrium, placenta, liver and small intestine. 17 beta-HSD type 3
      catalyzes the NADPH-dependent conversion of androstenedione to testosterone in
      the testis, and the genetic disease 17 beta-HSD deficiency is caused by mutations
      in the 17 beta-HSD3 gene.

PMID- 8547179
TI  - The tissue distribution of porcine 17 beta-estradiol dehydrogenase and its
      induction by progesterone.
AB  - Porcine 17 beta-estradiol dehydrogenase (EDH) was recently purified and cloned.
      It catalyzes the NAD(+)-dependent oxidation of estradiol to estrone 360-fold more
      efficiently than the back reaction with NADPH. The 32 kDa EDH is cut from an 80
      kDa primary translation product with a multidomain structure unknown for other
      hydroxysteroid dehydrogenases. The highest EDH activities and strongest
      immunoreactions are found in liver (hepatocytes) and kidney (proximal tubuli)
      followed by uterus (luminal and glandular epithelium), lung (bronchial
      epithelium). Progesterone treatment of ovariectomized gilts stimulates oxidative
      EDH activity in uterus, anterior pituitary, skeletal muscle (diaphragm) and
      kidney. Constitutive levels of EDH activity were seen in the adrenals, the lung
      and the liver.

PMID- 8547180
TI  - Molecular characterization of mouse 17 beta-hydroxysteroid dehydrogenase IV.
AB  - 17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) catalyze the conversion of
      estrogens and androgens at the C17 position. The 17 beta-HSD type I, II, III and
      IV share less than 25% amino acid similarity. The human and porcine 17 beta-HSD
      IV reveal a three-domain structure unknown among other dehydrogenases. The N
      terminal domains resemble the short chain alcohol dehydrogenase family while the
      central parts are related to the C-terminal parts of enzymes involved in
      peroxisomal beta-oxidation of fatty acids and the C-terminal domains are similar
      to sterol carrier protein 2. We describe the cloning of the mouse 17 beta-HSD IV
      cDNA and the expression of its mRNA. A probe derived from the human 17 beta-HSD
      IV was used to isolate a 2.5 kb mouse cDNA encoding for a protein of 735 amino
      acids showing 85 and 81% similarity with human and porcine 17 beta-HSD IV,
      respectively. The calculated molecular mass of the mouse enzyme amounts to 79,524
      Da. The mRNA for 17 beta-HSD IV is a single species of about 3 kb, present in a
      multitude of tissues and expressed at high levels in liver and kidney, and at low
      levels in brain and spleen. The cloning and molecular characterization of murine,
      human and porcine 17 beta-HSD IV adds to the complexity of steroid synthesis and
      metabolism. The multitude of enzymes acting at C17 might be necessary for a
      precise control of hormone levels.

PMID- 8547181
TI  - Intrinsic sterol- and phosphatidylcholine transfer activities of 17 beta
      hydroxysteroid dehydrogenase type IV.
AB  - Previous studies have shown that the 80 kDa 17 beta-hydroxysteroid dehydrogenase
      (17 beta-HSD) type IV comprises distinct domains, including an N-terminal region
      related to the short chain alcohol dehydrogenase multigene family and a C
      terminal part related to the lipid transfer protein sterol carrier protein 2
      (SCP2). In this study, we have investigated whether the SCP2-related part of the
      80 kDa protein leads to an intrinsic sterol and phospholipid transfer activity,
      as shown earlier for the 60 kDa SCP2-related peroxisomal 3-ketoacyl CoA thiolase
      with intrinsic sterol and phospholipid transfer activity called sterol carrier
      protein x (SCPx). Our results indicate that a fraction rich in the 80 kDa form of
      17 beta-HSD type IV exhibits high transfer activities for 7-dehydrocholesterol
      and phosphatidylcholine. In addition, a purified recombinant peptide derived from
      the SCP2-related domain of the 17 beta-HSD type IV has about 30% of the transfer
      activities for 7-dehydrocholesterol and phosphatidylcholine seen with purified
      recombinant human SCP2. We conclude that the 80 kDa type IV 17 beta-HSD
      represents a potentially multifunctional protein with intrinsic in vitro sterol
      and phospholipid transfer activity in addition to its enzymatic activity.

PMID- 8547182
TI  - Expression and regulation of aromatase and 17 beta-hydroxysteroid dehydrogenase
      type 4 in human THP 1 leukemia cells.
AB  - Estradiol is active in proliferation and differentiation of sex-related tissues
      like ovary and breast. Glandular steroid metabolism was for a long time believed
      to dominate the estrogenic milieu around any cell of the organism. Recent reports
      verified the expression of estrogen receptors in "non-target" tissues as well as
      the extraglandular expression of steroid metabolizing enzymes. Extraglandular
      steroid metabolism proved to be important in the brain, skin and in stromal cells
      of hormone responsive tumors. Aromatase converts testosterone into estradiol and
      androstenedione into estrone, thereby activating estrogen precursors. The group
      of 17 beta-hydroxysteroid dehydrogenases catalyzes the oxidation and/or reduction
      of the forementioned compounds, e.g. estradiol/estrone, thereby either activating
      or inactivating estradiol. Aromatase is expressed and regulated in the human THP
      1 myeloid leukemia cell line after vitamin D/GMCSF-propagated differentiation.
      Aromatase expression is stimulated by dexamethasone, phorbolesters and
      granulocyte/macrophage stimulating factor (GMCSF). Exons I.2 and I.4 are
      expressed in PMA-stimulated cells only, exon I.3 in both PMA- and dexamethasone
      stimulated cells. Vitamin D-differentiated THP 1 cells produce a net excess of
      estradiol in culture supernatants, if testosterone is given as aromatase
      substrate. In contrast, the 17 beta-hydroxysteroid dehydrogenase type 4 (17 beta
      HSD 4) is abundantly expressed in unstimulated THP 1 cells and is further
      stimulated by glucocorticoids (2-fold). The expression is unchanged after vitamin
      D/GMCSF-propagated differentiation. 17 beta-HSD 4 expression is not altered by
      phorbolester treatment in undifferentiated cells but is abolished after vitamin D
      propagated differentiation along with downregulation of beta-actin. Protein
      kinase C activation therefore appears to dissociate the expression of aromatase
      and 17 beta-HSD 4 in this differentiation stage along the monocyte/phagocyte
      pathway of THP 1 myeloid cells. The expression of steroid metabolizing enzymes in
      myeloid cells is able to create a microenvironment which is uncoupled from
      dominating systemic estrogens. These findings may be relevant in the autocrine,
      paracrine or iuxtacrine cellular crosstalk of myeloid cells in their respective
      states of terminal differentiation, e.g. in bone metabolism and inflammation.

PMID- 8547183
TI  - The role and proposed mechanism by which oestradiol 17 beta-hydroxysteroid
      dehydrogenase regulates breast tumour oestrogen concentrations.
AB  - Synthesis of the biologically active oestrogen, oestradiol, within breast tumours
      makes an important contribution to the high concentrations of oestrogens which
      are present in malignant breast tissues. In breast tumours, oestrone is
      preferentially converted to oestradiol by the Type I oestradiol 17 beta
      hydroxysteroid dehydrogenase (E2DH). Several growth factors, such as insulin-like
      growth factor Type I, and cytokines, such as Tumour Necrosis Factor alpha (TNF
      alpha), have been shown to stimulate E2DH activity in MCF-7 breast cancer cells.
      As little is known about the regulation of Type I E2DH expression and activity in
      other breast cancer cell lines, the expression and activity of this enzyme was
      examined in other oestrogen receptor positive and also oestrogen receptor
      negative breast cancer cell lines. As it is possible that E2DH activity may be
      limited by co-factor availability, the effects of exogenous co-factors on enzyme
      activity in these cell lines was also investigated. For T47D and BT20 breast
      cancer cells, the addition of exogenous co-factors was found to enhance enzyme
      activity. TNF alpha, in addition to stimulating E2DH activity in MCF-7 cells,
      also increased activity in T47D and MDA-MB-231 cells, although to a lesser extent
      than in MCF-7 cells. An investigation of signalling pathways involved in the
      regulation of E2DH activity revealed that stimulation of both the protein kinase
      C (PKC) and PKA pathways may be involved in regulation of E2DH activity. As
      several growth factors and cytokines have now been found to be involved in
      regulating E2DH activity, the role that macrophages and lymphocytes have in
      supplying these factors and the mechanism by which these factors may stimulate
      tumour growth, is also reviewed.

PMID- 8547184
TI  - 17 beta-Hydroxysteroid dehydrogenase activity in endometrial cancer cells:
      different metabolic pathways of estradiol in hormone-responsive and non
      responsive intact cells.
AB  - In this paper we report that two human long-term endometrial cancer cell lines,
      Ishikawa and HEC-1A, exhibit quite different abilities in metabolizing estrogens.
      As a matter of fact, incubation of Ishikawa cells with close-to-physiological
      concentrations of estradiol (E2) as precursor resulted in: (1) elevated formation
      (up to 90%) of E2-sulphate (E2-S), using lower precursor concentrations; (2) very
      limited conversion to estrone (E1) (< 10% at 24 h incubation), as either free or
      sulphate; and (3) low but consistent production of other estrogen derivatives,
      such as 2-hydroxy-estrogens and estriol. Conversely, scant amounts (if any) of E2
      S were found in HEC-1A cells, while no detectable formation of other estrogen
      metabolites could be observed after 24 h. On the other hand, E1 production was
      significantly greater (nearly 60% at 24 h) than in Ishikawa cells, a large
      proportion of E1 (over 50% of the total) being formed after only 6 h incubation
      using time-course experiments. The hypothesis that E2 metabolism could be minor
      in Ishikawa cells as a consequence of the high rate of E2-S formation encountered
      is contradicted by the evidence that conversion to E1 also remains limited in the
      presence of much lower E2-S amounts, seen using higher molar concentrations of
      precursor. Overall, we observe that 17 beta-hydroxysteroid dehydrogenase (17 beta
      HSD) activity diverges significantly in intact Ishikawa and HEC-1A endometrial
      cancer cells. This difference could not merely be accounted for by the diverse
      amounts of substrate (E2) available to the cells, nor may it be imputed to
      different levels of endogenous estrogens. It should rather be sought in different
      mechanisms controlling 17 beta-HSD activity or, alternatively, in the presence of
      distinct isoenzymes in the two different cell types.

PMID- 8547185
TI  - Characteristics of human types 1, 2 and 3 17 beta-hydroxysteroid dehydrogenase
      activities: oxidation/reduction and inhibition.
AB  - Following transfection of types 1, 2 and 3 17 beta-hydroxysteroid dehydrogenase
      (17 beta-HSD) cDNAs into transformed embryonal kidney (293) cells, we have
      characterized the selective directional and inhibitory characteristics of these
      activities. While homogenates of transfected cells could catalyze interconversion
      of the substrate and product, in agreement with the general belief on the
      activity of these enzymes, the same activities measured in intact cells, in order
      to better reflect the physiological conditions, showed an unidirectional
      reaction. Types 1 and 3 17 beta-HSD catalyzed the reduction of estrone to
      estradiol and 4-androstenedione to testosterone, respectively, while type 2 17
      beta-HSD catalyzed the oxidative transformation of both testosterone and 17 beta
      estradiol to 4-androstenedione and estrone, respectively. In addition, types 1, 2
      and 3 17 beta-HSD activities showed different pH optima. While types 1 and 3
      showed pH optimum values centered at around 5 and 6, respectively, type 2 17 beta
      HSD activity, which preferentially, catalyzes the oxidation reaction, has higher
      activity at an alkaline pH (8-10). Differences in the optimum incubation
      temperatures were also observed: type 1 17 beta-HSD shows a relatively high
      temperature tolerance (55 degrees C). In contrast, type 2 and 3 functioned best
      at 37 degrees C. Types 1, 2 and 3 17 beta-HSD activities could be also
      differentiated by their sensitivity toward various specific inhibitors: type 1
      was potently inhibited by an estradiol derivative containing a bromo/or
      iodopropyl group at position 16 alpha. On the other hand a derivative of estrone
      containing a spiro-gamma-lactone at position 17 showed a potent inhibitory effect
      on type 2 17 beta-HSD, whereas type 3 was strongly inhibited by 1,4-androstadiene
      1,6,17- trione.

PMID- 8547186
TI  - Structures important in mammalian 11 beta- and 17 beta-hydroxysteroid
      dehydrogenases.
AB  - We have used the X-ray crystallographic structures of rat and human
      dihydropteridine reductase and Streptomyces hydrogenans 20 beta-hydroxysteroid
      dehydrogenase to model parts of the 3-dimensional structure of human 11 beta- and
      17 beta-hydroxysteroid dehydrogenases. We use this information along with
      previous results from studies of Drosophila alcohol dehydrogenase mutants to
      analyze the structures in binding sites for NAD(H) and NADP(H) in 11 beta
      hydroxysteroid dehydrogenase-types 1 and 2. We also examine the structure of an
      alpha-helix at catalytic site of 17 beta-hydroxysteroid dehydrogenase-types 1, 2,
      3, and 4. This alpha-helix contains a highly conserved tyrosine and lysine.
      Adjacent to the carboxyl side of this lysine is a site proposed to be important
      in subunit association. We find that 11 beta- and 17 beta-hydroxysteroid
      dehydrogenases-type 1 have the same residues at the "anchor site" and conserve
      other stabilizing features, despite only 20% sequence identity between their
      entire sequences. Similar conservation of stabilizing structures is found in the
      11 beta- and 17 beta-hydroxysteroid dehydrogenases-type 2. We suggest that
      interactions of the dimerization surface of alpha-helix F with proteins or
      membranes may be important in regulating activity of hydroxysteroid
      dehydrogenases.

PMID- 8547187
TI  - The roles of microfilaments and intermediate filaments in the regulation of
      steroid synthesis.
AB  - Much of the cholesterol used in steroid synthesis is stored in lipid droplets in
      the cytoplasm of steroid-forming cells. The cholesterol ester in these droplets
      is transported to the inner mitochondrial membrane where it enters the pathway to
      steroid hormones as free cholesterol--the substrate for the first enzyme, namely
      P450scc. It has been shown that this transport process governs the rate of
      steroid synthesis and is specifically stimulated by ACTH and its second
      messenger. The stimulating influence of ACTH on cholesterol transport is
      inhibited by cytochalasins, by monospecific anti-actin and by DNase I
      demonstrating that the steroidogenic cell must possess a pool of monomeric actin
      available for polymerization to F actin if it is to respond to ACTH and cyclic
      AMP. It has been shown that the two structures involved in cholesterol transport
      (droplets and mitochondria) are both bound to vimentin intermediate filaments in
      adrenal and Leydig cells. In addition these filaments are closely associated with
      the circumferential actomyosin ring in which they are crosslinked by actin
      microfilaments. In permeabilized adrenal cells Ca2+/calmodulin phosphorylates
      vimentin and this change is known to disrupt intermediate filaments and to cause
      contraction of actomyosin by phosphorylating myosin light chain kinase.
      Ca2+/calmodulin stimulated cholesterol transport and steroid synthesis and causes
      rounding of the responding cells by contraction of the actomyosin, if ATP is also
      added at the same time. Other agents that disrupt intermediate filaments include
      anti-vimentin plus ATP in permeabilized cells which also results in rounding of
      the cell. Acrylamide exerts a similar effect in intact adrenal cells and in
      addition causes rounding of the cells and increase in steroid synthesis without
      increase in cyclic AMP. It is also known that if adrenal cells are grown on
      surfaces treated with poly(HEMA), the cells grow in rounded form and steroid
      synthesis is increased in proportion to the degree of rounding (r = 0.92). This
      response does not involve increase in cellular levels of cyclic AMP. It is
      proposed that in vivo where the cell is always round and cannot show more than
      strictly limited change in shape, ACTH activates Ca2+/calmodulin possibly by
      redistributing cellular Ca2+. Ca2+/calmodulin in turn promotes phosphorylation of
      vimentin and myosin light chain. The first of these phosphorylations shortens
      intermediate filaments and the second promotes contraction of the actomyosin ring
      with internal shortening and approximation of lipid droplets and mitochondria.
      Details of the earlier events (activation of Ca2+/calmodulin) and later changes
      (transfer of cholesterol to the inner membrane) remain to be elucidated. It is
      clear however that the action of ACTH requires increase in cellular cyclic AMP.
      These experimental responses bypass this step in the response to ACTH.

PMID- 8547188
TI  - Mitochondrial specificity of the early steps in steroidogenesis.
AB  - Studies in human beings, animals, and cell systems show that the rate-limiting
      step in steroidogenesis is the conversion of cholesterol to pregnenolone. In the
      adrenals and gonads, this step is subject to both acute and chronic regulation.
      Chronic regulation is primarily, but not exclusively at the level of gene
      transcription, leading to the production of more steroidogenic machinery and thus
      increasing the cellular capacity for steroidogenesis. Chronic regulation can be
      inhibited by inhibiting protein synthesis with cycloheximide, but this response
      varies among various cell types and species. Although the P450scc enzyme system
      that converts cholesterol to pregnenolone is inherently very slow, the principal
      site of acute regulation is at the delivery of free cholesterol to mitochondria,
      rather than at the delivery of reducing equivalents to P450scc. Even when the
      Vmax of the P450scc system is increased 6-fold by genetic engineering, delivery
      of cholesterol to the enzyme remains rate-limiting. Targeting of a genetically
      engineered fusion of the P450scc system to either mitochondria or to the
      endoplasmic reticulum of non-steroidogenic cells demonstrates that the
      mitochondrial environment is absolutely required for the conversion of
      cholesterol to pregnenolone, and that this absolute requirement is not based on
      either the nature of the available electron donors for P450scc or the
      availability of substrate. Various factors have been proposed as the essential
      mediator for the transport of cholesterol into mitochondria to initiate
      steroidogenesis. A recently identified protein termed Steroidogenic Acute
      Regulatory protein (StAR) has the necessary properties of enhancing
      steroidogenesis, rapid cAMP inducibility and rapid cycloheximide sensitivity that
      characterize the long-sought acute regulator of steroidogenesis. StAR is
      expressed in steroidogenic tissues exhibiting an acute response but not in
      steroidogenesis. StAR is expressed in steroidogenic tissues exhibiting an acute
      response but not in steroidogenic tissues (placenta, brain) that do not exhibit
      this response. Mutations in StAR are now shown to cause Congenital Lipoid Adrenal
      Hyperplasia, the last unsolved form of CAH. The actions of StAR can be
      circumvented by the use of hydroxycholesterols that can freely diffuse into
      mitochondria, proving that StAR functions as an acute regulator of cholesterol
      access to mitochondria.

PMID- 8547189
TI  - The subcellular localization of 17 beta-hydroxysteroid dehydrogenase type 4 and
      its interaction with actin.
AB  - The porcine 17 beta-hydroxysteroid dehydrogenase type 4 is the key enzyme for the
      inactivation of estradiol. Its localization in peroxisomes was proven by
      immunogold electron microscopy. Interactions of the 17 beta-hydroxysteroid
      dehydrogenase with cytoskeletal proteins might be mandatory for a topical
      assignment of enzymatic activity to defined subcellular compartments.

PMID- 8547190
TI  - The natural history of operable breast cancer after primary treatment.
AB  - This paper aimed at reviewing information on the natural history of operable
      breast carcinoma after primary treatment. Breast carcinoma does not appear as a
      single disease entity, but as a wide variety of clinical manifestations. Primary
      loco-regional treatment should have a curative aim. However, the probability of
      early or late relapse increases according to a series of prognostic factors. The
      axillary node status remains the main prognostic indicator but especially in node
      negative patients, an increasing number of additional morphologic and biological
      prognostic factors can classify patients according to a low, good or high risk
      categories. The natural history of the disease is influenced by loco-regional
      treatment as far as loco-regional control is concerned. The risk of relapse after
      loco-regional treatment alone differs during the first three years according to
      nodal status and it then tends to decrease and become more homogeneous. Adjuvant
      systemic therapies can decrease the probability of relapse, mainly in loco
      regional but rarely in distant sites, thus limiting the absolute advantage. In
      any case, most women after primary treatment are not cured and are still carriers
      of occult disease. A timely diagnosis of first relapse after primary treatment is
      the direct aim of follow-up. An improvement in survival is only an indirect aim
      of the follow-up, and depends, if at all, on an anticipated diagnosis of
      recurrence, on the disease site in which this anticipated diagnosis is feasible
      and on application of different therapeutic strategies according to disease
      extension and to disease site. Follow-up could be tailored according to time
      after primary treatment (with more frequent examinations during the first three
      years than thereafter) and according to prognostic factors, mainly the axillary
      nodal status. Follow-up should not be considered as conceptually independent
      either from primary treatment or from treatment after recurrence. At time of
      first relapse, a new prognostic evaluation can be based on sites of disease
      recurrence, ER status at time of diagnosis and the time interval from primary
      treatment to relapse. Different therapeutic approaches could be planned according
      to survival expectation, including experimental treatments for patients having a
      dire prognosis.

PMID- 8547191
TI  - Detection of breast cancer local recurrences.
AB  - BACKGROUND: Early detection of locoregional recurrences of breast cancer is
      possible with a variety of diagnostic methods. A combination of palpation,
      sonography and aspiration cytology is probably as accurate and certainly simpler,
      faster and cheaper compared to other more complicated and costly tests
      (computerized tomography, magnetic resonance imaging, lymphoscintigraphy).
      Retrospective studies have estimated that periodic observation may anticipate the
      detection of local symptomatic recurrences of about 3 months time with respect to
      their symptomatic onset. After correcting for lead time, this anticipated
      diagnosis has a moderate to null effect on prognosis (survival from primary
      treatment) in retrospective studies. According to their natural history, most
      local recurrences are just a local presentation of diffuse metastatization and,
      except for a few subgroups (isolated recurrent nodules in the mastectomy scar,
      isolated axillary nodes), prolonged disease-free survival suggests the absence of
      associated progressing systemic disease. CONCLUSIONS: Periodic control aimed at
      the early detection of these local recurrences might be recommended, although the
      prognostic impact (if any) of such a policy is probably limited, and extremely
      large controlled studies would be necessary to demonstrate impact at a
      significant level.

PMID- 8547193
TI  - Patient participation in medical consensus conferences.

PMID- 8547192
TI  - Radiologic procedures for the diagnosis of distant recurrences of breast cancer.
AB  - BACKGROUND: The problems related to a correct, effective and possibly inexpensive
      radiological follow-up of patients with breast cancer are presented. METHOD:
      Different viewpoints are reported and analyzed and a diagnostic protocol which
      includes the vast majority of clinical presentations and situations is suggested.

PMID- 8547194
TI  - Tumor markers in breast cancer follow-up: a potentially useful parameter still
      awaiting definitive assessment. Forza Operativa Nazionale sul Carcinoma Mammario
      (FONCaM).
AB  - BACKGROUND: Although tumor markers are frequently used in the follow-up of
      patients with breast cancer, two points are still being debated: 1) their
      cost/effectiveness has been neither demonstrated nor disproved; 2) the
      reliability of the currently used dichotomous division into a positive/negative
      cut-off should be definitely validated. Dynamic criteria of interpretation based
      on serial serum samples would probably be more effective for early detection of
      relapse. PATIENTS AND METHODS: The aim of the present study was to compare the
      dichotomous cut-off based decision criteria to a dynamic serial sample based
      assessment of tumor markers. Since 1989, 794 patients have been followed in 11
      institutions. CEA and CA15.3 were measured once a month for three months before
      every clinical examination. The present paper concerns the evaluation variability
      in 405 patients without evidence of disease in the first three institutions
      joining the study. RESULTS: In patients without evidence of disease, the
      coefficient of variation of all samples for every patient showed a median value
      of 19 for CEA and 21 for CA15.3. Variability was negatively associated with the
      antigen level and was most likely due to the analytical component. This was also
      confirmed by the significant difference in variability among the three
      institutions evaluated. The median value of the critical difference was 53% for
      CEA and 57% for CA15.3. CONCLUSIONS: 1) Individually tailored dynamic decision
      criteria are applicable in about 50% of the cases. 2) The problem of improving
      the precision of tumor marker assays in the low dose range must be urgently
      addressed to the manufacturers of tumor markers by the scientific community in
      order to apply individually tailored decision criteria for patients in whom the
      serum level of biological markers is low.

PMID- 8547195
TI  - The efficacy of intensive follow-up testing in breast cancer cases.
AB  - BACKGROUND: A preliminary inquiry into the follow-up practices of Italian breast
      cancer centers revealed a considerable diversity of policy. It is clear that
      accurate follow-up examinations supply important information about the
      development of metastases, but there is no clinical proof that they extend
      survival time. It is possible that the effects of early diagnosis are only
      negative, extending the period over which the patient is aware of her illness and
      leading to over-diagnosis, overtreatment and increased health-care costs.
      PATIENTS AND METHODS: In a study involving the national oncological centers,
      patients were randomized into two groups: an intensive follow-up group (6 monthly
      chest X-rays and bone scans) and a control group (clinical examination only).
      RESULTS: An excess of isolated bone and intrathoracic metastases were observed in
      the intensive follow-up group. The survival curves showed no difference between
      the two groups. CONCLUSIONS: Six monthly X-rays and bone scans provide occasion
      for early diagnosis of intrathoracic and bone metastases without, however,
      influencing overall 5-year survival. Recourse to diagnostic tests only in the
      presence of symptoms appears to be the most appropriate follow-up procedure.
      However, other studies considering long term effects of early diagnosis and the
      effects of considering long term effects of early diagnosis and the effects of
      new diagnostic tests and/or treatment modalities are clearly needed.

PMID- 8547196
TI  - The GIVIO trial on the impact of follow-up care on survival and quality of life
      in breast cancer patients. Interdisciplinary Group for Cancer Care Evaluation.
AB  - BACKGROUND: The aim of the study was to prospectively assess the impact on
      survival and health-related quality of life of two different follow-up policies
      in patients with early breast cancer. PATIENTS AND METHODS: A consecutive sample
      of 1320 women with stage I, II and III unilateral primary breast cancer, aged up
      to 70 years, were randomly assigned to an intensive surveillance which included
      physician visits, and performance of bone scans, liver sonograms, chest X-rays
      and laboratory tests at predefined intervals (655 patients) or to a control
      regimen (665 patients) in which patients were seen by their doctors at the same
      frequency but only clinically motivated tests were performed. Both groups
      received a yearly mammogram aimed at detecting contralateral breast cancer. The
      primary end-points were overall survival and health-related quality of life.
      RESULTS: Compliance to the two follow-up policies was over 80%. After a median
      follow-up of 71 months, no difference was apparent in overall survival with 132
      (20%) and 122 (18%) deaths in the intensive and control group, respectively. No
      significant differences were apparent in time to detection of recurrence between
      the two groups. Measurements of health-related quality of life (i.e., overall
      health and quality of life perception, emotional well-being, body image, social
      functioning, symptoms and satisfaction with care) at 6, 12, 24 and 60 months of
      follow-up did not differ according to regimen. CONCLUSIONS: Results of this trial
      support the view that a policy of frequent laboratory and X-ray tests and
      procedures after primary treatment for breast cancer does not improve survival
      nor influence health-related quality of life. Routine use of these tests should
      be discouraged.

PMID- 8547197
TI  - Evaluating primary care follow-up of breast cancer: methods and preliminary
      results of three studies.
AB  - OBJECTIVE: To evaluate a primary care centred system of routine follow-up of
      women with breast cancer in remission. DESIGN, PATIENTS AND OUTCOME MEASURES:
      Three related studies are reported: 1) A randomized controlled trial (RCT)
      involving 296 women with breast cancer in remission (stage I, II, or III) all
      receiving routine follow-up at two district general hospitals in England. Women
      in the control group received follow-up in hospital clinics according to the
      usual practice. Women in the experimental group received follow-up from their own
      general practitioners (GP), and were referred back to hospital clinics if any
      breast cancer related problems developed. The main outcome of the trial was
      'diagnostic delay': the time from the first presentation of signs or symptoms
      suggestive of recurrence to the time that recurrence was diagnosed. 2) A
      prospective descriptive study of a cohort of 141 women who were eligible for the
      trial, but who declined to participate. 3) A national survey of 376 specialists
      in breast cancer, and a survey of 226 general practitioners of the patients
      eligible for the RCT described above, to determine their views on follow-up of
      breast cancer in remission. RESULTS: 1) The randomized trial to evaluate primary
      care follow-up of breast cancer in remission has been successfully conducted and
      final results are pending. 2) Patients who were eligible but declined to
      participate in the trial were significantly older than participants (mean age
      64.3 years compared with 60.7 years; difference 3.6 years; 95% confidence
      interval 0.53; 6.59). The two groups were similar in clinical characteristics and
      quality of life. 3) The majority of specialists and GPs preferred a system of
      routine follow-up which was primarily provided by their own professional group.
      CONCLUSIONS: A general practice centred system of routine follow-up of women with
      breast cancer in remission is acceptable to both patients and general
      practitioners. Final results of a randomized trial evaluating quality of care and
      quality of life outcome measures are pending.

PMID- 8547198
TI  - A shared effort toward better quality of care. The Consensus Conference on Breast
      Cancer Follow-up. Consensus Conference Organizing Committee.
AB  - BACKGROUND: Even though several radiological and laboratory tests are currently
      used in clinical practice for breast cancer surveillance, the benefits of early
      detection of distant metastases have never been established. Two recently
      published randomized clinical trials assessing the effectiveness of an intensive
      follow-up strategy (with periodic clinical examination, mammography, bone scan,
      liver echography, chest-X-ray and laboratory tests) over a minimalist one
      (including only periodic clinical examination and mammography) failed to show a
      significant advantage for the more intensive policy. Intensive follow-up,
      however, is quite common in clinical practice. AIM OF THE CONSENSUS CONFERENCE:
      To contribute to the definition of the state of the art in this field and develop
      recommendations for follow-up in clinical practice. CONDUCT OF THE CONSENSUS
      CONFERENCE: A Jury, including representatives from all the relevant stakeholders,
      (professional societies, patients and consumer associations, epidemiologists,
      health economists and administrators) was convened to critically appraise and
      interpret available scientific evidence and the information provided by three
      specific working groups which had the task of examining the clinical, economic
      and psyco-social aspects of breast cancer follow-up, respectively. CONCLUSIONS:
      This conference was planned to make explicit and properly represent the
      viewpoints of all the stakeholders. Furthermore, special efforts were devoted to
      the development of final recommendations in sufficient detail so as to provide a
      significant aid for decision-making in clinical practice. It is argued that the
      Consensus Conference model, designed to elicit and represent the interpretation
      of scientific evidence by all the stakeholders, would be useful for the
      development of clinical policies more in line with societal values.

PMID- 8547199
TI  - A survey in Puglia: the attitudes and opinions of specialists, general physicians
      and patients on follow-up practice. G.S.Bio.Ca.M.
AB  - BACKGROUND: The follow-up for breast cancer patients is a well established
      routine practice requiring the organization and coordination of many professional
      figures and a large expenditure of national health funds. To study the problems
      in practical clinical management of such a complicated health program in a
      typical population, a questionnaire survey of the opinions and attitudes of
      specialists, general practitioners and patients directly involved in clinical
      follow-up was performed in the Puglia region of Southern Italy. MATERIALS AND
      METHODS: A representative sample of specialists (n = 285), general practitioners
      (n = 263) and patients (n = 284) involved in the management of follow-up practice
      for breast cancer in Puglia received different questionnaires to ascertain their
      behaviour, attitudes, opinions, perception of the disease and the organizational
      requirements for treatment. A total of 57.4% of questionnaires were returned.
      RESULTS AND DISCUSSION: The most important results were: (a) about one-third of
      cases complained of difficulties in follow-up management due to the lack of
      cooperation and integration of follow-up procedures among specialists; (b) the
      general practitioners preferred to have a more active role in follow-up; (c) the
      patients reported that being managed by more than one physician or living far
      from follow-up facilities resulted in an inferior quality of life.

PMID- 8547200
TI  - Appropriateness of the use of clinical and radiologic examinations and laboratory
      tests in the follow-up of surgically-treated breast cancer patients. Results of
      the Working Group on the Clinical Aspects of Follow-up.
AB  - BACKGROUND: The aim of this working group was to assess the appropriateness of
      use of radiologic examinations, laboratory tests and periodic check-ups for
      surgically-treated, disease-free breast cancer patients. MATERIALS AND METHODS: A
      total of 252 clinical scenarios (36 for each of the 8 exams considered: clinical
      examination, mammography, chest roentgenography, hematochemical tests, markers,
      bone scan, liver echography/abdominal CT scan), each representing a specific
      surgically treated and disease-free breast cancer patient, were rated by the
      members of the panel. A 3 point scale was utilized as to whether the test in
      question was judged inappropriate (1), questionable (2), or appropriate (3) (in
      the latter case the panel member was also asked for the advised frequency of the
      exam expressed in months). RESULTS: After two assessment sessions, consensus
      among members of the panel was reached on 216 of the 252 scenarios; disagreement
      remained on only 36 clinical scenarios. CONCLUSIONS: The panel agreed that only
      clinical examinations and mammographies should be recommended for routine
      clinical follow-up of surgically-treated breast cancer patients. Given the
      current available therapeutic options, these would assure adequate medical care
      and psychological aid.

PMID- 8547201
TI  - Economic evaluation of diagnostic follow-up after primary treatment for breast
      cancer. Results of the Working Group on Economic-Organizational Aspects of Follow
      up.
AB  - BACKGROUND: This study examined costs associated with different 5-year follow-up
      regimens (intensive vs. minimum) in patients after primary breast cancer
      treatment. METHODS: Since the results of two randomised controlled trials showed
      a similar 5-year survival for asymptomatic patients followed with frequent
      diagnostic tests and patients followed with only routine clinical controls, the
      economic savings resulting from the systematic adoption of a minimum surveillance
      regimen were estimated for Italy. RESULTS: When considering only direct health
      care costs (i.e., excluding time and travel costs) and adopting a minimalist
      policy, the average per patient savings (5% yearly compound rate) were calculated
      at 3.7 million Italian lire for paying patients, 2.5 million Italian lire for
      patient reimbursement from private voluntary/integrative health insurance funds,
      and to range from 1.2 to 2.1 million Italian lire for payment to the National
      Health Service (NHS). Total follow-up savings for the patient cohort which had
      breast surgery in the last 5 years were estimated to range from 29 to 51 billion
      Italian lire for the NHS, 92 billion Italian lire for paying patients and 62
      billion Italian lire for the health insurance funds. CONCLUSIONS: Alternative use
      of these savings were discussed with reference to breast cancer screening
      programs.

PMID- 8547202
TI  - The patient's point of view. Results of the Working Group on Socio-Psychological
      Implications of Follow-up.
AB  - AIM OF THE STUDY GROUP FOR PSYCHO-SOCIAL IMPLICATIONS OF FOLLOW-UP: For the first
      time in Italy, patients and members of breast-cancer patients' associations have
      been offered the opportunity to participate in the production of recommendations
      for the framework of a national Consensus Conference on the follow-up of breast
      cancer. ORGANIZATION AND METHODS OF THE WORKING GROUPS: Three different working
      groups were assembled. The first performed an 'epidemiological analysis',
      starting with available data from surveys carried out in Italy. The second
      performed a qualitative assessment of personal response to the follow-up
      experience. Finally, the third group organized a focus group of patients treated
      in the Apulia region, coordinated by a surgeon, a radiotherapist and a
      psychologist. CONCLUSIONS: The final document presented to the Jury of the
      Conference focused on five aspects particularly relevant to the patients: 1. the
      need of a regular clinical examination as a key point of follow-up; 2. the
      importance of being assured of continuity of care delivered by a
      multidisciplinary team; 3. the importance of full information sharing between
      patient and physician on diagnosis and follow-up; 4. the need for explicit
      guidelines to assure that patients receive good quality care and to minimize
      unjustified variations; 5. the importance of breast cancer patients' associations
      was confirmed by all participants.

PMID- 8547203
TI  - Consensus Conference on 'Follow-up of Breast Cancer Patients'.

PMID- 8547204
TI  - R56865 is antifibrillatory in reperfused ischemic guinea-pig hearts, even when
      given only during reperfusion.
AB  - R56865 was previously characterized as an inhibitor of Na and Ca overload that
      has beneficial effects during ischemia and reperfusion. An isolated guinea-pig
      heart preparation was subjected to 60 minutes of ischemia and 60 minutes of
      reperfusion. R56865 was given before ischemia and with the onset of reperfusion,
      applying different dosing schedules, including an initial loading dose. R56865
      below 0.1 mumol/l had no cardiodepressant effects in normoxic hearts and at 0.1
      mumol/l reduced left ventricular pressure marginally. The onset of ischemic
      contracture was delayed only at this concentration. R56865 given before ischemia
      potently inhibits delayed sustained fibrillation occurring during reperfusion in
      the concentration range between 0.01 mumol/l and 0.1 mumol/l. Analysis of
      cellular Na+, K+, and Ca2+ concentrations revealed that R56865 substantially
      improves the ionic homeostasis of myocardial cells. Most importantly, the
      compound also reduced the incidence of delayed sustained fibrillation when given
      at the onset of reperfusion. R56865 was most effective when fast equilibration of
      drug with tissue was achieved by giving an initial loading dose. In particular,
      the cellular Na+ and Ca2+ contents were improved using this dosing scheme. The
      results are compatible with the classification of R56865 as an inhibitor of Na+
      and Ca2+ overload.

PMID- 8547205
TI  - Electropharmacology of the bradycardic agents alinidine and zatebradine (UL-FS
      49) in a conscious canine ventricular arrhythmia model of permanent coronary
      artery occlusion.
AB  - Myocardial infarction was produced in 27 anesthetized dogs by ligating the left
      anterior descending (LAD) coronary artery proximal to the septal branch. Nineteen
      of these animals survived the operation and were studied by programmed
      stimulation in a random sequence between the third and seventh days after the
      infarct. Complete electrophysiologic testing was implemented in each animal prior
      to and after single doses of either alinidine (1 mg/kg IV) or zatebradine (0.5
      mg/kg IV). Alinidine prevented reinduction of sustained ventricular tachycardia
      (SVT) in only 2 of 9 dogs and zatebradine in 1 of 8 dogs. The SVT cycle length
      was not significantly changed in all cases in which it was still inducible
      despite drug administration (p > 0.05). Alinidine lengthened the effective
      refractory period (ERP) in the AV node (p < 0.01), whereas zatebradine did not
      induce a statistically significant prolongation. Conversely, zatebradine
      increased the left ventricular ERP, while alinidine left it almost unchanged. The
      rate-corrected QT interval (QTc) did not significantly differ from control values
      after the administration of either agents. Also, the duration and the ERP of
      infarctzone potentials, defined as late potentials, remained unaltered. The
      results indicate that the bradycardic agents alinidine and zatebradine do not
      exert antiarrhythmic efficacy against SVT induced during subacute myocardial
      infarction in conscious dogs. None of these drugs substantially changed
      ventricular electrophysiology or showed a drug-specific proarrhythmic effect.

PMID- 8547206
TI  - Effect of magnesium on ischemic and reperfusion arrhythmias in a canine model
      with diminished collateral blood flow.
AB  - To assess the effects of elevated serum magnesium on ischemic and reperfusion
      arrhythmias, the left anterior descending coronary artery was cannulated and
      perfused by a shunt from a carotid artery in 20 open-chest anesthetized dogs.
      Ischemia was caused for 30 minutes by shunt occlusion and retrograde diversion of
      collateral blood flow. Dogs (10/group) were treated prior to occlusion with
      either saline or MgSO4 (100 mg/kg IV). Plasma magnesium rose from 0.72 +/- 0.05
      mM to 3.89 +/- 0.29 mM before occlusion (p < 0.01) and fell to 3.28 +/- 0.21 mM
      just before reperfusion (p < 0.01). Compared to saline, magnesium significantly
      slowed heart rate (113 +/- 4 beats/min vs. 124 +/- 3 beats/min, p < 0.05),
      lowered arterial blood pressure (90 +/- 2 mmHg vs. 111 +/- 4 mmHg, p < 0.05), and
      reduced myocardial blood flow to the ischemic zone before the occlusion (59 +/- 7
      ml/min/100 g vs. 83 +/- 5 ml/min/100 g, p < 0.01). The incidence of ventricular
      tachycardia during occlusion was 80% in the saline group and 70% in the magnesium
      group (p = 1.0). The time required for a monophasic complex to develop in an
      electrogram over the ischemic zone was 4.5 +/- 0.24 minutes in the saline group
      and was not altered by magnesium (4.6 +/- 0.18 minutes). The incidence of
      reperfusion-induced ventricular fibrillation was 100% in both groups. The results
      suggest that acute infusion of magnesium offers little protection against
      ventricular tachyarrhythmias evoked by occlusion or reperfusion in a canine model
      of myocardial ischemia with diminished collateral blood flow.

PMID- 8547207
TI  - "Normal" response of the QT interval and QT dispersion following intravenous
      injection of the sodium channel blocker disopyramide: methodological aspects.
AB  - Measurement of the QT dispersion (the maximal interlead difference) on the
      surface electrocardiogram has been suggested for assessing the risk for
      ventricular arrhythmias and for examining drug effects and their proarrhythmic
      potential. The acute response of QT dispersion was assessed in 10 healthy
      subjects receiving disopyramide, which is known to delay repolarization and to
      prolong global measures thereof. The QRS, JT, and QT intervals and their
      dispersion were assessed at spontaneous rhythm and at atrial pacing at baseline
      and after an intravenous injection of disopyramide 2 mg/kg over 5 minutes. The
      short-term (within 30 minutes) and long-term (> or = 2 weeks) variabilities of
      the QT interval and the QT dispersion, expressed as the coefficient of variation,
      were also analyzed. At spontaneous rhythm the group average QT interval was
      between 369 and 375 msec, and the QT dispersion was between 33 and 37 msec; both
      were relatively stable over time. All subjects responded homogeneously to
      disopyramide with a significant QT prolongation (p < 0.001), but no consistent
      response of the QT dispersion was observed. This discrepancy reflects the
      significant difference in time-dependent variability with a coefficient of
      variation of spontaneous, paced, and heart rate-corrected QT dispersion between
      25% and 42%, 8-42 times greater than the corresponding values of 1-4% for the QT
      intervals. The individual response of the QT dispersion to drug challenge should
      therefore be interpreted with caution. Furthermore and as a consequence, QT
      dispersion is less sensitive for assessing drug effects on ventricular
      depolarization and repolarization than the QT interval.

PMID- 8547208
TI  - Is contractility depressed in the failing human heart?
AB  - Is contractility depressed in the failing human heart? The question must be
      approached in a stringent manner. Myocardium from failing human hearts has been
      shown to generate normal physiological force under the ideal conditions of low
      stimulation and an adequate energy supply. Nevertheless, even when subjected to
      physiologically conducive conditions, failing myocardium experiences a slowed
      relaxation, adversely affecting the diastolic properties of the heart. In
      addition, experiments have shown that increasing the contraction rates of failing
      hearts clearly results in lowered force and pressure evolution. This information
      indicates a decrease in contractile reserve in both a systolic and diastolic
      sense. Not surprisingly, the term end-stage heart failure becomes questionable
      when applied to myocardium obtained from patients undergoing cardiac
      transplantation. A number of studies involve such myocardium from feasible
      regions of the heart perfused within ideal physiological conditions yielding, at
      times, nonfailing performance. Therefore, it becomes imperative to bear in mind
      the role of such myocardium within the framework of the entire diseased heart.

PMID- 8547209
TI  - Effects of 12 weeks of ramipril treatment on the quality of life in patients with
      moderate congestive heart failure: results of a placebo-controlled trial.
      Ramipril Study Group.
AB  - The assessment of quality of life (QoL) has become recognized as an important
      tool for evaluating heart failure therapy. The angiotensin-converting enzyme
      inhibitor ramipril (mean dose 8 mg) was evaluated in 223 patients with moderate
      chronic congestive heart failure at 24 centers in 4 Nordic countries following a
      randomized, double-blind, placebo-controlled, parallel group design. The follow
      up period was 12 weeks. QoL was evaluated using a questionnaire with 47 items,
      including the disease-specific Severe Heart Failure Questionnaire, the Sleep
      Dysfunction Scale, and the Psychological General Well-Being Index. In both
      treatment groups the total score increased from baseline to 12 weeks for both the
      Severe Heart Failure Questionnaire and for the Psychological Well-Being Index,
      reflecting relief of symptoms and improved well-being. However, no significant
      differences between the placebo and ramipril groups could be detected. Only a
      trend toward improvement in sleep on ramipril compared with placebo therapy was
      observed. In conclusion, in this placebo-controlled trial no significant effects
      of 12-week ramipril treatment of QoL could be demonstrated in patients with
      moderate congestive heart failure.

PMID- 8547210
TI  - Hemodynamic and antiischemic effects of intravenous elgodipine, a new
      dihydropyridine calcium channel blocker, in patients with chronic stable angina.
AB  - Elgodipine is a new second-generation dihydropyridine calcium antagonist. Its
      hemodynamic and antiischemic properties were evaluated in a single-blind, placebo
      controlled trial in 22 males with chronic stable angina. Coronary artery disease
      was angiographically confirmed. Measurements were performed with a Swan-Ganz
      thermodilution catheter during a 30-minute period of rest and before the end of a
      4-minute bicycle exercise test at maximum individual workload, both with placebo
      (IV infusion of 5 ml saline over 30 minutes) and elgodipine (10 micrograms/kg/2
      min bolus IV, then IV infusion of 1 micrograms/kg/min for 28 minutes. Elgodipine
      caused very similar hemodynamic changes at rest and during exercise. Its major
      hemodynamic modification was the marked decrease in systemic vascular resistance,
      which was accompanied by an increase in cardiac index and stroke volume. Mean
      arterial blood pressure was slightly reduced, whereas the opposite small increase
      in heart rate meant that the double product remained unchanged. Contrary to
      resting conditions, pulmonary capillary wedge pressure, pulmonary artery
      pressures, pulmonary vascular resistance, and mean right atrial pressure remained
      normal or increased to a lesser extent during exercise after elgodipine. After
      elgodipine ischemic ST depression during exercise was diminished, and 11 of 16
      assessable patients remained free from angina pectoris. We conclude that
      elgodipine is an efficacious antianginal drug. Its major mechanism of action is
      lowering of systemic vascular resistance. Thus elgodipine improves systolic
      cardiac function in patients with chronic stable angina and may delay the onset
      of ischemic diastolic dysfunction during exercise, as indicated by a normal left
      ventricular end-diastolic pressure (LVEDP). The data also suggest an improvement
      in coronary blood flow during exercise.

PMID- 8547211
TI  - Effects of beraprost sodium, a new prostaglandin I2 analog, on parameters of
      hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional
      angina.
AB  - The purpose of this study was to investigate the effects of beraprost sodium, a
      stable prostacyclin analog, on the parameters of hemostasis, fibrinolysis, and
      myocardial ischemia in patients with exertional angina. Thirty-one patients with
      exertional angina who had significant organic coronary artery stenosis in at
      least one of the three major coronary arteries were selected. All patients
      underwent quantitative exercise thallium-201 emission computed tomography before
      and 1 month after 120 micrograms per day of beraprost sodium administration.
      Before exercise, blood samples were collected from 8:30 a.m. to 9:30 a.m. after
      the patients had been lying in bed undisturbed for at least 10 minutes. Plasma
      platelet factor 4 (PF4), fibrinopeptide A (FPA), tissue plasminogen activator
      antigen (t-PA), and plasminogen activator inhibitor-1 activity (PAI-1) were
      measured. There were no significant differences in exercise parameters on both
      exercise tests. However, both the extent and severity scores of ischemia were
      significantly aggravated (p < 0.05 for both) during beraprost sodium
      administration. Plasma FPA levels decreased significantly during beraprost sodium
      administration (p < 0.01). Likewise, plasma PF4 levels decreased significantly
      during beraprost sodium administration (p < 0.05). As for plasma t-PA antigen
      levels, there was no significant difference before versus during beraprost sodium
      administration. Plasma PAI-1 activity levels decreased significantly during
      beraprost sodium administration (p < 0.05). The results indicate that beraprost
      sodium has strong antithrombogenic properties. However, its aggravation of
      myocardial ischemia may limit clinical usage.

PMID- 8547212
TI  - Digoxin and mortality in survivors of acute myocardial infarction: observations
      in patients at low and intermediate risk. The SPRINT Study Group. Secondary
      Prevention Reinfarction Israeli Nifedipine Trial.
AB  - Controversy surrounds the safety of digoxin use in patients recovering from acute
      myocardial infarction. Previous observations yielded contradictory conclusions.
      To determine whether digoxin therapy is associated with increased mortality in
      patients recovering from acute myocardial infarction, we analyzed data from 1731
      survivors of acute myocardial infarction enrolled in the Secondary Prevention
      Reinfarction Israeli Nifedipine Trial (SPRINT), from which patients with severe
      heart failure were excluded. At the time of hospital discharge, 175 patients
      (10%) were taking digoxin. Mortality over 1 year after infarction was
      significantly higher in patients treated with digoxin than in patients who were
      not receiving digoxin [27 of 175 (15%) vs. 60 of 1556 (4%); p < 0.0001]. Digoxin
      administration was associated with increased mortality in several subsets of
      patients. Since patients treated with digoxin had baseline characteristics
      predictive of mortality more frequently than their counterparts, we adjusted for
      these differences. Multivariate analysis performed by the Cox proportional
      hazards model identified treatment with digoxin as an independent determinant
      associated with increased death during the first year after myocardial infarction
      [relative risk (RR) 2.8; 90% confidence interval (CI) 1.8-4.2]. Subgroup
      multivariate analysis indicated digoxin as an independent predictor of first year
      death in 464 patients who developed heart failure during their hospital stay (RR
      2.3; 90% CI 1.3-4.0), as well as among 1267 patients who did not (RR 3.4; 90% CI
      1.7-6.9). The present study suggests a significant excess mortality associated
      with digoxin therapy after myocardial infarction. The increased mortality risk
      may be related to unidentified variables associated with the severity of disease
      in patients treated with digoxin. However, our findings raise concern that the
      administration of digoxin may contribute to increased mortality in survivors of
      acute myocardial infarction.

PMID- 8547214
TI  - Methylergometrine-induced myocardial ischemia in a previously asymptomatic
      premenopausal woman.

PMID- 8547213
TI  - Interaction of antiplatelet drugs in vitro: aspirin, iloprost, and the nitric
      oxide donors SIN-1 and sodium nitroprusside.
AB  - The interaction of three antiplatelet drugs was studied in vitro: aspirin, an
      inhibitor of the cyclooxygenase pathway of platelet activation; iloprost, a
      stable analog of prostacyclin that increases platelet cAMP; and the nitrix oxide
      donors SIN-1 and sodium nitroprusside (SNP), which both raise platelet cGMP.
      Platelet adhesion and aggregation evoked by collagen/ADP were measured in
      anticoagulated blood under physiological flow conditions using the new
      Thrombostat. Aggregation was also measured in platelet-rich plasma (PRP) upon
      stimulation by a low (2.5 micrograms/ml) and high (20 micrograms/ml) dose of
      collagen, ADP, or thrombin-receptor activating peptide (TRAP). We found a
      synergism between iloprost and aspirin in inhibiting platelet
      adhesion/aggregation in flowing blood and aggregation of PRP stimulated by
      collagen. The mean inhibitory concentrations (IC50) of iloprost in the presence
      of aspirin were much lower (0.7 nM and 0.5 nM in flowing blood and low-dose
      collagen-stimulated PRP, respectively) than in the absence of aspirin (3 and 3.6
      nM, respectively). Synergism between SIN-1 and aspirin was observed in inhibiting
      platelet activation in flowing blood but was much less pronounced in inhibiting
      collagen-induced aggregation of PRP. SIN-1/SNP and iloprost synergistically
      inhibited the aggregation of PRP induced by collagen as well as platelet
      adhesion/aggregation in blood. We found that two protein substrates of cAMP- and
      cGMP-dependent protein kinases, rap1B and a 50 kD protein, were associated with
      the functional synergism between SIN-1 and iloprost and were synergistically
      phosphorylated by platelet treatment with both iloprost and SIN-1. Platelet
      inhibition by SIN-1, iloprost, and aspirin was synergistic when measured in
      blood. In contrast, only additive effects of SIN-1 and iloprost were observed
      when platelet aggregation was measured in aspirin-treated PRP stimulated by ADP,
      TRAP, or collagen. Our study defines the basis for a more effective antiplatelet
      therapy using a combination of cGMP- and cAMP-elevating and cyclooxygenase
      inhibiting drugs. The results also emphasize the importance of using various
      methods for the evaluation of antiplatelet drugs.

PMID- 8547215
TI  - Elucidation of a signaling pathway induced by FGF-2 leading to uPA gene
      expression in NIH 3T3 fibroblasts.
AB  - Fibroblast growth factors (FGFs) play a role in biological processes such as cell
      growth and development, angiogenesis, and wound healing. Several genes have been
      shown to be induced by FGFs, but the underlying mechanisms have not been
      elucidated. We investigated the effect of FGF-2 (basic FGF) on the urokinase-type
      plasminogen activator (uPA) gene in NIH 3T3 fibroblasts. We found that the uPA
      gene is transcriptionally induced by FGF-2 as well as by 12-O
      tetradecanoylphorbol-13 -acetate involving a PEA3/AP1 element located 2.4 kb
      upstream of the transcription initiation site; neither induction requires ongoing
      protein synthesis. Unlike 12-O-tetradecanoylphorbol-13-acetate induction, FGF-2
      induction was not impaired by protein kinase C down-regulation. Analyses of
      various signaling molecules by Western blotting, extracellular signal-regulated
      kinase (ERK) activity assays, and transient transfection assays (cotransfection
      of a uPA-reporter gene construct with expression vectors for wild-type or
      dominant negative type of these molecules or for ERK-specific protein phosphatase
      MKP-1) showed that a Ras/Raf-1/MEK/ERK-2/JunD pathway is induced by FGF-2 and 12
      O-tetradecanoylphorbol-13-acetate, leading to the activation of the uPA gene.

PMID- 8547216
TI  - Expression of fibroblast growth factor receptors flg and bek during hepatic
      ontogenesis and regeneration in the rat.
AB  - Fibroblast growth factors (FGFs) mediate their cellular responses through
      specific cell surface receptors. Previous studies have indicated that acidic FGF
      is involved in liver regeneration and hepatic differentiation via the stem cell
      compartment, as well as in liver development (Marsden et al., Lab. Invest. 67:427
      433, 1992). To further define the role of acidic FGF and its receptor systems in
      the liver, we examined the expression and cellular localization of FGF receptor-1
      (flg) and FGF receptor-2 (bek) in the liver by Northern blot analysis and in situ
      hybridization techniques during liver regeneration, hepatic differentiation, and
      ontogenesis. In the normal adult liver, flg is absent in hepatocytes, whereas a
      low level of bek can be detected. The transcripts for bek increased, while flg
      exhibited little change during liver regeneration after partial hepatectomy. Both
      flg and bek were expressed at high levels in the developing liver. flg was
      expressed at a high level in embryonic liver and further increased after birth,
      whereas a significant increase of bek occurred at the postnatal stage of liver
      development. In the 2-acetylaminofluorene/partial hepatectomy model, both flg and
      bek are expressed at high levels during the period of active proliferation and
      differentiation of oval cells. In situ hybridization showed that flg was mainly
      localized in oval cells, whereas bek was highly expressed in both oval and Ito
      cells. The data suggest that bek is involved in the proliferation of mature
      hepatocyte proliferation during liver regeneration, while flg is characteristic
      of primitive hepatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547217
TI  - Chronic exposure of cultured transformed mouse epidermal cells to transforming
      growth factor-beta 1 induces an epithelial-mesenchymal transdifferentiation and a
      spindle tumoral phenotype.
AB  - Transformed mouse epidermal keratinocytes of the cell line PDV, when cultured
      under the presence of transforming growth factor-beta 1 (TGF-beta 1), escaped the
      block of growth exerted by this factor in normal keratinocytes and underwent
      marked changes in cell differentiation. TGF-beta 1 induced disruption of
      epithelial interactions, dispersion of cells, increased local movement, and
      conversion to a fibroblast-like morphology. These changes were reversible and
      correlated with down-regulation of epithelial protein markers such as E-cadherin
      and cytokeratins and upregulation of vimentin. TGF-beta 1-treated cells with a
      fibroblast-like phenotype induced spindle cell carcinomas upon transplantation in
      athymic nude mice, whereas untreated PDV cells or fusiform cells reverted to the
      epithelial phenotype and produced well-differentiated squamous cell carcinomas.
      Nontumorigenic immortalized epidermal keratinocytes, when grown under the
      presence of TGF-beta 1, did not transdifferentiate to a mesenchymal phenotype,
      their proliferation was blocked, and cells finally died. These results suggest a
      role of TGF-beta 1 in the progression of squamous carcinoma cells to spindle
      carcinomas in mouse skin carcinogenesis.

PMID- 8547218
TI  - The product of Zfp59 (Mfg2), a mouse gene expressed at the spermatid stage of
      spermatogenesis, accumulates in spermatozoa nuclei.
AB  - We have described previously three mouse multifinger coding genes (C. Passananti
      et al., Proc. Natl. Acad. Sci. USA, 86: 9417-9421, 1989). We have analyzed the
      expression of one of them, termed Mfg2 and renamed Zfp59, and demonstrated that
      Zfp59 mRNA and its translation product are present in specific stages of mouse
      spermatogenesis. The predicted amino acid sequence of the Zfp59 protein has been
      found to consist of 16 zinc-finger motifs clustered at the COOH terminus and
      subdivided into two groups by a degenerate finger motif. At its NH2 terminus,
      Zfp59 shares with other members of the zinc finger gene family two additional
      conserved amino acid modules A and B, described as either FAX, KRAB, or FPB
      domains. By means of Northern blot, Western blot analysis, and
      immunohistochemical localization, Zfp59 mRNA and its translation product were
      shown to be synthesized specifically during the postmeiotic phase of male germ
      line differentiation. By immunoelectron microscopy, the Zfp59 protein has been
      shown to accumulate in the nuclei of mature sperms in association with the
      nuclear matrix.

PMID- 8547219
TI  - Inhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by
      mutant p53.
AB  - The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell
      cycle. The WAF1/Cip1 protein binds to the cyclin-dependent kinase complexes and
      inhibits the kinase activity that is required for cell cycle progression. We
      investigated the expression of WAF1/Cip1 protein in 14 glioblastoma cell lines
      and found that WAF1/Cip1 expression was detectable in many of the cell lines,
      even when mutant p53 was present. We also showed that WAF1/Cip1 protein level was
      very low in LN-Z308 cells that do not express endogenous p53. Transfection of the
      wild-type p53 into this cell line activated WAF1/Cip1 expression and inhibited
      cell growth. In contrast, transfection of the p53 mutant 248Trp failed to
      activate WAF1/Cip1 expression. Transfection of WAF1/Cip1 alone also inhibited LN
      Z308 cell proliferation. However, cotransfection of the p53 mutant 248Trp with
      WAF1/Cip1 attenuated the growth-suppression effect of WAF1/Cip1. Our analysis
      with Western blot showed that the levels of cyclin E increased in cells
      transfected with p53 mutants. We conclude that p53 mutants may counter the
      negative regulators, such as WAF1/Cip1, by the elevation of positive cell cycle
      regulators, and the presence of WAF1/Cip1 in tumor cells is not sufficient for
      growth inhibition.

PMID- 8547220
TI  - Conditional binding to and cell cycle-regulated inhibition of cyclin-dependent
      kinase complexes by p27Kip1.
AB  - Mammalian cultures primarily regulate cell cycle traverse during G1. For
      progression through G1 and commitment to DNA synthesis, the activity of a family
      of proteins, the cyclin-dependent kinases (cdks), is required. There are two
      primary regulatory portions of G1: (a) the G0-G1 transition, which allows entry
      into G1; and (b) the G1-S transition, promoting entry to DNA synthesis and
      commitment to cell division. In the present manuscript, we provide evidence for
      cross-talk between these two cell cycle transitions. Extracts prepared from
      quiescent mouse mammary epithelial cells are shown to act in a dominant manner to
      specifically inhibit the histone H1 kinase activity of preformed/active cdk2,
      cdk4, cyclin A, or cyclin E complexes from G1-S cell extracts. The inhibitory
      activity arises as cells enter quiescence and decreases once cultures are
      stimulated to begin G1 traverse and endogenous cdk activity becomes evident. This
      activity is associated with the regulated binding of the cdk inhibitor p27Kip1 to
      cyclin A/cdk2 kinase complexes upon mixing of the extracts. Removal of p27Kip1
      from the quiescent cell extract specifically abolishes the inhibitory effect. The
      inhibitory activity and p27Kip1 binding in vitro depend on incubation of the
      extracts at physiological temperature or the presence of a reducing agent. The
      results suggest an interplay between the acquisition of quiescence, cdk activity,
      and G1 traverse.

PMID- 8547222
TI  - Induction of cell differentiation potentiates apoptosis triggered by prior
      exposure to DNA-damaging drugs.
AB  - At the end of their life span, differentiated cells die by apoptosis. Subsets of
      cells also die, in some cell systems, shortly after exposure to differentiating
      agents. This suggests that early during differentiation the cells may undergo
      "priming," during which synthesis and/or activation and accumulation of effectors
      of apoptosis occurs. The objective of the present study was to test the
      hypothesis that the signal for apoptosis provided by DNA-damaging drugs given
      prior to induction of differentiation will be more effective in triggering
      apoptosis than when given following induction of differentiation. Human
      promyelocytic HL-60 cells were treated with the topoisomerase I inhibitor
      camptothecin, the alkylating agent nitrogen mustard, or 5'-azacytidine, an
      antimetabolite affecting predominantly RNA metabolism. Following drug removal,
      the cells were postincubated with n-butyrate, which induces differentiation of HL
      60 cells along the monocytic pathway, or with all-trans-retinoic acid, which
      triggers myelocytic differentiation. Multiparameter flow cytometry using two
      different methods of analysis of apoptosis-associated DNA breakage in situ, as
      well as evaluation of cell morphology and DNA gel electrophoresis, were used to
      ascertain the mode of cell death. Increases of 100-200% in the percentage of
      apoptotic cells were seen when cells were first treated with camptothecin or
      nitrogen mustard, followed by n-butyrate or retinoic acid, compared to the
      combined percentage of apoptotic cells when these agents were used
      individually.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547221
TI  - Apoptosis in 7-hydroxystaurosporine-treated T lymphoblasts correlates with
      activation of cyclin-dependent kinases 1 and 2.
AB  - 7-Hydroxystaurosporine (UCN-01) is a potent inhibitor of protein kinase C (PKC)
      isozymes alpha, beta, and gamma [Seynaeve et al., Mol. Pharmacol, 45: 1207-1214,
      1994] that also has antitumor effects in vivo. To determine whether inhibition of
      PKC can be related to inhibition of cell growth with induction of apoptosis, we
      compared the effects of UCN-01 to those of the highly selective
      bisindolylmaleimide PKC antagonist GF 109203X in leukemic T-cell lines. Both
      compounds potently inhibited PKC activity when added to T-cell membrane
      preparations and reversed phorbol ester-induced c-fos gene expression in intact
      cells. However, whereas UCN-01 potently inhibited growth of Jurkat, Molt-3, Molt
      4, and Hut-78 cells (IC50 = 20-65 nM, irreversible after 24 h of exposure), GF
      109203X had IC50s for cell growth of 3.6-5.0 muM. Less than 3 h after addition,
      UCN-01 but not GF 109203X-treated cells displayed loss of cells with G2-M DNA
      content, appearance of a hypodiploid DNA fraction, and evidence of
      internucleosomal DNA fragmentation. Six h after treatment, cells appeared to
      accumulate with S-phase DNA content. These effects correlated with selective UCN
      01 but not GF 109203X-induced decrease in total and tyrosine phosphorylation of
      cyclin-dependent kinases (cdks) 1 and 2, and with increases in the histone H1
      kinase activities of cdk1 and cdk2. UCN-01 was relatively less potent in
      inhibition of properly activated cdk1 and cdk2 when added in vitro to H1 kinase
      assays (IC50 = 1000 and 600 nM, respectively). We conclude that inhibition of PKC
      alone is not sufficient to account for the actions of UCN-01 and are led to the
      hypothesis that inappropriate cdk activation either correlates with or actually
      mediates cell growth inhibition with apoptosis in T lymphoblasts exposed to UCN
      01.

PMID- 8547223
TI  - Insulin regulates expression of c-fos and c-jun and suppresses apoptosis of lens
      epithelial cells.
AB  - This study investigates whether insulin (a differentiation factor for lens
      epithelial cells) acts as a survival factor. In the absence of insulin, 6-day
      embryonic chicken lens epithelial explants undergo apoptosis as shown by changes
      in cell morphology, DNA fragmentation, and loss of trypan blue exclusion. Insulin
      inhibits these changes and promotes survival of the cells. Aurintricarboxylic
      acid suppresses the apoptosis of lens explants. In contrast to 6-day embryonic
      explants, 19-day embryonic explants survive in the absence of insulin, presumably
      due to an endogenous survival factor. To explore the mechanism of the action of
      insulin as a survival factor for 6-day embryonic lens explants, we compared the
      pattern of cell cycle markers (c-fos, c-jun, c-myc, p53, histone H3, thymidine
      kinase, and cyclin B) in both apoptotic and differentiating lens explants. In the
      presence of insulin, the expression of c-fos and c-jun was down-regulated after
      an initial induction. Expression of these genes was also induced in the absence
      of insulin, but mRNA levels remained elevated as the cells underwent apoptosis.
      In contrast, expression of c-myc, p53, histone H3, thymidine kinase, and cyclin B
      showed only minor differences in differentiating and apoptotic cells. Since c-fos
      and c-jun have been shown to play a role in apoptosis in other cell types, the
      ability of insulin to regulate expression of these genes may be central to its
      ability to act as a survival factor for lens epithelial cells.

PMID- 8547224
TI  - Serum response element and flanking sequences mediate the synergistic
      transcriptional activation of c-fos by 12-O-tetradecanoylphorbol-13-acetate and
      cholera toxin in AKR-2B cells.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) and cholera toxin have been shown
      previously to act synergistically to stimulate traverse of G0-G1 and entry into S
      phase in quiescent mouse fibroblasts. These agents also have a synergistic effect
      on the induction of the endogenous c-fos gene, as well as a transfected reporter
      construct containing the mouse fos promoter/enhancer region from -397 to +1
      cloned upstream of luciferase. A detailed mutational analysis of the c-fos
      regulatory region revealed that the synergy between TPA and cholera toxin
      requires multiple discrete elements, including the binding sites for the serum
      response factor (-308 to -299), p62/Elk-1 (-316 to -309), on the 5' side of the
      serum response element, and a CCAAT or E box-binding protein(s) on the 3'
      flanking side of the serum response element (-303 to -295 or -297 to -292,
      respectively). The putative cyclic AMP response element (-65 to -58), shown to be
      activated in a number of cell types after increases in cyclic AMP levels,
      mediated an induction by TPA but not by cholera toxin in AKR-2B cells, and was
      not required for the synergistic transactivation induced by the combination of
      TPA and cholera toxin.

PMID- 8547225
TI  - Retrovirus-mediated transfer of nuclear factor-kappa B subunit genes modulates I
      kappa B alpha and interferon beta expression.
AB  - Nuclear factor (NF)-kappa B proteins regulate the transcription of numerous genes
      involved in the immune response, transcription control, and viral pathogenesis.
      To examine the effect of ectopic expression of NF-kappa B proteins on DNA-binding
      activity and gene expression, individual NF-kappa B subunit genes were introduced
      into NIH 3T3 cells via retrovirus-mediated gene transfer. Expression of NF-kappa
      B subunits RelA (p65), NF-kappa B1 (p105), NF-kappa B2 (p100), and c-Rel
      increased the basal level of nuclear NF-kappa B DNA binding in NIH 3T3 cells,
      whereas expression of delta RelA (p65 delta) and NF-kappa B2 (p52) subunits did
      not affect basal level activity. Tumor necrosis factor-alpha treatment of the NF
      kappa B-expressing cells stimulated the induced level of DNA-binding activity,
      reflecting interaction between endogenous murine and transfected human NF-kappa B
      proteins. Interestingly, expression of RelA (p65), c-Rel, NF-kappa B1 (p105), NF
      kappa B2 (p100), and NF-kappa B2 (p52) subunits increased I kappa B alpha protein
      levels from 3- to 30-fold, indicating that one mechanism to compensate for the
      increased expression of NF-kappa B proto-oncogenes was to increase the synthesis
      and/or stability of the regulatory I kappa B alpha protein. In addition,
      overexpression of RelA (p65), c-Rel, NF-kappa B2 (p100), and NF-kappa B2 (p52)
      altered the induction kinetics of IFN-beta mRNA after Sendai virus infection,
      whereas overexpression of NF-kappa B1 (p105) dramatically decreased IFN-beta mRNA
      induction.

PMID- 8547226
TI  - Induction of differentiation-regulated transcription factor Oct-6 specifically
      accompanies major histocompatibility complex class I down-regulation by E1A of
      oncogenic adenovirus type 12.
AB  - The E1A genes from adenovirus (Ad) types 5 and 12 share the capacity to cooperate
      with a second oncogene to transform primary rodent cells in vitro. However, only
      Ad12-transformed cells are oncogenic in immunocompetent rodents, an event that
      requires conserved region 3 (CR3) of E1A to be intact. Ad12-induced
      tumorigenicity correlates with the E1A-CR3-dependent down-modulation of MHC class
      I transcription, contributing to escape from CTL-mediated immune surveillance.
      Expression of MHC class I antigens is also lacking in undifferentiated embryonal
      carcinoma cells. In these cells, MHC class I expression increases during
      differentiation in a process possibly involving octamer-binding proteins. We
      found that both nononcogenic and oncogenic Ad-transformed cells contained the
      ubiquitously expressed factor Oct-1. In contrast, only oncogenic Ad12-transformed
      cells that are derived from primary cell cultures expressed an additional octamer
      binding factor, which we identified as Oct-6. The induction of Oct-6 expression
      was at the RNA level and was found to require an intact CR3 domain in Ad12 E1A.
      Like MHC class I expression, Oct-6 expression was not affected in already
      established cell lines expressing Ad12 E1A. The presence of Oct-6 in Ad12
      transformed cells correlated with an increase in octamer-dependent transcription
      of a reporter gene, relative to Ad5-transformed cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8547227
TI  - Modulation of E-cadherin localization in cells expressing wild-type E1A 12S or
      hypertransforming mutants.
AB  - The adenovirus E1A 12S gene can immortalize primary epithelial cells such that
      they retain expression of epithelial cell characteristics. E1A 12S can also
      cooperate with an activated ras oncogene to cause tumorigenic transformation of
      primary cells. Specific substitution and deletion mutants of E1A 12S cooperate
      more efficiently with ras to produce foci with a hypertransformed phenotype,
      wherein the cells are less differentiated and exhibit invasive properties. Loss
      of epithelial differentiation in carcinomas is often a consequence of reduced
      intercellular adhesion involving loss of a functional cell-cell adhesion
      molecule, E-cadherin. Therefore, expression of E-cadherin was analyzed in mock
      infected primary epithelial cells, cells expressing E1A 12S protein, and in
      hypertransformed cells. Primary epithelial cells express E-cadherin and correctly
      localize it to the cell-cell junctions, as detected by immunofluorescence. The
      level of E-cadherin expression decreases with time in culture. Primary cells
      expressing the E1A 12S protein maintain the expression and correct localization
      of E-cadherin. This effect of E1A 12S on E-cadherin expression is not at the
      transcriptional level. Immortalized cells expressing the 12S protein and primary
      epithelial cells transformed with the E1A 12S gene and ras continue to express E
      cadherin at the cell-cell junctions. In contrast to the 12S-immortalized and wild
      type transformed cells, hypertransformed cells are defective for localization of
      E-cadherin and exhibit altered subcellular distribution of E-cadherin, as
      detected by immunoprecipitation with an anti-E-cadherin antibody. Furthermore,
      the aberrant localization exhibited by the hypertransformed cells can be overcome
      by superinfection of the hypertransformed cells with a virus expressing the E1A
      12S cDNA or treatment with retinoic acid. Thus, the E1A 12S protein appears to
      act as a differentiation factor to maintain the differentiated characteristics of
      epithelial cells.

PMID- 8547228
TI  - Transformation of erythroid progenitors by viral and cellular tyrosine kinases.
AB  - Recently, two different normal avian erythroid progenitors were described. They
      differ in the receptor tyrosine kinases they express and in their ability to
      undergo self-renewal in culture. A common progenitor, termed stem cell factor
      (SCF) progenitor, expresses the receptor for avian SCF c-Kit, and undergoes short
      term self-renewal when grown in the presence of avian SCF. A second progenitor,
      referred to as SCF/transforming growth factor-alpha progenitor, coexpresses c-Kit
      and the avian epidermal growth factor receptor homologue c-ErbB. These
      progenitors undergo sustained self-renewal when grown in the presence of
      transforming growth factor-alpha plus estradiol. The phenotype of the normal
      SCF/transforming growth factor-alpha progenitors closely corresponded to that of
      erythroid cells transformed by the tyrosine kinase oncogenes v-erbB or v-sea.
      This suggested that these cells, but not the SCF progenitors, would be the target
      cells for erythroblast transformation by these oncogenes. However, we demonstrate
      that both progenitor cells can be transformed by the v-erbB and v-sea oncogenes
      and also by the ligand-activated proto-oncogene product c-ErbB. We conclude that
      the target cell specificity of certain tyrosine kinase oncoproteins for erythroid
      cells is a reflection of their ability to provide signals for self-renewal that
      normally emanate from the endogenous c-ErbB protein.

PMID- 8547229
TI  - Antigenic characteristics and cDNA sequences of HLA-B73.
AB  - The cDNA sequence and serological data for HLA-B73 are reported. Anti-B73 sera
      are found relatively frequently, considering the rarity of the antigen. It was
      noted early that in some cases the antibodies in sera of multiparous women did
      not react with the eliciting cells (fathers) and thus all behaved as a naturally
      occurring antibody. We report on 18 B73 antisera found during the screening of
      55,000 Danish sera. Only one of the 17 stimulators typed also had the B73 tissue
      type. Ten of the stimulators had antigens from the B7 CREG (B7, B22, B27, B42,
      B67, B73), whereas none of the responders had such tissue types. In seven cases
      the serum was not able to react with the stimulator's lymphocytes in a
      cytotoxicity assay and in four cases the stimulator lymphocytes could not deplete
      the anti-B73 activity from the serum in absorption experiments. The cDNA of B73
      was expressed correctly in COS cells and was recognized on the cell surface by a
      monospecific serum. The alpha 1 alpha 2 domains of B73 are most similar to those
      of the HLA-B22 family. Interestingly, the alpha 3 and transmembrane domains of
      HLA-B73 are not standard human domains, but are most similar to the corresponding
      domains of some gorilla and chimpanzee HLA-B genes.

PMID- 8547230
TI  - Deletion of the 3' splice site of the leader-variable region intron of
      immunoglobulin heavy chain genes induces a direct splicing of leader to constant
      region, resulting in the production of truncated mu-chains.
AB  - An Abelson virus-transformed immature B cell line, AT8-1-12-5-2, produced
      truncated mu-chains. Sequencing analysis of the VHDJH complex on the expressed H
      chain allele revealed the deletion of 75 nucleotides that involved leader
      variable region intron and the 5' end of the variable region, which resulted in
      the loss of the 3' splice site of leader-variable region intron. Sequence studies
      of a leader- and CH1-containing cDNA clone showed that leader region was directly
      spliced to the CH1 exon, resulting in the production of the truncated mu-chains
      without variable portion. Our results demonstrated for the first time that the
      only loss of the 3' splice site of leader-variable region intron could induce an
      aberrant splicing between leader and constant region.

PMID- 8547231
TI  - At least four MHC class I genes are transcribed in the horse: phylogenetic
      analysis suggests an unusual evolutionary history for the MHC in this species.
AB  - Nineteen horse MHC class I specificities have been serologically identified
      previously at a single locus (ELA-A), and two other specificities appear to be
      coded at other loci. Biochemical studies indicate that there are at least two
      expressed loci. In order to establish the number of transcribed horse MHC class I
      genes, we made a cDNA library from a heterozygous animal (ELA-A3/A7), and
      screened for positive clones using a bovine class I probe. More than 200 class I
      clones were isolated in this way, and so far seven unique full length sequences
      have been identified. All of the sequences are predicted to code for surface
      expressed, functional molecules. The number of different sequences identified
      demonstrate that at least four genes are transcribed, although variations in
      transmembrane length (which is generally conserved in class I loci) suggest that
      five genes could be represented. Evolutionary analysis of these sequences (and
      two additional sequences known to represent different horse class I loci) reveals
      no firm relationships, such that the division between the different loci cannot
      be discerned. These results suggest an unusual evolutionary history for the horse
      MHC, the precise nature of which may be revealed only following further cross
      species comparisons.

PMID- 8547232
TI  - A novel TaqI/DQA RFLP associated with HLA-DR9, DQ9 (DQA1*0302).
AB  - A new TaqI/DQA restriction fragment length polymorphism (RFLP) has been found in
      two Spanish Caucasoid individuals. The novel polymorphic fragment has a relative
      mobility of 4.2 kb and is associated with an HLA-A2,Cw*1401,B51,DR9,DR53,DQ9
      haplotype. Nucleotide sequence analysis indicates that individuals showing this
      RFLP pattern do not carry a new DQA1 allele, but that (DQA1*0302) commonly
      observed in DR9,DQ9 haplotypes. The new RFLP seems to be a locally restricted
      marker of uncertain origin.

PMID- 8547233
TI  - Methylation patterns of I epsilon region in B cells stimulated with interleukin 4
      and Epstein-Barr virus in patients with a high level of serum IgE.
AB  - Human IgE synthesis requires the presence of both interleukin 4 (IL-4) and T
      cells. However, it is not clear what role IL-4 and T-cells play in the induction
      of IgE synthesis at the level of gene regulation. B cells that were obtained from
      patients with a high level of serum IgE and from healthy donors were immortalized
      by Epstein-Barr virus. We examined IgE production of these B cells stimulated
      with IL-4. Supernatant IgE levels of patient's B cells cultured with or without
      IL-4 were higher than those of healthy donor's B cells. Our results indicated
      that B cells stimulated with IL-4 from patients produced IgE, germline C epsilon
      transcript, and S mu S epsilon recombination. The germline C epsilon transcript
      was dose-dependently induced in the presence of IL-4 and related to the
      supernatant IgE level. In B cell stimulated with IL-4 that were obtained from
      patients, (some of the) DNA near or within the I epsilon region was (already
      partly) unmethylated, unlike those from healthy donors, and there was a loss of
      methyl groups of the DNA upon the addition of IL-4 in B cells from both patients
      and normal donors. IgE synthesis of B cells stimulated with IL-4 in patients with
      a high level of serum IgE is due to an accessibility in the immunoglobulin heavy
      chain isotype switch, and this may reflect the accessibility in synthesis of
      germline C epsilon transcript, which may be caused by the increase of opening
      chromatin structures because of their unmethylation in the I epsilon region.

PMID- 8547235
TI  - Rapid characterization of HLA class I alleles by gene mapping using ARMS PCR.

PMID- 8547234
TI  - PVU II polymorphism of LST-1 (leucocyte specific transcript-1) in type I diabetes
      mellitus, Graves' disease and healthy controls.
AB  - The polymorphism of the LST-1 gene (the human homologue of the mouse B144 gene)
      can be identified by Pvu II restriction enzyme digestion. We investigated the
      contribution of this RFLP to disease susceptibility in 117 patients with type I
      diabetes mellitus (IDDM), 110 with Graves' disease (GD) and 93 healthy controls.
      The distribution of the different LST-1 alleles (LST-1*1:1323 bp, LST-1*2:610
      bp/713) was similar among IDDM and GD patients as well as in controls. The
      combination of DQA1*0501, DQB1*0201 and DQB1*0301, all predisposing to endocrine
      autoimmune disease, with LST-1*1 or LST-1*2 was not increased in patients.
      Analysis of two informative families with IDDM demonstrated cosegregation of DQA1
      and DQB1 alleles with LST-1 alleles. No association of LST-1 polymorphisms with
      IDDM nor GD could be demonstrated.

PMID- 8547236
TI  - Identification of tyrosine 489 in the carboxy terminus of the Tpr-Met oncoprotein
      as a major site of autophosphorylation.
AB  - The Met receptor tyrosine kinase is the receptor for hepatocyte growth
      factor/scatter factor. HGF/SF is a multifunctional cytokine that can stimulate
      proliferation, motility, and morphogenesis in epithelial and endothelial cells.
      Oncogenic activation of the Met receptor occurs through a genomic rearrangement
      that generates a hybrid protein in which tpr sequences are directly fused amino
      terminal to the met receptor kinase domain. The resultant Tpr-Met hybrid protein
      possesses tyrosine kinase activity, is constitutively phosphorylated on tyrosine
      residues in vivo, and transforms fibroblasts in culture. We have identified two
      tyrosine residues within the catalytic domain of the Tpr-Met oncoprotein (Y365,
      Y366) and Met receptor (Y1234, Y1235) that are phosphorylated and essential for
      both the catalytic and biological activity of the oncoprotein and receptor.
      However, a detailed analysis of phosphorylation in these proteins has not been
      undertaken. In order to determine the sites of tyrosine phosphorylation in the
      Tpr-Met oncoprotein, in vitro mutagenesis, phosphopeptide mapping, and
      dephosphorylation protection assays were performed. Here we identify that a
      single tyrosine (Y489) in the carboxy terminus of the Tpr-Met oncoprotein is
      highly phosphorylated and is essential for biological activity. In contrast,
      additional tyrosines (Y482, Y498) located in the carboxy terminus are not
      phosphorylated at detectable levels and are not essential for the biological
      activity of the oncoprotein.

PMID- 8547237
TI  - Functional properties of the purified Na(+)-dependent citrate carrier of
      Klebsiella pneumoniae: evidence for asymmetric orientation of the carrier protein
      in proteoliposomes.
AB  - The sodium-ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) was
      purified and reconstituted into liposomes to investigate the properties of this
      transport system without interference from other proteins. Citrate uptake was an
      electroneutral process, where delta pNa+ and/or delta pH are driving forces.
      Delta psi was unable to stimulate citrate transport, either alone or in addition
      to the other driving forces. Sodium ions on the inside of the proteoliposomes
      stimulated the uptake of citrate, indicating that Na+ ions recycle during the
      transport of citrate. CitS also performed Na+ counterflow in the absence of
      citrate. The citrate carrier performed citrate/citrate counterflow but no
      heterologous antiport of citrate with one of the end products arising from the
      anaerobic citrate fermentation pathway (acetate, formate, or bicarbonate) in K.
      pneumoniae. Citrate counterflow kinetics revealed that CitS transports citrate
      according to a simultaneous type of mechanism. The Km and Ki values revealed two
      binding sites for citrate: one with low and one with high affinity. This
      transport mode is in accord with an asymmetric organization of the carrier
      protein in proteoliposomes.

PMID- 8547238
TI  - Potentiation of cationic liposome-mediated gene delivery by polycations.
AB  - We discovered that several high molecular weight cationic polymers, such as
      poly(L-lysine) and protamine, can enhance the transfection efficiency of several
      types of cationic liposomes by 2-28-fold in a number of cell lines in vitro.
      Small polycations such as spermine and a cationic decapeptide derived from SV40 T
      antigen were only moderately active. The addition of poly(L-lysine) and protamine
      dramatically reduced the particle size of the complex formed between DNA and
      cationic liposomes and rendered DNA resistant to the nuclease activity. The
      complexes composed of DNA, poly(L-lysine), and cationic lipids were purified from
      an excess of free liposomes with sucrose gradient ultracentrifugation. Purified
      complex formed at low cationic liposome ratio was poor in lipid content and only
      had weak transfection activity. Addition of free liposome to the purified complex
      significantly enhanced the transfection activity. In contrast, complexes formed
      at a higher initial ratio of liposome to DNA had a higher lipid content and were
      highly active in transfection; the activity was about 3-9-fold more active than
      the corresponding complex before purification. Negative stain EM studies revealed
      that the most active complexes prepared from 40 nmol of lipid, 0.5 micrograms of
      poly(L-lysine), and 1 microgram of DNA and purified by gradient
      ultracentrifugation were spherical, electron dense, small (< 100 nm in diameter)
      particles, and some of them were associated with lipid membranes. These highly
      active, stable, small-sized lipid/poly(L-lysine)/DNA complexes represent a new
      class of nonviral gene delivery vehicles that might be useful in gene therapy.

PMID- 8547239
TI  - Induction of nonbilayer structures in diacylphosphatidylcholine model membranes
      by transmembrane alpha-helical peptides: importance of hydrophobic mismatch and
      proposed role of tryptophans.
AB  - We have investigated the effect of several hydrophobic polypeptides on the phase
      behavior of diacylphosphatidylcholines with different acyl chain length. The
      polypeptides are uncharged and consist of a sequence with variable length of
      alternating leucine and alanine, flanked on both sides by two tryptophans, and
      with the N- and C-termini blocked. First it was demonstrated by circular
      dichroism measurements that these peptides adopt an alpha-helical conformation
      with a transmembrane orientation in bilayers of dimyristoylphosphatidylcholine.
      Subsequent 31P NMR measurements showed that the peptides can affect lipid
      organization depending on the difference in hydrophobic length between the
      peptide and the lipid bilayer in the liquid-crystalline phase. When a 17 amino
      acid residue long peptide (WALP17) was incorporated in a 1/10 molar ratio of
      peptide to lipid, a bilayer was maintained in saturated phospholipids containing
      acyl chains of 12 and 14 C atoms, an isotropic phase was formed at 16 C atoms,
      and an inverted hexagonal (HII) phase at 18 and 20 C atoms. For a 19 amino acid
      residue long peptide (WALP19) similar changes in lipid phase behavior were
      observed, but at acyl chain lengths of 2 C-atoms longer. Also in several cis
      unsaturated phosphatidylcholine model membranes it was found that these peptides
      and a shorter analog (WALP16) induce the formation of nonbilayer structures as a
      consequence of hydrophobic mismatch. It is proposed that this unique ability of
      the peptides to induce nonbilayer structures in phosphatidylcholine model
      membranes is due to the presence of two tryptophans at both sides of the
      membrane/water interface, which prevent the peptide from aggregating when the
      mismatch is increased. Comparison of the hydrophobic length of the bilayers with
      the length of the different peptides showed that it is the precise extent of
      mismatch that determines whether the preferred lipid organization is a bilayer,
      isotropic phase, or HII phase. The peptide-containing bilayer and HII phase were
      further characterized after sucrose density gradient centrifugation of mixtures
      of WALP16 and dioleoylphosphatidylcholine. 31P NMR measurements of the isolated
      fractions showed that a complete separation of both components was obtained.
      Chemical analysis of these fractions in samples with varying peptide
      concentration indicated that the HII phase is highly enriched in peptide
      (peptide/lipid molar ratio of 1/6), while the maximum solubility of the peptide
      in the lipid bilayer is about 1/24 (peptide/lipid, molar). A molecular model of
      the peptide-induced HII phase is presented that is consistent with the results
      obtained thus far.

PMID- 8547240
TI  - Exonucleolytic proofreading during replication of repetitive DNA.
AB  - We are attempting to understand the processes required to accurately replicate
      the repetitive DNA sequences whose instability is associated with several human
      diseases. Here we test the hypothesis that the contribution of exonucleolytic
      proofreading to frameshift fidelity during replication of repetitive DNA
      sequences diminishes as the number of repeats in the sequence increases. The
      error rates of proofreading-proficient T7, T4, and Pyrococcus furiosis DNA
      polymerases are compared to their exonuclease-deficient derivatives, for +1 and 
      1 base errors in homopolymeric repeat sequences of three to eight base pairs. All
      three exonuclease-deficient polymerases produce frameshift errors during
      synthesis at rates that increase as a function of run length, suggesting the
      involvement of misaligned intermediates. Their wild-type counterparts are all
      much more accurate, suggesting that the majority of the intermediates are
      corrected by proofreading. However, the contribution of the exonuclease to
      fidelity decreases substantially as the length of the homopolymeric run
      increases. For example, the exonuclease enhances the frameshift fidelity of T7
      DNA polymerase in a run of three A.T base pairs by 160-fold, similar to its
      contribution to base substitution fidelity. However, in a run of eight
      consecutive A.T base pairs, the exonuclease only enhances frameshift fidelity by
      7-fold. A similar pattern was observed with T4 and Pfu DNA polymerases. Thus,
      both polymerase selectivity and exonucleolytic proofreading efficiency are
      diminished during replication of repetitive sequences. This may place an
      increased relative burden on post-replication repair processes to reduce rates of
      addition and deletion mutations in organisms whose genome contains abundant
      simple repeat DNA sequences.

PMID- 8547241
TI  - HIV-1 reverse transcriptase resistance to nonnucleoside inhibitors.
AB  - The parameters governing the polymerization mechanism of reverse transcriptase
      containing the tyrosine to cysteine mutation at position 181 (Y181C) were
      determined using pre-steady-state techniques. The pathway for single nucleotide
      incorporation catalyzed by Y181C is similar to that determined for wild-type RT
      where a rate-limiting conformational change precedes fast chemistry and is
      followed by slow steady-state release of the primer/template. The Y181C mutant
      enzyme binds a 25/45-mer duplex DNA tightly with a Kd of 11 nM. However, the
      Y181C mutation weakens the nucleotide affinity 2-3-fold relative to the wild-type
      complex. We also determined the parameters governing the mechanism of
      nonnucleoside inhibitor resistance with Y181C. The Kd value of Nevirapine with
      the mutant E.DNA complex increased approximately 500-fold. The decreased affinity
      of Nevirapine for the mutant enzyme is a consequence of a faster inhibitor
      dissociation rate from the enzyme complex of Y181C relative to that of the wild
      type. The E.DNA complex of Y181C may be saturated with Nevirapine, and the
      I.E.DNA complex is capable of a maximum incorporation rate of 0.1 s-1 (a 10-fold
      faster rate than that of the wild-type I.E.DNA complex). The overall two-step
      binding of nucleotide to Y181C in the presence of Nevirapine remains unaffected.

PMID- 8547242
TI  - Dissociation kinetics of echinomycin from CpG binding sites in different sequence
      environments.
AB  - We have examined the kinetics of dissociation of echinomycin from CpG sites in
      several DNA fragments containing synthetic DNA inserts by a variation of the
      footprinting technique. Complexes of the ligand with radiolabeled DNA fragments
      were dissociated by adding an excess of unlabeled calf thymus DNA. Samples were
      removed from this mixture at subsequent time intervals and subjected to DNase I
      footprinting. The rate of disappearance of the footprints varied considerably
      between the various CpG sites. At 20 degrees C, echinomycin dissociates more
      slowly from CpG sites flanked by (AT)n (t1/2 approximately 40 min) and
      (CA)n.(TG)n (t1/2 approximately 11 min) than by An.Tn (t1/2 < 3 min). In each
      sequence context the dissociation from ACGT is slower than that from TCGA.
      (TAA)4CG(TTA)4 also represents a very good binding site (t1/2 approximately 35
      min), which is less sensitive to changes in temperature than most other sites.
      Within sequences (AT)10(G/C)4(AT)10, the dissociation from CGGC is slower than
      that from CCCG or CCGC.

PMID- 8547243
TI  - Substrate binding and turnover by the highly specific I-PpoI endonuclease.
AB  - Intron-encoded endonucleases are distinguished by their ability to catalyze the
      cleavage of double-stranded DNA with high specificity. I-PpoI endonuclease, an
      intron-encoded endonuclease from the slime mold Physarum polycephalum, is a small
      enzyme (2 x 20 kDa) that catalyzes the cleavage of a large asymmetric DNA
      sequence (15 base pairs). Here, the interactions of I-PpoI with its substrate
      were examined during both binding (in the absence of Mg2+) and catalysis (in the
      presence of Mg2+). Using circular permutation assays, I-PpoI was shown to bend
      its substrate by 38 +/- 4 degrees upon binding. Two independent methods, gel
      mobility shift assays and fluorescence polarization assays, revealed that I-PpoI
      binds tightly to its substrate. Values of Kd range from 3.3 to 112 nM, increasing
      with increasing NaCl concentration. Similar salt effects on the values of Km were
      observed during steady-state catalysis. At low salt concentrations, the value of
      kcat/Km for the cleavage of an oligonucleotide duplex approaches 10(8) M-1 s-1.
      Although other divalent cations can replace Mg2+, catalysis by I-PpoI is most
      efficient in the presence of an oxophilic metal ion that prefers an octahedral
      geometry: Mg2+ > Mn2+ > Ca2+ = Co2+ > Ni2+ > Zn2+. Together, these results
      provide the first chemical insight into substrate binding and turnover by an
      intron-encoded endonuclease.

PMID- 8547244
TI  - Dual role of the 44/62 protein as a matchmaker protein and DNA polymerase
      chaperone during assembly of the bacteriophage T4 holoenzyme complex.
AB  - Processive DNA synthesis in the bacteriophage T4 system requires the formation of
      a holoenzyme complex composed of the T4 DNA polymerase and the 44/62 and 45
      accessory proteins. While ATP hydrolysis by the 44/62 protein is essential for
      holoenzyme formation, the role of the sliding clamp or processivity factor is
      attributed to the 45 protein. Beyond the need for ATP hydrolysis, the exact role
      of the 44/62 protein in complex assembly has not been clearly defined. In this
      paper, we have investigated the kinetics of complex assembly in the presence of
      both saturating and substoichiometric concentrations of the 44/62 protein. Under
      saturating conditions, complex assembly is 100% efficient, with all of the
      polymerase bound in a processive complex. Under conditions of limiting 44/62
      protein, the 44/62 protein can act catalytically to assemble the 45 protein and
      polymerase into a productive complex. However, kinetic simulations indicate that
      a significant fraction of polymerase is sequestered in a nonproductive complex
      with the 45 protein. Thus, a second role for the 44/62 protein during complex
      assembly is that of a chaperone protein to ensure productive pol.45.DNA complex
      formation. We have also investigated the stability of the 45 protein on the DNA.
      The off rate of 0.003 s-1 for the 45 protein closely parallels that of the
      holoenzyme complex. Therefore, disassembly of the complex appears to involve the
      coordinated dissociation of both the 45 protein and the polymerase from the DNA.

PMID- 8547245
TI  - Identifying the physiological electron transfer site of cytochrome c peroxidase
      by structure-based engineering.
AB  - A technique was developed to evaluate whether electron transfer (ET) complexes
      formed in solution by the cloned cytochrome c peroxidase [CcP(MI)] and
      cytochromes c from yeast (yCc) and horse (hCc) are structurally similar to those
      seen in the respective crystal structures. Site-directed mutagenesis was used to
      convert the sole Cys of the parent enzyme (Cys 128) to Ala, and a Cys residue was
      introduced at position 193 of CcP(MI), the point of closest contact between
      CcP(MI) and yCc in the crystal structure. Cys 193 was then modified with a bulky
      sulfhydryl reagent, 3-(N-maleimidylpropionyl)-biocytin (MPB), to prevent yCc from
      binding at the site seen in the crystal. The MPB modification has no effect on
      overall enzyme structure but causes 20-100-fold decreases in transient and steady
      state ET reaction rates with yCc. The MPB modification causes only 2-3-fold
      decreases in ET reaction rates with hCc, however. This differential effect is
      predicted by modeling studies based on the crystal structures and indicates that
      solution phase ET complexes closely resemble the crystalline complexes. The low
      rate of catalysis of the MPB-enzyme was constant for yCc in buffers of 20-160 mM
      ionic strength. This indicates that the low affinity complex formed between
      CcP(MI) and yCc at low ionic strength is not reactive in ET.

PMID- 8547246
TI  - Dynamic properties of the minor chlorophyll a/b binding proteins of photosystem
      II, an in vitro model for photoprotective energy dissipation in the
      photosynthetic membrane of green plants.
AB  - Excess light energy absorbed by the chloroplast membranes of green plants is
      dissipated by nonradiative de-excitation in order to protect against photodamage.
      This is observed as the nonphotochemical quenching of chlorophyll fluorescence,
      which has been suggested to result from an alteration in the structure and
      function of the chlorophyll a/b light-harvesting complexes of photosystem II
      (LHCII) due to the combined effects of protonation and the de-epoxidation of
      bound violaxanthin to form zeaxanthin. In agreement with this hypothesis, it is
      shown that the light-harvesting chlorophyll a/b proteins purified from spinach
      leaves exhibit pH-stimulated quenching of chlorophyll fluorescence; this
      quenching shares all the key features observed for the nonphotochemical quenching
      of chlorophyll fluorescence in vivo. In the case of the two minor complexes,
      LHCIIa (CP29) and LHCIIc (CP26), quenching is much greater than in the bulk
      complex LHCIIb and is strongly inhibited by the reagent dicyclohexylcarbodiimide.
      The carotenoids violaxanthin and zeaxanthin cause strong inhibition and
      stimulation of quenching, respectively, in these complexes. The results of this
      study are consistent with the suggestion that the minor light-harvesting
      complexes play a crucial role in photoprotective energy dissipation in the
      photosynthetic membrane of green plants. Moreover, for the first time, a system
      using isolated LHCIIa and LHCIIc for the study of the regulation of light
      harvesting is described.

PMID- 8547247
TI  - 245 GHz high-field EPR study of tyrosine-D zero and tyrosine-Z zero in mutants of
      photosystem II.
AB  - A 245 GHz 8.7 T high-field EPR study of tyrosine-D (TyrD zero) and tyrosine-Z
      (TyrZ zero) radicals of photosystem II (PSII) from Synechocystis PCC 6803 was
      carried out. Identical principal g values for the wild-type Synechocystis and
      spinach TyrD zero showed that the two radicals were in similar electrostatic
      environments. By contrast, the principal g values of the TyrD zero in the D2
      His189Gln mutant of Synechocystis were different from those of the wild-type and
      spinach radicals and were similar to those of the tyrosyl radical in
      ribonucleotide reductase. These comparisons indicate that the D2-His189Gln mutant
      TyrD zero is not hydrogen-bonded or is only weakly so. The HF-EPR spectrum of
      TyrZ zero was obtained from the D2-Tyr160Phe mutant that lacks TyrD zero. The
      principal g values were nearly identical to those of the wild-type TyrD zero. The
      low-field edge of the TyrZ zero spectrum was much broader than at the other two
      principal g values and was also much broader than the TyrD zero spectrum. From
      the identical g values and previous work on tyrosyl radical g values [Un S., Atta
      M., Fontecave, M., & Rutherford, A. W. (1995) J. Am. Chem. Soc. 117, 10713
      10719], it was concluded that TyrZ zero, like TyrD zero, is hydrogen-bonded The
      broadness of the gx component was interpreted as a distribution in strength of
      the hydrogen-bonding due to disorder in the protein environment about TyrZ zero.

PMID- 8547248
TI  - Binding of the neurotoxin fasciculin 2 to the acetylcholinesterase peripheral
      site drastically reduces the association and dissociation rate constants for N
      methylacridinium binding to the active site.
AB  - The acetylcholinesterase (AChE) active site consists of a gorge 2 nm deep that is
      lined with aromatic residues. A serine residue near the base of the gorge defines
      an acylation site where an acyl enzyme intermediate is formed during the
      hydrolysis of ester substrates. Residues near the entrance to the gorge comprise
      a peripheral site where inhibitors like propidium and fasciculin 2, a snake
      neurotoxin, bind and interfere with catalysis. Like certain other cationic
      ligands that bind specifically to the acylation site, N-methylacridinium can
      still interact with the acylation site in the AChE-fasciculin 2 complex. At 310 K
      (37 degrees C), the equilibrium dissociation constant KL' for N-methylacridinium
      binding to the complex was 4.0 +/- 0.7 microM, less than an order of magnitude
      larger than the KL = 1.0 +/- 0.3 microM for N-methylacridinium interaction with
      human AChE in the absence of fasciculin 2. To assess whether fasciculin 2 can
      sterically block access of a ligand to the acylation site, thermodynamic and
      kinetic constants for the interaction of N-methylacridinium with AChE in the
      presence and absence of fasciculin 2 were measured by fluorescence temperature
      jump relaxation kinetics. During progressive titration of the enzyme with
      increasing concentrations of N-methylacridinium, a prominent relaxation in the
      0.1-1 ms range was observed in the absence of fasciculin 2. When excess
      fasciculin 2 was added, the prominent relaxation shifted to the 0.3-1 s range.
      Estimates of total AChE concentrations, KL, or KL' from analyses of relaxation
      amplitudes agreed well with those from equilibrium fluorescence, confirming that
      the relaxations corresponded to the bimolecular reactions of interest. Further
      analysis of the relaxation times in the absence of fasciculin 2 gave estimates of
      the N-methylacridinium association rate constant k12 = 8 x 10(8) M-1 s-1 and
      dissociation rate constant k21 = 750 s-1 at 310 K (37 degrees C). For the AChE
      fasciculin 2 complex, the corresponding constants were k12' = 1.0 x 10(5) M-1 s-1
      and k21' = 0.4 s-1. Thus the rate constants decreased by more than 3 orders of
      magnitude when fasciculin 2 was bound, consistent with a pronounced steric
      blockade of N-methylacridinium ingress to and egress from the acylation site.

PMID- 8547249
TI  - Fast events in protein folding: helix melting and formation in a small peptide.
AB  - The helix is a common secondary structural motif found in proteins, and the
      mechanism of helix-coil interconversion is key to understanding the protein
      folding problem. We report the observation of the fast kinetics (nanosecond to
      millisecond) of helix melting in a small 21-residue alanine-based peptide. The
      unfolding reaction is initiated using a laser-induced temperature jump and probed
      using time-resolved infrared spectroscopy. The model peptide exhibits fast
      unfolding kinetics with a time constant of 160 +/- 60 ns at 28 degrees C in
      response to a laser-induced temperature jump of 18 degrees C which is completed
      within 20 ns. Using the unfolding time and the measured helix-coil equilibrium
      constant of the model peptide, a folding rate constant of approximately 6 x 10(7)
      s-1 (t1/2 = 16 ns) can be inferred for the helix formation reaction at 28 degrees
      C. These results demonstrate that secondary structure formation is fast enough to
      be a key event at early times in the protein-folding process and that helices are
      capable of forming before long range tertiary contacts are made.

PMID- 8547250
TI  - Proline pipe helix: structure of the tus proline repeat determined by 1H NMR.
AB  - The structure of a 22 amino acid peptide, TPPI [Nedved, M. L., Gottlieb, P. A., &
      Moe, G. R. (1994) Nucleic Acids Res. 22, 5024-5030], that is similar to the
      proline repeat segment of the replication arrest protein, Tus, has been
      determined by 1H NMR in 50% trifluroethanol. The structure is a novel left-handed
      helix having 5.56 residues per turn and a regular hydrogen bonding network that
      is limited to one side of the helix and contains a channel that runs down the
      helix axis. The latter feature gives the structure an overall pipe-like
      appearance; hence, the structure has been designated a proline pipe helix. The
      Tus proline pipe is also amphiphilic with one side consisting of proline and
      other nonpolar residues while the other side contains mostly basic and other
      polar residues. Tus and several other proteins that contain a similar proline
      repeat sequence are DNA binding proteins. It is shown here that the proline pipe
      helix of TPPI can be accommodated within the major grove of B-form DNA in a
      manner that positions nearly all of the basic residues near phosphate groups in
      the DNA backbone. The proline pipe helical motif may be a structural element of
      many other proteins including integral membrane receptor proteins.

PMID- 8547251
TI  - Transformation of cooperative free energies between ligation systems of
      hemoglobin: resolution of the carbon monoxide binding intermediates.
AB  - A strategy has been developed for quantitatively "translating" the distributions
      of cooperative free energy between different oxygenation analogs of hemoglobin
      (Hb). The method was used to resolve the cooperative free energies of all eight
      carbon monoxide binding intermediates. These parameters of the FeCOHb system were
      determined by thermodynamic transformation of corresponding free energies
      obtained previously for all species of the Co/FeCO system, i.e., where cobalt
      substituted hemes comprise the unligated sites [Speros, P. C., et al. (1991)
      Biochemistry 30, 7254-7262]. Using hybridized combinations of normal and cobalt
      substituted Hb, ligation analog systems Co/FeX (X = CO, CN) were constructed and
      experimentally quantified. Energetics of cobalt-induced structural perturbation
      were determined for all species of both the "mixed metal" Co/Fe system and also
      the ligated Co/FeCN system. It was found that major energetic perturbations of
      the Co/Fe hybrid species originate from a pure cobalt substitution effect on the
      alpha subunits. These perturbations are transduced to the beta subunit within the
      same dimeric half-tetramer, resulting in alteration of the free energies for
      binding at the nonsubstituted (Fe) sites. Using the linkage strategy developed in
      this study along with the determined energetics of these couplings, the
      experimental assembly free energies for the Co/FeCO species were transformed into
      cooperative free energies of the 10 Fe/FeCO species. The resulting values were
      found to distribute according to predictions of a symmetry rule mechanism
      proposed previously [Ackers, G. K., et al. (1992) Science 255, 54-63]. Their
      distribution is consistent with accurate CO binding data of normal Hb [Perrella,
      M., et al. (1990b) Biophys. Chem. 37, 211-223] and also with accurate O2 binding
      data obtained under the same conditions [Chu, A. H., et al. (1984) Biochemistry
      23, 604-617].

PMID- 8547252
TI  - Effect of adenine methylation on the structure and dynamics of TpA steps in DNA:
      NMR structure determination of [d(CGAGGTTTAAACCTCG)]2 and its A9-methylated
      derivative at 750 MHz.
AB  - At TpA steps in DNA, the adenine base experiences exceptionally large amplitude
      (20 degrees-50 degrees) and slow (10 ms-1 microsecond) motion [Kennedy et al.
      (1993) Biochemistry 32, 8022-8035] which has been correlated with transitions
      between multiple conformational states [Lefevre et al. (1985) FEBS Lett. 190, 37
      40]. The base dynamics can be detected in one-dimensional 1H NMR spectra as
      excess line width of the aromatic proton resonances. The magnitude of the excess
      line width is temperature dependent and reaches a maximum at some temperature. In
      order to better understand the origin of the dynamics, we have studied the effect
      of N6-methylation of the TpA adenine on both the line widths and its local
      structure. Here, solution-state 500 and 750 MHz 1H NMR data collected on
      [d(CGAGGTTTAAACCTCG)]2 show that the excess line width of the TpA adenine-H2 is
      diminished when the TpA adenine is N6-methylated and that the line width no
      longer experiences a maximum as the temperature is varied. The resonances sharpen
      upon methylation because the amplitude of base motion is restricted due to steric
      effects and due to other structural changes at the TpA site. Additionally, both
      the TpA adenine-H8 and the exchangeable imino resonance of thymine at the TpA
      step were also found to have excess line width that is diminished upon N6
      methylation. In order to elucidate the structural features responsible for TpA
      base dynamics, solution-state NMR structures of [d(CGAGGTTTAAACCTCG)]2 and its A9
      N6-methylated derivative were determined at 750 MHz. Comparison of the structures
      shows that poor base stacking at the TpA step may contribute to, or be the origin
      of, its base dynamics.

PMID- 8547253
TI  - High-resolution structure of an engineered Cro monomer shows changes in
      conformation relative to the native dimer.
AB  - A rationally designed, genetically engineered, monomeric form of the Cro protein
      from bacteriophage lambda has been crystallized and its structure determined by
      isomorphous replacement and refined to a resolution of 1.54 A. The structure
      confirms the rationale of the design but, at the same time, reveals 1-2 A shifts
      throughout the monomer structure relative to the previously determined structure
      of the dimeric wild-type protein. These changes include a 1.6 A main-chain shift
      in part of the beta-sheet region of the molecule relative to the alpha-helical
      region and a 1.1 A shift of a buried phenylalanine within the core as well as a
      correlated 2.2 A shift in a solvent-exposed beta-hairpin. The conformational
      adjustments appear to reflect an inherent flexibility of the protein that is
      associated with its DNA-binding function.

PMID- 8547254
TI  - Core packing defects in an engineered Cro monomer corrected by combinatorial
      mutagenesis.
AB  - The crystal structure of an engineered monomer of the lambda Cro repressor shows
      unexpected expansion of the hydrophobic core of the protein and disorder of the
      five C-terminal residues [Albright et al. (1996) Biochemistry 35, 735-742]. This
      structural information has guided the construction of a second generation of
      monomeric Cro proteins by combinatorial mutagenesis of selected core and C
      terminal residues. Clones were identified in a library of randomized cro genes by
      a genetic screen for protein accumulation in Escherichia coli. Sequencing of
      candidate genes followed by purification and analysis of their product proteins
      has identified alternative arrangements of hydrophobic core residues which result
      in substantial increases in thermal stability. In contrast, residue replacements
      at the C-terminus have minor effects on stability but may increase protein
      expression levels.

PMID- 8547255
TI  - In vitro growth of Alzheimer's disease beta-amyloid plaques displays first-order
      kinetics.
AB  - A salient pathological feature of Alzheimer's disease (AD) is the presence of
      amyloid plaques in the brains of affected patients. The plaques are predominantly
      composed of human beta-amyloid peptide (A beta). Although the aggregation of
      synthetic A beta has been extensively studied, the mechanism of AD plaque growth
      is poorly understood. In order to address this question, we used an in vitro
      model of plaque growth to determine if assembly or aggregation of A beta is
      required for deposition. Labeled A beta at physiological concentrations readily
      deposited onto both neuritic and diffuse plaques and cerebrovascular amyloid in
      unfixed AD brain tissue, whereas essentially no deposition was detected in tissue
      without performed amyloid. Using this in vitro model of plaque growth, the
      kinetics of A beta deposition onto plaques was examined in two independent but
      complementary systems. Intact sections of unfixed AD brain cortex (analyzed by
      autoradiographic densitometry) allowed definitive morphological analysis of the
      site of deposition, while homogenates of the same tissue (analyzed by
      radioisotope counting) allowed precise quantitation of deposition over a wide
      range of conditions. Essentially identical results were obtained for both
      systems. Growth of preexisting tissue plaques by deposition of A beta was found
      to follow first-order dependence on A beta concentration and exhibited a pH
      optimum of 7. In sharp contrast, A beta aggregation in the absence of template
      follows higher order kinetics and shows a pH optimum of 5. On the basis of
      criteria of kinetic order, pH dependence, and structure-activity relationships,
      we conclude that aggregation of A beta (template-independent initial nidus
      formation) and deposition of A beta (template-dependent subsequent plaque growth)
      are fundamentally distinct biochemical processes. The process of plaque growth
      and maturation by A beta deposition may be an important target for therapeutic
      intervention to block the progression of AD.

PMID- 8547256
TI  - Monosialogangliosides of human myelogenous leukemia HL60 cells and normal human
      leukocytes. 1. Separation of E-selectin binding from nonbinding gangliosides, and
      absence of sialosyl-Le(x) having tetraosyl to octaosyl core.
AB  - Previous studies suggested that sialosyl-Le(x) (SLex) is a ligand expressed in
      human neutrophils and myelogenous leukemia HL60 cells which binds to E-selectin
      and possibly P-selectin. However, clear data on structures of carbohydrate
      epitopes in these cells were lacking. A systematic study was therefore initiated,
      employing a large quantity of HL60 cells (> or = 1200 mL packed) and human
      leukocytes (approximately 100 mL packed). Gangliosides were extracted, followed
      by extensive fractionation and examination of the E- and P-selectin binding
      ability of each fraction. The following results were of particular interest: (i)
      Only monosialogangliosides having a polylactosamine core with > 10 monosaccharide
      units (or > 4 N-acetyllactosamine units) showed E-selectin binding under static
      conditions with thin-layer chromatography overlay technique employing 32P-labeled
      E-selectin-expressing CHO cells. (ii) Sulfate groups were not detectable in the
      binding fractions, and di- and trisialoganglioside fractions did not show E
      selectin binding under these conditions. (iii) None of the fractions showed P
      selectin binding under a similar assay system using 32P-labeled P-selectin
      expressing CHO cells. (iv) Major gangliosides of HL60 cells were structures I-XI
      (shown in Table 1 of text), none of which showed E-selectin binding under the
      above conditions. (v) SLex gangliosides having tetraosyl to octaosyl ceramide
      core, which are the major gangliosides of epithelial tumors (shown in Table 2),
      were completely absent from HL60 cells and neutrophils. Isolation and chemical
      characterization of ganglioside structures I-XI are described in this paper.

PMID- 8547257
TI  - Monosialogangliosides of human myelogenous leukemia HL60 cells and normal human
      leukocytes. 2. Characterization of E-selectin binding fractions, and structural
      requirements for physiological binding to E-selectin.
AB  - E-selectin binding gangliosides were isolated from myelogenous leukemia HL60
      cells, and the E-selectin binding pattern was compared with that of human
      neutrophils as described in the preceding paper in this issue. The binding
      fractions were identified as monosialogangliosides having a series of unbranched
      polylactosamine cores. Structures of fractions 12-3, 13-1, 13-2, and 14, which
      showed clear binding to E-selectin under the conditions described in the
      preceding paper, were characterized by functional group analysis by application
      of monoclonal antibodies, 1H-NMR, FAB-MS, and electrospray mass spectrometry with
      collision-induced dissociation of permethylated fractions. Fractions 12-3, 13-1,
      and 13-2 were characterized by the presence of a major ganglioside with the
      following structure: NeuAc alpha 2-->3Gal beta 1-->4 GlcNAc beta 1-->3Gal beta 1-
      >4(Fuc alpha 1-->3) GlcNAc beta 1-->3Gal beta 1-->4(Fuc alpha 1-->3)-GlcNAc beta
      1-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1-->4 Glc beta Cer. Fractions 12-3
      and 13-2 contained, in addition, small quantities (10-15%) of extended SLex with
      internally fucosylated structures: NeuAc alpha 2-->3 Gal beta 1-->4-(Fuc alpha 1-
      >3) GlcNAc beta 1-->3 Gal beta 1-->4(Fuc alpha 1-->3) GlcNAc beta 1-->3 Gal beta
      1-->4 (+/- Fuc alpha 1-->3)GlcNA c beta 1-->3 Gal beta beta 1-->4GlcNAc beta 1-
      >3 Gal beta 1-->Glc Beta Cer. Fraction 13-1, showing stronger E-selectin binding
      activity than 12-3 and 13-2, contained only a trace quantity (< 1%) of SLex.
      Fraction 14, which also showed clear binding to E-selectin, was characterized by
      the presence of the following structures, in addition to two internally
      monofucosylated structures (XX and XXI, Table 2, text): NeuAc alpha 2-->3Gal beta
      1-->4GlcNAc beta 1-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3 Gal beta 1
      ->4(Fuc alpha 1-->3)GlcNAc beta 1-->3Gal beta 1-->4 GlcNAc beta 1-->3 Gal beta 1-
      >4 GlcNAc beta 1-->3 Gal beta 1-->4 Glc beta Cer; andNeuAc alpha 2-->3Gal beta 1-
      >4GlcNAc beta 1-->3 Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc beta 1-->3Gal beta 1-
      >4GlcNAc beta 1-->3Gal beta 1-->4 (Fuc alpha 1--3)-GlcNAc beta 1-->3Gal beta 1-
      >4GlcNAc beta 1-->3Gal beta 1--4Glc beta Cer. SLex determinant was completely
      absent. Thus, the E-selectin binding epitope in HL60 cells is carried by
      unbranched terminally alpha 2-->3 sialylated polylactosamine having at least 10
      monosaccharide units (4 N-acetyllactosamine units) with internal multiple
      fucosylation at GlcNAc. These structures are hereby collectively called
      "myeloglycan". Monosialogangliosides from normal human neutrophils showed an
      essentially identical pattern of gangliosides with selectin binding property.
      Myeloglycan, rather than SLex, provides a major physiological epitope in E
      selectin-dependent binding of leukocytes and HL60 cells.

PMID- 8547258
TI  - Amide hydrogen exchange determined by mass spectrometry: application to rabbit
      muscle aldolase.
AB  - The protein fragmentation/mass spectrometry method described by Zhang and Smith
      [(1993) Protein Sci. 2, 522-531] has been extended to measure amide hydrogen
      exchange rates in rabbit muscle aldolase, a homotetramer with M(r) = 157,000.
      Following a period of deuterium exchange, the partially deuterated protein was
      proteolytically fragmented into peptides whose deuterium contents were determined
      by directly coupled HPLC fast atom bombardment mass spectrometry. Hydrogen
      exchange rates were determined for amide hydrogens located in short segments
      derived from 85% of the aldolase backbone. Isotopic exchange rate constants
      spanning the range from 100 to 0.001 h-1 were determined for the exchange-in
      times used in this study (2.5 min to 44 h). The exchange rates for amide
      hydrogens located within short segments differed by as much as 10(4),
      demonstrating that local structural features dramatically affect the isotopic
      exchange rates in large proteins. A high level of correlation between the slowing
      of hydrogen exchange and intramolecular hydrogen bonding in aldolase was found.
      An exception to this correlation occurs at the subunit interface, where the amide
      hydrogens in one peptide segment with few amide hydrogen bonds have slower
      exchange rates than expected, suggesting that the amide hydrogens in this region
      are effectively shielded from the deuterated solvent. Isotope patterns observed
      for most peptides were binomial, indicating that hydrogen exchange proceeds
      through the EX2 mechanism (uncorrelated exchange). However, bimodal isotope
      patterns were found for peptides derived from three short segments of aldolase
      (including residues 58-64, 279-283, and 326-337), suggesting structural
      differences in these regions. A high level of correlation was found between
      crystallographic B-factors and amide hydrogen exchange rates, suggesting an
      isotopic exchange mechanism involving localized low-amplitude, high-frequency
      motions that do not require collective motion of many residues. From a
      methodology viewpoint, these results demonstrate that the combination of protein
      fragmentation with mass spectrometry is a useful method for determining the rates
      at which amide hydrogens located over major portions of large proteins undergo
      isotopic exchange.

PMID- 8547259
TI  - Enzymatic ketonization of 2-hydroxymuconate: specificity and mechanism
      investigated by the crystal structures of two isomerases.
AB  - 5-Carboxymethyl-2-hydroxymuconate isomerase (CHMI) and 4-oxalocrotonate
      tautomerase (4-OT) are enzymes that catalyze the isomerization of unsaturated
      ketones. They share a common enzyme mechanism, although they show a preference
      for different substrates. There is no apparent sequence homology between the
      enzymes. To investigate the molecular mechanism and the basis for their substrate
      specificity, we have determined the crystal structures of the two enzymes at high
      resolution. 4-OT is hexameric, with the subunits arranged with 32 symmetry. CHMI
      is trimeric and has extensive contacts between subunits, which include secondary
      structural elements. The central core of the CHMI monomer has a fold similar to a
      4-OT dimer, but the secondary structural elements that form the subunit contacts
      around the 3-fold axis are different in the two enzymes. The region of greatest
      similarity between the two enzymes is a large pocket that is proposed to be the
      active site. The enzymes appear to operate via a "one-base" mechanism, and the
      possible role of residues in this pocket is discussed in view of this idea.
      Finally, the molecular basis for substrate specificity in the two enzymes is
      discussed.

PMID- 8547260
TI  - Catalytic role of the amino-terminal proline in 4-oxalocrotonate tautomerase:
      affinity labeling and heteronuclear NMR studies.
AB  - 4-Oxalocrotonate tautomerase (EC 5.3.2-; 4-OT), a hexamer consisting of 62
      residues per subunit, catalyzes the isomerization of unsaturated alpha-keto
      acids, converting unconjugated ketones to the conjugated isomers via a dienolic
      intermediate. The recently solved crystal structure of an isozyme of 4-OT
      suggests that the amino-terminal proline is the catalytic base [Subramanya, H.
      S., Roper, D. I., Dauter, Z., Dodson, E. J., Davies, G. J., Wilson, K. S., &
      Wigley, D. B. (1996) Biochemistry 35, 792-802]. In support of this proposed role,
      we have found that the active-site-directed irreversible inhibitor 3
      bromopyruvate (3-BP) blocks the amino terminus of 4-OT to Edman degradation and
      results in the disappearance of the 15N resonance of Pro-1 (delta = 49.2 ppm at
      pH 6.40 and 42 degrees C) in the 15N NMR spectrum of uniformly 15N-labeled 4-OT.
      Furthermore, covalent bonding between a 15N resonance of 4-OT and the methylene
      carbon of the reduced, 3-(13)C-labeled lactyl adduct derived from [3-(13)C]
      bromopyruvate was then directly demonstrated using two heteronuclear NMR methods,
      an 1H-(13)C HSQC experiment and a novel inverse correlation experiment which we
      call H(C)N. The chemical shift of the modified 15N resonance (delta = 86.5 ppm)
      is consistent with that of an alkylated and cationic, amino-terminal proline.
      Affinity labeling with 2-(14)C-labeled bromopyruvate indicates that the ultimate
      stoichiometry of modification is I equiv of 3-BP per 4-OT monomer. However, an
      analysis of the residual enzyme activity after differing extents of fractional
      modification with 3-BP indicates that modification of three active sites per
      hexamer abolishes essentially all activity of the hexamer. Thus, 4-OT exhibits
      half-of-the-sites stoichiometry with 3-BP. Finally, the pH dependence of
      kinact/KI for affinity labeling by 3-BP yields a pKa value of 6.7 +/- 0.3, in
      reasonable agreement with the pKa values found for kcat/KM for the non-sticky
      substrate 2-hydroxy-2,4-pentadienoate and by direct NMR titration of Pro-1
      [Stivers, J. T., Abeygunawardana, C., Mildvan, A. S., Hajipour, G., & Whitman, C.
      P. (1996) Biochemistry 35, 814-823]. These results strongly implicate the amino
      terminal proline as the general-base catalyst on 4-OT.

PMID- 8547261
TI  - 4-Oxalocrotonate tautomerase: pH dependence of catalysis and pKa values of active
      site residues.
AB  - The pH-rate profiles for the kinetic parameters of 4-oxalocrotonate tautomerase
      (4-OT) have been measured using 2-hydroxy-2,4-hexadiendioate (2a) and 2-hydroxy
      2,4-pentadienoate (2b) as substrates. The pH dependences of log (kcat/Km) and of
      log kcat for the slow, nonsticky substrate 2b, which lacks a 6-carboxyl group,
      were bell-shaped with limiting slopes of unity on both sides of the pH optimum.
      For 2b, pKa values of 6.2 +/- 0.3 and 9.0 +/- 0.3 for the free enzyme (pKE) and
      7.7 +/- 0.3 and 8.5 +/- 0.3 for the ES complex (pKES) were obtained. The pKE of
      6.2 +/- 0.3 for 2b represents a true pKa for a basic group on the enzyme and is
      most likely Pro-1 on the basis of inhibition studies with the substrate-based
      affinity label 3-bromopyruvate (3-BP) [Stivers et al. (1996) Biochemistry 35, 803
      813]. Accordingly, 15N NMR titration of the uniformly 15N-labeled enzyme showed
      that the pKa of the amino group of Pro-1 is 6.4 +/- 0.2, in reasonable agreement
      with those found by the effect of pH on kcat/Km for 2b (6.2 +/- 0.3) and on
      kinact/K1 for 3-BP (6.7 +/- 0.3), but three units lower than the pKa of the model
      compound proline amide (pKa = 9.4 +/- 0.2). The pKa values for the two histidine
      residues of 4-OT, which were measured by 1H NMR (His-6, pKa < or = 5; His-49, pKa
      = 5.2 +/- 0.2), are at least one pK unit lower than the pKE, excluding these
      residues as candidates for the general base. A plot of log (kcat/Km) vs pH for
      the 10(4)-fold more reactive, but sticky substrate 2a [(kcat/Km)max = 3.9 x 10(6)
      M-1 s-1] shows a limiting slope of two on the ascending limb indicating the
      ionization of two essential groups on the free enzyme and/or substrate. One of
      these groups, with a pKa value of 5.4, is reasonably assigned to the 6
      carboxylate moiety of 2a (pKaCOOH = 5.4). This assignment is supported by the
      slope of unity for the ascending limb of log (kcat/Km) versus pH for 2b which
      lacks this group. Thus a negative charge at the 6-position is important for
      substrate binding and catalysis. The other group (pKa2 = 5.2) most likely
      represents a perturbed pKa for the general base Pro-1 (pKatrue = 6.4). The
      descending limb of log kcat/Km vs pH for 2a has a slope of unity and was fit to a
      single pKa3 = 10.3 +/- 0.2. The pH dependence of kcat for 2a gives pKa values for
      the ES complex (pKES) of 6.5 and 9.6. On the basis of these results, an
      isomerization mechanism involving general-base catalysis by a low pKa proline-1
      and electrophilic catalysis by an as yet unidentified enzymic general-acid (pKa =
      9.0) is proposed.

PMID- 8547263
TI  - Analysis of the absorption spectrum of photosystem II reaction centers:
      temperature dependence, pigment assignment, and inhomogeneous broadening.
AB  - In this study a model for decomposition and pigment assignment of the low
      temperature (10 K) absorption spectrum of the photosystem II reaction center (D1
      D2-cytochrome b559 complex, PSII-RC) is developed. It is based on theoretical
      calculations of the line shapes of the inhomogeneously broadened pigment spectra,
      taking into account electron-phonon coupling. The analysis is performed under the
      hypothesis that exciton coupling is weak, except for the P680 special pair. In
      this way a detailed decomposition of the absorption spectrum is obtained. Within
      the model the temperature dependence of the spectrum can be well explained. It is
      mainly caused by the temperature-dependent changes of the homogeneous absorption
      spectra of the individual pigments in the PSII-RC. In addition, slight changes in
      the inhomogeneous distribution functions have to be taken into account. Two
      slightly different parameter sets are found. We prefer one of these parameter
      sets which indicates that an accessory chlorophyll (Chl) is the lowest energy
      pigment in the RC core and that the two antenna Chls have their spectral maxima
      at 667.7 and 677.9 nm, respectively. The relationship between the shape of the
      absorption spectrum and the pigment stoichiometry of the sample (ratio of
      chlorophyll a:pheophytin a), which was noticed by comparison of a variety of
      different independently prepared samples, can be explained by the presence of
      "additional" Chl molecules which are nonstoichiometrically bound to part of the
      PSII-RCs. These Chls can be grouped into three spectrally distinguishable pools.
      One of them has its absorption maximum at about 683 nm and is responsible for the
      prominent shoulder that is present in the 10 K absorption spectra of most PSII-RC
      preparations. Our results suggest that the Chl content of the samples has been
      underestimated in many spectroscopic studies on the PSII-RC.

PMID- 8547264
TI  - Mechanism of native oat phytochrome photoreversion: a time-resolved absorption
      investigation.
AB  - The regulation of plant photomorphogenesis is mediated by the thermal reactions
      that follow light absorption by the phytochrome photoreceptor. Phytochromes are
      tetrapyrrolic chromoproteins that exist in two photochromically interconvertible
      forms, a red light absorbing species, Pr, and a far-red light absorbing form,
      Pfr. Upon irradiation with 670 nm light, the inactive, red light sensing Pr form
      is converted to the active Pfr form. Although the forward phototransformation has
      been studied extensively by several groups using various techniques, the Pfr-->Pr
      photoreversion reaction that occurs upon irradiation with 730 nm light is not as
      thoroughly characterized. In this study, time-resolved absorption (TROD)
      spectroscopy is used to examine the intermediate species involved in the
      phytochrome photoreversion mechanism at 10 degrees C. Analysis of the TROD data
      identifies three species with lifetimes of 320 ns, 265 microseconds, and 5.5 ms.
      TROD results are described in terms of the simplest parallel and sequential
      kinetic models. Comparison of intermediate spectra from these mechanisms with
      those of previously reported species from flash photoreversion and low
      temperature studies indicates that Pfr photoreversion follows a sequential
      pathway that does not share any intermediates with the Pr phototransformation
      pathway.

PMID- 8547262
TI  - A ligand-exchange mechanism of proton pumping involving tyrosine-422 of subunit I
      of cytochrome oxidase is ruled out.
AB  - The molecular mechanism by which proton pumping is coupled to electron transfer
      in cytochrome c oxidase has not yet been determined. However, several models of
      this process have been proposed which are based on changes occurring in the
      vicinity of the redox centers of the enzyme. Recently, a model was described in
      which a well-conserved tyrosine residue in subunit I (Y422) was proposed to
      undergo ligand exchange with the histidine ligand (H419) of the high-spin heme a3
      during the catalytic cycle, allowing both residues to serve as part of a proton
      transporting system. Site-directed mutants of Y422 have been constructed in the
      aa3-type cytochrome c oxidase of Rhodobacter sphaeroides to test this hypothesis
      (Y422A, Y422F). The results demonstrate that Y422 is not an essential residue in
      the electron transfer and proton pumping mechanisms of cytochrome c oxidase.
      However, the results support the predicted proximity of Y422 to heme a3, as now
      confirmed by crystal structure. In addition, it is shown that the pH-dependent
      reversed electron transfer between heme a and heme a3 is normal in the Y422F
      mutant. Hence, these data also demonstrate that Y422 is not the residue
      previously postulated to interact electrostatically with heme a3, nor is it
      responsible for the unique EPR characteristics of heme a in this bacterial
      oxidase.

PMID- 8547265
TI  - 2H NMR detection of transmembrane potential-driven tetraphenylphosphonium
      transbilayer redistribution.
AB  - 2H NMR of specifically choline-deuterated phosphatidylcholine incorporated into
      giant unilamellar vesicles (GUVs), composed of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) plus 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol
      (POPG) plus cholesterol (CHOL), was shown to detect a transmembrane potential
      driven redistribution of the potential-sensitive, surface- binding dye
      tetraphenylphosphonium (TPP+) across the GUV lipid bilayer. The method is based
      on resolving differences in the surface charge at the inner versus the outer
      monolayer of the vesicle's bilayer using the so-called 2H NMR "molecular
      voltmeter" technique. A mathematical model to describe the 2H NMR results was
      derived by combining the Nernst, Boltzmann, Langmuir, and Gouy-Chapman equations
      with the established sensitivity of deuterium quadrupolar splittings from choline
      deuterated POPC to surface electrostatic charge effects. This model identified
      experimental factors likely to yield enhanced sensitivity and resolution of the
      inner versus outer monolayer surface charges via 2H NMR. The predictions of the
      model were then confirmed experimentally. The improvement in resolution resulting
      from these studies removes a major hindrance to the general exploitation of 2H
      NMR for monitoring transbilayer surface charge asymmetrics.

PMID- 8547266
TI  - Disulfide determinants of calcium-induced packing in alpha-lactalbumin.
AB  - alpha-Lactalbumin (alpha-LA) is a two-domain calcium-binding protein that folds
      through a molten globule intermediate. Calcium binding to the wild-type alpha-LA
      molten globule induces a transition to the native state. Here we assess the
      calcium-binding properties of the alpha-LA molten globule by studying two
      variants of alpha-LA. alpha-LA(alpha) contains only the two disulfide bonds in
      the alpha-helical domain of alpha-LA, while alpha-LA(beta) contains only the beta
      sheet domain and interdomain disulfide bonds. We found that only alpha-LA(beta)
      binds calcium, leading to the cooperative formation of substantial tertiary
      interactions. In addition, the beta-sheet domain acquires a native-like backbone
      topology. Thus, specific interactions within alpha-LA imposed by the beta-sheet
      domain and interdomain disulfide bonds, as opposed to the two alpha-helical
      domain disulfides, are necessary for the calcium-induced progression from the
      molten globule toward more native-like structure. Our results suggest that
      organization of the beta-sheet domain, coupled with calcium binding, comprises
      the locking step in the folding of alpha-LA from the molten globule to the native
      state.

PMID- 8547267
TI  - Thermodynamic role of the pro region of the neurophysin precursor in neurophysin
      folding: evidence from the effects of ligand peptides on folding.
AB  - Attention has focused recently on the role of amino-terminal precursor pro
      regions in protein folding, with particular emphasis on their effects on folding
      kinetics. We examined the kinetic and thermodynamic effects of ligand peptides on
      the folding of neurophysin from the reduced state; these peptides serve as
      analogs of the pro regions of the common precursors of the neurophysins and the
      hormones oxytocin and vasopressin. Folding of reduced, mononitrated bovine
      neurophysin-II was monitored by circular dichroism in a glutathione redox buffer.
      The results confirmed the ability of neurophysin to fold to a limited extent (20
      25% in this system) in the absence of ligand peptides. Ligand peptides increased
      the efficiency of folding to 100%, the exact efficiency being dependent on
      peptide identity and concentration. However, the rate of folding was peptide
      independent. Analysis of the folding reaction demonstrated relatively rapid
      conversion of the reduced state to a disulfide-scrambled state, which slowly
      converted (half-life of 5 h at pH 7.3) to the folded state. Native unliganded
      neurophysin also equilibrated with the disulfide-scrambled state in the same
      redox buffers. For each peptide, an equilibrium constant for the folding
      reaction, representing the amount of peptide bound in the folding system as a
      function of peptide concentration, was calculated. Comparison of this constant
      with the intrinsic binding constants of the native protein allowed the
      derivation, under conditions at or approaching thermodynamic reversibility, of
      the relative stability of the native and disulfide-scrambled states. The results
      indicate that the scrambled state, which probably represents the presence of
      incorrect disulfide pairs in both protein domains, is more stable than the native
      unliganded state by approximately 1 kcal/mol in this system. The role of ligand
      peptide therefore is to stabilize the folded protein after it is formed, i.e., it
      provides a thermodynamic sink. The results contrast with the putative behavior of
      exogenous peptides representative of the pro regions of subtilisin and alpha
      lytic protease, which are generally considered to facilitate folding by reaction
      with folding intermediates. A potential alternative view of the role of
      propeptides in protease folding is suggested.

PMID- 8547268
TI  - The manganese stabilizing protein of photosystem II modifies the in vivo
      deactivation and photoactivation kinetics of the H2O oxidation complex in
      Synechocystis sp. PCC6803.
AB  - Dark deactivation and photoactivation of H2O-splitting activity were examined in
      a directed mutant (delta psbO) of Synechocystis sp. PCC6803 lacking the extrinsic
      manganese-stabilizing protein of the photosystem II (PSII) reaction center
      complex. Rapid (t1/2 = 10 min) losses of H2O-splitting activity were observed for
      delta psbO cells kept in the dark, but not for wild-type cells. The loss of H2O
      splitting activity by delta psbO cells was suppressed by maintaining the cells
      under illumination and dark losses were rapidly (t1/2 < 1 min) reversed by light.
      Photoactivation kinetics of delta psbO and wild-type cells were compared
      following hydroxylamine extraction of PSII Mn. Photoactivation of delta psbO
      cells under continuous illumination occurs at an intrinsically faster rate (about
      4-fold) than the wild-type. Virtually all of the increase in the rate of
      photoactivation can be accounted for by a corresponding 4-fold increase in the
      relative quantum yield of photoactivation as indicated by the yield of
      photoactivation as a function of flash number. The flash frequency dependence of
      photoactivation indicates a multi-quantum process in the mutant resembling the
      wild-type, but with significant increases in yields at all flash frequencies
      examined. The higher quantum yield of photoactivation in delta psbO cells occurs
      in the absence of large changes in the kinetics of the rate-limiting dark
      rearrangement. The results are consistent with increased accessibility (or
      affinity) and photooxidation of Mn2+ at one or both of the two binding sites
      involved in the initial stages of the photoactivation mechanism. In the context
      of previous results, it is proposed that MSP regulates the binding/photooxidation
      of the second Mn2+ of the photoligation sequence, but not the first.

PMID- 8547269
TI  - Amino acid replacements at seven different histidines in the yeast plasma
      membrane H(+)-ATPase reveal critical positions at His285 and His701.
AB  - The plasma membrane H(+)-ATPase (Pmal) from Saccharomyces cerevisiae contains 14
      histidine residues. The seven most highly conserved of these were selected as
      targets for oligonucleotide-directed, site-specific mutagenesis. Substitutions at
      H240, H488, H614, H686, and H914 with a variety of amino acid residues had no
      effect either on cell viability or on temperature and pH growth sensitivity. In
      contrast, substitutions at H701, located in the putative fifth membrane-spanning
      region, with Asp, Gln, or Arg were dominant lethal, indicating that H701 is
      essential for H(+)-ATPase activity. The mutations H285Q and H285R, but not H285E,
      located in the hydrophilic beta-stranded domain, were tolerated in normal growth
      conditions. Growth of H285Q mutants was sensitive to acid pH, indicating impaired
      in vivo ATPase activity. The H285Q and H285R mutants showed increased in vitro
      ATPase-specific activity, increased vanadate resistance, increased proton
      competition of vanadate sensitivity, accelerated ATP hydrolysis rates at a
      substrate concentration much lower than the Km, and slightly uncoupled proton
      pumping. The most reasonable hypothesis which would take into account these
      observations is that H285 would not be involved in the H+ transport process but
      rather in the E2 to E1 transition step of the ATP hydrolysis catalytic cycle.

PMID- 8547270
TI  - Deletions in the interdomain hinge region of flavocytochrome b2: effects on
      intraprotein electron transfer.
AB  - The two distinct domains of flavocytochrome b2 (L-lactate:cytochrome c
      oxidoreductase, EC 1.1.2.3) are connected by a typical hinge peptide. To probe
      the importance of the structural integrity of the hinge region for efficient
      intraprotein electron transfer, three mutant enzymes have been constructed: H
      delta 3 [Sharp, R. E., White, P., Chapman, S. K., & Reid, G. A. (1994)
      Biochemistry 33, 5115-5120], H delta 6, and H delta 9 in which three, six, and
      nine amino acids, respectively, were deleted from the hinge region. Intraprotein
      electron transfer was investigated by steady-state and stopped-flow kinetic
      analyses. All three hinge-deletion enzymes remained good L-lactate
      dehydrogenases, as was evident from steady-state experiments with ferricyanide as
      the electron acceptor and from stopped-flow experiments monitoring flavin
      reduction. The global effect of these deletions is to lower the enzyme's
      effectiveness as a cytochrome c reductase. This property of H delta 6 and H delta
      9 flavocytochromes b2 is manifested at the first interdomain electron-transfer
      step (fully reduced FMN-->heme electron transfer), where the rate of heme
      reduction is the same within experimental error as the steady-state rate of
      cytochrome c reduction. Thus, interdomain electron transfer is rate limiting in
      the case of these two hinge-deletion enzymes compared to the wild-type enzyme,
      where alpha H abstraction from C-2 of L-lactate still contributes substantially
      to rate limitation. The situation for H delta 3 is more complicated, with more
      than one interdomain electron-transfer step being affected. Kinetic data, along
      with the measured deuterium kinetic isotope effects, are discussed in the context
      of the flavocytochrome b2 catalytic cycle and show that complete structural
      integrity within the hinge region is essential for efficient interdomain
      communication.

PMID- 8547271
TI  - Mechanism of inhibition of the plasma membrane Ca(2+)-ATPase by barbiturates.
AB  - We have demonstrated that sodium pentobarbital inhibited the activation of the
      human red blood cell plasma membrane Ca(2+)-ATPase produced by dimerization of
      enzyme monomers or by calmodulin binding to enzyme monomers. The effects of the
      barbiturate were dose-dependent. Both Vmax and Ca2+ affinity were reduced. The
      Ca(2+)-ATPase activity of the dimeric enzyme was distinctly less sensitive with
      respect to the effective inhibitory concentrations of pentobarbital and to the
      rate of onset of inhibition than was the calmodulin-dependent activation of
      enzyme monomers. Temperature dependence of the inhibition was in agreement with
      direct, nonpolar interactions of pentobarbital with a water-exposed nonpolar
      patch on the surface of this transmembrane protein. The barbiturate prevented the
      increase of intrinsic tryptophan fluorescence associated with substrate Ca2+
      binding to the enzyme dimer. On the basis of the barbiturate effects we propose a
      model for the action of detergent-like compounds on the enzyme. They inhibit
      Ca(2+)-ATPase activity by binding to a nonpolar patch on the water-exposed
      dimerization surface of the enzyme monomer, part of which is also the binding
      site for calmodulin. The model assumes that their binding to the nonpolar patch
      on the monomer interferes with dimerization and weakens but does not prohibit
      calmodulin binding, whose activation of the enzyme is then submaximal. The model
      should be applicable to other proteins as the two activation pathways studied
      have been demonstrated for various enzymes.

PMID- 8547272
TI  - Contributions of glycoprotein Ib and the seven transmembrane domain receptor to
      increases in platelet cytoplasmic [Ca2+] induced by alpha-thrombin.
AB  - The individual contributions of glycoprotein Ib (GPIb) and the seven
      transmembrane domain receptor (STDR) to increases in platelet [Ca2+]i induced by
      alpha-thrombin or the tethered ligand peptide (TLP; SFLLRNPNDKYEPF) have been
      determined in control platelets, in platelets where the thrombin binding site on
      GPIb was blocked with the monoclonal antibodies TM60 and LJ-Ib10, in platelets
      where access of thrombin to the STDR was blocked by polyclonal antipeptide
      antibodies, and in Bernard-Soulier platelets which constitutively lack GPIb.
      Curve-fitting analyses (LIGAND) showed that binding of PPACK-thrombin and alpha
      thrombin to the moderate-affinity site was not detected in the best-fit model in
      the presence of anti-STDR antibodies although with alpha-thrombin there was also
      decreased binding at the high-affinity site. Conversely, TM60 blocked binding of
      alpha-thrombin to the high-affinity site but also decreased binding at the
      moderate affinity site. Separately, either TM60 or anti-TNA (150 micrograms/mL)
      reduced thrombin (0.5 nM)-induced elevations in [Ca2+]i to 50% of control values,
      but Ca2+ elevations were essentially abrogated (4.2 +/- 5%) when the two were
      added in combination. [Ca2+]i dose-response curves for alpha-thrombin were
      curvilinear and were only 50% of controls in the presence of anti-GPIb or anti
      STDR antibodies at up to 10 nM alpha-thrombin, with their greatest sensitivity
      being below 2 nM. With Bernard-Soulier platelets, changes in [Ca2+]i were not
      detectable at < or = 0.5 nM alpha-thrombin but were also 50% of controls at 5-10
      nM alpha-thrombin. [Ca2+]i responses to TLP (1-100 microM) of antibody-blocked
      platelets were identical to those of controls whereas responses were
      approximately 50% of controls in Bernard-Soulier platelets. The rate of increase
      in [Ca2+]i in controls was twice that seen in antibody-blocked platelets and
      about 5-fold greater than in Bernard-Soulier platelets. These results demonstrate
      that both GPIb and the STDR are required to ensure the optimal rate and extent of
      platelet activation over a range of alpha-thrombin concentrations (0.3-10 nM) and
      that the STDR corresponds to the previously described moderate-affinity thrombin
      receptor.

PMID- 8547273
TI  - Differentiation of the two forms of GPIb functioning as receptors for alpha
      thrombin and von Willebrand factor: Ca2+ responses of protease-treated human
      platelets activated with alpha-thrombin and the tethered ligand peptide.
AB  - Previous results have shown that both GPIb and the seven transmembrane domain
      receptor (STDR) are required for optimal thrombin-induced platelet activation
      (Greco et al., 1996). Limited degradation (approximately 10%) of GPIb and the
      STDR by elastase reduced the Ca2+ response to 0.5 nM alpha-thrombin by only 10%
      whereas Serratia marcescens metalloprotease reduced the Ca2+ response by 80% and
      fully abrogated high-affinity thrombin binding and aggregation. vWF/ristocetin
      induced agglutination was only slightly reduced (20%) while Ca2+ and aggregation
      response to higher thrombin concentrations were retained. At increasing elastase
      and Serratia protease concentrations, degradation of the STDR proceeded from the
      amino-terminal domain, but Ca2+ responses to the tethered ligand peptide
      SFLLRNPNDKYEPF were not affected by either protease. These results show that both
      putative thrombin receptors are susceptible to protease degradation and suggest
      that Serratia protease is able to differentiate the GPIb-mediated events
      associated with thrombin activation from those associated with ristocetin-induced
      agglutination.

PMID- 8547274
TI  - Preparation and characterization of a disulfide-linked bioconjugate of annexin V
      with the B-chain of urokinase: an improved fibrinolytic agent targeted to
      phospholipid-containing thrombi.
AB  - A conjugate of annexin V and the B-chain of urokinase was prepared and its
      fibrinolytic properties were studied. First, a mutant of annexin V was
      constructed with an N-terminal extension of six amino acids (Met-Ala-Cys-Asp-His
      Ser) and with Cys316 mutated to Ser; this molecule was expressed in Escherichia
      coli. The urokinase B-chain was prepared by limited reduction of the interchain
      disulfide bond between the A- and B-chains of urokinase. These two molecules were
      then then connected by a disulfide bond and purified to yield a 1:1
      stoichiometric conjugate. The conjugate had the same catalytic activity as
      urokinase against a synthetic substrate, Glt-Gly-Arg-MCA, and a similar
      plasminogen activating activity. The conjugate showed the same binding affinity
      for phosphatidylserine-containing membranes as annexin V. The in vitro
      fibrinolytic activity of the conjugates on clots prepared from platelet-rich
      plasma was comparable to that of urokinase. However, the conjugate showed 3-4
      fold stronger in vivo thrombolytic activity than urokinase in a rat pulmonary
      embolism model, while having essentially the same plasma clearance rate as
      urokinase or B-chain. These results show that annexin V is a useful agent for
      targeting plasminogen activators to phospholipid-containing thrombi.

PMID- 8547275
TI  - Heme oxygenase (HO-1): His-132 stabilizes a distal water ligand and assists
      catalysis.
AB  - His-25 and His-132 are the primary candidates for the proximal heme iron ligand
      in heme oxygenase isozyme-1 (HO-1). The unambiguous spectroscopic demonstration
      that His-25 is the proximal iron ligand leaves the role of His-132 uncertain.
      Absorption and resonance Raman spectroscopy are used here to establish that
      mutation of His-132 to an alanine, glycine, or serine does not alter the
      histidine-iron bond, but results in the loss of the water molecule coordinated to
      the distal side of the iron in the wild-type enzyme-substrate complex. The His
      132 mutations also (a) destabilize the ferrous-O2 complex with respect to
      autoxidation, which should result in partial uncoupling of NADPH consumption from
      heme oxidation, and (b) decrease the affinity of the enzyme for heme. The
      catalytic activity of the protein is decreased but not suppressed by these
      mutations: the H132G and H132A mutants retain 40-50% and the H132S mutant 20% of
      the activity of the wild-type protein. His-132, however, is required for
      catalytic turnover of the protein with H2O2. These results place His-132 close to
      the iron on the distal side of the heme pocket and indicate that His-132
      facilitates, but is not absolutely required for, the catalytic turnover of HO-1.

PMID- 8547276
TI  - Influence of core fucosylation on the flexibility of a biantennary N-linked
      oligosaccharide.
AB  - Fluorescence energy transfer was used to study the conformation of each antenna
      of a complex biantennary oligosaccharide. A core fucosylated biantennary
      oligosaccharide was converted to a glycosylamine which allowed coupling of a
      naphthyl donor fluorophore directly to the reducing-end GlcNAc 1. After
      generating an aldehyde at C-6 of residue 6 or 6' using galactose oxidase, a
      dansyl ethylenediamine acceptor fluorophore was coupled to either antenna of the
      oligosaccharide resulting in two donor-acceptor pairs. [Formula: see text] The
      fluorescence properties of the naphthyl group allowed determination of the end-to
      end donor-acceptor distance and antenna flexibility of each isomer by steady
      state and time-resolved fluorescence energy transfer at temperatures ranging from
      0 to 40 degrees C. Extended (20.6 A) and folded (11.4 A) donor-acceptor distance
      populations were identified for the isomer containing dansyl attached to Gal 6',
      whereas only a single extended population (19.7 A) was determined when dansyl was
      attached to Gal 6. The presence of Fuc 1' had a dramatic effect on the
      conformation of the 6' antenna. Temperature modulation failed to alter the ratio
      of extended/folded populations when fucose was present. However, following the
      removal of fucose, the ratio of the extended/folded populations for 6' exhibited
      a temperature dependent conformational equilibrium allowing calculation of the
      enthalpy and entropy of unfolding. These results established a unique
      conformational property for the 6' antenna of a biantennary oligosaccharide that
      is influenced by core fucosylation. Comparison of the results obtained for the 6
      antenna of biantennary with previous fluorescence energy transfer studies on a
      triantennary glycopeptide also established conformational differences in this
      antenna which are dependent on oligosaccharide structure.

PMID- 8547278
TI  - Method for predicting the state of association of discretized protein models.
      Application to leucine zippers.
AB  - A method that employs a transfer matrix treatment combined with Monte Carlo
      sampling has been used to calculate the configurational free energies of folded
      and unfolded states of lattice models of proteins. The method is successfully
      applied to study the monomer-dimer equilibria in various coiled coils. For the
      short coiled coils, GCN4 leucine zipper, and its fragments, Fos and Jun, very
      good agreement is found with experiment. Experimentally, some subdomains of the
      GCN4 leucine zipper form stable dimeric structures, suggesting the regions of
      differential stability in the parent structure. Our calculations suggest that the
      stabilities of the subdomains are in general different from the values expected
      simply from the stability of the corresponding fragment in the wild type
      molecule. Furthermore, parts of the fragments structurally rearrange in some
      regions with respect to their corresponding wild type positions. Our results
      suggest for an Asn in the dimerization interface at least a pair of hydrophobic
      interacting helical turns at each side is required to stabilize the stable coiled
      coil. Finally, the specificity of heterodimer formation in the Fos-Jun system
      comes from the relative instability of Fos homodimers, resulting from unfavorable
      intra- and interhelical interactions in the interfacial coiled coil region.

PMID- 8547277
TI  - Role of glutamate-104 in generating a transition state analogue inhibitor at the
      active site of cytidine deaminase.
AB  - The 19F-NMR resonance of 5-[19F]fluoropyrimidin-2-one ribonucleoside moves
      upfield when it is bound by wild-type cytidine deaminase from Escherichia coli,
      in agreement with UV and X-ray spectroscopic indications that this inhibitor is
      bound as the rate 3,4-hydrated species 5-fluoro-3,4-dihydrouridine, a transition
      state analogue inhibitor resembling an intermediate in direct water attack on 5
      fluorocytidine. Comparison of pKa values of model compounds indicates that the
      equilibrium constant for 3,4-hydration of this inhibitor in free solution is 3.5
      x 10(-4) M, so that the corrected dissociation constant of 5-fluoro-3,4
      dihydrouridine from the wild-type enzyme is 3.9 x 10(-11) M. Very different
      behavior is observed for a mutant enzyme in which alanine replaces Glu-104 at the
      active site, and kcat has been reduced by a factor of 10(8). 5
      [19F]Fluoropyrimidin-2-one ribonucleoside is strongly fluorescent, making it
      possible to observe that the mutant enzyme binds this inhibitor even more tightly
      (Kd = 4.4 x 10(-8) M) than does the native enzyme (Kd = 1.1 x 10(-7) M). 19F-NMR
      indicates, however, that the E104A mutant enzyme binds the inhibitor without
      modification, in a form that resembles the substrate in the ground state. These
      results are consistent with a major role for Glu-104, not only in stabilizing the
      ES++ complex in the transition state, but also in destabilizing the ES complex in
      the ground state.

PMID- 8547279
TI  - Helical periodicity of GA-alternating triple-stranded DNA.
AB  - Homopurine-homopyrimidine tracts (18 or 28 bp) containing predominantly GA
      alternating sequences were inserted between two bent DNA loci composed of six
      (dA)6.(dT)6 repeats. For each homopurine tract, the DNA length between the bent
      DNA loci was varied by one base pair over a full helical turn. The two series of
      bent DNA fragments were electrophoresed in 5% polyacrylamide gel to measure the
      gel mobilities, which reflected the overall extent of DNA bending of each DNA
      fragment. By comparing the gel mobilities between the two series of bent DNA
      fragments, the helical periodicity of the GA-alternating duplex was determined to
      be 10.4 bp/turn. The two series of bent DNA fragments were also electrophoresed
      upon formation of the intermolecular triplex at the homopurine.homopyrimidine
      tracts. Comparison of the gel mobilities between the two series of DNA fragments
      showed that the helical periodicity of triplexed DNA of GA-alternating sequence
      was 11.2 bp/turn. Triplexed DNA with homopurine and homopyrimidine
      oligodeoxyribonucleotides had the same helical periodicity, while hybrid triplex
      DNA associated with homopyrimidine oligoribonucleotide had a slightly more wound
      structure with 11.1 bp/turn.

PMID- 8547280
TI  - Spectral properties of environmentally sensitive probes associated with
      horseradish peroxidase.
AB  - The environmentally sensitive fluorescent probes 6-propionyl-2-(N,N
      dimethylamino)naphthalene (PRODAN) and 2'-(N,N-dimethylamino)-6-naphthoyl-4-trans
      cyclohexanioc acid (DANCA) form complexes with the heme binding site of
      apohorseradish peroxidase. The dissociation constants of the PRODAN and DANCA
      complexes were determined from anisotropy titration data to be approximately 8.7
      x 10(-5) and 3.3 x 10(-4) M, respectively. From comparison of the steady state
      fluorescence spectra of PRODAN and DANCA in solvents of varying dielectric
      constants, and in the apohorseradish peroxidase complex, we conclude that the
      heme binding site of horseradish peroxidase is relatively polar. The lifetimes of
      PRODAN and DANCA in organic solvents of varying polarities can be fit to single
      exponential decays. However, the lifetimes of PRODAN and DANCA associated with
      apohorseradish peroxidase, determined using a background subtraction method to
      correct for the non-negligible fluorescence of unbound probe, fit best to a
      distribution of lifetime values. We attribute these lifetime distributions to
      microenvironmental heterogeneity which is also consistent with the observed
      dependence of the emission maxima of PRODAN-apohorseradish peroxidase upon the
      excitation wavelength. In neither the PRODAN nor the DANCA case was evidence
      found in the time-resolved data for relaxation of the protein matrix around the
      excited state probe dipole.

PMID- 8547281
TI  - Structural study of the interaction between the SIV fusion peptide and model
      membranes.
AB  - It has been shown that there is a correlation between the fusogenecity of
      synthetic peptides corresponding to the N-terminal segment of wild-type and
      mutant forms of simian immunodeficiency virus gp32 (SIV) and their mode of
      insertion into lipid bilayers. Fusogenic activity is only observed when the
      peptide inserts into the bilayer with an oblique orientation. Since bilayer
      destabilization is a necessary step in membrane fusion, we investigate how fusion
      peptides, which insert at different orientations into lipid bilayers,
      structurally affect model membranes. We use X-ray diffraction to investigate the
      structural effects of two synthetic peptides on three different lipid systems.
      One peptide corresponds to the wild-type sequence (SIVwt), which inserts into the
      membrane at an oblique angle and is fusogenic. The other peptide has a rearranged
      sequence (SIVmutV), inserts into the membrane along the bilayer normal, and is
      nonfusogenic. Our results are expressed through different structural effects,
      which depend on the lipid system: for example, (i) disordering of the L alpha
      phase as evidenced by the broadening of the diffraction peaks, (ii) morphological
      convertion of multilamellar vesicles into unilamellar vesicles, (iii) decrease of
      the hexagonal phase cell parameter when SIVwt is added, and (iv) change in the
      conditions for the formation of cubic phases as well as its kinetic stability
      over a range of temperatures. Some of these observations are explicable based on
      the fact that the SIVwt destabilizes bilayers by inducing a negative monolayer
      curvature, while the SIVmutV destabilizes bilayers by inducing a positive
      monolayer curvature. Finally, we present a model which describes how these
      findings correlate with fusogenic activity and fusion inhibitory activity,
      respectively.

PMID- 8547282
TI  - Identification of the epitope for monoclonal antibody 4B1 which uncouples lactose
      and proton translocation in the lactose permease of Escherichia coli.
AB  - Monoclonal antibody 4B1 binds to a conformational epitope on the periplasmic
      surface of the lactose permease of Escherichia coli, uncoupling lactose and H+
      translocation in a manner indicating that it blocks deprotonation [Carrasco, N.,
      Viitanen, P., Herzlinger, D., & Kaback, H. R. (1984) Biochemistry 23, 3681;
      Herzlinger, D., Viitanen, P., Carrasco, N., & Kaback, H. R. (1984) Biochemistry
      23, 3688]. In this paper, 4B1 binding to purified lactose permease is shown to
      exhibit a KD of about 5 x 10(-10) M by surface plasmon resonance. Furthermore,
      the combined use of mutants containing 6 contiguous His residues in each
      periplasmic loop in the permease and Cys-scanning mutagenesis in conjunction with
      chemical labeling demonstrates that 4B1 binds specifically to the periplasmic
      loop between helices VII and VIII and that Phe247 and Gly254 are the primary
      determinants. Remarkably, although 4B1 binding uncouples lactose and H+
      translocation, none of the amino acid residues in periplasmic loops, particularly
      Phe247 or Gly254, play an important role in the transport mechanism. Moreover,
      binding of avidin to biotinylated Glu255-->Cys in the loop containing the epitope
      has no effect on transport activity. Therefore, the uncoupling effect of 4B1
      involves highly specific interactions which in all likelihood exert a torsional
      effect on the loop, resulting in a conformational change in helix VII and/or VIII
      that alters the pKas of residues involved in lactose-coupled H+ translocation.

PMID- 8547283
TI  - Topological disposition of tyrosine 486 in anion exchanger from human
      erythrocytes.
AB  - The location with respect to the plasma membrane of tyrosine 486 in the native
      anion exchanger of human erythrocytes has been determined by site-directed
      immunochemistry. Intact erythrocytes and inside-out vesicles were
      [125I]radioiodinated by lactoperoxidase in the same vessel. After the
      erythrocytes and inside-out vesicles had been separated by differential
      centrifugation, the modified polypeptide of the anion exchanger was isolated from
      each sample and digested with the proteinase from Staphylococcus aureus strain V8
      and trypsin to generate the peptide YIVGR. An immunoadsorbent that was specific
      for the carboxy-terminal sequence -IVGR was used to purify the peptide YIVGR,
      which contains tyrosine 486 of the anion exchanger, from the products of the
      digestion. The [125I]radioiodinated peptides isolated by the immunoadsorbent were
      submitted to high-pressure liquid chromatography, and their respective mobilities
      were compared to those of synthetic peptides that had been iodinated at tyrosine.
      By applying this technique, the peptide containing tyrosine 486 was unambiguously
      identified, and the incorporation of [125I]iodine into this residue in anion
      exchanger could be monitored. When inside-out vesicles and intact cells were
      [125I]radioiodinated in the same suspension, tyrosine 486 was modified to at
      least a 6-fold greater specific radioactivity in the inside-out vesicles than it
      was in the intact cells. This amino acid, therefore, was assigned to the
      cytoplasmic surface of native anion exchanger. It follows that the polypeptide of
      anion exchanger spans the membrane three times before it reaches the
      extracellular region surrounding glutamine 550.

PMID- 8547284
TI  - Histomorphologic analysis of the soft palate musculature in prenatal cleft and
      noncleft A/Jax mice.
AB  - The two specific aims of this study were as follows: to evaluate the
      appropriateness of the A/Jax mouse model in the investigation of the key cellular
      stages in prenatal soft palate morphogenesis and myogenesis; and to describe
      structural differences in the histomorphology of the soft palate anatomy from
      cleft and noncleft mice prior to, during, and after palatogenesis. Cleft-induced
      and control groups of A/Jax mouse embryos from timed pregnancies were harvested
      sequentially on gestational days 15 to 19. Embryos were weighed and staged for
      external body morphology. The heads were removed and fixed for light microscopy,
      sectioned serially in the frontal plane at 10 microns and stained with
      hematoxylin-eosin to characterize and compare the soft palate musculature. All
      observations were made at the head depth of the trigeminal ganglion in both age-
      and stage-matched embryos. The following findings were made: (1) the A/Jax mouse
      is a suitable animal model for the study of soft palate myogenesis; (2) there
      were no discernible morphologic differences between the soft palate muscles in
      cleft and noncleft A/Jax mice when viewed under light microscopy; (3) the soft
      palate and related muscles were identifiable as muscle fields, in both the cleft
      and noncleft fetuses, as early as gestational day 15 and as specific muscles at
      gestational day 18; (4) in both the cleft and noncleft A/Jax fetuses, the soft
      palate muscles appeared in a sequential anatomic fashion (the palatine
      aponeurosis appeared first, next the tensor palatini, and then the levator
      palatini muscles); and (5) in the cleft palate fetuses, both pterygoid plates
      were angulated and displaced laterally.

PMID- 8547285
TI  - Longitudinal study on three-dimensional changes of facial asymmetry in children
      between 4 to 12 years of age with unilateral cleft lip and palate.
AB  - The purpose of the present study was to describe three-dimensional developmental
      changes of facial asymmetry in children with an operated complete unilateral
      cleft lip and palate (UCLP) and in children without craniofacial anomalies
      (controls). Using stereophotogrammetry, three-dimensional coordinates for 16
      bilateral and 10 midsagittal facial landmarks were determined for the UCLP group
      (n = 33) and the control group (n = 63) on two occasions. In this mixed
      longitudinal study, the children were 4 to 12 years of age. Facial asymmetry and
      left-right dominance was measured and resolved for transverse, vertical, and
      sagittal components. Significant effects were analyzed with multivariate analyses
      of variance (MANOVA). We concluded that individuals with complete unilateral
      cleft lip and palate, as well as individuals without craniofacial anomalies, show
      an increase, during growth, in the amount of facial asymmetry in the basal region
      of the nose. In the region that is related to the cleft, children with complete
      unilateral cleft lip and palate do not show changes in the amount of facial
      asymmetry between the occasions. Regarding facial left-right dominance and
      variation in dominance, no demonstrable growth changes take place in individuals
      with complete cleft lip and palate, nor in individuals without craniofacial
      anomalies.

PMID- 8547286
TI  - Do palatal lift prostheses stimulate velopharyngeal neuromuscular activity?
AB  - The purpose of this investigation was to evaluate the ability of palatal lift
      prostheses to stimulate the neuromuscular activity of the velopharynx.
      Nasendoscopic evaluations were audio-videotaped preprosthetic and postprosthetic
      management for 25 patients who underwent placement of a palatal lift prosthesis
      for velopharyngeal dysfunction (VPD). These audio-videotapes were presented in
      blinded fashion and random order to three speech pathologists experienced in
      assessment of patients with VPD. They rated the tapes on the following
      parameters: VP gap size, closure pattern, orifice estimate, direction and
      magnitude of change, and qualitative descriptions of the adequacy of VP closure
      during speech. VP closure for speech was unchanged in 69% of patients and the
      number of patients rated as improved or deteriorated was nearly identical at
      about 15%. Postintervention gap shape remained unchanged in 70% of patients. The
      extent of VP orifice closure during speech remained unchanged in 57% of patients.
      Articulations that could impair VP function improved in 30% of patients,
      deteriorating in only 4%. Results of this study neither support the concept that
      palatal lift prostheses alter the neuromuscular patterning of the velopharynx,
      nor provide objective documentation of the feasibility of prosthetic reduction
      for weaning.

PMID- 8547287
TI  - Velopharyngeal incompetence and persistent hypernasality after adenoidectomy in
      children without palatal defect.
AB  - Persistent hypernasal speech after adenoidectomy has been reported in children
      with palatal deficiency. Hypernasality after adenoidectomy can also occur in
      children with normal palatal function. The aim of the present study was to
      identify the cause of velopharyngeal incompetence and hypernasality after
      adenoidectomy in children who did not have palatal defect as a predisposing
      factor. Sixteen children who developed hypernasality after adenoidectomy were
      included in the present study. Standard lateral cephalometry, videofluoroscopy,
      and nasopharyngoscopy were performed to visualize the velopharynx and its
      function during speech. The results showed that enlarged tonsils and prominent
      remaining adenoid tissue on the posterior pharyngeal wall were the causes of
      hypernasality in these children. Incomplete removal of the adenoid tissue should
      be avoided and enlarged tonsils should be removed at the time of adenoidectomy to
      prevent the risk for postoperative hypernasality.

PMID- 8547288
TI  - Transverse maxillary arch changes with the use of preoperative orthopedics in
      unilateral cleft palate infants.
AB  - A retrospective clinical study, using a reflex microscope, measured arch widths,
      palatal shelf widths, cleft widths, and palatal shelf angulation from 26 sets of
      plaster models of infants' maxillary arches at birth, and at 3 and 6 months. All
      infants had unilateral clefts of the lip and palate. They were treated with
      active preoperative orthopedics until lip repair at 3 months and with a passive
      plate until palate repair. Cleft width significantly decreased during these
      periods, due to transverse growth, along with relative flattening of the palatal
      shelves. Arch width contracted slightly anteriorly, but remained stable
      posteriorly. Preoperative orthopedics may have helped these changes by removing
      the effects of the tongue action and allowing unrestricted growth of the palatal
      shelves.

PMID- 8547289
TI  - Craniosynostosis with joint contractures, ear deformity, cleft palate, scoliosis,
      and other features.
AB  - A case of craniosynostosis with joint contractures, ear deformity, cleft palate,
      scoliosis, and many other features is presented. The patient's skull was round
      with craniosynostosis of the coronal suture. The fingers were slender and long;
      the finger joints were contracted. Trismus was also present. Contracture of the
      temporomandibular joint was suspected. The helices were flat, antihelices were
      minimal, and the ears protruded. Furthermore, the facial and cranial features of
      this patient included mild hypertelorism, ocular proptosis, short pons nasi, flat
      radix nasi, mild retrognathia, and small oral fissure. In the oral cavity, a
      relatively wide cleft extended from the soft palate to the uvula. A frontal chest
      radiograph revealed a mild scoliosis. Differential diagnoses are discussed in
      reported syndromes with craniosynostosis.

PMID- 8547290
TI  - Ethical decision-making in interdisciplinary team care.
AB  - Most clinical and ethical decisions are made between a patient and his or her
      physician. However, patients with complex or chronic medical problems are often
      cared for by a team of professionals from multiple disciplines. Little is known
      about the process of making ethical decisions between patients and teams of
      health care providers. The purposes of this article are to examine the process of
      collective decision-making in interdisciplinary patient care, to present a model
      for clinical and ethical decision-making, and finally, to discuss ethical
      decision-making in team care. The benefits and potential risks of
      interdisciplinary care are discussed and illustrated with case examples. Cleft
      palate and craniofacial teams are used as a model of interdisciplinary team care.

PMID- 8547291
TI  - Neonatal intensive care as a locus for ethical decisions.
AB  - Children born with congenital anomalies are usually cared for in the neonatal
      intensive care unit (NICU). Although most of these children will have conditions
      amenable to surgical correction, many will have serious underlying disorders that
      will alter the approach to management of the secondary birth defects and the
      child. The decision as to whether to treat or withhold treatment from a child
      with congenital anomalies lies with the parents or legal guardians with guidance
      and counseling from the health and medical care givers. The ability to make a
      rational decision about whether or not to offer treatment depends upon the
      ability to make a correct diagnosis, understand the implications of the
      diagnosis, and to be able to communicate this information to the patient's
      family. This responsibility, in many centers, falls upon the shoulders of the
      clinical geneticist. There is a critical need for clear communication among care
      givers who comprise the management team and between the management team and the
      family. Major obstacles that can arise include lack of communication among care
      givers and the reluctance of family members to make decisions regarding
      withholding treatment despite a diagnosis of a condition with a grave prognosis.
      As our technology improves, our ability to save the lives of the smallest and
      sickest infants will increase; the greatest dilemma, however, which we will face
      will not be whether we can treat, but rather, whether we should treat certain
      conditions and how these decisions will be made.

PMID- 8547292
TI  - Craniofacial surgery and the ethics of decision-making.

PMID- 8547293
TI  - Family focused ethics.
AB  - It is my intent to explore the family, parent, patient, social work relationships
      as a focus central to the solution of ethical dilemmas. In today's environment,
      patient selection continues to reflect persistent patterns of biased allocation
      of services. The ability of a family to make a decision about medical treatment
      begins with an understanding of how choices regarding that treatment are shared.
      Without taking appropriate precautions, an increased risk arises of providing
      surgical procedures involving real medical risk, yet unresolved psychological
      trauma remains unassessed. The unrelenting questions of, When?, How?, and Why?, a
      family should be involved in the process of ethical decision-making, begs the
      inherent prejudice involved.

PMID- 8547294
TI  - Who decides? Patients, parents, or gatekeepers: pediatric decisions in the
      craniofacial setting.
AB  - Special ethical issues arise for the craniofacial team dealing with pediatric
      patients, which include competency, surrogacy, and the "best interests" standard.
      Medical decisions for children are made by surrogates, usually parents, who must
      use the "best interests" standard. The team's primary responsibility is to the
      child, not the parents. Children should participate as abilities allow,
      especially for elective procedures. Increasingly, cost considerations also
      influence medical decisions. The craniofacial team is often a de factor
      gatekeeper. Ethically responsible team behavior includes: weighing risks and
      benefits of proposed interventions; promoting discussion with families and
      patients to identify "best interests;" monitoring outcomes; and advocacy for
      craniofacial patients individually and at a policy level. Care guidelines and
      definitions of basic levels of care should be developed to assist teams with
      decision-making and advocacy efforts. Ethical analysis is part of both good
      patient care and good policy formation, and should be a part of regular team
      deliberations.

PMID- 8547295
TI  - Resource allocation, health policy, and rationing craniofacial care.
AB  - The United States allocates health care without an overt system of rationing.
      This article analyzes the forces that guide resource allocation to craniofacial
      care. Various possible allocation systems are reviewed for how decision makers
      might evaluate proposed programs for legislative funding. Using a case-based
      exercise, readers are asked to weigh the potential costs and benefits of six
      health and social programs. These programs are also systematically examined for
      factors that are likely to affect resource allocation decisions. Eleven factors
      that affect decision-making are utilized in the analysis, ranging from the cost
      per client to emotional or human interest content of the proposed programs.
      Decisions about preventive programs are compared with those involving therapeutic
      programs. The allocation of resources to craniofacial programs, including those
      for children with rare major craniofacial conditions, is considered in the
      context of social justice and broad contemporary ethical and health care delivery
      issues.

PMID- 8547296
TI  - Common molecular pathways for patterning of the body axis, limbs, central nervous
      system, and face during embryonic development.
AB  - Many congenital anomalies affecting the face are known to appear as syndromes or
      associations, in combination with other defects. Often, these involve the limbs,
      eyes, central nervous system, and body axis. A general, and understandable,
      tendency among clinical researchers has been to seek a single cell type or
      definable embryologic process on which to ascribe the etiologic basis for such
      associations. The possibility of a gene, or group of genes, under coordinate
      control has not received much attention until recently. With the advent of
      recombinant DNA technology and the current explosion in basic research on the
      molecular bases of embryonic development, however, several possibilities are
      beginning to emerge. Here, I will list a few genes whose expression during
      development suggests that the molecules they encode are used as part of a
      coordinate molecular pathway, and that they play a role in the development of
      systems that often appear together in congenital associations or syndromes.

PMID- 8547297
TI  - Confleunce of clinical, theoretical, and laboratory research in syndromology.

PMID- 8547298
TI  - Congenital oral adhesion (syngnathia) with total cleft palate in a Nigerian
      child.

PMID- 8547299
TI  - Vesicle-forming synthetic amphiphiles.

PMID- 8547300
TI  - Transport of proteins across membranes--a paradigm in transition.

PMID- 8547301
TI  - Intracellular membranes in the synthesis, transport, and metabolism of
      proteoglycans.

PMID- 8547302
TI  - The role of the MDR protein in altered drug translocation across tumor cell
      membranes.

PMID- 8547303
TI  - The epithelial mucin, MUC1, of milk, mammary gland and other tissues.
AB  - MUC1 is a mucin-type glycoprotein that is integrally disposed in the apical
      plasma membrane of the lactating epithelial cell and protrudes from the cell
      surface into the alveolar lumen where milk is stored. Envelopment of milk fat
      globules by this membrane accomplishes their secretion and conveys MUC1 into
      milk. The human form of this mucin has been detected in many other organs,
      tissues and body fluids. It projects from the cell surface as long filaments. In
      the human and a number of other species, MUC1 is polymorphic due to variable
      numbers of a tandemly repeated segment 20 amino acids in length. The individual
      codominantly expresses two alleles for the mucin so that differences in its size
      among individuals and between the two forms of an individual are observed. The
      tandem repeats are rich in serines and threonines which serve as O-glycosylation
      sites. Carbohydrate content of MUC1, as isolated from milk of human, bovine and
      guinea pig, is approximately 50%. The oligosaccharides carry substantial sialic
      acid at their termini and this accounts for two putative functions of this mucin,
      i.e., to keep ducts and lumens open by creating a strong negative charge on the
      surface of epithelial cells which would repel opposite sides of a vessel, and to
      bind certain pathogenic microorganisms. MUC1 is protease resistant (trypsin,
      chymotrypsin and pepsin) and large fragments of it can be found in the feces of
      some but not all breast-fed infants. MUC1 has a highly varied structure because
      of its polymorphism, qualitative and quantitative variations in its glycosylation
      between tissues, individuals and species, and differences due to divergence in
      the nucleotide sequences among species. Sequencing of the MUC1 gene for various
      species is showing promise of revealing unique evolutionary relationships and has
      already indicated conserved aspects of the molecule that may be functionally
      important. Among these are positions of serine, threonine and proline in the
      tandem repeats and a high degree of homology in the transmembrane and cytoplasmic
      segments of the molecule.

PMID- 8547304
TI  - Signalling and transport through the nuclear membrane.

PMID- 8547305
TI  - Molecular and functional properties of mitochondrial benzodiazepine receptors.

PMID- 8547306
TI  - Characterization of the Pseudomonas aeruginosa transposable bacteriophage D3112 A
      and B genes.
AB  - The left end DNA of Mu-like transposable bacteriophage D3112 was sequenced from
      bp 2521 to bp 5483. Two large open reading frames were identified: ORF A (bp 2539
      4611) and ORF B (bp 4626-5378). ORF A can encode a 690 amino acid, 78 kDa protein
      which is 44.4% similar to Mu transposase and ORF B can encode a 250 amino acid,
      27 kDa protein, which is 46.4% similar to, though 62 amino acids shorter than,
      the Mu B protein. The cloned D3112 A gene exhibited activity on a mini-D3112
      containing plasmid in Pseudomonas aeruginosa.

PMID- 8547307
TI  - Cloning and sequencing of a tpr-met oncogene cDNA isolated from MNNG-transformed
      human XP fibroblasts.
AB  - A rearranged tpr-met oncogene was identified in a MNNG-transformed human
      Xeroderma pigmentosum (XP) cell line (ASKMN). A 2016 bp cDNA was cloned and
      sequenced, disclosing an ORF with a coding capacity for a 523 aa protein. The
      sequence of this tpr-met cDNA was very similar to that previously reported in
      another human MNNG-transformed cell line (MNNG-HOS).

PMID- 8547308
TI  - Zebrafish cyclin D1 is differentially expressed during early embryogenesis.
AB  - We have isolated and determined the nucleotide sequence of a cDNA containing the
      complete coding region of cyclin D1 from embryonic zebrafish cDNA library. The
      cyclin D1 gene is a single copy gene within the zebrafish genome, which undergoes
      an alternative polyadenylation process. The initial expression of cyclin D1
      transcript occurs at the presumed onset of G1 phase in the developing zebrafish
      embryo.

PMID- 8547309
TI  - Cloning of cDNA for rat eosinophil major basic protein.
AB  - We have determined the complete nucleotide sequence for the cDNA encoding rat
      eosinophil major basic protein (MBP) using the rapid amplification of cDNA ends
      (RACE) procedure. The deduced amino acid sequence revealed that the rat prepro
      MBP has three functional domains, namely the signal peptide, the acidic peptide
      that contains numerous acidic amino acids, and the mature MBP, as in human and
      guinea pig MBP.

PMID- 8547310
TI  - Cloning and sequence analysis of human guanidinoacetate N-methyltransferase cDNA.
AB  - In a child with severe muscular hypotonia and extrapyramidal movement disorder,
      elevation of guanidinoacetate and deficiency of creatine in brain suggested a
      defect in biosynthesis of creatine at the level of guanidinoacetate
      methyltransferase (GAMT) (Stockler, S. et al. (1994) Pediatr. Res. 36, 409-413).
      As a first step in the molecular analysis of GAMT deficiency, the cDNA for human
      GAMT was cloned using rat GAMT cDNA as a probe. For the coding region there is a
      82.5% homology of the nucleotide sequence and 86.9% homology of the deduced amino
      acid sequence between human and rat.

PMID- 8547311
TI  - Cloning and expression analysis of the murine Rab7 cDNA.
AB  - A cDNA clone coding for the Rab7 protein was isolated from an NIH3T3 cell line
      (mouse fibroblasts) cDNA library. Sequence analysis shows high homology to the
      rat and dog cDNAs. Northern blot analysis showed the presence of two messenger
      RNA that differ at the 3' untranslated region.

PMID- 8547312
TI  - The two alleles of the hapP gene in Physarum polycephalum code for different
      proteins.
AB  - Many mRNAs show cell-type specific expression in the acellular slime mold
      Physarum polycephalum. The most abundant plasmodial-specific mRNA (hapP) encodes
      a small hydrophobic protein of 187 amino acids that contains a potential signal
      peptide. Southern hybridizations using the hapP cDNA showed that the hapP gene is
      a single copy gene with two alleles, hapP1 and hapP2. The alleles have
      restriction enzyme polymorphisms. The nucleotide sequence of the coding region of
      the hapP1 allele was obtained from a genomic clone, and the nucleotide sequence
      of the hapP2 allele was obtained from a cDNA clone. The hapP1 and hapP2 alleles
      code for proteins that are 9.6% different in amino acid sequence. All differences
      are found in the central region of the protein. The nucleotide sequences of the
      first and last exons, which contain coding and non-coding regions, are identical.
      PCR amplification of cDNAs (RT-PCR) showed that both alleles are expressed in the
      same cell.

PMID- 8547313
TI  - Identification and characterization of the v-cath gene of the baculovirus,
      CfMNPV.
AB  - The v-cath gene of the Autographa californica multi-nucleocapsid nuclear
      polyhedrosis virus (AcMNPV) encodes a cathepsin L-like proteinase which plays a
      role in the liquefaction of host tissues during a viral infection [1]. We have
      identified a homologous gene in the spruce budworm virus, Choristoneura
      fumiferana MNPV (CfMNPV). The CfMNPV v-cath gene is 74% identical to AcMNPV v
      cath at the nucleotide sequence level and 80% identical at the level of predicted
      amino acid sequence. Transcription analysis of the CfMNPV v-cath gene revealed
      that it is expressed late in infection and that transcription initiates within
      the consensus baculovirus late-promoter motif.

PMID- 8547314
TI  - Cloning and sequencing of the gene coding for topoisomerase I from the extremely
      thermophilic eubacterium, Thermotoga maritima.
AB  - A 2767 bp fragment containing a gene coding for a topoisomerase I from the
      extremely thermophilic eubacterium Thermotoga maritima (Tm TopA) has been cloned
      and sequenced. The protein is composed of 633 amino acids with a calculated
      molecular mass of 72,695 Da. It shares significant similarity with the
      topoisomerases I of mesophilic eubacteria. The highest score is obtained with
      Bacillus subtilis (44% identity); in particular, T. maritima and B. subtilis
      possess an insertion of 7-8 amino acids in the vicinity of the active site, that
      is absent in topoisomerases of other organisms. A specific feature of T. maritima
      topoisomerase I is its low cysteine content compared to its mesophilic homologs.
      It contains 5 cysteine residues, of which 4 could constitute a zinc finger motif.
      Finally, analysis of the regions flanking the gene reveals that Tm TopA is
      surrounded by two other ORFs, suggesting the occurrence of a polycistronic
      transcriptional unit.

PMID- 8547315
TI  - Structural and functional analysis of the human phosphoenolpyruvate carboxykinase
      gene promoter.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the rate limiting step in
      hepatic and renal gluconeogenesis. Glucagon (acting via cyclic AMP (cAMP)) and
      glucocorticoids stimulate PEPCK gene transcription, whereas insulin has the
      opposite effect. Since these are the major regulatory hormones controlling
      glucose homeostasis, and because increased hepatic glucose production is one of
      the characteristics of non-insulin dependent diabetes mellitus (NIDDM),
      investigators have speculated that the regulation of PEPCK gene expression may be
      defective in patients with NIDDM. To begin to investigate this possibility we
      have isolated and sequenced the human PEPCK gene promoter. In addition, we have
      constructed and analyzed a human PEPCK promoter-chloramphenicol acetyltransferase
      (CAT) fusion gene in an effort to correlate differences between the rat and human
      promoter sequences and the hormonal regulation of transcription.

PMID- 8547316
TI  - Partial amino acid sequence of an L-amino acid oxidase from the cyanobacterium
      Synechococcus PCC6301, cloning and DNA sequence analysis of the aoxA gene.
AB  - A novel type of L-amino acid oxidase from Synechococcus PCC6301 was purified and
      subjected to amino acid sequence analysis. Since the N-terminus of the L-amino
      acid oxidase protein was not accessible for Edman degradation, the protein was
      partially hydrolysed and a contiguous sequence of 17 amino acid residues was
      obtained from an endogenous peptide fragment. Based on the partial peptide
      sequence two oligonucleotides were designed, which were used as probes in
      Southern hybridization experiments in order to identify the corresponding aoxA
      gene. The aoxA gene was isolated from a size-fractionated genomic library of
      Synechococcus PCC6301 and subsequently sequenced. From the nucleotide sequence
      (data base accession number Z48565) it can be deduced that the L-amino acid
      protein consists of 355 amino acid residues resulting in a molar mass of 39.2
      kDa. The calculated isoelectric point of the protein is 9.81. The L-amino acid
      oxidase from Synechococcus PCC6301 shows low homologies to other flavin
      oxidases/dehydrogenases, especially amine oxidases, but no homologies to other so
      far sequenced L- or D-amino acid oxidases.

PMID- 8547317
TI  - Identification of transcriptionally induced Z-DNA segments in the human c-myc
      gene.
AB  - Using monoclonal antibodies against Z-DNA three AluI restriction fragments of the
      human c-myc gene were previously found to form Z-DNA in agarose-embedded,
      metabolically active permeabilized nuclei. The formation of Z-DNA in these
      fragments was dependent on negative supercoiling generated by transcription of
      the gene. Here we show which sequence elements of these three AluI restriction
      fragments adopt the Z conformation upon negative supercoiling. The three
      fragments (Z1, Z2 and Z3) were inserted in a suitable plasmid vector. Z-DNA
      forming elements were detected by comparing DEPC reactivity in relaxed circular
      and supercoiled plasmid DNA. Z1 and Z3 each contained one major Z-DNA forming
      region 20-25 nucleotides long, whereas Z2 contained two discrete regions 90
      nucleotides apart one about 35 nucleotides the other about 20 nucleotides long.

PMID- 8547318
TI  - Expression of recombinant elongation factor 1 beta from rabbit in Escherichia
      coli. Phosphorylation by casein kinase II.
AB  - The beta subunit of eukaryotic elongation factor 1 (EF-1) catalyzes the GDP/GTP
      exchange activity on EF-1 alpha. In these studies, two cDNAs for the beta subunit
      of EF-1 from rabbit are cloned and sequenced. The cDNAs consist of 808 and 798 bp
      and are identical except for the 5' leader sequences of 67 and 57 bp. Both cDNAs
      code for a protein of 225 amino acids. Using the pT7-7 expression vector, EF-1
      beta was expressed in Escherichia coli and purified to apparent homogeneity by
      chromatography on DEAE-cellulose and FPLC on Superose 12 and Mono Q. EF-1 beta
      was highly phosphorylated by casein kinase II, with up to 1.3 mol of phosphate
      incorporated per mol protein. From microsequence analysis and manual Edman
      degradation, the majority of the phosphate was shown to be present in serine 106
      in the peptide DLFGS106DDEEES112EEA. Serine 112 was also phosphorylated by casein
      kinase II, but to a lesser extent. Previously, little phosphorylation of the beta
      subunit by casein kinase II was observed in native EF-1 unless GDP was bound to
      the alpha subunit (Palen, E., Venema, R.C., Chang, Y-W.E. and Traugh, J.A. (1994)
      Biochemistry, 8515-8520). In contrast, purified recombinant EF-1 beta was highly
      and specifically phosphorylated by casein kinase II; GDP and polylysine had
      little effect on the rate of phosphorylation of the purified subunit.

PMID- 8547319
TI  - Polyubiquitin in crustacean striated muscle: increased expression and conjugation
      during molt-induced claw muscle atrophy.
AB  - The claw muscles of decapod crustaceans undergo a molt-induced atrophy to
      facilitate withdrawal of the claws at ecdysis. Polyubiquitin expression, as well
      as the levels of ubiquitin conjugates, a ubiquitin-conjugating enzyme involved in
      the ATP/ubiquitin-dependent proteolytic pathway (crustacean E2(16 kDa) homolog of
      Drosophila UbcD1), and proteasome, were examined to determine the role of
      ATP/ubiquitin-dependent proteolysis in the enhanced degradation of myofibrillar
      proteins during muscle atrophy. A partial-length clone (1.7 kb) of polyubiquitin
      was isolated from a lobster muscle cDNA library; the 5' end lacked the 5'
      untranslated region (UTR) and the beginning of the first ubiquitin monomer, while
      the 3' end contained the terminal ubiquitin monomer and 3' UTR. The deduced amino
      acid sequence was 100% identical with that from Manduca, Drosophila, and human.
      In land crab claw muscle, the polyubiquitin mRNA (2.7 kb) increased about 5-fold
      and ubiquitin-protein conjugates (> 200 kDa) increased about 8-fold during
      atrophy. In contrast, the level of a ubiquitin-conjugating enzyme (E2(16 kDa))
      remained unchanged. The proteasome, which constitutes the catalytic core of the
      ATP/ubiquitin-dependent proteinase complex, increased about 2-fold during
      proecdysis, reaching its highest level immediately before ecdysis. These results
      suggest that the ATP/ubiquitin-dependent proteolytic pathway contributes to the
      changes in protein metabolism that occur during molt-induced muscle atrophy.

PMID- 8547320
TI  - Formation of a free radical of the sulfenylimine type in the mouse ribonucleotide
      reductase reaction with 2'-azido-2'-deoxycytidine 5'-diphosphate.
AB  - Mouse and Escherichia coli ribonucleotide reductases (RR) both belong to the same
      class of RR, where the enzyme consists of two non-identical subunits, proteins R1
      and R2. A transient free radical was observed by EPR spectroscopy in the mouse RR
      reaction with the suicidal inhibitor 2'-azido-2'-deoxycytidine 5'-diphosphate.
      The detailed hyperfine structure of the EPR spectrum of the transient radical is
      somewhat different for the mouse and previously studied E. coli enzymes. When the
      positive allosteric effector ATP was replaced by the negative effector dATP, no
      transient radical was observed, showing that 'normal' binding of the inhibitor to
      the substrate binding site is required. Using the mouse protein R2 mutants W103Y
      and D266A, where the mutations have been shown to specifically block long range
      electron transfer between the active site of the R1 protein to the iron/radical
      site in protein R2, no evidence of transient radical was found. Taken together,
      the data suggest that the radical is located at the active site in protein R1,
      and is probably of the sulfenylimine type.

PMID- 8547321
TI  - Characterization of the binding of HU and IHF, homologous histone-like proteins
      of Escherichia coli, to curved and uncurved DNA.
AB  - The binding of E. coli histone-like protein HU to curved and uncurved DNA
      fragments containing adenine tracts was characterized by relative binding
      affinity assay, and compared with that of other homologous histone-like protein
      integration host factor (IHF). Both HU and IHF have about 3- to 5-fold higher
      affinity for overall curved DNA fragments such as (A6N4)11 and (A3T3N4)12
      compared to a standard duplex fragment with mixed sequence. The binding manner of
      HU to the curved fragments was highly cooperative. However, loss of overall
      curvature for shorter fragments (< approximately 100 bp) reduced the preference
      of HU binding to curved (A3T3N4)n over uncurved (T3A3N4)n, indicating that the
      binding specificity of HU to curved DNA is length-dependent. Thus, the curved DNA
      configuration of the whole molecule facilitates the binding of several HU
      molecules to form the hierarchy of HU-DNA complex. Furthermore, it was shown that
      HU and IHF bind less well to (A6N9)n, which has a zig-zag straight structure,
      whereas they preferentially bind to uncurved (T3A3N4)14. These results suggested
      that not only intrinsically overall curvature but also the preferred orientations
      for DNA bending in the protein-DNA complex are important factors for affinities
      of HU and IHF.

PMID- 8547322
TI  - Differential expression of DNA topoisomerases in non-small cell lung cancer and
      normal lung.
AB  - DNA topoisomerases are ubiquitous nuclear enzymes, and important targets of
      cancer chemotherapy. Expression of topoisomerase genes is often correlated with
      in vitro chemosensitivity. We investigated the expression of the topoisomerase
      genes in normal lung and non-small cell lung cancer. Expression of topoisomerase
      II-alpha, topoisomerase II-beta, and topoisomerase I genes has been assessed in
      tumor samples of 60 patients who underwent operation for a non-small cell lung
      carcinoma, by RNase protection assay, and by immunohistochemistry. The expression
      of topoisomerase II-alpha gene was either undetectable or very low in normal
      lung, while most NSCLC expressed readily quantifiable levels of this gene. No
      alteration of the topoisomerase II-alpha gene was found by Southern blotting in
      the NSCLC samples. In contrast to topoisomerase II-alpha, topoisomerase II-beta
      was expressed in most normal as well as in tumor tissue samples, at a similar
      level. The levels of expression of both topoisomerase II isoforms was lower than
      that of human lung cancer cell lines. The results of the topoisomerase II mRNA
      expression were confirmed by immunohistochemistry. Whereas topoisomerase II-alpha
      staining was mainly limited to the nucleus, staining with topoisomerase II-beta
      antibody was exclusively observed in nucleoli. Topoisomerase I was localized in
      the nuclei and expression was mainly limited to tumor cells. By RNase protection,
      topoisomerase I expression in NSCLC samples was in the range of that of human
      lung cancer cell lines. The expression of the topoisomerase genes did not seem to
      be coordinated. In tumor cells, there was a positive association between
      expression of topoisomerase II-alpha and Ki-67, a marker of cell proliferation,
      as assessed by immunohistochemistry, but not with topoisomerase II-beta or
      topoisomerase I. Clinical characteristics of the patients, and their survival did
      not appear to be correlated to the level of expression of any of the
      topoisomerase genes, although a trend towards a shorter survival was observed in
      patients whose tumors expressed relatively high topoisomerase II-alpha mRNA
      levels. IN CONCLUSION: (1) the two isoforms of topoisomerase II are
      differentially expressed in normal lung and NSCLC cells; (2) higher topoisomerase
      II-alpha expression is associated with higher cell proliferation in NSCLC; (3)
      the expression of topoisomerase II-alpha and topoisomerase I, but not of
      topoisomerase II-beta, was higher in tumor cells compared to normal lung. Given
      the differential expression of topoisomerases in normal lung and tumors, research
      of more potent and specific topoisomerase inhibitors might prove beneficial in
      non-small cell lung cancer. Immunohistochemistry may be indicated in
      prospectively investigating the correlation between expression of topoisomerases
      and results of chemotherapy treatment.

PMID- 8547324
TI  - Electroporation-induced damage in mammalian cell DNA.
AB  - Electroporation induced damage in the DNA of HL60 cells has been investigated by
      alkaline elution techniques. DNA damage is minimised by reducing the total charge
      applied (i.e., voltage x capacitance). Reduction of either of these electrical
      parameters, however, compromises the induced permeability of the cells to small
      molecules. The data presented concerning the effects of voltage and capacitance
      on DNA damage and the permeability of cells can be used to specify optimum
      conditions for electroporation in which DNA damage is minimised. The duration for
      which the current is applied can be seen to have a significant effect on the
      level of DNA damage. A modest temperature rise may occur when an electric charge
      is passed through electroporation buffer, but this event alone does not induce
      DNA damage in cells. The effect of voltage upon the permeability of HL60 cells to
      fluorescent-labelled molecules of varying molecular weight is reported.

PMID- 8547323
TI  - Cloning, sequence analysis and expression of mammalian mitochondrial protein
      synthesis elongation factor Tu.
AB  - The bovine liver mitochondrial protein synthesis elongation factor Tu.Ts complex
      (EF-TU.Tsmt) has been purified and partial peptide sequence information has been
      obtained for EF-Tumt. A complete cDNA has been obtained encoding bovine EF-Tumt
      and a nearly complete cDNA has been obtained for human EF-Tumt. The bovine cDNA
      has a 5' untranslated leader, an open reading frame of 1356 nucleotides and a 3'
      untranslated region of 189 base pairs. NH2-terminal sequencing of the mature
      protein indicates that the transit peptide for the mitochondrial localization of
      this protein is 43 amino acids in length. The human and bovine factors are 95%
      identical. The deduced protein sequences show considerable identity to bacterial
      and organellar EF-Tu sequences. At least two genes for EF-Tumt are present in the
      bovine system. Northern analysis indicates that EF-Tumt is synthesized in all
      tissues but that the level of expression varies over a wide range. EF-TUmt has
      been expressed in E. coli as a His-tagged protein and purified to near
      homogeneity. The expressed form of the factor is active in the poly(U)-directed
      polymerization of phenylalanine although it is less active than the native EF
      Tu.Tsmt complex.

PMID- 8547325
TI  - Transcription of interferon-alpha 2 alleles from virus-induced human leucocytes
      and lymphoblastoid cells of African origin.
AB  - It has been previously shown that the genomic DNA of both the lymphoblastoid cell
      line (Namalwa) and certain human donors (of African origin) contain sequences
      corresponding to two allelic variants, b and c, of the interferon-alpha 2 gene
      (IFNA2). Little is known however about the relative expression of these two
      alleles in heterozygous cells. We have therefore examined the transcription of
      allelic variants of the human IFNA2 locus by both normal human leucocytes (from a
      heterozygous donor) and Namalwa cells. Analysis of cDNA clones identified
      sequences of both allelic variants, IFNA2b and c, indicating active transcription
      by both cell types. Analysis of tryptic and peptic peptides derived from purified
      IFN-alpha 2 also demonstrated both IFN-alpha 2b and IFN-alpha 2c proteins.
      Populations of virus induced heterozygous cells can therefore effectively
      transcribe and secrete both forms of IFN-alpha 2 simultaneously, with no apparent
      restrictions on expression of either allele.

PMID- 8547326
TI  - Differences between nuclear run-off and mRNA levels for multidrug resistance gene
      expression in the cephalocaudal axis of the mouse intestine.
AB  - P-glycoprotein is a multidrug transporter encoded by the mdr3 gene in the mouse
      intestinal epithelium. The aims of this study were to characterize the mdr3 gene
      expression in the cephalocaudal axis of the intestine in adult animals and during
      perinatal development, and to define the molecular mechanism responsible for the
      heterogeneous expression of the gene along the cephalocaudal axis. RNA extracted
      from stomach, duodenum, jejunum, ileum, cecum and colon was hybridized by slot
      blot and Northern blot using a mdr3 cDNA probe. The regulation of gene expression
      was investigated examining the rate of transcription by nuclear run-off analysis.
      Transport studies of rhodamine 123, a substrate of P-glycoprotein, were performed
      in everted jejunum and ileum. The level of mdr3 mRNA and P-glycoprotein found in
      ileum was 6-fold higher than the level found in duodenum. The regional pattern of
      mdr3 gene expression is established in the intestine of 10-day-old animals.
      Similar mdr3 hybridization signal in nuclear run-off assay was found in nuclei of
      enterocytes isolated from jejunum and ileum, suggesting that the heterogeneous
      expression of the mdr3 gene in the cephalocaudal axis of the small bowel may be
      predominantly regulated at the post-transcriptional level. Transport rate of
      rhodamine 123 from the serosal to mucosal side in everted ileum was higher than
      the rate of transport found in jejunum. These results indicate that enterocytes
      of the ileum may be more actively involved in the P-glycoprotein-mediated
      transport of xenobiotics into the intestinal lumen.

PMID- 8547327
TI  - Mammalian mitochondrial DNA topoisomerase I preferentially relaxes supercoils in
      plasmids containing specific mitochondrial DNA sequences.
AB  - Selected regions of mammalian mitochondrial DNA (mtDNA) were inserted into pGEM
      plasmid vectors and used as substrates in a kinetic analysis of the highly
      purified bovine mitochondrial type I topoisomerase. Recombinant plasmids
      containing the bovine mtDNA heavy and light strand origins of replication (pZT
      Hori and pZT-Lori, respectively), a major transcription termination region (pZT
      Term) and a portion of cytochrome b gene (pZT-Cytb) were prepared. Southern
      hybridization using probes specific for either control or mtDNA-containing
      plasmid indicated a relative preference by the mitochondrial topoisomerase I to
      relax supercoils in pZT-Hori and pZT-Term. Quantitative determination of kinetic
      parameters derived from double-reciprocal Lineweaver-Burk plots showed that
      recombinant plasmids containing the heavy and light strand origins and the
      transcription termination region were preferentially relaxed by the mitochondrial
      enzyme with Km values 2.3- to 3.3-fold lower than controls. The Km values for pZT
      Hori, pZT-Lori and pZT-Term were 21.0 +/- 0.9 microM, 25.2 +/- 1.0 microM and
      17.0 +/- 0.8 microM, respectively, while those for control plasmids were 57.5 +/-
      2.1 microM and 56.3 +/- 2.3 microM. pZT-Cytb was not preferentially relaxed
      compared to the control plasmid (Km = 53.4 +/- 2.0 microM vs. 56.3 +/- 2.3
      microM, respectively) indicating that mitochondrial topoisomerase I
      preferentially interacts with certain mtDNA sequences but not others. Identical
      experiments with the purified nuclear enzyme did not differentiate between
      control or mtDNA containing plasmids.

PMID- 8547328
TI  - Characterization of human E4BP4, a phosphorylated bZIP factor.
AB  - In this report we described the isolation of transcription factor E4BP4 by lambda
      gt11 expression cloning using a probe containing the CRE/ATF-like sequence
      located between -2764 bp and -2753 bp in the upstream regulatory region for the
      human IL-1 beta gene. DNaseI protection, gel mobility shift analysis, and
      cotransfection studies were performed to investigate the binding and functional
      properties of E4BP4 using IL-1 beta promoter sequences. By DNaseI footprinting, a
      protection pattern was generated over the CRE/ATF-like site and the flanking
      sequences by bacterially produced E4BP4. Competition experiment by gel shift
      assay indicated that E4BP4 bound specifically to CRE/ATF-like site, not NF kappa
      B-like site. In cotransfection studies, E4BP4 repressed promoter activity and
      this repression was mediated through the CRE/ATF-like site. Mutational analysis
      of E4BP4 suggested that the DNA binding as well as repression activities required
      leucine heptad repeat domain. Analysis of E4BP4 produced in Escherichia coli and
      Sf9 cells infected with recombinant baculovirus indicated that baculovirus
      produced protein showed enhanced binding to the CRE/ATF-like site compared to the
      E. coli-produced protein. Analysis of posttranslational modifications indicated
      that E4BP4 produced in Sf9 cells was phosphorylated and this phosphorylation was
      important for the DNA binding activity of E4BP4.

PMID- 8547329
TI  - IAP retrotransposons in the mouse liver as reporters of ageing.
AB  - IAP are endogenous retrovirus-like elements present at a thousand copies in the
      murine genome. They can modulate the level of expression of the tagged genes into
      which they have inserted, and conversely their activity could be influenced by
      the level of activity of the genes and/or DNA sequences into which they are
      embedded. In this report, we have analysed by Northern blots the pattern of
      expression of the IAP-related transcripts in the organs of young and ageing mice.
      We show that IAP transcripts of unexpected size (namely 10 kb and 6 kb) are
      induced in the liver of ageing mice from all inbred and hybrid strains tested.
      These transcripts are not detected in young mice, and their intensity disclose
      variations depending on the strain, as those observed for the two canonical 7.2
      and 5.4 kb IAP transcripts. It is suggested that these age-dependent IAP
      transcripts originate from unique sites within the mouse genome that are 'tagged'
      by an IAP sequence, which would be sensitive both to strain-dependent cellular
      factors acting at the level of all IAPs, and to an age-dependent liver-specific
      cellular factor and/or DNA state, responsible for the position-dependent effect.
      These age-dependent transcripts should allow the identification of putative genes
      or factors of 'senescence'.

PMID- 8547330
TI  - The human insulin-like growth factor II leader 1 contains an internal ribosomal
      entry site.
AB  - Insulin-like growth factor II is a small peptide growth hormone, encoded by four
      mRNAs with unique 5' untranslated regions and identical coding regions. The 5'
      untranslated region transcribed from promoter 1 is 598 nt (leader 1). The
      properties of this leader 1 suggest a strong regulation of translation; the high
      G + C-content, the presence of an upstream open reading frame, and the length of
      the 5' UTR are 3 elements which prohibit efficient translation and which may
      modulate expression. In this paper we show that the human IGFII leader 1 harbours
      sequence elements that allow translation initiation to occur by internal
      initiation on the IGF sequence. This mode of initiation was described first for
      picornaviral mRNAs, that are naturally uncapped. The IGFII leader 1-dependent
      expression in HeLa cells was resistant to infection with poliovirus; abrogation
      of cap-dependent initiation by poliovirus had apparently no effect on IGFII
      expression. Moreover, a downstream CAT-cistron in a bicistronic construct was
      translated upon insertion of the leader 1 sequence. The translational properties
      of the IGFII leader 1 suggest that internal initiation on this leader may be
      modulated during proliferation or differentiation, enabling cell-stage dependent
      expression of IGFII.

PMID- 8547331
TI  - Conformation of Vespa basalis mastoparan-B in trifluoroethanol-containing aqueous
      solution.
AB  - Mastoparan-B, a tetradecapeptide isolated from the venom of the hornet Vespa
      basalis, belongs to the mastoparan analogs of vespid venom with the lysine
      residues common for all mastoparan family toxins at positions 4, 11 and 12. Here
      we use 1H-NMR spectroscopy and hybrid distance geometry-simulated annealing
      calculation to investigate its three-dimensional structure in trifluoroethanol
      containing aqueous solution. The calculated structure shows that residues 3-14
      adopt an amphiphilic alpha-helical structure in which the residues with
      hydrophilic side chains (i.e. Lys-4, Ser-5, Ser-8, Lys-11, Lys-12) are located on
      one side and the residues with hydrophobic side chains (i.e. Leu-3, Ile-6, Trp-9,
      Ala-10, Val-13, Leu-14) located on the other side of the molecule. The overall
      structural features a very similar to the conformation of mastoparan-X
      reconstituted in vesicle [Wakamatsu et al. (1992) Biochemistry 31, 5654-5660] in
      spite of the substitutions made for eight residues with distinctly different
      hydrophobicity. These substitutions lead to a larger hydrophobic moment for the
      alpha-helical segment and further mobilized N-terminal. This study will help
      reveal the conformational significance of mastoparan toxins with respect to their
      potency and activity in G protein regulation.

PMID- 8547332
TI  - Structure of the pseudosubstrate recognition site of chicken smooth muscle myosin
      light chain kinase.
AB  - The structure of the chicken smooth muscle myosin light chain kinase
      pseudosubstrate sequence MLCK(774-807)amide was studied using two-dimensional
      proton NMR spectroscopy. Resonance assignments were made with the aid of totally
      correlated and nuclear Overhauser effect spectroscopy. A distance geometry
      algorithm was used to process the body of NMR distance and angle data and the
      resulting family of structures was further refined using dynamic simulated
      annealing. The major structural features determined include two helical segments
      extending from Asp-777 to Lys-785 and from Arg-790/Met-791 to Trp-800 connected
      by a turn region from Leu-786 to Asp-789 enabling the helices to interact in
      solution. The C-terminal helix incorporates the bulk of the pseudosubstrate
      recognition site which is partially overlapped by the calmodulin binding site
      while the N-terminal helix forms the bulk of the connecting peptide. The
      demonstrated turn between the helices may assist in enabling the autoregulatory
      or pseudosubstrate recognition sequence to be rotated out of the active site of
      the catalytic core following calmodulin binding.

PMID- 8547333
TI  - Transcobalamin from cow milk: isolation and physico-chemical properties.
AB  - The concentration of endogenous cobalamin (Cbl) in cow milk was 3.3 nM while the
      Cbl-binding capacity was 0.05 nM. Both endogenous and newly added Cbl showed
      similar quantitative distribution between a 280 kDa protein complex (45%) and a
      43 kDa Cbl-binder (55%). Long time incubation, as well as urea treatment, was
      accompanied by a slow release of the 43 kDa Cbl-binder from the 280 kDa fraction.
      No other Cbl-binding proteins appeared after these procedures. The 43 kDa binder
      from cow milk, depleted of the ligand by urea treatment, reacted with Cbl even in
      the presence of a B12-analogue cobinamide (Cbi) at the ratio Cbl:Cbi = 1:40. The
      stokes radius of the binder changed from 2.7 nm for the Cbl-free protein to 2.5
      nm for the Cbl-saturated form and the Cbl-saturated binder was able to displace
      human transcobalamin (TC) from the TC-receptor. The interaction between the
      protein and Cbl was significantly suppressed at pH 2.0. The N-terminal sequence
      of the purified 43 kDa Cbl-binder revealed homology with TC from human and rabbit
      plasma. In conclusion we have shown that TC is the main Cbl-binding protein in
      cow milk. This is surprising, since previous studies on human and rat milk have
      shown another Cbl-binder, apo-haptocorrin, to be the dominating Cbl-binding
      protein.

PMID- 8547334
TI  - Delta 6-desaturase: improved methodology and analysis of the kinetics in a multi
      enzyme system.
AB  - A new method of assay for the delta 6-desaturation of linoleic acid was
      developed. This method, which uses HPLC for separation of the fatty acid
      substrate and product, exhibited a lower coefficient of variation (0.3%) than the
      reported TLC method (3.5%), and avoided the step of methylation of the saponified
      fatty acid substrate and product. Using this new method of assay, the kinetics of
      the delta 6-desaturase in a multi-enzyme system were analysed. A number of
      factors that could have striking effects on desaturase kinetics were
      investigated, including the effect of (i) endogenous microsomal linoleic acid on
      total substrate concentration, and (ii) the pre-reaction catalysed by acyl-CoA
      synthetase and competing reactions catalysed by lysophospholipid acyltransferase
      and acyl-CoA hydrolase. Endogenous free linoleate in the hepatic microsomes was
      found to be 2.9 +/- 1.0 microM (0.5 mg microsomal protein/ml), which was
      comparable to added substrate concentrations (1.8 to 7.9 microM). The kinetics of
      the delta 6-desaturase were dissected from the kinetics of the above mentioned
      pre-reaction and competing reactions through a combination of experimental
      approaches and computer modeling. From computer modeling, a Km and Vmax of 1.5
      microM and 0.63 nmol/min were calculated for the delta 6-desaturase, compared to
      Km and Vmax of 10.7 microM and 0.08 nmol/min calculated directly from data
      uncorrected for endogenous substrate. It was concluded that lysophospholipid
      acyltransferase, acyl-CoA synthetase and endogenous linoleic acid significantly
      affect the kinetic measurements of hepatic microsomal delta 6-desaturase. These
      results have implications for kinetic analyses of all desaturates in microsomal
      systems.

PMID- 8547335
TI  - Spectroscopical and functional characterization of the hemoglobin of Nostoc
      commune (UTEX 584 (Cyanobacterial).
AB  - Structural analysis of a monomeric hemoglobin from the cyanobacterium Nostoc
      commune strain UTEX 584, cyanoglobin (Potts et al. (1992) Science 256, 1690
      1692), is presented. Cyanoglobin binds molecular oxygen reversibly, with high
      oxygen affinity and non-cooperativity. There was no evidence for decreased
      stability of the pigment at 37 degrees C. Cyanoglobin-specific antibodies showed
      no cross-reactivity with two reference hemoglobins, leghemoglobin a and sperm
      whale myoglobin. The absorption spectral properties of cyanoglobin differ
      significantly from those of the two reference hemoglobins. The spectrum of oxy
      cyanoglobin most closely resembles that of an oxy-hemoglobin from the protozoan
      Tetrahymena pyriformis, a hemoprotein that shares substantial amino-acid sequence
      identity with cyanoglobin. Met-cyanoglobin possesses spectral characteristics at
      pH 7.0-9.0 that resemble those of the alkaline met-hemoglobin (a putative
      hemichrome) of another protozoan, Paramecium caudatum. The spin-state character
      of met-cyanoglobin is pH-dependent. Met-cyanoglobin does not coordinate the
      strong-field ligands, cyanide and azide, at pH 7.0. The capacity of cyanoglobin
      to coordinate cyanide increased with decreasing pH. Far-UV CD spectra of
      cyanoglobin are indicative of a protein with a significant amount of alpha
      helical structure. Data from Soret-region CD spectra suggest that the
      orientations of the heme moieties in cyanoglobin and leghemoglobin a are similar
      to one another.

PMID- 8547336
TI  - Total reconstitution of active small ribosomal subunits of the extreme halophilic
      archaeon Haloferax mediterranei.
AB  - The small ribosomal subunit of the halophilic archaeon Haloferax mediterranei has
      been reconstituted from its dissociated rRNA and protein components. Efficient
      reconstitution of particles, fully active in poly(U)-dependent polyphenylalanine
      synthesis, occurs after 2 h of incubation at 36 degrees C in the presence of 1.5
      M of (NH4)2SO4, 100 mM of MgAc2, 20 mM Tris-HCl (pH 8.2) and 6 mM 2
      mercaptoethanol. Important differences in the optimal ionic conditions for the
      reconstitution of the 30S and the 50S ribosomal subunits from Haloferax
      mediterranei have been found. K+ and NH4+ ions have differing abilities to
      promote the reconstitution of the particles. The assembly of 30S ribosomal
      subunits of H. mediterranei has a higher tolerance to ionic strength than the
      assembly of the 50S subunits and it is independent of the Mg2+ concentration
      present in the system.

PMID- 8547337
TI  - Determination of three-dimensional solution structure of waglerin I, a toxin from
      Trimeresurus wagleri, using 2D-NMR and molecular dynamics simulation.
AB  - The solution conformation of a synthetic snake venom toxin waglerin I, has been
      determined by using proton nuclear magnetic resonance spectroscopy. By a
      combination of various two-dimensional NMR techniques, the 1H-NMR spectrum of
      waglerin I was completely assigned. A set of 247 interproton distance restraints
      was derived from nuclear Overhauser enhancement (NOE) measurements. These NOE
      constraints, in addition to the 2 dihedral angle restraints (from coupling
      constant measurements) and 7 omega torsion angel restraints for prolines, formed
      the basis of three-dimensional structure determined by molecular dynamics
      techniques. The 19 structures that were obtained satisfy the experimental
      restraints, and display small deviation from idealized covalent geometry.
      Analysis of converged structures indicates that the toxin has no special
      secondary structure. In the solution structure of waglerin I, the central ring
      region is well defined but the N- and C-termini possesses more disorder.

PMID- 8547338
TI  - In vivo endoproteolytically cleaved phaseolin is stable and accumulates in
      developing Phaseolus lunatus L. seeds.
AB  - Phaseolin is the most abundant storage protein of bean seeds. To modify its amino
      acidic composition by protein engineering, for the improvement of its nutritional
      value, regions which could be modified without detrimental effects on structural
      features of the protein must be identified. Data presented here, on the
      characterisation of the major storage protein of lima bean (Phaseolus lunatus L.)
      seeds, a phaseolin-like glycoprotein, provide good indications on one of such
      region. Phaseolus lunatus phaseolin consists of four major oligomers containing
      two subunit classes. Polypeptides of one class show a molecular mass ranging from
      38.5 kDa to 32 kDa, while the molecular mass of polypeptides belonging to the
      other class ranges from 27 kDa to 21 kDa. The subunits originate from the
      cleavage of precursor forms, with molecular masses of 58 kDa and 54 kDa, which
      are still present - in residual amounts - in the nature protein. Comparison of
      their N-terminal sequences with those of the subunits demonstrate that cleavage
      occurs in a region of the molecule that instead remains uncleaved in phaseolins
      of the other species. Since this region can accommodate such a drastic
      modification, we suggest it could be a good candidate for in vitro manipulation.

PMID- 8547339
TI  - Mouse coproporphyrinogen oxidase is a copper-containing enzyme: expression in
      Escherichia coli and site-directed mutagenesis.
AB  - We previously isolated cDNA for mouse coproporphyrinogen oxidase (CPO) and
      provided evidence for the induction of mRNA during differentiation of murine
      erythroleukemia cells (Kohno et al. (1993) J. Biol. Chem. 268, 21359-21363). To
      better understand the structure and the mechanisms of reaction of the enzyme, we
      expressed mouse CPO in Escherichia. coli and purified it to a homogeneity.
      Analysis of the metal content revealed that the recombinant mouse CPO contains
      one copper atom per polypeptide chain. When the bacterial cells were treated with
      D-penicillamine, a copper chelator, formation of the active CPO was partially
      reduced. Addition of Cu2+ in minimal medium resulted in 6-fold higher level of
      CPO activity. These results suggest that expression of active mouse CPO in E.
      coli depended on the presence of Cu2+ in the culture medium. To elucidate the
      apparent involvement of Cu2+ in enzyme function, a series of mutant enzymes,
      whose highly conserved histidine and cysteine residues were individually
      converted to alanine residue, were prepared by site-directed mutagenesis. Mutant
      enzymes were expressed in E. coli and their activities examined. Mutation at
      histidine 158 resulted in a complete loss of enzyme activity, yet the enzyme
      protein was expressed at a comparable level. Concomitantly, only a trace amount
      of Cu2+ was detected in the purified H158A enzyme. We propose that mouse CPO is
      copper-containing enzyme and Cu2+ interacts with a conserved histidine residue.

PMID- 8547340
TI  - Relationship between kinetic properties of gamma-glutamyl transpeptidase and the
      structure of its saccharide moiety.
AB  - Gamma-glutamyl transpeptidase (EC 2.3.2.2; GGT) is a plasma-membrane bound
      glycoenzyme, the saccharide moiety of which is rather heterogeneous and organ
      specific. It has been stated that GGT catalyses three types of reactions, i.e.,
      hydrolysis, transpeptidation and autotranspeptidation. The initial velocity
      equation, involving all these reactions, is shown in the present report.
      Mathematical analysis of the equation resulting in a definition of the constant
      of half saturation (Khs). The value of Khs was used for characterization of
      kinetics of GGT from rat organs differing in the structure of GGT oligosaccharide
      chains. No significant organ differences were found, when the Khs values of GGT
      from the brain, kidney and pancreas equalled 0.61 mM, 0.68 mM and 0.68,
      respectively. On the contrary, when two different glycoforms of GGT from the
      pancreas were compared, distinct values of Khs were obtained (1.43 mM and 0.67
      mM, respectively). It is therefore being suggested that the saccharide chains of
      GGT are involved in its kinetic properties. However, this effect is masked when
      the enzyme, non-fractionated into glycoforms, is analysed, even though the
      saccharide moiety is specific for the organ studied.

PMID- 8547341
TI  - Isolation and structural characterization of recombinant human neu
      differentiation factor expressed in Escherichia coli.
AB  - Recombinant human neu differentiation factor produced in engineered E. coli was
      isolated and subject to structural characterization. The recombinant molecule can
      be prepared to apparent purity and is active in stimulating receptor tyrosine
      autophosphorylation in cultural cells expressing HER2 receptor. The 229 amino
      acid polypeptide consists of eight cysteines, of which two cysteines near the N
      terminus are disulfide-bonded to form an immunoglobulin-like domain and the
      remaining six cysteines at the C-terminus cross-link to form an epidermal growth
      factor-like structure. Detailed chemical characterization of the recombinant
      molecule by peptide mapping in conjunction with Edman sequencing and mass
      spectrometry reveals that the bacterially produced recombinant neu
      differentiation factor preparation is properly folded and contains the correct
      disulfide structure. The peptide mapping procedure is also useful in identifying
      abnormal peptides derived from deamidation and oxidation of Asn and Met residues,
      respectively.

PMID- 8547342
TI  - Evidence for a posttranslational covalent modification of liver glyceraldehyde-3
      phosphate dehydrogenase in hibernating jerboa (Jaculus orientalis).
AB  - The specific activity of D-glyceraldehyde-3-phosphate (G3P) dehydrogenase
      (phosphorylating) (GPDH, EC 1.2.1.12) found in liver of induced hibernating
      jerboa (Jaculus orientalis) was 2-3-fold lower than in the euthermic animal.
      However, the comparative analysis of the soluble protein fraction of these
      tissues by SDS-PAGE and Western blotting showed no significant changes in the
      intensity of the 36 kDa protein band of the GPDH subunit. After using the same
      purification procedure, the GPDH from liver hibernating jerboa exhibited lower
      values for both apparent optimal temperature and specific activity than the
      enzyme from the euthermic animal. Similar non-linear Arrhenius plots were
      obtained, but the Ea values calculated for the GPDH from hibernating tissue were
      higher. Although in both purified enzyme preparations four isoelectric GPDH
      isoforms were resolved by chromatofocusing, those of hibernating liver exhibited
      more acidic pI values (pI 7.3-6.1) than the hepatic isoforms of euthermic animals
      (pI 8.7-8.1). However, all liver GPDH isoforms exhibited similar native and
      subunit molecular masses and cross-reacted with an antibody raised against muscle
      GPDH. The comparison of the kinetic parameters of both purified preparations and
      the main isoforms isolated from euthermic and hibernating tissues showed the
      decreased catalytic efficiency of hibernating enzyme being exclusively due to a
      lower Vmax for both substrates G3P and NAD+. Phosphodiesterase treatment of cell
      free extracts increased GPDH activity in the case of hibernating liver only. The
      pI of the main isoform purified from this tissue, about 6.9, changed after this
      treatment to an alkaline value (pI 8.44) similar to those of the euthermic GPDH
      isoforms. Differential ultraviolet absorption spectra of these isoforms indicated
      that a substance absorbing at 260 nm, that was released by the phosphodiesterase
      digestion, was present in the enzyme of hibernating tissue. Incubation of
      purified GPDH with the NO-releasing agent sodium nitroprussite produced under
      conditions that promote mono-ADP-ribosylation a dramatic decrease of activity (up
      to 60%) of both euthermic and phosphodiesterase-treated hibernating preparations
      but only a marginal inhibition of the hibernating enzyme. These data suggest that
      the liver GPDH of hibernating jerboa exhibits a posttranslational covalent
      modification, being probably a mono-ADP-ribosylation. The resulting inhibition of
      enzyme activity could contribute to the wide depression of the glycolytic
      metabolic flow associated with mammalian hibernation.

PMID- 8547343
TI  - Trypanosoma cruzi phospho enol pyruvate carboxykinase (ATP-dependent): transition
      metal ion requirement for activity and sulfhydryl group reactivity.
AB  - We studied the transition metal ion requirements for activity and sulfhydryl
      group reactivity in phospho enol pyruvate carboxykinase (PEP-carboxykinase;
      ATP:oxaloacetate carboxylase (transphosphorylating), EC 4.1.1.49), a key enzyme
      in the energy metabolism of the protozan parasite Trypanosoma (Schizotrypanum)
      cruzi. As for other PEP-carboxykinases this enzyme has a strict requirement of
      transition metal ions for activity, even in the presence of excess Mg2+ ions for
      the carboxylation reaction; the order of effectiveness of these ions as enzyme
      activators was: Co2+ > Mn2+ > Cd2+ > Ni2+ >> Fe2+ > VO2+, while Zn2+ and Ca2+ had
      no activating effects. When we investigated the effect of the varying type or
      concentration of the transition metal ions on the kinetic parameters of the
      enzyme the results suggested that the stimulatory effects of the transition metal
      center were mostly associated with the activation of the relatively inert CO2
      substrate. The inhibitory effects of 3-mercaptopicolinic acid (3MP) on the enzyme
      were found to depend on the transition metal ion activator: for the Mn(2+)
      activated enzyme the inhibition was purely non-competitive (Kii = Kis) towards
      all substrates, while for the Co(2+)-activated enzyme the inhibitor was much less
      effective, produced a mixed-type inhibition and affected differentially the
      interaction of the enzyme with its substrates. The modification of a single,
      highly reactive, cysteine per enzyme molecule by 5,5'-dithiobis (2-nitro
      benzoate) (DTNB) lead ton an almost complete inhibition of Mn(2+)-activated T.
      cruzi PEP-carboxykinase; however, in contrast with the results of previous
      studies in vertebrate and yeast enzymes, the substrate ADP slowed the chemical
      modification and enzyme inactivation but did not prevent it. PEP and HCO3- had no
      significant effect on the rate or extent of the enzyme inactivation. The kinetics
      of the enzyme inactivation by DTNB was also dependent on the transition metal
      activator, being much slower for the Co(2+)-activated enzyme than for its Mn(2+)
      activated counterpart. When the bulkier but more hydrophobic reagent N-(7
      dimethylamino-4-methylcoumarinyl)maleimide (DACM) was used the enzyme was slowly
      and incompletely inactivated in the presence of Mn2+ and ADP afforded almost
      complete protection from inactivation; in the presence of Co2+ the enzyme was
      completely resistant to inactivation. Taken together, our results indicate that
      the parasite enzyme has a specific requirement of transition metal ions for
      activity and that they modulate the reactivity of a single, essential thiol
      group, different from the hyperreactive cysteines present in vertebrate or yeast
      enzymes.

PMID- 8547344
TI  - Properties and stabilization of an extracellular alpha-glucosidase from the
      extremely thermophilic archaebacteria Thermococcus strain AN1: enzyme activity at
      130 degrees C.
AB  - An extracellular alpha-glucosidase from the thermophilic archaebacterium
      Thermococcus strain AN1 was purified 875-fold in five steps (Hiload Q-Sepharose,
      phenyl Sepharose, HPHT-hydroxyapatite, gel filtration and Mono Q chromatography)
      with a yield of 4%. It is a monomer with a molecular mass of about 60 kDa and a
      pI around 5. At 98 degrees C, the purified enzyme in buffer has a half-life
      around 35 min, which is increased to around 215 min in presence of 1% (w/v)
      dithiothreitol and 1% (w/v) BSA. Dithiothreitol (1%, w/v) and BSA (0.4%, w/v)
      also substantially increase the enzyme activity. The Km at 75 degrees C is 0.41
      mM with pNP-alpha-D-glucopyranoside as substrate. The substrate preference of the
      enzyme is: pNP-alpha-D-glucoside > nigerose > panose > palatinose > isomaltose >
      maltose and turanose. No activity was found against starch, pullulan, amylose,
      maltotriose, maltotetraose, isomaltotriose, cellobiose and beta-gentiobiose. A
      variety of techniques including immobolization (e.g., on epoxy and glass beads),
      chemical modification (cross- and cocross-linking) and the use of additives
      (including polyhydroxylic molecules, BSA, salts, etc.) were applied to enhance
      stability at temperatures above 100 degrees C. The half-life could be increased
      from about 4 min at 100 degrees C to 30-60 min at 130 degrees C in presence of
      90% (w/v) sorbitol, 1% (w/v) dithiothreitol and 1% (w/v) BSA, and by cross
      linking with BSA in the presence of 90% (w/v) sorbitol. The stabilized enzyme
      showed good activity at 130 degrees C.

PMID- 8547346
TI  - Synthesis and structural characterisation of analogues of the potassium channel
      blocker charybdotoxin.
AB  - Charybdotoxin is a 37-residue polypeptide toxin from scorpion venom, which acts
      by blocking voltage-gated and Ca(2+)-activated K+ channels. We have synthesized
      charybdotoxin and three mono-substituted analogues using an Fmoc-tBu protocol.
      The Phe-2 --> Tyr analogues was chosen to introduce a site for Tyr iodination
      which was distinct from the K+ channel binding surface, while the Glu-12 --> Gln
      and Arg-19 --> His analogues were studied to probe the roles of charged residues
      at these positions in the structure and activity of the toxin. The synthetic
      native molecule was equipped with natural toxin in inhibiting the human
      erythrocyte Ca(2+)-dependent K+ channel. The affinities of all three analogues
      for the erythrocyte K+ channel were slightly reduced, with the Arg-19 --> His
      analogue showing the greatest increase in IC50 (2.30-fold). Two-dimensional 1H
      NMR studies of these analogues showed that the Glu-12 to Gln substitution, which
      appeared to destabilise the N-terminal half of the alpha-helix, possibly due to
      the weakening of an N-terminal helix capping interaction which is apparent from
      our NMR data. His-21 has a pKa more than one unit below the value for a non
      interacting histidine. Possible reasons for this are that the imidazolium side
      chain is partly buried and is located near positively charged moieties. Thus, His
      21 would be neutral at physiological pH, where charybdotoxin binds to the
      potassium channel.

PMID- 8547345
TI  - Purification and characterization of folate binding proteins from rat placenta.
AB  - Rat placenta contains virtually no unsaturated (i.e., apo-form) folate binding
      protein. However, by lowering the pH of a solubilized membrane preparation of
      this tissue to 3.5, the endogenous bound folate was dissociated from the protein
      and adsorbed to charcoal. The apo-form of the folate binding protein thus
      obtained was purified by affinity chromatography using pteroylglutamic acid
      covalently coupled to Sepharose 4B. A single protein band with an apparent M(r)
      of 36,000 was observed by SDS-polyacrylamide gel electrophoresis of the eluate
      from the affinity matrix. Western blot of this preparation using a rabbit
      antiserum raised with the affinity eluate also identified a single 36 kDa protein
      band. However, peptide sequencing of the N-terminal region of the proteins in the
      affinity eluate established that it contained two homologous proteins. Computer
      alignment of the first 22 N-terminal amino acids of each rat placental protein
      with human, bovine milk and mouse folate binding proteins showed 50-64% identical
      homology and 27% homology when the eight proteins were aligned together. The
      affinity of both rat proteins is highest for pteroylglutamic acid (Ka = 1.6.10(9)
      l/mol) lower for N5-methyltetrahydrofolate and substantially lower for N5
      formyltetrahydrofolate. In the dose-response range studied there was no apparent
      affinity for methotrexate. The folate binding proteins could be released from a
      preparation of placental membranes using phospholipase C indicating that these
      proteins belong to the class of proteins anchored to the plasma membrane by a
      glycosyl phosphatidylinositol adduct.

PMID- 8547347
TI  - Spectroscopic characterization of nitrosylheme in nitric oxide complexes of
      ferric and ferrous cytochrome c' from photosynthetic bacteria.
AB  - Reactions of ferric and ferrous cytochromes c' from four photosynthetic bacteria
      (Rhodobacter capsulatus ATCC 11166, Rhodopseudomonas palustris ATCC 17001,
      Rhodospirillum rubrum ATCC 11170, and Chromatium vinosum ATCC 17899) with nitric
      oxide have been investigated by electronic absorption and electron paramagnetic
      resonance spectroscopies. The heme iron(III) of these ferric cytochromes c' has
      been recently reported to be in a quantum mechanically admixed (S = 5/2, 3/2)
      state [Fujii, S., Yoshimura, T., Kamada, H., Yamaguchi, K., Suzuki, S., Shidara,
      S. and Takakuwa, S. (1995) Biochim. Biophys. Acta 1251, 161-169]. The affinity of
      ferric cytochromes c' for NO among these bacterial species (C. vinosum > Rps.
      palustris approximately Rb. capsulatus >> R. rubrum) was apparently related to
      the S = 3/2 content in the or der. In the reaction of ferrous cytochrome c' with
      NO, six- and five-coordinated nitrosylhemes, which represent species with and
      without a ligand at the axial position trans to nitrosyl group, have been formed.
      The content of six-coordinated nitrosylheme in NO-ferrous cytochrome c' has been
      determined to be Rb. capsulatus approximately Rps. palustris > C. vinosum < R
      rubrum, suggesting that a stability of iron-to-histidine bond decreases with this
      order. The NO reactions of ferric and ferrous cytochromes c' from photosynthetic
      bacteria have been compared with those of cytochromes c' from denitrifying
      bacteria.

PMID- 8547348
TI  - Determination of the structural role of the N-terminal domain of human
      extracellular superoxide dismutase by use of protein fusions.
AB  - The N-terminal domain, containing the 49 N-terminal amino-acid residues, of human
      extracellular superoxide dismutase (hEC-SOD) has been studied after construction
      of fusion proteins comprised of the defined domain and human carbonic anhydrase
      II (HCAII). The specific advantage of this technique is that it allows
      characterization of properties that are intrinsic to the N-terminal domain of hEC
      SOD, i.e., the results are not obscured by properties pertaining to the rest of
      the hEC-SOD molecule. Moreover, the fusion to HCAII allows a rapid and gentle one
      step purification by affinity chromatography. When the N-terminal domain was
      fused to the N-terminal of HCAII ( = FusNN) a well defined structure was formed
      and the resulting protein was tetrameric. When the same hEC-SOD-derived domain
      was fused to the C-terminal of HCAII ( = FusNC), no defined structure of the
      fused domain could be observed, and the resulting protein was monomeric. It was
      concluded that a 'free' N-terminus is required for formation of the proper
      structure of the N-terminal domain.

PMID- 8547349
TI  - Acidic amino acid-rich sequences as binding sites of osteonectin to
      hydroxyapatite crystals.
AB  - Osteonectin, an acidic noncollagenous protein of bone and dentin, has affinity to
      hydroxyapatite crystals. Binding sites to hydroxyapatite of this protein were
      determined by a proteolytic experiment and an in vitro binding experiment using
      synthetic peptide analogues. Osteonectin was adsorbed on hydroxyapatite crystals
      and digested with trypsin. A peptide was left adsorbed on the crystal even after
      the digestion. The peptide was identified as an amino terminal peptide containing
      glutamic acid-rich sequences, which have been assumed to be possible
      hydroxyapatite-binding sites. Poly glutamic acid sequences were synthesized as
      models of the binding sites. Glu6 peptide was bound to the hydroxyapatite with a
      dissociation constant of 2.4 microM. Peptides containing fewer glutamic acids had
      lower affinity to the crystal. Effects of these peptides on in vitro
      mineralization were examined by a gel system in microtiter plates. The Glu6
      peptide had a positive effect on the mineralization in this system, whereas Asp6
      peptide had a negative effect. These effects indicate the presence of an
      interaction between these peptides and mineral crystals.

PMID- 8547350
TI  - Pressure-induced inactivation of E. coli beta-galactosidase: influence of pH and
      temperature.
AB  - In order to assess the feasibility of a high-pressure immunodesorption process
      using a beta-galactosidase-anti-beta-galactosidase complex as a model, the
      influence of high hydrostatic pressure on the activation of E. coli beta
      galactosidase has been investigated. The irreversible activity loss of beta
      galactosidase was studied as a function of pH and temperature for pressures
      comprised between atmospheric pressure and 500 megapascal (MPa; 1 MPa = 10 bar).
      This enabled us to establish a practical pressure-temperature diagram of
      stability for this enzyme. The stability domains determined thus appeared to be
      strongly dependent on the pH under atmospheric pressure of phosphate buffer
      employed for pressurisation. Therefore, to interpret meaningfully this result,
      the influence of pressure on the pH-activity curve of beta-galactosidase was
      investigated by using a high-pressure stopped-flow device. It appeared that the
      pH-activity curve of this enzyme was also reversibly affected by pressures lower
      than 150 MPa. An interpretation of these results in relation to the high-pressure
      induced changes of ionisation constants is proposed. For our practical purpose,
      the implications for the elaboration of a high-pressure immunodesorption process
      using beta-galactosidase as a tag, are discussed.

PMID- 8547351
TI  - Enhanced susceptibility to transglutaminase reaction of alpha-lactalbumin in the
      molten globule state.
AB  - The susceptibility of alpha-lactalbumin to transglutaminase reactions was studied
      using an enzyme from Streptoverticillium which can catalyze the reactions
      irrespective of the presence or absence of Ca2+. Transglutaminase-catalyzed
      polymerization of alpha-lactalbumin in the native state occurred to a very
      limited extent. Transformation from the native state to the molten globule state
      brought about by Ca(2+)-removal from holo-alpha-lactalbumin enhanced the
      polymerization of the protein catalyzed by transglutaminase. The incorporation of
      Carbobenzoxy-Gln-Gly into alpha-lactalbumin through the enzyme reaction was
      investigated to determine the amounts of lysine residues which are present at
      molecular surface and available to the enzyme. There was no significant
      difference in the amount of available lysine residues between the native and the
      molten globule molecule. However, the amount of surface glutamine residues
      incorporated with monodansylcadaverine by transglutaminase was remarkably higher
      in the molten globule state than that in the native state. The
      monodansylcadaverine-incorporated site of alpha-lactalbumin in the molten globule
      state was identified as Gln-54 by amino-acid sequence analysis of fluorescence
      labeled peptides separated from chymotryptic digests of the protein. Possible
      reason for selective labeling of Gln-54 in molten globule alpha-lactalbumin was
      proposed.

PMID- 8547352
TI  - Nucleotide binding to tubulin-investigations by nuclear magnetic resonance
      spectroscopy.
AB  - In an attempt to distinguish between the interaction of GTP and ATP with tubulin
      dimer, high-resolution 1H- and 31P-NMR experiments have been carried out on the
      nucleotides in the presence of tubulin. The location of the ATP binding sites on
      the protein in relation to the GTP sites is still not clear. Using NMR
      spectroscopy, we have tried to address this question. Evidence for the existence
      of a site labelled as X-site and another site (labelled as L-site) for both the
      nucleotides on tubulin has been obtained. It is suggested that this X-site is
      possibly the putative E-site. In order to gain further insight into the nature of
      these sites, the Mg(II) at the N-site has been replaced by Mn(II) and the
      paramagnetic effect of Mn(II) on the linewidth of the proton resonances of
      tubulin-bound ATP and GTP has been studied. The results show that the L-site
      nucleotide is closer to the N-site metal ion compared to the X-site nucleotide.
      On the basis of these results, it is suggested that the L-site of ATP is distinct
      from the L-site of GTP while the X-site of both the nucleotides seems to be same.
      By using the paramagnetic effect of the metal ion, Mn(II), at the N-site on the
      relaxation rates of tubulin-bound ATP at L-site, distances of the protons of the
      base, sugar and phosphorous nuclei of the phosphorous moiety of ATP, from the N
      site metal ion have been mapped. The base protons are approximately equal to 0.8
      1 nm from this metal ion site. On the other hand, the phosphorous nuclei of the
      phosphate groups are somewhat nearer (approximately equal to 0.4-0.5 nm) from the
      N-site metal ion.

PMID- 8547353
TI  - Engineering the C-terminus of firefly luciferase as an indicator of covalent
      modification of proteins.
AB  - Protein kinase recognition sequences and proteinase sites were engineered into
      the cDNA encoding firefly luciferase from Photinus pyralis in order to establish
      whether these modified proteins could be developed as bioluminescent indicators
      of covalent modification of proteins. Two key domains of the luciferase were
      modified in order to identify regions of the protein in which peptide sequences
      may be engineered whilst retaining bioluminescent activity; one between amino
      acids 209 and 227 and the other at the C-terminus, between amino acids 537 and
      550. Mutation of amino acids between residues 209 and 227 reduced bioluminescent
      activity to less than 1% of wild-type recombinant. In contrast engineering
      peptide sequences at the C-terminus resulted in specific activities ranging from
      0.06-120% of the wild-type recombinant. Addition of cyclic AMP dependent protein
      kinase catalytic subunit, to a variant luciferase incorporating the kinase
      recognition sequence, LRRASLG, with a serine at amino-acid position 543 resulted
      in a 30% reduction in activity. Alkaline phosphatase treatment restored activity.
      The bioluminescent activity of a variant luciferase containing a thrombin
      recognition sequence, LVPRES, with the cleavage site positioned between amino
      acid 542 and 543, decreased by 50% when incubated in the presence of thrombin.
      The results indicate regions within luciferase where peptide sequences may be
      engineered while retaining bioluminescent activity and have shown changes in
      bioluminescent activity when these sites are subjected to covalent modification.
      Changes in secondary structure, charge and length at the C-terminus of luciferase
      disrupt the microenvironment of the active site, leading to alterations in light
      emission. This has important implications both in understanding the evolution of
      beetle bioluminescence and also in development of bioluminescent indicators of
      the covalent modification of proteins.

PMID- 8547354
TI  - Binding and aggregation of human mu-calpain by terbium ion.
AB  - Human mu-calpain is activated maximally by 100-200 microM Ca2+. Both the 80 kDa
      and 29 kDa subunits of mu-calpain have a EF-hand type calcium-binding domain. It
      is known that trivalent terbium ion (Tb3+) mimics Ca2+ in many biological
      systems. We found that Tb3+ alone transiently activated calpain. However, in the
      presence of Ca2+, Tb3+ inhibited mu-calpain with an IC50 of about 100 microM. As
      high as 10 mM Ca2+ did not significantly shift the IC50 of Tb3+. Preincubating mu
      calpain by Ca2+ (before Tb3+ and substrate were added) did not diminish the
      inhibition by Tb3+. On the other hand, pretreating mu-calpain with Tb3+ produced
      that Tb3+ has a slow dissociation rate for the calcium-binding sites when
      compared to Ca2+. Electrophoretic analysis revealed that terbium ion transiently
      activated mu-calpain followed by the aggregation of the proteinase.

PMID- 8547355
TI  - Electrophoretic pattern of cytosolic pyruvate kinase fractions A and B (type L
      and M2) from normal rat liver and Morris hepatoma 7777.
AB  - Cytosolic pyruvate kinase fractions A and B obtained by salting out procedure
      from normal rat liver and Morris hepatoma 7777, purified by affinity
      chromatography on Blue Sepharose CL-6B, have shown similar electrophoretic
      patterns in polyacrylamide gel at pH 8.3 to previously studied pyruvate kinase
      extracts from chromatin of cell nuclei. Three variants (alpha 1, beta 1, gamma 1)
      from normal rat liver pyruvate kinase fraction A (type L) had the greatest
      electrophoretic mobility, showed sigmoidal kinetics in relation to 2
      phosphoenolpyruvate (PEP), and sensitivity to ATP and fructose 1,6-diphosphate
      (FDP). The fraction A dominated over normal liver fraction B (type M2), which in
      electrophoresis showed a slower gamma 2 variant, similar to the fraction A of
      hepatoma. All variants from fractions B of normal liver and A of hepatoma had
      linear kinetics and were sensitive to ATP but not to FDP. The greatest
      differences showed pyruvate kinase fraction B from Morris hepatoma. Its all
      variants alpha 2, beta 2, gamma 3 were cathodic and had linear kinetics in
      relation to PEP. They all were insensitive to normal signal molecules (ATP and
      FDP). The gamma 3 alkaline variant acquired sensitivity to inhibition by L
      cysteine. Showing several-fold higher activity, much greater affinity to the main
      substrate, and a lack of sensitivity to feed-back inhibition by ATP, it was
      responsible for a high rate of aerobic glycolysis and diminution of the Pasteur
      effect in metabolic studies. It was probably encoded during oncogene activation
      and plays a special role in different metabolic strategies of tumour cells.

PMID- 8547356
TI  - HIV antibody testing of gay men in smaller US cities.
AB  - The incidence of new AIDS diagnoses among gay males indicates that risk reduction
      in smaller communities may be lagging behind that reported in larger cities.
      Contradictory evidence exists, largely from urban areas, concerning the utility
      of HIV testing as a means of promoting behavioural change. This study examined
      the relationship between HIV antibody testing and subsequent high-risk sexual
      behaviours among gay men in cities of 180,000 or fewer inhabitants. In February
      and March of 1992, male gay bar patrons in sixteen small US cities were
      administered an anonymous questionnaire concerning recent sexual behaviour and
      HIV testing history. Of the 1820 respondents, 28.1% had recently engaged in
      unprotected anal intercourse and 60.7% had been tested for HIV antibodies. Those
      who had been tested were more sexually active and reported more protected and
      safer sexual activities. Analyses at the individual and city levels converged to
      demonstrate that communities as well as individuals evidence increased self
      protection in association with HIV antibody testing.

PMID- 8547357
TI  - Factors associated with Hispanic women's HIV-related communication and condom use
      with male partners.
AB  - To determine factors influencing Hispanic women's HIV-related communication and
      condom use with their primary male partner, 189 Dominican, Puerto Rican, and
      Mexican women were interviewed regarding sexual behaviour and condom use,
      relationship characteristics, perceived risk for HIV, and HIV-related
      communication with the primary male partner. Level of HIV-related communication
      with the primary male partner was associated with the woman's perceived risk for
      HIV and her rating of the openness with which she could communicate with her
      primary partner. Mexican women were less likely than Puerto Rican or Dominican
      women and women with multiple partners were less likely than those with one
      partner to communicate about HIV-related issues with their primary partner. Women
      reporting more condom use with their primary partner were younger, had discussed
      HIV-related issues more with the primary partner, and were less likely to expect
      negative reactions to requests for condom use than those reporting less condom
      use. These results suggest that prevention programmes that increase both general
      and HIV-specific communication between members of a couple may facilitate safer
      sex practices by the couple. Prevention programmes that encourage women to insist
      on condom use should consider the woman's expectations about her partner's
      reaction as a potential barrier to the initiation of safer sex practices.

PMID- 8547358
TI  - Intimacy and sexual risk behaviour in serodiscordant male couples.
AB  - Several studies have demonstrated individual-level determinants of HIV sexual
      risk behaviour. Very little research has been conducted to identify couple-level
      factors associated with unsafe sexual behaviour. As part of a three-year study of
      more than 100 serodiscordant male couples, we conducted an in-depth qualitative
      study of 15 Latino and non-Latino male couples via focus groups and a follow-up
      telephone survey. We identified the sexual risk behaviour that occurs in these
      male couples, their perceptions of susceptibility for HIV transmission, and
      numerous couple-level and intrapsychic factors associated with their risk
      behaviour. We also describe the challenges confronted by these couples and
      barriers to emotional intimacy and couple satisfaction. Finally, we provide
      suggestions for ways of intervening to facilitate improved couple functioning,
      pleasure, satisfaction, and communication, and ways of reducing sexual risk
      behaviour without loss of emotional intimacy.

PMID- 8547359
TI  - Zidovudine adherence among individuals with HIV infection.
AB  - The objective was to investigate the relationships among health beliefs,
      attitudes, and zidovudine compliance in individuals with HIV infection. A survey
      was administered to 52 individuals with HIV infection. The survey items, which
      reflected concerns expressed about zidovudine, were generated based on barriers
      to and benefits of zidovudine and the perceived susceptibility to and perceived
      severity of HIV as described by the health belief model (HBM). These items were
      expressed as attitudes and beliefs. Items were subjected to factor analysis, and
      survey results were correlated with laboratory data to predict adherence to their
      prescribed medication-taking regimen. Data indicated that 42.3% of the subjects
      were compliant with zidovudine. Factor analysis identified four dimensions:
      problems taking and scepticism about zidovudine; degree of concern about HIV;
      perceived severity of HIV; and physical barriers to taking zidovudine. Logistic
      regression analysis (forward conditional entry) identified those who were having
      problems taking zidovudine and who were sceptical about its effectiveness, and
      ethnicity as significant independent predictors of compliance, correctly
      classifying 75% of cases (p < 0.01). The fact that subjects who have problems
      taking zidovudine or are sceptical about the value of zidovudine are less
      compliant, and that this dimension is a significant predictor of compliance,
      suggests that non-compliance is related to attitudes and beliefs about
      zidovudine. This is consistent with the HBM, which holds that the balance between
      barriers and benefits of a health-related behaviour are significant determinants
      of outcome.

PMID- 8547360
TI  - Cross-cultural comparison of US and Nigerian adolescents' HIV-related knowledge,
      attitudes, and risk behaviour: implications for risk reduction interventions.
AB  - Attitudes towards AIDS prevention, AIDS-related knowledge, and sexual behaviour
      of Nigerian adolescents and their African-American counterparts in two geographic
      regions of the United States were compared to assess cross-cultural similarities
      and differences between the adolescents. This study was conducted as the first in
      a programmatic sequence of activities leading toward the adaptation of a risk
      reduction intervention that was developed in the US for implementation with
      Nigerian youths. Subjects (n = 511) completed self-report measures of AIDS
      related knowledge, attitudes towards condoms, attitudes towards AIDS prevention,
      sexual behaviour over the past two months, self- and response efficacy, and
      perceived vulnerability. Between-group comparisons revealed that US adolescents
      were more knowledgeable, held more favourable attitudes towards prevention and
      toward condoms, reported more sex partners, engaged in higher frequencies of
      unprotected vaginal intercourse, and became sexually active at later age than
      Nigerian adolescents. The findings are discussed with respect to their
      implications for translating risk reduction interventions developed in the US for
      African-American adolescents for later cross-cultural implementation with
      adolescents in developing countries where such risk reduction efforts are
      urgently needed.

PMID- 8547362
TI  - HIV/AIDS prevention among female sexual partners of injection drug users in
      Ciudad Juarez, Mexico.
AB  - A participatory community project in the US-Mexico border town of Ciudad Juarez,
      aimed at helping women who are sex partners of male injection drug users to
      reduce behaviours which increase their risk for HIV infection, is described and
      evaluated. The design and implementation of the project were influenced by Paulo
      Freire's pedagogy in the Latin American tradition of 'popular' education, by
      Bandura's self-efficacy concepts, and by David Warner's 'barefoot doctor'
      community health care methodology. Using these approaches the participants were
      directly involved in the development of teaching materials, and curriculum
      content and implementation of the project. The programme was evaluated
      quantitatively using NIDA's AIDS Intake and Follow-up Assessment (AIA/AFA)
      questionnaires, and qualitatively using open ended interviews. While the AIA/AFA
      questionnaires detected small changes in the frequency of condom use among the
      participants, ethnographic interviews detected significant changes in the nature
      of the behaviours which were placing the women at risk. The changes seem to stem
      from an increase in the degree of self-esteem, self-efficacy and awareness of the
      social, economic, and political constraints of their lives. These results
      demonstrate the need for qualitative measures to be incorporated in the
      evaluation of community based health education programmes. A series of
      recommendations is presented to facilitate further development and replication of
      the programme in similar populations.

PMID- 8547361
TI  - Group intervention to improve coping with AIDS-related bereavement: model
      development and an illustrative clinical example.
AB  - Despite the widespread losses from AIDS, there have been no published evaluations
      of mental health interventions for people experiencing AIDS-related bereavement.
      We describe a cognitive behavioural coping model for support group interventions
      with people who experience an AIDS-related loss. The support group model consists
      of six primary components to address grief-related responses and the unique
      features of AIDS bereavement: social support and group cohesion; identification
      and expression of emotion; identification of AIDS loss specific coping
      challenges; recognition of current coping; goal setting; and, implementation of
      adaptive coping to reduce psychological distress. The model integrates theories
      of cognitive behavioural coping within a social support group context. Results of
      a pilot study with four men and four women showed that the intervention model
      cast into eight group sessions significantly reduced depression, intrusive
      experiences, grief reactions, demoralization, and overall psychological distress
      immediately following the intervention and at a 3-month follow-up assessment. The
      intervention appeared to facilitate the adjustment of these bereaved persons and
      warrants further study.

PMID- 8547363
TI  - Operating needle exchange programmes in the hills of Thailand.
AB  - Injecting drug use is increasingly markedly amongst the ethnically distinct
      Hilltribe peoples of northern Thailand in the notorious 'Golden Triangle'. This
      paper reports on the establishing of needle exchanges in three remote Hilltribe
      villages, examining the success and the failure. Up to 60% of adult males and a
      smaller percentage of adult females in these villages are habitual users of opium
      and/or heroin. Overcoming initial concern that needle distribution would
      encourage increased use, the villagers themselves have assumed responsibility for
      much of the needle exchange operation. Prior to the introduction of the needle
      exchanges all the injecting drug users were sharing needles. This behaviour
      changed significantly with the introduction of the exchanges. Reluctance on the
      part of locally-based government officials to participate fully in the programme
      created difficulties in maintaining needle supplies which saw some resumption in
      needle sharing. HIV seroprevalence rates amongst the tested injecting drug users
      remained fairly stable at 33% in February 1993 and 32% in February 1994. The
      conclusion can be drawn that needle exchange programmes are operable in the
      Hilltribe context and that they are the best means of limiting HIV/AIDS
      transmission amongst injecting drug users and the wider community. The success of
      needle exchange programmes, however, is dependent upon co-operation from various
      government agencies and non-government agencies, in addition to the local
      communities. To this end mechanisms ensuring co-operation, training, monitoring
      and evaluation need to be developed alongside the introduction of needle
      exchanges.

PMID- 8547365
TI  - Support service use by persons with AIDS and their caregivers.
AB  - The purpose of this study was to identify factors related to the use and non-use
      of emotional and practical support services by persons with AIDS (PWAs) and their
      informal caregivers. Unmet need for PWA support services and perceived barriers
      to the use of these types of services were also identified. Structured interviews
      were conducted with 472 self-selected informal AIDS caregivers in greater Los
      Angeles and the San Francisco Bay area. Data from a cross-sectional survey
      interview were analysed using logistic regression models fit for three categories
      of service use. Use of support services was substantial in this sample. Case
      management, caregiver HIV status, education, co-residence, and type of
      interpersonal relationship were important predictors of service use. Unmet need
      for PWA services was also substantial. The PWA's unwillingness to use services
      and lack of access were identified as key barriers to service use. Even in the
      presence of an informal caregiver, PWAs require considerable supplemental
      assistance from institutional sources. The presence of informal assistance to
      PWAs does not eliminate the need for institutional support. Moreover, caregivers
      themselves demonstrate considerable need for support.

PMID- 8547364
TI  - Promoting safer sexual practices among young adults: a survey of health workers
      in Moshi Rural District, Tanzania.
AB  - As part of the national effort to prevent further spread of HIV/AIDS, rural
      health workers in Tanzania are asked to promote safer sex practices among the
      sexually active population. We conducted a survey among health workers in Moshi
      Rural District, Kilimanjaro, designed to assess their attitudes, perceived norms
      and self-efficacy with respect to the promotion of safer sexual practices among
      young adults 15-35 years old. Health workers at all private and governmental
      health facilities were included (n = 342; participation rate of 68.4%). We
      observed relatively strong associations between the frequency and quality of
      reported counselling behaviour and perceived norms, attitudes and self-efficacy
      (standardized regression coefficients (beta) of 0.329, 0.252 and 0.159
      respectively). In addition, exposure to behaviour change strategies during formal
      training and marital status of the health workers were associated with
      counselling behaviour (beta of 0.133 and 0.118 respectively). Overall, these
      factors accounted for 40.8% of the observed variance in reported counselling
      behaviour. It is recommended that continued education for health workers focus on
      providing normative support for promoting safer sex, provide information which
      may help foster positive attitudes and teach practical counselling skills to
      further increase the self-efficacy regarding counselling young people.

PMID- 8547367
TI  - World Health Organization Global AIDS Statistics.

PMID- 8547366
TI  - The implications of HIV/AIDS for a range of workers in the Scottish context.
AB  - Although there have been a great many surveys of staff members' attitudes to
      HIV/AIDS, there has been relatively little research which has focused on their
      actual responses to and experiences of AIDS-related work (Barbour, 1994a). In
      addition, much of the published work on AIDS workers assumes that the demands of
      this work are self-evident, contingent upon client contact, and unique to this
      area of work. The research findings presented here suggest that these assumptions
      may be unfounded and certainly do not provide a complete picture of what AIDS
      work involves for staff members. Although some of the stressors reported by
      workers related to concerns explored in existing literature they did not always
      experience these anticipated demands as being especially problematic. Workers
      also reported experiencing problems in responding to demands from more unexpected
      quarters, such as organizational aspects of the work, rather than those stemming
      from the nature of contact with clients. Moreover, many of the demands were not
      unique to HIV/AIDS, but are features of other types of work. In devising training
      programmes for AIDS workers educators need to be alert to the often overlooked
      potential of pre-existing training programmes in operation in other specialties.
      Many of the demands cited by workers as problematic related to the newness of
      such demands in the light of their own employment histories rather than to
      HIV/AIDS work itself, suggesting that individualized training packages might be
      more appropriate. In relation to the retention of staff, it is crucial that the
      many rewards which pertain to this area of work are acknowledged and capitalized
      upon.

PMID- 8547368
TI  - Geriatric assessment technology: international research perspectives.

PMID- 8547369
TI  - Targeting elders for geriatric evaluation and management: reliability, validity,
      and practicality of a questionnaire.
AB  - Geriatric evaluation and management (GEM) is most cost-effective when provided to
      persons at high risk for functional decline or heavy use of health services.
      Identifying high risk members of elderly populations is, therefore, the first
      step in conducting successful GEM programs. We have developed and tested a
      mailed, self-administered, eight-item questionnaire to identify home-dwelling
      elders at risk for heavy use of hospitals. Scored by a logistic formula, this
      questionnaire estimates each respondent's probability of repeated admission (Pra)
      to a hospital within four years. Its primary purpose is to help select elders who
      are likely to benefit from outpatient GEM. We created this instrument by
      analyzing data from half the subjects in the Longitudinal Study of Aging (LSOA);
      its test-retest reliability is high (r = 0.78). In a preliminary test of its
      predictive validity among the other half of the LSOA subjects, the instrument
      prospectively identified high-risk elders who went on to use hospitals at twice
      the rate of their lower-risk peers. In a separate study of its predictive
      validity among low-income urban elders, the instrument again identified a high
      risk group that went on to use hospital days at twice the rate of its lower-risk
      counterpart. In a pilot study, we used the questionnaire to identify potential
      recipients of outpatient GEM. The identified elders appeared to be appropriate
      candidates for GEM. They averaged 9.6 significant medical problems, 6.7
      significant prescription medications, and two IADL limitations. We are now using
      this instrument to identify subjects for a randomized clinical trial of
      outpatient GEM

PMID- 8547370
TI  - A flexible system of detection for Alzheimer's disease and related dementias.
AB  - Brief methods for detecting Alzheimer's disease and related dementias (ADRD) are
      widely used in epidemiological and clinical research, and, increasingly, for
      clinical purposes in health care settings, such as primary medical care and
      geriatric evaluation and management (GEM) units. There are many instruments from
      which to choose for these purposes, but they have generally been developed in
      isolation. Little is known about the gains in precision (incremental validity)
      from using more than one instrument in an integrated manner in the process of
      detection, nor has there been a systematic evaluation of the usefulness of being
      able to choose from a repertoire of instruments to suit specific screening
      contexts. The key characteristics of the techniques featured here, namely,
      brevity and ease of administration, allow such assessments to find a place in
      many different contexts. This paper presents findings supporting specific
      recommendations for a limited battery of brief screening techniques for detection
      of dementia, that can be tailored, standing alone or in combinations, to
      optimally suit particular requirements of (i) precision, or (ii) style of
      administration.

PMID- 8547371
TI  - Development of a hierarchical activities of daily living scale for Chinese stroke
      patients in geriatric day hospitals.
AB  - A culture-specific 4-point hierarchical scale covering self-care, household
      activity and mobility was developed by modifying the Rivermead ADL scale to
      assess the physical function of Chinese stroke patients. Self-care ability (13
      items scored 0/1/2/3 with a maximum of 39) and mobility (8 items scored 0/1/2/3
      with a maximum of 24) were routinely assessed by occupational therapists and
      physiotherapists in stroke patients on admission to and at discharge from two
      geriatric day hospitals (GDHs). Household activity (6 items scored 0/1/2/3 with a
      maximum of 18) was assessed by occupational therapists in non-institutionalized
      patients with self-care scores within 15% of the maximum. The scale was
      acceptable to patients and staff. Graphical representation in profile format
      facilitates the identification of items requiring special attention. Internal
      reliability was high; the Cronbach's alpha for the self-care, household and
      mobility domains was 0.9732, 0.9530, and 0.9787, respectively. The scale was used
      to assess the change in physical function of 436 stroke patients discharged from
      two GDHs in Hong Kong over 18 months. Patients' mean age was 73 years (SD +/-
      8.4), and the female/male ratio 1:3. On average, 38 visits (+/- 32) were made
      over a mean enrollment period of 220 days (+/- 289). Both the self-care and
      mobility scores showed statistically significant improvements at discharge, and
      changes in function exceeded 1/4 of the standard deviation of the initial scores.
      A substudy of 28 stroke patients, in whom household scores were assessed,
      revealed that for those with better initial physical function, a ceiling effect
      was apparent with the self-care score but not with the household or mobility
      scores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547372
TI  - The Timed Test of Money Counting: a simple method of recognizing geriatric
      patients at risk for increased health care.
AB  - The purpose of this prospective study was to measure patients' ability to open a
      purse, take out money, and count it, in order to identify persons in need of
      increased health care. The study population consisted of 183 patients (mean age
      78.9; range: 66-95) in two settings: 78 consecutively admitted geriatric hospital
      patients who could return home, and 105 community-dwelling patients aged 70 years
      or older. None was completely dependent on others, nor severely demented. Time
      for task performance was measured. Further assessment included the Mini-mental
      State Examination (MMSE), Barthel index of ADL, instrumental activities of daily
      living (IADL), socioeconomic status, grip strength, Williams board test, and
      medication profile. The Timed Test of Money Counting (TTMC) was reliable
      (interrater and intrarater), and showed construct and concurrent validity with
      other measures of physical function. There was a strong correlation (p < 0.001)
      between the time required to count money, and to open and close the panel doors
      of the Williams board. The other functional measures were also significantly
      correlated with the TTMC. After 18 months, 26 of the patients had died, and 5
      were lost to follow-up. The remainder were divided into those who had stable
      needs (group I), and those with increasing care needs or nursing home placement
      (group II). Time required for money counting was significantly different (p <
      0.001) between groups (30.9 +/- 17.5 seconds for group I, and 122.6 +/- 94.4
      seconds for group II).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547373
TI  - A simple geriatric assessment measure to assist a consultative team decision for
      nursing home placement.
AB  - In this study, Barthel and Mini-mental State Examination scores were combined and
      examined for their ability to predict a geriatric assessment team's decisions for
      nursing home care. We examined cross-sectional data from a project of
      consultative geriatric assessment for nursing home applicants in a high
      socioeconomic status area of Sydney, Australia. The maximum combined score was
      160, and a "grey zone" between 100 and 140 was identified where classification
      errors were greater than 30%. Above 140, most patients were assigned by the team
      to other care, and below 100, nursing home care was recommended for most. The
      effectiveness of a classification test will be increased by identification of a
      grey zone so that if patients fall within this zone, greater care can be taken in
      the decision-making process. Given the select nature of subjects in this
      analysis, the generalizability of the derived combined score will be limited.
      However, the study illustrates one approach that may be taken in the development
      of classification methods to aid decision-making in the clinical or screening
      settings.

PMID- 8547374
TI  - The clock drawing test as a cognitive screening tool for elderly patients in an
      acute-care hospital.

PMID- 8547375
TI  - Epidemiology of adverse clinical events (ACEs) as a dynamic measure of geriatric
      care management.

PMID- 8547376
TI  - Computerized geriatric assessment for geriatric care management.

PMID- 8547377
TI  - A proposal for an integrated multidisciplinary assessment battery in elderly
      stroke patients.

PMID- 8547378
TI  - A model of regular geriatric follow-up by home visits to selected patients
      discharged from a geriatric ward: a randomized controlled trial.
AB  - The aim of this randomized controlled trial was to describe and evaluate a model
      of regular follow-up by home visits to selected elderly patients discharged from
      a geriatric ward. Ninety-seven patients were randomized to receive regular follow
      up visits by a geriatric team at 1, 3, 8 and 16 weeks after discharge, and 96
      patients to receive standard care. Based on the geriatric evaluation, medical and
      social adjustment was carried out, if indicated. Six months after discharge,
      significantly more patients in the intervention group were allocated to home help
      (p < 0.05), but only 42 (44%) were readmitted to a hospital, vs 62 (64%) in the
      control group (p < 0.005). Differences between the groups in mortality and
      nursing-home placement were not statistically significant. Regular follow-up home
      visits by a geriatric team after in-patient geriatric evaluation and management
      reduce the risk of hospital readmissions among highly selected frail geriatric
      patients.

PMID- 8547379
TI  - Effects of a geriatric inpatient unit on elderly home care patients: a controlled
      trial.
AB  - This was the first controlled trial to test the value of bringing elderly
      community-dwelling home care program patients into a hospital geriatric
      assessment unit. Elderly community-dwelling patients (N = 312; mean age = 78
      years) who belonged to a supervised home-care population were randomized into
      intervention (N = 104) and control groups (N = 208). Patients in the intervention
      group underwent a comprehensive multidisciplinary geriatric assessment in an
      inpatient geriatric assessment unit (mean length of stay, 16.5 days). Controls
      continued with usual home care. At baseline, the two groups were comparable. By
      three months, the intervention group had more positive changes in general health,
      continence, housekeeping and satisfaction with care. However, by 12 months, these
      differences were no longer statistically significant. During the follow-up year,
      the intervention group had fewer days in health center hospitals. However, since
      controls had no initial days in the geriatric unit, there was no net difference
      in cumulative institutional days. We conclude that the benefits of this
      assessment approach were relatively mild and apparently temporary. More studies
      of alternative assessment schemes are needed, and different targeting models
      should be studied.

PMID- 8547380
TI  - The Sepulveda GEU Study revisited: long-term outcomes, use of services, and
      costs.
AB  - The randomized controlled trial of the Geriatric Evaluation Unit (GEU) at the
      Sepulveda Veterans Hospital was the first to document the clinical and cost
      effectiveness of hospital-based comprehensive geriatric assessment (CGA). Frail
      elderly inpatients were assigned randomly to the GEU for CGA, therapy,
      rehabilitation, and placement (N = 63), or to standard hospital care (N = 60). At
      one year, GEU patients had much lower mortality (24% vs 48%) and were less likely
      to have been discharged to a nursing home (NH) (13% vs 30%), or to have spent any
      time in NHs (27% vs 47%). GEU patients were more likely to improve in personal
      self-maintenance and morale. Further, controls had substantially more acute-care
      hospital days, NH days, and hospital readmissions, resulting in higher direct
      institutional care costs, especially after survival adjustment. Here, we report
      the results of long-term follow-up. There was a significant survival effect
      through two years. Despite prolongation of life, there was no indication that
      quality of life was worse for survivors in the GEU group. In fact, the proportion
      of persons independent in > or = 2 ADLs at two years was somewhat higher for GEU
      patients (0.44) than controls (0.33) (z = 1.27; p = 0.056). By three years, 43%
      of GEU subjects and 38% of controls were still alive. Over the entire 3-year
      period, the per capita direct cost difference was not significant, either before
      or after survival adjustment (unadjusted: $37,091 GEU vs $34,205 control;
      survival-adjusted: $54,315 GEU vs $63,362 control; p = 0.17).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8547381
TI  - Methodologic challenges of randomized controlled studies on in-home comprehensive
      geriatric assessment: the EIGER project. Evaluation of In-Home Geriatric Health
      Visits in Elderly Residents.
AB  - Previous controlled studies have shown that preventive home visits are a
      promising method for disability prevention in elderly persons; however, due to
      the lack of data on cost effectiveness and optimal intervention methods, there is
      still debate on their usefulness. Therefore, additional controlled studies must
      use new methods to resolve these unanswered issues. We present a novel approach
      used in the project EIGER (Evaluation of In-Home Geriatric Health Visits in
      Elderly Residents), an ongoing randomized controlled trial of preventive home
      visits in community-residing persons aged 75 years and older in Bern,
      Switzerland. The intervention consists of in-home visits with structured
      comprehensive geriatric assessment and follow-up by specially trained nurses who
      collaborate with geriatricians and an interdisciplinary team. Special methods
      were used to optimize the sample size, to improve the health care cost analysis,
      to minimize and explore refusal to participate, to apply stratified randomization
      for subgroup analysis, and to evaluate the intervention process with a tracer
      method. Selected baseline findings (N = 791, mean age 82 years, 73% female)
      include uncontrolled systolic hypertension (54%), balance/gait disorder (9%),
      cognitive impairment (7%), 6 or more medications (21%), depressive symptoms
      (10%), and impaired basic ADL (15%). Baseline findings demonstrate that this
      study is likely to contribute to some of the unresolved issues of in-home
      prevention for older persons.

PMID- 8547382
TI  - A multicenter randomized trial of comprehensive geriatric assessment and
      management: experimental design, baseline data, and six-month preliminary
      results.
AB  - Between October 1992 and July 1993, 11 Northern Italian geriatric departments
      systematically screened 1386 inpatients hospitalized for at least 10 days. Of
      those screened, 74% (N = 1019) were excluded by one or more of 7 exclusion
      criteria; 32% (N = 118) of the 367 remaining subjects failed to meet more than 1
      of 8 inclusion criteria. The 11 Geriatric Evaluation Units (GEUs) examined the
      remaining eligible 249 inpatients with a uniform comprehensive geriatric
      assessment (CGA) plan, which included a number of validated assessment scales. Of
      those evaluated, 39% (N = 97) were ineligible for the study because of being
      unwilling, noncompliant, too sick or "not truly frail", and the remaining 152
      (11% of all patients screened) were randomly enrolled in two groups; 79 were
      assigned to the GEU (experimental group), and 73 to standard care in the National
      Health Care System (control group). At entry there was no statistically
      significant difference between the two groups. At 6 months, preliminary results
      are encouraging; GEU patients had a lower mortality than controls (2 vs 8, 2.5%
      vs 10.9%; p < 0.05). Slight differences were seen in both clinical-cognitive
      affective-functional status and the use of health and social care resources. Only
      3 subjects dropped out, 8 refused further follow-up, and 3 went to a nursing
      home. We conclude that a standardized selection plan can recognize frail elderly
      inpatients and that GEU care seems to achieve good results.

PMID- 8547383
TI  - Evaluation of a geriatric consultation unit in an acute university hospital.

PMID- 8547384
TI  - Effectiveness of geriatric evaluation and management: design of a study.

PMID- 8547385
TI  - The role of geriatric consultation in elderly urologic patients.

PMID- 8547386
TI  - The use of urinary catheters among elderly patients admitted to an acute medical
      ward.

PMID- 8547387
TI  - Assessment of quality of care in a geriatric acute care unit: a preliminary
      report.

PMID- 8547388
TI  - A randomized trial of multidisciplinary in-home care for frail elderly patients
      awaiting hospital discharge.

PMID- 8547389
TI  - A geriatric evaluation and management (GEM) program: evaluation of patient
      outcomes.

PMID- 8547390
TI  - The complementarity of qualitative and quantitative methods in the evaluation of
      institutional environments.

PMID- 8547392
TI  - Bibliography of the current world literature. Therapeutic modalities.

PMID- 8547391
TI  - Quantifying functional ability to predict health-care use of elderly persons.

PMID- 8547393
TI  - Bibliography of the current world literature. Breast.

PMID- 8547394
TI  - Epidemiology, prevention, and early detection of breast cancer.
AB  - Studies of the etiology, early detection, and prevention of breast cancer
      reported in the past year are reviewed in this paper. Studies of the etiology of
      breast cancer include reports on genetic and environmental factors. A major
      advance in the study of inherited forms of breast and ovarian cancer occurred
      with the identification of the BRCA1 gene. A second breast cancer susceptibility
      gene, the BRCA2 gene, was localized to chromosome 13q12-13. Multiple mutations in
      the BRCA1 gene have been identified, presenting a challenge for the development
      of predictive testing. Controversy continues over the association between hormone
      replacement therapy and the development of breast cancer. A study of exercise
      suggests a strong protective effect against the development of early onset breast
      cancer. Recent studies have failed to find a strong link between dietary fat
      intake and the development of breast cancer. A meta-analysis of studies of the
      efficacy of screening for the prevention of breast cancer mortality demonstrates
      a significant reduction in mortality among women 50 years of age and older. A
      lowering of breast cancer mortality for women aged 40 to 49 was only demonstrated
      after 10 to 12 years of follow-up. The risks and benefits of tamoxifen therapy, a
      potential breast cancer chemoprevention agent, continue to be clarified. Adverse
      effects on the endometrium, including an increased risk of endometrial cancer,
      have been reported. Beneficial effects include an improved cardiovascular risk
      profile and preservation of bone mineral density among postmenopausal women.

PMID- 8547395
TI  - Recent advances in breast cancer biology.
AB  - Breast cancer represents a significant worldwide public health problem as well as
      an excellent model system for examining many aspects of tumor biology and
      genetics. As the understanding of the biology of breast cancer expands, this new
      knowledge can be put to use in efforts to diagnose, treat, and prevent breast
      cancer. In this review we highlight recent advances in breast cancer biology in
      the areas of genetics, immunobiology, and molecular biology, with particular
      emphasis on tumor-suppressor genes, minimal disease detection, growth factor
      receptors, cell cycle regulators, and mediators of apoptosis.

PMID- 8547396
TI  - Pathology of preinvasive and excellent-prognosis breast cancer.
AB  - Little has been added in the past year to our knowledge of the premalignant
      lesions that have implications of increased subsequent cancer risk. However,
      studies of molecular biologic associations of these lesions are proceeding. The
      heterogeneous nature of ductal carcinoma in situ and its clinical implications
      continues to evolve. Several studies of ductal carcinoma in situ have confirmed
      that this entity extends in continuity within the breast whether associated with
      invasive carcinoma or not. Therapeutic stratification of ductal carcinoma in situ
      lesions depending on their grade and size is widely accepted, however, formal
      larger cooperative studies are necessary. Therapeutic use of histologic grading
      and recognizing special histologic subtypes continues to gain importance. Studies
      detailing the the use of grading as an additive measure of the predictiveness of
      staging, as well as documentation of interobserver agreement when fostered by
      rule-structured agreement, dominate the current literature on this subject. The
      use of stereotactically guided needle biopsy is rapidly gaining a broad
      consensus. Precise guidelines for management of borderline diagnoses are under
      development.

PMID- 8547397
TI  - Surgery for early and minimally invasive breast cancer.
AB  - Limiting morbidity without sacrificing outcome remains paramount for patients
      with minimally invasive breast cancer, particularly regarding diagnosis, local
      disease control, limiting axillary dissection, and identifying the optimal timing
      for surgery. Stereotactic biopsy is evolving as a viable alternative to surgical
      biopsy, but it awaits confirmation in a randomized prospective study before its
      adoption on a routine basis. Breast-conserving therapy continues to offer local
      control rates similar to mastectomy, except for lesions with positive-excision
      margins, an extensive intraductal component, and perhaps in young patients and
      those with either lobular carcinoma or multifocal disease. Factors that provide
      prognostic information currently obtained by axillary dissection have not been
      identified, and hence axillary dissection remains a mainstay of treatment.
      Sentinel node biopsy requires further refinements and confirmation before its
      universal acceptance. Premenopausal patients undergoing surgery during the
      follicular phase of the menstrual cycle appear to fare poorly, thereby requiring
      further investigation.

PMID- 8547398
TI  - Radiation therapy for breast cancer.
AB  - As data bases mature, more in-depth analyses of results, with special attention
      to late dose and volume effects and second cancers, are appearing in the
      literature. In the continuing effort to minimize late effects, the importance of
      the boost dose is being reexamined, in relationship to the increasingly
      sophisticated margin information now available from most pathology laboratories.
      As well, patients are increasingly being grouped by various risk factors into
      subsets rather than receiving standard management as dictated by their stage of
      disease. This year the special needs of the elderly patient is being focused on,
      with regard to the need for dissecting the axilla and observations regarding the
      role of tamoxifen in both distant and local control.

PMID- 8547399
TI  - Adjuvant systemic therapy for breast cancer.
AB  - The continued research efforts in the field of breast cancer adjuvant therapy are
      translating into a better understanding of the real, but still modest, impact on
      patient outcome. Recent publications are focusing either on secondary leukemias
      or on secondary solid tumors, which are associated with the use of adjuvant
      chemotherapy or adjuvant tamoxifen, respectively. These attempts at an improved
      risk-benefit assessment of classic adjuvant treatment for breast cancer are to be
      encourage. In parallel, there is an urgent need for innovative treatment
      approaches that have to be carefully evaluated through prospective randomized
      clinical trials. These include increasing chemotherapy dose intensity, changing
      timing or scheduling of drug administration, or moving new active agents, such as
      the taxoid compounds, to the adjuvant setting. Major efforts still need to be
      done in using new molecular markers of tumor aggressiveness for an improved
      assessment of a patient's individual risk of relapse. Finally, increasing
      attention is being paid to optimal therapy for elderly patients.

PMID- 8547400
TI  - Metastatic breast cancer.
AB  - Tamoxifen as adjuvant systemic treatment after first isolated locoregional
      recurrence of breast cancer has been shown to decrease the subsequent
      locoregional relapse rate, but it affects neither distant metastases nor
      survival. In metastatic disease, tamoxifen has not improved response when added
      to ablation of ovarian function. The cyclical sequential use of tamoxifen with
      megestrol acetate has not increased the response over tamoxifen alone. Aromatase
      inhibitors are an expanding field; formestane and vorozole are effective agents,
      and letrozole shows promise. In chemotherapy, major interest has focused on the
      use of taxoids, with high activity being reported for both paclitaxel and
      docetaxel, the latter being particularly effective as a second-line treatment.
      Reports continue to reaffirm the effectiveness of vinorelbine. The in vitro
      ability of quinidine to reverse resistance to anthracyclines has not been
      repeatable in a clinical setting. The evaluation of high-dose chemotherapy with
      bone marrow support continues to be explored, but this approach has thus far not
      been demonstrated to improve clinical outcome in advanced disease. The intra
      arterial administration of chemotherapy appears to have a useful palliative role
      in selected patients with locoregional disease.

PMID- 8547401
TI  - Psychosocial issues in breast cancer.
AB  - Over the past year, increasing research attention has been devoted to the issue
      of women at increased risk of developing breast cancer. These articles focus on a
      range of issues from recruiting high-risk women into breast cancer trials to
      recommendations for assessment and counseling women with a family history of
      breast cancer. In addition, continuing research attention has focused on quality
      of life, symptom management, and articles related to physician-patient
      communication. This review summarizes and critiques publications in these areas,
      and it includes articles reviewing the status of research in psychosocial
      oncology.

PMID- 8547402
TI  - Multidrug resistance proteins and other drug transport-related resistance to
      natural product agents.
AB  - The term multidrug resistance is defined in this article as cellular resistance
      to anticancer agents due to a decreased concentration of active drug at the
      target sites that is caused by increased metabolism or altered transport or
      routing of the active drug species. Resistance related to alterations in the drug
      targets or apoptotic pathways is not discussed. Until recently multidrug
      resistance was associated almost exclusively with p-glycoprotein (Pgp)
      overexpression. However, other non-Pgp-related mechanisms have been tracked down.
      It has been shown that transfection of the gene that encodes a novel drug
      transport protein, the multidrug resistance protein, induces cross-resistance for
      many multidrug resistance drugs as well as active transport of daunorubicin from
      tumor cells. Surprisingly, it has also been found that multidrug resistance
      protein mediates transport of negatively charged species that are not classic
      multidrug resistance drugs, such as leukotriene C4 and other glutathione
      conjugates as well as negatively charged dyes. It was therefore suggested that
      multidrug resistance protein is identical with the multispecific organic anion
      transporter. The transport rate of several positively charged drugs (vincristine,
      rhodamine-123, daunorubicin) by multidrug resistance protein appeared to be
      dependent on the cellular glutathione levels. Multidrug resistance protein seems
      to be constitutively expressed in normal tissues at a low level with few tissues
      having higher expression. Multidrug resistance protein overexpression in in vitro
      selected MDR cell lines occurs relatively frequently in lung cancer and leukemia
      cell lines and often precedes Pgp overexpression. Differential expression has
      been demonstrated in tumor samples, which suggests a role in resistance to
      chemotherapy in at least certain tumor types. Modulation studies of multidrug
      resistance protein activity are still scarce. Other non-Pgp, non-multidrug
      resistance protein multidrug resistance mechanisms probably exist but have not
      been identified at the molecular level as yet.

PMID- 8547403
TI  - Regulation of apoptosis by bcl-2 family proteins and its role in cancer and
      chemoresistance.
AB  - In essentially all tissues that have self-renewal capacity, there exists a
      delicate balance between cell production by mitogenesis and cell loss due to
      programmed cell death (PCD), which maintains total cell numbers within
      physiologically appropriate ranges. Genetic alterations that either dysregulate
      the cell division process, resulting in faster cell proliferation, or that affect
      physiological cell death mechanisms that cause slower rates of cell loss, occur
      frequently in human tumor cells and contribute to the clonal expansion of cancer
      cells in vivo. PCD is an active form of cell suicide that sometimes requires new
      gene expression for its initiation and that in many, but not all, cases
      culminates in a characteristic set of biochemical and morphological events. These
      include genomic DNA cleavage by endonucleases, chromatin condensation (pyknosis),
      nuclear fragmentation, proteolysis of cytoskeletal and other proteins, plasma
      membrane blebbing, and cell shrinkage. In many ways, these biochemical events can
      be viewed as a form of cellular autodigestion in which the macromolecular
      components of cells are degraded so that their constituent subunits can be
      recycled in the body. When present in their classical form, the morphological
      events accompanying this type of cell death are broadly termed apoptosis. Though
      well known for its role in the normal physiological cell death mechanisms that
      maintain tissue homeostasis, a wide variety of pathological conditions and
      external factors can trigger the PCD pathway. Included among these apoptotic
      stimuli are essentially all chemotherapeutic drugs and radiation, a finding of
      considerable relevance to our understanding of how currently available treatments
      of cancer work and for devising strategies for improving them. In this review,
      the regulation of PCD by members of the bcl-2 family of proteins is discussed,
      primarily within the context of human cancers where abnormalities in the
      expression of BCL2 family genes frequently occur and contribute both to the
      origins of cancer and our difficulty in treating it.

PMID- 8547404
TI  - Cancer therapy and p53.
AB  - Apoptosis is now recognized as an important process in tissue homeostasis. In
      malignancy, mutations in apoptotic programs may promote tumor progression as well
      as reduce the efficacy of cancer therapy. Recent studies identify the product of
      the p53 tumor-suppressor gene as an important regulator of apoptosis in tumor
      cells. At the same time, clinical studies implicate p53 mutations in pleiotropic
      resistance to cytotoxic cancer therapy. Together, these observations suggest that
      inactivation of p53 promotes resistance to anticancer agents by attenuating
      apoptosis. This view identifies p53 as a potential drug target and suggests
      several strategies for therapeutic intervention.

PMID- 8547405
TI  - Anticancer drugs acting against signaling pathways.
AB  - This review deals with anticancer drugs with activity against signaling targets
      that have been studied in cancer patients. The major categories of drugs studied
      so far are modulators of the activity of protein kinase C, inhibitors of protein
      kinase A, protein tyrosine kinase, and receptor-operated Ca2+ channels. Drugs
      that may modulate ras function have also been studied. None of the agents have
      yet received extensive clinical trials. Toxicities and anecdotal cases of
      antitumor activity have been reported. There are a number of other anticancer
      drugs with activity against signaling targets awaiting clinical trial.

PMID- 8547406
TI  - Interferons: laboratory to clinic investigations.
AB  - Interferons are pleiotropic cytokines that exhibit multiple biological effects on
      cells and tissues, including antiproliferative, antiviral, and immunomodulatory
      activities. Despite the well-documented activity of interferons in the treatment
      of certain malignancies, the precise mechanisms by which these cytokines inhibit
      malignant cell growth remain unknown. Recently, several laboratory studies have
      provided important clues on the cellular events elicited during the binding of
      interferons to their receptors on malignant cells. The continuation and expansion
      of such studies should help us understand the mechanisms by which interferons
      elicit their antitumor effects and provide a basis for the development of new
      strategies in their clinical use.

PMID- 8547407
TI  - Therapeutic strategies for cytokines.
AB  - Cytokines have now entered the clinical arena as important mediators of the
      immune system and the hematopoietic system. The interleukins (ILs) in clinical
      trials as anticancer agents at this time include IL-1, IL-2, IL-4, IL-6 and IL
      12. Other cytokines with demonstrated anticancer activity include the interferons
      and tumor necrosis factor. The complexity of this system is gradually being
      understood, and the clinical efficacy of these agents is being developed. This
      review is an update of the status of several of these agents in clinical
      investigations.

PMID- 8547408
TI  - Recent advances in hormonal therapy for cancer.
AB  - Hormonal manipulation of cancer is no longer confined to the use of effective
      antiestrogen therapy for breast cancer or surgical or hormonal castration for
      prostate cancer. A broader acknowledgment of the potential of different hormonal
      ligands to evoke cell cycle arrest to prevent the progress of neoplastic
      transformation, and even to elicit active cell death, has expanded the concept of
      hormonal therapy. The use of retinoids and deltanoids in conjunction with
      antiestrogens and antiandrogens is progressing into clinical trials. The use of
      glucocorticoids in conjunction with cyclic AMP may enhance apotosis induction.
      The use of antiandrogens in conjunction with cytotoxic therapy may diminish the
      risk of bcl-2-mediated resistance in prostate cancer. Innovative use of
      sequential and synergistic hormonal manipulations based on an expanding
      understanding of transcriptional regulation promises to advance this science.

PMID- 8547409
TI  - Preventing pelvic infection after abortion.
AB  - Pelvic infection is the commonest complication of legal abortion. The presence of
      lower genital tract infections increases the risk of complications, and women
      requesting abortion are at significant risk of harbouring sexually transmitted
      diseases (STD). Prophylactic antibiotic treatment can decrease the rate of post
      abortal sepsis, but the optimum regime is unclear. In particular, patients with
      Chlamydia trachomatis infection, and bacterial vaginosis would appear to be at
      increased risk, and detection and treatment of these conditions can lower this
      risk. The opportunity to screen and treat for STD presents itself in this
      setting, allowing patients and their sexual contacts to benefit, with a decrease
      in the infected pool in the community.

PMID- 8547410
TI  - Management of cytomegalovirus infection. The Jefferiss Wing Therapeutics and
      Protocols Group.

PMID- 8547411
TI  - Antiviral chemotherapy in genital herpes simplex virus infections.

PMID- 8547412
TI  - HIV neurology grey case.

PMID- 8547413
TI  - When to perform the final HIV antibody test following possible exposure.
AB  - The senior consultant and senior health adviser in all genitourinary medicine
      clinics in the UK were sent a questionnaire on HIV testing practice in seven
      clinical scenarios. For each scenario the recommended time interval between
      possible exposure and final HIV antibody test varied from a minimum of 3 months
      to a maximum of over 5 years. The results show 2 broad patterns: when the contact
      was not someone known to be HIV positive the commonest recommended time interval
      was 3 months; for a known exposure to HIV the commonest recommendation was 6
      months. Only 16 out of the 151 clinics replying had a written policy setting out
      the interval to elapse between possible exposure to HIV and the final test for
      HIV antibodies. Variation of practice within clinics is less where written
      policies exist. Some staff in clinics are recommending inappropriately long
      intervals before the final HIV test.

PMID- 8547414
TI  - Hospital service utilization by HIV/AIDS patients and their management cost in a
      provincial genitourinary medicine department.
AB  - The hospital management of 108 HIV/AIDS patients cared for by the genitourinary
      medicine department, Sheffield, UK between 1984-93 was retrospectively studied to
      quantify the services utilized by these patients and to detail the management
      costs (1993 price) of outpatient (OP) services, inpatient (IP) care,
      investigational services and therapeutic provisions. The services utilized and
      cost are presented separately for the different clinical stages of the infection
      and as per patient year. Of the 108 patients, 95 (88%) were males and 13 (12%)
      females; most males (76.8%) acquired the infection through homosexual exposure,
      while 46% of females acquired it heterosexually. The mean number of OP
      consultation per asymptomatic, symptomatic non-AIDS and AIDS patient years were
      11.6, 16.4 and 32.8 respectively; the mean number of IP episodes for each of
      these clinical groups were 0.15, 0.83 and 3.88 with IP stays 0.7, 3.5 and 40.6
      days per patient year respectively. The annual costs of OP care (45.26 pounds per
      consultation), drugs and investigations were, respectively 525 pounds, 213 pounds
      and 153 pounds per asymptomatic patient year, 742 pounds, 2097 pounds and 224
      pounds per symptomatic non-AIDS patient year and 1485 pounds, 2928 pounds and 382
      pounds per AIDS patient year. The average annual OP drug cost per patient year
      showed little change since 1988. However, in the AIDS group, contributions from
      differing drug classes showed significant changes; while the contribution of
      antiretroviral drugs fell from 80.2% of the drug cost per AIDS patient year in
      1990 to 31.3% in 1993, that from antibiotics rose from 0.3% in 1990 to 26.4% in
      1993 and other antivirals from 9.4% in 1988 to 22.6% in 1993. These changes were
      related to lower recommended daily dosage of zidovudine and to wider prescription
      of antibiotics for atypical mycobacterial infections and domiciliary gancyclovir
      for CMV infection. The costs of annual mean IP care, IP drugs, IP investigations
      and IP procedures per AIDS patient year were 5926 pounds (146 pounds per IP
      stay), 2983 pounds, 282 pounds and 145 pounds respectively. The overall
      management cost of one AIDS patient year was 14,131 pounds and lifetime AIDS
      management cost, based on a mean survival of 17 months, a little more than 20,000
      pounds. The annual management cost of an asymptomatic and symptomatic non-AIDS
      patient year is approximately 1/14th and 1/4th of the cost of an AIDS patient
      year.

PMID- 8547416
TI  - Gonorrhoea as an indicator of altered sexual behaviour and as a surrogate marker
      of HIV concern: a 13-year analysis in Newcastle.
AB  - It has been proposed that changes in sexual behaviour arising out of concerns
      regarding HIV infection can be inferred by changes in the incidence of
      gonorrhoea. We have reviewed data on gonococcal isolates in Newcastle over the
      last 13 years and looked at changes in relation to HIV test requests, new cases
      of HIV infection and media campaigns. HIV testing has been available in the
      clinic since late 1985. There was a steady decline in cases of gonorrhoea from
      1985-1991 and then as in other areas an increase in incidence was seen among
      homosexual and bisexual men. The majority of this recent increase was due to
      pharyngeal infection. Sexual behaviour may have changed but this cannot be purely
      attributed to HIV concerns. HIV testing began after the incidence of gonorrhoea
      in England was already falling and we found no relationship between trends in
      gonorrhoea, HIV test requests and new cases of HIV infection.

PMID- 8547415
TI  - Epidemic spread of plasmid-mediated tetracycline resistant Neisseria gonorrhoeae
      in Zaire.
AB  - A cohort of 650 prostitutes from Kinshasa, Zaire, was followed at monthly
      intervals for sexually transmitted diseases as part of an HIV intervention
      project. Neisseria gonorrhoeae isolates, obtained during a period of 30 months,
      were auxotyped, serotyped and tested for antimicrobial susceptibility. Among 1085
      gonococcal isolates tested, 725 (67%) produced beta-lactamase (PPNG) and 323
      (30%) showed plasmid-mediated resistance to tetracyline (TRNG). Over time, the
      prevalence of PPNG varied between 60 and 73%, while the level of TRNG increased
      from 11 to 45%.

PMID- 8547417
TI  - Intralesional interferon for the treatment of recalcitrant molluscum contagiosum
      in HIV antibody positive individuals--a preliminary report.
AB  - Molluscum contagiosum is common in HIV disease and available therapies have a
      poor success rate and require frequent clinic visits. Interferon alpha has been
      used to treat recalcitrant condylomata acuminata and this study was undertaken to
      assess the use of this treatment in unresponsive molluscum contagiosum. A total
      of 30 molluscum contagiosum were injected with one megaunit of interferon alpha
      weekly for 4 weeks; 11 molluscum contagiosum completely cleared and 18 reduced in
      size by over 50%. Molluscum less than 0.5 cm in diameter, and those in patients
      without AIDS were more likely to respond. No surrounding lesions changed in size.

PMID- 8547418
TI  - Azole drug resistance as a cause of clinical relapse in AIDS patients with
      cryptococcal meningitis.

PMID- 8547419
TI  - Syphilitic aortic aneurysm and squamous cell carcinoma of the penis: a case
      report.

PMID- 8547420
TI  - Haemoglobin SC disease presenting as a case of priapism to a GUM clinic.

PMID- 8547421
TI  - An audit of nurse treatment sessions for female patients with genital warts.

PMID- 8547422
TI  - An audit of hepatitis B vaccination compliance rates in two genitourinary
      medicine clinics.

PMID- 8547423
TI  - National vulvodynia questionnaire.

PMID- 8547424
TI  - Morbidity and disease prevalence in male and female sexual contacts of patients
      with genital chlamydial infection.

PMID- 8547425
TI  - Retinoic acid derivatives and HPV infection.

PMID- 8547426
TI  - Falling prevalence of Chlamydia trachomatis infection--an alternative
      explanation.

PMID- 8547427
TI  - Targeting young people for sexual health counselling.

PMID- 8547428
TI  - Distribution of endothelin receptor subtypes in the rat kidney. Renal and
      haemodynamic effects of the mixed (A/B) endothelin receptor antagonist bosentan.
AB  - The paracrine renal endothelin system has been implicated in acute and chronic
      kidney diseases. However, there are only few data about the expression of
      endothelin receptor subtypes and their impact on renal function in the normal rat
      kidney. Therefore, we analyzed the age-dependent expression of endothelin
      receptors (endothelin receptor A and B) using Scatchard analysis, in vitro and in
      vivo receptor autoradiography. Furthermore, we investigated the effects of the
      mixed (A/B) endothelin receptor antagonist bosentan on haemodynamic and renal
      function in conscious chronically instrumented rats. The renal endothelin
      receptor A and endothelin receptor B expression is age-dependent. The relative
      amount of endothelin receptor A significantly decreased with age, whereas the
      endothelin receptor B significantly increased with age. Compared to the other
      renal structures, a high endothelin receptor density (endothelin receptor B >>
      endothelin receptor A) was seen in the renal tubules and even more in the
      glomeruli. Bosentan blocks both the pressor and depressor response of endothelin.
      Blocking of both endothelin receptor subtypes using bosentan without application
      of endothelin, on the other hand, did not alter blood pressure, heart rate, renal
      blood flow, water excretion or glomerular filtration rate, but significantly
      decreased sodium excretion.

PMID- 8547429
TI  - Plasma Lipoprotein(a) and its relationship with disease activity in patients with
      Behcet's disease.
AB  - Behcet's disease is characterized by orogenital ulcerations and ocular lesions.
      Other features include arthritis, thrombophlebitis, neurological abnormalities
      and skin lesions. The disease is characterized by a relapsing inflammatory
      process of unknown aetiology. Lipoprotein(a) is an LDL-like particle with a large
      glycoprotein called apolipoprotein(a) attached to its apolipoprotein B moiety
      through one or more disulphide bonds. Apolipoprotein(a) is related to plasminogen
      from which the enzyme plasmin, that hydrolyses fibrin blood clots, is released by
      tissue plasminogen activators. The unique structural features of Lp(A) give it
      the potential for atherogenic and thrombogenic activities. In the present study
      35% of patients with Behcet's disease were shown to have higher Lp(a)
      concentrations than the cut-off point (0.30 g/l) for atherosclerosis. Plasma
      Lp(a) concentrations in the remission period were also found to be lower than
      during the active period in the same patients (23% decreased). Lp(a) showed
      significant correlations with acute phase reactants such as erythrocyte
      sedimentation rate, polymorphonuclear leukocytes and polymorphonuclear leukocyte
      elastase activity. Therefore, it was concluded that the fluctuations of plasma
      Lp(a) levels with the activity of disease may be a contributing risk factor in
      the development of thrombogenic complications in patients with Behcet's disease.

PMID- 8547430
TI  - Simultaneous assessment of bone collagen synthesis and degradation in patients
      with different malignant tumours. Comparison with the results of 99mTc-methylene
      bisphosphonate bone scintigraphy.
AB  - We report on the diagnostic validity of the serum concentrations of the C
      terminal propeptide of type I procollagen (a marker of bone formation) and of the
      urinary excretion of deoxypyridinoline (a marker of bone resorption) in a
      consecutive series of 89 tumour patients who were routinely examined by 99mTc
      methylene bisphosphonate bone scintigraphy for detection of bone metastases. Z
      score analysis reveals that the discriminating power of deoxypyridinoline is
      superior to that of calcium excretion whereas the discriminating power of the C
      terminal propeptide concentrations is inferior to that of bone alkaline
      phosphatase values. Accuracy (as assessed by the area under the receiver
      operating characteristic curve) was 0.75 for deoxypyridinoline and 0.82 for the C
      terminal propeptide. Combination of both markers did not yield an increase of
      accuracy (0.82) compared with the determination of the C-terminal propeptide
      concentrations alone. There was a correlation (r = +0.398; p < 0.0001) between C
      terminal propeptide concentrations and deoxypyridinoline excretion values in the
      group of 89 patients examined. Further studies should be done to elucidate
      whether the determination of bone collagen turnover is suitable as a screening
      procedure for detecting bone metastases.

PMID- 8547431
TI  - Lactate dehydrogenase activity of platelets in diabetes mellitus.
AB  - Lactate dehydrogenase (L-lactate : NAD+ oxidoreductase, EC 1.1.1.27) activity has
      been measured on the subpopulations of platelets obtained from blood of diabetic
      patients. Small, but not large platelets show a lactate dehydrogenase activity
      higher than that of controls. Moreover, a positive statistically significant
      correlation was found between the activity of small platelets and the percent of
      glycated haemoglobin, while no correlation was obtained in the case of large
      platelets. Since we previously demonstrated that lactate dehydrogenase activity
      of small platelets is exceedingly high in some clinical and experimental
      conditions, our results not only confirm the involvement of platelets in diabetes
      but provide more evidence in support of our previous hypothesis of a relationship
      between lactate dehydrogenase and in-vivo platelet activation.

PMID- 8547432
TI  - Time changes of creatine kinase and creatine kinase-MB isoenzyme versus
      discrimination values in the diagnosis of acute myocardial infarction: what is
      the optimal method for displaying the data?
AB  - We wanted to determine the optimal method for displaying data for the clinical
      evaluation of patients with possible acute myocardial infarction. Our primary
      question was, are the time changes (slopes) of the enzyme tests better predictors
      of disease than the discrimination values, i.e., the cut-off points? We studied
      152 patients with and 114 without a diagnosis of acute myocardial infarction in
      their medical records. For patients with acute myocardial infarction, we found
      the most discriminating tests, in decreasing order of the area of the ROC curves,
      to be the creatine kinase-MB slope at 0 to 12 hours, the creatine kinase-MB slope
      at 12 to 24 hours, the creatine kinase-MB values between 12 and 24 hours, and the
      creatine kinase-MB values between 0 and 12 hours. Decreasing values of creatine
      kinase-MB in the first tests after admission were only slightly less
      discriminating than increasing ones. At 12 to 24 hours after admission, the total
      creatine kinase as a value or slope, or the "relative index" (a ratio of the
      creatine kinase-MB in microgram/l [times 100] to the total creatine kinase) as a
      value or slope were inferior to creatine kinase-MB presentations. From the data
      for 44 patients with acute myocardial infarction and a known time of onset of
      symptoms, we were able to estimate an approximate onset time in patients where
      this was not available.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547433
TI  - An automated enzymatic inulin assay, capable of full sinistrin hydrolysis.
AB  - Renal inulin clearance remains the standard by which other methods of measuring
      glomerular filtration rate are judged. A fully automated enzymatic assay capable
      of use with linear configuration inulin was recently published (Summerfield AL,
      et al. Clin Chem 1993; 39:2333-7). Sinistrin, a readily soluble preparation of
      polyfructan with side branching, is more suitable for clinical use and far more
      widely used in Europe. By modifying the incubation phase of samples with
      inulinase, incorporating a kinetic modification to the method of fructose
      analysis, and increasing the buffer strengths, we report a fully automated
      system, with minimal sample prehandling capable of complete sinistrin hydrolysis,
      and adapted for use on the Cobas Mira.

PMID- 8547434
TI  - Influence of photoisomers in bilirubin determinations on Kodak Ektachem and
      Hitachi analysers in neonatal specimens study of the contribution of structural
      and configurational isomers.
AB  - We compared data obtained with the Kodak Ektachem and Hitachi 717 Analysers and
      HPLC from 83 neonates under phototherapy. Total bilirubin values determined with
      the Kodak and Hitachi are in good agreement, but we observed a large discrepancy
      in the results for conjugated (Kodak) and direct (Hitachi) bilirubin. HPLC
      revealed that all the samples contained configurational isomers, while only 7.7%
      and 30.8% contained conjugated bilirubin and structural isomers, respectively. We
      developed a device for the specific and quantitative production of
      configurational or structural isomers, by irradiation with blue or green light.
      In vitro, total bilirubin values are coherent for the routine analysers in the
      presence of configurational or structural isomers. With configurational isomers,
      unconjugated bilirubin (Kodak) is lower than total bilirubin (Kodak), and
      conjugated bilirubin (Kodak) is always equal to zero, so the apparatus gives a
      false positive response for delta bilirubin. In contrast, the direct bilirubin
      (Hitachi) is constant. Furthermore, in the presence of structural isomers,
      unconjugated bilirubin (Kodak) is unexpectedly higher than total bilirubin
      (Kodak), conjugated bilirubin (Kodak) is proportional to the quantity of these
      isomers, and direct bilirubin (Hitachi) is constant. The contribution of
      photoisomers in bilirubin measurements is discussed.

PMID- 8547435
TI  - Differences between enzymatic and diazo methods for measuring direct bilirubin.
AB  - An orthodox diazo method is popularly used for measuring bilirubin. On the other
      hand, an enzymatic method which employs bilirubin oxidase, has also been in use
      for considerable time. We have often found disparities between direct bilirubin
      values obtained with the enzymatic and the diazo methods. To determine the cause
      of these disparities, bilirubin subfractions were analysed and classified into
      two types by HPLC. Samples showing great differences contained conjugated,
      unconjugated and delta bilirubins (type I), while samples showing only small
      differences contained almost exclusively unconjugated bilirubin and delta
      bilirubin (type II). Conjugated bilirubin is therefore largely responsible for
      the differences observed between the two methods. Particularly marked differences
      were found for bile (in which all the bilirubin is conjugated) and for synthetic
      conjugated bilirubin. Bilirubin oxidase decreases the absorbance at 450 nm when
      it catalyses oxidation of bilirubin, but after the oxidation of synthetic
      conjugated bilirubin at pH 3.7 another peak appeared at 450 nm, as shown by HPLC
      and spectrophotometry, but not when the reaction was performed at pH 7.2, namely
      under conditions permitting complete oxidation. Incomplete oxidation products of
      conjugated bilirubin are responsible for the disparity. Care is therefore needed
      in the clinical interpretation of direct bilirubin values measured by the
      enzymatic method.

PMID- 8547436
TI  - Setting up and statistical evaluation of a new haemoglobin assay.
AB  - A new method for the determination of haemoglobin concentration in human whole
      blood has been devised. The assay takes advantage of the lysis of erythrocytes
      that occurs when blood penetrates the pores of a microporous membrane by a strong
      capillary effect. The released haemoglobin reacts with the reagents previously
      dried on the membrane, diffuses through the pores of the membrane and produces a
      uniform coloured spot whose reflectance at 556 nm can be evaluated at the side to
      that of application of the sample. In the experimental conditions used by
      authors, a linear relationship was obtained when the reciprocal reflectance was
      plotted against the haemoglobin concentration. Data obtained by the
      reflectometric method were compared with reference values on the same samples
      from centralized laboratories. Statistical analysis gave a correlation
      coefficient of 0.985 and only 4% of all haemoglobin determinations were outside
      the 95% confidence interval. No interference was observed by haematocrit,
      erythrocyte count, mean corpuscular volume or mean corpuscular haemoglobin
      concentration and leukocyte count. This method proved to be useful for rapid,
      accurate and precise assay of total haemoglobin on both capillary and venous
      blood.

PMID- 8547437
TI  - A simple, graphical method to evaluate laboratory assays.
AB  - Evaluation methods of laboratory assays often fail to predict the large,
      infrequent errors that are a major source of clinician complaints. We present a
      simple, graphical method to evaluate laboratory assays, which focuses on
      detecting large, infrequent errors. Our method, the folder empirical cumulative
      distribution plot or, more simply, mountain plot, is prepared by computing a
      percentile for each ranked difference between the new and reference method. To
      get a folded plot, one performs the following subtraction for all percentiles
      over 50: percentile = 100 - percentile. Percentiles (y axis) are then plotted
      against differences or percent differences (x axis). The calculations and plots
      are simple enough to perform in a spreadsheet. We also offer Windows based
      software to perform all calculations and plots. The mountain plot compared to the
      difference plot focuses attention on two features of the data: the center and the
      tails. We prefer the mountain plot over other graphical techniques because: 1. It
      is easier to find the central 95% of the data. 2. It is easier to estimate
      percentile for large differences (e.g., percentiles greater than 95%). 3. Unlike
      a histogram, the plot shape is not a function of the intervals. 4. Comparing
      different distributions is easier. 5. The plot is easier to interpret than a
      standard empirical cumulative distribution plot. Difference and mountain plots
      each provide complementary perspectives on the data. We recommend both plots.
      This method can also be used with data from a wide variety of other applications
      such as clinical trials and quality control.

PMID- 8547438
TI  - Determination of lactate, pyruvate, beta-hydroxybutyrate and acetoacetate with a
      centrifugal analyser.
AB  - Lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate are intermediary
      metabolites normally occurring in blood. Their relative concentrations are an
      expression of nutritional balance in energy metabolism. The simultaneous
      determination of these four analytes is of special interest in the understanding
      of energy homeostasis. Rapid, precise routine measurement of these four analytes
      is basic for the first orientation of the diagnosis of inborn errors of
      intermediary metabolism, especially those affecting fuel homeostasis. We describe
      an adaptation of the Cobas Fara II centrifugal analyser of some previously
      reported methods using the supernatant of a unique deproteinized blood sample for
      the determination of the four analytes. Reference values are calculated for a
      pediatric population. The difficulties involved in the diagnosis and follow-up of
      mitochondrial diseases in children require the standardization of analytical
      procedures for the correct interpretation of the results.

PMID- 8547439
TI  - Comparison of kits for the determination of creatine kinase activity in serum.
AB  - Thirteen kits from different suppliers for measurement of creatine kinase
      activity in human serum according to the IFCC recommendations were analyzed and
      compared. Concentrations of AMP, ADP, creatine phosphate, glucose, magnesium ion,
      NADP+, glucose-6-phosphate dehydrogenase, hexokinase and pH were measured in the
      reagents by various analytical techniques and compared with those recommended b
      the IFCC. We also compared by regression analysis the results of creatine kinase
      catalytic concentration obtained in human sera using commercial kits and in-house
      prepared reagents according tot he IFCC recommendation. Creatine kinase was also
      measured in a reference material using the different reagents. The overall
      results of the activity measurements and the composition of the majority of the
      kits agree well with one another and with the IFCC recommendation. Minor
      deviations were found in the evaluation of a few kits. One kit yielded creatine
      kinase activity values that were 17% lower. Results obtained in the reference
      material measurements showed differences with some kits which were not found
      using human sera.

PMID- 8547440
TI  - Evaluation of the COBAS CORE Immunoassay for measuring prostate-specific antigen
      (PSA)--multi-centre study results. The PSA Study Group.
AB  - Hoffmann-La Roche has introduced a fully automated COBAS CORE EIA for the
      measurement of prostate specific antigen (PSA). A regular and an ultrasensitive
      version of the assay are available. Both versions of the COBAS CORE PSA EIA were
      compared with the established IMx PSA assay from Abbott. Sera from 98 apparently
      healthy males, 224 patients with benign prostate hyperplasia, 17 patients with
      prostatitis and 111 patients with prostate cancer were determined using the COBAS
      CORE PSA EIA in comparison with the IMx PSA assay. The sera were drawn before
      treatment. Sera from 26 patients were also monitored through follow-up testing.
      The COBAS CORE analyser allows rapid analysis of large series of samples. Intra
      assay imprecision (CV) was between 1.7% and 4.9% (IMx PSA: between 2.4% and
      2.7%). The coefficient of variation for inter-assay imprecision was between 3.4%
      and 6.5% (IMx PSA: between 3.2% and 3.3%). The analytical detection limit was
      determined as 0.2 microgram/l for the regular COBAS CORE PSA EIA and 0.05
      microgram/l for the ultrasensitive version. A biological detection limit of 0.1
      microgram/l was determined for the ultrasensitive version. Results obtained using
      the COBAS CORE PSA EIA and IMx PSA assays were in excellent correlation:
      coefficient of correlation r = 0.99 and slope = 0.92, using prostate-specific
      antigen values from the complete study. Only in the measuring range below 10
      micrograms/l did the coefficients of correlation vary between 0.82 and
      0.93.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547441
TI  - Nonspecific abnormalities in psychiatry: do they reflect an ordered pathway of
      brain dysfunction?

PMID- 8547442
TI  - Cerebrospinal fluid neuropeptides in Alzheimer's disease and vascular dementia.
AB  - Cerebrospinal fluid (CSF) levels of several neuropeptides have been suggested as
      candidate markers in neurodegenerative disorders. We have examined the levels of
      corticotropin-releasing hormone (CRH), beta-endorphine (BEND), delta sleep
      inducing peptide (DSIP), somatostatin (SRIF), and neuropeptide Y (NPY) in CSF
      samples obtained under highly standardized conditions from healthy aged controls
      and from patients suffering from Alzheimer's disease (AD) or vascular dementia
      (VAD). The influence of some potentially confounding factors was evaluated. CRH
      and BEND were markedly decreased in both AD and VAD patients, and BEND levels
      correlated negatively with degree of dementia within the patient population. SRIF
      was decreased in both AD and VAD patients. DSIP was slightly increased in AD, but
      not in VAD. NPY did not differ between groups. For none of the peptides did CSF
      concentrations correlate significantly with duration of illness, nor, with the
      exception of BEND, with its degree. Present data do not support the hypothesis
      that specific neuropeptide changes occur in different neurodegenerative
      disorders, but are in agreement with previous reports suggesting that
      neuropeptide systems are differentially affected by neurodegeneration.

PMID- 8547443
TI  - Immunoglobulin production in vitro in major depression: a pilot study on the
      modulating action of endogenous cortisol.
AB  - To investigate the possible differential sensitivity of hydrocortisone (HCO) on
      immunoglobulin (Ig) production in depression in relation to endogenous cortisol
      levels, blood was obtained at 8 AM and 4 PM from 10 inpatients with major
      depression according to DSM-III-R criteria and 10 age- and sex-matched healthy
      subjects. Peripheral blood lymphocytes were cultured in the presence of graded
      concentrations (10(-9)-10(-5) M) of HCO to study the effect on immunoglobulin
      (IgG and IgM) synthesis. In addition, peripheral blood lymphocytes were cultured
      in the presence of pokeweed mitogen (PWM) to study any additional effect of
      graded concentrations of HCO (10(-9)-10(-5) M) on IgG and IgM synthesis. Mean
      plasma cortisol levels at both time points were higher in patients compared to
      controls. HCO--preferentially at concentrations of 10(-8)-10(-6) molar-
      stimulated IgG and IgM production in controls, except for IgM production in the 8
      AM samples, when the cells were cultured in the absence of PWM. Under these
      culture conditions, HCO stimulated IgG but not IgM synthesis in depressed
      patients. PWM-driven IgG and IgM synthesis in controls was stimulated by HCO in
      both the 8 AM and the 4 PM samples. In patients PWM driven IgG synthesis was
      stimulated by HCO in the 8 AM but not in the 4 PM samples. PWM-stimulated IgM
      synthesis was not augmented by HCO in depressed patients. We conclude that a
      differential sensitivity to the effects of HCO exists in in vitro IgG and IgM
      synthesis between depressed patients and controls. Furthermore, we suggest that
      immunocompetent cells of depressed patients possess corticosteroid-resistant
      properties.

PMID- 8547444
TI  - Polyamines and their metabolizing enzymes in human frontal cortex and
      hippocampus: preliminary measurements in affective disorders.
AB  - Affective disorders are associated with maladaptive response to stressful life
      events. Based on the observation that a transient increase in brain polyamine
      metabolism is a common response to stressful stimuli, our hypothesis is that a
      maladaptive polyamine stress response may be involved in the pathophysiology of
      affective disorders. Our current research efforts, therefore, concentrate on the
      characterization of this PA response, and on its pharmacological regulation. The
      present preliminary study is the first to measure the polyamines, putrescine,
      spermidine, and spermine, and their metabolizing enzymes, ornithine
      decarboxylase, S-adenosylmethionine decarboxylase, and spermidine/spermine N1
      acetyltransferase, in brain autopsy samples from people who suffered from
      depressive disorders or schizophrenia, or from those who committed suicide. The
      data of affected individuals did not reveal significant differences when compared
      to those of suicide cases, or to those of people with no known neurologic or
      psychiatric abnormalities. The following regional differences were observed:
      spermidine concentrations and ornithine decarboxylase activity were higher, but S
      adenosylmethionine decarboxylase activity was lower in the hippocampus as
      compared to the frontal cortex. Preliminary studies with rat brain indicate that
      an increase in polyamine metabolizing enzyme activities occurs within several
      hours after death and persists for at least 48 hours. These observations, in
      turn, indicate that earlier autopsies are crucial for detection of changes in
      polyamine metabolism. We conclude that further studies to test the polyamine
      hypothesis are warranted.

PMID- 8547445
TI  - Prolactin response to buspirone challenge in the presence of dopaminergic
      blockade.
AB  - Buspirone-stimulated prolactin release has been employed as an indirect measure
      of central serotonin activity; however, it is not clear whether serotonergic or
      dopaminergic systems are responsible for this response. In an attempt to further
      elucidate the mechanism, we studied the prolactin response to buspirone in eight
      subjects in the presence of maximal dopaminergic receptor blockade with
      metoclopramide under placebo-controlled, double-blind conditions. The prolactin
      response to buspirone in the presence of metoclopramide was not statistically
      different from that to placebo under the same conditions. The demonstration of
      further prolactin release by a bolus of thyrotropin-releasing hormone under
      maximal dopaminergic receptor blockade provided evidence against potential
      pituitary prolactin depletion by metoclopramide. These results lend further
      support to a dopaminergic mechanism in buspirone-induced prolactin secretion;
      therefore, further caution is warranted in interpreting the results of this
      challenge test as a measure of serotonergic activity in the brain.

PMID- 8547446
TI  - Rebreathing tests in panic disorder.
AB  - In order to compare the ventilatory response of panic patients and normal
      controls, 21 panic disorder patients with agoraphobia and 21 normal controls
      underwent the Read rebreathing test. Panic patients panicked significantly more
      during the test, responded with more respiratory rate and less tidal volume, but
      showed no hypersensitivity to inhaled carbon dioxide compared to normal controls.

PMID- 8547447
TI  - Monosialoganglioside cotreatment prevents haloperidol treatment-associated loss
      of cholinergic enzymes in rat brain.
AB  - Effects of monosialoganglioside (GM1 ganglioside) cotreatment with haloperidol
      (HAL) were studied in rat on the haloperidol treatment-associated changes in
      cholinergic enzymes, choline acetyltransferase (ChAT), and acetylcholinesterase
      (AChE) in three brain regions of interest: striatum, hippocampus, and cerebral
      cortex. Short-term (8 days) haloperidol treatment significantly increased the
      levels of both ChAT and AChE in all the three regions of brain, as compared with
      controls (for ChAT: p < .0001 for all comparisons, and for AChE: striatum: p <
      .0001; hippocampus: p < .0003; cortex: p < .05). Cotreatment with GM1 ganglioside
      further increased the ChAT activity relative to haloperidol treatment alone in
      all three regions (p < .05). The AChE activity was also significantly higher than
      controls in all three regions (p < .05 for all comparisons) and higher than
      haloperidol treatment only in hippocampus (p < .02). After chronic haloperidol
      treatment (45 days), ChAT activity in cortex had returned to control values in
      both HAL and HAL + GM1 groups, with no significant group differences remaining (p
      = .10). By contrast, relative to control values, HAL and HAL + GM1 groups both
      showed lower ChAT activity in the striatum, as well as in the hippocampus (p <
      .0001 for both), with significantly lower ChAT activity in the HAL than in the
      HAL + GM1 group for both areas (p = < .0001 for both). AChE activity showed a
      significant difference only between the HAL and HAL + GM1 groups in the cortex (p
      = .003), but no significant effects of group were seen on AChE activity in either
      striatum or hippocampus. These data suggest that the protective effects of GM1
      ganglioside cotreatment on haloperidol-induced alterations in cholinergic systems
      can be relevant for protecting against the complications of neuroleptic-induced
      parkinsonism.

PMID- 8547448
TI  - Prefrontal cortical and hippocampal modulation of haloperidol-induced catalepsy
      and apomorphine-induced stereotypic behaviors in the rat.
AB  - Effects of prefrontal cortical or hippocampal excitotoxic lesions on behavioral
      parameters related to dopaminergic transmission in the basal ganglia were
      investigated in the rat. We examined haloperidol-induced catalepsy and
      apomorphine-induced stereotypic behaviors after ibotenic acid lesions of the
      medial prefrontal cortex (MPFC), dorsal (DH), or ventral hippocampus (VH) in
      adult rats. Haloperidol-induced (1 mg/kg) catalepsy was decreased in rats with
      either MPFC or VH but not DH lesions. While both DH and VH lesioned animals
      demonstrated a reduction in apomorphine-induced (0.75 mg/kg) stereotypic
      behaviors, the VH lesioned animals also showed an enhancement of locomotor
      activity. MPFC lesioned rats tended towards potentiation of stereotypic behaviors
      and reduced locomotion after apomorphine administration. These data indicate that
      loss of prefrontal cortical or hippocampal modulation leads to an enhancement of
      DA transmission within the basal ganglia, though the pattern of augmentation
      depends on the area lesioned.

PMID- 8547449
TI  - Effects of cocaine on D3 and D4 receptor expression in the human striatum.

PMID- 8547450
TI  - Plasma prolactin and plasma homovanillic acid: predictors of clinical response in
      schizophrenia.

PMID- 8547451
TI  - Affective disorders in Holland after prenatal exposure to the 1957 A2 influenza
      epidemic.

PMID- 8547452
TI  - Serotonin-induced platelet calcium mobilization is enhanced in bulimia nervosa
      but not in anorexia nervosa.

PMID- 8547453
TI  - Sexual dimorphism in the brain: it's worse than you thought.

PMID- 8547454
TI  - A prospective follow-up study of brain morphology and cognition in first-episode
      schizophrenic patients: preliminary findings.
AB  - Brain morphological abnormalities have been reported in several independent
      investigations of chronic schizophrenic patients. The present study is a
      prospective 4-year follow-up of first-episode schizophrenic patients to determine
      whether some of these abnormalities may be a consequence of regional brain
      structural change over time after the onset of a first psychotic episode. Whole
      hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus
      callosum, and lateral ventricles were measured in a series of MRI scans taken
      over a 4-year period in 20 patients and five controls. Total volume reduction was
      noted in both hemispheres to a greater degree in patients than controls. When
      adjusted for total brain size, left ventricular enlargement occurred in patients,
      but not controls, over time. These preliminary data suggest that subtle cortical
      atrophy may be occurring over time after the onset of illness.

PMID- 8547455
TI  - Platelet monoamine oxidase activity levels in subgroups of alcoholics:
      diagnostic, temporal, and clinical correlates.
AB  - Platelet monoamine oxidase (MAO) activity levels were measured in 47 male
      inpatient alcoholics to determine whether this biological marker might be useful
      in differentiating subtypes of alcoholics. Of the subgrouping methods tested,
      only type 2 alcoholics defined by the criteria of Gilligan et al had
      significantly lower platelet MAO activity than type 1 alcoholics at intake, but
      this finding was not stable over time in a subset of subjects. Neither separating
      male veteran alcoholics into either of two other variations of the type 1/type 2
      subtypes, nor classifying the sample into primary alcoholics versus primary ASPD
      with secondary alcoholism categories, yielded significant differences between
      subgroups. Generally, enzyme activity levels (Vmax) were higher about 10 days
      after stopping drinking compared to platelet MAO values determined in
      thrombocytes obtained after approximately 4 weeks abstinence; these levels
      remained relatively stable 3 months later in a cohort of subjects. Tobacco
      smoking was significantly negatively correlated to platelet MAO activity levels.

PMID- 8547456
TI  - Menstrual phase-independent retrieval deficit in women with PMS.
AB  - Memory and attention were evaluated in 19 women with prospectively documented
      premenstrual syndrome (PMS) and 17 women without PMS. Testing occurred during the
      late luteal and follicular phases of the menstrual cycle. Estrogen, progesterone,
      and FSH levels were obtained on testing days for 23 of the women, while mood
      measures were obtained for all of the women. Repeated measures analysis of
      variance yielded significant group differences on recall measures, with no
      differences noted on recognition indices. No significant session or interaction
      effects were observed. This pattern of results suggests impaired retrieval of
      learned information coincident with intact encoding. No significant effects were
      noted for any of the nonverbal memory, attention, or other neurocognitive
      variables. The obtained data support previous findings of a mild, phase
      independent memory impairment in women with PMS and also contribute to a better
      understanding of the component memory processes involved.

PMID- 8547457
TI  - Fear-potentiated startle in posttraumatic stress disorder.
AB  - Exaggerated startle is reputed to be one of the cardinal symptoms of
      posttraumatic stress disorder (PTSD); however, objective studies have given
      conflicting results as to whether or not startle is increased in PTSD. The
      present study investigated startle in PTSD during the threat of shock (fear
      potentiated startle). The eyeblink component of the startle reflex was measured
      at various times preceding and following the anticipation of unpleasant electric
      shocks in 9 PTSD subjects and 10 age-matched, healthy controls. Startle amplitude
      was significantly greater during baseline and during shock anticipation in the
      PTSD subjects, compared to the controls. Habituation of the startle reflex was
      normal. Because other studies in the literature, as well as in our own
      laboratory, have failed to find exaggerated startle at baseline (i.e., absence of
      stress) in PTSD patients, it is unlikely that the present results reflect a
      chronic elevation of startle in this group. Instead, the higher levels of startle
      in the PTSD group probably resulted from a greater conditioned emotional response
      in this group, triggered by anticipation of electric shocks that generalized to
      the unfamiliar experimental context in which testing occurred. Hence, emotionally
      charged test procedures may be especially informative in distinguishing PTSD
      patients from other psychiatric diagnostic groups.

PMID- 8547458
TI  - Behavioral laterality in individuals with Gilles de la Tourette's syndrome and
      basal ganglia alterations: a preliminary report.
AB  - This study aims to investigate whether abnormalities in structural basal ganglia
      asymmetries in Tourette's syndrome (GTS) have functional significance. Eleven
      adult GTS patients and 11 normal controls who had participated in the previous
      MRI study where GTS patients lacked the normal left-greater-than-right (L > R)
      lenticular asymmetry were re-recruited. They were administered a battery of
      lateralizing neuropsychological tasks believed to require intact basal ganglia
      function. GTS subjects lacked normal functional asymmetries on these measures, as
      predicted. The neuropsychological measures also accounted for a significant
      portion of the variance in the severity of tic symptoms. These findings suggest
      that GTS subjects who lack normal basal ganglia structural asymmetries also lack
      normal functional asymmetries on related neuropsychological measures.

PMID- 8547459
TI  - Sleep research in depressive illness: clinical implications--a tasting menu.
AB  - It is well established that sleep patterns are altered in psychiatric disorders
      and represent a very common presenting complaint. Even though sleep disturbance
      is often a key feature of many psychiatric conditions, its most prominent role
      has been in mood disorders. The clinical implications of disordered sleep in mood
      disorders represent the focus for this paper. Specifically, the following
      questions will be discussed: (1) How sensitive and specific are the sleep
      findings in depressive disorders? (2) What are the characteristics of sleep in
      depression and subtypes of depression? (3) Are sleep changes in depression
      episodic (state-like) or persistent (trait-like)? As we point to specific
      characteristics of sleep in subtypes, it is important to note that more
      sophisticated analyses of sleep measures provide an opportunity to pinpoint
      changes between delusional/nondelusional depression or endogenous/nonendogenous
      depression. Furthermore, differences among subtypes will be best understood if we
      realize that both age and gender affect sleep measures in a consistent manner.
      Therefore, for example, there is a more robust separation between patients and
      controls in older individuals than in younger individuals.

PMID- 8547460
TI  - Vulnerability to fluoxetine-induced indifference syndrome among opiate addicts: a
      case report.

PMID- 8547461
TI  - Clomipramine efficacy for Tourette syndrome and major depression: a case study.

PMID- 8547462
TI  - Prior antidepressant treatment does not have an impact on response to desipramine
      treatment in major depression.

PMID- 8547463
TI  - No difference in the effect of biperiden and amantadine on negative symptoms in
      medicated chronic schizophrenic patients.

PMID- 8547464
TI  - Dopamine uptake in platelets.

PMID- 8547465
TI  - Prolactin is synthesized and secreted by the endometrium.

PMID- 8547466
TI  - Diverse testicular responses to exogenous growth hormone and follicle-stimulating
      hormone in prepubertal boars.
AB  - The effects of exogenous growth hormone (GH) and FSH on development of the testes
      in intact prepubertal boars was investigated. Twenty-four boars received one of
      four daily treatments from 8 through 40 days of age: 1) 90 micrograms porcine (p)
      GH/kg body weight (BW), 2) 100 micrograms pFSH/kg BW, 3) GH + FSH, or 4) vehicle
      only (control). Plasma testosterone levels, measured at 10-day intervals, were
      similar among groups of boars throughout the study. Body weights among groups
      were similar during treatment, and testicular weight between treatment groups did
      not differ at castration (100 days of age). However, total length of the
      seminiferous tubule per testis in FSH-treated boars was 59% greater than in GH
      treated animals (2705 vs. 1704 m; p < 0.05). Diameter of the tubule in GH-treated
      boars was 58% greater than in FSH-treated boars (p = 0.03). Relative mass of
      spermatocytes and spermatids in GH-treated animals exceeded that in controls by
      2.5-fold and that in FSH boars by 75-fold (p = 0.05). There were no differences
      in effects of GH + FSH treatment as compared to control treatment; none of the
      treatments affected any interstitial tissue parameter measured. These results
      suggest that exogenous FSH had a mitogenic effect on Sertoli cells while delaying
      tubular maturity, whereas exogenous GH promoted tubular and Sertoli cell
      maturation, defined as increased Sertoli cell size, lumen formation, and onset of
      spermatogenesis.

PMID- 8547467
TI  - Granulosa cell modulation of luteinizing hormone-dependent androgen production by
      ovarian theca-interstitial cells: a temporal switch from suppression to
      augmentation stimulated by follicle-stimulating hormone in vitro.
AB  - The production of estradiol-17 beta (E2) by granulosa cells (GC) of the dominant
      follicle is dependent upon LH-stimulated synthesis of androgens by ovarian theca
      interstitial cells (TIC). Recent evidence has pointed toward an intrafollicular
      paracrine system, regulated by FSH and involving GC, that may modulate the LH
      dependent production of androgens by TIC. In the present study, the role of GC
      and FSH in modulating LH-dependent TIC and androsterone production was examined.
      In cultures of dispersed whole ovarian cells (containing populations of both GC
      and TIC) from intact immature rats, LH stimulated a 10-fold increase in
      androsterone production (maximum androsterone = 21.0 +/- 1.1 ng/ml). By
      comparison, androsterone production was increased 50-fold in LH-stimulated
      cultures of dispersed whole ovarian cells from hypophysectomized immature rats
      (108 +/- 18 ng androsterone/ml). The EC50 for LH (0.02 +/- 0.001 ng/ml) was
      identical in the two cell preparations. We hypothesized that the lesser androgen
      production by whole ovarian cell cultures from intact rats was due to suppression
      by the GC. To investigate the role of GC in modulating TIC androgen production,
      highly purified TIC from immature hypophysectomized rats were cultured in the
      presence of GC obtained from intact immature rats. Increasing numbers of GC (2.5
      100 x 10(3) GC per well) caused a progressive decrease in LH-dependent
      androsterone production by TIC. Additionally, LH-dependent androsterone
      production was suppressed by the conditioned medium from recombinant human FSH
      (rFSH)-stimulated GC (54% of the value for LH-stimulated TIC controls),
      indicating the involvement of a GC-secreted paracrine factor or factors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8547468
TI  - Inositol trisphosphate-induced calcium release in the generation of calcium
      oscillations in bovine eggs.
AB  - Bovine eggs exhibit repetitive rises in intracellular calcium concentration
      ([Ca2+]i) in response to fertilization. The signaling pathways and Ca2 release
      mechanisms involved in their generation are not well characterized. This study
      examined the presence of a GTP-binding protein (G-protein) signaling pathway as
      well as the role of inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R)
      mediated Ca2+ release and ryanodine receptor (RyR)-mediated Ca2+ release, the two
      Ca2+ receptors/channels most often thought to participate in the generation of
      [Ca2+]i oscillations, by injecting appropriate agonists and antagonists and
      monitoring their effects on Ca2+ release and pronucleus formation, injection of
      guanosine 5'-0-(3-thiotriphosphate) (GTP gamma [S]), which promotes G-protein
      mediated phosphoinositide turnover, induced, at high concentrations, repetitive
      [Ca2+]i rises. Low concentrations of GTP gamma [S] were ineffective. Injection of
      inositol trisphosphorothioate (InsP3S3), a nonmetabolizable analogue of InsP3,
      evoked an immediate Ca2+ release followed by [Ca2R]i oscillations. The GTP gamma
      [S]- and InsP3S3-induced oscillations showed a rapid attenuation in amplitude and
      were terminated in about 30-60 min. Thimerosal, a thiol oxidizing agent, caused
      repetitive rises in [Ca2+]i by sensitizing Ca2+ injection-induced Ca2+ release.
      Injection of ryanodine, which stimulates Ca(2+)-induced Ca2+ release via the RyR,
      did not induce [Ca2+]i oscillations; and eggs into which it was preinjected
      exhibited normal [Ca2+]i oscillations in response to thimerosal. Preinjection of
      heparin, a competitive InsP3R antagonist, blocked in a dose-dependent manner the
      Ca2+ response to InsP3 and thimerosal, and its injection into fertilized
      oscillating eggs inhibited [Ca2+]i oscillations in all eggs.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8547469
TI  - Gonadotropin-releasing hormone agonist suppression of ovarian tumorigenesis in
      mice of the Wx/Wv genotype.
AB  - Although many investigations have shown a correlation between elevated
      gonadotropin levels and ovarian tumors (the gonadotropin theory), the ovarian
      response to a specific suppression of the gonadotropins has not been elucidated.
      The ovaries of (C57BL/6J x C3H/HeJ)F1-Wx/Wv mice, which contain 1% of the normal
      oocyte count at birth, rapidly lose the follicular apparatus and develop a 100%
      incidence of bilateral complex tubular adenomas from the surface germinal
      epithelium, which is also the origin of 90% of human ovarian carcinomas. Plasma
      levels of LH and FSH are known to rise fourfold during the period of
      tumorigenesis. We compared tumor development in Wx/Wv mice after either injecting
      a GnRH agonist (3.6 mg slow-release goserelin depot, Zoladex Depot) or
      administering a sham injection every 28 days from the age of 7 days up to 245
      days. All 15 Wx/Wv mice that received sham injections developed bilateral ovarian
      tubular adenomas from the surface germinal epithelium. In none of the 11 mice
      receiving the GnRH agonist was any tumor found (p < 0.00005), and a significant
      suppression of the gonadotropins was demonstrated (p < 0.00005).

PMID- 8547470
TI  - Cytogenetical analysis and developmental potential of vitrified mouse oocytes.
AB  - Mature mouse oocytes were cryopreserved by vitrification in 6 M dimethyl
      sulfoxide (VS). After warming they were either artificially activated with
      strontium (Sr2+), and the incidence of chromosome non-disjunction was assessed at
      first cleavage metaphase; or they were fertilized in vitro, and postimplantation
      survival was examined at Day 15 of gestation. Similar proportions of vitrified
      and freshly collected oocytes were activated with Sr2+ (75% and 82%,
      respectively). The majority of activated oocytes extruded the second polar body
      and formed a single pronucleus ( > 90%). When the exposure time to VS was
      increased from 90 to 110 sec without cooling, a significant proportion of
      activated oocytes arrested at the pronuclear stage (30%), and chromosome
      condensation did not occur. The frequency of aneuploidy in vitrified and control
      oocytes was similar, but when exposure to VS without cooling was extended,
      aneuploidy and second polar body retention were significantly higher than those
      of controls (p < 0.05). The rates of fertilization of vitrified (85%) and control
      oocytes (92%) did not differ. After transfer, similar proportions of vitrified
      and control embryos implanted (68-80%) and formed normal fetuses (38-49%). We
      conclude that vitrification in 6 M dimethyl sulfoxide is a simple and safe
      procedure for the preservation of mouse oocytes provided that the time of
      exposure to the cryoprotectant is carefully controlled.

PMID- 8547471
TI  - Development of bovine embryos in KSOM with added superoxide dismutase and taurine
      and with five and twenty percent O2.
AB  - To further define requirements for embryo development without the assistance of
      complex media, serum, or coculture, the effects of 5% and 20% O2 concentrations,
      superoxide dismutase (SOD) (experiment 1), and taurine (experiment 2) were tested
      in a single culture medium (KSOM modified with 2.5 mM HEPES). Bovine embryos were
      produced in vitro maturation (IVM) and in vitro fertilization (IVF) of oocytes.
      After fertilization, embryos were cultured in 5% O2:5% CO2:90% N2 at 30 degrees C
      for the first 40-44 h; then embryos with 4 to 8 cells were cultured in different
      treatments for another 6 days. Percentage development subsequently was based on
      this number. In experiment 1, more blastocysts were produced in 5% O2:5% CO2:90%
      N2 (37%) than in 20% O2:5% CO2:75% N2 (18%; p < 0.01). Blastocyst development
      with 0, 300, and 600 U/ml of SOD, respectively, was 26%, 26%, and 30% (p > 0.05).
      In experiment 2, more blastocysts were formed in 5% O2 (39%) than in 95% air
      (30%; p < 0.05). Also, with 20% O2 and 0, 7, and 14 mM taurine in the medium,
      blastocyst formation was 18%, 35%, and 36% (p < 0.05). However, in 5% O2, 7 and
      14 mM taurine was not beneficial (p = 0.99), as 39% blastocysts were formed with
      no taurine. In conclusion, results from both experiments demonstrated that 5% O2
      was superior to 20% O2 for development of IVM/IVF bovine embryos. SOD had no
      effect in either 5% or 20% O2. However, 7 mM and 14 mM taurine counteracted the
      negative effect of 20% O2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547472
TI  - Angiotensin II interferes with steroidogenesis in porcine granulosa cells.
AB  - The elements for the synthesis and activity of the vasopressor angiotensin II
      (AII) are present in the mammalian ovary. In the present investigation, the
      effects of AII were determined on three parameters of steroidogenic function in
      porcine granulosa cells in vitro: the accumulation of progesterone, the cellular
      content of the enzyme 3 beta-hydroxysteroid dehydrogenase delta 5-4 isomerase (3
      beta-HSD), and the accumulation of mRNA for 3 beta-HSD. Cells were incubated with
      LH (200 ng/ml) in the presence or absence of AII (10(-7) M) or phorbol 12
      myristate 13-acetate (PMA, 10(-7) M); doses of AII from 10(-10) to 10(-6) M in
      the presence or absence of LH; the AII reactor antagonist saralasin (10(-6) M) in
      the presence of AII or in combination of AII and LH; and AII in the presence or
      absence of (Bu)2 cAMP. The results demonstrate that LH increased progesterone, 3
      beta-HSD message, and 3 beta-HSD content. Both PMA and AII interfered with the LH
      induced progesterone accumulation, reducing the response by 50% or more. All also
      abrogated the LH-induced increases in 3 beta-HSD mRNA and 3 beta-HSD enzyme
      content in porcine granulosa cells. The AII inhibition was dose-dependent. The
      AII receptor antagonist saralasin blocked the inhibitory effects of AII on LH
      induced steroidogenic events. AII interfered with the (Bu)2 cAMP induction of
      steroidogenesis and 3 beta-HSD mRNA and enzyme accumulation when (Bu)2 cAMP was
      present at a concentration of 30 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547473
TI  - Metalloproteinase activity has a role in equine chorionic girdle cell invasion.
AB  - Chorionic girdle cells are a highly invasive subpopulation of trophoblast cells
      of the equine conceptus. By Day 35 (Day 0 = day of ovulation), cells of the
      chorionic girdle adhere to the uterine epithelium and begin to invade the
      endometrial wall. Invasive cells must attach to extracellular matrix proteins,
      secrete proteinases capable of degrading matrix, and migrate through the degraded
      matrix; invasion is largely dependent on the proteinase activity of the cells.
      The objective, therefore, was to develop an in vitro system to examine the
      mechanisms of equine chorionic girdle cell invasion through extracellular matrix.
      Day 34 chorionic girdle cell preparations were cultured on Matrigel Invasion
      Chambers. The cultured invasive cells were binucleate with prominent nucleoli and
      were often highly vacuolated, consistent with in vivo cup cell morphology. In
      addition, the cultured cells produced eCG. Additional Day 34 chorionic girdle
      cell preparations were cultured on Matrigel Invasion Chambers with or without
      proteinase inhibitors (aprotinin, bestatin, 1,10-phenanthroline) to determine the
      proteinase activity associated with girdle cell invasion. Only the
      metalloproteinase inhibitor, 1,10-phenanthroline, inhibited chorionic girdle cell
      invasion through Matrigel. Chorionic girdle cell supernatants were characterized
      by zymography, and the proteinases produced by these cells were confirmed to be
      metalloproteinases at approximate molecular masses of 72 and 95 kDa. The results
      indicated that equine chorionic girdle cells have matrix-degrading capabilities
      through metalloproteinase activity. Similar metalloproteinase activity has been
      reported to be necessary for mouse and human trophoblast invasion, suggesting a
      similar mechanism of implantation.

PMID- 8547474
TI  - Hormonal induction of ovulation stimulates atresia of antral follicles in gilts.
AB  - Two breeds of prepubertal gilts known to differ in their ovarian development were
      used to compare the effect of hormonally stimulated ovulation on follicle numbers
      and proportion of follicular atresia in size classes other than preovulatory
      follicles. Hormonal treatments (hCG or eCG-hCG) were given to Meishan gilts (n =
      36) at 3, 2, and 1 standard deviations (SD) before the mean age of puberty (51,
      64, and 77 days of age) and to Large White gilts (n = 24) at 3 and 1 SD before
      the mean age of puberty (140 and 166 days of age). Ovarian follicle populations
      determined in the right ovaries 18 h after hCG injection alone (hCG) or 72 h
      after eCG injection (eCG-hCG) were compared with those in the left ovaries, which
      had been removed prior to injections. Follicles with dispersed cumulus cells
      around the oocytes (expected ovulations) observed after hormonal treatments
      (right ovaries) were considered for follicular measures and categorized into
      specific size classes according to their diameter. Human CG alone did not affect
      any follicular parameters measured at any age in either of the two breeds
      studied. The overall population of nonatretic follicles was significantly reduced
      by the eCFG-hCG treatment in the Large White breed when imposed at either 3 or 1
      SD before the mean age of puberty (262.6 vs. 158.8; p < 0.01). Among the various
      follicle size classes studied, eCG-hCG treatment significantly decreased the mean
      number of follicles in size classes 2 (1.13-2.00 mm in diameter) and 3 (2.01-3.56
      mm in diameter) at either 3 or 1 SD before the mean age of puberty in the Large
      White gilts (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547475
TI  - Stress-induced murine abortion associated with substance P-dependent alteration
      in cytokines in maternal uterine decidua.
AB  - Stress is known to induce abortions, but underlying mechanisms are unknown. Both
      alloimmunization and injection of antibody to the asialoGM1 determinant of
      natural killer cells have been shown to prevent stress-triggered abortion in
      mice. DBA/2J-mated CBA/J female mice were used to investigate the influence of
      stress during early gestation on systemic hormone levels and on cytokines in the
      decidua that are thought to be relevant to abortion in nonstress-related murine
      abortion. Lowered levels of progesterone did not occur as a result of stress. In
      stressed mice, increased levels of the abortogenic cytokine tumor necrosis factor
      alpha (TNF alpha) were associated with decreased levels of pregnancy-protective
      transforming growth factor beta 2-related suppressive activity in uterine
      decidua. In the alloimmunized animals where stress failed to boost the abortion
      rate, these effects were abrogated. Production of TNF alpha may be stimulated by
      the neurotransmitter substance P (SP); after injection of an SP receptor
      antagonist or SP-antibody, stress failed to increase the abortion rate above the
      background level. The increased levels of TNF alpha we observed in the stressed
      animals were completely abrogated in the animals that had received the SP
      receptor antagonist; stress also failed to decrease the pregnancy-protective
      suppressive activity in the decidua of these animals. The data indicate that
      stress may inhibit protective suppressor mechanisms and promote secretion of
      abortogenic cytokines such as TNF alpha via neurotransmitter SP.

PMID- 8547476
TI  - Stage-specific distribution of the spermatid-specific histone 2B in the rat
      testis.
AB  - Male germ cells contain a number of histone variants, most of which are
      synthesized during either the mitotic or the meiotic stages of spermatogenesis. A
      spermatid-specific H2B (ssH2B) variant has been identified in mouse round
      spermatids that has an additional 12 amino acids at its carboxyl terminus as
      compared to somatic H2Bs. Until now, the presence of this protein in other
      mammals has not been known. Northern blot analysis using an oligonucleotide probe
      complementary to a unique coding region of the C-terminus of mouse ssH2B showed
      that mRNA encoding this protein was present in isolated rat round spermatids.
      Furthermore, immunoblot analysis of basic nuclear proteins from round spermatids
      probed with an anti-ssH2B antiserum that recognizes the novel peptide sequence
      indicated that the protein was present in round spermatids but not in pachytene
      spermatocytes. The ssH2B comigrated with H2A.X by acid-urea (2.5 M) PAGE and
      migrated slightly more slowly than TH2B by acid-urea-Triton PAGE. When
      seminiferous tubules were microdissected stage-specifically and basic nuclear
      proteins were immunoblotted, ssH2B was detected in tubule sections of stages II
      VI. It reached a maximum level in stages VII-VIII and then decreased to minimal
      levels in stages XIII-I. Since ssH2B was not detected in pachytene spermatocytes,
      the stage-specific levels of ssH2B corresponded to the respective steps of
      spermatids present in the tubules. While ssH2B constituted a relatively small
      amount (approximately 2%) of total H2B protein in round spermatids, its presence
      in both the mouse and the rat suggests that its function may be conserved in
      mammalian spermatogenic cells.

PMID- 8547477
TI  - Changes in uterine estrogen and progesterone receptors during delayed
      implantation and early implantation in the spotted skunk.
AB  - Although the exact cause(s) of embryonic diapause in the western spotted skunk
      and other carnivores remains unknown, it has been hypothesized that it may be due
      to levels of ovarian hormone secretion that are insufficient to promote a uterine
      environment conducive to continuous embryonic development and implantation.
      Immunocytochemistry was used to determine whether changes in abundance or
      distribution of estrogen receptors (ER) and progesterone receptors (PR) may be
      associated with the cessation or renewal of embryonic development. Thirty
      pregnant skunks were killed during delayed implantation and periimplantation
      periods. ER and PR were detected in luminal and glandular epithelium, endometrial
      stroma, vasculature, and myometrium of the uterus during the period of delayed
      implantation. There was a significant reduction of both ER and PR receptors
      during the periimplantation period. The most pronounced change was the complete
      loss or reduction in staining intensity for PR and ER in the luminal epithelium
      during the first 2-3 days after implantation. These findings suggest that the
      failure of skunk blastocysts to undergo continuous development and implant
      without a prolonged period of diapause is not the result of an insufficient
      number of ER or PR in the uterus. The data also indicate that renewed embryonic
      development and implantation is not associated with an increase in these uterine
      steroid receptors.

PMID- 8547478
TI  - Patterns of relaxin and steroids in the reproductive cycle of the common marmoset
      (Callithrix jacchus): effects of prostaglandin F2 alpha on relaxin and
      progesterone secretion during pregnancy.
AB  - We measured the concentrations of relaxin (Rlx), progesterone, and estradiol-17
      beta in serum samples obtained twice or three times weekly from marmosets during
      the estrous cycle and pregnancy. The cyclic patterns and concentrations of
      progesterone and estradiol-17 beta were similar to those reported by previous
      investigators. Rlx was not detected in individual serum samples ( < 0.62-1.25
      ng/ml) obtained from nonpregnant marmosets. However, pooling of luteal serum from
      all animals permitted assay of much larger volumes of serum (0.4 ml vs. 0.1 ml),
      and a concentration of about 1 ng/ml was detected. Rlx was first detected in
      serum in the second or third week of the 21-wk marmoset pregnancy, rose to a peak
      during Weeks 10-14, and then declined slowly as the time of parturition
      approached. The pattern of Rlx was unlike that observed during pregnancy in Old
      World monkeys, chimpanzees, or women, and resembled, instead, that seen in
      rodents, carnivores, and equids. Progesterone and estradiol-17 beta likewise
      increased throughout pregnancy, and their patterns were similar to those
      previously described for marmosets by other investigators. The concentrations of
      the steroids and Rlx in serum of pregnant marmosets was 10-fold or more higher
      than those found in Old World monkeys, baboons, chimpanzees, or women.
      Spontaneous abortions in two of the marmosets were accompanied by precipitous
      falls in serum levels of progesterone, estradiol-17 beta, and Rlx. Following s.c.
      injection of the luteolytic agent prostaglandin F2 alpha (PGF2 alpha) into two
      marmosets at midpregnancy, serum progesterone and Rlx fell to low levels. These
      animals received a progestin, 17 alpha-ethyl-19-nortesterone, to preclude
      abortion. Serum progesterone rose again, but serum Rlx remained low for the
      duration of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547479
TI  - Expression of vav proto-oncogene by nonhematopoietic trophoblast cells at the
      human uteroplacental interface.
AB  - Vav is a signal transducing molecule containing SH2 and SH3 domains and a guanine
      nucleotide releasing factor-like domain. Its expression is thought to be highly
      specific for hematopoietic cells. Here we describe the expression of vav
      transcripts in human nonhematopoietic trophoblasts. By northern blotting,
      expression of 2.8-kb vav mRNA was detected in human decidual, placental, and
      chorionic villous tissues and in a choriocarcinoma cell line BeWo. By in situ
      hybridization, vav mRNA was found to be expressed in the cytotrophoblast shell
      and columns and in the extravillous trophoblasts in the maternal decidua from the
      first through third trimesters. Vav mRNA was also detected in villous
      syncytiotrophoblasts during the second and third, but not the first, trimesters.
      When 1 microM oligodeoxynucleotide antisense to the vav mRNA was added to the
      medium, growth of BeWo cells was significantly inhibited. These results suggest
      that vav plays an important role for successful implantation and placental
      development by regulating development of trophoblasts.

PMID- 8547480
TI  - Concentrations of tumor necrosis factor alpha and progesterone within the bovine
      corpus luteum sampled by continuous-flow microdialysis during luteolysis in vivo.
AB  - Corpora lutea (CL) of mature, nonlactating Holstein cows (n = 12) each received
      surgical implants of a microdialysis system between Days 12 and 16 of an estrous
      cycle (estrus = Day 0). Fractions from dialyzed CL were collected every 30 min
      for 12 h each day for 7-9 days after surgery. Concurrent sampling of jugular
      venous blood allowed comparison between luteal dialysate and peripheral serum
      hormone concentrations. Six cows received no treatment, while 4 cows received
      prostaglandin F2 alpha (PGF; 25 mg, i.m.) and 2 cows received hCG (5000 IU, i.m.)
      within 48 h after surgery. Serum progesterone (P4) declined to < 1 ng/ml by Day
      20 +/- 0.5 in 4 of 6 nontreated cows and by Day 15 +/- 0.6 in all 4 PGF-treated
      cows. Both of the hCG-treated cows had increased serum and dialysate P4 after
      treatment and did not show evidence of luteolysis by the end of their sampling
      period (Days 22 and 18), and 2 of 6 nontreated cows did not show evidence of
      luteolysis by the end of their sampling period (Days 22 and 24). All 8 cows
      undergoing spontaneous or induced luteolysis showed a significant rise (p < 0.01)
      in dialysate (but not serum) tumor necrosis factor alpha (TNF) after P4 began to
      decline. From the start of the decline in dialysate P4, intervals to first
      detectable TNF and to peak TNF, and duration of TNF in the dialysate were 25.8 +/
      8 h, 38.3 +/- 8 h, and 42.3 +/- 7 h, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8547481
TI  - Development of normal mice from oocytes injected with secondary spermatocyte
      nuclei.
AB  - This study shows that the nucleus of the secondary spermatocyte can participate
      in syngamy and normal embryonic development. Spermatogenic cells were released
      from the seminiferous tubules of adult mice, and the secondary spermatocytes were
      selected according to the size of the whole cell and nucleus. The accuracy of
      this selection, evaluated by chromosome analysis, was 86%. Nuclei of presumptive
      secondary spermatocytes were freed from the cytoplasm and then injected
      individually into mature oocytes. This process itself did not activate the
      oocytes. The oocytes were electroactivated about 2 h after injection, at which
      time prematurely condensed chromosomes of the spermatocyte had become associated
      with the microtubules of a spindle. Following activation, the chromosomes of both
      the oocyte and spermatocyte completed their second meiotic division, culminating
      in the extrusion of two separate polar bodies and the formation of one male and
      one female pronucleus in about 75% of the oocytes into which spermatocyte nuclei
      had been injected. Two- or four-cell embryos arising from such oocytes were
      randomly selected and transplanted to foster mothers. Twenty-four percent
      developed into normal fertile offspring. The young born later to these offspring
      were all normal. The results of this study indicate that gametic imprinting of
      mouse spermatogenic cells is completed either in the testis before the second
      meiotic division or within the cytoplasm of a mature oocyte after artificial
      nuclear transfer.

PMID- 8547482
TI  - Ovarian and adrenal contributions to postnatal growth and differentiation of the
      rat uterus.
AB  - We tested the hypothesis that ovarian and/or adrenal factors contribute to
      uterine growth, differentiation, and acquisition of estrogen responsiveness in
      the postnatal rat. In untreated rats, normalized uterine weight (5.2 mg/10 g BW
      on postnatal days [PND] 1-10) increased by about 35% on PND 11-19; PND 6
      ovariectomy (OVX) eliminated this increase. Adrenalectomy (ADX) on PND 6 lowered
      normalized uterine weight only when combined with OVX and only on PND 16 and 19,
      demonstrating the presence of uterotropic adrenal products. OVX +/- ADX on PND 6
      delayed uterine gland genesis by about 2 days but did not alter final gland
      numbers. There was no change in the normal pattern of luminal epithelium
      morphology. A uterotropic response to 17 beta-estradiol (E2) occurred on PND 10
      in OVX rats and on PND 12 in OVX + ADX rats, but not until PND 14 in controls. We
      conclude that normal uterine growth is independent of the ovaries and adrenals
      prior to PND 10, partially dependent during PND 10-15, and completely dependent
      during PND 16-26. Additionally, a uterotropic response to exogenous E2 occurs
      concomitantly with, but independently of, the endogenous estrogen surge. Finally,
      while uterine gland genesis is slightly retarded by OVS +/- ADX, estrogens from
      these organs do not induce uterine differentiation.

PMID- 8547483
TI  - Complementary deoxyribonucleic acid cloning and characterization of mSP-10: the
      mouse homologue of human acrosomal protein SP-10.
AB  - Complementary DNA encoding the putative mouse homologue for human acrosomal
      protein SP-10, a candidate contraceptive vaccinogen, was cloned and sequenced.
      The entire open reading frame (amino acids 18 to 261) of the mouse SP-10 (mSP
      10), with the exception of the signal peptide (amino acids 1 to 17), was placed
      under the influence of inducible T7 RNA polymerase/promoter system to overproduce
      recombinant protein (re-mSP-10) in Escherichia coli. A six-histidine tag, which
      was coexpressed at the carboxyl terminus of re-mSP-10, provided the means for
      purification of re-mSP-10 by immobilized metal chelation affinity chromatography
      technique. The level of purity of re-mSP-10 thus obtained was determined by 2
      dimensional gel electrophoresis to be 98%. Immunoblotting with monoclonal and
      polyclonal antibodies previously generated against human or baboon SP-10 showed
      that mSP-10 shared significant antigenic similarity with its primate
      counterparts. The position of mSP-10 in the mouse genome was next mapped through
      segregation analysis of an interspecific backcross panel of 96 animals. Acrv1
      (assigned gene symbol for mSP-10) was localized in the proximal portion of mouse
      chromosome 9 in a region that exhibits synteny with human 11q23, the region to
      which ACRV1 (gene symbol for human SP-10) was previously mapped. These
      characterizations by combined immunological and gene mapping techniques
      established the cloned mSP-10 to be the mouse homologue of SP-10.

PMID- 8547484
TI  - Regulation of insulin-like growth factor-I and progesterone synthesis by insulin
      and growth hormone in the ovine ovary.
AB  - Insulin-like growth factor-I (IGF-I) is an intraovarian regulator of follicular
      development in the rat, but it is uncertain how applicable this model is to other
      species. Ovine granulosa and luteal cells were cultured for 2 wk in defined
      medium to investigate the regulation of ovarian IGF-I synthesis. IGF-I was
      measured by RIA of concentrated media extract, and progesterone production was
      also assessed. In granulosa cell cultures from preovulatory follicles, IGF-I
      output was initially undetectable with the output rising from about Day 6,
      whereas midcycle luteal cells produced low concentrations of IGF-I throughout the
      culture period. In granulosa cells, insulin in the range of 0.1-10 micrograms/ml
      stimulated a dose-dependent increase in output per day of IGF-I and also caused
      IGF-I production to start at an earlier time in culture, but a lower dosage (10
      ng/ml) consistently increased progesterone synthesis. High dosages of estradiol
      (10(-6) M) caused a small increase in IGF-I production whereas lower dosages had
      no effect. Growth hormone (GH) alone (10 ng/ml-10 micrograms/ml) did not
      stimulate either progesterone or IGF-I output. In the presence of insulin, GH
      caused a marked increase in progesterone but had no effect on IGF-I. These
      results suggest that IGF-I is not a major product of granulosa cells in the ewe,
      although there is low luteal production. Furthermore they indicate that the
      actions of the metabolic hormones insulin and GH on ovarian progesterone
      synthesis are probably mediated directly through their own receptors rather than
      through either ovarian IGF-I synthesis or the type 1 IGF receptor.

PMID- 8547485
TI  - Characterization of ovarian follicular cysts and associated endocrine profiles in
      dairy cows.
AB  - It is generally accepted that ovarian follicular cysts (cysts) are nonovulatory
      follicular structures that contribute to extended calving intervals.
      Follicle/cyst dynamics and the etiology of cysts are unclear. The present study
      was conducted to characterize follicle/cyst dynamics and to define endocrine
      changes (etiology) associated with cyst development. Thirty-two dairy cows were
      studied: controls (n = 6), cows with spontaneously occurring cysts (n = 14), and
      cows in which cysts were induced by exogenous steroid treatment (n = 12). Ovaries
      of cows were scanned daily by ultrasonography to record follicle/cyst dynamics.
      Blood was collected to determine endocrine changes associated with follicle/cyst
      life span. Three ovarian responses in cows with cysts were observed: persistence
      of cysts, turnover of cysts, or spontaneous recovery (self-recovered; turnover of
      cysts and replacement with a follicle that ovulated). Mean maximum size of cysts
      was larger (p < 0.05) than that of ovulatory follicles (2.80 +/- 0.19 vs. 1.60 +/
      0.05 cm). Mean interval from initial detection of follicle/cyst wave to
      detection of a new follicle/cyst wave in cows with cysts was longer (13.0 +/- 1.1
      days; p < 0.05) and more variable (6 to 26 days; p < 0.05) than in controls (8.5
      +/- 0.5 days and 6-14 days, respectively). Cysts grew at the same rate as
      follicles but continued to grow for an additional period of time. A transient
      increase in FSH preceded detection of all follicle/cyst waves.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8547486
TI  - Human intermediate trophoblasts express chorionic gonadotropin/luteinizing
      hormone receptor gene.
AB  - Human cyto- and synchtiotrophoblasts have recently been shown to contain
      functional hCG/LH receptors. The present study investigated whether human
      intermediate trophoblasts also contain these receptors. Six implantation sites
      from 4-8 wk of pregnancy were processed for in situ hybridization for hCG/LH
      receptors coupled with immunocytochemistry for human placental lactogen (hPL), an
      endocrine marker for intermediate trophoblasts. In addition, the sections were
      also double-immunostained for hCG/LH receptor and hPL proteins. The results
      showed that some but not all the intermediate trophoblasts contained hCG/LH
      receptors. The intermediate trophoblasts in endovascular locations contained more
      receptors than those in perivascular locations. Villus syncytiotrophoblasts
      contained the highest level of receptors, followed by intermediate trophoblasts
      in endovascular and perivascular locations and then villus cytotrophoblasts.
      These data, demonstrating the presence of hCG/LH receptors in intermediate
      trophoblasts, suggest a possible role for hCG in trophoblast invasion and
      maternal recognition of pregnancy.

PMID- 8547487
TI  - Monoclonal antiphosphatidylserine antibody inhibits intercellular fusion of the
      choriocarcinoma line, JAR.
AB  - Naturally occurring antiphospholipid antibodies are strongly associated with
      placental dysfunction and severe obstetrical complications. We have produced
      three monoclonal antiphospholipid antibodies that differentiate between
      phosphatidylserine (PS)- and cardiolipin (CL)-dependent antigens, 3SB9b (CL
      /PS+), BA3B5C4 (CL+/PS+), and D11A4 (CL+/PS-). We tested these monoclonal
      antiphospholipid antibodies in an assay for intertrophoblastic fusion. A JAR
      choriocarcinoma cell line was induced to undergo intercellular fusion by
      forskolin in the presence or absence of monoclonal antiphospholipid antibodies.
      The amount of syncytium formation was quantified by using fluorescein
      isothiocyanate (FITC)-conjugated anti-desmosome antibody to visualize
      intercellular membranes and propidium iodide to stain nuclei and by counting
      those cells with multiple nuclei. Without the presence of antiphospholipid
      antibodies, and in cultures containing BA3B5C4 (CL+/PS+) or D11A4 (CL+/PS-),
      approximately 70% of JAR formed syncytial cells after 24 h of forskolin
      treatment. Less than 13% of the cells formed synctia in 2-day cultures that were
      not exposed to forskolin or that contained forskolin in the presence of 3SB9b (CL
      /PS+). These data suggest that phosphatidylserine is externalized during
      intertrophoblastic fusion and that antiphospholipid antibody with reactivity
      against PS, but not CL, can affect placental development by interfering with the
      normal formation of syncytiotrophoblast.

PMID- 8547488
TI  - Expression of epidermal growth factor (EGF) and the EGF receptor in the porcine
      oviduct.
AB  - The production, secretion, and localization of epidermal growth factor (EGF) and
      the distribution of the EGF receptor (EGF-R) were examined in the isthmus (I) and
      ampulla (A) of the oviducts from cyclic (C) and early-pregnant (P) gilts.
      Sexually mature gilts (n = 20) were divided equally into two groups: C and P. P
      gilts were bred twice (at 0 and 24 h), and all gilts were killed 48 h after onset
      of estrus. After removal of reproductive tracts, oviducts were isolated, flushed,
      opened longitudinally, divided by anatomical region, cut into 1-3-mm3 pieces, and
      placed in Dulbecco's modified Eagle's Essential medium (DMEM: F-12 + ITS
      [insulin, 5 micrograms/ml; transferrin, 5 micrograms/ml; and selenious acid, 5
      ng/ml] + antibiotic). Half the tissue and medium were immediately homogenized and
      centrifuged, and the supernatant was removed. The remaining tissue was cultured
      in the medium for 24 h at 37 degrees C and 5% CO2, then prepared similarly for
      analysis. EGF was measured in the supernatant by a heterologous RIA.
      Concentration of EGF was expressed as nanogram/milliliter of EGF per milligram of
      protein in wet tissue. EGF concentrations were present in both regions of the
      oviducts of C and P gilts. It was greater in I than in A tissues for both C (I =
      16.21 ng/ml vs. A = 13.91 ng/ml; p < 0.05) and P gilts (I = 14.27 ng/ml vs. A =
      12.53 ng/ml; p < 0.10). Higher concentrations of EGF were found in I tissue of C
      gilts than in P gilts (C = 16.21 ng/ml vs. P = 14.27 ng/ml; p < 0.05). The media
      assayed from cultured explants of I and A sections from C and P gilts gave
      results that were highly correlated with those of immediately prepared tissue
      sections. Localization of EGF in frozen oviductal tissue sections was
      demonstrated by immunohistochemistry. The primary site of EGF immunostaining
      occurred in the epithelial cells (with highest intensity at the apical border) of
      both C and P gilts. A and I tissue sections from C gilts showed localization of
      EGF immunostaining mainly in epithelial cells and lamina propria cells, while
      those from P gilts stained less intensely. The presence of EGF-R was shown by
      incubating tissue imprints and frozen sections with EGF-erythrosin
      isothiocyanate, which revealed that EGF-R were distributed mainly on the
      membranes of epithelial cells. The study indicates that EGF and EGF-R are present
      in oviductal epithelial cells in both C and P gilts, with the highest
      concentration of EGF in C gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547489
TI  - Expression and selective cellular localization of granulocyte-macrophage colony
      stimulating factor (GM-CSF) and GM-CSF alpha and beta receptor messenger
      ribonucleic acid and protein in human ovarian tissue.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization,
      and immunohistochemical observations revealed that human ovarian tissue expressed
      granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as GM-CSF alpha
      and beta receptor (R) mRNA and protein. The RT-PCR products revealed the
      predicted 286-, 546-, and 380-bp fragments for GM-CSF, GM-CSF alpha R, and GM-CSF
      beta R, respectively, which were further verified by restriction enzyme digestion
      analysis. In situ hybridization revealed that the theca interna of the large
      follicles and luteal cells are the exclusive site of GM-CSF mRNA expression.
      Furthermore, immunohistochemical studies using specific monoclonal antibodies
      indicated that the theca interna of the large follicles are the exclusive site of
      GM-CSF protein, whereas theca externa and to a lesser extent the granulosa cells
      are the major sites of GM-CSF alpha R and beta R proteins. Atretic follicles and
      follicular cysts showed very low or no detectable levels of GM-CSF and GM-CSF
      alpha R and beta R. In the luteal tissue, both the small and large luteal cells
      of early luteal (Days 14-19) and midluteal (Days 20-25) phase expressed GM-CSF
      mRNA and protein as well as GM-CSF alpha R and beta R proteins, and their
      immunostaining intensity was similar to that seen with theca cells. Luteal cells
      from late luteal phase (Days 26-28), corpus albicans, and ectopic pregnancy
      expressed a low level of GM-CSF, GM-CSF alpha R, and GM-CSF beta R mRNA and
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547490
TI  - Immunoneutralization of inhibin and estradiol during the follicular phase of the
      estrous cycle in cows.
AB  - To investigate the physiological importance of inhibin and estradiol in the
      regulation of FSH secretion during the follicular phase of the estrous-cycle in
      cows, animals were passively immunized against the two hormones. Sixteen cows
      were divided into four equal groups and given injections of prostaglandin F2
      alpha (PG) i.m. twice at 8-h intervals on Day 10 of the estrous cycle (Day 0 =
      day of estrus) to induce luteal regression. At 48 h after the first PG injection,
      each group of four cows received injections of one of the following: 100 ml
      castrated goat serum (control serum), 100 ml antiserum against inhibin, 100 ml
      antiserum against estradiol, or a combination of 100 ml inhibin antiserum and 100
      ml estradiol antiserum. The LH surge occurred within 2 days after injection of
      the control serum or inhibin antiserum, whereas it was not detected in either of
      the groups passively immunized against estradiol, indicating that passive
      immunization against estradiol blocks a positive feedback effect of estradiol on
      LH secretion. There was no clear difference in basal concentrations of LH among
      the four groups. Injection of the inhibin antiserum resulted in a marked increase
      (p < 0.01) in plasma concentrations of FSH compared with values in the control
      group, while there were no significant changes in concentrations of plasma FSH
      after injection of the estradiol antiserum. Combined administration of the
      inhibin and estradiol antisera also produced a marked increase (p < 0.01) in
      plasma concentrations of FSH. The FSH response to the combined immunization was
      longer in duration than the FSH response to immunization with inhibin
      alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547491
TI  - Pubertal development of male African catfish (Clarias gariepinus). Pituitary
      ultrastructure and responsiveness to gonadotropin-releasing hormone.
AB  - Pubertal development was studied in male African catfish by immunocytochemical
      examination of pituitary gonadotrophs and by monitoring the responsiveness of
      gonadotropin (GTH) secretion to salmon GnRH analogue (sGnRHa) in vitro.
      Experiments were carried out with fish from 9 to 28 wk of age. Fish were assigned
      to four groups, according to the stage of spermatogenesis: I, spermatogonia
      alone; II, spermatogonia and spermatocytes; III, spermatogonia, spermatocytes,
      and spermatids; IV, all germ cell stages, including spermatozoa. Basal and sGnRHa
      stimulated secretion of the LH-like GTH II increased 3- to 4-fold from stage I to
      II and from stage II to III, whereas a 15-fold increase was recorded from stage
      III to IV. The ED50 values of sGnRHa varied between 0.08 and 0.49 nM, stages II
      and III being less sensitive. The highest dosage of sGnRHa (100 nM) led to a
      reduction of GTH secretion. In the first three stages, the pituitary secreted
      large amounts of free alpha-subunit while free GTH II beta-subunit was not
      detected at any stage of development. Antisera against GTH II and its alpha- and
      beta-subunits were used for immunocytochemical studies. In stages I and II, two
      subtypes of gonadotrophs, which differed in the size and labeling intensity of
      their secretory granules, were present. Both types of granules were
      immunopositive for the two subunits of GTH II. In stages III and IV, only
      gonadotrophs of the subtype with the larger granules were found. Globules and
      irregular, membrane-bound masses (IMs), probably arising through fusion of
      secretory granules, appeared in the gonadotrophs in stage III and became more
      prominent in stage IV. Globules and IMs were immunopositive for the beta-subunit
      but negative for the alpha-subunit. We conclude that the two subtypes of
      gonadotrophs represent different developmental stages of GTH II-producing cells,
      as they shared immunolabeling for the alpha- and the beta-subunits of GTH II. The
      scarcity of GTH II beta-subunit may be rate-limiting for the amount of intact GTH
      II available for secretion, particularly at early stages of development. In
      contrast, at more advanced stages when the readily releasable pool of GTH II has
      greatly increased, the amount of GTH II also appears to be controlled by
      modification or elimination of the alpha-subunit from globules and IMs.

PMID- 8547492
TI  - Expression of follicle-stimulating hormone and luteinizing hormone receptor
      messenger ribonucleic acids in bovine follicles during the first follicular wave.
AB  - The objective of the present study was to characterize expression of mRNAs
      encoding FSH and LH receptors during follicular development and at different
      stages of the first follicular wave in cattle. Following estrus, groups of
      heifers (3-5 per group) were ovariectomized on the day of initiation of the first
      follicular wave (as determined by ultrasonography; Day 0), or on Days 2, 4, 6, 8,
      or 10 after initiation of the first wave. FSH and LH receptor mRNAs were detected
      within follicles > or = 4 mm and in some smaller follicles by in situ
      hybridization and were quantified by image analysis. FSH receptor mRNA was
      expressed in granulosa cells of all growing follicles, starting in some follicles
      with only one layer of granulosa cells. Irrespective of day of the follicular
      wave, the level of expression of FSH receptor mRNA in granulosa cells of healthy
      antral follicles ranging from 0.5 to 14 mm in diameter did not vary significantly
      with follicular size (r = 0.02, p > 0.10). Expression of LH receptor mRNA was
      first observed in theca interna cells of follicles shortly after antral
      formation. Irrespective of day of the follicular wave, the levels of LH receptor
      mRNA in theca interna cells of healthy antral follicles ranging from 0.5 to 14 mm
      increased with follicular size (r = 0.39, p < 0.01). In granulosa cells, LH
      receptor mRNA was expressed only in healthy follicles > 9 mm in diameter and was
      first observed in the dominant follicles collected on Day 4. Expression of mRNA
      for LH receptor, but not for FSH receptor, changed (p < 0.01) with the stage of
      the first follicular wave.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547493
TI  - Changes in protein prenylation and prenyltransferase activity in the rat
      seminiferous epithelium during early stages of spermatogenesis.
AB  - Changes in protein prenyltransferase activity, levels of prenylated protein, and
      the type of isoprenoid modification was described in cells of rat seminifereous
      epithelium and correlated with differentiative events of spermatogenesis. The
      activity of protein farnesyltransferase (PFT) was at least 10-fold higher than
      that for protein geranylgeranyltransferase-I (PGGT-I) in seminiferous epithelium
      and spermatogenic cells of prepubertal rats of different ages. Both activities
      increased during the meiotic stages of differentiation and peaked at 23 days of
      age. The activity of farnesyltransferase in seminiferous epithelium was the same
      as that in mixed spermatogenic cell populations from animals aged 9 and 23 days,
      indicating that the activity of this enzyme in somatic cells and germ cells was
      similar at these ages. Farnesyltransferase activities were similar and low in
      both pachytene spermatocytes and round spermatids from adult rats; however, the
      activity in pachytene spermatocytes from 23-day old animals was 2-fold higher
      than in adults. The highest activity was associated with intermediate-sized
      spermatocytes appearing late during meiosis. PGGT-I activity was at least 10-fold
      lower than farnesyltransferase activity and was not significantly different among
      all cell populations. Differentiation-dependent in vivo protein prenylation was
      demonstrated by labeling of seminiferous epithelium with [3H]mevalonic acid at
      different prepubertal ages. Total protein prenylation and the ratio of
      geranylgeranylated to farnesylated protein, in contrast to prenyltransferase
      activity, decreased with increasing age. Although 20-30-kDa proteins were the
      most highly labeled at all ages, [3H]-proteins from different-aged prepubertal
      rats showed age-dependent changes in the level of prenylation of at least 14
      proteins as determined by two-dimensional (2D) electrophoresis. Prenylated
      proteins of round spermatids were distinguished from those of the spermatocytes
      by the lack of many 20-30-kDa proteins and by low geranylgeranyl/farnesyl (GG/F)
      ratios. These results show that independent changes in prenyltransferase activity
      and protein prenylation accompany the differentiation events during the
      premeiotic and meiotic stages of spermatogenesis. This suggests that prenylation
      in the seminiferous epithelium may be more dependent on available protein
      substrate than on protein prenyltransferase activity.

PMID- 8547495
TI  - USPHS/IDSA guidelines for the prevention of opportunistic infections in persons
      infected with human immunodeficiency virus: introduction. USPHS/IDSA Prevention
      of Opportunistic Infections Working Group.

PMID- 8547494
TI  - Stage-specific expression of cytokine and receptor messenger ribonucleic acids in
      human preimplantation embryos.
AB  - There is considerable evidence to suggest that polypeptide growth factors from
      either the oviduct or the endometrium can control preimplantation development of
      the mammalian embryo. These act directly through receptors expressed on the
      embryo. In addition, embryos also produce growth factors. The reverse
      transcriptase-polymerase chain reaction (RT-PCR) was used to determine the
      pattern of expression of mRNAs encoding several growth factor ligand and receptor
      genes throughout preimplantation development of cryopreserved human embryos.
      Transcripts encoding the receptor for c-fms, the receptor for colony-stimulating
      factor-1 (CSF-1), and c-kit (the receptor for stem cell factor [SCF]) were
      expressed throughout preimplantation development. Other growth factor ligand and
      receptor transcripts were expressed in a stage-specific manner: these included
      receptors for interleukin (IL)-6 (IL-6R), leukemia inhibitory factor (LIFR),
      tumor necrosis factor alpha (TNF alpha) (TNFRp80 and TNFRp60), and gp130. The
      transcripts for gp130 and the ligand SCF showed stage-specific splice variants.
      Blastocysts expressed a novel cDNA encoding gp130, which predicts a truncated
      form lacking the intracellular signaling domain. No expression of mRNAs encoding
      LIF, CSF-1, or the cloned receptor for platelet-activating factor was seen in any
      embryonic stage studied. We have shown that RT-PCR provides a sensitive and
      powerful method for identifying transcripts encoding growth factors and their
      receptors in single human embryos. The method is economical, allowing the
      expression pattern of many genes to be determined from a single embryo. These
      data are important in defining which cytokines may be involved in regulating
      human preimplantation development and when they may act.

PMID- 8547496
TI  - Prospects for preventing cryptococcosis in persons infected with human
      immunodeficiency virus.
AB  - Cryptococcosis is a major cause of illness and death among persons infected with
      human immunodeficiency virus (HIV). Its management must include both initial and
      maintenance treatment. Although most authorities favor an initial period of
      therapy with amphotericin B for acute cryptococcosis, the triazoles play a role
      in both the management of acute disease and subsequent maintenance therapy. AIDS
      surveillance data collected by the Centers for Disease Control and Prevention
      document the occurrence of cryptococcosis in more than 17,000 (6.2%) of adults
      with AIDS in the United States, although this figure is known to be an
      underestimate. The risk of cryptococcosis among HIV-infected persons is highest
      at CD4+ lymphocyte counts of < 100/microL. Although cryptococcosis is especially
      frequent among AIDS patients who are black, male, or injection drug users, the
      explanations for these patterns remain unclear. Whether geographic differences in
      rates of cryptococcosis result from variations in the environmental distribution
      of Cryptococcus neoformans as well as in the distribution of HIV infection is
      also unclear. Although exposure to pigeon feces is the best known of the putative
      exposure-related risk factors, proof is lacking that avian excreta are the
      primary environmental source of the organism in most cases of cryptococcosis.
      Prophylaxis with triazoles can prevent cryptococcosis and may be considered for
      adults and adolescents with CD4+ counts of < 50/microL. However, it is uncertain
      whether prophylaxis will affect survival, be cost-effective, or have an adverse
      impact on the susceptibility of a variety of fungi to antifungal drugs. Vaccines
      and monoclonal antibodies designed to prevent or modify cryptococcosis in HIV
      infected persons are in the experimental stage.

PMID- 8547497
TI  - Disseminated histoplasmosis in persons infected with human immunodeficiency
      virus.
AB  - Disseminated histoplasmosis is an AIDS-defining illness that occurs in about 5%
      of AIDS patients residing in histoplasmosis-endemic areas of the United States
      (the Mississippi and Ohio river valleys). This disease develops as a result of
      acute infection and perhaps also as the result of reactivation of latent
      infection: cases reported from areas such as New York City, where histoplasmosis
      is not endemic, are most likely due to reactivation of an infection acquired
      earlier in a histoplasmosis-endemic area, while cases in histoplasmosis-endemic
      areas are most likely due to acute infection, especially in outbreak settings.
      Disseminated histoplasmosis in HIV-infected patients is usually associated with
      advanced immunosuppression, with CD4+ lymphocyte counts of < 75/mm3. Currently,
      histoplasmin skin testing of HIV-infected patients does not seem to be useful in
      detecting previous exposure and therefore is not helpful in identifying groups of
      patients who are at risk for dissemination and who should be targeted for
      preventive efforts. The current public health recommendation for HIV-infected
      patients is to avoid exposure to sites likely to harbor high levels of
      Histoplasma capsulatum, such as chicken coops and bird roosts. The role of
      chemoprophylaxis is not clear, but an ongoing study by the Mycoses Study Group is
      evaluating the role of prophylactic itraconazole. If strategies for the
      prevention of disseminated histoplasmosis in HIV-infected patients are to be
      improved, studies must better define the risk factors for this opportunistic
      infection, describe its natural history, and develop more reliable tests to
      predict its development.

PMID- 8547498
TI  - Opportunistic coccidioidomycosis in patients infected with human immunodeficiency
      virus: prevention issues and priorities.
AB  - Coccidioidomycosis is an uncommon AIDS-defining illness that is endemic in the
      southwestern United States. In profoundly immunodeficient patients infected with
      human immunodeficiency virus (HIV), the disease is usually manifest as severe
      pulmonary infection and is associated with high mortality. Although diagnosis is
      often made by routine serological tests, these appear to be less sensitive than
      when used for patients who are not HIV-infected. New ways to diagnose the
      infection in HIV-infected patients earlier and with more certainty are urgently
      needed. The optimal antifungal regimen for active disease in HIV-infected
      patients is currently undefined, but following acute disease in severely
      immunocompromised HIV-infected patients (CD4 lymphocyte count, < 200/microL),
      lifelong systemic antifungal therapy is recommended. The role of chemoprophylaxis
      for HIV-infected patients in the area of endemic disease is also unclear.
      Improvement of preventive strategies must await the results of well-designed
      future studies to determine risk factors, particularly environmental factors, for
      development of coccidioidomycosis and to determine the proportion of disease due
      to new vs. reactivated infection. These studies are also needed to elucidate the
      role and efficacy of different types of antifungal drug therapies and the
      specific dosages useful for prevention, treatment, and long-term control of these
      infections.

PMID- 8547499
TI  - Herpesvirus infections in persons infected with human immunodeficiency virus.
AB  - Herpesviruses are among the most common causes of infections of humans. Viruses
      in this family share the unique biological property of being able to establish
      latency and to recur. Furthermore, chronic excretion of virus is not uncommon. In
      the immunocompromised host, including persons with human immunodeficiency virus
      (HIV) infection, herpesvirus disease can be particularly severe, resulting in
      chronic, persistent, active infection and, in some cases, life-threatening
      disease. The most pathogenic of the herpesviruses in patients with AIDS include
      herpes simplex viruses, human cytomegalovirus, and varicella-zoster virus.
      Disease caused by Epstein-Barr virus, particularly opportunistic malignancies,
      has been recognized. A new herpesvirus that is associated with Kaposi's sarcoma
      was recently described. On the other hand, disease caused by human herpesviruses
      6 and 7 in persons infected with HIV remains to be unequivocally recognized.
      Prevention of exposure to herpesviruses, disease, and recurrence requires
      different measures than those for some of the other opportunistic infections in
      HIV-infected patients; this is because herpesvirus disease develops in most of
      these individuals as a result of reactivation rather than primary infection.
      Thus, approaches to the prevention and control of herpesvirus infections must be
      individualized according to both the type of virus as well as the type of
      infection (i.e., primary or recurrent). We discuss recommended measures for the
      prevention and control of these infections.

PMID- 8547500
TI  - USPHS/IDSA guidelines for the prevention of opportunistic infections in persons
      infected with human immunodeficiency virus: an overview. USPHS/IDSA Prevention of
      Opportunistic Infections Working Group.

PMID- 8547501
TI  - Human papillomavirus infection and associated disease in persons infected with
      human immunodeficiency virus.
AB  - Genital infection with human papillomavirus (HPV) is the most common sexually
      transmitted infection in the United States. Genital or anal infection with
      oncogenic types of HPV, particularly types 16 and 18, can cause precancerous
      lesions of the squamous epithelium. Infection with human immunodeficiency virus
      (HIV) increases the risk for HPV-associated genital neoplasias in both women and
      men. Detectable cervical and anal HPV infection is more prevalent among women and
      men with HIV infection than among those who are HIV-seronegative, and the
      magnitude of the increase in prevalence is proportionate to the severity of
      immunosuppression. Coinfection with HIV and HPV increases the risk for genital
      intraepithelial neoplasia, and the increase in this risk also reflects the
      severity of immunosuppression. One difficulty complicating elucidation of the
      association between HIV and HPV infections is that the risk factors for
      acquisition and transmission of the two viruses are similar. The strength of this
      association represents a burgeoning health problem, yet there are no treatment
      guidelines aimed specifically at HIV-infected individuals with HPV-associated
      genital neoplasias. Treatment of HPV-associated cervical disease in HIV-infected
      women may be further complicated by a greater risk of treatment failure and
      recurrence than exists among HIV-seronegative women; it is not known whether
      dysplasia progresses to invasive disease more rapidly in women infected with HIV.
      A thorough understanding of the associations among HIV, HPV, and HPV-associated
      disease is essential to the development of effective strategies for intervention
      and prevention.

PMID- 8547502
TI  - Quality standards for preventing opportunistic infections related to human
      immunodeficiency virus and their implementation.

PMID- 8547503
TI  - Quality standard for the enumeration of CD4+ lymphocytes in adults and
      adolescents infected with human immunodeficiency virus.

PMID- 8547504
TI  - Quality standard for the prophylaxis of Pneumocystis carinii pneumonia in adults
      and adolescents infected with human immunodeficiency virus.

PMID- 8547505
TI  - Quality standard for the identification and treatment of persons coinfected with
      human immunodeficiency virus and Mycobacterium tuberculosis.

PMID- 8547506
TI  - Quality standard for the prophylaxis of Pneumocystis carinii pneumonia in infants
      and children born to women infected with human immunodeficiency virus.

PMID- 8547507
TI  - Quality standard for the enumeration of CD4+ lymphocytes in infants and children
      exposed to or infected with human immunodeficiency virus.

PMID- 8547508
TI  - Quality standard for the immunization of infants and children born to women
      infected with human immunodeficiency virus.

PMID- 8547509
TI  - Indicators for assessment of compliance with quality standards for the prevention
      of opportunistic infections in persons infected with human immunodeficiency
      virus.

PMID- 8547510
TI  - USPHS/IDSA guidelines for the prevention of opportunistic infections in persons
      infected with human immunodeficiency virus: disease-specific recommendations.
      USPHS/IDSA Prevention of Opportunistic Infections Working Group.

PMID- 8547511
TI  - Preventing Pneumocystis carinii pneumonia in persons infected with human
      immunodeficiency virus.
AB  - Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults
      infected with human immunodeficiency virus (HIV) has declined, no decline in PCP
      incidence has been observed among HIV-infected children, and PCP remains the most
      common serious opportunistic infection among both adults and children in the
      United States. Some evidence of airborne transmission of P. carinii exists, and
      some clusters of cases of PCP have been reported; however, data are insufficient
      to recommend that persons with PCP be separated from immunosuppressed persons as
      a standard practice. The incidence of PCP can be reduced substantially if persons
      at risk for PCP are identified and receive adequate chemoprophylaxis. Several
      drugs and drug combinations are highly effective in preventing PCP. For both
      adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the
      preferred form of prophylaxis. Adverse effects are commonly associated with the
      use of TMP-SMZ and in some cases may necessitate withdrawal of the drug until the
      effects resolve. However, reintroduction at the same dose or at a lower and
      gradually increasing dose will often permit the continued use of TMP-SMZ. For
      persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are
      effective alternatives. A third alternative is aerosolized pentamidine.
      Additional drugs of unproven efficacy but of potential use in exceptional cases
      are available.

PMID- 8547512
TI  - Preventing toxoplasmic encephalitis in persons infected with human
      immunodeficiency virus.
AB  - Toxoplasmic encephalitis (TE) is the second most common AIDS-related
      opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS
      who are seropositive for antibodies to Toxoplasma gondii and have CD4+ T
      lymphocyte counts of < 100/mm3. Primary toxoplasmic infection usually is acquired
      by ingestion of T. gondii oocysts from soil contaminated by cat feces or by
      ingestion of tissue cysts present in undercooked red meats. In patients with
      AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that
      remained latent after the primary infection. Detection of IgG antibodies to
      Toxoplasma indicates prior infection and the possible presence of tissue cysts
      and, thus, risk for developing TE. A regimen of trimethoprim-sulfamethoxazole or
      dapsone plus pyrimethamine with leucovorin is recommended for persons infected
      with the human immunodeficiency virus (HIV) and who are seropositive for IgG to
      Toxoplasma after their CD4+ T lymphocyte counts fall to < 100/mm3. HIV-infected
      persons who are seronegative for IgG to Toxoplasma should be counseled to protect
      themselves from primary toxoplasmic infection by eating only well-cooked meats
      and washing their hands after outdoor activities involving soil contact; if they
      have a cat, they should feed it only commercial or well-cooked foods, keep it
      indoors, and make sure that the litter box is changed daily. HIV-infected persons
      who are Toxoplasma seropositive may also be advised about these preventive
      behavioral practices.

PMID- 8547513
TI  - Cryptosporidiosis: sources of infection and guidelines for prevention.
AB  - Cryptosporidium parvum is an important emerging pathogen in the United States and
      a cause of severe, life-threatening disease in patients with AIDS. No safe and
      effective form of specific treatment for cryptosporidiosis has been identified to
      date. The parasite is transmitted by ingestion of oocysts excreted in the feces
      of infected humans or animals. The infection can therefore be transmitted from
      person to person through ingestion of contaminated water (drinking water and
      water used for recreational purposes) or food, from animal to person, or by
      contact with fecally contaminated environmental surfaces. Outbreaks associated
      with all of these modes of transmission have been documented. Patients with human
      immunodeficiency virus infection should be made more aware of the many ways that
      Cryptosporidium species are transmitted, and they should be given guidance on how
      to reduce the risk of exposure. This article summarizes existing data on the
      various modes of transmission. It includes an in-depth look at waterborne
      transmission because as more research data are made available to the public,
      physicians will increasingly be asked by patients about the importance of this
      source of infection compared with other sources of infection.

PMID- 8547514
TI  - Microsporidiosis as an AIDS-related opportunistic infection.
AB  - The clinical manifestations of AIDS-related microsporidiosis range from mild or
      asymptomatic infections to debilitating illness involving the gastrointestinal,
      respiratory, or urogenital tracts or the eyes. Intestinobiliary infections with
      Enterocytozoon bieneusi are the most common microsporidial diseases, but
      disseminated infections with Encephalitozoon hellem, Encephalitozoon cuniculi,
      and Septata intestinalis are being increasingly recognized. The isolation of
      infective microsporidial spores from urine and respiratory secretions and the
      presence of spores in stool and duodenal aspirates suggest that person-to-person
      transmission may occur. Primary infection may also occur by inhalation or
      ingestion of spores from environmental sources or by zoonotic transmission.
      Development of guidelines for prevention of microsporidiosis will require that
      sources of infection and modes of transmission be more clearly elucidated. The
      presence of infective spores in bodily fluids, however, suggests that precautions
      when handling body fluids in clinical settings and personal hygiene measures such
      as hand washing may help to prevent primary infections.

PMID- 8547515
TI  - Tuberculosis as an opportunistic disease in persons infected with human
      immunodeficiency virus.
AB  - Tuberculosis, a bacterial disease caused by the Mycobacterium tuberculosis
      complex, is becoming an increasingly common opportunistic disease in persons
      infected with the human immunodeficiency virus (HIV). M. tuberculosis is
      transmitted from person-to-person by airborne droplet nuclei. Persons who are
      exposed to these droplet nuclei in poorly ventilated environments are at risk of
      becoming infected with M. tuberculosis. HIV infection is probably the most
      significant risk factor associated with progression from latent M. tuberculosis
      infection to active disease. Thus, HIV-infected persons should avoid exposure to
      M. tuberculosis, they should be screened for evidence of latent infection with
      the tuberculin skin test, and they should be offered preventive therapy. Because
      many severely immunosuppressed anergic HIV-infected persons have been found to
      have an increased risk of developing active tuberculosis, decisions to use
      preventive therapy should be individualized on the basis of the local prevalence
      of tuberculosis and drug-resistance patterns. Persons with active tuberculosis
      should receive at least 6 months of treatment with recommended regimens,
      preferably with directly observed therapy, to ensure adequate bacteriologic
      response, completion of therapy, and cure. Chronic suppressive therapy after
      completion of therapy is currently not recommended.

PMID- 8547516
TI  - Preventing disseminated Mycobacterium avium complex disease in patients infected
      with human immunodeficiency virus.
AB  - Disseminated Mycobacterium avium complex (MAC) infection is an important late
      stage complication of infection with the human immunodeficiency virus. Since MAC
      is widely dispersed in the environment, the source of infection for patients with
      disseminated MAC generally cannot be determined. Therefore, specific
      recommendations for avoiding exposure are not supported at this time. Routine
      screening of stools and sputum to detect MAC colonization as a means of targeting
      prophylaxis for disseminated disease is also not recommended at present. Two
      randomized, placebo-controlled trials have demonstrated that prophylactic use of
      rifabutin in persons with low CD4 lymphocyte counts results in a 50% decrease in
      MAC bacteremia as well as a reduction in some signs, symptoms, and laboratory
      abnormalities associated with MAC disease. Thus a prophylactic daily dose of
      rifabutin (300 mg) should be considered for adults who have had a previous AIDS
      defining opportunistic illness and who have a CD4 lymphocyte count of <
      75/microL. Many experts would consider prophylaxis appropriate only when the CD4
      lymphocyte count is < 50/microL, particularly when there has not been a previous
      AIDS-defining opportunistic infection. Clinicians should be aware of drug
      interactions and potential adverse effects associated with the use of rifabutin.
      Preliminary reports of randomized, placebo-controlled trials suggest that
      chemoprophylaxis with clarithromycin is also effective in the prevention of
      disseminated MAC disease, and evaluation of other agents is under way.
      Prophylaxis for disseminated MAC infection in children has not been evaluated but
      is presumed to be as effective as that in adults. Decisions regarding initiation
      of MAC chemoprophylaxis should be individualized.

PMID- 8547517
TI  - Preventing bacterial respiratory tract infections among persons infected with
      human immunodeficiency virus.
AB  - Bacterial respiratory tract infections occur frequently in persons infected with
      human immunodeficiency virus (HIV) and may be caused by a wide variety of
      pathogens. Pneumonia is the most commonly diagnosed respiratory infection in HIV
      infected persons and is more common in those persons than in non-HIV-infected
      ones. HIV-infected persons have a much higher risk of pneumococcal disease than
      do noninfected controls, and disease may occur relatively early in the course of
      HIV infection. While mortality associated with the disease does not seem to be
      high among HIV-infected persons, there is a higher rate of recurrence of the
      disease in that population. Risk factors for pneumococcal disease in HIV-infected
      persons are not well characterized. Though efficacy data are limited, the 23
      valent polysaccharide pneumococcal vaccine is recommended for use early in the
      course of HIV infection. There are no data suggesting that HIV-infected persons
      should be revaccinated routinely. Antiretroviral agents may enhance the
      immunologic response to the polysaccharide vaccine. Prophylactic antibiotics may
      have a role in preventing recurrences of severe bacterial respiratory infections,
      and intravenous immunoglobulin may be useful in preventing serious bacterial
      infections in HIV-infected children. HIV-infected persons are also at greater
      risk for serious infections with Haemophilus influenzae than are non-HIV-infected
      persons. Vaccination against H. influenzae type b (Hib) is recommended for HIV
      infected children but not for adults. Antimicrobial drug-resistant strains of
      Streptococcus pneumoniae and H. influenzae have become more prevalent recently
      and consequently have impacted on strategies for prevention and treatment of
      those infections.

PMID- 8547518
TI  - Bacterial enteric infections in persons infected with human immunodeficiency
      virus.
AB  - We review the epidemiology and prevention of and future research priorities for
      bacterial enteric infections in persons infected with the human immunodeficiency
      virus (HIV). HIV-infected persons are more frequently infected with Salmonella,
      Campylobacter, Listeria, and (possibly) Shigella species than are individuals not
      infected with HIV. In addition, Salmonella and (possibly) Campylobacter
      infections are more likely to be severe, recurrent, or persistent and associated
      with extraintestinal disease when they occur in HIV-infected persons. Infections
      caused by Shigella and Vibrio species can also result in more serious disease in
      HIV-infected persons than in those not infected with HIV. Risk of these
      infections can be reduced with proper precautions, particularly those pertaining
      to food hygiene, animal contact, and travel. Individuals infected with HIV should
      be informed of their increased risk of acquiring these diseases and should be
      counseled on the recommended precautions.

PMID- 8547519
TI  - Infections associated with Bartonella species in persons infected with human
      immunodeficiency virus.
AB  - Two members of the genus Bartonella, Bartonella quintana (formerly Rochalimaea
      quintana) and Bartonella henselae (formerly Rochalimaea henselae), have recently
      been recognized as agents of severe or fatal disease in patients infected with
      human immunodeficiency virus (HIV). The development of infection with B. henselae
      in HIV-infected individuals has been associated with traumatic contact with cats
      (scratches or bites), and domestic cats have been identified as a major reservoir
      for this organism. Specific information regarding the transmission of B. henselae
      to humans is not yet available, but common-sense precautions that minimize
      exposure to cat-associated organisms are appropriate. Preliminary accounts
      suggest that B. quintana infections are more common than B. henselae infections
      among HIV-infected individuals in San Francisco. The source of infection with B.
      quintana and the mechanism of its transmission remain unknown.

PMID- 8547520
TI  - Opportunistic candidal infections in patients infected with human
      immunodeficiency virus: prevention issues and priorities.
AB  - Mucosal candidiasis (oropharyngeal, esophageal, and vulvovaginal candidiasis) has
      been among the most prominent opportunistic infections in persons infected with
      human immunodeficiency virus (HIV). Esophageal candidiasis, an AIDS-defining
      illness, accounted for 15% of the AIDS-defining illnesses in adults and
      adolescents diagnosed in the United States through 1992. The diagnosis of
      oropharyngeal and vaginal candidiasis is based on clinically consistent signs and
      symptoms and a positive culture or a positive gram, KOH, or calcofluor stain,
      whereas the diagnosis of esophageal and pulmonary candidiasis is based on
      histopathology. Although a prospective controlled trial showed that prophylaxis
      with fluconazole can reduce the risk of mucosal candidiasis in patients with
      advanced HIV disease, routine primary prophylaxis is not recommended because of
      the effectiveness of therapy for acute disease, the low mortality associated with
      mucosal candidiasis, the potential for development of drug-resistant candidal
      infection, and the cost of prophylaxis. The probability of recurrences increases
      as CD4 counts decline. Nonetheless, many experts do not recommend chronic
      prophylaxis to prevent recurrent oropharyngeal and vulvovaginal candidiasis, for
      the same reasons that primary prophylaxis is not recommended. However, if
      recurrences are frequent or severe following documented esophageal candidiasis,
      long-term suppressive therapy with fluconazole should be considered.

PMID- 8547521
TI  - Epidemiology of Helicobacter pylori Infection. Proceedings from a roundtable
      meeting. Hertfordshire, United Kingdom, December 1994.

PMID- 8547522
TI  - Endoscopic transmission of Helicobacter pylori.
AB  - The contamination of endoscopes and biopsy forceps with Helicobacter pylori
      occurs readily after endoscopic examination of H. pylori-positive patients.
      Unequivocal proof of iatrogenic transmission of the organism has been provided.
      Estimates for transmission frequency approximate to 4 per 1000 endoscopies when
      the infection rate in the endoscoped population is about 60%. Iatrogenic
      transmission has also been shown to be the cause of the so-called 'acute mucosal
      lesion' syndrome in Japan. Traditional cleaning and alcohol rinsing is
      insufficient to eliminate endoscope/forceps contamination. Only meticulous
      adherence to disinfection recommendations guarantees H. pylori elimination.

PMID- 8547523
TI  - The relationship between gastric cancer frequency and the ratio of gastric to
      duodenal ulcer.
AB  - An international comparison of the ratio of mortality rates from gastric and
      duodenal ulcers (GU/DU) reveals a positive correlation with gastric carcinoma
      death rates. This correlation is driven by the rates of gastric ulcer and has
      decreased in recent decades. Genetic susceptibility factors appear to be involved
      in the pathogenesis of peptic ulcers: non-secretor phenotypes of blood groups
      predispose to both types of peptic ulcers, while blood group A predominates in
      gastric ulcer and group O in duodenal ulcers. Environmental factors such as
      smoking increase the risk for both types of ulcers while excessive salt intake
      increases the risk of gastric ulcer only. Such aetiological factors may modulate
      the outcome of Helicobacter pylori infection. Factors associated with duodenal
      ulcer lead to a non-atrophic diffuse antral gastritis while those associated with
      gastric ulcer lead to multifocal atrophic gastritis. The latter, but not the
      former, type of gastritis provides a micro-environmental favouring neoplastic
      transformation of the gastric epithelium.

PMID- 8547524
TI  - Accuracy of diagnostic methods used for epidemiological studies of Helicobacter
      pylori.
AB  - Epidemiological studies involve groups of individuals, or whole populations, many
      or most of whom are not ill. Clinical investigation has an individual perspective
      and precise statements need to be made about the individual alone. Serological
      methods are most commonly used for population-based epidemiological studies. Non
      invasive epidemiological methods, using breath tests or the study of saliva or
      urine, are increasing in use. All methods depend on accuracy in identifying
      presently infected or non-infected persons, and accuracy in defining a previously
      infected person. The performance of serological methods varies with the antigens
      chosen, the population from which reference sera are drawn, age, ethnicity, and
      homologous and heterologous infection rates in the population being studied. Much
      of the standardization of epidemiological assays has been done in adults, which
      means that for children there is still uncertainty concerning standards and cut
      off values. Because of differences in strains of H. pylori in different
      geographical areas, antigen selection is important when geographical comparisons
      are made. The sensitivity and specificity of a test is not strongly affected by
      the prevalence of infection. However, as the prevalence rises in the tested
      populations, the reported positive predictive value rises, and the negative
      predictive value falls. Depending on the patient population studied, accuracy
      varies with changes in the prevalence, and its magnitude depends both on the
      sensitivity and specificity. Accuracy is therefore not a very useful measure. It
      is better to look at the sensitivity and specificity, and the prevalence in the
      study, where they are measured. An alternative to separating test results into
      two or three categories is to report likelihood ratios, which report the
      probability of a person with a particular result being truly positive compared
      with the probability of a person with that result being truly negative. A
      receiver operating characteristic (ROC) curve, which describes the effect of
      varying the cut-off value on the performance of a test, can be useful in
      comparing the performance of two or more different tests. The use of multiple
      tests to augment positive culture as a 'gold standard', has been aided by use of
      polymerase chain reactions and other molecular biological methods. However, this
      augmentation has its limitations, since each of the additional methods may
      produce false positives. For example, polymerase chain reactions can be falsely
      positive if instruments are contaminated. There are people with more than one
      strain of Helicobacter pylori in the stomach, and, without molecular biological
      efforts, or serological typing tests, the 'gold standard' does not deal with
      multiple infections.

PMID- 8547525
TI  - Temporal trends and geographical variations of peptic ulcer disease.
AB  - The present review describes the time trends and geographical variations of
      peptic ulcer disease. The study of the epidemiology of peptic ulcer is a
      worthwhile scientific endeavour, because it provides the necessary background
      against which hypotheses about the aetiology of the disease can be tested. For
      individual subjects, the risk of developing peptic ulcer depends upon their date
      of birth. The risk of developing peptic ulcer has risen in generations, i.e.
      birth-cohorts, born before the turn of the century, and declined in all
      subsequent generations. The birth-cohorts with the highest risk of developing
      gastric ulcer were born 10-20 years before those with the highest risk for
      duodenal ulcer. The birth-cohort pattern of peptic ulcer disease is found to be
      similar in all European countries, the USA, Australia and Japan. In gastric
      ulcer, the birth-related risk involves all ages over 5 years, while in duodenal
      ulcer it does not start before the age of 15 years. Gastric and duodenal ulcer
      are both characterized by marked geographical variations that are similar for
      both types. The similarity in geographical variation is shared by both sexes and
      all age groups older than 5 or 15 years in case of gastric and duodenal ulcer,
      respectively. The existence of a birth-cohort phenomenon implies that exogenous
      risk factors are responsible for the occurrence of peptic ulcer and that subjects
      are exposed to these risk factors during a limited period of their childhood or
      early adulthood. As the amount of exposure changes over time, consecutive
      generations come to reflect the varying amounts of exposure and risk for
      developing the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547526
TI  - The prevalence of Helicobacter pylori infection in different countries.
AB  - The prevalence of Helicobacter pylori infection in a community is related to
      three factors: firstly, the rate of acquisition of infection with H. pylori--that
      is, incidence; secondly, the rate of loss of the infection; thirdly, the
      prolonged persistence of the bacterium in the gastroduodenal mucosa between
      infection and eradication. Variation in the prevalence of H. pylori is dominated
      by the great differences between communities in the incidence of H. pylori
      infection during childhood. The countries of the world form two groups: Group One
      is made up of those where the majority of children become infected with H. pylori
      during childhood and chronic infection continues during adult life; in Group Two
      only a minority of children are infected during childhood, but the prevalence of
      infection rises in proportion to age during adult life. Understanding the ages at
      which people acquire infection with H. pylori is crucial to the interpretation of
      H. pylori prevalence data.

PMID- 8547527
TI  - Do socio-economic status, marital status and occupation influence the prevalence
      of Helicobacter pylori infection?
AB  - AIMS: To review the influence of three factors on the prevalence of Helicobacter
      pylori infection: socio-economic status, marital status and occupation. METHODS:
      MEDLINE searches were performed using the Medical Subject Headings: Helicobacter
      pylori and socio-economic status, couples, children, transmission and occupation.
      All relevant articles were reviewed and scrutinized for further references.
      CONCLUSIONS: Lower socio-economic status and/or a low level of education are
      associated with an increase in the prevalence of H. pylori infection. There is no
      evidence that H. pylori is sexually transmitted and cohabitation among adult
      individuals is not a risk factor for transmission. A few studies suggest that the
      presence of (young) children may be required for spread within families. Data on
      occupational risk of H. pylori infection are sparse. Gastroenterologists and
      other health care workers may be at increased risk but the data are not
      conclusive.

PMID- 8547528
TI  - The incidence of Helicobacter pylori infection.
AB  - Acute Helicobacter pylori infection invariably passes undetected. Consequently,
      the incidence of infection has been determined indirectly from epidemiological
      studies. In adults of industrialized countries, an estimated 0.5% of the
      susceptible population becomes infected each year. This incidence has been
      decreasing over time. Thus, adults who currently harbour the organism are more
      likely to have been infected in childhood than adulthood. The incidence of H.
      pylori infection continues to be high (between 3% and 10% per year) in developing
      countries. Throughout the world, incidence of H. pylori infection appears to be
      higher in children than in adults, possibly due to lower standards of personal
      hygiene in younger populations.

PMID- 8547529
TI  - Prevalence of Helicobacter pylori in non-ulcer dyspepsia.
AB  - Dyspepsia is a poorly understood term that is used to describe symptoms that
      originate in the upper gastrointestinal tract. There is increasing evidence that
      Helicobacter pylori infection plays an aetiological role in some forms of
      dyspepsia. H. pylori infection is more common in dyspeptic patients than
      asymptomatic controls. Clinical trials of the benefit of H. pylori eradication
      therapy in non-ulcer dyspepsia have given conflicting results. This may be due to
      methodological flaws in the studies to date. Trials in non-ulcer dyspepsia may
      have several end-points. Future studies should be long-term, placebo-controlled,
      double-blind, and use a validated symptom questionnaire. Acid secretion studies
      demonstrate acid hypersecretion in non-ulcer dyspepsia that is intermediate
      between that seen in duodenal ulcers and asymptomatic carriers. This suggests
      that H. pylori gastritis represents a spectrum of disease that includes duodenal
      ulceration, whose natural history is one of relapses and remissions, and non
      ulcer dyspepsia.

PMID- 8547530
TI  - The prevalence of Helicobacter pylori in peptic ulcer disease.
AB  - Both duodenal and gastric ulcer disease are closely associated with Helicobacter
      pylori infection. An infected individual has an estimated lifetime risk of 10-20%
      for the development of peptic ulcer disease, which is at least 3-4 fold higher
      than in non-infected subjects. H. pylori infection can be diagnosed in 90-100% of
      duodenal ulcer patients and in 60-100% of gastric ulcer patients. Subjects
      infected with a cytotoxin-producing bacterial strain, or a strain possessing
      cagA, are at a higher risk of duodenal ulcer. Other factors that may influence
      the peptic ulcer risk in infected subjects are the amount of gastric acid
      production (which is increased in duodenal ulcer disease and decreased in gastric
      ulcer disease), the presence of gastric metaplasia in the duodenal bulb, smoking,
      and genetic factors (e.g. blood group O and lack of the secretor gene). After
      eradication of the infection, the risk of recurrence of ulcer disease is reduced
      to below 10% for gastric ulcer disease and to approximately 0% for duodenal ulcer
      disease.

PMID- 8547531
TI  - The prevalence of Helicobacter pylori infection in gastric cancer.
AB  - The prevalence of Helicobacter pylori infection in gastric cancer patients is
      difficult to estimate because the infection may be lost from individuals with
      cancer or its precursor conditions. The bacterium does not colonize cancerous
      tissue and therefore studies using histopathology as a means of assessing
      infection require gastric biopsy material sampled separately from the tumour
      itself. Results from five such studies, with more than 50 patients, have
      demonstrated an H. pylori prevalence of 43%-78%. Studies using serological
      assessment of antibody presence have the advantage of enabling adequate case
      control comparisons. Ten reported studies that were retrospective in design
      showed a range in prevalence from 52% to 89% among the cases and from 38% to 78%
      among the controls. Five studies showed a significant increase in infection
      prevalence among the cases, with odds ratios ranging from 1.6 to 4.2. The odds
      ratio increased in subjects who were younger. Retrospective studies may be biased
      in that the prevalence of H. pylori among cases may be systematically under
      estimated. Three prospective serological studies showed a prevalence of 69%-95%
      among cases and 47%-76% among controls. All three studies had a significantly
      elevated odds ratio and a pooled estimate of this was 3.8 (95% CI: 2.3-6.2). In
      the pooled analysis there was a significant trend towards an increased odds ratio
      with increased time between the assessment of infection and cancer diagnosis.
      After 14 years of follow-up the overall infection prevalence among cases was 90%
      and the odds ratio was 8.7 (95% CI: 2.7-45.0). This might represent the best
      estimate of infection prevalence and associated risk.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8547532
TI  - The epidemiology and transmission of Helicobacter pylori infection in children.
AB  - How and when Helicobacter pylori infection is acquired is unknown. Faecal-oral
      and oral-oral transmission have been demonstrated in animal studies of other
      Helicobacter species, whilst sero-epidemiological studies in adults show a cohort
      effect suggesting that primary acquisition occurs in childhood. H. pylori can be
      detected non-invasively using serology or the 13C-urea breath test, and although
      the accuracy of both methods is well established in adults, further validation
      studies are needed in children, especially those under 5 years old. In children,
      the age-specific prevalences of H. pylori, which are low in developed countries
      and high in developing countries, suggest that in most cases infection is
      acquired early in life. Prospective studies show that the incidence of H. pylori
      infection in adults is about 0.4% per year; in children, studies using the 13C
      urea breath test demonstrate incidences in developing and developed countries of
      36% and 2.7% per year, respectively. Intra-familial clustering of H. pylori and
      high prevalences in orphanages and institutions for the mentally retarded suggest
      that person-to-person transmission of H. pylori is important. In addition, H.
      pylori infection has been associated with poor childhood socio-economic
      conditions--with overcrowding and close person-to-person contact through bed
      sharing being the most consistent and significant associations. However, these
      studies are liable to recall-bias. Since it is still unclear whether H. pylori is
      transmitted by the faecal-oral or oral-oral routes, it is possible that both
      routes exist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547533
TI  - Transmission of Helicobacter pylori: faecal-oral versus oral-oral route.
AB  - Helicobacter pylori is one of the most common bacteria responsible for chronic
      infection worldwide. Its reservoir is essentially human. The transmission of H.
      pylori seems to be direct from person-to-person, however, a common source cannot
      be totally excluded. Two routes of transmission have been proposed: faecal-oral
      and oral-oral, based on the following arguments: H. pylori has been cultured from
      faeces and seems to survive in water in non-culturable forms. Although certain
      epidemiological studies have suggested waterborne and foodborne transmission,
      there has been no confirmation of this. H. pylori has been cultured from the oral
      cavity in several studies and there is some indirect but scarce evidence for oral
      oral transmission. Further study of its molecular epidemiology should provide
      greater insights into this as yet unsolved question.

PMID- 8547534
TI  - Non-human reservoirs of Helicobacter pylori.
AB  - Early attempts to identify non-human reservoirs for Helicobacter pylori were
      largely unrewarding. The one exception being old-world macaques, which were found
      to be colonized with H. pylori; however, it is doubtful whether this species
      provides an important reservoir for human infection. The possibility of other
      animal reservoirs and zoonotic transmission of H. pylori has been discussed, but
      until recently has not received serious study. Enthusiasm to initiate extensive
      studies in this area were further dampened by the inability to experimentally
      infect several different species of mammals with the organism. Reports using
      whole-cell enzyme-linked immunoabsorbent assay (ELISA) sonicate to monitor
      infection serologically, have cited a high incidence of H. pylori infection in
      abattoir workers. These results have been criticized because of potential
      antigenic cross-reactivity in workers' sera due to the constant exposure of these
      personnel to other gastrointestinal flora of animals. The large spiral gastric
      Helicobacter-like organisms (GHLOs) commonly noted in dogs and cats are
      associated with approximately 0.08-1% of gastritis in humans. These GHLOs often
      infect patients who own pets, suggesting a zoonotic link. Thus, the recent
      isolation of H. pylori from the inflamed gastric mucosa of commercially reared
      cats, and the ability to experimentally infect cats with H. pylori, raises the
      possibility of zoonotic H. pylori transmission from infected animals who have
      close human contact. Water and raw vegetables have been linked with H. pylori
      transmission in a few epidemiologically-based studies in developing populations.
      The recent isolation of H. pylori from the faeces of adults and children
      implicates a faecal-oral transmission pathway and supports the theory that both
      food and water (via faecal contamination) could be a source of H. pylori.
      Providing conclusive evidence that H. pylori has the ability to exist in the
      environment as a viable, non-culturable coccoid form that can replicate after
      ingestion by a mammalian host would considerably strengthen the hypothesis that
      water and food are important H. pylori reservoirs. The existence and extent of
      these reservoirs in nature, and the manner in which they interact with humans,
      will provide important new insights into understanding the epidemiology of this
      worldwide infection.

PMID- 8547535
TI  - Childhood leukemia in metropolitan regions in the United States: a possible
      relation to population density?
AB  - Following recent research in Great Britain, the geographic incidence of leukemia
      and non-Hodgkin's lymphoma among White children in three metropolitan regions of
      the United States (San Francisco-Oakland, CA; Detroit, MI; and Atlanta, GA)
      during 1978-82 has been analyzed using census tract-specific data. There was no
      evidence of a general tendency for cases to cluster geographically, in contrast
      to results from Britain. Further, rates did not vary with median income or
      education levels for census tracts. However, there was a statistically
      significant increasing trend in incidence rates with increasing population
      density: relative risk for highest relative to lowest category = 1.4 (95% percent
      confidence interval [CI] = 1.1-2.0) for White population density, and 1.4 (CI =
      1.0-2.0) for total population density. The interpretation of these findings is
      unclear and further investigation is required. It is possible that population
      density is acting as a surrogate for some virus-related factor.

PMID- 8547536
TI  - A case-control study of maternal risk factors for thyroid cancer in young women
      (California, United States).
AB  - A population-based case-control interview study investigated whether reproductive
      factors are related to the striking female-over-male excess of thyroid cancer
      among women of reproductive age in Los Angeles County, CA (United States). As a
      separate component of that study, mothers of 153 cases and 140 controls who were
      age 40 or younger at diagnosis or reference date were interviewed by telephone to
      determine the significance of family and maternal risk factors in the subsequent
      development of thyroid cancer among the daughters. More case than control mothers
      experienced miscarriage prior to the index pregnancy (odds ratio [OR] = 2.0, 95
      percent confidence interval [CI] = 1.1-3.5). Increased risk was associated with
      family history of thyroid cancer or other thyroid disease (OR = 2.1, CI = 1.2
      3.6). More control than case mothers smoked during the index pregnancy (OR = 0.6,
      CI = 0.4-1.0); however, among mothers who smoked, case mothers smoked more. Case
      mothers experienced a greater increase in weight from minimum adult weight to
      weight at index pregnancy (P for trend = 0.01). Reports from mothers also
      confirmed the risk associated with the daughter's exposure to ionizing radiation
      from birth through adolescence; ionizing radiation remains the best-established
      risk factor for thyroid cancer.

PMID- 8547537
TI  - Physical activity, medical history, and risk of testicular cancer (Alberta and
      British Columbia, Canada).
AB  - In order to evaluate risk factors for germ cell cancers, we conducted a case
      control study of 510 men with testicular cancer aged 15 to 79 years and 996
      randomly selected age-matched controls in the provinces of British Columbia and
      Alberta, Canada. Subjects completed a mailed questionnaire providing data on
      education level, ethnic origin, medical history, smoking, occupation, and
      recreational and sports activity. The response rate among cases was 80.3 percent
      and among controls was 68.1 percent. After controlling for age and ethnic origin,
      undescended testis was associated positively with risk of testicular cancer (odds
      ratio [OR] = 3.5; 95 percent confidence interval [CI] = 2.2-5.7) as was inguinal
      hernia requiring surgery (OR = 2.0, CI = 1.3-2.9), and hydrocoele (OR = 2.6, CI =
      1.4-5.1). Risk of testicular cancer increased with height, with subjects taller
      than 180 cm having a significantly increased risk compared with those 174 cm or
      less (OR = 1.5, CI = 1.1-2.1). A moderate to high level of recreational activity
      level was associated inversely with testicular cancer risk (OR = 0.6, CI = 0.5
      0.8).

PMID- 8547538
TI  - Interaction of family history of breast cancer and dietary antioxidants with
      breast cancer risk (New York, United States).
AB  - We sought to determine if specific dietary antioxidants may be particularly
      effective in reducing breast cancer risk for women reporting family history (FH)
      of breast cancer in a first-degree relative. Interviews regarding usual diet,
      health, and family histories were conducted with 262 premenopausal and 371
      postmenopausal women with incident, primary breast cancer from western New York
      (United States). These women were frequency-matched by age and county of
      residence with community controls. Among premenopausal women, there was a
      significant interaction between FH and alpha-tocopherol; alpha-tocopherol was
      associated with significantly decreased risk among FH+ women (adjusted fourth
      quartile odds ratio [OR] = 0.01, 95 percent confidence interval [CI] = 0.0-0.3).
      This association was much weaker for FH- women [OR = 0.7, CI = 0.4-1.2]. For FH-
      women, a significant inverse association was observed between beta-carotene and
      premenopausal breast-cancer risk (OR = 0.4, CI = 0.3-0.5), but not for FH+ women
      (OR = 0.5, CI = 0.1-4.0). Similar relationships, although not as strong, were
      noted among postmenopausal women. Although limited by small numbers, these
      results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and
      FH- women, and that alpha-tocopherol may be a potential chemopreventive agent for
      women with a family history of breast cancer, particularly premenopausal women.

PMID- 8547539
TI  - Exogenous hormone use and the risk of postmenopausal breast cancer: results from
      The Netherlands Cohort Study.
AB  - The association between the use of exogenous hormones as either oral
      contraceptives (OC) or hormone replacement therapy (HRT) in relation to
      postmenopausal breast cancer incidence was examined in the Netherlands Cohort
      Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types
      of exogenous hormone use and other risk factors was collected by mailed
      questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases
      were identified. After adjustment for traditional breast cancer risk factors, the
      relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI]
      = 0.79-1.48) for women who ever used OCs cf women who never used OCs. The
      relative rates (with CIs) for women who used OCs for a period < 5 years, 5-9
      years, 10-14 years, and 15+ years were 0.97 (0.61-1.55), 1.20 (0.69-2.07), 1.03
      (0.60-1.77), and 1.96 (0.99-3.89), respectively. The test for trend was not
      significant (P = 0.13). There was no evidence of any association between the
      number of years between the first and the last use of OCs and breast cancer
      incidence. In the subgroup of women with first-degree relatives with breast
      cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI =
      0.67-3.41), whereas in the remaining women, the RR was 0.97 (CI = 0.73-1.27).
      Ever-use of HRT compared with never-use was not associated with an increase in
      breast cancer risk in the multivariate analysis (RR = 0.99, CI = 0.68
      1.43).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547540
TI  - The accuracy of prostate cancer staging in a population-based tumor registry and
      its impact on the black-white stage difference (Connecticut, United States).
AB  - Stage at diagnosis of prostate cancer is a major determinant of survival. Among
      Blacks, prostate cancer is diagnosed at a later stage of disease than among
      Whites. This study examined the accuracy of routine coding of prostate cancer
      stage in the Connecticut (United States) Tumor Registry (CTR) and its effect on
      the Black/White stage difference. Medical records were collected for 115 Black
      and 136 White men with prostate cancer diagnosed between 1987 and 1990. Stage at
      diagnosis was determined by a panel of two of the study members and compared with
      the stage in the CTR file. According to the panel, 32 percent of Blacks, but only
      15 percent of Whites, were diagnosed with distant stage disease. Fifty-eight
      cases (26 percent of Whites and 20 percent of Blacks) were staged incorrectly by
      the CTR. Two-fifths of the errors were due to incomplete medical records at the
      CTR and three-fifths were due to CTR coding or data management errors. The more
      accurate staging did not have an appreciable impact on the Black/White stage
      difference. Further work is needed to characterize the accuracy of routinely
      coded cancer registry stage data for different cancer sites, to devise ways of
      improving accuracy, and to determine the impact of staging inaccuracies on
      research that utilizes these data.

PMID- 8547541
TI  - A nested case-control study of mammographic patterns, breast volume, and breast
      cancer (New York City, NY, United States).
AB  - The relations of Wolfe mammographic patterns, quantitative mammographic
      densities, and mammographically estimated breast size to breast cancer risk were
      investigated prospectively in a case-control study nested in the New York
      University Women's Health Study, a cohort of 14,291 women in New York City, NY
      (United States). The archived mammograms of 197 breast cancer cases who were
      identified during the first 5.5 years of the study and of 521 individually
      matched controls from the same cohort were retrieved and classified according to
      Wolfe parenchymal patterns and mammographic densities by two expert radiologists.
      Breast size and volume were estimated on the mammogram's cranio-caudal
      projection. In both premenopausal and postmenopausal subjects, the risk of breast
      cancer increased progressively with increasing density and percent density area.
      A significantly increased risk was found also for Wolfe pattern DY in
      premenopausal women and P2 pattern in postmenopausal subjects. In premenopausal
      women, mammographically determined breast volume and breast height also were
      associated positively with breast cancer risk. Although the results of the
      present study confirmed that mammographic parenchymal patterns and densities were
      important predictors of breast cancer risk, their practical use in screening
      seems limited due to the high prevalence of high risk patterns.

PMID- 8547542
TI  - Thyroid cancer incidence in Asian migrants to the United States and their
      descendants.
AB  - We compared incidence rates of primary cancer of the thyroid among United States
      born and foreign-born Chinese, Japanese, and Filipino residents of the US with
      rates among US-born Whites. Thyroid cancers diagnosed between 1973 and 1986
      occurring among individuals 15 to 84 years of age residing in western Washington
      state, the San Francisco-Oakland (California) area, or the state of Hawaii were
      included in the analysis. Population estimates by age, gender, ethnicity, and
      country of birth were obtained for these areas from the US Bureau of the Census.
      Filipino women born in the Philippines had 3.2 (95 percent confidence interval =
      2.7-3.8) times the rate of thyroid cancer of US-born White women, while US-born
      Filipino women were not at any increased risk. Philippine-born Filipino men also
      had a relatively high rate of thyroid cancer (relative risk [RR] = 2.6), more so
      than US-born Filipino men (RR = 1.5). Among Japanese, risk of thyroid cancer
      varied by birthplace, but the direction of the association differed by gender and
      by histologic type of cancer. No clear association with birthplace was noted
      among Chinese men or women. These data suggest that persons residing in one or
      more regions from which Filipino-Americans migrated have been exposed to
      environmental influences that have increased their subsequent risk of thyroid
      cancer.

PMID- 8547543
TI  - Childhood leukemia and rural population movements: Greece, Italy, and other
      countries.
AB  - Mortality from childhood leukemia was examined particularly in rural countries in
      relation to any major rural-urban migration. Significant increases have been
      found in other situations of rural population mixing as predicted by the
      infection hypothesis. The 1950s and 1960s were of most interest since it preceded
      the decline in mortality brought about by effective chemotherapy in many
      countries. The 33 countries covered were all those in the World Health
      Organization's mortality database. No sensitive measure of rural-urban migration
      is available for international comparisons. However, it seems noteworthy that
      Greece and Italy, the two countries with the most striking levels of rural
      migration in the 1950s and 1960s, also had unusually high mortality rates from
      childhood leukemia. Greece was most affected proportionally by these population
      movements and from 1958 to 1972 had the highest recorded mortality from this
      cause in the world. The problems of international comparisons of mortality data
      dictate caution in drawing conclusions. However, against a background of other
      work on population mixing, and in the light of certain considerations, we suggest
      that the marked rural population mixing in Greece and Italy may have contributed
      to their high mortality rates from childhood leukemia in the 1950s and 1960s.

PMID- 8547544
TI  - Proportional melanoma incidence and occupation among white males in Los Angeles
      County (California, United States).
AB  - A case-control analysis of cancer registry data was used to examine the
      hypothesis that occupational exposure to sunlight influences the risk of
      melanoma. Occupation at diagnosis was available for 3,527 cutaneous melanomas and
      53,129 other cancers identified by the Los Angeles County (California, United
      States) Cancer Surveillance Program among non-Spanish-surnamed White males aged
      20 to 65 years between 1972 and 1990. Occupational exposure to sunlight was
      assessed by blinded expert coding of job titles as indoor, outdoor, and mixed
      indoor/outdoor. Relative to indoor occupations, proportionate odds ratios (OR)
      adjusted for age, level of education, and birthplace were 1.16 (95 percent
      confidence interval [CI] = 1.07-1.27) for indoor/outdoor occupations and 1.15 (CI
      = 0.94-1.40) for outdoor occupations. However, increasing levels of the education
      or training required for the occupation was associated more strongly with
      increased melanoma occurrence (ORs adjusted for age, occupational sun exposure,
      and birthplace, were 1.0, 1.63, 2.09, 2.23, and 2.99 for low-skill occupation,
      high school, college, postgraduate, and doctoral levels, respectively). Analysis
      of melanoma occurrence by job titles confirmed a clear variation by the required
      education or training level but not by the category of occupational sunlight
      exposure. The findings suggest that lifestyle factors associated with higher
      levels of education may be more important determinants of melanoma risk than
      characteristics of the work environment.

PMID- 8547545
TI  - Spontaneous abortion and risk of fatal breast cancer in a prospective cohort of
      United States women.
AB  - Controversy exists over the possible relationship between induced and spontaneous
      abortion and risk of breast cancer. Thus, the association of fatal breast cancer
      and spontaneous abortion was examined in a large prospective study of United
      States adult women. After seven years of follow-up, 1,247 cases of fatal breast
      cancer were observed among 579,274 women who were cancer-free at interview in
      1982 and who provided complete reproductive histories. Results from Cox
      proportional hazards models, adjusted for other risk factors, showed no
      association between a history of spontaneous abortion and risk of fatal breast
      cancer (rate ratio [RR] = 0.89, 95 percent confidence interval [CI] = 0.78-1.02).
      The RR did not increase with increasing numbers of abortions. Parous women who
      had a spontaneous abortion before their first term birth were not at increased
      risk compared with parous women with no history of spontaneous abortion (RR =
      0.76, CI = 0.54-1.05). Women whose only pregnancy ended in a spontaneous abortion
      were not at increased risk compared with women who were never pregnant (RR =
      0.61, CI = 0.27-1.38) or whose only pregnancy ended in a livebirth (RR = 0.72, CI
      = 0.32-1.65). These findings do not support an association between spontaneous
      abortion and fatal breast cancer.

PMID- 8547546
TI  - A comparison of amrinone with sodium nitroprusside for control of hemodynamics
      during infrarenal abdominal aortic surgery.
AB  - OBJECTIVES: The control of hemodynamic changes during surgical resection of
      abdominal aortic aneurysms (AAA) remains a challenge to anesthesiologists. In the
      past, hypertensive episodes have been treated with sodium nitroprusside (SNP).
      However, amrinone may provide some benefits when compared with SNP because of its
      positive inotropic and vasodilatory properties. Therefore, the purpose of this
      study was to compare amrinone with SNP for hemodynamic control during AAA
      surgery. DESIGN: This study was a prospective, randomized investigation. SETTING:
      This study was performed at a single university hospital. PARTICIPANTS: This
      study included 20 patients undergoing AAA resection. INTERVENTIONS: After
      institutional review board approval, participants were randomized to receive
      either SNP (group N = 10) or amrinone (group A = 10). Both agents were started 10
      minutes before aortic cross-clamping and discontinued 10 minutes before
      unclamping. Anesthesia was induced with thiopental or etomidate and maintained
      with oxygen, nitrous oxide, isoflurane, fentanyl, and vecuronium. Hemodynamic
      measurements included heart rate, systolic and diastolic blood pressure, cardiac
      output, systolic and diastolic pulmonary artery pressure, pulmonary capillary
      wedge pressure, central venous pressure, mixed venous oxygen saturation,
      electrocardiogram, and ST-T wave trend analysis. MEASUREMENTS AND MAIN RESULTS:
      Demographic and clinical characteristics for the two groups were similar. Mixed
      venous oxygen saturation was significantly lower (p < 0.05) in group N
      immediately after unclamping. There were no differences between groups for the
      other measurements studied. There were no episodes of myocardial ischemia in
      either group. CONCLUSIONS: This study demonstrates that amrinone provides
      equivalent hemodynamic control to SNP during abdominal aortic aneurysm surgery
      because it allows moderate reductions in blood pressure without affecting other
      hemodynamic measurements. Further studies are needed to assess whether patients
      with poor preoperative left ventricular function would benefit from amrinone
      management during AAA resection.

PMID- 8547547
TI  - Isoflurane versus sodium nitroprusside for the control of proximal hypertension
      during thoracic aortic cross-clamping: effects on spinal cord ischemia.
AB  - OBJECTIVE: This study was designed to compare the effects of isoflurane and
      nitroprusside on spinal cord ischemia when they are used to control proximal
      hypertension during thoracic aortic cross-clamping (TACC). DESIGN: Prospective,
      randomized, blinded experimental study. SETTING: Laboratory and animal research
      facility. PARTICIPANTS: Adult mongrel dogs. INTERVENTIONS: Two groups of eight
      dogs had TACC for 45 minutes. Proximal aortic, distal aortic, and cerebrospinal
      pressure was calculated as the distal mean pressure minus the CSF pressure. Group
      1 received nitroprusside and group 2 received isoflurane to control proximal
      hypertension during cross-clamping. The dogs were neurologically evaluated 24 and
      48 hours later by an observer blinded as to the study group. Spinal cord segments
      were obtained for histopathologic examination. MEASUREMENTS AND MAIN RESULTS:
      Distal perfusion pressure and spinal cord perfusion pressure were significantly
      higher in the isoflurane group (p < .005). At 24 hours, seven of eight dogs in
      group 1 had severe neurologic injury (ie, paraplegia), with the eight having mild
      neurologic injury. This is in contrast to group 2, where 6 of 8 dogs had either
      minimal or no injury, one had mild injury, and one had severe injury. Similar
      results were observed at 48 hours (p < .005). CONCLUSIONS: Isoflurane, when used
      to control proximal hypertension during TACC, produces a higher spinal cord
      perfusion pressure and is associated with a lower incidence of neurologic injury
      than nitroprusside in this canine model.

PMID- 8547548
TI  - Increased left ventricular contractility during cross-clamping of the descending
      thoracic aorta.
AB  - OBJECTIVE: To evaluate how left ventricular (LV) dimensions and contractility and
      proximal systemic hemodynamics respond during and after 30 minutes of cross
      clamping of the descending thoracic aorta. DESIGN: The study was prospective and
      controlled. SETTING: The study was performed in a university animal laboratory.
      PARTICIPANTS: Ten pigs (bodyweight: 22 to 30 kg). INTERVENTIONS: The pigs were
      anesthetized with fentanyl and ketamine, and the heart and aorta were exposed
      through a left thoracotomy. The aortic root pressure and flow and LV dimensions
      were monitored with a high-fidelity pressure catheter, a precalibrated ultrasonic
      transit-time flow probe, and by two-dimensional ultrasound imaging, respectively.
      MEASUREMENTS AND MAIN RESULTS: After 1 minute of cross-clamping, LV end-diastolic
      and end-systolic diameters were increased 17% and 32% above baseline (both p <
      0.001), respectively, whereas LV fiber shortening was decreased by 35% (p < 0.05)
      corresponding to the 257% increase in wall stress (p < 0.001). After 5 minutes,
      LV dimensions, fiber shortening, and wall stress had returned to baseline levels.
      After 10 minutes, fiber shortening was increased 67% (p < 0.05), although wall
      stress was maintained at baseline levels. Simultaneously, the aortic mean blood
      pressure, heart rate, and cardiac output peaked 112% (p < 0.001), 81% (p <
      0.001), and 125% (p < 0.01) above baseline, respectively. CONCLUSIONS: Cross
      clamping grossly increased systemic afterload grossly and was followed by
      moderate LV dilation, which resolved after 5 minutes owing to the combined
      effects of proximal vasodilation, increased myocardial contractility, and
      tachycardia. This hyperdynamic circulatory state was maintained during cross
      clamping and decreased after declamping.

PMID- 8547549
TI  - Effects of thoracic epidural analgesia on coronary hemodynamics and myocardial
      metabolism in coronary artery bypass surgery.
AB  - OBJECTIVE: A possible influence of thoracic epidural analgesia on coronary
      hemodynamics and myocardial metabolism in coronary artery bypass grafting was
      investigated. DESIGN: The study was prospective and randomized. SETTING: The
      study was performed in a university hospital. PARTICIPANTS: Thirty male patients
      less than 65 years of age and with ejection fraction greater than 0.5
      participated. They were randomized into 3 groups: the high fentanyl (HF) group
      receiving high-dose fentanyl (55 micrograms/kg) anesthesia, the HF + thoracic
      epidural analgesia (TEA) group receiving the same general anesthesia plus
      thoracic epidural analgesia, and the low-fentanyl (LF) + TEA group receiving low
      dose fentanyl (15 micrograms/kg) anesthesia plus thoracic epidural analgesia.
      INTERVENTIONS: A thoracic epidural catheter, a peripheral and central venous
      catheter, a radial artery catheter, a thermodilution pulmonary artery catheter,
      and a coronary sinus reverse thermodilution catheter were inserted. MEASUREMENTS
      AND MAIN RESULTS: Coronary circulatory parameters, myocardial oxygenation, and
      myocardial substrate utilization were investigated before bypass and for 9 hours
      after bypass. Before bypass, the most striking finding was a reduction in
      myocardial lactate extraction in all groups, but also coronary flow and
      myocardial oxygen consumption decreased compared with baseline. After bypass, the
      only significant finding was a lower coronary vascular resistance early
      postoperatively in the epidural groups, but coronary blood flow was adequate in
      all groups. Myocardial metabolism was essentially unchanged both with and without
      epidural analgesia after bypass. CONCLUSION: With regard to the coronary
      circulation and myocardial metabolism, no hard data supporting the use of
      thoracic epidural analgesia in coronary artery bypass grafting were found.

PMID- 8547550
TI  - Relationship between tissue ischemia and venous endothelin-1 during abdominal
      aortic aneurysm surgery.
AB  - OBJECTIVES: Several substances may be released from ischemic tissues with the
      declamping shock that occurs during abdominal aortic aneurysm surgery. To clarify
      the relationship between tissue ischemia and venous endothelin-1 (ET-1) level in
      humans, plasma ET-1 and oxygen content in the iliac vein were measured before
      anesthesia, after the induction of anesthesia, after the release of the proximal
      and first distal clamps, after the release of the second distal clamp, and 1 hour
      after the second clamping. DESIGN: Prospective study. SETTING: A University
      hospital. PARTICIPANTS: Seven patients who underwent abdominal aneurysmectomy and
      replacement with bifurcated graft. INTERVENTIONS: A 20G catheter was inserted
      into the radial artery for the direct measurement of blood pressure and for
      collecting arterial blood. An 18G, 20-cm catheter was inserted into the femoral
      vein for collecting venous blood from the lower extremities. MEASUREMENTS AND
      MAIN RESULTS: The arterial and venous ET-1 levels did not change after the
      induction of anesthesia. Immediately after the initial release of the proximal
      and distal clamps, venous oxygen content dramatically decreased from 11.3 to 3.6
      mL/dL (vol%) with significant increases in venous ET-1 concentration from 2.3 to
      4.9 pg/mL. Concomitant with the decrease in venous oxygen content, venous plasma
      pH and base excess decreased with increase in PCO2, suggesting that ischemic
      changes in tissues distal to the cross-clamp may occur during aortic clamping.
      Venous ET-1 levels were significantly correlated with venous oxygen content, pH,
      PO2, oxygen saturation, base excess, blood sodium concentration, and potassium
      concentration. One hour after the second declamping, the venous ET-1 level
      remained high in comparison with the preanesthetic level, whereas the venous
      oxygen content returned to the preanesthetic level. There was no correlation
      between venous plasma ET-1 and venous plasma norepinephrine or epinephrine
      concentration. CONCLUSIONS: Tissue ischemia may increase venous ET-1 levels in
      humans. Factor(s) other than tissue ischemia may provoke the increase in venous
      ET-1 that occurs after the release of the second distal clamp.

PMID- 8547551
TI  - Supraceliac, but not infrarenal, aortic cross-clamping upregulates neutrophil
      integrin CD11b.
AB  - OBJECTIVE: To evaluate the effects of supraceliac and infrarenal aortic cross
      clamping on the expression of neutrophil integrin in CD11b (a marker of systemic
      cytokine release). DESIGN: Two groups, determined by anatomic placement of aortic
      cross-clamp. Laboratory personnel were blinded as to group assignment. SETTING:
      University teaching and community hospitals. Laboratory facilities used were
      university and Veteran's Affairs medical centers. PARTICIPANTS: Patients
      scheduled for aortic surgery. INTERVENTIONS: Blood sampling was performed at
      baseline, after 30 minutes of aortic cross-clamp duration, 30 and 90 minutes
      after reperfusion (for tumor necrosis factor-alpha plasma levels in infrarenal
      cross-clamp group), and at baseline and 90 minutes reperfusion (for neutrophil
      CD11b expression quantification) in both groups. MEASUREMENTS AND MAIN RESULTS:
      Tumor necrosis factor-alpha measured by ELISA technique did not change at any
      time period in the infrarenal clamping group. Neutrophil CD11b expression,
      measured by double antibody staining and FACScan analysis, did not change
      significantly at 90 minutes of reperfusion in the infrarenal group, but increased
      significantly (p < 0.05) in the supraceliac aortic cross-clamp group. CONCLUSION:
      Neutrophil integrin CD11b has been demonstrated to be the primary adhesive
      glycoprotein responsible for neutrophil organ entrapment and subsequent
      neutrophil-mediated reperfusion injury. These results suggest that upregulation
      of neutrophil integrin CD11b after supraceliac aortic clamping may in part be
      responsible for the higher incidence of acute lung injury after thoracic aortic
      aneurysm repair requiring supraceliac clamping when compared with infrarenal
      aneurysm surgery.

PMID- 8547552
TI  - Effects of dexmedetomidine on coronary hemodynamics and myocardial oxygen
      balance.
AB  - OBJECTIVE: alpha 2-adrenergic agonists decrease central sympathetic outflow and
      maintain normal transmural myocardial blood flow distribution, but intravenous
      bolus doses of these agents can also induce excessive coronary vasoconstriction
      and myocardial ischemia. The hypothesis of the present study was that a rapid
      intravenous bolus of dexmedetomidine, a specific alpha 2-adrenergic agonist, will
      cause coronary vasoconstriction and accompanying myocardial ischemia in young
      pigs. DESIGN: Prospective, controlled study on experimental animals. SETTING:
      Animal laboratory of a university cardiorespiratory research center.
      PARTICIPANTS: Twelve domestic 8-week-old open-chest pigs, anesthetized with high
      dose fentanyl. Another six pigs served as controls. INTERVENTIONS: Sequential
      intravenous dexmedetomidine boluses of 3, 10, and 30 mg/kg were administered, and
      responses were measured during peak changes (2 minutes after injection) and
      during recovery after each dose. MEASUREMENTS AND MAIN RESULTS: Left anterior
      descending coronary artery blood flow, calculated regional coronary vascular
      resistance, myocardial extraction of oxygen and lactate, plasma catecholamine
      levels, and conventional central hemodynamic parameters were measured. The two
      higher doses of dexmedetomidine induced 21% and 29% immediate increases in left
      anterior descending coronary artery blood flow. At the same time mean systemic
      blood pressure and pulmonary capillary wedge pressure increased, and calculated
      regional coronary vascular resistance increased. Myocardial extraction of oxygen
      and lactate remained unchanged. CONCLUSIONS: Large intravenous doses of
      dexmedetomidine caused moderate regional coronary vasoconstriction without
      metabolic signs of myocardial ischemia in young domestic pigs at the same time as
      a marked vasoconstrictive response in the systemic circulation.

PMID- 8547553
TI  - Effects of alpha-adrenergic blockade on regional myocardial function in canine
      ischemic myocardium during beta-adrenergic blockade.
AB  - OBJECTIVE: The contribution of alpha-adrenergic receptor subtypes in mediation of
      coronary vasoconstriction during ischemia remains controversial. This study
      investigated the effects of alpha-adrenergic subtypes blockade on regional
      myocardial function in a canine ischemic model. DESIGN: Prospective, randomized,
      controlled trial. SETTING: Experimental animal laboratory in a university medical
      center. PARTICIPANTS: Thirty-two adult dogs, weighing 13 to 22 kg. INTERVENTIONS:
      The animals were prepared with pentobarbital, oxygen, enflurane and pancuronium.
      Two selective alpha 1-adrenergic antagonists (bunazosin, 50 micrograms/kg/min, n
      = 8, and prazosin, 25 micrograms/kg/min, n = 8) and the alpha 2-adrenergic
      antagonist (yohimbine, 15 micrograms/kg/min, n = 8) were administered after the
      partial occlusion of the left circumflex coronary artery (LCX) during beta
      adrenergic blockade (propranolol, 1 mg/kg). MEASUREMENTS AND MAIN RESULTS:
      Myocardial systolic segment shortening (%SS) and a myocardial lactate extraction
      ratio (LER) were used as indices of regional myocardial and metabolic function.
      Compared with poststenotic condition, coronary blood flow of the LCX was
      increased by 123% with bunazosin and 138% with prazosin (p < 0.05, respectively).
      Both %SS and LER in the ischemic myocardium were significantly improved after
      treatment with both alpha 1-adrenergic antagonists (in the bunazosin group, %SS,
      8.3 +/- 1.9 to 10.4 +/- 2.2%, p < 0.05; LER, -12.8 +/- 12.3 to 6.2 +/- 15.9%, p <
      0.01; in the prazosin group, %SS, 8.5 +/- 1.6 to 10.3 +/- 1.9%, p < 0.05; LER, 
      10.2 +/- 5.7 to 3.6 +/- 10.2%, p < 0.05). In contrast, coronary blood flow of the
      LCX, %SS and LER were not different from poststenotic condition during alpha 2
      adrenergic receptor blockade with yohimbine. The salutary effect of bunazosin was
      also observed after mechanically controlling for the afterload reduction produced
      by alpha 1-adrenergic blockade (n = 8). Prazosin and yohimbine were found to
      produce a significant increase in plasma norepinephrine levels in contrast to
      bunazosin, which had no significant effect. CONCLUSIONS: These data indicate that
      alpha 1-adrenergic blockade increases coronary blood flow and improves regional
      myocardial function during myocardial ischemia.

PMID- 8547554
TI  - Pain outcomes after thoracotomy: lumbar epidural hydromorphone versus
      intrapleural bupivacaine.
AB  - OBJECTIVE: To evaluate postthoractomy analgesia in patients receiving lumbar
      epidural hydromorphone versus intrapleural bupivacaine. DESIGN: A randomized,
      prospective, double-blind study. SETTING: A university-affiliated medical center.
      PARTICIPANTS: Twenty patients undergoing lateral thoracotomy for either pulmonary
      wedge resection, lobectomy, or pneumonectomy. INTERVENTION: Nine patients
      received epidural hydromorphone, and 11 patients received intrapleural
      bupivacaine in the postoperative period. MEASUREMENTS AND MAIN RESULTS: Severity
      of pain was assessed using a visual analog pain scale (VAPS) (0 to 100 mm) at 1,
      3, and 5 hours. Patients receiving epidural hydromorphone had a statistically
      significant improvement in VAPS scores. Patients who received intrapleural
      bupivacaine did not achieve a significant reduction in pain scores. Nine of 11
      patients in the intrapleural bupivacaine group had "failed" postoperative
      analgesia as defined by a VAPS greater than 30. Only 3 of 9 patients in the
      continuous epidural hydromorphone group had "failed" analgesia. CONCLUSION:
      Epidural hydromorphone is superior to intrapleural bupivacaine in achieving
      satisfactory pain outcomes during the first 5 hours after thoracotomy.

PMID- 8547555
TI  - Comparison of intrapleural versus intravenous morphine for postthoracotomy pain
      management.
AB  - OBJECTIVE: To compare the analgesic effects of intrapleural and intravenous
      morphine administration for postthoracotomy pain management. DESIGN: Randomized,
      prospective trial. SETTING: University teaching hospital. PARTICIPANTS: Twenty
      eight consenting patients scheduled for elective thoracotomy operations.
      INTERVENTIONS: Patients were randomly allocated into two groups to receive either
      20 mg of intrapleural morphine (IPM group) or 20 mg of intravenous morphine (IVM
      group) at the end of the operation. Plasma morphine levels, arterial pressures,
      heart rate, verbal analog scale (VAS), respiratory rate, and PaCO2 levels were
      compared in two groups. MEASUREMENTS AND MAIN RESULTS: Plasma morphine levels
      were significantly higher in the IVM group at the 5th minute until the 2nd
      postoperative hour. VAS was significantly higher in the IVM group. Respiratory
      rates were significantly higher in the IPM group, whereas PaCO2 remained
      significantly lower than in the IVM group. CONCLUSIONS: IPM achieved better
      analgesia than IVM and this effect is probably attributable to peripheral effects
      of morphine.

PMID- 8547556
TI  - Lidocaine and the inhibition of postoperative pain in coronary artery bypass
      patients.
AB  - OBJECTIVE: This study was designed to evaluate whether a continuous low-dose
      lidocaine infusion reduces postoperative pain and anxiety in patients undergoing
      coronary artery bypass grafting (CABG) and to retrospectively examine time to
      extubation, intensive care unit stay (ICU), and hospital length of stay. DESIGN:
      A double-blinded, randomized, and prospective approach. SETTING: Hospital
      patients undergoing first-time CABG. PARTICIPANTS: After informed consent, 100
      patients were enrolled in this study. INTERVENTIONS: Lidocaine infusion or
      placebo substitute was begun after induction of anesthesia. The
      fentanyl/midazolam infusion was discontinued on ICU admission; lidocaine or
      placebo continued until ICU discharge. Supplemental fentanyl, midazolam, or
      propranolol was administered for pain, anxiety, or hemodynamic stress.
      MEASUREMENTS AND MAIN RESULTS: Drug dosages were compared between groups.
      Postoperative assessment included visual analog pain score, hemodynamics,
      sedation score, and nursing assessment. Mean total dosages of fentanyl,
      midazolam, and propranolol between the lidocaine and placebo groups were 620.40
      +/- 815.74 microgram versus 689.16 +/- 692.99 microgram, p = 0.244; 0.54 +/- 1.13
      mg versus 1.20 +/- 2.44 mg p = 0.465; 0.11 +/- 0.75 mg versus 3.56 +/- 17.2 mg, p
      = 0.564, respectively. Times to extubation, ICU length of stay, and hospital stay
      did not achieve statistical significance. CONCLUSIONS: Continuous infusion of low
      dose lidocaine did not significantly decrease supplemental fentanyl, midazolam,
      or propranolol requirement postoperatively. Similarly, a lidocaine infusion does
      not result in reduced time to extubation. ICU stay, or hospital length of stay.

PMID- 8547557
TI  - Determinants of systolic pressure variation in patients ventilated after vascular
      surgery.
AB  - OBJECTIVE: To discover the predominant determinant of systolic pressure variation
      during positive-pressure ventilation in mechanically ventilated patients after a
      vascular surgical procedure. DESIGN: Case control study. SETTING: Postanesthesia
      care unit at a university hospital. PARTICIPANTS: Eleven patients who were
      sedated during mechanical ventilation after abdominal aortic surgery.
      INTERVENTIONS: Radial arterial pressure and airway pressure were simultaneously
      recorded. The systolic pressure variation was measured as the mean difference
      between the maximal and minimal systolic pressure values during five consecutive
      mechanical breaths. The delta down was measured as the difference between the
      systolic blood pressure during apnea and the minimal values of the systolic
      pressure after one mechanical breath. The velocity time integral, which is
      closely related to stroke volume, was measured throughout the systolic pressure
      measurements. MEASUREMENTS AND MAIN RESULTS: Positive correlation was found
      between changes in velocity time integral and the magnitude of both systolic
      pressure variation (r = 0.73) and delta down (r = 0.80). Volume loading did not
      significantly modify systolic blood pressure. However, it did not significantly
      decrease systolic pressure variation and delta down. The corresponding changes in
      velocity time integral provoked by mechanical ventilation decreased significantly
      as well. CONCLUSIONS: The decrease in systolic pressure provoked by positive
      pressure inspiration reflects simultaneous decreases in stroke volume. This
      suggests that a decrease in left ventricular filling, associated with positive
      pressure inspiration, is responsible for systolic pressure variation. This
      finding confirms the interest in considering systolic pressure variation to
      provide reliable information about the responsiveness of the heart to preload
      variations.

PMID- 8547558
TI  - Closed mitral valvotomy and elective ventilation in the postoperative period:
      effect of mild hypercarbia on right ventricular function.
AB  - OBJECTIVES: It is customary to extubate patients immediately after closed mitral
      valvotomy. These patients often have deranged respiratory function caused by
      chronic lung congestion. The left ventricular function may also be subnormal
      after valvotomy in some patients. Therefore, elective ventilation for some
      duration in the postoperative period can be beneficial to these patients. This
      work is an attempt to find whether elective ventilation should be preferred over
      immediate extubation in these patients. DESIGN: A prospective randomized study.
      SETTING: The study was performed in a tertiary care hospital, and the patients
      are referred from the northern states of India. PARTICIPANTS: One hundred
      patients undergoing elective closed mitral valvotomy were included in the initial
      part of the study. Ten more patients were studied to evaluate the effect of mild
      hypercarbia on right ventricular function after closed mitral valvotomy.
      INTERVENTIONS: One hundred patients were divided into two groups of 50 each.
      Group 1 consisted of patients in whom the neuromuscular blockade was reversed at
      the end of surgery with neostigmine and atropine and the trachea was extubated.
      In group 2, the residual neuromuscular paralysis was not reversed and the
      patients were electively ventilated in the postoperative period for an average
      duration of 5 hours and 29 minutes +/- 1 hour and 58 minutes. In all the patients
      in both the groups, electrocardiogram, direct arterial blood pressure, and oxygen
      saturation were continuously monitored, and arterial blood gases were measured
      intermittently throughout the study period. Because the results showed that there
      was mild hypercarbia, 30 minutes after extubation in group 1, 10 more patients
      were studied to evaluate the effect of mild hypercarbia on right ventricular
      function after surgery. Patients were ventilated after surgery (F1O2 = 1) to
      maintain normocarbia (PaCO238.6 +/- 3.4 mmHg). Mild hypercarbia PaCO251.5 +/- 3.7
      mmHg) followed by normocarbia (PaCO2 40 +/- 2.5 mmHg) was induced by adjusting
      the ventilator rate with a constant tidal volume. Standard hemodynamic
      measurements were performed at each stage. MEASUREMENTS AND MAIN RESULTS:
      Although all the patients maintained satisfactory and stable hemodynamics in the
      postoperative period, the PaCO2 at the end of 30 minutes of extubation was
      significantly higher in group 1 (48.1 +/- 5.3 mmHg) as compared with group 2
      (40.2 +/- 4.3 mmHg, p < 0.001). Mild hypercarbia significantly increased
      pulmonary vascular resistance (p < 0.01), mean pulmonary arterial pressure (p <
      0.001), right ventricular stroke work (p < 0.01), right ventricular systolic
      pressure (p < 0.01), and right ventricular end-diastolic pressure (p < 0.001).
      The effect was not totally reversible with CO2 washout as all parameters except
      right ventricular end-diastolic pressure and pulmonary vascular resistance
      continued to remain significantly higher when normocarbia was restored. The
      significant changes in systemic hemodynamics produced by hypercarbia were
      increases in cardiac index, mean arterial pressure, and pulmonary capillary wedge
      pressure. CONCLUSIONS: Avoidance of even mild hypercarbia, therefore, appears
      advisable in the early postoperative period because of potential impedence to
      right ventricular ejection. Continuous monitoring of end-tidal CO2 and frequent
      blood gas analyses should be practiced, and elective ventilation should be
      considered in patients with long-standing disease and pulmonary hypertension.

PMID- 8547559
TI  - The role of transesophageal echocardiography during the Ross procedure.

PMID- 8547560
TI  - Intraoperative migration of a clamshell device.

PMID- 8547561
TI  - Hypermetabolism during bilateral single-lung transplantation requiring
      cardiopulmonary bypass.

PMID- 8547562
TI  - Avoidance of cardiopulmonary bypass during bilateral sequential lung
      transplantation using inhaled nitric oxide.

PMID- 8547563
TI  - Management of the parturient with severe aortic incompetence.

PMID- 8547564
TI  - High-frequency oscillatory ventilation in the management of infants with
      pulmonary hemorrhage after cardiac surgery.

PMID- 8547565
TI  - Anesthetic considerations for descending thoracic aortic surgery: Part 1.

PMID- 8547566
TI  - Transcranial Doppler ultrasonography: what is its role in cardiac and vascular
      surgical patients?

PMID- 8547567
TI  - Case 4--1995. Intraoperative acute myocardial failure after orthotopic heart
      transplantation.

PMID- 8547568
TI  - Pro: glucose priming solutions should be used for cardiopulmonary bypass.
AB  - Current knowledge suggests that risks of glucose-containing solutions for
      patients undergoing CPB are hypothetical at best. Instead, patients may benefit
      from reduced perioperative fluid requirements bestowed by intraoperative glucose
      containing solutions. This risk-benefit analysis does not apply to patients
      undergoing circulatory arrest. This population endures the certain risk of global
      CNS ischemia; furthermore, no studies address the effect of glucose on fluid
      requirements in this population. As the benefit of glucose during operations
      requiring circulatory arrest is unknown and the probable risk of exacerbating
      global CNS is high, deliberate hyperglycemia in this population is probably
      unwise. For patients undergoing CPB without circulatory arrest, the risk-benefit
      balance falls in favor of adding glucose. The contention that hyperglycemia
      worsens CNS deficits after cardiac operation is undocumented and may not be true.
      For their patients undergoing CPB, clinicians should seriously consider using
      glucose-containing priming solutions.

PMID- 8547569
TI  - Con: glucose priming solutions should not be used for cardiopulmonary bypass.
AB  - In conclusion, the advantage of glucose-containing CPB priming solutions are
      quite modest. In contrast, the weight of current evidence strongly supports the
      notion that hyperglycemia is far more likely to be detrimental than beneficial to
      a brain challenged by ischemia, especially when there is reperfusion (hypotension
      or circulatory arrest) or when the brain is normothermic. Because neurologic
      complications pose such a serious threat to cardiac surgery patients, avoidance
      of hyperglycemia during surgery and CPB seems prudent at this time. Hence, CPB
      priming solutions should not contain glucose.

PMID- 8547571
TI  - Lung separation: a final, final word.

PMID- 8547570
TI  - Sudden cardiovascular collapse on skin closure after routine coronary artery
      bypass grafting.

PMID- 8547572
TI  - Singing the blues.

PMID- 8547573
TI  - Increased PVRI: due to hypoxia?

PMID- 8547574
TI  - Failure of a membrane oxygenation module during cardiopulmonary bypass and its
      implications for the cardiac anesthesiologist.

PMID- 8547575
TI  - Rifampicin and cyclosporine dosing in heart transplant recipients.

PMID- 8547576
TI  - The accuracy of references in the Journal of Cardiothoracic and Vascular
      Anesthesia.

PMID- 8547577
TI  - Graft-induced restoration of function in hereditary cerebellar ataxia.
AB  - Fetal cerebellar cell suspensions, prepared from wild-type (+/+) mice, were
      implanted bilaterally into the cerebellum of Purkinje cell degeneration' (pcd)
      mutant mice, a model of adult-onset recessively inherited cerebellar ataxia, to
      study the functional effects of the grafts on motor coordination and fatigue
      resistance in a rotating rod treadmill paradigm. The viability of transplanted
      Purkinje cells was verified with immunocytochemistry for calbindin-D28k and for
      glutamate receptor 2/3 subunits and with in situ hybridisation histochemistry for
      insulin-like growth factor I mRNA, biochemical markers normally expressed by
      Purkinje cells in the cerebellum. Sham injections of vehicle did not appreciably
      modify the performance of pcd mutants in the rota-rod tests. On the other hand,
      bilateral cerebellar grafts led to a 3.5-fold increase in the time period that
      recipient pcd mice were able to stay on the rotating drum based on the comparison
      of mean scores (of three trials) or a 5.5-fold increase based on the comparison
      of maximum scores (of the three trials). These findings provide evidence for a
      motor enhancement in the pcd mouse model of hereditary cerebellar ataxia
      following intracerebellar transplantation of primordial Purkinje cells.

PMID- 8547578
TI  - Grafts modulate dopamine transporters of the non-lesioned striatum.
AB  - The effect of intraventricular fetal mesencephalic grafts placed in the
      previously 6-hydroxydopamine (6-OHDA) lesioned striatum on the kinetics of
      [3H]dopamine (DA) uptake into striatal synaptosomes prepared from the non
      lesioned (contralateral) striatum was studied in rats. Using WIN 35,065 as
      specific [3H]DA uptake inhibitor, the equilibrium dissociation constant (Km) of
      [3H]DA uptake into synaptosomes of the non-lesioned (contralateral) striatum did
      not differ between grafted and nongrafted controls 7 months after grafting.
      However, the maximal rate of specific [3H]DA uptake (Vmax) was markedly decreased
      in the non-lesioned striatum of grafted animals. This result indicates that fetal
      mesencephalic grafts reduce the [3H]DNA uptake in the non-lesioned
      (contralateral) striatum by reducing the number of functional DA transporters.

PMID- 8547579
TI  - The rat phospholipase C beta 4 gene is expressed at high abundance in cerebellar
      Purkinje cells.
AB  - Inositol phospholipid-specific phospholipase C (PLC) generates two important
      second messengers, inositol triphosphate and diacylglycerol. The recently cloned
      rat PLC beta 4 cDNA is highly homologous to the norpA cDNA of Drosophila
      melanogaster. We have mapped the PLC beta 4 gene expression in rat brain tissue
      sections by in situ hybridization. The PLC beta 4 gene is expressed at high
      abundance in cerebellar Purkinje cells and neurones of the substantia nigra, the
      median geniculate bodies and the thalamic nuclei. PLC beta 4 transcripts are also
      detected in the mammillary nuclei, the neocortex, the habenula and the olfactory
      bulbs. The specific pattern of gene expression we have observed should help to
      clarify the relationships between the PLC beta 4 and various constituents of
      second-messenger systems involved in transduction mechanisms triggered by the
      stimulation of seven transmembrane domain receptors. The strong gene expression
      in Purkinje cells and retinal neurones suggests that PLC beta 4 may be involved
      in the pathogenesis of mouse and human neurological diseases characterized by
      ataxia and retinal degeneration.

PMID- 8547580
TI  - Localization of NO synthase in rat brain by [3H]L-NG-nitro-arginine
      autoradiography.
AB  - Nitric oxide (NO), a free radical gas that acts as a neural messenger, is
      produced from L-arginine by the enzyme nitric oxide synthase (NOS). The present
      study describes the autoradiographic localization throughout rat brain of the
      binding of [3H]L-NG-nitro-arginine ([3H]L-NOARG), a reversible NOS inhibitor, and
      confirms the heterogeneous distribution of the NOS enzyme. [3H]L-NOARG binding
      was enriched in discrete neuronal populations and the distribution observed was
      identical to that previously described for NOS using immunohistochemistry, in
      situ hybridization and NADPH-diaphorase staining. [3H]L-NOARG autoradiography
      should be a useful method for the further characterization and quantification of
      NOS in brain and other tissues.

PMID- 8547581
TI  - Inhibition of hippocampoprefrontal cortex excitatory responses by the
      mesocortical DA system.
AB  - The prefrontal cortex (PFC) receives dopaminergic (DA) afferents from the ventral
      tegmental area (VTA) and excitatory inputs from the hippocampal formation. The
      present electrophysiological experiments performed in anaesthetized rats
      demonstrate that activation of the mesocortical DA system blocked the spontaneous
      activity of PFC neurones and the excitatory responses induced by hippocampal
      stimulation. These data indicate that there is a convergence in the effects of
      hippocampal and DA mesocortical afferents on common PFC neurones. Furthermore, a
      population of PFC neurones responding to hippocampal stimulation could be
      identified as projecting to either the nucleus accumbens and/or the VTA,
      suggesting that the hippocampus exerts an indirect influence on these two
      structures through the PFC.

PMID- 8547582
TI  - Galanin inhibits the vasodilatatory basalocortical cholinergic system in the
      anaesthetized rat.
AB  - In order to test the putative interaction between galanin and the vasodilatatory
      basalocortical cholinergic system, anaesthetized ventilated rats received a
      microinjection into the substantia innominata of 0.9% NaCl, 50 nmol carbachol, 50
      nmol carbachol and 200 ng galanin, or 200 ng galanin. Cerebral blood flow (CBF)
      was measured with [14C]iodoantipyrine by the tissue sampling technique
      immediately following the intracerebral infusions. Under coinjection conditions,
      the flow increases observed after carbachol microinjection in the ipsilateral
      temporal and frontoparietal cortices were found to be significantly reduced (
      37%, p < or = 0.02 and -25%, p < or = 0.05 respectively) compared with carbachol
      stimulated rats. The infusion of galanin by itself had no effect on CBF. These
      results demonstrate that galanin inhibits the vasodilatatory basalocortical
      cholinergic system and thus may possibly influence CBF by indirect mechanisms.

PMID- 8547583
TI  - Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in
      depression.
AB  - Converging evidence points to hypofunction of the left prefrontal cortex in
      depression. Repetitive transcranial magnetic stimulation (rTMS) activates neurons
      near the surface of the brain. We questioned whether daily left prefrontal rTMS
      might improve mood in depressed subjects and report a pilot study of such
      treatment in six highly medication-resistant depressed inpatients. Depression
      scores significantly improved for the group as a whole (Hamilton Depression
      Scores decreased from 23.8 +/- 4.2 (s.d.) at baseline to 17.5 +/- 8.4 after
      treatment; t = 3.03, 5DF, p = 0.02, two-tailed paired t-test). Two subjects
      showed robust mood improvement which occurred progressively over the course of
      several weeks. In one subject, depression symptoms completely remitted for the
      first time in 3 years. Daily left prefrontal rTMS appears to be safe, well
      tolerated and may alleviate depression.

PMID- 8547584
TI  - Leukaemia inhibitory factor prevents injury induced proliferation of striatal
      dopamine uptake sites.
AB  - The injury associated with implantation of an inert gelatin matrix (gel foam)
      into normal mouse striatum induces a long-lived increase in binding of
      [3H]mazindol to presynaptic dopamine uptake sites, probably due to proliferation
      of striatal dopaminergic terminals. Because of the known effects of leukaemia
      inhibitory factor (LIF) on catecholaminergic cells, we tested the hypothesis that
      LIF may alter the striatal dopaminergic response to injury in vivo. Application
      of LIF to mouse striatum in a gel foam implant abolished the usual injury induced
      proliferation of dopamine uptake sites. The ability of LIF to prevent
      proliferation of dopamine terminals may have important implications for our
      understanding of neural regeneration, the aetiology of Parkinson's disease and
      its treatment by intrastriatal grafting.

PMID- 8547585
TI  - Selective impairment of spatial attention during visual search in Alzheimer's
      disease.
AB  - Spatial attention during visual search was examined in 14 persons with mild
      Alzheimer's disease (AD) and 28 healthy older subjects, 14 aged 65-74 (young
      old), and 14 aged 75-85 (old-old). Subjects searched for single feature (color)
      or conjunction (color + letter) targets in displays of 10 or 15 letters. Precues
      of differing sizes were used to provide localizing information of varying
      precision. Effects of display size and cue size on reaction time (RT) for color
      search were similar in AD subjects and controls. For color + letter search,
      however, AD patients showed minimal effects of cue size, pointing to an
      impairment in AD in the spatial focusing of attention during visual search.
      Pathology affecting the association parietal and extrastriate areas may mediate
      impairment of spatial attention and visual search in AD.

PMID- 8547586
TI  - Dissociation of pathways for object and spatial vision: a PET study in humans.
AB  - A positron emission tomography (PET) study was conducted to determine which brain
      regions are differentially involved in visual object identification and object
      localization. Subjects engaged in a spatial task in which they matched the
      location of common objects, and an object task in which they matched the identity
      of common objects. In both tasks the stimulus arrangements used were of the same
      kind. Regional cerebral blood flow data showed that a right-sided region in the
      inferior parietal lobule was more activated during spatial than during object
      matching. In contrast, bilateral occipitotemporal regions, with the left more
      predominant, were more activated during object than spatial matching. These
      results provide support for Ungerleider and Mishkin's dual pathway model of
      vision and indicate important patterns of lateralization in the human visual
      system.

PMID- 8547587
TI  - Calretinin-positive Cajal-Retzius cells persist in the adult human neocortex.
AB  - The occurrence of Cajal-Retzius (CjRe) cells was studied in four cortical areas
      of five normal adult humans using antibodies against calretinin. Calretinin
      immunofluorescence and autofluorescence of lipofusin granules in CjRe cells were
      visualized by dual channel confocal laser scanning microscopy. Three types of
      CjRe cells existed in the adult human cortex: horizontal, triangular and
      multipolar, and their number did not decrease with ageing. Horizontal CjRe cells
      were found in all cortical areas; they contained no lipofusin or less than other
      cells. Triangular CjRe cells with descending dendrites were less numerous.
      Multipolar CjRe cells were rare and contained more lipofuscin. We conclude that
      calretinin-immunoreactivity can be used to study CjRe cell morphology in normal
      and diseased adult human brain.

PMID- 8547588
TI  - beta-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate
      uptake in cultured astrocytes: implications for Alzheimer's disease.
AB  - beta-Amyloid (A beta), the central constituent of senile plaques in Alzheimer's
      disease (AD) brains, was shown by us recently to generate free radicals in an
      oxygen dependent mechanism. A beta-derived free radicals were detected directly
      using electron paramagnetic resonance (EPR) spin trapping techniques employing
      the spin trap phenyl-alpha-tert-butylnitrone (PBN). We have extended these
      studies to investigate the nature of the oxyradicals derived from A beta
      peptides, and we show that these free radicals are able to inhibit glutamate
      uptake in cultured astrocytes. An implication of inhibited astrocyte glutamate
      uptake in brain is increased extracellular levels of glutamate, which is
      excitotoxic to neurons. These results support the hypothesis that A beta
      neurotoxicity in AD may be due in part to A beta-derived, oxygen-dependent free
      radical inhibition of glutamate uptake.

PMID- 8547589
TI  - Functional role of the prefrontal cortex in retrieval of memories: a PET study.
AB  - Retrieval of information from episodic memory involves the processes invoked by
      the attempt to remember (retrieval attempt) as well as processes associated with
      the successful retrieval of stored information (ecphory). Previous PET studies of
      memory have shown an activation of the prefrontal cortex in memory retrieval
      tasks, and we hypothesised that this activation represents retrieval attempt, not
      ecphory. This hypothesis was directly directed using [15O]H2 PET imaging in 19
      healthy subjects who performed three matched tasks which involved different
      levels of retrieval attempt and ecphory. The results showed that retrieval
      attempt was associated with activation of the prefrontal cortex, right greater
      than left, while ecphory involved the posterior cortical regions. These findings
      illuminate the functional role of the different neuroanatomical regions involved
      in episodic remembering.

PMID- 8547590
TI  - MK-801 decreases striatal and cortical GAD65 mRNA levels.
AB  - Levels of mRNAs encoding for the two isoforms of glutamate decarboxylase, GAD67
      and GAD65, were quantified in the rat striatum and cerebral cortex following
      single injections of the non-competitive NMDA receptor antagonist MK-801. Acute
      MK-801 induced a dose-dependent decrease in GAD65 mRNA levels in ventral sectors
      of the dorsal striatum. No statistically significant changes in GAD67 mRNA levels
      were measured in the same conditions. In the frontal and cingulate cortex, GAD65
      but not GAD67 mRNA levels were significantly decreased after a single high dose
      of MK-801 (0.1 mg kg-1). These results suggest that NMDA receptors are involved
      in the transcriptional regulation of the GABA synthesizing enzyme, GAD65.

PMID- 8547591
TI  - NMDA sensitivity is neurite enhanced.
AB  - Glutamate toxicity in retinal ganglion cells has been well documented both in
      vitro and in vitro, and may play a role in both normal neuronal development and a
      variety of pathological states. Glutamate receptors are found on cell bodies and
      neuronal processes, both axons and dendrites. Other work has suggested that one
      or more of these locales may play a more pronounced role in glutamate-mediated
      toxicity. We now report that N-methyl-D-aspartate (NMDA) is more toxic to retinal
      ganglion cells with neurites. Cells without neurites were relatively unaffected
      by glutamate or NMDA. Cells with longer neurites or more neurite branch points
      were more likely to sustain NMDA-mediated neurotoxicity. These observations
      suggest that glutamate-mediated loss may be mediated through NMDA receptors found
      on neurites, rather than through a direct effect on the cell body.

PMID- 8547592
TI  - Dissociation between two modes of spatial processing by a visual form agnosic.
AB  - We report a dissociation between two aspects of visuospatial processing in a
      patient with a profound impairment in the visual perception of objects ('visual
      form agnosia'). The orientation-in-depth of a visual field ('visual pitch') was
      found to systematically influence the elevation at which she perceived her own
      eye level, just as it does in normal individuals; but at the same time, she was
      unable to discriminate perceptually the orientation-in-depth of the same visual
      field, a trivial task for individuals with normal vision. These results suggest
      that, in the normal brain, the processes that integrate orientation information
      from the visual field with extraretinal information about eye position are
      separable from those supporting the perception of the orientation of the visual
      field itself. The pattern of brain damage in D.F., in conjunction with the
      reported dissociation, suggests that the former set of processes maps onto the
      stream of information flowing from primary visual cortex to the posterior
      parietal cortex, the so-called dorsal stream, whereas the latter involves the
      projections from primary visual cortex to the inferotemporal cortex, the so
      called ventral stream.

PMID- 8547593
TI  - Agmatine (decarboxylated arginine) is synthesized and stored in astrocytes.
AB  - We investigated whether astrocytes store and synthesize agmatine (decarboxylated
      arginine), an endogenous ligand for imidazoline and alpha 2-adrenergic receptors,
      in brain. Agmatine, detected chemically and immunocytochemically, is contained in
      cultured astrocytes and C6 glioma cells (8.5 +/- 1.4 and 1.8 +/- 0.6 nmol mg-1
      protein, respectively). Glial membranes express activity for arginine
      decarboxylase (ADC), the biosynthetic enzyme for agmatine (astrocytes 85.4 +/-
      9.2; C6 cells 18.2 +/- 3.12 nmol h-1 mg-1 protein). Lipopolysaccharide, and
      inducer of glial nitric oxide synthase (iNOS), significantly reduced (C6) or did
      not affect (astrocytes) ADC activity. Inferferon-gamma, not affecting iNOS,
      elevated ADC activity in both cell types. Astrocytes are a site of synthesis and
      storage of agmatine. ADC and iNOS enzymes synthesizing distinct bioactive
      products from L-arginine, may be reciprocally regulated.

PMID- 8547594
TI  - Developmental changes in carbachol-stimulated phosphoinositide turnover in
      synaptoneurosomes of the robust nucleus of the archistriatum in the zebra finch.
AB  - The effects of acetylcholine (ACh) on synaptoneurosomes of the robust nucleus of
      the archistriatum (RA), one of the song control nuclei, were investigated during
      the sensitive period of song learning in the zebra finch. Carbachol (an ACh
      agonist) stimulated phosphoinositide (PI) turnover at three different ages.
      Corresponding to a marked increase in ACh levels in the RA, carbachol-stimulated
      PI turnover peaked during the most sensitive learning period in the life of the
      zebra finch. These findings suggest that ACh contributes to the regulation of
      synaptic plasticity in RA neurones involved with song learning in the zebra
      finch.

PMID- 8547595
TI  - Current components stimulated by different G-proteins in Limulus ventral
      photoreceptor.
AB  - The components of the light-activated current in ventral photoreceptor of Limulus
      have different physical and pharmacological properties, indicating the operation
      of different transduction pathways. We investigated whether these pathways are
      activated by different G-proteins. An antiserum, directed against the C-terminal
      sequence QLNLKEYNLV of the alpha subunit of the Gq-protein, which is present in
      squid photoreceptor, was injected into the ventral photoreceptor of Limulus. This
      Gq-alpha mediates the light-dependent activation of PLC. Injections of the
      antibody into the photoreceptor blocked the second component of the light-evoked
      current in Limulus ventral photoreceptor, but the other components could still be
      activated. The results support our earlier hypothesis that the transduction
      pathways of the current components are selectively activated by different G
      proteins.

PMID- 8547596
TI  - Ischemia-induced changes in extracellular levels of striatal cyclic GMP: role of
      nitric oxide.
AB  - Using microdialysis, we evaluated temporal changes in striatal extracellular cGMP
      level following ischemia and its relationship to nitric oxide (NO) production. In
      untreated animals, significant elevation of cGMP was observed during ischemia and
      during 4 h of recirculation. In animals treated with L-NAME ischemia induced a
      modest increase in the cGMP level, but this level was significantly lower than
      that observed in the untreated animals. These results demonstrate first, that the
      microdialysis technique can be used to detect changes in extracellular cGMP
      levels during ischemia and second, that ischemia and recirculation induce a rise
      in cGMP which is diminished by nitric oxide synthase inhibition, suggesting a
      linkage to NO production.

PMID- 8547597
TI  - Evoked brain potentials and memory: more positivity in response to forgotten
      items.
AB  - Brain evoked potentials (EPs) were recorded in human subjects participating in a
      free recall memory task involving retroactive interference. A learning list was
      presented five times. The fifth repetition was followed by an interference list.
      Both lists were composed of either words or abstract figures, and each subject
      experienced each of four possible combinations. Analysis of items recalled during
      the learning phase revealed larger N400 and P600 amplitudes for those items that
      were later forgotten vs remembered following the interference. This contradicts
      the usual finding that more positivity is associated with better memory. However,
      both the present as well as the extant findings can be explained in terms of
      cognitive resource allocation. Specifically, items receiving greater allocations
      are more likely to be immediately recalled. However, as the number of items in
      working memory increases, the allocation required to add new items also
      increases. Thus, items learned on later trials would receive larger allocations
      (i.e., larger positivities) than items learned earlier, yet would be more likely
      forgotten following the interference because their presence in memory would not
      be reinforced during later trials, as is the case with items learned earlier.

PMID- 8547599
TI  - Distribution of neurone-specific clathrin light chain b between clathrin-coated
      vesicle subclasses.
AB  - The clathrin light chains (LCs) may serve to introduce diversity into the
      structure and/or function of clathrin-coated vesicles (CVs). To understand such
      involvement of LCs, it is advantageous to study the distribution of various LC
      subclasses among CV populations with specified structure and/or function. We have
      previously separated three populations of CV from rat brain, the small- and
      medium-sized populations originated from neurones and large-sized one from glial
      cells. In the present study, we examined whether the neurone-specific LCb is
      localized in either or both of those neuronal CV populations by immunogold
      electron microscopy, and showed the distribution of the LCb between both CVs.
      These findings suggest that the neurone-specific LC subclass does not specify
      morphologically distinct subtype of neuronal CVs but plays a role in constructing
      the CVs generally smaller than those from other tissues and/or in neurone
      specific mechanisms associated with both of the neuronal CVs.

PMID- 8547598
TI  - Function and expression of the Bcl-x gene in the developing and adult nervous
      system.
AB  - We have shown that overexpression of Bcl-x can rescue sympathetic neurones from
      nerve growth factor deprivation in vitro. We have also examined the distribution
      and expression of Bcl-x mRNA in the developing and adult nervous system using
      Northern blot and in situ hybridization. Bcl-x mRNA is widespread during
      development of the nervous system. In embryonic spinal cord, mRNA levels increase
      at the beginning of the naturally occurring cell death period, suggesting that
      Bcl-x may be involved in the selection of neurones during this period. In the
      brain, Bcl-x expression increases after birth to reach a high level in the adult
      brain. Neurones from the cortex, olfactory bulb, and Purkinje cells are among
      those expressing the highest levels of Bcl-x mRNA. The widespread expression of
      Bcl-x during development and in adult brain suggests of a role for Bcl-x beyond
      simply protecting neurones from developmental cell death.

PMID- 8547600
TI  - Neuroactive steroids modulate GABA inhibition of hypothalamic somatostatin
      release.
AB  - The reduced steroids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone)
      and 3 alpha,21-di-hydroxy-5 alpha-pregnan-20-one (allotetrahydroDOC) are potent
      ligands of GABAA receptors. This study examined the possible modulatory effect of
      these metabolites on GABA inhibition of somatostatin release in cultured
      hypothalamic neurones. Allopregnanolone potentiates GABA inhibition, and reversed
      picrotoxin and bicuculline-induced augmentation of somatostatin release in a dose
      dependent manner. AllotetrahydroDOC also inhibits the stimulated release induced
      by the antagonists, but did not modify that induced by depolarizing
      concentrations of K+. Pregnenolone sulphate had no effect on picrotoxin-induced
      somatostatin release. These findings clearly establish that 3 alpha
      hydroxysteroids modulate GABA inhibition of hypothalamic somatostatin release.

PMID- 8547601
TI  - Effects of nocodazole and taxol on glycine evoked currents on rat spinal cord
      neurones in culture.
AB  - We examined the effect of altering the cytoskeleton polymerization state by
      treatment with nocodazole and taxol on glycine-evoked currents in patch-clamp
      recordings from cultured spinal cord neurones. Adding ATP and GTP to the pipette
      solution did not prevent the rundown of the peak current. In the absence or in
      the presence of ATP, the proportion of the non-desensitizing part of the glycine
      evoked-current declined with time. Adding intracellular GTP and ATP stabilized
      glycine-evoked responses although the proportion of non-inactivating current was
      reduced. Nocodazole reduced by itself the proportion of the non-inactivating
      current whereas taxol (with ATP and GTP) had an opposite effect. These results
      suggest that the polymerization state of microtubules has functional consequences
      on glycine receptors.

PMID- 8547602
TI  - Protective effects of brain-derived neurotrophic factor on the development of
      hippocampal kindling in the rat.
AB  - Recent data have suggested the involvement of neurotrophins in the cascade of
      events occurring during seizure development. In particular, expression of both
      brain-derived neurotrophic factor (BDNF) and its receptor mRNAs increases in
      different brain structures after convulsive seizures. The physiological
      significance of this increase was investigated by chronic intrahippocampal
      perfusion of BDNF in the model of dorsal hippocampal kindling in the rat. A 7 day
      perfusion of BDNF, in the region of the stimulating electrode, blocked the
      development of kindling during the perfusion period and for the following 15
      days. These results provide in vivo evidence for a protective role of BDNF in the
      regulation of plasticity involved in epileptogenesis in adult brain.

PMID- 8547604
TI  - Modulation of the rat suprachiasmatic circadian clock by melatonin in vitro.
AB  - The pineal hormone melatonin regulates daily and seasonal rhythms, at least in
      part through an action on the mammalian biological clock in the suprachiasmatic
      nuclei (SCN). Melatonin was tested in vitro (10(-15)-10(-6) M; ZT9.5-10.5) for
      its effect on the circadian peak in neuronal firing rate in the rat SCN slice. It
      produced a concentration-related phase advance (maximum advance = 3 +/- 0.3 h at
      10(-9) M, n = 3; minimum effective concentration = 10(-13) M; EC50 = 1.2 x 10(
      12) M). The melatonin receptor antagonist luzindole (10(-5) M) blocked the phase
      advance produced by melatonin (10(-9) M), whilst having no effect on its own.
      These data show that the effect of melatonin on the SCN clock, measured via the
      circadian rhythm of neuronal firing rate in the nuclei, is consistent with a
      concentration-dependent action via a high affinity melatonin receptor.

PMID- 8547603
TI  - Widespread but cell type-specific expression of the mouse neurofibromatosis type
      2 gene.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disease in which loss of
      function mutations of the NF2 gene lead to the development of schwannomas,
      meningiomas and juvenile cataracts. We studied the mouse NF2 homologue (Nf2) to
      determine its precise pattern of mRNA and protein expression. In situ
      hybridization showed that Nf2 is expressed in neuronal cells as well as in
      epithelial and fibre cells of the lens. The Nf2 protein, schwannomin, is
      expressed as a single protein isoform of approximately 80 kDa in neuronal and non
      neuronal tissues. In Purkinje cells of the cerebellum and motor neurones of the
      spinal cord, the protein is in the cytoplasm. In non-neuronal tissues
      immunostaining showed expression in cells of the tunica intima of blood vessels.
      We conclude that there is a widespread but cell type-specific expression of
      schwannomin.

PMID- 8547605
TI  - Band 4.2 Komatsu: 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene
      associated with total deficiency of band 4.2, hemolytic anemia with
      ovalostomatocytosis and marked disruption of the cytoskeletal network.
AB  - A novel mutation of 523 GAT-->TAT (175 Asp-->Tyr) in exon 4 of the band 4.2 gene
      was detected in a 37-year-old Japanese patient with total lack of band 4.2
      protein, designated as allele 4.2 Komatsu. In this patient, moderate
      uncompensated hemolytic anemia (red cell count 3.38 x 10(6)/microliters,
      hemoglobin 10.8 g/dl, hematocrit 30.9%, reticulocytes 12.4%, indirect bilirubin
      1.84 mg/dl) with ovalostomatocytosis and increased osmotic fragility had been
      noted since birth. Family studies revealed no overt hemolytic anemia in other
      family members, essentially normal red cell morphology, and a normal profile of
      red cell membrane proteins including band 4.2. Genetic studies proved that the
      proband was homozygous and all the family members studied were heterozygous with
      respect to the mutation of 523 GAT-->TAT of the band 4.2 gene. Although band 4.2
      was completely absent in the proband, trace amounts of 72 kDa and 74 kDa peptides
      were detected in the red cells of all the family members, in which the mutation
      of 424 GCT-->ACT at exon 3 of the band 4.2 gene (Nippon type) was not present.
      Electron microscopic studies with the surface replica method and the quick-freeze
      deep-etching method showed the most marked disorganization of the cytoskeletal
      network in the patient's red cells in situ among the cases of band 4.2
      deficiencies we have studied. This suggests that the amino acid of the band 4.2
      protein, which was affected by the present mutation in exon 4, is much more
      crucial for the functioning of band 4.2 protein than that at codon 142 in exon 3.
      The cytoplasmic domain of band 3 in the proband's red cells was essentially
      normal in protein chemistry and in gene analysis with single-stranded
      conformation polymorphism (SSCP).

PMID- 8547606
TI  - A new phenotypic classification of bone marrow plasmacytosis.
AB  - Here, we propose a new phenotypic classification of bone marrow plasmacytosis. By
      2-color phenotypic analysis with FITC anti-CD38 and PE anti-CD19, -CD56, -VLA-5
      or MPC-1 antibody, plasma cells are easily identified on the histogram, even
      though no more than 1% of plasma cells are found in the bone marrow. Hence,
      plasma cells are phenotypically classified into polyclonal (reactive) (CD19+CD56
      ) or monoclonal (neoplastic) plasma cells (mostly CD19-CD56+), and furthermore
      immature (VLA-5-MPC-1-), intermediate (VLA-5-MPC-1+) and mature plasma cells (VLA
      5+MPC-1+). According to these findings, plasmacytosis in the bone marrow can be
      classified into polyclonal marrow plasmacytosis (POMP) and monoclonal marrow
      plasmacytosis (MOMP) states. The MOMP state is further subclassified into MOMP-1
      and MOMP-2, MOMP-3 and MOMP-4; MOMP-1 is defined by co-existence of monoclonal
      plasma cells and polyclonal plasma cells, and MOMP-2 to MOMP-4 are dependent on
      increased proportions of VLA-5-MPC-1- immature myeloma (plasma) cells. We found
      that the cases of benign monoclonal gammopathy (BMG) according to the
      conventional classification were in the MOMP-1 state, and myelomas could be
      classified into the MOMP-2 to MOMP-4 state. Subclassification of the MOMP state
      may be useful in determining the prognosis of myelomas, where an increase in
      immature myeloma cells is reported to correlate well with their aggravation
      during the clinical courses. Therefore, this new phenotypic classification of
      bone marrow plasmacytosis (POMP and MOMP-1 to MOMP-4) will contribute to
      differential diagnosis and understanding of therapeutic responses and prognosis
      in myelomas.

PMID- 8547607
TI  - Shear stress-induced platelet aggregation in various types of von Willebrand
      disease.
AB  - We here examined the shear stress-induced platelet aggregation (SIPA) in various
      types of von Willebrand Disease (vWD), using a novel cone-and-plate viscometer
      recently developed by Ikeda et al. [1]. Under experimental conditions of high
      shear stress (90-108 dyne/cm2) known to induce von Willebrand factor (vWF)
      dependent platelet aggregation in normal individuals, a variety of SIPA patterns,
      from a normal to total defect, were observed in 6 patients with type I vWD, while
      SIPA was totally absent in all 7 type IIA patients examined. One patient with
      Normandy type vWD exhibited a normal SIPA pattern under these experimental
      conditions. These findings, together with the vWF parameters of each patient,
      suggested that the presence of higher molecular weight multimers of plasma vWF,
      as well as an appropriate level of vWF antigen, is essential for SIPA to occur
      under high shear stress. Interestingly, vWF-dependent SIPA in 3 patients with
      type IIB vWD was found to be initiated by a low shear stress force, which did not
      induce such platelet aggregation in normal individuals. This might explain the
      intravessel platelet clumping that occurs, resulting in the intermittent
      thrombocytopenia observed in this type of the disease.

PMID- 8547608
TI  - Identification of the antithrombin III Kyoto mutation by restriction fragment
      length polymorphism analysis.
AB  - Clarification of the molecular biologic abnormality underlying antithrombin III
      (AT III) deficiency is important to a complete understanding of the coagulation
      system. We have reported previously the deficiency of AT III Kyoto in which there
      has been a single substitution of thymine for guanine at codon 406 of exon VI.
      This results in the amino acid substitution of methionine for arginine. The
      nucleotide substitution at codon 406 in the mutant allele eliminates a Hae III
      restriction site. Accordingly, Hae III restriction analysis of the PCR fragments
      in this family could segregate the deficient members from the normal members,
      enabling the detection of the existence of Hae III restriction fragment length
      polymorphism of the PCR product (PCR-RFLP). Moreover, we confirmed by direct DNA
      sequencing with the polymerase chain reaction that the tested deficient members
      in an AT III Kyoto family inherit the same type of mutation in their genes. In
      conclusion, Hae III PCR-RFLP can be a useful method for screening of this mutant
      gene in the family.

PMID- 8547609
TI  - Double mutations of the N-ras gene in a patient with acute myelomonocytic
      leukemia.
AB  - We report a patient with acute myelomonocytic leukemia (AMMoL) who showed two
      independent point mutations of the N-ras gene at codons 12 and 13. Longitudinal
      analysis revealed that one mutation at codon 13 was detectable throughout his
      disease course and the other at codon 12 emerged as a second mutation 14 months
      after the diagnosis was made, at the refractory stage. Cloning to vector and
      subsequent sequencing confirmed that these mutations occurred in different
      alleles. Chromosome findings showed a simple abnormal karyotype at presentation
      and further karyotypic aberrations during his disease course, concomitantly with
      the second mutation of the N-ras gene. These findings revealed a close
      relationship among the disease progression, karyotypic evolution and a newly
      appearing N-ras mutation.

PMID- 8547610
TI  - Synchronous presentation of Epstein-Barr virus-associated Hodgkin's disease and
      adult T-cell leukemia/lymphoma (ATLL) in a patient from an endemic area of ATLL.
AB  - We report a patient from an endemic area of adult T-cell leukemia/lymphoma
      (ATLL), who developed lymphoma with features characteristic of Hodgkin's disease
      (HD). Large atypical Reed-Sternberg/Hodgkin's cells (RS/H cells) had a CD3
      CD15+CD20-CD30+CD45RO- immunophenotype. Epstein-Barr virus (EBV) latent membrane
      protein and EBV-encoded small RNA were detected in the RS/H cells. The patient
      received C-MOPP/ABVD chemotherapy for the HD resulting in a partial response.
      However, relapse occurred and he died of disease progression associated with
      serious bacterial infection. Although serial lymph node biopsies revealed
      consistent presence of the EBV-positive RS/H cells, the background small
      lymphocytes showed progressive increase in pleomorphism and nuclear irregularity.
      The lymphocytes had the T-cell phenotype, CD3+CD4+CD7-CD8-. Southern blot
      analysis using DNA probes for the human T-cell lymphotrophic virus-I (HTLV-I) and
      the T-cell receptor beta-chain gene demonstrated expansion of the HTLV-I infected
      monoclonal T-cells with the disease progression. We concluded that the patient
      synchronously presented two independent lymphoproliferative disorders; EBV
      associated HD and ATLL resulting from HTLV-I infection.

PMID- 8547611
TI  - Migration to an inflammatory site in vivo of paroxysmal nocturnal hemoglobinuria
      lymphocytes.

PMID- 8547612
TI  - Experiences in BMT. Bone Marrow Transplant.

PMID- 8547613
TI  - Tetrasomy of Philadelphia chromosome in myeloblastic crisis of chronic
      myelogenous leukemia.

PMID- 8547614
TI  - [Alban Kohler (1874-1947). Assessment of a clinical radiology pioneer from the
      present-day viewpoint].

PMID- 8547615
TI  - [Detection of breast carcinoma: a statistical-epidemiological study of the
      current situation].
AB  - PURPOSE: Within the framework of the discussed introduction of mammography for
      breast cancer screening in Germany, we were interested in the actual status of
      breast cancer detection. PATIENTS AND METHOD: From 1990-1994, 1019 breast cancer
      patients with 1050 carcinomas were inquired during primary anamnesis whether the
      suspicious finding was first discovered by themselves, their physician at routine
      examination or in routine mammography. RESULTS: In 71.14% of the cases, breast
      changes were first recognised by the patient, in 12.48% palpated by the physician
      and 16.38% were first seen at routine mammography. Cancers discovered by
      physicians or mammography were in statistically significant lower tumour and
      lymph node stages than those found by the patient and could more often be treated
      by breast-conserving regimes. CONCLUSION: However, most breast cancers are still
      first discovered by the patient and are diagnosed at higher stages than those
      discovered by clinical examination or mammography.

PMID- 8547616
TI  - [Castleman's disease: evaluation of 338 cases].
AB  - PURPOSE: To evaluate a large group of patients with Castleman's tumours
      (Castleman's disease = MC) with regard to age, sex and tumour localisation.
      PATIENTS AND METHODS: 338 cases of MC were evaluated. All cases were registered
      by the Lymphknotenregister of the German Society of Pathology, Kiel. RESULTS: 292
      MC of the hyaline vascular type (MC-HV) and 46 of the plasma cell type (MC-PC)
      were found, 259 (76.6%) in nodal and 79 (23.4%) in extranodal localisation. Main
      nodal localisation were the neck (25.5%) and the axilla (12.8%). The mediastinum
      was involved in only 6.2%. There was a slight preference of female (56%) compared
      to male (44%). Patients with MC-PC (mean age: 50 +/- 16.9 years) were
      significantly older (p < 0.001) than patients with MC-HV (mean age: 39 +/- 18.9
      years). CONCLUSIONS: The main localisation of MC is the neck. MC-HV is more
      common than MC-PC. There is a slight preference for women. Mean age of patients
      with MC-PC is approximate 10 years higher than for MC-HV.

PMID- 8547617
TI  - [Value of computed tomography in the diagnosis of fistulas].
AB  - PURPOSE: The purpose of the study was to determine the value of computed
      tomography (CT) in demonstrating fistulae in comparison with conventional
      radiographic methods. METHODS: In a prospective study 25 patients were evaluated
      by conventional radiographic methods and CT. RESULTS: The identification of the
      fistulous tract was possible with CT in 27 of 29 cases, whereas 2 fistulae could
      only be detected by indirect signs. Furthermore, CT showed a larger extent of the
      fistulous tract in 5 patients and revealed complications such as inflammatory
      mass, abscess or osteomyelitis in 11 cases. CONCLUSION: CT seems to be superior
      in demonstrating the extent of a fistulous tract and provides valuable
      information on the surrounding structures.

PMID- 8547618
TI  - [Possibilities of the use of MR tomography-based cerebral blood volume maps in
      the diagnosis of brain tumors].
AB  - PURPOSE: Today contrast enhanced MR imaging is a reliable method for detecting
      mostly distinguishing between different histological types of tumours. In this
      study we use a MR-based method to measure the regional cerebral blood volume
      (rCBV). Using this technique we try to judge the grading and vitality of the
      tumours. METHODS: 26 patients with various types of brain tumours were examined.
      To calculate rCBV-maps of one slice, low-dosed Gd-DTPA was injected as a bolus.
      Using the relaxation effect the obtained signal intensity-time curves were
      converted pixel-wise into rCBV images. For the tumours rCBV-ratios were
      calculated relative to the corresponding area in the contralateral hemisphere.
      RESULTS: In the investigated group all tumours were detected on the basis of a
      raised rCBV-ratio. Since only vital parts of the tumour are perfused, the rCBV
      maps may be used to determine the place of biopsy. CONCLUSIONS: The differential
      diagnosis of all histological tumour types was not possible on the basis of rCBV
      values. Distinction between low grade and high grade gliomas was also not
      significant. However, a low grade glioma can be excluded if the morphological
      images definitely indicate an astrocytoma and if the rCBV-ratio was higher than
      2.

PMID- 8547619
TI  - [Distribution of hematopoietic and fatty bone marrow in the proximal humerus and
      scapula: magnetic resonance tomography and macroscopic anatomy].
AB  - PURPOSE: To establish the distribution pattern of haematopoietic and fatty bone
      marrow on MRI of the proximal humerus and the scapula in correlation with age,
      gender and nutritive factors. MATERIAL AND METHODS: 32 shoulder MR examinations
      (T1-weighted spin-echo and opposed-phase gradient-echo sequences) from 24
      patients and 8 volunteers were analysed retrospectively. The amount of
      haematopoietic bone marrow within the proximal humerus and scapula was classified
      into four groups and was correlated with age (H-test), gender (chi 2-Test), and
      thickness of subcutaneous fat (H-test). The marrow distribution within 10
      scapulae of cadavers over 60 years of age at death was studied. RESULTS: With
      increasing age, the amount of haematopoietic bone marrow in the proximal humeral
      metaphysis tends to decrease from lateral towards medial (H-test, p = 0.3).
      Diaphysis and epiphysis did not show haematopoietic marrow. The amount of
      haematopoietic bone marrow within the paraglenoid region of the scapula also
      revealed a decrease with increasing age (H-test, p = 0.003). Females had higher
      amounts of haematopoietic marrow than males (chi 2-test, p = 0.03). The thickness
      of subcutaneous fat was independent of the marrow distribution. CONCLUSION: The
      amount of haematopoietic bone-marrow of the shoulder girdle decreases with
      increasing age. The knowledge of marrow distribution patterns based upon these
      changes is important for shoulder MRI interpretation to prevent confusion with
      infiltrative disease.

PMID- 8547620
TI  - [Value of Turbo-FLAIR sequence in the diagnosis of brain diseases at 0.5 tesla].
AB  - PURPOSE: Aim of the study was to evaluate FLAIR combined with Turbo-Spin-Echo
      (Turbo-FLAIR) at 0.5 tesla in comparison to conventional T1- and T2-weighted spin
      echo images (SE) in MRI of the brain. MATERIAL AND METHODS: A Turbo-FLAIR
      sequence was optimised for 0.5 Tesla (Philips Gyroscan T5-II) that provided
      seventeen 5 mm sections in 4:21 minutes (TR = 6075 ms, T1 = 1600 ms, TE = 120 ms
      and a turbofactor = 17). Images were compared with T1- (TR = 500 ms, TE = 15 ms)
      proton density and T2-weighted spin-echo (TR = 2500 ms, TE = 20/90 ms) studies in
      10 healthy volunteers and 30 patients with various brain pathologies. RESULTS:
      Turbo-FLAIR could effectively eliminate the CSF signal in all studies except
      ventricular areas with CSF inflow. Contrast-to-noise ratios (C/N) for the
      contrast between lesions and CSF was superior in Turbo-FLAIR. C/N between lesions
      and grey matter was significantly higher in Turbo-FLAIR than in proton density
      (PD)-weighted SE. C/N between lesions and white matter was equal to PD-weighted
      SE but significantly smaller than on T2-weighted SE. Visual analysis showed
      greater lesions conspicuity with Turbo-FLAIR and a higher frequency of detection
      of cortical and subcortical lesions. CONCLUSIONS: Turbo-FLAIR is a reliable and
      practical technique on 0.5 Tesla, that is more sensitive than SE sequences
      especially for the detection of cortical, subcortical lesions and lesions
      surrounded by CSF.

PMID- 8547621
TI  - [MR-guided laser-induced thermotherapy in tumors of the head and neck region:
      initial clinical results].
AB  - PURPOSE: To analyse the value of MR-guided laser-induced thermotherapy (LITT) for
      palliative treatment of recurrent tumours of the head and neck region. MATERIAL
      AND METHODS: 8 patients with recurrent tumours of the head and neck region
      (squamous cell carcinomas n = 6, pleomorphic adenomas n = 2) underwent MR
      controlled LITT. A 7 French laser applicator was inserted under local anaesthesia
      into the centre of the recurrent tumour. A Nd:YAG laser with a wavelength of 1064
      nm was used. Therapy was monitored on-line using special MR thermosequences.
      RESULTS: Preinterventional contrast-enhanced MRI revealed a recurrent tumour of
      the head and neck region for all eight patients. All patients tolerated the
      procedures well under local anaesthesia, with no clinically relevant side
      effects. The MR thermosequences depicted up to 15 mm diameter areas of less
      signal near the laser tip. Postinterventional contrast-enhanced MRI revealed
      hypovascularized areas due to the resulting coagulative necrosis. Coagulative
      necrosis of 4 cc to 28 cc occurred in all patients, and a reduction of clinical
      symptoms was achieved in five. CONCLUSION: The results obtained indicate that
      minimal invasive LITT can be a therapeutic alternative for palliative treatment
      of head and neck tumours.

PMID- 8547622
TI  - [Intraarterial digital subtraction angiography (i.a. DSA) of the lower limb using
      fine needle technique].
AB  - PURPOSE: Severe peripheral arterial occlusive disease (pAOD) requires adequate
      diagnostic imagery of poststenotic and postocclusive vascular regions. This study
      was designed to evaluate the validity of i.a. DSA using fine-needle technique
      (FNA) especially concerning the vascular area of the lower limb. MATERIAL AND
      METHODS: 206 FNA of the lower limb wer evaluated retrospectively. Besides
      evaluation of the image quality of the 1119 angiographic image series, main
      points of interest were the determination of accuracy of the FNA in comparison to
      the operative findings, the average radiocontrast agent consumption and the rate
      of complication. RESULTS: In all cases the image quality was rated either very
      good or good in the pelvic, femoral and popliteal vessels. 94% of the image
      series of the lower leg and foot could be rated as well as very good/good
      although 75% of all patients demonstrated an advanced stage of pAOD. Accuracy of
      FNA compared to operative findings came up to 82%. The average radiocontrast
      consumption amounted to 69 ml per examination. Overall, two major complications
      were seen. CONCLUSION: I.a. DSA of the lower limb using fine-needle-technique is
      an easily applied angiographic method of low radiocontrast agent consumption and
      a low complication rate. Essential information can be acquired preoperatively in
      planning far peripheral bypass anastomoses. Postoperative vascular complications
      can be safely assessed.

PMID- 8547623
TI  - [Temporary cava filter: effective prophylaxis of pulmonary embolism in venous
      thrombosis in the region of the pelvic vascular system and the inferior vena
      cava?].
AB  - PURPOSE: To assess the temporary Gunther filter system concerning handling,
      complication rate and efficacy in respect to prophylaxis of pulmonary embolism.
      PATIENTS AND METHODS: 45 temporary Gunther filters were placed in 44 patients
      (mean age 46 years) with deep venous thrombosis of the iliac and/or inferior vena
      cava. RESULTS: The mean time until filter retrieval was 6.1 +/- 4.1 days (maximum
      14 days) dependent on the success of either thrombolytic therapy or thrombus
      consolidation. 27 patients underwent systemic thrombolytic therapy (61%), three
      patients (7%) received local thrombolysis. 14 patients (32%) were treated with
      heparin in a therapeutic dosage (PTT > 60 sec). We observed four complications
      (8.8%): one accidental arterial puncture (carotid artery on attempting an
      internal jugular vein approach), one infection located at the puncture site and
      one caval vein thrombosis in a patient with known heparin-associated
      thrombocytopenia. One patient died of pulmonary embolism despite correct filter
      positioning. CONCLUSION: Percutaneous placement of inferior vena cava filters is
      therefore an easy, safe and effective prophylaxis in respect of pulmonary
      embolism if combined with thrombolytic therapy or therapeutic heparinisation.

PMID- 8547625
TI  - Sarcoma botryoides in CT imaging. Case report.

PMID- 8547624
TI  - [Percutaneous drainage of refractory necrotizing tumors: experience in 9
      patients].
AB  - PURPOSE: The ranking of percutaneous drainage treatment in necrolytic advanced
      tumours was assessed. METHOD: 9 patients with refractory symptomatic necrolytic
      tumours were treated for alleviation by percutaneous drainage. Additionally, an
      attempt to sclerose the necrotic cavity was performed in 6 patients (6 x
      mitoxantrone 30 mg/24 hrs, of which 1 x additionally 98% alcohol). RESULTS: In 5
      of the 9 patients symptomatic relief was obtained, but complete sclerosing of the
      necrotic cavity succeeded in only two patients. In two patients with necrotic
      tumours of the pelvis there was a bacterial superinfection of the tumour
      necrosis. CONCLUSION: Percutaneous alleviation is only occasionally successful in
      patients with necrolytic tumours. Therapy becomes effective probably only in case
      of successful sclerosing of the tumorous cavity.

PMID- 8547626
TI  - [Imaging of basilar thrombosis with 3D spiral CT angiography].

PMID- 8547627
TI  - [Growth disorders after radiotherapy of Hodgkin's disease in childhood].

PMID- 8547628
TI  - [Intrathoracic splenosis: a rare differential diagnosis of pleural space
      occupying growth].

PMID- 8547629
TI  - [Tracheal rupture after blunt thoracic trauma].

PMID- 8547630
TI  - CD34: structure, biology, and clinical utility.

PMID- 8547631
TI  - Opposing effects of the basic helix-loop-helix transcription factor SCL on
      erythroid and monocytic differentiation.
AB  - The SCL gene (also called Tal-1 or TCL5) was identified because of its
      association with chromosomal translocations in childhood T-cell lymphoid
      leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor that can function
      as a transcriptional activator or repressor. In the adult, SCL expression is
      restricted to hematopoietic cells and tissues, but its function in the process of
      lineage commitment is unknown. The present study was designed to address the role
      of SCL in hematopoietic cell differentiation. SCL expression was determined in
      primary hematopoietic cells through the screening of cDNA samples obtained by
      reverse transcription-polymerase chain reaction (RT-PCR) from single cells at
      different stages of differentiation. SCL RNA expression was highest in
      bipotential and committed erythroid precursors and diminished with subsequent
      maturation to proerythroblasts and normoblasts. In contrast, SCL mRNA was low to
      undetectable in precursors of granulocytes and monocytes and their maturing
      progeny. The same pattern of expression was observed after erythroid or monocytic
      differentiation of a bipotent cell line, TF-1, in that SCL mRNA levels remained
      elevated during erythroid differentiation and were downregulated with monocytic
      differentiation. Accordingly, TF-1 was chosen as a model to investigate the
      functional significance of this divergent pattern of SCL expression in the two
      lineages. Four independent clones stably transfected with an SCL expression
      vector exhibited enhanced spontaneous and delta-aminolevulinic acid-induced
      erythroid differentiation as measured by glycophorin expression and
      hemoglobinization, consistent with the view that SCL is a positive regulator of
      erythroid differentiation. Furthermore, constitutive SCL expression interfered
      with monocytic differentiation, as assessed by the generation of adherent cells
      and the expression of Fc gamma RII in response to TPA. These results suggest that
      the downregulation of SCL may be required for monocytic differentiation.

PMID- 8547632
TI  - Mutational analysis of the alpha subunit of the human interleukin-3 receptor.
AB  - The alpha subunit of the human interleukin-3 receptor (IL-3R alpha) is a 70-kD
      glycoprotein member of the hematopoietin receptor superfamily. This protein
      associates with a beta subunit common to the receptors for IL-5 and granulocyte
      macrophage colony-stimulating factor (GM-CSF) to form a high-affinity receptor
      for IL-3. To identify regions of IL-3R alpha critical for ligand binding and
      receptor function, cDNAs encoding mutant receptors were generated and expressed
      in COS cells along with the beta subunit. Mutant receptors lacking almost the
      entire cytoplasmic domain of IL-3R alpha [IL-3R alpha(CD)] or carrying a
      substitution of trp for leu in the membrane proximal leu-ser-x-trp-ser (LSXWS)
      box bound 125I-IL-3 with nearly the same affinity as wild-type IL-3R alpha. In
      contrast, a mutant lacking the entire "LSXWS" motif failed to bind 125I-IL-3 with
      high affinity despite showing surface expression. In addition, hybrid receptors
      composed of the first 104 amino acids (aa) of IL-3R alpha joined to aa 118
      through 400 of the alpha subunit of the GM-CSF receptor (GM-R alpha) [IL-3R
      alpha/GM-R alpha] or the first 118 aa of GM-R alpha joined to aa 104 through 378
      of IL-3R alpha [GM-R alpha/IL-3R alpha] failed to bind 125I-IL-3 in the presence
      of the beta subunit. A third hybrid receptor composed of the first 281 residues
      of IL-3R alpha fused to residues 306 through 379 of GM-R alpha [IL-3R alpha/GM-R
      alpha-DS] also failed to bind 125I-IL-3 in the presence of the beta subunit but,
      in contrast to the IL-3R alpha/GM-R alpha hybrid, demonstrated weak surface
      expression. Mutant receptors lacking the N-terminal 30 aa and the N-terminal 9 aa
      also did not bind 125I-IL-3 with high affinity, although both were expressed on
      the cell surface. These data suggest that although the cytoplasmic domain and the
      leucine residue of the "LSXWS" box are not critical for ligand binding or beta
      subunit association, the "LSXWS" motif and amino-terminal sequences are important
      for these functions.

PMID- 8547633
TI  - Inhibition of protein kinase C suppresses megakaryocytic differentiation and
      stimulates erythroid differentiation in HEL cells.
AB  - The bisindolylmaleimide, GF109203X (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3
      (1H-indol-3-yl)-maleimide ), a highly selective inhibitor of protein kinase C
      (PKC), was used to test the role of this enzyme in phorbol ester-induced
      megakaryocytic differentiation of HEL cells. Treatment of these cells with 10
      nmol/L phorbol 12-myristate 13-acetate (PMA) for 3 days caused a complete
      inhibition of proliferation and a threefold increase in the surface expression of
      glycoprotein (GP) IIIa, a marker of megakaryocytic differentiation that forms
      part of the fibrinogen receptor complex, GPIIb/IIIa. A similar effect was
      observed with phorbol 12,13-dibutyrate, but not with the biologically inactive
      derivative PMA-4-O-methyl ether. The PMA-induced increase in GPIIIa expression
      was completely inhibited by GF109203X in a dose-dependent manner (IC50 = 0.5
      mumol/L), with a maximal effect at 2.5 to 5.0 mumol/L. GF109203X also blocked the
      inhibitory effect of PMA on cell growth and inhibited PMA-stimulated
      phosphorylation of the 47-kD PKC substrate, pleckstrin. Incubation of HEL cells
      with 25 mumol/L hemin for 3 days caused a fourfold to fivefold increase in
      expression of the erythroid differentiation marker, glycophorin A. In contrast to
      the inhibitory effect of GF109203X on GPIIIa expression, hemin induction of
      glycophorin A was enhanced by this compound. Furthermore, GF109203X alone caused
      a dose-dependent increase in glycophorin A expression, and induced
      hemoglobinization. Consistent with these changes, Northern blot analysis revealed
      that GF109203X treatment reduced the steady-state level of GPIIb mRNA and
      increased those for glycophorin A and gamma-globin. These results suggest that
      PKC may act as a developmental switch controlling erythroid/megakaryocytic
      differentiation.

PMID- 8547634
TI  - Specific involvement of tyrosine 764 of human granulocyte colony-stimulating
      factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2
      complexes.
AB  - Signal transduction from the granulocyte colony-stimulating factor receptor (G
      CSF-R) occurs via multiple pathways, one of which involves activation of p21Ras
      and mitogen-activated protein kinase. The SH2 domain-containing proteins Shc and
      GRB2 have been implicated in this latter signaling route. We studied the role of
      these proteins in signal transduction from wild type (WT) G-CSF-R, C-terminal
      deletion mutants, and tyrosine-to-phenylalanine substitution mutants in
      transfectants of the mouse pro-B cell line, BAF3. G-CSF stimulation of BAF3 cells
      expressing WT G-CSF-R induced tyrosine phosphorylation of Shc. Anti-Shc
      antibodies co-immunoprecipitated tyrosine-phosphorylated 145-kD proteins (p145),
      whereas GRB2 immunoprecipitates contained phosphorylated Shc, Syp, and proteins
      of 145 and 90 kD (p90). Neither of these complexes were detected after activation
      of a C-terminal deletion mutant of G-CSF-R that lacked all four conserved
      cytoplasmic tyrosine residues. G-CSF induced formation of Syp/GRB2 complexes in
      all the tyrosine-substitution mutants, suggesting that this association did not
      depend on the presence of single specific tyrosine residues in G-CSF-R. In
      contrast, tyrosine 764 of G-CSF-R appeared to be exclusively required for
      tyrosine phosphorylation of Shc and its association with p145 and GRB2. In
      addition, tyrosine 764 also specifically mediated binding of GRB2 to p90 without
      the involvement of Shc. These findings indicate that tyrosine 764 of G-CSF-R has
      a prominent role in G-CSF signal transduction.

PMID- 8547635
TI  - PAI-1-resistant t-PA: low doses prevent fibrin deposition in rabbits with
      increased PAI-1 activity.
AB  - The present study compared the activities of recombinant tissue-type plasminogen
      activator (t-PA) and a plasminogen activator inhibitor-1 (PAI-1)-resistant
      variant t-PA (Kt-PA, KHRR 296-299 AAAA) in preventing renal fibrin deposition in
      rabbits with elevated PAI-1 activity. In this model, all rabbits were infused
      with endotoxin (10 micrograms/kg), followed by initiation of thrombin (130 U/kg)
      4 hours later, when plasma PAI-1 activity was greater than 200 arbitrary units
      (AU)/mL (baseline, < 3 AU/mL). Thirty minutes after completion of the 1-hour
      thrombin infusion, rabbits were killed and the kidneys fixed and stained for
      identification of fibrin deposition. Rabbits received one of the following
      treatments initiated 30 minutes before thrombin and continued during the 1-hour
      thrombin infusion: (1) saline (n = 7); (2) low-dose t-PA (17 micrograms/kg, n =
      4); (3) higher-dose t-PA (170 micrograms/kg, n = 4); or (4) low-dose Kt-PA (17
      micrograms/kg, n = 6). Fibrin deposition occurred in 86% and 100% of the rabbits
      receiving saline or low-dose t-PA, respectively. Fibrin deposition did not occur
      in any of the rabbits receiving low-dose Kt-PA or higher-dose t-PA. Low-dose Kt
      PA and higher dose t-PA also caused a reduction in fibrin deposition when infused
      after thrombin administration had been completed. The data provide in vivo
      evidence that Kt-PA is more effective than t-PA in preventing fibrin deposition
      in an animal model that combines thrombogenic stimulation with increased PAI-1
      activity.

PMID- 8547636
TI  - Four novel mutations in deficiency of coagulation factor XIII: consequences to
      expression and structure of the A-subunit.
AB  - The characterization of naturally occurring mutations is one way to approach
      functionally significant domains of polypeptides. About 10 mutations have been
      reported in factor XIII (FXIII) A-subunit deficiency, but very little is known
      about the effects of the mutations on the expression or the structure of this
      enzyme. In this study, the recent crystallization of FXIII A-subunit and
      determination of the three-dimensional model were used for the first time to
      pursue the structural consequences of mutations in the A-subunit. The molecular
      analysis of four families from Sweden, Germany, and Denmark revealed four
      previously unreported point mutations. Three of the mutations were missense
      mutations, Arg326-->Gln, Arg252-->Ile, and Leu498-->Pro, and one was a nonsense
      mutation, a deletion of thymidine in codon for Phe8 resulting in early frameshift
      and premature termination of the polypeptide chain. In the case of the nonsense
      mutation, delT Phe8, the steady-state mRNA level of FXIII A-subunit was reduced,
      as quantitated by reverse transcriptase-polymerase chain reaction and solid-phase
      minisequencing. In contrast, none of the missense mutations affected mRNA levels,
      indicating the possible translation of the mutant polypeptides. However, by
      enzyme-linked immunosorbent analysis and immunofluorescence, all the patients
      demonstrated a complete lack of detectable factor XIIIA antigen in their
      platelets. In the structural analysis, we included the mutations described in
      this work and the Met242-->Thr mutation reported earlier by us. Interestingly, in
      the three-dimensional model, all four missense mutations are localized in the
      evolutionarily conserved catalytic core domain. The substitutions are at least 15
      A away from the catalytic cleft and do not affect any of the residues known to be
      directly involved in the enzymatic reaction. The structural analyses suggest that
      the mutations are most likely interfering with proper folding and stability of
      the protein, which is in agreement with the observed absence of detectable FXIIIA
      antigen. Arg326, Arg252, and Met242 are all buried within the molecule. The
      Arg326-->Gln and Arg252-->Ile mutations are substitutions of smaller, neutral
      amino acids for large, charged residues. They disrupt the electrostatic balance
      and hydrogen-bonding interactions in structurally significant areas. The Met242-
      >Thr mutation is located in the same region of the core domain as the Arg252-
      >Ile site and is expected to have a destabilizing effect due to an introduction
      of a smaller, polar residue in a tightly packed hydrophobic pocket. The
      substitution of proline for Leu498 is predicted to cause unfavorable interatomic
      contacts and a disruption of the alpha-helix mainchain hydrogen-bonding pattern;
      it is likely to form a kink in the helix next to the dimer interface and is
      expected to impair proper dimerization of the A-subunits. In the case of all four
      missense mutations studied, the knowledge achieved from the three-dimensional
      model of crystallized FXIII A-subunit provides essential information about the
      structural significance of the specific residues and aids in understanding the
      biologic consequences of the mutations observed at the cellular level.

PMID- 8547637
TI  - Protein kinase C regulates tyrosine phosphorylation of pp125FAK in platelets
      adherent to fibrinogen.
AB  - Platelet adhesion to immobilized fibrinogen stimulates the induction of tyrosine
      phosphorylation of multiple proteins. However, platelet spreading and tyrosine
      phosphorylation of three proteins, the focal adhesion kinase pp125FAK and
      proteins of 101 and 105 kD (pp101 and pp105), require a second adenosine
      diphosphate (ADP)-dependent costimulatory event. In this study we show that
      protein kinase C (PKC) inhibitors prevented the induction of tyrosine
      phosphorylation of pp125FAK, pp101 and pp105, and abolished spreading. These
      inhibitory effects were not observed after treatment of the platelets with the
      intracellular Ca2+ chelator BAPTA-AM. This suggested that in platelets, PKC
      regulates spreading and related protein tyrosine phosphorylation. In addition,
      the inhibitory effects of apyrase, an ADP scavenger, on spreading and tyrosine
      phosphorylation of pp125FAK, pp101, and pp105, were not observed in the presence
      of phorbol 12-myristate 13-acetate (PMA). These data implied that in fibrinogen
      adherent platelets integrin ligation and an agonist receptor occupancy are
      required for the functional association of PKC and the alpha IIb beta 3-mediated
      signaling pathways. Taken together these results show that PKC plays a central
      role in the transduction of intracellular signals downstream from alpha IIb beta
      3 that regulate spreading and pp125FAK phosphorylation.

PMID- 8547638
TI  - Increase in cytosolic calcium upregulates the synthesis of type 1 plasminogen
      activator inhibitor in the human histiocytic cell line U937.
AB  - In the U937 histiocytic cell line, we investigated the effect of calcium
      mobilizing agents with or without tumor necrosis factor-alpha (TNF) on the
      regulation of the synthesis of plasminogen activator inhibitor-type 1 (PAI-1).
      Cultured U937 cells were stimulated with ionophore A23187 and thapsigargin with
      or without TNF. The response was analyzed in terms of cytosolic calcium
      mobilization, PAI-1 accumulation in the medium, and PAI-1 mRNA expression. The
      study was extended to urokinase (uPA) secretion and surface expression of its
      receptor (uPAR). Using Fluo-3 as a calcium-indicator dye to measure cytosolic
      calcium mobilization, we showed by flow cytometry that both agents mobilized
      calcium in a dose-dependent manner. TNF provoked a slight calcium mobilization
      that was also observed by digital imaging microscopy. Association of TNF with the
      calcium-mobilizing agents potentiated the calcium mobilization. Both calcium
      mobilizing agents induced at 18 hours a dose-dependent accumulation of PAI-1 in
      culture medium, whereas uPA was not affected. TNF alone induced a more marked
      accumulation of PAI-1 than of uPA. Association of TNF with the agents induced a
      PAI-1 response that was more than additive of the two, whereas the secretion of
      uPA was not enhanced. Membrane expression of uPAR, measured by flow cytometry,
      tended to be slightly augmented by the calcium-mobilizing agents only. All the
      treatments resulted in a significant increase in PAI-1 mRNA level at 3 hours
      after the stimulation, which was very marked when calcium-mobilizing agents were
      present. Incubation of U937 cells in a calcium-free medium totally prevented both
      the mRNA expression and accumulation of PAI-1 induced by calcium-mobilizing
      agents and, to lesser extent, that induced by TNF. The increase in PAI-1 mRNA
      expression did not require de novo protein synthesis, as cycloheximide did not
      suppress the increase in PAI-1 mRNA induced by calcium-mobilizing agents. It is
      concluded that, in U937 cells, calcium triggers a pathway that upregulates PAI-1
      synthesis and positively interacts with the TNF-induced pathway that stimulates
      PAI-1 synthesis. As uPA and uPAR were differently affected, it is suggested that
      an increase in cytosolic calcium leads to a reduced pericellular proteolysis.

PMID- 8547639
TI  - Tissue factor mRNA expression in the endothelium of an intact umbilical vein.
AB  - Tissue factor (TF) mRNA expression was measured by in situ hybridization in the
      endothelium of the intact human umbilical vein after infection with Rickettsia
      rickettsii. At 4 hours, R rickettsii organisms were clearly visible within
      approximately 70% of endothelial cells by immunocytochemical staining.
      Quantitation of TF mRNA expression revealed that the level within endothelial
      cells of the infected vein was significantly greater (3.7-fold, P < .0001) than
      that detected in uninfected endothelial cells. Serial sections of the umbilical
      cord vein were processed for in situ hybridization, and immunocytochemical
      staining and showed TF expression in those endothelial cells that contained R
      rickettsii organisms. Immunocytochemical staining for TF antigen at 6 hours was
      negative, but TF was clearly demonstrated within macrophages and fibroblasts of
      both control and infected umbilical cords. These studies demonstrate that the
      vascular endothelial cell, ex vivo, can be directly induced to express TF mRNA.
      This observation has not heretofore been clearly demonstrated except for in
      cultured endothelial cells. Since R rickettsii infection induces thrombotic
      vascular occlusions in patients with Rocky Mountain Spotted Fever, the results
      imply a potential role for endothelial cell TF in the pathogenesis of thrombotic
      disease.

PMID- 8547640
TI  - Human natural killer cell expansion is regulated by thrombospondin-mediated
      activation of transforming growth factor-beta 1 and independent accessory cell
      derived contact and soluble factors.
AB  - Natural killer cells (NK) were studied to determine factors important in their
      expansion. Flourescence-activated cell sorter (FACS) purified CD56+/CD3- NK cells
      cultured alone for 18 days in rIL-2 containing medium (1,000 U/mL) showed
      enhanced cytotoxicity but only minimal expansion. NK expansion was increased
      (12.5 +/- 1.6-fold) by coculturing NK with soluble factors produced by irradiated
      peripheral blood mononuclear cells (PBMNC) in which the two populations were
      separated by a microporous membrane. However, maximal NK expansion was always
      observed when NK were cocultured in direct contact with irradiated PBMNC (49.4 +/
      5.9-fold). To determine if marrow stroma, which supports differentiation of
      primitive NK progenitors, was a better accessory cell population than irradiated
      PBMNC, NK were cocultured in direct contact with primary marrow stromal layers.
      NK expansion with marrow stroma was similar to PBMNC. Fibroblast cell lines (M2
      10B4, NRK-49F, NIH-3T3) and human umbilical vein endothelial cells (HUVEC), all
      homogeneous populations and devoid of monocytes, also exhibited a similar contact
      dependent increase in NK expansion. Experiments were designed using fixed M2-10B4
      stromal cells to separate the contact-induced proliferative stimuli from soluble
      factors. NK plated directly on ethanol/acetic acid-fixed M2-10B4, which leaves
      stromal ligands (cell membrane components and ECM) intact, resulted in increased
      NK expansion compared with medium alone. We further show that the combination of
      independent contact and soluble factors is responsible for maximal late NK
      expansion (days 28 through 40) but paradoxically inhibits early NK expansion (day
      7). The proliferation inhibitory effects were verified by 3H-thymidine uptake and
      could be detected at days 2 through 6 but no longer 14 days after the initiation
      of the culture. We show that both laminin and thrombospondin inhibit early NK
      proliferation, whereas only thrombospondin was capable of also stimulating late
      NK expansion. The effect of thrombospondin on early NK proliferation is related
      to activation of transforming growth factor-beta 1 (TGF-beta) because anti-TGF
      beta neutralizing antibody completely abrogated thrombospondin-mediated
      inhibition of early NK proliferation. Although inhibitory early in culture,
      active TGF-beta added only at culture initiation increases late NK expansion
      similar to thrombospondin. TGF-beta was not present in the thrombospondin
      preparation but latent TGF-beta in serum, or TGF-beta transcripts identified in
      IL-2-activated NK could explain paracrine or autocrine mechanisms for the
      regulation of NK proliferation. Finally, anti-TGF-beta neutralizing antibody only
      minimally affects stroma-mediated inhibition of early NK proliferation suggesting
      that aside from thrombospondin/TGF-beta, additional contact factors are important
      for the regulation of NK proliferation.

PMID- 8547641
TI  - Regulated expression and function of CD122 (interleukin-2/interleukin-15R-beta)
      during lymphoid development.
AB  - To determine whether signaling via CD122 (interleukin-2 [IL-2]/IL-15 receptor
      beta-chain) plays a role in regulating the expansion and differentiation of
      lymphocyte precursors, we have characterized its expression and evaluated its
      ability to influence the activity of developing lymphoid cells. A significant
      fraction of Sca1+Lin- hematopoietic stem cells in day 12 fetal liver were found
      to be CD122+. CD122-mRNA+ and IL-2-mRNA+ cells were also localized in embryo
      sections within pharyngeal blood vessels adjacent to and surrounding the thymic
      analgen. This distribution is consistent with the migration of CD122+ progenitor
      cells from the liver to the developing thymus where a majority of Sca1+
      intrathymic T-cell progenitors were CD122+. Analysis of CD122 expression in the
      day 12 fetal liver revealed that the majority of B220+ cells were CD122+.
      Furthermore, CD122 expression was restricted to the earliest B220+ cells
      (CD43+CD24-; prepro B cells; fraction A) that proliferate vigorously to IL-2 in
      the absence of any stromal cells, but not to IL-15. Consistent with a role for
      the IL-2/IL-2R pathway in lymphocyte development is the progressive loss of B
      cells seen in IL-2-deficient mice. Together, these observations suggest that
      CD122 plays a role in regulating normal lymphocyte development in vivo.

PMID- 8547642
TI  - Recombinant scinderin, an F-actin severing protein, increases calcium-induced
      release of serotonin from permeabilized platelets, an effect blocked by two
      scinderin-derived actin-binding peptides and phosphatidylinositol 4,5
      bisphosphate.
AB  - In response to vessel injury or exposure to different substances, platelets
      undergo activation which consists of shape changes, formation of cellular
      pseudopodia, aggregation, and secretion. These dramatic changes are accompanied
      by cycles of actin depolymerization and polymerization. Previous work has shown
      the presence in platelets of gelsolin and scinderin, two Ca(2+)-dependent F-actin
      severing proteins. Recent published evidence suggests that scinderin is a
      component of the exocytotic machinery in chromaffin cells. The present work
      describes the preparation of recombinant scinderin and peptides Sc-ABP1 and Sc
      ABP2 with sequences corresponding to two actin-binding sites of scinderin.
      Recombinant scinderin and peptides Sc-ABP1 and Sc-ABP2 were tested for their
      effects on Ca(2+)-induced serotonin release from digitonin permeabilized
      platelets. The results indicated that recombinant scinderin potentiates Ca(2+)
      evoked serotonin release, an effect blocked in the presence of Sc-ABP1, Sc-ABP2,
      exogenous gamma-actin, or the addition of phosphatidylinositol 4,5-bisphosphate
      (PIP2). In the presence of a mismatched peptide (MMP) the potentiating effect of
      recombinant scinderin was not affected. Moreover, Sc-ABP1, Sc-ABP2, and gamma
      actin inhibited Ca(2+)-induced release of serotonin in the absence of recombinant
      scinderin, suggesting an inhibition of platelet endogenous scinderin. MMP was
      ineffective under these conditions. The results suggest that F-actin disassembly,
      perhaps at a specific site, is required for platelet secretion and that scinderin
      might be an important component of the exocytotic machinery in platelets.

PMID- 8547643
TI  - Phosphatidylinositol-3-kinase activity is required for the anti-ig-mediated
      growth inhibition of a human B-lymphoma cell line.
AB  - Stimulation of B lymphocytes through the Ig receptor initiates a cascade of
      biochemical changes, which can ultimately lead to either activation and growth,
      or cell-cycle arrest and cell death. One of the critical events that occurs in
      both cases is the activation of tyrosine kinases, and the resulting
      phosphorylation of a variety of proteins on tyrosine residues. In this report we
      identify one of the substrates of phosphorylation as the 85-kD subunit of the
      enzyme phosphatidylinositol-3 kinase (PI3K), and show that both anti-IgM and anti
      IgD stimulation results in an increase in the anti-phosphotyrosine-precipitable
      PI3K activity. Furthermore, we show that the potent and specific inhibitor of
      PI3K, Wortmannin, can completely abrogate anti-Ig-mediated growth inhibition
      without affecting tyrosine kinase induction or protein kinase C (PKC) activation.
      Treatment of intact cells with Wortmannin results in an irreversible decrease in
      anti-Ig-induced PI3K activity, suggesting that the effect of Wortmannin on anti
      Ig-mediated growth inhibition is caused by its inactivation of PI3K activity.
      Taken together, these data show that activation of PI3K is a critical component
      of the anti-Ig-initiated signaling cascade that leads to growth inhibition of
      human B lymphoma cells.

PMID- 8547644
TI  - Differential regulation of vascular cell adhesion molecule-1 gene transcription
      by tumor necrosis factor alpha and interleukin-1 alpha in dermal microvascular
      endothelial cells.
AB  - As part of the inflammatory response, the localization of leukocytes depends to
      an important degree on cytokine-induced expression of vascular cell adhesion
      molecule-1 (VCAM-1) on endothelial cells (EC). We have previously shown that VCAM
      1 expression is induced on human umbilical vein EC (HUVEC) by both tumor necrosis
      factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha), whereas on human
      dermal microvascular EC (HDMEC) only TNF alpha results in VCAM-1 expression. To
      explore molecular mechanisms responsible for these contrasting patterns of VCAM-1
      induction in HUVEC versus HDMEC, we performed transcriptional activation studies
      with VCAM-1-based reporter constructs and in vitro binding assays using two
      adjacent NF-kappa B binding sequences of the VCAM-1 promoter as a DNA probe.
      Previous studies have established that these NF-kappa B motifs are required for
      cytokine-induced VCAM-1 transcription, and may further mediate cell-specific VCAM
      1 gene activation by cytokines. The findings reported here demonstrate a
      significant HDMEC-specific attenuation of VCAM-1 gene transcription in response
      to IL-1 alpha, but not TNF alpha. An upstream VCAM-1 gene regulatory region
      distinct from the NF-kappa B sites appears to function as an IL-1 alpha-mediated
      transcriptional repressor within HDMEC. This repressor region conveys IL-1 alpha
      dependent, but not TNF alpha-dependent, inhibition of transcription driven by a
      heterologous cytokine response element and promoter.

PMID- 8547645
TI  - Probing the pathobiology of response to all-trans retinoic acid in acute
      promyelocytic leukemia: premature chromosome condensation/fluorescence in situ
      hybridization analysis.
AB  - The response of acute promyelocytic leukemia (APL) peripheral blood and bone
      marrow cells to trans-retinoic acid (RA) was cytogenetically characterized during
      RA treatment using the techniques of premature chromosome condensation (PCC) and
      fluorescence in situ hybridization (FISH). Before treatment, the predominant
      immature bone marrow cells were found to have t(15;17), whereas the residual
      mature granulocytes were diploid and lacked evidence of the translocation. In
      response to RA treatment, an increase in the leukocyte count was noted. The
      majority of these cells exhibited a t(15;17). Subsequently (eg, between days 6
      and 23), 32% to 91% of the maturing myeloid cells still exhibited t(15;17). The
      appearance of t(15;17) in gradually maturing elements suggests that RA
      contributed to a release of the maturation block of the leukemic elements. As
      responding patients obtained complete remission, diploid elements without
      evidence of the translocation prevailed in the blood and bone marrow. In 16
      patients studied after 1 month in complete remission, all but 2 showed all
      diploid cells. The residual t(15;17) cells disappeared 18 days later in 1
      patient, whereas the second patient exhibited clinical evidence of relapse 20
      days later. These results suggest that response of patients with APL to RA is
      associated with maturation, subsequent loss of the mature leukemic elements, and
      preferential regeneration of normal diploid hematopoietic elements.

PMID- 8547646
TI  - Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells
      induced by retinoic acid receptor- and retinoid X receptor-selective retinoic
      acid analogs.
AB  - The ability of subtypes of retinoic acid receptors (RARs) and retinoid X
      receptors (RXRs) singly and in combination to elicit myeloid differentiation,
      G1/0-specific growth arrest, and retinoblastoma (RB) tumor suppressor protein
      dephosphorylation was determined in the human myeloblastic leukemia cell line HL
      60 using subtype-selective retinoic acid (RA) analogs. RA analogs that
      selectively bind only to RARs (Am580 and/or TTNPB) or to RXRs (Ro 25-6603,
      SR11237, and/or SR11234) did not elicit the above-mentioned three cellular
      responses. In contrast, simultaneous treatment with both an RAR-selective ligand
      (Am580 or TTNPB) and an RXR-selective ligand (Ro 25-6603, SR11237, or SR11234)
      induced all three cellular processes. An RAR alpha-selective ligand used with an
      RXR-selective ligand generated the same responses as did all-trans RA or 9-cis
      RA, which affect both families of receptors, suggesting an important role for RAR
      alpha among RAR subtypes in eliciting cellular response. Consistent with this
      finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of the cellular
      responses elicited by treatment with an RAR alpha-selective ligand plus RXR
      selective ligand. The coupling of the shift of RB to its hypophosphorylated form
      with G1/0 arrest and differentiation in response to ligands is consistent with a
      possible role of RB as a downstream target or effector of RAR alpha and RXR in
      combination.

PMID- 8547647
TI  - The BCR-ABL oncogene requires both kinase activity and src-homology 2 domain to
      induce cytokine secretion.
AB  - Expression of either the BCR-ABL or the v-abl oncogene in the factor-dependent
      murine myeloid cell line FDCP-1 results in growth factor independence. Studies
      with temperature-sensitive mutants of v-abl show that this growth factor
      independence is oncogene dependent. Likewise, cells expressing a kinase inactive
      mutant of BCR-ABL did not grow in the absence of interleukin-3 (IL-3).
      Conditioned media from cells expressing either v-abl or BCR-ABL contained growth
      factor(s) capable of stimulating the proliferation of uninfected FDCP-1 cells.
      Based on enzyme-linked immunosorbent assay studies and antibody neutralization
      studies, the major growth factor present in these conditioned media is IL-3.
      Because of the importance of SH2 domains in regulating substrate interactions, we
      examined the ability of SH2 deletion mutants in BCR-ABL to induce growth factor
      independence. Cells expressing a mutant of BCR-ABL lacking the SH2 domain were
      growth factor independent; however, they did not secrete growth factors. This
      finding suggests that while IL-3 produced by cells infected with BCR-ABL may
      contribute to autocrine or paracrine growth factor independence, expression of an
      activated tyrosine kinase alone may be able to induce growth factor independence.
      Furthermore, the secretion of cytokines maybe correlated with a specific region
      of the BCR-ABL oncogene, suggesting that activation (phosphorylation) of specific
      substrates may be critical for transcriptional activation of cytokine genes.

PMID- 8547648
TI  - Human leukemia cell lines bind basic fibroblast growth factor (FGF) on FGF
      receptors and heparan sulfates: downmodulation of FGF receptors by phorbol ester.
AB  - Basic fibroblast growth factor (bFGF) has been identified as an important
      cytokine for blood cells. To determine whether hematopoietic cells have receptors
      that recognize bFGF, the ability of human leukemia cell lines to bind 125I-bFGF
      was investigated. Specific bFGF-binding sites were identified on K562 and HL60
      cells, but not on U937 cells. DAMI cells bound low amounts of 125I-bFGF
      specifically. Binding of 125I-bFGF to K562 cell surfaces was reduced in a dose
      dependent manner by unlabeled bFGF or by heparin. Scatchard analysis of binding
      to K562 cells revealed two classes of binding sites: 1,650 high affinity binding
      sites per cell with a dissociation constant (kd) of 192 pmol/L, and 36,600 low
      affinity sites per cell with a kd of 9.3 nmol/L. Chemical crosslinking
      experiments with K562, HL60, and DAMI cells revealed receptor-growth factor
      complexes with molecular masses of 140 to 160 kD, similar in size to complexes
      formed by known receptor species. Binding of 125I-bFGF to K562 cells was
      sensitive to heparinase treatment but not to chondroitinase treatment, suggesting
      that heparan sulfate proteoglycans (HSPGs) may be responsible for the low
      affinity binding sites. To further investigate whether K562 cells make HSPG, the
      incorporation of 35SO4 into proteoglycans was assessed. Metabolically labeled
      cell-surface proteoglycans with molecular masses of 180 to 300 kD were identified
      in K562 cells. These proteoglycans were sensitive to heparinase, demonstrating
      that K562 cells synthesize bFGF-binding HSPG. Treatment of K562 cells with
      phorbol-12-myristate-13-acetate (PMA) caused a loss of bFGF-binding capacity.
      This decreased binding capacity reflected a rapid loss of high affinity
      receptors. The ability to form bFGF-receptor complexes decreased by 65% to 70%
      within 1 hour and declined continuously thereafter. The decrease in binding of
      bFGF was not due to an autocrine downregulation of bFGF receptors, because there
      was no increase in bFGF after PMA treatment as detected by Western blotting, and
      suramin, which blocks bFGF binding to receptors, did not prevent the loss of
      receptors after exposure to PMA. In addition, inhibitors of either protein
      synthesis or protease activity did not prevent the loss of bFGF receptors in PMA
      treated cells. In summary, this work demonstrates that leukemia cell lines have
      receptors that specifically bind bFGF and supports the hypothesis that bFGF acts
      directly on certain blood cells to stimulate their proliferation.

PMID- 8547649
TI  - REL proto-oncogene is frequently amplified in extranodal diffuse large cell
      lymphoma.
AB  - Comparative genomic hybridization (CGH) analysis of DNA extracted from a diffuse
      lymphoma with a large cell component (DLLC) that displayed double minute
      chromosomes upon conventional karyotypic analysis indicated overt amplification
      of DNA sequences derived from the 2p13-15 region. Southern blot analysis of this
      tumor DNA with a cDNA probe for the proto-oncogene REL, previously mapped to 2p14
      15, indicated a greater than 35-fold amplification of REL. To determine the
      incidence of REL amplification and possible clinical or histologic association
      with DLLC, a panel of 111 tumor DNAs from DLLC specimens was screened for REL
      amplification by Southern blot analysis. A copy number of > or = 4 was noted in
      26 cases (23%). Southern blot analysis of these 26 tumor DNAs with a cDNA probe
      for TGFA, mapped to 2p13, indicated lack of coamplification except in one case.
      Another member of the Rel/NF-kappa B family of transcriptional activators,
      RELA/p65 mapped to 11q13, was amplified in five cases as determined by Southern
      blot analysis using a cDNA probe. Nineteen of the 26 DLLC (73%) with REL
      amplification were primary extranodal lymphomas. As a group, the tumors with REL
      amplification demonstrated an increased frequency of chromosomal aberrations
      previously associated with tumor progression, suggesting an oncogenic effect of
      amplified REL in B-lymphoid cells that already contained a transforming genetic
      lesion. Thus, REL amplification is a frequent event in DLLC, and probably
      constitutes a progression-associated marker of primary extranodal lymphomas. This
      study shows the usefulness of the CGH technique in identifying chromosomal
      regions overrepresented in tumors that can point to amplified genes and may be
      correlated with clinical features of the disease.

PMID- 8547650
TI  - Chlorodeoxyadenosine and arabinosylcytosine in patients with acute myelogenous
      leukemia: pharmacokinetic, pharmacodynamic, and molecular interactions.
AB  - The effectiveness of arabinosylcytosine (ara-C) for the treatment of acute
      myelogenous leukemia (AML) depends on the formation of its active metabolite, the
      triphosphate of ara-C (ara-CTP). Using biochemical modulation strategies to
      increase the accumulation of ara-CTP in leukemia blasts, a clinical protocol was
      designed combining 2-chlorodeoxyadenosine (CdA), an inhibitor of ribonucleotide
      reductase, and ara-C for adults with AML. The protocol stipulated an infusion of
      1 g/m2 of ara-C over 2 hours on day 1. A continuous infusion of CdA (12 mg/m2/d)
      begun 24 hours later and continued for 5 days. Identical doses of ara-C were
      administered on days 3, 4, 5, and 6. Pharmacokinetic and pharmacodynamic
      interactions between CdA and ara-C during therapy were investigated. To
      complement these studies, molecular actions of the triphosphate of ara-C and CdA
      on DNA extension by human DNA polymerase alpha in an in vitro model system was
      conducted. In the circulating leukemia blasts of 7 of the 9 patients studied, ara
      CTP pharmacokinetics showed a median 40% increase in the rate of ara-CTP
      accumulation after 24 hours of CdA infusion. The ex vivo effect of CdA on
      accumulation of ara-CTP in AML blasts was similar to that during therapy except
      that the enhancement was less. The DNA synthetic capacity of the circulating
      blasts was inhibited to a greater extent by administration of CdA and ara-C in
      combination than by either one alone. Additionally the lowered level of DNA
      synthesis was maintained until the next infusion of ara-C. Endogenous levels of
      deoxynucleotides increased 24 hours after ara-C infusion. Administration of CdA
      in general lowered the concentrations of all dNTPs. DNA pol alpha incorporated
      CdATP and ara-CTP with high affinity in a DNA primer extending over an
      oligonucleotide template of defined sequence. Human DNA polymerase alpha extended
      DNA primers terminated by CdA monophosphate (CdAMP) at its 3'-end by
      incorporating ara-C monophosphate (ara-CMP). The tandem incorporation of CdAMP
      and ara-CMP resulted in nearly complete inhibition of DNA primer extension. The
      insertion of two analogs in sequence, inhibition of ribonucleotide reductase, and
      the metabolic potentiation of ara-CTP by CdA infusion may be responsible for
      sustained inhibition of DNA synthesis in the circulating leukemia blasts during
      therapy with this combination regimen.

PMID- 8547651
TI  - Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's
      lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).
AB  - Little is known about the expression of bcl-2 protein in intermediate and high
      grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance.
      We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue
      sections of 348 patients with high or intermediate grade NHL. These patients were
      uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and
      prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight
      cases were excluded due to inadequate staining. Of the 290 remaining patients,
      131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually
      all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited
      intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109
      of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was
      heterogeneously distributed among the different histological subtypes. Further
      analysis was performed on the 151 patients with diffuse large B-cell lymphoma
      (centroblastic and immunoblastic) to assess the clinical significance and
      potential prognostic value of bcl-2 expression in the most frequent and
      homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of
      these patients (67 of 151), was more frequently associated with III-IV stage
      disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall
      survival (P < .05) were demonstrated in the patients with high bcl-2 expression.
      Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%,
      respectively (high bcl-2 expression) versus 82% and 78%, respectively
      (negative/intermediate bcl-2 expression). A multivariate regression analysis
      confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2
      protein expression, as demonstrated in routinely paraffin-embedded tissue,
      appears to be predictive of poor DFS, in agreement with the role of bcl-2 in
      chemotherapy-induced apoptosis. It might be considered as a new independent
      biologic prognostic parameter, which, especially in diffuse large B-cell NHL,
      could aid in the identification of patient risk groups.

PMID- 8547652
TI  - Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by
      deletion of seven amino acids at the juxtamembrane domain.
AB  - A peculiar point mutation results in constitutive activation of c-kit receptor
      tyrosine kinase (KIT) in three different tumor mast cell lines; ie, the HMC-1, P
      815, and RBL-2H3. Because constitutive activation of KIT was also observed in the
      FMA3 mouse mastocytoma cell line, we investigated the molecular mechanism.
      Sequencing of the whole coding region of the c-kit showed that the point mutation
      found in HMC-1, P-815, and RBL-2H3 cells was absent in FMA3 cells and that the c
      kit cDNA of FMA3 cells carried an in-frame deletion of 21 base pairs (bp)
      encoding Thr-Gln-Leu-Pro-Tyr-Asp-His at codons 573 to 579 at the juxtamembrane
      domain. The FMA3-type c-kit cDNA with 21 bp deletion was introduced into the IC-2
      cell line, which was derived from murine cultured mast cells. IC-2 cells were
      dependent on interleukin (IL)-3 and did not express KIT on the surface. In IC-2
      cells introduced with the FMA3-type c-kit cDNA, KIT was constitutively
      phosphorylated on tyrosines and activated. Moreover, the FMA3-type KIT was
      dimerized without the stimulation by stem cell factor (SCF), a ligand for KIT.
      The spontaneously dimerized FMA3-type KIT without SCF binding was not
      internalized even after the activation. IC-2 cells expressing the FMA3-type KIT
      grew in suspension culture without IL-3 and SCF and became leukemic in nude
      athymic mice. The deletion of seven amino acids at the juxtamembrane domain
      appeared to be a new activating mutation of KIT that might be involved in
      neoplastic growth of mast cells.

PMID- 8547653
TI  - High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell
      lymphoma and its lack of detection in Hodgkin's disease. Comparison of
      cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80
      immunostaining.
AB  - Fifty-six cases of anaplastic large cell lymphoma (ALCL), 23 cases of Hodgkin's
      disease, and 16 cases of diffuse large cell lymphoma were investigated for the
      t(2;5)(p23;q35) translocation. The translocation was detected by using
      cytogenetic analysis, reverse transcriptase-polymerase chain reaction (RT-PCR)
      and immunohistochemistry with P80 antibody directed against the kinase domain of
      anaplastic lymphoma kinase (ALK) of the chimeric NPM/ALK protein. In all but
      three cases of ALCL, we found an agreement between cytogenetic analysis, RT-PCR,
      and P80 staining. However, in one case, the t(2;5) translocation was detected
      with cytogenetic analysis, but RT-PCR and P80 staining were found to be negative.
      Conversely, in another case the karyotype was normal, but the hybrid mRNA and P80
      staining were found to be positive. In one case, malignant cells showed a
      translocation involving chromosomes 1q25 and 2p23 and were strongly positive for
      P80 staining. Such a result could be expected because P80 antibody detects the
      kinase domaine of the ALK protein encoded by chromosome 2p23. Overall 73.2% (41
      of 56) of cases were found to be positive. However, the highest percentage (23 of
      26 cases; 88.5%) of P80 positive cases was found in children compared with 60%
      (18 of 30 cases) in adult ALCL (P < .05). In Hodgkin's disease, Reed-Sternberg
      cells were found to be clearly negative by RT-PCR and with P80 antibody. The
      latter results suggest that Hodgkin's disease and t(2;5)-positive ALCL are
      distinct biological entities and that the demonstration of the t(2;5)
      translocation is of diagnostic importance in differentiating these two entities.
      The results of the present study indicate that immunohistochemistry with P80
      antibody is a reliable method for detecting NPM/ALK chimeric protein.

PMID- 8547654
TI  - Tumor-specific rearrangements of the immunoglobulin heavy-chain gene in B-cell
      non-Hodgkin's lymphoma detected by in situ hybridization.
AB  - We have recently described the potential use of fluorescence in situ
      hybridization (FISH) to detect tumor-specific rearrangements of the
      immunoglobulin heavy-chain (IgH) gene in interphase nuclei. Using yeast
      artificial chromosome (YAC) clone Y6 containing variable region (VH) gene and
      bacteriophage clones Ig gamma, we analyzed 70 patients with B-cell non-Hodgkin's
      lymphoma (NHL) and compared the results with those obtained by the conventional G
      banding method. Tumor-specific rearrangements of the IgH gene equivalent to 14q32
      translocations were defined as separate signals of VH and Ig gamma genes or those
      of Ig gamma genes and referred to split signals. Twenty-nine patients (41.4%)
      showed split signals. Among these, 13 did not show 14q32 translocations by G
      banding: three with other chromosomal abnormalities, one with normal karyotype,
      and nine with no analyzable metaphases. The partner sites of 14q32 translocations
      were identified in 17 patients by FISH: t(3;14)(q27;q32) including a complex
      variant was observed in nine patients, t(14;18)(q32;q21) in four,
      t(8;14)(q24;q32) in three, t(14;19)(q32;q13) in one, and t(11;14)(q13;q32) in
      one. Six of nine patients with t(3;14) or its variant and one of three with
      t(8;14) were diagnosed as having respective translocations only by FISH.
      Translocation t(3;14) was found most commonly, and was correlated histologically
      with diffuse lymphoma with large-cell components. These results indicate that
      interphase FISH with IgH gene probes promises to be a rapid and reliable method
      for use in the diagnosis of B-cell NHL.

PMID- 8547655
TI  - Marginal zone B-cell lymphomas of different sites share similar cytogenetic and
      morphologic features.
AB  - Clinical, histologic, cytogenetic, and molecular genetic data of 31 patients with
      extranodal, nodal, and splenic marginal zone B-cell lymphoma (MZBCL) are
      presented. Despite these variable clinical manifestations, a similar spectrum of
      morphologic features as well as distinctive immunophenotypic findings were noted.
      In all cases, a monotypic B-cell proliferation consistently negative for CD5,
      CD10, and CD23 was found expanding the marginal zone of the B follicle with and
      without colonization of the follicle centers. Clonal chromosomal abnormalities
      were detected in 23 of the 31 patients. Recurrent aberrations included whole or
      partial trisomy 3 (18 cases), trisomy 18 (9 cases), and structural rearrangements
      of chromosome 1 with breakpoints in 1q21 (9 cases) or 1p34 (6 cases), all of
      which were seen in extranodal, nodal, as well as splenic MZBCL. Abnormalities of
      the additional chromosome 3, such as +del(3)(p13),+i(3)(q10), or structural
      changes involving the distal part of the long arm, were evident in 9 of the 18
      cases. All recurrent abnormalities were found in MZBCL more frequently than in
      other histologic entities of B-cell non-Hodgkin's lymphoma (B-NHL). None of the
      known lymphoma-associated chromosomal changes or rearrangements of the BCL1,
      BCL2, BCL3, BCL6, and CMYC genes were detected. We conclude that MZBCL represent
      a distinct entity of B-NHL with characteristic morphologic and immunophenotypic
      features and particular chromosomal abnormalities, and that a close histogenetic
      relationship between extranodal, nodal, and splenic MZBCL is likely, although the
      clinical presentation may vary.

PMID- 8547656
TI  - Ex vivo expansion of murine marrow cells with interleukin-3 (IL-3), IL-6, IL-11,
      and stem cell factor leads to impaired engraftment in irradiated hosts.
AB  - In vitro incubation of bone marrow cells with cytokines has been used as an
      approach to expand stem cells and to facilitate retroviral integration. Expansion
      of hematopoietic progenitor cells has been monitored by different in vitro assays
      and in a few instances by in vivo marrow renewal in myeloablated hosts. This is
      the first report of studies, using two competitive transplant models, in which
      cytokine-treated cells, obtained from nonpretreated donors (eg, 5-fluorouracil),
      were competed with normal cells. A basic assumption is that the expansion of
      progenitors assayed in vitro as high- and low-proliferative potential colony
      forming cells (HPP- and LPP-CFCs) indicates an expansion of stem cells which will
      repopulate in vivo. This study shows that culture of marrow cells with four
      cytokines (stem cell factor, interleukin-3 [IL-3], IL-6, IL-11) induces
      significant expansion and proliferation of HPP-CFC and LPP-CFC. Cell-cycle
      analysis showed that these hematopoietic progenitors were induced to actively
      cell cycle by culture with these cytokines. In the first competitive transplant
      model, which uses Ly5.2/Ly5.1 congenic mice, cytokine-cultured Ly5.2 cells
      competed with noncultured Ly5.1 cells led to 5% +/- 1% engraftment at 12 weeks
      and to 4% +/- 2% engraftment at 22 weeks posttransplantation for the cytokine
      exposed cells. Noncultured Ly5.2 cells competed with cultured Ly5.1 cells led to
      70% +/- 1% engraftment at 12 weeks and to 93% +/- 2% engraftment at 22 weeks
      posttransplantation. In the second model, which uses BALB/c marrow of opposite
      genders, cultured male cells lead to 13% +/- 9% engraftment at 10 weeks and 2% +/
      1% engraftment at 14 weeks posttransplantation; noncultured male cells lead to
      70% +/- 2% and 95% +/- 2% engraftment at 10 and 14 weeks posttransplantation,
      respectively. Data presented here from two different competitive transplant
      studies show a defect of cytokine expanded marrow related to cell cycle
      activation which manifests as defective long-term repopulating capability in
      irradiated host mice. The engraftment defect is more profound at longer time
      intervals, suggesting that the most striking effect may be on long-term
      repopulating cells.

PMID- 8547657
TI  - High frequency of acute promyelocytic leukemia among Latinos with acute myeloid
      leukemia.
AB  - A high frequency (24%) of acute promyelocytic leukemia (APL) was noted among
      acute myelocytic leukemia (AML) cases at the Los Angeles County-University of
      Southern California (LAC-USC) Medical Center, in comparison with the expected
      frequency of 5% to 15%. Because of the high proportion of Latinos in this center,
      we questioned if APL is more common in this ethnic group. The proportion of APL
      among the 80 AML patients of Latino origin was significantly higher (30; 37.5%)
      when compared with the 62 non-Latinos (4; 6.5%) (P = .00001). In an attempt to
      verify this finding on a larger group of patients, we analyzed 276 pathologically
      verified cases of AML in patients aged 30 to 69 years from the entire County of
      Los Angeles, registered on an ongoing population-based epidemiologic study of
      AML. APL was more frequent among the 47 Latinos (24.3%) than in the 229 non
      Latinos (8.3%) (P = .0075). APL is seen in younger patients with AML, but Latino
      AML patients also had a higher frequency of APL after accounting for their
      younger age (age-adjusted odds ratio for APL among Latinos in LAC-USC Medical
      Center, 9.4 [95% confidence interval (CI) 2.9, 30] P = .0002; among Latinos in
      the population-based study, 3.0 [95% CI 1.3 to 6.9] P = .01). The different
      ethnic distribution of AML was found to be due to a higher proportion of APL
      cases per se, and not to a lower proportion of any other French-American-British
      subtype (P = .0004). These results, from two different populations of AML
      patients, indicate that Latinos with AML have a higher likelihood of the APL
      subtype of disease, which may suggest a genetic predisposition to APL and/or
      exposure to distinct environmental factor(s).

PMID- 8547658
TI  - Inhibition of myeloma cell growth by dexamethasone and all-trans retinoic acid:
      synergy through modulation of interleukin-6 autocrine loop at multiple sites.
AB  - Interleukin-6 (IL-6)/IL-6 receptor (IL-6R) plays a major role in
      autocrine/paracrine growth regulation of myeloma cells. We investigated the
      effect of dexamethasone and all-trans retinoic acid, previously shown to modulate
      IL-6/IL-6R, on the in vitro growth of a human myeloma cell line, OPM-2. Both
      agents inhibited the clonogenic growth and 3H-thymidine incorporation in a
      concentration-dependent fashion. Isobologram and median effect analysis showed a
      strong synergy between these two agents with a combination index in the range of
      0.2 to 0.6. Both agents decreased the labeling index and the cell fraction in S
      and G2/M phases, suggesting a block in G1-S phase transition. The clonogenic
      growth was stimulated by exogenous IL-6 and was inhibited by monoclonal antibody
      to IL-6, suggesting an autocrine function of IL-6. The effect of dexamethasone
      but not all-trans retinoic acid was completely reversed by exogenous IL-6.
      Dexamethasone increased, while all-trans retinoic acid reduced, IL-6R but not
      gp130 mRNA expression. Their combination caused a net reduction in IL-6R mRNA.
      Cellular IL-6R density was altered correspondingly without changes in the binding
      affinity. IL-6 mRNA expression was reduced by dexamethasone and the combination,
      but was not affected by retinoic acid alone. However, IL-6 secretion into culture
      supernatant was abolished by both agents. A survey of 4 additional human myeloma
      cells showed that 1 was sensitive to both, 1 was sensitive to one agent only, and
      2 were resistant to both. The study demonstrates the possibility of regulating
      myeloma cell growth through modulation of IL-6/IL-6R autocrine/paracrine loop and
      the principle of achieving a synergistic effect by blocking this loop at multiple
      sites.

PMID- 8547659
TI  - Molecular characterization of 12p abnormalities in hematologic malignancies:
      deletion of KIP1, rearrangement of TEL, and amplification of CCND2.
AB  - Twenty patients with hematologic malignancies with 12p abnormalities were
      investigated by fluorescence in situ hybridization (FISH) using probes mapped to
      specific regions in 12p. The initial analysis using the YAC 964c10 (D12S736)
      revealed that all four cases with cytogenetically identified del(12p) had lost
      one copy of this YAC and that submicroscopic deletions had occurred in 10 of the
      16 neoplasms with other 12p abnormalities, ie, translocations, additions, and
      insertions. The deletions were partially mapped with cosmids localized to
      subregions of 12p. One copy of the gene for p27kip1 (KIP1), involved in cell
      cycle entrance, was found to be lost in all cases in which deletions could be
      detected by other probes and in one case with a translocation as the only
      detectable change. This implicates KIP1 as a possible tumor suppressor gene
      affected by del(12p). Four translocations with no apparent concomitant deletions
      were detected. All four breakpoints resulted in a split D12S736 signal. In two of
      these cases, we showed that TEL was disrupted as a result of a t(5;12)(q32
      33;p12) and a t(12;22)(p12;q12), respectively. Two lymphoid neoplasm--one non
      Hodgkin's lymphoma and one Burkitt's lymphoma--with 12p amplifications were
      detected. In both cases cyclin D2 (CCND2) was within the amplified region. Thus,
      cytogenetic abnormalities of 12p in hematologic malignancies result in at least
      three different molecular changes: deletions of KIP1, amplifications of CCND2,
      and structural rearrangements of TEL.

PMID- 8547660
TI  - Human mononuclear cells express 12-LX: coordinated mRNA regulation with 5-LX and
      FLAP genes.
AB  - Lipoxygenases (LXs) catalyze formation of leukotrienes and hydroxy
      eicosatetraenoic acids (HETEs), proinflammatory, and spasmogenic autacoids that
      are critical for host defense systems. We studied the expression and regulation
      of LX genes (12-LX, 5-LX, and 15-LX) and the 5-lipoxygenase activating protein
      (FLAP) in human mononuclear cells (MNC) and granulocytes using a quantitative
      reverse transcription polymerase chain reaction (RT-PCR) technique. We show that
      12-LX mRNA is constitutively expressed in resting platelet-free MNC. 12-LX gene
      expression was upregulated by activation with lipopolysaccharide (LPS). The
      formation of 12-HETE was inducible with ionophore in MNC, as assessed by high
      performance liquid chromatography (HPLC) and gas chromatography, and increased
      after LPS pretreatment. In addition to 12-LX, resting MNC expressed the genes for
      5-LX and FLAP constitutively. Quantitative time course analyses of 12-LX, 5-LX,
      and FLAP gene expression suggested coregulation of 12-LX and FLAP mRNAs, and
      reciprocal regulation of 5-LX and FLAP mRNAs. During cell stimulation with LPS 5
      LX mRNA levels remained unchanged, whereas FLAP gene expression increased. No 15
      LX mRNA expression or 15-HETE formation was detectable in unstimulated and
      activated MNC. In contrast to MNC, quantitative RT-PCR mRNA analysis showed
      intermittent intraindividual expression of the 5-LX and FLAP genes in resting
      granulocytes. mRNAs for 12-LX and 15-LX were not expressed. On stimulation of
      granulocytes ex vivo, mRNA expression of 5-LX and FLAP was upregulated.
      Stimulation by LPS differed from that by ionophore A23187. Neither LPS nor
      ionophore induced gene expression of 12-LX or 15-LX in granulocytes. Our data
      indicate that resting human MNC and granulocytes express LX and FLAP genes in a
      cell-specific manner. Cell activation induces coordinated upregulation of 12-LX
      and FLAP genes in MNC, and 5-LX and FLAP genes in granulocytes, respectively. The
      constitutive expression of 12-LX mRNA, its upregulation on cell activation, and
      the formation of 12-HETE clearly indicate the presence of a functional 12-LX in
      human MNC.

PMID- 8547661
TI  - Cytosolic inactivation of translocated neutrophil plasma membrane protein
      tyrosine phosphatase.
AB  - Phosphotyrosine phosphatases (PTPases) regulate cellular metabolic activation by
      reversing the effects of tyrosine kinases activated earlier in intracellular
      signaling pathways. We coupled fluorescence-activated cell sorter analysis using
      anti-CD45 monoclonal antibody with direct measurements of enzyme activity in
      resolved subcellular fractions to define mechanisms that potentially regulate the
      availability and activity of CD45-PTPase on neutrophil plasma membranes.
      Neutrophils in freshly obtained blood as well as neutrophils freshly isolated
      from blood were found to possess detectable levels of plasma membrane CD45 as
      assessed by immunofluorescence. However, plasma membranes from these cells were
      essentially devoid of PTPase catalytic activity, which was largely confined to
      the specific granules. Granulocyte-macrophage colony-stimulating factor (GM-CSF)
      upregulated both the catalytic and antigenic components of CD45-PTPase on the
      plasma membrane of these cells. Upregulation was associated with a shift in the
      particulate subcellular PTPase catalytic activity from the specific granule
      fraction to the plasma membrane fraction. The tyrosine kinase inhibitor genistein
      abrogated GM-CSF-promoted upregulation of plasma membrane CD45 PTPase but did not
      prevent the GM-CSF-dependent decrease in specific granule catalytic activity.
      Anti-CD45 antibody immunoprecipitated PTPase activity from both specific granules
      of resting cells and plasma membranes of GM-CSF-treated cells. However,
      antiphosphotyrosine immunoprecipitated only activity that had translocated to the
      plasma membrane, suggesting a role for CD45 phosphorylation in translocation.
      Western analysis confirmed the tyrosine phosphorylation of CD45 in plasma
      membranes of GM-CSF-treated neutrophils. Preincubation of plasma membranes of GM
      CSF-stimulated neutrophils with cytosol from resting cells resulted in a time-
      and temperature-dependent loss in membrane PTPase as a consequence of the effects
      of a cytosolic inactivator. Cytosol obtained from stimulated neutrophils
      possessed substantially reduced levels of this PTPase inactivator. We conclude
      that activity of the catalytic component of membrane PTPase in circulating
      neutrophils is regulated by a cytosolic inactivator. Upon stimulation, intact
      CD45 PTPase is incorporated into the plasma membrane by a process that requires
      tyrosine phosphorylation. As a result of inhibition of the cytosolic inactivator,
      the translocated PTPase expresses full activity, thereby amplifying the potential
      regulatory influence of the enzyme on the cells' functional response.

PMID- 8547662
TI  - Distinct temporal patterns of defensin mRNA regulation during drug-induced
      differentiation of human myeloid leukemia cells.
AB  - Defensins are microbicidal peptides and the principal constituents of neutrophil
      primary granules. They are presumed to play a prominent role in innate host
      defenses. We examined defensin mRNA levels during drug-induced differentiation of
      the promyelocytic leukemia cell line, HL-60. Transcription was restricted to
      promyelocyte, myelocyte, and very early metamyelocyte stages of the granulocytic
      pathway. Complete downregulation occurred during late granulocytic maturation or
      early during phorbol ester-promoted differentiation along the monocyte/macrophage
      lineage. Retinoic acid (RA) was the strongest inducer of defensin mRNA
      accumulation, even at doses too low to effect morphologic changes; the initial
      (first 48 hours), gradual increase resulted from transcriptional activation and
      was enhanced by granulocyte colony-stimulating factor. In contrast, addition of
      hybrid polar compounds led to a transient, drug-specific downregulation within
      the same time period, apparently by means of selectively induced, biphasic
      degradation of transcripts. Subsequent increase in transcript levels was faster
      and more pronounced with hexamethylene bisacetamide, relative to dimethyl
      sulfoxide (DMSO). DMSO-promoted effects were strikingly different in serum-free
      medium or in the presence of the tyrosine kinase inhibitor, genistein. Under
      these conditions, and although differentiation was unaffected, early defensin
      mRNA downregulation was final. The effect did not occur with RA and expression of
      other myeloid-specific genes was also unchanged. Addition of selected cytokines
      caused a similar "dip," only at earlier times and uncoupled from differentiation.
      Tumor necrosis factor-alpha markedly induced defensin levels after 2 days in
      previously untreated HL-60 cells, but inhibited expression in RA-differentiated
      cells. These results begin to detail a complex regulation of defensin mRNA
      synthesis with both spatial and temporal control elements, and a unique
      modulation by chemical agents, cytokines, and serum-factors.

PMID- 8547663
TI  - Type IV collagen-binding proteins of neutrophils: possible involvement of L
      selectin in the neutrophil binding to type IV collagen.
AB  - To isolate type IV collagen-binding proteins, 125I-labeled human-neutrophil
      extracts were chromatographed on a type IV collagen-Sepharose column. The
      affinity chromatography-separated fraction contained the four radioactive
      proteins with apparent molecular masses of 28, 49, 67, and 95 kD on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Western blot analysis
      indicated that the 95-kD proteins contained both L-selectin and nonspecific cross
      reacting antigen 90 (NCA90), and that the 67-kD protein was the 67-kD
      elastin/laminin-binding protein (67BP). The data obtained with the type IV
      collagen-affinity chromatography and the immunoaffinity chromatographies using
      anti-L-selectin and anti-NCA90 monoclonal antibodies (MoAbs) have shown that L
      selectin is closely associated with 67BP and the 49-kD protein, and that NCA90 is
      associated with 67BP, the 28-kD and 49-kD proteins. Among these binding proteins,
      sialic acid residues were contained in 67BP, L-selectin, and NCA90, but not in
      the 28-kD and 49-kD proteins. Sialidase treatment completely abolished both the
      binding affinity of the type IV collagen-binding proteins to type IV collagen and
      the neutrophil adherence to type IV collagen-coated plastic. Thus, the sialic
      acid residues of 67BP, L-selectin, and NCA90 seem to be important for the binding
      of neutrophils to type IV collagen. Furthermore, L-selectin IgG chimeric protein
      directly bound to type IV collagen-Sepharose column, and anti-L-selectin MoAb
      DREG56 inhibited the neutrophil adherence to type IV collagen-coated plastic by
      51%. These observations suggest that L-selectin likely plays a role in the
      neutrophil binding to type IV collagen, although neutrophils have several kinds
      of adhesion molecules for type IV collagen such as L-selectin, NCA90, 67BP, and
      the 28-kD and 49-kD proteins.

PMID- 8547664
TI  - Differential cytokine expression in human blood monocyte subpopulations: a
      polymerase chain reaction analysis.
AB  - The subpopulation of strongly CD14-positive (CD14++) monocytes and monocytes
      coexpressing the CD16 antigen and low levels of CD14 (CD14+/CD16+ cells) were
      isolated by fluorescence-activated cell sorting (FACS) followed by stimulation
      with lipopolysaccharide (LPS) at 1 micrograms/mL. Polymerase chain reaction (PCR)
      after reverse transcription of isolated mRNA (RT-PCR) revealed similar levels of
      tumor necrosis factor (TNF) transcripts in both subpopulations. By contrast,
      transcripts for interleukin-10 (IL-10) were only detectable in CD14++ monocytes,
      whereas CD14+/CD16+ cells produced no detectable IL-10 transcripts after 4 hours.
      Only after 16 hours of LPS stimulation was a low level of IL-10 transcripts
      discernible in CD14+/CD16+ monocytes. The same pattern was seen at the protein
      level in that TNF in LPS-stimulated supernatants was comparable for both
      subpopulations, whereas IL-10 was detected in CD14++ monocytes but not in
      CD14+/CD16+ cells. To avoid interference of cell activation by CD14 and CD16
      antibodies, cells were also isolated based on the high and low level of CD33
      antigen expression. Again, weakly CD33-positive cells, which comprise the
      CD14+/CD16+ cells, showed no or only minimal IL-10 mRNA. When comparing blood
      monocyte subpopulations with alveolar macrophages (AM), AM showed high levels of
      LPS-stimulated TNF, whereas IL-10 transcripts were undetectable. Our data show
      that CD14+/CD16+ blood monocytes produce high levels of proinflammatory cytokines
      like TNF, whereas the anti-inflammatory IL-10 is low or absent, a pattern similar
      to what is seen in AM.

PMID- 8547665
TI  - Identification of a novel exon and spliced form of Duffy mRNA that is the
      predominant transcript in both erythroid and postcapillary venule endothelium.
AB  - The Duffy gene has been shown not to be split by introns, even in its 5'
      untranslated region, and to be expressed not only in erythroid but in
      postcapillary venule endothelium of almost every organ in the body. To further
      investigate the transcriptional start position in erythroid and postcapillary
      venule endothelium, we performed 5'-rapid amplification of cDNA ends (5'-RACE).
      While every positive clone of 5'-RACE encoded the identical sequence of
      previously identified cDNA downstream from nucleotide 203, the upstream sequences
      were different. The upstream sequences corresponded to the sequence from
      nucleotide -279 to -308/-357 in erythroblasts and from -279 to -355/-383 in lung
      and were regarded as comprising a novel exon. This novel exon encoded seven
      residues initiated with a methionine, linked to nucleotide 203 in-frame and in
      agreement with the GT-AG splicing rule. The major erythroid transcriptional start
      position was identified in human erythroleukemia cells by primer extension and in
      bone marrow by ribonuclease protection analysis at 34 bases upstream from the
      first ATG codon. Distinctively, in lung and kidney, the transcription was started
      at 82 bases upstream from the ATG. Both Northern blotting and reverse
      transcription-polymerase chain reaction followed by Southern analysis indicated a
      predominance of the novel spliced form of mRNA of about 50- to 200-fold comparing
      with the unspliced form, in every studied organ and erythroid lineage cells. The
      spliced form of cDNA has been transfected into a human erythroleukemic cell line,
      K562, and the expressed protein reacted with Duffy-specific murine monoclonal
      antibody Fy6. These studies indicate that the product from the spliced form of
      mRNA is the major product of the Duffy gene in the erythroid lineage and
      postcapillary venule endothelium.

PMID- 8547666
TI  - Mutator phenotype in a subset of chronic lymphocytic leukemia.
AB  - The replication error phenotype (RER+), characterized by widespread
      microsatellite instability, is an important feature of tumors from patients with
      hereditary nonpolyposis colorectal carcinoma (HNPCC). This widespread instability
      affects repeat tracts of all lengths and is usually attributed to mutations of
      critical mismatch repair genes. Recently, several reports described occasional
      microsatellite alterations in tumors not associated with HNPCC. However, a true
      mutator phenotype (RER+) is very rare outside of HNPCC-associated malignancies.
      We examined 29 cases of chronic lymphocytic leukemia (CLL), the most common
      leukemia in the Western world for evidence of microsatellite instability. We
      identified a mutator phenotype in (2/29) 7% of the cases studied. These data
      suggest that the mismatch repair pathway may be altered in at least a subset of
      patients with CLL.

PMID- 8547667
TI  - Malignancies after marrow transplantation for aplastic anemia and fanconi anemia:
      a joint Seattle and Paris analysis of results in 700 patients.
AB  - Risk factors for the development of a new (secondary) malignancy after marrow
      transplantation are still incompletely defined. In the present study, we analyzed
      results in 700 patients with severe aplastic anemia treated with allogeneic
      marrow transplantation at the Fred Hutchinson Cancer Research Center in Seattle,
      WA, or at the Hopital St Louis in Paris, France. Twenty-three patients developed
      a malignancy 1.4 to 221 months (median, 91 months) after transplantation for a
      Kaplan-Meier estimate of 14% (95% confidence interval, 4% to 24%) at 20 years.
      Five cases were lymphoid malignancies (two acute lymphoblastic leukemias and
      three lymphoproliferative disorders) occurring 1.4 to 14.6 months (median, 3
      months) posttransplant, and 18 were solid tumors (17 squamous cell and one
      mucoepidermoid carcinoma) presenting 30 to 221 months (median, 99 months)
      posttransplant. Thus, the hazard for lymphoid malignancies declined rapidly
      posttransplant, while the hazard for solid tumors increased progressively with
      time posttransplant. Risk factors for solid tumors identified in univariable
      analysis included the underlying diagnosis of Fanconi anemia (P = .0002),
      azathioprine therapy for chronic graft-versus-host disease (GVHD) (P < .0001),
      irradiation (total body or thoracoabdominal) as part of the conditioning regimen
      (P = .0002), chronic GVHD (P = .0099), acute GVHD (P = .0135), and male sex (P =
      .0499). In multivariable, stepwise proportional hazards models, azathioprine
      therapy (P < .0001) and the diagnosis of Fanconi anemia (P < .0001) were
      significant factors for all patients. Irradiation was a significant factor (P =
      .004) only if the time-dependent variable azathioprine was not included in the
      analysis. If only non-Fanconi patients were considered, azathioprine (P = .0043),
      age (P = .025), and irradiation (P = .042) were significant factors. Results in
      patients with Fanconi anemia and malignancies other than solid tumors were not
      subjected to an analysis because of the small number of events. It is of note,
      however, that no case of myeloproliferative disorder was observed. In summary,
      the highest risk of developing a solid tumor was associated with the diagnosis of
      Fanconi anemia. Better prevention of GVHD or omission of azathioprine as GVHD
      therapy (or both) may reduce the risk of late tumor development. Similarly,
      nonirradiation conditioning regimens may reduce the tumor risk, at least in
      patients without Fanconi anemia. Interactions between potential risk factors are
      complex, and further observation and additional analyses will be of interest.

PMID- 8547668
TI  - Use of a lethally irradiated major histocompatibility complex nonrestricted
      cytotoxic T-cell line for effective purging of marrows containing lysis-sensitive
      or -resistant leukemic targets.
AB  - Improved marrow purging protocols are needed in autologous bone marrow
      transplantation (BMT) to achieve complete eradication of minimal residual
      disease. This study investigates the potential of a human major
      histocompatibility complex (MHC) nonrestricted killer T-cell line (TALL-104) as a
      new marrow purging agent in a clinical setting. TALL-104 cells can be irradiated
      without losing cytotoxic activity against tumor targets in vitro. In vivo, the
      irradiated killers can be adoptively transferred into immunodeficient and
      immunocompetent leukemia-bearing mice, and reverse their disease even in advanced
      stages. The present study shows that gamma-irradiated TALL-104 cells, cultured
      for 18 hours with marrows from healthy donors, do not impair the viability and
      long-term growth of committed and pluripotent hematopoietic progenitors. However,
      as determined by polymerase chain reaction (PCR) and colony assays, TALL-104
      cells could completely purge marrows containing up to 50% lysis-susceptible
      myelomonocytic leukemia cells (U937). When marrows were admixed with a pre-B
      leukemia cell line (ALL-1), which is fairly resistant to TALL-104 cell lysis in
      longterm 51Cr-release assays but can be totally growth inhibited by TALL-104
      cells in proliferation assays, residual ALL-1 cells were detectable by PCR after
      TALL-104 purging. However, importantly, these PCR+ marrows were devoid of
      tumorigenic activity when transplanted into the human hematopoietic
      microenvironment of human severe combined immunodeficient (SCID) chimeras. These
      data indicate the strong potential of the TALL-104 cell line in future marrow
      purging strategies against lysis-susceptible and -resistant leukemias.

PMID- 8547669
TI  - Activation and increased expression of adhesion molecules on peripheral blood
      lymphocytes is a mechanism for the immediate lymphocytopenia after administration
      of OKT3.
AB  - We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the
      isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of
      virtually all circulating T lymphocytes. We hypothesize that upregulation of
      adhesion molecules on the lymphocyte membrane contributes to this effect.
      However, this hypothesis is difficult to test, because of the inherent
      lymphocytopenia and/or shifts in lymphocyte populations between intra and extra
      vascular compartments. Therefore, studies in vitro were performed, as well.
      Analysis of peripheral blood lymphocytes isolated at several times after addition
      of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase
      in the proportion of T cells expressing NKI-L16, an activation epitope on
      CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel
      experiments, a transiently increased adhesion of T cells to endothelial cell
      monolayers was observed. This adhesion could be completely blocked by anti-CD18
      or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody.
      Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well
      as increased expression of CD11b/CD18 on T lymphocytes, may result in increased
      adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2
      on vascular endothelium. This phenomenon may, at least, partly explain the
      rapidly occurring peripheral lymphocytopenia observed in vivo.

PMID- 8547670
TI  - Lymphoma classification proposal.

PMID- 8547671
TI  - Expression of Thy-1 antigen (CDw90) on adult acute leukemia blast cells.

PMID- 8547672
TI  - Kaposi sarcoma-associated herpes-like virus (human herpesvirus type 8) DNA
      sequences in multicentric Castleman's disease: is there any relevant association
      in non-human immunodeficiency virus-infected patients?

PMID- 8547673
TI  - Atlas of blood disease on the internet.

PMID- 8547674
TI  - Biological profile of 23 cases of minimally differentiated acute myeloid leukemia
      (AML-M0) and its clinical implications.

PMID- 8547675
TI  - A bicistronic retrovirus vector containing a picornavirus internal ribosome entry
      site allows for correction of X-linked CGD by selection for MDR1 expression.
AB  - Chronic granulomatous disease (CGD) is an inherited hematologic disorder
      involving failure of phagocytic cell oxidase to produce superoxide (O2-.),
      resulting in recurrent infections. The success of retrovirus gene therapy for
      hematopoietic diseases will be limited both by the efficiency of ex vivo
      transduction of target cells and by the ability of corrected cells to replace
      uncorrected cells in vivo. Using MFG-based retrovirus vectors containing oxidase
      genes, we have previously demonstrated in vitro correction of CGD, but
      transduction rates were low. In the present study we explore a strategy for
      providing a selective growth advantage to transduced cells, while retaining the
      single promoter feature of MFG responsible for high virus titer and enhanced
      protein production. We constructed a bicistronic retrovirus producing a single
      mRNA encoding both the therapeutic gene for the X-linked form of CGD (X-CGD),
      gp91phox, and the selectable human multidrug resistance gene, MDR1 linked
      together by the encephalomyocarditis virus internal ribosome entry site (IRES).
      As a control we constructed a bicistronic vector with the polio virus IRES
      element and using the bacterial neomycin resistance gene (neor) as the selective
      element. In Epstein-Barr virus transformed B (EBV-B) cells from an X-CGD patient,
      a tissue culture model of CGD, we show correction of the CGD defect and complete
      normalization of the cell population using either of these vectors and
      appropriate selection (vincristine for MDR1 and G418 for neor). Using a
      chemiluminescence assay of O2-. production, populations of cells transduced with
      either vector demonstrated initial correction levels of from less than 0.1% up to
      2.7% of normal EBV-B cell oxidase activity. With either construct, cell growth
      under appropriate selection enriched the population of transduced cells,
      resulting in correction of X-CGD EBV-B cells to a level of O2-. production
      equalling or exceeding that of normal EBV-B cells. These studies show that a
      therapeutic gene can be linked to a resistance gene by an IRES element, allowing
      for selective enrichment of cells expressing the therapeutic gene. Furthermore,
      the use of MDR1 as a selective element in our studies validates an important
      approach to gene therapy that could allow in vivo selection and is generalizable
      to a number of therapeutic settings.

PMID- 8547676
TI  - Allogeneic marrow transplantation for refractory anemia: a comparison of two
      preparative regimens and analysis of prognostic factors.
AB  - From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and
      cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA)
      undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation.
      Nineteen patients survive disease free (63% 3-year actuarial disease-free
      survival [DFS]) and no patient relapsed. These results were compared to those of
      38 historical controls with RA treated with cyclophosphamide and total body
      irradiation, of whom 22 are disease-free survivors and 1 relapsed. After
      correcting for significant variables between the two treatment groups, we found
      no statistically significant difference in outcome based on preparative regimen.
      Combining data from these 68 patients plus 2 additional patients with RA treated
      before 1993 with busulfan and cyclophosphamide, we identified four variables
      independently associated with improved survival: younger age, shorter disease
      duration, lower neutrophil count pretransplant, and lower hematocrit
      pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3
      year actuarial DFS and 26 patients receiving unrelated or mismatched related
      donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not
      appear to be any significant difference in outcome based on preparative regimen
      in this patient population. In addition, allogeneic bone marrow transplantation
      may be a reasonable approach to therapy of RA early after diagnosis. However,
      whether early intervention with transplantation prolongs survival over that
      expected without transplantation cannot be ascertained with certainty from
      available data.

PMID- 8547677
TI  - Human cytomegalovirus increases constitutive production of interleukin-6 and
      leukemia inhibitory factor by bone marrow stromal cells.
AB  - Human cytomegalovirus (CMV) infection is often associated with myelosuppression
      and acute inflammatory reaction in immunocompromised patients. We have previously
      documented that CMV exposure of bone marrow (BM) stromal cells reduces the
      capacity of these cells to support hematopoiesis because of a decreased
      production of colony-stimulating factors. This study examines the potential role
      of CMV on constitutive and lipopolysaccharide (LPS)-stimulated production of
      cytokines involved in inflammatory reaction, interleukin-6 (IL-6) and leukemia
      inhibitory factor (LIF) by BM stromal cells. The release of IL-6 was already
      detectable 2 hours post CMV-infection (2.5-fold increase in production) and the
      cumulative production of IL-6 after 5 days of infection was 23 +/- 1.2 ng/mL
      (ninefold increase in production). CMV was also able to induce a time-dependent
      production of LIF that was maximal 8 hours after CMV infection (2.5-fold increase
      in production). Concomitantly, there was no detectable release of granulocyte
      colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) by CMV
      infected stromal cells. The similar IL-6 and LIF production in the presence of
      polymyxin B ruled out the possibility that this increase could be caused by
      contamination of the viral stock by endotoxin. In addition, ultraviolet
      inactivated virus behaved similarly to live virus and caused the release of IL-6
      and LIF. However, heat-inactivated CMV was unable to induce IL-6 and LIF
      secretion by BM stromal cells. The production of IL-6 and LIF was also evaluated
      after stimulation by LPS. After 5 days of CMV exposure, the LPS-stimulated
      production of IL-6 and LIF was significantly lower than uninfected controls. This
      LPS-induced release of cytokine production was found to be dependent of viral
      replication. The experiments have shown that CMV is a potent inducer of IL-6 and
      LIF with differential effect on constitutive and LPS-stimulated cytokine
      production by stromal cells; we suggest that CMV induction of IL-6 and LIF during
      the first hours of infection could play a role in CMV-induced inflammatory
      reaction. Moreover, our results show that human CMV can disturb the balanced
      cytokine network involved in the regulation of hematopoiesis.

PMID- 8547678
TI  - Aorta-associated CD34+ hematopoietic cells in the early human embryo.
AB  - Hematopoiesis is established from circulating blood stem cells that seed the
      embryonic rudiments of blood-forming tissues, a basic notion in developmental
      hematology. However, the assumption that these stem cells originate from the
      extraembryonic mesoderm, where primitive hematopoiesis is initiated by intrinsic
      precursors, has been reconsidered after analysis of blood cell development in
      avian embryo chimeras: yolk-sac-derived stem cells do not contribute
      significantly to the definitive blood system, whose first forerunners develop
      independently along the ventral aspect of the embryonic aorta. Recently, the
      homologous intraembryonic tissues of the mouse have been submitted to sensitive
      in vivo and in vitro assays, which showed that they also harbor multipotential
      hematopoietic stem cells. We have now identified a dense population of
      hematogenous cells, marked by the surface expression of the CD34 glycoprotein,
      associated with the ventral endothelium of the aorta in the 5-week human embryo.
      Therefore, we extend to the human species the growing evidence that
      intraembryonic hematopoietic cells developing independently of the yolk sac might
      be the real stem of the whole blood system.

PMID- 8547679
TI  - Adhesion receptors on bone marrow stromal cells: in vivo expression of vascular
      cell adhesion molecule-1 by reticular cells and sinusoidal endothelium in normal
      and gamma-irradiated mice.
AB  - Cell adhesion molecules (CAMs) play a key role in interactions between stromal
      and hematopoietic cells in bone marrow (BM) and in cell traffic through vascular
      endothelium. To examine the identity of CAMs involved in these processes in mouse
      BM, we have investigated the in vivo expression of vascular cell adhesion
      molecule-1 (VCAM-1) and its counter-receptor, very late antigen-4 (VLA-4).
      Radioiodinated monoclonal antibodies (MoAbs) detecting VLA-4 and VCAM-1 were
      injected intravenously. Antibody binding was detected in BM by light and electron
      microscope radioautography. VCAM-1 labeling was restricted to stromal reticular
      cells and endothelial cells lining BM sinusoids. VCAM-1+ reticular cells formed
      patchy concentrations, especially in subosteal regions, associated with lymphoid,
      granulocytic, and erythroid cells. After gamma-irradiation to deplete
      hematopoietic cells, reticular cells and endothelial cells all showed VCAM-1
      labeling in apparently increased intensity. VLA-4 labeling was shown by
      undifferentiated blast cells and lymphohematopoietic cells both in BM cell
      suspensions and in vivo, especially at reticular cell contact points. The results
      demonstrate that VCAM-1 is expressed in vivo by certain BM reticular cells,
      suggesting that the molecule mediates adhesion to multiple lineages of
      lymphohematopoietic cells. The finding that VCAM-1 is also expressed
      constitutively by BM sinusoidal endothelium, unlike its inductive expression by
      endothelia elsewhere, suggests that VCAM-1 and VLA-4 may be involved in
      regulating the normal cell traffic between BM and the blood stream.

PMID- 8547680
TI  - Monoclonal antibody 7G3 recognizes the N-terminal domain of the human interleukin
      3 (IL-3) receptor alpha-chain and functions as a specific IL-3 receptor
      antagonist.
AB  - The human interleukin-3 receptor (IL-3R) is expressed on myeloid, lymphoid, and
      vascular endothelial cells, where it transduces IL-3-dependent signals leading to
      cell activation. Although IL-3R activation may play a role in hematopoiesis and
      immunity, its aberrant expression or excessive stimulation may contribute to
      pathologic conditions such as leukemia, lymphoma, and allergic reactions. We
      describe here the generation and characterization of a monoclonal antibody
      (MoAb), 7G3, which specifically binds to the IL-3R alpha-chain and completely
      abolishes its function. MoAb 7G3 immunoprecipitated and recognized in Western
      blots the IL-3R alpha-chain expressed by transfected cells and bound to primary
      cells expressing IL-3R alpha. MoAb 7G3 bound the IL-3R alpha-chain with a kd of
      900 pmol/L and inhibited 125I-IL-3 binding to high- and low-affinity receptors in
      a dose-dependent manner. Conversely, IL-3 but not granulocyte-macrophage colony
      stimulating factor (GM-CSF) inhibited 125I-7G3 binding to high- and low-affinity
      IL-3Rs, indicating that MoAb 7G3 and IL-3 bind to common or adjacent sites. In
      keeping with the inhibition of IL-3 binding, MoAb 7G3 antagonized IL-3 biologic
      activities, namely stimulation of TF-1 cell proliferation, basophil histamine
      release, and IL-6 and IL-8 secretion from human endothelial cells. Two other anti
      IL-3R alpha-chain MoAbs failed to inhibit IL-3 binding or function. Epitope
      mapping experiments using truncated IL-3R alpha-chain mutants and IL-3R alpha/GM
      CSFR alpha chimeras revealed that 31 amino acids in the N-terminus of IL-3R alpha
      were required for MoAb 7G3 binding. MoAb 7G3 may be of clinical significance for
      antagonizing IL-3 in pathologic conditions such as some myeloid leukemias,
      follicular B-cell lymphoma, and allergy. Furthermore, these results implicate the
      N-terminal domain of IL-3R alpha in IL-3 binding. Since this domain is unique to
      the IL-3/GM-CSF/IL-5 receptor subfamily, it may represent a novel and common
      binding feature in these receptors.

PMID- 8547681
TI  - Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic stem
      cells and B cells.
AB  - A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains
      immunoglobulin-like loops and epidermal growth factor [EGF] homology domains), is
      expressed in vascular endothelial and hematopoietic cells. We generated
      monoclonal antibodies (MoAbs) against the extracellular domain of TIE and a
      polyclonal antibody against the TIE carboxyterminus and used them to analyze
      expression of TIE in hematopoietic cells. Western blotting detected two forms of
      TIE protein with a molecular mass of 135 and 130 kD in hematopoietic and
      endothelial cells. Northern blotting analysis revealed that TIE was expressed
      preferentially in undifferentiated cell lines, especially when megakaryocytic,
      but not erythroid differentiation was induced. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) showed that TIE was predominantly expressed in the human
      hematopoietic progenitor fraction, CD34+ cells. Fluorescence-activated cell
      sorting (FACS) showed that 42% of CD34+ and 17% of KIT-positive (KIT+) cells were
      TIE-positive (TIE+). The majority (81%) of the primitive hematopoietic stem
      cells, CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term
      culture-initiating cells (LTC-IC) showed that the TIE+ fraction contained more
      primitive cells than the TIE- fraction. Some TIE+ cells were in the CD34-
      fraction, which were CD19+ and CD20+ (B cells). These findings indicate that TIE
      has a unique spectrum of expression in primitive hematopoietic stem cells and B
      cells. Although its ligand has not been identified, TIE and its ligand may
      establish a novel regulatory pathway not only in early hematopoiesis, but also in
      the differentiation and/or proliferation of B cells.

PMID- 8547682
TI  - Outbreaks of gastroenteritis due to Norwalk-like virus in two long-term care
      facilities for the elderly.
AB  - In February 1993, outbreaks of gastroenteritis due to Norwalk-like viruses
      occurred simultaneously among the elderly residents of two long-term care
      facilities. Facility A instituted infection control measures that included
      increased surveillance, reinforcement of handwashing, keeping symptomatic
      residents in their rooms and relieving symptomatic staff of their work duties
      until 48 h after resolution of their symptoms. Facility B instituted a more
      stringent set of control measures that included all those implemented by facility
      A plus the following: staff from affected units were not permitted to work on
      other units, affected units were closed to new admissions, enteric precautions
      were instituted for ill residents, residents were restricted to their own units
      and education was provided to staff and residents about gastroenteritis. Facility
      A had an attack rate of 9%; the attack rate for facility B was 11% (P = 0.38).
      The duration of the outbreak was 29 days in facility A and 24 days in facility B.
      The impact these infection control measures had on the course of the outbreaks is
      difficult to determine. However, it is doubtful that the more stringent measures
      implemented at facility B had any greater effect on the course of the outbreak. A
      better understanding of the precise mechanisms of viral transmission is required
      in order to determine the most appropriate control measures for gastroenteritis
      due to Norwalk-like viruses in long term care facilities.

PMID- 8547683
TI  - Attitudes and beliefs of Canadian infection control decision-makers towards
      'borderline' methicillin-resistant Staphylococcus aureus.
AB  - 'Borderline' methicillin-resistant Staphylococcus aureus (MRSA) strains are
      inhibited by drug concentrations of 2 to 8 micrograms/mL. This type of resistance
      is usually mediated by 'hyper beta-lactamase' production which is detectable in
      vitro by susceptibility to combinations of a beta-lactam and a beta-lactamase
      inhibitor (ie, amoxicillin and clavulanic acid). A survey of Canadian infection
      control experts was performed to assess the knowledge, attitudes and beliefs
      regarding the containment requirements for borderline MRSA strains in acute
      health care facilities. Twenty-three of 38 Canadian infection control experts
      (61%) (members of the Canadian Hospital Epidemiology Committee [CHEC] or the
      Society for Healthcare Epidemiology of American [SHEA]) returned a questionnaire
      about a fictional patient with a postoperative wound infection with such a
      strain. Eleven respondents (48%) considered the isolate as an MRSA, 11 did not
      and one was unsure. All who did not believe the strain to be MRSA would not have
      isolated or cohorted the patient. Four in the latter group would have isolated
      the patient if he or she were on a neurosurgery or cardiovascular surgery unit,
      indicating a desire to restrict spread of this isolate on those units. Seven of
      the 12 individuals who had managed at least one patient with a borderline MRSA
      did not advocate patient isolation or cohorting, and five did. This survey has
      supported the belief that there are discrepancies among infection control
      decision-makers in Canada regarding the approach, precautions and therapy of
      patients infected with borderline strains of MRSA. Further data on virulence of
      and effective therapy for these isolates are needed to assess whether the
      additional cost is warranted in controlling the nosocomial spread of these
      isolates.

PMID- 8547684
TI  - Disinfectant drugs regulation.
AB  - The legislative authority and framework for the regulation of disinfectant drugs
      is outlined. The tiered approach to regulation of these products, which includes
      premarket review mechanisms, is described. The specific efficacy and labelling
      requirements for these drugs are also described.

PMID- 8547685
TI  - Five ways to improve your LTC infection control program and outcomes.

PMID- 8547686
TI  - Reuse of single-use medical devices.

PMID- 8547687
TI  - [Health science and public health].

PMID- 8547688
TI  - [Comparison of behavioral and emotional problems related to school nonattendance
      in Japanese elementary and junior high school students].
AB  - An epidemiological survey was performed on 1,887 mothers of Japanese general
      elementary school children in the same school district as that for general junior
      high school students that was previously reported. The questionnaire consisted of
      two major parts; the former concerning school nonattendance problems from April
      to September in 1994, and the latter was a Japanese version of the Rutter
      parental questionnaire. The following findings were obtained: 1) About 12% of the
      children were absent from school for one day or more either without any
      justifiable reasons or due to a psychological reason. The rate of nonattendance
      did not differ significantly from the 13% figure for the junior high school
      students. 2) The percentage of children who missed more than 20% of scheduled
      days of school was 0.16% in this survey compared to the 0.65% for this entire
      school district, both of which surpassed the national figure of 0.13% (1993
      fiscal year) in the annual report of the Japanese Ministry of Education. 3) The
      distinction of truancy from school refusal in the elementary school children was
      made more sharply than in the junior high school students. 4) The percentage of
      children who scored thirteen or more, the cutoff point of the Rutter parental
      questionnaire, was 8.6%, which is a rather low frequency in comparison to former
      reports in and outside Japan. While items relating to neurosis showed little
      difference between sexes, antisocial scores were higher in boys similar in
      tendency to junior high school students. In addition, the rate of positive
      responses to the Rutter parental questionnaire items were higher in the
      elementary school children, although those items showed less specific relation to
      school nonattendance than in the junior high school students. 5) Those in the
      school nonattendance group (n = 222) did not differ significantly from the school
      attendance group (n = 1367) in demographic characteristics such as sex, family
      size, total number of children and birth order. However, school grade, mother's
      school background and father's job category were significantly different. In
      addition, Rutter scores as well as neurotic and antisocial scores were much
      higher in the school nonattendance group. 6) Rutter scores, especially neurotic
      scores showed a rather high correlation to the number of nonattendance days,
      although not as high in magnitude as in the junior high school students. The
      school nonattendance group was divided into three groups, neurotic, antisocial
      and mixed. A rather strong relation between school nonattendance rate and the
      neurotic group (n = 77), and a qualitative difference between neurotic group and
      antisocial group (n = 56) were seen similar to the junior high school students.

PMID- 8547689
TI  - [Distribution of medical expenditures for the elderly].
AB  - The distribution in medical service use by the elderly was examined by using data
      from medical fee claim records of the Medical System for the Elderly for one
      year. The following are among the main findings: More than 50 percent of the
      patients consumed less than 300,000 yen per year, and those patients whose annual
      medical expenditures were between 600,000 yen to 4,000,000 yen consumed 54
      percent of the total expenditures of the elderly. The top 10 percent of patients
      consumed 50 percent of medical expenditures, and top 1 percent consumed 10
      percent. Lorenz curves of medical expenditures for different regions were
      relatively similar despite the large differences in medical expenditures per
      patient. Medical expenditures per patient did not appear to be related to the
      concentration in distribution of expenditures, although the former was strongly
      related to the proportion of long-term hospitalized patients. After various
      measures to control the increase rate of medical expenditures in 1980's, public
      attention has shifted slowly to the quality of services provided and cost
      effectiveness of medical services. The concentration in distribution of medical
      expenditures was considered to be a meaningful approach to investigate the
      effectiveness of medical services.

PMID- 8547690
TI  - [Body density assessment utilizing skinfold thickness and age in Japanese men].
AB  - A study was conducted to investigate the validity of skinfold-based prediction
      equations for body density (g/ml) by Nagamine and Suzuki (1964), and to formulate
      more convenient and more useful equations for predicting body density from
      skinfold and age in men. Subjects of the study were 257 healthy men aged 19-60
      years in or near Nagasaki City. The regression equation for the dependent
      variable, body density, was determined by hydrostatic weighing. Independent
      variables included eight skinfolds, the sum of two skinfolds (triceps,
      subscapular), the sum of three skinfolds (triceps, subscapular, and abdominal),
      age, and body surface area. Skinfolds were measured with an Eiken-model skinfold
      caliper. Age (mean 33.1, range 19-60 yrs.), weight (mean 65.3, range 46.6-107.7
      kg), height (mean 168.8, range 152.3-185.4 cm), and body density (mean 1.05874,
      range 1.00860-1.09020 g/ml) were also recorded. Percent body fat was calculated
      using the formula by Brozek et al. and ranged from 6.1% to 38.9%. Multiple
      correlation coefficients (MR) and standard error (SE) of 10 regression equations
      (A-J) for predicting body density in men were obtained. The best-fitting and the
      most convenient prediction equation for body density was equation-E.: body
      density = 1.09556-0.00062 x sum of three skinfolds (mm)-0.00028 x age (MR = 0.815
      and SE = 0.0087 g/ml). The equation was cross-validated on a different sample of
      45 men. The correlation coefficient between predicted and hydrostatically
      determined body density was 0.781 (p < 0.001). Equation-E (Tahara's equation)
      appears to be useful in body density analysis particularly when the subjects are
      Japanese men, aged 18-50 yrs, with percent body fat 10 to 30%.

PMID- 8547691
TI  - [Educational needs of home health care nurses].
AB  - Because of the rapid growth and changes occurring in home health care, nurses
      have a need for acquiring additional education and nursing skills. Post-RN
      (registered nurse) education in home health care, however, has not been developed
      yet. The purpose of this study was to identify the significant educational needs
      of the home health care nurses in order to upgrade nursing skills. A survey was
      conducted of members of the nursing society for intractable-diseases and other
      home health nurses introduced by some of the members. The survey questionnaires
      were sent to 172 subjects and the response rate was 79.6%. Practical nurses and
      inactive nurses were excluded to leave 125 registered nurses who were subjects of
      this analysis. The major findings in this study were as follows: a) The mean age
      of the respondents was 42.1 years old. The average length of clinical nursing
      experience was 17.0 years. b) Among fifty home care nursing skills indicated
      higher implementation percentage than high-technology nursing skills. c) The
      personal care skills as well as high-technology nursing skills showed low
      difficulty, while interviewing and counseling skill and communication skill
      showed high difficulty. d) The respondents showed high educational needs for
      mastering high-technology nursing, communication and counseling skills. e)
      Clinical nursing experience of hospital service was found to be significantly
      useful means for the respondents to perform most of the home care nursing skills.
      Reference books were utilized as supplementary to the clinical experience. f)
      When asked about their desire for educational resources to provide high quality
      home health care nursing, approximately 80% responded that they wanted to obtain
      up-to-date information, and opportunities for clinical practice training courses.
      On the basis of our findings, the following skills could be crucial for the home
      health nurses and should be included in continuing educational programs;
      interviewing and counseling, interpersonal communication, high-technology home
      health care nursing, and independent decision-making.

PMID- 8547692
TI  - [Falls among the elderly living in a rural community--prevalence and
      circumstances of falls by season].
AB  - The purpose of the study is to assess the prevalence and circumstances of falls
      by season among the elderly living in a rural community. From 1992 to 1993 four
      interview surveys on falls were conducted every three months. Out of the total
      1,321 subjects aged 65 and over (male: 532, mean age: 73.2 yr, female: 789, mean
      age: 74.5 yr), 1,317 responded to the survey in summer, 1,306 in autumn, 1,236 in
      winter and 1,248 in spring. The prevalence of falls (the rate of subjects with
      falls) were 7.4% in summer, 5.9% in autumn, 6.5% in winter and 6.7% in spring.
      The seasonal variation was not statistically significant. In each season, there
      was no significant difference between genders. The prevalence in the older group
      aged 75 and over is higher than that in younger group aged 65-74 except in
      spring. As to the circumstances of falls, there were seasonal differences in the
      distribution of place, footwear and cause of falls. These differences may be due
      to the climate of the area.

PMID- 8547693
TI  - [Long-term analysis of hypertension in men by job type].
AB  - Health education intervention for hypertension require the assessment of
      hypertension. Risk factors for developing hypertension in Japanese workers were
      evaluated by the type of occupation: manager, office worker, salesperson, blue
      collar worker, and engineer. A cohort of 2,257 male subjects, aged 21 through 63
      years, who were normotensive, diastolic blood pressure less than 90 mm Hg and
      systolic blood pressure less than 140 mm Hg in the initial year, were followed
      for 15 years to observe the occurrence of hypertension. Hypertension was defined
      as a systolic blood pressure (SBP) of 160 mm Hg or higher and/or a diastolic
      blood pressure (DBP) of 95 mm Hg or higher, or the initiation of antihypertensive
      therapy. Eight risk factors related to hypertension (age, body mass index,
      cigarette smoking, job characteristic, alcohol consumption, stress, SBP, and DBP)
      were selected for analysis using Cox proportional hazards models. Stepwise model
      was utilized to incorporate risk factors for each type of occupation (p < 0.05).
      The following results were obtained: 1. The incidence of hypertension over 15
      year analysis was 29.3% for the total male subjects. 2. Each type of occupation
      had a different pattern of risk factors for hypertension. 3. Blood pressure at
      baseline showed a significant association in all types of occupation, indicating
      a stronger relationship with hypertension than other factors. 4. Stress and age
      were significantly associated in managers, salespersons, and blue-collar workers.
      5. Body mass index and alcohol consumption were significantly associated in
      salespersons. 6. Cigarette smoking was significant in managers and blue-collar
      workers, with the hazard ratio in managers being greater than 1 (1.66, 95%CI 1.06
      2.60) but less than 1 in blue-collar workers (0.31, 95%CI 0.15-0.67). 7. In all
      types of occupation, job characteristic failed to reach statistical significance.
      Work-site primary prevention of hypertension should be performed specifically
      considering type of occupation. Individual risk assessment and lifestyle
      modification are potentially important tools for health education in the work
      site and by applying this model to primary preventive care, appropriate
      preventive activities specific to an individual may be developed and provided.

PMID- 8547694
TI  - [Validity of photographical dietary assessment; a preliminary analysis].
AB  - We estimated nutritional intake from color photographs taken of meals with a 35
      mm camera, and compared them with the values calculated from the menu. Among 21
      meals examined, the coefficient of correlation between the values by the photo
      method and those from examining the menu was appreciably high; 0.842 in energy,
      0.828-0.931 in three major nutrients, and 0.745-0.940 in vitamins and minerals.
      The differences between the photo method and menu observation were 0-14.8% on
      average, and the coefficient of variation of the differences was 9.1-32.3%.
      Estimation of salt was, however, very poor, and the agreement was lower due to
      the cooking method used. Some differences were found among the dietitians in
      estimated values of several nutrients. The running cost was approximately 87-yen
      per meal, which may pose a problem for large-scale dietary surveys. Compared with
      the use of record, recall, and frequency questionnaire methods, the photo method
      was easily used by participants, especially those not used to cooking, and could
      be applied to eating out or for take-out food. Moreover, this method may provide
      not only quantitative data but also qualitative including eating atmosphere. When
      estimation is difficult due to the ingredients or recipe, combined use with
      record or recall methods can facilitate estimation. This photo method is thus
      considered to be a valid and feasible means of dietary assessment.

PMID- 8547695
TI  - [Legal aspects of health insurance claims and their potential use as a data
      source for epidemiological research].
AB  - Health insurance claims are legal documents for the purpose of billing health
      care cost and not intended for medical certification. They contain valuable
      public health data as well as sensitive personal information which must be kept
      confidential. Conflicts arise between the public interest and the privacy
      protection when public health researchers attempt to perform studies using health
      insurance claims. This article examines the legal aspects of health insurance
      claims and proposes legitimate procedures and forms for using claims data in
      public health research: researchers should act as "contractors" to perform survey
      under the auspices of insurers instead of requesting the "disclosure" of the
      personal information.

PMID- 8547696
TI  - Etiologies seem to be changing faster than the times!

PMID- 8547697
TI  - Ototoxicity and irradiation: additional etiologies of hearing loss in adults.
AB  - A brief review of the effects of the seven groups of substances and chemicals
      known to affect hearing and/or the vestibular system is followed by a more
      detailed discussion of cisplatin (cisplatinum). An illustrative case study is
      included that exemplifies a recent finding of some recovery of hearing following
      withdrawal of cisplatin chemotherapy. Some suggestions for reducing the potential
      for ototoxicity are also presented. The article continues with a discussion of
      the effects of irradiation on hearing and the ear and an illustrative case study.
      Included are some reported results from patients in the Ukraine who were exposed
      to excessive radiation as a result of the Chernobyl nuclear disaster. A
      discussion of the effects on the ear and the vestibular system caused by the
      interaction between chemotherapy and irradiation treatment is followed by the
      warning that, with the recent successes these treatments have had in the war
      against cancer, more patients with hearing loss triggered by these techniques
      will be seen in audiology clinics. These factors are now one of the newest and
      more frequent etiologic factors for hearing loss in adults in this decade.

PMID- 8547698
TI  - Human immunodeficiency virus and acquired immune deficiency syndrome AIDS-related
      hearing disorders.
AB  - After a brief discussion of the nature of the human immunodeficiency virus
      (HIV)/acquired immune deficiency syndrome (AIDS) disease process and its
      consequences, the article considers implications for the ear and hearing. One of
      the newest etiologic considerations for audiologists is pediatric autoimmune
      deficiency syndrome (PAIDS). Babies born to HIV-AIDS-positive mothers, and
      children who have acquired the disease, represent a new challenge to clinics.
      Symptoms, audiologic care, and management are considered.

PMID- 8547699
TI  - Risk factors for hearing disorders: epidemiologic evidence of change over time in
      the UK.
AB  - The prevalence** of all bilateral sensorineural hearing impairments of at least
      40 dB HL was assessed by a retrospective ascertainment study to be about 1.2
      children per 1000 births per annum, over the period 1983-1988. This prevalence
      was highly variable over year and region of the study. For all profound (at least
      95 dB HL) impairments, the prevalence was 1 in 2703 children per birth cohort.
      The contribution of acquired impairments and inter-region transfers after birth
      was not trivial, being over 25 percent for the profound impairments. The
      proportion of the bilateral moderately profoundly hearing impaired who might have
      been in the neonatal intensive care unit, have a family history of childhood
      deafness, or craniofacial anomaly recognizable prior to maternity discharge was
      64 percent. Changes in the relative distribution of the etiology of hearing
      impairment seem to have taken place since the EC 1969 birth cohort study. These
      changes should have considerable impact on the planning of services for hearing
      impaired children and child health surveillance in general.

PMID- 8547700
TI  - Recent changes in the etiology of hearing disorders: perinatal drug exposure.
AB  - In recent years, we have observed causes of congenital or early onset hearing
      disorders that had not been recognized or known to exist before. These include
      drugs passed to an as-yet unborn child. Principal among them is alcohol, but
      others, such as cocaine, are now also occupying our attention. This article
      reviews the effects of such exposure on the communication skills of children who
      had been exposed. It is not yet clear whether there are specifically auditory
      effects, nor is it clear whether the communicative effects are long lasting.

PMID- 8547701
TI  - Potential risk of hearing damage associated with exposure to highly amplified
      music.
AB  - The experience of highly amplified music listening is described from a
      psychoacoustic and phenomenologic standpoint in order to characterize both the
      estimated risk of hearing damage and the perception of such a risk. Exposure as
      attenders and as the result of a professional activity are examined separately.
      Data collected in discotheques are analyzed, showing that this type of music is
      characterized by (a) strong pulsations, the rate of which is approximately 2 Hz;
      (b) a narrow dynamic range; and (c) a sloping spectrum with maximum energy in the
      1/3-octave centered at 63 Hz. This spectrum is almost parallel to the free-field
      hearing threshold curve raised by 80 dB. Although temporary threshold shift is
      predictable for different durations of exposure to this type of sound, the long
      term risk of permanent threshold shift appears to be very slight for those who
      are regularly exposed to loud music. An anthropologic approach is proposed with a
      health education approach to the prevention of hearing loss resulting from
      amplified music listening.

PMID- 8547702
TI  - Factors causing hearing impairment: some perspectives from Europe.
AB  - This review concentrates on factors causing permanent hearing impairment in
      childhood, described in some European studies. The emphasis is on comparative
      studies, based on strict criteria and terminology upon which longitudinal changes
      in the pattern of factors causing hearing impairment can be demonstrated in well
      defined cohorts of children. The high proportion of 20-39 percent of unknown
      causes of permanent hearing impairment in childhood reflects a general lack of
      knowledge about causative factors and systematic etiologic evaluation within
      pediatric audiology. Future surveillance programs, including examination
      procedures directed towards causative factors, may see a reduction of the
      "unknown" category and ultimately may result in prevention of permanent hearing
      impairment in childhood. Some factors causing hearing impairment in adults are
      mentioned, including recent studies that show organic toxic solvents as a factor.
      As well, some controversial findings concerning the relationship between hearing
      impairment and endocrine disorders such as hypothyroidism and diabetes mellitus
      are briefly reported. It is concluded that future developments and research in
      the etiologic field within pediatric and adult audiology may contribute to the
      delineation of yet unknown damaging factors or reduction of the effect of factors
      causing hearing impairment--a disorder that ultimately results in adverse effects
      on the quality of life in all age groups.

PMID- 8547703
TI  - Acoustic neuroma.

PMID- 8547704
TI  - Neonatal ventilation and sensorineural hearing loss.

PMID- 8547705
TI  - Quantitative determination of antibody binding capacity (ABC) by flow cytometry.

PMID- 8547706
TI  - A standardized flow cytometry protocol for mobilized peripheral CD34+ cells
      estimation and collection for autotransplantation in cancer patients.

PMID- 8547707
TI  - Unexpected phenotypes and predominant TCR V gene usage in random selected
      subjects.
AB  - The presence of a subset of T lymphocytes with an irregular phenotype has been
      identified in the peripheral blood of 22 subjects, selected among more than 5000
      individuals evaluated for peripheral blood lymphocyte subset distribution as part
      of a routine procedure. By Southern Blot Analysis 13 out of 14 of the analysed
      samples presented additional non-germline bands, indicative of monoclonal or
      oligoclonal T cell expansions. Moreover, the cytometric analysis showed that 7
      out of 19 analysed samples were restricted for a subfamily of the TCR variable
      regions. Thus, lymphocyte subsets with phenotypic irregularities could represent
      the clonally driven expansion of otherwise normally subpopulations, which may be
      present in peripheral blood below the limit of detection of routine phenotypic
      analyses. Such clonal populations could exert a regulatory activity either on the
      pathogenetic mechanisms of the disease or in maintaining homeostasis in healthy
      people.

PMID- 8547708
TI  - CD4 enumeration in HIV infected individuals.
AB  - In the present study, two alternative methods for the enumeration of PB CD4+
      lymphocytes are compared with conventional flow cytometry (FCM): the TRAX CD4 tm
      enzyme immunoassay test kit and a new method using an internal biological
      standard (liophilized lymphocytes) for the direct enumeration of total PB CD4+ T
      cells. Both methods showed an overall high degree of correlation with
      conventional FCM. However, the TRAxCD4 tm enzyme immunoassay showed a significant
      overestimation of PB CD4+ T-cells that was not only due to monocyte-derived CD4
      molecules and the use of liophilized lymphocytes as an internal biological
      standard showed a low level of correlation for patients displaying low CD4
      counts.

PMID- 8547709
TI  - Detection of T cell CD4 epitopes in HIV-infected individuals.
AB  - HIV antigens can be detected in the circulation of HIV-infected patients and are
      associated with active virus production. Free virions and shedded gp120 bind CD4
      with high affinity. We have studied the expression of Leu3a and OKT4 epitopes on
      a CD4+ T cell line (HPB-ALL), pretreated with HIV rgp120, and on CD4+ pheripheral
      blood T lymphocytes of HIV-infected patients. The associated determination of
      these epitopes (the Leu3a mapping at the gp120 binding site of CD4 and the OKT4
      mapping at a site independent of gp120 binding) allowed to monitor binding of
      gp120 to surface CD4 and maintenance of CD4 expression. The comparison of MFI of
      gp120-treated versus untreated Leu3a+ HPB-ALL cells suggested that the Leu3a
      epitope was masked by treatment with 20 micrograms/ml rgp120, while with 1
      microgram/ml rgp120 masking was undetectable, although gp120 was bound to cells.
      The determination of the Leu3a and OKT4 epitopes in 105 HIV-infected individuals
      and in 50 normal controls, showed that the Leu3a epitope is detected equally well
      in HIV-infected and in normal subjects, provided the anti-Leu3a is used at
      saturation. Therefore the binding to epitopes distinct from the gp120-binding
      site does not seem to be a requisite for the selection of anti-CD4 mAbs for
      immunophenotyping. To optimize the detection of CD4 masking, a limiting amount of
      conjugated anti-Leu3a has to be used. Measurements of CD4 binding by gp120 in
      terms of gp120-free CD4 molecules, as detected by reactivity with anti-Leu3a, may
      be used to monitor disease progression in HIV-infected subjects.

PMID- 8547710
TI  - Flow cytometric analysis of cell function: cytosolic Ca++ modulation in human
      polymorphonuclear leukocytes and T lymphocytes.
AB  - Flow cytometry and fluo-3/AM have been used to track cytosolic Ca++ modulation in
      human polymorphonuclear leukocytes (PMN) and T lymphocytes. The chemotactic
      peptide N-formylmethionyl-phenylalanine (FMLP) but not the phorbol ester PMA
      induced cytosolic Ca++ modulation in PMN along with forward and side scatter
      modification. PMA inhibited FMLP activity when preincubated with PMN. T
      lymphocytes were antigen specific T cell clones and were stimulated with various
      amounts of diverse superantigens or PHA. Data show that superantigens can induce
      either activation or anergy depending on culture conditions. The biological
      significance of these data are discussed.

PMID- 8547711
TI  - Lymphocyte binding to K562 cells: effect of target cell irradiation and
      correlation with ICAM-1 and LFA-3 expression.
AB  - Tumor irradiation induces modifications in the interaction of surviving target
      cells with immune cells. This interaction is mediated by adhesion molecules,
      whose expression can be strongly altered by radiation treatment. Here the
      probably of K562 tumor cells for lymphocyte binding was studied after exposure of
      target cells to different doses of gamma-radiation. Results were correlated to
      the expression of ICAM-1 and LFA-3 adhesion molecules on target cells. Radiation
      treatment enhanced the expression of both ICAM-1 and LFA-3 on the surface of
      target cells in a dose and time of culture-dependent fashion, reaching a maximum
      24 hrs postirradiation, when also lymphocyte binding was increased. 10-30 Gy
      irradiation of K562 cells in vitro induces after 24 hrs, an up-regulation of ICAM
      1 and LFA-3 expression that, in turn, increase lymphocyte binding, making tumor
      cells more exposed to cytotoxic attack. The progressive morphological damage
      induced by radiation, documented by the scattering singlas in flow cytometry and
      by electron microscopy analysis of irradiated K562 cells, induced, particularly
      at delayed times of culture in high doses irradiated cells, alterations of the
      target cell surface that might prevent the correct interaction with immune cells.

PMID- 8547712
TI  - The blockage of the human transferrin receptor by a monoclonal antibody, EA.3,
      induces growth inhibition in leukemia cell lines.
AB  - In our program to produce monoclonal antibodies against hemopoietic functional
      antigens we have obtained an hybridoma cell line EA.3 reacting with human
      transferrin receptor. This monoclonal antibody is an IgM that displays "in vitro"
      antiproliferative activity against leukemic cells due to its competition with
      transferrin on the receptor. Cell cytotoxicity was demonstrated either with the
      blockage of BrdU incorporation in HL-60 cells and with leukemic CFU inhibition.
      In contrast, K562 cells were insensitive to the blockage of the transferrin
      receptor induced by this MAb.

PMID- 8547713
TI  - Negative signalling via the P58/NKR for HLA.C alleles.
AB  - Recent studies have demonstrated that the interaction between HLA class I alleles
      and specific NK receptors results in negative signals which inhibit NK-mediated
      cytotoxicity. Such NK receptors have been identified by GL183 and EB6 mAbs which
      recognize distinct members of a molecular family involved in the recognition of
      two groups of HLA.C alleles. Now we describe a new allospecific NK group (group
      0) which recognize all HLA.C alleles and we demonstrate that, on these clones,
      the p58 molecules EB6 and GL183 act independently to recognize Cw4 (and related
      alleles) and Cw3 (and related alleles) respectively. Finally we investigate
      whether the inhibitory signal mediated by the NK-receptor for HLA.C induce a
      temporary turn off on the cytolytic activity.

PMID- 8547714
TI  - Quality control in immunophenotyping: U.S. efforts to establish common
      methodology and their impact. American Society for Histocompatibility and
      Immunogenetics.
AB  - Several organizations in the United States have recently been involved in the
      quality assurance of immunophenotyping using flow cytometry. These activities
      include publication of guidelines for immunophenotyping, particularly in human
      immunodeficiency virus infection, performance evaluation and proficiency testing
      programs, and training and continuing education programs. Through questionnaires
      and results from performance evaluation programs, variability in test results has
      been decreasing the last few years, and more laboratories are beginning to use
      the same specimen processing and data analysis procedures.

PMID- 8547715
TI  - Circulating killer cells in women undergoing needle-directed excisional breast
      biopsy.
AB  - Needle-directed excisional breast biopsy (NDBB) is performed on many women having
      suspicious mammograms. Only a small subset of these women (approximately 20%)
      will be found to have breast cancer. The goal of this study was to test the
      hypothesis that presence (or absence) of circulating lymphocytes able to kill
      cultured breast cancer-derived cell lines would discriminate the subset of women
      with early forms of breast cancer from those with benign breast disease. The
      immune status of over 200 women undergoing NDBB was ascertained at the time of
      biopsy from a peripheral blood sample. Use of a standard surface
      immunophenotyping panel able to discriminate a variety of both natural killer
      cells and cytotoxic T lymphocytes revealed no significant differences when
      compared to a group of healthy volunteers or to the normal ranges established for
      our laboratory. Functional assays (cytotoxicity studies) were performed in a
      blinded fashion on peripheral blood lymphocytes from a subset (N = 31) of these
      women using a panel of target cell lines. Target cells included the NK sensitive
      K562; the NK resistant Daudi; and two breast cancer-derived cell lines, the
      hormone sensitive MCF7 and MDA-MB-435 which has been shown to metastasize in
      immunocompromised mice. No differences were apparent among the groups with
      respect to ability to kill either K562 or Daudi. All individuals undergoing NDBB
      had an enhanced ability to kill the breast cancer-derived cell lines compared to
      healthy donors. Individuals with breast cancer killed, on average, twice as many
      MCF7 cells as than did individuals with benign breast disease whereas both groups
      killed approximately three times as many MDA-MB-435 cells as did healthy donors.
      Further, a higher proportion of the women undergoing NDBB (2-3x) had relatively
      high cytotoxic ability directed against the breast cancer-derived lines than was
      found among healthy donors. These data expand earlier observations (Hamilton et
      al., 1988) that women with stage I breast cancer had elevated ability to kill
      MCF7 to include a substantial subset of all women with suspicious mammograms.

PMID- 8547716
TI  - Inhibition of NK binding to K562 cells induced by MAb saturation of adhesion
      molecules on target membrane.
AB  - Cell to cell interaction play a major role in the induction of a immune response.
      NK cells represent a special lymphoid subset which displays its cytotoxic
      function without the engagement of MHC system. In order to investigate the role
      of different adhesion molecules in the mechanism of binding of the NK cell to the
      classic tumor target K562 cell, we have employed different unclustered mAbs of
      the Adhesion session (5th "CD" Workshop, Boston 1993) mostly of the CAM (cell
      adhesion molecule) subpanel. After their reactivity characterization both on
      lymphocytes and K562 cells, those that demonstrate reactivity against the tumor
      target were tested in the binding assay. The target was pretreated with the
      monoclonal in order to block a possible reacting molecule for the effector. Then,
      after the incubation of lymphocytes with PE-labelled anti CD16 mAb, their ability
      to bind to the target was tested in flow. While the majority of the mAbs did not
      induce any significant change in the binding capacity of the NK subset, few of
      them did, and precisely anti-CD58 (LFA-3) and anti-CD54 (ICAM-1) which showed
      different level of inhibition, particularly drastic with S002, S083 and S100.
      Other mAbs, such as the S011 (anti-CD59), due to the presence of the PI-linked
      glycoprotein recognized on both target and effector membranes, and to its
      capacity to stimulate NK activity, produced a total binding of the NK population.
      The coincubation of targets with anti-CD54 and anti-CD58 allowed to reduce at the
      lowest level this function. This data seem to support the hypothesis of specific
      surface molecules involved in the binding process of the NK cell, after
      recognition of the target.

PMID- 8547717
TI  - Cytoskeletal oxidative changes lead to alterations of specific cell surface
      receptors.
AB  - Electron acceptors in biological systems, termed "oxidants", have been associated
      with numerous cytopathic conditions. In particular, oxygen-derived free radicals
      have been shown to induce various subcellular oxidative injuries which can lead
      to different types of pathologies. It has also been suggested that oxidative
      stress induced by xenobiotics can determine specific subcellular alterations in
      in vitro models. An oxidative imbalance in cells seems in fact to affect
      intracellular functions including the expression of some growth factor surface
      receptors. In this work, we observed a specific early alteration of the
      microfilament system and the microtubular network induced in K562 cells by
      oxidative stress. In particular, we hypothesize that oxidative imbalance could
      lead to an impairment of the expression of these receptors, such as transferrin
      receptors, via a modification of the cytoskeleton. This could represent a general
      mechanism by which a modification of receptor regulation can lead to cell aging,
      injury or death.

PMID- 8547718
TI  - William Budd and typhoid fever.

PMID- 8547719
TI  - The civil rights of Mary Mallon.

PMID- 8547720
TI  - Reassessing cancer mortality in Rhode Island, an old urban state.

PMID- 8547721
TI  - Review of Hodgkin's disease and lung cancer following non-Hodgkin's lymphoma in
      Rhode Island and review of the literature.

PMID- 8547722
TI  - Chemotherapy given for lung cancer causes incidental and long-term cure of fungal
      skin infection.

PMID- 8547723
TI  - Lumbar spinal stenosis: a review.
AB  - Lumbar spinal stenosis can usually be identified after a thorough history and
      physical examination. Most individuals with this condition are successfully
      treated by non-operative means. Invasive radiologic studies and surgery are
      reserved for those patients who fail to respond to conservative measures. In
      these select cases, predictably good results can be expected from lumbar
      decompression.

PMID- 8547724
TI  - AIDS in older patients: a problem of increasing concern.

PMID- 8547726
TI  - Prostate cancer in Rhode Island.

PMID- 8547725
TI  - Point of view: therapy with growth hormone.

PMID- 8547727
TI  - Update: prostate cancer screening.

PMID- 8547728
TI  - Thrombocytopenia in intensive care patients: a comprehensive analysis of risk
      factors in 314 patients.
AB  - OBJECTIVE: To define the incidence and severity of thrombocytopenia in a mixed
      medical-surgical population of critically ill patients and to examine factors
      that may be related to the development of thrombocytopenia. DESIGN: Retrospective
      chart review of 314 critically ill patients requiring at least 3 days of critical
      care. SETTING: A 17-bed combined medical-surgical intensive care unit (ICU) in a
      560-bed tertiary care community hospital. PATIENTS: Medical and surgical patients
      admitted to the ICU. INTERVENTIONS: All medical records over the duration of the
      ICU stay were reviewed. All scheduled medications, including dosage and
      start/stop dates, were recorded. All platelet counts, placement of pulmonary
      artery catheters, liver function test results, and admission serum creatinine
      concentrations were collected. MEASUREMENT AND MAIN RESULTS: Thrombocytopenia
      (platelet count less than 200 x 10(9)/L) was observed frequently, but rarely
      reached a severe stage (7 patients). No single diagnostic category was
      significantly associated with thrombocytopenia alone, although the combination of
      sepsis syndrome/septic shock and respiratory failure was strongly correlated (p <
      0.0001) with thrombocytopenia. Liver function abnormalities were correlated
      strongly with thrombocytopenia, and the majority of patients (5 of 7) with severe
      thrombocytopenia (less than 20 x 10(9)/L) were found to have concurrent severe
      alterations in liver function test results. Pulmonary artery catheter placement
      and heparin exposure were associated strongly with thrombocytopenia (p < 0.0001).
      Drug therapies that were correlated with thrombocytopenia included heparin and
      vancomycin (p < 0.05). Hemodynamic instability was correlated strongly with the
      presence and severity of thrombocytopenia. In a stepwise linear regression model,
      the admission platelet count accounted for the largest proportion of the variance
      (43%), followed by hemodynamic instability (8%) and the requirement for inotropic
      agents (2%). CONCLUSIONS: Thrombocytopenia in the critically ill occurs
      frequently, rarely reaches severely depressed concentrations, and primarily
      represents a manifestation of disease processes initiated prior to admission.
      Hemodynamic instability and/or heparin exposure appear to be the strongest
      identifiable correlates with thrombocytopenia. Although these may cause
      infrequent isolated cases, other specific drug causes of thrombocytopenia are not
      responsible for the majority of cases of thrombocytopenia in the critically ill.

PMID- 8547729
TI  - Carbamazepine pharmacokinetics in obese and lean subjects.
AB  - OBJECTIVE: To compare carbamazepine pharmacokinetic parameters between obese and
      lean subjects following the administration of a single 200-mg tablet. DESIGN:
      Single-dose intervention, open study. SETTING: Teaching university hospital.
      SUBJECTS: Eighteen obese (group A) otherwise healthy subjects, referred to the
      metabolic outpatient clinic, and 13 healthy lean (group B) volunteers. Inclusion
      criterion for the obese subjects was a body mass index (BMI = weight/height2) of
      more than 30 kg/m2. In the obese group, mean +/- SD total body weight (TBW), BMI,
      and percent of ideal body weight (IBW) were 111.4 +/- 19.9 kg, 38.8 +/- 6.0
      kg/m2, and 182.7% +/- 30.7%, respectively. These values were significantly
      greater than the respective values of 63.2 +/- 8.3 kg, 22.4 +/- 1.6 kg/m2, and
      105.8% +/- 5.8% obtained in the lean group (p < 0.001). INTERVENTION: Single-dose
      oral administration of carbamazepine 200-mg tablet (Teril, Taro, Israel).
      OUTCOMES: Carbamazepine elimination half-life (t1/2), apparent volume of
      distribution (Varea/F), and its oral clearance (Clpo/F) were derived from the
      drug concentration-time curves. RESULTS: Carbamazepine Varea/F and t1/2 were
      significantly greater in group A than in group B (98.4 +/- 26.9 vs. 60.7 +/- 8.5
      L, respectively, p < 0.001; and 59.4 +/- 14.7 vs. 31.0 +/- 5.0 h, respectively, p
      < 0.001), but its Clpo/F was reduced only slightly in obese as compared with lean
      subjects (19.8 +/- 5.2 vs. 23.0 +/- 4.6 mL/min, respectively, p = 0.07).
      Correction for IBW yielded similar results for Varea/F and t1/2, but Clpo/F per
      kg of IBW was significantly smaller in the obese than in the lean subjects (0.32
      +/- 0.07 vs. 0.39 +/- 0.06 mL/min/kg of IBW, respectively, p < 0.02). Linear
      correlations were observed between Varea/F and TBW for both group A (r = 0.92, p
      < 0.001) and group B (r = 0.77, p < 0.002). CONCLUSIONS: In comparison with lean
      subjects, carbamazepine Varea/F is significantly greater in obese subjects and
      its t1/2 is markedly prolonged. The minor nonsignificant effect of obesity on
      carbamazepine Clpo/F suggests that in obese subjects the carbamazepine daily dose
      should be based on IBW, not on TBW.

PMID- 8547730
TI  - Aerosolized beta 2-agonists do not induce bronchial hyperreactivity in healthy
      adults.
AB  - OBJECTIVE: To determine whether regular administration of beta 2-agonists could
      induce bronchial hyperreactivity in nonasthmatic volunteers. DESIGN: A
      prospective, randomized, double-blind, placebo-controlled, crossover clinical
      trial of 2 weeks therapy with a 2-week washout period between each treatment
      period. Treatments were albuterol or matching placebo as 2 inhalations 4 times
      daily. SUBJECTS: Ten healthy, nonsmoking women 27-37 years old. SETTING: General
      clinical research center of a tertiary care university hospital. MAIN OUTCOME
      MEASURES: Baseline spirometry and methacholine bronchoprovocation studies were
      performed immediately prior to, 12 hours following, and 1 and 2 weeks following
      each treatment period. RESULTS: No change was detected in either baseline
      spirometry or methacholine responsiveness. CONCLUSIONS: This suggests that if
      beta 2-agonists induce a rebound bronchial hyperreactivity, it is not the result
      of the production of tolerance or a direct effect on bronchial smooth muscle.

PMID- 8547731
TI  - Meta-analysis of parenteral clindamycin dosing regimens.
AB  - OBJECTIVE: We used meta-analysis to compare clinical cure and success rates for
      parenteral clindamycin 600 mg q8h or 900 mg q8h therapy to treat adult
      intraabdominal or female pelvic infections. DATA SOURCES: We located English
      language articles describing clindamycin use in humans using MEDLINE,
      International Pharmaceutical Abstracts, and Embase and from personal and drug
      information center files, plus all article references. STUDY SELECTION: Eligible
      studies used parenteral clindamycin 600 mg q8h or 900 mg q8h to treat
      intraabdominal or pelvic infection in at least 1 arm of a study and provided a
      definition of clinical outcome. Accepted were comparative trials in adults who
      were not critically ill or expected to die. DATA SYNTHESIS: The DerSimonian and
      Laird method was used to calculate weighted overall success rates for cure and
      success (cure plus improved) rates along with 95% confidence intervals for each
      dosage in intraabdominal and pelvic infections. Regimens were compared with
      respect to both cure and success rates using the Mann-Whitney U test. MAIN
      RESULTS: Twenty-three articles were eligible for inclusion. Abdominal cure rates
      were 75.6% and 90.5% for clindamycin 600 mg q8h and 900 mg q8h, respectively (p =
      0.03): success rates were 89.8% and 92.5%, respectively (p = 0.29). Pelvic cure
      rates were 82.8% and 89.4%, respectively (p = 0.51): success rates were 87.2% and
      89.9%, respectively (p = 0.51). CONCLUSIONS: In pelvic infections, a dosage of
      clindamycin 600 mg q8h appears to be clinically acceptable for all patients.
      Although clinical outcomes for intraabdominal infections are generally similar
      for both regimens, the significantly higher cure rate with a dosage of
      clindamycin 900 mg q8h suggests that dosage recommendations should be patient
      specific.

PMID- 8547732
TI  - In vitro stability of ranitidine hydrochloride in enteral nutrient formulas.
AB  - OBJECTIVE: To determine the chemical stability and physical compatibility of
      ranitidine in enteral nutrient formulas. MEASUREMENTS: A stability-indicating
      HPLC assay was used to measure the recovery of ranitidine from tablet (dissolved
      in water) or syrup after up to 24 hours of in vitro incubation in a variety of
      enteral nutrient formulas. Ranitidine binding to components of the formulas was
      measured after ultrafiltration. RESULTS: Eight enteral nutrient formulas were
      studied, and more than 90% of added ranitidine was recovered from each formula
      after 24 hours. The amount of ranitidine bound to components of the formulas
      varied between 8% and 29%. No gross physical incompatibilities were seen and the
      pH of each formula changed by less than 0.1 pH units over 24 hours. CONCLUSIONS:
      Ranitidine from either tablet or syrup was stable in the enteral nutrient
      formulas studied. Administration of ranitidine by admixture into these enteral
      formulas may be feasible.

PMID- 8547733
TI  - Lymphopenic effect of carbamazepine in a patient with chronic lymphocytic
      leukemia.
AB  - OBJECTIVE: To report a dramatic and reproducible suppressive effect of
      carbamazepine on circulating lymphocytes in an elderly woman with chronic
      lymphocytic leukemia. CASE SUMMARY: An elderly woman taking phenytoin for a
      stroke-associated seizure disorder had lymphocyte count of 28,800 x 10(6)
      cells/L. Speculating an unusual lymphadenopathic effect of the phenytoin therapy,
      carbamazepine therapy was substituted. After 15 weeks of carbamazepine treatment,
      the lymphocyte count declined to 3200 x 10(6) cells/L. Because of severe
      diarrhea, carbamazepine therapy was stopped and phenytoin therapy was
      reinstituted. At the end of 4 months of phenytoin treatment, the lymphocyte count
      had increased to 23,200 x 10(6) cells/L. Phenytoin therapy was discontinued and
      carbamazepine therapy was begun. The lymphocyte count decreased to 10,700 x 10(6)
      cells/L. Severe diarrhea recurred and phenytoin treatment was reinstituted. Over
      12 days the lymphocyte count increased to 28,900 x 10(6) cells/L. Phenytoin
      therapy was stopped and valproic acid therapy was started. The lymphocyte count
      continued to increase during valproic acid therapy, reaching a peak of 114,300 x
      10(6) cells/L. DISCUSSION: In this patient with chronic lymphocytic leukemia,
      carbamazepine therapy had a significant and reproducible lymphopenic effect that
      was readily reversible upon discontinuation of the drug. Unfortunately, this
      effect was associated with severe diarrhea, preventing further attempts at
      exploiting this potentially beneficial action. CONCLUSIONS: Carbamazepine had a
      reproducible suppressive effect on lymphocyte counts in an elderly patient with
      chronic lymphocytic leukemia. This unique observation raises the possibility that
      carbamazepine therapy may have a useful effect in patients with chronic
      lymphocytic leukemia.

PMID- 8547734
TI  - Eosinophilia associated with bupropion.
AB  - OBJECTIVE: To describe the first incidence of eosinophilia following
      administration of bupropion. CASE SUMMARY: The patient was a 72-year-old woman
      admitted for evaluation of chest pain. During hospitalization, the eosinophil
      count reached 0.60 fraction of 1.00, with absolute eosinophil count of 6693 x
      10(6)/L and a white blood cell count of 18.5 x 10(9)/L. She had been receiving
      bupropion therapy for 5 days prior to this admission. DISCUSSION: Potential
      causes of the eosinophilia, including disease states and medications, were
      reviewed comprehensively and ruled out. A review of the literature (MEDLINE 1966
      1994) did not identify previous cases of eosinophilia associated with bupropion
      therapy. Causes of eosinophilia include parasitic infections, allergic diseases,
      and medication use. A proposed mechanism for the occurrence of eosinophilia in
      this patient is unknown. CONCLUSIONS: Considering the temporal sequence of
      events, drugs administered prior to the development of eosinophilia, and the
      rapid decline of the eosinophil count following discontinuation of the
      medication, bupropion appears to be the precipitating agent.

PMID- 8547735
TI  - Shock, metabolic acidosis, and coma following ibuprofen overdose in a child.
AB  - OBJECTIVE: To report a child who developed shock, loss of consciousness, and
      metabolic acidosis following an ibuprofen overdose. CASE SUMMARY: A 6-year-old
      boy with no prior medical problems ingested approximately thirty 200-mg tablets
      of ibuprofen. The patient developed shock, coma, and metabolic acidosis. He was
      treated successfully with intubation and mechanical ventilation, fluid
      resuscitation, and decontamination with activated charcoal. The patient was
      discharged without any clinical sequelae. DISCUSSION: Serious adverse
      complications following ibuprofen overdose have been reported rarely in children.
      We reviewed literature pertaining to the etiology, pharmacology, pathophysiology,
      and management of complications following ibuprofen overdoses, as well as other
      case reports. CONCLUSIONS: Coma, metabolic acidosis, and shock were noted in a
      child who ingested a large quantity of ibuprofen. These complications have been
      described rarely in children. We attribute his favorable clinical outcome to
      early and aggressive intervention consisting of tracheal intubation, fluid
      resuscitation, and decontamination with activated charcoal. Although ibuprofen
      overdoses are usually benign, healthcare professionals should be aware of the
      various potentially serious complications that may occur.

PMID- 8547737
TI  - Application of International Consensus Meeting Criteria for classifying drug
      induced liver disorders.
AB  - OBJECTIVE: To report a patient with 2 consecutive reversible drug-induced liver
      disorders and the application of International Consensus Meeting Criteria for the
      screening and diagnosis of drug-induced liver disorders. CASE SUMMARY: An 88-year
      old man in a chronic care institution developed abdominal discomfort and jaundice
      after finishing a 10-day course of trimethoprim/sulfamethoxazole therapy for a
      urinary tract infection (UTI). The jaundice and the symptoms resolved
      spontaneously and the final diagnosis was symptomatic drug-induced liver injury,
      mixed type. After 1 month, the same patient received a course of cefadroxil
      therapy for another UTI. He developed an asymptomatic drug-induced liver injury,
      mixed type. Six months later, the patient received oral penicillin therapy and
      then ciprofloxacin, with no change in his liver function test results.
      DISCUSSION: To our knowledge, there are only a few other reports in the
      literature of a drug-induced liver injury with cefadroxil therapy; more cases are
      reported with trimethoprim/sulfamethoxazole than with cefadroxil. The criteria of
      an International Consensus Meeting were helpful to evaluate both incidences of
      liver injury in this patient with the aim of establishing the diagnosis and
      causality assessment. Additionally, the criteria were used to show that the
      patient had 2 separate liver injuries. CONCLUSIONS: Screening and diagnosis of
      drug-induced liver disorders depend on careful history taking and 5 specific
      biochemical liver tests. The evolution of the liver disorder induced by
      cefadroxil therapy probably was interrupted because of its early detection.
      Appropriate screening was done with the subsequent administration of new
      potentially hepatotoxic drugs.

PMID- 8547736
TI  - Topical fumagillin in the treatment of microsporidial keratoconjunctivitis in
      AIDS.
AB  - OBJECTIVE: To report microsporidial keratoconjunctivitis in a patient infected
      with HIV who was treated with topical fumagillin. CASE SUMMARY: A 37-year-old
      white man who was experiencing redness, pain, irritation, decreased vision, and a
      foreign body sensation occurring in both eyes was referred to the ophthalmology
      clinic. The patient had a medical history significant for AIDS, Pneumocystis
      carinii pneumonia, and Cytomegalovirus retinitis. Conjunctival smears were taken
      and stained positive for the presence of Microsporidia. The patient was diagnosed
      with bilateral microsporidial keratoconjunctivitis and fumagillin therapy was
      initiated. After 5 days of therapy, the patient reported significant improvements
      characterized by a decrease in blurred vision with only slight blurring in the
      left eye, decrease in headache, and decreased foreign body sensation. The patient
      continued topical fumagillin therapy for more than 14 months, with only slight
      blurring in the left eye and no apparent ocular toxicity as a result of
      fumagillin therapy. DISCUSSION: Although rare in occurrence, increasing numbers
      of documented microsporidial infections are being reported in the medical
      literature, particularly in individuals who are seropositive for HIV. Clinicians
      need to be cognizant of microsporidial keratoconjunctivitis as another
      opportunistic infection in this patient population. CONCLUSIONS: Although a
      curative agent has yet to be discovered, fumagillin represents a safe, effective,
      low-cost, topical agent for the treatment of microsporidial keratoconjunctivitis.

PMID- 8547738
TI  - Approaches to the treatment of hyperlipidemia in the solid organ transplant
      recipient.
AB  - OBJECTIVE: To review the literature investigating increased lipid concentrations
      in transplant recipients and the use of lipid-lowering agents in this population.
      DATA SOURCES: Relevant articles were identified from a MEDLINE search using the
      terms transplantation, hyperlipidemia, immunosuppression, and therapy including
      diet, gemfibrozil, bile acid sequestrants, nicotinic acid, probucol, and
      hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Selected
      literature, including controlled studies, was used in this review. STUDY
      SELECTION: Articles published since 1970 pertaining to hyperlipidemia in solid
      organ transplant recipients. Emphasis was placed on clinical trials that
      investigated approaches to the treatment of hyperlipidemia in transplant
      recipients. DATA EXTRACTION: Original articles and reviews were obtained to
      select material pertinent to the objectives. DATA SYNTHESIS: Descriptions of
      lipid concentrations in the transplant patient and treatment approaches used,
      including potential complications, were reviewed. CONCLUSIONS: Hyperlipidemia is
      an important risk factor for coronary heart disease in the solid organ transplant
      patient. Treatment alternatives include diet modification and, in most cases,
      pharmacologic intervention that should be based on the type of hyperlipidemia.
      The HMG-CoA reductase inhibitors are effective agents in the treatment of
      hyperlipidemia in the transplant recipient and generally are used as single
      therapy in low dosages to minimize the risk of myositis or rhabdomyolysis.

PMID- 8547739
TI  - Thrombosis and the pharmacology of antithrombotic agents.
AB  - OBJECTIVE: To provide an overview of the current state of knowledge regarding the
      physiology of hemostasis, the pathophysiology of thrombosis, and the pharmacology
      of antithrombotic agents. DATA SOURCES: A MEDLINE search was conducted to
      identify pertinent literature published since 1984. Recently published textbooks
      devoted to the subjects of hematology, hemostasis, and thrombosis also were
      reviewed, particularly their bibliographies. The bibliographies of selected
      review articles also were reviewed. STUDY SELECTION: As the amount of literature
      was vast, only the most significant and noteworthy published studies were
      reviewed. Review articles and book chapters authored by researchers of
      international reputation also were reviewed. DATA EXTRACTION: Identified studies
      from the primary literature and selected reviews were analyzed carefully.
      Information regarding hemostasis, thrombosis, and antithrombotic drugs was
      extracted. Particular attention was given to data regarding drugs currently
      available or soon to be available on the US market. DATA SYNTHESIS: Knowledge
      regarding the regulation of blood coagulation has expanded substantially in
      recent years. Hemostasis involves the dynamic interplay of numerous intravascular
      constituents, including the vessel wall, circulating procoagulants and
      anticoagulants, platelets, and fibrinolytic proteins. Thrombosis is the abnormal
      formation of a clot within the vascular system. When sufficiently large, thrombi
      can prevent the flow of blood and nutrients to vital tissues. Thrombosis is
      associated with many common diseases and is among the leading causes of death in
      developed countries. Many drugs are now available to prevent the formation and
      propagation of thrombi. These agents work by different pharmacologic mechanisms
      and are useful in different clinical situations. CONCLUSIONS: Thrombosis research
      has increased our understanding of the pharmacology of antithrombotic drugs and
      promoted the discovery of new agents targeted more specifically toward the
      critical steps in pathologic clot formation. New agents have the potential for
      greater efficacy and fewer adverse effects. An increased understanding of
      hemostasis, thrombosis, and the pharmacology of antithrombotic drugs should
      enable the clinician to use these agents appropriately.

PMID- 8547740
TI  - Macrolides versus azalides: a drug interaction update.
AB  - OBJECTIVE: To describe the current drug interaction profiles for all approved and
      investigational macrolide and azalide antimicrobials, and to comment on the
      clinical impact of these interactions when appropriate. DATA SOURCES: MEDLINE was
      searched to identify all pertinent studies, review articles, and case reports
      from 1975 to 1995. When appropriate information was not available in the
      literature, data were obtained from the product manufacturers. STUDY SELECTION:
      All available data were reviewed to give an unbiased account of possible drug
      interactions. DATA EXTRACTION: Data for some of the interactions were not
      available from the literature, but were available from abstracts or from company
      supplied materials. Although the data were not always entirely explicative, the
      best attempt was made to deliver the pertinent information that clinical
      practitioners would need to formulate practice opinions. When more in-depth
      information was supplied in the form of a review or study report, a thorough
      explanation of pertinent methodology was supplied. DATA SYNTHESIS: Since the
      introduction of erythromycin into clinical practice, there have been several
      clinically significant drug interactions identified throughout the literature
      associated with this drug. These interactions have been caused mostly by
      inhibition of the CYP3A subclass of hepatic enzymes, thereby decreasing the
      metabolism of any other agent given concurrently that is also cleared through
      this mechanism. With the development and marketing of several new macrolides, it
      was hoped that the drug interaction profile associated with this class would
      improve. This has been met with variable success. Although some of the extensions
      of the 14-membered ring macrolides have shown an incidence of interactions equal
      to that of erythromycin, others have shown improved profiles. In contrast, the 16
      membered ring macrolides have demonstrated a much improved, though not absent,
      interaction profile. The most success in avoiding drug interactions through
      structure modification has been accomplished with the development of the azalide
      class, of which azithromycin is the first to be approved for marketing. This
      agent has to date produced none of the classic drug interactions that most
      macrolides have demonstrated in patient care. CONCLUSIONS: The introduction of
      new 14- and 16-membered ring macrolides appears to have had a variable effect in
      modifying the incidence of drug interactions associated with this class.
      Azithromycin, a member of the new azalide class, has to date produced fewer
      clinically significant interactions than other azalides with any agent that is
      cleared through the CYP3A system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547741
TI  - Efficacy of mesna for prevention of hemorrhagic cystitis after high-dose
      cyclophosphamide therapy.
AB  - For these reasons, a definitive statement about the relative efficacy of mesna
      for prophylaxis of cyclophosphamide-associated HC in BMT patients cannot be made.
      Because HC is a frequent and potentially serious complication of high-dose
      cyclophosphamide therapy, the implementation of some preventive measure is
      mandatory in all patients. Unless medically contraindicated, provision of
      sufficient hydration and diuresis to maintain adequate high urine flow should be
      a component of all prophylactic regimens. It is unclear whether the addition of
      mesna therapy or bladder irrigation to intravenous hydration provides greater
      protection. Studies indicate that mesna probably has no adverse effect on
      engraftment. This is consistent with its chemistry and pharmacology, as the drug
      is hydrophilic and activated only in the kidneys. Thus, it is inactive in the
      bloodstream and unable to penetrate cell membranes and interfere with the action
      of cyclophosphamide. Although safety issues surrounding the use of mesna for
      prevention of cyclophosphamide-associated HC appear to have been resolved,
      efficacy issues must await the completion of further well-controlled comparative
      trials.

PMID- 8547742
TI  - Antifungal prophylaxis in bone marrow transplant.
AB  - The benefits of fungal prophylaxis with fluconazole in BMT patients appear to
      outweigh the risks of a possible increase in colonization and infection by C.
      krusei or T. glabrata. Disseminated fungal infections caused by C. tropicalis and
      C. albicans have a 38.8% mortality rate, and these infections may be prevented by
      the prophylactic use of fluconazole. C. krusei and T. glabrata infections
      generally do not contribute to increased mortality, and most patients infected by
      these organisms recover after appropriate antifungal therapy. The use of
      amphotericin B as prophylaxis may have some efficacy. One retrospective study
      found low-dose amphotericin B therapy to be effective in preventing Candida
      infections, but results from a placebo-controlled, randomized prospective trial
      with 0.1 mg/kg/d failed to support this claim. Low-dose amphotericin B
      prophylaxis (0.1-0.25 mg/kg/d) shows promise against aspergillosis, an
      opportunistic infection associated with high morbidity and mortality. The
      literature suggests the possible value of using oral or intravenous fluconazole
      200-400 mg/d or intravenous amphotericin B 0.1-0.25 mg/kg/d as antifungal
      prophylaxis in patients after autologous or allogeneic BMT. Many questions remain
      unanswered, however. These studies described the potential decrease in morbidity
      and mortality of BMT patients with the use of either fluconazole or amphotericin
      B, but it is not known whether all patients after BMT or only those at high risk
      of fungal infection may benefit from prophylaxis. Optimal dosing of either
      antifungal agent has not been defined in the studies. Clinicians should be aware
      of the possible increase in colonization by less pathogenic fungal species, such
      as C. krusel and T. glabrata, when prescribing fluconazole prophylaxis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8547743
TI  - Medicine, pharmacy, and industry--a fly's eye view of health care.

PMID- 8547744
TI  - Erythromycin-induced hypotension.

PMID- 8547745
TI  - Effect of dexamethasone on the decrease of serum phenytoin concentrations.

PMID- 8547746
TI  - Cefazolin use in clinically severe obese patients undergoing gastric restrictive
      surgery.

PMID- 8547747
TI  - Hypersensitivity reaction during prolonged use of piperacillin/tazobactam in
      treatment of osteomyelitis.

PMID- 8547748
TI  - Polyarthralgia associated with prazosin use.

PMID- 8547749
TI  - Probable terfenadine-fluoxetine-associated cardiac toxicity.

PMID- 8547750
TI  - Adenosine use in a pregnant patient with supraventricular tachycardia.

PMID- 8547751
TI  - Itraconazole does not interfere with fluorescence polarization immunoassay of
      serum digoxin.

PMID- 8547752
TI  - Comment: pharmacokinetic variability of aminoglycosides.

PMID- 8547753
TI  - Comment: adjuvant therapy decisions in node-negative breast cancer.

PMID- 8547755
TI  - Comment: selected topics in drug information access and practice: an update.

PMID- 8547754
TI  - Comment: cyclosporine and vancomycin disposition during continuous venovenous
      hemodiafiltration.

PMID- 8547756
TI  - Comment: substantiation in pharmacoeconomic evaluations.

PMID- 8547757
TI  - Looking with one's mind's eye.
AB  - On the basis of clinical cases reported in the literature, an attempt is made to
      show that conscious mental representations of written words have a left-right
      dimension similar to their counterparts in the physical world. They may,
      therefore, be affected by unilateral neglect in much the same way as words on a
      written or printed page. Usually, real words and their representations run in the
      same direction. However, in some cases, they appear to run in opposite directions
      and this may result in the production of mirror writing.

PMID- 8547758
TI  - What makes a therapy? Some parameters of therapeutic intervention in aphasia.
AB  - It has often been assumed that detailed analyses of aphasic impairments would be
      both necessary and sufficient for the development of remediation programmes. In
      this paper, we argue that the analysis of the impairment is a necessary but not
      sufficient precondition for therapy. Adequate remediation programmes require the
      development of an independent theory of therapy that provides a detailed
      specification of the different components of the therapeutic process. Therapy can
      be shown to have as many interacting components as the impairment itself. In this
      paper, we try to identify some of the components of the therapy process by
      comparing different therapy programmes that have been employed in the remediation
      of 'mapping deficits' in agrammatism.

PMID- 8547759
TI  - Profiling agrammatic spoken language: towards a government and binding framework.
AB  - An analytical procedure for describing agrammatic spoken language based on
      government and binding theory is used to characterise the spoken grammar of an
      aphasic adult (JR) with severe agrammatism. Analysis of JR's spoken language
      revealed that he produced a greater number of single-word utterances (single
      lexical items) in comparison with lexical and/or functional projections. both
      morphological and syntactic evidence suggested that JR retained a differentiated
      set of lexical categories. No violations of word order were found. Target
      determiners and target inflection phrases were not always correctly realised. No
      'complementiser' phrases or complex sentences were produced by JR. Analysis of
      the data collected suggests that JR's morphosyntactic abilities were not 'lost',
      but rather specific morphosyntactic representations were inaccessible. We
      hypothesise that his deficit is best characterised (rather loosely, in the
      absence of a clear and full account of language-processing impairments, and other
      theoretical evidence) as a deficit in performance rather than in competence.
      Implications of the results of the analysis for intervention are discussed as are
      future plans for adaptation of the profile into a clinically useful procedure.

PMID- 8547760
TI  - Profiling fluent aphasic spontaneous speech: a comparison of two methodologies.
AB  - Grammatical features of fluent aphasic speakers have not received as much
      attention as those exhibited by non-fluent aphasic speakers. In part, this
      neglect reflects the difficulty of applying consistent analytical procedures to
      fluent aphasic speech. For the analytical process to be meaningful, the
      methodology must be robust, replicable and capable of dealing with the voluble
      and non-specific output which is often typical of these speakers, and yet be
      sensitive enough to reveal subtle grammatical differences between aphasic and
      normal speech. In this paper the methodological problems encountered in applying
      analytical procedures to spontaneous speech data are discussed. Two different
      procedures for analysing speech data are compared and applied to samples of
      fluent aphasic and normal speech. Both procedures reveal that (compared with
      normal speakers), although these aphasic speakers are capable of producing some
      well-constructed grammatical structures, the distribution of these structures may
      differ compared with the distribution exhibited by normal speakers. These results
      suggest that complex aspects of grammatical organisation may be compromised in
      some fluent aphasic speakers.

PMID- 8547761
TI  - Pronunciation errors in acquired speech disorders: the errors of our ways.
AB  - There are conflicting arguments over whether perceptual analysis of speech errors
      can be used for a differential diagnosis of acquired motor speech disorders. This
      study addressed the issue using a narrow phonetic transcription of single-word
      naming and repetition responses, and a comprehensive taxonomy of error types.
      Speaker groups were selected according to criteria which were not variables to be
      investigated later. The listener-perceived segmental errors of 30 post-stroke
      speech-impaired speakers (six spastic dysarthric; 12 speech dyspraxic and
      phonemic paraphasic without dysphasia; 12 speech dyspraxic and phonemic
      paraphasic with dysphasia) were analysed and subjected to statistical analysis. A
      variety of analyses failed to establish any consistently reliable differential
      diagnostic pointers. It is concluded that reasons for the inconclusiveness of
      perceptual assessment go beyond investigatory methodological problems and embrace
      issues of underlying theory as well.

PMID- 8547762
TI  - Lexical-semantic deficits following right hemisphere damage: evidence from verbal
      fluency tasks.
AB  - The evidence of lexical-semantic deficits following right, non-language-dominant
      hemisphere injury was assessed using word (or verbal) fluency tests. Two groups
      of subjects (non-brain-damaged controls and right hemisphere-damaged patients)
      were indistinguishable in their performances on convergent lexical tasks.
      Subjects completed verbal fluency tasks by five semantic criteria. The brain
      damaged subjects produced significantly fewer responses on two of the categories
      and demonstrated fewer lexical retrieval strategies. The results were interpreted
      as evidence that lexical-semantic knowledge is largely intact following right
      hemisphere damage, and that apparent lexical deficits result from failure to use
      lexical knowledge flexibility, suggesting that right-hemisphere language
      disorders may stem from broader cognitive failures.

PMID- 8547763
TI  - Applying conversation analysis to aphasia: clinical implications and analytic
      issues.
AB  - This paper explores the impact of linguistic impairments on conversational
      ability in aphasia using conversation analysis (CA). Using a combination of
      quantitative and qualitative techniques, an analysis of the distribution of turns
      at talk in three aphasic participants' conversations with a relative and with the
      researcher is described. Using extracts from the conversations for illustration,
      three major factors are proposed which influence the sharing of conversational
      turns: (1) shared knowledge of interlocutors, (2) the manifestations of
      linguistic impairments in conversation, and (3) individual discourse styles.
      Finally, the implications of the findings for remediation are considered.

PMID- 8547764
TI  - Characterising thematic role assignment in aphasic sentence production:
      procedures for elicited and spontaneous output.
AB  - This paper describes two assessment tools developed to assist in characterising
      certain anomias that may be best understood within a sentence-processing
      paradigm. Although sentence-processing models promise to contribute much to our
      understanding of a range of aphasic deficits, the lack of available tools to
      measure and monitor sentence behaviour has been a limiting factor both
      theoretically and clinically. Based on proposals that the process of thematic
      role assignment may be influential in some anomias, two tools were developed to
      profile thematic role realisation across elicited and spontaneous speech
      conditions. The first measure provides an opportunity to contrast word retrieval
      across elicited single-word and sentence contexts, whereas the second measure
      permits an examination of thematic role realisation in spontaneous output. The
      data from two case studies are presented to demonstrate application of the tools.

PMID- 8547765
TI  - In vivo axial rotations and neutral zones of the thoracolumbar spine.
AB  - Fourteen normal male subjects with mean age 23 (range 20-32) years and mean body
      weight of 69.6 kg underwent right and left axial rotation in a special machine-
      axial rotation tester (AROT). The AROT was designed and fabricated such as to
      allow uninhibited coupled axial rotation and lateral flexion while preventing
      flexion and extension. The range of rotation (ROR) and neutral zone (NZ) were
      recorded during active rotation (.A), active rotation with blindfold (.B), and
      passive rotation with blindfold (.P). Finally, bilateral axial rotation was
      tested with 6, 12, 18, 24, 30, and 36 Nm rotary torque (.T). There was no
      significant difference between ROR.A and ROR.B, both being approximately 140
      degrees. However, there was a significant difference between NZ.A and NZ.B (p <
      0.01). ROR.P was approximately 30 degrees greater than ROR.A. The trunk
      structures showed a nonlinear viscoelastic behavior with progressive rotary
      torque application. The neutral zone in axial rotation did not show significant
      difference between different loads. It is reported that the rotary neutral zone
      varies between subjects, and it is suggested to be contributory to spinal laxity.

PMID- 8547766
TI  - A mathematical lifting model of the lumbar spine.
AB  - The objective of this study was to develop a comprehensive mathematical lifting
      model which takes into account both task and personal factors. The outcome
      measure of this model was compared to that of the 1981 and 1991 NIOSH lifting
      equations as well as the model reported by Drury and Pfeil (Int J Prod Res
      13:137, 1975). The model was developed in two stages. In the first stage, the
      complete model was derived from the psychophysical data. In the second stage, the
      discounting factors of the various parameters included in the model were tested
      and adjusted using the physiological and biomechanical data. The rationale for
      building the model in two stages was based upon the hypothesis proposed and
      tested by Karwowski (Proc Ergon Soc Conf 95, 1983), which, combining the
      acceptability of physiological and biomechanical stresses, should lead to an
      overall measure of lifting task acceptability--namely, the acceptability of
      psychophysical stress. The following input parameters were incorporated into the
      model: (a) horizontal distance in the sagittal plane, (b) vertical distance
      between the origin of lift and the floor, (c) vertical travel distance, (d)
      lifting frequency, (e) task duration, (f) twisting angle, (g) coupling, (h) heat
      stress, (i) gender, (j) age, (k) body weight, and (l) percentage of worker
      population. The lifting capacity values predicted from the present study are
      consistently lower than the values generated from prior research. This can
      largely be explained by the incorporation of new biomechanical and physiological
      guidelines for lifting tasks.

PMID- 8547767
TI  - Treatment of postoperative wound infections following spinal fusion with
      instrumentation.
AB  - Postoperative wound infections following spinal fusion with instrumentation often
      present diagnostic and therapeutic difficulties. This article reviews 34 such
      infections. An infection rate of 3.7% was noted. Depending on various clinical
      indicators, treatment strategies included short-course antibiotics, prolonged
      intravenous antibiotics, or intravenous antibiotics followed by suppressive
      antibiotics and eventual hardware removal. To eradicate these infections, removal
      of instrumentation is often required; this option, however, may result in an
      unstable spine. Treatment algorithms were developed for treatment of
      postoperative spinal surgical site infections and to minimize the possibility of
      spine instability. All patients were cured of their infections.

PMID- 8547768
TI  - Orthosis as prognostic instrument in lumbar fusion: no predictive value in 50
      cases followed prospectively.
AB  - To evaluate pain relief in a lumbar orthosis as a predictor for good clinical
      results after solid fusion, all patients scheduled for such a surgical procedure
      were preoperatively encouraged to use an orthosis, soft or rigid, for 3 weeks.
      Grade of back pain relief as a percent using the orthosis was assessed by the
      patients and was registered before surgery. After surgery, at 1-year follow-up,
      patients with nonunion demonstrated radiographically were excluded from the
      series. Thus, 50 patients with solid fusion could be identified and followed for
      at least 2 years prospectively. At follow-up these 50 patients graded the pain
      relief induced by the fusion. In the preoperative corset test, 31 patients
      experienced significant back pain relief, meaning a reduction of at least 50%. No
      applicable correlation was found, however, between outcome in this corset test
      and the eventual clinical result expressed as improvement/no improvement after
      solid fusion. The two types of orthoses did not differ in this aspect. We
      conclude that the orthosis, rigid or soft, is not a useful instrument when
      selecting patients for lumbar fusion.

PMID- 8547770
TI  - The diagnostic utility of dermatomal evoked potentials.
AB  - A study was completed to evaluate the diagnostic utility of dermatomal evoked
      potentials (EPs) for identifying single and multiple sensory nerve root
      compromise. We examined the clinical records of 37 patients referred for neck and
      lower back pain with particular attention paid to presenting clinical symptoms,
      magnetic resonance (MR) imaging results, and cervical and/or lumbar dermatomal EP
      results. The primary object of this study was to determine whether or not
      dermatomal EPs provided useful diagnostic information about nerve root function
      that would supplement the structural information provided by the MR imaging. We
      evaluated an outpatient population presenting with neck and lower back pain.
      These patients had detailed clinical evaluations, MR images, and EP evaluations,
      each done by independent sources. EP studies included mixed nerve EPs (ulnar and
      median or tibial nerve), and either C6 and C8 or L4, L5, and S1 dermatomal EPs
      for cervical and lumbar disorders, respectively. Mixed nerve and dermatomal EPs
      provided reliable information about nerve root function that corresponded to
      clinical symptoms more closely than did the MR findings. Specifically, these EPs
      often provided additional information about lateralized nerve root dysfunction
      beyond that given by the MR imaging. In some cases, EPs identified disturbances
      in nerve root function in the absence of MR-imaging-identified structural
      abnormality.

PMID- 8547769
TI  - The significance of dorsal migration of the cord after extensive cervical
      laminectomy for patients with traumatic central cord syndrome.
AB  - Central cord syndrome (CCS) resulting from traumatic cervical injury is often
      associated with cervical stenosis and/or spondylosis. The efficacy of multilevel
      laminectomy in the treatment of this condition has been controversial. The
      objective of this study was to validate by magnetic resonance (MR) imaging the
      occurrence of dorsal cord migration after extensive laminectomy for patients with
      the clinical syndrome of central cord damage and its relationship to the short
      term outcome. During a 28-month period, the authors evaluated 20 patients (mean
      age 54 years) who sustained CCS after cervical spine trauma. Pre- and
      postoperative MR imaging assessed the adequacy of cervical cord decompression by
      multilevel laminectomy. All patients had cervical canal stenosis with complete
      obliteration of the anterior subarachnoid space over multiple levels. Seventeen
      patients initially had CCS of different degrees of severity. One had no motor
      deficit and two had motor complete with sensory deficits greater in their arms.
      Laminectomy, generally from C2 to C7 without facetectomy, was performed after
      plateau of neurological recovery (mean 17 days postinjury). Neurological
      assessment 3 months after operation revealed improvement in 12, stable function
      in 7, and progression of deficit in one with no mortality. The postoperative
      midsagittal MR images demonstrated adequate decompression with restoration of
      anterior cerebrospinal fluid space and posterior cord migration in 12 patients
      (60% of the 20), but only 8 of them also had improved function. MR imaging
      demonstrated that, in the presence of multilevel spondylosis/stenosis,
      laminectomy may provide adequate spinal cord decompression in patients with
      traumatic CCS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547771
TI  - Magnetic stimulation as a diagnostic tool in cervical nerve root compression and
      compression-induced neuropathy.
AB  - Magnetic stimulation of motor cortex and cervical spinal cord was used to assess
      motor impairment in patients with either cervical nerve root compression or
      myelopathy. Evoked potentials were recorded from biceps brachii and abductor
      pollicis brevis. Our interest centered on whether the paresis resulting from root
      compression is accompanied by an increased latency of magnetically evoked muscle
      potentials and whether latency is increased in cases of cervical root compression
      or myelopathy in which no paresis occurs. Latency increase does appear to be a
      moderately good indicator of disturbed nerve conduction. In particular, prolonged
      latencies in cases of "subclinical" paresis could be used as an important
      diagnostic tool for the early detection of motor deficits in cervical compression
      radiculopathy and myelopathy.

PMID- 8547772
TI  - Magnetic resonance angiographic diagnosis of ectatic vertebral artery.
AB  - In the cervical spine, routine and contrast magnetic resonance (MR)- and computed
      tomography (CT)-based studies may fail to differentiate between an ectatic
      vertebral artery and a solid foraminal mass. A complete cervical and lumbar Myelo
      CT scan in a 67-year-old female with lumbar stenosis revealed an incidental, left
      sided C3-C4 foraminal mass. A vascular lesion was suspected when the MR study
      revealed the lesion to be a signal void. MR angiography confirmed an ectatic C3
      C4 vertebral artery loop. The possibility of a vertebral artery anomaly should be
      considered in patients with asymptomatic lateral and foraminal cervical lesions
      on CT studies. In these patients, routine MR and MR angiography are necessary to
      demonstrate the status of the vertebral artery in the foramen.

PMID- 8547773
TI  - Isolated muscle atrophy of the distal upper extremity in cervical spinal cord
      compressive disorders.
AB  - The purpose of this article is to clarify one mechanism of muscular atrophy of
      the distal upper extremity that we attribute to cervical compression (Hirayama
      type amyotrophy) by medical imaging and anatomical studies of the cervical spine.
      Five young male patients (mean age: 22.6 years) with this disorder showed
      characteristic findings to include an abnormal anterior displacement of the
      posterior dura wall in flexion that resulted in an anteroposterior compression of
      the spinal cord segment from C7 to C8. To identify an anatomical relationship to
      this disorder, the lower cervical spine was studied using 11 embalmed adult human
      cadavers. Abundant posterior epidural ligaments were observed between the
      posterior dura mater and the ligamentum flavum. Posterior epidural ligaments in
      the cervical spine have not been reported previously. The anterior displacement
      of the dura mater may be attributed to a lack of and/or insufficiency of the
      posterior epidural ligaments.

PMID- 8547774
TI  - Anterior decompression and fusion for ossification of posterior longitudinal
      ligament in the thoracic spine.
AB  - Twelve cases are reviewed of ossification of posterior longitudinal ligament
      (OPLL) in the thoracic spine for which anterior decompression and fusion were
      performed. A transthoracic approach was used in 10 patients, and median
      sternotomy and a transsternal approach were used in one each. The clinical
      symptoms and the Japanese Orthopaedic Association (JOA) score improved in 10
      patients, whereas they were unchanged in two patients who underwent a revision
      operation for a previous laminectomy. An anterior procedure that results in
      adequate decompression of the spinal cord and good spinal stability is
      recommended for anterior lesions, such as OPLL, which compress the anterior
      spinal cord at each level of the thoracic spine.

PMID- 8547775
TI  - Spinal extradural angiolipoma.
AB  - We present a case of an extradural thoracic spinal angiolipoma in a 27-year-old
      woman. The epidural tumor was evaluated with computerized tomographic scans and
      magnetic resonance imaging scans. The tumor was removed, and the clinical
      symptoms improved remarkably.

PMID- 8547776
TI  - Total coccygectomy for the relief of coccygodynia: a retrospective review.
AB  - Nine of 10 patients operated on by a single surgeon were studied. Hospital
      records, radiographs, and a postal survey were used. Follow-up averaged 56
      months. Age at operation averaged 32.5 years. There were six males and three
      females. Symptoms had been present for 7 months to 14 years and all patients
      failed a course of non-operative therapy. All patients underwent a total
      coccygectomy by subperiosteal dissection through a longitudinal midline incision.
      There was one postoperative wound infection. All patients were satisfied with the
      surgical scars. Three patients reported "complete" pain relief, five reported
      "marked improvement," and one was "slightly improved." All nine patients were
      satisfied with the operation and would choose to have the surgery again.

PMID- 8547777
TI  - Thoracic disc herniation at T7-T8.

PMID- 8547778
TI  - Advances in Ultrafast Computed Tomography: 1995. An International Symposium on
      Electron Beam Tomography. Scottsdale, Arizona, October 6-8, 1995. Abstracts.

PMID- 8547779
TI  - Children's dental development--1: Birth to six years old.

PMID- 8547780
TI  - School nursing. A day out for children with special needs.

PMID- 8547781
TI  - Services for children with HIV/AIDS: the views of parents.
AB  - In this qualitative study, the parents of ten children who attended an inner
      London teaching hospital for HIV/AIDS were interviewed to find out their views on
      the services. Speaking from their own experiences, parents expressed a high level
      of satisfaction with the specialist paediatric care at the teaching hospital but
      had little confidence in the expertise of other hospitals or of GPs and health
      visitors. Few cases had been identified antenatally; the diagnosis of HIV/AIDS
      was often made only after the child had become ill and been investigated for a
      variety of diseases before being tested for HIV. The families felt considerable
      anxiety about the future, especially about what would happen if both child and
      parent were to become ill at the same time. The increasing number of HIV-infected
      mothers and children means that in future the caseload and expertise of the
      specialist centres will need to be shared with the primary health care team.

PMID- 8547782
TI  - Midwives: listen to your patients, believe their pain.

PMID- 8547783
TI  - Update on contraception 1: The pill and other hormonal methods.

PMID- 8547784
TI  - Bullying: its roots in pre-school aggression.

PMID- 8547785
TI  - Modern fetal heart monitoring at home and in hospital.

PMID- 8547786
TI  - The parietal system and some higher brain functions.

PMID- 8547787
TI  - Representing spatial information for limb movement: role of area 5 in the monkey.
AB  - How is spatial information for limb movement encoded in the brain? Computational
      and psychophysical studies suggest that beginning hand position, via-points, and
      target are specified relative to the body to afford a comparison between the
      sensory (e.g., kinesthetic) reafferences and the commands that generate limb
      movement. Here we propose that the superior parietal lobule (Brodmann area 5)
      might represent a substrate for a body-centered positional code. Monkeys made arm
      movements in different parts of 3D space in a reaction-time task. We found that
      the activity of area 5 neurons can be related to either the starting point, or
      the final point, or combinations of the two. Neural activity is monotonically
      tuned in a body-centered frame of reference, whose coordinates define the
      azimuth, elevation, and distance of the hand. Each spatial coordinate tends to be
      encoded in a different subpopulation of neurons. This parcellation could be a
      neural correlate of the psychophysical observation that these spatial parameters
      are processed in parallel and largely independent of each other in man.

PMID- 8547788
TI  - Deciding not to GO: neuronal correlates of response selection in a GO/NOGO task
      in primate premotor and parietal cortex.
AB  - Monkeys performed reaching movements in two opposite directions in a
      symmetrically rewarded GO/NOGO task with an instructed-delay period.
      Instructional cues were presented at the target locations. The decision not to
      move was clearly reflected in cell activity in dorsal premotor cortex, but not in
      parietal cortex area 5. In premotor cortex, the initial response (< 250 msec) of
      most cells to the appearance of the instructional cues in GO and NOGO trials was
      similar. However, by the end of the delay period, the responses of most cells
      were statistically different between the two trial types, and the population
      signals were much less directional in the NOGO trials than in the GO trials. In
      area 5, in contrast, single-cell and population signals were generally similar
      and strongly directional in both GO and NOGO trials. This result suggests a role
      for area 5 in visuomotor analysis for the guidance of limb movements. It further
      suggests that separate representations of potential motor responses to external
      inputs and of the intended response to that input can coexist in parietal and
      premotor cortex, respectively.

PMID- 8547789
TI  - Neural mechanisms of visual guidance of hand action in the parietal cortex of the
      monkey.
AB  - We studied the functional properties of the hand manipulation task-related
      neurons (N = 136) in the posterior bank of the intraparietal sulcus (IPS) using
      four kinds of objects for manipulation. We performed cluster analysis by
      comparing the profiles of activity of these neurons across objects during
      manipulation in the light, and classified them into nine groups, four highly
      selective, four moderately selective, and one nonselective group. Activity
      profiles of these neurons across objects were analyzed in four task conditions:
      object manipulation and object fixation both in the light and in the dark. Cells
      were classified as "motor-dominant," "visual-dominant," and "visual and motor"
      neurons, and the latter two were further subdivided into object type and non
      object type. Most of the highly selective neurons (35 of 136) preferred the same
      object for manipulation in the dark as in the light. The object type "visual and
      motor" neurons preferred the same object for manipulation and fixation,
      suggesting that these neurons play an important role in matching the pattern of
      hand movement to the visuo-spatial characteristics of the object to be
      manipulated. A large majority of highly selective hand manipulation neurons were
      localized in the rostral part of the posterior bank of IPS, which we designated
      as the anterior intraparietal (AIP) area. We propose a conceptual model of the
      system for visual guidance of hand action including parietal hand manipulation
      neurons.

PMID- 8547790
TI  - Dissociation of ophthalmokinetic and melokinetic attention in unilateral neglect.
AB  - A line cancellation task was performed by 36 right brain-damaged patients with
      unilateral neglect under four different conditions: normal and mirror-reversed
      view, with and without cueing. Two types of unilateral neglect were distinguished
      by directing ophthalmo- and melokinetic components of visuomanual scanning to
      opposite sides of the stimulus array. In ophthalmokinetic neglect, contralesional
      visual scanning of the stimulus array was defective, while manual scanning was
      unimpaired. The converse was true of melokinetic neglect. Ophthalmokinetic
      neglect was predominantly associated with posterior brain damage, while
      melokinetic neglect was predominantly associated with frontal or subcortical
      brain damage. In a few instances, cueing visuomanual scanning toward the
      neglected side of the stimulus array converted ophthalmokinetic into melokinetic
      neglect, and vice versa. The results are held to be indicative of two components
      of space representation and to provide further evidence of response-driven
      modulation of perceptual awareness.

PMID- 8547791
TI  - Neurophysiological evidence for a role of posterior parietal cortex in
      redirecting visual attention.
AB  - Lesions of the posterior parietal cortex in humans and monkeys result in a
      spatial neglect syndrome characterized by defects in visual-spatial perception,
      oculomotor function, and directing visual attention. Although symptoms of spatial
      neglect can result from lesions to other cortical and subcortical areas, patients
      with posterior parietal lesions are particularly impaired in their ability to
      disengage and reorient visual attention. Neurophysiological experiments in area
      7a of behaving monkeys reveal a large class of neurons that respond to visual
      stimuli and are powerfully modulated by states of attention. These cells respond
      better to passive visual stimuli presented during states of attentive fixation
      than to identical stimuli presented in nonattentive states. The responses of the
      majority of these cells are also influenced by covert shifts of attention away
      from the point of fixation; they respond to stimuli presented anywhere within
      their receptive fields except the covertly attended location. The combined effect
      of facilitation during attentive fixation and lack of response at the attended
      location results in a sensitivity for visual stimuli that appear at one location
      while attention is directed to another. The special sensitivity for unattended
      stimuli in this group of neurons in area 7a suggests that they may play a role in
      reorienting attention, possibly by providing signals of the spatial locations of
      novel stimuli.

PMID- 8547792
TI  - Encoding of intention and spatial location in the posterior parietal cortex.
AB  - The posterior parietal cortex is functionally situated between sensory cortex and
      motor cortex. The responses of cells in this area are difficult to classify as
      strictly sensory or motor, since many have both sensory- and movement-related
      activities, as well as activities related to higher cognitive functions such as
      attention and intention. In this review we will provide evidence that the
      posterior parietal cortex is an interface between sensory and motor structures
      and performs various functions important for sensory-motor integration. The
      review will focus on two specific sensory-motor tasks--the formation of motor
      plans and the abstract representation of space. Cells in the lateral
      intraparietal area, a subdivision of the parietal cortex, have activity related
      to eye movements the animal intends to make. This finding represents the lowest
      stage in the sensory-motor cortical pathway in which activity related to
      intention has been found and may represent the cortical stage in which sensory
      signals go "over the hump" to become intentions and plans to make movements. The
      second part of the review will discuss the representation of space in the
      posterior parietal cortex. Encoding spatial locations is an essential step in
      sensory-motor transformations. Since movements are made to locations in space,
      these locations should be coded invariant of eye and head position or the sensory
      modality signaling the target for a movement. Data will be reviewed demonstrating
      that there exists in the posterior parietal cortex an abstract representation of
      space that is constructed from the integration of visual, auditory, vestibular,
      eye position, and proprioceptive head position signals. This representation is in
      the form of a population code and the above signals are not combined in a
      haphazard fashion. Rather, they are brought together using a specific operation
      to form "planar gain fields" that are the common foundation of the population
      code for the neural construct of space.

PMID- 8547793
TI  - Oculocentric spatial representation in parietal cortex.
AB  - Parietal cortex comprises several distinct areas. Neurons in each area are
      selective for particular stimulus dimensions and particular regions of space. The
      representation of space in a given area reflects a particular motor output by
      which a stimulus can be acquired. Neurons in the lateral intraparietal area (LIP)
      are active in relation to both visual and motor events. LIP neurons do not
      transmit an unambiguous saccadic command. Rather, they signal the location at
      which an event has occurred. These spatial locations are encoded in oculocentric
      coordinates, that is, with respect to the current or anticipated position of the
      center of gaze. When an eye movement brings the spatial location of a recently
      flashed stimulus into the receptive field of an LIP neuron, the neuron responds
      to the memory trace of that stimulus. This result indicates that, for nearly all
      LIP neurons, stored visual information is remapped in conjunction with saccades.
      Remapping of the memory trace maintains the alignment between the current image
      on the retina and the stored representation in cortex. Further, when an eye
      movement is about to occur, more than a third of LIP neurons transiently shift
      the location of their receptive fields. This anticipatory remapping allows the
      neuron to begin to respond to a visual stimulus even before the saccade is
      initiated that will bring the stimulus into the fixation-defined receptive field.
      Both kinds of remapping serve to create a constantly updated representation of
      stimulus location that is always in terms of distance and direction from the
      fovea. This oculocentric representation has the advantage that it already matches
      that known to exist in the frontal eye fields and the superior colliculus, the
      output targets of LIP, and it does not require further coordinate transformation
      in order to contribute to spatially accurate behavior. These results indicate
      that LIP can analyze visual space without ever forming a representation of
      absolute target position.

PMID- 8547794
TI  - The case of the unknown managed care quality system.

PMID- 8547795
TI  - Developing a quality improvement database using health insurance data: a guided
      tour with application to Medicare's National Claims History file.
AB  - Health policy researchers are increasingly turning to insurance claims to provide
      timely information on cost, utilization, and quality trends in health care
      markets. This research offers an in-depth description of how to systematically
      transform raw inpatient and ambulatory claims data into useful information for
      health care management and research using the Health Care Financing
      Administration's National Claims History file as an example. The topics covered
      include: (a) understanding the contents and architecture of claims data, (b)
      creating analytic files from raw claims, (c) technical innovations for health
      policy studies, (d) assessing data accuracy, (d) the costs of using claims data,
      and (e) ensuring confidentiality. In summary, claims data are found to have great
      potential for quality of care analysis. As in any analysis, careful development
      of a database is required for scientific research. The methods outlined in this
      study offer health data novices as well as experienced analysts a series of
      strategies to maximize the value of claims data for health policy analysis.

PMID- 8547796
TI  - Primary care as form or content?
AB  - This article advocates revisiting the notion of primary care to include these
      dimensions: the physician-patient relationship, the notion of principal care, and
      the patient as validating the primary care relationship. The quality of primary
      care rests squarely on these three characteristics. From a systems perspective,
      the quality of primary care encompasses more than the right assortment of
      clinical competencies; quality has to be grounded in and realized at the
      individual level where physician and patient meet and interact over time. The
      discussion thus rests on the assumption that primary care is a process of care
      rather than a collection of skills. This study was stimulated by two factors: the
      claim of subspecialists to at times provide primary care and L. H. Aiken et al.'s
      article on the contribution of specialists to primary care. The author of the
      present article surveyed 467 internists and subspecialists and asked if they
      equated principal care with general internal medicine (IM) care-a primary care
      competency. The percentage of IM in their practice was also surveyed. The 160
      responses revealed that the percentage of subspecialist care to primary care was
      similar to that described in Aiken et al.'s article. The notion of principal care
      thus appears to better reflect the realities of clinical practice.

PMID- 8547797
TI  - Laparoscopic and open cholecystectomy outcomes in Medicare beneficiaries in
      member states of the Large State PRO Consortium.
AB  - To determine the incidence of laparoscopic cholecystectomy (LC) and open
      cholecystectomy (OC) and some of their possible outcomes (complications,
      mortality, 30-day readmission) in the general population of senior citizens, we
      examined Medicare claims data for beneficiaries 65 years and older in eight
      states. Billing data for all cholecystectomies (ICD9-CM 51.22, 51.23) performed
      on an inpatient basis in those states on Medicare beneficiaries age 65 and older
      during fiscal year 1992 were examined. The incidence of LC in each state ranged
      from 2.1 to 3.2/1,000, whereas the incidence of OC ranged from 2.2 to 3.5/1,000.
      Eleven and one-half percent of LC patients suffered at least one perioperative
      complications, as did 21.5% of OC patients. There was considerable interstate
      variation in complication rates. In-hospital mortality was about five times
      greater of OC (4.5%) than for LC (0.9%). Patients who underwent OC were more
      likely (9.2%) to be readmitted within 30 days than were LC patients (7.0%). LC
      seems to be at least as safe as OC in the elderly population. Analyzing Medicare
      claims data can be useful in uncovering geographic variations in cholecystectomy
      practice.

PMID- 8547798
TI  - Efficiency pattern analysis for medical rehabilitation.
AB  - Efficiency pattern analysis (EPA) is a technique proposed for use in medical
      rehabilitation that links patient functional gain to resource use, as
      approximated by length of stay (LOS), after adjusting for initial severity. The
      Functional Independence Measure version of the Function Relation Groups (FIM
      FRGs) is used to adjust for patient severity and to define the efficiency groups.
      The efficiency groups are based on LOS and functional gain cut point values in
      the statistical distribution that are above, below, or within the national
      interquartile range for each of 53 FRGs. Data from 32,494 patients discharged in
      1990 from 123 rehabilitation facilities were used. EPA is a simple way to monitor
      change in functional gain in response to transformations in health care practices
      and resource availability. The technique could also provide individual facilities
      with a means to evaluate treatment efficiencies across time and to compare
      patterns of LOS and functional gain to national norms.

PMID- 8547799
TI  - TeamWorks: a model for continuous quality improvement in the health care
      industry.
AB  - Total quality management (TQM) or continuous quality improvement (CQI) are terms
      no longer being used exclusively within the manufacturing industry sector. Health
      care facilities, such as hospitals and nursing homes, are beginning to actively
      compete with each other for patients as well as face new regulations from the
      government. Hence, it is imperative that these facilities reevaluate their
      services and correct any production problems in order to be cost-effective and
      efficient in providing quality. Therefore, the objective of this article is to
      describe a model developed for improvement of hospital-wide services provided by
      the Baptist Health Systems' Montclair facility, a private, community hospital
      located in Birmingham, Alabama. The TeamWorks for Quality model, used to charter
      over 40 teams, illustrates how managers and employees can build a multifaceted
      process that delivers services in excess of customer expectations.

PMID- 8547800
TI  - The effects of newborn early discharge on hospital readmissions.
AB  - The objective of this study is to determine the effects of early newborn hospital
      discharge policy on hospital readmission for Medicaid infants. It is a multiple
      year, retrospective study in which early hospital discharges were followed using
      Medicaid claims data to determine the rate of readmissions for newborns during
      1989-1992, the years in which this policy became widespread in Maryland. Analysis
      compares early discharges, using chi 2 tests, and calculates odds ratios to
      estimate the risk of readmissions. Our results found significant increases in
      early discharges for Medicaid newborns over time among sick newborns. The odds of
      readmissions for normal babies discharged early were about the same as for those
      kept longer, but for sick babies discharged early they were significantly
      greater, especially during the early study years. Findings from this natural
      experiment indicate that early discharge of Medicaid newborns with physical
      problems increases their likelihood of readmissions. Careful attention to the
      needs of these higher risk infants must be a part of any hospital or managed care
      program implementing early discharge policy.

PMID- 8547801
TI  - Ten tools of continuous quality improvement: a review and case example of
      hospital discharge.
AB  - Concepts and methods of continuous quality improvement have been endorsed by
      quality specialists in American Health care, and their use has convinced CEOs
      that industrial methods can make a contribution to health and medical care. For
      all the quality improvement publications, there are still few that offer a clear,
      concise definition and an explanation of the primary tools for teaching purposes.
      This report reviews ten continuous quality improvement methods including: problem
      solving cycle, affinity diagrams, cause and effect diagrams, Pareto diagrams,
      histograms, bar charts, control charts, scatter diagrams, checklists, and a
      process decision program chart. These do not represent an exhaustive list, but a
      set of commonly used tools. They are applied to a case study of bed utilization
      in a university hospital.

PMID- 8547802
TI  - Quality in the U.S. health care system.

PMID- 8547803
TI  - Quality in the U.S. health care system.

PMID- 8547804
TI  - Moving In.

PMID- 8547805
TI  - Marianne French Gonsalves: oncology nurse practitioner. Interview by Karna
      Bramble.

PMID- 8547806
TI  - Diet and development of cancer.

PMID- 8547807
TI  - An overview of childhood cancer.
AB  - The purpose of this article is to present information of interest to nurse
      practitioners on childhood cancer. It will begin with a brief review of the
      disease including details of incidence, morbidity, and mortality. Information on
      the clinical presentation, treatment methods, and prognosis of the most common
      forms is included. The paper concludes with a brief overview of selected issues
      related to this disease of interest to the primary care provider.

PMID- 8547808
TI  - Follow-up care for survivors of childhood cancer.
AB  - The number of survivors of childhood cancer is steadily increasing as the long
      term prognosis for cancer in children improves. As these patients reach
      adulthood, the need for continued follow-up related to the late effects of their
      cancer therapy is necessary. Such effects can occur in many body systems,
      although the cardiac effects of anthracyclines (doxorubicin and daunomycin Astra,
      USA Inc, West Borough, MA) are the most life threatening. It is important that
      survivors are educated about the treatments they received and that they and their
      health care providers are alert to the potential late effects.

PMID- 8547809
TI  - Cancer is a chronic disease.
AB  - Improved prevention and detection methods, as well as advances in medical
      treatment have resulted in a trend of increasing numbers of cancer survivors.
      Today, there are over 8 million cancer survivors, 5 million of whom were
      diagnosed 5 or more years ago. Cancer, once thought of as an acute disease, is
      increasingly being classified as a chronic disease. This article reviews
      physical, psychological, and social aspects of cancer survivorship, as well as
      other issues related to a diagnosis of cancer.

PMID- 8547810
TI  - The economic impact of cancer.
AB  - Primary care nurse practitioners will see more and more patients who survive
      cancer. This article describes the costs of cancer as a chronic disease and the
      related clinical issues, and recommends how nurse practitioners can be advocates
      for their patients politically, with insurance companies, and individually.

PMID- 8547811
TI  - Cancer in adults: a focus on prevention and detection in the nurse practitioner's
      practice.
AB  - This article provides a very general overview of the group of diseases called
      cancer. The clinical practice of the nurse practitioner emphasizes health
      maintenance and promotion of a healthy life style. This focus can carry over into
      the survival phase of the cancer experience. Counseling about risk status and
      risk reduction are an integral part of the total approach to cancer care. These
      activities can be integrated into standard care delivered by the nurse
      practitioner.

PMID- 8547812
TI  - Sex and sexuality in the cancer patient.
AB  - The number of cancer survivors is increasing dramatically. Advanced Practice
      Nurses (APNs) will have the opportunity to work with cancer survivors as part of
      their clinical practice and can have influence on the cancer survivor's sexuality
      as part of the normalization process. Consequently, the cancer survivor's journey
      will be much richer with an even greater potential for a better quality of life.

PMID- 8547813
TI  - Co-action between phytochrome B and HY4 in Arabidopsis thaliana.
AB  - A combination of physiological and genetic approaches was used to investigate
      whether phytochromes and blue light (BL) photoreceptors act in a fully
      independent manner during photomorphogenesis of Arabidopsis thaliana (L.) Heynh.
      Wild-type seedlings and phyA, phyB and hy4 mutants were daily exposed to 3 h BL
      terminated with either a red light (R) or a far-red light (FR) pulse. In wild
      type and phyA-mutant seedlings, BL followed by an R pulse inhibited hypocotyl
      growth and promoted cotyledon unfolding. The effects of BL were reduced if
      exposure to BL was followed by an FR pulse driving phytochrome to the R-absorbing
      form (Pr). In the wild type, the effects of R versus FR pulses were small in
      seedlings not exposed to BL. Thus, maximal responses depended on the presence of
      both BL and the FR-absorbing form of phytochrome (Pfr) in the subsequent dark
      period. Impaired responses to BL and to R versus FR pulses were observed in phyB
      and hy4 mutants. Simultaneous irradiation with orange light indicated that BL,
      perceived by specific BL photoreceptors (i.e. not by phytochromes), required
      phytochrome B to display a full effect. These results indicate interdependent co
      action between phytochrome B and BL photoreceptors, particularly the HY4 gene
      product. No synergism between phytochrome A (activated by continuous or pulsed
      FR) and BL photoreceptors was observed.

PMID- 8547814
TI  - Extension-growth responses and expression of flavonoid biosynthesis genes in the
      Arabidopsis hy4 mutant.
AB  - The hy4 mutant of Arabidopsis thaliana (L.) Heynh. was previously shown to be
      impaired in the suppression of hypocotyl extension specifically by blue light. We
      report here that hy4 is altered in a range of blue-light-mediated extension
      growth responses in various organs in seedlings and mature plants: it shows
      greater length of bolted stems, increased petiole extension and increased leaf
      width and area in blue light compared to the wild type. The hy4 mutant shows
      decreased cotyledon expansion in both red and blue light compared to the wild
      type. Anthocyanin formation and the expression of several flavonoid biosynthesis
      genes is stimulated by blue light in the wild type but to a much lower extent in
      hy4. The results indicate that the HY4 gene product is concerned with the
      perception of blue light in a range of extension-growth and gene-expression
      responses in Arabidopsis.

PMID- 8547815
TI  - Deletion analysis of the Brassica napus cruciferin gene cru 1 promoter in
      transformed tobacco: promoter activity during early and late stages of
      embryogenesis is influenced by cis-acting elements in partially separate regions.
AB  - To define sequences in the cruciferin gene cru1 promoter of importance for
      expression, tobacco (Nicotina tabacum L.) plants were transformed with constructs
      in which the cru1 promoter, in front of the intact cru1 structural gene, was
      truncated at -1216, -974, -736, -515, -306, -46 and -17 bp relative to the cap
      site. Cru1 expression in tobacco seeds was studied by Northern analysis, Western
      analysis and in-situ hybridizations. Comparisons of the Northern analysis of RNA
      from tobacco seeds harvested at 18 d after pollination with the Western analysis
      of protein from mature seeds showed that the regions between -974 to -736 and 
      306 to -46 were important for the expression of cru1 at an early developmental
      stage, whereas the regions -736 to -515 and -515 to -306 were important for
      expression throughout embryogenesis. By investigating the mRNA levels in
      transgenic seeds at different stages of development, indications were obtained
      that the two latter regions exerted their effects during the later stages. The in
      situ hybridization showed that cru1 mRNA was distributed in parenchyma cells
      throughout the embryo in seeds expressing constructs -974 and -736. Constructs 
      515 and -306 showed an expression restricted to the axis or axis and parts of the
      cotyledons. Sequence comparisons of the cru1 promoter with other storage-protein
      gene promoters, identified several motifs implicated in gene regulation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8547816
TI  - Endogenous gibberellin levels influence in-vitro shoot regeneration in
      Arabidopsis thaliana (L.) Heynh.
AB  - The regeneration of shoot buds from callus cells in vitro is an important
      technique in modern plant genetic manipulation. Whilst it is clear that genetic
      factors play a major role in determining the ability of callus cells to become
      organized into regenerating shoot buds, the precise nature of these factors
      remains unknown. Here we show that callus derived from mutants of Arabidopsis
      thaliana which have reduced levels of endogenous bioactive gibberellins (GAs), or
      reduced responsivity to GAs, regenerates shoot buds more readily than does callus
      derived from wild-type controls. In addition, exogenous GA reduces, and exogenous
      paclobutrazol (a GA-bio-synthesis inhibitor) increases, the frequency of shoot
      bud regeneration from wild-type callus. These results show that GA levels play a
      role in regulating shoot bud regeneration from callus, and suggest that variation
      in endogenous GA levels or responsivity may account for a major component of the
      genetic variation in shoot bud regeneration frequency described in other species.

PMID- 8547817
TI  - Acclimation of Arabidopsis thaliana to the light environment: changes in
      photosynthetic function.
AB  - Arabidopsis thaliana (L.) Heynh. cv. Landsberg erecta was grown under light
      regimes of differing spectral qualities, which results in differences in the
      stoichiometries of the two photosynthetic reaction centres. The acclimative value
      of these changes was investigated by assessing photosynthetic function in these
      plants when exposed to two spectrally distinct actinic lights. Plants grown in an
      environment enriched in far-red light were better able to make efficient use of
      non-saturating levels of actinic light enriched in long-wavelength red light.
      Simultaneous measurements of chlorophyll fluorescence and absorption changes at
      820 nm indicated that differences between plants grown under alternative light
      regimes can be ascribed to imbalances in excitation of photosystems I and II
      (PSI, PSII). Measurements of chlorophyll fluorescence emission and excitation
      spectra at 77 K provided strong evidence that there was little or no difference
      in the composition or function of PSI or PSII between the two sets of plants,
      implying that changes in photosynthetic stoichiometry are primarily responsible
      for the observed differences in photosynthetic function.

PMID- 8547818
TI  - Monocotyledonous C4 NADP(+)-malate dehydrogenase is efficiently synthesized,
      targeted to chloroplasts and processed to an active form in transgenic plants of
      the C3 dicotyledon tobacco.
AB  - Chloroplastic NADP(+)-malate dehydrogenase (cpMDH, EC 1.1.1.82) is a key enzyme
      in the carbon-fixation pathway of some C4 plants such as the monocotyledons maize
      or Sorghum. We have expressed cpMDH from Sorghum vulgare Pers. in transgenic
      tobacco (Nicotiana tabacum L.) (a dicotyledonous C3 plant) by using a gene
      composed of the Sorghum cpMDH cDNA under the control of cauliflower mosaic virus
      35S promoter. High steady-state levels of cpMDH mRNA were observed in isogenic
      dihaploid transgenic tobacco lines. Sorghum cpMDH protein was detected in
      transgenic leaf extracts, where a threefold higher cpMDH activity could be
      measured, compared with control tobacco leaves. The recombinant protein was
      identical in molecular mass and in N-terminal sequence to Sorghum cpMDH. The
      tobacco cpMDH protein which has a distinct N-terminal sequence, could not be
      detected in transgenic plants. Immunocytochemical analyses showed that Sorghum
      cpMDH was specifically localized in transgenic tobacco chloroplasts. These data
      indicate that Sorghum cpMDH preprotein was efficiently synthesized, transported
      into and processed in tobacco chloroplasts. Thus, C3-C4 photosynthesis
      specialization or monocotyledon-dicotyledon evolution did not affect the
      chloroplastic protein-import machinery. The higher levels of cpMDH in transgenic
      leaves resulted in an increase of L-malate content, suggesting that carbon
      metabolism was altered by the expression of the Sorghum enzyme.

PMID- 8547819
TI  - Glyoxysomal malate dehydrogenase and malate synthase from soybean cotyledons
      (Glycine max L.): enzyme association, antibody production and cDNA cloning.
AB  - In order to investigate a possible association between soybean malate synthase
      (MS; L-malate glyoxylate-lyase, CoA-acetylating, EC 4.1.3.2) and glyoxysomal
      malate dehydrogenase (gMDH; (S)-malate: NAD+ oxidoreductase, EC 1.1.1.37), two
      consecutive enzymes in the glyoxylate cycle, their elution profiles were analyzed
      on Superdex 200 HR fast protein liquid chromatography columns equilibrated in low
      and high-ionic-strength buffers. Starting with soluble proteins extracted from
      the cotyledons of 5-d-old soybean seedlings and a 45% ammonium sulfate
      precipitation, MS and gMDH coeluted on Superdex 200 HR (low-ionic-strength
      buffer) as a complex with an approximate relative molecular mass (Mr) of 670,000.
      Dissociation was achieved in the presence of 50 mM KCl and 5 mM MgCl2, with the
      elution of MS as an octamer of M(r) 510,000 and of gMDH as a dimer of M(r)
      73,000. Polyclonal antibodies raised to the native copurified enzymes recognized
      both denatured MS and gMDH on immunoblots, and their native forms after gel
      filtration. When these antibodies were used to screen a lambda ZAP II expression
      library containing cDNA from 3-d-old soybean cotyledons, they identified seven
      clones encoding gMDH, whereas ten clones encoding MS were identified using an
      antibody to SDS-PAGE-purified MS. Of these cDNA clones a 1.8 kb clone for MS and
      a 1.3-kb clone for gMDH were fully sequenced. While 88% identity was found
      between mature soybean gMDH and watermelon gMDH, the N-terminal transit peptides
      showed only 37% identity. Despite this low identity, the soybean gMDH transit
      peptide conserves the consensus R(X6)HL motif also found in plant and mammalian
      thiolases.

PMID- 8547820
TI  - Isolation and preliminary characterization of gas1-1, a mutation causing partial
      suppression of the phenotype conferred by the gibberellin-insensitive (gai)
      mutation in Arabidopsis thaliana (L.) Heyhn.
AB  - The semi-dominant gai mutation of arabidopsis confers a dark-green dwarf
      phenotype resembling that of gibberellin (GA)-deficient mutants. In contrast to
      GA-deficient mutants, gai mutants do not respond to GA treatments and accumulate
      higher levels of bioactive GAs than are found in wild-type controls. The gai
      mutation thus alters the responses of plant cells to GA, indicating that the GAI
      (wild-type) gene product is involved in GA reception and/or signal transduction.
      Here we describe the isolation and preliminary characterization of a mutation,
      gas1-1, which is not linked to gai and which partially suppresses the effect of
      the gai mutation. Double mutant, gai gas1-1, homozygotes are less severely
      dwarfed and lighter green than gai GAS1 controls. However, comparisons of the
      effects of treatments with exogenous GA demonstrate that gas1-1 does not increase
      the GA responsiveness of the gai mutant. Thus the gas1-1 mutation appears to
      reduce the GA-dependency of plant growth, and identifies a gene (GAS1) whose
      product is a candidate GA signal-transduction component.

PMID- 8547821
TI  - Cloning and characterisation of glutathione reductase cDNAs and identification of
      two genes encoding the tobacco enzyme.
AB  - We have isolated 4 cDNA clones (GRT1-4) encoding glutathione reductase (GR) from
      a tobacco (Nicotiana tabacum L.) leaf cDNA library. The cDNAs were almost
      identical: GRT1, GRT3 and GRT4 represented the same gene, differing only in that
      GRT4 contained an intron within the C-terminal part of the coding sequence.
      Failure to splice out this intron resulted in a substitution of the final 13
      amino acids of the deduced amino acid sequence. A second gene was represented by
      GRT2. Southern blots indicated that there were two related GR genes in tobacco.
      The presence of multiple isoforms of GR in tobacco may be explained in part by
      the expression of a small gene family. In addition, alternative isoforms may
      result from translation of different mRNAs derived from the same gene by intron
      skipping during the splicing of nascent GR mRNAs.

PMID- 8547822
TI  - The 4th American Cancer Society Award for Research Excellence in Cancer
      Epidemiology and Prevention. Phenotypes, Genotypes, and Interventions for
      Hereditary Cancers.

PMID- 8547823
TI  - A case-control study of wood dust exposure, mutagen sensitivity, and lung cancer
      risk.
AB  - The associations between lung cancer risk, mutagen sensitivity (a marker of
      cancer susceptibility), and a putative lung carcinogen, wood dust, were assessed
      in a hospital-based case-control study. There were 113 African -American and 67
      Mexican-American cases with newly diagnosed, previously untreated lung cancer and
      270 controls, frequency-matched on age, ethnicity, and sex. Mutagen sensitivity (
      1 chromatid break/cell after short-term bleomycin treatment) was associated with
      statistically significant elevated risk for lung cancer [odds ration (OR) = 4.3;
      95% confidence intervals (CI) = 2.3-7.9]. Wood dust exposure was also a
      significant predictor of risk (overall OR = 3.5; CI = 1.4-8.6) after controlling
      for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust
      exposure was s significant risk factor for African-Americans (OR = 5.5; CI = 1.6
      18.9) but not for Mexican-Americans (OR = 2.0; CI = 0.5-8.1). The ORs were 3.8
      and 4.8 for non-small cell lung cancer in Mexican-Americans (CI = 1.2-18.5).
      Stratified analysis suggested evidence of strong interactions between wood dust
      exposure and both mutagen sensitivity and smoking in lung cancer risk.

PMID- 8547824
TI  - Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk.
AB  - The association between glutathione S-transferase M1 (GSTM1) deficiency and lung
      cancer risk has been controversial in the published literature. To examine this
      controversy, 12 case-control studies of GSTM1 status and lung cancer risk were
      identified in the published English literature. These studies included a total of
      1593 cases and 2135 controls. We conclude that GSTM1 deficiency is a moderate
      risk factor for lung cancer development with an odds ratio of 1.41 (95%
      confidence interval = 1.23-1.61; P < 0.0001) by using Mantel-Haenszel methods for
      stratified analysis. This increased risk is evident for all the major
      histological subtypes of lung cancer. Although the increased risk is small, GSTM1
      deficiency accounts for approximately 17% of lung cancer cases because of the
      high prevalence of GSTM1 deficiency.

PMID- 8547825
TI  - Hot and cold mate drinking and esophageal cancer in Paraguay.
AB  - A hospital-based case-control study, including 131 cases of esophageal cancer and
      381 controls, was carried out in Paraguay to investigate the role of hot and cold
      mate drinking in esophageal cancer risk. Detailed information on mate drinking
      and on tobacco smoking, alcohol consumption, and dietary habits was obtained by
      interview. Amount and duration of cold or hot mate drinking were not associated
      with esophageal cancer risk. However, temperature at which mate was drunk was
      significantly associated with risk. As compared to drinkers of warm or hot mate,
      drinkers of very hot mate had an increased risk for esophageal cancer even after
      adjusting for the strong effects of alcohol and tobacco consumption (adjusted
      odds ratio = 2.4; 95% confidence interval = 1.3-4.3). This effect seemed to be
      mainly due to the temperature at which mate cocido (one of the two ways in which
      hot mate is prepared) was drunk (odds ratio = 6.5; 95% confidence interval = 3.2
      12.2). As expected, very strong dose-response associations were found for alcohol
      consumption and cigarette smoking. After correcting for these and the consumption
      of other food groups, diets rich in fats and red meats, especially beef, were
      associated with esophageal cancer risk. In conclusion, the findings from this
      study suggest that cold mate drinking does not increase the risk of esophageal
      cancer. This study identifies the very hot temperature at which mate is drunk,
      and not the amount or the duration, as an important risk factor for esophageal
      cancer in this population. Alcohol drinking and tobacco smoking remain,
      nevertheless, the main risk factors for esophageal cancer in Paraguay.

PMID- 8547826
TI  - Cytochrome P4502E1 genetic polymorphisms and risk of nasopharyngeal carcinoma:
      results from a case-control study conducted in Taiwan.
AB  - CYP2E1 is responsible for the metabolic activation of nitrosamines believed to be
      involved in the pathogenesis of various tumors. Nasopharyngeal carcinoma (NPC) is
      a tumor thought to be linked to nitrosamine exposure. To investigate the possible
      role of CYP2E1 genetic polymorphisms in the etiology of this tumor, we
      investigated 50 histologically confirmed NPC cases from Taiwan and 50 controls
      matched to cases on age, sex, and residence. Samples were examined for RFLPs in
      the CYP2E1 gene by PCR amplification followed by digestion with DraI and RsaI.
      Among healthy controls, the allelic frequency of wild-type and variant forms of
      CYP2E1 were 79 and 21%, respectively, using DraI enzyme digestion and 82 and 18%,
      respectively, using RsaI enzyme digestion. As compared with individuals who were
      homozygous for the wild-type CYP2E1 gene, those found to be homozygous for the
      variant form of the gene by DraI digestion were at a 5-fold excess risk of
      disease (95% confidence interval = 0.95-16). Similarly, subjects homozygous for
      the variant form of the CYP2E1 gene by RsaI digestion were at 7.7-fold excess
      risk of developing NPC (95% confidence interval = 0.87-68). Individuals found to
      be heterozygous for the gene were at similar risk of disease compared to those
      homozygous for the wild-type gene. A strong association was observed between the
      RFLPs detected by DraI and RsaI digestion of CYP2E1; a correlation coefficient of
      0.86 for controls and 0.91 for cases was observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8547827
TI  - Heart rate and prostate cancer mortality: results of a prospective analysis.
AB  - Recent studies suggest that local levels of sympathetic nervous activity
      influence the growth of prostatic tissue. In several epidemiological studies,
      resting heart rate, an indicator of overall sympathetic activity, was positively
      associated with all noncardiovascular and cancer death among men. However, no
      previous analyses have focused on the specific relationship of heart rate to
      prostate cancer mortality. We studied 22,380 men enrolled in the Chicago Heart
      Association cohort from 1967-1973, who had heart rate (HR) determined by
      electrocardiogram. Mean length of follow-up (for mortality) was 19.2 years. We
      computed age-adjusted rates for prostate cancer death by variable of interest and
      fitted proportional hazards models to estimate relative risks (RRs) adjusted for
      potential confounders. In a model controlling for age, body mass index, blood
      pressure, serum cholesterol, smoking, postload plasma glucose, and years of
      education, the RR for a 10 beat/min higher HR was 1.26 (95% confidence interval =
      1.04-1.51). Age-adjusted RRs across higher quintiles for HR were 1.00, 1.55,
      1.85, 2.18, and 2.69 (P trend = 0.006). Survival curves indicated that the
      elevated risk was not confined to the early years of follow-up. Because little is
      known about factors that determine risk of prostate cancer death, these results
      could prove important even if due to an unmeasured etiological factor other than
      heart rate itself. The results are consistent with the hypothesis that local
      neurotrophic factors associated with sympathetic activity influence the
      progression of prostate cancer

PMID- 8547828
TI  - Variation in the expression of p53, c-myc, and bcl-2 oncoproteins in individual
      patient cultures of normal urothelium exposed to cobalt 60 gamma-rays and N
      nitrosodiethanolamine.
AB  - The controls determining the initial response of cells to DNA damage probably
      determine whether a cancer will ultimately occur. Efficient repair or apoptosis
      represents extremes of control mechanisms. Misrepair can lead to fixation of
      damage. The changes in oncoprotein expression of three genes involved in the
      regulation of repair of DNA damage and postdamage proliferation of cells were
      measured in cultures of normal urothelium from 55 patients without any
      malignancy. The aim was to obtain information on interperson variation in
      response to carcinogens in the human population. The group included 10 pediatric
      patients < 2 years old. Two different carcinogenic agents, ionizing radiation and
      N-nitrosodiethanolamine, which represent widely different DNA-damaging pathways,
      were used. Both of these cause bladder cancer in humans. Cells from explanted
      tissue were examined after carcinogen exposure for levels of p53, c-myc, and bcl
      2 proteins. Both carcinogens led to increased levels of cytoplasmic p53 protein
      expression, although there was significant interpatient variation. bcl-2 showed a
      very significant increase in expression after radiation exposure. c-myc was high
      and variable pre- and postexposure. Individual patient culture changes in the
      expression of the three oncoproteins did not correlate significantly with each
      other or with cell growth, suggesting that the controls are complex. Pediatric
      samples had lower mean control values of p53 and bcl-2 than did adult samples.
      This was due to the absence in this group of high controls seen in some adult
      cultures. The result suggest that an early breakdown in control mechanisms of
      growth arrest and apoptosis may occur in urothelium after carcinogen
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547829
TI  - Decline of DNA damage and other biomarkers in peripheral blood following smoking
      cessation.
AB  - Serial samples from 40 heavy smokers ( > or = pack/day for > or = 1 year)
      enrolled in a smoking cessation program were assayed for cotinine, polycyclic
      aromatic hydrocarbon (PAH)-DNA, 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts,
      and glycophorin A (GPA) mutations. Blood samples were taken while subjects were
      smoking, and 10 weeks and 8 and 14 months after quitting. Cotinine was used to
      assess compliance with the cessation protocol. A significant reduction in mean
      PAH-DNA and 4-ABP-Hb adducts was observed after cessation in all persons who were
      cotinine-verified quitters ( < or = 25 ng/ml) for > or = 8 months (P < 0.05).
      Neither the GPA N/phi nor the GPA N/N mutation Vf was significantly reduced after
      smoking cessation, but results are limited by the small number (n = 18) of
      heterozygous individuals studied. The substantial reduction (50-75%) in PAH-DNA
      and 4-ABP-Hb adduct levels after quitting indicates these carcinogen adducts are
      reflective of smoking. Passive exposure to smoke at home was significantly
      associated with PAH-DNA adducts in active smokers and in ex-smokers 10 weeks
      after quitting (P < 0.01). The estimated half-life of the PAH-DNA adducts in
      leukocytes is 9-13 weeks by inspection of the mean biomarker levels from baseline
      and 10 weeks sample and 23 (95% confidence interval, 10-36 weeks) using a linear
      regression model that adjusted for background.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547830
TI  - Intraindividual and interindividual differences in metabolites of the tobacco
      specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in
      smokers' urine.
AB  - This study describes quantitation in smokers' urine of two metabolites of the
      tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK). The metabolites are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL),
      which is also a lung carcinogen, and its O-glucuronide (NNAL-Gluc), a presumed
      detoxification product of NNK. Using updated methodology, levels of NNAL, NNAL
      Gluc, and cotinine were determined in the urine of 61 smokers. The NNAL-Gluc:
      NNAL ratio, a potential marker for NNK detoxification potential, varied 16-fold
      in this group. Two phenotypes of this ratio were apparent; one ranging from 0 to
      6 and found in 85% of the smokers and a second ranging from 6 to 11. The short
      term and long-term consistency of the ratio was investigated. Studies carried out
      over a 4-5 day period indicated that the NNAL-Gluc: NNAL ratio was reasonably
      stable. Subjects who donated urine samples on two occasions separated by 4-16
      months were classified in the same group (ratio range, 0-6 or 6-11) each time.
      Different urine collection protocols appeared to have little influence on the
      NNAL-Gluc: ratio. Thus, intraindividual differences in the NNAL-Gluc:NNAL ratio
      were generally small, whereas interindividual differences were large. Amounts of
      NNAL, NNAL-Gluc, and cotinine excreted by smokers were constant in 24-h samples
      obtained over a 3-day period of constant cigarette intake and controlled diet.
      Levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc correlated with cotinine in a
      study of 61 smokers without controlled diet or smoking (r = 0.58; P <
      0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547831
TI  - Noninvasive detection of putative biomarkers for colon cancer using fecal
      messenger RNA.
AB  - Deaths from colon cancer number over 60,000 each year in the United States.
      Because early detection results in a high cure rate, development of noninvasive
      techniques for detection of colon cancer has received much interest. The ability
      to detect early changes in colonocyte genes and gene expression would provide
      valuable information. We have shown previously that alterations in protein kinase
      C (PKC) isoform expression are associated with changes in colonic cell
      proliferation, a key intermediate marker for the prediction of tumorigenesis.
      Here, we describe a method for the quantitative detection of mRNAs for select PKC
      isoforms isolated from rat feces containing exfoliated colonocytes. After total
      RNA extraction from fresh fecal material, polyadenylated RNA was selectively
      purified and quantitated with slot blotting and hybridization to
      oligodeoxythymidylic acid. Fecal polyadenylated RNA was used for semiquantitative
      (mimic) RT-PCR to quantitate PKC isoform mRNA expression. We detected mRNA for
      PKC-alpha, PKC-delta, PKC-epsilon, and PKC-sigma, but not for PKC-beta or PKC
      gamma, which is consistent with the profile of isoforms detected previously in
      scraped colonic mucosa using immunoblot analysis. This noninvasive method,
      utilizing feces containing exfoliated colonocytes, is a sensitive noninvasive
      technique for quantitating luminal mRNAs. This provides a means to monitor gene
      expression of colonic epithelial cells, which may have predictive value in
      monitoring the neoplastic process.

PMID- 8547832
TI  - Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year
      period.
AB  - We evaluated the reproducibility of plasma hormone levels over time in 79 healthy
      postmenopausal women, ages 51-69 years at baseline, who were not using
      postmenopausal hormones. Three blood samples were collected between 1989 and 1992
      from each of these women. We assessed plasma levels of estradiol, free estradiol,
      percentage of free estradiol, bioavailable estradiol, percentage of bioavailable
      estradiol, estrone, estrone sulfate, sex hormone-binding globulin (SHBG),
      androstenedione, testosterone, dehydroepiandrosterone, dehydroepiandrosterone
      sulfate, and prolactin at each of three sample collections. The means and SD for
      each of the plasma estrogens, SHBG, and prolactin were similar at each
      collection. For the androgens, plasma levels tended to decrease over time
      consistent with an aging effect; decreases with increasing age were statistically
      significant for androstenedione, dehydroepiandrosterone, and
      dehydroepiandrosterone sulfate. Intraclass correlation coefficients (ICCs) ranged
      from 0.92 (95% confidence interval = 0.89-0.95) for SHBG to 0.53 (95% confidence
      interval = 0.43-0.69) for prolactin. Most correlations were at least 0.70. The
      ICCs did not vary by age or time since menopause. Women who changed weight over
      the course of the study tended to have lower ICCs for a number of the hormones,
      although these differences were not statistically significant. These data
      indicate that, for most of these plasma hormones, a single measurement can
      reliably categorize average levels over at least a 3-year period in
      postmenopausal women.

PMID- 8547833
TI  - Seasonal variation in vitamin D, vitamin D-binding protein, and
      dehydroepiandrosterone: risk of prostate cancer in black and white men.
AB  - Our previous study provided evidence that higher serum levels of the active form
      of vitamin D, 1,25-dihydroxyvitamin D (1, 25-D), might possibly slow the
      progression of subclinical to clinically significant prostate cancer in both
      black and white men, especially after age 57. This paper extends the prior study
      by contrasting seasonal variation in 1,25-D and its precursor, 25-hydroxyvitamin
      D (25-D), in case and control subjects. In addition, the risk of prostate cancer
      is related to serum levels of vitamin D-binding protein (VDBP) and total
      dehydroepiandrosterone and to polymorphic variation in VDBP. The expected
      elevated summer levels of 25-D were seen in case and control subjects and, as
      expected, 1,25-D did not vary throughout the year in the control subjects.
      Unexpectedly, lower case levels of 1,25-D were limited largely to the summer
      months (P = 0.01) in both black and white cases and to cases greater than or
      equal to the median age of 57 years. Levels of VDBP and dehydroepiandrosterone
      and the frequencies of VDBP polymorphisms were similar in case and control
      subjects, although striking differences were seen in allelic frequencies in black
      and white men. These observations provide additional evidence that vitamin D
      metabolism may impact the risk of prostate cancer.

PMID- 8547834
TI  - Design and recruitment for retinoid skin cancer prevention (SKICAP) trials. The
      Southwest Skin Cancer Prevention Study Group.
AB  - The retinoid skin cancer prevention (SKICAP) trials are a set of double-blind,
      randomized, placebo-controlled clinical trials. The SKICAP-actinic keratoses (AK)
      trial tests the hypothesis that daily supplementation of retinol (25,000 IU) for
      5 years reduces the incidence of skin cancers in high-risk individuals, those
      with a history of greater than ten clinically or pathologically diagnosed AK and,
      at most, one prior pathologically confirmed cutaneous squamous cell carcinoma
      (SCC) or basal cell carcinoma (BCC). The SKICAP-SCC/BCC (S/B) trial tests the
      hypothesis that daily supplementation of retinol (25,000 IU) or 13-cis-retinoic
      acid (5 or 10 mg) for 3 years reduces skin cancer incidence in very high-risk
      individuals, those with a history of at least four pathologically confirmed SCCs
      or BCCs. Between 1984 and 1988, 2800 participants were enrolled at two clinics on
      the SKICAP-AK trial; and between 1985 and 1990, a total of 719 participants were
      enrolled at four clinics on the SKICAP-S/B trial. The initial recruitment
      strategy was referral by dermatologists, but low accrual necessitated the use of
      other strategies to achieve enrollment goals, which included involving additional
      clinics and using paid trial-specific advertisements in print and electronic
      media. Thirteen % of the SKICAP-AK participants and 36% of the SKICAP-S/B
      participants were enrolled through dermatologist referral, whereas paid
      advertisements resulted in enrollment of 87% of SKICAP-AK and 43% of SKICAP-S/B
      participants. A population-based skin cancer registry was used to identify and
      enroll the remaining 21% of the SKICAP-S/B participants.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8547835
TI  - Influence of sex on cytogenetic end points: evidence from a large human sample
      and review of the literature.
AB  - The planning and evaluation of human cytogenetic studies should contemplate
      various confounders and effect modifiers, among these, sex and sex-related
      factors. The association between this variable and cytogenetic damage has been
      extensively studied, but conclusive evidence has thus far not been reached,
      especially for the most recent assays, such as the micronucleus test (MN). In the
      attempt to quantitatively estimate the sex effect on sister chromatid exchange
      (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we
      reanalyzed the original data sets of several biomonitoring studies performed over
      the last decades in 10 Italian laboratories. This approach yielded a very large
      database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN,
      respectively. Differences between sexes were expressed in terms of relative risk
      (RR) of females versus males, after adjustment for age, smoking habits,
      occupation exposure and inter- and intralaboratory variation. No difference
      between sexes was found for the frequency of SCE [RR = 1.01; 95% confidence
      interval (CI) = 0.99-1.03] and CA (RR = 1.00; 95% CI = 0.92-1.08) even if the CI
      of the RR for SCE includes the 3% excess in females frequently reported by the
      literature. Conversely, a 29% overall increase of the MN rate in females was
      observed in the whole data set (RR = 1.29; 95% CI = 1.20-1.38). Different trends
      by age of the MN rate are described in the two sexes, focusing on the peak
      observed in females in the menopausal period and on the subsequent decrease.

PMID- 8547836
TI  - Genetic characteristics of prostate cancer.
AB  - Prostate cancer is the most commonly diagnosed malignancy in united States males.
      Unfortunately, numerous controversies surround clinical management for early
      stage disease and the utility of population screening. Much of this controversy
      stems from the lack of knowledge about the biology of prostate cancer, including
      the lack of clearly defined risk factors, absence of markers indicative of
      aggressive clinical behavior, as well as a lack of a clear understanding of its
      underlying genetic features. This paper reviews currently available evidence
      regarding the genetic characteristics of adenocarcinoma of the prostate,
      including the impact of family history of disease risk, the nature of structural
      genetic aberrations, and the possible role of oncogenes and tumor suppressor
      genes in its pathogenesis. A clearer understanding of these issues will hopefully
      lead to more effective and rational treatment policies in addition to the
      development of effective disease prevention strategies.

PMID- 8547837
TI  - [Oxidases bd and bo as primary photoacceptors during exposure to low intensity
      visible monochromatic irradiation of Escherichia coli cells].

PMID- 8547838
TI  - [Various effects of continuous and pulsed laser irradiation (lambda=632.8 nm) on
      the oxidative metabolism of splenocytes].

PMID- 8547839
TI  - [Drosophila retrotransposon suffix has an ancient domain and fulfills a noncoding
      and coding function in the nucleus and cytoplasm in a different orientation].

PMID- 8547840
TI  - [Microstructure of the epithelial surface in the digestive tract of the yellow
      pawed squirrel (Gallosciurus flavimanus (I. Geoffroy, 1831), Rodentia,
      Mammalia)].

PMID- 8547841
TI  - Systematization of academic and scientific affiliation, or how to prevent data on
      your publications from being lost in the national and international data base.

PMID- 8547842
TI  - Calpain activity of hypertrophic hearts from hypertensive rats.
AB  - Heart tissue contains large amounts of the Ca(2+)-activated proteinase calpain
      which has been assigned a specific function in the turnover of muscle protein.
      The objective of the present study was to determine calpain (E.C. 3.4.22.17)-like
      activity in homogenates of left ventricle from hypertensive rats that developed
      ventricular hypertrophy. Calpain activity was assayed using heat-denatured
      azocasein as a substrate in the presence of 1 mM calcium and corrected by
      subtraction of the Ca(2+)-independent activities. The latter were measured in the
      presence of 1 mM EGTA and the products read at 440 nm. Male Wistar rats (225 g)
      were assigned to control (N = 8, normal drinking water), salt (N = 6, drinking
      water containing 1% NaCl) and DOCA-salt (N = 6, deoxycorticosterone acetate, 8
      mg/kg, sc, twice a week for 20 days plus drinking water containing 1% NaCl)
      groups. SHR (N = 6, spontaneously hypertensive rats) were also used. The calpain
      activity of the control group was at 3.90 +/- 0.22 mU/g wet weight tissue.
      Hypertension induced significant left ventricular hypertrophy in DOCA-salt rats
      (26%) and in SHR (54%) and a 30% decrease in calpain activity in both groups (P <
      0.01). In the high salt load (salt group) calpain activity was also decreased,
      but this was not accompanied by hypertrophy. In the present indirect measurement
      of protein degradation capacity of heart tissue homogenates the proteolytic
      activity was activated (221%) by 1 mM calcium and inhibited (84%) by 1 mM EGTA
      after a 48-h incubation period, indicating the destruction of the calpain
      inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547843
TI  - The role of antigenically different virus neuraminidases as structures implicated
      in receptor-binding processes.
AB  - Influenza A viruses exhibit segmented nucleic acid coding for eight different
      proteins, two of them as glycoproteins exposed on their lipoprotein envelopes,
      hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin exhibits receptor
      binding activity while neuraminidase develops sialidase cleavage activity which
      acts on cell receptors. Influenza A strains responsible for human, avian, equine
      and porcine respiratory infections all over the world present antigenically
      different hemagglutinin (H1 to H14) and neuraminidase (N1 to N9) structures on
      their surface. The objective of the present investigation was to study the role
      of N2, N8, and N9, antigenically diverse neuraminidase structures of human (N2)
      and animal (N8 and N9) influenza viruses, in the receptor-binding process.
      Receptor-binding activity of N2 and N8 was analyzed by crossed tests using H3N2
      and H3N8 antisera and the hemagglutination inhibition test as a model.
      Hemagglutinating activity of antigenically different N2 and N8 structures was
      demonstrable and was inhibited by homologous antisera (N2-H3N2, N8-H3N8) but not
      by heterologous antisera (N2-H3N8,N8-H3N2). This previously demonstrated N9
      hemagglutinating activity was analyzed for receptor-binding specificity using
      hemagglutination tests and NeuAc alpha2,3Gal and NeuAc alpha2,6Gal derivatized
      erythrocytes. This highly purified N9 strain was obtained from a virus strain
      isolated from terns by Dr. Peter Colman (CSIRO Division of Biomolecular
      Engineering, Parkville, Victoria, Australia). It exhibited receptor-binding
      specificity for NeuAc alpha2,3Gal sequences, a property similar to that observed
      in hemagglutinins from avian strains. These results indicate the importance of
      antigenically different neuraminidase structures as alternative agents for
      developing receptor-binding activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547844
TI  - Monoclonal antibodies specific for the free alpha subunit of glycoprotein
      hormones and their use in the development of a sensitive immunofluorometric
      assay.
AB  - Glycoprotein hormone free alpha subunit has been used as a marker for some
      pituitary tumors and to study the reactivity of glycoprotein hormone-producing
      cells under different circumstances. We describe a highly sensitive and specific
      immunofluorometric assay for the measurement of serum free alpha subunit levels.
      The assay is based on a monoclonal antibody, specific for free alpha subunit,
      bound to microtiter plates. As tracer antibody we employed an europium-labelled
      free/complexed alpha subunit specific monoclonal antibody. Using overnight
      incubation and 50-microliters samples, the least detectable dose was of the order
      of 4 ng/l. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%,
      respectively. Normal adult males showed values ranging from 120 to 790 ng/l, not
      different from normal adult premenopausal females (88 to 604 ng/l). In post
      menopausal females, serum concentrations were significantly higher, ranging from
      341 to 4071 ng/l. In 56 patients with untreated pituitary tumors (18 "non
      secreting", 25 GH-producing and 13 prolactin-producing tumors), 10 showed high
      values, 3 of them from the first group, 3 from the second and 4 from the third.
      We conclude that this highly sensitive assay can be a valuable tool for the
      diagnosis and follow-up of selected patients with pituitary tumors and in other
      circumstances in which the glycoprotein hormone-producing cells of the pituitary
      require evaluation.

PMID- 8547845
TI  - Beneficial effect of long-term use of a beta-blocker in patients before acute
      myocardial infarction.
AB  - The outcome of 38 beta-blocker users (group BB, 28 men and 10 women with a mean
      age of 56 +/- 4 years) was compared to that of 100 non-users (group NU, 69 men
      and 31 women with a mean age of 57 +/- 8 years) after acute myocardial infarction
      (AMI). The two groups were compared in terms of electrocardiographic (EKG)
      location of the AMI (anterior, inferior and lateral), EKG Q and non-Q wave
      infarction, clinical functional class of Forrester, serum creatine phosphokinase
      MB fraction (CKMB) peak release and intrahospital mortality. There were no
      differences between groups concerning sex or severity of coronary artery disease
      but arterial hypertension was 2-fold more prevalent in group BB. The EKG location
      of the AMI was similar in the two groups. Non-Q infarction was significantly more
      prevalent in group BB (37%) than in group NU (6%). The incidence of clinical
      functional class IV of Forrester and the serum CKMB peaks were significantly
      lower in group BB (2.6% vs 16.0% and 53 +/- 3 vs 68 +/- 9 IU/l, respectively).
      Intrahospital mortality was also significantly lower in group BB (2.6%) than in
      group NU (10%). These data suggest the beneficial effect of previous long-term
      use of beta-blockers as indicated by a lower incidence of cardiogenic shock and a
      significant decrease in intrahospital mortality after AMI.

PMID- 8547846
TI  - ATP diphosphohydrolase activity in synaptosomes from cerebral cortex of rats
      subjected to chemically induced phenylketonuria.
AB  - ATP diphosphohydrolase (apyrase) (EC 3.6.1.5) activity was measured in
      synaptosomes from cerebral cortex of Wistar rats of both sexes subjected to
      experimental phenylketonuria, i.e., chemical hyperphenylalaninemia induced by
      subcutaneous administration of 5.2 mumol phenylalanine/g body weight (twice a
      day) plus 0.9 mumol p-chlorophenylalanine/g body weight (once a day). ATP
      diphosphohydrolase specific activity (nmol Pi min-1 mg protein-1) of synaptosomes
      was significantly decreased compared to controls for both ATP (from 147.6 to
      129.9) and ADP (from 70.2 to 63.1) hydrolysis one hour after single
      administration of the drugs to 35-day old rats. Chronic treatment was performed
      from the 6th to the 28th postpartum day. The enzyme specific activity of
      synaptosomes was measured one week after the last administration of the drugs and
      was significantly reduced compared to controls for both ATP (from 164.1 to 150.2)
      and ADP (from 76.3 to 62.1) hydrolysis. The in vitro effects of the drugs on the
      synaptosome enzyme specific activity were also investigated. Phenylalanine alone
      or associated with p-chlorophenylalanine significantly reduced enzyme specific
      activity for both ATP (from 150.2 to 136.0) and ADP (from 70.5 to 59.3)
      nucleotides as substrates. Since ADP diphosphohydrolase seems to play an
      important role in neurotransmission, these findings may be related to the
      neurological dysfunction characteristic of human phenylketonuria.

PMID- 8547848
TI  - Studies of natural killer cells in pregnancy-induced hypertension.
AB  - The number and activity of natural killer (NK) cells were studied in 20 patients
      with pregnancy-induced hypertension (PIH), 15 uncomplicated pregnant women and 16
      healthy non-pregnant women. All the pregnant women were primigravidae and were
      evaluated during the third trimester of gestation. Peripheral blood NK cells were
      detected with monoclonal antibodies by indirect immunofluorescence and cytotoxic
      activity was measured using a single-cell assay against K562 target cells.
      Hypertensive pregnant women had an increased number of circulating NK cells
      associated with a significant decrease of NK activity. The cytotoxic activity was
      significantly lower in normal pregnant and PIH women when compared with non
      pregnant controls. The onset of immature NK cells in peripheral blood and the
      impairment of their cytotoxic activity in PIH patients may be associated with
      hormones and immunosuppressive substances produced by tissues occurring at the
      maternal-fetal interface.

PMID- 8547849
TI  - Is perinatal picrotoxin anxiogenic?
AB  - Female Wistar rats were exposed to a subconvulsant dose of picrotoxin (0.75
      mg/kg, sc) on day 18 of pregnancy, immediately after parturition and daily during
      the first 5 days of lactation. In adulthood, the offspring were tested in an open
      field, in an elevated plus maze and for social interaction. Results showed
      increased locomotor activity (75 days of age) and decreased social interaction
      (90 days of age) in experimental male rats compared to control male rats. No
      effects on behaviors related to anxiety were observed in males or females tested
      in the plus maze apparatus. An additional comparison of the activity of male and
      female animals perinatally treated with picrotoxin showed a lack of the classical
      sexual dimorphic responses in the open-field (control male = 68.7 +/- 6.31;
      control female = 98.4 +/- 6.31; experimental male = 89.6 +/- 6.32; experimental
      female = 113.2 +/- 4.74). We suggest that perinatal picrotoxin exposure may
      interfere with normal male masculinization rather than increasing anxiety in male
      rats.

PMID- 8547847
TI  - Determination of the efficiency of K99-F41 fimbrial antigen vaccine in newborn
      calves.
AB  - Semipurified K99 and F41 fimbrial antigens were used to prepare an oil-emulsified
      vaccine against bovine enterotoxigenic colibacillosis. Nine Nelore cows about 7
      months pregnant were divided into 3 groups (A, B and C) of 3 animals each, which
      received different doses of vaccine (1,500 HU, 750 HU and 380 HU, respectively) 8
      and 2 weeks before delivery, in the neck by the subcutaneous route. As a control
      (group D), 3 pregnant cows of the same breed were not vaccinated for later
      challange of their calves. Vaccine efficiency was measured by the serological
      tests double diffusion and ELISA. Challenge of calves from the vaccinated and
      from the three control unvaccinated cows was carried out with the virulent
      Escherichia coli B41 strain (0101, STa+, K99+, F41+). Two of the 3 calves from
      the unvaccinated cows died within 48 h with acute diarrhea. E. coli B41 was
      recovered as pure culture from their stools. In contrast, none of the calves born
      from vaccinated cows presented diarrhea. These data suggest that the antibody
      transfer to calves through colostrum gave full protection against the challenge.
      This semipurified fimbrial vaccine against K99-F41-harboring strains is the first
      oil-emulsified immunogen prepared in Brazil, which was not only efficient, but
      also had no adverse effects on vaccinated pregnant cows.

PMID- 8547850
TI  - The behavioral sensitization induced by fencamfamine is not related to plasma
      drug levels.
AB  - Fencamfamine (FCF) is a CNS stimulant that facilitates central dopaminergic
      transmission primarily through blockade of dopamine uptake. In the present study
      we evaluated the relationship between plasma FCF concentration and behavioral
      sensitization effect. Adult male Wistar rats (250-300 g) received FCF (10 mg/kg,
      ip) or saline once or daily for 10 consecutive days (N = 10 for each group).
      Blood samples were collected 30 min after injections and plasma FCF was measured
      by gas chromatography using an electron capture detector. FCF treatment enhanced
      sniffing duration (16.8 +/- 0.8 vs 26.6 +/- 0.9 s) and decreased rearing behavior
      (8.2 +/- 0.8 vs 3.7 +/- 0.6 s) when days 1 and 10 of drug administration were
      compared. Comparison of pair of means by the Student t-test did not show
      significant differences in plasma FCF concentration (390 +/- 40 vs 420 +/- 11
      ng/ml) when blood samples were collected 30 min after acute FCF administration or
      after daily administration of 10 mg/kg for 10 days. In conclusion, the behavioral
      sensitization to FCF could not be correlated with plasma drug levels, and changes
      in the activity of dopaminergic systems should be considered to explain the
      sensitization to the effect of FCF.

PMID- 8547851
TI  - Tumor necrosis factor accounts for the neutrophil emigration activity released by
      cultured malignant fibrous histiocytoma cells.
AB  - Cultured malignant fibrous histiocytoma (MFH) cells obtained from a spontaneous
      and transplantable rat tumor were studied for their ability to release tumor
      necrosis factor (TNF) and a factor which induces neutrophil migration in vivo.
      MFH cells obtained from 7-day cultures spontaneously released both activities
      into the supernatant (TNF: 36 +/- 9 IU TNF/ml supernatant, N = 3; neutrophil
      chemoattractant factor: control, Medium ip: 6 +/- 1 x 10(6); MFH supernatant: 18
      +/- 1 x 10(6) neutrophils/cavity, N = 5). These releases were enhanced by
      treating MFH cells with LPS (TNF: 61%; neutrophil chemoattractant factor: 46%)
      and were abolished by the glucocorticoid dexamethasone (TNF: 68%; neutrophil
      chemoattractant factor: 100%). Anti-TNF antiserum abolished the neutrophil
      chemoattractant activity of the supernatants (95%). The release of TNF or
      neutrophil chemoattractant activity was reduced in cells obtained from older
      cultures (14 and 21 days) (TNF: 7-day culture, 36 +/- 9; 14-day culture, 19 +/-
      2; 21-day culture, 19 +/- 1 IU of TNF/ml; neutrophil chemoattractant activity: 7
      day culture, 18 +/- 1.6; 14-day culture, 13 +/- 3; 28-day culture, 8 +/- 1 x
      10(6) neutrophils/cavity). The predominant cells present in 7-day cultures of MFH
      were histiocyte-like cells as determined by nonspecific esterase methods. The
      number of these cells decreased as the cultures aged (7-day culture, 71%; 14-day
      culture, 5%; 21-day culture, 0%). In conclusion, our results show a strong
      association between the intensity of the neutrophil chemoattractant activity and
      TNF concentration in the supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8547852
TI  - Clastogenic effect of cisplatin on Wistar rat bone marrow cells.
AB  - The clastogenic effect of the drug cis-diamminedichloroplatinum II (cisplatin,
      CDDP) was investigated in Wistar rat bone marrow cells. Male rats, 3 per
      treatment time, aged 4 months and weighing 250-350 g were injected
      intraperitoneally with 6.0 mg/kg CDDP solution, and the control group received
      isotonic saline. The animals were sacrificed 6, 12, 18, 24 and 48 h after the
      injection. The chromosome preparation was obtained from bone marrow cells.
      Chromatid and chromosome aberrations were investigated in 300 metaphases per
      animal. A significant increase in number of chromosome aberrations was observed
      from 6 to 24 h, the majority being of the break and gap type. After 48 h a
      progressive reduction was observed, without differences from the negative
      control. These data confirm the mutagenic effect of CDDP in rats demonstrated for
      mice bone marrow by micronuclei assay, for murine ovary cells and mice
      spermatocytes.

PMID- 8547853
TI  - Chemical and biological demonstration of the presence of monofluoroacetate in the
      leaves of Palicourea marcgravii St. Hil.
AB  - Cattle losses in Brazil have been attributed to Palicourea marcgravii St. Hil., a
      toxic plant for cattle. The crude extract from the leaves of P. marcgravii was
      successively fractionated using solvents with different polarities to determine
      whether monofluoroacetic acid and/or some other substance present in the leaves
      may be responsible for the acute symptoms caused by the plant. Authentic sodium
      monofluoroacetate (SMFA) was used for comparison. The only P. marcgravii fraction
      which induced seizures and death in intoxicated rats was water soluble. The signs
      and symptoms induced in the animals by the crude extract and water-soluble
      fraction were the same as induced by SMFA and included tonic seizures and other
      actions on the CNS. The dose-lethality and dose-latency to the 1st seizure curves
      constructed for the water-soluble fraction of the leaf extract (30-100 mg/kg) and
      SMFA (0.6-3.0 mg/kg) were parallel. Five animals per dose were used. The potency
      ratio of SMFA in relation to the water-soluble fraction of the leaf extract was
      53.8 (dose-lethality curve) and 64.1 (dose-latency to the 1st seizure curve). The
      water-soluble fraction contained a substance with hRf = 20 which was the same as
      that of authentic SMFA. The 19F NMR spectra of authentic SMFA and the P.
      marcgravii water-soluble fraction were identical. These data demonstrate the
      presence of SMFA in the water-soluble fraction of P. marcgravii leaves and show
      that monofluoroacetate is the active principle responsible for the signs and
      symptoms of acute intoxication.

PMID- 8547854
TI  - The diameter of water pores formed by colicin Ia in planar lipid bilayers.
AB  - The effective size of colicin Ia channel was tested by a recently described
      method (FEMS, Microbiology and Immunology (1992). 105: 93-100) in which the
      nonelectrolyte molecules with different hydrodynamic diameters (0.52 to 5.0 nm)
      were used as molecular tools. We have shown that despite low conductance (55-105
      pS at 1.5 M KCl, pH 7.0) the ion channels formed by colicin Ia have a fairly
      large water pore diameter equal to 1.66-1.88 nm. The results are discussed in
      terms of an energetic barrier for ions passing into the channel lumen.

PMID- 8547855
TI  - Glycine blocks the pressor response to L-glutamate microinjected into the nucleus
      tractus solitarii of conscious rats.
AB  - Microinjection of L-glutamate into the nucleus tractus solitarii (NTS) of
      conscious freely moving Wistar rats (240-260 g) produces pressor (+48 +/- 4 mmHg)
      and bradycardic (-153 +/- 20 bpm) responses. In the present study L-glutamate
      (2.5 nmol/100 nl) was microinjected before and after microinjection of increasing
      doses of glycine (10, 25 and 50 nmol/100 nl, N = 6) or saline (vehicle/100 nl, N
      = 6) into the NTS. Microinjections of increasing doses of glycine into the NTS
      produced a dose-dependent reduction in the pressor but not in the bradycardic
      responses to L-glutamate. [10 nmol (+29 +/- 5 mmHg and -110 +/- 18 bpm), 25 nmol
      (+12 +/- 7 mmHg and -88 +/- 21 bpm) and 50 nmol (+4 +/- 2 mmHg and -100 +/- 31
      bpm)] The dose-dependent blockade of the pressor response to L-glutamate by
      glycine suggests an inhibitory neuromodulatory role for this amino acid in the
      sympatho-excitatory activity produced by L-glutamate microinjection into the NTS.

PMID- 8547856
TI  - Effects of caffeine and tryptophan on rectal temperature, metabolism, total
      exercise time, rate of perceived exertion and heart rate.
AB  - Stimulant properties during exercise have been attributed to caffeine (CAF) and
      tryptophan (Trp). The purpose of the present study was to investigate the effects
      of CAF and Trp ingestion on rectal temperature (Tre), total exercise time (TET),
      oxygen consumption (VO2), carbon dioxide production (VCO2), pulmonary ventilation
      (VE), heart rate (HR) and rate of perceived exertion (RPE) during exercise on a
      cycle ergometer at 80% of maximal work load, in eight healthy male volunteers.
      Each subject abstained from caffeine for 48 h and from animal-derived foods for
      36 h before each experiment. Aerobic capacity was determined on the first day. In
      consecutive trials, conducted in a double-blind, randomized, crossed-over manner,
      each subject received capsules containing CAF (10 mg/kg), Trp (1.2 g), a
      combination of the two (CAF+Trp), and lactose (PLA), 1 h before exercise. Plasma
      CAF concentration (PC) was measured by high performance liquid chromatography
      (HPLC), before (basal concentration) and 1 and 2 h after ingestion of the
      capsules. At both times after CAF or CAF+Trp ingestion, the PC was elevated
      compared with the basal concentration (P < 0.05). During exercise, significant
      increases occurred with time in Tre, TET, VO2, VCO2, VE, HR and RPE (P < 0.01)
      while no significant difference was observed when CAF or CAF+Trp were compared
      with control values. Under the conditions of this study, CAF and/or Trp did not
      affect the physiological parameters measured before, during or after exercise at
      80% of maximal work load.

PMID- 8547857
TI  - SDZ 216-525, a selective 5-HT1A receptor antagonist, reverts zinc-induced
      inhibition of water intake in dehydrated rats.
AB  - Zinc is found in many brain regions where it participates in important processes
      such as neurotransmission and neuromodulation. We previously demonstrated that
      acute third ventricle injection of zinc inhibits water intake in dehydrated rats.
      The present study was undertaken to explore a possible link between zinc-induced
      inhibition of water intake in dehydrated rats and serotonergic systems in the
      brain. Adult, male Wistar rats had the third ventricle cannulated a week before
      the experiments. After an overnight period of water deprivation, the animals (N =
      12 per group) received acute intracerebroventricular injections (2 microliters)
      of Zn(Ac)2 (6.7, 67.1 and 671.6 ng/rat). Control animals (N = 12) received NaAc
      (671.6 ng/rat). Zinc-treated animals displayed a significant, dose-dependent
      reduction in water intake. Water intake after 120 min was 7.70 +/- 0.50 ml in
      control (NaAc-treated) dehydrated rats while animals treated with the highest
      dose of Zn(Ac)2 drank 2.63 +/- 0.73 ml. Third ventricle injections of SDZ 216
      525, a selective 5-HT1A receptor antagonist, 45 min before zinc administration,
      generated a dose-dependent reversal of zinc-induced thirst blockade in water
      deprived rats. At the highest dose used (10 micrograms/rat), the water intake of
      the animals after 120 min was 7.30 +/- 0.23 ml, a value equal to that of control
      animals. These data suggest that zinc may decrease water intake in dehydrated
      rats by activation of a 5-HT1A receptor-related mechanism.

PMID- 8547858
TI  - Acute effect of thyroxine on pituitary neuromedin B content of hypothyroid rats
      and its correlation with TSH secretion.
AB  - Neuromedin B (NB) is a bombesin-like peptide that has been recently characterized
      as a physiological paracrine/autocrine inhibitor of thyrotropin (TSH) secretion.
      We report here the time course of the effect of thyroxine (T4) administration to
      hypothyroid rats on the anterior pituitary content of NB. Dutch-Miranda male rats
      weighing 250-300 g received 0.03% methimazole in the drinking water for 3 weeks.
      T4 (0.8 microgram/100 g body weight, sc) was given 1/2, 1, 3 or 6 h before
      sacrifice. One group received saline rather than T4 (hypothyroid control). The
      groups contained 6 to 8 animals each. NB, extracted from tissue by boiling in
      acetic acid, was measured by radioimmunoassay, using a highly specific antiserum.
      Pituitary NB content was significantly increased 4-fold, as early as 1/2 h after
      T4 injection, while serum TSH level was similar to that of the hypothyroid
      control group. The peak response to T4 was at 3 h after injection, when NB
      content was increased 8-fold (hypothyroid: 45 +/- 8; 1/2 h, 223 +/- 15; 1 h, 203
      +/- 48; 3 h, 383 +/- 31; 6 h, 224 +/- 30 fmol/mg protein) and serum TSH decreased
      to the level of normal rats (0.93-1.5 ng/ml) generally observed in our laboratory
      (hypothyroid: 31 +/- 3; 1/2 h, 26 +/- 3; 1 h, 31 +/- 2; 3 h, 1.3 +/- 0.1; 6 h,
      3.7 +/- 0.6 ng/ml). These data suggest that NB synthesis is rapidly induced by
      thyroxine and this might represent a new regulatory path involved in the acute
      inhibitory effect of thyroid hormones on TSH secretion.

PMID- 8547859
TI  - Psychosocial morbidity in bone marrow transplant recipients: a prospective study.
AB  - Previous work has demonstrated that psychosocial morbidity may occur following
      bone marrow transplantation (BMT), but few prospective quantitative data are
      available, especially in adults. We have conducted a prospective psychological
      assessment of 36 patients accepted onto our BMT programme, of whom 31 proceeded
      to transplant. Patients were assessed shortly before admission for BMT and again
      at about 4 and 8 months after the procedure, using the following tools: Hospital
      Anxiety and Depression Scale (HAD), Social Adjustment Scale-Self Report and the
      Present State Examination (PSE). A 54% incidence of psychosocial morbidity (as
      assessed by either an abnormal HAD or PSE result) was found among those cases
      assessed both before and at least once after BMT. Significant psychosocial
      morbidity was still present 6-9 months following BMT. Cases scoring abnormally
      following BMT in general also scored abnormally before transplant, suggesting a
      predictive value of pre-BMT psychological assessment. Psychological morbidity was
      unrelated to the type of transplant. Patients with chronic myeloid leukaemia had
      a higher incidence of post-BMT psychosocial morbidity than patients with other
      diagnoses; it is suggested that this may be due to their lack of previous
      experience of intensive haematological therapy. Psychological evaluation may help
      in identifying patients at risk of post-BMT psychosocial problems.

PMID- 8547860
TI  - Histoincompatibilities in ABDR-matched unrelated donor recipient combinations.
AB  - To get an insight into the degree of major histocompatibility mismatches in
      donor/recipient (D/R) combinations who were 'ABDR-matched' by serology for class
      I and by oligotyping for DR1-14 (low resolution typing), we performed additional
      HLA testing using a combination of molecular, biochemical and cellular
      techniques. For class II we used extended oligotyping, discriminating all the
      common DRB1/B3/B5-subtypes. For class I (-subtypes) we used oligotyping (HLA-A2,
      A3,-B35,-B41,-B44), sequencing (HLA-B35,-B41,-Cw16), isoelectrofocusing (IEF),
      primary cytotoxic T lymphocyte (CTL) assays and class I-subtype specific T cell
      clones. In addition, all combinations were serologically typed for HLA-C. This
      high resolution typing by the combination of techniques revealed numerous
      histoincompatibilities. Fifty-three per cent of all 'ABDR-matched' combinations
      tested (n = 198) appeared to be DR incompatible. Moreover, independent of the
      presence of a class II mismatch, 47% of the donors tested (n = 131) displayed
      pretransplant cytotoxic activity against the patient. This activity was found to
      be rigorously correlated with the presence of class I incompatibilities,
      predominantly HLA-A,-B subtypes and HLA-C. Thus, although the D/R pairs had been
      originally matched for AB including serological splits and by generic class II
      typing, only 28% of the pairs were in fact ABCDR identical. As many as 38% of the
      D/R pairs were mismatched for one, 14% for two, 13% for three and 6% for four A,
      B, C or DRB1 antigens. We conclude that the presence of such a high number of
      histoincompatibilities in a group of relatively well matched D/R pairs will
      severely hinder the analysis of the role of HLA in marrow transplantation and
      that conclusions from studies in which D/R pairs are matched by conventional
      typing must be interpreted with extreme caution.

PMID- 8547861
TI  - Allogeneic transplantation with blood stem cells mobilized by rhG-CSF for
      hematological malignancies.
AB  - Allogeneic blood stem cell (BSC) transplantation has been performed
      experimentally in some patients with success. Wider application of this
      therapeutic modality has been hampered ultimately by many factors, mainly the
      concern that infusion of large numbers of donor T cells could result in an
      increased incidence and severity of graft-versus-host disease (GVHD). We report
      the short-term results of 17 allogeneic BSC transplants in patients with
      hematologic malignancies. When compared to standard BMT results, BSC transplants
      showed the advantages of faster engraftment, shorter hospital stay and fewer
      antibiotic needs. The incidence and severity of GVHD, as well as the general BMT
      associated morbidity, was comparable between the two groups. BSC collection by
      apheresis was well tolerated and associated with less morbidity for donors,
      probably reducing the cost of the treatment. The collection of BSC was a single
      apheresis procedure and yielded adequate numbers of stem cells to ensure
      engraftment. Although this was not a prospective randomized study, the data
      obtained are encouraging and warrant more prospective and controlled studies.

PMID- 8547862
TI  - A phase I trial of interleukin 3 (IL-3) pre-bone marrow harvest with granulocyte
      macrophage colony-stimulating factor (GM-CSF) post-stem cell infusion in patients
      with solid tumors receiving high-dose combination chemotherapy.
AB  - In humans, interleukin 3 (IL-3) administration increases the cellularity and
      cycling of bone marrow progenitor cell populations. Initially, in primates and
      then in humans, IL-3 in sequence with GM-CSF has been shown to stimulate
      multilineage hematopoiesis. Based upon these effects, we designed a phase I trial
      of daily IL-3 administered subcutaneously for 10 days at dose levels of 2.5, 5.0,
      10.0, 12.5, and 15.0 micrograms/kg followed within 72 h by bone marrow harvest,
      high-dose chemotherapy, and following chemotherapy, a fixed dose (5.0
      micrograms/kg/day) of GM-CSF and bone marrow rescue. The study was designed to
      assess the toxicity and biological effects of IL-3 administered alone prior to
      bone marrow harvest and to determine the safety and clinical effects of IL-3
      stimulated bone marrow with GM-CSF following high-dose combination chemotherapy.
      A total of 19 patients with chemotherapy-sensitive non-hematologic malignancies
      (13 breast, five ovarian, and one testicular cancer) were enrolled. IL-3 up to
      15.0 micrograms/kg/day could be administered without dose-limiting toxicities.
      Flu-like symptoms and headaches were common and poorly tolerated at the highest
      IL-3 dose. Significant increases in neutrophil counts (P = 0.018) were observed
      following IL-3. Overall, IL-3 administration was associated with a modest, but
      significant increase in CFU-GM within the bone marrow (P = 0.034). IL-3
      administration had no consistent effect on CD34+ cell number within bone marrow.
      For the entire group, engraftment of neutrophils to greater than 0.5 x 10(9)/l
      occurred at a median of 21 days (range of 13-63 days) and platelet independence
      occurred at a median of 17 days (range 11-120 days). When IL-3 dose levels were
      analyzed separately, engraftment of neutrophils and platelets, blood product
      (platelets and packed RBCs) utilization, and discharge date were not superior in
      those treated with the higher dose (15.0 micrograms/kg) of IL-3. While higher
      doses of IL-3 were associated with more toxicity, they did not appear to enhance
      the stem cell pool or speed engraftment later. The effects of pre-bone marrow
      harvest IL-3 are modest and likely not as impressive as other approaches aimed at
      enhancing hematologic recovery following high-dose chemotherapy.

PMID- 8547863
TI  - Bone marrow transplantation for Philadelphia-chromosome-positive acute
      lymphoblastic leukemia.
AB  - The outcome of 14 bone marrow transplants (BMT) (autologous 4; allogeneic 10) for
      Philadelphia-chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) was
      analyzed. Preparative regimens consisted of etoposide (VP16) (30 or 45 mg/kg BW)
      (n = 14), cyclophosphamide (CY)(120 mg/kg BW) (n = 14), and total body
      irradiation (TBI)(12 Gy) (n = 13) or busulfan (Bu)(16 mg/kg) (n = 1). All
      patients receiving autologous marrow were in complete remission (CR) (three
      patients in 1.CR, one patient in 2.CR) at the time of BMT. For allogeneic BMT
      (nine related, one unrelated donor), seven patients were in first CR, two
      patients in first refractory relapse, and one patient in second relapse. With a
      median follow-up of 503 days (range 93-1522 days), eight out of 14 patients are
      alive in remission (six out of 10 patients receiving allogeneic, and two out of
      four patients receiving autologous BMT). Disease-free survival for all patients
      is 46%. Causes of death were relapse (n = 3) and transplant-related toxicity (n =
      3). All patients tested for the bcr/abl rearrangement by reverse transcriptase
      polymerase chain reaction (RT-PCR) were negative 4 weeks post-BMT. Two of the
      three patients who subsequently relapsed were repeatedly RT-PCR positive prior to
      relapse (test not done in the third). Considering the negligible cure rate of Ph1
      positive ALL with conventional chemotherapy regimens, our data support the
      concept of early (> or = 1 CR) BMT (allogeneic > autologous (purged) following
      triple therapy with TBI, VP16, and CY.

PMID- 8547864
TI  - Fatal pneumopathy in children after bone marrow transplantation--report from the
      Italian Registry. Italian Association of Pediatric Hematology-Oncology BMT Group.
AB  - We have examined data reported in the AIEOP-BMT Registry in order to determine
      the incidence, causes and risk factors for fatal pneumopathy after bone marrow
      transplantation in a pediatric population. Overall, in the Registry 1134 children
      are reported, 531 of whom received an autologous BMT, 468 allomatched BMT, eight
      syngeneic, 75 mismatched, 29 unrelated and 23 peripheral blood progenitor cells
      as rescue after myeloablative therapy in the period 1983-1993. 198 patients out
      of 1134 (17%) died of transplant-related causes and 86 of them died of pulmonary
      complications: 12 were recorded as fungal pneumonia, eight bacterial, four
      bacterial and fungal, six viral, two Pneumocystis carinii pneumonia, 12 ARDS, 13
      interstitial, 29 unspecified 'respiratory failure'. Multivariate analysis showed
      that only type of graft and presence or absence of Pneumocystis carinii
      prophylaxis influence the cumulative incidence of fatal pneumonia. After
      autologous BMTs only Pneumocystis carinii prophylaxis was significant in
      multivariate analysis. After allogeneic BMTs multivariate analysis showed that
      BMT type, Pneumocystis carinii prophylaxis and GVHD grade seem to maintain their
      influence on cumulative incidence of fatal pneumonia. After BMT the incidence of
      fatal pneumopathy in children is low (9%), but it represents the second cause of
      death after primary disease. Pneumocysti carinii prophylaxis should also be given
      after autologous BMT.

PMID- 8547865
TI  - Autopsy-identified infections among bone marrow transplant recipients: a clinico
      pathologic study of 56 patients. Bone Marrow Transplantation Team.
AB  - We reviewed the autopsy records of 56 patients who had undergone BMT at the
      Detroit Medical Center during 1988-1992. Most patients (43 of 56) had died within
      2 months of BMT. One or more infections were identified at autopsy in 25 of 40
      (63%) allogeneic and four of 16 (25%) autologous BMT recipients. Microorganisms
      isolated at autopsy were cytomegalovirus (CMV) (14 patients), yeasts (13
      patients), molds (aspergillus six patients, mucor one patient) and bacteria
      (seven patients). Presence of infection was not identified or proven prior to
      death in nine of 14 patients (65%) with CMV, six of 13 patients (46%) with yeasts
      and four of six patients (67%) with aspergillus. Most bacterial infections (five
      of seven patients) were identified ante-mortem. Lungs and the gastrointestinal
      tract were the organ systems mostly involved in patients with or without autopsy
      identified infections. Pathologic findings in the lungs were diffuse alveolar
      damage, interstitial pneumonia and bronchopneumonia and, in the gastrointestinal
      tract, were ulcerations and hemorrhages of esophagus, stomach, small and large
      intestines. Examination of the heart showed non-bacterial thrombotic endocarditis
      (NBTE) in five patients, four with right-sided involvement only. Failure to
      identify non-bacterial pathogens ante-mortem and their frequent association with
      mortality in bone marrow transplant patients are high-lighted in the present
      study.

PMID- 8547866
TI  - Joint influence of natural killers (NK) and hemopoietic stroma on rejection of
      parent stem cells.
AB  - The growth of hemopoietic stem cells of C57BL/6 mice was explored in syngeneic
      and semi-syngeneic foci of heterotopic hemopoiesis, formed under the kidney
      capsule of (CBA x C57BL/6)F1 recipients with and without prior treatment with
      cyclophosphamide or fractionated irradiation, which is known to abrogate hybrid
      resistance and NK cell activity. Our results show that the suppression of the
      growth of parent stem cells in semi-syngeneic F1-recipients is due to NK cell
      participation. However, no inhibition was found in the growth of identical cells
      in the foci of syngeneic hemopoietic stroma in the same recipients, despite the
      presence of NK cell activity. The experimental model used shows clearly that
      hybrid resistance is the result of the joint involvement of NK cells and the semi
      syngeneic stroma.

PMID- 8547867
TI  - Description of an efficient and highly informative method for the evaluation of
      hematopoietic chimerism following allogeneic bone marrow transplantation.
AB  - The significance of full donor hematopoietic engraftment or hematopoietic
      chimerism (HC) following allogeneic bone marrow transplantation (BMT) remains
      unresolved. To study this phenomenon properly, informative genetic loci must be
      prospectively identified and followed for several years after allogeneic BMT in
      large numbers of consecutive patients treated with uniform conditioning and
      immunosuppressive regimens. In addition, sensitive methods that can be performed
      on small numbers of cells are required in order to extend the analysis for HC to
      individual hematopoietic lineages and specific anatomic compartments (eg bone
      marrow, peripheral blood, and lymph nodes). Although polymerase chain reaction
      (PCR) amplification of polymorphic minisatellite and microsatellite DNA loci has
      improved the sensitivity of detection of HC, a single rapid, sensitive, and
      highly informative test that can consistently distinguish donor from recipient
      elements for the majority of allogenic BMT patients has not been described. In
      the present report, we describe a single PCR that simultaneously amplifies four
      microsatellites and was able to identify an informative locus in 48 of 50 (96%)
      consecutive recipient/donor pairs. A HC of as little as 0.5% could be detected,
      and HC of 10% could be detected in as few as 100 cells. This technique should
      allow the detection of an informative microsatellite locus in most patients
      undergoing allogeneic BMT, using minimal amounts of DNA and requiring 16 h for
      completion.

PMID- 8547868
TI  - Outpatient bone marrow harvest: the Cleveland Clinic experience.
AB  - Patients undergoing a bone marrow harvest have traditionally been hospitalized
      for several days. Recently, the feasibility of outpatient bone marrow harvesting
      has been reported. We retrospectively examined the results of 485 patients
      undergoing an outpatient bone marrow harvest from 1989 to 1993. One hundred and
      eleven patients were normal donors and the remaining patients were undergoing a
      bone marrow harvest for autologous transplants. Four hundred and eighty one
      patients (99%) were discharged within 12 h of the harvest and none have developed
      long-term complications from the procedure. We additionally analyzed harvest
      yield with respect to time under anesthesia and underlying diagnosis.
      Surprisingly, time under anesthesia correlated negatively with harvest yield (P =
      0.0001). After adjusting for volume harvested and time under anesthesia, harvest
      yield was higher in normal donors and patients with breast cancer than for
      patients with non-Hodgkin's lymphoma and Hodgkin's disease. We conclude that
      outpatient harvesting is safe. The negative correlation of time under anesthesia
      with harvest yield may be a result of variables which are difficult to quantify,
      such as bone marrow microenvironment.

PMID- 8547869
TI  - Comparison of Cobe Spectra and Haemonetics MCS-3P cell separators for peripheral
      blood stem cell harvesting.
AB  - A prospective study was undertaken to compare the total nucleated cell (TNC),
      mononuclear cell (MNC), CD34+ cell, and CFU-GM yields of two different cell
      separators. A Haemonetics MCS-3P and a Cobe Spectra machine were used to
      leukapherese 10 patients with malignant diseases on 4 consecutive days after
      mobilization with G-CSF. All patients were harvested twice on each machine for a
      fixed period of time. The blood volume processed (10.47 vs 3.79 l, P < 0.001),
      MNC yield (2.66 vs 0.90 x 10(8)/kg; P < 0.001), MNC yield rate (1.66 vs 0.55 x
      10(6)/kg/min; P < 0.001), MNC purity (81 vs 42%; P < 0.001), CFU-GM yield (18.1
      vs 5.5 x 10(4)/kg; P = 0.001), and CFU-GM yield rate (11.27 vs 3.42 x
      10(2)/kg/min; P = 0.001) were significantly higher with the Spectra. The CD34+
      cell yields and yield rates were comparable. Although CFU-GM and MNC yields per
      unit blood volume processed were comparable for both machines, there was a trend
      for higher CD34+ yields per unit volume processed with MCS-3P. We conclude that
      Spectra is faster than MCS-3P with more blood processed per unit time resulting
      in higher cell yields, but yields per unit volume processed are comparable for
      both machines. The choice of machine for a given patient depends upon
      convenience, venous access and the time available.

PMID- 8547870
TI  - Successful treatment of parvovirus B19 infection and red cell aplasia occurring
      after an allogeneic bone marrow transplant.
AB  - Chronic parvovirus B19 infection in the immunocompromised host may cause severe
      anaemia secondary to failure of erythropoiesis. This has been previously
      documented in patients with the Acquired Immune Deficiency Syndrome (AIDS),
      congenital immunodeficiencies and in children with acute lymphoblastic leukaemia
      during maintenance chemotherapy. We describe persistent parvovirus infection in a
      14-year-old boy after HLA-matched sibling allogeneic bone marrow transplantation
      for acute lymphoblastic leukaemia in second remission.

PMID- 8547871
TI  - Thrombotic thrombocytopenic purpura associated with FK506 following bone marrow
      transplantation.
AB  - Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
      have been observed after bone marrow transplantation (BMT), typically occurring 1
      6 months following BMT. We describe two patients who developed TTP very early
      after BMT while receiving intravenous FK506. They were treated with platelet
      support and plasma exchange (PE) using either fresh frozen plasma (FFP) or
      cryosupernatant fraction of plasma (CFP), resulting in remission of TTP activity.

PMID- 8547872
TI  - Shwachman-Diamond syndrome and matched unrelated donor BMT.
AB  - A 5 year old with Shwachman-Diamond syndrome (SDS) developed acute monoblastic
      leukaemia following a period of myelodysplasia associated with a clonal
      cytogenetic abnormality involving chromosome 7. Matched unrelated BMT was carried
      out using standard CY/TBI conditioning and GVHD prophylaxis protocols. The
      patient experienced no toxicity, had temporary committed progenitor cell
      engraftment but eventually died from bone marrow failure 1 year post-transplant.
      This report, to our knowledge, documents the first reported case of matched
      unrelated donor BMT for SDS/AML and we speculate that standard conditioning
      regimens are probably safe in this group of patients.

PMID- 8547873
TI  - Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an
      HLA-identical unrelated donor.
AB  - We describe the case of a 41-year-old female who underwent allogeneic blood cell
      transplantation with CD34(+)-enriched cells from an HLA-matched unrelated donor
      for AML in second CR. The conditioning regimen consisted of TBI (12 Gy), VP16
      (1800 mg), cyclophosphamide (7200 mg), and ATG (7200 mg). GVHD prophylaxis
      consisted of CsA and a short course of MTX. Receiving G-CSF from day +1,
      engraftment occurred on day +19 after stem cell infusion. Starting on day +10,
      GVHD grade II (skin and liver) developed that responded to high-dose steroid
      therapy. The patient died on day +38 due to suspected cerebral aspergillus
      infection. This case demonstrates the feasibility of primary transplantation of
      CD34(+)-enriched allogeneic peripheral stem cells from a matched unrelated donor
      leading to engraftment of donor cells.

PMID- 8547874
TI  - Multiple granulocyte transfusions facilitating successful unrelated bone marrow
      transplantation in a patient with very severe aplastic anemia complicated by
      suspected fungal infection.
AB  - The successful use of granulocyte transfusions in a patient undergoing volunteer
      unrelated donor BMT for very severe aplastic anemia complicated by presumed
      fungal infection is described. Granulocytes were obtained by leukapheresis of
      normal volunteer donors stimulated by granulocyte colony-stimulating factor. The
      yields of granulocytes obtained by this method were sufficient to produce
      sustained neutrophil increments in the recipient throughout the transplant
      course. In vitro studies indicated that granulocytes were functionally normal, a
      finding which was supported clinically by the rapid resolution of infection, even
      in the setting of immunosuppression post-transplantation. This demonstrated the
      potential value of granulocyte transfusions in high-risk BMT.

PMID- 8547875
TI  - Recombinant tissue plasminogen activator (rTPA) for hepatic veno-occlusive
      disease after allogeneic BMT in a pediatric patient.

PMID- 8547876
TI  - Predicting tumor recurrence in autologous transplantation.

PMID- 8547877
TI  - Methotrexate and delayed engraftment in allogeneic bone marrow transplantation.

PMID- 8547879
TI  - Marrow transplantation via e-mail.

PMID- 8547878
TI  - Pregnancy after TBI.

PMID- 8547880
TI  - Iodine-123-labeled glucose analogs: prospects for a single-photon-emitting analog
      of fluorine-18-labeled deoxyglucose.

PMID- 8547881
TI  - Planar myocardial imaging in the baboon model with iodine-123-15
      (iodophenyl)pentadecanoic acid (IPPA) and iodine-123-15-(P-iodophenyl)-3-R,S
      methylpentadecanoic acid (BMIPP), using time-activity curves for evaluation of
      metabolism.
AB  - The purpose of this study was to compare by planar myocardial scintigraphy the
      kinetics of iodine-123-15-(iodophenyl)pentadecanoic acid (123I-pPPA and 123I
      oPPA), and of iodine-123-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid (BMIPP),
      firstly in normal baboons, and subsequently after blocking fatty acid oxidation
      by a carnitine palmitoyl transferase I(CPT1) inhibitor. The induced changes in
      myocardial metabolism were reflected in the dynamic behaviour of the three
      tracers. pPPA and oPPA to a large extent, provided information on beta-oxidation
      changes in the myocardium: beta-oxidation participation changed from 47% and 50%,
      respectively to 17% and 23% after inhibition. BMIPP provided better images and
      reflected largely on changed tracer incorporation into the neutral lipid pools.
      The beta-oxidation contributed only about 10% towards the metabolic pathway of
      BMIPP. The information obtained in this study could help determine the tracer of
      choice for SPECT, whereby myocardial viability could optimally be revealed.

PMID- 8547882
TI  - Transition metal chemistry of main group hydrazides, Part 14: Evaluation of new
      Tc-99m chelates of thiol functionalized phosphorus hydrazides.
AB  - Ligands containing a combination of amine or amide nitrogens and thiol
      functionalities have been found to form stable chelates with Tc-99m, presumably
      in oxidation state +5. Two new thio-phosphorus monohydrazides
      [(MeO)2P(S)NMeNHCH2C6H4SH], SL1 and [(MeO)2P(S)NMeNHC(O)C6H4SH], SL2 were
      synthesized and their complexation properties with Re(V) and Tc-99m have been
      studied. Neutral-lipophilic Tc-99m chelates with both SL1 and SL2 were formed in
      high yields (95-97%) as a single species ascertained by electrophoresis and
      reversed-phase HPLC. Biodistribution studies show good in vivo stability and
      primary clearance of both 99mTc chelates is via the hepatobiliary pathway. Re(V)
      complexes with SL1 and SL2 were also synthesized using the ReOCl3(PPh3)2
      precursor to obtain the product ReOCl(L)(PPh3), where L = SL1 or SL2. H+ was lost
      from the N-atom and the thiol group in these Re chelates. Even though the Tc-99m
      chelates of SL1 and SL2 formed at tracer levels are not identical to the Re
      chelates (different synthons were used), the Re data suggests complexation of Tc
      99m by these hydrazido-thiol ligands will be similar to N,S ligand systems
      previously used. The good in vitro and in vivo stability and high yields of the
      Tc-99m complexes of SL1 and SL2 indicate the potential hydrazido-thiols hold for
      use as a basis in formulating new Tc-99m radiopharmaceuticals, particularly when
      thiol moieties are used in conjunction with multi-functional phosphorous
      hydrazide compounds.

PMID- 8547883
TI  - New hydroxybenzyl and hydroxypyridylmethyl substituted triazacyclononane ligands
      for use with gallium(III) and indium(III).
AB  - The 67Ga(III) and/or 111In(III) complexes of four new hexadentate ligands have
      been prepared and evaluated in vitro and in vivo. These substituted
      triazacyclononane ligands bind the metal ion through three tertiary ring
      nitrogens and three oxygens from pendant phenolic or hydroxypyridyl arms. The
      hydroxypyridyl moieties increase the aqueous solubility of the metal complexes
      while retaining a lipophilic character. As indicated by their large positive
      partition coefficients, the phenolic ligands proved to be significantly more
      lipophilic than the hydroxypyridyl ligands. Biodistribution in Sprague-Dawley
      rats indicated that the more lipophilic phenolic complexes cleared the body
      primarily through the liver, while the less lipophilic hydroxypyridyl complexes
      cleared rapidly, primarily through the kidney. To differentiate the clearance
      characteristics of these radiolabeled compounds, radiochemical purity of selected
      complexes in vivo was measured. The complexes were evaluated for overall charge
      in vitro and in vivo, in plasma samples. In addition, plasma and urine were
      analyzed for possible metabolites. With one exception, each complex was
      unmetabolized in vivo. All complexes and metabolites formed were neutral in vitro
      and in vivo. Extended stability in serum of selected radiometal complexes has
      been measured. Each complex measured was stable to exchange with transferrin, up
      to 72 h, as expected from the large stability constants of the complexes. The
      clearance characteristics of the hydroxypyridyl and phenolic ligands, however,
      were markedly different. The rapid hepatic clearance of the phenolic ligands
      indicates potential as bifunctional chelates for Ga(III) or In(III).

PMID- 8547884
TI  - Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody
      in severe combined immunodeficiency mice.
AB  - Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is
      overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To
      examine the potency of anti-Tac for targeting of ATL, biodistributions of
      intravenously administered 125I- and 111In-labeled anti-Tac were examined in
      severe combined immunodeficiency (SCID) mice inoculated with ATL cells.
      Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus.
      The trafficking of ATL cells in SCID mice was detected using 111In-oxine-labeled
      ATL cells. These results were coincident with the histologically confirmed
      infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting
      of ATL.

PMID- 8547885
TI  - Experimental models, protocols, and reference values for evaluation of iodinated
      analogues of glucose.
AB  - For an iodinated analogue of glucose to be useful for evaluating glucose uptake
      using single-photon emission computed tomography (SPECT), it must enter the cell
      via the same transporter as glucose and accumulate within the cell without being
      degraded. The biological behavior of the iodinated tracer must therefore be
      similar to that of 2-deoxy-D(-)[1-14C]-glucose (2-DG). In the present study, four
      experimental models (biodistribution in mouse, isolated rat heart, human
      erythrocytes in suspension and cultured neonatal rat cardiomyocytes) have been
      chosen and protocols have been set up which allow for the examination of small
      quantities of iodinated analogues of glucose. The uptakes of 2-DG and of L(-)[1
      14C]-glucose have been measured in these models to establish reference values
      which will be compared with uptake values for iodinated analogues of glucose.

PMID- 8547886
TI  - An improved 191Os/191mIr generator using a hybrid anion exchanger.
AB  - Iridium-191m is an attractive radionuclide for first-pass radionuclide
      angiography, but development of an 191Os/191mIr generator with high 191mIr yield
      has proven difficult. The use of trans-dioxobisoxalatoosmate(VI) as a parent
      species results in a higher initial yield (20 to 25%/mL), but the yield decreases
      over time. Using an anion-exchange column of tridodecylmethylammonium chloride
      treated silica gel and AG MP-1 resin, we have developed an improved 191Os/191mIr
      generator with higher initial yield (25 to 30%/mL) and a slower rate of decrease
      than the previous design.

PMID- 8547887
TI  - Plasma input function determination for PET using a commercial laboratory robot.
AB  - A commercial laboratory robot system (Zymate PyTechnology II Laboratory
      Automation System) was interfaced to standard and custom laboratory equipment and
      programmed to perform rapid radiochemical assays necessary for plasma input
      function determination in quantitative PET studies in humans and baboons. A
      Zymark XP robot arm was used to carry out two assays: (1) the determination of
      total plasma radioactivity concentrations in a series of small-volume whole blood
      samples and (2) the determination of unchanged (parent) radiotracer in plasma
      using only solid phase extraction methods. Steady state robotic throughput for
      determination of total plasma radioactivity in whole blood samples (0.350 mL) is
      14.3 samples/h, which includes automated centrifugation, pipetting, weighing and
      radioactivity counting. Robotic throughput for the assay of parent radiotracer in
      plasma is 4-6 samples/h depending on the radiotracer. Percents of total
      radioactivities present as parent radiotracers at 60 min, postinjection of 25 +/-
      5.0 (N = 25), 26 +/- 6.8 (N = 68), 13 +/- 4.4 (N = 30), 32 +/- 7.2 (N = 18), 16
      +/- 4.9 (N = 20), were obtained for carbon-11 labeled benztropine, raclopride,
      methylphenidate, SR 46349B (trans, 4-[(3Z)3-(2-dimethylamino-ethyl) oxyimino-3 (2
      fluorophenyl)propen-1-yl]phenol), and cocaine respectively in baboon plasma and
      84 +/- 6.4 (N = 9), 18 +/- 11 (N = 10), 74 +/- 5.7 (N = 118) and 16 +/- 3.7 (N =
      18) for carbon-11 labeled benztropine, deprenyl, raclopride, and methylphenidate
      respectively in human plasma. The automated system has been used for more than 4
      years for all plasma analyses for 7 different C-11 labeled compounds used
      routinely in our laboratory. The robotic radiotracer assay runs unattended and
      includes automated cleanup procedures that eliminates all human contact with
      plasma-contaminated containers.

PMID- 8547889
TI  - Synthesis and organ distribution of [18F]fluoro-Org 6141 in the rat: a potential
      glucocorticoid receptor ligand for positron emission tomography.
AB  - For the synthesis of [18F]Fluoro-Org 6141 via a nucleophilic substitution
      reaction with 18F-, the tosyl group was chosen as the leaving group because of
      its stability and excellent leaving group ability. The biodistribution of the
      high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand
      [18F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was
      examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar
      rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85
      MBq of [18F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18F
      activity uptake were monitored for 3 h using a stationary double-headed positron
      emission tomography (PET) camera, and the biodistribution was assessed by ex vivo
      determination of radioactivity in several tissues and different brain areas. One
      hour after injection of the radioligand, the bladder, kidney, liver, trachea, and
      bone of sADX animals contained more concentration on a wet weight basis than
      blood. Three hours post injection, radioactivity was retained in bladder,
      trachea, and bone. The accumulation of radioactivity in brain corresponded to the
      concentration of activity in the blood within the first hours after injection.
      ADX animals showed a higher uptake of 18F activity in spleen, testes, and brain
      areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET
      scans suggested that 18F activity uptake in the brain had not yet reached a
      maximum at this interval. Although [18F]Fluoro-Org 6141 is not useful for PET
      studies of glucocorticoid receptors (GRs), the results obtained with this
      compound indicate a synthetic strategy suitable for the synthesis of high
      affinity radioligands for GRs.

PMID- 8547888
TI  - [O-methyl-11C]beta-CIT-FP, a potential radioligand for quantitation of the
      dopamine transporter: preparation, autoradiography, metabolite studies, and
      positron emission tomography examinations.
AB  - beta-CIT-FP [N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4
      iodophenyl)nortropane] is a cocaine analogue with a high affinity for the
      dopamine transporter. [O-methyl-11C]beta-CIT-FP ([11C]beta-CIT-FP) was prepared
      by O-alkylation of the free acid with [11C]methyl iodide. The total radiochemical
      yield of [11C]beta-CIT-FP was 50 to 60% with an overall synthesis time of 30 min.
      The radiochemical purity was > 99%, and the specific radioactivity at time of
      injection was about 37 GBq/mumol (1000 Ci/mmol). Autoradiographic examination of
      [11C]beta-CIT-FP binding in human brain postmortem demonstrated specific binding
      in the caudate nucleus and putamen. Positron emission tomography (PET)
      examination of [11C]beta-CIT-FP in a Cynomolgus monkey demonstrated accumulation
      in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min.
      Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity
      ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5,
      respectively. In a displacement experiment, radioactivity in the striatum but not
      in the cerebellum was reduced after injection of beta-CIT, indicating that
      striatal radioactivity following injection of [11C]beta-CIT-FP is associated with
      dopamine transporter sites and that the binding is reversible. The fraction of
      the total radioactivity in plasma representing [11C]beta-CIT-FP determined by
      high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95
      min. [11C]beta-CIT-FP should be a useful PET radioligand for the quantitation of
      dopamine transporters in the human brain in vivo.

PMID- 8547890
TI  - Positron emission tomography in drug evaluation: influence of three different
      catechol-O-methyltransferase inhibitors on metabolism of [NCA] 6-[18F]fluoro-L
      dopa in rhesus monkey.
AB  - We compared the influence of three different catechol-O-methyltransferase (COMT)
      inhibitors (CGP 28014, OR-611 and Ro 40-7592) on the metabolism of no-carrier
      added (NCA) 6-[18F]fluoro-L-dopa (6-FDOPA) in one Rhesus monkey. All three COMT
      inhibitors improved 6-FDOPA availability in plasma, increased the specific uptake
      in the brain and thus improved 6-FDOPA uptake measurements using positron
      emission tomography (PET). Best results were obtained with Ro 40-7592.

PMID- 8547891
TI  - 123I-labeling and evaluation of Ro 43-0463, a SPET tracer for MAO-B imaging.
AB  - Using the copper assisted halogen exchange the MAO-B inhibitor Ro 43-0463, N-(2
      aminoethyl)-5-iodo-2-pyridinecarboxamide, was labelled with 123I as well as with
      125I to allow in vitro and in vivo investigations including SPET with healthy
      volunteers. Ro 43-0463 is known to inhibit reversibly and specifically MAO-B,
      having an IC50 of 3 x 10(-8) Mol/L. The labeling in the presence of CuSO4 and
      ascorbic acid was optimised, varying time (30 to 105 min), precursor
      concentration (1-3.5 mg) and temperature (130-200 degrees C). The labeling yield
      ranged between 60 and 70%. Purification was achieved with Lichrosorb RP-18 (5
      micron, 250 x 8 mm) and 1.5 mL/min 0.36 M H3PO4/EtOH 97/3 [0.01 M (NH4)2HPO4].
      After neutralisation and sterile filtration the final activity concentration
      ranged between 18.5 and 37 MBq/mL. Biodistribution studies showed a brain to
      blood ratio greater than 1 within 1 h p.i. The main radiation burden calculated
      from these animal data is to alimentary and excretory organs and the ovaries.
      Autoradiography was performed using rat brain slices and 5 nM [125I]Ro 43-0463 in
      TRIS-buffer pH 7.4 for 90 min at 20 degrees C. Its radioactivity pattern
      corresponds to the known distribution of MAO-B in the rat brain. By displacement
      with L-deprneyl the highly specific binding of R0 43-0463 was proven in vitro.
      SPECT studies with normal volunteers corresponded with the pattern found in
      autoradiography.

PMID- 8547892
TI  - Evaluation of the biodistribution and in vivo biochemistry of 99mTc-cysteine and
      99/99mTc-cysteine complexes--a potential renal imaging agent.
AB  - Cysteine was chelated with 99mTc and/or 99Tc in a freeze-dried kit containing
      Tin(II) ions, and the yellow 99m/99Tc-cysteine complex (complex I) was separated
      to study the biodistribution. Comparison of the distribution of 99m/99Tc-cysteine
      and 99mTc-cysteine complexes was made in rats and mice. The renal excretion
      patterns were studied in rats in the presence and absence of the renal tubular
      transport inhibitor 2,4-dinitrophenol. The carrier of Tc-cysteine complex in the
      blood and also the radioactive compounds in the urine were studied by HPGFC and
      SDS-electrophoresis. The kidney was confirmed as the target organ; serum albumin
      serves as a carrier for transport of Tc-cysteine complex to the kidney. The Tc
      cysteine complex was the primary form in excreta, and glomerular filtration was
      the dominant excretory pathway.

PMID- 8547893
TI  - Preparation and biological behaviour of 99mTc-carbonyl and 99mTc-nitrido
      complexes of cysteine and some cysteine esters.
AB  - The preparation of 99mTcO-, 99mTcN- and 99mTc(CO)-complexes of cysteamine (CYA),
      cysteine (CYS) and the methyl (CME) and ethyl (CEE) esters of cysteine is
      described. All complexes were stable and their biological behaviour in mice was
      studied. Most complexes were found to clear predominantly via the renal pathway
      with TcN- and Tc(CO)-complexes exhibiting greater urinary clearance than the
      corresponding TcO-complex. 99mTcN-CME, 99mTc(CO)-CME and 99mTc(CO)-CYS were found
      to be rapidly cleared via the kidneys and the effect of probenicid on renal
      clearance was studied to determine whether tubular excretion was involved. The
      results suggest that tubular secretion is involved in the renal clearance of
      99mTcN-CME and Tc(CO)-CYS.

PMID- 8547894
TI  - Generator eluate effects on the labeling efficiency of 99mTc-sestamibi.
AB  - Our nuclear pharmacy noted that 99mTc-sestamibi kits sometimes failed
      radiochemical purity (RCP) testing (i.e., RCP < 90%). All failed kits had been
      prepared with eluate from a newly arrived generator (ingrowth time > or = 72 h)
      which had been eluted > or = 6 h before the kit failure. The effects of 99mTc
      activity and eluate volume were then investigated to help explain the reason for
      the low RCP values. Our results demonstrated that higher failure rates of the
      99mTc-sestamibi kits were noted when higher activities of 99mTc eluates were
      added, and the higher failure rates of the kits were associated with lower RCP
      values. In addition, higher kit failure rate and lower RCP values of the 5.55-GBq
      kits at 12 h postelution in comparison with the 11.1-GBq kits at 6 h (same eluate
      volume) indicated that the 99mTc activity and volume had a less detrimental
      effect on the 99mTc-sestamibi kit preparation than the 99mTc eluate age. The kit
      failures might be explained by the higher amount of 99mTc and the production of
      the free radicals during the long ingrowth time prior to generator elution. In
      conclusion, the use of a first elution from a long-ingrowth time generator at a
      later stage (i.e., 11.1 GBq at 6 h and 5.55 GBq at 12 h postelution) in
      preparation of a 99mTc-sestamibi kit is associated with a high rate of kit
      failure and should therefore be avoided.

PMID- 8547895
TI  - Radiolabeling and biodistribution of amiodarone and desethylamiodarone.
AB  - The antiarrhythmic drug amiodarone and its metabolite desethylamiodarone, were
      radiolabeled with sodium [123I]-iodide in > 98% yield using the exchange labeling
      method. Biodistribution studies with 123I-amiodarone in mice showed high liver
      and lung uptake. Heart uptake of 0.98% of the injected dose (id) peaked at 5 min,
      with clearance seen over 60 min to 0.44% id. 123I-Desethylamiodarone (123I-DEA)
      showed heart uptake of 0.58% id peaking at 5 min, with slower clearance seen over
      60 min to 0.43% id. These results indicate that both agents have poor selectivity
      as myocardial imaging tracers. Low 123I-DEA brain uptake at 5 min (0.49% id) and
      rapid washout after 60 min indicate that 123I-desethylamiodarone has limited
      application as a brain imaging agent.

PMID- 8547897
TI  - Delivering medical information to the desktop: the UIC GRATEFUL-MED-via-the
      Internet experience.
AB  - The University of Illinois at Chicago (UIC) provides the campus community,
      including the main campus and three regional sites, with a local MEDLINE option
      through a GRATEFUL MED fixed-fee licensing agreement with the National Library of
      Medicine. Searching is available via the Internet. A password server and
      customized GRATEFUL MED clients were built in order to adapt this off-the-shelf
      product to match the look and feel of other UIC campus-wide Internet resources.
      Installation, documentation, and training issues affecting the success of the
      project are discussed.

PMID- 8547896
TI  - The health sciences librarian as Internet navigator and interpreter.
AB  - Over the past several years, thousands of networked information resources have
      become available to individuals and institutions with access to the Internet.
      Unfortunately, the dizzying array of computing and networking environments often
      frustrates end users' attempts to navigate the Internet. Librarians have begun to
      take responsibility not only for instructing users in the use of basic network
      tools such as file transfer, remote log-in, and electronic mail, but also for
      answering questions concerning network access and even information system design.
      The authors show how, by continuing to adapt to this new and volatile
      environment, health sciences librarians find themselves playing increasingly
      important roles in shaping the information policies and practices of their
      institutions. To illustrate these new roles, the authors review the experiences
      of health sciences librarians at the University of California, Los Angeles, and
      the University of California, San Diego. These institutions have varying and
      complex networking environments, and their biomedical libraries have taken lead
      roles in clarifying and interpreting their particular Internet features.

PMID- 8547898
TI  - Strengthening the links between health sciences information users and providers.
AB  - In 1994, the Hospital Library Service Program of the Central New York Library
      Resources Council conducted a study to evaluate the usefulness, impacts, and
      potential services of eleven hospital libraries in a four-county area in New York
      State; determine the degree to which the libraries comply with Joint Commission
      on Accreditation of Healthcare Organizations (JCAHO) standard IM.9.2; and provide
      recommendations for improved services in the member libraries. Two research
      instruments were used: a survey for hospital-based health sciences professionals
      and a survey for hospital-based information providers. Results from the two
      surveys were compared to determine if users' needs were being filled, and to
      develop plans for improved information services and products. Fourteen
      recommendations are made that, if implemented, will support the creation of user
      defined information products, enhance the library's profile within the hospital,
      and exploit resource sharing to reduce costs and enhance coordination.

PMID- 8547899
TI  - Educational services in health sciences libraries: a content analysis of the
      literature, 1987-1994.
AB  - The recent literature (1987-1994) describing educational services of health
      sciences librarians was analyzed for content. Variables examined included
      publication journal, country, type of article (description, review, or advocacy),
      target audience of education services, and subject of article. Articles that
      reported research results also were identified. Of 123 articles studied, 82.1%
      were descriptive, 14.6% advocacy, and 3.3% reviews. Library users were the
      primary target audience (85.1%), an increase over the percentage reported in an
      earlier study of the 1975-1986 literature. Librarians were the target audience in
      12.8% of the articles, a decrease from the previous study's findings. There was
      an increase in educational offerings by academic libraries, which sponsored 83.2%
      of programs, while hospital libraries' sponsorship decreased to 5% of programs
      reported in the literature. The analysis identified a major need for research
      related to educational activities in health sciences libraries.

PMID- 8547900
TI  - The impact of medical libraries and literature on patient care in New Zealand.
AB  - This paper reports the results of a survey of 372 physicians working in regional
      hospitals in New Zealand. The survey was undertaken to determine if these
      physicians used their local medical library and what impact the literature
      obtained had on patient care. The 295 respondents (80.6% of the sample) expressed
      genuine interest in their library, with most visiting the library once a week or
      more. Patient care was ranked as the main reason for their visit; the second most
      important reason was keeping up-to-date on the latest research. Physicians
      indicated that information obtained at the library was used to confirm or change
      diagnoses, medications, or diagnostic tests, or to change advice given to
      patients. Information also was used to make decisions concerning early discharge,
      avoidance of hospital admission, or transfer of patients to another hospital. The
      survey also addressed the use of librarian services, sources of information used,
      and physicians' purchase of textbooks and journals. All comments by respondents
      were supportive of the library. The significance of libraries to clinical
      decision making, especially in small hospitals, is discussed.

PMID- 8547901
TI  - From task force to statute: establishing health sciences libraries in state law
      as a component of the health care system.
AB  - This paper describes how Montana librarians successfully incorporated health
      sciences libraries into the statewide health care resource management plan being
      developed under 1993 state law. First, a broad-based Montana Task Force for
      Biomedical Information was formed with funds from the National Network of
      Libraries of Medicine/Pacific Northwest Region and the Montana Area Health
      Education Center. The resulting report reviewed findings from national studies
      and trends to current state developments and deficiencies. The report was
      presented to the governor and state legislators in the context of cost
      containment measures being considered in the state's health care reform bill. Now
      Montana law provides that "it is further the policy of the state of Montana that
      the health care system should ... facilitate universal access to current health
      sciences information," and "The management plan must include ... identification
      of the current supply and distribution of ... health sciences library resources
      and services." This experience highlights the need for health sciences librarians
      to develop skills in advocacy, lobbying, and networking with other components of
      the health care industry.

PMID- 8547902
TI  - Multiple usage of the CD PLUS/UNIX system: performance in practice.
AB  - In August 1994, the CD PLUS/Ovid literature retrieval system based on UNIX was
      activated for the Faculty of Medicine and Health Sciences of Erasmus University
      in Rotterdam, the Netherlands. There were up to 1,200 potential users. Tests were
      carried out to determine the extent to which searching for literature was
      affected by other end users of the system. In the tests, search times and
      download times were measured in relation to a varying number of continuously
      active workstations. Results indicated a linear relationship between search times
      and the number of active workstations. In the "worst case" situation with sixteen
      active workstations, the time required for record retrieval increased by a factor
      of sixteen and downloading time by a factor of sixteen over the "best case" of no
      other active stations. However, because the worst case seldom, if ever, happens
      in real life, these results are considered acceptable.

PMID- 8547903
TI  - The anatomy of a World Wide Web library service: the BONES demonstration project.
      Biomedically Oriented Navigator of Electronic Services.
AB  - In 1994, the John A. Prior Health Sciences Library at Ohio State University began
      to develop a World Wide Web demonstration project, the Biomedically Oriented
      Navigator of Electronic Services (BONES). The initial intent of BONES was to
      facilitate the health professional's access to Internet resources by organizing
      them in a systematic manner. The project not only met this goal but also helped
      identify the resources needed to launch a full-scale Web library service. This
      paper discusses the tasks performed and resources used in the development of
      BONES and describes the creation and organization of documents on the BONES Web
      server. The paper also discusses the outcomes of the project and the impact on
      the library's staff and services.

PMID- 8547904
TI  - Information-seeking practices of dental hygienists.
AB  - This paper reports on a survey of the information-seeking, critical-analysis, and
      computer-application practices of dental hygienists. Questionnaires were mailed
      to a convenience sample of seventy-one dental hygiene practitioners. A 62%
      response rate was achieved. Results indicated that discussions with colleagues,
      continuing education courses, journals, and newsletters were the sources used
      most frequently for professional development and information retrieval. To
      evaluate professional information, these hygienists tended to rely on personal
      experience, credibility of the journal, and discussions with colleagues. Word
      processing was the most frequently used computer application; online database
      searching was rare in this group. Computer used within the employment setting was
      primarily for business rather than clinical applications. Many hygienists were
      interested in attending continuing education courses on use of computers to
      acquire professional information.

PMID- 8547905
TI  - The impact of IAIMS on the work of information experts. Integrated Advanced
      Information Management Systems.
AB  - Integrated Advanced Information Management Systems (IAIMS) programs differ but
      have certain characteristics in common. Technological and organizational
      integration are universal goals. As integration takes place, what happens to
      those implementing the vision? A survey of 125 staff members, or information
      experts, involved in information or informatics at an IAIMS-funded institution
      was conducted during the last year of the implementation phase. The purpose was
      to measure the impact of IAIMS on the jobs of those in the library and related
      service units, and the computing, telecommunications, and health informatics
      divisions. The researchers used newly developed scales measuring levels of
      integration (knowledge of and involvement with other departments), customer
      orientation (focus on the user), and informatedness (changes in the nature of
      work beyond automation of former routines). Ninety-four percent of respondents
      indicated that their jobs had changed a great deal; the changes were similar
      regardless of division. To further investigate the impact of IAIMS on librarians
      in particular, a separate skills survey was conducted. The IAIMS librarians
      indicated that technology and training skills are especially needed in the new,
      integrated environment.

PMID- 8547906
TI  - Librarian participation in meta-analysis projects.
AB  - Meta-analysis is an epidemiological and statistical tool used to combine the
      results of independent studies and synthesize their conclusions for the purpose
      of evaluating therapeutic effectiveness, determining procedural efficacy, or
      providing a basis for development of treatment protocols. Meta-analysis also may
      be described as "studying the studies." The process, however defined, requires
      access to a large quantity of medical literature and presents new opportunities
      for medical librarians to use their data gathering skills. At Dartmouth Hitchcock
      Medical Center, a librarian assists with the identification, location, and review
      of literature in support of meta-analysis projects done by the Technology
      Assessment Program. Comprehensive literature searches are performed and
      references with abstracts, indexing terms, and other elements of the unit record
      are downloaded, converted, and presented as records in a database program.
      References are then analyzed, decisions are made about their relevance, and
      article copies are acquired for further analysis.

PMID- 8547907
TI  - Library faculty role in problem-based learning: facilitating small groups.
AB  - Since 1986, the library faculty of the McGoogan Library of Medicine at the
      University of Nebraska Medical Center (UNMC) has participated in small group
      activities during the week-long orientation for first-year medical students. This
      involvement paved the way for library faculty members to act as facilitators for
      small groups of medical students within the new problem-based learning (PBL)
      curriculum introduced in 1992 by the College of Medicine. The UNMC curriculum
      consists of traditional PBL groups as well as Integrated Clinical Experience
      (ICE) small groups. The ICE groups provide opportunities for discussion of the
      social and behavioral issues that arise in medicine, with the majority of the
      sessions designed to give students interviewing practice with simulated patients.
      The ICE small groups meet once a week with either one or two facilitators.
      Several library faculty members act as facilitators for ICE groups. As a result
      of this involvement, librarian contacts with College of Medicine faculty have
      grown in number and depth, there has been a corresponding increase in related
      activities with the first- and second-year medical students. Participation in ICE
      groups has caused some difficulties with respect to library work schedules, but
      it has been immensely rewarding and enriching in terms of professional growth.
      This paper describes the UNMC curriculum, the evolution and extent of the
      librarians' involvement, and the future involvement, ramifications, and
      challenges envisioned for McGoogan faculty and their medical library colleagues.

PMID- 8547908
TI  - "Librarian for hire": contracting a librarian's services to external departments.
AB  - In a time of financial constraints, Harvard Medical School's Countway Library has
      found a way to acquire additional funding to expand its services while
      integrating librarians further into the medical school organization. This paper
      describes the contractual arrangement between the library and a medical school
      department and shows how a professional librarian can be integrated into the
      institutional environment and take on new roles that are both meaningful and
      satisfying. As liaison to the curriculum development department of the medical
      school, the librarian was involved in curriculum planning, software support, and
      computing facility support. Increased understanding and cooperation has evolved
      between the contracting departments, and the problems encountered by the liaison
      have been minor. The contractual arrangement was not only successful but also
      provided a model for future outreach projects.

PMID- 8547909
TI  - The application of health sciences library skills in other settings.
AB  - Medical librarians have been urged to assume personal responsibility for seeking
      lifelong education and professional development opportunities, but it is not
      always clear which opportunities should be sought or which skills will be needed
      in the rapidly changing health sciences environment. To shed some light on these
      issues, the author interviewed former medical librarians from southern California
      and Arizona who are now employed in other settings, to determine the skills that
      aided their transition from the medical library arena to new jobs. In interviews,
      respondents highlighted the importance of presentation, training, management,
      reference, computer, and interpersonal skills. Although both technical and
      interpersonal skills aided successful transitions, strong interpersonal skills
      augmented technical abilities and may be essential to successful career change.
      In sum, medical librarians possess skills that transfer well to other settings.
      Individuals with clear career goals who are able to present themselves and their
      skills well can take advantage of career opportunities, in both new settings and
      in medical libraries.

PMID- 8547910
TI  - Scientific writing and editing: a new role for the library.
AB  - Traditional library instruction programs teach scientists how to find and manage
      information, but not how to report their research findings effectively. Since
      1990, the William H. Welch Medical Library has sponsored classes on scientific
      writing and, since 1991, has offered a fee-based editing service for affiliates
      of the Johns Hopkins Medical Institutions. These programs were designed to fill
      an educational gap: Although formal instruction was offered to support other
      phases of the scientific communication process, the medical institutions had no
      central resource designed to help scientists develop and improve their writing
      skills. The establishment of such a resource at Welch has been well received by
      the community. Attendance at classes has grown steadily, and in 1993 a credit
      course on biomedical writing was added to the curriculum. The editing service,
      introduced in late 1991, has generated more requests for assistance than can be
      handled by the library's editor. This service not only extends the library's
      educational outreach but also generates a revenue stream. The Welch program in
      scientific writing and editing, or elements of it, could provide a model for
      other academic medical libraries interested in moving in this new direction.

PMID- 8547911
TI  - Medical education and faculty development: a new role for the health sciences
      librarian.
AB  - This paper describes the roles and responsibilities of the associate director for
      medical education at the Primary Care Resource Center (PCRC), School of Medicine
      and Biomedical Sciences, State University of New York at Buffalo (UB). The PCRC
      was established to increase the number of UB medical school graduates who
      selected graduate medical education in the generalist disciplines. The associate
      director, who is a health sciences librarian, has established collaborative
      working relationships with primary care physicians in the clinical departments of
      family medicine, pediatrics, and internal medicine with the goal of improving the
      teaching effectiveness of faculty and residents. Another goal is to incorporate
      the use of computerized information technologies into clinical practice by
      training physicians and residents, at specially equipped ambulatory training
      sites, in how to access and manage information for the purpose of providing
      quality medical care. This has been accomplished in part through the provision of
      highly personalized instruction to participants. In addition to describing these
      activities, this paper examines how the duties of the associate director reflect
      the potential for long-term change in the roles and responsibilities of health
      sciences librarians, whether they work in a traditional or nontraditional
      setting.

PMID- 8547912
TI  - Highlighting emerging roles and enduring values: information management in
      nursing education.

PMID- 8547913
TI  - Multilevel library instruction for emerging nursing roles.
AB  - As new nursing roles emerge that involve greater decision making than in the
      past, added responsibility for outcomes and cost control, and increased emphasis
      on primary care, the information-seeking skills needed by nurses change. A search
      of library and nursing literature indicates that there is little comprehensive
      library instruction covering all levels of nursing programs: undergraduate,
      returning registered nurses, and graduate students. The University of Florida is
      one of the few places that has such a multilevel, course-integrated curriculum in
      place for all entrants into the nursing program. Objectives have been developed
      for each stage of learning. The courses include instruction in the use of the
      online public access catalog, printed resources, and electronic databases. A
      library classroom equipped with the latest technology enables student interaction
      with electronic databases. This paper discusses the program and several methods
      used to evaluate it.

PMID- 8547914
TI  - The librarian as a partner in nursing education.
AB  - Welch Medical Library has explored new roles for librarians in knowledge
      management instruction programs throughout the Johns Hopkins University School of
      Nursing curricula. These programs have created roles for library staff as both
      instructors and knowledge management experts. By fostering strong communication
      and attention to quality instruction, librarians achieved their vision of a
      program in knowledge management integrated into the curriculum, where they are
      partners working with nursing faculty to define the students' knowledge
      management needs and decide how these needs can be met.

PMID- 8547915
TI  - Citation analysis of faculty publication: beyond Science Citation Index and
      Social Science Citation Index.
AB  - When evaluated for promotion or tenure, faculty members are increasingly judged
      more on the quality than on the quantity of their scholarly publications. As a
      result, they want help from librarians in locating all citations to their
      published works for documentation in their curriculum vitae. Citation analysis
      using Science Citation Index and Social Science Citation Index provides a logical
      starting point in measuring quality, but the limitations of these sources leave a
      void in coverage of citations to an author's work. This article discusses
      alternative and additional methods of locating citations to published works.

PMID- 8547916
TI  - Reference librarians' perceptions and use of Internet resources: results of a
      survey of academic health sciences libraries.

PMID- 8547917
TI  - Online SERHOLD updating for the Pacific Northwest.

PMID- 8547918
TI  - Ruling handed down on Texaco appeal.

PMID- 8547919
TI  - Outbreak of toxoplasmosis associated with municipal drinking water--British
      Columbia. The British Columbia Toxoplasmosis Team.

PMID- 8547921
TI  - African pygmy hedgehog-associated salmonellosis--Washington, 1994.

PMID- 8547920
TI  - The Ebola fever epidemic officially declared over in Zaire.

PMID- 8547922
TI  - What is rurality?

PMID- 8547923
TI  - Qualitative differences between urban and rural practice.

PMID- 8547924
TI  - Workload: changes and trends.

PMID- 8547925
TI  - Balancing proactive and reactive care.

PMID- 8547926
TI  - Teamwork in rural practice.

PMID- 8547927
TI  - Obstetrics in rural practice: problem or solution?

PMID- 8547928
TI  - Rural deprivation.

PMID- 8547929
TI  - Healthy villages.

PMID- 8547930
TI  - Community hospitals.

PMID- 8547931
TI  - Education for rural primary health care workers.

PMID- 8547932
TI  - Peripatetic medical societies.

PMID- 8547933
TI  - Recruitment to rural practice.

PMID- 8547934
TI  - Rural general practice: international perspectives.

PMID- 8547935
TI  - Health needs of rural residents.

PMID- 8547936
TI  - Fluid-electrolyte balance associated with tennis match play in a hot environment.
AB  - Twenty (12 male and 8 female) tennis players from two Division I university
      tennis teams performed three days of round-robin tournament play (i.e., two
      singles tennis matches followed by one doubles match per day) in a hot
      environment (32.2 +/- 1.5 degrees C and 53.9 +/- 2.4% rh at 1200 hr), so that
      fluid-electrolyte balance could be evaluated. During singles play, body weight
      percentage changes were minimal and were similar for males and females (males 
      1.3 +/- 0.8%, females -0.7 +/- 0.8%). Estimated daily losses (mmol.day-1) of
      sweat sodium (Na+) and potassium (K+) (males, Na+ 158.7, K+ 31.3; females, Na+
      86.5, K+ 18.9) were met by the players' daily dietary intakes (mmol.day-1) of
      these electrolytes (males, Na+ 279.1 +/- 109.4, K+ 173.5 +/- 57.7; females, Na+
      178.9 +/- 68.9, K+ 116.1 +/- 37.5). Daily plasma volume and electrolyte (Na+, K+)
      levels were generally conserved, although, plasma [Na+] was lower (p < .05) on
      the morning of Day 4. This study indicated that these athletes generally
      maintained overall fluid-electrolyte balance, in response to playing multiple
      tennis matches on 3 successive days in a hot environment, without the occurrence
      of heat illness.

PMID- 8547937
TI  - Glucose and insulin responses after commonly used sport feedings before and after
      a 1-hr training session.
AB  - This investigation examined the plasma glucose and insulin response in 6 trained
      athletes after consumption of four commercially available sport feedings 2 hr
      before as well as immediately after 1 hr of running under common training
      conditions. Four feedings were compared: Feeding 1, 160 g CHO/400 ml; Feeding 2,
      69 g CHO/400 ml; Feeding 3, 69 g CHO + 6 g protein/400 ml; and Feeding 4, solid
      69 g CHO + 5 g protein + 4 g fat. Before the training session, there were no
      differences between the four sport feedings in the area under the glucose and
      insulin curves and the insulin/glucose ratio. However, after exercise, Feeding 2
      resulted in a significantly greater area under the glucose curve compared with
      Feedings 1, 3, and 4 (respectively, 352 vs. 241, 251, and 182) and a
      significantly lower insulin/glucose ratio compared with Feeding 1 (respectively,
      6.2 vs. 15.8). Therefore, it is concluded that the kind of sport feeding may
      influence postexercise glucose and insulin responses.

PMID- 8547938
TI  - An assessment of carbohydrate intake in collegiate distance runners.
AB  - To determine the extent to which well-trained endurance athletes practice the
      dietary recommendations for maximizing muscle glycogen resynthesis, collegiate
      cross-country runners (14 males and 10 females) kept 4-day dietary and activity
      records during a training period and a competitive period in the regular cross
      country season. The mean running mileages for men and women were 16.0 +/- 1.0 and
      10.7 +/- 0.6 km/day during the training period and 14.6 +/- 0.8 and 8.7 +/- 0.5
      km/day during the competitive period, respectively. Males reported adequate
      energy intake in both phases, whereas females fell short of the RDA. However, the
      percentage of calories from carbohydrate was found to be inadequate (< 60%) for
      male runners. Although female runners derived 65-67% of calories from
      carbohydrate, the daily amount of carbohydrate taken was insufficient (< 10 g/kg
      body weight). Carbohydrate was ingested immediately postexercise approximately
      50% of the time or less, with even far less taken in suggested quantities
      (approximately 1 g carbohydrate/kg body weight). There were no significant
      differences in dietary trends between training and competitive phases. The
      results suggest that these endurance athletes were not practicing the recommended
      feeding regimen for optimal muscle glycogen restoration.

PMID- 8547939
TI  - Effects of carbohydrate feeding before and during prolonged exercise on
      subsequent maximal exercise performance capacity.
AB  - The study examined the effect of carbohydrate ingestion on exercise performance
      capacity. Nine male cyclists performed two separate trials at 70% VO2max for 60
      min followed by a maximal ride for 10 min. During trials subjects were fed either
      an 8% glucose solution (CHO) or a placebo solution (PL), which were administered
      at rest and during and immediately after submaximal exercise. Statistical
      analyses indicated that glucose levels at rest increased significantly 15 min
      after the ingestion of CHO compared to PL. At 30 and 60 min during submaximal
      exercise, plasma glucose levels decreased significantly in the CHO but not in the
      PL trial. Following the performance ride, glucose levels increased significantly
      only during the CHO test trial. Free fatty acids did not change significantly
      during testing trials. The maximal performance ride results showed that in the
      CHO trial, a significantly greater external work load was accomplished compared
      to the PL trial. It is concluded that CHO ingestion improves maximal exercise
      performance after prolonged exercise.

PMID- 8547940
TI  - Dietary intake of female collegiate heavyweight rowers.
AB  - The purpose of this study was to evaluate the adequacy of dietary intake in 16
      female heavyweight rowers during the sprint racing phase of the season. Caloric
      intake for the rowers was 2,633 kcal/day, lower than expected given the training
      regimen of these athletes. On average, rowers consumed below-optimal levels of
      carbohydrate. Protein intake was satisfactory but fat intake was higher than
      recommended. For the majority of rowers, micronutrient intake met the RDA.
      However, calcium, zinc, B6, and B12 fell short of meeting two-thirds of the RDA
      for a significant percentage of rowers. The preevent meal consumed both 15 hr and
      2 hr before the event provided less carbohydrate and fluid but more fat than
      desirable. Female heavyweight rowers would benefit from nutritional counseling
      that provides strategies for increasing complex carbohydrates, calcium, zinc, B6,
      and B12 while reducing dietary fat. Adequate fluid intake is also essential.

PMID- 8547941
TI  - High school athletes and nutritional supplements: a study of knowledge and use.
AB  - Factors influencing nutritional supplement use by high school students were
      assessed. Comparisons were made between various groups of sports participants and
      non-sports participants. The Nutritional Supplement Use and Knowledge Scale was
      administered to 509 students. Mean supplement use score was 10.87 (SEM = 0.50,
      range 0-57). Mean knowledge score was 13.56 (SEM = 0.16, range 1-21). Significant
      relationships (p < .01) were obtained for supplement knowledge with use, and
      supplement use with gender. ANOVA found significant differences between
      supplement use by gender (p < .01), supplement use by sports category (p < .05),
      and knowledge scores by sports category (p < .01). Discriminant function analysis
      indicated knowledge, supplement use, and subscores for protein,
      vitamins/minerals, knowledge, supplement use, and subscores for protein,
      vitamins/minerals, and carbohydrates were best discriminators of sport group
      membership. Greater knowledge about supplements was associated with less use;
      hence, education about supplements can be a deterrent to use. This study may help
      coaches, athletic trainers, athletic directors, teachers, physicians, and parents
      identify nutritional misconceptions held by adolescents.

PMID- 8547942
TI  - Effects of activin-A on neurons acutely isolated from the rat supraoptic nucleus.
AB  - Nerve fibers containing activin-like immunoreactivity have been shown to be
      present within the area of the supraoptic nucleus. In this study, whole-cell
      patch-clamp recordings from supraoptic magnocellular neurosecretory cells were
      used to characterize the electrophysiological effects of this peptide. Nanomolar
      concentrations of recombinant activin-A caused the appearance of a voltage
      independent current reversing near -40 mV. At resting potential, membrane
      depolarization caused by this current was sufficient to accelerate action
      potential discharge, suggesting that activin receptors expressed on magnocellular
      neurosecretory cells may play a role in the control of neurohypophysial hormone
      release.

PMID- 8547943
TI  - Glial ensheathment of GnRH neurons in pubertal female rhesus macaques.
AB  - During the period of development, prior to full sexual maturity, gonadotropin
      hormone-releasing hormone (GnRH) neurons are fully capable of synthesizing and
      processing the GnRH decapeptide. Nonetheless, the secretion of the hormone is not
      adequate to stimulate adult patterns of gonadotropin release. The present study
      was undertaken to examine ultrastructural characteristics of the GnRH neuron and
      its relationship to its environment in early-midpubertal female rhesus monkey.
      The neurons bore all the ultrastructural immunocytochemical characteristics of
      those in mature animals, but quantitative morphometrics revealed that they were
      extensively apposed by glial processes. Such ensheathment was described earlier
      in ovariectomized adult animals and was found to be reversible by administration
      of gonadal steroids. The density of synaptic input to GnRH neurons in the
      pubertal animals did not differ significantly from that of adult intact or
      ovariectomized animals from a previous study. Chemical identification will be
      required to determine whether there are age or hormonal differences in the
      innervation of these neurons. These results provide anatomical evidence in
      support of indications from other studies that the ovarian steroidal milieu
      affects GnRH-glial relationships. Further testing will be required to determine
      whether the attainment of sexual maturity in the female rhesus macaque is
      dependent upon a reduction in glial ensheathment of GnRH neurons.

PMID- 8547944
TI  - A technique for sorting rat gonadotropes using anti-LH or anti-FSH antibodies
      covalently attached to magnetic beads.
AB  - A technique for sorting live LH- and FSH-secreting cells was developed. After
      enzymatic dispersion, a suspension of pituitary cells from male rats castrated 7
      days earlier was incubated in potassium chloride (KCI 50 mmol/l) for 30 min and
      gonadotropin outflow was provoked. Then, considering either LH or FSH as
      temporary surface markers, we positively selected the secreting cells by means of
      antibodies toward either LH (anti-LH beads) or FSH (anti-FSH beads) covalently
      attached to magnetic beads. The spontaneous secretion of LH and FSH overnight and
      the release induced by KCI the following morning were calculated. A population
      enriched in gonadotropes (16% of the total) able to secrete both gonadotropins
      was selected by means of anti-LH beads; this released 7 times as much LH as non
      selected cells. A similar population (14% of the total) was selected by means of
      anti-FSH-coated beads; this produced 3.3 times as much LH as non-selected cells.
      In some experiments, the cells not previously sorted with anti-LH-coated beads
      were further incubated in the presence of anti-FSH beads, in an attempt to
      isolate a population secreting only FSH. A limited number of cells were sorted
      (6% of the total cells), able to produce both gonadotropins, but with a lower
      LH/FSH ratio. Similarly, those cells excluded by the selection with anti-FSH
      beads were further incubated with anti-LH beads, with a view to obtaining only-LH
      secreting cells. However, both gonadotropins were still secreted by these cells
      (8% of the total), which had the highest LH/FSH ratio. In conclusion, fractions
      from castrated male rats that are enriched in gonadotropes contain cells that
      secrete both gonadotropins in vitro. The secretion of LH is prevalent. However,
      differences in the LH/FSH ratio between the populations sorted and changes from
      spontaneous to stimulated release are observed. This suggests that some
      gonadotropes might 'specialize' in releasing LH and others in releasing both LH
      and FSH.

PMID- 8547945
TI  - Annual variations of in vitro GNRH release by hypothalamic explants in intact and
      castrated male mink: relations with LH, FSH and testosterone circulating serum
      levels.
AB  - In mink, a short-day breeder, testis growth begins in autumn (November), reaches
      a maximum in February, before matings occur, and decreases from March to very low
      volumes during spring and summer. To study the effects of season and testosterone
      feedback on gonadotrophin and GnRH secretion, the annual variations of LH, FSH,
      testosterone and GnRH were studied in intact and castrated mink. As portal blood
      sampling raised serious difficulties, an in vitro static incubation system was
      used for studying GnRH variations. In intact mink, serum LH concentrations did
      not vary significantly throughout the year, whereas FSH concentrations increased
      significantly between September and November then decreased to a minimum in
      January. Testosterone values rose significantly from November to a maximum from
      January to March, decreased very rapidly thereafter. Castration in November
      resulted in a significant increase in LH and FSH concentrations which remained
      higher than the values measured in intact males throughout the year. In long-term
      castrated mink, FSH concentrations did not fluctuate during the year, whereas LH
      concentrations showed an annual variation, with high values in April and August.
      For the study of in vitro GnRH liberation, medio-basal hypothalamic explants were
      incubated in Krebs-Ringer phosphate buffer for 3 periods of 15 min, and
      stimulated with copper complexed equimolarly with histidine (Cu/His, 200 microM)
      and prostaglandin E2 (PGE2, 10 microM). After Cu/His, the release of GnRH was 1
      to 4 fold the basal release; after PGE2, the increase was 4-7 fold the basal
      release. The basal release of GnRH increased significantly between September and
      October to reach a maximum in November, decreased significantly in December to a
      minimum in February then increased progressively from May. The release of GnRH
      stimulated by Cu/His and PGE2 showed the same seasonal variation as the basal
      release. Castration 8 days before the sacrifice did not alter the release of
      GnRH, except in December: the release stimulated by PGE2 was then higher in
      intact than in castrated mink. Taken together, these results indicate that, with
      an in vitro static incubation system, it is possible to study the annual
      variations of GnRH release and to correlate these variations with those of serum
      gonadotrophin and testosterone concentrations. The synthesis and release of GnRH
      increased slightly from May, under long days, then more rapidly from September,
      resulting in an increased secretion of FSH in October, responsible for testis
      recrudescence. The annual pattern of basal and stimulated GnRH release was
      similar in intact and castrated mink, suggesting a direct effect of the season on
      the hypothalamus, rather than a negative feedback effect of the testis; however,
      testosterone seemed to feedback mainly at the pituitary level.

PMID- 8547946
TI  - Effect of parathyroid hormone and calcitonin on cholinergic markers in rat
      parathyroid gland.
AB  - The effect of parathyroid hormone (PTH) and calcitonin on 3H-choline uptake and
      on 3H-acetylcholine synthesis by rat parathyroid glands were examined. Incubation
      of tissue for 120 min with PTH or calcitonin resulted in an inverted bell-shaped,
      dose-dependent inhibition of 3H-choline uptake, with a maximal effect at 10(-9) M
      concentration. The effect of PTH on parathyroid choline uptake was blunted by
      preincubation with the PTH antagonist NLe(8-18)-PTH (3-34) amide. PTH brought
      about a dose-dependent inhibition of 3H-choline conversion to 3H-acetylcholine,
      with significant effects at 10(-8) M concentration or higher. This inhibitory
      effect of PTH on 3H-acetylcholine synthesis was blocked by co-incubation with the
      PTH antagonist NLe(8-18)-PTH (3-34) amide. Only at a 10(-7) M concentration
      calcitonin was effective to impair the in vitro conversion of radioactive choline
      into 3H-acetylcholine by parathyroid fragments. The results indicate that, in
      vitro, PTH, and to a less extent, calcitonin, inhibit cholinergic activity in rat
      parathyroid glands.

PMID- 8547947
TI  - Mechanism of action of pituitary adenylate cyclase-activating polypeptide (PACAP)
      in human nonfunctioning pituitary tumors.
AB  - Several evidence suggest that pituitary adenylate cyclase activating polypeptides
      (PACAP-38 and -27) could function as hypophysiotropic factors. Both peptides
      interact with either the type I receptor, which preferentially binds the two
      PACAPs and has a much lower affinity for vasoactive intestinal polypeptide (VIP)
      or the type II receptor, which binds the two PACAPs and VIP with a nearly equal
      affinity. In addition to the stimulation of adenylyl cyclase (AC) activity, in
      different cell types PACAP causes an increase of cytosolic calcium levels
      ([Ca2+]i), consequent to phospholipase-C activation. In the present study, we
      investigated the effect of PACAP on cAMP formation and [Ca2+]i levels in 16 human
      nonfunctioning pituitary adenomas (NFPA). PACAP-38 increased cAMP formation in
      all tumors; the peptide stimulated either AC activity in membrane preparations
      from 26 +/- 10 to 214 +/- 179 pmol/mg prot/min (P < 0.01) or cAMP efflux from 12
      +/- 5.4 to 73.2 +/- 32 pmol/well (P < 0.01) in cultured cells. The effect,
      detectable at concentrations higher than 1-10 pM, was maximal at 0.1-10 nM. While
      PACAP-38 and PACAP-27 were nearly equally effective and potent, 100-fold higher
      concentrations of VIP were required to obtain similar AC activation. GHRH and CRH
      were ineffective in any NFPA. The PACAP effect was not antagonized by a VIP
      antagonist, while PACAP fragment 6-27 amide partially reduced the stimulatory
      effects of both PACAP-27 and VIP in 2 out of 3 tumors tested. PACAP-38 caused a
      [Ca2+]i rise in cells obtained from 7 NFPA (from 110 +/- 34 to 151 +/- 40 nM
      [Ca2+]i, P < 0.05) while in the remaining 7 the peptide was ineffective at any
      concentrations tested (from 1 nM to 10 microM). In the responsive tumors, PACAP
      38 effect was not consequence of phospholipase-C activation since removal of
      extracellular Ca2+ as well as blockade of L-type Ca2+ channels by dihydropyridine
      antagonists abolished [Ca2+]i increase triggered by the peptide. These data
      indicate that PACAP is by far the most potent activator of cAMP formation in NFPA
      and suggest a possible modulatory action of this peptide on cell growth.

PMID- 8547948
TI  - Effects of continuous and repetitive administration of a potent analog of GH-RH(1
      30)-NH2 on the GH release in rats treated with monosodium glutamate.
AB  - To assess the efficacy of a potent GH-releasing hormone (GH-RH) analog (D
      Ala2,Nle27,Gaba30-GH-RH-(1-30)-amide) in the treatment of GH deficiency, we
      investigated the effects of chronic administration of this analog (A-495) on
      growth responses in monosodium glutamate (MSG)-lesioned rats. Basal serum GH
      concentrations, GH responses to bolus injections of GH-RH, as well as
      acceleration of body gain and linear growth were compared after long-term
      continuous and repetitive administration of A-495. The effects of continuous and
      repetitive administration of the analog on GH responses in vitro were also
      compared using the superfused pituitary cell system method. Treatment with MSG
      reduced the body weight and linear growth of the animals (-22% and -11%,
      respectively), the basal serum GH concentration (-66%), and the GH-RH-induced
      absolute GH responses (-61%) but did not alter the relative GH responses (to
      basal GH concentrations). Repetitive administration of 10 micrograms daily doses
      of A-495 at 24 h intervals for 2 weeks highly increased the GH responsiveness to
      GH-RH and induced catch-up growth, by which MSG-treated animals achieved the
      growth rate of normal controls. However, basal serum GH concentrations were only
      modestly enhanced. Continuous infusion of A-495 at the same daily dose resulted
      in slight increases in the GH-RH-induced GH rises, moderate acceleration of body
      gain, and no change in linear growth. Basal serum GH concentrations were not
      significantly influenced by this treatment. These results demonstrate that
      exogenous GH-RH pulses administered at lower frequency than the frequency of the
      physiological GH secretion are able to fully restore the normal growth rate of
      the GH deficient rats. The effectivity of the treatment is rather dependent on
      the magnitude of GH rises than the basal GH level. Although continuous
      administrations of the GH-RH is also have some effect on the body gain,
      repetitive administration is more effective at the same daily dose. Our results
      from in vitro experiments show that, in addition to the low magnitude of the GH
      RH-stimulated GH rises, desensitization of the GH secretory response might also
      be accounted for the low effectivity of the continuously administered GH-RH.
      Present results demonstrate the therapeutic usefulness of our new GH-RH analog
      and are the first to evidence that GH-RH need not be administered as frequently
      as the appearance of the endogenous GH pulses to restore the normal growth of the
      GH deficient rats.

PMID- 8547949
TI  - Distribution of androgen receptor-like immunoreactivity in the brains of
      cynomolgus monkeys.
AB  - A polyclonal antibody, PA1, raised in a rabbit against fusion proteins containing
      fragments of the human prostatic androgen receptor (AR) was used to map the
      distribution of AR-like immunoreactivity in the brains of adult male and female
      cynomolgus monkeys. PA1 AR-immunoreactive (ARir) labeling occurred in the cell
      nuclei and, more weakly, in the cytoplasm of brain cells. The PA1 ARir labeling
      occurred primarily in brain regions previously shown on the basis of gonadal
      steroid autoradiography to contain androgen receptors. However, the distribution
      of PA1 ARir staining was substantially more restricted than that of
      autoradiographic labeling using 3H-androgens. The pattern of PA1 ARir labeling
      was closely similar between animals and occurred in the lateral septum, medial
      preoptic area, bed nucleus of stria terminalis, anterior, cortical, accessory
      basal and medial amygdala, several hypothalamic nuclei including the supraoptic,
      anterior, paraventricular, ventromedial and arcuate nuclei, and the premammillary
      nucleus. No significant sex differences were observed. With the exception of the
      supraoptic nucleus, reported not to be labeled by autoradiography, earlier
      autoradiographic findings and the current immunocytochemical results, although
      not congruent, have noteworthy similarities.

PMID- 8547950
TI  - Evidence for short-loop feedback effects of ACTH on CRF and vasopressin
      expression in parvocellular neurosecretory neurons.
AB  - Immuno- and hybridization histochemical methods were used to examine a possible
      role for adrenocorticotropic hormone (ACTH) in regulating the expression of
      corticotropin-releasing peptides in rat hypothalamus. Densitometric assessments
      of relative levels of mRNAs encoding corticotropin releasing factor (CRF),
      arginine vasopressin (AVP) and oxytocin (OT) in the parvocellular division of the
      paraventricular nucleus (PVH) were carried out in intact, adrenalectomized (ADX)
      and hypophysectomized (HYPOX) animals. Both surgeries resulted in comparable
      increases in relative levels of CRF and AVP transcripts in the parvocellular PVH;
      no effects on OT mRNA in this compartment were evident. In a second experiment,
      ACTH or saline vehicle were administered systemically via osmotic minipump for
      seven days to rats submitted to both HYPOX and ADX surgeries. Lower replacement
      doses of ACTH reduced the number of detectable AVP-immunoreactive (AVP-ir) cells
      in the parvocellular PVH to 53% of that seen in vehicle-treated HYPOX/ADX
      controls; the number of CRF-IR cells was not significantly affected. Higher doses
      of ACTH resulted in counts of AVP- and CRF-IR neurons that were reduced to 32%
      and 70%, respectively, of control values. Staining patterns for the two peptides
      in the external lamina of the median eminence generally followed the cell count
      data. Neither densitometric nor combined immunohistochemical (for CRF-ir) and
      hybridization histochemical (for AVP mRNA) assays revealed any marked effect of
      ACTH on AVP mRNA expression in the parvocellular PVH of HYPOX/ADX rats. The
      results indicate that ACTH is capable of inhibiting corticotropin-releasing
      peptide, but not mRNA, expression in hypophysiotropic neurons. The mechanisms
      underlying these effects remain to be fully clarified.

PMID- 8547952
TI  - The role of inducible transcription factors in apoptotic nerve cell death.
AB  - Recent studies have shown that certain types of nerve cell death in the brain
      occur by an apoptotic mechanism. Researchers have demonstrated that moderate
      hypoxic-ischemic (HI) episodes and status epilepticus (SE) can cause DNA
      fragmentation as well as other morphological features of apoptosis in neurons
      destined to die, whereas more severe HI episodes lead to neuronal necrosis and
      infarction. Although somewhat controversial, some studies have demonstrated that
      protein synthesis inhibition prevents HI-and SE-induced nerve cell death in the
      brain, suggesting that apoptotic nerve cell death in the adult brain is de novo
      protein synthesis-dependent (i.e., programmed). The identity of the proteins
      involved in HI-and SE-induced apoptosis in the adult brain is unclear, although
      based upon studies in cell culture, a number of potential cell death and anti
      apoptosis genes have been identified. In addition, a number of studies have
      demonstrated that inducible transcription factors (ITFs) are expressed for
      prolonged periods in neurons undergoing apoptotic death following HI and SE.
      These results suggest that prolonged expression of ITFs (in particular c-jun) may
      form part of the biological cascade that induces apoptosis in adult neurons.
      These various studies are critically discussed and in particular the role of
      inducible transcription factors in neuronal apoptosis is evaluated.

PMID- 8547951
TI  - Neuropeptide Y and luteinizing hormone releasing hormone synergize to stimulate
      the development of cellular follicle-stimulating hormone in the hamster
      adenohypophysis.
AB  - Luteinizing hormone releasing hormone (LHRH) stimulates the development of
      cellular FSH immunoreactivity in the perinatal hamster adenohypophysis. Because
      neuropeptide Y (NPY) can act directly on rat adenohypophysial cells to stimulate
      FSH and LH release and potentiate the stimulatory effect of LHRH on FSH and LH
      release, we investigated the effects of NPY alone and in combination with a low,
      ineffective dose of LHRH on inducing cellular FSH immunoreactivity in the
      neonatal hamster adenohypophysis. Neonatal female pituitary glands were grafted
      beneath the right renal capsules of hypophysectomized-ovariectomized adult
      hamster hosts with a catheter implanted in the external jugular vein. After
      treatment, hosts were decapitated and graft tissue was stained for FSH and LH
      immunoreactivity. The mean percentage of adenohypophysial cells that stained for
      FSH was low (2.8%) in grafts in hosts infused continuously with heparinized
      saline vehicle for 7 days. In other hosts, peptides were pulsed through the
      catheter every 12 h for 7 days. The mean percentage of FSH cells also was low
      after pulsing 6 ng LHRH or 2 micrograms NPY but increased substantially when the
      two peptides were pulsed simultaneously. No differences in the mean percentage of
      LH cells existed between any of the groups. The results demonstrate that NPY and
      LHRH can synergize to induce cellular FSH immunoreactivity in the neonatal female
      hamster.

PMID- 8547953
TI  - Neurochemical and morphological changes associated with human epilepsy.
AB  - To date a multitude of studies into the morphology and neurochemistry of human
      epilepsy have been undertaken with variable, and often inconsistent, results.
      This review summarises these studies on a range of neurotransmitters,
      neuromodulators, neuropeptides and their receptors. In addition to this, novel
      changes in cell viability and sprouting have been identified and are discussed.
      Whether the alterations observed are a result of the seizures or are a
      contributory factor is unclear. However, it may be that following an initial
      insult (such as febrile convulsions, status epilepticus or head injury) secondary
      processes occur both of an anticonvulsant nature in an attempt to compensate for
      seizure activity, and in a kindling type of fashion, resulting in an increased
      susceptibility to seizures, leading to future seizures. Many of the alterations
      documented in this study probably represent one or both of these processes.
      Clearly no single chemical abnormality or morphological alteration is going to
      explain the clinically diverse disorder of epilepsy. However, by drawing together
      the neurochemistry and morphology of epilepsy, we may begin to understand the
      mechanisms involved in seizure disorders.

PMID- 8547954
TI  - Backpropagation of action potentials generated at ectopic axonal loci: hypothesis
      that axon terminals integrate local environmental signals.
AB  - This review deals with the fascinating complexity of presynaptic axon terminals
      that are characterized by a high degree of functional distinctiveness. In
      vertebrate and invertebrate neurons, all-or-none APs can take off not only from
      the axon hillock, but also from ectopic axonal loci including terminals.
      Invertebrate neurons display EAPs, for instance alternating with somatic APs,
      during survival functions. In vertebrate, EAPs have been recorded in the
      peripheral and central nervous systems in time relationship with physiological or
      pathological neuronal activities. In motor or sensory axon, EAP generation may be
      the cause of motor dysfunctioning or sensory perceptions and pain respectively.
      Locomotion is associated with rhythmic depolarizations of the presynaptic axonal
      membrane of primary afferents, which are ridden by robust EAP bursts. In central
      axons lying within an epileptic tissue EAP discharges, coinciding with paroxysmal
      ECoG waves, get longer as somatic discharges get shorter during seizure
      progression. Once invaded by an orthodromic burst, an ectopic axonal locus can
      display an EAP after discharge. Such loci can also fire during hyperpolarization
      or the postinhibitory excitatory period of the parent somata, but not during
      their tonic excitation. Neurons are thus endowed with electrophysiological
      intrinsic properties making possible the alternate discharges of somatic APs and
      EAPs. In invertebrate and vertebrate neurons, ectopic axonal loci fire while the
      parent somata stop firing, further suggesting that axon terminal networks are
      unique and individual functional entities. The functional importance of EAPs in
      the nervous systems is, however, not yet well understood. Ectopically generated
      axonal APs propagate backwards and forwards along the axon, thus acting as a
      retrograde and anterograde signal. In invertebrate neurons, somatically and
      ectopically generated APs cannot have the same effect on the postsynaptic
      membrane. As suggested by studies related to the dorsal root reflex, EAPs may not
      only be implied in the presynaptic modulation of transmitter release but also
      contribute significantly during their backpropagation to a powerful control
      (collision process) of incoming volleys. From experimental data related to
      epileptiform activities it is proposed that EAPs, once orthodromically conducted,
      might potentiate synapses, initiate, spread or maintain epileptic cellular
      processes. For instance, paroxysmal discharges of EAPs would exert, like a
      booster-driver, a powerful synchronizing synaptic drive upon a large number of
      excitatory and inhibitory postsynaptic neurons. We have proposed that, once
      backpropagated, EAPs are likewise capable of initiating (and anticipating)
      threshold and low-threshold somatodendritic depolarizations. Interestingly, an
      antidromic EAP can modulate the excitability of the parent soma.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8547956
TI  - Whither magic bullets and guided missiles: monoclonal antibodies 20 years later.

PMID- 8547955
TI  - The ratio of pre- to postganglionic neurons and related issues in the autonomic
      nervous system.
AB  - The motor outflow of the autonomic nervous system (ANS) is differentiated into
      two major divisions, parasympathetic (PSNS) and sympathetic (SNS). Both are
      organized hierarchically into pre- and postganglionic levels, but classically the
      two divisions have been assumed to differ in their ratios of pre- to
      postganglionic neurons. The PSNS been characterized as having lower ('one-to
      few') ratios, whereas the SNS has been described as possessing higher ('one-to
      many') ratios. These patterns have been assumed to measure differing divergences
      of the outflows. In this review, a ratio of pre- to postganglionic neurons is
      called a ratio index, and the idea that the PSNS and SNS have characteristically
      different ratio indexes and divergences is called the ratio rule. The putative
      differences in the ratio indexes of the two divisions - as well as Fulton's
      influential proposal that they form one of the bases of contrasting functional
      capacities of the PSNS and SNS - have been widely accepted for nearly for nearly
      three quarters of a century. A survey of the original observations yielding the
      concept of the ratio rule as well as the more recent estimates of pre- and
      postganglionic numbers, however, challenges both the generality and the adequacy
      of the ratio rule and indexes. The originally formulated differences between the
      PSNS and SNS represent an overgeneralization since they were based on
      observations of only two ganglia, the ciliary ganglion in the PSNS and the
      superior cervical ganglion in the SNS. Furthermore, these original estimates were
      based on limited samples and were subject to a number of counting artifacts. A
      survey of the literature suggests that ratio indexes vary much more within each
      ANS division than they do between the two divisions. When ganglia other than the
      ciliary and superior cervical are examined, the two divisions of the ANS have
      broad, largely overlapping ranges of ratio indexes. Additionally, other PSNS-SNS
      pairs can be found in which the relative sizes of their respective indexes are
      completely contrary to the ratio rule. For a given ganglion, there are
      substantial differences in the ratio index between species, between individuals
      of the same species, and between stages of development in the same species.
      Furthermore, both divisions of the ANS have wide and largely overlapping ranges
      of physiological effects varying from specific to diffuse, from local to
      widespread. Finally, the ratio index measure ignores the degree of convergence
      found in different ganglia, and it is insensitive to the fact that many ganglia
      have multiple functionally distinct motor neuron pools, each with separate inputs
      varying in their degrees of divergence and/or convergence. Thus ratio indexes do
      not differentiate the PSNS from the SNS, and conclusions based on such putative
      distinctions are questionable.

PMID- 8547957
TI  - Haplotype donor-generated graft-versus-leukemia responses: serendipity revisited.
AB  - This re-evaluation of a pilot study conducted nearly three decades ago (1965
      1970), in which serendipity played a central role in favorable responses of
      hematologic malignancies to the administration of adoptive lymphocytes from both
      parents, has been motivated by clearer understanding. Temporary remissions
      marking LAK cell-driven graft-versus-leukemia (GvL) responses were observed in
      four of seven acute leukemia patients associated with unique self-limited graft
      versus-host (GvH) reactions that were NK cell and cytokine related. Retinopathy
      not previously reported in a GvH setting was a consistent manifestation in these
      patients. Cure was achieved in an eighth patient with acute lymphoblastic
      leukemia after she had been given effective chemotherapy, an active role for the
      adoptive therapy indicated by the occurrence of a week of fever suggesting an
      abortive GvH reaction. Two of five patients with Hodgkin's disease also
      experienced favorable responses to parental leukocyte therapy, one exhibiting GvH
      manifestations almost identical to those seen in the acute leukemia patients when
      given the adoptive therapy successfully to spur recovery from severe herpes
      zoster that had interrupted curative radiation therapy. The GvH in the other
      patient was a more typical one, the key effect being an increase in circulating
      lymphocytes that may have contributed indirectly to cure with subsequent therapy.
      These and other attempts to apply GvL responses therapeutically, including those
      currently in favor, exemplify the shortcomings of partial mitogenic responses to
      alloactivation, which are dependent on engraftment, limited in scope, excessively
      toxic, and difficult to control. Treatment with mitogens such as PHA would be a
      superior alternative because of the abilities of these agents to regulate immune
      responses by simple modulations of dosage, scheduling, and modes of application.

PMID- 8547958
TI  - Long-term subcutaneous recombinant interleukin-2 as maintenance therapy:
      biological effects and clinical implications.
AB  - Several trials have evaluated the therapeutic efficacy of rIL-2 combined with
      more traditional treatments such as chemotherapy and radiotherapy, but the use of
      IL-2 as adjuvant therapy for minimal residual disease or to maintain clinical
      response obtained with other standard treatments has yet to be investigated. The
      aim of the present trial was to study the biological effects of maintenance long
      term treatment (6 months) with subcutaneous low-dose IL-2 in 16 patients with
      different neoplasms previously treated with chemo-immuno therapeutic regimens or
      with surgery (7 metastatic renal cancers, 5 locally advanced renal cancers
      previously subjected to radical nephrectomy, 2 metastatic breast cancers, 1 small
      cell lung cancer, and 1 metastatic melanoma). Clinical tolerability, feasibility
      and therapeutic implications are also discussed. The IL-2 schedule was as
      follows: 4.5 million IU/day, 3 times weekly for 6 months. A total of 14 patients
      completed therapy without requiring dose modifications and are free of
      progression after a median duration of 8+ months (range: 7+ to 34+) while two
      patients progressed during therapy (one inflammatory breast cancer and one renal
      cancer). Important and persistent hemato-immunostimulating effects in both
      soluble (IL-2, sIL-2R, IL-6) and cellular (lymphocyte subsets, monocytes,
      eosinophils) parameters were noted during the entire treatment. The IL-2 related
      toxicity was quite low. Moreover, this long-term IL-2 therapy could control
      neoplastic growth and thus prolong clinical response obtained with standard
      treatments. Prospective randomized studies regarding the clinical efficacy have
      been initiated.

PMID- 8547959
TI  - Evaluation of low dose alpha-interferon (Roferon-A) in patients with advanced
      renal cell carcinoma: a Southwest Oncology Group study.
AB  - Alpha-interferon (IFN) has been shown to produce antitumor responses among
      patients with advanced renal cell carcinoma. While responses have been observed
      over a range of IFN doses and schedules, significant toxicities can be
      experienced from relatively high doses given three to five times weekly. Based
      upon the report of a pilot study indicating that low dose daily IFN could produce
      antitumor responses with minimal toxicity, the Southwest Oncology Group
      investigated this schema in a phase II trial. Patients with bidimensionally
      measurable disease were treated with Roferon-A 1 million units subcutaneously
      daily and tumor assessments were conducted on a monthly basis. There were no dose
      escalations and no dose reductions for toxicity. The treatment was well tolerated
      with only two patients withdrawing from treatment because of side effects. Among
      56 eligible patients treated, there were five partial responses and one complete
      response for an overall response rate of 11% (95% confidence interval, 4 - 22%).
      However, objective antitumor responses could not be determined for 16 of the 56
      patients. Among the 40 fully evaluable patients the 6 objective responses yields
      a response rate of 15% (95% confidence interval, 5.7-30%). It is concluded that
      this dose and schedule of IFN has activity against advanced renal cell carcinoma.
      A randomized trial would be required to determine if this low dose regimen is as
      effective as the higher doses which have been used traditionally.

PMID- 8547960
TI  - In vitro cell-mediated immune responses induced by a polyvalent allogeneic
      melanoma vaccine.
AB  - Peripheral mononuclear cells (PMNC) from 18 melanoma were monitored for vaccine
      related changes in their immune responses by measuring functional activity and
      phenotypic expression of PMNC prior to- and following 4-6 vaccinations. Assays
      included: cytolytic responses directed against melanoma cell lines included in
      the vaccine (M20, M14, HM54 and SKMel28), control melanoma (SKMel23) and non
      melanoma (SKCo1, K562 and Daudi) cell lines. Direct lytic responses were
      significantly enhanced following vaccine treatment, mainly against M20 cell line
      and was further augmented following In Vitro Stimulation (IVS) by Mit-C-treated
      M20 or M14 cells. No evidence was found of augmentation of NK or LAK activity by
      vaccine treatment. Significantly enhanced proliferative responses to of vaccine
      treated patients' PMNC to melanoma cell lines were also observed. The human
      melanoma cell lines used for vaccine preparation (M14, M20 and SKMel28) are high
      expressors of HLA class I, while high expression of HLA-DR only on M20 cells.
      Cell surface markers' study indicate a shift in CD4/CD8 ratio from 1.1 to 2.1 and
      increase in CD25 and HLA-DR positive cells. In M20-stimulated cultures of post
      vaccine patients' PMNC the predominant phenotype was CD3+/CD4+. In conclusion, we
      have demonstrated that treatment with polyvalent allogeneic melanoma vaccine
      significantly augments T-cell mediated CD3+/CD4+), anti-melanoma lytic and
      proliferative responses, non-MHC-restricted.

PMID- 8547961
TI  - Phase I study of tumor necrosis factor plus actinomycin D in patients with
      androgen-independent prostate cancer.
AB  - Based on preclinical studies which reveal enhanced antitumor activity of tumor
      necrosis factor (TNF) when combined with actinomycin D in human prostate cancer
      cell lines, we performed a phase I clinical study combining TNF and actinomycin
      D. All patients had metastatic prostatic carcinoma exhibiting androgen
      independent growth. Patients were treated with a combination of a short infusion
      of actinomycin D followed by a TNF infusion daily for five consecutive days.
      Soluble TNF receptor p60 was not modulated by treatment but p80 receptor
      increased significantly following treatment with a combination of TNF and
      actinomycin D (baseline median 3.4 ng/ml) range 2.5-6.6 ng/ml follow up (9.3
      ng/ml) range 6-24 ng/ml. We concluded that the maximum tolerated dose of
      continuous infusion TNF and short infusion actinomycin D is 400 micrograms/m2 of
      actinomycin D and 400 micrograms/m2 of TNF. The increased soluble receptor
      isoform (p80) may account for the lack of clinical activity seen in this trial.
      Should these results be confirmed, a strategy focused on overcoming the
      upregulation of the TNF soluble receptor will be required before further study of
      TNF should be considered.

PMID- 8547962
TI  - Rhabdoid tumor of the kidney in an adult: review of the literature and report of
      a case responding to interleukin-2.
AB  - Rhabdoid tumor of the kidney is an uncommon and highly aggressive malignancy
      usually found in the pediatric age group. This tumor does not respond well to
      aggressive chemotherapy regimens and survival tends to be short. Only two cases
      of rhabdoid tumor of the kidney occurring in adults have been described
      previously. The third case of a rhabdoid tumor of the kidney in an adult is
      presented here. This clinical case report is unique not only because of the rare
      occurrence of this tumor in adulthood but because the patient described had an
      objective antitumor response to outpatient low dose interleukin-2. This single
      case report may have therapeutic implications for other patients with this tumor.

PMID- 8547963
TI  - Selenium (Se) cytotoxicity in drug sensitive and drug resistant murine tumour.
AB  - Selenium is known to inhibit growth rate of neoplastic cells. We have
      investigated the role of selenium (Se) in resensitization of the adriamycin (ADR)
      resistant murine P388/ADR cells to the action of ADR. The experiments were
      performed in the ADR sensitive parental P388 murine leukemia (P388/S) and its
      subline P388/ADR, resistant to ADR, developed in our laboratory. The effect of Se
      was observed to be dose dependent i.e. Se at a concentration of 5 x 10(-8)M
      resulted in potentiation of DNA biosynthesis whereas 5 x 10(-6)M and 5 x 10(-5)M
      Se resulted in inhibition of DNA-biosynthesis in P388/S cells. Along with ADR
      there was a further increase in inhibition of DNA biosynthesis. In P388/ADR
      cells, Se at 5 x 10(-6)M and 5 x 10(-8)M concentration resulted in inhibition of
      DNA biosynthesis, which increased further when combined with ADR indicating
      resensitization of these cells to the action of ADR. The inhibition was observed
      to be partially irreversible. These results were further confirmed in the in vivo
      and in vitro bioassays where the Se and Se+ ADR treatments resulted in increased
      lifespan of tumor bearing mice.

PMID- 8547964
TI  - Situated clinical cognition.
AB  - The features characterizing study of clinical cognition in situ are formulated
      as: Re-cognition of context, culture, history and affect. Socializing and
      phenomenalistic elements are again included in the research agenda. Interest for
      representations: an analysis level is reserved for the symbols, rules and images
      relevant to define in models of clinical cognition. De-emphasis on computer
      modeling: investigations focus on the 'functional systems' in which computers are
      involved. Rootedness in classical philosophical problems: issues concerning
      situated clinical cognition are connected to the width of available theoretical
      literature. Belief in interdisciplinary studies: productive interactions between
      the new and traditional disciplines is anticipated, implying that new shared
      methods have to be developed. When scientific perspectives are broadened, a new
      balance has to be found between the relevance of the subject of study and
      methodological rigor. The situated clinical cognition framework is to allow for
      moving between models, theories, and perspectives, as it does not presuppose a
      singular model of clinical thinking.

PMID- 8547965
TI  - Objects, contradictions and collaboration in medical cognition: an activity
      theoretical perspective.
AB  - Activity theory suggests three principles for contextual analysis of clinical
      cognition: orientation to objects in cognition, role of contradictions in
      cognition, and the importance of collaboration in cognition. Focusing on the
      objects of cognition calls attention to differences across medical work settings.
      There is an interconnection between the type of the object encountered, the
      physician's generalized conception of the object, and the physician's choice of
      linearization or lateralization as cognitive strategy. In a consultation the
      object of medical cognition is locally constructed through a series of mediated
      actions. Identification of contradictions at the level of the institutional
      activity system is crucial for the understanding of failures and innovations in
      actions of medical cognition. A conceptual model for analyzing such
      contradictions is presented. It is demonstrated that medical cognition is a
      collaborative achievement between the physician and the patient. Patients use a
      variety of strategies to turn their experienced health problems into manageable
      problems. The patient's strategy can and often does influence the physician's
      strategy and the outcome of the consultation.

PMID- 8547967
TI  - Objectification and negotiation in interpreting clinical images: implications for
      computer-based patient records.
AB  - This paper concerns the role of images and visualization in clinical practice and
      decision making. In particular, how physicians talk about and use images are
      discussed. Findings from evaluation studies of clinical imaging computer
      information systems suggest that the role and interpretation of images is
      negotiated, an example of how what is seen is influenced by the practice
      community, and, therefore is situated in specific instances of clinical decision
      making. An understanding of professional vision with respect to how physicians
      use and think about images may aid in developing clinical imaging systems,
      computer-based patient records, and other clinical information systems that could
      integrate well with clinical work practice.

PMID- 8547966
TI  - Steering through the murky waters of a scientific conflict: situated and symbolic
      models of clinical cognition.
AB  - The situated action perspective, which embraces a diversity of views, challenges
      several of the fundamental assumptions of the symbolic information-processing
      framework underlying cognitive science and artificial intelligence. In this
      paper, we consider the following issues; symbolic representations, plans and
      actions, distributed cognition, and the transfer of learning. We evaluate each of
      these issues in terms of research and theories in clinical cognition and examine
      the implications for education and training, and for the integration of
      intelligent systems in medical practice. We argue for a reconceptualization of
      the symbolic framework in terms of the way the role of internal representations
      and cognitive activities are perceived. However, symbolic representations are
      integral to medical cognition and should continue to be central in any
      theoretical framework. A re-examination of cognitive science in medicine in terms
      of the relationship among physicians, technology, and the workplace could prove
      to be constructive in bridging the gap between theory and practice.

PMID- 8547968
TI  - A theoretical approach to artificial intelligence systems in medicine.
AB  - The various theoretical models of disease, the nosology which is accepted by the
      medical community and the prevalent logic of diagnosis determine both the medical
      approach as well as the development of the relevant technology including the
      structure and function of the A.I. systems involved. A.I. systems in medicine, in
      addition to the specific parameters which enable them to reach a diagnostic
      and/or therapeutic proposal, entail implicitly theoretical assumptions and socio
      cultural attitudes which prejudice the orientation and the final outcome of the
      procedure. The various models -causal, probabilistic, case-based etc. -are
      critically examined and their ethical and methodological limitations are brought
      to light. The lack of a self-consistent theoretical framework in medicine, the
      multi-faceted character of the human organism as well as the non-explicit nature
      of the theoretical assumptions involved in A.I. systems restrict them to the role
      of decision supporting "instruments" rather than regarding them as decision
      making "devices". This supporting role and, especially, the important function
      which A.I. systems should have in the structure, the methods and the content of
      medical education underscore the need of further research in the theoretical
      aspects and the actual development of such systems.

PMID- 8547969
TI  - A revised strategy for HIV and AIDS health promotion.

PMID- 8547970
TI  - [Inducing feminization in Turner syndrome].

PMID- 8547972
TI  - [Ambulatory 24-hour home pH-metry: parental and familial reactions. Prospective
      study of 100 cases].
AB  - BACKGROUND: The ambulatory twenty-four hour esophageal pHmetry is nowadays a
      common mode of assessment of gastro-esophageal reflux in children. The aim of
      this study was to evaluate the impact of the test on child and family's ordinary
      daily life. MATERIAL AND METHODS: One-hundred children (64 boys, 36 girls) were
      included in this study during a 10-month period from August 1992 until May 1993.
      Mean age was 2 years 9 months (range: 22 days--12 years). Forms with a list of
      questions concerning parental understanding of the test, child's reaction after
      introduction of the pH-electrode, general reactions in the household, and
      eventual disturbance of the child's temper and appetite, were given to the
      parents. Six months later, 81 families were contacted by telephone and asked the
      same questions. Children were divided into three groups: those under 1 year of
      age (n = 38), from 1 to 4 years (n = 35), and more than 4 years (n = 27).
      RESULTS: One child aged 2 months had to be admitted to hospital due to the
      mother's overanxiety. The majority of parents (80%) assumed they knew about the
      principles of the test, with little change once the test was over. Those whose
      child had previously been submitted to the test were less apprehensive. When the
      test was first initiated, 81% of parents feared it would cause some discomfort,
      either due to pain (69%), or to poor acceptance at home (25%) with the risk of
      having the catheter accidently removed. Once the catheter had been positioned
      with the parents close to the child at that time, its presence was judged by them
      tolerable in 88.9% of cases. Once at home, 84.8% of the parents were not worried,
      as the child was calm (83.8%) and also due to the possibility for them to get in
      touch with the physician if necessary (86.9%). No change in routine daily life
      was reported by 80.8% of the families; in only 19.2% was the child reported to be
      overwhelmed with the test. When asked if the test should be undertaken another
      time, 91.9% would still prefer it as a home procedure, the only families
      requesting it be done in hospital being those with a history of sudden death
      syndrome. CONCLUSION: pHmetry test as a 24-hour procedure done at home may be the
      source of some discomfort and anxiety both to the child and parents; yet it
      appears to be generally well-accepted, both for its non-aggressive and diagnostic
      value.

PMID- 8547971
TI  - [Use of EMLA cream in premature and full-term newborn infants. Study of efficacy
      and tolerance].
AB  - BACKGROUND: Mild methemoglobinemia is a known side-effect of one of the
      constituents of EMLA cream, this topical local anesthetic is used with great
      caution in neonates. POPULATION AND METHODS: One hundred and sixteen neonates
      admitted from January to July 1994 in an intensive care unit were included in the
      study. All required skin punctures which were performed 1 h 30-2 hours after EMLA
      had been applied on the skin. A reaction score (0 to 5) to skin puncture was
      established 157 times (120 after and 37 without local anesthesia); methemoglobin
      (Met Hb) concentrations were measured in 47 blood samples, 18-24 hours (40.4% of
      samples) or 2-3 days (36.2%) after application of EMLA. RESULTS: Ninety-four
      neonates were quiet before puncture (score 0-1). Among them, 57% of those who
      were given EMLA had a low score (2 or less) vs 18% without EMLA. A low reaction
      was observed in 65% when the dressings had been kept in place for at least 90
      minutes vs 15% with a shorter application. A lower reaction was noted in 78.8% of
      cases after venopuncture (41% after arterial puncture). No Met Hb level was above
      5% and 7 (15%), in five neonates, were between 3 and 5%. There was no clear
      relationship between methemoglobinemia and gestational age or duration of
      dressing. CONCLUSION: EMLA cream is effective and safe in neonates including
      preterms, when it is applied in a small amount once a day.

PMID- 8547973
TI  - [Re-education in biofeedback: role in terminal constipation in children].
AB  - BACKGROUND: Chronic constipation with or without encopresis is often associated
      with abnormal defecation dynamics evidenced by manometric study and possibly
      manageable with biofeedback treatment. PATIENTS AND METHODS: Twenty-six children
      more than 5 years of age suffering from constipation with or without encopresis
      for at least 6 months were treated with biofeedback plus lactulose; 15 of them
      were also given psychiatric attention. Pressure recordings from the internal and
      external sphincters in response to transient balloon distension of the rectum
      were obtained in all patients as did the recto-anal inhibitory reflex and the
      rectal sensitivity. RESULTS: Sixteen patients were considered as definitely cured
      or improved with this management; two others had relapses 6-12 months later and
      five were not improved; the three remaining patients were lost for follow-up.
      CONCLUSION: As already reported, biofeedback treatment represents an interesting
      role in management of such children.

PMID- 8547974
TI  - [Neonatal acute leukemia: apropos of 7 cases].
AB  - BACKGROUND: Acute leukemia in neonates is rare and is more severe than leukemia
      in childhood. POPULATION: Seven cases (four girls, three boys) were included in
      this series. Leukemia was diagnosed at birth in three cases; hepatosplenomegaly
      was seen in five cases and skin nodules in three. Hyperleukocytosis more than
      100,000/mm3 was present in four cases; the WBC and differential counts were
      normal in two. A meningeal involvement was seen in one case. The leukemia was
      lymphoblastic (ALL) in three cases and myeloblastic (AML) in four. Intensive
      chemotherapy induced complete remission in five patients, persisting 5 and 4
      years after the diagnosis in two. Classic risk factors such as high white blood
      counts, central nervous system involvement, myeloblastic lineage, absence of
      CALLA (common acute lymphoblastic leukemia antigen) expression and abnormal blast
      cell karyotype interesting the 11q23 area were found again in this series. Risk
      related to drug toxicities and infectious complications were also noted in this
      series of very young patients. CONCLUSIONS: The outcome may depend on progress in
      pharmacology, search for new drugs and use of bone marrow transplantation.

PMID- 8547975
TI  - [Spontaneous colonic perforations revealing Ehlers-Danlos syndrome type IV].
AB  - BACKGROUND: The malignant form of Ehlers-Danlos syndrome type IV owes its bad
      reputation to a proneness to spontaneous rupture of bowel or large vessels, which
      may reveal the disease. CASE REPORT: A girl suffered acute rupture of the sigmoid
      at the age of 5 years and rupture of the left colon, twice, at the age of 11 and
      13 years, respectively. These ruptures required colostomy and finally colectomy.
      A proneness to bruisability, history of dislocation of hips, hypermobile joints,
      ovarian cysts and some minor abnormalities of her face resembled that of the
      Ehlers-Danlos syndrome which was confirmed by optic and electronic microscopy of
      the skin biopsy. CONCLUSION: This is the youngest case of rupture of bowel
      reported in Ehlers-Danlos syndrome. Long-term prognosis is influenced by
      repetition of intestinal ruptures and occurrence of vascular complications.

PMID- 8547976
TI  - [Effects of hypocaloric diet on respiratory manifestations in Willi-Prader
      syndrome].
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a multisystem disorder with
      hyperphagia and obesity. Breathing disorders such as snoring, sleep apnea
      syndrome, and sleep hypoventilation have also been reported. CASE REPORT:
      Jonathan was born with the typical features of PWS. He developed exercise
      dyspnea, cyanosis and nocturnal sweating at the age of 3 years. A few months
      later, a respiratory failure required his admission to the intensive care unit.
      His weight was then 48 kg (300% ideal body weight (IBW); physical examination
      showed polypnea (60 breaths/min), cyanosis, fat deposition on the chest wall.
      Transcutaneous oxygen saturation was 65%, carbon dioxide tension 81 mmHg
      (capillary sample). Pulmonary hypertension was found (mean arterial pulmonary
      pressure = 55 mmHg). Polysomnography detected hypoventilation with persistent
      hypoxemia increasing during the night and transient dips of oxygen saturation
      with bradycardia. He was treated with oxygen, mechanical ventilation (facial
      mask) and a low caloric diet (600 cal/day). Four months later, he weighed 33 kg
      (200% IBW); the respiratory features had resolved and gazometric values and
      pulmonary pressure returned to the normal ranges. Polysomnography showed only
      obstruction apnea and hypopnea without oxygen desaturation. CONCLUSIONS: Patients
      with PWS may develop respiratory symptoms sufficient by severity to be life
      threatening. They are related to morbid obesity and are influenced by a
      hypocaloric diet. Follow-up of patients with this syndrome must include repeated
      respiratory evaluation.

PMID- 8547977
TI  - [A rare cause of severe diarrhea in children: pseudomembranous colitis].
AB  - BACKGROUND: Pseudomembranous colitis is a rare and serious complication of
      treatment by antibiotics. The case of a patient with a protracted
      pseudomembranous colitis followed by two relapses is reported. CASE REPORT: A 4
      year-old boy was admitted after 18 days of profuse and feverish diarrhea. He had
      been given amoxycillin for 10 days, one and a half months previously. His
      temperature was 40 degrees C; he had abdominal pain and leucocytosis was
      30,000/mm3. The situation rapidly improved with digestive rest and i.v.
      antibiotic therapy. Relapse of diarrhea together with bilious vomiting and acute
      abdominal pains required readmission three days after his discharge. Search for
      Clostridium difficile in stools remained negative. The diagnosis of
      pseudomembranous colitis was confirmed by sigmoidoscopy and intestinal biopsy.
      The patient was given parenteral nutrition for 3 weeks and vancomycin. The
      disease was complicated by anasarca related to severe protein-loosing enteropathy
      but evolution was finally favourable after a two month period. CONCLUSION:
      Pseudomembranous colitis remains a serious affection in childhood; its prognosis
      largely depends on the precocity of diagnosis and treatment.

PMID- 8547978
TI  - [Anticardiolipin antibodies, cerebral ischemia and adrenal hemorrhage in a
      newborn infant].
AB  - BACKGROUND: Anticardiolipin antibodies, usually associated with vascular
      thrombosis in systemic lupus erythematosus, have been recently found associated
      with strokes in childhood, and acute adrenal hemorrhage in the adult. CASE
      REPORT: A 3 day-old fullterm newborn suffering from cerebrovascular ischemia and
      bilateral massive hemorrhage was found to have anticardiolipin antibodies
      detected during the neonatal period and 7 months later. There was no evidence of
      pathology in the mother or perinatal asphyxia. However, anticardiolipin
      antibodies were present in the mother 5 and 15 weeks after delivery. CONCLUSION:
      Association of anticardiolipin antibodies and vascular thrombosis has never been
      reported in the neonate. Persistence of such antibodies favor the hypothesis that
      they are not transmitted by the mother; they could represent an early
      manifestation of primary antiphospholipid syndrome.

PMID- 8547979
TI  - [Sedation and analgesia in children].
AB  - This article describes the most current and effective means for providing
      sedation and analgesia for the pediatric patient. Three basic levels for sedation
      can be defined: conscious sedation, deep sedation and general anesthesia.
      Treatment of pain is also established according to an analgesic ladder. Providing
      safe and effective sedation and analgesia to children requires appropriate
      selection of drugs and dosage, proper monitoring, knowledge of potential side
      effects, and adequate airway management equipment and personnel. Agents available
      for sedation and analgesia of children and therapeutic options according to
      different clinical situations are described.

PMID- 8547980
TI  - [Pain in hospitalized children].
AB  - Pain is present in many hospitalized children and this requires from every
      physician a constant attention to its recognition, evaluation and treatment. The
      semeiology of pain differs whether it is acute or chronic. Acute pain can be
      recognized from its various behavioural, motor and neurovegetative
      manifestations. Pain evaluation must be adapted according to age: autoevaluation
      procedures for children older than 5 years, behavioural scales for children
      younger than 5 years. One must know that there is an appropriate and efficient
      treatment for each stage of pain intensity. For a better recognition and
      management of pain in hospitalized children, the organization of teams
      specialized in the evaluation and treatment of pain in children is to be
      encouraged.

PMID- 8547981
TI  - [Cardiovascular evaluation in athletic children].
AB  - Although rare, sports related sudden cardiac deaths in children and adolescents
      justify the search for risk factors in any child or adolescent who wishes to
      practice sports. Each time that history and careful clinical cardiovascular
      examination point to a possible cardiovascular abnormality, an electrocardiogram
      and an echocardiography must be performed. Exercise testing is useful to
      appreciate the cardiovascular tolerance, either in normal subjects or in subjects
      with a cardiovascular abnormality; its interpretation requires good knowledge and
      understanding of hemodynamic responses to exercise. Indications, risks and
      procedures of exercise testing are discussed with reference to exercise
      physiology.

PMID- 8547983
TI  - [Imaging of acute pyelonephritis].

PMID- 8547982
TI  - [Radiological case of the month. Esophageal atresia and congenital esophageal
      stenosis].

PMID- 8547984
TI  - [Camphor poisoning: repeatedly?].

PMID- 8547985
TI  - [Acute morbilliform aseptic meningitis: diagnostic contribution of the viral
      genome research by RT-PCR].

PMID- 8547986
TI  - [Ulcers of the small intestine 12 years after ileo-sigmoid anastomosis for
      neonatal necrotizing enterocolitis].

PMID- 8547987
TI  - [G6PD deficiency and acute poisoning by anti-mite mothballs].

PMID- 8547988
TI  - [Recurrence of typhoid fever in an adolescent treated with ceftriaxone].

PMID- 8547989
TI  - [Results of the world-wide prevalence of infantile obesity. What are the
      perspectives?].

PMID- 8547990
TI  - [Skin reactions following administration of sulfonamide].

PMID- 8547991
TI  - [Pediatric psychiatric emergencies in a hospital for children].

PMID- 8547992
TI  - [Isolated bilateral dysplasia of the hip in children].
AB  - BACKGROUND: Dysplasia epiphysealis capitis femoris is not well-known despite its
      relative frequency; its prognosis is difficult to predict. POPULATION AND
      METHODS: Twenty children (19 boys and one girl) aged 2.5 to 7 years at diagnosis
      were included in the study. They had delayed capitis femoris apparition, or a
      fragmentation of dysplastic capitis femoris. The prognosis remained poor in 13
      patients. DISCUSSION: Most authors consider that prognosis of this disease is
      always favorable. We failed to find early prognostic criteria; radiological
      findings valuable for prognosis are only present after 3 to 6 years. CONCLUSION:
      Early new imaging techniques have to be evaluated before considering
      impossibility to foresee the evolution.

PMID- 8547993
TI  - [Localized granuloma annulare in children: outcome in 30 cases].
AB  - BACKGROUND: The outcome of granuloma annulare in childhood is not well defined.
      POPULATION AND METHODS: A questionnaire was sent to the family of 40 children
      under 15 years of age examined for granuloma annulare from 1987 to 1992. Thirty
      of them answered, permitting a retrospective study. RESULTS: The sex-ratio F:M
      was 1.3:1. Ages ranged from 1 to 13 years (mean: 4.5 years). Lesions developed
      before the age of 5 years in 76.7% of cases. Involved sites were essentially the
      back of hands and feet; lesions were unique in half of the cases. No association
      with diabetes mellitus was found. Three familial cases were observed. Duration of
      lesions varied from 6 months to 7 years (mean: 2.5 years). Age at onset, sex,
      biopsy and treatment had no influence on outcome. CONCLUSION: Granuloma annulare
      in children is a benign disorder but its course may last up to several years.

PMID- 8547994
TI  - [Percutaneous occlusion of patent ductus arteriosus by the Rashkind double
      umbrella device].
AB  - BACKGROUND: The transcatheter option consisting of implanting and releasing an
      occlusive device designed as a double-umbrella is an interesting alternative to
      surgery aimed to close persistently patent ductus arteriosus. POPULATION AND
      METHODS: Closure of a duct with the Rashkind device had been planned in 113
      children. The procedure was abandoned in 12 with inadequately sized ducts (too
      large or too small). This study therefore included 101 attempts in patients aged
      2.3 months to 18.5 years (m +/- 1 SD = 45.9 +/- 43.2 months) whose weights ranged
      from 3.3 to 87 kg (m +/- 1 SD = 15.7 +/- 11.7 kg). The narrowest dimension of the
      duct on the aortograms ranged from 1.2 to 6.2 mm (m +/- 1 SD = 2.9 +/- 0.9 mm).
      RESULTS: The procedure failed in seven patients because of a too large and/or
      tubular vessel, causing removal of the device prior to release in five patients,
      or surgical extraction after it had embolized into a pulmonary artery branch in
      two patients. An early acute hemolysis requiring again the surgical removal of an
      instable device in a tubular duct was seen in one case. Two patients had femoral
      artery occlusion successfully treated with thrombolytic agents. Complete
      occlusion was immediately proven in 32 (35%) of the 92 successful and stable
      implantations. These figures raised to 64% (59 cases) prior to discharge. At
      final follow-up (0.3-59 months, m +/- 1 SD = 13.8 +/- 14.4 months), another 16
      total occlusions were observed and one patient was successfully managed by a
      second implantation. The final occlusion rate was 83% (76 cases). Of the 16
      residual shunts, five were surgically suppressed and the remaining were minimal.
      CONCLUSION: Transcatheter occlusion of the patent ductus arteriosus is safe in
      children weighing more than 5 kg, having ducts with a narrowing ranging from 1 to
      6 mm. It is efficient in five out of six cases and has less disadvantages than
      surgery.

PMID- 8547995
TI  - [Neurologic development in premature infants under 33 weeks of gestational age:
      determination of risk of neurological abnormalities in a prospective regional
      survey with a control group].
AB  - AIM: The purpose of this population-based study was to compare the incidence of
      neurodevelopmental disability and its risk factors between preterm and full-term
      infants matched as control group. POPULATION AND METHODS: The preterm cohort
      included 203 infants born between 25 and 33 weeks of gestational age in the
      region of Franche-Comte (France) during a two-year-period. The control group
      included 196 full-term infants born in the same maternities. Survival up to the
      date of follow-up was 171/203 (84%) for preterms and 195/196 (99.5%) for full
      term infants (uncorrected age, mean 12 months). Neurodevelopmental assessments
      were performed by pediatricians or physicians on 164/171 surviving preterms (96%
      follow-up) and 179/195 full-terms (92%). RESULTS: Thirty-two (19.5%) preterm
      infants had disability, ten of these (6%) showing severe disability. Five (2.8%)
      full-term infants had disability, one of these (.5%) having severe disability.
      Risk factors predicting a disability included in a multivariate approach:
      prematurity (odds-ratio [OR]: 7.8), maternal age > 37 (OR: 3.0), lack of
      profession for both parents (OR: 3.7), male gender (OR: 2.9). The pediatrician
      observed a disability more frequently than the physician (OR: 2.46). Likewise,
      risk factors predicting a severe disability included: prematurity (OR: 10.8),
      lack of profession for both parents (OR: 5.8) and monochorial twin-placentation
      (OR: 4.5). CONCLUSIONS: Prematurity is not the only risk factor to be taken into
      account for neurodevelopmental evaluation of premature infants, but its influence
      still remains widely predominant.

PMID- 8547996
TI  - [Congenital adrenal hyperplasia and testicular hypertrophy].
AB  - BACKGROUND: Testicular tumors have been reported in boys and adolescents with
      congenital adrenal hyperplasia (CAH) inadequately controlled by hormonal therapy.
      CASE REPORTS: Two adolescents were treated for CAH due to 21-hydroxylase
      deficiency. They developed hyperplastic nodular testes at the age of 16 and 17
      years, respectively. CAH in both was inadequately controlled as confirmed by
      hormonal studies. The tumors regressed after adequate steroid therapy in the
      first patient but persisted in the second patient despite normalization of 17-OH
      progesterone and plasma renin activity. CONCLUSION: Testicular ultrasonography
      should be systematic in all male patients with CAH since radiological findings
      are earlier than clinical manifestations. The ACTH-dependent tumors require
      intensification of hormonal therapy in order to obtain tumoral regression and to
      prevent infertility.

PMID- 8547997
TI  - [Hypoplasia of abdominal aorta, rare cause of hypertension in childhood].
AB  - BACKGROUND: The majority of children with secondary hypertension have a renal
      abnormality or renovascular lesions. Coarctation of the aorta is also a classical
      cause, rarely located to the abdominal aorta. CASE REPORTS: Two girls, 11 and 12
      years-old, were suspected of having recent sustained hypertension. Pulsed-wave
      doppler ultrasonography and angiography showed abdominal aortic hypoplasia
      associated with renal artery stenosis, unilateral in one patient and bilateral in
      the other. Both patients became normotensive 10 and 18 months, respectively,
      after corrective vascular surgery. CONCLUSION: Examination of the abdominal part
      of the aorta is mandatory in all patients with hypertension.

PMID- 8547998
TI  - [Perinatal spinal cord injuries].
AB  - BACKGROUND: Injury to the spinal cord is still observed in the neonate. Its
      prognosis is poor. CASE REPORTS: The first neonate was delivered by cesarean
      section for breech presentation with hyperextension of the neck. She rapidly
      developed acute respiratory distress and paraplegia. MRI showed spinal cord
      hemorrhage involving the cervical and upper thoracic cord with rupture of the
      cord. The patient died a few weeks later. The second neonate was delivered
      vaginally in breech presentation without any difficulty. She progressively
      developed tetraplegia evolving into spasticity. MRI showed stretching of cervical
      spinal cord. The patient later developed sphincter disturbances, repeated urinary
      and pulmonary infection and severe scoliosis. CONCLUSIONS: Early prenatal damage
      to the spinal cord was possible in the first patient. Ultrasonography could help
      to evaluate the extent of damage. The condition leads to difficult ethical and
      therapeutic problems.

PMID- 8548000
TI  - [Role of macrolides in the treatment of respiratory tract infections in
      children].
AB  - Macrolides are antibiotics with high intracellular concentrations. They have a
      bacteriostatic activity but are also bactericides for concentrations five times
      greater than the minimal inhibitory concentration, concentrations in which they
      reach in the respiratory tract. They are usually active on Streptococcus,
      Neisseria, Moraxella catarrhalis, Listeria monocytogenes, Bordetella pertussis,
      Pasteurella multocida, Chlamydia, Mycoplasma pneumoniae, Legionella pneumophila
      and Helicobacter pylori. They have few secondary effects, some in relation with
      drug interactions. Their main indications are bronchopulmonary infections due to
      Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis and Legionella
      pneumophila. They are also useful in whooping cough allowing the eradication of
      Bordetella pertussis in the rhinopharynx, thus limiting the dissemination of the
      infection in children. In amygdalitis and pharyngitis, macrolides are a good
      substitute in the case of allergy to penicillin. New generation of macrolides
      (roxithromycine, clarithromycine, dirithromycine, azithromycine) might open other
      interesting therapeutic perspectives.

PMID- 8547999
TI  - [Spontaneous umbilical cord hematoma, a rare cause of acute fetal distress].
AB  - BACKGROUND: Spontaneous umbilical cord hematoma is a rare life-threatening
      gestational accident. CASE REPORT: A 26 year-old primipara was examined at 38
      weeks of gestation for fetal monitoring. There were a number of fetal
      decelerations with loss of baseline variability. Cesarean section performed for
      acute fetal distress resulted in a male infant with an Apgar score of 3 at 1
      minute and 7 at 5 minutes and neonatal anemia (Hb: 11.6 g/l). Four umbilical cord
      hematomas were observed. Microscopic examination revealed a ruptured umbilical
      vein without other abnormality. Post natal evolution was marked by hypoxic
      ischemic encephalopathy and death. CONCLUSION: Spontaneous umbilical cord
      hematoma is rare (1/5,500 births) and often due to rupture of the umbilical vein.
      Risk factors are shortness or traction of the cord, post-maturity and infection.
      Umbilical cord hematomas are usually responsible for severe fetal distress or
      death.

PMID- 8548001
TI  - [Cerebral hypoxic and ischemic damage in newborn infants: cellular mechanisms and
      role of excitatory amino acids].
AB  - Brain damage from hypoxia-ischemia plays a major role in neonatal mortality and
      morbidity. Different lesional mechanisms have been proposed. The most recent
      hypothesis involves the excitatory amino acids, especially glutamate. In this
      review, arguments in favour of a glutamate involvement in the lesional process
      are presented, with particular attention to the consequences of glutamate
      fixation on post synaptic receptors, especially N-methyl-D-aspartate receptors.
      Alterations of the intracellular concentration of calcium may also play a role in
      the pathogenesis of hypoxic-ischemic lesions. A better understanding of the
      metabolic processes could lead to new therapeutic possibilities.

PMID- 8548002
TI  - [Bile acids and their therapeutic use in children].
AB  - Bile acids are natural detergents and the end-products of cholesterol metabolism.
      Their functions are mostly digestive: induction of bile flow and solubilization
      of biliary and alimentary lipids. They circulate along the enterohepatic cycle,
      and probably also along a shorter route, the cholehepatic shunt. They are
      relatively hydrophobic and perpetuate or worsen the hepatic lesions when their
      excretion is impaired in cholestasis, because of their affinity for biological
      membranes. Their functions depend on their relative hydrophilicity and
      ionization, ie on their structure and state of conjugation. They have an
      immunosuppressive effect in vivo and in vitro. Ursodeoxycholic acid (UDC) is a
      hydrophilic bile acid used in chronic cholestatic diseases. Biological
      improvement has been proven in autoimmune cholangiopathies in adults, and cystic
      fibrosis-associated liver disease in children. Clinical studies are on the way
      for other indications. It is still too early to evaluate the long-term clinical
      benefits, eg the reduction in needs for liver transplantation. UDC acid may
      induce a bicarbonate-rich hypercholeresis through the cholehepatic shunt, that
      would explain its efficacy in cystic fibrosis. In disorders of bile acid
      synthesis or transport, it could shunt the enzymatic block, or reestablish the
      bile flow through its osmotic effect. Like other bile acids it interacts with
      membranes, and is thought to stabilize them. In chronic cholestasis it would
      protect the membranes against the adverse effect of non-excreted endogenous bile
      acids. This interaction can also explain its immunosuppressive effect, through
      non-specific inhibition of transmission at the cell surface. That would explain
      the preferential clinical efficacy of UDC in autoimmune cholestasis, and
      stimulate its evaluation in "immunological" indications, such as liver
      transplantation and hepatic graft versus host disease.

PMID- 8548003
TI  - [Iron and pregnancy].
AB  - Infants, young children, and childbearing aged women are particularly exposed to
      iron deficiency. Pregnancy further increases iron requirements. Nevertheless the
      consequences of anemia and/or iron deficiency on pregnancy outcome, development
      of the foetus and postnatal iron status of the infant, remain to be determined.
      There is a 3-fold increase of premature deliveries in iron deficient anemic
      pregnant women whose anemia is discovered in early pregnancy: however this
      increased risk of premature delivery is not observed when iron deficiency anemia
      is discovered in late pregnancy. Iron supplementation during pregnancy improves
      the maternal hematological parameters but it is still unclear whether it also
      improves the maternal health and the pre and postnatal development of the child.
      Based on our actual knowledge, iron supplementation during pregnancy is to be
      recommended in risk groups only (ie mainly adolescents, low income women, women
      with multiple pregnancies), using ferrous iron at a dosage of 30 mg per day.

PMID- 8548005
TI  - [Massive intracranial hemorrhage due to avitaminosis K in a breast-fed 4 month
      old infant].

PMID- 8548004
TI  - [Radiological case of the month. A case of post-traumatic cyst-like defects].

PMID- 8548006
TI  - [Transient neonatal myasthenia gravis in premature infants: diagnostic
      difficulties and value of anticholinesterase therapy].

PMID- 8548007
TI  - [Has the campaign for the prevention of sudden infant death been effective?].

PMID- 8548008
TI  - [Saxitoxin ... this paralyzing toxin].

PMID- 8548009
TI  - High-performance liquid chromatography with mercury cathode electrochemical
      detection: application to lipid hydroperoxide analysis.
AB  - Lipid hydroperoxide species can be analyzed with high sensitivity and
      specificity, using reversed-phase high-performance liquid chromatography with
      reductive mode electrochemical detection on a mercury drop cathode [HPLC-ED(Hg)].
      The purpose of this study was to examine different variables in the operation of
      HPLC-ED(Hg) and to select optimal conditions for the analysis of several
      biologically relevant peroxides, including species derived from cholesterol,
      cholesteryl linoleate, oleate, linoleate, and two synthetic phosphatidylcholines.
      Parameters such as operating potential and mobile-phase solvent proportions,
      electrolyte composition, and ionic strength were evaluated for each peroxide
      class. Under optimal conditions, we have achieved baseline separation of four
      cholesterol hydroperoxide species, not only from one another, but also from
      phospholipid hydroperoxides; detection limits were < 0.3 pmol and < 30 pmol for
      the cholesterol and phospholipid hydroperoxides, respectively.

PMID- 8548010
TI  - Development of an assay for histamine using automated high-performance liquid
      chromatography with electrochemical detection.
AB  - Previous studies have measured histamine by derivatization with o
      phthaldialdehyde (OPA) and mercaptoethanol (ME), followed by reversed-phase HPLC
      separation and electrochemical detection. The derivatization product, however,
      was very unstable. In the present study, inclusion of less polar solvents (e.g.,
      acetonitrile or tetrahydrofuran) in the OPA/ME derivatization reaction produced
      an OPA/ME-histamine product that was stable for many hours. Changes of the HPLC
      mobile phase (increasing its ionic strength and pH and including triethylamine)
      dramatically improved the chromatography and reduced the histamine detection
      limit to < 0.1 pmol. The modified assay was suitable for batchwise manual
      derivatization of histamine samples followed by their automated analysis by HPLC
      with an automatic injector.

PMID- 8548011
TI  - Determination of vitamin K1 in serum using catalytic-reduction liquid
      chromatography with fluorescence detection.
AB  - A new method for the liquid chromatographic-fluorescence determination of serum
      vitamin K1 is described using reduction of the K-quinone to the fluorescent K
      hydroquinone. The reduction reaction occurs "on-line" in the LC system using a
      catalytic reducer column and an alcohol mobile phase as reductant. A procedure
      for serum determination utilizes a liquid-liquid serum lipid extraction followed
      by normal-phase fractionation on a solid-phase extraction cartridge. The final
      measurement uses a reversed-phase (C18) separation with a ethanol-methanol mobile
      phase and provides a detection limit of approximately 20 pg/ml.

PMID- 8548012
TI  - Isolation, structural elucidation, and partial synthesis of lutein dehydration
      products in extracts from human plasma.
AB  - All-E-(3R,6'R)-3-hydroxy-3',4'-didehydro-beta,gamma-carotene (anhydrolutein I)
      and all-E-(3R,6'R)-3-hydroxy-2',3'-didehydro-beta,epsilon-carotene (2',3'
      anhydrolutein II) have been isolated and characterized from extracts of human
      plasma using semipreparative high-performance liquid chromatography (HPLC) on a
      C18 reversed-phase column. The identification of anhydroluteins was accomplished
      by comparison of the UV-Vis absorption and mass spectral data as well as HPLC-UV
      Vis-mass spectrometry (MS) spiking experiments using fully characterized
      synthetic compounds. Partial synthesis of anhydroluteins from the reaction of
      lutein with 2% H2SO4 in acetone, in addition to anhydrolutein I (54%) and 2',3'
      anhydrolutein II (19%), also gave (3'R)-3'-hydroxy-3,4-dehydro-beta-carotene
      (3',4'-anhydrolutein III, 19%). While anhydrolutein I has been shown to be
      usually accompanied by minute quantities of 2',3'-anhydrolutein II (ca. 7-10%) in
      human plasma, 3',4'-anhydrolutein III has not been detected. The presence of
      anhydrolutein I and II in human plasma is postulated to be due to acid catalyzed
      dehydration of the dietary lutein as it passes through the stomach. These
      anhydroluteins have also been prepared by conversion of lutein diacetate to the
      corresponding anhydrolutein acetates followed by alkaline hydrolysis. However,
      under identical acidic conditions, loss of acetic acid from lutein diacetate
      proceeded at a much slower rate than dehydration of lutein. The structures of the
      synthetic anhydroluteins, including their absolute configuration at C(3) and
      C(6') have been unambiguously established by 1H NMR and in part by 13C NMR, and
      circular dichroism.

PMID- 8548013
TI  - High-performance liquid chromatographic assay for Melanotan-1 ([Nle4-DPhe7]alpha
      melanocyte-stimulating hormone) in biological matrices.
AB  - The overall objective of this research was to develop a sensitive, specific, and
      stability-indicating HPLC assay for the determination of the [Nle4-DPhe7]alpha
      melanocyte-stimulating hormone analog known as Melanotan-1 (MT-1) in biological
      matrices, i.e., cell culture transport media and human plasma. Separation was
      accomplished isocratically within 8.0 min using a C8 reversed-phase column. The
      mobile phase consisted of 0.1 M phosphate buffer-acetonitrile (80:20, v/v) with
      18 microliters/l triethylamine at pH 2.50. The flow-rate was 1 ml/min with
      detection at 214 nm. Standard curves (n = 5) were linear over the concentration
      range 100-1000 ng/ml. The precision, accuracy, intra- and inter-day variations
      were good with C.V.s typically within 8.7% for concentrations greater than 100
      ng/ml. This method was applied to a study of the transport of MT-1 in the Caco-2
      cell monolayer model.

PMID- 8548014
TI  - Assay of tocainide enantiomers in plasma by solid-phase extraction and indirect
      chiral high-performance liquid chromatography after derivatization with (-)
      menthyl chloroformate.
AB  - A fast high-performance liquid chromatographic (HPLC) assay was developed for
      determination of tocainide enantiomers in plasma. Subsequent to solid-phase
      extraction of tocainide from plasma, homochiral derivatization with (-)-menthyl
      chloroformate enabled separation of the enantiomers by a conventional reversed
      phase HPLC system. The detection was performed by UV absorption at 262 nm. An
      enantiomeric resolution of 1.0 was obtained. Linearity of the method was
      investigated and found to be good in the range from 1.0 to 20.0 micrograms/ml
      tocainide enantiomer and the limit of quantitation was 1.0 microgram/ml. The
      method was applied to a study of the distribution and elimination
      pharmacokinetics of tocainide enantiomers in the rabbit. No difference in
      distribution or elimination between the enantiomers was found nor did the
      enantiomers affect the disposition of one another when administered together as
      the racemate.

PMID- 8548015
TI  - Quantification of the individual enantiomer plasma concentrations of the
      candidate antimalarial agent N4-[2,6-dimethoxy-4-methyl-5-[(3
      trifluoromethyl)phenoxy]-8-quinolinyl] - 1,4-pentanediamine (WR 238,605).
AB  - A high-performance liquid chromatographic method was developed to quantitate the
      plasma concentrations of the individual enantiomers of a candidate 8
      aminoquinoline antimalarial agent WR 238,605 (I). The method employed one-step
      liquid extraction of a 0.5-ml plasma sample followed by direct injection of the
      extract through a chiral column and detection by fluorescence. Quantification was
      achieved using an internal standard. The limit of quantification was 10 ng/ml for
      each enantiomer. The method is sufficiently sensitive to quantitate the plasma
      concentrations of both enantiomers for 30 days following a single oral dose of
      400 mg of the antimalarial agent administered as the racemic succinate salt to
      healthy human male volunteers. In nearly all samples taken 12 h to 30 days post
      dose from three subjects, the difference in the plasma concentrations of the two
      enantiomers is less than 10%.

PMID- 8548016
TI  - High-performance liquid chromatographic analysis of the antituberculosis drugs
      aconiazide and isoniazid.
AB  - Reversed-phase HPLC methods are described for determining the stability and
      concentration certification of the antituberculosis prodrug aconiazide (ACON) in
      aqueous dosing solution and for assessing the concentrations of ACON and
      isoniazid (INH) in plasma from ACON-treated male and female Fischer-344 rats.
      ACON was analyzed in plasma by direct injection; it was separated on a 250 x 4.6
      mm I.D. 5 microns C18 column using a 40% aqueous methanol mobile phase containing
      5 g/l ammonium formate, and detected at 313 nm. INH was determined in the plasma
      of treated rats after a two-step precipitation of plasma proteins; it was
      separated on a 250 mm x 4.6 mm I.D. 5 microns CN column, eluted with 5% aqueous
      isopropanol containing 5 g/l ammonium formate, and detected with an
      electrochemical detector at +0.8 V. These methods allow a simple, rapid, and
      reliable determination of ACON and INH in plasma down to 0.1 micrograms/ml.

PMID- 8548017
TI  - Two high-performance liquid chromatographic assays for the determination of free
      and total silibinin diastereomers in plasma using column switching with
      electrochemical detection and reversed-phase chromatography with ultraviolet
      detection.
AB  - A combination of two stereoselective assays was developed using column-switching
      HPLC with electrochemical detection for the determination of free (unconjugated)
      silibinin and RP-HPLC with UV detection for the measurement of total (free and
      conjugated) silibinin in human plasma. After extraction of free silibinin and the
      internal standard hesperetin with diethyl ether the compounds were pre-separated
      on a RP-CN column. A cut fraction of eluate containing the analytes was then
      transferred to the RP-18 main column by means of a switching valve for final
      separation of the compounds. The limit of quantification with electrochemical
      detection for free silibinin was 0.25 ng/ml per diastereomer. For the
      determination of total silibinin diastereomers all conjugates were cleaved
      enzymatically using beta-glucuronidase/arylsulfatase at pH 5.6 followed by
      extraction with diethyl ether of the pH 8.5 alkalized solution. Separation of the
      diastereomers and of the internal standard naringenin was achieved on a RP-18
      column. The limit of quantification with UV detection at 288 nm for total
      silibinin was 5 ng/ml per diastereomer. Both assays were successfully applied to
      the stereospecific analysis of silibinin in plasma samples from a pharmacokinetic
      study of silymarin in human volunteers.

PMID- 8548018
TI  - Automated high-performance liquid chromatographic method for the determination of
      a neuraminidase inhibitor (GG167) in human serum by pre-column fluorescence
      derivatisation using benzoin.
AB  - A pre-column fluorescence derivatisation high-performance liquid chromatographic
      method for the analysis of a neuraminidase inhibitor, GG167, in human serum is
      described. GG167 was extracted from serum samples using Bond Elut SCX solid-phase
      extraction cartridges, followed by derivatisation with benzoin prior to reversed
      phase chromatography with fluorescence detection. This method has been automated
      using a Zymark robot and used in the analysis of human serum samples from
      clinical studies. The method has been shown to be valid over a concentration
      range of 10-800 ng/ml using a 1-ml sample volume.

PMID- 8548019
TI  - Development and validation of column-switching high-performance liquid
      chromatographic methods for the determination of a potent AII receptor
      antagonist, TCV-116, and its metabolites in human serum and urine.
AB  - Column-switching HPLC methods have been developed and validated for the
      determination of a new antihypertensive prodrug, TCV-116 (I), and its
      metabolites, CV-11974 (II) and CV-15959 (III), in human serum and urine. Initial
      sample cleanup was achieved by extracting the analytes into an organic solvent.
      After chromatographing on an ODS column with a mobile phase consisting of
      acetonitrile and an acidic phosphate buffer, the zone of the analyte's retention
      was heart-cut onto a second ODS column with a mobile phase of acetonitrile and a
      phosphate buffer at a higher pH. Complete separation of the analytes and the
      endogenous peaks was accomplished by the two-dimensional chromatography. Good
      precision and linearity of the calibration standards, as well as the inter-day
      and intra-day precision and accuracy of quality control samples, were achieved.
      The limit of quantitation (LOQ), using 0.5 ml of serum, was 2 ng/ml for I, 0.8
      ng/ml for II, and 0.5 ng/ml for III. The LOQ for urine sample was 10 ng/ml for II
      and III. Stability of the analytes during storage, extraction, and chromatography
      processes was established. The results illustrate the versatile application of
      column switching to method development of multiple analytes in various biological
      matrices. The methods have been successfully used for the analyses of I and its
      metabolites in thousands of clinical samples to provide pharmacokinetic data.

PMID- 8548020
TI  - Development and validation of a gradient reversed-phase high-performance liquid
      chromatographic assay for S(-)-2-(N-propyl-N-2-thienylethylamino)-5
      hydroxytetralin (N-0923) from a transdermal delivery system.
AB  - A gradient reversed-phase HPLC method for potency determination of N-0923 (10 mg)
      from a transdermal delivery system (TDS), was developed and validated with single
      point calibration using internal standard quantitation. N-0923 and the internal
      standard, N-0434, are eluted from a reversed-phase C18 column using a gradient
      which contains 0.1 M triethylamine-0.04 M citrate buffer, pH 5.9, water, and
      acetonitrile with UV detection at 272 nm. N-0923 is isolated from the transdermal
      delivery system by extraction with n-heptane followed by extraction of the
      resulting organic phase with 0.1 M citric acid containing the internal standard.
      The method was free from matrix interferences in both untreated and forced
      degraded placebo delivery systems. Acceptable linearity and quantitative recovery
      from spiked placebo delivery systems over the range 50-150% of nominal label
      claim were demonstrated. Within-day assay precision from individual samples of
      active transdermal delivery systems (n = 10) was 5.6% R.S.D. The detection limit
      was at least 0.1 microgram/ml which is equivalent to 0.05% of the working
      standard concentration. Replicate injection precision at this level was 0.08%
      R.S.D. (n = 4). Analysis of thermally stressed active and placebo delivery
      systems with this HPLC method and photodiode-array detection showed that the
      chromatography was stability-indicating as demonstrated by the absence of
      measurable interferences from principal degradation products of either the n-0923
      or the delivery system excipients.

PMID- 8548021
TI  - High-performance liquid chromatographic determination of irinotecan (CPT-11) and
      its active metabolite (SN-38) in human plasma.
AB  - A simplified method for the simultaneous determination of irinotecan (CPT-11, I)
      and its active metabolite (SN-38, II) in human plasma by high-performance liquid
      chromatography (HPLC) with fluorescence detection has been developed. Following
      the addition of the internal standard (I.S.) camptothecin, the drugs were
      extracted from plasma using methanol. The average extraction efficiencies were
      87% for I, 90% for II and 90% for the I.S. Chromatography was performed using a
      TSK gel ODS-80Ts column, monitored at 556 nm (excitation wavelength, 380 nm) and
      the mobile phase was acetonitrile-50 mM disodium hydrogen phosphate (28:72)
      containing 5 mM heptanesulphonate (pH 3.0). The linear quantitation ranges for I
      and II were 30-2000 and 1-30 ng/ml, respectively.

PMID- 8548022
TI  - Liquid chromatographic-atmospheric pressure chemical ionization mass
      spectrometric analysis of glycine conjugates and urinary isovalerylglycine in
      isovaleric acidemia.
AB  - n-Acetylglycine, n-propionylglycine, n-butyrylglycine, isobutyrylglycine, n
      valerylglycine, isovalerylglycine, heptanoylglycine, phenylacetylglycine and
      isovalerylglucuronide were identified based on their liquid chromatographic
      atmospheric pressure chemical ionization mass spectra (LC-APCI-MS). We were able
      to detect the presence of urinary isovalerylglycine in two cases of isovaleric
      acidemia using LC-APCI-MS. Membrane-filtered urine samples were injected into the
      LC-APCI-MS system in the negative-ion mode without any further pretreatment, and
      large amounts of isovalerylglycine were detected as the [M-H]- ion. The urinary
      excretion of isovalerylglycine appeared to increase after L-carnitine therapy.
      This analytical method is quick and easy and it may be a useful tool in
      understanding dysfunctional conditions in isovaleric acidemia.

PMID- 8548024
TI  - Routine high-performance liquid chromatographic determination of myocardial
      interstitial norepinephrine.
AB  - The present study describes a high-performance liquid chromatographic
      electrochemical detection (HPLC-ED) system for routine measurement of the low
      levels of norepinephrine (NE) found in the myocardial interstitial space. In this
      system, an in vivo detection limit of 100 fg in a 50-microliters injection was
      achieved for NE. Using cardiac dialysis technique, 20-microliters dialysates were
      sampled from the myocardial interstitial space at 2-min intervals. The basal
      dialysate NE concentration was 16.6 +/- 4.0 pg/ml. This low detection limit
      allowed the dialysate NE concentration to be monitored for dysfunction of the
      cardiac sympathetic nerve terminal. This system offers a new possibility for
      routine analysis of myocardial interstitial NE levels.

PMID- 8548023
TI  - Detection of basal acetylcholine in rat brain microdialysate.
AB  - A liquid chromatography-electrochemistry (LC-EC) method is described for the
      determination of basal acetylcholine (ACh) in microdialysate from the striatum of
      freely moving rats. This method is based on the separation of ACh and choline
      (Ch) by microbore liquid chromatography followed by passage of the effluent
      through a post-column immobilized enzyme reactor (IMER), containing
      acetylcholinesterase (AChE) and choline oxidase (ChO), and then the
      electrochemical detection of the hydrogen peroxide produced. Instead of the
      conventional platinum electrode generally used for the anodic detection of
      hydrogen peroxide, a peroxidase-redox polymer modified glassy carbon electrode
      operated at + 100 mV vs. Ag/AgCl has been used to detect the reduction of
      hydrogen peroxide. With this method, a detection limit of 10 fmol (injected) for
      ACh (S/N = 3:1) was obtained and the basal ACh concentration in striatal
      microdialysate was determined without using esterase inhibitors.

PMID- 8548025
TI  - Determination of plasma activities of purine nucleoside phosphorylase by high
      performance liquid chromatography: estimates of nonparenchymal cell injury after
      porcine liver transplantation.
AB  - An assay is described for measurement of purine nucleoside phosphorylase (PNP) in
      plasma by high-performance liquid chromatography (HPLC). A plasma sample was
      incubated with hypoxanthine and ribose-1-phosphate in phosphate-free medium at pH
      7.4 to catalyse the production of inosine by plasmatic PNP. The reaction was
      stopped by addition of perchloric acid to inactivate the enzyme and to
      precipitate plasma proteins. After centrifugation and neutralization of the
      supernatant with NaOH the increase in the substrate inosine was determined by
      HPLC. Plasma activities of PNP averaged 5.0 mU/ml before and 12.3 mU/ml (p <
      0.001), 5 min after porcine liver transplantation. At the same time points, the
      plasma activities of the frequently used liver enzymes lactate dehydrogenase or
      alanine aminotransferase remained virtually unchanged. Thus, plasmatic activities
      of PNP may be a suitable and early indicator of ischemic alterations to the graft
      in vivo.

PMID- 8548026
TI  - Separation and identification of carotenoids in bird's plumage by high
      performance liquid chromatography--diode-array detection.
AB  - The coloured feathers of Carduelis spinus (Siskin), C. flammea (Redpoll), Serinus
      serinus (Serin), Loxia curvirostra (Crossbill), Pinicola enucleator (Grossbeak),
      Carpodacus roseus (Pallas Rosefinch) and Pyrrhula pyrrhula (Bullfinch) have been
      extracted with a new procedure using mild conditions (a few minutes at room
      temperature). After the separation of melanines and proteins, the extracts were
      analyzed by HPLC-MS and HPLC-UV-Vis. The main components of the pigments were
      identified in all the species examined; moreover, UV-Vis and MS data were
      collected also for the minor components. These data suggest that minor components
      are generally cis isomers accompanying the predominant all-trans isomers.

PMID- 8548027
TI  - Mass spectrometric analysis of haemoglobin adducts formed by methyl bromide in
      vitro.
AB  - An analytical procedure is described for the identification of the adducts formed
      by interaction of methyl bromide and haemoglobin. The reaction products of in
      vitro incubation of haemoglobin with methyl bromide have been characterised by
      electrospray mass spectrometry and gas chromatography-mass spectrometry. A
      prominent reactivity of several potential nucleophilic sites of haemoglobin was
      observed. Analogous results were recorded on blood samples of workers exposed to
      methyl bromide. The results obtained represent the basis for the complete
      structural characterisation of the modified haemoglobin and demonstrate the
      usefulness of the proposed analytical approach for the evaluation of alkylation
      degree and the identification of modified amino acids in proteins.

PMID- 8548028
TI  - Simple and rapid analysis of lamotrigine, a novel antiepileptic, in human serum
      by high-performance liquid chromatography using a solid-phase extraction
      technique.
AB  - A simple and rapid method for the quantitation of concentrations of lamotrigine,
      a novel antiepileptic, in human serum was developed with high-performance liquid
      chromatography, using a solid-phase extraction technique. The mobile phase was
      composed of acetonitrile-10 mM phosphate buffer (pH 3.5) containing 5 mM sodium
      octanesulphonate (27:73, v/v), and components were detected at 265 nm. Retention
      times of acetanilide as an internal standard and lamotrigine were 3.4 and 10.3
      min, respectively. The coefficients of variation were 3.1-4.5% and 4.4-9.8% for
      the within-day and between-day precision estimates, respectively. The extraction
      recovery of lamotrigine added to blank serum was 86-107%. The quantitation limit
      of lamotrigine was ca. 0.2 microgram/ml in 100 microliters of serum. These
      results suggest that the method employed in this study is useful for the routine
      monitoring of serum concentrations of lamotrigine in epileptic patients.

PMID- 8548029
TI  - Phenytoin free fraction determination: comparison of an improved direct serum
      injection high-performance liquid chromatographic method to ultrafiltration
      coupled with fluorescence polarization immunoassay.
AB  - Recent developments in restricted-access media (RAM) liquid chromatography make
      the simultaneous determination of total and free phenytoin concentrations
      possible by direct injection of drug-containing serum samples. A comparison of
      phenytoin free fraction determination by ultrafiltration coupled with
      fluorescence polarization immunoassay (TDX) to an improved direct injection RAM
      HPLC method is presented. Our improved method differs from those previously
      reported with regard to column type, mobile-phase composition, and column
      temperature. Replicate samples analyzed by each method yielded similar values for
      serum phenytoin free fraction.

PMID- 8548030
TI  - High-performance liquid chromatographic determination of 4,4'
      dihydroxybenzophenone-2,4-dinitrophenylhydrazone in plasma.
AB  - An analytical method has been developed for the determination of 4,4'
      dihydroxybenzophenone-2,4-dinitrophenylhydrazone (I, trade name A-007) in plasma.
      Plasma samples are primed with the internal standard, 2,2'-dihydroxybenzophenone
      2,4-dinitrophenylhydrazone (II), deproteinized with acetonitrile, centrifuged and
      filtered prior to assay. The components are then separated on a reversed-phase
      column with retention times of 4.4 and 6.0 min for I and II, respectively.
      Ultraviolet detection at 365 nm was employed and little interference with the
      analyte or the internal standard was noted from other plasma components. This
      method has been applied to the plasma of rats and monkeys doses for
      pharmacokinetic and toxicity studies.

PMID- 8548031
TI  - High-performance liquid chromatographic determination of iobitridol in plasma,
      urine and bile.
AB  - Iobitridol is a new non-ionic, low-osmolality contrast medium for urography and
      angiography. We have developed a method for determining iobitridol in body fluids
      using high-performance liquid chromatography with ultraviolet detection. The
      method, which is specific and reproducible, does not require an internal
      standard. Determinations can be carried out in body fluids against a set of
      standards in ethanol. The method was validated for the quantification of
      iobitridol in biological samples obtained during pharmacokinetic studies.

PMID- 8548032
TI  - Rapid and efficient method for extraction and separation of glucocorticosteroids
      and sex steroids from urines.
AB  - The influence of different pH values on the recoveries of glucocorticosteroids
      and sex steroids from Kieselguhr-filled minicolumns has been investigated. While
      the recoveries of all steroids tested were similar if samples had acidic or
      neutral pH values, sex steroids could effectively be separated from
      glucocorticosteroids by increasing the pH value to 13.7: recoveries were 1.7% for
      glucocorticosteroids and 56-76% for sex steroids. For the determination of sex
      steroids in biological samples it is recommended to adjust samples to a strong
      alkaline pH before extraction; this holds especially true for samples with very
      high glucocorticosteroid levels.

PMID- 8548033
TI  - Automated determination of hypoxanthine and xanthine in urine by high-performance
      liquid chromatography with column switching.
AB  - We report a high-performance liquid chromatographic method with column switching
      for urinary hypoxanthine and xanthine. Analyses were carried out with both a
      reversed-phase column and an anion-exchange column connected by a column switch
      and controlled automatically by a computerized system controller. The
      relationships between standard concentrations and peak heights were linear in a
      concentration range of 1 to 1000 nmol/ml. The recovery of hypoxanthine added to
      urine was 101.1%, and that of xanthine was 98.1%. With our method urinary
      hypoxanthine and xanthine can be measured accurately without any sample
      preparation other than filtration.

PMID- 8548034
TI  - Limitations of podocyte adaptation for glomerular injury in puromycin
      aminonucleoside nephrosis.
AB  - Glomerular synechiae that occurred in nephrotic rats with a single
      intraperitoneal injection of puromycin aminonucleoside were analyzed by
      immunohistochemistry, radiolabeled thymidine ([3H]-thymidine) autoradiography, as
      well as light, electron and immunoelectron microscopy. To discriminate podocytes
      from parietal epithelial cells (PEC) and monocytes, monoclonal antibodies (mAb)
      against podocalyxin and ED1 were used. The cell kinetics of glomerular epithelial
      cells were autoradiographically assessed with isotope labeling procedures before
      and during nephrosis (co-labeled), and a mAb against proliferating cell nuclear
      antigen (PCNA). All the cell types except the podocyte of normal kidneys were
      labelled with [3H]-thymidine at different rates. Detachment of degenerated
      podocytes from the outside of the glomerular basement membrane (GBM) is the first
      step of synechia, and detached sites are confronted by PEC that were
      hypertrophied and frequently radiolabeled. Evidence that podocytes in glomeruli
      of nephrotic rats can proliferate was shown by the presence of mitoses, [3H]
      thymidine uptake in the co-labeled experiment, and by PCNA staining, but re
      epithelialization over bare segments of the GBM with proliferated podocytes is
      doubtful. It was concluded that glomerular synechia resulted from the limits of
      podocyte adaptation to glomerular injuries.

PMID- 8548035
TI  - Immunohistochemical localization of C-reactive protein-binding sites in human
      atherosclerotic aortic lesions by a modified streptavidin-biotin-staining method.
AB  - One-step fluorescein-conjugated polyclonal antibody technique has shown that C
      reactive protein (CRP) was located only extracellularly in human atherosclerotic
      lesions. In this report a more sensitive streptavidin-biotin technique was
      applied to detect the localization of CRP in human atherosclerotic lesions.
      Immunohistochemical staining with polyclonal and monoclonal anti-human CRP
      antibodies both produced a brown color extracellularly in the necrotic lesions,
      and intracellularly in CD68+ foam cells. The latter suggests an uptake of CRP
      lipid complexes by macrophages. The staining is human CRP-specific because it was
      eliminated by preabsorption of the monoclonal antibody with pure human CRP, or by
      substitution of the primary antibody with non-immune rabbit serum. By overlaid
      CRP-binding study, a positive stain was observed on intimal smooth muscle cells
      and foam cells, suggesting that they have CRP-binding sites unless the CRP
      binding activity was generated de novo through the fixation procedure.
      Accordingly, it is hypothesized that CRP may facilitate the uptake of lipids by
      macrophages accumulating in atherosclerotic lesions. Further, CRP might
      participate in cytolysis, which enlarges the necrotic area, and/or in
      phagocytosis that scavenges the necrotic tissue.

PMID- 8548036
TI  - Structural characteristic of splenic sinuses in idiopathic portal hypertension.
AB  - Splenic sinuses in idiopathic portal hypertension (IPH; 8 patients), liver
      cirrhosis (LC; 14 patients) and in regenerating autotransplanted spleens from 25
      rats were compared with each other by scanning electron microscopy (SEM) and
      immunohistochemistry using antibodies against proliferating cell nuclear antigen
      (PCNA). Spleens obtained from six patients with gastric carcinoma and from five
      untreated adult rats were examined as controls. SEM of the sinuses showed that in
      IPH endothelial cells became irregular in shape, and the interendothelial slits
      of sinuses were irregularly enlarged. Sinus endothelial processes traversing the
      sinusal lumen were also found. The same changes were observed in the
      proliferating sinuses during regeneration of splenic tissue after
      autotransplantation in rats, but disappeared when the regeneration was completed.
      Irregular endothelial cells were few in LC. PCNA-positive sinus endothelial cells
      were increased in number in IPH as compared with those in LC; the mean number of
      PCNA-positive ones per cm2 was 45.4 in IPH and 8.2 in LC. It was suggested that,
      from SEM observation of sinus endothelial cells and counting PCNA-positive sinus
      endothelial cells, the sinuses of the spleen in IPH consist of proliferating
      endothelial cells or are in the state of increased proliferation. In conclusion,
      splenomegaly in IPH was presumed to be caused by proliferation of sinus
      endothelial cells, and by the increased splenic blood flow in the irregularly
      widened interendothelial slits of the sinuses.

PMID- 8548038
TI  - Presence of eosinophilic precursors in the human thymus: evidence for intra
      thymic differentiation of cells in eosinophilic lineage.
AB  - The distribution of myeloid cells in the human thymus was investigated by light
      and electron microscopy, immunohistochemistry, and/or flow cytometry. A series of
      74 thymic samples, from newborn to 37 year old patients, were studied. By light
      microscopy, aggregates of mononuclear cells were frequently present in
      intralobular septa and outer medulla. Among those cells, eosinophilic precursors
      (promyelocyte, myelocytes and metamyelocytes) were readily identified. These
      immature granular cells were present in all pre-involutional thymi, and were
      particularly frequent in the thymi of patients who were younger than 5 years of
      age. The cells made up 30-50% of the total eosinophilic population and were
      frequently observed as a group of cells at various stages of differentiation,
      suggesting that they differentiate from pre-existing precursors in the thymus.
      These eosinophilic precursors were mostly located in the intralobular septa and
      fibroreticular network at the corticomedullary junction, while mature eosinophils
      were scattered throughout the thymus. Flow cytometric analyses, using stem cell
      enriched preparations, showed that cells expressing CD33 or CD34 constituted on
      average 2.55% and 3.33% (0.09% and 0.12% of the total cells), respectively.
      CD33+/CD34+ coexpressors were also identified, and they constituted 0.36% of the
      analyzed cells (0.01% of the total cells). No statistical difference in the
      proportions of CD33+ and/or 34+ cells was noted between any age groups. It is
      concluded that eosinophilic precursors present in the thymus differentiate into
      cells in the eosinophilic lineage in particular areas such as the intralobular
      septa and fibroreticular network of the outer medulla in preinvolutional human
      thymi.

PMID- 8548037
TI  - p53 mutation in carcinomas arising in ovarian cystic teratomas.
AB  - Carcinomas arising in mature cystic teratomas of the ovaries from nine women were
      examined for the presence of p53 mutations. The nine tumors comprised six
      squamous cell carcinomas, one squamous cell carcinoma in situ, one
      undifferentiated small cell carcinoma, and one mucoepidermoid carcinoma. Abnormal
      nuclear accumulation of the p53 protein was observed in four of the tumors.
      Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue blocks
      and subjected to polymerase chain reaction (PCR) for specific amplification of
      the p53 gene exons 5-8, followed by direct chemiluminescence sequencing analysis.
      A frameshift mutation in exon 8 (codon 278, CCT > del T; stop at codon 344) was
      detected in one poorly differentiated squamous cell carcinoma. The samples were
      also evaluated for the possible association of 'benign' and 'malignant' types of
      human papillomavirus (HPV) by PCR using universal primer sets. None of the
      samples contained detectable HPV genome. These data suggest that p53 mutations
      are relatively uncommon in secondary carcinomas developing in ovarian dermoid
      cysts, although the number of samples studied was admittedly small.

PMID- 8548039
TI  - Poorly differentiated ('insular') carcinoma of the thyroid.
AB  - Three cases of unusual poorly differentiated ('insular') carcinoma of the thyroid
      gland are presented. These three thyroid carcinomas were large; the tumors from
      patients 1 and 3 were encapsulated, and that from patient 2 showed invasive
      growth. Microscopically the tumors were characterized by well-defined solid nests
      (insulae), which were composed of rather small and uniform tumor cells with round
      to oval nuclei. Formation of small and colloid-containing follicles was
      associated with these nests to varying degrees. The tumors of patients 1 and 3
      were composed entirely of insular components, but that of patient 2 was
      associated with small areas of well-differentiated follicular carcinoma. The
      metastatic tumors of patients 1 and 2 were essentially similar to the primary
      with small foci of follicular carcinoma. Patient 1 is alive with local and
      mediastinal node recurrences, but patient 2 died of the disease with local
      recurrences and metastases to lungs, bones and skin. Patient 3 had no recurrences
      and died of unrelated disease 5 years after surgery. The present study indicates
      that insular carcinomas have characteristic histologic features and a less
      favorable prognosis, confirming the findings of previous studies.

PMID- 8548040
TI  - Duct-acinar-islet cell tumor of the pancreas.
AB  - A case of a rare pancreatic tumor, duct-acinar-islet cell tumor is presented. The
      tumor was incidentally found in the pancreatic body on computed tomography of a
      21 year old male suffering from mumps. It was well demarcated from surrounding
      pancreas, and spherical in shape, measured 2.5 cm in diameter. Histologic and
      immunohistochemical examinations showed the tumor to consist of three distinct
      cell populations: duct, acinar and islet cells. Small cell nests consisting of
      these cellular components, either solely of one cell type or mixed of the three
      cell types, were separated by broad desmoplastic stroma. Islet (endocrine) cells,
      which were most predominant, were arranged in a trabecular pattern or small cell
      nests. Most of them were positive for glucagon, and a few cells expressed
      insulin, somatostatin, serotonin or pancreatic polypeptide. These cells were
      distributed randomly within the cell nests. Ducts, some of which contained goblet
      cells, were found among the endocrine cell nests. Duct-islet complexes were also
      observed. The acinar cells were the least conspicuous component. They expressed
      pancreatic alpha-amylase. An electron microscopic examination revealed duct cells
      with intercellular attachments and interdigitations, endocrine cells containing
      secretory granules, and acinar cells with zymogen granules. No definite evidence
      suggesting malignancy could be obtained.

PMID- 8548041
TI  - Myoepithelial carcinoma in pleomorphic adenoma of salivary gland type, occurring
      in the mandible of an infant.
AB  - A rapidly growing mandibular tumor occurred in a 17 month old female infant.
      Tumor outgrowth showing a periosteal reaction was radiographically seen on the
      lower surface (base) of the mandible. Under the biopsy diagnosis of osteosarcoma,
      high-dose chemotherapy with methotrexate was performed, resulting in little
      effect. The right hemimandibulectomy specimen disclosed intraosseous infiltrative
      growth of pleomorphic adenoma of salivary gland type, associated with chondroid
      stroma and reactive bone formation. The highly proliferative small-sized cells
      retained immunohistochemical features of myoepithelial cells, with positive
      reactivity of cytokeratin, vimentin, S-100 protein, alpha-smooth muscle actin,
      epithelial membrane antigen, CA15-3, type IV collagen, laminin and p53 protein.
      No heterotopia of the salivary gland was identified within the bone tissue. The
      tumor recurred 2 months later. Due to uncontrollable local growth, the patient
      died 8 months after operation. At autopsy, reactive ossification was closely
      associated with malignant myoepithelial proliferation. No distant metastasis was
      noted. This osteosarcoma-like tumor can be regarded as myoepithelial carcinoma in
      pleomorphic adenoma, originating from intramandibular heterotopic salivary gland
      tissue.

PMID- 8548042
TI  - Clear cell chondrosarcomas arising from rare sites.
AB  - Three cases are reported of clear cell chondrosarcoma arising from unusual sites:
      talus, rib and vertebra. Radiographically, two tumors showed osteolytic features
      and the vertebral tumor showed osteoplastic change. Histologically, all tumors
      consisted of clear cells that had a centrally placed nucleus surrounded by clear
      cytoplasm, osteoclast-like giant cells, areas of conventional chondrosarcoma, and
      various amounts of reactive bone. The tumor in the talus was initially diagnosed
      as benign chondroblastoma, but it recurred. The rib tumor showed marked cystic
      formation stimulating aneurysmal bone cyst. The osteoplastic radiographic feature
      in vertebral tumor was considered to be due to the abundant bone formation.

PMID- 8548043
TI  - Leiomyosarcoma of the superior vena cava producing superior vena cava syndrome
      and heart tamponade.
AB  - An autopsy case of primary leiomyosarcoma arising in the superior vena cava is
      presented. A 44 year old Japanese man presented with superior vena cava syndrome
      and eventually died due to heart tamponade and acute renal failure. Autopsy
      revealed that the superior vena cava was occluded with a tumor that had invaded
      the pericardium and right thoracic cavity. Primary caval venous leiomyosarcoma is
      a rare but lethal disease and most cases arise from the inferior vena cava. This
      case represents a very rare case of leiomyosarcoma with the rare clinical
      findings of superior vena cava syndrome and heart tamponade.

PMID- 8548044
TI  - Localization of Epstein-Barr virus genome in lymphoid cells in poorly
      differentiated adenocarcinoma with lymphoid stroma of the colon.
AB  - Poorly differentiated adenocarcinoma with lymphoid stroma occurred in the
      transverse colon of a 77 year old female. Numerous small lymphocytes and plasma
      cells were distributed in the tumor stroma. Non-isotopic in situ hybridization
      study for Epstein-Barr (EBV)-related small nuclear RNA (EBER-1) revealed positive
      signals in the nuclei of a few lymphocytes in the tumor stroma, while the tumor
      cell nuclei were not labeled. Immunostaining for latent membrane protein-1 was
      negative. The significance of detection of the EBV-infected lymphocytes in the
      colon tumor stroma is discussed.

PMID- 8548046
TI  - Effects of growth hormone and insulin-like growth factor I on the immune system.
AB  - Growth hormone-releasing hormone (GHRH), growth hormone (GH), prolactin (PRL) and
      insulin-like growth factor I (IGF-I) are synthesized and secreted by various
      immunocompetent cells. In addition, GHRH, GH, PRL and IGF-I receptors are
      expressed on immune cells. Growth hormone, PRL and IGF-I stimulate the
      proliferation of immunocompetent cells and modulate humoral and cellular immune
      functions, i.e. immunoglobuline secretion of B cells, thymulin secretion of
      thymic epithelial cells, natural killer cell activity, phagocytosis, oxidative
      burst and killing capacity of neutrophils and macrophages. No clinically
      significant cellular or humoral immunodeficiency has been found in GH-deficient
      patients. However, several immunological parameters and functions are altered in
      GH-deficient patients when compared to normal controls. The data available to
      date indicate that endocrine and pleiotropic para- and autocrine mechanisms of
      action are involved in a neuropeptide immune network, including GH, PRL and IGF-I
      as modulators of immune function.

PMID- 8548045
TI  - CD68+ reactive histiocytosis complicating early gastric cancer.
AB  - A peculiar form of reactive, non-granulomatous proliferation of CD68+ histiocytes
      was demonstrated, for the first time, in the submucosal layer just beneath the
      IIa-type early gastric adenocarcinoma that focally invaded submucosal lymphatics.
      The histiocytic cells possessed plump eosinophilic and often foamy cytoplasm and
      eccentric small nuclei with apparent nucleoli. They contained periodic acid
      Schiff-reactive granules, and were further immunoreactive for lysozyme and alpha
      1-antitrypsin. The infiltration was ill-defined, and partly involved the tunica
      muscularis mucosae and the proper muscle layer. Markers of epithelial cells,
      Langerhans' histiocytes, smooth muscle cells and myofibroblasts were all
      negative.

PMID- 8548047
TI  - Influence of thyroid hormones on the regulation of growth hormone secretion.
AB  - The effects of thyroid hormones on GH secretion and the mechanisms underlying
      their action are very similar in man and the laboratory animal. We feel that it
      is possible to organize the available data into a unique pathophysiological model
      explaining these complex interactions (Table 1). In summary, physiological levels
      of circulating thyroid hormones are necessary to maintain normal pituitary GH
      secretion owing to their direct stimulatory actions. When the serum
      concentrations of thyroid hormone increase above the normal range there is an
      increase in hypothalamic somatostatin tone, which in turn suppresses pituitary GH
      secretion and overrides any stimulatory effects. The suppression of GH secretion
      by thyroid hormones may be mediated at the hypothalamic level also by a decrease
      in GHRH release.

PMID- 8548048
TI  - Growth hormone receptor: structure and signal transduction.
AB  - The growth hormone receptor (GHR) belongs to the superfamily of transmembrane
      proteins that includes the prolactin receptor and a number of cytokine receptors.
      Two forms exist for the GHR: the full-length membrane-bound human receptor is a
      protein of 620 amino acids with a single transmembrane region; and the GH binding
      protein (GHBP) is a short soluble from corresponding to the extracellular domain
      of the full-length receptor. In rodents, GHBP is encoded by a specific mRNA of
      1.2-1.5 kb, whereas in man and other species GHBP is believed to result from
      proteolytic cleavage of the membrane receptor. Growth hormone binding protein
      prolongs the half-life of GH but other functions for GHBP remain to be
      demonstrated. Recombinant GHBP complexed to human GH shows a 2:1 stoichiometric
      crystal structure. Growth hormone-induced dimerization of the cell surface GHR
      appears to be a prerequisite for biological activity of the hormone. JAK2 has
      been identified as a tyrosine kinase associated with GHR and other receptors of
      the superfamily. Binding of GH to its receptor results in dimerization of the
      GHR, phosphorylation of JAK2 and of the GHR. Other substrates for JAK2 have to be
      identified. Transcription factors belonging to the STAT (signal transducers and
      activators of transcriptions) family are involved in the transcriptional effects
      of GH. The activity of mutants of the GHR has been measured in functional tests
      to identify sequences of the cytoplasmic domain of the receptor that are
      important for signal transduction. A proline-rich sequence, called Box I,
      conserved among members of the receptor family has been shown to be crucial for
      GH effects on gene transcription. MAP kinase activity and cell proliferation. The
      C-terminal region of the GHR is required for tyrosine phosphorylation of the
      receptor and for a hormonal effect on gene transcription, whereas only 46
      membrane proximal amino acids of the cytoplasmic domain are necessary for
      activation of JAK2 and transduction of the GH proliferative signal. Much work
      remains to be done to identify other protein kinases and signalling molecules
      involved in the mechanism of action of GH.

PMID- 8548049
TI  - Cytokines and the endocrine system. I. The immunoendocrine network.

PMID- 8548050
TI  - Medical therapy with somatostatin analogues for acromegaly.

PMID- 8548051
TI  - Effects in skeletal muscle of supraphysiological growth hormone stimulation.

PMID- 8548052
TI  - Impairment of lung volumes and respiratory muscle strength in adult patients with
      growth hormone deficiency.
AB  - Little is known of the respiratory function in patients with growth hormone (GH)
      deficiency. The aim of the present study was to evaluate lung volumes and
      respiratory muscle strength in patients diagnosed as GH deficient in childhood.
      Ten patients diagnosed as GH deficient in childhood and ten healthy subjects
      entered the study. For each subject the evaluation of respiratory function
      followed the same standard approach, consisting of respiratory muscle strength
      assessment, recording of flow-volume curves, measurement of static lung volumes
      and lung diffusing capacity. Both maximal inspiratory and expiratory mouth
      pressures were decreased in GH deficiency. Vital capacity, N2 functional residual
      capacity and total lung capacity were significantly reduced when compared to
      healthy subjects. Conversely, the residual volume and diffusing lung capacity to
      CO did not show any significant change. No significant change of percentage
      forced expiratory volume in 1 s/forced vital capacity ratio was observed. The
      decrease of respiratory mouth pressures was not correlated to the decrease of
      lung volumes. In conclusion, the results of this study show that adult patients
      affected with childhood onset GH deficiency suffer from impairment of ventilatory
      function and a decrease of respiratory muscle pressures, probably due to
      reduction of respiratory muscle strength.

PMID- 8548053
TI  - In vivo responsiveness of morphological variants of growth hormone-producing
      pituitary adenomas to octreotide.
AB  - The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH)
      secretion that has been used to treat patients with GH-producing pituitary
      tumors. In this study we investigated the in vivo responsiveness to treatment
      with this analog in patients harboring different morphological types of GH
      producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I)
      plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4
      months preoperatively were compared with those from 30 patients who did not
      receive treatment preoperatively. Tissue samples were studied using
      ultrastructural and immunohistochemical techniques. Amongst patients harboring
      densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by
      octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both
      interventions. Surgery was equally as effective in lowering GH levels in patients
      with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in
      patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16%
      and to 24 +/- 15% when performed following octreotide pretreatment. In contrast,
      treatment with octreotide alone in patients harbouring SG adenomas reduced GH
      levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or
      surgery and octreotide). We conclude that the GH inhibitory effects of octreotide
      are significantly better in patients harboring DG somatotroph adenomas compared
      with those harboring SG adenomas.

PMID- 8548054
TI  - Melatonin enhances cortisol levels in aged but not young women.
AB  - In spite of animal data showing an effect of melatonin in the regulation of the
      hypothalamus-pituitary-adrenal (HPA) axis, no effect of melatonin on cortisol has
      been evidenced in young men. Gender and aging are believed to influence the
      regulation of the HPA axis, and may thus modulate the melatonin effect on
      cortisol. In this study we investigated whether an effect of melatonin on
      cortisol can be observed in women of different age. Six young women in early
      follicular phase (22-32 years; EFW) and eight aged women in postmenopause (54-62
      years; PMW) were studied. At 08.00 h on two consecutive days each woman received,
      randomly and in double-blind fashion, a pill of placebo or melatonin (100 mg).
      Serum levels of melatonin and cortisol were evaluated at 20-min intervals for 48
      h. In comparison to EFW, PMW showed an earlier onset of nocturnal melatonin (p <
      0.05) and cortisol rise (p < 0.01) and higher cortisol levels at lunch (p < 0.05)
      and early evening (p < 0.01). Melatonin administration did not modify serum
      cortisol levels in EFW but elicited a marked increase of daytime cortisol levels
      in PMW (p < 0.02). The present data reveal that in aged PMW the cortisol levels
      are enhanced at selected circadian times and are stimulated by melatonin.

PMID- 8548055
TI  - High-dose progesterone infusion in healthy males: evidence against
      antiglucocorticoid activity of progesterone.
AB  - High concentrations of unbound cortisol in late pregnancy have been explained by
      the antiglucocorticoid activity of high progesterone levels. To further test this
      hypothesis we studied the effect of high-dose progesterone on baseline and
      corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a
      double-blind crossover study eight healthy male volunteers received either
      progesterone (0.714 mg.kg-1.h-1 for 60 min followed by a dose of 0.45 mg.kg-1.h-1
      over a total infusion time of 315 min) or vehicle as a continuous intravenous
      infusion. At 210 min a CRH test (0.1 microgram/kg body weight as bolus iv) was
      performed. Within 30 min after the start of progesterone administration the serum
      progesterone level increased to 454 +/- 31 nmol/l and remained in the range of
      third trimester pregnancy concentrations throughout the infusion period. During
      vehicle infusion the progesterone level remained in the normal range for healthy
      males and demonstrated a small but significant increase after CRH (1.52 +/- 0.23
      vs 0.74 +/- 0.14 mmol/l; p < 0.01). However, baseline and CRH-stimulated serum
      cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose
      progesterone. Moreover, unbound salivary cortisol also was not affected by
      progesterone, suggesting that there is no significant competition for transcortin
      binding sites. In conclusion, no antiglucorticoid activity was found after short
      term administration of progesterone in males. These findings cast doubts on the
      concept that the alterations of the pituitary-adrenal axis in late pregnancy are
      induced by the antiglucocorticoid activity of high progesterone concentrations.

PMID- 8548056
TI  - Regulation of luteal function by luteinizing hormone and prolactin at different
      times of the luteal phase.
AB  - In 54 healthy women luteal function was assessed by sequential withdrawals of
      blood samples at 10-min intervals for 8-10 h. Subgroups of the women were studied
      during the early and late ovulatory period and during the early, mid- and late
      luteal phase. Bio- and immunoreactive luteinizing hormone (LH), prolactin,
      testosterone, estradiol and progesterone levels were determined in each sample.
      While the bio- and immunoreactivity of LH pulses correlated fairly well, a number
      of bio- or immunoreactive LH pulses were observed that were not detected by the
      respective other method. Responsivity of the corpus luteum to LH episodes
      developed during the second half of the luteal phase and was most marked in cases
      where LH episodes were accompanied by prolactin episodes. In the absence of
      prolactin episodes. LH episodes did not stimulate progesterone or estradiol
      secretion. The highest incidence of coincident LH and prolactin pulses was
      observed during the mid- and late luteal phase. Serum testosterone levels showed
      also some fluctuations but these were independent of immuno- or bioactive LH
      episodes and therefore most likely not of luteal origin. Prior to menstruation LH
      episodes were not any more stimulatory to progesterone secretion, indicating that
      it is not the withdrawal of LH but, rather, another possibly intraovarian
      mechanism that results in luteolysis. In a number of women, increased estradiol
      and progesterone secretion was strictly related to the prior occurrence of LH and
      prolactin pulses. In other subjects, both gonadal steroids fluctuated largely
      with no discernible correlation to LH fluctuations. This may indicate that in
      these subjects the corpora lutea have some degree of autonomous regulation.

PMID- 8548057
TI  - No changes of peripheral insulin resistance in polycystic ovary syndrome after
      long-term reduction of endogenous androgens with leuprolide.
AB  - The aim of this study was to investigate the relationship between plasma insulin
      levels, peripheral insulin sensitivity and androgen secretion in ten patients
      with polycystic ovary syndrome and in six obese women as compared with six normal
      weight control subjects. During a euglycemic-hyper-insulinemic clamp no
      significant change of testosterone, androstenedione or dehydroepiandrosterone
      sulfate plasma levels was observed in the two groups of patients or in the
      control subjects; insulin sensitivity was clearly reduced and was similar in
      polycystic ovary patients and in obese women, in spite of the different plasma
      androgen levels. A long-term (5 months) androgen suppression with the
      gonadotropin-releasing hormone agonist leuprolide was not able to improve
      significantly the insulin sensitivity. These results demonstrate that the short
      term hyperinsulinemia achieved with the clamp technique does not affect androgen
      secretion and that insulin resistance, measured with the same technique, is not
      influenced by long-term suppression of plasma androgen levels in polycystic ovary
      syndrome.

PMID- 8548058
TI  - Effect of human galanin on the response of circulating catecholamines to
      hypoglycemia in man.
AB  - Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been
      found in the peripheral and central nervous system, where it often co-exists with
      catecholamines. In order to clarify the possible role of hGAL in the regulation
      of sympathoadrenomedullary function, the effect of a 60-min infusion of hGAL (80
      pmol.kg-1.min-1) on plasma epinephrine and norepinephrine responses to insulin
      induced hypoglycemia in nine healthy subjects was investigated. Human GAL
      administration significantly reduced both the release of basal norepinephrine and
      the response to insulin-induced hypoglycemia, whereas it attenuated the
      epinephrine response by 26%, with the hGAL-induced decrease in epinephrine
      release failing to achieve statistical significance. Human GAL significantly
      increased the heart rate in resting conditions and clearly exaggerated the heart
      rate response to insulin-induced hypoglycemia, whereas it had no effect on the
      blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory
      effect on basal and insulin-induced hypoglycemia-stimulated release of
      norepinephrine. These findings provide further evidence that GAL may modulate
      sympathetic nerve activity in man but that it does not play an important role in
      the regulation of adrenal medullary function.

PMID- 8548059
TI  - Familial dysalbuminemic hyperthyroxinemia in pregnancy.
AB  - A 16-year-old pregnant Puerto Rican woman who had been treated for thyrotoxicosis
      previously was evaluated for goiter, increased total thyroxine (T4) and
      triiodothyronine (T3) and free T4 estimate, despite a normal thyroid-stimulating
      hormone (TSH) concentration. These findings are consistent with a TSH-producing
      pituitary adenoma or the syndrome of generalized thyroid hormone resistance.
      However, sera from the patient, her mother and subsequently her newborn daughter
      demonstrated the increased albumin binding of T4 but not T3 that is
      characteristic of familial dysalbuminemic hyperthyroxinemia (FDH). The free T4
      estimate had been elevated artefactually by the increased affinity of FDH albumin
      for the analog in a one-step assay. The T3 and T4 concentrations were increased
      by pregnancy and T4 was increased further by FDH. This first report of FDH
      recognized during pregnancy emphasizes that the effects of pregnancy on thyroid
      hormone and TSH concentrations complicate the diagnosis of FDH. It is
      particularly important to distinguish this benign condition from thyrotoxicosis
      during pregnancy, because inappropriate treatment may affect fetal development.

PMID- 8548060
TI  - Effects of growth hormone overproduction on grip strength of transgenic mice.
AB  - Growth hormone (GH) is used by athletes like bodybuilders to increase muscle
      strength and weight gain. On the other hand, chronic hypersecretion of GH in
      active acromegaly may result in outwardly hypertrophied but functionally weaker
      muscles. As a model for studying long-term effects of GH on muscle strength, we
      analysed transgenic mice (TM) carrying rat phosphoenolpyruvate carboxykinase
      bovine GH (PEPCKbGH) fusion genes, which are expressed in liver and kidney but
      not in skeletal muscle. Circulating GH levels in TM ranged between 0.5 and 3
      micrograms/ml, resulting in increased (p < 0.001) body weight (wt) as well as
      increased (p < 0.01) weights of forelimb and hindlimb muscles. However, muscle
      weight/body wt ratios of TM were 16-20% smaller than in controls (p < 0.05).
      Forelimb grip strength of hemizygous TM (16 males, 132 +/- 45 days old, body wt =
      56.8 +/- 8.3 g; 32 females, 146 +/- 38 days old, body wt = 54.9 +/- 6.1 g) and
      non-transgenic controls (28 males, 127 +/- 47 days old, body wt = 40.5 +/- 2.9 g;
      33 females, 126 +/- 47 days old, body wt = 32.1 +/- 3.6 g) was determined using
      an automated grip strength meter. Data were computed by analysis of variance,
      taking into account effects of group, sex and age. Least-squares means estimated
      for the grip strength (N) of male TM (1.91) and controls (1.92) were
      significantly (p < 0.05) greater than those of female TM (1.78) and controls
      (1.61). A significant difference between groups was only seen in females (p <
      0.01). Least-squares means estimated for grip strength/body wt ratios (N/10 g) of
      male (0.34) and female TM (0.33) were 29% and 35% lower than those of male (0.48)
      and female controls (0.51), respectively (p < 0.001). In summary, long-term
      elevated GH levels in TM increased muscle weight less efficiently than body
      weight, and muscle strength did not increase proportionally with muscle weight.

PMID- 8548061
TI  - Effects of epidermal growth factor and transforming growth factor alpha on the
      mouse trophoblast outgrowth in vitro.
AB  - In order to analyze the involvement of growth factors in the implantation
      mechanism, we examined the direct effects of epidermal growth factor (EGF) and
      transforming growth factor alpha (TGF-alpha) on trophoblast outgrowth of the
      mouse blastocyst in vitro. ICR mouse blastocysts were cultured for 4 days on a
      culture plate in medium containing EGF or TGF-alpha or conditioned medium
      obtained from cultured endometrial epithelial cells. Blastocysts were also co
      cultured with endometrial epithelial cells. The trophoblast outgrowth of these
      cultured blastocysts was observed daily and the percentage of outgrowing embryos
      was calculated and analyzed statistically by the chi-squared test. Analysis for
      the specific binding of 125I-EGF in outgrown trophoblasts was carried out by
      autoradiography. The co-culture (days 3 and 4) and the presence of EGF (10 ng/ml,
      day 4), TGF-alpha (1 ng/ml, day 3; 10 ng/ml, days 2 and 3; 50 ng/ml, days 2-4) or
      conditioned medium (days 3 and 4) significantly stimulated the rate of
      trophoblast outgrowth. Preincubation of the conditioned medium with monoclonal
      anti-EGF or anti-TGF-alpha antibody suppressed the stimulatory effect of the
      conditioned medium on trophoblast outgrowth. The specific 125I-EGF binding in
      outgrown trophoblasts was demonstrated by autoradiography. These results suggest
      that EGF and TGF-alpha play an important role in the implantation process by
      directly stimulating trophoblast development.

PMID- 8548062
TI  - Angiotensin II modulates steroidogenesis in granulosa and theca in the rabbit
      ovary: its possible involvement in atresia.
AB  - Accumulating evidence has shown the ovary of mammals to contain an intrinsic
      renin-angiotensin system that has been ascribed an autocrine-paracrine role. The
      present study in the female rabbit ovary investigated the putative in vitro
      action of angiotensin II (A II) on basal and gonadotropin-induced
      steroidogenesis. Ovarian follicles from immature female rabbits treated with
      pregnant mare's serum gonadotropin (PMSG) were dissected out and a complete
      separation of the theca interna from the granulosa layer was performed, to
      demonstrate that A II affects separately the two individual cellular components
      of the follicular wall. We could show that theca is a source of estradiol whose
      production under human chorionic gonadotropin (hCG) stimulation was reduced by A
      II. At the same time, A II increased the in vitro hCG-stimulated secretion of
      testosterone by theca. In granulosa, A II decreased hCG-stimulated aromatization
      of androstenedione to estradiol but did not alter the release of hCG-stimulated
      progesterone production. These results suggest that A II could induce locally an
      increase in follicular fluid androgen/estrogen ratio and possibly participate in
      causing atresia.

PMID- 8548063
TI  - Melatonin affects proopiomelanocortin gene expression in the immune organs of the
      rat.
AB  - The induction of opioid peptides derived from cells of the immune system is
      postulated to be the main mechanism involved in the immunomodulatory role of
      melatonin. In this study, it has been demonstrated for the first time that
      melatonin can act on the level of proopiomelanocortin (POMC) gene expression. The
      effect of the pineal hormone, administered in late-afternoon subcutaneous
      injections, was studied in the immune organs of adult male Wistar rats by means
      of a highly sensitive reverse transcription polymerase chain reaction method (RT
      PCR), followed by polyacrylamide gel electrophoresis and densitometric analysis
      of the bands. It was demonstrated that melatonin stimulates the expression of the
      3rd exon of the POMC gene in the lymph nodes and in bone marrow. No significant
      effects of the pineal hormone were observed in the spleen and thymus. The study
      establishes that the formation of short POMC transcripts in the bone marrow and
      lymph nodes may be upregulated by melatonin. Moreover, the pineal hormone exerts
      its effect without antigenic stimulation.

PMID- 8548064
TI  - Advances in the understanding of the molecular basis of obesity.

PMID- 8548065
TI  - Recommendations concerning iodine prophylaxis.

PMID- 8548066
TI  - [The global offensive against AIDS: together for the future (materials of the
      10th International AIDS Congress)].

PMID- 8548068
TI  - The structure of bacterial cell cycle and age structure of bacterial populations.
AB  - Study of synchronous and asynchronous cultures of Bacillus megaterium, Bacillus
      thuringiensis and Bacillus licheniformis has shown that the duration of
      chromosomal DNA replication (period C) is proportional to the generation time,
      and time between two cycles of the DNA replication (known as period I). The
      duration of period C is nearly constant and makes up from 0.5 to 1.0 hour at the
      variations of the generation time from 1.5 to 2.75 hours. The duration of period
      B (the time between the termination of the cell division and initiation of DNA
      replication), and period D (the time between the termination of DNA replication
      and initiation of cell division) were experimentally revealed as stochastic
      parameters. The theoretical model of the bacterial cell cycle and the age
      structure of bacterial population was suggested. The main points of this theory
      are that periods C and I may be stochastically disposed in the division cycle of
      individual cells and a sum of duration of C- and I-periods is equal to generation
      time. The data calculated from the theoretical model were confirmed by the
      experimental data of flow cytofluorometric analysis of the age structure of
      synchronous and asynchronous cultures of the bacilli.

PMID- 8548067
TI  - [Carbohydrate receptors for Mycoplasma fermentans adhesion on human epithelial
      tissues].
AB  - It has been stated that two terminal carbohydrates from polysaccharide complexes
      which are on the surface of human epithelial tissues, namely, alpha-D-glucose and
      N-acetylneuramino acid bound with subterminal galactose via alpha 2-->3-bond
      (NeuAc alpha 2-->3 Gal), may serve receptors for Mycoplasma fermentans adhesion
      on human epithelial cells. M. fermentans shows high selectivity to these
      receptors, though very low affinity. The latter, probably, explains why this
      mycoplasma is able to infect only the limited number of peoples. In the authors'
      opinion people with the lower content of glucose in urine, as well as those who
      suffer from diseases associated with hypothalamo-hypophyseal insufficiency are
      subjected to infection with M. fermentans. People with normal (3.33-5.55 mM) and
      elevated alpha-D-glucose content in blood and in urine are not susceptible to
      this mycoplasma. Results of the research carried have shown that alpha-D-glucose
      solutions of definite concentration may be used to eliminate M. fermentans from
      the urogenital tract of people who have it. The ability of M. fermentans to
      discriminate terminal structure of NeuAc alpha 2-->3 Gal provides it with the
      possibility to adhere human immunodeficiency virus virions on its cells as
      glycoprotein (gp120) of that virus has among its own oligosaccharides certain
      glycopolymers of the similar terminal structure. Then M. fermentans transports
      the virions directly to target cells for this virus. The target cells express
      receptor CD4 glycolized by oligosaccharides of the mentioned terminal structure.
      It provides adhesion of the mycoplasma on the receptor.

PMID- 8548069
TI  - [The effect of the complex probiotic sporolact on the intestinal microbiocenosis
      of warm-blooded animals].
AB  - Complex probiotic sporolact created on the basis of lactobacteria and aerobic
      sporeforming bacteria has been studied for its effect on microflora of the
      gastrointestinal tract of laboratory animals with expressed dysbacteriosis. It
      has been stated that sporolact inhibits pathogenic microorganisms and renewal of
      quantitative characters of obligate representatives of the microbiocenosis of the
      gastrointestinal tract up to the normal level. This complex probiotic has also a
      curing effect on acute gastrointestinal infection of calves induced by pathogenic
      bacteria.

PMID- 8548070
TI  - [The antibiotic resistance of strains of Campylobacter of different origins].
AB  - Antibioticograms of different campylobacteria strains have been analyzed. It is
      shown possible to develop a system of epidemiological marking on this basis. With
      this purpose sensitivity of campylobacteria to gentamycin, canamycin,
      carbenicyllin, tetracylin and erythromycin has been studied. No statistical
      difference in the average markers of resistance in the studied groups of strains
      was observed. This permitted supposing that R-plasmids in "human" strains may be
      isolated not only from the human intestine microflora, but also from other
      sources (animals, birds, environmental objects) as well. There are found common R
      spectra in different groups of strains (Gm Kb Tc Er; Kb and Kb Tc), which
      confirms the same infection source. The study of antibioticograms of
      campylobacteria which circulate among people, animals, birds and environmental
      objects permits revealing regularities of epidemic process in case of
      campylobacteriosis.

PMID- 8548071
TI  - [The use of the immunoperoxidase test with monoclonal antibodies for detecting
      influenza A viruses].
AB  - The immunoperoxidase test was used to detect influenza virus in cells of a
      chorionallanthois shell of infected chicken embryos. Application of monoclonal
      antibodies D8 and A11 in the analysis has permitted detecting reproduction of
      type A (subtypes H1N1, H2N2, H3N2) viruses, the PGA titre of the respective
      allantois liquids being not lower than 1:16. The matrix protein and
      hemagglutinin, detection of which underlies this analysis, were found on the cell
      membrane, in the perinucleus region and as cytoplasmic inclusions.

PMID- 8548072
TI  - [Microbial contamination in a water-treatment system].
AB  - Microorganisms destructors of organic compounds contained in the Kremenchug
      reservoir and water treatment system of heat power station have been
      distinguished and identified. This system does not completely remove microflora
      at all stages of technological process that results in infestation of ion
      exchange resins of the 1st stage filters for water desalting with microorganisms.
      The reasons have been established of the 1st stage desalting filters infestation
      by the reservoir water microflora. It is necessary to form a complex approach to
      solution of the problem of preventing the accident situations: microbe
      infestation of ion-exchange resins of water-desalting filters in the system of
      chemical water treatment of heat power stations.

PMID- 8548073
TI  - [The evaluation of the mutagenic activity of gaseous particles in the atmospheric
      air by using a microbiological test].
AB  - Total mutagen activity of a gas component in chemical pollutions of the
      atmospheric air in a number of industrially developed towns of Ukraine has been
      studied and assessed in a microbiological test on Salmonella typhimurium. The
      towns were chosen proceeding from the specificity of industry: metallurgical
      industry (Mariupol, Zaporozhye, Donetsk, Krivoi Rog, Makeevka); chemical industry
      (Cherkassy, Chernigov; Kremenchug, Severodonetsk, Lisichansk, Gorlovka, Rovno,
      Sumy) and conditionally control ones (Simferopol, Sevastopol, Nikolaev, Poltava,
      Zhitomir). The air samples, 100 m3, have been taken in each town weekly during a
      month by special absorbers of Polysorb-2 type. The extraction of chemical matters
      from absorbers was carried out by traditional methods. Chemical matters were
      dissolved in dimethyl sulphoxide and tested for its ability to induce the gene
      mutations. The studies have shown that the atmospheric air samples from the group
      of "metallurgical" towns prove the mutagen activity, classified as the "middle"
      one (the number of revertant colonies in the experiment exceeded the control 10.3
      to 22.2 times). The mutagenicity of "chemical" towns was on the level of "middle"
      and "weak", that of conditionally control ones was on the level of "weak" only.

PMID- 8548074
TI  - [A complex antibiotic preparation obtained from a medicinal plant from the family
      Asteraceae].
AB  - Data of in vitro and in vivo investigations of antimicrobial activity of
      preparation K carried out both by the authors and by other researchers and
      pharmacological properties of this preparation have been summarized. Preparation
      K has been obtained from medicinal plant of the Asteraceae family. It is a
      natural composition of two antibiotics and of a number of minor compounds. The
      preparation possesses a wide spectrum of biological action. It is antimicrobially
      active against gram-positive bacteria, some species of gram-negative bacteria,
      fungi-dermatophytes including antibiotic-resistant strains. It is not toxic for
      animals, stimulates some defensive reactions of macroorganism, has
      immunomodulating, anti-inflammatory, anti-exudative, keratolytic properties.
      Preparation K is efficient for treatment of experimental mycoses of animals and
      is clinically tested as a local agent for treatment of dermatomycoses.

PMID- 8548075
TI  - Molecular biological bases of resistance to HIV/AIDS (the hypothesis with
      elements of the theory).
AB  - Proceeding from the structure and function of the shell glycoprotein gp120 of the
      human immunodeficiency virus (HIV) and receptor glycoprotein CD4 on target cells
      for this virus, the author assumes that in nature there is genetically determined
      human resistance to the HIV infection and AIDS. This resistance manifests itself
      indirectly via products of the glycosylation system and via the composition and
      order of amino-acid residues in receptor CD4 sites responsible for interaction
      between the receptor and glycoprotein gp120. The author thinks that people in
      whom the glycosylation system determines either B(III) or AB(IV) blood groups are
      potential subjects of the HIV infection. But development of AIDS necessitates
      some conditions more, one of them is susceptibility of the human organism to be
      infected with mollicute Mycoplasma fermentans. This mycoplasma is able to
      recognize terminal NeuAc alpha 2-3 Gal in the composition of oligosaccharides of
      gp120, which permits it to adhere HIV virions on itself and then to transport
      them directly to the cells expressing receptor CD4 and having oligosaccharides of
      the same terminal structure. Oligosaccharides of glycocalyx of the mycoplasma
      protect it from the action of the human immune system and the mycoplasma, having
      "transported" HIV virions to target cells combines with membranes of the latter,
      stimulates formation by them of interleukin-1 and tumour necrosis factor, the
      known effectors of this virus reproduction. On the basis of all these factors the
      author identifies four types of human resistance to HIV/AIDS.

PMID- 8548076
TI  - Adaptation of antihypertensive drug treatment with increasing age: from the young
      to the elderly. Focus on urapidil.

PMID- 8548088
TI  - Is there a better way? Bioethical reflections on palliative cytotoxic drug use.

PMID- 8548089
TI  - Use of nonsteroidal anti-inflammatory drugs in cancer.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in cancer, yet they
      are also responsible for many, often serious, adverse effects. This review
      examines the various mechanisms through which NSAIDs work. It looks at the
      experience built up in using NSAIDs in cancer pain in general, but then
      particularly examines whether the evidence available supports the claim often
      made that these drugs have a specific role in relief of pain from bony
      metastases. Criteria for choosing one NSAID over another, including adverse
      effect profiles, efficacy and tolerability, are considered, as are methods for
      improving the safe use of these drugs.

PMID- 8548090
TI  - Palliative care services: what needs assessment?
AB  - A survey of all district health authorities in England was conducted in order to
      describe current patterns of needs assessment and contract setting for palliative
      care services. Outcome measures included the completion of needs assessments in
      the past five years, the type of data used for needs assessment, and
      recommendations for service development. Copies of contracts for palliative care
      services were requested and analysed according to duration of contract, and audit
      requirements. A 74% response rate was achieved. Over half the health authorities
      had not carried out a needs assessment or service review of palliative care
      services in the past five years. Of those that had undertaken needs assessment,
      about one-quarter were planning more review work, and most of the reports
      expressed the need for more information on many aspects of palliative care.
      Copies of contracts with specialist palliative care providers were supplied by 38
      health authorities, with the majority being of only one year's duration. Although
      conducted within an English context, the study findings have wider implications
      for the process of effective health care purchasing.

PMID- 8548091
TI  - Dying from cancer: results of a national population-based investigation.
AB  - OBJECTIVE: To describe the quality of care received in the last year of life by
      people who die from cancer, focusing particularly on symptom control,
      communication with health professionals, and care in the community. DESIGN:
      Interview survey of family members or others who knew about the last year of life
      of a random sample of people who died in the UK in 1990, based upon methods used
      in nationally representative surveys by Cartwright in 1969, and Cartwright and
      Seale in 1987. SETTING: Twenty district health authorities from a range of inner
      city, outer urban and rural settings. Although self-selected, districts were
      nationally representative in terms of social characteristics and on many
      indicators of health service provision and usage. PARTICIPANTS: Interviews were
      obtained for 2074 cancer deaths out of a random sample of 2915, a 71% response
      rate. MAIN RESULTS: At some stage in the last year of life, 88% were reported to
      have been in pain, 66% were said to have found it to be 'very distressing', and
      61% to have experienced it in their last week. Treatment that only partially
      controlled the pain, if at all, was said to have been received by 47% of those
      treated for pain by their GPs and by 35% of hospital patients. Other common
      symptoms experienced by more than half the sample in their last year were loss of
      appetite, constipation, dry mouth or thirst, vomiting or nausea, breathlessness,
      low mood, and sleeplessness. Half of the respondents (51%) were unable to get all
      the information they wanted about the patient's medical condition when they
      wanted it. Relatives bore the brunt of caring for 81% of the sample. Of
      respondents who had helped to care for the deceased, 65% said that their
      activities had been at least fairly restricted, but 53% had found it rewarding.
      District nurses had helped 60% of the deceased, 20% had had a home help, and 9%
      had received 'meals on wheels'. More help with activities of daily living was
      reported to have been needed by 31%; 24% were reported to have needed more help
      with domestic chores; 25% were reported to have needed more financial help, and
      29% were reported to have needed either more care from district nurses (if had
      some) or some care (if had none). CONCLUSION: There is still some way to go
      before all dying cancer patients receive high quality care. Education in the
      principles of palliative care is needed at all levels of the NHS if high
      standards are to be reached. In addition, adequate resources are required to meet
      the social and health care needs of cancer patients at home. There is, as yet, no
      room for complacency about the care of dying cancer patients.

PMID- 8548092
TI  - Blood transfusion and its benefits in palliative care.
AB  - The value of blood transfusion as a supportive treatment in haematological
      disease and oncology is well established and is seen as an essential part of
      treatment. The place of blood transfusion in the alleviation of symptoms within
      palliative care units is less well established. There has been no evaluation of
      its benefits in terms of symptom relief and impact on the quality of life. This
      study was designed to identify the benefit achieved by transfusion as well as
      possible indicators for its appropriate use in the future. Ninety-seven patients
      were recruited over one year, from the beginning of September 1992 to the end of
      August 1993, from eight centres, all members of the South West Thames Palliative
      Medicine Collaborative Audit Group. Patients completed visual analogue scales
      before and on two occasions after transfusion, to assess its impact on dyspnoea,
      weakness and overall sense of well-being. Results indicated that a significant
      proportion showed improvement in all three parameters. Those whose main
      indication for transfusion was weakness showed a particular benefit. The group of
      patients entered into the study were anaemic in comparison with our normal
      patient population, but the degree of improvement seen did not correlate with the
      degree of anaemia prior to transfusion. We conclude that transfusion does offer
      symptom relief and improvement in well-being in patients with advanced malignant
      disease. It should be considered as a worthwhile option in palliative treatment
      of weakness, dyspnoea and impaired overall sense of well-being, when associated
      with anaemia.

PMID- 8548093
TI  - Epidural diamorphine and bupivacaine stability study.
AB  - Diamorphine and bupivacaine are commonly used together for spinal analgesia,
      although stability data relating to the mixture of the two drugs have not
      actually been established. We therefore performed a stability study using high
      performance liquid chromatography for both drugs and the British Pharmacopoeia
      2,6-dimethylaniline limit test for bupivacaine, over a period of eight days and
      at room temperature. Diamorphine and bupivacaine were combined in various
      concentrations in 100 ml bags for use with the Bard patient controlled analgesia
      pump. We found no significant change in concentration of either drug, and the 2,6
      dimethylaniline limit test was well within set limits. We therefore conclude that
      it is safe to combine these two drugs in this way.

PMID- 8548094
TI  - Interventional radiology in a palliative care setting.
AB  - Interventional radiology is becoming both more common and more complex. It is
      tending to replace many conventional surgical procedures because it is less
      costly and also carries low rates of morbidity and mortality. A minority of
      patients with solid tumours will develop conditions that are amenable to
      improvement with these techniques, especially obstruction of the urinary or
      biliary tracts, or of the oesophagus. This paper describes these procedures, and
      also discusses situations in which this kind of intervention is appropriate. In
      addition to the relief of obstruction of a hollow viscus, various techniques are
      being developed to allow percutaneous tumour ablation; it is likely that these
      will become more widespread in the future.

PMID- 8548095
TI  - Laser therapy in the palliation of dysphagia in oesophageal malignancy.
AB  - Dysphagia is a distressing symptom commonly found in patients with oesophageal
      malignancy. Endoscopic laser therapy, in isolation or in conjunction with other
      treatments, can offer effective palliation. The procedure is outlined together
      with discussion of the advantages and complications of this technique.

PMID- 8548096
TI  - The role of embolization in palliative care.
AB  - Transcatheter arterial embolization (TCAE) is a well recognized radiological
      technique that has been used for over 25 years. It is a method of diminishing
      blood flow through selected vessels by inserting haemostatic material under
      angiographic control. The procedure is performed under local anaesthetic through
      a femoral or, occasionally, an axillary approach. We present our experience of
      the use of TCAE in the management of pain and haemorrhage in three hospice
      inpatients in whom other options had been exhausted. The use of TCAE as a
      technique for the palliation of these symptoms in the hospice setting is
      discussed.

PMID- 8548097
TI  - Case report: confusion responding to dexamethasone in a patient with cancer of
      the prostate.

PMID- 8548098
TI  - A tolerable death.

PMID- 8548099
TI  - Dehydration in dying patients.

PMID- 8548100
TI  - The use of clobazam in uncontrolled epilepsy.

PMID- 8548101
TI  - The method of least squares or the linear model.

PMID- 8548102
TI  - Generalized additive models for medical research.
AB  - This article reviews flexible statistical methods that are useful for
      characterizing the effect of potential prognostic factors on disease endpoints.
      Applications to survival models and binary outcome models are illustrated.

PMID- 8548103
TI  - An introduction to multivariate adaptive regression splines.
AB  - Multivariate Adaptive Regression Splines (MARS) is a method for flexible
      modelling of high dimensional data. The model takes the form of an expansion in
      product spline basis functions, where the number of basis functions as well as
      the parameters associated with each one (product degree and knot locations) are
      automatically determined by the data. This procedure is motivated by recursive
      partitioning (e.g. CART) and shares its ability to capture high order
      interactions. However, it has more power and flexibility to model relationships
      that are nearly additive or involve interactions in at most a few variables, and
      produces continuous models with continuous derivatives. In addition, the model
      can be represented in a form that separately identifies the additive
      contributions and those associated with different multivariable interactions.
      This paper summarizes the basic MARS algorithm, as well as extensions for binary
      response, categorical predictors, nested variables and missing values. It
      presents tips on interpreting the output of the standard FORTRAN implementation
      of MARS, and provides an example of MARS applied to a set of clinical data.

PMID- 8548104
TI  - Extending the elements of tree-structured regression.
AB  - The usage of tree-structured or recursive partitioning methods has grown steadily
      in the decade since the appearance of the definitive monograph 'Classification
      and Regression Trees'. Accompanying this growth have been many methodologic and
      software extensions that have served to give the tree-structured approach even
      wider applicability. This overview highlights some of these developments,
      emphasizing the regression setting. An illustrative example describes how tree
      structured regression, modified to handle right-censored, left-truncated survival
      data with time-dependent covariates, can be used to assess whether rates of
      progression from HIV to AIDS have changed over time.

PMID- 8548105
TI  - Trees and splines in survival analysis.
AB  - During the past few years several nonparametric alternatives to the Cox
      proportional hazards model have appeared in the literature. These methods extend
      techniques that are well known from regression analysis to the analysis of
      censored survival data. In this paper we discuss methods based on (partition)
      trees and (polynomial) splines, analyse two datasets using both Survival Trees
      and HARE, and compare the strengths and weaknesses of the two methods. One of the
      strengths of HARE is that its model fitting procedure has an implicit check for
      proportionality of the underlying hazards model. It also provides an explicit
      model for the conditional hazards function, which makes it very convenient to
      obtain graphical summaries. On the other hand, the tree-based methods
      automatically partition a dataset into groups of cases that are similar in
      survival history. Results obtained by survival trees and HARE are often
      complementary. Trees and splines in survival analysis should provide the data
      analyst with two useful tools when analysing survival data.

PMID- 8548106
TI  - Screening for stratification in two-phase ('two-stage') epidemiological surveys.

PMID- 8548107
TI  - Changing Perspectives in Cardiac Arrhythmia Control: Agents, Techniques, Goals,
      and Outcomes. Symposium proceedings. Dallas, Texas, November 13, 1994.

PMID- 8548108
TI  - Cardiac arrhythmias and antiarrhythmic drugs: recent advances in our
      understanding of mechanism.
AB  - The purpose of this review is to consider our understanding of the mechanisms of
      action of cardiac antiarrhythmic drugs, as well as the status of our
      comprehension of arrhythmias and their therapy. The approach will be to review
      the basis for normal electric activity of the heart, the mechanisms for cardiac
      arrhythmias, and our understanding of the mechanisms of drug action, and to
      distill from these strategies for the future. Immediate strategies in the
      prevention and treatment of life-threatening arrhythmias will most likely
      continue to make use of catheter and electrically based therapy, but the longterm
      treatment of large populations of individuals will still require the search for,
      and testing and administration of, pharmacologic therapy. It is emphasized that
      simplistic approaches to the solution of the complex problem of arrhythmias and
      their management of probably continue to cause problems, and that only by
      mastering the complexities of pathophysiology may success be best assured.

PMID- 8548109
TI  - Contemporary clinical trials in ventricular tachycardia and fibrillation:
      implications of ESVEM, CASCADE, and CASH for clinical management.
AB  - Recent clinical trials in patients with ventricular tachycardia (VT) or
      fibrillation (VF) have occurred in the setting of the disappointing results of
      postinfarction secondary prevention studies using Class I antiarrhythmics (e.g.,
      CAST). ESVEM addressed in a randomized trial whether electrophysiologic study
      (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term
      antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative
      efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia
      recurrence rates were not significantly different by the method of determining an
      efficacy prediction. However, arrhythmia recurrence and mortality were lower (by
      about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III
      agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone
      versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of
      hospital cardiac arrest due to VF. The primary endpoint of cardiac death,
      resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone
      compared with conventional therapy (9% vs 23% at 1 year). An interim report of
      the ongoing CASH study suggested in 230 survivors of cardiac arrest that
      propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1
      year mortality) compared with randomly assigned therapies with amiodarone,
      metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from
      further study. These studies have led to a paradigm shift in the approach to
      antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III
      (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to
      traditional drugs with Class I( conduction slowing) effects, even when guided by
      EPS or HM.

PMID- 8548110
TI  - Expanding indications for the use of Class III agents in patients at high risk
      for sudden death.
AB  - The evidence that antiarrhythmic compounds that act by slowing conduction
      velocity increase mortality in patients with cardiac disease is now compelling.
      Emphasis is now shifting to agents that act by lengthening repolarization and
      have additional antiadrenergic properties. There is preliminary evidence that
      pure Class III agents devoid of antisympathetic activity may also increase rather
      than decrease mortality in certain patients. Thus, in recent years, sotalol and
      amiodarone have emerged as the preferred agents for the control of most
      ventricular arrhythmias occurring in the setting of significant heart disease.
      Sotalol has not been widely studied in postinfarct patients; one trial indicated
      that the drug did reduce total mortality but the difference did not reach
      statistical significance. A number of studies with amiodarone in the
      postmyocardial infarction patients have revealed benefit, but these were from
      nonblinded studies. Two blinded, placebo-controlled studies are currently
      ongoing. A potential new indication of amiodarone is in patients with arrhythmias
      in heart failure in whom amiodarone markedly increased left ventricular ejection
      fraction, with a pronounced suppressant effect on premature ventricular complexes
      and nonsustained ventricular tachycardia and a trend for a decrease in mortality
      in patients with nonischemic cardiomyopathy. The most promising indication of
      amiodarone in low doses is in the maintenance of sinus rhythm in patients with
      atrial flutter and fibrillation. For the present, amiodarone appears to be the
      best prototype of a desirable complex antiarrhythmic compound, if its variegated
      side effect profile can be favorably modified from knowledge of structure
      activity relationships.

PMID- 8548111
TI  - Parenteral antiarrhythmics for life-threatening ventricular arrhythmias.
AB  - The acute management of life-threatening ventricular tachyarrhythmias often
      includes the use of parenteral antiarrhythmics. There are a number of agents
      currently available for this purpose. They are used to suppress inducible
      monomorphic ventricular tachycardia during programmed electrical stimulation,
      they terminate spontaneous sustained ventricular tachycardia, and prevent
      ventricular fibrillation in the setting of an acute myocardial infarction.
      Serious adverse reactions include proarrhythmia, hypotension, severe
      bradyarrhythmias, and precipitation of congestive heart failure. A comparative
      evaluation of intravenous antiarrhythmics is difficult due to inherent
      differences in the choice of agents for study, protocol design, patient
      population, defined endpoint, and serum drug levels. Likewise, the reported
      adverse reaction rates vary from 0.4% to 75%. To understand the difficulties in
      clinical decision-making in this problem area, particularly drug selection, we
      present here a review of pertinent clinical trials evaluating parenteral drug
      efficacy and adverse effects.

PMID- 8548112
TI  - Parenteral antiarrhythmic drug therapy in ventricular tachycardia/ventricular
      fibrillation: evolving role of class III agents--focus on amiodarone.
AB  - More effective intravenous antiarrhythmic agents are required for treatment of
      patients with refractory malignant ventricular arrhythmias. More recently, a
      great deal of interest has been focused on use of intravenous amiodarone for
      these patients. Uncontrolled early studies showed that intravenous amiodarone was
      effective in 42% to 81% of treated patients. Recent large cooperative trials have
      documented the efficacy of intravenous amiodarone in these patients and have
      shown an efficacy comparable to bretylium in patients with refractory sustained
      ventricular tachycardia or fibrillation.

PMID- 8548113
TI  - Proarrhythmia with class III antiarrhythmic drugs: definition, electrophysiologic
      mechanisms, incidence, predisposing factors, and clinical implications.
AB  - Antiarrhythmic drugs can and do induce unexpected and sometimes fatal reactions
      by either producing new symptomatic arrhythmias or by aggravating existing
      arrhythmias. The definition of proarrhythmia has changed since controlled
      clinical studies showed a dichotomy between arrhythmia suppression and mortality.
      The nature of proarrhythmic reactions is linked to the electrophysiologic effects
      of various antiarrhythmic drugs. Whereas Class I agents without accompanying
      effects on repolarization generally produce ventricular tachycardia (often
      incessant) or fibrillation, Class III agents typically produce torsades de
      pointes that may deteriorate into ventricular fibrillation. The precise mechanism
      of torsades de pointes is not fully elucidated, although early after
      depolarization and increases in spatial or temporal dispersion of repolarization
      are likely possibilities. Proarrhythmic risk is lowest for amiodarone and is
      probably related to the drug's complex electrophysiologic profile. The incidence
      of torsades with sotalol increases with dose and the baseline values of the QT
      interval; the incidence with d-sotalol and other pure Class III agents remains
      unclear. Prospective, randomized, placebo-controlled studies to evaluate this are
      under way. The fact that d-sotalol increases mortality in postinfarction patients
      suggests that it may possibly be a common property of most, if not all, pure
      Class III compounds. The ongoing clinical trials with various Class III agents
      are likely to provide the critical information on this important therapeutic
      issue.

PMID- 8548114
TI  - Drugs versus devices: contemporary practice in light of contemporary trials.
AB  - In years past, the secondary prevention of life-threatening ventricular
      arrhythmias was limited to empiric drug therapy. In close temporal proximity to
      the birth of electrophysiologic study-guided treatment strategies to manage these
      arrhythmias, devices to convert arrhythmias were envisioned and designed. Now,
      advanced generation implantable defibrillators provide synchronized, low-energy
      cardioversion, antitachycardia pacing, and pacing support for bradycardia. Over
      the past decade and half, this technology that was once applied as a therapy of
      last resort has evolved and emerged as a therapy of first choice. Recently,
      however, enthusiasm for drug treatment strategies has also increased, especially
      the use of amiodarone. Most experts now agree that drug therapy chosen by
      electrophysiologic study guidance provides superior survival compared to the
      empiric use of Class I drugs, as long as a drug that suppresses arrhythmia
      inducibility is found. The empiric use of amiodarone and beta blockers may also
      improve outcome. This review examines some of the recent clinical trials
      utilizing pharmacologic and nonpharmacologic methods. The importance of ongoing
      and future clinical trials is emphasized.

PMID- 8548115
TI  - Ventricular tachycardia after myocardial infarction: from arrhythmia surgery to
      catheter ablation.
AB  - Ventricular tachycardia due to prior myocardial infarction is caused by reentry.
      Intraoperative mapping at the time of arrhythmia surgery has shown that the
      reentry circuits are diverse in size and location. Many circuits are large,
      extending over several square centimeters. Endocardial excision guided by
      activation sequence mapping, fractionated sinus rhythm electrograms, or visual
      identification of scarred subendocardium renders 69% to 95% of patients free from
      inducible ventricular tachycardia, but with an operative mortality that exceeds
      8% at most centers. Catheter ablation is difficult due to limitations of catheter
      mapping, relatively small size of lesions produced with current techniques, and
      limited access to intramural and epicardial portions of the reentry circuits.
      Many problems need to be overcome for catheter ablation to achieve success
      comparable to that of surgery. At present, only hemodynamically tolerated
      ventricular tachycardias can be mapped. Progress is being made, and it is likely
      that catheter ablation will become a viable therapy for subgroups of patients
      with postmyocardial infarction ventricular tachycardia.

PMID- 8548116
TI  - Catheter ablation for the treatment of paroxysmal supraventricular tachycardia.
AB  - Radiofrequency catheter ablation has evolved into a front-line curative therapy
      for patients who have paroxysmal supraventricular tachycardia secondary to Wolff
      Parkinson-White syndrome. AV nodal reentrant tachycardia, and atrial tachycardia.
      In patients with accessory pathways, cure rates exceed 90% in almost all anatomic
      locations. Equally high success rates are noted in patients with atriofascicular
      pathways and the permanent form of junctional reciprocating tachycardia.
      Complications secondary to catheter ablation of accessory pathways occur in 1% to
      3% of patients and include cardiac perforation, tamponade, AV block, and stroke.
      In patients with AV modal reentrant tachycardia, selective slow pathway ablation
      is curative in over 95% of patients with a very low risk of AV block. Atrial
      tachycardias originating in both the left and right atria can be successfully
      ablated in over 80% of patients. Given the overall effectiveness of this
      procedure, radiofrequency catheter ablation should be considered as front-line
      therapy in patients with recurrent or drug-refractory paroxysmal supraventricular
      tachycardia. Although an effective therapy, the risks and benefits of this
      procedure need to be assessed in all patients who are candidates for this
      procedure.

PMID- 8548117
TI  - Atrial fibrillation and flutter: maintaining stability of sinus rhythm versus
      ventricular rate control.
AB  - Two major treatment strategies have emerged for managing atrial fibrillation:
      maintaining sinus rhythm by chronic administration of suppressive antiarrhythmic
      agents versus controlling the ventricular rate and chronic anticoagulation.
      Potential benefits of maintenance of sinus rhythm include improvement of the
      hemodynamic profile of the patient, a decreased risk of cerebrovascular
      accidents, reduced symptoms, and, if atrial fibrillation is successfully
      suppressed, possible elimination of the need for the chronic anticoagulation.
      When selecting long-term antiarrhythmic drug therapy for suppression of atrial
      fibrillation, it should be recalled that at least 50% of patients have a
      recurrence of the arrhythmia within the first year and the majority of other
      patients have a recurrence within the next 3 to 5 years. In addition, the risk of
      proarrhythmia and sudden cardiac death must be considered; this has stimulated
      interest in nonpharmacologic approaches to maintaining sinus rhythm. Large
      multicenter randomized trials are now under way to compare the benefits and risks
      of maintaining sinus rhythm versus controlling the ventricular rate and
      chronically anticoagulating patients in atrial fibrillation. Important endpoints
      of these trials include mortality, functional capacity, and quality of life.

PMID- 8548118
TI  - Nonpharmacologic approaches to the treatment of atrial fibrillation and atrial
      flutter.
AB  - The high prevalence of atrial fibrillation, the associated morbidity and
      mortality, the absence of safe and effective drug therapy, and an increased
      understanding of the pathophysiologic basis of atrial fibrillation and flutter
      have collectively led to the development of novel nonpharmacologic treatments for
      the management of these arrhythmias, including the CORRIDOR and MAZE surgical
      procedures, catheter-based ablation and modification of AV conduction, catheter
      based ablation of atrial flutter and fibrillation, and internal atrial
      defibrillation. These surgical and catheter-based techniques offer potentially
      curative therapy while sparing the long-term risk of antiarrhythmic drug therapy.
      For patients with typical atrial flutter, catheter ablation affords to cure rate
      in excess of 70%. As technological innovations further facilitate identification
      and ablation of the critical isthmus in the floor of the right atrium, success
      rates should improve substantially. For patients with atrial fibrillation, AV
      junction ablation with implantation of a rate-responsive ventricular pacemaker
      should be considered palliative therapy, as should modification of AV junction
      conduction. The MAZE procedure offers very high cure rates, but because it
      currently involves open heart surgery, patient selection is critical. Catheter
      based procedures emulating aspects of the MAZE procedure may one day offer cure
      rates comparable to those of the surgery itself, but additional research and
      technological development are necessary to further define and refine the minimal
      effective procedure, and then to facilitate the placement of contiguous, full
      thickness lesions in precise three-dimensional configurations. In the interim,
      the implantable automatic atrial defibrillator may offer a means for rapidly
      restoring sinus rhythm without the risks of long-term antiarrhythmic drug
      therapy.

PMID- 8548119
TI  - Lipomatous tumours of soft tissues: an update.
AB  - This review summarizes the clinicopathological features of recently characterized
      variants of lipomatous tumours of soft tissue, attempts to deal with some
      difficult conceptual issues relating to adipocytic neoplasms and aims to provide
      an update on cytogenetic aspects of fatty tumours. Myolipoma is a rare benign
      neoplasm, occurring most frequently in adults in the deep soft tissue of the
      abdomen or retroperitoneum, and is composed of irregularly admixed mature adipose
      and smooth muscle tissues. Chondroid lipoma represents an unusual benign lesion
      occurring mainly in adult females subcutaneously or in deep soft tissue; it is
      easily mistaken for myxoid liposarcoma or extraskeletal myxoid chondrosarcoma.
      Spindle-cell liposarcoma is a variant of well-differentiated liposarcoma quite
      commonly found in subcutaneous tissue of the shoulder region and upper limbs and
      is composed of relatively bland-appearing spindle cells mixed with a well
      differentiated liposarcomatous component. Recently there has been considerable
      debate about classification of lipomatous tumours. The term atypical lipoma was
      proposed for a group of well-differentiated non-metastasizing liposarcomas
      arising in surgically amenable soft tissues and for deep-seated atypical
      adipocytic neoplasms that show variation in adipocytic size and atypical stromal
      cells but lack lipoblasts. However, these neoplasms recur repeatedly and may
      dedifferentiate and thereby acquire metastatic potential. We use the diagnosis
      atypical lipoma with caution and propose to use the terms well-differentiated
      liposarcoma and atypical lipoma interchangeably. The relationship between myxoid
      and round-cell liposarcoma, which constitutes the morphological spectrum of a
      single entity, has been clarified but there remain considerable problems in
      defining likely clinical behaviour. The recent advances in cytogenetic
      characterization and classification of lipomatous tumours, which is already
      proving to be of diagnostic importance, are reviewed, and the genetic importance
      of the distinct chromosomal translocation in myxoid/round cell liposarcoma is
      briefly discussed.

PMID- 8548120
TI  - Distribution of thrombospondin and integrin alpha V in DCIS, invasive ductal and
      lobular human breast carcinomas. Analysis by electron microscopy.
AB  - The ultrastructural distribution of thrombospondin (TSP) and its cell surface
      receptor, integrin alpha V, was studied in two cases of human breast carcinoma:
      one of ductal carcinoma in situ (DCIS) with an invasive component, and one of
      invasive lobular carcinoma. In DCIS, moderate immunolabelling for TSP and
      integrin alpha V was observed in the rough endoplasmic reticulum and at the
      plasma membrane of intraductal carcinoma cells. TSP was also associated with
      extracellular matrix collagen fibrils surrounding in situ carcinoma cells. In the
      invasive part of this ductal carcinoma, most of the malignant cells were negative
      for TSP, while integrin alpha V was moderately expressed in these cells. In sharp
      contrast, typical strands of invasive lobular carcinoma cells in "Indian file"
      showed moderate TSP immunostaining in the rough endoplasmic reticulum and strong
      immunoreactivity for TSP at the plasma membrane and in the extracellular matrix.
      Moderate to strong immunoreactivity for integrin alpha V was also observed in
      invasive lobular carcinoma cells. Because of the role of TSP during cancer cell
      invasion, the different expression patterns of TSP in invasive ductal versus
      lobular carcinoma may well reflect biological differences between these two types
      of breast carcinoma and could account for the peculiar diffuse invasive behaviour
      of breast lobular carcinoma cells.

PMID- 8548121
TI  - Trisomy 1 and 8 occur frequently in hepatocellular carcinoma but not in liver
      cell adenoma and focal nodular hyperplasia. A fluorescence in situ hybridization
      study.
AB  - Conventional cytogenetic studies revealed gains and structural aberrations of
      chromosome 1 to be the most consistent chromosomal aberrations in hepatocellular
      carcinoma (HCC). We investigated touch preparations of eight HCC, five
      cholangiocellular carcinomas (CCC), five liver cell adenomas (LCA), four focal
      nodular hyperplasias (FNH) as well as nine specimens of normal liver tissue using
      fluorescence in situ hybridization (FISH) with centromere specific probes for
      chromosomes 1 and 8. Polysomies of chromosome 1, especially trisomy 1, were found
      in five of eight HCC and four of five CCC but in no normal liver tissue or benign
      tumour. Only three of seven cases of HCC revealed trisomy 8 whereas the five
      benign liver tumours and all normal liver tissues examined had disomy 8. Our
      results confirm conventional cytogenetic findings in terms of chromosome 1
      aberrations in HCC although they are not specific for these types of malignant
      liver tumours. Since alpha-satellite probes were used in our study, only gains or
      losses including the centromeric regions of the chromosomes 1 and 8 could be
      detected. Nevertheless, our findings suggest that FISH may help in the
      differential diagnosis of malignant versus benign neoplasms of the liver.

PMID- 8548122
TI  - Multiple occurrence of borderline hepatocellular nodules in human cirrhotic
      livers: possible multicentric origin of hepatocellular carcinoma.
AB  - Borderline hepatocellular nodules (BHN), atypical adenomatous hyperplasia,
      macroregenerative nodule type II or dysplastic nodules in the cirrhotic liver are
      considered to be important prcancerous lesions transforming to hepatocellular
      carcinoma (HCC). In order to evaluate the uni- or multicentric origin of BHN and
      HCC arising from BN, we surveyed 30 cirrhotic livers with BHNs that had been
      surgically resected or autopsied during 1973-1993. Among the 30 cirrhotic livers
      with BHNs, two or more BHNs were present in a single cirrhotic liver in 10 (33%)
      cases, while only one BHN was present in a single cirrhotic liver in the
      remaining 20 (67%) cases. The mean number of BHN in a cirrhotic liver with
      multiple BHNs was 3.5. Carcinomatous foci were present within BHN in 6 (60%) of
      the 10 cirrhotic livers with multiple BHNs, while they were present in 4 (20%) of
      the 20 cirrhotic livers with a single BHN; this difference was statistically
      significant (P < 0.05). Coexistance of HCC was noted in 8 (80%) of the 10
      cirrhotic livers with multiple BHNs, and in 3 (15%) of the 20 cirrhotic livers
      with a single BHN; this difference was statistically significant (P < 0.01).
      There were no significant differences in age, sex, aetiology and morphology
      between cirrhotic livers with multiple BHNs and those with a single BHN. These
      data suggest that BHN and HCC arising from BHN may be of multicentric origin.

PMID- 8548124
TI  - Basic fibroblast growth factor-heparan sulphate complex in the human dialysis
      related amyloidosis.
AB  - A major constituent of the amyloid fibrils in dialysis-related amyloidosis is
      beta 2-microglobulin (beta 2-MG). Heparan sulphates (HS) co-localize with the
      amyloid fibrils and monocytes/macrophages are commonly found around amyloid
      deposits, but the role of HS in amyloidogenesis is not yet defined. HS have
      variable saccharide sequences and can interact specifically with basic fibroblast
      growth factor (bFGF), a potent chemotactic factor for the monocyte/macrophage.
      The present investigation was undertaken to look for a functional link between co
      localized HS and the pathogenesis of dialysis-related amyloidosis. Using amyloid
      enriched ligament, immunohistochemical localization was tested for beta 2-MG,
      endogenous bFGF, and bFGF-binding portions of HS. For the detection of bFGF
      binding portions of HS, the ligament sections were incubated with exogenous bFGF
      and then with anti-bFGF antibody. The specificity of the interaction between bFGF
      and HS was established by confirming a concomitant loss of immunoreactivity
      during selective removal of HS with heparitinase. beta 2-MG, endogenous bFGF, and
      bFGF-binding portions of HS were detected between bundles of collagen. Endogenous
      bFGF and bFGF-binding portions of HS were not detected in more advanced amyloid
      lesions, whereas beta 2-MG and other portions of HS were detected. We propose
      that beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS form a complex
      and localize in the early amyloid lesions of dialysis-related amyloidosis.

PMID- 8548123
TI  - Fibrosing vasculitis in Wegener's granulomatosis: ultrastructural and
      immunohistochemical analysis of the vascular lesions.
AB  - This study of two cases of pulmonary Wegener's granulomatosis (WG) focuses on the
      ultrastructural aspects of the vascular wall injury and on the
      immunohistochemical characterization of the perivascular connective matrix. The
      iterative waves of endothelial cell necrosis and regeneration are demonstrated by
      the multilamellar appearance of the basal lamina. Neutrophils infiltrate the
      vessel wall and myofibroblasts are recruited to injured vessels. The perivascular
      connective matrix associates basement-membrane like and fibrillar material with
      fibrin deposits. The initiation of the fibrosing process was assessed by the
      visualization of matrix molecules involved in targeting (p-fibronectin),
      organizing (cellular fibronectin and tenascin) and stabilizing (lysyl-oxidase)
      the fibrogenic activity. These elementary lesions affect different levels of the
      vascular tree, and capillaritis is involved in the extension of the pathological
      process. Lysyl-oxidase labelling reveals the fibrosing front which is located on
      the border of dense fibrosis. The markers of fibrosing activity disappear in the
      areas of fibrosis following vasculitis and/or ischaemic necrosis and/or
      granulomatosis. Vasculitis plays a major role in both the genesis and progression
      of the fibrosis observed in the late stage of WG.

PMID- 8548125
TI  - Immunohistochemical analysis of rat and human respiratory cilia with anti-dynein
      antibody: comparison between normal cilia and pathological cilia in primary
      ciliary dyskinesia.
AB  - Wistar Imamichi rat and human respiratory cilia were examined with anti-dynein
      antibody (AD2), which is specific for sea urchin sperm flagellar dynein. AD2
      labelled fresh-frozen normal rat and human cilia stained clearly by
      immunofluorescence and the peroxidase-antiperoxidase (PAP) technique. On
      immunoelectron microscopy, AD2 labelled the outer dynein arms of normal human
      cilia. Paraffin-embedded normal human cilia also stained by immunofluorescence,
      although not always clearly. Neither the cilia of WIC-Hyd male rats, an animal
      model of Kartagener's syndrome, nor human cilia from patients with primary
      ciliary dyskinesia (PCD) reacted positively by the immunofluorescence or PAP
      technique. Western blots of normal rat cilia yielded a single band of about 450
      kDa. In conclusion, AD2 recognizes the outer arm dynein heavy chains of healthy
      cilia and may be useful in diagnosing and classifying PCD light microscopically
      especially when only paraffin-embedded specimens are available. This approach may
      be of potential use for better defining and classifying PCD.

PMID- 8548126
TI  - Improved detection of medically important fungi by immunoperoxidase staining with
      polyclonal antibodies.
AB  - This study was performed to identify pathological fungi of eight species
      [Aspergillus fumigatus, Candida albicans, Torulopsis (Candida) glabrata,
      Cryptococcus neoformans, Fusarium anthophilum, Rhizopus oryzae, Sporothrix
      schenckii and Trichosporon beigelii] in formalin-fixed, paraffin-embedded tissue
      sections by indirect immunoperoxidase staining. Mature albino rabbits were
      immunized with formalin-killed organisms. Antibodies were prepared by
      precipitation. Immunoperoxidase staining was applied to the paraffin-embedded
      tissue sections of experimentally infected mice and human autopsy and surgical
      specimens. Although the cell walls of each fungus stained clearly, many cross
      reactivities appeared. However, it was possible to obtain specificity for the
      eight species by absorption and dilution of the antisera.

PMID- 8548127
TI  - Ultrastructure and immunoreactivity of dystrophic axons indicate a different
      pathogenesis of Hallervorden-Spatz disease and infantile neuroaxonal dystrophy.
AB  - An immunohistochemical and ultrastructural analysis of dystrophic axons (DAs) in
      the brain and peripheral nerve of a patient with familial infantile neuroaxonal
      dystrophy (INAD) and in the brain of a patient with familial Hallervorden-Spatz
      Disease (HSD) revealed prevalent membrano-tubular or granulo-vesicular profiles
      with a graded pattern of evolution in INAD, while dense bodies, vesicles and
      amorphous material were present in HSD. DAs immunoreactivity with tai-protein and
      200 kDa-neurofilament antibodies was stronger in HSD than in INAD. In both cases
      immunohistochemistry was positive for ubiquitin and negative for beta-tubulin and
      beta-amyloid. Distinct ultrastructural features and immunoreactivity pattern of
      cytoskeletal components suggest different pathogenetic mechanisms.

PMID- 8548128
TI  - Extensive pulmonary haemorrhage in an Egyptian mummy.
AB  - We report on the morphological and trace element findings of several internal
      organs from an Egyptian mummy approximately dating from the year 950 B.C.
      according to 14C-analysis. By use of a multidisciplinary approach we succeeded in
      discovering evidence for severe and presumably recurrent pulmonary bleeding
      during life. This was suggested by the finding of massive haemosiderin deposits
      in the lung and a selectively and markedly elevated level of iron in trace
      element analysis of the lung tissue. Furthermore, we observed an enhanced
      deposition of birefringent particles in the lung tissue, without significant
      fibrosis. The histological analysis of liver, stomach and intestine confirmed the
      macroscopic organ diagnoses without evidence of any major pathological processes.
      In addition, analysis for various drugs revealed a significant deposition of
      tetrahydrocannabinol (THC), nicotine and cocaine in several organs of the mummy.
      The concentration profiles additionally provide evidence for a preferential
      inhalation of THC, while nicotine and cocaine containing drugs seem to have been
      consumed orally.

PMID- 8548129
TI  - Immunoreactivity for p53 and mdm2 and the detection of p53 mutations in human
      malignant mesothelioma.
AB  - Previous immunohistochemical studies on malignant mesothelioma with antibodies
      recognizing both the wild and the mutant types of the p53 protein have shown
      immunoreactivity in 25-70% of cases. This study was designed to determine whether
      there is immunoreactivity for p53 and mdm2 protein in malignant mesothelioma and
      to correlate p53 expression with the detection of mutations in p53 at DNA level.
      In 10 of 15 cases there was immunoreactivity for p53. In 6 of these cases
      immunoreactivity for mdm2 was also detected. In one p53-immunonegative case, a
      mutation of the p53 gene resulting in a stop codon was found. These results
      suggest that mdm2 might be involved in the inhibition of p53 in malignant
      mesothelioma. Also, these data suggest the existence of other proteins than mdm2
      that may associate with p53.

PMID- 8548130
TI  - Histamine-stimulated production of matrix metalloproteinase 1 by human rheumatoid
      synovial fibroblasts is mediated by histamine H1-receptors.
AB  - The purpose of this study was to investigate the role of histamine in human
      rheumatoid synovial fibroblasts in the production of factors responsible for
      tissue remodelling and cartilage breakdown in rheumatoid arthritis. We examined
      the effects of histamine of tritiated thymidine incorporation, production of
      matrix metalloproteinase-1 (MMP-1), histamine H1-receptor expression,
      phosphoinositide metabolism and intracellular calcium ion concentration ([Ca2+]i)
      in human rheumatoid synovial fibroblasts. Tritiated thymidine incorporation
      studies demonstrated that histamine markedly stimulated the proliferation of
      rheumatoid synovial fibroblasts. Immunofluorescence and Northern blot analyses
      revealed that proMMP-1 production was also stimulated by histamine. The levels of
      inositol phosphates and [Ca2+]i in the cells were elevated in response to
      histamine, indicating that the cells expressed histamine H1-receptors; and
      Northern blot analysis indicated that these H1-receptors were up-regulated by
      histamine. In in situ hybridization, large amounts of histamine H1-receptor mRNA
      were also detected in rheumatoid synovial tissue. These results suggest that the
      interaction between H1-receptor expression in rheumatoid synovial fibroblasts and
      histamine secretion by mast cells and macrophages in the affected sites is an
      important event responsible for tissue remodelling and joint destruction in
      rheumatoid arthritis.

PMID- 8548131
TI  - Simultaneous gastric adenocarcinoma and MALT-type lymphoma in Helicobacter pylori
      infection.
AB  - A 79-year-old women with upper abdominal pain, vomiting and weight loss was found
      at endoscopy to have a large tumour mass in the gastric body. Histology of
      forceps biopsies revealed an adenocarcinoma of intestinal type. Gastrectomy was
      performed, but extensive lymph node metastasis precluded a curative surgical
      approach. Histopathological study of the specimen, however, revealed two distict
      malignancies, which arose in the setting of Helicobacter pylori-associated
      chronic gastritis with partial mucosal atrophy. One tumour was a gastric
      carcinoma, while the other was a primary B-cell lymphoma of the stomach (CD20
      positive). The lymphoma comprised both a low-grade component (mucosa-associated
      lymphoid tissue- or MALT-type lymphoma), and a high-grade component (large cell
      lymphoma with CD30-positive giant cells). Infection with H. pylori was confirmed
      by the serological presence of IgG antibodies to H. pylori-antigens, including
      antibodies against the 128 kDa protein of the cytotoxin-associated gene (cagA
      gene) of H. pylori.

PMID- 8548132
TI  - Combined choriocarcinoma, hepatoid adenocarcinoma, small cell carcinoma and
      tubular adenocarcinoma in the oesophagus.
AB  - We describe an oesophageal tumour composed of choriocarcinoma, hepatoid
      adenocarcinoma, small cell carcinoma and tubular adenocarcinoma. The
      choriocarcinomatous areas and hepatoid adenocarcinomatous areas contained beta
      human chorionic gonadotropin-positive cells and alpha fetoprotein-positive cells,
      respectively. The small cell carcinomatous areas contained cells positive for
      serotonin or adrenocorticotrophic hormone, while the tubular adenocarcinomatous
      areas contained cells positive for carcinoembryonic antigen. Non-neoplastic
      gastric type columnar epithelium was found directly adjoing the tumour at the
      oral side. This tumour, with its unprecedented histology combination of tissues
      may have originated in Barrett's oesophagus, although we could not confirm a
      history of chronic gastro-oesophageal reflux.

PMID- 8548133
TI  - Myolipoma of the round ligament: report of a case with a review of the English
      literature.
AB  - Tumours consisting of a mixture of mature adipose and smooth muscle tissues,
      including those designated lipoleiomyomas, fibrolipoleiomyomas and myolipomas,
      are exceedingly rare, but most often occur in the uterine corpus. We describe
      here a case of such a tumour arising in the right round ligament of a 44-year-old
      woman. The tumour, which measured approximately 20x15x10 cm, was well
      encapsulated and did not involve the intrapelvic organs. Intricate mixtures of
      adult adipose tissue and bland smooth muscle exhibited no cellular atypia or
      nuclear mitotic figures, and there was little vascular proliferation. We
      diagnosed the lesion as a myolipoma of soft tissue with dual differentiation, and
      have found only 13 cases of this tumour including our own in the English
      literature. The present tumour is the first reported in the round ligament.
      Although this tumour is rare, its recognition is important for the avoidance of
      erroneous diagnoses.

PMID- 8548135
TI  - Innovative approaches in symptom management.

PMID- 8548134
TI  - The relationship between aneuploidy and p53 overexpression during genesis of
      colorectal adenocarcinoma.

PMID- 8548136
TI  - Wider issues in pain management.
AB  - In this paper the accepted holistic approach to pain management in cancer care is
      scrutinized. A series of oppositions are considered to result from the essential
      indeterminate nature of pain, and that pain is fundamentally lived and
      experienced in the body. These oppositions are discussed in terms of mind-body
      dualism and embodiment, and in particular the body as subject and object. The
      discussion is illustrated with examples from research examining individual
      expressions of pain. Patients' powerful attempts to manipulate subject-object
      distinctions in recounting their experience of pain is offered as a means by
      which patients make sense of their pain, and connect it to their bodies and to
      their identity. The implications of acknowledging personal and cultural meanings
      attributed to pain are highlighted, with recommendations for future research and
      clinical practice initiatives.

PMID- 8548137
TI  - 'Just grin and bear it and hope that it will go away': coping with urinary
      symptoms from pelvic radiotherapy.
AB  - Fifty per cent of patients with cancer are treated with radiotherapy during the
      course of their disease. Although side-effects have been described in studies,
      these are often not representative of the impact that these symptoms have on the
      individual. This article explores one area of radiotherapy management, that of
      pelvic radiotherapy in men, and describes how symptoms that patients experience
      during and following treatment can be a debilitating outcome of cancer therapy.
      At present, there is limited knowledge on how best to prevent symptoms from
      occurring, who is most at risk and how to manage these symptoms. Technology has
      advanced with accelerated regimes, conformal planning and new radiotherapy
      treatments. Yet still we are no further forward in dealing with toxicity from
      treatment. The focus of research has been on developing new cures and only now
      are questions being raised about the quality of life of patients having
      radiotherapy treatment.

PMID- 8548138
TI  - Menopause: a problem for breast cancer patients.
AB  - Many women who are treated for breast cancer will subsequently undergo the
      menopause, either as a result of cancer treatment or as a natural process. For
      this group of women hormone replacement therapy is currently not recommended and
      so women lose a major option to help control menopausal symptoms. The extent of
      this problem has not been widely researched and alternative methods of coping
      with menopause in this group have not been explored. This paper reviews the
      menopause in relation to these women and suggests avenues for future research.

PMID- 8548139
TI  - Oral problems in advanced cancer.
AB  - Despite the unquestionable relevance of ensuring effective oral care for patients
      with advanced cancer, inadequate research activity has been directed towards
      developing and evaluating specific mouth care regimes for this group of seriously
      ill patients. The prevalence of the problems experienced by these individuals is
      well known and ensures that we have a clear picture of the areas where practice
      development is urgently needed. This paper presents a critique of research-based
      oral care interventions through a consideration of the management of the
      following problems: coated mouth and tongue; dry mouth; infection (fungal, viral,
      bacterial); pain; altered taste. Where possible, research findings are presented,
      but for many of the areas of care it is possible only to offer guidelines based
      upon an understanding of the normal structure and function of the oral cavity,
      the agents and tools currently in use, and practice-based evidence. There is an
      urgent need for a coordinated body of research activity within this field.

PMID- 8548140
TI  - New strategies for the management of malignant ascites.
AB  - Intractable malignant ascites accounts for 6% of all hospice admissions. The
      onset of malignant ascites indicates a poor prognosis, hence minimal supportive
      therapy is indicated. This paper examines the method of control for malignant
      ascites presently available to patients, examines their limitations and proposes
      new strategies for managing intractable malignant ascites. Ascites is discussed
      in terms of its pathology--that is, as a form of lymphoedema. With this in mind
      treatment is proposed based upon principles incorporated into lymphoedema
      management. Nurses have taken a dominant role in the care of patients with
      lymphoedema and there appears no reason why ascites management cannot become the
      remit of nurses offering appropriate, but predominantly palliative therapy.

PMID- 8548141
TI  - Nursing as therapy in the management of breathlessness in lung cancer.
AB  - Breathlessness has been described as an unpleasant sensation, but if it
      encompasses suffering, as some argue, it is much more than this. Breathlessness
      is also a major issue for people with cancer. Much of the effort to manage
      breathlessness has thus far focused on the treatment of underlying causes or on
      pharmacological strategies. In this paper, broader rehabilitative goals of care
      and treatment for breathlessness in lung cancer are addressed. Breathing control
      techniques have been developed to help patients with non-malignant disease to
      avoid breathlessness at rest or on exertion. A study is described (Corner et al.,
      1995) which evaluated the effectiveness of breathing retraining and psychosocial
      support for breathlessness in lung cancer. Breathlessness can be a frightening
      and powerful experience. It can symbolize a threat to life itself. In these
      circumstances, the goal of therapy is to alleviate loss of function and to ease
      the psychological burden that so restricts the individual. An 'integrative' model
      of breathlessness is discussed, in which the emotional experience of
      breathlessness is considered inseparable from the sensory experience and the
      biological mechanisms. Evidence is presented from a small study of the
      experiences of nurses working in the experimental clinic for breathlessness which
      suggests that the emotional consequences of breathlessness have a profound
      influence on how it is managed in practice. Finally, it is argued that symptoms
      are sometimes generalized too much. Experience is particular, not universal, and
      an open, accepting and therapeutic approach to managing illness has to be
      involved with messy and sometimes frightening emotions.

PMID- 8548142
TI  - Education for cancer nurses: a European priority.

PMID- 8548143
TI  - Effectiveness of nursing.

PMID- 8548144
TI  - Health care contracts in Britain and the United States: a case for technology
      transfer?
AB  - One unexpected point of convergence between the British and North American health
      care systems is the increased use of negotiated contracts to govern relationships
      between purchasers and providers. In Britain, the internal market reforms
      introduced a special regime of National Health Service (NHS) contracts; in the
      United States there has been a move from disorganization towards integration with
      the emergence of larger purchasing coalitions and provider organizations. While,
      in the past, US patients were simply billed for services or assigned claims to
      the provider, it is now common for payment to be made directly from purchaser to
      provider and for the terms of these transactions to be set out in contracts. This
      paper draws on the reading of contracts, interviews with contracting parties, and
      ongoing research on NHS contracting in Wales to compare contracting practice
      within the two systems. It examines how the very different environments of the
      public, hierarchically-regulated NHS and the private health care market of the US
      influence the detailed content of contract clauses. The analysis passes over
      similarities, different solutions to common problems, and fundamental differences
      of approach, before considering the possibilities for transfers of contracting
      'technology'.

PMID- 8548145
TI  - Customer complaints in the National Health Service.
AB  - This paper addresses the role of consumer complaints in the flourishing quality
      assurance industry within the National Health Service (NHS), and considers the
      traditional ethos of complaints within the service. The advent of the internal
      market is considered as one of a range of factors which may change attitudes of
      NHS staff to complaints. In evaluating how complaints services might develop
      relevant literature is reviewed and recent national data on complaints procedures
      are cited.

PMID- 8548146
TI  - The value of nursing.

PMID- 8548147
TI  - Sense of coherence among elderly somatic patients: predictive power regarding
      future needs of care.
AB  - The main aim was to study the predictive power of sense of coherence regarding
      future needs of care among elderly patients evaluated as medically ready for
      discharge from somatic emergency care. A secondary aim was to study the
      consistency of sense of coherence over time among patients with this kind of
      experience. The sample consisted of 53 Swedish patients (mean age 82.8 years, SD
      = 6.6 years) who had completed their medical treatment at surgical or orthopaedic
      departments. The predominant diagnosis was lower limb fractures. Sense of
      coherence was assessed twice, on the day the patient was evaluated as medically
      ready for discharge and 1 month later. On the second assessment occasion, 28
      patients had returned to their homes, 17 were staying at institutions, and eight
      had died. Patients who returned to their homes reported the strongest sense of
      coherence while still in hospital. Patients who were staying at institutions
      scored lowest on the overall sense of coherence scale and on the
      comprehensibility subscale. Patients who died before the second measurement
      occasion scored lowest on the meaningfulness subscale. A correlation of 0.51 was
      noted between the two assessments of sense of coherence, indicating a moderate
      temporal consistency.

PMID- 8548148
TI  - Research challenges: issues in the management of research projects.
AB  - Earlier work published in this journal has highlighted problems in the management
      of nursing research, including tensions between nurse managers and researchers.
      Building on this earlier work the challenges posed by research in the volatile
      organizational context of the British National Health Service (NHS) are discussed
      in relation to two areas: the early stages of establishing a research project,
      and defining the roles and responsibilities of those involved in the research. It
      is argued that many of the problems which hinder the successful completion of
      research can be traced back to the early stages of establishing the project,
      including a lack of clarity about its aims, purpose and objectives. Such problems
      are compounded by the lack of attention given to the task of defining the
      respective roles and responsibilities of manager and researcher, as well as of
      others in a research team. It is concluded that one of the major tasks for
      research and development in the current climate of the NHS is to find ways of
      dealing with such challenges which promote increased understanding between
      manager and researcher. Ways in which this might be achieved are suggested.

PMID- 8548149
TI  - Training needs analysis. Necessity or luxury?
AB  - With the plethora of offerings in post-registration education available to nurses
      it is at times difficult for individual nurses to identify their current and
      future needs, and more so to go about meeting those needs through a logical
      educational or career progression. Nursing and its relationship with other health
      care professionals is also changing rapidly, and post-registration education, in
      order to keep abreast of the changes has to evaluate its effectiveness and move
      forward with programmes of study which actually meet the changing need of nurse
      practitioners within the society they serve. This article attempts to highlight
      the importance of needs analysis when considering programme planning in the
      changing climate of post-registration nurse education.

PMID- 8548150
TI  - Mainly nursing-led clinical guidelines--behavioural outcomes.

PMID- 8548151
TI  - Internal mammary vessels: anatomical and clinical considerations.
AB  - This study was designed to investigate the anatomy of the internal mammary
      (thoracic) artery (IMA) and comitant vein(s) (IMV) relevant to their use in
      microsurgery. We dissected the internal mammary (thoracic) vessels bilaterally in
      86 cadavers from the clavicle down to the 6th rib. At the level of the 4th rib,
      the distance between the sternum and the IMA was large enough [range 10.0-23.6
      mm] and the diameter of the IMA [range 0.99-2.55 mm] and comitant vein(s) [range
      0.64-4.45 mm] wide enough for both end-to-end and/or end-to-side anastomosis.
      These results were in close agreement with supplementary measurements obtained by
      Doppler ultrasound in 34 healthy female volunteers. Based on all these findings
      we suggest that the internal mammary vessels are suitable recipient vessels for
      free tissue transfers in the thoracic region, especially for breast
      reconstruction with the free transverse rectus abdominis myocutaneous (TRAM)
      flap.

PMID- 8548152
TI  - Internal mammary vessels: a reliable recipient system for free flaps in breast
      reconstruction.
AB  - In breast reconstruction with a free flap following mastectomy, the recipient
      vessels most widely used are in the axillary system, which limits flap movement
      and flexibility in breast shaping. In addition, scarring and fibrosis can make
      dissection of the vessels difficult. We have performed 22 breast reconstructions
      using a free transverse rectus abdominis myocutaneous (TRAM) flap anastomosed to
      the internal mammary (thoracic) vessels. There has been no flap failure. The
      surgical techniques and the advantages and limitations of the internal mammary
      system are presented and the internal mammary vessels compared with the axillary
      vessels as a recipient vascular system.

PMID- 8548153
TI  - Anatomy of the internal mammary veins and their use in free TRAM flap breast
      reconstruction.
AB  - The anatomy of 61 internal mammary veins (IMV) in the 3rd, 4th and 5th
      intercostal spaces was studied in 34 fresh human cadavers by injection and
      corrosion methods and surgical dissection. The IMV was present in all 34
      cadavers. Four different patterns of venous anatomy were identified: Types 1
      (69%) and 2 (26%) were common, Types 3 (3%) and 4(2%) were rare. The most common
      arrangement (Type 1) consists of the internal mammary vein running medial and
      parallel to the artery to the 4th intercostal space where it divides into the
      medial and the lateral IMV, the lateral crossing the internal mammary artery
      (IMA) anterior to it in direction from medial to lateral. Both veins are
      connected by interconnecting branches. The mean diameter of internal mammary
      veins is 2.7 mm (range 1.1-4.8 mm) for the medial and 1.8 mm (range 0.5-3.5 mm)
      for the lateral one. The mean distance from the lateral bordoffof the sternum of
      the medial vein is 9 mm (range 2-18 mm) and 14 mm (range 9-24 mm) for the lateral
      vepfpff. We present a review of 7 patients in whom internal mammary vessels were
      used as recipient vessels for breast reconstruction with free TRAM flaps with no
      complications, as well as the advantages and disadvantages of such a procedure.

PMID- 8548154
TI  - Free flaps in the management of intrathoracic sepsis.
AB  - Experience with 5 free flaps, 1 TRAM and 4 latissimus dorsi flaps, transferred
      intrathoracically for the management of chronic sepsis is described. Healing and
      elimination of sepsis was achieved in all cases despite the infection being
      resistant to all previous more traditional forms of treatment including
      thoracoplasty. The results were achieved with minimal morbidity and argue for the
      early consideration of free flaps in the management of chronic intrathoracic
      sepsis in appropriate circumstances. A review of the limited available literature
      concerning this topic is presented.

PMID- 8548155
TI  - Evaluation of the laser scanner as a surface measuring tool and its accuracy
      compared with direct facial anthropometric measurements.
AB  - The development of new laser scanning techniques enabling the capture of 3-D
      images which can be quantitatively assessed permits their use for surface
      measurements of the face. We used a laser optical surface scanner to study 30
      subjects and took 83 facial anthropometric measurements, using 41 identifiable
      landmarks on the scanned image. These were compared to the standard
      anthropometric measurements using the same landmarks. Of these, 12 (14.0%) showed
      a mean difference less than 1.0 mm and were considered highly reliable
      measurements and 16 (19.0%) with less than 1.5 mm difference were considered
      reliable. The highly reliable measurements were mainly in the nasal and
      circumoral regions and the landmarks involved were mainly those in the mid
      saggital plane. This indicates that the laser scanner can be a useful tool for
      rapid facial measurements in selected anatomical parts of the face. Accurate
      location of landmarks and operator skill are important factors to achieve
      reliable results.

PMID- 8548156
TI  - Intraoral reconstruction using a second free flap for recurrent or metachronous
      carcinoma.
AB  - A retrospective review of clinical records at Canniesburn Hospital has identified
      6 patients in whom intraoral squamous carcinomas were excised and reconstruction
      performed by free tissue transfer on two separate occasions. The interval between
      procedures ranged from 8 months to 8 years. One dorsalis pedis flap was used and
      the other tissue transfers were radial forearm free flaps, two of which were
      osteocutaneous. One flap completely failed and the rest survived. There was no
      evidence of greater risk in carrying out a second microsurgical intraoral
      reconstruction in this series. 4 out of 6 patients remain alive following their
      second procedure, one after 9 years. The results suggest that in selected cases
      it may be worthwhile to carry out a major intraoral reconstruction on more than
      one occasion.

PMID- 8548157
TI  - Perineural spread of cutaneous squamous cell carcinoma manifesting as ptosis and
      ophthalmoplegia (orbital apex syndrome).
AB  - This paper reports two cases of orbital apex syndrome. The most salient clinical
      signs, ophthalmoplegia and eyelid ptosis, arose from perineural spread of facial
      squamous cell carcinomas that were previously excised with tumour-free surgical
      margins and exhibited no signs of local or other regional recurrence. The
      interest of these two cases lies in the fairly rare occurrence of this type of
      tumour spread and the highly aggressive nature of the tumour, unequivocal
      diagnosis of which usually arrives too late for a surgical solution. Awareness of
      the possibility of such perineural spread may allow the clinician to establish an
      early diagnosis and thus undertake radical surgery, thereby increasing the
      likelihood of success in combination with postoperative radiotherapy.

PMID- 8548158
TI  - Cheek reconstruction with an expanded prefabricated musculocutaneous free flap:
      case report.
AB  - We present a case of reconstruction of the left cheek with a prefabricated
      musculocutaneous flap. A pedicled serratus anterior muscle flap was transferred
      to the left chest, deep to skin. The muscle flap and overlying skin were
      expanded. The expanded, prefabricated musculocutaneous flap was then transferred
      as a free flap to the left cheek defect.

PMID- 8548159
TI  - Immediate and delayed breast reconstruction with permanent tissue expanders.
AB  - Breast reconstruction has greatly advanced during the past decade, offering the
      surgeon and the patient a choice between autologous tissue transfer and silicone
      implants, as well as between immediate and delayed reconstruction. In this
      retrospective study we reviewed the results of immediate versus delayed
      reconstruction with a permanent tissue expander, a method which is simple, fast
      and gives good aesthetic results. 19 patients had immediate reconstruction and 25
      patients had delayed reconstruction. Capsular contracture (Baker II, III, IV) was
      more common with delayed (7/25) than immediate (3/19) reconstruction; however,
      the difference was not statistically significant (p = 0.47). The overall
      complication rates and the final aesthetic results were similar in the two
      groups.

PMID- 8548160
TI  - Is soft tissue expansion in lower limb reconstruction a legitimate option?
AB  - From 1986 to 1994, a consecutive series of 34 patients had 37 expanders placed in
      their legs. Indications for expansion included removal of painful ro unstable
      scars, chronic post-traumatic ulcers and one benign skin lesion. In 13 patients
      the lesion or scar was greater than 5 cm in diameter. The area of expansion was
      mainly in the proximal and distal thirds of the lower limb. On three occasions
      two expanders were simultaneously used in the same patient. The treatment with
      this technique was ultimately successful in 23 patients (67.6%) but 15 of the 23
      patients (44% of the 34 patients) had minor wound healing problems. Before 1990,
      technical complications such as leaking injection ports caused further small
      interventions in 6 patients without compromising the ultimate outcome. The goal
      was not achieved with the expansion technique in 11 patients (32%). 5 of these 11
      patients could be treated successfully with another surgical modality. All 34
      patients were re-evaluated with an average follow-up of 4.5 years. We conclude
      that tissue expansion is ideal for removal of localised areas of scar, repair of
      contour defects and excision of benign tumours. Contraindications of soft tissue
      expansion are, in general, extensive scarred areas with compromised blood supply
      after trauma, vascular disease and osteomyelitis. These conditions require
      reconstruction with well vascularised tissue such as muscle flaps. A compliant
      patient is essential for lower limb reconstruction with tissue expansion. In
      spite of the tempting simple method of tissue expansion, success in the lower
      limb depends not only on the indication but also on the operating technique of
      the plastic surgeon.

PMID- 8548161
TI  - The effect of hyperbaric oxygen on different phases of healing of ischaemic flap
      wounds and incisional wounds in skin.
AB  - Several studies have revealed a positive effect of treatment of ischaemic wounds
      and flaps with hyperbaric oxygen. We studied the effect of 100% oxygen (2.4 ATA)
      for 90 min daily on different phases of healing ischaemic and normal incisional
      wounds in rats. Hyperbaric oxygen on day 0-3 significantly increased almost all
      the force parameters of ischaemic flap wounds by 41-57% after 10 days of healing.
      On the other hand, when the treatment was continued until day 9 the positive
      effect on the wound healing was abolished. Furthermore, when hyperbaric oxygen
      was given on days 4-9 there was a tendency towards a decrease in the
      biomechanical parameters. Hyperbaric oxygen had no effect on the healing of
      normal incisional wounds.

PMID- 8548162
TI  - Oxidative processes and free radical scavengers in ischaemia-reperfusion injury
      in adipocutaneous flaps: in vitro lipid peroxidation assessment.
AB  - An in vitro lipid peroxidation study measuring Schiff base and TBAR formation in
      homogenates of the fat and skin fractions of epigastric free flaps of DA-rats was
      performed to determine the role of oxygen-derived free radicals (ODFRs) in the
      aetiology of ischaemic injury and of ischaemia and reperfusion injury following
      cold (0-1 degree C) storage. The storage intervals were 0, 48, 72, 96 and 120 h
      in the study on ischaemic injury and 72 and 96 h in the study on combined
      ischaemia and reperfusion injury. Reperfusion was accomplished by anastomosing
      the pedicle vessels of the flap to the femoral vessels of a recipient; the
      reperfusion period was 15 min. In addition to a control group (C), three
      experimental groups were created to test the benefit of a preischaemic single
      passage perfusion with a hypertonic citrate solution (HCA), a pre- and
      postischaemic treatment with desferrioxamine (DFX) and a pre- and postischaemic
      treatment with lipoic acid (LA). The susceptibility of homogenates of skin and
      fat fractions of epigastric free flaps in DA-rats for lipid peroxidation
      increased significantly whenever the cold (0-1 degree C) ischaemic interval was
      prolonged from 0 to 72 h. These findings offer circumstantial evidence for the
      role of ODFRs in the aetiology of ischaemic injury. Following a short reperfusion
      period after extended periods of cold (0-1 degree C) ischaemia, no significant
      increase in susceptibility for lipid peroxidation could be found. Furthermore, no
      unequivocal role in the prevention of ischaemia and/or reperfusion injury by the
      use of either HCA, or DFX or LA could be found. The exact role of ODFRs in the
      aetiology of ischaemia-reperfusion injury in this setting remains unclear.

PMID- 8548163
TI  - Lateral cutaneous nerve of the thigh blockade as primary anaesthesia for
      harvesting skin grafts.
AB  - The lateral cutaneous nerve of the thigh (LCNT) supplies a large area of skin in
      an ideal site for harvesting a split skin graft. LCNT block was used as primary
      local anaesthesia for harvesting split skin grafts in 23 patients with a variety
      of injuries. Their ages ranged from 26 to 99 years. The mean age was 69 years.
      The onset of full anaesthesia took between 15 and 20 min. The area anaesthetised
      ranged from 250 cm2 to 1020 cm2 with a mean of 569 cm2. There were 17 successful
      blocks and 6 failures. Most of the 6 failures occurred during the early phase of
      the study. We have found that, with experience, LCNT block is a safe, simple and
      reliable method for achieving adequate anaesthesia for harvesting split skin
      graft from the thigh and that it provided excellent postoperative analgesia.

PMID- 8548164
TI  - A mirror image of the first and second branchial arch syndrome associated with
      cleft lip and palate in monozygotic twins.
AB  - A rare case of monozygotic twins revealing a mirror image of the first and second
      branchial arch syndrome with accessory ear and hemifacial microsomia, associated
      with unilateral cleft lip and palate, is presented. Although the concordance
      and/or discordance rate of monozygotic or dizygotic twins with cleft lip and
      palate is well reported, that of twinning of the first and second branchial arch
      syndrome has been very rarely described. First and second branchial arch syndrome
      occurs sporadically but cleft lip and palate are strongly related to the
      influence of environmental factors with a considerable hereditary tendency. The
      study of twinning of congenital anomalies is important in the investigation of
      the pathogenesis of genetic and environmental effects. The twins were diagnosed
      as monozygotic with almost complete certainty by ABO blood typing, HLA typing,
      finger prints, and DNA typing. Concordance was noticed, which suggests a
      hereditary tendency. Since concordance in these monozygotic twins was exhibited
      by a precise mirror image of first and second branchial arch syndrome, spinal
      scoliosis and cleft lip and palate, it is possible that an environmental factor
      induced these complex anomalies.

PMID- 8548165
TI  - A simple device for use as a mammastat, scalp or finger tourniquet.

PMID- 8548166
TI  - Breast reduction and breast cancer.

PMID- 8548167
TI  - Regulation of muscle glycogen metabolism by CGRP and amylin: CGRP receptors not
      involved.
AB  - The aim of the present study was to determine whether amylin and calcitonin gene
      related peptide (CGRP) act through shared or distinct receptors to inhibit
      insulin-stimulated incorporation of [14C]-glucose into glycogen. Rat amylin was 3
      fold more potent than either rat alpha CGRP or rat beta CGRP at reducing glycogen
      synthesis from [14C]-glucose in insulin-treated rat soleus muscle. This action
      was blocked by peptide antagonists, with the rank order of potency being AC187 >
      salmon calcitonin8-32 (sCT8-32) > h-alpha CGRP8-37 for antagonism of either
      amylin or CGRP. The antagonist potency order correlated with affinity for amylin
      receptors measured in rat nucleus accumbens but not CGRP receptors measured in
      rat L6 muscle cells. Inhibition of glucose incorporation into glycogen by amylin
      and CGRP appears to be mediated by shared receptors that have the pharmacological
      characteristics of amylin receptors, and are distinct from previously described
      CGRP receptors.

PMID- 8548168
TI  - Release of endothelium-derived hyperpolarizing factor (EDHF) by M3 receptor
      stimulation in guinea-pig coronary artery.
AB  - 1. The muscarinic receptor subtype(s) involved in the release of endothelium
      derived hyperpolarizing factor (EDHF) were studied in the guinea-pig coronary
      artery by recording the membrane potential in the smooth muscle cells with
      intracellular microelectrodes. 2. Acetylcholine (ACh, pD2 6.68) was 10 times more
      potent than the M2 agonist, oxotremorine (pD2 5.65) and 500 fold more potent than
      the M1 agonist, McN-A-343 (pD2 3.95) in evoking the EDHF hyperpolarization. 3.
      The M3 muscarinic antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodide (4
      DAMP) was the most potent (pA2 9.5) in inhibiting the release of EDHF evoked by
      ACh, being more potent than pirenzepine (pA2 6.7), and AFDX-116 (pA2 6.1) which
      preferentially block M1 and M2 receptors, respectively. 4. These results suggest
      that EDHF is released from the endothelium of the guinea-pig coronary artery upon
      the activation of the muscarinic M3 receptor subtype.

PMID- 8548169
TI  - Comparative effects of activation of soluble and particulate guanylyl cyclase on
      cyclic GMP elevation and relaxation of bovine tracheal smooth muscle.
AB  - 1. The effects of nitric oxide-donating compounds and atrial natriuretic peptide
      on cyclic GMP accumulation and mechanical tone were compared with the effects of
      isoprenaline in bovine tracheal smooth muscle. 2. Sodium nitroprusside, glyceryl
      trinitrate, S-nitroso-N-acetylpenicillamine (SNAP), atrial natriuretic peptide
      and isoprenaline each caused concentration-dependent inhibitions of histamine
      maintained tone (EC50 values 320 +/- 80, 150 +/- 45, 14,000 +/- 4,000, 2.8 +/-
      0.8 and 6.6 +/- 4.3 nM respectively). 3. When compared with their effects on
      histamine-induced tone, sodium nitroprusside was equally potent and effective in
      causing relaxation of methacholine-supported tone (EC50 290 +/- 90 nM) while
      isoprenaline was as effective, but less potent (EC50 30 +/- 7 nM). SNAP was more
      potent and equi-effective as a relaxant of methacholine-supported tone (EC50 340
      +/- 140 nM). At the maximum concentrations of glyceryl trinitrate and atrial
      natriuretic peptide tested against methacholine-supported tone, relaxations of
      52% and 14% of the isoprenaline maximum were seen. 4. Sodium nitroprusside,
      glyceryl trinitrate and atrial natriuretic peptide each induced concentration
      dependent increases in cyclic GMP accumulation. The time-courses of accumulation
      correlated closely with the relaxant actions of these compounds. 5. Pretreatment
      of tracheal smooth muscle with sodium nitroprusside or SNAP caused a rightward
      shift of the concentration-effect curve for histamine while reducing the maximum
      response. 6. LY 83583, a putative guanylyl cyclase inhibitor, caused a
      concentration-dependent reduction in basal cyclic GMP accumulation in tracheal
      smooth muscle and inhibited the effects of sodium nitroprusside on cyclic GMP
      accumulation. 7. LY 83583 also inhibited the relaxation of histamine-supported
      tone by glyceryl trinitrate, sodium nitroprusside, SNAP and atrial natriuretic
      peptide, and also sodium nitroprusside- and SNAP-induced relaxation of
      methacholine-supported tone. However, it had no significant effect on glyceryl
      trinitrate-induced relaxation of methacholine-supported tone. 8. It is concluded
      that the relaxant actions of sodium nitroprusside, glyceryl trinitrate, SNAP and
      atrial natriuretic peptide follow as a result of their ability to activate either
      soluble or particulate guanylyl cyclase leading to cyclic GMP accumulation.
      Although there does not seem to be any functional difference in the relaxant
      response to cyclic GMP generated by the particulate as opposed to soluble form(s)
      of guanylyl cyclase, atrial natriuretic peptide receptor/guanylyl cyclase
      activation was much less effective in causing relaxation of methacholine
      supported tone when compared to activators of soluble guanylyl cyclase.

PMID- 8548170
TI  - Effect of frusemide, ethacrynic acid and indanyloxyacetic acid on spontaneous Ca
      activated currents in rabbit portal vein smooth muscle cells.
AB  - 1. The effect of frusemide, ethacrynic acid and indanyloxyacetic acid was
      investigated on spontaneous calcium-activated chloride (ICl(Ca)) and potassium
      currents (IK(Ca)) in rabbit portal vein cells with the perforated patch
      technique. 2. Frusemide (0.3-1.0 x 10(-3) M) reduced the amplitude of spontaneous
      transient inward chloride currents (STICs) in a concentration-dependent manner.
      The degree of inhibition on STIC amplitude was similar between -50 and +30 mV and
      frusemide did not alter the STIC reversal potential (Erev). 3. The voltage
      dependent exponential decay of STICs, which is thought to represent closure of
      chloride channels, was not altered by frusemide. 4. The amplitude and frequency
      of spontaneous potassium outward currents (STOCs) were not altered by frusemide.
      Since both STICs and STOCs are activated by calcium released from intracellular
      stores these data indicate that frusemide may block directly ICl(Ca). 5.
      Ethacrynic acid (2-5 x 10(-4) M) decreased the amplitude of STICs in a
      concentration-dependent manner by a similar amount at potentials of -50 to +30 mV
      but did not alter the STIC Erev. However, these concentrations of ethacrynic acid
      also reduced STOC amplitude and 5 x 10(-4) M ethacrynic acid evoked a sustained
      outward current in most cells at 0 mV; thus ethacrynic acid has a more complex
      action than simple block of ICl(Ca). 6. Indanyloxyacetic acid reduced both STIC
      amplitude and decay time without affecting STOCs and thus also seems to inhibit
      directly ICl(Ca). It is discussed whether block of ICl(Ca) mediates the
      vasodilator effect of these agents.

PMID- 8548171
TI  - Functional characterization of the adenosine receptor mediating inhibition of
      peristalsis in the rat jejunum.
AB  - 1. The non-selective adenosine agonist, 5'-N-ethylcarboxamidoadenosine (NECA), is
      a potent inhibitor of morphine withdrawal diarrhoea in rats. More recently we
      found that NECA exerts its antidiarrhoeal effect by inhibiting secretion in both
      the jejunum and ileum and also by inhibiting peristalsis in the ileum. The
      specific aim of this study was to characterize the receptor in the rat jejunum
      mediating inhibition of peristalsis via functional studies using a range of
      metabolically stable adenosine analogues based on the pharmacological criteria of
      relative agonist and antagonist potencies. 2. Peristalsis in the rat isolated
      jejunum was achieved by raising the pressure to between 7-11 cmH2O for 3 min
      followed by a 3 min rest period (pressure at zero). The mean rate of peristalsis
      during inflation was 7.3 +/- 0.1 peristaltic waves per 3 min and this rate
      remained consistent for up to 30 min, in 5 separate tissues. The inhibitory
      effects of the adenosine analogues were quantified by expressing their effects as
      a % reduction in the mean number of peristaltic contractions derived from the
      control tissues. 3. The rank order of agonist potency to reduce the rate of
      peristalsis was: N6-cyclopentyladenosine (CPA) > NECA > R(-)-N6-(2
      phenylisopropyl)adenosine (R-PIA) > chloroadenosine (2-CADO) > S-PIA > 2
      phenylaminoadenosine (CV-1808). This order complies well with the rank order of
      agonist potency that represents the activation of the A1 receptor subtype (CPA >
      R-PIA = CHA = > NECA > 2-CADO > S-PIA > CV-1808). 4. The selective A1 adenosine
      antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and the nonselective
      adenosine antagonist 8-phenyltheophylline (8-PT) at their respective
      concentrations of 10 nM and 2 microM caused parallel rightward shifts in the
      concentration-response curve to the non-selective Al/A2 agonist NECA. DPCPX was
      significantly more potent at inhibiting NECA than 8-PT as revealed by their
      apparent pA2 values; DPCPX (9.5) and 8-PT (7.26). The high affinity of DPCPX
      relative to that of 8-PT suggests the presence of an Al and not an A2B receptor.
      In addition, the high affinity of DPCPX(pA2:9.37) against the selective Al
      agonist CPA, further confirms the presence of the Al receptor subtype.5. In this
      study we found that the Al adenosine receptor is involved in regulating in vitro
      peristalsis which is different from the adenosine receptor regulating inhibition
      of secretion (A2B) in the same region of intestine of the same species. We
      propose that A2B adenosine agonists could be of clinical value in the management
      of diarrhoea that is due to microbiological organisms where antimotility effects
      are not desired.

PMID- 8548172
TI  - Extended concentration-response curves used to reflect full agonist efficacies
      and receptor occupancy-response coupling ranges.
AB  - 1. An approach is described for generating extended agonist concentration
      response curves where the responses are unconstrained by the normal tissue
      maximum response. Functional antagonism is employed to hold the tissue state in
      the range where any change in stimulus can be translated into a measurable
      response. 2. The maximum response of these extended concentration-response curves
      provides an index of intrinsic activity reflecting the agonist efficacy and the
      receptor occupancy-response coupling range. 3. The use of this approach is
      illustrated with extended concentration-response curves for noradrenaline (NA),
      vasopressin, acetylcholine (ACh), and 5-methylfurmethide in the small mesenteric
      and tail arteries of the rat. Both NA and vasopressin can maximally activate the
      arteries, but the new protocol shows that NA can produce more cellular activation
      than vasopressin in the tail artery. Both ACh and 5-methylfurmethide are full
      agonists but ACh has a higher intrinsic activity than 5-methylfurmethide. The ACh
      muscarinic receptors in the mesenteric artery have a larger occupancy-response
      range than the ACh muscarinic-receptors in the tail artery, and the alpha
      adrenoceptors in the tail artery appear to have a larger occupancy-response
      coupling range than those in the mesenteric artery. 4. This approach extends our
      ability to compare the efficacies of full agonists, and to compare the occupancy
      response coupling ranges of receptors that can normally maximally activate the
      assay tissue. This is achieved without the use of an irreversible antagonist and
      should be applicable to many receptors and pharmacological assay systems where
      responses are stable and functional antagonists are available.

PMID- 8548173
TI  - A role for endothelin in bicuculline-induced neurogenic pulmonary oedema in rats.
AB  - 1. The possible contribution of endogenous endothelin (ET) to the pathogenesis of
      seizure-associated pulmonary oedema was examined in mechanically ventilated rats
      after intravenous bolus injection of the gamma-aminobutyric acid (GABA)
      antagonist, bicuculline (1.2 mg kg-1). 2. Recurrent seizure activity elicited by
      bicuculline injection led to rapidly developing pulmonary oedema. Within 4 min
      after bicuculline application (1.2 mg kg-1), arterial O2 partial pressure (PaO2)
      significantly dropped from 17.49 +/- 1.20 kPa to 7.51 +/- 2.21 kPa (P < 0.01) and
      arterial CO2 partial pressure (PaCO2) significantly increased from 4.64 +/- 0.56
      kPa to 8.15 +/- 0.99 kPa (P < 0.01). Gradually a progressive acidosis developed.
      Moreover, mean arterial blood pressure (MABP) and end-inspiratory airway pressure
      (Paw) rapidly increased. 3. Concomitantly there was a time-dependent increase of
      big ET-1 and ET-1 levels in bronchoalveolar lavage (BAL) as determined by
      combined reverse phase high performance liquid chromatography (h.p.l.c.) and
      radioimmunoassay. BAL levels of both peptides increased up to 8 min after
      bicuculline injection and slowly decreased subsequently. In contrast, BAL from
      animals injected with vehicle did not contain detectable amounts of ET. 4.
      Pretreatment with the endothelin-converting enzyme inhibitor, phosphoramidon (5.4
      mg kg-1, i.v.) for 5 min significantly (P < 0.001) reduced peak ET-1 levels in
      BAL fluid by 65.4 +/- 9.9% at 8 min after bicuculline injection. Simultaneously
      it afforded protection from hypoxia. PaCO2 did not increase and PaO2 decreased
      only slightly from 14.63 +/- 1.00 kPa to 12.97 +/- 0.61 kPa (P > 0.05) after
      phosphoramidon pretreatment. In contrast, vehicle-treated animals that received
      bicuculline showed both significant hypercapnia as well as profound hypoxia.
      Phosphoramidon significantly diminished the maximum increase in Paw by 76.7 +/-
      12.4% (P <0.005), but only slightly affected the MABP. Phosphoramidon
      pretreatment had no effect on the acidosis.5. Pretreatment with the ETA receptor
      antagonist, BQ-123 (1 mg kg-1, i.v.), for 5 min did not affect the levels of ET-1
      in the BAL fluid at 8 min after bicuculline injection but did ameliorate the
      development of hypoxia. No hypercapnia developed and Pa02 decreased only
      moderately from 16.65 +/-0.25 kPa to 14.19 +/-2.15 kPa (P>0.05) in BQ-123-treated
      animals. In contrast, vehicle-treated animals that received bicuculline exhibited
      significant hypercapnia as well as profound hypoxia. BQ-123 significantly reduced
      the increase in Paw by 51.3 +/- 12.8% (P < 0.01). It affected MABP only slightly
      and had no effect on the acidosis.6. These results suggest that ET peptides play
      a significant role in this model of neurogenic pulmonary oedema and may act as
      mediators of respiratory distress. The deleterious effects of endogenous ET in
      this model are primarily mediated via the ETA receptor, for they were inhibited
      by the ETA receptor antagonist, BQ-123. ETA receptor antagonists may therefore be
      of potential therapeutic value in respiratory distress.

PMID- 8548174
TI  - D-cycloserine transport in human intestinal epithelial (Caco-2) cells: mediation
      by a H(+)-coupled amino acid transporter.
AB  - 1. The ability of D-cycloserine to act as a substrate for H+/amino acid symport
      has been tested in epithelial layers of Caco-2 human intestinal cells. 2. In
      Na(+)-free media with the apical bathing media held at pH 6.0, D-cycloserine (20
      mM) is an effective inhibitor of net transepithelial transport (Jnet) of L
      alanine (100 microM) and its accumulation (across the apical membrane) in a
      similar manner to amino acid substrates (L-alanine, beta-alanine, L-proline and
      glycine). In contrast L-valine was ineffective as an inhibitor for H+/amino acid
      symport. Both inhibition of L-alanine Jnet and its accumulation by D-cycloserine
      were dose-dependent, maximal inhibition being achieved by 5-10 mM. 3. Both D
      cycloserine and known substrates for H+/amino acid symport stimulated an inward
      short circuit current (Isc) when voltage-clamped monolayers of Caco-2 epithelia,
      mounted in Ussing chambers, were exposed to apical substrate in Na(+)-free media,
      with apical pH held at 6.0. The D-cycloserine dependent increase in Isc was dose
      dependent with an apparent Km = 15.8 +/- 2.0 (mean +/- s.e. mean) mM, and Vmax =
      373 +/- 21 nmol cm-2h-1. 4. D-Cycloserine (20 mM) induced a prompt acidification
      of Caco-2 cell cytosol when superfused at the apical surface in both Na+ and
      Na(+)-free conditions. Cytosolic acidification in response to D-cycloserine was
      dependent upon superfusate pH, being attenuated at pH 8 and enhanced in acidic
      media. 5. The increment in Isc with 20 mM D-cycloserine was non-additive with
      other amino acid substrates for H+/amino acid symport.

PMID- 8548175
TI  - Evidence that [3H]-alpha,beta-methylene ATP may label an endothelial-derived cell
      line 5'-nucleotidase with high affinity.
AB  - 1. In membranes prepared from a permanent cell line of endothelial origin (WEC
      cells), [3H]-alpha, beta-methylene ATP ([3H]-alpha, beta-meATP) labelled high
      (pKd = 9.5; Bmax = 3.75 pmol mg-1 protein) and low (pKd = 7.2; Bmax = 23.3 pmol
      mg-1 protein) affinity binding sites. The high affinity [3H]-alpha, beta-meATP
      binding sites in the WEC cell membranes could be selectively labelled with a low
      concentration of the radioligand (1 nM). In competition studies performed at a
      radioligand concentration of 1 nM, 88.6% of the sites possessed high affinity
      (pIC50 = 8.26) for alpha, beta-meATP. 2. The high affinity [3H]-alpha, beta-meATP
      binding sites appeared heterogeneous since in competition studies a number of
      nucleotide analogues (alpha, beta-meADP, ATP, ADP, AMP, GTP, GppNHp, GMP) and
      adenosine identified two populations of the sites labelled by 1 nM [3H]-alpha,
      beta-meATP. The proportion of sites with high affinity for these compounds was
      found to vary between 42 and 69%. 3. Approximately 60-69% of the binding sites
      labelled with 1 nM [3H]-alpha, beta-meATP possessed high affinity for alpha, beta
      meADP (pIC50 = 8.87), AMP (pIC50 = 7.12), GMP (pIC50 = 7.34), UTP (pIC50 = 6.12),
      GTP (pIC50 = 7.59), GppNHp (pIC50 = 7.35) and adenosine (pIC50 = 5.45). The sites
      at which these compounds possessed high affinity were probably the same, since,
      in the presence of GMP at a concentration (10 microM) sufficient to inhibit
      selectively the binding of [3H]-alpha,beta-meATP, the [3H]-alpha,beta-meATP
      binding sites with high affinity for AMP, UTP, alpha, beta-meADP, GTP, GppNHp and
      adenosine were also occluded.4. WEC cell membranes were able to metabolize a
      trace concentration (6 nM) of [3H]-AMP to [3H]-adenosine under the conditions of
      the binding assay. The pIC50 values of adenosine (5.99), GMP (7.55)and the
      substrate AMP (7.19) for inhibiting this [3H]-AMPase activity were almost
      identical to their high affinity pIC50 estimates obtained in the binding assay.
      Although alpha, beta-meADP, alpha, beta-meATP, beta,upsilon-meATP,ATP, ADP and
      GppNHp identified heterogeneity in the [3H]-AMPase activity of the WEC cells,
      theirpIC50 values for inhibiting the major portion of the [3H]-AMPase activity
      were similar to their respective high affinity pIC50 values in the binding assay.
      It thus seems likely that WEC cells express a form of 5'-nucleotidase that
      possesses high affinity for both alpha,beta-meADP and alpha,beta-meATP and that
      this enzyme can be labelled by [3H]-alpha,beta-meATP.5. In the presence of 10
      microM GMP, the affinity estimates for alpha,beta-meADP, AMP, GMP, GTP,
      GppNHp,ADP and adenosine at the high affinity [3H]-alpha,beta4-meATP binding
      sites that remained available, were lowa nd similar to their affinity estimates
      at the high affinity [3H]-alpha,beta-meATP binding sites of rat vas deferens.
      Since the high affinity [3H]-alpha,beta-meATP binding sites in rat vas deferens
      are thought to be P2x purinoceptors it is possible that the high affinity [3H]
      alpha,beta-meATP binding sites in the WEC which possess low affinity for
      alpha,beta-meADP are also P2x purinoceptors.

PMID- 8548176
TI  - The enantiomers of zacopride: an intra-species comparison of their potencies in
      functional and anxiolytic models.
AB  - 1. The 5-HT3 receptor antagonist, zacopride, and its enantiomers, R(+)-zacopride
      and S(-)-zacopride, were examined in three pharmacological models: (i) 5-HT
      induced depolarization of the mouse isolated vagus nerve preparation, (ii) the 5
      HT-evoked von Bezold-Jarisch reflex in the mouse, and (iii) the mouse light:dark
      box model of anxiety. Other standard 5-HT3 receptor antagonists were also
      included for comparison in these studies. 2. Racemic zacopride, and both of the
      enantiomers, displayed potent 5-HT3 receptor antagonist activity in the isolated
      vagus nerve and in the von Bezold-Jarisch model. No 5-HT3 receptor agonist or
      partial agonist effects of these compounds were detected. 3. In the isolated
      vagus nerve, R(+)-zacopride and ondansetron were surmountable 5-HT3 receptor
      antagonists (pA2 values of 9.3 and 8.3, respectively), whereas racemic zacopride,
      S(-)-zacopride and tropisetron were insurmountable antagonists, markedly
      suppressing the maximum response to 5-HT. 4. In vivo, racemic zacopride, R(+)
      zacopride, S(-)-zacopride and WAY100289 were potent antagonists of the 5-HT
      evoked von Bezold-Jarisch reflex, with minimum effective doses (lowest dose
      required to reduce the reflex by > or = 85%; MED85) of 1.0, 3.0, 0.3 and 3.0
      micrograms kg-1, s.c., respectively. 5. Racemic zacopride, R(+)-zacopride and S(
      )-zacopride were active in the mouse light:dark box model of anxiety, with
      similar potencies (minimum effective dose 1 microgram kg-1, s.c.) and similar
      active dose-ranges (1-1000 micrograms kg-1, s.c.). 6. The doses of racemic
      zacopride, R( + )-zacopride and S(-)-zacopride required to block 5-HT3receptors
      in vivo correlated reasonably well with their potencies in an anxiety model
      within the same species. In these studies, there was no evidence of a marked
      difference between the anxiolytic potencies ofR( + )-zacopride and S(-)
      zacopride.

PMID- 8548177
TI  - Noradrenaline contractions of human prostate mediated by alpha 1A-(alpha 1c-)
      adrenoceptor subtype.
AB  - 1. The subtype of alpha 1-adrenoceptor mediating contractions of human prostate
      to noradrenaline was characterized by use of a range of competitive and non
      competitive antagonists. 2. Contractions of the prostate to either noradrenaline
      (pD2 5.5), phenylephrine (pD2 5.1) or methoxamine (pD2 4.4) were unaltered by the
      presence of neuronal and extraneuronal uptake blockers. Noradrenaline was about 3
      and 10 times more potent than phenylephrine and methoxamine respectively.
      Phenylephrine and methoxamine were partial agonists. 3. Pretreatment with the
      alkylating agent, chlorethylclonidine (10(-4M) shifted the noradrenaline
      concentration-contraction curve about 3 fold to the right and depressed the
      maximum response by 31%. This shift is 100 fold less than that previously shown
      to be produced by chlorethylclonidine under the same conditions on alpha 1B
      adrenoceptor-mediated contractions. 4. Cumulative concentration-contraction
      curves for noradrenaline were competitively antagonized by WB 4101 (pA2 9.0), 5
      methyl-urapidil (pA2 8.6), phentolamine (pA2 7.6), benoxathian (pA2 8.5),
      spiperone (pA2 7.3), indoramin (pA2 8.2) and BMY 7378 (pA2 6.6). These values
      correlated best with published pKi values for their displacement of [3H]-prazosin
      binding on membranes expressing cloned alpha 1c-adrenoceptors and poorly with
      values from cloned alpha 1b- and alpha 1d-adrenoceptors. 5. The good correlation
      between the functional data on the prostate and the binding data on the expressed
      alpha 1c-subtype clone for the affinities of the competitive antagonists suggests
      that they are the same subtype. As the expressed alpha 1c-adrenoceptor clone
      corresponds to the alpha 1A-adrenoceptor expressed in tissues, contraction of the
      human prostate to noradrenaline is therefore mediated by an alpha 1A
      adrenoceptor.

PMID- 8548178
TI  - Effects of the two enantiomers, S-16257-2 and S-16260-2, of a new bradycardic
      agent on guinea-pig isolated cardiac preparations.
AB  - 1. The electromechanical effects of two enantiomers, S-16257-2 (S57) and S-16260
      2 (R60), were studied and compared in guinea-pig isolated atria and ventricular
      papillary muscles. The possible stereoselectivity of the interaction on the
      cardiac Na+ channel was analysed by comparing the effects of the two enantiomers
      on the onset and recovery kinetics of the frequency-dependent Vmax block. 2. In
      spontaneously beating right atria, S57 and R60 (10(-8)M-10(-4M) exerted a
      negative chronotropic effect (pIC50 = 5.07 +/- 0.19 and 4.76 +/- 0.18,
      respectively) and prolonged the sinus node recovery time, this effect being more
      marked with S57. In electrically driven left atria, S57 decreased (P < 0.05)
      contractile force only at 10(-4M) and R60 at concentrations > or = 5 x 10(-5M),
      whereas in papillary muscles the negative inotropic effect appeared at
      concentrations > 10(-5M). 3. In papillary muscles driven at 1 Hz, S57 and R60 at
      concentrations higher than 5 x 10(-6M) produced a concentration-dependent
      decrease in the maximum upstroke velocity (Vmax) and amplitude of the cardiac
      action potential without altering the resting membrane potential or the action
      potential duration. S57 and R60 had no effect on the characteristics of the slow
      action potentials elicited by isoprenaline in ventricular muscle fibres
      depolarized in high K+ (27 mM) solution. 4. At 5 x 10(-5M), S57 and R60 produced
      a small tonic Vmax block. However, in muscles driven at rates between 0.5 and 3
      Hz both enantiomers produced an exponential decline in Vmax (frequency-dependent
      Vmax block) which augmented at higher rates of stimulation. The onset and offset
      rates of the frequency-dependent Vmax block were similar for both drugs. Both S57
      and R60 prolonged the recovery time constant from the frequency-dependent block
      from 20.1 +/- 2.9 ms to 2-3 s.5. At 5 x 10-5 M, S57 and R60 shifted the membrane
      responsiveness curve in a hyperpolarizing direction.6. It can be concluded that
      S57 and R60, the two enantiomers of the new bradycardic agent, produced a similar
      frequency-dependent Vmax block which indicated that the interaction with the Na+
      channel was not stereospecific. The analysis of the onset and offset kinetics of
      the frequency-dependent Vmax block suggested that both enantiomers can be
      considered as Na+ channel blockers with intermediate kinetics,e.g., class IA
      antiarrhythmic drugs.

PMID- 8548179
TI  - Mechanisms of angiotensin II chronotropic effect in anaesthetized dogs.
AB  - 1. The chronotropic effect of angiotensin II (5 micrograms in 1 ml of Tyrode
      solution), injected directly into the sinus node artery of 24 anaesthestized and
      vagotomized dogs pretreated with a beta-adrenoceptor antagonist, was evaluated
      before and after the administration of: (a) an angiotensin II AT1 receptor
      antagonist (losartan, 50 micrograms kg-1 min-1 infused i.v. for 120 min), (b) an
      alpha-adrenoceptor antagonist (prazosin, 1 mg kg-1 i.v. bolus injected), (c) a
      Ca2+ channel blocker (nifedipine 50, 100 and 200 micrograms kg-1 i.v. bolus
      injected) and (d) a protein kinase inhibitor (staurosporine, 800 nM infused via
      the sinus node artery at 0.6 ml min-1 for 15 min). 2. Losartan and staurosporine
      by themselves had no effect on basal systemic arterial pressure and heart rate,
      whereas prazosin and nifedipine caused significant diminutions of both
      parameters. 3. Angiotensin II induced significant increases in heart rate, the
      mean augmentations being 29 +/- 2 beats min-1. Losartan, nifedipine and
      staurosporine significantly decreased the chronotropic effect of angiotensin II,
      the mean respective diminutions being 65 +/- 8, 40 +/- 9 and 64 +/- 10%, whereas
      prazosin had no effect. 4. This work has demonstrated that angiotensin II exerts
      in vivo a significant positive chronotropic effect that is mediated via AT1
      receptors located in the region of the sinoatrial node. This effect is
      independent of the adrenergic system. It is decreased by the inhibition of the
      production of protein kinases, most probably of protein kinase C, and by the
      blockade of the voltage-sensitive L-type Ca2+ channels. Other studies are
      obviously needed to ascertain the role of angiotensin II in the control of heart
      rate and/or the genesis of arrhythmias.

PMID- 8548181
TI  - Regenerative caffeine-induced responses in native rabbit aortic endothelial
      cells.
AB  - 1. Single native aortic endothelial cells obtained by enzymatic dispersion of the
      rabbit aortic endothelium were held under voltage clamp using patch pipette and
      whole-cell membrane currents were measured. In parallel experiments performed on
      cells from the same batches, the free internal calcium concentration, [Ca2+]i, in
      the cell was estimated by use of the Ca(2+)-sensitive fluorescent dye, fura-2. 2.
      Caffeine (20 mM) applied to the cell evoked an outward current and an initial
      peak in [Ca2+]i followed by a lower sustained rise (plateau). Ca(2+)-free, EGTA
      containing solution applied outside the cells did not reduce these responses. 3.
      Following caffeine stimulation there was a biphasic rising phase of outward
      current both in the presence and absence of extracellular Ca2+. 4. Application of
      graded doses of caffeine revealed all-or-none type responses of both the outward
      current and the rise in [Ca2+]i. 5. Preincubation with lower doses of caffeine
      reduced the magnitude of both the outward current and the [Ca2+]i transient
      evoked by 20 mM caffeine. 6. Tetraethylammonium (3 mM) applied to the bathing
      solution blocked unitary and spontaneous transient outward currents (STOCs)
      stimulated by Ca(2+)-free solution, but only reduced the outward current evoked
      by caffeine (20 mM). 7. In conclusion, our results reveal the all-or-none nature
      of Ca2+ release from the endoplasmic reticulum (ER) in native aortic endothelial
      cells. Lower concentrations of caffeine (0.4-0.5 mM) may deplete intracellular
      Ca2+ stores. Extracellular Ca2+ is not necessary for maintaining the activity of
      spontaneous and caffeine-induced outward currents in native aortic endothelial
      cells. Spontaneous outward currents are believed to represent the sporadic
      release of calcium from store sites independent of both extracellular Ca2+ and
      the caffeine-sensitive Ca2+ stores which stimulate the outward current.

PMID- 8548180
TI  - Adenosine A1 receptor-mediated changes in basal and histamine-stimulated levels
      of intracellular calcium in primary rat astrocytes.
AB  - 1. The effects of adenosine A1 receptor stimulation on basal and histamine
      stimulated levels of intracellular free calcium ion concentration ([Ca2+]i) have
      been investigated in primary astrocyte cultures derived from neonatal rat
      forebrains. 2. Histamine (0.1 microM-1 mM) caused rapid, concentration-dependent
      increases in [Ca2+]i over basal levels in single type-2 astrocytes in the
      presence of extracellular calcium. A maximum mean increase of 1,468 +/- 94 nM
      over basal levels was recorded in 90% of type-2 cells treated with 1 mM histamine
      (n = 49). The percentage of type-2 cells exhibiting calcium increases in response
      to histamine appeared to vary in a concentration-dependent manner. However, the
      application of 1 mM histamine to type-1 astrocytes had less effect, eliciting a
      mean increase in [Ca2+]i of 805 +/- 197 nM over basal levels in only 30% of the
      cells observed (n = 24). 3. In the presence of extracellular calcium, the A1
      receptor-selective agonist, N6-cyclopentyladenosine (CPA, 10 microM), caused a
      maximum mean increase in [Ca2+]i of 1,110 +/- 181 nM over basal levels in 30% of
      type-2 astrocytes observed (n = 53). The size of this response was concentration
      dependent; however, the percentage of type-2 cells exhibiting calcium increases
      in response to CPA did not appear to vary in a concentration-dependent manner. A
      mean calcium increase of 605 +/- 89 nM over basal levels was also recorded in 23%
      of type-1 astrocytes treated with 10 microM CPA (n = 30). 4. In the absence of
      extracellular calcium, in medium containing 0.1 mM EGTA, a mean increase in
      [Ca2+]i of 504 +/- 67 nM over basal levels was recorded in 41% of type-2
      astrocytes observed (n = 41) after stimulation with 1 microM CPA. However, in the
      presence of extracellular calcium, pretreatment with the A1 receptor-selective
      antagonist, 8-cyclopentyl-1,3-dipropylxanthine, for 5-10 min before stimulation
      with 1 microM CPA, completely antagonized the response in 100% of the cells
      observed. 5. In type-2 astrocytes, prestimulation with 10 nM CPA significantly
      increased the size of the calcium response produced by 0.1 microM histamine and
      the percentage of responding cells. Treatment with 0.1 microM histamine alone
      caused a mean calcium increase of 268 +/- 34 nM in 41% of the cells observed (n =
      34). After treatment with 10 nM CPA, mean calcium increase of 543 +/- 97 nM was
      recorded in 100% of the cells observed (n = 33). 6. These data indicate that
      adenosine Al receptors couple to intracellular calcium mobilization and
      extracellular calcium influx in type-1 and type-2 astrocytes in primary culture.
      In addition, the simultaneous activation of adenosine Al receptors on type-2
      astrocytes results in an augmentation of the calcium response to histamine H1
      receptor stimulation.

PMID- 8548182
TI  - Gi proteins and the response to 5-hydroxytryptamine in porcine cultured
      endothelial cells with impaired release of EDRF.
AB  - 1. The receptor-mediated release of endothelium-derived relaxing factor(s) (EDRF)
      requires the presence of different functional G proteins in endothelial cells.
      Release of EDRF in response to 5-hydroxytryptamine (5-HT), which involves
      activation of pertussis toxin-sensitive Gi proteins, is impaired in both
      regenerated endothelium of the coronary artery following balloon catheterization
      and in porcine cultured endothelial cells. This study used porcine cultured
      endothelial cells as a model of regenerated endothelium to determine if the
      abnormal release of EDRF in response to 5-HT may be associated with the loss of
      functional pertussis toxin-sensitive Gi proteins. 2. Binding studies on porcine
      cultured endothelial cells demonstrated specific binding sites for [3H]-5-HT.
      Scatchard analyses revealed a single binding site for [3H]-5-HT with Kd of 7.2 +/
      3.5 nM and maximal binding (Bmax) of 121.4 +/- 51.3 fmol mg-1 protein. Binding
      of [3H]-5-HT was displaced by methiothepin (5-HT1 and 5-HT2 antagonist; Ki = 6.2
      +/- 1.2 nM), but not by ketanserin (preferential 5-HT2 antagonist). 3. Gi alpha 1
      protein was expressed in cultured but not in native endothelial cells. Gi alpha 2
      and Gi alpha 3 proteins were expressed to significant levels in porcine native
      and cultured endothelial cells, as detected by Northern and Western blot
      analysis. 4. In membranes from cultured endothelial cells, two bands of 40 and 41
      kDa, which corresponded to the Gi alpha 2 and the combination of Gi alpha 3-Gi
      alpha 1 proteins, respectively, were ADP-ribosylated by pertussis toxin. The
      labelling intensity was Gi alpha 2>Gi alpha 3-Gi alpha l and the amount of ADP
      ribosylation was not different between porcine native and cultured endothelial
      cells. Stimulation of the cultured cells with 5-HT (3 x 10-6 M; 4 min) decreased
      significantly further ADP-ribosylation of Gi alpha 2 by pertussis toxin, but not
      that of Gi alpha 3 and/or Gi alpha l.5. The present results suggest that porcine
      endothelial cell culture may lead to the abnormal expression of Gi alpha l
      protein and that the dysfunctional release of EDRF from cultured porcine
      endothelial cells in response to 5-HT is not associated with the loss of Gi alpha
      proteins or the absence of 5-HT binding sites.

PMID- 8548183
TI  - Cross talk between receptors mediating contraction and relaxation in the
      arterioles but not the dilator muscle of the rat iris.
AB  - 1. Sympathetic nerve stimulation causes contraction of the dilator muscle and the
      large arterioles of the iris via the activation of alpha 1B-adrenoceptors. We
      have investigated whether increases in adenosine 3': 5'-cyclic monophosphate
      (cyclic AMP) and the activation of receptors in these tissues can modulate these
      nerve-mediated contractions. 2. Increasing intracellular cyclic AMP with
      dibutyryl cyclic AMP (1 mM), forskolin (50 microM) or isobutylmethylxanthine (100
      microM) produced relaxation of both the dilator and the arterioles, abolished the
      nerve-mediated constriction of the arterioles, but potentiated the nerve-mediated
      contraction of the iris dilator. 3. Pretreatment of the preparations with cholera
      toxin, to activate Gs permanently, caused a dilatation of the arterioles and
      abolished the nerve-mediated constriction but had no effect on the dilator
      muscle. 4. The beta-adrenoceptor agonist, isoprenaline (1 microM), the adenosine
      A1,-A2 agonist, N-ethylcarboxamidoadenosine NECA (100 nM), in the presence of the
      A1-selective antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, 10 nM), and
      calcitonin gene-related peptide (CGRP, 10 nM) all separately caused a dilatation
      of the arterioles and abolished the nerve-mediated constriction, while only
      isoprenaline (1 microM) produced an effect on the dilator, i.e. a relaxation but
      a potentiation of the nerve-mediated contraction. These results suggest the
      presence of at least 3 types of receptor linked to Gs and an increase in cyclic
      AMP in the arterioles, i.e. beta-adrenoceptor, adenosine-A2 and CGRP, but only 1
      Gs-linked receptor, i.e. beta-adrenoceptors, on the dilator muscle cells.2+ '

PMID- 8548184
TI  - Hypotensive effect of 13-hydroxylinoleic acid in the rat: mediation via the
      release of a CGRP-like mediator from capsaicin-sensitive nerves.
AB  - 1. The effect of 13-hydroxylinoleic acid (13-HODE) on changes in blood pressure
      in the rat was measured. 2. 13-HODE (0.1 - 100 micrograms kg-1) had no direct
      effect on blood pressure in the rat and had no effect on histamine (0.1 - 1000
      micrograms kg-1)-induced changes in blood pressure. In contrast, it was found
      that 13-HODE itself induced a decrease in diastolic arterial blood pressure when
      it was injected intravenously after either a single dose of histamine (10, 100 or
      1000 micrograms kg-1) or after a dose-response curve of histamine (0.1 - 1000
      micrograms kg-1). 3. This hypotensive effect of 13-HODE was not observed after
      administration of the endothelium-dependent vasodilator, acetylcholine (0.1 - 10
      micrograms kg-1), the endothelium-independent vasodilator, sodium nitroprusside
      (0.1 - 100 micrograms kg-1) or the inflammatory mediator, leukotriene B4 (0.1 -
      300 micrograms kg-1). However, prior injection of bradykinin (0.1 - 100
      micrograms kg-1) allowed a dose-dependent hypotensive effect of 13-HODE to be
      revealed. 4. The hypotensive effect of 13-HODE after histamine and bradykinin
      could be inhibited by neonatal capsaicin treatment of the rats (50 mg kg-1, s.c.
      on day 1 and 2 after birth). 5. Ruthenium red (120 micrograms kg-1 min-1), an
      inhibitor of excitatory effects on sensory nerves, and the CGRP antagonist, CGRP8
      37 (1-3 micrograms kg-1 min-1) also inhibited the hypotensive effect of 13-HODE.
      6. It is concluded that the hypotensive effect of 13-HODE in the rat after
      histamine and bradykinin is due to the release of a CGRP-like substance from
      sensory nerves. These results highlight the possibility that endogenous 13-HODE
      could be involved in the neurogenic regulation of blood pressure.

PMID- 8548185
TI  - Evidence for ETA and ETB receptors in rat skin and an investigation of their
      function in the cutaneous microvasculature.
AB  - 1. The relative contribution of ETA and ETB receptors in the response of rat skin
      to endothelins was investigated by use of the selective ETB agonist IRL-1620 and
      the selective ETA antagonist BQ-123. 2. Binding data suggest the presence of ETA
      and ETB receptors as preincubation with [Ala3,11,18Nle7]-endothelin-1 reduced ET
      1 binding by approximately 40%. 3. Intradermal injection of endothelin-1 (ET-1, 1
      10 pmol/site) and ET-3 (3-100 pmol/site) induced a dose-dependent decrease in
      local blood flow assessed by 133Xe clearance at test sites in rat skin. 4. The
      endothelin analogue [Ala3,11,18Nle7]-ET-1 (30-1000 pmol/site) induced significant
      vasoconstriction (P < 0.05) at the highest doses used and the selective ETB
      receptor agonist, IRL-1620 [Suc[Glu9,Ala11,15] endothelin (8-21)], (0.01-100
      pmol/site) acted in a potent manner to induce a significant (P < 0.01) dose
      dependent decrease in 133Xe clearance. 5. Co-injection with the selective ETA
      receptor antagonist, BQ-123 (1 nmol/site), completely abolished the
      vasoconstriction to ET-1 and partially to ET-3, but had no effect on IRL-1620
      induced vasoconstriction. In addition, IRL-1620 responses were not altered at
      sites treated with submaximal doses of a nitric oxide synthase inhibitor or a
      prostaglandin synthase inhibitor. 6. ET-1 and IRL-1620 (100 fmol-1 pmol/site) did
      not induce oedema formation as measured by [125I]-albumin accumulation in the
      presence or absence of the vasodilator, calcitonin gene-related peptide (CGRP).
      ET-1 (1-3 pmol/site) inhibited substance P-induced oedema formation and this
      effect,suggested to be secondary to a vasoconstrictor effect, was significantly
      reversed by BQ-123 (1 nmol/site).7. The findings in this study indicate that
      there are ETA and ETB receptors in rat skin and agents which activate either
      receptor act to mediate a decrease in cutaneous blood flow, but have no effect on
      increased microvascular permeability.

PMID- 8548186
TI  - BaCl2- and 4-aminopyridine-evoked phasic contractions in the rat vas deferens.
AB  - 1. The actions of BaCl2 and 4-aminopyridine, blockers of K+ channels, on the
      mechanical activity of the epididymal half of the rat vas deferens were
      investigated. 2. Both BaCl2 and 4-aminopyridine dose-dependently evoked phasic
      contractions. High extracellular potassium (35-40 mM) caused a tonic contraction
      but abolished the BaCl2- and 4-aminopyridine-induced phasic activity and reduced
      the BaCl2-induced sustained component of contraction, but increased the 4
      aminopyridine-induced tonic contraction. 3. Omission of calcium from the
      extracellular medium totally abolished the 4-aminopyridine-induced response but
      only reduced the mean amplitude of phasic contractions induced by BaCl. 4.
      Procaine (10 mM), an inhibitor of internal calcium release, completely abolished
      the phasic activity and reduced the sustained contraction induced by BaCl2. The
      remaining tone was abolished by nifedipine (1 microM). 5. Tetraethylammonium (1
      mM) suppressed the amplitude of the BaCl2-induced phasic contractions, and
      induced a biphasic increase in tonic tension. 6. The BaCl2-induced responses were
      resistant to prazosin (1 microM), yohimbine (3 microM), propranolol (3 microM) or
      atropine (3 microM); in contrast, the 4-aminopyridine-induced activity was
      effectively inhibited by prazosin (1 microM) attenuated by yohimbine (1 microM)
      and atropine (1 microM) but not by propranolol (3 microM). The 4-aminopyridine
      induced response was abolished by pretreatment of the vas deferens with 6
      hydroxydopamine (0.5 mM). 7. The results indicate that the BaCl2-evoked activity
      in the vas deferens was mainly due to blockade of Ba(2+)-sensitive K+ channels on
      the smooth muscle plasma membrane. Subsequent calcium entry through the
      depolarized plasma membrane was needed to trigger generation of phasic
      contractions. 4-Aminopyridine-induced action, however, was largely mediated by
      neurotransmitters released from the depolarized nerve terminals as a result of
      blockade of K+ channels.

PMID- 8548187
TI  - Role of nitric oxide in learning and memory and in monoamine metabolism in the
      rat brain.
AB  - 1. We investigated the effects of NG-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of nitric oxide (NO) synthase, on the performance of rats in a radial
      arm maze and in habituation tasks, and on monoamine metabolism in the brain. 2.
      Daily administration of L-NAME (10-60 mg kg-1) resulted in a dose-dependent
      impairment of performance during the acquisition of the radial arm maze task,
      while it failed to affect performance in those rats that had previously acquired
      the task. 3. The rate of decrease in locomotor activity in the habituation task
      in the L-NAME-treated rats was significantly less than that in control rats. 4.
      NG-nitro-D-arginine methyl ester (D-NAME, a less active inhibitor of NO synthase)
      showed no effects in the above behavioural tasks. 5. NO synthase activity was
      significantly decreased in both the L-NAME and D-NAME-treated rats, with the
      magnitude of inhibition being greater in the L-NAME-treated animals. 6. The
      content of 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and the 5
      HIAA/5-hydroxytryptamine ratio in the hippocampus and cortex were significantly
      decreased in the L-NAME (60 mg kg-1)-treated rats compared with these values in
      the controls. 7. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) content was
      significantly increased in the L-NAME (60 mg kg-1)-treated rats compared with the
      values in the controls, while the DOPAC/dopamine ratio was not changed. 8. These
      results suggest that: (i) NO may play an important role in performance during the
      acquisition,but not retention, of the radial arm maze task, and (ii) that
      endogenous NO may be involved in the regulation of monoamine metabolism.

PMID- 8548189
TI  - Herpes simplex virus resistance to acyclovir: clinical relevance.
AB  - Herpes simplex virus (HSV) infections are very common in the general population
      and can be treated with the nucleoside analogue acyclovir. Acyclovir is initially
      phosphorylated intracellularly in HSV-infected cells by a viral-specific
      thymidine kinase to acyclovir-monophosphate. The monophosphate is subsequently di
      and triphosphorylated by host cellular kinases to the active form of the drug,
      which inhibits HSV DNA polymerase and incorporates into the elongating viral DNA
      and causes chain termination. Acyclovir resistance has been increasingly
      described and is caused by mutations in either the thymidine kinase or the DNA
      polymerase genes. These mutations result in decreased or absent HSV thymidine
      kinase production, altered affinity of the thymidine kinase for acyclovir
      triphosphate, or altered affinity of the HSV DNA polymerase for acyclovir
      triphosphate. Thymidine kinase deficiency accounts for approximately 95% of
      acyclovir-resistant isolates. Clinical disease due to acyclovir-resistant HSV
      occurs primarily in immunocompromised patients and is usually characterized by a
      chronic, progressive ulcerative mucocutaneous disease with prolonged shedding of
      virus. Several large surveys have been done in an effort to determine the
      incidence of in vitro and clinical acyclovir resistance. Among immunocompetent
      hosts, even those who have received > or = 6 years of continuous acyclovir, the
      prevalence of acyclovir-resistant isolates has remained stable at approximately
      3%. Only three cases of clinical resistance of HSV to acyclovir have been
      reported. However, the incidence in immunocompromised patients, particularly
      those with AIDS and those who have had bone marrow transplants, is increasing.
      Transmission of acyclovir-resistant isolates from person to person has not been
      documented, but due to the increased use of acyclovir and newer drugs, such as
      famciclovir, there is great concern that this transmission might occur in the
      future. Continued surveillance in both immunocompetent and immunocompromised
      hosts for the development of clinical acyclovir-resistant HSV disease is
      necessary.

PMID- 8548188
TI  - Endothelial function in spontaneously hypertensive rats: influence of quinapril
      treatment.
AB  - 1. Angiotensin converting enzyme (ACE) inhibition has been shown to restore the
      impaired endothelial function in hypertension, but the mediators underlying the
      promoted endothelium-dependent dilatation have not been fully characterized.
      Therefore, we investigated the effects of 10-week-long quinapril therapy (10 mg
      kg-1 day-1) on responses of mesenteric arterial rings in vitro from spontaneously
      hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Endothelium
      dependent relaxations of noradrenaline (NA)-precontracted rings to acetylcholine
      (ACh) and adenosine 5'-diphosphate (ADP) were similar in WKY rats and quinapril
      treated SHR and more pronounced than in untreated SHR. The nitric oxide (NO)
      synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the
      relaxations in both WKY groups and quinapril-treated SHR, and completely
      inhibited them in untreated SHR. When endothelium-dependent hyperpolarization was
      prevented by precontraction of the preparations with potassium chloride (KCl), no
      differences were found in relaxations to ACh and ADP between the study groups. In
      addition, in NA-precontracted rings the L-NAME- and indomethacin-resistant
      relaxations to ACh were partially prevented by apamin, an inhibitor of calcium
      activated potassium channels. 3. Interestingly, in quinapril-treated SHR but not
      in the other groups, exogenous bradykinin potentiated the relaxations to ACh in
      both NA- and KCl-precontracted arterial rings. 4. Contractile sensitivity of
      endothelium-intact rings to NA was reduced in SHR by quinapril, and was more
      effectively increased by L-NAME in quinapril-treated than untreated SHR. 5. In
      conclusion, since the relaxations to ACh and ADP in quinapril-treated SHR were
      augmented in the absence and presence of NO synthesis inhibition but not under
      conditions which prevented hyperpolarization, enhanced endothelium-dependent
      relaxation after long-term ACE inhibition can be attributed to increased
      endothelium-dependent hyperpolarization. However, the potentiation of the
      response to ACh by exogenous bradykinin in quinapril-treated SHR, as well as the
      increased attenuating effect of the endothelium on NA-induced contractions in
      these animals appear to result from enhanced endothelium-derived NO release.

PMID- 8548190
TI  - Morbilliviruses and morbillivirus diseases of marine mammals.
AB  - In recent years, serious disease outbreaks among seals and dolphins were
      attributed to infection with established or newly recognized morbilliviruses. The
      first identification of a morbillivirus as causative agent of mass mortality
      among marine mammals was in 1988, when the previously unrecognized phocine
      distemper virus (PDV) caused the death of 20,000 harbor seals (Phoca vitulina) in
      northwestern Europe. A similar epizootic among Baikal seals (Phoca sibirica) in
      Siberia in 1987 was later attributed to infection with canine distemper virus
      (CDV). A morbillivirus isolated from stranded harbor porpoises (Phocoena
      phocoena) between 1988 and 1990 proved to be yet another new member of the genus
      Morbillivirus, distinct from PDV and CDV and more closely related to rinderpest
      virus and peste-des-petits-ruminants virus: porpoise morbillivirus. A similar
      virus, dolphin morbillivirus, was the primary cause of mass mortality among
      striped dolphins (Stenella coeruleoalba) in the Mediterranean from 1990 to 1992.
      In this review, current knowledge of the genetic and antigenic relationships of
      these viruses is presented, and the origin and epizootiological aspects of the
      newly discovered morbilliviruses are discussed. In addition, the possible
      contributory role of environmental contaminant-related immunosuppression in the
      severity and extent of the different disease outbreaks is discussed.

PMID- 8548191
TI  - Controversies in the treatment of cytomegalovirus retinitis: foscarnet versus
      ganciclovir.
AB  - Cytomegalovirus (CMV) retinitis is the most common intraocular infection in
      patients with AIDS. Untreated, CMV retinitis is a binding disease. Ganciclovir, a
      nucleoside analog, and foscarnet, a pyrophosphate analog, are both effective in
      controlling CMV retinitis. A randomized, controlled, comparative trial of
      foscarnet and ganciclovir demonstrated that they were equivalent in terms of
      controlling CMV retinits, but that foscarnet was associated with a longer
      survival, possibly due to an antiretroviral effect of foscarnet. However,
      foscarnet was less well tolerated than ganciclovir, primarily due to the nature
      of its side effects. Because foscarnet and ganciclovir have different side
      effects, initial treatment of CMV retinitis should be individualized. Newer
      technological developments, including oral ganciclovir and the ganciclovir
      intraocular device, may influence the choice of initial treatment, particularly
      because of their effect on the quality of life when compared to chronic
      intravenous therapy. The occurrence of relapse and the development of resistance
      remain long-term concerns, which may alter the use of anti-CMV drugs over time.

PMID- 8548192
TI  - Blood-feeding arthropods: live syringes or invertebrate pharmacologists?
AB  - The habit of blood feeding evolved independently several times among the > 14,000
      species and 400 genera of hematophagous arthropods. The specific need to remove
      blood from the host's skin led to sophisticated mechanical adaptations in
      invertebrate mouthparts. Moreover, the need to counteract the vertebrate host's
      hemostasis led to the evolution of salivary antihemostatic compounds injected
      into the host by these same mouthparts. The convergent evolution scenario for
      hematophagy has resulted in a large diversity of salivary anticlotting,
      antiplatelet, and vasodilatory substances. Thus, in addition to excelling as
      phlebotomists, hematophagous arthropods excel as pharmacologists.

PMID- 8548193
TI  - Immunoglobulin gene usage in the human anti-pathogen response.
AB  - The human antibody response to foreign pathogens is generated to a relatively
      small number of target surface proteins and carbohydrates that nonetheless have
      an extensive array of epitopes. The study of human monoclonal antibodies to
      different pathogens shows that there are a diversity of mechanisms used to
      generate a sufficient repertoire of antibodies to combat the invading pathogens.
      Although many different immunoglobulin gene elements are used to construct the
      anti-pathogen response, some elements are used more often than would be expected
      if all elements were used randomly. For example, the immune response to
      Haemophilus influenzae polysaccharide appears to be quite narrow, being
      restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light
      chain family II member, 4A. In contrast, for the immune response to
      cytomegalovirus proteins, a wider group of gene elements is needed. It is also
      surprising that despite an investigator bias for IgG- rather than IgM-secreting
      immortal B cells (because of their high affinity and neutralizing abilities), 26%
      of light chains and 13% of heavy chains showed a very low level of somatic
      mutation, equivalent to an IgM molecule that has not undergone affinity
      maturation. Although some highly mutated IgG molecules are present in the anti
      pathogen response, most of the monoclonal antibodies specific for viruses or
      bacteria have a level of somatic hypermutation similar to that of the adult IgM
      repertoire. A number of studies have shown that there are similarities in the
      antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8548194
TI  - Specialized surface adaptations of Giardia lamblia.
AB  - Although Giardia lamblia trophozoites were first described by Von Leeuwenhoek in
      his own diarrheic stool, relatively little is known of the basic biology of this
      common parasite or the pathophysiology of giardiasis. In particular, there is
      little specific information about trophozoite properties that cause diarrhea, as
      neither toxins nor conventional virulence factors have been identified.
      Therefore, parasite adaptations that promote cyst survival in the external
      environment and infection and trophozoite persistence in the small intestine, may
      be viewed as key virulence properties. This review focuses on unusual surface
      structures of the trophozoite and cyst forms that enable Giardia to be such a
      successful parasite.

PMID- 8548195
TI  - Will pathologists play as important a role in the future as they have in the past
      against the challenge of infectious diseases.
AB  - Since the recognition less than 120 years ago that organisms visible only
      microscopically are capable of causing human diseases, pathologists have played a
      major role in identifying and characterizing the etiologic infectious agents and
      in elucidating the pathogenic mechanisms. In face of the opportunities and
      challenges presented by molecular technology, AIDS and other emerging infections,
      and the evolution of health care systems, it is worthwhile to question whether
      the field of pathology will continue in the future to make major contributions in
      the field of infectious diseases. The AIDS epidemic has awakened pathologists to
      the need to reemphasize infectious diseases in diagnostic anatomic and clinical
      pathology, basic and applied research, and medical and scientific education. The
      knowledge and skills of pathologists are uniquely critical to the achievement of
      efficient advances in infectious diseases, and will remain so provided that
      pathologists embrace molecular science and apply it as a principal component in
      their methodologic and conceptual armamentarium.

PMID- 8548196
TI  - Immunological responses to phospholipase-A of Salmonella typhi.
AB  - A 39 kD phospholipase-A was purified from Salmonella typhi. The enzyme was
      efficiently concentrated by precipitation with ammonium sulphate and purified by
      sequential use of column chromatography on DEAE-Sephacel and Sephadex G-100.
      Humoral and cellular immune responses were determined against both crude and
      purified phospholipase-A. Crude fraction was found to be more immunogenic than
      purified fraction.

PMID- 8548197
TI  - An adenovirus-herpes simplex virus glycoprotein B recombinant (Ad-HSV.gB)
      protects mice against a vaccinia HSV.gB and HSV challenge.
AB  - We investigated the mechanism by which mice immunized with an adenovirus-herpes
      simplex glycoprotein B recombinant (Ad-HSV.gB) are protected from challenge with
      a vaccinia (Vac)-HSV.gB and the cognate virus, HSV. C57/BL mice immunized
      intraperitoneally with Ad-HSV.gB were protected against an intracerebrally
      inoculated lethal dose of a Vac-HSV.gB or HSV-1. CD8+ cytotoxic T lymphocytes but
      not interferon-gamma-dependent mechanisms play a major role in the clearance of
      both viruses from the central nervous system. These results demonstrate that the
      administration of two recombinant viruses carrying the same foreign insert for
      either immunization or challenge in a mouse protection model provides useful
      information about the protective nature of the inserted gene product.

PMID- 8548198
TI  - Comparison of Petrifilm method to conventional methods for enumerating aerobic
      bacteria, coliforms, Escherichia coli and yeasts and molds in foods.
AB  - The Petrifilm plates method was compared to conventional methods (PCA, VRBA,
      Levine EMB agar and OGYE agar) for enumeration of mesophilic aerobic bacteria,
      coliforms, Escherichia coli, and yeasts+molds in six homogeneous lots of
      different food groups (pasteurized milk, yoghurt ice cream, eggs, minced meat,
      fresh strawberries and frozen green beans). For all the microbiological criteria
      except for yeasts and molds and mesophilic aerobic bacteria in frozen green
      beans, the mean values of counts with Petrifilm plates were higher than those
      obtained with traditional methods. The correlation coefficient of Petrifilm
      aerobic bacteria, coliforms, and yeasts + molds v. PCA, VRBA and OGYE agar for
      each microbiological criterion for a composite of six food products were 0.897,
      0.861 and 0.981, respectively.

PMID- 8548199
TI  - Interaction of immunomodulant substances in mouse experiments with special regard
      to drug sensitivity and bacterial translocation.
AB  - In acute toxicity experiments changes in drug sensitivity and in the rate of
      bacterial translocation (BT) were investigated in mice treated with
      immunomodulatory drugs: dianhydrogalactitol (DAG) in doses 20 and 30 mg/kg,
      chlorpromazine (CPZ) in doses 60 and 75 mg/kg and Mannozym (M) in dose equivalent
      to 40 mg per kg zymosan. The drugs were used separately or in combination. The
      sensitivity of mice to immunosuppressive DAG or CPZ was higher in the case of
      combined treatment than that of separately treated ones. The rate of BT was also
      higher in mice receiving combined treatment. Pretreatment with M exerting an
      immunostimulatory effect, influenced neither the sensitivity of mice to DAG or
      CPZ nor the very low normal rate of BT. The present results reinforced the
      authors' earlier observations that the effects of immunosuppressive drugs
      cumulated in and caused more serious damage of the organism. The increase in drug
      sensitivity to immunosuppressive agents may be connected with an increased rate
      of BT and effect of endotoxin.

PMID- 8548200
TI  - The number of glucocorticoid receptors in peripheral human lymphocytes is
      elevated by a zinc containing trace element preparation.
AB  - A trace element preparation (Beres Drops Plus, BDP) elevates the number of
      glucocorticoid receptors (gcR) in peripheral lymphocytes isolated both from
      healthy blood donors and rheumatoid arthritis patients. This enhancement by BDP
      was found either for constitutive expression of gcRs or in experiments when the
      lymphocytes were stimulated by interleukin (IL)-6. There was no significant
      effect of BDP on IL-1 and tumour necrosis factor alpha (TNF alpha)-induced
      changes of gcRs. The effect of BDP was greatly dependent on the presence of Zn++
      ions in the preparation, since the augmenting effect was abolished if BDP did not
      contain zinc.

PMID- 8548201
TI  - Interaction between tricyclic psychopharmacons and some antibiotics.
AB  - The tricyclic psychopharmacons, e.g. clozapine, promethazine and imipramine cure
      plasmids and inhibit plasmid transfer among bacteria due to the inhibition of
      supercoiling activity on DNA gyrase. In addition an interaction was found between
      clozapine, imipramine, promethazine and some antibiotics, e.g. penicillins and
      tetracycline in vitro. The nature of interaction is based on a charge transfer
      complex, which is formed between clozapine, imipramine, promethazine and
      penicillins. Differential spectrophotometry showed that ampicillin reduced the
      highest energy peaks of clozapine, promethazine and imipramine. Streptomycin did
      not alter the spectrum of clozapine; however, tetracycline somewhat reduced all
      the peaks of clozapine. Clozapine and promethazine exhibited a synergistic effect
      with ampicillin, tetracycline and gentamicin on Escherichia coli cells in in
      vitro. This kind of interaction was missing in the case of imipramine.

PMID- 8548202
TI  - Resistance to beta-lactam antibiotics and beta-lactamase production of
      Bacteroides, Porphyromonas and Prevotella strains.
AB  - Resistance to beta-lactam antibiotics of 183 clinical isolates belonging to
      Bacteroides, Porphyromonas and Prevotella was tested by a micro-broth dilution
      MIC method. Beta-lactamase production was screened by using nitrocefin sticks.
      Prevalence of resistance to different beta-lactam antibiotics was higher among
      the Bacteroides strains other than B. fragilis parallel with a beta-lactamase
      production (88% and 96%, respectively). Resistance was observed less frequently
      among Porphyromonas and Prevotella strains. Cefoxitin resistance was 11.5% and
      amoxicillin/clavulanic acid 3.5% among Bacteroides isolates, whereas no
      resistance was found to these antibiotics among the Porphyromonas and Prevotella
      strains. All strains tested were susceptible for imipenem. Beta-lactamase
      production of selected isolates was tested quantitatively. Beta-lactamase of B.
      fragilis 1 and B. levii differed in their isoelectric points, substrate profiles
      and inhibition by clavulanic acid, sulbactam and tazobactam.

PMID- 8548203
TI  - Effects of pentoxifyllin and PentaglobinO on TNF and IL-6 production in septic
      patients.
AB  - Pentoxifylline inhibited the TNF production of purified human white blood cells
      and whole blood cultures stimulated either by LPS or by Staphylococcus aureus.
      PTX did not influence the CD14 expression. The in vitro TNF and IL-6-producing
      capacities of septic patients were higher than in the control group.
      Administration of PTX to septic patients resulted in the normalization of TNF
      synthesis and in a moderate decrease in IL-6 production. It also subsequently led
      to an improvement in the clinical status. A further improvement in APACHE II
      score could be achieved by administration of PentaglobinO (Biotest). The
      prevention of in vitro TNF production by PentaglobinO could be demonstrated
      involving the use of whole blood rather than purified lymphocytes. The level of
      soluble ICAM-1 in the serum of septic patients was significantly higher than in
      normal individuals, but it decreased following PTX and PentaglobinO therapy. It
      is presumed that PTX and PentaglobinO can antagonize cytokine production at
      different levels, resulting in synergistic action that is beneficial in the
      treatment of sepsis.

PMID- 8548204
TI  - The entire rne gene: the remaining questions.
AB  - A 30-fold overexpression of the entire rne gene results in a 3-fold increase in
      RNase E activity. The overexpression of cloned rne fragments suggests that
      synthesis of the Rne protein is autoregulated and this regulation is related to
      the RNase E activity of the gene product. The enzyme produced by the cloned gene
      has an enhanced thermolability. The thermal stability of the temperature
      sensitive enzyme increases when the cells are cultivated in the presence of
      chloramphenicol, which suggests posttranslational alterations.

PMID- 8548205
TI  - Complement C4, factor B and C3 polymorphism in north India.
AB  - Allotype frequencies of complement C4, factor B and C3 proteins were determined
      in 192 healthy unrelated individuals from North India. The gene frequencies for
      the most common factor B and C3 alleles were close to the data already published.
      As expected, significant differences were observed in this first study of C4
      allotype frequencies among the North Indian population in comparison to European
      Caucasians. According to historians, Hungarian Gypsies migrated from India. In
      this study we demonstrate that our data for some complement allele frequencies
      are in accordance with the opinion of historians.

PMID- 8548206
TI  - Study on the glycoprotein nature of chicken IFNs by chemical cleavage and
      inhibition of glycosylation.
AB  - The considerable molecular heterogeneity of chicken IFNs suggested the possible
      glycoprotein nature of these IFNs. The carbohydrate-specific oxidation and
      cleavage by neuraminidase indicated that fibroblast IFN may contain sugar
      moieties. Among the antimetabolites preventing glycosylation, monensin diminished
      IFN production. However, since it had the same effect on unglycosylated human
      leukocyte IFN, the drug very probably blocks intracellular transport. It rather
      proved that chicken IFNs are also secretory proteins. Tunicamycin diminished the
      formation of leukocyte IFN, but the decrease in titre of this IFN is due to the
      inhibition of protein synthesis. It is suggested that chicken fibroblast IFN is a
      glycoprotein, while leukocyte IFN lacks a sugar moiety. The IFN produced on
      induction with mitogen is closely related to leukocyte IFN, and therefore it
      seems that the chicken IFN system does not involve the conventional gamma type.

PMID- 8548207
TI  - Necrotizing enterocolitis.
AB  - Advances in neonatal care have resulted in an enlarging population of vulnerable
      premature newborns at risk for necrotizing enterocolitis (NEC). This article
      presents data supporting a unifying hypothesis for the initiation of NEC based on
      bacteria as the inciting agent(s), and the preterm baby as the vulnerable host.
      Facts and controversies concerning the pathology, microbiology, clinical
      presentation, management and outcome of infants afflicted with NEC are presented.

PMID- 8548208
TI  - Catheter sepsis: the central venous line Achilles' heel.

PMID- 8548209
TI  - Antibiotic-induced colitis.
AB  - Most cases of antibiotic-associated diarrhea can be classified into two
      categories: cases in which Clostridium difficile is implicated and cases in which
      no putative agent or recognized pathophysiological mechanism is recognized. C
      difficile colonization produces a spectrum of conditions, ranging from
      asymptomatic carriage to fatal pseudomembranous colitis: it is implicated in
      virtually all cases of pseudomembranous colitis and up to 25% of cases of
      antibiotic-associated diarrhea without colitis. Clindamycin is notorious for its
      propensity to induce C difficile colitis, but in current practice, broad-spectrum
      penicillins and cephalosporins are the most frequently implicated agents,
      reflecting their widespread use. Treatment includes cessation or alteration of
      antimicrobial therapy when possible, provision of supportive care, and specific
      therapy aimed at eradicating C difficile if symptoms are severe or persistent or
      if antibiotic therapy cannot be safely discontinued. Oral metronidazole or
      vancomycin is equally efficacious in uncomplicated disease; optimal therapy for
      severe disease has not been established. Relapses occur in up to 15% of cases and
      cannot be accurately predicted or prevented.

PMID- 8548210
TI  - The significance of Helicobacter pylori colonization of the stomach.
AB  - Helicobacter pylori (Hp) was discovered in 1982 by the Australians Robin Warren
      and Barry Marshall. Initially rejected by a skeptical scientific community, it
      has since gained worldwide recognition as a clinically significant bacterium. The
      incidence of colonization with Hp increases with age, affecting approximately one
      third of the world's population. Hp is uniquely capable of surviving in the acid
      environment of the stomach, and has properties of adherence to epithelial cells
      that resist parastalsis. Strains of Hp associated with human disease produce
      specific cytotoxic proteins. After ingestion, there is a period of intense
      proliferation and ensuing gastric inflammation that may result in chronic
      gastritis. Hp infection in children may produce symptomatic antral gastritis or
      duodenal ulceration. The diagnosis of Hp infection is confirmed by gastric biopsy
      and culture, where the organism is recognized by its characteristic histological
      appearance. Treatment for Hp includes combinations of bismuth amoxicillin and
      metronidazole administered for several weeks. In adults, chronic infection with
      Hp is associated with chronic gastritis, achlorhydria, and gastric cancer. An
      organism that was unheard of 15 years ago is now recognized as a clinically
      significant pathological entity. The ultimate significance of Hp as an agent of
      disease remains to be seen.

PMID- 8548211
TI  - Pediatric soft tissue infections.
AB  - Quite often a soft tissue infection in a child may be the primary reason for
      seeking medical attention or an incidental finding on examination. To identify
      those infections that may be serious and require further intervention, all those
      dedicated to the care of children must be familiar with these illnesses and their
      complications. This article covers selected bacterial, viral, and fungal
      infections of the skin, subcutaneous fat, fascia, and muscle. Special
      considerations for the immunosuppressed child will also be discussed.

PMID- 8548212
TI  - Perforated appendicitis: past and future controversies.
AB  - Although mortality rates for pediatric appendicitis have been reduced to near
      zero with the development of safe surgical procedures and routine perioperative
      antibiotic therapy, the incidence of perforated appendicitis in children has
      remained at a comparatively high level. This article reviews the recent
      literature on perforated pediatric appendicitis, including a discussion of some
      of the controversies concerning management of the ruptured appendix. In addition,
      the future of both the evaluation and treatment of this disease, including
      laparoscopy, the possibilities for outpatient antibiotic therapy, and the
      worrisome potential for a change in referral patterns as children with this
      disease are increasingly enrolled in managed care plans, are considered.

PMID- 8548213
TI  - Mycotic infections in pediatric surgical patients.
AB  - Mycotic infections have become an increasingly common problem in immunosuppressed
      pediatric patients. The management of fungal infections requires not only the
      recognition of the potential for infection, but also of the types of organisms
      that can cause infection. The identification of the organ system(s) affected is
      important in directing therapy. The immature immune system of neonates is
      partially responsible for some specific diseases and unique management problems.
      These infants are increasingly stressed to degrees not previously seen in
      intensive care nurseries and may be on long-term antibiotic therapy for other
      illnesses. Chemotherapy for malignancy, bone marrow transplants, trauma, and
      chronic illness increase the risk of immunocompromise and systemic fungal
      infections. The frequent use of long-term intravascular catheters contributes to
      the potential for fungal infection in the pediatric population. Therapy now
      includes administration of topical and/or parenteral antifungal agents and
      supportive care to the patients. New therapies may well include more potent and
      safer antifungal agents as well as new ways to enhance the immune response in
      immunosuppressed patients.

PMID- 8548214
TI  - Opportunistic infections in immunocompromised patients.

PMID- 8548216
TI  - Music in the operating theatre.

PMID- 8548215
TI  - Human immunodeficiency virus and acquired immunodeficiency syndrome: recent
      developments and their implications for pediatric surgeons.
AB  - Advances in medical management have enhanced both the quality and the quantity of
      life currently enjoyed by HIV-infected infants and children. Advances in surgical
      treatment have complemented these advances and contributed to the improving
      prognosis of HIV disease in the pediatric population. The resultant "aging" of
      the pediatric HIV population means that pediatric surgeons can expect to
      encounter HIV-infected patients on an ever-increasing basis. This article reviews
      the new advances in diagnosis and treatment of pediatric HIV disease most
      relevant to pediatric surgical practice.

PMID- 8548217
TI  - Factitious disorders and the surgeon.

PMID- 8548219
TI  - Clinical biology of nitric oxide.
AB  - Nitric oxide is a pluripotential molecule that acts as both an autocrine and
      paracrine mediator of homoeostasis, and derangement of its metabolism can be
      linked with many pathophysiological events. This review provides a broad overview
      of the basic and clinical scientific aspects of nitric oxide.

PMID- 8548218
TI  - Management of the pancreatic stump following pancreaticoduodenectomy.
AB  - Pancreaticoduodenectomy is the procedure of choice in patients with periampullary
      and pancreatic cancers. Dramatic improvements in morbidity and mortality rates
      following pancreaticoduodenectomy have been reported in the past 5 years.
      Consequently, the indications for pancreaticoduodenectomy are becoming more
      liberal, with some authors suggesting its use as a palliative procedure in
      pancreatic cancer and as definitive treatment for benign diseases such as chronic
      pancreatitis. Complications are frequently related to the pancreatic stump and
      can have a fatal outcome. Several methods of managing the pancreatic stump have
      been described, with variable results. Modifications of standard techniques have
      evolved over time in an effort to reduce the incidence of major complications.
      The results of these methods, the role of perioperative adjuncts and the long
      term outcome of pancreaticoenteric anastomosis are reviewed.

PMID- 8548220
TI  - Trusses in the management of hernia today.
AB  - In the UK an estimated 40,000 trusses are issued annually. The rate of 700 per
      million is higher than that presently found in other countries and may be because
      of reduced access to surgery. Despite the high use of trusses little has been
      published on their effectiveness, complication rates and value. This review
      summarizes current knowledge, and concludes that further studies on the benefits
      and effectiveness of trusses need to be performed to enable patients to receive
      appropriate advice and guidance.

PMID- 8548221
TI  - Single-stage treatment for malignant left-sided colonic obstruction: a
      prospective randomized clinical trial comparing subtotal colectomy with segmental
      resection following intraoperative irrigation. The SCOTIA Study Group. Subtotal
      Colectomy versus On-table Irrigation and Anastomosis.
AB  - This multicentre study is the first prospective randomized trial to compare
      subtotal colectomy with segmental resection and primary anastomosis following
      intraoperative irrigation for the management of malignant left-sided colonic
      obstruction. Of the 91 eligible patients recruited by 12 centres, 47 were
      randomized to subtotal colectomy and 44 to on-table irrigation and segmental
      colectomy. Hospital mortality and complication rates did not differ
      significantly, but 4 months after operation increased bowel frequency (three or
      more bowel movements per day) was significantly more common in the subtotal
      colectomy group (14 of 35 versus four of 35, chi 2 = 6.06, 1 d.f., P = 0.01).
      More patients in the subtotal colectomy group reported that they had consulted
      their general practitioner with bowel problems than did those in the segmental
      resection group (15 of 37 versus three of 35, chi 2 = 8.17, 1 d.f., P = 0.004).
      Segmental resection following intraoperative irrigation is the preferred option
      except when there is caecal perforation or if synchronous neoplasms are present
      in the colon, when subtotal colectomy is more appropriate.

PMID- 8548222
TI  - Drain-site herniation of the appendix.

PMID- 8548224
TI  - Adenomatous polyps in the anal transitional zone after ileal pouch-anal
      anastomosis for familial adenomatous polyposis: treatment by transanal
      mucosectomy and ileal pouch advancement.

PMID- 8548223
TI  - Experience with ileostomy and colostomy in Crohn's disease.
AB  - This study involved 746 patients with Crohn's disease treated surgically within a
      13-year interval in whom 227 stomas (159 primary, 68 secondary) were created. The
      main indication (64 per cent) for primary stoma was severe perianal or genital
      fistulous disease. Revisional surgery for stomal complications was more common
      following colostomy than ileostomy (31 versus 5 per cent, P < 0.01). Twenty years
      after the first symptoms of Crohn's disease the cumulative risks of receiving any
      stoma or a permanent stoma were 41 and 14 per cent respectively. Four parameters
      were shown by proportional hazards analysis to be independently associated with
      the risk for any stoma as well as a permanent one; increased risk coincided with
      rectal inflammation, perianal fistula or abscess, and absence of small intestinal
      involvement. In addition, long-standing symptomatic disease before the first
      surgical intervention reduced the risk of a permanent stoma. The long-term
      chances of closure following temporary stoma were 75 per cent when used for
      anastomotic protection or avoidance, 79 per cent after postoperative
      complications, and 40 per cent for perianal or genital fistulas or for rectal
      inflammation or stenosis. Rectal disease and perianal fistula were the only
      independent predictors of a low possibility of stoma closure during follow-up.

PMID- 8548225
TI  - One-stage resection of acute sigmoid volvulus.

PMID- 8548226
TI  - Evaluation of recombinant human erythropoietin to facilitate autologous blood
      donation before surgery in anaemic patients with cancer of the gastrointestinal
      tract.
AB  - The aim of this study was to determine whether the preoperative administration of
      recombinant human erythropoietin (rHuEPO) could increase the rate of autologous
      blood donation and reduce the perioperative need for homologous blood in anaemic
      patients with cancer. Twenty-two anaemic (haematocrit less than 34 per cent),
      iron-deficient (iron less than 700 micrograms/l) patients, with gastric or
      colorectal cancer scheduled for elective surgery, were allocated randomly to two
      groups. The first (n = 11) received iron saccharate 200 mg/day intravenously for
      12 consecutive days. The second (n = 11) received rHuEPO subcutaneously (300
      units/kg as first administration, and 100 units/kg 4, 8 and 12 days later) with
      supplemental iron. On days 4, 8 and 12, if the haematocrit was greater than 34
      per cent, patients donated one unit (350 ml) of autologous blood. In the iron
      group the mean haematocrit did not change from admission (31 per cent) to day 12
      of treatment (31 per cent), and no patient could donate autologous blood. In the
      rHuEPO group, eight patients donated two units of autologous blood and three
      donated one unit. Four patients in the iron group received perioperative
      transfusion of homologous blood compared with none in the rHuEPO group.
      Administration of rHuEPO facilitated the donation of autologous blood and reduced
      perioperative homologous blood transfusion in anaemic patients with cancer.

PMID- 8548227
TI  - Non-inflammatory rectovaginal fistula.
AB  - The results of surgical repair of straightforward rectovaginal fistula in 26
      women (obstetric, 13; infection, nine; trauma, one; unknown but not radiation
      induced or related to inflammatory bowel disease, three) were ultimately
      excellent; 23 patients were cured. However, this result obscures a high early
      failure rate in five of 12 patients having a transanal advancement flap and in
      one of eight having perineoproctotomy (lay open and repair). A temporary stoma
      was used in 11 patients (five of eight with a perineoproctotomy, three of 12 with
      an advancement flap and in three having another local procedure.

PMID- 8548228
TI  - Colonoscopy for all first-degree relatives of patients with colorectal cancer.

PMID- 8548229
TI  - Bilateral gracilis neosphincter construction for treatment of faecal
      incontinence.
AB  - Neosphincter formation with gracilis muscle is used for faecal incontinence
      refractory to conservative measures and after failed sphincter repair. In this
      study both gracilis muscles were used to create a neosphincter to determine
      whether this provides superior physiological and clinical results. Ten patients
      of median age 39 (range 18-73) years were treated. The mean resting and squeeze
      pressures before operation were 16 (range 0-40) and 44 (range 0-68) cmH2O
      respectively. The operation was covered by a defunctioning loop left iliac fossa
      colostomy. Nine of the ten patients have had the stoma closed and are fully
      continent after a mean follow-up of 24 (range 6-40) months. One patient who had
      an ileoanal pouch and bilateral graciloplasty has urgency of defaecation. None of
      the patients has to wear a pad or is taking constipating agents. All nine
      patients have satisfactory evacuation on isotope defaecography and are continent
      to artificial stool. After operation the mean resting and squeeze pressures were
      78 (range 70-112) and 121 (range 90-188) cmH2O respectively. Bilateral
      graciloplasty provides satisfactory results for grade 4 faecal incontinence
      refractory to other operative and non-operative measures, and may be an
      alternative to stimulated dynamic graciloplasty.

PMID- 8548230
TI  - Laparoscopic ileostomy.

PMID- 8548231
TI  - 'Squeeze delivery' excision of subcutaneous lipoma related to anatomic site.
AB  - A small cosmetic incision followed by 'squeeze delivery' was attempted for 190
      lipomas in 116 patients. This technique was successful without resort to widening
      of the incision or using scissor dissection in 87 lipomas (46 per cent). Success
      was not related to size but to the site of the lipoma. The success rate was 100
      per cent for excision of lipomas in the forearm and leg.

PMID- 8548232
TI  - Role of transoesophageal echocardiography in determining the source of peripheral
      arterial embolism.
AB  - Thirty patients with peripheral arterial embolism underwent conventional
      transthoracic echocardiography. Transoesophageal echocardiography was also
      performed in ten of the same patients. The detection rate of cardiac
      abnormalities considered responsible for embolism was five of 20 in patients who
      received only transthoracic echocardiography and eight of ten in those who
      underwent transoesophageal echocardiography. One abnormality was detected by
      transthoracic echocardiography in the ten patients who received both tests, while
      eight cardiac or aortic abnormalities were discovered by transoesophageal
      echocardiography (P < 0.05). Transoesophageal echocardiography is significantly
      better than conventional transthoracic echocardiography at detecting cardiac
      sources of peripheral arterial embolism.

PMID- 8548233
TI  - Intracaval ultrasonography in the diagnosis of tumour involvement of the vena
      cava.
AB  - A retrospective study of 34 consecutive patients with possible tumour involvement
      of the vena cava was performed to assess the usefulness of intracaval
      ultrasonography. Twenty-five of the 34 patients were operated and resection
      carried out in 23, including seven with combined resection of the vena cava. The
      sonographic criterion for vena cava invasion was obliteration of the echogenic
      ring of the vena cava wall or intracaval tumour mass. The sensitivity,
      specificity and overall accuracy of intracaval endovascular ultrasonography in
      the diagnosis of tumour involvement of the vena cava were 100, 96 and 97 per cent
      respectively. The respective values were 91, 61 and 71 per cent for computed
      tomography and 82, 67 and 72 per cent for cavography. Ultrasonography is a useful
      technique that can precisely evaluate the vena cava for possible tumour invasion,
      especially when the presence or extent of tumour involvement is not definitely
      established by conventional imaging techniques.

PMID- 8548234
TI  - Antioxidant consumption during exercise in intermittent claudication.
AB  - Twenty male claudicant patients and nine age-matched controls were exercised on a
      treadmill. Blood and urine samples were taken before and after exercise. Total
      antioxidant concentration was measured using an enhanced chemiluminescent assay
      and microalbuminuria determined by radioimmunoassay. Claudicants had increased
      microalbuminuria after exercise. Mean (s.e.m.) antioxidant concentrations were
      similar for patients and controls at rest: 479(28) and 438(23) mumol/l
      respectively. Claudicants showed a significant decrease in antioxidant
      concentration 1 min after exercise to 428(27) mumol/l; this returned to 470(30)
      mumol/l by 10 min. A correlation was found between the decrease in antioxidant
      concentration and the increase in microalbuminuria (rs = -0.496, P < 0.05). This
      study supports the concept of ischaemia-reperfusion injury in claudicant patients
      and has implications for treatment.

PMID- 8548235
TI  - Preoperative total parenteral nutrition is not associated with mucosal atrophy or
      bacterial translocation in humans.
AB  - Concerns have recently been expressed at suggestions that postoperative sepsis
      may be more common in patients who have received preoperative total parenteral
      nutrition (TPN). The mechanism suggested for this is that TPN causes intestinal
      mucosal atrophy leading to increased bacterial translocation from the gut as a
      source of systemic sepsis. This hypothesis was examined in 203 patients who had
      an elective laparotomy, 28 of whom required at least 10 days of preoperative TPN.
      Neither mucosal atrophy nor bacterial translocation was more common in
      parenterally fed patients than in enterally fed controls. In humans theoretical
      concerns about the adverse effects of TPN on intestinal integrity are unfounded.

PMID- 8548236
TI  - Cricopharyngeus myotomy for upper airway obstruction in achalasia.

PMID- 8548237
TI  - Laparoscopic resection of a benign intragastric stromal tumour.

PMID- 8548238
TI  - Preoperative intra-aortic ultrasonography to determine resectability in advanced
      oesophageal cancer.
AB  - This study was designed to evaluate the effectiveness of intra-aortic
      ultrasonography in the preoperative diagnosis of aortic wall invasion by
      oesophageal cancer. Twenty-four patients with advanced oesophageal cancer
      underwent the procedure, and aortic invasion was found in seven. In three of
      these seven patients, the invasion was diagnosed to be limited to the aortic
      adventitia, enabling preoperative prediction of the resectability of the tumour.
      The contact angle of the tumour in relation to the descending aorta was more than
      90 degrees in six patients, and aortic invasion to all layers was visualized in
      four by intra-aortic ultrasonography. On the other hand, aortic invasion to the
      adventitia was found in three of 14 patients in whom the contact angle was less
      than 90 degrees. Intra-aortic ultrasonography provides important information to
      help determine the resectability of advanced oesophageal cancer.

PMID- 8548239
TI  - Role of the spleen in lipid metabolism.
AB  - The frequency of ischaemic heart disease observed after splenectomy for trauma
      and the low cholesterol levels found in patients with hypersplenism are
      observations that suggest a possible role for the spleen in lipid metabolism and
      in the aetiology of atherosclerosis. The present study was designed to examine
      this role in experimental animals. Serum levels of total cholesterol,
      triglyceride and high-density lipoprotein (HDL) cholesterol were determined in 32
      rats. The spleen was removed in 16 rats and the remaining 16 were sham operated.
      Half of the splenectomized and half of the remaining rats were fed on a diet rich
      in fat and the two other subgroups were fed normal chow. Blood tests were
      performed before, and 3 and 6 months after operation. A significant increase in
      serum triglyceride and decrease in serum HDL cholesterol levels was observed
      after splenectomy in rats fed normal chow compared with sham-operated rats. An
      increase in serum triglyceride and a decrease in serum HDL cholesterol levels was
      observed in both groups of rats fed normal chow plus high-fat cheese. However,
      these changes were more pronounced in splenectomized rats. These findings suggest
      that the spleen has a role in lipid metabolism in rats and may therefore
      influence atherosclerosis.

PMID- 8548240
TI  - Self-expanding metal stents for the palliation of dysphagia due to inoperable
      oesophageal carcinoma.
AB  - Adequate palliation of dysphagia due to inoperable oesophageal carcinoma is
      difficult to achieve with low morbidity. Thirty-three patients (21 men and 12
      women of mean(s.e.m.) age 69(2) years) with inoperable carcinoma of the
      oesophagus underwent insertion of self-expanding metal stents. In 22 patients the
      tumours were in the lower third of the oesophagus, in eight in the middle third
      and in three in the upper third. A stent was inserted as primary palliative
      therapy in 14 patients, after failed laser therapy in 13 and after oesophageal
      perforation following other treatments in six. Patients presented with dysphagia
      of grade 3 or 4. Three types of stent were used: Wallstent, Strecker and
      Gianturco; stents were inserted under fluoroscopic guidance after balloon
      dilatation of the stricture. All attempted insertions of metal stents were
      successful. Dysphagia reduced from grade 3 or 4 to 0 or 1. There were no
      perforations related to insertion. Patients who had stents inserted to seal
      previous perforations left hospital a median 7 days later. Dysphagia recurred in
      six patients, due to migration of the stent (three), blockage by food bolus (one)
      and tumour overgrowth (two). These problems were easily treated. Self-expanding
      metal stents seem to offer excellent palliation with minimal morbidity for
      patients with inoperable carcinoma of the oesophagus.

PMID- 8548241
TI  - Quality-of-life assessment in patients undergoing treatment for oesophageal
      carcinoma.
AB  - In a prospective study of 69 patients being treated for oesophageal carcinoma,
      quality of life was assessed with the Rotterdam Symptom Checklist, a dysphagia
      score and an activities of daily living questionnaire. Significant correlations
      were found between the results of the Rotterdam Symptom Checklist, the dysphagia
      score and most aspects of the activities of daily living questionnaire. Eighteen
      patients underwent surgery, 43 radiotherapy or intubation, and eight a
      combination of surgery and other therapy. Patients undergoing surgery were
      significantly younger and had better scores in all parameters examined before
      operation, including significantly better scores in 'knowledge and communication'
      and 'mobility and fatigue'. The dysphagia score fell significantly after
      intervention both in patients undergoing surgery alone and in those receiving
      palliative therapy. The activities of daily living questionnaire showed
      significant improvements in two parameters in the surgical group ('self-care' and
      'eating and drinking') and in none of the parameters assessed in the palliation
      group in 16 weeks. Quality-of-life assessment is useful in assessing quality of
      care and patient well-being after the diagnosis and treatment of oesophageal
      carcinoma.

PMID- 8548242
TI  - Prognostic factors after resection of ampullary carcinoma: multivariate survival
      analysis in comparison with ductal cancer of the pancreatic head.
AB  - Resection was performed in 85 patients with ampullary and in 150 with ductal
      pancreatic head carcinoma. Curative resection was achieved in 98 and 87 per cent
      respectively. Patient survival at 5 years after exclusion of hospital deaths was
      38 versus 16 per cent respectively. The patients were compared retrospectively in
      a multivariate survival analysis. For patients with pancreatic carcinoma,
      residual tumour stage, tumour size and grading were independent prognostic
      factors, but for those with ampullary carcinoma only tumour size was a prognostic
      factor. Lymph node metastasis impaired prognosis, but this effect was
      demonstrable for both groups only after univariate analysis. The Union
      Internacional Contra la Cancrum classification system was not a reliable
      parameter of prognosis after resection of ampullary carcinoma. Patients with
      ampullary cancer appear to have a better prognosis intrinsically than those with
      pancreatic head tumours, and not simply because they present at an earlier stage.
      The difference in prognosis cannot be explained sufficiently by a differential
      importance of the various survival variables.

PMID- 8548243
TI  - Laparoscopic hernia repair without the use of staples or knotting manoeuvres.

PMID- 8548244
TI  - Number of lymph node metastases is significantly associated with survival in
      patients with radically resected carcinoma of the ampulla of Vater.
AB  - Between 1983 and 1994, 66 patients with cancer of the ampulla of Vater were
      studied to identify prognostic factors and determine who might benefit from
      radical resection. Three patients (4.5 per cent) died after operation. Radical
      resection including lymphadenectomy resulted in potentially curative (R0)
      resection in 92 per cent. The rate of nodal positivity increased with tumour
      diameter. Patients with up to two positive lymph nodes had a more favourable
      prognosis than other patients (P < 0.001). Median survival time for all patients
      was 41 months; the 5-year survival rate was 35 per cent. Radical resection and
      lymphadenectomy should therefore be the treatment of choice for patients with
      tumours of the ampulla of Vater.

PMID- 8548245
TI  - Modified use of the suction curette for the management of hydatid cysts.

PMID- 8548246
TI  - Breast reconstruction after mastectomy.

PMID- 8548247
TI  - Introduction of laparoscopic cholecystectomy in a large teaching hospital:
      independent audit of the first three years.

PMID- 8548248
TI  - Randomized comparison of polyglycolic acid and polyglyconate sutures for
      abdominal fascial closure after laparotomy in patients with suspected impaired
      wound healing.

PMID- 8548249
TI  - Analysis of 8651 appendicectomies in England and Wales during 1992.

PMID- 8548250
TI  - Renal dysfunction in obstructive jaundice.

PMID- 8548251
TI  - Lothian and borders large bowel cancer project: immediate outcome after surgery.

PMID- 8548252
TI  - Prospective trial comparing Lichtenstein with laparoscopic tension free mesh
      repair of inguinal hernia.

PMID- 8548253
TI  - Laparoscopic Billroth II gastrectomy for early gastric cancer.

PMID- 8548254
TI  - Surgical treatment for morbid obesity.

PMID- 8548255
TI  - Surgical treatment of morbid obesity.

PMID- 8548256
TI  - Surgical treatment of morbid obesity.

PMID- 8548257
TI  - Effect of carbon dioxide pneumoperitoneum on bacteraemia and endotoxaemia in an
      animal model of peritonitis.

PMID- 8548258
TI  - Diagnostic laparoscopy combined with laparoscopic ultrasonography in staging of
      cancer of the pancreatic head region.

PMID- 8548259
TI  - Surgical management of rectal cancer.

PMID- 8548260
TI  - Anterior gastric wall stapling combined with posterior truncal vagotomy in the
      treatment of duodenal ulcer.

PMID- 8548261
TI  - Perioperative aspects of hip fracture. Guidelines for intervention that will
      impact prevalence and outcome.
AB  - The cost of treating osteoporosis-related diagnoses, over one half of which are
      hip fractures, is $5.2 billion per year. The incidence of hip fractures is
      rising, and it is the orthopedic surgeon who provides the definitive medical care
      to these patients. Factors associated with poor outcome in hip fractures include
      poor nutrition, impaired mental ability and mobility, age, male sex, and
      inadequate fluid resuscitation and medical stabilization prior to surgery. The
      energy requirements for fracturing the hip are low. Potential prophylactic
      interventions include fall prevention, hip protector devices, estrogen
      replacement therapy, and calcium and vitamin D supplementation.

PMID- 8548262
TI  - The management of combined skeletal and arterial injuries of the lower extremity.
AB  - Combined skeletal, soft-tissue, and arterial injuries in lower extremity trauma
      are relatively common. Controversy has surrounded the priority of management of
      these limb- and life-threatening injuries. There are proponents for initial
      skeletal stabilization, and an equal number in favor of initial
      revascularization. The management of a multiply-traumatized patient with an
      ischemic limb and other life-threatening injuries, and a literature review, are
      presented to examine some of the issues and describe the use of vascular shunts
      as a method for rapid temporary revascularization of a damaged limb.

PMID- 8548263
TI  - Treatment of intercondylar and supracondylar distal femur fractures using the GSH
      supracondylar nail.
AB  - From April 1990 to August 1994, the GSH supracondylar intramedullary nail (Smith
      & Nephew/Richards, Memphis, Tennessee) was used to treat 23 supracondylar femur
      fractures in 22 patients. Nineteen of the 23 fractures were highly comminuted and
      intra-articular. Fifteen patients with 16 fractures were followed up to healing
      or declaration of nonunion for an average of 10 months. All fractures were
      treated with direct reduction through a median parapatellar incision. Fixation of
      the intercondylar fractures was with 6.5-mm cannulated screws, and the GSH nail
      was then inserted between the screws to secure the articular segment to the
      shaft. Fifteen of the 16 fractures healed (94%) with excellent and good results
      at an average of 3.3 months. Initial postoperative fracture reduction was
      maintained in all patients until union, as shown by follow-up radiographs.
      Thirteen of the 16 patients were treated with immediate continuous passive motion
      of the knee. Average knee range-of-motion was 109 degrees. Complications included
      1 nonunion, 1 delayed union, 1 hardware failure secondary to premature full
      weight-bearing, and 1 patient with impingement of the nail in the intercondylar
      notch. This impingement resolved with removal of the nail after fracture healing.
      The GSH supracondylar intramedullary nail is an excellent alternative for the
      treatment of supracondylar and intercondylar femur fractures.

PMID- 8548265
TI  - Conservative treatment modalities for back pain.

PMID- 8548264
TI  - Metaphyseal dissociation fractures of the proximal tibia. An analysis of
      treatment and complications.
AB  - A study was done of 44 metaphyseal dissociation fractures of the proximal tibia
      in 42 patients (27 men and 15 women, aged 22 to 77 years; mean, 42 years). Follow
      up ranged from 6 months to 4 years. There were 2 study groups: a retrospective
      group (group 1, 22 fractures) given a variety of treatments ranging from casts to
      dual plates, and a prospective group (group 2, 22 fractures) treated by combining
      external fixation and optional minimal internal fixation. There were 12
      comminuted fractures in group 1 and 20 in group 2 (P < 0.01). All fractures
      eventually healed, with an average healing time in group 1 of 3.8 months, and 5.3
      months in group 2. There was one delayed union in group 2. Results were graded
      from poor to excellent, based on pain, range-of-motion, and malunion. There were
      6 poor and 4 fair results in group 1, and no poor and 3 fair results in group 2.
      Complications included 6 deep infections, 5 in group 1 (1 requiring a free-flap
      procedure); and 1 pin-tract infection resulting in septic arthritis in group 2.
      There were 7 gastrocnemius flaps required in group 1, and 1 in group 2. The
      results of this study suggest that patients treated with external fixation had
      better results with less infection and soft-tissue complications than those
      treated with conventional internal fixation.

PMID- 8548266
TI  - Refractory pelvic stress fracture in a female long-distance runner.
AB  - Stress fractures of the pelvis are uncommon. They tend to occur in female long
      distance runners. We present the case of a female jogger with amenorrhea and
      osteoporosis who presented with left hip and groin pain. An initial bone scan
      yielded normal results. Symptoms persisted and subsequent plain radiographs and a
      repeat bone scan revealed evidence of public rami stress fractures. She developed
      a delayed union that ultimately healed with an electrical bone growth stimulator.

PMID- 8548267
TI  - Beware of absent femoral pulse (or how to prevent major complications after minor
      procedures).

PMID- 8548269
TI  - A 9-year-old girl with a bowed right forearm 6 months after a fracture.
AB  - The following case is presented to illustrate the roentgenographic and clinical
      findings of a condition of interest to the orthopedic surgeon. Initial history,
      physical findings, and roentgenographic examinations are found on the first page.
      The final clinical and roentgenographic differential diagnoses are presented on
      the following pages.

PMID- 8548268
TI  - An Unusual fracture dislocation pattern in a patient with an os lunatotriquetrum.
AB  - Lunatotriquentral fusions are fairly uncommon. An unusual fracture dislocation
      pattern from a severe wrist injury in the presence of a congenital os
      lunatotriquetrum is presented. The authors suggest anomolous carpal mechanics
      secondary to the carpal coalition as the reason for the unusual fracture pattern.
      Restoration of the pre-injury carpal orientation and internal fixation yielded a
      satisfactory result.

PMID- 8548270
TI  - A 23-year-old man with pain and swelling in his left thumb.
AB  - The following case is presented to illustrate the roentgenographic and clinical
      findings of a condition of interest to the orthopedic surgeon. Initial history,
      physical findings, and roentgenographic examinations are found on the first page.
      The final clinical and roentgenographic differential diagnoses are presented on
      the following pages.

PMID- 8548271
TI  - Movement control. Moving the mental maps.
AB  - The brain's maps of the outside world must be shifted when the point of view
      changes. Recent experiments on cortical neurons imply that this is done by
      modulating a distributed population code for position.

PMID- 8548272
TI  - Plant morphogenesis. Life on a different plane.
AB  - Arabidopsis ton mutant cells do not make the bands of microtubules that normally
      predict cell-division planes; the planes are irregular, yet seedlings develop to
      maturity. Is cellular morphogenesis important for plant form?

PMID- 8548273
TI  - Laue crystallography. It's show time.
AB  - New crystallographic techniques make it possible to observe directly all of the
      intermediates in an enzymatic reaction. Such a series of structures can be
      combined to create a detailed movie of enzymatic catalysis.

PMID- 8548274
TI  - DNA-mismatch repair. The intricacies of eukaryotic spell-checking.
AB  - Recent work suggests that the eukaryotic system responsible for repairing DNA
      mismatches, and so correcting replication errors, is more complex than was
      thought; its multiple components have many cellular functions.

PMID- 8548275
TI  - Antigen-presenting cells. Professionals and amateurs.
AB  - Professional antigen-presenting cells, notably dendritic cells, play a key role
      in stimulating naive T cells--but nonprofessional antigen-presenting cells, such
      as fibroblasts, may also contribute to this process.

PMID- 8548276
TI  - Synaptic transmission. Kinetics of synaptic-vesicle recycling.
AB  - The kinetics of different steps in synaptic-vesicle recycling, including
      exocytosis, internalization and repriming, have recently been estimated in
      various types of living cell.

PMID- 8548277
TI  - Cell polarity. The importance of being polar.
AB  - Cell polarization is often accompanied by cytoskeletal rearrangements. Two
      signalling proteins, a GTPase and a kinase, are required for both actin and
      microtubule rearrangements. Are these two systems coupled?

PMID- 8548278
TI  - Recombination. Pieces of the site-specific recombination puzzle.
AB  - Understanding how nucleoprotein complexes interact with specific DNA sequences
      has come closer with structural and mechanistic studies of the interaction
      between the recombination enzyme resolvase and DNA.

PMID- 8548279
TI  - Hearing. Asking the auditory cortex the right question.
AB  - Recordings in different parts of the cortex are beginning to reveal how animal
      communication calls are analyzed by the brain.

PMID- 8548280
TI  - Human evolution. Y-chromosome clues to human ancestry.
AB  - The case for a recent expansion of modern humans from Africa has been
      strengthened by the finding of monomorphism in part of a Y-linked gene,
      consistent with the low variability seen in human mitochondrial DNAs.

PMID- 8548281
TI  - Gamma delta T cells. T cells with B-cell-like recognition properties.
AB  - Recent results suggest there are fundamental differences in antigen recognition
      by alpha beta and gamma delta T-cell receptors, which might underlie possible
      differences in function between these two types of T cell.

PMID- 8548282
TI  - Protein-protein interactions. Putting the pieces together.
AB  - What do the recently determined crystal structures of 14-3-3 proteins and of a
      complex between part of the protein kinase Raf and the Ras-related protein Rap
      tell us about how 14-3-3 and Ras regulate the function of Raf?

PMID- 8548283
TI  - Cell cycle. The NIMA kinase joins forces with Cdc2.
AB  - The NIMA and Cdc2 protein kinases cooperate to regulate mitosis in Aspergillus
      nidulans. NIMA-related pathways have now begun to emerge in higher eukaryotes.

PMID- 8548284
TI  - Human visual cortex. Progress and puzzles.
AB  - A wealth of data is now available on the functional organization of the human
      visual cortex. Caution is necessary in basing interpretations of such data on
      information gained from studies of the monkey visual cortex.

PMID- 8548285
TI  - Pattern of ecological shifts in the diversification of Hawaiian Drosophila
      inferred from a molecular phylogeny.
AB  - BACKGROUND: The endemic Hawaiian drosophilids, a unique group that are remarkable
      for their diversity and rapid proliferation, provide a model for analysis of the
      process of insular speciation. Founder events and accompanying random drift,
      together with shifts in sexual selection, appear to explain the dramatic
      divergence in male morphology and mating behaviour among these flies, but these
      forces do not account for their spectacular ecological diversification into a
      wide array of breeding niches. Although recognized as contributing to the success
      of this group, the precise role of adaptive shifts has not been well defined.
      RESULTS: To delineate the pattern of ecological diversification in the evolution
      of Hawaiian Drosophila, we generated a molecular phylogeny, using nucleotide
      sequences from the yolk protein gene Yp1, of 42 endemic Hawaiian and 5
      continental species. By mapping ecological characters onto this phylogeny, we
      demonstrate that monophagy is the primitive condition, and that decaying leaves
      were the initial substrate for oviposition and larval development. Shifts to
      decaying stems, bark and tree fluxes followed in more derived species. By
      plotting female reproductive strategies, as reflected in ovarian developmental
      type, on the molecular tree, we also demonstrate a phylogenetic trend toward
      increasing fecundity. We find some statistical support for correlations between
      ecological shifts and shifts in female reproductive strategies. CONCLUSIONS:
      Because of the short branches at the base of the phylogram, which lead to
      ecologically diverse lineages, we conclude that much of the adaptive radiation
      into alternate breeding substrates occurred rapidly, early in the group's
      evolution in Hawaii. Furthermore, we conclude that this ecological divergence and
      the correlated changes in ovarian patterns that adapt species to their ecological
      habitats were contributing factors in the major phyletic branching within the
      Hawaiian drosophilid fauna.

PMID- 8548287
TI  - The search for DNA homology does not limit stable homologous pairing promoted by
      RecA protein.
AB  - BACKGROUND: The basic molecular mechanisms that govern the search for DNA
      homology and subsequent homologous pairing during genetic recombination are not
      understood. RecA is the central homologous recombination protein of Escherichia
      coli; because several RecA homologues have been identified in eukaryotic cells,
      it is likely that the mechanisms employed by RecA are conserved throughout
      evolution. Analysis of the kinetics of the homologous search and pairing
      reactions catalyzed by RecA should therefore provide insights of general
      relevance into the mechanisms by which macromolecules locate, and interact with,
      specific DNA targets. RESULTS: RecA forms three-stranded synaptic complexes with
      a single-stranded oligonucleotide and a homologous region in duplex DNA. The
      kinetics of this initial pairing reaction were characterized using duplex DNA
      molecules of various concentrations and complexities containing a single target
      site, as well as various concentrations of homologous single-stranded
      oligonucleotides. The formation of the synaptic complex follows apparent second
      order reaction kinetics with a rate proportional to the concentrations of both
      the homologous single-stranded oligonucleotide and the target sites within the
      duplex DNA. The reaction rate is independent of the complexity of duplex DNA in
      the reaction. We propose a kinetic scheme in which the RecA-single-stranded DNA
      filament interacts with duplex DNA and locates its target in a relatively fast
      reaction. We also suggest that complex conformational changes occur during the
      subsequent rate-limiting step. CONCLUSIONS: We conclude that, during the
      formation of synaptic complexes by RecA, the search for homology is not rate
      limiting, and that the iteration frequency of the search is around 10(2)-10(3) s
      1. This value agrees well with what has been calculated as the minimum number for
      such a frequency in genome-wide searches, and limits the possible structures
      involved in the search for homology to those involving very soft (low energy)
      interactions. Furthermore, from the order of the reaction at the DNA
      concentrations found in eukaryotic nuclei, and the rate constant of the overall
      reaction, we predict that the search for homology is also not the rate-limiting
      step in the genome-wide searches implicated in meiosis and in gene targeting.

PMID- 8548286
TI  - Pre-B-cell development in the absence of lambda 5 in transgenic mice expressing a
      heavy-chain disease protein.
AB  - BACKGROUND: Heavy-chain diseases (HCDs) are human lymphoproliferative neoplasias
      that are characterized by the secretion of truncated immunoglobulin heavy chains
      devoid of light chains. We have previously proposed--by analogy to the process by
      which mutated growth factor receptors can be oncogenic--that because the genetic
      defects in HCDs result in the production of abnormal membrane-associated heavy
      chains lacking an antigen-binding domain, these abnormal B-cell antigen receptors
      might engage in ligand-independent signalling. Normal pre-B-cell development
      requires the presence of the pre-B-cell receptor, formed by the association of mu
      heavy chains with two polypeptides--so-called surrogate light chains, Vpre-B and
      lambda 5--that are homologous to the variable and constant portions of
      immunoglobulin light chains, respectively. To assess whether amino-terminal
      truncation of membrane-associated heavy chains results in their constitutive
      activation, we have examined the ability of a HCD-associated mu protein to
      promote pre-B-cell development in transgenic mice. RESULTS: When the mu HCD
      transgene is introduced into SCID mice, CD43- pre-B cells develop normally. To
      determine whether this pre-B-cell development requires surrogate light chains, we
      backcrossed mice expressing full-length or truncated mu transgenes with lambda 5
      deficient mice. Our results show that the truncated heavy chain, but not the
      normal chain, is able to promote pre-B-cell development in the absence of lambda
      5. We also show that truncated mu chains spontaneously aggregate at the surface
      of bone marrow cells. CONCLUSIONS: Expression of the truncated mu heavy chain
      overrides a tightly controlled step of pre-B-cell development, which strongly
      suggests that a constitutive signal is delivered by the truncated mu chain
      disease protein. The self-aggregation of mu chain disease proteins might account
      for this constitutive activation. We conclude that amino-terminal truncation of
      heavy chains could play a role in the genesis of HCD neoplasia if it occurs at an
      appropriate stage of B-cell differentiation, namely in a mature B cell.

PMID- 8548288
TI  - Identification and partial characterization of a domain in CFTR that may bind
      cyclic nucleotides directly.
AB  - BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) is a
      chloride channel that is activated by cAMP-dependent phosphorylation. CFTR
      channel activity is also stimulated by cGMP-dependent protein kinase and protein
      kinase C. RESULTS: Here, we show that CFTR channel activation by cGMP may also
      occur directly. In oocytes from one-third of Xenopus donors, the activation of
      CFTR by cGMP averaged 87% of the level achieved by cAMP. The currents activated
      by either cyclic nucleotide displayed similar current-voltage relationships,
      kinetics, pharmacology and halide selectivity. Sequential stimulation by cAMP and
      cGMP was not additive, suggesting that both cyclic nucleotides activate the same
      channel; cGMP was one order of magnitude more potent than cAMP, and its action
      was insensitive to protein kinase inhibitors. Analysis of the amino-acid sequence
      of CFTR revealed a domain in the amino-terminal portion of the third cytoplasmic
      loop that resembles a class of cyclic-nucleotide-binding domains related to that
      of the catabolite-gene activator protein, CAP. Two CFTR residues in this domain-
      Val397 and Lys420--were identified which, when changed to alanine, altered the
      response to cGMP independently of the response to cAMP. CONCLUSIONS: We conclude
      that direct cyclic nucleotide binding may play a role in channel gating of CFTR.
      The cGMP-binding domain may provide a useful target for pharmacologic
      intervention in cystic fibrosis.

PMID- 8548289
TI  - Role of the regulatory domain of the EGF-receptor cytoplasmic tail in selective
      binding of the clathrin-associated complex AP-2.
AB  - BACKGROUND: After stimulation of a cell by the mitogenic epidermal growth factor
      (EGF), the EGF receptor (EGF-R) is cleared from the cell surface in order to turn
      off receptor signaling. This internalization is mediated via clathrin-coated pits
      and coated vesicles, and ultimately the receptors are delivered to the lysosome
      and destroyed. It is believed that clathrin-associated protein complexes or
      adaptors (APs) link the entrapment of EGF-R and other nutrient and growth-factor
      receptors to the formation of the clathrin-coated pit. Two classes of APs are
      known--AP-2, found at the plasma membrane, and AP-1, found in the trans-Golgi
      network. Activated EGF-R associates with AP-2s at the plasma membrane, but the
      mechanism responsible for this association is not known. Here, we investigate, in
      vivo and in vitro, three aspects of the interaction between APs and EGF-R:
      firstly, we ask whether EGF-R at the plasma membrane distinguishes between AP-1
      and AP-2; secondly, we ask which part of the receptor's cytoplasmic tail is
      responsible for binding; finally, we ask whether autophosphorylation by EGF-R is
      essential for the interaction. RESULTS: We demonstrate that EGF-R displays a
      selective association for AP-2 over AP-1 in vivo, and that this preferential
      interaction can also be detected using surface plasmon resonance in vitro. Using
      a truncated mutant and a kinase-dead mutant of EGF-R, we show that the regulatory
      domain of the cytoplasmic tail is essential for the recruitment of AP-2 in vivo
      and that this domain is required for association between purified AP-2 and EGF-R
      in vitro. Finally, we demonstrate, in vivo and in vitro, that tyrosine auto
      phosphorylation by the receptor is not an essential pre-condition for the
      recruitment of AP-2. CONCLUSIONS: EGF-R binds selectively to AP-2s, and the
      regulatory domain of its cytoplasmic tail is required for this interaction. The
      lack of correlation between receptor autophosphorylation and AP-2 recruitment
      suggests that activation of the EGF-R kinase stimulates endocytosis by the
      phosphorylation of a factor distinct from EGF-R itself, as also proposed by
      others based on experiments measuring receptor traffic and entrapment.

PMID- 8548290
TI  - The chk1 pathway is required to prevent mitosis following cell-cycle arrest at
      'start'.
AB  - BACKGROUND: The G2-M-phase transition is controlled by cell-cycle checkpoint
      pathways which inhibit mitosis if previous events are incomplete or if the DNA is
      damaged. Genetic analyses in yeast have defined two related, but distinct,
      pathways which prevent mitosis--one which acts when S phase is inhibited, and one
      which acts when the DNA is damaged. In the fission yeast Schizosaccharomyces
      pombe, many of the gene products involved have been identified. Six 'radiation
      checkpoint' (rad) gene products are required for both the S-M and DNA-damage
      checkpoints, whereas Chk1, a putative protein kinase, is required only for the
      DNA-damage checkpoint and not for the S-M checkpoint following the inhibition of
      DNA synthesis. RESULTS: We have genetically defined a third mitotic control
      checkpoint pathway in fission yeast which prevents mitosis when passage through
      'start' (the commitment point in G1) is compromized. In cycling cells arrested at
      start, mitosis is prevented by a Chk1-dependent pathway. In the absence of Chk1,
      G1 cells attempt an abortive mitosis with a 1C DNA content without entering S
      phase. Similar results are seen in the absence of Rad17, a typical example of a
      rad gene product. CONCLUSIONS: Genetic dissection of checkpoints in
      logarithmically growing fission yeast has identified a pathway that couples
      mitosis to correct passage through start. This pathway is related to the DNA
      structure check-points which ensure that mitosis is dependent on the completion
      of replication and the integrity of the DNA. We propose that all three mitotic
      control checkpoints monitor distinct DNA or protein structures at different
      stages in the cell cycle.

PMID- 8548291
TI  - Activation of ternary complex factor Elk-1 by stress-activated protein kinases.
AB  - BACKGROUND: The mammalian response to stress results in the activation of stress
      activated protein kinases (also known as cJun N-terminal kinases; SAPKs or JNKs),
      which are a sub-group of the mitogen-activated protein (MAP) kinase family. The
      SAPKs are involved in the upregulation of activity of the transcription factor AP
      1 by post-translational modification of two of its components, cJun and ATF2. AP
      1 activity can also be elevated by increased expression of the Fos protein, a
      further AP-1 component. Elk-1 (also called p62TCF), a transcription factor
      involved in the induction of the expression from the c-fos promoter through the
      promoter's serum response element, is known to be activated as a result of
      phosphorylation by the MAP kinases ERK1 and ERK2. However, induction of c-fos
      expression in response to noxious agents takes place in the absence of ERK
      activation. We therefore investigated whether SAPKs similarly upregulate c-fos
      expression by phosphorylating Elk-1. RESULTS: Elk-1 is activated in response to
      stimuli other than mitogenic signals. Both p46SAPK and p54SAPK interact
      physically with, and phosphorylate, Elk-1. The capacity of Elk-1 to form a
      ternary complex with serum response factor in vitro is thereby elevated. In vivo,
      selective activation of SAPKs stimulates formation of the ternary complex
      containing Elk-1, serum response factor and the serum response element, and
      enhances Elk-1-dependent transcription. Expression of the SAPK upstream-activator
      kinase, MEKK1, induces SAPK activation and c-fos transcription in the absence of
      ERK activity. Phosphopeptide mapping of Elk-1 phosphorylated with p46SAPK or
      p54SAPK reveals Ser383, a residue critical for ternary complex formation and
      transcriptional activation, to be the major phosphorylation site. CONCLUSION: Elk
      1 responds to stress-induced, as well as mitogenic, signals by stimulating c-fos
      transcription through the serum response element. Phosphorylation of Elk-1 by
      SAPKs and the ensuing expression of Fos protein thus constitutes an additional
      mechanism by which cells can upregulate AP-1 activity in response to stress.

PMID- 8548292
TI  - Charting of Jun family member proteins in the rat forebrain and midbrain:
      immunocytochemical evidence for a new Jun-related antigen.
AB  - Immunocytochemistry was used to localize members of the Jun family of immediate
      early genes in the forebrain and midbrain of non-stimulated male rats. Antibodies
      against specific peptide sequences of c-Jun (Ab-1 and Ab-2 from Oncogene Science)
      and against expressed proteins of JunB and JunD (both from Dr. R. Bravo) revealed
      widespread and unique distributions for each of these antigens. Charts were made
      of the distribution of each antigen, and extensive comparisons were made of
      previous results obtained using in situ hybridization to localize mRNAs for c
      jun, junB and junD. Our results indicate a generally favorable comparison between
      immunoreactivity and distribution of mRNAs for JunB and JunD, but in the case of
      c-Jun, immunoreactivity and mRNA were comparable only with the Ab-1 antibody.
      Indeed, the immunocytochemical distribution of the antigen recognized by the c
      Jun Ab-2 antibody was distinctly different from that of the other Jun proteins or
      mRNAs in the rat brain. This antibody (Ab-2) recognized a nuclear protein found
      extensively in the caudate-putamen, nucleus accumbens, layer II of the olfactory
      tubercle, the central nucleus of the amygdala, and the lateral division of the
      bed nucleus of the stria terminalis. Scattered labeled nuclei were found in a few
      other forebrain structures. Within the caudate-putamen, immunoreactivity was
      restricted to the matrix compartment, as determined by immunostaining of adjacent
      sections with the matrix-marker calbindin D28k. Western blots of caudate-putamen
      demonstrated that this antibody recognized a protein doublet of molecular masses
      approximately 37 and 34 kDa, distinct from the molecular masses of c-Jun, JunB
      and JunD. This unique neuroanatomical distribution and molecular mass suggests
      that this antibody recognizes a previously undescribed Jun-related antigen.

PMID- 8548293
TI  - Action potential-dependent output of 5-hydroxytryptamine in the anaesthetized rat
      amygdalopiriform cortex is strongly inhibited by tonic 5-HT1B-receptor
      stimulation.
AB  - The output of 5-hydroxytryptamine (5-HT) from the amygdalopirifrom cortex has
      been measured in anaesthetized rats using intracerebral microdialysis followed by
      HPLC analysis. Basal output overall of 5-HT was 2.558 +/- 0.351 fmol/20 min
      sampling period. Application of the 5-HT antagonist metergoline through the
      dialysis probe resulted in a greater than 10-fold increase in the overflow of 5
      HT. The major portion of this increase occurred in the range 1-3 microM
      metergoline, and was completely attenuated by inclusion of tetrodotoxin. More
      specific 5-HT antagonists, such as cyanopindolol, also enhanced output, but to a
      lesser extent. The pharmacological profile of the receptors mediating the effect
      was similar to that of the 5-HT1B type, which are often found presynaptically on
      5-HT-containing nerve terminals. Other drugs were also capable of altering the
      output of 5-HT; in particular, muscimol reduced dialysate 5-HT content, while
      propranolol increased it. The 5-HT uptake inhibitor citalopram significantly
      increased the overflow of 5-HT, but only by about 80% above basal levels. It is
      concluded that the release of 5-HT from the rat amygdalopiriform cortex in vivo
      is tightly restricted due to activation of 5-HT1B receptors. Small alterations in
      such activation, however, can lead to large changes in 5-HT output, suggesting a
      possible mechanism by which neurotransmission through the amygdalopiriform cortex
      may become unstably amplified. These results may be of significance to the
      generation of epileptic activity in the amygdala or piriform cortex.

PMID- 8548294
TI  - Transient brain ischemia in rabbits: the effect of omega-conopeptide MVIIC on
      hippocampal excitatory amino acids.
AB  - Neurologic injury that occurs after ischemia results from a cascade of events
      involving the release of various endogenous neurotoxins. A portion of the release
      of excitatory neurotransmitters is calcium dependent and may be attenuated by
      administration of calcium channel blockers. Using an in vivo model of ischemia,
      we studied the effects of omega-conopeptide MVIIC, a voltage-sensitive calcium
      channel blocker, and hypothermia (32 degrees C) on hippocampal glutamate and
      aspartate release in the peri-ischemic period. Thirty-four New Zealand white
      rabbits of either sex were anesthetized with halothane, intubated, and
      mechanically ventilated. Monitored variables included blood gases, mean arterial
      blood pressure, and the electroencephalogram. Microdialysis catheters were
      transversely inserted through the anterior portion of the dorsal hippocampus and
      perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min.
      After stabilization period, animals were randomly assigned to one of the
      following groups: Control group (n = 8), 10 microM omega-conopeptide MVIIC group
      (n = 7), 100 microM omega-conopeptide MVIIC group (n = 7), Hypothermia group (n =
      6; cranial temperature = 32 degrees C), and omega-conopeptide MVIIC + hypothermia
      group (n = 6; 100 microM omega-conopeptide MVIIC and cranial temperature 32
      degrees C). All the rabbits were subjected to 10 minutes of global cerebral
      ischemia produced by neck tourniquet inflation combined with hypotension during
      halothane anesthesia. Conopeptide MVIIC was administered in the artificial
      cerebrospinal fluid used to perfuse the microdialysis catheter. In control
      animals, ischemia caused a significant increase in glutamate (9.7 fold) and
      aspartate (11.3 fold) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8548295
TI  - Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia
      in rats.
AB  - We assessed the effect of interleukin-6 (IL-6) in the brain on nociception by
      using the hot-plate test in rats. Recombinant human IL-6 (rhIL-6, 30 pg-300 ng)
      was microinjected into the lateral cerebroventricle (LCV) and the paw-withdrawal
      latency was then measured for 60 min after injection. RhIL-6 at 300 pg reduced
      the paw-withdrawal latency at 15 min after injection. Further increase of rhIL-6
      doses to 3, 30 and 300 ng resulted in the decreased paw-withdrawal latency at 15
      and 30 min. Although the peak responses observed at 3-300 ng did not differ
      significantly, the time taken for recovery tended to be longer with increasing
      doses. The rhIL-6 (30 ng)-induced reduction of the paw-withdrawal latency was
      completely blocked by the co-injection of either Na salicylate (30 ng, LCV) or
      alpha-melanocyte stimulating hormone (30 ng, LCV), an anti-cytokine substance.
      However, it was not affected by the co-injection of IL-1 receptor antagonist (30
      ng, LCV) which had been previously shown to be able to block IL-1 beta-induced
      hyperalgesia. These findings indicate that IL-6 in the brain induces hyperalgesia
      by its prostanoids-dependent action in rats. The hyperalgesic action of central
      IL-6 thus does not appear to depend on the action of IL-1.

PMID- 8548296
TI  - Glutamate enhances the adenylyl cyclase-cAMP system-induced beta-endorphin
      secretion and POMC mRNA expression in rat hypothalamic neurons in culture: NMDA
      receptor-mediated modulation.
AB  - L-Glutamate, a major excitatory amino acid of the central nervous system, plays
      important roles as neurotransmitter and neuromodulator in the brain. Increasing
      evidence suggests that glutamate may also involve in the regulation of the
      neuroendocrine system at the hypothalamus. Employing long term monolayer
      hypothalamic cell cultures prepared from neonatal rats, we reported here that
      whereas glutamate significantly enhanced forskolin-, or N6,2'-O
      dibutyryladenosine-3'5'-cyclic monophosphate [(Bu)2cAMP]-stimulated
      immunoreactive (ir)-beta EP release from cultures treated daily for 4 consecutive
      days, the excitatory amino acid alone produced little effect. This potentiation
      of glutamate was time-related and dose-dependent with an Emax value of the amino
      acid being approximately 50 microM; at this concentration glutamate augmented ir
      beta EP secretion about 1.8 times (P < 0.05) that induced by 2 microM forskolin
      alone. Similar effects were also observed for POMC mRNA levels in cultures
      subjected to 6 h of the above treatment regime. This potentiating effect of
      glutamate appears to be mediated specifically through NMDA receptor as it can be
      mimicked by NMDA but not by kainic acid or quisqualic acid, and blocked by the
      NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV), but not by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), a non-NMDA glutamate receptor antagonist.
      Interestingly, glutamate was found not to enhance high doses of forskolin (10
      microM) or (Bu)2cAMP (100 microM) stimulated beta EP release and POMC mRNA levels
      in hypothalamic cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8548297
TI  - Nitric oxide synthase inhibitor blocks light-induced phase shifts of the
      circadian activity rhythm, but not c-fos expression in the suprachiasmatic
      nucleus of the Syrian hamster.
AB  - Circadian rhythms in mammals are entrained to the environmental light cycle by
      daily adjustments in the phase of the circadian pacemaker located in the
      suprachiasmatic nuclei (SCN) of the hypothalamus. Brief exposure of hamsters
      maintained under constant darkness to ambient light during subjective nighttime
      produces both phase shifts of the circadian activity rhythm and characteristic
      patterns of c-fos protein (Fos) immunoreactivity in the SCN. In this study, we
      demonstrate that light-induced phase shifts of the circadian activity rhythm are
      blocked by intracerebroventricular (i.c.v.) injection of the competitive nitric
      oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not
      by the inactive isomer, D-NAME. The effects of L-NAME are reversible and dose
      related, and are countered by co-injection of arginine, the natural substrate for
      NOS. While effects on behavioral rhythms are pronounced, similar treatment does
      not alter the pattern of light-induced Fos immunoreactivity in the SCN. These
      results suggest that nitric oxide is a component of the signal transduction
      pathway that communicates photic information to the SCN circadian pacemaker, and
      that nitric oxide production is either independent of, or downstream from,
      pathways involved in induction of c-fos expression.

PMID- 8548298
TI  - Nerve growth factor facilitates conditioned taste aversion learning in normal
      rats.
AB  - Chronic intracerebroventricular (i.c.v.) infusion of 3.2 micrograms/day of nerve
      growth factor (NGF) in normal rats elevated choline acetyltransferase (ChAT)
      activity of the striatum, medial septum, and basal forebrain and improved
      performance of a conditioned taste aversion (CTA) task. Relative to bovine serum
      albumin (BSA) or Cytochrome C treatments, NGF treatment facilitated acquisition
      and prolonged extinction of a lithium chloride (LiCl)-induced saccharin aversion.
      This facilitation was evident at saccharin/LiCl intervals ranging up to 1 h.
      Also, NGF treatment did not increase reactivity to LiCl-induced illness and
      neither shifted detection thresholds nor altered hedonic reactions to taste
      stimuli, indicating that NGF did not produce simple changes in sensory function.
      NGF treatments that elevate ChAT also facilitate memory of CTA in normal, adult
      rats.

PMID- 8548299
TI  - NGF-mediated synaptic sprouting in the cerebral cortex of lesioned primate brain.
AB  - In the present study, coronal brain sections of cortically devascularized non
      human primates (Cercopithecus aethiops) were used to assess the lesion-associated
      synaptic loss, and the effect of exogenous nerve growth factor (NGF) in
      preventing or reversing this neurodegeneration. The sections were immunolabeled
      with antibodies against the synaptic marker protein synaptophysin (SYN), as well
      as choline acetyltransferase (ChAT) and parvalbumin (PV) markers that identify
      cholinergic neurons and interneurons, respectively. We found that, compared to
      sham-operated animals, in the lesioned vehicle treated animals SYN
      immunoreactivity near the lesioned site in the frontoparietal cortex was
      decreased by 31%. Similarly, corrected optical density values of immunostained
      sections specific for ChAT in the nucleus basalis of Meynert (ipsilateral to the
      lesion) decreased by 20% and PV-immunoreactive neurons near the lesion decreased
      by 47%. In contrast, NGF-treated lesioned animals showed levels of SYN, ChAT, and
      PV immunoreactivity similar to sham controls. These results are consistent with
      previous studies and support the view that NGF may not only prevent
      neurodegenerative changes after neocortical infarction by protecting vulnerable
      neurons, but also is capable of inducing sprouting and synaptogenesis.

PMID- 8548300
TI  - Ultrastructural damage and neuritic beading in cold-stressed spinal neurons with
      comparisons to NMDA and A23187 toxicity.
AB  - While exposure of cultured spinal neurons to mild hypothermia provides some
      protection from physical trauma (dendrotomy), profound cooling (< 17 degrees C)
      causes unrelated neuronal injury and death, which can be prevented by treatment
      with NMDA receptor antagonists. To investigate the mechanism of hypothermic
      neuronal injury we examined the ultrastructure of cultured spinal neurons after 2
      h of cooling to 17 degrees C or 10 degrees C, with or without the presence of the
      NMDA receptor antagonist D-2-amino-5-phosphonovalerate, and with or without
      rewarming to 37 degrees C. These groups were compared to cultures exposed to NMDA
      or to the calcium ionophore A23187. Patterns of ultrastructural change, involving
      cytoskeletal disruption, mitochondrial abnormalities and vacuolization of the
      cytoplasm, suggest a common mechanism of injury in all treatment groups,
      involving an elevation of intracellular calcium. Some neurons exposed to
      hypothermia, NMDA or ionophore developed beaded dendrites. Microtubules were
      fragmented in varicosities but not in the intervening constrictions; other
      organelles were largely excluded from the constrictions. Varicosities may form
      when organelles and cytoplasm accumulate as the result of disruption of transport
      and membrane stabilizing proteins by proteases activated by calcium influx via
      NMDA mediated channels. The periodic nature of the swellings may reflect
      inherently discontinuous distribution of molecular subunits of the cytoskeleton.

PMID- 8548301
TI  - 3,4-Diaminopyridine-evoked noradrenaline release in rat hippocampal slices:
      facilitation by endogenous or exogenous nitric oxide.
AB  - The involvement of nitric oxide (NO) in the evoked release of noradrenaline (NA)
      was studied in rat hippocampal slices preincubated with [3H]NA and stimulated
      with 3,4-diaminopyridine (3,4-DAP; 200 microM) for 2 min. The 3,4-DAP-evoked
      [3H]overflow was enhanced by the NO synthase substrate L-arginine, but not by D
      arginine; it was reduced by the NO synthase inhibitor NG-nitro-L-arginine, which
      also antagonized the effects of L-arginine. The corresponding nitro derivative of
      D-arginine was inactive and unable to block the effects of L-arginine. Also drugs
      known to produce NO in-vitro, like sodium nitroprusside (SNP), 3-morpholino
      sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP) enhanced the 3,4
      DAP-evoked NA release. The NO scavenger hemoglobin showed no significant effects
      when given alone, but reduced or abolished, respectively, the facilitatory
      effects of SNP, or SNAP and L-arginine. The cyclic GMP derivatives 8-Br-cGMP and
      Sp-8-p-chlorophenylthioguanosine-3',5'-cyclic monophosphorothioate (Sp-8-pCPT
      cGMPS) also acted facilitatory, whereas the corresponding Rp-enantiomer of the
      latter compound was inactive, but antagonized the effect of Sp-8-pCPT-cGMPS. NA
      release evoked by 3,4-DAP (10 microM) from rat hippocampus synaptosomes was not
      affected by L-arginine or NG-nitro-L-arginine but slightly increased by SNAP and
      Sp-8-pCPT-cGMPS. Antagonists at NMDA, non-NMDA and metabotropic glutamate
      receptors neither affected the 3,4-DAP-evoked NA release nor the facilitatory
      effect of L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8548302
TI  - Isolation and culture of human brain microvessel endothelial cells for the study
      of blood-brain barrier properties in vitro.
AB  - A simplified protocol for isolating brain microvessel endothelial cells (BMEC)
      from human cortex and culturing them on a thick collagen plug is described. This
      method results in the establishment of monolayers of BMEC that retain numerous
      properties indicative of the blood-brain barrier (BBB) phenotype, such as
      elevated transendothelial electrical resistance, attenuated paracellular flux of
      sucrose, peripheral actin filament distribution and asymmetric localization of
      the efflux peptide, P-glycoprotein, to the apical (luminal) BMEC surface. The
      novel 3-dimensional nature of this model system renders it ideally suitable for
      assaying such varied aspects of BBB physiology as solute transport, pathogen
      penetrance, leukocyte infiltration and tumor metastasis into the brain. Moreover,
      the fact that the system is derived from human brain allows for the study of
      pathogenetic mechanisms that may only be operative in humans.

PMID- 8548303
TI  - NBQX, an improved non-NMDA antagonist studied in retinal ganglion cells.
AB  - The quinoxaline derivative, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo (F)
      quinoxaline (NBQX), significantly reduced the currents evoked by exogenous
      application of quisqualate (QQ), kainate (KA) and alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) when applied to ganglion cells, using
      whole-cell recording in a slice preparation of the tiger salamander retina. A
      comparison between NBQX and CNQX indicates that NBQX is more effective in
      blocking AMPA receptors. Also, at up to 10 microM, NBQX has no effect on NMDA
      induced currents. Thus at this concentration, NBQX shows no affinity for the
      glycine binding site of NMDA receptors. For this reason, NBQX is preferred over
      CNQX for a more effective and selective antagonism toward non-NMDA receptors.

PMID- 8548304
TI  - NADPH-diaphorase expression in neurons and glia of the normal adult rat retina.
AB  - In the rat retina, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH
      d) staining has been described previously in a population of amacrine cells, most
      of which were located in the inner nuclear layer. In the present study, a number
      of parameters such as the nature of the fixative, the time of fixation and
      photointensification were optimised to obtain the strongest possible reaction for
      this enzyme. As a result, a very different staining pattern emerged: with short
      paraformaldehyde fixation, numerous neurons (identified as a combination of
      ganglion cells and amacrines) were labelled in the ganglion cell layer, NADPH-d
      positive amacrine cells (described previously) were seen in the inner nuclear
      layer and Muller cells were labelled strongly, particularly in the inner retina.
      Glutaraldehyde fixation of the same duration resulted in the preferential
      staining of Muller cells while neurons appeared less reactive. Therefore,
      fixation conditions are a determining factor in the cellular localisation of
      NADPH-d in the rat retina. By taking fixation into account, future studies should
      gain more rigorous insights into the possible functions of this enzyme in the
      vertebrate retina.

PMID- 8548305
TI  - Microglial release of nitric oxide by the synergistic action of beta-amyloid and
      IFN-gamma.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized histopathologically by a loss of neurons and an accumulation of
      beta-amyloid plaques, neurofibrillary tangles, dystrophic neurites, and reactive
      glial cells. While most previous studies on the neurodegeneration of AD have
      focused on neuronal cells and direct beta-amyloid-mediated neurotoxicity, few
      have focused on the role of reactive glial cells in beta-amyloid-mediated
      neurotoxicity. In the present study nitric oxide release from cultured rat
      microglia was examined by exposing the cells to synthetic beta-amyloid peptides
      (beta 25-35 and beta 1-40) alone and in combination with the cytokines IFN
      alpha/beta (100 U/ml), IL-1 beta (100 U/ml), TNF-alpha (100 U/ml), TNF-beta (100
      U/ml), or IFN-gamma (10, 100, 500, or 1000 U/ml). Assessment of microglial
      release of nitric oxide was based on the colorimetric assay for nitrite in the
      culture medium and histochemistry for nitric oxide synthase. Of the cytokines
      tested, only IFN-gamma (1000 U/ml) induced nitric oxide release from microglia.
      beta 25-35 did not stimulate nitric oxide release by itself, but it did induce
      nitric oxide release when co-exposed with IFN-gamma (100, 500, and 1000 U/ml). In
      contrast, beta 1-40 did induce microglial release of nitric oxide by itself, and
      this effect was enhanced significantly by co-exposure with IFN-gamma (100 U/ml).
      These findings warrant a further investigation into the role of microglia in the
      neurodegeneration of Alzheimer's disease via nitric oxide toxicity induced by the
      synergistic action of beta-amyloid and a costimulatory factor.

PMID- 8548306
TI  - Regional and cellular expression sites of the alpha 1 subunit of GABAA receptors
      in the rat basal forebrain: a cytochemical study with glutamic acid
      decarboxylase, choline acetyltransferase, calcium-binding proteins and nitric
      oxide synthase as second markers.
AB  - Forebrain sections of adult male Wistar rats were processed for the
      immunohistochemical detection of the GABAA receptor alpha 1 subunit. Alternate
      sections were used for double-staining with antibodies to glutamic acid
      decarboxylase (GAD), choline acetyltransferase (ChAT), the calcium binding
      proteins parvalbumin (PARV), calbindin (CALB) and calretinin (CR) as well as to
      nitric oxide synthase (NOS). alpha 1 receptor subunit-immunoreactive neurons were
      found to be inhomogeneously distributed in the rat basal forebrain. Numerous
      alpha 1 subunit-immunostained neurons occupied the central part of medial septum
      and diagonal band, the whole ventral pallidum and the globus pallidus. A moderate
      number was found in the lateral septum, and only very few in the striatum and
      nucleus accumbens. Double-immunofluorescence labelling revealed an apparently
      complete co-expression of GAD-immunoreactivity in alpha 1 subunit-immunoreactive
      cells of rat basal forebrain, but only a region-dependent proportion of GAD
      immunoreactive cells showed alpha 1 subunit-immunoreactivity. Co-expression of
      PARV-immunoreactivity characterized the vast majority of the alpha 1 subunit
      immunoreactive cells in the medial septum, diagonal band, ventral pallidum and
      globus pallidus. Striatal alpha 1 subunit-immunopositive neurons appeared PARV
      immunonegative and did also not react with the other immunoreagents used in this
      study, except the GAD-antibody. CR-immunoreactivity was co-expressed in alpha 1
      subunit-immunopositive cells of the ventral lateral septal nucleus and only
      exceptionally in the ventral pallidum, where the vast majority of CR-positive
      cells was monolabelled. A small minority of ChAT-immunoreactive, but in no case
      CALB- and NOS-immunoreactive cells were found to express the alpha 1 subunit
      immunoreactivity. These findings confirm the data obtained by analyses of other
      brain regions suggesting a preferred co-existence of this GABAA receptor subunit
      with PARV and to a lesser degree with CR.

PMID- 8548307
TI  - Adenylyl cyclase activation underlies intracellular cyclic AMP accumulation,
      cyclic AMP transport, and extracellular adenosine accumulation evoked by beta
      adrenergic receptor stimulation in mixed cultures of neurons and astrocytes
      derived from rat cerebral cortex.
AB  - We have previously shown that stimulation of cortical cultures containing both
      neurons and astrocytes with the beta-adrenergic agonist isoproterenol (ISO)
      results in transport of cAMP from astrocytes followed by extracellular hydrolysis
      to adenosine [Rosenberg et al. J. Neurosci. 14 (1994) 2953-2965]. In this study
      we found that the endogenous catecholamines epinephrine (EPI) and norepinephrine
      (NE), but not dopamine, serotonin, or histamine, all at 10 microM, significantly
      stimulated intracellular cAMP accumulation, cAMP transport, and extracellular
      adenosine accumulation in cortical cultures. Detailed dose-response experiments
      were performed for NE and EPI, as well as ISO. For each catecholamine, the
      potencies in evoking intracellular cAMP accumulation, cAMP transport, and
      extracellular adenosine accumulation were similar. These data provide additional
      evidence that a single common mechanism, namely beta-adrenergic mediated
      activation of adenylyl cyclase, underlies intracellular cAMP accumulation, cAMP
      transport, and extracellular adenosine accumulation. It appears that regulation
      of extracellular adenosine levels via cAMP transport and extracellular hydrolysis
      to adenosine may be a final common pathway of neuromodulation in cerebral cortex
      for catecholamines, and, indeed, any substance whose receptors are coupled to
      adenylyl cyclase.

PMID- 8548308
TI  - Alterations in immediate-early gene proteins in the rat forebrain induced by
      acute morphine injection.
AB  - Injection of morphine (10 mg/kg) induced a complex immediate-early gene response
      in the rat forebrain, as detected with immunocytochemistry. The c-Fos protein was
      induced consistently in the dorsomedial caudate-putamen, the nucleus accumbens,
      and in midline and intralaminar nuclei of the thalamus. In some rats induction
      was also seen in the parietal and insular cortex and in lateral regions of the
      caudate-putamen. Induction was detectable, although weak, at 30 min, was maximal
      at 2 h, and was undetectable 3 h after injection. JunB was induced in the same
      regions of the caudate-putamen as found for c-Fos, but was not induced in the
      nucleus accumbens or thalamus. In the caudate-putamen, JunB induction was still
      present 3 h after injection. A considerably smaller induction of c-Jun was noted
      in the dorsomedial caudate-putamen and in deep neocortex. Expression of JunD was
      inhibited in intralaminar and midline thalamic nuclei. Increases in numbers of
      cells immunoreactive for a Jun-related antigen (Jra) were found in the caudate
      putamen and nucleus accumbens. These results indicate a complex immediate-early
      gene response to acute morphine, suggesting that morphine activates or inhibits
      specific neurons and circuits in the forebrain.

PMID- 8548309
TI  - Regional distribution of monoamine vesicular uptake sites in the mesencephalon of
      control subjects and patients with Parkinson's disease: a postmortem study using
      tritiated tetrabenazine.
AB  - The distribution of the vesicular monoamine transporter was investigated post
      mortem in the human ventral mesencephalon of control subjects (n = 7) and
      patients with Parkinson's disease (n = 4) using tritiated dihydrotetrabenzine
      binding and autoradiography. Tritiated dihydrotetrabenazine binding was
      characterized by a single class of sites with a Kd of 7 nM and a Bmax of 180
      fmol/mg of protein in the substantia nigra. Tritiated dihydrotetrabenazine
      binding sites were heterogeneously distributed in the mesencephalon of control
      subjects: the density of tritiated dihydrotetrabenazine binding sites was high in
      the substantia nigra pars compacta, locus coeruleus and nucleus raphe dorsalis,
      moderate in the ventral tegmental area and low in the substantia nigra pars
      reticulata and catecholaminergic cell group A8. Within the substantia nigra, a
      zone with maximal density of tritiated dihydrotetrabenazine binding, two times
      higher than the mean estimate for the whole substantia nigra pars compacta, was
      detected in the medial part of the structure. The anatomical organization of the
      human ventral mesencephalon was analyzed on adjacent sections stained for
      acetylcholinesterase histochemistry and tyrosine hydroxylase
      immunohistochemistry. Tritiated dihydrotetrabenazine binding displayed the same
      characteristic regional pattern of distribution as that observed with tyrosine
      hydroxylase immunohistochemistry except in the nucleus raphe dorsalis, where no
      tyrosine hydroxylase immunoreactivity was detected. In parkinsonian brains, the
      level of tritiated dihydrotetrabenazine binding was dramatically decreased in all
      regions of the ventral mesencephalon analyzed except in the substantia nigra pars
      reticulata. In the substantia nigra pars compacta, the reduction was by 55% for
      the whole structure and by 65% in its medial zone, where binding site density was
      maximal. In most nigral subsectors analyzed, the decrease in density of tritiated
      dihydrotetrabenazine binding sites reached the level expected given the loss of
      tyrosine hydroxylase-positive cells observed. By contrast, the ratio of
      [3H]dihydrotetrabenazine binding to the number of tyrosine hydroxylase positive
      neurons was significantly increased in the zone of high [3H]dihydrotetrabenazine
      binding sites. This relative sparing of tritiated dihydrotetrabenazine binding
      sites may be due either to the contribution of other monoaminergic neurons such
      as serotoninergic neurons or more likely to hyperactivity of the still surviving
      dopaminergic neurons.

PMID- 8548310
TI  - Mechanisms of tumor necrosis factor-alpha (TNF-alpha) hyperalgesia.
AB  - Activation of immune cells by pathogens induces the release of a variety of
      proinflammatory cytokines, including IL-1 beta and TNF-alpha. Previous studies
      using IL-1 beta have demonstrated that this cytokine can alter brain function,
      resulting in a variety of 'illness responses' including increased sleep,
      decreased food intake, fever, etc. We have recently demonstrated that i.p. IL-1
      beta also produces hyperalgesia and that this hyperalgesia (as well as most
      illness responses) is mediated via activation of subdiaphragmatic vagal
      afferents. The present series of studies were designed to provide an initial
      examination of the generality of proinflammatory cytokine-induced hyperalgesia by
      examining the effects of i.p. TNF-alpha on pain responsivity. These studies
      demonstrate that: (a) i.p. TNF-alpha produces dose-dependent hyperalgesia as
      measured by the tailflick test, (b) this hyperalgesia is mediated via the induced
      release of IL-1 beta, (c) hyperalgesia is mediated via activation of
      subdiaphragmatic vagal afferents, and (d) the effects of subdiaphragmatic
      vagotomy cannot be explained by a generalized depression of neural excitability.

PMID- 8548311
TI  - Sleep effects following intrathecal administration of the 5-HT1A agonist 8-OH
      DPAT and the NMDA antagonist AP-5 in rats.
AB  - The modulating effect of an intrathecally (i.t.) administered 5-HT1A agonist and
      an NMDA antagonist on sleep, waking and EEG power spectra was investigated in
      rats. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38
      nmol) increased total slow wave sleep (TSWS) and decreased waking over the 8 h
      recording period. The TSWS increase was mostly due to an increase in SWS1. Sleep
      latency to SWS1 was also reduced. The NMDA antagonist dl-2-amino 5
      phosphonovaleric acid (AP-5) (31.5 nmol) reduced waking. SWS1 was increased, but
      TSWS was not changed. An increase in REM sleep was seen during the last part of
      the recording. Combined treatment with 8-OH-DPAT and AP-5 reduced waking and
      increased TSWS. No change in REM sleep was seen. There were no systematic changes
      in either waking, TSWS or REM fronto-frontal or fronto-parietal EEG power
      spectrum after any of the treatments. The results suggest that in the spinal cord
      stimulation of 5-HT1A receptors have a dampening effect on transmission of
      sensory information, leading to deactivation and thereby increased possibilities
      for sleep induction. Blockade of the NMDA receptors may also lead to a small
      dampening of sensory transmission with similar consequences.

PMID- 8548312
TI  - MK-801 reverses effects of chronic levodopa on D1 and D2 dopamine agonist-induced
      rotational behavior.
AB  - The effect of dizocilpine (MK-801) on dopaminergic agonist-induced rotational
      behavior was investigated in rats with 6-hydroxydopamine lesions of the
      nigrostriatal pathway after chronic administration of levodopa. The rotational
      response to the D2 agonist quinpirole was markedly increased in levodopa-treated
      animals compared with rats chronically administered saline. The increase in
      responsiveness to quinpirole was reversed by co-administered MK-801. Conversely,
      the rotational response to the D1 agonist SKF 38393 was reduced following chronic
      treatment with levodopa. The decrease in response to SKF 38393 was also reversed
      by MK-801. Chronic treatment with levodopa failed to alter the rotational
      responses to two other D1 preferring agonists SKF 81297 and SKF 82968, but
      responses to both agonists were increased by the co-administration of MK-801.
      These data support the hypothesis the MK-801 may reverse the differential changes
      in D1 and D2 agonist-induced motor responses which result from chronic treatment
      with levodopa.

PMID- 8548313
TI  - Intranigral GR-113808, a selective 5-HT4 receptor antagonist, attenuates morphine
      stimulated dopamine release in the rat striatum.
AB  - GR-113808, a potent and selective 5-HT4 receptor antagonist, was infused through
      a microdialysis probe into the striatum and nucleus accumbens of awake rats, and
      basal and morphine-stimulated extracellular concentrations of dopamine (DA) were
      measured in these regions. At 1 and 10 microM GR-113808 did not affect the
      extracellular concentrations of DA in either region and 100 microM significantly
      reduced dialysate DA only in the striatum. A subcutaneous dose of 5 mg/kg
      morphine significantly raised extracellular concentrations of DA in the striatum
      and nucleus accumbens from 60 to 120 min after injection and the effect was not
      modified by 10 microM GR-113808 infused through the probe 20 min before and for
      60 min after morphine. Bilateral injections of GR-113808 (1, 2.5 and 10
      micrograms/0.5 microliter) in the substantia nigra pars compacta did not affect
      dialysate DA in the striatum, except for a significant increase 120 min after the
      injection of 10 micrograms but the highest dose of GR-113808 prevented the
      increase of striatal DA caused by 5 mg/kg morphine s.c. The results suggest that
      5-HT4 receptors in the substantia nigra modulate the activity of the dopaminergic
      nigrostriatal system only when the neurons are activated.

PMID- 8548314
TI  - Brain dopamine transporter: gender differences and effect of chronic haloperidol.
AB  - Gender differences and the effect of chronic haloperidol on the rat brain
      dopamine transporter is reported. The density of striatal dopamine transporter
      sites labelled with [3H]GBR 12935, and of substantia nigra dopamine transporter
      mRNA measured by in situ hybridization were higher in female compared to male
      rats whereas striatal D2 specific binding labelled with [3H]spiperone was not
      significantly higher. Daily haloperidol treatment (1 mg/kg, i.p.) for 21 days
      increased striatal [3H]spiperone specific binding but left unchanged striatal
      [3H]GBR 12935 binding density and affinity as well as substantia nigra dopamine
      transporter mRNA levels. A reduce clearance rate of dopamine in the striatum
      after acute and chronic haloperidol was previously reported; the present results
      indicate that this may occur without changes in the sites of dopamine transport
      or in gene expression of this transporter.

PMID- 8548315
TI  - The anticonvulsant gabapentin enhances promoted release of GABA in hippocampus: a
      field potential analysis.
AB  - The mechanism of action of the recently developed anticonvulsant gabapentin (GBP)
      used for treatment of partial seizures [12] is largely unknown. Rat hippocampal
      slices were maintained in vitro and the effects of microapplication of nipecotic
      acid (NPA), which promotes the release and blocks uptake of GABA, on the
      synaptically-evoked population excitatory postsynaptic potential (EPSP) were
      assessed before and after 1 h bath application of GBP. GBP treatment did not
      alter the population EPSP amplitude to paired or multiple stimuli, but nearly
      doubled the shunting effects of NPA on the EPSP with no effect on the presynaptic
      volley. The NPA-induced shunting of the EPSP was bicuculline-sensitive,
      indicating its mediation by GABAA receptor activation. These results suggest that
      GBP may increase free GABA levels in hippocampal cells, the release of which may
      be enhanced under conditions of promoted GABA release. Moreover, the study
      presents a methodology to electrophysiologically assess relative free GABA levels
      using field potential analysis in the adult rat brain.

PMID- 8548316
TI  - Quantitative analysis of the olfactory pathway for drug delivery to the brain.
AB  - Following intranasal administration to rats, wheat germ agglutinin-horseradish
      peroxidase (WGA-HRP) concentrated in the olfactory nerve and glomerular layers of
      the olfactory bulb resulting in a mean olfactory bulb concentration of 140 nM. A
      negligible amount of label was detected in the olfactory bulb following
      intravenous administration of WGA-HRP or intranasal administration of
      unconjugated HRP. This is the first quantitative assessment of intraneuronal
      transport of a protein into the brain using the olfactory route.

PMID- 8548317
TI  - Development of regulation of melatonin release in pineal cells in chick embryo.
AB  - Melatonin release in a pineal cell culture from 13- and 14-day-old chick embryos
      increased during the dark phase and decreased during the light phase of a 12 h
      light:12 h dark cycle. When the light-dark cycle was reversed, the pattern of
      melatonin release in the culture also reversed. 8-Bromo cyclic-AMP stimulated
      melatonin release in both the light and dark phases. However, no rhythm of
      melatonin release was detected under constant dark (DD) conditions in a cell
      culture from 14-day-old chick embryos. In 18-day-old chick embryos, the pineal
      cell culture expressed a circadian rhythm of melatonin release under DD
      conditions. These results indicate that mechanisms regulating melatonin synthesis
      in the avian pineal gland are established during embryonic life.

PMID- 8548318
TI  - Survival of parvalbumin-immunoreactive neurons in the gerbil hippocampus
      following transient forebrain ischemia does not depend on HSP-70 protein
      induction.
AB  - HSP-70 was induced in the gerbil following 20 min of forebrain ischemia. The
      induction, as revealed with immunohistochemistry, is stronger and longer-lasting
      in CA3 and dentate gyrus than in CA1. Most neurons in this region, except
      GABAergic interneurons containing the calcium-binding protein parvalbumin,
      eventually cease to live as a result of delayed cell death. Double-labeling of
      inducible HSP-70 and parvalbumin has shown that no co-localization occurs in the
      hippocampus and neocortex of the gerbil in this model of transient forebrain
      ischemia. These results show that different thresholds of sensitivity and
      vulnerability exist for different subpopulations of neurons in the ischemic
      hippocampus, and suggest that HSP-70 protein induction is probably not essential
      for the survival of particular neuronal subpopulations subjected to transient
      ischemia.

PMID- 8548320
TI  - Taurine transport at the blood-brain barrier: an in vivo brain perfusion study.
AB  - Taurine transport into six brain regions of equithesin-anesthetized rats was
      studied by the in situ brain perfusion technique. This technique gives both
      accurate measurements of cerebrovascular amino acid transport and allows complete
      control of the perfusate amino acid composition. Final wash procedure showed that
      taurine efflux occurred rapidly from endothelial cells. The taurine influx into
      endothelial cells was sodium and chloride dependent suggesting that the sodium
      and chloride gradients are the principal source of energy for taurine transport
      into endothelial cells. Taurine transport could be fitted by a model with
      saturable components. The kinetic constants in the parietal cortex were 1.4 x 10(
      4) mumol/s/g for the apparent Vmax and 0.078 mM for the apparent Km. Competition
      experiments in the presence of sodium ions showed that [14C]taurine uptake was
      strongly inhibited by the structural analogs of taurine, hypotaurine and beta
      alanine.

PMID- 8548319
TI  - Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the
      accumbens, amygdala or striatum on cocaine self-administration in the rat.
AB  - This study tested the hypothesis that blockade of D-1 dopamine receptors in the
      nucleus accumbens shell, central nucleus of the amygdala or dorsal striatum by
      intracerebral microinjection of the dopamine antagonist SCH 23390 produces an
      attenuation of the effects of self-administered cocaine. Microinjection of SCH
      23390 (0-4.0 micrograms total dose) into any of the three brain regions dose
      dependently increased the rate of cocaine self-administration, consistent with a
      partial attenuation of the effects of cocaine under these conditions (0.25 mg
      cocaine i.v.; fixed-ratio 5 timeout 20 s). The regional rank order potency of SCH
      23390 was accumbens > amygdala > striatum, striatal injections being equipotent
      with subcutaneous administration. Moreover, SCH 23390 produced rapid effects on
      cocaine self-administration only when injected into the accumbens or amygdala.
      The time course of this regional selectivity was consistent with the rate of
      diffusion of SCH 23390 from the site of injection as measured by quantitative
      autoradiography, demonstrating that the regional selectivity of intracerebral
      injections of SCH 23390 is time-dependent. These results support a role for D-1
      dopamine receptors in the nucleus accumbens and amygdala in the effects of self
      administered cocaine, and suggest that D-1 receptors in certain portions of the
      'extended amygdala' may be an important substrate for the reinforcing actions of
      cocaine.

PMID- 8548321
TI  - Dopamine release in the medial preoptic area during male copulatory behavior in
      rats.
AB  - In vivo microdialysis was employed to measure the extracellular concentrations of
      dopamine (DA) in the medial preoptic area (MPOA) of rats during male sexual
      activity to look for a correlation with sexual activity. During copulation, the
      concentration of DA in the MPOA was significantly increased. A significant
      difference was detected in changes of DA between copulators and non-copulators.
      These findings were consistent with the assertion that DA neuron activity in the
      MPOA facilities male copulatory behavior.

PMID- 8548322
TI  - Dexamethasone down-regulates the expression of endothelin B receptor mRNA in the
      rat brain.
AB  - The present study was designed to examine effects of dexamethasone on the steady
      state level of endothelin B(ETB) receptor mRNA in in vivo the rat brain. ETB
      receptor mRNA was very high at the hypothalamus and cerebellum but was
      comparatively low at the striatum and amygdala. Dexamethasone, 1 and 7 mg/kg,
      i.p., markedly and dose-relatedly decreased ETB receptor mRNA level with slow
      onset of 8hr at the hypothalamus and cerebellum, but did not induced a marked
      decrease at other areas. On the contrary, dexamethasone produced an increase of
      ET-1 mRNA which preceded to the decrease of ETB receptor mRNA at the same brain
      areas. Phosphoramidon, a endothelin-converting enzyme inhibitor, did not
      antagonized but potentiated the effect of dexamethasone. Besides, phosphoramidon
      per se markedly stimulated the expression of ET-1 mRNA. The results suggested
      that dexamethasone down-regulates ETB receptor mRNA level at the hypothalamus and
      cerebellum of rat brain and these effects may be involved in the increase of ET-1
      peptide gene transcription.

PMID- 8548323
TI  - Stimulation of A1 adenosine receptors mimics the electroencephalographic effects
      of sleep deprivation.
AB  - N6-Cyclopentyladenosine (CPA), an A1 adenosine receptor agonist, increased EEG
      slow-wave activity in nonREM sleep when administered either systemically (0.1-3
      mg/kg) or intracerebroventricularly (3.5-10 micrograms) in the rat. The power
      spectrum of EEG changes (as calculated by Fourier analysis) matched that produced
      by total sleep deprivation in the rat. The effects of CPA on the nonREM-sleep EEG
      were dose-dependent. These findings suggest that adenosine is an endogenous
      mediator of sleep-deprivation induced increases in EEG slow-wave activity, and
      therefore that increased adenosine release is a concomitant of accumulation of
      sleep need and may be involved in homeostatic feedback control of sleep
      expression.

PMID- 8548324
TI  - Apamin, a selective SK potassium channel blocker, suppresses REM sleep without a
      compensatory rebound.
AB  - To determine the role of neuronal potassium conductance in rapid-eye-movement
      (REM)-sleep homeostasis, we have administered small doses of apamin (2-5 ng), a
      selective blocker of the calcium-dependent SK potassium channel, injected into
      the lateral ventricle in rats, and characterized the resultant effects on REM
      sleep expression. Apamin produces a dose-dependent reduction in REM-sleep
      expression without an increase in the frequency of attempts to enter REM sleep,
      suggesting that accumulation of REM-sleep propensity is suppressed. The vast
      majority (84-95%) of lost REM sleep is not recovered 40 h after apamin
      administration. These findings suggest that accumulation of REM-sleep propensity
      is linked to the increased neuronal potassium conductance in nonREM sleep.

PMID- 8548325
TI  - The effect of MK-801 and SCH23390 on the expression and sensitization of morphine
      induced oral stereotypy.
AB  - Repeated high doses of morphine sulfate, administered in a 24-36 h period,
      stimulates the expression of oral stereotypy in rats. Sensitization to this
      effect of morphine is demonstrated by the reexpression of the stereotypy by the
      administration of 4.0 mg/kg of morphine one week following the original exposure.
      To investigate the role of N-methyl-D-aspartic acid (NMDA) and D1 dopamine (DA)
      receptors in the acute expression and sensitization of morphine-induced oral
      stereotypy, rats were administered four injections of morphine (10.0 mg/kg) one
      injection every 12 h and observed for the expression of stereotypic behaviors
      following pretreatment with selective antagonists. Pretreatment with the NMDA
      antagonist, MK-801 (0.7 mg/kg), before each of the four morphine injections
      antagonized both the initial expression of oral stereotypy and the development of
      sensitization. In contrast, the DA D1 receptor antagonist SCH23390 (40.0
      micrograms/kg) administered during the four high-dose treatments with morphine
      antagonized the initial expression of oral stereotypy and not the development of
      sensitization. These findings implicate glutamate's action at the NMDA receptor
      in both the acute expression of morphine-induced oral stereotypy, and the
      development of sensitization of this morphine effect, whereas DA D1 receptors may
      only be involved in the acute expression of the stereotypy.

PMID- 8548326
TI  - Substance P- and GABA-like immunoreactivities are co-localized in axonal
      varicosities in the superficial laminae of cat but not rat spinal cord.
AB  - In the present study, we applied a combination of pre-embedding peroxidase-based
      immunocytochemistry and post-embedding immunogold staining to examine the
      synaptic interactions of substance P (SP) and gamma-aminobutyric acid (GABA) in
      the superficial laminae of the dorsal horn of cat and rat spinal cord. We
      demonstrate for the first time the co-existence of SP and GABA immunoreactivities
      in axonal boutons in laminae I-III of cat spinal dorsal horn. In cat, most SP +
      GABA immunoreactive (IR) axonal boutons established synapses with SP-IR or non-IR
      dendrites. These synapses were exclusively symmetric. Quantitative analysis
      showed that the percentage of SP/GABA double labelled bouton profiles was higher
      (7%) in lamina I but was considerably lower in laminae IIo, IIi and III.
      Similarly, the density (number of bouton profiles per 100 microns2) of SP + GABA
      IR bouton profiles was highest in lamina I. However, in agreement with previous
      studies, the co-localization of SP and GABA immunoreactivities was never detected
      in the rat dorsal horn. In both species, SP + GABA-IR or GABA-IR axonal bouton
      profiles were never seen presynaptic to SP-IR boutons. These findings provide a
      morphological basis for the interaction of excitatory and inhibitory agents in
      the nociceptive circuits in the dorsal horn of the cat and rat spinal cord.

PMID- 8548327
TI  - HIV gp120-specific cell-mediated immune responses in mice after oral immunization
      with recombinant Salmonella.
AB  - Salmonella is of great interest as a potential human immunodeficiency virus
      vaccine vector because of its ability to elicit potent mucosal and systemic
      immune responses when administered orally. To determine whether such a vaccine
      could elicit an immune response in mice, plasmids expressing HIV gp120-LAI were
      introduced into attenuated S. typhimurium. Three serial doses of 10(10)
      recombinant organisms were administered orally to BALB/c mice at 2-week
      intervals. Immunized mice but not control mice demonstrated proliferative T cell
      responses to gp120-LAI, comparable in magnitude to the proliferative responses to
      Salmonella antigens. Immunized mice had detectable serum and intestinal
      Salmonella-specific IgA and serum Salmonella-specific IgG. However, no gp120
      specific antibody was detected in either serum or intestinal washes. These
      results indicate that live recombinant Salmonella-based vaccine constructs can
      induce HIV-specific cellular immune responses in vivo.

PMID- 8548328
TI  - Inhibition of HIV-1-induced syncytia formation and infectivity by
      lipophosphoglycan from Leishmania.
AB  - In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is
      associated with a more rapid decline of CD4+ cells and progression to AIDS.
      Agents that inhibit either virus infection or syncytia formation have the
      potential to be therapeutically useful. Lipophosphoglycan (LPG), the major
      glycoconjugate of Leishmania, was recently shown to be a potent nonspecific
      inhibitor of viral membrane fusion. In this study, LPG demonstrated a dose
      dependent inhibition of HIV-1-induced syncytia formation in CD4+ MT-2 cells
      infected with distinct SI isolates. Fragments of LPG were used to show that
      inhibition of syncytia formation was dependent on the length of the LPG fragment.
      Treatment of CD4+ cells or HIV-1 isolates with LPG inhibited infection in vitro.
      Furthermore, LPG inhibited the replication of SI viral isolates in CD4+ T cells
      in vitro. LPG had no toxic effects on peripheral blood mononuclear cells at the
      highest concentrations used in these assays. Further, LPG rapidly associated with
      the surface membrane of a human T cell line and subsequently disassociated over a
      24-h period. The development of compounds capable of inhibiting HIV-induced
      syncytia formation should provide novel therapeutic approaches to control the
      spread of virus and disease progression.

PMID- 8548329
TI  - Amino acid sequence requirements for the incorporation of the Vpx protein of
      simian immunodeficiency virus into virion particles.
AB  - To investigate the amino acid sequence determinants for the incorporation of Vpx
      protein into virion particles, several mutations were introduced into the vpx
      gene of SIVmac239 proviral DNA, and the effects of mutations on the expression
      and assembly of the Vpx protein were studied. The results show that deletions of
      amino acids from 78 to 80 or from 82 to 87 abolished the incorporation of the
      expressed Vpx protein into virion particles. Other Vpx mutants, including a full
      length Vpx-Vpr fusion protein and a mutant with a deletion of the C-terminal
      polyproline tract, were packaged efficiently. This study suggests that amino
      acids from 78 to 80 and 82 to 87 are important for the assembly of the Vpx
      protein into virus particles.

PMID- 8548330
TI  - Increased expression of tumor necrosis factor-alpha receptors in the brains of
      patients with AIDS.
AB  - Tumor necrosis factor (TNF)-alpha has been shown to be increased in brain tissue
      of AIDS patients and may function as a mediator of cerebral damage. We initiated
      a study to determine the cellular localization and degree of protein and mRNA
      expression of the two specific TNF-alpha receptors (TNF-Rs), p55 and p75, in
      brain tissues from AIDS patients. Cerebral white matter obtained at autopsy from
      13 AIDS patients, 10 unhealthy controls, and 4 healthy controls was evaluated.
      Double-label immunohistochemistry revealed prominent up-regulation of p55 and p75
      TNF-Rs on activated macrophages and microglial cells in all AIDS patients; no
      increased staining was found on astrocytes. Staining was most prominent in
      patients with opportunistic infection of the brain and in microglial nodules of
      patients with HIV encephalitis. Brain tissues also showed increased expression of
      interleukin (IL)-1 beta, IL-6, and TNF-alpha, cytokines known to up-regulate the
      TNF-Rs. Increased staining for TNF-Rs was also found in patients with multiple
      sclerosis, chronic cerebral edema, and radiation necrosis but not in an
      asymptomatic HIV-positive patient without AIDS. Reverse transcriptase polymerase
      chain reaction performed on adjacent sections from five AIDS patients revealed up
      regulation from normal for p55 in all patients and for p75 in three patients. The
      up-regulation of both TNF-Rs in AIDS suggests that macrophages and microglial
      cells may be important in amplifying the TNF-alpha response.

PMID- 8548331
TI  - Evaluation of four alternative methodologies for determination of absolute CD4+
      lymphocyte counts. The National Heart, Lung, and Blood Institute Retrovirus
      Epidemiology Donor Study.
AB  - Standard methods for determining absolute CD3+CD4+ T-lymphocyte concentrations
      using combined results from flow cytometry and hematology analyzers are expensive
      and require fresh (< 18 h old) blood. We evaluated four new "alternative" methods
      for determining absolute CD4+ T-lymphocyte counts; (a) the FACSCount System
      (Becton Dickinson Immunocytometry Systems), (b) VCS Technology/Coulter Cyto
      Spheres (Coulter Corporation), (c) Zymmune CD4/CD8 Cell Monitoring Kit (Zynaxis,
      Inc.), and (d) TRAx CD4 Test Kit (T Cell Diagnostics). EDTA-anticoagulated whole
      blood specimens from HIV-seropositive patients and anti-HIV-negative adult blood
      donors and staff were tested by the standard flow cytometry method on fresh blood
      (0-6 postphlebotomy) and by the four alternative methods at 0 to 6 h and 24 to 30
      h postphlebotomy. Representative specimens (< 6 h old) were tested five times
      with each system to evaluate reproducibility. Correlation coefficients for
      absolute CD4+ counts between standard flow cytometry and the alternative methods
      ranged from 0.84 to 0.92 for both fresh and 24- to 30-h-old specimens. Average
      coefficient of variation for reproducibility ranged from 4.5 to 7.1%. The four
      alternative CD4+ T-lymphocyte counting methods performed well relative to
      standard methods. Each alternative method offers advantages over standard flow
      cytometry with respect to sample throughout, required technical expertise, and
      cost per result. These methods should facilitate wider availability of low-cost
      CD4 counts.

PMID- 8548332
TI  - Soluble tumor necrosis factor receptors as surrogate markers for the assessment
      of zidovudine treatment in asymptomatic HIV-1 infection.
AB  - In untreated, asymptomatic human immunodeficiency virus type 1 (HIV-1) infection,
      elevated serum concentrations of soluble receptors for tumor necrosis factor
      (sTNFR) types I and II are associated with progression to AIDS. To assess the
      utility of sTNFRs as markers for the assessment of antiretroviral treatment,
      sTNFRs were sequentially determined in 47 asymptomatic HIV-1-infected men, who
      participated in a double-blind, randomized, placebo-controlled study. Progression
      to AIDS or severe AIDS-related complex occurred in six zidovudine (ZDV)- and six
      placebo-treated subjects. During ZDV treatment (n = 28) both types of sTNFRs
      declined compared with baseline and placebo, whereas they increased during
      placebo treatment (n = 19). A sustained decline of sTNFRs occurred only in
      subjects who experienced no disease progression. During the first 3 months of ZDV
      treatment, the hazard ratio for disease progression when sTNFR type II rose above
      the baseline value plus 5% was significantly increased (hazard ratio:
      approximately 25; 95% confidence interval: approximately 1.5-400; p < 0.03).
      Simultaneously determined CD4+ counts and serum neopterin levels showed a similar
      pattern in progressors and nonprogressors. Thus, in contrast to CD4+ counts and
      neopterin levels, sTNFR concentrations, especially those of the type II STNFR,
      appear to be valuable surrogate markers for monitoring the efficacy of ZDV
      treatment in asymptomatic HIV-1 infection.

PMID- 8548333
TI  - Abnormalities of measles antibody response in human immunodeficiency virus type 1
      (HIV-1) infection.
AB  - The finding that severe measles occurs in immunized as well as nonimmunized human
      immunodeficiency virus (HIV)-infected individuals suggests that both immunologic
      memory and the initial response to measles may be impaired by HIV infection. That
      the initial response is affected was supported by the finding that post-measles
      immunization titers of HIV-infected babies were significantly lower (p = 0.01)
      than those of normal babies. Poor immunologic memory was evidenced in HIV
      infected children by lower titers than in normal children (p < 0.001) and by a
      continuing decline in measles antibody that was not arrested by reimmunization.
      Impaired memory appeared to be associated with defective avidity maturation. HIV
      infected babies and infants or children had a significantly lower avidity index
      (AI) than age-matched normal children (p < 0.01). HIV-infected adults, who were
      infected with HIV following infection with measles, did not have AI values
      significantly different from normal adults (p = 0.18) but had significantly
      greater values than did HIV-infected babies and children (p < 0.01). Thus, in
      contrast to infants and children who were infected with HIV before measles
      immunization, the adult immune response to measles was less affected.

PMID- 8548334
TI  - The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients
      with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of
      the National Institute of Allergy and Infectious Diseases.
AB  - Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial
      of N-butyl-deoxynojirimycin, an alpha-glucosidase I inhibitor that inhibits human
      immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120.
      Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64
      mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual
      and because the study was stopped after the finding of cataracts in initial long
      range rat toxicology studies. These cataracts were later shown to be transient
      and not found in other animals. The most common side effects were
      gastrointestinal, with diarrhea and flatulence occurring in most subjects, which
      seemed to partially improve on a modified diet that excluded complex
      carbohydrates. Grade III elevations in liver function tests were seen in two
      patients. Grade III leukopenia and neutropenia were seen in seven patients, but
      were only severe enough in two to require discontinuation. No significant trends
      in CD4 cell counts or HIV-1 p24 levels were noted.

PMID- 8548335
TI  - Alcohol, sexual practices, and risk of AIDS among blacks, Hispanics, and whites.
AB  - The association of alcohol consumption and unsafe sexual behavior known to
      increase the risk of HIV transmission was examined among blacks, Hispanics, and
      whites. Data were obtained from a 1990 general population survey on alcohol use
      that included questions on sexual behavior. Analyses examined sex and ethnic
      differences in patterns of sexual behavior and the influence of demographic
      factors and alcohol use on risky sexual behavior. Patterns of sexual behavior
      differed by ethnicity and sex, with black and Hispanic men reporting more
      frequent sexual intercourse and a greater number of sexual partners. Women who
      were single and heavier drinkers with a longer history of sexual activity and of
      Hispanic origin were more likely to engage in risky sexual behavior. Men who were
      younger, single, heavier drinkers, and less religious were more likely to engage
      in unsafe sex, with black men being most at risk. The association of alcohol with
      unsafe sexual behavior implies that combining AIDS education with interventions
      that aim at reducing levels of alcohol use might lead to more effective AIDS
      prevention programs among high-risk populations.

PMID- 8548336
TI  - Differences in participation in experimental drug trials among persons with AIDS.
AB  - To measure participation in experimental drug trials among persons with acquired
      immunodeficiency syndrome (AIDS), we interviewed 4,604 persons at least 18 years
      of age who were reported to have AIDS to 11 state and city health departments in
      the United States. Ten percent reported that they were currently in a trial.
      Current enrollment differed significantly (p < 0.05) by race/ethnicity (blacks,
      5%; whites, 14%; Hispanics, 15%), gender (women, 7%; men, 11%), exposure mode
      (injection drug use, 5%, men who have sex with men, 14%), annual household income
      (< $10,000, 8%, > or = $10,000, 14%), education (< 12 years, 6%; > or = 12 years,
      12%), health care (no regular care, 1%, public care, 8%; private care, 17%), and
      time since AIDS diagnosis (< or = 6 months, 9%; > 6 months, 12%). Adjusting for
      all factors and time since AIDS diagnosis, blacks (adjusted odds ratio [AOR] =
      0.35, 95% confidence interval [CI] 0.26, 0.47), persons with less than 12 years
      of education (AOR = 0.71, CI 0.53, 0.96), and those without regular health care
      (AOR = 0.24, CI 0.10, 0.61) remained less likely to be in a trial. Blacks, those
      with less than 12 years of education, and persons without regular health care
      were less likely than other persons with AIDS to be currently enrolled in AIDS
      trials. To increase enrollment of these persons, researchers must address
      barriers to participation for these groups.

PMID- 8548337
TI  - AIDS knowledge, risk behaviors, and condom use among four groups of female sex
      workers in Bali, Indonesia.
AB  - The objectives of this study were to discover the AIDS knowledge, risk behaviors,
      and condom use of four groups of female professional sex workers (n = 614).
      Personal interviews were conducted with women working in low-price brothels, mid
      price and high-price houses, and tourist areas. Only 51% of women in the low
      price brothels had heard of AIDs, although most of the women in the other groups
      had heard of it. Knowledge of transmission and symptoms was weak in all groups,
      and most women were unaware of asymptomatic transmission. Most women felt safe
      from HIV due to ineffective strategies such as taking medications or client
      selection practices. Condom use with clients varied widely by group. Women in the
      low-price brothels reported the lowest levels of use (19% of encounters in the
      previous week), with women from the mid- and high-price groups reporting higher
      levels (68% mid-price; 71% high-price). Women working in the tourist areas
      reported the highest levels of use (90%). Interventions for each group need to
      reflect these differences in knowledge as well as the contexts of their work;
      important contextual factors to consider include the level of AIDS and STD
      knowledge in their environment, the characteristics of the clients served, and
      the degree of supervision that they receive.

PMID- 8548338
TI  - Will preventive HIV vaccine efficacy trials be possible with female injection
      drug users?
AB  - This article examines whether preventive HIV vaccines trials will be viable among
      female injection drug users (IDUs). Of the 137 women who completed baseline
      serologic and behavioral assessments, 121 (88%) were seronegative; all enrolled
      in Project Jumpstart in Philadelphia (PA, U.S.A.), a vaccine preparedness
      initiative cosponsored by NIAID and NIDA. Subjects were seen every 3 months for
      risk and vaccine opinion assessment, risk reduction counseling, and HIV antibody
      testing. The baseline prevalence rate of HIV infection was 12% (16 of 137) with
      an annual incidence rate of 3.5% (4 of 114) during the first year. Of the 121
      baseline seronegative women, 28% shared needles and 52% engaged in unprotected
      intercourse. Sixty percent of the baseline seronegative women reported being
      willing to be one of the first people to try an HIV vaccine. According to
      logistic regression, needle sharers were 12.8 times more likely, women who
      engaged in sex for drugs or money 6.6 times more likely, out-of-treatment women
      3.5 times more likely, and those who believed that vaccines can prevent disease
      acquisition 3 times more likely to report willingness to try an HIV vaccine than
      their respective counterparts. At 1-year postbaseline assessment, 98% of the
      women had behavioral data collected and 95% had serologic specimens collected.
      Given that seroconversions occur and that these women engage in risk behaviors,
      report willingness to try an HIV vaccine, and can be retained for longitudinal
      assessment, they appear to be suitable participants for preventive HIV vaccine
      efficacy trials. Nonetheless, work is required to insure that these women make
      informed and knowledgeable decisions regarding trial enrollment.

PMID- 8548339
TI  - Development of zidovudine (AZT) resistance in Jurkat T cells is associated with
      decreased expression of the thymidine kinase (TK) gene and hypermethylation of
      the 5' end of human TK gene.
AB  - The T-cell line Jurkat E6-1 was rendered resistant to zidovudine (AZT) in vitro
      by exposure to low but gradually increased concentrations of the drug.
      Biochemical pharmacology studies of [3H]AZT in the AZT-resistant T-cell lines
      showed a significant reduction of AZT phosphorylation to the mono-, di-, and
      triphosphate anabolites. Peripheral blood mononuclear cells (PBMCs) from
      pediatric patients with human immunodeficiency virus type 1 (HIV-1) infection
      showed a similar pattern of decreased AZT anabolism. Enzymatic studies with
      purified thymidine kinase (TK) preparations from these cell lines showed a
      gradual decline in Vmax related to their level of resistance to AZT. The
      Jurkat/AZT-20 and Jurkat/AZT-100 cells were studied in greater detail with
      reverse transcriptase/polymerase chain reaction (RT/PCR) cloned probes to
      determine possible molecular mechanisms of resistance to AZT. TK mRNA was
      significantly decreased (approximately 5- to 10-fold) in the AZT-resistant T-cell
      lines. Southern blot analyses indicated that there were no major rearrangements
      or deletions of the TK gene, but the 5' end of the gene in the AZT-resistant
      cells is highly methylated when compared to wild-type cells. No apparent
      differences were seen in thymidylate kinase (dTMPk) mRNA levels in the same T
      cell lines. Thus the decreased expression of TK mRNA and resultant TK enzymatic
      activity is responsible for the observed reduction in the AZT anabolism in the
      resistant T-cell lines. Decreased T-cell TK activity could allow wild-type, AZT
      sensitive HIV-1 to replicate in the presence of subinhibitory AZT triphosphate
      (AZT-TP) cellular concentrations enabling a genetic variant with drug resistance
      to emerge and outgrow the AZT-sensitive, wild-type virus.

PMID- 8548340
TI  - Functional analysis of the phosphorylation sites on the human immunodeficiency
      virus type 1 Vpu protein.
AB  - The human immunodeficiency virus type 1 (HIV-1)-encoded vpu product is a small
      class 1 integral membrane protein that is phosphorylated by the ubiquitous casein
      kinase II (CKII) in HIV-1-infected cells. The Vpu protein facilitates the release
      of budding virions from the surface of infected cells and delays the rate of
      syncytium formation. In this study, we investigated the role of phosphorylation
      in the biological activity of Vpu. Our results show that phosphorylation of Vpu
      occurs on serine residues at positions 52 and 56 located in a highly conserved
      dodecapeptide sequence. Mutation of either Ser 56, or both Ser 52 and Ser 56
      impaired the ability of Vpu to delay the rate of syncytium formation while
      retaining virion release activity at levels comparable to vpu+ proviruses. Flow
      cytometry analysis indicates that the relative amounts of envelope glycoprotein
      gp120 expressed at the surface of cells transfected with these vpu mutant
      proviruses was two- to threefold greater than that observed on cells transfected
      with a vpu+ provirus. This increased expression of gp120 at the cell surface may
      explain the more rapid onset of syncytium formation observed in cell transfected
      with vpu mutant proviruses. These results suggest that Vpu-facilitated virion
      release and delayed cytopathic effect are the consequence of two distinct
      functional activities of the protein.

PMID- 8548341
TI  - Hypercalcemia associated with cytomegalovirus infection in an AIDS patient.

PMID- 8548342
TI  - Review of invasive cervical cancer cases for AIDS surveillance.

PMID- 8548344
TI  - Markers and determinants of disease progression in children with HIV infection.
      The Pediatric AIDS Siena Workshop II.

PMID- 8548343
TI  - Neurologic manifestations of AIDS: a comparative study of two populations from
      Mexico and the United States.
AB  - Neurologic complications associated with human immunodeficiency virus type 1 (HIV
      1) infection vary geographically. To understand the pattern of HIV-associated
      neurologic complications in Mexico, 120 AIDS patients from Mexico City, Mexico,
      and 500 AIDS patients from Houston, Texas, were studied cross-sectionally and
      retrospectively. Neurologic, laboratory, imaging, and pathologic examinations
      identified 40 Mexican patients and 130 U.S. patients with neurologic
      complications. Whereas AIDS dementia complex was the most common neurologic
      manifestation in both groups, intracranial tuberculoma was present only in the
      Mexican population (10%). Primary brain lymphoma was more prevalent in the U.S.
      population (8.4%). The different findings in the Mexican population likely
      reflect afflictions common to developing countries--a high prevalence of
      tuberculosis and a high mortality rate. These conditions preclude complications
      such as lymphoma, which develop later in the natural course of HIV infection.

PMID- 8548345
TI  - Continuous low-dose interferon-alpha therapy for HIV-related immune
      thrombocytopenic purpura.
AB  - Our objective was to examine the efficacy and toxicity of continuous, low-dose
      interferon-alpha therapy for human immunodeficiency virus-related immune
      thrombocytopenic purpura (HIV-ITP) in a Phase II clinical trial overseen by a
      community-based consortium of physicians conducting clinical trials in HIV
      related diseases. Sixteen patients with HIV-ITP defined by prospective clinical
      criteria were enrolled; the majority had failed other therapies for HIV-ITP.
      Baseline and serial measurements were made of platelet counts, complete blood
      counts, serum chemistries, platelet-associated immunoglobulin, and CD4+ T
      lymphocyte counts; subjective symptoms and bleeding were recorded. Three million
      units of interferon-alpha 2b were self-administered by subcutaneous injection
      every Monday, Wednesday, and Friday for 16 weeks. Thirteen participants were
      evaluable for response. One obtained a complete response, eight had partial
      responses, and four had no response to interferon-alpha therapy. The mean
      absolute platelet count of the group rose from 15.5 x 10(9)/L at baseline to 47.3
      x 10(9)/L at 2 weeks and remained in this range for the duration of the study.
      CD4+ T-lymphocyte counts and serum chemistries did not change significantly
      during therapy. Ability to detect platelet-associated immunoglobulin did not
      change in a predictable manner in relation to platelet count response.
      Hematologic toxicity was limited to one episode of granulocytopenia, which
      resolved after a lowering of zidovudine dosage. Subjective toxicities were mild
      and tolerable, and minor bleeding problems improved in all participants so
      affected. Low-dose, continuous therapy with interferon-alpha resulted in
      meaningful increases in the platelet counts of the majority of study participants
      with HIV-ITP. Interferon-alpha was safe and tolerable for most participants with
      HIV-ITP at the dosage and schedule employed in this study. Interferon-alpha for
      clinically significant thrombocytopenia and who have failed to respond to
      zidovudine.

PMID- 8548346
TI  - Bacteremia in hospitalized patients infected with the human immunodeficiency
      virus: a case-control study of risk factors and outcome.
AB  - We reviewed all episodes of nonmycobacterial bacteremias in human
      immunodeficiency virus (HIV)-infected patients from 1990 to 1991 to determine the
      incidence, risk factors, and outcome. Forty-five patients had a total of 63
      episodes of bacteremia (9% of 689 HIV-related hospitalizations). In this cohort,
      the median CD4+ lymphocyte count was 17 cells/mm3, 71% had AIDS, and 78% were
      homosexual men. The most frequently isolated bacteria were Staphylococcus aureus
      (25%) and coagulase-negative staphylococci (22%). The most common site of
      infection was intravenous catheter-related, accounting for 35% of the
      bacteremias. Compared to HIV-infected, nonbacteremic controls, patients with
      bacteremia detected at admission were more likely to have an indwelling
      intravenous catheter (p = 0.003) and less likely to be likely zidovudine (p =
      0.04). The overall in-hospital mortality rate was 24%. There was no significant
      difference in the in-hospital mortality rates in bacteremic patients with or
      without HIV infection. Seventeen patients had more than one episode of bacteremia
      (71% had recurrence with the same organism). We conclude that bacteremia is a
      significant problem in HIV-infected persons with low CD4+ lymphocyte counts,
      often related to the presence of an intravenous catheter; recurrence is common.
      In addition, HIV infection does not appear to increase the mortality rate for
      bacteremia.

PMID- 8548347
TI  - Health insurance and use of medical services by men infected with HIV.
AB  - Among 178 HIV-infected men from the San Francisco City Clinic Cohort (SFCCC), we
      examined the association between health insurance and use of outpatient services
      and treatment. For men with private insurance, we also assessed the frequency of
      avoiding the use of health insurance. Men without private insurance reported
      fewer outpatient visits than men with fee-for-service or managed-care plans. Use
      of zidovudine for eligible men was similar for those with fee-for-service plans
      (74%), managed-care plans (77%), or no insurance (61%). Use of Pneumocytstis
      carinii pneumonia prophylaxis was similar for those with fee-for-service (93%)
      and managed-care plans (83%) but lower for those with no insurance (63%). Of 149
      men with private insurance, 31 (21%) reported that they had avoided using their
      health insurance for medical expenses in the previous year. In multivariate
      analysis, the independent predictors of avoiding the use of insurance were
      working for a small company and living outside the San Francisco Bay Area. Having
      private insurance resulted in higher use of outpatient services, but the type of
      private insurance did not appear to affect the use of service or treatment. Fears
      of loss of coverage and confidentiality may negate some benefits of health
      insurance for HIV-infected persons.

PMID- 8548348
TI  - Removal of human immunodeficiency virus by an 0.04-micron membrane filter.
AB  - We tested the ability of a 0.04-micron nylon membrane filter to remove human
      immunodeficiency virus (HIV) from tissue culture media containing 10% fetal calf
      serum. Endpoint titrations of infectious virus (ID50) were performed on
      lymphocyte cultures. The presence of virus in the cultures was determined using
      an enzyme-linked immunoabsorbant assay (ELISA) of the HIV-1 P24 core antigen. In
      repeated experiments, filtration of the virus suspension resulted in the removal
      of HIV below detectable limits. The titer reduction was estimated to be greater
      than 8.5 x 10(2). These results suggest that this filter is effective in removing
      HIV from fluids containing serum or serum products.

PMID- 8548349
TI  - Changes in markers of disease progression in HIV-1 seroconverters: a comparison
      between cohorts of injecting drug users and homosexual men.
AB  - Comparisons of human immunodeficiency virus (HIV) disease progression between
      risk groups are difficult primarily because of the long incubation period of
      acquired immune deficiency syndrome (AIDS) and unknown times of infection. This
      is believed to be the first study that directly compared changes in T-lymphocyte
      subsets following HIV-1 seroconversion between cohorts of predominantly black
      injecting drug users and predominantly white homosexual men. Longitudinal trends
      of CD4 and CD8 percentages of total lymphocytes during 4 years were modeled as
      piecewise linear functions with a two-parameter correlation structure to
      accommodate within-person repeated observations. Prior to seroconversion the 151
      injecting drug users started with similar CD4% and CD8% levels compared with the
      99 homosexual men. Following seroconversion, larger changes were observed overall
      in the homosexual men compared with the injecting drug users for both markers (p
      < or = 0.001). The major discrepancies, however, were limited to the first 2
      years. Subsequently, the CD4% levels of the two cohorts converged and then
      declined at similar rates. These comparative analyses of HIV seroconverters in
      homosexual men and injecting drug users suggest that risk group has only a minor
      effect on the initial course of HIV infection.

PMID- 8548350
TI  - Incidence proportion of and risk factors for AIDS patients diagnosed with HIV
      dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.
AB  - We undertook this study to determine the incidence proportion of and risk factors
      for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia,
      central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A
      historical cohort of 487 consecutive inpatients with AIDS treated by San
      Francisco General Hospital inpatient and outpatient services entered the study.
      We abstracted all available records for demographic information, diagnoses, and
      dates of death and estimated the incidence proportion of AIDS patients diagnosed
      with major CNS complications using the Kaplan-Meier method. We used the Cox
      proportional hazards model to analyze the effect of demographic factors on the
      hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated
      incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years
      of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were
      0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal
      meningitis. Only HIV dementia was independently associated with increasing age at
      AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence
      interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41
      15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19
      3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about
      equally common complications in patients with AIDS, but only HIV dementia is
      associated with increasing age at AIDS diagnosis and injection drug use.

PMID- 8548351
TI  - Male circumcision, sexually transmitted disease, and risk of HIV.
AB  - Our objective was to describe associations among male circumcision, behavioral
      and demographic variables, ulcerative and nonulcerative sexually transmitted
      disease (STD), and human immunodeficiency virus (HIV) infection via a cross
      sectional study in Kigali, the capital of Rwanda. Our subjects were 837 married
      men who volunteered for HIV testing and counselling. Uncircumcised men had a
      relatively low-risk profile in that they reported fewer lifetime sexual partners
      and prostitute contacts than circumcised men and were more likely to live in
      rural areas with lower HIV prevalence rates. Uncircumcised men were also less
      likely to report a history of sexually transmitted disease (64% versus 73%, p =
      0.01), although they were more likely to report genital ulceration (GUD) (24%
      versus 17%, p < 0.03) and to have inguinal adenopathy noted on physical exam (42%
      versus 29%, p = 0.009). Despite the low-risk profile, uncircumcised men had a
      higher prevalence of HIV infection than circumcised men (29% versus 21% HIV
      positive, p = 0.02), which was most marked in men reporting five or more lifetime
      sex partners (36% versus 23% HIV positive, p = 0.005) or contact with prostitutes
      (35% versus 23% HIV positive, p = 0.009). Circumcision remained a predictor of
      HIV infection in multivariate analyses (multivariate odds ratio 1.69, 95%
      confidence interval 1.16-2.47). Lack of circumcision is associated with a higher
      risk of HIV infection in Rwandan men. Further research is needed to determine
      whether this higher risk is due in part to poor hygiene or to complex mechanisms
      operating through the acquisition of other sexually transmitted diseases.
      Circumcision may be an appropriate risk reduction approach for men with known
      exposures to the virus when there are constraints to alternatives, such as condom
      use.

PMID- 8548352
TI  - HIV/HTLV-I coinfection and clinical grade at diagnosis.
AB  - A total of 963 HIV-infected patients have been identified or followed up in
      Martinique since 1985. Medical files were used to retrieve information about age,
      sex, circumstances of diagnosis, HTLV-I status, and HIV clinical grade at first
      examination according to CDC criteria from 1987. Complete information was
      available for 774 patients. At the first clinical examination, the clinical grade
      of 65 coinfected patients was more severe than that of the monoinfected patients
      (GIV versus GII, OR = 2.60, p < 0.01), but after adjustment for age and sex, this
      odds ratio was reduced 1.57. Although this study cannot invalidate the hypothesis
      of a faster progression toward AIDS of coinfected than of monoinfected patients,
      it shows that one or several other mechanisms contribute to the different grades
      of severity at the first clinical examination observed between these two
      categories of patients. We believe that HTLV-I infection acquired during
      adulthood is a marker of high-risk behavior and that it might be associated with
      early or multiple HIV infections.

PMID- 8548353
TI  - Influence of HIV epidemic on the incidence of Kaposi's sarcoma in Zambian
      children.
AB  - Acquired immunodeficiency syndrome-associated Kaposi's sarcoma (KS) is well
      documented in adults. However, very little information is available about KS in
      the pediatric age group. A retrospectively study was undertaken at the University
      Teaching Hospital (UTH), Lusaka, Zambia, to define the incidence and clinical
      profile of KS in Zambian children over the last 13 years and to determine the
      influence, if any, of the current human immunodeficiency virus (HIV) epidemic on
      the pattern of pediatric KS. All the histopathological records from 1980 to 1992
      were reviewed and all cases of KS along with the total number of malignancies,
      both in children and adults, were analyzed. Along with this, 17 of 23 case files
      of pediatric KS patients treated at the UTH since 1984 were retrieved and
      clinical details recorded. Of a total of 915 cases of KS, 85 (9.25%) were in
      children < 14 years of age. The age ranged from 7 months to 14 years, with an
      average of 5.62 years; the male/female ratio was 1.76:1. A significant increase
      in the incidence of pediatric KS has been recorded since 1987 (p < 0.001). This
      coincides with the advent of the HIV epidemic in the country. The disease was
      aggressive and fulminant in pediatric patients. More than 80% HIV seropositivity
      was detected. Children with blood transfusion-related HIV infection had cutaneous
      or lymphocutaneous disease, indicating that the mode of acquisition of HIV
      infection may influence the clinical appearance of KS. Thus, HIV-associated KS in
      children is becoming a common entity in Zambia. An urgent prospective
      epidemiologic study is needed to address this problem in HIV-affected regions.

PMID- 8548354
TI  - Papers presented at the 7th International Conference of the Inflammation Research
      Association. White Haven, Pennsylvania, September 25-29, 1994.

PMID- 8548355
TI  - Intra-articular injection of stromelysin into rabbit knees as a model to evaluate
      matrix metalloprotease inhibitors.

PMID- 8548356
TI  - Oral administration of a matrix metalloproteinase inhibitor, CGS 27023A, protects
      the cartilage proteoglycan matrix in a partial meniscectomy model of
      osteoarthritis in rabbits.

PMID- 8548357
TI  - Stromelysin expression in IL-1 beta stimulated bovine articular cartilage
      explants.

PMID- 8548358
TI  - Molecular cloning and characterization of rabbit TIMP2.

PMID- 8548359
TI  - Effects of a protein kinase C inhibitor (PKCI) on the development of adjuvant
      induced arthritis (AA) in rats.

PMID- 8548360
TI  - The influence of a peptide sequence from PF-4 (CT-112) on type II collagen
      induced arthritis in mice.

PMID- 8548361
TI  - Overexpression of the NC4 domain of type IX collagen induces osteoarthritis in
      mice.

PMID- 8548362
TI  - Induction of osteoarthritis in guinea pigs by transection of the anterior
      cruciate ligament: radiographic and histopathological changes.

PMID- 8548363
TI  - Metalloprotease inhibitors halt collagen breakdown in IL-1 induced bovine nasal
      cartilage cultures.

PMID- 8548364
TI  - Antinociceptive activities of non-steroidal antiinflammatory drugs (NSAIDs)
      following intracerebroventricular (i.c.v.) and intrathecal (i.t.) administration
      in mice.

PMID- 8548365
TI  - Identification and partial characterization of an acidic sphingomyelinase (SMase)
      from cultured human umbilical vein endothelial cells (HUVEC).

PMID- 8548366
TI  - 3(S)-hydroxy-leukotriene B4 is a potent granulocyte chemotaxin in the guinea pig
      dermis.

PMID- 8548367
TI  - Differential involvement of protein kinase C in activating cytosolic
      phospholipase A2 in alveolar macrophages and monocyte differentiated U937 cells.

PMID- 8548368
TI  - Effect of CGS 25019C and other LTB4 antagonists in the mouse ear edema and rat
      neutropenia models.

PMID- 8548369
TI  - The pharmacokinetics and metabolism of SC-53228, a specific leukotriene B4
      receptor antagonist.

PMID- 8548370
TI  - A structural feature of N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulfonamide
      (NS-398) that governs its selectivity and affinity for cyclooxygenase 2 (COX2).

PMID- 8548371
TI  - CGS 26529: the biological profile of a novel, orally active 5-lipoxygenase
      inhibitor with an extended duration of action.

PMID- 8548372
TI  - Role of induced nitric oxide synthase and increased NO levels in zymosan
      peritonitis in the rat.

PMID- 8548373
TI  - Degradation of bovine cartilage proteoglycan in vitro is enhanced by inhibition
      of nitric oxide synthase.

PMID- 8548374
TI  - Role of inducible nitric oxide synthase (iNOS) and peroxynitrite in gut
      inflammation.

PMID- 8548375
TI  - Flow cytometric assessment of NADPH oxidase inhibitors in whole blood.

PMID- 8548376
TI  - Activation of blood complement in guinea pigs receiving an intravenous injection
      of Sephadex beads.

PMID- 8548377
TI  - Time-dependent cytokine production in the croton oil-induced mouse ear oedema and
      inhibition by prednisolone.

PMID- 8548378
TI  - A novel contact hypersensitivity model for rank-ordering formulated
      corticosteroids.

PMID- 8548379
TI  - Radiological assessment of relaxin-induced pubic symphyseal changes in guinea
      pigs: a model for screening disease modifying agents for osteoarthritis.

PMID- 8548381
TI  - Specific increase of microvascular permeability in lower airways of guinea pigs
      injected with Sephadex beads.

PMID- 8548380
TI  - Granulocyte recruitment in guinea pig lungs following the administration of MBP
      like cationic protein.

PMID- 8548382
TI  - Pulmonary pharmacology of WAY-126299A: a dual-acting 5-lipoxygenase inhibitor and
      leukotriene D4 antagonist.

PMID- 8548383
TI  - Pulmonary antiallergic and antiinflammatory effects of a novel, orally-active
      phosphodiesterase IV inhibitor (WAY-127093B) in guinea pigs and rats.

PMID- 8548384
TI  - Relationship between the development of bronchial hyperresponsiveness and the
      airway eosinophilia in guinea pigs following injection with Sephadex beads.

PMID- 8548385
TI  - Differential modulation by betamethasone of allergen-induced cell influx and cell
      peroxidase in guinea-pig lungs.

PMID- 8548386
TI  - Sirolimus (rapamycin) inhibits mitogen-induced stimulation of protein synthesis
      in primary lymphocytes.

PMID- 8548387
TI  - The biochemical and pharmacological activity of 9-benzyl-9-deazaguanine, a potent
      purine nucleoside phosphorylase (PNP) inhibitor.

PMID- 8548388
TI  - CP-123,369: a potent, orally active immunosuppressive agent.

PMID- 8548389
TI  - Interferon-gamma and antibodies to interleukin-5 and interleukin-4 inhibit the
      pulmonary eosinophilia in allergic mice.

PMID- 8548390
TI  - Leflunomide: an active antiinflammatory and antiproliferative agent in models of
      dermatologic disease.

PMID- 8548391
TI  - Comparison of effects of sirolimus on cytokine dependent and cytokine independent
      proliferation.

PMID- 8548392
TI  - Evaluation of lymphocyte subsets in tamarins and marmosets.

PMID- 8548393
TI  - The modified recalcification time (MRT) test assesses suppressive effect of
      general anesthesia (GA) on monocyte function.

PMID- 8548394
TI  - Modulation of the immunoglobulin dysregulation in GvH- and SLE-like diseases by
      the murine IL-4 receptor (IL-4-R).
AB  - As has been reported previously, models of chronic graft-versus-host (GvH) and
      systemic lupus erythematosus (SLE)-like diseases are characterized by high IgE
      and IgG1 immunoglobulin (Ig) levels in the serum. An IL-4 induced pathological
      expansion of Th2 helper cells has been described for both disease models. Due to
      the immunopharmacological profile of soluble recombinant interleukin-4 receptor
      (IL-4-R) to bind specifically the corresponding ligand IL-4 and thereby to
      modulate biological activity upon exogenous administration in various autoimmune
      disease models, we investigated the immunoregulatory activity of IL-4-R and anti
      IL-4 monoclonal antibody (MAb) 11B11 on the development of SLE-like disease in
      MRL/lpr autoimmune mice and on chronic GvH reaction in BDF1 hybrid mice.
      Sensitized GvH-BDF1 hybrid mice and SLE in MRL/lpr autoimmune mice were treated
      in vivo with the IL-4 antagonists to alter the pattern of serum Ig production and
      to modulate the disease process. These animals were followed for proteinuria,
      autoantibody production (anti-dsDNA), serum IgE, IgG1 and IgG2a levels, and the
      survival was monitored. Treatment of these diseased animals resulted in an
      improved survival rate, lowered the percentage of animals with lymphadenopathy
      and hepatosplenomegaly, reduced the levels of autoantibodies and inhibited
      proteinuria of the developing glomerulonephritis in both mouse strains, even in
      the established diseases. In both models the increase in total IgE and IgG1
      levels in serum was strongly inhibited by the IL-4 antagonists, even under
      therapeutic conditions. But there was no inhibitory activity observed on the
      IgG2a serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8548395
TI  - Endotoxin negates anticoagulant effect of cyclosporine.

PMID- 8548396
TI  - Heavy water activates monocyte generation of tissue factor.

PMID- 8548397
TI  - Anti-inflammatory activity of an orally active peptide sequence from PF-4 on
      acute inflammation and DTH.

PMID- 8548398
TI  - Digoxin and endotoxin: a lethal pro-inflammatory combination.

PMID- 8548399
TI  - Modified recalcification time (MRT): a model to assess drug-induced depressed
      immune function.

PMID- 8548400
TI  - Pharmacological inhibition of CD28-stimulated T cell activation.

PMID- 8548401
TI  - Sub-therapeutic doses of sirolimus and cyclosporin A in combination reduce SLE
      pathologies in the MRL mouse.

PMID- 8548402
TI  - Leflunomide, a reversible inhibitor of pyrimidine biosynthesis?

PMID- 8548403
TI  - Ultraviolet B-induced inflammatory cytokine production, in vivo: initial
      pharmacological characterization.

PMID- 8548404
TI  - Secretion of human monocyte mature IL-1 beta: optimization of culture conditions
      and inhibition by ICE inhibitors.

PMID- 8548405
TI  - The role of ICAM-1 in the reverse passive Arthus reaction induced pleurisy in the
      rat.

PMID- 8548406
TI  - The modified recalcification time (MRT) assesses prothrombophlebitic role of
      conjugated estrogen (premarin).

PMID- 8548407
TI  - Modulation of chondrocyte proteoglycan synthesis by endogeneously produced nitric
      oxide.

PMID- 8548408
TI  - Expression and modulatory effects of heme oxygenase in acute inflammation in the
      rat.
AB  - Heme oxygenase (HO) is the rate limiting enzyme in the catabolism of heme
      molecules to the bile pigments which have recently been demonstrated to be strong
      antioxidants. In this study we analyzed the activity of HO in inflammatory cells
      isolated from a model of carrageenin induced acute inflammation in the rat. HO
      activity was significantly higher 24 hours after induction of the inflammation,
      this increase in activity coincided with the appearance of the highly inducible
      isoform of HO, Heat Shock Protein 32 kDa (HSP32) as detected by Western Blot
      analysis. Pre-treatment of animals with Tin protoporphyrin, a HO inhibitor,
      increased cell exudate at 24 hour in this model by 128% as compared to vehicle
      control. In comparison pre-treatment with a HO inducer, Ferriprotoporphyrin,
      decreased inflammatory cell number by 50% and cell exudate by 73% at 24 hours
      compared to control. These results suggest that HO may represent an endogenous
      protective mechanism against free radicals in acute inflammation and may be
      involved in the resolution of acute inflammation. The HSP32 isoform of HO may
      therefore represent a novel therapeutic target for the modulation of the
      inflammatory response.

PMID- 8548409
TI  - Decrease in scavenger receptor expression in human monocyte-derived macrophages
      treated with granulocyte macrophage colony-stimulating factor.
AB  - To determine whether scavenger receptors are susceptible to regulation by
      granulocyte macrophage colony-stimulating factor (GM-CSF), a macrophage-specific
      cytokine, human monocytes were differentiated into macrophages in the absence or
      presence of 20 U/mL GM-CSF. Binding, uptake, and degradation of acetylated LDL
      (Ac-LDL) and oxidized LDL (Ox-LDL) were measured. Treatment with GM-CSF resulted
      in a significant twofold to threefold decrease in the number of binding sites for
      Ac-LDL and Ox-LDL on the surface of macrophages without affecting the affinity of
      the receptor for these ligands. Competition experiments revealed that two binding
      sites were responsible for the recognition and uptake of Ac-LDL; one specific for
      Ac-LDL and one that recognized both Ac-LDL and Ox-LDL. No binding site specific
      for Ox-LDL could be detected in either control or GM-CSF-treated macrophages.
      Treatment of human monocyte-derived macrophages with GM-CSF resulted in a
      decrease of the Ac-LDL/Ox-LDL receptor but did not affect the binding site
      specific for Ac-LDL. Northern blot analysis showed that mRNA levels of both types
      I and II scavenger receptor were reduced in macrophages differentiated in the
      presence of GM-CSF. Human macrophages that were differentiated in the presence of
      GM-CSF accumulated approximately 50% fewer cholesteryl esters. Taken together,
      these results indicate that GM-CSF can downregulate both types I and II scavenger
      receptor in human monocyte-derived macrophages, which might have implications for
      foam cell formation.

PMID- 8548410
TI  - Genotype distribution of angiotensin-converting enzyme polymorphism in Australian
      healthy and coronary populations and relevance to myocardial infarction and
      coronary artery disease.
AB  - Angiotensin-converting enzyme is a key component of the renin-angiotensin system
      that plays an important role in cardiovascular regulation. An association between
      the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism and
      increased coronary risk has been found in some studies but not in others. To
      explore this further in an Australian white population, we compared the ACE
      genotype distribution in 550 patients aged 37 to 65 years with coronary artery
      disease documented by angiography with the genotype distribution in 404 healthy
      school children aged 6 to 13 years. We also explored associations in the patients
      between the angiotensin-converting enzyme I/D polymorphism and a history of
      myocardial infarction and coronary artery disease severity assessed by the number
      of major coronary arteries with more than 50% luminal obstructions and by the
      Green Lane coronary score. The frequencies of the angiotensin-converting enzyme
      genotype in the coronary artery disease patients were 0.236 for I/I, 0.395 for
      I/D, and 0.369 for D/D genotypes. This distribution with an excess of the D/D
      genotype was significantly different (chi 2 = 23.69, P < .0001) from that in the
      school children, in whom the genotype distribution was in Hardy-Weinberg
      equilibrium (I/I, 0.21; I/D, 0.54; D/D, 0.25). There was also a significant
      excess of D/D genotype among patients with a history of myocardial infarction
      (chi 2 = 9.42, P = .009), and there was the same D/D excess in the subgroup of
      children (n = 60) with two or more grandparents who had had coronary artery
      disease. We found no associations between the angiotensin-converting enzyme
      polymorphism and the number of significantly stenosed coronary arteries (chi 2 =
      2.069, P = .91). We conclude that the D/D genotype is a significant predictor for
      coronary artery disease events in the Australian white population but is not a
      marker for angiographically assessed coronary artery disease severity. The
      angiotensin-converting enzyme genotype-associated increased risk for coronary
      events may be mediated more by angiotensin II-induced coronary vasoconstriction
      than by an increase in injury-related smooth muscle cell proliferation in the
      coronary vasculature.

PMID- 8548411
TI  - Proliferating arterial smooth muscle cells after balloon injury express TNF-alpha
      but not interleukin-1 or basic fibroblast growth factor.
AB  - We have recently reported that balloon withdrawal injury to rabbit abdominal
      aortas induces sustained activation indicated by the expression of certain
      adhesion molecules such as vascular cell adhesion molecule-1 and intercellular
      adhesion molecule-1 in regenerating endothelial cells and/or proliferating smooth
      muscle cells (SMCs). Local cytokine signaling may contribute to ongoing
      modulation of cellular functions and proliferation of intimal SMCs after acute
      vascular injury. We therefore studied the expression of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), proinflammatory and SMC
      growth-promoting cytokines, and basic fibroblast growth factor (bFGF) in SMCs of
      rabbit aorta at 2 (n = 4), 5 (n = 4), and 10 days (n = 6) after balloon injury.
      All animals were given bromodeoxyuridine (BrdU, 10 mg/kg per day) continuously to
      label proliferating SMCs. Frozen cross sections of injured vessels at each time
      point after balloon injury were examined by immunoperoxidase staining with
      monoclonal antibodies. As early as 2 days after injury, before intimal thickening
      begins, foci of medial SMCs expressed TNF-alpha, but not all TNF-alpha-positive
      medial SMCs had incorporated BrdU, suggesting that TNF-alpha expression by medial
      SMCs may precede their proliferation. At 5 days, TNF-alpha-bearing and BrdU
      labeled medial SMCs increased in number. At 10 days after injury, when uniform
      intimal thickening occurred, almost all neointimal SMCs and foci of medial SMCs
      labeled with BrdU. Most of the BrdU-positive (proliferating) SMCs expressed
      immunoreactive TNF-alpha. Reverse transcription polymerase chain reaction showed
      increased TNF-alpha mRNA at 10 days after ballooning in the injured portion of
      the aorta. In contrast, regions of SMC proliferation showed inconsistent IL-1
      beta expression, and bFGF, abundant in normal rabbit arteries, was not detected
      in areas of SMC replication. These data indicate that replication of arterial
      SMCs after balloon injury occurs in regions of TNF-alpha but not IL-1 beta
      expression and correlates inversely with the presence of bFGF. These results
      indicate that SMC-derived TNF-alpha serves as a marker of modulated SMC phenotype
      after acute vascular injury and may contribute to local cellular activation and
      proliferation of SMCs at sites of arterial injury.

PMID- 8548412
TI  - Plasma lipoprotein(a) levels in subjects attending a metabolic ward.
      Discrimination between individuals with and without a history of ischemic stroke.
AB  - In this cross-sectional study we compared the abilities of lipoprotein(a)
      [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen
      activator (TPA) to discriminate between individuals with and without a history of
      stroke from among subjects in a metabolic ward. A total of 210 subjects (108 men
      and 102 women; mean age, 63.8 years; range, 31 to 86 years) provided plasma and
      DNA samples for the study. Of these, 51 men and 50 women had a history of
      ischemic stroke. The 109 subjects without a history of stroke were compared with
      those with such a history for major risk factors for ischemic events. Mean plasma
      TPA and PAI-1 levels significantly (P < .001) discriminated among subjects
      younger than 70 years with a history of stroke. The mean plasma Lp(a) level of
      stroke subjects (21.9 mg/dL) did not differ significantly from that of control
      subjects (15.2 mg/dL). However, among individuals < 70 years old, Lp(a) plasma
      levels > 50 mg/dL were more common among stroke patients (8 with versus 1
      without, P < .01 by chi 2 test). A molecular variation in the 5' flanking region
      of the apo(a) gene that has been related to elevated Lp(a) plasma levels (G/A
      914) was not strongly correlated with circulating levels of Lp(a), nor did Lp(a)
      levels correlate with a polymorphism of the apo(a) gene (G/A-21), which is
      strongly linked (P < .001) to the G/A-914 variation. In this setting, the
      relation between Lp(a) and cerebral ischemia appears to be limited to individuals
      below 70 years with elevated (> 50 mg/dL) plasma levels of the lipoprotein.

PMID- 8548413
TI  - Lp(a) levels and atherosclerotic vascular disease in a sample of patients with
      familial hypercholesterolemia sharing the same gene defect.
AB  - There is considerable variation in the severity of cardiovascular disease among
      patients with familial hypercholesterolemia (FH). Some reports have suggested
      that plasma lipoprotein(a) [Lp(a)] levels may explain such variation and that FH
      subjects deficient in LDL receptors, especially those with coronary heart
      disease, tend to have elevated Lp(a) levels. We have investigated the possible
      role of the LDL receptor in determining plasma Lp(a) levels in genetically
      homogeneous FH population and the contribution of Lp(a) to cardiovascular risk. A
      total of 98 FH subjects and 66 healthy first- and second-degree relatives from 30
      families with FH due to the French-Canadian > 10-kilobase deletion of the LDL
      receptor gene were studied. A reference group of 392 normolipidemic French
      Canadian participants in a Heart Health Survey was used for comparison. FH
      subjects were subdivided into subsets of 63 individuals free from atherosclerotic
      vascular disease (AVD) and 35 individuals with AVD. A complete cardiovascular
      evaluation was performed, and plasma lipid, lipoprotein, and Lp(a) levels were
      measured in all subjects in the absence of medication. Apolipoprotein (a)
      [apo(a)] phenotype was determined in 112 of FH and non-FH subjects. The log
      transformed values for plasma Lp(a) were not significantly different among the
      three groups: 0.98 +/- 0.54 (mean +/- SD) in FH subjects with AVD, 0.89 +/- 0.51
      in FH subjects without AVD, and 0.82 +/- 0.64 in their relatives. The
      distribution of the apo(a) phenotypes did not differ between the FH and non-FH
      groups. Comparison of two age- and sex-matched subgroups of FH subjects, with and
      without AVD, failed to show any differences in Lp(a) level. However, mean Lp(a)
      log values in the reference group (n = 392) were significantly lower than values
      obtained for the total FH group (0.79 +/- 0.57 versus 0.92 +/- 0.52,
      respectively; P < .05) but were not different from those of the unaffected family
      members. Thus, in our sample, the LDL receptor appears not to influence plasma
      Lp(a) levels; rather, these levels reflect shared apo(a) genes. The
      cardiovascular risk in this group of subjects with FH was related to age, male
      sex, total and LDL cholesterol, and higher apoB but not Lp(a) levels.

PMID- 8548414
TI  - Effects of simvastatin on plasma lipids and apolipoproteins in familial
      hypercholesterolemic swine.
AB  - Familial hypercholesterolemia (FHC) in swine, which resembles human familial
      combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated
      with the development of severe coronary lesions similar to those occurring in
      advanced human coronary disease. The disorder is characterized by elevated plasma
      total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C),
      apolipoproteins (apo) B, C-III, and E, and by decreased levels of HDL-cholesterol
      (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose
      response study with simvastatin, a specific inhibitor of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment
      groups of FHC animals, exhibiting TC > or = 250 mg/dL. The animals were fed 0,
      80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters
      included the levels of TC, VLDL-C, LDL-C, HDL-C, TG, lathosterol, apoA-I, B, C
      III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly
      decreased the levels of TC (-25%), LDL-C (-27%), lathosterol (-40%), apoB (-22%),
      apoC-III (-37%), and apoE (-24%) and modestly decreased the levels of HDL-C (
      12%) and apoA-I (-11%) (percent relative to the average pretreatment and
      posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the
      lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were
      also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200
      mg/d, while the other parameters were not influenced at these doses. The
      simvastatin-induced decreases of LDL-C, HDL-C, and apoA-I, B, C-III, and E were
      significantly correlated among each other. These results show that the trend of
      responses in TC, LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swine
      is similar to that observed in humans, although the drugs is less potent and
      efficacious in swine, while the results are different from those in humans with
      regard to the remaining parameters.

PMID- 8548415
TI  - Association between serum fibrinogen concentrations and HDL and LDL subfraction
      phenotypes in healthy men.
AB  - Hyperfibrinogenemia and a dyslipoproteinemia characterized by reduced HDL2
      cholesterol and elevated levels of small, dense LDL particles are risk factors
      for coronary artery disease. However, the relationship between fibrinogen and
      lipoproteins, in particular LDL subfractions, is uncertain. We therefore measured
      serum fibrinogen levels and serum concentrations of cholesterol and
      apolipoproteins of VLDL, IDL, six LDL, and two HDL subfractions by using the
      technique of density-gradient ultracentrifugation in 132 nonsmoking men without
      evidence of coronary artery disease or infection. Dividing the individuals into
      quartiles according to their fibrinogen values showed that men within the highest
      fibrinogen quartile (fibrinogen 2.90 to 4.34 g/L) had significantly higher
      concentrations of small, dense LDL (d > 1.044 g/mL) apolipoprotein B and
      cholesterol and lower concentrations of HDL2 cholesterol than men within the
      lower fibrinogen quartiles (fibrinogen < 2.55 g/L). Multivariate regression
      analysis revealed that the association between fibrinogen and small, dense LDL
      particles was independent of serum triglycerides, cholesterol, body mass index,
      and age. In contrast, the relationship between fibrinogen and HDL2 cholesterol
      was primarily influenced by triglycerides and cholesterol and not independently
      influenced by fibrinogen. There were no significant differences between the
      quartiles in terms of insulin, glucose, insulin resistance, free fatty acids,
      lipoprotein(a), and blood pressure. This study showed that fibrinogen is
      associated with the expression of a more atherogenic LDL subfraction phenotype
      independent of body mass index, age, other serum lipids, and insulin resistance
      in a healthy male nonsmoking population. The reason for this association is
      uncertain. These findings reinforce the evidence that fibrinogen should be
      determined when assessing coronary risk.

PMID- 8548416
TI  - Plasma concentration of apolipoprotein E in intermediate-sized remnant-like
      lipoproteins in normolipidemic and hyperlipidemic subjects.
AB  - Triglyceride-rich lipoprotein (TRL) remnants have been strongly implicated in the
      pathogenesis of atherosclerosis. To further investigate plasma remnant
      lipoprotein metabolism, we have determined the plasma concentration of
      apolipoprotein (apo) E (by polyclonal enzyme-linked immunoassay) in remnant-like
      lipoproteins, isolated by automated gel filtration chromatography as a fraction
      intermediate in size between VLDL and HDL. In normolipidemic subjects (n = 12),
      1.2 +/- 0.11 mg/dL (33 +/- 2%, mean +/- SE) of total plasma apoE was associated
      with this fraction (termed ISL apoE). In hypercholesterolemic (type IIa, n = 12),
      hypertriglyceridemic (type IV, n = 12), and mixed hyperlipidemic (type IIb, n =
      12) subjects, mean ISL apoE concentrations were 2.1 +/- 0.2, 2.5 +/- 0.2, and 3.8
      +/- 0.4 mg/dL, respectively (P < .001 versus normal values) (45 +/- 2%, 32 +/-
      2%, and 44 +/- 2% of total). ISL apoE was 8.7 +/- 1.4 mg/dL (42 +/- 3%) in type
      III dyslipidemic subjects (apoE2/2, n = 8). ISL apoE was positively correlated
      with plasma triglyceride (r = .41, P < .01), and at any given level of plasma
      triglyceride, subjects with an apoE2/2 or apoE3/2 phenotype tended to have a
      higher concentration of ISL apoE (P < .01) than apoE3/3 or E4/3 individuals. ISL
      apoE was also correlated (P < .001) with total plasma cholesterol (r = .66), TRL
      cholesterol (r = .49), TRL apoE (r = .47), LDL apoB (r = .42), and LDL+HDL
      triglyceride (r = .74). These results suggest that (1) a significant proportion
      of plasma apoE resides within an intermediate-sized remnant-like lipoprotein
      fraction in both normolipidemic and hyperlipidemic subjects; (2) plasma remnant
      lipoprotein accumulation is associated with an elevation in ISL apoE
      concentration; and (3) ISL apoE concentration is significantly correlated with
      various proatherogenic lipid parameters and may itself be a potentially important
      atherogenic index.

PMID- 8548417
TI  - Sex differences in coagulation and fibrinolysis in white subjects with non
      insulin-dependent diabetes mellitus.
AB  - The increase in cardiovascular risk associated with having non-insulin-dependent
      diabetes mellitus (NIDDM) is far greater in women than men. Conventional risk
      factors do not account for this excess, and attention has focused on the possible
      contribution of abnormalities of fibrinolysis and coagulation in NIDDM. In the
      general population a number of hemostatic factors have been shown to predict the
      occurrence or progression of coronary artery disease. To investigate sex
      differences in coagulation and fibrinolysis in NIDDM, we measured levels of
      fibrinogen, factor VII:C, von Willebrand factor, plasminogen activator inhibitor
      1, and tissue plasminogen activator in 213 NIDDM subjects (124 men and 89 women)
      who were not receiving insulin therapy. The women had higher levels of factor
      VII:C (144% versus 120.5% in men, P < .0005) and plasminogen activator inhibitor
      1 activity (25.6 versus 17.0 U/mL), and these differences remained significant
      when account was taken of the higher body mass index (29.6 versus 28.0 kg/m2, P =
      .02), glycosylated hemoglobin (7.2% versus 6.8%, P < .05), and cholesterol levels
      (6.3 versus 5.7 mmol/L, P < .0005) in women than men. In contrast, levels of
      fibrinogen (3.2 versus 3.1 g/L), tissue plasminogen activator antigen (10.6
      versus 11.2 ng/mL), and von Willebrand factor (1.27 versus 1.23 IU/mL) were no
      different between women and men, respectively. These results suggest that
      elevated levels of plasminogen activator inhibitor-1 and factor VII:C may
      contribute to the increased cardiovascular risk of NIDDM that is particularly
      marked in women.

PMID- 8548418
TI  - Plasma homocysteine and severity of atherosclerosis in young patients with lower
      limb atherosclerotic disease.
AB  - Elevated plasma homocysteine levels are recognized as an independent risk factor
      for atherosclerotic disease. It is not known (1) whether the severity of
      atherosclerotic disease is related to hyperhomocyst(e)inemia or (2) whether any
      such relation differs between fasting and post-methionine loading plasma
      homocysteine levels. Therefore, in 171 consecutive patients under 55 years of age
      with first symptoms of lower-limb disease, we examined the relation between
      severity of atherosclerosis and plasma homocysteine concentration. Severity of
      atherosclerotic disease was estimated from the prevalence of coronary artery
      disease and cerebrovascular disease and from the angiographic extent of lower
      limb disease. Plasma homocysteine was measured after a period of fasting and in
      response to methionine loading (0.1 g/kg). In multivariate analysis, the
      prevalence of coronary artery disease plus cerebrovascular disease was related to
      both fasting and postmethionine homocysteine levels (odds ratio [OR] for the
      upper quartile versus the lower three quartiles, 2.8, 95% confidence interval
      [CI], 1.1 to 7.5; and OR 3.0, 95% CI, 1.1 to 7.8, respectively). The extent of
      lower-limb disease was weakly related to the fasting homocysteine level (partial
      correlation coefficient, .12; P = .17) and more strongly related to the
      postmethionine homocysteine level (partial correlation coefficient, .25; P =
      .003). These relations tended to be more pronounced in women than in men. They
      were independent of age, total serum cholesterol, blood pressure, and smoking
      habit. We concluded that the severity of atherosclerotic disease in young
      patients with lower-limb atherosclerotic disease is associated with high
      postmethionine and fasting homocysteine concentrations.

PMID- 8548419
TI  - Blood velocity profiles in the human renal artery by Doppler ultrasound and their
      relationship to atherosclerosis.
AB  - Blood velocity profiles were measured in the renal branch (diameter 5.9 +/- 1.3
      mm) of the aortorenal bifurcation using a 20-MHz 80-channel pulsed Doppler
      velocimeter during retroperitoneal surgery in 10 patients. The peak Reynolds
      number was 1145 +/- 140 and the frequency parameter (Wormersley parameter) was
      3.0 +/- 0.8. Immediately distal to the ostium of the renal artery, reverse flow,
      indicating flow separation, was observed near the cranial wall mainly during the
      first part of the cardiac cycle. There were flows from the cranial to the caudal
      side of the artery at this location, indicating the presence of strong secondary
      flows. Two diameters downstream of the ostium, the velocity profiles were skewed
      to the caudal side in all patients. Four diameters downstream, the flow profile
      was symmetrical (3 patients) or only slightly skewed (7 patients) and virtually
      parabolic throughout the cardiac cycle. These observations mean that the flow on
      the cranial side of the renal branch of the human aortorenal bifurcation is
      characterized by (1) a bidirectional oscillation of the flow, (2) separation of
      the flow during systole, and (3) low time-averaged shear rate. These blood
      velocity patterns may be related to the localization and development of
      atheromatous plaque that occurs preferentially in this region of the renal
      artery. Conversely, the unidirectional, axisymmetrical flow found in more distal
      parts of the renal artery are associated with a very low incidence of lesions.

PMID- 8548420
TI  - A method for the assessment of hypoxia in the arterial wall, with potential
      application in vivo.
AB  - According to the anoxemia theory of atherosclerosis, an imbalance between the
      demand for and supply of oxygen in the arterial wall is a key factor in the
      development of atherosclerotic lesions. Direct in vitro and in situ measurements
      have shown that PO2 is decreased in the inner part of the media, but the degree
      of hypoxia in vivo or the distribution of hypoxia along the arterial tree is not
      known. We applied a hypoxia marker, 7-(4'-(2-nitroimidazol-1-yl)-butyl)
      theophylline (NITP), to develop a method for the detection of hypoxia in the
      arterial wall. Immunoperoxidase and immunofluorescence were used to detect the
      marker, and a clearly PO2-dependent staining was observed in the media of rabbit
      and swine aorta in vitro. The cutoff PO2 level was probably around 2 to 3 mm Hg.
      In experimental atherosclerotic lesions in the rabbit the marker seemed to bind
      to foam cells that were already at a higher surrounding PO2, which might reflect
      a higher local oxygen consumption. The binding of the marker to endothelial cells
      was not PO2 dependent. One explanation for this finding could be that the marker
      was metabolized via a non-oxygen-dependent pathway in these cells. We propose
      that this method may be used to assess arterial wall hypoxia in vivo.
      Furthermore, the spatial resolution allows the detection of local variations
      within the arterial tree.

PMID- 8548421
TI  - Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with
      interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta.
AB  - Recent studies have documented evidence for the death of smooth muscle cells
      (SMCs) within advanced human atheroma. These lesions contain macrophages and T
      lymphocytes in addition to SMCs. We therefore investigated whether interferon
      gamma (IFN-gamma), a cytokine secreted by T lymphocytes, or interleukin-1 beta
      (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), two cytokines
      characteristically produced by activated macrophages, can trigger apoptosis of
      vascular SMCs. Simultaneous treatment with IFN-gamma and TNF-alpha and/or IL-1
      beta but not with each cytokine alone promoted death of human and rat SMCs.
      Exposure for 48 hours to a combination of IFN-gamma (400 U/mL), TNF-alpha (400
      U/mL), and IL-1 beta (100 U/mL) significantly (P < .001) increased the
      accumulation of oligonucleosomes comprising DNA fragments and histones in human
      SMCs. Electrophoresis of genomic DNA showed internucleosomal fragments of genomic
      DNA isolated from the cytokine-cotreated SMCs of both humans and rats. These
      cells exhibited morphological changes typical of apoptosis, including cell
      shrinkage, membrane blebbing, chromatin condensation, and nuclear fragmentation.
      In situ 3' end labeling of DNA fragments with terminal transferase confirmed the
      fragmentation of genomic DNA in these cells. Simultaneous treatment with IFN
      gamma and TNF-alpha or IL-1 beta induced elaboration of nitrite, an end product
      of nitric oxide, in rat but not human SMCs. NG-monomethyl-L-arginine inhibited
      nitrite accumulation and also partly blocked cytokine-induced apoptosis of rat
      SMCs but had little effect on human SMCs, suggesting operation of both nitric
      oxide-dependent and -independent mechanisms for cytokine-induced apoptosis in
      vascular SMCs. Production of immune cytokines by vascular cells and/or
      infiltrating leukocytes may regulate apoptotic death of SMCs during
      atherogenesis.

PMID- 8548422
TI  - Regulation of vascular smooth muscle cell migration and proliferation in vitro
      and in injured rat arteries by a synthetic matrix metalloproteinase inhibitor.
AB  - Smooth muscle cell (SMC) migration and proliferation and extracellular matrix
      remodeling are essential aspects of the arterial response to injury, vessel
      development, and atherogenesis. Matrix metalloproteinase (MMP) expression is
      associated with SMC proliferation and migration after arterial injury. To assess
      the role of MMPs in SMC proliferation and migration and intimal thickening, we
      measured the effect of the synthetic MMP inhibitor BB94 (Batimastat) on DNA
      synthesis and migration of SMCs in vitro as well as the formation of a neointima
      after balloon injury to the rat carotid artery. BB94 dose-dependently inhibited
      SMC migration induced by platelet-derived growth factor (PDGF)-BB through a
      filter coated with a thick basement membrane matrix (Matrigel) layer but did not
      show any inhibitory effect on SMC migration through a lightly coated filter. At
      concentrations up to 1 mumol/L, BB94 did not alter DNA synthesis induced by PDGF
      AA or PDGF-BB. Treatment with 30 mg BB94.kg-1.d-1 IP for 7 or 14 days after
      balloon injury to the rat carotid artery decreased the total number of intimal
      SMC nuclei and suppressed intimal thickening. SMC proliferation (5-bromo-2'
      deoxyuridine labeling) was decreased in the media at 2 days, whereas it was
      increased in the intima at 7 but not 14 days. These results suggest that BB94
      inhibits intimal thickening after arterial injury by decreasing SMC migration and
      proliferation and support the conclusion that MMPs play a significant role in
      regulating intimal thickening in injured arteries.

PMID- 8548424
TI  - Development of the lipid-rich core in human atherosclerosis.
AB  - In recent years the role of the atherosclerotic core in promoting plaque rupture
      has become well recognized. A new insight into core development is its
      origination early in atherogenesis, before formation of the fibrous plaque. The
      early core is associated with accumulation of vesicular lipid rich in free
      cholesterol. Later in core development, lipid deposits become more diverse. The
      weight of evidence points toward a direct extracellular process, probably
      lipoprotein aggregation and fusion, as the chief pathway of cholesteryl ester
      accumulation, although foam cell death may also contribute cholesteryl ester. The
      mechanism or mechanisms of formation of vesicular, cholesterol-rich deposits are
      unknown. Since the increase in free cholesterol is likely to have deleterious
      effects on cells bordering the core, the further elucidation of cellular and
      biochemical pathways leading to and responding to free cholesterol accumulation
      is of great importance. Complement activation and cellular stress responses are
      prominent in the vicinity of core lipids, but their pathogenetic roles remain to
      be established. Since the core appears so early in atherogenesis, these as well
      as other, yet to be determined cellular responses to core lipids, oxidized and
      unoxidized, could have a considerable effect on overall lesion development. Much
      remains to be learned about macrophage and smooth muscle responses,
      calcification, capillarization, and matrix protein alterations in the evolution
      of the core and surrounding arterial intima.

PMID- 8548423
TI  - Time course of cellular proliferation, intimal hyperplasia, and remodeling
      following angioplasty in monkeys with established atherosclerosis. A nonhuman
      primate model of restenosis.
AB  - Animal models of arterial injury have failed to predict effective therapy to
      prevent restenosis in humans. While this may relate to species differences in the
      control of smooth muscle cell growth, many studies have used nonatherosclerotic
      animals, thereby failing to consider the importance of atherosclerosis in the
      response to injury. In an attempt to model human restenosis more accurately, we
      characterized the response to angioplasty in atherosclerotic monkeys. Twenty-one
      cynomolgus monkeys were fed an atherogenic diet for 36 months (plasma
      cholesterol, 12 +/- 1 mmol/L [470 +/- 23 mg/dL]). Angioplasty was then performed
      in the left iliac artery. After 4, 7, 14, or 28 days, bromodeoxyuridine was given
      to label proliferating cells, and iliac arteries were fixed in situ at
      physiological pressure (5 or 6 animals at each time point). Comparisons were made
      between injured and uninjured iliac arteries within each animal. Angioplasty
      often fractured the intimal plaque and media, transiently increasing lumen
      caliber (4 days: lumen area, 232.5 +/- 80.3% of control) and artery size as
      reflected by external elastic lamina area (EEL). EEL and lumen caliber returned
      to baseline by 7 days. Proliferation was increased throughout the artery wall at
      4 and 7 days and later declined to control rates (4 days, injured versus
      uninjured: adventitia, 45.0 +/- 6.2% versus 16.3 +/- 7.2%; media, 8.6 +/- 2.6%
      versus 0.6 +/- 0.1%; intima, 16.0 +/- 5.6% versus 7.8 +/- 3.1%). The intima
      thickened markedly from 14 to 28 days, but an increase in EEL generally prevented
      further loss of the short-term gain in lumen caliber (28 days, percent of
      control: intimal area, 342.8 +/- 88.9%; EEL area, 150.2 +/- 28.9%; lumen area,
      119.3 +/- 21.3%). The response to angioplasty in atherosclerotic monkeys appears
      to closely resemble that in humans. Plaque fracture, delayed recoil, intimal
      hyperplasia, and remodeling may each be important in determining late lumen
      caliber. This primate model should prove valuable in defining cellular and
      biochemical mediators of human restenosis.

PMID- 8548425
TI  - Regression or progression. Dependency on vascular nitric oxide.
AB  - We have shown that chronic administration of the nitric oxide (NO) precursor L
      arginine inhibits atherogenesis in the hypercholesterolemic rabbit. However, the
      effect of supplemental arginine on preexisting lesions is not known and was the
      focus of the present study. New Zealand White rabbits received normal chow or
      0.5% cholesterol chow for 10 weeks. Subsequently, L-arginine (2.25% in drinking
      water; ARG group) or vehicle (CHOL group) was administered for an additional 13
      weeks, while the high-cholesterol diet was continued. Thoracic aortae were
      harvested at weeks 10, 14, 18, or 23. Rings of aorta were used to assess NO
      dependent vasodilation to acetylcholine. Maximal relaxation to acetylcholine in
      the CHOL rabbits became progressively attenuated from 53.4% (at week 10) to 17.4%
      (by week 23). Planimetry of the luminal surface of the aortae from CHOL animals
      revealed a progressive increase in lesion surface area from 30.3% (at week 10) to
      56.5% (by week 23). By contrast, animals in the ARG groups manifested improved
      endothelium-dependent relaxation associated with a reduction of lesion surface
      area at 14 and 18 weeks. The arginine-induced improvement in endothelium
      dependent relaxation was associated with an increased generation of vascular NO
      and a reduced generation of vascular superoxide anion. By 23 weeks, 3 of 7 ARG
      animals had persistent improvement in NO-dependent vasodilation and exhibited a
      further reduction of lesion surface area tc 5.4%. We conclude that
      hypercholesterolemia induces a progressive loss of NO-dependent vasodilation
      associated with progressive intimal lesion formation. Administration of L
      arginine to animals with preexisting intimal lesions augments vascular NO
      elaboration, reduces superoxide anion generation, and is associated with a
      reduction in lesion surface area. This is the first demonstration that
      restoration of NO activity can induce regression of preexisting intimal lesions
      and provides evidence that L-arginine therapy may be of potential clinical
      benefit.

PMID- 8548426
TI  - Platelet activation in acute myocardial infarction and unstable angina is
      inhibited by nitric oxide donors.
AB  - Platelet activation and thrombus formation within the coronary artery are major
      factors in acute myocardial infarction (AMI) and unstable angina (UA), and
      continuing platelet activation is associated with an adverse prognosis. We
      assessed platelet activation by using flow cytometry to measure platelet surface
      expression of P-selectin and glycoprotein IIb/IIIa in 20 patients with AMI and 20
      with UA, all of whom were treated with aspirin. Platelet studies were repeated
      after the infusion of a nitric oxide donor (glyceryl trinitrate or S
      nitrosoglutathione) that produced a fall in mean arterial pressure of no more
      than 10 mm Hg. P-selectin was expressed on 2.5% (range, 1.4% to 6.3%) of
      platelets from AMI and 2.3% (range, 1.6% to 3.3%) from UA subjects compared with
      1.0% (range, 0.6% to 1.9%) of platelets from 20 control volunteers without angina
      (P < .001). Glycoprotein IIb/IIIa expression was 101.6 +/- 2.7 arbitrary units of
      relative fluorescence in AMI and 100.2 +/- 3.3 in UA compared with 87.8 +/- 2.5
      in control subjects (P < .01). In both AMI and UA, S-nitrosoglutathione reduced P
      selectin (P < .001) and glycoprotein IIb/IIIa (P < .05) expression, as did
      glyceryl trinitrate (P < .02 and P < .01, respectively). In 3 of 20 patients
      receiving glyceryl trinitrate the lowest dose was not tolerated due to headache
      or hypotension. These findings show that platelet activation persists in AMI and
      UA despite aspirin treatment and that this can be inhibited by using glyceryl
      trinitrate or S-nitrosoglutathione. S-nitrosoglutathione is better tolerated at
      the doses required.

PMID- 8548427
TI  - Optimal antagonism of GPIIb/IIIa favors platelet adhesion by inhibiting thrombus
      growth. An ex vivo capillary perfusion chamber study in the guinea pig.
AB  - To evaluate the involvement of the glycoprotein (GP) IIb/IIIa-dependent process
      in platelet deposition and thrombus growth on capillaries coated with human type
      III collagen, the effects of incremental doses of Lamifiban, a potent specific
      synthetic GPIIb/IIIa antagonist, were studied in ex vivo capillary perfusion
      chambers using guinea pig blood. In this model, nonanticoagulated blood was
      perfused for 4.5 minutes at three shear rates: 100, 650, and 1600 s-1. Platelet
      deposition was quantified by computer-assisted morphometry and expressed as
      platelet adhesion (percentage of capillary surface covered with spread and
      contact platelets and platelets implicated in thrombus), mean thrombus height,
      and total thrombus cross-sectional area. In control untreated guinea pigs,
      platelet adhesion and thrombus height were 63% and 2.5 microns at 100 s-1, 60.5%
      and 13.8 microns at 650 s-1, and 45% and 28.1 microns at 1600 s-1, respectively.
      At 100 s-1, Lamifiban had no effect on platelet deposition at any of the three
      doses administered to the guinea pigs (0.3, 1, and 3 mg/kg). At 0.3 mg/kg and
      shear rates of 650 and 1600 s-1, Lamifiban had no effect on platelet adhesion or
      thrombus size, but at 1 and 3 mg/kg and shear rates of 650 and 1600 s-1, it
      significantly reduced thrombus size. At 1600 s-1, 1 mg/kg Lamifiban significantly
      increased platelet adhesion from 45% to 62.5%, whereas at 3 mg/kg it induced a
      significant overall decrease from 45% to 25% and qualitatively increased the
      ratio of contact to spread platelets. These data suggest that at high shear
      rates, GPIIb/IIIa participates in platelet spreading and that there is a balance
      between platelet involvement in adhesion to the thrombogenic surface and the
      growth of the already formed thrombus. This indicates that important clinical
      implications of an optimal therapeutic degree of GPIIb/IIIa antagonism could be
      expected.

PMID- 8548428
TI  - Adhesion of blood platelets is inhibited by VCL, a recombinant fragment
      (leucine504 to lysine728) of von Willebrand factor.
AB  - VCL, fragment Leu504 to Lys728 of von Willebrand factor (vWF) expressed in
      Escherichia coli, contains the glycoprotein (GP) Ib-binding domain of vWF. This
      fragment inhibited ristocetin-induced platelet aggregation with an IC50 of 0.2
      mumol/L and botrocetin-induced platelet aggregation with an IC50 of 0.08 mumol/L.
      We studied the antiadhesive profile of VCL by adding it to blood that was
      circulated over various adhesive surfaces. VCL inhibited adhesion to endothelial
      cell matrix, which served as a model of the vessel wall. Maximal inhibition at a
      high shear rate of 1600 s-1 was stronger (60%) than at a low shear rate of 300 s
      1 (40%). Half maximal inhibition was found to be 1.5 mumol/L at both shear rates.
      The role of various adhesive molecules was investigated in more detail by coating
      glass coverslips with collagen type I, laminin, fibronectin, or vWF. Fibrinogen
      was studied as well. Platelet adhesion to laminin and vWF was not inhibited by
      VCL. Adhesion to collagen, fibronectin, and fibrinogen was particularly inhibited
      at a high shear rate. VCL coated to a coverslip caused a concentration-dependent
      adhesion that was blocked by antibodies against GPIb, which block interaction
      with vWF. Binding studies showed a nonsaturable ristocetin binding of VCL to
      platelets that was blocked by vWF or inhibitory antibodies against GPIb. Binding
      to collagen was weak, and VCL did not inhibit binding of vWF at a 5000-fold
      excess. From these data, we conclude that VCL inhibits adhesion in all cases in
      which adhesion is vWF dependent by competing for vWF binding to activated GPIb.
      The lack of inhibition of adhesion to vWF as a single molecule may be explained
      by assuming that this adhesion is determined by interaction of nonactivated GPIb
      with vWF that has been changed in conformation by adsorption. Studies
      investigating thrombus formation on the connective tissue of an atherosclerotic
      plaque in a human coronary artery showed that VCL was able to partially prevent
      this thrombus formation. VCL may be of value in preventing adhesion and thrombus
      formation under conditions in which these processes are dependent on vWF.

PMID- 8548429
TI  - Factor VII gene polymorphisms contribute about one third of the factor VII level
      variation in plasma.
AB  - To assess the role of genetic variation in determining factor VII (FVII) activity
      and antigen levels we studied a polymorphism located in the 5' region of the gene
      (5'F7), an intronic mutation (IVS7), and the 353Arg-Gln polymorphism. All the
      polymorphisms, which showed strong allelic association, analyzed separately or in
      combination by the one-way analysis of variance, were associated with
      significantly different FVII levels. The 5'F7 and 353Arg-Gln polymorphic systems,
      which have very similar allele frequencies, contributed to a similar extent to
      the total phenotypic variance, whereas the contribution of the IVS7 polymorphism
      was lower. Genetic variation at the FVII locus, evaluated on combined genotypes,
      accounted for up to 40% of the phenotype FVII variance. As also shown by the two
      way analysis of variance, the use of two out of three markers is advisable, and
      since the 5'F7 polymorphism can be screened by a simple immunoassay, it should be
      preferred for population-based studies. No substantial differences between FVII
      activity and FVII antigen levels were found, thus suggesting that the variation
      was due to biosynthesis- or stability-mediated mechanisms. The genetic control of
      FVII levels described in this study plays an important role in determining plasma
      FVII level variability, which may influence the hemostatic balance.

PMID- 8548430
TI  - Levels of factor VIIc associated with decreased tissue factor pathway inhibitor
      and increased plasminogen activator inhibitor-1 in dyslipidemias.
AB  - Tissue factor pathway inhibitor (TFPI), a kunitztype inhibitor of the extrinsic
      coagulation pathway, factor VII coagulant (FVIIc), FVIIa, and the fibrinolytic
      factors plasminogen activator inhibitor-1 (PA1-1) and tissue plasminogen
      activator (TPA) have been studied in various hyperlipidemias. Compared with a
      normal lipidic group, mean TFPI activity was 70% higher (P < .001) and 36% higher
      (P < .001) in type IIa and IIb hyperlipidemias, respectively, and was lower by
      13% in type IV hyperlipidemia (P = .05). TFPI was correlated with LDL cholesterol
      (P < .001), total cholesterol (P < .001), HDL cholesterol (P < .01),
      apolipoproteins (apo) AI (P < .001) and B (P < .001) and lipoprotein a (P < .01).
      TFPI was negatively correlated with the triglyceride level (P < .05); the
      correlation was dependent on LDL cholesterol and HDL cholesterol levels, which
      were decreased in type IV hyperlipidemia. FVIIc activity (P < .001) was increased
      by 30% in both type IV and type IIb hyperlipidemia and was correlated with
      triglyceride levels. FVIIa was not significantly increased in any group compared
      with control group. FVIIc was correlated with triglyceride level (P < .001),
      while FVIIa was not. Interestingly, FVIIa was correlated with FVIIc (r = .5, P <
      .001) in the control group as well as in the hyperlipidemic groups (r = .32, P <
      .01). These results favor the hypothesis that higher FVIIc concentrations in
      hyperlipidemic patients are likely due to enhancement of synthesis of FVII and
      that a part of this FVII circulates in an activated chemical form. Compared with
      the control group, PAI-1 activity was twofold higher (P < .08) in type IIa
      hyperlipidemia, threefold higher (P < .001) in type IIb hyperlipidemia, and
      fourfold higher in type IV hyperlipidemia (P < .001). PAI-1 activity correlated
      with triglyceride levels (P < .001), apoB levels (P < .001) and total cholesterol
      levels (P < .05). These correlations were dependent on apoB and probably reflect
      the correlation between PAI-1 and VLDL. In contrast, TPA level was normal in the
      different hyperlipidemias. No correlation was found between TFPI, FVIIc, and PAI
      1. Variation of TFPI activity appears to be related to the variations of its main
      lipoprotein carriers: LDL, HDL, and Lp (a). The association in hypertriglycemic
      patients of hypercoagulability (increased FVIIc and decreased TFPI) and
      hypofibrinolysis (increased PAI-1) may explain thrombosis predisposition of some
      of these patients. However, it would be interesting to study the increased levels
      of endothelium-derived TFPI in plasma induced by the injection of heparin.

PMID- 8548431
TI  - Monounsaturated fatty acid-enriched diet decreases plasma plasminogen activator
      inhibitor type 1.
AB  - An increase in levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is
      one of the main hemostatic alterations in patients with coronary heart disease.
      Despite growing interest in the fibrinolytic system, few studies have been
      undertaken to determine the effect exerted on it by the different dietary fatty
      acids. We investigated the effect of a monounsaturated fat (MUFA)-rich diet in
      comparison with a low-fat diet (National Cholesterol Education Program step 1
      diet) (NCEP-1) on factors involved in blood coagulation and fibrinolysis. We also
      determined the effect of dietary cholesterol on these blood parameters. Twenty
      one young, male, healthy volunteers followed two low-fat/high-carbohydrate diets
      (< 30% fat, < 10% saturated fat, 14% MUFA) for 24 days each, with 115 or 280 mg
      of cholesterol per 1000 kcal per day, and two oleic acid-enriched diets (38% fat,
      24% MUFA) with the same dietary cholesterol as the low-fat/high-carbohydrate
      diets. Plasma levels of fibrinogen, thrombin-antithrombin complexes, prothrombin
      fragments 1+2, plasminogen, alpha 2 antiplasmin, and tissue plasminogen activator
      were not significantly different among the experimental diets used in this study.
      Consumption of the diet rich in MUFA resulted in a significant decrease in both
      PAI-1 plasma activity (P < .005) and antigenic PAI-1 (P < .04) compared with the
      carbohydrate-rich diet (NCEP-1). The addition of dietary cholesterol to each of
      these diets did not result in any significant additional effect. Changes in
      insulin levels and PAI-1 activity were positively correlated (r = .425; P < .02).
      In conclusion, consumption of diets rich in MUFAs decreases PAI-1 plasma
      activity, which is accompanied by a parallel decrease in plasma insulin levels.

PMID- 8548432
TI  - Plasminogen activator inhibitor type-1 synthesis and mRNA expression in HepG2
      cells are regulated by VLDL.
AB  - The effect of VLDL on plasminogen activator inhibitor type 1 biosynthesis in
      HepG2 cells was investigated. Exposure of HepG2 cells to VLDL (range, 10 to 100
      micrograms protein per milliliter) for 16 hours resulted in an enhanced release
      of PAI-1 antigen and PAI activity into conditioned medium, accompanied by the
      accumulation of intracellular triglycerides. By using a monoclonal antibody (IgG
      C7) specific to the LDL receptor, we showed that the effect of VLDL is mediated
      by its interaction with the LDL receptor. Enhanced PAI-1 release was due to
      increased biosynthesis: PAI-1 mRNA was doubled, mainly because of the effect on
      the 2.2-kb PAI-1 mRNA rather than the 3.2-kb transcript. Addition of insulin with
      the VLDL further enhanced PAI-1 antigen release and PAI-1 mRNA accumulation. The
      effect of VLDL on steady state levels of PAI-1 mRNA was apparently not due to an
      increase of gene transcription but to stabilization of both PAI-1 mRNA
      transcripts. The enhancing effect of VLDL on PAI-1 biosynthesis in HepG2 cells
      may raise PAI-1 antigen levels not only in hypertriglyceridemic states but also
      in those conditions in which both insulin and VLDL are elevated.

PMID- 8548433
TI  - Angiotensin II-modified LDL is taken up by macrophages via the scavenger
      receptor, leading to cellular cholesterol accumulation.
AB  - The incidence of myocardial infarction is significantly higher in hypertensive
      patients with increased plasma concentration of angiotensin (Ang) II. Ang II was
      shown to bind to LDL in vitro, and in the present study we showed its binding to
      LDL in vivo. Ang II (10(-7) mol/L) was incubated with LDL for 3 hours at 37
      degrees C, followed by reseparation of the modified lipoprotein (Ang II-LDL) and
      its incubation with J-774 A.1 macrophages. Binding of Ang II to LDL significantly
      increased the lipoprotein protein degradation (by 25%) and its cell association
      (by 75%) compared with nontreated LDL. Unlike Ang II-LDL, both Ang I-LDL and Ang
      III-LDL were taken up by macrophages similar to native LDL. The lipid composition
      and size of Ang II-LDL were similar to those of native LDL, and it was not
      aggregated. Ang II-LDL was not oxidized, as the contents of malondialdehyde and
      peroxides were not different from those found in native LDL. On heparin-Sepharose
      column chromatography, Ang II-LDL was eluted in the void volume, like acetylated
      LDL (Ac-LDL) and unlike native LDL, which binds to heparin. The cellular
      degradation of Ang II-125I-labeled LDL by J-774 A.1 macrophages of Ang II-125I
      labeled LDL by J-774 A.1 macrophages was studied in the presence of a 50-fold
      excess of nonlabeled native LDL, Ang II-LDL, Ac-LDL, or oxidized LDL (Ox-LDL).
      Whereas native LDL had no effect on the degradation of Ang II-125I-LDL by the
      macrophages, Ac-LDL, Ox-LDL, and Ang II-LDL reduced the cellular uptake of the
      lipoprotein by 77%, 82%, and 87%, respectively. Similarly, fucoidin but not free
      Ang II reduced macrophage degradation of the labeled Ang II-LDL. We conclude that
      Ang II can modify LDL to a form that is not oxidized or aggregated but is still
      taken up at an enhanced rate by macrophages via the scavenger receptor.

PMID- 8548434
TI  - Comminuted humeral head fractures: a multicenter analysis.
AB  - Three centers' experience with 93 comminuted humeral head fractures were
      clinically (Constant score) and radiologically (Neer) analyzed. The results
      revealed fundamental differences between the various types of fractures depending
      on the number of fragments. For three-part fractures open reduction and internal
      fixation (mean Constant scores 83 and 91 points, respectively) or conservative
      treatment (78 points) seem to be indicated. The prognosis for four-part fractures
      is determined largely by the vascular supply of the head fragment with a high
      risk of humeral head osteonecrosis. For this reason primary prosthetic
      replacement (mean Constant score, 74 points compared with 54 points for
      conservative treatment and 52 points for open reduction) should be recommended
      for this type of fracture. In conclusion, we stress the importance of fracture
      type directing the therapeutic modality.

PMID- 8548435
TI  - Shoulder function after displaced fractures of the proximal humerus.
AB  - It is difficult to predict the outcome of comminuted fractures of the proximal
      humerus and give guidelines for optimal treatment. Different treatment modalities
      are available, and there are various scoring systems for postoperative
      evaluation. The aim of this study was to assess the functional outcome after
      three- and four-part fractures of the humeral head in 38 patients, with a 3-year
      follow-up. Twenty-eight patients were treated conservatively, seven were operated
      on with open reduction and internal fixation, and three received a
      hemiarthroplasty. All patients were examined clinically and radiographically.
      Neer and Constant scoring systems were used. The functional outcome after three
      part fractures was generally good. Twenty-five of 26 patients with a three-part
      fracture could accept their shoulder situation. Range of motion was significantly
      lower in the four-part fracture group. Mean flexion was 89 degrees compared with
      120 degrees in the three-part fracture group. Necrosis of the humeral head was
      found in 2 cases, both four-part fractures. Osteoarthrosis developed in 13 cases
      (6 with a three-part fracture, 7 with a four-part fracture). No disability was
      found in 16 of 24 patients with three-part fractures, and in 4 of 11 patients
      with four-part fractures. There was strong agreement between the Constant score
      and the patients' opinions.

PMID- 8548436
TI  - Treatment of midshaft clavicular nonunion with plate fixation and autologous bone
      grafting.
AB  - We studied the results of 16 consecutive midshaft clavicular nonunions operated
      on at the Shoulder and Elbow Clinic during the period from 1990 to 1993. All
      patients were treated with rigid 3.5 mm plate fixation and autologous cancellous
      bone grafting. Union of the fractures was achieved in all except one case, with a
      reconstruction ratio (restoration of bone length) of 0.96 (range 0.88 to 1.03).
      At follow-up 12 of 16 patients had returned to their preinjury activity level and
      according to the Constant score had obtained an excellent result. Two patients
      were graded as good, one as fair, and one had a failure. Thirteen of 16 patients
      were satisfied with the cosmetic outcome, assessing their cosmetic result as
      either good or excellent. Rigid plate fixation and restoration of clavicular
      length with autologous cancellous bone graft is recommended for the treatment of
      symptomatic clavicular midshaft nonunions.

PMID- 8548437
TI  - Patient self-assessment of health status and function in glenohumeral
      degenerative joint disease.
AB  - One hundred three consecutive patients with primary glenohumeral degenerative
      joint disease completed standard questionnaires regarding their general health
      status (Short Form-36) and the function of their shoulder (Simple Shoulder Test).
      These patients' self-assessed health status indicated overall bodily pain,
      physical functioning, and physical role fulfillment scores that were
      significantly below those of population-based control groups. Self-assessed
      shoulder functions were likewise consistently below those of patients with normal
      shoulders. These deficits clearly indicated the problems that the patients
      desired to have resolved by treatment. The use of self-assessment questionnaires
      to routinely characterize patients with shoulder conditions is practical in the
      context of a busy practice. These data enable surgeons to understand the
      condition from the patient's perspective. This understanding should be central to
      the planning of treatment and to the evaluation of treatment effectiveness.

PMID- 8548438
TI  - Technique for selecting capsular tightness in repair of anterior-inferior
      shoulder instability.
AB  - Part I of our study consisted of sending a survey questionnaire to all members of
      the American Shoulder and Elbow Surgeons in which specific questions were asked
      about their technique of surgical repair in patients with anterior instability
      who had capsular laxity or injury in conjunction with marked inferior laxity.
      Part II is a description of the technique and preliminary results in 18 patients
      of a modified anterior-inferior capsular shift technique that tightens the
      inferior capsule with the shoulder positioned in abduction and external rotation
      and the superior capsule with the shoulder in adduction and external rotation. Of
      the members of the Society of the American Shoulder and Elbow Surgeons who
      responded to the survey, 80% agreed that preservation of external rotation was
      important and that shoulder position at the time of capsular repair might
      influence the ultimate range of motion obtained. However, no more than 50% of the
      respondents agreed on any one position for the arm when repairing the capsule.
      The most common responses for each position were flexion 0 degrees (49%) (range,
      0 degrees to 40 degrees), abduction 30 degrees (24%) (range, 0 degrees to 80
      degrees), and external rotation 30 degrees (37%) (range, 0 degrees to 70
      degrees). The average postoperative follow-up period for the 18 patients was 27
      months (range, 24 to 39 months). Of the 18 patients, 11 (61%) maintained
      symmetric motion; the others had minimal loss of external rotation compared with
      that of the contralateral shoulder. Six of eight patients with repair on the
      dominant side were able to return to full premorbid recreational throwing or
      racquet sports, and seven with repair on the nondominant side returned to full
      participation in overhead sports such as basketball and swimming. We conclude
      that this method of "selective" capsular repair may be a useful guideline to
      gauge the degree of capsular tightening in patients who have capsular injury or
      laxity.

PMID- 8548439
TI  - Factors influencing the results of a modified Bankart procedure.
AB  - Forty-two shoulders in 40 patients operated on for anterior instability between
      1986 and 1991 were reexamined. The mean follow-up was 47 months. The
      pathoanatomic findings at surgery were a Bankart lesion in 42 shoulders, a Hill
      Sachs lesion in 31 shoulders, and a rounded or defective anterior glenoid rim in
      29 shoulders. The surgical technique consisted of an open reinsertion of the
      anterior capsule-labral complex. Four shoulders had one or more recurrent
      anterior dislocations, and four shoulders had recurrent anterior subluxations.
      Three redislocations were caused by severe trauma. The presence and magnitude of
      a Hill-Sachs lesion did not influence the frequency of recurrence. An osseous
      defect of the glenoid rim > or = 3 mm was found in three patients, one of whom
      had redislocation after surgery. In patients with a large Bankart lesion the rate
      of recurrence was significantly higher.

PMID- 8548440
TI  - Anatomic variants of the coracoacromial ligament.
AB  - Cadaveric anatomic dissections of 50 shoulders have been done with measurement
      and histologic analysis of the coracoacromial ligament. In subjects older than 50
      years of age the coracoacromial ligament does not have a constant form. Three
      main types were identified: quadrangular, Y-shaped, and a broad band. A
      previously unreported type of coracoacromial ligament the multiple banded
      ligament, was found. It had the largest coracoid attachment. This ligament was
      similar to the Y form but with an additional band extending inferiorly and
      medially toward the base of the coracoid. Histologic analysis indicates the
      multiple banded type could be more common than this study suggests.

PMID- 8548441
TI  - Acromial structure and tears of the rotator cuff.
AB  - Rotator cuff lesions have been related to the structure of the acromion. We
      report a clinical review of 56 shoulders and the analysis of their acromial
      structure as seen on the radiographic arch (outlet) view and magnetic resonance
      imaging. The shoulders were classified as acromial type I (flat), type II
      (curved), or type III (hooked). On plain radiographs 89% of type III acromions
      had tearing of the rotator cuff (p < 0.001). The association between acromial
      type as determined on magnetic resonance imaging and the presence of rotator cuff
      tearing was less significant. Magnetic resonance imaging offered no additional
      benefit over plain radiographs for determining acromial type. In addition, a
      method of quantitating acromial structure (the "acromial angle") was devised.
      This angle showed a significant association with acromial types (p < 0.0001) seen
      on plain radiographs and had good interobserver reproducibility (coefficient of
      variation, 0.1). With this measurement system a type I acromion had an acromial
      angle of 0 degrees to 12 degrees; a type II acromion, 13 degrees to 27 degrees;
      and a type III acromion, greater than 27 degrees.

PMID- 8548442
TI  - Rotator cuff and posterior-superior glenoid labrum injury associated with
      increased glenohumeral motion: a new site of impingement.

PMID- 8548443
TI  - Disruption of the posterior-lateral shoulder capsule.

PMID- 8548444
TI  - Scapular fracture in a professional boxer.

PMID- 8548445
TI  - Fracture of the radial head with ulnar collateral ligament rupture.

PMID- 8548446
TI  - EF-hands reach out.

PMID- 8548448
TI  - The crystal structure of the antifungal protein zeamatin, a member of the
      thaumatin-like, PR-5 protein family.

PMID- 8548447
TI  - Structure of the multifunctional loops in the nonclassical ATP-binding fold of
      glutathione synthetase.

PMID- 8548449
TI  - Picture Story. Three's company.

PMID- 8548450
TI  - The structure of r(UUCGCG) has a 5'-UU-overhang exhibiting Hoogsteen-like trans
      U.U base pairs.
AB  - The crystal structure of the RNA fragment, 5'-r(UUCGCG)-3', has been determined
      at 1.4 A resolution by a combination of single isomorphous replacement and
      molecular search methods. The 3'-terminal CGCG portion of the hexamer engages in
      Watson-Crick hydrogen bonding while the 5'-terminal UU-overhang forms novel
      Hoogsteen-like U.U self-base pairs with the overhang of an adjacent duplex. The
      U.U pairs display a single conventional hydrogen bond between O4 (U1) and N3 (U8)
      and a CH-O hydrogen bond between C5-H (U1) and O4 (U8), through the Hoogsteen
      face of the pyrimidine base U1. This unusual arrangement of one of the bases
      results in a trans U.U pair on antiparallel strands in contrast to the usual cis
      base pairs. The structure emphasizes the pronounced polymorphism of U.U pairs and
      has implications for folding of RNA molecules.

PMID- 8548451
TI  - The bait in the Rubisco mousetrap.

PMID- 8548452
TI  - A novel form of the DNA double helix imposed on the TATA-box by the TATA-binding
      protein.
AB  - The structure of the TATA-box bound to the TATA-binding protein revealed a new
      and unexpected deformation of the double helix leading to a sharp change in the
      DNA trajectory. Here we show that the deformation imposed upon the TATA-box
      represents a novel form of the double helix--named TA-DNA--which differs from A
      DNA by a single conformational parameter, namely the rotation around the
      glycosidic bond. This rotation causes a 50 degrees inclination of the base pairs
      in the TATA-box which in turn results in abrupt change in the trajectory of the
      flanking B-DNA segments. The observation that the TATA sequence can assume an A
      DNA conformation coupled to the simplicity of the transition from A-DNA to TA-DNA
      may be the reason for the presence of the TATA sequence in a wide range of
      promoters.

PMID- 8548454
TI  - Stabilization of proteins by glycosylation examined by NMR analysis of a
      fucosylated proteinase inhibitor.
AB  - Here we investigate the effects of the naturally occurring threonine-linked L
      fucose moiety on the structure, dynamics and stability of the proteinase
      inhibitor PMP-C (Pars intercerebralis major peptide C). The three-dimensional
      structure of PMP-C fucosylated on Thr 9 has been determined by NMR spectroscopy
      and simulated annealing. The fucose ring is very well ordered, held in place by
      hydrophobic and hydrogen bond interactions with Thr 16 and Arg 18. Comparing the
      NMR data and the structure of the fucosylated inhibitor with those of the
      nonfucosylated form shows that conformational changes only occur in the vicinity
      of the fucose moiety. Nevertheless, a comparative analysis of the exchange rates
      of amide protons indicates that fucosylation is responsible for an overall
      decrease of the dynamic fluctuations of the molecule. This correlates well with
      an increase in stability of approximately 1 kcal mol-1 as monitored by thermal
      denaturation.

PMID- 8548455
TI  - Amino-acid substitutions in a surface turn modulate protein stability.
AB  - A surface turn position in a four-helix bundle protein, Rop, was selected to
      investigate the role of turns in protein structure and stability. Although all
      twenty amino acids can be substituted at this position to generate a correctly
      folded protein, they produce an unusually large range of thermodynamic
      stabilities. Moreover, the majority of substitutions give rise to proteins with
      enhanced thermal stability compared to that of the wild type. By introducing the
      same twenty mutations at this position, but in a simplified context, we were able
      to deconvolute intrinsic preferences from local environmental effects. The
      intrinsic preferences can be explained on the basis of preferred backbone
      dihedral angles, but local environmental context can significantly modify these
      effects.

PMID- 8548453
TI  - Design, biological activity and NMR-solution structure of a DNA analogue of yeast
      tRNA(Phe) anticodon domain.
AB  - Design of biologically active DNA analogues of the yeast tRNA(Phe) anticodon
      domain, tDNAPheAC, required the introduction of a d(m5C)-dependent, Mg(2+)
      induced structural transition and the d(m1G) disruption of an intra-loop dC.dG
      base pair. The modifications were introduced at residues corresponding to m5C-40
      and wybutosine-37 in tRNA(Phe). Modified tDNAPheAC inhibited translation by 50%
      at a tDNAPheAC:ribosome ratio of 8:1. The molecule's structure has been
      determined by NMR spectroscopy and restrained molecular dynamics with an overall
      r.m.s.d. of 2.8 A and 1.7 A in the stem, and is similar to the tRNA(Phe)
      anticodon domain in conformation and dimensions. The tDNAPheAC structure may
      provide a guide for the design of translation inhibitors as potential therapeutic
      agents.

PMID- 8548456
TI  - Mapping the structure of a non-native state of staphylococcal nuclease.
AB  - Non-native states of proteins populated at extremes of pH, or by mutation or
      truncation of the protein sequence, are thought to be equilibrium models for
      kinetic intermediates on the folding pathway. While the global physical
      properties of these molecules have been well characterized, analysis of their
      structure by NMR spectroscopy has proven difficult. Here we report the use of a
      new chemical cleavage technique, based on reactive oxygen species, to map the
      backbone fold of a truncated form of staphylococcal nuclease in a non-native
      state. The fragment adopts a native-like fold, however the technique also reveals
      regions of non-native structure.

PMID- 8548457
TI  - Structure of a novel extracellular Ca(2+)-binding module in BM-40.
AB  - The EF-hand is a highly conserved Ca(2+)-binding motif found in many cytosolic
      Ca(2+)-modulated proteins. Here we report the crystal structure at 2.0 A
      resolution of the carboxy-terminal domain of human BM-40 (SPARC, osteonectin), an
      extracellular matrix protein containing an EF-hand pair. The two EF-hands
      interact canonically but their detailed structures are unusual. In the first EF
      hand a one-residue insertion is accommodated by a cis-peptide bond and by
      substituting a carboxylate by a peptide carbonyl as a Ca2+ ligand. The second EF
      hand is stabilized by a disulphide bond. The EF-hand pair interacts tightly with
      an amphiphilic amino-terminal helix, reminiscent of target peptide binding by
      calmodulin. The present structure defines a novel protein module occurring in
      several other extracellular proteins.

PMID- 8548458
TI  - The crystal structure of GMP synthetase reveals a novel catalytic triad and is a
      structural paradigm for two enzyme families.
AB  - The crystal structure of GMP synthetase serves as a prototype for two families of
      metabolic enzymes. The Class I glutamine amidotransferase domain of GMP
      synthetase is found in related enzymes of the purine, pyrimidine, tryptophan,
      arginine, histidine and folic acid biosynthetic pathways. This domain includes a
      conserved Cys-His-Glu triad and is representative of a new family of enzymes that
      use a catalytic triad for enzymatic hydrolysis. The structure and conserved
      sequence fingerprint of the nucleotide-binding site in a second domain of GMP
      synthetase are common to a family of ATP pyrophosphatases, including NAD
      synthetase, asparagine synthetase and argininosuccinate synthetase.

PMID- 8548459
TI  - Tattle tales.

PMID- 8548460
TI  - A canonical structure for the ligand-binding domain of nuclear receptors.
AB  - The ability of nuclear receptors (NRs) to activate transcription of target genes
      requires the binding of cognate ligands to their ligand-binding domains (LBDs).
      Information provided by the three-dimensional structures of the unliganded RXR
      alpha and the liganded RAR gamma LBDs has been incorporated into a general
      alignment of the LBDs of all NRs. A twenty amino-acid region constitutes a NR
      specific signature and contains most of the conserved residues that stabilize the
      core of the canonical fold of NR LBDs. A common ligand-binding pocket, involving
      predominantly hydrophobic residues, is inferred by homology modelling of the
      human RXR alpha and glucocorticoid receptor ligand-binding sites according to the
      RAR gamma holo-LBD structure. Mutant studies support these models, as well as a
      general mechanism for ligand-induced activation deduced from the comparison of
      the transcriptionally active RAR gamma holo- and inactive RXR alpha apo-LBD
      structures.

PMID- 8548461
TI  - Structural transitions during activation and ligand binding in hexadecameric
      Rubisco inferred from the crystal structure of the activated unliganded spinach
      enzyme.
AB  - Activation of ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco; EC
      4.1.1.39) by CO2 involves carbamylation of Lys 201 and the subsequent binding of
      a magnesium ion to complete the active site. The refined crystal structure of
      activated Rubisco shows that the magnesium ligands are Asp 203, Glu 204, the
      carbamate of Lys 201, and three water molecules. Structural differences between
      the unactivated and activated forms are minimal. Substrate binding replaces water
      ligands around the metal and triggers substantial structural changes in loops
      covering the active site. This leads to a contraction and tightening of the
      structure of the large subunits with the movements transmitted to and modulated
      by the small subunits.

PMID- 8548462
TI  - Fluoroscopically guided percutaneous gastrostomy: current status.
AB  - The authors review the current status of fluoroscopically guided percutaneous
      gastrostomy (FGPG). The indications for this procedure have been expanded since
      the technique was first described over a decade ago. Ther are few
      contraindications to FGPG, although modifications are required in some
      situations. The procedure involves placing a feeding tube into the stomach by a
      modified Seldinger technique. According to the literature, most
      interventionalists do not routinely employ gastropexy. The insertion of
      gastrojejunostomy feeding tubes rather than gastrostomy feeding tubes to reduce
      gastroesophageal reflux remains controversial. Complications after FGPG are rare.
      Feeding tubes inserted in this manner allow satisfactory establishment and
      maintenance of enteral feeding. The technique compares favourably with other
      methods of inserting gastrostomy tubes.

PMID- 8548463
TI  - Left atrial myxoma presenting as Gerstmann syndrome.
AB  - The authors describe a 29-year-old woman who presented with Gerstmann syndrome
      secondary to underlying left atrial myxoma. The clinicoradiologic features of
      atrial myxoma, as well as its neurologic manifestations, are reviewed.

PMID- 8548464
TI  - Aortic arch interruption associated with ruptured cerebral aneurysm.
AB  - The authors present a case of aortic arch interruption in an adult, an anomaly
      that was discovered coincidentally during angiography for ruptured cerebral
      aneurysm. The presentation in adulthood with rupture of the aneurysm and the
      successful surgical treatment of both abnormalities are unusual.

PMID- 8548465
TI  - Nephrotoxicity of ioxaglate and ioversol assessed by glomerular filtration rate:
      a pilot study.
AB  - OBJECTIVE: To determine the effect of ioxaglate and ioversol on glomerular
      filtration rate (GFR) in a heterogeneous inpatient group to allow calculation of
      the necessary sample size for a randomized trial. PATIENTS AND METHODS: The study
      group consisted of 36 men and 12 women, ranging in age from 25 to 79 (mean 63)
      years. Fourteen of the patients, those undergoing abdominal aortography with or
      without renal arteriography, received ioxaglate (Hexabrix 320; 40 to 240 [mean
      141] mL), and the remaining 34, those receiving intravenous injections and those
      undergoing computed tomography with arterioportography or carotid arteriography,
      received ioversol (Optiray 320; 20 to 180 [mean 87] mL). GFR was measured by
      determining the clearance of diethyl-enetriaminepenta-acetic acid labelled with
      technetium-99m up to 72 hours before and 24 hours after administration of the
      contrast medium. Risk factors for nephrotoxicity included diabetes (7 patients)
      and pre-existing renal impairment (mild in 11 and severe in 6). RESULTS: GFR
      decreased by 20% to 34% in six patients (13%); in only one of these was the serum
      level of creatinine increased at 24 hours. One of these six patients had received
      120 mL of ioversol for carotid arteriography and had no risk factors for
      nephrotoxicity. The other five had received 40 to 187 (mean 115) mL of ioxaglate,
      three for abdominal aortography and two for selective renal arteriography. The
      risk factors in these patients included diabetes (two patients) and severe pre
      existing renal impairment (two patients). Renal failure necessitating treatment
      did not develop in any of the patients. CONCLUSIONS: A decrease in GFR occurred
      more often with ioxaglate than with ioversol and usually occurred in patients
      with additional risk factors. Injection of contrast medium into the abdominal
      aorta or the renal artery may increase the risk of nephrotoxicity. Changes in
      serum level of creatinine at 24 hours were not reliable in identifying patients
      with decreased GFR. On the basis of these data, the authors estimate that a group
      of 194 patients would be necessary for a randomized trial comparing the
      nephrotoxicity of ioxaglate and ioversol for abdominal aortography.

PMID- 8548466
TI  - Misdiagnosis of renal cell carcinoma by computed tomography with angiography: a
      potential pitfall.
AB  - The introduction of helical computed tomography (CT) has led to an increase in
      the number and complexity of CT protocols. This situation has resulted in a new
      source of error in the interpretation of CT scans. The authors report a case in
      which a hyperattenuating cyst discovered incidentally at the time of CT with
      angiography could have been misdiagnosed as renal cell carcinoma.

PMID- 8548467
TI  - Osteosarcoma in a 19-month-old girl.
AB  - Osteosarcoma develops only rarely in patients under 6 years of age. The authors
      describe a 19-month-old girl who presented with proximal humeral metaphyseal
      osteosarcoma. To the authors' knowledge, this report represents the youngest
      patient with this bone lesion.

PMID- 8548468
TI  - Magnetic resonance imaging and histopathologic appearances of benign soft-tissue
      masses of the foot.
AB  - Magnetic resonance imaging (MRI) is now the modality of choice for the
      investigation of soft-tissue tumours, providing excellent anatomic detail and
      soft-tissue contrast. As the availability of MRI has increased, the number of
      requests for studies of the foot and ankle has similarly increased. The imaging
      department at the authors' institution, a tertiary care teaching hospital, has a
      large orthopedic and podiatric referral base, and as a consequence the authors
      have had the opportunity to study a large variety of benign soft-tissue tumours
      with MRI. In this pictorial essay they review the MRI and pathological
      appearances of the most common benign soft-tissue tumours that occur in the foot
      and ankle.

PMID- 8548469
TI  - Kinematic magnetic resonance imaging of the normal shoulder: assessment of the
      labrum and capsule.
AB  - OBJECTIVE: To examine the normal shoulder, specifically the labrum and the
      capsule, with kinematic magnetic resonance imaging (MRI) in asymptomatic
      volunteers. SUBJECTS AND METHODS: Fourteen asymptomatic volunteers 22 to 53 years
      of age were studied with a 1.5-T Signa Advantage imager (GE Medical Systems,
      Milwaukee). Successive static gradient-echo images were obtained in the
      transverse plane at the mid-glenoid level as the shoulder was successively
      positioned from full internal to full external rotation. These images were
      correlated with standard transverse T1-weighted spin-echo images and gradient
      echo volume images obtained in the neutral position. RESULTS: The anterior labrum
      was slightly mobile during rotation in 11 subjects and changed shape from blunted
      or round to triangular in 8 subjects. A wide variation in morphologic features of
      the anterior labrum was observed. During rotation, a slight increase in signal
      intensity was noted in the anterior labrum of five of the subjects. The posterior
      labrum maintained a relatively stable triangular shape in most cases. Dynamic
      study allowed assessment of the anterior capsule insertion in all cases. Three
      subjects had type 1 and 11 had type 2 capsular insertion. No cases of type 3
      insertion were identified. CONCLUSIONS: Variation in the shape and signal
      intensity of the anterior labrum observed in normal asymptomatic volunteers
      during transverse kinematic examination of the shoulder should be taken into
      account during evaluation of shoulder instability, since this variation may be
      clinically insignificant. Kinematic MRI allows easy evaluation of the anterior
      capsule.

PMID- 8548470
TI  - Spinal angiolipoma mimicking extradural lipomatosis.
AB  - Spinal angiolipoma is a rare, benign tumour. More than 90% of cases arise
      extradurally. The authors report an extradural spinal angiolipoma in a 54-year
      old man. Conventional T1-weighted and T2-weighted magnetic resonance imaging
      (MRI) demonstrated an excessive amount of extradural adipose tissue posteriorly,
      extending from the level of the third to the ninth thoracic vertebra. The signal
      intensity within the spinal cord was normal. These findings were initially
      misinterpreted as being of little clinical significance. When the patient's
      condition deteriorated, myelography was performed, and extradural compression of
      the thecal sac was demonstrated. At surgery spinal angiolipoma was confirmed. The
      ease with which the MRI features of this lesion can be overlooked, as well as
      imaging strategies to avoid this pitfall, are discussed.

PMID- 8548471
TI  - Helical computed tomography at 1.5:1 pitch reconstructed at 15-mm and 7-mm
      intervals for examination of patients with suspected metastatic disease.
AB  - OBJECTIVE: To document the need for overlapped reconstruction when using helical
      computed tomography (CT) software that reconstructs 10-mm-collimation, 1.5:1
      pitch images at 15-mm intervals in follow-up examination of patients with
      suspected metastatic disease. PATIENTS AND METHODS: Forty consecutive patients
      with known or suspected metastatic disease were examined with helical CT at 10-mm
      collimation and 1.5:1 pitch. The studies were examinations of the chest, abdomen
      and pelvis; the chest and abdomen; or the abdomen and pelvis. Two image sets, one
      prospectively reconstructed at 15-mm intervals and the other retrospectively
      reconstructed at 7-mm intervals, were independently reviewed by three
      radiologists, and the number, size and location of lesions were documented.
      Differences in interpretation were resolved by consensus. The lesions detected on
      the two sets of images were classified according to lesion size and location, and
      the results were analysed by multivariate analysis of variance with repeated
      measures. RESULTS: Images reconstructed at 7-mm intervals revealed a total of 436
      lesions, 127 (41%) more than were revealed by images reconstructed at 15-mm
      intervals. The number of lesions less than 1 cm in diameter that were visible in
      the two sets of images was significantly different (p = 0.018). However, there
      was no significant difference between the two sets of images in terms of lesion
      location. CONCLUSION: Metastatic lesions may be missed by helical CT at 1.5:1
      pitch if overlapped reconstruction is not performed.

PMID- 8548472
TI  - Residents' corner. Answer to case of the month #35. Bilateral subependymal giant
      cell astrocytoma associated with tuberous sclerosis.

PMID- 8548474
TI  - Effects of the cholecystokinin receptor antagonist L-364,718 on pancreatitis
      induced by a deficient in choline and supplemented with ethionine (CDE) diet in
      the rat.
AB  - The role of cholecystokinin (CCK) in the development of a necrotizing acute
      pancreatitis induced by a diet deficient in choline and supplemented with
      ethionine (CDE) has been evaluated in the rat by using a potent CCK receptor
      antagonist L-364,718. Acute pancreatitis was induced by administration of CDE
      diet for 14 days. L-364,718 administration was carried out by subcutaneous
      injections at dose of 0.1 mg/kg/day. Pancreatic exocrine secretion (flow,
      protein, amylase and trypsin outputs) in resting and under infusion of 1.25
      microgram/kg/h of CCK-8 were used to evaluate the pancreatic functionality.
      Others parameters (serum amylase, percentage fluid in pancreas, haematocrit and
      mortality) evaluated the severity of pancreatitis. L-364,718 slightly reduced the
      mortality and the increases of percentage of fluid accumulated in pancreas in CDE
      diet acute pancreatitis. Basal and CCK stimulated pancreatic secretion was
      significantly depressed 36 hours after L-364,718 treatment. A slight response to
      CCK was observed. Nevertheless it was lower than usually observed in control
      rats. Our results demonstrate that in the rat, chronic L-364,718 treatment did
      not completely restore pancreatic activity in acute pancreatitis induced by CDE
      diet. Hence CCK cannot be considered as the main factor involved in the
      development of this pancreatitis model.

PMID- 8548473
TI  - Perfusion of gills isolated from the hyper-hyporegulating crab Pachygrapsus
      marmoratus (Crustacea, Decapoda): adaptation of a method.
AB  - This paper reports the adaptation of a branchial perfusion technique to the gills
      of the small hyper-hyporegulating crab, Pachygrapsus marmoratus. The
      physiological quality of the preparation has been established and preliminary
      measurements of the transepithelial potential difference (PD) and sodium fluxes
      were reported. A clear-cut distinction has to be made between anterior and
      posterior gills. With symmetrical bathing conditions (same saline on both sides
      of the epithelium), a significant transepithelial PD was measured only in
      posterior gills isolated from crabs acclimated to dilute sea water. This
      hemolymph-side negative PD is shown to require biological energy and to be
      sensitive to ouabain. Na+ influx was larger than efflux, indicating the
      occurrence of a net inward of Na+. The active nature of the Na+ influx was
      established.

PMID- 8548476
TI  - Systemic baroreflex alterations in prehepatic portal hypertensive conscious rats.
AB  - In portal hypertensive patients and experimental models, hyperdynamic circulatory
      disturbances associated to a reduced peripheral resistance and an increased
      cardiac output appeared. The aim of this research is the study of the baroreflex
      system behavior partially portal vein ligated-portal hypertensive rats. Sham
      operated rats (S) (n = 7) and portal hypertensive rats (PH) (n = 9) were used. In
      anesthetized rats, catheters were introduced into a jugular vein for drug
      injection and into the ventral tail artery to record blood pressure and heart
      rate. When rats were conscious and moving freely, a bolus injection of
      phenylephrine hydrochloride (6 micrograms/kg) was injected in the vein. A sigmoid
      curve relating systolic blood pressure and heart period was dressed. We analyzed:
      1) The gain or sensitivity: the slope of the regression line; 2) The threshold:
      systolic blood pressure at which the regression begins to be linear. The results
      were: mean arterial pressure (mmHg): S = 103 +/- 7; PH = 109 +/- 3; gain
      (ms/mmHg): S = 1.29 +/- 0.10; PH = 0.62 +/- 0.04 (p < 0.001); threshold (mmHg): S
      = 145 +/- 7; PH = 146 +/- 4. The baroreceptor reflex sensitivity was
      significantly decreased. No differences appeared in the mean arterial pressure
      and in the reflex threshold. It is suggested that portal hypertension induces
      alterations in baroreflex regulation of arterial blood pressure.

PMID- 8548475
TI  - Effect of catecholestrogens on [3H]-GABA uptake by hypothalamic crude
      synaptosomes.
AB  - Catecholestrogens (CE), 2-hydroxyestradiol, 2-hydroxyestrone and primary
      estrogens, estradiol and estrone were tested in their ability to compete for the
      high affinity uptake of [3H]-GABA into crude synaptosomal fractions. Aliquots of
      the crude synaptosomal fraction obtained from normal rats were incubated for 10
      min at 37 degrees C with [3H]-GABA in the presence, or absence, of estrogens and
      catecholestrogens. Neither estradiol nor estrone modified the specific [3H]-GABA
      uptake into crude synaptosomal fractions. On the contrary, CE significantly
      affected the specific [3H]-GABA uptake in a dose-dependent manner: low
      concentrations of CE enhanced the uptake; this effect disappeared with high
      concentrations of the compounds. The stimulatory effect of CE on [3H]-GABA uptake
      was blocked when samples were coincubated with nipecotic acid, thus suggesting
      that this effect is specific rather than the result of non-specific interactions
      of CE with the hypothalamic membrane.

PMID- 8548477
TI  - Receptor-mediated induction of human glomerular epithelial cell alkaline
      phosphodiesterase I by glucocorticoids.
AB  - Alkaline phosphodiesterase I was demonstrated in human glomerular mesangial cells
      (HGEC) as an ectoenzyme. Treatment of HGEC by dexamethasone increased surface
      phosphodiesterase I activity in a dose- and time-dependent manner. Maximal
      increase of phosphodiesterase I activity, about twice, occurred after treatment
      with 5 microM dexamethasone for 6 days. Cycloheximide prevented and RU 38486, a
      glucocorticoid receptor antagonist, suppressed the dexamethasone induced increase
      in phosphodiesterase I activity. This study shows that HGEC have a surface
      phosphodiesterase I controlled by glucocorticoids through a receptor-mediated
      mechanism.

PMID- 8548478
TI  - Non-invasive electrogastrography. Part 1: Correlation between the gastric
      electrical activity in dogs with implanted and cutaneous electrodes.
AB  - Experiments were made on dogs with bipolar silver ball-shaped electrodes
      chronically implanted on the muscle wall of the stomach. The electrical activity
      of the gastric muscle wall (electrogastromyogram-EGMG) was characterized by slow
      potential changes during the quiescent period of the migrating myoelectric
      complex (MMC) and bursts of spike potentials during the activity period of MMC.
      Cutaneous (surface) electrodes were placed on the abdominal wall. Waves with a
      rhythm of 4.5-5 cpm were led off by the cutaneous electrodes (electrogastrogram
      EGG), simultaneously with the EGMg. The bursts of spike potentials with the slow
      gastric potentials in the EGMG corresponded to an increase of the amplitude of
      the waves in the EGG. Good correlation was found between the number and frequency
      of spike potentials in a group and the wave amplitude in the EGG. EGG recorded on
      an electrogastrograph designed by us was characterized by low-amplitude waves
      corresponding to the slow waves during the period of quiescence of MMC and high
      amplitude waves corresponding to the bursts of spike potentials during the
      activity period of MMC. Therefore it is possible to determine the MMC of the
      stomach by the changes in the amplitude of the waves in the EGG.

PMID- 8548479
TI  - Non-invasive electrogastrography. Part 2. Human electrogastrogram.
AB  - The electrical activity of human stomach muscle wall-electrogastrogram (EGG), was
      led off by surface (cutaneous) electrodes placed on the abdominal wall and
      recorded on an electrogastrograph. A method for complete elimination of the
      cardiac artefact was elaborated and successfully implemented. It consists of a
      preliminary elimination of the QRS complex, based on its higher amplitude and
      slope. The eliminated intervals were replaced by linear segments. A subsequent
      low-pass filtering allowed to obtain a high quality EGG signal. The electrical
      activity of the stomach of healthy volunteers was characterized by waves with a
      frequency of 3.35 +/- 0.09 cpm during the quiescent periods and 2.99 +/- 0.14 cpm
      during the activity periods of the migrating myoelectrical complex (MMC). Bearing
      in mind the correlation between the bursts of spike potentials with the slow
      waves in the dog EGMG and the high-amplitude waves, characterizing the periods of
      activity in the dog EGG, we can better differentiate the periods of quiescence
      and activity by the amplitude of the waves. The wave amplitude during periods of
      quiescence was 81.13 +/- 20.61 microV, significantly different from the wave
      amplitude during periods of activity being 164.74 +/- 43.34 microV (n = 7). Thus
      with this method in visual inspection it is possible to identify MMC of the human
      stomach by the changes in the amplitude of the waves in the EGG.

PMID- 8548480
TI  - Liver microsomal phospholipid fatty acids behavior and its relationship to
      bilirubin UDP-glucuronyltransferase activity in bile duct ligated rats.
AB  - Phospholipid fatty acid composition and bilirubin UDP-glucuronyltransferase
      activity from liver microsomal membrane were studied in normal and in bile duct
      ligated rats. Incubation of normal microsomes with 15 microM bilirubin
      (considered as physiological concentration) yielded 60% bilirubin diglucuronide;
      in 2 days post-cholestatic rats, they showed 20% bilirubin diglucuronide which
      was undetectable in 8 days post-cholestatic group. When compared to controls,
      after 2 days of cholestasis, microsomal phospholipids showed a clear decrease in
      linoleic and arachidonic acids and an increment in palmitic and stearic acids. 8
      days post-cholestatic rats presented a marked increase in palmitic, oleic and
      docosaexaenoic acids, while linoleic and arachidonic acids decreased. Cholestasis
      produced disturbances in microsomal phospholipids fatty acid composition; but
      these changes are unable to explain entirely the severe damage observed in
      bilirubin diglucuronide formation.

PMID- 8548481
TI  - Inhibition of endothelium-derived relaxing factor in A6 cells.
AB  - The effects of endothelium-derived relaxing factor (EDRF) on Na+ transport in
      distal renal tubular A6 cells have been studied by inhibition of its synthesis
      with L-NAME (10(-2) mol/l). Na+ transport was monitored by measuring short
      circuit current, cell voltage, transepithelial, apical and basolateral membrane
      conductances. EDRF production in A6 cells was tested by application of its
      substrate L-arginine. The blockade of EDRF decreased significantly the Na+
      current (11 %), membrane potential (5 mV) and basolateral conductance (33 %), but
      did not affect the apical membrane conductance. Activation of apical Na+
      conductance by dexamethasone incubation (10(-7) mol/l) did not further influence
      the drop in Na+ current. The involvement of basolateral K+ channels in cell
      depolarization and in the reduction of basolateral conductance was tested in
      tissues with elevated basolateral K+/Cl- conductance ratios (by increasing bath
      osmolarity) and by application of barium (0.5-10(-3) mol/l) a K+ channel blocker.
      The results showed that the effect of L-NAME on the short-circuit current was
      more pronounced in A6 cells with increased K+/Cl- conductance ratios, but was
      almost nullified by barium. Finally, L-arginine fully restored the Na+ current,
      thus reversing the inhibition induced by L-NAME. We conclude that EDRF is basally
      released in A6 cells. Inhibition of EDRF by L-NAME directly interferes with Na+
      reabsorption. Since apical membrane conductance remains unchanged, the decrease
      in short-circuit current results from cell depolarization. The latter, together
      with the drop in basolateral conductance, might reflect inactivation of K+
      channels.

PMID- 8548482
TI  - [Involvement of urodilatin in the hydro-electrolytic modifications induced in man
      by a 6 degree head-down tilt].
AB  - On 6 healthy men, we measured: 1/ the effects of 28-day -6 degrees head-down tilt
      on the excretion of urodilatin and 2/ the relationship between urodilatin and
      urinary fluid, or sodium excretion. Aliquots of the pooled 24-h urine output were
      used. Urodilatin increased parallel to urinary fluid or Na+ at first day of head
      down tilt. Positive and statistically significant linear correlations could be
      established between urodilatin (and ANP) and urinary volume, or Na+ in five
      subjects on six. Urodilatin might participate as one of the several mechanisms of
      diuresis and natriuresis of first hours of head-down tilt.

PMID- 8548483
TI  - Sex and gonadal activity modify the effect of 2-hydroxyestradiol on hypothalamic
      GABA uptake in the rat.
AB  - The aim of this study was to determine the changes induced by sex and sexual
      steroids on the effect of the catecholestrogen 2-hydroxyestradiol (2OHE2) upon
      hypothalamic GABA uptake. For this purpose we have measured [3H]-GABA uptake by
      crude synaptosomal fractions obtained from normal female and male rats and from
      ovariectomized and virilized female rats in the presence or absence of increasing
      concentrations (0.1 to 100 microM) of 20HE2. The results presented in this paper
      demonstrate that the effect of the catecholestrogen varied according to sex: it
      potentiated the specific [3H]-GABA uptake in female rats, whereas it clearly
      inhibited the uptake in male and virilized rats. The enhancing effect of the
      catecholestrogen was not affected by ovariectomy, but a higher specific GABA
      uptake was observed in the ovariectomized animals. The present study provides the
      first evidence that the effect of 2OHE2 on hypothalamic GABA uptake depends on
      sex, thus suggesting the existence of a sexual dimorphism. Further studies in
      this field are required to elucidate the physiological significance and the
      underlying mechanism of the mentioned effect.

PMID- 8548484
TI  - Effect of glomerular cells interaction with macrophages on surface 5'
      nucleotidase activity.
AB  - Interaction of cultured rat mesangial cells with macrophages induces a marked
      increase in surface 5'-nucleotidase activity of these mesangial cells. A
      significant increase in surface 5'-nucleotidase was also observed upon
      interaction of rat fibroblast with macrophages, both in cocultures and after
      treatment of fibroblasts with macrophage conditioned medium. Interaction of
      glomerular epithelial cells in primary culture with macrophages had no effect on
      surface 5'-nucleotidase activity. No significant effect on enzyme activity was
      observed after interaction of mesangial-epithelial cells, mesangial cells
      fibroblasts, and epithelial cells-fibroblasts.

PMID- 8548485
TI  - Effects of ions substitutions and of inhibitors on transepithelial potential
      difference and sodium fluxes in perfused gills of the crab Pachygrapsus
      marmoratus.
AB  - With the same saline on both sides of the epithelium, a spontaneous inside
      negative transepithelial potential difference (PD) was measured in perfused
      posterior gills of the euryhaline crab Pachygrapsus marmoratus acclimated to
      dilute sea water. The origin of the PD and the transport properties of the
      epithelium were investigated by ionic substitutions and by application of
      inhibitors. Diffusion of Na+ and Cl- ions at the apical side contributes to the
      establishment of the PD. Sodium cyanide (10(-2) M) added to the perfusion and
      incubation media almost completely inhibited the transepithelial PD and
      considerably decreased the Na+ influx. Internally perfused ouabain (5.10(-3) M)
      halved the PD and the Na+ influx but had no effect on the Na+ efflux. Externally
      applied amiloride (10(-3) M) also reduced the Na+ influx by 27%. All inhibitions
      were concentration-dependent. From these results, it has been concluded that the
      transepithelial PD and Na+ influx are, at least partly, generated by active,
      metabolic energy-requiring processes. The effect of ouabain supports the
      existence of a Na+/K+ exchange mechanism linked to the presence of Na(+)-K+
      ATPase in the basolateral membrane of posterior gills. The effect of amiloride is
      discussed.

PMID- 8548486
TI  - Thermolytic salivation, substance P and kinins in rats.
AB  - In the heat, rats produce a large flow of saliva that they spread on their fur.
      We have tested whether substance P (SP) is involved in this response by using RP
      67580, a NK1 tachykinin receptor antagonist, in normal and in kininogen-deficient
      rats. In anaesthetized rats, the sialogogic effect of SP (1 and 5 micrograms.kg-1
      iv) was inhibited by RP 67580 (50 to 2500 micrograms.kg-1 iv). SP (5
      micrograms.kg-1 iv) did not modify the vascular permeability to 125I-labelled
      albumin in submaxillary glands but increased this permeability in periglandular
      soft tissues and in the ears. This effect was suppressed by RP 67580 (50 to 2500
      micrograms.kg-1 ip). Unanaesthetized normal male Wistar rats were exposed to
      ambient temperatures of 26 degrees C (thermoneutral range) or 36 degrees C for
      one hour. After this time period, a loss of body weight was observed. The
      thermolytic water loss reached 2% of body weight. This body weight loss was
      reduced by atropine (3 mg.kg-1 ip) or RP 67580 (50 to 2500 micrograms.kg-1 ip).
      The submaxillary glands were swollen and accumulated labelled albumin. This
      accumulation was reduced by atropine but was not affected by RP 67580. An
      extravasation of labelled albumin occurred in periglandular tissues. This
      accumulation was not modified by atropine which induced a large oedema of the
      soft tissues. Protein extravasation was suppressed by RP 67580 (2500
      micrograms.kg-1) which did not modify or increased the volume of the
      oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8548487
TI  - Determination by enhanced luminescence technique of liver antioxidant capacity.
AB  - A simple approach to quantitative determination of antioxidant capacity of rat
      liver homogenate is proposed. It consists of measuring chemiluminescence
      generated by a suitable system "detector" for .OH radicals produced from sodium
      perborate. The system generating the light signal contained luminol and compounds
      producing enhancement of light emission, such as sodium benzoate and indophenol.
      Two different methods, utilizing the same technique of enhanced luminescence,
      were set up. In a previous work, a parameter b, contained in the equation, which
      best describes the dependence of the intensity of light emission (E) on liver
      homogenate concentration (C) (E = a.C/exp(b.C), was found to be related to the
      level of antioxidants in the homogenate. Therefore, in the first method, the
      light emission from several dilutions of both liver homogenates, and homogenate
      and antioxidant mixtures, stressed with sodium perborate, was detected by a
      luminometer. The best fitting of data to theoretical equation provided b values,
      which were introduced in a system of equations relating such values to the
      antioxidant concentration. The solution of above system supplied the antioxidant
      concentration in the homogenate in terms of the equivalent concentration of the
      antioxidant used. In the other method, evaluations of the antioxidant capacity of
      liver homogenates were obtained by the determination of the ability of 10%
      homogenates to quench the light emission induced by either peroxidase or
      cytochrome c in comparison to the ability of antioxidant solutions. Both methods
      are able to evidence the decrease of the antioxidant concentration of liver
      homogenates after oxidative stress with ter-butylhydroperoxide. The value of both
      concentration changes and standard errors indicates that the method using a
      standard curve obtained with peroxidase, such as catalyst of radical reaction,
      and deferoxamine, such as antioxidant, is to be preferred.

PMID- 8548488
TI  - Na+ and Cl- net absorption by the isolated skin of Rana esculenta.
AB  - In the last five years, several measurements of 22Na+ influx (Ji) and outflux
      (Jo) across symmetrical parts of the isolated skin of Rana esculenta, under
      permanent short circuitation, were performed in our Institute. The mean value of
      the 22Na+ net fluxes (Ji-Jo) exceeded the mean value of the short circuit current
      measurements (1.14 +/- 0.04 versus 0.98 +/- 0.02 microE.cm-2.h-1, 253
      experiments). Since this discrepancy could be due to a concomitant Cl- net
      absorption, 36Cl- unidirectional fluxes were detected under similar experimental
      conditions. The Cl- net flux mean value was 0.11 +/- 0.02 microE.cm-2.h-1 (316
      experiments) which accounts for 70% of the discrepancy between the Na+ net flux
      and short circuit current. This Cl- net absorption occurred in the absence of
      electrochemical gradients and was very likely maintained by a Na+/K+/2Cl-
      cotransport located at the outermost membrane of the epithelium. In fact
      bumetanide challenge (10(-5) M in the external fluid) strongly inhibited 36Cl-
      influx and 22Na+ influx across this tissue and cleared off the discrepancy
      between short circuit current and sodium net flux.

PMID- 8548489
TI  - Emotional response and corticoadrenal function in anterodorsal thalami nuclei
      lesioned rats.
AB  - In male and female rats, the effect of limbic anterodorsal thalami nuclei lesions
      (ADTN) on the emotional reactivity and their relationship with corticoadrenal
      function were studied. The emotional reactivity was evaluated by means of the
      open-field test and the corticoadrenal function by means of plasma anol adrenal
      corticosterone concentration. The results demonstrate that, on the 8th or 9th day
      after the lesion, the male rats show lack of habituation and the female ones, an
      increase in emotional reactivity. They also indicate that the lesion of ADTN does
      not affect the corticoadrenal response to exposure to novel situations.

PMID- 8548490
TI  - [Analysis of iodine compounds in young rat skin in the period of suckling and in
      the adult. Effect of perchlorate].
AB  - In the suckling and adult rats equilibrated or no by 125I, cutaneous iodine
      analysed by dialysis and chromatography techniques (Dowex and Sephadex) was the
      purpose of this study. Dialysis studies had shown that most of steady or labelled
      skin iodine had an iodide form (90 to 95% of the total iodine). There were at
      least two intracellular iodide pools: the first one was quickly dialysable, in
      fact about 60 percent of initial radioactivity represented the intracellular
      iodide equilibrated with extracellular fluid. The other one wasn't or was little
      dialysable representing probably the cutaneous iodide storage compartment.
      Chromatography studies (Dowex or Sephadex) demonstrated that the skin of the
      young and adult rat contained T4 and T3 hormones in a small percentage. The
      iodide represented a value more than 90% of initial total radioactivity. Results
      concerning kinetic skin iodine, eight and twenty four hours after LT4(125)I
      injected to adults and to control and iodine deficient ten day old rats,
      confirmed those obtained here by Dowex chromatography and previous ones.
      Triiodothyronine (T3) might have an origin either in thyroid synthesis or in
      deiodination of T4. Consequently we may say that the skin of the 10 day and 14
      day old rats presented a great accumulation of iodide. The perchlorate inhibited
      this storage. Indeed, in young deficient iodine rats at birth, cutaneous iodide
      concentrations were reduced whereas those of T4 and T3 as well as the ratio T3/T4
      haven't been modified. Therefore the iodine deficiency seemed to have a few
      effects on the skin deiodinating activity. Indeed the skin of iodine deficient
      immature rat became unable to accumulate iodide. The main effect of the skin
      iodine deficiency was the inhibition of iodide transport from the extracellular
      fluid to the intracellular one, but not inside cellular structures.

PMID- 8548491
TI  - The regulation of liver protein degradation by aminoacids in vivo. Effects of
      glutamine and leucine.
AB  - The effects in vivo of the two major in vitro regulatory aminoacids, leucine and
      glutamine, on liver protein degradation were explored in male young adult Sprague
      Dawley rats. Protein degradation was stimulated by the injection of the
      antilipolytic drug 3,5 dimethylpyrazole (DMP), which rises glucagon and lowers
      insulin plasma levels. At the appropriate time-points (20 and 40 min) after the
      injection of DMP, glutamine or leucine (12.5 mg/kg b.w.) were injected
      intraperitoneally. The rate of liver protein breakdown was evaluated 60 min after
      the injection of DMP on the basis of the release of valine into the perfusate
      during a short term single pass liver perfusion. The aminoacid was assayed by an
      HPLC procedure. Results show that the administration of glutamine inhibited the
      DMP-induced increase in the rate of valine release from the perfused liver
      whereas the administration of leucine did not; neither of the aminoacids appeared
      to have any effect on the metabolic or endocrine changes that are required for
      the induction of liver autophagy and protein breakdown by DMP. It is concluded
      that the aminoacid glutamine has a powerful action on the in vivo regulation of
      liver protein breakdown, which is not apparent with leucine.

PMID- 8548493
TI  - Dietary intakes of energy and water-soluble vitamins in different categories of
      aging.
AB  - The dietary intakes of energy and the vitamins thiamin, riboflavin, B6, and C
      were assessed in four groups of elderly people, using the same modified dietary
      history method. The groups consisted of female nursing home residents (n = 40),
      people at admission to a nursing home (n = 21), free-living elderly people with a
      sedentary life style (n = 120), and physically active free-living elderly people
      (n = 66). Mean energy intake varied from 6.5 +/- 1.2 Megajoule (MJ)/day (nursing
      home residents) to 8.8 +/- 2.2 MJ/day (physically very active persons) in females
      and from 8.8 +/- 2.5 MJ/day (admission to nursing home) to 10.1 +/- 2.3 MJ/day
      (physically very active persons) in males. Dietary intakes of the selected
      vitamins were below the minimum requirements in almost half of the nursing home
      residents. However, the relative contribution of the various food groups to the
      dietary intake of these vitamins was similar in the four groups of elderly
      people. Stimulation of physical activity to increase energy requirements and use
      of foods with a high nutrient density may result in an improvement of dietary
      adequacy.

PMID- 8548494
TI  - Prior instrumental conditioning improves spatial cognition and attenuates changes
      in hippocampal function in aged rats.
AB  - These experiments examined the effects of long-term instrumental training on
      subsequent radial arm maze performance and synaptic transmission within the
      hippocampal formation. In the first experiment, young (3 mo) and aged (18 mo)
      male rats underwent 12 weeks of appetitive instrumental conditioning; half were
      continually reinforced and the other half alternated between reinforcement and
      extinction. Afterward, spatial cognition was evaluated using an eight-arm radial
      maze. Subjects undergoing instrumental training performed at rates superior to
      untrained (control) animals regardless of age or training condition; age-related
      differences did not exist in the trained groups. In the second experiment,
      subjects underwent 12 weeks of instrumental training with continuous
      reinforcement, and excitability of the hippocampus was examined by paired-impulse
      stimulation of the perforant path. Training enhanced maximal facilitation of
      population spikes evoked in the granule cell layer of the dentate gyrus of aged
      subjects to the degree that no statistical difference existed between young and
      aged animals. Data from untrained control animals indicated a robust decline in
      paired-impulse excitability in aged subjects. These findings suggest that
      learning-induced plasticity may attenuate both behavioral and neurobiological
      changes observed in aged subjects. It is postulated that disuse may underlie some
      of the cognitive changes exhibited across the life span.

PMID- 8548492
TI  - Hypothyroidism affects pulsatile LH secretion in pubertal orchiectomized rats.
AB  - The present study evaluated the effect of hypothyroidism on the pituitary
      testicular axis in rats rendered hypothyroid on the beginning of puberty. Rats
      were treated with propylthiouracil for 8 weeks and killed for determination of
      hormonal status and body parameters. For determination of pulsatile LH secretion
      other animals were orchiectomized two weeks before sampling. Analysis of the
      results led us to conclude that although the absolute weight of sex organs tended
      to decrease in hypothyroid animals, the relative weights were equal or higher
      than control, suggesting that the development of these organs were not affected
      by hypothyroidism; the androgenic activity of hypothyroid rat testes were
      preserved; basal plasma levels of pituitary hormones were similar in control and
      hypothyroid groups; the pulsatile LH secretion showed a decrease in the number of
      pulses, nadir mean and total LH secretion in hypothyroid animals. Our results
      demonstrate that although hypothalamic-pituitary axis of hypothyroid pubertal
      rats displays an abnormal pulsation LH release, no evidences of abnormalities in
      the reproductive system functions were found.

PMID- 8548495
TI  - Bilateral and unilateral neuromuscular function and muscle cross-sectional area
      in middle-aged and elderly men and women.
AB  - Forty-eight healthy men (M) and women (W), divided into two different age groups,
      i.e., M50 yrs (range 44-57; n = 12), W50 yrs (range 43-57; n = 12), M70 yrs
      (range 59-75; n = 12), and W70 yrs (range 62-75; n = 12), volunteered as subjects
      for examination of muscle cross-sectional area (CSA), maximal voluntary forces,
      force-time curves, and electromyographic activity of the knee extensor muscles
      during bilateral and unilateral isometric contractions. The maximal bilateral
      knee extension force and the average CSA values in M50 were greater (p < .05)
      than in M70 and in W50 were greater (p < .05-.001) than those recorded for W70.
      The early forces in the force-time curve were greater (p < .05) for M50 than for
      M70 and in W50 were greater (p < .05) than in W70. The individual values of the
      CSA of the left and right quadriceps femoris (QF) correlated (p < .05-.001) with
      the individual values of maximal unilateral knee extension forces in M50 (r = .87
      and r = .87), M70 (r = .61 and r = .80), W50 (r = .79 and r = .58), and W70 (r =
      .56 and r = .54). When the force values were related to the CSA of the muscle,
      W70 demonstrated a lower (p < .05) value than the other three groups. Maximal
      voluntary bilateral forces didn't differ from those of the summed unilateral
      forces, and the maximal integrated EMG values during the bilateral and unilateral
      contractions of the same leg were also the same. The results suggest that the
      decline in maximal strength with increasing age could be related to the decline
      in the CSA of the muscle, but in older people, especially women, strength
      decreases seemed to be multifactorial, including possibly a decrease in voluntary
      neural drive or changes in "qualitative" characteristics of the muscle tissue.
      Explosive strength may decrease with aging even more than maximal strength,
      suggesting that atrophying effects of aging may be greater on fast-twitch muscle
      fibers than on slow-twitch fibers and/or that the rate of neural activation of
      the muscles may also be influenced by aging. On the other hand, the central
      nervous system in a simple single joint isometric force production of the knee
      extensors seems to be capable of activation of the two bilateral QF muscle groups
      to the same degree in comparison to that of the unilateral activation only.

PMID- 8548496
TI  - Age-related dynamics of cognitive brain functions in humans: an
      electrophysiological approach.
AB  - Event-related P300 potentials closely reflect cognitive functions such as
      stimulus discrimination (N250) and processing time (P300 latencies) as well as
      attention capabilities (P300 amplitudes). To delineate the age-related dynamics
      of P300 potentials, we investigated 250 healthy subjects between 18 and 98 years
      of age in a cross-sectional study. A total of 330 visual P300 tests was performed
      in two different paradigms (PI, passive condition, n = 80; PII, active condition,
      n = 250). In both P300 paradigms, the N250 and P300 latencies were markedly
      prolonged (p < .0001) in older age, whereas the N250 and P300 latency differences
      between PII and PI did not change (p > .05). The P300 amplitudes in paradigm I
      and II revealed only a slight age-related reduction. In fact, the P300 amplitude
      ratios between PII and PI remained constant. Third-order polynomial regressions
      provided the best fit of the aging-P300 interactions in paradigms I and II for
      both males and females. Interestingly, females showed a greater and possibly
      earlier P300 latency increase during aging than males. These age-related changes
      of P300 potentials indicate a rather mild cognitive decline that does not
      accelerate before old age and may be different between both sexes.

PMID- 8548497
TI  - Hormonal responses to maximal and submaximal exercise in trained and untrained
      men of various ages.
AB  - Neuroendocrine adjustments to maximal and submaximal exercise were investigated
      in men as a function of age and training status. Twenty-four trained cyclists and
      23 sedentary men constituting a young (M = 22.9 yrs, n = 16), middle-aged (M =
      44.9 yrs, n = 16), and old (M = 65.5 yrs, n = 15) group performed both a maximal
      (GXT) and a 45-minute submaximal exercise test (cycle ergometer) at the workload
      corresponding to their lactate threshold. Plasma lactate, glucose, growth
      hormone, cortisol, norepinephrine, and epinephrine concentrations were analyzed
      both at rest and during exercise. Peak oxygen consumption (VO2 peak) was lower
      with age; however, all trained groups had higher values for VO2 peak compared to
      sedentary groups, regardless of age. Lactate threshold, when expressed in
      absolute terms, was lower with advancing age (sedentary decreases 9 and 26%:
      trained decreases 19 and 35% for middle-age and old, respectively, when compared
      to young). Pre-exercise plasma norepinephrine levels were higher with age in both
      trained and sedentary subjects. Cortisol levels were lower with age for sedentary
      subjects and were significantly elevated in trained subjects across all age
      groups. Endurance training resulted in increased hormonal responses, as measured
      by plasma concentrations, to both maximal and submaximal exercise across all age
      groups. However, regardless of training status, age-related declines were
      observed in peak responses for lactate, growth hormone, and cortisol during the
      GXT. During the 45-minute submaximal exercise test, these age-related differences
      that had been present in the GXT were abolished. This submaximal test represented
      a lower absolute work load for old compared to young as well as sedentary
      compared to trained subjects; however, individuals were working at similar
      relative exercise intensities. We conclude that older individuals are capable of
      similar hormonal responses to submaximal exercise of identical durations and
      intensities as their young and middle-aged counterparts, and that chronic
      endurance training can enhance the hormonal response to exercise in all age
      groups.

PMID- 8548498
TI  - The effect of exercise training on cold tolerance in adult and old C57BL/6J mice.
AB  - In order to ascertain the effect of aging on cross-adaptation between exercise
      training and cold tolerance, we studied cold tolerance in adult and old C57BL/6J
      male mice before and after 6 weeks of an exercise regimen of moderate intensity.
      There were two age groups of 32 mice each, including 12-month-old (adult) and 24
      month-old (aged) mice equally divided into control and exercise groups. The
      exercise consisted of daily runs on a treadmill (1 hr/day, 5 days/week) for 6
      weeks, while the control mice spent the same time on a stationary treadmill. All
      mice were subjected to a cold stress test (3-hr partial restraint at 6 degrees C)
      prior to and following the designated regimen. The results revealed a
      statistically significant interaction between age and exercise training. In adult
      mice, exercise resulted in a reduction of cold-induced heat production and
      weakening of cold tolerance, while in aged mice, the opposite effect was
      observed; i.e., an increase in cold-induced heat production accompanied by
      greater cold tolerance. However, only the attenuating effect on cold tolerance of
      adults was statistically significant. The results of our experiments do not
      support the existence of cross-adaptation between exercise training and cold
      tolerance. They indicate, however, that exercise training affects the cold
      tolerance in adult and old mice through different physiological mechanisms.

PMID- 8548499
TI  - The regeneration of noninnervated muscle grafts and marcaine-treated muscles in
      young and old rats.
AB  - Free grafts of the extensor digitorum longus (EDL) muscle in 4-month-old rats
      regenerate 2-3 times better than in 24-month-old rats. Based on these data, we
      formulated the working hypothesis that deficient reinnervation is one of the most
      important age-related environmental factors within the host that might account
      for the poor regeneration. In the present experiments, we compared the
      regeneration of EDL muscles in two groups of young and old rats: (a) 21-day
      grafts, with fibers regenerating in the absence of nerves, and (b) Marcaine
      treated muscle with fibers regenerating in the presence of uninterrupted
      innervation. The specific hypothesis was that, under each of these circumstances,
      reinnervation was not involved and age-related differences in regeneration would
      not be seen. Differences were assessed by measurements of mass and maximum
      isometric force normalized to values for age-matched control muscles. In the
      absence of nerves, the degree of regeneration in 21-day noninnervated EDL grafts
      was not significantly different between young and old rats. Similarly, when EDL
      muscles were damaged by Marcaine and regenerated in the presence of uninterrupted
      innervation, no differences were noted between young and old rats. These data
      support the working hypothesis that a deficiency in reinnervation with increasing
      age accounts, at least in part, for the poorer success of muscle regeneration in
      grafts in old compared with young rats.

PMID- 8548500
TI  - Correlates of tumor size, gender, cell type, and metastasis of resected non-small
      cell lung cancer and age.
AB  - The purpose of this retrospective study was to examine the relationship between
      tumor volume and age in resected non-small cell lung cancer (NSCLC). Differences
      exist in the behavior, growth rate, and metastatic potential of solid tumors in
      both aged humans and experimental animal models. Data from 669 cases of NSCLC
      resected between 1980 and 1992 were reviewed (445 males; 224 females; median age
      67 years, range 16-86). Measurements of the resected tumor in-situ were made in
      three dimensions, and these were multiplied to give an estimate of the tumor
      volume. Multiple regression analysis was used to examine the relationship between
      the tumor volume, age, gender, histological cell type, and TNM nodal score. No
      direct relationship existed between patient age and tumor volume or nodal score.
      However, there was a significant relationship between patient gender and tumor
      volume, i.e., smaller volume tumors in female patients (p = .02). Considering all
      variables, two relational subgroups were identified: younger male patients with
      large adenocarcinomas and older female patients with small squamous cell
      carcinomas (p = .05). We conclude that the relationship between tumor volume and
      age is complex and dependent on patient gender and tumor cell type.

PMID- 8548501
TI  - Pathologic characterization of brown Norway, brown Norway x Fischer 344, and
      Fischer 344 x brown Norway rats with relation to age.
AB  - The rat is a common laboratory animal utilized in a variety of investigations
      including experimental gerontology. Gerontologic investigations can be
      compromised when the differences observed when comparing young and old animals
      are actually differences between normal and disease states. It is of critical
      interest to know the pathology of the animals being studied and to understand the
      impact of these disease processes on the parameters being measured. The incidence
      and average age of occurrence for lesions have been characterized and are
      reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway
      x Fischer 344 and Fischer 344 x Brown Norway) of rat. Total lesion incidence
      functions as a biomaker of aging for all of the strains examined (p < or =
      .00001). These three genotypes have significantly lower incidence of several
      major pathologic processes (including glomerulonephritis, retinal atrophy, and
      leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized
      strains. Additionally, the BN and F344 x BN F1 hybrid attain 50% mortality at 130
      and 146 weeks of age, respectively, which is significantly greater than the 103
      weeks for the F344 rat. It is hoped that access to basic information on these
      three rat genotypes will increase their utilization by the community of
      gerontologic scientists.

PMID- 8548502
TI  - Increased activation of EGF-receptor tyrosine kinase by EGF and TGF-alpha in the
      colonic mucosa of aged rats.
AB  - Freshly isolated colonocytes as well as detergent-solubilized colonic mucosa and
      lectin purified receptor-enriched mucosal preparations were utilized to compare
      ligand-induced activation of EGF-receptor (EGF-R) tyrosine kinase (Tyr-k)
      activity between young (4 months) and aged (24 months) rats. In all three mucosal
      preparations, EGF and TGF-alpha produced a significantly greater stimulation in
      EGF-R Tyr-k activity in aged than in young rats, when compared with the
      corresponding basal levels. This was observed in spite of a significantly higher
      basal EGF-R Tyr-k activity in the colonic mucosa of aged rats than in young
      animals. Neither in young nor in aged rats did bombesin cause any significant
      change in EGF-R Tyr-k activity in the colonic mucosa. In aged rats, TGF-alpha
      also caused a stimulation in tyrosine phosphorylation of EGF-R and
      autophosphorylation of the 165 kDa band (a molecular mass that corresponds to EGF
      R) and several other mucosal proteins (M, 120, 110, 70, 60, 55 and 50 kDa). We
      suggest that mitogenic activation of EGF-R Tyr-k may be an important event for
      the development of hyperproliferative state in the colonic mucosa of aged rats.

PMID- 8548503
TI  - YY1 and Sp1 transcription factors bind the human transferrin gene in an age
      related manner.
AB  - The iron-binding protein transferrin has major roles in transporting, delivering,
      and sequestering ferric ions acquired by body tissues. Yet, during aging, serum
      transferrin levels decrease in humans. Likewise, in transgenic mice carrying
      chimeric human transferrin transgenes, liver expression of transferrin transgenes
      decreases with age. The aging regulation is due to decreased gene transcription.
      Electrophoretic mobility shift assays and antibody-recognition have revealed the
      binding of 5' regulatory elements of the human transferrin gene by three YY1
      proteins, called YY1, YY1-a, and YY1-b, and an Sp1-a transcription factor. An age
      related increase in YY1-a and YY1-b binding activities and a decrease in Sp1-like
      binding activity were shown. Since Sp1 is a positive transcription factor and YY1
      can be a negative transcription factor, the alterations in their binding with age
      could cause the decreased transcription of the human transferrin transgene, and
      also the age-related decreased serum transferrin levels in humans.

PMID- 8548504
TI  - Reciprocal expression of P-glycoprotein and TAP1 accompanied by higher expression
      of MHC class I antigens in T cells of old mice.
AB  - We have shown previously that (a) aging leads to an increase in the proportion of
      murine splenic T cells that express high activity of P-glycoprotein (PGP), the
      ATP-dependent plasma membrane pump that mediates multiple drug resistance, and
      (b) PGPhi CD4 memory cells from mice of any age do not proliferate or secrete IL
      4 after activation with anti-CD3 and IL2. We now report that the age-associated
      increase in expression of MHC Class I molecules is limited to the subset of T
      cells that overexpress PGP and thus extrude the fluorochrome R123 (the "R123lo"
      subset). Although H-2 levels increase on T cells of old mice, the levels of TAP1,
      a component of the polypeptide pump responsible for assembly and internal
      transport of Class I MHC molecules, decline, unexpectedly, by about fourfold in T
      cells from old donors. Thus, aging leads to reciprocal changes in the level of T
      cell expression of PGP and TAP1, two closely related members of the ABC
      superfamily of peptide transport proteins.

PMID- 8548505
TI  - Growth hormone-releasing hormone depletion in the female rat: similarities to
      aging.
AB  - The age-related decline in growth hormone (GH) secretion has been largely
      attributed to age-related degeneration of hypothalamic growth hormone-releasing
      hormone (GHRH)-producing neurons. GH decline has recently been linked to age
      related bone changes in humans. Bone loss and decreased bone strength are common
      in aging rats and humans, but density of remaining mineral tissue is known to be
      increased. The effect of induced hypothalamic GHRH deficiency on bone was
      assessed, and similarities between bone changes encountered and those taking
      place in aging were identified. Female rats received monosodium glutamate (MSG)
      following birth, and they were euthanized at 19 weeks of age. Femurs from MSG
      treated rats had greater mineral density (p < .05), greater mineral/matrix ratio
      (p < .01), lower mineral apposition rate (p < .005), and lower bone formation
      rate (p < .05). These results suggest that hypothalamic GHRH decline plays a
      substantial role in the development of bone pathology similar to that observed in
      aging individuals.

PMID- 8548506
TI  - Age and systemic acid-base equilibrium: analysis of published data.
AB  - To investigate whether systemic acid-base equilibrium changes with aging in
      normal adult humans, we reviewed published articles reporting the acid-base
      composition of arterial, arterialized venous, or capillary blood in age
      identified healthy subjects. We extracted or calculated blood hydrogen ion
      concentration ([H+]), plasma bicarbonate concentration ([HCO3(-)]), blood PCO2,
      and age, and computed a total of 61 age-group means, distributed among eight 10
      year intervals from age 20 to 100 years. Using linear regression analysis, we
      found that with increasing age, there is a significant increase in the steady
      state blood [H+] (p < .001), and reduction in steady-state plasma [HCO3(-)] (p <
      .001), indicative of a progressively worsening low-level metabolic acidosis.
      Blood PCO2 decreased with age (p < .05), in keeping with the expected respiratory
      adaptation to metabolic acidosis. Such age-related increasing metabolic acidosis
      may reflect in part the normal decline of renal function with increasing age. The
      role of age-related metabolic acidosis in the pathogenesis of the degenerative
      diseases of aging warrants consideration.

PMID- 8548507
TI  - Antioxidants and reduced functional capacity in the elderly: findings from the
      Nun Study.
AB  - BACKGROUND: This study investigated the relationship of plasma antioxidants to
      reduced functional capacity in the elderly. A hallmark of reduced functional
      capacity in the elderly is dependence in self-care (i.e., requiring assistance
      with bathing, walking, dressing, standing, toileting, and feeding). METHODS: This
      relationship was assessed in a cross-sectional study of 88 Catholic sisters
      (nuns). These 77- to 98-year-old women lived in the same building, ate food
      prepared in the same kitchen, and had all nursing services provided by the same
      staff. In 1993, ability to perform self-care was assessed, and blood was drawn to
      determine plasma carotenoids (lycopene, beta carotene, alpha carotene, zeaxanthin
      and lutein combined, and beta cryptoxanthin) and alpha tocopherol. RESULTS:
      Dependence in self-care had a strong negative association with lycopene, but was
      not clearly related to other carotenoids or alpha tocopherol. Results from age
      adjusted least squares regression indicated that a 30 micrograms/dl decrease in
      lycopene was associated with 2.4 additional dependencies in self-care (95%
      confidence interval = 1.5, 3.3; p < .001). Lycopene's relationship to dependence
      was modified by plasma LDL-cholesterol, the predominant carrier of lycopene in
      the blood. Women with low lycopene and low LDL-cholesterol had 3.6 dependencies
      (95% confidence interval = 3.1, 4.2; p < .001), compared to 1.0 dependency (95%
      confidence interval = 0.3, 1.8) in those with high lycopene and low LDL
      cholesterol. CONCLUSIONS: This is the first study to report an association
      between lycopene and functional status. This finding needs to be replicated in
      other human and animal studies before the association is accepted as real.

PMID- 8548508
TI  - Changes in spinal reflexes preceding a voluntary movement in young and old
      adults.
AB  - BACKGROUND: Age-related differences in spinal excitability during response
      preparation were assessed by eliciting either a 50% H-reflex or an Achilles
      tendon reflex preceding the onset of a right plantar flexion contraction in 20
      young adults (23.1 +/- 1.64 yrs) and 20 old adults (68.5 +/- 5.53 yrs). METHODS:
      On each simple reaction time trial, the test reflex was elicited at a specific
      test interval during either the foreperiod or the response period. The foreperiod
      test intervals were 500, 600, 700, 800, 900, and 1000 msec after the presentation
      of the warning stimulus. The response period test intervals were 50, 100, 150,
      200, 250, and 300 msec after the presentation of the response stimulus. Control
      reflexes were randomly elicited between the simple reaction time trials. RESULTS:
      Changes in reflex excitability were not observed during the foreperiod in either
      age group. During the response period, the percentage of H-reflex facilitation as
      compared to control H-reflexes was similar for the young (68%) and the old (61%)
      adults, but the magnitude of Achilles tendon reflex facilitation with respect to
      control reflex responses was greater in the young adults (74%) than in the old
      adults (38%). The time course of H- and tendon reflex facilitation was delayed in
      the old group during the response period. CONCLUSIONS: The results indicate that
      processes underlying the preparation and generation of a motor response are
      similar in young and old adults. However, these processes occur at a slower rate
      in old adults.

PMID- 8548509
TI  - Why do exercise-induced ventricular arrhythmias increase with age? Role of M-mode
      echocardiographic aging changes.
AB  - BACKGROUND: Although advancing age is associated with a higher prevalence and
      complexity of exercise-induced ventricular arrhythmias (EIVA), the role of age
      associated cardiac anatomic and functional characteristics in this relationship
      has not been explored. METHODS: We performed both M-mode echocardiography and
      maximal treadmill exercise testing within two consecutive visits in 366 healthy
      volunteers ages 20 to 90 years from the Baltimore Longitudinal Study of Aging.
      RESULTS: Simple (i.e., isolated) EIVA were detected in 79 subjects (21%) and
      complex EIVA (i.e., EIVA comprising > or = 10% of beats in any minute or
      occurring in runs) in another 17 (5%). Univariate predictors of any EIVA, whether
      simple or complex, were older age (p < .0001), greater LV mass index (p < .0001),
      male gender (p < .001), higher peak exercise systolic blood pressure (p = .003),
      and larger body surface area (p = .005). By multiple logistic regression
      analysis, only age (p = .0001) independently predicted the occurrence of EIVA.
      For complex EIVA alone, the strongest univariate predictors were age (p = .004),
      male gender (p = .008), lower maximal heart rate (p = .01), greater left atrial
      size (p = .03), and larger LV posterior wall thickness (p = .04); on multiple
      logistic regression, only older age (p = .03) and larger left atrial size (p =
      .04) independently predicted the presence of complex EIVA. CONCLUSION: In healthy
      volunteers undergoing maximal treadmill exercise, greater LV wall thickness and
      mass are associated with the development of EIVA but they do not independently
      predict EIVA once the powerful effect of age is considered. The association
      between complex EIVA and left atrial dilatation may be mediated by higher LV end
      diastolic pressure and volume during exercise in subjects with larger left atria.

PMID- 8548510
TI  - Functional and residential status transitions among nursing home residents.
AB  - BACKGROUND: The present study examines transitions in the functional status and
      discharge destination of new nursing home admissions who remain at least 100
      days, and ascertains baseline covariates associated with transition patterns.
      METHODS: Using a fully observed, continuous-time Markov chain model for maximum
      likelihood estimation of probability intensities, transition processes are
      characterized. The long-stay cohort (n = 9,541) was derived from a sample of
      elders newly admitted to 48 National Health Corporation (NHC) nursing homes
      between 1983 and 1987. Assessment of functional status, using a modified Katz ADL
      scale, occurred during the first, second, and third months, and the second,
      third, and fourth quarters after admission. Four types of residential changes
      (e.g., mortality) were examined for the latter three quarters. RESULTS: While
      stability was the predominant pattern during the first 90 days in the nursing
      home, 51.5% of residents experienced a change in function. The probability of
      change was higher for modest (one level) rather than substantial change, and for
      such change to represent improvement rather than decline. Over 25% of this long
      stay sample exited in the second quarter, 37% of them returning home. The rates
      for returns to home and for mortality were strongly related to functional level.
      Several sociodemography variables (e.g., age, source of payment), diagnostic
      indicators (e.g., cancer), and orientation status were consistently associated
      with transition rates within functionally homogeneous groups. CONCLUSIONS:
      Overall, findings underscore the heterogeneity and complexity of transition
      patterns for a subgroup historically treated as likely to decline or remain
      stable, and viewed as "permanent" residents. The model was useful in describing
      the volatile transition process among older long-stayers.

PMID- 8548511
TI  - Changes in cortisol and growth hormone secretion during nocturnal sleep in the
      course of aging.
AB  - BACKGROUND: One current hypothesis of biological aging proposes that aging
      results from the deterioration of neuroendocrine functions. Sleep dependent
      growth hormone (GH) secretion is diminished in elderly people. However, the time
      course of this decrease from puberty to senescence is still unknown. Cortisol
      secretion is also related to sleep processes with the 24 hr nadir occurring, like
      the sleep dependent GH secretory surge, during the first half of nocturnal sleep.
      Whether age also affects the sleep-associated nadir of cortisol secretion has yet
      to be clarified. This study investigated changes in GH and cortisol secretion
      during sleep in 30 male volunteers age 20 to 92 yr. METHODS: After an adaptation
      night, each subject spent another night in the sleep laboratory for polygraphic
      sleep recording and determination of GH and cortisol levels every 15 min.
      RESULTS: GH peak values exponentially decreased with age (r = -.80, p < .001),
      while the cortisol nadir increased linearly as a function of age (r = .79, p <
      .001). Age-related changes in sleep-dependent secretion of GH and cortisol
      correlated significantly (r = .47, r = -.55, respectively; p < .05) with an age
      dependent decrease in slow wave sleep. CONCLUSION: Alterations of GH peak
      amplitude and basal cortisol secretion are not restricted to senescence. These
      changes develop gradually during adult life with different time courses. Both
      changes in GH and cortisol secretion may act together to reduce anabolic
      functions of sleep in the aged.

PMID- 8548512
TI  - Psychological indicators of balance confidence: relationship to actual and
      perceived abilities.
AB  - BACKGROUND: This study compares several psychological indicators of balance
      confidence in relation to physical performance, past and current experience,
      gender bias, and other perceptions of daily functioning. METHODS: Sixty community
      dwelling ambulatory elders (aged 65-95) were administered the Falls Efficacy
      Scale (FES), the Activities-Specific Balance Confidence Scale (ABC), and three
      dichotomous questions on fear of falling, activity avoidance, and perceived need
      for personal assistance to ambulate outdoors. Performance measures on walking
      (average speed) and balance (static posturography) were obtained on a subsample
      of 21 subjects. RESULTS: Balance confidence assessed by the ABC and self
      perceived need for personal assistance with outdoor ambulation were the only
      indicators significantly associated with the performance measures. As expected,
      perceived balance capabilities were more strongly related to current behavior
      (frequency of doing specific activities) than to past experience (fall history).
      Gender differences in self-report emerged for the global fear-of-falling
      indicator but not for the two efficacy ratings. CONCLUSIONS: Psychological
      indicators of balance confidence are important to measure both in conjunction
      with balance test performance and as a legitimate focus of rehabilitation. Of the
      various indicators assessed here, the dichotomous fear-of-falling question
      appears to have the least utility. Perceived need for personal assistance to
      ambulate outdoors has merit as an initial clinical screening question for
      discriminating persons on the basis of both physical ability and confidence. The
      ABC scale appears to have the greatest utility as an evaluative index for older
      persons at a moderate to high level of functioning.

PMID- 8548513
TI  - Stress, gender, cognitive impairment, and outpatient physician use in later life.
AB  - The purpose of this study was to look at the interface between stressful life
      events, gender, cognitive impairment, and the use of outpatient physician
      services among older adults. A theoretical rationale is presented, suggesting
      that older men who are suffering from either mild or moderate levels of cognitive
      impairment are especially likely to use outpatient physician services when they
      are confronted by undesirable stressful events. Analyses with data provided by a
      nationwide sample of elderly people provide support for this complex three-way
      interaction.

PMID- 8548514
TI  - Self-efficacy and pain in disability with osteoarthritis of the knee.
AB  - This study examined the relationship between self-efficacy beliefs and pain
      during the performance of stair climbing and lifting/carrying tasks on speed of
      movement, ratings of task difficulty, and perceived task ability in a group of
      patients with osteoarthritis (OA) of the knee. Seventy-nine patients with knee OA
      completed the tasks in a controlled laboratory setting. Before completing each
      task, patients' self-efficacy was assessed; following task performance they rated
      (a) the most intense knee pain experienced, (b) the difficulty of the task, and
      (c) their perceived ability as they performed each task. Results demonstrated
      that, even after controlling for physical function, self-efficacy, and knee pain
      during performance, each contributed significantly to understanding either speed
      of movement or self-reported ratings of task difficulty and perceived ability.

PMID- 8548515
TI  - Observed affect in nursing home residents with Alzheimer's disease.
AB  - A method for assessing affect states among older people with Alzheimer's disease
      was developed for use in a study designed to evaluate a special care unit for
      such residents of a nursing home. The 6-item Philadelphia Geriatric Center Affect
      Rating Scale was designed for the use of research and other staff in assessing
      positive affect (pleasure, interest, contentment) and negative affect (sadness,
      worry/anxiety, and anger) by direct observation of facial expression, body
      movement, and other cues that do not depend on self-report, among 253 demented
      and 43 nondemented residents. Each affect scale was highly reliable, expressed in
      estimated portions of a 10-minute observation period when the affect expression
      occurred. Validity estimates were affirmative in showing discriminant
      correlations between the positive states and various independent measures of
      social and other outwardly engaged behavior and between negative states and other
      measures of depression, anger, anxiety, and withdrawal. Limited support for the
      two-factor dimensionality of the affect ratings was obtained, although positive
      and negative affect were correlated, rather than independent. Some hope is
      offered that the preference and aversions of Alzheimer patients may be better
      understood by observations of their emotional behaviors and that such methods may
      lead to a better ability to judge institutional quality.

PMID- 8548516
TI  - General and specific speed mediation of adult age differences in memory.
AB  - The proposal that age-related differences in some measures of speed of
      performance may not be independent of the age-related differences in other
      measures of speed of performance has been associated with considerable
      controversy. Because converging evidence can often resolve this type of
      controversy, correlation-based procedures are proposed to distinguish general (or
      common) and specific (or unique) age-related influences on measures of speeded
      performance. Results from three earlier studies and from a new study suggest that
      a large proportion of the age-related variance in a wide range of speed measures
      is shared and is not distinct. Furthermore, the common or general speed factor
      appears to play an important role in the mediation of age-related differences in
      memory.

PMID- 8548517
TI  - Social support in the context of caregiving: husbands' provision of support to
      wives involved in parent care.
AB  - The purpose of this study was to identify ways in which social support is related
      to the caregiving stress and well-being experienced by adult daughter caregivers.
      The study focused on a specific source of support, caregivers' husbands, and
      included reports from 126 caregivers and their husbands. Main and buffering
      effects of four types of support (emotional and instrumental support provided to
      the caregiver and to her parent) were tested, and caregiver's level of optimism
      was controlled. Results were similar for caregivers' and husbands' accounts of
      support. Buffering effects were found only for physical health, whereas effects
      opposite those predicted by the buffering hypothesis were detected for positive
      affect. A main effect was found in nearly all analyses of marital satisfaction.
      No main or buffering effects of support were detected for depression. Findings
      highlight the complexity of supportive exchanges by illustrating the simultaneous
      operation of different types of support and their distinctive impact on the
      caregiving stress and well-being relationship.

PMID- 8548518
TI  - Race inequities in men's retirement.
AB  - A multistate life table model is used to identify how labor force experiences and
      mortality determine the labor force participation rates (LFPRs) and the qualities
      of the retirement life cycle of Black and White older men. LFPRs and the life
      cycle measures are compared to assess inequities of retirement access for the
      racial groups. The results show that Blacks' lower LFPRs are a function of
      disability. Despite lower LFPRs than Whites, however, Blacks spend a greater
      portion of their lives both working and disabled, reducing the retirement period.
      Race differences in the retirement life cycle also are highly sensitive to
      mortality. Reducing Black mortality to that of Whites would substantially narrow
      the life cycle differences. The combination of higher disability and mortality
      rates among Blacks suggests that health is a key determinant of retirement
      inequity.

PMID- 8548519
TI  - Gender differences in employment behavior during late middle age.
AB  - Gender differences in the employment rates of 55- to 59-year-olds are
      concentrated among married persons. Wives are much less likely than their
      husbands to hold jobs and, more often, to cite family motivations as their most
      important reason for not working. The employment disparity is partially the
      result of the coordinated retirement decisions (combined with men typically
      marrying younger women), and is probably reinforced by the heavier caregiving
      commitments of females. Several findings are consistent with traditional role
      relationships, which emphasize specialization in market employment by males and
      home activities among females; however, the data are less compatible with a
      simple pattern where husbands "lead" and wives "follow".

PMID- 8548520
TI  - Gender and life satisfaction in retirement: an assessment of the male model.
AB  - This study seek to extend the research on retirement in two ways. First, using a
      nationally representative sample, I attempt to clarify the relationship between
      gender and life satisfaction in retirement by explicitly considering how gender
      structures preretirement employment experiences. Second, I ask whether the "male
      model" of life satisfaction in retirement can be used to assess women's life
      satisfaction in retirement. It is hypothesized that employment structures,
      through their influence on sources of work satisfaction and world view, influence
      the sources of life satisfaction in retirement. While this hypothesis is
      generally supported, gender still appears to define a context for the variables
      of the male model beyond that encompassed by employment structures. The sources
      and implications of this gender influence for future social gerontological
      research, particularly in the area of retirement, are discussed.

PMID- 8548521
TI  - Age differences and age changes in activities: Baltimore Longitudinal Study of
      Aging.
AB  - This study examines cross-sectional age differences, longitudinal age changes,
      and secular changes in obligatory, committed, and discretionary activities, using
      activity questionnaire completed by men and women participants in the Baltimore
      Longitudinal Study of Aging between 1958 and 1992. (1) Time spent, on obligatory
      activities and passive leisure is greatest, and on committed activities and
      active leisure least, for older adults. (2) Longitudinal patterns usually mirror
      cross-sectional ones. There are pronounced exceptions for women whose paid work
      time has been increasing and housework decreasing, while cross-sectional patterns
      show the reverse. (3) Over recent decades, time in committed activities shifted
      in opposite ways for men and women. Men decreased paid work and increased
      housework, repairs and yardwork, shopping, and child-care, while women increased
      paid work and decreased housework. In sum, the age structure of activities has
      persisted in the midst of new social opportunities; gender roles have proven more
      malleable than age roles.

PMID- 8548522
TI  - Living arrangements of minority elders.
AB  - We used 1990 census data to examine differences in the current living
      arrangements of minority elderly. We found that differences among the minority
      populations in age, sex, and marital status account for only a small part of the
      observed differences in living arrangements. However, while minority groups as a
      whole differ substantially from the White population, national ethnic patterns
      within groups appear to be relatively small. Hispanic ethnic groups vary little
      once differences in marriage patterns are taken into account, although
      differences are greater within the Asian population.

PMID- 8548523
TI  - Electromagnetic field exposure and cancer: a review of epidemiologic evidence.
AB  - The idea that exposure to power-frequency electric and magnetic fields might
      contribute to cancer causation has been under investigation for nearly two
      decades. A number of epidemiologic studies have been undertaken, but findings
      have been weak, inconsistent, and inconclusive. This article provides an updated
      survey of epidemiologic information and considers those data in relation to the
      many scientific uncertainties that still persist.

PMID- 8548524
TI  - Cancer statistics: a measure of progress.

PMID- 8548525
TI  - Wilms tumor.
AB  - Wilms tumor is the most common primary malignant renal tumor of childhood,
      representing about six percent of all childhood cancers in the United States.
      Developments in surgery, radiation therapy, and chemotherapy have led to a
      dramatic change in the prognosis for most patients, and Wilms tumor has become a
      paradigm for multimodal treatment of a pediatric malignant solid tumor. The
      authors review the progress made in the diagnosis and management of children with
      Wilms tumor.

PMID- 8548526
TI  - Cancer statistics, 1996.
AB  - The American Cancer Society's Department of Epidemiology and Statistics reports
      its 30th annual compilation of cancer incidence, survival, and mortality data for
      the United States and around the world.

PMID- 8548527
TI  - Clinical utility of complement assessment.

PMID- 8548528
TI  - X-linked severe combined immunodeficiency disease and the gamma c receptor
      component: prospects for molecular diagnosis.

PMID- 8548529
TI  - Nitrocellulose immunoblotting for identification and molecular gene cloning of
      Eimeria maxima antigens that stimulate lymphocyte proliferation.
AB  - An immunoblotting technique was used to identify lymphostimulatory antigens
      within sized polypeptide fractions of Eimeria maxima sporozoites. Six fractions
      contained polypeptides that specifically stimulated the proliferation of immune
      lymphocytes in an in vitro assay, and polyclonal antisera were made in rabbits
      against these fractions. cDNA clones, isolated with antisera against a
      lymphostimulatory fraction of around 70 kDa, were found to encode four different
      antigens including a classical hsp70, a molecule homologous to an endoplasmic
      reticulum chaperonin (BiP/GRP), and a calcium-dependent serine/threonine protein
      kinase that appears homologous to a recently described molecule from Plasmodium
      falciparum. The protein kinase cDNA clone was overexpressed in Escherichia coli,
      and the recombinant antigen was found to induce both antibody and
      lymphoproliferative responses in chickens when administered subcutaneously. Thus,
      immunoblotting, in combination with in vitro lymphoproliferation assays, can be
      used as an initial screen for the identification of lymphostimulatory antigens
      from a complex pool of polypeptides, and a combination of cDNA cloning,
      expression, and immunization allows assessment of the lymphostimulatory activity
      of individual polypeptides. These studies should facilitate further evaluation of
      antigens that are potential candidates for inclusion in a recombinant vaccine
      against poultry coccidiosis.

PMID- 8548530
TI  - Monoclonal antibodies to Coxiella burnetii that cross-react with strain Nine
      Mile.
AB  - Results are presented to show the binding properties of five monoclonal
      antibodies directed to Coxiella burnetii Priscilla with cross-reactions to the
      Nine Mile strain. The monoclonal antibodies preferentially recognize phase I
      epitopes by ELISA and recognize phase II epitopes by immunoblotting but do not
      allow differentiation between so-called chronic and acute strains of C. burnetii.
      The only difference in reactivity was in the staining pattern revealed after
      reactions with lipopolysaccharide I antigens.

PMID- 8548531
TI  - Immune complex transfer enzyme immunoassay that is more sensitive and specific
      than western blotting for detection of antibody immunoglobulin G to human
      immunodeficiency virus type 1 in serum with recombinant pol and gag proteins as
      antigens.
AB  - Antibody immunoglobulin G (IgG) to human immunodeficiency virus type 1 (HIV-1) in
      serum was detected by ultrasensitive enzyme immunoassays (immune complex transfer
      enzyme immunoassays) with recombinant reverse transcriptase (rRT), p17 (rp17) and
      p24 (rp24) of HIV-1 as antigens and beta-D-galactosidase from Escherichia coli as
      the label. The immune complex, comprising 2,4-dinitrophenyl-bovine serum albumin
      recombinant protein conjugate, antibody IgG to HIV-1, and recombinant protein
      beta-D-galactosidase conjugate, was trapped on polystyrene beads coated with
      affinity-purified (anti-2,4-dinitrophenyl group) IgG, eluted with epsilon N-2,4
      dinitrophenyl-L-lysine, and transferred to polystyrene beads coated with affinity
      purified (anti-human IgG gamma-chain) IgG. Bound beta-D-galactosidase activity
      was assayed by fluorometry. The assays were highly reproducible with no serious
      serum interference, and they were much more sensitive than Western immunoblotting
      for the corresponding antigens. Signals with rRT, rp17, and rp24 for asymptomatic
      carriers were at least 56,000-, 680-, and 22-fold higher, respectively, than
      those for seronegative individuals, and neither indeterminate nor false-positive
      results were observed, whereas some serum samples were false negative or false
      positive by Western blotting for p17 and/or p24 antigen. In some cases,
      seroconversion was detected earlier than by conventional methods. Therefore,
      these assays are suggested to be more useful than conventional methods not only
      for the confirmation of antibody IgGs to RT, p17, and p24 of HIV-1 in serum but
      also for the detection of seroconversion.

PMID- 8548532
TI  - Monoclonal rat antibodies directed against Toxoplasma gondii suitable for
      studying tachyzoite-bradyzoite interconversion in vivo.
AB  - We previously reported the in vitro analysis of stage differentiation of
      Toxoplasma gondii in murine bone marrow-derived macrophages. The purpose of this
      study was to generate monoclonal rat antibodies that might be suitable for
      investigating tachyzoite-bradyzoite interconversion in vivo with the murine
      model. Immunization of Fischer rats with cysts of T. gondii NTE resulted in the
      generation of seven monoclonal antibodies of the immunoglobulin G2a, G2b, or M
      isotype, which were further characterized by the immunoblot technique,
      immunofluorescence assay, immunohistology, and immunoelectron microscopy.
      Immunoblots demonstrated specific reactivity of five monoclonal antibodies with
      proteins with molecular masses of 40, 52, 55, 60, 64, 65, and 115 kDa. One
      antibody (CC2) appeared to recognize a differently expressed antigen depending on
      the parasite stage, reacting with a 40-kDa molecule in tachyzoites and a 115-kDa
      antigen in bradyzoites and oocysts. Several other monoclonal antibodies were
      shown to be stage specific and to react in immunofluorescence assays or in
      immunoblots with either tachyzoites or bradyzoites. Kinetics of stage conversion
      in vitro could be monitored by immunofluorescence with two of these monoclonal
      antibodies. Preliminary immunohistological investigations of tissue sections from
      infected mice demonstrated the possible usefulness of these monoclonal antibodies
      for future in vivo studies on stage differentiation of T. gondii in the murine
      system.

PMID- 8548533
TI  - Pattern of cytokines and pharmacomodulation in sepsis induced by cecal ligation
      and puncture compared with that induced by endotoxin.
AB  - The production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL
      1 beta), and IL-6 and their pharmacomodulation were evaluated in a model of
      polymicrobial sepsis induced in mice by cecal ligation and puncture (CLP) and
      were compared with the effects of endotoxin (lipopolysaccharide [LPS]) treatment.
      LPS levels rose as early as 1 h after CLP and increased further after 2 and 21 h.
      TNF-alpha was detectable in serum, spleen, liver, and lungs during the first 4 h,
      with a peak 2 h after CLP. IL-1 beta was measurable in serum after 24 h, and
      levels increased significantly in spleen and liver 4 and 8 h after CLP. IL-6
      levels increased significantly in serum throughout the first 16 h after CLP.
      These cytokines were detectable after LPS injection, with kinetics similar to
      those after CLP but at a significantly higher level. To cast more light on the
      differences between these two animal models of septic shock, we studied the
      effects of different reference drugs. Pretreatment with dexamethasone (DEX);
      ibuprofen (IBU), an inhibitor of cyclooxygenase; and NG-nitro-L-arginine, an
      inhibitor of nitric oxide synthase, significantly reduced survival, while
      chlorpromazine (CPZ) and TNF did not affect it. Only the antibiotics and
      pentoxifylline significantly increased survival in mice with CLP. However, CPZ
      and DEX protected the mice from LPS mortality. On inhibiting TNF-alpha with DEX,
      CPZ, or pentoxifylline, survival was reduced, unchanged, and increased,
      respectively, and on increasing TNF-alpha with IBU and TNF, survival was
      decreased or unchanged, respectively, suggesting that the modulation of this
      cytokine does not play a significant role in sepsis induced by CLP, unlike
      treatment with LPS. The negative effects of IBU and N(G)-nitro-L-arginine suggest
      a protective role by prostaglandins and nitric oxide in sepsis induced by CLP.

PMID- 8548534
TI  - Prevalence of gca, a gene involved in synthesis of A-band common antigen
      polysaccharide in Pseudomonas aeruginosa.
AB  - Two distinct forms of lipopolysaccharide are expressed by Pseudomonas aeruginosa.
      These forms are known as the A band and the B band. In an attempt to obtain a
      better understanding of A-band lipopolysaccharide synthesis, a previously
      isolated A-band gene known as the gca gene (GDP-D-mannose conversion protein for
      A-band common antigen polysaccharide) was sequenced and analyzed. Previous
      protein expression data from our laboratory, along with nucleotide sequence
      analysis from the present study, suggest that the Gca protein is encoded by the
      open reading frame ORF36.5. Amino acid homology reveals that this protein may be
      functioning as a dehydratase or as a bifunctional enzyme, facilitating the
      conversion of GDP-D-mannose to GDP-D-rhamnose. The distribution of this gca gene
      among the 20 P. aeruginosa O serotypes, clinical isolates, and other Pseudomonas
      species was also examined. Southern hybridization results revealed that the gca
      gene is present and conserved on a 1.6-kb KpnI fragment among all 20 O serotypes
      with the exception of serotype O12. In addition, the gca gene is not universally
      found among all pseudomonads; however, probe-reactive profiles are similar to
      that of P. aeruginosa when the gca gene is present. Primers were designed from
      the gca nucleotide sequence, and PCR amplification of a 700-bp product was found
      with each of the 20 O serotypes. Because of the conservation of this gene, gca
      may be useful as a diagnostic tool for detecting the presence of P. aeruginosa as
      well as other Pseudomonas species.

PMID- 8548535
TI  - Evidence obtained with monoclonal antibodies that O antigen is the major antigen
      responsible for the cross-reactivities between serotypes 4 and 7 of
      Actinobacillus (Haemophilus) pleuropneumoniae.
AB  - Monoclonal antibodies (MAbs) against Actinobacillus (Haemophilus)
      pleuropneumoniae serotype 4 (reference strain M62 and field isolate F6) were
      produced and characterized. Three hybridoma clones were raised against strain
      M62, and 13 were raised against strain F6. The predominant antibody class was
      immunoglobulin M (IgM), although IgG2a and IgG2b were also obtained. Three of the
      MAbs produced to field isolate F6 (5C5, 1E10, and 5H7) did not recognize the
      reference strain of serotype 4, another (6F7) was reactive with both reference
      strains of serotypes 4 and 7, and the remaining 12 MAbs reacted only with the
      reference strain of the homologous serotype. All epitopes recognized by MAbs,
      except for one (6F7), were sensitive to periodic acid oxidation, and all of them
      were resistant to boiling in the presence of sodium dodecyl sulfate and reducing
      conditions, as evidenced by immunodot. Enhanced chemioluminiscence-immunoblot
      assays revealed that 10 MAbs (3E12, 5B8, 7C3, 6F7, 7F5, 7E6, 5G4, 4F1, 7E10, and
      4B8) recognized a ladder-like banding pattern, which is in accordance with the O
      side chain antigen of lipopolysaccharide (LPS), while the remaining 6 MAbs (5C5,
      5H7, 1E10, 6D11, 6B4, and 5E4) blotted with high-molecular-weight regions
      composed of a single banding pattern. The suitability of MAbs for serotyping of
      78 field isolates was also examined. A high correlation was found between the
      results previously established by indirect hemagglutination with polyclonal sera
      and those obtained by enzyme-linked immunosorbent assay with MAbs. According to
      the different immunoreactivity of MAbs, three groups were established: group I
      (MAbs 3E12, 5B8, 7C3, 6F7, and 7F5), group II (MAbs 7E6, 5G4, 4F1, 7E10, and
      4B8), and group III (MAbs 5C5, 5H7, and 1E10). MAbs 6D11, 6B4, and 5E4 could not
      be included in any of the described above. At least six different immunodominant
      epitopes on the O antigen of the A. pleuropneumoniae serotype 4 LPS were
      identified. Finally, the implications of the effect of the O antigen of LPS in
      cross-reactions between serotypes 4 and 7 are clearly evidenced.

PMID- 8548536
TI  - Flow cytometry, a new approach to detect anti-live trypomastigote antibodies and
      monitor the efficacy of specific treatment in human Chagas' disease.
AB  - Sera from patients chronically infected with Trypanosoma cruzi display antibodies
      that bind to epitopes of living trypomastigotes, known as lytic antibodies (LA),
      and are detected by a complement-mediated lysis test. Conventional serology
      antibodies (CSA) are also present in sera from patients with chronic infections
      but, in contrast to LA, are unable to recognize viable trypomastigotes. The
      presence of LA has been used as an important element in the criterion of cure in
      human Chagas' disease. Using flow cytometry technology, we introduced a new and
      sensitive immunomethod for the detection of anti-live trypomastigote membrane
      bound antibodies. On the basis of serological tests (LA and CSA detection) and
      parasitological assays such as hemoculture (HE), patients were classified into
      the following groups: chronically infected untreated patients (NT) and treated
      not-cured patients (TNC), with positive HE and both LA and CSA in their sera;
      "dissociated" HE-negative patients (DIS), in whom LA was not detected whereas CSA
      were present; a group of cured HE-negative patients (CUR), who were both LA and
      CSA negative; and, as control, a group of non-chagasic individuals (NC). Sera
      from these patients were assayed by incubation with live bloodstream
      trypomastigotes, which were subsequently exposed to fluorescein isothiocyanate
      conjugated anti-human immunoglobulin G. The parasites were then fixed, run in the
      cytometer, and identified on basis of their size and granularity gain
      adjustments. On the basis of experience with the complement-mediated lysis test,
      a level of 20% of parasites being fluorescein isothiocyanate fluorescence
      positive was used as a cutoff between effective and ineffective treatments. With
      this criterion, our results indicated that sera from NT and TNC patients were
      antibody positive whereas all sera from DIS, CUR, and NC patients did not contain
      membrane-bound antibodies. This new approach is a tool to easily identify anti
      live T. cruzi membrane-bound antibodies that can be used to monitor the efficacy
      of Chagas' disease treatment.

PMID- 8548537
TI  - Antibody responses to the capsular polysaccharide of Neisseria meningitidis
      serogroup B in patients with meningococcal disease.
AB  - We measured antibody responses to meningococcal serogroup B (MenB) polysaccharide
      (PS) by enzyme-linked immunosorbent assay (ELISA) in sera from 94 patients from
      The Netherlands with disease caused by Neisseria meningitidis group B. The
      patients ranged in age from 3 to 73 years (mean age, 18.8 years). In initial
      studies we showed that the binding of a panel of MenB PS-reactive human
      immunoglobulin M (IgM) paraproteins to biotinylated MenB PS bound to avidin
      coated microtiter wells was inhibited > 90% by the addition of soluble MenB PS or
      encapsulated group B meningococci. In contrast, inhibition of IgM anti-MenB PS
      antibody-binding activity in many of the patient sera was less than 50% (range,
      20 to 94%). These data suggested a high frequency of nonspecific binding in the
      patient sera. Therefore, all serum samples were assayed in replicate in the
      presence or absence of soluble MenB PS, and only the inhibitable fraction of the
      binding signal was used to calculate the anti-MenB PS antibody concentrations. In
      17 control patients with meningococcal disease caused by serogroup A or C
      strains, there was no significant difference in the respective IgM or IgG anti
      MenB PS antibody concentrations in paired acute- and convalescent-phase sera. In
      contrast, in patients with MenB disease, the geometric mean IgM anti-MenB PS
      antibody concentration increased from 3.9 units/ml in acute-phase serum to 10.5
      units/ml in convalescent-phase serum (P < 0.001). The corresponding geometric
      mean IgG anti-MenB PS antibody titers were 1:27 and 1:36 (P < 0.05). There was
      only a weak relationship between age and the magnitude of the logarithm of the
      antibody concentrations in convalescent-phase sera (for IgM, r2 = 0.06 and P <
      0.05; for IgG, r2 = 0.08 and P < 0.01). Our data indicate that precautions are
      needed to avoid nonspecificity in measuring serum antibody responses to MenB PS
      by ELISA. Furthermore, although this PS is thought to be a poor immunogen,
      patients as young as 3 years of age recovering from MenB disease demonstrate both
      ImG and IgG antibody responses in serum.

PMID- 8548538
TI  - Characteristics and clinical significance of a stabilization assay to detect
      specific antibodies to reverse transcriptase of human immunodeficiency virus.
AB  - Antibodies against reverse transcriptase (RT) of human immunodeficiency virus
      type 1 (HIV-1) have been detected in seropositive subjects by
      immunoprecipitation, Western immunoblotting, and neutralization assay. Recently,
      we noticed that the antibodies against RT stabilized RT upon heat inactivation,
      and we have developed a stabilization assay of RT antibody. Briefly, the RT of
      HIV-1 is completely inactivated by incubation at 56 degrees C for 20 min, but
      this inactivation is inhibited in the presence of a specific antibody directed
      against this molecule. We examined the specificity and clinical significance of
      this stabilization assay. HIV-1 antibody-positive sera stabilized HIV-1 RT but
      not HIV-2 RT, whereas half of these sera cross-neutralized HIV-2 RT. Antibody
      titers against RT determined by the neutralization assay and the stabilization
      assay were compared with clinical characteristics. Antibodies against HIV-1 RT
      were much more frequently detected by the stabilization assay than by the
      neutralization assay. Statistically significant associations were found between
      stabilizing antibody titer and CD4+ cell number in peripheral blood of patients
      and also between antibody titer and CD4+/CD8+ ratios. These results indicate that
      our new stabilization assay to detect specific antibodies against RT of HIV-1 is
      useful as a clinical marker of infection and progress of the disease.

PMID- 8548539
TI  - Assignment of weight-based antibody units to a human antipneumococcal standard
      reference serum, lot 89-S.
AB  - A human reference serum pool, lot 89-S, has been developed for use in
      quantitating concentrations of antibody to Streptococcus pneumoniae. Weight-based
      units have been assigned to antibodies to 11 pneumococcal polysaccharide (PnPs)
      serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) by using enzyme-linked
      immunosorbent assay methodology and a human standard reference serum, USNRP IS
      1644. The experimentally derived assignments for anti-PnPs antibodies of the
      immunoglobulin G (IgG), IgM, and IgA isotypes in lot 89-S correlate well to the
      separately determined immunoglobulin assignment. These assignments for this
      antipneumococcal standard serum were used to quantitate IgG, IgM, and IgA isotype
      levels and the total immunoglobulin level in pediatric samples from a
      pneumococcal conjugate vaccine trial. The data indicate that these assignments
      may be used to assess levels of antibody to PnPs serotypes in human serum.

PMID- 8548540
TI  - In vitro detection of apoptotic stimuli by use of the HL-60 myeloid leukemic cell
      line.
AB  - The human histiocytic lymphoma line HL-60 has served as a model of myeloid cell
      differentiation and can be induced to differentiate along the neutrophil or
      monocytic lineage, depending on the external stimulus. The nondifferentiated cell
      line retains a premyeloid leukemic phenotype and is capable of anchorage
      independent growth and proliferation. The role of apoptosis in the regulation of
      immunologic and inflammatory events associated with homeostasis and disease has
      been most intensively studied in lymphocytes. In the present study,
      nondifferentiated HL-60 has served as a model for studying myeloid cell apoptosis
      by investigating apoptotic changes induced by camptothecin, a DNA topoisomerase
      inhibitor, as well as physiologic stimuli, including ceramide analogs and a
      monoclonal antibody against the Fas antigen. Multiparameter flow cytometry was
      used to evaluate apoptosis by measuring changes in both side scatter and
      propidium iodide staining. The appearance of apoptotic cells was confirmed
      biochemically by measuring DNA endonuclease activity by both enzyme-linked
      immunosorbent assay quantitation and DNA ladder formation on agarose gels and
      morphologically with the detection of micronuclei by confocal laser microscopy.
      These studies demonstrate that HL-60 can serve as an in vitro model for the
      detection of physiologic and pharmacologic apoptotic stimuli and for
      understanding the early and late cellular changes associated with induction of
      the apoptotic program.

PMID- 8548541
TI  - Tumor necrosis factor alpha upregulates human microglial cell production of
      interleukin-10 in vitro.
AB  - Interleukin (IL)-10 appears to play an important regulatory role in the systemic
      inflammatory response; however, production of IL-10 within the human central
      nervous system has not been described. Using cultures of human fetal microglial
      cells, the resident macrophages of the brain, we investigated the production and
      regulation of bioactive IL-10. Lipopolysaccharide stimulated acute release of
      tumor necrosis factor (TNF)-alpha (peak by 8 h) and delayed production of IL-10
      (over a 48-h period) in microglial cell cultures. Treatment of microglial cell
      cultures with TNF-alpha and IL-6 resulted in a dose-dependent release of IL-10.
      These cytokines also induced expression of IL-10 mRNA. Treatment of microglial
      cell cultures with IL-10 markedly inhibited TNF-alpha and IL-6 production. These
      findings suggest that during inflammation within the brain, acute release of TNF
      alpha and IL-6 by activated microglia could promote subsequent release of IL-10,
      which functions to minimize the potential neurotoxic effects of proinflammatory
      cytokines.

PMID- 8548542
TI  - The hook protein of Borrelia burgdorferi, encoded by the flgE gene, is
      serologically recognized in Lyme disease.
AB  - The periplasmic flagellum of Borrelia burgdorferi consists of a unipeptide
      flagellar filament, a hook, and a basal body. Here, we report the cloning and
      expression of the hook gene, flgE, of B. burgdorferi N40. The flgE gene is 1,119
      nucleotides long and is located on the 950-kb linear chromosome of B.
      burgdorferi. The primary protein sequence of FlgE shows 73% similarity to the
      FlgE protein of Treponema phagedenis and approximately 50% similarity to the FlgG
      proteins of both gram-positive and gram-negative bacteria. The flgE gene was
      cloned into an Escherichia coli expression plasmid, pMX, to produce FlgE protein.
      Subsequently, FlgE murine antiserum was prepared by immunizing mice with the
      partially purified B. burgdorferi FlgE protein. By Western blot (immunoblot)
      analysis, the antiserum was found to react with a 40-kDa peptide in the whole
      cell lysates, confirming the expression of the flgE gene in B. burgdorferi.
      Additionally, antibodies to FlgE were found in serum specimens from 19 of 42
      patients with Lyme disease. Moreover, when other antigens, including 41G (the
      immunodominant domain of flagellin), OspE, OspF, and p22, were used to test for
      the development of corresponding antibodies in these patients, 67% of these
      patients (28 of 42) reacted to at least one of these five antigens, suggesting
      that a combination of FlgE with other available B. burgdorferi recombinant
      proteins is a good candidate for substrates in assays to aid in the diagnosis of
      Lyme disease.

PMID- 8548543
TI  - Peripheral blood neutrophil responses in children with shigellosis.
AB  - Alterations in peripheral blood neutrophil function are known to occur in
      patients with colitis and may have a role in precipitating nonspecific tissue
      injury. It is not known whether neutrophil function is altered in patients with
      Shigella dysenteriae type 1 infection, during which there is extensive colitis
      and which may be associated with life-threatening complications in young
      children. Three aspects of peripheral blood neutrophil function, polarization,
      attachment to yeast particles, and locomotion, were therefore studied in 111
      children with S. dysenteriae type 1 infection and 57 children without any
      infection. All children were aged 12 to 60 months. Of the children with S.
      dysenteriae type 1 infection, 42 had leukemoid reaction, hemolytic-uremic
      syndrome, or septicemia (complicated shigellosis), while the others did not
      (uncomplicated shigellosis). Polarization and locomotion in the absence of
      chemoattractants and in response to N-formylmethionyl-leucylphenylalanine (FMLP)
      and the lipopolysaccharide (LPS) of S. dysenteriae type 1 were determined.
      Attachment to unopsonized and opsonized yeast particles was also determined.
      Children with shigellosis (uncomplicated or complicated) had more polarized
      neutrophils with and without chemoattractants than uninfected children (P <
      0.05). Children with complicated shigellosis had more polarized neutrophils with
      FMLP at 10(-7) and 10(-6) M (P < 0.05) and with LPS than children with
      uncomplicated shigellosis (P < 0.05). At 3 to 5 days after enrollment, the
      numbers of polarized neutrophils with 10(-8), 10(-6), and 10(-5) M FMLP declined
      in children with uncomplicated shigellosis but not in those with complicated
      shigellosis. Attachment to yeast particles was similar in all three groups of
      children. Locomotion was inhibited by LPS in children with shigellosis (P <
      0.05), whether it was uncomplicated or complicated, compared with locomotion in
      uninfected children. Finally, neutrophil polarization in uninfected children was
      negatively influenced by nutritional status. Thus, poorly nourished uninfected
      children had more polarized neutrophils with FMLP at 10(-9) M (P < = 0.02) and
      10(-5) M (P = 0.043) than their better-nourished counterparts. In summary,
      altered neutrophil responses are associated with both uncomplicated and
      complicated shigellosis.

PMID- 8548544
TI  - A manual bead assay for the determination of absolute CD4+ and CD8+ lymphocyte
      counts in human immunodeficiency virus-infected individuals.
AB  - CD4+ T lymphocytes are currently the most common surrogate marker indicating
      disease progression in individuals infected with human immunodeficiency virus
      (HIV). Since the cost of enumerating lymphocyte phenotypes is quite high, an
      inexpensive bead assay analyzed by light microscopy (cytosphere assay; Coulter
      Corporation, Hialeah, Fla.) was developed as an alternative method for counting
      CD4+ and CD8+ T lymphocytes. To evaluate the reliability of the cytosphere assay,
      heparinized blood was collected from 117 HIV-infected individuals and tested for
      both CD4+ and CD8+ lymphocytes by flow cytometry and the cytosphere assay. The
      Pearson correlation coefficient of the cytosphere assay compared with that of
      flow cytometry for CD4+ T lymphocytes was 0.93, with mean values +/- standard
      deviations of 534 +/- 509 by flow cytometry and 499 +/- 477 by the cytosphere
      assay. The correlation coefficient for CD8+ T lymphocytes was 0.86, with mean
      values of 831 +/- 543 by flow cytometry and 746 +/- 472 by the cytosphere assay.
      The sensitivity and specificity of the cytosphere assay in determining absolute
      CD4+ T-lymphocyte counts of less than 200/microliters were 97.6 and 94.7%,
      respectively. The positive predictive value was 90.9%, and the negative
      predictive value was 98.6%. The cytosphere assay was highly correlative to flow
      cytometry in determining CD4+ and CD8+ T-lymphocyte counts among HIV-infected
      patients. The ease and limited resources needed to perform this test make it
      ideal in developing countries and other areas where technology and finances are
      limited.

PMID- 8548545
TI  - Adenosine deaminase isoenzyme levels in patients with human T-cell lymphotropic
      virus type 1 and human immunodeficiency virus type 1 infections.
AB  - In serum, the enzyme adenosine deaminase (ADA) is known to be divided into two
      isoenzymes, ADA1 and ADA2, which have different molecular weights and kinetic
      properties. The present study investigated ADA isoenzyme levels in the sera of
      patients infected with retroviruses associated with adult T-cell leukemia (ATL),
      human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM), and
      AIDS, ADA isoenzyme activities were found to be significantly (P < 0.001) higher
      in the sera of patients with ATL, HAM, and AIDS than in the sera of healthy
      controls. In the case of the ADA subtypes in the sera of patients with ATL, ADA1
      activity was significantly (P < 0.001) elevated in patients with the acute and
      lymphoma types of ATL compared with that in patients with the chronic and
      smoldering types of ATL. ADA2 activity was significantly elevated in the sera of
      patients with the acute, lymphoma, and chronic types of ATL (P < 0.001) compared
      with that in patients with smoldering ATL and HTLV-1 carriers. In the case of
      patients with human immunodeficiency virus type 1 (HIV-1) infection, ADA1 and
      ADA2 activities in the sera of patients with AIDS and HIV-1 antibody-positive
      individuals were significantly (P < 0.001) higher than those in the sera of HIV-1
      antibody-negative individuals. A significant elevation in ADA2 activity was also
      seen in the sera of AIDS patients (P < 0.01) compared with that in the sera of
      HIV-1 antibody-positive individuals. These results suggest that the magnitude of
      elevation of ADA isoenzyme levels in serum correlates well with the clinical
      conditions of the patients with these diseases. Measurement of the activities of
      ADA isoenzymes may therefore provide an additional parameter for distinguishing
      the subtypes of ATL and may prove to be useful as prognostic and therapeutic
      monitors in diseases associated with HTLV-1 and HIV-1 infections.

PMID- 8548546
TI  - Evaluation of two recombinant Maedi-visna virus proteins for use in an enzyme
      linked immunosorbent assay for the detection of serum antibodies to ovine
      lentiviruses.
AB  - Defined segments of the gag polyprotein and transmembrane envelope glycoprotein
      from Maedi-visna virus were expressed as glutathione S-transferase fusion
      proteins in Escherichia coli and evaluated singly and in combination for use in
      an enzyme-linked immunosorbent assay (ELISA). Two hundred sixty field serum
      specimens from 15 sheep flocks were tested in parallel with recombinant and whole
      virus antigens, and the relative sensitivities and specificities of the
      recombinant antigens were calculated. When the recombinant gag and transmembrane
      proteins were used in combination, a sensitivity of 97.4% and a specificity of
      99.4% relative to whole-virus antigen were observed, indicating the utility of
      these proteins in diagnostic testing.

PMID- 8548548
TI  - Gene therapy for primary immunodeficiency.

PMID- 8548547
TI  - Blocking antibody assay for confirmation of urogenital Chlamydia infection.
AB  - We evaluated the Syva MicroTrak Chlamydia Blocking Antibody Assay as a
      confirmatory assay for the detection of Chlamydia trachomatis in urogenital
      specimens. During a 5-month period, 109 positives were obtained (4.9%) by the
      MicroTrak II Enzyme Immunoassay as implemented with the Syva XL automated enzyme
      immunoassay instrument. Of 98 evaluable samples, 92 (93.9%) were confirmed as
      positive by the blocking assay, and 3 blocking-negative samples had organisms
      detected by direct fluorescent-antibody analysis (blocking sensitivity, 96.8%).
      We found that direct fluorescent-antibody analysis of samples with a specimen-to
      cutoff absorbance ratio of < or = 2.0 was a reasonable confirmation alternative
      and was more cost-effective than the blocking assay.

PMID- 8548549
TI  - In vitro liposome-mediated DNA transfection of epithelial cell lines using the
      cationic liposome DC-Chol/DOPE.
AB  - Clinical trials using cationic liposome-mediated DNA transfer have now been
      initiated for several disorders including cystic fibrosis. Previous studies have
      shown that the level of gene expression achieved may be dependent on the
      formulation of the DNA-liposome complex and the cell type transfected. We have
      investigated, in vitro, the effect of parameters such as DNA:liposome ratio, dose
      and concentration on the level of transgene expression in epithelial cell lines
      using the cationic liposome DC-Chol/1,2-dioleoyl phosphatidylethanolamine (DOPE).
      A narrow range of conditions was found to produce maximal level of transgene
      expression within a particular cell line, as detected using the reporter molecule
      beta-galactosidase (beta-gal). beta-Gal expression was significantly enhanced by
      formulation of the DNA-DC-Chol/DOPE complexes in physiological solution at pH
      9.0. Under standard in vitro transfection conditions, increased incubation time
      of the DNA-liposome complexes with cells resulted in increased transgene
      expression. In contrast, at relatively high DNA and liposome dose and
      concentrations, beta-gal activity was maximal after only 1 h of incubation, with
      a subsequent decrease in expression with time. The maximum level of expression
      that could be produced using fully optimised transfection conditions, however,
      was still highly dependent on each cell type analysed. Correlation of these
      findings with similar studies in vivo are now critical to determine the optimal
      formulation of DNA-liposome complexes for clinical application.

PMID- 8548550
TI  - Evaluation in vitro and in vivo of cationic liposome-expression construct
      complexes for cystic fibrosis gene therapy.
AB  - We have tested the cationic liposome N-(1-(2,3-dioleoyloxy)propyl)-N,N,N
      trimethyl-ammoniummethylsul phate, (DOTAP), for gene delivery in vitro and in
      vivo with a view to clinical use in gene therapy for cystic fibrosis. Delivery of
      lacZ cDNA-DOTAP complexes via aerosol showed promoter-dependent differences in
      the pattern and longevity of expression. Repeated administration was well
      tolerated. The potential for the transfer of foreign genes into reproductive
      tissue was investigated by intravenous injection of DNA-DOTAP into female mice.
      Foreign DNA was undetectable in the ovaries by Southern blot analysis at 1 and 7
      days after injection. Our results suggest that DOTAP merits testing in cystic
      fibrosis patients for delivery of the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene to the respiratory tract and that substitution of the
      cytomegalovirus (CMV) promoter for the simian virus (SV) promoter may improve on
      the transitory response reported previously.

PMID- 8548551
TI  - Alveolar stem cell transduction by an adeno-associated viral vector.
AB  - In inherited disorders such as surfactant protein deficiencies or cystic fibrosis
      (CF), where lung damage develops progressively after birth, gene replacement is
      best accomplished in the neonatal period. We use the adeno-associated virus (AAV)
      as a vector for gene transfer in the newborn rabbit lung where stem cells are
      activated for lung growth and differentiation. AAV-mediated gene transfer as
      assayed by lacZ gene expression occurred preferentially in alveoli in the
      alveolar epithelial progenitor cell, the type II cell, and in the large airway
      tracheobronchial basal and ciliated cells. Cell proliferation was confirmed by 5
      bromo-deoxyuridine (BRDU) labeling in regions undergoing alveolarization and
      airway branch points. Regions of cell proliferation coincided with areas of
      significant lacZ expression. Thus, dividing and differentiating cells can be
      targeted by AAVlacZ delivery to newborn lung.

PMID- 8548552
TI  - Prolonged systemic expression of human IL-1 receptor antagonist (hIL-1ra) in mice
      reconstituted with hematopoietic cells transduced with a retrovirus carrying the
      hIL-1ra cDNA.
AB  - This study was designed to test the feasibility and safety of long-term
      expression of high levels of secreted human interleukin-1 receptor antagonist
      (hIL-1ra) protein in mice by retroviral transduction of hematopoietic stem cells.
      The retroviral vector, CRIP-MFG-hIL-1ra (MFG-IRAP), carrying the hIL-1ra gene was
      used to infect mouse bone marrow (BM) which was subsequently injected into
      lethally irradiated mice. All of the mice survived and greater than 98% of the
      white blood cells (WBC) of these mice were of donor type from 2-13 months after
      transplantation. All of the mice had hIL-1ra protein in their sera (40-1200 ng of
      hIL-1ra/ml) at all assay periods for at least 15 months after transplantation.
      Bone marrow from seven of seven primary recipients produced at least one
      secondary recipient with sustained, high serum levels of hIL-1ra, indicating that
      hematopoietic stem cells had been successfully transduced. Although the hIL-1ra
      was biologically active when assayed in vitro, the mice appeared to be well and
      their WBC counts and hematocrit (HCT) were not significantly different from those
      of lethally-irradiated mice given BM cells infected with the same vector carrying
      the lacZ gene. There was also no evidence of alterations of white cell
      subpopulations. These results demonstrate that systemic production of
      biologically active hIL-1ra can be obtained by retrovirus-mediated gene transfer
      to hematopoietic stem cells and that this level of expression and secretion into
      the serum is compatible with normal BM engraftment, hematopoietic recovery and
      survival of the lethally irradiated recipient mice. These hIL-1ra-expressing mice
      represent a model to examine the functions of IL-1 and hIL-1ra and to determine
      the ability of hIL-1ra to reduce susceptibility to chronic diseases such as
      rheumatoid arthritis as well as effects of aging such as bone degeneration. The
      data further suggest that transduction and transplantation of hematopoietic stem
      cells is a potential method for delivery of hIL-1ra and other secreted
      therapeutic gene products for systemic diseases.

PMID- 8548553
TI  - Genetic instability of a MoMLV-based antisense double-copy retroviral vector
      designed for HIV-1 gene therapy.
AB  - We constructed a retroviral vector encoding a mutant tRNA(imet) gene followed by
      a HIV-1 rev-specific antisense sequence in the U3 region of the 3' long terminal
      repeat (LTR). This Moloney murine leukemia virus (MoMLV)-based double-copy
      retroviral vector was used to transduce human lymphoblastoid T-cell lines (CEM,
      Jurkat). In some clonal cell lines the expected short transcript initiated either
      from the 5' or 3' LTR tRNA-alpha rev gene was not detectable by Northern blot
      analyses of transduced, G418-resistant cells with an alpha rev-specific
      oligonucleotide probe. In other clonal cells, neither the short polymerase III
      transcript nor the full-length genomic polymerase II transcript (containing the
      3' LTR tRNA-alpha rev gene) was detectable when compared with the transduced cell
      pool. Southern blot and DNA-polymerase chain reaction (PCR) analyses specific for
      the tRNA-alpha rev cassette in the 5' or 3' LTR of the retroviral vector
      suggested that the transfer of the 3' LTR U3 region to the 5' LTR was incorrect
      in most proviruses. These data were confirmed by DNA sequence analyses of several
      clonal lines demonstrating deletions and insertions. In summary, our results
      indicate that this retroviral vector design with direct repeats flanking the
      polymerase III transcription unit plus the alpha rev insert is prone to genetic
      rearrangements and consequently not useful for the development of gene therapy
      protocols.

PMID- 8548554
TI  - Effect of cellular type on expression of acid beta-glucosidase: implications for
      gene therapy in Gaucher disease.
AB  - The effects of cellular type on the expressed activity of acid beta-glucosidase
      were evaluated using retroviral constructs containing the human cDNA. MFG
      retroviral ecotropic and amphotropic vectors containing the human acid beta
      glucosidase cDNA were produced and used to infect different murine cell lines
      (fibroblast, neuronal and monocytic) and human cells (HL60 and cord blood CD34+),
      respectively. The expression of human acid beta-glucosidase was evaluated by
      enzyme activity assays, quantitative Western blots and immunofluorescence. All
      cells permanently integrated viruses and expression of enzyme protein was
      achieved in all cell lines, but cellular transduction efficiency differed even
      between different neuronal cell lines (eg N18S > PC12). In most cell lines acid
      beta-glucosidase activity was increased between two- and three-fold with
      concomitant signal increases by Western blot and immunofluorescence N18S cells
      had poor transduction efficiency, but high cellular expression in transduced
      cells. In NIH3T3 and MC3T3-E1 cells acid beta-glucosidase protein was expressed
      in 2-, 7- and 14-day cultures after infection and at least to passage four. The
      expressed acid beta-glucosidase in NIH3T3 cells was at two to three times normal
      activity levels, and was processed similarly to the human fibroblast enzyme.
      Inactive human acid beta-glucosidase was expressed in MC3T3-E1 preosteoblastic
      cells and this was maintained during differentiation to osteoblasts. These
      results indicate that gene transfer results in cell lines may not be generally
      extrapolated to all cells in tissues or to differentiated progeny.

PMID- 8548555
TI  - Assessment of bystander effect potency produced by intratumoral implantation of
      HSVtk-expressing cells using surrogate marker secretion to monitor tumor growth
      kinetics.
AB  - A molecular marker, human alpha-1-antitrypsin (hAAT) was transduced into tumor
      cells and its secretion was found to correlate with tumor growth or regression,
      allowing for an accurate and continuous measurement of tumor growth kinetics.
      Using this system, we investigated the therapeutic potential produced purely from
      the bystander effect of HSVtk+ CT26 cells to eradicate established CT26 colon
      carcinomas in mice by direct intratumoral implantation and subsequent ganciclovir
      administration. With lower ratios (0.1% and 1% of initial tumor burden), tumor
      growth kinetics went into a static (remission) phase of approximately 2 weeks
      duration before relapse and resumption of progressive tumor growth. When the
      number of CT26tk+ modified cells injected into the tumor equaled 10% to 100% of
      the initial tumor cell number the bystander effect was sufficient to completely
      eradicate established tumors indicating that a potent bystander killing effect is
      produced in this system, and that a cellular therapy based on this approach may
      have applications.

PMID- 8548557
TI  - The 1st annual meeting of the Japanese Society of Gene Therapy. Tokyo, Japan, 21
      May 1995. Abstracts.

PMID- 8548556
TI  - Addition of a short peptide ligand to the adenovirus fiber protein.
AB  - A major concern associated with the use of recombinant adenoviral vectors is that
      viral receptors are found on the surface of many cell types and systemic in vivo
      delivery of the viral vector could result in uncontrolled and widespread
      expression of therapeutic molecules in many tissues. To construct a cell-type
      specific recombinant adenoviral vector, a new binding specificity must be added
      to the virus, and the endogenous binding specificity of the virus must be
      ablated. In order to introduce a new binding specificity to recombinant
      adenoviral vectors, the coding sequence of a physiological ligand, the terminal
      decapeptide of the gastrin releasing peptide (GRP), was placed at the 3' end of
      the coding sequence of the adenovirus type 5 fiber gene. The resulting fiber-GRP
      fusion protein was expressed using a T7 vaccinia expression system and has been
      shown to assemble protein trimers whose quaternary structure is indistinguishable
      from that of wild-type protein. The fiber-GRP fusion protein was correctly
      transported to the nucleus of HeLa cells immediately after synthesis. The added
      GRP ligand in the fiber-GRP fusion protein was accessible to binding by an anti
      GRP antibody in both the monomeric and trimeric forms of the chimeric protein.
      These studies suggest that new cell type specificities for adenovirus binding
      might be introduced by genetic fusion of peptide ligands on to the carboxyl
      terminus of the adenovirus fiber protein.

PMID- 8548558
TI  - Actin.

PMID- 8548559
TI  - Redistribution and fate of colchicine-induced alkaline phosphatase in rat
      hepatocytes: possible formation of autophagosomes whose membrane is derived from
      excess plasma membrane.
AB  - The redistribution and fate of colchicine-induced alkaline phosphatase (ALPase)
      in rat hepatocytes were investigated by electron microscopic enzyme cytochemistry
      and biochemistry. ALPase activity markedly increased in rat hepatocytes after
      colchicine treatment (2.0 mg/kg body weight, intraperitoneal injection). At 20-24
      h after colchicine treatment, the liver showed the highest activity of ALPase.
      Thereafter, ALPase activity decreased and returned to normal levels at 48 h. In
      normal hepatocytes from control rats, ALPase activity was seen only on the bile
      canalicular membrane. However, at 20-24 h after colchicine treatment, colchicine
      induced ALPase was redistributed in the sinusoidal and lateral (basolateral)
      membranes as well as in the bile canalicular membrane. At 30-36 h after
      colchicine treatment, ALPase activity on the basolateral membrane gradually
      decreased. In contrast, ALPase in the bile canalicular membrane increased along
      with the enlargement of bile canaliculi, suggesting that ALPase in the
      basolateral membrane had been transported to the bile canalicular membrane.
      Furthermore, ALPase-positive vesicles, cisternae and autophagosome-like
      structures were frequently seen in the cytoplasm. ALPase was also positive in
      some lysosomal membranes. ALPase in hepatocytes at 48 h after colchicine
      treatment returned to almost the same location as in control hepatocytes.
      Altogether, it is suggested that excessively induced ALPase is at least partially
      retrieved by invagination of the bile canalicular membrane and then transported
      to lysosomes for degradation. In addition, this study indicates that excess
      plasma membrane might be a possible origin of autophagosomal membrane.

PMID- 8548561
TI  - Membrane-bound glycoconjugates of fetal mouse erythropoietic cells with special
      reference to phagocytosis by hepatic macrophages.
AB  - Using lectin and colloidal iron (CI) stainings in combination with neuraminidase
      digestion, glycoconjugates on the surface of erythropoietic cells of the yolk sac
      and liver in fetal mice were examined. Fetal hepatic macrophages were capable of
      distinguishing between phagocytozed and non-phagocytozed erythroid elements as
      described in our previous study. Marked differences between these two elements
      could be ultrahistochemically detected on their cell surface. The phagocytozed
      elements, such as nuclei expelled from erythroblasts and degenerating primitive
      erythroblasts, faintly bound neuraminidase-sensitive CI, and neuraminidase
      digestion imparted a weak peanut agglutinin (PNA) binding. In contrast,
      erythroblasts at various maturation stages, erythrocytes and normal primitive
      erythroblasts heavily bound neuraminidase-sensitive CI, and neuraminidase
      digestion imparted a moderate PNA binding. No differences in binding of either
      concanavalin agglutinin, Ricinus communis agglutinin-I or PNA were noted between
      phagocytozed and non-phagocytozed erythroid elements. Desialylation appears to be
      one of the most important signs for the recognition mechanism of fetal macrophage
      phagocytosis. During maturation of hepatic erythroblasts, sialic acid changes its
      affinity for Limax flavus agglutinin from strong to weak, and soybean agglutinin
      binding sites disappear at the basophilic erythroblast stage. Glycoconjugates on
      polychromatophilic erythroblasts acquire similar compositions to those of
      erythrocytes.

PMID- 8548560
TI  - Establishment by the rat lymph node method of epitope-defined monoclonal
      antibodies recognizing the six different alpha chains of human type IV collagen.
AB  - A group of rat monoclonal antibodies recognizing the six different alpha chains
      of human type IV collagen have been established by our novel method. The method
      is designated the rat lymph node method in which enlarged medial iliac lymph
      nodes of a rat injected with an antigen emulsion via hind footpads are used as a
      source of B cells for cell fusion to produce hybridomas. The immunogens used were
      synthetic peptides having non-consensus amino acid sequences near the carboxyl
      termini of type IV collagen alpha chains. Hybridomas were screened both by ELISA
      with synthetic peptides and by indirect immunofluorescence with cryostat sections
      of human kidneys. Because the epitopes of all antibodies were determined by
      multipin-peptide scanning, they were confirmed to be isoform-specific. They are
      useful for identification of alpha chains of type IV collagen at the protein
      level in normal and abnormal conditions. The combined use of synthetic peptides
      as immunogens, the rat lymph node method as making monoclonal antibodies, and the
      multipin-peptide scanning as epitope mapping is found to be a strong tool for
      identification of peptides and proteins whose amino acid sequences are known or
      have been deduced.

PMID- 8548562
TI  - CCAAT/enhancer-binding protein (C/EBP) immunoreactivity during rat liver
      carcinogenesis.
AB  - To elucidate cell differentiation in liver carcinogenesis, we have studied the
      CCAAT/enhancer-binding protein (C/EBP). C/EBP is a positive-acting transcription
      factor important for the maintenance of liver-specific functions. It is
      associated with differentiation and regarded as an anti-proliferative agent. We
      have studied the expression and localization of C/EBP during sequential rat liver
      carcinogenesis. Two-color immunohistochemistry and confocal laser scan microscopy
      demonstrated C/EBP in hepatocyte nuclei and preneoplastic liver lesions, but not
      in bile ducts, non-parenchymal cells or oval cells. Both western blotting and
      immunohistochemistry revealed down-regulation of C/EBP during normal regeneration
      and when regeneration was inhibited by the carcinogen, 2-acetylaminofluorene. A
      similar down-regulation was shown by western blotting in hepatocytes grown in
      culture. Our data suggest that the altered metabolic phenotype of preneoplastic
      liver lesions was not caused by a change in the expression of C/EBP. Furthermore,
      the data favor a hepatocyte derivation of preneoplastic liver lesions.

PMID- 8548563
TI  - Hypercholesterolemia increases manganese superoxide dismutase immunoreactive
      macrophages in myocardium.
AB  - The effect of hypercholesterolemia on manganese superoxide dismutase (MnSOD)
      containing macrophages was investigated in male New Zealand white rabbits.
      Macrophages from control animals, which were marked with the RAM-11 antibody,
      demonstrated co-localization with MnSOD immunoreactivity, e.g. in the peri- and
      paravascular space within the myocardium, but not in the bone marrow. In rabbits
      fed a 0.5% cholesterol-enriched diet for 42 days, a significant increase (P <
      0.01) of MnSOD-immunoreactive macrophages within the myocardium was found
      concomitant to the drastic elevation of serum cholesterol level. In the bone
      marrow, MnSOD immunoreactivity did not change after cholesterol feeding. Thus in
      cholesterol-fed rabbits, the increase of MnSOD-containing macrophages seems to
      parallel that of lipoproteins. MnSOD is considered as being protective against
      the cytotoxic effects of those superoxide anions, possibly generated in
      macrophages, which are involved in the metabolism of modified lipoproteins.

PMID- 8548564
TI  - Zone-specific localization of cytochrome P45011B1 in human adrenal tissue by PCR
      derived riboprobes.
AB  - Cytochrome P45011B1 (11 beta-hydroxylase) was detected in the human adrenal
      cortex and in human adenomas by in situ hybridization methods. Specific
      riboprobes were generated by in vitro transcription of 11 beta-hydroxylase-
      specific synthetic oligonucleotides with attached T7 and SP6 polymerase
      promotors. [35S]- and digoxigenin-labeled riboprobes were hybridized to sections
      of an aldosterone-producing adenoma (APA), the non-tumour portion of the
      corresponding adrenal gland, and two adenomas not related to hyperaldosteronism
      using standard protocols and varying washing conditions. After exposure of the
      radiolabeled sections to X-ray film, the signals were quantified and compared by
      statistical tests. Following autoradiography or immunohistochemical detection of
      the digoxigenin cytochrome P45011B1 mRNA was clearly localized in the zona
      fasciculata/reticularis of non-tumour portion of an human adrenal with an APA.
      Zona glomerulosa, medulla and connective tissue were free of label. As revealed
      by the semi-quantitative analysis, 11 beta-hydroxylase mRNA signals in the APA
      were significantly lower than those in the attached non-tumour portion and the
      other two adenomas. The results confirm known observations on the occurrence of
      cytochrome P45011B1 in the adrenal cortex of other species, but show, contrary to
      several immunohistochemical studies, that the enzyme is obviously not expressed
      in the zona glomerulosa.

PMID- 8548565
TI  - Monoclonal antibody against the glutaraldehyde-conjugated polyamine, spermine.
AB  - We developed a mouse monoclonal antibody (ASPM-29, mAb) against spermine (Spm)
      conjugated to human serum albumin (HSA) using glutaraldehyde-sodium borohydride,
      for applications in immunocytochemistry (ICC). The antibody specificity was
      evaluated by an enzyme-linked immunosorbent assay (ELISA) binding test,
      simulating the ICC of tissue sections. ASPM-29 showed an almost equal
      immunoreactivity to Spm and spermidine (Spd) but no reactivity to any of the
      other polyamine (PA)-related compounds tested. By use of this antibody, indirect
      immunoperoxidase staining was observed in different tissues fixed with
      glutaraldehyde in combination with borohydride reduction. In contrast,
      immunoreactivity was quite low in tissues fixed only with glutaraldehyde.
      Absorption controls indicated that the immunostaining could be completely
      inhibited by 50 micrograms/ml of Spm or Spd and partially inhibited by N
      acetylspermine (Ac-Spm), N1-acetylspermidine (N1-Ac-Spd), or N8-acetylspermidine
      (N8-Ac-Spd), but was hardly inhibited at all by other PA-related compounds or
      amino acids. The reactivity of the antibody with Spm conjugated on wells in an
      ELISA plate was inhibited by micromolar concentrations of Spm, Spd, Ac-Spm, N1-Ac
      Spd, or N8-Ac-Spd, in decreasing order, but not by other small molecules. Dense
      ICC staining was observed in the paranuclear and basal cytoplasm of acinar cells
      of rat pancreas, submandibular gland and paratid gland, these results being in
      complete agreement with our recent ICC methods using other mAbs produced against
      N-(gamma-male-imidobutyryloxy) succinimide-conjugated Spm.

PMID- 8548568
TI  - Applying theory to practice.

PMID- 8548566
TI  - Anti-adhesive glycosylation of fibronectin-like molecules in human placental
      matrix-type fibrinoid.
AB  - Recently, fibrinoid of the human placenta has been described as being composed of
      two main types differing in origin and chemical composition. Fibrin-type
      fibrinoid is mostly a blood clot product. Matrix-type fibrinoid was defined as
      the extracellular matrix secreted by extravillous trophoblast cells. The
      structure and composition of matrix-type fibrinoid was addressed in this study,
      focusing on fibronectins as one major constituent. A panel of antibodies directed
      against different fibronectin isoforms generated by different mRNA splicing, as
      well as antibodies recognizing oncofetal carbohydrate epitopes, were used on
      cryostat, paraffin and Lowicryl sections of placental tissue from different
      stages of pregnancy. The oncofetal carbohydrate epitopes studied comprised the
      blood group precursor antigens i and I. We identified the blood group-related
      antigen i as an additional marker for matrix-type fibrinoid. The antigen was
      detected on a glycoprotein that was also recognized by the fibronectin antibodies
      in western blots. Immunohistochemically this i-glycosylated oncofetal fibronectin
      like molecule of about 55 kDa is expressed only by the invasive phenotype of
      extravillous trophoblast. Long chain carbohydrate moieties with a structure
      fulfilling the criteria for i reactivity on human placental fibronectin are known
      to have antiadhesive properties and to enhance resistance of the protein chain to
      proteolysis. These properties underline the functional relevance of glycosylation
      of fibronectins in matrix-type fibrinoid and suggest matrix-type fibrinoid is a
      typical matrix of invasive cells. In contrast, the more mature blood group
      precursor I could be detected after sialidase pretreatment of sections. This
      antigen was expressed by villous, non-invasive trophoblast.

PMID- 8548569
TI  - Management of foot ulceration in a patient with diabetes mellitus.

PMID- 8548567
TI  - In situ lymphoproliferation in renal transplant biopsies.
AB  - A double immunohistochemical labelling procedure in paraffin-embedded renal
      tissue is reported in which CD3 was targeted as a T cell marker and Ki67 as a
      marker of cell proliferation. Proliferating and quiescent T cells were
      unequivocally identified in situ, and their precise location within the kidney
      was clarified by the use of periodic acid-Schiff counterstaining to outline the
      basement membranes. Proliferating tubular epithelial cells were also clearly
      identified. The results showed that T lymphocytes proliferate within the tubular
      compartment during acute renal allograft rejection. Preliminary evaluation of the
      method in routine transplant biopsies indicated significant correlations between
      histologically defined rejection grade and mean intratubular T lymphocytes per
      tubular cross section and between proliferation of tubular epithelial cells and
      of intratubular T lymphocytes. The associated tubular epithelial cell
      proliferation may be a response to local damage.

PMID- 8548570
TI  - The cost of wound care in the community.
AB  - As part of a project examining expenditure on all wound management materials
      currently prescribed by general practitioners in Wales, the cost of bandages and
      surgical tapes was analysed. Changes to prescribing patterns are suggested which
      could result in significant financial savings and improvements in patient care.

PMID- 8548571
TI  - Pressure sores in patients with acute spinal cord injury.
AB  - The aim of this project was to establish the extent of pressure sore development
      in patients with acute spinal cord injury. The prevalence figures over a one-year
      period from February 1993 in one ward in a spinal treatment centre were examined.
      Problems with using different classification systems and definitions are
      discussed, together with the limitations of using manual data collection and the
      difficulties of making cross comparisons between studies.

PMID- 8548572
TI  - Graduated compression hosiery for venous ulceration.

PMID- 8548573
TI  - Pressure sore prevention in a hospice.
AB  - This study investigated the influence on the number of pressure sores developing
      in patients nursed in a hospice when three levels of pressure support were used
      in association with a risk assessment tool. The study was designed as phase one
      of an epidemiological study examining the use of a modified Norton scoring
      system. This was followed by a second phase of the study, when patients were
      allocated to pressure sore support systems according to their risk assessment
      score. A total of 327 patients entered, 223 in phase one and 104 in phase two. A
      significant reduction in the development of pressure sores was observed in the
      second phase of the study.

PMID- 8548574
TI  - Review of classic research: community clinics for leg ulcers.

PMID- 8548575
TI  - Reliability of the Waterlow score.

PMID- 8548576
TI  - Classic research: moist wound healing.

PMID- 8548577
TI  - The management of venous ulcers--the medical and surgical options.
AB  - An overview, from a surgical perspective, of the treatments available for the
      most beneficial management of patients with venous ulceration of the legs.

PMID- 8548578
TI  - Methicillin-resistant Staphylococcus aureus in wound care.
AB  - A discussion detailing the development of antibiotic-resistant strains of
      Staphylococcus aureus and offering guidelines for infection control procedures.

PMID- 8548579
TI  - Regulation of retinoblastoma gene expression in a mouse mammary tumor model.
AB  - We initiated studies to investigate the involvement of the murine retinoblastoma
      (RB) gene in mammary carcinogenesis using cell lines derived from mammary glands
      of irradiated mice. We found that the RB mRNA levels as well as the amounts of
      the nuclear phosphoprotein were significantly reduced as the cells progressed in
      vitro from non-tumorigenic to tumorigenic stages. To further investigate RB gene
      expression with cellular development and tumorigenicity, we transfected malignant
      cells with expression vectors containing the murine RB cDNA driven by either the
      SV40 or the mouse metallothionein promoter sequences. The neomycin resistant gene
      was included in both vectors and was used as a selective marker for the
      transfected cells. Cells with reduced levels of endogenous RB mRNA were stably
      transfected and showed increased expression of RB. In addition, the morphology of
      these cells were altered and their growth rates in culture were reduced.
      Injection of the transfected cells into host mice resulted in a delayed onset of
      tumors compared with nontransfected parental cells. Our studies provide
      experimental data to confirm that loss of RB gene activity is involved in
      neoplastic transformation of cells and support the multistep theory of
      carcinogenesis.

PMID- 8548580
TI  - Effectiveness of three ribozymes for cleavage of an RNA transcript from human
      papillomavirus type 18.
AB  - We tested three hammerhead ribozymes for their ability to bind and cleave RNA
      transcripts derived from the E6 and E7 genes of human papillomavirus (HPV) type
      18. Targets were located at nucleotides (nt) 123, 309, and 671 of the viral
      transcript. In vitro each ribozyme hybridized to its target site when the
      ribozyme:target ratio was 20:1 or greater and achieved maximal hybridization
      within 1 hour. HPV RNA from the HeLa cervical cancer cell line was cleaved
      effectively by each ribozyme. When HPV RNA and a ribozyme were expressed
      simultaneously in Escherichia coli, each ribozyme produced a significant
      reduction in the intracellular concentration of HPV RNA. In each assay the
      ribozyme directed to nt 309 was the most effective. A noncatalytic antisense
      molecule was used as a control and did not digest HPV RNA or reduce its
      concentration. The data imply that three different ribozymes each have potential
      for use in gene therapy of human tumors that express HPV-18 but that the ribozyme
      targeted to nt 309 is likely to be most effective.

PMID- 8548581
TI  - An improved retroviral vector encoding the herpes simplex virus thymidine kinase
      gene increases antitumor efficacy in vivo.
AB  - Brain tumors have been treated clinically by intratumoral injection of cells that
      produce retroviral vectors encoding the herpes simplex virus thymidine kinase
      (HSV-TK) gene followed by systemic administration of the antiviral drug
      ganciclovir. In vitro and in vivo comparisons of two different HSV-TK vector
      producer clones, which were made using standard transfection and transinfection
      techniques, were conducted. The two clones, PA317/G1TkSvNa.53 (TK.53) and
      PA317/G1Tk1SvNa.7 (TK1.7), both used in clinical trials, differ with respect to
      sequences 3' to the HSV-TK stop codon. The retroviral construct used to generate
      the TK.53 vector producer cell clone contains an open reading frame encoding a
      portion of the herpes simplex virus glycoprotein H (gH), a potential
      polyadenylation site and a putative splice site in this region. These sequences
      were removed from the retroviral construct used to create the TK1.7 vector
      producer cell clone. Supernatants obtained from TK1.7 vector producer cells had
      100- to 1000-fold higher titers (G418 or HAT) than did corresponding supernatants
      from TK.53 vector producer cells. A murine subcutaneous tumor model was used to
      assess transduction efficiency and antitumor activity of each vector producer
      cell clone. In vivo tumor cell transduction was 13- to 18-fold more efficient
      with TK1.7 cells as compared with TK.53 cells at equivalent doses. Complete tumor
      ablation was achieved using a 10-fold lower dose of TK1.7 cells as compared with
      TK.53 cells. These results suggest that TK1.7 cells combined with ganciclovir may
      provide a more potent antitumor response in humans.

PMID- 8548582
TI  - A novel nonviral cytoplasmic gene expression system and its implications in
      cancer gene therapy.
AB  - We recently have developed a unique cytoplasmic transient gene expression system
      based on cotransfection of target cells with bacteriophage T7 RNA polymerase
      (RNAP) and plasmid DNA vectors containing a T7 autogene. Because this T7 system
      is self-initiating, self-maintaining, and requires no cellular factors for
      transcription, it is therefore likely to function in any mammalian cell with any
      gene both in vitro and, more importantly, in vivo. In this study we demonstrate
      that the T7 DNA vector and T7 RNAP could be efficiently codelivered to cultured
      cells by lipofection. Different target genes were expressed by the T7 system in a
      wide variety of mammalian cells including several tumor cell lines. Gene
      expression could be detected in more than 30% of the cells of some tumor cell
      lines transiently transfected by the T7 vector. Average activity of the reporter
      enzyme (luciferase) expressed by a transfected cell was relatively constant
      regardless of the cell line used. When a T7-luciferase vector was directly
      injected into various tissues of mice without the use of liposomes, luciferase
      activity could be found in the injected liver, muscle, brain and tail connective
      tissues. The luciferase levels expressed by the T7 system were found to be up to
      200-fold higher, depending upon the injected tissues, than levels achieved with a
      traditional nuclear gene expression vector. Direct tumor injection with a T7-beta
      galactosidase (beta-gal) construct resulted in beta-gal gene expression in tumor
      cells near the injection sites. In addition, direct injection of the T7 system in
      mice did not generate detectable quantities of antibodies against the T7 RNAP.
      These results suggest that this gene expression system may be useful in many
      different medical applications such as cancer gene therapies and DNA vaccination,
      where transient but rapid and efficient gene expression is required.

PMID- 8548584
TI  - [Definition of chronic inflammatory bowel disease. Conceptual evolution].

PMID- 8548583
TI  - Vectors in cancer therapy: how will they deliver?

PMID- 8548586
TI  - Smoking and inflammatory bowel disease.

PMID- 8548585
TI  - [Methodological considerations on the epidemiology of chronic inflammatory bowel
      disease].

PMID- 8548587
TI  - [Characteristics of lymphocyte populations and macrophages of the lamina propria
      in chronic inflammatory bowel disease. The role of cytokines].

PMID- 8548588
TI  - [Polyunsaturated fatty acids and their metabolites in chronic inflammatory bowel
      disease].

PMID- 8548589
TI  - [Role of reactive oxygen metabolites in the pathogenesis of chronic inflammatory
      bowel disease].

PMID- 8548590
TI  - The validity of intraoperative frozen section diagnosis based on video-microscopy
      (telepathology).
AB  - The validity of intraoperative frozen section diagnosis (IFSD) via telepathology
      between Hokkaido University School of Medicine (HUSM) and a remote hospital was
      evaluated. Video-microscopic images of hematoxylin-eosin (HE)-stained frozen
      sections were transmitted by a cytoscreener via the Pathtran 1,000 system and a
      telephone line to a color monitor at HUSM (120 km from the submitting hospital)
      with a resolution of 512 x 480 pixel matrix. The pathologists at HUSM made
      diagnoses on the received images. Of the 59 cases, there was diagnostic
      concordance between telepathology and permanent paraffin sections in 19
      malignant, 36 benign, and one borderline case. The latter was a case of atypical
      ductal hyperplasia of the breast. The telepathology diagnostic modality was
      inconclusive in three cases, two of which were benign and one malignant by
      paraffin section examination. These results provide evidence for the diagnostic
      adequacy of video-microscopic images, the interpretation of which compared
      favorably with that of conventional frozen sections. Although the need for IFSD
      is increasing, the proportion of hospital pathologists accepting this modality is
      not. For the appropriate use of telepathology, it is necessary that more
      pertinent personnel, especially cytoscreeners and pathologists receive a thorough
      training and become familiar with the system. Telepathology offers pathologists a
      diagnostic modality that responds to the needs of physicians and serves to
      enhance the pathologist's position in health care services.

PMID- 8548591
TI  - Expression of tenascin in tumors of the esophagus, small intestine and
      colorectum. An immunohistochemical study.
AB  - Tenascin, a large glycoprotein of the extracellular matrix, is involved in cell
      proliferation, differentiation, and migration during embryogenesis. In adult
      tissue, it is expressed only in certain areas. However, it gains importance again
      in proliferative processes such as wound healing and especially in tumor
      development. We examined paraffin-embedded specimens of 25 patients with a
      squamous cell carcinoma of the esophagus, 5 patients with an adenocarcinoma of
      the small intestine, 4 patients with a carcinoid tumor of the small intestine,
      and 49 patients with an adenocarcinoma of the colorectum. Immunohistochemical
      staining was performed by the use of a monoclonal antibody against human tenascin
      and the avidin-biotin-complex technique. Amino-Ethylcarbazol served as a
      chromogen. We investigated the distribution of tenascin in tumors, normal tissue,
      and lymph node metastases and compared it to tumor grading and TNM
      classification. We found a uniform pattern of tenascin expression in all tumors
      and lymph node metastases examined in the gastrointestinal tract. One pattern was
      characterized by an immunoreaction near the basement membrane in well
      differentiated areas and the other showed a diffuse, network-like expression in
      poorly differentiated areas with abundant stroma. There was a more intensive
      staining of the surrounding stroma near tumor cells invading into the submucosa
      or muscularis propria. It was even possible to detect small early carcinomas as
      well as small tumor cell populations in and around the lymph nodes by a strong
      immunostaining of the surrounding stroma. But we could not find any correlation
      of the tenascin expression patterns in comparison to the tumor grading and TNM
      classification.

PMID- 8548592
TI  - A comparative study of nuclear morphometry and proliferating activity in
      neuroectodermal tumors of bone and Ewing's sarcoma of bone.
AB  - A neuroectodermal tumor of bone (NTB) is a small round cell tumor with Homer
      Wright rosettes. The differences in the nuclear profiles, proliferating
      activities, and biologic behavior between NTB and Ewing's sarcoma of bone (ESB)
      are still controversial. In this study, 11 cases of NTB and 12 cases of ESB were
      compared by a nuclear morphometrical approach using an image analyzer. In
      addition, the proliferative activity was also evaluated between the two groups by
      an immunohistochemical study using proliferating cell nuclear antigen (PCNA). The
      nuclei of NTB were found to be significantly more elliptical (Form Ell: NTB =
      0.725, ESB = 0.743, P = 0.017) and irregular (Form Ar: NTB = 0.908, ESB = 0.933,
      P = 0.046) than those of ESB. The maximum diameter of the nuclei in NTB was
      larger than those of ESB (NTB = 6.92 micron, ESB = 6.33 micron, P = 0.017),
      however, there were no significant differences in the nuclear area between the
      two groups. Immunohistochemically, the mean PCNA score of the NTB (10 cases) were
      significantly higher than those of ESB (7 cases) (NTB = 25.9, ESB = 11.6, P =
      0.005). The mitotic activities of NTB (17/10HPF) were also higher than ESB
      (6/10HPF) (P = 0.0008). There were no significant differences between the two
      groups in survival (log-rank test: P = 0.324) according to our small series. Our
      results suggest that these two tumors should be separated because their
      proliferating activity is different and they can be separated by some nuclear
      profiles.

PMID- 8548593
TI  - Proliferative activity and p53 over-expression of ovarian epithelial tumors.
AB  - Proliferative activity (PA) and p53 over-expression were assessed in 68 cases of
      primary ovarian epithelial tumors of variable grades of malignancy by
      immunohistochemical methods using antibodies to PCNA (proliferative cell nuclear
      antigen) and p53 molecule. First, we compared the values in benign tumors, tumors
      of borderline malignancy and malignant tumors. Malignant tumors possessed higher
      PA value (26.8 +/- 14.7%) than benign tumors (1.6 +/- 1.4%), and tumors of
      borderline malignancy exhibited an intermediate value (11.4 +/- 5.1%).
      Intranuclear accumulations of p53 product were more frequently observed in
      malignant tumors (16/32, 50%) than in tumors of borderline malignancy (3/9, 33%).
      None of the benign tumors exhibited p53 over-expression. In malignant tumors, PA
      correlated well with the histologic grade of tumors, although the histologic type
      and stage of the diseases did not correlate significantly with PA. Then, we
      focussed on the cases of malignant ovarian cancer composed of heterogeneous
      lesions showing a different grade of malignancy; invasive lesion (IL), non
      invasive lesion (NIL), and benign appearing lesion (BAL). PA of NIL was almost
      identical with that of IL (19.6 +/- 13.5% vs. 23.3 +/- 12.6%), while BAL showed
      significantly lower PA (2.1 +/- 3.0%, p < 0.001) than the above two lesions and
      was similar to that of benign tumors. Furthermore, p53 over-expression was never
      observed in BAL, even in cases in which IL and/or NIL showed p53 over-expression.
      Thus, the results indicated that histologically benign-appearing lesions of
      malignant ovarian epithelial tumors possessed a biologic character similar to
      benign tumors. Collectively, all these findings would support the concept that a
      part of malignant ovarian epithelial tumors would be derived from benign tumors
      through progressive transformation.

PMID- 8548594
TI  - Lectin binding sites and immunocytochemical characterization of normal pleural
      mesothelium.
AB  - 20 specimens of normal pleural mesothelium were investigated with six lectins
      using isolated cells and tissue specimens as well as two different fixation
      techniques (glutaraldehyde and formaldehyde) and 10 monoclonal antibodies (MAb)
      on cytologic preparations only. Lectin binding sites for ConA, WGA, and PNA were
      present in all cases, whereas binding sites for the lectins HPA, SBA, and UEA-I
      could never be found. There was no staining difference with the two preparation
      and fixation techniques proving that they may be used to compare directly
      histologic and cytologic studies. Ten of fourteen histologic specimens were
      positive for the blood group antigen Lewis(y), three of them were positive for
      the antigen Lewis(b), all fourteen specimens were negative for Lewis(a) and
      Lewis(x). In all cases, mesothelial cells expressed ICAM1 and pancytokeratin. The
      antibodies against EMA, CEA, CD24, CD15, CD20, CD5, and HEA125 showed no reaction
      in mesothelial cells. Because HPA, UEA-I, SBA as well as CEA and HEA125 react in
      a high percentage with adenocarcinomas, non reactive cells of pleural effusions
      negative with these markers may be confidentially considered to be mesothelial in
      origin.

PMID- 8548595
TI  - Massive intestinal hemorrhage associated with intestinal amyloidosis. An
      investigation of underlying pathologic processes.
AB  - Two cases of systemic amyloidosis with massive intestinal hemorrhage
      necessitating bowel resection prompted an investigation of the possible
      pathologic processes leading to such hemorrhage, since no conclusive information
      about this has been published. METHODS: The two surgical specimens and, for
      comparison, one biopsy specimen and autopsy specimens from six cases of
      amyloidosis were investigated by various histologic techniques. RESULTS: Massive
      amyloid deposition in the muscularis mucosae was noted in both surgical
      specimens. The source of hemorrhage was identified as being located at the border
      between the muscularis mucosae and the overlying rectal or colonic mucosa. In the
      autopsy specimens, there was patchy or linear amyloid deposition in the
      muscularis mucosae, but no hemorrhage. CONCLUSIONS: Various factors could be
      involved in causing massive intestinal hemorrhage in systemic amyloidosis.
      Functional disturbances may be involved due to amyloid deposition in relation to
      blood vessels, lymphatics, nerves, and nerve plexuses, and, as it appeared to be
      the case in the two surgical specimens investigated, massive deposition in the
      muscularis mucosae. The reduced motility and increased rigidity of the
      musculature probably result in shearing forces being set up in the presence of
      mechanical strain (eg in coprostasis or colonoscopy) that lead to tears in the
      region of the muscularis mucosae and to massive hemorrhage. Intestinal hemorrhage
      in amyloidosis may also be related to disturbances of coagulation, which have
      been reported in occasional cases, and ulceration, probably resulting in some
      cases of ischemic colitis.

PMID- 8548596
TI  - Congenital myopathy with focal loss of cross striations: a case report with
      morphologic and immunohistochemical study.
AB  - A case of an unusual congenital myopathy is reported. The boy presented at birth
      with generalized muscular hypotonia and dysmorphic features. Muscle biopsy at the
      age of 10 years revealed focal areas with decreased ATPase activity and variable
      oxidative enzyme activity. There was only one type II fiber in the whole section.
      22.5% of fibers had central nuclei, sometimes with radial arrangement of the
      intermyofibrillary network. Focal lesions displayed strong desmin and weak
      vimentin immunoreactivity. On electron microscopic examination normal sarcomeres
      were focally disrupted and mitochondria were absent from these areas; the normal
      structure was replaced by numerous fragments of sarcoplasmic reticulum,
      filamentous material, scattered glycogen particles, and the Z-line was replaced
      by irregular longitudinal streaks of electron-dense fibrillar material. We
      classify this case as a congenital myopathy with focal loss of cross striations.

PMID- 8548597
TI  - Extra-abdominal aggressive fibromatosis after treatment of a Morbus Hodgkin. A
      case report.
AB  - The proliferations of the connective tissue, which are summed up under the term
      fibromatoses, assume a special position with regard to their biologic behavior.
      While superficial fibromatoses are more likely to grow slowly, musculoaponeurotic
      fibromatoses (Desmoid tumor)--like malignant tumors--show a locally bound
      aggressive, rapid growth behavior. A metastazation, however, can never be proved.
      The research on etiology of fibromatoses has yielded only little knowledge.
      Besides genetic and hormonal factors, physical reasons are under discussion, too.
      The present study aims to add another description of a case report to the small
      number of case presentations on radiotherapy-associated fibromatosis. In 1977, a
      now 67-old-patient was irradiated because of a Morbus Hodgkin lymphoma in the
      left side of his neck. Prior to the radiation, the patient had undergone several
      surgeries. 17 years after the radiation, the patient developed an aggressive
      fibromatosis (prelaryngeal, right) in the formerly irradiated region. As the
      localization of the fibromatosis does not allow us to establish a connection to
      his numerous operations preceding the fibromatosis, a radiation-associated
      Desmoid tumor must be assumed. Immunohistologically, no estrogen receptors were
      detectable.

PMID- 8548598
TI  - Carcinomas of the pituitary: definition and review of the literature.
AB  - Pituitary carcinomas are defined by their disconnected mode of extension, i.e. by
      the existence of intra- or extra-cerebral metastases. Since an invasive growth in
      the sella and its neighboring regions can also be noted in many pituitary
      adenomas, this invasion cannot be counted as a criterion for malignancy. Almost
      all pituitary carcinomas stem from previously operated or irradiated invasive
      adenomas. Like adenomas, they are classified with regard to the presumable cell
      of origin and the hormone which was produced contingently. Together with 67
      pituitary carcinomas already published, three own cases are subject to a
      critical, summarizing judgement.

PMID- 8548599
TI  - Expression of cathepsin D in human astrocytic neoplasias.
AB  - The authors investigate the expression of enzyme cathepsin D in human astrocytic
      neoplasias revealing the dependency on the grade of anaplasia of the tumor. This
      investigation has shown that there is a significant difference of cathepsin D
      expression between the group of low malignant astrocytomas (G1 and G2) and the
      group of highly malignant astrocytomas (G3 and glioblastoma). Enzyme expression
      decreases when the grade of anaplasia increases. Parallel experiments have shown
      that in the investigated tumors the expression of GFAP also decreases when the
      grade of anaplasia increases. These results are related to the role of cathepsin
      D in the protein metabolism of healthy human CNS. The authors assume that in low
      malignant tumors, owing to the persisting and well-developed cytoskeleton, the
      investigated enzyme cathepsin D expresses more strongly than in highly malignant
      tumors, which are characterized by a heavier loss of their capability to express
      regular structures so that cathepsin D finds less substrate and, correspondingly,
      expresses less strongly.

PMID- 8548600
TI  - Expression of growth factors and their receptors in human osteosarcomas.
      Immunohistochemical detection of epidermal growth factor, platelet-derived growth
      factor and their receptors: its correlation with proliferating activities and p53
      expression.
AB  - The expression of both epidermal growth factor (EGF) and platelet-derived growth
      factor (PDGF), and of their receptors (EGFR and PDGFR) was immunohistochemically
      examined in 37 cases of osteosarcoma. Furthermore, immunostaining for p53 protein
      and Ki-67 antigen by MIB-1 was carried out and compared with the above results.
      EGFR (81%) expressed more often than EGF (51%) and the expression of EGF and
      EGFR, and PDGF and PDGFR were recognized in 49% and 38%, respectively. In eleven
      cases (30%), the expression of both growth factors and their receptors was
      combined. Anaplastic osteosarcoma showed higher MIB-1 index than osteoblastic and
      fibroblastic subtypes (P < 0.05). High grade osteosarcomas (G3 and G4) revealed
      higher MIB-1 index compared with low grade tumors (G1 and G2). PDGF positive
      tumors (MIB-1 index: 20.0) showed significantly higher proliferation compared
      with PDGF negative tumors (MIB-1 index: 6.5) (P < 0.01). Five out of 37 cases
      (13.5%) showed positive immunoreaction for p53. There was no correlation of p53
      status with MIB-1 index and the expression of growth factors or their receptors.
      Our results suggest that PDGF expression may be an important mediator of cell
      proliferation control, via an autocrine mechanism, in human osteosarcoma.

PMID- 8548601
TI  - [Pharmacological treatment of Alzheimer's disease: present situation and
      perspectives].
AB  - Alzheimer's disease (AD) is the commonest cause of dementia. Although its
      ethology is unknown, there is increasing evidence in support of the view that an
      abnormal degradation of the amyloid precursor protein (APP), perhaps influenced
      by a number of genetic, tisular or environmental factors, may be the primary
      cause of the many biochemical and morphological disorders that exist in the
      associative areas of the brain of these patients. Histopathologically it can be
      shown by the presence of extracellular senile plaques, intraneuronal fibrilar
      tangles and neuronal loss. There is no specific pharmacological treatment at
      present to prevent the disease or its development, in spite of the numerous and
      diverse drugs studied. Many of these studies are methodologically inadequate. The
      attempt of activating the cholinergic system has deserved special attention. A
      reversible inhibitor of acetylcholinesterase, tacrine, has been approved in the
      United States and other countries for the symptomatic treatment of mild to
      moderate AD, but its use still arises many questions. Different drug and non drug
      related interventions may be of great value in the care of these patients, and
      may influence the specific pharmacological treatments. The complexity and
      heterogeneity of AD and the multiple factors which may take part in its evolution
      make it necessary to place special attention on the methodological aspects of the
      clinical trials with new drugs for the treatment of this disease.

PMID- 8548602
TI  - [Design of clinical trials for patients with Alzheimer's disease].

PMID- 8548603
TI  - [Clinical trials in the Alzheimer's disease: evaluation of the therapeutic
      response].
AB  - The strategy, as regards the layout of any clinical study on Alzheimer's disease
      (AD) which aspires to an evaluation of the therapeutical efficiency of a drug,
      must take as its starting point a clear specification of the criteria of
      improvement and of how such criteria are to be quantified. The measuring
      instruments of therapeutical efficiency can be divided into two main groups:
      instruments for analysing the biological parameters of the illness and
      instruments which analyse functional efficiency. Between the latter, there are
      three types of basic tools: 1. Tests which allow psychopathological clinical
      changes to be evaluated, such as a complete neuropsychological examination, an
      analysis of the global clinical impression, and a cognitive mini-test; 2.
      Psychometric tests which allow certain parameters to be quantified, such as, for
      example, the IQ co-efficient; 3. Scales which, by means of information supplied
      by care experts or by family members, allow the ability to carry out normal daily
      tasks to be quantified. The selection of the most suitable test as an instrument
      with which the criteria of improvement may be established has given rise to
      controversy and none have been found which, on their own, can fully guarantee the
      necessary requirements of objectivity, reproduceability, validity and
      homogeneity. Within these limits, the most suitable are held to be those which
      explore psychopathological changes and the data provided by an informer, together
      with the global clinical impression. The high number of tests and batteries that
      have been proposed for the evaluation of the therapeutic response indicates their
      lack of real efficiency. We would like to see the setting up of an international
      committee for the standardisation and definitive validation of the measuring
      instruments for cognitive deterioration, and thus establish--with precision,
      unanimity and a general consensus--what might be considered to be the most
      suitable criteria of improvement when evaluating therapeutic efficiency in
      Alzheimer's disease.

PMID- 8548604
TI  - [Concomitant therapies in the clinical trial in Alzheimer's disease].
AB  - Existing information has been revised regarding the accompanying medication
      (permitted medication) for patients suffering from Alzheimer's disease (AD) who
      have been treated in a clinical study. Information obtained shows a highly
      variable attitude in the various clinical studies carried out on this illness.
      This fact, together with our limited knowledge of the psychotropic effects of
      many drugs frequently used on elderly patients with Alzheimer's disease has
      resulted in the impression that there are no unanimously agreed-upon guidelines
      as regards the prescription of this type of medication. The data afforded by the
      revision suggests certain guidelines for the suitable prescription of
      accompanying medication in clinical studies of Alzheimer's disease.

PMID- 8548605
TI  - [Methodological aspects and discrepancies in the clinical trials in Alzheimer's
      disease].
AB  - Authors review the main methodological aspects concerning clinical trials in
      Alzheimer's disease, especially in those points referring to patients' selection,
      design, duration of treatment, assessment of response, concomitant treatment and
      ethical questions. Published studies in last years present important
      discrepancies in design, duration of treatment and concomitant treatments. In
      author's opinion, the optimum design for to assess the real efficacy is a double
      blind parallel design and duration of treatment should be at least one year, with
      a follow-up without treatment of at least two months. Allowed and prohibited
      concomitant treatments should be clearly specified in protocols.

PMID- 8548606
TI  - [Syndromes of continuous muscular activity: report of a central case (stiff-man)
      and a peripheral case (neuromyotonia) associated with neuroborreliosis].
AB  - We describe two cases of continuous muscular activity: one which is central (the
      stiff-man syndrome), and another which is peripheral (neuromiotony), the latter
      in a patient suffering from diabetic neuropathy and with positive Borrellia
      burgdorferi serology in the bloodstream, as well as CSF. Both cases reacted
      favourably to medical treatment. In the first case botulinic toxin was used as a
      simultaneous treatment for focal pseudodystonia in one foot. Response was good.

PMID- 8548607
TI  - [A version of alpha coma].

PMID- 8548608
TI  - [Neuroleptic malignant syndrome, multiorgan failure and peripheral
      polyneuropathy].
AB  - The Malignant Neuroleptic Syndrome (MNS) is characterised by the acute appearance
      of hyperthermia, muscular rigidity, loss of motor control, and alterations in the
      level of consciousness, which could prove fatal if not rapidly diagnosed and
      treated. It is held to be a serious idiosyncratic reaction which appears in
      patients being treated with neuroleptics, independently of the dosage and the
      length of time the drug has been prescribed. Relapses do not usually occur when
      the drug is re-prescribed, once the acute phase has been passed, which suggests
      the existence of predisposing factors. There are frequent complications (acute
      respiration difficulties, acute kidney failure, disseminated intravascular
      coagulation and multiorganic failure) which condition the prognosis. The
      treatment consists of the suppression of the neuroleptic, rehydration, and
      specific drugs (bromocryptine, sodium dantroline). We have analysed two new cases
      which reacted badly, one of them with a multiorganic failure and the other, who
      had a good initial therapeutical response but who went on to develop a peripheral
      neuropathy, an infrequent complication in international medical casebooks.

PMID- 8548609
TI  - [Mitochondrial disease due to the deficit of Q-cytochrome C oxidoreductase
      coenzyme in the respiratory chain. Report of a new case].
AB  - Reference has been made in the literature of the variability in the clinical
      presentation of deficiency of complex III of the respiratory chain, identifying
      up to the moment, four groups, the first of which is characterized by hipotonia
      and wearness starting at variable ages. We report a new case of mitochondrial
      myopathy due to deficiency of this complex and included within this first group,
      and consider the importance of defining the clinical and histochemical
      characteristics of this polymorphous entity.

PMID- 8548610
TI  - [Recurrence of meningoencephalitis induced by cotrimoxazole].
AB  - Although infrequent, one of the etiological causes of aseptic meningoencephalitis
      is drug-induced. In our patient, two cases of meningocephalitis took place over a
      period of six years, together with a meningismus following consumption of
      trimetroprim-sulphametoxazol (cotrimoxazol). Features of the cases were mental
      confusion, fever, alterations in the CSF and a benign clinical course, with a
      high degree of doubt regarding diagnosis, given the similarity of anomalies in
      the CSF to those present in partially treated bacterian meningitis.

PMID- 8548611
TI  - [Wilson disease: a new case treated with trientine].
AB  - Hepatolenticular degeneration, also known as Wilson's disease (WD), is an
      infrequent hereditary disorder which is transmitted in recessive autosomic
      fashion: its genetic defect is to be found in the long branch of chromosome 13
      (13q14.3) and allows disorder to take place which has not been sufficiently
      clarified, in the bilious excretion of the copper (Cu) which is deposited in an
      anomalous manner on a level with different organic tissues, giving rise to
      characteristic clinical manifestations which are, basically, of a neurological,
      hepatic, psychiatric and ocular nature. We present the case of a young patient
      whose case began, four years ago, with depressive-type manifestations, with
      diagnosis only being made now. Our opinion on the early detection of asymptomatic
      patients is commented on, along with that concerning the effectiveness and safety
      of therapeutic alternatives to D-penicilamine.

PMID- 8548612
TI  - [Reversible neuropsychological deterioration associated with valproate].
AB  - Valproate (VPA) is indicated for treatment of febrile convulsions (FC) and very
      infrequently is associated with impairment of cognitive functions. We present a 8
      years old girl treated with VPA for FC who manifest a dramatic behavioral and
      intellectual disorder confirmed by neuropsychological tests. Three weeks after a
      reduction of VPA dosis we observed a spectacular clinical improvement. Then,
      medication was discontinued with normalization of the neuropsychological items,
      till now, more than one year later. At all time plasmatics levels of VPA were in
      range and we never observed direct toxicity by the drug. This is an exceptional
      picture, and for our knowledge never has been reported during treatment of FC. We
      think that is important to inform of drug-induced abnormalities like this for
      avoid unnecessary exams to search for neurodegenerative disorders.

PMID- 8548614
TI  - [Type I glutaric acidity with arachnoidal cysts].
AB  - Two sisters are shown who have been diagnosed as having glutaric acidity (GA)
      type I, in the neuroimage of which bilateral arachnoidal cysts were shown. There
      is a remarkable lack of correlation between the clinical status of the patients
      and the arachnoidal cysts. The younger sister developed the first symptoms of her
      illness at around 5 years of age, whereas the cysts had already been diagnosed at
      the age of one. It was considered convenient to doubt the diagnosis of type I GA,
      given the presence of bilateral or familiar arachnoidal cysts, despite the lack
      of symptoms.

PMID- 8548613
TI  - [Complete recovery from transient coma in bilateral paramedian thalamic
      infarctions].
AB  - Bilateral paramedian thalamic infarcts (BPTI) can begin clinically with transient
      coma, after which symptoms of fluctuating hypersomnolence, irrational behaviour,
      or amnesic states may be observed. We present two patients with BPTI who began
      with coma, recovering spontaneously in under eight hours, with no accompanying
      symptoms.

PMID- 8548615
TI  - [Emotional facial paresis as a symptom of a spontaneous carotid dissection].
AB  - Emotional facial paresis consists of the absence of facial movements during
      emotional stimulus, as laughing, with a normal voluntary facial mobility. The
      anatomic ways responsible for the emotional facial mobility have been already
      studied. We present a case of emotional facial paresis caused by a striatum
      capsular infarct secondary to a spontaneous dissection of the internal carotid
      artery.

PMID- 8548616
TI  - [A young male with diffuse encephalopathy].

PMID- 8548617
TI  - [Epidemiology of cognitive deterioration in geriatric population of 'Casals d'
      Avis' in the city of Barcelona].
AB  - The aim of the study is to carry out a clinico-epidemiological study of the part
      of Barcelona's population over the age of 65 that suffers from cognitive
      deterioration, users of 'Casal d'Avis' (Old-folks centres). 369 users of 'Casals
      d'Avis' were studied. A specific questionnaire was used to collect the following
      data: personal details, social and family situation, health profile and a
      quantification of their degree of cognitive degeneration using Lobo's cognitive
      test. The quantitative and qualitative variables were studied statistically, and
      the arithmetical average and standard deviation were found, as well as which
      bivariant hypothesis tests and multivariant analyses, using the logistic
      regression method, were carried out. The degree of cognitive deterioration is
      8.67%. Age, female sex, being widowed or single, and illiteracy are associated
      with low scoring in the MEC. It is also associated with subjective loss of memory
      and hearing difficulties. The multivariant analyses are influenced by length of
      schooling, age and sex. Early detection of cognitive deterioration and the supply
      of resources and services oriented towards cognitive stimulation and social
      integration would, if well-planned, do away with the need for their confinement.

PMID- 8548618
TI  - [Epidemiology of cognitive deterioration in the institutionalized geriatric
      population of the socio-sanitary centers in the city of Barcelona].
AB  - The aim of the study is to carry out a clinico-epidemiological study of the part
      of Barcelona's in-patients of 'Health-centers/Nursing-homes' elderly people that
      suffers from cognitive deterioration. 363 in-patients of 'Health-centers/Nursing
      homes' were studied. A specific questionnaire was used to collect the following
      data: Personal details, social and family situation, health profile and
      quantification of their degree of cognitive deterioration using Lobo's cognitive
      test. The quantitative and qualitative variables were studied statistically, and
      the arithmetical average and standard deviation were found, as well as which
      bivariant hypothesis tests and multivariant analyses, using the logistic
      regression method, were carried out. Adjusted degree of cognitive deterioration
      was 56%. The age, the fact that the patients were female, illiteracy and working
      as house-wives all made for low MEC ratings. Variables such as health, subjective
      memory loss, the presence of cerebral vascular pathology an hypercholesterolemia
      behaved in a similar fashion. Age, female sex, illiteracy and being a house-wife
      are associated with low scoring in the cognitive test, as well as subjective loss
      of memory, cerebral vascular pathology and hypercholesterolemia. The multivariant
      analyses are affected by: age and length of schooling. Were the in-patient group
      is concerned, functional remodelling of specific areas is indicated, and who have
      to be taken into care as a result of the seriousness of deterioration their
      dependence and their need for assistance.

PMID- 8548619
TI  - [Temporal mesial sclerosis].

PMID- 8548620
TI  - [Transient regional osteoporosis: an enigmatic disease with a good response to
      calcitonin].

PMID- 8548622
TI  - [Meningeal infiltration as isolated recurrence of M3 type acute myelocytic
      leukemia].

PMID- 8548621
TI  - [Sexual headache and cerebral hemorrhage].

PMID- 8548623
TI  - [Brachial paralysis as a presentation of giant cell arteritis].

PMID- 8548624
TI  - [Venous sinus thrombosis as a febrile status].

PMID- 8548625
TI  - [Asymptomatic multiple sclerosis: a neuropathological study].

PMID- 8548626
TI  - [How many neurologists should work in a district hospital?].

PMID- 8548627
TI  - [How many neurologists should work in a district hospital?].

PMID- 8548628
TI  - [How many neurologists should work in a district hospital?].

PMID- 8548629
TI  - [How many neurologists should work in a district hospital?].

PMID- 8548630
TI  - [How many neurologists should work in a district hospital?].

PMID- 8548631
TI  - [Who should have a responsibility to treat cranial traumas in the hospital
      without a neurosurgery unit?].

PMID- 8548633
TI  - [Who should have the responsibility to treat head injuries in a hospital without
      a neurosurgery unit?].

PMID- 8548632
TI  - [Who should have the responsibility to treat head injuries in a hospital without
      a neurosurgery unit?].

PMID- 8548634
TI  - [Who should have the responsibility to treat patients with head injuries in a
      hospital without a neurosurgery unit?].

PMID- 8548635
TI  - [Should stroke patients be admitted into the intensive care units?].

PMID- 8548636
TI  - [A study on an early prognostic marker and multiple sclerosis].

PMID- 8548637
TI  - [General practitioners and neurology].

PMID- 8548638
TI  - [Motor units hyperactivity syndromes].

PMID- 8548639
TI  - [Preventive neuroprotection].

PMID- 8548640
TI  - [Validation of a test of neurological knowledge for general practitioners].
AB  - In order to evaluate the degree of neurological knowledge in a general
      practitioner (GP), and given the lack of a useful instrument with which to do so,
      we propose the drawing up of a neurological knowledge test which would give
      adequate psychometric guarantees. By using a broad-based sample of professionals
      working in Neurology (GPs, non-specialised paediatricians, and neurologists),
      along with sixth year medical students, and the combined work of a family doctor,
      a psychometry expert, a professor of neurology and two clinical neurologists, we
      managed to develop a multiple choice test (MCT) with 36 items that were both
      objective, valid, and reliable. This could be a useful means of evaluating the
      neurological knowledge of a GP.

PMID- 8548641
TI  - [Neurological education of general practitioners. Results of a survey carried out
      among 196 general practitioners].
AB  - We have carried out a survey among professional general practitioners in our
      province with the aim of getting to know their opinion concerning their own
      training in Neurology. The survey included questions about the adequacy of
      training, the nature of any deficiency therein (be it theoretical and/or
      practical) and ability to analyse and attend a neurological patient. The
      percentage of replies was 78% out of a total of 196 surveys. 78.8% of those
      questioned consider that their neurological training has not been sufficient
      either for clinical or general practice; while 43.8% believe that this
      insufficiency is due to a lack of practical training, 1.8% think the fault lies
      in a lack of theoretical training, and 54.32% consider that it is due to a lack
      of both practical and theorectical training. 61.2% of those questioned claim to
      have difficulties with neurological explorations, and 55.6% claim they have
      greater difficulties attending a neurological patient than other patients
      classified within other internal medical specialties. 76% consider that it is
      either partially or totally false to claim that these difficulties are
      unimportant due to the lack of treatment for neurological illnesses, although
      69.4% consider it to be partially or totally true that they will never be able to
      achieve diagnosis of a neurological patient due to a lack of the required
      complementary investigations. 43.9% consider that continued training in Neurology
      is not useful because it is a repetition of training received at university. As a
      consequence, there is an imbalance between neurological training and the need to
      attend the patient at the level of general practice, which should be set right by
      making the theoretical training given during graduation more suitable, and by
      increasing and improving practical credits.

PMID- 8548642
TI  - [Neuronal migration disorders: clinical-radiological correlation].
AB  - We present the correlation of imaging findings with clinical deficits in 34
      children with several anomalies of neuronal migration which were studied
      retrospectively. The cases studied corresponded to: Schizencephaly 10,
      lissencephaly 4, heterotopy 9, and hemimegalencephaly 2. The diagnosis of the
      malformations was performed by computerized tomography (CT) in a few patients and
      by magnetic resonance (MR) in most cases. Among the clinical alterations,
      psychomotor delay and seizures of difficult control were the most severe, both
      appeared at early age. The findings observed in this study suggest the
      correlations between extension, location and gray matter displasticity and the
      neurological manifestations.

PMID- 8548643
TI  - [Hallervorden-Spatz disease: presentation of a new case].
AB  - A case of Hallervorden-Spatz's disease is described in a thirteen-year-old
      patient, with typical case symptoms of pyramidalism, dystonia and regressive
      motor control, over the last four years. MRI provided a bilateral palidal image
      in 'tiger eye'. The possible appearance of early forms have been stressed,
      characterised by a learning delay and a regressive syndrome starting between 5-10
      years of age, along with later forms which manifest themselves mainly as
      Parkinson's disease. The MRI findings are of considerable value when diagnosing
      'in vivo'; the pathogeny is not clear, despite current theories.

PMID- 8548644
TI  - [Comparative study of nicardipine versus placebo in the prevention of cognitive
      deterioration in patients with transient ischemic attack].
AB  - The neuropsychological follow up of transient ischemic attacks can provide a
      model for evaluating the efficiency of a drug in vascular dementia. A double
      blind study has been conducted using nicardipine, a calcium-antagonist, as
      opposed to a placebo in 40 patients with transient ischemic attacks, over a six
      month period. The patients were evaluated according to a Wechsler's intelligence
      scale, and their memory was also tested before and after this period. Although no
      alterations were registered on either scale, some differences did appear in
      certain sub-tests, especially as regards the verbal coefficient. This pilot study
      has provided information concerning the possible beneficial effect of the drug,
      which should be proven by means of a larger-scale study.

PMID- 8548645
TI  - [The evaluation of the temporal lobe size by magnetic resonance in Alzheimer's
      disease].
AB  - The estimation of the size of the structures of the temporal lobe using magnetic
      resonance (MR) can be of assistance when diagnosing early degenerative dementia.
      We have carried out a survey on 17 patients with Alzheimer type dementia (ATD).
      They were classified in clinical stages according to the Reisberg global
      deterioration scale. As diagnostic criteria for ATD we used those developed by
      DSM-III-R and NINCDS-ADRDA. We carried out axial sequences of 10 mm thickness in
      protonic density and in T2, and crown sequences of 5mm in T1 perpendicular to the
      axis of the hypofield. We selected the crown incisions at the level of the
      interpeduncular cistern. We determined the areas of the temporal lobe, hypocampus
      and ventricular and two linear measurements (the interhypocampus distance and the
      maximum transverse diameter between internal layers of the craneum). The images
      were processed by means of a computer programme. The average area of both
      hypofields in patients at stages 3-5 on the Reisberg scale was 378.6 +/- 86.1 mm2
      and in stages 6-7 was of 364.7 +/- 62.2 mm2. The average area of both temporal
      lobes in patients at stages 3-5 was of 2,177.03 +/- 411.4 mm2 and in stages 6-7,
      was of 1,945.0 +/- 303.3 mm2. The shrinkage in size of the temporal lobe and the
      hypocampus in patients with Alzheimer's disease was not found to be related with
      the degree of dementia.

PMID- 8548646
TI  - [Clinical diagnosis of dementia associated with cortical Lewy bodies].
AB  - 8 cases of dementia associated with cortical Lewy bodies are dealt with, that
      were diagnosed in 1993 in examinations for dementia, using the Nottingham's
      clinical criteria. They make up 15.4% of primary degenerative dementias diagnosed
      in this examination. All developed a predominantly cortical dementia with
      variable bradiphrenia and a parkinsonian syndrome which was predominantly of the
      rigid-bradikinetic type. The dementia established itself rapidly -between 1 and 3
      weeks- in 3 cases (37.5%). 50% of patients (4 cases) showed marked psychiatric
      symptoms. In 2 cases stiffness was predominantly axial and another had
      supranuclear paralysis of vertical gaze. 3 patients had no tremor, and 2 of the 5
      remaining patients showed postural tremor. CT and axial MR images of the
      encephalon were similar to those observed in dementia of the Alzheimer type. The
      coronal MR carried out on 3 patients revealed less atrophy of the hypocampus than
      is normally observed in patients with dementia of the Alzheimer type who are at
      the same stage of development.

PMID- 8548647
TI  - [Determination of basal GH in dementias].
AB  - We have studied the plasmatic levels of the growth hormone (GH) in a control
      group consisting of 72 subjects with an average age of 69.7 +/- 8.4 years and in
      a group of 37 patients with an average age of 69.3 +/- 9.6, of which 28 were
      demented (15 with degenerative dementia and 13 with non-degenerative dementia); 8
      suffered from Parkinson's disease, and the rest showed signs of failing memory
      due to age. When comparing the plasmatic levels of GH between the patients' group
      and the control group we did not find significant differences between the
      demented and the control group, nor between the sub-groups of non-degenerative
      dementia or of those suffering from Parkinson's disease, when compared to the
      control group. However, we did find a reduction of GH that was statistically
      significant in the sub-group of degenerative dementia and the control group. This
      reduction in GH plasmatic values indicates a specific alteration in this type of
      process, which may be of certain use when searching for a hormonal marker for
      degenerative type dementia.

PMID- 8548648
TI  - [Dementias: current situation and future perspectives].
AB  - In this paper, the first one in a series of three complementary papers on
      dementias, we introduce the concept and evaluate the methods for diagnostic and
      the data provided by modern epidemiology. The current clinic criteria for the
      diagnosis of dementias are based on international instructions such as those
      included in the DSM-III-R (1987), and the ICD-10 (1992), and the criteria
      developed by the NINCDS-ADRDA or the CERAD. Such a disparity makes even more
      difficult the transcultural reliability of epidemiological information. The
      differentiation with pseudodementias, being the depressive one the most frequent
      of them (75%), the inclusion of the denominated dementia-AIDS complex, or those
      dementias related with the alcoholic illness have special relevance. In Europe
      the more solid studies proceed from the EURODEM group, and their results are
      consistent with the North American and Asiatic ones, pointing all of them out an
      exponential growing of dementia with age, which is very similar in the different
      continents. The risk factors for the Alzheimer's disease and other dementias are
      discussed and contrasted with the contributions of the different reliable
      documental sources existing.

PMID- 8548649
TI  - [Dementias: present situation and future perspectives (II). Biological markers].
AB  - In the previous paper, the first one in our trilogy about dementias, we introduce
      the concept and evaluate the diagnostic methods and the data provided by
      epidemiological investigation. In this paper we review the different biological
      diagnostic markers, based, in the first place, on the studies of neuroimage
      (computerized axial tomography, magnetic resonance, functional neuroimage
      techniques) and those properly neurophysiological; in the second place, the
      anatomopathological and physiopathological markers are examined; and, in the
      third place, those based on the modern genetic investigations. In the absence of
      an 'univocal biological marker', the current investigation about markers is on
      the way to the study of abnormal proteins discovered in the brain, of the
      modifications detected in the cellular metabolism, of the manifestations of the
      immunologic mechanisms and of the involved inflammatory processes, and is on the
      way to the advances and proximate perspectives of molecular genetics and animal
      models. Meanwhile, the diagnostic for the main dementia, due to Alzheimer's
      disease, is basically a clinic, exclusive and residual one, mainly in its initial
      stadium.

PMID- 8548650
TI  - [Dementias: present situation and future perspectives (III). Neurological,
      therapeutic, psychosocial aspects and patient care].
AB  - The lack of univocal diagnostic biological markers which are easily reproducible,
      highly specific and sensitive has propitiated the apparition of a conjunct of
      neuropsychological instruments for the detection and evaluation of dementias. The
      main markers are reviewed in this paper, the third of three papers dedicated to
      dementias by the authors. Also in the absence of a unic effective treatment for
      the Alzheimer's disease (AD), the potential pharmacological approaches pass
      through the design of methodologically correct trials which have to combine
      several drugs with palliative therapies in order to attempt to stop or delay the
      disturbance course. All that, in addition to the quick progresses obtained in
      genetics, in the neuronal transplants, in the administration of neurotrophical
      factors, in monogangliosides, in the intervention on the production of the beta
      amyloid protein or in the excitatory amino acid toxicity prevention make it
      possible to conceive realistic hopes on the discovery of a future effective
      therapy for the AD. On the other hand, a helpful surrounding for the patient
      suffering from dementia should adequately contemplate his security, stability,
      stimulation, freedom of movement and, also, the necessary environmental
      treatment. Creating units and residences specialized in dementias, home
      assistance aids, day centres, self-help groups, patients' family associations,
      the effective presence of social services which evaluate, give advice and guide
      behaviorally, and the creation of group aid programs for caretakers are necessary
      elements to improve the life quality of dementia patients and their families.

PMID- 8548651
TI  - [Alzheimer's disease].

PMID- 8548652
TI  - The second catalytic step of pre-mRNA splicing.

PMID- 8548653
TI  - A correlation between N2-dimethylguanosine presence and alternate tRNA
      conformers.
AB  - Even though the evolutionary conservation of the cloverleaf model is strongly
      suggestive of powerful constraints on the secondary structure of functional
      tRNAs, some mitochondrial tRNAs cannot be folded into this form. From the optimal
      base pairing pattern of these recalcitrant tRNAs, structural correlations between
      the length of the anticodon stem and the lengths of connector regions between the
      two helical domains, formed by the coaxial stacking of the anticodon and D-stems
      and the acceptor and T-stems, have been derived and used to scan the tRNA and
      tRNA gene database. We show here that some cytosolic tRNA gene sequences that are
      compatible with the cloverleaf model can also be folded into patterns proposed
      for the unusual mitochondrial tRNAs. Furthermore, the ability to be folded into
      these atypical structures correlates in the mature RNA sequences with the
      presence of dimethylguanosine, whose role may be to prevent the unusual
      mitochondrial tRNA pattern folding.

PMID- 8548654
TI  - Molecular dissection of the multifunctional poliovirus RNA-binding protein 3AB.
AB  - Genome replication of poliovirus, as yet unsolved, involves numerous viral
      polypeptides that arise from proteolysis of the viral polyprotein. One of these
      proteins is 3AB, an RNA-binding protein with multiple functions, that serves also
      as the precursor for the genome-linked protein VPg (= 3B). Eight clustered
      charged amino acid-to-alanine mutants in the 3AB coding region of poliovirus were
      constructed and analyzed, together with three additional single-amino acid
      exchange mutants in VPg, for viral phenotypes. All mutants expressed severe
      inhibition in RNA synthesis, but none were temperature sensitive (ts). The 3AB
      polypeptides of mutants with a lethal phenotype were overexpressed in Escherichia
      coli, purified to near homogeneity, and studied with respect to four functions:
      (1) ribonucleoprotein complex formation with 3CDpro and the 5'-terminal
      cloverleaf of the poliovirus genome; (2) binding to the genomic and negative
      sense RNA; (3) stimulation of 3CDpro cleavage; and (4) stimulation of RNA
      polymerase activity of 3Dpol. The results have allowed mapping of domains
      important for RNA binding and the formation of certain protein-protein complexes,
      and correlation of these processes with essential steps in viral genome
      replication.

PMID- 8548655
TI  - Decreasing the distance between the two conserved sequence elements of histone
      pre-messenger RNA interferes with 3' processing in vitro.
AB  - Histone mRNA 3' end formation requires the presence of two cis-acting conserved
      sequence elements: a stem-loop structure upstream from the site of cleavage and a
      purine-rich region downstream from the site of cleavage called the histone
      downstream element (HDE). Possible interactions between these two elements and
      their respective binding factors were investigated by a series of deletions (1-7
      nt) in the region between the two. The efficiency of processing decreased as the
      stem-loop and the HDE were moved closer together. In contrast with the documented
      ability of the U7 snRNP to direct cleavage at a fixed distance from the HDE in
      insertion mutants (Scharl & Steitz, 1994), all deletion substrates for which
      processing was observed were cleaved at or 1-nt upstream from the wild-type site.
      The reason for the inability of the system to cleave closer to the stem-loop
      remains unclear, but the removal of stem-loop binding protein(s) (SLBP) did not
      activate upstream cleavage events. Thus, although the processing machinery
      measures the distance between the cleavage site and the HDE of mammalian histone
      pre-mRNAs, there is a barrier limiting how far upstream cleavage can occur. These
      data allow a reevaluation of the sites of 3' end processing in known histone pre
      mRNAs.

PMID- 8548656
TI  - The polyribosomal protein bound to the 3' end of histone mRNA can function in
      histone pre-mRNA processing.
AB  - Cell cycle-regulated histone mRNAs end in a conserved 26-nt sequence that can
      form a stem-loop with a six-base stem and a four-base loop. The 3' end of histone
      mRNA has distinct functions in the nucleus and in the cytoplasm. In the nucleus
      it functions in pre-mRNA processing and transport, whereas in the cytoplasm it
      functions in translation and regulation of histone mRNA stability. The stem-loop
      binding protein (SLBP), present in both nuclei and polyribosomes, is likely the
      trans-acting factor that binds to the 3' end of mature histone mRNA and mediates
      its function. A nuclear extract that efficiently processes histone pre-mRNA was
      prepared from mouse myeloma cells. The factor(s) that bind to the 3' end of
      histone mRNA can be depleted from this extract using a biotinylated
      oligonucleotide containing the conserved stem-loop sequence. Using this depleted
      extract which is deficient in histone pre-mRNA processing, we show that SLBP
      found in polyribosomes can restore processing, suggesting that SLBP associates
      with histone pre-mRNA in the nucleus, participates in processing, and then
      accompanies the mature mRNA to the cytoplasm.

PMID- 8548657
TI  - Direct evidence that polypyrimidine tract binding protein (PTB) is essential for
      internal initiation of translation of encephalomyocarditis virus RNA.
AB  - The requirement of PTB, polypyrimidine tract binding protein, for internal
      initiation of translation has been tested using an RNA affinity column to deplete
      rabbit reticulocyte lysates of PTB. The affinity column was prepared by coupling
      CNBr-activated Sepharose with the segment of the 5'-untranslated region of
      encephalomyocarditis virus (EMCV) RNA previously shown to bind PTB. Lysates
      passed through this column were devoid of PTB, and were incapable of internal
      initiation of translation dependent on the EMCV 5'-untranslated region, while
      retaining the capacity for translation dependent on ribosome scanning. Full
      activity for internal initiation was restored by the addition of recombinant PTB
      at the physiologically relevant concentration of about 5 micrograms/mL. When
      various PTB deletion mutants were tested, it was found that this activity
      required virtually the full-length protein. Thus, PTB is an essential protein for
      internal initiation promoted by the EMCV 5'-untranslated region. However, the PTB
      depleted lysate retained the capacity for internal initiation promoted by the 5'
      untranslated regions of another cardiovirus, Theiler's murine encephalomyelitis
      virus, and of the unrelated hepatitis C virus, and in neither case did addition
      of recombinant PTB stimulate internal initiation. Therefore, PTB is not a
      universal internal initiation factor that is indispensable in every case of
      internal ribosome entry.

PMID- 8548658
TI  - Organization and complexity of minicircle-encoded guide RNAs in Trypanosoma
      cruzi.
AB  - The previously observed extensive sequence heterogeneity of the kinetoplast
      minicircle DNA in Trypanosoma cruzi, both intra- and interstrain, has raised the
      question as to how the minicircle DNA in this species can have any guide RNA
      (gRNA)-coding capacity at all, because there do not appear to be any variable
      region sequences conserved between different strains. To address this question,
      we obtained the complete edited sequence of maxicircle unidentified reading frame
      4 mRNA and identified 25 cognate gRNAs from gRNA libraries constructed from two
      clonal strains of T. cruzi--Sylvio X10/CL1 and CAN III/CL1. Libraries of PCR
      amplified minicircle-variable regions were also constructed for both strains. A
      single gene for each gRNA was identified in the same polarity within specific
      minicircle-variable regions from both strains, 60-100 nt downstream from the
      conserved 12mer sequence. GTP-capped total gRNA from one strain failed to cross
      hybridize with minicircle DNA from the other strain. The explanation for this
      proved to be the number of polymorphisms, mainly transitions, within the
      homologous gRNAs in the two strains. In most cases, these transitions did not
      destroy the edited mRNA/gRNA base pairing, as a result of the allowed G-U wobble
      base pairing. The sequences of the variable regions containing homologous gRNAs
      in the two strains probably derived from an ancestral sequence, and each has
      accumulated sufficient polymorphisms so as not to allow hybridization. Within a
      strain, multiple redundant gRNAs were identified that encode identical editing
      information but have different sequences.

PMID- 8548659
TI  - An amino-terminal polypeptide fragment of the influenza virus NS1 protein
      possesses specific RNA-binding activity and largely helical backbone structure.
AB  - The NS1 protein of influenza A virus has the unique property of binding to three
      apparently different RNAs: poly A; a stem-bulge in U6 small nuclear RNA; and
      double-stranded RNA. One of our major goals is to determine how the NS1 protein
      recognizes and binds to its several RNA targets. As the first step for conducting
      structural studies, we have succeeded in identifying a fragment of the NS1
      protein that possesses all the RNA-binding activities of the full-length protein.
      The RNA-binding fragment consists of the 73 amino-terminal amino acids of the
      protein. We have developed procedures for obtaining large amounts of the
      polypeptide in pure form. This has enabled us to establish the RNA-binding
      properties of this polypeptide and to demonstrate that it retains the ability to
      dimerize exhibited by the full-length protein. In addition, far-UV CD
      spectroscopy indicates that this RNA-binding polypeptide is largely
      (approximately 80%) helical, suggesting that the mode of dimerization of the NS1
      protein and of its interaction with RNA is mediated, at least in part, by
      helices.

PMID- 8548660
TI  - Reverse 5' caps in RNAs made in vitro by phage RNA polymerases.
AB  - We show that about one-third of the RNAs produced in vitro by viral RNA
      polymerases in the presence of m7GpppG dinucleotides have unusual 5' caps. In
      these RNAs, the initiating dinucleotide is incorporated in an orientation
      opposite to that expected so that the 7-methyl guanine (m7G) nucleotide is
      adjacent to the body of the RNA, making a "reverse" cap. The doubly methylated
      dinucleotide, m7GpppGm, containing a 2' O-methylated guanine (Gm) is incorporated
      only in the reverse orientation. Precursors of U1 snRNAs containing reverse caps
      are recognized by antibodies specific for the m7G cap structure. When injected
      into Xenopus laevis oocyte nuclei, reverse-capped pre-U1 RNAs are exported
      considerably more slowly than normal. Furthermore, U1 RNAs with reverse caps
      exhibit a striking defect in nuclear import that can be attributed to the failure
      of reverse caps to be hypermethylated to m2,2,7G caps. Thus, the presence of
      reverse-capped RNAs in RNA preparations may affect conclusions about the
      efficiency and extent of certain m7G cap-dependent processes.

PMID- 8548661
TI  - snRNA interactions at 5' and 3' splice sites monitored by photoactivated
      crosslinking in yeast spliceosomes.
AB  - Splice site recognition and catalysis of the transesterification reactions in the
      spliceosome are accompanied by a dynamic series of interactions involving
      conserved or invariant sequences in the spliceosomal snRNAs. We have used site
      specific photoactivated crosslinking in yeast spliceosomes to monitor
      interactions between snRNAs and exon sequences near the 5' and 3' splice sites.
      The last nucleotide of the 5' exon can be crosslinked to an invariant loop
      sequence in U5 SnRNA before and after 5' splice site cleavage. The first
      nucleotide of the 3' exon can also be crosslinked to the same U5 loop sequence,
      but this contact is only detectable after the first transesterification. These
      results are in close agreement with earlier data from mammalian splicing
      extracts, and they are consistent with a model in which U5 snRNA aligns the 5'
      and 3' exons for the second transesterification. After the first catalytic step
      of splicing, the first nucleotide of the 3' exon can also crosslink to nt U23 in
      U2 snRNA. This is one of a cluster of residues in U2-U6 helix I implicated by
      mutational analysis in the second catalytic step of splicing. The crosslinking
      data suggest that these residues in U2-U6 helix I are in close proximity to the
      scissile phosphodiester bond at the 3' splice site prior to the second
      transesterification. These results constitute the first biochemical evidence for
      a direct interaction between the 3' splice site and U2 snRNA.

PMID- 8548662
TI  - Clinical application of coronary angioscopic examination.
AB  - BACKGROUND: The coronary artery is examined with angioscopy in addition to
      coronary arteriogram to evaluate the potential clinical benefit of angioscopy.
      Changes in the coronary artery can be visualized which might not have been
      recognized before. METHODS: Coronary angioscopy was applied with Inoue coronary
      angioscope system, in cases with coronary artery disease. In case of angioplasty,
      a similar procedure was repeated after intervention. RESULTS: Twenty-one cases of
      coronary artery disease were examined with angioscopy. Successful visualization
      was obtained in 15 of them, with the rate to be 71.7%. The coronary angioscopy
      provided useful information about the coronary tree such as severity of
      atherosclerosis and integrity of endothelium and intraluminal thrombosis.
      Angioscopic change was even more remarkable after angioplastic intervention.
      Almost all cases had intimal abrasion. Damage to atheroma was observed in 77% of
      the cases, 38.5% had an intimal flap on dilatation site, and more thrombi were
      observed. CONCLUSIONS: Coronary angioscopic examination is valuable in the
      observation of coronary atherosclerosis and is especially helpful to evaluate
      cases of coronary angioplasty and to survey the results of therapy and severity
      of damage in the management of coronary artery stenosis.

PMID- 8548663
TI  - Prevalence of duodenal ulcer in cirrhotic patients and its relation to
      Helicobacter pylori and portal hypertension.
AB  - BACKGROUND: The prevalence of duodenal ulcer increases in cirrhotic patients.
      However, the pathogenesis remains unclear. METHODS: The prevalence of duodenal
      ulcer and their relationship to cirrhosis and portal hypertension were evaluated
      in 325 cirrhotic patients, and compared with 325 age- and sex-matched healthy
      subjects. Portal and systemic hemodynamic studies were performed in all cirrhotic
      patients. Histological examination of gastric antral mucosa for Helicobacter
      pylori (H. pylori) was performed in 16 cirrhotic patients with duodenal ulcer and
      in 34 cirrhotic patients without duodenal lesions. RESULTS: The prevalence of
      duodenal ulcer in cirrhotic patients was 9.5% (31 out of 325), significantly
      higher than 4.0% (13 out of 325) in the healthy controls (p = 0.007), but was not
      related to the severity of liver cirrhosis. The positive rate of H. pylori was
      not different between cirrhotic patients with duodenal ulcer and those without
      duodenal lesions (9/16 vs. 18/34, p > 0.05). The hepatic venous pressure gradient
      was also not different between these groups (17.2 +/- 5.1 vs. 16.1 +/- 4.9 mmHg,
      p > 0.05). Other variables including sex, smoking, and etiology of cirrhosis did
      not show significant differences. CONCLUSIONS: The prevalence of duodenal ulcer
      is significantly higher in cirrhotic patients than in the age- and sex-matched
      healthy subjects. The severity of cirrhosis, the presence of H. pylori or portal
      hypertension per se does not play an important role in the increased prevalence
      of duodenal ulcer in cirrhotic patients.

PMID- 8548664
TI  - Combination chemoimmunotherapy with interferon-alpha and cisplatin in patients
      with advanced non-small cell lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) has a relatively low response rate
      to systemic chemotherapy. Recently, several investigations have shown that
      interferon may augment the cytotoxic effect of chemotherapeutic agents and may
      improve the result of chemotherapy in treating cancers. METHODS: An open-label
      noncomparative phase II study investigated the efficacy and safety of combined
      chemoimmunotherapy for NSCLC using IFN-alpha, given by intramuscular injection
      with 9 million units thrice a week for a maximum of 26 weeks, and cisplatin by
      intravenous infusion, 100 mg/m2, every 4 weeks for a maximum of 6 cycles. Ten
      patients, with histology-confirmed NSCLC at stage IV of their diseases were
      enrolled. They included 5 men and 5 women, with an average age of 53.7 year. Five
      of them had adenocarcinoma; the other five had squamous cell carcinoma. RESULTS:
      Five patients, including two patients with squamous cell carcinoma and three with
      adenocarcinoma, obtained a partial response (response rate 50%). The time needed
      to achieve a sustained response ranged from 5 to 13 weeks with a median of 8
      weeks. The response duration ranged from 14 to 37 weeks with a median of 20
      weeks. The overall survival time for the ten patients ranged from 2 to 20 months
      with a median of 8 months. All 10 patients needed dose modifications of IFN-alpha
      and/or cisplatin because of myelosuppression and/or impaired renal function.
      Other frequently encountered side effects included gastrointestinal disturbances
      and a flu-like syndrome, but these were well tolerated. CONCLUSIONS: These
      preliminary results indicate that chemoimmunotherapy with IFN-alpha and cisplatin
      can be an effective alternative therapy for patients with advanced NSCLC, but
      there are significant side effects.

PMID- 8548665
TI  - Elevation of serum IL-6 levels in patients with acute bacterial infection.
AB  - BACKGROUND: Serum cytokine levels have been reported to elevate in acute
      bacterial infection, but the relationship of differential elevation in cytokine
      levels to patients' clinical parameters and prognosis remains controversial. The
      present study was designed to evaluate whether serum interleukin-1 alpha (IL-1
      alpha) and IL-6 levels were raised in patient with acute bacterial infection, and
      were correlated with patients clinical parameters. METHODS: Thirty patients, aged
      from 20 to 91 years, calling our emergency room with clinical evidence of acute
      bacterial infection and marked leukocytosis, were enrolled in this study. Sera
      were collected immediately and analyzed for IL-1 alpha and IL-6 levels with
      Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS: All patients with
      acute bacterial infection had measurable higher levels of serum IL-6 than normal
      volunteers. Patients with higher serum IL-6 level were more likely to have fever,
      though without statistical significance (p = 0.09). Serum IL-6 levels did not
      correlate significantly with positive blood culture result, septic shock, or
      fatal outcome. Serum IL-1 alpha levels were below minimal detectable
      concentrations in all patients checked. CONCLUSIONS: Serum IL-6 levels were
      elevated in patients with acute bacterial infection, and were possibly associated
      with the occurrence of fever. IL-1 alpha played no obvious role as systemic
      effector molecule in acute bacterial infection in our study.

PMID- 8548666
TI  - Prednisolone non-compliance and its related factors in patients with systemic
      lupus erythematosus.
AB  - BACKGROUND: The combination of western medicine and traditional Chinese medicine
      is still exerting a pervading influence on symptom relief in Chinese society. The
      Medical behavior pattern may influence medication non-compliance by patients with
      chronic illness. METHODS: The study was designed to investigate prednisolone non
      compliance and its related factors for patients with systemic lupus erythematosus
      (SLE) under giving patients' health beliefs, the influence of prednisolone and
      Chinese culture. All patients of the SLE Mutual Aid Group (N=570) participated in
      this study. A questionnaire which included medical behavior and individual
      attitudes was sent each by mail. The response rate was 63.7% (N=363); 329
      responses were useable in the study. RESULTS: Of the 329 patients, 27.9% had
      taken traditional medicine or a combination of traditional medicine with western
      medicine within the past month; 25.4% patients were non-compliant with prescribed
      prednisolone during the past week. The important reasons for non-compliance were
      feeling better, fearing side effects and treatment by Chinese medicine. The
      predicting factors for prednisolone non-compliance were the effects of the
      prednisolone, medical feasibility, patterns of medical behavior and perceived
      seriousness of the disease. Physician-patient relationship served as modifying
      factors which influenced individual attitudes toward prednisolone non-compliance
      and choice of medical behavior. Traditional beliefs, influenced by Chinese
      culture, indirectly affected prednisolone non-compliance, but through medical
      behavior patterns. CONCLUSIONS: Predisolone non-compliance is quite essential for
      SLE patients. Findings suggested that the attributes of prednisolone and the
      influences of Chinese traditional medicine should be considered as well as a
      health belief model, when trying to improve prednisolone compliance for SLE
      patients in Taiwan society.

PMID- 8548667
TI  - A 24-patient experience in hyperalimentation for acute renal insufficiency:
      emphasis on amino acid determination.
AB  - BACKGROUND: Since current quantitative and qualitative determination of amino
      acids in patients receiving hyperalimentation for acute renal insufficiency is
      not sufficient in covering many possible clinical situations encountered, a
      mathematic method was thus devised, using biochemical data, to address various
      clinical conditions. METHODS: From July 1991, all patients at the Veterans
      General Hospital-Taipei with BUN > 50 mg/dL and creatinine > 2.5 mg/dL received
      hyperalimentation according to the following principles: (1) the quantity of
      amino acid depended upon the amount of urea nitrogen appearance and urine urea
      nitrogen; (2) enriched branched-chain amino acids (at 60-70% essential amino
      acids; 30-40% non-essential amino acids) plus a glucose-base energy balance
      nutrient were used, according to the patients' metabolic state; (3) all
      parameters were checked once weekly and the data were compared by paired t-test
      just before and after one-week treatment. RESULTS: Over a 15-month period, a
      total of 24 patients were treated and evaluated. Significant reduction was found
      after treatment in nitrogen negative balance, blood urea nitrogen, urea nitrogen
      appearance or daily amino acid requirement. Serum creatinine, urine urea
      excretion power and hospital survival were slight but non-significantly improved.
      CONCLUSIONS: This quantitative and qualitative determination of amino acid can be
      cheap, easy and safe with some beneficial results. It may provide one more choice
      of treatment in renal hyperalimentation.

PMID- 8548668
TI  - The effect of acupuncture on spinal motor neuron excitability in stroke patients.
AB  - BACKGROUND: Spasticity is a common symptom in stroke patients, and its management
      constitutes a major problem in their rehabilitation. Acupuncture has been applied
      with moderate effect; their has been clinical experience but little objective
      evidence to support its use. H-reflex recovery time and H recovery curve were
      quantitative methods applied to measure spinal motor neuron excitability.
      Acupuncture for stroke patients as treatment to spastic hemiparesis was studied
      to see the acupuncture effect on increased spinal motor neuron excitability in
      spasticity. METHODS: Sixteen stroke patients with spastic hemiparesis were
      collected to evaluate the therapeutic effect of acupuncture on their spinal motor
      neuron excitability. H-reflex recovery time and H recovery curve were applied as
      quantitative evaluations of spinal motor neuron excitability. Eleven age-matched
      normal volunteers were used as a control group. RESULTS: The mean H-reflex
      recovery time of normal controls was 73.3 +/- 18.3 mesc; that of the sound-side
      limbs of stroke patients was 67.1 +/- 21.5msec. The difference was not
      significant statistically (p = 0.2). However, the mean H-reflex recovery time of
      the paretic limbs of stroke patients was 52.3 +/- 16.8 msec, significantly
      shorter than for the normal controls (p = 0.003). The mean H-reflex recovery time
      of the paretic limbs of stroke patients became 57.6 +/- 19.9 msec after
      acupuncture, significantly prolonged as compared with that before acupuncture (p
      = 0.03). The H recovery curve of the paretic limbs after acupuncture also
      approximated that of the normal controls. CONCLUSIONS: This result provides
      positive evidence of increased spinal motor neuron excitability in paretic limbs
      of stroke patients and also of the acupuncture effect which decreased that
      excitability. The study also presents a simple and practical technique for
      measuring the effects of various types of treatments, including acupuncture, on
      other types of central nervous system disorders.

PMID- 8548669
TI  - The alveolar permeability in patients with diffuse infiltrative lung disease
      detected by Tc-99m DTPA radioaerosol inhalation lung scintigraphy and the
      relationships with the pulmonary function test.
AB  - BACKGROUND: In recent years, there has been growing interest in determining the
      solute exchange across the pulmonary epithelium for various diseases. Alveolar
      permeability (AP) in patients with diffuse infiltrative lung disease (ILD) was
      investigated in an attempt to correlate it with parameters of the Pulmonary
      Function Test. METHODS: AP in 21 patients with ILD was measured by Tc-99m DTPA
      radioaerosol inhalation lung scintigraphy (DTPA). The degree of AP damage in ILD
      was presented as the slope (%/min) of the time-activity curve of the dynamic lung
      images. The AP of ILD patients was compared with the AP of 20 normal controls.
      Comprehensive pulmonary function tests, including forced expiratory volume, flow
      volume loop, and diffusion capacity by the single breath CO method, were
      performed for comparison. RESULTS: This study showed that there were (1)
      statistically significant differences among normal controls and patients with ILD
      and (2) no correlation for the slopes and parameters of pulmonary function tests.
      The patients were divided into two groups: (A) 8 ILD patients with normal chest X
      ray and (B) 13 ILD patients with abnormal chest X-ray findings. There were no
      significant differences in the results of DTPA for groups (A) and (B).
      CONCLUSIONS: When the AP of ILD patients is significantly damaged, however, the
      severity of the damage is not related to chest X-ray findings. Radionuclide
      alveolar permeability study is not related to traditional pulmonary function
      tests. The radionuclide alveolar permeability study should be used as a new
      method to evaluate lung function.

PMID- 8548670
TI  - Startle epilepsy presenting as drop attacks: a case report.
AB  - A case of startle epilepsy, induced by an unexpected touch on the left shoulder
      of a 3.5 year old boy, was investigated. The startle epilepsy manifested as an
      atonic drop attack. Neurological examination revealed a mild hemiparesis on the
      left side. Computed tomography (CT) scanning demonstrated an enhancement over the
      right parieto-frontal region, suggesting a hemangioma. Interictal
      electroencephalography (EEG) showed diffuse slowing and asymmetry of background
      activities with lower amplitude over the right centro-parieto-temporal region.
      The ictal EEG showed a paroxysmal bilaterally synchronized high amplitude single
      spike followed by a few slow waves lasting about one second over the bilateral
      centro-parieto-temporal regions. The seizure resisted anticonvulsant therapy and
      no significant responses were observed despite the use of combined therapy with
      valproic acid, phenytoin, primidone and clonazepam.

PMID- 8548671
TI  - Ischemic bowel secondary to angiocentric T-cell lymphoma of intestine: a case
      report.
AB  - A case of intestinal angiocentric T-cell lymphoma is reported, occurring in a 72
      year-old female who had suffered from poor appetite, body weight loss and
      abdominal pain for two months. Plain abdominal film revealed ileus, and she
      received laparotomy under the impression of ischemic bowel. Surprisingly,
      pathologic examination disclosed an angiocentric T-cell lymphoma of jejunum
      complicated with focal intestinal necrosis. This case emphasizes the angiocentric
      and angioinvasive character of some T-cell lymphomas. Angiocentric T-cell
      lymphoma must be considered as a possible cause of ischemic bowel.

PMID- 8548672
TI  - Scleritis in IgA nephropathy: a case report.
AB  - Scleritis may occur as an isolated phenomenon or as a manifestation of a variety
      of rheumatic diseases, infections and metabolic disorders. However, it is not
      well-known as occurring in IgA nephropathy. A 46-year-old Chinese female who
      presented with scleritis and was also diagnosed to have IgA nephropathy is
      reported. The clinical course and pathological findings of both eyes and kidneys
      are presented.

PMID- 8548673
TI  - Tc-99m MDP uptake in cerebral infarction: comparison with Tc-99m DTPA brain scan
      and Tc-99m HMPAO brain SPECT.
AB  - Intracerebral uptake of methylene diphosphonate (MDP) was unexpectedly found in
      metastatic work-up of lung cancer. The history of the 52-year-old patient
      revealed a sudden onset of weakness of right limbs 10 days ago. Technetium-99m
      diethylenetriamine pentaacetate (Tc-99m DTPA) brain scan and Tc-99m hexamethyl
      propylene amine oxime (HMPAO) brain single photon emission computed tomography
      (SPECT) were done, and both showed abnormality in the left
      temporoparietooccipital region corresponding to the territory of left middle
      cerebral artery. A repeated bone scan four months later showed complete
      resolution of the intracerebral Tc-99m MDP uptake. We present this case to
      emphasize the importance of complementary and enhanced radionuclide images.

PMID- 8548674
TI  - [Public policies and studies of opinion: working with the future].

PMID- 8548675
TI  - [The knowledge on health and the social sciences].
AB  - In this paper the main question is about the health complete interpretation. It
      is an epistemological discussion. It starts with the obstacles in the
      comprehension from several sciences (i.e. phisiology, epidemiology, and
      sociology)  about the health as a social and collective problem. The point is how
      to do the research and the conceptual interpretation. Finally, the authors
      explain theirs point of view: the most important is the nature and specificity of
      the objet health. Not view disciplinary. They show a model to understand the
      analysis of the health from the social sciences perspective.

PMID- 8548676
TI  - [The new pharmacy practice: can pharmaceutical intervention improve therapeutical
      efficiency].
AB  - BACKGROUND: The pharmaceutical activity has experienced over the last 50 years an
      important evolution in terms of concepts and contents affecting not only
      pharmacists but the whole health professionals. The subject of this study were
      the characteristics and implications of that change. METHODS: We review the main
      conditions leading to this change and characteristics of the new pharmaceutical
      activity focused mainly on the filtrate and alert about drug related problems and
      the professional intervention facing a proper resolution. RESULTS AND
      CONCLUSIONS: Some preliminary results from an investigation about the mentioned
      conditions are presented supporting the idea that this new proposed
      pharmaceutical intervention model can actually improve benefits on therapeutical
      effectiveness and save resources.

PMID- 8548677
TI  - [Tobacco and alcohol habits in a hospitalized population in a third level center.
      Region of Murcia].
AB  - BACKGROUND: The aims of this paper are twofold: to closely study tobacco and
      alcohol consumption among the adult population in the Autonomous Community of
      Murcia and to observe the relation between such habits and the morbidity of the
      population polled. METHODS: We study 1,128 patients admitted to the Virgen de la
      Arrixaca Hospital, the centre of reference in this Community, in 1992. The survey
      is done in all the hospital departments on patients and eighteen years and over.
      RESULTS: 37.4% of the persons polled are smokers, and 67.4% consume alcohol. The
      prevalence of smokers decreases with age: 57.4% of the patients aged under 30
      years are smokers, compared to 14.7% of those aged over 70 years. The prevalence
      of tobacco-related malignant tumours is 0.6% in the non-smokers, and 8.0% in the
      smokers and ex-smokers with a consumption of more than 10 cigarettes/day. The
      prevalence of malignant tumours in the digestive organs is 7.9% in patients
      consuming alcohol daily and 1.8% in non-drinkers. CONCLUSIONS: We note a decrease
      in tobacco consumption in the patient population, which is in line with the
      decrease in tobacco consumption in the general population of Spain as stated in
      the literature. Wine is the preferred drink of the study population overall, and
      beer in those aged under fifty years.

PMID- 8548678
TI  - [Cardiovascular risk factors in the fishing environment of Cartagena and
      Castellon].
AB  - BACKGROUND: To know the prevalence of the Cardiovascular Risking Factors in a
      fishing environment, with activity in the shallow-sea. METHOD: Transversal
      descriptive study spanning from December 1992 to March 1993 carried out in the
      Maritime Health Department of the Sea Social Institute, in the provincials
      administration center of Castellon and Cartagena (Murcia). And enquire has been
      done with 562 seaman belonging to the fishing profession, 346 of them being from
      Cartagena and 216 from Castellon. When they attended the compulsory medical
      checking previous to the embarking. RESULTS: An assessment of the Cardiovascular
      Risking. FACTORS: Smoking dependence, high blood pressure, hipercholesterol,
      hipertriglicedics, diabetes and obesity, depending on the origin station and the
      type of fishing net. The 65.6% and the 24.3% of the sampling are smokers and
      hipertensers respectively, and the 35.3% present figures above 240 Mgrs of
      cholesterol. Having Cartagena in caparison with Castellon higher frequencies, (p
      < 0.001) of high blood pressure and hipercholesterol. The hipertriglicedics alone
      is associated, (p < 0.01) with the different fishing modalities, being the
      trawling kind fishmen the one who to present the highest frequencies. Only the
      14.5% of the sampling is free from the so-called big risking factors and the 5.7%
      present the three of them associated (smoking dependence, hipercholesterol and
      high blood pressure). CONCLUSIONS: The high prevalence of the cardiovascular
      risking factors found, make necessary the organization of a prevention campaign
      in order to diminish the risks related to the isquimic cardiopathy and
      cerebrovascular illness, and this may be influenced by bad eating habits and
      other social an environmental factors which are common to seamen.

PMID- 8548679
TI  - [Unusual attendance at Hospital Emergency Services for asthma and chronic
      obstructive pulmonary disease and SO2 air pollution in Cartagena (Spain)].
AB  - BACKGROUND: The objective of this investigation is to determine the influence of
      air pollution (SO2 and particulate matter) on the existence of days of unusual
      attendance at emergency services for asthma and chronic obstructive pulmonary
      lung disease (COPD). A registry of attendances for these diseases and the daily
      mean concentrations of SO2 and particles were used (1989-1991). RESULTS: Unusual
      attendance days are establish by the fortnightly movable mean of the period that
      has that day as central one, under the hypothesis of a Poisson distribution with
      equal mean as the calculated one. In the logistic regression model, Odds Ratio
      (OR) between an excess of attendance of cases for asthma and SO2 levels greater
      than 80.60 m/m3 was 3.6 (CI95%: 1.1-11.7). For COPD, SO levels ten days before
      were introduced, and OR for SO2 levels more than 56.5m/m was 4.7 (CI95%: 1.5
      15.1). CONCLUSIONS: High SO2 levels are related with the appearances of days with
      an excessive use of emergencies for Asma and EPOC.

PMID- 8548680
TI  - [Utilization of medication by the elderly in Argentine].
AB  - BACKGROUND: The implementation of an information system on prescription drug plan
      that includes the pharmacological classification and the composition of the
      drugs. In addition to economic data, makes it possible to analyze prescriptions
      from a pharmacotherapeutic and economic perspective and, accordingly, carry out
      administrative and information interventions that improve the quality and reduce
      the cost of prescriptions. METHODS: The study will be conducted at the National
      Institute of Social Services for Retirees and Pensioners of Argentine (INSSJP),
      which basically covers the population aged 60 and over. The data source was the
      computerized billing of the prescriptions, used up to that time only as a
      mechanism to monitor billing; this was cross-referenced with a database in which
      the drugs were broken down into therapeutic groups and subgroups with the
      composition of the active ingredients. Beginning in 1987, a series of periodic
      monthly reports was issued on container consumption and expenditures, by
      therapeutic groups and subgroups and by the active ingredients; this was done at
      the national level and regionally, according to the INSSJP divisions. These
      reports gave rise to a series of interventions, such as the establishment of a
      drug formulary and two changes in the system of coverage that attempted to
      promote the use of single-ingredient drugs of proven efficacy. RESULTS: The 1987
      analysis of consumption revealed that the therapeutic group that accounted for
      the highest container consumption and expenditures was cardiovascular drugs (21%
      in number of containers and 32% in expenditures) and within this, cerebral and
      peripheral vasodilators represented 42% of the container consumption and 52% of
      the expenditures; antihypertensive drugs, 21% and 19%, and coronary drugs, 19%
      and 22%. The establishment of the drug formulary and the changes in the system of
      coverage caused a decline in the use of cardiovascular drugs in 1990 in terms of
      expenditures (19% and 26%); within this category, vasodilators came to represent
      27% of the container consumption and 18% of expenditures, while antihypertensive
      drugs rose to 28% and 35%, and coronary drugs to 27% and 32%. CONCLUSIONS:
      Implementation of an Information System makes it possible: a) to periodically
      evaluate the profile of prescriptions at the country and regional levels; b) to
      appropriately introduce a drug formulary and modifications in the system of
      coverage; c) to assess the consequences of the interventions carried out.

PMID- 8548681
TI  - [Activity and cost in hospitals managed by INSALUD in 1990-1993].
AB  - BACKGROUND: The improvement of the efficiency of the hospitals is a common
      objective in all the Health Systems. In the last years, different management
      measures have been implemented in the territory directly managed by Insalud,
      looking for a continuous improvement of the hospital efficiency. In this paper we
      analyze the activity and the expenses during the last four years in the Insalud
      managed hospitals. METHODS: A descriptive study of activity and costs during the
      last four years has been done in all 88 hospitals and also by groups, using usual
      indicators of intermediary products and activity and costs measured by UPAs.
      RESULTS: A global increase of activity is shown: inpatients, outpatients and
      surgery (above all ambulatory surgery) with a decrease of the average stay and an
      increase of the rotation index. The activity measured in UPAs has increased in a
      2.54% in 1993 compared to 1992 and the UPA cost in constant pesetas has been
      reduced in 688 pesetas in the same period. The different groups of hospitals are
      developing a more homogeneous behaviour regarding production indicators as well
      as costs. CONCLUSIONS: The different management measures implemented in the last
      years have produced an increase of the activity and of the expenses control
      leading to less financial increases to perform more hospital activity.

PMID- 8548682
TI  - [Quality control activities in 62 hospitals of the National Health System].
AB  - BACKGROUND: The increasing interest for quality in hospital care brought the need
      to evaluate the effect of quality control and quality assurance strategies that
      are being or could be implemented in spanish hospitals. METHODS: This article
      describes the results of the pre-assessment phase of a study carried out as a
      european concerted action in a total of 262 hospitals in 15 european countries.
      Spain contributed with 88 hospitals divided in two groups of 62 and 16 hospitals.
      The study herein reported refers to the group of 62 hospitals belonging to the
      spanish National Health System in which the characteristics of the hospital and
      the baseline situation in respect to quality assurance structures and activities
      have been assessed through the answers to the standard questionnaire used the
      study. RESULTS: Sixty-two hospitals filled out the preassessment questionnaire.
      Twenty three (37%) have a quality assurance programme and eighteen have personnel
      assigned to it. Clinical or quality control committees exist in 56 hospitals
      (90.3%). Fifty six hospitals (88.7%) know their autopsy rate, and 27 (43.5%) know
      their nosocomial infection rate as well as the adverse reactions due to blood
      transfusions. Complaints are registered in 56 hospitals (90.3%) and patients
      surveys are carried out in 54 (87.1%). Only 33 hospitals (53.2%) actually use
      this data for quality assurance purposes. CONCLUSIONS: Most of the quality
      activities in hospitals are carried out by physicians or nurses in the different
      clinical committees considered as quality committees. The patients surveys
      results and the data from patients complains are not used in those committees as
      inputs for quality actions. The committement of the top hospital management is
      needed to achieve an integrated approach to quality activities in hospitals.

PMID- 8548683
TI  - [Estimation of cost associated with incorrect surgical prophylaxis in a third
      level hospital center].
AB  - BACKGROUND: The constant increase of pharmaceutical costs is of great concern to
      the administrators of the Spanish National Health Service. Antibiotics
      administered as prophilaxis prior to surgery, play an important role in this
      increase. The compliance of physicians with protocols for chemoprophylaxis is
      therefore an important factor in the control of these pharmaceutical costs. The
      degree of compliance with the pre-established protocols of prophylaxis prior to
      surgery are examined in a tertiary level hospital during 1992 and the extra costs
      due to the lack of compliance with these protocols are estimated using a sample
      of 371 subjects. The object of this study is to describe the degree of the
      fulfillment of the protocols of surgical chemoprophylaxis in a tertiary level
      hospital and to estimate the minimum additional cost due to the wrong
      chemoprophylaxis. METHODS: A descriptive study was made of the surgical
      prophylaxis using a sample of 371 subjects. The cost was estimated from the price
      of the antibiotics administered. RESULTS: A total of 267 (71.9% IC95% = 67.3
      76.5) subjects had received incorrect prophylaxis. The most important causes of
      incorrect prophylaxis were the wrong antibiotic choice and the excessive duration
      of their administration. The incorrect prophylaxis was responsible for an
      additional cost of 1,117,287 ptas. The application of these estimates to the
      entire 1992 surgical population, at our center, would yield an estimated
      additional cost of 39,409,965 pesetas. CONCLUSIONS: Our health services would
      have substantial savings if protocols for prophylaxis prior to surgery were
      strictly followed by physicians.

PMID- 8548684
TI  - Drug resistance and biochemical characteristics of Salmonella from turkeys.
AB  - A study was conducted to determine the antibiotic resistance and biochemical
      characteristics of 2690 Salmonella strains belonging to 52 serovars and isolated
      from environmental and feed samples from 270 turkey flocks in Canada. Resistance
      of the Salmonella strains to the aminoglycoside antibiotics varied widely; none
      of the strains were resistant to amikacin, 14.2% were resistant to neomycin,
      25.8% were resistant to gentamicin, and 27.7% of the strains were resistant to
      kanamycin. Most strains (97.6%) were resistant to the aminocyclitol,
      spectinomycin. Regarding resistance to the beta-lactam antibiotics, 14.3% and
      14.4% of the strains were resistant to ampicillin and carbenicillin,
      respectively, whereas only 5 (0.2%) of the strains were resistant to cephalothin.
      None of the strains were resistant to the fluoroquinolone ciprofloxacin or to
      polymyxin B. Resistance to chloramphenicol and nitrofurantoin was found in 2.4%
      and 7% of the strains, respectively. Only 1.7% of the strains were resistant to
      the trimethoprimsulfamethoxazole combination, whereas 58.1% were resistant to
      sulfisoxazole. Thirty-eight percent of the strains were resistant to
      tetracycline. Salmonella serovars differed markedly in their drug resistance
      profiles. Biochemical characterization of the Salmonella showed that the S.
      anatum, S. saintpaul and S. reading serovars could be divided into distinct
      biotypes.

PMID- 8548686
TI  - Investigation, control and epizootiology of anthrax in a geographically isolated,
      free-roaming bison population in northern Canada.
AB  - In July 1993 anthrax caused significant mortality in an isolated, free-ranging
      population of bison (Bos bison athabascae) west of Great Slave Lake in the
      Northwest Territories. There was no previous record of anthrax in this area. An
      emergency response was undertaken to reduce the scale of environmental
      contamination and dissemination of anthrax spores and hence to reduce the
      likelihood of future outbreaks. One-hundred-and-seventy-two bison, 3 moose (Alces
      alces), and 3 black bear (Ursus americanus) carcasses were found. Visual
      detection of carcasses was enhanced with the use of an airborne, remote infrared
      sensing camera mounted externally on a helicopter. Fifty-five percent of the
      carcasses were located in forested or shrub-covered sites where detection would
      not have been likely without the thermal imaging equipment. Carcasses were
      disposed of by incineration and the sites were decontaminated with formaldehyde.
      Application of formaldehyde to carcasses prevented scavenging. The outbreak
      occurred after a prolonged period of drying between April and mid-July 1993 which
      followed several successive years of flooding of bison habitat. The "spore
      concentration hypothesis" provides the most conservative explanation for the
      occurrence of anthrax under the observed conditions.

PMID- 8548685
TI  - Regulation of bovine acute phase responses by recombinant interleukin-1 beta.
AB  - The acute phase response is a collection of physiologic changes initiated early
      in the inflammatory process. This response is comprised of both localized changes
      at the site of infection or injury and the initiation of systemic responses, such
      as the increase in production of acute phase proteins. Cytokines such as
      interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) play key roles in the
      regulation of acute phase response in the species studied to date. To better
      characterize the acute phase response of cattle, recombinant bovine (rBo). IL-1
      beta was administered to cattle. A single administration of rBoIL-1 beta was able
      to induce a dose dependent increase in body temperature, circulating leukocytes,
      and serum haptoglobin and fibrinogen concentrations, as well as a decrease in
      plasma zinc concentration. Five daily administrations of rBoIL-1 beta resulted in
      heightened and prolonged elevations of haptoglobin and fibrinogen. In addition,
      alpha 1-acid glycoprotein levels were increased, a response not seen after a
      single administration of rBoIL-1 beta. These results indicate that IL-1 is an
      important regulator of the acute phase response in cattle.

PMID- 8548687
TI  - Detection of toxin genes in Escherichia coli isolated from normal dogs and dogs
      with diarrhea.
AB  - The etiology of acute, nonviral diarrhea in dogs is poorly understood.
      Enterotoxigenic and verotoxigenic Escherichia coli are causal agents of diarrhea
      in humans, pigs, and cattle, but the association of these toxigenic E. coli with
      diarrhea in dogs has not been explored to a significant extent. In this study,
      DNA hybridization and PCR amplification were used to identify the frequency with
      which the genes for E. coli enterotoxins (STap, STb, and LTI) and verotoxins (VT1
      and VT2) occur in association with diarrhea in dogs. Genes for VT1 (8.9%), VT2
      (22.2%), STa (26.7%), and STb (4.4%) were identified in E. coli cultured from
      feces of 20 of 45 dogs (44.4%) with diarrhea. Genes for VT2, STa, and STb were
      not identified in feces from normal dogs. Genes for VT1 were observed in similar
      proportions in fecal samples from diarrheic (8.9%) and normal (12.3%) dogs. Heat
      labile enterotoxin (LTI) was not detected in fecal samples from either diarrheic
      or normal dogs. Our results suggest that heat stable enterotoxins and VT2 may be
      causally associated with diarrhea in dogs. Dogs appear to be able to carry VT1
      producing E. coli without showing overt signs of disease.

PMID- 8548688
TI  - A serological survey of bovine syncytial virus in Ontario: associations with
      bovine leukemia and immunodeficiency-like viruses, production records, and
      management practices.
AB  - Of the 920 cows tested, 56.7% showed antiretroviral serological reactivity.
      Prevalence rates (95% confidence interval) of antiretroviral antibodies among
      individual dairy cows in Ontario were: BIV 5.5% (4.0-7.0), BLV 25.7% (22.9-28.6),
      and BSV 39.6% (36.4-42.8). The following percentages of cows showed serological
      reactivity against the specified retroviruses: BIV 2.3%, BLV 14.0%, BSV 27.5%,
      BIV and BSV 1.3%, BIV and BLV 0.9%, BLV and BSV 9.9%, BIV and BLV and BSV 0.9%.
      These rates of sero-positivity are similar to those found in other countries.
      Serological test results were not adjusted for sensitivity and specificity. The
      prevalence rates of antibodies to the three retroviruses (BIV, BLV, and BSV) were
      significantly different, but no associations were observed between specific
      retroviral serological test results among individual cows. The prevalence rates
      of BIV and BSV seropositivity were constant across Ontario, whereas, there was a
      significant trend for the prevalence rate of BLV seropositivity to decrease going
      from southwestern to eastern Ontario; cows in eastern Ontario had approximately
      half the prevalence rate of those in southwestern Ontario. Cows that were
      seropositive for BSV were significantly older than BSV seronegative cows. There
      was no association between culling rate and BSV serology. Significant negative
      associations were found with winter or summer housing of calves separate from
      adults and summer outdoor exercise for dry cows. The use of calf hutches in the
      summer had a significant positive association with BSV seropositivity. Regression
      analyses were done to assess the association of retroviral (BIV, BLV, and BSV)
      seropositivity on calving interval, milk somatic cell count, and milk production.
      Serological test results for BIV, BLV, and BSV were entered into all models and
      all models were adjusted for intra-cluster (intraherd) correlation. Herd size and
      age were found to be important confounding variables. BIV seropositivity was not
      associated with any changes in production using this approach, however when
      considered in isolation BIV seropositivity remained associated with decreased
      milk production. BLV seropositivity was significantly associated with longer
      calving intervals and higher somatic cell counts in older cows. As well, in older
      cows, BSV seropositivity was significantly associated with higher milk
      production.

PMID- 8548689
TI  - Production and characterization of monoclonal antibodies to Actinobacillus
      pleuropneumoniae serotype 5b.
AB  - Monoclonal antibodies specific for capsular polysaccharide (CPS) and
      lipopolysaccharide (LPS) of A. pleuropneumoniae serotype 5b were generated by
      hybridoma cells and selected by indirect ELISA of culture supernatants with
      purified and structurally defined LPS and CPS preparations and their synthetic
      conjugates. It was shown in this study that at least one monoclonal antibody,
      3B4, presented 100% specificity and recognized all A. pleuropneumoniae serotype 5
      field strains tested in a dot-ELISA assay.

PMID- 8548691
TI  - Mitral valve prolapse in 3-year-old healthy Cavalier King Charles Spaniels. An
      echocardiographic study.
AB  - Clinical studies have shown that Cavalier King Charles Spaniels (CKCS) have a
      high prevalence of mitral valvular insufficiency (MVI). Echocardiography has the
      potential to disclose early valvular changes, and the present prospective study
      was designed to investigate the occurrence of mitral valve prolapse (MVP) in
      young CKCS without heart murmurs, and to correlate the degree of MVP with the
      clinical status of the dogs by including CKCS with MVI as well. The study was
      based on blinded evaluations of echocardiographic recordings of mitral valves
      from 34 CKCS and 30 control dogs. Thirteen (87%) of 15 three-year-old CKCS
      without heart murmurs had MVP (2 total and 11 partial), as compared with 1 (7%)
      of 15 three-year-old normal Beagle dogs (P < 0.0001), and none of 15 three-year
      old normal Medium Size Poodles (P < 0.0001). Of 19 CKCS with MVI, MVP was found
      in 84% of the entire group and in 100% of dogs with pulmonary congestion or
      edema. The occurrence of total MVP tended to be higher in the group with MVI
      (47%, 9/19), when compared with the younger CKCS without heart murmurs (13%,
      2/15, P = 0.06). MVP was positively associated with excessive heart rate
      variability (P = 0.003). The radius of curvature of the anterior mitral valve
      leaflet in systole was significantly reduced in dogs with MVP when compared with
      those without (P < 0.0001). In conclusion, this study shows that CKCS at an early
      age have a high occurrence of MVP. This suggests: 1) A genetic predisposition of
      CKCS to MVP; and 2) That MVP is a pathogenetic factor in the development of
      mitral valvular insufficiency. Follow up studies may add further support to these
      proposals, and clarify whether echocardiography may be an aid in selecting CKCS
      for future breeding.

PMID- 8548690
TI  - Study of immune function in inbred miniature pigs vaccinated and challenged with
      suid herpesvirus 1.
AB  - Specific immune responses of inbred miniature pigs following vaccination and
      challenge with suid herpesvirus 1 (SHV-1) were determined. Vaccination of swine
      with SHV-1 elicited both specific neutralizing antibody and lymphoproliferative
      responses. Moreover, pigs vaccinated with SHV-1 were fully protected against a
      lethal virus challenge. Pigs vaccinated with a recombinant (r) SHV-1 virus,
      followed by challenge with a virulent SHV-1, had lower percentages of circulating
      T- and B-lymphocytes, and showed a significant (P < or = 0.05) reduction in
      peripheral blood mononuclear cell (PBMC) antibody-dependent cell-cytotoxicity
      than control (noninfected, SHV-1 sero-negative) animals. From the 5th through the
      8th week of postchallenge, rSHV-1 was isolated from 2 of 4 pigs. Presence of r
      virus was indicative that PBMC were infectious in vivo. The rSHV-1, with beta
      galactosidase activity, was only recovered from ConA- and IL-2-stimulated primary
      PBMC cocultivated with porcine kidney cells. Control pigs exposed to challenge
      SHV-1 elicited both specific neutralizing antibody and lympho-proliferative
      responses followed by subsequent infection. These infected pigs, compared to
      control pigs, had significantly (P < or = 0.05) lowered percentages of T- and B
      lymphocytes, lowered T-cell mitogenic responses, variable PBMC counts, and
      lowered blood phagocytic cell function. When PBMC from control pigs were cultured
      and infected with SHV-1, the virus caused a significant (P < or = 0.05)
      suppression of T-cell proliferation and PBMC mitochondrial dehydrogenase and
      macrophage activities.

PMID- 8548692
TI  - Tissue reaction and immunity in swine immunized with Actinobacillus
      pleuropneumoniae vaccines.
AB  - These studies were done to develop a subunit vaccine for swine that would protect
      against disease, but not create unacceptable tissue reactions at the immunization
      site. Swine were used to evaluate the local effects of subunit vaccines prepared
      from extracts of Actinobacillus pleuropneumoniae serotype 1 containing one of a
      wide variety of adjuvants. The antigen was an anionic fraction of a saline
      extract of A. pleuropneumoniae (ANEX). The adjuvants used were vegetable oils
      (peanut, sesame, canola, or corn oils, vitamin E, or Lipposyn II emulsion);
      mineral oil (Marcol-52) and other materials (aluminum hydroxide, polyethylene
      glycol, Quil-A, Amphigen, or Emulsigen-Plus). Two types of experiments were done.
      In the 1st set of experiments, pigs were given multiple simultaneous injections
      in different sites and euthanized on days 1, 3, 7, 14, 21, or 28. Tissues were
      examined for gross and histopathological lesions. In the 2nd set of experiments,
      48 pigs were allocated to 6 groups and vaccinated twice with a vaccine containing
      ANEX antigen combined with one of various adjuvants. Antibody responses and
      protection from challenge were evaluated. Among the adjuvants that were tested,
      mineral oils induced protective immunity, although the mineral oil Marcol-52
      resulted in severe tissue reactions. The vegetable oils induced little protective
      immunity, and some of them were quite irritating. The response to the other
      materials ranged from little irritation or protection induced by the vaccine
      containing aluminum hydroxide to effective protection without irritation after
      vaccination with ANEX/Amphigen or ANEX/Emulsigen-Plus combinations. In
      conclusion, swine were protected against disease by a subunit vaccine that did
      not create unacceptable tissue reaction at the immunization site.

PMID- 8548693
TI  - Development of a specific biotinylated DNA probe for the detection of
      Renibacterium salmoninarum.
AB  - A specific DNA probe for the identification of Renibacterium salmoninarum, the
      causative agent of bacterial kidney disease (BKD), was developed from one of 3
      clones pRS47, pRS49, and pRS26 of 5.1 kb, 5.3 kb, and 11.3 kb, respectively. The
      biotinylated pRS47/BamHI insert probe was tested on 3 dilutions of DNA extracted
      from 3 strains of R. salmoninarum and from 1 strain each of Arthrobacter
      protophormiae, Aeromonas salmonicida, Corynebacterium aquaticum, Carnobacterium
      piscicola, Listonella anguillarum, Micrococcus luteus, Pseudomonas fluorescens,
      Vibrio ordalii, and Yersinia ruckeri. In a dot blot assay, this probe hybridized
      only with the DNA from the R. salmoninarum strains. When used on kidney samples
      from fish challenged with R. salmoninarum, the dot blot hybridization assay with
      the probe was found to be as sensitive as culture. In a fluorescent antibody
      test, samples that were negative in culture and dot blot hybridization showed no
      more than one fluorescing cell in 50 microscopic fields examined. This DNA probe,
      therefore, has the potential for use in the diagnosis of BKD of fish.

PMID- 8548694
TI  - The influence of supplemental chromium and vaccines on the acute phase response
      of newly arrived feeder calves.
AB  - The acute phase response as indicated by serum haptoglobin and total haemolytic
      complement activity (CH50) was measured in 72 cross-bred steer calves purchased
      at sales in Ontario. During the 28 day (d) trial, 18 steers were randomly
      assigned to each of the following groups: 1) control; 2) vaccinated (Infectious
      Bovine Rhinotracheitis, Parainfluenza-3, Bovine Viral Diarrhea, Bovine
      Respiratory Synctial Virus vaccine plus Pasteurella haemolytica vaccine); 3)
      supplemental chelated Cr (0.14 mg/kg); and 4) Cr plus vaccines. Haptoglobin
      concentrations were low at arrival, increased (P < 0.05) on day 7, and returned
      to near initial levels (P > 0.05) by day 14. Supplemental Cr reduced (P < 0.05)
      haptoglobin on day 7 when morbidity was highest. Following antibiotic treatment
      for respiratory disease haptoglobin was lower (P < 0.05) than during morbidity;
      however, during morbidity, haptoglobin concentrations were not greater in sick
      calves (P > 0.05) than in healthy calves. Complement activity was lowest on day 7
      (P < 0.05) and peaked on day 14 (P < 0.05). Complement activity tended to be
      lower on day 7 for vaccine, Cr, and Cr+ vaccine groups; however, the difference
      from controls was not significant (P > 0.10). Complement activity did not
      increase on day 14 (P > 0.05) with Cr supplementation as in other treatments.
      Morbid calves had lower (P < 0.05) CH50 activity than healthy calves on day 14.
      Following antibiotic treatment, the Cr-supplemented group had higher (P < 0.05)
      CH50 than during morbidity. In general, chromium supplementation reduced the
      acute phase response in newly arrived feeder calves.

PMID- 8548695
TI  - Radiographic and immunohistochemical analysis of leukocyte adhesion deficiency in
      Holstein heifers.
AB  - Radiographic and immunohistochemical analyses were performed in two Holstein
      heifers with leukocyte adhesion deficiency (BLAD). Severe bone resorption,
      osteolysis and severe progressive periodontitis in submandibula due to
      dysfunction of leukocytes in heifers affected with BLAD were demonstrated by
      radiographic examination. Immunohistochemical analysis of lymph nodes using anti
      CD18 monoclonal antibody demonstrated that CD18-positive cells were not found on
      those from a heifer affected with BLAD, whereas CD18-positive cells were clearly
      present in lymph nodes from a clinically normal heifer. These characteristic
      findings support the importance of adherence-dependent leukocyte functions in
      host defense.

PMID- 8548696
TI  - Treating AIDS: hope and despair.

PMID- 8548697
TI  - Treating AIDS: hope and despair.

PMID- 8548698
TI  - Treating AIDS: hope and despair.

PMID- 8548699
TI  - Pitfalls of health care programs in Tanzania.

PMID- 8548700
TI  - The war on tobacco use.

PMID- 8548701
TI  - US physician warns Canadians about privatization.

PMID- 8548702
TI  - Truth first casualty at Dieppe.

PMID- 8548703
TI  - Genetic counselling and testing for susceptibility to breast, ovarian and colon
      cancer: where are we today?
AB  - Recent advances in our understanding of the genetic characteristics of cancer
      will change approaches to genetic screening and counselling. Cancer results from
      multiple, cumulative mutations in genes that regulate cell replication and
      differentiation. In familial cancer a germ-line mutation is passed on in an
      autosomal dominant pattern, but cancer will develop in people who inherit the
      defect only if other mutations also occur in susceptible somatic cells. The
      tumour-suppressor gene known as BRCA1 is thought to affect half of those families
      who have an inherited breast cancer syndrome and most families with a breast and
      ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the
      remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis
      colon cancer (HNPCC) is caused by mutations in surveillance genes that protect
      DNA from the spontaneous errors that occur during cell division. Because there
      are no outcome data on which to base practice guidelines for genetic screening or
      management of asymptomatic carriers in families at risk, testing should be
      restricted to research settings.

PMID- 8548704
TI  - Mobilizing physicians to conduct clinical intervention in tobacco use through a
      medical-association program: 5 years' experience in British Columbia.
AB  - During the last 5 years, a program run by the medical association in British
      Columbia has recruited 23% of the province's general practitioners (GPs) to take
      an active, systematic approach to clinical intervention in tobacco use. Another
      9% of GPs (considered "semi-active") regularly use the program's educational
      materials for patients, and another 25% have been trained in intervention or have
      been given intervention materials or both. If the cessation rate (rate of
      patients who quit smoking who would not otherwise have done so) was 4% among
      physicians actively involved in intervention and 2% among physicians considered
      semi-active, in 1995 an estimated 4700 smokers quit and were followed by their
      GPs as a result of the program. Another 135,000 smokers received brief
      counselling from their GPs and were also followed. This article reviews the
      strategies and methods used in this program to mobilize physicians.

PMID- 8548705
TI  - Abortion induced with methotrexate and misoprostol.
AB  - OBJECTIVE: To determine the outcome and side effects of a new drug protocol to
      induce abortion. DESIGN: Case series. SETTING: An urban primary care practice.
      PATIENTS: One hundred consecutive patients who requested elective termination of
      pregnancies of less than 8 weeks' gestation. INTERVENTION: Subjects received
      methotrexate (50 mg/m2 body surface area, administered intramuscularly) and, 3
      days afterward, misoprostol (800 micrograms, given vaginally). OUTCOME MEASURES:
      Number of abortions induced within 24 hours and within 10 days of misoprostol
      administration, number of surgical aspirations conducted because of incomplete
      abortion, mean amount of bleeding and pain and the number of women who, if faced
      with the same situation, said they would again choose a drug-induced abortion
      over a surgical one. RESULTS: Abortion occurred within 24 hours of misoprostol
      administration among 48 women and within 10 days among 69 women. In total, 89
      women had an abortion without surgical aspiration. Of these women, 71 said they
      would choose a drug-induced abortion if faced with the choice again. CONCLUSION:
      Abortion induced with methotrexate and misoprostol appears to be a feasible
      alternative to surgical abortion and deserves further study.

PMID- 8548706
TI  - Factors influencing the emigration of physicians from Canada to the United
      States.
AB  - OBJECTIVE: To determine whether location of postgraduate medical training and
      other factors are associated with the emigration of physicians from Canada to the
      United States. DESIGN: Case-control study, physicians were surveyed with the use
      of a questionnaire mailed in May 1994 (with a reminder sent in September 1994),
      responses to which were accepted until Dec. 31, 1994. PARTICIPANTS: Physicians
      randomly selected from the CMA database, 4000 with addresses in Canada and 4000
      with current addresses in the United States and previous addresses in Canada.
      OUTCOME MEASURES: Sex, age, location of undergraduate and postgraduate medical
      training, qualifications, practice location, opinions concerning residence
      decisions, current satisfaction and plans. RESULTS: The overall response rate was
      49.6% (50.0% among physicians in the United States and 49.2% among those in
      Canada). Age and sex distributions were similar among the 8000 questionnaire
      recipients and the nearly 4000 respondents. Physicians living in the United
      States were more likely to be older (mean 53.2 v. 49.6 years of age), male (87%
      v. 75%) and specialists (79% v. 52%) than those practising in Canada.
      Postgraduate training in the United States was associated with subsequent
      emigration (odds ratio 9.2, 95% confidence interval 7.8 to 10.7). However, in
      rating the importance of nine factors in the decision to emigrate or remain in
      Canada, there was no significant difference between the two groups in the rating
      assigned to location of postgraduate training. Professional factors rated most
      important by most physicians in both groups were professional/clinical autonomy,
      availability of medical facilities and job availability. Remuneration was
      considered an equally important factor by those in Canada and in the United
      States. Six of seven personal/family factors were rated as more important to
      their choice of practice location by respondents in Canada than by those in the
      United States. Current satisfaction was significantly higher among respondents in
      the United States. Most physicians in each group planned to continue practising
      at their current location. Of Canadian respondents, 22% indicated that they were
      more likely to move to the United States than they were a year beforehand,
      whereas 4% of US respondents indicated that they were more likely to return to
      Canada. CONCLUSIONS: Factors affecting the decision to move to the United States
      or remain in Canada can be categorized as "push" factors (e.g., government
      involvement) and "pull" factors (e.g., better geographic climate in the US).
      Factors can also be categorized by whether they are amenable to change (e.g.,
      availability of medical facilities) or cannot be managed (e.g., proximity of
      relatives). An understanding of the reasons why physicians immigrate to the
      United States or remain in Canada is essential to planning physician resources
      nationally.

PMID- 8548707
TI  - Medical abortion: what does the research tell us?
AB  - Dr. Ellen R. Wiebe's study of the use of methotrexate and misoprostol in
      combination for early termination of intrauterine pregnancy (see pages 165 to 170
      of this issue) is the first Canadian study of the use of this drug combination
      for medical abortion. The authors compare Wiebe's findings with those of earlier
      studies on methotrexate and misoprostol, as well as with European findings on the
      use of mifepristone with prostaglandins. The authors argue that although the
      methotrexate-misoprostol combination appears to be reasonably safe for the woman,
      the failure rate and the teratogenicity of methotrexate and misoprosol give cause
      for concern. The authors conclude that medical abortions ought to be offered only
      where there is adequate access to laboratory and surgical facilities and where
      losses to follow-up are systematically minimized to reduce the potential for
      continued pregnancy resulting in congenital abnormality.

PMID- 8548708
TI  - Yes, minister, Canadians need strong tobacco-control legislation now!
AB  - At a meeting with federal health minister Diane Marleau on Nov. 16, 1995, the CMA
      and other health organizations were told that the minister plans to propose
      comprehensive measures to limit the manufacture, sale and marketing of tobacco
      products. On Dec. 11, 1995, the minister announced a "Blueprint on Tobacco
      Control," which outlined the scope of her plan to introduce tobacco legislation
      in the spring. On the basis of adamant support for tobacco control from all
      levels of the organization, the CMA urges the minister to move quickly. It also
      advocates regulating tobacco as a hazardous product in the meantime. Physicians
      can take a wide variety of actions to intervene with patients and add their voice
      to antitobacco lobbying efforts in 1996.

PMID- 8548709
TI  - Inhibiting calpain, rescuing cells.
AB  - Drs. John Elce and Peter Davies, biochemists at Queen's University, Kingston,
      Ont., are investigating the molecular structure of calpain, an enzyme that has
      been implicated in the cellular damage that occurs after such events as
      myocardial infarction and stroke. This damage is precipitated by an imbalance in
      the regulation of calpain that arises as an indirect result of ischemia. Elce and
      Davies hope that their research, which involves techniques such as recombinant
      DNA technology and x-ray crystallography, will lead to the development of a
      calpain inhibitor that will prevent such damage from occurring and enhance
      recovery.

PMID- 8548710
TI  - A surgeon with AIDS made the most of borrowed time.
AB  - Dr. Orville Messenger and his wife, Dorothy wrote a book, Borrowed Time, which
      chronicled his decade-long struggle with AIDS. The disease developed following a
      1985 blood transfusion. A general and thoracic surgeon who also worked for the
      Canadian Medical Protective Association, Dr. Messenger wrote the book to raise
      public awareness, and money for AIDS research, prevention and treatment. He died
      Dec. 13, 1995--exactly 10 years after being told to take a blood test because of
      possible HIV infection.

PMID- 8548711
TI  - Tough tobacco-control legislation begins to have an impact in Ontario.
AB  - In 1994 the Ontario government passed one of the world's toughest packages of
      antitobacco legislation. The Tobacco Control Act places restrictions on who can
      sell tobacco products, provides for severe penalties for retailers who sell to
      minors, bans smoking in many public places and severely restricts the use of
      designated smoking areas in others. The province has had antismoking legislation
      before, but enforcement was lax; this time enforcement of the law, particularly
      as it concerns retailers who sell to minors, has been given priority Brenda
      Gibson asks if these tough new measures are working.

PMID- 8548712
TI  - Global spread of TB worrying trend for Canadian physicians.
AB  - Canada has one of the world's lowest rates of tuberculosis infection, but that
      doesn't mean the disease poses no threat here. TB represents a growing problem in
      prisons and among Canadians of native and Asian descent. Patients with active TB
      can be misdiagnosed because few physicians ever see the disease and because the
      bacillus can infect organs other than the lungs. Frequent screening of at-risk
      populations and a rigorous course of antibiotics for those who are infected are
      recommended.

PMID- 8548713
TI  - Ethical boundaries in genetic testing.
AB  - The scarcity of resources that can be allocated to genetic testing will
      ultimately limit the number of diseases subjected to molecular analysis. Medical
      student David Allan, who claimed first prize in CMAJ's 1995 Logie Medical Ethics
      Essay Contest, looks at the ethical principles that should guide decisions about
      genetic testing, and the importance of communicating these principles to patients
      and their families.

PMID- 8548714
TI  - Madeleine's death.
AB  - Despite visits to two physicians and two hospitals within 4 days in September
      1994, 7-week-old Madeleine Hunter died of flu-related dehydration. The coroner at
      an inquest into the baby's death said he had never seen a case in which so many
      things went wrong. The coroner's jury, which made 46 recommendations, determined
      that physicians and others involved in the care of very small infants should give
      "due respect to the instinct of the mother." Madeleine's mother, Georgina Hunter,
      recounts the story of her baby's death.

PMID- 8548715
TI  - Support groups in psychiatry: an untapped resource.

PMID- 8548716
TI  - Direct cost of depression: analysis of treatment costs of paroxetine versus
      Imipramine in Canada.
AB  - OBJECTIVE: To assess the potential economic impact of new and more expensive
      antidepressants on the overall cost of treatment using cost-effectiveness
      analysis. METHOD: For this analysis, a computerized decision tree of clinical
      practice was developed to model the 12-month treatment of moderate to severe
      depression in Canada. To complete the model, data were obtained from physician
      panels, the Ontario Ministry of Health, and clinical comparative trials of
      paroxetine, a selective serotonin reuptake inhibitor, and imipramine, a tricyclic
      antidepressant. RESULTS: The overall cost of treatment when paroxetine 30 mg per
      day was used first-line was found to be lower than when generic imipramine was
      used as the initial therapy ($1697 versus $1793). The higher drug cost of
      paroxetine ($1.69 per day) versus imipramine ($0.05 per day) was offset by a
      higher rate of treatment failures with the tricyclic necessitating an alternate
      therapy, additional physician visits and/or hospitalization. Sensitivity analysis
      of key variables determined that drug price and relapse rates after
      discontinuation were relatively insensitive predictors of the overall cost of
      care. More important was the continuation rate while on different therapies.
      CONCLUSION: Paroxetine demonstrated a cost-benefit relative to imipramine when
      the continuation rate was > or = 47%. Clinical trials of paroxetine have reported
      continuation rates of 41% to 65%, suggesting that paroxetine is a cost-effective
      alternative to imipramine in the 1-year management of patients with moderate to
      severe depression.

PMID- 8548717
TI  - A single mothers' group for mothers of children attending an outpatient
      psychiatric clinic: preliminary results.
AB  - OBJECTIVES: To provide a preliminary report of data from 2 support groups for
      single mothers, all of whom were mothers of children attending a child outpatient
      psychiatric clinic. The groups' 2 purposes were: 1. to assess the feasibility of
      adding structured evaluation to a common clinical intervention; 2. to improve
      single mothers' parenting skills through raised levels of self-esteem, increased
      capacity for family functioning and reduced levels of depression. METHOD: Three
      structured evaluation instruments were used to measure the domains of self
      esteem, family functioning and depression. These instruments were given to both
      groups of women on 3 occasions: 1. before the group; 2. after the group; 3. at a
      follow-up session 4 months after group termination. Open-ended questions were
      also asked at group termination. RESULTS: The questionnaire response rate was
      100%; overall response rate for the 3 open-ended questions was 89%. Comparisons
      of pre-group and post-group scores showed that there was a significant increase
      in self-esteem (p < 0.01) and significant improvements in family functioning (p <
      0.05) and depression (p < 0.01). CONCLUSION: It is possible to introduce a
      structured evaluation component into a common clinical intervention, and this
      support group seemed to assist single mothers' parenting skills. Methodologic
      concerns and future directions are discussed.

PMID- 8548718
TI  - Shared psychotic disorder: a critical review of the literature.
AB  - OBJECTIVE: To search the literature to reassess the concept of shared psychotic
      disorder (SPD) using modern nosology and current biopsychosocial formulation.
      METHOD: Analyzing published case reports from 1942 through to 1993 that meet DSM
      IV criteria for SPD according to patient age, sex, nature and duration of the
      relationship with the "primary", length of exposure to primary's psychosis,
      family psychiatric history, comorbidity, social isolation of the dyad, presence
      of hallucinations, delusional type, and the diagnosis of the primary. RESULTS:
      Findings revealed: 1. males and females were affected with equal frequency; 2.
      there was equal prevalence in younger and older patients; 3. the majority of
      shared psychoses (90.2%) were equally distributed among married couples,
      siblings, and parent-child dyads; 4. comorbid dementia, depression, and mental
      retardation were common; 5. hallucinations were common; 6. the majority of dyads
      (67.3%) were socially isolated. CONCLUSIONS: SPD probably occurs in premorbidly
      disposed individuals in the context of social isolation which is shared with a
      psychotic person.

PMID- 8548719
TI  - A case-control study of corticosteroid exposure as a risk factor for clinically
      diagnosed depressive disorders in a hospitalized population.
AB  - OBJECTIVE: Depressive symptoms may be a side effect of exogenous corticosteroids.
      However, the literature does not confirm that corticosteroid exposure is
      associated with the occurrence of depressive disorders. The objective of this
      study was to determine whether or not corticosteroid exposures are associated
      with clinical diagnoses of depressive disorders in hospitalized patients. METHOD:
      The study used a case-control design. Cases and 2 control groups were selected
      from a health records case summary database maintained at the Calgary General
      Hospital. Additional data were collected by chart review. RESULTS: The analysis
      reproduced associations between depressive diagnoses and several psychosocial and
      biological risk factors. However, the data did not suggest that corticosteroids
      were associated with an elevated risk of depressive diagnoses. In fact, odds
      ratios for corticosteroid exposure were less than 1, consistent with a protective
      effect. CONCLUSIONS: Although corticosteroids may produce depressive symptoms as
      a side effect, corticosteroid exposures are not associated with an elevated risk
      of clinically diagnosed depressive disorders in hospitalized patients. There are
      several possible explanations for this. Depressive syndromes associated with
      corticosteroid exposure may not clinically resemble depressive disorders, and may
      not warrant a diagnosis of a depressive disorder. Alternatively, clinicians may
      not identify and formally diagnose depressive disorders caused by
      corticosteroids.

PMID- 8548720
TI  - [Experimental and clinical pharmacology of psychostimulants].
AB  - OBJECTIVE: To examine the fact that, after 50 years, the introduction of
      amphetamines for therapeutic purposes, psychostimulants such as methylphenidate
      have proved to be effective medications used in the treatment of childhood
      hyperactivity, yet misunderstood. METHOD: A review of the literature is
      undertaken on the use of psychostimulants in children and adults. RESULTS:
      Studies evaluating their helpfulness in adults are for the most part outdated and
      nonexploratory. CONCLUSION: their rehabilitation could prove to be useful for
      young and older adults, on condition that their target syndromes are studied more
      thoroughly.

PMID- 8548721
TI  - Interpersonal disorder in schizoid and avoidant personality disorders: an
      attachment perspective.
AB  - OBJECTIVE: To investigate the characteristics related to avoidant attachment of
      13 schizoid/avoidant psychiatric outpatients and 20 nonschizoid/avoidant
      psychiatric outpatients. METHOD: Three scales ("maintains distance in
      relationships", "high priority on self-sufficiency" and "attachment relationship
      is a threat to security") differentiated schizoid and avoidant personality
      disordered patients from other personality disordered patients. RESULTS: The
      results are discussed in terms of the attachment and DSM diagnostic models of
      avoidant styles in relationships. CONCLUSION: The 2 groups of schizoid and
      avoidant personality disordered patients were not significantly different on the
      desire for close affectional bonds scale.

PMID- 8548722
TI  - Brief psychiatric hospitalization: preliminary experience with an urban short
      stay unit.
AB  - OBJECTIVE: To present data from the recently implemented psychiatric short-stay
      units (SSUs) in metro Halifax. There are few data describing SSUs and factors
      associated with successful outcome. METHODS: A 4-month retrospective chart review
      of 124 patients. RESULTS: Patients tended to be single, unemployed young adults,
      with a past history of psychiatric admission. Most patients were admitted
      voluntarily. There was an equal sex ratio. Mean length of stay for all patients
      was 2.5 days. Adjustment disorder was the diagnosis most responsible for
      admission. CONCLUSION: Many psychiatric inpatients may benefit from brief
      hospitalization. Brief hospitalization results in reduced health care costs.

PMID- 8548723
TI  - Folie simultanee in monozygotic twins.
AB  - OBJECTIVE: To present a case report of folie simultanee in monozygotic twins. The
      literature describing folie a deux in twins is also reviewed and the common
      clinical findings are presented. METHOD: Case presentation and review of the
      literature. RESULTS: Clinical observations of monozygotic twins with folie
      simultanee suggest that the delusions tend to progress over time with each twin
      reinforcing the delusion in the second. CONCLUSIONS: The concept of a delusion
      resonating between individuals may account for the rapid progression and
      escalation of these delusions.

PMID- 8548724
TI  - Re: The use of placebos in clinical trials for acute schizophrenia.

PMID- 8548725
TI  - Placebo reconsidered.

PMID- 8548726
TI  - Re: Reviewers of manuscripts submitted to The Canadian Journal of Psychiatry.

PMID- 8548727
TI  - Serotonin syndrome from fluvoxamine and buspirone.

PMID- 8548728
TI  - Occult central hypothyroidism in depression: a case study.

PMID- 8548729
TI  - Fluvoxamine and mandibular dystonia.

PMID- 8548730
TI  - Involuntary sperm emission with fluoxetine.

PMID- 8548731
TI  - Loss of chromosomes 22 and 14 in the malignant progression of meningiomas. A
      comparative study of fluorescence in situ hybridization (FISH) and standard
      cytogenetic analysis.
AB  - The majority of meningiomas are classified as typical and have a relatively
      benign course. However, approximately 10% are diagnosed as atypical, anaplastic,
      or malignant and have a worse prognosis. The genetic differences between the
      typical and higher grade meningiomas are not well characterized, although there
      appear to be increasingly complex karyotypic changes associated with the higher
      grade tumors. Because higher grade meningiomas are not common tumors, and because
      of the inherent problems associated with the culturing of tumors, the use of
      interphase cytogenetic techniques with paraffin-embedded archival material is
      desirable for studying these neoplasms. To determine its accuracy in detecting
      aneuploidy, we performed fluorescence in situ hybridization (FISH) on 2-micron
      paraffin sections of nine previously karyotyped meningiomas using an alpha
      satellite probe for chromosomes 14 and 22. Sections of normal tissue from six
      patients without malignancy were used as controls. FISH analysis detected all of
      the chromosome losses in the meningioma cases that had been characterized
      cytogenetically. In five cases, cell lines not detected by standard cytogenetics
      were identified by FISH. These results indicate that FISH is a reliable method
      for detecting chromosomal loss and may be more sensitive than standard
      cytogenetics alone. Furthermore, the results of this study support the concept
      that loss of chromosome 14 is associated with malignant progression in
      meningiomas.

PMID- 8548732
TI  - Malignant progression of an HPV16-immortalized human keratinocyte cell line
      (HPKIA) in vitro.
AB  - The DNA of human papillomavirus (HPV) types found in cervical carcinomas can
      immortalize primary human keratinocytes. However, in analogy to tumor progression
      in vivo, HPV-immortalized keratinocytes require secondary events for malignant
      conversion. Here, we report on an HPV16-immortalized keratinocyte cell line
      (HPKIA) which after gamma-irradiation and long term culturing in vitro has
      acquired the ability to form squamous cell carcinomas in nude mice. The HPV16
      integration locus and the viral transcript pattern of HPKIA cells at different
      passages have remained unaltered. A difference in cytokeratin expression was
      noted for HPKIA-induced cysts and HPKIA-induced carcinomas. In addition to the
      expression of suprabasal markers such as cytokeratin 10 and involucrin,
      carcinomas also express cytokeratin 8 and 18. The latter cytokeratin pair is
      often expressed in high-grade cervical neoplasia and cervical squamous cell
      carcinomas. Extensive cytogenetic analyses of nontumorigenic HPKIA cells and
      their tumorigenic segregants has revealed no single chromosomal abnormality which
      is confined to all tumorigenic cells. A consistent net loss of chromosomes 3, 5,
      9, 12, and 22 was evident for all malignant cells. HPKIA cells represent all
      stages of transformation and are thus useful for defining secondary genetic
      events that potentially mark malignant progression in human cells in vivo.

PMID- 8548733
TI  - Cytogenetical findings of recurrent meningiomas. A study of 10 tumors.
AB  - Cytogenetic analyses of 10 cases of recurrent meningiomas growing in culture
      between 1-10 days are reported, of which seven showed benign morphology, one
      atypical, and two, malignant features. Normal karyotypes with nonclonal
      alterations were found in three cases, one case with only monosomy 22, and
      complex karyotypes in the remaining six. Four cases were hypodiploid, one
      pseudodiploid, and one hyperdiploid. The chromosomes most often involved in
      structural rearrangements were 1, 7, and 14 and the losses were chromosomes 7,
      10, 14, 15, 18, and 22. Ring chromosome, dicentrics, double minutes, and
      association between satellites were found in one case. These complex karyotypes
      with hypodiploidy, structural rearrangements, and other markers in recurrent
      meningiomas may indicate aggressive tumor characteristics.

PMID- 8548734
TI  - The BCL-1, BCL-2, and BCL-3 oncogenes are involved in chronic lymphocytic
      leukemia. Detection by fluorescence in situ hybridization.
AB  - The putative oncogenes BCL-1, BCL-2, and BCL-3 are commonly rearranged by
      translocations to the immunoglobulin genes in B-cell malignancies. However,
      Southern blotting rarely detected their involvement in chronic lymphocytic
      leukemia (CLL). This discrepancy could stem from some unique features of the
      oncogenesis of CLL or be due to shortcomings of Southern blotting. We have
      therefore evaluated the role of fluorescence in situ hybridization (FISH) in the
      detection of these oncogenes in CLL. Twenty consecutive CLL patients were studied
      by FISH for the detection of BCL-1, BCL-2, or BCL-3 rearrangement and for the
      presence of trisomy 12. Selected patients were also evaluated by classical
      cytogenetic techniques and by Southern blot analysis. Juxtaposition of JH and BCL
      1 was demonstrated in 10 (50%), BCL-2 in three (15%), and BCL-3 in four (20%) of
      the patients. Trisomy 12 was detected by FISH in 11 (55%) patients. The
      coexistence of trisomy 12 and translocation of the BCL-1 oncogene was common.
      Three of the patients had chromosomal aberrations compatible with those detected
      by FISH. In contrast, in none of the five patients selected by their positive
      FISH findings was a rearrangement demonstrated by Southern blotting. We conclude
      that FISH is a sensitive method for the detection of oncogene involvement in CLL.
      Mainly BCL-1, but also BCL-2 and BCL-3, are commonly translocated to the
      immunoglobulin heavy chain locus on chromosome 14. These translocations are often
      associated with trisomy 12. These findings indicate that the BCL oncogenes are
      commonly involved in CLL and lend support to the multi-hit theory of cancer
      development.

PMID- 8548735
TI  - Retrospective investigation of hematopoietic chimerism after BMT by PCR
      amplification of hypervariable DNA regions.
AB  - We report on nine patients submitted to BMT with sex-matched donors and
      investigated by means of PCR amplification of the VNTRs ApoB, D1S80, DXS52, and
      D17S5. In all cases it was possible to detect a polymorphism able to distinguish
      between donor and patient cells, thus allowing us to recognize the presence of
      complete or mixed chimerism. In eight patients PCR analysis showed a complete
      chimerism during the entire follow-up. Only one of these patients relapsed, while
      the others are alive and without any sign of relapse 56.2 months (mean) after
      BMT. Mixed chimerism was detected in only one patient, who relapsed 3 months
      after this finding. These results confirm the usefulness of the study of PCR
      amplified VNTRs in the assessment of marrow engraftment after BMT, mostly in sex
      matched transplants where, in the absence of specific chromosome rearrangements,
      cytogenetic or FISH analysis cannot be used.

PMID- 8548736
TI  - Ectopic nucleolar organizer regions. A common anomaly revealed by Ag-NOR staining
      of metaphases from nine cancers.
AB  - In view of the sparsity of reports on nucleolar organizer regions (NORs) in human
      tumor metaphase chromosomes, we have applied the silver (Ag-NOR) technique to a
      previously studied testicular germ-cell tumor that had an abnormal translocation,
      which involved a 13p, and to nine new sequentially studied tumors. Six of the new
      tumors, and the germ cell tumor, showed ectopic NORs (e.g., at the end of the
      long arm of acrocentrics or metacentrics, or interstitially in metacentrics):
      five carcinomas and a leiomyosarcoma, all of which also revealed numerous
      structural chromosome changes after G-banding. The three tumors that did not show
      ectopic NORs were lymphomas with relatively simple karyotypic changes. It seems
      that the presence of ectopic NORs in the majority of the tumors is a reflection
      of the multiplicity of structural changes in these tumors and does not signify
      that there is any particular propensity for acrocentrics to take part in these
      changes. It was interesting that several of the chromosomes showed large notably
      a metacentric in a squamous cell carcinoma of the skin in which the Ag-NOR
      positive region was seen as an unstained gap in unbanded and G-banded
      chromosomes.

PMID- 8548737
TI  - Cytogenetic evidence that carcinoma in situ is the precursor lesion for invasive
      testicular germ cell tumors.
AB  - A cytogenetic study of two cases of carcinoma in situ of the testis (CIS) and
      their adjacent invasive tumors, one a nonseminomatous germ cell tumor (NS) and
      one a seminoma (SE), revealed similarities in chromosomal pattern between the CIS
      and the invasive lesion in the same patient. These findings present for the first
      time cytogenetic evidence that CIS of the testis and its adjacent germ cell tumor
      are clonally related, which suggests that the CIS is indeed the precursor lesion
      of the invasive tumor.

PMID- 8548738
TI  - Multiple clonal chromosome aberrations in a case of childhood focal nodular
      hyperplasia of the liver.
AB  - A case of focal nodular hyperplasia is described that was accompanied by intense
      reactive stromal changes giving rise to a pseudosarcomatous appearance.
      Cytogenetic study revealed complex karyotypic abnormalities including five
      partially identifiable clonal aberrations and one marker chromosome. The
      composite karyotype was interpreted as: 45-46,XY,add(4)(q21-25)[24],
      add(11)(p14)[24], add (19)(p13)[15], der(20)t(1;20)(q25;p12)[31], add(21)
      (q22)[13],-22[3], +mar[2][cp31]. In addition, quadriradial or complex figures,
      telomeric associations tas, unidentified ring chromosomes, chromosome breaks, and
      markers were seen in some cells. Such cytogenetic findings, although suggestive
      of malignancy, could most likely be related to a nonneoplastic condition, i.e.,
      the unusual florid reactive changes associated with this focal nodular
      hyperplasia.

PMID- 8548739
TI  - Homologous centromere association of chromosomes 9 and 17 in prostate cancer.
AB  - Chromosomal loss in cancer cells has been observed by nonisotopic in situ
      hybridization using pericentromeric probes. Accurate determination of this loss
      depends upon efficient hybridization and visualization of all probe signals in a
      two-dimensional field. Close association of homologous centromeres, reported in
      various normal and tumor tissues, can complicate evaluation and interpretation,
      resulting in the overestimation of actual chromosome loss. Using pericentromeric
      FISH probes for chromosomes 9 (classical and beta-satellite) and 17 (alpha
      satellite), as well as 17q-specific phage probes, we tested the frequency of
      homologous centromere association in normal and malignant prostate tissues and
      lymphoblastoid cells. We found that the pericentromeric region of both chromosome
      9 and 17 associated in prostate tissues, but only chromosome 9 demonstrated
      association in the lymphoblastoid cells. The association observed for chromosome
      9 in both cell types appeared to be limited to the classical satellite III-type
      of heterochromatic, pericentromeric DNA. Using a single-copy probe along with the
      chromosome 17-specific pericentromeric probe, we determined that the association
      did not extend to the chromosome arms, but was limited to the pericentromeric
      region of chromosome 17. To accurately determine chromosome loss, we advocate the
      use of single-copy probes in addition to, or in place of, pericentromeric probes.

PMID- 8548740
TI  - Chromosomal abnormalities in non-neoplastic renal tissue.
AB  - Chromosome aberrations were studied in short-term cultures of non-neoplastic
      renal tissue and tumor tissue in 60 patients, 41 male and 19 female, with renal
      cell cancer (RCC), and in normal renal parenchyma from two cases, one male and
      one female, at autopsy with non-kidney related disease. Cytogenetic analysis of
      the non-neoplastic renal tissue from the patents with RCC revealed clonal
      chromosome aberrations in 32 of 60 (53%) cases: -Y, +Y, +X, +5, +7, +10, +12,
      +13, +18, +21, and del(9)(q12). In all other cases, non-clonal numerical and
      structural chromosome aberrations were observed, except for three cases of
      culture failure. Forty-two cases of RCC yielded clonal chromosomal abnormalities.
      Trisomy 7 was present in 23 cases, loss of Y in 14, trisomy 5 and 12 in three,
      trisomy 18 in two cases, and trisomy 10 in one case. Clonal chromosomal anomalies
      found in two cases from kidneys without neoplasia were trisomy 7, trisomy 12, and
      trisomy 18 in one case, and monosomy of chromosome 15 in the other. The
      proportion of aberrant cells in both cases (with clonal and non-clonal
      aberrations) was, on average, 24%. Apparently, chromosomal abnormalities only
      play a role in the process of oncogenesis when they are in the appropriate stage
      and lineage of differentiation.

PMID- 8548741
TI  - Chromosomal alterations in a case of ganglioglioma.

PMID- 8548742
TI  - Translocation basis for polychromosomal rings.

PMID- 8548743
TI  - SIL/TAL1 recombination in adult T-acute lymphoblastic leukemia and T
      lymphoblastic lymphoma.

PMID- 8548744
TI  - A cytogenetic study of malignant fibrous histiocytoma.
AB  - We report the results of cytogenetic analysis of malignant fibrous histiocytoma
      of soft tissue (MFH). Seven of 12 successfully cultured MFHs had complex clonal
      aberrations, including translocations, deletions, and unidentifiable marker
      chromosomes. Telomeric associations were observed in five and the double minute
      phenomenon in four of seven MFHs with abnormal karyotypes. In one case (a
      storiform-pleomorphic MFH, grade IV) with a complex polyploid karyotype, two
      clonal ring chromosomes were present, one interpreted as r(19)(p13q13), one
      unidentified. In two tumors, clonal structural rearrangements of chromosome 1
      were seen: del(1)(q21) in a storiform-pleomorphic MFH, grade IV, and add (1)(q21
      or q32), t(1;10)(p22;q22) in a myxoid MFH, grade I. The remaining five MFHs had
      normal karyotypes, but in two of them nonclonal, structural aberrations were
      found. The modal chromosome number in the studied MFHs varied widely, but the
      majority of tumors with abnormal karyotypes had polyploid chromosome complements
      (five of seven cases). Our results confirm many of the previous findings and
      indicate that double minutes (dmins) may be more frequent in MFH than previously
      reported.

PMID- 8548745
TI  - Genetic heterogeneity of chromosome 11 associated with tumorigenicity in HeLa D98
      OR cells.
AB  - D98-OR is a tumorigenic subline of HeLa cells. We isolated nine subclones from
      D98-OR and examined their tumorigenicity in nude mice. Three, two, and four
      subclones were highly, weakly, and nontumorigenic, respectively. While they all
      contained two copies of intact chromosome 11, restriction fragment length
      polymorphism (RFLP) analysis revealed that the allelic composition of this
      chromosome differed among them. The highly tumorigenic subclones were
      heterozygous for the 11p and 11q loci, whereas those that were weakly or
      nontumorigenic were homozygous. Thus, the loss of one chromosome 11 with the
      duplication of another associated with the reduced tumorigenicity. Taken together
      with previous reports, our results indicate that a putative tumor suppressor gene
      on chromosome 11 controls tumorigenic expression in a gene dosage-dependent
      manner, and most importantly, suggested that the functional inactivation of the
      gene requires only a "one-hit" mutation.

PMID- 8548746
TI  - Peroxisome proliferators activate Kupffer cells in vivo.
AB  - The mechanism by which peroxisome proliferators increase cell replication and
      cause liver tumors in rodents remains unknown. When activated, Kupffer cells, the
      resident hepatic macrophages, release a variety of mitogenic stimuli that could
      theoretically increase cell proliferation in nearby hepatocytes. Therefore, in
      the present study we evaluated the effect of two potent peroxisome proliferators,
      nafenopin and WY-14,643, on Kupffer cell activation in vivo. Kupffer cell
      phagocytosis was determined continuously by monitoring rates of colloidal carbon
      uptake in the isolated, perfused liver after drug treatment in vivo. In the
      absence of peroxisome proliferators, colloidal carbon increased rates of oxygen
      uptake from 88 +/- 10 to 110 +/- 11 mumol/g/h. Livers from rats treated with
      either nafenopin (2-24 h) or WY-14,643 (24 h) were perfused for approximately 15
      min with Krebs-Henseleit buffer and then with buffer containing colloidal carbon
      (2 mg/ml). Five h after nafenopin treatment (100 mg/kg i.g.), basal rates of
      colloidal carbon uptake of 136 +/- 12 mg/g/h were increased to 188 +/- 12 and
      remained elevated after 24 h (203 +/- 3 mg/g/h). Nafenopin also increased rates
      in a dose-dependent manner (one-half-maximal response, approximately 75 mg/kg).
      Similarly, WY-14,643 elevated rates of colloidal carbon uptake 1.8-fold over
      controls. Functional parameters of Kupffer cells were also affected. For example,
      WY-14,643 increased plasma nitrite significantly. This study demonstrates clearly
      that nafenopin and WY-14,643 activate Kupffer cell phagocytosis, suggesting a
      role for cell-to-cell communication in the stimulation of cell replication by
      peroxisome proliferators.

PMID- 8548747
TI  - Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2
      phenylaminopyrimidine derivative.
AB  - Oncogenic activation of Abl proteins due to structural modifications can occur as
      a result of viral transduction or chromosomal translocation. The tyrosine protein
      kinase activity of oncogenic Abl proteins is known to be essential for their
      transforming activity. Therefore, we have attempted to identify selective
      inhibitors of the Abl tyrosine protein kinase. Herein we describe an inhibitor
      (CGP 57148) of the Abl and platelet-derived growth factor (PDGF) receptor protein
      tyrosine kinases from the 2-phenylaminopyrimidine class, which is highly active
      in vitro and in vivo. Submicromolar concentrations of the compound inhibited both
      v-Abl and PDGF receptor autophosphorylation and PDGF-induced c-fos mRNA
      expression selectively in intact cells. In contrast, ligand-induced growth factor
      receptor autophosphorylation in response to epidermal growth factor (EGF),
      insulin-like growth factor-I, and insulin showed no or weak inhibition by high
      concentrations of CGP 57148. c-fos mRNA expression induced by EGF, fibroblast
      growth factor, or phorbol ester was also insensitive to inhibition by CGP 57148.
      In antiproliferative assays, the compound was more than 30-100-fold more potent
      in inhibiting growth of v-abl-transformed PB-3c cells and v-sis-transformed
      BALB/c 3T3 cells relative to inhibition of EGF-dependent BALB/MK cells,
      interleukin-3-dependent FDC-P1 cells, and the T24 bladder carcinoma line.
      Furthermore, anchorage-independent growth of v-abl- and v-sis-transformed BALB/c
      3T3 cells was inhibited potently by CGP 57148. When tested in vivo, CGP 57148
      showed antitumor activity at tolerated doses against tumorigenic v-abl- and v-sis
      transformed BALB/c 3T3 cells. In contrast, CGP 57148 had no antitumor activity
      when tested using src-transformed BALB/c 3T3 cells. These findings suggest that
      CGP 57148 may have therapeutic potential for the treatment of diseases that
      involve abnormal cellular proliferation induced by Abl protein-tyrosine kinase
      deregulation or PDGF receptor activation.

PMID- 8548748
TI  - Lisofylline inhibits transforming growth factor beta release and enhances
      trilineage hematopoietic recovery after 5-fluorouracil treatment in mice.
AB  - The effectiveness of endogenous or exogenously administered colony-stimulating
      factors may be modulated by the presence of hematopoietic inhibitory molecules.
      Cytotoxic therapy may result in the induction of hematopoietic inhibitors
      contributing to prolonged myelosuppression, whereas preventing the induction of
      such inhibitors may accelerate multilineage recovery. Lisofylline [LSF; (R)-1-(5
      hydroxyhexyl)-3,7, dimethyl-xanthine], inhibits the signaling and/or release of
      certain hematopoietic inhibitory molecules such as tumor necrosis factor alpha,
      macrophage inflammatory protein 1 alpha, transforming growth factor beta, and IFN
      gamma. Treatment of murine bone marrow cells with the cytotoxic agent 5
      fluorouracil (5-FU) results in the release of a nondialyzable inhibitor of
      progenitor (colony-forming unit-granulocyte macrophage; CFU-GM) proliferation.
      When murine bone marrow cells were treated with 5-FU plus LSF, release of this
      inhibitor of CFU-GM proliferation was blocked. Neutralizing antibody and Western
      blot analysis indicated that the inhibitor was TGF-beta. We tested the effect of
      LSF (100 mg/kg i.p., b.i.d.) on multilineage regeneration after high-dose 5-FU or
      thiotepa treatment in BALB/c mice. In 4 of 5 experiments, LSF significantly
      accelerated neutrophil recovery (P < or = 0.05, Wilcoxon paired-signed test). In
      addition, platelet, reticulocyte, and CFU-GM regeneration were significantly
      accelerated in mice treated with LSF compared to control mice (P < or = 0.05).
      LSF had no significant effects on the ability of 5-FU to kill hematopoietic
      progenitor cells, nor did LSF stimulate or inhibit proliferation of CFU-GM. LSF
      had no effect on chemotherapy-induced killing of tumor cells in vitro, nor on the
      antitumor activity of 5-FU or thiotepa in BALB/c mice implanted with P388
      leukemia cells. Inhibition of hematopoietic inhibitor release may accelerate
      multilineage recovery after cytotoxic therapy and, as such, may represent an
      alternative or additional therapy to the use of positively acting lineage
      specific colony-stimulating factors.

PMID- 8548749
TI  - B7.1 expression on tumor cells circumvents the need of professional antigen
      presentation for in vitro propagation of cytotoxic T cell lines.
AB  - In vitro propagation of tumor-specific CTLs, to be used for identification of
      tumor antigens (Ag) and/or adoptive immunotherapy, is hampered by the need of
      large amounts of professional antigen-presenting cells (APC) used for periodical
      cycles of restimulation. We evaluated whether RMA T lymphoma cells, stably
      transfected with the cDNA encoding for the B7.1 costimulatory molecule, provided
      the activation signals to CD8+ T lymphocytes in the absence of professional APC
      and CD4+ helper cells. We demonstrate here that long-term CD8+ cell lines can be
      efficiently propagated in vitro by repeated cycles of stimulation with tumor
      cells stably expressing B7.1. Professional APC and CD4+ helper cells are not
      required as far as interleukin 2 is exogenously provided. Furthermore, CD8+
      blasts needed both signal 1 (Ag in the contest of the MHC molecule) and signal 2
      (interaction of costimulatory molecules) for restimulation. T cell blasts in the
      presence of signal 1 or 2 only still retained their effector potential but did
      not undergo clonal expansion. These results are very promising for further
      applications of specific immunotherapies in humans.

PMID- 8548750
TI  - Binding characteristics and antitumor properties of 1A10 bispecific antibody
      recognizing gp40 and human transferrin receptor.
AB  - The bispecific murine monoclonal antibody (MAb) 1A10 has specificity for the
      human transferrin receptor (TfR) and the human tumor-associated antigen gp40.
      This antibody, therefore, functions as an "antigen fork" by binding to two
      distinct antigens on the same malignant cell. Highly purified 1A10 inhibits the
      growth of cells coexpressing high levels of human TfR and the tumor-associated
      antigen gp40 by binding to both target antigens. In SW948 cells, the majority of
      1A10 binding is via its gp40 specificity, and half-maximal inhibition of cell
      growth by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      requires 20-30-micrograms/ml concentrations of 1A10. The binding of 1A10
      correlates with growth inhibition in the cell lines HT-29, SK-OV-3, OVCAR-2, and
      OVCAR-3. The growth of OVCAR-10 cells, which express little gp40 and TfR, is not
      inhibited by 1A10. However, SK-BR-3 cells, which express abundant gp40 and
      extremely high levels of TfR, are insensitive to the effects of 1A10. In some
      cell lines, combined exposure to 1A10 and the iron chelator deferoxamine mesylate
      has synergistic antiproliferative effects. A single i.p. dose of 600 micrograms
      1A10 is sufficient to achieve an estimated tumor concentration of at least 30
      micrograms/ml for 7 days in C.B17/Icr-scid mice bearing SW948 human tumor
      xenografts. Treatment of scid mice bearing day 2 or day 4 SW948 xenografts with
      single or multiple 1A10 doses inhibits tumor growth in a dose-related fashion.
      Antitumor effects are not seen with therapy using either parental antibody of
      1A10. The antiproliferative properties of 1A10 in tumor cells overexpressing gp40
      and TfR suggest avenues for the development of new bispecific antibody-promoted
      treatment strategies.

PMID- 8548751
TI  - Autoimmunity to collagen in human lung cancer.
AB  - Autoantibodies have been described in human cancer patients as well as in animal
      models of malignancy. The extracellular matrix and especially basement membranes
      act as barriers for tumor cell invasion. Collagen, particularly types I, III, and
      IV, are major constituents of the extracellular matrix. We tested the hypothesis
      that autoimmunity to collagen antigens is present in lung cancer. Sera from 67
      patients with lung cancer and 50 reference subjects were tested for anticollagen
      antibodies by using purified human collagen types I-V and for antibodies binding
      human cartilage aggrecan proteoglycan. Antibody levels were determined by using
      ELISA. The relationship of serum levels of these antibodies to patient survival,
      histology, treatment response, disease stage, and pack years of smoking was
      examined by using multiple regression and discriminant function analyses. A
      subgroup of 45 patients in whom a smoking history was available was analyzed
      separately. Within 1 month of the initiation of therapy, mean serum levels of
      antibodies binding fibrillar collagen types I-III and V were significantly higher
      (P < 0.025) than were those in control sera (43.2% of patients positive for one
      or more anticollagen antibodies). Antibodies binding aggrecan proteoglycan were
      not different between patients and control sera. In the lung cancer patients, the
      levels of serum antibodies binding types IV and V collagens contributed to the
      variance of progression-free survival days, survival days, and the duration of
      favorable response in opposite directions. Histological cell type contributed to
      the variance in the level of serum antibody binding collagen types IV and V.
      Lower levels of antibody binding type IV and higher levels of antibody binding
      type V were associated with small cell carcinoma. The pack-years of smoking only
      contributed to the variance in the level of serum antibody binding type V
      collagen. We conclude that autoantibodies to fibrillar collagen antigens are
      present frequently in lung cancer patients, and their levels may be related to
      histological cell type and to the duration of the response to treatment.

PMID- 8548752
TI  - Tumor target binding induces phosphorylation of two M(r) 65,000 lymphokine
      activated killer proteins.
AB  - Effector-target cell conjugate formation is an essential step during lymphokine
      activated killer (LAK) cell-mediated cytotoxicity. Protein phosphorylation
      changes in human LAKs after contact with NK-resistant (LAK-sensitive) tumors were
      examined by two-dimensional SDS-PAGE. Exposure to either SK-Mel-1 (melanoma) or
      Raji (lymphoma) targets led to increased phosphorylation of two M(r) 65,000 LAK
      proteins, pp65a and pp65b, with isoelectric points of 5.1 and 5.2, respectively.
      Phosphorylation of both substrates was initiated between 1 and 5 min after
      coincubation with tumor targets. Contact between LAKs and targets was required
      for p65 phosphorylation because soluble tumor factors failed to induce
      phosphorylation. Normal peripheral blood lymphocyte targets, which are bound very
      poorly by LAKs and are resistant to killing, failed to induce LAK p65
      phosphorylation. The broad protein kinase inhibitor staurosporine inhibited
      phosphorylation of pp65a and pp65b, supporting the hypothesis that activation of
      a LAK protein kinase leads to p65 phosphorylation. Cross-linking of CD16 (Fc
      gamma RIIIA), which mediates antibody-dependent cellular cytotoxicity in LAKs,
      also led to increased pp65a and pp65b phosphorylation. Collectively, these data
      provide correlative evidence that p65 phosphorylation may be involved in the
      cytolytic function of LAKs.

PMID- 8548753
TI  - Characterization of the M(r) 65,000 lymphokine-activated killer proteins
      phosphorylated after tumor target binding: evidence that pp65a and pp65b are
      phosphorylated forms of L-plastin.
AB  - Contact between lymphokine-activated killer (LAK) cells and natural killer
      resistant tumor targets SK-Mel-1 (human melanoma) or Raji (human lymphoma)
      stimulates phosphorylation of two M(r) 65,000 LAK proteins (pp65a and pp65b) with
      nearly identical isoelectric points. Phosphoamino acid analysis of pp65a and
      pp65b detected phosphorylation exclusively on serine residues. Phosphotyrosine
      could not be detected on either substrate after immunoblotting with an
      antiphosphotyrosine antibody, and herbimycin A treatment failed to inhibit p65
      phosphorylation induced by target contact. However, phorbol myristate acetate
      treatment alone induced LAK pp65a and pp65b phosphorylation, suggesting
      phosphorylation may be mediated by protein kinase C or a protein kinase C
      regulated kinase. The molecular weight and isoelectric points of pp65a and pp65b
      are similar to that reported for the human actin-bundling protein, L-plastin (L
      fimbrin). On two-dimensional SDS-PAGE gel immunoblots, a peptide specific anti-L
      plastin antiserum bound to pp65a and pp65b, suggesting that the phosphoproteins
      are similar or identical to L-plastin. In addition, two adjacent M(r) 65,000 LAK
      proteins were also detected by the antiserum and may correspond to
      unphosphorylated forms of L-plastin. On the basis of known properties of
      phosphorylated L-plastin, it is hypothesized that p65 phosphorylation in LAKs may
      regulate adhesion to tumor targets.

PMID- 8548754
TI  - Tumor necrosis factor-alpha allelic frequency and chromosome 6 allelic imbalance
      in patients with colorectal cancer.
AB  - The human tumor necrosis factor (TNF) locus is located on chromosome 6p21.3 and
      contains at least five polymorphic microsatellites. In this study, we compared
      the allelic frequencies derived from 50 normal controls to 64 patients with
      colorectal cancer at one of these loci, TNF alpha. No differences in allelic
      frequencies were observed between these two groups (P = 0.47). However,
      sequencing of the TNF alpha PCR product revealed two populations of TNF alpha
      alleles; alleles with the expected DNA sequence (i.e., the expected number of
      AC/GT repeats) and alleles that contained 8-bp deletions adjacent to the
      microsatellite repeat. In addition, we also examined paired normal and tumor DNA
      from the colorectal cancer group for microsatellite alterations at the TNF alpha
      locus, including allelic loss of heterozygosity and microsatellite instability.
      Of the 64 tumors examined, 13 (20%) demonstrated microsatellite instability, and
      14 (42%) of 33 informative cases demonstrated allelic imbalance. Analysis of 10
      additional chromosome 6 loci for allelic loss showed that 23 (47%) of 49
      informative cases exhibited allelic imbalance with at least one chromosome 6p
      marker, 23 (47%) of 49 with at least one 6q marker, and 29 (59%) of 49 with at
      least one marker on chromosome 6. Examination of tumors for the minimal region of
      deletion overlap suggests the presence of tumor suppressor genes on both 6p and
      6q.

PMID- 8548755
TI  - CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are
      inversely correlated.
AB  - p16 is involved in a cell cycle regulatory cascade that includes cyclin-dependent
      kinase 4 (cdk4), cyclin D1, and pRb (retinoblastoma). Alterations of each of
      these components have been described in primary human glioblastoma multiforme
      (GBM) or in GBM cell lines. Because perturbation of any component in this pathway
      may have similar oncogenic effects, we studied the relationship between
      abnormalities of CDKN2/p16 and RB, the two commonly involved tumor suppressor
      genes, in 55 astrocytic gliomas (42 GBMs, 8 anaplastic astrocytomas, and 5
      astrocytomas). By using comparative multiplex PCR, homozygous deletions of the
      CDKN2/p16 gene were detected in 24 GBMs (57%) and in 2 anaplastic astrocytomas.
      Two additional GBMs and one anaplastic astrocytoma had allelic loss of chromosome
      9p, as assessed by microsatellite polymorphisms flanking the CDKN2/p16 region.
      Single-strand conformation polymorphism and DNA sequencing analysis of all three
      coding exons of CDKN2/p16 revealed a frameshift mutation (four-bp deletion) in
      one of the three GBMs that had lost the remaining 9p allele. Allelic loss of
      chromosome 13q at the RB gene, RB gene mutations, or loss of pRb expression was
      noted in 14 GBMs (33%) and 2 anaplastic astrocytomas. Thirty-six of 42 GBMs (86%)
      had alterations of either CDKN2/p16 (n = 22), RB (n = 10), or both (n = 4); these
      two genetic changes, however, were relatively exclusive (P = 0.003). Furthermore,
      of the six GBMs without either CDKN2/p16 or RB gene abnormalities, one case had
      CDK4 gene amplification. These data indicate that the vast majority of GBMs
      probably have inactivation of the p16-cdk4/cyclin D1-pRb pathway. The findings
      also provide corroborative evidence that CDKN2/p16 and RB are the critical glioma
      tumor suppressor genes on chromosomes 9p and 13q, respectively.

PMID- 8548756
TI  - Measurement of radiation-induced damage in human glioma cells with flow
      cytometry.
AB  - Using flow cytometry, we studied DNA supercoiling changes in human glioma cell
      line SF-126 after irradiation. To release nucleoids (dehistonized DNA in a
      supercoiled form attached to the nuclear matrix), cells were lysed in a high-salt
      buffer. Radiation-induced changes in nucleoids were measured by flow cytometry as
      changes in forward light scatter. Propidium iodide titration curves showed that
      rewinding of DNA supercoils in irradiated cells was inhibited. To optimize the
      experimental conditions, we analyzed the effect of lysis time and nucleoid size
      distribution within the sample. Under optimal conditions, changes in nucleoids
      were detected after radiation doses as low as 0.5 Gy. The repair of radiation
      induced damage in nucleoids followed biphasic kinetics; 50% of the damage was
      repaired within about 5 min, and the remainder within about 30 min.
      Interestingly, irradiated S-phase cells showed less damage, as measured by this
      assay, than irradiated G1- or G2-phase cells, which is consistent with the
      relative radioresistance of S-phase cells as measured with cell survival assays.
      Our findings show that flow cytometric measurement of supercoiling changes is a
      sensitive and relatively rapid method for quantitating radiation-induced damage
      in individual cells.

PMID- 8548757
TI  - An engineered four-stranded coiled coil substitutes for the tetramerization
      domain of wild-type p53 and alleviates transdominant inhibition by tumor-derived
      p53 mutants.
AB  - The tetramerization domain of p53 is required for efficient tumor suppressor
      activity. This domain, however, also allows wild-type p53 to heterooligomerize
      with dominant negative tumor-derived p53 mutants. We explored the feasibility of
      substituting the native tetramerization domain of wild-type p53 with an
      engineered leucine zipper that assembles as a four-stranded coiled coil. The
      engineered zipper drove p53 tetramerization in vitro and p53 function in vivo.
      Furthermore, it alleviated transdominant inhibition by tumor-derived p53 mutants,
      implying that dominant negative mutants act by hetero-oligomerizing with wild
      type p53. The ability of the engineered zipper to drive tetramerization was
      critical for p53 function, since p53 dimers, formed by substituting the p53
      tetramerization domain with a native leucine zipper, were weak tumor suppressors.

PMID- 8548758
TI  - MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor
      infiltrating lymphocytes from a patient with breast cancer: characterization and
      antigen-specific activation.
AB  - A potential target for development of tumor-specific immunotherapeutic strategies
      is the MAGE-1 gene. We have utilized a recently developed recombinant canarypox
      (ALVAC) virus vector containing the MAGE-1 gene (vCP235) to activate CTLs from a
      breast cancer patient bearing a MAGE-1+ tumor. Tumor-infiltrating lymphocytes
      (TILs) obtained from the tumor of a patient were stimulated in vitro with
      irradiated autologous peripheral blood mononuclear cells acutely infected with
      the vCP235 construct. These TILs preferentially expanded approximately 6-fold
      over a 16-day culture period and specifically recognized an allogeneic
      transformed B-cell line acutely infected with a vaccinia-MAGE-1 recombinant
      targeting vector (vP1188) in the context of HLA-A2 and/or B7. TCR V beta analysis
      of in vitro expanded T cells by a quantitative multiprobe RNase protection assay
      revealed preferential expansion of TCR V beta 6.3 and V beta 6.4. In addition,
      homologous T-cell receptor beta CDR3 joining sequences were found in the in vitro
      stimulated cultures. These results suggest that tumor antigen-specific, MHC
      restricted CTLs may be derived from precursor CTLs present in TILs obtained from
      patients with MAGE-1+ tumors by in vitro stimulation with recombinant avipox MAGE
      1 virus-infected autologous cells. Collectively, these findings provide a
      rationale for tumor-associated antigen-based immunization as a means of
      activating precursor CTLs residing in patients with tumors expressing defined
      tumor-associated antigens such as MAGE-1.

PMID- 8548759
TI  - Association of loss of heterozygosity on chromosome 17p with high platelet
      derived growth factor alpha receptor expression in human malignant gliomas.
AB  - The aim of this study was to examine platelet-derived growth factor alpha
      receptor (PDGFR-alpha) expression in gliomas of various degrees of malignancy and
      to correlate the findings with genetic alterations present in the same tumor
      samples. We analyzed 83 tumors by in situ hybridization using a PDGFR-alpha cRNA
      probe. Increased PDGFR-alpha mRNA expression was observed in astrocytic tumors of
      all stages of malignancy, although the highest levels were found in glioblastoma
      multiforme. To evaluate the frequency of PDGFR-alpha gene amplification,
      differential PCR requiring less DNA than Southern analysis was used with
      fluorescence-labeled primers corresponding to the kinase insert region of the
      PDGFR-alpha. Only 7 of 43 glioblastomas and none of the other tumors tested
      showed amplification of the PDGFR-alpha gene, suggesting that a mechanism other
      than gene amplification is responsible for the overexpression of PDGFR-alpha in
      glial brain tumors. Comparison of the in situ hybridization data with genetic
      alterations in the same tumor material showed a significant correlation of loss
      of heterozygosity on chromosome 17p (Fisher's exact, P < 0.0002) with high
      expression levels of PDGFR-alpha. Because that was the case in both low- and high
      grade astrocytomas, our data imply that PDGFR-alpha is actively involved in tumor
      cell proliferation in early and late stages of glioma development. The
      association of PDGFR-alpha expression with a distinct subset of glioblastomas
      characterized by loss of heterozygosity 17p further supports the differentiation
      of these tumors into molecular variants.

PMID- 8548760
TI  - Expression of vascular permeability factor/vascular endothelial growth factor by
      melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.
AB  - Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is
      an angiogenic cytokine expressed by many human and animal tumors. Hypoxia often
      up-regulates VPF/VEGF expression further. To better define the role of VPF/VEGF
      in tumor biology, we screened tumorigenic lines for those expressing minimal
      constitutive and hypoxia-inducible VPF/VEGF. Human melanoma SK-MEL-2 cells best
      fit these criteria and formed small, poorly vascularized tumors in
      immunodeficient mice. We transfected SK-MEL-2 cells stably with sense or
      antisense mouse VPF/VEGF cDNA or with vector alone. Cells transfected with sense
      VPF/VEGF (V+) expressed and secreted large amounts of mouse VPF/VEGF and formed
      well-vascularized tumors with hyperpermeable blood vessels and minimal necrosis
      in nude/SCID mice. Antisense-transfected VPF/VEGF (V-) cells expressed reduced
      constitutive VPF/VEGF and no detectable mouse VPF/VEGF, and formed small,
      minimally vascularized tumors exhibiting extensive necrosis. Vector-alone
      transfectants (N1 cells) behaved like parental cells. V+ cells formed numerous
      lung tumor colonies in SCID mice, approximately 50-fold more than N1 cells,
      whereas V- cells formed few or none. These experiments demonstrate that VPF/VEGF
      promotes melanoma growth by stimulating angiogenesis and that constitutive
      VPF/VEGF expression dramatically promotes tumor colonization in the lung.

PMID- 8548761
TI  - Tenascin-C expression by angiogenic vessels in human astrocytomas and by human
      brain endothelial cells in vitro.
AB  - The expression of the extracellular matrix glycoprotein tenascin-C (TN) is
      enhanced in human astrocytomas and correlates with angiogenesis. To determine
      whether vascular cells are able to synthesize TN, we investigated the expression
      of TN protein and mRNA in nine astrocytomas. Immunogold electron microscopy in
      two glioblastomas multiforme detected the presence of TN in an extracellular
      perivascular location and to a lesser extent among tumor cells, confirming light
      microscopy immunohistochemical findings. In situ hybridization of astrocytomas
      using a digoxigenin-labeled antisense riboprobe detected strong staining for TN
      mRNA in vascular cells, especially in hyperplastic vessels, including those at
      the invasive edge of the tumors but not in vessels of normal brains. We observed
      weaker staining in tumor cells indicating a higher level of TN mRNA in vascular
      than in tumor cells. No staining was detected with the sense probe. Moreover, we
      investigated the ability of human brain microvessel endothelial cells (HBMECs) in
      primary culture to synthesize TN in vitro. Western blot analysis of the culture
      supernatants from HBMECs detected large amounts of TN. Immunogold silver staining
      demonstrated the presence of TN on the surface of HBMECs and in the
      subendothelial matrix. The distribution of TN mRNA in vascular cells of
      astrocytomas and the ability of HBMECs to synthesize TN in vitro demonstrate that
      vascular cells, including endothelial cells, are a major source of TN associated
      with angiogenesis. Furthermore, our results suggest that TN expression may be
      associated with endothelial cell activation and may play an important role in
      angiogenesis.

PMID- 8548762
TI  - Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV
      collagenases in colorectal cancer.
AB  - Using quantitative zymography, we measured activity of the type IV collagenases
      metalloprotease 2 (MMP-2) and MMP-9 in 192 biopsies from colorectal carcinomas,
      adenomas, and normal bowel. The median level of MMP-9 in samples from Dukes'
      stage A (n = 18) or C (n = 48) tumors was significantly higher than in stage B
      carcinomas (n = 65), adenomas (n = 25), and normals (n = 36; P = 0.0001). The
      median level of active MMP-2 was significantly higher in stage A or C compared
      with adenomas (P = 0.0001) and normals (P = 0.0001). The median level of inactive
      MMP-2 was higher in all Dukes' stages compared with normals and adenomas (P =
      0.0001). There was a significant increase in inactive MMP-2 from Jass prognostic
      groups I-IV (P = 0.006) but no correlation with the active enzyme. MMP activity
      was not related to tumor differentiation, colon versus rectal location, or
      disease-free, 5-year survival. All groups expressed mRNA for both enzymes, but
      there were quantitative and locational differences in MMP-2 mRNA expression
      between normal, benign, and malignant tissues. Thus MMP-2 is controlled at the
      level of mRNA and protein production and activation in colorectal cancer, and
      active MMP-2 and MMP-9 enzymes are associated strongly with Dukes' A and C stages
      of the disease. Variations in MMP levels with the stage or prognostic group of
      colorectal cancer reflect their differing stromal content.

PMID- 8548763
TI  - Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity
      and human papilloma virus tumor status.
AB  - Specific human papilloma virus (HPV) types appear to be necessary etiological
      factors for most cervical cancers, yet additional genetic alterations seem to be
      required for their development and progression. The aim of this study is to
      determine the likely chromosomes location of tumorigenicity suppressor-like
      genes, the loss of function of which might be important in the origin or
      progression of cervical carcinomas. PCR with primers for 75 highly polymorphic
      microsatellite loci located on the major autosome arms were used to estimate the
      incidence of loss of heterozygosity (LOH) in 38 tumors. The HPV status of the
      tumors was also determined. LOH was found to involve 19 chromosome arms in 20-43%
      of the tumors. Chromosome arms 6p, 3p, and 18q are most frequently involved in
      LOH in 43, 39, and 35% of the informative carcinomas, respectively. The
      respective regions involved are 6p21.1-23, 3p13-25.3, and 18q12.2-21.2. LOH is
      generally limited to specific band segments within these regions. Similar high
      incidences of LOH of the same 3p segments have been reported in cervical
      carcinomas from different parts of the world. The same 3p and 6p segments are
      involved in many types of common cancers, whereas 18q changes are less frequent
      in other cancers. Chromosome arms 1q, 2q, 3q, 4p, 4q, 5p, 5q, 6q, 7q, 8p, 8q,
      11q, 13q, 16p, 18p, and 19p are involved in LOH in 20-33% of the cervical tumors.
      Chromosome 11 alterations are among the most frequently found in many different
      types of neoplasias. In this study, 11p was involved in 16% of the tumors, and
      11q was involved in 22%. Chromosome 17 alterations are found in more cancers than
      those of any other chromosome, frequently involving the p53 gene on 17p. LOH of
      17p was found in 5 (15%) cervical tumors; 2 of these were HPV negative and
      expressed mutant p53. In such HPV-negative tumors, direct mutation of the wild
      type p53 appears to replace the inactivation of the p53 product by oncogenic HPV
      types. Tumors with LOH at many loci were, on the average, at more advanced
      stages, as were tumors with mutant p53. The higher overall incidence of LOH in
      cervical carcinomas as compared to other cancers, and the diversity of LOH
      patterns found, suggest that different cervical carcinomas probably arise and/or
      progress, in part, because of the loss of function of different yet finite sets
      of tumorigenicity suppressor genes and genes that are involved in tumor
      progression and metastasis. The findings also indicate that certain chromosome
      segments that are often altered in cervical carcinomas are also frequently
      altered in several other types of cancers. It remains to be determined whether
      the same or different genes located within these segments are involved in the
      different cancer types.

PMID- 8548764
TI  - Correlations between intrinsic chemoresistance and HER-2/neu gene expression, p53
      gene mutations, and cell proliferation characteristics in non-small cell lung
      cancer cell lines.
AB  - Using a panel of 20 non-small cell lung cancer (NSCLC) cell lines established
      from previously untreated patients, we investigated the relationships between
      intrinsic chemoresistance (to four agents used commonly in the therapy of NSCLC)
      and HER-2/neu gene expression (which encodes glycoprotein p185neu), p53 gene
      mutations, and cell proliferation characteristics. Our results demonstrated that
      high p185neu expression was correlated with chemoresistance, low S-phase
      fractions, and long doubling times. By contrast, cell lines expressing relatively
      low levels of p185neu were relatively chemosensitive and had higher S-phase
      fractions and shorter doubling times. Although mutation of the p53 gene was a
      common event in this panel of cell lines (present in 18 of 20 lines), there was
      no relationship between mutations at any specific codon and chemoresistance or
      cell proliferation characteristics. Multivariate analysis revealed that the level
      of p185neu was the only independent predictor for chemoresistance to doxorubicin,
      etoposide, and probably cisplatin. Although intrinsic chemoresistance almost
      certainly is a multifactorial process, overexpression of p185neu may be an
      important factor in the chemoresistance of NSCLC.

PMID- 8548765
TI  - Treatment of established tumors with a novel vaccine that enhances major
      histocompatibility class II presentation of tumor antigen.
AB  - Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is
      critical to the generation of antitumor immunity. In an attempt to enhance MHC
      class II antigen processing, we linked the sorting signals of the lysosome
      associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma
      virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1). Previously, we
      found that expression of this chimera in vitro and in vivo with a recombinant
      vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced
      MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild
      type E7. In the current study, we tested these recombinant vaccinia for in vivo
      protection against an E7+ tumor, TC-1, which was derived from primary epithelial
      cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes.
      All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia
      showed progressive tumor growth when challenged with a tumorigenic dose of TC-1
      tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1
      vaccinia remained tumor free 3 months after tumor injection. Furthermore,
      treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small
      established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on
      this established tumor burden. These findings point out the therapeutic
      limitations of recombinant vaccinia expressing unmodified tumor antigens.
      Further, they demonstrate that modifications that reroute a cytosolic tumor
      antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo
      therapeutic potency of recombinant vaccines.

PMID- 8548766
TI  - Modulation of prostaglandin A1-induced thermotolerance by quercetin in human
      leukemic cells: role of heat shock protein 70.
AB  - Prostaglandins of the A type (PGAs) function as signals for heat shock protein
      (hsp) synthesis in mammalian cells. In human K562 erythroleukemic cells, PGA1
      induces the synthesis of a M(r) 70,000 hsp (hsp70) by cycloheximide-sensitive
      activation of heat shock transcription factor (HSF). Induction of hsp70 has been
      associated recently with the ability of PGA to protect K562 cells from thermal
      injury, establishing a thermotolerant state; however, the role of hsp70 in
      thermotolerance is still controversial. Because quercetin was shown to modulate
      hsp70 expression after heat shock in K562 cells, we have investigated the effect
      of this flavonoid on HSF activation, hsp70 synthesis, and thermotolerance in
      human K562 cells after induction with PGA1. Quercetin was found to inhibit hsp70
      synthesis for a period of 3-6 h after PGA1 treatment. This transient block was
      exerted at the transcriptional level and was not due to the loss of HSF DNA
      binding activity. After the initial delay, hsp70 synthesis reached the same rate
      as the PGA1-treated control, and it was actually prolonged in the presence of
      quercetin. In PGA1-treated cells, quercetin suppressed PGA1-induced
      thermotolerance completely if the heat shock was applied at a time (6 h) when
      hsp70 synthesis was inhibited, whereas it could not prevent the establishment of
      a thermotolerant state if the heat challenge was applied 24 h after treatment,
      when hsp70 synthesis was not affected. These results support strongly the
      hypothesis that hsp70 is involved in the establishment of thermotolerance in
      human cells.

PMID- 8548767
TI  - Telomerase activity: a prevalent marker of malignant human prostate tissue.
AB  - We urgently need biochemical markers to detect the malignant nature and
      pathological states of the human prostate. We report that telomerase activity is
      associated with prostate cancer but absent in the benign disease and normal
      gland. Telomerase is, therefore, a potential diagnostic marker for prostate
      cancer. Twenty-five human prostates resected at the time of radical prostatectomy
      were dissected to obtain matched adjacent areas of normal, central zone benign
      prostatic hyperplasia (BPH), and pathologically confirmed cancer tissue. These
      matched tissue samples were assayed for telomerase activity using a sensitive PCR
      technique. None of the normal tissues exhibited telomerase activity. In contrast,
      21 of the 25 (84%) cancers were strongly positive. At the time of prostatectomy,
      four lymph nodes were positive for metastases and all were strongly positive for
      telomerase activity. In adjacent BPH tissues taken from the cancerous prostates,
      only 3 of the 25 tissues (12%) were weakly positive. Telomerase activity was not
      detected in ten BPH samples recovered from patients who underwent open surgery
      solely for BPH. All five available cell lines of human prostate cancer (DU145,
      LNCaP, PC3, PPC1, and TSU) were strongly positive. Short telomere lengths have
      been observed in several human cancers. We also measured the telomere lengths in
      27 matched samples of normal, BPH, and cancer tissue taken from nine radical
      prostatectomies. The telomeres from cancer tissue were significantly and
      consistently shorter than either the adjacent normal or adjacent BPH tissues. Our
      results indicate that telomerase activity, as well as telomere lengths, may be
      markers for distinguishing prostate cancer from normal and benign prostate
      tissues.

PMID- 8548768
TI  - Genetic aberrations detected by comparative genomic hybridization are associated
      with clinical outcome in renal cell carcinoma.
AB  - The clinical behavior of renal cell carcinoma (RCC) cannot be predicted by
      histological and other markers. In this study, comparative genomic hybridization
      was used to evaluate whether the number of genomic aberrations has prognostic
      significance in 41 nonmetastatic clear cell RCC extending beyond the renal
      capsule. Losses were most prevalent at 3p (56%) and 9p and 13q (24% each). The
      number of DNA losses per tumor was associated with recurrence-free survival (P =
      0.03). DNA gains most often involved chromosome 5q (17%) and chromosome 7 (15%).
      The number of DNA gains was not associated with clinical outcome. Loss of
      chromosome 9p was the only individual locus associated with recurrence (P =
      0.04), suggesting that a tumor suppressor gene on chromosome 9p may play a role
      in RCC progression.

PMID- 8548769
TI  - Regulation of p21WAF1/CIP1 expression through mitogen-activated protein kinase
      signaling pathway.
AB  - p21WAF1/CIP1 is a cyclin-dependent kinase inhibitor whose expression in mammalian
      tissues is highly induced in response to stress as well as during normal
      development and differentiation. Induction of p21WAF1/CIP1 in response to DNA
      damage occurs through a transcriptional mechanism that is dependent on the
      activation of the tumor suppressor protein p53. Recent evidence indicates that
      p21WAF1/CIP1 can also be induced independently of p53, but the signal
      transduction mechanisms involved in regulating p21WAF1/CIP1 expression in these
      situations have not been elucidated. In this study, we have addressed the role of
      the mitogen-activated protein kinase signaling pathway in the induction of
      p21WAF1/CIP1 in response to growth factor treatment. Using an experimental
      approach involving cotransfection of a p21WAF1/CIP1 promoter-luciferase construct
      with a variety of plasmids expressing dominant positive or dominant negative
      mutant proteins involved in this signaling pathway, we provide evidence to
      support a role for mitogen-activated protein kinase in the transcriptional
      activation of p21WAF1/CIP1 by growth factor stimulation.

PMID- 8548770
TI  - Overexpression of cyclin D1 enhances gene amplification.
AB  - Defects in cell cycle control and increased genomic instability, including gene
      amplification, often occur during cancer development. Cyclin D1 plays a pivotal
      role in G1, and this gene is frequently amplified and overexpressed in several
      types of human cancer. This study demonstrates that ectopic overexpression of
      cyclin D1 in a rat liver epithelial cell line markedly increased the yield of
      cells containing amplified copies of the CAD gene. This effect was associated
      with a loss of G1-S checkpoint control, although the cyclin D1-overexpressing
      cells had a normal p53 gene. The capacity of cyclin D1 to enhance gene
      amplification may contribute to the process of genomic instability during tumor
      development.

PMID- 8548771
TI  - Expression of the Bcl-2 homologue Mcl-1 correlates with survival of peripheral
      blood B lymphocytes.
AB  - Normal peripheral blood B lymphocytes undergo spontaneous apoptosis in vitro, and
      this process is regulated positively and negatively by several immunomodulatory
      stimuli. We have shown previously that Bcl-2 protein levels are unaltered by
      these factors, suggesting a Bcl-2-independent regulation of apoptosis in this
      system. Here, we have investigated the possibility that the three recently
      identified Bcl-2 homologues, Bax, Bcl-x, and Mcl-1, could be involved instead.
      Freshly isolated cells expressed both Bax and Mcl-1 protein, but only low levels
      of Bcl-xL and no detectable Bcl-xS, as determined by Western blot analysis. Upon
      culture of cells with apoptotic or survival stimuli, Bax and Bcl-xL protein
      levels remained relatively unchanged. By contrast, Mcl-1 levels decreased
      markedly in cells undergoing apoptosis in medium and, even more dramatically,
      after treatment with the apoptotic stimuli transforming growth factor beta 1 and
      forskolin. This decrease was rapid and preceded cell death. Furthermore, all the
      survival stimuli tested (interleukin 4, anti-IgM antibodies, and the phorbol
      ester 12-O-tetradecanoylphorbol-13-acetate) prevented the decline in Mcl-1
      levels. This striking correlation between cell survival and Mcl-1 expression in
      peripheral blood B cells suggests the possible involvement of Mcl-1, instead of
      Bcl-2, in the regulation of apoptosis in these cells. The present study is the
      first one linking this novel Bcl-2 homologue to the control of cell death in
      normal cells.

PMID- 8548772
TI  - Genetic change in transforming growth factor beta (TGF-beta) receptor type I gene
      correlates with insensitivity to TGF-beta 1 in human prostate cancer cells.
AB  - Transforming growth factor beta 1 (TGF-beta 1), a potential regulator of growth
      of prostate cancer cells, exerts its effects through interaction with membrane
      receptors. In the present study, an attempt was made to establish a correlation
      between TGF-beta 1 sensitivity and TGF-beta receptor expression in three prostate
      cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-beta 1
      inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF
      beta signals through a heteromeric complex composed of TGF-beta receptors type II
      and type I, the expression of these receptors was investigated by Western blot
      analysis and reverse transcriptase-PCR. These studies demonstrated that all three
      prostate cancer cell lines express type II receptor. In contrast, type I receptor
      was detected only in the TGF-beta 1-sensitive PC3 and DU145 cells but not in the
      TGF-beta 1-insensitive LNCaP cells. To investigate the possibility that the
      undetectable expression of type I receptor in LNCaP cells is due to a change in
      the respective gene, Southern blot analysis was performed. The result
      demonstrated that there was a genetic change in type I receptor gene in these
      cells. Subsequently, when LNCaP cells were transiently transfected with T beta R
      I cDNA, sensitivity to TGF-beta 1 was restored. These observations indicate that
      LNCaP cells contain a defective T beta R-I gene which rendered these cells
      insensitive to the action of TGF-beta 1.

PMID- 8548773
TI  - No evidence for mutations in the alpha- and beta-catenin genes in human gastric
      and breast carcinomas.
AB  - Disturbed function of E-cadherin and/or of one of its anchoring proteins, the
      catenins, is thought to destabilize E-cadherin-mediated cell-cell adhesion, which
      may enhance the invasiveness of epithelial cells and thus favor carcinoma
      progression. Reduced expression of E-cadherin and alpha-catenin, as well as
      mutations in the E-cadherin gene, have been found in various carcinomas, whereas
      mutations in the alpha- and beta-catenin genes have been described only in
      carcinoma cell lines. Using reverse transcription-PCR, followed by agarose gel
      electrophoresis and single-strand conformational polymorphism, we examined 16
      diffuse- and 5 intestinal-type gastric carcinomas, as well as 9 lobular and 2
      ductal breast carcinomas, for mutations of alpha- and beta-catenin cDNA. All of
      the investigated tumors were analyzed previously for E-cadherin mutations.
      Comparing tumorous and nontumorous samples, we detected neither deletions nor
      aberrant single-strand conformational polymorphism patterns. At nucleotide 2220
      of the alpha-catenin gene, we identified one frequent polymorphism. Our findings
      suggest that, in contrast to E-cadherin, mutations of alpha- and beta-catenin do
      not contribute to the pathogenesis or the diffuse growth patterns of gastric or
      breast carcinomas.

PMID- 8548774
TI  - Radiation-induced neoplastic transformation of human prostate epithelial cells.
AB  - We report the malignant transformation of human prostate epithelial cells (267B1)
      after multiple exposures to ionizing radiation. Carcinogenic progression of cells
      from immortal growth to anchorage-independent growth in soft agar to
      tumorigenicity in athymic mice resulted after a cumulative X-ray dose of 30 Gy.
      The tumors were characterized histologically as poorly differentiated
      adenocarcinomas, expressed prostate-specific antigen, and stained positive for
      keratin. No p53 or ras mutations were observed. Numerous chromosomal defects were
      noted on karyotypes after radiation exposure. However, chromosome 3 and 8
      translocations were observed predominantly in the tumor outgrowths. These
      findings provide the first evidence of malignant transformation of human prostate
      epithelial cells exposed to ionizing radiation.

PMID- 8548775
TI  - Tamoxifen metabolic activation: comparison of DNA adducts formed by microsomal
      and chemical activation of tamoxifen and 4-hydroxytamoxifen with DNA adducts
      formed in vivo.
AB  - One of our laboratories recently showed by 32P-postlabeling that administration
      of tamoxifen to mice induces two groups of hepatic DNA adducts comprising two
      major spots, nos. 3 and 5, respectively. 4-Hydroxytamoxifen and alpha
      hydroxytamoxifen appear to be the proximate metabolites of groups I and II
      adducts, respectively. The relative significance of these two adduct groups for
      tamoxifen carcinogenicity remains to be established. To determine the activation
      mechanism(s) of tamoxifen and 4-hydroxytamoxifen, in vivo adducts were compared
      by 32P-postlabeling with adducts generated by microsomal or chemical activation
      in vitro. Microsomal activation of 4-hydroxytamoxifen and tamoxifen,
      respectively, in the presence of DNA and cumene hydroperoxide, induced two
      adducts, which mapped similarly to the corresponding in vivo adduct spots 3 and
      5. Chemical oxidation of 4-hydroxytamoxifen with silver(II) oxide, followed by
      incubation of the product(s) with DNA, elicited the formation of a major spot
      (Q1), while tamoxifen itself did not react. Rechromatographic analyses revealed
      that in vitro fractions 3 and Q1 (from 4-hydroxytamoxifen) matched the major in
      vivo group I adduct fraction 3, consistent with the hypothesis that 4
      hydroxytamoxifen is a precursor for adduct fraction 3 in vivo. The in vitro
      adduct fraction 5 (from tamoxifen) was identical to that formed in vivo,
      indicating that the metabolic pathway for the formation of group II adducts did
      not involve 4-hydroxytamoxifen. In conclusion, the results support a model where
      primary metabolites of tamoxifen undergo secondary metabolism to form DNA
      adducts, which are detected in vivo after treatment with tamoxifen or 4
      hydroxytamoxifen.

PMID- 8548776
TI  - Metabolism of docetaxel by human cytochromes P450: interactions with paclitaxel
      and other antineoplastic drugs.
AB  - The metabolism of docetaxel by human liver microsomes was investigated in vitro
      and compared with that of paclitaxel. A main docetaxel metabolite was generated
      by human liver microsomes in the presence of NADPH: retention time in high
      pressure liquid chromatography and its ion fragmentation in mass spectrometry
      were identical to those of the authentic derivative hydroxylated at the butyl
      group of the C13 side chain. Kinetic measurements and chemical and immunological
      inhibitions demonstrated that CYP3A was implicated in the hydroxylation of
      docetaxel: Km (2 microM) and Vm values of docetaxel for human liver microsomes
      were comparable to those calculated for the formation of metabolite p-hydroxy
      phenyl C3' paclitaxel (M4). Docetaxel hydroxylation correlated only with the
      CYP3A content of microsomes and with CYP3A-dependent 6 beta-hydroxylation of
      testosterone and 16-hydroxylation of dehydroepiandrosterone. The formation of
      hydroxydocetaxel was strongly reduced by CYP3A inhibitors such as ketoconazole,
      midazolam, erythromycin, testosterone, orphenadrine, and troleandomycin, whereas
      quinidine (CYP2D6), hexobarbital, tolbutamide, and mephenytoin (CYP2C) had no or
      little effect. The hydroxylation of docetaxel exhibited a highly positive
      correlation with the formation of metabolite M4 of paclitaxel (r = 0.929, P <
      0.0001, n = 12), but not with its 6-hydroxylation (r = 0.48, P > 0.15). Docetaxel
      abolished the hydroxylation of paclitaxel metabolite M4, but was totally inactive
      on its 6 alpha-hydroxylation. Conversely, paclitaxel reduced significantly the
      hydroxylation of docetaxel. We examined in vitro the possible interaction among
      docetaxel, paclitaxel, and drugs which could be associated during chemotherapy.
      Cisplatin, verapamil, doxorubicin, vinblastine, and vincristine at concentrations
      usually recommended did not markedly modify taxoid metabolism. Ranitidine and
      diphenylhydramine had no effect, but 100 microM cimetidine partially inhibited
      the formation of 6 alpha-hydroxypaclitaxel. Pretreatment of patients with
      barbiturates strikingly stimulated docetaxel hydroxylation, whereas no
      acceleration of docetaxel hydroxylation was noticed in a patient receiving
      steroids.

PMID- 8548777
TI  - Identification of the major tamoxifen-deoxyguanosine adduct formed in the liver
      DNA of rats treated with tamoxifen.
AB  - The antiestrogenic drug tamoxifen induces liver tumors in rats by a genotoxic
      mechanism. The key step has been proposed to be the formation of a reactive
      carbocation from the metabolite alpha-hydroxytamoxifen. This compound reacts with
      DNA in vitro to a small extent (1 in 10(5) DNA bases), giving products identical
      to those found in rat liver cells treated with tamoxifen. Now we have prepared
      the more reactive alpha-acetoxytamoxifen, which reacts with DNA in vitro to a
      much greater extent (1 in 50 bases). The products of this reaction were subjected
      to 32P postlabeling and shown by both TLC and reverse-phase liquid chromatography
      to be identical to those isolated from DNA treated with alpha-hydroxytamoxifen
      and to those found in the liver DNA of rat hepatocytes treated with tamoxifen or
      of the livers of rats treated with tamoxifen. The major product was also isolated
      as the nucleoside and characterized by UV, mass, and proton magnetic resonance
      spectroscopy. It is an adduct of tamoxifen and deoxyguanosine in which the alpha
      position of tamoxifen is linked covalently to the exocyclic amino group of
      deoxyguanosine.

PMID- 8548779
TI  - Antisense inhibition of parathyroid hormone-related peptide gene expression
      reduces malignant pituitary tumor progression and metastases in the rat.
AB  - A newly established metastatic rat pituitary tumor (mGH3) possesses a malignant
      phenotype that is invasive and hypervascular compared with the original GH3
      tumors. mGH3 cells exhibit anchorage independence and expression of elevated
      levels of parathyroid hormone-related peptide (PTHrP) in vitro. To clarify the
      role of PTHrP in the development of the malignant phenotype, tumor cells were
      treated with phosphorothioate antisense PTHrP oligonucleotide. Treatment with
      antisense PTHrP resulted in a scattering phenomenon in the colony formation assay
      but did not inhibit cell growth in vitro. Inoculation of mGH3 cells in the
      cerebral ventricle resulted in a rapid growth of tumor cells within 3 weeks and
      dissemination throughout the entire ventricular system. Although treatment with
      sense or mismatched PTHrP oligonucleotide did not influence the subsequent tumor
      growth, the in vivo coinjection and injection of antisense PTHrP 1 week after
      tumor cell implantation into the right lateral ventricle markedly reduced tumor
      size and suppressed metastasis formation. The survival rate of mGH3 tumor
      injected rats was prolonged by antisense PTHrP therapy. Our results demonstrated
      the biological involvement of PTHrP in malignant phenotype in rat pituitary
      tumors, suggesting that antisense PTHrP may provide a novel antimetastatic
      therapy for malignant somatotroph tumors.

PMID- 8548780
TI  - Eradication of interleukin 5-transfected J558L plasmacytomas in mice by hydrogen
      peroxide-generating Stealth liposomes.
AB  - Certain human tumors are extensively infiltrated by eosinophils and contain
      extracellular deposits of eosinophil peroxidase, which uses hydrogen peroxide as
      a substrate to produce highly toxic hypohalous acids. We hypothesized that J558L
      HI, an interleukin 5-transfected murine plasmacytoma that is infiltrated by
      numerous degranulating eosinophils, would be especially sensitive to killing by
      hydrogen peroxide generated by glucose oxidase (beta-D-glucose:oxygen-oxido
      reductase; EC 1.13.4). Here we report that 4 i.v. injections of 0.5 ml of
      hydrogen peroxide-generating, anionic Stealth liposomes containing 50 micrograms
      of glucose oxidase eradicated s.c. implants of 10(6) J558L HI plasmacytoma cells
      in 6 of 13 mice. By contrast, the J558L HI tumors grew rapidly in 13 of 13
      untreated mice and in 10 of 10 mice treated with daily i.v. injections of 50
      micrograms of unencapsulated (free) glucose oxidase (P = 0.002 by log-rank test
      of survival curves constructed using the Kaplan-Meier method). Antisense
      transfected J558L tumors that did not contain eosinophils were not eradicated by
      the peroxide-generating liposomes in any of the 10 mice that were tested.
      Treatment with the liposomes was well tolerated for the first three doses (given
      on days 3, 4, and 5 after tumor inoculation). The fourth dose given on day 10
      produced significant allergic toxicity and was, therefore, omitted in a second
      trial with only minimal reduction in the therapeutic response. We conclude that
      peroxide-generating, anionic Stealth liposomes can eradicate plasmacytomas
      infiltrated by eosinophils in mice. Our results, therefore, suggest that peroxide
      generating compounds may be a useful experimental approach for treating those
      human tumors that are naturally infiltrated by eosinophils but resistant to
      conventional therapies.

PMID- 8548778
TI  - Association of CYP1A1 germ line polymorphisms with mutations of the p53 gene in
      lung cancer.
AB  - We reported an association of smoking-induced lung cancer susceptibility with the
      human cytochrome P450 1A1 (CYP1A1) polymorphisms in our previous studies. To
      investigate a relationship between genetically determined individual
      predispositions and mutations of target genes in the early stage of lung
      carcinogenesis, we examined p53 mutations in relation to germ line polymorphisms
      of the CYP1A1 and GSTM1 genes, using surgical specimens of 148 non-small cell
      lung cancer patients who were smokers. The frequency of p53 mutations among heavy
      smokers was higher than in patients who had never smoked [P < 0.01; odds ratio
      (OR), 3.74; 95% confidence interval (CI), 1.46-9.56]. By single-strand
      conformational polymorphism, aberrant migration bands of p53 gene fragments were
      detected in 56 cases (38%). Smokers with susceptible rare homozygous alleles of
      either the MspI or Ile-Val polymorphism of the CYP1A1 gene have a 4.5-fold (P <
      0.005; OR, 4.48; 95% CI, 1.64-12.26) or 5.5-fold (P < 0.01; OR, 5.52; 95% CI,
      1.55-19.64) higher risk of having a mutation of the p53 gene than those with
      nonsusceptible predominant homozygous alleles of the gene. Non-small cell lung
      cancer patients with a susceptible CYP1A1 genotype were at remarkably high risk
      of having a mutation of the p53 gene when the genotype was combined with a
      deficient genotype, GSTM1(-). However, there was no difference between the types
      of p53 mutation and genotypes of the drug-metabolizing enzymes. These results
      showed that CYP1A1 germ line polymorphisms, which were associated with the
      genetic predisposition for lung cancer, were related to cigarette smoking
      associated p53 mutations.

PMID- 8548781
TI  - Functional expression of human topoisomerase II alpha in yeast: mutations at
      amino acids 450 or 803 of topoisomerase II alpha result in enzymes that can
      confer resistance to anti-topoisomerase II agents.
AB  - DNA topoisomerase II is the target of a variety of important antitumor agents,
      including etoposide, adriamycin, and amsacrine. We have constructed a system for
      analyzing the action of anti-topoisomerase II agents using the yeast
      Saccharomyces cerevisiae and have constructed vectors for expressing human
      topoisomerase II functionally in yeast. We have demonstrated that temperature
      conditional yeast TOP2 mutants can be complemented by expression of wild-type
      human topoisomerase II alpha. Furthermore, expression of human topoisomerase II
      in yeast results in a quantitatively unique pattern of sensitivity to amsacrine.
      We also have constructed mutations in human TOP2 based on previously identified
      mutations from a human cell line selected for resistance to teniposide. Our
      experiments demonstrate that mutation of either arginine 450 or proline 803 of
      human topoisomerase II can result in an enzyme that has altered sensitivity to
      anti-topoisomerase II agents, and that a human enzyme carrying both mutations
      confers a higher level of drug resistance than enzymes carrying either single
      mutation.

PMID- 8548782
TI  - Structural elucidation of the novel type VII group B Streptococcus capsular
      polysaccharide by high resolution NMR spectroscopy.
AB  - The type VII capsular polysaccharide isolated from the newly discovered group B
      Streptococcus (GBS) strain contains D-glucose, D-galactose, N-acetyl-D
      glucosamine and N-acetylneuraminic acid in the molar ratio 2:2:1:1. High
      resolution one- and two-dimensional (1D and 2D) 1H and 13C NMR spectroscopy of
      the native and desialylated polysaccharides showed the type VII GBS capsular
      polysaccharide to contain the following branched hexasaccharide repeating unit:
      [formula: see text] Despite extensive structural similarity with the previously
      described GBS polysaccharides, the type VII polysaccharide showed no cross
      reaction with the heterologous antisera.

PMID- 8548783
TI  - Chemical synthesis of 6'-alpha-maltosyl-maltotriose, a branched oligosaccharide
      representing the branch point of starch.
AB  - Chemical synthesis of the branched pentasaccharide 6'-alpha-maltosyl-maltotriose
      (15) is reported, based on the use of one synthon as a glycosyl acceptor and
      another synthon as a glycosyl donor. The synthon used as glycosyl acceptor was
      phenyl 2,3,6-tri-O-benzyl-1-thio-beta-D-glucopyranoside (7) and was synthesized
      from D-glucose with phenyl 2,3-di-O-acetyl-4,6-O-benzylidene-1-thio-beta-D
      glucopyranoside and phenyl 2,3-di-O-benzyl-4,6-O-benzylidene-1-thio-beta-D
      glucopyranoside as key intermediates. The synthon used as glycosyl donor was O
      (2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl)-(1-->4)-O-(2,3,6-tri-O -benzyl -
      alpha-D-glucopyranosyl)-(1-->6)-O-[(2,3,4,6-tetra-O-benzyl-alpha-D-
      glucopyranosyl)-(1-->4)]-2,3-di-O-benzyl-alpha,beta-D-glucopyranosyl
      trichloroacetimidate (12) and was synthesized from phenyl O-2,3,4,6-tetra-O
      benzyl-alpha-D-glucopyranosyl)-(1-->4)-O-(2,3,6-tri-O- benzyl- alpha-D
      glucopyranosyl)-(1-->6)-O-[(2,3,4,6-tetra-O-acetyl-alpha-D- glucopyranosyl)-(1-
      >4)]-2,3-di-O-acetyl-1-thio-beta-D-glucopyranoside with O-(2,3,4,6-tetra-O-benzyl
      alpha-D-glucopyranosyl)-(1-->4)-O-(2,3,6-tri-O - benzyl-alpha-D-glucopyranosyl)
      (1-->4)]-2,3-di-O-benzyl-D-glucopyranose as an intermediate. Condensation of
      compounds 7 and 12 followed by removal of the phenylthio group and debenzylation
      provided the branched pentasaccharide 15. Alternatively, the branched
      pentasaccharide was produced from amylopectin by consecutive alpha- and beta
      amylase treatments and purified by chromatography. The identity of the products
      obtained by chemical synthesis and enzymatic hydrolysis is documented by 1H and
      13C NMR spectra.

PMID- 8548784
TI  - Conformational analysis of heparin epoxide in aqueous solution. An NMR relaxation
      study.
AB  - 1H and 13C NMR relaxation measurements at various magnetic fields have been used
      to characterize the nature of overall and internal motions in heparin epoxide in
      aqueous solution. A two-dimensional homonuclear NOESY experiment showed a
      considerable number of cross-relaxing protons in the molecule. The inter-proton
      distances calculated from NOE data were compared with those obtained by molecular
      mechanics calculations. Several discrepancies between the experimental and the
      theoretical inter-proton distances as well as the variations in 13C spin-lattice
      relaxation times, measured at two magnetic fields, indicated that the
      polysaccharide tumbles anisotropically in solution. The rates of overall and
      internal motions as well as the order parameters have been calculated using a
      model-free spectral density function. The numerical values indicate that the
      correlation times which characterize overall molecular motion are outside the
      extreme narrowing limit (tau parallel = 8 x 10(-10) s and tau perpendicular = 4.2
      x 10(-8) s) and that internal motion correlation time is on a picosecond
      timescale.

PMID- 8548785
TI  - Hydrolysis of the GlcNAc oxazoline: deamidation and acyl rearrangement.
AB  - The specific deamidation of 2-acetamido-1,3,4,6-tetra-O-acetyl-alpha-D
      glucopyranose is achieved by p-toluenesulfonic acid-promoted hydrolysis of 2
      methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-alpha-D-glucopyrano)-[2,1 -d]-2- oxazoline
      2 to give quantitative formation of the 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy
      alpha-D-glucopyranose p-toluenesulfonate (5d). This two-step procedure provides
      an amino sugar which may be readily acylated to give novel glycoconjugates.
      Alternatively, base-catalyzed O-1-->N-2 acyl rearrangement of the amino tosylate
      5d gives the 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranose 4 as a 9:1
      mixture of alpha and beta anomers. Thus, hydrolysis of GlcNAc oxazoline 2 gives
      the amino-ester 5 as the kinetic product and the amido-alcohol 4 as the
      thermodynamic product.

PMID- 8548786
TI  - Characterization of five type II arabinogalactan-protein fractions from red wine
      of increasing uronic acid content.
AB  - Five arabinogalactan-protein conjugates (AGP) were separated from red wine by two
      successive anion-exchange chromatography steps and further purified to apparent
      homogeneity by affinity and size-exclusion chromatography. Together they
      represent more than 40% of total wine polysaccharides, confirming the abundance
      of AGPs in red wine. The five purified fractions had a common arabinogalactan
      core with characteristics typical of wine type II AGPs, but differed mainly in
      their uronic acid content, as evidenced by differences in the strength of their
      binding to the anion-exchanger. Their uronic acid content and glycosidic linkage
      composition revealed that the three less acidic AGPs contained from 3 to 7%
      glucuronic acid, half in terminal non-reducing positions and half in terminal
      Rhap-(1-->4)-Glc pA-(1-->sequences. The two more acidic AGP-containing fractions
      contained both glucuronic (6.1 and 13.3%, respectively) and galacturonic (1.9 and
      2.3%, respectively) acid in association with 2- and 2,4-linked rhamnose,
      indicating the presence of AG-rhamnogalacturonan fragments.

PMID- 8548787
TI  - Stereoselective preparation of alkyl glycosides of 2-acetamido-2-deoxy-alpha-D
      glucopyranose by nonclassical halide-ion catalysis and synthesis and NMR
      spectroscopy of alpha-D-Gal p-(1-->3)-alpha-D-Glc pNAc-OMe.

PMID- 8548788
TI  - Structural study of a polysaccharide from the seeds of Borassus flabellifer Linn.

PMID- 8548789
TI  - Conformational analysis of heparin epoxide: molecular mechanics computations.
AB  - The conformation of models of the epoxy-derivative of the glycosaminoglycan
      heparin has been studied by molecular mechanics calculations using a MM2-like
      force field extended with parameters for the oxirane ring. Two dimers, two
      trimers and several higher homologs modeling heparin epoxide were investigated,
      assuming the preferred 5H0 ring form of 2,3-anhydro-alpha-L-guluronic acid
      residue. Two-dimensional (phi; psi) maps of dimers showed the location of the
      energetically preferred conformers. Starting from the most stable dimer
      conformers, structures of trimers and other oligomers were derived and optimized,
      with an exhaustive search of the preferred sidechain conformers. The effect of
      solvation on conformation was analyzed using a continuum model of solvent. The
      present calculations indicate a significant flexibility of the heparin epoxide
      chain.

PMID- 8548790
TI  - Synthesis of a pentasaccharide fragment of Polysaccharide II of Mycobacterium
      tuberculosis.
AB  - Stereocontrolled, stepwise synthesis of decyl glycosides of alpha-(1-->2)-linked
      di- to pentaglucosides (1-5) is described; these constitute fragments of
      Polysaccharide II of Mycobacterium tuberculosis. Phenyl 3,4,6-tri-O-acetyl-2-O
      benzyl-1-thio-alpha-D- glucopyranoside (7) was used as the single key
      intermediate, obtained from 1,3,4,6-tetra-O-acetyl-2-O-benzyl-beta-D
      glucopyranose (6) and PhSSiMe3. Halogenolysis of 7 afforded the isolated beta
      bromide (10) and beta chloride (13). Solvolysis of 10 with decanol without heavy
      metal salts gave decyl 3,4,6-tri-O-acetyl-2-O-benzyl-alpha-D-glucopyranoside (14)
      in a highly stereoselective reaction, in high yield. Subsequent, iterative
      hydrogenolytic removal of the O-benzyl group and glycosylation with the beta
      chloride 13 under catalysis by silver salts afforded the protected di- to penta
      saccharide glycosides 16, 19, 21, and 23, which were conventionally deblocked.

PMID- 8548791
TI  - Structural analysis of the carbohydrate moiety of arabinogalactan-proteins from
      stigmas and styles of Nicotiana alata.
AB  - Arabinogalactan-proteins (AGPs) from the female reproductive tissues (stigmas and
      styles) of Nicotiana alata were isolated from the saturated ammonium sulfate
      supernatant of buffer-soluble extracts by precipitation with the beta-glucosyl
      Yariv reagent, followed by gel-filtration chromatography under dissociating
      conditions. The AGPs had characteristics typical of other AGPs: a high proportion
      of carbohydrate (95%) with a high ratio of Gal p to Ara f (2:1), and a low
      protein content (5%) with high levels of alanine, serine, and hydroxyproline. The
      AGPs consisted of a major species which was almost neutral, and a minor species
      which was more negatively charged. Sedimentation equilibrium experiments showed
      that the purified AGPs had a weight-average molecular weight of 143 kD. Linkage
      analysis showed that the AGPs contained a highly branched backbone of 3-, 6-, and
      3,6-linked Gal p residues, bearing terminal Gal p and terminal Ara f residues.
      Analysis by one-dimensional and two-dimensional 1H and 13C NMR spectroscopy
      confirmed the presence of these glycosyl linkage types, and showed a high
      mobility of the terminal Ara f residues consistent with their location on the
      periphery of the molecules. This analysis represents the most complete 1H
      assignment for AGP molecules in solution. No difference in the carbohydrate
      analyses was found between AGPs isolated separately from stigmatic or stylar
      tissue, or between AGPs isolated from stigmas and styles of plants of different
      self-incompatibility genotypes.

PMID- 8548792
TI  - Melatonin madness.

PMID- 8548793
TI  - DNA transposition: from a black box to a color monitor.

PMID- 8548794
TI  - Basic FGF as an inducer of anteroposterior neural pattern.

PMID- 8548795
TI  - Talking through walls: signaling in plant development.

PMID- 8548796
TI  - The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair
      and V(D)J recombination.
AB  - The XR-1 Chinese hamster ovary cell line is impaired in DNA double-strand break
      repair (DSBR) and in ability to support V(D)J recombination of transiently
      introduced substrates. We now show that XR-1 cells support recombination
      activating gene 1- and 2-mediated initiation of V(D)J recombination within a
      chromosomally integrated substrate, but are highly impaired in ability to
      complete the process by forming coding and recognition sequence joins. On this
      basis, we isolated a human cDNA sequence, termed XRCC4, whose expression confers
      normal V(D)J recombination ability and significant restoration of DSBR activity
      to XR-1, clearly demonstrating that this gene product is involved in both
      processes. The XRCC4 gene maps to the previously identified locus on human
      chromosome 5, is deleted in XR-1 cells, and encodes a ubiquitously expressed
      product unrelated to any described protein.

PMID- 8548797
TI  - Virus induction of human IFN beta gene expression requires the assembly of an
      enhanceosome.
AB  - We present evidence that transcriptional activation of the human interferon-beta
      (IFN beta) gene requires the assembly of a higher order transcription enhancer
      complex (enhanceosome). This multicomponent complex includes at least three
      distinct transcription factors and the high mobility group protein HMG I(Y). Both
      the in vitro assembly and in vivo transcriptional activity of this complex
      require a precise helical relationship between individual transcription factor
      binding sites. In addition, HMG I(Y), which binds specifically to three sites
      within the enhancer, promotes cooperative binding of transcriptional factors in
      vitro and is required for transcriptional synergy between these factors in vivo.
      Thus, HMG I(Y) plays an essential role in the assembly and function of the IFN
      beta gene enhanceosome.

PMID- 8548798
TI  - Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription
      factors and the architectural protein HMG I(Y).
AB  - In this paper, we investigate DNA bending induced by proteins required for virus
      induction of the human interferon-beta (IFN beta) gene. We show that NF-kappa B
      DNA complexes that are functionally distinct in the context of the IFN beta
      enhancer are also conformationally distinct and that two sites in the enhancer
      contain in-phase bends that are counteracted or reversed by the binding of NF
      kappa B, ATF-2/c-Jun, and HMG I(Y). Strikingly, this modulation of intrinsic
      enhancer architecture results in an orientation that favors predicted protein
      protein interactions in a functional nucleoprotein complex, the enhanceosome.
      Furthermore, the subtle modulation of DNA structure by HMG I(Y) in this process
      distinguishes it from other architectural factors.

PMID- 8548799
TI  - The 3' enhancer region determines the B/T specificity and pro-B/pre-B specificity
      of immunoglobulin V kappa-J kappa joining.
AB  - Using transgenic substrates, we found that the immunoglobulin kappa gene 3'
      enhancer (E3') acts as a negative regulator in V kappa-J kappa joining. Although
      the E3' was originally identified as a transcriptional enhancer, it acts in a
      suppressive manner for recombinational regulation. Base substitution analysis has
      shown that the PU.1-binding site within the E3' regulates the B/T specificity of
      V kappa-J kappa joining. In a substrate with a mutated PU.1-binding site (GAGGAA
      to TCTTCG), V kappa-J kappa joining occurred not only in B cells, but also in T
      cells. The E3' region is also responsible for determining the pro-B/pre-B
      specificity of V kappa-J kappa joining. When the E3' region was deleted, kappa
      gene rearrangement actively occurred at the early pro-B stage of B cell
      development: nongermline (N) nucleotides were common at recombination junctions.

PMID- 8548800
TI  - Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH
      proteins.
AB  - Members of the myocyte enhancer factor-2 (MEF2) family of MADS domain
      transcription factors cannot induce myogenesis in transfected fibroblasts, but
      when coexpressed with the myogenic basic-helix-loop-helix (bHLH) proteins MyoD or
      myogenin they dramatically increase the extent of myogenic conversion above that
      seen with either myogenic bHLH factor alone. This cooperativity required direct
      interactions between the DNA-binding domains of MEF2 and the myogenic bHLH
      factors, but only one of the factors needed a transactivation domain, and only
      one of the factors needed to be bound to DNA. These interactions allow either
      factor to activate transcription through the other's binding site and reveal a
      novel mechanism for indirect activation of gene expression via protein-protein
      interactions between the DNA-binding domains of heterologous classes of
      transcription factors.

PMID- 8548801
TI  - SARs are cis DNA elements of chromosome dynamics: synthesis of a SAR repressor
      protein.
AB  - SARs are candidate DNA elements for defining the bases of chromatin loops and
      possibly for serving as cis elements of chromosome dynamics. SARs contain
      numerous A tracts, whose altered DNA structure is recognized by cooperatively
      interacting proteins such as topoisomerase II. We constructed multi-AT hook
      (MATH) proteins and demonstrate that they specifically bind the clustered A
      tracts of SARs in chromatin and chromosomes. They are also potent inhibitors of
      chromosome assembly in mitotic Xenopus extracts, demonstrating the importance of
      SARs in this process. Titration of SARs with MATH20 (20 hooks) blocks shape
      determination of chromatids but not chromatin condensation per se. SARs are also
      required for shape maintenance of chromosomes. If MATH20 is added after formation
      of chromatids, they collapse and are reshaped by an active, mitotic process into
      spherical chromatid balls.

PMID- 8548802
TI  - Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of
      an S phase checkpoint.
AB  - Commitment of mammalian cells to enter S phase enables the transcription factor
      E2F-1 to activate certain genes whose products mediate cell cycle advance. In S
      phase, E2F-1 forms stable complexes with cyclin A-kinase, which in turn
      eliminates E2F-1DNA binding function. Here, we show that suppression of E2F-1 DNA
      binding activity by cyclin A-kinase is linked to orderly S phase progression.
      Disruption of this linkage resulted in S phase delay/arrest followed by regrowth
      or apoptosis, depending upon whether the DNA-bound E2F-1 could transactivate.
      Hence, the unscheduled presence of E2F-1 on specific DNA sequences during S phase
      can activate a specific S phase checkpoint, thereby linking transcription, DNA
      replication, and cell cycle control.

PMID- 8548803
TI  - Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin
      related motor essential for bipolar spindle formation in vivo.
AB  - We have isolated a human homolog of Xenopus Eg5, a kinesin-related motor protein
      implicated in the assembly and dynamics of the mitotic spindle. We report that
      microinjection of antibodies against human Eg5 (HsEg5) blocks centrosome
      migration and causes HeLa cells to arrest in mitosis with monoastral microtubule
      arrays. Furthermore, an evolutionarily conserved cdc2 phosphorylation site (Thr
      927) in HsEg5 is phosphorylated specifically during mitosis in HeLa cells and by
      p34cdc2/cyclin B in vitro. Mutation of Thr-927 to nonphosphorylatable residues
      prevents HsEg5 from binding to centrosomes, indicating that phosphorylation
      controls the association of this motor with the spindle apparatus. These results
      indicate that HsEg5 is required for establishing a bipolar spindle and that
      p34cdc2 protein kinase directly regulates its localization.

PMID- 8548804
TI  - SecA membrane cycling at SecYEG is driven by distinct ATP binding and hydrolysis
      events and is regulated by SecD and SecF.
AB  - The SecA subunit of E. coli preprotein translocase promotes protein secretion
      during cycles of membrane insertion and deinsertion at SecYEG. This process is
      regulated both by nucleotide binding and hydrolysis and by the SecD and SecF
      proteins. In the presence of associated preprotein, the energy of ATP binding at
      nucleotide-binding domain 1 (NBD1) drives membrane insertion of a 30 kDa domain
      of SecA, while deinsertion of SecA requires the hydrolysis of this ATP. SecD and
      SecF stabilize the inserted state of SecA. ATP binding at NBD2, though needed for
      preprotein translocation, is not needed for SecA insertion or deinsertion.

PMID- 8548805
TI  - COPI- and COPII-coated vesicles bud directly from the endoplasmic reticulum in
      yeast.
AB  - The cytosolic yeast proteins Sec13p-Sec31p, Sec23p-Sec24p, and the small GTP
      binding protein Sar1p generate protein transport vesicles by forming the membrane
      coat termed COPII. We demonstrate by thin section and immunoelectron microscopy
      that purified COPII components form transport vesicles directly from the outer
      membrane of isolated yeast nuclei. Another set of yeast cytosolic proteins,
      coatomer and Arf1p (COPI), also form coated buds and vesicles from the nuclear
      envelope. Formation of COPI-coated, but not COPII-coated, buds and vesicles on
      the nuclear envelope is inhibited by the fungal metabolite brefeldin A. The two
      vesicle populations are distinct. However, both vesicle types are devoid of
      endoplasmic reticulum (ER) resident proteins, and each contains targeting
      proteins necessary for docking at the Golgi complex. Our data suggest that COPI
      and COPII mediate separate vesicular transport pathways from the ER.

PMID- 8548806
TI  - Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic.
AB  - Mice unable to synthesize dopamine (DA) specifically in dopaminergic neurons were
      created by inactivating the tyrosine hydroxylase (TH) gene then by restoring TH
      function in noradrenergic cells. These DA-deficient (DA-/-) mice were born at
      expected frequency but became hypoactive and stopped feeding a few weeks after
      birth. Midbrain dopaminergic neurons, their projections, and most characteristics
      of their target neurons in the striatum appeared normal. Within a few minutes of
      being injected with L-dihdroxyphenylalanine (L-DOPA), the product of TH, the DA-/
      mice became more active and consumed more food than control mice. With continued
      administration of L-DOPA, nearly normal growth was achieved. These studies
      indicate that DA is essential for movement and feeding, but is not required for
      the development of neural circuits that control these behaviors.

PMID- 8548807
TI  - A genetic test of the effects of mutations in PKA on mossy fiber LTP and its
      relation to spatial and contextual learning.
AB  - Using a genetic approach, we assessed the effects of mutations in protein kinase
      A (PKA) on long-term potentiation (LTP) in the mossy fiber pathway and its
      relationship to spatial and contextual learning. Ablation by gene targeting of
      the C beta 1 or the RI beta isoform of PKA produces a selective defect in mossy
      fiber LTP, providing genetic evidence for the role of these isoforms in the mossy
      fiber pathway. Despite the elimination of mossy fiber LTP, the behavioral
      responses to novelty, spatial learning, and conditioning to context are
      unaffected. Thus, contrary to current theories about hippocampal function, mossy
      fiber LTP does not appear to be required for spatial or contextual learning. In
      the absence of mossy fiber LTP, adequate spatial and contextual information might
      reach the CA1 region via other pathways from the entorhinal cortex.

PMID- 8548808
TI  - Impaired synapse elimination during cerebellar development in PKC gamma mutant
      mice.
AB  - PKC gamma is highly expressed in Purkinje cells (PCs) but not in other types of
      neurons in the cerebellum. The expression of PKC gamma changes markedly during
      cerebellar development, being very low at birth and reaching a peak around the
      third postnatal week. This temporal pattern of PKC gamma expression coincides
      with the developmental transition from multiple to single climbing fiber
      innervation onto each PC. In adult mutant mice deficient in PKC gamma, we found
      that 41% of PCs are still innervated by multiple climbing fibers, while other
      aspects of the cerebellum including the morphology and excitatory synaptic
      transmission of PCs appear normal. Thus, elimination of multiple climbing fiber
      innervation appears to be specifically impaired in the mutant cerebellum. We
      suggest that the developmental role of PKC gamma may be to act as a downstream
      element in the signal cascade necessary for the elimination of surplus climbing
      fiber synapses.

PMID- 8548809
TI  - Impaired motor coordination correlates with persistent multiple climbing fiber
      innervation in PKC gamma mutant mice.
AB  - It is generally believed that a smooth execution of a compound movement, or motor
      coordination, requires learning of component movements as well as experience
      based refinement of the motor program as a whole. PKC gamma mutant mice display
      impaired motor coordination but intact eyeblink conditioning, a form of component
      movement learning. Cerebellar long-term depression, a putative cellular mechanism
      for component motor learning, is also unimpaired. Thus, PKC gamma mutant mice are
      defective in refinement of the motor program. In the accompanying paper, we
      demonstrate that innervation of multiple climbing fibers onto Purkinje cells
      persists in adulthood in these mutant mice. We propose that this defective
      elimination of surplus climbing fibers underlies motor discoordination.

PMID- 8548810
TI  - The TNFR2-TRAF signaling complex contains two novel proteins related to
      baculoviral inhibitor of apoptosis proteins.
AB  - The 75 kDa tumor necrosis factor receptor (TNFR2) transduces extracellular
      signals via receptor-associated cytoplasmic proteins. Two of these signal
      transducers, TRAF1 and TRAF2, were isolated and characterized previously. We
      report here the biochemical purification and subsequent molecular cloning of two
      novel TNFR2-associated proteins, designated c-IAP1 and c-IAP2, that are closely
      related mammalian members of the inhibitor of apoptosis protein (IAP) family
      originally identified in baculoviruses. The viral and cellular IAPs contain N
      terminal baculovirus IAP repeat (BIR) motifs and a C-terminal RING finger. The c
      IAPs do not directly contact TNFR2, but rather associate with TRAF1 and TRAF2
      through their N-terminal BIR motif-comprising domain. The recruitment of c-IAP1
      or c-IAP2 to the TNFR2 signaling complex requires a TRAF2-TRAF1 heterocomplex.

PMID- 8548811
TI  - Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to
      block cell death.
AB  - Apoptotic cell death is a mechanism by which organisms eliminate superfluous or
      harmful cells. Expression of the cell death regulatory protein REAPER (RPR) in
      the developing Drosophila eye results in a small eye owing to excess cell death.
      We show that mutations in thread (th) are dominant enhancers of RPR-induced cell
      death and that th encodes a protein homologous to baculovirus inhibitors of
      apoptosis (IAPs), which we call Drosophila IAP1 (DIAP1). Overexpression of DIAP1
      or a related protein, DIAP2, in the eye suppresses normally occurring cell death
      as well as death due to overexpression of rpr or head involution defective. IAP
      death-preventing activity localizes to the N-terminal baculovirus IAP repeats, a
      motif found in both viral and cellular proteins associated with death prevention.

PMID- 8548812
TI  - Identification and expression cloning of a leptin receptor, OB-R.
AB  - The ob gene product, leptin, is an important circulating signal for the
      regulation of body weight. To identify high affinity leptin-binding sites, we
      generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as
      [125I]leptin. After a binding survey of cell lines and tissues, we identified
      leptin-binding sites in the mouse choroid plexus. A cDNA expression library was
      prepared from mouse choroid plexus and screened with a leptin-AP fusion protein
      to identify a leptin receptor (OB-R). OB-R is a single membrane-spanning receptor
      most related to the gp130 signal-transducing component of the IL-6 receptor, the
      G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not only in choroid
      plexus, but also in several other tissues, including hypothalamus. Genetic
      mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of
      mouse chromosome 4 that contains the db locus.

PMID- 8548813
TI  - Worm sperm and advances in cell locomotion.

PMID- 8548814
TI  - Reconstitution in vitro of the motile apparatus from the amoeboid sperm of
      Ascaris shows that filament assembly and bundling move membranes.
AB  - We have developed an in vitro motility system from Ascaris sperm, unique amoeboid
      cells that use filament arrays composed of major sperm protein (MSP) instead of
      an actin-based apparatus for locomotion. Addition of ATP to sperm extracts
      induces formation of fibers approximately 2 microns in diameter. These fibers
      display the key features of the MSP cytoskeleton in vivo. Each fiber consists of
      a meshwork of MSP filaments and has at one end a vesicle derived from the plasma
      membrane at the leading edge of the cell. Fiber growth is due to filament
      assembly at the vesicle; thus, fiber elongation results in vesicle translocation.
      This in vitro system demonstrates directly that localized polymerization and
      bundling of filaments can move membranes and provides a powerful assay for
      evaluating the molecular mechanism of amoeboid cell motility.

PMID- 8548815
TI  - EGL-10 regulates G protein signaling in the C. elegans nervous system and shares
      a conserved domain with many mammalian proteins.
AB  - The frequencies of certain periodic behaviors of the nematode C. elegans are
      regulated in a dose-dependent manner by the activity of the gene egl-10. These
      behaviors are modulated oppositely by the activity of the G protein alpha subunit
      gene goa-1, suggesting that egl-10 may regulate a G protein signaling pathway in
      a dose-dependent fashion. egl-10 encodes a protein similar to Sst2p, a negative
      regulator of G protein signaling in yeast. EGL-10 protein is localized in neural
      processes, where it may function in neurotransmitter signaling. Two previously
      known and 13 newly identified mammalian genes have similarity to egl-10 and SST2,
      and we propose that members of this family regulate many G protein signaling
      pathways.

PMID- 8548816
TI  - Roles for FGF8 in the induction, initiation, and maintenance of chick limb
      development.
AB  - We provide evidence that FGF8 serves as an endogenous inducer of chick limb
      formation and that its expression in the intermediate mesoderm at the appropriate
      time and place to trigger forelimb development is directly linked to the
      mechanism of embryonic kidney differentiation. One function of the limb inducer
      is to initiate Fgf8 gene expression in the ectoderm overlying the prospective
      limb-forming territories. FGF8 secreted by the ectoderm then appears to initiate
      limb bud formation by promoting outgrowth of and Sonic hedgehog expression in the
      underlying lateral plate mesoderm. FGF8 also maintains mesoderm outgrowth and
      Sonic hedgehog expression in the established limb bud. Our data thus point to
      FGF8 as a key regulator of limb development that not only induces and initiates
      the formation of a limb bud, but also sustains its subsequent development.

PMID- 8548817
TI  - Membrane dynamics in endocytosis.

PMID- 8548818
TI  - A molecular switch in a replication machine defined by an internal competition
      for protein rings.
AB  - Replication machines use ring-shaped clamps that encircle DNA to tether the
      polymerase to the chromosome. The clamp is assembled on DNA by a clamp loader.
      This report shows that the polymerase and clamp loader coordinate their actions
      with the clamp by competing for it through overlapping binding sites. The
      competition is modulated by DNA. In the absence of DNA, the clamp associates with
      the clamp loader. But after the clamp is placed on DNA, the polymerase develops a
      tight grip on the clamp and out-competes the clamp loader. After replication of
      the template, the polymerase looses affinity for the clamp. Now the clamp loader
      regains access to the clamp and removes it from DNA thus recycling it for future
      use.

PMID- 8548819
TI  - E. coli SSB activates N4 virion RNA polymerase promoters by stabilizing a DNA
      hairpin required for promoter recognition.
AB  - Bacteriophage N4 virion RNA polymerase transcription of double-stranded promoter
      containing DNAs requires supercoiled template and E. coli single-stranded DNA
      binding protein (EcoSSB); other single-stranded DNA-binding proteins cannot
      substitute. The DNA determinants of virion RNA polymerase binding at the promoter
      comprise a small template-strand hairpin. The requirement for EcoSSB is
      surprising, since single-stranded DNA-binding proteins destabilize hairpin
      structures. DNA footprinting of EcoSSB on wild-type and mutant promoters
      indicates that EcoSSB stabilizes the template-strand hairpin owing to the hairpin
      loop sequences. Other single-stranded DNA-binding proteins destabilize the
      promoter hairpin, explaining the specificity of EcoSSB activation. We conclude
      that EcoSSB activates transcription by providing the appropriate DNA structure
      for polymerase binding. The existence of small hairpins stable to single-stranded
      protein binding suggests a novel mechanism that provides structural determinants
      for specific recognition in single-stranded DNA transactions by an otherwise
      nonspecific DNA-binding protein.

PMID- 8548820
TI  - 2.0 A crystal structure of a four-domain segment of human fibronectin
      encompassing the RGD loop and synergy region.
AB  - We have determined the 2.0 A crystal structure of a fragment of human fibronectin
      encompassing the seventh through the RGD-containing tenth type III repeats (FN7
      10). The structure reveals an extended rod-like molecule with a long axis of
      approximately 140 A and highly variable relationships between adjacent domains.
      An unusually small rotation between domains 9 and 10 creates a distinctive
      binding site, in which the RGD loop from domain 10 and the "synergy" region from
      domain 9 are on the same face of FN7-10 and thus easily accessible to a single
      integrin molecule. The cell-binding RGD loop is well-ordered in this structure
      and extends approximately 10 A away from the FN7-10 core.

PMID- 8548821
TI  - Mg2+ as an extracellular signal: environmental regulation of Salmonella
      virulence.
AB  - Ions are not traditionally thought to act as first messengers in signal
      transduction cascades. However, while searching for genes regulated by the
      PhoP/PhoQ virulence regulatory system of Salmonella typhimurium, we recovered two
      loci whose expression is controlled by the concentration of Mg2+. To determine
      whether Mg2+ is the signal modulating the whole PhoP/PhoQ system, we evaluated
      the gene expression pattern of six PhoP-activated genes. Growth in physiological
      concentrations of divalent cations repressed transcription of PhoP-activated
      genes and rendered wild-type Salmonella phenotypically PhoP-. Mg2+ changed the
      conformation of the periplasmic domain of PhoQ, identifying this protein as a
      Mg2+ sensor. A mutation in the sensing domain of PhoQ altered the set point for
      Mg2+ and rendered Salmonella avirulent.

PMID- 8548822
TI  - The human p62 cDNA encodes Sam68 and not the RasGAP-associated p62 protein.

PMID- 8548823
TI  - Separation of sister chromatids in mitosis requires the Drosophila pimples
      product, a protein degraded after the metaphase/anaphase transition.
AB  - Mutations in the Drosophila genes pimples and three rows result in a defect of
      sister chromatid separation during mitosis. As a consequence, cytokinesis is also
      defective. However, cell cycle progression including the mitotic degradation of
      cyclins A and B is not blocked by the failure of sister chromatid separation, and
      as a result, metaphase chromosomes with twice the normal number of chromosome
      arms still connected in the centromeric region are observed in the following
      mitosis, pimples encodes a novel protein that is rapidly degraded in mitosis. Our
      observations suggest that Pimples and Three rows act during mitosis to release
      the cohesion between sister centromeres.

PMID- 8548824
TI  - XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics
      during mitotic spindle assembly.
AB  - We isolated a cDNA clone encoding a kinesin-related protein, which we named
      XKCM1. Antibodies to XKCM1 stain mitotic centromeres and spindle poles.
      Immunodepletion and antibody addition experiments in an in vitro spindle assembly
      assay show that XKCM1 is required for both establishment and maintenance of
      mitotic spindles. The structures that form in the absence of XKCM1 contain
      abnormally long microtubules. This long microtubule defect can be rescued by the
      addition of purified XKCM1 protein. Analysis of microtubule dynamics in a
      clarified mitotic extract reveals that loss of XKCM1 function causes a 4-fold
      suppression in the catastrophe frequency. XKCM1 thus exhibits a novel activity
      for a kinesin-related protein by promoting microtubule depolymerization during
      mitotic spindle assembly.

PMID- 8548825
TI  - Xklp2, a novel Xenopus centrosomal kinesin-like protein required for centrosome
      separation during mitosis.
AB  - We describe a novel Xenopus plus end-directed kinesin-like protein (KLP), Xklp2,
      localized on centrosomes throughout the cell cycle and on spindle pole
      microtubules during metaphase. Using mitotic spindles assembled in Xenopus egg
      extracts and different recombinant GST-Xklp2 mutants, we show that this motor is
      targeted to spindle poles through its C-terminal domain. Xklp2-truncated
      polypeptides lacking the motor domain block centrosome separation and disrupt
      preassembled metaphase spindles. Antibodies directed against the tail of Xklp2
      have a similar effect. These results show that Xklp2 protein is required for
      centrosome separation and maintenance of spindle bipolarity. This study is an
      example of the application of the dominant negative mutant effect on spindle
      assembly in Xenopus egg extracts, demonstrating the usefulness of this approach
      in probing the function of proteins in this system.

PMID- 8548826
TI  - DNA polymerase III: running rings around the fork.

PMID- 8548827
TI  - Cytokinesis in the Arabidopsis embryo involves the syntaxin-related KNOLLE gene
      product.
AB  - The embryo of the flowering plant Arabidopsis develops by a regular pattern of
      cell divisions and cell shape changes. Mutations in the KNOLLE (KN) gene affect
      the rate and plane of cell divisions as well as cell morphology, resulting in
      mutant seedlings with a disturbed radial organization of tissue layers. At the
      cellular level, mutant embryos are characterized by incomplete cross walls and
      enlarged cells with polyploid nuclei. The KN gene was isolated by positional
      cloning. The predicted KN protein has similarity to syntaxins, a protein family
      involved in vesicular trafficking. During embryogenesis, KN transcripts are
      detected in patches of single cells or small cell groups. Our results suggest a
      function for KN in cytokinesis.

PMID- 8548828
TI  - Cdk2 kinase is required for entry into mitosis as a positive regulator of Cdc2
      cyclin B kinase activity.
AB  - In higher eukaryotes, Cdk2 kinase plays an essential role in regulating the G1-S
      transition. Here, we use cycling Xenopus egg extracts to examine the requirement
      of Cdk2 kinase on progression into mitosis. Interestingly, when Cdk2 kinase
      activity is inhibited by the Cdk-specific inhibitor, p21Cip1, a block to mitosis
      occurs, and inactive Cdc2-cyclin B accumulates. This block occurs in the absence
      of nuclei and is not due to direct inhibition of Cdc2 by Cip. Importantly, this
      block to mitosis is reversible by restoring Cdk2-cyclin E kinase activity to a
      Cip-treated cycling extract. Moreover, immunodepletion of Cdk2 from interphase
      extracts prevents activation of Cdc2 upon the addition of exogenous cyclin B.
      Thus, our data show that Cdk2 kinase is a positive regulator of Cdc2-cyclin B
      complexes and establish a link between Cdk2 kinase and cell cycle progression
      into mitosis.

PMID- 8548829
TI  - Cell cycle control by an essential bacterial two-component signal transduction
      protein.
AB  - Dividing cells must coordinate cell cycle events to ensure genetic stability.
      Here we identify an essential two-component signal transduction protein that
      controls multiple events in the Caulobacter cell cycle, including cell division,
      stalk synthesis, and cell cycle-specific transcription. This protein, CtrA, is
      homologous to response regulator transcription factors and controls transcription
      from a group of cell cycle-regulated promoters critical for DNA replication, DNA
      methylation, and flagellar biogenesis. CtrA activity in the cell cycle is
      controlled both transcriptionally and by phosphorylation. As purified CtrA binds
      an essential DNA sequence motif found within its target promoters, we propose
      that CtrA acts in a phosphorelay signal transduction system to control bacterial
      cell cycle events directly at the transcriptional level.

PMID- 8548830
TI  - Retrohoming: cDNA-mediated mobility of group II introns requires a catalytic RNA.

PMID- 8548831
TI  - Visualizing the spatial relationships between defined DNA sequences and the axial
      region of extracted metaphase chromosomes.
AB  - Using fluorescence in situ hybridization to extracted metaphase chromosomes, we
      present visual evidence that specific human DNA sequences occupy distinctive
      positions with respect to the axial region of chromosomes and that the DNA is
      organized into loops emanating from this region. In a stretch of unique DNA on
      chromosome 11, large loops of DNA can be traced and one specific region
      associated with the axial region of the chromosome. Within rDNA, nontranscribed
      spacer sequences are more closely apposed to the chromosome axis than are rRNA
      genes. Heterochromatic and euchromatic DNAs appear to be organized into loops of
      similar size. We could not detect loops at centromeres; most alphoid DNA appears
      to remain close to the axial region.

PMID- 8548832
TI  - IL-2-resistant hyporesponsiveness induced by CD4 mAbs in OKT3-activated human T
      cells is reversed by CD45RA triggering.
AB  - CD4 monoclonal antibodies (mAbs) are potent immunosuppressive agents which have
      been shown to induce in vivo tolerance to antigens and alloantigens and are
      presently evaluated in humans in the treatment of autoimmune diseases. In
      previous studies, we observed that clinical improvement of CD4 mAb-treated
      psoriasis patients was achieved without depletion of CD4+ lymphocytes and at
      nonsaturating CD4 mAb concentrations, suggesting a functional blockade of CD4+
      lymphocyte responses. In this study, we demonstrate that priming of normal human
      CD4+ T cells by immobilized OKT3 (iOKT3) in the presence of CD4 mAbs in soluble
      phase induces a hyporesponsiveness following subsequent restimulation by iOKT3 in
      the absence of CD4 mAbs. This hyporesponsiveness was not associated with
      increased cell death during priming or restimulation cultures and could be
      reversed by the combination of phorbol ester + ionomycin, demonstrating a
      functional blockade of viable cells by CD4 mAbs. Following iOKT3 restimulation,
      hyporesponsive cells showed a lack of blast transformation and CD25 expression
      and were not able to respond to IL-2 since addition of high doses of exogenous IL
      2 +/- CD28 mAbs did not reverse the hyporesponsiveness. However, costimulation
      with CD45RA mAb completely reversed the hyporesponsiveness, suggesting that CD45
      controlled the CD4-mediated hyporesponsiveness.

PMID- 8548833
TI  - Human intestinal intraepithelial lymphocytes bind to mucosal mesenchymal cells
      through VLA4 and CD11A.
AB  - Human intestinal intraepithelial lymphocytes (IEL), predominantly CD8+ T
      lymphocytes, are uniquely situated at the basolateral surfaces of epithelial
      cells in contact with the myofibroblasts that comprise the basement membrane.
      Since mesenchymal cells may anchor IEL in this location and may also serve as
      antigen-presenting cells, the mechanism of binding to IEL was investigated.
      Lymphocytes were radiolabeled with [51Cr] sodium chromate, cocultured with
      mesenchymal cell monolayers, and the nonadherent lymphocytes removed by washes.
      Those adherent to the monolayers were counted by measuring the amount of
      radiolabel retained in the well. A large fraction of IL-2-activated IEL bound to
      KD (lip fibroblast), HISM (jejunal smooth muscle), and JF (jejunal fibroblast)
      cell lines after a 2-hr incubation: 33 +/- 11, 37 +/-14, and 48 +/- 15%,
      respectively. When monoclonal antibodies directed at the alpha chains of the very
      late activation antigens (CD49) were added alone or combined with anti CD11a to
      assays measuring IEL binding to KD or JF monolayers, the greatest inhibition (33
      to 38%) occurred with anti-alpha 4 combined with anti-CD11a. The majority of IEL
      expressed alpha 1 and alpha 4 before and after a 3-day culture with IL-2, with no
      change in surface density. VCAM-1, a binding partner to alpha 4, was not
      expressed on KD or JF cells, and anti-VCAM antibody had no effect on binding. In
      summary, alpha 4 and CD11a on IEL mediate binding to mesenchymal cells.

PMID- 8548834
TI  - Antiviral immune responses of mice lacking MHC class II or its associated
      invariant chain.
AB  - Induction of T-helper cells and T-B cell interaction have been considered to
      critically depend upon recognition of major histocompatibility complex (MHC)
      class II molecules by the T cell receptor. Mice lacking either MHC class II
      molecules (class II(0/0) mice) or its associated invariant chain (Ii0/0 mice)
      provide new opportunities to test this premise. Immune responses to some protein
      antigens have been studied in these mice; little is known about their ability to
      withstand viral infections. We therefore tested CD8+ effector T cells and CD4+ T
      cell-dependent B cell function during different viral infections. The vesicular
      stomatitis virus (VSV)-specific primary cytotoxic T cell response which is
      largely T-helper-dependent was diminished in Ii(0/0) and absent in class II(0/0)
      mice. The usually less T-helper-dependent cytotoxic vaccinia or lymphocytic
      choriomeningitis virus (LCMV)-specific CD8+ T cell responses were reduced up to
      ninefold in class II(0/0) and up to threefold in Ii(0/0) mice. In class II(0/0)
      mice, the T-helper-independent neutralizing IgM response against the glycoprotein
      of VSV was within normal ranges but, in contrast to previous results on CD4(0/0)
      mice, the T-helper-dependent IgG response was absent. Ii(0/0) mice exhibited a
      normal neutralizing IgM response; in contrast to class II(0/0) mice, they mounted
      a significant, though reduced specific IgG response. Similar results were
      obtained for antibody responses against the nucleoprotein of VSV. Although the T
      helper-cell response upon infection with VSV seemed diminished only a little in
      Ii(0/0) mice, presentation of VSV-G to a class II-restricted specific hybridoma
      was greater than 300-fold reduced in the absence of Ii. This suggests that local
      protein concentrations reached during viral infection in the host are high enough
      to override the Ii deficiency of antigen-presenting cells in vivo.

PMID- 8548835
TI  - Soluble FcR block suppressor T cell activity at low concentration in vitro
      allowing isotype-specific antibody production.
AB  - IgA and IgG binding factors (BF) can be found in the supernatant (Th sup) of
      cultures containing macrophages and CD4+ T cells stimulated with particulate
      antigens such as SRBC. Previous work indicated that these IgBF, when mixed with
      normal serum immunoglobulin, could block the activity of suppressor T cells (Ts)
      and allow IgA and IgG PFC responses in vitro. We present serologic and functional
      evidence that IgABF and IgGBF in Th sup are soluble Fc alpha R and Fc gamma RII
      (or III), respectively. Th sup adsorbed on affinity columns containing anti-Fc
      gamma RII/III mAB or murine IgG failed to augment IgG PFC responses. Material
      eluted from either the IgG or anti-Fc gamma RII/III columns could be added back,
      interchangeably, to the adsorbed Th sup and restore IgG PFC. Recombinant murine
      Fc gamma RII(rFc gamma RII), added to the same adsorbed Th sup at 0.01 to 0.5
      ng/ml, resulted in a similar augmentation of IgG PFC. Interestingly, much higher
      concentrations of rFc gamma RII (10-100 ng/mL) could not augment IgG PFC
      responses. Protein dot blots showed that Th sup and the eluted material from
      murine IgG columns contained structures reactive with the Fc gamma RII/III mAb.
      Similar studies using purified Fc alpha R revealed that IgABF eluted from IgA or
      anti-Fc alpha R revealed that IgABF eluted from IgA or anti-Fc alpha R columns
      was in fact Fc alpha R. Cross-adsorption studies indicated clearly that the IgGBF
      (Fc gamma RII/III) and the IgABF (Fc alpha R) were separate molecules produced in
      the same Th sup and that each regulated their respective Ig isotype
      independently. Thus, cultures of splenic macrophage and CD4+ T cells, in the
      presence of particulate antigens such as SRBC, generate both Fc gamma RII/III and
      Fc alpha R. This soluble FcR in combination with serum Ig act to block isotype
      specific Ts cells at low concentration in vitro.

PMID- 8548836
TI  - A progesterone-induced protein increases the synthesis of asymmetric antibodies.
AB  - The immunological effects of progesterone are mediated by a 34-kDa protein named
      the progesterone-induced blocking factor (PIBF). PIBF induces increased
      production of Th2-type cytokines; thus, it might stimulate antibody synthesis by
      B cells. There is a population of antibodies which, owing to the presence of a
      mannose-rich oligosaccharide residue on one of the Fab arms of the molecule,
      possess an asymmetric structure. Due to the asymmetric structure these molecules
      have no effector functions; however, they might act as blocking antibodies. This
      study was aimed at investigating the effect of progesterone-dependent
      immunomodulation on antibody production by B cells, with special emphasis on the
      synthesis of asymmetric nonprecipitating antibodies. The ratio of asymmetric IgG
      was significantly higher in supernatants of hybridoma cells cultured in the
      presence of PIBF than in those cultured in the absence of PIBF. Lymphocytes from
      healthy pregnant women produce significantly more PIBF than those of women with
      pathological pregnancies. The present studies revealed a positive relationship
      between asymmetric antibody content of the sera and PIBF expression on
      lymphocytes. Blocking of progesterone receptors by RU 486 or neutralizing
      endogenous PIBF activity by specific antibody significantly reduced the
      production of asymmetric antibodies in pregnant mice. Effector function of
      conventional and asymmetric antibodies was compared in a TNF alpha neutralization
      assay. Purified asymmetric anti-TNF alpha antibodies did not neutralize the
      cytotoxic effect of TNF alpha on L929 murine fibroblast target cells, whereas
      conventional anti-TNF alpha antibodies in the same concentration significantly (P
      < 0.001) reduced cytotoxicity. Our data suggest that PIBF induces increased
      production of asymmetric antibodies. These antibodies fail to exhibit effector
      functions and by blocking fetally derived antigens might contribute to protection
      of the fetus.

PMID- 8548837
TI  - Correlation between the concentration of serum anti-topoisomerase I
      autoantibodies and histological and biochemical alterations in the skin of tight
      skin mice.
AB  - Cutaneous hyperplasia observed in tight skin mice is due to a mutation located on
      chromosome 2. While homozygous mice die in utero, the heterozygotes survive. TSK
      syndrome is associated with the presence of autoantibodies specific for
      scleroderma target autoantigens. The presence of autoantibodies specific for
      topoisomerase I is characteristic of both human and murine disease. We have
      generated two distinct genotypes of mice, TSK/+ and +/+ with respect to the TSK
      trait by breeding TSK mice with immunodeficient mouse strains. Since the mutated
      gene of TSK syndrome has not yet been cloned, only histological and biochemical
      criteria were used for defining TSK genotype. In the F1 mice derived by mating
      TSK/+ mice with RAG2-/-, JH-/-, or C57BLvit/vit mice, we have found a good
      correlation between the amount of serum anti-topoisomerase I autoantibodies
      present and the histopathological and biochemical alterations that are
      characteristic of TSK scleroderma-like syndrome.

PMID- 8548838
TI  - Interaction of mouse thymocytes and a thymocyte-like cell line with the ECM
      glycoprotein entactin.
AB  - Entactin, a sulfated glycoprotein of 150-kDa, is a component of the extracellular
      matrix that promotes the adhesion of numerous types of cells, including
      lymphocytes (Li and Cheung, J. Immunol. 149, 3174, 1992), prompting us to
      question whether developing T lymphocytes in the thymus (thymocytes) also
      interact with this molecule. We thus investigated the adhesion of a thymocyte
      like cell line (S49.1) to entactin, as well as the adhesion and migration of
      primary mouse thymocytes upon entactin-coated surfaces. In dose-response and time
      course experiments, a 50 micrograms/mL coating concentration of entactin and a 60
      min incubation period induced a high level (approximately 65-85%) of S49.1 cell
      adhesion. Preincubation of the S49.1 cells in medium containing the metabolic
      inhibitors sodium azide or 2-deoxy-D-glucose inhibited adhesion to entactin 47.2
      and 79.5%, respectively. Furthermore, performing the adhesion assay at 4 degrees
      C instead of at 37 degrees C inhibited S49.1 cell adhesion 27.1%. A high
      percentage (approximately 90-100%) of S49.1 cells also bound to the lectin
      concanavalin A and to fibronectin, while laminin promoted only 19.3% adhesion.
      Our adhesion assay (St. John et al., J. Immunol. Methods, 170, 159, 1994) was
      then modified to permit a comparison of S49.1 cell adhesion strength to entactin
      relative to the other substrates. Consequently, Concanavalin A promoted the
      strongest adhesion, followed by fibronectin and then entactin. In addition, high
      percentages (92.5, 63, and 75.9%, respectively) of primary thymocytes from 4- to
      5-week-old BALB/c mice adhered to entactin, Con A, and fibronectin, while much
      lower levels (7.6%) of adhesion to laminin were observed. Using a capillary tube
      random migration assay to measure haptokinesis, entactin-, concanavalin A-, and
      fibronectin-coated surfaces stimulated little migration, while laminin-coated
      surfaces enhanced thymocyte migration extensively. Since entactin promoted
      thymocyte adhesion but affected migration only marginally, we suggest that this
      molecule may play a role in thymocyte localization during T cell development.

PMID- 8548839
TI  - Human lymphocyte responses against epitopes of a self antigen: a follow-up at
      different time points.
AB  - This study was aimed at examining the changes that may occur with time in the
      lymphocyte responses of an individual against peptide determinants of self
      antigens. Peripheral blood lymphocytes were collected from the same donor at
      seven different time points during a 10-month period and tested for their
      proliferative responses against whole human S-antigen and 40 overlapping peptides
      derived from the sequence of this uveitogenic retinal protein. Lymphocytes
      collected at different dates varied in their responsiveness to all tested
      antigens, as well as in the pattern of their response against individual
      peptides. The latter variability was expressed by differences in the hierarchical
      order of the most stimulatory peptides for lymphocytes collected at the seven
      time points. Despite the variability in their stimulatory capacity, six of the
      peptides exhibited their immunodominance by eliciting proliferation in
      lymphocytes collected at all time points. Our results thus indicate that data
      collected from a single sample of blood may be insufficient to accurately assess
      the level of cellular response to autologous antigens.

PMID- 8548840
TI  - Class I-like CD1A-C do not protect target cells from NK-mediated cytolysis.
AB  - Previous studies have validated the capacity of classical (HLA-A,B,C) and
      nonclassical (HLA-G) MHC class I antigens expressed by target cells to influence
      natural killer (NK) cell-mediated cytolysis. Generally, elevated expression of
      these HLA class I molecules is correlated with enhanced resistance to lysis by NK
      cells. In this study, we have evaluated the effect of transfected class I-like
      CD1A, CD1B, and CD1C molecules on C1R (HLA-A,B null) target cell sensitivity to
      natural killing. We report that while each of these molecules was expressed at
      physiologically relevant levels on the cell surface of clonal transfectants, no
      change was observed in target cell susceptibility to fresh or lymphokine
      activated NK-mediated lysis.

PMID- 8548841
TI  - Expression and function of low-density lipoprotein receptors in CD3-CD16+CD56+
      cells: effect of interleukin 2.
AB  - Low-density lipoprotein receptors (LDLR) have been shown to be expressed,
      internalized, and transcribed in CD3-CD16+CD56+ cells. Only a low percentage (up
      to 12%) of NK cells express LDLR. Interleukin 2 (IL-2) (1000 IU/ml) induced a
      threefold increase in the expression of LDLR on the cell surface that results
      from, at least in part, augmentation of LDLR turnover from the cytosol to the
      membrane. Scatchard analysis revealed that IL-2 decreased the Kd of LDLR binding
      for LDL from 7.53 to 4.33 nM with an increment in the number of binding sites
      from 2500 up to 5000. Both the proliferative response and cytotoxic functions of
      these cells are affected by LDL. Low concentrations of LDL induce an increase in
      the proliferative response (up to eightfold) and in the cytotoxic response of NK
      cells (up to fivefold). High concentration (more than 60 micrograms/ml) of LDL
      hampers both proliferative response and cytotoxic activity of NK cells. LDL did
      not affect the cytotoxic functions of IL-2-activated NK cells. Overall, we have
      shown that LDLR is expressed on the surface of NK cells and can be augmented by
      IL-2. Furthermore, we propose some insights into the mechanism responsible for
      the enhanced expression of LDLR on NK cell surface. In addition, our data clearly
      delineate that LDLR plays an important role in the regulation of proliferative
      responses and cytotoxic activity of these cells.

PMID- 8548842
TI  - Effect of injection of anti-CD4 and anti-CD8 monoclonal antibodies on the
      development of experimental systemic lupus erythematosus in mice.
AB  - Induction of an experimental disease resembling systemic lupus erythematosus
      (SLE) has been achieved in mice by immunization with a human monoclonal anti-DNA
      antibody, bearing a common idiotype, designated 16/6 Id. In the present study we
      used anti-CD4 and anti-CD8 antibodies to modulate the induction and development
      of the experimental disease. Thus, depletion of CD4+ T cells prior to the
      immunization with the 16/6 inhibited the induction of experimental SLE. In
      contrast, injection of anti-CD4 antibodies to mice that were already immunized
      with the 16/6 Id did not prevent the development of the disease. Furthermore,
      administration of anti-CD8 antibodies either before or after priming with the
      16/6 Id increased the serological and clinical manifestations of the disease.
      These results demonstrate the pathogenic role of CD4+ and CD8+ T cells in the
      induction and development of the experimental SLE.

PMID- 8548843
TI  - Liver injury model in mice induced by a cellular immunologic mechanism--delayed
      type hypersensitivity-induced liver injury to picryl chloride and phenotype of
      effector cell.
AB  - Liver injury was induced in BALB/c mice by local delayed-type hypersensitivity
      (DTH) to picryl chloride (PC1). Distinct changes of biochemical parameters were
      observed including the elevation of serum alanine and aspartate
      aminotransferases, increase of liver lipid peroxides, as well as decrease of
      serum alkaline phosphatase. Damage was confirmed by histopathological findings
      such as hepatocellular necrosis, granulocyte infiltration, and fatty
      degeneration. The liver injury was passively transferred into naive syngeneic
      mice by infusing spleen cells from immune mice. The capacity of the splenocytes
      to induce liver injury in recipient mice was almost completely abolished by
      pretreatment of the cells with anti-Thy 1.2 or anti-CD4, but not anti-CD8
      antibody. These findings suggest that the production of liver injury by a local
      DTH mechanism is possible and the subpopulation of T cells, Thy-1.2+, L3T4+, and
      Lyt-2- cells, is at least one of the effector cells that mediate the injury.

PMID- 8548844
TI  - Plasticity of the T cell receptor repertoire in TCR beta-chain transgenic mice.
AB  - The potential alpha beta T cell receptor (TCR) repertoire in normal mice is
      extremely large and estimated by M. M. Davis and P. J. Bjorkman (Nature 334, 395,
      1988) to include 5.2 x 10(18) different receptor molecules. This tremendous
      diversity provides the basis for T cell recognition of the universe of antigens
      including bacterial, viral, and allogeneic epitopes. Expression of a single TCR
      beta-chain transgene should alter the repertoire by limiting the available
      diversity, therefore, creating holes in the repertoire or producing TCR with
      decreased affinity. To determine the effect of drastically decreasing the size of
      the repertoire, we investigated T cell responses in TCR beta-chain transgenic
      mice expressing the V beta 8.2 transgene. Previous results showed that > 98% of T
      cells in these mice express the transgene; thus, the TCR repertoire is reduced by
      orders of magnitude. We tested the T cell responses of the transgenic mice and
      nontransgenic littermates to nine different MHC haplotypes in mixed lymphocyte
      reactions, five protein antigens, and eight immunogenic peptides. Surprisingly,
      the transgenic mice responded to all antigenic stimuli tested indicating the lack
      of a hole in the TCR repertoire. Interestingly, however, the response in every
      case was quantitatively lower than the response by the nontransgenic littermates.
      In contrast, transgenic and nontransgenic T cells responded equivalently to
      stimulation with mitogens or to stimulation with immobilized alpha-TCR mAb
      indicating that the transgenic T cells had a normal capacity to respond. To
      differentiate between decreased TCR affinity and decreased precursor frequency,
      we performed a limiting dilution analysis to the peptide antigens CI:NP and
      OVA324-339. The results showed approximately a three-to eight-fold decrease in
      the frequency of transgenic T cells responding to the peptide compared to
      nontransgenic littermates. We previously showed that the response to cI84-98 and
      PLP could be blocked with anti-V beta 8 mAb indicating that V beta 8.2-bearing T
      cells are capable of responding to peptide antigen. Analysis of TCR V alpha chain
      expression by PCR and flow cytometry showed similar V alpha expression in both
      the transgenic and the nontransgenic mice. These results demonstrate tremendous
      plasticity in the TCR repertoire permitting T cell responses by the transgenic
      mice to all antigens tested. However, the decreased magnitude of the responses
      may impair the capacity to defend against natural pathogens. Therefore, although
      the large TCR repertoire of normal mice may not be necessary to produce in vitro
      responses to many experimental antigens, it may confer survival benefits in
      natural environments.

PMID- 8548845
TI  - The CD45RB-associated epitope defined by monoclonal antibody CZ-1 is an
      activation and memory marker for mouse CD4 T cells.
AB  - Monoclonal antibody CZ-1 defines a novel sialic acid-dependent CD45RB-associated
      epitope. The CZ-1 antigen is expressed on the subpopulation of CD4 T cells that
      proliferate in response to IL-2. Because IL-2 responsiveness often denotes T cell
      activation, we examined the expression of the CZ-1 antigen on CD4 T cells taken
      from mice at various times during an infection with lymphocytic choriomeningitis
      virus (LCMV). The blast-sized CD4 T cells at Day 6 postinfection were CZ-1+.
      Further cell surface phenotyping showed that those blast cells activated at Day 6
      postinfection were CD45RBdimPgp-1brightMEL-14-. This contrasts with the CZ-1
      CD45RBbrightPgp-1bright/dimMEL-14+ resting cell population prior to infection. To
      determine if memory CD4 T cells continued to express the CZ-1 epitope long after
      resolution of the LCMV infection, CD4+CZ-1+ and CD4+CZ-1- populations were
      purified by cell sorting and placed in an in vitro proliferation assay with LCMV
      infected antigen-presenting cells. It was found that the CD4+CZ-1+ population
      contained virtually all of the virus-specific memory. The CZ-1 epitope is
      therefore both an activation and a memory marker for murine CD4 T cells.

PMID- 8548846
TI  - Divergent phosphotyrosine signaling via Fc gamma RIIIA on human NK cells.
AB  - Previous studies have indicated that interaction of Fc gamma RIIIA on natural
      killer (NK) cells with various immunoglobulin ligands or monoclonal antibodies
      (mAbs) can have either stimulatory or inhibitory effects on cytotoxic activity,
      but the basis for such divergent functional effects has been unclear. We report
      here that stimulation of NK cells via Fc gamma RIIIA by monoclonal anti-human
      CD16 (3G8), monomeric IgG (mIgG), or dimeric IgG (dIgG), used either alone or
      cross-linked by secondary Ab (goat anti-mouse IgG or goat anti-human IgG),
      resulted in different phosphotyrosine protein patterns. These results suggest
      that distinct substrates are involved in signaling pathways activated via various
      agonists of the same triggering surface molecule. Three protein tyrosine kinases,
      i.e., LCK, LYN, and SYK, were activated by occupancy of the Fc gamma RIIIA, and
      only LCK activity showed a divergence in effects induced by the various ligands,
      with strong autophosphorylation induced by mIgG upon cross-linking. We observed
      no ligand-induced activation of p59fyn, p60c-src, or p62c-yes, src-related
      protein tyrosine kinases which are expressed in NK cells. Activity of
      phosphatidylinositol 3-kinase (PI 3-kinase) induced by receptor-specific
      antibodies or IgG ligands had different kinetics while the level of cytoplasmic
      free calcium was greatest upon 3G8-induced stimulation. Although the changes in
      kinase activities associated with Fc gamma RIIIA-mediated regulation of NK cells
      are complex, it appears that the patterns induced varied with the nature of the
      ligand and the direction of the regulation of NK activity.

PMID- 8548847
TI  - Bacterial DNA induces murine interferon-gamma production by stimulation of
      interleukin-12 and tumor necrosis factor-alpha.
AB  - Bacterial, but not mammalian DNA, can induce interferon-gamma (IFN-gamma) in
      murine splenocytes. To elucidate the basis of this activity, we have assessed in
      vitro cytokine production by C3H/HeJ splenocytes stimulated with either DNA from
      Escherichia coli or a synthetic oligonucleotide containing an active palindromic
      sequence identified from DNA. Both DNAs induced IFN-gamma production, with the
      requirement for intact DNA shown by sensitivity to DNase digestion. Fractionated
      cell populations were evaluated to determine direct or indirect cellular effects
      of the DNA. Although bacterial DNA failed to induce IFN-gamma in the nonadherent
      cell population, supernatants from adherent cells stimulated by DNA induced IFN
      gamma production by these cells. Interleukin-12 (IL-12) was detectable in
      supernatants from DNA-stimulated splenocytes before IFN-gamma, and neutralizing
      antibodies directed against IL-12 markedly inhibited the induction of IFN-gamma.
      Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies also inhibited IFN-gamma
      production, and the combination of both anti-IL-12 and anti-TNF-alpha could
      totally inhibit production of IFN-gamma. Taken together, these results indicate
      that the stimulation of IFN-gamma production by bacterial DNA is mediated by IL
      12 and TNF-alpha and point to macrophages/monocytes as targets of action of this
      macromolecule.

PMID- 8548848
TI  - Modulation of endothelial cell expression of ICAM-1, E-selectin, and VCAM-1 by
      beta-estradiol, progesterone, and dexamethasone.
AB  - The aim of this study was to examine the effects of beta-estradiol, progesterone,
      and dexamethasone on cytokine-stimulated endothelial cell expression of adhesion
      molecules. TNF-alpha (250 U/mL) and IL-1 alpha (50 U/mL) were used to stimulate
      the endothelial cells for 6 or 23 hr in vitro. Indirect immunofluorescence and
      flow cytometry were used to quantitate expression of adhesion molecules. After 6
      hr stimulation with TNF-alpha increased expression of E-selectin (P < 0.03) was
      noted with beta-estradiol. Strong suppression of ICAM-1 (P < 0.005) and E
      selectin (P < 0.005) expression was evident with dexamethasone, which did not
      influence VCAM-1 expression. After 6 hr stimulation with IL-1 alpha suppression
      of E-selectin was observed with progesterone (P < 0.001). Dexamethasone had
      strong suppressive effects on ICAM-1 (P < 0.001), E-selectin (P < 0.0001), and
      VCAM-1 (P < 0.0002). After 23 hr stimulation with IL-1 alpha or TNF-alpha none of
      the examined steroids showed a significant effect on the fluorescence intensity
      of adhesion molecules, although there was a slight increase of the percentage of
      ICAM-1 positive cells with high concentrations of beta-estradiol after
      stimulation with TNF-alpha. Beta-estradiol and progesterone are modulatory
      factors of E-selectin expression on endothelial cell in vitro. Dexamethasone
      reduces adhesion molecule expression over endothelial cells after cytokine
      stimulation. These effects may be important in understanding the role of these
      steroids in autoimmune diseases.

PMID- 8548849
TI  - Treatment of Candida albicans mannan-specific downregulatory cell populations
      with divergent concentrations of monophosphoryl lipid A and intact
      lipopolysaccharide in vitro abrogates their effect on delayed hypersensitivity.
AB  - We have shown previously that splenocytes from mice injected with Candida
      albicans mannan (MAN) suppress MAN-specific delayed hypersensitivity (DH) when
      transferred to immunized recipients and that treatment of donor mice with
      monophosphoryl lipid A (MLA) derived from Salmonella typhimurium or Salmonella
      minnesota shortly before transfer abrogated the downregulatory activity. We now
      show that treatment of splenocytes in vitro at 4 degrees C with 5 ng/ml MLA or
      0.05 ng/ml S. typhimurium lipopolysaccharide (LPS) for 30 min before transfer
      also abrogated downregulatory activity. Higher or lower doses of MLA, 5
      micrograms or 5 pg, appeared to increase the suppressor activity slightly (5
      micrograms) or had no effect (5 pg). LPS induced similar effects but the
      concentrations of LPS required to show the effects were 100-fold less than those
      of MLA. The effect of MLA appeared to be on cell(s) in the transfer population
      involved in MAN-specific DH, in that spleen cells from normal mice treated with
      MLA prior to transfer had no effect on DH. Finally, the population of MLA
      responsive cells mediating downregulation could not be concentrated on MLA-coated
      plates, suggesting that the MAN-specific downregulatory cell(s) either did not
      bind to MLA or did not bind to MLA with sufficient avidity to remain attached
      during the washing procedures. The feasibility of abrogating suppression by
      treatment of lymphoid cells in vitro will allow a more detailed analysis of the
      mechanism of abrogation.

PMID- 8548850
TI  - IL-10 stimulates murine antigen-driven antibody responses in vitro by regulating
      helper cell subset participation.
AB  - The effects of IL-10 on in vitro antigen-driven murine antibody responses and
      helper cell IL-4 and IFN-gamma secretory capacity were investigated. Low antigen
      concentrations stimulated high responses in all antibody isotypes examined; IgD
      was not assayed. Under these conditions, exogenous IL-10 minimally potentiated
      synthesis of antigen-specific IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA, but
      inhibited antigen-specific IgE secretion. High antigen levels stimulated antigen
      specific IgM, IgG2a, and IgG2b responses, but inhibited synthesis of all other
      isotypes. In high antigen cultures, IL-10 augmented secretion of antigen-specific
      antibody in all isotypes except IgE. Essentially all of the antibody produced in
      the presence of high or low antigen concentrations was antigen-specific.
      Exogenous IL-10 substantially stimulated production of antigen-nonspecific
      antibody in all isotypes except IgG3. IL-10 allowed for greater Ig+ cell yield;
      comparable numbers of CD4+ and CD8+ cells were observed in the presence or
      absence of IL-10 in culture. The stimulatory effects of IL-10 for in vitro
      antibody responses were observed during a limited period of time after in vivo
      antigen priming of the responding cell populations. In contrast, IL-10 inhibited
      IgE synthesis at all time points tested. Low concentrations of antigen maintained
      the in vitro capacity of helper cells to secrete IL-4, while high antigen
      concentrations did not. Exogenous IL-10 potentiated IL-4 secretory capacity in
      high antigen cultures. The capacity for IFN-gamma secretion was comparable in
      high and low antigen cultures and exogenous IL-10 significantly inhibited such
      capacity under both sets of conditions. We conclude that IL-10 is generally
      stimulatory for murine antibody responses in vitro, with the possible exception
      of antigen-specific IgE. Such stimulatory effects appear to reflect increased
      activity of type 2 helper cells with concurrent decrease in type 1 helper cell
      activity.

PMID- 8548851
TI  - Lysis of human tumor cell lines by canine complement plus monoclonal
      antiganglioside antibodies or natural canine xenoantibodies.
AB  - Because certain antiganglioside monoclonal antibodies can facilitate antibody
      dependent cellular cytotoxicity against GD2+ ganglioside-bearing human and canine
      tumor cells, we wished to determine if clinically relevant antiganglioside
      monoclonal antibodies (Mabs) could also fix canine complement to lyse tumor cells
      in vitro. Using flow cytometry, human tumor cell lines (M21 melanoma and OHS
      osteosarcoma) were shown to highly express ganglioside GD2 and, to a lesser
      degree, GD3. In 51Cr release assays, M21 cells were lysed with canine serum, as a
      source of complement, plus either Mab 14.G2a or its mouse-human chimera, ch
      14.18, specific for GD2. Heating canine serum abrogated its lytic activity and
      addition of rabbit complement reconstituted M21 lysis. Similar results were
      obtained with M21 cells when Mab R24 (against GD3) and canine serum were used.
      OHS cells were also lysed with canine serum plus Mab 14.G2a and lytic activity
      was abolished by heating canine serum but reconstituted with rabbit complement.
      Alone, canine serum or Mabs were not lytic to M21 or OHS cells. Conversely, human
      neuroblastoma (LAN-5) and K562 erythroleukemia cells were lysed by canine serum
      alone which was shown by flow cytometry to contain naturally occurring canine IgM
      antibodies that bound LAN-5 and K562 cells. The lytic activity of canine serum
      for LAN-5 or K562 cells was abolished by heating and restored by addition of
      either human or rabbit complement. Thus, human tumor cell lines can be lysed with
      antiganglioside Mabs through fixation and activation of canine complement
      dependent lytic pathways. Canine xenoantibodies also mediate complement-dependent
      cytotoxicity of some human tumor cell lines. Together, these results are
      significant because they demonstrate an antitumor effect of the canine immune
      system which is of potential importance for cancer immunotherapy in a promising
      animal model.

PMID- 8548852
TI  - Toxicology of halogenated aliphatic hydrocarbons: structural and molecular
      determinants for the disturbance of chromosome segregation and the induction of
      lipid peroxidation.
AB  - The induction of mitotic chromosome malsegregation, mitotic arrest and lethality
      by a set of 55 halogenated hydrocarbons was investigated. To this aim, genetic
      assays in the mould Aspergillus nidulans, able to provide precise quantitative
      information on the end-points studied, were used throughout the work. The
      experimental data obtained were used to develop QSAR models for the induction of
      aneuploidy, which pointed to a major role of electrophilicity as molecular
      determinant for the aneugenic potential of the halogenated hydrocarbons
      investigated. Within the hypothesis of a link between the electrophilicity of
      haloalkanes and their propensity to undergo a reductive biotransformation, with
      production of free radical species, a subset of 27 compounds was also tested for
      the ability to induce lipid peroxidation in rat liver microsomes in vitro. The
      results obtained indicate a partial coincidence between the abilities to initiate
      lipid peroxidation and to disturb chromosome segregation at mitosis. The data
      base obtained was also used to investigate the relationship between chemical
      structure and peroxidative potential. The analysis indicated that electronic and
      structural parameters related to the ease of homolitic cleavage of the carbon
      halogen bond play a pivotal role as determinants for the peroxidative character
      of haloalkanes.

PMID- 8548853
TI  - Marchantinquinone, isolated from Reboulia hemisphaerica, as inhibitor of lipid
      peroxidation and as free radical scavenger.
AB  - The antioxidant effect of marchantinquinone was studied using various models.
      Marchantinquinone inhibited Fe(2+)-induced lipid peroxidation in rat brain
      homogenate in a concentration-dependent manner with an IC50 15.3 +/- 2.9 microM.
      Marchantinquinone was less effective than alpha-tocopherol and BHT in reducing
      the stable free radical diphenyl-2-picrylhydrazyl (DPPH). The IC0.200 were 37.5
      +/- 2.5, 9.2 +/- 1.6 and 14.5 +/- 2.5 microM, respectively. Marchantinquinone
      also scavenged peroxyl radical derived from 2,2'-azobis(2
      amidinopropane)dihydrochloride (AAPH) in aqueous system with a stoichiometric
      factor of 0.9 +/- 0.1. Furthermore, it prevented conjugated-diene formation and
      apolipoprotein B (apo B) oxidation of LDL. However, marchantinquinone did not
      chelate Fe2+ or possess superoxide anion and hydroxyl radical scavenging
      activity. It also did not scavenge 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN)
      derived peroxyl radical in hexane. These results indicate that marchantinquinone
      may be an effective antioxidant and can protect rat brain homogenate and LDL
      against oxidation.

PMID- 8548854
TI  - Signal transduction mechanism in response to aflatoxin B1 exposure:
      phosphatidylinositol metabolism.
AB  - A single dose of aflatoxin B1 (7 mg/kg body weight) to male Wistar rats
      significantly stimulated the hepatic activity of phosphatidylinositol kinase, a
      key enzyme in the cell signalling mechanism, 1-7 h following its administration.
      Phosphatidylinositol 4-phosphate kinase activity showed only marginal increase,
      whereas activities of diacylglycerol kinase and phosphatidylinositol synthetase
      remained unchanged. The level of diacylglycerol, however, recorded a sharp
      increase at 1 and 2 h after carcinogen treatment. The stimulation of
      phosphatidylinositol cycle with faster turnover of active second messengers might
      be an early step in the manifestation of toxicity and/or carcinogenicity.

PMID- 8548855
TI  - 32P-postlabelling analysis of adducts formed by mitoxantrone and ametantrone with
      DNA and homopolydeoxyribonucleotides after enzymatic activation.
AB  - DNA adduct formation by enzymatically activated mitoxantrone and ametantrone has
      been studied by 32P-postlabelling method. Both drugs were activated by
      peroxidase/hydrogen peroxide system and formed several DNA adducts when reacted
      with calf thymus DNA. Mitoxantrone gave 3 and ametantrone 4 different DNA adducts
      with apparently similar chromatographic features suggesting that DNA adducts
      formed by both compounds do not differ significantly in their chemical structure.
      Despite this similarity, the level of DNA modification is 10 times higher for
      mitoxantrone compared to ametantrone. We did not observe DNA adducts in control
      samples where both drugs were incubated with DNA in the absence of the activating
      system. It indicates the importance of oxidative activation of mitoxantrone and
      ametantrone for their ability to bind covalently DNA. In order to identify
      nucleobases involved in the formation of DNA adducts by anthracenediones,
      polydeoxyadenosine, polydeoxythymidine, deoxyguanosine 3'-monophosphate and
      deoxycytosine 3'-monophosphate were modified by mitoxantrone and ametantrone
      activated in the above mentioned oxidating system. We proved that the only
      nucleobase modified by both drugs is guanine with no alkylation observed at other
      DNA bases. The pattern of adducts formed with deoxyguanosine 3'-monophosphate is
      reminiscent of that obtained with calf thymus DNA. In addition, mitoxantrone was
      found to be phosphorylated during the postlabelling procedure, most probably at
      the 1,4-hydroxyl groups of the chromophore. Ametantrone which does not possess
      hydroxyl groups attached to the chromophore core was resistant to phosphorylation
      by T4 polynucleotide kinase and gamma-[32P]ATP. These results for the first time
      provide direct evidence that mitoxantrone and ametantrone form DNA adducts when
      activated by oxidation in vitro.

PMID- 8548856
TI  - Analysis of the reactivity of [14C]toluene diisocyanate (TDI) in an isolated,
      perfused lung model.
AB  - An isolated, perfused, guinea pig lung model was used to investigate the
      molecular events which occur when a 14C-labeled TDI vapor reaches the airways.
      Exposure concentrations of 0.2 and 0.7 ppm were tested. Perfusate composition
      included: Krebs Ringer buffer only, as well as buffer containing either guinea
      pig serum albumin, human serum albumin, or diluted guinea pig plasma.
      Radioactivity was detected in the perfusate within minutes of exposure, and
      following a delay, increased linearly. The rate of uptake was dependent on TDI
      concentration and the composition of the perfusate. Biochemical characterization
      of the state of the 14C-labeled material in the perfusate was performed. The
      distribution between low and high molecular weight reaction products was
      determined by molecular sieve fractionation and varied as a function of perfusate
      composition but no variability was observed as a function of time during the 45
      min of exposure. An increase in nucleophile concentration in the perfusate was
      associated with both a higher percentage of conjugated products (from 15% with
      buffer only to 45% with diluted guinea pig plasma) and an increase in the rate of
      TDX uptake (from 0.5 microns Eq/min with buffer alone to 0.1 micrograms Eq/min
      with diluted GPSA as perfusate at 0.7 ppm). GC-MS analysis of the samples for
      free TDA, before and after acid hydrolysis, showed that the low molecular weight
      product(s), which represented from 55-85% of the circulating radioactivity, was
      composed of hydrolyzable and non-hydrolyzable conjugates and metabolites with
      approximately 4% of the label associated with free TDA. Although the distribution
      between high and low molecular weight species varies, this result is analogous to
      the findings from in vivo studies and suggests that the isolated, perfused lung
      (IVPL) system may be a useful tool in investigating the molecular mechanisms of
      isocyanate-induced disease and metabolic activity of the lung.

PMID- 8548857
TI  - Comparative toxicity of 2-hydroxy-3-alkyl-1,4-naphthoquinones in rats.
AB  - 2-Hydroxy-1,4-naphthoquinone has previously been shown to cause severe haemolytic
      anaemia and renal tubular necrosis in animals. In order to establish if such
      toxic effects are common to other 2-hydroxynaphthoquinone derivatives, the short
      term toxicity of a number of 2-hydroxy-3-alkyl-1,4-naphthoquinones has been
      compared in rats. 2-Hydroxy-3-methyl, 2-hydroxy-3-ethyl- and 2-hydroxy-3-propyl
      1,4-naphthoquinone were found to cause both haemolysis and renal damage, although
      the severity of the changes provoked by these substances was much lower than
      those induced by the parent compound at an equivalent dose-level. Furthermore,
      the toxicity of the hydroxy-alkylnaphthoquinones decreased with increasing size
      of the alkyl substituent and no toxic changes were recorded in animals dosed with
      2-hydroxy-3-butyl- or 2-hydroxy-3-pentyl-1,4-naphthoquinone. The relationship
      between the in vivo effects of these substances and previously reported data on
      their in vitro cytotoxicity is discussed in relation to the mechanism of toxicity
      of these and other naphthoquinone derivatives.

PMID- 8548858
TI  - In vitro metabolism of 5-fluoro-2-glutathionyl-nitrobenzene by kidney proximal
      tubular cells studied by 19F-NMR.
AB  - Proximal tubular biotransformation of the glutathionyl (GSH) conjugate derived
      from 2,5-difluoronitrobenzene (5-fluoro-2-glutathionyl-nitrobenzene) was studied
      by means of 19F-NMR. This method allows a direct and specific detection of the
      fluorinated metabolites formed, at a detection limit of 1 microM for an overnight
      NMR run. Incubation of a monolayer of LLCPK1 cells with 100 microM 5-fluoro-2
      glutathionyl-nitrobenzene for 24 h showed that these cells metabolize this GSH
      conjugate into the corresponding cysteinylglycyl and cysteine conjugate. The
      expected N-acetylcysteine conjugate however was not formed as an endproduct.
      Additional experiments demonstrated the absence of N-acetyltransferase activity
      in LLCPK1 cell lysates incubated with FCysNB and also the rapid loss of this
      activity in isolated renal proximal tubular cells (RPT): freshly isolated RPT
      cells do convert FCysNB to FNAcNB as major metabolite but, upon cultivation,
      quickly lose this capacity. Since uptake of FCysNB might also be a limiting
      factor, we investigated transport of FCysNB from the apical to the basolateral
      side of the culture RPT cells. No indication for such transport was obtained.
      Thus, the absence of mercapturic acid formation in LLCPK1 cells and cultured RPT
      cells is the results of a decline in N-acetyltransferase activity and perhaps a
      deficient cellular uptake of the cysteine conjugate.

PMID- 8548859
TI  - Lead-binding proteins in brain tissue of environmentally lead-exposed humans.
AB  - This study reports the partial purification and characterization of cytosolic
      lead binding proteins (PbBPs) in human brain tissue of environmentally Pb-exposed
      subjects. The isolated proteins were initially characterized based upon the
      presence of endogenously associated Pb. Following partial purification (Sephadex
      G-75 and A-25 DEAE anion-exchange chromatography), the isolated PbBPs (contained
      within a single DEAE peak) showed a single class of high affinity binding sites
      with an apparent Kd of 10(-9) M, based upon competition assays using radioactive
      203Pb and Hill and Scatchard analysis. The presence of endogenously bound Pb with
      the isolated proteins indicated the association of Pb with the protein(s) in vivo
      in these environmentally Pb-exposed subjects, since the samples were prepared in
      an ultraclean lead analysis laboratory. Moreover, the persistence of Pb-protein
      binding throughout the initial two steps (Sephadex G-75 and A-25 DEAE) of the
      purification scheme is consistent with the high affinity and stability of binding
      measured with the radiolead competition assays. The DEAE isolated PbBPs were
      further purified by denaturing reversed-phase HPLC analysis, resulting in the
      isolation of two proteins, thymosin beta 4 (5 kDa, pI 5.1) and a second as yet
      unidentified protein with an approximate molecular mass of 20 kDa and a pI of
      5.9. Qualitative 203Pb-binding analysis of these HPLC purified proteins suggested
      that they may be primarily responsible for the observed Pb binding in the single
      DEAE peak. Nearly identical results were obtained in brain cytosols from male and
      female, and young and adult individuals, although further quantitative analyses
      are needed to investigate possible sex and age relationships. These data are
      significant because they contribute to a better understanding of the presence of
      PbBPs in a sensitive target organ for Pb toxicity in humans, suggesting a
      possible role of these or similar proteins as sensitive biomarkers of Pb exposure
      and toxicity.

PMID- 8548860
TI  - Inhibition of the conversion of pre-interleukins-1 alpha and 1 beta to mature
      cytokines by p-benzoquinone, a metabolite of benzene.
AB  - Chronic exposure of humans to benzene causes severe bone marrow cell depression
      leading to aplastic anemia. Marrow stromal macrophage dysfunction and deficient
      interleukin-1 production has been reported for patients with severe aplastic
      anemia. The stromal macrophage, a target of benzene toxicity, is involved in
      hematopoietic regulation through the synthesis of several cytokines including
      interleukin-1, which is required for production by stromal fibroblasts of a
      number of cytokines required for the survival of hematopoietic progenitor cells.
      We have previously demonstrated that hydroquinone, a major toxic metabolite of
      benzene in marrow, prevents the proteolytic conversion of 31 kDa pre-interleukin
      1 alpha to the 17 kDa cytokine by calpain in purified murine stromal macrophages.
      Furthermore, stromal macrophages from benzene-treated mice produce the 31 kDa pre
      interleukin-1 alpha when stimulated in culture with endotoxin, but cannot convert
      the precursor to interleukin-1 alpha. In this report, we show that 1,4
      benzoquinone, the oxidation product of hydroquinone in the cell, causes a
      concentration-dependent inhibition of highly purified human platelet calpain with
      an IC50 of 3 microM. Hydroquinone also inhibits the processing of pre-interleukin
      1 beta by interleukin-1 beta convertase. The addition of 2 microM hydroquinone to
      B1 cells that undergo autocrine stimulation by interleukin-1 beta resulted in the
      cessation of autocrine cell growth and interleukin-1 beta secretion into the
      culture medium, as determined by Western immunoblots of the culture supernatants.
      Purified converting enzyme treated with 3 microM benzoquinone was incapable of
      converting 31 kDa recombinant pre-interleukin-1 beta to the 17 kDa mature
      cytokine as analyzed by polyacrylamide gel electrophoresis and Western
      immunoblotting. These findings support our observations in a mouse model that
      benzene-induced bone marrow cell depression results from a lack of interleukin-1
      alpha subsequent to an inhibition by benzoquinone of calpain, the protease
      required for converting pre-interleukin-1 alpha to active cytokine. The results
      may provide a basis for studying benzene-induced aplastic anemia in a mouse
      model.

PMID- 8548861
TI  - Cholesterol interaction with free radicals produced from carbon tetrachloride or
      bromotrichloromethane by either catalytic decomposition or via liver microsomal
      activation.
AB  - The reaction between cholesterol (Ch) and trichloromethyl or trichloromethyl
      peroxyl radicals was studied. The latter were generated from CCl4 either by
      benzoyl peroxide (BP) catalysis or via thermal activation or by liver microsomal
      NADPH-dependent biotransformation of CBrCl3. The structure of the products formed
      was elucidated by gas chromatography-mass spectrometry (GC/MS). Under aerobic
      conditions and using thermal activation of CCl4, the formation of 6 products was
      observed. Two (I and II) were dehydrated Ch derivatives (one also having a third
      double bond) (I). Another product was a delta(5)-3 ketone derivative of Ch (III).
      Two additional reaction products were determined as ketocholesterols (IV and V).
      One chloro Ch was also formed (VI). At low concentrations of BP, reaction was
      more extensive than under thermal activation, and the formation of peaks I to IV
      was also observed. When the reaction was conducted anaerobically and using
      thermal activation of CCl4 to generate radicals, only products I and II were
      formed in low yield. Under anaerobic conditions, but using catalyst, compounds I
      and III were produced plus two new isomeric ketocholesterol derivatives (VIII and
      IX) and also a compound having an extra hydroxyl group on the Ch structure (X).
      In order to check whether similar reactions are observable under biological
      experimental conditions, we used activation of CBrCl3 by liver microsomes. The
      incubation using only microsomes (without CBrCl3 or NADPH) showed two
      ketocholesterol peaks (A and B). In the presence of CBrCl3 we could detect peak B
      and hydroxycholesterol (C) and two others, ketocholesterols (D and E). D was the
      only peak showing close similarity (spectrum and retention time) to one of those
      observed in the chemical reaction system (V). The reaction of CBrCl3 in the
      presence of NADPH showed peaks B, C, D and E, in low abundance and a 7
      ketocholesterol (F). If some of the reaction products reported here were formed
      during the intoxication with these haloalkanes, significant biological
      consequences might be expected.

PMID- 8548862
TI  - 3,5-Disubstituted analogues of paracetamol. Synthesis, analgesic activity and
      cytotoxicity.
AB  - Seven 3,5-disubstituted analogues of paracetamol were synthesised in order to
      compare their physicochemical, pharmacological and toxicological properties with
      those of paracetamol (4'-hydroxyacetanilide, acetaminophen). Oxidation of the
      phenolic structure is likely involved in the analgesic action of paracetamol as
      well as in its toxification by cytochrome P450. The effect of disubstitution
      adjacent to the phenolic hydroxyl group was studied in order to establish
      possible structure-activity relationships. 3,5-Substituents with electron
      donating capacities (R = -CH3, -OCH3, -SCH3) decreased the half-wave oxidation
      potential substantially by 0.07 V to 0.16 V, whereas electron-withdrawing
      substituents (R = -F, -Cl, -Br, or -I) increased the oxidation potential by 0.04
      V to 0.06 V when compared to paracetamol. Electron-donating substituents (R = 
      CH3, -OCH3, -SCH3) increased the mouse brain cyclooxygenase inhibiting capacity
      of paracetamol. Electron-withdrawing halogen substituents (R = -F, -Cl, -Br or 
      I) decreased this inhibiting capacity. In agreement with this, the in vivo
      analgesic activity of the 3,5-dihalogenated analogues was lower when compared to
      paracetamol. Electron-donating substituents (R = -CH3, -OCH3, -SCH3) decreased
      the cytotoxicity of paracetamol, when measured as leakage of lactate
      dehydrogenase from freshly isolated rat hepatocytes, almost completely. Most 3,5
      dihalogen substituents (R = -F, -Cl or -Br) diminished it slightly. The fourth
      electron-withdrawing substituent (R = -I) strongly lowered the cytotoxicity of
      paracetamol in this test system. In conclusion, a higher cycylooxygenase
      inhibitory potency of 3,5-disubstituted analogues of paracetamol seemed to
      correlate with a lower cytotoxicity. 3,5-Disubstituted analogues with electron
      donating substituents might therefore be safer analgesics than paracetamol
      itself. The opposite probably applies to analogues of paracetamol with electron
      withdrawing substituents at the 3- and 5- positions of the aromatic nucleus.

PMID- 8548863
TI  - Platinum(II) complexes containing iminoethers: a trans platinum antitumour agent.
AB  - The biological activity of cis and trans complexes of formula [PtCl2(HN =
      C(OMe)Me)2] has been investigated. The iminoether ligands can have either E or Z
      configuration about the C = N double bond, therefore EE, EZ and ZZ isomers are
      obtainable. Substitution of iminoether with EE configuration for amine leads to
      unexpectedly high antitumor activity for the complex with trans geometry which
      turns out to be more active than the cis congener in the P388 leukaemia system.
      The same trans-EE complex shows an activity comparable to that of cisplatin in
      reducing the primary tumour mass and lung metastases in mice bearing Lewis lung
      carcinoma, thus representing a trans platinum complex active on both
      limphoproliferative and solid metastasizing murine tumours. Also the
      cytotoxicity, the inhibition of DNA synthesis and the mutagenic activity, which
      are greater for the cis- with respect to the trans-isomer in the amine complexes,
      are instead greater for the trans- than for the cis- isomer in the case of
      iminoether compounds. Binding to calf thymus DNA is slower for iminoether
      complexes than it is for amine complexes, however after 24 h reaction time the
      level of binding is similar for both types of complexes. Trans-EE, like trans
      DDP, does not give the DNA conformational alterations (terbium fluorescence)
      typical of antitumour-active cis- platinum compounds, but, under strictly
      analogous experimental conditions, shows a greatly reduced DNA interstrand cross
      linking ability (heat denaturation/renaturation assay) with respect to either
      trans-DDP or cis-EE and cis-DDP. The data in hand point to a new trans platinum
      antitumour complex with a mechanism of action different from that of cis-DDP and
      classical analogues.

PMID- 8548864
TI  - Oxidative stress in fish exposed to model xenobiotics. Oxidatively modified forms
      of Cu,Zn-superoxide dismutase as potential biomarkers.
AB  - Fish (Sparus aurata) were intraperitoneally injected with model xenobiotics and
      several biomarkers of oxidative stress were analysed after 2 and 7 days exposure.
      The levels of soluble thiobarbituric acid reactive substances (TBARS) increased
      markedly in animals treated with polar xenobiotics, CuCl2 or paraquat; exposure
      to the apolar xenobiotics, dieldrin or malathion, enhanced significantly the
      microsomal TBARS while decreasing the microsomal glutathione transferase
      activity. The specific superoxide dismutase (SOD) activity increased in Cu(II)
      injected animals but diminished in fish exposed to paraquat. After
      isoelectrofocusing separation and activity staining cell-free extracts of fish
      exposed to Cu(II), dieldrin or malathion displayed two new Cu,Zn-SOD isoforms of
      intermediate pI. An additional Mn-SOD was observed in dieldrin-injected fish, but
      only a faint new acidic isoform was observed in paraquat-injected animals. The
      new SOD bands were reproduced in vitro by incubation of cell-free extracts with
      systems generating superoxide anion or hydrogen peroxide and with a tert-butyl
      hydroperoxide/ADP-Fe system. Metallothionein induction was observed in Cu(II) or
      paraquat-exposed fish, but not in animals injected with apolar xenobiotics. So,
      the new SOD bands are possibly oxidized forms of this enzyme and can be
      considered as useful early biomarkers of oxidative stress due to transition
      metals or organic xenobiotics.

PMID- 8548865
TI  - Inhibition of 1,2,4-benzenetriol-generated active oxygen species and induction of
      phase II enzymes by green tea polyphenols.
AB  - Autooxidation of polyphenolic metabolites of benzene, such as hydroquinone (HQ),
      catechol (CT), 1,2,4-benzenetriol (BT) and pyrogallol (PG), produced several
      kinds of active oxygen species (AOS). BT and PG induced DNA breaks in the absence
      of metal ions, especially when producing AOS such as H2O2, O2-, HO. or 1 delta
      gO2. HQ and CT did not result in double-strand DNA breaks, except when ferrous
      ion was added, indicating the participation of the Fenton reaction. Polyphenolic
      fractions isolated from green tea (GTP) exerted inhibitory effects on the
      autooxidation of BT and suppressive effects on H2O2 or HO. generated from
      phenolic metabolites of benzene in the presence of S9 or an in vivo system.
      Additionally, although the activities of antioxidant and phase II enzymes were
      elevated by both GTP and phenolic metabolites of benzene, GTP counteracted the
      lowering GSH caused by phenolic metabolites of benzene in rat liver. The above
      results suggest that GTP and phenolic metabolites of benzene are antagonistic in
      their response to AOS, especially hydroxyl radical.

PMID- 8548866
TI  - Integrin mediated signal transduction in oncogenesis: an overview.

PMID- 8548867
TI  - Fibronectin and integrins in invasion and metastasis.
AB  - The adhesive glycoprotein fibronectin and integrin receptors appear to play
      important roles in the progression of metastatic disease. Fibronectin is a
      multifunctional extracellular glycoprotein that has at lest two independent cell
      adhesion regions with different receptor specificities. The cell adhesive region
      in the central portion of fibronectin is comprised of at least two minimal amino
      acid sequences--an Arg-Gly-Asp (RGD) sequence and a Pro-His-Ser-Arg-Asn (PHSRN)
      sequence--which function in synergy. Another cell adhesive region is located near
      the carboxy-terminus in the alternatively spliced IIICS module. The critical
      minimal sequences for this region Leu-Asp-Val (LDV) and Arg-Glu-Asp-Val (REDV)
      which function in an additive rather than synergistic fashion. Integrins are
      heterodimeric, transmembrane cell adhesion receptors for fibronectin and other
      extracellular matrix molecules. Several different integrins bind to fibronectin.
      The alpha 5 beta 1 fibronectin-specific integrin binds to the central RGD/PHSRN
      site. The alpha 4 beta 1 integrin binds to the IIICS site. Fibronectin-integrin
      interactions are important in tumor cell migration, invasion, and metastasis. In
      addition to promoting cell adhesion to the extracellular matrix, these proteins
      may also function in chemotaxis and control of proliferation. Peptide and
      antibody inhibitors of fibronectin and integrin functions have been shown to be
      effective inhibitors of metastasis, and are potentially important reagents for
      the study and control of cancer.

PMID- 8548868
TI  - Involvement of integrins in cell survival.
AB  - Apoptosis is a regulated process of cell death by which cells actively
      participate in their own destruction. In multicellular organisms, the balance
      between cell proliferation and apoptosis provides homeostatic control, and a
      regulatory failure of either event can contribute to oncogenesis. The
      extracellular matrix (ECM) is known to play a regulatory role in cellular growth
      and differentiation, but only more recently has it been recognized as a regulator
      of apoptosis. In these processes the major transmitters of ECM-derived signals to
      the cell are members of the integrin family, although the mechanical process of
      cell spreading also plays a role. Both in vivo and in vitro the loss of adhesion
      to specific components of the ECM can lead to cell death, and such apoptosis can
      be induced experimentally by blocking integrin binding. Heterotypic and homotypic
      cell-cell adhesion can also protect from adhesion-dependent apoptosis and there
      is evidence to suggest that this too in integrin mediated. In addition, some
      integrin mediated signaling appears to promote apoptosis. The downstream
      mechanisms of integrin signaling causing cell death have not been greatly
      explored, but there is evidence from two different systems that the induction of
      ICE transcription and nuclear translocation of p53 are candidate processes.
      Alterations in integrin expression or signaling therefore are likely to
      contribute to tumor development by enabling escape from apoptosis. Also, the
      recognition of the importance of cell-cell adhesion in tumor cell survival offers
      the potential of developing improved drug regimes for the treatment of
      malignancy.

PMID- 8548869
TI  - Growth factor regulation of integrin-mediated cell motility.
AB  - Cell motility, a primary component of tumor cell invasion, is a continuum of
      sequential events in which the cell extends pseudopodia, forms nascent
      attachments, assembles and contracts the cytoskeleton, and finally, as it
      translocates forward, disengages distal adhesions. What triggers cells to move?
      Substratum contact mediated by integrin adhesion receptors is important, but
      other signals such as chemokinetic factors appear to be required for continued
      crawling. It is now apparent that integrins do not simply bind cells to matrix in
      a Velcro-like fashion, but also are potent signaling molecules. Initial
      engagement of integrins induces their condensation into focal contacts, forming
      anchors to the extracellular matrix and discrete signal-transducing complexes on
      the cytoplasmic surface. A number of growth factors, through either autocrine or
      paracrine pathways, can activate the cellular machinery that mobilizes the cell.
      Thus, these two classes of receptors--the integrin receptors that bind specific
      extracellular adhesion molecules, and growth factor receptors that bind their
      respective ligands--can regulate cell locomotion. Not surprisingly, there is
      'cross-talk' between integrin and growth factor receptors that occurs through
      their common intracellular signaling pathways. In this way, each receptor type
      can either amplify or attenuate the other's signal and downstream response. An
      example of growth factor-induced motility is the epithelial-mesenchymal
      transition induced by hepatocyte growth factor/scatter factor (HGF/SF). When
      bound to its receptor, the c-met proto-oncogene product, HGF/SF induces a
      phenotypic conversion that appears to be an important aspect of tumor progression
      in malignant carcinomas. The motogenic response produced by HGF/SF in carcinoma
      cells occurs in discrete steps in which integrins and focal adhesion kinase
      (p125FAK) are first recruited to focal contacts. This is rapidly followed by cell
      spreading, disruption of focal adhesions and cell-cell contacts, and, finally,
      cell crawling. The precise mechanism by which growth factors such as HGF/SF and
      its receptor induce this motogenic response and modulate integrin function has
      not been clearly defined but appears to involve several signaling pathways.
      Understanding the process by which growth factor and integrin receptors interact
      and regulate motility may suggest novel targets for therapeutic intervention.

PMID- 8548870
TI  - The alpha 6 beta 1 and alpha 6 beta 4 integrins in human prostate cancer
      progression.
AB  - Prostatic secretions are formed by glands composed of basal and luminal cells and
      surrounded by a basal lamina. The normal basal cells express several integrins
      (extracellular matrix receptors) including alpha 2, 3, 4, 5, 6, v, beta 1 and
      beta 4. These integrin units are polarized at the base of the cells adjacent to
      the basal lamina. The integrin alpha 6 beta 4 is associated with hemidesmosomal
      like structures. The natural history of prostate cancer involves the presence of
      prostatic intraepithelial neoplasia (PIN) lesions (considered precursor lesions),
      carcinoma in situ and invasive carcinoma. Hemidesmosomal proteins and the alpha 3
      beta 1 and alpha 6 beta 1 integrins (laminin receptors) are retained in the early
      PIN lesions. Expression of the integrins alpha 2, alpha 4, alpha 5, alpha v and
      beta 4 is lost in carcinoma. The alpha 3 beta 1 and alpha 6 beta 1 integrins
      remain associated with invasive carcinoma, the latter being predominant. Integrin
      expression in carcinoma is diffuse in the plasma membrane and not restricted to
      the basal aspects of the cell. The alpha 6 beta 1 integrin is fully functional as
      judged by an ability to adhere to laminin and contains the wild type alpha 6A
      cytoplasmic signaling domain. The alpha 6 beta 1 integrin is a leading candidate
      for conferring the invasive phenotype in prostatic carcinoma. Tumor cells with
      high expression of alpha 6 integrin are more invasive when tested in a SCID mouse
      model system. Following intraperitoneal injection, the human tumor cells invade
      the mouse diaphragm and move through the muscle on the surface of the laminin
      coated muscle cells. Our current working hypothesis is that the production of
      alpha 6 beta 1 and laminin in human tumor cells contributes to the invasive
      phenotype. Invasion could occur on the surfaces of laminin coated structures such
      as the nerves, blood vessels or muscle and account for the known patterns of
      human prostate tumor progression. Blockage of the expression or function of alpha
      6 beta 1 or laminin or preventing the loss of beta 4 would be essential steps in
      confining the carcinoma to the prostate gland where conventional treatment has
      already proven effective.

PMID- 8548871
TI  - Integrin expression in non-small cell carcinoma of the lung.
AB  - Alteration of integrin expression in a number of different malignant diseases has
      been recognized, with a trend of downregulation of collagen-laminin binding
      integrin expression in epithelial tumor types noted. This study evaluated the
      expression of a panel of integrin subunits that included subunits that form
      receptors that bind to collagen and laminin (alpha 2, alpha 3, alpha 6 beta 4)
      and subunits that form receptors that bind to fibronectin and fibrinogen (alpha
      5, alpha V, beta 3, beta 6) in 51 specimens of non-small cell carcinoma (NSCCA)
      of the lung by use of immunohistochemistry. Integrin expression was then
      correlated with histologic type (squamous vs. adenocarcinoma), absence or
      presence of hilar or mediastinal nodal metastasis at resection, and cellular
      differentiation (well or poorly differentiated). In general, downregulation of
      the collagen-laminin binding subunits was noted in tumor cells of the NSCCA
      specimens when compared to the progenitor normal bronchial epithelium. No
      differences were noted in integrin expression between squamous cell and
      adenocarcinoma or between node-positive or node-negative tumors. However,
      downregulation of the integrin subunit alpha 3 was noted to be significantly more
      common in poorly differentiated tumors (p = 0.02) and several of the other
      collagen-laminin binding subunits also appeared to be more downregulated in
      poorly differentiated tumors. No upregulation was seen in the alpha 5 subunit of
      the fibronectin receptor or the beta 3 subunit of the vitronectin receptor,
      however, approximately 50% of tumors showed upregulation of the beta 6 subunit,
      the great majority of these being well-differentiated, node-negative tumors.
      Downregulation of the collagen-laminin integrins may thus be associated with
      differentiation of NSCCA, but not metastasis, and may serve as an adjunctive
      prognostic marker of disease. The beta 6 subunit appears to be associated with
      malignant transformation, but may serve as a positive prognostic factor.

PMID- 8548873
TI  - Targeted cancer chemotherapy with arterial microcapsule chemoembolization: review
      of 1013 patients.
AB  - To evaluate the feasibility of intraarterial infusion of microencapsulated
      anticancer drugs (chemoembolization), collective data on 1013 cancer patients
      were reviewed. Ethylcellulose microcapsules containing mitomycin C (median total
      dose 20 mg), cisplatin (60 mg) or peplomycin (40 mg) were given to tumor-feeding
      arteries by bolus infusion in 79% of the patients and by fractionated infusion in
      the others, as a palliative (71%) or preoperative measure (29%). The target sites
      were the liver (42%), kidney (24%), intrapelvic organs (18%), lung (4%), head and
      neck (3%), bone (1%) and others (9%), excluding the central nervous system and
      gastrointestinal tract. The incidence of overall adverse effects ranged from 0.2
      to 54.9%, but grade 2-3 hematological, renal and hepatic toxicities, local pain,
      abdominal discomfort, cutaneous reaction, remote embolization and infection were
      < 10%. Nine patients (0.9%) in the early stages of trials suffered serious
      complications including treatment-related death in two with critical underlying
      diseases of the target organs. The remaining patients recovered from the adverse
      effects, except for grade 2 cutaneous reactions, within 2 months by routine
      palliative measures. A > or = 50% tumor reduction was seen in 28% of 427
      evaluable tumors (42% for < 25-cm2 tumors and 20% for > or = 25-cm2 tumors) with
      a median treatment number of one. The response rate depended on both the tumor
      size and the treatment number (P < 0.05), but it was not affected by prior
      therapies. Mitomycin C microcapsules produced a higher response rate. Complete or
      partial remission of intractable pain and genitourinary gross hemorrhage was
      found in two-thirds of eligible patients. The results indicate that this
      treatment modality, though restricted by catheter technique, can be applied to
      various tumor lesions with an acceptable morbidity and prospective trials are
      justified to evaluate the potential role of such a targeted chemotherapy.

PMID- 8548872
TI  - The role of the integrin vitronectin receptor, alpha v beta 3 in melanoma
      metastasis.

PMID- 8548874
TI  - Transport mechanism of anthracycline derivatives in human leukemia cell lines:
      uptake and efflux of pirarubicin in HL60 and pirarubicin-resistant HL60 cells.
AB  - We studied the transport mechanism of pirarubicin (THP) in HL60 and its THP
      resistant (HL60/THP) cells, which showed no expression of mdr1 mRNA on Northern
      blot analysis. Under physiological conditions, the uptake of THP by both types of
      cell was time- and temperature-dependent. The amount of drug transport in the
      resistant cells was significantly less than that in the parent cells within 3 min
      of incubation. THP uptake was significantly higher in the presence than in the
      absence of 4 mM 2,4-dinitrophenol (DNP) in glucose-free Hanks' balanced salt
      solution in both HL60 and HL60/THP cells and the increases were approximately
      equal. In the presence of DNP, the uptake of THP by both types of cell was
      concentration-dependent, and there were no significant differences in the
      apparent kinetic constants (Michaelis constant (Km), maximum velocity (Vmax) and
      Vmax/Km) for THP uptake between HL60 and HL60/THP cells. Additionally, THP
      transport was competitively inhibited by its analogue doxorubicin. The efflux of
      THP from HL60/THP cells was significantly greater than that from HL60 cells, and
      the release from both types of cell was completely inhibited by decreasing the
      incubation temperature to 0 degrees C and by treatment with DNP in glucose-free
      medium. In contrast, the P-glycoprotein inhibitors verapamil and cyclosporin A
      did not inhibit THP efflux. However, genistein, which is a specific inhibitor of
      multidrug resistance-associated protein (MRP), increased the THP remaining in the
      resistant cells, and the value was approximately equal to that of the control
      group in the sensitive cells. These results suggest that THP is taken up into
      HL60 and HL60/THP cells via a common carrier by facilitated diffusion, and then
      pumped out in an energy-dependent manner. Furthermore, the accelerated efflux of
      THP by a specific mechanism, probably involving MRP, other than the expression of
      P-glycoprotein, resulted in decreased drug accumulation in the resistant cells,
      and was responsible, at least in part, for the development of resistance in
      HL60/THP cells.

PMID- 8548875
TI  - Development of an orthotopic SCID mouse-human tumor xenograft model displaying
      the multidrug-resistant phenotype.
AB  - Multiple myeloma is a plasma cell malignancy which is generally incurable in
      spite of a high initial response to chemotherapy. While animal models of myeloma
      are known, the recent developments of human xenografts in nude and SCID mice
      suggests a promising experimental model. The SCID model, in particular, holds
      promise because these animals readily accept hematopoietic and lymphoid
      transplantation and do not generally develop graft versus host reaction. We have
      developed two drug-resistant variants of the human multiple myeloma cell line ARH
      77 by in vitro exposure to gradually increasing concentrations of doxorubicin
      (ARH-D60) or mitoxantrone (ARM-80). When injected into irradiated SCID mice, the
      ARH-D60 cell line grew in an orthotopic pattern with the development of
      osteolytic lesions. This is in contrast to the 8226/C1N human myeloma cell line
      which grows in a disseminated but nonorthotopic manner in the SCID mouse. Both
      the ARH-D60 and ARM-80 cell lines are resistant to doxorubicin and cross
      resistant to mitoxantrone, vinca alkaloids, taxol and m-AMSA while maintaining
      sensitivity to antimetabolites and alkylating agents. Growth characteristics and
      cell cycle kinetics, including S-phase, were not altered in the resistant
      sublines. The ARH-D60 and ARM-80 cell lines both displayed a classic multidrug
      resistance (MDR) phenotype which was partially reversed by the addition of
      verapamil. These two cell lines represent the first MDR human myeloma cell lines
      which have demonstrated an orthotopic growth pattern in the SCID mouse and thus
      may be of value in studying the pathophysiology of this disease.

PMID- 8548876
TI  - Difference in CDDP penetration into CSF between selective intraarterial
      chemotherapy in patients with malignant glioma and intravenous or intracarotid
      administration in patients with metastatic brain tumor.
AB  - Platinum (Pt) levels in plasma and cerebrospinal fluid (CSF) in patients with
      malignant glioma were determined after initiation of selective intraarterial
      chemotherapy with a combination of VP-16 (etoposide) and CDDP (cisplatin), and
      were compared with the CSF Pt levels in patients with metastatic brain tumors
      after intravenous or intracarotid administration of VP-16 and CDDP. CSF Pt levels
      were also compared for various administration routes, doses, CSF sampling routes
      and blood-CSF barriers in metastatic brain tumor. Changes in the blood-CSF
      barrier to CDDP during treatment in a patient with meningeal lymphoma and in a
      patient recovering from surgical removal of a metastatic brain tumor were also
      examined by periodic administration of CDDP. All CSF samples were taken through
      Ommaya reserviors placed in the anterior horn of the lateral ventricle or the
      postoperative cavity. The mean peak CSF/plasma total Pt ratio (T/T ratio) and the
      mean CSF total Pt/plasma ultrafiltrable Pt ratio (T/U ratio) were highest (15.0%
      and 24.4%, respectively) following selective intraarterial infusion of CDDP in
      patients with malignant glioma, followed by intravenous infusion in meningeal
      carcinomatosis (11.5% and 18.9%), intracarotid administration (5.4% and 8.7%) and
      intravenous infusion (60 mg/m2 2.5% and 100 mg/m2 2.9%; and 60 mg/m2 3.5% and 100
      mg/m2 7.7%) in patients with the solid type of metastatic brain tumor. In CSF
      obtained from the postoperative cavity in cases of metastatic brain tumor, T/T
      and T/U ratios were extremely high (40.9% and 62.4%). However, the CSF Pt level
      even after selective intraarterial administration of CDDP in malignant glioma was
      0.51-1.64 micrograms/ml total Pt and 0.43-1.08 micrograms/ml ultrafiltrable Pt.
      Even the CSF level obtained from the postoperative cavity was 1.0-4.7
      micrograms/ml total Pt. These low levels of total and ultrafiltrable Pt are
      considered not to be cytotoxic to disseminated cells in the CSF space and to
      normal brain cells. As for changes in the blood-CSF barrier, repeated
      administration of CDDP showed that the rate of entry of Pt into the CSF decreased
      in parallel with improvements apparent on CT scans in the patient with meningeal
      lymphoma, and also showed that the blood-CSF barrier to Pt was gradually repaired
      after the metastatic brain tumor had been removed.

PMID- 8548877
TI  - Bioavailability of 50- and 75-mg oral etoposide in lung cancer patients.
AB  - This study was designed to determine the bioavailability of etoposide capsules
      administered orally at doses of 50 and 75 mg. Patients with inoperable or
      relapsed lung cancer, who had an Eastern Cooperative Oncology Group (ECOG)
      performance status of 0-2 and adequate organ function, were eligible. A group of
      17 patients were evaluable, all of whom were 75 years old or less, with an ECOG
      performance status of 0 or 1. The bioavailability of oral etoposide was
      determined by measuring the area under the etoposide plasma concentration versus
      time curve (AUC) on days 1, 10 and 21 during a once-daily regimen of oral
      administration for 21 consecutive days and comparing the value with the AUC
      achieved following intravenous administration 1 or 2 weeks after the last oral
      dose. The bioavailability of 50, 75 and 100 mg oral etoposide was determined in
      six, nine and two patients, respectively. The mean etoposide bioavailabilities
      (+/- SD) of the 50-mg and 75-mg doses were 47 +/- 11% and 59 +/- 18%,
      respectively, and of the 100-mg dose in two patients were 51% and 33%,
      respectively. There was no statistically significant difference in
      bioavailability between the 50-mg and 75-mg doses. The bioavailability of low
      dose oral etoposide was the same as that reported in previous higher dose oral
      etoposide bioavailability studies and that shown on the package insert supplied
      by the manufacturer. Improved bioavailability of low-dose oral etoposide was
      therefore not observed in a population of Japanese patients.

PMID- 8548878
TI  - The N-dechloroethylation of ifosfamide: using stereochemistry to obtain an
      accurate picture of a clinically relevant metabolic pathway.
AB  - The cumulative urinary excretions of the enantiomers of ifosfamide [(R)-IFF, (S)
      IFF)] and their 2-N-dechlorethylated (2-DCE-IFF) and 3-N-dechloroethylated (3-DCE
      IFF) metabolites were determined in 11 adult cancer patients who received a
      single 3-h infusion of IFF (3 g/m2) with mesna uroprotection. The urine samples
      were analyzed for the compounds of interest using an enantioselective gas
      chromatographic-mass spectrometric assay. The results indicated an
      enantioselective excretion of the parent and N-dechloroethylated metabolites: the
      urinary recovery of (R)-IFF was significantly greater than that of (S)-IFF (1.73
      +/- 0.45 vs 1.43 +/- 0.41 mmol, P < 0.0001); the excretion of (S)-2-DCE-IFF (0.75
      +/- 0.53 mmol) was greater than that of (R)-2-DCE-IFF (0.42 +/- 0.22 mmol, P =
      0.071) while the excretion of (R)-3-DCE-IFF (1.64 +/- 0.76 mmol) was greater than
      that of (S)-3-DCE-IFF (0.77 +/- 0.59 mmol, P = 0.012). The study also revealed
      two distinct metabolic patterns in which the urinary recoveries of (R)-2-DCE-IFF
      and (R)-3-DCE-IFF were linked as were those of (S)-2-DCE-IFF and (S)-3-DCE-IFF.
      The results suggest that at least two enzymes are involved in the N
      dechlorethylation of IFF. The data also demonstrate the importance of following
      the metabolic fate of (R)-IFF and (S)-IFF and of determining the relative urinary
      excretion of all dechloroethylated metabolites.

PMID- 8548879
TI  - Investigations on the mechanisms of methotrexate resistance in a cisplatin
      resistant L1210 murine leukemia cell subline.
AB  - We report a murine leukemia cell variant (L1210/DDP), selected for cisplatin
      (DDP) resistance, to be cross-resistant to methotrexate (MTX). Cross-resistance
      of L1210 cells to DDP and MTX has been observed by others, and has also been
      recorded in P388 murine leukemia and SSC-25 human squamous carcinoma cells. We
      demonstrated that MTX resistance is not due to dihydrofolate reductase (DHFR)
      gene amplification, increased DHFR enzyme activity or decreased MTX binding to
      the target enzyme. Of the mechanisms commonly proposed for MTX resistance, only
      differences in transport were observed when comparing sensitive (L1210/0) and
      resistant (L1210/DDP) cells. Our results suggest that MTX resistance in L1210/DDP
      cells is due to altered methotrexate uptake.

PMID- 8548880
TI  - Hypocrellins as photosensitizers for photodynamic therapy: a screening evaluation
      and pharmacokinetic study.
AB  - Hypocrellin compounds were selected as potential photosensitizers for
      photodynamic therapy (PDT) owing to their high quantum yields of singlet oxygen
      (1O2), and facility for site-directed chemical modification to enhance
      phototoxicity, pharmacokinetics, solubility, and light absorption in the red
      spectral region, among other properties. Parent hypocrellins A and B share an
      absorption peak at 658 nm. These molecules may therefore be considered useful
      progenitors of derivatives which absorb more strongly in the red, considering
      that the ideal sensitizer should absorb in the 650-800 nm range, beyond the
      absorption range of hemoglobin and melanin, and where light penetration in
      tissues is maximized through reduced scattering. A series of pure, monomeric
      hypocrellin derivatives was tested for properties of dark cytotoxicity and
      photosensitizing potential by clonogenic assay in monolayer cultures of EMT6/Ed
      murine tumor cells. Their respective toxicities are reported on a molar basis.
      The in vitro screening assay has, to date, resulted in the selection of four
      hypocrellin derivatives for further development as photosensitizers for PDT.
      Cellular uptake for photosensitizing doses of selected compounds was determined
      by fluorimetry. Dose escalation studies in rodents indicate that potentially
      photosensitizing doses promote no demonstrable systemic toxicity.

PMID- 8548881
TI  - Vincristine-induced dermal toxicity is significantly reduced when the drug is
      given in liposomes.
AB  - A problem associated with the intravenous delivery of vincristine concerns drug
      extravasation at the site of injection or infusion. This can result in extensive
      local soft-tissue damage. A new formulation of vincristine has recently been
      developed based on encapsulation of the drug in liposomes. The liposomal drug is
      somewhat less toxic and substantially more efficacious than free drug. The
      studies described here assessed, using a murine model of drug extravasation,
      whether vincristine encapsulation in liposomes influences drug-induced dermal
      toxicity. It was shown that subcutaneous injection of vincristine in liposomes
      does not result in the gross skin necrosis and ulceration observed following
      injection of free drug. Histological analysis of the dermal tissue surrounding
      the injection site suggests that free drug induces a pronounced inflammatory
      reaction as judged by the presence of infiltrating leukocytes. In contrast, the
      liposomal formulation of vincristine engenders a mild prolonged inflammatory
      condition. These toxicological studies were correlated with an evaluation of drug
      retention at the site of administration. It was shown using radiolabelled
      vincristine as a drug marker, that free vincristine is rapidly eliminated from
      the injection site. In contrast, the level of drug at the site of injection was
      far greater when the drug was given in liposomal form.

PMID- 8548882
TI  - A comparison of methods for limited-sampling strategy design using data from a
      phase I trial of the anthrapyrazole DuP-941.
AB  - The pharmacokinetics of a drug in individual patients can be estimated using
      plasma samples collected at a limited number of time points. However, different
      methods for a limited-sampling strategy (LSS) design exist and the optimal method
      has not yet been defined. Plasma concentration data were available from 27 of 74
      courses in a phase I study (dose range, 5-55 mg m-2) of the novel anthrapyrazole
      DuP-941. Three approaches to LSS development were compared. Firstly, forward
      stepwise regression (FSR) was used to derive equations to predict the DuP-941
      area under the concentration-time curve (AUC) based on plasma concentrations
      measured at specified times. LSSs were developed using 14 randomly chosen data
      sets and were validated using the remaining 13 data sets. Secondly, "all subsets"
      regression (ASR) was used to develop LSSs. A jack-knife technique was also used
      to allow model development utilising 26 data sets and validation on the 27th data
      set. Thirdly, an LSS was developed using optimal sampling theory (OST), and the
      LSS was used in conjunction with a Bavesian algorithm. Selected sampling times
      for four-point LSSs were 10, 65, 185 and 485 min (FSR) and 10, 45, 200 and 480
      min (OST). Ten candidate LSSs were developed using the ASR approach. ASR- and
      OST/Bayesian-derived four-point LSSs gave more precise (P < 0.05) estimates of
      AUC [mean absolute percentage of difference (MAD%) +/- SD: ASR, 6.4 +/- 3.7%;
      OST/Bayesian, 6.8 +/- 4.6%] than did FSR (MAD% = 15.1 +/- 9.9%). The OST/Bayesian
      approach is recommended because it allows estimation of all model parameters and
      is more flexible with regard to sample collection time and design variables.

PMID- 8548883
TI  - Isozyme-specific glutathione S-transferase inhibitors potentiate drug sensitivity
      in cultured human tumor cell lines.
AB  - Novel glutathione (GSH) analogs, previously shown to inhibit glutathione S
      transferase (GST) activity at about 1 microM in vitro, were tested for their
      ability to potentiate the killing of cultured tumor cells by chemotherapeutic
      drugs. When tested at doses up to 200 microM, the analogs were neither toxic nor
      capable of potentiating drug toxicity unless the diethyl ester (DEE) form was
      used for treatment of the cells. HPLC analysis revealed rapid internalization of
      the DEE and intracellular conversion to a monoethyl ester form that accumulated
      in the cell, followed by a more gradual loss of the second ester to generate the
      active parent form. For the four GSH analogs tested, the ability of the DEE forms
      to potentiate chlorambucil (CMB) toxicity in HT-29 human colon adenocarcinoma
      cells strongly correlated with the in vitro ability of the parent form to inhibit
      recombinant human P1-1. This isozyme is the dominant form of GST present in HT-29
      cells. Of the four analog DEEs tested, gamma-glutamyl-S-(benzyl)cysteinyl-R(-)
      phenyl glycine (TER 117) DEE was the most effective in potentiating CMB toxicity
      in several cell lines: HT-29, HT4-1 (HT-29 subclone), SKOV-3 ovarian carcinoma,
      and SK VLB (vinblastine-resistant variant of SKOV-3) cells. gamma-Glutamyl-S
      (octyl)cysteinyl-glycine (TER 143) DEE potentiated mitomycin C (MTC) toxicity in
      HT4-1 and SK VLB cells while TER 117 DEE did not. TER 117 DEE enhanced melphalan
      effects on xenografts of HT4-1 in mice to a similar extent as that achieved with
      the previously described nonspecific GST inhibitor, ethacrynic acid. Taken
      together, our results indicate that cell-permeable analogs of GSH can potentiate
      cytotoxicity of common chemotherapeutic drugs and this effect has a strong
      positive correlation with the ability of the analogs to inhibit specific GST
      isozymes.

PMID- 8548884
TI  - Pharmacokinetics and antitumor effects of mitoxantrone after intratumoral or
      intraarterial hepatic administration in rabbits.
AB  - The intratumoral (i.t.) delivery of anticancer drugs aims at controlling tumor
      growth and thereby provides palliative treatment for liver neoplasms.
      Mitoxantrone is a good candidate for local or regional administration because (1)
      its metabolism is mainly hepatic, (2) it has a steep dose-response curve for
      multiple solid tumors, and (3) its fixation in tissues is sustained without
      vesicant effects after extravasation. We compared the tolerance,
      pharmacokinetics, and antitumor effects of mitoxantrone on hepatic VX2 tumors in
      rabbits treated with i.t. intraarterial hepatic (i.a.h.) or i.v. mitoxantrone,
      i.t. ethanol; or i.t. 0.9% NaCl and in control animals. Tumor growth rates (TGRs)
      were evaluated at 9 days after treatment. Myelosuppression was the limiting
      toxicity of i.v. mitoxantrone at 1.5 mg/kg (maximal tolerated dose, MTD), but
      neither i.t. nor i.a.h. administration led to hematologic toxicity at the same
      dose. The mitoxantrone retained in tumors after i.t. administration was seen as
      blue-stained areas of complete necrosis according to histologic analysis.
      Pharmacokinetic parameters showed a significantly decreased systemic exposure to
      the drug after both regional treatments, although the i.a.h. route appeared to
      have an edge over the i.t. route. TGRs were significantly reduced after i.t.
      mitoxantrone (81 +/- 62%), i.a.h. mitoxantrone (337 +/- 110%), and i.t. ethanol
      treatments (287 +/- 117%) as compared with control values (886 +/- 223%; p <
      0.01). Treatment with i.v. mitoxantrone (816 +/- 132%) had no antitumor effect,
      nor did NaCl injections (868 +/- 116%). Mitoxantrone given i.t. induced the
      highest antitumor effects, resulting in a 3.5-fold reduction in TGRs as compared
      with i.a.h. mitoxantrone and i.t. ethanol treatments (p < 0.02). Treatment with
      i.t. mitoxantrone provided efficient antitumor therapy without producing major
      side effects. This method should be considered as palliative treatment for
      nonresectable liver tumors and other localized malignancies.

PMID- 8548885
TI  - Phase II study of second-line treatment with high-dose cyclophosphamide in
      recurrent metastatic breast cancer.
AB  - A total of 78 patients with second recurrence or progression of histologically
      verified breast cancer were treated with single-agent cyclophosphamide given at
      2.5 g/m2 by i.v. infusion every 3 weeks along with mesna support. All had
      previously been treated with epirubicin and cisplatin or epirubicin alone.
      Toxicity was predominantly hematologic: WHO grade III+IV toxicity was found in
      95% of cases. The overall response rate was 26.7% (95% confidence limits, 15.8
      41.4%), with 7% of patients achieving a complete response (CR) and 19.7%, a
      partial response (PR). The median duration of CRs and PRs was 11 and 5 moths,
      respectively. The response rate observed for patients previously treated with
      epirubicin alone was 30.5% in contrast to the 8.3% recorded for patients
      previously treated with cisplatin plus epirubicin. Thus, an indication of cross
      resistance was absent between cyclophosphamide and epirubicin but possible
      between cyclophosphamide and cisplatin.

PMID- 8548886
TI  - Docetaxel and paclitaxel inhibit DNA-adduct formation and intracellular
      accumulation of cisplatin in human leukocytes.
AB  - The purpose of this study was to determine the mechanism of the pharmacodynamic
      interaction between docetaxel/paclitaxel and cisplatin. Cisplatin-induced DNA
      adducts and cisplatin accumulation were quantitated in peripheral blood
      leukocytes (WBC). The WBC were obtained from patients treated with docetaxel or
      paclitaxel in phase I/II studies and were incubated in vitro with cisplatin. In
      addition, blank whole-blood samples were obtained from patients and healthy
      subjects and incubated in intro with cisplatin or docetaxel/paclitaxel and
      cisplatin. The cisplatin-induced DNA-adduct levels measured in WBC after
      treatment with docetaxel or paclitaxel were significantly lower than those
      determined in non-pretreated WBC. Docetaxel and paclitaxel reduced the
      intracellular accumulation of cisplatin in WBC by 46-47%. If the pharmacodynamic
      interaction between docetaxel/paclitaxel and cisplatin also occurs in other
      normal tissues such as bone marrow, it may well contribute to the sequence
      dependent toxicity that has been observed in clinical studies.

PMID- 8548887
TI  - Medicare reform addresses managed care issues.

PMID- 8548888
TI  - The search for a better exercise test. A self-fulfilling prophecy?

PMID- 8548889
TI  - Cell-free hemoglobin as an oxygen carrier removes nitric oxide, resulting in
      defective thromboregulation.

PMID- 8548890
TI  - Physical training improves endothelial function in patients with chronic heart
      failure.
AB  - BACKGROUND: Chronic heart failure is associated with endothelial dysfunction
      including impaired endothelium-mediated, flow-dependent dilation (FDD). Since
      endothelial function is thought to play an important role in coordinating tissue
      perfusion and modulating arterial compliance, interventions to improve
      endothelial dysfunction are imperative. METHODS AND RESULTS: To assess the
      potential of physical training to restore FDD, 12 patients with chronic heart
      failure were studied and compared with FDD of 7 age-matched normal subjects. With
      a recently developed high-resolution ultrasound system, diameters of radial
      artery were measured at rest, during reactive hyperemia (with increased flow
      causing endothelium-mediated dilation), and during sodium nitroprusside, causing
      endothelium-independent dilation. Determination of FDD was repeated after intra
      arterial infusion of NG-monomethyl-L-arginine (L-NMMA, 7 mumol/min) to inhibit
      endothelial synthesis and release of nitric oxide. The protocol was performed at
      baseline, after 4 weeks of daily handgrip training, and 6 weeks after cessation
      of the training program. FDD was impaired in heart failure patients compared with
      normal subjects. L-NMMA attenuated FDD, indicating that the endothelial release
      of nitric oxide is involved in FDD. Physical training restored FDD in patients
      with heart failure. In particular, the portion of FDD inhibited by L-NMMA
      (representing FDD mediated by nitric oxide) was significantly higher after
      physical training (8-minute occlusion: 8.0 +/- 1% versus 5.4 +/- 0.9%; P < .05;
      normal subjects: 9.2 +/- 1%). CONCLUSIONS: These results indicate that physical
      training restores FDD in patients with chronic heart failure, possibly by
      enhanced endothelial release of nitric oxide.

PMID- 8548891
TI  - A randomized comparison of combined ticlopidine and aspirin therapy versus
      aspirin therapy alone after successful intravascular ultrasound-guided stent
      implantation.
AB  - BACKGROUND: Previous studies have shown that it is feasible to withhold
      anticoagulation after a successful intracoronary stent procedure with a low
      incidence of stent thrombosis. The importance of specific antiplatelet agents
      when stenting is performed without anticoagulation is unknown. METHODS AND
      RESULTS: After successful intravascular ultrasound-guided stenting, 226 patients
      were randomly assigned to receive either aspirin therapy alone (n = 103) or a
      combination of ticlopidine and short-term aspirin therapy (n = 123). Primary
      angiographic and clinical end points were stent thrombosis, death, myocardial
      infarction, the need for postprocedure coronary artery bypass surgery or repeated
      angioplasty, and significant medication side effects requiring termination of the
      medication within the first month of a successful procedure. At 1 month, the rate
      of stent thrombosis was 2.9% in the aspirin only group and 0.8% in the
      ticlopidine-aspirin group (P = .2). Cumulative major clinical events after
      successful stenting occurred in 3.9% of the patients in the aspirin group and in
      0.8% in the ticlopidine-aspirin group (P = .1). There were no medication side
      effects in the aspirin group; in the combined ticlopidine-aspirin group,
      medication side effects occurred in 3 patients (P = .2). CONCLUSIONS: At 1 month,
      there was no difference in the incidence of stent thrombosis or other clinical
      end points between the two poststent antiplatelet regimens. However, the
      relatively small size of the study and the low incidence of thrombosis events may
      have contributed to the failure to detect differences in angiographic and
      clinical end points between the two groups.

PMID- 8548892
TI  - Clinical implications of the 'no reflow' phenomenon. A predictor of complications
      and left ventricular remodeling in reperfused anterior wall myocardial
      infarction.
AB  - BACKGROUND: Recent studies demonstrated that the "no reflow" phenomenon after
      coronary reflow implies the presence of advanced myocardial damage. In this
      study, we verified the prognostic value of the detection of this phenomenon by
      studying complications, left ventricular morphology, and in-hospital survival
      after acute myocardial infarction (AMI). METHODS AND RESULTS: The study
      population consisted of 126 patients with a first anterior AMI. All patients
      received coronary reflow within 24 hours of onset of symptoms and underwent
      myocardial contrast echocardiography (MCE) before and shortly after coronary
      reflow with an intracoronary injection of sonicated microbubbles. From contrast
      reperfusion patterns, patients were divided into two subsets: those with MCE no
      reflow (47 patients, 37%) and those with MCE reflow (79 patients). There was no
      difference in the frequency of arrhythmia or coronary events between the two
      subsets. Pericardial effusion and early congestive heart failure were observed
      more frequently in patients with MCE no reflow than in those with MCE reflow (26%
      versus 4%, P < .05; 45% versus 15%, P < .05, respectively). Congestive heart
      failure tended to be prolonged in those with MCE no reflow, and 3 patients (7%)
      of this subset died of pump failure. Left ventricular end-diastolic volume
      progressively increased in the convalescent stage in patients with MCE no reflow
      (early versus late, 145 +/- 43 versus 169 +/- 60 mL, P < .001), whereas it
      decreased in those with MCE reflow (154 +/- 42 versus 144 +/- 44 mL, P < .01).
      CONCLUSIONS: The substantial size of the MCE no reflow phenomenon at coronary
      reflow conveys useful information about an outcome of coronary intervention and
      left ventricular remodeling in individual patients with anterior wall AMI,
      although these are suggestive results in a limited number of patients.

PMID- 8548893
TI  - Platelet function in acute myocardial infarction treated with direct angioplasty.
AB  - BACKGROUND: In acute myocardial infarction (AMI), platelets play a key role in
      thrombotic processes that limit the patency of the recanalized, infarct-related
      coronary artery and contribute to reperfusion injury. Platelet function in the
      course of AMI treated by direct percutaneous transluminal coronary angioplasty
      (PTCA) has not been evaluated. METHODS AND RESULTS: In 15 patients with anterior
      AMI, peripheral venous blood samples were obtained before and 4, 8, 24, and 48
      hours after recanalization of the occluded artery by PTCA. Fifteen patients who
      had stable coronary heart disease and were undergoing elective balloon
      angioplasty served as control subjects. Fibrinogen receptor function and surface
      expression of P-selectin on platelets were determined by flow cytometry. In
      addition, we evaluated generation of platelet-derived microparticles and the
      effect of systemic plasma from patients with AMI on normal platelet function and
      on platelet adhesion to human endothelial cells in culture. We found fibrinogen
      receptor activity and P-selectin expression on circulating platelets 8 hours
      after direct PTCA are decreased (P < .01). This coincided with a decrease in
      peripheral platelet count (P < .05) and an increase in generation of
      microparticles (P < .002). Twenty-four to 48 hours after PTCA, fibrinogen
      receptor activity and P-selectin expression increased again. Systemic plasma
      obtained before and after direct PTCA sensitized normal platelets to
      hyperaggregate in vitro (P < .001) and stimulated platelet adhesion to
      endothelial cells in culture (P < .01). None of the changes found in AMI were
      detectable in the control group. CONCLUSIONS: After transient apparent
      deactivation of circulating platelet, probably caused by sequestration of
      hyperactive platelets, the level of platelet activation increases in patients
      with AMI treated by direct PTCA. These findings underscore the need for novel
      antiplatelet strategies in AMI.

PMID- 8548894
TI  - Myocardial rubidium-82 tissue kinetics assessed by dynamic positron emission
      tomography as a marker of myocardial cell membrane integrity and viability.
AB  - BACKGROUND: Recent reports have demonstrated the clinical use of rubidium-82
      chloride (Rb-82) in combination with positron emission tomography (PET) not only
      as a tracer of myocardial blood flow but also as a marker of cell membrane
      integrity using static imaging early and late after tracer injection. The purpose
      of this study was to compare myocardial Rb-82 kinetics assessed by dynamic PET
      imaging as a marker for tissue viability with regional fluorine-18
      fluorodeoxyglucose (FDG) uptake in patients with coronary artery disease. METHODS
      AND RESULTS: Twenty-seven patients with angiographically proven coronary artery
      disease and 5 subjects with a low likelihood for coronary artery disease
      underwent dynamic PET imaging under resting conditions using Rb-82 and FDG. Both
      image sequences served as input data for a semiautomated regional analysis
      program. This program generated polar maps representing Rb-82 tissue half-life
      and FDG utilization assessed by Patlak's approach. Myocardial tissue viability
      was visually determined from static Rb-82 and FDG images. Regions were
      categorized as normal, ischemically compromised, and scar tissue. Their
      coordinates were subsequently copied to the functional polar maps for further
      analyses. In normal subjects, Rb-82 tissue half-life was homogeneous throughout
      the left ventricle (90 +/- 11 seconds). In coronary patients, differences between
      Rb-82 tissue half-lives in normal and scar tissue were highly significant (95 +/-
      10 and 57 +/- 15 seconds, respectively; P < .0001). FDG uptake in these two
      tissue groups was 78 +/- 12% and 40 +/- 13%, respectively (P < .0001).
      Ischemically compromised tissue with reduced perfusion but maintained FDG uptake
      displayed an Rb-82 half-life of 75 +/- 9 seconds, indicating active cellular
      tracer retention, which was significantly different from scar tissue. Overall
      agreement of tissue categorization as either viable or scar was 86% between Rb-82
      kinetics and FDG utilization. In a subgroup of 11 patients with all three tissue
      types within one image set, Rb-82 tissue half-life discriminated between normal,
      ischemic, and scar tissue (97 +/- 9, 75 +/- 9, and 60 +/- 15 seconds,
      respectively; P < .01). CONCLUSIONS: This study demonstrated a significant
      relationship between cell membrane integrity as assessed by dynamic Rb-82 PET
      imaging and myocardial glucose utilization as a marker for tissue viability. In
      regions with reduced perfusion, Rb-82 kinetics was different in compromised but
      metabolically active and irreversibly injured myocardium. The predictive value of
      this approach must be evaluated in follow-up studies.

PMID- 8548895
TI  - Maximal blood lactate level acts as a major discriminant variable in exercise
      testing for coronary artery disease detection in men.
AB  - BACKGROUND: The interpretation of exercise stress testing for coronary artery
      disease detection is affected by the many differences in chosen variables and
      mathematical methods. We conducted a prospective trial to evaluate a global
      muscle fatigue parameter--the blood lactate level achieved at maximal exercise-
      as a method of distinguishing between diseased and nondiseased coronary status.
      METHODS AND RESULTS: We evaluated 236 consecutive male patients without previous
      myocardial infarction who had been referred for the diagnosis of coronary artery
      disease. None of the patients had cardiomyopathy, severe cardiac heart failure,
      or valvular heart disease. Blood lactate concentration at maximal exercise was
      measured as well as other classic variables. Correlations between variables and
      coronary status as assessed by coronary arteriography were described using
      receiver operating characteristic (ROC) curves and logistic regression analysis.
      The first four most powerful variables (lactate level, maximal power output,
      exercise duration, and percentage of maximal predicted heart rate), which are
      directly representative of the global functional capacity, showed values of
      0.777, 0.775, 0.760, and 0.740, respectively, by ROC curve analysis. Mean +/- SD
      blood lactate level at peak exercise reached 7.68 +/- 2.70 mmol/L in the 153
      diseased and 10.56 +/- 2.75 mmol/L in the 83 nondiseased patients (P < .0001).
      After adjustment for other variables, blood lactate level remained a significant
      predictor of coronary artery disease by logistic regression analysis (adjusted
      odds ratio, 1.2; confidence interval, 1.04 to 1.4). CONCLUSIONS: Global muscle
      fatigue as assessed by lactate levels in the blood at maximal exercise appears to
      be a powerful distinguisher of diseased and nondiseased coronary status.

PMID- 8548896
TI  - Coronary thrombi increase PTCA risk. Angioscopy as a clinical tool.
AB  - BACKGROUND: The presence of angiographically identified intracoronary thrombus
      has been variably associated with complications after coronary angioplasty.
      Angiography has been shown to be less sensitive than angioscopy for detecting
      subtle details of intracoronary morphology, such as intracoronary thrombi. The
      clinical importance of thrombi detectable by angioscopy but not by angiography is
      not known. METHODS AND RESULTS: Percutaneous coronary angioscopy was performed in
      122 patients undergoing conventional coronary balloon angioplasty (PTCA) at six
      medical centers. Unstable angina was present in 95 patients (78%) and stable
      angina in 27 (22%). Therapy was not guided by angioscopic findings, and no
      patient received thrombolytic therapy as an adjunct to angioplasty. Coronary
      thrombi were identified in 74 target lesions (61%) by angioscopy versus only 24
      (20%) by angiography. A major in-hospital complication (death, myocardial
      infarction, or emergency bypass surgery) occurred in 10 of 74 patients (14%) with
      angioscopic intracoronary thrombus, compared with only 1 of 48 patients (2%)
      without thrombi (P = .03). In-hospital recurrent ischemia (recurrent angina,
      repeat PTCA, or abrupt occlusion) occurred in 19 of 74 patients (26%) with
      angioscopic intracoronary thrombi versus only 5 of 48 (10%) without thrombi (P =
      .03). Relative risk analysis demonstrated that angioscopic thrombus was strongly
      associated with adverse outcomes (either a major complication or a recurrent
      ischemic event) after PTCA (relative risk, 3.11; 95% CI, 1.28 to 7.60; P = .01)
      and that angiographic thrombi were not associated with these complications
      (relative risk, 0.85; 95% CI, 0.36 to 2.00; P = .91). CONCLUSIONS: The presence
      of intracoronary thrombus associated with coronary stenoses is significantly
      underestimated by angiography. Angioscopic intracoronary thrombi, the majority of
      which were not detected by angiography, are associated with an increased
      incidence of adverse outcomes after coronary angioplasty.

PMID- 8548897
TI  - Midwall left ventricular mechanics. An independent predictor of cardiovascular
      risk in arterial hypertension.
AB  - BACKGROUND: An appreciable proportion of asymptomatic hypertensive patients have
      depressed left ventricular (LV) performance that is identified by midwall
      shortening/endsystolic stress relations but not by indexes that use endocardial
      shortening. It has not been established, however, whether depressed midwall
      ventricular performance has prognostic implications. METHODS AND RESULTS:
      Echocardiographic endocardial and midwall LV fractional
      shortening/circumferential end-systolic stress relations in 294 hypertensive
      patients were analyzed as predictors of the occurrence of cardiovascular morbid
      events that occurred in 50 patients (including 14 deaths) during a 10-year mean
      follow-up. Patients with initially lower midwall but not endocardial shortening,
      either in absolute terms or as a percentage of predicted from observed end
      systolic stress, were more likely to suffer morbid events than those with
      initially normal values (P < .004). Cardiovascular events occurred in 29 of 100
      patients (29%) and death in 10 of 100 patients (10%) among those who were in both
      the two highest quartiles of LV mass index and the two lowest quartiles of
      midwall shortening, as opposed to 21 of 194 (11%) and 4 of 194 (2.1%) of the
      remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3; P < .0001; and odds
      ratio, 5.3; 95% CI, 1.6 to 17.3; P < .006, respectively). In logistic analysis,
      increasing age, high LV mass, high systolic blood pressure, and low values for an
      interaction term between LV mass index and midwall shortening independently
      predicted cardiovascular events (.04 < P < .001); increasing age, low midwall LV
      shortening as a percentage of predicted, and high value of the interaction term
      predicted the occurrence of cardiac death (.004 < P < .0002). Survival analysis
      controlling for age confirmed that low midwall shortening independently predicted
      cardiac morbidity or death, especially in the subgroup of patients with LV
      hypertrophy. CONCLUSIONS: Depressed midwall shortening is a predictor of adverse
      outcome in arterial hypertension; the combination of higher LV mass and lower
      midwall shortening identifies individuals at markedly increased risk.

PMID- 8548898
TI  - Role of nitric oxide in the local regulation of pulmonary vascular resistance in
      humans.
AB  - BACKGROUND: Endothelium-derived nitric oxide (NO) may be an important mediator of
      vascular resistance in the pulmonary circulation. We tested the hypotheses that
      in conscious adults the endothelium, through NO production, is important in
      maintaining basal pulmonary vascular resistance and that it can increase NO
      production further in response to receptor-mediated stimulation, leading to
      further vasodilation. METHODS AND RESULTS: Pulmonary arterial resistance vessel
      function was studied within the distribution of a segmental lower lobe pulmonary
      artery in eight conscious adults 37 to 76 years old who were undergoing cardiac
      catheterization. Segmental blood flow was determined with use of a Doppler-tip
      guide wire and quantitative angiography. Drugs were administered locally within
      the segmental artery through an infusion catheter. NG-Monomethyl-L-arginine (L
      NMMA) was used as a specific inhibitor of NO production, whereas acetylcholine
      (ACh) was used to test receptor-mediated vasodilation. To demonstrate that
      vasodilation to ACh was NO dependent, ACh response was tested alone, in the
      presence of L-NMMA, and in the presence of a control constrictor phenylephrine.
      Basal pulmonary vascular resistance was NO dependent because L-NMMA infusion
      resulted in a dose-dependent decrease in local flow velocity (P < .005), with
      flow decreasing 33% at the highest dose of L-NMMA. ACh infusion resulted in a
      dose-dependent increase in flow velocity (P = .001). The ACh response was at
      least in part NO dependent because it was diminished by the presence of L-NMMA (P
      < .05). The effect of L-NMMA on the ACh response was not due to nonspecific
      preconstriction because L-NMMA diminished the ACh response significantly more
      than did the endothelium-independent constrictor phenylephrine (P < .05) despite
      comparable preconstriction. CONCLUSIONS: In healthy conscious adults, (1) normal
      basal pulmonary resistance is maintained in part by continuous local production
      of NO and (2) the local NO production is responsive to receptor-mediated
      stimulation, leading to further vasodilation, and can be tested with ACh.

PMID- 8548899
TI  - Air travel and adults with cyanotic congenital heart disease.
AB  - BACKGROUND: Concern has been expressed that a reduction of partial oxygen
      pressure during flight in commercial aircraft may induce dangerous hypoxemia in
      patients with cyanotic congenital heart disease. METHODS AND RESULTS: To evaluate
      the validity of this concern, the transcutaneous SaO2 was measured in 12 adults
      with this type of heart disease and 27 control subjects during simulated
      commercial flights of 1.5 and 7 hours in a hypobaric chamber. Ten of those
      patients and 6 control subjects also were evaluated during two actual flights of
      approximately 2.5 hours in a DC-10 and an A-310, respectively. During the
      prolonged simulated and actual flights, the capillary blood pH, gases, and lactic
      acid were analyzed in the patients and during one of the actual flights also in
      the control subjects. During the simulated flights the SaO2 was at all times
      lower in the patients than in the control subjects. However, the maximal mean
      actual percentage decrease, as compared with sea level values, did not exceed
      8.8% in either patients or control subjects. During the actual flights, this
      maximal decrease in the patients was 6%. In-flight reduction of the capillary PO2
      was considerable in the control subjects but not in the patients. It is our
      hypothesis that the lack of a significant decrease of the PO2 in the patients
      might possibly be due to a high concentration of 2.3 diphosphoglycerate in the
      red cells. The flights had no influence on the capillary blood pH, PCO2,
      bicarbonate, or lactic acid levels in either patients or control subjects.
      CONCLUSIONS: Atmospheric pressure changes during commercial air travel do not
      appear to be detrimental to patients with cyanotic congenital heart disease.

PMID- 8548900
TI  - Effect of slow pathway ablation on ventricular rate during atrial fibrillation.
      Dependence on electrophysiological properties of the fast pathway.
AB  - BACKGROUND: Catheter ablation of the posteroseptal right atrium has been proposed
      for control of ventricular rate in patients with tachycardic atrial fibrillation
      (AF). However, the exact mechanism of rate control is unclear. Because the
      ablation site corresponds to the location of the slow pathway in patients with AV
      nodal reentry tachycardia (AVNRT), we investigated whether selective ablation of
      this posterior AV nodal input can provide a sufficient reduction in heart rate
      during AF. METHODS AND RESULTS: In 30 patients with AVNRT, conduction properties
      of the AV nodal pathways were determined before and after slow pathway ablation.
      AF was induced by burst pacing at baseline and after ablation, and the mean
      ventricular cycle length was determined. After slow pathway ablation, the mean
      ventricular cycle length during AF increased (449 +/- 98 versus 515 +/- 129
      milliseconds, P < .01). At baseline, the mean ventricular cycle length correlated
      with the Wenckebach cycle length of both the slow (r = .90) and fast (r = .86)
      pathways. After ablation, the mean ventricular cycle length was extremely well
      determined by the Wenckebach cycle length of the fast pathway (r = .94). However,
      the slope of the regression line was significantly steeper compared with baseline
      (1.50 versus 0.77, P < .0001), illustrating that the reduction in ventricular
      rate was not as evident if the fast pathway had a short Wenckebach cycle length.
      CONCLUSIONS: Selective elimination of the slow pathway reduces ventricular rate
      during AF. However, in patients with a short Wenckebach cycle length of the
      anterior AV nodal input that causes tachycardic AF, this effect may be
      insufficient to provide adequate control of ventricular rate.

PMID- 8548901
TI  - Electrophysiological effects of catheter ablation of inferior vena cava-tricuspid
      annulus isthmus in common atrial flutter.
AB  - BACKGROUND: The electrophysiological mechanisms for successful catheter ablation
      of atrial flutter (AFI) targeting the inferior vena cava-tricuspid annulus (IVC
      TA) isthmus have not been determined. METHODS AND RESULTS: Twenty patients with
      common AFI were studied. All had inducible common AFI, and 8 of them had both
      common and reverse AFI. Right atrial (RA) activation sequences were investigated
      during pacing from sites proximal (low lateral RA) and distal (proximal coronary
      sinus) to the IVC-TA isthmus both during entrainment of common or reverse AFI and
      during pacing in sinus rhythm. This was repeated after ablation. During pacing in
      sinus rhythm from the low lateral RA, the septum was activated by caudocranial
      and craniocaudal wave fronts. Similarly, during pacing from the proximal coronary
      sinus, the lateral RA was activated by two wave fronts. Catheter ablation of the
      IVC-TA isthmus induced dramatic changes in mapping due to the loss of
      caudocranial wave front in all but 1 patient. The septum and the lateral RA were
      activated by a single craniocaudal front as during entrainment of reverse or
      common AFI, respectively. After a follow-up of 8 +/- 2 months, common or reverse
      AFI occurred in 4 patients. Two had no or only unidirectional changes in the
      isthmus conduction induced by ablation. The other 2 had a late recovery of
      conduction. CONCLUSIONS: The present study provides evidence that the mechanism
      of successful AFI ablation targeting the IVC-TA isthmus is local bidirectional
      conduction block. This change can be used as a new and complementary
      electrophysiological end point for the procedure. AFI recurrences are associated
      with failure to achieve a permanent block.

PMID- 8548902
TI  - RR interval variability in irregular monomorphic ventricular tachycardia and
      atrial fibrillation.
AB  - BACKGROUND: Algorithms to reject irregular tachyarrhythmias are available in
      implantable cardioverter-defibrillator devices to discriminate ventricular
      tachycardia (VT) from atrial fibrillation (AF). The hazard of underdetection of
      irregular monomorphic VTs using these algorithms has not yet been fully
      evaluated. The purpose of this study was to determine the ability of a commonly
      used stability algorithm to reject AF and to correctly detect VT with a high RR
      interval variability. METHODS AND RESULTS: The electrophysiological studies from
      232 patients with induced monomorphic VT (cycle length > 250 ms) and 21 with AF
      were reviewed. A preliminary analysis was performed to classify the VT episodes
      in irregular (successive RR differences > 20 ms after 4 seconds from onset) or
      regular (otherwise). Three study groups were defined: group 1 (27 patients with
      irregular VT), group 2 (22 randomly selected patients with regular VT), and group
      3 (21 patients with AF). A computer program analyzed the first 50 RR intervals of
      the induced VT (AF), resetting a VT counter if the interval was greater than a
      tachycardia detection interval (TDI) or if its absolute difference with the
      preceding three beats exceeded a programmed stability value (STAB). The VT was
      detected when the VT counter reached a preset number of intervals (NIDs).
      Different combinations of TDI, STAB, and NID were analyzed. All VTs in group 2
      were correctly detected. In contrast, up to 10 VTs from group 1 were not detected
      when high NIDs and low STAB parameters were programmed. With usual values (10 to
      16 beats and 50 to 60 ms, respectively), only 1 to 2 VTs remained undetected, but
      20% to 50% had a detection delay > 8 seconds. Undetected VTs were significantly
      slower than early detected VTs for most STAB and NID combinations. With usual
      stability and NID values, 10% to 20% of episodes of AF were inappropriately
      detected. Changes in TDI had a small impact on sensitivity and specificity when
      currently used values for stability were programmed. CONCLUSIONS: Animplantable
      cardioverter-defibrillator tachycardia detection algorithm with a stability
      criterion of 50 to 60 ms and 12 to 14 RR intervals is able to detect over 90% of
      monomorphic irregular VTs. Nevertheless, significant VT detection delays may
      arise, and inappropriate detection of AF cannot be totally prevented.

PMID- 8548903
TI  - Enhanced in vivo antithrombotic effects of endothelial cells expressing
      recombinant plasminogen activators transduced with retroviral vectors.
AB  - BACKGROUND: The effects of regulating endothelial cell (EC) plasminogen activator
      production on thrombus accumulation in vivo are incompletely understood. By
      overexpressing plasminogen activators in ECs via gene transfer, the hypothesis
      was tested that increased levels of plasminogen activators inhibit the
      accumulation of thrombus in vivo. METHODS AND RESULTS: Cultured baboon ECs
      transduced with human cDNAs for wild-type tissue plasminogen activator (TPA) or
      for glycosylphosphatidylinositol-anchored urokinase-type plasminogen activator (a
      UPA) were seeded onto collagen-coated segments of vascular graft (collagen
      segments) and exposed overnight to flow using an in vitro perfusion circuit. The
      antigenic levels of TPA and UPA each increased 10-fold in the media perfusing the
      corresponding transduced ECs compared with untransduced ECs (P < or = .05 in both
      cases). In baboons the antithrombotic effects of TPA-transduced or a-UPA
      transduced ECs were measured as 111In-platelet deposition and 125I-fibrin
      accumulation on collagen segments bearing sparsely attached ECs (tarnsduced
      versus untransduced) interposed in exteriorized arteriovenous femoral shunts.
      Platelet-rich thrombus formed on the collagen segments with fibrin-rich thrombus
      propagated distally. The presence of TPA-transduced or a-UPA-transduced ECs on
      collagen segments at a density of 25,000 ECs/cm2 decreased 111AIn-platelet
      deposition and 125I-fibrin accumulation on collagen surfaces compared with
      untransduced ECs present at equivalent density (P < .05 for platelet deposition
      with TPA-transduced ECs and P < .05 for platelet deposition on the propagated
      tail, as well as fibrin accumulation on the graft with a-UPA-transduced ECs). The
      systemic levels of fibrinopeptide A, thrombin-antithrombin complex, D-dimer, and
      both local and systemic levels of TPA and UPA were not increased by transduced
      ECs compared with untransduced ECs. The focal antithrombotic effects of
      transduced ECs appear to be due to local enhancement of thrombolysis.
      CONCLUSIONS: ECs transduced with recombinant TPA and a-UPA enhance local
      antithrombotic activity in vivo. This strategy of attaching transduced ECs
      overexpressing plasminogen activators may be therapeutically useful by preventing
      thrombo-occlusive failure of implanted cardiovascular devices or mechanically
      denuded vessels.

PMID- 8548904
TI  - Coupling between myosin ATPase cycle and creatinine kinase cycle facilitates
      cardiac actomyosin sliding in vitro. A clue to mechanical dysfunction during
      myocardial ischemia.
AB  - BACKGROUND: There is much evidence to support the favorable effects of the
      phosphocreatine shuttle on myocardial contraction and relaxation. However,
      experiments in which cardiac muscle fiber or myofibril was used have not
      elucidated its precise mechanism. METHODS AND RESULTS: Active movements of
      fluorescently labeled actin filaments on a cardiac myosin layer coimmobilized
      with creatinine kinase (CK) onto a nitrocellulose-coated glass coverslip were
      studied under various concentrations of adenine nucleotides. At a constant
      phosphocreatine concentration (5 mmol/L, pH 7.1), the relation of sliding
      velocity to MgATP concentration followed Michaelis-Menten kinetics. The apparent
      Km was significantly smaller in the presence of CK (0.041 +/- 0.001 mmol/L) than
      in the absence of CK (0.080 +/- 0.001 mmol/L), indicating that coattached CK
      facilitated the propelling of actin filaments by the myosin ATPase. This
      phenomenon was also seen under acidic conditions (pH 6.7) as well as in the
      presence of inorganic phosphate (10 mmol/L. At a constant MgATP concentration (1
      mmol/L), the inhibitory effect of MgADP on the actin-myosin interaction was
      weaker in the presence of CK than in the absence of CK. Another ATP-regenerating
      system, pyruvate kinase and phospho(enol)pyruvate, while maintaining a low ratio
      of [MgADP] to [MgATP], did not reduce the Km value (0.156 +/- 0.001 mmol/L),
      suggesting that the effect of coattached CK was not achieved only by prevention
      of MgADP accumulation. CONCLUSIONS: Coupling between the ATPase cycle and the CK
      cycle may serve not only to maintain the ATP concentration within the myofibril
      but also to provide optimal conditions for cardiac actomyosin interaction.
      Consideration of this coupling will offer a clue to elucidating the systolic or
      diastolic dysfunction during myocardial ischemia or reperfusion.

PMID- 8548905
TI  - Nitric oxide inhibits numerous features of mast cell-induced inflammation.
AB  - BACKGROUND: We previously reported that mast cell degranulation causes histamine
      and P-selectin-dependent leukocyte rolling and platelet-activating factor (PAF)-
      and CD18-associated leukocyte adhesion, whereas others have reported serotonin
      induced edema formation. The purpose of the present study was to determine
      whether nitric oxide (NO) could inhibit the mast cell-induced multistep
      recruitment of leukocytes and the associated microvascular dysfunction in single
      inflamed venules. METHODS AND RESULTS: Intravital fluorescence microscopy was
      used to demonstrate increased leukocyte rolling and adhesion and increased
      albumin extravasation in single 25- to 40-microns venules that were treated with
      the mast cell-degranulating agent compound 48/80 (CMP 48/80). The mast cell
      induced histamine-dependent rolling and PAF-dependent adhesion were completely
      inhibited by the addition of the NO donor spermine NO. However, spermine NO did
      not directly inhibit histamine-induced leukocyte rolling and only partly affected
      PAF-induced leukocyte adhesion. Compound 48/80-activated mast cells evoked a
      significant increase in PAF-dependent neutrophil adhesion in vitro. Spermine-NO
      prevented the mast cell-dependent neutrophil adhesion but failed to affect direct
      adhesion with PAF. The mast cell-induced albumin leakage was also inhibited by
      the NO donor. CONCLUSIONS: Taken together, these results suggest that exogenous
      NO can modulate leukocyte recruitment and microvascular permeability alterations
      elicited by mast cell activation and raises the possibility that the use of NO
      donors may be a reasonable therapeutic approach to reducing mast cell-dependent
      inflammation.

PMID- 8548906
TI  - Enhancement of platelet deposition by cross-linked hemoglobin in a rat carotid
      endarterectomy model.
AB  - BACKGROUND: Purified human cross-linked hemoglobin, which is now being used in
      clinical trials, increases mean arterial pressure through binding of nitric oxide
      (NO). We postulated that binding of NO by cross-linked hemoglobin (alpha alpha
      Hb) could also increase platelet deposition at sites of subintimal injury.
      METHODS AND RESULTS: Male Sprague-Dawley rats were infused with alpha alpha Hb
      (0.88 g/kg, n = 8) or with the NO synthase inhibitor NG-monomethyl-L-arginine (L
      NMMA, 30 mg/kg, n = 7) before undergoing microsurgical carotid endarterectomy.
      111In-labeled platelets were infused after endarterectomy, and platelet
      deposition was measured 20 minutes later. In control endarterectomized rats (n =
      8), mean platelet deposition was 7.7 +/- 0.7 x 10(6)/mm2. Platelet deposition was
      significantly increased above controls in rats that received alpha alpha Hb (13.2
      +/- 0.9 x 10(6)/mm2, P = .0004) and in rats infused with L-NMMA (13.9 +/- 1.0 x
      10(6)/mm2, P = .0002). The increase was prevented by infusion of L-arginine (150
      mg/kg) immediately after alpha alpha Hb or L-NMMA. To determine whether aspirin
      (ASA) blocked the increased deposition induced by alpha alpha Hb, rats received
      oral ASA (10 mg/kg) 18 hours before endarterectomy. Platelet deposition in
      animals receiving ASA alone was 6.4 +/- 0.9 x 10(6)/mm2 (n = 8). This was
      significantly increased to 10.8 +/- 0.8 x 10(6)/mm2 (P = .002) for the ASA
      treated group that received alpha alpha Hb at the time of endarterectomy (n = 8).
      The prolonged bleeding times induced by ASA were unaffected by the infusion of
      alpha alpha Hb. CONCLUSIONS: These data suggest that in a rat endarterectomy
      model, alpha alpha Hb increases platelet deposition at sites of subintimal injury
      by binding NO. Increased deposition induced by alpha alpha Hb can be prevented by
      administration of L-arginine but not by pretreatment with aspirin.

PMID- 8548907
TI  - Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease
      and preserves graft status in a murine model. A comparative study with captopril.
AB  - BACKGROUND: Despite the current progress in immunosuppressive regimens, the
      incidence of graft coronary artery disease (CAD) after cardiac transplantation
      has not decreased. Recent study has revealed that angiotensin-converting enzyme
      (ACE) inhibition decreases CAD in rats; however, it is not clear whether this
      beneficial effect of ACE inhibition is due to a decrease in production of
      angiotensin II (Ang II) or inhibition of bradykinin degradation. To determine
      whether Ang II type 1 receptor (AT1-R) blockade has an inhibitory effect on CAD,
      we evaluated the effects of TCV-116, an AT1-R antagonist, in a murine model of
      cardiac transplantation. METHODS AND RESULTS: Hearts of DBA/2 mice (H-2d) were
      transplanted heterotopically to B10.D2 mice (H-2d). Recipients were treated
      orally with TCV-116 (10 mg/kg per day), captopril (100 mg/kg per day), or vehicle
      only. Graft status, as assessed by palpation and inspection at laparotomy 70 days
      after transplantation, was preserved better in the TCV-116-treated group (P <
      .005) and in the captopril-treated group (P < .05) than in the vehicle-treated
      group. Intimal area in the graft coronary arterial wall decreased to 31% in the
      TCV-116-treated group (P < .001 versus vehicle-treated group) and to 34% (P <
      .005) in the captopril-treated group but was 45% in the vehicle-treated group.
      Fibrotic lesions of the left ventricle were less prominent in the TCV-116-treated
      (31%; P < .01 versus vehicle-treated group) and captopril-treated groups (33%; P
      < .05) than in the vehicle-treated group (54%). CONCLUSIONS: These findings show
      that AT1-R blockade is at least as effective as ACE inhibition in management of
      chronic allograft rejection and suggest that Ang II may play an important role in
      chronic allograft rejection.

PMID- 8548908
TI  - Adventitial remodeling after coronary arterial injury.
AB  - BACKGROUND: Intraluminal thrombus formation and medial smooth muscle (SM) cell
      proliferation are recognized responses of the arterial system to injury. In
      contrast to these well-characterized processes during vascular repair, changes
      involving the adventitia have been largely neglected in previous studies. Hence,
      the goal of this investigation was to assess the response of the adventitia to
      coronary arterial injury. METHODS AND RESULTS: Adventitial changes in porcine
      coronary arteries subjected to medial injury were characterized by
      immunohistochemistry, histochemistry, and microscopic morphometry. The rapid
      development of a hypercellular response in the adventitia was evident 3 days
      after balloon-induced medial injury. Cell proliferation, as assessed by
      proliferating cell nuclear antigen immunostaining, reached the maximum level in
      the adventitia at 3 days, whereas at 14 and 28 days, the number of replicating
      cells reverted toward the baseline. The proliferating activity in the adventitia
      exceeded that seen in the media at all times after injury. To further define the
      changes in the phenotype of adventitial cells, the expression of three
      cytoskeletal proteins (vimentin, alpha-SM actin, and desmin) was characterized.
      Fibroblasts in normal adventitia expressed vimentin but no alpha-SM actin or
      desmin. After injury, these cells acquired characteristics of myofibroblasts
      expressing alpha-SM actin, which peaked at 7 and 14 days. Desmin expression was
      patchy in the adventitia, as opposed to its homogeneous distribution in medial SM
      cells. The modulation of fibroblast phenotype was transient, inasmuch as alpha-SM
      actin immunostaining declined at 28 days after injury, when dense, collagen-rich
      scar was evident within the adventitia. The above-described changes involving
      hypercellularity of the adventitia, myofibroblast formation, and fibrosis were
      associated with a significant focal adventitial thickening at 3, 7, 14, and 28
      days after injury (P < .01 versus uninjured coronary arteries). CONCLUSIONS: This
      study demonstrates the involvement of the adventitia in the vascular repair
      process after medial injury. The hypercellularity of the adventitial layer,
      proliferation of fibroblasts, and modulation of their phenotype to myofibroblasts
      are associated with the development of the thickened adventitia. It is postulated
      that these phenomena affect vascular remodeling and may provide an important
      insight into the mechanisms of vascular disorders.

PMID- 8548909
TI  - Time-related normalization of maximal coronary flow in isolated perfused hearts
      of rats with myocardial infarction.
AB  - BACKGROUND: In the present study, we investigated the time dependency and
      regional differences of the vascular adaptation of the myocardium after
      myocardial infarction (MI) in rats. METHODS AND RESULTS: MI was induced by total
      occlusion of the left anterior descending coronary artery. Time-dependent
      adaptation of the coronary vasculature was determined by histological staining of
      endothelial cells and measurement of basal and maximal coronary flow at days 0,
      4, 7, 21, 35, and 90 after surgery in isolated retrogradely perfused hearts of
      sham-operated and infarcted rats. Cardiac function was determined during
      anterograde perfusion. In a separate group of experiments, regional myocardial
      flow was measured with radiolabeled microspheres in sham-operated and infarcted
      hearts to determine local differences in adaptation. Basal coronary flow was
      completely normalized within 7 days, whereas maximal coronary flow was not
      normalized until 35 days after MI. Normal growth, as observed in sham-operated
      hearts, resulted in a parallel increase in coronary flow and tissue mass from day
      7 to 35 after surgery. In contrast, the increase in coronary flow was lower than
      the hypertrophic response in the right ventricles and septa of infarcted hearts,
      whereas a parallel increase in tissue mass and coronary flow was observed in the
      left ventricles of these hearts. These functional data were supported by
      structural data that showed the presence of numerous and dilated vessels,
      especially in the border zone of the infarcted and noninfarcted tissue.
      CONCLUSIONS: These observations demonstrate that vessel growth, predominantly in
      the region adjacent to the infarcted zone, results in complete normalization of
      coronary vasodilatory capacity within 35 days after MI.

PMID- 8548910
TI  - Increased release of NO during ischemia reduces myocardial contractility and
      improves metabolic dysfunction.
AB  - BACKGROUND: We have reported that myocardial ischemia increases nitric oxide (NO)
      production. Several lines of evidence suggest that NO reduces myocardial
      contraction. Therefore, we tested whether endogenous NO decreases the inotropic
      response of the ischemic myocardium and whether endogenous NO is beneficial in
      the metabolic function of ischemic myocardium. METHODS AND RESULTS: The left
      anterior descending coronary artery was perfused with blood from the left carotid
      artery in 72 dogs. An infusion of NG-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of NO synthase, did not affect fractional shortening (FS) under
      nonischemic conditions. After reduction of perfusion pressure so that coronary
      blood flow decreased to 60% of the control value, FS of the perfused area
      decreased, and intravenous infusion of isoproterenol increased FS. Before and
      during intravenous infusion of isoproterenol under conditions of coronary
      hypoperfusion, FS was significantly increased in the L-NAME group compared with
      the untreated group. Both lactate extraction ratio and the pH in coronary venous
      blood were significantly lower in the L-NAME-treated group than in the untreated
      group during coronary hypoperfusion. Infusion of L-arginine prevented the effects
      of L-NAME in the ischemic myocardium. CONCLUSIONS: These results indicate that
      endogenous NO reduces myocardial contractile function and improves myocardial
      metabolic function in the ischemic heart. The myocardial energy-sparing effect as
      well as coronary vasodilation due to NO may be beneficial to the ischemic
      myocardium.

PMID- 8548911
TI  - Omega-3 lipid infusion in a heart allotransplant model. Shift in fatty acid and
      lipid mediator profiles and prolongation of transplant survival.
AB  - BACKGROUND: omega-3 Fatty acids may have a major impact on immune responses
      involved in heart transplant rejection. We compared the effects of posttransplant
      intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions
      on graft survival, plasma fatty acid profiles, and levels of arachidonic acid
      versus eicosapentaenoic acid-derived lipid mediators. METHODS AND RESULTS: Inbred
      PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a
      model of heterotopic heart transplantation. Animals received 9 g/kg body wt per
      day of either fish oil-derived (n = 8) or soybean oil-derived fat (n = 7) in the
      form of a continuously infused lipid emulsion; controls were sham-infused with
      saline (n = 8). Graft rejection was assessed by loss of activity of the
      transplant. The fish oil-derived preparation but not that originating from
      soybean oil caused an increase in total and free plasma fatty acids. Substantial
      quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free
      fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of
      neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series
      leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB5,
      omega-oxidation products of LTB5, LTA5 secretion), with 5-series/4-series LT
      ratios ranging between 0.08 and 0.36. Ratios of TX B3/B2 liberated from ex vivo
      stimulated platelets even approached 1:1 in omega-3 supplemented rats. Graft
      survival was 7.6 +/- 0.3 (mean +/- SEM) days in saline-infused, 10.4 +/- 0.7 in
      omega-6 lipid-infused, and 12.9 +/- 0.4 in omega-3 lipid-infused animals.
      CONCLUSIONS: Posttransplant intravenous alimentation with fish oil-derived lipid
      emulsions prolongs heart transplant survival in excess to omega-6 lipids.
      Profound changes in fatty acid profiles and lipid mediator generation may
      underlie this finding.

PMID- 8548912
TI  - Cellular basis for the electrocardiographic J wave.
AB  - BACKGROUND: The J wave is a deflection that appears in the ECG as a late delta
      wave following the QRS or as a small secondary R wave (R'). Also referred to as
      an Osborn wave, the J wave has been observed in the ECG of animals and humans for
      more than four decades, yet the mechanism underlying its manifestation is poorly
      understood. The present study investigates the cellular basis for the J wave
      using an isolated arterially perfused preparation consisting of a wedge of canine
      right or left ventricle. METHODS AND RESULTS: A 12-lead ECG was initially
      recorded in vivo. After isolation and arterial perfusion of the right or left
      ventricular wedge, transmembrane action potentials were simultaneously recorded
      from epicardial, M region, and endocardial transmural sites with three floating
      microelectrodes. A transmural ECG was recorded concurrently. A J wave was
      observed at the R-ST junction of the ECG in 17 of 20 adult dogs, usually in leads
      II, III, aVR, and aVF and the mid to lateral precordial leads. The J wave in the
      transmural ECG recorded across the wedge was closely associated with the presence
      of a prominent action potential notch in epicardium but not endocardium. The
      shape and amplitude of the J wave were found to depend on (1) the transmural
      distribution of the action potential notch amplitude, (2) the relative time
      course of the early phases of the action potential (width of notch) at different
      sites within the wall, (3) sequence of activation, and (4) conduction time across
      the wall. A highly significant correlation was demonstrated between the amplitude
      of the epicardial action potential notch and the amplitude of the J wave recorded
      during interventions that alter the appearance of the electrocardiographic J
      wave, including hypothermia, premature stimulation, and block of the transient
      outward current by 4-aminopyridine. Ventricular activation from endocardium to
      epicardium, with epicardium activated last, was also an important prerequisite
      for the appearance of the J wave. This sequence permits the establishment of a
      voltage gradient of the early phases of the action potential after activation
      (ie, the QRS) is complete. CONCLUSIONS: Our results provide the first direct
      evidence in support of the hypothesis that heterogeneous distribution of a
      transient outward current-mediated spike-and-dome morphology of the action
      potential across the ventricular wall underlies the manifestation of the
      electrocardiographic J wave. The presence of a prominent action potential notch
      in epicardium but not endocardium is shown to provide a voltage gradient that
      manifests as a J (Osborn) wave or elevated J-point in the ECG.

PMID- 8548913
TI  - A 73-year-old man with hypertension and syncope.

PMID- 8548914
TI  - Images in cardiovascular medicine. Impending paradoxical embolus.

PMID- 8548915
TI  - Predictors of survival in Chagas' heart disease.

PMID- 8548916
TI  - Apoptosis in human atherosclerosis and restenosis.

PMID- 8548917
TI  - Chelation therapy for intermittent claudication: a double-blind, randomized,
      controlled trial.

PMID- 8548918
TI  - Prediction of improvement of regional left ventricular function after surgical
      revascularization.

PMID- 8548919
TI  - Significance of CK values after coronary angioplasty.

PMID- 8548920
TI  - Atrial septal aneurysm in children.

PMID- 8548922
TI  - Effect of encapsulation on the anti-inflammatory properties of superoxide
      dismutase after oral administration.
AB  - Anti-inflammatory properties of free superoxide dismutase and superoxide
      dismutase encapsulated into liposomes, with or without ceramides, have been
      investigated. Two models were investigated: carrageenan paw oedema and pleurisy.
      Animals were fed by repeated doses, twice daily from day 1 until day 4.
      Evaluation consisted of measurement of paw oedema volume with determination of
      prostaglandin E2, thromboxane B2 and 6-keto-prostaglandin F1 alpha levels.
      Polymorphonuclear oxidative metabolism was evaluated by measurement of superoxide
      anion production. Levels of superoxide dismutase were determined in cells and
      pleural exudates. Higher anti-inflammatory effects were obtained after eight
      administrations of encapsulated forms (0.5 mg/kg) whereas free superoxide
      dismutase have shown no effects. Ceramides enhanced the results obtained.

PMID- 8548921
TI  - Evaluation of the decarbamylation process of cholinesterase during assay of
      enzyme activity.
AB  - The activity of carbamylated cholinesterase increases continuously during assay,
      suggesting that progressive decarbamylation takes place. The following effects of
      assay conditions on the observed decarbamylation were studied: the effect of the
      sulfhydryl group of nitrobenzoate produced in the course of Ellman assay, the
      effect of substrate and the effect of sample dilution during assay. This study
      indicates that sample dilution is the main trigger to the decarbamylation
      observed during assay of cholinesterase activity. The process was described as a
      first-order reaction during which the inhibited enzyme gives place to the active
      form. Kinetic constants for decarbamylation of human pseudocholinesterase (EC
      3.1.1.8) at 30 degrees C were approximately 0.005 min-1 for dimethylcarbamates
      and 0.010 min-1 for monomethylcarbamates, when 1 mmol/l propionylthiocholine was
      used as substrate.

PMID- 8548923
TI  - An improved spectrophotometric assay of pyruvate dehydrogenase in lactate
      dehydrogenase contaminated mitochondrial preparations from human skeletal muscle.
AB  - In mitochondria-enriched preparations of human skeletal muscle, the measurement
      of pyruvate dehydrogenase activity, as determined by conventional
      spectrophotometric assay of NADH accumulation, is underestimated due to the
      oxidizing activity of the contaminating lactate dehydrogenase. Using a model
      reaction system consisting of varying mixtures of purified lactate and pyruvate
      dehydrogenases, we found that the presence of oxamate, a competitive inhibitor of
      the lactate dehydrogenase, allowed the measurement of a linear rate of pyruvate
      dehydrogenase activity without interference from lactate dehydrogenase. In the
      presence of 25 mM oxamate, this holds true up to a ratio of 30:1 for lactate to
      pyruvate dehydrogenases, respectively. A similar result was obtained when using
      human skeletal muscle mitochondria contaminated by lactate dehydrogenase. Rates
      of pyruvate dehydrogenase activity ranging from 50 to 120 nmol/min/mg protein
      could be routinely measured in such mitochondrial fractions. We concluded that
      the use of oxamate allows a spectrophotometric assay for pyruvate dehydrogenase
      activity to be utilized when screening for pyruvate dehydrogenase deficiency in
      mitochondria-enriched preparations of human skeletal muscle.

PMID- 8548924
TI  - Development of an enzyme-linked immunosorbent assay to measure total TIMP-1 (free
      TIMP-1 and TIMP-1 in combination with matrix-metalloproteinases) and measurement
      of TIMP 1 and CRP in serum.
AB  - A panel of six monoclonal antibodies (MAbs) was raised against purified human
      fibroblast tissue inhibitor of metalloproteinase-1 (TIMP-1) and characterised.
      All possible antibody pairs were tested for their suitability as capture and
      revealing antibodies in a two-site enzyme-linked immunosorbent assay (ELISA) to
      measure total TIMP-1 (both free TIMP-1 and TIMP-1 together with matrix
      metalloproteinases (MMPs)). Using the best combination of MAbs the assay was
      optimised. The sensitivity of detection of the assay was 1.4 ng/ml, and inter-
      and intra-assay coefficients of variation were between 10.4-13.7% and 8.8-9.7%,
      respectively. Dilution series of human cerebrospinal and synovial fluids, plasma
      and sera paralleled those of the TIMP-1 standard curve indicating that the
      immunoreactivity detected in these samples was authentic TIMP-1. TIMP-2 shows no
      detectable cross reactivity in this assay confirming that this ELISA is specific
      for TIMP-1. The levels of total TIMP-1 and collagenase were measured in
      conditioned medium from A2058 human melanoma cells cultured in the absence or
      presence of human recombinant interleukin-1 alpha (hrIL-1 alpha). Total TIMP-1
      was also measured in serum samples with known C-reactive protein (CRP) (n = 100)
      and alpha 1 antichymotrypsin (ACT) (n = 52) concentrations; no correlation was
      found between TIMP-1 levels and either of these acute phase reactants although
      the levels of TIMP-1 were raised when compared to normal sera. This ELISA
      provides a rapid and convenient procedure for the quantitation of total TIMP-1 in
      human biological fluids and supernatants from cultured cell lines.

PMID- 8548925
TI  - Comparison of 5-hydroxyindole-acetic acid and para-amino hippurate clearances in
      newborn rabbits.
AB  - Recent study indicates that endogenous 5-hydroxyindole-acetic acid (5-HIAA)
      clearance can be used as an alternative procedure to para-amino hippurate (PAH)
      clearance for the estimation of renal plasma flow in human patients. In view of
      the limitations of PAH clearance measurements in newborn infants we made an
      attempt to validate the technique of measuring renal blood flow with 5-HIAA
      quantitatively against PAH clearance. Thirty-four simultaneous determinations of
      PAH and 5-HIAA clearances were performed in 14 newborn rabbits. 5-HIAA
      concentrations in plasma and urine were measured by using HPLC coupled with
      electrochemical detection (Beckman). Renal blood flow was found to range between
      0.60 and 6.90 ml/min/kg (mean: 3.39 ml/min/kg) for 5-HIAA and from 0.93 to 6.61
      ml/min/kg (mean: 3.68 ml/min/kg) for PAH clearances. There was a significant
      positive correlation between the values obtained by the two techniques (r = 0.84,
      P < 0.001). When 5-HIAA clearance was analyzed as a function of plasma 5-HIAA
      level only a weak, but statistically significant correlation could be detected (r
      = 0.33, P < 0.05). Plasma 5-HIAA measurement alone, therefore, does not reflect
      renal blood flow in newborn rabbits. It is concluded that endogenous 5-HIAA
      clearance might serve as a reliable estimate of renal blood flow in the neonate
      under different physiologic and pathologic conditions.

PMID- 8548926
TI  - Plasma protein leakage and local secretion of proteins assessed in sputum in
      asthma and COPD. The effect of inhaled corticosteroids.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are characterized by
      chronic airway inflammation with cell infiltration, increased plasma exudation
      and abnormal local secretion of proteins. We have analysed whether sputum differs
      in this respect between asthma (n = 9) and COPD (n = 9), and whether inflammatory
      markers in sputum are affected by treatment. In non-smoking asthma patients there
      was more plasma protein leakage, based on the relative coefficient of excretion Q
      alpha 2macroglobulin/QIgG (P = 0.03). There was less local secretion of sIgA and
      lactoferrin than in COPD (P < 0.05). Tryptase was slightly higher in sputum from
      asthma than from COPD (P < 0.05), whereas eosinophil cationic protein and
      myeloperoxidase were similar. After treatment with glucocorticosteroids, there
      was a reduction in the Q alpha 2macroglobulin/Qalbumin (P < 0.015), but no effect
      was seen on the levels of products from local cells. We conclude that sputum
      analysis is useful to study the local inflammatory process in asthma and COPD.

PMID- 8548927
TI  - Elastase binding capacity of alpha 2-macroglobulin and its association with
      glucocorticoid concentration in southern African black patients with
      hepatocellular carcinoma.
AB  - Thirty-three Southern African black patients with hepatocellular carcinoma (HCC)
      (7 women) and 43 black control individuals (14 women), all in the age group 18-45
      years, were investigated for plasma alpha 2-macroglobulin (alpha 2M) elastase
      binding capacity (EBC). Cortisol levels were measured in 15 (3 women) of the HCC
      patients and 10 (5 women) of the control subjects. A significant difference in
      EBC was found between the HCC patients and the control subjects (P < 0.001). A
      significant difference was also found in cortisol levels between the two groups
      (P < 0.001). A significant correlation between EBC and cortisol levels was
      obtained (r = 0.57; P < 0.042). The significant increase in EBC of alpha 2M in
      HCC patients could be due to an increase in circulating cortisol.

PMID- 8548928
TI  - Separation of T and B lymphocytes from human peripheral blood mononuclear cells
      using density perturbation methods.
AB  - The fractionation of sub-populations of peripheral blood mononuclear cells has
      become an essential routine procedure and some of the main fractionation methods
      used today are immunomagnetic separations. We describe a less expensive method
      for the separation of subpopulations of mononuclear cells using density
      perturbation, which uses the binding of antibody-coated dense polystyrene beads
      to increase the density of specific sub-populations of cells. By incubating a
      total mononuclear fraction from human peripheral blood together with antibody
      coated beads, in a commercially-available lymphocyte separation medium (Nycoprep
      1.077), a depletion of 94.9 +/- 1.68% of the T cells could be obtained by this
      procedure; a depletion of 69.7 +/- 1.78% of the B cells was also achieved. These
      results indicate the potential for the separation of different sub-populations of
      peripheral blood mononuclear cells on the basis of the immunological identity of
      the surface of cells using density perturbation methods involving antibody-coated
      dense polystyrene beads.

PMID- 8548929
TI  - An improved GLC method for a rapid, simultaneous analysis of both medium chain
      fatty acids and medium chain triglycerides in plasma.
AB  - An improved gas-liquid chromatographic (GLC) method for the direct, simultaneous
      analysis of both medium chain monocarboxylic acids (MCFA) and medium chain
      triglycerides (MCT) is reported. The calibration curve of MCFA and MCT is linear
      in the range from 30 ng to 1000 ng. Five nanograms for tricaproin (MCT-6), 10 ng
      for tricaprylin (MCT-8) and 15 ng for tricaprin (MCT-9) represent the GLC
      detection limits of MCT, while those of MCFA range from 40 to 15 ng depending on
      their chain length: the longer the chain length, the higher the detection limit.
      The recovery of MCFA range from 79 to 99% and that of MCT from 85 to 99%. An
      example of plasma concentration curves of MCT and MCFA after an intravenous bolus
      injection of an MCT emulsion (100 mg MCT/kgbw) in a patient with Crohn's disease
      is shown.

PMID- 8548930
TI  - Preferential depletion of selenoprotein P in hypercholesterolaemic patients
      treated by LDL-apheresis.

PMID- 8548931
TI  - Tartrate resistant acid phosphatase in the serum of patients with larynx
      carcinoma--a marker of osteoclast activation.

PMID- 8548932
TI  - Susceptibility to copper oxidation of neuraminidase-treated LDL.

PMID- 8548933
TI  - The Birmingham pituitary database: auditing the outcome of the treatment of
      acromegaly.
AB  - BACKGROUND: Reduction of GH concentrations in acromegalic subjects may improve
      the increased mortality associated with the condition. Audit of the biochemical
      outcome of the management of acromegaly is, therefore, important. OBJECTIVES: (1)
      To audit the biochemical 'cure' rate of acromegalic patients treated by surgery
      and/or radiotherapy under the care of the South Birmingham Endocrine Clinic. (2)
      To assess the correlation between random or basal GH with IGF-I and nadir GH
      during an oral glucose tolerance test. DESIGN AND MEASUREMENTS: Ascertainment of
      acromegalic patients from a pituitary database. Mode of therapy, pretreatment GH,
      pretreatment tumour size, post-treatment GH, post-treatment IGF-I and post
      treatment nadir GH were recorded. Biochemical cure was defined as a most recent
      random or basal GH < 5 mU/l. Cure rates were determined. PATIENTS: Eighty-nine
      acromegalic patients were identified as having received surgery and/or
      radiotherapy. In 35/89 (39%) the most recent GH was < 5 mU/l. The cure rate
      following surgery was 26/78 (33%). This was not significantly associated with
      tumour size, but was associated with pretreatment GH concentration (chi 2 = 7.1,
      2d.f., P < 0.05). Random/basal GH showed a log-linear association with IGF-I, r =
      0.72, and a linear association with nadir GH, r = 0.93. CONCLUSIONS: Biochemical
      cure of acromegaly was more strongly associated with pretreatment GH than with
      tumour size. Random/basal GH measurements are useful and convenient for the audit
      of treatment outcome in acromegaly. Ways of improving the biochemical outcome of
      acromegaly should be sought.

PMID- 8548934
TI  - Localization of parathyroid tumours.

PMID- 8548935
TI  - Utility of 99mTc-sestamibi scintigraphy as a first-line imaging procedure in the
      preoperative evaluation of hyperparathyroidism.
AB  - OBJECTIVE: The use of preoperative imaging in patients with hyperparathyroidism
      remains controversial. Many of the available techniques are insufficiently
      sensitive and specific to justify their routine use. We have evaluated the
      sensitivity and specificity of 99mTc-sestamibi scintigraphy in the management of
      patients with different forms of hyperparathyroidism. DESIGN: Preoperative
      imaging evaluation was carried out by scintigraphic detection of pathological
      parathyroid glands using 99mTc-sestamibi as a radiotracer; confirmation of scan
      findings was obtained surgically. PATIENTS: A group of 25 patients with primary
      (n = 21) or secondary (n = 4) hyperparathyroidism were studied. All were
      considered for surgical treatment. MEASUREMENTS: In all cases parathyroid imaging
      was carried out by 99mTc-sestamibi scintigraphy together with at least one other
      imaging technique which included CT-scan, ultrasonography, MRI or 201TI/99mTc
      subtraction scintigraphy. Blood tests included measurements of total calcium and
      PTH. RESULTS: 99mTc-sestamibi scintigraphy correctly localized 20 out of 21
      adenomas, giving a sensitivity of 95.2%, markedly higher than that obtained with
      the other imaging techniques (ultrasonography 75%, 201TI/99mTc subtraction
      scintigraphy 57.1%, CT-scan 41.7% and MRI 33%). Of a total of 17 glands
      identified surgically as hyperplastic and confirmed by pathological examination,
      99mTc-sestamibi scintigraphy showed a positive image in 10, corresponding always
      to the larger abnormal glands (sensitivity 58.8%, higher than that observed with
      the other techniques). No false positive images were obtained with 99mTc
      sestamibi. All the ectopic adenomas (n = 3) were identified preoperatively, which
      contributed significantly to the surgical approach. CONCLUSION: In patients with
      hyperparathyroidism, 99mTc-sestamibi scintigraphy may be used as the single
      imaging technique as it shows a very high sensitivity and specificity in the
      preoperative localization of pathological parathyroid glands; the benefit of
      localizing parathyroid tissue prior to surgery in cases of ectopic adenomas
      clearly indicates that when an imaging procedure is required, this technique may
      be of great help in the management of hyperparathyroidism.

PMID- 8548936
TI  - Vitamin D intoxication causes hypercalcaemia by increased bone resorption which
      responds to pamidronate.
AB  - OBJECTIVE: Vitamin D intoxication is a relatively rare but treatable cause of
      hypercalcaemia. In the past this has been undertaken using corticosteroids.
      Previous observations have suggested that there is increased bone resorption in
      hypervitaminosis D. If this were to be the case, specific inhibitors of bone
      resorption might provide more effective treatment. We have therefore studied the
      mechanisms of hypercalcaemia and response to therapy in a group of patients with
      vitamin D intoxication. DESIGN: Vitamin D metabolites were measured in six
      patients with vitamin D intoxication; in five of these the components of
      hypercalcaemia were calculated. These measurements were repeated following
      treatment with corticosteroids (two patients) or the bisphosphonate, pamidronate
      (three patients). RESULTS: In each case the serum 25-hydroxyvitamin D was grossly
      elevated and there was a more modest elevation in serum 1,25-dihydroxyvitamin D.
      The components of hypercalcaemia suggest that there was a significant degree of
      bone resorption in all six patients and that this is the major determinant of
      hypercalcaemia. Pamidronate treatment resulted in a brisk reduction in plasma
      calcium concentration. Following corticosteroids the return of calcium to normal
      was more delayed. CONCLUSION: The hypercalcaemia of vitamin D intoxication is
      mediated by increased bone resorption and bisphosphonates have a role in its
      management.

PMID- 8548937
TI  - Diagnostic and clinical features in azoospermia.
AB  - BACKGROUND AND OBJECTIVE: The recent advances in assisted fertilization and
      gamete micromanipulation techniques have enabled fertilization in some forms of
      azoospermia; for example, epididymal sperm aspiration in obstructive azoospermia.
      Therefore knowledge of the specific degree of testicular damage is of primary
      importance, since other clinical parameters, such as FSH plasma levels and
      testicular volume, do not discriminate between the different testiculopathies. In
      order to further characterize the specific testicular conditions present in
      azoospermia, we have examined a large group of azoospermic subjects on the basis
      of testicular cytological analysis obtained by fine needle aspiration. DESIGN AND
      PATIENTS: One hundred and twenty-two infertile, azoospermic men were studied by
      physical examination, FSH radioimmunoassay, testicular ultrasound examination and
      fine needle aspiration of the testes. Thirty-five infertile normozoospermic
      subjects were studied as controls. RESULTS: The cytological analysis identified
      five different sub-types in azoospermic subjects: I, Sertoli cell-only syndrome;
      II, hypospermatogenesis; III, spermatogonial and/or spermatocytic arrest; IV,
      spermatidic arrest; and V, normal germ line. The testicular volume was reduced in
      groups I and II, while the FSH plasma levels were increased in groups I, II and
      III, suggesting a primary role of spermatids in the control of FSH secretion.
      CONCLUSIONS: In azoospermic subjects, testicular cytological analysis permits the
      identification of different sub-types and this classification may be very
      important in determining therapy, particularly the choice between surgical
      treatment and the hypothetical use of assisted fertilization techniques by
      retrieval of epididymal or intratesticular spermatozoa or spermatids.

PMID- 8548938
TI  - A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of
      Cushing's syndrome.
AB  - OBJECTIVE: The diagnosis of Cushing's syndrome remains a major challenge in
      clinical endocrinology. Various screening tests are commonly used to support a
      biochemical diagnosis in the context of clinical suspicion. The aim of this study
      was to compare the sensitivity in the diagnosis of Cushing's syndrome of a single
      in-patient sleeping midnight cortisol to a standard 48-hour in-patient low-dose
      dexamethasone suppression test (LDDST) during the same admission. DESIGN: A
      retrospective analysis was performed on 150 patients investigated in our
      department between the years 1970 and 1994 with a confirmed diagnosis of
      Cushing's syndrome. PATIENTS: One hundred and fifty patients with a diagnosis of
      Cushing's syndrome were analysed: 110 with Cushing's disease; 12 with tumours
      with ectopic ACTH secretion; 8 with ACTH dependent Cushing's syndrome of so far
      undetermined origin; 17 with cortisol secreting adrenal tumours; 3 with
      adrenocortical nodular hyperplasia. Twenty normal volunteers and nine patients
      with non-endocrine conditions were also investigated as controls. MEASUREMENTS:
      Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients
      presenting after 1980, and by fluorimetry prior to this date. RESULTS: In all the
      control subjects the sleeping midnight cortisol was < 50 nmol/l, below the lowest
      standard of the routine in-house RIA. In every patient with Cushing's syndrome
      the sleeping midnight cortisol was detectable with a value greater than 50
      nmol/l, with a range of 70-2000 nmol/l. In contrast, in three cases, all of whom
      had proven Cushing's disease on histology, there was uncharacteristic complete
      suppression of plasma cortisol to < 50 nmol/l following the LDDST. CONCLUSION: In
      this series of 150 cases, a single in-patient sleeping midnight cortisol above 50
      nmol/l had a 100% sensitivity for the diagnosis of Cushing's syndrome, clearly
      different from normal subjects. In contrast, the low-dose dexamethasone
      suppression test had a sensitivity of 98% even when the drug was administered as
      an in-patient. We recommend that a low-dose dexamethasone suppression test should
      not be used alone for confirmation of Cushing's syndrome since it may miss 2% of
      cases.

PMID- 8548939
TI  - A study of untreated Graves' patients with undetectable TSH binding inhibitor
      immunoglobulins and the effect of anti-thyroid drugs.
AB  - OBJECTIVE: We previously reported the clinical characteristics of Graves' disease
      with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit,
      but a study of the prognosis of untreated TBII negative patients with anti
      thyroid drug medication has never been undertaken. The aim of this paper is to
      study the difference between negative and positive TBII Graves' disease in
      relation to the effect of anti-thyroid drug treatment. PATIENTS: From January
      1986 to April 1991, 1545 patients with untreated Graves' disease were referred to
      Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified.
      Another 83 TRAb positive patients were randomly selected from the other Graves'
      disease patients and served as a comparison group. Fifty-six of the 94 patients
      in the TBII negative group and 52 of the 83 patients in the TBII positive group
      completed treatment with methimazole only. MEASUREMENTS: The trial was conducted
      as a retrospective study with a maximum treatment period of 36 months and a
      follow-up period of a further 12 months. From the original pool of patients, we
      classified 56 TBII negative patients into two groups according to the clinical
      course taken; Group A in whom TBII remained undetectable throughout methimazole
      treatment (9 men and 34 women, age 37.2 +/- 2.2 years), and Group B who became
      TBII positive (4 men and 9 women, 31.2 +/- 4.4 years). Fifty-two TBII positive
      patients served as the comparison Group C (8 men and 44 women, age 38.1 +/- 2.0
      years). RESULTS: Serum free T4 and free T3 levels in groups A and B were
      significantly lower before treatment than those of Group C (P < 0.001). The
      thyroid volumes of Group A and B patients were significantly smaller than those
      of Group C (P < 0.01). The level of TBII in Groups A and B was significantly
      lower than that in Group C (8.3 +/- 0.7 and 8.8 +/- 1.1 vs 57.0 +/- 2.8%,
      respectively, P < 0.001). The level of thyroid stimulating antibody (TSAb) in
      Groups A and B was significantly lower than that in Group C (478 +/- 71.0 and 761
      +/- 140.3 vs 2143 +/- 280%, respectively, P < 0.01), and there were no
      significant differences in TSAb activities between Groups A and B. The remission
      rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data
      indicate that Group A has a good prognosis, but Group B has the same prognosis as
      Group C. CONCLUSION: We conclude that patients in whom TSH binding inhibitor
      immunoglobulins remained negative have a much better prognosis than TSH binding
      inhibitor immunoglobulins positive patients or those who become TSH binding
      inhibitor immunoglobulins positive, having been initially negative.

PMID- 8548940
TI  - Treatment of post-menopausal osteoporosis with a combination of growth hormone
      and pamidronate: a placebo controlled trial.
AB  - OBJECTIVE: It is known that growth hormone can induce accelerated bone turnover
      in GH deficient people as well as healthy elderly people. In this study we
      examined the effect of recombinant human GH (rhGH) on bone mineral mass and bone
      turnover in the presence of the bone resorption inhibiting agent, pamidronate.
      Effects on body composition were also studied. METHODS: Twenty-one post
      menopausal osteoporotic women were treated with the bisphosphonate pamidronate
      during 12 months. During the initial 6 months rhGH (0.0675 IU/kg, 3 times/week)
      was administered in a placebo controlled fashion (10 vs 11 patients).
      MEASUREMENTS: Bone mineral content (BMC) of the lumbar spine and femoral neck was
      measured with dual-energy X-ray absorptiometry and BMC of the distal and proximal
      forearm with single-photon absorptiometry. Body composition was measured with
      bioelectrical impedance and total body dual-energy X-ray absorptiometry. Serum
      IGF-I and biochemical indices of bone turnover were also measured. RESULTS: The
      group treated with rhGH showed a two to three-fold increase in serum IGF-I
      levels. No effects on bone mineral mass were observed in the group treated with
      rhGH, either after the initial 6 months of treatment with rhGH or after the total
      period of 12 months. In women treated with pamidronate, however, a consistent
      increase of about 5% at the lumbar spine and somewhat less in the distal forearm
      was reached from 6 months onwards. In neither group was any change observed in
      BMC at the femoral neck or forearm. Compared to baseline, the biochemical
      measurements of bone turnover showed a decrease of about 50% in the pamidronate
      treated group, but this effect was blunted in the group additionally treated with
      rhGH. The body composition measurements showed clear effects of rhGH
      administration: a decrease in fat mass of about 5% and an increase in lean body
      mass of about 3%. However, these effects disappeared after the treatment with
      rhGH was stopped and both fat mass and lean body mass returned to initial values.
      CONCLUSIONS: The present study suggests that treatment with rhGH blunted both the
      pamidronate induced accumulation of bone mineral mass and the reduction of
      biochemical markers of bone turnover. Furthermore, the positive effect of rhGH on
      body composition disappears completely after cessation of treatment with rhGH.

PMID- 8548941
TI  - The 'dawn phenomenon' in adolescents with insulin dependent diabetes mellitus:
      possible contribution of insulin-like growth factor binding protein-1.
AB  - OBJECTIVE: Insulin resistance increases during adolescence, and is exaggerated in
      patients with insulin dependent diabetes mellitus (IDDM). A relative deficiency
      of insulin-like growth factor-I (IGF-I) may contribute to this increased insulin
      requirement. Two mechanisms have been proposed: (a) increased GH secretion,
      caused by failure of IGF feedback control, leading to increased insulin
      resistance and (b) lack of insulin-like action of the IGFs which is reinforced by
      high plasma levels of IGFBP-1, an inhibitor of IGF action. The contribution of
      these two mechanisms to the 'dawn phenomenon' is assessed. DESIGN: The two
      possible mechanisms were studied during the dawn rise of glucose in pubertal
      adolescent patients with IDDM. Two overnight studies were performed in each
      subject. Patients remained on the same insulin regimen throughout. SUBJECTS:
      Twenty-two diabetic adolescent subjects, aged (mean +/- SEM) 14.0 +/- 0.4 years,
      duration of IDDM 7.9 +/- 0.8 years, were recruited. Pubertal status was: group 1
      (breast stage 1-2; testicular volume < 4-8 ml) 3 male and 4 female, group 2
      (breast stage 3; testicular volume 10-12 ml) 0 male 4 female, group 3 (breast
      stage 4-5; testicular volume 15-25 ml) 4 male and 7 female. Height standard
      deviation score (mean +/- SD) (-0.02 +/- 0.99) and daily insulin dose (50.4 +/-
      3.1 U/day) did not change between studies. There were no differences in HbA1
      (study A 11.26 +/- 0.45%, study B 11.09 +/- 0.42%). METHODS: The subjects were
      admitted for the two studies 0.3 +/- 0.03 years apart. Blood samples were taken
      via an indwelling cannula every 20 minutes between 1900 and 0700 h. MEASUREMENTS:
      GH was assayed every 20 minutes, IGFBP-1, glucose and free insulin every hour and
      IGF-I at 0700 h. GH, IGFBP-1, IGF-I and free insulin were measured by
      radioimmunoassay. IGFBPs were also analysed by Western ligand blotting
      techniques. GH profiles were analysed by Pulsar and results compared by paired
      Student's t-test. The relations between the dawn rise in glucose and the changes
      in IGFBP-1, GH and free insulin were examined by multiple linear regression
      analysis. RESULTS: Serum IGFBP-1 levels rose overnight in the two studies (study
      A, from 9 +/- 1 at 2200 to 59 +/- 9 micrograms/l at 0700 h; study B, from 10 +/-
      1 at 2100 to 64 +/- 14 micrograms/l at 0700 h) whilst insulin levels fell from 47
      +/- 5 at 2200 to 16 +/- 2 mU/l at 0700 h (study A) and from 45 +/- 5 at 2000 to
      14 +/- 2 mU/l at 0700 h (study B). Glucose levels fell from 16.0 +/- 1.0 to 9.3
      +/- 0.9 mmol/l at 0400 h, and then rose to 11.9 +/- 1.1 mmol/l at 0700 h during
      study A, and from 13.4 +/- 1.3 to 10.1 +/- 1.1 mmol/l at 0400 h and then rose to
      13.5 +/- 1.0 mmol/l at 0700 h during study B. There were no differences in GH
      secretion between studies (mean GH levels (mean +/- SD) (study A, 15.7 +/- 6.6
      mU/l; study B, 16.2 +/- 7.1 mU/l; correlation within subjects between studies r =
      0.77, P < 0.001), sum of GH peaks (study A, 189.9 +/- 90.3 mU/l; study B, 185.8
      +/- 100.2 mU/l; r = 0.57, P = 0.006)). Mean GH levels varied with pubertal stage
      (group 1, 12.1 +/- 1.5 mU/l; group 2, 23.3 +/- 2.1 mU/l; group 3, 15.3 +/- 1.2
      mU/l). Serum IGF-I levels were not different (study A, 203 +/- 12 micrograms/l;
      study B, 218 +/- 13 micrograms/l). REGRESSION ANALYSIS: The change in plasma
      glucose between 0200 and 0700 h in both studies related to free insulin, IGFBP-1
      and the sum of the GH levels over the preceding hour (log glucose = 7.87 + 5.32
      log IGFBP-1 (P = 0.0001) - 5.05 log free insulin (P = 0.0001) - 1.44 log GH (P =
      0.004); R2 = 72%). Mean overnight GH levels did not predict the morning rise in
      plasma glucose. CONCLUSION: The morning rise of IGFBP-1 and plasma glucose appear
      to be related in this group of subjects with IDDM and this was a consistent
      finding in the two studies. This relation was additive to the effect of insulin
      deficiency.

PMID- 8548942
TI  - Clinical efficacy and safety of low-dose flutamide alone and combined with an
      oral contraceptive for the treatment of idiopathic hirsutism.
AB  - BACKGROUND AND OBJECTIVE: High doses of flutamide, which is the only antiandrogen
      that specifically blocks the androgen receptor, have recently been used with good
      clinical results in women with hirsutism. Since regression of hair growth
      requires long-term therapy, clinical and economic considerations are important.
      The use of the lowest efficacious dosage could reduce costs. This study was
      undertaken to compare safety and efficacy of a low dose of flutamide (125 mg
      twice daily) alone and in combination with a triphasic oral contraceptive (OC) in
      women with idiopathic hirsutism. PATIENTS: Flutamide was administered orally in a
      low dose of 125 mg twice daily for 12 months alone in women with no risk of
      pregnancy or during the use of an oral contraceptive. MEASUREMENTS: Women were
      seen every 3 months and were evaluated for hirsutism score, hormone and lipid
      measurements. DESIGN: The study, which was conducted as a prospective open trial,
      was proposed to patients with idiopathic hirsutism, that is, with serum androgen
      levels in normal range and LH/FSH ratio less than 2. RESULTS: A statistically
      significant decrease in hirsutism score as compared to baseline was observed
      after only 3 months with either treatment, flutamide alone (16.9 +/- 1.6 vs 14.2
      +/- 1.7, P < 0.0001) or the combination of flutamide with OC (15.6 +/- 0.8 vs
      11.9 +/- 0.8, P < 0.001). Three months after cessation of treatment a
      statistically significant decrease from baseline was observed in the two groups.
      Nevertheless, at 6 months post-treatment this decrease was still significant only
      in the group who took flutamide in combination with an oral contraceptive.
      Flutamide alone does not appear to modify the levels of lipoproteins. The
      association of flutamide with a triphasic formulation significantly increased the
      HDL-C levels. CONCLUSIONS: This study shows beneficial effects of a low dose of
      flutamide in women with idiopathic hirsutism. The addition of an oral
      contraceptive is judicious to prevent pregnancy and reduce recurrence of
      hirsutism after cessation of flutamide. Peripheral androgenic blockage does not
      modify lipid profiles and it might reduce the negative effect of oral
      contraceptive on HDL-C levels. The addition of electrolysis delays the recurrence
      of hirsutism after cessation of flutamide.

PMID- 8548944
TI  - Evidence for an altered luteinizing hormone sensitivity to naloxone in
      pathological hyperprolactinaemia.
AB  - OBJECTIVE: The underlying mechanisms involved in the pathogenesis of amenorrhoea
      in hyperprolactinaemic states still remain unclear. Conflicting information
      exists on the role of endogenous opiates on gonadotrophin disturbances in this
      pathological condition. In this study we have undertaken a detailed investigation
      of LH and PRL secretion before and during administration of naloxone, an opioid
      receptor blocker, in hyperprolactinaemic women with or without ovarian function
      in order to assess the role of ovarian steroids upon naloxone induced LH and PRL
      release. DESIGN: Five anovulatory and six ovulatory subjects with
      hyperprolactinaemia were studied before and during naloxone infusion. Five normo
      prolactinaemic ovulatory subjects were included as controls. All ovulatory
      subjects were studied during the luteal phase of a menstrual cycle. Blood was
      sampled every 10-20 minutes over a 16-hour period on two alternate days. On study
      day 1 (control day), subjects received two sets of saline infusion every 6 hours
      and one saline bolus at the beginning of the seventh hour; on study day 3
      (naloxone day), they received a saline infusion during the first 6 hours, an
      intravenous bolus of naloxone (20 mg) at the beginning of the seventh hour and
      then a continuous naloxone infusion (1.6 mg/hour) during the ensuing 6 hours.
      Pituitary LH responsiveness and reserve were assessed on both study days by the
      subsequent administration of 5 and 95 micrograms of GnRH 4 hours before the
      completion of each sampling period. MEASUREMENTS: Serum concentrations of LH,
      PRL, oestradiol and progesterone were determined by radioimmunoassay. LH and PRL
      pulse detection and characteristics were analysed by the Cluster program.
      RESULTS: Serum PRL levels in hyperprolactinaemic anovulatory and ovulatory
      subjects were significantly elevated above the normal range. Oestradiol and
      progesterone serum levels during the luteal phase in women with
      hyperprolactinaemia and regular menses were similar to those in control ovulatory
      subjects. Mean LH concentrations increased during naloxone infusion (P < 0.05) in
      ovulatory hyperprolactinaemia and controls, whereas PRL increased (P < 0.05) only
      in the group of control subjects. LH pulse amplitude and pulse interval were
      increased by naloxone (P < 0.05) in all the ovulatory subjects, with no
      significant changes in anovulatory hyperprolactinaemic women. PRL pulse
      characteristics were modified significantly by naloxone only in the control
      group. On day 1, GnRH administration increased LH in all groups, whereas a
      consistently lower pituitary LH response was observed after naloxone (day 3).
      Serum PRL levels significantly increased after GnRH administration on day 1 only
      in normal women, whilst on day 3 this GnRH-dependent PRL releasing effect was
      significantly attenuated. CONCLUSIONS: The absence of stimulatory effects of
      naloxone on LH in anovulatory hyperprolactinaemia implies that endogenous opiates
      do not play a significant role in the mechanisms governing hypothalamic
      amenorrhoea in this syndrome. The results in subjects with ovulatory
      hyperprolactinaemia suggest the existence of an active role of ovarian steroids
      on naloxone induced LH release. These data, along with those previously reported
      in normal women throughout the menstrual cycle, are consistent with the concept
      that sex steroid hormones contribute to the underlying mechanisms involved in the
      opioidergic control of LH and PRL release. Whether PRL by itself or through other
      non-opioid neuroendocrine pathways alters the hypothalamic-gonadotroph unit still
      requires further investigation.

PMID- 8548943
TI  - Low circulating IGF-I levels in hyperthyroidism are associated with decreased GH
      response to GH-releasing hormone.
AB  - OBJECTIVE: Several abnormalities in the GH response to pharmacological stimuli
      have been described in hyperthyroidism. Both normal and high serum IGF-I levels
      have been reported, as well as a decrease in IGF-I bioactivity. We have evaluated
      the GH response to GH-releasing hormone (GHRH) in hyperthyroid patients and the
      effects of hyperthyroidism on serum IGF-I levels. The possible relations between
      nutritional status, thyroid hormones and IGF-I levels were also investigated. We
      also studied the influence of long-term beta-adrenoceptor blockade on the GH
      response to GHRH in these patients. DESIGN: In 18 hyperthyroid patients and in 12
      control subjects, GHRH (100 micrograms) was administered as an i.v. bolus
      injection. Eight hyperthyroid patients and 8 control subjects received 50
      micrograms GHRH i.v. Seven hyperthyroid patients were reevaluated after beta
      adrenoceptor blockade. IGF-I and albumin levels were measured initially in all
      hyperthyroid patients and control subjects. Body composition was determined in 11
      hyperthyroid patients and in a group of 33 matched normal controls. PATIENTS:
      Hyperthyroid patients were compared to control subjects. MEASUREMENTS: GH, TSH
      and free T4 were measured by immunofluorometric assay. IGF-I, total T3 and total
      T4 were measured by radioimmunoassay. Body composition was determined using a
      dual-energy X-ray absorptiometer. RESULTS: The GH response to 100 micrograms GHRH
      in hyperthyroid patients was blunted compared to control subjects. The mean peak
      GH levels and the area under the curve were significantly lower in hyperthyroid
      patients compared to control subjects (11 +/- 1 vs 27 +/- 5 micrograms/l and 820
      +/- 113 vs 1879 +/- 355 micrograms/l 120 min, respectively; P < 0.01). IGF-I
      levels were significantly reduced in hyperthyroid patients compared to controls
      (131 +/- 10 vs 201 +/- 16 micrograms/l, respectively; P < 0.01). Ideal body
      weight, serum albumin levels and the lean body mass were also reduced in
      hyperthyroid patients. After beta-adrenoceptor blockade there were no changes in
      the blunted GH response to GHRH in hyperthyroid patients. CONCLUSION: Our data
      suggest that the blunted GH response to GHRH in hyperthyroidism is apparently not
      related to circulating IGF-I levels. It is possible that nutritional factors
      could play a role in the reduced circulating IGF-I levels found in these
      patients.

PMID- 8548945
TI  - Androgens and insulin resistance in type 1 diabetic men.
AB  - OBJECTIVE: In healthy men, both high and low serum testosterone concentrations
      are associated with insulin resistance, whereas low concentration of sex hormone
      binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our
      study was to examine the association of sex hormones, SHBG,
      dehydroepiandrosterone (DHEAS) and insulin-like growth factor binding protein-1
      (IGFBP-1) on insulin sensitivity in type 1 diabetic patients. PATIENTS: We
      examined 23 male patients with the mean age of 29 +/- 1 years, body mass index
      22.9 +/- 0.4 kg/m2, insulin dose 47 +/- 3 units/day, glycosylated haemoglobin
      (HbA1c) 7.8 +/- 0.3% and duration of diabetes 13 +/- 1 years. DESIGN: Each
      patient was studied with a 4-hour euglycaemic (5.5 +/- 0.1 mmol/l),
      hyperinsulinaemic (612 +/- 26 pmol/l) clamp with indirect calorimetry. Muscle
      biopsies (quadriceps femoris) for the determination of glycogen synthase were
      performed in 15 patients before and at the end of the clamp. RESULTS: Insulin
      infusion reduced the concentrations of IGFBP-1 by 90% (P < 0.001), DHEAS by 11%
      (P < 0.001), and SHBG by 4% (P < 0.01), whereas free or bound testosterone levels
      remained unchanged. The fall in IGFBP-1 level was closely related to the basal
      concentration (r = 0.99, P < 0.001). Basal SHBG concentration correlated directly
      with total (r = 0.51, P < 0.05) and non-oxidative glucose disposal (r = 0.41, P <
      0.05), and with the decrease in lipid oxidation (r = 0.47, P < 0.05) during
      insulin infusion. The fall in SHBG was inversely related to the mean (30-240 min)
      FFA concentration during hyperinsulinaemia (r = -0.64, P < 0.001). The fractional
      activity of glycogen synthase at the end of insulin infusion correlated directly
      with fasting SHBG (r = 0.71, P < 0.01) and DHEAS concentrations (r = 0.67, P <
      0.01). CONCLUSIONS: In male type 1 diabetic patients: (1) acute hyperinsulinaemia
      decreases IGFBP-1, DHEAS and SHBG concentrations with the greatest decline in
      IGFBP-1, (2) SHBG concentration is positively associated with factors indicating
      good insulin sensitivity, (3) association between fuel homeostasis and SHBG,
      DHEAS and insulin antagonists suggests a network of these factors in the
      regulation of insulin action in type 1 diabetic patients.

PMID- 8548946
TI  - Endocrine effects of GnRH analogue with low-dose hormone replacement therapy in
      women with endometriosis.
AB  - OBJECTIVE: GnRH analogues are being used increasingly for a number of oestrogen
      dependent conditions in women. The resultant profound hypo-oestrogenism is a
      disadvantage, however, but the preservation of pituitary sensitivity to negative
      feedback by oestradiol is not well defined. We have determined the effect on
      gonadotrophins and inhibin of GnRH analogue plus low-dose continuous combined
      hormone replacement therapy in comparison with GnRH analogue therapy alone.
      DESIGN: Randomized controlled trial. PATIENTS: Fifty premenopausal women with
      endometriosis randomized to treatment with goserelin alone (Group 1) or goserelin
      plus 17 beta-oestradiol and medroxyprogesterone acetate (Group 2). MEASUREMENTS:
      FSH, LH, oestradiol, oestrone, inhibin before and during treatment. RESULTS:
      Oestradiol and oestrone were suppressed in both groups, but Group 2 had
      significantly higher oestradiol during the hormone replacement therapy period. LH
      was suppressed in both groups. In Group 1, FSH levels recovered during treatment
      but, in contrast, in Group 2, FSH levels remained suppressed throughout
      treatment. Inhibin was significantly lower in Group 2, but not in Group 1, during
      treatment compared to pretreatment. CONCLUSIONS: Pituitary secretion of FSH
      appears to remain responsive to feedback control by oestradiol during GnRH
      analogue therapy and is incompletely suppressed, unlike LH which remains
      completely suppressed. The possible mechanisms for this are discussed.

PMID- 8548947
TI  - Hexarelin induced growth hormone release is influenced by exogenous growth
      hormone.
AB  - OBJECTIVE: Growth hormone releasing peptides (GHRPs) are a group of synthetic
      compounds capable of releasing GH by an unknown mechanism. The aim of this study
      was to determine the effect of administering biosynthetic human growth hormone
      (rhGH) on the GH releasing activity of hexarelin, a new and potent GHRP, and to
      compare the results with those obtained with growth hormone releasing hormone
      (GHRH). DESIGN: Boluses of saline or rhGH were administered intravenously,
      followed 90 minutes later by a second intravenous bolus of saline, hexarelin or
      GHRH. Studies were performed following an overnight fast. Each subject underwent
      six studies performed in a random order and separated by at least 2 days.
      SUBJECTS: Six healthy adult males (23.8-34.3 years) were studied. MEASUREMENTS:
      Serum GH and IGF-I levels were measured by radioimmunoassay. RESULTS: The peak
      serum GH response to hexarelin was greater than that to GHRH, irrespective of
      whether the first bolus was saline (P < 0.05) or rhGH (P < 0.02). Prior
      administration of rhGH led to a reduction in peak serum GH response to hexarelin
      or GHRH (P < 0.05); the percentage reduction in response to hexarelin was less
      than that to GHRH, but this difference was not statistically significant (P =
      0.3). There was no change in serum IGF-I concentration before or 90 minutes after
      the administration of rhGH. CONCLUSIONS: Hexarelin is a potent GH secretagogue
      subject to partial feedback inhibition by rhGH. This raises issues about its
      mechanism of action and may have implications for its potential therapeutic use.

PMID- 8548948
TI  - Cardiovascular function and glucocorticoid replacement in patients with
      hypopituitarism.
AB  - OBJECTIVE: Retrospective analysis suggests an increased mortality from
      cardiovascular disease in hypopituitary adults; GH deficiency has been postulated
      to account for this. However, glucocorticoid replacement doses of 30 mg/day of
      hydrocortisone (HC) may be excessive, and could therefore be implicated in the
      increased cardiovascular mortality in this group of patients. The aims of this
      study were to establish whether patients with hypopituitarism have any
      abnormalities of the cardiovascular system compared to a control group and
      whether any of these parameters might be improved by reducing the replacement
      dose of glucocorticoid. PATIENTS AND MEASUREMENTS: A prospective analysis of
      cardiovascular function was carried out in 13 patients with hypopituitarism on
      routine replacement therapy and 20 normal controls who were matched for age and
      body mass index (BMI). Twenty-four-hour ambulatory blood pressure (BP), erect and
      supine BP, echocardiography, forearm plethysmography and cardiovascular reflexes
      in response to tilt, Valsalva and isometric hand grip were performed on controls
      and on patients taking 30 mg/day of HC and repeated following a reduction in HC
      dose to 15 mg/day for 3 months. Weight, plasma and urinary electrolytes, 24-hour
      urinary cortisol excretion, glucose, HbA1C and pituitary function were also
      assessed on HC 30 mg/day and 15 mg/day. RESULTS: Mean 24-hour ambulatory BP, in
      addition to day and night time BP, was lower in patients than in controls
      (achieving statistical significance in the male subgroup) and did not change
      significantly with a reduction in HC dose. Erect and supine BP was also lower in
      patients compared to controls and there was no evidence of postural hypotension
      following a reduction in HC dose to 15 mg/day. Systolic and diastolic left
      ventricular dimensions, interventricular septal thickness, ejection fraction and
      fractional shortening were similar in controls and patients and did not alter
      with a reduction in HC dose. Systolic and diastolic BP and heart rate responded
      appropriately to all tests of cardiovascular reflexes (tilt, Valsalva and
      isometric handgrip) in hypopituitary patients though again measurements of
      systolic BP were significantly lower in patients during these tests, independent
      of HC dose. Forearm plethysmography was similar in patients receiving 30 mg of HC
      and controls but forearm blood flow increased significantly when the HC dose was
      reduced to 15 mg/day. There was no change in weight, plasma and urinary
      electrolytes, glucose and HbA1C or pituitary function in the patient group
      throughout the study. CONCLUSIONS: In contrast to other studies we have failed to
      confirm cardiovascular dysfunction in GH deficient hypopituitary adults. Indeed,
      cardiovascular protection may be conferred on this group by the lower BP levels.
      Although a reduction in hydrocortisone dose was well tolerated in all patients,
      it appeared to confer no additional clinical benefit over the 3-month study
      period. In view of the conflicting data on cardiovascular function in
      hypopituitary patients, further prospective mortality studies are required in
      patients with adult GH deficiency.

PMID- 8548949
TI  - Intranasal administration of the GHRP hexarelin accelerates growth in short
      children.
AB  - OBJECTIVE: Hexarelin is a recently synthesized small growth hormone releasing
      peptide (GHRP) (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys- NH2). It is active by
      intravenous, oral and intranasal administration in animals and man. The aim of
      this study was to find out whether long-term administration of this peptide would
      promote growth in short children. DESIGN AND PATIENTS: Intranasal hexarelin was
      administered in a dose of 60 micrograms/kg thrice daily to 8 prepubertal short
      children aged 4-11.6 years for periods of up to 8 months. RESULTS: Hexarelin
      treatment stimulated insulin-like growth factor-I (IGF-I) secretion raising the
      level from 10.4 +/- 3.9 (SD) to 14.1 +/- 4.6 nmol/l (P < 0.004). The rise in IGF
      I led to a significant increase in the mean (+/- SD) linear growth velocity from
      5.3 +/- 0.8 to 8.3 +/- 1.7 cm/year (P < 0.0001). There was also a significant
      decrease in skinfold thickness despite increase in body weight and an increase in
      head circumference. Additional findings were a rise in serum phosphate from 1.5
      +/- 0.1 to 1.8 +/- 0.1 mmol/l (P < 0.004) and of alkaline phosphatase from 219 +/
      74 to 261 +/- 75 U/l (P < 0.05). CONCLUSIONS: The long-term GH/IGF-I
      stimulating, anabolic and growth promoting effects achieved by intranasal
      administration of this hexapeptide, seemingly without undesirable side-effects,
      suggests clinical potential for this new class of drugs.

PMID- 8548951
TI  - A gonadotrophin dependent stromal luteoma: a rare cause of post-menopausal
      virilization.
AB  - A stromal luteoma is an uncommon ovarian tumour in post-menopausal women, which
      presents rarely with hyperandrogenism and virilization. We present the case of a
      64-year-old woman referred for evaluation of virilization which had developed
      over 5 years. Testosterone, FSH and LH were markedly inhibited following the
      administration of a GnRH analogue, suggesting a gonadotrophin dependent,
      testosterone secreting ovarian tumour, which could not be localized with imaging
      techniques. Surgery revealed normal sized ovaries with no apparent lesions, but
      microscopic examination showed a small stromal luteoma in the right ovary and
      severe stromal hyperthecosis in the adjacent and contralateral ovarian stroma. We
      conclude that stromal luteoma is an uncommon cause of virilization in post
      menopausal women. This case illustrates, to our knowledge for the first time,
      that a stromal luteoma is not autonomous but is gonadotrophin dependent.

PMID- 8548950
TI  - Extra-adrenal effects of metyrapone include inhibition of the 11-oxoreductase
      activity of 11 beta-hydroxysteroid dehydrogenase: a model for 11-HSD I
      deficiency.
AB  - BACKGROUND AND OBJECTIVE: Previous studies suggesting effects of metyrapone on
      extra-adrenal corticosteroid metabolism have involved significant alterations in
      plasma cortisol. We have therefore studied effects of metyrapone on urinary
      excretion of steroids in a group of patients treated concurrently with
      hydrocortisone so that changes in plasma cortisol were minimized. DESIGN:
      Replacement doses of hydrocortisone (30 mg/day) were given concurrently with
      metyrapone (2-4 g/day) for 2 weeks. Blood samples were taken and 24-hour urinary
      steroid collections were made at baseline and after 1 and 2 weeks of treatment.
      PATIENTS: Subjects were 6 female patients with major depression from a trial of
      metyrapone as an antidepressant. MEASUREMENTS: Urinary steroid profiles were
      measured by gas chromatography; plasma cortisol and urinary free cortisol were
      measured by fluorescence immunoassay. RESULTS: Plasma cortisol levels were not
      significantly decreased by treatment, while excretion of 11-deoxycortisol
      metabolites increased eightfold after 2 weeks indicating that concurrent
      hydrocortisone administration had not suppressed the adrenal. Ratios reflecting
      11 beta-hydroxy/11-oxo metabolites of cortisol were significantly decreased,
      consistent with inhibition of the 11-oxoreductase activity of 11 beta
      hydroxysteroid dehydrogenase (11-HSD). Other changes included significant
      decreases in the rates of 5 alpha vs 5 beta and of 20 alpha vs 20 beta reduction
      of corticosteroids. CONCLUSIONS: Metyrapone has multiple effects on extra-adrenal
      corticosteroid metabolism and is the only agent we know of which selectively
      inhibits 11-oxoreductase. Metyrapone thus provides a model for 11-HSD I
      deficiency and a tool for in-vitro studies of cortisol-cortisone interconversion.
      The results also suggest mechanisms whereby corticosteroid effects can be
      regulated separately from corticosteroid synthesis.

PMID- 8548952
TI  - Chronic myeloid leukaemia following 131I treatment for thyroid carcinoma: a
      report of two cases and review of the literature.
AB  - Leukaemia is an uncommon late complication of exposure to the ionizing radiation
      of radioactive iodine (131I). Most cases reported have been of acute leukaemias
      developing after high doses of 131I. Only a few cases of chronic myeloid
      leukaemia (CML) have been reported in this setting to date. We report two new
      cases of CML after low dose radioactive iodine and review the literature. We
      present an analysis of the minimal relative risk of CML developing in thyroid
      cancer patients treated with 131I in Israel. Two male patients, 35 and 51 years
      old, developed CML following low dose 131I therapy for metastatic mixed papillary
      and follicular carcinoma of the thyroid. Both had undergone thyroidectomy and
      neck dissection and thyroid ablation with 131I (total dose: 56 and 130 mCi
      respectively). Four and 10 years later, respectively, a leucocytosis was noticed
      with typical blood smears, and CML was diagnosed either by Philadelphia
      translocation or bcr-abl gene rearrangement. Thyroid cancer at that time was in
      remission. Estimated minimal relative risk of CML after 131I therapy where the
      population considered at risk comprised all thyroid cancer patients detected
      during the years 1981-1991 in Israel was 8.95 (95% confidence limits 2.26-35.16).
      Literature review disclosed five additional similar cases. The mean radioiodine
      dose given to the seven CML patients was 11416MBq (range 1134-32130 MBq),
      considerably lower than the dose given to patients reported in the literature who
      subsequently developed acute leukaemias (mean 34965, range 3856-54810 MBq). We
      suggest that CML is a potential complication of low dose 131I therapy given for
      thyroid carcinoma even at the lower end of the dose range used for this
      indication. Leucocytosis appearing in these patients should raise the suspicion
      of secondary CML.

PMID- 8548953
TI  - Lipoprotein (a) changes during growth hormone treatment.

PMID- 8548954
TI  - Percutaneous tracheostomy.

PMID- 8548955
TI  - Neck dissection.

PMID- 8548956
TI  - Molecular alterations in head and neck squamous cell carcinoma.

PMID- 8548957
TI  - Posturography--applications and limitations in the management of the dizzy
      patient.

PMID- 8548958
TI  - Manometric rhinometry.
AB  - A new method of measuring nasal volume is described. It works by extracting air
      from a closed cavity and measuring the resultant pressure change. To validate
      this method in the nose, 17 healthy volunteers were examined before and after
      application of xylometazoline. The apparent volume before decongestion was a mean
      of 204 ml. After decongestion the average volume was 228 ml. The difference is
      highly significant (P < 0.01). We conclude that manometric rhinometry is a valid
      method of investigating the nose and sinuses.

PMID- 8548959
TI  - A prospective randomized controlled trial comparing the use of merocel nasal
      tampons and BIPP in the control of acute epistaxis.
AB  - A prospective study was undertaken to compare the efficacy of Merocel nasal
      tampons to BIPP (Bismuth Subnitrate and Iodoform Paste) impregnated ribbon gauze
      in the control of acute epistaxis requiring hospital admission. A total of 50
      patients presenting with severe epistaxis was treated with either merocel nasal
      tampons, or BIPP. The groups did not differ significantly in terms of age, sex
      distribution, aetiology or severity of the bleed. There was no significant
      difference in efficacy or patient tolerance of either treatment. It was concluded
      that Merocel nasal tampons should be considered effective in the first line
      treatment of severe epistaxis uncontrolled by simple measures. Their ease of
      insertion makes them suitable for use in the accident and emergency department or
      in general practice.

PMID- 8548960
TI  - Mucosal-strip/uvulectomy by the CO2 laser as a method of treating simple snoring.
AB  - The effect of stiffening the soft palate by inducing scarring after removing a
      central strip of mucosa with a CO2 laser was investigated in 25 heavy snorers.
      The results were assessed using a series of Visual Analogue Score (VAS)
      assessment questionnaires completed by the partner over a period of 6 months. Of
      the 22 patients who had the laser-strip and uvulectomy, snoring improved in 18
      (82%) (median improvement of 75% at 3 months). Four patients did not improve.
      Between 3 and 6 months, snoring increased in one patient and decreased in four (<
      10% change on VAS). Snoring did not improve in the three patients who did not
      undergo uvulectomy. We conclude that the laser-strip/uvulectomy can reduce
      snoring to a tolerable level in eight out of 10 heavy snorers, but the procedure
      is painful for several days.

PMID- 8548961
TI  - Physiological identification of the auditory nerve during surgery for acoustic
      neuroma.
AB  - We report the design and clinical use of an electrode which can locate the
      acoustic nerve fibres in the normal eighth nerve and also in eighth nerves
      deformed by acoustic neuromas. The improvement in facial nerve preservation
      during acoustic neuroma surgery is partly due to the use of a facial nerve
      stimulator to anatomically locate the fibres. Our new acoustic nerve detector has
      the capability of anatomical location of cochlear fibres which may help to
      improve hearing preservation in selected cases of acoustic neuroma. The device
      functions by detecting the compound action potential evoked by no frequency
      auditory simulation at 500 Hz. The 500 Hz compound action potential is detected
      with a bipolar probe and then amplified and filtered. This results in a 500 Hz
      tone when the probe contacts the auditory nerve. Detection is virtually
      instantaneous. The acoustic nerve detector (AND) is demonstrated in a normal
      eighth nerve complex and its use is then described in the total removal of an
      acoustic neuroma with a 1 cm extracanalicular extension in which useful hearing
      was saved post-operatively. The present prototype may not be sensitive enough to
      detect the very low signals that may result when cochlear fibres are widely
      distorted around a large tumour or in cases where slight contusion of the nerve
      occurs during dissection. In all other cases the real time anatomical information
      is extremely helpful in guiding acoustic nerve dissection and also in monitoring
      the effects of petrous bone drilling.

PMID- 8548962
TI  - Delayed endolymphatic hydrops: clinical manifestations and treatment outcome.
AB  - The clinical entity of delayed endolymphatic hydrops was first defined by
      Schuknecht in 1978. It constitutes the development of symptoms consistent with
      endolymphatic hydrops either ipsilateral or contralateral to an ear with a
      profound hearing loss. We report our experience with this condition amongst 394
      patients with Meniere's syndrome followed prospectively. Of 24 patients with the
      ipsilateral condition, nearly half responded to medical treatment. Thirteen
      patients underwent vestibular nerve section and the outcome, as assessed by a
      disability grading system, was very satisfactory. The proportion of patients
      undergoing vestibular nerve section (54.9%) was substantially higher than
      patients with classical Meniere's syndrome during the same period (5.4%)
      reflecting the increased severity of the symptoms. The contralateral form was
      less frequently seen and patients were more refractory to treatment. The
      audiological definition of delayed endolymphatic hydrops appears somewhat
      arbitrary, as these patients form a continuous spectrum with other Meniere's
      syndrome cases, occurring in association with less marked degrees of
      sensorineural hearing loss.

PMID- 8548963
TI  - Radiation-induced fibrosarcoma of the tongue.
AB  - Three patients with a radiation-induced fibrosarcoma of the tongue are presented.
      All three patients had interstitial radiotherapy and tumour-induction by
      irradiation seems to be the most likely explanation for the tumour in these
      patients.

PMID- 8548964
TI  - Allergy due to topical medications in chronic otitis externa and chronic otitis
      media.
AB  - Thirty-four patients suffering from chronic otorrhoea were tested for delayed
      type contact allergy. Patch testing showed a relevant positive reaction in 19
      patients (56%). The most frequent allergens were aminoglycosides with neomycin
      and framycetin as major offenders. Other antimicrobial agents (clioquinol,
      polymyxin B), cream bases (lanolin) and corticosteroids (tixocortol) were less
      common allergens encountered. These results indicate that it is almost obligatory
      to perform patch testing in any patient with long-standing otitis which does not
      respond to local therapy. Scoring of the patch tests has to be extended to 7
      days, as notably the aminoglycosides and corticosteroids only become positive
      after such a long interval. Because of the high risk of sensitization, topical
      preparations containing neomycin and framycetin should not be used routinely. We
      recommend the use of either a topical antiseptic or a topical antibiotic with low
      allergenic potential for the initial treatment of otorrhoea.

PMID- 8548965
TI  - Myringoplasty and tympanoplasty--results related to training and experience.
AB  - The results of surgery in a series of 452 ears having either myringoplasty (281
      ears) or tympanoplasty (171 ears) were studied in relation to the experience of
      the surgeons. The trainees received an annual course in temporal bone dissection
      and were given daily surgical instruction in the operating theatre. The 142 ears
      operated by them showed less disease than those operated upon by the programme
      chairman (114 ears) and by the faculty (196 ears). The performance of the
      trainees was safe, and as to healed tympanic membrane and hearing results all
      studied parameters were statistically equal to those of the faculty. Repair of
      anterior perforations proved to be the most difficult and the overall results of
      both the faculty and trainees left place for improvement. On-line recording of
      surgical data and annual evaluation of an individual surgeon's results is
      suggested as a necessary means for continuous post-graduate training.

PMID- 8548966
TI  - Management of subglottic haemangioma.
AB  - Between 1980 and 1993, 10 infants underwent endoscopic treatment and/or open
      surgical excision of a subglottic haemangioma. Of the eight children treated with
      the laser, four showed simple evolution following a single laser treatment, one
      required repeated laser treatments and two needed tracheotomy despite repeated
      laser treatments. The last three children developed moderate subglottic stenosis.
      Laser treatment was followed by open surgical excision in one child. Two children
      underwent primary surgical excision, allowing extubation between 8 and 10 days
      post-operatively. After a period in which we systematically treated subglottic
      haemangiomas with the laser, these findings have led us to employ open surgery in
      children with large subglottic haemangiomas or when airway obstruction requires a
      tracheostomy.

PMID- 8548968
TI  - The nasal response to isometric exercise.
AB  - The cardiovascular response to isometric exercise is well understood. However,
      the response of the nasal mucosa is less well known. We have attempted to
      document this response in normal individuals. Ten individuals with no history of
      nasal disease or allergy were studied. All subjects were asked to perform
      sustained handgrip on the side of the obstructed nostril for a period of 5 min at
      30% of maximum voluntary effort. Nasal cross-sectional area was measured on both
      sides of the nose using an acoustic rhinometer. The individuals were then rested
      for at least 30 min and the test repeated with pressure applied by the opposite
      hand. Statistical analysis was performed by non-parametric methods. There was a
      significant fall in nasal cross-sectional area on the side of exercise median
      change = 0.09 cm2, P < 0.01) while cross-sectional area in the contralateral
      nasal passage increased (median change = 0.35 cm2, P = 0.01). There was no
      significant differences between these results and those obtained by handgrip on
      the opposite side. The results indicate that isometric exercise produces nasal
      obstruction (isotonic exercise) and both afferent and efferent arms of this
      reflex are side-specific.

PMID- 8548967
TI  - A comparison of the efficacy and patient acceptability of budesonide and
      beclomethasone dipropionate aqueous nasal sprays in patients with perennial
      rhinitis.
AB  - This was an open, randomized, cross-over study comparing the efficacy and
      acceptability of aqueous nasal suspensions of budesonide, 200 micrograms b.i.d.
      and beclomethasone dipropionate (BDP), 100 micrograms q.i.d., each given for 6
      weeks to patients with perennial rhinitis and a history of allergy. Forty men and
      women aged 18-65 years with perennial rhinitis diagnosed at least 1 year
      previously, were recruited for study provided they had at least two of the
      following symptoms of rhinitis--blocked nose, runny nose, itching nose or
      sneezing. They were requested to record the presence or absence of nasal and
      ocular symptoms on a severity scale of 0-3 (none, mild, moderate, severe) in
      daily diary cards. The sum of the nasal scores was calculated to give the total
      nasal symptom score. Mean individual symptom scores and total symptom score were
      calculated for each treatment. Thirty-seven patients completed the study. The
      mean total nasal symptom score was significantly lower during budesonide (2.13)
      than during BDP (2.75), P = 0.001. There were significantly fewer reports of
      blocked nose (P = 0.004), runny nose (P = 0.0005) and sore eyes (P = 0.047)
      during budesonide treatment compared with BDP. Four patients reported adverse
      events during budesonide treatment (two had nosebleeds and two nasal dryness) and
      three patients during BDP treatment (two had nasal dryness and one gastric
      discomfort). A significantly greater proportion of patients stated a preference
      for budesonide than for BDP on the basis of effect (P = 0.0001), side-effects (P
      = 0.01), and overall (P = 0.0001).

PMID- 8548969
TI  - An acoustic screening test for obstructive sleep apnoea.
AB  - Third-octave sound analysis was performed on the snoring sounds of nine subjects
      with obstructive sleep apnoea (OSA) and 18 with simple snoring. Both groups
      demonstrated a large low frequency peak in linear sound levels at around 80 Hz.
      However, the OSA group displayed a substantially larger high frequency sound
      component. We utilized this fact in the development of an acoustic index (Hawke
      Index: HI) which describes the ratio between the overall A-weighted and linear
      sound levels for the recorded snoring sound of each subject [HI = dB(A)/dB(SPL)
      for Lmax]. There was a significant positive correlation between the
      apnoea/hypopnoea index and the HI (r = 0.73, t = 5.3, 25df, P < 0.001). If a
      value of 0.90 or greater was taken as diagnostic of OSA, the HI exhibited 67%
      sensitivity, 100% specificity, 100% positive and 86% negative predictive
      accuracy. With further development, we believe this acoustic phenomena may have a
      role as a screening test in the diagnosis of OSA.

PMID- 8548970
TI  - Long-term post-operative follow-up of patients with chronic otitis media. Does it
      make sense?
AB  - Complications ('events') encountered during long-term post-operative follow-up
      (on average, 6.5 years) of 493 patients undergoing surgery for chronic otitis
      media or its sequelae were evaluated. After the immediate post-operative period
      (of 30 days), in 44% of the patients at least one event was detected, infection
      being the most common, followed by graft failure, hearing impairment and
      recurrence of cholesteatoma. It was concluded that post-operative follow-up is
      necessary in all patients with chronic otitis media. The suitable length of
      follow-up was estimated to be 8 years for patients with cholesteatoma, 7 years
      for patients with granulating otitis media and 5 years for patients operated on
      for the sequelae of otitis.

PMID- 8548971
TI  - Resistance, humidity and temperature of the tracheal airway.
AB  - Patients after laryngectomy are subject to a high incidence of chest complaints.
      In attempting to reduce these a number of 'new nose' stoma filters have recently
      been introduced which claim to humidify and warm air, filter particulate matter
      and, by increasing tracheal airway resistance, to improve lung function. Our
      study defines the normal tracheal temperature, humidity and resistance values
      which were obtained from 16 patients with a normal upper respiratory tract. These
      parameters will allow the available filters to be evaluated objectively and may
      lead to the development of a more physiological 'new nose'.

PMID- 8548972
TI  - The use of topical 5% lignocaine ointment for the relief of pain associated with
      post-operative nasal packing.
AB  - Packing of the nasal cavity remains a common routine precautionary measure
      following septal surgery. The nasal pack and its removal 24 h later are often
      cited by patients as the most painful aspects of septal surgery. We present the
      results of a randomized, prospective controlled trial of the use of topical 5%
      lignocaine ointment as a method of pain relief following post-operative nasal
      packing. Post-operative pain as measured using a visual analogue scale at 3 h
      post-operatively was halved in patients receiving a lignocaine impregnated nasal
      pack compared with those having a standard vaseline gauze pack (P < 0.05). Pain
      scores at 6 h post-operatively and at pack removal were also reduced, but these
      failed to reach significance. No patients suffered reactionary haemorrhage. The
      use of topical lignocaine ointment is safe and may have a place in the relief of
      pain due to post-operative nasal packing.

PMID- 8548973
TI  - Observation of the mechanism of snoring using sleep nasendoscopy.
AB  - We have performed sleep nasendoscopy on 54 adult snorers in whom obstructive
      sleep apnoea had been excluded by an overnight sleep study. The purpose of the
      study was to identify the site or sites of noise production in each case. This
      was successfully achieved in 50 of the 54 and 70% showed palatal flutter snoring
      only. In a further 20%, palatal flutter snoring was combined with evidence of
      noise generation at another site. The second site was supraglottic in 10%,
      tonsillar in 8% and tongue base in 2%. The tongue base was also the sole site of
      noise generation in 8% and the epiglottis was the sole site in 2%. This study
      suggests that sleep nasendoscopy can identify different mechanisms of snoring in
      individual patients. This information is likely to be of use in formulating a
      logical surgical treatment plan.

PMID- 8548974
TI  - Histological fate of cortical bone autografts in the middle ear.
AB  - Histological studies have been carried out on six cortical bone autografts and
      three ossicular grafts removed between 6 and 232 months after implantation in
      ossicular reconstructions. Both types of graft consisted mainly of dead bone,
      with some areas of viable osteocytes. Four out of six cortical bone grafts showed
      evidence of new bone formation and only one had reduced in size during the period
      in the middle ear. Fibrosis and inflammation were also noted in some specimens.
      In most cases cortical bone autografts appear to survive as well as ossicular
      grafts in the middle ear.

PMID- 8548975
TI  - Assessment of early- and late-phase nasal obstruction in atopic patients after
      nasal allergen challenge.
AB  - In order to study the types of nasal obstruction in allergic rhinitis, nasal
      allergen challenge was performed in 18 atopic patients, compared with a control
      group consisting of 10 healthy volunteers. Passive anterior rhinomanometry was
      used as an objective evaluation of nasal airway resistance. A 100% increase of
      nasal airway resistance was considered to be a positive reaction. In the control
      group, no obvious nasal obstruction was recorded after nasal phosphate buffered
      saline challenge. In the patient group, nasal obstruction occurred only after
      challenge in 94% during the early phase and in 82% during the late phase. During
      the late-phase four major types of nasal obstruction were found, i.e. no nasal
      obstruction; one-sided nasal obstruction only; bilateral nasal obstruction; and
      alternating nasal obstruction. Of the four types, the alternating type was the
      most common (47%) type, especially during the late-phase.

PMID- 8548976
TI  - Mucormycosis: experience with 10 patients.
AB  - Rhinocerebral mucormycosis is a fulminating, devastating fungal disease, usually
      associated with debilitating diseases such as diabetes mellitus, leukaemia and
      immunosuppressive conditions. Ten patients with this rare disease have been
      treated over the past 14 years at the Beilinson Medical Centre. Nine patients had
      an underlying debilitating disease and one patient had latent diabetes mellitus
      which was diagnosed only after presentation of mucormycosis. Only two of the 10
      patients survived. Early aggressive surgical debridement, together with
      amphotericin B and correction of underlying metabolic acidosis were found to be
      important factors associated with survival.

PMID- 8548977
TI  - Ambulatory esophageal manometry in the evaluation of unexplained chest pain.

PMID- 8548978
TI  - Ambulatory esophageal manometry in the evaluation of unexplained chest pain.
AB  - Ambulatory esophageal manometry is a relatively new technology, widely accepted
      as a research tool in the study of esophageal motility disorders. Its role as a
      clinical tool has been more controversial. This paper reviews current opinions
      regarding the use of this diagnostic tool, and attempts to summarize the
      advantages and shortcomings of this technology as it has been employed in the
      evaluation of unexplained chest pain.

PMID- 8548979
TI  - Transjugular intrahepatic portosystemic shunt: a medical perspective.
AB  - The transjugular intrahepatic portosystemic shunt (TIPS) is an exciting new
      addition to the therapeutic armamentarium against portal hypertension. It is
      currently indicated for salvage of patients with active variceal hemorrhage
      despite sclerotherapy or where sclerotherapy is not feasible. Its use for
      recurrent episodes of bleeding despite chronic sclerotherapy and for ascites and
      hepatorenal syndrome remains experimental. It is contraindicated in patients with
      right-heart failure and portal vein thrombosis. TIPS is not indicated for primary
      prophylaxis of variceal hemorrhage or portal decompression prior to liver
      transplantation. TIPS is associated with its unique spectrum of complications
      which can occasionally be life-threatening. Although initial experience with this
      procedure is encouraging, a great amount of work remains to be done to fully
      define its role in clinical practice.

PMID- 8548980
TI  - Chronic intestinal pseudo-obstruction.
AB  - Chronic intestinal pseudo-obstruction denotes the clinical picture that results
      due to the failure of intestinal peristalsis to overcome the normal resistance to
      flow and is characterized by recurrent episodes of signs and symptoms of
      intestinal obstruction in the absence of any mechanical compromise of the
      intestinal lumen. The region(s) of the gut affected may be isolated or diffuse.
      It is not uncommon to find evidence of autonomic neuropathy and smooth muscle
      dysfunction with extraintestinal manifestations such as urinary symptoms from
      abnormal ureter or bladder function. Intestinal pseudo-obstruction can be caused
      by a variety of diseases, and for simplicity, certain authors have divided it
      into myopathic and neuropathic categories. Intestinal pseudo-obstruction may
      present at any age with a variable amount of abdominal pain, distension, nausea,
      diarrhea, or constipation and with laboratory abnormalities usually reflecting
      the degree of malabsorption and malnutrition present. The radiologic findings are
      varied but commonly include paralytic ileus or signs of apparent clinical
      obstruction with dilated loops of bowel. The number of pseudo-obstruction cases
      is dependent on how one defines the condition. It appears prudent to require
      radiographic abnormalities consistent with obstruction on a plain film of the
      abdomen for the diagnosis. More recently, studies have focused on the
      gastrointestinal manometric abnormalities of the stomach and small intestine in
      chronic intestinal pseudo-obstruction during fasting and fed states; however,
      sensitivity and specificity of these abnormalities are not well defined.
      Treatment is aimed at limiting symptoms and maintaining adequate nutrition.
      Prokinetic agents should be tried in an attempt to restore normal intestinal
      propulsion. However, their overall efficacy appears to be variable. It is still
      too premature to consider intestinal pacing or small bowel transplantation in
      this condition. Surgical approaches to chronic intestinal pseudo-obstruction
      should be limited to patients refractory to medical therapy, and even then, an
      approach focused on the patient's primary presenting symptoms should be
      considered.

PMID- 8548981
TI  - Molecular biology and colorectal cancer: genetic alterations, inherited
      syndromes, and applications to colon cancer screening.
AB  - Molecular genetics has rapidly advanced our understanding of pathogenesis and
      biologic behavior of colorectal carcinoma. This article will review the genetic
      changes which occur in colonic mucosa as it progresses from benign to malignant
      as well as review the inherited forms of colorectal cancer. Current screening
      methods and anticipated future strategies for colorectal cancer screening will be
      discussed.

PMID- 8548982
TI  - Cholera in the United States.
AB  - Cholera remains a threat to human health in many parts of the world, including
      the United States. The epidemiology of cholera is reviewed to prepare for
      identification and prevention of the disease in appropriate clinical settings.
      The clinical manifestations of cholera and the pathophysiology of the toxin
      induced diarrhea are reviewed to introduce and to clarify appropriate therapeutic
      and preventive interventions.

PMID- 8548983
TI  - Fulminant hepatic failure secondary to previously unrecognized cardiomyopathy.
AB  - Fulminant hepatic failure is infrequently seen as a consequence of acute
      congestive heart failure. Recognition of this entity is important as treatment
      directed towards heart failure should help resolve the liver failure. A case of
      fulminant hepatic failure due to previously unrecognized cardiomyopathy is
      presented. A liver transplantation was being considered for fulminant hepatic
      failure until hemodynamic monitoring studies demonstrated that, in fact, the
      patient had severe cardiomyopathy. Treatment directed at his cardiomyopathy
      resolved the liver failure. Therefore, prompt recognition of such a phenomenon
      would enable early institution of appropriate therapeutic measures with the hope
      of clinical benefit to the patient.

PMID- 8548984
TI  - Management of the immunobullous disorders. II. Pemphigus.
AB  - In the second of our reviews on the management of the immunobullous disorders, we
      review the therapy of pemphigus disorders, including pemphigus vulgaris,
      pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, pemphigus
      herpetiformis, drug-induced pemphigus, IgA pemphigus and paraneoplastic
      pemphigus.

PMID- 8548985
TI  - Uraemic pruritus is not related to plasma histamine concentrations.
AB  - Pruritus is a common symptom in uraemic patients and its aetiology is poorly
      understood, although several factors have been implicated, including high
      histamine plasma levels. The aim of the study was to evaluate plasma levels of
      histamine in patients on maintenance haemodialysis in relation to the presence of
      itching (35 pruritic patients = group A; 50 non-pruritic patients = group B).
      Furthermore, we compared the values obtained with those of a healthy control
      group (64 subjects). We observed increased plasma histamine levels in uraemic
      patients compared with healthy controls. However, no relationship was found
      between plasma histamine values and itching because groups A and B showed
      overlapping values and there was no correlation between the intensity of pruritus
      and plasma histamine concentrations in group A patients. In conclusion, we
      suggest that there is no evidence for plasma histamine playing a significant part
      in uraemic pruritus.

PMID- 8548987
TI  - Increase in non-melanoma skin cancer--the King's College Hospital experience
      (1970-92).
AB  - A retrospective study of the number of patients with non-melanoma skin cancer
      treated over a 22-year period at King's College Hospital was carried out. There
      was a threefold rise in the number of patients with basal cell carcinoma and a 10
      fold rise in the number of patients with squamous cell carcinoma from 1970 to
      1992. This study demonstrates a marked increase in the number of patients with
      non-melanoma skin cancers presenting to the Department of Dermatology and
      reflects a national trend which underlines the need for skin cancer services to
      be prepared for a growing workload in this area.

PMID- 8548986
TI  - Polymorphic light eruption--an immunopathological study of provoked lesions.
AB  - Polymorphic light eruption (PLE) lesions were induced in 26 patients after an
      average of 60 J total body UVA irradiation. Using the criteria of the French
      literature, that make a distinction between PLE and benign summer light eruption
      (BSLE), the group of 26 patients with PLE was divided into 12 patients with BSLE
      and 14 patients with PLE, on the basis of historical criteria. Biopsies were
      taken and compared immunohistochemically with biopsies from 15 unirradiated
      normal control subjects, in order to find evidence in support of the hypothesis
      that PLE involves a delayed-type hypersensitivity reaction. The provoked lesions
      showed: ICAM-1 expression on the keratinocytes of the basal and suprabasal cell
      layers in 18 of 25 patients, i.e. 72%; HLA-DR expression on the keratinocytes of
      the basal, squamous and granular cell layer in 13 of 25 patients, i.e. 52%; and
      OKM5 expression on the keratinocytes of the granular cell layer in 13 of 26
      patients, i.e. 50% of the cases. The control samples showed no such antigen
      expression on the keratinocytes, except for two cases where weak and very
      localized ICAM-1 positivity was observed; one of these also had a slight
      localized positivity for HLA-DR and OKM5. The results of the phototesting
      procedures and the immunohistochemical investigations were similar in both BSLE
      and PLE. This suggests that they are the same condition, and the term BSLE should
      therefore probably be discarded. The results of our investigations support the
      theory of an immunological basis for PLE.

PMID- 8548988
TI  - A computerized analysis of intrinsic forces in the skin.
AB  - The skin of the volar forearm is a site selected for many biometrological
      studies. We studied the influence of forearm position when evaluating the surface
      topography and mechanical properties of the skin in normal young adults. Optical
      profilometry of skin replicas and the suction biomechanical method (Cutometer, 2
      and 8 mm probes) were used in combination with evaluation of the thickness and
      sliding mobility of the dermis and dermohypodermal tissues. The dermal and
      dermohypodermal thicknesses did not correlate with the various profilometric and
      biomechanical measurements. The surface topography and the axial sliding mobility
      of the skin were markedly influenced by forearm position, while the only
      mechanical property of the skin to be affected was skin stretchability assessed
      with the 2 mm probe. It is concluded that limb position mostly influences
      biometrological measurements made in the plane of the skin surface, while it has
      little effect on most of the Cutometer measurements.

PMID- 8548989
TI  - The growth of ichthyotic epidermal cells in a 3-dimensional reconstruction of
      human skin, the skin equivalent.
AB  - We have studied the differentiation of ichthyotic epidermis in vitro using the
      skin equivalent model. The morphology of these ichthyotic cultures has been
      investigated using histopathological and histometric techniques including
      epidermal and stratum corneum thickness measurements. The skin equivalents have
      also been investigated for the presence of markers of differentiation using
      immunolocalization techniques. These markers include the 65.5 and 67 kDa
      keratins, desmoplakin, involucrin, laminin and filaggrin. It has been shown that
      the ichthyotic epidermis develops a fully differentiated epidermis and stratum
      corneum, equivalent to those seen in normal skin equivalents.

PMID- 8548990
TI  - Partial unilateral lentiginosis: report of seven cases and review of the
      literature.
AB  - Partial unilateral lentiginosis is a rare disorder of cutaneous pigmentation
      characterized by the presence of multiple lesions of simple lentigo involving,
      wholly or partially, one half of the body. We report seven cases of this
      condition.

PMID- 8548991
TI  - Multiple hidrocystoma of the face: three cases.
AB  - Multiple hidrocystomas of the face (Robinson type) is an uncommon variant of
      hidrocystoma consisting of multiple cysts of the face of middle-aged women with
      exacerbation in hot temperatures. Controversy about the eccrine or apocrine
      nature of these lesions has appeared in the literature almost since their
      original description in 1893. Immunohistochemistry is not helpful in
      distinguishing between eccrine and apocrine differentiation in these lesions and
      enzyme histochemical studies have not been conclusive. We report three patients
      with this rare variant of hidrocystoma. In our opinion, multiple hidrocystomas of
      the face are apocrine hidrocystomas in which characteristic 'decapitation'
      secretion has been effaced by the pressure of cyst contents against the lining
      epithelium; only after serial sections is it possible to identify some areas of
      the cyst lining showing apocrine secretion in the luminal border of columnar
      cells.

PMID- 8548992
TI  - Multiple pilosebaceous cysts.
AB  - We report two patients initially diagnosed as having steatocystoma multiplex
      (SM). Other cysts showed characteristics of eruptive vellus hair cyst (EVHC).
      More than 30 and 14 cysts, respectively, were removed with histological hybrid
      characteristics of SM and EVHC. This suggests that SM and EVCH are two closely
      related entities, which represent a naevoid malformation in the area where the
      sebaceous duct and hair follicle meet.

PMID- 8548993
TI  - Reticular pigmented genodermatosis with milia--a special form of Naegeli
      Franceschetti-Jadassohn syndrome or a new entity?
AB  - A 19-year-old woman with a condition since birth, comprising reticular
      hyperpigmentation, palmoplantar hyperkeratosis, dental anomalies, hypoplasia of
      dermatoglyphics and a slight yellowish hue to the nails is presented. Her father
      and grandfather were similarly affected. The reticular hyperpigmentation,
      although generalized, was more intense on the flexural areas where extensive
      milia formation was also observed. This case represents an unusual
      genodermatosis. The milia formation and the presence of normal perspiration
      indicate a special form of Naegeli-Franceschetti-Jadassohn (NFJ) syndrome, or a
      new entity close to the NFJ syndrome. The differential diagnosis from other
      congenital reticulate pigmentary disorders is discussed.

PMID- 8548994
TI  - Familial lichen nitidus.
AB  - I report familial lichen nitidus in a 33-year-old father and his 3-year-old
      daughter. Histopathology of small papules in both cases revealed typical features
      of lichen nitidus. Immunohistochemical examination showed UCHL1-positive, L-26
      negative lymphocytes and HAM56-positive histiocytes and multinucleated giant
      cells in the dermal infiltrate in both cases.

PMID- 8548995
TI  - Selective fixed drug eruption to amoxycillin.
AB  - A selective fixed drug eruption to amoxycillin but not other betalactam drugs is
      reported. Penicillins are the drugs most frequently implicated in immunological
      adverse reactions. The most important of these are allergic reactions where an
      IgE-mediated mechanism is well established. Other immunological mechanisms have
      been described in reactions, such as haemolytic anaemia, serum sickness, drug
      induced nephritis, drug fever and contact dermatitis. Fixed drug eruption (FDE)
      is a type of drug-induced dermatosis, the immunopathogenesis of which remains
      unknown. FDE is an uncommon reaction to penicillin derivatives, and very few
      cases have been reported. We present a case of a selective FDE to amoxycillin
      (AX), with no reaction to other betalactam drugs. Although one similar case has
      been reported, the reactivity to other penicillin derivatives was not assessed.

PMID- 8548996
TI  - Diltiazem-induced acute generalised exanthematous pustulosis.
AB  - Pustulation is a major feature in several different dermatoses, and it may also
      occur as a manifestation of drug hypersensitivity. Acute generalized
      exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute,
      extensive formation of sterile pustules, fever and peripheral blood leucocytosis.
      It shares several clinical and histological features in common with pustular
      psoriasis. Most reported cases have been triggered by ingestion of broad spectrum
      antibiotics, particularly betalactams and macrolides. There is usually rapid
      resolution of the eruption on drug withdrawal. We report the case of a 58 year
      old woman who developed AGEP shortly after commencing treatment with the calcium
      channel blocker diltiazem hydrochloride. The eruption followed a biphasic course,
      and improved following treatment with systemic corticosteroids and methotrexate.
      AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide
      range of other skin eruptions have been reported more commonly with this drug.

PMID- 8548997
TI  - ANCA-associated vasculitis and lupus-like syndrome caused by methimazole.
AB  - A 24-year-old woman with Graves' disease treated with methimazole for 4 years,
      developed recalcitrant ulcers on the lower legs. Histological studies
      demonstrated vasculitis in deep dermal vessels accompanied by C3 deposition.
      Laboratory investigation revealed lupus-like abnormalities (leucocytopenia,
      positive antinuclear and antidouble strand (ds) DNA antibodies, and positive
      ANCA). The leg ulcers dramatically improved after methimazole was withdrawn. In
      addition, leucocytopenia and the immunological abnormalities soon faded. Although
      lupus-like syndrome is well known to be induced by antithyroid drugs, vasculitis
      is a rare complication. To the best of our knowledge, this is the first report
      describing ANCA-associated vasculitis caused by methimazole.

PMID- 8548998
TI  - Massive isotretinoin intoxication.
AB  - We report a case of acute intoxication due to a massive overdose of isotretinoin.
      A 29-year-old male patient ingested 900 mg of isotretinoin corresponding to 12.5
      mg (kg/day) or 30 times the prescribed dosage and 1 day later the patient
      experienced mild headache. Forty-eight hours later, cheilitis, diffuse cutaneous
      xerosis and desquamation of the forehead and of the external auditory meatus
      occurred; cutaneous xerosis and cheilitis resolved spontaneously, We determined
      the serum level of isotretinoin and of 4-oxo-isotretinoin, its natural metabolite
      in sera taken 4, 5, 6 and 11 days following ingestion. The side-effects were mild
      and represented only exacerbations of some common isotretinoin side-effects. To
      date, three other cases of isotretinoin overdosage have been reported. There was
      a low toxicity of isotretinoin overdose.

PMID- 8548999
TI  - Chronic angio-oedema of the tongue associated with pernicious anaemia and
      Hashimoto's thyroiditis.
AB  - The cause of chronic urticaria and angio-oedema (CUA) often remains undetermined.
      CUA has been associated with thyroid disease and most recently with thyroid
      autoimmunity (i.e. elevated titres of thyroid microsomal and/or thyroglobulin
      antibody). There is growing speculation that in this subset of patients, CUA may
      represent an autoimmune phenomenon. We describe a case in which chronic angio
      oedema of the tongue was the sole presenting complaint in a patient with
      underlying quiescent pernicious anaemia and Hashimoto's thyroiditis. Awareness of
      the association of Hashimoto's thyroiditis with pernicious anaemia and CUA
      resulted in correct diagnosis and treatment of the underlying diseases.

PMID- 8549000
TI  - Azathioprine hypersensitivity-like reactions--a case report and a review of the
      literature.
AB  - Azathioprine is used in a variety of dermatological conditions. However, because
      of its side-effect profile, azathioprine is limited for use in patients with
      severe disease. An unpredictable, rare and potentially fatal side-effect of
      azathioprine is the development of a hypersensitivity reaction, often consisting
      of fever, hypotension and oliguria. We describe a 17-year-old patient with
      leucocytoclastic vasculitis who was placed on azathioprine; within 15 days of
      start of therapy, she developed a fever. Azathioprine was discontinued and an
      evaluation for sepsis was undertaken; all cultures were negative and the fever
      abated. Azathioprine was restarted 5 days later. After a single dose, fever,
      nausea and vomiting, diarrhoea, hypotension, tachycardia and oliguria developed
      and the patient was admitted to an intensive care unit. Azathioprine was
      discontinued and investigations revealed no sign of an infection. All the above
      signs and symptoms abated within 24 h and the patient was discharged from
      hospital in 7 days. A review of 28 case reports in the literature of azathioprine
      induced hypersensitivity reactions suggest that most commonly a fever and
      gastrointestinal symptoms occurred on initial presentation. In addition, a
      maculopapular rash, urticaria, vasculitis, erythema multiforme or erythema
      nodosum may occur. Hepatotoxicity and nephritis have also been reported. The
      aetiology of the reaction is unknown but sudden onset of fever and hypotension
      suggests that this reaction may be due to cytokine or mediator release induced by
      azathioprine. As azathioprine is metabolized to 6-MP, rechallenges to both should
      be avoided in patients who experienced an azathioprine hypersensitivity-like
      reaction.

PMID- 8549002
TI  - Acquired scrotal lymphangiomata.

PMID- 8549001
TI  - Invasive periorbital squamous cell carcinoma.

PMID- 8549003
TI  - Beau's lines in immunobullous disease.

PMID- 8549004
TI  - Bullous pemphigoid following radiotherapy.

PMID- 8549005
TI  - Bullous pemphigoid following radiotherapy.

PMID- 8549006
TI  - Symposium: Diabetes Update... New Developments in Pathophysiology and Treatment
      of NIDDM. Vancouver, British Columbia, Canada, October 15-16, 1994.

PMID- 8549007
TI  - Epidemiologic studies on the pathogenesis of non-insulin-dependent diabetes
      mellitus (NIDDM).
AB  - The diagnostic criteria of the US National Diabetes Data Group and the World
      Health Organization have stimulated a major increase throughout the world in
      epidemiologic studies on the pathogenesis of non-insulin-dependent diabetes
      mellitus (NIDDM). They have established that much of NIDDM is undiagnosed, that
      onset of NIDDM occurs at least 7 y before its diagnosis, and that significant
      morbidity and premature mortality occur in subjects with undiagnosed diabetes.
      New studies have shown that rural or traditional-living populations are
      experiencing a major increase in the burden of NIDDM as they move to urban or
      nontraditional situations, often with 5- to 10-fold increases in NIDDM
      prevalence. Epidemiologic studies have documented that major risk factors for
      NIDDM include increasing age, greater obesity, longer duration of obesity,
      unfavourable body fat distribution, physical inactivity, and hyperinsulinemia.
      All these factors interact with unknown genetic factors to produce NIDDM. Studies
      have shown that genes for diabetes, as yet undetermined, are a necessary cause of
      NIDDM. Hyperinsulinemia exists in childhood in populations at high risk for
      NIDDM. Stimulated by obesity, upper body obesity, and physical inactivity,
      insulin resistance develops, accompanied by impaired glucose tolerance. The
      pressure of the NIDDM risk factors continues this process of insulin
      resistance/hyperinsulinemia/hyperglycemia, until glucose toxicity to the beta
      cell results in inability to secrete sufficient insulin, resulting in
      decompensated fasting hyperglycemia.

PMID- 8549008
TI  - Epidemiology of diabetes mellitus in Canada.
AB  - We present data on 5 aspects of the epidemiology of diabetes mellitus in Canada:
      (a) the incidence of insulin-dependent diabetes mellitus in those under 15 years
      of age. The 2 Canadian centres that participated in the Diabetes Epidemiology
      Research International study had different incidence rates in IDDM:25.5/100,000
      in Prince Edward Island (PEI) and 9.2/100,000 in Montreal. The reasons for this
      difference are not yet established. Studies on incidence of IDDM over a decade in
      PEI showed an apparent epidemic of the disease; (b) the prevalence of self
      reported diabetes mellitus in Canadian adults. The overall prevalence of self
      reported diabetes in Canadian adults (18-74 y) was 5.1% in the Canadian Heart
      Health Survey. There were no significant regional differences in prevalence of
      diabetes across Canada. The prevalence rates increased with age; (c) mortality
      data in people with diabetes mellitus. In PEI, 321 persons with diabetes died
      between January 1, 1982 and December 31, 1984, accounting for about 2% of all
      deaths. Diabetes was listed as the underlying cause in 16.8% of the deaths, as a
      contributing cause of death in 41.7%, and not mentioned at all in 41.1% of the
      deaths. Irrespective of whether diabetes was mentioned or not, myocardial
      infarction and cerebral vascular disease were the 2 major causes of deaths in
      these 321 persons with diabetes; (d) the prevalence of cardiovascular risk
      factors in Canadian adults with diabetes mellitus. In the Canadian Heart Health
      Survey, the prevalence rates of obesity, hypertension, sedentary lifestyle, and
      hypercholesterolemia were higher in the diabetic group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8549009
TI  - The key role of islet dysfunction in type II diabetes mellitus.
AB  - Fasting plasma glucose levels are constant from day to day in normal individuals.
      This constancy is due to a close co-ordination between glucose production by the
      liver and glucose uptake in peripheral tissues. This review focusses on the key
      role of the endocrine pancreas alpha- and beta-cells to provide this co
      ordination. Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by
      fasting hyperglycemia. The degree of fasting hyperglycemia, in turn, is
      correlated with the basal rate of hepatic glucose production. This increased rate
      of glucose release by the liver results in part from impaired hepatic sensitivity
      to insulin, but is largely due to reduced insulin secretion and increased
      glucagon secretion. Though basal immunoreactive insulin and glucagon levels in
      patients with NIDDM may appear normal when compared to those of healthy
      individuals, islet function testing at matched glucose levels reveals impairments
      of basal, steady-state, and stimulated insulin and glucagon secretion due to a
      reduction in beta-cell secretory capacity and a reduced ability of glucose to
      suppress glucagon release. The degree of impaired beta-cell responsiveness to
      glucose is closely related to the degree of fasting hyperglycemia, but in a
      curvilinear fashion. Thus, islet alpha- and beta-cell function is reduced by more
      than 50% in NIDDM by the time that clinical fasting hyperglycemia develops (140
      mg/dL). The efficiency of glucose uptake by the peripheral tissues is also
      impaired due to a combination of decreased insulin secretion and defective
      cellular insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549010
TI  - Glucose toxicity: the implications of hyperglycemia in the pathophysiology of
      diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) results from a disruption of
      normal glucose homeostasis, primarily insulin secretion and hepatic and
      peripheral insulin action. However, chronic hyperglycemia has been shown in
      animal models to contribute to impaired insulin secretion as well as to
      peripheral insulin resistance. Consequently, stringent control measures aimed at
      ameliorating chronically elevated blood glucose levels may help lessen the
      cellular "toxic" effect of hyperglycemia.

PMID- 8549011
TI  - Hyperinsulinemia and atherosclerosis.
AB  - Studies of macrovascular disease in non-insulin-dependent diabetes (NIDDM) have
      shown a significant increase in peripheral vascular, coronary, and carotid artery
      disease in diabetics compared to non-diabetics. This prevalence appears to be
      related to insulin levels and to the degree of hyperinsulinemia as measured in
      the blood of these patients. Indeed, a cluster of markers, including
      hyperinsulinemia, insulin resistance, hypertension, dyslipoproteinemia, and a
      high waist-hip ratio, has been associated with NIDDM and increased risk for
      macrovascular disease. Variously described as Metabolic Syndrome or Syndrome X,
      this syndrome may be operative for many years before NIDDM is diagnosed. Given
      the complexity of Metabolic Syndrome, a single-factor intervention for preventing
      macrovascular disease in NIDDM is unlikely. However, it seems advisable to
      screen, on a regular basis, all patients presenting a pre-NIDDM state, as well as
      those with overt NIDDM, for pertinent cardiovascular risk parameters and for
      emerging macrovascular disease. It is suggested that any attempt to prevent
      macrovascular disease in subjects with glucose intolerance should aim at
      decreasing insulin resistance and hyperinsulinemia.

PMID- 8549012
TI  - Biochemical and vascular factors in the pathogenesis of diabetic neuropathy.
AB  - The reasons humans develop diabetic neuropathy are not known. It seems likely
      that, as in animals, the polyol-myoinositol-aldose reductase controlled pathways
      are relevant at an early stage and are related to hyperglycemia. Perhaps these
      metabolic factors influence the structural and dynamic aspects of the
      microvasculature which are so clearly abnormal in established diabetic
      neuropathy. A demonstration that these metabolic factors in some way affect the
      vasculature would be important, for that would allow some logic in administering
      inhibitors to prevent vessel changes of such a pathological nature. At the
      moment, the case for the long-term administration of aldose reductase inhibitors
      to prevent nerve damage is not proven, and the decision to administer them will
      cause some difficulty to physicians. Unfortunately, the situation is more complex
      than this simple aldose reductase-microvascular hypothesis, for consideration
      must be given to the known glycation of nerve proteins, the involvement of fatty
      acid metabolism within the vasculature, and the undoubted role of growth factors.

PMID- 8549013
TI  - The pathological implications of protein glycation.
AB  - Hyperglycemia, the most obvious metabolic abnormality in diabetes, is the primary
      casual factor responsible for the development of diabetic microvascular
      complications. There is considerable evidence linking hyperglycemia with the
      accelerated formation of irreversible nonenzymatic advanced glycosylation end
      products (AGEs), which subsequently accumulate in vessel wall proteins. The
      development of long-term vascular complications associated with diabetes appears
      to be related to the accumulation of these AGEs. Compounds that inhibit the
      development of AGE formation prevent complications in animal models and,
      therefore, may prove useful in reducing chronic diabetes-related complications in
      patients.

PMID- 8549014
TI  - Dyslipoproteinemias in diabetes.
AB  - The risk of macrovascular disease in those with diabetes is several-fold greater
      than that in the general population. One of the many groups of factors that might
      contribute to this is the dyslipoproteinemias. Among the dyslipoproteinemias in
      diabetes, the most frequently observed abnormality is hypertriglyceridemia.
      Levels of low-density lipoprotein (LDL) and of plasma cholesterol in those with
      diabetes are similar to those observed in people without diabetes. However, in
      diabetes there may be qualitative modifications in LDL (as well as in other
      lipoproteins) that increase their atherogenicity. At present there is one study,
      the Diabetes Atherosclerosis Intervention Study (DAIS), specifically designed to
      examine whether correcting the dyslipoproteinemia of diabetes will reduce the
      angiographic progression of coronary artery disease. Until results are available
      from studies that are designed to investigate the lipid hypothesis in those with
      diabetes, recommendations for the treatment of dyslipoproteinemias in diabetes
      will be based on pathophysiologic reasoning and on extrapolation from
      interventions studies conducted in nondiabetic individuals.

PMID- 8549015
TI  - Traditional pharmacological management of non-insulin-dependent diabetes.
AB  - Most traditional hypoglycemic treatments for non-insulin-dependent diabetes
      mellitus (NIDDM) are of considerable antiquity. What we would now call a low
      carbohydrate diet was first used in 1796; insulin was introduced in 1922; the
      (toxic) biguanide synthalin was used sparingly from 1926 until the Second World
      War; and tolbutamide and chlorpropamide were marketed in the late 1950s.
      Amphetamine was available as an anorectic agent in the 1950s. Hence,
      representatives of all our present treatments for NIDDM have been available for
      over 30 y, but there is still great uncertainty about how to use them best. This
      uncertainty is reflected in major variations in prescription rates from country
      to country. In spite of this formidable pharmacological armamentarium, we have to
      face the fact that glycemic control is unsatisfactory in the majority of patients
      with NIDDM; irrespective of the mode of treatment, less than a quarter have a
      normal glycated hemoglobin. We clearly need new approaches to control glycemia in
      NIDDM. Furthermore, in addition to high blood glucose, many patients with NIDDM
      also have hypertension, hyperlipidemia, and other atherogenic abnormalities that
      need to be tackled if mortality (predominantly from atherosclerotic vascular
      disease) is to be reduced. It seems improbable that a single drug will be found
      to cure the many metabolic abnormalities. Polypharmacy thus seems inevitable for
      many patients.

PMID- 8549016
TI  - Implications of altering the rate of carbohydrate absorption from the
      gastrointestinal tract.
AB  - The rate of absorption of carbohydrate from the small intestine plays a major
      role in determining the metabolic effects of dietary carbohydrate. Factors which
      reduce the rate of absorption include the nature of the starch and sugars, and
      the presence of vegetable proteins, fats, viscous fibre, and antinutrients,
      including lectins and phytates. The rate of absorption can also be manipulated by
      the use of specific enzyme inhibitors and by increasing the number and frequency
      of meals while holding caloric intake constant. All these factors contribute to
      the creation of what may be termed slow release or "lente carbohydrate". The
      slowing of small intestinal absorption, as exemplified by increased meal
      frequency ("nibbling"), results in reduced postprandial insulin secretion and
      lower low-density lipoprotein (LDL) cholesterol and apolipoprotein B
      concentrations. A further effect of some manipulations which reduce the rate of
      absorption is increased delivery of carbohydrate to the colon and its absorption
      after bacterial fermentation to short-chain fatty acids (SCFA). These SCFA may
      have beneficial effects on colonic health(butyrate) or further inhibit
      cholesterol synthesis in the liver (propionate). Thus the absorption of "lente
      carbohydrate" takes place along the full length of the gastrointestinal tract
      with a wide variety of physiological consequences.

PMID- 8549017
TI  - The mechanism of alpha-glucosidase inhibition in the management of diabetes.
AB  - The development of the alpha-glucosidase inhibitor acarbose provides a new
      approach in the management of diabetes. By competitive and reversible inhibition
      of intestinal alpha-glucosidases, acarbose delays carbohydrate digestion,
      prolongs the overall carbohydrate digestion time, and thus reduces the rate of
      glucose absorption. After oral administration of acarbose, the postprandial rise
      in blood glucose is dose-dependently decreased, and glucose-induced insulin
      secretion is attenuated. Because of diminished postprandial hyperglycemia and
      hyper-insulinemia by acarbose, the triglyceride uptake into adipose tissue,
      hepatic lipogenesis, and triglyceride content are reduced. Therefore, acarbose
      treatment not only flattens postprandial glycemia, due to the primary and
      secondary pharmacodynamic effects, but also ameliorates the metabolic state in
      general. In diabetic animals, acarbose reduced urinary glucose loss, the blood
      glucose area under the curve, and prevented the decrease in skeletal muscle GLUT4
      glucose transporters. As a consequence of the reduced mean blood glucose area
      under the curve, the amount of protein nonenzymatically glycated was diminished,
      as was the formation of advanced glycation end-products (AGEs). The prevention of
      basement membrane glycation and thickening in various tissues indicated that
      acarbose treatment of diabetic animals produced beneficial effects against the
      development of nephropathy, neuropathy, and retinopathy. Thus, the alpha
      glucosidase inhibitor acarbose may have the potential to delay or possibly
      prevent the development of diabetic complications.

PMID- 8549018
TI  - Clinical experience with acarbose as first line therapy in NIDDM.
AB  - The treatment of non-insulin-dependent diabetes mellitus (NIDDM) is based on
      dietary and oral hypoglycemic therapy. Present therapy includes diet and
      exercise, sulfonylureas, biguanides, and, if these measures fail, incremental
      doses of insulin. Current therapeutic strategies include the combination of
      different agents in an attempt to optimize glycemic control. Acarbose, an alpha
      glucosidase inhibitor which delays carbohydrate digestion and the subsequent
      absorption of glucose, has been used with other agents to improve glycemic
      control. Also, in several clinical trials, acarbose monotherapy has been shown to
      result in significant reductions in postprandial plasma glucose levels as well as
      glycosylated hemoglobin. This agent is a useful addition to the current
      armamentarium for the treatment of NIDDM. Recently, the usefulness of acarbose as
      a first-line drug for the treatment of NIDDM has been evaluated and is reviewed
      here.

PMID- 8549019
TI  - Clinical experience with acarbose: results of a Canadian multicentre study.
AB  - Current therapeutic options for the treatment of non-insulin-dependent diabetes
      mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose
      concentrations. In several short-term studies, the alpha-glucosidase inhibitor,
      acarbose, has been reported to significantly lower post-prandial plasma glucose
      levels as well as HbA1c. The primary objective of this present study was to
      assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic
      control. Over a 1-y period, acarbose or placebo was administered to 4 groups of
      patients: those managed by diet only, diet and sulfonylurea, diet and biguanide,
      and diet and insulin. In all treatment groups, the addition of acarbose resulted
      in significant reductions in postprandial blood glucose levels. Additionally,
      HbA1C was significantly lower after 12 months of acarbose therapy, compared with
      placebo, in all groups except the diet and insulin group. The addition of
      acarbose consequently expands the armamentarium available to clinicians for the
      optimization of glycemic control in patients with NIDDM.

PMID- 8549020
TI  - The use of acarbose in the primary-care setting: evaluation of efficacy and
      tolerability of acarbose by postmarketing surveillance study.
AB  - The efficacy and tolerability of acarbose were examined in a postmarketing
      surveillance study of 10,462 patients (829 insulin-dependent diabetes mellitus
      (IDDM), 9,440 non-insulin-dependent diabetes mellitus (NIDDM), 193 not
      classified) during a 12-week treatment period. The median duration of diabetes
      was 60 months for men and 72 months for women in IDDM patients, and 40 months for
      men and 60 months for women in NIDDM patients. Of the Type II patients, 28.9%
      were treated with diet only; 58.1% additionally with sulfonylureas; 8.6% with
      insulin; and 4.3% with both sulfonylureas and insulin. The additional acarbose
      therapy led to a reduction of the mean fasting blood glucose levels (51 mg/dL for
      IDDM; 52 mg/dL for NIDDM) and 1 h postprandially (55 mg/dL for IDDM; 63 mg/dL for
      NIDDM). The HbA1 levels were reduced by 1.5%. Tolerability was good: 78.6% of
      patients had no adverse events; 19% reported meteorism/flatulence; 3.2%,
      diarrhea. Hypoglycemia was found in 0.8% of Type I and 0.6% of Type II patients
      who received concurrent insulin (n = 8) or glibenclamide (n = 1) treatment.
      Laboratory investigations gave no indication of other adverse effects, e.g.
      elevated levels of transaminases or creatinine. This postmarketing surveillance
      study documents the therapeutic benefit and the good tolerability of acarbose.

PMID- 8549021
TI  - Prevention of long-term complications of non-insulin-dependent diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) may be the most rapidly-growing
      chronic disease in the world. Its long-term complications, including retinopathy,
      nephropathy, neuropathy, and accelerated macrovascular disease cause major
      morbidity and mortality. Although therapy that normalizes glycemia may prevent
      the development and delay the progression of long-term complications in NIDDM, as
      has been demonstrated in insulin-dependent diabetes mellitus (IDDM), no direct
      data exist to support the efficacy of "intensive therapy" in NIDDM. An
      alternative approach to preventing the development of long-term complications may
      be to intervene more distally, i.e., inhibit the mechanism(s) by which elevated
      glucose levels cause complications. Potential pathogenic mechanisms include the
      accumulation of sorbitol and other biochemical changes in tissues with aldose
      reductase, and the modification of proteins by glycation. Pharmacologic probes,
      including aldose reductase inhibitors and glycation inhibitors such as
      aminoguanidine, are currently under study and may provide an efficient means of
      preventing complications, independent of the ambient glycemic level.

PMID- 8549022
TI  - Improving the action of insulin.
AB  - Improving the action of insulin is a relatively new concept in diabetes
      management. Insulin sensitivity can be improved by reduction of excessive body
      weight, regular physical activity and, possibly, by correcting a subclinical
      magnesium deficiency. Pharmacological means of improving insulin action include
      metformin, antiobesity serotoninergic agents and, possibly, benfluorex. New
      compounds aiming at improving the action of insulin are in development and
      include thiazolidinedione derivatives (known as "insulin sensitizers"),
      inhibitors of adipose tissue lipolysis (e.g. acipimox), and inhibitors of free
      fatty acid oxidation (e.g. etomoxir). Avoidance of drugs that reduce insulin
      sensitivity, such as beta blockers and thiazide diuretics, is recommended.
      Finally, cigarette smoking is associated with resistance to insulin but it
      remains to be demonstrated that cessation of cigarette smoking does in fact
      increase sensitivity to insulin.

PMID- 8549023
TI  - Pharmacokinetic-pharmacodynamic modelling as applied to bronchial asthma.

PMID- 8549024
TI  - The pharmacokinetic properties of topical levocabastine. A review.
AB  - The linear and predictable pharmacokinetic properties of the histamine H1
      receptor antagonist levocabastine make it particularly suitable for intranasal or
      ocular treatment of allergic rhinoconjunctivitis. Peak plasma concentrations
      (Cmax) occur within 1 to 2 hours of administration of single doses of
      levocabastine nasal spray and eye drops (0.2mg and 0.04mg, respectively). Drug
      absorption is incomplete after intranasal and ocular administration, with
      systemic availability ranging from 60 to 80% for levocabastine nasal spray and
      from 30 to 60% for the eye drops. However, as the amount of levocabastine applied
      intranasally and ocularly is small, the levocabastine plasma concentrations
      achieved are extremely low, with Cmax values in the ranges 1.4 to 2.2
      micrograms/L and 0.26 to 0.29 micrograms/L for intranasal and ocular
      administration, respectively. Pharmacokinetic-pharmacodynamic modelling has
      indicated that the clinical benefits of levocabastine are predominantly mediated
      through local antihistaminic effects, although some systemic activity may
      contribute to the therapeutic efficacy of levocabastine nasal spray during long
      term use. Levocabastine undergoes minimal hepatic metabolism, i.e. ester
      glucuronidation, and is predominantly cleared by the kidneys. Approximately 70%
      of parent drug is recovered unchanged in the urine. Plasma protein binding is
      approximately 55% and the potential for drug interactions involving binding site
      displacement is negligible. Furthermore, the pharmacokinetics of this agent do
      not appear to be influenced by either age or gender. Levocabastine nasal spray
      and eye drops may thus be considered suitable for the treatment of allergic
      rhinoconjunctivitis in a wide patient population.

PMID- 8549025
TI  - Pharmacokinetic-pharmacodynamic relationships for opioids in balanced
      anaesthesia.
AB  - The pure mu-receptor opioid agonists fentanyl, sufentanil and alfentanil are
      commonly used to provide the specific anti-nociceptive component of a balanced
      anaesthesia technique. Trefentanil and remifentanil are new opioids with a very
      short duration of action. Remifentanil has an ester structure and is very rapidly
      metabolised by blood and tissue esterases. Different perioperative stimuli
      require different plasma concentrations to suppress responses of the patient. The
      ability of the anaesthesiologist to select a precise dosage scheme for the
      individual patient is impeded by the large interindividual pharmacokinetic and
      pharmacodynamic variability. In addition, the combination of opioids and other
      drugs used to produce the desired components of balanced anaesthesia may exert
      additive, synergistic or antagonistic effects. Knowledge of factors influencing
      the pharmacokinetics and pharmacodynamics is still fragmentary and often
      controversial. Consequently, the opioid dose needs to be adjusted according to
      the responses of the patient during surgery to ensure adequate anaesthesia and
      rapid recovery. The duration of action is not predicted by the elimination half
      life alone. The decline in effect-site concentration is dependent on the complex
      entity of infusion duration, and pharmacokinetic and pharmacodynamic parameters.
      Computer simulations of infusions of varying duration have been extremely useful
      when selecting an opioid for a specific clinical scenario on a rational basis.
      Traditionally, opioids are still administered by intermittent bolus injections. A
      disadvantage of this method of administration is that plasma concentrations
      fluctuate above and below the level required for adequate anaesthesia. Computer
      assisted infusion pumps make it possible to target a particular drug
      concentration in plasma and to maintain or change this concentration as needed.
      This technique provides more stable anaesthesia and a more rapid recovery of the
      patient.

PMID- 8549026
TI  - Concentration-effect relationship of levodopa in patients with Parkinson's
      disease.
AB  - Studies on the concentration-effect relationship of levodopa in Parkinson's
      disease have established that: (1) in patients with a fluctuating response to
      levodopa, concentration-effect profiles are steeper and markedly shifted to the
      right (i.e. potency is decreased) compared with those patients whose symptoms are
      adequately controlled; (2) with controlled-release (CR) preparations, the
      concentration-effect relationship indicates a decreased potency compared with
      conventional immediate-release (IR) preparations; and (3) coadministration of a
      dopamine receptor agonist (even at a subclinical dose) enhances the potency of
      levodopa. These findings support some current hypotheses on the origin of, and
      the pathophysiological process underlying, response fluctuations. In patients
      with response fluctuations, metabolism of levodopa and storage of dopamine in the
      striatum are reduced. Levodopa is decarboxylated in the extracellular space, with
      the result that dopamine is released directly to the effect site. Thus, without
      dopamine storage acting as a buffer between levodopa metabolism and dopaminergic
      effect, the decline in motor response closely follows the decrease in levodopa
      concentrations. Even small fluctuations of levodopa concentrations around the
      EC50 value (the concentration threshold necessary to produce a motor response)
      might be followed by response fluctuations. Patients with Parkinson's disease who
      do not have response fluctuations exhibit a residual capacity of production and
      storage of endogenous dopamine; thus, lower amounts of 'exogenous' dopamine
      (formed by decarboxylation of levodopa) are required. The storage buffer is
      responsible for a time lag between decline in peripheral plasma concentrations of
      levodopa and dopamine-induced motor response. Low doses of a dopamine receptor
      agonist increase the basal tonus of the striatum, but do not reach the threshold
      concentration for triggering a motor response. Because of the dichotomic
      character of the motor response, patients do not switch from an 'off' (not
      responding) phase to an 'on' (responding) phase. However, lower amounts of
      exogenous dopamine released in the synaptic cleft will be necessary to induce
      response. To date, pharmacokinetic-pharmacodynamic modelling does not give a
      clear answer as to whether response fluctuations are additionally induced by
      receptor desensitisation or inhibition of the active transport of levodopa across
      the blood-brain barrier by the main metabolite of levodopa, 3-O-methyldopa.
      Nevertheless, there is some evidence that higher plasma concentrations of
      levodopa are required for similar motor effects when CR preparations are compared
      with IR preparations. Attempts have been made to establish therapeutic drug
      monitoring of levodopa in patients with response fluctuations. The
      interindividual variability of EC50 values in single studies is relatively low
      (10% to a maximum of 50%), which might allow specification of a 'population'
      threshold plasma concentration (i.e. a minimal effective plasma concentration
      required to obtain clinical effects). However, considering the short elimination
      half-life of levodopa, it seems doubtful whether such target drug concentrations
      can be maintained as steady-state. A marked prolongation of the dosage interval
      with CR preparations might be limited by the higher threshold concentrations of
      levodopa necessary to maintain clinical effects.

PMID- 8549028
TI  - Should hematopoietic growth factors routinely be given concurrently with
      cytotoxic chemotherapy?

PMID- 8549029
TI  - Atovaquone inhibits the glucuronidation and increases the plasma concentrations
      of zidovudine.
AB  - The pharmacokinetic interaction between atovaquone, a 1,4-hydroxynaphthoquinone,
      and zidovudine was examined in an open, randomized, three-phase crossover study
      in 14 patients infected with human immunodeficiency virus. Atovaquone (750 mg
      every 12 hours) and zidovudine (200 mg every 8 hours) were given orally alone and
      in combination. Atovaquone significantly increased the area under the zidovudine
      concentration-time curve (AUC) (1.82 +/- 0.62 micrograms.hr/ml versus 2.39 +/-
      0.68 micrograms.hr/ml; p < 0.05) and decreased the oral clearance of zidovudine
      (2029 +/- 666 ml/min versus 1512 +/- 464 ml/min; p < 0.05). In contrast,
      atovaquone tended to decrease the AUC of zidovudine-glucuronide (7.31 +/- 1.51
      micrograms.hr/ml versus 6.89 +/- 1.42 micrograms.hr/ml; p < 0.1) and
      significantly decreased the ratio of AUC zidovudine-glucuronide/AUC zidovudine
      (4.48 +/- 1.94 versus 3.12 +/- 1.1; p < 0.05). The maximum concentration of
      zidovudine-glucuronide was significantly lowered by atovaquone (5.7 +/- 1.5
      versus 4.57 +/- 0.97 micrograms/ml; p < 0.05). Zidovudine had no effect on the
      pharmacokinetic disposition of atovaquone. Atovaquone appears to increase the AUC
      of zidovudine by inhibiting the glucuronidation of zidovudine.

PMID- 8549027
TI  - Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part I:
      Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide.
AB  - This article reviews 119 papers published since 1964 on the pharmacokinetics of
      phenobarbital, primidone, valproic acid, ethosuximide and mesuximide
      (methsuximide) in paediatric patients. Particular attention has been paid to the
      role of age in determining the variability of pharmacokinetic parameters, but the
      effect of other factors, such as different formulations and routes of
      administration, concomitant treatments, gender and pathological conditions other
      than epilepsy, have also been considered. Mean phenobarbital terminal half-life
      (t1/2z) is very long in neonates (45 to 409 hours) and decreases with age.
      Therefore, a low dose per kilogram (dose/kg) is recommended during the neonatal
      period. The dose requirement decreases with increasing age, especially in
      children also taking valproic acid, which inhibits phenobarbital metabolism.
      Primidone is metabolised to phenobarbital and phenylethylmalonilamide; the
      metabolic conversion rate is increased by enzyme-inducing drugs and inversely
      correlated with age, being virtually absent in neonates. Valproic acid is
      extensively bound to plasma proteins, but there is a high interindividual and
      intraindividual diurnal variability in the binding, which depends on the
      concentration of binding proteins (i.e. albumin) and binding modulators (e.g.
      free fatty acids) but not on age (at least in those patients aged between 3
      months and 65 years). The clearance (CL/F) of valproic acid positively correlates
      with the unbound concentrations and is strongly age-dependent, being low in
      neonates and high at the end of the first postnatal month, and progressively
      decreasing from 2 months to 14 years. The combination of these factors leads to a
      very poor correlation between plasma concentrations and dose/kg (C/D) and between
      plasma concentrations of total valproic acid and efficacy. Children also taking
      enzyme-inducing antiepileptic drugs require a larger valproic acid dose/kg,
      whereas the coadministration of aspirin (acetylsalicylic acid) may decrease the
      clearance of unbound drug (CLu/F), and thus require a decrease in the daily dose
      of valproic acid. Ethosuximide is well absorbed, minimally protein bound and
      slowly eliminated. Lower C/D ratios are reported in children younger than 10
      years old than in older children and in individuals also taking enzyme-inducing
      drugs (i.e. primidone). According to the only available paper on mesuximide in
      paediatric patients, the C/D ratio is less sensitive to both age and associated
      therapy.

PMID- 8549030
TI  - Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite
      of the anti-varicella zoster virus agent netivudine.
AB  - OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on
      dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them
      to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS:
      Three groups of eight elderly volunteers received 400 or 800 mg netivudine or
      placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil,
      an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed
      before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of
      netivudine and 5-propynyluracil were determined after the last dose. RESULTS:
      Plasma uracil was unquantifiable in all subjects before the first dose and at all
      time points in the placebo group. In recipients of netivudine it reached a
      plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8
      in the subjects who received 400 and 800 mg. Plasma netivudine concentrations
      were approximately dose proportional, but 5-propynyluracil concentrations were
      similar in both groups. The half-maximal rise in plasma uracil occurred after a
      cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be
      achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine
      dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase.
      Coadministration with the antimetabolite 5-fluorouracil will require a
      substantial reduction in 5-fluorouracil dose to avoid toxicity but may also
      improve the therapeutic index of 5-fluorouracil.

PMID- 8549031
TI  - Pharmacokinetics of vinorelbine in patients with liver metastases.
AB  - BACKGROUND: The main elimination pathway of vinorelbine is hepatic metabolism,
      and the clearance of vinorelbine could be reduced in patients with liver
      metastases. OBJECTIVES: To study the pharmacokinetics of vinorelbine in patients
      who have advanced breast cancer with or without liver metastases and to study the
      relationship between hepatic function and vinorelbine clearance. PATIENTS AND
      METHODS: We studied 29 patients with advanced breast cancer: 19 with liver
      metastases and 10 control patients with extrahepatic metastases (mean age, 61
      years; age range, 38 to 81 years). The vinorelbine dose was 30 mg/m2 as a short
      intravenous infusion; the dose was reduced by 50% in patients with bilirubin > 2
      mg/dl. Patients were classified by ultrasonographic estimation of the liver
      volume replaced by tumor (%LVRT). Standard liver function tests and a
      monoethylglycinexylidide test (a quantitative liver function test based on
      lidocaine metabolite formation) were performed. Vinorelbine was assayed in plasma
      by HPLC with fluorescence detection. Vinorelbine determination was impossible in
      two patients with more than 75% LVRT because of interferences. Pharmacokinetic
      parameters were calculated with a noncompartimental method and compared by means
      of the Kruskal-Wallis test. RESULTS: A lower vinorelbine clearance rate was
      observed in the five patients with more than 75% LVRT (22.9 L/hr/m2) compared
      with the 10 patients with no liver metastases (48.0 L/hr/m2) and the 12 patients
      with 25% to 75% LVRT (45.3 L/hr/m2). Terminal elimination half-life and apparent
      volume of distribution were not significantly different among groups. The
      monoethylglycinexylidide test had a significant correlation with vinorelbine
      clearance. (r2 = 0.70; p = 10(-4). CONCLUSIONS: These results support vinorelbine
      dose reduction in patients with severe liver failure but not in patients with
      moderate secondary liver involvement. The monoethylglycinexylidide test may prove
      to be useful for vinorelbine dose individualization.

PMID- 8549032
TI  - Decreased intestinal CYP3A in celiac disease: reversal after successful gluten
      free diet: a potential source of interindividual variability in first-pass drug
      metabolism.
AB  - BACKGROUND: Cytochrome P450 (CYP) 3A is constitutively expressed in human
      intestinal villi and may account for significant "first-pass" prehepatic
      metabolism of a number of drugs in the intestine. Celiac disease results in small
      intestinal atrophy. We hypothesized that this would result in a loss of CYP3A.
      METHODS: Formalin-fixed jejunal biopsy specimens taken from nine patients with
      celiac disease at variable times before and after treatment with a gluten-free
      diet were immunoperoxidase stained after incubation with anti-CYP3A4 rabbit
      antisera (1:2000 dilution). The amount of immunoreactive CYP3A was determined by
      two observers who were blinded to the treatment states of the patients. Staining
      intensity was graded on a numerical scale from 1 to 4+ on the basis of intensity
      of staining in individual enterocytes, as well as the total number of enterocytes
      stained. RESULTS: Slides of biopsy specimens from all nine untreated patients
      with celiac disease were graded 1. Treatment with a gluten-free diet was
      associated with a significant increase in CYP3A immunoreactive protein in small
      bowel biopsy specimens (p < 0.05, Wilcoxon signed-rank test). CONCLUSIONS: We
      conclude that patients with celiac disease have low intestinal CYP3A
      immunoreactivity and that treatment with a gluten-free diet is associated with an
      increase in intestinal CYP3A immunoreactive protein. Our findings suggest that
      intestinal disease and variability in intestinal CYP3A activity might be an
      unexamined variable that may contribute to interindividual variability in drug
      disposition.

PMID- 8549033
TI  - Comparison of the dapsone recovery ratio and the erythromycin breath test as in
      vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving
      cyclosporine.
AB  - INTRODUCTION: Cytochrome P4503A (CYP3A) is primarily responsible for the
      metabolism of cyclosporine and that of many other drugs. Several substrates of
      CYP3A have been investigated for use as pharmacologic probes to predict the CYP3A
      metabolizing capacity of an individual and, therefore, the disposition of other
      CYP3A substrate drugs. One such measure of CYP3A activity is the 14C erythromycin
      breath test, which has been applied to the prediction of cyclosporine
      disposition. However, the test has practical limitations. Because of this, the 0-
      to 8-hour urinary dapsone recovery ratio has been studied as an alternative and
      more practical probe of CYP3A activity. METHODS: The dapsone recovery ratio and
      the 14C erythromycin breath test were correlated with cyclosporine concentrations
      in 16 patients with rheumatoid arthritis to determine the usefulness of the
      dapsone recovery ratio as an alternative to the 14C erythromycin breath test. The
      erythromycin breath test showed a fourfold variation between subjects and
      correlated weakly with trough cyclosporine concentrations (r = -0.50, p < 0.05),
      whereas the dapsone recovery ratio varied only approximately twofold between
      subjects and did not correlate with trough cyclosporine concentrations (r = 0.02,
      p = 0.94). The correlation between the dapsone recovery ratio and the
      erythromycin breath test (r = 0.22, p = 0.41) was not significant. CONCLUSIONS:
      These data suggest that results obtained with one probe in vivo may not apply to
      another CYP3A substrate. The poor quantitative relationship between cyclosporine
      concentrations and the erythromycin breath test limits its usefulness in the
      prediction of an individual's cyclosporine dose requirement.

PMID- 8549034
TI  - Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone.
AB  - Plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined
      after administration of 20 mg oral controlled-release oxycodone tablets to four
      subject groups: young (aged 21 to 45 years) men, elderly (aged 65 to 79 years)
      men, young women, and elderly women. Area under the oxycodone and noroxycodone
      concentration-time curve (AUC) values were comparable among the four groups.
      Compared with oxycodone, the oxymorphone AUC values were small, with significant
      differences between subject groups. AUC values were also calculated for the
      pharmacodynamic variable "drug effect," scored on a 100 mm visual analog scale.
      The two groups with the highest oxycodone AUC values (young and elderly women)
      had the lowest oxymorphone AUC values and the greatest drug effect AUC values.
      The two groups with the lowest oxycodone AUC values (young and elderly men) had
      the highest oxymorphone AUC values and the lowest drug effect AUC values. These
      results support oxycodone, and not oxymorphone, as being primarily responsible
      for pharmacodynamic and analgesic effects.

PMID- 8549035
TI  - Grapefruit juice and its flavonoids inhibit 11 beta-hydroxysteroid dehydrogenase.
AB  - INTRODUCTION: The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD)
      oxidizes cortisol to inactive cortisone. Its congenital absence or inhibition by
      licorice increases cortisol levels at the mineralocorticoid receptor, causing
      mineralocorticoid effects. We tested the hypothesis that flavonoids found in
      grapefruit juice inhibit this enzyme in vitro and that grapefruit juice itself
      inhibits it in vivo. METHODS: Microsomes from guinea pig kidney cortex were
      incubated with cortisol and nicotinamide adenine dinucleotide (NAD) or
      nicotinamide adenine dinucleotide phosphate (NADP) and different flavonoids and
      the oxidation to cortisone measured with use of HPLC analysis. In addition,
      healthy human volunteers drank grapefruit juice, and the ratio of cortisone to
      cortisol in their urine was measured by HPLC and used as an index of endogenous
      enzyme activity. RESULTS: Both forms of 11 beta-OHSD requiring either NAD or NADP
      were inhibited in a concentration-dependent manner by the flavonoids in
      grapefruit juice. Normal men who drank grapefruit juice had a fall in their
      urinary cortisone/cortisol ratio, suggesting in vivo inhibition of the enzyme.
      CONCLUSION: Dietary flavonoids can inhibit this enzyme and, at high doses, may
      cause an apparent mineralocorticoid effect.

PMID- 8549036
TI  - Rifampin drastically reduces plasma concentrations and effects of oral midazolam.
AB  - BACKGROUND: Midazolam is a short-acting benzodiazepine that is metabolized by
      CYP3A enzymes. Rifampin is a potent enzyme inducer that may seriously interact
      with some substrates of CYP3A4. METHODS: The possible interaction between
      rifampin and midazolam was investigated in a double-blind, randomized crossover
      study of two phases. Rifampin (600 mg once daily) or placebo was administered to
      10 healthy subjects for 5 days. On the sixth day, the subjects were given 15 mg
      oral midazolam. Plasma samples were collected for determination of midazolam, and
      pharmacodynamic effects were measured for 10 hours. RESULTS: Rifampin
      pretreatment decreased the area under the plasma midazolam concentration-time
      curve by 96% (i.e., from 10.2 +/- 0.8 to 0.42 +/- 0.05 micrograms.min/ml [mean +/
      SEM; p < 0.001]) and the maximum concentration by 94% (i.e., from 55 +/- 4 to
      3.5 +/- 0.7 ng/ml [p < 0.001]). The elimination half-life of midazolam was
      decreased from 3.1 +/- 0.2 to 1.3 +/- 0.2 hours by rifampin (p < 0.001). During
      the rifampin phase, the pharmacodynamic effects of midazolam were markedly
      smaller than the effects during the placebo phase in all the tests (e.g., the
      Digit Symbol Substitution Test; p < 0.001). CONCLUSIONS: The observed substantial
      decrease in plasma concentrations and effects of midazolam most likely results
      from induction of CYP3A4 by rifampin in both the gut wall and the liver. Orally
      administered midazolam is ineffective during rifampin treatment.

PMID- 8549037
TI  - Differential effects of oral losartan and enalapril on local venous and systemic
      pressor responses to angiotensin I and II in healthy men.
AB  - This double-blind, placebo-controlled crossover study was designed to
      differentiate the pharmacodynamic effects of the angiotensin II receptor
      antagonist losartan from the angiotensin converting enzyme inhibitor enalapril.
      Effects of placebo, enalapril (10 mg), and losartan (20 and 100 mg) on local
      venous and systemic pressor responses to angiotensin I and II were compared in
      eight healthy male subjects. Treatments were administered orally approximately 4
      hours before agonist infusions into a dorsal hand vein. Local changes in hand
      vein diameter and systemic blood pressure were monitored during the infusions.
      The 100 mg dose of losartan attenuated local venoconstrictor and systemic pressor
      responses to angiotensin I and II. In contrast, enalapril blocked only responses
      to angiotensin I. Both losartan and enalapril increased plasma renin
      concentration compared with placebo. These results are consistent with direct
      antagonism of angiotensin II receptors by losartan and with indirect effects of
      enalapril through inhibition of angiotensin converting enzyme.

PMID- 8549038
TI  - The impact of sedative-hypnotic use on sleep symptoms in elderly nursing home
      residents.
AB  - OBJECTIVE: To determine the frequency of sleep-related complaints among
      institutionalized elderly subjects and to assess the relationship between
      perceived sleep quality and the use of sedative-hypnotic agents and other
      psychoactive medications. METHODS: In 12 nursing homes in Massachusetts, we
      conducted observational, cross-sectional, and longitudinal studies of 145
      institutionalized elderly subjects (average age, 83.0 years; age range, 65 to 105
      years). We recorded the patients' demographic characteristics and all medication
      use (both scheduled and as needed) during a 1-month baseline period. A research
      assistant who was blinded to diagnoses and medication use performed detailed
      neuropsychologic testing and administered a series of standardized questions
      concerning difficulty sleeping, early morning awakening, and time spent awake in
      bed. Medication use and patient assessments were repeated after a 6-month
      interval. RESULTS: One or more sleep-related complaints were present at baseline
      in 94 (65%) of the residents studied. Using logistic regression to adjust for
      potential confounding, we found no relationship in the baseline month between use
      of sedative-hypnotic agents and the presence or absence of sleep complaints.
      After 6 months of follow-up, 27 (19%) of the residents had decreased their use of
      sedative-hypnotic agents and 23 (16%) had increased their use. However, there was
      no relationship between decreased use of sedative-hypnotic agents and worsened
      sleep (p > 0.20) or between their increased use and improved sleep reports (p >
      0.10). Improvement in functional status was significantly associated with
      improved sleep at follow-up (p < 0.005). CONCLUSIONS: Sleep complaints occur in
      the majority of institutionalized elderly persons. Neither cross-sectional nor
      longitudinal analyses showed a relationship between patterns of sedative-hypnotic
      use and the presence, absence, or change in sleep complaints.

PMID- 8549040
TI  - Pictorial review: MR imaging of neuronal migration anomalies.
AB  - Neuronal migration anomalies form a spectrum of congenital brain malformations
      with a variety of clinical manifestations. The widespread use of MRI in the
      investigation of neurological symptoms, and particularly in the imaging of
      epilepsy, has made the correct recognition and interpretation of these disorders
      important. This pictorial summary describes the typical clinical features and the
      MR appearances of this group of conditions. For a more detailed review which
      includes pathological correlation, the reader should refer to an excellent
      article by Barkovitch and colleagues (Barkovitch A.J., Gressens P, Evrard P.
      Formation, maturation and disorders of brain neocortex.

PMID- 8549039
TI  - Temporomandibular joint imaging.

PMID- 8549042
TI  - MRI characteristics of chondroblastoma.
AB  - We report a retrospective study of MR imaging of 16 patients with histologically
      proven chondroblastoma, 12 at primary presentation and four clinically suspected
      recurrences. In all the primary cases MR imaging showed a lobulated low signal
      intensity (SI) rim. Low SI foci within the tumour were present in 11 out of the
      12 cases and corresponded to calcification seen on radiographs or CT. Bone marrow
      oedema was also present in 11 out of 12 cases and an adjacent joint effusion in
      eight out of 12. The STIR sequence was of particular value, giving optimal
      delineation of marrow and soft tissue oedema. Of the suspected recurrences one
      showed peritumoral oedema and was subsequently proven histologically. Three
      showed no peritumoral oedema and subsequent histology was negative in these
      cases. The presence or absence of oedema may be a useful indicator of tumour
      activity although further study is required.

PMID- 8549041
TI  - Three-dimensional time-of-flight MR angiography of the arch of aorta and its
      major branches: a comparative study with contrast angiography.
AB  - The region of the arch of aorta and the intrathoracic course of its major
      branches was evaluated in 11 patients using three-dimensional time-of-flight
      magnetic resonance (MR) angiography. Abnormalities such as stenosis, occlusion,
      dilatation and aneurysm formation were documented in the innominate, both common
      carotid and both subclavian arteries. The results were compared with those of
      contrast angiography. There was a good correlation in 47 of the 55 arteries
      compared. There were five false positive results including overestimation of a
      stenosis, and three false negative results including underestimation of a
      stenosis. MR angiography had a sensitivity of 93% and a specificity of 89% for
      correctly detecting or excluding an abnormality. These results suggest that three
      dimensional time-of-flight MR angiography demonstrates lesions in the major
      branches of the arch of aorta fairly accurately and will prove useful in the
      initial evaluation and in follow up studies.

PMID- 8549043
TI  - The unreliability of CT scans and initial chest radiographs in evaluating blunt
      trauma induced diaphragmatic rupture.
AB  - OBJECTIVE: There is no gold standard for early and reliable diagnosis of
      traumatic diaphragmatic rupture (TDR). The purpose of this study is to correlate
      CT scans, chest radiographs, and intubation on the ability to diagnosis traumatic
      diaphragmatic rupture. MATERIALS AND METHODS: Twenty patients with blunt trauma
      induced diaphragmatic rupture were identified from a five year review of a Level
      1 Trauma Registry. RESULTS: Ten of the 20 (50%) patients had TDR on initial chest
      X-ray, all on the left side. Twelve patients had both chest X-rays and a chest
      and abdominal CT scan; however, only five (42%) of the CT scans were diagnostic.
      Of the 12 patients initially intubated, TDR was diagnosed in only four (33%)
      patients on initial chest X-ray and in one (14%) of seven patients having chest
      and abdominal CT scans and being intubated. CONCLUSION: The early diagnosis of
      blunt traumatic diaphragmatic rupture, especially in intubated patients,
      continues to be a diagnostic dilemma. There is a significantly better possibility
      of identifying left over right-sided TDR (P < or = 0.05). Diagnosing TDR is also
      facilitated by extubation. If the suspicion exists, a post extubation chest
      radiograph should be performed to evaluate for TDR.

PMID- 8549044
TI  - CT demonstration of intracranial bleeding in term newborns with mild clinical
      symptoms.
AB  - This paper presents symptomatic term newborns with negative ultrasound
      examination which showed intracranial bleeding demonstrated by CT scan. Fifty
      eight term newborns with Apgars of 9-10 were referred for repeat CT examination
      of the brain with symptoms, such as apnea, disturbances of swallowing or sucking,
      impaired muscular tonus, tremor and jerks. The ultrasound examination in all was
      normal. The first CT scan was performed 12-13 h after delivery. The second CT
      scan was performed at least two weeks later. Twenty-three of the patients
      underwent lumbar puncture. Physical examination was performed on each patient--at
      birth and one week later. The clinical symptoms were still present at the time of
      the second physical examination. Fourteen to seventeen months following the
      delivery, the psychomotor development was evaluated in 29 of the children using
      the Gesell test. In five children, the diagnosis of psychomotor retardation was
      established which correlated with the brain atrophy demonstrated on CT. Twenty
      three newborns who underwent lumbar puncture showed evidence of bleeding into the
      subarachnoid space. The blood haemoglobin levels of all the cases was below 18
      g/dl. The first CT examination demonstrated blood in the subarachnoid space. The
      second CT scan did not demonstrate any findings. Intracranial bleeding in
      newborns may be associated with normal delivery. The demonstration of high
      densities in the first CT scan, the normal second CT scan, the blood tinged or
      xantochromic CSF and the normal blood haemoglobin levels are indicative of
      intracranial bleeding.

PMID- 8549045
TI  - Is ipsilateral mammography worthwhile in Paget's disease of the breast?
AB  - AIMS: To identify the clinical value of pre-operative ipsilateral mammography in
      patients with Paget's disease of the breast. METHOD: The mammograms and
      histological data of 27 patients with Paget's disease and 60 patients with
      symptomatic DCIS without Paget's disease were reviewed and compared. RESULTS:
      Forty-four percent of patients with Paget's disease had normal mammograms.
      Mammography did not discriminate between DCIS and invasive disease, and could not
      predict DCIS sub-type. DCIS was large cell in 80% of patients with Paget's
      disease. Given that large cell DCIS in non Paget's patients is normally visible
      mammographically, the large proportion of Paget's patients with normal
      mammography is difficult to explain, but could be due to the small size of the
      lesions. Comparison of the Paget's and non-Paget's groups showed that large cell
      solid disease was more common, small cell cribriform less common and normal
      mammography more common in the Paget's group. Given that mastectomy is the
      treatment of choice, the only clinical value of ipsilateral mammography in our
      unit would be to allow image guided core biopsy of any detected mammographic
      abnormalities to determine the presence of invasive disease prior to surgery,
      thus indicating the need for node sampling pre-operatively rather than as a
      delayed procedure. This study also confirms that mammography is of little help in
      deciding if breast conserving surgery is appropriate for individual cases of
      Paget's disease of the nipple due to the insensitivity of mammography in showing
      the site of disease.

PMID- 8549046
TI  - Antibiotic prophylaxis in patients undergoing radiological procedures who are at
      risk of infective endocarditis--do radiologists know what they are doing?
AB  - The British Society for Antimicrobial Chemotherapy has published guidelines
      recommending that all patients with prosthetic heart valves, or those with a
      previous history of bacterial endocarditis, should receive prophylactic
      antibiotics before procedures likely to cause a bacteraemia, due to the potential
      risk of bacterial endocarditis. The guidelines are widely available, notably in
      the British National Formulary. Two separate and independent surveys of
      radiologists in this Region showed that there was poor awareness of these
      guidelines and their implications for radiology departments.

PMID- 8549047
TI  - Palliation of malignant tracheo-oesophageal fistula using covered metal stents.
AB  - Nine patients presenting with malignant tracheo-oesophageal fistula have been
      treated by placing covered oesophageal stents (seven Wallstent, two Gianturco)
      within the oesophageal lumen over a twelve month period. Five patients had
      oesophageal carcinoma, two bronchial carcinoma, one metastatic renal cell
      carcinoma, one developed malignant change within a longstanding tuberculous
      tracheo-oesophageal fistula. Initial closure of the fistula was successful in six
      cases. Three failed due to technical problems (one with a Wallstent and both
      cases with the Gianturco stents). There were no immediate complications and
      normal diet resumed within 24 h in the six successful cases. One patient was
      aware of the physical presence of the stent (for a high fistula), the remainder
      of the stents were well tolerated. Covered metal stents offer a minimally
      invasive, effective form of palliation in certain patients with malignant tracheo
      oesophageal fistulae. Accurate positioning using fluoroscopic guidance is
      essential in gaining optimal stent position.

PMID- 8549048
TI  - A review of the statistical analysis used in papers published in Clinical
      Radiology and British Journal of Radiology.
AB  - Statistical analysis such as significance testing have become essential features
      of published medical studies. This has resulted in an increased frequency with
      which statistics are used, making the interpretation of scientific publications
      more difficult. There is an extensive array of tests and techniques. The aim of
      this study is to identify which statistical tests are used in radiology
      publications. All major articles published in Clinical Radiology and British
      Journal of Radiology in one year were reviewed. The frequency of statistical
      methods used was as follows: no statistical method or descriptive statistics only
      103 (47%), one type of statistical method 67 (31%), and two or more methods 47
      (22%). Statistics dealing with basic inference, decisions, contingency tables or
      correlation/regression techniques were found in 124 (53%) in which a procedure
      had been used. Advanced statistics including receiver operating characteristics
      (ROC), odds ratio, regression techniques, multiway ANOVA, and nonparametric ANOVA
      studies accounted for only 41 (19%) in which a procedure had been used. We
      conclude that descriptive analysis and basic statistical techniques account for
      most of the statistical tests reported. Physicians should concentrate on
      improving their understanding of basic statistics but advice should be sought
      from professionals in the fields of biostatistics and epidemiology as to whether
      the use of more advanced techniques would be more appropriate.

PMID- 8549049
TI  - The imaging diagnosis of hepatic schistosomiasis japonicum sequelae.
AB  - We reviewed the ultrasound (US) and computed tomography (CT) examinations of the
      liver in 21 patients with hepatic schistosomiasis japonicum (HSJ), to assess the
      role of imaging in its diagnosis. Thirteen patients had histopathological
      evidence of hepatic ova deposition. A 'network' pattern was present in 14 of 17
      (82%) patients on US, and 'turtle-back' calcification in 11 of 13 (85%) patients
      on non-contrast CT (NCCT). The combination of US and NCCT was positive for HSJ in
      all nine patients subjected to both investigations. These findings are specific
      for HSJ and we discuss how they differ from the imaging findings reported in
      hepatic Schistosoma mansoni (HSM). We conclude that the sequelae of HSJ infection
      create an imaging diagnosis. Although an uncommon incidental finding at liver
      imaging, the combined US and CT appearances are so characteristic that in the
      majority of patients biopsy can potentially be avoided.

PMID- 8549050
TI  - Technical report: spiral CT pneumocolon for suspected colonic neoplasms.
AB  - Abdominal spiral computed tomography (CT) pneumocolon is performed after
      cleansing the colon, using a smooth muscle relaxant and rectal air insufflation.
      Rapid dynamic scanning is undertaken with intravenous contrast to give optimal
      hepatic and vascular enhancement, and 5-10 mm contiguous slices. The area of
      interest in the colon is reconstructed every 2.5 mm. This technique was performed
      in four patients with colorectal cancer and the CT findings were compared with
      the barium enema and pathology following surgical resection. Spiral CT
      pneumocolon clearly showed the primary tumour in all cases as an enhancing soft
      tissue mass, and was able to detect local extension and lymphadenopathy as well
      as assess the liver, peritoneum and remaining abdomen. CT depicted the morphology
      of the primary tumour more clearly than barium enema, and in one case also
      detected a 1 cm polyp which was not seen on the barium study because the patient
      was incontinent of barium and views were limited. There was good correlation
      between the CT and pathological findings. Compared to a barium enema, spiral CT
      pneumocolon is quick, with minimal patient discomfort, no risk of barium
      incontinence, and there is good assessment of the local and distant abdominal
      disease. Multiplanar formatting is possible and 3-D reconstruction gives intra-
      and extra-luminal views.

PMID- 8549051
TI  - Case report: true massive thymic hyperplasia.

PMID- 8549052
TI  - Case report: primary malignant rhabdoid tumour of the brain.

PMID- 8549053
TI  - Case report: elastofibroma dorsi: a pseudomalignant lesion.

PMID- 8549054
TI  - Case report: renal granuloma following intra-vesical bacillus Calmette-Guerin.

PMID- 8549055
TI  - Case report: transient unilateral cerebral oedema in hemiplegic migraine: MR
      imaging and angiography.

PMID- 8549056
TI  - Pre-operative cervical spine radiography in rheumatoid arthritis.

PMID- 8549057
TI  - Appropriateness of use and the clinical impact of MCU in clinical practice.

PMID- 8549058
TI  - Dynamic contrast enhanced MR.

PMID- 8549059
TI  - Abnormal left ventricular diastolic function during cold pressor test in
      uncomplicated insulin-dependent diabetes mellitus.
AB  - 1. Insulin-dependent diabetes mellitus is a known risk factor for congestive
      heart failure and an early diastolic dysfunction has been described. In order to
      see if diabetes itself and not complications like hypertension, nephropathy or
      ischaemic heart disease can be considered responsible for the abnormal diastolic
      function of the left ventricle, 17 young patients with uncomplicated insulin
      dependent diabetes mellitus and 12 control subjects were exposed to a cold
      pressor test. 2. Blinded echo-Doppler examination was performed before and during
      the test. During basal conditions, left ventricular dimensions and volumes were
      smaller in diabetes and atrial contributions to left ventricular filling were
      increased. 3. During the cold pressor test, isovolumic relaxation time increased,
      peak early filling velocity (E) decreased, E deceleration time decreased and
      atrial contribution (A) increased significantly in diabetes, while only A
      increased in the control group. A marked increase in left atrial ejection force
      was seen in diabetes only (P < 0.002). This difference was seen in spite of
      comparable reductions in mitral area and atrioventricular compliance in the two
      groups. 4. The hyperfunction of the left atrium in diabetes is hypothesized to be
      due to reduce size of the left ventricle combined with incipient autonomic
      neuropathy.

PMID- 8549060
TI  - Microvascular response to tissue injury and capillary ultrastructure in the foot
      skin of type I diabetic patients.
AB  - 1. Microvascular blood flow responses to injury and capillary ultrastructure were
      assessed by laser Doppler flowmetry and detailed light and electron microscopy
      respectively in skin biopsied from 28 patients with insulin-dependent diabetes
      and 17 control subjects. 2. The hyperaemic response induced by biopsy (P < 0.001)
      and heating to 44 degrees C (P < 0.001) was significantly lower in the diabetic
      patients and showed progressive impairment with the severity of complications (P
      < 0.001). 3. Skin capillary basement membrane thickness was significantly
      increased in the diabetic patients (P < 0.001) and also increased with the
      severity of complications (P < 0.002). Both the luminal area (P < 0.001) and the
      endothelial cell outer perimeter (P < 0.002), measures of luminal and capillary
      size, respectively, were significantly reduced in all diabetic patients. 4.
      Basement membrane thickness was related significantly to the impaired hyperaemic
      response to both biopsy (P < 0.01) and thermal injury (P < 0.01). 5. Our findings
      support the hypothesis that structural abnormalities, which are characterized by
      an early reduction in capillary size and later thickening of basement membrane,
      form an important mechanism for the impaired hyperaemic response in diabetic
      patients.

PMID- 8549061
TI  - Effect of acute and chronic caffeine use on the cerebrovascular, cardiovascular
      and hormonal responses to orthostasis in healthy volunteers.
AB  - 1. The effects of acute and chronic caffeine ingestion on supine- and tilt- (60
      min at 70 degrees) induced changes in middle cerebral artery velocity (Vmca),
      heart rate, blood pressure and counter-regulatory hormone levels (catecholamines,
      growth hormone and cortisol) were studied in nine healthy volunteers. A double
      blind, placebo-controlled design was used to study acute effects followed by an
      open study after 6 days of chronic caffeine use. 2. In the supine position, acute
      ingestion of caffeine (250 mg) was associated with a fall in Vmca [-11 cm/s,
      point estimate of difference versus placebo (95% confidence interval: -17, -6)
      cm/s, P < 0.001] and a rise in mean arterial pressure [+4 (1, 6) mmHg, P < 0.01]
      and plasma adrenaline levels [+138 (53, 223) pmol/l, P < 0.01]. After chronic
      caffeine use, the pressor and adrenaline responses, but not the drop in Vmca,
      were significantly attenuated. 3. On tilting to 70 degrees the fall in Vmca was
      greater with placebo than after acute caffeine ingestion [-10 (-14, -15) cm/s, P
      < 0.01], whereas increments (above supine values) in heart rate, mean arterial
      pressure and hormone levels were unchanged by caffeine. In contrast, the
      adrenaline [+126 (29, 282) pmol/l, P < 0.01] and noradrenaline [+0.6, 0.9)
      nmol/l, P < 0.05] responses to tilting were augmented after acute caffeine
      ingestion. Chronic caffeine supplementation did not alter the fall in Vmca
      associated with tilting, but significantly attenuated the adrenaline response (P
      < 0.01 compared with the acute study). 4. Acute caffeine ingestion and
      orthostasis are both associated with a reduction in Vmca and a rise in mean
      arterial pressure and adrenaline levels. The acute effects of caffeine on mean
      arterial pressure and adrenaline but not on Vmca are lost with sustained caffeine
      intake. These results suggest dissociation between the development of central and
      peripheral tolerance after chronic caffeine use.

PMID- 8549062
TI  - Potent inhibitory effect of SR 49059, an orally active non-peptide vasopressin
      VIa receptor antagonist, on human arterial coronary bypass graft.
AB  - 1. The effect of vasopressin receptor antagonists varies between analogues
      (peptide, non-peptide) and across species. In this study the effect of the novel
      non-peptide vasopressin V1a receptor antagonist SR 49059 on human internal
      mammary arteries was investigated. 2. SR 49059 produced a potent, concentration
      dependent, inhibitory effect on vasopressin-induced contraction of human coronary
      bypass graft internal mammary arteries. Both SR 49059 (1 mumol/l) and a peptide
      selective V1a antagonist ([d(CH2)5sarcosine7]arginine vasopressin) (1 mumol/l)
      abolished vasopressin-induced contraction. The non-peptide V1a receptor
      antagonist OPC-21268 (1 mumol/l) had no effect on vasopressin-induced
      contraction. 3. The effect of SR 49059 was specific to vascular vasopressin
      receptors as noradrenaline-induced contraction was not influenced by SR 49059. 4.
      The results of this study in vitro indicate that the non-peptide SR 49059 is a
      potent, specific vasopressin V1a receptor antagonist in the human internal
      mammary artery and suggest that it may be a useful tool for studying the
      pathophysiological role of vasopressin in man.

PMID- 8549063
TI  - Differences in transcription and translation of long and short Gs alpha, the
      stimulatory G-protein, in human atrium.
AB  - 1. We have previously reported the relative mRNA and protein level of the long
      and short splice variants of Gs alpha (Gs alpha L and Gs alpha S) in human
      atrium. We have now measured the relative proportions of the serine+ and serine-
      variants of Gs alpha L and Gs alpha S in human atrium, and assessed, indirectly,
      whether their differential expression may (i) regulate Gs alpha phosphorylation,
      and (ii) be regulated by atrial cyclic AMP levels. 2. The serine+ and serine-
      variants of Gs alpha L and Gs alpha S were estimated by single nucleotide primer
      extension in 36 right atrial strips of which half were from beta-adrenoceptor
      blocked patients. The ratio of serine+ to serine- variants was 0.06 +/- 0.12 for
      Gs alpha L, compared with 8.04 +/- 12.16 for Gs alpha S (P < 0.001). 3.
      Isoelectric points of Gs alpha and Gs alpha S in the atria of four beta
      adrenoceptor-blocked and four non-beta-adrenoceptor-blocked patients were
      estimated by two-dimensional gel electrophoresis. Two-dimensional gel analysis
      gave a consistent pattern with several spots for both Gs alpha L and Gs alpha S;
      however, the isoelectric points of Gs alpha S were more acid (5.18 +/- 0.24) than
      those of Gs alpha L (5.87 +/- 0.17, P < 0.001). 4. No significant difference in
      either the serine variants or isoelectric point value was observed between beta
      adrenoceptor-blocked and non-beta-adrenoceptor-blocked patients. 5. In
      conclusion, all four Gs alpha variants were expressed in human atrium, but Gs
      alpha L is almost entirely of the serine- form. Gs alpha S has a more acidic
      isoelectric point than Gs alpha L, indicating a possible post-translational
      modification. The lack of difference in our results between beta-adrenoceptor
      blocked and non-beta-adrenoceptor-blocked patients suggests indirectly that
      cyclic AMP is an unlikely candidate for regulating splicing or post-translational
      modification of Gs alpha in vivo.

PMID- 8549064
TI  - Effects of fish oil supplementation on atherosclerosis in different regions of
      the aorta of rabbits with diet-induced hypercholesterolaemia.
AB  - 1. The effects of fish oil supplementation on atherosclerosis in different
      regions of the aorta in rabbits with diet-induced hypercholesterolaemia were
      studied. Control and experimental rabbits were fed a 1% cholesterol-enriched diet
      with or without 10% fish oil supplementation (seven in each group), and were
      killed after 2 weeks of feeding. The ascending, descending and abdominal aortas
      as well as the pulmonary artery were harvested for analyses of prostanoid
      production, malondialdehyde, superoxide dismutase activity and cholesterol
      levels. The tissues from the other seven rabbits of each group were obtained
      after 6 weeks of feeding for the identification of atherosclerotic lesions by a
      Sudan IV stain. 2. The cholesterol-fed rabbits had a significantly higher
      thromboxane B2 production, a lower 6-keto-prostaglandin1 alpha/thromboxane B2
      ratio and a higher malondialdehyde level than the other two groups in the
      ascending and abdominal aortas as well as the pulmonary artery; this finding
      paralleled the severity of atherosclerotic lesions. These manifestations were
      most prominent in the ascending aorta. The fish oil-supplemented rabbits had the
      most beneficial aortic prostanoid production, attenuated lipid peroxidation and
      significantly suppressed atherosclerosis. 3. These results suggest that a high
      cholesterol diet induces more atherosclerotic lesions, especially on the
      ascending aorta, in rabbits. A fish oil supplement favours prostanoid production
      and attenuates lipid peroxidation on all four regions of the great arteries, thus
      suppressing atherosclerosis in diet-induced hypercholesterolaemic rabbits.

PMID- 8549065
TI  - Clinical remission is associated with restoration of normal high-density
      lipoprotein cholesterol levels in children with malignancies.
AB  - 1. Serum lipids and lipoprotein profiles were determined in children affected by
      different types of malignancies (leukaemias or lymphomas and solid tumours) both
      before any treatment and after remission of the disease following chemical or
      surgical therapy. 2. At the time of diagnosis, children bearing tumours showed
      hypertriglyceridaemia and reduced concentrations of plasma high-density
      lipoprotein cholesterol levels, the decrease being particularly prominent in
      patients with haematological tumours. Children bearing solid tumours displayed an
      increase of total cholesterol, while those with haematological cancer showed
      decreased phospholipid levels; low-density lipoprotein cholesterol in neoplastic
      patients was not significantly different from control values. High
      triacylglycerol and low high-density lipoprotein cholesterol levels were also
      evident in cancer patients divided according to age into three groups (0-5, 6-10
      and 11-15 years) when compared with age-matched control subjects. Similarly, high
      triacylglycerol and low high-density lipoprotein cholesterol levels were also
      observed in both male and female children when patients were divided according to
      sex and compared with corresponding controls. 3. Clinical remission after therapy
      was accompanied by an increase of high-density lipoprotein cholesterol levels
      compared with values observed at diagnosis. In contrast, post-treatment levels of
      triacylglycerol were higher than those observed before therapy. These results
      support the hypothesis that alterations of high-density lipoprotein cholesterol
      levels may be related, at least in part, to the rate of tumour growth, while
      modifications of triacylglycerol levels may be mediated by different mechanisms.

PMID- 8549066
TI  - Effects of different lipoproteins on the proliferative response of interleukin-2
      activated T lymphocytes and large granular lymphocytes.
AB  - 1. T lymphocytes and large granular lymphocytes internalized chylomicrons, very
      low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and
      acetyl modified low-density lipoprotein through different receptors as assessed
      by flow cytometry. The observed internalization ranged from 8% to 20%. 2. All
      lipoproteins induced proliferative responses in T lymphocytes and large granular
      lymphocytes at optimum concentrations (40 micrograms of protein/ml for all
      lipoproteins except high-density lipoprotein). Chylomicrons, very low-density
      lipoprotein and low-density lipoprotein increased T-lymphocyte proliferative
      response by fourfold while inducing respectively a seven-, nine- and sevenfold
      increment in large granular lymphocytes. Similarly, high-density lipoprotein and
      acetyl modified low-density lipoprotein respectively induced a nine- and
      sevenfold increment in T cells and a 17- and eightfold increment in large
      granular lymphocyte proliferative response. 3. Both cell types internalized more
      lipoprotein when they were stimulated with interleukin 2. Chylomicrons and low
      density lipoprotein internalization was increased threefold and very low-density
      lipoprotein internalization twofold, while high-density lipoprotein
      internalization was unchanged in both cell types. Acetyl modified low-density
      lipoprotein internalization was fourfold higher in large granular lymphocytes
      only. 4. The proliferative response of interleukin-2 stimulated cells was
      different from that of unstimulated cells. Chylomicrons and very low-density
      lipoprotein induced a sixfold increment in T-cell proliferative response but only
      a fourfold increment in large granular lymphocytes. Low-density lipoprotein and
      acetyl modified low-density lipoprotein induced respectively a sevenfold and
      eightfold increment in T cells and a eightfold and threefold increment in large
      granular lymphocyte proliferative response. High-density lipoprotein did not
      affect T-lymphocyte proliferative response while inducing a twofold increase in
      large granular lymphocytes. 5. Lipoproteins are important in the proliferative
      response of unstimulated and interleukin-2-stimulated cells.

PMID- 8549067
TI  - Intracolonic release in vivo of interleukin-1 beta in chronic ulcerative colitis.
AB  - 1. To investigate the role of interleukin-1 beta in chronic ulcerative colitis,
      we quantified interleukin-1 beta steady-state release into the colonic lumen. 2.
      We studied 26 patients with untreated chronic ulcerative colitis and seven
      patients with irritable bowel syndrome who served as disease controls. In seven
      ulcerative colitis patients, the disease was inactive and in 19 it was mild to
      moderately active, according to clinical and colonoscopic criteria. Seven
      patients with active colitis were studied before and after 4 weeks of treatment
      with oral 5-aminosalicylic acid. 3. Colonic perfusions were performed using a
      double-lumen technique. An isotonic solution was continuously infused 50 cm from
      the anal verge at 5 ml/min, and was recovered 30 cm distally by siphonage.
      Interleukin-1 beta was measured by ELISA, polymorphonuclear elastase by
      immunoactivation and leukotriene B4 by specific RIA. 4. All control patients and
      five out of seven patients with inactive colitis had undetectable interleukin-1
      beta release. In active colitis, the release of interleukin-1 beta was detected
      in 17 out of 19 patients (median 500 pg/min, interquartiles 270-1582 pg/min, P <
      0.01 compared with control subjects and patients with inactive colitis). Elastase
      and leukotriene B4 release were also significantly increased in active colitis
      compared with inactive colitis and controls. Leukotriene B4 release was similar
      in inactive colitis and controls, whereas elastase release was higher in inactive
      colitis than in controls. Five out of seven patients with colitis improved after
      treatment with 5-aminosalicylic acid. In all responder patients, interleukin-1
      beta became undetectable or declined. 5. Our results demonstrate under conditions
      in vivo that active colitis is associated with enhanced interleukin-1 beta
      release into the colonic lumen whereas such release does not occur in remission,
      supporting the concept that ulcerative colitis flare-ups involve increased
      interleukin-1 beta production.

PMID- 8549068
TI  - Atrial natriuretic factor and angiotensin II stimulate nitric oxide release from
      human proximal tubular cells.
AB  - 1. It has been recently reported that angiotensin II can enhance atrial
      natriuretic factor-stimulated cyclic GMP release from brain capillary endothelial
      cells and stimulate directly the release of cyclic GMP by Neuro 2a cells. A
      possible mechanism mediating such cyclic GMP release could be via the production
      of nitric oxide and the resultant stimulation of soluble guanylate cyclase. 2.
      The ability of angiotensin II, atrial natriuretic factor and c(4-23) atrial
      natriuretic factor to stimulate nitric oxide production was investigated in
      primary cultures of human proximal tubular cells. 3. Freshly prepared human
      proximal tubular cells were seeded onto 6-well plates and allowed to reach
      confluence. Cells were then incubated with incremental concentrations of either
      angiotensin II, atrial natriuretic factor or c(4-23) atrial natriuretic factor
      alone for 1, 4, 12 or 24h or in the presence of the nitric oxide synthase
      inhibitor NG-monomethyl-L-arginine. Angiotensin II was also incubated with human
      proximal tubular cells in the presence of the AT1 and AT2 receptor antagonists
      DuP 753 and PD 123319. 4. Incubation of human proximal tubular cells with
      angiotensin II, atrial natriuretic factor or c(4-23) atrial natriuretic factor
      produced a dose- and time-dependent increase in nitric oxide production, which
      was inhibited in the presence of NG-monomethyl-L-arginine. A similar increase in
      nitric oxide production was observed after incubation with atrial natriuretic
      factor or c(4-23) atrial natriuretic factor. 5. The angiotensin-induced increase
      in nitric oxide production was not inhibited in the presence of either the
      angiotensin AT1 or AT2 receptor antagonists DuP 753 or PD 123319. 6. This study
      demonstrates that primary cultures of human proximal tubular cells can be
      stimulated to produce nitric oxide by both atrial natriuretic factor and
      angiotensin II. Furthermore, the atrial natriuretic factor-induced response
      appears to be mediated via the atrial natriuretic factor-C receptor, while the
      angiotensin II-induced response appears to be mediated by a novel, as yet
      unidentified, angiotensin II receptor.

PMID- 8549069
TI  - The urinary F1 activation peptide of human prothrombin is a potent inhibitor of
      calcium oxalate crystallization in undiluted human urine in vitro.
AB  - 1. The urinary F1 activation peptide of prothrombin is the predominant protein
      incorporated into calcium oxalate crystals precipitated from human urine. The aim
      of this study was to examine the effect of pure urinary prothrombin F1 on calcium
      oxalate crystallization in human urine. 2. Urinary prothrombin F1 was purified
      from demineralized calcium oxalate crystals precipitated from human urine, and
      its effects on calcium oxalate crystallization induced by addition of an oxalate
      load were tested in undiluted, ultrafiltered urine from healthy men, at final
      concentrations of 0 to 10 mg/l. 3. Urinary prothrombin F1 did not affect the
      amount of oxalate required to induce crystallization, but the volume of material
      deposited increased in proportion to increasing concentrations of urinary
      prothrombin F1. However, the mean particle size decreased in reverse order: this
      was confirmed by scanning electron microscopy, which showed it to be the result
      of a reduction in crystal aggregation rather than in the size of individual
      crystals. Analysis of 14C-oxalate data revealed a dose-dependent decrease in
      calcium oxalate deposition with an increase in urinary prothrombin F1
      concentration, indicating that the increase in particle volume recorded by the
      Coulter Counter resulted from inclusion of urinary prothrombin F1 into the
      crystalline architecture, rather than increased deposition of calcium oxalate. 4.
      It was concluded that urinary prothrombin F1 may be an important macromolecular
      determinant of stone formation.

PMID- 8549070
TI  - Acute effects of central neuropeptide Y injection on glucose metabolism in fasted
      rats.
AB  - 1. Neuropeptide Y is a potent appetite stimulant and has been found to modulate
      glucose metabolism when given chronically. The acute effects of neuropeptide on
      peripheral glucose handling have not been studied in detail. We have studied the
      acute effects of central nervous system injection of neuropeptide on glucose
      metabolism in vivo in the rat. 2. Rats implanted with chronic cannulae in the
      third cerebral ventricle were injected with either neuropeptide Y or saline and
      peripheral insulin sensitivity was assessed during a hyperinsulinaemic
      euglycaemic clamp. The effect of centrally injected neuropeptide Y on post
      absorptive glucose metabolism was studied using a constant infusion of [6
      3H]glucose. 3. Infusion of neuropeptide Y resulted in a 18% increase in glucose
      requirement during the clamp, suggesting increased peripheral tissue
      responsiveness to insulin. Neuropeptide Y injection in 10h fasted rats increased
      plasma glucose (area under curve 9.9 +/- 0.2 versus 9.1 +/- 0.1 mmol h-1l-1, P <
      0.01), insulin (103 +/- 23 versus 33 +/- 8 pmol/l, P < 0.01, at 30 min) and
      glucagon (5.5 +/- 0.5 versus 3.1 +/- 0.3 pmol/l, P < 0.05, at 30 min). The
      increase in plasma glucose was due to an initial increase in the rate of
      appearance, which peaked between 20 and 30 min after neuropeptide Y infusion;
      over the entire 90 min 16% more glucose entered the systemic circulation in the
      neuropeptide Y-treated rats than in control rats, and the total quantity of
      glucose removed was also greater. 4. Neuropeptide Y in the central nervous system
      influences glucose metabolism by altering secretion of islet hormones, hepatic
      glucose production and the peripheral response to insulin.

PMID- 8549071
TI  - A flow cytometric method to measure shape change of human neutrophils.
AB  - 1. We report a flow cytometric method in which changes in forward angle light
      scatter are shown to correlate with microscopically evaluated shape change in
      stimulated human neutrophils. Neutrophil movement and chemotaxis is
      conventionally measured using Boyden chambers, which is a laborious and exacting
      technique. Microscopic scoring of neutrophil shape change has been shown to
      correlate well with Boyden chamber measurements, and although less laborious,
      still requires manual counting. 2. We now show that measurement of forward angle
      light scatter in a benchtop flow cytometer correlates closely with microscopic
      evaluation of neutrophil shape change in dose-response stimulation experiments
      with leukotriene B4, N-formyl-methionine-leucine-phenylalanine or interleukin-8.
      The relationship between shape change and increased forward angle light scatter
      was confirmed using the fluorescence-activated cell sorter to separate partially
      stimulated neutrophils, followed by reanalysis by flow cytometry and microscopic
      examination. 3. This flow cytometric method provides a convenient, rapid and
      objective measure of neutrophil responses to external stimuli.

PMID- 8549072
TI  - Power spectral analysis of heart rate variability and baroreflex gain.

PMID- 8549073
TI  - On the quantification of heart rate changes in autonomic function tests:
      relations between measures in beats per minute, seconds and dimensionless ratios.
AB  - 1. Disorders of the autonomic nervous system are frequently diagnosed by
      measuring heart rate changes in response to deep-breathing and lying-to-standing
      manoeuvres. The heart rate changes in these manoeuvres are quantified in measures
      using various units, like beats per minute, seconds and dimensionless ratios. 2.
      In the present study we mathematically derived relationships between the measures
      which quantify heart rate changes in beats per minute, seconds and dimensionless
      ratios. The theoretical outcomes were experimentally confirmed by the results of
      the deep-breathing and the lying-to-standing test in 525 healthy and diabetic
      subjects. The measures were found to be non-equivalent, because the mean RR
      interval duration influenced the measures in different ways. 3. It is argued that
      measures in seconds are preferable to measures in beats per minute or ratios,
      because the physiological interpretation of this measure is easier, and the
      sensitivity of measures in seconds is expected to be greater. 4. Finally, we
      recommend that measures of heart rate variation in the deep-breathing and lying
      to-standing manoeuvre are accompanied by information on the mean RR interval
      duration or mean heart rate to allow correct interpretation of the measures.

PMID- 8549075
TI  - Differential effects of a novel non-peptide endothelin receptor antagonist
      (bosentan) in rat liver and vasculature.
AB  - 1. We studied the effects of the non-selective, non-peptide, orally active
      endothelin (ET) receptor antagonist bosentan (Ro 47-0203) on rat hepatic and
      mesenteric vascular membrane 125I-ET-1 binding characteristics in vitro and ex
      vivo (after bosentan by gavage in vivo). 2. Bosentan caused a concentration
      dependent competitive inhibition of 125I-ET-1 binding to female rat mesenteric
      vascular (predominantly ETA receptors) and hepatic (predominantly ETB receptors)
      membranes in vitro and ex vivo. 3. The time course of the inhibition of binding
      ex vivo after administration of bosentan in vivo was 1-4h for mesenteric vascular
      (predominantly ETA receptors) binding and 1-16h for hepatic (predominantly ETB
      receptors) binding. 4. The time course of displacement of 125I-ET-1 binding from
      mesenteric vascular and hepatic membranes by bosentan in vitro was similar. 5.
      Since bosentan is significantly excreted by the liver, the prolonged hepatic 125I
      ET-1 binding by bosentan presumably represents hepatic accumulation of bosentan,
      which may have implications for bosentan antagonizing the actions of ET in the
      liver.

PMID- 8549074
TI  - Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade
      studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody
      and its Fab' fragment.
AB  - 1. Calcitonin gene-related peptide (CGRP) is localized in perivascular sensory
      neurons and is a potent vasodilator. We investigated the utility of
      immunoblockade as an in vivo technique for probing the role of CGRP as an
      endogenous vasodilator. 2. The effects of an anti-CGRP monoclonal antibody (MAb;
      coded C4.19) and its Fab' fragment on CGRP-induced changes in blood pressure and
      skin blood flow were studied in pentobarbitone-anaesthetized rats. Antidromic
      skin vasodilatation in the rat hind paw was measured by laser Doppler fluxmetry.
      3. The dose-response relationship for the hypotensive effect of intravenous rat
      alpha CGRP (r alpha CGRP) was similarly shifted rightward by MAb C4.19 IgG (1
      mg/rat; intravenously) and Fab' fragment (2 mg/rat; intravenously). The C
      terminal fragment of human alpha CGRP (h alpha CGRP8-37) also blocked the
      hypotensive effect of r alpha CGRP. 4. MAb C4.19 Fab' fragment (2 mg/rat;
      intravenously) and h alpha CGRP8-37 (100 nmol/kg; intravenously), but not MAb
      C4.19 IgG (up to 3 mg/rat; intravenously) or normal mouse Fab' fragment (2
      mg/rat; intravenously), blocked the increased skin blood flow response to
      antidromic stimulation of the saphenous nerve. 5. The mean percentage changes in
      skin blood flow parameters due to MAb C4.19 Fab' fragment were significantly
      different from those due to normal mouse Fab' fragment (unpaired t-test; P <
      0.05) but not from those due to h alpha CGRP8-37. 6. The results demonstrate the
      pharmacokinetic advantage of Fab' fragment over IgG for immunoblockade studies in
      vivo and support the role of CGRP in mediating skin vasodilatation.

PMID- 8549077
TI  - Relationship between serum tryptophan and tryptophan metabolite levels after
      tryptophan ingestion in normal subjects and age-related cataract patients.
AB  - 1. Cataract is the single major cause of blindness worldwide; however, the
      reasons for the development of this condition remain unknown. It has been
      suggested that the essential amino acid tryptophan may be implicated in the
      aetiology but definitive evidence has been lacking. 2. The serum levels of
      tryptophan and seven of its metabolites have been measured in both cataract
      patients and control subjects, after administration of tryptophan, in order to
      determine the typical response profile and to discover whether differences could
      be found in tryptophan metabolism in the two groups. 3. Tryptophan, kynurenine,
      kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, 5-hydroxyanthranilic
      acid, 5-hydroxytryptophan and anthranilic acid were measured by HPLC with dual
      electrochemical and programmable wavelength fluorescence detection. Fasting
      cataract patients (n = 42) and control subjects (n = 37) were given an oral dose
      of L-tryptophan and sera were sampled at 0, 1, 2, 4 and 6 h. 4. Statistically
      significant differences in the distribution of data between the two groups were
      observed. The responses of kynurenine and 5-hydroxyanthranilic acid were higher
      in cataract patients, but those of kynurenic acid and total tryptophan were lower
      than in control subjects. No statistically significant differences in free
      tryptophan, anthranilic acid, 3-hydroxyanthranilic acid, xanthurenic acid or 5
      hydroxytryptophan levels were noted. 5. We conclude that there is a major
      subgroup of age-related cataract patients with a dysfunction in the metabolism of
      tryptophan. This may be related to the onset of cataract. The mechanism remains
      to be established but may operate via the action of tryptophan metabolites, such
      as 5-hydroxyanthranilic acid, which become reactive towards protein upon
      oxidation.

PMID- 8549076
TI  - Calf muscle mitochondrial and glycogenolytic ATP synthesis in patients with
      claudication due to peripheral vascular disease analysed using 31P magnetic
      resonance spectroscopy.
AB  - 1. We set out to define abnormalities of oxidative ATP synthesis, cellular proton
      efflux and the efficiency of ATP usage in gastrocnemius muscle of patients with
      claudication due to peripheral vascular disease, using data obtained by 31P
      magnetic resonance spectroscopy during aerobic exercise and recovery. 2. Eleven
      patients with moderate claudication were studied and results were compared with
      25 age-matched control subjects. Changes in pH and phosphocreatine concentration
      during recovery were used to calculate the maximum rate of oxidative ATP
      synthesis (Qmax.) and the capacity of net proton efflux. Changes in pH and
      phosphocreatine concentration were used to estimate rates of non-oxidative and
      (indirectly) oxidative ATP synthesis throughout exercise, taking account of
      abnormalities in proton efflux during exercise. 3. In patients with claudication,
      slow post-exercise phosphocreatine recovery showed a 42 +/- 9% decrease in Qmax.,
      and the slow ADP recovery was consistent with this. pH recovery was slow, showing
      a 77 +/- 9% decrease in the capacity for proton efflux. Both abnormalities are
      compatible with a substantial reduction in muscle blood flow. 4. During exercise,
      increased phosphocreatine depletion and intracellular acidification were a
      consequence of impaired oxidative ATP synthesis and the consequent increase in
      non-oxidative ATP synthesis, compounded by reduced proton efflux. The
      acidification prevented an increase in ADP concentration which could otherwise
      partially compensate for the oxidative defect. All these abnormalities are
      compatible with a reduced muscle blood flow. 5. In addition, initial-exercise
      changes in pH and phosphocreatine concentration implied a 44 +/- 5% reduction in
      'effective muscle mass', necessitating an ATP turnover (per litre of muscle
      water) twice as high for given power output as in control muscle. Some of this is
      probably due to a localized loss of muscle fibres, but the rest appears to
      reflect reduced metabolic efficiency of the muscle. This is not a direct
      consequence of reduced blood flow, and may be related to change in muscle fibre
      type.

PMID- 8549078
TI  - Septic patients in multiple organ failure can oxidize infused glucose, but non
      oxidative disposal (storage) is impaired.
AB  - 1. Patients suffering trauma and sepsis are insulin resistant, but no studies
      have specifically been made of patients suffering multiple organ failure. 2. We
      have studied exogenous glucose utilization in multiple organ failure using a
      combination of the hyperglycaemic glucose clamp and indirect calorimetry to
      quantify glucose utilization in multiple organ failure, partitioning it into
      oxidative and nonoxidative disposal (storage). 3. Fourteen septic patients with
      multiple organ failure were studied. APACHE II (Acute Physiological and Chronic
      Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31
      (median 16). Twenty percent D-glucose was infused and blood glucose was clamped
      at 12 mmol/l for 3 h. The results were compared with those obtained on seven
      healthy control subjects. 4. Glucose utilization and energy expenditure were
      similar in the two groups for the first 90 min of the clamp, after which glucose
      utilization and energy expenditure increased steadily in the control subjects but
      did not change in the patients. Respiratory exchange ratio rose in both groups;
      considered over the whole of the clamp period, respiratory exchange ratio was
      slightly lower in the patients than in the control subjects (P < 0.05) but not at
      any specific time point. Glucose oxidation rose in both groups but non-oxidative
      glucose disposal (storage) rose only in the control subjects. Glucose oxidation
      was slightly lower in the patients (P < 0.05) but not at any specific time point
      and there was no difference between the groups in the amount by which glucose
      oxidation increased. Non-oxidative disposal in the patients fell significantly (P
      < 0.01) over the course of the clamp and was significantly lower than in the
      control subjects (P < 0.01). 5. Growth hormone increased in response to glucose
      infusion in the patients but not in the control subjects. 6. Like patients
      suffering uncomplicated sepsis or trauma, patients with multiple organ failure
      are also insulin resistant. The defect appears to lie in an impairment of the
      ability to store glucose rather than oxidize it, and this may be due in part to
      the increase in growth hormone in patients with multiple organ failure.

PMID- 8549079
TI  - Insulin-like growth factor I is a major fibroblast mitogen produced by primary
      cultures of human airway epithelial cells.
AB  - 1. The ability of airway epithelial cells to produce insulin-like growth factor I
      may be important in the pathogenesis of subepithelial fibrosis observed in the
      airways of patients with asthma. We determined whether human airway epithelial
      cells are capable of producing polypeptide mediators that could induce fibroblast
      proliferative activity, in particular insulin-like growth factor I. 2. We
      examined 12 primary cultures of human airway epithelial cells grown to confluence
      on collagen gel-coated dishes. Using a colorimetric assay based on the uptake and
      subsequent release of Methylene Blue, increased proliferation of human fetal lung
      fibroblasts was detected in conditioned media from airway epithelial cells. The
      median stimulation of fibroblast proliferation was 49.9% (range 25.6-113.3%)
      above control values (observed at 1:2 dilution of media). 3. A neutralizing
      antiserum to insulin-like growth factor I partly inhibited fibroblast
      proliferation induced by epithelial cell conditioned media by 52.2% (49.9-109%; n
      = 5). 4. Radioimmunoassay for insulin-like growth factor I in conditioned media
      demonstrated a median concentration of 54.1 ng/ml (32.4-96.8 ng/ml). 5. Insulin
      like growth factor I mRNA was detected in epithelial cell monolayers by Northern
      blot analysis using an insulin-like growth factor I cDNA probe. 6. The insulin
      like growth factor I gene is expressed in cultured human airway epithelial cells,
      which also secrete insulin-like growth factor I protein. Insulin-like growth
      factor I also accounts for the major mitogenic activity for fibroblasts of
      cultured human epithelial cell conditioned media. Insulin-like growth factor I
      may function in a paracrine manner to modulate fibroblast behaviour and may be
      involved in airway processes, such as those occurring in asthma.

PMID- 8549080
TI  - Effect of ozone exposure on maximal airway narrowing in non-asthmatic and
      asthmatic subjects.
AB  - 1. Ozone is a major constituent of air pollution in the summer. Epidemiological
      studies have demonstrated that there is an increase in hospital admissions for
      respiratory diseases 1 day after peak levels of ambient ozone. This may be due to
      an increase in the responsiveness of the airways to bronchoconstrictor stimuli.
      2. In the present study we therefore studied the effect of a controlled exposure
      to ozone on the maximal degree of airway narrowing to a non-specific
      bronchoconstrictor, methacholine, 12 h after exposure. Both non-asthmatic and
      mild-asthmatic volunteers were exposed to ozone. 3. The study had a single blind
      design. Experimental exposures were to filtered air, 0.40 ppm ozone and filtered
      air respectively, at 1-week intervals. The duration of each exposure was 2 h with
      alternating periods of 15 min rest and exercise. At 12 h after exposure,
      methacholine inhalation challenge tests and sputum induction were performed. 4.
      Twelve hours after exposure to ozone there was a significant increase in the
      maximal degree of airway narrowing to methacholine (P < 0.02) compared with
      exposure to air, in non-asthmatic as well as asthmatic subjects. These
      physiological changes were accompanied by a significant rise in the percentage of
      neutrophils in induced sputum (P < 0.02). All changes had returned to baseline
      values 1 week after exposure to ozone. 5. Exposure to ozone causes a transient
      increase in the maximal degree of airway narrowing to methacholine in both non
      asthmatic and asthmatic subjects. These laboratory results, obtained using
      relatively high ozone exposure in carefully selected subjects, might provide an
      explanation for the temporal relationship between ambient ozone levels and
      hospital admissions for asthma.

PMID- 8549081
TI  - The cost of breathing in stable chronic obstructive pulmonary disease.
AB  - 1. The hypermetabolism frequently observed at rest in patients with chronic
      obstructive pulmonary disease has been attributed to a high cost of breathing.
      However, measurement of the cost of breathing by the usual hyperventilation
      procedure is fraught with methodological problems. The purpose of this study was
      to measure more directly the cost of breathing in a group of ambulatory patients
      with stable chronic obstructive pulmonary disease. 2. The cost of breathing was
      calculated as the difference in oxygen consumption measured by indirect
      calorimetry between spontaneous breathing and noninvasive mechanical ventilation.
      Inspiratory muscle rest was achieved by negative or positive pressure ventilation
      and assessed by the recording of surface electromyograms of the diaphragm and
      parasternal intercostal muscles. 3. Seven tests were performed in six ambulatory
      patients with stable chronic obstructive pulmonary disease, four tests using
      positive pressure ventilation and three with negative pressure ventilation.
      During mechanical ventilation, the electromyographic activity of the diaphragm
      decreased by 70 +/- 22%, while that of the parasternals was suppressed in four
      tests, and remained unchanged in three. However, oxygen consumption was only 1.6
      +/- 6.2% lower during mechanical ventilation. 4. The cost of breathing measured
      in this study was therefore much lower than previously published values. Stress
      was not likely to influence the results, as both the heart rate and plasma
      catecholamines did not change between spontaneous breathing and mechanical
      ventilation. These results suggest that the cost of breathing in ambulatory
      patients with stable chronic obstructive pulmonary disease may be lower than
      previously estimated.

PMID- 8549082
TI  - Intravenous magnesium sulphate relieves migraine attacks in patients with low
      serum ionized magnesium levels: a pilot study.
AB  - 1. We tested the hypothesis that patients with an acute attack of migraine
      headache and low serum levels (< 0.54 mmol/l) of ionized magnesium are more
      likely to respond to an intravenous infusion of magnesium sulphate (MgSO4) than
      patients with higher serum ionized magnesium levels. 2. Serum ionized magnesium
      levels were drawn immediately before infusion of 1 g of MgSO4 in 40 consecutive
      patients with an acute migraine headache. 3. Pain reduction of 50% or more as
      measured on a headache intensity verbal scale of 1 to 10, occurred within 15 min
      of infusion in 35 patients. In 21 patients, at least this degree of improvement
      or complete relief persisted for 24h or more. Pain relief lasted at least 24h in
      18 of 21 patients (86%) with serum ionized magnesium levels below 0.54 mmol/l,
      and in 3 of 19 patients (16%) with ionized magnesium levels at or above 0.54
      mmol/l (P < 0.001). Mean ionized magnesium levels in patients with relief lasting
      for at least 24h were significantly lower than in patients with no relief or
      brief relief (P < 0.01). 4. Measurement of serum ionized magnesium levels may be
      useful in identifying patients with migraine headaches who may respond to an
      intravenous infusion of MgSO4.

PMID- 8549083
TI  - Low selenium status in the elderly influences thyroid hormones.
AB  - 1. Iodothyronine 5'-deiodinase, which is mainly responsible for peripheral
      triiodothyronine (T3) production, has recently been demonstrated to be a selenium
      containing enzyme. In the elderly, reduced peripheral conversion of thyroxine
      (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum
      selenium and erythrocyte glutathione peroxidase (as indices of selenium status),
      thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid
      subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid
      hormone levels induced by acute or chronic diseases or calorie restriction. The
      subjects were subdivided into three age groups. To avoid conditions of under
      nutrition or malnutrition, dietary records were obtained for a sample of 24
      subjects, randomly selected and representative of the whole population for age
      and sex. 3. In order to properly assess the influence of selenium status on
      iodothyronine 5'-deiodinase type I activity, a double-blind placebo-controlled
      trial was also carried out on 36 elderly subjects, resident at a privately owned
      nursing home. 4. In the free-living population, a progressive reduction of the
      T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte
      glutathione peroxidase activity was observed with advancing age. A highly
      significant linear correlation between T4, T3/T4 and selenium was observed in the
      population as a whole (for T4, R = -0.312, P < 0.002; for T3/T4 ratio, R = 0.32,
      P < 0.01) and in older subjects (for T4, R = -0.40, P < 0.05; for T3/T4 ratio, R
      = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled
      trial was a significant improvement of selenium indices and a decrease in the T4
      level in selenium-treated subjects; serum selenium, erythrocyte glutathione
      peroxidase activity and thyroid hormones did not change in placebo-treated
      subjects. 6. We concluded that selenium status influences thyroid hormones in the
      elderly, mainly modulating T4 levels.

PMID- 8549084
TI  - Metabolic acidosis does not contribute to chronic renal injury in the rat.
AB  - 1. Metabolic acidosis invariably accompanies chronic renal failure, and short
      periods of metabolic acidosis cause renal growth and proteinuria in normal rats.
      Rates of ammoniagenesis are increased in chronic renal failure, and it has been
      suggested that this contributes to disease progression. This study assessed (i)
      whether prolonged acidosis causes chronic renal injury in the normal kidney and
      (ii) whether abrogation of acidosis slows disease progression in the remnant
      kidney. 2. Metabolic acidosis was induced in normal rats by dietary hydrochloric
      acid. Urinary excretion of total protein, lysozyme and albumin increased, peaking
      at week 8 but returning to baseline by week 14. At killing after 14 weeks, kidney
      weights, glomerular filtration rates and serum creatinine were the same in both
      groups, but kidney/body weight and kidney/heart weight ratios were greater in the
      acidotic group. All kidneys were normal by light microscopy. 3. Rats subjected to
      five-sixths nephrectomy were given sufficient dietary bicarbonate to abolish
      uraemic acidosis, and their outcome was compared with that of non-alkalinized
      remnants (controls). Proteinuria, glomerular filtration rates, blood pressure,
      histological injury and time to the development of terminal uraemia were no
      better in bicarbonate-supplemented animals than in controls. 4. These data
      demonstrate that metabolic acidosis neither causes nor exacerbates chronic renal
      injury. We conclude that the treatment of uraemic acidosis is unlikely to
      influence disease progression in patients with chronic renal failure.

PMID- 8549085
TI  - Comparison of bio-impedance spectroscopy and multi-frequency bio-impedance
      analysis for the assessment of extracellular and total body water in surgical
      patients.
AB  - 1. Measurements of extracellular and total body water provide useful information
      on the nutritional status of surgical patients and may be estimated from whole
      body bio-impedance measurements at different frequencies. 2. Resistance and
      reactance were measured at 50 frequencies from 5kHz to 1MHz in 29 surgical
      patients (17 males, 12 females) with a wide range of extracellular to total body
      water ratios. 3. A fit to the spectrum of reactance versus resistance data gave
      predicted resistances at frequencies zero and infinity. Values of extracellular
      and total body water determined by this bio-impedance spectroscopy technique were
      regressed against values obtained from radioisotope dilution. The standard errors
      of the estimate were 1.8931 and 3.2591 respectively. 4. Resistance indices
      (height2/resistance) at selected frequencies gave the highest correlations with
      extracellular and total body water at 5kHz and 200kHz respectively, and
      prediction equations derived from multiple stepwise regressions also showed these
      to be the optimum frequencies. The standard errors of the estimate for this multi
      frequency bio-impedance analysis method were 1.9371 and 2.6061 for extracellular
      and total body water respectively. 5. To assess the ability of the two methods to
      measure changes in extracellular and total body water, reproducibility was
      assessed from repeat measurements 10 min apart in a subgroup of 15 patients. Bio
      impedance spectroscopy gave mean coefficients of variation for extracellular and
      total body water of 0.9% and 3.0% respectively. For multi-frequency bio-impedance
      analysis the corresponding coefficients of variation were 0.9% and 0.6%. 6. It is
      concluded that a simple impedance analyser operating at only two frequencies
      compares favourably with the more complex spectroscopy technique for the
      determination of extracellular and total body water in surgical patients.

PMID- 8549087
TI  - Chondrocalcinosis: sonographic study of the knee.

PMID- 8549086
TI  - Apoptosis and its association with autoimmunity.

PMID- 8549088
TI  - Prognostic factors for the outcome of methotrexate treatment in rheumatoid
      arthritis.

PMID- 8549090
TI  - Evaluation of the International Study Group for Behcet's Disease Criteria in
      Brazilian patients.

PMID- 8549089
TI  - Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and
      erythropoiesis in anaemia of chronic disease.

PMID- 8549091
TI  - A double-blind controlled study comparing sulphasalazine with placebo in
      rheumatoid factor (RF)-negative rheumatoid arthritis.

PMID- 8549092
TI  - The clinical and immunological effects of cyclosporin A on patients with
      rheumatoid arthritis.

PMID- 8549093
TI  - Experience with low-dose methotrexate: toxicity, tolerability and effect on
      conventional patterns of drug therapy for inflammatory arthritis.

PMID- 8549094
TI  - Erosive polyarthritis as presenting manifestation of Wegener's granulomatosis.

PMID- 8549095
TI  - Coexisting rheumatoid arthritis and ankylosing spondylitis discussion of 3 cases
      with review of the literature.

PMID- 8549096
TI  - The effect of auranofin and sulphasalazine therapy on circulating levels of
      interleukin 6 in rheumatoid arthritis patients.

PMID- 8549098
TI  - Sjogren's syndrome and hepatitis C virus infection.

PMID- 8549097
TI  - Does methotrexate affect serum level of IgA-alpha-1 antitrypsin complex in early
      rheumatoid arthritis?

PMID- 8549099
TI  - Pulmonary malignancy associated with granulomatous vasculitis in the maxillary
      sinus.

PMID- 8549100
TI  - Intermittent polyarthritis due to propylthiouracil.

PMID- 8549101
TI  - Mutilating rheumatoid arthritis associated with sarcoidosis: a case report.

PMID- 8549102
TI  - Arthritis in Israeli spotted fever.

PMID- 8549103
TI  - Progressive diaphyseal dysplasia masquerading as shoulder capsulitis in an adult.

PMID- 8549104
TI  - Late onset muscular dystrophy proximal myopathy and recurrent falls in the
      elderly.

PMID- 8549105
TI  - Systemic lupus erythematosus and eosinophilic fasciitis: an unusual association.

PMID- 8549106
TI  - Palmar rheumatoid nodulosis of the fingers.

PMID- 8549107
TI  - Laptop meralgia.

PMID- 8549109
TI  - British Diabetic Association's Education and Professional Care Section annual
      conference and Medical and Scientific Section autumn meeting. October 4-6, 1995.
      Abstracts.

PMID- 8549108
TI  - Treatment of osteoporosis of rheumatoid arthritis.

PMID- 8549110
TI  - The 13th International Symposium of the World Association of Veterinary
      Microbiologists, Immunologists and Specialists in Infectious Diseases Perugia,
      Mantova, Italy 2-7 October 1994.

PMID- 8549111
TI  - Choice of the optimal method for the isolation of Salmonella from meat- and bone
      powder designed for industrial feed mixtures.
AB  - The purpose of this paper was (1) comparison of four multi-step methods used for
      Salmonella isolation from meat- and bone powder; (2) elaboration of a new
      sensitive method of Salmonella isolation from this product; (3) evaluation of a
      new solid selective medium (BxLH) described by the authors for Salmonella
      isolation in comparison to brilliant green agar (BGE) according to Edel and
      Kampelmacher. The study was carried out on 173 meat- and bone powder samples
      naturally contaminated with Salmonella oranienburg. The samples were examined for
      the Salmonella presence by means of four compared methods (Methods 1 to 4). The
      new method of isolation proposed by the authors (Method 3) proved to be the most
      effective among all compared for Salmonella recovery. It seems that the
      superiority of Method 3 in comparison to the other applied was a result of, (1)
      homogenization of the investigated samples in distilled water before
      preincubation followed by maintenance at room temperature for 2-4 h; (2) the use
      of a new selective BxLH agar; (3) the use of multiple plating after selective
      enrichment. The BxLH medium was shown to be more suitable for Salmonella
      isolation than BGE agar because of more efficient inhibition of other bacterial
      growth with simultaneously abundant growth of the Salmonella organisms. The
      additional advantage offered by BxLH agar was the fact that lactose-positive
      salmonellas grow as typical representatives of this genus. This enables their
      identification, in contrast to the situation when lactose containing media are
      used, where the colonies of such salmonellas are similar to the colonies of, for
      example, Escherichia coli.

PMID- 8549112
TI  - Studies on the suitability of alpha-hybrid interferon application in cattle.
AB  - Twelve cattle with body wts ranging from 100 to 250 kg were treated using various
      doses and routes for four days with an E. coli derived alpha-hybrid interferon.
      The lowest parenteral doses (10(4) units per kg body wt) and the orally
      administered interferon did not lead to any disturbances, whereas the higher
      dosages led to marked changes in body temperature, pulse and respiration rates.
      Animals with the highest dose (10(8) units per kg body wt) became extremely
      distressed. The blood picture showed distinct changes, with very low leukocyte
      counts during treatment, which took weeks to recover. It is suggested that the
      dosages that did not lead to clinical symptoms are best suited for prophylactic
      or therapeutic purposes.

PMID- 8549113
TI  - Minute virus of mice (MVM) nucleic acid production in susceptible and resistant
      strains of mice and F1 hybrids.
AB  - Susceptibility of neonatal mice to the lethal effects of the virulent allotropic
      variant of minute virus of mice is controlled by host genotype. We quantitated
      MVM-DNA production in resistant C57BL/6 (B6), susceptible C3H/He (H), and (B6 x
      H) F1 (F1) hybrid mice. Total DNA extracted from six organs of infected mice on
      post inoculation days (PID) 3, 5, 7, and 9 was analyzed by dot blot and Southern
      blot assays. 7 to 100-fold more viral DNA was produced in H mice than in B6 mice
      on PID 7 depending on the organ and F1 mice phenotypically resembled B6 mice.
      Southern blot analysis of DNA extracted from infected mice on PID 7 showed a
      prominent single-stranded band (5 kb, virion DNA) and a faint replicative form (5
      kb, double-stranded) in all strains of mice. Total RNA extracted from the organs
      of B6, H, and F1 mice was analyzed by Northern blot. Viral mRNA production was
      generally below detection limits. In kidneys, hearts, and intestines of some H
      mice on PID 7, however, a 1.9 kb transcript was detected, smaller than
      transcripts for R1, R2 or R3. This study confirms that susceptibility to lethal
      MVMi infection correlates with upregulation of MVM DNA production, a recessive
      trait, and perhaps with the production of a novel 1.9 kb transcript.

PMID- 8549114
TI  - Foot-and-mouth disease. Challenge of cattle after multiple vaccinations.
AB  - Four groups of six cattle were vaccinated from two to five times at 6 month
      intervals with two different trivalent FMD vaccines licensed in the given year.
      The FMDV type A strains in the vaccines designated A5F and A5B were closely
      related. Three months after the last vaccination the cattle were challenged by
      contact with animals inoculated with the original field strain A5B. The
      inoculated animals developed typical FMD symptoms with vesicles in the mouth and
      on the feet. Those cattle which had received vaccines that did not contain strain
      A5B also became severely sick, even after five vaccinations. Animals vaccinated
      twice with type B containing vaccine were also not completely protected. A safe
      protection can obviously only be achieved for fairly short periods of time if
      vaccine and challenge strain are homologous. It is proposed to change the rules
      of licensing, to speed up the procedure to vaccinate in cases of outbreaks. The
      need for further research, especially into improving vaccines, is stressed.

PMID- 8549115
TI  - Immune responses to the capsular polysaccharide of Mycoplasma dispar in calves
      and mice.
AB  - Humoral and cell-mediated immune responses to the capsular polysaccharide (CPS)
      of M. dispar and polygalacturonic acid (pGaIU--a structurally similar
      polysaccharide) were investigated in calves experimentally infected with
      Mycoplasma dispar and in mice immunized with CPS or pGaIU. Sera, tracheobronchial
      lavage and nasal fluids, collected before and after infection in calves, were
      checked for the presence of anti-CPS and anti-pGaIU antibodies. The sera from
      mice injected with CPS or pGaIU were checked for different classes of anti-CPS
      and anti-pGaIU antibodies. Peripheral blood lymphocytes from calves and splenic
      lymphocytes from mice were monitored for specific proliferative responses to CPS
      and pGaIU. At about 2 weeks post-infection, anti-CPS IgM response in serum, anti
      CPS and anti-pGaIU IgM and IgA response in lavage fluid and lymphocyte
      proliferative response was seen in the calves. Mice immunized with CPS and pGaIU
      gave exclusively IgM responses. No secondary response was seen in mice immunized
      with CPS in contrast to mice immunized with pGaIU. Antibodies cross-reactive with
      pGaIU were present in the sera of CPS-immunized mice but antibodies cross
      reactive with CPS were not found in pGaIU-immunized mice. No significant
      blastogenic response was shown by mouse splenocytes to CPS or pGaIU.

PMID- 8549116
TI  - A Dot enzyme linked immunosorbent assay (Dot ELISA): comparison with standard
      fluorescent antibody test (FAT) for the diagnosis of rabies in animals.
AB  - A modified enzyme linked immunosorbent assay (Dot ELISA) is described for visual
      detection of rabies antigen in animals. The test materials were dotted onto the
      nitrocellulose paper and allowed to react with rabies antiserum. The bound
      antigen--anti-body were reacted with a peroxidase conjugated antirabbit
      immunoglobulin. Positive reactions were easily visualized as brown dots after
      enzyme degradation of the substrate. A total of 400 specimens from various
      geographical locations were tested with the dot ELISA technique, and also with
      the fluorescent antibody test (FAT), which was used as a reference method. The
      concordance between the two tests was 95.25%. The dot ELISA may have potential
      applications as a rapid, simple and economical field test in the diagnosis of
      rabies.

PMID- 8549117
TI  - Immunohistochemical analysis of pseudorabies virus spread through neurons
      innervating the eyeball.
AB  - Pseudorabies virus (PRV) was inoculated intraocularly into BALB/c mice, and the
      distribution pattern of cells positive for several neurotransmitters and viral
      antigens in the eyeball, trigeminal nerve ganglia, and superior cervical ganglia
      was examined immunohistochemically to clarify the neural route of the virus
      spread. In the eyeball, substance P (SP)- and calcitonin gene-related peptide
      (CGRP)-positive cells were detected in the ipsilateral iris and ciliary body,
      neuropeptide tyrosine (NPY)-positive cells were detected in the choloid membrane,
      and tyrosine hydroxylase (TH)-positive cells were detected in the ipsilateral
      inner nuclear layer of the retina; all these cells contained viral antigens. In
      the superior cervical ganglia, viral antigen-positive cells containing TH or NPY
      were found at bilateral sites. In the trigeminal nerve ganglia, viral antigen
      positive cells containing SP or CGRP were found at bilateral sites. These
      findings indicated that the SP- and CGRP-positive ganglion cells of the
      trigeminal nerve ganglia innervating the iris or ciliary body, and the NPY
      positive ganglion cells of the superior cervical ganglia innervating the iris,
      ciliary body, and choroid membrane served as the route for the virus spread.
      These findings also suggested that dopaminergic neurons, such as the TH-positive
      retinal cells and TH-positive ganglion cells of the superior cervical ganglia,
      served as the route for virus spread.

PMID- 8549118
TI  - Plasmid profile and phage type of Salmonella typhimurium strains encountered in
      different regions of India.
AB  - A total of 190 Salmonella typhimurium strains encountered in different parts of
      India were characterized on the basis of plasmid profile, phage type and
      antimicrobial resistance pattern. Recent trends in the epidemiology of R-plasmids
      were also studied. The majority of S. typhimurium strains (90.5%) were untypable
      by phage typing. Only 18 strains (9.5%) were phage typable. The phage untypable
      strains isolated from northern (57) central (65), and southern (50) regions of
      India could be subgrouped into 24, 12 and 16 different plasmid profiles
      respectively. Heterogeneity was the prominent feature although most of the
      plasmid profiles were related among strains isolated from particular place. A
      great diversity among small plasmids (2.7-8.3 kb) made subgrouping of majority
      strains (71%) with R-pattern ApCmKmSmSuTcTp possible. Conjugation studies and
      plasmid profile analysis of transconjugants revealed all the strains to harbour
      non conjugative non-auto transmissible plasmids with the exception of 7.2 and 2.7
      kb plasmids which were not mobilizable.

PMID- 8549119
TI  - Pediatric parenteral nutrition mixtures design program: validity and stability
      study.
AB  - The formulation and elaboration of a correct parenteral nutrition (PN) in infancy
      requires the use of many parameters, the realization of complicated mathematical
      calculations, and repeated and individualized adjustments of the final
      constituents. The use of computer programs in the confection of PN has simplified
      the whole process, but, to our understanding, the programs being used at the
      moment lack the flexibility needed to generalize its use in the pediatric age.
      The aim of this work is to present a new computer program able to make up
      complete pediatric units of PN by itself, which follow the nutritional
      requirements and the marketed preparations established for each clinical
      situation. The program provides, automatically, standard amounts for each
      nutrient, according to age, water needs, and route of administration. The program
      turns these amounts, which can be modified before or after knowing the final
      composition, into milliliters of each commercial product and provides a complete
      analysis of the PN solution. It is also possible to adapt the basic configuration
      of the program to the needs of each patient, modifying the nutritional
      requirements and the products that the program will use. In order to assess the
      validity of the program, we made up a series of PN solutions, for a simulated
      sample of patients, which represented different clinical situations and age
      groups. We analyzed the composition of the mixtures and its physical-chemical
      stability. No problems in the PN solutions generated by the program when using
      our standard configuration were found. A study of reproducibility was carried out
      and no difficulties of execution, errors, or differences in the composition of
      the PN solutions designed by the different physicians were found. Average time
      needed for the design of a PN was less than 5 min. The use of computer programs
      in the design of mixtures of PN reduces errors and time, allowing a better use of
      this technique of nutritional support.

PMID- 8549120
TI  - Effects of digital filtering on the parameters of sinusoidal tracking eye
      movements.
AB  - In the present study linear nonrecursive (FIR) filters designed with the Hamming
      window and hybrid median filters were examined in connection with computer
      analysis of sinusoidal tracking eye movements. It is important that digital
      filters which do not distort sensitive properties of eye movement signals are
      employed in order to prevent changes caused by too strict filtering in average
      parameter values of eye movement signals, indicators of some otoneurological
      disorders. It turned out that within reasonable limits these filters are valid in
      filtering of sinusoidal tracking eye movement signals.

PMID- 8549121
TI  - Automated grading of venous beading.
AB  - The degree of venous beading in ocular fundus images has been shown to be a more
      powerful predictor of conversion to proliferative diabetic retinopathy than any
      other type of retinal abnormality. Further, the degree of venous beading has been
      shown to be well correlated with disease progression. An algorithm for automated
      grading of venous beading in digitized ocular fundus images is described.
      Thresholding is used to extract a rough silhouette of the vein. Morphological
      closing is used to fill any holes in the silhouette arising from either the
      central light reflex or noise. The silhouette is then "thinned" to find vein
      centerlines. Each centerline is partitioned into fixed-length segments of 32
      pixels. Vein diameters are measured as a function of distance along each segment
      with the aid of the local centerline orientations. The resulting diameter data
      are then interpolated and resampled to generate diameter data at constant
      sampling intervals. A fast Fourier transform is performed on the resulting data
      to determine the magnitude spectrum of vein segment diameter. A venous beading
      index is calculated from the distribution of vein diameter frequency components.
      Performance of the new algorithm is compared to the currently accepted clinical
      practice of manual grading in a pilot clinical study of 51 subjects. The
      algorithm is seen to perform well.

PMID- 8549123
TI  - A neural network approach for the determination of interhospital transport mode.
AB  - We report on the construction of neural networks for determining whether
      pediatric patients requiring transport to a tertiary care center should be moved
      by air or by ground. The networks were based on the functional-link net
      architecture. In two experiments, feedforward supervised-learning neural nets
      were trained with examples of an expert's decisions and then were used in a
      consulting mode to provide advice on cases not previously encountered. Training
      and validation were performed by a combination of the k-fold cross-validation and
      leaving-one-out sampling methods. Use of the functional-link net rather than the
      customary backpropagation net enabled us to carry out the training with fairly
      large amounts of data in realistically short time periods. In the first
      experiment, capillary refill, skin color, and stridor were consistently the input
      variables that were most strongly associated with the decision output. In both
      experiments, the networks were validated by comparing their performance
      retrospectively against the determination of an expert pediatric transport
      physician. The network was trained based on the expert's opinion about the
      correct mode of transport for each case with error rates of less than 10(-5).

PMID- 8549122
TI  - Classification of arrhythmic events in ambulatory electrocardiogram, using
      artificial neural networks.
AB  - We propose artificial neural networks (ANN) for ambulatory ECG arrhythmic event
      classification, and we compare them with some traditional classifiers (TC). Among
      them, the one based on the median method (heuristic algorithm) was chosen and
      taken as a quality reference in this study, while a back propagation based
      classifier, designed as an autoassociator for its peculiar capability of
      rejecting unknown patterns, was examined. Two tests were performed: the first to
      discriminate normal vs ventricular beats and the second to distinguish among
      three classes of arrhythmic events. The results show that the ANN approach is
      more reliable than the traditional classifiers in discriminating among many
      classes of arrhythmic events: 98% by ANN vs 99% by a TC for correctly classified
      normal beats, 98% by ANN vs 96% by TC for correctly classified ventricular
      ectopic beats, 96% by ANN vs 59% by TC for correctly classified supraventricular
      ectopic beats, and 83% by ANN vs 86% by median method for correctly classified
      aberrated atrial premature beats. This paper also tackles the problem of the
      management of classification uncertainty. Two concurrent uncertainty criteria
      have been introduced, to reduce the classification error of the unknown
      ventricular and supraventricular arrhythmic beats respectively. The error in
      ventricular beats case was kept close to 0% in average and for supraventricular
      beats was kept at 35% in average. So we can state that the ANN approach is
      powerful in classifying beats represented in the training set and that it manages
      the uncertainty in such a way as to reduce, in any case, the global error
      percentage.

PMID- 8549124
TI  - Contact allergens in toothpastes and a review of their hypersensitivity.
AB  - The present study summarizes information on toothpaste composition as supplied by
      the manufacturers. The survey covered 48 items, virtually all toothpastes offered
      for sale in Finland. It was concluded that the toothpastes are not entirely safe
      to use, because almost 50% of the products studied contained a total of some 30
      compounds widely recognized as allergens. According to the literature, the most
      common allergens in toothpastes are flavours (e.g., cinnamic aldehyde, cinnamon
      oil and peppermint) and preservatives. Symptoms include stomatitis, cheilitis,
      glossitis, gingivitis, perioral dermatitis and immediate hypersensitivity.

PMID- 8549125
TI  - Rapid increase in skin problems among dental technician trainees working with
      acrylates.
AB  - A panel of trainees at The Danish School of Dental Technicians was asked to fill
      in questionnaires 2X a year, to elucidate whether the prevalence of skin problems
      on their hands increased during the study and to compare the results to the
      general population. At the beginning of the study, trainees had a prevalence of
      skin problems not statistically significantly different from that in the general
      population. 8 months later, an increase of 23% in the prevalence was observed.
      Compared to the general population the standardized prevalence ratio (SPR)
      increased to 4.78, and compared to dental technicians at work, an SPR of 0.71 was
      found after 1 year of study. Very few trainees experienced relief in symptoms
      during the 1st year of study (5%), whereas 33% developed worse symptoms. The
      results demonstrate that trainees shortly after beginning their education have
      the same very high magnitude of skin problems as dental technicians at work.
      Trainees were exposed to acrylates more extensively than dental technicians. It
      is far from acceptable that this educational experience involves such a great
      risk to individuals with no experience or knowledge of the hazards of their
      occupational environment. Preventive actions are called for, e.g., increased use
      of encapsulated systems, use of gloves with a well documented protective effect
      and mandatory courses on the hazardous effects of dental materials.

PMID- 8549126
TI  - Occupational contact dermatitis in bakers, confectioners and cooks. A population
      based study.
AB  - A population-based study was performed to investigate incidence rates of
      occupational skin disease (OSD) in bakers, confectioners and cooks, as well as
      the role of endogenous and exogenous risk factors. In North Bavaria, all closed
      cases of OSD were recorded systematically in a 3-year period and the total number
      of employees in the food industry was known over the same period of time.
      Incidence rates of OSD and relative risks of atopic skin diathesis (AD) and
      respiratory atopy (RA) were calculated. The overall incidence rate (I) of OSD (in
      3 years per 10.000 employees) was 67 (95% CI 58;76) in these occupations. Bakers
      had a higher risk of OSD, with an incidence of 191 (95% CI 156;226) compared to
      confectioners with I = 84 (95% CI 55;113) and cooks I = 34 (95% CI 28;40).
      Incidence rates were sex- and age-related. Females developed OSD with an
      incidence rate of 74 (95% CI 64;84) compared to males with I = 58 (95% CI 48;70).
      OSD occurred mostly between the ages of 15 and 24 years. Irritant contact
      dermatitis (ICD) was the main type of OSD. 36% of the bakers had an
      occupationally relevant Type I allergy, while Type I allergies were less frequent
      in confectioners (16%) and cooks (9%). Assuming a prevalence of 10% of AD in the
      general population the relative risk (RR) of developing OSD in bakers,
      confectioners and cooks with AD was 9.7, 10.5 and 5.2, respectively. There were
      only small differences in calculating sex-related RR of AD.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8549127
TI  - Prevalence of contact allergy to non-disperse azo dyes for natural fibers: a
      study in 1814 consecutive patients.
AB  - 5 non-disperse azo dyes, used for colouring natural fibers, were added to the
      standard patch test series, as 5% pet. preparations. 1814 consecutive patients
      attending the patch test clinic were patch tested, of whom 16 (0.88%) reacted to
      the newly added dyes: 8 to Direct Orange 34, 5 to Acid Yellow 61, 2 to Acid Red
      359 and 1 to Acid Red 118. On the basis of clinical history and results of patch
      tests with pieces of fabrics, contact sensitization to non-disperse azo dyes
      seemed to be related to the appearance of skin lesions at least in 8 subjects. We
      conclude that systematic exploration of the sensitizing potential of textile
      dyes, selected after careful investigation, can provide additional information on
      the frequency of occurrence of textile dye dermatitis, supporting individual
      investigation in sensitized subjects.

PMID- 8549128
TI  - Spontaneous repigmentation of vitiligo following generalized acute allergic
      contact dermatitis.

PMID- 8549129
TI  - Glycidyl methacrylate and ethoxyethyl acrylate: new allergens in emulsions used
      to impregnate paper and textile materials.

PMID- 8549130
TI  - Acute allergic contact dermatitis from Medi-Swabs, with negative patch tests to
      the individual ingredients, including isopropyl alcohol.

PMID- 8549131
TI  - Allergic contact dermatitis from dipentene in wax polish.

PMID- 8549132
TI  - Contact dermatitis from propylene glycol in Rifocine.

PMID- 8549133
TI  - Allergic contact dermatitis from nonoxynol-12 in a polish.

PMID- 8549134
TI  - Occupational dermatitis from ethylenediamine.

PMID- 8549135
TI  - Contact dermatitis from alpha-bromomethylparotolylsulfone.

PMID- 8549136
TI  - Allergic contact dermatitis from zinc pyrithione.

PMID- 8549137
TI  - Contact allergy to oleamidopropyl dimethylamine and related substances.

PMID- 8549138
TI  - Allergic contact dermatitis from Hedera helix L.

PMID- 8549139
TI  - Allergic contact dermatitis due to burdock (Arctium lappa).

PMID- 8549140
TI  - Contact dermatitis from heparin gel following sensitization by subcutaneous
      heparin administration.

PMID- 8549141
TI  - Contact sensitivity to 5 different ingredients of a topical medicament (Imacort
      cream).

PMID- 8549142
TI  - Occupational allergy to p-phenylenediamine in milk testers.

PMID- 8549143
TI  - Duration of response to UVA irradiation after application of a known
      photoallergen.

PMID- 8549144
TI  - Occupational allergic contact dermatitis due to formaldehyde and textile finish
      resins.

PMID- 8549146
TI  - Allergic contact dermatitis from retinoic acid.

PMID- 8549145
TI  - Allergic contact dermatitis due to timolol and levobunolol in eyedrops, with no
      cross-sensitivity to other ophthalmic beta-blockers.

PMID- 8549147
TI  - Contact allergy to imidazoles used as antimycotic agents.
AB  - The present article reviews the literature (up to 1994) on contact sensitivity to
      imidazoles and presents the results obtained from 15 patients observed at the
      Contact Allergy Unit in Leuven. The frequency as well as the cross-reaction
      patterns described are analyzed. Although allergic contact reactions may have
      been missed in the past (mainly because of problems with the correct choice of
      vehicle for patch testing), they seem to be relatively infrequent in view of
      their widespread use. The imidazole derivatives most frequently reported to be
      allergens are miconazole, econazole, tioconazole, and isoconazole. As far as
      cross-reactivity is concerned, statistically significant associations were found
      in the patient data between miconazole, econazole, and isoconazole; between
      sulconazole, miconazole, and econazole; and also between isoconazole and
      tioconazole. Patients sensitive to phenylethyl imidazoles (except ketoconazole)
      needing antimycotic therapy should be advised to use ketoconazole, clotrimazole,
      bifonazole, or, perhaps, the new flutrimazole. Clearly, non-imidazole antifungals
      can also be used.

PMID- 8549148
TI  - Double-blind placebo-controlled peroral challenges in patients with delayed-type
      allergy to balsam of Peru.
AB  - Patch tests (PTs) with spices, such as clove, cinnamon, Jamaica pepper and
      vanillin sugar, and with balsam of Peru were made on 29 patients 0.8-2.9 years
      after an allergy to balsam of Peru had been detected. Positive reactions to
      balsam of Peru were seen in 17 patients, and to clove, Jamaica pepper or cinnamon
      in 5. Double-blind placebo-controlled peroral challenges (DBPCPCs) with balsam of
      Peru and spices (active substances) were performed on 22 patients. A substantial
      increase (30-280%) in the number of palmar vesicles after the DBPCPC with the
      active substances, but not with placebo, was seen in 8 patients, an increase with
      both the active substances and placebo in 3, and with placebo but not the active
      substances in 1 patient. 4 of the 8 patients with positive DBPCPCs with the
      active substances were negative to balsam of Peru in the 2nd PT. No other
      objective symptoms were seen after the DBPCPCs. Balsam of Peru and the spices
      were retested 3 months after the DBPCPC. Both alleviation and aggravation of the
      PT reactions were seen. It is concluded that ingested flavoured foods might cause
      systemic contact reactions in some patients with allergy to balsam of Peru, but
      the benefits of a flavour-avoiding diet are questionable in all of them.

PMID- 8549149
TI  - Occupational allergic contact dermatitis from 2-hydroxyethyl methacrylate and
      ethylene glycol dimethacrylate in a modified acrylic structural adhesive.
AB  - Acrylates have a broad area of application in various products including glues,
      sealants and adhesives. Whereas anaerobic acrylic sealants are well-known
      sensitizers, acrylate glues that cure in air have only seldom been reported as
      allergens. Here a patient sensitized to such a glue, and developing hand
      dermatitis that spread to the lower arms, chest, neck and face, is presented. Her
      glue was analyzed by gas chromatography/mass spectrometry (GC/MS) and contained
      24.6% 2-hydroxyethyl methacrylate (2-HEMA) and 0.4% ethylene glycol
      dimethacrylate (EGDMA). These 2 acrylate compounds, as well as her glue, provoked
      an allergic patch test reaction. Also many other acrylate compounds, e.g.,
      tetrahydrofurfuryl methacrylate, gave an allergic reaction indicating cross
      allergy. The patient could not continue in her previous workplace because of
      severely relapsing skin symptoms.

PMID- 8549150
TI  - 2-methoxy-6-pentyl-1,4-dihydroxybenzene (miconidin) from Primula obconica: a
      possible allergen?
AB  - Miconidin (2-methoxy-6-pentyl-1,4-dihydroxybenzene) and the allergen primin (2
      methoxy-6-pentyl-1,4-benzoquinone) have been isolated from fresh unchopped plant
      material (leaves, stems and flowers together) of Primula obconica. Miconidin and
      primin were obtained in approximately equal amounts and their structures
      determined by NMR and GC-MS. Miconidin, which is biogenetically related to
      primin, has not previously been isolated from Primula species, and the
      possibility that miconidin is an allergen in P. obconica is discussed.

PMID- 8549152
TI  - Identification of arylamine N-acetyltransferase activity in the bovine lens.
AB  - Arylamine N-acetyltransferase (NAT) activity was identified and partially
      characterized in the bovine lens. According to size-exclusion HPLC, the molecular
      mass of the arylamine NAT is approximately 30-kDa. Based upon substrate
      specificity analysis, it is best described as an arylamine NAT which has some
      ability to N-acetylate arylalkylamines. This arylamine NAT acetylates para
      aminobenzoic acid thereby demonstrating a monomorphic pattern of N-acetylation.
      It demonstrates low sensitivity to methotrexate inhibition as indicated by the
      relatively high IC50 value (470 microM). NAT could be involved in lenticular
      detoxification of both endogenous amines and exogenous drugs.

PMID- 8549151
TI  - Occupational allergic contact dermatitis caused by epoxy diacrylate in
      ultraviolet-light-cured paint, and bisphenol A in dental composite resin.
AB  - Allergic contact dermatitis (ACD) caused by epoxy di(meth)acrylates or bisphenol
      A is rare. Here 2 such cases are reported. A dental assistant had allergic
      contact dermatitis (ACD) caused by bisphenol A contained in dental composite
      resin (DCR) products based on epoxy dimethacrylate. The contact allergy was
      verified by allergic patch test reactions to bisphenol A and 2 DCRs. The DCRs
      giving allergic reactions were analyzed, and 0.014-0.015% of bisphenol A was
      detected. Occupational ACD caused by bisphenol A in dental composite resins has
      not been described before. The other patient was a male process worker in a paint
      factory. He was sensitized by an epoxy diacrylate, 2,2-bis[4-(2-hydroxy-3
      acryloxypropoxy)phenyl]-propane (BIS-GA), and other acrylate compounds contained
      in raw materials of ultraviolet-light-curable paint. The epoxy diacrylate gave an
      allergic patch test reaction down to 0.016% in pet. He also had an allergic patch
      test reaction to several other acrylate compounds, 2-hydroxyethyl acrylate, 2
      hydroxypropyl acrylate, 1,4-butanediol diacrylate, 1,6-hexanediol diacrylate,
      diethyleneglycol diacrylate, triethylene glycol diacrylate, and tripropylene
      glycol diacrylate, indicating cross and/or concomitant sensitization.

PMID- 8549153
TI  - Expression of collagens I, III, IV and V mRNA in excimer wounded rat cornea:
      analysis by semi-quantitative PCR.
AB  - A semi-quantitative polymerase chain reaction (PCR) methodology was used to
      evaluate the kinetic changes occurring in collagens I, III, IV and V mRNA in rat
      cornea following excimer laser keratectomy. cDNA was synthesized from RNA
      extracted from rat cornea at various times following excimer laser photoablative
      keratectomy. Collagen cDNA sequences were subsequently amplified using specific
      sets of oligonucleotide primers. Competitive PCR amplification was carried out
      using an internal standard so that a semi-quantitative analysis of message for
      synthesis of collagen types I, III, IV and V could be performed and time course
      dynamics of message for these collagens studied. There was a biphasic increase in
      the levels of collagens III, IV and V mRNA following excimer laser keratectomy.
      Collagen I mRNA levels demonstrated a more sustained increase and were still
      elevated at 6 weeks following wounding. Collagens IV and V mRNA showed the
      largest increase with an approximate three fold increase over controls between 4
      days and 1 week. Our results demonstrate that upregulation of stromal collagens
      I, III, and V mRNA and basement membrane collagen IV mRNA occurs in rat cornea
      following excimer laser keratectomy.

PMID- 8549154
TI  - Suramin treatment suppresses induction of experimental autoimmune uveoretinitis
      (EAU) in rodents.
AB  - The experimental drug suramin has been shown to possess several immunosuppressive
      properties. In this study we investigated the effect of suramin on the
      development of experimental autoimmune uveoretinitis (EAU) in mice and in rats.
      EAU was induced either by active immunization with a uveitogenic protein or
      peptide, or by the adoptive transfer of a uveitogenic T cell line. The
      development of EAU was assessed by clinical evaluation as well as by
      histopathology. Immunological responses were measured by delayed type
      hypersensitivity (DTH), lymphocyte proliferation, and serum antibody levels to
      the immunizing antigen. Suramin treatment was most effective in suppressing EAU
      when started concurrently with immunization (afferent). Treatment was less
      effective in suppressing disease when first administered 7 days after
      immunization or when given to animals that received an adoptive transfer of
      uveitogenic T cells (efferent). The effect of suramin on DTH and lymphocyte
      proliferation roughly paralleled its effect on EAU. Aferent treatment of mice
      with suramin completely suppressed anti-IRBP antibody titers. Interestingly,
      animals receiving efferent treatment had unreduced IgM levels but little or no
      IgG, suggesting prevention of the IgM-to-IgG switch. Depressed in vitro
      lymphocyte proliferative responses in animals treated with suramin during the
      afferent stage suggested that the suppressive effect on disease was due at least
      in part to an inhibition of antigen priming. Our results suggest that suramin
      merits further investigation as a potential treatment for some types of uveitis.

PMID- 8549155
TI  - Influence of zinc on selected cellular functions of cultured human retinal
      pigment epithelium.
AB  - Zinc is a necessary micronutrient, usually abundant in human RPE. Our study was
      undertaken to determine the effects of short-term, zinc deficiency on human
      retinal pigment epithelium (RPE) using a culture model of fetal human RPE cells.
      Human fetal RPE cells were isolated and cultured in Coon's modified Ham's F-12
      medium. For zinc depletion studies, cells were cultured for 1 week in Chelex
      treated Dulbecco's modified Eagle's medium containing low (0.25 microM) or
      physiologic (11 microM) total zinc concentrations as determined by flame atomic
      absorption spectroscopy. Protein synthesis was determined by incorporation of 35S
      cysteine/methionine and labeled proteins analysed by polyacrylamide gel
      electrophoresis. Several cell parameters and enzymes were significantly reduced
      below control when cultured in low zinc: zinc content (40%), proliferation (63%),
      protein/well (50%), catalase activity (68%), alkaline phosphatase activity (61%),
      alpha-mannosidase activity (68%), and metallothionein (82%). No statistically
      significant decline was seen in acid phosphatase activity, superoxide dismutase
      activity, glutathione peroxidase activity and dexamethasone induction of
      metallothionein. Zinc repletion (100 microM, 1 h) increased catalase and alpha
      mannosidase activities from 32% and 33% of control to 75% and 73%, respectively.
      Cycloheximide did not inhibit this short-term zinc-induced repletion of catalase
      or alpha-mannosidase. Protein synthesis in low zinc medium was depressed, but not
      significantly, as shown by incorporation of radiolabeled 35S-cysteine/methionine
      into newly synthesized proteins. The effects of zinc deficiency in cultured human
      RPE are selective. Adequate intracellular zinc was required for maximal activity
      of some enzymes. The dependence of catalase activity on zinc was not predicted
      and may help explain the observed decline in catalase activity seen with age in
      RPE. Our model of zinc deficiency should prove useful in elucidating the complex
      effects of zinc deficiency and repletion in human RPE.

PMID- 8549156
TI  - IGF-I and EGF receptors in the pigmented rabbit bulbar conjunctiva.
AB  - The purpose of this study was to investigate whether receptors for insulin-like
      growth factors I and II (IGF-I and IGF-II), insulin, epidermal growth factor
      (EGF), and transforming growth factor alpha (TGF alpha) are present on the apical
      surface of the pigmented rabbit bulbar conjunctiva. Binding of 125I-labelled
      ligands to the apical surface of the pigmented rabbit bulbar conjunctiva was
      conducted at 4 degrees C in the absence and presence of excess unlabeled ligands.
      There was no evidence for the existence of IGF-II, insulin or TGF alpha receptors
      in the isolated pigmented bulbar conjunctiva. Only IGF-I and EGF receptors
      appeared to be present. The apparent dissociation constant (Kd) of IGF-I
      receptors was 206 +/- 13 pM and that for EGF was 51 +/- 5 pM. The number of
      receptors per 95 mm2 of bulbar conjunctiva was (6.0 +/- 0.2)X10(9) for IGF-I and
      (2.4 +/- 0.1)X10(9) for EGF. There was no crossover binding of either IGF-I or
      EGF to one another's receptors. The IC50 value for competitive displacement of
      bound 125I-IGF-I was: 44 +/- 2 nM by IGF-I, 156 +/- 13 nM by IGF-II and 812 +/-
      78 nM by insulin. The IC50 value for displacement of bound 125I-EGF was 0.37 +/-
      0.03 nM by EGF and 0.42 +/- 0.04 nM by TGF alpha. In conclusion, only IGF-I and
      EGF receptors appear to be present on the apical surface of the pigmented rabbit
      bulbar conjunctiva. The IGF-I receptor is also capable of binding IGF-II and
      insulin, whereas the EGF receptor is also capable of binding TGF alpha.

PMID- 8549157
TI  - Contactin/F11 and tenascin-C co-expression in the chick retina correlates with
      formation of the synaptic plexiform layers.
AB  - The neural immunoglobulin-like cell adhesion molecule contactin/F11 and the
      extracellular matrix glycoprotein tenascin-C are prominent molecules in the
      developing nervous system which interact in in vitro assays (Zisch et al., J.
      Cell Biol. 119, 203-213). To determine their potential role in neural
      development, the distribution of tenascin-C and contactin/F11 was examined in the
      developing chick retina. The onset of both tenascin-C and contactin/F11
      expression coincides with the appearance of ganglion cell dendrides and neurites
      from bipolar and amacrine cells in the inner layer (IPL) at E8, and the extension
      of bipolar and horizontal cell processes in the outer plexiform layer (OPL) at
      E9. Contactin/F11 expression is co-ordinately upregulated with the TN190 and
      TN200 tenascin-C isoforms between embryonic day 8 (E8) and E17, while little, if
      any, of the TN220 isoform, which does not bind contactin/F11, is detected. In
      situ hybridization reveals that tenascin-C and contactin/F11 mRNAs are
      synthesized by different neuronal types. Tenascin-C mRNA probes hybridize to
      amacrine and displaced amacrine neurons, and horizontal neurons. In cultured
      retinal cells, tenascin-C is also present on process-bearing neurofilament
      positive cells. Contactin/F11 mRNA is detected in bipolar cells or their
      precursors from E8-9, and later in horizontal and ganglion neurons. The highest
      levels and greatest overlap in the synaptic IPL and OPL are reached at E17, when
      the stratification of the retina is nearly complete. These results are consistent
      with a putative role for contactin/F11-tenascin-C interactions in the
      establishment of synaptic layers in the retina.

PMID- 8549158
TI  - Active sodium and chloride transport across the isolated rabbit conjunctiva.
AB  - The bulbar-palpebral conjunctiva from albino rabbits was dissected as a cylinder
      and cut longitudinally to convert it to a flat epithelium that was mounted as a
      partition between Using-type chambers, exposing 0.38 cm2 of cross-sectional area.
      The tissue was bathed with a modified Tyrode's solution at 37 degrees C, pH 7.5.
      The tear-facing side (apical) was 14.6 +/- 1.5 mV negative relative to the
      basolateral side. Transepithelial resistance was 1.23 +/- 0.01 K omega.cm2 and
      the short-circuit current (Isc) was 14.4 +/- 1.3, microA/cm2. Sixty percent of
      the Isc could be accounted for by a Na(+)-dependent, bumetanide-inhibitable Cl-
      transport directed towards the apical side. The remainder of the Isc reflected a
      Na+ absorptive process at the apical surface that was amiloride resistant.
      Evidence was obtained that a likely contributor to this activity is an
      electrogenic Na(+)-glucose co-carrier. The Cl-dependent Isc was stimulated by
      forskolin and epinephrine. Permeabilization of the apical membrane with
      amphotericin B evinced a current carried by a basolateral Na+:K+ pump. An effect
      by heptanol suggested that part of the Isc traverse the epithelium via gap
      junctions. Our results imply that transport processes at the conjunctiva could
      influence the composition of the tear film.

PMID- 8549159
TI  - Interspecies comparisons of lens phospholipids.
AB  - The purpose of this study was to compare and contrast quantitative crystalline
      lens phospholipid profiles among human, pig, rabbit, rat mouse, dog, lamb, guinea
      pig, beef, calf, chinook salmon, and golden roach. Lenses were extracted using
      chloroform-methanol. The extracts were prepared for phospholipid 31P NMR
      quantitative analysis using an NMR analytical reagent specifically designed for
      this purpose. Lens phospholipid profiles vary among vertebrate species. Thirteen
      different phospholipids [phosphatidylglycerol, lysophosphatidylethanolamine,
      phosphatidic acid, diphosphatidylglycerol, the ethanolamine plasmalogen (EPLAS),
      phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM),
      lysophosphatidylcholine, phosphatidylcholine (PC), including four uncharacterized
      (unknown) phospholipids at 1.31 ppm (human), 1.20 ppm (human, rabbit, dog, lamb,
      beef, calf), 0.13 ppm (all except rat), and -0.17 ppm (rat, beef) were detected.
      EPLAS, PE, PS, SM, and PC are the major lens phospholipids in all species except
      the human, where the major phospholipid is the unknown at 0.13 ppm. The lens
      content of this major unknown in mole percentage of the total detected
      phospholipid profile is: human 43.7; pig 6.7; rabbit, 6.1; rat (not detected);
      mouse, 3.2; dog, 5.0; guinea pig, 2.0; lamb, 7.0; beef, 7.7; calf, 5.6; chinook
      salmon, 6.7; and golden roach, 1.6. Large qualitative and quantitative
      differences were observed among lens species, indicating the necessity for
      prudent selection of appropriate animal models. The most striking finding is that
      no other species except the human species exhibits such a profound amount of the
      unknown phospholipid at 0.13 ppm. In the human lens, this phospholipid is the
      major phospholipid.

PMID- 8549160
TI  - Vitamin C reduces cytochalasin D cataractogenesis.
AB  - The effect of cytochalasin D (CD), an actin monomer-stabilizer, has been studied
      on cataract development in rat lenses. Cataractogenesis was induced by incubating
      the rat lenses in medium 199 (M199) containing 10(-5) M CD; by the end of 24 h,
      lenses first developed a visible opacity. The increased lactate dehydrogenase
      (LDH) activity in the culture medium, leakage of lens cytosolic proteins into the
      culture medium and observable development of opacity through a dissection
      microscope were correlated with cell damage associated with cataract formation.
      Non-denaturing polyacrylamide gel electrophoresis was used to separate three lens
      LDH isoenzymes. The effect of 1 mM vitamin C (VC) in reducing LDH leakage was
      also examined. The protective effect of VC on CD-initiated cataractous lenses is
      significant. This suggest that a portion of the opacity and lens damage may
      involve oxidative damage to the membrane-cytoskeleton complex which is started by
      CD, but partially prevented by VC

PMID- 8549161
TI  - Further studies on the dynamic changes of glutathione and protein-thiol mixed
      disulfides in H2O2 induced cataract in rat lenses: distributions and effect of
      aging.
AB  - To further investigate the role of protein-thiol mixed disulfides in
      cataractogenesis, an in vitro H2O2 cataract model was used with rat lenses to
      study the effect of aging, and the dynamic changes in the cortex, nucleus and the
      lens protein fractions. A group of lenses was exposed to H2O2-containing media
      (0.6 mM) for 1 to 3 days so that cortical cataract was induced gradually. Another
      group of lenses was first subjected to H2O2 exposure for one day and then
      recovered in the oxidant-free media for one or two days. These lenses were
      examined for the distribution of free glutathione and protein-thiol mixed
      disulfides (protein-glutathione and protein-cysteine) in the cortical and nuclear
      regions as well as in the water soluble and water insoluble fractions. Similar to
      the results reported earlier, the glutathione depletion in the whole lens
      occurred immediately and extensively during the 3-day H2O2 exposure. This loss
      was evenly distributed in the cortical and nuclear fractions. The level of
      protein-glutathione increased rapidly and continued throughout the 3 days. Most
      of the accumulation was found in the cortex and in both lens protein fractions.
      The protein-cysteine modification responded more slowly and less to oxidative
      stress. The delayed formation occurred mainly in the nucleus and in both lens
      protein fractions. In the recovery group, glutathione depletion was less drastic
      in the cortical and nuclear regions, but the elevated protein-glutathione in both
      regions and both protein fractions spontaneously decreased to its respective
      basal level within 1 day. Protein-cysteine on the other hand remained quite high,
      and in some cases it continued to rise in the absence of oxidation. Aging showed
      little effect on the response of rat lenses to oxidative stress. Similar patterns
      in glutathione and protein-thiol mixed disulfides occurred in both age groups (1,
      23 months) and in both chronic oxidative stress and recovery conditions.

PMID- 8549162
TI  - Localization of a corneal basement membrane glycoconjugate in bovine eye.
AB  - Lectin histochemistry was used to analyze the ocular surface basement membrane in
      order to identify novel, tissue-specific glycoconjugates. Soybean agglutinin
      (SBA), a lectin marker for N-acetylgalactosamine residues, recognized a 130 kDa
      glycoconjugate in corneal but not conjunctival basement membrane. Following
      corneal epithelial cell wounding in vitro, the glycoconjugate was not expressed
      at the epithelial cell-stromal interface until 72-96 h in culture, much later
      than the expression of other basement membrane molecules. In epithelial cells
      maintained on various extracellular matrix substrates (laminin, collagen type IV,
      or a mixture of laminin, collagen type IV and heparan sulfate proteoglycan), the
      glycoconjugate localization patterns changed with time in culture from a diffuse
      cellular or perinuclear ring to an extensive extracellular filament network. The
      presence of SBA in the culture medium did not affect migration or adhesion in
      either the wound healing model or in culture cells. However, the presence of SBA
      did delay the deposition of laminin at the zone of basement membrane reformation
      in the wound healing model. The 130 kDa glycoconjugate is a candidate for
      molecules which impart a tissue-specificity to the corneal basement membrane, and
      which may be involved in cell-matrix interaction.

PMID- 8549163
TI  - Characterization of P. aeruginosa pili binding human corneal epithelial proteins.
AB  - Soluble human corneal epithelial proteins (hcep) to which P. aeruginosa pili bind
      were identified and characterized using gel electrophoresis and Western blotting
      techniques. Pilus binding proteins were identified using nitrocellulose membrane
      blots of one dimensional polyacrylamide gels (1-D-SDS-PAGE) of solubilized hcep
      and a pilus overlay assay. Five major proteins of approximate molecular weights <
      21, 38, 45, 66, 97 (a doublet) kilodaltons (kDa) and two additional proteins of >
      97 kDa bound pili using an overlay assay and immunoblotting with the monoclonal
      antibody (MAb) XLR-3, specific for pili. Several of these pili binding proteins
      were confirmed as single proteins using a similar pilus overlay assay and blotted
      proteins from two-dimensional polyacrylamide gels (2-D-SDS-PAGE) of hcep. A solid
      phase binding assay confirmed that pili binding to hcep was specific, competitive
      and saturable. The importance of the carbohydrate portions of corneal pili
      binding proteins was assessed by preincubation of 1-D gel blots of hcep or dot
      blots of selected eluted pilus binding proteins ( < 21, 38, 45, 66 and 97 kDa)
      with periodic acid. Mild periodate oxidation of blots before pilus overlay assay
      completely abolished pili binding. The role of glycosylation of proteins also was
      assessed using 1-D blots of hcep or dot blots of eluted pilus binding proteins.
      These blots were preincubated with different lectins before incubation with pili
      in the pilus overlay assay. Of several lectins examined, only sConA, which
      recognizes terminal mannose residues, prevented pili binding in the pilus overlay
      assay. These studies provide evidence that several human corneal epithelial
      glycosylated proteins provide receptor sites for bacterial pili binding, and that
      the binding of pili to these proteins is specific, competitive and saturable.
      They also show that the carbohydrate mannose functions as an integral component
      of hcep pili binding receptors.

PMID- 8549164
TI  - The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal analysis and
      chromosome mapping.

PMID- 8549165
TI  - Echocardiographic and other noninvasive measurements of cardiac hemodynamics and
      ventricular function.

PMID- 8549166
TI  - VATS anatomic lung resections. The Hong Kong experience.

PMID- 8549167
TI  - Temporal trends in the prevalence of malignancy in resected solitary pulmonary
      lesions.
AB  - STUDY OBJECTIVE: To determine whether there has been an increase in the
      prevalence of malignancy among resected, indeterminate solitary pulmonary lesions
      (SPL) over the past 14 years. DESIGN: A retrospective review of all thoracotomies
      for indeterminate SPLs from 1981 through 1994. SETTING: A university-affiliated
      VA Medical Center. PATIENTS: Three-hundred seventy resected indeterminate SPLs
      (all < or = 6 cm) in 360 patients. MEASUREMENTS AND RESULTS: Virtually all
      patients were men with an average age of 63 +/- 9 years. The average lesion size
      was 2.5 +/- 1.4 cm; 71% were 3 cm or less. Overall, 79% of resected lesions were
      malignant; 94% of these were bronchogenic carcinomas. Granulomas accounted for
      more than 50% of benign lesions. The proportion of malignant diagnoses increased
      from 55 to 60% in 1981 to 1983 to 90 to 100% in 1990 to 1994 (p < 0.005). The
      increasing proportion of malignancy over time was independent of age at time of
      operation and lesion size. There was no significant difference in survival among
      patients with a malignant lesion resected in 1981 to 1983 compared with 1990 to
      1994. CONCLUSION: We conclude that there has been a striking increase in the
      prevalence of malignancy among resected indeterminate SPLs over the past 14 years
      in our institution. We suspect that this trend reflects improvements in our
      ability to diagnose benign SPLs preoperatively, primarily through the use of CT.
      Our results should prompt other institutions to review their recent experience
      with the diagnosis of indeterminate SPLs to provide more timely information to
      physicians and their patients who are contemplating resection of SPLs.

PMID- 8549169
TI  - Aspects of histopathologic subtype as a prognostic factor in 85 pleural
      mesotheliomas.
AB  - BACKGROUND: The prognosis of patients with pleural mesothelioma is more dependent
      on "pretreatment factors" than on the effect of therapeutic interventions.
      Histopathologic subtype is one of several important prognostic factors in pleural
      mesothelioma, and several studies indicate that the epithelial subtype of pleural
      mesotheliomas has a more favorable prognosis than the sarcomatoid. In this study,
      we retrospectively evaluated qualitative and quantitative aspects of the tissue
      specimens used for histopathologic diagnosis in 85 patients with pleural
      mesothelioma. MATERIALS AND METHODS: The prognostic roles of two different
      histopathologic classification systems were evaluated in 85 consecutive cases of
      pleural mesotheliomas. Efficiency of different diagnostic procedures, influence
      of the size of the biopsy specimens on the histopathologic diagnosis, and
      immunohistochemical profiles for histopathologic subtypes of mesotheliomas were
      also evaluated. RESULTS: Patients with pure epithelial mesotheliomas (n = 35),
      and especially those with the tubulopapillary subtype (n = 18) of epithelial
      mesotheliomas, survived significantly longer than those with a sarcomatoid
      component (n = 50). With larger biopsy specimens (surgical biopsy, autopsy), more
      tumors were classified as biphasic (36/78 vs 9/44, p < 0.005). The sarcomatoid
      mesotheliomas comprised about 20% of the tumors regardless of type of biopsy.
      Staining intensity for cytokeratin CAM 5.2 was equal in all types of
      mesotheliomas, while intensity with cytokeratin AE1/AE3 decreased from the
      epithelial to the sarcomatoid mesotheliomas. Staining with vimentin was most
      intense among the sarcomatoid mesotheliomas, while with epithelial membrane
      antigen it was most intense among the epithelial mesotheliomas. CONCLUSIONS: The
      quality of the biopsy specimens has considerable impact on the possibility to
      arrive at a correct histopathologic diagnosis. Based on our results, we suggest
      tubulopapillary mesotheliomas be regarded as "low-grade mesotheliomas" and other
      types, including the epithelioid type of epithelial mesotheliomas, as "high-grade
      mesotheliomas." This should be taken into account when designing clinical trials.

PMID- 8549168
TI  - Cytokeratin tumor marker levels in bronchial washing in the diagnosis of lung
      cancer.
AB  - STUDY OBJECTIVE: The monitoring of serum concentrations of Cyfra 21-1, tumor
      polypeptide antigen (TPA), and tissue polypeptide specific antigen (TPS) has been
      demonstrated to be useful in the clinical treatment of patients with lung cancer.
      This study was planned to evaluate the clinical usefulness of the assay of these
      tumor markers on bronchial washing (BW) fluid and to compare it with serum assay
      in patients with neoplastic and nonneoplastic disease. STUDY DESIGN: Serum and BW
      fluid levels of Cyfra 21-1, TPA, and TPS were measured in 40 subjects (10 control
      subjects, 11 with chronic bronchitis, 10 with squamous cell lung cancer, and 9
      with nonsquamous cell lung cancer) undergoing diagnostic bronchoscopy. BW was
      performed using 25 mL of pyrogen-free saline solution instilled through the
      working channel of the bronchoscope, and successively aspirated. The quantity of
      the fluid recovered was measured and used for the assay of albumin, Cyfra 21-1,
      TPA, and TPS. RESULTS: Mean BW concentrations of Cyfra 21-1, TPA, and TPS
      concentrations were significantly higher than serum concentrations (p < 0.01).
      Serum Cyfra 21-1, TPA, and TPS concentrations were significantly lower in
      controls and in those with chronic bronchitis than in patients with epidermoid
      and nonepidermoid carcinoma (p < 0.01). No difference in serum concentrations of
      the three markers was observed between controls and patients with chronic
      bronchitis. On the contrary, BW Cyfra 21-1 and TPA concentrations were
      significantly higher in those with chronic bronchitis and in cancer patients than
      in controls (p < 0.01), whereas they did not differ between patients with chronic
      bronchitis and cancer patients. No significant difference in BW TPS concentration
      was observed among the four groups. Sensitivity and specificity of the BW markers
      in diagnosing lung cancer were as follows: 68.4% and 61.9% for Cyfra 21-1; 68.4%
      and 66.6% for TPA; and 57.9% and 66.6% for TPS. CONCLUSIONS: BW fluid
      concentrations of Cyfra 21-1 and TPA are increased in patients with chronic
      bronchitis and in patients with lung cancer. Being unable to distinguish
      malignant from nonmalignant inflammatory conditions, the measurement of airway
      concentrations of such markers has a too-low specificity to be considered useful
      in diagnosing malignant abnormalities of the lung.

PMID- 8549170
TI  - End-of-life discussions with patients. Timing and truth-telling.

PMID- 8549171
TI  - Woodsmoke exposure and risk for obstructive airways disease among women.
AB  - OBJECTIVE: To investigate if exposure to firewood smoke and other indoor
      pollutants is a potential risk factor for obstructive airways disease (OAD) among
      women in Bogota in whom cigarette smoking and other known risk factors may not be
      the most frequent. DESIGN AND SETTING: We conducted a hospital-based case-control
      study to identify risk factors for OAD among women in Bogota. An interview was
      conducted using a modified questionnaire recommended by the American Thoracic
      Society for epidemiologic studies. PATIENTS: We compared 104 OAD cases with 104
      controls matched by hospital and frequency matched by age. ANALYSIS: The odds
      ratio (OR) was used as the basic statistic to evaluate risk. Multivariate
      analysis (MA) was conducted by the Mantel-Haenszel procedure and by logistic
      regression. MAIN RESULTS: Univariate analysis showed that tobacco use (OR = 2.22;
      p < 0.01), wood use for cooking (OR = 3.43; p < 0.001), passive smoking (OR =
      2.05; p = 0.01), and gasoline use for cooking (OR = 0.52; p = 0.02) were
      associated with OAD. Trends for years of tobacco use and years of wood cooking
      were present (p < 0.05). After MA, variables remained significant except gasoline
      use. CONCLUSIONS: This study showed that among elderly women of low socioeconomic
      status in Bogota, woodsmoke exposure is associated with the development of OAD
      and may help explain around 50% of all OAD cases. The role of passive smoking
      remains to be clarified. This work may set the basis for interventional studies
      in similar settings.

PMID- 8549172
TI  - Longitudinal pattern of reported respiratory symptoms and accelerated ventilatory
      loss in asbestos-exposed workers.
AB  - Studies investigating the relation between respiratory symptoms and change in
      ventilatory function have been limited by use of reported symptoms at a single
      point in time. To assess the relation between the longitudinal pattern of
      reported cough, phlegm, wheeze, and dyspnea and ventilatory loss, we
      prospectively investigated changes in FVC and FEV1 associated with development,
      resolution, or persistence of these symptoms over a 3- to 5-year period in 446
      asbestos-exposed workers. Longitudinally reported symptoms changed frequently,
      with 52 to 61% of subjects reporting a specific symptom noting resolution or
      development of that symptom during follow-up. Initially reported symptoms were
      not predictive of accelerated loss of FVC or FEV1. In contrast, development of
      any new respiratory symptom, and to a lesser extent persistence of symptoms
      during follow-up, were associated with significantly greater ventilatory losses
      compared with asymptomatic individuals, ranging from 28 mL/yr in FEV1 for newly
      developed dyspnea, to 67 mL/yr in FVC for developed wheeze (p < 0.01). We
      conclude that development or persistence of respiratory symptoms over time,
      rather than the presence of symptoms per se, is predictive of future ventilatory
      loss. Recognition of interval changes in symptom reporting during surveillance of
      asbestos-exposed workers may effectively identify groups at risk for progressive
      ventilatory impairment.

PMID- 8549173
TI  - The half-moon sign. A useful roentgen sign of saccular aneurysm of the aortic
      arch.
AB  - OBJECTIVE: The half-moon sign is defined as a shadow seen on the lateral chest
      radiograph consisting of a smooth, partially demarcated opacity with the rounded
      portion of the half moon projecting over the aortic lumen at the level of the
      aortic arch, but the rest of the opacity merging with the aorta. In this study,
      we intended to evaluate the clinical usefulness of half-moon sign in aiding a
      diagnosis of saccular aneurysm of the aortic arch. METHODS: This series consisted
      of 57 patients with aortic arch aneurysm and 46 patients with a variety of
      nonvascular intrathoracic masses that presented as soft-tissue masses adjacent to
      the aortic arch on the frontal chest radiographs. The half-moon sign was
      evaluated independently by two senior chest radiologists who had no knowledge of
      the final causes. RESULTS: The half-moon sign was shown on the lateral chest
      radiographs in 5 of 10 patients with saccular aortic arch aneurysm but absent in
      47 patients with fusiform aortic arch aneurysm. Furthermore, this roentgen sign
      was not seen on the lateral chest radiographs in 46 patients with nonvascular
      intrathoracic masses. In this selected population, the sensitivity and
      specificity of the half-moon sign in aiding a diagnosis of saccular aneurysm of
      the aortic arch were 50% and 100%, respectively. CONCLUSION: The half-moon sign
      shown on the lateral chest radiograph is highly suggestive of the saccular aortic
      arch aneurysm.

PMID- 8549175
TI  - Quantitative CT predicts the severity of physiologic dysfunction in patients with
      lymphangioleiomyomatosis.
AB  - PURPOSE: To assess quantitative high-resolution CT (quantitative CT) as a
      diagnostic and prognostic tool in pulmonary lymphangioleiomyomatosis. METHODS:
      Spirometry, lung volumes, diffusing capacity, exercise physiology, and expiratory
      high-resolution CT (HRCT) examinations were performed on a cohort of ten patients
      with the diagnosis of lymphangioleiomyomatosis (LAM) referred to a tertiary care
      center. HRCT examinations were also done on ten normal control subjects. A
      thresholding technique was used to quantitatively assess the amount of abnormal
      cystic parenchyma present on each of the two images obtained for each subject
      with LAM and for each normal control subject. This numeric index of cystic
      parenchyma, the quantitative CT index, was then examined (1) as a diagnostic
      measure to distinguish the subjects with LAM from the normal control subjects and
      (2) as a prognostic measure to assess disease severity in the subjects with LAM.
      Linear regression of the quantitative CT index against physiologic indexes of
      pulmonary function and exercise performance was analyzed to determine the
      relationship between this radiologic assessment of disease severity and
      functional impairment. RESULTS: The quantitative CT index was significantly
      greater for the LAM patients, 37.2 +/- 6.9 (SEM), compared with the control
      group, 0.8 +/- 0.2 (p = 0.0001). Linear regression analysis demonstrated
      significant linear correlation between the quantitative CT index and measures of
      airflow (FEV1, r = -0.90, p = 0.0005), air trapping (residual volume, r = 0.70, p
      = 0.02), diffusing capacity (diffusing capacity for carbon monoxide, r = -0.76, p
      = 0.01), gas exchange (alveolar to arterial oxygen gradient) at rest, r = 0.69, p
      = 0.007, and at maximum exercise, r = 0.79, p = 0.007) and exercise performance
      (maximum workload, r = -0.84, p = 0.002), and oxygen utilization (oxygen
      utilization at maximum exercise, r = -0.76, p = 0.01). CONCLUSION: Quantitative
      CT techniques can distinguish subjects with LAM from normal controls. Further,
      the quantitative CT index correlates well with physiologic measurements of
      airflow, lung volumes, diffusing capacity, and exercise performance and, thus,
      may provide a useful measure of disease severity.

PMID- 8549174
TI  - Video-assisted thoracoscopic anatomic lung resections. The initial Hong Kong
      experience.
AB  - We report our combined experience on video-assisted thoracoscopic (VAT) anatomic
      lung resections from two major hospitals in Hong Kong over a 17-month period.
      From August 1993 to December 1994, 82 cases of major lung resections were
      attempted using the VATS approach, of which 60 were successfully completed (55
      lobectomies, 2 bilobectomies, 2 pneumonectomies, and 1 segmentectomy). Of these
      60 cases, there were 43 men and 17 women with a mean age of 66 years (range, 37
      to 85 years). The final pathologies were 52 primary lung cancers (37
      adenocarcinoma, 11 squamous cell carcinoma, 2 bronchoalveolar carcinoma, 1
      adenosquamous carcinoma, and 1 undifferentiated carcinoma); 1 pulmonary
      metastasis (from nasopharyngeal carcinoma); and 7 benign lesions (3 tuberculosis,
      1 bronchiectasis, 1 sclerosing hemangioma, 2 organizing pneumonia). There was one
      postoperative death (mortality rate, 1.8%). Complications include persistent air
      leak over 10 days (four), wound infection (two), supraventricular tachycardia
      (three), and recurrence of tumor over the utility thoracotomy scar (one). All the
      patients were followed up from 8 weeks to 19 months (mean, 10 months). The mean
      duration of chest drainage was 5.4 days (range, 2 to 25 days). The mean hospital
      stay was 7.2 days (range, 4 to 35 days). The average postoperative parenteral
      narcotic (meperidine hydrochloride [Pethidine]) requirement by patient-controlled
      analgesia was 275 mg (range, 75 to 800 mg). This compared favorably with an age-
      and sex-matched historic group of patients who underwent posterolateral
      thoracotomy and had a hospital stay of 10.4 days (statistically non-significant)
      and narcotic requirement of 950 mg (statistically significant by paired t test).
      We conclude that VAT anatomic lung resection is technically feasible. However,
      there are some specific complications associated with major lung resection
      through minimal access. Refinement of our present technique and attention to
      details are important to improve our results.

PMID- 8549176
TI  - Sleep apnea after 1 year domiciliary nasal-continuous positive airway pressure
      and attempted weight reduction. Potential for weaning from continuous positive
      airway pressure.
AB  - STUDY OBJECTIVE: To assess the effect of 1 year of therapy for sleep apnea
      syndrome (SAS) combining domiciliary nasal-continuous positive airway pressure (N
      CPAP) and attempted weight loss on the severity of disease and to evaluate the
      potential for weaning from continuous positive airway pressure (CPAP). METHODS
      AND PROCEDURES: Ninety-five patients having a baseline apnea hypopnea index (AHI)
      greater than 10/h were prescribed N-CPAP at home. Weight loss was attempted by
      dietary counseling and by single ring vertical gastroplasty in those patients
      with a body mass index (BMI) greater than 40 kg/m2. Subjects were asked to return
      after 1 year for a full-night polysomnography (PSG) without CPAP and the results
      were compared with baseline PSG. RESULTS: Thirty-nine patients compliant to CPAP
      were evaluated. Weight had decreased from 108.3 +/- 29.0 to 99.7 +/- 17.7 kg as a
      result of dietary counseling (n = 36) or gastroplasty (n = 3). A significant
      improvement was found in AHI (66.5 +/- 28.7-->50.3 +/- 38.4/h; p < 0.05), maximal
      duration of apnea or hypopnea (66 +/- 22-->47 +/- 18 s; p < 0.001), minimal
      oxyhemoglobin saturation (62 +/- 16-->78 +/- 7%; p < 0.001), and stage shift
      index (SSI) (76 +/- 29-->62 +/- 28/h; p < 0.05). The drop in AHI correlated with
      the reduction in BMI (r = 0.47; p < 0.01) and with the decrease in SSI (r = 0.50;
      p < 0.001). Weaning from CPAP was proposed to six patients and succeeded in four
      (three with 29, 93, and 94 kg weight loss, respectively, and one subject with a
      normal unchanged weight). CONCLUSION: In 39 patients with SAS, 1-year domiciliary
      N-CPAP combined with weight loss resulted in a significant improvement in
      breathing during sleep and in sleep fragmentation, as judged from PSG without
      CPAP. Four subjects were successfully weaned, three of whom had in parallel a
      substantial decrease in weight.

PMID- 8549177
TI  - Total respiratory system, lung, and chest wall mechanics in sedated-paralyzed
      postoperative morbidly obese patients.
AB  - OBJECTIVE: To study the relative contribution of the lung and the chest wall on
      the total respiratory system mechanics, gas exchange, and work of breathing in
      sedated-paralyzed normal subjects and morbidly obese patients, in the
      postoperative period. SETTING: Policlinico Hospital, University of Milan, Italy.
      METHODS: In ten normal subjects (normal) and ten morbidly obese patients (obese),
      we partitioned the total respiratory mechanics (rs) into its lung (L) and chest
      wall (w) components using the esophageal balloon technique together with airway
      occlusion technique, during constant flow inflation. We measured, after abdominal
      surgery, static respiratory system compliance (Cst,rs), lung compliance (Cst,L),
      chest wall compliance (Cst,w), total lung (Rmax,L) and chest wall (Rmax,w)
      resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance
      (DR,L). DR,L represents the component due to viscoelastic phenomena of the lung
      tissue and time constant inequalities (pendelluft). Functional residual capacity
      (FRC) was measured by helium dilution technique. RESULTS: We found that morbidly
      obese patients compared with normal subjects are characterized by the following:
      (1) reduced Cst,rs (p < 0.01), due to lower Cst,L (55.3 +/- 15.3 mL x cm H2O-1 vs
      106.6 +/- 31.7 mL x cm H2O-1; p < 0.01) and Cst,w (112.4 +/- 47.4 mL x cm H2O-1
      vs 190.7 +/- 45.1 mL x cm H2O-1; p < 0.01); (2) increased Rmin,L (4.7 +/- 3.1 mL
      x cm H2O x L-1 x s; vs 1.0 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01) and DR,L (4.9
      +/- 2.6 mL x cm H2O x L-1 x s; vs 1.5 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01);
      (3) reduced FRC (0.665 +/- 0.191 L vs 1.691 +/- 0.325 L; p < 0.01); (4) increased
      work performed to inflate both the lung (0.91 +/- 0.25 J/L vs 0.34 +/- 0.08 J/L;
      p < 0.01) and the chest wall (0.39 +/- 0.13 J/L vs 0.18 +/- 0.04 J/L; p < 0.01);
      and (5) a reduced pulmonary oxygenation index (PaO2/PAO2 ratio). CONCLUSION:
      Sedated-paralyzed morbidly obese patients, compared with normal subjects, are
      characterized by marked derangements in lung and chest wall mechanics and reduced
      lung volume after abdominal surgery. These alterations may account for impaired
      arterial oxygenation in the postoperative period.

PMID- 8549178
TI  - The accuracy of a handheld portable spirometer.
AB  - BACKGROUND: Objective measurement of lung function is considered essential in the
      management of patients with asthma and COPD. Many primary care practitioners lack
      the means necessary to obtain these measurements conveniently. To meet this need,
      electronic spirometers, offering portability, ease of operation, and timesaving
      readout options have been introduced. We compared the accuracy of a typical
      pneumotachograph-based device with a conventional volume displacement spirometer.
      METHODS: We compared indexes of pulmonary function (FVC, FEV1, mean forced
      expiratory flow during the middle half of FVC, [FEF25-75%], and peak expiratory
      flow rate [PEFR]) measured by the handheld device with those measured by a
      conventional spirometer in 75 white subjects (33 men, 42 women) with a median age
      of 43 years (22 to 77 years) who were either healthy or were referred to the
      pulmonary function laboratory of a large tertiary care teaching hospital. The
      order of the instrument tested first was randomized and the patients were blinded
      to which instrument was being studied. RESULTS: There was a linear relationship
      between instruments for all indexes measured (r = 0.97, 0.98, 0.94, 0.94 for FVC,
      FEV1, FEF25-75%, and PEFR, respectively, for all p < 0.001). The random error
      (precision) was within 5% only for FEV1. The mean of the differences between the
      values obtained using both instruments (the bias) +/- limits of agreement (+/- 2
      SD) were 0.06 +/- 0.56 L for FVC (p = NS), 0.2 +/- 0.44 L for FEV1 (p < 0.05),
      0.61 +/- 1.26 L/s for FEF25-75% (p < 0.05), and 0.44 +/- 1.9 L/s for PEFR (p <
      0.05). CONCLUSION: Our data suggest that measurements obtained using the
      pneumotachograph device are closely related to those obtained by volume
      displacement spirometry and that the handheld device may be useful in clinical
      practice. However, because the limits of agreement are wide and the difference
      between the two instrument measurements are significant for FEV1, FEF25-75%, and
      PEFR, the bias between them is not consistent nor is it insignificant. Therefore,
      the measurements made with the two types of machine cannot be used
      interchangeably.

PMID- 8549179
TI  - The etiology of pleural effusions in an area with high incidence of tuberculosis.
AB  - To investigate the etiology of pleural effusions in our region, we undertook a
      prospective study of patients with this condition in our centers. During a 5-year
      period, we studied 642 pleural effusion patients aged 57.1 +/- 21.1 years, of
      whom 401 were men aged 56.5 +/- 21 years and 241 were women aged 57.8 +/- 21.4
      years; the male/female ratio was 1.6:1. The most frequent cause of pleural
      effusion was tuberculosis (25%), followed by neoplasia (22.9%) and congestive
      heart failure (17.9%). The etiology of 48 cases (7.5%) remained uncertain. In the
      neoplastic effusion group, the most frequent locations of the primary tumor were
      lung (32.6%), breast (11.5%), lymphoma (10.8%), and ovary (7.5%); in 21 cases
      (14.3% of the neoplastic group), it was not possible to identify the primary
      tumor. The 111 patients aged younger than 40 years with tuberculous effusions
      made up 69.4% of tuberculous effusion cases and the same percentage of patients
      younger than 40 years; the proportion of effusions that were tuberculous peaked
      in the 11- to 30-year-old age group and declined steadily thereafter. Of the
      patients with neoplastic effusions, 83% were older than 50 years; the proportion
      of effusions that were neoplastic rose steadily from zero in the 0- to 30-year
      old age group to a peak among 60- to 70-year-olds. The age-wise distribution of
      effusions secondary to congestive heart failure was similar to that of neoplastic
      effusions. Of the effusions secondary to congestive heart failure, 86% (99/115)
      affected the right pleura or both, and 83% of effusions secondary to pulmonary
      thromboembolism (15/18) affected the right side. Neoplastic, tuberculous,
      parapneumonic, empyematous, and other exudative effusions showed no preference
      for either side. Of the 97 bilateral effusions, 77 (79.4%) were secondary to
      heart failure (59, 60.8%) or neoplasia (18, 18.6%). We conclude that in our
      region, the most frequent cause of pleural effusion is tuberculosis, followed by
      neoplasia and congestive heart failure. We suggest that all those interested in
      pleural disease should determine the etiologic pattern of pleural effusion in
      their region with a view to the adoption of regionally optimized diagnostic and
      therapeutic attitudes.

PMID- 8549180
TI  - Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N
      acetylcysteine.
AB  - The production of cytotoxic oxygen radicals by activated granulocytes is a
      proposed mechanism of lung injury in ARDS. Protective effects of N-acetylcysteine
      (NAC) have been described in experimental and clinical ARDS. NAC could act in
      part by replenishing the intracellular stores of glutathione (GSH) in activated
      granulocytes, leading to detoxification of oxygen radicals produced by these
      cells. To test this hypothesis, 16 patients in the early phase of ARDS were
      randomized to receive either NAC (n = 8) or placebo (n = 8); granulocyte GSH,
      granulocyte oxygen radical production, and plasma levels of granulocyte elastase
      were measured in blood samples drawn sequentially within 8 h after the onset of
      ARDS (day 0), and then 24 (day 1), 72 (day 3), and 120 h (day 5) after the first
      sample; treatment with NAC or placebo was started immediately after day 0 and
      stopped just after day 3. Granulocyte GSH was significantly higher on days 1 and
      3 when NAC was received by the patient. Unstimulated oxygen radical production,
      as measured ex vivo by luminol- and lucigenin-amplified chemiluminescence (CL),
      was higher in granulocytes from ARDS patients than from healthy control subjects,
      but was not influenced by NAC. The plasma levels of granulocyte elastase were
      five to eight times above the upper normal limit on day 0, decreased steadily
      until day 5, and were uninfluenced by NAC. In summary, parenteral NAC treatment
      started within 8 h of diagnosis increases the intracellular GSH in the
      granulocytes of ARDS patients without decreasing spontaneous oxidant production
      by these cells. The mechanisms of the protective effects of this drug previously
      reported in experimental and clinical ARDS remain to be established.

PMID- 8549181
TI  - Swallowing dysfunction in patients receiving prolonged mechanical ventilation.
AB  - Several studies have suggested that swallowing dysfunction and pulmonary
      aspiration occur in patients receiving prolonged ventilation. However, the
      incidence of swallowing dysfunction, its rate of resolution, and the sensitivity
      of tests used to characterize swallowing abnormalities are not well defined. The
      goals of our study were to evaluate swallowing function in this group of patients
      by (1) defining the specific swallowing abnormalities that occur in this patient
      population, (2) comparing the sensitivity of bedside evaluations to modified
      barium swallow with videofluoroscopy (MBS/VF), (3) performing endoscopic
      evaluation of the upper airway to characterize glottic function during
      swallowing, (4) evaluating the relationship between swallowing dysfunction and
      neuromuscular disorders, and (5) studying the temporal resolution of swallowing
      abnormalities. Swallowing function was evaluated in 35 patients receiving
      prolonged ventilation (ie, > or = 3 weeks) admitted to a specialized
      rehabilitation unit dedicated to the care of patients requiring prolonged
      ventilation. The average age of the 35 patients was 61 +/- 15 years. The total
      duration of intubation at the time of the initial swallowing evaluation was 29 +/
      34 days via a cuffed tracheostomy tube and 15 +/- 9 days via an endotracheal
      tube. Neuromuscular disorders were present in 16 patients (45%). Thirty-four
      percent of the patients had at least one swallowing abnormality detected by
      bedside examination. Results of bedside swallowing examination were abnormal in
      31% of patients with a neuromuscular disorder and 37% of patients without a
      neuromuscular disorder. MBS/VF was abnormal in 83% of patients (85% in patients
      with and 80% in patients without a neuromuscular disorder). Results of early (< 1
      month) repeated MBS/VF examinations usually remained unchanged; however, in a
      small group of patients, later studies (> or = 1 month) revealed significant
      improvement. In 50% of patients who underwent direct laryngoscopy, important
      abnormalities were found that contributed to swallowing dysfunction. Our data
      show that patients requiring prolonged mechanical ventilation have a high
      incidence of swallowing abnormalities, regardless of the presence or absence of
      neuromuscular disorders. MBS/VF and direct laryngoscopy can provide useful
      information about laryngeal action and swallowing dysfunction, and can facilitate
      the implementation of corrective actions to prevent respiratory complications.

PMID- 8549182
TI  - Pneumococcal bacteremia in two tertiary care hospitals in Winnipeg, Canada.
      Pneumococcal Bacteremia Study Group.
AB  - STUDY OBJECTIVE: To review experience with pneumococcal bacteremia at two
      Canadian tertiary care centers. DESIGN: Retrospective record review. SETTING: Two
      tertiary acute care teaching hospitals in Winnipeg, Manitoba. PATIENTS: Patients
      identified with pneumococcal bacteremia during an 8-year period. RESULTS:
      Hospital records were reviewed for 534 of 617 patients with pneumococcal
      bacteremia. The overall case fatality ratio was 70 (13%), varying from 3.2% in
      children to 43% in those older than 80 years. Twenty-seven (18%) hospitalized
      children and 68 (23%) adults required ICU admission. Duration of hospitalization
      was 14.9 +/- 24.9 and 11.0 +/- 19.1 days for children at the two institutions and
      22.5 +/- 37.6 days and 38 +/- 93 days for adults. For the 217 viable pneumococcal
      strains studied, 89% were serotypes included in the present 23-valent vaccine.
      Documentation of prior vaccination was present for only 9 (1.7%) patients,
      although 281 (89%) adults and 99 (45%) children met criteria for vaccination.
      CONCLUSIONS: Mortality in our population is similar to previous reports. More
      widespread pneumococcal vaccination in eligible populations may not only decrease
      mortality, but may also provide savings through decreased hospital admission and
      need for intensive care.

PMID- 8549183
TI  - Noninvasive positive pressure ventilation via face mask. First-line intervention
      in patients with acute hypercapnic and hypoxemic respiratory failure.
AB  - OBJECTIVES: We have previously reported our experience with noninvasive positive
      pressure ventilation (NPPV) via face mask in a small group of selected patients
      with acute respiratory failure (ARF). NPPV was frequently effective (70% success
      rate) in correcting gas exchange abnormalities and in avoiding endotracheal
      intubation (ETI); NPPV also had a low rate of complications. We have evaluated
      the clinical application of NPPV as first-line intervention in patients with
      hypercapnic and short-term hypoxemic ARF. A dedicated respiratory therapist
      conducted an educational program with physicians-in-training rotating through the
      medical ICUs of a university medical center and supervised implementation of a
      simplified management protocol. Over 24 months, 164 patients with heterogeneous
      forms of ARF received NPPV. We report on the effectiveness of NPPV in correcting
      gas exchange abnormalities, in avoiding ETI, and associated complications, in
      different conditions precipitating ARF. PATIENT POPULATION: One hundred fifty
      eight patients completed the study. Forty-one had hypoxemic ARF, 52 had
      hypercapnic ARF, 22 had hypercapnic acute respiratory insufficiency (ARI), 17 had
      other forms of ARF, and 26 with advanced illness had ARF and refused intubation.
      Twenty-five percent of the patients developed ARF after extubation. INTERVENTION:
      Mechanical ventilation was delivered via a face mask. Initial ventilatory
      settings were continuous positive airway pressure (CPAP) mode, 5 cm H2O, with
      pressure support ventilation of 10 to 20 cm H2O titrated to achieve a respiratory
      rate less than 25 breaths/min and an exhaled tidal volume of 7 mL/kg or more.
      Ventilator settings were adjusted following arterial blood gases (ABG) results.
      RESULTS: The mean duration of NPPV was 25 +/- 24 h. When the 26 patients with
      advanced illness are excluded, NPPV was effective in improving or correcting gas
      exchange abnormalities in 105 patients (80%) and avoiding ETI in 86 (65%).
      Failure to improve ABG values was the reason for ETI in 20 of 46 (43%). The
      overall average predicted and actual mortality were 32% and 16%, respectively.
      Survival was 93% in non-intubated patients and 79% in intubated patients. NPPV
      was effective in lessening dyspnea throughout treatment in all but seven
      patients. Complications developed in 24 patients (16%). In patients with
      hypercapnic ARF, nonresponders had a higher PaCO2 at entrance (91.5 +/- 4.2 vs 80
      +/- 1.5; p < 0.01). In patients with hypercapnic ARF and ARI, arterial blood
      gases response (pH and PaCO2) within 2 h of NPPV predicted success (p < 0.0001).
      None of the entrance parameters predicted need for ETI. CONCLUSIONS: We conclude
      that application of NPPV in clinical practice is an effective and safe
      alternative to ETI in many hemodynamically stable patients with hypercapnic ARF
      and in those with hypoxemic ARF in whom the clinical condition can be readily
      reversed in 48 to 72 h. An educational and supervision program is essential to
      successfully implement this form of therapy.

PMID- 8549184
TI  - Thoracoscopy for empyema and hemothorax.
AB  - Video-assisted thoracic surgery (VATS) has assumed greater importance in the
      management of pleural disease. Since 1990, we have performed VATS procedures to
      manage a variety of pathologic pleural processes in 306 patients. The 99 patients
      with complex empyemas or hemothoraces are the focus of this report. Seventy-six
      patients with complex empyemas (including 26 chronic) were approached with VATS
      after inadequate chest tube drainage. The causes associated with the thoracic
      empyemas were parapneumonic collections in 47, after hemothorax in 8, infected
      sympathetic effusions associated with intra-abdominal sepsis in 6,
      postresectional in 5, prolonged bronchopleural fistula following spontaneous
      pneumothorax in 4, chronic drainage of malignant pleural effusions in 4, and
      chronic drainage of pleural effusion in 2 patients undergoing chemotherapy. Ages
      ranged from 14 to 78 years. Sixty-three patients (83%) were treated with
      thoracoscopic drainage +/- decortication alone. Thirteen patients (17%) required
      subsequent thoracotomy for decortication, including 12 of the 26 (46%) chronic
      empyemas known to be greater than 3 weeks old. Chest tubes were removed 3.3 +/-
      2.9 days postoperatively in 67 patients; 9 patients (12%) were sent home with
      empyema tubes. Postoperative hospital stay for these patients with empyema
      averaged 7.4 +/- 7.2 days. There were five deaths, all related to progressive
      sepsis from associated pneumonia (6.6%). Twenty-three patients underwent
      thoracoscopic evacuation of hemothoraces that resulted following open heart
      surgery in 6, thoracic trauma in 7, were iatrogenic in 7, and bleeding into
      malignant effusions in 3. All were successfully treated by thoracoscopic drainage
      and pleural debridement alone. Chest tubes were removed 2.8 +/- 0.5 days
      postoperatively and hospital stay averaged 4.3 +/- 1.9 days. There were no
      complications; one patient with a hemothrax (after heart transplant) died of
      unrelated causes. In our experience, VATS has been highly successful in the early
      management of empyemas and hemothoraces. Conversion to open thoracotomy must
      always be anticipated, especially when approaching chronic empyemas.

PMID- 8549185
TI  - Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP
      in human lymphocytes.
AB  - BACKGROUND: Dopexamine and dobutamine are traditionally described as having
      primarily beta 2-adrenergic agonist properties; norepinephrine is generally
      classified as beta 1-selective; and epinephrine, isoproterenol, and dopamine are
      considered mixed beta 1- and beta 2-receptor agonists. Much of this selectivity
      is designated from studies conducted with intact cardiovascular systems in which
      indirect actions (eg, norepinephrine release from presynaptic nerve terminals)
      are not separated from direct agonist-receptor interactions. OBJECTIVE: To assess
      the relative efficacy and potency of dopamine, dobutamine, dopexamine,
      epinephrine, isoproterenol, and norepinephrine for directly stimulating cyclic
      adenosine monophosphate (cAMP) production in human lymphocytes, a model of beta 2
      adrenoceptor function. DESIGN: Open-label, prospective paired studies of
      lymphocytes from nine healthy human volunteers (seven men). SETTING: Experimental
      laboratory of a large, university-affiliated medical center. INTERVENTIONS:
      Concentration-response curves were generated for each adrenergic agonist; maximal
      cAMP production was used to compare efficacy. For the agonists that more than
      doubled basal cAMP concentrations, EC50 calculations were used to compare
      potency. MEASUREMENTS AND MAIN RESULTS: Isoproterenol and epinephrine produced
      the greatest concentrations of cAMP of the agonists tested. cAMP production was
      increased by isoproterenol at concentrations 1/10 to 1/10,000 that of the other
      agonists. Norepinephrine stimulated cAMP production only one third as much as
      epinephrine and isoproterenol, but more than double the level of dopamine,
      dobutamine, and dopexamine. EC50 concentrations for norepinephrine were 10-fold
      higher than epinephrine and 50-fold higher than isoproterenol. CONCLUSIONS:
      Epinephrine and isoproterenol are the most efficacious and potent direct-acting
      beta 2-adrenergic receptor agonists using this lymphocyte cAMP model.
      Norepinephrine exhibits significant effects on the beta-receptors on lymphocytes,
      suggesting beta 2-adrenoceptor effects with high concentrations of this drug. The
      very low cAMP levels generated by dopamine, dobutamine, and dopexamine (even in
      high concentrations) support other evidence that these agents have little direct
      effect on the beta 2-adrenoceptor.

PMID- 8549186
TI  - Video-assisted thoracoscopy. Treatment for empyema and hemothorax.

PMID- 8549187
TI  - Snoring.

PMID- 8549188
TI  - Evolving concepts regarding selection of patients for cardiac transplantation.
      Assessing risks and benefits.

PMID- 8549189
TI  - Opinions regarding the diagnosis and management of venous thromboembolic disease.
      ACCP Consensus Committee on Pulmonary Embolism.

PMID- 8549190
TI  - Coping and learning with data systems in the information age.

PMID- 8549191
TI  - Gene therapy for cystic fibrosis.

PMID- 8549192
TI  - Evaluation of effect of lung resection on lobar ventilation and perfusion using
      intrabronchial capnography.
AB  - Intrabronchial capnography was applied in 11 lung cancer patients to investigate
      the effects of lobectomy on regional lung function. Spirometry and intrabronchial
      capnography were performed before surgery (PRE), and during the early (POST1,19
      +/- 5 POD) and late (POST2, 184 +/- 98 POD) postoperative periods. End-tidal
      carbon dioxide concentration (EtCO2) and Smidt's velocity profile index (V-index)
      were calculated from each lobar capnogram obtained bronchoscopically. The V-index
      of lobes without cancer on the operated-on side increased after surgery (PRE,
      10.7 +/- 5.0%; POST1, 14.3 +/- 9.4%, NS; POST2, 16.8 +/- 8.6%, p < 0.05), while
      the V-index on the unoperated-on side decreased after surgery (PRE, 10.5 +/-
      5.3%; POST1, 7.9 +/- 3.5%, p < 0.05; POST2, 7.2 +/- 2.9%, p < 0.05). EtCO2 after
      surgery was lower on the operated-on side (POST1, 5.1 +/- 1.1%; POST2, 4.6 +/-
      1.1%) than on the unoperated-on side (POST1, 5.4 +/- 0.9%, p < 0.05; POST2, 5.0
      +/- 0.9%, p < 0.01). Since the V-index and EtCO2 are compatible with the
      expiratory flow rate and the perfusion/ventilation ratio, respectively, we
      concluded that the air flow decreased on the operated-on side and increased on
      the unoperated-on side postoperatively and that perfusion on the operated-on side
      was more severely reduced than ventilation. These findings suggest that
      intrabronchial capnography is useful for assessing the ventilation and perfusion
      of the individual lobes as single units.

PMID- 8549193
TI  - Diurnal variation of ischemic response to exercise in patients receiving a once
      daily dose of beta-blockers. Implications for exercise testing and prescription
      of exercise and training heart rates.

PMID- 8549194
TI  - What do physicians tell patients with end-stage COPD about intubation and
      mechanical ventilation?
AB  - BACKGROUND: At some point in time, many patients with end-stage COPD require
      intubation and mechanical ventilation (MV) to sustain life. MV decisions are most
      effective when the patient and physician have discussed the options in advance.
      The purpose of this study was to examine how the physician perceives the decision
      making process. METHODS: Fifteen respirologists were interviewed to elicit
      information regarding intubation and MV, and the exchange of information between
      patients and physicians. Emergent themes were coded using a qualitative approach
      and were verified by a blinded researcher. RESULTS: Respondents included ten
      academic and five community-based respirologists from seven hospitals. Most
      physicians were men with between 4 and 37 years experience. Narratives were very
      similar in content and seemed well rehearsed. Approach and delivery, however,
      were unique to each physician. Fourteen respirologists emphasized the importance
      of knowing patients as individuals prior to initiating this discussion. This
      period of familiarization often dictated when the physician believed the
      ventilation discussion is appropriate. Individual physician comfort also appeared
      to affect the timing of the discussion. Physicians discussed the many elements
      that make the MV discussion difficult for physicians and patients. Intubation
      details included a tube being placed down the throat, the discomfort associated
      with the tube, the inability to speak, and the availability of pain reducing
      medication. All physicians discussed the possibility of death with their
      patients, although many preferred euphemisms in initial discussions. All
      physicians indicated that intubation is presented as the patient's choice.
      However, all but one physician commonly framed their discussions in order to
      influence patient choice. The positive or negative framing seemed contingent on
      the physician's expectations for that patient. CONCLUSIONS: Our interviews
      demonstrated considerable agreement between physicians about the content and
      timing of the intubation MV discussion. Physicians all agreed that knowing the
      patient and his or her situation was important in determining the timing of the
      intubation and MV discussion. Practice style and individual physician comfort
      with end-of-life decisions may influence the timing of the discussion and
      possibly the number of patients who are finally approached. All physicians
      advocated a shared decision-making approach, but they strongly influence the
      deliberation process. Thus, the decision-making model seemed to be physician
      driven in this study.

PMID- 8549195
TI  - Pulmonary nodules in a patient with seminoma testis.

PMID- 8549196
TI  - Massive hemoptysis after coronary artery bypass grafting.

PMID- 8549197
TI  - Long-term survival following surgical treatment of solitary brain metastasis in
      non-small cell lung cancer.
AB  - Dissemination of lung cancer beyond the intrathoracic lymph nodes (stage IV
      disease) implies surgical unresectability. However, solitary brain metastases
      (SBMs) from non-small cell lung cancer (NSCLC) have often been treated by
      combined resection of the primary tumor and its metastasis. Such an aggressive
      approach appears to substantively improve patient outcome and provide better
      quality of life in selected cases. A search of the literature reveals extended
      survival (10 years or longer) in 16 patients following combined surgical
      excision. We report three patients with NSCLC and isolated central nervous system
      involvement who achieved exceptionally long survival. The existing literature on
      SBMs from NSCLC is reviewed.

PMID- 8549198
TI  - Pulmonary botryomycosis in a patient with AIDS.
AB  - We describe the clinical and pathologic findings of the first reported case of
      pulmonary botryomycosis in a patient with AIDS. Botryomycosis is an uncommon,
      chronic, suppurative disease that is often mistaken clinically and histologically
      for a fungal infection. The patient responded to systemic antibiotic therapy.

PMID- 8549199
TI  - Pulmonary edema following electrical cardioversion of atrial fibrillation.
AB  - A 61-year-old man with hypertrophic cardiomyopathy developed acute pulmonary
      edema 29 h following cardioversion of chronic atrial fibrillation to sinus
      rhythm. Doppler echocardiographic evaluation of atrial function showed return of
      right atrial contraction but absent left atrial systole. This has not been
      reported previously in a case of postcardioversion pulmonary edema.

PMID- 8549200
TI  - Nonfebrile mitral valve endocarditis due to Neisseria subflava.
AB  - Native valve endocarditis normally presents with fever and only later in its
      course demonstrates dysfunction of the affected valve. We describe a case of
      endocarditis due to Neisseria subflava, a Gram-negative diplococcal saprophyte of
      the oral cavity, which was unsuspected clinically and found unexpectedly during a
      mitral valve operation performed for symptomatic prolapse with regurgitation.

PMID- 8549201
TI  - Acute myocarditis and left ventricular aneurysm as presentations of systemic
      lupus erythematosus.
AB  - A case of systemic lupus erythematosus (SLE) associated with fever, heart
      failure, and left ventricular (LV) aneurysm is reported. A diagnosis of SLE was
      suspected owing to the presence of active lymphocytic myocarditis and fibrinous
      endocarditis at LV endomyocardial biopsy and was confirmed by identification of 4
      of the 11 criteria proposed by the American Rheumatism Association for the
      definition of SLE. A 2-month period of steroid therapy was followed by a
      remarkable recovery of LV function and progression of endomyocarditis to a healed
      phase at control LV biopsy. The LV aneurysm disappeared, likely because
      thrombosis occurred as a result of the hypercoagulable state accompanying the
      presence of anticardiolipin antibodies. This is the first reported case of LV
      aneurysm induced by SLE and is a rare clinicohistologic documentation of the
      effectiveness of steroid treatment on lupus endomyocarditis.

PMID- 8549202
TI  - Complex pleural effusion associated with a subphrenic gallstone phlegmon
      following laparoscopic cholecystectomy.
AB  - A 90-year-old man presented with a large right-sided complex pleural effusion 4
      months after a laparoscopic cholecystectomy. An initial thoracic CT scan
      confirmed the presence of the effusion, and the results of thoracentesis on three
      separate occasions were consistent with an exudative process. Another CT scan of
      the chest with thin-section cuts through the diaphragm along with an abdominal
      ultrasound revealed a retrohepatic subdiaphragmatic gallstone collection that
      eroded into the right hemidiaphragm. Thoracoscopic evacuation of the phlegmon,
      removal of the spilled gallstones, and repair of the diaphragm resulted in
      resolution of the effusion.

PMID- 8549203
TI  - Anomalous systemic arterial supply to normal basal segments of the left lower
      lobe. A report of two cases.
AB  - Two cases of anomalous systemic arterial supply to the basal segments of the
      lower lobe of the left lung without sequestration are presented. In the first
      case, the final diagnosis was made during a surgical operation, and lobectomy of
      the lower lobe of the left lung was performed. In the second case, the
      preoperative diagnosis made by CT was confirmed by angiography. An anastomosis
      was performed between the anomalous artery and the pulmonary artery without
      resection of the basal segments. Six months after surgery, pulmonary angiography
      showed improved flow of the anastomosed vessel, but little improvement was
      evidenced in the perfusion scan.

PMID- 8549204
TI  - Subacute tricuspid regurgitation with severe hypoxemia complicating blunt chest
      trauma.

PMID- 8549205
TI  - Lactic acidosis associated with propofol.

PMID- 8549206
TI  - Bronchodilating effects of combined therapy with clinical dosages of ipratropium
      bromide and salbutamol for stable COPD.

PMID- 8549207
TI  - On "Who will teach the medical students".

PMID- 8549208
TI  - Bronchodilating effects of combined therapy with clinical dosages of ipratropium
      bromide and salbutamol for stable COPD.

PMID- 8549209
TI  - Not all pulmonary embolism tests survive utilization.

PMID- 8549210
TI  - Thrombolysis and the elderly.

PMID- 8549211
TI  - Cardiac rehabilitation in obese patients.

PMID- 8549212
TI  - Iatrogenic serratus anterior paralysis. Long-term outcome in 26 patients.
AB  - STUDY OBJECTIVE: To evaluate the treatment, extent of recovery, and residual
      disability in 26 iatrogenic cases of serratus paralysis. PATIENTS AND STUDY
      DESIGN: Seventeen cases of serratus anterior paralysis had occurred following a
      local invasive procedure along the course of the long thoracic nerve, including
      seven first-rib resections, four mastectomies with axillary dissection, two
      scalenotomies, two surgical treatments of spontaneous pneumothorax, and two
      infraclavicular plexus anesthesia. Eight cases of paralysis had occurred after
      general anesthesia for patients who had undergone surgery for diverse clinical
      reasons. One case of paralysis occurred after spinal anesthesia. The length of
      sick leave, treatment with a shoulder brace, amount of physical therapy, long
      term symptoms, and residual disability were evaluated from the medical records
      and from the questionnaire sent to the patients on average 6 years (range, 2 to
      11 years) after the onset of the paralysis. RESULTS: Despite comprehensive and
      lengthy treatment, all but one had residual symptoms, as well as limitations in
      the use of the affected limb. Twenty-one (81%) of the patients could not lift or
      pull heavy objects, 15 (58%) could not play sports, such as tennis or golf, and
      14 (54%) found it impossible to work with hands above shoulder level. CONCLUSION:
      Serratus anterior paralysis, following anesthesia or local invasive procedures on
      the anterolateral aspect of the thorax, may cause considerable and long-term
      dysfunction of the shoulder girdle and affect the function of the whole upper
      limb.

PMID- 8549213
TI  - Mitral valve reconstruction in elderly, ischemic patients.
AB  - The role of mitral valve reconstruction is controversial in elderly patients with
      concurrent ischemic heart disease owing to technical difficulty, prolonged
      operative times, high mortality, and possible residual mitral regurgitation.
      However, mitral reconstruction could be most beneficial in this age group due to
      preservation of left ventricular function, avoidance of anticoagulation, or
      repeat operation for bioprosthetic degeneration. We studied the outcome of mitral
      valve reconstruction in 100 consecutive elderly ischemic patients 65 years or
      older (mean = 73 years; range, 65 to 86 years) operated on between October 1990
      and May 1995. Preoperatively all patients were New York Heart Association (NYHA)
      class III or IV with an ejection fraction of 32 +/- 2%. All patients underwent
      primary coronary bypass grafting (2.7 +/- 0.2 grafts) and had a flexible mitral
      annuloplasty ring inserted. Additionally, 54 patients required further complex
      mitral repairs. All patients had 4+ mitral regurgitation by transesophageal
      echocardiography prior to operation. After mitral reconstruction, no patient had
      more than 1+ regurgitation, while most had none and no systolic anterior leaflet
      motion was noted. There were 4 early (30 day) deaths (4%) and 6 late deaths (6%)
      at a mean follow-up of 25 months. Patient morbidity has included episodes of mild
      congestive heart failure (nine), transient ischemic attack (one), endocarditis
      (one), and respiratory failure (five). There have been one early and two late
      reoperations for mitral valve replacement. All remaining patients are in NYHA
      class I or II. While longer-term follow-up is mandatory, coronary bypass grafting
      and mitral valve reconstruction in the elderly can be accomplished with
      acceptable surgical mortality and morbidity, yielding reliable improvement in
      symptoms and quality of life.

PMID- 8549214
TI  - Adenosine is a selective pulmonary vasodilator in cardiac surgical patients.
AB  - OBJECTIVE: The purpose of this study was to examine and compare the systemic and
      pulmonary hemodynamic effects of a central venous infusion of adenosine in
      cardiac surgical patients. DESIGN: Prospective; each subject served as his/her
      own control. SETTING: University Hospital and Veteran's Affairs Medical Center.
      PATIENTS: Ten cardiac surgical patients (age 56 +/- 6 years) were studied in the
      operating room under general anesthesia after weaning from cardiopulmonary
      bypass. Pulmonary vascular resistance (PVR), systemic vascular resistance (SVR),
      mean pulmonary arterial pressure (MPAP), and mean systemic arterial pressure
      (MAP) were determined before, during, and after central venous infusion of
      adenosine (50 micrograms/kg/min) for 15 min. Statistical analysis was by analysis
      of variance; significance was accepted at p < 0.05. RESULTS: Adenosine produced
      selective vasodilation of the pulmonary vascular bed: both PVR and MPAP were
      significantly reduced during adenosine infusion without changes in either SVR or
      MAP. PVR and MPAP returned to preinfusion levels after cessation of the infusion.
      Adenosine effectively reduced PVR and pulmonary arterial pressure without
      decreasing SVR or systemic arterial pressure. CONCLUSIONS: Adenosine may be used
      clinically as a selective pulmonary vasodilator to optimize pulmonary
      hemodynamics without adverse systemic hemodynamic effects in cardiac surgical
      patients. It may be particularly valuable in patients with right heart
      dysfunction by selectively lowering right ventricular afterload.

PMID- 8549215
TI  - Further increase in oxygen uptake during early active recovery following maximal
      exercise in chronic heart failure.
AB  - STUDY OBJECTIVE: Some patients with chronic heart failure manifest a further
      increase in oxygen uptake (VO2) after maximal exercise whereas others do not. The
      purpose of this study was to determine the characteristics of chronic heart
      failure patients with further increase in VO2 in early active recovery following
      maximal exercise. DESIGN: Retrospective analysis of clinical and exercise testing
      characteristics in patients with or without a further increase in VO2 during
      early active recovery. PATIENTS: One hundred forty-two patients with a history of
      congestive heart failure and left ventricular ejection fraction of 45%, or less
      who performed a symptom-limited graded treadmill exercise test. MEASUREMENTS AND
      RESULTS: Expired gases were monitored breath by breath from rest throughout
      exercise and during 1 min of active recovery. Patients were defined as having a
      further increase in VO2 if the average VO2 during the initial 30 s of active
      recovery was greater than or equal to VO2 during the final 30 s of graded
      exercise and the instantaneous VO2 (from the breath-by-breath plot) at 30 s of
      active recovery was greater than or equal to the instantaneous VO2 at peak
      exercise. Thirty patients (21%) showed a further increase in VO2 following peak
      exercise (group 1), and 112 had decreased VO2 at 30 s after peak exercise (group
      2). In group 1, treadmill time was significantly shorter, peak VO2 was
      significantly lower (16.6 +/- 3.6 vs 21.6 +/- 6.4 mL/kg/min), and peak
      ventilatory equivalent for carbon dioxide (VE/VCO2) was significantly higher than
      those in group 2. There was no difference in etiology of heart failure or
      functional class and medication status. CONCLUSION: A further increase in VO2
      during early active recovery was associated with poorer exercise tolerance, lower
      peak VO2, and higher peak VE/VCO2 in chronic heart failure patients. This sign
      may be a new functional variable for assessment of chronic heart failure. Further
      investigations are warranted to clarify the mechanisms and clinical implications
      of this phenomenon.

PMID- 8549216
TI  - Noninvasive testing in the diagnosis of pulmonary embolism. PIOPED revisited.

PMID- 8549217
TI  - Effects of cardiac rehabilitation and exercise training in obese patients with
      coronary artery disease.
AB  - STUDY OBJECTIVE: To determine the effects of cardiac rehabilitation and exercise
      training in obese coronary patients. DESIGN: We compared data before and after
      cardiac rehabilitation between obese and nonobese patients. SETTING: Two large
      teaching institutions. PATIENTS: 116 obese (body mass index [BMI] > or = 27.8
      kg/m2 for men and > or = 27.3 kg/m2 for women; mean, 31.2 +/- 3.2 kg/m2] and 198
      (mean BMI, 24.6 +/- 2.1 kg/m2) nonobese patients with recent cardiac events.
      INTERVENTIONS: A 3-month (36-session) formal, outpatient phase 2 cardiac
      rehabilitation and supervised exercise training program. MEASUREMENTS AND
      RESULTS: At baseline, obese patients had higher levels of total cholesterol (p <
      0.01), low-density lipoprotein-cholesterol (LDL-C [p < 0.01]), LDL-C/high-density
      lipoprotein cholesterol (HDL-C) ratio (p < 0.01), percentage body fat (p < 0.02),
      and a higher prevalence of hypertension (p < 0.05) than the nonobese patients,
      but the prevalence of diabetes mellitus and of other coronary risk factors was
      similar. After cardiac rehabilitation, there were modest reductions in the
      prevalence of obesity (116 patients [37%] vs 104 patients [33%]) and severe
      obesity (BMI > or = 35 kg/m2 [3.5 vs 2.5%]), although these improvements were not
      statistically significant. The obese patients had improvements in exercise
      capacity (+24%; p < 0.001), BMI (-3%; p < 0.0001), LDL-C (-4%; p = 0.07), HDL-C
      (+6%; p < 0.001), and LDL-C/HDL-C ratio (-10%; p < 0.01). Although reduction in
      BMI was greater in the obese patients (-3 vs 0%; p < 0.0001), improvement in
      exercise capacity was greater in the nonobese (+36 vs +24%; p < 0.01);
      improvements in lipid fractions and percentage body fat were statistically
      similar between the groups. CONCLUSION: Modest reductions in BMI, obesity, and
      severe obesity occur after cardiac rehabilitation. In addition, obese patients
      demonstrate significant improvements in most coronary risk factors after
      rehabilitation, although improvements in exercise capacity are greater in
      nonobese patients. Potentially, more significant improvements in exercise
      capacity and lipid values may occur by specifically targeting obese patients for
      further weight reduction and exercise training after major cardiac events.

PMID- 8549218
TI  - Impaired cardiopulmonary exercise capacity in patients with hyperthyroidism.
AB  - STUDY OBJECTIVE: Hyperthyroidism (H) has been implicated as a primary cause of
      decreased exercise tolerance. To our knowledge, analysis of respiratory gas
      exchange, an efficient noninvasive method in evaluating cardiopulmonary capacity,
      has not been performed in patients with H. PATIENTS: Using cardiopulmonary
      exercise testing, 12 consecutive women with Graves' H were examined and
      controlled in euthyroidism (E). Eighteen women with E, in whom cardiac
      catheterization had ruled out heart disease, served as control subjects (C).
      MEASUREMENTS: The ventilatory anaerobic threshold was determined by means of the
      V-slope method. Ergometry was performed with patients in a semisupine position
      using a continuous ramp protocol of 20 W/min. Echocardiography at rest was
      performed in all patients. RESULTS: In patients with H, heart rate at rest was
      higher than in patients with E (p < 0.05) and showed a markedly lower increase
      between rest and anaerobic threshold compared with E patients (p = 0.007) and C
      (p = 0.009). Work rate was reduced (H, 50% vs E, 70%; p = 0.038). In H patients,
      the anaerobic threshold occurred at 59.6% of maximal oxygen uptake and 72% in E
      patients, respectively (p = 0.024). In H patients, the linear regression of the
      heart rate to oxygen uptake ratio showed a reduced slope in comparison with E
      patients (p = 0.001) and C (p = 0.004). In patients with H, a reduced tidal
      volume (p = 0.021) and an increased respiratory rate (p = 0.003) in comparison to
      patients with E were demonstrated. Echocardiographically, H patients had an
      increased ejection fraction (p = 0.008) and a higher cardiac index (p = 0.008) in
      comparison with E patients. CONCLUSIONS: Analysis of respiratory gas exchange
      showed marked alterations of cardiopulmonary exercise capacity in H patients,
      which are reversible in E patients. The impaired chronotropic response during
      exercise might be the primary limiting factor of reduced work capacity in
      patients with H.

PMID- 8549219
TI  - Intermittent pneumatic compression for the prevention of venous thromboembolism.

PMID- 8549220
TI  - Doppler echocardiographic detection of left ventricular diastolic dysfunction in
      patients with pulmonary sarcoidosis.
AB  - STUDY OBJECTIVE: To determine the prevalence of left ventricular diastolic
      dysfunction in patients with biopsy specimen-proved pulmonary sarcoidosis without
      clinical evidence of cardiac disease. DESIGN: A cross-sectional study. SETTING: A
      large tertiary care university teaching hospital. PATIENTS AND CONTROL SUBJECTS:
      Fifty consecutive subjects had biopsy specimen-proved pulmonary sarcoidosis
      without suspected cardiac involvement. Those with other conditions known to
      affect diastolic function were excluded. The control group comprised 30 healthy
      hospital workers. INTERVENTIONS: Clinical examination, 12-lead ECG, and combined
      echocardiographic/phonocardiographic examination. MEASUREMENTS: Indexes of left
      ventricular diastolic function, including isovolumic relaxation time, peak
      velocity of early (E) and late (A) ventricular filling, deceleration rate of
      early diastolic flow, and the sum of the time velocity integrals of E and A were
      obtained in each patient and control subject. Systolic function was determined
      using a modification of Simpson's rule. RESULTS: Diastolic dysfunction was
      present in 7 (14%) patients, 6 of whom had normal systolic function and normal
      two-dimensional echocardiographic examination. Those with diastolic dysfunction
      had a longer duration of illness (15 +/- 7 vs 6 +/- 5 years; p = 0.0004), were
      significantly older (52 +/- 11 vs 38 +/- 9 years; p = 0.0009), and had higher
      systolic BP (130 +/- 13 vs 117 +/- 12 mm Hg; p = 0.01) than the sarcoid patients
      with normal diastolic function. CONCLUSIONS: These results demonstrate a
      significant prevalence of left ventricular diastolic dysfunction in patients with
      pulmonary sarcoidosis. The cause of this abnormality may be a subclinical sarcoid
      cardiomyopathy.

PMID- 8549221
TI  - Noninvasive assessment of right heart function by 81mKr equilibrium radionuclide
      ventriculography in chronic pulmonary diseases.
AB  - Noninvasive multigated equilibrium radionuclide ventriculography with krypton-81m
      (81mKr) was used to assess right heart relaxation in patients with chronic
      pulmonary diseases (CPD). The subjects consisted of 30 patients with CPD and 8
      patients free of cardiopulmonary diseases admitted to our department. A region of
      interest (ROI) was selected on both the right atrium (RA) and right ventricle
      (RV). A time activity curve was obtained for each ROI. As a diastolic index of
      the right heart performance, the right atrial early emptying rate (RAER) was
      obtained from the right atrial time activity curve, while the right ventricular
      rapid filling rate (RVRFR) was obtained from the right ventricular time activity
      curve. The mean RAER was significantly lower in CPD patients compared with the
      control (CPD, 9.5 +/- 4.5; control, 16 +/- 3.4%/100 ms). Similarly, the mean
      RVRFR was significantly lower in CPD patients compared with the control (CPD,
      27.3 +/- 9.9; control, 34 +/- 8.5%/100 ms). A strong negative correlation was
      noted between the mean pulmonary arterial pressure (mPAP) and RAER (r = -0.77; p
      < 0.001) and between the mPAP and the RVRFR (r = -0.63; p < 0.001). Our results
      suggest that RAER and RVRFR measured by 81mKr are clinically useful in the
      noninvasive assessment of right heart relaxation in patients with CPD.

PMID- 8549222
TI  - The usefulness of transesophageal echocardiography in diagnosing cardiac
      contusions.
AB  - OBJECTIVES: To assess the usefulness of transesophageal echocardiography in
      diagnosing cardiac contusions in patients with blunt trauma. BACKGROUND: For more
      than a decade, noninvasive tests, including ECGs, cardiac enzymes, nuclear
      studies, and transthoracic echocardiography have been utilized in an attempt to
      identify trauma patients with cardiac injuries. These tests have been imperfect
      in identifying the patients at high risk for mortality. METHODS: We
      retrospectively reviewed the charts in 22 patients with transesophageal
      echocardiographically diagnosed cardiac contusions noting age, race, sex,
      transthoracic echocardiographic examinations, study quality, and outcome. We also
      noted the Injury Severity Score, which is a measure of the severity of illness in
      trauma patients. Higher scores correlate more severe injury and higher mortality.
      We defined cardiac contusions as presence of wall motion abnormality, including
      either or both ventricles, in the absence of transmural myocardial infarction on
      ECG following nonpenetrating chest trauma. RESULTS: Over a 30-month period, 81
      transesophageal echocardiographic examinations were performed on trauma patients.
      Among this group, 22 patients were diagnosed as having cardiac contusions. There
      were 15 patients with right ventricular contusions, 7 patients with left
      ventricular contusions, and 2 patients with both ventricles involved. We compared
      this group with all ICU trauma patients admitted to the hospital during this time
      period. Overall, the contusion patients had an average Injury Severity Score of
      27 and a mortality of 27% compared with the overall trauma group with an Injury
      Severity Score of 33 and a corresponding mortality of 9% (p < 0.001).
      Corresponding ECGs were nondiagnostic in 73% of patients with cardiac contusion.
      There were no complications related to the transesophageal examinations.
      CONCLUSIONS: Transesophageal echocardiographically diagnosed cardiac contusion in
      trauma patients carries a high mortality rate. Transesophageal examinations are
      safe and provide excellent quality images where transthoracic examinations were
      inadequate. Right ventricular contusions are approximately twice as common as
      left ventricular contusions.

PMID- 8549223
TI  - Arterial blood gas analysis in the assessment of suspected acute pulmonary
      embolism.
AB  - PURPOSE: The utility of arterial blood gas levels in excluding the diagnosis of
      acute pulmonary embolism (PE) was evaluated. METHODS: Data are from the
      Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). PE was
      diagnosed or excluded by pulmonary angiography. Among 330 patients with no prior
      cardiopulmonary disease, 130 patients had PE and 200 did not. Among 438 patients
      with prior cardiopulmonary disease, 147 had PE and 291 did not. Definitions were
      low PaO2 (< 80 mm Hg), low PaCO2 (< 35 mm Hg), and high alveolar-arterial oxygen
      gradient (P(A-a)O2 [> 20 mm Hg]). RESULTS: Among patients with no prior
      cardiopulmonary disease who had values of the PaO2 and PaCO2 that were not low
      and a P(A-a)O2 that was normal, 16 of 42 or 38% (95% confidence interval [CI] =
      24 to 54%) had PE. Among patients with prior cardiopulmonary disease who had PaO2
      and PaCO2 values that were not low and a P(A-a)O2 that was normal, 4 of 28 or 14%
      (95% CI = 4 to 33%) had PE. Other combinations of blood gas levels and the P(A
      a)O2 gradient, failed to exclude PE in larger percentages of patients.
      CONCLUSION: With various combinations of the PaO2 of 80 mm Hg or more, the PaCO2
      of 35 mm Hg or higher, and the P(A-a)O2 gradient of 20 mm Hg or less, PE could
      not be excluded in more than 30% of patients with no prior cardiopulmonary
      disease and PE could not be excluded in more than 14% of patients with prior
      cardiopulmonary disease. Blood gas levels, therefore, are of insufficient
      discriminant value to permit exclusion of the diagnosis of PE.

PMID- 8549224
TI  - The efficacy of pneumatic compression stockings in the prevention of pulmonary
      embolism after cardiac surgery.
AB  - INTRODUCTION: Pneumatic compression stocking (PCS) devices have been introduced
      to decrease the incidence of postoperative deep venous thrombosis (DVT). However,
      their role in the prophylaxis against pulmonary embolism (PE) remains unclear.
      This study was undertaken to compare the prophylactic effectiveness of
      subcutaneous heparin (SCH) alone vs the combined use of PCS and SCH in the
      prevention of PE following cardiac surgery. METHODS: We studied 2,551 consecutive
      patients who underwent cardiac surgery over a 10-year period. They were randomly
      allocated to two groups. Group A included 1,196 patients who were treated with
      5,000 U of SCH every 12 h and group B included 1,355 patients treated with a
      combined prophylactic regimen of PCS and SCH. RESULTS: The diagnosis of PE was
      established in 69 patients by either high-probability ventilation perfusion scan,
      pulmonary angiogram, or autopsy. The incidence of PE in group A patients was 4%
      (48/1,196) and in group B was 1.5% (21/1,355). The concomitant use of bilateral
      PCS and SCH reduced the frequency of postoperative PE in 62% in comparison to the
      prophylaxis with SCH alone (p < 0.001). CONCLUSIONS: These data suggest that the
      combined prophylactic method of bilateral PCS and SCH is superior to SCH alone in
      the prevention of PE after cardiac surgery.

PMID- 8549226
TI  - Does asthma education change behavior? To know is not to do.

PMID- 8549225
TI  - Assessment of practical knowledge of self-management of acute asthma.
AB  - AIMS: To develop an instrument for the measurement of, and to determine the level
      of, practical knowledge of self-management of acute asthma. METHODS: Eighty
      patients with moderate/severe asthma attending a hospital-based asthma clinic
      responded to an interviewer-administered questionnaire. Subjects were asked to
      describe the action they would take in response to each of two hypothetical
      evolving attacks: (1) one of gradually increasing severity and (2) the other
      developing rapidly. Responses were scored according to the appropriateness of
      actions taken relevant to the stage of the attack. Transcripts of the responses
      were scored independently by three of the investigators according to a system
      based on Thoracic Society of Australia and New Zealand (TSANZ) and British
      Thoracic Society (BTS) consensus statements on asthma management. A 25-point
      scale was used on which 0 represented a total lack of appropriate responses and a
      score of 25 was an optimal response. RESULTS: Interrater and intrarater
      reliability were excellent. Mean (+/- SD) scores for the slow and rapid onset
      attacks were 12.8 +/- 4.0 and 13.9 +/- 4.8, respectively. The scores for the two
      scenarios were predicted by each other (p = 0.002) and by the interviewer's
      rating of asthma management knowledge (p = 0.0004, p = 0.0001), but not by age,
      sex, race, previous asthma morbidity, depression, or anxiety. In both scenarios,
      most patients indicated that they would increase inhaled beta-agonist (85% for
      slow-onset scenarios and 94% for rapid-onset scenarios, respectively) and use
      their action plan and/or seek urgent medical advice at an appropriate time (74%
      and 70%). Although some would measure peak expiratory flow (PEF) initially (54%
      and 30%), only a minority would continue to monitor PEF in the context of
      worsening acute asthma (30% and 24%). When a severe life-threatening situation
      was described, only 50% and 64%, respectively, indicated that they would call
      emergency services. CONCLUSIONS: Scenarios describing hypothetical asthma attacks
      are a useful and reproducible method of assessing practical knowledge of self
      management of acute asthma. Patients presented with scenarios frequently made
      errors in their hypothetical responses. The errors made with scenarios, which
      parallel errors reported in real clinical situations, occurred despite the fact
      that this patient population had received considerable education and training
      about how to manage asthma. Most indicated they would not monitor PEF even in an
      exacerbation of asthma and would not call emergency services despite life
      threatening asthma. These scenarios may allow us to explore the gap between
      knowledge about treatment and actual practice, and perhaps to help close that gap
      and thus reduce asthma morbidity and mortality.

PMID- 8549227
TI  - Parents' evaluations of wheezing in their children with asthma.
AB  - OBJECTIVE: Wheezing is a widely used physical sign of asthma that physicians
      assess in evaluation of their asthmatic patients. It may be possible to teach the
      parents to recognize it and to assess its severity so as to help them make better
      informed judgment in monitoring their children with asthma. STUDY DESIGN: Parents
      were taught to recognize wheezing by placing their ear over the chest and in
      front of the open mouth of their child. One session lasting a few minutes was
      sufficient for teaching. Subsequently, the parent and a physician evaluated the
      child independently for the presence and the severity of wheezing categorized as
      easily, barely, and none detected, and results were compared. Severity of
      wheezing was also compared with peak expiratory flow rate (PEFR) whenever
      possible. RESULTS: Six hundred thirty-six observations were made in 89 parent
      child pairs. Wheezing was detected by the physician in 64% of examinations and by
      the parents in 56% (p < 0.001 by chi 2). When the physician heard the wheezing
      easily on 240 occasions, the parents also heard it in 99%. When the physician
      heard the wheezing barely on 170 occasions, the parents heard it only on 68% of
      the time. Mean PEFR was 55% predicted when the parents heard the wheezing easily,
      75% when heard barely, and 93% when not heard (the difference is significant, p <
      0.001 by analysis of variance). CONCLUSIONS: Parents can be taught to detect
      wheezing in their child with considerable accuracy when it is easily detectable
      to a physician. Such skills should be helpful to the parents in monitoring their
      child with asthma and in deciding when to increase medications and when to seek
      emergency care.

PMID- 8549228
TI  - Soluble intercellular adhesion molecule 1 (ICAM-1) antigen in sera of bronchial
      asthmatics.
AB  - Previous studies have suggested that intercellular adhesion molecule 1 (ICAM-1,
      CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form
      of ICAM-1 (sICAM-1) has been detected in increased concentrations in the sera of
      patients with certain inflammatory conditions. To determine whether bronchial
      asthma is associated with increased levels of sICAM-1 in serum and to assess the
      effects of therapy on these levels, the concentrations of sICAM-1 were measured
      in sera of healthy donors and asthmatic patients. The mean (+/- SD) level of
      serum sICAM-1 for 60 asthmatic patients (304.0 +/- 82.5 ng/mL) was significantly
      higher than that for 39 healthy volunteers (260.9 +/- 67.2 ng/mL; p = 0.004).
      Twenty-two patients considered to have atopic asthma and 24 patients with
      nonatopic asthma did not differ in their levels of sICAM-1. In 14 patients, serum
      concentrations of sICAM-1 were higher during asthma attacks than in the same
      patients during remission (p = 0.035). Serum sICAM-1 levels were lower in nine
      patients during treatment with oral prednisolone (2.5 to 40 mg/d) than during
      periods without systemic corticosteroid therapy (p = 0.002). Thus, active
      bronchial asthma is associated with the presence of increased levels of sICAM-1
      in serum, and these levels may be modulated by corticosteroid therapy.

PMID- 8549229
TI  - Pharmacokinetics of intravenously administration of prednisolone in the horse as
      determined by radioimmunoassay.
AB  - A radioimmunoassay was developed for prednisolone using IgG purified from rabbit
      antiserum. The assay was employed to determine the pharmacokinetics of
      prednisolone following intravenous administration of 450 mg of prednisolone
      sodium succinate (Solu Delta Cortef) to five adult Thoroughbred horses. The RIA
      had a sensitivity of 2 ng/ml and was relatively specific. It had cross-reactivity
      with 21-deoxycortisol (83.3%) cortisol (27.8%), 11-beta-hydroxyprogesterone
      (39.2%) and 17-hydroxyprogesterone (50%). However, it did not cross-react with
      naturally occurring steroids (cholesterol, testosterone, estradiol or
      progesterone) or synthetic steroids (betamethasone, methylprednisolone,
      prednisone or triamcinolone). Radioimmunoassay of the horse serum samples
      detected the presence of prednisolone for 5 to 7 hours post administration. The
      pharmacokinetic parameters tested and their means were a half-life of 1.150 +/-
      0.233 (+/- SEM) hours, an excretion constant of 0.686 +/- 0.018 Ke/hr, a volume
      of distribution of 607 +/- 109 ml/kg, and a clearance rate of 374 +/- 47
      ml/hr/kg. RIA also detected the presence of prednisolone in the urine beginning
      one hour post administration. The prednisolone in the urine increased
      significantly at 2 hours and reached a peak at 4 hours post administration. The
      urinary levels decreased at 5, 6, and 7 hours and peaked again at 8 hours. The
      level then gradually decreased and reached the minimal detectable levels in 48
      hours. These results showed that the RIA was sensitive and relatively specific
      for the determination of prednisolone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549230
TI  - Dissociation of the restoration of copulatory behavior and the testicular
      morphology in old male rats with fetal brain grafting.
AB  - Improvement of copulatory activity has been reported in aged male rats bearing
      the fetal preoptic area (POA), however, whether the fetal POA graft has any
      effect on the gonad of aged male rats has not been established. In the present
      study, the testicular histology and the sexual behavior were studied in 20 old
      (18-19 months) Long-Evans male rats after fetal brain transplantation. Animals
      were divided into three groups: (1) POA-grafted group (n = 6): fetal POA neurons
      were grafted into the POA, (2) COR-grafted group (n = 7): fetal cerebral cortex
      tissue was grafted into the POA and (3) SHAM-grafted group (n = 7): the POA of
      rats received glucose-saline injection. Thirty days after the grafting, only
      those bearing POA graft showed an increase in mount frequency and intromission
      frequency. Sixty days after fetal brain grafting, testicular morphology was
      examined. Testicular volume was measured and paraffin sections (8 microns) of the
      testis were stained with Hematoxylin-Eosin. Seminiferous tubular diameter and
      epithelial height were analyzed quantitatively. No significant changes in
      testicular volume, seminiferous tubular diameter and epithelial height were
      observed in all three groups. The shrunk testicular morphology in the aged male
      rats cannot be restored by fetal POA grafting. These results suggest that
      copulatory behavior and testicular morphology may be dissociated in old male
      rats.

PMID- 8549231
TI  - Serum activity of angiotensin converting enzyme (ACE) is not affected by
      hepatitis B viral infection.
AB  - Activity of angiotensin converting enzyme (ACE) in the serum from healthy and
      hepatitis B-infected subjects were examined. Preservation of the serum samples
      for 32 days at -80 degrees C did not significantly alter the activity of ACE. We
      have determined the ACE activity in three groups: healthy subjects with negative
      hepatitis B surface antigen (HBsAg) and normal liver function or the (-,N) group,
      subjects exhibiting positive HBsAg and normal liver function or the (+,N) group,
      as well as subject with positive HBsAg and abnormal liver function or the (+,Ab)
      group. The healthy group (-,N) exhibited serum activity of ACE of 31.5 +/-
      1.2(25) nmoles/min/ml serum. There was no difference in ACE activity whether
      surface antigen was present, i.e., between (-,N) and (+,N) groups. Although a
      slight (about 10%) elevation of ACE activity was observed in the third group
      (+,Ab), it was not significantly different from either (-,N) or (+,N) group.
      These results suggest the lack of association between the serum activity of ACE
      and hepatis B, however, further studies are required to clarify whether
      correlation exists between serum activity and liver function.

PMID- 8549232
TI  - Effects of aprotinin on renal function in chronic hypoxic rats.
AB  - The effect of aprotinin, a nonspecific kallikrein inhibitor on renal function was
      studied in chronic hypoxic rats (high altitude, HA), comparing to control rats
      kept at sea level (SL). Hypoxia was induced by placing female Wistar rats (195
      230 g) in an altitude chamber (5,500 m) 15 hr per day for 4 weeks. Intrarenal
      arterial administration of aprotinin (300 kiu/kg/min), reduced the urinary
      kallikrein activity (UKA) in 9 SL and 10 HA anesthetized rats. Aprotinin did not
      significantly alter the urinary excretion of urine, sodium and potassium in SL
      rats, however, those parameters increased after aprotinin administration in HA
      rats. These data support the hypothesis that kallikrein participates in the
      regulation of renal function in chronic hypoxic rats.

PMID- 8549233
TI  - Spinal pathways of nociceptive information evoked by short CO2 laser pulse in
      rats.
AB  - This study aimed to determine the relative importance of several spinal ascending
      pathways in conveying laser pulse activated A-delta and C-fiber information by
      using both awake and anaesthetized rats. Rats were subjected to spinal cord
      lesion (between T10-T12) under general anesthesia. Three types of lesion were
      made; dorsal column (DC, n = 4), bilateral dorsal lateral funiculus lesion (DLF,
      n = 4), and bilateral ventral quandrant lesion (VQ, n = 3). In normal awake rats,
      a laser pulse (10 watts intensity and 10 ms duration) applied to the plantar
      surface of the hind foot could evoke two prominent cortical potentials, one early
      and one late component in the contralateral somatosensory cortex. The early
      negative potential had a latency of 52.8 +/- 6.8 ms (mean +/- S.E.M.) and
      amplitude of 0.066 +/- 0.011 mV, while the late component had a latency of 264.6
      (4.6 ms and an amplitude of 0.143 +/- 0.014 mV. After DC lesion, only latency of
      the early response was significantly lengthened (p < 0.05). Latency and amplitude
      of the early response were reduced markedly (p < 0.01) after bilateral DLF
      lesion. The change in the late response was significant only in the latency (p <
      0.01). The peak amplitude of both early and late responses decreased
      significantly (p < 0.01) after VQ lesion. In rats with acute preparation, both of
      the DC and DLF lesions had no significant effect on the laser-evoked late
      response. The lesion of the VQ completely eliminated the late response.

PMID- 8549234
TI  - The effects of Qi-Qong ocular exercise on accommodation.
AB  - Visual-training methods in management of myopia are suggested as possibly leading
      to normal vision or an improvement in the refractive state. The purpose of this
      work was to investigate the hypothesis that a Qi-Qong ocular exercise improves
      visual function by training the accommodation bias. Variations of pupil size,
      accommodative amplitude, latency and speed of accommodative response and
      accommodative adaptation were evaluated objectively. The accommodative state was
      monitored with an objective infrared refractometer (Nidek AA-2000). Subjects were
      divided into two groups: experimental (n = 9), and control (n = 8). Subjects of
      the experimental group undertook the Qi-Qong ocular exercise for at least three
      years, and were able to perform the exercise smoothly and gently. Subjects of the
      control group had no knowledge of the Qi-Qong ocular exercise, but were given the
      same testing procedures as the experimental group. Results showed that Qi-Qong
      ocular exercise can improve the accommodative amplitude and accelerate the
      accommodative response slightly, but there was no effect on the latency of
      accommodative response. Furthermore, the level of accommodative adaptation was
      elevated, and the pupil became slight miotic. Therefore, the mechanism of visual
      improvement may undergo a great accommodative adaptation and produce a pinhole
      effect by miosis of the pupil. Methods of visual training can produce a false
      image of visual improvement from an enhanced parasympathetic response to a task,
      but this effect may be a factor that induces progression of myopia.

PMID- 8549235
TI  - Correlation of esophageal manometry and radionuclide esophageal transit in normal
      subjects.
AB  - What was the correlation of esophageal manometry and scintigraphy in Chinese was
      studied. Thirty-two volunteers (M/F: 18/14, age: 20-57) without evident
      esophageal motor disturbance and chest deformity underwent manometric measurement
      in the spine position using a low compliance pneumohydraulic infusion system.
      These measurements included the location of both upper and lower esophageal
      sphincter from nostril, and dry or wet swallow elicited peristaltic speed in the
      lower esophageal segment. Within one week after manometry, they swallowed a
      technetium-99m colloid bolus to measure radionuclide manifested esophageal
      transit time in the supine position beneath a gamma-camera. Body heights of
      enrolled subjects exhibited a significant positive correlation (r = 0.458, p <
      0.01) with manometry measured esophageal lengths. Mean radionuclide esophageal
      transit time was 7.61 +/- 2.51 sec (3.1-13.57 sec). These transit times exhibited
      a positive correlation with esophageal lengths (r = 0.6, p < 0.001). Radionuclide
      transit speed was actually slower than either dry swallow or wet swallow elicited
      speed (p < 0.05). In conclusion, either manometry or scintigraphy manifests their
      specific benefits to diagnose esophageal motility disorders. Some correlations of
      measured variables can be obtained if they are simultaneously employed.

PMID- 8549236
TI  - CO2 chemosensitivity during immersion in humans.
AB  - Hypercapnic ventilatory response was compared in 9 seated subjects during head
      out immersion in 35 degrees C (thermoneutral) water and during non-immersion in
      28 degrees C (thermoneutral) room air. Using Read's CO2-rebreathing technique,
      minute ventilation (VE) and end-tidal (ET) PCO2 were sampled continuously for 4-5
      min with a spirometer and a mass spectrometer, while the subject rebreathed a 6 L
      gas mixture initially containing 7% CO2 and 93% O2 in a bag-in-box system. The
      slope of the hypercapnic ventilatory response curve, expressed as delta VE/delta
      PETCO2, ranged from 0.76 to 2.49 L/min/mmHg. Immersion affected neither the slope
      nor the position of the hypercapnic ventilatory response curve. The rate of rise
      of PETCO2 during immersed CO2-rebreathing was significantly reduced (4.47 +/-
      0.19 [SE] mmHg/min), as compared to the control value (5.67 +/- 0.24). It was
      concluded that the CO2 chemosensitivity during immersion in humans did not change
      and that the capacity to store CO2 in tissue might have been increased.

PMID- 8549237
TI  - Special issue: Proceedings of the 188th meeting of the Netherlands
      Ophthalmological Society. The Hague, 16-18 March 1994.

PMID- 8549238
TI  - Punctal and canalicular stenosis associated with systemic fluorouracil therapy.
      Report of five cases and review of the literature.
AB  - Ocular side effects of systemic fluorouracil include excessive lacrimation, due
      to punctal and canalicular stenosis and fibrosis. Obstruction of the tear ducts
      after systemic therapy with fluorouracil is more frequent than is assumed. Five
      patients with breast cancer and punctal or canalicular stenosis are presented.
      Although complaints of epiphora usually resolve two weeks after cessation of
      systemic therapy, local antibiotics and steroids may be indicated. In patients
      with persisting complaints, and patients treated with fluorouracil for a
      prolonged period of time, prophylactic intubation of the tear ducts with silastic
      tubes has been advocated. (Conjunctivo)dacryocystorhinostomy may be unavoidable.

PMID- 8549240
TI  - Recurrent herpetic keratitis in penetrating keratoplasty.
AB  - In a retrospective study we evaluated 49 consecutive penetrating keratoplasties
      for herpes simplex keratitis. Mean follow-up was 44.2 months. Survival analysis
      with Kaplan-Meier curve showed an overall survival rate (clear graft) of 88% at
      one year, 76% at two years and 72% at four years postoperatively. Survival
      analysis showed a recurrence-free survival rate of 72% at one year, 59% at two
      years and 51% at four years postoperatively. Of the 13 non-primary graft
      failures, 9 happened in eyes with an HSV recurrence. Recurrence of HSV infection
      occurred in 18 (39%) eyes at an average of 12.6 months after surgery (range 0.3
      46). Five (28%) of the recurrences occurred within two months after the start of
      steroid treatment for rejection. Nine (50%) of the recurrences cases resulted in
      a clouded graft at the end of follow-up. 73% of the eyes with a clear graft had a
      VA of 0.25 or better. We conclude from these data that a recurrence of a herpetic
      infection following corneal transplantation is the main reason for graft failure
      in this group.

PMID- 8549239
TI  - Morphometric analysis of the corneal endothelium with three different specular
      microscopes.
AB  - The morphometry of the central corneal endothelium of 10 eyes in 10 subjects was
      analyzed with three different specular microscopes. Computer-assisted analysis
      was performed with only two microscopes (Zeiss and Keeler Konan sp 3300) because
      the third microscope (Topcon sp 1000) could not be adapted to our computerized
      system. With this Topcon microscope a grid with standard densities was used to
      compare the images with, in addition, we also performed manual cell counting on
      the same Topcon images. The coefficient of variation of the cell analysis of
      three different images per cornea with the four methods varied between 3.4 and
      4.7 percent. One-way analysis of variance showed a significant difference between
      the Zeiss and the other microscopes. So only the Keeler Konan and the Topcon
      microscopes could be used interchangeably. The computerized image analysis
      permitted also an evaluation of the hexagonality. The results of polygonality
      were not significantly different between the Zeiss and the Keeler Konan. For
      clinical purposes the Topcon specular microscope is more advantageous than the
      other two methods, since it is the most rapid way to record and analyze specular
      images. But for more precise measurements an image processing system is
      indispensable.

PMID- 8549241
TI  - Stray light in photorefractive keratectomy for myopia.
AB  - We performed a study to evaluate the influence on visual function of intraocular
      straylight after photorefractive keratectomy (PRK). We present 4 eyes of 4 myopic
      individuals, who had contacted our clinic for keratorefractive surgical
      treatment. PRK's were performed with a Summit laser, using a 5 mm ablation zone.
      The straylight meter was used to measure the amount of intraocular scattered
      light, the physical cause of glare complaints, before and after PRK. This
      apparatus uses the direct compensation method to assess the amount of intraocular
      light scatter. The results showed a significant increase in straylight values, in
      the tested eyes, during the first two weeks after PRK. After the initial rise,
      straylight values returned to preoperative levels, except for two eyes that
      clearly developed a haze higher than grade two. Instead of returning to baseline
      levels, straylight values remained significantly higher in these eyes.

PMID- 8549242
TI  - Conventional diagnostic ultrasound of iris lesions.
AB  - Eighty patients, referred for further evaluation of prominent iris lesions, were
      examined with conventional B-mode ultrasound equipment combined with a simplified
      immersion technique. The axial resolution of this system is about 350 microns. In
      20.3% of the cases, the lesion was too small for ultrasound detection. A cystic
      lesion was diagnosed in 26% and a solid lesion in 53.7% of the patients studied.
      In 33.4% of the cases, the lesions were not confined to the iris but also
      appeared in the ciliary body. This last result shows the diagnostic value of the
      conventional ultrasound examination in the evaluation apparent iris lesions.

PMID- 8549243
TI  - Astigmatism and visual recovery after phacoemulsification and conventional
      extracapsular cataract extraction.
AB  - In this study we wanted to investigate the post-operative astigmatism and visual
      acuity after phacoemulsification and conventional extracapsular cataract surgery.
      Patients operated between April and June 1993 (n = 150) were retrospectively
      analyzed. The patients were examined prior to surgery and at day 1, at day 10,
      and in week 6 post-operatively. The difference between the post-operative log
      mean visual acuity in the Phaco group and in the CECCE group was significant
      after 1 and 10 days, however it was not significant (p = 0.191) after 6 weeks.
      The mean astigmatism was significantly less in the Phaco group than in the CECCE
      group during the whole post-operative check-up period. This study suggests that
      Phaco results in a lower post-operative astigmatism and an earlier visual
      rehabilitation compared to the CECCE technique.

PMID- 8549244
TI  - Measurement of visual acuity with two different charts; a comparison of results
      and repeatability in patients with cataract.
AB  - PURPOSE: To compare two different optotypes to measure visual acuity. METHODS:
      Experiment 1: Fifty patients with moderate cataracts were asked to read a chart
      consisting of letters of the alphabet (Sloan letters) first and a chart
      comprising Landolt's broken rings afterwards. Experiment 2: Half of patients were
      instructed to repeat the reading with a second letter chart, the other half was
      instructed to read the chart with the broken rings again. RESULTS AND
      CONCLUSIONS: Experiment 1: It was found that with the letter chart more optotypes
      (two to four) were recognized than with the broken ring chart. The different
      result of visual acuity measurement with the two optotypes is irrespective of the
      visual acuity. Experiment 2: The re-read instruction revealed that the
      measurements were reproduced equally for both charts.

PMID- 8549245
TI  - Radiation therapy for age-related subfoveal choroidal neovascular membranes. A
      pilot study.
AB  - In this pilot study the effect of radiation therapy on subfoveal CNV membranes
      associated with age-related macular degeneration was evaluated. Four groups of 10
      patients were treated with external beam radiotherapy (16 MV photons) on an area
      of 1 cm2 (macular region) using a lens-sparing technique and total dose of 8 to
      24 Gy. The first group received 8 Gy in a single fraction. In this group only 30%
      had a stable visual acuity and a stable FA after 18 months follow-up. In 50% of
      patients in group 2 (12 Gy) and 40% of patients in group 3 (18 Gy) the visual
      acuity and FA appearance remained stable after 18 months of follow-up. In the
      last group (24 Gy) 80% of patients had a stable visual acuity and FA appearance
      after 12 months follow-up. Comparison of these findings with the natural history
      data of subfoveal age-related CNV, suggests a beneficial effect of radiation
      therapy with a total dose of 12 Gy or more on the progression of CNV membranes.

PMID- 8549246
TI  - Toxic keratopathy due to the accidental use of chlorhexidine, cetrimide and
      cialit.
AB  - Due to economical reasons some ophthalmologists are using an irrigating solution
      made by the hospital pharmacy instead of the commercially available solutions.
      These irrigating solutions come in bottles which are identical to the ones used
      for other solutions. During the last three years bottles were accidentally mixed
      up five times. Consequently, bottles containing solutions such as chlorhexidine,
      cetrimide, chlorhexidine/centrimide and cialit solutions were used during
      cataract surgery. This resulted in immediate corneal edema which, in its turn
      resulted in a bullous keratopathy. Four patients underwent a penetrating
      keratoplasty. In one patient the cornea was covered with a conjunctival flap.
      Light microscopy of the corneas included epithelial edema, loss of keratocytes,
      and a disrupted and sometimes absent endothelial cell layer.

PMID- 8549247
TI  - Vitreous findings in a patient with Terson's syndrome.
AB  - In Terson's syndrome a sudden increase in intracranial pressure due to
      spontaneous subarachnoid hemorrhage or head trauma may result in intraocular
      hemorrhage. A patient with bilateral vitreous hemorrhages underwent vitrectomy in
      both eyes with excellent result. In the right eye a glistening membrane was found
      with blood underneath, covering the macula. This was probably the internal
      limiting membrane (ILM). At the vitreous base and in the equatorial zone,
      attachment plaques are present between the ILM and the Muller cells. Because
      attachment plaques are missing in the posterior zone, where the ILM is much
      thicker, a retinal hemorrhage is capable of detaching the ILM from the retina in
      that area. The presence of attachment plaques is considered in relation to
      centripetal vitreous traction, which is absent in the area of the posterior
      precortical vitreous pocket (PPVP). The posterior wall of the PPVP coincides
      therefore probably exactly with the thick part of the ILM in the posterior zone.

PMID- 8549248
TI  - A special photo-epithesis. Case report.
AB  - We designed and fabricated a photo-epithesis constructed on a spectacle-frame for
      a patient who could no longer wear his prosthesis, because of severe socket
      contraction and in whom secondary reconstruction was not possible.

PMID- 8549249
TI  - Ophthalmologic abnormalities in encephalocraniocutaneous lipomatosis.
AB  - Encephalocraniocutaneous lipomatosis (ECCL) is a sporadically occurring disorder
      that belongs to the group of neurocutaneous syndromes. Important characteristics
      of the case we present are: intracranial lipomas, a skull hamartoma, bilateral
      lipodermoids and jaw tumors (ossifying fibromas and compound odontomas). We
      propose four minimal criteria for the diagnosis of ECCL and review the ocular
      abnormalities reported to date.

PMID- 8549250
TI  - 'When is VISION asked too much'?
AB  - The last two decades a shift took place from substitutional/compensatory training
      to utilisation of residual vision regarding rehabilitation of the visually
      impaired. Some of the visually impaired are able to use their visual perception
      nearly as complete as normal seeing people in spite of a severe visual
      disability. On the other hand, people with nearly normal functions can be
      severely visually handicapped. To illustrate this, two cases are presented. The
      first case is a man, aged 47 years, with a juvenile macular degeneration on both
      eyes. In spite of a very low visual acuity of less then 0.05, he finished an
      university education and he is able to maintain himself very well in a leading
      position in a scientific environment, by using adequate low vision devices. Also
      for his leisure activities, as photography and speed skating, he relies upon
      visual perception. The second case is a woman, aged 30 years, with nearly normal
      visual functions, who is not able to read for longer periods caused by
      conflicting information from the body- and eye movements, and the visual input.
      This causes sickness during reading. She is unable to use books for her study and
      is working with recordings on tape. The results of a comprehensive visual
      assessment will be related to the specific low vision devices and its use.

PMID- 8549251
TI  - Making research happen.

PMID- 8549252
TI  - From the president: collaboration in change.

PMID- 8549253
TI  - Metformin: a biguanide.
AB  - Metformin is an effective agent in the oral treatment of non-insulin-dependent
      diabetes mellitus and does not cause hypoglycemia like the sulfonylureas. This
      drug is safe provided the cautions and contraindications are followed and the
      patient is monitored for hepatic and renal function. Metformin is used
      extensively outside the United States in the treatment of type II diabetes and
      recently was approved by the FDA for marketing under the brand name of
      Glucophage.

PMID- 8549254
TI  - Teaching component skills for diabetes management to a low-functioning child.

PMID- 8549255
TI  - Gender differences in diabetes attitudes and adherence.
AB  - This study focused on three questions: Is there a difference in men's and women's
      diabetes attitudes? Do health professionals give different recommendations to men
      and women? Is there a difference between men and women in care adherence? A total
      of 1201 patients with diabetes were surveyed; 65% of these patients were women.
      Differences in diabetes attitudes (three of seven attitudes) were most evident
      between men and women with insulin-dependent diabetes mellitus (IDDM). No
      differences were found in the attitudes of men and women with non-insulin
      dependent diabetes mellitus (NIDDM) using insulin, and only one attitude was
      different for patients with NIDDM not using insulin. Few differences were
      observed in the recommendations given by health professionals to men and women.
      Gender differences in adherence to the components of self-care also were minimal.
      These findings may indicate that there are many similarities in the reactions of
      men and women who have been diagnosed with diabetes.

PMID- 8549256
TI  - Grief among parents of children with diabetes.
AB  - The observation that parents respond with grief when their children are diagnosed
      with diabetes is supported in the medical literature. Dysfunctional family
      dynamics that disrupt the process of adapting to a diagnosis of diabetes can be
      attributed to unresolved grief. Group work is advocated as an effective means of
      promoting healthy familial interactions and adjusting to life with diabetes.

PMID- 8549257
TI  - Attitudes and beliefs about exercise among persons with non-insulin-dependent
      diabetes.
AB  - This study examined attitudes and beliefs about exercise among 83 persons with
      non-insulin-dependent diabetes who had completed outpatient diabetes counseling.
      An adaptation of the Health Belief Model, labeled the Exercise Behavior Model,
      guided perceptual measures. Fifty-two percent of the subjects were exercising 3
      or more days per week. Those with a greater length of time since diabetes
      counseling were more likely to be currently exercising. Positive and negative
      attitudes toward exercise characterized the group; however, only negative
      attitudes were related to exercise. Both exercisers and nonexercisers perceived
      barriers to exercise. Other people, chance happenings, physical discomfort, and
      perceptions of fitness, weight, and appearance played a role in whether the
      subjects exercised. The results indicate that providing assistance in identifying
      support for exercise and overcoming perceived barriers to exercise may increase
      compliance to this important aspect of the diabetes regimen.

PMID- 8549258
TI  - The impact of an educational program on improving diabetes knowledge and changing
      behaviors of nurses in long-term care facilities.
AB  - Nursing staffs from two long-term care facilities attended a multisession
      educational program about the care of residents with diabetes (treatment group).
      A control group consisted of the nursing staffs from two other similar facilities
      who did not participate in the educational program. Both groups were given a
      knowledge pretest and posttest. A chart review also was conducted following the
      educational intervention to determine any changes in the diabetes care provided
      by the treatment group. Following the educational program, the treatment group
      had a significant increase in their mean score on the knowledge test compared
      with the control group. However, a review of the residents' charts revealed no
      significant increases in specific behaviors related to diabetes care. The
      findings suggest that, in addition to educational programs, more focused training
      concerning diabetes care is needed to improve the care of residents with diabetes
      in long-term care facilities. Implications for diabetes educators are discussed.

PMID- 8549259
TI  - Carbohydrate counting in the management of diabetes.

PMID- 8549260
TI  - [Normal values for dobutamine stress echocardiography].
AB  - Dobutamine stress echocardiography having established itself as a sensitive
      method for diagnosing coronary heart disease, even in the absence of normative
      values, the physiological haemodynamics as well as the physiological values for
      global and regional left ventricular myocardial function were measured. TEST
      PERSONS AND METHODS: 14 healthy subjects (ten men, four women; median age 25
      [range 21-32] years) underwent dobutamine stress echocardiography according to an
      internationally practised dosage steps protocol (5-40 micrograms/kg/min with
      additional 0.5 mg atropine at 40 micrograms). RESULTS: Maximal infusion rate
      achieved a serum dobutamine level of 1.67 micrograms/ml with minimal quartiles;
      it did not influence serum electrolytes (especially potassium). Heart rate
      increased from 64 to 150/min (P < 0.0001), blood pressure from 111/66 to 158/88
      mmHg (systolic: P < 0.0001; diastolic P < 0.001) and the double product of
      systolic pressure and heart rate from 6714 to 24571 (P < 0.001). While the end
      diastolic volume index decreased from 50 to 37 ml/m2 (P < 0.05), the end-systolic
      volume index fell from 20 to 7 ml/m2 (P < 0.0001). Regional wall motion analysis
      indicated an increase in left ventricular circumferential contractility with
      little scatter. CONCLUSIONS: The usual protocol for dobutamine stress
      echocardiography is a sensible one, because the haemodynamic effect occurs
      already at low dosage and can then be increased significantly with further dosage
      steps. High serum dobutamine concentrations can be achieved without
      arrhythmogenic hypokalaemia. Volume index and ejection fraction are especially
      discriminatory variables. Quantitative analysis of wall motion is justified
      because of the low scatter of values.

PMID- 8549261
TI  - [The risks of percutaneous endoscopic gastrostomy].
AB  - AIM OF STUDY: Percutaneous endoscopic gastrostomy (PEG) having established itself
      as the standard procedure and preferred method for artificial long-term
      intestinal nutrition, a retrospective study was undertaken to evaluate the
      complications and course after PEG. PATIENTS AND METHODS: 1299 patients in whom
      PEG had been performed between 1.8. 1984 and 1.8. 1993 were sent a standardised
      questionnaire, 1182 of which could be evaluated (954 males, 228 females; mean age
      56.7 [3-94] years). RESULTS: Total duration of PEG was 279830 days, with a mean
      of 216.2 days per patient. Mortality rate due to the procedure was 0.5%. Severe
      complications (peritonitis, perforation or faulty puncture) occurred in 9
      patients (0.9%). The most common relatively minor complications were peristomal
      wound infection (8.7%) and brief periods of abdominal pain (4.8%). Typical side
      effects specific to nutrition were gastrointestinal symptoms, like constipation,
      diarrhoea, meteorism, vomiting and other signs of illness (39.3%). CONCLUSION:
      Long-term intestinal nutrition via PEG is a safe, efficacious and cost-effective
      form of treatment which decreases demands on hospital care and reduces costs.

PMID- 8549262
TI  - [Recurrent bleeding from colonic varices in portal hypertension. The successful
      prevention of recurrence by the implantation of a transjugular intrahepatic stent
      shunt (TIPS)].
AB  - HISTORY AND CLINICAL FINDINGS: Sclerotherapy was performed in a 52-year-old
      patient with alcoholic liver cirrhosis (Child-Pugh stage A) for recurrent
      bleeding from oesophageal varices. Half a year later he again was admitted to
      hospital because of recurrent passage of bloody stools. The cardiovascular status
      was stable; the liver was enlarged by 15 cm in the medioclavicular line.
      INVESTIGATIONS: Endoscopy revealed several varices in the colon near the right
      flexure. One of the varices had an ulcer of 5 mm size. Duplex sonography revealed
      portal hypertension with cirrhosis of the liver and partial thrombosis of the
      main trunk of the portal vein without any sign of cavernous transformation.
      TREATMENT AND COURSE: Because of the partial portal vein thrombosis it was
      decided to insert a transjugular intrahepatic portosystemic stent shunt. This
      obviated the thrombosis and lowered the portosystemic pressure gradient by 6.8%.
      With the shunt functioning well there were no further bleedings in the subsequent
      year. CONCLUSION: The only slightly invasive TIPS implantation is an effective
      therapeutic procedure for bleeding from colon varices caused by portal
      hypertension.

PMID- 8549263
TI  - [Lacunar cerebral infarction in a young woman].
AB  - HISTORY AND FINDINGS: A 29-year-old woman was admitted to hospital with an acute
      right-sided hemiplegia and sensory disorders, as well as upper right quadrant
      anopsia. There were no other significant abnormalities. She had previously been
      healthy and was free of any predisposing risk factors for thromboembolism.
      Neurological examination elicited a homonymous right upper quadrant hemianopsia,
      dysesthesia of the right half of the face and hypesthesia and hypalgesia of the
      right side of the body. In addition there was paresis of the right arm and a
      positive right Babinski reflex. INVESTIGATIONS: There was no evidence for any
      underlying haematological, metabolic, infectious or vascular disease. Computed
      tomography of the head revealed a small hypodense area immediately adjacent to
      the posterior part of the left internal capsule, compatible with a lacunar
      infarction, a finding confirmed by magnetic resonance imaging and relating to the
      area supplied by the thalamic branch of the posterior cerebral artery.
      Transoesophageal echocardiography demonstrated a patent foramen ovale. TREATMENT
      AND COURSE: Almost complete regression of all signs occurred within two months on
      anticoagulation with heparin intravenously for two weeks followed by oral
      phenprocoumon (Quick's value 30-40%) and intensive physiotherapy. Five weeks
      after onset of treatment the paresis was obviously regressing and pyramidal tract
      signs had disappeared. Sensitivity to touch over the right half of the body was
      still diminished and the homonymous paracentral scotoma still present.
      CONCLUSION: Lacunar infarction of the brain in young patients has an excellent
      prognosis, as long as it is treated intensively according to its cause.

PMID- 8549264
TI  - [Cytomegalovirus disease in the AIDS patient. The current status of therapy and
      the outlook].

PMID- 8549265
TI  - [Methods in medicine: positron-emission tomography].

PMID- 8549266
TI  - [Chronic transplant damages: unsatisfactory long-term results of organ
      transplantation].

PMID- 8549267
TI  - [The 1995 Nobel Prize for medicine].

PMID- 8549268
TI  - [The therapy of toxic pulmonary edema].

PMID- 8549269
TI  - [Diuretic abuse].

PMID- 8549270
TI  - [Hazards due to antithrombosis stockings].

PMID- 8549271
TI  - [Methotrexate and misoprostol for drug-induced abortion in the first trimester].

PMID- 8549272
TI  - [The decreasing HIV-1 seroprevalence in young adults in a rural region of
      Uganda].

PMID- 8549273
TI  - [Body weight and mortality in women].

PMID- 8549274
TI  - Proceedings of the 5th International Symposium on New Quinolones. Singapore,
      August 25-27, 1994.

PMID- 8549275
TI  - Quo vadis with bacterial resistance?

PMID- 8549276
TI  - Quinolone mode of action.
AB  - Physical studies have further defined interactions of quinolones with their
      principal target, DNA gyrase. The binding of quinolones to the DNA gyrase-DNA
      complex suggests 2 possible binding sites of differing affinities. Mutations in
      either the gyrase A gene (gyrA) or the gyrase B gene (gyrB) that affect quinolone
      susceptibility also affect drug binding, with resistance mutations causing
      decreased binding and hypersusceptibility mutations causing increased binding.
      Combinations of mutations in both GyrA and GyrB have further demonstrated the
      contribution of both subunits to the quinolone sensitivity of intact bacteria and
      purified DNA gyrase. A working model postulates initial binding of quinolones to
      proximate sites on GyrA and GyrB. This initial binding then produces
      conformational changes that expose additional binding sites, possibly involving
      DNA. Quinolones also inhibit the activities of Escherichia coli topoisomerase IV
      (encoded by the parC and parE genes), but at concentrations higher than those
      inhibiting DNA gyrase. The patterns of resistance mutations in gryA and parC
      suggest that topoisomerase IV may be a secondary drug target in E. coli and
      Neisseria gonorrhoeae. In contrast, in Staphylococcus aureus these patterns
      suggest that topoisomerase IV may be a primary target of quinolone action.
      Regulation of expression of membrane efflux transporters may contribute to
      quinolone susceptibility in both Gram-positive and Gram-negative bacteria. The
      substrate profile of the NorA efflux transporter of S. aureus correlates with the
      extent to which the activity of quinolone substrates is affected by
      overexpression of NorA. In addition, the Emr transporter of E. coli affects
      susceptibility to nalidixic acid, and the MexAB OprK transport system of
      Pseudomonas aeruginosa affects susceptibility to ciprofloxacin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8549278
TI  - Quinolones in the elderly.
AB  - Aging results in a number of physiological changes that can affect drug
      disposition; these include reduced gastric acidity, decreased intestinal
      motility, lower lean body mass, and reduction in renal function. The age-related
      decline in renal function is the most important of these factors when
      administering quinolones to elderly patients. Elimination half-life (t1/2) values
      are prolonged in proportion to the degree to which the compound is normally
      eliminated by the renal route. Thus, age-related increases in t1/2 occur to a
      greater degree with ofloxacin (80 to 90% renal elimination) than with
      ciprofloxacin, which is also excreted by the gastro-intestinal route.
      Norfloxacin, pefloxacin, and sparfloxacin may also be eliminated to a substantial
      degree by the transintestinal route, as their excretion is not substantially
      affected by severe renal impairment. Prolonged drug elimination in the elderly
      can result in an increased incidence of adverse effects. Ofloxacin causes a
      higher frequency of drug-related events in the elderly, presumably reflecting the
      prolonged serum t1/2 and higher serum concentrations, and consequently higher
      tissue levels in this age group. Indeed, dosage reduction is recommended when
      treating elderly patients with ofloxacin, but does not appear necessary on the
      basis of advanced age for ciprofloxacin, norfloxacin and pefloxacin.

PMID- 8549277
TI  - Quinolones and osteomyelitis: state-of-the-art.
AB  - The present review provides a critical quantitative analysis of the use of
      quinolones in osteomyelitis. Only papers published in peer-reviewed journals and
      related to the following areas were selected: experimental osteomyelitis,
      penetration of quinolones into human bone and clinical use in comparative and non
      comparative studies. Cumulated results show clinical success rates of more than
      90% in osteomyelitis caused by Enterobacteriaceae, after prolonged oral use of
      ciprofloxacin. However, further comparative studies using oral quinolones as
      single agents or in combination (versus standard parenteral therapy) are required
      in osteomyelitis due to S. aureus or P. aeruginosa, or in more complicated
      situations such as diabetic osteomyelitis or foreign body infection.

PMID- 8549279
TI  - Quinolones in sexually transmitted diseases. Global experience.
AB  - The role of quinolones in sexually transmitted diseases is still being defined.
      In vitro and in vivo efficacy of established agents against gonorrhoea after a
      single oral dose is well established, although problems with emerging resistance
      have been identified. However, among these agents only ofloxacin is reliably
      active against Chlamydia trachomatis infection, and only as a course of
      treatment. Preliminary trials with sparfloxacin are encouraging. Other new agents
      show potentially useful in vitro activity, but clinical studies are awaited. To
      date, clinical activity of quinolones in bacterial vaginosis has been
      disappointing. The efficacy of newer agents with anaerobic activity will be of
      interest. Chancroid can be cured with ciprofloxacin or ofloxacin; resistance has
      been reported, but is not yet clinically significant. Ofloxacin appears to be
      effective therapy for pelvic inflammatory disease, without the need for
      additional anaerobe cover. The possibility of improved clinical efficacy
      justifies further in vitro and in vivo studies.

PMID- 8549280
TI  - The use of fluoroquinolones in sexually transmitted diseases in Southeast Asia.
AB  - This paper reviews the use of the fluoroquinolone antibiotics in the management
      of sexually transmitted diseases (STD) in Southeast Asia. Numerous clinical
      trials performed in the region have shown that the quinolones are highly
      effective for treating uncomplicated gonorrhoea. Norfloxacin 800 mg, ofloxacin
      400 mg, ciprofloxacin 250 mg, and pefloxacin 400 mg in single oral doses have
      yielded excellent clinical results. Overall cure rates were greater than 95%,
      with full eradication of penicillinase-producing Neisseria gonorrhoeae in all
      studies. Strains of gonococci resistant to the quinolones have already emerged
      and should be closely monitored. However, this has not become a serious problem
      to date, as large scale evaluation has shown that the quinolones remain highly
      efficacious for the treatment of gonorrhoea. These antibiotics in single doses
      are not effective for postgonococcal urethritis (PGU); therefore, concomitant use
      of an antichlamydial regimen for all patients with gonorrhoea is recommended. The
      quinolones are also highly effective for chancroid. Excellent results, with cure
      rates approaching 100%, were achieved with single oral doses of ciprofloxacin 500
      mg, norfloxacin 800 mg, and ofloxacin 400 mg. Widespread use of these drugs in
      STD treatment regimens may be one of the main factors causing a dramatic decline
      in the number of cases of chancroid seen in recent years. Ofloxacin in variable
      dosages for a period of 10 to 21 days was found to be effective in nongonococcal
      urethritis (NGU). However, when compared with the tetracyclines, it is less cost
      effective and can thus be regarded as an alternative treatment for NGU.

PMID- 8549281
TI  - Role of quinolones in the treatment of diarrhoeal diseases.
AB  - Diarrhoeal diseases are still an important health problem in both developing and
      developed countries, and resistance to commonly used antibiotics among enteric
      pathogens is a major issue. Quinolones have become important agents in the
      treatment of diarrhoeal diseases because of their excellent in vitro activity
      against pathogens and their pharmacological features. In many clinical studies,
      they appeared to be effective in the treatment of shigellosis and the prevention
      and treatment of diarrhoea in travellers. Several studies have demonstrated that
      single-dose therapy with these agents is sufficient in many cases. Their role in
      the treatment of acute salmonellosis is still controversial, because of their
      lack of efficacy in eliminating salmonella from the faeces.

PMID- 8549283
TI  - Short course quinolone therapy of typhoid fever in developing countries.
AB  - A 14-day course of chloramphenicol or cotrimoxazole has been standard
      chemotherapy for uncomplicated salmonella enteric fever for several decades. The
      new fluoroquinolones show in vitro minimum inhibitory concentrations against
      Salmonella spp. ranging from 0.003 to 0.25 mg/L. Early clinical trials with 14
      day courses of ciprofloxacin, ofloxacin or pefloxacin given orally achieved cure
      rates of 100%. Subsequent trials with 7- to 10-day courses of these
      fluoroquinolones also consistently yielded cure rates of 100%, whereas more
      recent trials of 3- to 6-day courses reported preliminary cure rates of 67 to
      99%. At present, it appears that fluoroquinolone therapy for at least 7 days is a
      cost-effective substitute for the standard drugs in uncomplicated salmonella
      infections resistant to cotrimoxazole and/or chloramphenicol. The use of shorter
      3- to 6-day courses of fluoroquinolone therapy needs further study, in view of
      lower cure rates reported in preliminary clinical trials.

PMID- 8549282
TI  - The new quinolones in the treatment of diarrhoea and typhoid fever.
AB  - Diarrhoea and typhoid fever are two important diseases in the developing world,
      particularly the Asian countries. The management of these conditions is becoming
      increasingly difficult in the face of emerging pathogen resistance. The new
      fluoroquinolones demonstrate good in vitro activity against the causative
      pathogens involved, including those that are multidrug resistant. These agents
      have been shown to be very effective in the treatment of diarrhoea and typhoid in
      clinical trials, achieving results equal to, or better than, standard drugs.
      Importantly, fluoroquinolones also considerably shorten the duration of illness,
      thereby offering rapid relief to the patient.

PMID- 8549284
TI  - The use of quinolones as therapy in granulocytopenic cancer patients. Comparison
      with other antimicrobials.
AB  - Quinolones are valuable antimicrobial agents for prevention and therapy of
      febrile neutropenia. However, as with other groups of antibacterials, there are
      limitations to the use of quinolones in immunocompromised hosts: they should not
      be used in those neutropenic patients receiving ciprofloxacin or ofloxacin for
      prophylaxis, because of the risk of infection with resistant Gram-negative, or
      less susceptible Gram-positive, organisms. There are also insufficient data to
      support monotherapy of febrile neutropenia with quinolones, although some studies
      using higher ciprofloxacin dosages have reported encouraging results. More data
      on this issue, including use in paediatric cancer patients, are required.
      Quinolones are indicated for empirical therapy in combination with agents active
      against Gram-positive organisms, such as broad spectrum penicillins with or
      without beta-lactamase inhibitors, or in combination with vancomycin or
      teicoplanin. Some studies have shown that a combination of cefotaxime or
      ceftriaxone may provide better coverage against streptococci, but there are
      insufficient data on the combination of quinolones with third generation
      cephalosporins. A specific group of patients with low risk mild to moderate
      neutropenia with solid tumours may benefit from oral therapy with quinolones in
      combination with either an aminopenicillin with a beta-lactamase inhibitor or
      clindamycin. After 10 years of quinolone use in febrile neutropenia, these agents
      can still be regarded as valuable drugs of choice; however, the incidence of
      resistance among staphylococci and Pseudomonas spp., especially in centres using
      quinolones as prophylaxis, is increasing.

PMID- 8549285
TI  - The role of new quinolones in the treatment of respiratory tract infections.
AB  - Infections of the respiratory tract are the leading cause of antibacterial
      prescribing in both hospital and community practice. The microbial aetiology is
      diverse in both of these settings and differs in the distribution and virulence
      of the pathogens. Furthermore, in recent years the antibacterial susceptibility
      of many of the common pathogens has changed significantly. In particular,
      penicillin resistance has emerged among pneumococci, while beta-lactamase
      production among Haemophilus influenzae and many Gram-negative bacilli has led to
      alterations in first-line therapy options. The fluoroquinolone antibacterials
      have been used in selected respiratory tract infections, but concerns have
      remained with regard to their efficacy in infections caused by marginally
      susceptible organisms, and in particular pneumococcal infections. The
      availability of a number of quinolones with enhanced Gram-positive activity,
      which includes Streptococcus pneumoniae, is of considerable interest. In vitro
      data and preliminary clinical experience with sparfloxacin suggest that managing
      pneumococcal lung disease with this and future agents is a distinct possibility.
      One caveat must be considered, and that is the potential for more resistant
      strains of pneumococci emerging, against which even these new quinolones could
      prove less effective.

PMID- 8549286
TI  - Veterinary use of new quinolones in Japan.
AB  - Five new quinolones are used as veterinary medicines in Japan. Benofloxacin and
      ofloxacin are orally given in feed or in drinking water for respiratory diseases
      due to Mycoplasma spp. and Escherichia coli in poultry. Enrofloxacin is
      subcutaneously, intramuscularly or orally administered to cattle and swine for
      pneumonia due to Pasteurella spp., Mycoplasma spp. and Actinobacillus
      pleuropneumoniae and diarrhoea due to E. coli, and is used orally for respiratory
      diseases in poultry. Danofloxacin is similar to enrofloxacin except that the
      former is not approved for diarrhoea in cattle and swine. Orbifloxacin is given
      intramuscularly for pneumonia and diarrhoea in cattle and swine but not for
      poultry diseases. They are effective and safe in animals, and disappear from
      edible tissues after appropriate drug withdrawal times. The quinolones are
      indicated only when first-choice drugs are ineffective, only under the direction
      of veterinarians and only for periods of less than 5 days. Under these
      conditions, it appears unlikely that quinolone use in veterinary practice will be
      detrimental to human chemotherapy.

PMID- 8549287
TI  - Fluoroquinolone toxicities. An update.
AB  - The main types of adverse effects associated with quinolones are uncommon and
      reversible and vary in frequency among different agents. Phototoxicity appears
      more frequent with lomefloxacin than with some other quinolones. Three mechanisms
      have been proposed to explain the neurotoxic effects, including rare
      proconvulsant activity, associated with quinolone therapy. Arthropathy remains a
      dilemma for paediatricians deciding whether to use quinolones in growing
      children. Importantly, the experience with temafloxacin, which has now been
      withdrawn from the market, emphasises the need for thorough postmarketing
      surveillance. Nonetheless, it should be remembered that the fluoroquinolones as a
      group are effective and very well tolerated antimicrobial drugs.

PMID- 8549288
TI  - Classification and structure-activity relationships of fluoroquinolones.
AB  - Fluoroquinolones are potent broad spectrum antibacterial agents. Two
      classifications have been described: chemical and biological. Quinolones can be
      classified into 4 groups according to their chemical structures: monocyclic,
      bicyclic, tricyclic and tetracyclic derivatives. Each group can be subdivided
      into subgroups if a fluorine atom is fixed at the 6-position. The biological
      classification recognised 4 groups. Groups 1 and 2 are composed of compounds
      showing limited spectra (Enterobacteriaceae) and groups 3 and 4 contain compounds
      displaying broad antibacterial spectra. Compounds that are highly metabolised
      fall into groups 1 and 3 and those poorly metabolised (< 5%) into groups 2 and 4.
      The structure of fluoroquinolones may help to predict antibacterial activity,
      pharmacokinetics, physicochemical properties, toxicity and adverse events.

PMID- 8549289
TI  - Direct analysis of resistance in the cutaneous microflora during treatment of
      acne vulgaris with topical 1% nadifloxacin and 2% erythromycin.

PMID- 8549291
TI  - The susceptibility of Mycobacterium tuberculosis and atypical mycobacteria in
      northern Israel.

PMID- 8549292
TI  - Changes in susceptibility to ciprofloxacin in a community in northern Israel.

PMID- 8549290
TI  - Quinolone susceptibility of multiply-resistant Flavobacterium meningosepticum
      clinical isolates in one urban hospital.

PMID- 8549293
TI  - Ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa from
      Italian patients.

PMID- 8549294
TI  - Susceptibility to new quinolones of Pseudomonas aeruginosa isolated from a
      patient with chronic respiratory tract infection.

PMID- 8549295
TI  - Resistance among important pathogens and the antimicrobial activity of parenteral
      fluoroquinolones at 43 US medical centres.

PMID- 8549296
TI  - Analysis of quinolone resistance genes in a clinical isolate of quinolone
      resistant MRSA.

PMID- 8549297
TI  - Effect of quinolone use on antimicrobial susceptibility patterns over a 5-year
      period.

PMID- 8549298
TI  - Fluoroquinolone resistance patterns after formulary addition of ofloxacin. A
      clinical isolate study.

PMID- 8549299
TI  - Quinolone resistance mechanisms in Klebsiella pneumoniae.

PMID- 8549300
TI  - Uptake of ciprofloxacin in methicillin-resistant Staphylococcus aureus.

PMID- 8549301
TI  - Activities of ciprofloxacin and sparfloxacin against Streptococcus pneumoniae.

PMID- 8549302
TI  - Pharmacodynamics of quinolones.

PMID- 8549303
TI  - In vitro susceptibility to ciprofloxacin of bacterial strains isolated from
      chronic otitis media and chronic sinusitis.

PMID- 8549305
TI  - In vitro antimicrobial activity of CP-99,219, a new 7-azabicyclonaphthyridone.

PMID- 8549304
TI  - Comparative in vitro activity of ciprofloxacin vs 8 antimicrobial agents against
      nosocomial multiresistant P. aeruginosa strains.

PMID- 8549306
TI  - Evaluation of the anti-rickettsial activity of fluoroquinolones.

PMID- 8549307
TI  - Activity of levofloxacin, ofloxacin, D-ofloxacin and ciprofloxacin against
      systemic and respiratory tract infections in laboratory animals.

PMID- 8549308
TI  - Susceptibility of bacterial isolates from complicated skin and skin structure
      infections to cefazolin, imipenem-cilastatin, ciprofloxacin and ofloxacin.

PMID- 8549309
TI  - In vitro and in vivo antibacterial activities of broad spectrum quinolones
      against clinical bacterial isolates.

PMID- 8549310
TI  - Comparative in vitro activity of BAY Y 3118 with other fluoroquinolones.

PMID- 8549311
TI  - Activity of new 4-quinolones in combination with erythromycin or tetracycline
      against S. pneumoniae.

PMID- 8549312
TI  - The new 4-quinolones DU-6859a and DV-7751a show enhanced activity against
      Streptococcus pneumoniae.

PMID- 8549313
TI  - In vitro activity of nadifloxacin against both methicillin-susceptible and 
      resistant clinical isolates of Staphylococcus aureus from patients with skin
      infections.

PMID- 8549314
TI  - In vitro activity of new quinolones against anaerobic bacteria.

PMID- 8549315
TI  - Activity of DU-6859a, ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and
      OPC-17116 against 112 penicillin-susceptible and -resistant pneumococci.

PMID- 8549316
TI  - The antimicrobial activity of sparfloxacin, a new quinolone.

PMID- 8549317
TI  - In vitro and in vivo antibacterial activities of CFC-222, a novel broad spectrum
      fluoroquinolone.

PMID- 8549318
TI  - In vitro susceptibility of mycoplasmas to a new quinolone, BAY Y 3118.

PMID- 8549319
TI  - In vitro activity of ofloxacin, ciprofloxacin, and cefoperazone alone and in
      combination against Xanthomonas maltophilia.

PMID- 8549320
TI  - In vitro and in vivo activities of sparfloxacin in Legionella infections.

PMID- 8549322
TI  - In vitro activity of sparfloxacin against selected gram-negative blood culture
      isolates.

PMID- 8549321
TI  - Study of the effects of AM-1155 in a rat chronic respiratory tract infection
      model with Pseudomonas aeruginosa.

PMID- 8549323
TI  - Antichlamydial activities of newly developed fluoroquinolones and their potential
      future role in the treatment of chlamydial respiratory infections.

PMID- 8549324
TI  - In vitro activity of tosufloxacin against Pseudomonas pseudomallei, Salmonella
      spp. and other Enterobacteriaceae.

PMID- 8549325
TI  - Evaluation of the activity of different quinolones in the experimental chlamydial
      salpingitis mouse model.

PMID- 8549326
TI  - Comparative in vitro activity of BAY Y 3118 against selected species.

PMID- 8549327
TI  - Antimicrobial evaluation of nadifloxacin (OPC-7251), a new topical quinolone, in
      acne vulgaris.

PMID- 8549328
TI  - Comparison of the pharmacodynamic properties of quinolones.

PMID- 8549329
TI  - In vitro activity of MF 5137, a new potent 6-aminoquinolone.

PMID- 8549330
TI  - In vitro antibacterial activity of levofloxacin.

PMID- 8549331
TI  - Effect of subinhibitory concentrations of pefloxacin in infection in mice due to
      susceptible or resistant strains.

PMID- 8549333
TI  - Evaluation of photosensitising ability of quinolones in guinea-pigs.

PMID- 8549332
TI  - Expression of beta 1-integrins on epiphyseal chondrocytes is reduced by
      ofloxacin.

PMID- 8549334
TI  - Effect of inhibitors of protein kinase C on enhanced superoxide production of
      human leucocytes by ofloxacin and fleroxacin.

PMID- 8549335
TI  - Restorative effect of ofloxacin on inhibited chemiluminescence response of PMNs
      by sera from uraemic patients.

PMID- 8549336
TI  - Mechanisms of resistance to fluoroquinolones: state-of-the-art 1992-1994.
AB  - This paper gives an update on the mechanisms of bacterial resistance to
      fluoroquinolones. The laboratory techniques currently used to determine the
      mechanism(s) of resistance are outlined, including the use of restriction
      fragment length polymorphism and single-stranded conformational polymorphism
      analysis of mutations in gyrA. Alterations in gyrA have continued to be the most
      reported cause of resistance, with high level resistance due to 2 or more
      mutations in this gene. Recently, mutations in gyrA of Mycobacterium tuberculosis
      and Campylobacter jejuni have been described. Complementation studies with
      plasmid encoded cloned gyrB from Escherichia coli suggest that high
      fluoroquinolone resistance (minimum inhibitory concentration = 32 mg/L) in
      Salmonella typhimurium can be due to mutation in both gyrA and gyrB. Decreased
      fluoroquinolone accumulation into E. coli has been shown to be due to mutations
      in a number of genes at different loci. Current interest has focused upon the
      marRAB and soxRS loci, with mutations in genes of either loci giving rise to
      decreased susceptibility to several unrelated drugs, including fluoroquinolones,
      tetracycline, chloramphenicol and some beta-lactams, and decreased expression of
      OmpF. The genetic characterisation of fluoroquinolone efflux from Staphylococcus
      aureus has shown that efflux occurs in both fluoroquinolone-susceptible and 
      resistant bacteria. The most likely cause of resistance is overexpression of
      NorA, giving rise to increased efflux. Recently, 2 efflux systems in Pseudomonas
      aeruginosa have been proposed, MexA-MexB-OprK and MexC-MexD-OprM, conferring
      decreased susceptibility to fluoroquinolones, tetracycline, chloramphenicol and
      some beta-lactams.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549338
TI  - Ofloxacin alters expression of integrins on chondrocytes from mouse fetuses in
      vitro.

PMID- 8549337
TI  - Absence of neuromuscular blocking activity of sparfloxacin.

PMID- 8549339
TI  - In vitro effect of ciprofloxacin and ofloxacin on murine and human colon
      carcinoma cell lines.

PMID- 8549340
TI  - Effect of ciprofloxacin on cholinergic neuro-effector transmission in airway
      smooth muscle.

PMID- 8549341
TI  - Effect of ciprofloxacin and other quinolones on granulocyte function assessed by
      flow cytometry.

PMID- 8549342
TI  - Release of pefloxacin bonded on catheters after intraperitoneal implantation in
      mice.

PMID- 8549343
TI  - Sparfloxacin secretion across Caco-2 cells involves a multidrug resistance-like
      mechanism.

PMID- 8549344
TI  - Comparison of models for studying the intestinal elimination of ciprofloxacin in
      the rat.

PMID- 8549345
TI  - Pharmacokinetics of ofloxacin--measurement of drug concentration in saliva of
      patients with impaired renal function.

PMID- 8549346
TI  - Differences between albino and pigmented rabbit eyes in the intraocular
      pharmacokinetics of sparfloxacin.

PMID- 8549347
TI  - Comparative assessment of the pharmacokinetics and pharmacodynamics of
      ciprofloxacin after single i.v. doses of 200 and 400mg.

PMID- 8549348
TI  - Pharmacokinetics of CFC-222 in animals.

PMID- 8549349
TI  - Pharmacokinetic study of a new quinolone, DW-116.

PMID- 8549350
TI  - NM441: penetration into gynaecological tissues and in vitro activity against
      clinical isolates from obstetric and gynaecological patients.

PMID- 8549351
TI  - Excretion of new quinolones and their glucuronide conjugates into human bile.

PMID- 8549352
TI  - Stereoselectivity of ofloxacin intestinal transport in the rat.

PMID- 8549353
TI  - Pharmacokinetics of T-3761 in healthy volunteers.

PMID- 8549354
TI  - Penetration of NM441, a new quinolone, into human bile and gallbladder tissue.

PMID- 8549355
TI  - Gallbladder tissue concentrations, biliary excretion and pharmacokinetics of OPC
      17116.

PMID- 8549356
TI  - The pharmacokinetics and distribution of ofloxacin into the lower respiratory
      tract.

PMID- 8549357
TI  - The effect of milk consumption on the pharmacokinetics of fleroxacin and
      ciprofloxacin in healthy volunteers.

PMID- 8549358
TI  - Effect of fenbufen on the penetration of quinolone antibiotics into cerebrospinal
      fluid. Comparative study with 5 quinolones.

PMID- 8549359
TI  - Effect of ferrous sulfate on the absorption of sparfloxacin in healthy volunteers
      and rats.

PMID- 8549360
TI  - The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple
      dose caffeine.

PMID- 8549361
TI  - Epidemiology of quinolone resistance: Europe and North and South America.
AB  - After nearly 10 years of fluoroquinolone usage for a wide range of bacterial
      infections, a striking difference has been observed in the incidence of bacterial
      resistance to fluoroquinolones between bacteria responsible for community- and
      hospital-acquired infections, respectively. Resistance is only rarely encountered
      among common pathogens. In most studies, 97 to 100% of all pathogens are fully
      susceptible to fluoroquinolones. In contrast, resistance to fluoroquinolones has
      emerged and increased among bacteria responsible for nosocomial infections. The
      incidence of resistance to fluoroquinolones varies between bacterial species,
      clinical settings and countries, and is related to local epidemic spread of a few
      clones. The highest incidence of resistance is observed in Pseudomonas
      aeruginosa, Acinetobacter spp., Serratia marcescens and, particularly,
      methicillin-resistant Staphylococcus aureus (MRSA): some investigators have
      reported 95 to 100% fluoroquinolone resistance among MRSA. Follow-up of trends in
      the resistance to fluoroquinolones based upon surveillance programmes are needed.

PMID- 8549362
TI  - Effects of antacid on absorption and excretion of new quinolones.

PMID- 8549363
TI  - Evaluation of clinical efficacy of antimicrobials in complicated urinary tract
      infections. Comparison of Japanese criteria with IDSA guidelines. Infectious
      Diseases Society of America.

PMID- 8549364
TI  - Comparative efficacies of oral pefloxacin in uncomplicated cystitis. Single dose
      or 3-day therapy.

PMID- 8549365
TI  - A randomised controlled trial of ofloxacin 200 mg 4 times daily or twice daily vs
      ciprofloxacin 500 mg twice daily in elderly nursing home patients with
      complicated UTI.

PMID- 8549366
TI  - Effectiveness of ofloxacin therapy in preventing functional impairment and
      increased mortality in elderly patients with bacteriuria.

PMID- 8549368
TI  - Laboratory and clinical study of T-3761, a new fluoroquinolone, in urinary tract
      infection.

PMID- 8549367
TI  - Laboratory and clinical study of balofloxacin (Q-35), a new fluoroquinolone, in
      urinary tract infection.

PMID- 8549369
TI  - Clinical assessment of indices for the prognosis of urinary tract infection in
      elderly patients receiving prophylaxis with norfloxacin.

PMID- 8549370
TI  - Comparison of 2 oral ofloxacin regimens for the treatment of bacteriuria in
      elderly subjects.

PMID- 8549372
TI  - Ofloxacin. Therapeutic results in Chlamydia trachomatis genital infection.

PMID- 8549371
TI  - Efficacy and safety of single oral dose sparfloxacin vs ciprofloxacin in acute
      gonococcal urethritis in males. A multicentre international study.

PMID- 8549373
TI  - Antimicrobial activity, pharmacokinetics and clinical studies of balofloxacin (Q
      35) in obstetrics and gynaecology.

PMID- 8549374
TI  - Clinical study of T-3761 in obstetrics and gynaecology.

PMID- 8549375
TI  - Clinical experience with OPC-17116 in the treatment of gynaecological infections
      and its penetration into gynaecological tissues. Japanese Collaborative Study
      Group of OPC-17116 in Gynaecology.

PMID- 8549376
TI  - Single dose ofloxacin in the eradication of pharyngeal carriage of Neisseria
      meningitidis.

PMID- 8549377
TI  - Pharmacokinetic and clinical studies of T-3761 in otorhinolaryngeal infections.

PMID- 8549378
TI  - In vitro activity and clinical efficacy of ciprofloxacin in otorhinolaryngeal
      infections.

PMID- 8549379
TI  - Sparfloxacin empirical therapy in community-acquired pneumonia. Results of a meta
      analysis of 2 comparative studies.

PMID- 8549380
TI  - Additive effect of continuous low dose ofloxacin on erythromycin therapy for
      sinobronchial syndrome.

PMID- 8549381
TI  - Experimental and clinical studies of sparfloxacin in Mycoplasma pneumoniae
      infection.

PMID- 8549382
TI  - Inhibitory effect of ofloxacin on acute exacerbations of chronic respiratory
      tract infections in comparison with erythromycin.

PMID- 8549383
TI  - Clinical evaluation of levofloxacin 200 mg 3 times daily in the treatment of
      bacterial lower respiratory tract infections.

PMID- 8549384
TI  - Levofloxacin: penetration into sputum and once-daily treatment of respiratory
      tract infections.

PMID- 8549385
TI  - Sparfloxacin, a new generation fluoroquinolone against S. pneumoniae respiratory
      infections.

PMID- 8549386
TI  - Comparative study of efficacy and safety of ciprofloxacin and cefixime in the
      treatment of acute exacerbations of chronic bronchitis after first-line treatment
      failure. French Study Group.

PMID- 8549387
TI  - Levofloxacin in patients with severe respiratory tract infection.

PMID- 8549388
TI  - Clinical efficacy of levofloxacin in elderly patients with respiratory tract
      infections.

PMID- 8549389
TI  - Epidemiology of quinolone resistance. Eastern hemisphere.
AB  - Both nalidixic acid and fluoroquinolones are used widely in the Eastern
      hemisphere for a variety of infectious diseases. A surveillance programme for
      antibiotic resistance in common pathogens has been conducted in the Western
      Pacific Region of the World Health Organization since 1989. Data on resistance to
      fluoroquinolones for the years 1992 and 1993 from the 16 participating countries
      in the Western Pacific, plus published data from Thailand, were collated for
      common and important pathogens in this region. Overall, fluoroquinolone
      resistance levels were highest in developing countries and lowest in developed
      countries, with transitional countries undergoing rapid economic improvement
      showing intermediate levels of resistance. There was also a trend towards
      increasing levels of fluoroquinolone resistance between 1992 and 1993. In
      developed countries, levels of resistance to fluoroquinolones exceeded 10% for
      only Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter and
      Providencia species. Resistance levels of 25% or more in Escherichia coli were
      noted in 3 countries in 1993. In contrast, resistant strains of Salmonella typhi
      and S. paratyphi A were rare or nonexistent in any country, and only low levels
      of resistance were detected in Shigella species. Fluoroquinolone resistance
      appears to be emerging slowly in developed countries and more rapidly in
      transitional and developing countries. Strenuous efforts will be required in some
      countries in order to prevent the early obsolescence of these valuable agents.

PMID- 8549390
TI  - A comparative study of ofloxacin twice and three times daily in the treatment of
      respiratory tract infections.

PMID- 8549391
TI  - Oral levofloxacin 600 mg and 300 mg daily doses in difficult-to-treat respiratory
      infections.

PMID- 8549392
TI  - Comparison of ciprofloxacin with imipenem in the treatment of severe pneumonia in
      hospitalised geriatric patients.

PMID- 8549393
TI  - Treatment of severe pneumonia in hospitalised patients. Results of a multicentre
      trial comparing i.v. ciprofloxacin with imipenem/cilastatin.

PMID- 8549394
TI  - Causative organisms in acute exacerbation of chronic airways disease and response
      to ofloxacin therapy.

PMID- 8549395
TI  - Efficacy of ofloxacin in lower respiratory tract infections bacteriologically
      diagnosed by fibreoptic-bronchoscopy aspirate culture.

PMID- 8549396
TI  - Clinical efficacy of ofloxacin in acute exacerbations of chronic respiratory
      disease.

PMID- 8549397
TI  - Oral ciprofloxacin in the treatment of cholera.

PMID- 8549398
TI  - Double-blind comparison of ofloxacin for 3 days and placebo in acute bacterial
      enteritis.

PMID- 8549399
TI  - Multiply-resistant Salmonella typhi in children.

PMID- 8549400
TI  - Antimicrobial treatment of adults with cholera due to Vibrio cholerae 0139
      (synonym Bengal).

PMID- 8549401
TI  - A comparative study of short course ciprofloxacin treatment in typhoid and
      paratyphoid fever.

PMID- 8549403
TI  - Interim results from a multicentre clinical trial of T-3761 in Japan.

PMID- 8549402
TI  - Antimicrobial treatment of cholera.

PMID- 8549404
TI  - Once-daily ofloxacin for hospitalised patients with severe bacterial infections.

PMID- 8549405
TI  - Phase IV study (postmarketing surveillance) of Tarivid (ofloxacin) in China.

PMID- 8549406
TI  - Oral ciprofloxacin vs intravenous therapy with nonquinolone agents. A study of
      291 infections.

PMID- 8549407
TI  - In vitro activity of fluoroquinolones against gram-positive bacteria.
AB  - This paper reviews the in vitro activities of several newer fluoroquinolone
      antimicrobials that exhibit enhanced potency against Gram-positive bacteria.
      Several of these agents demonstrate 10-fold greater activity than older members
      of this class against Staphylococcus aureus and inhibit [minimum inhibitory
      concentration (MIC90) values < or = 2 mg/L] many isolates resistant to
      ciprofloxacin or ofloxacin. Markedly enhanced activity is also noted against
      Streptococcus pneumoniae, 90% of isolates being inhibited at concentrations 10-
      to 100-fold lower than those of the older agents. Enterococci also exhibit
      greater susceptibility to several of the newer fluoroquinolones, although
      relative cross-resistance with the earlier drugs is noted. As determined by
      dilution techniques, the new fluoroquinolones generally demonstrate bactericidal
      activity at concentrations at or near their MIC values. The activities of the new
      compounds described here are decreased at low pH, but are not affected by the
      addition of up to 50% human serum to the test medium. Resistance is rarely
      detected (frequency < 10(-9)) when high density bacterial suspensions are plated
      in the presence of 4 times the MIC of these compounds. However, colonies
      displaying relative resistance to the new agents can be selected by serial
      passage in incremental antimicrobial concentrations.

PMID- 8549408
TI  - Single dose UTI prophylaxis in transurethral surgery. Oral ofloxacin vs
      parenteral cefotaxime.

PMID- 8549409
TI  - Once-daily pefloxacin + teicoplanin vs netilmicin + teicoplanin in empirical
      therapy for fever and neutropenia.

PMID- 8549410
TI  - Ciprofloxacin in the treatment of serious infections in systemic lupus
      erythematosus.

PMID- 8549411
TI  - Initial clinical experience with clinafloxacin in the treatment of serious
      infections.

PMID- 8549412
TI  - Magnetic resonance imaging in diagnosis of potential arthropathogenicity in
      children receiving quinolones. No evidence of quinolone-induced arthropathy.

PMID- 8549413
TI  - Surveillance of adverse reactions due to ciprofloxacin in Japan.

PMID- 8549414
TI  - Safety evaluation of a new formulation of intravenous ofloxacin.

PMID- 8549415
TI  - Preference for costly fluoroquinolones by casual workers and daily wage earners
      in developing countries.

PMID- 8549416
TI  - Decreased fluoroquinolone use with a pharmacy service-pharmaceutical company
      partnership.

PMID- 8549417
TI  - Consequences of incomplete antibacterial treatment for chlamydial pelvic
      inflammatory disease.

PMID- 8549418
TI  - Activity of quinolones against gram-positive cocci: clinical features.
AB  - The potential role of the commercially available fluoroquinolones in the
      treatment of Gram-positive infections is discussed on the basis of data obtained
      from animal experiments and clinical trials. In respiratory tract infections, and
      particularly in community-acquired pneumonia, it is evident that the presently
      available quinolones cannot be prescribed empirically as first-line therapy
      because of their borderline activity against Streptococcus pneumoniae and
      anaerobes. Reports of pneumococcal seeding in other tissues during quinolone
      therapy render their administration a debatable issue. Experience in endocarditis
      is limited to the use of ciprofloxacin plus rifampicin in intravenous drug users
      with right-sided Staphylococcus aureus endocarditis. Patients with staphylococcal
      osteomyelitis are included among cases of other bone infections. In noncontrolled
      studies ciprofloxacin, ofloxacin and pefloxacin attained a staphylococcal
      eradication rate ranging from 70 to 100%, while the addition of rifampicin has
      been proven to reduce the emergence of resistant mutants during therapy. In soft
      tissue and skin structure infections that also involve Gram-negative bacteria,
      ciprofloxacin and ofloxacin eradicated 72.6 and 89% of staphylococci,
      respectively; however, the presence of diabetes or vascular disease compromised
      the success of treatment. In staphylococcal peritonitis complicating continuous
      ambulatory peritoneal dialysis, results with ciprofloxacin given intravenously or
      intraperitoneally were promising. In infections in neutropenic hosts, success of
      prophylaxis or therapy is still not clear, since colonisation and breakthrough
      bacteraemias with viridans streptococci and staphylococci have been reported.
      Furthermore, therapeutic results are compromised by the low response rate in Gram
      positive infections. Despite the reported clinical efficacy of the newer
      fluoroquinolones, physicians should be alerted to the emergence of staphylococci
      resistant to fluoroquinolones, mainly methicillin-resistant variants.

PMID- 8549419
TI  - Activity of quinolones against mycobacteria.
AB  - The fluoroquinolones have been shown to be highly active in vitro against many
      mycobacterial species, including most strains of Mycobacterium tuberculosis and
      M. fortuitum, and some strains of M. kansasii, M. avium-intracellulare (MAI)
      complex and M. leprae. Ciprofloxacin, ofloxacin and sparfloxacin are the best
      studied of this class of drugs to date, and they are among the most active of
      these against M. tuberculosis and other mycobacteria. The use of ofloxacin in the
      treatment of patients with multidrug-resistant pulmonary tuberculosis has
      resulted in the selection of quinolone-resistant mutants in a few patients. Many
      strains of MAI, however, are resistant to fluoroquinolones, and structure
      activity relationship studies have been undertaken to identify the moieties
      associated with activity and inactivity. The most important features determining
      activity against MAI were found to be a cyclopropyl ring at the N1 position,
      fluorine atoms at positions C6 and C8, and a C7 heterocyclic substituent. On the
      basis of these structural requirements, a series of compounds were tested, and
      many did indeed show good activity against MAI in vitro. Application of these
      data to macrophage and animal models is in progress. Clinical evaluation of some
      of these new fluoroquinolones is also being undertaken in multidrug-resistant
      tuberculosis and MAI and M. leprae infections. Although the development of
      resistance and the influence of host factors may limit their use, they have
      considerable potential if prudently used.

PMID- 8549420
TI  - Quinolone activity against anaerobes: microbiological aspects.
AB  - Currently available quinolones are either inactive or marginally active against
      anaerobic bacteria. This review summarises the in vitro activity of currently
      available as well as experimental quinolones against clinically significant
      anaerobic bacteria. Quinolones with low activity against anaerobes include
      ciprofloxacin, ofloxacin, levofloxacin, fleroxacin, pefloxacin, enoxacin,
      lomefloxacin and probably E 4868 and NM 441. Compounds with intermediate anaerobe
      activity include sparfloxacin, grepafloxacin, PD 131628 and AM 1155. Quinolones
      that are very active against anaerobes include clinafloxacin and DU 6859a. CP
      99,219, a naphthyridone, is also very active against anaerobes. Toxicity problems
      have necessitated the withdrawal of some quinolones shown to have intermediate
      activity (temafloxacin and tosufloxacin) and the discontinuation of the
      development of some investigational agents (Win 57273 and BAY Y 3118) with high
      activity. Conclusions regarding the therapeutic value of quinolones against human
      anaerobic infections await further clinical toxicological and pharmacokinetic
      studies.

PMID- 8549421
TI  - Effect of quinolones on the human intestinal microflora.
AB  - The quinolones exhibit a selective suppressive effect on the intestinal
      microflora. The aerobic Gram-negative bacteria are strongly suppressed, while the
      aerobic Gram-positive bacteria are less affected, with ciprofloxacin and
      ofloxacin having the greatest effect. The anaerobic microflora is not affected by
      administration of norfloxacin, but is suppressed slightly by ciprofloxacin and
      ofloxacin, and moderately by sparfloxacin and temafloxacin. Very high
      concentrations of the quinolones are obtained in faeces, far exceeding the
      minimum inhibitory concentration for most aerobic and anaerobic bacteria. The
      discrepancy between in vivo and in vitro outcome is explained by the binding of
      the quinolones to faeces, and by inoculum effects. These ecological properties of
      the quinolones on the intestinal microflora make them suitable for treatment of
      bacterial enteric infections, selective decontamination and prophylaxis against
      travellers' diarrhoea.

PMID- 8549422
TI  - Prophylactic use of the new quinolones for prevention of nosocomial infection in
      the intensive care unit.
AB  - The new quinolone antimicrobial agents, particularly those with less activity
      against anaerobes, selectively prevent colonisation of the alimentary tract by
      Gram-negative bacilli and staphylococci without substantially affecting the
      normal anaerobic flora, which preserve the colonisation resistance of the gut.
      These properties ideally position this class of antibacterial agent for selective
      decontamination of the digestive tract (SDD) in the prevention of nosocomial
      infection. The rationale for this procedure is based on the presumption that a
      significant proportion of infections in compromised patients are endogenous in
      origin, arising from the host's own microbial flora. If this colonisation by
      potentially pathogenic microflora within the normal flora can be significantly
      reduced without being replaced by other more pathogenic microorganisms, the risk
      of endogenous infection should be minimised. The quinolones have proved to be
      ideal agents for use in preventing infection in bone marrow transplant and other
      neutropenic patients. They have been used for SDD in the general intensive care
      unit population, although the technique has not received widespread acceptance.
      There have been only 4 reported randomised studies using quinolones as part of
      SDD regimens and only 301 patients have been evaluated. Although the incidence of
      ventilator-associated pneumonia has been significantly reduced from 36 to 15%, no
      effect has been shown on mortality. The cost of using SDD is significantly less
      with the quinolones than with other regimens, and induction of resistance has not
      been noted. The new quinolones, and in particular the more recently developed
      agents with extended Gram-positive activity, appear to be ideally suited for SDD,
      and their careful evaluation in further large, well designed trials is warranted.

PMID- 8549423
TI  - Fluoroquinolones in paediatrics--1995.
AB  - The fluoroquinolones are characterised by a broad spectrum of antibacterial
      activity that includes many Mycobacterium, Chlamydia, Legionella, and Mycoplasma
      species as well as many multiply-resistant bacterial strains, good oral
      bioavailability, extensive tissue penetration, low protein binding and long
      elimination half-lives. Numerous clinical trials have shown that these compounds
      are effective and well tolerated in the treatment of adult patients with various
      infections, including urinary tract, respiratory tract, skin and soft tissue,
      bone and joint, and gynaecological infections, sexually transmitted diseases,
      infectious diarrhoea, infections in immunocompromised patients, and in surgical
      prophylaxis. Thus, there is increasing pressure to use this class of drugs in
      paediatric patients. However, concerns regarding adverse effects, particularly
      cartilage toxicity, have restricted development of the fluoroquinolone compounds
      for use in this population. Potential indications include Pseudomonas infections
      (mainly exacerbations of cystic fibrosis), urinary tract, gastrointestinal and
      central nervous system infections, infections in immunocompromised patients,
      certain otorhinolaryngological infections and infections caused by multiply
      resistant pathogens. To date, clinical experience gained with fluoroquinolones in
      paediatric infections, which has been mainly on a compassionate-use basis,
      indicates that well-designed formal studies should be conducted to fully assess
      the efficacy and tolerability of these agents in specific indications in
      children.

PMID- 8549424
TI  - Transgenic systems in studying myelin gene expression.
AB  - The myelin sheath is produced by oligodendrocytes in the central nervous system
      (CNS) and Schwann cells in the peripheral nervous system (PNS). It is necessary
      to introduce DNA into these cells to study gene regulation and the functions of
      myelin proteins. Since these cells are labile to commonly used techniques to
      introduce DNA, a transgenic system must be used for these studies. Myelin basic
      protein (MBP) and myelin proteolipid protein (PLP) are both highly abundant in
      CNS myelin, but are also produced in Schwann cells. Various lengths (6.5 kb to
      256 bp) of the promoter region of the (classic) MBP gene directed oligodendrocyte
      specific expression of the reporter gene in transgenic mice, but no expression
      was seen in Schwann cells. Promoter regions of the PLP gene (4.2-2.4 kb) seem to
      contain all the information required for correct spatiotemporal expression, but
      the level of expression was low. The first intron of the PLP gene is a candidate
      for the location of the enhancer-like element. Studies on MBP mutant mice
      carrying wild-type MBP gene or cDNA clearly demonstrated that one function of MBP
      is to make myelin lamellae compact by fusing the cytoplasmic surfaces of
      oligodendrocytes into the form of major dense lines. However, functional analysis
      of PLP gene products using a similar strategy produced confusing results. The
      wild-type PLP gene introduced into jimpy mutant mice (one of the PLP mutants) did
      not complement the mutant phenotype. Moreover, overexpression of the PLP gene
      itself (in wild-type background) was shown to produce a phenotype similar to that
      of the mutants, including arrest in oligodendrocyte maturation and
      hypomyelination. Thus, PLP gene products play a fundamental role in
      oligodendrocyte maturation as well as in the stabilization of myelin structure,
      and its expression must be tightly regulated.

PMID- 8549425
TI  - Ganglioside markers GD3, GD2, and A2B5 in fetal human neurons and glial cells in
      culture.
AB  - Expression of ganglioside markers GD3, GD2, and A2B5 was investigated in primary
      cell cultures isolated from fetal human brains of 12-15 weeks' gestation by
      immunocytochemistry. None of neuron-specific enolase (NSE)+ neurons expressed
      GD3, while large numbers of NSE+ neurons expressed GD2 (72%) or A2B5 (48%). In
      GFAP+ astrocytes, GD3 was expressed in a small population (3%) with a high
      proliferative capacity. GD2 expression was observed in 20% of GFAP+ astrocytes,
      while A2B5 was identified in a very small number (2%) of GFAP+ astrocytes. GD2
      was coexpressed in a small population (11%) of GD3+ astrocytes, while A2B5 was
      colocalized in more than 50% of GD3+ astrocytes. In galactocerebroside+
      oligodendrocytes, GD3 expression was not observed but a small population (8-9%)
      expressed GD2 and A2B5. In Ricinus communis agglutinin (RCA)+ microglia, neither
      GD3, GD2, nor A2B5 were identified. Our results indicate that in fetal human
      brain cell cultures, GD3 is expressed in a small population of astrocytes, while
      both GD2 and A2B5 are expressed in a large population of neurons and smaller
      populations of astrocytes and oligodendrocytes. Our results suggest that both GD3
      and A2B5, cell type-specific markers for oligodendrocyte-type 2 astrocyte
      progenitor cells in the rat central nervous system, could not be utilized as
      valid markers for glial precursor cells in fetal human brain cell cultures.

PMID- 8549426
TI  - Development of glial cytoarchitecture in the frog spinal cord.
AB  - The origin of astrocytes and oligodendrocytes in the frog spinal cord, and the
      factors that regulate their differentiation are currently unknown. To determine
      the timing and pattern of glial cell differentiation, spinal cord sections from
      Xenopus at different developmental stages were labeled with antibodies specific
      for astrocytes and oligodendrocytes. Initially, radially oriented glial cells are
      present in all spinal cord quadrants and their processes contain similar levels
      of GFAP+ intermediate filaments in both gray and white matter. These cells then
      appear to differentiate directly into regionally specialized radially oriented
      astrocytes. Oligodendrocytes labeled with the 'Olig' antibody, however, are first
      detectable in the ventral quadrant. Differentiation subsequently occurs in a
      ventral-to-dorsal sequence beginning at the interface between the gray and white
      matte. These data suggest that the origin and regulation of Xenopus astrocyte and
      oligodendrocyte differentiation are distinct.

PMID- 8549427
TI  - Conditionally immortalized oligodendrocyte cell lines migrate to different brain
      regions and elaborate 'myelin-like' membranes after transplantation into neonatal
      shiverer mouse brains.
AB  - Five immortalized oligodendrocyte cell lines, representing a spectrum of
      different stages of oligodendrocyte maturation, were transplanted into neonatal
      shiverer mouse brains and examined for their ability to survive, multiply, and
      migrate in vivo. Each of the cell lines migrated to different regions of the
      brain with remarkable consistency when injected into the mouse forebrain,
      suggesting that the cells might be responding to different environmental cues
      present in the neonatal mouse brain. These results are consistent with the fact
      that cells at different stages in the oligodendrocyte lineage probably possess
      different sets of surface molecules and receptors. Significant differences were
      also observed in the survival and proliferation of the lines examined, even when
      the lines tested had quite similar in vitro phenotypes. Interestingly, the cell
      line with the most mature in vitro phenotype, N20.1, appeared to elaborate
      membranous processes when transplanted into the brain, reminiscent of
      oligodendrocytes ensheathing axonal segments. The experiments suggest that these
      immortalized cells could be useful models to study the cellular and molecular
      mechanisms involved in the development, maturation and possibly formation of
      myelin by oligodendrocytes in the mammalian brain.

PMID- 8549428
TI  - Expression of glycolipids and myelin-associated glycoprotein during the
      differentiation of oligodendrocytes: comparison of the CG-4 glial cell line to
      primary cultures.
AB  - The expression of cerebrosides, sulfatides, gangliosides and the myelin
      associated glycoprotein (MAG) during differentiation of the CG-4 line of
      oligodendrocyte progenitors [Louis et al.: J. Neurosci Res 31: 193, 1992] was
      compared with their expression in primary cultures of oligodendrocyte precursors
      [McCarthy and de Vellis: J Cell Biol 85: 890, 1980]. When the CG-4 cells
      differentiated from bipolar progenitors to oligodendrocytes, there was a decrease
      of glucosylcerebroside synthesis and an increase in galactosylcerebroside and
      sulfatide synthesis. However, even after differentiation, the incorporation of
      [3H]galactose into these glycolipids, the amounts of galactosylcerebroside and
      sulfatide, and the galactocerebroside/sulfatide ratio were all much less than in
      primary cultures of differentiating oligodendrocytes. The major gangliosides in
      differentiated primary oligodendrocyte cultures were GM3 and GD3, and GD3 was
      also a major ganglioside in the CG-4 line. However, unlike primary cultures of O
      2A lineage cells in which GM3 synthesis increased dramatically during
      differentiation to oligodendrocytes, the CG-4 cells expressed very little GM3.
      Also, the CG-4 cells expressed larger amounts of more complex gangliosides, e.g.
      GD1b and GT1b, which were almost entirely restricted to the b-series. The amount
      of MAG expressed by the CG-4 cells increased substantially when they
      differentiated to oligodendrocytes, and it was almost all the large immature
      isoform. However, even after differentiation, the amount expressed was less than
      in differentiated primary oligodendrocyte cultures. Overall, the lower expression
      of myelin-related glycolipids and MAG by the CG-4 line suggests a lesser degree
      of differentiation in comparison to primary oligodendrocytes under the culture
      conditions of these experiments, but the larger amounts of cells available from
      the CG-4 line should be useful for investigating glycolipid and MAG function
      related to the early stages of myelinogenesis.

PMID- 8549429
TI  - Sympathetic skin response in patients with Duchenne muscular dystrophy.
AB  - To verify an eventual disfunction of the palmar sympathetic skin activity in
      Duchenne Muscular Dystrophy, we studied the sympathetic skin response (SSR) with
      endogenous, Deep Breathing (DB-SSR), exogenous Startle (SE-SSR) and Electric type
      stimuli (EE-SSR) in a group of patients and a control group. At the same time as
      the SSR, the heart rate (HR) and the basic R-R interval variation (RRIV) as well
      as the EMG diaphragmatic activity were checked. In this way, significant
      differences in the latency (p = 0.02) and amplitude (p = 0.009) values of the EE
      SSR and in the amplitude values of the SE-SSR (p = 0.001) and of the DB-SSR (p =
      0.02) were noted in the DMD group compared to the control group. In the group of
      patients the rise in latency of the EE-SSR correlates with the age (p = 0.0001)
      and with the reduction of its amplitude (p = 0.03). This last parameter
      correlates with the stage of the illness (p = 0.02). In the control group the
      mean amplitude of the EE-SSR is approximately 30% greater than that of startle
      and 50% of deep breathing. Although with amplitudes homogeneously reduced, these
      ratios are also conserved in the DMD group. Moreover the HR is greater (p =
      0.0001) whilst the RRIV is reduced (p = 0.02) in the group of the patients.
      However these parameters do not correlated either to the cardiac involvement or
      to the stage of the illness. The presence of the SSR for all the modalities of
      stimulation indicates the substantial integrity of the afferent and the efferent
      paths of the ANS. The alterations in latency and amplitude of the SSR in the
      patients could be the consequence of a lack of dystrophin at the level of the
      sudoriparous myopithelium in analogy to what has been demonstrated in the mdx
      mouse.

PMID- 8549430
TI  - Aging effects on auditory middle latency responses.
AB  - Age-related effects on auditory middle latency responses (MLR) were studied in 51
      normal subjects. The linear relationship between the amplitude of Na-Pa and Pa-Nb
      components and aging was observed, although there was no correlation between
      aging and the latencies of Na, Pa and Nb. The increases in the amplitudes of Na
      Pa and Pa-Nb components might reflect the age-related change of auditory
      responses.

PMID- 8549431
TI  - Neuromuscular fatigue and recovery in women at different ages during heavy
      resistance loading.
AB  - To examine neuromuscular fatigue and recovery 23 women, divided into three
      different age groups, i.e. young women (YW); 30 years (25.0 +/- 1.4; n = 8),
      middle-aged women (MW); 50 years (48.0 +/- 3.7; n = 7) and elderly women (EW); 70
      years (68.9 +/- 3.2; n = 8) performed a strenuous heavy resistance exercise
      protocol. The subjects performed a bilateral leg press exercise on the machine
      (David 210) for 5 sets by performing 10 repetitions in each set with the maximal
      load possible (10 RM). A recovery time of 3 minutes was allowed between the sets.
      Maximal voluntary neutral activation (integrated EMG), maximal bilateral
      isometric force, force-time and relaxation time curves of the leg extensor
      muscles were measured before, between the sets, and immediately after the loading
      as well as resting for 1 hour, 2 hours, 1 day and 2 days. The loading led to
      gradual decreases in maximal force in YW by 18.8 +/- 7.1% (p < 0.001), in MW by
      30.9 +/- 14.8% (p < 0.01) and in EW by 13.7 +/- 11.9% (p < 0.01) so that the
      relative decrease in EW was smaller (p < 0.05) than the averaged decreases in YW
      and MW. Significant (p < 0.05) decreases also took place in the maximal IEMGs of
      the exercised muscles in all groups. The force-time curve shifted also
      significantly both in YW (p < 0.001) and in MW (p < 0.001), while only a slight
      change occurred in EW. Acute recovery in maximal force was significant (p < 0.05)
      during the first hour of rest in YW and in MW but the force values in all groups
      were still after two hours of rest significantly (p < 0.05) lower than the
      preloading values. After two days of rest the force values were 93.7 +/- 11.5%
      (ns), 90.6 +/- 19.2% (p < 0.05) and 94.6 +/- 17.1% (ns) from their initial force
      values in YW, MW and EW, respectively. The present results suggest that strenuous
      heavy resistance loading both in young and middle-aged as well as in elderly
      women may result in considerable acute fatigue in the neuromuscular system
      leading not only to the decreased force production capacity of the muscles but
      also some decrease in the voluntary neural activation of the exercised muscles.
      Because the degree of acute neuromuscular fatigue and the time needed for
      recovery may differ considerably, there is a need to optimize the contents and
      the frequency of different training sessions in order to create proper strength
      training and for rehabilitation programs to match with the individual
      requirements of young, middle-aged and elderly women.

PMID- 8549432
TI  - Motor evoked potentials by magnetic stimulation in hereditary and sporadic
      ataxia.
AB  - We report the study of motor evoked potentials by magnetic stimulation in 26
      subjects with hereditary or sporadic ataxia. The subjects included 15 cases of
      late onset cerebellar ataxia (12 classified as olivopontocerebellar atrophy
      (OPCA), 3 as spinocerebellar atrophy (SCA)) and 11 cases of early onset
      cerebellar ataxia (4 Friedreich's ataxia (FA) and 7 unclassifiable in
      Friedreich's ataxia (NFA)). All subjects with FA and SCA had delayed central
      motor conduction times, more accentuated in corticospinal tracts directed to
      lumbar motoneurons. A similar but less marked slowing was observed in about half
      of the subjects with OPCA and NFA. In the last two groups the anomalies are more
      frequent in hereditary than in sporadic forms.

PMID- 8549433
TI  - Electromyography analysis of the rectus abdominis and external oblique muscles of
      children 8 to 10 years old.
AB  - The objective of this work was to study through in the electromyography the upper
      and lower umbilical rectus abdominis and the anterior and posterior parts of the
      external oblique muscles of children 8 to 10 years old. The children studied
      practice artistic and rhythmical gymnastic sports at the training and learning
      level and the study was made during abdominal exercise in the dorsal decubitus
      position on the ground and on a board. The children were divided into 2 groups:
      Group I - ten already trained children; Group II - nineteen learners. The
      participants in Group I practiced an average of 5 times a week and those in Group
      II practiced 2 times a week. The exercises analyzed were: on the ground, lifting
      the legs 30, 20 and 10 cm high with the knees flexed 90 degrees; flexing the
      trunk while maintaining the legs elevated and the knees flexed; flexing the trunk
      with homo and heterolateral rotation of the trunk while maintaining the legs
      elevated and the knees flexed. On the board, flexing the trunk with the knees
      flexed 90 degrees on top of the board inclined 30, 20 and 10 cm; flexing the
      trunk with rotation of the trunk homo and heterolateral with the knees flexed on
      the board inclined 30, 20 and 10 cm. The results showed that the superior
      umbilical part of the rectus abdominis muscle presented more intense action
      potential than the inferior-umbilical part; the more intense action potential
      occurred at the flexing of the trunk and at the flexing of the trunk with homo
      and heterolateral rotation. The anterior part of the external oblique muscle
      presented more intense action potential than the posterior part; the more intense
      action potential occurred at the flexing of the trunk and at the flexing of the
      trunk with heterolateral rotation. In both of the muscles the more intense action
      potential occurred between 45 and 60 degrees of flexing the trunk; the children
      in Group I presented more intense action potential than those in Group II; the
      exercise of lifting the flexed legs did not prove efficient for strengthening the
      analyzed abdominal muscle structure.

PMID- 8549434
TI  - Distribution of event-related potentials in patients with dementia.
AB  - Distributions of the amplitudes and the latencies of N100, P200, N200, P300 and
      mismatch negativity (MMN) were studied. The P300 latency was delayed in patients
      with dementia of the Alzheimer type (DAT) and patients with vascular dementia
      (VD). The N200 latency was delayed on Pz in DAT patients, and on Fz in VD
      patients. MMN latency was delayed on Pz in DAT patients. The P300 amplitude was
      low on Pz in DAT patients. The N100 amplitude was low in VD patients on Pz. These
      findings show the difference in cerebral lesions between DAT and VD. We suggest
      that studies of P300 amplitude, N200 latency, MMN latency and N100 amplitude
      distribution would be useful in differential diagnosis in patients with dementia.

PMID- 8549435
TI  - Electrophysiologic examination of subclinical beriberi polyneuropathy.
AB  - We performed electroneurophysiologic studies on patients with subclinical
      beriberi polyneuropathy (PNP) for early detection and early treatment of this
      disease. The subjects were 35 subclinical PNP patients admitted to the in- and
      outpatient clinics of the Dr. Soetomo Hospital, Surabaya, Indonesia, in 1989. The
      results showed that out of all the neurophysiological evaluations assessed,
      reduced amplitudes of the distal latency of the peroneal motor nerve, H-reflex,
      and pathological EMG findings in the leg muscles were the most frequently
      occurring abnormalities, followed by reduction of the proximal amplitude of the
      peroneal motor and distal amplitude of the sural sensory nerve. However the motor
      conduction velocities of the peroneal, posterior tibial and median motor nerves
      were all within normal limits. The distal amplitudes of the motor (peroneal and
      median) and sensory (sural and median) nerves were more affected than the distal
      latency times. The motor nerves were more often and more seriously affected than
      the sensoric nerves.

PMID- 8549436
TI  - Somatosensory evoked potentials and central motor pathways conduction after
      magnetic stimulation of the brain in diabetes.
AB  - Somatosensory evoked potentials (SEPs) on stimulating median and posterior tibial
      nerves, and central and spinal conduction time of the motor pathways calculated
      by means of magnetic stimulation of the cortex were valuated in diabetic
      patients. The latencies L1-Cortex and L1-C7 were significantly larger in 54
      diabetics than in controls. An increment in L1-C7 interval was found in 17
      patients, and the latency L1-Cortex was increased in 20. No patients showed
      increase in C7-Cortex interval. The increased latency L1-C7 reflects a delayed
      conduction along afferent spinal pathways in some patients with diabetes in
      contrast with the normal C7-Cortex supraspinal segment. The central and spinal
      conduction time after magnetic stimulation of the cortex were normal in 14 out of
      15 tested diabetics suggesting that central motor pathways were spared. These
      results are consistent with the existence of a central-peripheral sensory
      axonopathy in some diabetics.

PMID- 8549437
TI  - Effect of colonoscopy premedication containing diazepam and pethidine on the
      release of mast cell mediators in gut mucosal samples.
AB  - BACKGROUND AND STUDY AIMS: To date there is no information available on whether
      drugs that are commonly used in premedication for colonoscopy procedures, such as
      diazepam and pethidine, may activate intestinal mast cells and thereby give rise
      to adverse effects. Since opioids such as pethidine are well-known for their
      ability to induce histamine release from several mast cell subtypes, the present
      study investigated the effect of diazepam and pethidine, intravenously
      administered as premedication for colonoscopy, on mast cell mediator secretion
      from colonic and rectal mucosa. PATIENTS AND METHODS: The secretion of the mast
      cell mediators histamine and tryptase was followed from biopsies of patients with
      and without premedication for 30 minutes in an air-bubbled incubation medium
      (mucosa oxygenation). The mediator release and tissue histamine content were
      studied prospectively in 17 control persons (histologically normal mucosa) as
      well as in 71 patients with inflammatory bowel disease (IBD) (histologically
      uninvolved and involved tissue). RESULTS: Although a significant accumulation of
      histamine was found in inflamed IBD-tissue, the results indicate, however, that
      this premedication does not enhance the release of histamine or tryptase from gut
      mucosal samples, neither in the histologically normal mucosa of control persons
      nor in tissue unaffected or affected by inflammatory bowel disease. CONCLUSION:
      This study demonstrates that colonoscopy premedication with diazepam and
      pethidine is safe in terms of gut mucosal mast cell activation.

PMID- 8549438
TI  - Combined endoscopic ultrasound and stimulated biliary drainage in cholecystitis
      and microlithiasis--diagnoses and outcomes.
AB  - BACKGROUND AND STUDY AIMS: It is becoming increasingly evident from a number of
      studies that endoscopic ultrasound (EUS) is much more sensitive in the diagnosis
      of cholecystitis than transabdominal ultrasound (TUS). The present study was
      undertaken to further evaluate this relative sensitivity. PATIENTS AND METHODS:
      Sixty-six patients with biliary-type pain and a negative transabdominal
      ultrasound examination underwent combined endoscopic ultrasound and stimulated
      biliary drainage (EUS/SBD). Stimulated biliary drainage was obtained following
      intraduodenal infusion of magnesium sulfate or intravenous sincalide, a CCK
      analogue. EUS was considered positive if sludge or small stones were seen in the
      gallbladder. Stimulated biliary drainage was considered positive if calcium
      bilirubinate granules or cholesterol crystals were seen on microscopic
      examination of aspirated bile. RESULTS: At operation, 61 of the patients had
      cholecystitis documented histologically. Fifty-eight of the patients had
      gallbladder sludge or small stones on EUS. One patient had a negative EUS, but
      had calcium bilirubinate granules in the bile. Twenty-one patients were followed
      post-operatively for a period of seven to 17 months, with an average of 10.5
      months. Nineteen patients (90.5%) remain free of biliary pain. CONCLUSIONS:
      Combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD) had a
      high sensitivity of 92.4% and a positive predictive value of 100% in the
      diagnosis of cholecystitis when transabdominal ultrasound was negative. A
      significant majority (90.5%) of patients with positive EUS/SBD who underwent
      cholecystectomy had resolution of their biliary pain.

PMID- 8549439
TI  - Effectiveness of endoscopic ultrasonography in the diagnosis of
      choledocholithiasis prior to laparoscopic cholecystectomy.
AB  - BACKGROUND AND STUDY AIMS: To reduce the rate of conversion to open
      cholecystectomy, and to avoid retained bile duct stones, it is essential to
      detect choledocholithiasis prior to laparoscopic cholecystectomy. The aim of the
      present study was to evaluate the usefulness and safety of performing endoscopic
      ultrasonography (EUS) for the diagnosis of choledocholithiasis prior to
      laparoscopic cholecystectomy. PATIENTS AND METHODS: One hundred thirty-two
      patients with symptomatic cholelithiasis were evaluated prospectively using
      standard abdominal ultrasonography (US), US plus EUS, and US plus endoscopic
      retrograde cholangiography (ERC) for the detection of choledocholithiasis prior
      to laparoscopic cholecystectomy. RESULTS: Twenty-eight patients (21.2%) had
      choledocholithiasis, and six patients with common bile duct stones had normal
      sized ducts on US. The common bile duct was successfully examined in all patients
      using EUS, but only in 65.9% of patients when US was used and 94.7% of patients
      when ERC was used. US plus EUS detected choledocholithiasis in 25 of 28 patients
      (89.3%), US in 19 of 28 patients (67.9%), and US plus ERC in 26 of 28 patients
      (92.9%). While no complications as a result of EUS were encountered,
      complications resulting from ERC occurred in seven patients (5.3%), including
      cholecystitis in two patients, cholangitis in three patients, and pancreatitis in
      two patients. In view of the complication and failure rates, EUS appears to offer
      significant advantages over ERC. These results suggest that EUS is more sensitive
      than standard abdominal ultrasonography, and as sensitive as ERC. CONCLUSIONS:
      EUS appears to be as sensitive as, and safer than, ERC in the detection of
      choledocholithiasis prior to laparoscopic cholecystectomy.

PMID- 8549440
TI  - Endoscopic incision of Zenker's diverticula.
AB  - BACKGROUND AND STUDY AIMS: The endoscopic treatment of symptomatic
      pharyngoesophageal diverticula (PED) with rigid instruments involves the incision
      of the septum between the diverticulum and the esophageal lumen, within which the
      cricopharyngeal muscle is present. The aim of this study is to report on the
      feasibility and efficacy of our method using flexible endoscopy and an electro
      surgery system with minimal trauma to the patients. PATIENTS AND METHODS: Forty
      two patients (13 female, 29 male) with symptomatic pharyngoesophageal diverticula
      underwent endoscopic treatment. The average age of the patients was 68.4 years
      (range 46 to 102 years) and 26 of them (61%) had concomitant cardiopulmonary
      diseases. The procedure consisted of endoscopic incision of the septum with a
      needle knife, using cutting/coagulation current. It was performed under
      preparation for routine endoscopic examination. All patients were clinically and
      endoscopically evaluated at two and four weeks, and afterwards followed
      clinically at 12, 24, and 60 months after the procedure. RESULTS: The endoscopic
      incision was performed in one to live sessions (mean of 1.8 session per patient).
      Two complications (one cervical emphysema, and one hemorrhage) were managed
      clinically. Dysphagia disappeared in all patients soon after the treatment,
      although the post-operative radiological and endoscopic controls revealed the
      presence of a remaining diverticulum. Manometric findings disclosed a significant
      reduction in upper esophageal sphincter pressures in all five patients after
      endoscopic incision. Mean follow-up was 38 months. There was recurrence of
      dysphagia in three patients (7.1%) at 12, 22, and 60 months after the procedure.
      They experienced relief of dysphagia after a repeated endoscopic incision.
      CONCLUSIONS: Endoscopic incision of PED using flexible equipment proved to be a
      highly efficient and safe method of treating symptomatic disease. It should be
      considered as an alternative therapy for Zenker's diverticula, especially for
      patients at a high surgical risk.

PMID- 8549441
TI  - Flexible endoscopic treatment of Zenker's diverticulum: a new approach.
AB  - BACKGROUND AND STUDY AIMS: In the past, a number of treatment modalities have
      been used for the management of a Zenker's diverticulum. These include
      transcervical diverticulectomy, myotomy, or laser or diathermy treatment via
      rigid endoscopes. Up to the present, no reports of the treatment of a Zenker's
      diverticulum with a flexible endoscope have been published. PATIENTS AND METHODS:
      In this study, we present the results of our first 20 patients (13 male; mean age
      82 years) prospectively treated with a flexible endoscope applied through
      diathermy. All patients had significant symptoms such as dysphagia, recurrent
      aspiration pneumonia and/or weight loss. RESULTS: Treatment using a mean of three
      sessions per patient was successful, with a good symptomatic response in all
      subjects. There were no severe complications associated with the therapy. Four
      patients complained about a sore throat for a few days. During follow-up (mean 6
      7 months), three patients died due to unrelated causes, and 17 remained
      asymptomatic. CONCLUSIONS: An important advantage is that it is possible to
      perform the treatment without general anesthesia, and therefore also in patients
      whose general health is poor. The technique can easily be performed in an
      interventional endoscopy unit. Our first experiences show that flexible
      endoscopic treatment is an effective and relatively safe method.

PMID- 8549442
TI  - Diagnosis and management of choledocholithiasis in the era of laparoscopic
      cholecystectomy: an endoscopist's perspective.

PMID- 8549443
TI  - Reducing treatment of Zenker's diverticulum to the essentials: the flexible
      endoscopic approach.

PMID- 8549444
TI  - Dilation of difficult gastrointestinal strictures using a modified wire-guided
      technique.
AB  - We describe here 18 patients with gastrointestinal strictures through which a
      standard guide wire could not be passed, and which were dilated using a modified
      technique. After a 0.035" guide wire had been passed through a 5-Fr metal-tipped
      catheter, the narrow strictures were dilated using a 10-Fr biliary dilator. A
      modified Savary-Gilliard guide wire (olive-tipped with a hole) was passed over
      the 0.035" guide wire beyond the stricture. After removing the 0.035" guide wire,
      the strictures were dilated with Savary-Gilliard dilators passed over the olive
      tipped guide wire. Seventeen patients had upper gastrointestinal strictures, and
      one had a sigmoid colon stricture. The strictures were caused by tumor in two,
      radiation therapy in six, esophagogastric resection for cancer in five, and a
      combination of two or more factors in five patients. The modified technique was
      successful in 17 patients, without any complications. Adequate symptomatic relief
      was achieved in 15 patients.

PMID- 8549445
TI  - Update on clinical aspects and technology in endoscopic surgery.

PMID- 8549446
TI  - Development of esophageal cancer after endoscopic injection sclerotherapy for
      esophageal varices: three case reports.
AB  - We report here three cases of squamous-cell carcinoma of the esophagus following
      endoscopic injection sclerotherapy for esophageal varices. All three patients
      were men and cigarette smokers, with a mean age of 58.3 +/- 5.0 years. Hepatitis
      B and C virus infection tests were negative, and alcoholic cirrhosis was present
      in each patient. The interval between sclerotherapy and the development of
      carcinoma was 9, 10, and 33 months, in the respective cases. The sclerosant used
      was 5% ethanolamine oleate with a mean total volume of 51.0 +/- 18.9 ml. While we
      have no evidence of a direct relationship between sclerotherapy and esophageal
      cancer, in patients with alcoholic cirrhosis who have risk factors for esophageal
      cancer there may be an acceleration of the potential malignancy, as a result of
      the chronic inflammation related to sclerotherapy. Such patients should be
      closely followed, using endoscopy.

PMID- 8549447
TI  - Colocutaneous fistula formation following polypropylene mesh placement for repair
      of a ventral hernia: diagnosis by colonoscopy.

PMID- 8549448
TI  - A case of esophageal obstruction after ingestion of a granular laxative.

PMID- 8549449
TI  - Endoscopic management of obstructive jaundice due to portal cavernoma.

PMID- 8549450
TI  - Endoscopic removal of an Angelchik prosthesis after migration through the gastro
      oesophageal junction.

PMID- 8549451
TI  - Cystic duct remnant duodenal fistulization as a cause of misconceived endoscopic
      sphincterotomy and the consequent massive bleeding.

PMID- 8549452
TI  - Endoscopic drainage of a pancratic abscess with a transduodenal nasopancreatic
      catheter.

PMID- 8549453
TI  - Endoscopic diagnosis of a retained surgical sponge following intra-abdominal
      surgery.

PMID- 8549454
TI  - Giant polyposis ulcerative colitis imitating colonic carcinoma: two cases.

PMID- 8549455
TI  - Application of biologic markers to studies of environmental risks in children and
      the developing fetus.
AB  - Young children and the developing fetus may be more susceptible to effects of
      environmental toxicants than adults due to differential exposure patterns and
      developmental immaturities. Biologic markers offer the potential of quantitative
      dosimeters of biologic dose and/or indices of biologic effect associated with
      fetal/childhood exposures. They can facilitate evaluation of interindividual
      variability in response and the magnitude of age-related susceptibilities. Thus
      far, biologic markers have not been widely used in developmental epidemiology of
      environmental exposures. Research by our group and others has seen elevations in
      biologic markers in samples from children and fetal tissue associated with a
      spectrum of environmental exposures, including tobacco smoke (active and
      passive), ambient pollution, and dietary contaminants. Studies also suggest that
      biologic markers can provide powerful dosimeters for investigating reproductive
      effects. Validation of biologic markers offering the greatest promise for
      developmental epidemiology is needed.

PMID- 8549456
TI  - Assessment of environmental and genetic factors in the etiology of childhood
      cancers: the Childrens Cancer Group epidemiology program.
AB  - The occurrence of cancer during childhood represents one of the leading causes of
      death within the pediatric and adolescent age group. It is estimated that
      approximately 8000 children will be diagnosed annually with cancer in the United
      States. Epidemiologic research addressing the etiology of childhood cancer has
      been limited because of the difficulties in identifying a sufficiently large
      study population. Moreover, the use of retrospectively ascertained childhood
      cancer cases in epidemiologic investigations has restricted the incorporation of
      biological and clinical parameters. The Childrens Cancer Group has developed an
      active program in epidemiologic research, with over a decade of experience
      demonstrating the feasibility and strengths of conducting analytic epidemiologic
      studies within a cooperative clinical trials network. The availability of
      detailed clinical and biologic data on cases diagnosed within the cooperative
      group facilitates the transfer of state-of-the-art technology to epidemiologic
      research.

PMID- 8549458
TI  - Understanding outrage: how scientists can help bridge the risk perception gap.

PMID- 8549457
TI  - Growth abnormalities in the population exposed in utero and early postnatally to
      polychlorinated biphenyls and dibenzofurans.
AB  - This article reviews the findings in children exposed to various levels of
      polychlorinated biphenyls (PCBs) and related compounds in utero and early
      postnatally. Yu-Cheng ("oil-disease") mothers were Taiwanese women exposed to
      PCBs and their heat-degradation products from the ingestion of contaminated rice
      oil in 1979. Children of these mothers were born growth retarded, with dysmorphic
      physical findings, and delayed cognitive development compared with unexposed
      children. In this article, findings in Yu-Cheng children born between 1978 and
      1985 are summarized and compared with two other well-documented cohorts of
      children prenatally exposed to different levels of PCBs. Results of the
      investigation in Yu-Cheng children will provide important information about the
      toxicities, health effects, and mechanisms of PCB/PCDF exposure and demonstrate
      that the developing human is more sensitive than the adult to the toxic effects
      of these chemicals.

PMID- 8549459
TI  - Communicating with the public on issues of science and public health.

PMID- 8549460
TI  - Children--unique and vulnerable. Environmental risks facing children and
      recommendations for response.
AB  - Children may be more susceptible to exposures to environmental toxins than adults
      and may be more vulnerable to their effects. Because of this, the health care
      community and those responsible for children need to be alert to possible
      environmental factors in identifying and responding to the health problems of
      children. Their focus should be on the causes of the health problem, emphasizing
      environmental sources, and not on simply treating the symptoms.

PMID- 8549461
TI  - Uncertain risks and the risks of certainty.

PMID- 8549463
TI  - How should federal policy reflect recent research in the area of intrauterine
      exposure to environmental hazards?
AB  - Present policy neither evaluates nor adequately protects the fetus from the
      effects of intrauterine exposure to environmental hazards. Some examples are
      intrauterine lead and methylmercury exposure and intrauterine PCB exposures. A
      sound policy based on a few basic principles can be developed to protect the
      fetus from harm from intrauterine exposures.

PMID- 8549462
TI  - Neurobehavioral effects of developmental methylmercury exposure.
AB  - Methylmercury (MeHg) is a global environmental problem and is listed by the
      International Program of Chemical Safety as one of the six most dangerous
      chemicals in the world's environment. Human exposure to MeHg primarily occurs
      through the consumption of contaminated food such as fish, although catastrophic
      exposures due to industrial pollution have occurred. The fetus is particularly
      sensitive to MeHg exposure and adverse effects on infant development have been
      associated with levels of exposure that result in few, if any, signs of maternal
      clinical illness or toxicity. High levels of prenatal exposure in humans result
      in neurobehavioral effects such as cerebral palsy and severe mental retardation.
      Prenatal exposure to MeHg in communities with chronic low-level exposure is
      related to decreased birthweight and early sensorimotor dysfunction such as
      delayed onset of walking. Neurobehavioral alterations have also been documented
      in studies with nonhuman primates and rodents. Available information on the
      developmental neurotoxic effects of MeHg, particularly the neurobehavioral
      effects, indicates that the fetus and infant are more sensitive to adverse
      effects of MeHg. It is therefore recommended that pregnant women and women of
      childbearing age be strongly advised to limit their exposure to potential sources
      of MeHg. Based on results from human and animal studies on the developmental
      neurotoxic effects of methylmercury, the accepted reference dose should be
      lowered to 0.025 to 0.06 MeHg microgram/kg/day. Continued research on the
      neurotoxic effects associated with low level developmental exposure is needed.

PMID- 8549464
TI  - The concern for developmental neurotoxicology: is it justified and what is being
      done about it?
AB  - In general, it is believed that the possibility of an adverse developmental
      outcome following conception is relatively high. In most cases, the cause of the
      defect is not clear, although exposure to chemical agents at a critical period
      during development has been proposed to play a significant role. Consequently,
      regulatory agencies such as the U.S. Environmental Protection Agency (U.S. EPA)
      have promulgated testing guidelines for assessing developmental neurotoxicity of
      chemicals in animal testing protocols. Concerns have been expressed about the use
      of behavioral tests to evaluate chemicals for developmental neurotoxicity, since
      some investigators believe that they lack predictive validity for human
      developmental neurotoxicity. Other investigators have indicated that results from
      such studies are difficult to interpret because of a lack of standardization and
      sensitivity of the tests. Furthermore, it has been argued that the developing
      organism is not especially sensitive to chemicals or, if effects are observed,
      the developing organism is capable of compensating for the deficit. Recent
      research, however, has adequately demonstrated that developing organisms are
      especially vulnerable to chemical agents if the exposure occurs at a critical
      period during development, while other studies have supported the assumption that
      functional or behavioral effects observed in animal models can be extrapolated to
      humans. These findings support the routine assessment of chemicals for
      developmental neurotoxicity using functional end points and suggest that
      currently available methods could be used to determine more precisely the
      mechanism of chemical-induced developmental defects.

PMID- 8549465
TI  - Risk assessment, a community perspective.

PMID- 8549466
TI  - Pesticides--the NAS report: how can the recommendations be implemented?

PMID- 8549467
TI  - Neural tube defects--why are rates high among populations of Mexican descent?

PMID- 8549468
TI  - Looking for causes of neural tube defects: where does the environment fit in?
AB  - The neural tube defects anencephaly and spina bifida are important causes of
      infant mortality and morbidity. Recent studies suggest that many of these defects
      can be prevented by the periconceptional use of folic acid. At the same time, we
      do not know what causes most cases of neural tube defects and there is evidence
      to suggest that they are etiologically heterogeneous. Additional research needs
      to be directed toward the role of occupational and environmental exposures in the
      etiology of these defects. Importantly, studies need to examine embryologically
      and anatomically specific types of defects and develop accurate information on
      biologically relevant exposures. Exposures toward which attention needs to be
      directed include organic solvents; agricultural chemicals, including pesticides;
      water nitrates; heavy metals such as mercury; ionizing radiation; and water
      disinfection by products. We also recommend that additional attention be paid to
      mechanisms of neural tube closure and to the potential role of genetic
      heterogeneity in the absorption and metabolism of xenobiotics and in their
      effects on the neural tube.

PMID- 8549469
TI  - Can laboratory animal carcinogenicity studies predict cancer in exposed children?
AB  - A key to the prevention of childhood cancer is the control of carcinogens to
      which children are exposed. The first step in this process is to identify those
      chemicals that are likely to cause cancer in children. The best way to identify
      carcinogens, today, is the use of the rodent lifetime cancer test--the bioassay.
      The test has vocal critics, but is adequately reliable if properly used. Perhaps
      the major criticism concerns the use of the maximum tolerated dose as the highest
      dose tested. Critics claim that this dose causes cellular killing. The resultant
      cellular proliferation "fixes" preexisting mutations that can lead to cancer.
      This occurs but in a small fraction of the tests, and the high dose is necessary
      to achieve statistical sensitivity. All human carcinogens have been shown, when
      properly studied, to be carcinogenic in rodents. Many human carcinogens were
      first shown to cause cancer in rodent tests. Regulators rarely ban chemicals that
      have been demonstrated to be carcinogenic. Further, most chemicals in use today
      have not been properly tested. The potential errors in the rodent cancer test
      seem small when compared to the errors in the economic projections of the effects
      of restricting chemicals. Although not perfect, the rodent cancer test, when used
      properly, can help protect our children, and us, from cancer.

PMID- 8549472
TI  - Environmental poisoning of children--lessons from the past.
AB  - Children have physiologic and behavioral characteristics that make them
      vulnerable to damage from environmental chemicals. In the past, there have been
      episodes in which children became ill or died from environmental exposures that
      spared adults or affected them less severely. Among the characteristics leading
      to children's sensitivity are their limited diets, dividing cells,
      differentiating organs and organ systems, slow or absent detoxification
      mechanisms, long life expectancy with the resulting ability to express damage
      with delayed consequences, and the severe metabolic demands of growth. There have
      been large outbreaks of poisonings involving children in Asia and Turkey, and
      some of the less obvious effects of chemicals have appeared in children in the
      United States. Although the United States has been spared a widespread outbreak
      of severe poisoning, such an incident is possible and would likely have greater
      consequences for children than adults.

PMID- 8549470
TI  - Childhood cancer: overview of incidence trends and environmental carcinogens.
AB  - An estimated 8000 children 0 to 14 years of age are diagnosed annually with
      cancer in the United States. Leukemia and brain tumors are the most common
      childhood malignancies, accounting for 30 and 20% of newly diagnosed cases,
      respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children
      increased slightly from 12.8 to 14.1/100,000. Increases are suggested for
      leukemia, gliomas, and, to a much lesser extent, Wilms' tumor. There are a few
      well-established environmental causes of childhood cancer such as radiation,
      chemotherapeutic agents, and diethylstilbestrol. Many other agents such as
      electromagnetic fields, pesticides, and some parental occupational exposures are
      suspected of playing roles, but the evidence is not conclusive at this time. Some
      childhood exposures such as secondhand cigarette smoke may contribute to cancers
      that develop many years after childhood. For some exposures such as radiation and
      pesticides data suggest that children may be more susceptible to the carcinogenic
      effects than similarly exposed adults.

PMID- 8549471
TI  - The role of nutrition in mitigating environmental insults: policy and ethical
      issues.

PMID- 8549473
TI  - Nutrition and lead: strategies for public health.

PMID- 8549475
TI  - Air toxics and asthma: impacts and end points.
AB  - The National Urban Air Toxics Research Center (NUATRC) hosted a
      medical/scientific workshop focused on possible asthma/air toxics relationships,
      with the results of the NUATRC's first research contract with the University of
      Cincinnati as the point of discussion. The workshop was held at the Texas Medical
      Center on 4 February 1994 and featured presentations by distinguished academic,
      government, and industry scientists. This one-day session explored the impact of
      various environmental factors, including air toxics, on asthma incidence and
      exacerbation; an emphasis was placed on future research directions to be pursued
      in the asthma/air toxics area. A key research presentation on the association of
      air toxics and asthma, based on the study sponsored by NUATRC, was given by Dr.
      George Leikauf of the University of Cincinnati Medical Center. Additional
      presentations were made by H. A. Boushey, Jr., Cardiovascular Research
      Institute/University of California at San Francisco, who spoke on of the Basic
      Mechanisms of Asthma; K. Sexton, U.S. Environmental Protection Agency, who spoke
      on hazardous air pollutants: science/policy interface; and D. V. Bates,
      Department of Health Care and Epidemiology at the University of British Columbia,
      who spoke on asthma epidemiology. H. Koren, U.S. Environmental Protection Agency,
      and M. Yeung, of the Respiratory Division/University of British Columbia,
      Vancouver General Hospital, discussed occupational health impacts on asthma.
      Doyle Pendleton, Texas Natural Resource Conservation Commission, reviewed air
      quality measurements in Texas. The information presented at the workshop
      suggested a possible association of asthma exacerbations with ozone and
      particulate matter (PM10); however, direct relationships between worsening asthma
      and air toxic ambient levels were not established. Possible respiratory health
      effects associated with air toxics will require considerably more investigation,
      especially in the area of human exposure assessment. Two major recommendations
      for future research resulted from this workshop and an accompanying NUATRC
      Scientific Advisory Panel meeting: a need for more complete individual personal
      exposure assessments so that accurate determinations of actual personal exposures
      to various pollutants can be made; and a need for field experiments utilizing
      biomarkers of exposure and effect to more accurately assess the extent and
      variability of the biological effects, if any, of individual air toxics.

PMID- 8549474
TI  - Chemical contaminants in human milk: an overview.
AB  - This review contains a succinct overview of the nature and extent of the problem
      of contamination of human milk with environmental and occupational chemicals,
      excluding drugs. Factors influencing the levels of contaminants in breast milk
      are discussed. Also, data on major chemicals of concern with potential health
      risk(s) to the general population and risk-benefit considerations are dealt with
      briefly. Based on the available data on the subject, research needs have been
      identified and policy recommendations are suggested.

PMID- 8549476
TI  - Science and policy in regulatory decision making: getting the facts right about
      hazardous air pollutants.
AB  - Hazardous air pollutants are regulated under Title III of the 1990 Clean Air Act
      Amendments. The Amendments replace the risk-based approach mandated in the 1977
      Amendments with a prescriptive, technology-based approach requiring that maximum
      achievable control technology (MACT) be applied to all major industrial sources
      of 189 hazardous air pollutants. The change reflects political, rather than
      scientific consensus that the public health benefits justify the costs. The
      choice is put into perspective by looking at the interface between science and
      policy that occurs as part of regular decisionmaking. Particular emphasis is
      given to examining the interrelationships among facts (science), judgments
      (science policy), and policy (values) in the context of the risk assessment
      paradigm. Science and policy are discussed in relation to Title III, contrasting
      the political consensus for action with the scientific uncertainty about risks
      and benefits. It is argued that a balanced research program is needed to get the
      facts right about hazardous air pollutants, including research to meet statutory
      requirements, to reduce uncertainties in risk assessment, and to address
      strategic issues.

PMID- 8549477
TI  - Air toxics: sources and monitoring in Texas.
AB  - Since the late 1980s, federal legislation has required industries to publicly
      report their annual emissions of toxic compounds. Industry reports show the
      largest contributor to toxic emission levels in Texas is the massive
      concentration of petrochemical industries along the Gulf Coast. It is interesting
      to note that although Texas produces over 50% of the nation's synthetic
      chemicals, it discharges less than 8% of the nation's toxic emissions. However,
      in response to growing concerns about the effects of these toxic emissions, the
      Texas Natural Resource Conservation Commission (TNRCC) initiated a long-term
      program for monitoring toxic chemicals in the air. This article provides details
      of this monitoring program as well as industry-funded toxic monitoring networks
      in Texas. This includes information on the technology currently being used for
      sample collection and analysis as well as plans for implementing methods that are
      on the technological horizon. Finally, details of some key measurements from the
      state's air toxics monitoring network will be provided along with an explanation
      of how they impact current air quality trends in Texas.

PMID- 8549478
TI  - Basic mechanisms of asthma.
AB  - Results of studies of the epidemiology, physiology, histopathology, and cell
      biology of asthma have revised our conception of the disease. Epidemiologic
      studies have shown asthma to be an important cause of death, suffering, and
      economic hardship. Physiologic studies have shown that asthma is a chronic
      illness characterized by persistent bronchial hyperreactivity. Histopathologic
      studies have shown characteristic changes: epithelial damage, deposition of
      collagen beneath the basement membrane, eosinophilic and lymphocytic
      infiltration, and hypertrophy and hyperplasia of goblet cells, submucosal glands,
      and airway smooth muscle. Studies of the functions of cells in the airway mucosa
      suggest that asthma may be fundamentally mediated by a difference in the type of
      lymphocyte predominating in the airway mucosa but may also involve complex
      interactions among resident and migratory cells. Asthma may thus result from
      sensitization of a subpopulation of CD4+ lymphocytes, the Th2 subtype, in the
      airways. These lymphocytes produce a family of cytokines that favor IgE
      production and the growth and activation of mast cells and eosinophils, arming
      the airways with the mechanisms of response to subsequent reexposure to the
      allergen. This conceptual model has stimulated research along lines that will
      almost certainly lead to powerful new treatments, and it has already put current
      therapies in a new light, clarifying the role of antinflammatory agents,
      especially of inhaled corticosteroids. This conceptual model has some
      limitations: it ignores new evidence on the role of the mast cell in producing
      cytokines and depends on results of studies of the effects of inhalation of
      allergen, although most asthma exacerbations are provoked by viral respiratory
      infection. Preliminary studies suggest that viral infection and allergen
      inhalation may involve the activation of different pathways, with viral infection
      activating production of cytokines by airway epithelial cells. Similar study of
      the mechanisms activated by inhalation of air toxics may provide important clues
      as to how they might induce or exacerbate asthma.

PMID- 8549479
TI  - Associations between criteria air pollutants and asthma.
AB  - The evidence that asthma is increasing in prevalence is becoming increasingly
      compelling. This trend has been demonstrated not only in the United States, but
      also in the United Kingdom, New Zealand, Australia, and several other Western
      countries. In the United States, the increase is largest in the group under 18
      years of age. There is mounting evidence that certain environmental air
      pollutants are involved in exacerbating asthma. This is based primarily on
      epidemiologic studies and more recent clinical studies. The U.S. Clean Air Act of
      1970 provides special consideration to the class of outdoor air pollutants
      referred to as criteria pollutants, including O3, sulfur dioxide (SO2),
      particulate matter (PM), NOx, CO, and Pb. Standards for these pollutants are set
      by the U.S. Environmental Protection Agency with particular concern for
      populations at risk. Current evidence suggests that asthmatics are more sensitive
      to the effects of O3, SO2, PM, and NO2, and are therefore at risk. High SO2 and
      particulate concentrations have been associated with short-term increases in
      morbidity and mortality in the general population during dramatic air pollution
      episodes in the past. Controlled exposure studies have clearly shown that
      asthmatics are sensitive to low levels of SO2. Exercising asthmatics exposed to
      SO2 develop bronchoconstriction within minutes, even at levels of 0.25 ppm.
      Responses are modified by air temperature, humidity, and exercise level. Recent
      epidemiologic studies have suggested that exposure to PM is strongly associated
      with morbidity and mortality in the general population and that hospital
      admissions for bronchitis and asthma were associated with PM10 levels. In
      controlled clinical studies, asthmatics appear to be no more reactive to aerosols
      than healthy subjects. Consequently, it is difficult to attribute the increased
      mortality observed in epidemiologic studies to specific effects demonstrated in
      controlled human studies. Epidemiologic studies of hospital admissions for asthma
      have implicated O3 as contributing to the exacerbation of asthma; however, most
      study designs could not separate the O3 effects from the concomitant effects of
      acid aerosols and SO2. Controlled human clinical studies have suggested that
      asthmatics have similar changes in spirometry and airway reactivity in response
      to O3 exposure compared to healthy adults. However, a possible role of O3 in
      worsening atopic asthma has recently been suggested in studies combining allergen
      challenge following exposure to O3. Attempts at identification of factors that
      predispose asthmatics to responsiveness to NO2 has produced inconsistent results
      and requires further investigation. In summary, asthmatics have been shown to be
      a sensitive subpopulation relative to several of the criteria pollutants. Further
      research linking epidemiologic, clinical, and toxicologic approaches is required
      to better understand and characterize the risk of exposing asthmatics to these
      pollutants.

PMID- 8549480
TI  - Observations on asthma.
AB  - A review of the present understanding of asthma leads to the following
      conclusions: an elevated IgE is the principal risk factor in the development of
      childhood asthma; secondary exposure to a wide range of environmental agents
      (including indoor bioallergens) accounts for the variations in prevalence;
      prevalence (defined by a positive answer to the question "Have you ever had
      doctor-diagnosed asthma?") ranges between 4 and 8% in children. Black children
      have a slightly higher prevalence than white children in the United States, and
      in both races boys have a higher prevalence than girls. A high prevalence is
      found in Puerto Rican children in the United States. Patterns of utilization of
      health care resources (hospital emergency departments, individual physicians,
      etc.) are dependent on economic circumstances. Low-income children have higher
      annual morbidity (days in hospital, days off school, etc.) than higher income
      children and are more dependent on hospital emergency departments for primary
      care. Relatively little is known about nonatopic asthma in adults, although virus
      infections and occupational exposures play some part in its induction. There are
      some striking examples of asthma attack periodicity, and much may be learned from
      these. Hospital admissions for asthma have increased in many regions over the
      past 15 years; it is unlikely that this represents the increased admission of
      milder cases and hence would indicate that asthma has become more severe. This is
      likely to be a more sensitive indicator of change than mortality. Associations
      between indices of health effects and air pollutants indicate that these are
      probably playing a role in the worsening of asthma. Adverse effects related to
      SO2 and NO2 exposures have been documented, and fine particulate pollution (PM10)
      is also associated with worsening of asthma. Ozone is an intense respiratory
      irritant, and, together with acid aerosols, may well be playing a role in the
      worsening of asthma. It is not known whether any of these agents are affecting
      prevalence.

PMID- 8549481
TI  - Occupational asthma.
AB  - Many toxic compounds found in air emissions may induce bronchoconstriction. In
      the workplace, workers are exposed to these compounds, often in much higher
      concentrations. Some of these compounds act as sensitizers. Of these, some
      compounds induce asthma by producing specific IgE antibodies to the compound or
      its protein conjugate, while others induce asthma through yet unidentified
      immunologic mechanisms. Some compounds, when inhaled in high concentrations, act
      as irritants and produce bronchoconstriction probably by inducing acute airway
      inflammation. The latter condition is called Reactive Airways Dysfunction
      Syndrome (RADS) or irritant-induced asthma. Occupational asthma is an excellent
      model to study the pathogenesis and the natural history of adult onset asthma
      because the responsible agent can be identified, complete avoidance is possible,
      and exposure can be measured or estimated.

PMID- 8549482
TI  - Environmental health and Hispanic children.
AB  - There are numerous indicators that Hispanics face a disproportionate risk of
      exposure to environmental hazards. Ambient air pollution, worker exposure to
      chemicals, indoor air pollution, and drinking water quality are among the top
      four threats to human health and are all areas in which indicators point to
      elevated risk for Hispanic populations. These data, juxtaposed with data on the
      health status of Hispanics, tell us that the environmental health status of
      Hispanics and their children is poor. At the same time, significant inadequacies
      in the collection of data on Hispanics make it difficult to make improving
      Hispanic environmental health status a priority. These inadequacies include the
      failure to use Hispanic identifiers in data collection and failure to collect
      sample sizes large enough to allow for breakouts of data by Hispanic subgroup. In
      addressing environmental justice issues, the U. S. Environmental Protection
      Agency (U.S. EPA) and the Department of Health and Human Services (DHHS) should
      prioritize improving the quantifiability of environmental exposures and risk
      based on race or ethnicity. However, improving data should not be the
      prerequisite to significant, affirmative steps by DHHS and U.S. EPA to address
      environmental and environmental health problems facing Hispanic communities. In
      particular, a health-based approach to environmental justice should be the
      priority.

PMID- 8549484
TI  - Preventing child exposures to environmental hazards: research and policy issues.

PMID- 8549485
TI  - The disproportionate impact of environmental health threats on children of color.
AB  - Children receive greater exposures to environmental pollutants present in air,
      food, and water because they inhale or ingest more air, food, or water on a body
      weight basis than adults do. Communities of color are disproportionately exposed
      to hazardous wastes, dioxin, and air pollution. Existing data demonstrate that
      children of color are the subgroup of the population most exposed to certain
      pollutants, including lead, air pollution, and pesticides. Government standards
      do not take into account children's differential exposures or the cumulative
      nature of these exposures. Federal regulations fail to protect the most highly
      exposed and most sensitive subgroups of the population. More often than not this
      group is children of color.

PMID- 8549486
TI  - Age-specific oncogenesis: the genetics of cancer susceptibility.
AB  - Cancer is considered to be a multifactorial disease in which a host cell is
      transformed from normal to malignant as a result of complex interactions of
      external (environmental) stimuli and cancer-predisposing or cancer-suppressing
      genes. Although certain chemical carcinogens and ionizing radiation are known to
      cause specific alterations at the level of the gene, other correlations are less
      clear. Not infrequently, cancer is found to aggregate in families in an
      apparently nonrandom fashion. It has been through the study of such families that
      our understanding of the genetic events leading to cancer has developed. Both
      common and rare tumors may occur together in familial-cancer families.
      Frequently, tumors occur at an earlier age than one would expect in the general
      population; often, multiple tumors of different organs develop in a particular
      affected family member. Recent advances in the genetics of familial cancer
      syndromes have led to the possibility to perform genetic testing on unaffected
      relatives who might carry a genetic defect that predisposes them to cancer.
      Complex ethical, social, and legal implications arise from these new technical
      advances.

PMID- 8549483
TI  - Evaluation of a possible association of urban air toxics and asthma.
AB  - The prevalence of asthma, measured either as the frequency of hospital admissions
      or number of deaths attributed to asthma, has increased over the last 15 to 20
      years. Rapid increases in disease prevalence are more likely to be attributable
      to environmental than genetic factors. Inferring from past associations between
      air pollution and asthma, it is feasible that changes in the ambient environment
      could contribute to this increase in morbidity and mortality. Scientific
      evaluation of the links between air pollution and the exacerbation of asthma is
      incomplete, however. Currently, criteria pollutants [SOx, NOx, O3, CO, Pb,
      particulate matter (PM10)] and other risk factors (exposure to environmental
      tobacco smoke, volatile organic compounds, etc.) are constantly being evaluated
      as to their possible contributions to this situation. Data from these studies
      suggest that increases in respiratory disease are associated with exposures to
      ambient concentrations of particulate and gaseous pollutants. Similarly, exposure
      to environmental tobacco smoke, also a mixture of particulate and gaseous air
      toxics, has been associated with an increase in asthma among children. In
      addition, current associations of adverse health effects with existing pollution
      measurements are often noted at concentrations below those that produce effects
      in controlled animal and human exposures to each pollutant alone. These findings
      imply that adverse responses are augmented when persons are exposed to irritant
      mixtures of particles and gases and that current measurements of air pollution
      are, in part, indirect in that the concentrations of criteria pollutants are
      acting as surrogates of our exposure to a complex mixture. Other irritant air
      pollutants, including certain urban air toxics, are associated with asthma in
      occupational settings and may interact with criteria pollutants in ambient air to
      exacerbate asthma. An evaluation of dose-response information for urban air
      toxics and biological feasibility as possible contributors to asthma is therefore
      needed. However, this evaluation is compounded by a lack of information on the
      concentrations of these compounds in the ambient air and their effects on asthma
      morbidity and mortality. Through an initial review of the current toxicological
      literature, we propose a tentative list of 30 compounds that could have the
      highest impact on asthma and respiratory health. These compounds were selected
      based on their ability to induce or exacerbate asthma in occupational and
      nonoccupational settings, their allergic potential and ability to react with
      biological macromolecules, and lastly, their ability to irritate the respiratory
      passages. We recommend better documentation of exposure to these compounds
      through routine air sampling and evaluation of total exposure and further
      evaluation of biological mechanisms through laboratory and epidemiological
      studies directed specifically at the role these substances play in the induction
      and exacerbation of asthma.

PMID- 8549487
TI  - Special susceptibility of the child to certain radiation-induced cancers.
AB  - The carcinogenic effects of exposure to ionizing radiation vary markedly with
      age, as revealed by studies of Japanese atomic bomb survivors and of Marshall
      Islanders exposed to fallout from U.S. nuclear weapons tests in the South Pacific
      in 1954. An increase in cancers of adulthood after intrauterine exposure, as
      reported in 1988, has not been sustained. After childhood exposure, increases in
      leukemia, breast cancer, and thyroid cancer are well established. The
      carcinogenic effects of radiation on the young have been reported after
      intrauterine exposures and after exposures during childhood. Cancers with short
      latent periods such as leukemia occur during childhood, but those with long
      latent periods such as breast cancer occur in adulthood.

PMID- 8549488
TI  - Age-specific carcinogenesis: environmental exposure and susceptibility.
AB  - Environmental exposures in children may occur through many routes, including
      diet, air, and the ingestion of various nonfood items such as medications and
      household materials. This article focuses on dietary exposure, but it does
      highlight the importance of considering other routes of exposure when assessing
      exposure in children. It presents many of the findings in the two recent reports,
      Pesticides in the Diets of Infants and Children and Science and Judgment in Risk
      Assessment of the National Academy of Sciences (NAS)/National Research Council
      (NRC). Diet is an important source of exposure for children to potential
      carcinogens. The trace quantities of chemicals present on or in foodstuffs are
      termed residues. In addition, there are substances that children may be exposed
      to in air and water that should be considered in a total exposure analysis. To
      minimize exposure of the general population to chemical residues in food, water,
      and air, the U.S. government has instituted regulatory controls. These are
      intended to limit exposures to residues while ensuring an abundant and nutritious
      food supply, and safe drinking water and air. The legislative framework for these
      controls was established by the Congress through various local and state laws and
      such federal laws as the Insecticide, Fungicide, and Rodenticide Act (FIFRA), the
      Federal Food, Drug, and Cosmetic Act (FFDCA), the Safe Drinking Water Act (SDWA),
      and the Clean Air Act (CAA). This article summarizes current approaches to
      assessing exposure and susceptibility in children.

PMID- 8549489
TI  - The effects of air pollution on children.
AB  - Air pollutants have been documented to be associated with a wide variety of
      adverse health impacts in children. These include increases in mortality in very
      severe episodes; an increased risk of perineonatal mortality in regions of higher
      pollution, and an increased general rate of mortality in children; increased
      acute respiratory disease morbidity; aggravation of asthma, as shown by increased
      hospital emergency visits or admissions as well as in longitudinal panel studies;
      increased prevalence of respiratory symptoms in children, and infectious episodes
      of longer duration; lowered lung function in children when pollutants increase;
      lowered lung function in more polluted regions; increased sickness rates as
      indicated by kindergarten and school absences; the adverse effects of inhaled
      lead from automobile exhaust. These impacts are especially severe when high
      levels of outdoor pollution (usually from uncontrolled coal burning) are combined
      with high levels of indoor pollution. In developed countries, where indoor
      pollution levels are lower, increasing traffic density and elevated NO2 levels
      with secondary photochemical and fine particulate pollution appear to be the main
      contemporary problem. By virtue of physical activity out of doors when pollution
      levels may be high, children may experience higher exposures than adults. Air
      pollution is likely to have a greater impact on asthmatic children if they are
      without access to routine medical care.

PMID- 8549490
TI  - Indoor air pollution and childhood asthma: effective environmental interventions.
AB  - Exposure to indoor air pollutants such as tobacco smoke and dust mites may
      exacerbate childhood asthma. Environmental interventions to reduce exposures to
      these pollutants can help prevent exacerbations of the disease. Among the most
      important interventions is the elimination of environmental tobacco smoke from
      the environments of children with asthma. However, the effectiveness of reducing
      asthmatic children's exposure to environmental tobacco smoke on the severity of
      their symptoms has not yet been systematically evaluated. Dust mite reduction is
      another helpful environmental intervention. This can be achieved by enclosing the
      child's mattresses, blankets, and pillows in zippered polyurethane-coated
      casings. Primary prevention of asthma is not as well understood. It is
      anticipated that efforts to reduce smoking during pregnancy could reduce the
      incidence of asthma in children. European studies have suggested that reducing
      exposure to food and house dust mite antigens during lactation and for the first
      12 months of life diminishes the development of allergic disorders in infants
      with high total IgE in the cord blood and a family history of atopy. Many
      children with asthma and their families are not receiving adequate counseling
      about environmental interventions from health care providers or other sources.

PMID- 8549491
TI  - Environmental risk factors of childhood asthma in urban centers.
AB  - Asthma morbidity and mortality are disproportionately high in urban centers, and
      minority children are especially vulnerable. Factors that contribute to this
      dilemma include inadequate preventive medical care for asthma management,
      inadequate asthma knowledge and management skills among children and their
      families, psychosocial factors, and environmental exposure to allergens or
      irritants. Living in substandard housing often constitutes excess exposure to
      indoor allergens and pollutants. Allergens associated with dust mites (DM) and
      cockroaches (CR) are probably important in both onset and worsening of asthma
      symptoms for children who are chronically exposed to these agents. Young children
      spend a great deal of time on or near the floor where these allergens are
      concentrated in dust. Of children (2 to 10 years of age) living in metropolitan
      Washington, DC, 60% were found to be sensitive to CR and 72% were allergic to DM.
      Exposure to tobacco smoke contributes to onset of asthma earlier in life and is a
      risk factor for asthma morbidity. Since disparity of asthma mortality and
      morbidity among minority children in urban centers is closely linked to
      socioeconomic status and poverty, measures to reduce exposure to environmental
      allergens and irritants and to eliminate barriers to access to health care are
      likely to have a major positive impact. Interventions for children in urban
      centers must focus on prevention of asthma symptoms and promotion of wellness.

PMID- 8549492
TI  - The youth role in creating a healthy future for the earth: an examination of the
      link between collective action for the environment and the emotional health of
      children.

PMID- 8549493
TI  - Creating a healthy home: environmental building materials--what are they? Where
      are they?

PMID- 8549494
TI  - How are children different from adults?
AB  - Several factors alter an individual's risk for an environmentally related
      illness. A major determinant is the age of the individual. The toxicodynamic
      processes that determine exposure, absorption, metabolism, excretion, and tissue
      vulnerability are all age related. This paper discusses each of these processes
      and their variability with age, and illustrates these points with examples of
      environmentally related disease cases.

PMID- 8549495
TI  - Building healthy communities for children: the transportation link.

PMID- 8549496
TI  - Developing brain as a target of toxicity.
AB  - The human brain forms over an unusually long period compared to other organs.
      While most of the basic structure is laid down before birth, neuron proliferation
      and migration continue in the postnatal period. The blood-brain barrier is not
      fully developed until the middle of the first year of life. The number of
      synaptic connections between neurons reaches a peak around age two and is then
      trimmed back by about half. Similarly, there is great postnatal activity in the
      development of receptors and transmitter systems as well as in the production of
      myelin. Many of the toxic agents known to damage the developing brain interfere
      with one or more of these developmental processes. Those with antimitotic action,
      such as X-ray and methyl mercury, have distinctly different effects on structure
      depending on which neurons are forming at the time of exposure. Vulnerability to
      agents that interfere with cell production decreases rapidly over the early
      postnatal period. Other toxic substances, such as psychoactive drugs and agents
      that alter hormone levels, are especially hazardous during synaptogenesis and the
      development of transmitter systems, and thus continue to be damaging for years
      after birth. Still other toxic substances such as lead, seem to have their
      greatest effects during even later stages of brain development, perhaps by
      interfering with the trimming back of connections. Guidelines designed to protect
      human populations from developmental neurotoxicity need to take into account the
      changing sensitivity of the brain as it passes through different developmental
      stages, as well as the fundamental differences in the effects of toxicants on the
      mature and the developing brain.

PMID- 8549497
TI  - Behavioral toxicology.
AB  - The new fields of behavioral toxicology and behavioral teratology investigate the
      outcome of specific toxic exposures in humans and animals on learning, memory,
      and behavioral characteristics. Three important classes of behavioral
      neurotoxicants are metals, solvents, and pesticides. The clearest data on the
      deleterious effects of prenatal exposure to toxicants comes from the study of two
      metals, lead and mercury, and from epidemiological investigations of the effects
      of alcohol taken during pregnancy. Less complete data are available for two other
      groups of agents, solvents and pesticides. What we do know about their effects on
      the fetal brain is convincing enough to make us demand caution in their
      distribution.

PMID- 8549498
TI  - Pesticides--how research has succeeded and failed to translate science into
      policy: endocrinological effects on wildlife.
AB  - Toxicological research became institutionalized in the United States in response
      to society's concern about cancer and acute mortality. Driven by risk assessment,
      research focused on the need for data development and the standardization of
      testing for regulatory and management purposes in a reactive mode. Although the
      research community has provided evidence for over 40 years that a number of
      pesticides and industrial chemicals have disruptive effects on the endocrine
      system, little attention was given to the evidence when determining the health
      hazards of synthetic chemicals because of the fixation on cancer. However, recent
      findings concerning the effects of a number of widespread chemicals on the
      reproductive success and fertility of wildlife and humans has led to the call for
      a proactive approach using investigative research (forensic science). Suggestions
      are presented to modernize the research agenda of public health institutions to
      meet society's needs to address the problems of exposure to endocrine, nervous,
      and immune system disruptors.

PMID- 8549499
TI  - Pesticides--how research has succeeded and failed in informing policy: DDT and
      the link with breast cancer.
AB  - Investigation of chemical exposures as possible etiologic factors for breast
      cancer has not been a research priority in the United States, which is surprising
      given the evidence from animal studies that environmental chemicals cause cancer
      and reproductive dysfunction. Study of environmental chemicals has also been
      indicated by the failure of traditional epidemiologic methods to account for
      significant proportions of breast cancer incidence with other risk factors. The
      fact that breast cancer risk is strongly associated with reproductive hormones is
      a further clue that environmental chemicals should be investigated. In addition
      to cancer, specific outcomes that need to be explored are reproductive
      dysfunction, immunotoxicity and neurotoxicity. Policy guiding our research should
      encourage toxicologic investigations of exposures to environmental chemicals that
      use state-of-the-art methods to determine exposure and human health effects.
      Using the approach suggested by John McLachlan, functional toxicology should be
      used to assess the activity of chemicals with regard to these outcomes. Just as
      dioxin toxicity can be expressed as toxic equivalents, estrogenic activity, for
      example, can be characterized in terms of estrogenic equivalents. In addition to
      the need to undertake this kind of research, needs for methods development and
      creative research funding mechanisms are discussed. Prevention of breast cancer
      may require intervention at an early age. Better understanding of breast cancer
      etiology, and especially its environmental components, may lead us toward that
      goal.

PMID- 8549500
TI  - Elevated incidence of childhood leukemia in Woburn, Massachusetts: NIEHS
      Superfund Basic Research Program searches for causes.
AB  - Between 1966 and 1986, the childhood leukemia rate in Woburn, Massachusetts, was
      4-fold higher than the national average. A multidisciplinary research team from
      MIT, which is being supported by the NIEHS Superfund Basic Research Program, has
      explored the possible importance of a temporal correlation between the period of
      elevated leukemia and a previously unrecognized mobilization of toxic metals from
      a waste disposal site in north Woburn. Residents of Woburn may have been exposed
      to arsenic (70 micrograms/l) and chromium (240 micrograms/l) at levels in excess
      of federal drinking water standards (50 micrograms/l for each metal) by consuming
      municipal groundwater contaminated with these metals. Research is currently
      underway a) to elucidate the mechanisms and the pathways by which these metals
      were transported from the waste disposal site to the drinking water supply; b) to
      determine the identity of the principal human cell mutagens in samples of aquifer
      materials collected from the site of the municipal supply wells; and c) to
      measure the extent of exposure and genetic change in residents who consumed the
      contaminated well water.

PMID- 8549502
TI  - Topics in Dietary Fibre Research. Proceedings of an International Symposium.
      Rome, Italy, 5-7 May 1992.

PMID- 8549501
TI  - Biomarkers and pediatric environmental health.
AB  - It is now possible to identify biochemical and/or cellular changes in humans due
      to exposure to an environmental toxin. These changes are called biomarkers and
      are currently used in research studies to identify individuals exposed to
      specific toxic substances. Advances in the field of biomarker technology may have
      important implications for the detection, prevention, and treatment of certain
      diseases in children. This technology may enable physicians to screen children
      who have no clinically detectable illness for evidence of exposure to specific
      toxins. Such information could lead to implementation of preventive measures and
      development of new therapeutic strategies. However, several important issues,
      including potential adverse consequences resulting from the widespread use of
      this technology, must be considered prior to its utilization within a clinical
      setting. Leaders of the pediatric and public health communities should recognize
      the paucity of scientific data in the pediatric environmental health area, and
      new approaches to this important aspect of child health should be developed. This
      article will address several of the issues involved in pediatric environmental
      health and consider questions that should be answered as the potential for
      technology transfer becomes a reality.

PMID- 8549503
TI  - Colorectal cancer and intake of dietary fibre. A summary of the epidemiological
      evidence.

PMID- 8549504
TI  - Dietary fibre and plasma lipids.

PMID- 8549505
TI  - Dietary fibre in the treatment of metabolic diseases.

PMID- 8549506
TI  - In vitro binding properties of dietary fibre.

PMID- 8549507
TI  - Bioavailability of micronutrients in a fibre-rich diet, especially related to
      minerals.

PMID- 8549508
TI  - Dietary fibre and drug interactions.

PMID- 8549509
TI  - Enzymatic treatments for the production of modified dietary fibre.

PMID- 8549510
TI  - Evaluation of a fibre intake questionnaire using weighed records.

PMID- 8549511
TI  - A study to investigate the relationship between dietary fibre intake and
      gastrointestinal diseases.

PMID- 8549512
TI  - Inulin, an alternative dietary fibre. Properties and quantitative analysis.

PMID- 8549513
TI  - Determination of total, soluble and insoluble dietary fibre: collaborative study.

PMID- 8549514
TI  - Dietary fibre analysis: methodological error sources.

PMID- 8549515
TI  - Mode of action of oat bran in the gastrointestinal tract.

PMID- 8549516
TI  - Influence of non-starch polysaccharides on gastrointestinal endocrine mechanisms.

PMID- 8549518
TI  - Dietary fibre and the gastrointestinal tract: differing trophic effects on muscle
      and mucosa of the stomach, small intestine and colon.

PMID- 8549517
TI  - Suggested sterol-binding mechanisms of dietary fibre based on ileostomy studies.

PMID- 8549519
TI  - Short-chain fatty acids and colorectal cancer.

PMID- 8549520
TI  - Effect of finely ground wheat bran or spelt chaff on the transit time in pigs.

PMID- 8549521
TI  - Relationships between the composition of dietary fibre in the diet and the
      digestion and transit time in rats.

PMID- 8549522
TI  - Effect of konjac fibre (glucomannan) on glucose and lipids.

PMID- 8549523
TI  - Clinical effects of a dietary fibre supplement. A review.

PMID- 8549524
TI  - Antihypertensive activity of a vegetable fibre preparation: a preliminary, double
      blind, placebo-controlled study.

PMID- 8549525
TI  - The degradation of phytic acid in legumes prepared by different methods.

PMID- 8549526
TI  - Possible common properties of dietary fibre constituents and polyphenols.

PMID- 8549527
TI  - Effects of processing on dietary fibre in vegetables.

PMID- 8549528
TI  - Dietary fibre intake: trends in Italy.

PMID- 8549529
TI  - The diet as a source of dietary fibre.

PMID- 8549530
TI  - Study of the dietary fibre content in cocoa.

PMID- 8549531
TI  - Dietary fibre in olives. Characterisation of fractions.

PMID- 8549532
TI  - A comparison of commercial fibre sources: barley bran, corn bran, orange fibre
      and sugar beet fibre.

PMID- 8549533
TI  - X-ray and enzymic studies on amorphous cellulose of the Macroalga ulva.

PMID- 8549534
TI  - Formation of short-chain fatty acids from different dietary fibre sources in the
      rat caecum.

PMID- 8549535
TI  - Interactions between large intestine fermentation and dietary calcium.

PMID- 8549536
TI  - The role of fibre in the treatment of secondary hyperlipidaemia in nephrotic
      patients.

PMID- 8549537
TI  - Metabolic effects of hypocaloric high-carbohydrate/high-fibre diet in non-insulin
      dependent diabetic patients.

PMID- 8549538
TI  - The effect of liquid fibre on feeding behaviour.

PMID- 8549539
TI  - Binding of calcium by brans under simulated gastrointestinal pH conditions. In
      vitro study with 45Ca.

PMID- 8549540
TI  - Modification of dietary fibre content in different kinds of bread.

PMID- 8549541
TI  - Effects of freezing preservation on dietary fibre content of mango (Mangifera
      indica L.) fruit.

PMID- 8549542
TI  - Dietary fibre in pineapple fruit.

PMID- 8549543
TI  - Dietary fibre, resistant starch and in vitro starch digestibility of cereal
      meals. Glycaemic and insulinaemic responses in NIDDM patients.

PMID- 8549544
TI  - Effects of processing on dietary fibre content of asparagus.

PMID- 8549545
TI  - Cell-wall chemistry and architecture in relation to sources of dietary fibre.

PMID- 8549546
TI  - Influence of thermal processes on dietary fibre: a study on turnip (Brassica
      napus).

PMID- 8549547
TI  - Dietary fibre in Spanish kiwifruit.

PMID- 8549548
TI  - Neutral detergent fibre and pectic substances in pineapple and its derivates:
      juices and nectars.

PMID- 8549549
TI  - The effects of high intakes of fibre ingested at breakfast on satiety.

PMID- 8549550
TI  - Content of dietary fibre in the total daily diets of hospitalised children.

PMID- 8549551
TI  - Chemical and physiological aspects of enzyme-modified fibre.

PMID- 8549553
TI  - Dietary fibre in legumes: effect of processing.

PMID- 8549552
TI  - Analytic method for determination of inulin in yoghurt enriched with soluble
      fiber.

PMID- 8549554
TI  - Effect of ripening on resistant starch and total sugars in Musa paradisiaca
      sapientum: glycaemic and insulinaemic responses in normal subjects and NIDDM
      patients.

PMID- 8549555
TI  - Dietary fibre: effect of processing and nutrient interactions.

PMID- 8549556
TI  - The effects of high-fibre cereal-based breakfast meals on daily dietary intakes
      and bowel function.

PMID- 8549557
TI  - Lipoprotein metabolism, cellular model and dietary fibre.

PMID- 8549558
TI  - Effects of oat bran concentrate on rat serum lipids and liver fat infiltration.

PMID- 8549559
TI  - Effect of dietary fibre on weight correction after modified fasting.

PMID- 8549561
TI  - Definition and measurement of dietary fibre.

PMID- 8549560
TI  - Dietary fibre analysis--an overview.

PMID- 8549562
TI  - Dietary fibre intakes in Europe: overview and summary of European research
      activities, conducted by members of the Management Committee of COST 92.

PMID- 8549563
TI  - Physical properties of polysaccharides in food.

PMID- 8549564
TI  - Effect of reduced rate of carbohydrate absorption on carbohydrate and lipid
      metabolism.

PMID- 8549565
TI  - Role of gastrointestinal motility in the delay of absorption by dietary fibre.

PMID- 8549566
TI  - In vitro studies to predict physiological effects of dietary fibre.

PMID- 8549567
TI  - The impact of complex carbohydrates on energy balance.

PMID- 8549568
TI  - Methods to assess glucose metabolism in humans in relation to carbohydrate and
      fibre in the diet.

PMID- 8549569
TI  - The role of pulmonary CO2 flow in the control of the phase I ventilatory response
      to exercise in humans.
AB  - To gain an insight into the origin of the phase I ventilatory response to
      exercise (ph I) in humans, pulmonary ventilation (VE) and end-tidal partial
      pressures of oxygen and carbon dioxide (PETO2 and PETCO2, respectively) were
      measured breath-by-breath in six male subjects during constant-intensity exercise
      on the cycle ergometer at 50, 100 and 150 W, with eupnoeic normocapnia (N) or
      hyperpnoeic hypocapnia (H) established prior to the exercise test. Cardiac output
      (Qc) was also determined beat-by-beat by impedance cardiography on eight subjects
      during moderate exercise (50 W), and the CO2 flow to the lungs (Qc.Cv-CO2 where
      Cv-CO2 is concentration of CO2 in mixed veneous blood) was estimated with a time
      resolution of one breathing cycle. In N, the initial abrupt increase of VE during
      ph I (delta VE approximately 18 1.min-1 above rest) was followed by a transient
      fall. When PETCO2 started to increase (and PETO2 decreased) VE increased again
      (phase II ventilatory response, ph II). In H, during ph I delta VE was similar to
      that of N. By contrast, during ph II delta VE kept gradually decreasing and
      started to increase only when PETCO2 had returned to approximately 40 mmHg (5.3
      kPa). Thus, as a result of the prevailing initial conditions (N or H) a temporal
      shift of the time-course of VE during ph II became apparent. No correlation was
      found between CO2 flow to the lungs and VE during ph I. These results are
      interpreted as suggesting that an increased CO2 flow to the lungs does not
      constitute an important factor for the initial hyperventilatory response to
      exercise. They are rather compatible with a neural origin of ph I, and would
      support the "neurohumoral" theory of ventilatory control during exercise.

PMID- 8549570
TI  - The comparison of peak oxygen uptake between swim-bench exercise and arm stroke.
AB  - To compare maximal cardio-respiratory stress between swim-bench exercise (SB) and
      arm stroke (AS), peak oxygen uptake (VO2peak) was measured in six trained
      swimmers. The SB was performed at stroke frequency of 50.min-1. Oxygen uptake
      (VO2) was measured during exercise at 3-min constant exercise intensities in SB
      and at 4-min constant water flow rates in AS. We measured a steady-state VO2
      within 3 or 4 min after the beginning of each exercise. The exercise intensity or
      the water flow rate was increased by 14.7 W or by 0.05 m.s-1, respectively, until
      a levelling-off of VO2 was observed. The VO2 was measured by the Douglas bag
      method. Heart rate (HR) and blood lactate concentration ([la-]b) were determined
      at the exercise intensity and the water flow rate at which VO2peak was obtained.
      At submaximal levels, VO2 increased in proportion to exercise intensity for SB
      and to the water flow rate for AS. A levelling-off of VO2 was observed in all
      subjects for both kinds of exercise. The VO2peak during SB [2.13 (SD 0.25)1.min
      1] was significantly lower than that during AS [2.72 (SD 0.39)1.min-1] and
      corresponded to 78.9 (SD 7.0)% of AS VO2peak. Maximal HR during SB was also
      significantly lower than that during AS. No significant differences between SB
      and AS were found for either pulmonary ventilation or [la-]b. The peak exercise
      duration in SB [2.4 (SD 0.5) min] was significantly shorter than that in As [3.6
      (SD 0.5) min]. These results would suggest that even though both kinds of
      exercise use the muscles of the upper body, active muscle groups involved during
      SB are different and/or smaller, and maximal stress on the cardio-respiratory
      system is lower when compared to AS.

PMID- 8549571
TI  - The relationship between voluntary electromyogram, endurance time and intensity
      of effort in isometric handgrip exercise.
AB  - The relationship between relative force, electromyogram (EMG) and time to fatigue
      was examined in seven male and seven female subjects [mean (SD) age, 21.7 (3.2)
      years] during isometric handgrip exercise. Subjects performed sustained
      submaximal contractions of the right handgrip at three different intensities:
      30%, 50%, and 75% of the pretrial maximum voluntary contraction (MVC). EMG was
      sampled in 1-s epochs every 15 s during the contractions, and the integrated EMG
      (IEMG) values were then normalized to that of the pretrial MVC. As expected, time
      to fatigue was longest at 30% MVC and shortest at 75% MVC, but women performed
      consistently longer than men at each of the three intensities [woman vs men;
      400.7 (35.8) vs 364.3 (34.4) s, 205.1 (15.6) vs 139.4 (13) s, and 89.9 (11.4) vs
      66.4 (6.4) s, for 30%, 50%, and 75% MVC, respectively; P < 0.05)]. IEMG increased
      in a non-linear fashion over time during each trial, with the magnitude of IEMG
      being proportional to the intensity of the contraction. At the endurance limit,
      IEMG was greatest in the 75% MVC trial, however, no IEMG values reached those
      obtained in the related MVC [30%, 57.2 (6.9)%, 50%, 84.6 (5.7)%; 75%, 92.8
      (7.4)%]. In conclusion, endurance time during sustained submaximal isometric
      handgrip exercise is dependent up on the intensity of the effort, with women
      having significantly larger endurance times than men. The related increase in
      IEMG is also proportional to the intensity of effort, however, the factors
      causing force to fail prior to the final IEMG reaching its predicted maximum
      remain to be elucidated.

PMID- 8549573
TI  - Sodium intake and post-exercise rehydration in man.
AB  - This study examined the effect of the sodium content of drinks on the rehydration
      process after exercise. Six healthy male volunteers were dehydrated by a mean
      (SEM) of 1.9(0.0) % of body mass by intermittent cycle exercise in a warm (32
      degrees C), humid (54% RH) environment. Subjects exercised on four occasions at
      weekly intervals with each trial beginning in the morning, 3 h after a standard
      breakfast. Over a 30-min period beginning 30 min after the end of exercise,
      subjects ingested one of the four test drinks in a volume equivalent to 1.5 times
      their body mass loss. Drink composition was constant except for the sodium (and
      matching anion) content. Sodium content of drinks A, B, C and D was 2, 26, 52 and
      100 mmol.l-1, respectively. Treatment order was randomised using a four-way
      crossover incomplete block design. Blood and urine samples were obtained before
      exercise, immediately before and after the rehydration period and at 0.5, 1.5,
      3.5 and 5.5 h after the end of the rehydration period. Data were analysed by
      parametric or non-parametric statistical tests are appropriate. The volume of
      fluid consumed was the same on all trials [2045(45) ml]. From the 1.5-h sample
      onwards, a significant treatment effect on cumulative urine output was apparent,
      with the volume excreted being inversely related to the sodium content of the
      drink consumed. By the end of the trial, subjects were in net negative fluid
      balance on trials A [by 689(124) ml] and B [by 359(87) ml]; on trials C [-2(79)
      ml] and D [+98(67) ml], subjects were approximately euhydrated. Cumulative
      urinary sodium output was higher on treatment D than on the other trials after
      5.5 h. Plasma volume was lower after exercise than before; on trials B, C and D,
      plasma volume was higher than the pre-exercise value from 0.5 h after the end of
      the rehydration period onwards. On trial A, plasma volume was higher than the pre
      exercise value at 3.5 and 5.5 h after the end of the rehydration period. At 1.5 h
      after the end of the rehydration period, the increase in plasma volume was
      greater on trials C and D than on trial A. These results suggest that the
      fraction of the ingested fluid that was retained was directly related to the
      sodium concentration.

PMID- 8549572
TI  - Post-exercise gastric emptying of carbohydrate solutions determined using the 13C
      acetate breath test.
AB  - In an attempt to measure gastric emptying of carbohydrate solutions after
      exercise, we used the 13C acetate breath test to differentiate the gastric
      emptying of three approximately isoenergetic carbohydrate solutions (i.e.
      glucose, glucose polymer and sucrose) from each other and from water. On four
      separate occasions, six post-absorptive subjects walked on an inclined treadmill
      at 70% maximum oxygen uptake for 1 h and were then given 330 ml of one of the
      solutions in which 150 mg of sodium 1-[13C] acetate had been dissolved. Breath
      samples were collected at regular (2-30 min) intervals over the next 3.5 h for
      analysis of expired 13CO2 by isotope ratio mass spectrometry. When water was
      given, all subjects reached peak breath enrichment after 30 min, and had a mean
      (SE) gastric emptying time of 33.2 (1.6) min. Peak breath enrichment occurred
      later for sucrose and glucose polymer at 54.3 (3.1) min and 59.0 (2.1) min
      respectively (P < 0.01), and for glucose this was even later, at 62.3 (1.0) min
      (P < 0.05). Calculated gastric emptying times for sucrose and glucose polymer
      were almost identical [66.5 (2.5) and 69.8 (2.9) min respectively], whereas that
      for glucose was significantly slower [76.8 (3.2) min; P < 0.02], probably
      reflecting the effects of increased osmolality. The gastric emptying of all
      carbohydrates were significantly longer than for water (P < 0.01). These results
      show that in the post-exercise state the 13C acetate breath test can be used to
      differentiate the gastric emptying rates of water and carbohydrate solutions of
      different properties.

PMID- 8549574
TI  - Dynamics of anaerobic and aerobic energy supplies during sustained high intensity
      exercise on cycle ergometer.
AB  - Eight male subjects were examined for the transition from anaerobic to aerobic
      energy supplies during supramaximal pedalling for 120 s on a cycle ergometer. The
      O2 debt and O2 deficit were measured for anaerobic supply, while O2 intake during
      exercise was measured for aerobic supply. The lactic acid system was also
      observed through postexercise peak blood lactate concentration [la-]b,peak. Since
      a continuous observation of O2 debt and [la-]b,peak during a single period of
      pedalling is not possible, pedalling of seven varying durations (5, 15, 30, 45,
      60, 90 and 120 s) were repeated. Mechanical power output reached its peak
      immediately after the beginning of exercise, then rapidly declined, becoming
      gradual after 60 s. The O2 debt and O2 deficit were highest immediately after the
      beginning of exercise, then rapidly decreased to nil in 60 s. The O2 intake was
      small at the beginning, then rapidly increased to attain a steady state in 30 s
      at 80%-90% of the maximal O2 intake of the subject. Energy supply from the lactic
      acid system indicated by the increment in [la-]b,peak reached its highest value
      during the period between 5 and 15 s, then rapidly decreased to nil in 60 s. The
      results would suggest that anaerobic supply was the principal contributor during
      the initial stage of exercise, but that aerobic supply gradually took over. In 60
      s anaerobic supply ceased, and aerobic supply became the principal contributor.
      The cessation of anaerobic energy supply took place much sooner than the 2 min
      that is conventionally suggested.

PMID- 8549575
TI  - Does the threshold of transcutaneous partial pressure of carbon dioxide represent
      the respiratory compensation point or anaerobic threshold?
AB  - On reaching the respiratory compensation point (RCP) during rapidly increasing
      incremental exercise, the ratio of minute ventilation (VE) to CO2 output (VCO2)
      rises, which coincides with changes of arterial partial pressure of carbon
      dioxide (PaCO2). Since PaCO2 changes can be monitored by transcutaneous partial
      pressure of carbon dioxide (PCO2,tc) RCP may be estimated by PCO2,tc measurement.
      Few available studies, however, have dealt with comparisons between PCO2,tc
      threshold (TAT) and lactic, ventilatory or gas exchange threshold (VAT), and the
      results have been conflicting. This study was designed to examine whether this
      threshold represents RCP rather than VAT. A group of 11 male athletes performed
      incremental exercise (25 W.min-1) on a cycle ergometer. The PCO2,tc at (44
      degrees C) was continuously measured. Gas exchange was computed breath-by-breath
      and hyperaemized capillary blood for lactate concentration ([la-]b) and PaCO2
      measurements was sampled each 2 min. The TAT was determined at the deflection
      point of PCO2,tc curve where PCO2,tc began to decrease continuously. The VAT and
      RCP were evaluated with VCO2 compared with oxygen uptake (VO2) and VE compared
      with the VCO2 method, respectively. The PCO2,tc correlated with PaCO2 and end
      tidal PCO2. At TAT, power output [P, 294 (SD 40) W], VO2 [4.18 (SD 0.57) l.min.1]
      and [la(-)] [4.40 (SD 0.64) mmol.l-1] were significantly higher than those at
      VAT[P 242 (SD 26) W, VO2 3.56 (SD 0.53) l.min-1 and [la(-)]b 3.52 (SD 0.75),
      mmol.l-1 respectively], but close to those at RCP [P 289 (SD 37) W; VO2 3.97 (SD
      0.43) l.min-1 and [la(-)]b 4.19 (SD 0.62) mmol.l-1, respectively]. Accordingly,
      linear correlation and regression analyses showed that P, VO2 and [la(-)]b at TAT
      were closer to those at RCP than at VAT. In conclusion, the TAT reflected the RCP
      rather than VAT during rapidly increasing incremental exercise.

PMID- 8549576
TI  - The role of metabolites in strength training. I. A comparison of eccentric and
      concentric contractions.
AB  - This study examined the role of high forces versus metabolic cost in the
      adaptations following strength training. Ten young, healthy male and female
      subjects trained one leg using concentric (CL) and the other using eccentric (EL)
      contractions of the quadriceps muscle for 20 weeks. EL used weights which were
      35% higher than those used for CL. Isometric strength, and the length:tension and
      force:velocity relationship of the muscle were measured before and after
      training. Muscle cross-sectional area (CSA) was measured near the knee and hip
      using computed tomography. Increases in isometric strength were greater for CL
      compared to EL, the difference being significant with the knee at 1.57 rad (90
      degrees) [mean (SD), 43.7 (19.6)% vs 22.9 (9.8)%, respectively; P = 0.01].
      Increases in isokinetic strength tended to be larger for EL, although the
      differences were not significant. Significant increases in CSA occurred near the
      hip for both EL and CL. These results suggest that metabolic cost, and not high
      forces alone, are involved in the stimuli for muscle hypertrophy and strength
      gains following high-resistance training.

PMID- 8549577
TI  - The role of metabolites in strength training. II. Short versus long isometric
      contractions.
AB  - The role of intramuscular metabolite changes in the adaptations following
      isometric strength training was examined by comparing the effect of short,
      intermittent contractions (IC) and longer, continuous (CC) contractions. In a
      parallel study, the changes in phosphate metabolites and pH were examined during
      the two protocols using whole-body nuclear magnetic resonance spectroscopy
      (NMRS). Seven subjects trained three time per week for 14 weeks. The right leg
      was trained using four sets of ten contractions, each lasting 3 s with a 2-s rest
      period between each contraction and 2 min between each set. The left leg was
      trained using four 30-s contractions with a 1-min rest period between each. Both
      protocols involved isometric contractions at 70% of a maximum voluntary isometric
      contraction (MVC). The MVC, length:tension and force:velocity relationships and
      cross-sectional area (CSA) of each leg were measured before and after training.
      The increase in isometric strength was significantly greater (P = 0.041) for the
      CC leg (median 54.7%; P = 0.022) than for IC (31.5%; P = 0.022). There were no
      significant differences between the two protocols for changes in the
      length:tension or force:velocity relationships. There were significant increases
      in muscle CSA for the CC leg only. NMRS demonstrated that the changes in
      phosphate metabolites and pH were greater for the CC protocol. These findings
      suggest that factors related to the greater metabolite changes during CC training
      results in greater increases in isometric strength and muscle CSA.

PMID- 8549578
TI  - Muscle strength during bedrest with and without muscle exercise as a
      countermeasure.
AB  - Bedrest is known to be a useful experimental model for simulating weightlessness
      and studying its effects on human skeletal muscle activity. We therefore
      conducted a study in which 12 healthy male subjects underwent 28 days of
      continuous exposure to 6 degrees head-down bedrest. Our main objective was to
      test a set of preventive countermeasures for maintaining the stability of the
      human body. Of the subjects 6 performed deadlifts in the supine position for 30
      to 45 min each day. The isometric actions were performed for 5-30 s at 90, 120
      and 150 degrees knee angles and isokinetic training at speeds of 30 and 180
      degrees.s-1. In vivo quadriceps muscle strength was measured under controlled
      experimental conditions with a commercial dynamometer. The hypothesis that
      intense daily isometric and isokinetic leg exercise and lower body negative
      pressure (LBNP) might serve to maintain muscle strength under conditions of
      weightlessness was tested. Of the subjects 6, who did not perform any exercise,
      served as the control population under conditions of simulated weightlessness.
      The results showed that a significant reduction (P < or = 0.0001) in the muscle
      force [-10.3 (SD 6.7%)] occurred in the control group whereas no significant
      changes were observed in the trained group [+3.9 (6.8%)]. From these studies we
      conclude that intense muscle training and LBNP constitute efficient
      countermeasures to compensate for the biomechanical effects of weightlessness on
      human lower limbs and to limit other factors such as cardiovascular
      deconditioning.

PMID- 8549579
TI  - Non-invasive prediction of blood lactate response to constant power outputs from
      incremental exercise tests.
AB  - We determined the ability of gas exchange analyses during incremental exercise
      tests (IXT) to predict blood lactate levels associated with a range of constant
      power output cycle ergometer tests. Twenty-seven healthy young men performed
      duplicate IXT and four 15-min constant power output tests at intensities ranging
      from moderate to very severe, before and after a training program. End-exercise
      blood lactate levels were approximated from superficial venous samples obtained
      60 s after each constant power output test. From IXT, the power outputs
      corresponding to peak oxygen uptake (Wmax) and lactic acidosis threshold (WLAT),
      were determined. We examined the ability of four measures of exercise intensity
      to predict blood lactate levels for power outputs above the LAT: (1) power output
      (W), (2) power difference (W-WLAT), (3) power fraction (W/Wmax) and (4) power
      difference to delta ratio [(W-WLAT)/(Wmax-WLAT)]. Correlation coefficients were r
      = 0.38, 0.69, 0.75, and 0.81, respectively. The best linear regression prediction
      equation was: lactate (mmol.l-1) = 12.2[(W-WLAT)/(Wmax-WLAT)] + 0.7 mmol.l-1.
      This relationship was not significantly affected by training, despite increased
      values of LAT and peak oxygen uptake. Normalizing exercise intensity to the range
      of power outputs between WLAT and Wmax provided an estimate of blood lactate
      response to constant power outputs with a standard error of the estimate of 1.66
      mmol.l-1.

PMID- 8549580
TI  - Energy cost and energy sources in karate.
AB  - Energy costs and energy sources in karate (wado style) were studied in eight male
      practitioners (age 23.8 years, mass 72.3 kg, maximal oxygen consumption (VO2max)
      36.8 ml.min-1.kg-1) performing six katas (formal, organized movement sequences)
      of increasing duration (from approximately 10 s to approximately 80 s). Oxygen
      consumption (VO2) was determined during pre-exercise rest, the exercise period
      and the first 270 s of recovery in five consecutive expired gas collections. A
      blood sample for lactate (la-) analysis was taken 5 min after the end of
      exercise. The overall amount of O2 consumed during the exercise and in the
      following recovery increased linearly with the duration of exercise (t) from
      approximately 1.51 (for t equal to 10.5 s (SD 1.6)) to approximately 5.8 l, for t
      equal to 81.5 s (SD 1.0). The energy release from la- production (VO2la-)
      calculated assuming that an increase of 1 mmol.l-1 la- corresponded to a VO2 of 3
      mlO2.kg-1 was negligible for t equal to or less than 20 s and increased to 17.3
      ml.kg-1 (la- = 5.8 mmol.l-1 above resting values) for t equal approximately to 80
      s. The overall energy requirement (VO2eq) as given by the sum of VO2 and VO2la-
      was described by VO2eq = 0.87 + 0.071.t (n = 64; r2 = 0.91), where VO2eq is in
      litres and t in seconds. This equation shows that the metabolic power (VO2eq.t-1)
      for this karate style is very high: from approximately 9.5 l.min-1 for t equal to
      10 s to approximately 4.9 l.min-1 for t equal to 80 s, i.e. from 3.5 to 1.8 times
      the subjects' VO2max. The fraction of VO2eq derived from the amount of O2
      consumed during the exercise increased from 11% for t equal to 10 s to 41% for t
      equal to 80 s whereas VO2la- was negligible for t equal to or less than 20 s and
      increased to 13% for t equal to 80 s. The remaining fraction (from 90% for t
      equal to 10 s to 46% for t equal to 80 s), corresponding to the amount of O2
      consumed in the recovery after exercise, is derived from anaerobic alactic
      sources, i.e. from net splitting of high energy phosphates during the exercise.

PMID- 8549581
TI  - Sodium citrate ingestion and muscle performance in acute hypobaric hypoxia.
AB  - Eight subjects were studied on four occasions following ingestion of a 300-ml
      solution containing either sodium citrate (C, 0.4 g.kg-1 body mass) or placebo
      (P, sodium chloride 0.045 g.kg-1 body mass), at local barometric pressure (N, PB
      approximately 740 mmHg, 98.7 kPa) or hypobaric hypoxia (HH, PB = 463 mmHg, 61.7
      kPa). At 2 h after ingestion of the solution, the subjects performed prolonged
      isometric knee-extension at 35% of the maximal voluntary contraction (MVC)
      measured either in N or HH. Results showed that ingestion of C led to an
      improvement in muscle endurance (P < 0.01). However, this increase in endurance
      time for knee extensor muscles was only significant in N (+22%, P < 0.05,
      compared to +15%, NS, at N and HH, respectively). Following ingestion of sodium
      citrate, pre-exercise bicarbonate concentrations and pH levels were significantly
      higher than those measured after P ingestion. A significant treatment effect was
      observed for blood lactate concentrations with values higher for C than for P
      after 4, 6 and 10 min of recovery (P < 0.05). Electromyographic signals (EMG)
      were obtained from the vastus lateralis muscle during the prolonged isometric
      contraction at 35% MVC. The mean power frequency (MPF) significantly decreased in
      time under both N-P and N-C conditions. In HH, no significant decrease in MPF was
      observed with time. The results suggest that C ingestion was an ergogenic aid
      enhancing endurance during a sustained isometric contraction. In addition, it is
      suggested that fatigue during prolonged isometric contraction in HH was not
      directly related to factors determining the EMG signs of fatigue.

PMID- 8549582
TI  - Cardiac responses to maximal anisotonic isometric contractions during handgrip
      and leg extension.
AB  - A group of 14-healthy men performed anisotonic isometric contractions (AIC), for
      60 s, at an intensity of 100% maximal voluntary contraction force (MVC) during
      handgrip (HG) and leg extension (LE). Heart rate (fc), stroke volume index (SVI)
      and cardiac output index (QcI) were measured during the last 10 s of both AIC by
      an impedance reography method. Force (F) exerted by the subjects was recorded
      continuously and reported as a relative force (Fr) (% MVC). The F generated
      during MVC was greater for LE than for HG (502.1 N compared to 374.6 N, P <
      0.001). The rate of decrease in Fr was significantly slower for LE than HG for
      the first 25 s of the exercise (phase 1 of AIC). The Fr developed by the subjects
      at the end of AIC was 40% MVC for both LE and HG. The increase in fc was greater
      for LE (63 beats.min-1) than for HG (52 beats.min-1), P < 0.01. The SVI decreased
      significantly from the resting level by 17.0 ml.m-2 and by 18.2 ml.m-2 for LE and
      HG, respectively. The QcI increased insignificantly for HG by 0.09 l.min-1.m-2
      and significantly for LE by 0.56 l.min-1.m-2 (P < 0.001). It was concluded that
      although both AIC caused a significant decrease in SVI, greater increases in fc
      and Qc were observed for LE than for HG. The greater fc and Qc reported during LE
      was probably related to the greater relative force exerted by LE during phase 1
      of AIC. It seems, therefore that central command might have dominated for phase 1
      of AIC but that the muscle reflex also contributed significantly to the control
      of the cardiac response to the high intensity AIC.

PMID- 8549583
TI  - Intramuscular laser-Doppler flowmetry in the supraspinatus muscle during
      isometric contractions.
AB  - To study the regulation of microvascular blood flow in a compartment muscle,
      laser-Doppler measurements of muscle microcirculation were recorded in the
      supraspinatus muscle in eight volunteers during and following submaximal
      isometric muscle contractions. The subjects performed isometric shoulder
      abductions at five contraction levels from 5% to 50% maximal voluntary
      contraction for 1 min each and a sustained 30 degrees shoulder abduction for 20
      min. The subjects' perceived exertion increased from "no perceived exertion" to
      "near maximal exertion" during the 20-min period with 30 degrees shoulder
      abduction. Microcirculation increased during all 1-min contractions. Following
      the contractions at 20%, 30% and 50% MVC post-exercise reactive hyperaemia was
      seen for a period of at least 1 min. The reactive hyperaemia increased in
      magnitude in response to increasing contraction level. The results showed the
      same time-history of the blood flow at microvascular level as previously seen in
      larger peripheral vessels in response to muscle contractions. During the 20-min
      contraction microcirculation increased in line with the findings during the brief
      contractions. However, in contrast to the brief contractions no postexercise
      reactive hyperaemia occurred following the prolonged contraction. Lack of
      postexercise reactive hyperaemia following the prolonged shoulder abduction would
      suggest insufficient regulation of the vascular resistance. Alternatively, lack
      of hyperaemia could be taken as an indication of sufficient microcirculation
      during the preceding contraction. From previous studies on intramuscular pressure
      and metabolism the latter alternative would seem unlikely.

PMID- 8549584
TI  - Critical power test for ramp exercise.

PMID- 8549585
TI  - Growth factors in skin wound healing.
AB  - The healing of skin involves a wide range of cellular, molecular, physiological
      and biochemical events. During the healing process, cells migrate to wound sites
      where they proliferate and synthesize extracellular matrix components in order to
      reconstitute a tissue closely similar to the original one. This activity is
      regulated by mediators secreted from the wound border cells such as PDGF, EGF,
      TGF beta and many other cytokines. Their effects on cells has been demonstrated
      in vivo and in vitro. The aim of this article is to summarize the sequential
      events that occur during wound healing notably cell migration, proliferation and
      phenotypic differentiation and to describe the cellular interactions involving
      growth factors at the molecular level.

PMID- 8549586
TI  - Behavior of interchromatin granules during the cell cycle.
AB  - We investigated at the ultrastructural level, by different cytochemical and
      immunocytological approaches, the behavior of interchromatin granules (IGs)
      during interphase and mitosis in two cell lines (HEp-2 and Ehrlich tumor cells).
      Identical results were found in all two cell types. In interphase cells, IGs
      group into irregular clusters of varying size. They are frequently associated
      with coiled bodies and homogeneous fibrillar bodies. Analysis of serial sections
      reveals that IG clusters occupy distinct regions within the nucleoplasm. During
      prophase, the aggregation of granules in these clusters gives rise to compact,
      spherical, granular structures. These disperse in the mitotic cytoplasm at the
      breakdown of the nuclear envelope. At early telophase, some of them come into
      close contact with the periphery of reforming nuclei. IG clusters reappear in the
      daughter nuclei only after the chromosomes have decondensed during late
      telophase. Concomitantly, the cytoplasmic granular structures disappear. During
      the cell cycle, IG are silver-stainable and EDTA-positive. They are also
      constantly labeled by the polyadenylate nucleotidyl transferase-immunogold
      technique for detecting RNA. These results support the view that IGs persist
      throughout the whole cell cycle.

PMID- 8549587
TI  - The intranuclear amount of phospholipase C beta 1 decreases following cell
      differentiation in Friend cells, whereas gamma 1 isoform is not affected.
AB  - The existence of a signal transduction system in the nucleus, based on
      polyphosphoinositide breakdown mediated by specific phosphoinositidases (PLC),
      has been widely documented. In different cell systems, nuclear PLCs can be
      modulated, in response to agonists, either by enhancing or by down-regulating
      their activity, thus leading to DNA replication or to cell differentiation.
      Friend cells, induced to erythroid differentiation by dimethyl sulfoxide (DMSO),
      show a down-regulation of PLC beta 1 isoform, as indicated by the reduction of
      the transcription of its mRNA and of the in vitro synthesis of its translation
      product. The intracellular localization and the amount of different PLC isoforms
      have been evaluated by electron microscope immunocytochemistry. In untreated
      Friend cells, PLC beta 1 and gamma 1 isoforms are both present within the
      nucleus, whereas mainly the gamma 1 isoform is detected in the cytoplasm. The
      small amount of cytoplasmic PLC beta 1 is probably representative only of the
      newly synthesized enzyme. Quantitative immunolabeling analyses demonstrate that
      erythroid differentiation is associated with a significant decrease of the PLC
      beta 1 amount in the nucleus and with an almost complete disappearance of that
      isoform in the cytoplasm, whereas the PLC gamma 1 isoform is unaffected. The two
      PLC isoforms, moreover, appear to be differently associated with the nuclear
      components, PLC beta 1 being steadily bound to the inner nuclear matrix, whereas
      PLC gamma 1 is almost completely soluble.

PMID- 8549588
TI  - Alterations in cytoskeletal and nuclear matrix-associated proteins during
      apoptosis.
AB  - Evidence exists that apoptosis or programmed cell death plays an important role
      in tumor growth. Morphologically apoptosis is characterized by membrane blebbing
      and nuclear fragmentation in individual cells. In this study, we investigated
      changes in the nuclear organization in spontaneously occurring apoptotic cells in
      several cancer cell lines using several antibodies to nuclear matrix
      constituents. It appeared that nuclear matrix components remained detectable in
      cells undergoing spontaneous apoptosis. The same results were found when
      apoptosis was induced by cycloheximide in the non-small cell lung cancer cell
      line MR65. Using this induction method, the percentage of apoptotic cells in MR65
      cells increased, allowing a more detailed and extensive examination of nuclear
      matrix alterations together with cytoskeletal changes. To study the expression of
      cytokeratins, type A- and B lamins, a nuclear matrix-associated 13 kDa U1RNP
      particle and the Ki67-antigen, immunocytochemistry in combination with confocal
      scanning laser microscopy was used. Apoptotic cells were identified based on
      nuclear morphology and the in situ nick translation assay. Whereas
      immunoreactivity against lamins and Ki67-Ag was rapidly lost during apoptosis,
      expression of the 13 kDa protein and, in early apoptotic stages, also cytokeratin
      expression, was observed to remain present. Dead cells lacked reactivity with all
      the antibodies tested. The persistence of nuclear matrix components is therefore
      a useful marker for the detection of apoptosis.

PMID- 8549589
TI  - A decrease in intracellular glutathione concentration precedes the onset of
      apoptosis in murine thymocytes.
AB  - Free radical damage has been implicated in the induction of apoptosis in some
      cells. We investigated whether the status of a cell's oxidant defence system is
      involved in the signalling pathways triggering apoptosis. We used three unrelated
      agents, dexamethasone, thapsigargin and gliotoxin to induce apoptosis in
      thymocytes from 10-day-old BALB/c mice. With all stimuli there was a correlation
      between the percentage of cells undergoing apoptosis (as measured with propidium
      iodide DNA staining) and the percentage of cells with lowered [GSH]i. Treatment
      with either 1 mM reduced glutathione or 10 nM thapsigargin inhibited
      dexamethasone-induced apoptosis in thymocytes at 6 h, as well as the rise in the
      percentage of cells with lowered [GSH]i that normally accompanied the onset of
      apoptosis. Furthermore, following treatment of thymocytes with oxidized
      glutathione, a normal product of the action of the cell's oxidant defence system,
      high levels of apoptosis were observed. This suggested that the onset of
      apoptosis was not simply the result of a loss of GSH from the cytosol. From our
      evidence we suggest that a decrease in [GSH]i, or an increase in [GSSG]i or
      perhaps a change in the ratio of [GSH]i to [GSSG]i constitutes a trigger for
      apoptosis.

PMID- 8549590
TI  - Mutations in the v-mos gene abolish its ability to induce differentiation but not
      transformation.
AB  - The v-mos oncogene product has the ability to induce differentiation in human
      monocytic leukemia U937 cells, thereby arresting cell proliferation, and also
      exhibits transforming activity in mouse NIH3T3 cells. Mutation in the v-mos gene
      consisting of one or two amino acid substitutions in the putative ATP-binding
      domain impaired its differentiation-inducing activity although mutant proteins
      showed rather higher levels of autophosphorylation in vitro. Macrophage-specific
      characteristics such as their morphology, expression of C3b receptor and Fc
      receptor, and production of interleukin-1 beta and tumor necrosis factor alpha,
      were equally diminished in cells transfected with mutant mos genes when compared
      to those with intact v-mos. The ability of the gene to arrest the proliferation
      of U937 cells was likewise diminished, while the transforming efficiency of the
      intact and mutant mos genes were essentially the same. These results suggest that
      the mos product functions differently in cell differentiation and transformation.

PMID- 8549591
TI  - Rearrangement of intercellular junctions and cytoskeletal proteins during rabbit
      myocardium development.
AB  - A direct and close association between desmosomes and intermediate-sized
      filaments of the keratin type exists in embryonic and in adult epithelial
      tissues. Cardiomyocytes are interconnected by spot-desmosomes, which are found in
      the intercalated disks and can be immunocytochemically detected by antibodies to
      desmoplakins. In this study, at the light microscopical level, we describe an
      interaction of keratin filaments with desmoplakins during rabbit
      myocardiogenesis. In the early stages (0-1 somites), desmoplakins are more
      abundant in the heart anlagen than in the adjacent intra- and extraembryonic
      mesoderm. During development of the myocardium, desmoplakin expression gradually
      rearranges from an apicolateral into an intercalated disk localization in later
      states. Keratin expression in the developing myocardium of the rabbit heart
      decreases with the age of the embryo. Keratin filaments are gradually lost via
      dot-like aggregates which colocalize with desmoplakin-positive clusters. Our
      results suggest a role for keratins in the developmental rearrangement of
      desmoplakins into the intercalated disks. A direct relation of desmin and titin
      reorganization to desmoplakin rearrangement, which was examined because of the
      dominant role of these proteins in cardiogenesis, was not found.

PMID- 8549592
TI  - Heterogeneous responsiveness of the in situ rat vascular endothelial cells to
      mechanical stretching in vitro.
AB  - En face endothelial cell (EC) sheets from various vessels of the rat vascular
      tree were stained with rhodamine-phalloidin to examine the response of the ECs to
      mechanical stretching, especially from the viewpoint of actin stress fiber (SF)
      dynamics. Arterial ECs were classified into three types according to the
      distribution pattern of their SFs before and after stimulation. In both ECs with
      few SFs from arteries near the heart and those having many SFs from arteries
      distributed in the uterus, ovary or kidney, new SF formation was not induced by
      stretching. ECs with various amounts of SFs from the abdominal aorta to the
      femoral artery developed many SFs in response to stretching. On the other hand,
      the response of venous ECs with initially few SFs was generally low, although
      active SF formation was observed in ECs from the uterine vein, portal vein and
      anterior facial vein, which are normally subjected to higher levels of mechanical
      stress in situ. The amplitude of stretching necessary for SF formation in ECs was
      about 40% in both vascular systems, although the time necessary for SF expression
      was 10 min and 30 to 40 min in arterial and venous ECs, respectively. A rapid
      increase in the number of ECs with SFs for a given amplituding of stretching
      suggests the presence of a threshold-like value in this reaction system. It was
      clarified that notable heterogeneity of ECs in their response to mechanical
      stress exists among the arterial and venous trees.

PMID- 8549593
TI  - Mobilization of intrasporozoite Ca2+ is essential for Theileria parva sporozoite
      invasion of bovine lymphocytes.
AB  - The entry of Theileria parva sporozoites into bovine lymphocytes occurs rapidly
      and involves a defined series of events. In the present study the role of calcium
      in sporozoite entry was examined. Depletion of Ca2+ from the external medium had
      little effect on sporozoite entry suggesting that the initial sporozoite-host
      cell interaction is a Ca(2+)-independent process. Sporozoite entry could,
      however, be inhibited by a range of Ca2+ channel blockers (verapamil,
      nicardipine, diltiazem) and calmodulin antagonists (TPF, chloropromazine, W7 and
      calmidazolium). Evidence is also presented that demonstrates that sporozoite
      entry is dependent on changes in sporozoite cytosolic Ca2+ caused by the release
      of Ca2+ from intrasporozoite stores. First, reagents that produced an influx of
      Ca2+ into the parasite (A23187) blocked entry. Second, depletion of
      intrasporozoite Ca2+ levels (10 microM A23187 + 1.0 mM EGTA) or an increase in
      the cytoplasmic buffering capacity of the sporozoite cytoplasm (by preloading
      sporozoites with MAPT/AM) inhibited invasion. Third, sporozoite entry was
      inhibited by TMB-8 which blocks the release of Ca2+ from intracellular stores.
      Lastly, treatment of sporozoites with the Ca(2+)-mobilizing agents thapsigargin,
      cyclopiazonic acid but not InsP3 prevented sporozoite entry. In these cases the
      premature release of intrasporozoite Ca2+ inhibited sporozoite binding to the
      host cell surface; sporozoites that bound became internalized at rates comparable
      to the controls. In contrast, treatment of lymphocytes with these reagents had no
      significant effect on sporozoite entry. Collectively these results demonstrate
      that the mobilization of Ca2+ from intrasporozoite stores following sporozoite
      binding to the host cell surface is essential for successful parasite invasion.

PMID- 8549594
TI  - Insulin stimulates the expression of basic fibroblast growth factor in rat brown
      adipocyte primary culture.
AB  - The effect of insulin on the hyperplasia of brown adipose tissue (BAT) was
      investigated using the primary culture of rat brown adipocyte precursor cells
      (RBAC). Results showed insulin to significantly increase the number of RBAC, but
      not bovine capillary endothelial cells, in the presence of fetal bovine serum.
      Insulin also increased the expression of basic fibroblast growth factor (bFGF)
      mRNA and the related protein in the primary culture of RBAC. In addition, insulin
      enhanced the capillary growth in an in vitro angiogenesis model in which
      microvascular fragments and RBAC isolated from rat BAT were grown in coculture.
      The level of bFGF-related protein in the coculture was higher in the presence of
      insulin than in the absence of insulin. These findings suggest that insulin may
      play an important role in the proliferation as well as in the differentiation of
      brown adipocytes, with resulting hyperplasia of BAT (including the formation of
      new capillaries) through increased production of bFGF in brown adipocytes.

PMID- 8549595
TI  - The protein phosphatase inhibitor calyculin-A affects catecholamine secretion and
      granular distribution in cultured adrenomedullary chromaffin cells.
AB  - Calyculin-A, a potent inhibitor of types 1 and 2A protein phosphatases, increases
      basal catecholamine secretion in cultured chromaffin cells with a maximum effect
      observed at 100 nM. This effect was increased by forskolin and the calmodulin
      antagonist W7, but was modified neither by phorbol esters nor the protein kinase
      inhibitor, H7. The effect of the toxin, calyculin-A, on basal secretion was
      completely prevented by the protein kinase inhibitor K252a. In digitonin
      permeabilized cells calyculin-A induced an increase in basal release, but, in
      contrast, it partially reduced calcium-induced secretion. Analysis of total
      proteins revealed that calyculin-A treatment of the cells increased the level of
      phosphorylation of different protein bands. Examination of the Triton X-100
      insoluble fraction revealed a clear increase in the phosphorylation level of
      various proteins, including vimentin. Calyculin-A provoked a rapid morphological
      change in chromaffin cells in the same range of concentration (50-300 nM). Cells
      became rounder and were partially detached from the substratum forming clusters,
      this effect was also blocked by K252a. Transmission electron microscopy of
      calyculin-A-treated cells showed an increase in the proportion of chromaffin
      granules located closer to the membrane. These results suggest that calyculin-A
      induces changes both in the catecholamine secretory response and in the
      cytoskeletal elements of chromaffin cells by protein phosphorylation.

PMID- 8549596
TI  - Affinity-purified antibodies against alpha-galactosyl residues from human serum:
      comparison of their binding in bovine testicular tissue with that of the
      Griffonia simplicifolia lectin (GSI-B4) and impact of labeling on epitope
      localization.
AB  - alpha-Galactosyl residues in the carbohydrate part of cellular glycoconjugates
      can serve as cell type-associated markers and are implicated in intercellular
      adhesion and biosignaling. This biological significance explains the interest to
      characterize probes with respective specificity as the Griffonia simplicifolia I
      isolectin B4. Due to the documented occurrence of an alpha-galactoside-binding
      immunoglobulin G fraction in human serum we compared the extent of binding and
      its pattern for the lectin and the antibody using surface-immobilized extract
      proteins and fixed sections of bovine testicular tissue with known lectin
      reactivity. The antibody fractions were obtained either solely from affinity
      chromatography isolation on immobilized melibiose or after an additional step to
      deplete this fraction of galactoside-binding activities without pronounced
      specificity to the alpha-anomeric linkage. They yielded a rather
      indistinguishable reactivity in comparison to that of the lectin, when an
      indirect approach was used. Labeling of the antibodies with a hydrazide
      derivative of biotin did not affect the pattern of binding. However, significant
      differences were noted, when conjugation of label was targeted to amino groups
      via N-hydroxy-succinimide esters of biotin and digoxigenin despite performance of
      the modification under activity-preserving conditions. Notably, the apparent
      strong staining of Leydig cells and nuclei of primary spermatocytes,
      respectively, was not inhibitable by sugar. These differences were corroborated
      by a nonidentical response of the various probes in solid-phase assays with
      extract proteins. Thus, care should be exercised in the interpretation of
      histochemical data, obtained with this type of modified antibody. When these
      precautions are fulfilled, this immunoglobulin fraction from human serum has the
      potential as an alpha-galactosyl-specific histochemical tool.

PMID- 8549597
TI  - Change in MIB-1 staining between primary and recurrent epithelial ovarian cancer.
AB  - PURPOSE: In recent articles, MIB-1 staining has been shown to relate to length of
      survival of patients with epithelial ovarian malignancies. We report a case
      showing the difference in MIB-1 between the primary and recurrent tumor. CASE
      REPORT: A 63 year old female had a total abdominal hysterectomy, bilateral
      salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy, partial
      omentectomy, and a staging procedure which achieved optimal debulking of a clear
      cell adenocarcinoma of the ovary. Final pathology revealed Stage IIIc disease
      because of one positive left iliac node. All other specimens except for the
      ovaries were negative for malignancy. The proliferation index of the tumor based
      on MIB-1 monoclonal antibody staining was 4.10%. The patient then was treated
      with 6 courses of carboplatin and cyclophosphamide. After a microscopically
      positive second look laparotomy, the patient received 4800 cGy of external beam
      radiation to the pelvic and paraaortic lymph node bearing areas. Fifteen months
      after the original diagnosis, a suspicious vaginal mass was biopsied and found to
      be recurrent clear cell adenocarcinoma consistent with an ovarian primary. MIB-1
      monoclonal antibody staining of the recurrent cancer gave a proliferation index
      of 38.73%. The patients is still alive with a CA-125 which has plateaued between
      60 U/ml and 70 U/ml, fourteen months after recurrence. CONCLUSION: The
      proliferation index by MIB-1 staining may be affected by treatment for ovarian
      epithelial malignancies.

PMID- 8549598
TI  - Synchronous endometrial and ovarian cancer in young woman taking oral
      contraception.
AB  - Oral contraceptives have been reported to confer protective effect against
      tendometrial and ovarian carcinoma. An uncommon presentation of concomitant
      endometrial and ovarian cancer in a young patient using oral contraception is
      reported.

PMID- 8549599
TI  - A meta-analysis of residual disease and survival in stage III and IV carcinoma of
      the ovary.
AB  - A meta-analysis of retrospective studies was performed to determine the value of
      cytoreductive surgery separately for Stage III and IV ovarian cancer. DESIGN: A
      literature search and personal communications were used to identify studies
      reporting patient numbers and survival data at 2 years and/or 5 years in patients
      with no residual, < = 2 cm and > 2 cm residual disease after surgery for Stage
      III and IV ovarian cancer. An odds ratio (OR) with 95% confidence intervals was
      performed on the data using the Cochran-Mantel-Haeszel procedure. RESULTS: The
      results show a survival benefit for patients with nil and < = 2 cm residual
      disease after surgery for both stage III and IV disease when compared to patient
      left with tumor masses > 2 cm. For Stage III patients the OR was 3.98 (3.31 to
      4.79) at 2 years and 5.51 (4.40 to 6.90) at 5 years, indicating with 95%
      confidence that those with < = 2 cm residual tumor survived longer. When
      comparing nil and < = 2 cm residual disease survival is better for the group with
      nil residual with OR 3.37 (2.17 to 5.22) at 2 year and OR 4.35 (2.87 to 6.61) at
      5 years. Optimal cytoreduction was also beneficial in Stage IV with OR 4.94 (2.55
      to 9.57). Although it appears that maximum surgical effort is justified for stage
      III as well as Stage IV ovarian cancer, it must be remembered that no
      prospective, randomized trials have been performed. CONCLUSION: Optimal
      cytoreductive surgery appears to benefit the patient with ovarian cancer, but no
      data from prospective, randomized trials are available and tumor biology is not
      assessed. Very few studies report survival data based on the amount of residual
      disease in the separate FIGO stages. There is a need for a single, large database
      reporting all known variables for each patient.

PMID- 8549600
TI  - Surgical vs. clinical staging of endometrial carcinoma. The impact on treatment
      modification, morbidity and survival.
AB  - OBJECTIVE: To assess the impact of surgical staging on treatment modification and
      outcome in endometrial carcinoma (EC) patients. METHODS: Two groups of
      histologically confirmed clinical Stage I and II EC patients, diagnosed during
      two time periods (1976-1984 and 1985-1991), were retrospectively compared. Sixty
      five patients diagnosed during the first period were staged only clinically and
      treated according to a protocol based on this staging system. Fifty-six patients
      diagnosed during the second period were staged surgically and treatment was
      modified according to surgical pathological findings. RESULTS: The findings based
      on the surgical staging spared radiotherapy in some patients and prompted
      additional treatment in others. The morbidity and survival were similar in the
      two groups. CONCLUSIONS: Surgical pathological findings in EC patients may modify
      management and contribute to prognostic significance. No effect on postoperative
      morbidity or on actuarial survival was demonstrated.

PMID- 8549602
TI  - Expression of p53 and coexistence of HPV in premalignant lesions and in cervical
      cancer.
AB  - Fifty-four paraffin embedded tissue sections from patients with dysplasia (21
      cases) and with cervical cancer (33 cases) were analysed. HPV was detected and
      identified in two stages. Firstly, using mixed starters, chosen genomic DNA
      sequences were amplified; secondly the material thus obtained was analyzed by
      hybridization method using oligonucleotyde 31-P labelled probe. HPVs of type 6,
      11, 16, 18, 33 were identified. The p-53 expression was assayed by
      immunohistochemical method. HPV infection was often associated with dysplasia and
      cervical cancer. In cervical cancer mainly HPV 16 and 18 with high oncogenic
      potential were found. The p-53 was present rarely, and in minute quantities. No
      correlation was observed between presence of p-53 and HPVs DNA.

PMID- 8549601
TI  - The value of TPS in breast cancer.
AB  - The serum concentration of the cell proliferation marker TPS (Tissue Polypeptide
      Specific Antigen) was compared with 7 different common tumor markers (CEA, CA 12
      5, CA 19-9, CA 15-3, ferritin, AFP and beta 2-Microglobulin) in order to assess
      its practical value in the management of breast cancer. The new monoclonal TPS
      assay utilizing the specific epitope M3 is used to monitor cell multiplication in
      cancer patients. The values are not related to tumor burden but rather reflect
      the tumor proliferation rate. In our study no association was found between the
      TPS values and the age of the patients and histologic tumor types. Significant
      correlation was observed between the TPS values and the menopausal status of the
      patient. The regression analyses between TPS and the other markers did not reveal
      a correlation. Association between the TPS values and the CA 15-3 was not found.
      However, strong correlation between CA 15-3 and four other markers was observed.
      Therefore, it was concluded that TPS can provide additional information when used
      in combination with CA 15-3.

PMID- 8549603
TI  - Diagnostic methods of early detection of endometrial hyperplasia and cancer.
AB  - Endometrial carcinoma is the most frequent genital neoplasia in women. Our own
      experience is based on a group of 3310 patients who were studied between 1985 and
      April 1994. In 2148 cases, equivalent to 56.4%, hysteroscopy was performed
      because of the presence of abnormal uterine bleeding (AUB). We found 672
      endometrial hyperplasia (601 low risk-71 high risk) and 93 endometrial carcinoma.
      According to our experience we can assert that: hysteroscopy allows the
      measurement of the extension of the intracavitary neoplastic pathology and the
      definition of its topographic map; it is the only method that allows a target
      biopsy; it facilitates the evaluation of the extension of the neoplasia in the
      cervical canal, with the help of a deep biopsy into the cervical tissue (as
      proposed by La Sala) increasing its diagnostic accuracy.

PMID- 8549604
TI  - Cutaneous metastases from squamous cell carcinoma of the vulva. A case report and
      review of the literature.
AB  - Cancer of the vulva, the fourth most common malignancy of the female genital
      tract, accounts for approximately 4% of all gynecologic malignancies. Only one
      prior case of a cutaneous metastasis from a vulvar cancer has been previously
      reported and involved a FIGO Stage III (T2N1M0) lesion. We report a patient with
      Stage II (T2N0M0) vulvar carcinoma who developed cutaneous metastases. This case
      demonstrates the ability of vulvar carcinoma to disseminate hematogenously,
      despite complete surgical resection with negative skin margins, and negative
      lymph nodes. In addition, this case emphasizes the importance of careful and
      close follow-up of all patients with vulvar carcinoma.

PMID- 8549605
TI  - Solitary metastasis in the tarsus preceding the diagnosis of primary endometrial
      cancer. A case report.
AB  - A solitary metastasis in the left tarsus led to the diagnosis of primary
      endometrial cancer in a 61 year-old patient with no history of postmenopausal
      bleeding. Lower leg amputation, total abdominal hysterectomy, bilateral salpingo
      oophorectomy, and pelvic and paraaortic lymphadenectomy were performed.
      Histopathology showed a well-differentiated endometrioid adenocarcinoma of the
      uterus with a low mitotic rate, but infiltration of the outer third of the
      myometrium and lymph vessel invasion (FIGO Stage IVb). Immunostaining was
      positive for progesterone receptors, but negative for estrogen receptors and p53.
      The lymph nodes were free of metastases. Ascites was positive for malignant
      cells. Postoperatively the patient received carboplatin, cyclophosphamide and
      medroxyprogesterone acetate and is alive with no evidence of disease 10 months
      after diagnosis.

PMID- 8549606
TI  - Primary lymphoma of the ovary. A case report and critical review of the
      literature.
AB  - Primary lymphoma of the ovary is an extremely rare cause of ovarian mass. Few
      cases have been recorded in English literature, and controversy still exists as
      to the existence of such an entity. We present a case whose diagnosis can be
      supported by rigorous diagnostic criteria--a long follow-up after surgery with
      only one course of adjunctive polychemotherapy. This case, together with a review
      of the literature, will enrich our knowledge on the issue and on the treatment of
      these patients.

PMID- 8549607
TI  - Thyroid carcinoma originating in a teratoma of the ovary.
AB  - The malignant degeneration of a cystic teratoma of the ovary is a rare
      complication which different authors place at between 0.8 to 4%. Adenocarcinomas
      represent a relatively rare complication, 8% of secondary cancers, those of
      thyroid origin being reported in only 5 cases. The aim of this paper is to
      present the sixth such case of thyroid carcinoma developed in a mature teratoma
      in the ovary.

PMID- 8549608
TI  - The prognostic significance of cervico-vaginal cytology in endometrial cancer.
AB  - In patients with endometrial cancer, preoperative identification of certain poor
      prognostic factors is helpful in planning therapy. To determine the place of
      cervico-vaginal cytology in this respect, we have studied the relationship
      between cervico-vaginal cytology and the well-known prognostic factors of
      endometrial cancer such as grade, myometrial invasion, peritoneal cytology, stage
      and histological subtype. A hundred and sixty two patients, all of whom underwent
      surgical therapy in our clinic, were included in this study in order to correlate
      the cytological results with the pathological findings. Cervico-vaginal cytology
      was negative in 88 patients (54%), suspicious in 26 patients (16%) and malignant
      in 48 patients (30%). Twenty four per cent of cases with adenocarcinoma and
      adenoachantoma, and fifty two per cent of patients with adenosquamous carcinoma,
      papillary adenocarcinoma and clear cell carcinoma had positive cervicovaginal
      cytology (p < 0.001). Seventy four per cent of patients with negative cervico
      vaginal cytology had grade I tumor, while 5% of patients with negative cytology
      had grade III tumor. On the other hand, only 9% of patients with positive cervico
      vaginal cytology had grade I tumor, while 55% had grade III tumor (p < 0.001). 8%
      of patients with inner 1/2 myometrial invasion had positive cytology, whereas 51%
      of patients with 1/2 outer myometrial invasion had malignant cells in their smear
      (p < 0.001). As for the staging of the endometrial cancer according to FIGO, 19%
      of patients with Stage I disease had positive cervico-vaginal cytology while 60%
      of patients in Stage II and 66% of patients in Stage III-IV had positive cytology
      (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549610
TI  - Subspecialities in gynaecology and obstetrics.

PMID- 8549609
TI  - Cervical intraepithelial neoplasia and human papillomavirus related lesions of
      the genital tract in HIV positive and negative women.
AB  - Two hundred and twenty one women at high risk for HIV (intravenous drug users
      and/or those with infected partners) were investigated, through a self-filled
      questionnaire and gynaecological examination, to define the relationship between
      genital Human Papilloma Virus (HPV) infections, preneoplastic cervical
      intraepithelial lesions (CIN) and behavioural risk factors. In the 121 HIV
      positive women, 58 (47%) had HPV lesions at colposcopic and/or cytologic
      examination and, out of these 58, 23 (40%) had CIN 1, CIN 2 or CIN 3. Six out of
      the 16 cases with CIN 1 and CIN 2 (37%) followed-up showed a rapid progression of
      the lesion to CIN 3; in 3 women the interval was 6 months, in the other 3 about
      12 months. Only 5 (7%) of the remaining 66 women without HPV lesions had a CIN
      lesion, with an obviously significant difference on comparison with HPV positive
      subjects. Sixty two women out of the 121 (52%) had a previous diagnosis of
      condylomata. In the 100 HIV negative women, 23 (23%) had HPV lesions and, among
      these 23, 6 (26%) had CIN 1, CIN 2 or CIN 3; 1 of them had rapid progression from
      CIN 1 to CIN 3 within a year. Only 5 (3%) without HPV infection showed any kind
      of CIN. 33 women out of 100 (33%) had a previous clinical history of condylomata.
      Our findings strongly suggest that HIV infection is associated with HPV lesions
      and that cervical cytological abnormalities develop in this situation. There is a
      need for short interval cytological and colposcopic follow-up for women at high
      risk of HIV infection.

PMID- 8549611
TI  - Ebelactone B, an inhibitor of urinary carboxypeptidase Y-like kininase, prevents
      the development of deoxycorticosterone acetate-salt hypertension in rats.
AB  - Kininogen-deficient Brown Norway Katholiek rats (BN-Ka) excrete little urinary
      kinin, compared with normal rats of the same strain (BN Kitasato rats (BN-Ki)).
      Deoxycorticosterone acetate-salt treatment increased systolic blood pressure in
      both rats, but much faster in BN-Ka than in BN-Ki. Daily subcutaneous
      administration of ebelactone B (15 and 5 mg/kg/day), a rat urinary
      carboxypeptidase Y-like kininase inhibitor, significantly reduced systolic blood
      pressure in BN-Ki, but not in BN-Ka. This treatment significantly increased
      urinary Na+ excretion and reduced Na+ concentration in the erythrocytes in BN-Ki,
      but not in BN-Ka. An angiotensin-converting enzyme inhibitor, lisinopril (5
      mg/kg/day s.c.), did not reduce the systolic blood pressure in either BN-Ki or BN
      Ka. These results suggested that ebelactone B has promise as a preventive agent
      for the development of hypertension acting through the inhibition of urinary
      kinin degradation.

PMID- 8549612
TI  - Possible involvement of protein kinases in physical dependence on opioids:
      studies using protein kinase inhibitors, H-7 and H-8.
AB  - Effects of a cAMP-dependent protein kinase and protein kinase C inhibitor, H-7 (1
      (5-isoquinolinesulfonyl)-2-methylpiperazine) and a cAMP- and cGMP-dependent
      protein kinase inhibitor, H-8 (N-[2-(methylamino)ethyl]-5
      isoquinolinesulfonamide), on the behavioral signs of naloxone (an opioid receptor
      antagonist)-precipitated withdrawal syndrome and effects of H-7 on the change of
      protein kinase C activity in the pons/medulla region induced by morphine (a mu
      opioid receptor agonist) or butorphanol (a mu/delta/kappa mixed opioid receptor
      agonist) were investigated in this study. Rats were intracerebroventricularly
      (i.c.v.) infused with morphine (26 nmol/microliters/h) or butorphanol (26
      nmol/microliters/h) through osmotic minipumps for 3 days. In some groups, either
      saline or drug-treated groups were concomitantly infused with H-7 (1 and 10
      nmol/microliters/h) or H-8 (10 nmol/microliters/h). The expression of physical
      dependence produced by morphine or butorphanol, as evaluated by naloxone (5 mg/kg
      i.p.)-precipitated withdrawal signs, was reduced by concomitant infusion of H-7
      or H-8. In the same condition, morphine and butorphanol chronic treatment
      enhanced (28.1% and 26.3% enhancement over the saline-treated group,
      respectively) cytosolic protein kinase C activity in the pons/medulla, but not in
      the membrane fraction. Furthermore, concomitant infusion of H-7 inhibited the
      enhancement of protein kinase C activity. These results indicate that various
      types of protein kinases may play an important role in the development and/or
      expression of physical dependence on opioids. Among them, the enhancement of
      cytosolic protein kinase C activity in the pons/medulla region seems to be one of
      the major underlying mechanisms in opioid physical dependence.

PMID- 8549613
TI  - MDL 100,458 and MDL 102,288: two potent and selective glycine receptor
      antagonists with different functional profiles.
AB  - Glycine receptor antagonists have been proposed to have multiple therapeutic
      applications, including the treatment of stroke, epilepsy, and anxiety. The
      present study compared the biochemical and behavioral profiles of two strychnine
      insensitive glycine receptor antagonists, MDL 100,458 (3-(benzoylmethylamino)-6
      chloro-1H-indole-2- carboxylic acid) and MDL 102,288 (5,7-dichloro-1,4-dihydro-4
      [[[4- [(methoxycarbonyl)amino]phenyl]sulfonyl]imino]-2-quinolinecarboxylic acid
      monohydrate). Both compounds potently inhibited [3H]glycine binding to rat
      cortical/hippocampal membranes (Ki = 136, 167 nM, respectively) without showing
      significant activity in 18 other receptor binding assays. In an in vitro
      functional assay, both compounds completely antagonized N-methyl-D-aspartate
      (NMDA)-stimulated cGMP accumulation in rat cerebellar slices. However, in
      contrast to their equipotency in the glycine receptor assay, MDL 100,458 was
      approximately 6-fold more potent than MDL 102,288 in the cGMP assay (IC50 values
      = 1.25, 7.8 microM, respectively). Behavioral tests demonstrated that MDL 102,288
      and MDL 100,458 exhibited strikingly different in vivo profiles. MDL 100,458
      antagonized audiogenic seizures in DBA/2J mice (ED50 = 20.8 mg/kg i.p.), whereas
      MDL 102,288 was without effect in the dose range tested (ED50 > 300 mg/kg i.p.).
      Central nervous system penetration did not appear to account for this difference.
      For example, MDL 102,288 was not active following direct intracerebroventricular
      administration (ED50 > 16 micrograms; vs. 0.78 microgram for MDL 100,458). In a
      test of anxiolytic activity, MDL 102,288 reduced separation-induced ultrasonic
      vocalizations in rat pups (ED50 = 6.3 mg/kg i.p.) whereas MDL 100,458 was only
      weakly active (ED50 = 80.8 mg/kg i.p.). Furthermore, the anxiolytic effect of MDL
      102,288 was selective in that it occurred at doses that did not produce motoric
      disruption as measured by an inclined-plane test (ED50 > 160 mg/kg; therapeutic
      index > 25.4). In contrast, the anxiolytic activity of MDL 100,458 was non
      selective in that it occurred at doses that also produced motoric disruption
      (ED50 = 57.7 mg/kg; therapeutic index = 0.7). Thus, two glycine receptor
      antagonists which have similar in vitro binding profiles as selective ligands for
      the strychnine-insensitive glycine receptor, demonstrate different in vitro and
      in vivo functional profiles. The reason for these differences is not clear,
      though one possibility could be that the compounds may act on different NMDA
      receptor subtypes. These data support the possibility that different glycine
      receptor antagonists may have different therapeutic targets.

PMID- 8549614
TI  - Characterization of the positive and negative inotropic effects of acetylcholine
      in the human myocardium.
AB  - In the human isolated myocardium, acetylcholine (10(-9) to 10(-3) M) elicited a
      biphasic inotropic effect (a decrease in the lower and an increase in the higher
      concentration range) in atrial and a positive inotropic effect in ventricular
      trabeculae. However, under conditions of raised contractility achieved by
      exposure to noradrenaline (10(-5) M), only negative inotropic effects were
      observed in both atria and ventricles. Atropine (10(-6) M), but not propranolol
      (10(-6) M), antagonized both positive and negative inotropic effects of
      acetylcholine, thus showing that the responses were mediated by muscarinic
      acetylcholine receptors. The use of subtype selective muscarinic receptor
      antagonists (10(-7) to 10(-5) M), pirenzepine (M1 > M3 > M2), AF-DX 116 (11-([2
      [(diethylamino)-methyl]-1-piperidyl]acetyl)-5,11-dihydro-6H- pyridol[2,3
      b][1,4]benzodiazepine-6-one base; M2 > M1 > M3) and HHSiD (p-fluorohexahydro
      siladifenidol hydrochloride; M3 > or = M1 >> M2) revealed that the negative
      inotropic effect of acetylcholine in atrial as well as the positive inotropic
      effect in ventricular trabeculae were best antagonized by AF-DX 116 and not by
      pirenzepine, suggesting the involvement of the muscarinic M2 receptor subtype,
      possibly linked to different second messenger systems. On the other hand, the
      positive inotropic effect of acetylcholine (10(-6) to 10(-3) M) in the atrial
      tissue, observed only in preparation with depressed contractility, was not
      effectively antagonized by either AF-DX 116 or HHSiD, but was significantly
      reduced by pirenzepine. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549615
TI  - Lamotrigine has no antiparkinsonian activity in rat models of Parkinson's
      disease.
AB  - In rodent models of Parkinson's disease such as reserpinized or 6-hydroxydopamine
      substantia nigra lesioned rats, blockade of glutamate receptors of the NMDA (N
      methyl-D-aspartate) or the AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate) receptor subtypes and concomitant treatment with L-DOPA (L
      3,4-dihydroxyphenylalanine) or direct dopamine agonists restores locomotor
      activity and induces rotations. An alternative approach to interfere with
      glutamatergic transmission would involve the inhibition of glutamate release
      resulting in functional glutamate antagonism. The novel antiepileptic drug
      lamotrigine blocks the veratridine-evoked release of the excitatory transmitters
      L-glutamate and L-aspartate. Due to its presumed antiglutamatergic action it has
      been suggested that lamotrigine may be useful in the treatment of Parkinson's
      disease. In a preliminary open-label study in patients with Parkinson's disease
      some favourable effects were reported. The present study was undertaken to
      systematically investigate the effects of lamotrigine in rat models of
      Parkinson's disease. However, lamotrigine failed to exert antiparkinsonian
      activity in reserpinized rats when administered alone or in combination with the
      dopamine receptor agonist apomorphine. In rats bearing 6-hydroxydopamine lesions
      of the substantia nigra lamotrigine did not induce rotations when given alone and
      did not modify rotations induced by apomorphine or the preferential dopamine D2
      receptor agonist lisuride. On the basis of these negative results it is predicted
      that lamotrigine will not have significant favourable effects on akinesia and
      rigidity in Parkinson's disease patients.

PMID- 8549616
TI  - Apomorphine produced more yawning in Sprague-Dawley rats than in F344 rats: a
      pharmacological study.
AB  - Apomorphine induced yawning in both Sprague-Dawley and F344 rats in the same dose
      range, but F344 rats emitted only about 1/4 as many yawns as did Sprague-Dawley
      rats. At higher doses, rats of both strains exhibited stereotypic behavior with a
      comparable intensity. Pretreatment with either SCH 23390 [R(+)-8-chloro-2,3,4,5
      tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l] or pindolol increased
      apomorphine-induced yawning further in Sprague-Dawley rats, but had little effect
      on the low yawning score produced by apomorphine in F344 rats. The low yawning
      response to apomorphine in F344 rats is, therefore, not due to a high baseline
      dopaminergic or adrenergic activity. Apomorphine-induced yawning in F344 rats was
      increased after an acute injection of physostigmine, or 24 h after an injection
      of reserpine. It is postulated that a low baseline cholinergic activity in F344
      rats may be responsible, in part, for their lower yawning response to
      dopaminergic receptor stimulation.

PMID- 8549617
TI  - Discriminative stimulus properties of flesinoxan: effects of enantiomers, (S)
      UH301 and WAY-100635.
AB  - Rats were trained to discriminate the specific 5-HT1A receptor agonist (+)
      flesinoxan (R(+)-N(-)[2[4-(2,3-dihydro-2-2-hydroxy-methyl-1,4- benzodioxin-5-yl)
      1-piperazinyl]ethyl]-4-fluorobenzoamide) (1.5 mg/kg p.o.) from water in a two
      lever operant procedure. Generalization tests were conducted with the enantiomers
      and racemate of flesinoxan and the 5-HT1A receptor antagonists (S)-UH301 ((S)-5
      fluoro-8-hydroxy-2-(dipropylamino)-tetralin) and WAY-100635 ((N(-)[2(-)[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide
      trihydrochloride). (S)-UH301, WAY-100635 and fentanyl were investigated for their
      antagonistic properties. The (+)-flesinoxan stimulus generalized to (-)
      flesinoxan and the racemate. The ED50 values for generalization corresponded well
      with the affinities of the enantiomers and the racemate for the 5-HT1A receptor.
      The flesinoxan cue could not be mimicked by (S)-UH301 or WAY-100635, but (S)
      UH301 reduced response rates. Antagonism tests showed that both (S)-UH301 and WAY
      100635 dose dependently antagonized the flesinoxan cue, with ID50 values of 0.52
      and 0.03 mg/kg s.c., respectively. Fentanyl had no significant antagonistic
      properties. It is concluded that rats can learn to discriminate orally
      administered (+)-flesinoxan from water. The generalization of flesinoxan to the (
      )-enantiomer and the antagonism of flesinoxan's cue by specific 5-HT1A receptor
      antagonists are further evidence for the involvement of flesinoxan's 5-HT1A
      receptor agonistic properties in its discriminative stimulus effects.

PMID- 8549618
TI  - Preferential block of desensitizing AMPA receptor in hippocampal neurons by gamma
      D-glutamylaminomethylsulfonic acid.
AB  - The (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)/kainate
      receptor-channel complex mediates fast components of excitatory synaptic currents
      in the central nervous system. Distinguishing between these components is a
      difficult pharmacological task. As was recently reported, gamma-D
      glutamylaminomethylsulfonic acid (GAMS) may be a selective kainate receptor
      antagonist. We have tested this possibility in experiments which were carried out
      on acutely isolated rat hippocampal neurons. It appeared that 1 mM GAMS first
      blocked 83 +/- 1% of the fast desensitizing 128 microM AMPA-gated current, but
      only 38 +/- 6% of the non-desensitizing current component and reached, at higher
      GAMS concentrations, a plateau at about 50% of the control steady state current
      level. In contrast to the blocking action of GAMS on AMPA-gated currents, 4-fold
      higher concentrations of GAMS were needed to block currents elicited by 256
      microM kainate application. It is suggested that several subunit compositions of
      the AMPA-gated receptor could coexist on a single hippocampal cell. Furthermore,
      GAMS has a certain preference for subunit assemblies which could mediate fast
      desensitizing and, a portion of, the non-desensitizing current component.

PMID- 8549619
TI  - Site of action of galanin in the cholinergic transmission of guinea pig small
      intestine.
AB  - The mode and site of action of galanin were examined in the guinea pig small
      intestine. Galanin (3 x 10(-9)-10(-7) M) inhibited the twitch contractions of
      longitudinally and circularly oriented muscle strips mediated by the stimulation
      of cholinergic neurons, but not the contractions mediated by direct stimulation
      of smooth muscle cells with carbachol. Galanin (3 x 10(-9)-10(-7) M) inhibited
      both the electrically stimulated and the tetrodotoxin-resistant high K+ (40 mM)
      induced increase of [3H]acetylcholine outflow from the ileal strips preloaded
      with [3H]choline, in a concentration dependent fashion. The inhibitory effect of
      galanin was antagonized by galantide and produced self-desensitization. The
      spontaneous and stimulated outflow of [3H]noradrenaline and [3H]gamma
      aminobutyric acid were not affected by galanin even at 10(-7) M. Thus, galanin
      inhibits the motility of guinea pig ileum by inhibition of acetylcholine release
      from the enteric cholinergic neurons. Galanin may act on the specific receptor
      located on soma-dendritic regions and nerve terminals of cholinergic neurons.

PMID- 8549620
TI  - In vivo pharmacological characterization of UP 269-6, a novel nonpeptide
      angiotensin II receptor antagonist.
AB  - UP 269-6, 5-methyl-7-propyl-8(-)[2'-(1H-tetrazol-5-yl)biphenyl-4- yl)methyl]
      1,2,4-triazolo]1,5-c]pyrimidin-2(3H)-one is a novel nonpeptide angiotensin II
      receptor antagonist. In vivo studies were performed to evaluate UP 269-6 for its
      angiotensin II antagonistic action. In pithed rats, i.v. administration of UP 269
      6 (0.03-1 mg/kg) shifted dose dependently to the right the dose-pressor response
      curve for angiotensin II and decreased the maximum response. The angiotensin II
      antagonistic effect of UP 269-6 was as potent as that of L-158,809 (5,7-dimethyl
      2-ethyl-3(-)[[2'- (1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazo[4,5-b]pyridine)
      and 10 times more potent than that of losartan. UP 269-6 antagonized the
      angiotensin II sympathetic-mediated tachycardiac response. UP 269-6 inhibited
      dose dependently the pressor response to angiotensin II with an ID50 of 4.5
      micrograms/kg, i.v. in conscious normotensive dogs. Oral administration of UP 269
      6 (0.1 to 30 mg/kg) resulted in a dose-dependent and long-lasting inhibition of
      the angiotensin II-induced pressor response in conscious normotensive rats and
      dogs. Compared to losartan, UP 269-6 presented a more rapid onset of action. UP
      269-6 caused similar angiotensin II antagonistic effects in rats and dogs but the
      duration of the effect was greater in dogs than in rats. UP 269-6 did not alter
      the tachycardiac response to isoproterenol and the pressor response to
      vasopressin. UP 269-6 was demonstrated to be devoid of agonistic properties in
      rats and dogs. Furthermore, UP 269-6 did not induce hypotension and did not cause
      alteration in heart rate and ECG waveforms in dogs even at a dose 1000 times
      higher than the angiotensin II antagonistic effective dose. These results
      demonstrate that UP 269-6 is a potent and specific angiotensin II receptor
      antagonist and dose not possess agonistic properties.

PMID- 8549621
TI  - Estrogenic control of monoamine oxidase A activity in human neuroblastoma cells
      expressing physiological concentrations of estrogen receptor.
AB  - Several lines of evidence support the hypothesis of a role played by estrogens in
      the manifestation of affective disorders in women. The analysis of the mechanism
      of action of a number of antidepressant drugs clearly demonstrated the
      involvement of the catecholaminergic system in the etiology of these complex
      behavioral pathologies. The present in vitro study was therefore undertaken to
      investigate the presence of a functional link between estrogen and catecholamine
      metabolism in cells of neural origin. The model system utilized was a human
      neuroblastoma cell line which was obtained by stable transfection of the estrogen
      receptor cDNA (SK-ER3). The present study shows that in SK-ER3 activation of the
      estrogen receptor correlates with a marked decrease in monoamine oxidase A
      activity. This effect is observed following treatment with a physiological
      concentration of 17 beta-estradiol and can be blocked by the specific antagonist
      of the steroid receptor, ICI 182,780. Dibutyryl cyclic AMP acting, like
      estrogens, on the state of differentiation of SK-ER3 cells did not affect
      monoamine oxidase A activity. The present study provides strong evidence of a
      strict relationship between estrogen receptor and monoamine oxidase A activity in
      human cells of neural origin, thus favoring the hypothesis of an antidepressive
      effect of estrogens exerted via inhibition of the monoamine oxidative pathway.

PMID- 8549622
TI  - Electrical and mechanical responses produced by nerve stimulation in detrusor
      smooth muscle of the guinea-pig.
AB  - In smooth muscles of the guinea-pig bladder, intramural nerve stimulation
      generated an excitatory junctional potential (e.j.p.), action potential and
      twitch contraction. Nicardipine inhibited the action potential but not the e.j.p.
      The e.j.p. amplitude was reduced by suramin, or desensitization of the ATP
      receptor with receptor agonists. The amplitude of the twitch contraction was
      reduced by atropine, and the remainder was blocked by nicardipine. In the
      presence of maximally effective concentrations of atropine, the threshold
      concentration of acetylcholine required to produce contraction was about 10(-7)
      M, whereas acetylcholine concentrations greater than 10(-6) M were required to
      cause depolarization. It is concluded that nerve stimulation releases
      acetylcholine and ATP, and the former produces contraction without change in the
      membrane potential, while the latter generates the e.j.p. which triggers an
      action potential and thus elicits contractions.

PMID- 8549623
TI  - Stimulation of spinal delta-opioid receptors in mice selectively enhances the
      attenuation of delta-opioid receptor-mediated antinociception by antisense
      oligodeoxynucleotide.
AB  - Intrathecal (i.t.) pretreatment of male ICR mice with antisense
      oligodeoxynucleotide to delta-opioid receptor mRNA once a day for 1-3 days caused
      a time-dependent attenuation of i.t. administered [D-Ala2]deltorphin II-induced
      antinociception as measured by the tail-flick test. The attenuation of the
      antinociception induced by i.t. administered [D-Ala2]deltorphin II, a delta
      opioid receptor agonist, was enhanced by i.t. pretreatment for 1 day with [D
      Ala2]deltorphin II, but not [D-Ala2,N MePhe4,Gly(ol)5]enkephalin (DAMGO), a mu
      opioid receptor agonist, or U50,488H, a kappa-opioid receptor agonist, given
      together with antisense oligodeoxynucleotide to delta-opioid receptor mRNA. The
      present results indicate that stimulation of spinal delta-opioid receptors by
      i.t. injection of [D-Ala2]deltorphin II selectively causes a loss of delta-opioid
      receptor-mediated antinociception in mice pretreated with antisense
      oligodeoxynucleotide to delta-opioid receptor mRNA.

PMID- 8549624
TI  - 8-OH-DPAT stimulates gastric acid secretion through a vagal-independent, adrenal
      mediated mechanism.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a neuroendocrine component of the
      gastrointestinal tract. 5-HT1A receptors exist both in the brain and have been
      demonstrated autoradiographically in high density in the rat stomach. However,
      the physiologic role of 5-HT1A receptors in modulating gastric function is not
      known. The effect of the selective 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(n
      dipropylamino)tetralin (8-OH-DPAT), on gastric acid secretory function was
      compared to 5-HT in acute, urethane-anesthetized gastric-fistulated rats during
      pentagastrin infusion. 5-HT inhibited, but 8-OH-DPAT stimulated, gastric acid
      secretion in a dose-dependent manner. Bilateral cervical vagotomy or celiac
      ganglionectomy did not reverse the effect of 8-OH-DPAT on acid secretion.
      However, the enhancement of acid by 8-OH-DPAT was attenuated by acute
      adrenalectomy or close intra-arterial administration of spiperone, but not
      idazoxan. Thus, the data suggest that the selective 5-HT1A receptor agonist 8-OH
      DPAT may augment gastric secretory function via an adrenal-dependent mechanism.

PMID- 8549625
TI  - Potentiation of morphine analgesic action in mice by beta-carotene.
AB  - beta-Carotene was found to potentiate morphine analgesia in hot plate experiments
      using mice. Response time was increased by about 100%, and the duration of
      analgesia was markedly prolonged. These features of beta-carotene were a function
      of the intact molecule, although the closely related compound, alpha-carotene,
      also exhibited this property. beta-Carotene alone had no effect on the
      nociceptive response. Other compounds with related structures, metabolic
      products, or anti-oxidants neither augmented nor antagonized morphine action.

PMID- 8549626
TI  - Discriminative stimulus properties of morphine mediated by mu 1-opioid receptors.
AB  - The mu-opioid receptor subtypes involved in the discriminative stimulus
      properties of morphine were investigated in rats that had been trained to
      discriminate between 3.0 mg/kg morphine and saline. The discriminative stimulus
      properties of morphine were significantly attenuated by beta-funaltrexamine (an
      irreversible mu-opioid receptor antagonist: 10 and 20 mg/kg) and naloxonazine (an
      irreversible mu 1-opioid receptor antagonist: 20 mg/kg). These results suggest
      that the discriminative stimulus properties of morphine may be mediated by mu 1
      opioid receptors.

PMID- 8549627
TI  - The imidazoline I1 receptor agonist, moxonidine, inhibits insulin secretion from
      isolated rat islets of Langerhans.
AB  - In order to study the pharmacology of the putative imidazoline receptor involved
      in stimulation of insulin secretion, the potent and selective imidazoline I1
      receptor agonist, moxonidine, was employed. Surprisingly, this agent caused a
      rapid and complete inhibition of glucose-induced insulin secretion in isolated
      rat islets of Langerhans. This response was reversible upon removal of the
      compound but was only partially attenuated under conditions of complete alpha 2
      blockade, suggesting that it did not derive entirely from the weak alpha 2
      adrenoceptor agonist activity of moxonidine. Furthermore, the response could not
      be attributed to activation of imidazoline I1 receptors since it was not
      reproduced by a second potent imidazoline I1 receptor agonist, cimetidine, and
      could not be alleviated by the imidazoline I1 receptor antagonist efaroxan. The
      results confirm that the imidazoline receptor involved in control of insulin
      secretion differs from the I1 subclass and suggest that moxonidine inhibits
      insulin secretion by a mechanism unrelated to imidazoline I1 receptor agonism.

PMID- 8549628
TI  - Functional correlates of repeated administration of cocaine and apomorphine in
      the rat.
AB  - The [14C]2-deoxyglucose method was applied to measure the effects of repeated (8
      consecutive days) administration of apomorphine (0.5 mg/kg/day s.c.) or cocaine
      (15 mg/kg/day i.p.) on cerebral glucose utilization in freely moving rats.
      Altered rates of glucose utilization were measured in extrapyramidal motor areas,
      such as the globus pallidus, entopeduncular nucleus, subthalamic nucleus,
      substantia nigra and lateral habenula of both cocaine- and apomorphine-treated
      rats. Furthermore, cocaine-treated animals displayed increased glucose metabolism
      in the mesolimbic dopaminergic projections, such as nucleus accumbens and
      olfactory tubercle, and in the hippocampus. These results suggest that altered
      functional activity within the dopaminergic mesolimbic system may play a role in
      the process of sensitization to psychomotor stimulant drugs.

PMID- 8549629
TI  - Involvement of bradykinin in endotoxin-induced vascular permeability increase in
      the skin of rats.
AB  - The aim of the present study was to investigate the role of bradykinin as well as
      that of platelet-activating factor in the endotoxin-induced acute vascular
      permeability increase in the dorsal skin of rats by use of kininogen-deficient
      and normal Brown-Norway rats. In the kininogen-deficient rats, the dose-dependent
      dye exudation induced by endotoxin was about one half of that in the normal rats
      at any doses of endotoxin tested (0.1-1.0 mg per site), whereas the dose-response
      curves obtained by bradykinin (1-100 nmol per site), platelet-activating factor
      (0.1-1 nmol per site) or histamine (50-500 nmol per site) were the same in both
      rats. This effect induced by endotoxin in the kininogen-deficient rats was not
      changed by pretreatment with a bradykinin B2 receptor antagonist, HOE140 (D-Arg
      [Hyp3,Thi5,D-Tic7,Oic8]bradykinin, 1 mg kg-1 i.v.), whereas the endotoxin-induced
      response in the normal rats was attenuated by the receptor antagonist. These
      responses in both kininogen-deficient and normal rats were significantly
      inhibited by a selective platelet-activating factor antagonist, TCV309 (3-bromo-5
      [N-phenyl-N-[2-[[2-(1,2,3,4,-tetrahydro-2- isoquinolylcarbonyl-oxy)-ethyl]
      carbamoyl]-ethyl]carbamoyl]-1-prop yl- pyridinium nitrate, 0.1 mg kg-1 i.v.).
      These results suggest that bradykinin could be one of the major mediators in the
      endotoxin-induced vascular permeability increase in rat skin in addition to
      platelet-activating factor.

PMID- 8549630
TI  - Effects of des-Asp-angiotensin I on the electrically stimulated contraction of
      the rabbit pulmonary artery.
AB  - In the presence of 3 x 10(-6) M captopril, 5 x 10(-7) M des-Asp-Angiotensin I was
      found to inhibit the electrically (1 and 2 Hz) induced contraction of the rabbit
      pulmonary artery but had no significant effect on the noradrenaline-stimulated
      contraction. 2.8 x 10(-6) M indomethacin and 10(-6) M losartan but not 10(-6) M
      (S) 1-([4-(dimethylamino)-3-methylphenyl]methyl)-5-(diphenylacetyl)-4, 5,6,7-
      tetrahydro-1H-imidazo(4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate,
      dihydrate (PD123319) attenuated the inhibition. The inhibition of the
      electrically stimulated contraction by 5 x 10(-7) M des-Asp-angiotensin I
      coincided with a significant drop in the accompanying evoked 3H overflow from re
      uptaken [3H]noradrenaline. The results indicate that des-Asp-angiotensin I acts
      presynaptically on a subtype of angiotensin receptor that involves the release of
      prostaglandin(s). In addition, this receptor subtype is susceptible to blockade
      by angiotensin AT1- but not AT2-specific receptor antagonists. It was suggested
      that this receptor subtype is identifiable with the recently described
      angiotensin AT1B receptor subtype found in the brain, pituitary and adrenal
      glomerulosa. These findings demonstrated a direct action of sub-micromolar
      concentrations of des-Asp-angiotensin I on a blood vessel and indicate that the
      nonapeptide is an active angiotensin per se.

PMID- 8549631
TI  - Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.
AB  - Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of
      asthma; however, little is known of its direct effect on smooth muscle
      reactivity. We investigated the effect of TNF alpha on the responsiveness of
      human bronchial tissue to electrical field stimulation in vitro. Incubation of
      non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased
      responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/-
      2% respectively) compared to control (99 +/- 2%) (P < 0.05, n = 6). Responses
      were not increased in sensitized tissue (101 +/- 3% versus 105 +/- 5%, n = 3, P >
      0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%,
      n = 3, P = 0.38). These results show that TNF alpha causes an increase in
      responsiveness of human bronchial tissue and that this occurs prejunctionally on
      the parasympathetic nerve pathway. This is the first report of a cytokine
      increasing human airway tissue responsiveness.

PMID- 8549632
TI  - mu- and delta-opioid receptor antisense oligodeoxynucleotides antagonize morphine
      induced growth hormone secretion in rats.
AB  - Effects of i.c.v. pretreatment with antisense oligodeoxynucleotides (antisense
      oligos) targeted against either mu- or delta-opioid receptors on morphine-induced
      release of growth hormone (GH) and prolactin were studied in male rats. The
      stimulation of GH secretion by i.c.v. morphine was completely inhibited by the
      antisense oligo targeted against the cloned mu-opioid receptor and significantly
      reduced by the antisense oligo targeted against the cloned delta-opioid receptor.
      The antisense oligo targeted against the cloned mu-opioid receptor, but not that
      targeted against the cloned delta-opioid receptor, abolished the stimulatory
      effect of acute morphine on prolactin secretion. It is concluded that both the GH
      and prolactin secretion stimulating effect of morphine is mainly mediated by the
      cloned mu-opioid receptor. Further, the cloned delta-opioid receptor is involved
      in the morphine-induced stimulation of GH secretion.

PMID- 8549633
TI  - Isoenzymes of cyclic nucleotide phosphodiesterase in the human aorta:
      characterization and the effects of E4021.
AB  - In extracts of the human aorta, five isoenzymes of cyclic nucleotide
      phosphodiesterase, namely, phosphodiesterase I, phosphodiesterase II,
      phosphodiesterase III, phosphodiesterase IV and phosphodiesterase V, were
      identified exclusively in the cytosolic fraction, and no phosphodiesterase
      activity was detected in the particulate fraction. Phosphodiesterase V and
      phosphodiesterase I were the major cGMP-hydrolyzing enzymes in the human aorta. A
      novel vasorelaxant, sodium 1-[6-chloro-4-(3,4
      methylenedioxybenzyl)aminoquinazolin-2-yl ]piperidine-4- carboxylate
      sesquihydrate (E4021), relaxed prostaglandin F2 alpha-precontracted strips of
      human pulmonary artery with an ED50 value of 0.5 microM. E4021 potently and
      highly selectively inhibited the activity of phosphodiesterase V from human aorta
      with a Ki value of 2.4 nM. These results suggest that there is a unique
      distribution of phosphodiesterase isoenzymes in the human aorta and that
      inhibitors of phosphodiesterase V might be useful as a new type of vasodilator in
      the treatment of clinical disorders.

PMID- 8549634
TI  - Inhibition of ATP-sensitive K+ channels of mouse skeletal muscle by disopyramide.
AB  - Single ATP-sensitive K+ channels (KATP channels) were studied in inside-out
      membrane patches excised from mouse skeletal muscle. The class Ia antiarrhythmic,
      disopyramide (5-100 microM), applied to the cytoplasmic membrane surface
      inhibited KATP channels at -40 and +40 mV. Channel inhibition by disopyramide
      started slowly and reached an almost stationary level within 1 min. Recovery from
      channel inhibition by disopyramide was incomplete. At pH 7.4, the disopyramide
      concentrations producing 50% channel inhibition were 8.1 microM at -40 mV and 7.1
      microM at +40 mV. The Hill coefficients of the concentration-response curves were
      close to unity at both potentials. Raising the internal pH from 7.4 to 8.0 had no
      significant effect on the actions of disopyramide, but lowering the pH to 6.5
      greatly potentiated the inhibition of KATP channels by the antiarrhythmic. Thus
      the open probabilities of KATP channels at -40 mV and in the presence of
      disopyramide (20 microM) were smaller by a factor of 18 at pH 6.5 than at pH 7.4.
      The results suggest that disopyramide interacts with KATP channels through the
      lipid phase of the membrane and that lowering the intracellular pH increases the
      affinity of KATP channels to disopyramide. Thus disopyramide at therapeutic
      concentrations (6-15 microM) affects muscular KATP channels, in particular at
      reduced intracellular pH values that occur under ischaemic conditions and during
      fatiguing exercise.

PMID- 8549635
TI  - The inhibition of ornithine decarboxylase activity in developing rat tissues by
      central nervous system beta-endorphin is mediated by mu-opioid receptors, but not
      by delta- or epsilon-opioid receptors.
AB  - Our laboratory has previously shown that intracerebroventricular (i.c.v.)
      administration of beta-endorphin suppresses brain and liver ornithine
      decarboxylase activity (ODC; a growth regulatory enzyme) in preweanling rats.
      This investigation examined, in 6-day-old rats, the relative participation of
      brain mu-, delta- and epsilon-opioid receptors in beta-endorphin's ODC effects,
      by comparing tissue ODC responses to beta-endorphin given alone i.c.v. and in the
      presence of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-opioid receptor
      antagonist), N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174,864; delta-opioid
      receptor antagonist) or beta-endorphin-(1-27) (epsilon-opioid receptor
      antagonist). Administration of 0.5 microgram of beta-endorphin alone
      significantly decreased brain and liver ODC activity 4 h after injection, and the
      effect was completely blocked by coinjection of CTOP (0.075 micrograms) but not
      by ICI-174,864 (0.75 or 3.75 micrograms) or beta-endorphin-(1-27) (3.75 or 7.5
      micrograms). The blockade of endogenous opioid:opioid receptor interactions by
      either CTOP (at doses > 0.075 microgram) or ICI-174,864 alone was accompanied by
      increased levels of basal ODC activity. The results obtained demonstrate that
      i.c.v. beta-endorphin downregulates ODC expression in central as well as in
      peripheral tissues by interacting with brain mu-opioid receptors, but not with
      delta- or epsilon-opioid receptors or mu/delta-opioid receptor complexes. Also,
      they indicate that endogenous opioid systems have a tonic inhibitory influence on
      ODC activity which is mediated, at least in part, by mu- and delta-opioid
      receptors.

PMID- 8549636
TI  - Carotid blood flow distribution, haemodynamics and inotropic responses following
      calcitonin gene-related peptide in the pig.
AB  - The sensory neuropeptide, calcitonin gene-related peptide (alpha-CGRP), has been
      implicated in the pathogenesis of migraine headache. The present study aimed to
      evaluate the effects of intracarotid infusions of human alpha-CGRP (10, 30 and
      100 pmol/kg.min; n = 8), as compared to that of saline (4 times; n = 8) on
      haemodynamics and blood flow distribution within the carotid circulation of the
      anaesthetized pig, using the radioactive microsphere method. Furthermore, the
      effects of antimigraine drugs, dihydroergotamine (100 micrograms/kg i.v.; n = 4)
      or sumatriptan (300 micrograms/kg i.v.; n = 4), on these parameters were studied
      in the presence of the infusion of the highest concentration of human alpha-CGRP.
      Additionally, putative positive inotropic responses to human alpha-CGRP (10(-9)
      10(-7) M) were investigated in porcine isolated atrial and ventricular
      trabeculae. Human alpha-CGRP increased carotid artery blood flow and conductance
      dose-dependently, together with an enhancement in vascular pulsations. These
      effects were associated with a fall in systemic blood pressure with concomitant
      increases in heart rate and cardiac output. The increase in carotid blood flow
      was reflected by an increase in total capillary blood flow, predominantly to
      extracerebral tissues including the dura, whereas blood flow through
      arteriovenous anastomoses remained stable. Both dihydroergotamine and sumatriptan
      reduced carotid blood flow and its capillary fraction without affecting systemic
      vascular conductance. In tissues, these drugs reversed blood flow increases due
      to human alpha-CGRP in most extracerebral tissues, but failed to reduce dural
      blood flow. In porcine isolated atrial and ventricular trabeculae, noradrenaline
      (10(-8)-10(-5) M) increased force of contraction in a concentration-dependent
      manner. In contrast, human alpha-CGRP (10(-9)-10(-7) M) failed to increase force
      of contraction in atrial trabeculae (n = 6) and exerted only a moderate
      concentration-dependent positive inotropic effect in ventricular trabeculae
      (approximately 25% of the response to 10(-5) M noradrenaline, n = 10). These data
      indicate that human alpha-CGRP caused arteriolar dilatation together with a fall
      in blood pressure in the pig. The tachycardia may be reflex-mediated, but the
      peptide also exerts a moderate positive inotropic action on ventricular
      trabeculae. The fall in systemic arterial blood pressure and the marked increase
      in capillary blood flow most likely prevented the opening of arteriovenous
      anastomoses. Furthermore, the antimigraine drugs, dihydroergotamine and
      sumatriptan, were able to reverse blood flow changes induced by human alpha-CGRP
      in the porcine carotid circulation.

PMID- 8549638
TI  - The modulation of the increase in rat facial skin blood flow observed after
      trigeminal ganglion stimulation.
AB  - Electrical stimulation of the trigeminal ganglion causes an increase in facial
      skin blood flow in the anaesthetised rat, as measured by laser Doppler flowmetry.
      We investigated the modulation of this neurogenic vasodilator response using
      selective receptor agonists for putative prejunctional inhibitory receptors, as
      well as other pharmacological agents to further characterise this response. [D
      Ala2,Me-Phe4,Gly5-ol]enkephalin (DAGO, a mu-opioid receptor agonist) inhibited
      the vasodilator response in a dose-related (0.058-5.8 mumol/kg i.v.) and naloxone
      sensitive manner. A similar inhibitory response was observed with the local
      anaesthetic lignocaine (2% w/v, s.c. 20 microliters). In contrast, the histamine
      H3-receptor agonist alpha-methylhistamine (15 or 35 mumol/kg, i.v.) and the 5
      HT1D receptor agonists sumatriptan (0.24 or 2.4 mumol/kg, i.v.) and CP 122,288
      (0.0003-3 mumol/kg, i.v.) had no effect on these responses. Similarly, atropine
      (1.5 mumol/kg, i.v.) and indomethacin (28 mumol/kg, i.v.) did not alter the
      vasodilatation observed in this model. In conclusion, only mu-opioid receptor
      activation and local anaesthetic had any inhibitory action on the neurogenic
      vasodilatation observed in this model.

PMID- 8549637
TI  - Nitric oxide induces vascular permeability changes in the guinea pig conjunctiva.
AB  - The role of nitric oxide (NO) as an inflammatory mediator in the mechanism of
      increased microvascular permeability was examined in a guinea pig model of
      allergic conjunctivitis. Topical challenge with antigen, compound 48/80,
      histamine or platelet activating factor (PAF) resulted in a marked increase of
      the conjunctival vascular permeability. Vascular permeability was determined by
      measuring the albumin content in the lavage fluid of the challenged eyes after 30
      min. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) eyedrops caused
      a significant inhibition of the clinical score and the vascular permeability
      after challenge with either antigen, histamine or PAF. Aminoguanidine prophylaxis
      also resulted in a significant inhibition of both the clinical score and vascular
      permeability in response to all the used provocative agents except PAF. Our
      observations indicate that NO is an important factor in the induction of the
      vascular permeability provoked by histamine but seems to play no role in the
      mechanism by which PAF exerts increased vascular permeability in the conjunctiva.

PMID- 8549639
TI  - Characterization of the binding sites for [3H]glibenclamide in rat liver
      membranes.
AB  - The specific binding sites for sulfonylureas in the rat liver membrane fraction
      were demonstrated and characterized. [3H]Glibenclamide binding to the liver
      membrane was specific, time- and temperature-dependent, and reversible. Scatchard
      analysis showed a single class binding site. The dissociation constant (Kd) for
      glibenclamide was 1.1 microM and the binding capacity (Bmax) was 50 pmol/mg
      protein. [3H]Glibenclamide binding could be displaced by other sulfonylureas.
      Half-maximal inhibition of binding (IC50) for glimepiride, gliclazide,
      acetohexamide, tolbutamide and chlorpropamide was 4.2 microM, 74 microM, 0.33 mM,
      0.60 mM, 1.2 mM, respectively. Each value is close to the reported blood
      concentration when a therapeutic dose of each drug is administered orally. The
      order of IC50 values is coincident with the order of potency of the clinical
      hypoglycemic effect of these drugs. We had shown that these concentrations of
      sulfonylureas stimulate 6-phosphofructo-2-kinase in the liver or hepatocytes and
      inhibit phosphoenolpyruvate carboxykinase in the hepatoma cells. The specific
      binding sites demonstrated here may play some roles when sulfonylureas affect
      carbohydrate metabolism in the liver.

PMID- 8549640
TI  - Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo
      microdialysis in the freely moving rat.
AB  - GABAA and GABAB receptor agonists and antagonists were administered locally in
      the striatum of intact and kainic acid lesioned rats. (+/-)-Baclofen, a GABAB
      receptor agonist, significantly decreased the level of extracellular dopamine in
      the striatum of intact rats. (+/-)-Phaclofen, a GABAB receptor antagonist,
      increased the level of extracellular dopamine in the striatum of intact rats and
      to a lesser extent in the striatum after kainic acid lesion. Pregnanolone (5 beta
      pregnan-3 alpha-ol-20-one), a positive allosteric modulator of the GABAA
      receptor, significantly decreased the level of extracellular dopamine in intact
      rats. (-)-Bicuculline, a GABAB receptor antagonist, increased the level of
      extracellular dopamine in the striatum of intact rats, but failed to increase the
      level of extracellular dopamine after kainic acid lesion. The release of
      extracellular dopamine, due to infusion of phaclofen or bicuculline, was totally
      suppressed by tetrodotoxin. These results support a direct influence of GABA on
      the dopaminergic terminals via presynaptic GABAB receptors, while the effects via
      the GABAA receptor seem to be postsynaptic and mediated by striatal interneurons
      or the striatonigral feedback loop.

PMID- 8549641
TI  - Presynaptic actions of glutamate receptor agonists in the CA1 region of rat
      hippocampus in vitro.
AB  - A grease-gap recording technique which allows the monitoring of presynaptic d. c.
      potentials without contamination of potentials from postsynaptic elements was
      used to examine presynaptic actions of glutamate agonists in the CA1 region of
      rat hippocampus. Presynaptic depolarizations through the activation of 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX)- and 2-amino-5-phosphonovaleric acid (APV)
      sensitive receptors could be induced by applied agonists. In addition, the N
      methyl-D-aspartate (NMDA)-induced depolarization was smaller in the presence of
      extracellular Mg2+ suggesting some similarity to postsynaptic NMDA receptors. The
      (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD)-induced
      depolarization was antagonized by L-2-amino-3-phosphonopropionic acid (L-AP3) but
      was also sensitive to APV+CNQX, creating ambiguity as to the type of receptors
      involved. These results suggest that the activation of glutamate autoreceptors
      leads to a presynaptic depolarization.

PMID- 8549642
TI  - Effects of protein kinase A activation on endothelin- and ATP-induced signal
      transduction.
AB  - C6 glioma cells possess endothelin ETA receptor and P2 purinoceptor coupled to
      two signaling pathways, i.e. phosphoinositide turnover and inhibition of adenylyl
      cyclase. In this study, the effects of raising cyclic AMP levels on the inositol
      phospholipid hydrolysis and adenylyl cyclase inhibition caused by endothelin-1
      and ATP in C6 glioma cells were examined. Pretreatment with cAMP generating
      agents (forskolin, isoproterenol and cholera toxin) or dibutyryl cAMP for 10 min
      3 h did not affect the inositol phosphate accumulation caused by endothelin and
      ATP. Long-term (8-24 h) pretreatment with isoproterenol, forskolin, cholera toxin
      or dibutyryl cAMP resulted in a 40-50% inhibition of endothelin- and ATP
      stimulated inositol phosphate accumulation, whereas the EC50 values of endothelin
      and ATP were not affected. Consistent with the effects on endothelin and ATP, NaF
      induced inositol phosphate formation was also inhibited by cAMP generating agents
      to a similar extent. Permeabilized cells from 24 h isoproterenol-or forskolin
      pretreated C6 cells also showed a diminished Ca(2+)-sensitivity of
      phosphoinositide-specific phospholipase C and also attenuated the potentiation
      response caused by GTP gamma S. The inhibitory effects on adenylyl cyclase by
      endothelin, ATP and 2-methylthio-ATP were unaffected by 24 h pretreatment with
      isoproterenol or forskolin. Long-term treatment with dibutyryl cGMP did not
      affect the two signaling pathways caused by ATP and endothelin. It is concluded
      that the phosphoinositide turnover, but not the adenylyl cyclase inhibition
      caused by endothelin and ATP in C6 cells, was inhibited by protein kinase A
      dependent pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549643
TI  - Inhibition of human neutrophil function by tolfenamic acid involves inhibition of
      Ca2+ influx.
AB  - The present work was designed to study the pharmacological control of the
      receptor-mediated activation of human neutrophils by tolfenamic acid (2(-)[(3
      chloro-2-methylphenyl)-amino]benzoic acid). Tolfenamic acid inhibited in a
      concentration-dependent manner the degranulation response and Ca2+ influx in
      neutrophils activated either by the chemotactic peptide fMLP (N-formyl-methionyl
      leucylphenylalanine) or Ca2+ ionophore A23187 (calcimycin). When fMLP was used to
      activate neutrophils, tolfenamic acid (30 microM) reduced Ca2+ influx by 50% and
      degranulation by 20%. A23187-triggered Ca2+ influx and degranulation were
      inhibited by 60% and 40%, respectively, by 30 microM tolfenamic acid. Tolfenamic
      acid did not inhibit the release of Ca2+ from intracellular stores induced either
      by fMLP or A23187. To confirm the inhibition of receptor-mediated cation influx
      by tolfenamic acid, the agonist induced Mn2+ influx was studied in Ca2+ free
      medium. Tolfenamic acid (10-30 microM) reduced fMLP-stimulated Mn2+ influx in
      neutrophils in a concentration-dependent manner. The simultaneous Ca2+ release
      from intracellular stores was not affected. Protein kinase C activity in
      sonicated human neutrophils and the purified enzyme from rat brain were inhibited
      by the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2
      methylpiperazine) but not by tolfenamic acid. Both failed to inhibit neutrophil
      degranulation induced by phorbol myristate acetate, a protein kinase C activator.
      Tolfenamic acid (100 microM) increased the cellular cAMP levels up to 1.3-fold in
      the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. No
      effects on cellular cGMP levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549644
TI  - Anti-oxidant actions of oxymethazoline and xylomethazoline.
AB  - Anti-oxidant actions of oxymethazoline and xylomethazoline were investigated by
      measuring inhibition of microsomal lipid peroxidation and hydroxyl radical
      scavenging activity. Oxymethazoline was shown to be a potent inhibitor of lipid
      peroxidation (IC50 = 4.9 microM at t = 15 min, IC50 = 8.1 microM at t = 30 min),
      in contrast to xylomethazoline. Both compounds were excellent hydroxyl radical
      scavengers. Their rate constants (ks = 1.1 x 10(12) M-1 s-1 for oxymethazoline
      and ks = 4.7 x 10(10) M-1 s-1 for xylomethazoline) exceeded the rate constant of
      a known powerful scavenger cimetidine (ks = 1.8 x 10(10) M-1 s-1). The difference
      in inhibiting lipid peroxidation might be explained by the fact that only
      oxymethazoline has a hydroxy group which can donate a hydrogen atom and terminate
      the chain reaction of lipid peroxidation. The mechanism of hydroxyl radical
      scavenging activity is still unclear. Moreover oxymethazoline seems to have a
      different mode of action in scavenging hydroxyl radicals than xylomethazoline and
      cimetidine which results in an extremely high rate constant. Because oxidants
      play a role in tissue damage in inflammation, it was hypothesized that especially
      oxymethazoline and to a lesser extent xylomethazoline may have an additional
      beneficial effect, due to their anti-oxidant properties, in the topical treatment
      of nasal inflammation.

PMID- 8549645
TI  - Endothelin-1, but not endothelin-3, suppresses lipoprotein lipase gene expression
      in brown adipocytes differentiated in culture.
AB  - The effect of endothelins on lipoprotein lipase activity and lipoprotein lipase
      mRNA levels was studied in brown adipocytes differentiated in culture.
      Lipoprotein lipase activity was determined in two fractions; lipoprotein lipase
      released by heparin (10 IU/ml, 1 h) into the medium (heparin-releasable fraction)
      and lipoprotein lipase activity remaining in cells (extractable fraction). Time
      course studies showed that endothelin 1 (10(-7) M) progressively decreased both
      lipoprotein lipase fractions (heparin-releasable, extractable), until nadir at 24
      h. Endothelin-1 reduced both lipoprotein lipase activities (heparin-releasable,
      extractable) in a concentration-dependent manner, whereas endothelin-3 did not
      produce any significant changes in either of them. Northern blot analysis
      revealed that endothelin-1 (10(-7)-10(-11) M) caused a concentration-dependent
      decrease in lipoprotein lipase mRNA obtained from cells on day 9. Furthermore,
      pretreatment of brown adipocytes with endothelin ETA receptor antagonist FR139317
      antagonized the endothelin-1-induced reduction of lipoprotein lipase activity and
      lipoprotein lipase mRNA. These results suggest that endothelin-1 decreases
      lipoprotein lipase activity by inhibiting the lipoprotein lipase gene expression
      in brown adipocytes differentiated in culture, possibly through endothelin ETA
      receptors on cell membranes. Because of marked reduction of lipoprotein lipase
      activity and its mRNA as a marker of adipogenic differentiation, endothelin-1 may
      have an inhibitory role in the differentiation of brown adipocytes.

PMID- 8549646
TI  - Dual effect of muscarinic receptor agonists on Ca2+ mobilization in SH-SY5Y
      neuroblastoma cells.
AB  - The muscarinic receptor-stimulated mobilisation of calcium ions in SH-SY5Y
      neuroblastoma cells was measured as function of the concentration of seven
      muscarinic receptor agonists and partial agonists: carbamoylcholine,
      acetylcholine, propionylcholine, butyrylcholine, acetylthiocholine,
      methylfurmethide and tetrametylammonium. The dose-response curves reached a clear
      maximum followed by a downturn of the curve. The concentration interval where the
      activatory and inhibitory effects occurred depended on the structure of the
      ligand. The bell-shaped dose-response curves were analysed assuming that the
      drugs interact with two sites, which are responsible for agonistic and
      antagonistic effects, on the muscarinic receptors. The results indicate that full
      vs. partial agonism is at least in part determined by relative affinities of
      these two sites.

PMID- 8549647
TI  - Expression and characterization of the substance P (NK1) receptor in the rat
      pituitary and AtT20 mouse pituitary tumor cells.
AB  - Although substance P is known to take part in the regulation of the anterior
      pituitary, no conclusive evidence for the expression of the tachykinin NK1
      receptor has been found yet in the pituitary or pituitary derived cells. With the
      reverse transcription-polymerase chain reaction (RT-PCR) method we could detect
      the low abundant transcripts of the NK1 receptor in the rat pituitary and in the
      AtT20 cell line (clone D16v). Furthermore, the functional expression of the NK1
      receptor in AtT20 cells was confirmed by activation of the phosphatidylinositol
      calcium second messenger system when the cells were treated with substance P. In
      addition, binding studies also indicated the functional expression of this
      receptor in AtT20 cells. Thus we provide the first evidence that the NK1 receptor
      is expressed in AtT20 cells and the rat pituitary.

PMID- 8549648
TI  - Ketanserin and ritanserin discriminate between recombinant human 5-HT1D alpha and
      5-HT1D beta receptor subtypes.
AB  - Compounds able to discriminate functionally between the closely related cloned
      human 5-HT1D alpha and 5-HT1D beta receptor subtypes have not been reported
      previously. In [3H]5-HT competition assays, the classical 5-HT2A receptor
      antagonists, ritanserin and ketanserin, displayed moderate affinity (pKi = 7.30
      and 7.17, respectively) and marked selectivity (22- and 71-fold, respectively)
      for the recombinant human 5-HT1D alpha subtype relative to the 5-HT1D beta
      receptor. In contrast, the nonselective 5-HT1/2 receptor antagonist,
      methiothepin, exhibited similar binding affinities (pKi = 7.64-8.01) for both
      recombinant 5-HT1D subtypes. The antagonistic properties of these compounds were
      evaluated for their ability to block 5-HT-induced inhibition of forskolin
      stimulated cAMP accumulation in intact cells stably expressing either 5-HT1D
      alpha or 5-HT1D beta receptors. All three compounds behaved as antagonists devoid
      of intrinsic activity in the functional assays. The apparent pKb values
      determined in functional assays closely matched their pKi values obtained in
      binding assays. Since ketanserin exhibits significant selectivity for the human 5
      HT1D alpha receptor, this antagonist can be used as a pharmacological tool to
      discriminate between 5-HT1D alpha and 5-HT1D beta receptor-mediated responses in
      human tissues.

PMID- 8549649
TI  - Regulation of CCAAT/enhancer binding protein isoforms by serum and
      glucocorticoids in the rat intestinal epithelial crypt cell line IEC-6.
AB  - Members of the CCAAT/enhancer binding protein (C/EBP) gene family are expressed
      in murine intestine. However, little is known about their regulation in
      intestinal epithelial cells. In an attempt to determine regulatory mechanisms
      involved in their expression, we examined C/EBP alpha, beta, and delta isoform
      expression in response to serum and glucocorticoids in the rat intestinal
      epithelial crypt-derived cell line IEC-6, by Northern blot, transcription run-on
      assays, indirect immunofluorescence, Western blot, and electrophoretic mobility
      shift assays. Serum leads to rapid and transient increases in C/EBP alpha and
      beta mRNA and protein levels by posttranscriptional regulatory mechanisms,
      without affecting transcriptional initiation. However, C/EBP-specific DNA binding
      capacity is not affected by serum. Whereas C/EBP alpha expression is not
      regulated by glucocorticoids, C/EBP beta and delta mRNA and protein levels are
      rapidly induced. These inductions result from both increased transcription rates
      and posttranscriptional regulatory mechanisms as well. Moreover, C/EBP beta and
      delta containing DNA binding complexes are increased by glucocorticoids as
      determined by supershift assays, in contrast to C/EBP alpha containing complexes.
      Immunofluorescence studies show cytoplasmic and nuclear localization for C/EBP
      alpha, in contrast to a restricted nuclear localization for both C/EBP beta and
      C/EBP delta. These results confirm C/EBP isoforms expression in intestinal
      epithelial cells. Differential regulation by serum and glucocorticoids as well as
      different localization of three C/EBP isoforms suggest a role for this class of
      transcription factors in the control of gene expression in intestinal epithelial
      cells.

PMID- 8549650
TI  - The role of phosphorylation in modulating beta 1 integrin localization.
AB  - The beta 1-integrin subunit localizes to focal contacts during F9 teratocarcinoma
      stem cell differentiation to parietal endoderm. Concomitantly, this integrin
      subunit becomes dephosphorylated at serine 790, the only serine in the well
      conserved cytoplasmic domain of beta 1. We hypothesized that this
      dephosphorylation is required for this subunit to move to a focal contact. To
      test this, we transfected F9 stem cells with distinct cDNAs encoding three forms
      of chicken beta 1: the wild-type, and two site-specific mutants possessing amino
      acid substitutions at residue 790 which included methionine and aspartate. The
      negatively charged aspartate was selected to mimic the phosphorylated serine
      found at position 790 in the wildtype protein but in a form that cannot be
      dephosphorylated upon differentiation. The chicken beta 1 subunits
      heterodimerized with endogenous mouse alpha subunits and, using a chicken beta 1
      specific monoclonal antibody, we examined movements of these chimeric integrins
      to focal contacts using immunofluorescence microscopy. The chimeric integrins
      possessing either the wildtype or methionine mutant beta 1 subunits localized to
      focal contacts upon F9 differentiation. In contrast, the aspartate chimeric
      integrins failed to localize. These data suggest that the dephosphorylation of
      serine 790 is required for the beta 1 subunit to localize to focal contacts
      during F9 differentiation.

PMID- 8549651
TI  - Modulation of sensitivity to transforming growth factor-beta 1 (TGF-beta 1) and
      the level of type II TGF-beta receptor in LNCaP cells by dihydrotestosterone.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) and androgen are potential
      physiological regulators of prostate cancer cells. In the present study, we have
      used LNCaP cells as a model of androgen-responsive prostate cancer to investigate
      the effects of dihydrotestosterone (DHT) on the sensitivity to TGF-beta 1. The
      ability of LNCaP cells to respond to TGF-beta has been controversial. In some
      studies, LNCaP cells were insensitive to TGF-beta 1 while, in others, they were
      sensitive to the growth inhibitory effect of TGF-beta 1. The present study was
      carried out to establish androgenic conditions that rendered LNCaP cells
      sensitive to TGF-beta 1. Cells were cultured in phenol-red-free RPMI 1640 medium
      supplemented with 10% charcoal-stripped fetal bovine serum. DHT was added at the
      following concentrations: 0, 10(-12), 10(-10), and 10(-7) M. These concentrations
      were selected because they represent the zero DHT control, the low-proliferative
      dose, the high-proliferative dose, and the growth-arrest dose, respectively. The
      effects of TGF-beta 1 observed on LNCaP cells included inhibition of cell
      proliferation, decrease in cell viability, alteration in cell morphology, and
      enhancement of gene transcriptional activity through activation of a TGF-beta
      responsive promoter. Of the various DHT concentrations investigated in this
      study, these effects of TGF-beta 1 on LNCaP cells were consistently demonstrated
      only at 10(-10) M. At other concentrations, the effects of TGF-beta 1 were either
      minimal or undetectable. Accompanying these effects of TGF-beta 1, a low but
      statistically significant level of TGF-beta 1-specific binding and an increased
      protein level of TGF-beta receptor type II were detected by a competitive binding
      assay and Western blot analysis respectively. These results indicate that LNCaP
      cells can be induced by DHT to respond to TGF-beta 1 and that DHT modulates the
      sensitivity to TGF-beta 1 and the level of TGF-beta receptor type II in these
      cells.

PMID- 8549652
TI  - Differential regulation of fibulin, tenascin-C, and nidogen expression during
      wound healing of normal and glucocorticoid-treated mice.
AB  - Expression and distribution of fibulins, nidogen, and tenascin-C were analyzed in
      healing skin wounds of normal and dexamethasone-treated mice. In normal mice both
      tenascin-C and fibulin-2 showed a marked increase in mRNA expression, which
      declined to normal levels after completion of skin repair. These two matrix
      proteins are found throughout the granulation tissue and persisted there after
      mRNA expression had ceased. Fibulin-1 is present in normal skin and in wounds but
      is not distinctly upregulated during the healing process. Nidogen, however, is
      expressed uniformly throughout the granulation tissue early in wound healing, has
      a peak expression around Day 7, and selectively localizes to basement membranes
      after healing is accomplished. Dexamethasone treatment led to a decreased
      expression of tenascin-C in healing wounds but had no effect on fibulin-2
      expression. In vitro experiments revealed that growth factors like TGF-beta 1 can
      partly counteract glucocorticoid action. These data therefore provide some
      molecular interpretations for the well-known glucocorticoid suppression of wound
      healing. They also indicate that repair involves complex regulatory processes
      which are obviously different for each of the four proteins studied.

PMID- 8549653
TI  - Reactive oxygen species act at both TGF-beta-dependent and -independent steps
      during induction of apoptosis of transformed cells by normal cells.
AB  - We have recently shown that TGF-beta-treated normal fibroblasts can induce
      apoptosis of transformed cells. The overall process was inhibited by antioxidants
      and radical scavengers, pointing to a role of reactive oxygen species (ROS). To
      define the ROS-dependent steps precisely, our experimental system was dissected
      into three phases. During phase I, TGF-beta 1 induced production and release of
      apoptosis-inducing signal molecules by normal cells. In phase II, these signal
      molecules were transferred between normal and transformed cells. During phase
      III, transformed cells went into apoptosis. The use of antibody directed against
      TGF-beta revealed that TGF-beta was required only during phase I. Application of
      radical scavengers and antioxidants at defined phases revealed that reactive
      oxygen species are involved specifically with biochemical processes induced by
      TGF-beta in normal cells and early in signal transfer between normal cells and
      transformed cells. These data therefore point to a functional role of reactive
      oxygen species both for the TGF-beta 1-induced signal pathway in normal cells and
      for the induction of apoptosis in transformed cells.

PMID- 8549655
TI  - Delayed glucocorticoid-dependent development of the insulin response after heat
      shock in cultured fetal hepatocytes: correlation with a transient defect in
      glucocorticoid receptor binding property.
AB  - The effects of a mild heat shock were investigated on glucocorticoid-induced
      maturation of the insulin glycogenic response and on glucocorticoid receptor (GR)
      in cultured 15-day-old fetal rat hepatocytes. In all experiments, cell heating at
      42.5 degrees C from 30 to 90 min was applied at Day 1 of culture before exposure
      to glucocorticoids. In never heated cells, the insulin stimulation of
      glycogenesis, measured bh [14C]glucose incorporation into glycogen for 3 h,
      developed to be maximal after 32 h in the presence of 100 nM dexamethasone (2.4
      fold). In cells preheated at 42.5 degrees C for times equal to or greater than 60
      min before being returned to 37 degrees C in dexamethasone-containing medium, the
      insulin response was not seen after 32 h (1.3-fold versus 2.4-fold) but was
      clearly expressed after 48 h. Heat treatment induced a progressive decrease in
      intact cell GR binding, reaching 40% after 1 h. When cells were returned to 37
      degrees C, GR binding following a lag time of 8 h increased up to complete
      restoration after 24 h. Such heat shock-induced variations affected the number of
      GR binding sites with little change in GR binding affinity, while no
      modifications were seen in the 97-kDa GR level from whole cell extracts as
      revealed by Western immunoblotting using an anti-GR antibody (BuGR2).
      [35S]Methionine metabolic labeling showed a reversible heat-stimulated synthesis
      of 70- and 90-kDa heat shock proteins (Hsps). Variations in Hsp90 level revealed
      by Western immunoblotting using an anti-Hsp90 antibody (AC88) were inversely
      correlated with time with GR binding. Therefore, a mild heat shock applied to
      cultured fetal hepatocytes led to a delayed development of the glycogenic
      response to insulin linked to a defect in GR binding property with no alteration
      in the GR protein level.

PMID- 8549654
TI  - PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in
      rat smooth muscle cells.
AB  - Vascular smooth muscle cells (VSMC) are the predominant cell type in the media of
      a normal artery. Injury to the vessel wall leads to platelet deposition and the
      release of numerous factors, including PDGF, which exerts its biological effects
      by binding to specific surface receptors on the smooth muscle cell membrane. We
      demonstrate that PDGF-stimulated smooth muscle cells activate the STAT (signal
      transducers and activators of transcription) family of proteins in addition to
      other signaling pathways (e.g., RAS-RAF-MAP Kinase). We show that the
      transcription factor p91 (STAT1 alpha) is rapidly activated by PDGF in VSMC and
      specifically binds to the regulatory elements SIE or GAS. We hypothesize that
      signal transduction by p91 plays an important role in VSMC, especially after
      injury with the release of growth factors such as PDGF.

PMID- 8549656
TI  - Laminin-1 selectively stimulates neuron generation from cultured retinal
      neuroepithelial cells.
AB  - Signals derived from the extracellular matrix (ECM) largely influence neuron
      differentiation and development. However, the action of specific ECM components
      in these processes is poorly understood. This had led us to investigate the role
      of different laminins in the survival, proliferation, and neuron differentiation
      of cultured neuroepithelial cells from the developing chicken retina. Dissociated
      retinal neuroepithelial cells from 5-day-old chicken embryos, cultured on laminin
      1, survived, proliferated, and differentiated into neurons, as assessed by both
      [3H]-thymidine uptake and acquisition of neuronal markers. Nevertheless, these
      effects took place only in the presence of cell-cell contact. In contrast, RN22
      Schwannoma-derived laminin (devoid of alpha 1 chain) and merosin (bearing an
      alpha 2 chain), which also promoted proliferation when cell-cell contact
      occurred, led to reduced cell survival and failed to foster neuron
      differentiation. Furthermore, the laminin-1 P1 fragment (containing the rod-like
      portions of the short arms of the molecule) also failed to support neuron
      generation. In contrast, the laminin-1 E8 fragment (containing the long arm of
      the molecule) supported such a process to the same extent as the whole laminin-1
      molecule, although a similar activity cannot be ruled out in other globular
      domains of the short arms. However, these results stress the importance of the
      carboxy-terminal part of alpha 1 chain in neuronal development. A cDNA fragment
      of a chicken alpha 1 chain was cloned and semiquantitative PCR amplification
      revealed that its mRNA is expressed in retinal neuroepithelial cells at the time
      of neuron differentiation. Our data strongly suggest that an alpha 1-like chain
      containing laminin is needed for differentiation of neuron precursor cells.

PMID- 8549657
TI  - Differential regulation of collagenase and stromelysin mRNA in late passage
      cultures of human fibroblasts.
AB  - Nontransformed human fibroblast cell cultures have been extensively studied as an
      in vitro model for cellular senescence. Recently there has been considerable
      interest in using the human fibroblast in the identification of genes relevant to
      the process of replicative senescence. We demonstrated that in comparison with
      early passage cultures the expression of collagenase and stromelysin mRNAs and
      proteins was increased > 8 x in late passage cultures of human fibroblasts and,
      in addition, expression of Il-1 alpha, a cytokine that regulates collagenase and
      stromelysin expression, was also significantly increased in late passage cell
      cultures. These findings suggested the hypothesis that constitutive Il-1 alpha
      expression in late passage cells may coordinately regulate the age-associated
      increase in the expression of collagenase and stromelysin. To test this
      hypothesis we examined the effects of long-term Il-1 alpha treatment, serum
      starvation, and cycloheximide inhibition on collagenase and stromelysin mRNA
      levels in early and late passage human fibroblast cell cultures. Here we report
      that in late passage cell cultures, collagenase and stromelysin mRNAs respond
      differentially to Il-1 alpha, serum starvation, and cycloheximide addition.
      Continuous exposure to Il-1 alpha reduced the half-life of stromelysin mRNA but
      had little effect on the half-life of collagenase mRNA. In contrast to
      stromelysin, the collagenase mRNA level is dependent on serum factors.
      Collagenase is induced during recovery from cycloheximide inhibition, but
      stromelysin expression is not affected. These results establish that collagenase
      and stromelysin mRNAs are differentially regulated in both early and late passage
      human fibroblasts and suggest that the mechanisms responsible for the age
      associated increase in the two mRNAs are different. In addition, these studies
      support the conclusion that continuous long-term exposure to Il-1 alpha, a
      condition that is characteristic of late passage cells, is not the factor
      responsible for the high levels of collagenase expression, but may be critical
      for stromelysin expression.

PMID- 8549658
TI  - Metabolic fluxes regulate the success of sporulation in Saccharomyces cerevisiae.
AB  - In this work we investigated to what extent cellular metabolism and energetics
      regulate sporulation in Saccharomyces cerevisiae and which metabolic pathways are
      involved in such regulation. Sporulation, meiosis, and associated metabolic
      fluxes in S. cerevisiae strain CH1211 were studied in several experimental
      protocols involving changes of carbon source (acetate, lactate, or pyruvate) or
      cell density in sporulation medium, or changing the phase of batch growth at
      which cells were harvested before transfer to sporulation medium. In acetate
      based sporulation medium, the rate at which cells utilized glyoxylate and
      gluconeogenic pathways correlated positively with the percentage of asci per cell
      at 72 h. In contrast, in lactate sporulation medium the frequency of sporulation
      correlated negatively with both the rate of lactate consumption and the fluxes
      through gluconeogenesis and the pyruvate-carboxylase catalyzed step. In the
      presence of lactate, the respiratory capacity did correlate positively with the
      percentage of asci per cell. The experimental data suggest that acetate limits
      fluxes to anabolic precursors during sporulation. In contrast, sporulation on
      lactate appears to be influenced by catabolic processes or, even more precisely,
      by the respiratory capacity of yeast cells. The results obtained are discussed in
      terms of the hypothesis that an imbalance between anabolic and catabolic fluxes
      may be required for an efficient sporulation.

PMID- 8549659
TI  - Immunoelectron microscopic localization of the 60-kDa heat shock chaperonin
      protein (Hsp60) in mammalian cells.
AB  - The subcellular distribution of the 60-kDa heat shock protein (Hsp60) was
      examined in a variety of mammalian cells and tissues, including Chinese hamster
      ovary cells, human fibroblasts, B-SC-1 kidney cells, Daudi Burkitt's lymphoma
      cells, and rat liver, by immunogold electron microscopy employing six different
      monoclonal and polyclonal antibodies that are specific for Hsp60. In cryosections
      or LR Gold sections of different cultured cells, intense labeling of mitochondria
      was obtained, typically 200-500 gold particles per mitochondrion and accounting
      for 80-85% of the total gold particles. In addition, however, in all cell types
      and using all of the antibodies, about 15-20% of the labeling due to Hsp60 was
      seen at discrete extramitochondrial sites. Such sites included those in close
      proximity to mitochondrial outer membranes, foci on endoplasmic reticulum, on the
      cell surface, and in unidentified vesicles. In cryosections of rat liver,
      specific labeling due to Hsp60 antibodies was also observed within peroxisomes.
      Labeling of all cellular components by these antibodies could be prevented by
      preadsorption with purified recombinant mitochondrial Hsp60 indicating that the
      labeling is specific for Hsp60. Biotin labeling of cell surface proteins results
      in biotinylation of Hsp60 as analyzed by immunoprecipitation and Western blots,
      providing further evidence for Hsp60 presence on the plasma membrane.
      Immunoprecipitation experiments with Hsp60 antibodies show that under normal
      conditions no detectable precursor Hsp60 protein is present in cells. However, in
      cells treated with the potassium ionophore nonactin, which blocks mitochondrial
      import, only the precursor form of Hsp60 accumulates, providing evidence that at
      least partial mitochondrial import of Hsp60 is necessary for its maturation.
      These results also provide evidence that no other 60-kDa protein other than
      mitochondrial Hsp60 is recognized by the antibodies used for electron microscopy.
      These findings raise interesting questions concerning the possible role of Hsp60
      at extramitochondrial sites.

PMID- 8549660
TI  - Effects of depletion of intracellular tetrahydrobiopterin in murine
      erythroleukemia cells.
AB  - The biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH4) in murine
      erythroleukemia (MEL) cells is almost completely inhibited by 10 mM, 2,4-diamino
      6-hydroxypyrimidine (DAHP), which targets GTP cyclohydrolase. The inhibition
      results in dephosphorylation of the retinoblastoma gene product, prolongation of
      the G1-phase in the cell cycle, and subsequent commitment to terminal
      differentiation of MEL cells. Reversal of the processes by repletion of cellular
      BH4 with biopterin-related compounds including BH4, 7,8-dihydrobiopterin (7,8
      BH2), sepiapterin, and 7,8-dihydroneopterin has generated complicated results.
      Low micromolar exogenous pterin compounds had little or no effect. At 300 microM
      or higher, the synthesis of hemoglobin by DAHP-induced MEL cells is significantly
      inhibited by 7,8-dihydrobiopterin and sepiapterin. However, further cell cycle
      analysis shows that the inhibition of cell differentiation by 7,8-BH2 and
      sepiapterin may not be due to the reversal of cell proliferation. Inhibition of
      BH4 biosynthesis in MEL cells by inhibitors of sepiapterin reductase has also
      been studied. None of the inhibitors that were tested, including N-chloroacetyl
      dopamine and N-acetylserotonin, which are specific for sepiapterin reductase, can
      block MEL cells in G1-phase or induce the cells to commit to terminal
      differentiation. Furthermore, inhibitors of sepiapterin reductase are found to
      reduce or to abolish hemoglobin synthesis in differentiating MEL cells induced by
      hexamethylene bisacetamide. The mechanism for this is not clear. Not all of the
      effects caused by the depletion of BH4 synthesis can be rescued by repletion of
      BH4. These results suggest that BH4 may not regulate proliferation or
      differentiation of MEL cells as previously thought. Its function in MEL cells is
      still not clear.

PMID- 8549661
TI  - In situ localization of nucleolin in the plant nucleolar matrix.
AB  - The analysis of isolated nucleolar matrices from onion cells by light and
      electron microscopy, 2-D separation of proteins, and confocal microscopy has
      confirmed the existence of an organized nucleolar matrix with a complex protein
      composition to which are attached the insoluble processing complexes. In the
      present work, we present evidence from immunoblotting, immunofluorescence,
      immunogold labeling, and preferential cytochemical staining with bismuth salts
      that an insoluble fraction of the multifunctional protein nucleolin, is a
      component of the onion nucleolar matrix, and analyse its ultrastructural
      distribution in the described domains of the matrix.

PMID- 8549662
TI  - Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon
      adenocarcinoma cells: effects on cell cycle and apoptosis.
AB  - Aspirin and other NSAIDs reduce the incidence of and mortality from colon cancer,
      but their mechanism of action remains unknown. We evaluated the effect of aspirin
      (ASA) and three other structurally unrelated NSAIDs (indomethacin, naproxen, and
      piroxicam) on cell proliferation, cell cycle phase distribution, and the
      development of apoptosis in HT-29 colon adenocarcinoma cells in vitro. All of the
      NSAIDs examined reduced the proliferation and altered the morphology of these
      cells in a time- and concentration-dependent manner. In addition, they altered
      the cell cycle phase distribution of these cells. They increased the proportion
      of cells in the G0/G1 phase and reduced the proportion in the S phase of the cell
      cycle. ASA and indomethacin also reduced the percentage of cells in the G2/M
      phase, whereas naproxen and piroxicam did not. Parallel to their effect on cell
      cycle, ASA and indomethacin also reduced the levels of p34cdc2 and p33cdk2, two
      cyclin-dependent kinases that are important for cell cycle progression. Finally,
      all the NSAIDs analyzed, except ASA, induced apoptosis in these cells. There as a
      rough correlation between the relative potency of these compounds in inducing
      apoptosis and their effectiveness in retarding cell proliferation. Our findings
      indicate that NSAIDs can reduce the proliferation of HT-29 colon cancer cells in
      vitro. In addition, they cause cell cycle quiescence and apoptosis, both of which
      could account for their anti-proliferative effect. These findings suggest
      possible mechanisms for the cancer preventive effects of these compounds in
      humans.

PMID- 8549663
TI  - Inductive influences of epimorphin on endothelial cells in vitro.
AB  - Epimorphin is known as a mesenchymal factor involved in epithelial morphogenesis.
      This protein has, however, a curious nature in that only certain of its molecules
      are transported to extracellular regions after having undergone complex
      conformational changes. In the present study, we generated an N-terminally
      modified recombinant epimorphin fragment as a substitute for the extracellular
      epimorphin and examined n detail how this polypeptide affects cellular behavior
      in a model cell system. As immunohistochemical studies revealed that epimorphin
      is abundant in regions close to endothelial cells in venulae, we chose
      endothelial cells as the model cell and investigated the influence of this
      polypeptide on their cellular behavior in vitro. The recombinant epimorphin
      guided the endothelial cells to align themselves in tandem and to present a
      branched morphology in the three-dimensional culture system. We also discovered
      that the endothelial cells were induced to secrete several cytokines, including
      those involved in angiogenesis, and were suppressed in terms of proliferation by
      this molecule. These results suggest that epimorphin has a regulatory role in the
      activation of endothelial cells and is active in supporting the resulting
      cellular arrangement.

PMID- 8549664
TI  - Annexin VII relocalization as a result of dystrophin deficiency.
AB  - Annexin VII (synexin) is a member of the annexin family of proteins, which are
      characterized by Ca(2+)-dependent binding to phospholipids. In normal skeletal
      muscle annexin VII is located preferentially at the plasma membrane and the t
      tubule system [Selbert et al. (1995) J. Cell. Sci. 108, 85-95]. Here we have
      analyzed the distribution of annexin VII in muscle disorders in which the Ca2+
      regulation is affected. A remarkable difference was observed in muscle specimens
      from patients suffering from Duchenne muscular dystrophy and also in muscle from
      the MDX mouse where annexin VII was gradually released from the sarcolemmal
      membrane into the cytosol and into the extracellular space during progression of
      the disease. Hypercontracted muscle fibers positive in Ca2+ staining were devoid
      of cytosolic annexin VII. Annexins IV and VI were similarly released into the
      extracellular space. Whereas normal skeletal muscle showed specifically the 51
      kDa annexin VII isoform, in dystrophic muscle different ratios of the 51-kDa and
      the muscle-atypic 47-kDa isoforms were observed. The potential of annexin VII to
      serve as a tool with which cellular Ca2+ levels can be studied and different
      muscular disorders classified is discussed.

PMID- 8549665
TI  - TGF-beta 1-stimulated adhesion of human mononuclear phagocytes to fibronectin and
      laminin is abolished by IFN-gamma: dependence on alpha 5 beta 1 and beta 2
      integrins.
AB  - Monocyte migration within the extravascular space of inflamed tissues is
      controlled by adhesion molecules and inflammatory cytokines. In this study, we
      analyzed the capacity of TGF-beta 1 and IFN-gamma to regulate adhesion of human
      activated monocytes to fibronectin (FN) and to laminin (LM), two components of
      the extracellular matrix. When cultured in the absence of any of these two
      stimuli, human monocytes underwent "spontaneous activation" and adhered to both
      FN and LM. Adhesion to FN was inhibited in the presence of alpha 5 and beta 1
      integrin blocking antibodies, whereas beta 2 blocking antibody blocked attachment
      to LM. Exogenous TGF-beta 1 increased the adhesive ability of monocytes to FN and
      to LM, respectively, linked to the increase of alpha 5 and beta 2 mRNA and
      protein synthesis levels. Moreover, an increase in alpha 5 expression at the
      monocyte cell surface was observed. In contrast, monocytes stimulated with
      exogenous IFN-gamma lost their capacity to bind to FN and this coincided with the
      down-regulation of surface alpha 5 expression which occurred at the
      posttranscriptional level of alpha 5 synthesis. Although IFN-gamma-treated
      monocytes also showed a decreased ability to adhere to LM, no alteration of beta
      2 mRNA levels, beta 2 protein synthesis, and beta 2 cell surface expression was
      detectable, thus suggesting a modification of the functional state of surface
      beta 2 integrins. Furthermore, when stimulated with TGF-beta 1, IFN-gamma
      pretreated monocytes reacquired the ability to bind to FN and LM. Conversely, IFN
      gamma reduced adhesiveness to FN and LM of monocytes initially stimulated with
      TGF-beta 1. These in vitro adhesive-deadhesive responses of monocytes to TGF-beta
      1 and IFN-gamma modulation may reflect mononuclear phagocyte motility within
      sites of inflammation.

PMID- 8549666
TI  - Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines:
      dimethyl sulfoxide inhibits IL-6-induced differentiation of SKW6-CL4 into IgM
      secreting plasma cells.
AB  - We have previously found that dimethyl sulfoxide (DMSO), a known inducer of
      differentiation in several kinds of myeloid cells, arrests proliferation of human
      lymphoid cells including Raji and Akata Burkitt's lymphoma cells at the G1 phase.
      We investigated whether DMSO affects cell proliferation and differentiation of
      the lymphoid cell line SKW6-CL4, which is capable of differentiating terminally
      into IgM-producing cells. As in the case of Raji, Akata, and Molt-4, the
      proliferation of SKW6-CL4 was reversibly arrested at the G1 phase by treatment
      with 2% DMSO for 5 days even in the presence of interleukin-6 (IL-6). DMSO
      inhibited spontaneous IgM secretion as well as IL-6-induced IgM production in
      SKW6-CL4 at a concentration lower than that affecting cell proliferation. Of the
      cell-surface differentiation markers CD10, CD20, CD21, and CD23, the expression
      of CD20 was suppressed by DMSO treatment, and partial restoration of the
      expression was observed 24 to 48 h after release from DMSO. The level of IL-6
      receptor protein was not affected by DMSO treatment. These results indicate that
      DMSO not only arrests the cell cycle of a human lymphoid cell line SKW6-CL4 at
      the G1 phase but also inhibits the differentiation into IgM-secreting cells at a
      concentration lower than that affecting cell proliferation and that DMSO
      overcomes the effect of IL-6 on terminal differentiation of SKW6-CL4. As a whole,
      proliferation of human lymphoblastoid cell lines was revealed to be reversibly
      arrested at the G1 phase by DMSO, which is known to induce differentiation in
      several myeloid cells, without inducing cell differentiation.

PMID- 8549667
TI  - Identification and immunolocalization of laminin in cartilage.
AB  - In a previous study on the role of integrins in the interaction of human
      chondrocytes with extracellular collagen and fibronectin (Durr et al., (1993)
      Exp. Cell Res. 207, 235) we showed that chondrocytes adhere to laminin-1 (LN-1)
      in a beta 1-integrin-dependent manner. FACS analysis with various integrin
      antibodies including the monoclonal antibody GOH3 indicated the presence of the
      alpha 6 beta 1-laminin receptor on the chondrocyte surface. Anti-alpha 6
      antibodies inhibited adhesion to the LN-1/E8 fragment, but not to whole laminin
      or heat-denatured Laminin-1, indicating that chondrocytes utilize at least two
      beta 1-integrins for laminin adhesion, one of which is alpha 6 beta 1 recognizing
      the LN-1/E8 fragment. The presence of alpha 6 beta 1-integrin on the chondrocyte
      surface also suggested the existence of laminin-like molecules in cartilage. Here
      we provide immunological and biochemical evidence in support of this possibility.
      Several polyclonal antibodies raised against laminin-1 or the LN-1/E8 fragment
      revealed a strong pericellular reaction in sections of human fetal epiphyseal
      cartilage and adult articular cartilage. In the fetal epiphysis laminin staining
      was most prominent in mature, large chondrocytes appearing in the secondary
      ossification zone, in particular, in the vicinity of invading capillary sprouts.
      Chondrocytes in the proliferating and hypertrophic zone of the growth plate and
      perichondrium cells were negative. All chondrocytes that stained for alpha 6
      integrin also stained for laminin-1. A laminin-1-like molecule was extracted from
      hyaline cartilage with two bands migrating slightly faster than the alpha 1 and
      beta 1/gamma 1 subunits of laminin on SDS-gel electrophoresis. The two bands
      stained with anti-laminin-1 antibodies and could be immunoprecipitated with the
      same antibodies from metabolically labeled chondrocyte cultures. These findings
      suggests a role for laminin in developing cartilage and thus additional roles for
      laminins outside basement membranes.

PMID- 8549668
TI  - Intrathymic distribution of the two avian thymic parvalbumins.
AB  - Although parvalbumins are generally viewed as intracellular Ca2-
      buffers/transporters, avian species express two thymus-specific isoforms that may
      play alternative biological roles. These proteins, known as avian thymic hormone
      (ATH) and chicken parvalbumin 3 (CPV3), are conjectured to influence
      thymopoiesis. In this paper, we compare their intrathymic distributions. Isoform
      specific monoclonal antibodies against ATH and CPV3 were labeled with fluorescein
      and Cy5, respectively, and then used to probe paraffin sections of chicken thymus
      tissue. Confocal microscopy of the stained sections reveals that ATH and CPV3 are
      both confined to the thymic cortex and that they are frequently coexpressed by a
      subset of epithelial cells. However, their expression patterns are not completely
      superimposible. Cortical epithelial cells are also observed that stain for just
      one of the two avian parvalbumin isoforms, albeit at lower frequency.
      Significantly, a subset of cortical thymocytes exhibits peripheral staining for
      one or both of the proteins. This result may imply the existence of plasma
      membrane receptors for the two proteins on select T-cell precursors.
      Alternatively, it may signal low level expression of the thymic parvalbumins by
      the thymocytes population.

PMID- 8549669
TI  - SRB1, a class B scavenger receptor, recognizes both negatively charged liposomes
      and apoptotic cells.
AB  - Scavenger receptors mediate the recognition of a wide range of negatively charged
      macromolecules such as acetylated low-density lipoproteins (AcLDL). We previously
      reported the isolation of CHO cell variants expressing a novel type of scavenger
      receptor, distinct from type I and II macrophage scavenger receptors, that
      recognize both AcLDL and negatively charged liposomes. In the present study, we
      found that these isolated CHO cells express class B scavenger receptors (SRB1),
      which have recently been identified as a new member of the CD36 family of
      membrane proteins. The isolated CHO cells and CHO transfectants constitutively
      expressing SRB1 recognized and mediated the endocytosis of cells undergoing
      apoptosis as well as that of negatively charged liposomes. In contrast, CHO cells
      constitutively expressing type I or II scavenger receptors were unable to take up
      these ligands.

PMID- 8549670
TI  - Detection of apoptosis and DNA replication by differential labeling of DNA strand
      breaks with fluorochromes of different color.
AB  - Selective DNA strand break induction by photolysis (SBIP) at sites that contain
      incorporated halogenated nucleotides has been recently proposed as a means of
      analyzing DNA replication and detecting proliferating cells. The presence of
      numerous in situ DNA strand breaks is also an inherent feature of apoptotic
      cells. The aim of the present study was to differentially label DNA strand breaks
      in apoptotic cells vs photolysis-induced breaks in BrdUrd incorporating cells.
      This would allow one, by multicolor staining, to identify these respective cells
      in the same sample preparation. Toward this end, exponentially growing HL-60
      cells were pulse labeled with BrdUrd and then were subjected to hyperthermia or
      treated with DNA topoisomerase I inhibitor camptothecin to induce apoptosis. DNA
      strand breaks in apoptotic cells were first labeled directly with fluorochrome
      conjugated dUTP or dCTP, followed by dideoxynucleotide (to terminate chain
      elongation), in a reaction catalyzed by exogenous terminal deoxynucleotidyl
      transferase. The cells were subsequently exposed to UV light to photolyze DNA
      containing the incorporated BrdUrd. The photolysis-induced DNA strand breaks
      were, in turn, labeled with digoxygenin- or biotin-conjugated dUTP followed by
      digoxygenin antibody or avidin, respectively, conjugated with fluorochrome of
      another color. Alternatively, DNA strand breaks were labeled with BrdUTP which
      was then detected by FITC-conjugated anti-BrdUrd MoAb. Following counterstaining
      of cellular DNA with a fluorochrome of a third color it was possible to identify
      apoptotic cells, cells incorporating BrdUrd, and cells having no DNA strand
      breaks. Cell fluorescence was measured either by flow cytometry or with the
      microscope-based laser scanning cytometer. The SBIP approach also offers a
      possibility to study a colocalization of the immunocytochemically detectable cell
      constituents at the DNA replication points by microscopy. Using this approach the
      presence of the proliferating cell nuclear antigen at the DNA replication sites
      was revealed in MCF-7 breast carcinoma cells.

PMID- 8549672
TI  - Evidence that disruption of connexon particle arrangements in gap junction
      plaques is associated with inhibition of gap junctional communication by a
      glycyrrhetinic acid derivative.
AB  - Glycyrrhetinic acid exhibits many pharmacological activities, including the
      ability to block gap junctional communication. However, the mechanism of
      glycyrrhetinic action is not clear. Others have shown that glycyrrhetinic acid
      apparently binds to a single proteinatious binding site in the plasma membrane.
      We present evidence that while exposure to glycyrrhetinic acid derivatives may
      not affect protein synthesis or location, it does seem to alter connexon particle
      packing in gap junction plaques.

PMID- 8549671
TI  - Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or
      adipocytic differentiation of clonal murine target cells.
AB  - Osteogenic protein-1 (OP-1, BMP-7), a bone morphogenetic protein in the
      transforming growth factor-beta superfamily, induces endochondral bone formation
      in vivo, but the mechanism of action of OP-1 in osteogenesis is not yet
      established. Three murine clonal cell lines in different stages of
      differentiation exhibit graded responses to recombinant human OP-1: the mouse
      embryonal carcinoma ATDC5 cell, with potential for chondroblastic
      differentiation; the osteoblast-like MC3T3-E1 cell derived from mouse calvaria;
      and the multipotent fibroblastic C3H10T1/2 cell derived from mouse embryo
      connective tissue. We show that OP-1 acts on early stage mesenchymal progenitor
      cells (ATDC5, C3H10T1/2) to induce chondroblastic differentiation, while OP-1
      strongly enhances the osteoblastic phenotype of committed osteoblasts (MC3T3-E1),
      possibly explaining its induction of the endochondral ossification cascade in
      vivo. Markers of osteoblastic, chondroblastic, and adipocytic differentiation are
      compared. OP-1 is strongly mitogenic for ATDC5, showing dose-dependent (2.5-80
      ng/ml) induction of Alcian blue staining, alkaline phosphatase activity, and mRNA
      expression for collagen types II and IX, and matrix Gla protein. MC3T3-E1 cells
      do not proliferate or stain with Alcian blue in response to OP-1, but express
      elevated levels of alkaline phosphatase and osteocalcin. While low-dose OP-1
      treatment of C3H10T1/2 induces only adipocyte-like cells filled with lipid
      droplets, a high dose (500 ng/ml) causes the same cells to also exhibit
      chondrocytic properties. Thus, OP-1 can induce differentiation along elements of
      the endochondral ossification pathway according to the stage and potential of the
      target cell.

PMID- 8549673
TI  - A ribonucleotide reductase inhibitor, MDL 101,731, induces apoptosis and elevates
      TRPM-2 mRNA levels in human prostate tumor xenografts.
AB  - MDL 101,731, (E)2'-fluoromethylene-2'-deoxycytidine, is an irreversible inhibitor
      of ribonucleotide diphosphate reductase and causes regression of human tumors in
      nude mouse models. Messenger RNA levels for testosterone-repressed prostatic
      message-2 (TRPM-2), a transcript that increases in human tumor xenografts
      undergoing programmed cell death, were analyzed by in situ hybridization.
      Xenografts derived from a human prostate tumor cell line (PC-3) regressed
      following treatment with MDL 101,731 and the relative levels of TRPM-2 mRNA
      increased up to threefold in drug-treated animals. Apoptosis in the tumor
      xenografts was further indicated by in situ labeling of DNA strand breaks by
      incorporation of biotinylated-dUTP with terminal deoxynucleotidyl transferase. In
      vitro, PC-3 cells incubated with MDL 101,731 showed evidence of apoptosis based
      on flow cytometry and DNA laddering. These data support the hypothesis that MDL
      101,731 stimulates programmed cell death in regressing PC-3 xenografts.

PMID- 8549674
TI  - 1,25-dihydroxyvitamin D3 primes acute promyelocytic cells for TPA-induced
      monocytic differentiation through both PKC and tyrosine phosphorylation cascades.
AB  - NB4 cells are the only in vitro model of differentiation in acute promyelocytic
      leukemia (APL). Although these cells respond to all-trans-retinoic acid to form
      neutrophils, our group has recently shown that these cells are capable of
      terminal monocytic differentiation in response to combined treatment with 1,25
      dihydroxyvitamin D3 (1,25 D3) and 12-O-tetradecanoylphorbol-13-acetate (TPA). We
      show here that the agents need not be present simultaneously, but may be added
      sequentially. TPA treatment prior to 1,25 D3 led to the appearance of adherent
      cells; however, when 1,25 D3 treatment preceded TPA treatment cells expressed all
      differentiation markers reflective of terminal differentiation. This priming
      effect of 1,25 D3 was both dose and time dependent. Increasing the interval
      between 1,25 D3 and TPA treatment caused a decrease in this priming potential
      indicative of limited commitment inducing capacity of 1,25 D3. In order to
      characterize the mechanism of action of 1,25 D3 and TPA, chemical inhibitors of
      phosphorylation were used. Staurosporine and bisindolymaleimide GF 109203X
      treatment prior to and during 1,25 D3 treatment or TPA treatment caused
      attenuation of the differentiation response. Experiments utilizing tyrosine
      kinase and phosphatase inhibitors supported the hypothesis that 1,25 D3 signaling
      was mediated by both serine/threonine and tyrosine phosphorylation cascades.
      Results from this study provide evidence to support the hypothesis that 1,25 D3
      signaling occurs via nongenomic mechanisms which when combined with the signaling
      effects of TPA, allow for the terminal differentiation of APL cells. This model
      should be used to develop new differentiation therapies for APL and other
      leukemias.

PMID- 8549675
TI  - Myoblast fusion promotes the appearance of active protease nexin I on human
      muscle cell surfaces.
AB  - Protease nexin I (PNI) is a 43- to 50-kDa glycoprotein capable of inhibiting a
      number of serine proteases and belongs to the serpin superfamily. PNI is
      identical to glia-derived nexin, a neurite outgrowth promoter by virtue of its
      thrombin-inhibiting activity. Of particular relevance to neuromuscular biology
      and pathology, PNI was the first serpin shown to be highly localized to the
      neuromuscular junction and it maps to precisely the same locus as autosomal
      recessive amyotrophic lateral sclerosis (ALSJ) at chromosome 2q33-35. In the
      present report, we now show that in cultures of human skeletal muscle, PNI
      protein is expressed only after myoblast fusion into multinuclear myotubes and is
      localized in patches on their surfaces. We performed complex formation
      experiments with labeled thrombin, another target protease for PNI, with intact
      human muscle cells in culture. We detected specific SDS-stable PNI/thrombin
      complexes in myotube extracts only, indicating that active PNI was bound to their
      surfaces. We studied the gene expression of PNI mRNA using a 300-bp cDNA
      synthesized from the published sequence of human PNI. Confirming the protein
      data, upregulation of PNI appears in myotubes using Northern blot analysis. The
      current results reinforce the hypothesis that the regulation of the balance of
      serine proteases and serpins, such as PNI, is involved in muscle differentiation.
      They also prompt us to explore PNI abnormalities in several neuromuscular
      diseases, including ALSJ.

PMID- 8549676
TI  - Retinol binding protein and transthyretin are secreted as a complex formed in the
      endoplasmic reticulum in HepG2 human hepatocarcinoma cells.
AB  - Retinol binding protein (RBP), the retinol-specific carrier, circulates in blood
      as a 1:1 complex with the homotetrameric protein transthyretin (TTR). Both RBP
      and TTR are synthesized and secreted by the hepatocyte. In this work we have
      demonstrated, using HepG2 cells as a model system, that the association between
      the two proteins occurs inside the cell before secretion. The intracellular
      complex was detected only when metabolically labeled cells were lysed under mild
      detergent conditions (1.5% octylglucoside), followed by immunoprecipitation and
      SDS-PAGE. Alternatively, the immunoprecipitates from unlabeled cells lysed with
      the same buffer were analyzed by Western blotting. This finding was confirmed
      using the cross-linking agent dithiobis(succinimidyl) propionate before cell
      lysis. Moreover, we found that in cells treated with brefeldin A to block the
      exit of proteins from the endoplasmic reticulum (ER), the complex was present in
      the microsomal fraction. Thus, we can conclude that the RBP-TTR complex is formed
      inside the cell, more precisely within the ER. As RBP and TTR both lack an ER
      retention signal, we considered the possible involvement of chaperones in RBP and
      TTR retention in the ER and in complex formation. We found that calnexin, an ER
      integral membrane protein which functions as a chaperone, coprecipitates with RBP
      and TTR when cell lysis and immunoprecipitation are performed under mild
      conditions (1% Triton X-100). This result strongly suggests that calnexin may be
      involved in RBP and TTR retention in the ER, in TTR tetramer assembly, and
      possibly in complex formation.

PMID- 8549677
TI  - Functional heterogeneity of an isolated mitochondrial population revealed by
      cytofluorometric analysis at the single organelle level.
AB  - Isolated rat liver mitochondria were incubated under various metabolic conditions
      to determine their membrane potential (MMP) as measured continuously by a
      tetraphenylphosphonium (TPP+)-selective electrode. By flow cytometry, a parallel
      analysis of fluorescence emissions observing single mitochondria stained with the
      lipophilic cation 5,5',6,6'-tetrachloro-1,1'3,3'
      tetraethylbenzimidazolcarbocyanine iodide (JC-1) revealed linear correlation
      between the median orange fluorescence (FL2) due to J-aggregate formations and
      MMP values measured by TPP+. No correlation was detected with the green
      fluorescence (FL1) emission. A significantly higher correlation appeared between
      the FL2/FL1 ratio and MMP values. Within the same mitochondrial population,
      cytofluorimetric analysis revealed the presence of various classes of organelles
      with different MMP, whose distribution was dependent on metabolic condition. The
      highest functional heterogeneity was found in deenergized mitochondria, while the
      highest homogeneity was observed during the first phase of the phosphorylative
      process. Thus, these data suggest that the cytofluorimetric use of JC-1 provides
      direct experimental evidence for the hypothesis of functional mitochondrial
      heterogeneity, at least with respect to their membrane potential.

PMID- 8549678
TI  - Comparison of apoptosis signaling through T cell receptor, fas, and calcium
      ionophore.
AB  - The SUP-T13 cell line, a human T leukemia, is susceptible to apoptosis by various
      inducers, including anti-TCR mAb, calcium ionophores, and anti-fas mAb. Induction
      of apoptosis by these three agents was investigated, and several differences were
      found. All three agents induced DNA fragmentation with a similar time course, but
      the kinetics of cell death were different for the three agents. Anti-TCR mAb
      induced apoptosis, but not A23187- or anti-fas-induced apoptosis, was rescued by
      anti-CD3 mAb treatment. In contrast, only anti-fas mAb-mediated apoptosis was
      rescued by PKC activators such as PMA. These differences suggest that each of
      these three agents mediate apoptosis by unique signaling pathways. Nevertheless,
      two variant subclones of SUP-T13 were found to be resistant to all three
      apoptosis-inducing agents, suggesting a point(s) of common regulation between the
      different pathways. To determine whether this regulation occurred through bcl-2,
      p53, or c-myc, their expression in the parental and variant cells was determined.
      The three clones expressed approximately equal amounts of these proteins, and
      their levels did not change significantly upon treatment with anti-TCR or anti
      TCR plus anti-CD3 mAb. Thus, although the proximal signaling by various apoptosis
      inducers were quite different, a common mediator(s) (as yet unknown) may still
      regulate apoptosis induced by these multiple agents.

PMID- 8549679
TI  - Photoimmunotherapy of human uveal melanoma cells.
AB  - To examine whether tumor-reactive monoclonal antibodies can be used to enhance
      photodestruction of human uveal melanoma cells, we conjugated photosensitizer
      chlorin e6 monoethylenediamine monoamide (CMA) with a melanoma-reactive
      monoclonal antibody IG12 and evaluated the effectiveness of this immunoconjugate
      (IC) in the destruction of OCM431 human uveal melanoma cells in vitro. RPMI1846
      melanoma cells do not react with IC and were used as non-target cells. For
      control, target and non-target cells were treated with IC or light alone. The
      effects of IC and free CMA in the destruction of melanoma cells were compared.
      Cell survival was assessed by a colorimetric assay using tetrazolium salt MTT.
      Target (OCM431) cells preincubated with IC and irradiated with 5-40 J cm-2 showed
      light dose-dependent decrease in cell survival. At 40 J cm-2, OCM431 cells
      preincubated with IC showed only 6 +/- 1.4% viability. Under same treatment, non
      target (RPMI1846) cells showed much less phototoxicity; cell survival was 54 +/-
      2.1%. Treatment with free CMA and light at 40 J cm-2 showed similar phototoxicity
      to both target and non-target cells, with cell survival being 24.3 +/- 3.5% and
      23.7 +/- 1.5%, respectively. These results show that our IC is effective in
      causing photodestruction of human uveal melanoma cells in vitro. The
      phototoxicity is selective and more potent than free CMA.

PMID- 8549680
TI  - Optic nerve microvessels: a partial molecular definition of cell surface anionic
      sites.
AB  - Incorporated in the luminal glycocalyx of vascular endothelia (EC) are negatively
      charged microdomains (anionic sites). These sites are considered functionally
      important (a) in their interaction with circulating blood constituents, and (b)
      as a determinant of vascular permeability. The molecular composition of these EC
      sites, described for a number of tissues, has demonstrated a heterogeneity
      dependent on their anatomical location. Luminal anionic sites have not been
      characterized for EC of optic nerve. Optic nerves were removed from Sprague
      Dawley rats previously fixed by vascular perfusion. EC anionic sites were
      labelled with the probes cationic colloidal gold (CCG) and cationic ferritin
      (CF), using the pre- and post-embedding techniques, and examined by electron
      microscopy. The effects of enzyme digestion of ultrathin sections on subsequent
      CCG labelling were determined using a battery of enzymes in association with the
      post-embedding technique. CCG labelling was quantified following each enzyme
      treatment using image analysis software. The biotinylated lectin wheat germ
      agglutinin (WGA) with streptavidin gold was also used to localize specific
      monosaccharide residues. The luminal front of intraneural EC showed a uniform
      labelling with CCG and CF which was greater than on the abluminal surface.
      Extracellular matrix components and basal laminae were moderately labelled.
      Digestion of tissue sections with heparitinase and trypsin had no significant
      effect on subsequent CCG labelling. Proteinase K was less effective than papain
      but both produced a significant reduction. Neuraminidase almost completely
      eliminated labelling. CCG binding to the luminal plasma membrane of optic nerve
      EC can be significantly reduced with proteolytic and glycolytic enzymes. The
      results demonstrate that sialoglycoproteins principally constitute these luminal
      EC anionic sites. Biotinylated WGA-streptavidin gold, which detects both N
      acetylneuraminic (sialic) acid and N-acetylglucosamine, gave a similar pattern of
      labelling to CCG alone on the luminal versus abluminal EC fronts. These findings
      suggest that WGA is binding predominantly to N-acetylneuraminic acid residues
      since CCG would not label the neutral (uncharged) N-acetylglucosamine.

PMID- 8549681
TI  - Presence of beta-citryl-L-glutamic acid in the lens: its possible role in the
      differentiation of lens epithelial cells into fiber cells.
AB  - The beta-CG concentration in the chicken brain was high during embryonic
      development and decreased rapidly to a lower level close to hatching, while the
      concentration in the eyeball which was also high during the embryonic life
      retained a fairly high level after hatching. The distribution of beta-CG in the
      bovine eye was determined. About 95% of total beta-CG content in the whole eye
      was localized in the lens. However, the distribution of beta-CG in the eye varied
      depending on species. beta-CG was exclusively localized in the lens in the eyes
      of fish and mammals, but distributed in both lens and retina in frogs. The
      molecule was localized in the retina rather than the lens in the chicken eye,
      although the concentrations was extremely low compared to those in the mammalian,
      amphibian and fish eyes. It was found that beta-CG is present ubiquitously in the
      lens or retina in various species. The distribution of beta-CG in the bovine lens
      was determined in the three cortex regions and nucleus. beta-CG was present at
      the highest concentration in the equatorial cortex, at a moderate concentration
      in the posterior and anterior cortex, and at the lowest concentration in the
      nucleus. Similar distribution patterns were also found in the rabbit and rat
      lens. When embryonic chick lens epithelial cells were cultured in the presence of
      fetal calf serum, the cells elongated, differentiated into fiber cells and formed
      lentoid bodies. The cells of lentoid bodies were stained strongly by the anti
      beta-CG antibody, while cells around the structures were not. In addition, the
      beta-CG content in the lenses from the galactose cataractous rat decreased to
      about 20-30% of that in the normal lens. These findings suggest that beta-CG may
      play a role in the differentiation of epithelial cells into fiber cells.

PMID- 8549682
TI  - Effect of cross-linking on the chaperone-like function of alpha crystallin.
AB  - Alpha crystallin can function as a molecular chaperone in suppressing the heat
      induced aggregation of other crystallins and proteins. During cataractogenesis,
      alpha-crystallin becomes a water-insoluble, high-molecular-weight, cross-linked
      aggregate. To determine whether the chaperone activity of alpha crystallin is
      lost during this age-related modification, extracts were prepared by sonication
      of water-insoluble proteins isolated from aged bovine lenses and human cataract
      lenses. All the preparations were tested for chaperone-like activity using beta L
      crystallin as the target protein and the percentage of alpha-crystallin in water
      insoluble sonicated supernatant (WISS) was determined by slot blot immunoassay.
      The WISS from bovine as well as human lenses were still effective in protecting
      beta L-crystallin aggregation at 56 degrees C. The bovine cortical WISS with 50%
      immunoreactive alpha-crystallin showed 62% of the chaperone-like activity
      displayed by native alpha-crystallin. The WISS from bovine lens nucleus and human
      lenses with 17% and 5% immunoreactive alpha-crystallin showed 19% and 4%
      chaperone-like activity compared to native alpha-crystallin. Prior treatment of
      the WISS of both bovine and human lenses with dithiothreitol resulted in nearly
      50% increase in chaperone-like activity suggesting possible loss of chaperone
      like activity due to disulfide cross-links. To see if the chaperone-like activity
      of alpha-crystallin can be altered by non-disulfide cross-linking, native alpha
      crystallin isolated from bovine lenses was cross-linked with dimethylsuberimidate
      (DMS) and dimethyl 3,3'-dithiobispropionimidate (DTBP) and tested for chaperone
      like activity. The DMS cross-linked alpha-crystallin was effective in inhibiting
      the aggregation of beta L-crystallins at 56 degrees C, but required a two- to
      five-fold higher concentration than the native alpha-crystallin. alpha-Crystallin
      with higher degree of cross-linking showed lower chaperone-like activity. alpha
      Crystallin cross-linked with DTBP, a cleavable cross-linking agent, also showed a
      80% loss in chaperone-like activity. However, when the DTBP cross-linked alpha
      crystallin was treated with dithiothreitol to cleave the cross-links there was a
      50% recovery in the chaperone-like activity. These data suggest that the age
      related cross-linking, which restricts the molecular flexibility of alpha
      crystallin decreases its chaperone-like function.

PMID- 8549683
TI  - Beta B2-crystallin in the mammalian retina.
AB  - beta-crystallins are abundant lens proteins in most, if not all vertebrate
      species. We have previously reported the presence of low levels of beta
      crystallins in chick non-lens tissues, both ocular and extra-ocular, including
      the expression of beta B2-crystallin in the retina. Here we report that
      extralenticular beta-crystallin expression is also found in mammals. beta B2
      crystallin is expressed in mouse and cat neural and pigmented retinas and in cat
      iris. Although present at levels lower than those found in the lens, the
      appearance and accumulation of beta B2-crystallin in the neural retina coincides
      with the functional maturation of this tissue.

PMID- 8549684
TI  - Inhibition of experimental autoimmune uveoretinitis by mycophenolate mofetil, an
      inhibitor of purine metabolism.
AB  - Mycophenolate mofetil (MM), an inhibitor of purine metabolism, was found to
      effectively inhibit the development of experimental autoimmune uveoretinitis
      (EAU) induced by S-antigen (SAg) in Lewis rats. MM completely inhibited EAU
      development in the majority of rats when administered daily, on days 0-13, at a
      dose of 30 mg kg-1 day-1. The drug was less effective, however, when given on
      days 7-20: minimal disease inhibition was achieved with the drug at 30 mg kg-1
      day-1, although at 60 mg kg-1 day-1 the drug inhibited EAU development in most
      treated rats during the period of its administration. MM also completely
      inhibited in most treated rats the development of EAU adoptively transferred by
      SAg-sensitized lymphocytes, thus depicting its capacity to inhibit the efferent
      limb of the immune response. Treatment with MM also suppressed the cellular and
      humoral immune responses against SAg, with a good correlation being observed
      between the inhibition of these responses and suppression of EAU in the different
      groups of rats. MM is currently being examined for its immunosuppressive effects
      in humans and the data recorded here thus suggest this compound may be useful in
      treatment of immune-mediated uveitic conditions.

PMID- 8549685
TI  - Coordinated activation of corneal wound response genes in vivo as observed by in
      situ hybridization.
AB  - We used subtractive screening of a cDNA library prepared from corneoscleral rims
      after cauterizing rat corneas. We identified 76 clones whose corresponding mRNA
      increased during the wound healing process in an in vivo model of injury which
      damages the corneal epithelium, stroma, and endothelium. Of these clones, 31
      sequences encode known proteins. Another 45 clones are novel sequences based on
      comparison with the GenBank/EMBL databases. Changes in the level of expression of
      the novel genes, and a selected number of the known genes, were examined by in
      situ hybridization 22 and 72 hr after corneal injury. The majority produced a
      'wound pattern' of expression such that the mRNAs were highly induced in all cell
      types adjacent to the wound site at 22 hr post injury. This signal decreased in
      intensity with distance from the wound site. In a subset of corneoslceral rims
      examined by in situ hybridization, the mRNAs for these genes were also highly
      induced in the limbal epithelium, where the progenitor corneal epithelial stem
      cells reside. By 72 hr, when acute tissue damage had been repaired, the induced
      mRNA was only faintly present in the thickened epithelium. Our results provide a
      useful framework for further studies defining the pathophysiological roles of the
      known and novel proteins encoded by the isolated cDNA clones.

PMID- 8549686
TI  - Protein kinase C substrates in corneal epithelium during wound healing: the
      phosphorylation of growth associated protein-43 (GAP-43).
AB  - Protein kinase C (PKC) plays an important role in regulating cell growth. In the
      cornea, alpha-PKC activity increases during wound-healing. This activation of PKC
      will result in the increased phosphorylation of specific PKC substrates. In this
      study, several PKC substrates of relative low molecular weight were identified
      and characterized in cytosol and membrane preparations obtained from rabbit
      corneal epithelium before and during wound-healing. Corneal epithelium proteins
      were phosphorylated by endogenous PKC and by alpha-PKC isolated from rabbit
      brain, and then analysed using SDS-PAGE. In cytosol, PKC substrates with apparent
      molecular weights of 20, 25, 30, 35, 50 and 55 kDa were phosphorylated by PKC.
      The phosphorylation of the substrates increased 3 and 7 days after total de
      epithelialization, due to the increase in alpha-PKC activity after wounding.
      However, when brain alpha-PKC was used as the exogenous source of PKC, there was
      a protein concentration-related decrease in the phosphorylation of corneal
      epithelium substrate after injury. This decreased phosphorylation of PKC
      substrates was inhibited by okadaic acid, a specific phosphatase inhibitor. The
      results suggest that an activated protein phosphatase takes part in controling
      the phosphorylation of PKC substrates during wound-healing. In the membrane
      fraction, a 60 kDa protein was phosphorylated by alpha-, beta- and gamma-PKC
      isoenzymes and was identified by Western blot as growth associated protein-43
      (GAP-43), a protein kinase C substrate involved in axon regeneration. GAP-43
      concentration increased 3 and 7 days after wounding as did its phosphorylation by
      alpha-PKC. These findings suggest a role for the protein in the innervation
      process in corneal epithelium after injury.

PMID- 8549688
TI  - Histopathology of rabbit eyes with silicone-fluorosilicone copolymer oil as six
      months internal retinal tamponade.
AB  - Silicone-fluorosilicone copolymer oil has low viscosity (175-185 cSt) and is
      heavier than water (density, 1.16 g cm-3). Short term retinal tolerance (within 2
      months) of the silicone-fluorosilicone copolymer oil has been reported to be the
      same as that of currently used intraocular silicone oil. Ocular response of the
      purified silicone-fluorosilicone copolymer oil were examined clinically and
      histopathologically from 2.5 months to 6 months after vitreous cavity injection
      in rabbit phakic eyes, and compared the oil tolerance with that of purified
      silicone oil (0.97 g cm-3, 5000 cSt). The effects in anterior chamber also were
      examined within 4 weeks of the silicone-fluorosilicone copolymer oil injection in
      different rabbits. Silicone-fluorosilicone copolymer oil recovered from the
      vitreous cavity at 6 months was analysed for cholesterol and retinol content by
      high performance liquid chromatography. Because of its low viscosity, silicone
      fluorosilicone copolymer oil was easy to inject and remove from the vitreous
      cavity with a 20-G needle. After the vitreous injection, discrete droplet
      formation by the silicone-fluorosilicone copolymer oil occurred more easily than
      by silicone oil. Medullary ray detachment was seen in a silicone oil-, and some
      silicone-fluorosilicone copolymer oil-injected eyes at 4-6 months.
      Histopathologically, after 3-6 months disappearance of outer plexiform layer and
      disorganization of the photoreceptor layer of silicone oil-, and silicone
      fluorosilicone copolymer oil-injected eyes were seen in the superior and the
      inferior retina, respectively. Migration of the photoreceptor cell nuclei to the
      photoreceptor layer was found in the inferior retina of silicone-fluorosilicone
      copolymer oil-injected eyes at 5-6 months. Small droplets ingested by mononuclear
      cells were found in the vitreous cavity or preretina at 4-6 months in silicone
      fluorosilicone copolymer oil-injected eyes. After the anterior chamber injection,
      silicone-fluorosilicone copolymer oil induced endothelial cell damage in the area
      where the oil contacted continuously. Retinol and cholesterol were identified in
      silicone-fluorosilicone copolymer oil removed from the vitreous cavity. Silicone
      fluorosilicone copolymer oil may be useful as an intraoperative device in retinal
      detachment surgery and as a short term (up to about 2 months) retinal tamponade
      but we do not recommend it for long term retinal tamponade.

PMID- 8549687
TI  - Comparative efficacy of antiviral drugs on human ocular fibroblasts.
AB  - The effects of several antiviral drugs on fibroblast attachment and proliferation
      from human Tenon's capsule were investigated. These drugs included purine
      nucleoside analogs, vidarabine and acyclovir (ACV); pyrimidine nucleoside analog,
      AZT; and a synthetic cyclic primary amine, amantadine. Fibroblast attachment and
      proliferation inhibition were determined by Coulter counter, a colorimetric assay
      of the enzyme hexosaminidase, and a 3H-thymidine uptake assay. Amantadine and AZT
      inhibited fibroblast attachment at concentrations higher than 6.61 x 10(-4)M and
      3.73 x 10(-4) M, respectively. Amantadine and AZT had inhibitory effects on
      fibroblast proliferation as early as day 1, whereas vidarabine and ACV manifested
      their inhibitory effects after day three by Coulter counter and hexosaminidase
      assays. For amantadine, AZT, ACV and vidarabine, the 50% inhibitory dose (ID50)
      were 4.94 x 10(-5) M, 1.26 x 10(-5) M, 4.60 x 10(-4) M, and 1.52 x 10(-5) M at
      day 9, respectively, as measured by 3H-thymidine uptake assay. All four antiviral
      agents tested had inhibitory effects on human ocular fibroblast proliferation and
      their inhibitory potential decreased in the order of amantadine > or = vidarabine
      > AZT > or = ACV.

PMID- 8549689
TI  - Manipulating rat lens glucose metabolism with exogenous substrates.
AB  - Diabetic lens glucose metabolism in vivo can be altered by a number of exogenous
      substrates. We have chosen two, one a glucose epimer (mannose) and the other a
      glycolytic intermediate (pyruvate), to demonstrate the possibility of this
      approach. D(+)-Mannose is a D(+)-glucose epimer but in lenses incubated in 35.5
      mM mannose, no mannitol (the sorbitol equivalent) was detected, while both
      lactate production and 31P profile appeared normal. Mannose therefore is a good
      glucose substitute causing no polyol formation. Mannose metabolism in the rat
      lens in vivo was then examined. Diabetic rats fed mannose-enriched diet over a
      period of 14 days showed retardation of changes in 31P metabolites, specifically
      the levels of phosphorylcholine and glycerophosphorylcholine, suggesting a
      protective effect. Rat lenses incubated in 35.5 mM glucose in the presence of 5
      mM pyruvate (pyr) showed 50% lower sorbitol than without pyr. With 5 mM pyr in
      the drinking water, i.e. pretreatment in vivo during a 3-day diabetes induction
      period, the diabetic rat lens accumulated acetate and alanine when incubated in
      the presence of pyr. The decrease in sorbitol was most likely due to a lower
      glucose flux rather than an increased polyol dehydrogenase activity. Increasing
      glucose concentration from 5.5 to 35.5 mM or provision of exogenous pyr both
      caused an intermediate increase in O2 consumption in the normal lens; a maximal
      activity was reached with both 35.5 mM glucose and 5 mM pyruvate in the
      incubating medium. In the diabetic lens, O2 consumption could reach the
      intermediate but not the maximal level. Dietary pyr pre-treatment also prevented
      normal and diabetic lenses from maximal pyr-stimulated O2 consumption. The NMR
      and O2 consumption data together indicated activation of alanine dehydrogenase
      and saturation of Krebs cycle. It appears that dietary supplement of mannose can
      preserve 31P membrane metabolites in the diabetic lens. Mannose can be used in
      conjunction with hypoglycemic therapy for the management of diabetic cataract. In
      addition, pyruvate may be effective in enhancing lens energy metabolism and lower
      sorbitol production.

PMID- 8549690
TI  - Natural, high-mannose glycoproteins inhibit ROS binding and ingestion by RPE cell
      cultures.
AB  - Previous studies have suggested that a mannose receptor mediates the phagocytic
      uptake of effete rod outer segments by retinal pigment epithelial cells. In the
      present study, the effect of adding a soluble ligand for the mannose receptor,
      horseradish peroxidase, was examined. Cultured retinal pigment epithelial cells
      from Long Evans rats were preincubated with various concentrations of horseradish
      peroxidase for 20 min followed by a challenge of FITC-labeled bovine rod outer
      segments for 3 h. Both counts of total rod outer segments (bound and ingested)
      and ingested rod outer segments were determined. Rod outer segment uptake was
      reduced, in a concentration-dependent fashion, by an average of 60% of control
      values when horseradish peroxidase was added to retinal pigment epithelial
      cultures. Similarly, total rod outer segment values were reduced to 50% of
      controls in the presence of at least a 10 micrograms ml-1 horseradish peroxidase
      concentration. Horseradish peroxidase inhibition of retinal pigment epithelial
      phagocytic capacity was reversible. Other high mannose glycoproteins, such as
      invertase, beta-glucoronidase, and ovalbumin, were equally effective in
      preventing rod outer segment ingestion by retinal pigment epithelial cells. These
      data further support the hypothesis that a mannose receptor on the retinal
      pigment epithelial apical surface facilitates phagocytosis of rod outer segments.

PMID- 8549691
TI  - The human lacrimal gland synthesizes apolipoprotein D mRNA in addition to tear
      prealbumin mRNA, both species encoding members of the lipocalin superfamily.
AB  - Apolipoprotein D (apoD), a glycoprotein originally characterized as a component
      of the high density lipoprotein fraction of human plasma and known to be a member
      of the lipocalin protein superfamily, has been found in human tear fluid by
      Western blot analysis. Unlike serum it seems that in the tear fluid apoD exists
      mainly as a disulphide linked homodimer which is not associated with
      lecithin/cholesterol acyltransferase (LCAT) or apolipoprotein A-I (apo A-I). By
      reverse-transcription-PCR (RT-PCR) of mRNA extracted from a human lacrimal gland
      and use of specific primers we could demonstrate expression of the apoD gene in
      this tissue. The amplified cDNA was cloned and a subsequent sequence analysis
      confirmed the identity of apoD mRNA in the human lacrimal gland. These
      investigations indicate that the lacrimal gland is the site of synthesis of the
      tear fluid apoD. Although the physiological function of apoD is unknown, it has
      the ability to bind phospholipids, cholesterol and other small hydrophobic
      molecules. Therefore, this protein might interact with meibomian lipids present
      in human tear fluid and probably contribute to the surface spreading of these
      lipids or it may function as a clearance factor, protecting the cornea from
      harmful lipophilic molecules.

PMID- 8549693
TI  - Dose-dependent effects of intravitreal pirenzepine on deprivation myopia and lens
      induced refractive errors in chickens.

PMID- 8549692
TI  - Redistribution of fodrin in an in vitro wound healing model of the corneal
      epithelium.
AB  - We previously observed the redistribution of a membrane skeletal protein, fodrin,
      after wounding in the corneal epithelium in vivo. In this study, we made an in
      vitro wound healing model using cultured corneal epithelial cells to investigate
      the redistribution mechanism of fodrin in the corneal epithelial cells. The
      distributional change of fodrin from the plasmalemma to the cytoplasm was
      observed soon after wounding by indirect immunofluorescence microscopy and laser
      scanning confocal microscopy. A similar change was caused by treating intact
      cells with phorbol-12-myristate-13-acetate (PMA), but not with calcium ionophore,
      A23187. The redistribution occurred even in cells pretreated with 1,2-bis(O
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetomethyl ester (BAPTA-AM)
      before wounding. The redistribution caused by wounding or by PMA was inhibited by
      pretreating the cells with protein kinase C inhibitors, H-7 or calphostin C.
      Moreover, the reagents were found to slow down the migration of corneal
      epithelial cells after wounding. These results suggest that the redistribution of
      fodrin in the wounded corneal epithelium is caused through the activation of
      protein kinase C and might be related to the ensuing cell migration.

PMID- 8549694
TI  - Rapid destruction of skeletal muscle fibers by mycelial growth forms of Candida
      albicans.
AB  - The process of tissue invasion by the yeast Candida albicans after subcutaneous
      inoculation into the footpad of mice has been examined by light and electron
      microscopy. The blastospores germinated within 2 hr after injection. Hyphal and,
      to a lesser extent, pseudohyphal elements were observed penetrating into the
      adjacent striated muscle fibers and the endothelial cells of capillaries and
      destroying the collagen bundles of the interstitium. Electron microscopy showed
      evidence of structural tissue degradation associated with the mycelial elements,
      particularly at the apical tip. This was presumably due to fungal enzymatic
      activity. By 3 hr after infection, polymorphonuclear leucocytes had engulfed both
      the extracellular and intracellular mycelia, and often there was structural
      evidence of mycelial degradation. The results provide morphological evidence that
      initial tissue damage following subcutaneous infection is caused by the mycelial
      growth form.

PMID- 8549695
TI  - E-cadherin and OB-cadherin mRNA levels in normal human colon and colon carcinoma.
AB  - A polymerase chain reaction strategy was utilized to identify members of the
      cadherin family of cell adhesion molecules that are expressed in normal human
      colon and colon carcinoma. E-cadherin (an epithelial cadherin) and OB-cadherin (a
      mesenchymal cadherin) were found to be present in the colon specimens.
      Furthermore, a novel semiquantitative polymerase chain reaction (PCR) assay was
      developed for each of these two cadherins. These assays were used to determine
      the relative levels of E-cadherin and OB-cadherin in normal human colon and colon
      carcinoma specimens. E-cadherin levels were found to be reduced approximately
      twofold in the adenocarcinoma specimens in comparison to matched normal colon
      specimens. In contrast, OB-cadherin levels did not correlate with malignant
      transformation. We speculate that this novel PCR method will be widely applicable
      for assessing E-cadherin mRNA levels in carcinomas.

PMID- 8549696
TI  - The preventive effect of oral administration of type I interferon on collagen
      induced arthritis in rats.
AB  - We investigated the effect of oral administration of type I interferon (IFN) on
      an autoimmune disease collagen-induced arthritis (CIA) in rats that was induced
      by immunization with type II collagen (CII). The results showed that the oral
      administration of IFN before immunization with CII significantly suppressed the
      development of CIA. Delayed type hypersensitivity, in vitro proliferative
      responses of lymph node cells to CII, and IL-2 production were also inhibited by
      the fed cytokine. The serum from IFN-fed animals downregulated the development of
      CIA and proliferative responses to CII. In contrast, IFN given orally after the
      onset of CIA failed to affect the proliferation of T cells to CII as well as the
      progression of the disease. There was a decrease in the production of anti-CII
      antibody in rats fed IFN before, but not after, immunization with CII. Thus,
      orally administered IFN may have preventive, but not therapeutic, effects on
      autoimmune inflammatory joint diseases.

PMID- 8549697
TI  - Differential short-term transduction efficiency of adult versus newborn mouse
      tissues by adenoviral recombinants.
AB  - We demonstrated different transduction efficiency in several major organs of the
      immature (newborn) versus mature (adult) mice using adenoviral recombinants
      containing expression cassettes for either firefly luciferase or bacterial beta
      galactosidase reporter genes. The studied tissues included skeletal muscle,
      heart, brain, lung, kidney, and liver. The transduction efficiency in all
      tissues, especially skeletal muscle, was significantly less in adults than in
      newborns, with two exceptions. In the heart, transduction efficiency was the same
      in newborns and adults, while in brain, it was greater in the adult than in the
      newborn. The cited differences in transduction efficiencies between newborn and
      adult tissues applied approximately equally to both reporter genes. The alpha v
      integrin level showed the same trend as the transduction efficiency in all
      tissues, except the heart. Polymerase chain reaction showed a specific adenoviral
      product in proportion to the reporter gene expression in muscle, heart, and
      brain. The results of this study should be considered in designing gene therapy
      strategies in genetic diseases.

PMID- 8549698
TI  - Trifluopromazine late preventive effects on carbon tetrachloride-induced liver
      necrosis.
AB  - Trifluopromazine (TFPro) administration to rats (50 mg/kg, ip) 30 min before or 6
      or 10 hr after CCl4 treatment (1 ml/kg ip in olive oil) partially prevented
      necrogenic effects of this compound at 24 hr. TFPro has only minor effects on the
      covalent binding (CB) of CCl4-reactive metabolites to cellular constituents and
      even an enhancing action on CCl4-promoted lipid peroxidation (LP). Determination
      of TFPro levels in liver 1 and 3 hr after administration by gas
      chromatography/mass spectrometry showed its presence in that tissue at
      concentrations well above those needed for calmodulin (CaM) inhibitory effects of
      this drug. TFPro lowered body temperature in CCl4-treated animals during the 24
      hr observation period. Protective effects of TFPro at 6 or 10 hr, when most of
      the CB and all of the LP has already occurred, suggest but do not prove a role
      for CaM in late stages of CCl4-induced necrogenic effects. Decreases in the body
      temperature of CCl4-poisoned animals provoked by TFPro might also play a role in
      the preventive actions of this drug.

PMID- 8549699
TI  - Coexpression of a novel glomerular basement membrane matrix material in mesangial
      cell culture and glomerulosclerosis.
AB  - After in vivo administration of purified antibody against cultured mesangial cell
      (anti-MC IgG), glomerular basement membrane (GBM) was selectively bound. The
      glomerular bound anti-MC IgG exhibited a monospecificity for a 109-kDa antigen
      extracted from cultured mesangial cells and normal GBM. The antigen was not
      digestible by collagenase, heparitinase, or chondroitinase and was revealed by
      immunoelectron microscopy of a normal glomerular component to be predominantly
      distributed along the lamina rara externa of GBM and to be absent in mesangium.
      The ample expression of the antigen in puromycin aminonucleoside nephrosis
      implies that it represents a significant sclerotic material in
      glomerulonephritis. Abnormal production of GBM components by mesangial cells may
      play an important role in glomerulosclerosis.

PMID- 8549700
TI  - Antibody protection in aging: influence of idiotypic repertoire and antibody
      binding activity to a bacterial antigen.
AB  - Previous studies demonstrated that the anti-phosphorylcholine (PC) antibodies
      produced by aged BALB/c (18-22 months old) mice are structurally different and
      less protective against infection with Streptococcus pneumoniae than those
      produced by young (3-4 months old) syngeneic mice. However, PC antibody from aged
      animals had a different idiotypic repertoire and, at the same time, showed a
      diminished antibody binding activity to pneumococci compared to "young" antibody.
      To determine the cause of the reduced protective activity of the "aged" antibody,
      experiments of passive protection were performed using anti-PC monoclonal
      antibody (mAb) from either young and aged BALB/c or young syngeneic mice that
      were neonatally injected with an equimolar mixture of two monoclonal antibodies
      specific for two distinct idiotopes of the T15 idiotype (Id) family. At
      young/adult age, the mice neonatally injected with anti-Id antibody were still
      able to respond to PC, but the idiotypic repertoire was characterized by the
      absence of the dominant T15 idiotype. The two groups of mAb generated had a
      similar affinity to PC and binding activity to pneumococci but were totally
      diverse in regard to both their idiotypic repertoire and VH/VL gene utilization.
      Experiments of passive protection allowed us to determine the influence of the
      idiotypic repertoire and antibody binding activity to pneumococci on the reduced
      antibody protective efficiency in aging. Young recipients (BALB/c) were injected
      ip with a dose of anti-PC mAb from young, either T15Id+ or T15Id-, and aged
      donors (20 micrograms/recipient) and 2 hr later the groups of mice were
      challenged with 10(3) CFU of S. pneumoniae WU-2. Both groups of "young" antibody
      afforded a similar degree of protection, regardless of the idiotypic repertoire,
      always higher than that of PC antibody from aged mice. These experiments
      suggested that the decline of binding activity, and not the switch in the
      idiotypic repertoire, may be responsible for the reduced anti-pneumococcal
      activity of the anti-PC antibody on aging.

PMID- 8549701
TI  - To use or not to use the odds ratio in epidemiologic analyses?
AB  - This paper argues that the use of the odds ratio parameter in epidemiology needs
      to be considered with a view to the specific study design and the types of
      exposure and disease data at hand. Frequently, the odds ratio measure is being
      used instead of the risk ratio or the incidence-proportion ratio in cohort
      studies or as an estimate for the incidence-density ratio in case-referent
      studies. Therefore, the analyses of epidemiologic data have produced biased
      estimates and the presentation of results has been misleading. However, the odds
      ratio can be relinquished as an effect measure for these study designs; and, the
      application of the case-base sampling approach permits the incidence ratio and
      difference measures to be estimated without any untenable assumptions. For the
      Poisson regression, the odds ratio is not a parameter of interest; only the risk
      or rate ratio and difference are relevant. For the conditional logistic
      regression in matched case-referent studies, the odds ratio remains useful, but
      only when it is interpreted as an estimate of the incidence-density ratio. Thus
      the odds ratio should, in general, give way to the incidence ratio and difference
      as the measures of choice for exposure effect in epidemiology.

PMID- 8549702
TI  - Personality self-representations of patients with hand injury, and its
      relationship with work injury.
AB  - This study compared the personality self-representations of 288 hand injured
      patients with those of 959 young people (15-25 years old) randomly selected from
      the general population (noted GP), and with those of 336 unemployed people of all
      ages in professional training (U) in Lorraine (north-eastern France). The
      relationship between patients' personality self-representations and injury was
      also investigated. Personality self-representations included 14 questions: in
      your own opinion are you sociable?, at ease with others?, serious?, careful?,
      dynamic?, optimistic?, worried?, irritable?, clumsy?, solitary?, organised?,
      ambitious?, do you have a sense of responsibility?, and many plans? The patients
      had similar self-representations to GP except for the items non clumsy (odds
      ratio adjusted on age and sex OR = 2.40, p < 0.05) and optimistic (OR = 1.70, but
      0.05 < p < 0.10). The frequencies of non irritable, non clumsy and non solitary
      people were higher in patients than in the U group (OR about 2.40, p < 0.01). By
      contrast, the other items were more favourable for the U group except for the
      items sociable, organised and having many plans. Self-representation items were
      significantly related to some socio-demographic data. The work injured workmen
      having one or more previous work injuries during the last five years were more at
      ease with others than the other subjects. Among the work injured workmen who had
      had no previous work injury during this time, the people aged 29 or less (the
      highest risk age class) were more optimistic than the others (71% vs 49%, p <
      0.05); a difference was also found for the items at ease with others, careful,
      dynamic, and non worried, but it was not significant possibly due to the small
      number of subjects. The sum of these five items differed between the two age
      groups (3.29 +/- 1.49 vs 2.55 +/- 1.68, p < 0.05). These simple items would
      provide an interesting approach in terms of personality which could explain in
      part the excess of work injuries in young people, though the work requirement
      still seemed to be the highest risk factor.

PMID- 8549703
TI  - Serologic response to rickettsial antigens in patients with Astrakhan fever.
AB  - Astrakhan fever is a new spotted fever group (SFG) rickettsiosis. Sera of
      patients with Astrakhan fever have been examined by microimmunofluorescence and
      western immunoblotting to determine the serologic responses to the Astrakhan
      strain and to R. conorii M-1 strain and the Israelian isolate of SFG rickettsiae.
      The serologic response to specific rickettsial agent and to Israelian isolate has
      been found to be similar, but was different of that to R. conorii. Immunoglobulin
      G (IgG) and IgM antibodies were detected in most sera and were directed against
      the lipopolysaccharide. Only one of tested sera contained IgG antibodies which
      also recognized high molecular weight proteins.

PMID- 8549704
TI  - Antibodies to spotted fever group rickettsiae in dogs in Croatia.
AB  - The prevalence of IgG antibodies to spotted fever group rickettsiae was studied
      by the indirect immunofluorescent antibody assay in a sample of 194 canine sera
      from different parts of Croatia. Dogs (n = 141) from urban and suburban-semirural
      environs from the middle part of the eastern coast of Adriatic sea, and dogs (n =
      53) from Zagreb, the capital of Croatia located in the northern continental part
      of Croatia, were tested. The total of 88 (62.4%) dogs from southern coastal
      Croatia had antibodies to Rickettsia conorii, with a significantly higher
      prevalence (69.9%) in suburban-semirural areas. The prevalence rate of antibodies
      to Rickettsia conorii in canine sera from urban environment in the north of
      Croatia was 20.7%. The results show that the members of spotted fever group
      rickettsiae are present in both coastal and continental Croatia.

PMID- 8549705
TI  - Epidemiology of meningococcal infections in children in mid-southern part of
      Turkey.
AB  - 59 patients were treated for meningococcal infections in Cukurova University
      Faculty of Medicine, Division of Pediatric Infectious Diseases. 50.8% of patients
      were male, 33.9% were under two years of age and 61% were under five. 78% of
      patients were admitted to hospital in winter and spring time. Meningococcal
      meningitis (MM) was present in 39% of patients on admission, however,
      meningococcemia in 27.1% and meningococcemia and meningococcic meningitis
      (Meningococcemia + MM) in 33.9%. Fatality rate was 18.6% and no association was
      found between mortality and clinical type of disease (p > 0.05), but mortality
      ratio decreased with an increasing age (p < 0.01). No deaths occurred among the
      12 patients who received i.v. penicillin treatment shortly before admitting to
      hospital, on the other hand 11 of 47 patients (23.4%) without such a previous
      treatment died.

PMID- 8549706
TI  - An epidemic of hepatitis B virus infection among intravenous drug users in
      Iceland.
AB  - This study describes an outbreak of hepatitis B primarily among intravenous drug
      users in Iceland which has a population with a very low incidence of hepatitis B
      virus infection. The incidence of acute hepatitis B is generally low in the
      Nordic Countries, in the order of one to five cases per 100,000 people per year.
      Between 1989 and 1992 there was an outbreak of hepatitis B virus infection
      primarily among the intravenous drug user (IVDU) population in Iceland. At the
      Department of Medical Virology, University of Iceland there were 44 cases of
      acute hepatitis B identified during the peak year 1990, an incidence of 16.9
      cases of acute hepatitis B per 100,000 people. 63.6% of these were known to be
      IVDUs. The seroprevalence of the hepatitis B core antibody (anti-HBc) marker was
      assessed among 1100 randomly selected individuals. The average prevalence of this
      marker was 2.9% and rose from zero at the age of 15 and younger to 6.5% at the
      age of 65 and older. Among IVDUs attending a detoxification clinic in 1990 the
      prevalence of the anti-HBc was 32%. In contrast, those attending the same clinic,
      due to alcoholism only, did not have a significantly higher prevalence of anti
      HBc than the group used for comparison.

PMID- 8549707
TI  - Mortality, morbidity and drug consumption in a rural area (Spain).
AB  - A descriptive study was made of the health indicators in 5 rural municipalities
      of the province of Castellon (Spain), with a total of 1428 inhabitants. This
      population is characterized by its aging, 36.9% of all individuals being older
      than 65 years. A retrospective evaluation was made of the annual mortality rates
      between 1940 and 1990, and of morbidity and medications consumption for the
      period between June 1991 and May 1992. An increase in general mortality was
      observed during the study period, though the rates also diminished in relation to
      age groups, sex and cause of death. In addition, 59.45% of the study population
      made use of health-care services in the course of one year, an average of 2.59
      drugs being prescribed per inhabitant in that same period. Morbidity in
      decreasing order of importance was attributed to acute respiratory disease,
      osteomuscular disorders, hypertension, depression and gastric pathology.
      Medications for the common cold and coughing were the most frequently used drugs,
      along with pain-killers, cardioactive agents, psycholeptics and non-sterioidal
      anti-inflammatory drugs (NSAIDs). Aging causes the mortality variations recorded,
      despite the socio-sanitary improvements observed in the zone during the study
      period. Aging may also be related to the important use of healthcare services and
      of drugs noted in the study. The highest morbidity rates and drug consumption
      levels corresponded to chronic diseases that deteriorate patient quality of life
      without actually increasing mortality.

PMID- 8549709
TI  - AIDS: awareness and blood handling practices of health care workers in Lagos,
      Nigeria.
AB  - A questionnaire survey of 260 health care workers from 13 randomly selected
      health care facilities was undertaken. Their knowledge, attitude, belief and
      blood handling practices regarding HIV/AIDS were enquired about. Virtually all
      (99.0%) respondents had heard about AIDS but only 57.0% had seen an AIDS patient
      before. Although 83.0% knew that AIDS is caused by a virus, a high proportion
      still confuses mode of transmission with causative agent. Deficient knowledge was
      exhibited when asked about groups of people who were at a higher risk of
      contracting HIV and AIDS: Only 54.6% and 51.5% identified homosexuals and i.v.
      drug users as being at a higher risk. Almost all (97.0%) of our respondents
      claimed to have been more careful in their blood handling practices since the
      emergence of AIDS, 68.5% wore gloves for all procedures involving handling of
      blood and 28.5% sometimes although as many as 30.4%, 40.4% and 18.1% do not wear
      gloves for cleaning up blood stained materials, nursing procedures and taking
      obstetric delivery respectively. It was evident from their responses that not all
      the health workers knew the correct method for disposing of used bloodstained
      instruments and left-over blood samples and neither were they all adhering to the
      safety guidelines recommended for handling these materials. Education of all
      health care workers in Nigeria on the Universal Precautions Guidelines issued by
      the Centers for Disease Control (CDC) in 1987 regarding blood, body fluids and
      contaminated instruments' handling precautions is urgently recommended.

PMID- 8549708
TI  - The seroprevalence of ten zoonoses in two villages of Crete, Greece.
AB  - The seroprevalence and incidence of 10 zoonoses due to Rickettsia typhi, R.
      conorii, Coxiella burnetii, Burcella sp., Borrelia sp., Toxoplasma sp.,
      Leishmania sp., Entamoeba histolytica, Echinococcus granulosus and Fasciola
      hepatica were studied in an animal husbandry and a farming village in Crete,
      Greece. The serum conversion incidence of each infectious agent was determined by
      testing 2 blood samples, collected in 1985 and in 1987. The surveillance was
      conducted using detailed transparent maps of the 2 villages studied, on which
      epidemiological data were interrelated to the results obtained from the
      serological tests. Thus the importance and spread of each infection were
      visualized. C. burnetii, Toxoplasma sp., R. conorii, and E. granulosus, were the
      most common infectious agents encountered during this study.

PMID- 8549710
TI  - Risk factors for laryngeal cancer.
AB  - This case-control study comprised 100 histologically verified laryngeal cancer
      patients and 100 hospital controls matched with cases by sex, age and place of
      residence. The following variables were tested for their association with cancer
      of the larynx: marital status, educational level, hard liquor consumption,
      cigarette smoking, unfavorable working conditions, sudden and frequent
      temperature changes at work, cold housing, loud speech at work, frequent
      hoarseness, frequent and persistent cough, persistently swollen neck glands,
      tonsillectomy and laryngeal surgery. According to conditional logistic regression
      analysis, significant association with laryngeal cancer was found for
      unfavourable working conditions for more than 10 years (OR = 4.36; 95% CI = 1.92
      9.91), hard liquor consumption for more than 5 years (OR = 2.59; 95% CI = 1.14
      5.87), cigarette smoking for more than 10 years (OR = 7.29; 95% CI = 2.41-22.09),
      tonsillectomy (OR = 4.80; 95% CI = 1.61-14.30) and frequent and persistent cough
      prior to disease (OR = 8.17; 95% CI = 1.72-38.76).

PMID- 8549711
TI  - Primary liver cancer in a high-incidence area in north Italy: etiological
      hypotheses arising from routinely collected data.
AB  - The incidence rate for primary liver cancer (PLC) was investigated in the Health
      Unit of Brescia (about 325,000 inhabitants), North Italy, in the 5-year period
      1986-90, in order to ascertain whether there was a high risk for developing the
      disease in the area as suggested by mortality data. A total of 349 incident cases
      were observed (male: female ratio = 3.4: 1), of which 182 (52.1%) were diagnosed
      through histology. The cumulative risk was about 5% and 1% in males and females,
      respectively. The crude incidence rates were 34.5/100,000 in males and
      9.4/100,000 in females, and the age-standardized rates were the highest among all
      those observed in the 9 Italian areas covered by Cancer Registries. Although
      about half of the cases in males can be attributed to either chronic alcoholic
      disease or HBV infection or both, further research is needed to investigate the
      role of known risk factors for PLC in the Health Unit.

PMID- 8549712
TI  - Cancers of the female genital tract in Ragusa, Sicily.
AB  - A descriptive study of cancers of the female genital tract (cervix, endometrium,
      ovary, labia, vulva and vagina) in the province of Ragusa (Sicily) was carried
      out using incidence and mortality data of the Ragusa Cancer Registry, covering
      the years 1981-1987. Corpus uteri was the most frequent site of cancer, followed
      by cervix utery and ovary; the highest mortality rates were exhibited by ovary
      cancer, whose survival at five years was 18.1 percent. A comparison of incidence
      and mortality rates with those observed by Italian and European registries shows
      that while in Ragusa rates for cancers of all sites were lower, female genital
      tract cancers, particularly of the uterus, were more frequent in Ragusa than in
      other Italian and European areas. In contrast with what has been reported by
      cancer registries of most developed countries, incidence of cervix cancer in
      Ragusa has apparently not decreased between 1981 and 1987, while mortality has
      increased.

PMID- 8549713
TI  - Epidemiology of eclampsia.
AB  - The purpose of this study was to examine the risk of eclampsia in relation to
      several maternal characteristics and exposures, including demographic
      characteristics, reproductive history, and tobacco use during pregnancy. A case
      control study was conducted using data for all singleton births from the
      Washington State birth certificates for 1984-1990. In the check box feature
      employed by these certificates, eclampsia is listed under maternal conditions.
      Risk estimates, adjusted for various confounders, were calculated comparing
      eclampsia among exposed versus unexposed women. The risk of eclampsia was
      elevated in women without prenatal care, those with weight gain of more than
      thirty pounds during pregnancy, nulliparous women, and those with chronic
      hypertension. The association with tobacco smoking were inverse and dose related.
      Women's race, urban or rural place of residence, history of pre-term births, and
      anemia were not associated with eclampsia. Our data reaffirm the importance of
      prenatal care, and provide further evidence of an inverse relationship with
      prenatal smoking. As eclampsia and pre-eclampsia are important pregnancy
      complications, further research is needed to explore their possible causes.

PMID- 8549714
TI  - In vitro activity of commercially manufactured disinfectants against Pseudomonas
      aeruginosa.
AB  - The in vitro activity of 17 commercially manufactured disinfectants routinely
      used in a large teaching hospital was tested against 128 strains of Pseudomonas
      aeruginosa isolated from hospitalized patients and the hospital environment.
      Except for quaternary ammonium salts, all the disinfectants at dilutions higher
      or equalling those recommended by the manufacturer were adequate to suppress P.
      aeruginosa. Chlorhexidine-, povidone-iodine- and glutaraldehyde-based
      disinfectants at dilutions 4 to 8-fold lower than the normal use dilution had a
      marked bactericidal effect ( > 3 log10 reduction of viable cells) within a short
      time (10 to 120 min). Similar formulations produced by different manufacturers
      exhibited comparable activity against P. aeruginosa.

PMID- 8549715
TI  - Pityriasis rosea Gibert: detection of Legionella micdadei antibodies in patients.
AB  - Some epidemiological and clinical characteristics of Pityriasis rosea Gibert has
      led us to hypothesize that this disease may be the clinical manifestation of an
      infection caused by legionellas. We have thus tested the sera of 36 patients ill
      with Pityriasis rosea and 19 controls for Legionella pneumophila serogroup 1-6
      and Legionella micdadei antibodies. These, who had the same age and sex
      distribution as study patients, were receiving treatment for other diseases in
      the same ward. Also tested were 200 sera from the voluntary blood donors from the
      same region as study patients. Legionella micdadei antibodies were detected in 12
      (33.3%) Pityriasis rosea cases and in one (5.2%) control. They were significantly
      more common in Pityriasis rosea cases than in either controls or voluntary blood
      donor population. The findings to date encourage continued research into the
      causative relationship between the Legionella micddadei infection and the onset
      of Pityriasis rosea Gibert.

PMID- 8549716
TI  - Occurrence of different genospecies of Borrelia burgdorferi sensu lato in ixodid
      ticks of Valais, Switzerland.
AB  - A total of 825 adult ticks (727 Ixodes ricinus, 72 Dermacentor marginatus and 26
      Haemaphysalis punctata) was collected from vegetation in Valais (Switzerland) in
      1987 to 1992. They were examined for the presence of Borrelia burgdorferi sensu
      lato, the etiologic agent of Lyme borreliosis. B. burgdorferi sensu lato was
      detected by indirect immunofluorescence assay, dark field microscopy and/or
      culture in 221 out of 727 I. ricinus (30.4%) and none in the other two species.
      From these 221 infected ticks we obtained 50 isolates. Indirect
      immunofluorescence assay and culture were used for all ticks but dark field
      examination has also been performed and compared to the two above mentioned
      methods for 231 I. ricinus. Indirect immunofluorescence assay and culture were
      used for all ticks but dark field examination has also been performed and
      compared to the two above mentioned methods for 231 I. ricinus. Indirect
      immunofluorescence was found the most efficient method for the detection of
      Borrelia in ticks with 54 positive out of 231, followed by dark field examination
      with 35 positive and culture with 12 isolates. We found no site free of Borrelia
      where I. ricinus is present. The rate of infection varied from 9.7 to 47.5%, as
      detected by the addition of the three methods. Typing of the 50 isolates revealed
      also a nonhomogeneous distribution of the Borrelia species. Based on the
      electrophoretic mobility of the OspA and B and immunostaining with species
      specific monoclonal antibodies (H3TS for B. burgdorferi sensu stricto, D6 for B.
      garinii and J8.3 for B. afzelii) 4 groups could be observed. Half of the isolates
      (n = 26) were typed as B. burgdorferi sensu stricto, 19 as B. garinii, 3 as B.
      afzelii and 2 as group VS116. This forth group formed of two isolates from one
      location is genetically distinct from the 3 former species described in Europe so
      far. The Borreliae of this group are unreactive with any of the three monoclonal
      antibodies used.

PMID- 8549717
TI  - Prevalence of ticks infected with Francisella tularensis in natural foci of
      tularemia in western Slovakia.
AB  - The prevalence of ticks infected with F. tularensis was followed during a
      systematic surveillance in endemic area of tularemia in western Slovakia over the
      years 1984-93. Ticks were collected from vegetation in localities of Podunajske
      Biskupice, in the vicinity of the capital of Slovakia, Bratislava, near the river
      Danube. In total 6033 ticks, mostly adults of Dermacentor reticulatus and Ixodes
      ricinus (4994 and 1004, respectively) and 35 nymphs of Haemaphysalis concinna,
      were examined for the presence of F. tularensis. Out of 4542 starving ticks, 34
      F. tularensis strains were isolated predominantly from D. reticulatus (30), and
      to a smaller extent also from I. ricinus (3) and H. concinna (1). Natural
      infection with F. tularensis was further proved from 1491 adults of D.
      reticulatus fed on laboratory animals, rabbits and white mice, together in 27
      cases. From that, 21 times it was by positive isolation either from suspensions
      of partly or fully engorged ticks and their feaces, or from spleens of animals
      dead after the feeding of ticks. In addition, solely the development of
      antibodies against the agent was confirmed in 6 rabbit hosts. The presence of F.
      tularensis in all the above mentioned tick species and namely the relatively high
      and permanent infestation of D. reticulatus adults, ranging between 0.5-2% during
      the followed time period, demonstrated the maintenance of active natural focus of
      tularemia in the area under study. The present paper also emphasizes the
      epidemiologic consequence of various species of ticks in endemic foci of
      tularemia and the aspect of possible ways of transmission of the agent to humans.

PMID- 8549718
TI  - Prevalence of Legionella pneumophila serogroup 1 antibodies in blood donors.
AB  - The prevalence of anti-Legionella pneumophila serogroup 1 antibodies in 777 blood
      donors of the Turin area was determined by the indirect immunofluorescence assay
      (IFA) and by the microagglutination test (MA). Low titers (IFA of 1/16 and MA of
      1/8) were found in 0.3% of the subjects. A statistically significant difference
      was not observed by sex and by age for IFA titers, but was noted by sex for MA
      titers of > or = 1/4 (p < 0.05). The upper limit of normal titer was < 1/8 by IFA
      and < 1/4 by MA at 15% cutoff level and 1/8 by IFA and 1/4 by MA at 1% cutoff
      level. In conclusion, the prevalence of antibodies in the Turin area was very
      low; IFA titers of > or = 1/64 and MA titers of > 1/16 can be considered as
      presumptive of infection in a single serum specimen of a patient with pneumonia;
      no change in the epidemiology of the disease was observed in the recent years.

PMID- 8549719
TI  - Differentiation of strains from a food-borne outbreak of Salmonella enterica by
      phenotypic and genetic typing methods.
AB  - A combination of typing methods was used to identify the strains and the
      infection source in a food-borne outbreak of Salmonella enterica occurring in a
      summer camp and affecting 25 children. All isolates tested were found to be
      serovar Enteritidis, with an identical biotype API 20E and ribotype. However,
      they differed in their plasmid profiles and/or antibiograms, and were grouped
      into three strains. One strain was found in human stools, another in a hen's egg,
      and the third in both stools and another egg pointing to large Spanish omelettes
      to be the contaminated food source.

PMID- 8549720
TI  - Prevention of cardiovascular disease: from biomedical research to health policy.
AB  - Cardiovascular diseases (CVD) are the leading cause of premature death and
      disability in the developed world. Broad consensus exists on CVD preventability
      through reduction of their risk factors at both the individual and population
      level. The latter kind of intervention implies involvement of policy-making
      institutions, owing to the manifold implications (agriculture, industry,
      environment) of such programmes. They have to be developed through three phases
      in succession: observational studies; intervention trials; public health action
      programmes. The implementation of the latter can only result from merging of
      biomedicine and politics and must rest on sound scientific-ethical bases. Other
      important issues are cost effectiveness, resort to mass media, transfer to other
      communities, funding and institutionalization. As a practical example of
      development and implementation of a public health programme, the experience of
      the ATS-Sardegna Campaign is briefly described.

PMID- 8549721
TI  - Cadaver kidney transplantation: ethics and consent.
AB  - Organ transplantation began to develop soon after the Second World War. The
      constant progress made in organ transplantation has resulted in an increase in
      the number of operations carried out. The laws governing transplantation are
      often drawn up to deal with the de facto situation in a particular country. The
      study focuses on Guideline 1 adopted by 44th World Health Assembly (resolution
      WHA 44-25) concerning consent in cadaver kidney transplantation. The discussion
      of the question of consent is based on a comparative study of the laws regarding
      kidney transplantation in the countries of what is known as Greater Europe. The
      points of discussion presented are not offered with a view to advocating a system
      where soliciting the consent of the family would be considered as ethically
      necessary. Given the current legal constraints, the presumed consent procedure,
      with consultation of the family would appear to be more appropriate.

PMID- 8549722
TI  - Evaluation of non-radioactive temperature gradient SSCP analysis and of
      temperature gradient gel electrophoresis for the detection of HPV 6-variants in
      condylomata acuminata and Buschke-Loewenstein tumours.
AB  - A modified non-radioactive single strand conformation polymorphism analysis
      incorporating a temperature gradient (TG-SSCP) and temperature gradient gel
      electrophoresis (TGGE) were evaluated for the detection of human papillomavirus
      type 6 (HPV 6)-variants in 41 condylomata acuminata and 5 Buschke-Loewenstein
      tumours. TG-SSCP and TGGE analysed part of the transforming ORF E6 of HPV 6
      spanning nucleotides 10 to 495. TG-SSCP distinguished between 8 HPV 6-variants
      whereas TGGE demonstrated 6 different DNA-species. HPV 6-strains found in Buschke
      Loewenstein tumours did not vary in the analysed portion of the E6 ORF as
      compared to ordinary condylomata acuminata. TG-SSCP and TGGE further showed
      absence of double infection with different HPV 6-strains in the analysed samples.
      Our results demonstrated that both methods may be successfully used for the
      detection of different strains of microbiological agents, although TG-SSCP seemed
      to provide easier execution and to confer a higher degree of flexibility than
      TGGE.

PMID- 8549723
TI  - Pathogenic Nocardia isolated from clinical specimens including those of AIDS
      patients in Thailand.
AB  - Forty strains of nocardioform microorganisms were isolated as clinical specimens
      including several from AIDS patients in Thailand. Among them, 37 strains were
      found to belong to the genus Nocardia. Our identification studies revealed that
      most of the strains (25 strains) belong to the N. asteroides group, i.e., N.
      asteroides sensu stricto and N. farcinica. Three strains were identified as N.
      otitidiscaviarum and two strains N. brasiliensis. In addition, 7 strains of rare
      pathogenic N. transvalensis were also isolated.

PMID- 8549724
TI  - Completeness of AIDS reporting and quality of AIDS death certification in Tuscany
      (Italy): a linkage study between surveillance system of cases and death
      certificates.
AB  - In Italy, the AIDS cases defined according to the CDC criteria are reported to
      the National AIDS Registry (RAIDS, compulsory surveillance system). The aim of
      the present study is to evaluate the completeness of AIDS cases reported and the
      quality of AIDS death certification in an Italian Region (Tuscany, about
      3,500,000 inhabitants). The 737 AIDS cases reported to RAIDS as residents in
      Tuscany (1987-91) were cross-linked (key link: name and date of birth) with the
      data of the Mortality Registration system of the Region (RMR). For the residents
      in Tuscany decreased with a 279.1 death diagnosis (the code for AIDS deaths
      stated by the Italian Census Bureau) and not reported to RAIDS as AIDS cases, the
      clinical records were reviewed to check whether the diagnosis fitted the 1987-CDC
      diagnostic criteria. This study shows that there is a high completeness (97-98%)
      of the AIDS cases resident in Tuscany, reported to the RAIDS. The quality of
      RAIDS data is not as good with regard to life status assessment (23% of under
      reporting of death). In Tuscany, the death certification for AIDS (code 279.1 of
      ICD IX) has a sensitivity of 88% and a specificity around 100% in comparison to
      RAIDS. About 50% of 'false negatives' in death certification are due to causes of
      death presumably unrelated to HIV infection. The evaluation of the quality of
      AIDS surveillance and mortality data is important in the assessment of the impact
      for AIDS epidemic in a target population.

PMID- 8549725
TI  - Survival differences in Austrian patients with the acquired immunodeficiency
      syndrome.
AB  - We investigated the association of clinical and demographic factors on survival
      of the 901 AIDS cases diagnosed until 31 December 1992 and reported to the
      Austrian Health Authorities up to 20 January 1994. The overall estimated median
      survival of patients with AIDS increased substantially from 8 months in 1987 to
      16 months in 1988, although this increase was not significant by the log-rank
      test. However, the differences in hazard rates were larger at the beginning of
      the survival curve: between 1987 and 1988 the proportion surviving at 1 year
      increased from 41 to 62%, compared to an increase of the proportion surviving at
      2 years from 30 to 35% (Breslow test, p value 0.008). AIDS patients diagnosed
      between 1988 and 1992 (n = 755) were analyzed in more detail. Multivariate
      survival analysis revealed a shorter survival for those with residence in Eastern
      Austria, recipients of blood products, individuals with unknown transmission
      risk, those presenting with two AIDS indicator diseases and those with higher age
      at AIDS diagnosis. Candidal esophagitis as AIDS indicator disease was associated
      with longer survival. One hundred eighty-eight of the 755 AIDS patients (24.9%)
      died within the first 3 months after diagnosis of AIDS. We conclude that the
      survival time for AIDS patients has improved considerably after 1987, but
      survival is still very poor. Several factors have been shown to predict survival
      of patients with AIDS in Austria. Death within the first 3 months after the
      diagnosis of AIDS occurred at a relatively high frequency in Austrian AIDS
      patients. This may be caused by difficulties in the use of health care facilities
      or by the lack of awareness of HIV infection before diagnosis of AIDS either by
      patient or care provider.

PMID- 8549726
TI  - Human T-cell leukemia virus type II infection among high risk groups and its
      influence on HIV-1 disease progression.
AB  - The prevalence and the risk factors of the human T-cell leukemia virus type I/II
      (HTLV-I/II) infection were evaluated among 552 individuals at high risk for HIV
      1. HTLV infections showed a low (1.6%) prevalence, were restricted to intravenous
      drug addicts and were due to HTLV-II alone. Moreover, in order to weigh the
      influence of HTLV-II on the natural history of HIV-1 infection, the clinical
      outcome of HIV-1 disease was compared between subjects with and without HTLV-II
      coinfection. Our findings showed that HTLV-II does not adversely affect the
      outcome of HIV-1 infection. Infact, a slower disease progression has been
      recorded in some HTLV-II coinfected subjects.

PMID- 8549727
TI  - Seroconversion to HBV associated with seroconversion to HIV in a cohort of
      intravenous drug misusers in Turin, Italy.
AB  - Between March 1986 and March 1994, the seroconversion to HBV associated to the
      seroconversion to HIV was investigated in 120 HIV seroconverters drawn from 2368
      i.v. drug misusers screened for HIV, HBV and STDs. Among the 185 individuals
      susceptible to HIV and HBV at intake (41/120 HIV seroconverters and 144/364 HIV
      negative controls), HBV seroconversion was associated with the seroconversion to
      HIV (p = 0.006) and history of more than 3 sexual partners per year (p = 0.000).
      Only the history of more than 3 partners per year remained associated with the
      HBV seroconversion in the conditional regression. The associated seroconversion
      to HIV and HBV was linked to the short period of i.v. drug injections (p =
      0.032), history of more than 3 partners per year (p = 0.000) and more than 3 i.v.
      drug injections per day (p = 0.016). Compared to the seroconverters to HBV alone,
      the seroconverters to HBV and HIV were likely to have higher frequency of i.v.
      drug injection per day on univariate (p = 0.031) and multivariate analysis (p =
      0.024). The seroconverters to both the viruses differed from the seroconverters
      to HIV alone in the year of drug debut (p = 0.045), short period of i.v. drug use
      (p = 0.048) and high frequency of injection per day (p = 0.008). The multivariate
      analysis confirmed only the association with high frequency of injection per day
      (p = 0.033). Higher risk of HIV seroconversion from the debut of i.v. drug use
      was observed in the subjects with concurrent HBV seroconversion (Log-Rank test: p
      = 0.0008).

PMID- 8549729
TI  - Quantification of Coxiella burnetii by polymerase chain reaction (PCR) and a
      colorimetric microtiter plate hybridization assay (CMHA).
AB  - A colorimetric microtiter plate hybridization assay (CMHA) for the quantitative
      determination of Coxiella burnetii DNA after amplification by externally
      controlled polymerase chain reaction (PCR) is described. The quantification assay
      is based on an enzyme linked immunosorbent assay (ELISA) format. Cloned DNA,
      representing a sequence complementary to an internal part of the diagnostic
      amplicon, was noncovalently attached to the wells of a microtiter plate.
      Biotinylated PCR product was hybridized to the immobilized capture probe. Bound
      product was detected via streptavidin horse-radish peroxidase. The devised
      nonisotopic technique allows specific, rapid, and convenient quantification of C.
      burnetii DNA. Additionally, it is compatible with standard laboratory ELISA
      equipment, making this assay amenable to automation and permitting processing of
      large sample numbers.

PMID- 8549730
TI  - Sequencing and linkage analysis of a Coxiella burnetii 2.1 kb NotI fragment.
AB  - Most of the Coxiella burnetii isolates (72 of 80) available in our institute
      share a 2.1 kb NotI fragment. Sequence analysis revealed two incomplete open
      reading frames (ORF) for putative genes hemA and bcR coding for glutamyl-tRNA
      reductase and bicyclomycin resistance protein, respectively. Upon completing the
      ORF for the hemA gene by sequencing the adjacent NotI/EcoRI fragment a third ORF
      for the putative prfA gene was determined coding for release factor 1, an enzyme
      catalysing the last step in protein biosynthesis.

PMID- 8549728
TI  - Asthmatic risk factors and bronchial reactivity in non-diagnosed asthmatic
      adults.
AB  - Specific respiratory signs and symptoms are thought to occur prior to diagnoses
      of asthma as part of the natural history. These signs and symptoms include: high
      IgE, a history of wheezing symptoms, and/or excessive declines in lung function.
      The first two are thought to distinguish asthma from other airway obstructive
      diseases (AOD). To predict subsequent AOD, twelve years of follow-up (1972-84)
      data from the Tucson longitudinal epidemiological study of AOD in a community
      population were evaluated on 687 subjects aged 19-70 years on entry. To determine
      the likelihood that non-asthmatics that have these specific risk factors would
      have marked or intermediate bronchial reactivity to methacholine, an experimental
      study was performed. This was done in 1984-85 in a robust, efficient post-hoc
      stratified sample of male subjects ages 30-55 from the population followed from
      1972. They were subsequently followed through 1991. Persistent symptoms best
      predicted final pulmonary function and new diagnosed AOD in subjects in the
      population. Previously diagnosed AOD also predicted lower pulmonary function. The
      experimental results indicate that predisposition to reactivity appears likely
      without the presence of diagnosed asthma. Further, the experimental subjects with
      high risk had increased symptomatology and decreased lung function when tested at
      follow-up; not all of the reactivity was explained by these factors. An attempt
      to predict reactivity by physician evaluation and special questionnaire was not
      fruitful. In addition, wheeze per se often disappeared without later evidence of
      asthma (or AOD) diagnosis, questioning some international tendencies to label all
      wheeze as asthma. Thus, high IgE significantly predicted bronchial
      responsiveness, but high IgE and symptoms are neither necessary nor sufficient.
      Also, both preclinical and clinical asthma predict eventual low lung function.

PMID- 8549731
TI  - A unique pattern of apo(a) polymorphism in an isolated east Greenlandic Inuit
      (Eskimo) population.
AB  - Eskimos of the east coast of Greenland very rarely had contacts with Caucasians
      until late in the 19th century. Their genes are therefore likely to be similar to
      those in the original Eskimo gene pool. We have compared serum concentrations of
      Lp(a) and apo(a) phenotypes in 78 East Greenland Eskimos (EGE) with those in
      Eskimos from Western Greenland (WGE) (n = 100) and Caucasian Danes (n = 466).
      Lp(a) levels were higher in EGE (median: 11.9 mg/dl [95% CI: 9.1-16.4]) than in
      Danes (p < 0.01), (median: 6.3 mg/dl [95% CI: 5.5-7.3]) and WGE (p < 0.01),
      (median: 7.8 mg/dl [95% CI: 5.7-10.2]). Lp(a) concentrations above 30 mg/dl were
      (p < 0.05) more common in EGE (19%) than in WGE (9%) and similar (p = 0.89) to
      those in Danes (20%). Apo(a) molecules as small as S2 or smaller (S1, B and F)
      were present in 26% of Danes and in 3% of WGE but were absent in EGE (p < 0.01).
      In contrast, a large apo(a) variant (VS4) was present in 54% of EGE and 62% of
      WGE, whereas it was very rare in Danes (2%). Lp(a) concentrations were inversely
      associated with apo(a) size in EGE (p < 0.05), WGE (p < 0.01) and Danes (p <
      0.01), but EGE with S3 or S4 had significantly higher Lp(a) levels than Danes (p
      < 0.05) with the same phenotypes.

PMID- 8549732
TI  - Trends in hepatitis A virus infection with reference to the process of
      urbanization in the greater Madrid area (Spain).
AB  - Hepatitis A is an infection transmitted by the fecal-oral route. Endemicity
      within a specific country is directly related to sanitation and hygienic
      standards, while being inversely related to socioeconomic conditions. We studied
      how the process of urbanization witnessed in Madrid had influenced the
      transmission of hepatitis A infection. In the Madrid Autonomous Region, this
      process first began in the early sixties and was not brought to a close until the
      late seventies. Catalytic models were used to estimate the annual infection rate,
      lambda, on the basis of seroprevalence data stratified by age. A cohort effect
      related to a fall-off in infancy-related hepatitis A virus (HAV) is to be
      observed in the results for the last few years. The model permits four birth
      cohort-based groups to be differentiated by lambda: individuals born pre-1960,
      lambda = 0.082 (95% CI 0.095-0.070); those born in the early sixties, lambda =
      0.052 (95% CI 0.060-0.042); whose members were born in the late sixties, lambda =
      0.033 (95% CI 0.041-0.025); and those born in the late seventies, lambda = 0.017
      (95% CI 0.020-0.013). The first group includes those born before the urbanization
      process had started. The second and third groups coincide with the development
      stage of that process, hence exhibiting transitional rates. The fourth group
      reflects the process in its consolidation stage. This reduction in the
      transmission of infection has changed the manner of presentation, so that while
      isolated cases or small outbreaks tend to be more common nowadays, occasionally
      epidemics may evolve explosively. The average age at presentation has risen and
      the likelihood of symptomatic infection is higher.

PMID- 8549733
TI  - Sexual behavior of women with repeated episodes of vulvovaginal candidiasis.
AB  - One hundred and two women with a history of a median of six episodes of
      vulvovaginal candidiasis (VVC) and 204 age-matched controls participated in a
      structured in-depth interview on sexual behavior. Mean and median ages of the two
      groups were 26.7 and 26 years, respectively. Sexual characteristics, associated
      with VVC in crude analyses, were adjusted in multifactorial analyses for coital
      frequency, experience of casual sex, vaginal irritation, smoking, alcohol habits,
      and having a steady partner. In addition, education, as a measure of
      socioeconomic status, was added in the multifactorial analyses. VVC was not
      associated with multiple sexual partners or ever-experience of causal sex. Sexual
      variables that remained significant or were of borderline significance after
      adjustment were: age at first intercourse (p = 0.001), causal sex partners the
      previous month (odds ratio (OR) = 3.1), sex during menstruation (OR = 1.7),
      regular oral sex (OR = 2.4), experience of anal intercourse ever (OR = 2.4), oral
      intercourse the last month (OR = 3.1), and frequency of oral intercourse (p =
      0.02). Thus, the study indicates that certain sexual activities are associated
      with repeated episodes of VVC.

PMID- 8549734
TI  - Relevance of cholesterol screening in the United Arab Emirates. A preliminary
      study.
AB  - The incidence of ischemic heart disease is rising rapidly in many of the affluent
      Arab countries and it is known that hypercholesterolemia is a well established
      risk factor for coronary artery disease. This community-based study was
      undertaken to determine if elevated cholesterol is a problem in the United Arab
      Emirates in order to be able to evaluate the contribution of cholesterol as a
      risk factor for atherosclerosis in this environment. Volunteers were recruited at
      busy urban public sites. Data on age, sex, nationality, weight, blood pressure
      and smoking history were collected, and blood samples were taken for estimation
      of total cholesterol, hemoglobin and individual blood group. A raw data set was
      developed, with calculation of body mass index and subsequent statistical
      analysis carried out on a PC using the SPSS programme. In the 834 patients, there
      were 19 nationalities represented which were pooled into 7 groups (5 Arab and 2
      non Arab) according to their ethnic origins. The prevalence of
      hypercholesterolemia varied from 47.2-53% in the Arab Nationals and from 22.7 to
      44.5% in the non Arabs. The mean cholesterol levels of the Arab subgroups were
      similar and showed no difference, statistically. However, they were significantly
      higher than non Arabs, i.e. Indians (p < 0.001) and Iranians (p < 0.001).
      Similarly, within the Arab subgroups, the median cholesterol levels were no
      different but were higher than the non Arabs, i.e. Indians (p < 0.05) and
      Iranians (p < 0.001). No statistical difference was found in the distribution of
      cholesterol (high, borderline high or desirable levels) among the seven ethnic
      groups. Hypercholesterolemia appears to be a problem in most nationalities living
      within the UAE. Overall, it afflicts nearly 50% of the adult population. Although
      the ethnic Arab groupings have a wide range of socioeconomic attributes, the
      similarity of the distribution of cholesterol may point to an underlying innate
      genetic etiology or an environmental cause such as dietary overindulgence, or
      both. Urgent public health measures such as education, case finding and further
      screening programs are required.

PMID- 8549735
TI  - Viral contamination of environmental surfaces on a general paediatric ward and
      playroom in a major referral centre in Riyadh.
AB  - In order to determine the incidence of viral contamination of environmental
      surfaces in a hospital in Saudi Arabia. A 6-month prospective study was carried
      out on a general paediatric ward in which both enteric and respiratory viruses
      were screened. Weekly samples were taken between August 1993-February 1994. A
      total of 155 samples were taken in which 11 (7%) tested positive for rotavirus.
      No other viruses were detected. Internal and external temperatures were monitored
      and an increase in rotavirus incidence was noted with decrease in temperature.
      Rotavirus was detected on surfaces involving human activity (toilet handles,
      televisions, toys and vital signs chart). One patient had rotavirus on his hands
      but no staff were found to carry rotavirus. Further contamination of
      environmental surfaces (9%) was detected during an increased incidence of
      rotavirus infection. A proper programme of disinfection and handwashing is
      essential in order to eliminate this mode of transmission.

PMID- 8549736
TI  - Community control of hypertension at work-site: epidemiological data of the
      Agusta project.
AB  - In order to set up a program of community control of hypertension at the work
      site, 8811 employees belonging to 12 factories of the same company (Agusta SpA,
      Italy) were screened. Seven hundred and seventy-two subjects (8%) were found to
      be hypertensive; 48% of them were hypercholesterolemic, 44% were smokers, 5%
      presented with hyperglycemia and 4% had left ventricular hypertrophy. Multiple
      regression analysis showed a significant correlation between hypertension and
      age, hypercholesterolemia, body mass index, occupational exposure to noise
      exceeding 80 dB and, below the age of 40 years, the type of job. Seven hundred
      and twenty-nine hypertensives were assigned to pharmacological treatment. This
      group of patients will be followed up for 3 years.

PMID- 8549737
TI  - Canine seroprevalence of Rickettsia conorii infection (Mediterranean spotted
      fever) in Castilla y Leon (northwest Spain).
AB  - A seroepidemiological study was conducted in 308 dogs to determine the presence
      of antibodies to Rickettsia conorii, using an indirect immunofluorescence assay
      (IFA). Seven of the provinces of the Castilla y Leon region (Burgos, Leon,
      Palencia, Salamanca, Soria, Valladolid, and Zamora) were covered by the study. Of
      the 308 dogs analysed, 72 (23.4%) showed significant titers by IFA (1/40 or
      higher). Seroprevalences were significantly different between provinces of origin
      of the animals. These were below 30% in almost all the provinces studied, except
      for Salamanca province, where the percentage of seropositive dogs was much
      greater (93.3%). Potential risk factors (presence of ticks on the animals, age,
      sex, use, habitat, and season) relating to the presence of Mediterranean spotted
      fever, or Boutonneuse fever, were evaluated. Animals used for guard or pastor
      activities and those living in rural areas (these factors are closely linked),
      together with those suffering from tick infestation, had significantly higher
      seroprevalence than the remainder. The frequency of seropositive dogs increased
      during the summer months, and these coincide with the period of greatest activity
      by the vector. Sex and age variables were not identified as risk factors.

PMID- 8549738
TI  - A birth weight for gestational age standard based on data in the Swedish Medical
      Birth Registry, 1985-1989.
AB  - Birth weight curves according to gestational length are presented based on data
      from more than 480,000 singleton births, registered in the Medical Birth Registry
      and with gestational age based on ultrasound examinations in the majority of
      cases. Curves were constructed from the most common weights in each week (modes)
      for each sex and standard deviations were estimated under the assumption of a
      fixed coefficient of variation, the size of which was estimated from 40 weeks
      infants. This methodology makes it possible to construct graphs for specific
      subgroups of infants: such graphs for boys and girls for primiparous and
      multiparous women are given in the paper.

PMID- 8549739
TI  - The catalytic cycle of P-glycoprotein.
AB  - P-glycoprotein is a plasma-membrane glycoprotein which confers multidrug
      resistance on cells and displays ATP-driven drug-pumping in vitro. It contains
      two nucleotide-binding domains, and its structure places it in the 'ABC
      transporter' family. We review recent evidence that both nucleotide-sites bind
      and hydrolyse Mg-ATP. The two catalytic sites interact strongly. A minimal scheme
      for the MgATP hydrolysis reaction is presented. An alternating catalytic sites
      scheme is proposed, in which drug transport is coupled to relaxation of a high
      energy catalytic site conformation generated by the hydrolysis step. Other ABC
      transporters may show similar catalytic features.

PMID- 8549740
TI  - Amplification and expression of recombinant genes in serum-independent Chinese
      hamster ovary cells.
AB  - CHO SSF3 cells grow as a suspension culture in unmodified commercial medium with
      only low-molecular weight ingredients. Continuous serum-free culture unexpectedly
      induced expression of a low dihydrofolate reductase activity in the originally
      dhfr- CHO cells. Nevertheless, it was possible with methotrexate to induce
      amplification of a gene coding for the hybrid plasminogen activator K2tu-PA
      cotransfected with a dhfr gene. Expression of K2tu-PA expression was
      proportionally increased to that of dhfr, which was measured with fluorescent
      methotrexate. Because no serum proteases were present, secreted K2tu-PA was not
      converted to the enzymatically active form, but was exclusively recovered in
      proenzyme form.

PMID- 8549741
TI  - Protein phosphatase 1 interacts with p53BP2, a protein which binds to the tumour
      suppressor p53.
AB  - The p53 binding protein, termed p53BP2, was identified as a protein interacting
      with protein phosphatase 1 (PP1) in the yeast two hybrid system. The interaction
      was confirmed by co-immunoprecipitation of p53BP2 with epitope-tagged PP1 in
      vitro. The p53BP2-PP1 complex was stable to NaCl at concentrations which
      dissociate the p53-p53BP2 complex, and the binding of PP1 and p53 to p53BP2 was
      mutually exclusive. The region required for interaction with PP1 was shown to be
      contained within amino acids 297-431 of p53BP2, which includes two ankyrin
      repeats. The phosphorylase phosphatase activity of PP1 was inhibited by p53BP2 at
      nanomolar concentrations. These results suggest that PP1 may be involved in
      dephosphorylation and regulation of p53 through interaction with p53BP2.

PMID- 8549742
TI  - Evidence for A+(anti)-G(syn) mismatched base-pairing in d-GGTAAGCGTACC.
AB  - Two-dimensional NMR spectroscopy has been used to study the structure and
      hydrogen bonding scheme of A:G mismatched base pairing in d-GGTAAGCGTACC at pH
      5.8. Under the conditions of our study, the molecule forms a B-DNA helix, with
      the mismatched bases in the A+ anti)-G(syn) conformation. The adenosine exists in
      the protonated form. The NOESY spectrum in 90% H2O + 10% 2H2O has been used to
      assign all observable imino and amino protons including those involved in the
      A+(anti)-G(syn) base pair. Both the proton donors in the A:G mismatched inter
      base hydrogen bonding are situated on adenosine.

PMID- 8549743
TI  - Competitive inhibition of the 5-lipoxygenase-catalysed linoleate oxidation by
      arachidonic and 5-hydroperoxy-eicosatetraenoic acids.
AB  - Linoleic and arachidonic acids are competing substrates for 5-lipoxygenase from
      barley. When these two substrates are added simultaneously, arachidonic acid acts
      as a competitive inhibitor of linoleic acid oxidation with Ki of 20 microM, the
      same value as the Michaelis constant for arachidonate oxygenation by this enzyme
      (22 +/- 3 microM). Linoleic acid hydroperoxide accumulated in the reaction
      mixture does not inhibit the enzymatic process, while arachidonic acid
      hydroperoxy product (5-hydroperoxy-6,8,11,14-eicosatetraenoic acid) inhibits it
      with very low Ki equal to 0.5 microM.

PMID- 8549744
TI  - Oxidized low-density lipoprotein induces the production of superoxide by
      neutrophils.
AB  - Exposure of guinea pig peritoneal neutrophils to ox-LDL led to the production of
      superoxide, which was measured by the formation of superoxide-dependent
      chemiluminescence. The cells exposed to unoxidized LDL, e.g. native LDL, acetyl
      LDL, and self-aggregates of LDL showed no production of superoxide. The
      superoxide production was correlated with the levels of oxidative modification of
      LDL and reached a maximum between 10 and 30 min during incubation, but
      preincubating the cells with cytochalasin B decreased the superoxide production.
      These findings indicate that neutrophils rapidly take up ox-LDL by phagocytosis
      and generate superoxide which may cause superoxide-mediated lipid peroxidation in
      vivo.

PMID- 8549745
TI  - A new translational elongation factor for selenocysteyl-tRNA in eucaryotes.
AB  - In eucaryotes, selenocysteine (SeCys) was found in some selenoproteins, but SeCys
      tRNA was not recognized by EF-1 alpha. A different translational elongation
      factor for SeCys-tRNA must therefore supply SeCys-tRNA to the machinery of
      selenoprotein translation. I found this factor in bovine liver extracts with a
      UGA-programmed ribosome binding assay. The activity of binding of [75Se]SeCys
      tRNA to the UGA-programmed ribosomes was eluted in fractions 57-65 using a CM
      Sephadex C-25 column, and separated from EF-1 alpha (the activity of binding of
      [14C]Phe-tRNA to the UUU-programmed ribosomes) in fractions 25-37. EF-1 alpha in
      fraction 25 could discriminate (UUU)10 for [14C]Phe-tRNA. A factor in fraction 57
      could discriminate (UGA)10 for [75Se]SeCys-tRNA. The elution pattern of activity
      of binding of [75Se]SeCys-tRNA to the UGA-programmed ribosomes was almost
      identical to that of activity of protecting [75Se]SeCys-tRNA against alkaline
      hydrolysis (SePF activity) [FEBS Lett. 347 (1994) 137-142]. These two activities
      might depend on the same factor. The activity of binding of [75Se]SeCys-tRNA to
      the UGA-programmed ribosomes directly indicates that a factor in fraction 57 is a
      new translational elongation factor for SeCys-tRNA in eucaryotes.

PMID- 8549746
TI  - Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein
      syndrome type I.
AB  - Carbohydrate-deficient glycoprotein (CDG) syndromes are genetic multisystemic
      disorders characterized by defective N-glycosylation of serum and cellular
      proteins. The activity of phosphomannomutase was markedly deficient (< or = 10%
      of the control activity) in fibroblasts, liver and/or leucocytes of 6 patients
      with CDG syndrome type I. Other enzymes involved in the conversion of glucose to
      mannose 1-phosphate, as well as phosphoglucomutase, had normal activities.
      Phosphomannomutase activity was normal in fibroblasts of 2 patients with CDG
      syndrome type II. Since this enzyme provides the mannose 1-phosphate required for
      the initial steps of protein glycosylation, it is concluded that
      phosphomannomutase deficiency, which is first reported here for higher organisms,
      is a cause, and most likely the major one, of CDG syndrome type I.

PMID- 8549747
TI  - Different localization of spermidine/spermine N1-acetyltransferase and ornithine
      decarboxylase transcripts in the rat kidney.
AB  - In situ hybridization histochemistry of transverse sections from male rat kidney
      showed that the mRNA of the regulatory enzyme of polyamine degradation,
      spermidine/spermine N1-acetyltransferase, has a spotty distribution in the
      cortex, is low and diffused in the outer stripe and high and diffused in the
      inner stripe of the outer medulla. At the cellular level, this mRNA is solely
      expressed by the epithelium of the distal straight and convoluted nephron
      tubules. Since biosynthetic ornithine decarboxylase mRNA is solely found in the
      proximal straight tubules, it is proposed that polyamine biosynthesis and
      degradation occur at separate sites along the nephron.

PMID- 8549748
TI  - Study of heme Fe(III) ligated by OH- in cytochrome b-559 and its low temperature
      photochemistry in intact chloroplasts.
AB  - EPR properties of Cyt b-559 have been investigated in intact chloroplasts that
      are functionally competent in O2 evolution and in CO2 fixation. After chemical
      oxidation of Cyt b-559 by 10 mM 2,3-dicyano, 4,5-dichloro-p-benzoquinone (DDQ)
      the major part of Cyt b-559 is found to be present in the high spin Fe(III) form.
      Only a small fraction of low spin heme Fe(III) (less than 5%) was formed by
      chemical or light-induced oxidation. This fraction increased during aging of
      intact chloroplasts. A comparison with the EPR signal of Fe(III) in myoglobin
      (Mb) reveals that the structure of the high spin signal in intact chloroplasts is
      indicative for the presence of an axial OH- ligand at the heme Fe(III). This type
      of ligation comprised a considerable part (approximately 40%) of the total Cyt b
      559 content. Removal of the Mn-cluster caused a change of the EPR parameters of
      OH- ligation. When in intact chloroplasts the heme Fe is chemically oxidized to
      Fe(III) ligated by OH-, this OH- ligation disappeared after a subsequent
      illumination at 80K by red light. Upon illumination at 140K this disappearance
      was accompanied by the formation of a high spin Fe(III) that is not ligated by OH
      . These results are discussed in terms of removal of OH- from Fe(III) caused by
      structural changes or photooxidation at a complex of Cyt b-559 that could
      possibly also comprise the Mn-cluster. This photooxidation is assumed to be
      accompanied by the formation of a bound OH. radical. The possibility is discussed
      that this process is related to photosynthetic water oxidation.

PMID- 8549749
TI  - Cooperative phenomena in the photocycle of D96N mutant bacteriorhodopsin.
AB  - The M intermediate decay in the photocycle of D96N mutant bacteriorhodopsin does
      not depend on the light intensity of the exciting flash. Cooperative phenomena in
      the photocycle are revealed after addition of azide causing acceleration of the M
      decay and making it kinetically well separated from the N decay. Increase in the
      light intensity induces slight deceleration of the M decay and significant
      acceleration of the N decay. The data obtained directly confirm our recent model
      [Komrakov and Kaulen (1995) Biophys. Chem. 56, 113-119], according to which
      appearance of the Mslow intermediate in the photocycle of the wild type bR at
      high light intensity is due to destabilization of the N intermediate leading to
      the acceleration of the N-->M and N-->bR reactions.

PMID- 8549750
TI  - Squid photoreceptor phospholipase C is stimulated by membrane Gq alpha but not by
      soluble Gq alpha.
AB  - Phospholipase C (PLC) was purified from squid retina. Soluble Gq alpha, membrane
      Gq alpha and G beta gamma were isolated from GTP gamma S-treated and light
      illuminated photoreceptor membranes. The membrane Gq alpha stimulated
      phosphatidyl inositol-phospholipase C (PI-PLC) activity in a dose-dependent
      manner. Soluble Gq alpha and membrane G beta gamma showed no stimulating effects
      on PLC. GTP gamma S-binding was found exclusively in membrane fraction, with very
      little present in the KCl-soluble fraction which contained soluble Gq alpha.
      These results indicate that light-activated rhodopsin activates PLC through
      membrane-bound Gq alpha and suggest that the rhodopsin/Gq/PLC cascade might be
      the pathway of phototransduction in squid photoreceptors.

PMID- 8549751
TI  - Cloning and functional expression of the cDNA encoding a novel ATP-sensitive
      potassium channel subunit expressed in pancreatic beta-cells, brain, heart and
      skeletal muscle.
AB  - A cDNA clone encoding an inwardly-rectifying potassium channel subunit (Kir6.2)
      was isolated from an insulinoma cDNA library. The mRNA is strongly expressed in
      brain, skeletal muscle, cardiac muscle and in insulinoma cells, weakly expressed
      in lung and kidney and not detectable in spleen, liver or testis. Heterologous
      expression of Kir6.2 in HEK293 cells was only observed when the cDNA was
      cotransfected with that of the sulphonylurea receptor (SUR). Whole-cell
      Kir6.2/SUR currents were K(+)-selective, time-independent and showed weak inward
      rectification. They were blocked by external barium (5 mM), tolbutamide (Kd = 4.5
      microM) or quinine (20 microM) and by 5 mM intracellular ATP. The single-channel
      conductance was 73 pS. Single-channel activity was voltage-independent and was
      blocked by 1 mM intracellular ATP or 0.5 mM tolbutamide. We conclude that the
      Kir6.2/SUR channel complex comprises the ATP-sensitive K-channel.

PMID- 8549752
TI  - Spectroscopic identification of the heme axial ligation of cytochrome b558 in the
      NADPH oxidase of porcine neutrophils.
AB  - The combination of electron paramagnetic resonance (EPR), near-infrared magnetic
      circular dichroism (NIR-MCD) and resonance Raman (RR) spectroscopies at cryogenic
      temperatures has been used to identify the axial heme ligation of the low spin
      cytochrome b558 component of NADPH oxidase from porcine blood neutrophils. The
      EPR and NIR-MCD results indicate the presence of two distinct forms in frozen
      solution; one with a low field g-value at 3.23 and porphyrin(pi)-to-Fe(III)
      charge transfer maximum at 1660 nm and the other a low field g-value at 3.00 and
      porphyrin(pi)-to-Fe(III) charge transfer maximum at 1510 nm. On the basis of
      these properties and the RR studies, both are attributed to forms of cytochrome
      b558 with bis-histidine axial ligation. The origin of the observed heterogeneity,
      the location and identity of the specific histidines involved in ligating the
      heme, and the role of the heme prosthetic group in O2- production are discussed
      in light of these results.

PMID- 8549753
TI  - Chloroplast pentose-5-phosphate 3-epimerase from potato: cloning, cDNA sequence,
      and tissue-specific enzyme accumulation.
AB  - A cDNA clone encoding the chloroplast enzyme pentose-5-phosphate 3-epimerase (EC
      5.1.3.1) in potato (Solanum tuberosum) was isolated and sequenced. The deduced
      sequence of 235 amino acids is similar to protein sequences of bacterial
      epimerases. Northern blot analysis showed the highest level of epimerase mRNA
      expression in potato leaves, whereas it was low in roots, tubers, and stems.
      Epimerase protein is mulated only in plant tissues possessing chloroplasts, i.e.
      in land to a lesser extent in stem. In contrast, transketolase, a sequential
      enzyme of epimerase in the reductive and oxidative pentose phosphate cycle, is
      accumulated in all plant tissues.

PMID- 8549754
TI  - Glucose- and insulin-induced phosphorylation of the insulin receptor and its
      primary substrates IRS-1 and IRS-2 in rat pancreatic islets.
AB  - The presence of tyrosine-phosphorylated proteins was studied in cultured rat
      pancreatic islets. Immunoblotting performed with total extracts of islets
      cultured in the presence of 1.8 or 5.6 mM glucose revealed at least three
      distinct tyrosine-phosphorylated bands (25 kDa, 95 kDa and 165-185 kDa). After 12
      h incubation in medium containing 1.8 mM glucose, a pulse exposition to 11 or 22
      mM glucose or to 10(-7) M insulin led to a substantial increase in the
      phosphorylation of all three bands, with no appearance of novel bands.
      Immunoprecipitation with specific antibodies demonstrated that the signal
      detected at 95 kDa corresponds to the beta subunit of the insulin receptor (IR)
      while the band at 165-185 kDa corresponds to the early substrates of the insulin
      receptor, IRS-1 and IRS-2. Immunoprecipitation with IRS-1 or IRS-2 antisera
      detected their association with the lipid metabolizing enzyme
      phosphatidylinositol 3-kinase (PI 3-kinase). Thus, this is the first
      demonstration that elements involved in the insulin-signalling pathway of
      traditional target tissues are also present in pancreatic islets and are
      potentially involved in auto- and paracrine-signalling in this organ.

PMID- 8549755
TI  - Long-term potentiation requires activation of calcium-independent phospholipase
      A2.
AB  - The predominant phospholipase activity present in rat hippocampus is a calcium
      independent phospholipase A2 (302.9 +/- 19.8 pmol/mg.min for calcium-independent
      phospholipase A2 activity vs. 14.6 +/- 1.0 pmol/mg.min for calcium-dependent
      phospholipase A2 activity). This calcium-independent phospholipase A2 is
      exquisitely sensitive to inhibition by the mechanism-based inhibitor, (E)-6
      (bromomethylene)-tetrahydro-3-(1-naphthalenyl)-2H-pyran -2-one (BEL). Moreover,
      treatment of hippocampal slices with BEL prior to tetanic stimulation prevents
      the induction of LTP (40.8 +/- 5.6% increase in excitatory post-synaptic
      potential (EPSP) slope for control slices (n = 6) vs. 5.8 +/- 8.5% increase in
      EPSP slope for BEL-treated slices (n = 8)). Importantly, LTP can be induced
      following mechanism-based inhibition of phospholipase A2 by providing the end
      product of the phospholipase A2 reaction, arachidonic acid, during the
      application of tetanic stimulation. Furthermore, the induction of LTP after
      treatment with BEL is dependent on the stereoelectronic configuration of the
      fatty acid provided since eicosa-5,8,11-trienoic acid, but not eicosa-8,11,14
      trienoic acid, rescues LTP after BEL treatment (37.6 +/- 16.1% increase in EPSP
      slope for eicosa-5,8,11-trienoic acid vs. -3.7 +/- 5.2% increase in EPSP slope
      for eicosa-8,11,14-trienoic acid). Collectively, these results provide the first
      demonstration of the essential role of calcium-independent phospholipase A2 in
      synaptic plasticity.

PMID- 8549756
TI  - Conformational analysis of potent and very selective delta opioid dipeptide
      antagonists.
AB  - The delta selectivity and antagonism of peptides containing L-tetrahydro-3
      isoquinoline carboxylic acid (Tic) in second position can be attributed mainly to
      the Tyr-Tic unit. These properties can be further enhanced by substituting Tyr1
      with 2,6-dimethyl-L-tyrosyl (Dmt). Dmt-Tic-NH2, Dmt-Tic-OH, Dmt-Tic-Ala-NH2 and
      Dmt-Tic-Ala-OH are all more active and/or selective than the corresponding [Tyr1]
      parent peptides. In fact the selectivities of Dmt-Tic-OH and Dmt-Tic-Ala-OH are
      the highest ever recorded for opioid molecules. 1H NMR spectra in a DMSO/water
      mixture at 278 K reveal the presence of two similar conformers, characterised by
      a cis or trans Dmt-Tic bond, in all four peptides. A detailed conformational
      analysis in solution of Dmt-Tic-NH2 shows that these conformers have a shape very
      similar to that of the bioactive conformation of Tyr-Tic-NH2 and to that of
      naltrindole.

PMID- 8549757
TI  - Mutagenesis analysis of the membrane-proximal ligand binding site of the TGF-beta
      receptor type III extracellular domain.
AB  - There are two TGF-beta binding subdomains in the extracellular domain of receptor
      type III (proximal and distal in relation to the transmembrane domain). Here we
      present an extension of our analysis of the proximal binding site of receptor
      type III. Due to the original deletion mutagenesis strategy, our proximal binding
      site contained 19 amino acids from the N-terminal part of the receptor. By
      deleting these, we demonstrated that they did not contribute to the binding
      ability of the proximal binding site. We also produced a soluble, secreted form
      of the proximal binding site and demonstrated that it was able to bind TGF-beta.
      Finally, we analyzed the role of the three asparagine residues (580, 591, 595)
      that are located in the region of the receptor that is necessary for expression
      of a functional proximal binding site, and found that mutation of these residues
      individually to alanine did not affect ligand binding.

PMID- 8549758
TI  - Molecular cloning of the defense factor in the albumen gland of the sea hare
      Aplysia kurodai.
AB  - Aplysianin-A, an antibacterial glycoprotein in the albumen gland of the sea hare
      Aplysia kurodai, inhibited the growth of both Gram-positive and Gram-negative
      bacteria. Aplysianin-A cDNA clones were isolated from an albumen gland cDNA
      library. Sequence analysis reveals that aplysianin-A is produced as a precursor
      protein of 556 amino acid residues with a signal peptide of 19 amino acid
      residues and contains 6 potential N-glycosylation sites. Aplysianin-A mRNA was
      expressed tissue-specifically in the albumen gland. Homology search reveals that
      aplysianin-A has a 50% overall amino acid sequence homology to achacin, an
      antibacterial glycoprotein of the giant African snail Achatina fulica.

PMID- 8549759
TI  - Water-mediated conformational transitions in nicotinic receptor M2 helix bundles:
      a molecular dynamics study.
AB  - The ion channel of the nicotinic acetylcholine receptor is a water-filled pore
      formed by five M2 helix segments, one from each subunit. Molecular dynamics
      simulations on bundles of five M2 alpha 7 helices surrounding a central column of
      water and with caps of water molecules at either end of the pore have been used
      to explore the effects of intrapore water on helix packing. Interactions of water
      molecules with the N-terminal polar sidechains lead to a conformational
      transition from right- to left-handed supercoils during these stimulations. These
      studies reveal that the pore formed by the bundle of M2 helices is flexible. A
      structural role is proposed for water molecules in determining the geometry of
      bundles of isolated pore-forming helices.

PMID- 8549760
TI  - Molecular and functional characterization of a rat brain Kv beta 3 potassium
      channel subunit.
AB  - A novel potassium channel beta-subunit (Kv beta 3) was cloned from rat brain
      being the third member of a Kv beta subunit gene family. It is a protein of 403
      amino acid residues with a 68% amino acid sequence homology to Kv beta 1.1. Kv
      beta 3 is primarily expressed in rat brain having a distribution distinct to
      those of Kv beta 1.1 and Kv beta 2. This subunit also has a long N-terminal
      structure and induces inactivation in N-terminal deleted Kv1.4 but not in other
      members of the Kv1 channel family. Similarly to Kv beta 1.1, the Kv beta 3
      induced inactivation is regulated by the intracellular redox potential.

PMID- 8549761
TI  - Pb2+ reduces the current from NMDA receptors expressed in Xenopus oocytes.
AB  - We compared the effects of Pb2+ on four types of NMDA receptors expressed in
      Xenopus oocytes. Pb2+ reduced the currents evoked by glutamate and glycine. The
      Ki values of the receptors, epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 3/zeta 1
      and epsilon 4/zeta 1, were 39, 34, 54 and 42 microM, respectively, and their Hill
      coefficients were 0.53, 4.6, 0.52 and 0.37, respectively. The epsilon 2/zeta 1
      receptor that was inhibited in the presence of over 30 microM Pb2+ was not
      recovered to the control level after a Pb2+ washout for over 30 min, suggesting
      that epsilon 2/zeta 1 is responsible for the chronic Pb2+ intoxication in the
      nervous system.

PMID- 8549762
TI  - Wortmannin inhibits the activation of MAP kinase following vasopressin V1
      receptor stimulation.
AB  - Treatment of rat 3Y1 fibroblasts with vasopressin (AVP) results in a transient
      activation of MAP kinase as potent as with EGF and serum. An antagonist of
      vasopressin receptor V1, but not an antagonist of V2, inhibited the AVP-induced
      activation of MAP kinases, indicating that AVP activates MAP kinases through V1
      receptor. Prolonged TPA treatment of cells resulted in partial MAP kinase
      activation, indicating the presence of PKC-independent pathway. The pathway was
      inhibited by wortmannin, an inhibitor of PI3-kinase. The results suggest that
      wortmannin-sensitive molecules such as PI3-kinase, are involved in the V1
      receptor-mediated activation of the MAP kinase pathway independent of TPA
      sensitive PKC.

PMID- 8549763
TI  - Identification of multiple PEPC isogenes in leaves of the facultative
      Crassulacean acid metabolism (CAM) plant Kalanchoe blossfeldiana Poelln. cv. Tom
      Thumb.
AB  - In the facultative Crassulacean Acid Metabolism (CAM) plant Kulanchoe
      blossfeldiana cv. Tom Thumb, CAM can be induced by short-day treatment or water
      deficiency stress. From young leaves of well-watered and water-stressed
      individuals of this plant, cDNA clones coding for a partial sequence of the key
      enzyme of CAM, phosphoenolpyruvate carboxylase, were isolated after transcription
      of mRNA. cDNA polymorphism was established by enzyme restriction profiles and
      sequencing data. Four PEPC isogenes could be shown to exist in K. blossfeldiana
      forming two gene pairs, with 95%-98% homology inside and only 75% between the
      pairs. One cDNA sequence pair having a length of 1113 bp and an open reading
      frame of 371 AA was identified as PEPC isoform specific for the C3 state, whereas
      the pair having a length of 1116 bp and an open reading frame of 372 AA could be
      attributed to the CAM state. These results were confirmed by Southern Blot
      hybridization.

PMID- 8549764
TI  - Molecular cloning of mouse epiregulin, a novel epidermal growth factor-related
      protein, expressed in the early stage of development.
AB  - A cDNA clone encoding a novel epidermal growth factor (EGF)-related growth
      regulator, epiregulin, was isolated from a cDNA library prepared from a mouse
      fibroblast-derived tumor cell line, NIH3T3/clone T7. The predicted amino acid
      sequence revealed that the purified epiregulin peptide of 46-amino acids was
      synthesized as an internal segment of a 162-amino acid putative transmembrane
      precursor. The structural organization was similar to that of TGF-alpha precursor
      among the members of the EGF family. Although epiregulin transcript was not
      detected in several adult normal tissues by Northern blot analysis, approximately
      4.8-kb transcript was present in 7-day-old mouse embryo and then diminished to
      very low or undetectable levels. Our results suggest that epiregulin may play an
      important role in the regulation of epithelial cell growth during early
      development.

PMID- 8549765
TI  - 2,8-Diazido-ATP--a short-length bifunctional photoaffinity label for
      photoaffinity cross-linking of a stable F1 in ATP synthase (from thermophilic
      bacteria PS3).
AB  - To demonstrate the direct interfacial position of nucleotide binding sites
      between subunits of proteins we have synthesized the bifunctional photoaffinity
      label 2,8-diazidoadenosine 5'-triphosphate (2,8-DiN3ATP). UV irradiation of the
      F1-ATPase (TF1) from the thermophilic bacterium PS3 in the presence of 2,8
      DiN3ATP results in a nucleotide-dependent inactivation of the enzyme and in a
      nucleotide-dependent formation of alpha-beta crosslinks. The results confirm an
      interfacial localization of all the nucleotide binding sites on TF1.

PMID- 8549766
TI  - Modulation of Tax and PKA-mediated expression of HTLV-I promoter via cAMP
      response element binding and modulator proteins CREB and CREM.
AB  - Nuclear proteins of the human peripheral blood T lymphocytes that bind to the
      CREs located within three 21-bp repeat enhancers of the HTLV-I promoter belong to
      the CREB/CREM family of bZIP transcription factors. It has been shown previously
      that Tax enhances transactivation of these CREs by direct interactions with the
      bZIP domain of the transcription factors to stabilize DNA-binding. We show that
      CREB and CREM bind all three CRE sequences of the HTLV-I promoter which are
      important determinants in Tax-elicited transactivation as well as PKA-mediated
      activation of the HTLV-I promoter. Tax and PKA activate transcription from a HTLV
      I-LTR CAT reporter plasmid transfected to NIH 3T3 cells, and CREM attenuates the
      activation. In the context of a GAL4 CREB fusion protein in which the DNA-binding
      bZIP domain of CREB is replaced by GAL4 binding domain, a single amino acid
      substitution of serine-133, phosphorylated by PKA and critical for the
      transactivation function of CREB, attenuates both Tax and PKA-mediated
      transcriptional responses. These observations suggest that Tax enhances CREB
      mediated transactivation of the HTLV-I promoter by a mechanism apart from, and/or
      in addition to, the reported stabilization of DNA-binding by interaction with the
      bZIP domain of CREB.

PMID- 8549767
TI  - Orientation of purple membrane in combined electric and magnetic fields.
AB  - The orientation of purple membrane in gels for photoelectric measurements is
      relatively poor, when they are prepared with the standard technique of applying a
      DC electric field and rapid polymerization. We have improved it by adding a high
      magnetic field (17.5 T) and increasing the viscosity of the membrane suspension.
      This process has resulted so far in a 3-fold increase of the photoelectric
      signals obtained. The magnetic susceptibility of purple membrane was determined.

PMID- 8549768
TI  - 5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the
      AMP-activated protein kinase. Studies using bacterially expressed human protein
      phosphatase-2C alpha and native bovine protein phosphatase-2AC.
AB  - Human protein phosphatase-2C alpha (PP2C alpha) was purified to homogeneity after
      expression in Escherichia coli. AMP inhibited the dephosphorylation of AMP
      activated protein kinase (AMPK), but not phosphocasein, by PP2C alpha. The
      concentration dependence and the effects of other nucleotides (ATP and formycin A
      5'-monophosphate) suggest that AMP acts by binding to the same site which causes
      direct allosteric activation of AMPK. A similar, although less pronounced, effect
      was observed with another protein phosphatase (PP2AC). We have now shown that
      AMPK activates the AMPK cascade by four mechanisms, which should make the system
      exquisitely sensitive to changes in AMP concentration.

PMID- 8549769
TI  - G alpha-16 complements the signal transduction cascade of chemotactic receptors
      for complement factor C5a (C5a-R) and N-formylated peptides (fMLF-R) in Xenopus
      laevis oocytes: G alpha-16 couples to chemotactic receptors in Xenopus oocytes.
AB  - The human leukocyte chemoattractant receptors for complement factor C5a (C5a-R)
      and N-formylated peptides (fMLF-R) are important members of the superfamily of G
      protein coupled receptors (GPCR). Uniquely among the GPCR, these two receptors
      cannot be expressed in a functionally active form in the oocytes of the frog
      Xenopus laevis, but require substitution of total RNA of the myelomonocytic U-937
      or HL-60 cell lines, respectively. Recently, it was reported that the C5a-R may
      couple to the alpha subunit of G-16. We have tested this G-protein for its
      ability to complement the signal transduction cascade of the C5a-R and fMLF-R in
      Xenopus oocytes. Injection of cRNA for the C5a-R in combination with G alpha-16
      led to expression of a functional C5a-R as measured by ligand-induced whole cell
      current. In contrast to a previous report, the fMLF-R exhibited some residual
      functional activity when transiently expressed in Xenopus oocytes the extent of
      which could, however, substantially be increased by coexpression of G alpha-16.
      Thus, G alpha-16 complements the signal transduction cascade of both receptors in
      Xenopus laevis oocytes and is most likely the complementing factor present in the
      U-937 and HL-60 cell lines.

PMID- 8549770
TI  - Human REG family genes are tandemly ordered in a 95-kilobase region of chromosome
      2p12.
AB  - Reg, first isolated from a rat regenerating islet cDNA library, is expressed in
      regenerating islet beta-cells. Recently, it has been revealed that Reg and Reg
      related genes constitute a multigene family, the Reg family. In human, the four
      REG family genes, i.e., REG 1 alpha, REG 1 beta, REG-related sequence (RS) and
      HIP/PAP, have so far been isolated. In this study, we analyzed YAC clones
      containing the four genes and performed two-color FISH to determine the map order
      of the genes. The human REG family genes are tandemly ordered in the 95-kbp DNA
      region of chromosome 2p12 as follows: 2cen-HIP/PAP-RS-REG I alpha-REG I beta
      ptel.

PMID- 8549771
TI  - Heterologous complementation of peroxisome function in yeast: the Saccharomyces
      cerevisiae PAS3 gene restores peroxisome biogenesis in a Hansenula polymorpha
      per9 disruption mutant.
AB  - PER genes are essential for the biogenesis of peroxisomes in the yeast Hansenula
      polymorpha. Here we describe the functional complementation of a H. polymorpha
      per9 disruption strain (delta per9) by a heterologous gene. The Saccharomyces
      cerevisiae Pas3p, a homologue of per9p, restored peroxisome biogenesis and
      peroxisomal protein import in the delta per9 mutant, allowing it to grow again on
      methanol as sole carbon and energy source. This result shows that heterologous
      complementation of peroxisome function in yeast is indeed feasible and
      furthermore suggests that H. polymorpha delta per9 may be the candidate of choice
      to attempt the isolation of Per9p homologues from higher eukaryotes by functional
      complementation.

PMID- 8549772
TI  - Glucagon stimulates phosphorylation of different peptides in isolated periportal
      and perivenous hepatocytes.
AB  - The perivenous and periportal zones of the liver acinus differ in enzyme
      complements and capacities for gluconeogenesis, glycolysis and other metabolic
      processes. The biochemical factors governing this metabolic zonation are still
      poorly understood. Glucagon-mediated protein phosphorylation is an important
      factor in the regulation of hepatic metabolism. Here we show, by comparing the
      32P-labelling pattern of isolated periportal and perivenous hepatocytes, that
      glucagon promotes the phosphorylation of zone-specific peptides as well as three
      common peptides (glycogen phosphorylase, glycogen synthase and pyruvate kinase)
      in the two cell types. We propose that the zone-specific phosphorylation of
      peptides is an important factor governing the shortterm zonation of metabolic
      processes in the liver.

PMID- 8549773
TI  - Cyclic 3'-5'-adenosine monophosphate binds to annexin I and regulates calcium
      dependent membrane aggregation and ion channel activity.
AB  - The annexin (Anx) gene family comprises a set of calcium-dependent membrane
      binding proteins, which have been implicated in a wide variety of cellular
      processes including membrane fusion and calcium channel activity. We report here
      that cAMP activates Ca(2+)-dependent aggregation of both phosphatidylserine (PS)
      liposomes and bovine chromaffin granules driven by [des 1-12]annexin I
      (lipocortin I, Anx1). The mechanism of cAMP action involves an increase in AnxI
      dependent cooperativity on the rate of such a reaction without affecting the
      corresponding k1/2 values. Cyclic AMP causes the values of the Hill coefficient
      (nH) for AnxI to change from 3 to 6 in both PS liposomes and chromaffin granules.
      By contrast, ATP inhibits the rate of aggregation activity without affecting the
      cooperativity or the extent of aggregation process. We were also able to
      photolabel Anx1 specifically with an 8-azido analogue of cAMP by a calcium
      independent process. Such a process is saturable, yielding a Kd = 0.8 microM by
      Scatchard analysis. Specific displacement occurs in the presence of cAMP and ATP.
      Finally, we found that cAMP alters the conductance of calcium channels formed by
      AnxI in planar lipid bilayers. We interpret these data to indicate that AnxI
      binds both calcium and cAMP independently, and that both actions have functional
      consequences. This is the first report of a nucleotide binding function for a
      member of the annexin gene family.

PMID- 8549774
TI  - Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic
      yeast Pichia pastoris: pharmacological characterization and localization.
AB  - The methylotrophic yeast Pichia pastoris was tested for heterologous expression
      of the mouse 5-HT5A receptor. Three different expression plasmids were
      constructed where the cDNA of the receptor was cloned under the transcriptional
      control of the highly inducible promoter of the P. pastoris alcohol oxidase 1
      (AOX1) gen. The expression plasmids differed with respect to the signal sequences
      used for N-terminal fusion. In two cases the coding region was additionally fused
      to the c-myc tag to permit immunological detection of the receptor. Expression of
      functional receptor after transformation of strain GS115 was detected by
      radioligand binding using [3H]LSD. The construct with the best expression levels
      in strain GS115 was used for transformation of the protease deficient strain
      SMD1163. Here, the expression level was 2-8 times higher. Whole cells as well as
      crude membrane preparations of recombinant clones showed saturable binding of
      [3H]LSD with a Kd of approximately 1.9 nM. Receptor concentrations of
      approximately 22 pmol/mg membrane protein revealed the potential of the P.
      pastoris expression system for high level expression of membrane proteins. The
      pharmacological properties were comparable to those reported for the receptor
      expressed in mammalian systems.

PMID- 8549775
TI  - Evidence that the Saccharomyces cerevisiae CIF1 (GGS1/TPS1) gene modulates heat
      shock response positively.
AB  - The CIF1 gene (also called GGS1/TPS1) encodes a protein of the trehalose synthase
      complex that affects trehalose accumulation and general glucose sensing by
      Saccharomyces cerevisiae cells. There is considerable debate as to whether CIF1
      dependent trehalose accumulation is a determinant in heat shock-acquired
      thermotolerance. Thermosensitivity of cif1 mutants could alternatively, or also,
      be related to gene expression-signalling defects in such strains. Because many
      signal-dependent factors are involved in stress protection and repair in yeast,
      we have compared the expression of various stress response and heat shock genes
      in 'isogenic' CIF1 and cif1 strains growing exponentially in galactose medium.
      Transcription of CTT1, CIF1, HSP26, HSP82, HSP104, SSA4 and UB14 was notably
      lower in the cif1 mutant following heat shock. Moreover, a single copy of
      chromosomally integrated HSP104-lacZ fusion gave up to 5.5-fold more heat shock
      induction in the CIF1 strain compared to the cif1 mutant. We conclude that
      reduced heat shock-acquired thermotolerance in cif1-deletion mutants growing
      exponentially on galactose is more likely to result from a general reduction in
      expression of stress response and heat shock genes, than simply or solely through
      deficiency of trehalose accumulation. The possible role of CIF1 in modulating
      stress response is discussed.

PMID- 8549776
TI  - Induction of inducible nitric oxide synthase expression by neopterin in vascular
      smooth muscle cells.
AB  - The pteridine compounds neopterin and 7,8-dihydroneopterin serve as valuable
      indicators for the stimulation of the cellular immune system. Whether they
      exhibit distinct biochemical functions in the immunological process is at present
      under discussion. We show that neopterin, but not 7,8-dihydroneopterin, is a
      stimulus for iNOS gene expression in rat vascular smooth muscle cells in vitro.
      At a concentration of 20 microM, neopterin leads to an iNOS mRNA expression of
      2.5 amol iNOS cDNA/micrograms total RNA. When cells were coincubated with 20
      microM neopterin and 5 micrograms/ml lipopolysaccharide derived from Escherichia
      coli, at least an additive effect on iNOS mRNA expression could be detected (iNOS
      cDNA concentration was 5.0 amol/micrograms total RNA). We speculate that
      neopterin enhances the macrophage-induced extracellular toxicity. This might be
      of relevance in situations associated with excessive release of cytokines,
      neopterin, and nitric oxide, as observed in septic shock.

PMID- 8549777
TI  - VIP17/MAL, a proteolipid in apical transport vesicles.
AB  - VIP17 is a proteolipid enriched in the CHAPS-insoluble complexes from MDCK cells,
      and a candidate component of the molecular machinery responsible for the sorting
      and targeting of proteins to the apical surface. Cloning and sequencing of the
      cDNA encoding the protein revealed that it is the canine homolog of the human and
      rat MAL proteins. Analysis by immunofluorescence microscopy of epitope-tagged
      VIP17/MAL expressed transiently in BHK cells and stably in MDCK cells revealed a
      perinuclear, vesicular, and plasmalemmal staining. In MDCK cells the distribution
      was mainly in vesicular structures in the apical cytoplasm. These and other
      results suggest that VIP17/MAL is an important component in vesicular trafficking
      cycling between the Golgi complex and the apical plasma membrane.

PMID- 8549778
TI  - Characterization of proteins phosphorylated by the cAMP-dependent protein kinase
      of bovine heart mitochondria.
AB  - Characterization of two mitochondrial proteins of M(r) 42 and 18 kDa,
      respectively, phosphorylated by the cAMP-dependent protein kinase of bovine heart
      mitochondria (mtPKA), is presented. A 42 kDa protein is found to be loosely
      associated to complexes I, III and IV of the respiratory chain and complex V (ATP
      synthase) in the inner mitochondrial membrane. An 18 kDa protein is associated to
      complex I in the inner membrane and in a purified preparation of this complex
      where it can be phosphorylated by the isolated catalytic subunit of PKA.

PMID- 8549779
TI  - A new family of lipolytic plant enzymes with members in rice, arabidopsis and
      maize.
AB  - We have noted a striking similarity between the sequences of proteins in a novel
      family of lipases we recently reported [Upton, C. and Buckley, J. T. (1995)
      Trends Biol. Sci. 20, 178-9] and more than 120 sequences from the database of
      Expressed Sequence Tags (dbEST) which correspond to at least 30 unique genes from
      arabidopsis, rice and maize. A cDNA (Arab-1) corresponding to one of these
      sequences was isolated, sequenced and translated. There was significant
      similarity to sequences in the new lipase family over the entire open reading
      frame of Arab-1 and when expressed in E. coli, the gene product was lipolytic.
      Arab-1 and genes for some of the other plant proteins appear to be differentially
      expressed. They may play a role in the regulation of lipid metabolism during
      plant development.

PMID- 8549780
TI  - Differential effects of molecular chaperones on refolding of homologous proteins.
AB  - Three homologous aspartate aminotransferases with virtually identical spatial
      structures and pairwise amino acid sequence identities of > 40% differ markedly
      with respect to the yield of renaturation upon dilution from 6 M guanidine
      hydrochloride (mitochondrial << cytosolic < Escherichia coli). The enzymes also
      respond differently to molecular chaperones. GroEL/GroES, the Hsp60 homolog of E.
      coli, increased considerably the yield of renaturation of mitochondrial aspartate
      aminotransferase and to a lesser extent that of its cytosolic counterpart, but
      not that of the E. coli enzyme. DnaK/DnaJ/GrpE, the Hsp70 system of E. coli, also
      increased the yield of renaturation of mitochondrial aspartate aminotransferase.
      Apparently, specific features in the amino acid sequence or the folding pathway
      which are independent of the final secondary and tertiary structure determine the
      interactions of the folding proteins with the chaperone systems.

PMID- 8549781
TI  - Genes encoding the beta 1 subunit of voltage-dependent Na+ channel in rat, mouse
      and human contain conserved introns.
AB  - We provide evidence in this study that the 86-bp insert in the beta 1.2 mRNA
      isoform of the voltage gated sodium channel is an intron. Transcripts still
      retaining this intron were detected in all tissues where the beta 1 gene
      expression was investigated. We also show that the exon/intron boundaries of the
      last two introns are conserved among rat, mouse and human beta 1 gene. Unlike the
      highly conserved cDNAs, introns in only the rat and mouse genes are highly
      related. The last intron is very short (86-90 bp) and is located in the 3'
      untranslated sequence, both uncommon properties of mammalian pre-mRNA introns.

PMID- 8549782
TI  - Expression of synaptobrevin II, cellubrevin and syntaxin but not SNAP-25 in
      cultured astrocytes.
AB  - Astrocytes, a sub-type of glial cell in the central nervous system, can release
      the excitatory transmitters glutamate and aspartate in response to elevated
      levels of internal calcium. To investigate potential release mechanisms that may
      be present in these cells we have determined whether protein components of the
      neuronal secretory apparatus are expressed in astrocytes. Western blots,
      immunocytochemistry and RT PCR demonstrate that astrocytes express cellubrevin,
      synaptobrevin II and syntaxin, proteins known to form a macromolecular fusion
      complex. However, SNAP-25 which is another neuronal protein of the fusion
      complex, was not detected. Astrocyte cellubrevin and synaptobrevin II were also
      shown to be sensitive to the proteolytic activity of tetanus toxin. Together
      these data indicate that astrocytes express some proteins that are known to form
      a fusion complex indicating that regulated exocytosis might mediate calcium
      regulated transmitter release from these cells.

PMID- 8549783
TI  - Lipoprotein(a) stimulates the proliferation of cultured human arterial smooth
      muscle cells through two pathways.
AB  - We investigated the effect of lipoprotein(a) (Lp(a)) on proliferation of human
      arterial smooth muscle cells (SMCs) and its mechanisms of action. Low density
      lipoprotein (LDL), Lp(a) and apolipoprotein(a) (apo(a)) significantly stimulated
      the proliferation of SMCs. Lp(a) and apo(a) reduced the amount of active
      transforming growth factor-beta (TGF-beta) with the mink lung epithelial cell
      bioassay, however LDL had no effect. Lp(a), but not apo(a), significantly
      stimulated the proliferation of SMCs even in the presence of a neutralizing
      antibody for TGF-beta. Our results suggest that Lp(a) stimulates the
      proliferation of SMCs via apo(a)-induced inhibition of TGF-beta activation and
      stimulation of SMCs by the LDL-particle of Lp(a).

PMID- 8549784
TI  - Thrombopoietin induces activation of at least two distinct signaling pathways.
AB  - Thrombopoietin (Tpo) is a cytokine regulating megakaryocyte maturation and
      platelet formation. We studied Tpo-induced signal transduction, and found that
      Tpo induces phosphorylation of adapter molecules. Shc and Vav, and of
      serine/threonine kinases Raf-1 and mitogen-activated protein (MAP) kinases.
      Further, Tpo induced activation of Ras, MAP kinase kinase, MAP kinase and Pim-1.
      Taken together with other observations, we concluded that Tpo induces the
      activation of at least two distinct signaling pathways, a specific Tyk2
      JAK2/STAT1-STAT3-STAT5 signaling cascade and a common Shc/Vav/Ras/Raf-1/MAP
      kinase kinase/MAP kinase signaling cascade.

PMID- 8549785
TI  - The molecular motion of bacteriorhodopsin mutant D96N in the purple membrane.
AB  - We measured the flash-induced absorption anisotropies of mutant bacteriorhodopsin
      (bR), D96N, in the purple membrane suspension. The measured anisotropy decay at
      410 nm differed from that at 570 nm. These wavelength-dependent anisotropies show
      that the motion of absorption dipole of non-excited bR is faster than that of M
      intermediate. The motion of non-excited bR is considered as the rotational motion
      of whole protein in the purple membrane. This fact suggests that the photo
      excitation induces the conformational change of the protein and/or the inter
      protein interaction within the membrane, which prevents the motion of M
      intermediate.

PMID- 8549786
TI  - Protein disulfide isomerase mutant lacking its isomerase activity accelerates
      protein folding in the cell.
AB  - We investigated the effect of protein disulfide isomerase (PDI) on in vivo
      protein folding of human lysozyme (h-LZM) in a specially constructed yeast
      coexpression system. Coexpression with PDI increased the amounts of intracellular
      h-LZM with the native conformation, leading to an increase in h-LZM secretion.
      The results indicated that PDI is a real catalyst of protein folding in the cell.
      The secretion of h-LZM increased even when both active sites of PDI were
      disrupted, suggesting that the effect of PDI resulted from a function other than
      the formation of disulfide bonds. This is the first finding that PDI without
      isomerase activity accelerates protein folding in vivo.

PMID- 8549787
TI  - Evidence for the high-spin heme iron in both stable and unstable reduced forms of
      lactoperoxidase: low-temperature magnetic circular dichroism data.
AB  - The unstable and stable ferrous lactoperoxidase at pH 6.0, 7.0 and 10.2 have been
      analysed using optical absorption and variable temperature MCD spectroscopy. The
      evidence is given that two high-spin forms of ferrous. LPO are always observed
      when the enzyme is reduced in a buffer-glycerol mixture at low temperature (ca. 
      20 degrees C) at which no spectral changes are seen for a long time after the
      reduction. Form 1 (the absorption band, 450 nm) dominates significantly over form
      2 (the absorption band, 435 nm), but a relative content of form 2 increases on
      lowering the pH value. An annealing of the unstable LPO at high temperatures is
      followed by complete irreversible conversion of form 1 to form 2. In addition, at
      least one low-spin ferrous form exists in temperature-dependent equilibrium with
      the high-spin form(s) in both stable and unstable ferrous LPO. The reversible
      increase of its content is observed at least down to 140 K, suggesting that minor
      structural changes are sufficient for reaching the heme iron by a distal amino
      acid residue (presumably a histidine).

PMID- 8549788
TI  - Interleukin-10 induces interleukin-11 responsiveness in human myeloma cell lines.
AB  - Interleukin (IL)-6-dependent human myeloma cell lines (HMCL) can be reproducibly
      obtained from patients with multiple myeloma and terminal disease. The growth of
      some of these HMCL can also be supported by IL-11. We show that IL-11-responsive,
      but not -unresponsive, HMCL expressed the gene of human IL-11 receptor (IL-11R)
      and produced an autocrine IL-10. All HMCL expressed the IL-10 receptor. In
      addition, IL-10 induced IL-11R gene expression and conferred IL-11 responsiveness
      on unresponsive HMCL. The ability of HMCL to produce IL-10 was strictly
      correlated with the capacity of the original patient's myeloma cells to produce
      IL-10 or not, and with the presence or absence of IL-10 in the patient's plasma.

PMID- 8549789
TI  - Molecular analysis of the sheep cathelin family reveals a novel antimicrobial
      peptide.
AB  - Cathelin-related genes are characterized by the presence of a prepro sequence
      which is highly conserved both within and between species. 3' RACE analysis on
      sheep bone marrow RNA, using a primer based on a conserved cathelin family coding
      region, demonstrated the presence of at least three ovine cathelin-related cDNAs.
      One of these encodes a novel prepropeptide with a predicted C-terminal cleavage
      product RGLRRLGRKIAHG-VKKYGPTVLRIIRIAG. The chemically synthesized form of this
      29 amino acid peptide is shown to be a thermostable, broad spectrum, bactericidal
      agent.

PMID- 8549790
TI  - Induction of volatile biosynthesis in the lima bean (Phaseolus lunatus) by
      leucine- and isoleucine conjugates of 1-oxo- and 1-hydroxyindan-4-carboxylic
      acid: evidence for amino acid conjugates of jasmonic acid as intermediates in the
      octadecanoid signalling pathway.
AB  - One of the most intriguing plant defense reactions against herbivores is the
      emission of volatiles as potentially attractive signals for the natural enemies
      of the attacking species. Like many other low and high molecular weight chemical
      defenses, volatile production is under the control of the octadecanoid signalling
      pathway leading to jasmonic acid (2) (threshold concentration of jasmonic acid
      giving rise to volatile induction in Phaseolus lunatus: approximately 100 nmol.ml
      1). A significantly more active compound is the phytotoxin coronatine (3)
      (threshold concentration: > or = 1 nmol.ml-1). Methyl esters of 1-oxo-indanoyl
      isoleucine (4) or 1-oxo-indanoyl-leucine (5), designed as readily available
      analogues of coronatin (3), have also been shown to be active (threshold
      concentration: > or = 20 nmol.ml-1). Crucially, their component parts, i.e. 1-oxo
      indan-carboxylic acid and the amino acids are completely inactive. The pattern of
      emitted volatiles, produced by plants treated with these analogues, is largely
      identical to that released from coronatine- or jasmonic acid-treated plants.
      While the reduction of the carbonyl group of jasmonic acid (2) results in an
      inactive molecule, namely curcurbic acid, the methyl ester of the 1-hydroxy
      indanoyl-isoleucine conjugate (8) is at least as effective as the corresponding
      oxo-derivatives (4) and (5) (threshold concentration: > or = 20 nmol.ml-1). The
      results support the concept that epi-jasmonic acid (1) may be converted into a
      leucine or isoleucine conjugate at an early stage in the natural signal
      transduction pathway. Their later interaction with a macromolecular receptor
      apparently requires enolization of the carbonyl group in the jasmonate moiety,
      yielding a planar segment which is essential for successful binding with the
      macromolecule. The resulting hydroxy group is implicated in the formation of a
      hydrogen bond in the ensuing ligand/receptor complex.

PMID- 8549791
TI  - Identification and purification of a bovine liver mitochondrial NAD(+)
      glycohydrolase.
AB  - Nonenzymatic ADP-ribosylation of mitochondrial proteins is thought to play a role
      in the regulation of Ca2+ efflux from mitochondria. It has been shown that
      intramitochondrial ADP-ribose is generated by a specific NAD(+)glycohydrolase,
      which catalizes hydrolysis of NAD+ to ADP-ribose and nicotinamide. We purified
      this enzyme from bovine liver mitochondrial membranes. The final preparation had
      a 1660-fold purified enzyme activity and contained a main protein band with an
      apparent molar mass of 32,000 in a SDS-polyacrylamide gel. The identity of this
      protein band with NAD(+)-glycohydrolase was verified by renaturation of its
      enzymatic activity. Partial amino acid sequence information was obtained from two
      enzyme fragments after proteolytic cleavage of the protein band in the SDS
      polyacrylamide gel. Searches in protein databases revealed that an arginine ADP
      ribosyl hydrolase harbours two stretches of amino acids that are highly similar
      to the partial NAD(+)-glycohydrolase sequences.

PMID- 8549792
TI  - Adenosine evokes potassium currents by protein kinase C activated via a novel
      signaling pathway in superior colliculus neurons.
AB  - Adenosine evoked whole-cell potassium currents and enhanced intracellular free
      Ca2+ concentration ([Ca2+]i) in superior colliculus neurons through a P2Y
      purinoceptor linked to a pertussis toxin-insensitive G-protein, possibly Gq
      protein, which is involved in a protein kinase C (PKC) activation pathway. The
      [Ca2+]i increase was inhibited by a phospholipase C (PLC) inhibitor, whereas the
      evoked currents were not affected by a PLC inhibitor or a phospholipase A2 (PLA2)
      inhibitor. Adenosine elicited single channel currents via PKC activation in cell
      attached patches and furthermore, those currents with conductances of the same
      slope were induced even in excised patches, suggesting that PKC can be activated
      only by cell membrane factors without intracellular components. These results
      thus indicate that the P2Y purinoceptor-coupled potassium channel is regulated
      via a novel PKC activation pathway independent of PLC or PLA2.

PMID- 8549793
TI  - M-caveolin, a muscle-specific caveolin-related protein.
AB  - Caveolae, small invaginations of the plasma membrane, are a characteristic
      feature of many mammalian cells. The best-characterised caveolar protein is the
      integral membrane protein, VIP21-caveolin. We now describe a novel homologue of
      VIP21-caveolin, M-caveolin, which is expressed exclusively in muscle. M-caveolin
      was shown to be expressed in differentiated myotubes but not myoblasts. Epitope
      tagged M-caveolin expressed in non-muscle cells was targetted to surface caveolae
      where it colocalized with endogenous VIP21-caveolin. M-caveolin may play a
      specialised role in the caveolae of muscle cells.

PMID- 8549794
TI  - Unfarnesylated transforming Ras mutant inhibits the Ras-signaling pathway by
      forming a stable Ras.Raf complex in the cytosol.
AB  - Farnesyltransferase inhibitors cause the growth arrest of ras-transformed cells,
      but not that of normal cells. To elucidate the mechanism of this differential
      effect, we examined the effect of accumulation of unfarnesylated Ras in the
      cytosol by using RasG12V,C186S and RasC186S, which mimic unfarnesylated form of
      the oncogenic and the normal Ras, respectively. We found that RasG12,C186S
      inhibited activation and membrane translocation of Raf by forming a stable
      complex with Raf in the cytosol. In contrast, RasC186S showed inhibitory effect
      on neither Raf activation nor Raf translocation. These results indicate that
      unfarnesylated oncogenic Ras interacts with Raf in the cytosol and inhibits its
      membrane translocation, a crucial step for the Raf activation, while
      unfarnesylated normal Ras does not.

PMID- 8549795
TI  - Isolation of an ion channel gene from Arabidopsis thaliana using the H5 signature
      sequence from voltage-dependent K+ channels.
AB  - A degenerate oligonucleotide corresponding to the K+ channel signature sequence
      (TMTTVGYGD) was used to isolate the genomic and cDNA forms of a new channel gene,
      AKT3, from Arabidopsis thaliana. The deduced protein sequence has a predicted
      membrane topography similar to Shaker-like K+ channels. Three distinct modules
      comprise the carboxyl-terminal half: a nucleotide-binding motif, an ankyrin
      repeat domain, and a polyglutamate track. Xenopus oocytes injected with cRNA
      exhibited an inward-rectifying K+ current, demonstrating that the AKT3
      polypeptide is a functional transport protein. Two other Arabidopsis K+
      transporters (AKT1 and KAT1) share 60% homology with AKT3; together these
      proteins constitute a family of plant inward-rectifying K+ channels.

PMID- 8549796
TI  - Differential effects of NaCl concentration on the constitutive activity of the
      thyrotropin and the luteinizing hormone/chorionic gonadotropin receptors.
AB  - The TSH receptor (TSHR) and the LH/CG receptor (LHR) are members of the family of
      G protein-coupled receptors. Recently, point mutations conferring constitutive
      activity to the TSHR and LHR have been observed as a cause of toxic adenoma and
      familial/sporadic male pseudo-precocious puberty, respectively. When evaluated by
      transfection in COS-7 cells the wild-type (wt) TSHR displays definite
      constitutive activity towards Gs-dependent adenylylcyclase stimulation, while
      available evidence shows that the LHR does not. In order to compare the
      constitutive activity of both receptors, we performed functional studies in COS-7
      cells using different assay conditions. Human TSHR and LHR cDNAs subcloned in the
      expression vector pSVL were transiently expressed in COS-7 cells and cAMP
      production was determined following incubation in a medium containing
      physiological concentration of NaCl [isotonic (NaCl)] or in the same medium
      without NaCl [hypotonic (NaCl-)] or where NaCl was replaced by an isoosmolar
      concentration of sucrose [isotonic (sucrose)]. Cells transfected with the TSHR
      showed higher basal cAMP levels over cells transfected with pSVL in all
      conditions tested. The effect was stronger when cells were incubated in isotonic
      (sucrose) buffer. Cells expressing LHR exhibited a minimal increase of cAMP
      levels over cells transfected with pSVL in isotonic (NaCl) buffer; however, a
      marked increase in basal cAMP levels was observed when cells were assayed in
      hypotonic (NaCl-) or isotonic (sucrose) buffers. Varying the pH or incubation
      temperature was without effect on the results obtained with both receptors. Our
      data show that despite extensive sequence similarity, the LH and TSH receptors
      differ markedly in their basal activity. The differential sensitivity of both
      receptors to low NaCl concentrations, suggests that the unliganded TSH receptor
      is less constrained than its LH homolog and may be more susceptible to activation
      by a wide spectrum of mutations.

PMID- 8549797
TI  - Effects of temperature shifts on the activities of Neurospora crassa glycogen
      synthase, glycogen phosphorylase and trehalose-6-phosphate synthase.
AB  - Conidiospore germlings of Neurospora crassa submitted to a heat shock at 45
      degrees C accumulate trehalose and degrade glycogen. The opposite occurs upon
      reincubation at a physiologic temperature (30 degrees C). These observations
      suggest a temperature-dependent mechanism for the preferential synthesis of one
      or the other sugar reserve. Here we show that concomitant with these shifts of
      temperature, occurred reversible changes in the activities of glycogen synthase
      and phosphorylase. Glycogen synthase was inactivated at 45 degrees C while
      phosphorylase was activated. The reverse was true when the cells were shifted
      back to 30 degrees C. Addition of cycloheximide did not prevent the reversible
      enzymatic changes, which remained stable after gel filtration. Apparently, the
      effects of temperature shifts occurred at the level of reversible covalent
      enzymatic modifications. Trehalose-6-phosphate synthase properties were also
      affected by temperature. For instance, the enzyme was less sensitive to in vitro
      inhibition by inorganic phosphate at 50 degrees C than at 30 degrees C. Fructose
      6-phosphate partially relieved the inhibitory effect of phosphate at 30 degrees C
      but not at 50 degrees C. These effects of the assay temperature, inorganic
      phosphate, and fructose-6-phosphate, on trehalose-6-phosphate synthase activity,
      were more evident for crude extracts obtained from heat-shocked cells.
      Altogether, these results may contribute to explain the preferential accumulation
      of trehalose 45 degrees C, or that of glycogen at 30 degrees C.

PMID- 8549799
TI  - Spectroscopic study of an HIV-1 capsid protein major homology region peptide
      analog.
AB  - The capsid (CA) domain of retroviral Gag proteins possesses one subdomain, the
      major homology region (MHR), which is conserved among nearly all avian and
      mammalian retroviruses. While it is known that the mutagenesis of residues in the
      MHR will impair virus infectivity, the precise structure and function of the MHR
      is not known. In order to obtain further information on the MHR, we have examined
      the structure of a synthetic peptide encompassing the MHR of human
      immunodeficiency virus type I (HIV-1) CA protein. Multiple sequence alignment and
      secondary structure prediction indicate that the peptide could form 50% alpha
      helix and 10% beta-sheet. In addition, circular dichroism studies indicate that,
      in the presence of 50% trifluoroethanol (TFE), the peptide adopts an alpha
      helical structure over half of its length. Further analysis by proton nuclear
      magnetic resonance spectroscopy suggests that the C-terminal portion of the MHR
      forms a helix in aqueous solution. Upon the addition of TFE, the position of the
      helix remains nearly constant, but the magnitude of the changes in H alpha
      chemical shifts of the residues indicate a more stable helix. These results
      suggest that a helical C-terminus of retroviral MHRs may be integral to the
      function of this region.

PMID- 8549798
TI  - Enzymatic characterization of purified NS3 serine proteinase of hepatitis C virus
      expressed in Escherichia coli.
AB  - Non-structural protein 3 (NS3) of the hepatitis C virus (HCV) has been shown to
      be a serine proteinase which cleaves the HCV polyprotein thus activating its
      replicative machinery. To characterize enzymatic activities of NS3 serine
      proteinase, the proteinase region was expressed in Escherichia coli and purified.
      The purified proteinase specifically cleaved a purified fusion protein
      sandwiching the NS5A/5B cleavage sequence. In addition to serine proteinase
      inhibitors, some chelators also inhibited the cleavage activity. Metal ions were
      not required for its activity, suggesting that the proteinase may be a novel
      serine proteinase having a unique binding site for chelators.

PMID- 8549800
TI  - A novel yeast protein showing specific association with the cyclin-dependent
      kinase 5.
AB  - The present study describes a significant amino acid sequence homology between
      neuronal Cdk5 activator (nck5a) and an open reading frame of an unknown gene on
      the yeast S. cerevisiae chromosome III. A cDNA encoding a 25 kDa fragment of this
      yeast protein, the region containing homologous sequence to nck5a was cloned and
      expressed in E. coli as a glutathine-S-transferase fusion protein (GST-p25Y). GST
      p25Y was found to block the in vitro activation of Cdk5 by nck5a and to affinity
      precipitate Cdk5 from bovine brain extract. The observations indicate that the
      yeast protein is capable of specific and high affinity association with Cdk5.

PMID- 8549801
TI  - Effect of potential binding site overlap to binding of cellulase to cellulose: a
      two-dimensional simulation.
AB  - A computer simulation model for the binding of ligands to a totally anisotropic
      surface (infinite two-dimensional square lattice) with overlapping binding sites
      has been developed. The validity of the simulation has been proven by comparison
      with cases where the correct results are known. The simulation of kinetics shows
      that when the lattice is close to saturation, the true equilibrium state is
      reached extremely slowly due to a lot of rearranging of the ligands on the
      lattice. Based on these findings, the terms 'apparent saturation' and 'apparent
      maximum coverage' have been introduced and defined. The largest discrepancies
      between 'apparent maximum coverage' and the theoretically predicted value were
      observed for ligands of large size and/or irregular shape. As an example, the
      model has been applied to describe the binding of cellobiohydrolase-I core to
      Avicel. A formula for calculation of the intrinsic binding constant, maximal
      binding capacity and specific surface of cellulose from real binding data has
      been derived.

PMID- 8549802
TI  - Cloning and tissue expression of two cDNAs encoding the peroxisomal 2-enoyl-CoA
      hydratase/3-hydroxyacyl-CoA dehydrogenase in the guinea pig liver.
AB  - The 2-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD) is the second
      enzyme of the peroxisomal beta-oxidation pathway. In human and rat, only one HD
      mRNA has been so far detected in the liver. This paper reports for the first time
      in a mammal species, the guinea pig, the cloning and sequencing of two cDNAs
      encoding an HD. The 3,274 nucleotide-cDNA is a strictly identical but longer copy
      of the 2,494 nucleotide-form. A 2,178 bp-open reading frame encodes a protein of
      726 amino acids (M(r) 79.3 kDa) with the peroxisomal-targeting signal (tripeptide
      SKL) at the carboxyterminus. Northern blot analysis of HD mRNA identified three
      mRNAs of respective sizes 3.5, 2.6 and 1.6 kb in the guinea pig liver and
      kidneys.

PMID- 8549803
TI  - A growth inhibitor implicated in the growth arrest of human fibroblasts.
AB  - When quiescent human fibroblasts are induced to divide, the sugar composition of
      a growth inhibitory glycoprotein is modified. The kinetics of the incorporation
      of glucosamine in the growth inhibitor follows the kinetics of cell growth. It
      increases as cells approach quiescence and declines when cells initiate
      proliferation. The results suggest that the modification of the sugar composition
      of this glycoprotein is coupled with the variation of its inhibitory potential
      and this way to the initiation and the arrest of cell division.

PMID- 8549804
TI  - Dominant negative chimeras provide evidence for homo and heteromultimeric
      assembly of inward rectifier K+ channel proteins via their N-terminal end.
AB  - Chimeras have been constructed using three different fragments (N-terminal,
      central and C-terminal) of IRK3, a constitutive inward rectifier K+ channel
      subunit, and GIRK2, a G-protein activated inward rectifier K+ channel subunit and
      have been coinjected into Xenopus oocytes together with IRK3 or IRK1 (another
      constitutive inward rectifier) cRNA. Both IRK1 and IRK3 expression was inhibited
      by coinjection with chimeras containing a N-terminal fragment of IRK3 suggesting
      that subunits of K+ channels in the IRK family form a functional multimeric
      assembly where the N-terminal end has an important role. In situ hybridization
      shows that IRK1 and IRK3 are coexpressed in the same areas of the brain and
      probably in the same cells. Taken together both the localization and the oocyte
      expression results suggest that not only homomultimeric IRK1 or homomultimeric
      IRK3 assemblies take place but that heteromultimeric IRK1/IRK3 assemblies are
      also formed.

PMID- 8549805
TI  - High-level expression of fully active human glutaredoxin (thioltransferase) in E.
      coli and characterization of Cys7 to Ser mutant protein.
AB  - Glutaredoxin (Grx) (12 kDa) is a hydrogen donor for ribonucleotide reductase and
      also a general GSH-disulfide reductase of importance for redox regulation. To
      overexpress human glutaredoxin in Escherichia coli, a cDNA encoding human Grx was
      modified and cloned into the vector pET-3d and expressed in E. coli BL21 (DE3) by
      IPTG induction. High-level expression of Grx was verified by GSH-disulfide
      oxidoreductase activity, SDS-PAGE and immunoblotting analysis. The recombinant
      human Grx in its reduced form was purified to homogenity with 50% yield and
      exhibited the same dehydroascorbate reductase and hydrogen donor activity for
      ribonucleotide reductase (Km approximately 0.2 microM) as the human placenta
      protein. Human Grx contains a total of 5 half-cystine residues including a non
      conserved Cys7 residue and is easily oxidized to form dimers during storage. A
      Grx mutant Cys7 to Ser was generated by site-directed mutagenesis and the protein
      was purified to homogeneity. The mutant protein showed full activity and
      exhibited a much reduced tendency to form dimers compared with the wild type
      protein. Peptide sequencing confirmed the mutation and removal of the N-terminal
      Met residue in both wild type and mutant proteins. Fluorescence spectra
      demonstrated only tyrosine fluorescence in human Grx with a peak at 310 nm which
      increased 20% upon reduction and decreased by addition of GSSG demonstrating that
      glutathione-containing disulfides are excellent substrates.

PMID- 8549806
TI  - Molecular cloning and characterization of Byp, a murine receptor-type tyrosine
      phosphatase similar to human DEP-1.
AB  - Novel murine cDNAs encoding a receptor-like protein tyrosine phosphatase, termed
      Byp (HPTP beta-like tyrosine phosphatase) were cloned. The putative Byp protein
      consists of 1238 amino acids, which possesses a single catalytic domain in the
      cytoplasmic region. The extracellular region comprises eight repeats of a
      fibronectin type III module and contains multiple N-glycosylation sites. The byp
      mRNA was 7.7-kb long and expressed in every tissue examined, its level being high
      in the brain and kidney. Transfection of the byp cDNA expression plasmid into
      COS7 cells resulted in the expression of a 220-kDa tyrosine phosphorylated
      protein. Furthermore, co-expression of Byp and the Src family kinase Fyn
      increased the level of tyrosine phosphorylation of Byp, suggesting that Byp was
      tyrosine-phosphorylated by Fyn. Finally, the byp gene was located to mouse
      chromosome 2E1-2 and rat chromosome 3q32-33.

PMID- 8549807
TI  - Gastrin induces tyrosine phosphorylation of Shc proteins and their association
      with the Grb2/Sos complex.
AB  - Gastrin/CCKB G protein-coupled receptors have been shown to mediate proliferative
      effects of their endogenous ligands. In the present study, we examined the signal
      transduction mechanisms linked to the G/CCKB receptor occupancy. We report here
      that gastrin stimulates MAP kinase activation in a dose- and time-dependent
      manner, a pathway known to play a key role in cell proliferation. We also
      characterized the molecular events, upstream of p21-Ras, that may link the MAP
      kinase pathway to G/CCKB receptors. Gastrin induced a rapid and transient
      increase in tyrosine phosphorylation of several proteins including the 2 isoforms
      (46 and 52 kDa) of the adaptor protein Shc. Phosphorylated Shc subsequently
      associated with a complex that includes Grb2 and the p21-Ras activator, Sos. Our
      results also indicate that Sos becomes phosphorylated in response to gastrin as
      shown by a reduction in electrophoretic mobility of the protein. Tyrosine
      phosphorylation of Shc and subsequent complex formation with Grb2 and Sos appear
      to be a common mechanism by which tyrosine kinase receptors and the G/CCKB G
      protein-coupled receptor stimulate the Ras-dependent MAP kinase pathway.

PMID- 8549808
TI  - RGD induces conformational transition in purified platelet integrin GPIIb/IIIa
      SDS system yielding multiple binding states for fibrinogen gamma-chain C-terminal
      peptide.
AB  - Fibrinogen gamma-chain C-terminal peptide HHLG-GAKQAGDV (gamma 12) and alpha
      chain peptide GRGDSP are known to inhibit fibrinogen-mediated platelet cell
      aggregation via competitive interactions with platelet integrin receptor
      GPIIb/IIIa. NMR studies of gamma 12 in the presence of purified GPIIb/IIIa in
      SDS/water solution have demonstrated the presence of two gamma 12 binding states,
      one of which is eliminated by GRGDSP (RGD) up to a RGD: gamma 12 ratio of 2:1.
      RGD: gamma 12 ratios greater than 2:1 produce multiple sets of gamma 12 NMR
      signals in TOCSY spectra. At a ratio of 4:1, two to four such resonance sets can
      be resolved for A405, Q407, A408, G409, D410 and V411 spin systems. The number of
      multiple resonances remains unchanged at ratios of 6:1 and 8:1. Addition of gamma
      12 to reverse the ratio to 8:8 (1:1) has no apparent effect on the RGD-induced
      distribution. Results suggest that RGD irreversibly induces a conformational
      transition(s) in GPIIb/IIIa to produce multiple gamma 12 binding sites on the
      receptor.

PMID- 8549809
TI  - Adrenomedullin stimulates DNA synthesis and cell proliferation via elevation of
      cAMP in Swiss 3T3 cells.
AB  - Our results demonstrate that the novel vasoactive regulatory peptide
      adrenomedullin is a potent mitogen for Swiss 3T3 cells. Acting via a specific
      adrenomedullin receptor, it stimulates a dose-dependent increase in DNA synthesis
      in synergy with insulin. Additionally, adrenomedullin stimulates further
      progression through the cell cycle resulting in cell proliferation, an effect
      that was further enhanced by the presence of insulin. Adrenomedullin rapidly
      induces accumulation of intracellular cAMP but does not stimulate an increase in
      intracellular Ca2+, activation of protein kinase C, or tyrosine phosphorylation
      of intracellular substrates. Adrenomedullin-stimulated mitogenesis is markedly
      enhanced in Swiss 3T3 cells stably transfected with a constitutively activated Gs
      alpha, which are highly sensitive to agents that elevate cAMP, and is inhibited
      by the PKA inhibitor H-89. Adrenomedullin is, thus, identified as a novel
      mitogenic regulatory peptide acting via cAMP.

PMID- 8549810
TI  - The vitamin D3 analogue, calcipotriol, induces sphingomyelin hydrolysis in human
      keratinocytes.
AB  - The possible role of sphingomyelin cycle for the regulation of cell proliferation
      was investigated in human keratinocytes. The time-dependent breakdown of
      sphingomyelin was observed in the immortalized human keratinocyte cell line HaCaT
      as well as in primary human keratinocytes thereby providing evidence that the
      sphingomyelin cycle might be of importance in the epidermis. Peak levels of 20
      30% sphingomyelin hydrolysis were measured 3 h after treatment of the cells with
      1 alpha,25-dihydroxyvitamin D3 or with the vitamin D3 analogue, calcipotriol. The
      decrease of sphingomyelin upon addition of vitamin D3 or calcipotriol was
      accompanied by an approximately 70% increase of ceramide in the cells. The
      effects of vitamin D3 and calcipotriol on sphingomyelin breakdown were paralleled
      by their antiproliferative potency. Furthermore, the cell-permeable ceramide, N
      acetylsphingosine, and natural ceramide inhibited cell proliferation of human
      keratinocytes. The results presented suggest that induction of the sphingomyelin
      cycle represents one mechanism mediating the therapeutic effect of calcipotriol
      in treatment of psoriasis.

PMID- 8549811
TI  - A sequence analysis of the beta-glucosidase sub-family B.
AB  - This computational study is a summary of structural properties of the beta
      glucosidase subfamily B. Computations were carried out using GCG package
      programs. All sequences used in this analysis were taken from the protein data
      bank. The multialignment and the phylogenetic tree of the beta-glucosidase sub
      family B are shown. The conserved patterns: DGP, GRNFE, DPYL, KHF, SDW, GLD,
      VLLKN in the N-terminal region and FGYGLSY in the C-terminal part should be
      pointed out. C-terminal parts of the Butyrivibrio fibrisolvens and Ruminoccocus
      albus beta-glucosidase sequences can be aligned to the N-terminal region of the
      other members of the subfamily. A crossed homology model in sub-family B beta
      glucosidases is described.

PMID- 8549812
TI  - Crystallisation of the Bacillus subtilis sporulation inhibitor SinR, complexed
      with its antagonist, SinI.
AB  - The transcription factor SinR, a pleiotropic regulator of late growth processes
      in Bacillus subtilis, has been crystallised as a complex with its antagonist
      SinI, in a form suitable for structural analysis. The SinI:SinR crystals diffract
      X-rays generated from a rotating copper anode source to 2.3 A spacing and a
      complete native dataset has been collected to this resolution limit. The space
      group of the crystals is P3(1)21 (or its enantiomorph P3(2)21) with cell
      dimensions a = b = 60.76 A, c = 87.79 A. Assuming that there is a single
      SinI:SinR heterodimer in the asymmetric unit, the crystals have a Vm of 2.53
      A3.Da-1.

PMID- 8549813
TI  - Control of apoptosis by the cellular ATP level.
AB  - Apoptosis is a physiological form of cell death. Its causes and execution
      mechanisms are not clearly understood. Oxidative stress, nitric oxide and its
      congeners, Ca2+, proteases, nucleases, and mitochondria are considered mediators
      of apoptosis. At present their importance and exact role are elusive but it is
      clear that mitochondria are both the target and the source of oxidative stress,
      nitric oxide, and Ca2+. The mitochondrial membrane potential (delta psi), which
      is the driving force for mitochondrial ATP synthesis, declines during apoptosis,
      and maintenance of delta psi prevents apoptosis. Since apoptosis is highly
      regulated and involves the activity of hydrolytic enzymes, chromatin condensation
      and vesicle formation apoptosis is likely to have a high energy demand. We
      propose that the cellular ATP level is an important determinant for cell death.
      This hypothesis is supported by circumstantial evidence, is consistent with the
      available data, has a corrolary in aging, and is amenable to direct experimental
      testing particularly with flow cytometry as a promising tool.

PMID- 8549814
TI  - S-nitrosoglutathione induces formation of nitrosylmyoglobin in isolated hearts
      during cardioplegic ischemia--an electron spin resonance study.
AB  - Previously, it has been shown that *NO donor S-nitrosoglutathione (GSNO) improves
      the postischemic functional recovery in crystalloid buffer-perfused isolated rat
      hearts subjected to cardioplegic ischemia. Supplementation of cardioplegic
      solution with nitronyl nitroxide, a scavenger of *NO, antagonized this protective
      effect. Using low temperature ESR, we have detected nitrosylmyoglobin (MbNO) in
      rat hearts subjected to cardioplegic ischemia in the presence of GSNO (20-200
      mumol/l). During aerobic reperfusion MbNO signal intensity gradually decreased,
      but persisted for up to 30 min of aerobic reperfusion. We conclude that MbNO is
      an endogenous marker of *NO release in myocardial tissues. Implications of MbNO
      formation are discussed with respect to cardioprotection during ischemia- and
      reperfusion-induced myocardial injury.

PMID- 8549815
TI  - DNA-binding sperm proteins with oligo-arginine clusters function as potent
      activators for egg CK-II.
AB  - The stimulatory effect of DNA-binding sperm proteins (histone and protamine) on
      the phosphorylation of p98 (ERp99/GRp94, one of the Hsp-90 family of proteins) by
      egg casein kinase II (CK-II) was investigated in vitro. It was found that (i)
      phosphorylation of p98 by egg CK-II in vitro is greatly stimulated by poly-Arg,
      but not by poly-Lys; and (ii) similar stimulation is observed with sperm histones
      H2B2 and H2B3 (sea urchin) and fish protamines, such as salmine A1 (salmon) and
      protamine 3a (rainbow trout). These findings suggest that these DNA-binding sperm
      proteins function as potent activators for CK-II in fertilized eggs. All of these
      DNA-binding sperm proteins contain at least an oligo-Arg cluster as a common
      feature, which can interact with an acidic amino acid cluster of the regulatory
      beta-subunit CK-II.

PMID- 8549816
TI  - Ca(2+)-dependent inactivation of the class C L-type Ca2+ channel is a property of
      the alpha 1 subunit.
AB  - The stably expressed Ca2+ channel alpha 1C-a and alpha 1C-b subunit were used to
      investigate the molecular basis for Ca(2+)-dependent inactivation of the L-type
      current. The Ba2+ current (IBa) of both channels had similar kinetics and
      inactivated with one time constant of about 400 ms at +20 mV, whereas the Ca2+
      current (ICa) could be fitted only with a bi-exponential function. The fast (tau
      f) and the slow (tau s) time constant were about 20 ms and 400 ms, respectively.
      The inactivation of ICa strongly depended on the entry of Ca2+ as shown by
      prepulses and variation of the intracellular Ca2+ chelator. Coexpression of the
      alpha 1C subunits with the auxiliary alpha 2/delta and beta subunits accelerated
      the voltage-dependent but not the Ca(2+)-dependent inactivation of the channels.
      These results suggest that the alpha 1C subunit of L-type Ca2+ channels itself
      mediates the Ca(2+)-dependent inactivation of the current.

PMID- 8549817
TI  - The C-terminal (haemopexin-like) domain structure of human gelatinase A (MMP2):
      structural implications for its function.
AB  - In common with most other matrix metalloproteinases, gelatinase A has a non
      catalytic C-terminal domain that displays sequence homology to haemopexin.
      Crystals of this domain were used by molecular replacement to solve its molecular
      structure at 2.6 A resolution, which was refined to an R value of 17.9%. This
      structure has a disc-like shape, with the chain folded into a beta-propeller
      structure that has pseudo four-fold symmetry. Although the topology and the side
      chain arrangement are very similar to the equivalent domain of fibroblast
      collagenase, significant differences in surface charge and contouring are
      observable on 1 side of the gelatinase A disc. This difference might be a factor
      in allowing the gelatinase A C-terminal domain to bind to natural inhibitor TIMP
      2.

PMID- 8549818
TI  - An isochorismate hydroxymutase isogene in Escherichia coli.
AB  - The pivotal step in enterobactin and menaquinone biosynthesis is the conversion
      of chorismate to isochorismate. Circumstantial evidence pointed to Escherichia
      coli isochorismate hydroxymutase isogenes being responsible for this conversion.
      While the gene involved in enterobactin synthesis (entC) was known, the
      corresponding gene for menaquinone biosynthesis (menF) was not but has now been
      identified and sequenced. The amino acid sequence of MenF is 23.5% identical and
      57.8% similar to that of EntC.

PMID- 8549819
TI  - Identification of a novel protein containing two C2 domains selectively expressed
      in the rat brain and kidney.
AB  - We have isolated and characterized a rat brain cDNA clone which encodes a new
      protein of 474 amino acids in length which contains two C2 domains structurally
      homologous to those present in synaptotagmins. The overall amino acid identity in
      C2 domains between this protein and the synaptotagmins is 36-44%. This protein
      also contains 3 putative consensus sequences for phosphorylation by cAMP
      dependent protein kinase. RNA blot hybridization revealed a 3.0 kb transcript
      abundantly expressed only in the rat brain and the kidney. Thus, we called this
      brain/kidney protein (B/K). In situ hybridization and Northern blot analyses
      showed that the B/K transcript was found in forebrain including the olfactory
      bulb, cerebral cortex, hippocampus, and hypothalamus. In the kidney, high levels
      of B/K transcript were expressed in the papillary region of the inner medulla,
      the inner stripe of the outer medulla and the cortex. The selective expression in
      forebrain and kidney suggests that B/K may be involved in similar cAMP-dependent
      processes at these very different sites.

PMID- 8549820
TI  - Effects of hydrogen/deuterium exchange on photosynthetic water cleavage in PS II
      core complexes from spinach.
AB  - H/D isotope exchange effects on P680+. reduction by Yz and electron abstraction
      from the water oxidizing complex (WOC) in redox state S3 by YZOX were analyzed in
      PS II core complexes from spinach by measurements of laser flash induced
      absorption changes at 820 nm and 355 nm. The results obtained reveal: (1) the
      rate of Yz oxidation by P680+. is almost independent of the substitution of
      exchangeable protons by deuterons; and (2) the reaction between YZOX and the WOC
      in S3 exhibits a kinetic H/D isotope exchange effect of similar magnitude as that
      recently observed in PS II membrane fragments [Renger, G., Bittner, T. and
      Messinger, J. (1994) Biochem. Soc. Trans. 22, 318-322]. Based on these results it
      is inferred that photosynthetic dioxygen formation comprises the cleavage of at
      least one hydrogen bond.

PMID- 8549821
TI  - Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells
      derived from Japanese patients with chronic fatigue syndrome.
AB  - CFS, a recently named heterogeneous disorder, is an illness of unknown etiology.
      The association of CFS with viral infections has been suggested. A common
      association between CFS and several viruses examined has not been confirmed.
      Here, we centered on the possible link between CFS and BDV infection. By nested
      RT-PCR followed by hybridization, BDV RNA was demonstrated as a clear signal in
      PBMCs in 3 out of 25 CFS patients. The amplified cDNA fragments were cloned and
      sequenced. A total of 16 clones were studied. Intra-patients divergencies of the
      p24 were 2-9%, 3-20%, and 3-11% in the deduced amino acids. Inter-patient
      divergencies among the 16 clones were 3-24%. Antibodies to recombinant BDV p24
      protein were detected in 6 CFS patients including one carrying BDV RNA. Overall,
      these gave the prevalence of 32% (8/25) in Japanese CFS patients, suggesting that
      Japanese CFS is highly associated with active infection of BDV, or a related
      agent.

PMID- 8549822
TI  - Opening of the mitochondrial permeability transition pore by uncoupling or
      inorganic phosphate in the presence of Ca2+ is dependent on mitochondrial
      generated reactive oxygen species.
AB  - In this study, we show that mitochondrial membrane permeability transition in
      Ca(2+)-loaded mitochondria treated with carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone (FCCP) or inorganic phosphate (P(i)) is
      preceded by enhanced production of H2O2. This production is inhibited either by
      ethylene glycobis(b-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) or Mg2+,
      but not by cyclosporin A. Permeability transition is prevented either by EGTA,
      catalase or dithiothreitol, suggesting the involvement of Ca2+, H2O2 and
      oxidation of membrane protein thiols in this mechanism. When mitochondria are
      incubated under anaerobiosis, no permeabilization or H2O2 production occurs.
      Based on these results we conclude that mitochondrial permeability transition
      induced by P(i) or FCCP-uncoupling is dependent on mitochondrial-generated
      reactive oxygen species.

PMID- 8549823
TI  - Novel synthetic retinoic acid inhibits rat collagen arthritis and differentially
      affects serum immunoglobulin subclass levels.
AB  - Retinoids affect many biological processes such as cell proliferation,
      differentiation and morphogenesis, but their effects on arthritic patients and
      animal models of arthritis are controversial. We tested the effect of a novel
      synthetic retinoic acid, Am-80 (4-[(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2
      naphthalenyl) carbamoyl] benzoic acid), on type-II collagen (CII)-induced
      arthritis (CIA) in rats. Am-80 markedly suppressed the incidence of arthritis,
      hindpaw swelling and bone destruction. In contrast, 13-cis-retinoic acid (13-cis
      RA) hardly inhibited these CIA symptoms. Moreover, Am-80, but not 13-cis-RA,
      strongly reduced the serum level of anti-CII antibody and differentially affected
      the levels of immunoglobulin (Ig) subclasses in vivo: IgG1 and IgG2a levels were
      decreased, while IgA level was increased without any change in the IgM level.
      These findings indicate that Am-80 may be one of the lead retinoic acids of a new
      class of anti-inflammatory agents.

PMID- 8549824
TI  - Purification and characterization of furostanol glycoside 26-O-beta-glucosidase
      from Costus speciosus rhizomes.
AB  - In plants, spirostanol glycosides (steroid saponins) are known to be formed
      furostanol glycosides during postharvest treatment and storage. Furostanol
      glycoside 26-O-beta-glucosidase (F26G) involved in this conversion was purified
      to apparent homogeneity for the first time from Costus speciosus rhizomes which
      accumulate these glycosides. The enzyme was highly specific for cleavage of the C
      26-boudn glucose moiety of furostanol glycosides showing Km for protogracillin of
      50 microM. Glucono-1,5-lactone, a typical beta-glucosidase inhibitor, and
      diosgenin, an aglycone of spirostanol glycosides, strongly inhibited the enzyme
      activity. The purified F26G is dimeric with a native apparent molecular weight of
      110,000 consisting of subunits of 54,000 and 58,000. The N-terminal sequence of
      the 54,000 protein has a high similarity to the sequences found in N-terminal
      regions of known plant beta-glucosidases.

PMID- 8549825
TI  - Inhibition of the catalytic activity of human transaldolase by antibodies and
      site-directed mutagenesis.
AB  - Transaldolase is a key enzyme of the pentose phosphate pathway. While antibody
      (Ab) 169, directed against the N-terminal 139 residues of human transaldolase
      (TAL-H), had no effect on enzyme activity, Ab 12484 raised against full length
      and functional recombinant TAL-H inhibited catalytic activity. This tentatively
      mapped the catalytic site to the C-terminal 140-336 amino acid portion of TAL-H.
      Dihydroxyacetone transfer reactions catalyzed by transaldolase depend on Schiff
      base formation by a lysine residue. Replacement of lysine-142 by glutamine using
      site-directed mutagenesis resulted in a complete loss of enzyme activity,
      suggesting that lysine-142 is essential for the catalytic activity of TAL-H.

PMID- 8549826
TI  - Enzymatic activity of the ribosome-bound nascent polypeptide.
AB  - Firefly luciferase was shown to be completely folded and thus enzymatically
      active immediately upon release from the ribosome [Kolb et al. (1994) EMBO J. 13,
      3631-3637]. However, no luciferase activity was observed while full-length
      luciferase was attached to the ribosome as a peptidyl-tRNA, probably because the
      C-terminal portion of the enzyme is masked by the ribosome and/or ribosome
      associated proteins. Here we have demonstrated that the ribosome-bound enzyme
      acquires the enzymatic activity when its C-terminus is extended by at least 26
      additional amino acid residues. The results demonstrate that the acquisition of
      the final native conformation by a nascent protein does not need the release of
      the protein from the ribosome.

PMID- 8549827
TI  - Expression and folding of an interleukin-2-proinsulin fusion protein and its
      conversion into insulin by a single step enzymatic removal of the C-peptide and
      the N-terminal fused sequence.
AB  - We report the expression in E. coli of a proinsulin fusion protein carrying a
      modified interleukin-2 N-terminal peptide linked to the N-terminus of proinsulin
      by a lysine residue. The key aspects investigated were: (a) the expression of the
      fused IL2-PI gene, (b) the folding efficiency of the insulin precursor when still
      carrying the N-fused peptide and (c) the selectivity of the enzymatic cleavage
      reaction with trypsin in order to remove simultaneously the C-peptide and the N
      terminal extension. It was found that this construction expresses the chimeric
      proinsulin at high level (20%) as inclusion bodies; the fused protein was
      refolded at 100-200 micrograms/ml to yield about 80% of correctly folded
      proinsulin and then it was converted into insulin by prolonged reaction (5 h)
      with trypsin and carboxypeptidase B at a low enzyme/substrate rate (1:600). This
      approach is based on a single enzymatic reaction for the removal of both the N
      terminal fused peptide and the C-peptide and avoids the use of toxic cyanogen
      bromide.

PMID- 8549828
TI  - The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated
      prior to endocytosis and degradation in the vacuole.
AB  - We have recently demonstrated that the Pdr5 ATP binding cassette multidrug
      transporter is a short-lived protein, whose biogenesis involves cell surface
      targeting followed by endocytosis and delivery to the vacuole for proteolytic
      turnover [Egner, R., Mahe, Y., Pandjaitan, R., and Kuchler, K. (1995) Mol. Cell.
      Biol. 15, 5879-5887]. Using c-myc epitope-tagged ubiquitin, we now have shown
      that Pdr5 is a ubiquitinated plasma membrane protein in vivo. Ubiquitination of
      Pdr5 was detected in both wild type and conditional end mutants defective in
      endocytic vesicle formation. Likewise, the Ste6 a-factor pheromone transporter,
      which represents another short-lived ABC transporter whose turnover requires
      vacuolar proteolysis, was also found to be ubiquitinated, and ubiquitin-modified
      Ste6 massively accumulated in end4 mutants at the restrictive temperature. By
      contrast, the plasma membrane ATPase Pma1, a long-lived and metabolically very
      stable protein, was found not to be ubiquitinated. Our results imply a novel
      function for ubiquitin in protein trafficking and suggest that ubiquitination of
      certain short-lived plasma membrane proteins may trigger their endocytic delivery
      to the vacuole for proteolytic turnover.

PMID- 8549829
TI  - Modification of the targeting presequence of the bovine cytochrome P-450scc
      precursor lifting tissue-specific restrictions on its mitochondrial import.
AB  - It has been found that a recombinant cytochrome P-450scc precursor supplemented
      with an extra MRGSH6GIR sequence at the NH2-terminus (6His-pP450scc) is imported
      into isolated rat liver and heart mitochondria as well as into yeast
      mitochondria. The import is coupled with proteolytic processing of the precursor
      resulting in the mature size form of cytochrome P-450scc. Modification of the
      targeting presequence responsible for its increased positive charge is supposed
      to lift the previously suggested tissue-specific restrictions on the pP450scc
      import into mitochondria.

PMID- 8549831
TI  - The serum albumin-binding domain of streptococcal protein G is a three-helical
      bundle: a heteronuclear NMR study.
AB  - Streptococcal protein G (SPG) is a cell surface receptor protein with a multiple
      domain structure containing tandem repeats of serum albumin-binding domains (ABD)
      and immunoglobulin-binding domains (IgBD). In this paper, we have analysed the
      fold of ABD. Far-UV circular dichroism analysis of ABD indicates high helical
      content (56%). Based on an analysis of nuclear magnetic resonance 13C secondary
      chemical shifts, sequential and short-range NOEs, and a few key nuclear
      Overhauser effects, we conclude that the ABD is a three-helix bundle. The
      structure of the ABD is, thus, quite different from the IgBD of protein G
      [Gronenborn, A.M. et al. (1991) Science 253, 657-661]. This strongly suggests
      that the ABD and the IgBD of SPG have evolved independently from each other.
      However, the fold of ABD is similar to that of the IgBD of staphylococcal protein
      A, possibly indicating a common evolutionary ancestor, despite the lack of
      sequence homology.

PMID- 8549830
TI  - Schizosaccharomyces pombe possesses an unusual and a conventional hexokinase:
      biochemical and molecular characterization of both hexokinases.
AB  - Two hexokinases were characterized in Schizosaccharomyces pombe: hexokinase 1,
      with a low phosphorylation coefficient on glucose (Km 8.5 mM) and hexokinase 2, a
      kinetically conventional hexokinase. Genes hxk1+ and hxk2+ encoding these enzymes
      were cloned and sequenced. Disruption of hxk1+ had no effect on growth but
      disruption of hxk2+ doubled the generation time in glucose. Spores carrying the
      double disruption hxk1+ hxk2+ did not grow on glucose or fructose after one week.
      Expression of hxk1+ increased strongly during growth in fructose or glycerol.
      Expression of hxk2+ was highest during growth in glycerol. A NADP-dependent
      glucose dehydrogenase was detected, but not a glucokinase.

PMID- 8549832
TI  - Molecular characterization of a cDNA encoding functional human deoxyhypusine
      synthase and chromosomal mapping of the corresponding gene locus.
AB  - Deoxyhypusine synthase is essentially required for the post-translational
      formation of hypusine, a modification of a specific lysine residue in eukaryotic
      initiation factor 5A, which appears to be pivotal for cell proliferation. From a
      human peripheral blood mononuclear cells cDNA library we isolated two independent
      sequences encoding biologically active deoxyhypusine synthase. DNA sequence
      analysis revealed a 369 amino acid protein with a molecular mass of 41.055 kDa.
      This recombinant deoxyhypusine synthase showed significant catalytic activity in
      synthesis of deoxyhypusine after in vitro transcription and translation as well
      as upon expression in Escherichia coli. Using a panel of somatic rodent-human
      cell hybrids we localized the deoxyhypusine synthase gene to human chromosome 19.

PMID- 8549833
TI  - Immunochemical detection of ADP-ribosylating enzymes in the archaeon Sulfolobus
      solfataricus.
AB  - Polyclonal antibodies raised against eukaryotic mono-(ADPribose)transferase and
      poly(ADPribose)polymerase were used to test the presence of antigenic
      determinants in a crude extract of Sulfolobus solfataricus, a thermophilic
      archaeon. Samples from eukaryotic (bull testis) and bacterial (E. coli) sources
      were analysed for comparison. All tested antibodies reacted with the sulfolobal
      sample with a specificity comparable to that of the eukaryotic preparation, as
      revealed by ELISA test, activity assays in the presence of antibodies and
      immunoblot experiments. After electrophoresis and western blot of sulfolobal
      proteins, a band at a mass around 50 kDa was detected by immunostaining.

PMID- 8549834
TI  - Halofantrine in the treatment of falciparum malaria.
AB  - 50 patients (45 males + 5 females) suffering from acute uncomplicated attack of
      Plasmodium falciparum (Pf) malaria were treated with 1500 mg of halofantrine
      divided in three doses of 500 mg each given at an interval of 6 h. Results showed
      there were no primary treatment failures. Average Parasite Clearance Time (av.
      PCT) was 51.12 h and average Fever Clearance Time (av. FCT) was 31.25 h. Adverse
      Drug Reactions (ADR) were mild and self limiting. We conclude that halofantrine
      is a quite safe and effective new antimalarial agent in the treatment of Pf
      malaria cases.

PMID- 8549835
TI  - Larvicidal activity of a few plant extracts against Culex quinquefasciatus and
      Anopheles stephensi.
AB  - Larvicidal activity of partially purified extracts of leaves of Vitex negundo,
      Nerium oleander and seeds of Syzygium jambolanum on different instars of Culex
      quinquefasciatus and Anopheles stephensi was estimated. Petroleum ether (PE):
      Ethyl acetate (EA) 3:1 fraction of V. negundo, 1:1 fractions of N. oleander and
      S. jambolanum inflicted considerable larval mortality and interfered with pupal
      adult metamorphosis. At very low concentration the active fractions of these
      plant extracts extended the duration of the various larval instars and of
      pupation. In general, I and II instar larvae were more susceptible to the active
      fractions. Species and stage specific differences in the susceptibility of the
      mosquitoes to the active fractions of the plant extracts were observed.

PMID- 8549836
TI  - Indoor resting anophelines of north Bengal.
AB  - A systematic survey was carried out between April 1993 and March 1994 to study
      the distribution and prevalence of anopheline mosquito species in two malaria
      prone areas situated in the foothills of Darjeeling district. Ten different
      species of Anopheles viz. An. aconitus, An. annularis, An. barbirostris, An.
      culicifacies, An. fluviatilis, An. hyrcanus group, An. maculatus, An. subpictus,
      An. vagus and An. varuna were collected. Per man hour density of mosquitoes
      collected was 4.5 and the most prevalent species was An. vagus, comprising 63% of
      the total catch. An. fluviatilis, an efficient vector of malaria in the foothill
      regions of India, was reported for the first time from this area. However, the
      classical vector of this region viz. An. minimus was altogether absent during the
      course of the present survey. All the ten species were found in cowsheds while,
      human habitation harboured higher population density (56.5%) of the total catch.

PMID- 8549837
TI  - Naturally acquired concomitant infections of bancroftian filariasis and human
      plasmodia in Orissa.
AB  - Blood smears collected from fever cases for detection of malaria parasites during
      daytime showed concomitant infections of Wuchereria bancrofti from 1989 to 1991
      in Bisra PHC of district Sundargarh, Orissa. Of the total 51,448 blood smears
      examined, 18,444 (35.84%) were positive for malaria parasites which comprised
      3401 (18.44%) Plasmodium vivax, 14,524 (78.75%) P. falciparum, 156 (0.84%) P.
      malariae and 363 (1.97%) mixed plasmodial infections. Only 240 (0.46%) cases were
      positive for W. bancrofti, of which 160 (66.67%) were frank microfilariae (mf)
      cases, while 80 (33.33%) showed concomitant infections with malaria parasites.
      Filariasis was less prevalent in lower age-groups. Malaria incidence in people
      below thirty years was higher compared to older people, on the contrary, mf
      incidence was more in people above 15 yrs or more age. Microfilariae density was
      within 1-7 parasites per 10 microliters blood. About 90% mf cases were within the
      range of 1-4 per 10 microliters blood. Mean malaria parasitaemia in concomitant
      infection cases was 9574 per microliters blood (median 5955; range 35 to 49,500).
      Presence of diurnal microfilaraemia needs further investigation.

PMID- 8549838
TI  - Studies on clasper movement of Anopheles species.

PMID- 8549839
TI  - Distribution of indoor-resting Anopheles fluviatilis in human dwellings and its
      implication on indoor residual spray.

PMID- 8549841
TI  - Nutrition in pregnancy. Proceedings of an international workshop. Eindhoven, The
      Netherlands, 25 November 1994.

PMID- 8549840
TI  - Prevalence of malaria among pregnant and non-pregnant women of district Jabalpur,
      Madhya Pradesh.
AB  - In the study period of two years 145 pregnant and 79 non-pregnant women with
      malarial infection were recorded. Plasmodium falciparum was the most prevalent
      species accounting for 72% of the total malaria infection in pregnant women
      while, in non-pregnant women it accounted for 58%. Results were analysed
      according to the species to which the parasite belonged, period of gestation and
      parity. While cerebral malaria, abortions, intrauterine foetal death, maternal
      anaemia were common in pregnant patients, only one neonatal death was recorded.
      Malaria parasites were not found in infants born to mothers with very heavy
      parasitaemia at the time of delivery. Even though pregnant women of all age
      groups and parity remain highly susceptible to malaria throughout pregnancy and
      puerperium from this area, some striking differences like malaria infection more
      prevalent in primigravidas than multigravidas and in second trimester than in
      third trimester were noticed in comparison to northern India. Results emphasize
      the need to target malaria control for this group of women. Failure to clear
      parasitaemia after chloroquine administration in P. falciparum was common in both
      pregnant and non-pregnant women. This is an area, where there is a great need to
      introduce effective malaria interventions. As chloroquine resistant parasites
      spread a better understanding of the problem is needed leading to a few
      chemotherapeutic options for pregnant women.

PMID- 8549842
TI  - Maternal nutrition in relation to fetal and placental growth.
AB  - Babies who are small or disproportionate at birth, or who have altered placental
      growth are now known to be at an increased risk of developing coronary heart
      disease, hypertension and diabetes during adult life. This has led to the
      suggestion that these diseases are 'programmed' by an inadequate supply of
      nutrients to the developing fetus. The phenomenon of 'programming', whereby
      undernutrition in early life permanently changes body structure and function, is
      well documented in animals. As yet, relatively little is known about the maternal
      influences that alter fetal and placental growth, and underlie the programming of
      adult cardiovascular disease during fetal development. There are, however,
      interesting indications that maternal nutrition may be important.

PMID- 8549843
TI  - Timing of prenatal starvation in women and birth weight in their first and second
      born offspring: the Dutch Famine Birth Cohort study.
AB  - OBJECTIVES: To examine the long-term effects of severe in utero maternal
      undernutrition on offspring birth weight. STUDY DESIGN: Birth weights were
      analyzed of 575 first born and 454 second born offspring of 683 women born in
      Amsterdam, the Netherlands, at the time of a severe famine at the end of World
      War II. In utero maternal undernutrition was defined separately for each
      pregnancy trimester by an average daily nutrition ration (supplied to the
      grandmother) of less than 1000 calories in that trimester of pregnancy. RESULTS:
      Compared to controls, birth weights of first born infants of women prenatally
      exposed in the first trimester of pregnancy were 73 g heavier (95% CI: -64, 210),
      and birth weights of second born infants were 96 g lighter (95% CI: -249, 58).
      Birth weights of infants of women exposed in the second or third trimester were
      much closer to controls. CONCLUSIONS: A substantial (200 g or more) impact of
      severe in utero maternal undernutrition on OBW can be ruled out. There may,
      however, be parity specific, moderate (50-100 g) effects of maternal
      undernutrition early in pregnancy on OBW. This suggestion requires confirmation
      in other populations.

PMID- 8549844
TI  - Early human nutrition.
AB  - The Human yolk sac has long been considered a vestigial organ, an evolutionary
      remnant. In the last decade, however, it has been discovered that the human yolk
      sac plays an active and crucial role during organogenesis. Due to an absent
      maternal intervillous circulation during the first 12 weeks of pregnancy, the
      concept of transport of nutrients and oxygen to the embryo must be thoroughly
      reconsidered. Here the yolk sac plays an essential role by its active and passive
      transport to the embryo, and by its production of necessary substances. Animal
      experiments have demonstrated that hyperglycaemia has an initial deleterious
      effect on yolk sac structure, which then results in embryopathy. Study of the
      yolk sac by means of ultrasound has not become an important diagnostic method
      yet. On the basis of clinical studies and animal experiments, however, it may be
      expected that this organ plays a crucial role in the development of spontaneous
      abortion and structural congenital defects.

PMID- 8549845
TI  - Changes of some vitamin levels during and after normal pregnancy.
AB  - Most vitamin status parameters change significantly during pregnancy. A number of
      factors have been associated with this hypovitaminaemia of pregnancy. From our
      data, it was concluded that the initial value of a vitamin status parameter was
      by far the main determinant of the changes of vitamin levels during pregnancy:
      the higher the value, the steeper the decrease. Some hormonal variables were
      associated with these changes as well. This is highly suggestive of a resetting
      of vitamin homeostasis in blood, with a retention of vitamins in maternal
      tissues. The postpartum changes of vitamin levels provide insight into the 'net
      cost' of vitamins during pregnancy. Most serum blood levels of vitamins
      normalized shortly after delivery. Serum vitamin B6 levels increased slowly with
      25% below the acceptable range at 6 months postpartum. However, the GGOT
      stimulation ratio, indicative for vitamin B6 cellular content, was completely
      normal at the time. Serum folacin was the only exception, with 45% serum levels
      in the marginal or deficient range; 20% of this group had deficient or marginal
      red cell folacin levels as well. This indicates that the 'net cost' of folacin
      during pregnancy is considerable, and repletion of folacin stores takes more than
      6 months.

PMID- 8549846
TI  - Folate metabolism and neural tube defects: a review.
AB  - The importance of folate in normal fetal development and wellbeing has been
      recognized only during the past three decades and knowledge concerned is still
      far from complete. In man, folate acts as a substrate in the transfer of one
      carbon moieties and thereby, plays an essential role in the synthesis of several
      amino acids such as methionine and nucleic acids. Consequently, folate
      requirements are related to the amount of tissue growth. Epidemiological,
      clinical and teratological research showed that this B-vitamin is particularly
      involved in the prevention and pathogenesis of neural tube defects. Therefore, in
      this review the metabolism of folate has been outlined. Furthermore, the
      characteristics of the various genically determined folate 'deficiencies' as well
      as a possible biochemical explanation of the relationship between folate and
      neural tube defects are being discussed. Finally, the new recommendations
      launched in November 1993 by the Dutch Health Council as well as the Food and
      Nutrition Council with regard to folate supplementation in the prevention of
      neural tube defects are presented.

PMID- 8549847
TI  - Periconceptional vitamin supplementation to prevent neural tube defects: how can
      we do it?
AB  - The discovery that folic acid can reduce neural tube defect rates offers a great
      opportunity for primary prevention. Unfortunately, women must receive the folic
      acid before or immediately after conception, before many know that they are
      pregnant. Thus, we are faced with a difficult choice: (1) ask all women at risk
      of getting pregnant to take supplements, or (2) fortify the food supply to ensure
      that all women at risk receive additional folic acid. Neither approach is ideal.
      Many women will not take vitamin supplements. Fortification at sufficiently high
      levels to provide all women with 400 micrograms of folic acid will expose other
      segments of the population to unacceptably high levels. Because many women of
      child-bearing age are unaware of the benefits of folic acid, a vigorous education
      campaign should begin immediately to encourage women at risk to take supplements.
      Adding 70 micrograms of folic acid per 100 g of grain could be justified easily
      because this amount is removed from grain in processing. If it is technically
      feasible, adding up to 140 micrograms is likely to be safe, and could prevent
      more NTDs. A major educational campaign and modest fortification of grain with
      folic acid may be the best practical solution.

PMID- 8549848
TI  - Essential fatty acids in pregnancy and early human development.
AB  - Essential fatty acids (EFA) are vitally important structural elements of cell
      membranes and, therefore, instrumental in the formation of new tissues. The
      primary EFA cannot be synthesized by man and, consequently, humans depend on
      dietary sources for an adequate EFA supply. Fetal development is associated with
      a high EFA requirement, and for its EFA supply, the developing fetus depends on
      the availability of maternal EFA. At delivery, a strong correlation is observed
      between the relative amounts of the various EFA in maternal and umbilical plasma
      phospholipids (PL), which underlines this fetal dependence. In a longitudinal
      study, we observed that, in women, the EFA status progressively decreases during
      pregnancy. This particularly holds for cervonic acid (CA, 22:6n-3, also named
      Docosahexaenoic acid, DHA), the major structural and functional EFA in the CNS.
      In addition, evidence was obtained for CA mobilization from maternal stores
      during pregnancy. Furthermore, the maternal CA status appeared significantly
      higher in primigravida than in multigravida. This was associated with a tendency
      for the first child of a given woman to have a higher CA status than her
      following children. This suggests that maternal CA mobilization during pregnancy
      occurs from a pool that is not easily replenished after pregnancy. The fetal CA
      status of premature infants is positively related to head circumference, birth
      weight and birth length. This may imply that increasing the fetal CA status could
      promote fetal growth and, thereby, improve the general prognosis of prematures.
      In conclusion, our data suggest that increasing the maternal EFA intake during
      pregnancy may be beneficial to both mother and child.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8549849
TI  - Low sodium diet in pregnancy: effects on maternal nutritional status.
AB  - In the present study, besides the effect on blood pressure, the effects of a low
      sodium diet in pregnancy on maternal energy and nutrient intake, calcium
      metabolism, zinc and magnesium status, weight gain and body fat storage were
      investigated. No effect of the low sodium diet in pregnancy on the course of
      blood pressure and the incidence of hypertensive disorders was observed. The
      reduction in sodium intake also caused a significant reduction in the intake of
      energy, protein, carbohydrates, fat, calcium, zinc, magnesium, iron and
      cholesterol. The reduced intake of calcium, zinc and magnesium in the women on
      the low sodium diet did not result in significant changes in circulating total
      calcium, ionized calcium, parathyroid hormone, zinc, alkaline phosphatase or
      magnesium, probably because of homeostatic adaptations by the kidneys. In the
      women on the low sodium diet non-significant reductions in weight gain (1.5 kg)
      and fat mass gain (0.9 kg) over pregnancy were observed. These reductions in
      weight and fat mass gain were more pronounced (3.4 kg (P = 0.003) and 1.3 kg (P =
      0.15), respectively) when only the data of the women with good compliance were
      analyzed. The use of a low sodium diet in pregnancy did not have significant
      effects on infant birth weight, placental weight or other pregnancy outcome
      variables.

PMID- 8549850
TI  - Iron supplementation during pregnancy.
AB  - There is world-wide concern that women of childbearing age cannot meet the
      increased iron needs during pregnancy. In the industrial world however, iron
      supplementation during pregnancy is a controversial issue. On the one hand,
      selective iron supplementation after iron status assessment has been recommended
      because not all women need iron, and compliance is likely to be better when an
      individual's need is recognized. On the other hand, routine iron supplementation
      to all women in the second half of pregnancy has been advocated in order to reach
      all women without the difficulties associated with assessment of iron status.
      Pregnant women could possibly meet their iron needs by increasing iron absorption
      efficiency. Although in that case, dietary counselling may prevent anaemia during
      pregnancy, supplementation with iron will be necessary to cure iron-deficiency
      anaemia.

PMID- 8549851
TI  - Energy requirements of pregnancy for healthy Dutch women.
AB  - Over the past 15 years we have performed several longitudinal studies with
      healthy Dutch women, in which components of an energy balance were measured
      before, during and after pregnancy. The observed small changes in energy intake
      over pregnancy are insufficient to meet the energy costs of pregnancy. This
      suggests that substantial savings were made on energy expenditure. We found no
      evidence for improvement of digestibility, for lower energy costs in ingesting,
      absorbing, transporting and storing nutrients, or for lower energy costs for
      performing fixed-paced physical tasks. So, it appears that our Dutch women cannot
      increase the efficiency of their energy metabolism. However we could clearly
      demonstrate that our women reduced their daily energy expenditure by decreasing
      the amount and pace of physical activity. In summary, our studies suggest there
      is no need for well-nourished western women to increase food intake in pregnancy,
      provided that the mothers reduce their level of physical activity. However, since
      the requirements for specific nutrients are increased in pregnancy, special
      attention should be given to the quality of the diet.

PMID- 8549852
TI  - Nutrition and breast-feeding.
AB  - In the western industrialized world, malnutrition of the lactating mother is not
      a problem any more. However, new problems, the chemical pollutants in breastmilk,
      have given rise to concern. Since the seventies, pollution of breastmilk with
      PCBs and dioxins has taken place. After World War II, more and more PCBs and
      dioxins entered the environment. Because of the low half-life of these chemicals,
      persistence leading to accumulation in animal and human fat has taken place. The
      baby, before birth and when breast-fed, is the highest animal in the food chain,
      consuming the most concentrated amount of PCBs and dioxins in his/her daily fat
      intake. Exposure before and after birth has given rise to subtle abnormalities in
      approximately 10% of the newborns in the Netherlands. These subtle abnormalities
      are a disturbed cognitive development and a delayed motor-development. Severe
      vitamin K deficiency can be caused by these contaminants as well. Because of the
      very threatening situation, a study was performed to look for the possibilities
      of prevention by influencing the diet of the lactating mother. Two diets were
      tested for their ability to reduce concentrations of dioxins in human milk. The
      diets were a low-fat/high-carbohydrate/low-dioxin diet (about 20% of energy
      intake derived from fat) and a high-fat/low-carbohydrate/low-dioxin diet. Despite
      significant influences of these diets on the fatty acid profiles, no significant
      influence on the dioxin concentrations in breast milk could be found. We conclude
      that short-term dietary measures will not reduce dioxin concentrations in human
      milk. A lowering of intake of these chemicals must take place years before the
      mother becomes pregnant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549853
TI  - Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the
      cellular energy circuit.
AB  - Physiologically, a postprandial glucose rise induces metabolic signal sequences
      that use several steps in common in both the pancreas and peripheral tissues but
      result in different events due to specialized tissue functions. Glucose transport
      performed by tissue-specific glucose transporters is, in general, not rate
      limiting. The next step is phosphorylation of glucose by cell-specific
      hexokinases. In the beta-cell, glucokinase (or hexokinase IV) is activated upon
      binding to a pore protein in the outer mitochondrial membrane at contact sites
      between outer and inner membranes. The same mechanism applies for hexokinase II
      in skeletal muscle and adipose tissue. The activation of hexokinases depends on a
      contact site-specific structure of the pore, which is voltage-dependent and
      influenced by the electric potential of the inner mitochondrial membrane.
      Mitochondria lacking a membrane potential because of defects in the respiratory
      chain would thus not be able to increase the glucose-phosphorylating enzyme
      activity over basal state. Binding and activation of hexokinases to mitochondrial
      contact sites lead to an acceleration of the formation of both ADP and glucose-6
      phosphate (G-6-P). ADP directly enters the mitochondrion and stimulates
      mitochondrial oxidative phosphorylation. G-6-P is an important intermediate of
      energy metabolism at the switch position between glycolysis, glycogen synthesis,
      and the pentose-phosphate shunt. Initiated by blood glucose elevation,
      mitochondrial oxidative phosphorylation is accelerated in a concerted action
      coupling glycolysis to mitochondrial metabolism at three different points: first,
      through NADH transfer to the respiratory chain complex I via the malate/aspartate
      shuttle; second, by providing FADH2 to complex II through the glycerol
      phosphate/dihydroxy-acetone-phosphate cycle; and third, by the action of
      hexo(gluco)kinases providing ADP for complex V, the ATP synthetase. As cytosolic
      and mitochondrial isozymes of creatine kinase (CK) are observed in insulinoma
      cells, the phosphocreatine (CrP) shuttle, working in brain and muscle, may also
      be involved in signaling glucose-induced insulin secretion in beta-cells. An
      interplay between the plasma membrane-bound CK and the mitochondrial CK could
      provide a mechanism to increase ATP locally at the KATP channels, coordinated to
      the activity of mitochondrial CrP production. Closure of the KATP channels by ATP
      would lead to an increase of cytosolic and, even more, mitochondrial calcium and
      finally to insulin secretion. Thus in beta-cells, glucose, via bound glucokinase,
      stimulates mitochondrial CrP synthesis. The same signaling sequence is used in
      the opposite direction in muscle during exercise when high ATP turnover increases
      the creatine level that stimulates mitochondrial ATP synthesis and glucose
      phosphorylation via hexokinase. Furthermore, this cytosolic/mitochondrial cross
      talk is also involved in activation of muscle glycogen synthesis by glucose. The
      activity of mitochondrially bound hexokinase provides G-6-P and stimulates UTP
      production through mitochondrial nucleoside diphosphate kinase.
      Pathophysiologically, there are at least two genetically different forms of
      diabetes linked to energy metabolism: the first example is one form of maturity
      onset diabetes of the young (MODY2), an autosomal dominant disorder caused by
      point mutations of the glucokinase gene; the second example is several forms of
      mitochondrial diabetes caused by point and length mutations of the mitochondrial
      DNA (mtDNA) that encodes several subunits of the respiratory chain complexes.
      Because the mtDNA is vulnerable and accumulates point and length mutations during
      aging, it is likely to contribute to the manifestation of some forms of
      NIDDM.(ABSTRACT TRUNCATED)

PMID- 8549854
TI  - A subtractive cloning approach to the identification of mRNAs specifically
      expressed in pancreatic beta-cells.
AB  - A polymerase chain reaction-based subtractive hybridization procedure was applied
      to cDNAs prepared from mouse insulinoma (beta TC3) and glucagonoma (alpha TC2)
      cell lines to construct a library of cDNAs that are highly expressed in
      pancreatic beta-cells. An analysis of 555 randomly chosen clones in the library
      showed that 80 were derived from abundant mRNAs and were accounted for by 29
      distinct sequences. Of these, 17 were identical or homologous to known mammalian
      cDNAs or expressed sequence tags. Genes known to be highly expressed in beta
      cells were represented at a high frequency, namely insulin (15 of 80 clones),
      islet amyloid polypeptide (8 of 80 clones), proinsulin convertase 1 (6 of 80
      clones), and neuropeptide Y (2 of 80 clones). Many of the novel cDNA sequences
      that were highly represented in the library showed a relative specificity to beta
      cells compared with other tissues, including glucagonoma, liver, kidney, brain,
      3T3 fibroblasts, and AtT20 corticotrophs, and warrant further investigation. When
      combined with functional or immunological screening procedures, the approach will
      be useful for the isolation of beta-cell-specific molecules for immunological and
      genetic investigations of beta-cell function and pathology.

PMID- 8549855
TI  - Hepatic insulin resistance after pancreas transplantation in type I diabetes.
AB  - Hyperinsulinemia and peripheral insulin resistance caused by systemic insulin
      delivery and prednisone therapy are recognized consequences of pancreas
      transplantation. However, there is little information about insulin action on the
      liver. To investigate hepatic insulin sensitivity in recipients of pancreas
      transplants, we devised a staged euglycemic hyperinsulinemic clamp to measure
      hepatic glucose production (HGP) in 10 type I diabetic pancreas transplant
      recipients, 10 pair-matched healthy control subjects, and 6 nondiabetic kidney
      transplant recipients. Clamps were performed in two sequential stages. In stage
      1, a 2-h low-dose insulin infusion (0.4 mU.kg-1.min-1) was used to partially
      suppress HGP. In stage 2, insulin-mediated suppression of HGP was challenged by a
      1.5-h glucagon infusion (0.8 ng.kg-1.min-1), while continuing the
      hyperinsulinemic euglycemic-clamp conditions. During both stages, somatostatin
      (250 micrograms/h) was infused to suppress endogenous insulin secretion. All
      subjects underwent stage 1, and all except one pancreas recipient and a
      respective matched healthy control subject completed stage 2. Fasting HGP was
      greater in pancreas recipients than in healthy control subjects (15.1 +/- 0.7 vs.
      12.0 +/- 0.4 mumol.l-1.kg-1.min-1, P < 0.005) but similar in healthy control
      subjects and in kidney recipients. During stage 2, both total (706 +/- 28 vs. 469
      +/- 31 mumol.l-1.kg-1, P < 0.005) and incremental (62 +/- 20 vs. -21 +/- 16
      mumol.l-1.kg-1, P < 0.005) HGP responses to glucagon infusion were significantly
      greater in pancreas recipients than in healthy control subjects. Changes in HGP
      in kidney recipients during stage 2 were not significantly different from those
      in healthy control subjects. In conclusion, fasting HGP is increased in pancreas
      transplant recipients. Furthermore, recipients have hepatic insulin resistance as
      demonstrated by an enhanced stimulatory effect of glucagon on HGP during insulin
      mediated HGP suppression. Because the magnitude of hepatic insulin resistance was
      a significant (P < 0.01) predictor of HbA1c level, we suggest that variable
      hepatic insulin resistance may be responsible for some of the variance observed
      in glycemic levels after successful pancreas transplantation.

PMID- 8549856
TI  - Selective damage to sensorimotor perivascular nerves in the mesenteric vessels of
      diabetic rats.
AB  - The perivascular innervation of the superior mesenteric artery and vein was
      examined using immunohistochemical and immunoassay techniques in rats 8 weeks
      after induction of diabetes with streptozotocin (STZ). Increased density of
      innervation and fluorescence intensity was noted for substance P- and calcitonin
      gene-related peptide-immunoreactive nerves in the diabetic vessels. A slight
      increase in the density of vasoactive intestinal polypeptide-immunoreactive nerve
      fibers innervating the mesenteric artery was also noted. However, there was no
      change in the density of neuropeptide Y- and dopamine beta-hydroxylase
      immunoreactive nerve fibers, although the fluorescence intensity of neuropeptide
      Y-immunoreactive nerve fibers was reduced in diabetic rat vessels. Immunoassays
      showed that the levels of substance P- and calcitonin gene-related peptide were
      increased > 10-fold in the diabetic mesenteric vein, while levels of neuropeptide
      Y and vasoactive intestinal polypeptide were unchanged. In summary, there is a
      marked increase in nerve fibers containing sensory neuropeptides in mesenteric
      vessels of STZ-induced diabetic rats, which, in view of the reported impaired
      sensorimotor function in these vessels, is likely to reflect a neuropathic
      change.

PMID- 8549857
TI  - Induction of allogeneic islet survival by intrahepatic islet preimmunization and
      transient immunosuppression.
AB  - Induction of tolerance to fully major histocompatibility complex (MHC)-mismatched
      rat islet allografts implanted at two different islet transplant sites (liver and
      kidney capsule [KC]) was examined. Streptozotocin-induced diabetic Lewis (RT1(1))
      rats remained hyperglycemic (> 200 mg/dl) after intrahepatic preimmunization by
      injection of 200 low-temperature cultured (24 degrees C for 7 days) Wistar-Furth
      (WF, RT1u) rat islets into the portal vein with one injection (1 ml) of rat
      antilymphocyte serum intraperitoneally. Three weeks later, 1,200 WF islets that
      had been cultured to remove passenger lymphoid cells were transplanted into the
      liver via the portal vein or under the KC. The intrahepatic transplants survived
      60.2 +/- 11.9 days, and all six of the KC transplants maintained normoglycemia
      for > 100 days after the preimmunization regimen. In contrast, survival of fresh
      islet transplants was not significantly improved by this preimmunization protocol
      at either transplantation site. This study demonstrates that indefinite islet
      allograft survival can be achieved across a full MHC mismatch by intrahepatic
      preimmunization with a small number of cultured donor islets and a brief period
      of immunosuppression followed by transplantation of low-temperature cultured
      donor islets.

PMID- 8549858
TI  - The roles of catecholamines in glucoregulation in intense exercise as defined by
      the islet cell clamp technique.
AB  - Exercise at > 85% VO2max causes the greatest known physiological increases in
      glucose production rates (Ra). To define the relative roles of catecholamine
      versus glucagon/insulin responses in stimulating Ra, normal subjects in the
      postabsorptive state exercised at 87 +/- 2% VO2max during an islet cell clamp
      (IC): intravenous octreotide (somatostatin analog), 30 ng.kg-1.min-1; glucagon,
      0.8 ng.kg-1.min-1; growth hormone, 10 ng.kg-1.min-1; and insulin adjusted to
      achieve euglycemia, then constant 56 +/- 7 min before exercise. Seven control
      subjects exercised without an IC. In four subjects (IC-1) with hormone infusions
      held constant during exercise, plasma insulin rose 76% and glucagon 35%, perhaps
      because of altered hemodynamics. In seven subjects (IC-2), hormone infusions were
      decreased stepwise during exercise and returned stepwise to initial rates during
      early recovery. Ra increased sixfold in control and both IC groups. Plasma
      norepinephrine and epinephrine likewise increased > 12-fold with no differences
      among groups; both catecholamines correlated closely with Ra. Because mixed
      venous blood plasma insulin declined and glucagon did not change in control
      subjects, the glucagon-to-insulin ratio increased from 0.20 to 0.26 (P = 0.02).
      In IC subjects, plasma insulin increased and glucagon was either constant (IC-2)
      or increased less than insulin, resulting in nonsignificant declines in the
      immunoreactive glucose-to-immunoreactive insulin ratio. Although a rise in
      insulin would have been expected to attenuate the Ra increment, this effect was
      overridden. The strong correlations of Ra with catecholamines and the similar Ra
      responses despite divergent glucagon-to-insulin responses are consistent with the
      primacy of catecholamines in regulation of Ra in intense exercise.

PMID- 8549859
TI  - Identification of trinucleotide repeat-containing genes in human pancreatic
      islets.
AB  - In the search for diabetes genes, the combined approaches of positional cloning
      with random markers and subsequent evaluation of candidate genes mapping to areas
      of interest will be increasingly used. For islet candidate genes of unknown
      function, expressed trinucleotide (triplet) repeats represent a unique subset. It
      is unlikely that abnormal expansion of expressed islet triplet repeats would be a
      major cause of diabetes, yet the triplet repeats are frequently polymorphic and
      can thus be used to map the genes in the human genome. In this study, a human
      islet cDNA library was screened with (CGG)7 and (CAG)7, and 23 triplet repeats
      were isolated. Sequencing revealed four known and six novel islet genes
      containing 4-15 triplet repeats. The four known cDNAs included ferritin, the
      major iron-binding protein in cells; HSGSA2R, a full-length clone of the alpha
      subunit of the G-regulatory protein; HUMSATB1A, a DNA-binding protein expressed
      predominantly in thymus; and HUMPPA-PRO, a ribosomal protein. The triplet repeats
      in ferritin and HUMPPAPRO were found to be monomorphic. Characterization of the
      six unique novel expressed islet triplet cDNAs revealed that they were 0.6-1.5 kb
      in size, contained 4-15 triplet repeats, and were expressed in islets and all
      other tissues examined. Four of the novel clones, CGG-isl 10, CGG-isl 11, CAG-isl
      6, and CAG-isl 7, were mapped to human chromosomes 19, 16, 12, and 3,
      respectively, via somatic cell hybrids. One islet cDNA, CAG-isl 7, contained a
      repeat that was highly polymorphic, with 14 alleles (4-18 triplets) in African
      Americans (heterozygosity = 0.86) and 6 alleles (heterozygosity = 0.77) in
      whites. Northern analysis indicated that the mRNA was abundant in pancreatic
      islets. A putative full-length clone contained an open reading frame encoding 213
      amino acids with a variable number of alanines (4-18) within the COOH-terminal.
      The gene was uniquely mapped with odds > 1,000:1 on chromosome 3p in Centre
      d'Etude du Polymorphisme Humain pedigrees. There were no differences in CAG-isl 7
      allele frequencies between African-American patients with NIDDM (n = 108) and
      control subjects (n = 116), nor was expansion above 18 repeats noted. Linkage
      analysis in 14 nonglucokinase maturity-onset diabetes of the young pedigrees
      showed a cumulative logarithm of odds score of -33.19 at theta = 0.00. Abnormal
      expansion was not observed in 20 IDDM patients with one NIDDM parent. While these
      data suggest no major role for CAG-isl 7 in diabetes, at least four of the six
      novel islet triplet genes are coexpressed in pancreatic islets and neural tissue,
      and these genes can now be considered as candidates for diabetes and/or
      neuropsychiatric diseases.

PMID- 8549860
TI  - Immune response to heat-shock protein correlates with induction of insulitis in I
      E alpha d transgenic NOD mice.
AB  - To evaluate the correlation between heat-shock protein (HSP) and insulitis, we
      compared lymphocyte proliferative response to Mycobacterium leprae HSP65 of NOD
      mice with that of I-E alpha d transgenic NOD (I-E+NOD) mice, which show no
      insulitis. We found that splenocytes from 15-week-old NOD mice showed a more
      marked proliferative response to HSP than did those from age-matched I-E+NOD mice
      (P < 0.05). We then transferred splenocytes from 12-week-old NOD mice into I
      E+NOD mice to induce insulitis in the recipients and examined antibody levels
      against HSP. By 6 weeks posttransfer, insulitis was successfully transferred to
      four out of five recipients of NOD splenocytes and antibody levels against HSP
      were significantly higher in the NOD splenocyte-transferred group than in
      controls, which showed no insulitis (P < 0.01). These results suggest that immune
      response to HSP correlates with insulitis in NOD mice. Our results support the
      assertion that HSP is a useful antigen for investigating the etiology of IDDM.

PMID- 8549861
TI  - Conjoint IGF-I and insulin infusion shows diverse interactive effects in diabetic
      rats.
AB  - Studies in diabetic rodents and humans provide evidence that IGF-I may alleviate
      the diabetic state and insulin resistance to some degree. To assess the efficacy
      of IGFs as an adjunct treatment with insulin in diabetes, we infused IGF-I or
      des(1-3)IGF-I for 7 days at 0, 10.7, 26.7, and 66.8 nmol/day to streptozotocin
      induced diabetic rats in conjunction with infusions of 0, 2.2, 5.6, or 14
      nmol/day insulin. Both insulin and des(1-3)IGF-I increased body weight gain by 7
      g/day compared with controls (1.2 g/day), but there was no additive effect.
      However, for nitrogen retention, the effects of des(1-3)IGF-I were additive with
      those of 2.2 nmol/day insulin. Des(1-3)IGF-I was two- to threefold more potent
      than IGF-I. At comparable rates of total nitrogen retention, carcass nitrogen
      retention was approximately 35% higher with insulin than with IGF treatment,
      indicating a differential tissue response. IGFs did not alter carcass fat
      content. Des(1-3)IGF-I increased liver glycogen additively with insulin but
      reduced glucosuria only when given with 5.6 nmol insulin per day, indicating the
      possibility of a facilitatory effect, perhaps via increased insulin sensitivity.
      Insulin was 10- to 25-fold more potent in these glucoregulatory actions.
      Differential effects of the hormones were also observed for kidney, liver, and
      thymus weights. We conclude that IGFs and especially the more potent des(1-3)IGF
      I may have a role as an adjunct to insulin therapy in diabetic patients.

PMID- 8549862
TI  - Cellular immune response to cow's milk beta-lactoglobulin in patients with newly
      diagnosed IDDM.
AB  - Elevated levels of antibodies to cow's milk proteins, i.e., beta-lactoglobulin
      (BLG) and bovine serum albumin (BSA), have been associated with IDDM. We observed
      enhanced cellular immune response by a proliferation test of peripheral blood
      mononuclear cells to BLG in 22 of 40 (55%) patients with newly diagnosed IDDM
      compared with 7 of 32 healthy children (22%) (P = 0.004, chi 2 test). The median
      stimulation index to BLG was 3.3 in patients and 1.5 in healthy children (P =
      0.003, Mann-Whitney U test). No difference was found in cellular reactivity to
      other cow's milk proteins, such as BSA or alpha-casein, or to a dietary
      immunogenic protein, ovalbumin. Cellular responsiveness to BLG was not associated
      with HLA-DQB1* risk alleles of IDDM, which suggests that immune response to the
      protein does not only reflect the accumulation of these HLA alleles in the
      patients with IDDM. We suggest that enhanced cellular immune response to dietary
      BLG may reflect a disturbance in the regulation of immune response to oral
      antigens in IDDM. This kind of defect may play a fundamental role in the
      development of beta-cell autoimmunity in IDDM.

PMID- 8549863
TI  - Tumor necrosis factor-alpha and interferon-gamma inhibit insulin secretion and
      cause DNA damage in unweaned-rat islets. Extent of nitric oxide involvement.
AB  - Nitric oxide has been implicated as one possible mediator of interleukin-1 beta
      (IL-1)-induced inhibition of insulin secretion and islet cell damage. The aim of
      this study was to define the effects of tumor necrosis factor-alpha (TNF) and
      interferon-gamma (IFN) on nitric oxide production, insulin secretion, and DNA
      damage in islets from unweaned rats. Treatment of islets with 0.5-500 U/ml of
      either TNF or IFN on their own inhibited glucose-stimulated insulin secretion in
      a dose-dependent manner (minimum effective dose 5 U/ml). In combination, the
      cytokines exerted a pronounced synergistic inhibitory effect on secretion and
      were equipotent at causing a significant and concentration-dependent increase in
      culture medium nitrite levels, islet cyclic GMP formation, and DNA damage. Used
      alone or in combination, TNF and IFN significantly enhanced the activity of
      inducible nitric oxide synthase as determined by measuring the conversion of 14C
      labeled arginine to 14C-labeled citrulline and nitric oxide. Use of arginine-free
      medium, without or with NG-monomethyl-L-arginine, resulted in inhibition of
      nitrite formation by 5-1,000 U/ml IFN+TNF and partial restoration of the insulin
      secretory response to glucose. Treatment of rat islets with increasing doses of
      TNF+IFN (5, 50, and 500 U/ml) resulted in a progressive increase in DNA damage,
      as shown by the comet assay, which detects DNA strand breaks in individual islet
      cells. The DNA damage caused by an intermediate concentration (50 U/ml) of
      TNF+IFN was comparable to that generated by IL-1 when used at 20 U/ml. We
      conclude that TNF and IFN induce nitric oxide formation, which partially inhibits
      glucose-induced insulin secretion and causes significant DNA strand breakage, but
      that as cytokine concentrations increase, non-nitric-oxide-mediated events
      predominate.

PMID- 8549864
TI  - Evidence for an anaplerotic/malonyl-CoA pathway in pancreatic beta-cell nutrient
      signaling.
AB  - A metabolic model of fuel sensing has been proposed in which malonyl-CoA and long
      chain acyl-CoA esters may act as coupling factors in nutrient-induced insulin
      release (Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney J, Corkey BE:
      Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in
      nutrient-induced insulin secretion. J Biol Chem 267:5802-5810, 1992). To gain
      further insight into the control of malonyl-CoA content in islet tissue, we have
      studied the short- and long-term regulation of acetyl-CoA carboxylase (ACC) and
      fatty acid synthase (FAS) in the beta-cell. These enzymes catalyze the formation
      of malonyl-CoA and its usage for de novo fatty acid biogenesis. ACC mRNA,
      protein, and enzymatic activity are present at appreciable levels in rat
      pancreatic islets and clonal beta-cells (HIT cells). Glucose addition to HIT
      cells results in a marked increase in ACC activity that precedes the initiation
      of insulin release. Fasting does not modify the ACC content of islets, whereas it
      markedly downregulates that of lipogenic tissues. This indicates differential
      regulation of the ACC gene in lipogenic tissues and the islets of Langerhans. FAS
      is very poorly expressed in islet tissue, yet ACC is abundant. This demonstrates
      that the primary function of malonyl-CoA in the beta-cells is to regulate fatty
      acid oxidation, not to serve as a substrate for fatty acid biosynthesis. The
      anaplerotic enzyme pyruvate carboxylase, which allows the replenishment of citric
      acid cycle intermediates needed for malonyl-CoA production via citrate, is
      abundant in islet tissue. Glucose causes an elevation in beta (HIT)-cell citrate
      that precedes secretion, and only those nutrients that can elevate citrate induce
      effective insulin release. The results provide new evidence in support of the
      model and explain why malonyl-CoA rises markedly and rapidly in islets upon
      glucose stimulation: 1) glucose elevates citrate, the precursor of malonyl-CoA;
      2) glucose enhances ACC enzymatic activity; and 3) malonyl-CoA is not diverted to
      lipids. The data suggest that ACC is a key enzyme in metabolic signal
      transduction of the beta-cell and provide evidence for the concept that an
      anaplerotic/malonyl-CoA pathway is implicated in insulin secretion.

PMID- 8549865
TI  - Altered GAP-43 immunoreactivity in regenerating sciatic nerve of diabetic rats.
AB  - Experimental diabetes in the rat is associated with impaired axon regeneration.
      Successful regeneration depends on the construction of axonal growth cones and
      establishment of appropriate target connections. The growth-associated protein
      (GAP)-43 is a major component of the axonal growth cone, and its synthesis and
      axonal transport are markedly increased during regeneration. The purpose of this
      study was to determine the effect of experimental diabetes on the synthesis and
      axonal transport of GAP-43 in regenerating sciatic nerves. Rats were rendered
      diabetic with 50 mg/kg streptozotocin i.p. Four weeks later, the rats were
      anesthetized, and one sciatic nerve was crushed to induce regeneration. After 2
      weeks, nerves were ligated, and 6 h later, nerve pieces proximal to the ligature
      and dorsal root ganglia were removed, and proteins were separated by PAGE.
      Western blots of gels were probed with antibody 10E8/E7 against GAP-43. The
      presence of GAP-43 was confirmed by immunohistochemistry of nerve sections.
      Densitometric analysis of the blots showed a 45% reduction in native GAP-43
      immunoreactivity in nerve pieces proximal to the ligature (P < 0.05; n = 7).
      Northern blots of total RNA extracted from pooled dorsal root ganglia were probed
      with a 32P-radiolabeled cDNA probe for GAP-43. There was no significant
      difference in the amount of GAP-43 mRNA between diabetic and nondiabetic rats.
      Immunohistochemistry of sciatic nerve confirmed the reduction in GAP-43
      immunoreactivity. We conclude that a defect in turnover or axonal transport of
      GAP-43 may contribute to the impaired peripheral nerve regeneration in diabetes.

PMID- 8549866
TI  - Immunological and metabolic effects of prophylactic insulin therapy in the NOD
      scid/scid adoptive transfer model of IDDM.
AB  - Prophylactic insulin therapy prevents IDDM in spontaneous animal models of the
      disease and has shown promise in preventing the disease in humans. Although large
      clinical trials have been formed to use this therapy, a comparative analysis of
      the efficiency of different pharmaceutical forms and doses of insulin in
      preventing IDDM has not been performed, and the mechanism underlying the observed
      prevention of disease is unknown. In the NOD-scid/scid adoptive transfer model of
      IDDM (10(7) new-onset NOD splenocytes injected intravenously into 6- to 8-week
      NOD/scid-scid recipients; insulitis develops at 6-9 days post-transfer and 100%
      IDDM by 32 days post-transfer), life-table (log-rank) analyses revealed that IDDM
      can be delayed (compared with insulin-free diluent, once daily, n = 8) with
      equivalent efficiency by prophylactic administration (-9-50 days post-transfer)
      of high (metabolism-altering) doses of short-acting (0.5 U, once daily, regular,
      n = 13) or long-acting (0.5 U, once daily, ultralente, n = 9) insulin as well as
      non-metabolism-altering low-dose insulin (0.02 U, once daily, regular, n = 8).
      Furthermore, IDDM was delayed with somatostatin (0.2 microgram, twice daily, n =
      11), an agent that suppresses endogenous insulin production. No significant
      difference was seen between the preventative effects of these agents. In an
      assessment of when therapies can be initiated and still maintain clinical
      efficiency, only prophylactic somatostatin therapy delayed IDDM (n = 10, P =
      0.02) when initiated at 14 days post-transfer, whereas the short-acting insulin
      regimen did not retard the onset of IDDM (n = 8, P = 0.25) compared with diluent
      treated controls. The 24-h urinary C-peptide levels were significantly reduced
      with short-acting (-56%, P = 0.01) and long-acting (-67%, P = 0.02) insulin
      products and somatostatin (-59%, P = 0.02) compared with diluent-treated
      controls. These results indicate that both immunological and metabolic (i.e.,
      beta-cell rest) factors may contribute to the beneficial effects of prophylactic
      insulin therapy.

PMID- 8549867
TI  - The effect of hyperglycemia on nerve conduction and structure is age dependent.
AB  - The nerve conduction velocity (NCV) of nondiabetic male Wistar rats continues to
      increase until approximately 26 weeks of age. Rats made hyperglycemic at 6 weeks
      of age manifest reduced NCV by 10 weeks of age and show morphological differences
      in the sciatic tibial nerve after 5 months of hyperglycemia when compared with
      age-matched controls. Fiber diameter, myelin width, and the number of large
      myelinated fibers were decreased in the tibial nerves of the hyperglycemic
      animals. Rats made hyperglycemic at 26 weeks of age had elevated glycosylated
      hemoglobin and sciatic nerve sorbitol levels but maintained normal NCVs and had
      little change in morphology after 7 months of hyperglycemia. Thus, animals with
      maturing peripheral nerve structure and function exposed to chronic hyperglycemia
      manifest greater pathological alterations than those that occur when more matured
      nerves are exposed to similarly elevated glucose concentrations for an even
      greater duration. We suggest that immature animal models commonly used to study
      diabetic peripheral neuropathy may not be appropriate for understanding a process
      that commonly develops in humans who become hyperglycemic after maturation of the
      peripheral nerves.

PMID- 8549868
TI  - Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM
      patients.
AB  - Contrasting information has been reported concerning the course of renal function
      in NIDDM with hypertension alone or in association with renal damage. The aim of
      the present study was to elucidate the course of the glomerular filtration rate
      (GFR) in hypertensive NIDDM patients during antihypertensive therapy.
      Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace,
      Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer,
      Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's
      clinic of the internal medicine departments of the University of Padova and
      Sassari, 44 participated in the present study. Of these patients, 26 were
      normoalbuminuric and 18 microalbuminuric. They were randomly treated with either
      cilazapril or amlodipine. The target of antihypertensive treatment was a value <
      140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP).
      Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and
      200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at
      baseline and every 6-12 months during a 3-year follow-up interval. A significant
      decrease was observed in the values of GFR, AER, and systolic and diastolic BP in
      normoalbuminuric and microalbuminuric patients during antihypertensive therapy.
      The GFR fall in the overall population of NIDDM patients was significantly and
      inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r
      = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR
      decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66
      ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min
      1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per
      year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95%
      CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year
      (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered
      AER to a similar extent in normoalbuminuric and microalbuminuric patients. No
      significant changes were observed concerning other clinical and biochemical
      features between the two antihypertensive therapies and particularly HbA1c, BMI,
      triglycerides, and cholesterol plasma values. These results support the tenet
      that arterial hypertension plays a pivotal role in contributing to renal damage
      in NIDDM, even when AER is normal. However, the degree of BP control, with both
      cilazapril and amlodipine, can successfully delay the slope of GFR decline in
      hypertensive NIDDM patients with or without incipient nephropathy.

PMID- 8549869
TI  - Banting Lecture 1995. A lesson in metabolic regulation inspired by the
      glucokinase glucose sensor paradigm.
AB  - Special features of glucose metabolism in pancreatic beta-cells are central to an
      understanding of the physiological role of these cells in glucose homeostasis.
      Several of these characteristics are emphasized: a high-capacity system for
      glucose transport; glucose phosphorylation by the high-Km glucokinase (GK), which
      is rate-limiting for glucose metabolism and determines physiologically the
      glucose dependency curves of many processes in beta-cell intermediary and energy
      metabolism and of insulin release and is therefore viewed as glucose sensor;
      remarkably low activity of lactate dehydrogenase and the presence of effective
      hydrogen shuttles to allow virtually quantitative oxidation of glycolytic NADH;
      the near absence of glycogen and fatty acid synthesis and of gluconeogenesis,
      such that intermediary metabolism is primarily catabolic; a crucial role of
      mitochondrial processes, including the citric acid cycle, electron transport, and
      oxidative phosphorylation with FoF1 ATPase governing the glucose-dependent
      increase of the ATP mass-action ratio; a Ca(2+)-independent glucose-induced
      respiratory burst and increased ATP production in beta-cells as striking
      manifestations of crucial mitochondrial reactions; control of the membrane
      potential by the mass-action ratio of ATP and voltage-dependent Ca2+ influx as
      signal for insulin release; accumulation of malonyl-CoA, acyl-CoA, and
      diacylglycerol as essential or auxiliary metabolic coupling factors; and
      amplification of the adenine nucleotide, lipid-related, and Ca2+ signals to
      recruit many auxiliary processes to maximize insulin biosynthesis and release.
      The biochemical design also suggests certain candidate diabetes genes related to
      fuel metabolism: low-activity and low-stability GK mutants that explain in part
      the maturity-onset diabetes of the young (MODY) phenotype in humans and
      mitochondrial DNA mutations of FoF1 ATPase components thought to cause late-onset
      diabetes in BHEcdb rats. These two examples are chosen to illustrate that
      metabolic reactions with high control strength participating in beta-cell energy
      metabolism and generating coupling factors and intracellular signals are steps
      with great susceptibility to genetic, environmental, and pharmacological
      influences. Glucose metabolism of beta-cells also controls, in addition to
      insulin secretion and insulin biosynthesis, an adaptive response to excessive
      fuel loads and may increase the beta-cell mass by hypertrophy, hyperplasia, and
      neogenesis. It is probable that this adaptive response is compromised in diabetes
      because of the GK or ATPase mutants that are highlighted here. A comprehensive
      knowledge of beta-cell intermediary and energy metabolism is therefore the
      foundation for understanding the role of these cells in fuel homeostasis and in
      the pathogenesis of the most prevalent metabolic disease, diabetes.

PMID- 8549870
TI  - Report of the American Diabetes Association's Task Force on standardization of
      the insulin assay.
AB  - Recent large-scale epidemiological studies demonstrate that blood concentrations
      of immunoreactive insulin predict the development of NIDDM and IDDM and are
      associated with the risk of several degenerative diseases, such as coronary and
      peripheral vessel atherosclerosis, hypertension, and dyslipidemia. The
      reliability of these measurements is dependent on a biological assay that has not
      been well standardized between laboratories. Recognizing this, the American
      Diabetes Association organized a task force to assess comparability of blood
      insulin measurements between laboratories and to suggest techniques to improve
      comparability. The task force found that identical serum and plasma samples
      measured in different laboratories produced widely disparate values that were
      unacceptable for population comparisons. Use of a single reference standard did
      little to improve comparability. Assay characteristics such as linearity,
      recovery, accuracy, and cross-reactivity to proinsulin and its primary conversion
      intermediates varied among the laboratories, and they did not readily explain
      differences in the measurements made from assay to assay. Use of the same assay
      kit in different laboratories did not always ensure comparable measurements.
      Linear regression of assay results from one laboratory to an arbitrarily chosen
      reference assay greatly improved comparability and demonstrated the potential
      value in comparing each assay to a reference method. The task force report
      defines acceptable assay characteristics and proposes a three-step process of
      insulin assay proficiency and comparability. A central reference assay and
      ongoing sample exchange will be needed to allow reliable comparisons of insulin
      measurements made in different laboratories. Rigorous quality control and
      continuous quality improvement are needed to maintain reliability of the insulin
      measurement.

PMID- 8549871
TI  - Expression and functional activity of glucagon, glucagon-like peptide I, and
      glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells.
AB  - Rat pancreatic alpha- and beta-cells are critically dependent on hormonal signals
      generating cyclic AMP (cAMP) as a synergistic messenger for nutrient-induced
      hormone release. Several peptides of the glucagon-secretin family have been
      proposed as physiological ligands for cAMP production in beta-cells, but their
      relative importance for islet function is still unknown. The present study shows
      expression at the RNA level in beta-cells of receptors for glucagon, glucose
      dependent insulinotropic polypeptide (GIP), and glucagon-like peptide I(7-36)
      amide (GLP-I), while RNA from islet alpha-cells hybridized only with GIP receptor
      cDNA. Western blots confirmed that GLP-I receptors were expressed in beta-cells
      and not in alpha-cells. Receptor activity, measured as cellular cAMP production
      after exposing islet beta-cells for 15 min to a range of peptide concentrations,
      was already detected using 10 pmol/l GLP-I and 50 pmol/l GIP but required 1
      nmol/l glucagon. EC50 values of GLP-I- and GIP-induced cAMP formation were
      comparable (0.2 nmol/l) and 45-fold lower than the EC50 of glucagon (9 nmol/l).
      Maximal stimulation of cAMP production was comparable for the three peptides. In
      purified alpha-cells, 1 nmol/l GLP-I failed to increase cAMP levels, while 10
      pmol/l to 10 nmol/l GIP exerted similar stimulatory effects as in beta-cells. In
      conclusion, these data show that stimulation of glucagon, GLP-I, and GIP
      receptors in rat beta-cells causes cAMP production required for insulin release,
      while adenylate cyclase in alpha-cells is positively regulated by GIP.

PMID- 8549872
TI  - Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an alternatively
      spliced human islet-cell cDNA, tissue distribution, physical mapping, and
      identification of a polymorphic genetic marker.
AB  - Pancreatic beta-cell mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH)
      plays a major role in glucose-induced insulin secretion. Decreased activity of
      this enzyme has thus been proposed to play a role in the pathogenesis of NIDDM.
      Cloning of human insulinoma mGPDH cDNAs disclosed the existence of two variant
      transcripts with different 5' ends. Reverse transcription polymerase chain
      reaction (PCR) confirmed the presence of both mGPDH mRNAs in purified native
      human pancreatic islets and other tissues. A major 6.5-Kb mGPDH transcript was
      detected by Northern blot analysis in RNA from human and rat pancreatic islets,
      with distinctly lower levels in other human tissues, indicating that previously
      reported high mGPDH enzymatic activity in beta-cells is determined by high
      transcript levels. The mGPDH gene was mapped to chromosome 2 by PCR analysis of
      genomic DNA from human/rodent somatic cell hybrids, and five independent
      overlapping yeast artificial chromosome (YAC) clones containing the mGPDH
      sequence were identified from the Centre d'Etude du Polymorphisme Humain YAC
      library. Analysis of these YAC clones identified a highly polymorphic chromosome
      2q21-q33 dinucleotide repeat genetic marker (D2S141) physically linked to the
      mGPDH gene. These studies provide the means to investigate the role of the human
      mGPDH gene in the pathogenesis of NIDDM and illustrate the value of a novel
      strategy to identify genetic markers for diabetes candidate genes.

PMID- 8549874
TI  - Comment on the DCCT report. Diabetes Control and Complications Trial.

PMID- 8549873
TI  - Identification of microsatellite markers near the human genes encoding the beta
      cell ATP-sensitive K+ channel and linkage studies with NIDDM in Japanese.
AB  - ATP-sensitive K+ (KATP) channels play a key role in stimulus-secretion coupling
      in pancreatic beta-cells. Recent studies have shown that the beta-cell KATP
      channel comprises two subunits: a novel member of the inwardly rectifying K+
      channel family, designated BIR and expressed at highest levels in pancreatic
      islets, and the sulfonylurea receptor (SUR). Moreover, the genes encoding these
      two proteins are adjacent to one another on human chromosome 11. Genetic factors
      contribute to the development of NIDDM, and it seems likely that mutations in
      genes encoding proteins involved in insulin secretion or action may contribute to
      NIDDM susceptibility. The present study examined the contribution of the linked
      BIR and SUR genes to the development of NIDDM. These genes were localized to the
      same yeast artificial chromosome as two microsatellite DNA polymorphisms, D11S902
      and D11S921. These microsatellite DNA polymorphisms were typed in 140 Japanese
      NIDDM-affected sib pairs. There was no evidence for linkage between these markers
      and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not
      play a major role in susceptibility to NIDDM in Japanese.

PMID- 8549875
TI  - Molecular mechanisms of liver fibrogenesis--a homage to the role of activated fat
      storing cells.
AB  - During the last few years, considerable progress has been made in the dissection
      of cellular and molecular mechanisms of hepatic fibrogenesis. The disease,
      initiated by hepatocellular damage and perpetuated by inflammatory reactions,
      results not only in an overall increase in extracellular matrix (ECM) but also in
      molecular and histological rearrangement of virtually all matrix molecules
      including collagens, structural glycoproteins, proteoglycans and hyaluronan.
      These alterations of ECM cause severe clinical (e.g. hemodynamic) complications
      and further metabolic changes in the whole organ. Perisinusoidal fat (retinoid)
      storing cells have been identified as the (precursor) cell type mainly
      responsible for matrix production in the diseased liver. However, these cells
      have to be activated, i.e. stimulated to proliferate, to transform phenotypically
      to myofibroblasts and to express matrix genes before full competency for
      fibrogenesis is reached. Multiple cell interactions with Kupffer cells,
      platelets, endothelial cells and hepatocytes mediated by various cytokines and
      growth factors (e.g. TGF-beta 1, TGF-alpha, PDGF, FGF, IGF-1) are involved in the
      mechanism of fat-storing cell activation which is the common and central
      pathogenetic mechanism in fibrogenesis. A three-step cascade model of fat-storing
      cell activation is proposed, which offers target mechanisms for possible anti
      fibrotic interventions.

PMID- 8549876
TI  - Esophageal function and occurrence of Barrett's esophagus in Zollinger-Ellison
      syndrome.
AB  - Manifestations of esophageal disease are present in up to 60% of patients with
      Zollinger-Ellison syndrome (ZES), although esophageal function has been studied
      in only a few patients and the prevalence of Barrett's mucosa is unknown in these
      patients. It is unclear whether the high prevalence of esophageal disease is
      related to gastric acid hypersecretion alone or to abnormalities of esophageal
      motility or lower esophageal sphincter (LES) function in addition. To address
      these issues in the present study esophageal function was evaluated prospectively
      in 92 consecutive patients with ZES (66 with active disease, 26 disease-free
      after curative resection) seen during a 1-year period after controlling acid
      hypersecretion. In the patients with active disease the mean basal acid output
      (BAO) was 33 +/- 3.0 mEq/h, the maximal acid output (MAO) was 56 +/- 4.0 mEg/h,
      fasting serum gastrin was 8,736 +/- 4,813 pg/ml and duration of disease prior to
      study was 12.5 +/- 2.0 years. At the time of manometry, gastric acid secretion
      was controlled in all patients and no patient had evidence of gastroesophageal
      reflux disease at upper gastrointestinal endoscopy. Esophageal manometry revealed
      normal motility in 85% of patients. Eleven percent had low LES pressures, and
      only 1% of patients had an elevated LES pressure. The frequency of Barrett's
      mucosa (3%) was similar to that found in the general population but much less
      than that reported in patients with idiopathic GERD. No correlation was noted
      between LES pressures or manometric abnormalities and the fasting serum gastrin,
      BAO, MAO or the presence or absence of multiple endocrine neoplasia type I or
      previous vagotomy. Esophageal manometric results and LES pressure were similar in
      disease-free patients and those with active ZES. In conclusion, these results
      suggest that hypergastrinemia or other disease-specific abnormalities are not
      contributing to the high incidence of esophageal disease in patients with ZES
      because esophageal function in patients with ZES is similar to normals.
      Specifically, motility disorders in patients with ZES occur in similar frequency
      to normals, and LES pressure is normal in most patients. Despite the high levels
      of acid secretion and prominence of symptoms, the occurrence of Barrett's mucosa
      was uncommon (3%) raising the possibility of additional protective mechanisms in
      patients with ZES.

PMID- 8549877
TI  - Mucosal ulceration in isolated amphibian stomachs in vitro. Roles of nutrient
      HC03- and endogenous prostaglandins.
AB  - We examined the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on
      mucosal ulceration in isolated bullfrog stomachs and investigated the roles of
      endogenous prostaglandins (PGs) and nutrient HCO3- in the mucosal protection in
      vitro. Gastric sacs were prepared by separation from the muscle layer and
      incubation for 1-8 h in HCO3--Ringer's solution gassed with 95% 02/5% CO2 or PO3(
      )4-Ringer's solution gassed with 100% 02 in the presence of histamine (1 x 10(-4)
      M). Under these conditions, multiple ulcers developed in the mucosa only when the
      gastric sacs were incubated in HCO3--free nutrient solution; both the number and
      severity of ulcers increased with time and reached a maximum after 6 h of
      incubation. Luminal pH was decreased because of stimulation of acid secretion by
      histamine, irrespective of whether the mucosa was bathed in Ringer's solution
      with or without HCO3-, while gastric potential difference was reduced only in the
      mucosa bathed in HCO3--free nutrient solution. 16,16-Dimethyl PGE2 added to the
      nutrient side significantly reduced the number of ulcers developed in the mucosa
      bathed in HCO3--free nutrient solution. In contrast, indomethacin and aspirin,
      but not salicylate, caused ulceration even in the mucosa bathed in HCO3--nutrient
      solution. Histamine-induced acid secretion was reduced by 16,16-dimethyl PGE2 but
      not affected by these NSAIDs. In conclusion, ulceration of the isolated gastric
      mucosa in the presence of acid depends upon either a deficiency of endogenous PGs
      or a lack of nutrient HCO3-/CO2.

PMID- 8549878
TI  - Indomethacin interferes with epidermal growth factor binding and proliferative
      response of gastric KATO III cells.
AB  - Indomethacin induces gastric ulcerations and decreases cell proliferation in the
      gastric ulcer margin. Since epithelial cell proliferation is under control of
      epidermal growth factor (EGF), we studied whether indomethacin may affect
      specific binding of [125I]-EGF to its receptors in cultured human gastric KATO
      III cells. To assess effects of EGF, indomethacin and their combination on cell
      proliferation, KATO III cells were incubated for 24 h with either (a) vehicle (b)
      indomethacin (doses from 10(-5) to 10(-3) M), EGF (doses 0.01, 0.05 or 0.1
      microgram/ml) or (d) a combination of b and c, and the bromodeoxyuridine labeling
      index was determined. Indomethacin in a dose which did not affect cell viability
      significantly (by 21.5%) decreased [125I]-EGF binding to the KATO III cells and
      decreased the bromodeoxyuridine labeling index. Epidermal growth factor
      significantly increased cell proliferation and increased the labeling index from
      28.9 +/- 0.6% in the vehicle group to 36.2 +/- 0.5%. Co-treatment with
      indomethacin significantly reduced the proliferative response of KATO III cells
      to EGF. In conclusion, indomethacin, in a dose which does not affect cell
      viability, decreased binding of EGF to cultured gastric KATO III cells and
      decreased their proliferative response to EGF.

PMID- 8549879
TI  - Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not
      related to cigarette smoking.
AB  - Patients with ulcerative colitis are usually non- or ex-smokers in contrast to
      Crohn's disease where smoking is common. Abnormalities of quantity and quality of
      intestinal mucus have been postulated in the pathogenesis of these diseases. It
      is possible that smoking habit may exert its effects via changes in mucus in
      inflammatory bowel disease. We have therefore studied incorporation of N
      acetylglucosamine into synthesized colonic mucin in explants from 85 controls
      with normal colonoscopic appearances and histology, including 27 smokers and 58
      nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's
      disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into
      normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation
      was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4
      dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative
      colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal
      in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p
      = 0.44). No significant relationship was found between cigarette smoking habits
      and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0
      +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD)
      6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus
      glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to
      normal levels in active disease and that synthesis is increased in Crohn's
      disease. There is no effect of smoking on mucus synthesis by control biopsies
      suggesting that the differences seen in inflammatory bowel disease are not
      related to cigarette smoking.

PMID- 8549880
TI  - Incidence of inflammatory bowel disease in southeastern Norway: evaluation of
      methods after 1 year of registration. Southeastern Norway IBD Study Group of
      Gastroenterologists.
AB  - To assess the feasibility of a prospective incidence study of inflammatory bowel
      disease (IBD), the registration methods and incidence figures during 1990 were
      evaluated. The study was a collaboration between 14 hospitals in an area of close
      to one million inhabitants. Common diagnostic criteria for ulcerative colitis
      (UC), Crohn's disease (CD) and indeterminate colitis (IND) were established prior
      to the start of the study. There was an overall incidence rate for IBD of 19.3
      per 10(5) inhabitants, with 10.6 for UC, 5.1 for CD and 3.6 for IND. The age
      specific incidence rates showed a peak between 25 and 34 years for UC and between
      15 and 25 for CD. There was a male predominance for UC and a female preponderance
      for CD. These results are comparable with the previous registrations in western
      and northern areas of Norway.

PMID- 8549881
TI  - Medication with ursodeoxycholic acid enhances the biliary clearance of
      polyethylene glycol 900, but not mannitol.
AB  - Ursodeoxycholic acid (UDCA) is a nontoxic bile acid currently used in the
      treatment of different cholestatic diseases. This bile acid is also considered to
      be a 'hypercholeretic bile acid'. The effects of daily administration of UDCA on
      bile flow and the bile acid secretion rate in man are not fully known. The aim of
      this study was to explore the effects by UDCA on bile flow and its different
      functions. The biliary clearances of polyethylene glycol 900 (PEG 900) and
      mannitol were measured simultaneously in patients with an indwelling T tube after
      cholecystectomy. One group (n = 6) were given UDCA (10 mg/kg/day) for at least 14
      days before the investigation and a control group (n = 8) received no bile acid
      treatment. The bile secretion was studied in acute experiments where bile was
      drained for 6 h. The bile plasma ratio for PEG 900 was 31 and that for mannitol
      was 0.7 which corresponds well with the results obtained in different animal
      species. The relationship between bile flow and the bile salt secretion rate, as
      expressed by linear regression analysis, showed no difference between the 2
      groups (control y = 0.22 + 0.012x, r = 0.61, p < 0.001; UDCA y = 0.20 + 0.016x, r
      = 0.88, p < 0.001). The relationship between the biliary clearance of PEG 900 and
      the bile salt secretion rate, as expressed with linear regression analysis,
      showed a significantly steeper slope for the UDCA-treated patients (control y =
      8.1 + 0.34x, r = 0.41, p < 0.05; UDCA y = 5 + 1.58x, r = 0.78, p <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549882
TI  - Influence of ceruletid on gallbladder contraction: a possible prophylaxis of
      acute acalculous cholecystitis in intensive care patients?
AB  - The purpose of this study was to investigate the utility of repeated applications
      of ceruletid to reduce gallbladder volume and its feasibility as a means of
      prophylaxis of acute acalculous cholecystitis in intensive care patients. First,
      a dose-response curve of ceruletid was obtained in 20 mechanically ventilated
      patients of a surgical intensive care unit (SICU) not receiving enteral
      nutrition. An effective dose of ceruletid, defined by a 50% reduction of
      gallbladder volume was established and subsequently studied in 40 mechanically
      ventilated SICU patients on total parenteral nutrition in a prospective,
      randomized, controlled, triple-blind trial. Gallbladder volume, sludge formation
      and side effects were evaluated. A dose of 1.5 micrograms/kg body weight
      ceruletid was established as the effective dose, causing 50% reduction of
      gallbladder volume in all patients studied and reduction of gallbladder sludge in
      95%. In 67.5% of patients side effects were observed, requiring therapeutic
      intervention in 68%. It is concluded that ceruletid is effective in stimulating
      gallbladder contraction and reducing sludge formation in severely ill patients on
      intensive care units. Its routine use as prophylaxis of acute acalculous
      cholecystitis, however, may be limited by the nature, severity and frequency of
      side effects.

PMID- 8549883
TI  - Relationship of gallbladder contour, fasting volume and emptying to body size
      indices in normal subjects and patients with gallstones.
AB  - Fasting gallbladder volume and fasting gallbladder roundness index (ratio of
      anteroposterior diameter to gallbladder length) were estimated by ultrasonography
      in 182 normal subjects and 43 patients with gallstones and correlated to body
      size indices. In 20 of the normal subjects, gallbladder emptying was assessed and
      correlated to gallbladder roundness index. Gallstone patients had a larger
      fasting gallbladder volume as compared to normals (42 +/- 10 vs 22 +/- 7 (SD) ml,
      p < 0.001). Gallbladder fasting volume was found to be significantly related to
      roundness index (p < 0.001) and body surface area (p < 0.0001) in normals, but
      not in patients with cholelithiasis. Subjects with a roundness index > 0.3 showed
      a less-complete gallbladder emptying as compared to those with a roundness index
      < 0.3 (p < 0.01). It is concluded that increased body size, but not obesity
      alone, is associated with an increased gallbladder fasting volume, and that a
      rounder gallbladder tends to empty less completely.

PMID- 8549884
TI  - Beneficial effects of L-arginine on intestinal epithelial restitution after
      ischemic damage in rats.
AB  - The polyamines are involved in repair processes after intestinal ischemia.
      Arginine and ornithine, both precursors of polyamines were therefore expected to
      exert beneficial effects on mucosal barrier dysfunction. Arginine may also
      generate NO and there is support for the view that NO may be beneficial after an
      ischemic insult. Male Wistar rats were given, by gavage, isonitrogenous solutions
      of L-arginine (0.5 g/kg) or L-ornithine (0.7 g/kg) 17 and 2 h before ischemia.
      Controls received an isonitrogenous solution of casein hydrolysate (1 g/kg).
      Transient intestinal ischemia was produced in anesthetized rats by occluding the
      superior mesenteric artery for 90 min. Intestinal morphology, hydrolase
      activities, polyamine and cGMP contents, and cell proliferation rates were
      determined 4 h after reperfusion. Administration of arginine or ornithine did not
      prevent ischemic damage but accelerated morphological repair, enhanced cell
      proliferation, and polyamine content was observed. Arginine was significantly
      more effective than ornithine. Formation of cGMP was enhanced after arginine
      administration. NG-nitroarginine methylester, an inhibitor of NO synthase,
      prevented the arginine effects on mucosal repair. We conclude that arginine
      derived NO is an important mediator in the restitution of intestinal mucosa by
      minimizing cell injury during reperfusion.

PMID- 8549885
TI  - Immunohistochemical distribution and serum levels of the Ca(2+)-binding proteins
      MRP8, MRP14 and their heterodimeric form MRP8/14 in Crohn's disease.
AB  - In previous histochemical studies the distribution of the two Ca(2+)-binding
      proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 has been
      demonstrated in different inflammatory diseases. Monoclonal antibodies against
      MRP8 and MRP14 and their heterodimer MRP8/14 (27E10 epitope) were used to
      investigate immunohistochemically the distribution of these proteins in routinely
      processed small and large bowel tissues from patients with Crohn's disease (CD).
      Furthermore, we used a sandwich immunoassay to measure serum concentrations of
      MRPs in 62 patients were simultaneously assessed by the Crohn's disease activity
      index (CDAI) and the severity activity index of Goebell (SAI). In our
      immunohistochemical study, MRP8, MRP14 and heterocomplex MRP8/14 were
      demonstrated in the majority of granulocytes and macrophages in active CD.
      Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial
      cells adjacent to ulcerative and fissuring lesions in the bowel. Serum MRP8/14
      concentrations were significantly (p < 0.0001) increased in patients with active
      CD (CDAI > 150, SAI > 120). No correlations were found for level of MRP14 and
      MRP8 alone, respectively. The follow-up of individual patients with initially
      active CD showed a further increase in MRP8/14 levels during acute attacks of the
      inflammatory process. We suggest that our assay for MRP8/14 discriminates well
      between active and inactive CD and may have considerable potential in the
      analysis of clinical disease activity in CD patients. Our morphological results
      confirm the finding of increased MRP8/14 serum levels in patients with active CD.

PMID- 8549886
TI  - Long-term ingestion of lactosucrose increases Bifidobacterium sp. in human fecal
      flora.
AB  - We investigated the influence of lactosucrose on the intestinal flora of healthy
      volunteers. Eight healthy volunteers (male:female = 4:4, age 34 +/- 4 years)
      received 6 g of lactosucrose daily for 8 weeks. Fecal microflora, bacterial
      metabolites, pH, and moisture were analyzed before and after the administration
      of lactosucrose. The results showed that the number and percentage of
      Bifidobacterium sp. in relation to the total bacteria significantly increased
      during the period of lactosucrose administration. Although fecal putrefactive
      products, fatty acids, pH, moisture content, and stool volume did not show
      significant changes during the test period, the amount of fecal phenol showed a
      negative correlation with the number of Bifidobacterium sp. Fecal ammonia
      significantly decreased after 4 and 8 weeks of lactosucrose administration, and 1
      week after the end of lactosucrose administration, compared with results after a
      1-week administration of lactosucrose. When the administration was stopped, the
      percentage of Bifidobacterium sp. in relation to the total count gradually
      decreased to the same level as before the administration of lactosucrose. These
      results suggest that under physiological conditions, lactosucrose acts on the
      intestinal microflora as a growth factor of Bifidobacterium sp.

PMID- 8549887
TI  - Adverse reaction to food: assessment by double-blind placebo-controlled food
      challenge and clinical, psychosomatic and immunologic analysis.
AB  - Double-blind placebo-controlled food challenge (DBPCFC) with food items applied
      in capsules was performed in a prospective study of 17 selected patients and 34
      age- and sex-matched healthy controls in the interdisciplinary clinical setting.
      Protein immunoblotting showed no differences in antigenicity between foods in the
      capsules and the corresponding fresh foods. All patients reacted to one or more
      food substances during DBPCFC, with a doubtful reaction to placebo in 2 patients.
      Agreement between diet history and provocation was seen in 53 of 85 individual
      food challenges, 36 being positive with both examinations. In 22 (38%) of the 58
      positive provocations, the reactions were not expected from the patients'
      histories. No reaction to food or placebo occurred in the control group. Related
      to diet history, sensitivity and specificity of provocation were 62 and 63%,
      respectively, with a positive predictive value of 78%. Allergy, previous
      gastroenterologic and infectious diseases among first-degree relatives,
      immunologic abnormalities and elevation of total IgE were significantly more
      common for the patients than controls. A positive skin prick test correlated well
      with diet history, but both prick test and food antibodies correlated poorly with
      DBPCFC. Assessment by the General Health Questionnaire showed a significant
      difference towards the controls. After 3-4 months of follow-up on an individually
      based diet, 11 of 15 patients reported general improvement of their condition.
      DBPCFC may be a valuable diagnostic test in addition to dietary history as a
      basis for elimination diet on food-intolerant patients. The effect of the
      elimination diet on the symptoms may also suggest a therapeutic effect or
      provocation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8549888
TI  - Cholestasis induced hyperthyroidism after liver transplantation.
AB  - We report the case of a 68-year-old woman who underwent liver transplantation
      because of hepatitis-C-induced cirrhosis. She developed iodine-reduced
      hyperthyroidism postoperatively in temporal relation with cholestatic jaundice.
      Hepatic biopsies revealed moderate intrahepatic cholestasis and mild lobular
      inflammatory infiltration with some eosinophils. No histological evidence of
      acute graft rejection or reactivated hepatitis was found. Treatment with
      methimazole markedly reduced the serum parameters of cholestasis which, after
      subtotal thyroidectomy, returned to normal. Liver function recovered, as
      confirmed by repeated aminopyrine breath tests.

PMID- 8549889
TI  - Therapy of irritable bowel syndrome--an overview.

PMID- 8549890
TI  - Effects of reference interaural time and intensity differences on binaural
      performance in listeners with normal and impaired hearing.
AB  - OBJECTIVE: The purpose of this research was to measure the effects of reference
      interaural time and intensity differences on binaural performance in listeners
      with normal hearing and impaired hearing for a number of different binaural
      tests. Experiment 1 measures the dependence of binaural detection and
      discrimination performance on reference interaural intensity differences (IID) in
      the range of +/- 12 dB for listeners with normal hearing. Experiment 2 extends
      these measures to include reference IIDs and interaural time differences (ITD)
      for two groups of listeners with normal hearing with offsets in the range of +/-
      12 dB and +/- 300 microseconds (group 1) and +/-24 dB and +/- 600 microseconds
      (group 2). Experiment 3 includes the same tests and conditions as experiment 2
      for listeners with various hearing impairments. DESIGN: A set of psychophysical
      measurements was completed on 11 listeners with sensorineural hearing losses and
      9 listeners with clinically normal hearing. The primary measurements were a set
      of four binaural detection and interaural discrimination thresholds measured for
      two 1/3-octave bands of Gaussian noise, one centered at 500 Hz and the other at
      4000 Hz. Specifically, we measured binaural (antiphasic) detection thresholds for
      tones centered in the masking noise as well as the just-noticeable differences
      (JNDs) in IID, ITD, and interaural cross-correlation (ICC) for each of the noise
      band stimuli. All measurements were done for a number of combinations of
      reference IID and ITD. In addition to these primary measurements, several other
      measurements were made on each subject, including monaural absolute thresholds,
      monaural intensity discrimination, monaural masked thresholds, and intensity
      levels required for interaurally balanced loudness and for a centered image. All
      measurements were made using a relatively quick, adaptive procedure. RESULTS: For
      the subjects with normal hearing, measured dependencies of the IID and ITD JNDs
      using noise stimuli on reference ITD and IID are different from those previously
      reported for tonal stimuli. Binaural performance of the listeners with impaired
      hearing varies widely across subjects and tests and is generally poorer than that
      of listeners with normal hearing. CONCLUSIONS: On the basis of the results for
      subjects with hearing impairments, we have reached several conclusions. First,
      the results for the binaural measurements cannot be explained in terms of
      available monaural audiometric and psychophysical measurements on these subjects.
      Second, the subjects' binaural abilities show no significant improvement with any
      combinations in the reference values of ITD and IID, providing negative evidence
      for the hypothesis that degraded performance for some subjects may be due to
      internal interaural offsets in ITD or IID. Third, the hypothesis that binaural
      detection and ICC discrimination are related, suggested by Durlach et al (1986),
      is generally supported. Fourth, binaural detection performance is not simply
      explained in terms of sensitivities to ITD and IID.

PMID- 8549891
TI  - A comparison of binaural interactions using traditional and maximum length
      sequence evoked response paradigms.
AB  - OBJECTIVE: Two paradigms, the traditional binaural interaction (BI) paradigm and
      a maximum length sequence (MLS) BI paradigm were evaluated to investigate BI
      effects. DESIGN: Evoked response BI effects were assessed at different levels of
      the auditory pathway in two experiments. Each experiment consisted of three
      conditions: a traditional BI paradigm using conventional stimuli, a traditional
      BI paradigm using MLS stimuli, and a MLS BI paradigm using MLS techniques to
      recover kernels reflecting BIs. Eleven normal-hearing young adults served as
      subjects. RESULTS: There was evidence for BI effects on the auditory evoked brain
      stem response (ABR) and the middle latency response (MLR) using the traditional
      BI paradigm and conventional stimuli. With the same paradigm and MLS stimuli
      there was evidence for BI effects on the MLR but not the ABR. The more robust
      conventional effects may be explained by the larger amplitude evoked responses
      recorded conventionally due to the slower stimulation rates and more efficient
      signal to noise enhancement. BI effects were observed for both the ABR and MLR by
      recording BI kernels in the MLS BI paradigm. CONCLUSIONS: MLS BI kernels can be
      recorded in normal hearing adults. The MLS BI paradigm offers three potential
      advantages in recording binaural effects; avoidance of some of the methodological
      problems associated with traditional BI paradigms, faster stimulus rates
      permitting a more complete characterization of binaural rate effects, and more
      rapid data collection.

PMID- 8549892
TI  - Thresholds for auditory brain stem responses to tones in notched noise from
      infants and young children with normal hearing or sensorineural hearing loss.
AB  - OBJECTIVE: To assess the accuracy of threshold estimates determined using the
      auditory brain stem responses (ABRs) to brief tones presented in notched noise in
      a group of infants and young children with normal hearing or sensorineural
      hearing loss (SNHL). DESIGN: The thresholds for ABRs to brief duration 500, 2000,
      and 4000 Hz tones presented in notched-noise masking were evaluated in infants
      and young children with normal hearing (N = 34) or SNHL (N = 54). Tone-evoked ABR
      thresholds were compared with behavioral thresholds obtained at follow-up
      audiologic assessments, for a total of 220 comparisons. RESULTS: ABR thresholds
      for the infants with bilateral normal hearing were 23.6, 12.9, and 12.6 dB nHL
      for 500, 2000 and 4000 Hz, respectively. Most (92 to 100%) infants with normal
      hearing showed ABRs to 30 dB nHL tones. Across all subjects (i.e., those with
      normal hearing and those with impaired hearing), high ( > or = 0.94) correlations
      were found between the ABR and behavioral thresholds. The mean differences
      between ABR (dB nHL) and behavioral (dB HL) thresholds across all subjects were
      8.6, -0.4, and -4.3 dB for 500, 2000, and 4000 Hz, respectively. Overall, 98% of
      the ABR thresholds were within 30 dB of the behavioral thresholds, 93% were
      within 20 dB, and 80% were within 15 dB. CONCLUSIONS: These threshold results for
      the ABR to brief tones in notched noise obtained for infants and young children
      are similar to those obtained in similar studies of adults. The technique may be
      used clinically with reasonable accuracy to estimate pure-tone behavioral
      thresholds in infants and young children who are referred for diagnostic
      threshold ABR testing.

PMID- 8549893
TI  - Effect of high-frequency interrupted noise exposures on evoked-potential
      thresholds, distortion-product otoacoustic emissions, and outer hair cell loss.
AB  - The effect of high-frequency interrupted noise exposures on evoked potential (EP)
      thresholds, distortion-product otoacoustic emissions (DPOAEs), and status of the
      outer hair cells was studied with the aim of understanding the correspondence
      among the three measures. Animal subjects were exposed to an octave band noise
      centered at 4 kHz at 85 dB SPL for 6 hr/day for 10 days. EP and DPOAE recordings
      were made before the exposure and on days 1, 2, 4, 6, 8, and 10 of exposure. A
      final set of measurements were made 5 days after the last exposure, following
      which the animals were sacrificed and their cochleas were examined using scanning
      electron microscopy. Both EPs and DPOAEs showed a worsening of auditory function
      after the first exposure and then showed a progressive recovery toward baseline.
      However, there was no consistent relationship between changes in EP thresholds
      and changes in DPOAEs nor were there any systematic changes in outer hair cells
      that corresponded with the changes in DPOAEs. Furthermore, EP thresholds often
      revealed considerable deficits in function while DPOAEs were normal.

PMID- 8549894
TI  - Effects of noise exposure, race, and years of service on hearing in U.S. Army
      soldiers.
AB  - Over the last two decades the U.S. Army has instituted a comprehensive hearing
      conservation program (HCP) to reduce the prevalence of hearing loss in soldiers
      and civilian employees. As a component of this program, hearing threshold levels
      (HTLs) are stored in a central computerized Army-wide hearing conservation data
      registry. The aim of this study was to analyze the hearing threshold data to
      compare the hearing loss among soldiers representing different (1) race groups,
      (2) noise exposure groups, and (3) duration of military service. HTLs were age
      corrected using data base B values from ISO 1999 (1990). As may be expected,
      soldiers exposed to high noise levels had significantly poorer hearing than the
      group of soldiers with limited noise exposure. On the average, results indicated
      a significant difference in HTLs among the race groups with black soldiers having
      the most sensitive hearing and white soldiers having the poorest. Also, subjects
      with greater durations of military service had the least sensitive hearing.
      Finally, race and years of service factors were found to interact in their effect
      on HTL. The findings are discussed in terms of implications of race differences,
      normative data, and effectiveness of the U.S. Army HCP.

PMID- 8549895
TI  - The transmission of phoneme-level information by multichannel tactile speech
      perception aids.
AB  - Current research on the effectiveness of tactile aids for speech perception by
      hearing-impaired persons suggests that substantial training, lasting over months
      or years, is necessary for users to achieve maximal benefits from a tactile
      device. A number of studies have demonstrated the usefulness of training programs
      that include an analytic component, such as phoneme training, together with more
      synthetic tasks such as sentence identification and speech tracking. However,
      particularly in programs for children, it is desirable to structure training
      experiences so that easy distinctions are trained first, and more difficult
      distinctions are approached only later in training. In the present study, a
      systematic evaluation of phoneme-level information provided by the Tactaid VII, a
      multichannel tactile aid, was performed. Adult subjects were tested in minimal
      pairs and closed set phoneme discrimination and identification tasks under
      tactile aid alone, speechreading alone, and speechreading plus tactile aid
      conditions, to provide an inventory of stimulus identifiability and permit
      ranking of discriminations as easy or more difficult. Because these rankings
      might differ as a function of coarticulation effects, three different vowel
      contexts were tested for consonant stimuli. Results indicated that there were
      indeed considerable differences across vowel contexts, and that the /ae/ vowel
      context yielded the most identifiable stimuli. These data could be used by
      teachers and therapists to construct viable stimulus sets for training programs
      for tactile aid users.

PMID- 8549897
TI  - Discrimination of multichannel-compressed speech in noise: long-term learning in
      hearing-impaired subjects.
AB  - OBJECTIVE: It takes time for an individual to obtain optimal benefit from a new
      hearing aid. This research examines the possibility that similar long-term
      learning can be seen in consecutive laboratory studies of multichannel
      compression (MCC). DESIGN: Three studies of different parameters of MCC
      processing, carried out over the period of 1 yr, included the same 15 hearing
      impaired subjects and one identical MCC-processing condition. The full-range MCC
      had 8, 12, or 16 independent frequency channels, using a Robinson-Huntington
      compression algorithm. The City University of New York nonsense syllable test was
      modified to facilitate digital signal processing and control of the experiments.
      The subjects discriminated nonsense syllables (a female and a male voice) in
      speech spectrum noise at -5 to 15 dB signal-to-noise ratios (S/N). Conditions
      were not ideal for learning: subjects' experience with MCC-processed speech was
      limited to the laboratory and no trial-by-trial feedback was provided. Percent
      correct syllable discrimination and consonant confusion matrices were compared
      across experiments to observe the subjects' learning to listen with MCC
      processing. RESULTS: All subjects combined, and 14 of 15 individual subjects,
      showed significant improvement across experiments. For the subject showing the
      maximum learning, the percent correct difference between the first and third
      experiments was equivalent to a 9.8 dB increase in S/N. The average learning for
      all subjects was equivalent to +3 dB S/N. The difference between the consonant
      confusion matrices for the first and third experiments indicated that improved
      discrimination occurred for both manner and place information. The pattern of
      changes in the confusion matrices was consistent with improved use of the high
      frequency information supplied by the MCC signal processing. A brief comparison
      of the results of the first experiment with a fourth experiment indicated that
      the learning was specific to MCC processing because it did not generalize to
      frequency-shaped linear amplification which was also studied in those two
      experiments. CONCLUSIONS: These results indicate that specific long-term learning
      occurred for hearing-impaired subjects listening to nonsense syllables in noise
      with 8- to 16-channel MCC processing. Since previous experiments have provided
      subjects with much less listening experience, the results suggest that MCC with
      large numbers of channels may be much more beneficial for the hearing-impaired
      individuals than the results of previous experiments had indicated.

PMID- 8549896
TI  - Preferred listening levels for linear and slow-acting compression hearing aids.
AB  - OBJECTIVE: The purpose of the present experiment was to determine the
      relationship between most comfortable listening level and preferred listening
      levels for linear and slow-acting compression hearing aids as a function of
      variations in speech and noise level. DESIGN: A digital hearing aid test system
      was used to simulate six hearing aids having compression ratios of 1, 1.5, 2, 3,
      5, and 10:1. Speech was presented in three different noises (vent, apartment, and
      cafeteria), with speech input level being varied (55, 70, 85 dB SPL). Subjects
      were 20 listeners with sensorineural hearing loss (half with a dynamic range < or
      = 30 dB and half with a dynamic range >30 dB). The boundaries of the most
      comfortable listening range were measured to estimate most comfortable listening
      level. Preferred listening level was measured by having subjects adjust the
      output of the hearing aid for satisfactory listening. RESULTS: On average, the
      deviation of preferred listening level from most comfortable loudness (MCL) was
      less than 5 dB. Dynamic range, noise type, and input level were all found to have
      small, but significant, effects on the deviation of preferred listening level
      from MCL. On average, subjects with a small dynamic range listened slightly below
      MCL, and subjects with a larger dynamic range listened slightly above MCL. For
      favorable signal-to-noise ratios, preferred listening levels were highest for
      high input levels and for conditions that resulted in high output levels before
      level adjustment. Although the pattern of average performance differed slightly
      at poorer signal-to-noise ratios, all preferred listening levels were close to
      MCL. CONCLUSIONS: The gain of a slow-acting compression hearing aid should place
      the output within 5 dB of MCL. The output for low and medium inputs should
      approximate MCL and the output for high input levels should be slightly above
      MCL. This pattern of gain may be obtained with mild compression ratios and a gain
      rule that places a speech input of 70 dB at MCL.

PMID- 8549898
TI  - Frequency variation of spontaneous otoacoustic emissions during a naturally
      occurring menstrual cycle, amenorrhea, and oral contraception: a brief report.
AB  - OBJECTIVE: The frequencies of one subject's spontaneous otoacoustic emissions
      (SOAEs) were tracked intermittently for 295 days. DESIGN: The first 40 days
      encompassed a normal menstrual cycle. During the next 186 days, the subject
      exhibited amenorrhea. For the last 69 days, she took oral contraceptives
      prescribed by her doctor to reestablish menstrual function. RESULTS: Anovulation,
      as evidenced by amenorrhea or induced by oral contraception, reduced the
      fluctuation of SOAE frequencies relative to the naturally occurring menstrual
      cycle. CONCLUSIONS: Future research might fruitfully be aimed at monitoring SOAE
      frequencies in humans and animals to determine whether the fluctuations can
      provide a noninvasive measure of the functioning of the pituitary-gonadal axis.

PMID- 8549899
TI  - Medical-legal evaluation of hearing loss: are methods of allocation testable?

PMID- 8549900
TI  - [Thoughts on renewed tasks of medicine].

PMID- 8549901
TI  - [Transthoracic and transesophageal echocardiographic study in aortic valve
      replacement with pulmonary valve autograft].
AB  - Eleven patients who underwent pulmonary valve autograft to aortic position with
      placement of bovine pericardial prosthesis in pulmonary position were studied
      with echocardiography. Transthoracic echocardiography, was performed on all
      patients before surgery. Transesophageal echocardiograms were practiced during
      the surgical procedure. The latter technique aided in immediate postoperative
      evaluation. Transthoracic and transesophageal echocardiography provide a
      practical and valuable means of investigating the pre, trans and postoperative
      conditions of patients undergoing Ross surgery.

PMID- 8549903
TI  - [Observed vs expected mortality in the emergency service of a general hospital.
      Evaluation by the APACHE II and multiple organ failure classification systems].
AB  - Problem that originated the investigation: It was not known if the observed
      mortality in the Emergency room of the Tijuana General Hospital was lower, equal
      or higher, than the expected mortality. OBJECTIVES: 1) Evaluate in a prospective
      fashion the mortality rate in that hospital service, and then compare that rate
      with an expected mortality rate proposed in the literature (Role). 2) Determine
      the prognostic value in our hospital of the Multiple Organ Failure classification
      system (MOF). The Multiple Organ Failure classification system showed in our
      study an excellent predicting capacity for mortality.

PMID- 8549902
TI  - [Causes of death in congenital hypothyroidism. An autopsy study].
AB  - Children with congenital hypothyroidism are prone to die unexpectedly. In order
      to test this hypothesis, the primary and contributing causes of death were
      studied in a case series of sixteen consecutive children coming to autopsy. Four
      patients with absent thyroid died undiagnosed and untreated. The remaining twelve
      cases had documented hypothyroidism with low T3 and T4 levels. Diagnosis was
      established after the age of two months. Nine of the sixteen cases died
      unexpectedly, three while in the hospital and six at home. Autopsy findings
      suggested bronchoaspiration in five and heart failure in four. The remaining
      seven cases died under predictable circumstances with serious infections.
      Children with congenital hypothyroidism with delayed treatment may die
      unexpectedly as a result of the organic dysfunction caused by their primary
      disease.

PMID- 8549904
TI  - [The aging process].

PMID- 8549905
TI  - [Impact of organ transplantation 40 years after the beginnings].

PMID- 8549907
TI  - ["Miguel F. Jimenez lecture. The paradigm of modern medicine: molecular
      genetics].

PMID- 8549908
TI  - [Evaluation of Mexican biomedical journals].
AB  - We present the evaluation procedures of Biomedical Journals, performed by the
      Journal Committee of the Centro Nacional de Informacion y Documentacion sobre
      Salud (CENIDS) for the preparation of CR-ROM ARTEMISA 2 (Edited health
      information articles in Mexico), which contains a database of the complete text
      of articles appearing in the journals of the highest quality published in Mexico.

PMID- 8549906
TI  - [Historical considerations on the diagnosis of diabetes mellitus].
AB  - The concept if diabetes mellitus has suffered multiple and interesting
      definitions throughout the time. The initial acknowledgement was based on the
      observations made by lay people and later by clinicians. Experimental work on the
      genesis of diabetes mellitus was remarkable not only on the physiopathology of
      diabetes it self, but also on metabolic processes in general. At the present,
      diabetes mellitus is considered as an heterogeneous disease formed by various
      syndromes of different etiology. Moreover diabetes mellitus has become an
      important public health problem due to the chronic complications as cause of
      disabilities and death. In Mexico, recent surveys have confirmed that the
      prevalence of diabetes mellitus is high and shows a geographic distribution which
      deserves to establish particular and specific health programs.

PMID- 8549909
TI  - [A novel treatment of cholera by a Mexican physician in the 19th century].
AB  - Doctor Felipe Castillo, head of the Hospital de San Pablo during the cholera
      epidemic of 1850, used "Salty water" as treatment for the patients who attended
      the hospital. The etiology and pathogenesis of this sickness were unknown in
      those days, so Castillo's conduct was surprising. This study is based on an
      unpublished report, classified as anonymous, that Castillo gave to the Governor
      of Mexico City during the cholera epidemic.

PMID- 8549910
TI  - [Chronic diarrhea and Cryptosporidium in diabetic patients with normal lymphocyte
      subpopulation. 2 case reports].
AB  - Two cases of diabetic patients with normal TCD4+ cell count with chronic
      diarrhoea and Cryptosporidium are described herein. In both cases serologic tests
      for HIV were negative. The fact that these patients developed a pathology usually
      seen in presence of low TCD4+ cell counts suggests that some immune defect other
      than cellular might be involved in the pathogenesis of this infection. Authors
      concluded that intentional search for Cryptosporidium should be considered in the
      study of the diabetic patient with chronic diarrhoea.

PMID- 8549912
TI  - [Ultrasound of the biliary tract].

PMID- 8549911
TI  - [A case of rabies encephalitis with long survival. Clinical pathological
      correlations].
AB  - We present a case of a 22 year old male patient who developed a rabies
      encephalomyelitis with evolution of six weeks, treated first as a psychiatric
      disorder and later as an encephalitis. This case had the following important
      features; 1--A long time with the disease: usually the patients die into the
      first eight days after diagnosis; 2--The evident reactive gliosis; 3--Almost all
      the studied fields showed inclusion bodies in both supratentorial and
      infratentorial portions; 4--The hippocampus and spinal cord neurons had many or
      unique Negri bodies and some of those were giant; 5--Microglia proliferation and
      free acidophilus bodies. All those microscopic features mean a long evolution
      time that is rarely seen in this illness; in medical literature we found only ten
      long duration cases.

PMID- 8549913
TI  - [Apoptosis in the pathogenesis and treatment of disease].

PMID- 8549914
TI  - [New mechanisms of analgesic action. I].

PMID- 8549915
TI  - [Dengue in Mexico. Current epidemiological situation].

PMID- 8549916
TI  - [Original Mexican contributions to medicine. Praziquantel and neurocysticercosis.
      An honorable and transcendent Mexican priority].

PMID- 8549917
TI  - [Victor Rubio and Rodolfo Limon. Initiators of the interventionist cardiology].

PMID- 8549918
TI  - [Human rights of the physician].
AB  - The physician rights may be classified in those related with his quality as a
      person, and those derived from his relationship with his patients and the
      institution to which he belongs. Among the first, liberty of expression, legal
      security, right of free association, the right of a dignified social position and
      neutral attitude towards the commitment of giving medical attention to whomever
      the patient may be. He has the right to receive a full and up-to-date training
      oriented to serve the community, supported by health institutions, and to have
      the means of utmost quality to give medical attention of the highest standard.

PMID- 8549919
TI  - [Ethical principles of medical research using human subjects].
AB  - Medical research involving human beings has contributed to the advancement of
      knowledge about prevention, diagnosis, and treatment of the diseases. All
      researchers, independently of their working country, must always have in mind the
      international ethical principles as a guide in the solution for the ethical
      problems that they may face during the practice of research activities on human
      beings. Among the ethical principles more widely accepted in the western culture,
      three are of upstanding importance for clinical research in human subjects: a)
      the principle of respect for persons, based upon the conception of the individual
      as an autonomous being, capable of shaping and directing his own life; b) the
      principle of beneficence, that refers to the ethical obligation to maximize
      benefits and to minimize harms and wrongs; and c) the principle of justice, that
      refers to the ethical imperative to treat each person in accordance with what is
      morally right and proper. The application of these theoretical principles to the
      real life problems is not easy, especially in cases in which the research group
      belong to a developed country, and the group of participating subjects, to an
      underdeveloped one. It is worthy to ask if the three mentioned ethical principles
      are universally acknowledged, and whether in the Latin American and Caribbean
      region, these principles are recognized as the gold rules for the solution of the
      ethical problems of medical research involving human subjects.

PMID- 8549920
TI  - [A program of surveillance of surgical wounds].

PMID- 8549921
TI  - [Uterine perforation and localization of an IUD in the bladder associated with
      bladder calculosis. Report of a case and review of the literature].
AB  - A case is reported of the presence of an intrauterine device into the bladder due
      to uterine perforation with calculus formation in a 39 year old woman, with two
      pregnancies after its installation. The patient was seen for complaints of pelvic
      pain, pollakiuria, dysuria and tenesmus, without uterine sintomatology. The case
      was studied in July of 1993 in the General Hospital "Vicente Guerrero" of
      Acapulco. To our knowledge only 19 previous cases have been reported in the
      literature of migration of an intrauterine device into the bladder with calculus
      formation. The literature is reviewed and we discuss the clinico-radiological
      findings.

PMID- 8549922
TI  - [Urologic lesions in gynecologic and uro-gynecologic surgery. Two years of
      hospital experience].
AB  - We are reporting the most frequent urologic injuries of the gynecologic and
      urogynecologic surgeries at the National Institute of Perinatology in Mexico
      City. From the period of March 1993 to February 1995. There were performed 3,452
      surgeries. Of this, 2,971 were gynecologic and 481 urogynecologic cases. We found
      20 patients with injury to the inferior urinary tract. The most frequent type of
      injury found was by puncture and blunt, in eight cases respectively and cutting
      in four. The transoperatory diagnostic of injury was performed in 17 patients and
      in three few days after. The late complications of the injury was urethral
      vaginal fistula in two, one vesicovaginal communication and one ureterovaginal,
      one stone formation and one transurethral catheter retention. The more affected
      organ was the bladder in 18 cases, urether and urethra. The injury to the
      inferior urinary tract represents 4.15% of the urogynecologic surgical
      complications, and 0.67% of the gynecological ones. The main aspect in the
      prognosis of the injury to the inferior urinary tract, is the early diagnostic
      during the surgical procedures.

PMID- 8549923
TI  - [Medical evaluation of the climacteric patient].
AB  - A pilot program with primary care physicians was established in Clinica
      Cuauhtemoc y Famosa, focused to evaluate women older than 35 years with
      climateric symptoms. This program included a survey, a complete gynecological
      examination with Pap smears, ultrasound pelvic examination and mamography. Also,
      blood samples were collected for cholesterol, tryglycerides, calcium, phosphorus
      and alkaline phosphatase. An ECG, bone densitometry of the radius and X-rays of
      the vertebral column were obtained. This group was formed by 69 women with an age
      media of 50 years (SD 7.6 years, median 49 years). The survey disclosed that
      34/65 women had been hysterectomized, and only 34/64 had received antitetanic
      immunization in the last 10 years. A preexistent chronic disease occurred in
      36/59 women, these were diabetes mellitus, arterial hypertension or degenerative
      osteoarthritis. Alcohol consumption was recorded in 5/66 women and tabac
      consumption in 9/66 women, and 32/68 women accepted to be sedentary. Laboratory
      examinations disclosed hypercholesterolemia in 19/66 women and
      hypertryglyceridemia in 8/64 women. Osteopenia was detected in 33/60 women. This
      findings support a systematic plan to provide medical assistance for women in
      this age, specially if previous epidemiologycal studies have disclosed that
      coronary disease is the main cause of death for women older than 50 years in this
      region, that also belongs to the area of highest incidence of diabetes.

PMID- 8549924
TI  - [Persistent trophoblastic tumor. Report of 15 cases at the National Institute of
      Perinatal Medicine].
AB  - Fifteen (18%) out of 83 patients with gestational trophoblastic disease,
      developed persistent trophoblastic tumor, from January, 1988 to March, 1994.
      Average age of patient was 25.5. There was antecedent of molar pregnancy in two
      cases. Beta fraction of chorionic gonadotrophin hormone at the time of diagnosis
      was 152,200 m UI/ml, average. During control it was in 80% of anovulatory oral
      cases. The treatment was based on metotrexate, and folinic acid; there was 100%
      remission. There was a total of 46.6% of pregnancies, after treatment; and 40% of
      them were normal.

PMID- 8549925
TI  - [Association of Chlamydia trachomatis and human papilloma virus as predisposing
      factors in cervical intraepithelial neoplasia].
AB  - Human papilloma virus (HPV) has a predisposing association as cofactor in
      etiopathology of cervicouterine cancer; it is known also that viral infection is
      not enough, and there are other agents, as Chlamydia trachomatis. The objective
      of this study was to investigate the association of these cofactors as
      predisposal for intraepithelial cervical neoplasia (NIC). Prospectively, at
      Clinica de Colposcopia, Hospital de Ginecologia y Obstetricia "Luis Castelazo
      Ayala", IMSS, 37 patients with cytologic, colposcopic and histological diagnosis
      of CIN pure or associated to HPV, underwent endocervical cytologies, and by
      immunofluorescence method, using monoclonal antibodies of conjugated
      fluoresceine, it was tried to demonstrate Chlamydia trachomatis, presence. From
      all patients, 12(32,4) were positive for Chlamydia trachomatis, significant
      percentually, and with Xi square of 0.32, non significant for this group of
      population. It is concluded that there is an important association of Chlamydia
      trachomatis and HPV, which should be taken into consideration in diagnosis and
      treatment of intraepithelial cervical neoplasia.

PMID- 8549926
TI  - [Male sterility and its association with genital disease and environmental
      factors].
AB  - Semen quality may be affected by many factors, as there is evidence that
      conditions as varicocele, criptorquidia, orchitis and bacterian infections; as
      well as to exposure to physical agents as heat, or chemical substances, or
      ingestion of alcohol and drugs, may affect semen quality. The objective of this
      study is to investigate the risk implied in the exposure to these factors on the
      semen quality. The study was carried out in a prospective way in a group of males
      at Clinica de Infertilidad, Unidad de Biologia de la Reproduccion del Hospital
      Universitario Dr. J.E. Gonzalez. Ninety nine males were studied, they received an
      intentioned questionnaire about antecedents of exposure to environmental factors,
      and urologic resolved pathology. Espermatobioscopy was done and it was classified
      according to OMS. Two groups were formed, one with the individuals with normal
      espermatobioscopy (n = 25); and the abnormal ones (n = 74). The statistical
      Incidences Reason, square Xi and Atributable Risk, were applied in order to
      determine the impact that different factors may have on semen quality. The found
      alterations in semen were astenozoospermia (n = 58); hypospermia (n = 22);
      oligozoospermia (n = 18); teratozoospermia (n = 7); polizoospermia (n = 7); and
      azoospermia (n = 6). The results of the mentioned statistical tests, show that in
      these alterations there is an associated risk factor to the use of tobacco,
      exposure to chemical substances, to physical aggresors; and anatomic anomalies
      previously corrected. It is considered that obtention of this information is a
      great help because once the unfavorable factors are eliminated, the environment
      is improved in order to obtain an espermatogenesis in optimal conditions.

PMID- 8549927
TI  - [Factors possibly associated with the age at the onset of menopause. Multicenter
      study].
AB  - A transversal study was performed in 1987 to examine 9,844 postmenopausal women
      aging from 39 to 59 years, residents from the cities of Durango, Monterrey,
      Guadalajara and Leon. They had their last menstruation at least 12 months before
      the interview and they were not pregnant. The objective was to know if the
      menarche, number of deliveries, use of contraceptive methods and smoking could
      affect the age of menopause. A case control analysis was performed. Based on
      frequency distribution of the age on which the menopause appeared, cases were
      classified as early and late menopause when a median value minus 2 SD and plus 2
      SD were found, respectively. For control subjects a median + 1 SD was selected.
      Two and three controls were randomly assigned for early and late menopause,
      respectively. In total 1,610 subjects were studied. As a measure of association
      it was used the odds ratio with a confidence level of 95%. It was performed an
      analysis of confusion and interaction of variables in this study. The most
      relevant results were; a significant association between smoking 15 packages of
      cigarettes a year with an OR of 2.31 (1.05-5.17), to have more than five
      pregnancies with an OR of Mantel and Haenzel of 0.51 (0.33-0.76) for the early
      menopause. No association with late menopause was observed. It was found that the
      mean age of menopause was 45.5 years + 4.5 SD (n = 9,844).

PMID- 8549928
TI  - [Human papillomavirus infection in male genitalia].
AB  - A prospective and transversal study in 100 patients since January to December of
      1994, was done, to know the human papiloma virus infection prevalence in male
      genitals. The patients were studied by a clinical history, genital area
      colposcopic revision after acetic acid 5% application, biopsy of the lesion and
      histopathology study. The patients age was among 16 to 71 years old, with a media
      of 38.8 years old. The sexual activity beginning was from 12 to 27 years old,
      with an average of 18 years old. Forty one percent of the patients have had
      sexual relations with prostitutes, 26% have had sexually transmitted diseases, 9%
      of the patients referred only 1 sexual mate and 82% had human papiloma virus
      infection.

PMID- 8549929
TI  - Metal stents in the oesophagus.

PMID- 8549930
TI  - Peptides and gastrointestinal mucosal integrity.

PMID- 8549931
TI  - Endocytosis of fluorescent microspheres by human oesophageal epithelial cells:
      comparison between normal and inflamed tissue.
AB  - This paper examines the presence and characteristics of endocytosis by
      oesophageal epithelial cells. Biopsy specimens from normal and inflamed
      oesophagus were incubated in organ culture with fluorescent microspheres (0.1 and
      0.01 microns diameter). These markers were taken into early endosomes and the
      lysosomes of both the smaller differentiating prickle cells and the larger mature
      squamous cells. Confocal and electron microscopy showed that markers passed to
      the early endosomes and the lysosomes by endocytosis. The process was energy
      dependent. Larger, 1 micron microspheres adhered to the epithelial cells but were
      not phagocytosed. Disaggregated cells were analysed by flow cytometry.
      Microspheres were endocytosed in proportion to the concentration in the culture
      medium in a dose dependent manner. Cells from inflamed oesophagus were
      significantly smaller (p = 0.013) and took up significantly more microspheres
      than cells from normal biopsy specimens (p = 0.015). In conclusion, endocytosis
      occurs in oesophageal epithelial cells and is increased in inflammation.

PMID- 8549933
TI  - Basic fibroblast growth factor treatment for non-steroidal anti-inflammatory drug
      associated gastric ulceration.
AB  - An open, pilot study tested the safety and efficacy of an acid stable form of the
      angiogenic protein basic fibroblast growth factor (bFGF) for healing of non
      steroidal anti-inflammatory drug (NSAID) associated gastric ulcers in five
      patients with nine gastric ulcers that were resistant to conventional treatment
      (4) or had relapsed (5). Oral bFGF treatment for four weeks was safe and well
      tolerated. There was no evidence of systemic absorption. After four weeks, four
      ulcers had healed and there was a 89 (3)% mean (SEM) reduction in the area of the
      others. A controlled, comparative trial of this novel growth factor treatment is
      warranted.

PMID- 8549932
TI  - Oesophageal sensation assessed by electrical stimuli and brain evoked potentials-
      a new model for visceral nociception.
AB  - Sensory thresholds and brain evoked potentials were determined in 12 healthy
      volunteers using electrical stimulation of the oesophagus 28 and 38 cm from the
      nares. The peaks of the evoked potentials were designated N for negative
      deflections and P for positive. Continuous electrical stimulation (40 Hz) at the
      38 cm position resembled heartburn (five of 12 subjects) while non-specific
      ('electrical') sensations were provoked at 28 cm (10 of 12). Thresholds of
      sensation and of pain were lower at the initial than the second determination,
      but did not differ with respect to stimulation site. The pain summation threshold
      to repeated stimuli (2 Hz, 5 stimuli) was determined for the first time in a
      viscus. This threshold was lower than the pain threshold to single stimuli at 38
      cm (p < 0.02). Evoked potential latencies did not change significantly over a six
      month period while the N1/P2 amplitude was higher at the first measurement (p <
      0.05). P1 and N1 latencies were significantly shorter 38 cm (medians 100 and 141
      ms) than 28 cm from the nares (102 and 148 ms) (p = 0.04 and p = 0.008).
      Electrical stimulation of the oesophagus may serve as a human experimental model
      for visceral pain. Longer evoked potential latencies from the proximal compared
      with distal stimulations provide new information about the sensory pathways of
      the oesophagus.

PMID- 8549934
TI  - Corticosteroids reduce regenerative repair of epithelium in experimental gastric
      ulcers.
AB  - The association between corticosteroid treatment and gastric ulcer healing is
      controversial. The effects of corticosteroids on experimental ulcer healing in
      the rat were studied and the effect of coadministration of a prostaglandin E1
      analogue was determined. Forty male adult rats were divided into five groups and
      pretreated for 10 days as follows: (a) control, (b) prednisolone (10 mg/kg), (c)
      prednisolone and misoprostol (300 micrograms/kg), (d) misoprostol, and (e)
      indomethacin (2 mg/kg) Gastric ulcer was induced by applying a cryoprobe to the
      serosal surface of the stomach. Healing was assessed by determining the ulcer
      size at three and six days. Mucosal regenerative activity at the ulcer edge was
      assessed by quantitating DNA synthesis in cells by immunohistochemical techniques
      using monoclonal antibodies to detect expression of proliferating cell nuclear
      antigen (PCNA) and incorporated 5-bromo-5-iododeoxyuridine (BrdU). Compared with
      control rats, the rate of healing and the mucosal regenerative activity were
      significantly reduced in rats treated with prednisolone and indomethacin (p <
      0.05). Coadministration of misoprostol and corticosteroids reversed the delay in
      healing and the reduction in mucosal regeneration induced by corticosteroids
      alone. With misoprostol alone, the ulcer size and the number of epithelial cells
      that actively synthesised DNA did not differ from control animals. A comparison
      between the two immunohistochemical markers of cell proliferation showed a highly
      significant correlation between the two techniques (r = 0.64, p < 0.005),
      indicating that the simpler PCNA technique should prove valuable in assessing
      regeneration in experimental ulcer disease.

PMID- 8549935
TI  - Mortality after remote surgery for benign gastroduodenal disease.
AB  - Mortality was studied after partial gastrectomy in a cohort of 1575 patients
      operated on because of benign gastroduodenal disease 29 to 59 years ago. The
      final status was confirmed in all but 8.4% of the cohort. At the close of the
      study 78% of the traced population were dead. Overall mortality was significantly
      higher than in the general population of southern Sweden (standardised mortality
      ratio = 1.10; 95% confidence intervals 1.03 to 1.17). Excess deaths resulted from
      neoplasms in the stomach, pancreas, male genital organs, and respiratory organs,
      as well as from respiratory diseases and suicide. Patients operated on before the
      age of 45 had a 60% increase in overall mortality during the first 19 years after
      surgery, mainly because of cardiovascular disease and suicide, whereas among
      those operated on after this age mortality was comparable to that in the
      reference population. The 75% increased death rate in cardiovascular disease
      during the first 19 years after surgery in patients operated on at young age,
      dramatically decreased during the years thereafter. An increased risk of death
      caused by malignancy was apparent more than 20 years postoperatively,
      irrespective of age at surgery. Excess deaths resulting from gastrointestinal
      malignancies, mainly gastric and pancreatic carcinoma, outnumbered the increased
      number of deaths resulting from cancer in the respiratory organs.

PMID- 8549936
TI  - Intestinal absorptive capacity, intestinal permeability and jejunal histology in
      HIV and their relation to diarrhoea.
AB  - Intestinal function is poorly defined in patients with HIV infection. Absorptive
      capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D
      xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings
      were correlated with the degree of immunosuppression (CD4 counts), diarrhoea,
      wasting, intestinal pathogen status, and histomorphometric analysis of jejunal
      biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent
      in all groups of patients with AIDS but not in asymptomatic, well patients with
      HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the
      degree of immune suppression and with body mass index. Increased intestinal
      permeability was found in all subgroups of patients. The changes in absorption
      permeability were of comparable severity to those found in patients with
      untreated coeliac disease. Jejunal histology, however, showed only mild changes
      in the villus height/crypt depth ratio as compared with subtotal villus atrophy
      in coeliac disease. Malabsorption and increased intestinal permeability are
      common in AIDS patients. Malabsorption, which has nutritional implications,
      relates more to immune suppression than jejunal morphological changes.

PMID- 8549937
TI  - Administration of insulin-like growth factor-I (IGF-I) peptides for three days
      stimulates proliferation of the small intestinal epithelium in rats.
AB  - It has previously been shown that longterm administration of insulin-like growth
      factor-I (IGF-I) or the analogue Long R3 IGF-I (LR3IGF-I) selectively stimulate
      growth of the gastrointestinal tract in gut resected, dexamethasone treated, and
      normal rats. In this study, the short-term effects of IGF-I administration on
      intestinal proliferation have been investigated. Female rats (110 g, five
      six/group) were infused for three days with 2.5 mg/kg/day of either IGF-I or
      LR3IGF-I and compared with vehicle treated or untreated control rats. LR3IGF-I
      but not IGF-I increased body weight and wet tissue weight of the small and large
      intestine (+20%), compared with controls. Tissue weight responses were
      independent of food intake and were reflected in the histology of the tissue. In
      LR3IGF-I treated animals, duodenal and ileal crypts length were increased by 13
      and 22%, respectively, associated with an increase in crypt cell number. No such
      histological changes were seen in IGF-I treated rats. Tritiated thymidine
      labelling indices were significantly increased after administration of either IGF
      I or LR3IGF-I (up to 14%) in both the duodenum and ileum. In IGF-I treated rats,
      increased nuclear labelling was not associated with an increase in the crypt
      compartment. In contrast, LR3IGF-I induced proportional increments in thymidine
      labelling and crypt size, suggesting that LR3IGF-I is not only more potent than
      the native peptide but also induced proliferative events more rapidly. In the
      colon, the thymidine labelling index was low, however, a non-significant increase
      in the number of cells labelled with thymidine was seen. These results suggest
      that within a three day treatment period intestinal mitogenesis is more advanced
      in animals treated with LR3IGF-I. The differences in proliferative response
      between the two peptides may be accounted for by variations in pharmacokinetics,
      clearance rates, and interactions with circulating and tissue specific binding
      proteins.

PMID- 8549938
TI  - Coeliac disease and bone mineral density in adult female patients.
AB  - A cross sectional study was undertaken to examine the relationship between
      coeliac disease and bone mineral density. The 135 female coeliac patients
      registered on the database of the Department of Gastroenterology at Hull Royal
      Infirmary were approached by letter, advising them of a potential risk of
      osteoporosis and inviting them to undergo bone densitometry. A total of 81
      registered women (60%) attended the Osteoporosis Laboratory, Princess Royal
      Hospital and underwent dual energy x ray absorptiometry at the lumbar spine (L2
      L4) and femoral neck. Historical data relating to the time of diagnosis and
      adherence to a gluten free diet were obtained. A control group was selected from
      the local normal population and was first matched for height, weight, and
      menopausal status. Postmenopausal patients were then further matched to controls
      of equivalent menopausal age. In coeliac patients, bone mineral density expressed
      in g/cm2 as mean (SD) was significantly lower at the lumbar spine (1.076 (0.186))
      than in the control group (1.155 (0.143), p < 0.001). This was also the case at
      the femoral neck (0.887 (0.142) versus 0.965 (0.127), p < 0.001). When the
      coeliac patients were stratified by menopausal status, it was found that femoral
      neck bone mineral density was significantly below control values in both
      premenopausal and postmenopausal women. Spinal bone mineral density exhibited a
      significant decrement only in the postmenopausal group. The age at diagnosis of
      coeliac disease and adherence to a gluten free diet did not influence bone
      mineral density at either hip or spine. These results confirm coeliac patients'
      higher risk of osteopenia. Coeliac disease should be added to the list of medical
      conditions which constitute an indication for bone densitometry in order that the
      individual risk of osteoporosis related fracture may be determined.

PMID- 8549939
TI  - Evaluation of antral motility in humans using manometry and scintigraphy.
AB  - Recent studies suggest that scintigraphy can be used to evaluate non-invasively
      antral motility in humans, although scintigraphic techniques have not yet been
      compared with more conventional measurements of intraluminal pressures by
      manometry. Simultaneous scintigraphic and manometric measurements of antral
      motility were performed in nine healthy volunteers. After intubation with a
      sleeve/sidehole catheter which incorporated five pressure sideholes located at
      1.5 cm intervals spanning the antrum, each subject ingested 100 g minced beef
      labelled with 100 MBq 99mTc-chicken liver and 150 ml water. Between 40-43, 60-63,
      80-83, and 100-103 minutes after meal ingestion, radioisotopic data were acquired
      in two second frames. Time-activity curves showing antral 'contractions'
      resulting from wall motion were derived by drawing small regions of interest over
      the antrum to coincide with the position of the antral manometric sideholes.
      Scintigraphic contraction rates approximated 3/minute, whereas antral pressure
      waves that occluded the lumen were less frequent (p < 0.01 for all), particularly
      in the proximal antrum. The amplitude of wall motion, evaluated
      scintigraphically, and the amplitude of pressure waves were both inversely
      related to the distance from the pylorus (r > -0.32, p < 0.05) and antral volume
      r > -0.29 (p < 0.05). There were significant relationships between the amplitude
      of contractions assessed scintigraphically and the number of lumen-occlusive
      antral pressure waves in the distal antrum (r -0.48, p < 0.05) but not in the
      more proximal antral regions. It is concluded that scintigraphy can detect antral
      wall motion with greater sensitivity than manometry, particularly in the proximal
      antrum. As manometry gives information on the amplitude as well as the temporal
      and spatial organisation of those contractions which result in lumen occlusion,
      the combination of scintigraphic and manometric techniques in the evaluation of
      antral motility shows considerable promise.

PMID- 8549940
TI  - Motor activity recorded in the unprepared colon of healthy humans.
AB  - A manometric method was developed to study the motor activity in the unprepared
      human colon, and the results in eight healthy subjects were compared with those
      obtained in the same subjects after bowel cleansing with a non-absorbable
      solution containing polyethylene glycol 4000 (PEG). A tube assembly (4.5 m long,
      12 lumen) was introduced through the nose and passed through the gastrointestinal
      tract. Two manometric recordings were performed one month apart, one without any
      preparation and the other after bowel cleansing with PEG. There was no obvious
      qualitative difference between the recordings performed in the uncleansed and PEG
      cleansed colon. Moreover, in the unprepared colon motility indices were close to
      those measured in the cleansed colon. The number of high amplitude propagated
      contractions (mean (SEM)) was, however, higher in the cleansed colon (8.6 (2.8) v
      5.4 (1.8)/subject/9 h in the unprepared colon; p < 0.04). It is concluded that in
      healthy subjects taking a regular diet, motor activity is not different between
      the uncleansed and cleansed colon with PEG, except for the high amplitude
      propagated contractions, which occur more frequently in the cleansed colon.

PMID- 8549941
TI  - Effects of simvastatin and cholestyramine on bile lipid composition and gall
      bladder motility in patients with hypercholesterolaemia.
AB  - Although the effects of 3-hydroxy, 3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors and bile acid sequestrants on bile lipid composition have
      been studied separately, no data are available on combination therapy of these
      drugs. Moreover, the effects of prolonged (four weeks) administration of these
      drugs on gall bladder motility, an important determinant of cholesterol gall
      stone formation, have not been studied so far. A prospective study was therefore
      performed with eight patients who had hypercholesterolaemia (age 53 (5) (SEM),
      body mass index 27.4 (1.1) kg m-2, low density lipoprotein cholesterol 5.9 (0.3)
      mmol/l). They received treatment during three periods of four weeks with
      simvastatin 20 mg/day, cholestyramine 4 g twice daily, and a combination of both
      in random order, each treatment period separated by a two week wash out period.
      Before treatment and after each treatment period, postprandial gall bladder
      motility was studied with ultrasound, followed by duodenal bile sampling. Serum
      cholesterol decreased in all subjects in any treatment period illustrating good
      compliance. Molar percentages in duodenal bile of cholesterol, phospholipids, and
      bile salts were unchanged during simvastatin and cholestyramine treatment. During
      combined therapy percentage bile salts was lower (72.5 (2.9)% v 77.8 (1.7)% at
      baseline, p < 0.05) whereas phospholipids were higher (21.2 (2.4)% v 16.4 (1.3)%
      at baseline, p < 0.05). As a result cholesterol saturation index (CSI) did not
      change in any treatment period. No cholesterol crystals were detected in any bile
      sample, taken at baseline and after each treatment period. Bile salt
      hydrophobicity index during cholestyramine (0.19 (0.02)) and combined treatment
      (0.22 (0.01)) decreased strongly compared with baseline (0.34 (0.01), p < 0.001,
      p < 0.01, respectively), resulting from increased proportions of glycocholate
      (59.4 (3.9)% (cholestyramine), 55.6 (2.4)% (combination), and 28.2 (2.2)
      (baseline), p < 0.001)) and decreased proportions of deoxycholic acid and
      chenodeoxycholic acid. Fasting gall bladder volume was increased during
      simvastatin (28.7 (2.8) ml) v baseline (23.2 (2.3) ml, p < 0.01) whereas,
      residual volume did not differ (5.7 (0.9) ml (simvastatin) v 5.9 (0.7)
      (baseline). During cholestyramine and combined treatment, no significant
      differences in gall bladder motility were seen. In conclusion, this study
      suggests that HMG-CoA reductase inhibitors alone and combined with cholestyramine
      do not affect major determinants of cholesterol gall stone formation, for
      example, CSI and gall bladder emptying. In addition cholestyramine alone and
      combined with simvastatin leads to a strong decrease of bile salt hydrophobicity,
      which may be beneficial in the prevention of nucleation of cholesterol crystals.

PMID- 8549942
TI  - Mycobacterium paratuberculosis DNA not detected in Crohn's disease tissue by
      fluorescent polymerase chain reaction.
AB  - The role of mycobacteria in the aetiology of Crohn's disease has been a
      contentious subject for many years. Mycobacterium paratuberculosis is known to
      cause a chronic granulomatous enteritis in animals (Johne's disease) and has been
      implicated as a possible infectious cause of Crohn's disease. However this
      fastidious organism is only rarely detected by conventional microbiological
      techniques. This study used oligonucleotide primers to the species-specific M
      paratuberculosis IS900 DNA insertion element and the polymerase chain reaction to
      amplify any M paratuberculosis DNA from intestinal tissue DNA extracts. One
      oligonucleotide primer was fluorochrome-labelled and the presence of fluorescent
      amplified product was determined using an automated DNA sequencer with a
      computerised gel-scanning laser. This method was shown capable of detecting 1-2
      mycobacterial genomes. Intestinal tissue samples were obtained from 68 patients
      with histologically confirmed Crohn's disease, 49 patients with histologically
      confirmed ulcerative colitis, and 26 non-inflammatory bowel disease controls. In
      no case was M paratuberculosis detected in any of the inflammatory bowel disease
      tissue samples and only one non-inflammatory bowel disease case was positive.
      These results do not support the hypothesis that M paratuberculosis has an
      aetiological role in Crohn's disease.

PMID- 8549944
TI  - A controlled double blind study of azathioprine in the management of Crohn's
      disease.
AB  - While immunosuppressive agents are used widely in the management of Crohn's
      disease, their efficacy has not been well established in randomised controlled
      trials. This study was designed to examine whether azathioprine increases
      remission rate when used in conjunction with a diminishing dose regimen of
      prednisolone over a period of 12 weeks. It further examined whether azathioprine
      offers any therapeutic advantage over placebo in the maintenance of remission in
      Crohn's disease over a period of 15 months. Sixty three patients with active
      Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and
      at the same time entered into a randomised, double blind 15 month trial of either
      azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were
      compared at 12 weeks and at 15 months. There was no significant difference in the
      proportion of patients who had achieved and maintained remission by week 12 but
      at 15 months there was a highly significant difference in the proportion of
      patients in remission (42% receiving azathioprine v 7% receiving placebo), p =
      0.001. Using life tables this beneficial effect was reflected as the difference
      in the median number of days on the trial (p = 0.02). There were significantly
      greater decreases over the trial period in the median erythrocyte sedimentation
      rate, C reactive protein, and leucocyte count in the azathioprine group. There
      were no cases of severe bone marrow suppression or clinical pancreatitis. In
      conclusion, azathioprine offers a therapeutic advantage over placebo in the
      maintenance of remission in Crohn's disease.

PMID- 8549943
TI  - Meta-analysis of the role of oral contraceptive agents in inflammatory bowel
      disease.
AB  - Numerous epidemiological studies have been performed to determine factors that
      might contribute to the development of inflammatory bowel disease. Although the
      role of oral contraceptive agents in Crohn's disease (CD) and ulcerative colitis
      (UC) have been assessed, most studies were of small sample size and characterised
      by low statistical precision. A meta-analysis was performed to increase the
      statistical power and to investigate the association between the use of oral
      contraceptives and the development of CD and UC. The study was based on a search
      of a Medline database from 1975 to October 1993 and a review of reference lists
      from published articles, reviews, symposia proceedings, and abstracts from major
      gastrointestinal meetings. All studies specifically designed to evaluate this
      association were selected. The combined results of nine studies--two cohort
      studies (30,379 unexposed and 30,673 exposed patients) and seven case-control
      studies (482 CD, 237 UC, and 3198 controls)--which satisfied our selection
      criteria were evaluated. The pooled relative risk (adjusted for smoking)
      associated with oral contraceptive use was 1.44 (1.12, 1.86) for CD and 1.29
      (0.94, 1.77) for UC. These results suggest modest associations between the use of
      oral contraceptives and the development of CD and UC. As these associations are
      weak, non-causal explanations for the findings cannot be eliminated.

PMID- 8549945
TI  - Quantitative assessment of overall inflammatory bowel disease activity using
      labelled leucocytes: a direct comparison between indium-111 and technetium-99m
      HMPAO methods.
AB  - The ideal imaging method in inflammatory bowel disease would reliably detect
      inflammation, identify the correct intestinal location, and assess the severity
      of the disease. The aim of this study was to compare scintigraphic methods of
      quantifying overall disease activity using both indium-111 (111In) and technetium
      99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of
      111In was measured after 111In scintigraphy in 24 patients known to have
      inflammatory bowel disease. The same patients also underwent 99mTc HMPAO
      scanning. The scans were performed 10 days or less apart with no changes in
      treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed
      using a computer based method (scan score) and a visual grading method in a
      further 54 99mTc HMPAO. The results showed a close correlation between
      inflammatory activity defined by faecal 111In excretion and the scan score
      generated from the computer analysis of the 99mTc HMPAO image (Spearman rank
      correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory
      activity could be obtained by simple visual assessment of both types of scan
      images, although image quality was superior with 99mTc HMPAO. Qualification of
      disease activity from 99mTc HMPAO images by visual grading was associated with a
      large variability, only 69% of scans had similar scores when graded by three
      observers. Computer generated image analysis was more reproducible. In
      conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal
      111In excretion correlated well. Either method can quantify and localise the
      inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower
      radiation dose, and avoids faecal collection, it may be the preferred method.

PMID- 8549946
TI  - Kinetic studies on colonocyte metabolism of short chain fatty acids and glucose
      in ulcerative colitis.
AB  - Short chain fatty acids (SCFAs) are potentially valuable as a topical therapy for
      distal ulcerative colitis. The mechanism of action is unknown but may involve
      improved intracellular energy production as previous evidence indicates that
      colonocyte oxidation of butyrate is impaired in ulcerative colitis. No
      information is, however, available on human mucosal metabolism of acetate and
      propionate in either health or disease or the Vmax and Km values of butyrate
      oxidation. The aim of the study was to assess the kinetic parameters, Vmax and
      Km, of the complete oxidation of short chain fatty acids and glucose by human
      colonocytes and to explore whether a metabolic abnormality could be confirmed in
      patients with ulcerative colitis. Colonocytes were isolated from surgical
      specimens obtained from 14 patients with ulcerative colitis and eight control
      subjects. Incubations were performed in the presence of a concentration range of
      14C-labelled acetate, propionate butyrate, and glucose. Oxidation rates were
      obtained by quantifying the production of 14CO2. Vmax and Km were calculated by
      computer fitting of the data to a Michaelis-Menten plot. No significant
      differences were shown in either Vmax or Km values of any of the SCFAs or glucose
      comparing controls and patients with ulcerative colitis. Comparing the results
      obtained regarding the individual SCFAs, the most striking difference was the
      considerably lower Km value of butyrate. The apparent Vmax of acetate tended to
      be higher than Vmax of propionate and butyrate. Vmax of glucose oxidation was
      significantly lower compared with the Vmax values of SCFA oxidation. The study
      shows the ability of isolated human colonocytes to utilise each of the three
      major SCFAs, but does not support a pathogenic role for defective metabolism of
      butyrate in ulcerative colitis. The considerably lower Km of butyrate oxidation
      supports a specific role of butyrate as an energy source for the colonic mucosa
      in both health and ulcerative colitis.

PMID- 8549947
TI  - Transglutaminases in Crohn's disease.
AB  - Transglutaminases are a family of Ca-dependent enzymes involved in various
      biological events. Circulating transglutaminase (factor XIIIa) is decreased in
      blood of patients with inflammatory bowel diseases. There is evidence that factor
      XIIIa and tissue type transglutaminase, present in cell cytosol, bind to various
      proteins of the extracellular matrix. This study examined the value of serum
      transglutaminase assay in the treatment and follow up of Crohn's disease and then
      investigated the intestinal location of both forms of transglutaminases by
      immunohistochemistry in normal and abnormal tissues. Serum transglutaminase
      activity was assayed in 36 patients with active Crohn's disease (CDAI > 150).
      Eighteen patients were studied prospectively from relapse into remission. A
      significant inverse correlation (p < 0.001) was found between circulating
      transglutaminase and Crohn's disease activity index; a correlation was also found
      between serum transglutaminase and serum orosomucoid (p < 0.01) and C reactive
      protein (p < 0.01). Patients were prospectively studied until clinical remission
      showed improvement in both their CDAI score mean (SD) (230 (46) to 72 (34), p <
      0.01) and transglutaminase activity mean (SD) (0.61 (0.12) to 0.93 (0.13) mU/ml,
      p < 0.01). The immunohistochemistry assessment showed a colocalisation of factor
      XIIIa and tissue transglutaminase to the extracellular matrix of damaged tissues.
      In conclusion, these data confirm the value of serum transglutaminase assay as
      marker of Crohn's disease activity, extend the utility of serum transglutaminase
      assay to follow up of the disease, and emphasised the role of different types of
      transglutaminases in extracellular matrix assembly in the damaged tissues.

PMID- 8549948
TI  - Clinical course of perianal fistulas in Crohn's disease.
AB  - The clinical course of perianal fistulas and associated abscesses was evaluated
      prospectively in 90 patients with Crohn's disease. Fistula type, rectal disease,
      faecal diversion, and immunosuppression were examined as prognostic indicators
      for fistula healing and recurrence. Median follow up was 22 months. The outcome
      was evaluated with life table analysis. Prognostic factors were analysed by
      multiple regression. Inactivation was achieved in all patients. The risks of
      recurrent fistula activity were 48% at one year and 59% at two years. Fistulas
      were healed in 51% after two years but reopened in 44% within 18 months of
      healing. Faecal diversion and absence of rectal disease decreased recurrence
      rates (p = 0.019/0.04) and increased healing rates (p = 0.005/0.017). The outcome
      in patients with trans-sphincteric fistulas was better than that in those with
      ischiorectal fistulas but worse than in patients with subcutaneous fistulas (p =
      0.015 for healing; p = 0.007 for recurrent fistula activity). After initial
      treatment about 20% of the patients were symptomatic and about 10% had painful
      events per six month period. Incontinence was rare and did not increase during
      the study period. Perianal fistulas and associated abscesses can be controlled
      safely by simple drainage of pus collections. Frequent reinfection and re-opening
      after healing of fistulas are characteristic. Fistula type, rectal disease, and
      stool contamination influence the clinical course. Only a few patients, however,
      have continuous symptoms from perianal fistulas.

PMID- 8549949
TI  - Oral efficacy of a leukotriene B4 receptor antagonist in colitic cotton-top
      tamarins.
AB  - Leukotriene B4 (LTB4) is a potent neutrophil activator and chemotaxin that is
      present in increased concentrations in the colonic tissue and rectal dialysates
      of acute ulcerative colitis patients. Cotton-top tamarins (CTTs) with confirmed
      active colitis were treated with the second generation LTB4 receptor antagonist,
      SC-53228 ((+)-(S)-7-[3-(2-cyclopropyl-methyl)-3-methoxy-4-[(methylamino)
      carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2- propanoic
      acid), 20 mg/kg bodyweight by gavage, twice daily for 56 days. End points were
      body weights, stool consistency, colonic endoscopy, assay of inflammatory
      mediators, and haematology and clinical chemistry tests. LTB4 and prostaglandin E
      (PGE) values were measured in rectal dialysates at pretreatment, 28 day and 56
      day time points. LTB4 concentrations were reduced from pretreatment mean (SEM)
      values of 37.3 (0.8) ng/ml to 3.7 (0.8) ng/ml (p < 0.001) and 2.3 (0.5) ng/ml (p
      < 0.01) at days 28 and 56, respectively. On the other hand, mucosal protective
      PGE values remained constant or slightly increased during SC-53228 treatment
      (pre: 6.9 (2.2) ng/ml; day 28: 6.7 (1.4) ng/ml; day 56: 9.9 (1.6) ng/ml).
      Furthermore, assessment of a panel of 35 clinical chemistry and haematology
      parameters throughout the treatment showed there were no significant untoward
      effects of drug treatment. Six CCTs finished the eight week treatment and five of
      six gained weight (ranging from 27-121 grams each) while one CTT lost weight (50
      g). Stool condition improved in five of six animals while one of six remained
      unchanged. All CCTs showed dramatic improvement histologically, with no or only
      minimally active colitis after treatment. The histological changes plus
      significant weight gains and improvement of stool condition (quality of life
      parameters) after eight weeks of SC-53228 treatment were remarkable. Furthermore,
      in follow up biopsies seven months after treatment ceased, three of six CTTs had
      no active colitis. This is the first time afflicted CTTs have not had recurring
      colitic exacerbations after a treatment regimen was stopped. It is concluded that
      in colitic CTTs, SC-53228 has shown both an immediate and a long acting
      anticolitic activity. It is also concluded that reduced LTB4 concentrations
      during treatment inhibited neutrophil infiltration of the colonic tissue and
      this, coupled with the maintenance of mucosal protective prostaglandins,
      contributed to the dramatic anticolitic efficacy. The treatment was safe over
      eight weeks. A compound such as SC-53228 may be useful in the medical treatment
      of human inflammatory bowel disease.

PMID- 8549950
TI  - Ranitidine, diarrhoea, and lymphocytic colitis.
AB  - A 69 year old woman developed chronic diarrhoea while being treated with
      ranitidine. Sigmoidoscopy was performed after six weeks and showed typical
      histological features of lymphocytic colitis. Ranitidine was withdrawn and the
      diarrhoea resolved. Eight months later, a 72 hour oral rechallenge period of
      ranitidine, was performed immediately preceded (period 1) and followed (period 2)
      by sigmoidoscopy and biopsy. Diarrhoea recurred during the rechallenge period and
      resolved again within one day after drug withdrawal. The mean (SEM)
      intraepithelial lymphocyte count was not significantly different between periods
      1 and 2 (11.9 (0.6) and 13.1 (0.4) per 100, respectively). An immunopathological
      study of 30 serial sections of biopsy specimens was performed for both periods 1
      and 2. The expression of HLA-DR by the rectal epithelium was mild or absent in
      all sections from period 1, and was considerable in 25 of 30 sections from period
      2 (p < 10(-9)). It is suggested that the oral intake of ranitidine was
      responsible for the diarrhoea and induced the immunopathological signs of
      activation of the rectal mucosal immune system during the rechallenge period.

PMID- 8549952
TI  - Efficacy of longterm interferon treatment in chronic liver disease evaluated by
      sensitive polymerase chain reaction assay for hepatitis C virus RNA.
AB  - Effects of interferon treatment on hepatitis C virus were examined by
      investigating the presence of hepatitis C virus ribonucleic acid and anti
      hepatitis C virus antibody in 70 patients with non-A, non-B chronic liver
      diseases. Twenty one patients were treated with three million units of interferon
      alfa 2a three times a week for 52 weeks, 24 patients were treated similarly for
      eight weeks, and 25 patients were given a placebo for eight weeks and served as
      control. Sixty six of 70 patients (94%) were positive for both hepatitis C virus
      RNA and second generation anti-hepatitis C virus antibody. Fourteen of 21 (67%)
      receiving the longterm treatment had a normalised alanine aminotransferase (ALT)
      activity, and in 12 of these hepatitis C virus ribonucleic acid became
      undetectable by the end of treatment and remained so during the three year follow
      up after the treatment. Anti-hepatitis C virus antibody determined by first
      generation assay became negative in one case at the end of the 52 week treatment,
      and in four cases at the end of the one year follow up. In contrast, only one of
      24 (4%) who received the eight week treatment and only one of 25 (4%) who
      received the placebo had normalised ALT activities. Hepatitis C virus ribonucleic
      acid became negative in two patients undergoing short-term treatment and in none
      receiving the placebo. Thus, longterm interferon treatment seems effective in
      clearing hepatitis C virus from serum of patients with chronic liver disease.

PMID- 8549951
TI  - Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of
      nm23-H1 expression in advanced tumour stages.
AB  - Although a reduced expression of nm23 has been shown to correlate with a high
      metastatic potential in some human cancers, in colorectal cancers, conflicting
      data have been reported. As there are two homologous genes, nm23-H1 and nm23-H2,
      which encode the A and B subunits of nucleoside diphosphate kinase, efficient and
      simplified techniques were designed to selectively study nm23-H1 and -H2
      expression in 35 colorectal cancers at both the protein and mRNA levels by
      immunoblotting, immunohistochemistry, and reverse transcription polymerase chain
      reaction (RT PCR) using specific antibodies and primers. Nm23-H1 and Nm23-H2
      proteins were overexpressed in tumours compared with adjacent mucosa. This
      overexpression was lost, however, in some advanced cases: 89% and 81% of TNM
      (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression,
      respectively, which significantly differed from 47% and 38% of stage III-IV
      tumours. Similar results were seen with nm23-H1 mRNA. Heterogenous labelling of
      tumoral cells was seen by immunohistological staining. This suggests a dichotomy:
      an overexpression of nm23-H1 and -H2 linked to early stages of cancer and a loss
      of nm23-H1 overexpression seen in more advanced stages. Therefore specific nm23
      H1 determination should be evaluated as a prognostic factor in human colorectal
      carcinoma.

PMID- 8549954
TI  - Linear IgA dermatosis, coeliac disease, and extraintestinal B cell lymphoma.
AB  - Linear IgA dermatosis is a malignancy associated rare bullous disorder similar to
      dermatitis herpetiformis. Linear IgA dermatosis differs from dermatitis
      herpetiformis in that the IgA deposits in the epidermal basement membrane are
      linear rather than granular. A patient is presented with coeliac disease who
      presented with linear IgA dermatosis and anaemia caused by chronic low grade B
      cell lymphoma.

PMID- 8549953
TI  - Hepatocellular carcinoma and African iron overload.
AB  - Both hepatocellular carcinoma (HCC) and iron overload are important health
      problems in Africa. Chronic hepatitis B virus (HBV) infection is recognised as a
      major risk factor for HCC, but iron overload in Africans has not been considered
      in pathogenesis. Up to half the patients with HCC in Africa do not have any
      recognised risk factors such as preceding chronic HBV infection, and other risk
      factors remain unidentified. HCC is an important complication of HLA-linked
      haemochromatosis, an iron loading disorder found in Europeans. It is proposed
      that African iron overload might also be a risk factor for HCC.

PMID- 8549955
TI  - Gastroenterological training in Europe.

PMID- 8549956
TI  - [Prophylactic inspiratory muscle training before coronary artery bypass graft].
AB  - Pulmonary complications after cardiac surgery are a leading cause of
      postoperative morbidity and mortality. Respiratory muscle weakness may contribute
      to the postoperative pulmonary abnormalities. We hypothesized that: inspiratory
      muscle strength (PImax at RV) and endurance (PmPeak/PImax) decrease following
      coronary artery bypass grafting (CABG); that this weakness is associated with
      impaired pulmonary function tests (PFT), impaired gas exchange and a higher rate
      of pulmonary complications; and that prophylactic inspiratory muscle training
      (PIMT) will prevent these changes. 30 candidates for CABG, ranging in age from 33
      to 79, were evaluated and randomized into 2 groups: 15 received PIMT using a
      threshold trainer for 30 min/day for 1 month before operation, while 15 served as
      controls and received sham training. There was a significant decrease in
      respiratory muscle function, PFT, and gas exchange in the control group following
      CABG, while in the trained group these parameters where similar to those before
      entering the study. The differences between the groups were statistically
      significant. In addition, 4 (27%) in the control group, but only 1 (7%) in the
      trained group had postoperative pulmonary complications. We conclude that CABG is
      followed by significant deterioration in inspiratory muscle function, PFT and
      arterial blood gases. Decrease in these parameters can be prevented by PIMT,
      which may also prevent postoperative pulmonary complications.

PMID- 8549957
TI  - [Serodiagnosis of atypical bacterial respiratory infections].
AB  - Since prevalence of antibodies to bacteria causing atypical respiratory
      infections in Israel is as yet unknown, a 5-year antibody prevalence study was
      performed. Seroreactivity to Chlamydia pneumoniae (TWAR), with titers > or = 1:16
      by microimmunofluorescence assay (MIF) was detected in 725/1305 (55.5%) of
      patients. 47/1012 ((4.6%) of adult patients had MIF results indicating recent
      infection with TWAR, (IgG titers of > or = 1:512, and/or IgM titers of > or =
      1:16, and/or seroconversion). Antibody prevalence and titers were low in children
      aged 1-10 years, increased in teenagers, and peaked in adults and the elderly, in
      whom prevalence was up to 79% and mean geometric titer up to 1:163. Unlike the
      consistency in TWAR antibody prevalence and serological evidence of recent
      infection during the study period, a significant decrease in those variables was
      observed for Chlamydia trachomatis during the first 3 study years. Antibodies to
      M. pneumoniae were detected in 53 and to Legionella sp. in 47 out of 763
      patients. There was serological evidence of recent infection with M. pneumoniae
      in 10 (including 7 children) and with Legionellae in 8. Improved diagnosis of
      atypical respiratory infection might be achieved by the combined use of these
      proposed serological procedures.

PMID- 8549958
TI  - [Systemic lupus erythematosus in children in Israel].
AB  - Systemic lupus erythematosus (SLE) is a rare disease in children that might
      possibly be modulated by genetic and environmental factors. In order to delineate
      the characteristic features of SLE among Israeli children, we reviewed the
      medical records of 38 cases from 8 pediatric rheumatology clinics. All fulfilled
      the 1982 American Rheumatism Association revised criteria for SLE. The illness
      became apparent at the age of 16 years or younger and the mean age of onset was
      11.9 +/- 2.4 y (range 7-16) and the mean duration of follow-up 4.0 +/- 4.8 y
      (range 0.5-15). The female to male ratio was 2.8:1; 28 were Jewish and 10 Arabs.
      Systemic complaints, such as fever, malaise and weight loss, were noted in 90%,
      malar rash in 65%, and other skin manifestations in 40%. Arthritis was noted in
      57% and additional musculoskeletal complaints in 70%; 90% had hematological
      abnormalities. Major organ system involvement included: renal disease in 50%
      pulmonary involvement 28% and CNS involvement 28%. 2 patients are currently on
      renal dialysis and 1 died from hypertensive crisis. We conclude that the features
      of SLE in children in Israel are not influenced by ethnic or geographic factors,
      and are similar to those reported worldwide.

PMID- 8549959
TI  - [Transanal endoscopic microsurgery for local excision of rectal neoplasms].
AB  - We removed 30 benign, sessile, rectal polyps by the transanal approach between
      January 1990 and April 1994. In 16 patients we used transanal endoscopic
      microsurgery (TEM), while in 14 the adenoma was removed by submucosal excision
      (SE). There were 3 local recurrences in the SE group, but none as yet in the TEM
      group. There was no operative mortality. Early complications included myocardial
      infarction in 1 patient and persistent postoperative fever which responded to
      antibiotic treatment in another. Late complications included temporary, anal
      mucous leakage in 10% and 5% of the TEM and SE groups, respectively. TEM was
      found to be efficient for the removal of polyps in the upper and middle thirds of
      the rectum, and SE for those in the lower third. This enables safe removal of
      rectal polyps, avoiding the need for complex operations involving greater risks.

PMID- 8549960
TI  - [Chronic otitis media].
AB  - Results of middle ear operations performed between 1984-1989 were analyzed. The
      operations included 139 simple mastoidectomies, 68 radical mastoidectomies, and
      41 simple mastoidectomies with tympanoplasty. 342 tympanoplasties were also
      performed, 51 in children up to 14 years old and 291 in those over 14. We
      conclude that the Schuller view and CT are not conclusive as to the presence of
      cholesteatoma, and cannot be relied on without other confirmation in planning the
      type of operation. Of patients with cholesteatoma who underwent simple
      mastoidectomy, in 21.1% the cholesteatoma recurred and revision or radical
      mastoidectomy was necessary. When the Eustachian tube was patent, the graft took
      in more than 90% of cases. Fibrin glue did not affect the results of
      tympanoplasty or myringoplasty. Graft take was similar in those under and over
      the age of 14. Tympanoplasty in children has a good chance of succeeding, and
      enables most to return to a normal life (including swimming).

PMID- 8549961
TI  - [Tuberculosis: a retrospective study].
AB  - In a retrospective study, 60 cases of tuberculosis (TB) were seen during 1968
      1977. 95% were either Jewish or Bedouin. About 25% of the Bedouin were under 20
      years of age. 62 of the cases had extra-pulmonary tuberculosis, while only 38%
      had the pulmonary form. As has been noted before, different ethnic groups had
      distinctive clinical features of tuberculosis. After a constant decline in the
      rate of tuberculosis in Israel for 4 decades, an increasing incidence has
      recently been observed. This trend is explained by waves of immigration from
      countries where tuberculosis is prevalent. The diagnosis was made quite late in
      the course of the disease, mainly because tuberculosis has been considered rare
      in Israel. A higher index of suspicion will allow earlier diagnosis and treatment
      of this curable disease.

PMID- 8549962
TI  - [All-terrain vehicle accidents].
AB  - All-terrain vehicles (ATV) are designed for off-the-road occupational or
      recreational use. As their popularity has been increasing steadily, information
      has been accumulating on the morbidity and mortality associated with their use.
      The attributes of the ATV that make it attractive for recreation and sport are
      the reasons for much of its danger. Thus, horsepower, speed and ability to travel
      on rough and uncertain terrain are causal factors for accidents. The poor
      judgment and risk-taking of many of the young and immature drivers contribute to
      the great danger. 61 admissions due to ATV accidents from October 1992 to April
      1995 are reviewed. The data suggest that ATV riders are at high risk for serious
      skeletal injuries and death. ATVs clearly present health hazards for riders of
      all ages, unless they are driven with great care. Guidelines for reducing the
      number and severity of injuries, such as age limits, safety programs and
      protective equipment are suggested.

PMID- 8549963
TI  - [Incidence of sports-related eye injuries].
AB  - The incidence of sports-related eye injuries was analyzed retrospectively for
      1991-1993. It was fairly steady at about 2% of all eye casualties annually. 21%
      of those with sports-related eye injuries required hospitalization. The commonest
      pathological findings were corneal erosion (32%), eye lid injuries (27%), hyphema
      (19%) and macular edema (3%). Most eyes were injured during soccer (37%) and
      basketball (27%) games, the most popular sports in Israel.

PMID- 8549964
TI  - [Uncommon manifestations of schistosomal colitis in African immigrants].
AB  - Schistosomiasis is rare in Israel but very common in Africa. The recent Ethiopian
      immigration has brought us cases of parasitic diseases unfamiliar to Israeli
      physicians. 3 cases with uncommon manifestations of colonic schistosomiasis are
      described. The first had bloody diarrhea for 4 years. The second had co-infection
      with Salmonella D. The third was diagnosed as having schistosomal colitis on
      routine sigmoidoscopy, which was performed following diagnosis of rectal
      carcinoma in her brother.

PMID- 8549966
TI  - [Atherosclerosis as an immune process].

PMID- 8549965
TI  - [Osteoradionecrosis of the jaws].
AB  - 9 patients with osteoradionecrosis of the mandible were treated during 1975-1994.
      All primary tumor had received high dose external radiation or brachytherapy,
      using iridium-192 sources. In 6 patients the complication was triggered, shortly
      before or after irradiation, by surgical interventions such as tooth extraction,
      or by the presence of an infected focus in the mandible. The complications were
      treated conservatively, including 2 cases by hyperbaric oxygen. The value of
      prevention is emphasized.

PMID- 8549968
TI  - [Pyridinium cross-links: sensitive markers of bone catabolism].

PMID- 8549967
TI  - [Molecular advances in ophthalmology--identifying the genes for retinitis
      pigmentosa].

PMID- 8549969
TI  - [Definition of pathological second stage in labor: theory and practice].

PMID- 8549970
TI  - [Identification of diabetic patients at high risk for development of
      retinopathy].

PMID- 8549971
TI  - [Role of breast milk feeding in avoidance of asthma and other allergic
      disorders].

PMID- 8549972
TI  - [Serum tumor markers in the diagnosis of cancer of unknown primary site].

PMID- 8549973
TI  - [Imaging of collateral venous systems in portal hypertension].

PMID- 8549974
TI  - [Sudden death in Turner's syndrome].

PMID- 8549975
TI  - [The general practitioner as physician of first contact with health problems].
AB  - An aim of this study was to determine the extent to which general practitioners
      (GPs) are their patients' physicians of first contact (PFCs) for specific health
      problems. It was also designed to explain the differences between physicians who
      treat these problems, and those who do not, by the type of problem presented, the
      characteristics of the physician, and the characteristics of the environment in
      which the physician works. The study is based on data collected in a nationwide
      mail survey in 1993 among 677 GPs working in 1 or more of Israel's 4 health
      insurance funds. They were asked if they were their patients' PFC for 27 health
      problems. There was great variation in the responses to this question according
      to the type of health problem presented. Thus for problems such as abdominal pain
      or chest pain, 85% of the GPs reported being the PFC, compared with only 50% for
      problems of suicidal thoughts or alcohol dependence. Multivariate analysis
      revealed that those more likely to report being their patients' PFC for the
      majority of problems presented were specialists in family medicine (p < 0.001),
      physicians under the age of 55 (p < 0.01) and rural physicians (p < 0.05). Our
      findings support the model which proposes that characteristics of the physician,
      the type of problem presented, and characteristics of the environment influence
      the likelihood of the GP being the patient's PFC. The findings have implications
      for GP training programs designed to enable GPs to cope with the wide range of
      problems encountered in general practice and to provide high quality care at
      reasonable cost.

PMID- 8549976
TI  - [Is routine monitoring of theophylline blood levels really effective?].
AB  - Theophylline is widely used by patients with asthma and chronic obstructive
      pulmonary disease as a bronchodilator. The therapeutic range is relatively
      narrow: 10-20 mcg/ml. In a survey of 344 blood samples from 290 patients over a
      period of 12 months, 60% had levels lower than 10 mcg/ml, and only 28% were
      within the therapeutic range. This was especially the case among those using oral
      preparations. Our data raise several questions concerning the individualization
      of theophylline dosage, the effectiveness of its routine blood monitoring, and
      the implications of these results for ambulatory patients who are possibly being
      under treated.

PMID- 8549977
TI  - [Malignant salivary gland tumors].
AB  - Records of 60 patients with primary salivary gland tumors were retrospectively
      analyzed. Most were European Jews, 60% were males, and the average age was 57
      years. The parotid gland was the most frequent site of origin (76%). The main
      presenting symptom was painless swelling. Pain or facial palsy were rare and
      associated with poor prognoses. The most common types were mucoepidermoid,
      adenocystic, adenocarcinoma and malignant, mixed carcinomas (in descending order
      of frequency). Squamous cell carcinoma was the most prevalent histologic type.
      Most patients presented at an advanced stage. Treatment was mainly surgical and
      postoperative radiotherapy was given to those with advanced disease. Most
      recurrences occurred within 3 years of initial treatment. Actuarial 10-year
      survival for all patients was 40%. Superior survival rates were achieved in
      women, probably due to less aggressive malignancies. Low grade mucoepidermoid
      carcinoma had a favorable prognosis, whereas anaplastic carcinoma had the worst.
      Other significant prognostic factors included stage and grade of disease.

PMID- 8549978
TI  - [Percutaneous drainage of splenic abscesses under ultrasound].
AB  - A splenic abscess is considered life-threatening. Traditionally the treatment of
      choice has been splenectomy, which has relatively high morbidity and mortality
      and results in increased susceptibility to infection. Percutaneous drainage can
      be an alternative treatment for splenic abscesses and might avoid splenectomy. 2
      cases of splenic abscess are presented: 1 had typhoid fever and the other had had
      a left hemicolectomy. In both cases external aspiration was performed twice and a
      catheter was left in the drained cavity after the second aspiration. There was no
      clinical improvement in the patient with typhoid fever and splenectomy had to be
      performed. In the other drainage was followed by marked regression of symptoms.
      We suggest that percutaneous drainage can be safely used for splenic abscesses.
      Splenectomy should be reserved for those in whom drainage does not lead to
      improvement.

PMID- 8549979
TI  - [Once upon a time there was a schizophrenic].
AB  - A series of 4 schizophrenic patients is described. In 2 it was unequivocally
      shown that acute outbreaks of "positive" symptoms were expressions of
      intrapsychic conflicts and in 1, the result of a therapist's error. In the first
      case, when the conflict was resolved, symptoms disappeared. 2 other cases were in
      the chronic phase. In both, long-term dynamically oriented psychotherapy resulted
      in reappearance of "lost" cognitive and affective functions. Thus, "negative"
      symptoms (so-called post-psychotic defects) are amenable to psychotherapy and
      potentially reversible. Concern is expressed about the exclusive biological
      approach to the understanding and treatment of schizophrenia.

PMID- 8549980
TI  - [Acute renal failure due to non-traumatic rhabdomyolysis in a cocaine addict].
AB  - Nontraumatic rhabdomyolysis in drug abusers is well-known, with cocaine and
      parenteral heroin the most frequent causative agents. Rhabdomyolysis is thought
      to result from compromised vascular supply to dependent muscles, due to prolonged
      pressure during long periods of depressed consciousness and immobility. However,
      recent work in rats has shown marked vasodilatation in areas of injured muscle,
      mediated by the nitric oxide pathway. Acute renal failure occurs in about 2/3 of
      the cases of cocaine-associated rhabdomyolysis. The usual clinical picture is
      that of a mentally obtunded drug addict presenting with swelling and tenderness
      of the muscles of a limb. However, these findings may be absent or overlooked.
      Characteristic laboratory features include elevated serum creatinine
      phosphokinase (CPK) (in excess of 90,000 IU/L) and myoglobinuria. We present a 33
      year-old male addict who developed acute renal failure due to cocaine- and heroin
      associated rhabdomyolysis. He had marked edema and tenderness of his right leg
      and was initially erroneously diagnosed as suffering from deep venous thrombosis.
      Only when the CPK was found to be 47,300 U/L, was the correct diagnosis made.
      Massive fluid replacement and alkalinization of the urine resulted in rapid
      improvement in renal function.

PMID- 8549981
TI  - [Laparoscopic unroofing of a giant renal cyst].
AB  - Simple cysts of the kidney represent a common abnormality. They may be single or
      multiple and usually are asymptomatic. However, occasionally they may cause pain
      and hematuria. Open surgical unroofing eliminates the cyst but may incur
      postoperative complications and prolonged hospitalization. Laparoscopic unroofing
      of symptomatic renal cysts has recently been described, but only a few cases have
      been reported. We present a 24-year-old man with a giant, painful, renal cyst
      successfully unroofed via transperitoneal laparoscopy.

PMID- 8549982
TI  - [Environmental odor pollution--health significance in humans].

PMID- 8549983
TI  - [Increased mortality after acute myocardial infarction in women: treatment bias
      or a different disease?].

PMID- 8549984
TI  - [The use of computerized image analysis of tissue specimens and cell cultures in
      the early identification and the understanding of the pathogenesis of malignant
      tumors].

PMID- 8549985
TI  - [Measurement of drugs in neonatal hair--a window to fetal exposure].

PMID- 8549986
TI  - [Apoptosis (programmed cell death) in autoimmunity--autoimmunological aspect].

PMID- 8549987
TI  - [Apoptosis: cell do not die at random--biochemical aspect].

PMID- 8549988
TI  - [Apoptosis--programmed cell death--molecular aspect].

PMID- 8549989
TI  - [Molecular biology of epithelial ovarian carcinoma].

PMID- 8549990
TI  - [Prognosis in systemic lupus erythematosus].

PMID- 8549991
TI  - Overproduction of the Hsd subunits leads to the loss of temperature-sensitive
      restriction and modification phenotype.
AB  - The genes hsdM and hsdS for M. EcoKI modification methyltransferase and the
      complete set of hsdR, hsdM and hsdS genes coding for R. EcoKI restriction
      endonuclease, both with and without a temperature-sensitive (ts) mutation in hsdS
      gene, were cloned in pBR322 plasmid and introduced into E. coli C (a strain
      without a natural restriction-modification (R-M) system). The strains producing
      only the methyltransferase, or together with the endonuclease, were thus
      obtained. The hsdSts-1 mutation, mapped previously in the distal variable region
      of the hsdS gene with C1 245-T transition has no effect on the R-M phenotype
      expressed from cloned genes in bacteria grown at 42 degrees C. In clones
      transformed with the whole hsd region an alleviation of R-M functions was
      observed immediately after the transformation, but after subculture the
      transformants expressed the wild-type R-M phenotype irrespective of whether the
      wild-type or the mutant hsdS allele was present in the hybrid plasmid.
      Simultaneous overproduction of HsdS and HsdM subunits impairs the ts effect of
      the hsdSts-1 mutation on restriction and modification.

PMID- 8549992
TI  - Yersinia ssp. in surface water in San Luis, Argentina.
AB  - Yersinia spp. was examined in three rivers and two lakes located in the Province
      of San Luis, Argentina, over a 1-year period. Water samples were concentrated
      either by Moore's gauze technique or by filtering through diatomaceous earth.
      Five enrichment media: yeast extract--Bengal rose broth (YER) with bile-oxalate
      sorbose broth (BOS); 67 mmol/L phosphate-buffered saline (pH 7.6; PBS); PBS
      enriched with a 1% mannitol and 1% peptone (PBSMP); PBS with lyzed 0.5% sheep
      blood (PBSB); Wauters broth (W); and five plating media: Mac Conkey agar (MC);
      Salmonella--Shigella agar (SS); 5% sheep blood agar (BA); lactose-sucrose-urea
      agar (LSU) and irgasan-novobiocin agar (IN) were used. The following strains were
      isolated: Y. intermedia B1 O:4,32-4,33 Lis Xz (four strains), Y. intermedia B1
      O:57 Lis Xo (one strain), Y. intermedia B2 O:57 Lis Xo (one strain), Y.
      enterocolitica B1 O:10-34 Lis Xz (one strain), and Y. frederiksenii undetermined
      biovar, O:16-16,29 Lis Xz (two strains). The incidence of isolation of Yersinia
      spp. was 7.14%. YER-BOS proved to be the best enrichment method since it allowed
      the highest recovering Yersinia spp. strains. Among plating media, the best
      results were obtained with MC. Apparently, the isolation of Yersinia spp. can be
      related to environmental variables such as temperature differences between cold
      and warm seasons. Negative results obtained during virulence assays suggest that
      isolated strains lack the pathogenic potential against man.

PMID- 8549993
TI  - Development of high-molar-mass cellobiase complex by spontaneous protein-protein
      interaction in the culture filtrate of Termitomyces clypeatus.
AB  - The 450 kDa cellobiase from Termitomyces clypeatus which migrates as a single
      band on IEF, PAGE and SDS-PAGE, was found to possess appreciable sucrase
      activity. The fungus produced sucrase and cellobiase constitutively in different
      media but with different activity ratios. The kinetics of secretion of the two
      enzymes was similar under in vivo and in vitro conditions. HPGPLC analysis of the
      culture filtrates indicated the presence of both sucrase and cellobiase in the
      same protein fractions of different molar mass, even in the 30-kDa protein
      fraction. No free sucrase or cellobiase could be detected in the culture
      filtrates. It was also observed that fractionation of cellobiase by (NH4)2SO4
      precipitation was different with different amounts of associated sucrase activity
      present in the culture filtrate. The (NH4)2SO4-precipitated cellobiase fraction
      also contained cellobiases in proteins of widely varied molar mass ranges.
      However, none of the low-molar mass proteins other than the 450-kDa enzyme could
      be purified, as all low-molar-mass fractions spontaneously aggregated to the 450
      kDa enzyme. Hydrophobic chromatography of the (NH4)2SO4-precipitated fractions
      followed by HPGPLC of the eluted active fraction yielded both cellobiase-free
      sucrase and a very low sucrase-containing cellobiase fraction. The cellobiase
      fraction, homogeneous in PAGE, was also a high-molar-mass protein complex
      dissociating into a number of protein bands on SDS-PAGE.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8549994
TI  - Structure-activity relationships of some 4-quinazolylthiosemicarbazides and their
      triazolo derivatives.
AB  - Eight 4-quinazolylthiosemicarbazides and nine of their structural analogues have
      been tested for antibacterial effects and for structure activity relationships. 9
      Chloro-5-morpholino-1,2,4-triazolo[4,3-c]quinazoline-3-thione has demonstrated
      the highest antibacterial effect (MIC of 1 mg/L for E. coli and P. mirabilis and
      < 1 mg/L for S. aureus and B. subtilis). The most effective derivatives have the
      carbon aromatic ring substituted with chlorine and the pyrimidine ring with
      morpholine or with secondary amine group.

PMID- 8549995
TI  - Acid phosphatase synthesis in Aspergillus flavus.
AB  - Proteins with phosphatase activity were produced during the growth of Aspergillus
      flavus in a phosphate-supplemented liquid synthetic medium. The best carbon and
      nitrogen sources for the synthesis of phosphatase were glucose and ammonium
      sulfate, respectively. The proteins were separated by molecular exclusion and ion
      exclusion chromatography (IEC) into three components one of which showed
      phosphatase activity. The molar mass of the enzyme was approximately 62 kDa. The
      purified enzyme exhibited an optimum activity at pH 4.0 and at 45 degrees C. The
      activity of the enzyme was stimulated by Ca2+ and Mg2+ but inhibited by fluoride,
      iodoacetic acid, ethylenediaminetetraacetic acid and 2,4-dinitrophenol, and
      exhibited an apparent KM of approximately 420 mumol/L.

PMID- 8549996
TI  - Phytase from Aspergillus niger.
AB  - 132 microorganisms, isolates from soil and decayed fruits, were tested for
      phytase production. All isolates intensively producing active extracellular
      phytase were of fungal origin. The most active fungal isolates with phytase
      activity were identified as Aspergillus niger. At the end of the growth phase,
      the extracellular phytase activity produced by A. niger strain 92 was 132
      nkat/mL, with strain 89 it was 53 nkat/mL. In both strains the extracellular
      enzyme activity exhibited two marked activity optima at pH 1.8 and 5.0 and a
      temperature optimum at 55 degrees C.

PMID- 8549997
TI  - New search for pectolytic yeasts.
AB  - A new screening method for pectin-depolymerizing microorganisms is described. The
      method is based on precipitation of non-hydrolyzed citrus pectin with
      hexadecyltrimethylammonium bromide in a medium solidified with a bacterial
      gelling gum. A substrate depolymerized by the secreted enzymes does not
      precipitate, and the positive strains thus show transparent areas around the
      colonies. The method was used to screen 300 yeast and yeast-like microorganisms
      belonging to 52 different genera. The secretion of pectin-depolymerizing enzymes
      occurred with different frequencies in 13 genera (69 positive strains of 207
      tested), the lowest frequency being found in the genus Candida (13 positive out
      of 125 strains tested) and the highest frequency in the genera Aureobasidium (4
      of 6) Cryptococcus (29 of 38), Geotrichum (4 of 9), Kluyveromyces (5 of 5),
      Rhodosporidium (2 of 2), Leucosporidium (2 of 2), Trichosporon (3 of 6) and
      Ustilago (2 of 2). Strains giving the highest number of harvested cells after
      growth on pectin in a liquid medium have been identified.

PMID- 8549998
TI  - An expert system applied to the physiological analysis of early stage of beer
      fermentation.
AB  - A fuzzy expert system was applied to the knowledge analysis of yeast physiology
      in the early stage of beer fermentation, when the wort was aerated. We used
      ergosterol and glycogen concentration in the wort as a suitable marker of
      physiological state of the cell population. The amount of both compounds
      influences the rate of fermentation, cell growth and the final taste of beer. The
      concentrations of ergosterol and glycogen including the number of cells can not
      be measured immediately during the relatively short aeration period, and
      incomplete experimental data are therefore found in laboratory logbooks. We
      therefore suggested that the fuzzy relation between the directly measurable
      dissolved oxygen concentration and the rate of ergosterol or glycogen formation
      should be identified and a fuzzy expert system should be used to analyze the
      behavior of the yeast.

PMID- 8550000
TI  - 12th SMYTE (Small Meeting on Yeast Transport and Energetics) held in Karpacz
      (Poland)--September 15-17, 1994 organized by Prof. T. M. Lachowicz.

PMID- 8549999
TI  - Effect of Bacillus firmus and other sporulating aerobic microorganisms on in
      vitro stimulation of human lymphocytes. A comparative study.
AB  - B. firmus activates human peripheral blood lymphocytes in vitro. Bacteria
      inactivated by heat or by formaldehyde were about equally effective, stimulating
      the blastic transformation of lymphocytes at doses of 10-200 mg/L and Ig
      formation in the culture at 10-500 mg/L. The action of formaldehyde treated B.
      firmus was compared with that of analogously inactivated B. subtilis, B.
      polymyxa, B. coagulans, B. megaterium, B. pumilus, B. cereus and B. lentus at a
      concentration of 100 mg/L. All these bacilli mildly stimulated blastic
      transformation and most of them substantially stimulated Ig formation, but B.
      firmus was the most efficient in stimulating the formation of Ig of all classes,
      in particular IgM and IgA. Its effect on Ig formation was comparable with that of
      PWM and was unusually high as compared with that of other bacteria. B. firmus is
      apparently a strong polyclonal activator of B lymphocytes. Its cells or their
      components could be potentially used for modulating immune reactions.

PMID- 8550001
TI  - Inward and outward rectifying potassium currents in Saccharomyces cerevisiae
      mediated by endogenous and heterelogously expressed ion channels.
AB  - Disruption of genes encoding endogenous transport proteins in Saccharomyces
      cerevisiae has facilitated the recent cloning, by functional expression, of cDNAs
      encoding K+ channels and amino acid transporters from the plant Arabidopsis
      thaliana [1-4]. In the present study, we demonstrate in whole-cell patch clamp
      experiments that the inability of trk1deltatrk2delta mutants of S. cerevisiae to
      grow on submillimolar K+ correlates with the lack of K+ inward currents, which
      are present in wild-type cells, and that transformation of the trk1deltatrk2delta
      double-deletion mutant with KAT1 from Arabidopsis thaliana restores this
      phenotype by encoding a plasma membrane protein that allows large K+ inward
      currents. Similar K+ inward currents are induced by transformation of a trk1
      mutant with AKT1 from A. thaliana.

PMID- 8550002
TI  - Metabolic studies on synchronized yeast cells in continuous culture.

PMID- 8550003
TI  - Transport of lactate and its regulation in Saccharomyces cerevisiae mutants
      deficient in specific metabolic steps.

PMID- 8550004
TI  - Utilization of acetic acid and other short-chain monocarboxylic acids in the
      yeasts Torulaspora delbrueckii and Saccharomyces cerevisiae: transport and its
      regulation.

PMID- 8550005
TI  - Genetic and molecular characterisation of purine permease genes of Aspergillus
      nidulans reveals a novel family of transporters conserved in prokaryotes and
      eukaryotes.
AB  - The ascomycete fungus Aspergillus nidulans can utilize purines (adenine, guanine,
      hypoxanthine, xanthine, and uric acid) as sole nitrogen sources [1]. The
      expression of most structural genes involved in the pathway of purine uptake and
      catabolism is subject to uric acid induction, mediated by the product of the
      positive regulatory gene uaY, and to nitrogen metabolite repression, mediated by
      the product of the general, positive-acting, GATA-like transcription factor,
      encoded by the areA gene [1].

PMID- 8550006
TI  - Hexokinases and catabolite repression in Candida utilis.

PMID- 8550007
TI  - Study of membrane potential changes of yeast cells caused by killer toxin K1.

PMID- 8550008
TI  - Effect of H2O2-induced oxidative stress on some yeast membrane functions.

PMID- 8550009
TI  - Sodium tolerance depends on the capacity to transport potassium in Saccharomyces
      cerevisiae.

PMID- 8550010
TI  - Problems in the use of benzoic acid for estimating the internal pH of yeasts.

PMID- 8550011
TI  - Monitoring of membrane potential by means of fluorescent dyes and time-resolved
      fluorescence spectroscopy.

PMID- 8550012
TI  - Effects of the NTH1 gene disruption in bakers' yeast.

PMID- 8550013
TI  - Are the pH-sensitive mutants members of the VMA family?

PMID- 8550014
TI  - The low-affinity component of the glucose transport system in Saccharomyces
      cerevisiae is not due to passive diffusion.

PMID- 8550015
TI  - The FPS1 gene product functions as a glycerol facilitator in the yeast
      Saccharomyces cerevisiae.

PMID- 8550016
TI  - The roles of multiple hexose transporters in S. cerevisiae.

PMID- 8550017
TI  - Involvement of endocytosis in catabolite inactivation of the transport systems in
      Saccharomyces cerevisiae.

PMID- 8550018
TI  - Effects of potassium on the expression and stability of the general amino acid
      permease of Saccharomyces.

PMID- 8550019
TI  - Candida albicans gene CAN1 is highly homologous to other yeast and E. coli genes
      coding for amino acid permeases.

PMID- 8550020
TI  - Structure-function analysis of the proline permease (PRNB) of the filamentous
      fungus Aspergillus nidulans.

PMID- 8550021
TI  - The Kluyver effect in Saccharomyces cerevisiae for trehalose and the isolation of
      putative trehalose uptake mutants from Saccharomyces exiguus.

PMID- 8550022
TI  - Endocytose and degradation of the uracil permease of S. cerevisiae under stress
      conditions: possible role of ubiquitin.

PMID- 8550023
TI  - Rapid kinetics of glucose uptake in Saccharomyces cerevisiae.
AB  - In a multiple deletion mutant hxt1deltahxt2deltahxt3delta hxt4deltasnf3delta of
      Saccharomyces cerevisiae growing on a 2% glucose, high-affinity glucose-uptake
      (low Km) was exhibited throughout growth on glucose in contrast to the wild-type,
      which exhibited the usual low-affinity to high-affinity transition as the glucose
      in the medium was consumed. Elevated levels of invertase activity throughout
      growth on glucose, in this mutant as compared to the wild-type, indicate that
      glucose repression may be impaired. However, in a mutant containing only the HXT2
      gene (hxt1deltahxt3deltahxt4deltasnf3delta), invertase levels were similar to
      those in the wild-type. It is likely, therefore, that some of these putative
      glucose transporters, such as HXT2, also have regulatory roles in cellular
      metabolism. In triple hexose-kinase mutants, rapid (200-ms) measurements of
      initial glucose-uptake revealed high-affinity glucose uptake (Km approx. 2
      mmol/L) while measurements on the slower 5-s scale clearly demonstrate that
      uptake is not linear over this longer period. These results suggest that this
      high-affinity component does not require a functional hexose-kinase.

PMID- 8550024
TI  - General biological properties of antioxidant permeatoxins and their influence on
      natural and model membranes.

PMID- 8550025
TI  - Effect of isoniazid on glutathione biosynthesis and degradation in Mycobacterium
      smegmatis.
AB  - The mechanism of glutathione (GSH) depletion by isoniazid (INH) was studied in M.
      smegmatis. INH increased the activity of gamma-glutamyl transferase (GGT) whether
      added before medium inoculation or to actively growing cells. The activity of GGT
      in cells grown from the beginning in INH-containing medium increased
      significantly on growth days 2-6. Three-day old M. smegmatis cells treated with
      INH exhibited a 30-65% increase in the activity of GGT. The activities of gamma
      glutamyl-cysteine synthase (GGCS) and GSH synthase (GS) were lowered by 50 and
      56% respectively on the second day of growth when M. smegmatis was grown in a
      medium supplemented with 1.5 mg INH per L. In 3-day old M. smegmatis, INH
      significantly inhibited the activities of GSH biosynthetic enzymes. The results
      demonstrate that the increased activity of GGT and decreased activities of GSH
      biosynthetic enzymes are responsible for GSH depletion by INH in M. smegmatis.

PMID- 8550026
TI  - Occurrence of Fusarium sacchari var. subglutinans and its mycotoxin production
      ability in broiler feed.
AB  - Spores of Fusarium sacchari var. subglutinans isolated from broiler feed BR1 were
      obtained at an average concentration of 1.5/mg in 25% of tested samples. The
      spore concentration was increased from 1 to 100/mg of solid substrate (BR2;
      biscuit) or to 1/nL of Sabouraud broth after 3 weeks of cultivation. Mycotoxin
      analyses of these three substrates showed negative reactions for T-2 toxin and
      zearalenone but a positive reaction for deoxynivalenol (DON) which was found in
      concentrations of 5 ppm in Sabouraud broth, 50 ppm in BR2 and 220 ppm in biscuit.
      Therefore, our F. sacchari isolate appeared to be a DON producer.

PMID- 8550027
TI  - Serological difference between Erwinia herbicola strains of plant and human
      origin.
AB  - Fifty Erwinia herbicola isolates obtained from host plants were examined in an
      agglutination reaction with antiserum prepared against E. ananas (E. herbicola)
      strain CCM 2407 antigen of plant origin and with antiserum prepared against
      Enterobacter agglomerans strain CNCTC M 269 antigen of human origin. In tests
      with strain CCM 2407 antiserum, 56% isolates showed a positive reaction, while in
      tests with strain CNCTC M 269 antiserum only 14% isolates showed a positive
      reaction. Among E. herbicola isolates which showed a positive reaction with CCM
      2407 antiserum 18% showed a positive reaction with the CNCTC M 269 antiserum too.
      Our results confirmed the serological heterogeneity of E. herbicola population.
      In spite of the difference in the origin of the two antigens used for the
      preparation of antisera (plant, human; Japan, Czech Republic) our results
      indicate that some of our E. herbicola strains and E. agglomerans strain CNCTC M
      269 are serologically identical.

PMID- 8550028
TI  - Ganciclovir treatment of hepatitis B virus infection in liver transplant
      recipients.
AB  - To determine the safety and efficacy of ganciclovir treatment of hepatitis B
      virus (HBV) infection after liver transplantation, nine patients (seven males,
      two females; mean age, 38 years) with posttransplant HBV infection were treated
      with ganciclovir for 3 to 10 months. Ganciclovir was administered intravenously
      at an initial dose of 5 mg/kg/d and then increased to 10 mg/kg/d.
      Immunosuppressive drug therapy was maintained at low levels. There were no major
      side effects of ganciclovir therapy. Serum HBV DNA levels decreased by a mean of
      90% (range, 42% to 100%), and four of nine patients had no measurable HBV DNA at
      the completion of therapy. Mean serum alanine aminotransferase levels decreased
      by 83%. Hepatic expression of HBV antigens and HBV DNA was assessed before and
      after therapy in six patients and found to be reduced in three patients. The
      histology activity index was also stabilized or improved in all patients. After
      discontinuation of therapy, four of nine patients underwent retreatment for 4- to
      12-fold elevation of serum HBV DNA and/or biochemical and clinical relapse, that
      was severe in one patient. This pilot study shows the safety and efficacy of
      ganciclovir therapy for reducing HBV replication in patients with HBV infection
      after liver transplantation.

PMID- 8550029
TI  - Hepatocyte proliferation induced in rats by lead nitrate is suppressed by several
      tumor necrosis factor alpha inhibitors.
AB  - Lead nitrate induces liver cell proliferation in rats without accompanying liver
      cell necrosis. However, the mechanism of this proliferation and its effect on
      hepatocytes remain unknown. Therefore, we examined the liver and blood level of
      hepatocyte growth factor and tumor necrosis factor alpha (TNF-alpha) at various
      intervals to determine whether lead nitrate modifies hepatocyte proliferation by
      altering the production of these cytokines. We also administered several TNF
      alpha inhibitors, dexamethasone, adenosine, (2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4
      benzoquinoyl)]-2-nonyl-2- propenoic acid (E 3330), and pentoxifylline, to rats to
      clarify whether pretreatment with these inhibitors suppresses the increase of TNF
      alpha messenger RNA (mRNA) in the liver and prevents the hepatocyte proliferation
      induced by lead nitrate. Hepatocyte proliferation occurred by 24 hours and
      reached a peak 48 hours after a single intravenous injection of lead nitrate (100
      mumol/kg). TNF-alpha mRNA expression in the liver was increased 1, 6, and 12
      hours after the injection, whereas no alteration was observed in liver or blood
      level of hepatocyte growth factor. Pretreatment with dexamethasone (4.0 mg/kg),
      E3330 (100 mg/kg) adenosine (0.3 mmol/kg), and pentoxifylline (100 mg/kg),
      inhibited both TNF-alpha mRNA expression and hepatocyte proliferation 48 hours
      after the injection. These experimental results strongly support the hypothesis
      that TNF-alpha positively regulates the hepatocyte proliferation induced in rats
      by the mitogen, lead nitrate.

PMID- 8550030
TI  - Identification of the 37-kd rat liver protein that forms an acetaldehyde adduct
      in vivo as delta 4-3-ketosteroid 5 beta-reductase.
AB  - Acetaldehyde, the first product of alcohol metabolism, is highly reactive.
      Several proteins have been shown to be covalently modified by acetaldehyde in
      vivo. We have previously reported the detection of a cytosolic 37-kd protein
      acetaldehyde adduct (-AA) in the liver of alcohol-fed rats. The liver extract
      from an alcohol-fed rat was subjected to 2-dimensional (2D) sodium dodecylsulfate
      (SDS)-polyacrylamide gel electrophoresis (PAGE), transferred to polyvinylidene
      difluoride (PVDF) membrane, and the 37-kd protein-AA spot was digested with
      trypsin and sequenced for amino acids. Degenerate oligonucleotides corresponding
      to a peptide sequence of the protein-AA were used as the probe to screen a lambda
      gt11 rat liver complementary DNA (cDNA) library. A clone that extended to a
      potential ATG start codon was identified. The open reading frame was 978
      nucleotides long, encoding 326 amino acid residues. The sequence matched that of
      rat liver delta 4-3-ketosteroid 5 beta-reductase. The cloned cDNA was expressed
      in Escherichia coli using pGEX-KG as the vector. The expressed protein was found
      to be of correct molecular weight. It reacted with an antibody that recognized
      the unmodified liver 37-kd protein by Western blotting. Peptide profiles of
      tryptic-digested recombinant protein and the purified rat liver 37-kd protein
      were similar and yielded the same peptide sequence. delta 4-3-ketosteroid 5 beta
      reductase catalyzes the reduction of key intermediates during bile acid
      biosynthesis. Whether modification of the 5 beta-reductase by acetaldehyde
      affects the enzyme activity and bile acid synthesis remains to be studied.

PMID- 8550031
TI  - Prostaglandins modulate the responsiveness of the gastric microcirculation of
      sodium nitroprusside in cirrhotic rats.
AB  - Cirrhotic rats have an increased susceptibility to ethanol-induced gastric
      injury, related to an inability to mount a defensive gastric hyperemic response
      to luminal irritants, and associated with an impaired reactivity of the gastric
      microcirculation to nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)
      dependent vasodilators. Whether this hyporesponsiveness is in some way related to
      depressed prostaglandin synthesis by the stomach of cirrhotic rats is not clear.
      The aims of this study were to evaluate the role of NO and prostaglandins in the
      regulation of the gastric microcirculation under resting conditions and in
      response to administration of sodium nitroprusside, as well as to investigate the
      mechanisms of the hyporesponsiveness of the gastric microcirculation to
      nitrovasodilators. Cirrhosis was induced in rats by bile duct ligation, and
      controls had sham-operation. NG-nitro-L-arginine-methyl-ester (L-NAME) and
      indomethacin administration produced a greater reduction in gastric blood flow in
      cirrhotic rats than controls. Indomethacin pretreatment almost completely
      abolished the responsiveness to sodium nitroprusside (NaNP) in cirrhotic rats,
      while not affecting controls. Long-term administration of misoprostol to
      cirrhotic rats restored to normal the responsiveness to NaNP, whereas long-term
      administration of aspirin to healthy rats resulted in a hyporesponsiveness of the
      gastric microcirculation to NaNP similar to that seen in cirrhotic rats. We
      conclude that there are interactions between NO and prostaglandins in regulating
      gastric blood flow in both healthy and cirrhotic rats. The hyporesponsiveness of
      the gastric microcirculation of cirrhotic rats to a nitrovasodilator may occur as
      a consequence of prolonged depression of gastric prostaglandin synthesis.

PMID- 8550032
TI  - Mesenteric vasodilator responses in cirrhotic rats: a role for nitric oxide?
AB  - The contribution of nitric oxide to mesenteric arterial vasodilator responses was
      investigated in the isolated perfused mesenteric arterial bed of cirrhotic rats
      (carbon tetrachloride/phenobarbitone; n = 6). Age-matched (n = 9) and
      phenobarbitone-treated rats (n = 9) served as controls. Responses to the
      endothelium-dependent dilators acetylcholine and adenosine 5'-triphosphate (ATP)
      and the smooth muscle dilator (NO donor) sodium nitroprusside were investigated
      after tone was raised by continuous infusion of methoxamine, before and during
      infusion of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME;
      30 mumol/L) +/- L-arginine (1 mmol/L). A significant hyporesponsiveness to
      methoxamine infusion in cirrhotic preparations (P < .05) was not fully corrected
      by L-NAME. There was no difference in the percentage vasodilator response to
      acetylcholine in the cirrhotic group compared with controls; L-NAME significantly
      and reversibly inhibited the dilator response in all groups. ATP elicited dose
      dependent vasodilation that, in the absence of L-NAME, did not differ between the
      groups. By contrast, in the presence of L-NAME, ATP (5 x 10(-8) mol) produced
      pronounced, reversible vasoconstriction only in cirrhotic animals (P < .02).
      Vasodilatation attributable to sodium nitroprusside (5 x 10(-8) mol) was
      significantly attenuated in cirrhotic rats. The methoxamine data support the
      concept of mesenteric hyposensitivity to vasoconstrictor agents in cirrhosis that
      may be at least partly NO mediated. Increased NO activity in smooth muscle
      leading to decreased guanylate cyclase availability may account for the
      diminished vasodilator responses to sodium nitroprusside in cirrhotic
      preparations. The unchanged responsiveness to vasodilatation by acetylcholine
      (ACh) and the vasoconstriction to ATP observed during NO blockade in cirrhotic
      animals indicate that mesenteric endothelial NO is unchanged or possibly
      diminished.

PMID- 8550033
TI  - Direct measurement of hepatic indocyanine green clearance with near-infrared
      spectroscopy: separate evaluation of uptake and removal.
AB  - We continuously measured hepatic absorbance of indocyanine green (ICG) using near
      infrared (NIR) spectroscopy after intravenous bolus injection in rabbits. Hepatic
      ICG concentration was obtained by subtracting out the absorbance of hemoglobin
      and other pigments within the liver. Two exponential rate constants, the first
      reflecting the dye uptake from plasma to the hepatocytes, and the second
      representing the dye removal from the liver by cytoplasmic transport and biliary
      excretion, were determined by fitting the time-course curve of hepatic ICG
      concentration to a two-compartment model with irreversible transfer between the
      two compartments, as defined by the double-exponential equation: [ICG]liver(t) = 
      A exp(-alpha t) + B exp(-beta t). The results showed that treatment with
      bilirubin, a competitive inhibitor of ICG uptake, caused a decrease in alpha.
      Treatment with either colchicine, which is toxic to microtubules, or with
      ouabain, an inhibitor of Na+,K(+)-ATPase, caused a decrease in beta. These
      results were compatible with the kinetic model. This new method was then used in
      liver-injured rabbits inflicted with hemorrhagic shock and ischemia-reperfusion,
      to show that the first rate constant is primarily affected by hepatic
      microcirculatory condition, and the second refers closely to parenchymal liver
      damage. In another series of partial liver ischemia-reperfusions, it was possible
      to simultaneously and separately monitor the ICG profiles of post-ischemic and
      nonischemic areas. Thus, the kinetic analysis of hepatic ICG concentration
      curves, as directly measured by NIR spectroscopy, led to the separate evaluation
      of different clearance process of ICG in the liver, suggesting the advanced
      utility as a comprehensive liver function test.

PMID- 8550034
TI  - Appearance of oval cells in the liver of rats after long-term exposure to
      ethanol.
AB  - Epidemiological studies show an increased risk of developing liver cancer among
      alcoholics. There is some agreement that ethanol itself is not carcinogenic, but
      it may enhance the tumorigenic process by inducing drug-metabolizing enzymes,
      suppression of the immune system or by affecting DNA repair enzymes. Precisely
      how ethanol predisposes or promotes the development of hepatoma is unknown.
      Hepatocarcinogenesis induced by a choline-deficient, ethionine-supplemented (CDE)
      diet produces extensive alteration of the liver architecture with the emergence
      and rapid proliferation of oval cells. This study examines whether chronic
      alcohol consumption induces the proliferation of oval cells. Oval cells induced
      in rats maintained on a 5% ethanol liquid diet (ELD) for up to 24 months, or fed
      a CDE diet for up to 4 weeks, are compared using a panel of liver-specific
      markers. In CDE-treated rats, oval cells staining positively for alpha
      fetoprotein (AFP), pi-class glutathione S-transferase (pi GST), and the embryonic
      form of pyruvate kinase (M2-PK) are observed after 1 week. Similar cells are seen
      in ELD-treated rats after 2 months. Their numbers increase with time, and
      incorporation of [3H]thymidine confirms they are a dividing population. Acute
      damage induced by partial hepatectomy and CCI4 poisoning did not induce the
      appearance of oval cells. We conclude that chronic ethanol consumption induces
      oval cell proliferation. We suggest that, in addition to other proposed
      mechanisms, an alteration in cellular composition of the liver be considered as
      an explanation for the increased incidence of liver cancer among alcoholics.

PMID- 8550035
TI  - Role of cytochrome P4502E1-dependent formation of hydroxyethyl free radical in
      the development of liver damage in rats intragastrically fed with ethanol.
AB  - We have previously shown that the treatment with diallyl sulfide (DAS) and
      phenylethyl isothiocyanate (PIC) of rats receiving ethanol in the alcohol tube
      feeding model effectively suppressed the induction of cytochrome P4502E1 (CYP2E1)
      by ethanol. Here we report that rat treatment with DAS and PIC significantly
      decreased the trapping of hydroxyethyl free radicals in liver microsomes
      incubated in vitro with ethanol. Furthermore, these inhibitors also greatly
      reduced the production of hydroxyethyl radical-derived epitopes detectable in
      vivo in the liver of ethanol-fed rats. The action of DAS and PIC on the formation
      of hydroxyethyl radicals paralleled their inhibitory effect on lipid peroxidation
      as monitored using, respectively, liver malonildialdehyde (MDA) and plasma lipid
      hydroperoxide levels as well as by the titers of antibodies versus MDA adducts to
      proteins. Thus, these results indicated a link between the induction of CYP2E1 by
      ethanol, the formation of hydroxyethyl radicals and the stimulation of lipid
      peroxidation. The pathological scores in the livers of rats fed with ethanol plus
      or minus DAS and PIC also correlated with levels of hydroxyethyl radical-derived
      epitopes. Rats fed intragastrically with ethanol developed antibodies and the
      formation of these antibodies was greatly reduced by DAS and PIC. Taken together
      these results suggest that CYP2E1 plays an important role in the generation of
      hydroxyethyl radicals during chronic alcohol feeding and that ethanol-derived
      free radicals might play a role in the onset of liver injury in this model of
      alcohol administration.

PMID- 8550036
TI  - Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome
      in cirrhosis. International Ascites Club.

PMID- 8550038
TI  - Hemolysis after transjugular intrahepatic portosystemic shunting: the naked stent
      syndrome.

PMID- 8550037
TI  - Cytokine inhibition of the hepatitis B virus core promoter.
AB  - Hepatitis B virus (HBV) DNA contains consensus elements for transactivating
      proteins whose binding activity in other systems is regulated by inflammatory
      cytokines. Because HBV replicates within an environment of provoked inflammation,
      we speculated that the HBV core/pregenomic promoter may be regulated by cytokines
      produced in response to infection. To evaluate this hypothesis, the HBV
      core/pregenomic (C/P) promoter and associated cis-acting elements were placed
      upstream of a luciferase-encoding plasmid. This reporter construct was
      transfected into cytokine-sensitive hepatoma cells permissive for HBV
      replication, which were exposed to stimulated mononuclear cell-conditioned medium
      or human recombinant cytokines. Conditioned medium reduced luciferase expression
      by 80%. Tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma),
      and interferon alfa (IFN-alpha) each reduced luciferase activity by 40%.
      Combinations of TNF-alpha and interferons mimicked the extent of conditioned
      medium inhibition. Non-specific effects from diminished cellular viability or
      growth were not responsible for decreased luciferase activity. Retention of HBV
      DNA 330 basepairs upstream of the C/P transcription start site was required to
      maintain the TNF-alpha effect. A 60% reduction in HBV replicative forms within
      intracellular core particles was demonstrated with TNF-alpha treatment of Hep G2
      cells stably transfected with HBV DNA. The inhibitory action of these cytokines
      implicates a noncytolytic mechanism by which antigen-nonspecific immune responses
      in part regulate HBV replication in infected hepatocytes. This function may be
      beneficial in accelerating viral clearance, but in alternative circumstances
      could contribute to viral persistence by attenuating immunogen recognition.

PMID- 8550039
TI  - Yes, there is (quality of) life after liver transplantation!

PMID- 8550040
TI  - Precore mutants revisited.

PMID- 8550041
TI  - Further comments on the importance of serum potassium concentrations on early
      hepatic encephalopathy.

PMID- 8550042
TI  - Biliary sludge: necessity for a better distinction between crushable and
      noncrushable microconcrements. Sludge is responsible for symptoms not by itself,
      but also in relationship to the variability of the container, i.e., the bile
      tract wall.

PMID- 8550043
TI  - Hepatic stellate cell nomenclature.

PMID- 8550044
TI  - The hepatic microcirculation in the isolated perfused human liver.
AB  - In cirrhosis, capillarization of sinusoids could result in impaired exchanges
      between the hepatocytes and the blood perfusing the liver and contribute to liver
      failure irrespective of the metabolic capacity of the liver. To characterize
      anomalies of the hepatic microcirculation, we used the multiple-indicator
      dilution approach in isolated perfused livers obtained from patients with
      cirrhosis at the time of transplantation, and from organ donors with normal or
      near-normal livers or hepatic steatosis. In organ donors, the sinusoidal volume
      and the permeability of sinusoids to albumin, sucrose, and water were found to be
      comparable to that of normal dog and rat livers. The sinusoidal volume and the
      extravascular volume (EVV) accessible to diffusible tracers were larger after
      hepatic artery than after portal vein injection, probably because of an unshared
      arterial sinusoidal bed. In cirrhotic livers, two kinds of alterations were
      found: the appearance of a barrier between the sinusoids and the hepatocytes
      (capillarization) and intrahepatic shunts. The extravascular space accessible to
      albumin decreased with increasing severity of cirrhosis, and the diffusion of
      sucrose in the space of Disse showed a barrier-limited pattern, instead of the
      normal flow-limited behavior. In cirrhotic livers, a correlation was found
      between the hepatic extraction of indocyanine green (ICG) and the extravascular
      space accessible to albumin (r = .84, P < .05), suggesting that the impaired
      access of this protein-bound dye to the hepatocyte surface contributed to its
      impaired elimination. Intrahepatic shunts were found between portal and hepatic
      vein (21% +/- 16% of portal flow), but not between hepatic artery and hepatic
      veins. We conclude that (1) the behavior of diffusible tracers in human livers
      with normal liver architecture is comparable to that reported in normal animals;
      (2) the permeability of sinusoids in cirrhotic livers is abnormal, (3)
      permeability changes are related to changes in liver function in cirrhosis.

PMID- 8550045
TI  - The hematologic consequences of transjugular intrahepatic portosystemic shunts.
AB  - Transjugular intrahepatic portosystemic shunts (TIPS) are a recent innovation in
      the management of portal hypertension. In 1992, we had previously described an
      instance of severe hemolysis associated with this procedure. This study was
      undertaken to define and quantify the true incidence of TIPS-associated hemolysis
      and its clinical spectrum, as well as to test the hypothesis that portal
      decompression by TIPS would ameliorate hypersplenism in patients with portal
      hypertension. A total of 60 patients undergoing TIPS for prevention of recurrent
      variceal hemorrhage (n = 40) or refractory ascites (n = 20) were studied. Forty
      patients with cirrhosis who were followed concurrently served as controls. At
      entry, both groups were comparable with the exception of increased ascites in the
      TIPS group. A total of 7 instances of intravascular hemolysis were identified in
      60 TIPS patients, whereas none occurred in controls. Of these, 4 patients were
      asymptomatic and detected on routine laboratory testing. Hemolysis led to a
      greater than 4-g/dL decrease in hemoglobin in 2 patients, 2- to 3-g/dL decrease
      in 2 others and a 3- to 4-gm/dL decrease in 1 patient. Two patients were able to
      compensate for hemolysis and did not develop anemia. In all but 1 case, the
      findings of hemolysis subsided by 12 to 15 weeks; in 1 patient, orthotopic liver
      transplantation was associated with resolution of the hemolysis. Overall, no
      significant changes in white blood cell or platelet counts were observed in
      patients undergoing TIPS despite adequate portal decompression. We conclude that
      TIPS-induced hemolysis occurs in approximately 10% of subjects. However, it is
      self-limited and rarely requires intervention. Potential mechanisms of such
      hemolysis are discussed. TIPS is also not recommended as a means of improving
      platelet counts in patients with severe hypersplenism.

PMID- 8550046
TI  - Allograft rejection in pediatric recipients of living related liver transplants.
AB  - The purpose of this study was to compare the incidence and severity of rejection
      episodes in a group of children receiving living related orthotopic liver
      transplants (LRLT) versus children receiving cadaveric liver transplants (CLT).
      Thirty-eight patients received primary LRLT and 54 patients received CLT during a
      3-year period ending June 1993. Baseline immunosuppression consisted of
      cyclosporin, azathioprine, and corticosteroids. Rejection episodes were confirmed
      by liver histology and were treated initially with pulse intravenous
      methylprednisolone, 10 mg/kg/d for 3 days. Steroid-resistant rejection was
      treated with OKT3 or FK506. The median patient ages were 1.3 years for the CLT
      and .8 years for the LRLT recipients. Acute cellular rejection developed in 78%
      of the CLT grafts and 74% of the LRLT grafts (P = ns). However, steroid-resistant
      rejection was significantly less frequent in the LRLT recipients, 13% versus 43%
      in the CLT recipients (P < .01). Ductopenic rejection was diagnosed in 20% of CLT
      and 8% of LRLT grafts (P < .10), and graft loss caused by rejection was 9% in the
      CLT and 3% in the LRLT group (P = ns). In conclusion, the overall incidence of
      rejection is the same in LRLT and CLT recipients, but LRLT recipients are less
      likely than CLT recipients to develop steroid-resistant rejection or ductopenic
      rejection.

PMID- 8550047
TI  - Quantification of apolipoprotein A-I and B messenger RNA in heavy drinkers
      according to liver disease.
AB  - It has previously been shown that, in heavy drinkers, serum apolipoprotein A-I
      (ApoA-I) levels are closely related to the degree of liver injury: they are at a
      maximum in patients with steatosis, begin to decrease in patients with fibrosis,
      and reach a minimum in patients with severe cirrhosis. In contrast with serum
      ApoA-I variations, serum apolipoprotein B (ApoB) levels are stable. The
      assessment of messenger RNA (mRNA) levels of ApoA-I and ApoB using a quantitative
      competitive polymerase chain reaction (PCR) method was performed in 18 alcoholic
      patients: 8 with normal livers or steatosis (group I), 6 with fibrosis or
      nonsevere cirrhosis (group II), and 4 with severe cirrhosis (group III). For ApoA
      I, group I had higher serum levels (208.4 +/- 37.6 mg/dL mean +/- SE) and mRNA
      levels (0.51 +/- 0.12) than group II (serum 116 +/- 19 mg/dL, P < .01, mRNA 0.40
      +/- 0.11, P < .09) or group III (serum 56.5 +/- 28.6 mg/dL, P < .01, mRNA 0.27 +/
      .02, P = .008). For ApoB, the three groups had similar serum ApoB levels: 129.9
      +/- 37.7, 121 +/- 51, 120.7 +/- 57.4 mg/dL. Group I presented higher levels of
      ApoB mRNA than those of group III (0.68 +/- 0.21 vs. 0.41 +/- 0.18, P < .06).
      There was a significant correlation between serum and mRNA levels of ApoA-I (r =
      .65, P = .003) but no correlation between serum and mRNA levels of ApoB (r = .19,
      NS). We suggest that (1) steatosis is associated with increased ApoA-I mRNA; (2)
      fibrosis is associated with decreased serum ApoA-I, probably caused by a
      posttranscriptional mechanism; (3) severe alcohol-induced cirrhosis is associated
      with a nonspecific decrease in ApoA-I and ApoB mRNA; and (4) in contrast to ApoA
      I mRNA, the ApoB mRNA level makes a slight contribution to the ApoB serum
      concentration.

PMID- 8550048
TI  - Time course of histological progression in primary biliary cirrhosis.
AB  - Histological staging is used for stratification and assessment of treatment
      efficacy in therapeutic trials for primary biliary cirrhosis (PBC). Knowledge of
      the rate of progression of the histological changes would be helpful in the
      design (duration) and conduct of clinical trials. The histological stages were
      recorded for liver biopsies performed annually on 222 patients during a
      randomized, placebo-controlled clinical trial in which therapy with D
      penicillamine (DPCA) was shown to be ineffective. These data were analyzed using
      a Markov model to describe the time course of histological progression in PBC. At
      study entry, 15 patients were stage I, 56 were stage II, 96 were stage III, and
      55 were stage IV. Histological progression was observed after 1 year in 41%, 43%,
      and 35% of the patients, and after 2 years in 62%, 62%, and 50% of the patients
      who were stage I, stage II, and stage III at entry, respectively. After 4 years
      biopsies showed cirrhosis in 31% and 50% of the patients in stage I and stage II
      at entry, respectively. A minority (20%) of the precirrhotic patients showed
      histological stability; sustained histological regression was rarely observed
      (2%). Our data suggest that a majority of patients with PBC will progress
      histologically within 2 years. The distribution of histological stages over time
      may be helpful in determining the number of patients and length of time necessary
      to appreciate a treatment effect on histological progression in clinical trials
      for PBC.

PMID- 8550049
TI  - Autoantibodies from patients with primary biliary cirrhosis recognize a region
      within the nucleoplasmic domain of inner nuclear membrane protein LBR.
AB  - Autoantibodies from rare patients with primary biliary cirrhosis (PBC) recognize
      LBR, or lamin B receptor, an integral membrane protein of the inner nuclear
      membrane. Human LBR has a nucleoplasmic, amino-terminal domain of 208 amino acids
      followed by a carboxyl-terminal domain with eight putative transmembrane
      segments. Autoantibodies against LBR from four patients with PBC recognized the
      nucleoplasmic, amino-terminal domain but not the carboxyl-terminal domain.
      Immunoblotting of smaller fusion proteins demonstrated that these autoantibodies
      recognized a conformational epitope(s) contained within the stretch of amino
      acids from 1 to 60. These results, combined with those of previous studies, show
      that autoepitopes of nuclear membrane proteins are located within their
      nucleocytoplasmic domains and that autoantibodies from patients with PBC
      predominantly react with one domain of a protein antigen. This work also provides
      further characterization of anti-LBR antibodies that have found utility as
      reagents in cell biology research.

PMID- 8550050
TI  - Proliferation, apoptosis, and induction of hepatic transcription factors are
      characteristics of the early response of biliary epithelial (oval) cells to
      chemical carcinogens.
AB  - In this study, we used [3H]thymidine labeling of newly synthesized DNA to examine
      the earliest effects of 2-acetylaminofluorene (2-AAF) on the mitotic activation
      of cells in the adult rat liver, and in situ hybridization analysis to study the
      expression of three transcription factors (HNF1 beta, HNF3 gamma, and HNF4), and
      two of the genes (alpha-fetoprotein [AFP] and albumin) regulated by these
      factors. A low dose of 2-AAF (and its analogs, 2-AF [2-aminofluorene] and N-OH-2
      AAF) elicited a mitogenic response in ductal cells and nondescript periductular
      cells within 24 hours after administration. The compounds also induced the
      expression of HNF1 beta, HNF3 gamma, AFP, and albumin in ductal structures but
      had no detectable effect of HNF4 expression. In contrast, initiation of bile duct
      proliferation by ligation of the common bile duct had no effect on the expression
      of these genes in ductal cells. In addition to inducing a mitogenic response, 2
      AAF resulted in increased numbers of apoptotic cells in the portal areas, a
      process that contributed to overall retention of liver morphology. Our results
      demonstrate that 2-AAF and some of its analogs can elicit a specific mitogenic
      response and induce expression of the "establishment" transcription factors, HNF1
      beta and HNF3 gamma, in ductal cells. Our data provide further support of a
      precursor-product relationship between "stem-like" cells located in ductal
      structures, oval cells, and hepatocytes.

PMID- 8550051
TI  - In vivo infusion of growth factors enhances the mitogenic response of rat hepatic
      ductal (oval) cells after administration of 2-acetylaminofluorene.
AB  - Expression of several growth factors is elevated in rat liver, after induction of
      oval cell proliferation by chemical carcinogens. However, the exact roles played
      by individual factors are not defined. We infused and examined the effects of
      epidermal growth factor (EGF) and hepatocyte growth factor (HGF) on the
      proliferation of ductal and periductal cells after their activation with 2
      acetylaminofluorene (2-AAF). Furthermore, we included studies on urokinase-type
      plasminogen activator (uPA), because Northern blot analysis showed a strong
      coincidence of uPA expression with oval cell proliferation. Low doses of 2-AAF
      were used to activate ductal and periductal cells, whereafter growth factors were
      infused. Infusion of EGF, HGF, uPA, or any combination thereof for up to 7 days
      resulted in increased numbers of [3H]thymidine-labeled ductal and periductal
      cells expanding into the liver acinus. Although the growth factors all increased
      the number of labeled cells, they preferentially acted on different cell
      populations. Although exposure to 2-AAF alone or combined with infusion of HGF
      resulted in proliferation of almost equal numbers of ductal and Ito cells,
      infusion of EGF and any combination hereof resulted in 75% to 80% of labeled
      cells having a ductal phenotype. Also, infusion of EGF and HGF resulted in
      decreased numbers of cells undergoing apoptosis in response to 2-AAF. Our results
      demonstrate that, although 2-AAF acts as a mitogenic stimulus for ductal and
      periductal cells, growth factors are necessary for survival, motility, and
      expansion of these cells into the liver acini.

PMID- 8550052
TI  - Lymphoproliferative responses to hepatitis C virus core, E1, E2, and NS3 in
      patients with chronic hepatitis C infection treated with interferon alfa.
AB  - The quality of the hepatitis C virus (HCV)-specific T-cell response may greatly
      determine the course of an HCV infection. An adequate T-cell response may
      contribute to a successful clearance of the virus and a rapid recovery from the
      disease. An inadequate response may lead to viral persistence and may eventually
      contribute to the pathogenesis of hepatocellular damage in chronic disease. The
      effect of interferon alfa (IFN-alpha), presently the most popular therapeutic
      agent for chronic HCV infections, on HCV-specific T-cell responses is completely
      unknown. To demonstrate the presence of HCV-specific T lymphocytes during chronic
      HCV infections, to know their antigenic specificities, and to examine possible
      effects of IFN-alpha treatment on their presence and antigen recognition
      patterns, we have stimulated peripheral blood mononuclear cells (PBMC) from 35
      chronic HCV patients with nine pools of synthetic peptides representing the HCV
      Core, E1, and E2 proteins as well as with a recombinant NS3 protein. The
      proliferative responses of PBMC from 16 healthy control subjects toward these
      antigens were measured for comparison. Lymphoproliferative responses of patients
      with chronic HCV infections were assayed either before (in 10 patients), during
      (in 13 patients), or after (in 21 patients) treatment with IFN-alpha. The
      analysis showed that PBMC from most HCV patients consistently recognized the COOH
      terminal part of the core protein. E1, E2, and NS3 were recognized less
      frequently. This recognition pattern was not related to the therapy with IFN
      alpha nor to the clinical response of the patient toward this therapy. The
      response to the Core protein could be fine-mapped to the COOH-terminal region
      encompassing amino acids (aa) 73 to 92, 121 to 140, 145 to 164, and 157 to 176.

PMID- 8550053
TI  - Impaired bile flow and disordered hepatic calcium homeostasis are early features
      of halothane-induced liver injury in guinea pigs.
AB  - To characterize the early events in liver injury produced by halothane,
      experiments were performed in genetically susceptible guinea pigs 19 hours after
      halothane exposure. Serum bile acid concentrations were fourfold increased in
      halothane-exposed animals compared with controls. In isolated perfused liver
      experiments, livers from halothane-exposed animals did not differ in hepatic
      oxygen uptake or in perfusion pressure at the end of experiments, but bile flow
      and biliary bile salt concentrations were reduced. Hepatic calcium content was
      increased in halothane-exposed guinea pigs compared with controls, and further
      experiments were performed to explore the reason for this. As determined by
      infusion of 45Ca to steady-state perfusate concentrations, hepatic calcium
      clearance was increased in halothane-exposed guinea pigs compared with controls
      (0.37 +/- 0.06 vs. 0.28 +/- 0.02 mL/min, P < .01). Decreased biliary excretion of
      calcium was also noted and was entirely attributable to reduced bile flow.
      However, although decreased excretion contributed to hepatic accumulation of
      calcium, it was quantitatively less important than enhanced hepatic uptake. As
      indicated by passage of a bolus of horseradish peroxidase from perfusate into
      bile, hepatic tight junction permeability was increased five-fold after halothane
      exposure. It is concluded that cholestasis, as exemplified by reduced bile flow,
      is an early feature of the liver injury produced by halothane in guinea pigs and
      is associated with increased tight junction permeability. Although the decrease
      in bile flow contributes to an early increase in hepatic calcium content, entry
      of calcium from the perfusion compartment is quantitatively more important.

PMID- 8550054
TI  - Selective inhibition of the reverse transcription of duck hepatitis B virus by
      binding of 2',3'-dideoxyguanosine 5'-triphosphate to the viral polymerase.
AB  - Hepatitis B virus (HBV) replication is mediated by the viral polymerase that
      possesses three functional domains: primer, DNA polymerase/reverse transcriptase,
      and RNase H. Using the Pekin duck as an animal model, we demonstrate a novel
      mechanism of inhibition of duck hepatitis B virus (DHBV) by 2,6-diaminopurine
      2',3'-dideoxyriboside (ddDAPR), a prodrug of 2',3'-dideoxyguanosine (ddG). A
      selective and irreversible inhibition of DHBV DNA replication is found in
      ducklings treated with high doses of ddDAPR (20 to 50 mg/kg), but not with
      similar doses of 2',3'-dideoxycytidine (ddC). The inhibition mediated by ddDAPR
      occurs at a very early stage of the reverse transcription. Despite the inhibition
      of DHBV DNA replication by ddDAPR, the DNA polymerase and reverse transcriptase
      activities of the polymerase are found to remain active when tested on exogenous
      templates in activity gels. We have demonstrated direct binding of [alpha
      32P]ddGTP to the DHBV polymerase expressed in an in vitro transcription and
      translation system. These results suggest that the binding of ddGTP to the
      polymerase blocks the initial DNA replication.

PMID- 8550055
TI  - Bacterial translocation in acute liver injury induced by D-galactosamine.
AB  - Acute liver injury is associated with a high rate of infectious and septic
      complications. Most of these infections are produced by gram negative enteric
      bacteria. We evaluated bacterial translocation, intestinal permeability, blood
      flow, portal pressure, and intestinal microflora after induction of liver injury
      and 70% liver resection in the rat. The rate of translocation to both portal and
      arterial blood was 100% at 24 hours and 50% at 48 hours after liver resection
      compared with 83% to portal vein and 50% to aortic blood at both time points
      after acute liver injury. Translocation to intraabdominal organs (liver, spleen,
      and mesenteric lymph nodes) was 100% in both groups at both 24 and 48 hours. The
      rate of translocation increased after liver injury at 48 hours with progression
      of the liver injury but was decreased in the 70% liver resection group with
      improvement of liver function. "Total aerobic" and "total anaerobic" bacterial
      counts in small intestine and cecum were not affected. Pulmonary, distal small
      intestine, and cecal blood flow were decreased in both groups, whereas blood flow
      in the proximal small intestine was unaffected. Portal pressure and flow were
      increased after 70% liver resection, but they were decreased in acute liver
      injury. After acute liver injury, permeability of both distal small intestine and
      cecum increased, but after liver resection only cecal permeability increased. The
      results of this experiment show that bacterial translocation occurs in
      experimental acute liver injury and that its dynamic, pattern and fate are
      different from that observed after liver resection, which is a reversible
      surgical model of liver insufficiency.

PMID- 8550056
TI  - A universal steady state I-V relationship for membrane current.
AB  - A purely electrical mechanism for the gating of membrane ionic channel gives rise
      to a simple I-V relationship for membrane current. Our approach is based on the
      known presence of gating charge, which is an established property of the membrane
      channel gating. The gating charge is systematically treated as a polarization of
      the channel protein which varies with the external electric field and modifies
      the effective potential through which the ions migrate in the channel. Two
      polarization effects have been considered: 1) the up or down shift of the whole
      potential function, and 2) the change in the effective electric field inside the
      channel which is due to familiar effect of the effective reduction of the
      electric field inside a dielectric body because of the presence of surface
      charges on its surface. Both effects are linear in the channel polarization. The
      ionic current is described by a steady state solution of the Nernst-Planck
      equation with the potential directly controlled by the gating charge system. The
      solution describes reasonably well the steady state and peak-current I-V
      relationships for different channels, and when applied adiabatically, explains
      the time lag between the gating charge current and the rise of the ionic current.
      The approach developed can be useful as an effective way to model the ionic
      currents in axons, cardiac cells and other excitable tissues.

PMID- 8550057
TI  - Estimating net joint torques from kinesiological data using optimal linear system
      theory.
AB  - Net joint torques (NJT) are frequently computed to provide insights into the
      motor control of dynamic biomechanical systems. An inverse dynamics approach is
      almost always used, whereby the NJT are computed from 1) kinematic measurements
      (e.g., position of the segments), 2) kinetic measurements (e.g., ground reaction
      forces) that are, in effect, constraints defining unmeasured kinematic quantities
      based on a dynamic segmental model, and 3) numerical differentiation of the
      measured kinematics to estimate velocities and accelerations that are, in effect,
      additional constraints. Due to errors in the measurements, the segmental model,
      and the differentiation process, estimated NJT rarely produce the observed
      movement in a forward simulation when the dynamics of the segmental system are
      inherently unstable (e.g., human walking). Forward dynamic simulations are,
      however, essential to studies of muscle coordination. We have developed an
      alternative approach, using the linear quadratic follower (LQF) algorithm, which
      computes the NJT such that a stable simulation of the observed movement is
      produced and the measurements are replicated as well as possible. The LQF
      algorithm does not employ constraints depending on explicit differentiation of
      the kinematic data, but rather employs those depending on specification of a cost
      function, based on quantitative assumptions about data confidence. We illustrate
      the usefulness of the LQF approach by using it to estimate NJT exerted by
      standing humans perturbed by support-surface movements. We show that unless the
      number of kinematic and force variables recorded is sufficiently high, the
      confidence that can be placed in the estimates of the NJT, obtained by any method
      (e.g., LQF, or the inverse dynamics approach), may be unsatisfactorily low.

PMID- 8550058
TI  - A less invasive Emax estimation method for weaning from cardiac assistance.
AB  - The maximum elastance of the ventricle (Emax) is a strong candidate for a
      quantitative index used for determination of the timing of weaning the patient
      from a left ventricular assist device (LVAD). This paper presents a new and less
      invasive method for deriving Emax of the left ventricle under the LVAD
      assistance. In this method (the CoP method), Emax can be calculated from two
      different end-systolic points which are produced by changing the drive phase of
      LVAD without any vascular clamping and any direct measurement of the left
      ventricular volume. Animal experiments indicated that the CoP method is useful
      when the measured left ventricular flow and pressure are employed. Moreover, a
      new technique for estimating the left ventricular flow was developed to make the
      CoP method less invasive without direct measurement of the flow. The technique
      could considerably improve the estimation accuracy of the flow in the co
      pulsation mode in comparison with the previous one proposed by the authors.
      However, it has been revealed that the estimation accuracy of the left
      ventricular flow was not globally high enough to apply the CoP method to clinical
      cases in spite of its much less invasiveness.

PMID- 8550059
TI  - A mathematical model of make and break electrical stimulation of cardiac tissue
      by a unipolar anode or cathode.
AB  - Numerical simulations of electrical stimulation of cardiac tissue using a
      unipolar extracellular electrode were performed. The bidomain model with unequal
      anisotropy ratios represented the tissue, and the Beeler-Reuter model represented
      the active membrane properties. Four types of excitation were considered: cathode
      make (CM), anode make (AM), cathode break (CB), and anode break (AB). The
      mechanisms of excitation were: for CM, tissue under the cathode was depolarized
      to threshold; for AM, tissue at a virtual cathode was depolarized to threshold;
      for CB, a long cathodal pulse produced a steady-state depolarization under the
      cathode and hyperpolarization at a virtual anode. At the end (break) of the
      pulse, the depolarization diffused into the hyperpolarized tissue, resulting in
      excitation. For AB, a long anodal pulse produced a steady-state hyperpolarization
      under the anode and depolarization at a virtual cathode. At the end (break) of
      the pulse, the depolarization diffused into the hyperpolarized tissue, resulting
      in excitation. For AB stimulation, decay of the hyperpolarization faster than
      that of the depolarization was necessary. The thresholds for rheobase and
      diastolic CM, AM, CB, and AB stimulation were 0.038, 0.41, 0.49, and 5.3 mA,
      respectively, for an electrode length of 1 mm and a surface area of 1.5 mm2.
      Threshold increased as the size of the electrode increased. The strength-duration
      curves for CM and AM were similar except when the duration was shorter than 0.2
      ms, in which case the AM threshold rose more quickly with decreasing duration
      than did the CM threshold. CM and AM resulted in similar strength-frequency
      curves. The model agrees qualitatively, but (in some cases) not quantitatively,
      with experiments.

PMID- 8550060
TI  - Threshold variability in fibers with field stimulation of excitable membranes.
AB  - The central focus of this report is the evolution of transmembrane potentials
      following initiation of a point-source field stimulus, particularly when the
      stimulus is short and the stimulating electrode is close to the fiber. The
      transmembrane voltage threshold in response to a point-source field stimulus was
      determined in a numerical model of a single unmyelinated fiber. Both nerve
      (Hodgkin-Huxley) and cardiac (Ebihara-Johnson [1]) models of the fiber membrane
      were evaluated. A central question is whether it is possible to know in advance
      whether a stimulus of specific magnitude, duration, and location will result in a
      subsequent action potential. Such determination can be based on the membrane's
      "voltage threshold." In contrast to the commonly held view, the voltage threshold
      was found to vary markedly depending on the duration and location of the field
      stimulus. Voltage thresholds ranged from about 8 mV above baseline to more than
      100 mV above baseline, the higher thresholds occurring with shorter stimuli and
      electrode locations closer to the membrane. A related question is whether the
      passive membrane response can be used as a tool in determining whether a
      subsequent action potential is elicited. If the answer is affirmative, this
      finding can be very useful, since passive properties are linear and thereby much
      simpler to evaluate than active ones. The results show that the passive response
      tracks active responses long enough to be a good estimator of subsequent action
      potential development. Examples show that the evaluation of Vm at 0.2-0.5 msec
      after stimulus initiation, times chosen on the basis of membrane characteristics,
      was a better predictor of subsequent excitation than was either initial
      transmembrane current or Vm at the time when the stimulus ends. Most of the
      circumstances analyzed here with electric field stimulation also appear likely to
      be valid with magnetic field stimulation.

PMID- 8550061
TI  - The effects of errors in assumed conductivities and geometry on numerical
      solutions to the inverse problem of electrocardiography.
AB  - In this paper we used a previously proposed model problem to examine the effects
      of inhomogeneities on four techniques for numerically solving the inverse problem
      of electrocardiography. The layered inhomogeneous eccentric spheres system
      contains three regions representing the lungs, muscle, and subcutaneous fat, and
      is numerically modeled using finite elements. We simulated both anterior and
      posterior spherical cap activation fronts. We examined inverse solutions based on
      zero order Tikhonov regularization, truncated singular value decomposition, our
      new generalized eigensystem approach, and a modification of the generalized
      eigensystem approach. The effects on the inverse solutions of geometrical errors,
      errors in the assumed conductivities, and homogeneous torso assumptions were
      examined.

PMID- 8550062
TI  - SAR optimization in a phased array radiofrequency hyperthermia system. Specific
      absorption rate.
AB  - RF deep hyperthermia systems make use of phased arrays of applicators in order to
      heat tumors selectively while maintaining healthy tissue at normal temperatures.
      A new method for the array synthesis is proposed based on the identification of
      targets to be heated (tumors) and targets to be prevented from excess
      electromagnetic radiation. The best array feed for each target is found from the
      solution of the eigenvector problem for a positive definite Hermitian matrix
      defined for that target. The optimal feed in a global sense then results from a
      trade-off of the best feeds of individual targets enforced through minimization
      of an objective function aimed at weighting the distances of the globally optimal
      feed from the feed vectors optimized for each target separately. An application
      to the heating of a pelvis is provided as an example.

PMID- 8550064
TI  - Multichannel PC-based data-acquisition system for high-resolution EEG.
AB  - This paper describes a complete, high-performance data-acquisition system for
      high-resolution EEG. The system includes preamplified EEG electrodes, rigid
      helmets, differential instrumentation and software-controlled gain amplifiers,
      digitizing and control circuitry, and optical coupling to a 486 PC. Miniaturized
      preamplifiers mounted on individual electrodes reduce coupling to external
      electromagnetic fields and minimize signal distortion caused by increased and/or
      imbalanced electrode impedances. Electrodes are applied quickly and with minimal
      skin preparation, yet with high packing densities and repositioning consistent to
      about 1-3 mm in repeated applications. Extensive testing under realistic
      conditions demonstrates that the system provides superior electrical performance
      compared to currently available commercial systems.

PMID- 8550065
TI  - Multiscale detection and analysis of the senile plaques of Alzheimer's disease.
AB  - Senile plaques (SP) are one of the characteristic neuropathologic lesions of
      Alzheimer's Disease (AD), and studies of SP cortical distribution, density
      (number of SP/mm2), and morphology are expected to lead to new information about
      the mechanism and pathogenesis of AD. We describe a digital image analysis
      procedure to detect SP, and to measure SP size, shape, and total fractional area
      in digital micrographs of silver-stained tissue sections. This histology is
      nonspecific so the program detects all the significant stained objects and a
      classifier sorts the SP from other tissue elements. SP vary greatly in size and
      form, and detection is based on multiscale template correlation. Three
      independent comparisons of computed versus expert-determined SP densities
      produced correlation coefficients greater than 0.8. The program found 94,000 SP
      in 2800 digital images of tissue sections from 42 postmortem cases including
      healthy aged controls and severely demented subjects.

PMID- 8550063
TI  - Control of high common mode voltage during transthoracic defibrillation.
AB  - A high common mode voltage (Vcm) relative to earth ground is produced on the
      myocardium during the delivery of a defibrillator pulse and can generate a
      differential error signal when potential gradients are recorded with bipolar
      electrodes and isolation amplifiers. The error signal is proportional to Vcm, and
      therefore, a reduction in Vcm improves the accuracy of the potential gradient
      data. Experiments were conducted on 5 dogs to determine whether Vcm can be
      controlled using a bridge circuit. The bridge circuit consisted of a 5 k omega
      power rheostat in parallel with the transthoracic resistance of the dog. The
      variable contact of the rheostat was connected to earth ground, and by adjusting
      the rheostat, Vcm on the myocardium could be varied. In each dog, 20 A shocks
      were delivered through stainless steel transthoracic electrodes. Point contact
      electrodes sutured to the epicardium were used to measure Vcm. It was determined
      that Vcm could be reduced to approximately zero at a given electrode on the
      heart. In addition, for the 5 dogs studied, the maximum measured Vcm on the heart
      was only 10% of the transthoracic voltage when the bridge circuit was balanced
      for an interior point in the heart.

PMID- 8550066
TI  - Alloantigen presentation by B cells: analysis of the requirement for B-cell
      activation.
AB  - This paper describes a model for investigation of the functional implications of
      B-cell activation for antigen presentation. Mixed lymphocyte cultures were used
      to assess the ability of freshly isolated B cells, mitogen-activated B cells and
      Epstein-Barr virus (EBV)-transformed B-cell lines to stimulate the activation and
      proliferation of allogeneic T cells under a variety of experimental conditions.
      It was found that resting B cells presented antigen poorly, while activated cells
      were highly immunogenic. Paraformaldehyde fixation completely eliminated antigen
      presentation by resting B cells, despite constitutive expression of class II MHC
      antigens. However, fixation had little effect on antigen presentation by
      activated B cells that expressed B7-1 and B7-2 in addition to class II major
      histocompatibility complex (MHC) molecules. Arrest of B-cell activation by serial
      fixation after treatment with F(ab')2 fragments of goat anti-human IgM produced
      cells with variable antigen-presenting capacity. Optimal antigen presentation was
      observed for cells fixed 72 hr after the initiation of B-cell activation.
      Although both B7-1 and B7-2 antigen expression increased after B-cell activation,
      it was found that the rate of T-cell proliferation correlated most closely with
      B7-2 expression. Stimulation of T cells by fixed activated B lymphocytes could be
      blocked by antibodies directed at class II MHC molecules, indicating involvement
      of the T-cell antigen receptor. In addition, T-cell proliferation was inhibited
      by antibodies specific for B7-1 and B7-2 and by the fusion protein CTLA4-Ig,
      demonstrating a requirement for CD28 signal transduction. The sole requirement of
      B7 family expression for antigen presentation by B lymphocytes was shown by
      demonstration of T-cell stimulation by fixed resting B cells in the presence of
      CD28 antibody as a source of artificial costimulation.

PMID- 8550067
TI  - T-cell dependent response to immune complexes abrogates B-cell unresponsiveness
      to pneumococcal cell wall polysaccharide.
AB  - Although > 90% of B cells from M167 (mu, kappa) immunoglobulin transgenic (Tg)
      mice express surface immunoglobulin that binds phosphorylcholine (PC), we found
      that these mice are unresponsive to immunization with pneumococcal cell wall
      polysaccharide (PnC), a type II thymus-independent antigen that contains PC.
      However, when the PnC antigen was presented as a complex with TEPC-15 or McPC-603
      antibodies (which are specific for PnC), a vigorous immune response occurred in
      which the Tg mice produced 10-50-fold more anti-PnC antibody than when immunized
      with antigen alone. Interestingly, MOPC-167, which expresses the VH and VL
      regions used to encode the transgene antibody, was found to be a relatively poor
      'carrier' for PnC, eliciting a weak anti-PnC antibody response in M167 (mu,
      kappa) Tg mice. In vivo administration of anti-CD4 antibody dramatically reduced
      the response to TEPC-15/PnC complexes, suggesting that the response is mediated
      by immunoglobulin (idiotype)-dependent helper T cells. The results indicate that
      unresponsiveness to PnC is due not to tolerance of the transgenic B cells but
      rather to the lack of T-cell help resulting from T-cell tolerance to the
      transgene-encoded idiotype.

PMID- 8550068
TI  - Mucosal memory B cells retain the ability to produce IgM antibodies 2 years after
      oral immunization.
AB  - In recent studies we have demonstrated that immunological B- and T-cell memory
      may be stimulated effectively by oral immunization, simply by admixing protein
      antigens with cholera toxin (CT) adjuvant. Here we extend information by
      employing a hapten-carrier system allowing us to separate B- and T-cell memory
      and to evaluate the requirement of memory T cells for effective reactivation of
      mucosal memory B cells. We found that 2 weeks following oral priming
      immunizations with dinitrophenyl-keyhole limpet haemocyanin (DNP-KLH) plus CT
      adjuvant, significant serum anti-DNP antibodies of IgG, IgA and IgM
      immunoglobulin classes were demonstrated. However, after 2 years only IgM anti
      DNP antibodies could still be detected in serum. When memory lymphocytes were
      isolated from these mice, from both systemic and gut-associated lymphoid tissues,
      and challenged with antigen in vitro, vigorous IgM, but no IgG or IgA, anti-DNP
      production was observed. By contrast, when the DNP-KHL-primed memory mice were
      challenged in vivo by an oral booster immunization with DNP-KLH plus CT adjuvant,
      strong systemic IgG and local mucosal IgA anti-DNP responses were recorded, while
      IgM anti-DNP production was poor. Moreover, the mucosal memory B cells from DNP
      KHL-immunized mice were more responsive in vivo to an oral booster immunization
      with the carrier-specific antigen, DNP-KLH, compared to that provided by an
      unrelated carrier, DNP-human serum albumin (HSA), which gave only poor mucosal
      and systemic anti-DNP B-cell responses. Taken together our data suggest that
      mucosal memory B cells are recirculating cells that have retained their ability
      to produce IgM antibodies and, therefore, have not undergone switch
      differentiation involving gene rearrangements with constant mu-chain deletions.
      Furthermore, mucosal B-cell memory and CD4+ T-cell memory are closely
      interconnected phenomena, requiring both components for effective expression and
      probably also for maintenance of immunological memory in the mucosal immune
      system.

PMID- 8550069
TI  - Regulation and targeting of T-cell immune responses by IgE and IgG antibodies.
AB  - A set of chimeric antibodies with identical F(ab')2 fragments specific for the
      hapten 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP), but with different human Fc
      parts (gamma 1, gamma 2, gamma 3, gamma 4, epsilon), was used to compare the role
      of IgG and IgE antibodies in antigen presentation by human Epstein-Barr virus
      (EBV) B cells. Two or three molecules of NIP were coupled to one molecule of Der
      pI (Der pI-(3)NIP), a major allergen of Dermatophagoides pteronyssinus. Both
      monomeric IgG and performed complexes of various Der pI/IgG ratios failed to bind
      significantly to the Fc receptor for IgG on B cells (Fc gamma RII; CD32). Binding
      of IgG3 (> IgG1)-containing complexes (optimal ratio of antigen to antibody =
      1:1) could be enhanced by increasing the number of haptens per Der pI molecule to
      nine or more. However, antigen presentation mediated by IgG and CD32 was not seen
      with either pulsed B cells or B cells that were allowed to capture the IgG
      complexes during the whole stimulation period. IgE binding to CD23 and subsequent
      IgE-mediated antigen presentation was seen under all conditions tested. Even
      monomeric immune complexes (IC) (Der pI-(3)NIP/IgE), in the absence of CD23 cross
      linking, induced an immune response. As the number of natural epitopes for human
      antibodies on Der pI was less than five, we conclude that, in vivo, complexes
      consisting of Der pI/IgG will be directed to antigen-presenting cells expressing
      the high-affinity receptor for IgG (CD64), whereas IgE will allow antigen
      presentation by CD23-expressing cells, including B cells.

PMID- 8550070
TI  - T-cell-independent and T-cell-dependent IgE responses to the nematode
      Nippostrongylus brasiliensis: comparison of serum IgE and mast-cell-bound IgE.
AB  - The IgE immune response was studied in female athymic, nude (Lewis rnu/rnu) and
      euthymic (Lewis +/+) rats infected with the nematode Nippostrongylus
      brasiliensis. During the course of the infection, serum IgE levels were followed
      using an enzyme-linked immunosorbent assay technique (ELISA), while the surface
      expression and occupancy of IgE receptors on peritoneal mast cells were
      quantified using flow cytometry after immunolabelling with anti-IgE. The results
      show that the up-regulation of IgE receptors, which takes place on the mast cells
      of both athymic and normal rats during the early phase of the immune response, is
      more pronounced and longer-lasting in normal rats than in athymic ones, thereby
      suggesting that T cells are necessary for a full response to the parasite
      infection. The increased IgE occupancy observed on the mast cells during the
      early phase of the parasite immune response was not reflected in the serum IgE
      levels, which remained low during the entire infection period in athymic rats. In
      euthymic rats, on the other hand, there was a pronounced increase in serum IgE,
      as well as an increase in IgE occupancy on the mast cells, all reaching a peak
      level after 2 weeks of infection. However, there was no significant correlation
      between the serum IgE concentration and IgE occupancy or the density of IgE
      receptors on the mast cells of the individual euthymic rats. This indicates that
      the quantification of IgE occupancy on the mast cells may be a better way of
      detecting low-level IgE responses than the measurement of serum IgE. These
      findings, which were obtained in female Lewis rats, when compared with our
      previous findings in male rats of the same strain, suggest that sex differences
      may exist in terms of the intensity and duration of the IgE immune response to
      the parasite infection.

PMID- 8550071
TI  - Gangliosides are potent immunosuppressors of IL-2-mediated T-cell proliferation
      in a low protein environment.
AB  - Gangliosides are immunosuppressive to many classes of immune cells, and shedding
      of these glycosphingolipids by tumour cells may regulate immune responses in
      cancer, and protect tumours from host immune destruction. One mechanism of
      immunosuppression by gangliosides in vitro involves competition with interleukin
      2 receptors (IL-2R) for binding of IL-2. Previous studies on inhibition of IL-2
      mediated events by gangliosides have been conducted in the presence of high
      levels of fetal bovine serum (FBS). However, gangliosides shed by tumours in vivo
      will encounter immune cells in the low protein microenvironment of the tissue
      fluid. In order to better mimic physiological conditions, we have examined
      immunosuppression by gangliosides towards IL-2-dependent HT-2 cells in a low
      serum-low protein medium. The ability of gangliosides to inhibit IL-2-stimulated
      DNA synthesis in HT-2 increased dramatically as the serum concentration in the
      culture medium was decreased; the 50% inhibitory concentration (IC50) value for
      GM1 was 13 microM under low serum conditions, 14-fold lower than the value
      obtained in 10% FBS. Further investigation revealed that the mechanism of
      immunosuppression by gangliosides in low serum-low protein medium involved
      interference with the IL-2/IL-2R system. Ganglioside-mediated inhibition was
      dependent on the continued presence of the glycolipids during the first few hours
      after IL-2 stimulation, and could be reversed by increasing levels of IL-2.
      Receptor binding experiments demonstrated that gangliosides blocked the
      interaction of IL-2 with high-affinity IL-2 receptors on HT-2. Taken together,
      these results support the view that gangliosides will act as much more potent
      suppressors of IL-2-dependent processes in vivo in the vicinity of a tumour.

PMID- 8550072
TI  - High-level IL-10 production by monoclonal antibody-stimulated human T cells.
AB  - We investigated interleukin-10 (IL-10) production in freshly isolated mononuclear
      cells and purified T cells in response to stimulation with monoclonal antibodies
      (mAb) recognizing CD3, CD2 and CD28, or with the bacterial products
      Staphylococcus aureus cells (SAC), staphylococcal enterotoxin (SEA) and
      lipopolysaccharide (LPS). IL-10 production was compared with that of IL-2, IL-4
      and interferon-gamma (IFN-gamma). Similar to the other cytokines, in peripheral
      blood mononuclear cells (PBMC) from adult donors the highest IL-10 levels were
      produced in response to CD2 plus CD28 stimulation, within 72-96 hr of
      stimulation. Levels of IL-10 in response to CD2 plus CD28 stimulation (1.9 +/- 1
      ng/ml) exceeded those in response to SEA (0.25 +/- 0.16 ng/ml), SAC (0.43 +/-
      0.42 ng/ml), or LPS (0.19 +/- 0.14 ng/ml) stimulation. With adult purified T
      cells, high levels of IL-10 and IL-4 were measured following CD3 plus CD28
      stimulation, and the amounts of both T-helper type-2 (Th2) cytokines decreased
      following the addition of phorbol myristate acetate (PMA), whereas the synthesis
      of the Th1 cytokines IL-2 and IFN-gamma was enhanced. When PBMC were stimulated
      with a CD3 mAb and different other cytokines were added, strong enhancement of IL
      10 production was seen upon the addition of IL-2, IL-4, IL-7, IL-12 and IFN
      gamma, whereas inhibition was found with transforming growth factor-beta 1 (TGF
      beta 1). These data illustrate that in freshly isolated PBMC large amounts of IL
      10 can be induced rapidly by appropriate mAb stimulation, and that even in
      freshly isolated cells IL-4 and IL-10 show signs of parallel regulation.

PMID- 8550073
TI  - Development and antigen specificity of the lymphoproliferation responses of pigs
      to pseudorabies virus: dichotomy between secondary B- and T-cell responses.
AB  - To better understand the contribution of T cells to the immunity of pigs to
      pseudorabies virus (PRV), we examined the lymphoproliferation response to this
      virus. Depletion studies demonstrated that both CD2+CD8+ and CD2+CD4+ cells
      contributed to lymphoproliferation, but to varying degrees upon stimulation with
      live and ultraviolet (UV) light-inactivated PRV. Flow cytometric analysis
      revealed the emergence of both CD2+CD8+ and CD2+CD4+ lymphoblastoid cells. To
      examine the contribution of specific viral proteins, we prepared immortalized
      porcine B cells of haplotype d/d that stably expressed a single PRV protein, and
      used these cells for in vitro stimulation of lymphocytes from PRV-immune
      miniature pigs of the same haplotype. Cells expressing PRV gB or gC induced
      proliferation. An immunization/challenge experiment showed that the
      lymphoproliferation response was stronger upon immunization with the virulent NIA
      3 strain than with the attenuated Bartha strain. Upon challenge inoculation, the
      NIA-3-immunized pigs were almost completely immune, in contrast to the Bartha
      immunized pigs. Such poorly protected pigs showed secondary B- and T-cell immune
      responses upon challenge. In contrast, the better protected NIA-3-immunized pigs
      did not show a secondary B-cell response. However, they developed a secondary
      lymphoproliferation response, which was quicker and stronger than in the Bartha
      immunized pigs. This dichotomy between secondary B- and T-cell responses
      indicates that an effective T-cell memory response is able to quickly eliminate
      challenge virus in immune pigs, so preventing a secondary B-cell response.

PMID- 8550074
TI  - IL-4 is able to reverse the CD2-mediated negative apoptotic signal to CD4-CD8-
      alpha beta and/or gamma delta T lymphocytes.
AB  - Activation of immature thymocytes or transformed T lymphocytes via T-cell
      receptor (TCR)/CD3 signalling can induce programmed cell death (apoptosis).
      Recent data indicate that anti-CD3/TCR monoclonal antibodies (mAb) also trigger
      apoptosis in activated (but not resting) mature peripheral blood T lymphocytes.
      Here we report that triggering of resting CD4-CD8-TCR alpha beta+ and/or TCR
      gamma delta+ via the alternative CD2-dependent activation pathway is able to
      induce programmed cell death. A pair of mitogenic anti-CD2 mAb provoked a
      dramatic rise in [Ca2+]i that was almost entirely sustained by extracellular
      fluxes, and the inhibition of membrane [Ca2+/Mg2+] ATPase. The resulting
      endonuclease activation was able to induce DNA fragmentation, as revealed by
      propidium iodide staining and gel electrophoresis. Induction of apoptosis was
      prevented by the presence of interleukin-4 (IL-4) as well as by endonuclease
      inactivation with 100 microM ZnCl2, but enhanced by the contemporary block of
      protein kinase C. Thus it seems that in resting T lymphocytes the strong calcium
      signal delivered by the alternative CD2 activation pathway may act as a negative
      apoptotic signal in both alpha beta and gamma delta T cells with low (non-major
      histocompatibility complex restricted) antigenic affinity, so limiting the
      extension of polyclonal T-cell growth.

PMID- 8550075
TI  - T-cell receptor usage of interleukin-2-responsive peripheral gamma delta T cells.
AB  - The majority of human peripheral gamma delta T cells express the V gamma 9 gene
      in combination with the V delta 2 gene. The diversity of this subset of gamma
      delta T cells is limited by a preferential usage of the J gamma P gene segment
      and a highly distinctive junctional motif of the T-cell receptor (TCR) delta
      chain. We and others have observed that peripheral blood derived V gamma 9+V
      delta 2+ gamma delta T cells of healthy individuals are activated after
      stimulation with interleukin-2 (IL-2) in vitro, but only a small percentage of
      gamma delta T cells subsequently proliferates. To assess whether the
      proliferating, IL-2-responsive gamma delta T cells represent a selective group of
      T cells, we have analysed TCR junctional features of IL-2-responsive gamma delta
      T cells. Out of 30 individuals studied, nine were identified as IL-2-responders
      and three as IL-2-hyperresponders. The TCR V(D)J gene usage from IL-2 stimulated
      peripheral blood lymphocytes of these IL-2-(hyper)responsive individuals was
      analysed. The results showed that in most individuals gamma delta T cells
      polyclonally expanded after stimulation with IL-2. In two IL-2-hyperresponder
      individuals, however, a monoclonal expansion of a particular V gamma 9+V delta 2+
      gamma delta T cell was found. In one of these individuals, this V gamma 9+V delta
      2+ T-cell clone expressed a very rare gamma delta TCR type because of the
      presence of an Ala within the junctional region at a conserved position relative
      to V delta framework residues (delta 97), which is very infrequently used by
      peripheral blood V gamma 9+V delta 2+ cells. This particular clonotype could also
      be detected in unstimulated PBL samples taken from that individual, and made up
      for 30% of the total peripheral gamma delta T-cell pool. These data indicate that
      in general IL-2-responsive V gamma 9+V delta 2+ gamma delta T cells represent a
      polyclonal population, reflecting in vivo stimulation with multiple antigens or
      superantigens. In contrast, monoclonal expansions of gamma delta T cells after
      stimulation with IL-2 can also occur, which may be related to an in vivo
      stimulation by one particular antigen, rendering this gamma delta T-cell type
      dominant in the peripheral blood.

PMID- 8550076
TI  - Expression of recombinant soluble Fc epsilon RI: function and tissue distribution
      studies.
AB  - Recombinant soluble IgE Fc receptors (rsFc epsilon RI) are potent inhibitors of
      type I hypersensitivity reactions tested in a local inflammatory setting.
      However, the fate of these receptors in vivo is dependent on the cellular source
      of the rsFc epsilon RI. We have produced these by transiently transfecting Cos-7
      cells with a cDNA encoding the extracellular domains of human Fc epsilon RI alpha
      chain. Following affinity purification, the rsFc epsilon RI was characterized as
      58,000 MW, which was reduced to 23,000 MW following endoglycosidase F treatment.
      The purified rsFc epsilon RI could inhibit mouse IgE binding to Fc epsilon RI+
      transfected CHO-K1 cells in vitro, bind sIgE+ B lymphoma cells in vitro, and
      inhibit the passive cutaneous anaphylaxis model in vivo in Sprague-Dawley rats.
      Pharmacokinetic studies in vivo involving intravenous injection of radiolabelled
      rsFc epsilon RI in mice revealed the receptor to have a rapid initial blood
      clearance (t1/2 early phase of 15 min) and to accumulate in the liver before
      being detected in urine. The localization of rsFc epsilon RI in the liver could
      be blocked by administration of mannose glycosylated ovalbumin and mannan,
      demonstrating that liver uptake involved the mannose receptor that is expressed
      on liver sinusoid cells and Kupffer cells. The production of rsFc epsilon RI
      using a stable expression system in CHO-K1 cells produced functional receptor of
      the same molecular weight as the Cos-7 system by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE). However, biodistribution studies
      demonstrated differences; the CHO-K1 cell-produced material did not localize to
      the liver in comparison to the Cos-7-produced rsFc epsilon RI.

PMID- 8550077
TI  - Expression of different lipoprotein receptors in natural killer cells and their
      effect on natural killer proliferative and cytotoxic activity.
AB  - Natural killer (NK) cells take up chylomicrons (CM), very low density (VLDL), low
      density (LDL), high density (HDL) and acetyl-modified low density (AcLDL)
      lipoproteins through different receptors, VLDL being the lipoprotein with the
      highest uptake and HDL the lowest. The uptake of LDL can be selectively blocked
      by the anti-LDL receptor, which does not affect the uptake of CM, VLDL, HDL and
      AcLDL. Although the uptake of lipoproteins assessed by flow cytometry using DiI
      is not very high, the lipoproteins are able to induce an increase in
      proliferative responses, VLDL, AcLDL and HDL being the most important ones with
      12- and 17-fold increments, respectively. CM, VLDL and LDL at low concentrations
      increase NK cytotoxic activity, while HDL and AcLDL inhibit, in a dose-dependent
      fashion, the killing of NK cells against K562. These results suggest the presence
      of four different receptors that are responsible for the cytotoxic and
      proliferative responses observed.

PMID- 8550078
TI  - Lymphocyte adhesion and transendothelial migration in the central nervous system:
      the role of LFA-1, ICAM-1, VLA-4 and VCAM-1. off.
AB  - Lymphocyte adhesion to and migration across endothelial cell (EC) monolayers,
      derived from the rat blood-retinal barrier (BRB), were measured in vitro. The
      binding of concanavalin A (Con A)-activated peripheral lymph node lymphocytes and
      the migration of CD4+ T-cell lines could be significantly increased by treating
      the EC with interleukin-1 beta (IL-1 beta). To determine the role of various
      adhesion molecules during the processes of lymphocyte binding and transmonolayer
      migration (diapedesis), lymphocytes were treated with monoclonal antibody (mAb)
      specific for CD11a (alpha L subunit of leucocyte functional antigen-1; LFA-1),
      CD18 (beta 2 subunit of leucam family) and CD49d (alpha 4 subunit of very late
      activation antigen-4; VLA-4) and EC with mAb specific for CD54 (intercellular
      adhesion molecule-1; ICAM-1) and CD106 (vascular cell adhesion molecule-1; VCAM
      1). Binding of the highly adhesive but non-migratory Con A-activated lymphocytes
      was inhibited by mAb to CD11a (reduced to 73% and 65% of control lymphocyte
      adhesion) and CD18 (42% and 54%) on non-activated and IL-1 beta-treated EC,
      respectively, but not by mAb to ICAM-1 or VCAM-1. Diapedesis of the highly
      migratory T-cell line lymphocytes was also blocked by antibodies to CD11a
      (reduced to 11% and 10% of control T-cell migration), CD18 (29% and 43%) but in
      addition was also inhibited by anti-ICAM-1 (17% and 53%) on non-activated and IL
      1 beta treated EC, respectively. Both anti-VLA-4 and anti-VCAM-1 were also
      effective in producing a smaller reduction in migration, but only on IL-1 beta
      activated EC (66% and 58% of control migration, respectively). These studies
      indicate that lymphocyte adhesion to central nervous system (CNS) vascular EC is
      largely dependent on LFA-1 but not through its interaction with ICAM-1. In
      contrast, lymphocyte diapedesis is mostly supported through the LFA-1/ICAM-1
      pairing, with a small proportion being mediated by VLA-4/VCAM-1 on IL-1 beta
      activated EC. This latter pathway, however, also appears to be dependent on LFA-1
      interacting with the EC.

PMID- 8550079
TI  - Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in
      vitro.
AB  - Chlorpromazine (CPZ) has been previously shown to protect against endotoxin
      [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis
      factor in vivo. We investigated at the cellular level whether this was due to
      direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using
      LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect
      of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse
      fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP
      1 cells in a dose dependent manner by a maximum of 80%. This effect was
      comparable to that of two well-known inhibitory drugs, dexamethasone and
      cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ
      (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the
      cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could
      provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis
      in L929 cells, as detected by analysis of nuclear morphology. However, since we
      showed that apoptosis was very limited, and was not the main mode of cell death
      in our conditions, this could not explain the overall protection. Since CPZ did
      not interfere with either the oligomerization state of TNF-alpha or its receptor
      binding, our data suggest that it reduced cytotoxicity by inhibiting some steps
      in the TNF-alpha signalling pathways.

PMID- 8550080
TI  - Production of type-1 and type-2 cytokines by peripheral blood mononuclear cells
      of psoriatic patients.
AB  - We investigated the function of peripheral blood mononuclear cells (PBMC) in 16
      patients with active psoriasis, in 15 patients with static psoriasis and in 27
      healthy volunteers, by examining in vitro proliferation and antigen- and mitogen
      stimulated production of interleukin-2 (IL-2) and IL-4. Plasma levels of the
      neuropeptide substance P were also determined. Defective alloantigen (ALLO)- and
      phytohaemagglutinin (PHA)-stimulated IL-2 production was detected in 42% and in
      45% of psoriatic patients, respectively. The number of defective IL-2 responders
      was higher in static (60%) than in active (25%) psoriasis. The reduction of IL-2
      responses in the former group was associated with an increase of IL-4 production.
      Thus PBMC of 66% of patients with static psoriasis but none of the patients with
      active psoriasis produced elevated amounts of PHA-stimulated IL-4. Variations of
      plasma substance P levels followed the same pattern of IL-4, being higher in
      static than in active psoriasis. These observations suggest a co-ordinated action
      of IL-4 and substance P as modulators of the clinical course of psoriasis. Our
      data show a possible correlation between the clinical evolution of psoriasis and
      the production of type-1 and type-2 cytokines, suggesting that the former may
      have a prominent role in the activation of psoriasis, while the latter may play a
      protective role.

PMID- 8550082
TI  - Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H]5HT
      release.
AB  - Monocyte chemotactic protein-1 (MCP-1) and MCP-3, the most active and
      representative compounds of the CC chemokine family, are proinflammatory
      cytokines that attract and activate specific types of leucocytes. We have used
      highly purified isolated rat peritoneal mast cells (RPMC) cultured for different
      lengths of time with and without MCP-1 (200, 100, 50 and 25 nM). Our data clearly
      show that MCP-1 (200 nM) causes a marked release of [3H]serotonin ([3H]5HT and
      histamine, which reach a peak at 40 min of incubation (56.6 +/- 5.3 and 34.7 +/-
      6 above the control, respectively). In dose-response experiments, MCP-1 (200,
      100, 50, 25, 12.5, 6.25 and 3.12 nM) provoked a dose-dependent release of [3H]5HT
      and histamine from RPMC, which was maximum at 200 nM. After preparation of the
      histidine decarboxylase (HDC) probe, a Northern blot analysis was determined for
      HDC mRNA. After 4 hr, steady-state levels of HDC mRNA were induced in a dose
      dependent manner by MCP-1 (200-25 nM), compared to the controls. However, MCP-1
      failed to prime RPMC in [3H]5HT and histamine release when C48/80 (0.05
      micrograms/ml) or anti-IgE was used. In contrast, murine interleukin-3 (IL-3) in
      combination with MCP-1 (200 and 100 nM) provoked a greater release of histamine
      and [3H]5HT than the compounds alone. Moreover, RPMC treated with MCP-1 (200 nM)
      showed, under light microscopy (20x), greater clump formation, a phenomenon
      absent in the controls (untreated cells). The electron microscope studies
      revealed that treatment with MCP-1 (200 nM) promoted binding of RPMC and clearly
      demonstrated a communication between the cytoplasms of adjacent mast cells. Our
      report describes additional biological activities for MCP-1, suggesting for the
      first time that this human monocyte chemoattractant plays a fundamental role in
      histamine and serotonin release and cell aggregation in rat peritoneal mast
      cells.

PMID- 8550081
TI  - Stem-cell factor, the kit ligand, induces direct degranulation of rat peritoneal
      mast cells in vitro and in vivo: dependence of the in vitro effect on period of
      culture and comparisons of stem-cell factor with other mast cell-activating
      agents.
AB  - We report that stem-cell factor (SCF), the ligand of the receptor encoded by the
      c-kit proto-oncogene, is a potent activator of degranulation of rat peritoneal
      mast cells in vitro and in vivo. Freshly isolated, purified mast cells were
      relatively unresponsive to SCF (4-500 ng/ml) but progressively acquired
      responsiveness to this agent, assessed as serotonin (5-HT) release, during 48 hr
      culture in vitro. The cells showed a similar kinetic pattern of acquisition of
      responsiveness to anti-IgE but responded fully to calcium ionophore A23187 or
      compound 48/80 regardless of time in culture. Acquisition of mast cell
      responsiveness to SCF or anti-IgE was not due to serum factors or to recovery
      from the Percoll purification procedure. During culture, mast cell expression of
      the SCF receptor (SCFR) increased, and this may explain in part the increased
      responsiveness to SCF. However, surface IgE expression remained constant, and the
      increased responses to anti-IgE therefore must reflect changes in components of
      the secretion-coupling pathway that are activated subsequent to IgE cross
      linking. The unresponsiveness of freshly isolated peritoneal mast cells to SCF or
      anti-IgE does not reflect a state of in vivo unresponsiveness, as peritoneal mast
      cells degranulated in vivo in response to these agents. We conclude that in terms
      of their responsiveness to SCF or anti-IgE, cultured tissue mast cells may be
      more representative than freshly isolated mast cells of secretory function in
      vivo, and therefore may be more appropriate for physiological or pharmacological
      studies of SCF- or IgE-dependent secretory responses.

PMID- 8550083
TI  - Identification of dendritic cells as a major source of interleukin-6 in draining
      lymph nodes following skin sensitization of mice.
AB  - Skin sensitization with chemical allergens is associated with the activation and
      proliferation of T lymphocytes within lymph nodes draining the site of exposure.
      These events are accompanied by the secretion of interleukin-6 (IL-6) by lymph
      node cells (LNC). We have investigated the cellular source of IL-6 seventy-two
      hours following primary exposure of mice to the contact allergen oxazolone.
      Immunocytochemical analyses of sections of activated lymph nodes have revealed
      that cells expressing IL-6 are located within the T-dependent lymph node
      paracortex, with none present in lymphoid follicles. Cells which expressed IL-6
      cofractionated exclusively with LNC of low buoyant density, the majority of which
      also expressed membrane Ia and had a dendritic morphology. Depletion of dendritic
      cells from LNC culture was associated with a significant decrease in the
      secretion of IL-6 by the residual population. These data demonstrate that
      dendritic cells are a major source of IL-6 within lymph nodes during primary
      immune responses to cutaneous antigens.

PMID- 8550084
TI  - Bone marrow-derived chimerism in non-irradiated, cyclosporin-treated rats
      receiving microvascularized limb transplants: evidence for donor-derived
      dendritic cells in recipient lymphoid tissues.
AB  - Tolerance to donor transplantation antigens develops when recipients are made
      chimeric with donor bone marrow. To establish chimerism, the haemopoietic system
      of recipients typically is severely compromised. We report on a system in which
      chimerism develops without ablative therapies. Immunosuppression with cyclosporin
      A allowed the lower limb of a rat to be replaced by a microvascularized
      transplant from a fully allogeneic donor. Many donor-derived cells populated
      recipient lymph nodes and spleen, and most had the large size, irregular shape
      and strong major histocompatibility complex (MHC) class II expression that typify
      dendritic cells. Donor cells were not found in the macrophage-rich regions of
      lymphoid tissues, but instead occupied splenic white pulp and lymph node cortex.
      The donor cells were derived from radiosensitive marrow precursors, as chimerism
      was abolished if the grafted limb was irradiated, or if muscle and skin flaps
      devoid of bone were grafted. Donor cells were rare or not detectable in blood,
      thymus and liver. Whereas lymphoid chimerism was prominent following limb
      transfer, donor cells were not detected 1-2 weeks after an injection of two femur
      equivalents of a marrow suspension. We suggest that dendritic cells that undergo
      rapid turnover in lymphoid organs are replaced from allogeneic precursors in bone
      grafts. The combination of cyclosporin and vascularized bone provides a means for
      inducing chimerism in lymphoid tissues of non-irradiated recipients.

PMID- 8550085
TI  - Immunomodulation by cells of mononuclear phagocyte lineage in acute cold-stressed
      or cold-acclimatized mice.
AB  - Immunoregulatory states in acute cold-stressed or cold-acclimatized mice were
      investigated. When male C57BL/6 mice were exposed to environmental temperature of
      5 degrees for 24 hr (acute cold stress), the spleen cells showed depressed
      proliferative responses to stimulation with concanavalin A (Con A) or
      lipopolysaccharide (LPS) compared with control mice (reared at 25 degrees). The
      proportion of Thy-1.2+ cells increased significantly in spleens from these acute
      cold-stressed mice. The Con A responses of T-enriched cells from acute cold
      stressed mice were restored to the normal level by adding plastic-adherent cells
      from control mice. Further, adherent cells from acute cold-stressed mice markedly
      suppressed the Con A responses of control spleen cells. Thus, the plastic
      adherent cells appeared to be responsible for the suppressed Con A responses. On
      the other hand, proliferative responses to Con A or LPS were elevated in spleen
      cells from mice exposed to 5 degrees for 3 weeks (cold acclimatization). A
      significant decrease of Thy-1.2+ cells was detected in these spleens. It was
      shown that the enhanced proliferative responses were attributable to functional
      alterations of the plastic adherent cell population but not to those of lymphoid
      cell population. These findings indicate that the low or high responsiveness of
      spleen cells to Con A observed in cold-stressed or cold-acclimatized mice,
      respectively, may be due to a mechanism including the contrary modulations of
      functions of cells of mononuclear phagocyte lineage.

PMID- 8550086
TI  - Up-regulation of cytokine mRNA in human monocytes and myeloid cell lines by the
      differentiation/activation factor p48.
AB  - Polypeptide 48 is a 48,000 MW protein, originally isolated from conditioned media
      of some human leukaemic cell lines, that induces differentiation and cytolytic
      activity in HL-60 promyelocytic leukaemia cells and activates human peripheral
      blood monocytes to secrete interleukin-1 (IL-1) and tumour necrosis factor-alpha
      (TNF-alpha). In the present study we examined the effects of p48 on the
      accumulation of a series of monokine transcripts, including TNF-alpha, IL-1
      alpha, IL-1 beta and IL-6, in human peripheral blood monocytes and the
      myeloid/monocyte cell lines HL-60 and U937. Using reverse transcriptase
      polymerase chain reaction (RT-PCR) and Northern blot analysis, p48 was found to
      induce accumulation of TNF-alpha, IL-1 alpha and IL-1 beta mRNA in peripheral
      blood monocytes, HL-60 and U937 cells. IL-6 mRNA was found to be increased in p48
      stimulated peripheral blood monocytes but not HL-60 or U937. Thus, the secretion
      of IL-1 and TNF-alpha by p48-stimulated monocytic cells was associated with up
      regulation of cytokine mRNA, suggesting that p48 leads to increased transcription
      or mRNA stability in these cells. As U937 and HL-60 are likely to represent
      premonocyte stages of haemopoietic differentiation, it is possible that the
      effect of p48 on IL-6 mRNA, in contrast to its effect on TNF and IL-1, requires
      cells to be at a later differentiation step.

PMID- 8550087
TI  - Cellular distribution of proteasome subunit Lmp7 mRNA and protein in human
      placentas.
AB  - Human leucocyte antigen (HLA) class I antigen expression is closely controlled in
      placental trophoblast cells, which interface directly with genetically disparate
      maternal blood and tissues during pregnancy. In this study, the possibility that
      LMP7, a proteasome component that may be required for processing of class I
      associated peptides, might be lacking or refractory to cytokine induction in
      trophoblast cells that fail to display HLA class I antigens was investigated.
      Analysis of Lmp7 mRNA and protein in paraformaldehyde-fixed placentas by in situ
      hybridization and immunohistochemistry revealed that both HLA class I-positive
      and HLA class I-negative trophoblast cells contain Lmp7 gene products. Consistent
      with these results, northern blot hybridization studies showed that HLA class I
      positive (JEG-3) and HLA null (Jar) trophoblast-derived cell lines contain Lmp7
      mRNA. After 48 hr of exposure to HLA class I-modulating cytokines, Lmp7 mRNA
      levels in JEG-3 cells were markedly increased by two interferons (IFN-beta, IFN
      gamma) and tumour necrosis factor (TNF) whereas at the same time point, Jar cell
      Lmp7 mRNA was modestly enhanced by IFN-gamma. Collectively, the findings indicate
      that expression of HLA class I antigens in trophoblast cells is unlikely to be
      restricted by lack of Lmp7 gene products and suggest that endogenous placental
      cytokines may have different influences on Lmp7 mRNA levels in phenotypically
      distinct trophoblast subpopulations.

PMID- 8550088
TI  - Cloning and characterization of the cDNA encoding guinea-pig properdin: a
      comparison of properdin from three species.
AB  - The cDNA sequence encoding properdin was generated from guinea-pig spleen RNA by
      the reverse transcription-polymerase chain reaction. This sequence was
      approximately 75% homologous with human and 71% homologous with murine properdin
      at the nucleic acid level. Guinea-pig properdin had six thrombospondin repeat
      sequences consisting of about 60 amino acids, each with six cysteine and three
      tryptophan residues. Additionally, the Valine-Threonine-Cysteine-Glycine
      sequence, reported to have important cell adhesive properties in malarial
      circumsporozoite proteins and thrombospondin, was conserved in the properdin
      sequence of guinea-pigs. Finally, mouse spleen was also examined to complete the
      sequence determination of the leader peptide and the initial four residues of
      murine properdin. This allowed a thorough comparison of the primary structure of
      properdin from all three species. Like human and murine properdin cDNAs, the
      guinea pig sequence contained a region of unique, non-homologous sequence (18
      base pairs in length) within the fifth thrombospondin repeat, the significance of
      which remains unclear.

PMID- 8550089
TI  - Partial characterization of a circulating tolerogenic moiety which, after a feed
      of ovalbumin, suppresses delayed-type hypersensitivity in recipient mice.
AB  - Serum collected 60 min after feeding ovalbumin (OVA) to BALB/c mice transfers
      specific tolerance to naive recipients via an unknown mechanism. We have now
      identified a large fragment of the OVA molecule as the putative active moiety.
      Specific absorption of immunoreactive OVA from tolerogenic serum by
      immunoaffinity chromatography removed the tolerogenic activity; following elution
      of the bound OVA and subsequent injection into naive recipients it was possible
      to demonstrate tolerogenic activity equivalent to that seen with unmanipulated
      serum. Passage of OVA tolerogenic serum through a bovine serum albumin (BSA)
      specific affinity column had no effect on in vivo OVA tolerogenic activity.
      Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      immunoblotting using anti-OVA antibodies demonstrated the presence of two bands
      with apparent molecular weights (MW) of 21,000 and 24,000 in the OVA-related
      material absorbed from the tolerogenic serum. The 24,000 MW moiety was also
      visualized by silver staining. These moieties are putative candidate tolerogens
      as they were absent from normal BALB/c mouse serum analysed 5 min after feeding
      OVA and from severe combined immunodeficiency (SCID) mouse serum--without
      tolerising activity--analysed 60 min after a similar feed.

PMID- 8550090
TI  - Analysis of variable region genes encoding anti-Sm and anti-cardiolipin
      antibodies from a systemic lupus erythematosus patient.
AB  - We have analysed the heavy and light chain variable region genes of two
      monoclonal antibodies, specific for the Sm antigen (RSP1; IgG kappa) and for
      cardiolipin (RSP4; IgM lambda), derived from a patient with active systemic lupus
      erythematosus (SLE). We have established that the variable region genes of the
      RSP1 autoantibody are somatic mutants of two germ line genes from the VH4 and V
      kappa 1 gene families. RSP4 antibody uses gene segments closely related to a VH3
      gene member and to a V lambda 1 gene. The presence and distribution of the
      somatic mutations on both monoclonal autoantibodies are compatible with an
      antigen-driven immune process. These data suggest that in SLE a common antigenic
      stimulus may govern the autoantibody response against a wide spectrum of
      unrelated antigens, including native DNA, cardiolipin or Sm antigens, and provide
      further evidence that disease-associated autoantibodies are generated through
      antigen-selected somatic mutations.

PMID- 8550091
TI  - Nomenclature for T-cell receptor (TCR) gene segments of the immune system. WHO
      IUIS Nomenclature Sub-Committee on TCR Designation.

PMID- 8550094
TI  - Comparison of human and mouse T-cell receptor variable gene segment subfamilies.
AB  - Like the immunoglobulin Igh-V and Igk-V gene families, the human or mouse TCRV
      gene families may be grouped into subfamilies displaying > 75% nucleic acid
      sequence similarity among their members. Systematic interspecies sequence
      comparisons reveal that most mouse Tcr-V subfamilies exhibit clear homology to
      human TCRV subfamilies (> 60% amino acid sequence similarity). Homologous pairs
      of TCRV genes in mice and humans show higher sequence similarity than TCRV genes
      from different subfamilies within either species, indicating transspecies
      evolution of TCRV genes. Mouse and human homologues show conservation of their
      relative map order, particularly in the 3' region and a similar sequential and
      developmentally programmed expression. When the V regions from both species were
      analyzed together, local length differences and conserved residues in the loop
      regions were revealed, characteristic of each of the four TCRV families.

PMID- 8550092
TI  - Human T-cell receptor variable gene segment families.
AB  - Multiple DNA and protein sequence alignments have been constructed for the human
      T-cell receptor alpha/delta, beta, and gamma (TCRA/D, B, and G) variable (V) gene
      segments. The traditional classification into subfamilies was confirmed using a
      much larger pool of sequences. For each sequence, a name was derived which
      complies with the standard nomenclature. The traditional numbering of V gene
      segments in the order of their discovery was continued and changed when in
      conflict with names of other segments. By discriminating between alleles at the
      same locus versus genes from different loci, we were able to reduce the number of
      more than 150 different TCRBV sequences in the database to a repertoire of only
      47 functional TCRBV gene segments. An extension of this analysis to the over 100
      TCRAV sequences results in a predicted repertoire of 42 functional TCRAV gene
      segments. Our alignment revealed two residues that distinguish between the highly
      homologous V delta and V alpha, one at a site that in VH contacts the constant
      region, the other at the interface between immunoglobulin VH and VL. This site
      may be responsible for restricted pairing between certain V delta and V gamma
      chains. On the other hand, V beta and V gamma appear to be related by the fact
      that their CDR2 length is increased by four residues as compared with that of V
      alpha/delta peptides.

PMID- 8550093
TI  - Mouse T-cell receptor variable gene segment families.
AB  - All mouse T-cell receptor alpha/delta, beta, and gamma variable (Tcra/d-, b-, and
      g-V) gene segments were aligned to compare the sequences with one another, to
      group them into subfamilies, and to derive a name which complies with the
      standard nomenclature. It was necessary to change the names of some V gene
      segments because they conflicted with those of other segments. The traditional
      classification into subfamilies was re-evaluated using a much larger pool of
      sequences. In the mouse, most V gene segments can be grouped into subfamilies of
      closely related genes with significantly less similarity between different
      subfamilies.

PMID- 8550095
TI  - Evolutionary origins of retroposon lineages of Mhc class II Ab alleles.
AB  - Major histocompatibility complex (Mhc) class II Ab genes have evolved into three
      distinct lineages. While lineage 2 alleles differ from lineage 1 alleles by the
      insertion of a retroposon in intron 2, the basis for the extremely large intron 2
      in lineage 3 alleles has heretofore been undetermined. In this report, we
      demonstrate by nucleotide sequencing that the genomic sequences of prototypic
      alleles from all three lineages diverge significantly and that lineage 3 is
      derived from lineage 2 by two insertional events in intron 2. One insert,
      composed of a member of B1 short interspersed repetitive elements (SINEs), occurs
      508 base pairs (bp) 3' of exon 2, and the other, 1141 bp 3' of exon 2 within the
      retroposon that distinguishes lineage 2 from lineage 1. To assess the
      evolutionary stability of these lineages and the extent of ancestral
      polymorphisms of Ab within Mus species, we extended our restriction site
      polymorphism analysis to include 86 alleles from 120 independently derived H2
      haplotypes from 12 separate species and subspecies of Mus. A phylogenetic tree
      revealing the relationships of these Ab alleles with respect to restriction site
      polymorphisms, but excluding the retroposon insertions, demonstrated that these
      lineages have distinctive genomic structures beyond the retroposon polymorphisms.
      In summary, these mouse Ab genes were produced from successive retroposon
      insertion events. Lineage 1 and 2 were detected in a variety of Mus species,
      including Mus caroli, indicating that these lineages diverged more than 2 million
      years ago. Lineage 3 alleles were found only in the Mus musculus subspecies,
      suggesting that it diverged from lineage 2 more recently. These results indicate
      that all three lineages of Ab have persisted through several speciation events in
      the genus Mus.

PMID- 8550096
TI  - Characterization of Mhc genes in a multigenerational family of ring-necked
      pheasants.
AB  - Little is known about the major histocompatibility (Mhc) genes of birds in
      different taxonomic groups or about how Mhc genes may be organized in avian
      species divergent by evolution or habitat. Yet it seems likely that much might be
      learned from birds about the evolution, organization, and function of this
      intricate complex of polymorphic genes. In this study a close relative of the
      chicken, the ring-necked pheasant (Phasianus colchicus), was examined for the
      presence and organization of Mhc B-G genes. The patterns of restriction fragments
      revealed by chicken B-G probes in Southern hybridizations and the patterns of
      pheasant erythrocyte polypeptides revealed in immunoblots by antisera raised
      against chicken B-G polypeptides provide genetic, molecular, and biochemical data
      confirming earlier serological evidence for the presence of B-G genes in the
      pheasant, and hence, the presence of a family of B-G genes in at least a second
      species of birds. The high polymorphism exhibited by the pheasant B-G gene family
      allowed genetic differences among individuals within the small experimental
      population in this study to be detected easily by restriction fragment patterns.
      Further evidence was found for the organization of the pheasant Mhc class I and
      class II genes into genetically independent clusters. Whether these gene clusters
      are fully comparable to the B and Rfp-Y systems in the chicken or whether yet
      another organization of Mhc genes has been encountered in the pheasant remains to
      be determined.

PMID- 8550097
TI  - An approach to mapping haplotype-specific recombination sites in human MHC class
      III.
AB  - Studies of the major histocompatibility complex (MHC) in mouse indicate that the
      recombination sites are not randomly distributed and their occurrence is
      haplotype-dependent. No data concerning haplotype-specific recombination sites in
      human are available due to the low number of informative families. To investigate
      haplotype-specific recombination sites in human MHC, we here describe an approach
      based on identification of recombinant haplotypes derived from one conserved
      haplotype at the population level. The recombination sites were mapped by
      comparing polymorphic markers between the recombinant and assumed original
      haplotypes. We tested this approach on the extended haplotype HLA A3; B47; Bf*F;
      C4A*1; C4B*Q0; DR7, which is most suitable for this analysis. First, it carries a
      number of rare markers, and second, the haplotype, albeit rare in the general
      population, is frequent in patients with 21-hydroxylase (21OH) defect. We
      observed recombinants derived from this haplotype in patients with 21OH defect.
      All these haplotypes had the centromeric part (from Bf to DR) identical to the
      original haplotype, but they differed in HLA A and B. We therefore assumed that
      they underwent recombinations in the segment that separates the Bf and HLA B
      genes. Polymorphic markers indicated that all break points mapped to two segments
      near the TNF locus. This approach makes possible the mapping of preferential
      recombination sites in different haplotypes.

PMID- 8550098
TI  - Rapid cloning of any rearranged mouse immunoglobulin variable genes.
AB  - Immunoglobulins (Ig) have been the focus of extensive study for several decades
      and have become an important research area for immunologists and molecular
      biologists. The use of polymerase chain reaction (PCR) technology has accelerated
      the cloning, sequencing, and characterization of genes of the immune system.
      However, cloning and sequencing the Ig variable (V) genes using the PCR
      technology has been a challenging task, primarily due to the very diverse nature
      of Ig V region genes. We have developed a simple, rapid, and reproducible PCR
      based technique to clone any rearranged mouse Ig heavy or light chain genes. A
      close examination of all Ig heavy and light chain V gene families has resulted in
      the design of 5' and 3' universal primers from regions that are highly conserved
      across all heavy or light chain V gene families, and the joining or constant
      regions, respectively. We present our strategy for designing universal primers
      for Ig V gene families. These primers were able to rapidly amplify the rearranged
      Ig V genes, belonging to diverse Ig V gene families from very different cell
      lines, i.e., J558, MOPC-21, 36-60, and a chicken ovalbumin specific B-cell
      hybridoma. In addition, the present study provides the complete alignment of
      nucleotide sequences of all heavy and light chain variable gene families. This
      powerful method of cloning Ig V genes, therefore, allows rapid and precise
      analysis of B-cell hybridomas, B-cell repertoire, and B-cell ontogeny.

PMID- 8550099
TI  - Mouse HLA-DPA homologue H2-Pa: a pseudogene that maps between H2-Pb and H2-Oa.

PMID- 8550100
TI  - cDNA sequence of cattle MHC class I genes transcribed in serologically defined
      haplotypes A18 and A31.

PMID- 8550101
TI  - The nucleotide sequence of HLA-B*2704 reveals a new amino acid substitution in
      exon 4 which is also present in HLA-B*2706.

PMID- 8550102
TI  - Na+/H+ exchanger-1 alleles: strain distribution and correlation with activity.

PMID- 8550103
TI  - Conservation of Tcrg-V5 and limited allelic sequence polymorphism of the other
      Tcrg-V genes used by mouse tissue-specific gd-T lymphocytes.

PMID- 8550104
TI  - PCR cloning and sequencing of a CD3-specific monoclonal antibody.

PMID- 8550105
TI  - Identification of the new HLA-DRB1*0812 allele detected by sequencing based
      typing.

PMID- 8550106
TI  - Characterization of a new HLA-B allele (B*3702) generated by an intronic
      recombination event.

PMID- 8550107
TI  - Nucleotide sequence of the ACI rat CTLA-4 molecule.

PMID- 8550108
TI  - Elie Metchnikoff (1845-1916)

PMID- 8550109
TI  - Oxygen toxicity and antioxidants: state of the art.
AB  - Although the use of oxygen as metabolic fuel allows an attractive harvest of
      energy rich phosphates per molecule of glucose, a significant fraction of oxygen
      utilized by the body incompletely reduced and is known to be toxic. Such
      partially reduced forms of oxygen and some of their derivatives are highly
      reactive pro-oxidants that are collectively referred to as reactive oxygen
      species (ROS). A multitude of factors are known to modulate the amount of ROS
      formation in the body. To escape ROS dependent toxicity biological structures
      have their protective machinery in the form of physiological antioxidants. It
      appears that the physiological antioxidants are not independently capable of
      completely detoxifying the ROS constantly produced by the body. The supply of
      exogenous antioxidants is thus crucial. Endo- and exogenous antioxidants act in
      concert to minimize ROS dependent damage. ROS are involved in the pathogenesis of
      a large number of clinical disorders. The sensitive balance between the pro- and
      anti- oxidant forces in the body appears to be very crucial in determining the
      state of health, well being and longevity. This article presents an introductory
      overview covering the current concepts related to oxidants and antioxidants with
      special reference to human health.

PMID- 8550110
TI  - Growth factors in pregnancy.
AB  - The role of growth factors in pregnancy is a rapidly expanding subject. With the
      advent of molecular biological techniques more and more detailed information is
      available to the researcher. This review does not attempt to be exhaustive in its
      coverage of growth factors in pregnancy, rather it tries to give a brief taste of
      the possible roles that they may play in pregnancy by considering three specific
      factors, leukaemia inhibitory factor, colony stimulating factor-1 and vascular
      endothelial growth factor.

PMID- 8550111
TI  - Renin-like activity in the rat epididymis.
AB  - 'Whole' cauda epididymal homogenate and individual components of the cauda
      epididymis viz, cauda epididymal cells, epididymal plasma and sperm cells, as
      well as the blood plasma of the rat were screened for renin-like activity by in
      vivo method. Enzyme activity was high in 'whole' cauda epididymal homogenate, but
      very low in blood plasma. Evaluation of individual components of the epididymis
      revealed a relatively high enzyme activity in the epididymal cells but low
      activity in epididymal plasma and epididymal sperm cells. The high activity in
      epididymal cells was not affected by efferent duct ligation for 8 weeks and
      bilateral nephrectomy. Like most other epididymal functions, renin-like activity
      in the epididymis was androgen dependent. It was concluded that cauda epididymis
      of the rat contains the enzyme renin, whose activities may be predominantly
      intracellular.

PMID- 8550112
TI  - Co-localization of c-fos protein and protein kinase C gamma in the rat brain
      following anodal polarization.
AB  - The expression of protein kinase c gamma (PKC gamma) and c-fos protein was
      examined by means of double labeling in the rat brain in relation to the
      molecular mechanism of central plastic changes associated with anodal
      polarization. Under normal, non-polarized condition, approximately 75% of all fos
      positive neurons in the neocortex were immunopositive for PKC gamma. Conversely,
      nearly all PKC gamma positive neurons were fos immunopositive. Although both
      pyramidal and non-pyramidal neurons express both types of protein, the pyramidal
      cell type represents the vast majority. An anodal direct current of 3.0 microA
      for 30 min to the surface of the left sensorimotor cortex resulted in a
      pronounced increase in the intensity of immunoreactivity for both PKC gamma and c
      fos protein ipsilateral to the polarization. Approximately, 91% of fos positive
      neurons in the polarized neocortex was also intensely immunoreactive for PKY
      gamma. The high degree of codistribution of both transduction proteins in
      specific neurons following anodal polarization suggests the functional connection
      between PKY gamma activation and c-fos expression in polarization phenomenon.

PMID- 8550113
TI  - Effect of acute haemodilution on right atrial type-B receptor activity in
      anaesthetized cats.
AB  - In order to investigate whether the sensitivity of atrial type-B receptors to its
      natural stimulus is altered during acute haemodilution, experiments were
      conducted in nine anaesthetized, artificially ventilated and thoracotomized cats.
      Haemodilution was achieved by replacement of blood by the same volume of dextran
      (MW 150000). Atrial receptor activity, arterial blood pressure, right atrial
      pressure and ECG were recorded. Heart rate was calculated from ECG records.
      Arterial blood hematocrit was measured. Mean arterial blood pressure and heart
      rate were not altered by haemodilution even at a hematocrit level of 12.17 +/-
      0.93 percent. Average activity of type-B atrial receptors, mean right atrial
      pressure, right atrial peak 'v' pressure, right atrial initial 'v' pressure and
      right atrial 'v' wave amplitude were changed significantly (r < 0.05) during
      acute haemodilution when the hematocrit was 12.17 +/- 0.93 percent but the atrial
      type-B receptor activity per cycle did not show any significant change. Average
      activity of type-B receptors increased from 8.56 +/- 1.02 spikes/sec to 9.56 +/-
      1.11 spikes/sec. Mean right atrial pressure, right atrial 'v' wave amplitude,
      right atrial peak 'v' pressure increased significantly (P < 0.05) from respective
      control values. Right atrial initial 'v' wave pressure decreased significantly.
      Heart rate changed from 168.11 +/- 5.42 beats/min to 170.89 +/- 5.65 beats/min.
      Mean arterial pressure changed from 134.33 +/- 0.89 mmHg to 135.67 +/- 1.46
      mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8550114
TI  - Effects of sex steroids on the concentrations of some brain neurotransmitters in
      male and female rats: some new observations.
AB  - Concentrations of some neurotransmitters, viz. noradrenaline (NA), 5
      hydroxytryptamine (5-HT), dopamine (DA), histamine (H) and gamma aminobutyric
      acid (GABA) in a part of brain consisting of medulla, pons, mid brain, thalamus
      and hypothalamus were measured in ovariectomized (OVx), intact (+Te) and
      castrated male (Tex) rats both without injecting estrogen (E) or E and
      progesterone (P) as well as after E and E+P administration. Some effects, (which,
      as far as we are aware of) have not been previously reported, were noted (in
      addition to other already documented observations). These include: (i) castration
      in males causes a fall of the level of GABA, NA, 5-HT and DA, (ii) E therapy also
      causes fall of the levels of GABA, NA and 5-HT and thus E therapy produces
      similar results like those of bilateral orchidectomy, (iii) P therapy not only
      reverses the fall of (GABA) but raises it more than the normal value, (iv) P
      therapy, it appears (although faintly), retrieve to some extent the fall of NA
      level due to E therapy, (v) Like the OVx rats, castrated as well as intact rats
      also showed a fall in the 5-HT level with E treatment but showed a rise when
      treated by E followed by P, (vi) In between the castrated males and castrated
      females, the concentrations of all these brain neurotransmitters differ. The
      probable significances have been discussed.

PMID- 8550115
TI  - Cyclodiene insecticides-induced changes in the central depressive effect of
      chlorpromazine in rats.
AB  - Spontaneous motor activity (SMA), conditioned avoidance response (CAR), muscle
      coordination (MC) and pentobarbital sleep were tested in rats treated orally for
      90 days with tolerated doses of the cyclodiene insecticides, aldrin (1 mg/kg) and
      endosulfan (2 mg/kg). The same tests were repeated in similarly treated animals
      after injecting chlorpromazine (4 mg/kg, i.p.). Both the insecticides shortened
      pentobarbital sleeping time indicating their microsomal enzyme inducing property.
      Aldrin suppressed SMA, CAR and MC, whereas endosulfan stimulated SMA, inhibited
      CAR and unaltered MC. However, their concurrent action with CPZ did not result in
      change in the central depressive effects of the latter, but its potency during
      the course of its action was altered. Its potency 15 min after injection was
      greater and 60-180 min later was lesser in these animals than that observed in
      control animals. This finding was interpreted to suggest that aldrin and
      endosulfan has quickened the biotransformation of CPZ and thereby shortened its
      duration of action. A temporary promotion of its potency was accounted to its
      active metabolites, since prior to inactivation, CPZ is known to be metabolized
      by the microsomal enzymes to active compounds.

PMID- 8550116
TI  - Comparative effects of atenolol versus nifedipine on serum lipids and other
      biochemical parameters in diabetic and non-diabetic hypertensive subjects.
AB  - A controlled clinical trial on 65 patients was performed to compare the effects
      of nifedipine and atenolol in diabetic and non-diabetic hypertensive patients.
      Patients were from 45 to 70 years in age. The diabetic hypertensive patients and
      non-diabetic essential hypertensive patients randomly received atenolol (50-100
      mg per day) or nifedipine (10-20 mg per day) for 9 months. Both the drugs
      effectively controlled the blood pressure throughout the therapy. Atenolol
      treatment significantly increased triglyceride levels and decreased the HDL
      cholesterol levels after 9 months in both groups. However, nifedipine therapy did
      not alter lipid levels to any significant extent. Both drugs did not alter blood
      glucose, serum creatinine and blood urea levels. It may be concluded from the
      present study that nifedipine is preferable to atenolol as it does not alter
      lipid profile to any significant extent in diabetic and non-diabetic hypertensive
      patients.

PMID- 8550117
TI  - Studies on psychomotor performance in healthy volunteers after diazepam,
      propranolol and alcohol given alone or in combination.
AB  - The effects of diazepam, propranolol or alcohol alone or in combination with each
      other were examined in ten normal healthy volunteers on tests of psychomotor
      function. Results showed impaired psychomotor performance persisting upto 4-5 h
      when the aforementioned agents given singly were tested on simple reaction time
      (SRT), multiple choice reaction time (MCRT) and critical flicker fusion frequency
      (CFFF) tasks. Digit cancellation task (DCT) was similarly affected by diazepam
      and alcohol only. No summation of adverse effects on psychomotor performance was
      noted when a combination of diazepam and alcohol, diazepam-propranol or alcohol
      plus propranolol were tested on SRT and MCRT. An additive impairment of CFFF was
      observed with alcohol - propranolol combination only. No summation of
      pharmacodynamic effects on DCT were noted when different combinations were used.

PMID- 8550118
TI  - A comparative study of prescribing pattern at different levels of health care
      delivery system in Bangalore district.
AB  - A study of prescribing pattern in tertiary, primary and urban general practice
      levels of the Indian health care delivery system was undertaken by analyzing 1810
      prescriptions for 3932 drugs. The study evaluated feasibility of data acquisition
      methods and compared the prescribing frequency of various drug groups and of
      individual drugs in three commonly used categories. The mean number of drugs per
      prescription was highest in urban general practice (2.41). The four most
      frequently prescribed drug groups were antibacterials, vitamins, nonsteroidal
      antiinflammatory drugs (NSAIDs) and respiratory drugs. The study delineates the
      differences in prescribing frequency of drug groups and individual drugs across
      the three levels of health care and the results suggest intervention strategies
      to promote rational drug therapy.

PMID- 8550119
TI  - Administration of the plasticizer di (2-ethylhexyl) phthalate alters
      glycoconjugate profile.
AB  - This study was undertaken to evaluate the level of glycoproteins and sialic acid
      in rats fed di (2-ethylhexyl)-phthalate (DEHP) in the diet for 24 weeks. Protein
      bound hexose, hexosamine and sialic acid were increased in plasma and liver of
      rats treated with DEHP, whereas the erythrocyte membrane showed a reduction
      following DEHP administration. Evaluation of glycoproteins is a useful indicator
      of the carcinogenic process. It is suggested that profound alterations in
      membrane components observed in the present study may be related to the
      carcinogenic potential of DEHP.

PMID- 8550120
TI  - Comparison of pulmonary function amongst Ladakhi, Delhi, Vanvasi and Siddi boy
      athletes.
AB  - Lung functions were studied in contemporary healthy boy athletes of Ladakhi,
      Delhi, Vanvasi and Siddi origin. As lung function are related to ethnic and
      environmental factors, the aim of the study was to compare the lung function in
      boys belonging to these four groups. Vital Capacity (VC), Forced Vital Capacity
      (FVC), Forced Expiratory Volume in 1st second (FEV1), Expiratory Reserve Volume
      (ERV) and Inspiratory Capacity (IC) were recorded using conventional closed
      circuit spirometry. Maximum Voluntary Ventilation (MVV) was estimated collecting
      expired air during deep and rapid breathing in a 100 litres meterological balloon
      for a period of 15 seconds and measuring its volume. It was found that Ladakhi
      boys were having significantly higher VC, FVC and FEV1 values than their
      counterparts. However, there was no significant difference in MVV amongst
      Ladakhi, Delhi, Vanvasi and Siddi boys. Our results suggest that size of the lung
      is governed by genetic, environmental and nutritional factors and confirm that
      physical training during growth may help in developing a greater endurance in
      respiratory muscles.

PMID- 8550121
TI  - Role of hyperphagia in structural changes of small intestine during lactation.
AB  - The present study was conducted to investigate the cause of the structural
      changes of small intestine during lactation in albino rats. Anatomical
      measurements (total length, total wet weight and total dry weight) and
      histological studies of small intestine were undertaken in virgin control rats,
      lactating control rats, lactating rats with restricted food intake and lactating
      rats with restricted litter size. Restriction of food intake prevented the growth
      of small intestine during lactation, while restriction of litter size had no
      effect. Results indicate that the structural changes in small intestine are due
      to work hypertrophy secondary to hyperphagia and not due to any hormonal factors.

PMID- 8550122
TI  - Vitamin E protects intestinal basolateral membrane from CMF-induced damages in
      rat.
AB  - CMF is a combination of anticancer chemotherapeutic agents Cyclophosphamide,
      Methotrexate and 5-Fluorouracil. Vitamin E protects the basolateral membrane
      (BSM) from CMF induced lipid peroxidative damages. Rats were treated
      intravenously with cyclophosphamide-10 mg, methotrexate-1.0 mg and 5-fluorouracil
      10 mg per kg body weight for six cycles. Vitamin E (600 mg/kg body weight) was
      administered orally, daily. Intestinal basolateral membrane bound ATPases
      (3.6.1.3), Alkalinephosphatase (3.1.1) and 5'-Nucleotidase (3.1.3.5) were
      protected by co-administration of vitamin E with CMF. In CMF treated rats the
      lipid peroxidation levels were found to be elevated with a significant depletion
      in membrane sulfhydryl groups. In vitamin E co-administered animals, the enzyme
      activities were found to be restored with concomitant reduction in
      malondialdehyde levels and an increase in the sulfhydryl groups. The membrane
      cholesterol and phospholipid levels which were altered in CMF treated rats were
      bought back to the normal in co-administration of vitamin E.

PMID- 8550123
TI  - Pharmacodynamic effects of pilocarpine eye drop enhanced by decreasing its volume
      of instillation.
AB  - Previous studies have proved that as the volume of the drug solution instilled
      into the eye is decreased, the fraction of the dose absorbed into the ocular
      tissue is increased and the adverse drug reactions lowered. The present study
      investigated the acute effects of different drop volumes (10 microliters, 20
      microliters, 40 microliters, and 80 microliters) of pilocarpine nitrate (2%) on
      pupil diameter, heart rate, and adverse reaction profile, in 12 healthy human
      volunteers. The drop volumes of 10 microliters and 20 microliters produced more
      miosis and less side effects than 40 microliters and 80 microliters drop volumes.
      This may be due to more penetration of the drug into the ocular tissue and less
      drainage into the nasolacrimal system.

PMID- 8550124
TI  - Alloxan diabetes in Swiss mice: activity of Na(+)-K(+)-ATPase and succinic
      dehydrogenase.
AB  - The activities of two enzymes viz: Na(+)-K(+)-ATPase and succinic dehydrogenase
      (SDH) in brain and liver of alloxan diabetic Swiss albino mice are reported.
      Alloxan diabetes caused significant decrease in the activity of Na(+)-K(+)-ATPase
      reflecting reduced glucose transport across the cell membrane. On the contrary,
      the observed enhanced activity of the enzyme SDH is attributed to increased
      supply of TCA cycle substrates from accelerated oxidation of fatty acids.

PMID- 8550125
TI  - Protection of CCL4-induced liver damage in rats by some calcium channel blockers.
AB  - Liver necrosis was produced in rats by administering 3 doses o a mixture o carbon
      tetrachloide+olive oil, 2 ml/kg, ip. The liver damage was evidenced by the
      elevated levels serun aspartate aminotrans ferase (AST), alanine aminotransferase
      (AIT) and gamma glutamyl transpeptidase (gamma-GT) and by histopathological
      observations of liver sections. Nitrendipine, nimodipine and nisoldipine (1
      mg/100 g of rat, ip) significantly reduced these elevated levels of AST, AIT and
      gamma-GT. Carbon tetrachloride induced liver necrosis was also found to be
      significantly reduced in nitrendipine, nimodipine and nisoldipine pre-treated
      animals as observed macroscopically and histologically.

PMID- 8550126
TI  - Effect of amitriptyline on blood glucose level in rabbits.
AB  - Effect of single graded doses of amitriptyline (4, 8 and 16, mg/kg, p.o.) were
      observed on blood glucose level in 18 h fasted albino rabbits. All the doses of
      Amitriptyline produced significant hyperglycemia at 4 h, which attained a peak at
      24 h with 16 mg/kg dose and appears to be due to blockade of the uptake of
      monominergic transmitters across the axoplasmic membrane, It (16 mg/kg) also
      produced glucose intolerance during early hours probably due to interference with
      gastrin function.

PMID- 8550127
TI  - The isolated air perfused rat heart.
AB  - A simple method has been developed for continuous monitoring of metabolic
      activity of an isolated, perfused rat heart by O2/CO2 respirometer. Since
      respirometer provides vital data on oxygen consumption and carbon dioxide
      production of a preserved organ on a continuous basis over a long period of time,
      it will be possible to use this method to monitor viability of not only isolated
      heart but also any given donor organ under preservation.

PMID- 8550128
TI  - Serum lipid profile in children of coronary heart disease patients.
AB  - Serum lipid and lipoprotein cholesterol levels were analysed in 44 children from
      5-14 years of age (index), belonging to 29 parents diagnosed as coronary artery
      disease (CAD). 314 children of parents without any CAD served as control. Index
      group had significantly (P < .05) higher levels of total cholesterol (Tch),
      triglycerides (TG) and very low density lipo-proteins cholesterol (VLDLc) and low
      levels of high density lipoprotein cholesterol (HDLc) (P < .05). Index group
      revealed higher levels of cholesterol, triglycerides and low density lipoprotein
      cholesterol in 31.8%, 6.8% and 36% cases respectively. HDLc did not show any
      significant variation. Index group whose parents had hypercholesteremia (Tch >
      260 mg/dl) with CAD had raised levels of Tch, TG, LDLs and VLDLc when compared
      with control group (P < .05).

PMID- 8550129
TI  - Effect of thyroxine on experimental bronchospasm in guinea pigs.
AB  - Effect of Thyroxine was studied in histamine induced bronchospasm in guinea pigs.
      Chronic treatment with the drug significantly protected against experimental
      bronchospasm. Thyroxine also potentiated salbutamol evoked bronchodilation in
      this experimental model. Up-regulation of beta-2 adrenoceptors in bronchial
      smooth muscle may be the probable mechanism of action of thyroxine.

PMID- 8550130
TI  - Effects of nitroxazepine on diastolic blood pressure in mild hypertensive
      patients--a short term clinical study.
AB  - In a double blind short term clinical study, nitroxazepine has been found to be
      superior over placebo in reducing the diastolic blood pressure in mild
      hypertensive patients. In short term open clinical trial design nitroxazepine (25
      mg PO, HS) has been found to be superior and better tolerated than diazepam (5 mg
      PO, HS). In open clinical trial design, nitroxazepine (25 mg PO, HS) reduced the
      diastolic blood pressure to the target level (100 mm Hg and less) effectively
      controlling the uncontrolled hypertensive patients receiving maintenance dose of
      beta blockers. There was no such beneficial effect in patients receiving
      maintenance doses of other antihypertensive drugs (pilot study). Adverse drug
      reactions like disturbed sleep in one, uneasiness in 3, palpitation in one and
      dryness of mouth in one patient have been observed.

PMID- 8550131
TI  - Effect of angiotensin converting enzyme inhibitor (captopril) on gastric ulcer
      production in pylorus ligated rats.
AB  - Intraperitoneal injection of Angiotensin Converting Enzyme inhibitor, captopril,
      reduced significantly (P < 0.001), the production of gastric ulcers in pylorus
      ligated albino rats, compared to the control groups, irrespective of the dose
      schedule--single or quadruple. In the light of evidence available in the
      literature, it is reasonable to hypothesise that the anti-ulcer effect of
      captopril may be mediated through prostaglandins.

PMID- 8550132
TI  - Effect of application of gamma amino butyric acid at the medial preoptic area on
      sleep-wakefulness.
AB  - Intracerebral microinjections of gamma amino butyric acid were given bilaterally
      at the medial preoptic area (mPOA) to determine the possible role of this
      neurotransmitter in the genesis and regulation of sleep-wakefulness. GABA (50
      micrograms/0.2 microliters) when administered through chronically implanted
      cannulae in free moving rats, did not produce any significant alterations in
      sleep-wakefulness. This may be attributed either to the non-involvement of GABA
      at the level of mPOA in the regulation of sleep, or to other factors like the low
      dose and rapid breakdown of the injected drug.

PMID- 8550133
TI  - Pharmacokinetics of antipyrine and theophylline: unaltered by multi-dose
      omeprazole treatment in rabbits.

PMID- 8550134
TI  - Hepatic functions in epileptics on sodium valproate monotherapy.

PMID- 8550135
TI  - Metronidazole extravasation causing digital gangrene.

PMID- 8550136
TI  - Clinical course in 52 severely wounded patients treated in the intensive care
      unit during the war in Croatia.
AB  - Fifty-two severely wounded patients, admitted directly from a battlefield or
      after surgical treatment in a war hospital, were treated in the Surgical
      Intensive Care Unit of the 'Sisters of Mercy' University Hospital in Zagreb
      during the 1991 war in Croatia. Considering the severity of the wounds, blood
      loss was not as severe as expected. This can be attributed to the nature of the
      injuries as most of the patients were wounded by fragments of explosive devices
      which cause less tissue destruction than military bullets. Low serum potassium
      levels, metabolic acidosis, low total protein levels and consequently low serum
      calcium levels correlated with wound severity. Low serum potassium levels were
      caused by its redistribution. Reperfusion liver injury was also present.
      Consumption coagulopathy was one of the characteristic disturbances in this type
      of injury. There was a relatively big difference between fluid input and output
      caused by fluid loss through drain sites and large open wound surfaces. The low
      mortality of the severely wounded was due to their young age and the well
      organized military medical service which was developed from the civilian medical
      service in a short time.

PMID- 8550137
TI  - Vascular trauma of the upper limb and associated nerve injuries.
AB  - In an analysis of vascular audit data on upper limb vascular trauma over a 10
      year period in a major UK injury centre it was found that 15 patients required
      operation for subclavian or axillary artery injuries. Eleven cases were the
      result of blunt injury. Twelve patients had an ischaemic arm on presentation, all
      of whom had an associated brachial plexus lesion. Subclavian or axillary artery
      transections, irrespective of limb viability, also were found to have associated
      plexus trauma. Twenty-eight patients had brachial artery injuries repaired, 46
      per cent of whom had an associated nerve injury. A good functional result was
      achieved in only half of the patients who underwent repair of a peripheral nerve
      injured in association with the brachial artery. Vascular reconstruction was
      successful in all cases. The long-term outcome of brachial plexus lesions was
      very poor and the role of exploratory surgery is discussed. The long-term outcome
      of upper limb injury is not dependent on the vascular injury which can be
      successfully managed, but upon the recognition, treatment, and outcome of the
      associated nerve injuries.

PMID- 8550138
TI  - The functional prognosis of thoracolumbar vertebrae fractures without
      neurological deficit: a long-term follow-up study of British Army personnel.
AB  - Seventy-three British Army personnel were followed up for a mean of 64 (range 6
      120) months after sustaining a thoracolumbar vertebral fracture without
      neurological deficit. Road-traffic accidents were the commonest cause of injury.
      An excellent functional outcome was achieved in 74 per cent of cases, good in 15
      per cent, fair in 10 per cent and poor in 1 per cent. The functional outcome was
      not significantly affected by the fracture type, severity, region or treatment
      received. This study has important medico-legal implications.

PMID- 8550139
TI  - Protein immunohistochemistry as a means of unravelling the mysteries of fracture
      repair.
AB  - The repair of a closed fracture of the adult tibial diaphysis was studied by an
      immunohistochemical technique which localized bone sialoprotein in situ.
      Immunoreactivity was observed in newly formed bone trabeculae, in the periosteum
      and endosteum and in the callus cartilage.

PMID- 8550140
TI  - Late open nailing for neglected femoral shaft fractures.
AB  - The results of open nailing in 14 cases of neglected closed femoral shaft
      fractures were reviewed. The mean patient's age was 28 years (range, 17-50). The
      mean delay to definitive treatment was 4.6 months (range 2-10). All fractures
      were malaligned with an average shortening of 4.9 cm (range 2.5-6.5). All cases
      underwent one-stage open nailing using the Kuntscher nail fixation. The femur was
      shortened at the fractured end of one or both fragments to accomplish reduction
      in nine cases. The mean length of the bone resected was 9 mm (range 5-15). Only
      local callus was used for bone grafting in all cases. There were no neurovascular
      complications. All fractures healed an average of 3 months (range 2-4) after
      operation. Six cases had regained full knee flexion at the time of the latest
      follow up. Eight cases had decreased knee flexion with an average arc of knee
      flexion of 119 degrees (range, 100-125). The mean length of hospital stay was 7
      days (range, 5-12). The method was found to be safe and effective with acceptable
      shortening and knee motion.

PMID- 8550141
TI  - Multiple guide wire technique for removal of the short distal fragment of a
      fractured intramedullary nail.
AB  - A method of removing a short distal fragment of a fractured intramedullary nail,
      using impacted olive-tipped guide wires, is described. We have used this
      technique with success when there has been a very short segment of nail left
      distally. This method gives improved grip and control of alignment of the nail
      fragment during extraction.

PMID- 8550142
TI  - Children's head injuries in the Vietnamese refugee population in Hong Kong.
AB  - All Vietnamese patients with head injuries from two of the largest refugee camps
      in Hong Kong are routinely referred to the Neurosurgical Unit of the Prince of
      Wales Hospital for management. In order to determine the epidemiology of head
      injuries in this population group, we have retrospectively reviewed all
      hospitalized cases over a 4 year period from January 1990 to December 1993. We
      have found a unique social situation in this population group, with an unusually
      high proportion of paediatric cases (2253 per 100,000 children aged 5 years or
      less), compared with other epidemiological studies. The most common mechanism of
      injury in between 57 and 75 per cent of cases was a fall from bed. Based on this
      information, appropriate preventive measures have been recommended and have
      successfully decreased the incidence of head injuries. This study demonstrates
      the value and effectiveness of epidemiological studies in identifying a
      previously unrecognized health risk in a specified population group.

PMID- 8550143
TI  - A study of metatarsal fractures in children.
AB  - The purpose of our study was to document the sites and distribution of mid-foot
      and fore-foot fractures in children, relating them to the pattern of injury with
      particular reference to the first metatarsal. The clinical records and
      radiographs of 388 children with foot injuries were examined. A total of 62
      metatarsal and seven tarsal fractures were identified in 60 children. The
      commonest fracture was of the fifth metatarsal, 45 per cent overall; 90 per cent
      of these children were over 10 years old. In children under 5 years old, first
      metatarsal fractures accounted for 73 per cent, but in children over 5 years old,
      these fractures accounted for only 12 per cent of the total. In all, 6.5 per cent
      of all fractures and 20 per cent of first metatarsal fractures went unrecognized
      at the initial attendance.

PMID- 8550144
TI  - Severe snowboarding injuries.
AB  - Thirty-seven consecutive patients with severe snowboard-related injuries (defined
      by referral to a Level I trauma centre) were reviewed. The type and mechanism of
      each injury were examined and found to be similar to those reported for skiers.
      Mild closed head injuries were common (54 per cent). Head and abdominal injuries
      were more common among snowboarders than skiers, but chest and skeletal injuries
      were rare. There were no deaths. Serious snowboarding injury rates were similar
      to those for serious skiing injuries. The incidence of snowboarding injuries
      sufficiently severe to require tertiary referral was estimated at 0.03
      injuries/1000 snowboarder days. Similar to reports of minor snowboarding injury,
      these data indicate that injury patterns in more serious snowboarding accidents
      are quite different from those of serious downhill skiing accidents. Injured
      snowboarders suffer splenic injuries more often and chest and spinal injuries
      less often than do skiers, and should be evaluated for blunt injuries with these
      statistical differences in mind.

PMID- 8550145
TI  - Severe motorcycle injury in Mersey region and North Wales.
AB  - Ninety-three patients were involved in serious motorcycle accidents (death or
      Injury Severity Score more than 15) during a 1-year period among a total of 554
      victims of serious road traffic accidents studied at 16 district general and
      teaching hospitals. There were 91 males and two females. The average age was 29
      years (range 15-81 years). Of these, 32 per cent died at the scene of the
      accident or in transit; 68 per cent arrived alive at the above hospitals. Of the
      latter, 30 per cent died in hospital. The commonest cause of death was multiple
      injuries. The Injury Severity Score of patients admitted to hospital was a mean
      of 32.1. The Glasgow Coma Score was below 9 in 33.8 per cent. Of those admitted
      to hospital, the average length of stay was 38.7 days. 67 per cent were admitted
      to intensive therapy unit of whom 41.3 per cent had to be ventilated for an
      average of 3.55 days. There were four preventable deaths among the patients who
      died after being admitted to hospital. Many body areas are frequently injured in
      motorcycle accidents which occur usually in fit males. Careful assessment along
      with vigorous and aggressive treatment is particularly important for this group.
      Access to a specialized trauma centre would be beneficial.

PMID- 8550147
TI  - An unusual case of isolated flexor digitorum profundus laceration.

PMID- 8550146
TI  - Blunt liver injury: 3 hour and 35 minute occlusion of the hepatoduodenal
      ligament.

PMID- 8550148
TI  - Pseudo-aneurysm of the lateral circumflex humeral artery following external
      fixation of a free fibular transfer.

PMID- 8550149
TI  - Endoscopic intrapancreatic stent for traumatic duct injury.

PMID- 8550150
TI  - Stroke following neck injury in a rugby player.

PMID- 8550151
TI  - A case of pulmonary tuberculosis arising at the site of injury.

PMID- 8550152
TI  - Refracture of a healed tibial shaft fracture after irradiation for post-traumatic
      squamous-cell carcinoma.
AB  - A 58-year-old man, who had been operated on 17 years ago for an open Grade III
      tibial shaft fracture, developed 14 years after the fracture had healed a poorly
      differentiated squamous cell carcinoma at the site of the old scar. Seventeen
      years after the original injury, the carcinoma was completely excised and the
      area irradiated. Fourteen months later a spontaneous fracture of the tibial shaft
      occurred at the same site. After radical excision of the necrotic bone and
      affected skin, AO-external osteosynthesis was performed which failed, and 8
      months after surgery a septic pseudarthrosis occurred which persisted, though no
      local recurrence of the carcinoma was clinically or histologically diagnosed.
      Amputation in the upper third of the tibia was successful without local or
      systematic recurrence during follow-up.

PMID- 8550153
TI  - Bilateral fibula head fractures complicating an epileptic seizure.

PMID- 8550154
TI  - Unrecognized fracture through the base of superior articular facet of cervical
      spine presenting with transient tetraparesis.

PMID- 8550155
TI  - Cough fracture of the first rib.

PMID- 8550156
TI  - The use of the Goodall Targetting Device for application of external fixators in
      the treatment of pilon fractures.

PMID- 8550157
TI  - Irreducible syndesmosis due to an entrapped posterior fragment.

PMID- 8550158
TI  - A new drill guide to simplify coraco-clavicular screw fixation.

PMID- 8550159
TI  - The perceived relationship between neck symptoms and precedent injury.

PMID- 8550160
TI  - Complex dislocation of the metacarpophalangeal joint of the index finger with
      sesamoid entrapment.

PMID- 8550161
TI  - Recurrent ipsilateral fracture of the penis.

PMID- 8550162
TI  - Pre-hospital management of patients with severe thoracic injury.
AB  - The physiological variables of oxygen saturation, blood pressure and pulse rate
      were compared in the pre-hospital phase and on arrival at hospital in a group of
      63 patients with severe chest injury. Eighty-nine pre-hospital thoracic drainage
      procedures were carried out. Pre-hospital Advanced Trauma Life Support (ATLS) was
      associated with a significant improvement in all three variables. Median oxygen
      saturation increased by 17 per cent (P < 0.001), median blood pressure increased
      from 90 to 120 mmHg (P < 0.001) and median pulse rate decreased from 125 to 105
      (P < 0.001). Pre-hospital intervention is indicated for tension pneumothorax, and
      contraindicated for haemothorax without respiratory compromise. In other
      situations further evidence is required, and standard ATLS protocols should be
      used until this is available.

PMID- 8550163
TI  - A new functional brace for the treatment of Colles' fractures.
AB  - A new prefabricated brace for the functional treatment of Colles' fractures has
      been developed. It is applied at fracture reduction and maintains fracture
      position by the application of three-point loading. In a prospective randomized
      clinical trial treating 85 displaced Colles' fractures, with blind independent
      follow-up, the brace gave better functional results than conventional plaster
      treatment. The improved function was apparent up to 6 months after injury. Finger
      function and pinch strength were also better in the brace-treated patients.
      Anatomical results were similar in the two groups.

PMID- 8550164
TI  - MRI in the management of tibial plateau fractures.
AB  - Twenty-one consecutive patients with fractures of the tibial plateau were
      investigated by standard radiography and magnetic resonance imaging (MRI) before
      treatment. It was found that MRI was more accurate in determining the
      classification of the fracture, in the identification of previously 'occult'
      fracture lines, and in accurate measurement of displacement and depression of
      fragments. This resulted in a change in the classification of 10 fractures (47.6
      per cent) and so a change in the management of four patients (19 per cent). In
      addition, MRI permits the reliable identification of associated intra- and
      periarticular soft tissue injuries pre-operatively for the first time in this
      group of injuries, seen to be present in 47.6 per cent of this series. This is
      higher than previously reported. No problems were encountered with the imaging
      technique, and in view of the significant effect on patient management, the
      authors now consider it to be the imaging method of choice.

PMID- 8550165
TI  - Diagnostic value of ultrasonography and conventional radiography for the
      assessment of sternal fractures.
AB  - This study compares the sonographic and conventional radiographic examination of
      sternal fractures. Forty-five patients with a suspected sternal fracture were
      examined radiographically and sonographically. Sixteen had a sternal fracture
      which could be identified sonographically. In 15 of the 16 cases an equivalent
      diagnosis could be made radiologically. In one case no definite statement could
      be made radiologically but the sonographic finding together with the clinical
      aspect of the patient proved the diagnosis of a fracture. In four sternal
      fractures displaced by more than one anteroposterior thickness, the fracture
      itself was shown by sonography whereas the extent of the injury could not be
      displayed. Ultrasonic investigation of the sternum is a useful way to demonstrate
      fractures that provides a similar sensitivity to conventional radiography. In
      contrast sonography is not suited for portraying the grade of displacement. In
      case of doubt after radiological examination the ultrasonic examination serves as
      a valuable tool but conventional plain radiography remains the standard means of
      documenting a sternal fracture.

PMID- 8550166
TI  - Abdominal wall haematoma mimicking visceral injury: the role of CT scanning.
AB  - Four patients are presented who were thought to have sustained visceral injury
      following blunt abdominal trauma. However, CT demonstrated abdominal wall
      haematomata and allowed nonoperative management. Similarity between the clinical
      findings in visceral injury and abdominal wall haematoma can lead to diagnostic
      difficulty. The cases illustrate the need to consider abdominal wall haematoma as
      a possible diagnosis in patients with blunt abdominal trauma. The place of CT in
      making this diagnosis is highlighted.

PMID- 8550167
TI  - Children with fractures ... should they attend school?

PMID- 8550168
TI  - How to minimize failures of fixation of unstable intertrochanteric fractures.
AB  - Sliding hip screws have improved the treatment of unstable intertrochanteric hip
      fractures and their success, compared with fixed devices, is in large part due to
      the sharing of load between the implant and the fracture fragments. In a
      prospective study of 100 patients with such fractures, five factors concerned
      with the fracture and its fixation were studied and odds ratios calculated of
      their relative importance in prediction of failure. The most important factor
      affecting the load borne by the fracture fragments was the amount of slide
      available within the device, and that affecting the load carried by the device
      was the position of the screw in the femoral head. For fractures fixed with a
      device allowing less than 10 mm of slide, and those with superior screw position,
      the risk of failure was increased by factors of 3.2 and 5.9, respectively.
      Anatomical reduction alone, rather than osteotomy, together with sliding hip
      screw fixation, has been recommended for these fractures in three prospective
      randomized trials. It is calculated here that to allow sufficient slide when
      employing this technique, it is essential to use a short barrel device when using
      dynamic screws of 85 mm or less. This has not been demonstrated before.

PMID- 8550169
TI  - Comparison of dynamic hip screw and gamma nail: a prospective, randomized,
      controlled trial.
AB  - We report a prospective, randomized, controlled trial, comparing the results of
      treatment with a dynamic hip screw (DHS) and a gamma nail in 95 consecutive
      patients with peri-trochanteric fractures of the femur. The DHS was used in 48
      patients, the gamma nail in 47. Clinical and radiological outcomes were similar,
      but the gamma nail was associated with a higher incidence of complications, in
      particular fracture of the femur below the implant in eight cases. This is
      consistent with previous reports, and we do not recommend the gamma nail for the
      treatment of peri-trochanteric femoral fractures.

PMID- 8550170
TI  - A non-union model of the rabbit tibial diaphysis.
AB  - A consistently reproducible non-union model has been created in the adult rabbit
      tibial diaphysis. After making an osteotomy, the marrow was removed, the
      periosteum was excised and a silastic sheath was wrapped around the shaft. The
      fracture cleft was invaded by a non osteogenic fibrous tissue following the
      removal of the sheath after an interval of 4 weeks.

PMID- 8550171
TI  - Electrical injuries: current concepts.
AB  - Electrical injuries are often dramatic accidents and are potentially fatal. The
      systemic involvement which characterizes many of these injuries, requires
      familiarity with the broad spectrum of clinical manifestations and possible
      complications. While many victims of electrocution are killed before help can be
      provided, survivors may suffer severe injuries that need proper treatment. The
      pathophysiological aspects of electrical injuries and therapeutic principles are
      therefore discussed in this review as well as preventive measures.

PMID- 8550172
TI  - Indirect lightning strike via telephone wire.

PMID- 8550173
TI  - Shotgun pellet embolus to the anterior cerebral artery.

PMID- 8550174
TI  - Late management of compartment syndromes.
AB  - Four patients have presented secondarily to this unit in recent years with
      rhabdomyolysis following prolonged compartment syndromes consequent upon drug
      overdoses or severe injury. Multiple complications arose due to the severe nature
      of the compartment syndrome itself and also its late and sometimes incomplete
      initial treatment. In two cases out of four a secondary amputation was required.
      Our experience with these cases demonstrates the importance of repeat examination
      under anaesthetic of the affected limbs following fasciotomy, even if apparently
      healthy granulation tissue is forming, and the value of persistent oedema and
      elevated creatine phosphokinase levels as markers of continued pathology.
      Observation of these factors may enable amputations and prolonged nerve palsies
      to be avoided in future patients.

PMID- 8550175
TI  - Fracture of the acromion associated with acromioclavicular dislocation.

PMID- 8550176
TI  - Fracture-dislocation of the shoulder with intrathoracic displacement of the
      humeral head.

PMID- 8550177
TI  - Os odontoideum--congenital or acquired?--that's not the question.

PMID- 8550178
TI  - An unusual case of irreducible intra-articular patellar dislocation with vertical
      axis rotation.

PMID- 8550179
TI  - Dislocation of the hip following intertrochanteric fracture.

PMID- 8550180
TI  - Incarcerated fragment of posterior acetabular wall fracture without hip
      dislocation.

PMID- 8550181
TI  - Cloning and sequence analysis of the pfl gene encoding pyruvate formate-lyase
      from Streptococcus mutans.
AB  - We have isolated a sorbitol-negative mutant of Streptococcus mutans GS-5
      following random mutagenesis with plasmid pVA891 clone banks. This mutant did not
      metabolize sorbitol anaerobically but did so aerobically. A 10-kb chromosomal DNA
      fragment flanking the pVA891 insertion was deleted in this mutant. The
      corresponding region from the parental strain GS-5 was then recovered by a marker
      rescue method with Escherichia coli. The pyruvate formate-lyase gene, pfl, was
      identified within a 3-kb PstI-XbaI fragment located in the middle of the deleted
      region of the chromosome, and its inactivation in S. mutans produced the same
      sorbitol-negative phenotype. Nucleotide sequence analysis of the pfl gene
      revealed a 2.3-kb open reading frame (ORF) preceded by potential ribosome-binding
      and promoter-like sequences. The ORF specified a putative protein of 775 amino
      acid residues with a calculated molecular weight of 87,533. The amino acid
      sequence deduced from the ORF exhibited significant similarity to that of the E.
      coli pfl gene.

PMID- 8550182
TI  - Membrane protein variations associated with in vitro passage of Borrelia
      burgdorferi.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, undergoes a loss in
      virulence with repeated passage in vitro. Defining the changes which occur after
      conversion to avirulence may assist in identifying virulence factors and
      mechanisms of pathogenesis. We have used a cross-adsorption technique and two
      dimensional nonequilibrium pH gradient electrophoresis to compare virulent (low
      passage) and avirulent (high-passage) variants of B. Burgdorferi B31. Using cross
      adsorbed rabbit sera to probe immunoblots, we identified 10 low-passage
      associated proteins (relative molecular masses of 78, 58, 49, 34, 33, 28, 24, 20,
      and 16 kDa) unique to the virulent strain B31. Cross-adsorbed human serum
      detected five proteins of similar sizes (78, 58, 34, 28, and 20 kDa), suggesting
      that several of of these proteins were expressed during human infection. By
      probing inner and outer membranes, two proteins (58 and 33 kDa) that localized
      specifically to the outer membrane were observed. An additional low-passage
      associated protein (28 kDa) was identified when outer membranes from low- and
      high-pressure variants of strain B31 were compared by two-dimensional
      nonequilibrium pH gradient electrophoresis.

PMID- 8550183
TI  - Selective induction of transforming growth factor beta in human monocytes by
      lipoarabinomannan of Mycobacterium tuberculosis.
AB  - The induction of macrophage-deactivating (interleukin-10 [IL-10] and transforming
      growth factor beta [TGF-beta] and macrophage-activating (IL-1, IL-6, and tumor
      necrosis factor alpha [TNF-alpha] cytokines by lipoarabinomannan (LAM) from
      pathogenic Mycobacterium tuberculosis Erdman and H37Rv strains (ManLAM) and
      nonpathogenic mycobacteria (AraLAM) in human blood monocytes was examined. ManLAM
      was significantly less potent in induction of TNF-alpha, IL-1, IL-6, and IL-10
      protein and mRNA, whereas its ability to induce TGF-beta was similar to that of
      AraLAM. Differences in induction of TNF-alpha mRNA by the two LAM preparations
      only became apparent at late time points of culture (24 h). The induction of TNF
      alpha and IL-1 by purified protein derivative of M. tuberculosis was
      significantly stronger than that by ManLAM. Pretreatment of monocytes with ManLAM
      did not, however, interfere with cytokine induction by lipopolysaccharide or
      AraLAM. The extensive mannosyl capping of arabinose termini of ManLAM may
      underlie the lack of ability to induce some cytokines (IL-1, TNF-alpha, and IL
      10) and the retained ability to induce TGF-beta. The latter may have a role in
      shifting the cytokine milieu in favor of survival of M. tuberculosis.

PMID- 8550184
TI  - Role of endotoxemia in cardiovascular dysfunction and lethality: virulent and
      nonvirulent Escherichia coli challenges in a canine model of septic shock.
AB  - We investigated whether the severity of septic shock is determined by virulence
      factors associated with or the levels of endotoxemia produced by two Escherichia
      coli strains. Canines were challenged intraperitoneally with an E. coli strain
      (O6:H1:K2) that has virulence factors associated with human disease or with an
      equal dose of a nonvirulent strain (O86:H8) that lacks these factors. Both
      strains were administered in viable, heat-killed, and purified endotoxin forms.
      Median survival times with the virulent strain compared with the nonvirulent
      strain were shorter with viable bacteria (5 x 10(10) CFU/kg) (144 h versus > 672
      h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(9) CFU/kg) ( >
      676 h versus 26 h; P = 0.03), and similar with purified endotoxin (15 mg/kg) (28
      h versus 48 h; P = 0.71). However, whether the challenge contained viable
      bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain
      produced less endotoxemia (P = 0.001). Hence, the changing outcomes with
      differing forms of the two strains cannot be attributed solely to endotoxin
      levels. The viable virulent strain caused less endotoxemia but more harm, and
      this does not appear to be explained by a more potent endotoxin or other heat
      stable component. This study suggests that circulating endotoxin levels per se
      are less important in the outcome of septic shock than virulence factors
      associated with E. coli strains. Furthermore, the data call into question the
      significance of the endotoxin concentration in the blood in predicting the
      severity of shock and the lethality of gram-negative infections.

PMID- 8550185
TI  - An oxygen-induced but protein F-independent fibronectin-binding pathway in
      Streptococcus pyogenes.
AB  - Protein F is an important fibronectin-binding adhesin of Streptococcus pyogenes
      (group A streptococcus). However, all previous analyses of protein F have been
      conducted in a mutant strain which expresses protein F under anaerobic conditions
      nonpermissive for expression in other strains. In this study, we have examined
      the fibronectin-binding properties of several protein F-deficient mutants
      cultured under aerobic conditions and have identified a second pathway for
      binding fibronectin. Unlike the case with protein F, exposure to an aerobic
      environment does not induce transcription of a new gene product. Rather, O2 is
      apparently required for the modification of a protease-resistant cell surface
      component into a binding-component form. Modification occurred preferentially at
      a pH of 6.0 or less, and the binding of the modified component to fibronectin
      required Zn2+. The oxidizing agent Fe(CN)6 could be substituted for O2 and
      stimulated expression of binding activity under O2-limiting conditions.
      Streptococcal fibronectin binding mediated by this pathway but not by protein F
      could be inhibited by laminin and by streptococcal lipoteichoic acid, a molecule
      previously implicated as the streptococcal adhesin for fibronectin. The non
      protein F-binding activity could also substantially enhance the binding of the
      organism for fibronectin. The non-protein F-binding activity could also
      substantially enhance the binding of the organism to basement membrane. By using
      differential inhibition, analyses of binding to non-protein F mutant strains
      demonstrated that the total level of fibronectin bound under aerobic conditions
      reflects contributions from both pathways. Because of its dependence on Zn2+, an
      oxidant, and pH, this binding activity has been designated the ZOP binding
      pathway.

PMID- 8550186
TI  - Passive immunization with monoclonal antibodies against Porphyromonas gingivalis
      in patients with periodontitis.
AB  - Selective inhibition of recolonization of Porphyromonas gingivalis was
      investigated by topical application of monoclonal antibody (MAb). To select a MAb
      to P. gingivalis with the potential for recognizing most strains of P.
      gingivalis, we examined seven MAbs, one of which (MAb 61BG 1.3) recognized all 22
      laboratory strains and serotypes of P. gingivalis tested as well as 105 human
      clinical isolates. A comparative study of the number of P. gingivalis bacteria
      identified by conventional culture and immunofluorescence with MAb 61BG 1.3
      showed a very significant correlation between the two methods (Spearman r = 0.85,
      P < 0.001). Fourteen patients with periodontitis, who harbored P. gingivalis in
      their subgingival plaque, were treated by root planing and with metronidazole to
      suppress any detectable P. gingivalis. In this double-blind study, the patients
      were then divided randomly into two groups; one was treated with MAb to P.
      gingivalis, and the other was treated with saline. Each patient had four
      subgingival applications of 3 micrograms of MAb (or saline) per tooth at 1, 3, 7,
      and 10 days after P. gingivalis was suppressed. The number of P. gingivalis
      bacteria was then monitored, and significantly less recolonization of the sites
      with the most severe periodontitis was found in the MAb-treated patients than in
      the control patients (P < 0.01). This was evident at 6 and 9 months after the
      application of MAb, but by 12 months, P. gingivalis, was also found to recolonize
      these sites in two of the MAb-treated patients. The effect of MAb was specific to
      P. gingivalis, since the numbers of spirochetes were not significantly different
      between the two groups. However, no significant difference in any clinical
      periodontal indices between the immunized and control patients at 6 and 12 months
      was observed. This is the first demonstration that a putative periodontal
      pathogen can be selectively prevented from recolonization for up to 9 months in
      sites with the most severe periodontitis. This strategy could be used to
      establish directly in humans whether a microorganism is involved in the
      pathogenesis of periodontitis, by repeated application of the corresponding MAb
      at about 6-month intervals and by comparing the clinical indices between the MAb
      treated and control patients.

PMID- 8550187
TI  - Nonadherent cultures of human monocytes kill Mycobacterium smegmatis, but
      adherent cultures do not.
AB  - Human peripheral blood monocytes are permissive for the growth of Mycobacterium
      tuberculosis, but the fate of nonpathogenic Mycobacterium smegmatis in these
      cells is not known. Since M. smegmatis may be used as a host with which to
      express and screen for M. tuberculosis genes needed for survival in monocytes, we
      determined whether human peripheral blood monocytes could restrict the growth of
      Mycobacterium smegmatis. Adherent human peripheral blood monocytes were
      permissive for the growth of M. smegmatis, as measured by ex vivo [3H]uracil
      uptake. However, human peripheral blood monocytes which were cultured
      nonadherently in Teflon wells were able to restrict the growth of M. smegmatis
      while remaining permissive for the growth of M. tuberculosis H37Ra. The loss of
      viability of M. smegmatis in nonadherent cells was correlated with an increase in
      nonspacious phagocytic vacuoles. The killing of M. smegmatis was not blocked by
      NG-monomethyl-L-arginine, suggesting that it was not due to the production of
      reactive nitrogen intermediates. Incubation of the monocytes for 1 to 7 days
      before infection had no effect on the fate of M. smegmatis, suggesting that
      adherence versus nonadherence, and not differentiation, was the key determinant
      for the difference in functional ability. Nonadherent human peripheral blood
      monocytes may be a more appropriate model than adherent cells for the study of
      factors employed by bacterial to survive within monocytes and for selection
      screening of bacterial genes needed for intracellular survival.

PMID- 8550188
TI  - Identification of murine protective epitopes on the Porphyromonas gingivalis
      fimbrillin molecule.
AB  - Fimbriae from Porphyromonas gingivalis are believed to play an important role in
      the pathogenesis of periodontal diseases. The aim of the present study was to
      identify the fimbrial protective T-cell epitopes in CBA/J mice. A truncated
      protein corresponding to amino acids 1 to 198, PgF1-198, was generated and
      allowed us to demonstrate that the N terminus of the protein contains T-cell
      epitopes. With synthetic peptides, an immunodominant sequence was identified
      between amino acids 103 and 122. The corresponding peptide, PgF-P8, induced T
      cell proliferation after in vitro restimulation of in vivo-primed cells, giving a
      stimulation index comparable to the one obtained with r-fimbrillin, and induced
      production of both Th1 and Th2 cytokines. Growth supernatant contained
      significant levels of interleukin 2 (IL-2), gamma interferon, IL-4 (28 pg/ml),
      and tumor necrosis factor alpha. Immunization of mice with r-fimbrillin, PgF1
      198, and PgF-P8 induced production of antibodies specific to r-fimbrillin and PgF
      P8. In addition, by using the mouse chamber model we found that mice immunized
      with PgF-P8 were dramatically protected against a normally lethal injection of P.
      gingivalis. Animals immunized with PgF-P8 40 days prior to challenge showed a 60%
      survival rate when challenged with P. gingivalis, compared with just 25% survival
      in control animals and just 5% survival in mice immunized with PgF-P8 only 21
      days prior to challenge. Although the protection depended on the time of
      immunization before the bacterial challenge, it did not correlate with in vivo
      local cytokine production (IL-2, IL-4, IL-6, tumor necrosis factor alpha, and
      gamma interferon), specific antibody levels, or the isotype of anti-PgF-P8
      antibodies produced.

PMID- 8550189
TI  - Mycoplasma arthritidis mitogen up-regulates human NK cell activity.
AB  - While the effects of superantigens on T lymphocytes are well characterized, how
      superantigens interact with other immune cells is less clear. This report
      examines the effects of Mycoplasma arthritidis mitogen (MAM) on human natural
      killer (NK) cell activity. Incubation of peripheral blood mononuclear cells
      (PBMC) with MAM for 16 to 20 h augmented NK cytotoxicity (against K562) in a dose
      dependent manner (P < or = 0.05). Superantigen-dependent cellular cytotoxicity,
      an activity of superantigen-activated cytotoxic T cells, was not involved in
      lysis of K562 cells because the erythroleukemic tumor target cells expressed no
      class II major histocompatibility complex by fluorescence-activated cell sorter
      analysis. Kinetic experiments showed that the largest increase in NK activity
      induced by MAM occurred within 48 h. Incubation with MAM caused a portion of NK
      cells to become adherent to tissue culture flasks, a quality associated with
      activation, and augmented NK activity was found in both adherent and nonadherent
      subpopulations. Experiments using cytokine-specific neutralizing antibodies
      showed that interleukin-2 contributed to enhancement of the NK activity observed
      in superantigen-stimulated PBMC. Interestingly, MAM was able to augment NK lysis
      of highly purified NK (CD56+) cells in the absence of other immune cells in 9 of
      12 blood specimens, with the augmented lytic activity ranging from 110 to 170% of
      unstimulated NK activity. In summary, data presented in this report show for the
      first time that MAM affects human NK cells directly by increasing their lytic
      capacity and indirectly in PBMC as a consequence of cytokines produced by T
      cells. Results of this work suggest that, in vivo, one consequence of interaction
      with superantigen-secreting microorganisms may be up-regulation of NK lytic
      activity. These findings may have clinical application as a means of generating
      augmented NK effector cells useful in the immunotherapy of parasitic infections
      or neoplasms.

PMID- 8550190
TI  - Influence of monocytes and antibiotic treatment on tissue factor activity of
      endocardial vegetations in rabbits infected with Streptococcus sanguis.
AB  - A main feature in the pathogenesis of bacterial endocarditis is the activation of
      the coagulation system via the extrinsic pathway, resulting in the formation of
      infected endocardial vegetations. Earlier studies gave indirect evidence that
      monocytes play an important role in the procoagulant response during the course
      of the disease. In this study, we assessed the role of monocytes more directly.
      We compared weights and tissue factor activities (TFA) of endocardial vegetations
      of normal rabbits infected with Streptococcus sanguis with those of rabbits which
      were treated with the cytostatic drug etoposide (Vepesid; Bristol-Myers Squibb
      B.V.) to induce a selective monocytopenia. Furthermore, the importance of the
      presence of bacteria was determined through the influence of antibiotic treatment
      on TFA, vegetational weight, and infection of the vegetations. The TFA of the
      vegetations was measured chromogenically by monitoring the factor VII-dependent
      activation of factor X with an amidolytic assay for factor Xa. We found that the
      degree of infection and the weight of vegetations of rabbits treated with the
      cytostatic drug etoposide did not differ from that of untreated rabbits. Their
      TFA, however, was significantly lower than the TFA of vegetations of rabbits not
      treated with etoposide. We also found that, as with the monocytopenic rabbits,
      the weight of the vegetations was not reduced in penicillin G-treated rabbits.
      The degree of infection and TFA, however, were significantly lower. We conclude
      that monocytes indeed are involved in the activation of the coagulation system
      during the course of bacterial endocarditis and that the degree of infection is
      positively correlated to the TFA of the vegetations.

PMID- 8550191
TI  - H2O2 induces monocyte apoptosis and reduces viability of Mycobacterium avium-M.
      intracellulare within cultured human monocytes.
AB  - Mycobacterium avium-M. intracellulare, an intracellular parasite of mononuclear
      phagocytes, rarely causes disease in immunocompetent individuals. In contrast, in
      human immunodeficiency virus type 1-infected patients, M. avium-M. intracellulare
      can infect almost every tissue and organ. This suggests that immunocompetent
      individuals have a protective mechanism to control or prevent the infection. How
      mycobacterial may be killed by the host immune response is unclear. We have
      recently reported that induction of apoptosis of Mycobacterium bovis BCG-infected
      macrophages with ATP4- was associated with killing of the intracellular
      mycobacteria. In the present study, a long-term culture of M. avium-M.
      intracellulare-infected monocytes was used to further evaluate the interaction
      between M. avium-M. intracellulare and primary human monocytes. In our system, M.
      avium-M. intracellulare parasitized the human monocytes and appeared to replicate
      slowly over 14 days within the host cells. To examine the role of apoptotic
      mechanisms in survival or death of intracellular mycobacteria, M. avium-M.
      intracellulare-infected human monocytes were treated with a monoclonal antibody
      to Fas receptor (APO-1/CD95) or with various concentrations of H2O2. Although
      both of these exogenous agents induced monocyte apoptosis, optimal killing (65%
      reduction in CFU) of intracellular M. avium-M. intracellulare was observed only
      when M. avium-M. intracellulare-infected cells were treated with 10 mM H2O2. Fas
      induced apoptosis did not affect M. avium-M. intracellulare viability. Our
      results suggest that not all stimuli of monocyte apoptosis induce killing of
      intracellular M. avium-M. intracellulare. Since release of H2O2 following
      phagocytosis of mycobacteria has been documented, H2O2-induced apoptotic death of
      M. avium-M. intracellulare-infected monocytes and its association with killing of
      the intracellular bacilli may be a physiological mechanism of host defense
      against M. avium-M. intracellulare.

PMID- 8550192
TI  - Physical linkage of the Vibrio cholerae mannose-sensitive hemagglutinin secretory
      and structural subunit gene loci: identification of the mshG coding sequence.
AB  - Vibrio cholerae O1 expresses a variety of cell surface factors which mediate
      bacterial adherence and colonization at the intestinal epithelium. The mannose
      sensitive hemagglutinin (MSHA), a type IV pilus, is a potential attachment factor
      of the V. cholerae El Tor biotype. We describe a TnphoA mutant that is defective
      in its ability to hemagglutinate mouse erythrocytes. The TnphoA insertion maps to
      a recently identified genetic locus that encodes products that are predicted to
      be essential for assembly and export of the MSHA pilus. Insertional disruption at
      this locus in a mshA-phoA reporter strain provides evidence for a role of this
      locus in the latter stages of pilus assembly and/or export. These constructs have
      provided physical markers by which we have established close physical linkage of
      this secretion locus to a set of genes that includes the mshA structural gene.
      Sequence analysis of the intervening region between these two loci has revealed
      the presence of an open reading frame with homology to pilus biogenesis genes of
      several gram-negative bacteria. This genetic organization suggests an entire
      operon encoding the MSHA pilus and the components necessary for its assembly and
      secretion to the bacterial cell surface. The nomenclature of the MSHA structural
      and secretory locus has been redefined accordingly.

PMID- 8550193
TI  - Elevated aspartic proteinase secretion and experimental pathogenicity of Candida
      albicans isolates from oral cavities of subjects infected with human
      immunodeficiency virus.
AB  - Isolates of Candida albicans from the oral cavities of subjects at different
      stages of human immunodeficiency virus (HIV) infection or uninfected controls
      were examined for (i) production of aspartic proteinase(s), a putative virulence
      associated factor(s); (ii) the presence in the fungal genome of two major genes
      (SAP1 and SAP2) of the aspartic proteinase family; and (iii) experimental
      pathogenicity in a murine model of systemic infection. It was found that the
      fungal isolates from symptomatic patients secreted, on average, up to eightfold
      more proteinase than the isolates from uninfected or HIV-infected but
      asymptomatic subjects. This differential property was stably expressed by the
      strains even after years of maintenance in stock cultures. Moreover,
      representative high-proteinase isolates were significantly more pathogenic for
      mice than low-proteinase isolates of C. albicans. The characters high proteinase
      and increased virulence were not associated with a single molecular type or
      category identifiable through DNA fingerprinting or pulsed-field electrophoretic
      karyotype, and both SAP1 and SAP2 genes were present in both categories of
      isolates, on the same respective chromosomes. In conclusion, our data suggest
      that during HIV infection more-virulent strains or biotypes of C. albicans which
      are identifiable by direct analysis of virulence determinants are selected. It
      also appears that the biotype switch to increased aspartic proteinase and
      virulence properties occurs before the HIV-infected subject enters the
      symptomatic stage and overt AIDS.

PMID- 8550194
TI  - Sequence analysis of the chromosomal region around and within the V-1-encoding
      gene of Mycoplasma pulmonis: evidence for DNA inversion as a mechanism for V-1
      variation.
AB  - Although the variation of V-1 antigens of Mycoplasma pulmonis has been correlated
      with variable expression of the cytadherence properties of this organism and has
      been implicated as a virulence determining factor in M. pulmonis-induced murine
      respiratory disease, the precise function of these antigens remains unknown. We
      have cloned and characterized genes encoding V-1 from two M. pulmonis UAB CT V-1
      variants that differ in hemadsorption properties. A comparison of the nucleotide
      sequences revealed that these two variant genes were identical in the 5'-most 724
      nucleotides. Regions of extensive divergence that contained repeated sequences
      were found 3' to this conserved region. On the basis of their deduced amino acid
      sequences, one variant expressed a V-1 protein of 94.2 kDa presumptively
      containing 40 repeats of 17 amino acids and the other expressed a protein of 27.4
      kDa consisting 2 direct, noncontiguous 9-amino-acid repeats. These general
      properties, as well as the presence of a prokaryotic lipoprotein acylation
      sequence (L-X-Y-C), indicated that the genes encoding V-1 were similar in
      structure to genes encoding other mycoplasma surface lipoproteins. Further
      analysis of sequences flanking these genes revealed that these variants arose via
      an inversion event which provided an interchange of the two variable regions as
      well as for the conserved region of these genes and immunoblot analyses using
      rabbit polyclonal antibodies specific for synthetic peptides derived from the
      sequences of the different variable regions indicated that DNA inversion acted as
      a switch which allowed only one of the two different genes to be expressed at any
      given time. This inversion model clearly provides a mechanism by which M.
      pulmonis can alter its surface architecture and also strongly suggests that the
      as-yet-undefined function of V-1 residues in the variable carboxy region of these
      proteins.

PMID- 8550195
TI  - Functional analysis of pneumolysin by use of monoclonal antibodies.
AB  - We have produced a panel of monoclonal antibodies to pneumolysin, the membrane
      damaging toxin from Streptococcus pneumoniae. We have used these antibodies to
      identify three regions of the toxin sequence that are involved in the lytic
      mechanism of this toxin. Two of these sites probably form the cell binding site
      of this toxin. Antibodies to the third site inhibit the lytic action of this
      toxin but not the binding of this toxin to cells. This site is engaged in the
      oligomerization process involved in the formation of pores in cell membranes. Two
      of these epitopes are also present in the related toxin perfringolysin O.

PMID- 8550196
TI  - A novel 95-kilodalton antigen of Wuchereria bancrofti infective larvae identified
      by species-specific monoclonal antibodies.
AB  - CBA and BALB/c mice produced polyspecific and monospecific polyclonal antibody
      responses, respectively, following immunization with Wuchereria bancrofti stage-3
      larvae. Two monoclonal antibodies (MAbs) were produced from the immunized BALB/c
      mouse. These MAbs (both isotype M) recognized a previously undescribed highly
      expressed W. bancrofti antigen present in stage-3 larvae. The epitopes bound by
      the MAbs appear to be species specific for W. bancrofti since the MAbs did not
      bind to antigens of either nine other nematode species or two vector species in
      Western blots (immunoblots). Phosphorylcholine epitopes, responsible for
      immunological cross-reactivity among nematodes, were identified only on a 200-kDa
      antigen and not on the 95-kDa molecule. The targets of these immunoglobulin M
      MAbs are not carbohydrate epitopes.

PMID- 8550197
TI  - Orally administered microencapsulated Bordetella pertussis fimbriae protect mice
      from B. pertussis respiratory infection.
AB  - Fimbriae from Bordetella pertussis have been encapsulated in poly(lactide-co
      glycolide) microparticles of a size appropriate for uptake by the immune
      inductive tissues of the gastrointestinal tract. Mice were immunized by oral
      gavage with a single dose of 10 micrograms of microencapsulated fimbriae. The
      resulting immune responses were compared with those resulting from
      intraperitoneal injection of mice with equivalent amounts of fimbriae absorbed
      onto alhydrogel. The examination of serum and mucosal secretions, collected over
      a 6-week period, for specific antifimbrial antibodies clearly demonstrated that
      only orally immunized animals mounted measurable immune responses in external
      secretions. Six weeks after immunization, all immunized animals were protected
      against intranasal challenge with live B. pertussis.

PMID- 8550199
TI  - C5a peptidase alters clearance and trafficking of group A streptococci by
      infected mice.
AB  - Group A streptococcal C5a peptidase (SCPA) specifically cleaves the human serum
      chemotaxin C5a at the polymorphonuclear leukocyte (PMNL) binding site. This study
      tested the proposal that SCPA contributes to virulence by retarding the influx of
      inflammatory cells and clearance of streptococci during the first few hours after
      infection. To investigate the specific contribution of SCPA to the virulence of
      group A streptococci, scpA insertion and deletion mutants were created by
      directed plasmid insertion into scpA and gene replacement. The precise locations
      of insertion and deletion mutations were confirmed by PCR and DNA sequence
      analysis. The impact of mutation on virulence was investigated with a mouse air
      sac model of inflammation. Experiments evaluated clearance of streptococci from
      the air sac within 4 h after infection. SCPA- streptococci were cleared more
      efficiently than wild-type bacteria. Localization of streptococci in lymph nodes
      and spleens of infected mice revealed a significant difference between mutant and
      wild-type streptococci. PMNLs and other granulocytes that infiltrated the air sac
      were quantitated by single-color flow cytometry. The total cellular infiltrate
      was greater and PMNLs dominated the granulocytic infiltrates of air sacs
      inoculated with SCPA- mutant bacteria. The data obtained are consistent with the
      possibility that SCPA- streptococci are initially cleared from the site of
      infection primarily by PMNLs. Moreover, mutant and wild-type streptococci
      followed different paths of dissemination. SCPA- bacteria were transported to
      lymph nodes, whereas wild-type streptococci avoided transport to the lymph nodes
      and rapidly spread to the spleen.

PMID- 8550198
TI  - Regulation of the Shiga-like toxin II operon in Escherichia coli.
AB  - Investigations of the regulation of the bacteriophage-encoded Shiga-like toxin II
      (SLT-II) in Escherichia coli demonstrated that bacteriophages exhibit a
      regulatory impact on toxin production by two mechanisms. Firstly, replication of
      the toxin-converting bacteriophages brings about an increase in toxin production
      due to concomitant multiplication of toxin gene copies. Secondly, an influence of
      a phage-encoded regulatory molecule was demonstrated by using low-copy-number
      plasmid pADR-28, carrying a translational gene fusion between the promoter and
      proximal portion of slt-IIA and the structural gene for bacterial alkaline
      phosphatase (phoA). PhoA activity, reflecting the slt-II promoter activity, was
      significantly enhanced in E. coli strains which and been lysogenized with an SLT
      I or SLT-II-converting bacteriophage (H-19B or 933W, respectively) or
      bacteriophage lambda. Both mechanisms are dependent on bacteriophage induction
      and hence are recA dependent. Moreover, the study revealed that the DNA-binding
      protein H-NS has a regulatory impact on both bacteriophage-mediated SLT-II
      synthesis and the activity of the slt-II promoter of plasmid pADR-28. While a
      slight impact of growth temperature on SLT-II expression was observed, no impact
      of either osmolarity, pH, oxygen tension, acetates, iron level, or utilized
      carbon source could be demonstrated.

PMID- 8550200
TI  - Lack of cleavage of IcsA in Shigella flexneri causes aberrant movement and allows
      demonstration of a cross-reactive eukaryotic protein.
AB  - Once in the cytoplasm of mammalian cells, Shigella flexneri expresses a motile
      phenotype caused by polar directional assembly of actin. This process depends on
      accumulation of IcsA (VirG), a 120-kDa protein with ATPase activity, at the pole
      of the bacterium opposite to that at which ongoing septation occurs. IcsA is also
      secreted into the bacterial supernatant as a 95-kDa species, after cleavage at an
      SSRRASS sequence which, when mutagenized, blocks processing. MAbF15, an anti-IcsA
      monoclonal antibody, recognizes an epitope located within repeated Gly-rich boxes
      in the N-terminal half of the protein. We used this monoclonal antibody to
      visualize the location of a noncleavable 120-kDa IcsA mutant protein expressed in
      S. flexneri. We found that this noncleavable IcsA protein no longer localized
      exclusively to the pole of the bacterium but also could be detected
      circumferentially. Whereas the monoclonal antibody detected the wild-type
      cleavable form of IcsA in only 40% of the cells expressing this protein, the
      noncleavable was easily detectable in all the cells carrying the icsA mutant
      allele. Similar aberrant localization of the IcsA mutant protein on bacteria
      growing within the cytoplasm of HeLa cells was observed. The strains expressing
      the noncleavable IcsA protein expressed abnormal intracellular movement and were
      often observed moving in a direction perpendicular to their longitudinal axis.
      The putative protease which processes IcsA may therefore play a role in achieving
      polar expression of this protein and providing maximum asymmetry essential to
      directional movement. In addition, MAbF15 allowed us to identify a 70-kDa
      eukaryotic protein cross-reacting with IcsA. This protein accumulated in the
      actin tails of motile bacteria and in membrane ruffles of the cells.

PMID- 8550201
TI  - Pyoverdin is essential for virulence of Pseudomonas aeruginosa.
AB  - The role of pyoverdin, the main siderophore in iron-gathering capacity produced
      by Pseudomonas aeruginosa, in bacterial growth in vivo is controversial, although
      iron is important for virulence. To determine the ability of pyoverdin to compete
      for iron with the human iron-binding protein transferrin, wild-type P. aeruginosa
      ATCC 15692 (PAO1 strain) and PAO pyoverdin-deficient mutants were grown at 37
      degrees C in bicarbonate-containing succinate medium to which apotransferrin had
      been added. Growth of the pyoverdin-deficient mutants was fully inhibited
      compared with that of the wild type but was restored when pyoverdin was added to
      the medium. Moreover, when growth took place at a temperature at which no
      pyoverdin production occurred (43 degrees C), the wild-type PAO1 strain behaved
      the same as the pyoverdin-deficient mutants, with growth inhibited by
      apotransferrin in the presence of bicarbonate and restored by pyoverdin
      supplementation. Growth inhibition was never observed in bicarbonate-free
      succinate medium, whatever the strain and the temperature for growth. In vivo, in
      contrast to results obtained with the wild-type strain, pyoverdin-deficient
      mutants demonstrated no virulence when injected at 10(2) CFU into burned mice.
      However, virulence was restored when purified pyoverdin originating from the wild
      type strain was supplemented during the infection. These results strongly suggest
      that pyoverdin competes directly with transferrin for iron and that it is an
      essential element for in vivo iron gathering and virulence expression in P.
      aeruginosa. Rapid removal of iron from [59Fe]ferritransferrin by pyoverdin in
      vitro supports this view.

PMID- 8550202
TI  - Furin regulates both the activation of Pseudomonas exotoxin A and the Quantity of
      the toxin receptor expressed on target cells.
AB  - Pseudomonas exotoxin A (PE) binds and enters mammalian cells via the alpha 2
      macroglobulin receptor/low density lipoprotein receptor-related protein (LRP).
      The toxin then requires proteolytic cleavage to generate an enzymatically active
      fragment with translocates to the cell cytosol and inhibits protein synthesis. To
      assess the role of furin in determining toxin susceptibility, CHO cells were
      transfected with a mouse furin gene (CHO+fur cells) and maintained under neomycin
      selection. Cells expressing the transfected gene were about two- to threefold
      more sensitive to PE than were cells expressing only a neomycin resistance gene
      (CHO+neo cells). Possible reasons for the increased toxin sensitivity include the
      cleavage of a greater number of PE molecules and/or the conversion of more single
      chain LRP to the processed, two-chain form. Processing of LRP appears to be
      necessary to allow the surface display of this receptor. Results of ligand
      binding studies indicated that the CHO+fur cells displayed about twofold more
      surface-expressed LRP than did CHO+neo cells. In addition, the in vitro cleavage
      of PE by recombinant furin enhanced toxin potency about threefold for CHO+neo
      cells but enhanced it very little for CHO+fur cells. This suggested that CHO+fur
      cells were processing PE at close to the maximum usable rate. Together these
      findings suggest that furin is involved in at least two separate protein
      processing pathways that each contribute to the sensitivity of cells to PE.

PMID- 8550203
TI  - Bacterial enzymes can add galactose alpha 1,3 to human erythrocytes and creates a
      senescence-associated epitope.
AB  - Humans have abundant circulating anti-alpha (1,3-di)-galactosyl (alpha Gal)
      antibodies (anti-Gal). Anti-Gal has been implicated in the clearance of senescent
      human erythrocytes (RBCs). The nature of the anti-Gal-binding RBC epitope has
      defied explanation, given that humans repress expression of the alpha 1,3
      galactosyltransferase (alpha 1,3 GT) enzyme. This study explored whether alpha
      Gal epitopes on human RBCs might be synthesized by alpha 1,3 GTs of bacterial
      origin that are translocated into the circulation during commensal colonization
      of the gut by gram-negative bacteria. We found that an acellular Klebsiella
      pneumoniae sonicate could add 3H-UDP-Gal to human RBCs in the alpha configuration
      at 37 degrees C in the presence of 6 mM MnCl2 (pH 7.6). Gradient anion-exchange
      chromatography of the Klebsiella sonicate yielded four fractions that could
      catalyze the addition of 3H-Gal to human RBCs. Size-exclusion chromatography of
      these anion-exchange fractions yielded peaks of high GT activity for each, but
      only those derived from the first, third, and last anion-exchange fractions
      incorporated Gal such that the RBCs bound anti-Gal by fluorescence-activated cell
      sorter, suggesting that these three GTs are alpha 1,3 GTs. Thus, Klebsiella spp.
      make at least four GTs that can add an alpha Gal to human cell surface acceptor
      structures. Three of these GTs can form alpha 1,3 Gal structures on human RBCs
      that bind anti-Gal, thereby creating "autoimmune" senescence-associated RBC
      epitopes.

PMID- 8550204
TI  - A Th1-associated increase in tumor necrosis factor alpha expression in the spleen
      correlates with resistance to blood-stage malaria in mice.
AB  - We investigated the kinetics of tissue-specific mRNA expression and systemic
      production of tumor necrosis factor alpha (TNF-alpha) and the kinetics of splenic
      expression of mRNAs of gamma interferon (INF-gamma) and interleukin-4 (IL-4),
      cytokines that may regulate TNF-alpha production, during the early phase of blood
      stage infection with Plasmodium chabaudi AS. Northern blot analysis revealed that
      resistant C57BL/6 mice, which clear the infection by 4 weeks, had higher levels
      of TNF-alpha mRNA in the spleen and liver early during infection that did
      susceptible A/J mice, which succumb to the disease 10 days after initiation of
      infection. Treatment of resistant mice with a polyclonal anti-TNF-alpha antibody
      confirmed the protective role of TNF-alpha early during the course of infection.
      Furthermore, resistant C57BL/6 mice also expressed high levels of mRNA of IFN
      gamma (a Th1 marker) and low levels of mRNA of IL-4 (a Th2 marker) in the spleen,
      whereas susceptible A/J mice had low levels of IFN-gamma mRNA but high levels of
      TNF-alpha mRNA in the liver and had high levels of TNF-alpha protein in serum, as
      measured by enzyme-linked immunosorbent assay, later during infection just before
      death occurred. These results demonstrate that a Th1-associated increase in TNF
      alpha mRNA expression in the spleen early during infection correlates with
      resistance to P. chabaudi AS, whereas increased TNF-alpha mRNA levels in the
      liver and excessive levels of the TNF-alpha protein in serum later during
      infection correlate with susceptibility. Thus, the role of the TNF-alpha during
      malaria appears to depend on the timing and site of its expression and the
      presence of cytokines regulating its production.

PMID- 8550205
TI  - The major outer membrane protein of a single Chlamydia trachomatis serovar can
      possess more than one serovar-specific epitope.
AB  - The major outer membrane proteins (MOMPs) of human Chlamydia trachomatis serovars
      exhibit four regions of variable amino acid sequences (VS1 to VS4) harboring
      serovar-specific B-cell epitopes. Antibody responses to these epitopes may
      contribute to acquired protection against human chlamydial infection. MOMP B-cell
      epitopes defined by 22 different serovar-specific or bispecific murine monoclonal
      antibodies were localized with synthetic peptides representing the four VS
      regions of seven genital serovars (D, Da, E, F, G, H, and K). Serovar F possessed
      two distinct serovar-specific epitopes, located in VS2 and VS4, while serovar K
      possessed three distinct serovar-specific epitopes, located in VS1, VS2, and VS4.
      Serovar D- and serovar Da-specific epitopes were located in VS1. Regardless of
      whether the serovar was from the B (serovars D, Da, and E), C (serovars H and K),
      or F-G (serovars F and G) serogroup, all serovar-specific epitopes were found in
      three discrete subgroups of MOMPs. These subregions comprised all central portion
      of VS1, residues 70 to 77; the amino-terminal half of VS2, residues 139 to 149;
      and the carboxyl-terminal third of VS4, residues 305 to 315. Monoclonal
      antibodies to each of these subregions neutralized infectivity in standard HaK
      cell culture assays. These findings are relevant to the development of an MOMP or
      MOMP subunit vaccine.

PMID- 8550207
TI  - Pathogenicity of Theileria parva is influenced by the host cell type infected by
      the parasite.
AB  - Theileria parva has been shown to infect and transform B cells and T cells at
      similar frequencies in vitro. However, the majority of parasitized cells in the
      tissues of infected cattle are alpha/beta T cells. The aim of this study was to
      determine whether the cell type infected with T. parva influenced the
      pathogenicity of the parasite. The initial approach, which involved inoculation
      of cattle with autologous cloned cell lines of different phenotypes, failed to
      resolve the issue, because of prolonged period of culture required to clone and
      characterize the cell lines resulted in attenuation of the cells. As an
      alternative approach, cattle were inoculated with purified populations of
      autologous cells that had been incubated in vitro with T. parva sporozoites for
      48 h. As few as 3 x 10(4) peripheral blood mononuclear cells (PBMC) treated in
      this way were found to produce severe clinical reactions with high levels of
      parasitosis. Infections of similar severity were produced with purified
      populations of CD2+, CD4+, and CD8+ T cells. By contrast, infected B cells gave
      rise to mild self-limiting infections even when administered at a 10-fold-higher
      dose. In animals that received infected CD4+ or CD8+ T cells, the parasitized
      cells in the lymph nodes on day 11 of infection were all within the CD4+ and CD8+
      populations, respectively, indicating that there had been minimal transfer of the
      parasite between cell types. Phenotypic analyses of cultures of PBMC infected in
      vitro with saturating concentrations of sporozoites revealed that parasitized B
      cells were abundant in the cultures after 1 week but were subsequently overgrown
      by T cells. The results of these experiments indicate that the cell type infected
      by T. parva influences the pathogenicity of the parasite.

PMID- 8550206
TI  - Variation of Brucella abortus 2308 infection in BALB/c mice induced by prior
      vaccination with salt-extractable periplasmic proteins from Brucella abortus 19.
AB  - The study compared the immune and protective responses induced in BALB/c mice
      vaccinated with six salt-extractable periplasmic protein fractions (Brucella cell
      surface proteins [BCSP]) of Brucella abortus 19 and later challenge exposed with
      B. abortus 2308. BCSP70 was precipitated with ammonium sulfate at 70% saturation,
      and BCSP100 was precipitated with ammonium sulfate at 100% saturation by use of
      supernatant fluid of BCSP70 that had been precipitated with 70% ammonium sulfate.
      Four subfractions were separated from BCSP100 by anion-exchange high-performance
      liquid chromatography (HPLC). Monophosphoryl lipid A (MPL) from Salmonella
      typhimurium Re mutant strain was used as a potential immune response modifier in
      some vaccines. Reduced or increased numbers of CFU and increased spleen size in
      the principal groups of mice relative to that of the nonvaccinated control group
      were considered protectiveness or virulence (survival) criteria. Results
      indicated that vaccines prepared from BCSP70 and BCSP100 were moderately
      protective and immunogenic. The subfractions designated BCSP100-A through BCSP100
      D purified by anion-exchange HPLC were not protective when MPL was not used as an
      immune response modifier. However, two subfractions were associated with
      significant (P < 0.05) increases in CFU per spleen and splenomegaly in vaccinated
      mice compared with those in nonvaccinated challenge-exposed mice. MPL enhanced
      protection or was neutral when used with BCSP70, BCSP100, BCSP100-C, and BCSP100
      D. Serologic results of an enzyme-linked immunosorbent assay indicated that MPL
      modulated the immunoglobulin G responses induced by BCSP70, BCSP100, and
      subfraction BCSP100-B vaccines only. The overall results suggest that certain
      proteinaceous periplasmic fractions might serve as virulence or survival factors
      in B. abortus infections.

PMID- 8550208
TI  - Pathogenicity and cytadherence of Mycoplasma imitans in chicken and duck embryo
      tracheal organ cultures.
AB  - Two strains of the avian organism Mycoplasma imitans were examined for
      pathogenicity and cytadherence in chicken and duck embryo tracheal organ
      cultures, and a virulent strain of the related pathogen Mycoplasma gallisepticum
      was included for comparison. All consistently cause ciliostasis in tracheal
      explants from both hosts, and examination of infected tissues by
      immunofluorescence and transmission electron microscopy demonstrated that M.
      imitans proliferated on the epithelial surface and adhered to the respiratory
      epithelium by means of its terminal tip structure in the same manner as M.
      gallisepticum. These observations endorse the striking phenotypic similarities
      between M. imitans and M. gallisepticum and suggest that M. imitans may have
      pathogenic potential in vivo.

PMID- 8550209
TI  - Influence of beta 2-microglobulin expression on gamma interferon secretion and
      target cell lysis by intraepithelial lymphocytes during intestinal Listeria
      monocytogenes infection.
AB  - Numerous microbial pathogens, including Listeria monocytogenes, enter the host
      through the intestine. Although relatively little is known about the biological
      functions of intestinal intraepithelial lymphocytes (i-IEL), they are generally
      considered a first line of defense against intestinal infections. In the mouse,
      the vast majority of i-IEL express the CD8 coreceptor either as a CD8 alpha/alpha
      homodimer or as a CD8 alpha/beta heterodimer. The CD8 receptor of T-cell receptor
      TcR gamma/delta i-IEL is exclusively homodimeric, whereas the CD8-expressing TcR
      alpha/beta i-IEL segregate into equal fractions of CD8 alpha/alpha and CD8
      alpha/beta cells. We infected beta 2-microglobulin (beta 2m)+/- mice (possessing
      all i-IEL populations) and beta 2m -/- mutant mice (lacking all CD8 alpha/beta +
      i-IEL and having few CD8 alpha/alpha + TcR alpha/beta i-IEL) with L.
      monocytogenes per os and determined their biological functions after TcR ligation
      with monoclonal antibodies. Cytolytic activities of TcR alpha/beta and TcR
      gamma/delta i-IEL from beta 2m +/- mice were not influenced by intestinal
      listeriosis. Cytolytic activities of TcR alpha/beta i-IEL were impaired in
      uninfected beta 2m -/- mice, but this reduction was reestablished as a
      consequence of intestinal listeriosis. Frequencies of gamma interferon (IFN
      gamma)-producing TcR alpha/beta i-IEL in uninfected beta 2m -/- mice were
      reduced, compared with that in their heterozygous controls. Equally low
      frequencies of IFN-gamma-producing TcR gamma/delta i-IEL in beta 2M +/- and beta
      2m-/- mutants were found. Listeriosis increased frequencies of INF-gamma
      producing TcR alpha/beta and TcR gamma/delta i-IEL in both mouse strains. Most
      remarkably, the proportion of IFN-gamma-producing TcR gamma/delta i-IEL was
      elevated 10-fold in listeria-infected beta 2M -/- mice. Our findings show that
      the beta 2m-independent CD8 beta- i-IEL expressing either TcR alpha/beta or TcR
      gamma/delta are stimulated by intestinal listeriosis independent of regional beta
      2m expression. We conclude that the three major CD8+ i-IEL populations are
      stimulated by intestinal listeriosis and that CD8 beta- i-IEL compensate for the
      total lack of CD8 beta+ i-IEL in beta 2M -/- mutant mice. Hence, in contrast to
      the peripheral immune system, which crucially depends on CD8 alpha/beta + TcR
      alpha/beta lymphocytes, the mucosal immune system can rely on additional
      lymphocytes expressing the CD8 alpha/alpha homodimer.

PMID- 8550210
TI  - Development of Shigella sonnei live oral vaccines based on defined rfbInaba
      deletion mutants of Vibrio cholerae expressing the Shigella serotype D O
      polysaccharide.
AB  - Previous experimentation has highlighted a number of difficulties in the
      development of carrier-based bivalent vaccines (J.-F. Viret and D. Favre,
      Biologicals 22:361-372, 1994) In an attempt to obviate these carrier strains.
      Toward this aim, a series of defined rfbInaba deletion (delta rfbInaba) mutants
      of the cholera vaccine strain V. cholerae CVD103-HgR (O1 Inaba serotype) and
      derivative bearing the chromosomally integrated locus encoding the S. sonnei O-PS
      were constructed and characterized. The various mutations disrupt genes thought
      to be involved in either the synthesis of perosamine, the synthesis of 3-deoxy-L
      glycero tetronic acid, or the O-PS transport functions together with synthesis of
      the perosamine synthetase. Some deletions were obtained only in strains
      expressing the heterologous lipopolysaccharide (LPS). Viable delta rfbInaba
      deletions in CVD103-HgR profoundly altered some of its phenotypic properties. The
      same deletions present in CVD103-HgR derivatives expressing the heterologous LPS
      affected their phenotypes only to a lesser extent. Only in strains in which
      perosamine synthesis was specifically abolished could high amounts of core-bound
      S. sonnei O-PS be synthesized. Two such strains (CH21, which expresses both the
      R1 core and the S. sonnei O-PS, and CH22, which expresses only the latter
      antigenic determinant) were further analyzed and were found to be
      indistinguishable from CVD103-HgR with regard to lack of enterotoxin activity,
      choleragenoid production, mercury resistance, pilin production, and, for CH22,
      motility. Mice immunized with CH22 produced high titers of S. sonnei O-PS
      specific antibodies.

PMID- 8550211
TI  - Streptococcus salivarius urease: genetic and biochemical characterization and
      expression in a dental plaque streptococcus.
AB  - The hydrolysis of urea by urease enzyme of oral bacteria is believed to have a
      major impact on oral microbial ecology and to be intimately involved in oral
      health and diseases. To begin to understand the biochemistry and genetics of oral
      ureolysis, a study of the urease of Streptococcus salivarius, a highly ureolytic
      organism which is present in large numbers on the soft tissues of the oral
      cavity, has been initiated. By using as a probe a 0.6-kpb internal fragment of
      the S. salivarius 57.I ureC gene, two clones from subgenomic libraries of S.
      salivarius 57.I in an Escherichia coli plasmid vector were identified. Nucleotide
      sequence analysis revealed the presence of one partial and six complete open
      reading frames which were most homologous to ureIAB-CEFGD of other ureolytic
      bacteria. Plasmid clones were generated to construct a complete gene cluster and
      used to transform E. coli and Streptococcus gordonii DL1, a nonureolytic, dental
      plaque microorganism. The recombinant organisms expressed high levels of urease
      activity when the growth medium was supplemented with NiCl2. The urease enzyme
      was purified from E. coli, and its biochemical properties were compared with
      those of the urease produced by S. salivarius and those of the urease produced by
      S. gordonii carrying the plasmid-borne ure genes. In all cases, the enzyme had a
      Km of 3.5 to 4.1 mM, a pH optimum near 7.0, and a temperature optimum near 60
      degrees C. S. gordonii carrying the urease genes was then demonstrated to have a
      significant capacity to temper glycolytic acidification in vitro in the presence
      of concentrations of urea commonly found in the oral cavity. The ability to
      genetically engineer plaque bacteria that can modulate environmental pH through
      ureolysis will open the way to using recombinant ureolytic organisms to test
      hypotheses regarding the role of oral ureolysis in dental caries, calculus
      formation, and periodontal diseases. Such recombinant organisms may eventually
      prove useful for controlling dental caries by replacement therapy.

PMID- 8550212
TI  - Pertussis toxin-catalyzed ADP-ribosylation of Gi-2 and Gi-3 in CHO cells is
      modulated by inhibitors of intracellular trafficking.
AB  - In previous studies, an in vitro ADP-ribosylation assay was developed to
      quantitatively evaluate the in vivo ADP-ribosylation of eukaryotic target
      proteins in intact Chinese hamster ovary (CHO) cells by pertussis toxin (PT).
      Immunoblot analysis identified the two PT-sensitive target proteins in CHO cells
      as Gi-2 and Gi-3. In this in vitro ADP-ribosylation assay, the ability of PT and
      ADP-ribosylate Gi-2 and Gi-3 intact CHO cells was not inhibited by cytochalasin D
      but was inhibited by chloroquine, monensin, and nocodazole. These data implicated
      the involvement of a cytochalasin D-independent endocytic mechanism, a pH
      sensitive step, and microtubules in the ADP-ribosylation of Gi-2 and Gi-3 by PT
      in intact CHO cells. Preincubation of CHO cells with cycloheximide, at
      concentrations that reduced protein synthesis by > 95%, did not inhibit the
      ability of PT to ADP-ribosylate Gi-2 and Gi-3. Control experiments showed that
      these agents did not affect either the ability of PT to directly ADP-ribosylate
      the heterotrimeric G protein, Gt, or the binding of PT to CHO cells, except that
      monensin slightly inhibited the binding of PT to CHO cells. These results are
      consistent with a model in which PT is internalized by receptor-mediated
      endocytosis, probably via a cytochalasin D-independent pathway, which involves
      intracellular trafficking through late endosomes and the Golgi apparatus. An
      alternative model predicts the presence of a eukaryotic factor that traffics
      within cells via this pathway and is required by PT to ADP-ribosylate Gi
      proteins.

PMID- 8550213
TI  - Pseudomonas aeruginosa strains possess specific adhesins for laminin.
AB  - Pseudomonas aeruginosa is a major human pathogen known to infect tissues that
      have been previously damaged in some way. In wounded human respiratory tissues,
      P. aeruginosa cells were found attached to exposed basement membranes following
      epithelial denudation, suggesting that the affinity for extracellular matrix
      proteins may account for the bacterium's opportunistic character. By using
      microtiter wells coated with different P. aeruginosa strains, we demonstrated
      that laminin binds to both colonizing bacterial strains, isolated from
      asymptomatic carriers, and strains isolated from infected patients. Binding of
      soluble laminin to piliated P. aeruginosa PAK and to the nonpiliated isogenic
      mutant PAK/p--was shown to be saturable. Binding of laminin to the piliated PAK
      strain was not different from binding to th nonpiliated PAK/p--strain but was
      significantly higher than binding to the avirulent, nonpiliated PAK-N1 rpoN
      mutant. By transmission electron microscopy, we localized the laminin-binding
      sites on a loose material in the outermost layer of the bacteria. Western
      immunoblotting results suggested that 57- and 59-kDa nonpilus adhesins from the
      microbial outer membranes account for the binding of P. aeruginosa to laminin. We
      speculate that bacterial affinity for laminin may be of biological significance
      in the pathogenesis of P. aeruginosa infection of injured tissues.

PMID- 8550214
TI  - Transferrin associated with the porcine intestinal mucosa is a receptor specific
      for K88ab fimbriae of Escherichia coli.
AB  - Putative receptors of Escherichia coli K88 fimbriae are either tightly membrane
      bound or an integral part of membranes. Thus, proteins associated with piglet
      small intestinal mucosae were solubilized by a detergent (deoxycholate). A 74-kDa
      glycoprotein (GP74) purified from enterocyte and brush border membrane
      preparations was specifically detected in vitro by K88ab fimbriae. GP74 was
      recognized only in the mucosae of phenotypically adhesive animals. Metaperiodate
      treatment abolished the recognition, indicating that K88ab fimbriae-GP74 binding
      required the carbohydrate moiety. This glycoprotein belongs to the transferrin
      family and differed from the serum transferrin of the same adhesive-phenotype
      piglets. Unlike intestinal transferrin, serum transferrin was recognized
      independently of the adhesion phenotype. The glycan moieties of intestinal and
      serum transferrins differed in their molar compositions. Transferrin GP74
      contained one monosialylated and monofucosylated glycan chain of the N
      acetyllactosamine type. Intestinal holotransferrin exhibited pI values of 5.2,
      5.3, 5.5, and 5.6, whereas serum holotransferrin pI values ranged between 5.4 and
      6.2. Since mucosal transferrin was found intimately entrapped on membranes, we
      hypothesize that a K88ab fimbriae-transferrin-cell transferrin receptor complex
      might allow the bacteria to adhere to specific sites of the mucosa.

PMID- 8550215
TI  - Rapid cyclic changes in density and accessibility of endometrial ligands for
      Escherichia coli Dr fimbriae.
AB  - The mechanisms of developing infection in young, noncompromised individuals are
      well understood. Colonization is prerequisite for the development of infection.
      In human, ligands serving bacterial colonization belong to common antigens.
      Consequently, a majority of individuals should be sensitive to infection at all
      times. We hypothesize that the temporal patterns of some infections and
      sensitivity to them are associated with sudden changes in the density and
      accessibility of common receptors. Endometrial samples from women having normal
      menstrual cycles were examined for histological location, receptor density, and
      in situ hybridization of Dr (decaying-accelerating factor) ligands for
      Escherichia coli Dr fimbriae. Significant up-regulation and luminal expression of
      Dr ligands occurred during the secretory phase, whereas receptors were expressed
      in the basement membrane and in smaller quantities during the proliferative
      phase. This observation agrees with our hypotheses that some ligands recognized
      by bacterial adhesins change their compartmentalization and, most importantly,
      that they up-regulate expression at specific times.

PMID- 8550217
TI  - Role of sulfatides in adhesion of Helicobacter pylori to gastric cancer cells.
AB  - We have demonstrated that clinical isolates of Helicobacter pylori preferentially
      bind to sulfatides (I3SO3-GalCer) and GM3 gangliosides (II3NeuAcLacCer), two
      predominant acidic glycosphingolipids in the human gastric mucosa, on thin-layer
      chromatography plates. However, it has not yet been clarified that these
      glycospingolipids truly serve as adhesion receptors for H. pylori in live cells.
      In this study, we used a gastric cancer cell line, KATO III, as a cellular model
      of H. pylori adhesion and examined the role of sulfatides in attachment. The
      adhesion of H. pylori (i.e., a standard strain of H. pylori, NCTC 11637) to KATO
      III cells and the effects of various substances on this adhesion were monitored
      and semiquantitated by flow cytometric analysis. Sulfated glycoconjugates, such
      as heparin and gastric mucin, significantly inhibited H. pylori adhesion to KATO
      III cells. Membrane preparations from KATO III cells strongly inhibited this
      adhesion. In the membrane preparations, sulfatides were present as a major acidic
      glycosphinoglipid. With the exception of sulfatides, no distinct adhesion of H.
      pylori to glycospingolipids from KATO III cells were observed. Moreover, H.
      pylori did not bind to any membrane proteins of KATO III cells. Finally, a
      monoclonal anti-sulfatide antibody markedly reduced H. pylori adhesion to KATO
      III cells. These results suggest that sulfatides, and possibly related sulfated
      compounds, serve as a major receptor for cell adhesion by H. pylori.

PMID- 8550216
TI  - Monoclonal immunoglobulin A derived from peritoneal B cells is encoded by both
      germ line and somatically mutated VH genes and is reactive with commensal
      bacteria.
AB  - We transferred peritoneal cells from BALB/c mice into C.B17 scid/scid mice. Six
      to eight months after injection, only cells with the B1 phenotype were retained
      in the spleens and peritoneal cavities of these mice. The lamina propria of the
      intestine contained many peritoneal, donor-derived, immunoglobulin A (IgA)
      producing cells. The mesenteric lymph nodes of these mice were found to be a
      major site of proliferation and generation of IgA plasmablasts. We established
      eight IgA-producing hybridomas from the mesenteric lymph nodes of such mice, and
      all the hybridomas reacted with different but partially overlapping fecal
      bacterial populations. Cloning and sequencing of the VH genes of these hybridomas
      showed that two hybridomas utilized germ line-encoded VH genes while the VH genes
      of the six hybridomas showed somatic mutations, some of which are indicative of
      an antigen-driven selection process.

PMID- 8550218
TI  - Legionella pneumophila mutants that are defective for iron acquisition and
      assimilation and intracellular infection.
AB  - Legionella pneumophila, a parasite of macrophages and protozoa, requires iron for
      optimal extracellular and intracellular growth. However, its mechanisms of iron
      acquisition remain uncharacterized. Using mini-Tn10 mutagenesis, we isolated 17
      unique L. pneumophila strains which appeared to be defective for iron acquisition
      and assimilation. Eleven of these mutants were both sensitive to the iron
      chelator ethylenediamine di(o-hydroxyphenylacetic acid) and resistant to
      streptonigrin, an antibiotic whose lethal effect requires high levels of
      intracellular iron. Six mutants were also defective for the infection of
      macrophage-like U937 cells. Although none were altered in entry, mutants
      generally exhibited prolonged lag phases and in some cases replicated at slower
      rates. Overall, the reduced recoveries of mutants, relative to that of the wild
      type, ranged from 3- to 1,000-fold. Strain NU216, the mutant displaying the most
      severe lag phase and the slowest rate of replication, was studied further.
      Importantly, within U937 cells, NU216 was approximately 100-fold more sensitive
      than the wild type was to treatment with the Fe3+ chelator deferoxamine,
      indicating that it is defective for intracellular iron acquisition and
      assimilation. Furthermore, this strain was unable to mediate any cytopathic
      effect and was impaired for infectivity of an amoebal host. Taken together, the
      isolation of these mutants offers genetic proof that iron acquisition and
      assimilation are critical for intracellular infection by L. pneumophila.

PMID- 8550219
TI  - Mycoplasma membrane lipoproteins induced proinflammatory cytokines by a mechanism
      distinct from that of lipopolysaccharide.
AB  - To gain a clear understanding of the mechanisms by which mycoplasmas induced the
      expression of proinflammatory cytokines in monocytic cells, we have studied the
      induction of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, and IL
      6 by mycoplasmas in three distinct human myelomonocytic cell lines in comparison
      with induction by lipopolysaccharide (LPS). HL-60 cell line did not release
      cytokines when induced with either LPS or mycoplasmas. In contrast to LPS,
      mycoplasmas failed to increase the weak levels of tumor necrosis factor alpha
      secreted by phorbol myristate acetate-differentiated U937 cells. In addition,
      Northern (RNA) blot analysis of cytokine expression in these cells showed that
      the induction of IL-1 beta by mycoplasmas involves, unlike that by LPS,
      posttranscriptional events. Interestingly, in THP-1 cells, cytokine induction
      pathways triggered by mycoplasmas remained operational under conditions where LPS
      pathways were abolished, suggesting functional independence. The study of
      cytokine-inducing activity displayed by distinct fractions derived from a series
      of different mycoplasma species demonstrated that lipid membrane constituents
      were largely responsible for these effects. Finally, we have demonstrated that
      tyrosine phosphorylation is a crucial event in the mycoplasma-mediated induction
      of proinflammatory cytokines in either THP-1 cells or human monocytes.

PMID- 8550220
TI  - Assembly and antigenicity of the Neisseria gonorrhoeae pilus mapped with
      antibodies.
AB  - The relationship between the sequence of Neisseria gonorrhoeae pilin and its
      quaternary assembly into pilus fibers was studied with a set of site-directed
      antibody probes and by mapping the specificities of antipilus antisera with
      peptides. Buried and exposed peptides in assembled pili were identified by
      competitive immunoassays and immunoelectron microscopy with polyclonal antibodies
      raised against 11 peptides spanning the pilin sequence. Pili did not compete
      significantly with pilin subunits for binding to antibodies against residues 13
      to 31 (13-31) and 18-36. Pilus fibers competed well with pilin protein subunits
      for binding to antibodies raised against peptides 37-56, 58-78, 110-120, 115-127,
      122-139, and 140-159 and competed weakly for antibodies against residues 79-93
      and 94-108. Antibodies to sequence-conserved residues 37-56 and to semiconserved
      residues 94-108 preferentially bound pilus ends as shown by immunoelectron
      microscopy. The exposure of pilus regions to the immune system was tested by
      peptide mapping of antiserum specificities against sets of overlapping peptides
      representing all possible hexameric or octameric peptides from the N. gonorrhoeae
      MS11 pilin sequence. The immunogenicity of exposed peptides incorporating
      semiconserved residues 49-56 and 121-126 was revealed by strong, consistent
      antigenic reactivity to these regions measured in antipilus sera from rabbits,
      mice, and human and in sera from human volunteers with gonorrhea. The
      conservation and variation of antigenic responses among these three species
      clarify the relevance of immunological studies of other species to the human
      immune response against pathogens. Overall, our results explain the extreme
      conservation of the entire N-terminal one-third of the pilin protein by its
      dominant role in pilus assembly: hydrophobic residues 1-36 are implicated in
      buried lateral contacts, and polar residues 37-56 are implicated in longitudinal
      contacts within the pilus fiber.

PMID- 8550221
TI  - The N-terminal half of membrane CD14 is a functional cellular lipopolysaccharide
      receptor.
AB  - CD14, a glycosylphosphatidylinositol-anchored protein on the surface of
      monocytes, macrophages, and polymorphonuclear leukocytes, is a receptor for
      lipopolysaccharide (LPS). It was recently reported that an N-terminal 152-amino
      acid fragment of soluble CD14 was an active soluble lipopolysaccharide receptor
      (T. S. -C. Juan, M. J. Kelley, D. A. Johnson, L. A. Busse, E. Hailman, S. D.
      Wright, and H. S. Lichenstein, J. Biol. Chem. 270:1382-1387, 1995). To determine
      whether the N-terminal half of the membrane CD14 was a functional LPS receptor on
      the cell membrane, we engineered a chimeric gene coding for amino acids 1 to 151
      of CD14 fused to the C-terminal region of decay-accelerating factor and expressed
      it in Chinese hamster ovary cells and 70Z/3 cells. We found that the chimeric,
      truncated CD14 is a fully functional LPS receptor in both cell lines.

PMID- 8550222
TI  - Structural characteristics of peptidoglycan fragments required to prime mice for
      induction of anaphylactoid reactions by lipopolysaccharides.
AB  - Structural characteristics of peptidoglycan fragments required to prime mice for
      the induction of anaphylactoid reactions by Salmonella abortusequi
      lipopolysaccharide were examined in endotoxin-resistant C3H/HeJ mice, with
      special focus on the disaccharide-pentapeptide [N-acetylglucosaminyl-beta(1-4)-N
      acetylmuramyl-L-alanyl-D -isoglutaminyl-meso-2,6-diaminopimelyl (DAP)-D-alanyl-D 
      alanine] and its smaller partial derivatives. The bacterial and synthetic muramyl
      tripeptides (DAP- and lysine [Lys]-type, respectively) and synthetic muramyl
      dipeptide primed mice for induction of anaphylactoid reactions accompanied by
      death within 1 h. The disaccharide-tripeptide exhibited weaker activity, and the
      disaccharide-tetrapeptide and muramyl tetrapeptide exhibited marginal activity.
      In contrast, intact peptidoglycans of various bacteria and the disaccharide
      pentapeptide lacked the priming activity, although they showed adjuvant activity
      similar to that of the above components.

PMID- 8550223
TI  - Porphyromonas gingivalis FDC381 multiplies and persists within human oral
      epithelial cells in vitro.
AB  - Porphyromonas gingivalis FDC381 replication and persistence within KB epithelial
      cells in vitro were studied by means of an antibiotic protection assay and
      electron microscopy. Intracellular counts decreased during the first 24 h; showed
      a threefold increase during the second day, indicating intracellular
      multiplication; and after 8 days declined to levels approximating 40% of the
      initial invasion. The ability of P. gingivalis to persist and multiply within
      epithelial cells may constitute a pathogenic mechanism in periodontal disease.

PMID- 8550225
TI  - Interaction of Legionella pneumophila with Acanthamoeba castellanii: uptake by
      coiling phagocytosis and inhibition of phagosome-lysosome fusion.
AB  - Legionella pneumophila is a facultative intracellular parasite able to survive
      within both human monocytes and amoebae. We have demonstrated that processing of
      L. pneumophila by the free-living amoeba Acanthamoeba castellanii shows many
      similarities to the processing of L. pneumophila by monocytes. These similarities
      include uptake of L. pneumophila by coiling phagocytosis and the subsequent
      confinement of L. pneumophila in a ribosome-studded phagosome. In addition, as in
      monocytes, inhibition of lysosomal fusion with phagosomes containing L.
      pneumophila was detected in amoebae. With all clinical isolates, inhibition of
      phagosomes-lysosome fusion correlated with virulence. However, with one of the
      environmental isolates tested, no significant difference in phagosome-lysosome
      fusion was observed between the virulent and avirulent forms. These results
      indicate that the avirulent form of this isolate differed from the virulent form
      in some other respect critical to intracellular survival. Therefore,
      intracellular multiplication of L. pneumophila within A. castellanii may not be
      solely dependent upon the inhibition of lysosomal fusion.

PMID- 8550224
TI  - Persistence of serum and salivary antibody responses after oral immunization with
      a bacterial protein antigen genetically linked to the A2/B subunits of cholera
      toxin.
AB  - Primary oral immunization of mice with a bacterial protein antigen genetically
      coupled to the A2 and B subunits of cholera toxin induced specific secretory
      immunoglobulin A and serum immunoglobulin G antibodies that persisted at
      substantial levels for at least 11 months. A subsequent single booster
      immunization did not further enhance the antibody responses. Long-term antibody
      persistence may be especially important in infections caused by common pathogens
      for which continuous immunity would be advantageous.

PMID- 8550226
TI  - Listeriolysin is a potent inducer of the phosphatidylinositol response and lipid
      mediator generation in human endothelial cells.
AB  - The impact of Listeria monocytogenes listeriolysin O (LLO) secretion on
      phosphoinositide metabolism and mediator (platelet-activating factor and
      prostaglandin I2) generation was investigated in human umbilical vein endothelial
      cells. Wild-type L. monocytogenes, purified LLO, and an L. innocua strain
      engineered to secrete LLO all elicited a strong response, whereas mutant strains
      defective in LLO production were ineffective. Thus, human umbilical vein
      endothelial cell stimulation by listeriae is linked to production of LLO.

PMID- 8550227
TI  - Immunogenicity of group B Streptococcus type III polysaccharide-tetanus toxoid
      vaccine in baboons.
AB  - Maternal vaccination has been proposed as a rational approach for the prevention
      of neonatal group B streptococcal (GBS) disease. In this study, baboons were used
      as a nonhuman primate model to evaluate the immunogenicity of a GBS type III
      glycoconjugate vaccine. Type III-specific immunoglobulin G with opsonic activity
      was induced after vaccination with type III polysaccharide coupled to tetanus
      toxoid administered with an aluminum adjuvant. This suggests that baboons could
      be used in evaluating maternal transfer of GBS-specific antibodies by vaccination
      during pregnancy.

PMID- 8550229
TI  - Evaluation of infantilizing intonation and content of speech directed at the
      aged.
AB  - Infantilization was investigated in a sample of thirty-five elderly adults, both
      community residents (N = 18) and residents of institutions (N = 17). Respondents
      were presented with materials designed to elicit ratings of adult and
      infantilized speech content and intonation on the dimensions of "likeability,"
      "equality of treatment," and "degree of respect." Community and institutionalized
      elders rated adult speech in an equivalent fashion. However, community residents
      were more negative in their ratings of infantilizing speech content and
      intonation compared to their ratings of adult speech than were institutionalized
      elders. The negative regard that community elders had for infantilizing speech
      was particularly pronounced for intonation. Furthermore, community elders
      appeared particularly resentful of infantilizing speech intonation on the
      dimension of respect. There was no evidence to support the contention that
      infantilizing speech is high in nurturance. Adding to the findings of Ryan and co
      workers, it appeared important to differentiate between infantilizing content and
      intonation, as the infantilizing intonation produced a more pronounced negative
      reaction than did infantilizing content among community elders.

PMID- 8550228
TI  - Structure and regulation of the Hsp90 gene from the pathogenic fungus Candida
      albicans.

PMID- 8550230
TI  - Centenarians: their memories and future ambitions.
AB  - Research investigating how the recall of one's past functions in maintaining
      psychological well-being and/or adaptation to the aging process is widely
      scattered and generally inconclusive with regard to significant findings. One way
      to address the lack of a systematic research thrust is to replicate previous
      work. The purpose of the study reported herein was to replicate Costa and
      Kastenbaum's 1967 study of the relationship between past memories and future
      ambitions of centenarians using data from the Georgia Centenarian Study. Ninety
      seven centenarians and 189 eighty- and sixty-year-olds were asked the same four
      questions as found in the Costa and Kastenbaum study. Contrary to Costa and
      Kastenbaum's results, no significant relationship was found between the ability
      to recall three types of past events and being able to conceive of the future in
      the Georgia study. Other similarities and differences in findings between the two
      studies are discussed.

PMID- 8550231
TI  - Human development in the context of aging and chronic illness: the role of
      attachment in Alzheimer's disease and stroke.
AB  - Does chronic illness in older people provide potentials for human development? To
      date, this question has not been adequately addressed by dynamic theorists of
      human development. In this article, two illness trajectories, Alzheimer's disease
      and stroke, are examined to illustrate emerging changes in human development over
      each course of illness and the increasing importance of attachment behavior among
      ill elders and their family members. It is argued that the phenomenon of
      attachment links ailing older people to their environment, and that attachment is
      vital if human development is to continue.

PMID- 8550232
TI  - Variability in daily events and mood of family caregivers to cognitively impaired
      elders.
AB  - This study explores the relationship of daily mood and daily events in a
      caregiving context. Family caregivers to demented elders (N = 43) kept fourteen
      day diaries of: 1) caregiving activities, 2) disruptive patient behaviors, and 3)
      daily mood. Independent raters and cluster analysis support the hypothesis of
      three mood patterns. Differences among the three clusters in the relationship of
      mood and daily caregiving events were explored. The findings indicate that some
      caregivers are highly distressed by caregiving demands, some report moderate
      levels of distress, and others show no relationship between mood and daily
      events. The varied patterns support an individual differences approach to
      understanding caregiving and in the design of interventions.

PMID- 8550233
TI  - Correlates of reminiscence activity among elderly individuals.
AB  - The purpose of this study was to examine several psychological characteristics
      and life experiences that may be related to aspects of reminiscence activity
      among elderly individuals. Seventy elderly individuals completed a reminiscence
      questionnaire assessing 1) the extent to which reminiscence is motivated by a
      desire to enhance self understanding, 2) reminiscence affect, and 3) the
      preferred social modality of reminiscence. The respondents also completed
      questionnaires assessing existential vacuum, extraversion, and the recent
      experience of various life events. Existential vacuum was positively associated
      with a tendency to engage in reminiscence in an effort to enhance self
      understanding as well as a negative bias in reminiscence affect. Extra-version
      was found to be positively related to a preference for interpersonal
      reminiscence. Specific life experiences (e.g., death of a spouse, retirement)
      were also related to reminiscence activity. The present results provide support
      for the notion that aspects of reminiscence activity are associated with
      individual differences in specific psychological and situational variables.

PMID- 8550234
TI  - Changing the way we talk with elders: promoting health using the communication
      enhancement model.
AB  - Good communication is an essential component of optimal delivery of health care
      and health promotion efforts. In this article, we address the communication
      predicament faced by older adults when their opportunities for optimal care are
      limited by inappropriate communication with formal care providers. We then
      introduce the Communication Enhancement Model which promotes health in old age by
      stressing recognition of individualized cues, modification of communication to
      suit individual needs and situations, appropriate assessment of the health/social
      problems, and empowerment of both elders and providers. Applications of the
      Communication Enhancement Model are discussed for two high-risk groups (elders
      from ethnocultural communities and elders with dementia) to show how it can
      function as a guide for the development and evaluation of educational
      interventions with health and social professionals working with elders.

PMID- 8550235
TI  - Microsatellite instability and alterations in the hMSH2 gene in human ovarian
      cancer.
AB  - The role of the replication error-positive (RER+) phenotype in the development of
      specific subtypes of sporadic ovarian carcinomas was examined by screening for
      the presence of microsatellite instability (MI) in 47 tumors. The overall
      frequency of ovarian MI was 17% only. However, MI occurred in 50% of the ovarian
      endometrioid-type tumors, which was significantly more often than in all the
      other histological subtypes combined (8%). Five of the 8 RER+ tumors exhibited
      most marked type I instability, possibly representing a different mechanism than
      for the remaining type 2 tumors. The cDNA of the mutation suppression gene hMSH2,
      the gene most often associated with MI, was screened for alterations in 8 MI
      positive and 5 MI-negative ovarian tumors. Only 3 changes were found. Complete
      loss of hMSH2 mRNA expression was detected in I tumor, while another expressed
      only an abnormal transcript containing a deletion of exon 3. One additional RER+
      serous adenocarcinoma contained a rare polymorphism with a non-conservative amino
      acid change. One of 8 RER+ tumors showed loss of heterozygosity at the hMSH2
      loci. Genetic instability, caused in part by alterations in the hMSH2 gene, may
      play an important role in the sporadic endometrioid subtype of ovarian tumors.
      Other mutator-phenotype genes may be responsible for the remaining cases of RER+
      ovarian tumors.

PMID- 8550236
TI  - E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded
      tissues: correlation with histopathological grade, tumour stage and survival.
AB  - To determine the potential prognostic value of epithelial cadherin (E-cadherin),
      a Ca(2+)-dependent cell-cell adhesion molecule, we have analysed its
      immunoreactivity and cellular localisation in 67 transitional cell carcinomas
      (TCC) using an avidin-biotin immunoperoxidase technique on formalin-fixed,
      paraffin-embedded tissues. These results were correlated with histopathological
      grade, tumour stage, presence of metastases and survival. In addition, 10
      cystitis and 11 normal bladder biopsies were evaluated as controls. E-cadherin
      was expressed in a normal membranous pattern in all normal and 7 of 10 cystitis
      biopsies. Loss of normal surface E-cadherin expression was found in 3 of 15
      superficial tumours and in 48 of 52 invasive cancers. Abnormal immunoreactivity
      was strictly related to tumour differentiation and stage. Fifteen of 20 well
      differentiated (grade I) tumours showed preserved membranous E-cadherin
      immunoreactivity, while 46 of 47 moderate and poorly differentiated tumours
      (grades II and III) demonstrated abnormal staining patterns. Loss of membranous E
      cadherin immunoreactivity was also associated with advanced tumour stage. There
      was a significantly higher 5-year survival rate for patients with preserved
      membranous staining compared with patients with abnormal staining.

PMID- 8550237
TI  - Frequency and prognostic evaluation of 3p21-22 allelic losses in non-small-cell
      lung cancer.
AB  - Previous loss of heterozygosity (LOH) studies of chromosome 3p loci have
      displayed a 60% deletion frequency in non-small-cell lung cancers (NSCLC), as
      opposed to small-cell lung cancers, in which the 3p deletion is consistently
      found. However, the high stromal-cell admixture found in NSCLC and the use of the
      Southern-blot method lead to under-evaluation of this frequency. In this study,
      we used a very precise microdissection technique followed by PCR amplification of
      6 3p21-22 polymorphic genomic sequences to analyze LOH in 86 NSCLC and in normal
      adjacent tissue. We found the sensitivity of the microdissection-PCR-based LOH
      technique higher than the sensitivity of the Southern-blot technique: 87% of the
      squamous-cell carcinomas and 84% of the large-cell undifferentiated carcinomas
      showed a clear LOH for a 3p21-22 locus. All doubly informative cases but 4 showed
      concordant deletion at all 3p21-22 loci. The analysis of 3p microsatellite
      sequences displayed only 2 cases of genomic instability, one of them also
      displaying features of tumoral heterogeneity as regards the instability genotype.
      Four carcinomas in situ adjacent to these NSCLC showed the same allelic profile
      as the invasive tumors. The only prognostic factors in this study were the
      disease stage and histology. The 3p21-22 deletion was not related to the stage of
      the disease and did not appear to be a significant prognostic factor of survival.
      3p21 loss appears, so far, to be the most frequent and the earliest genetic
      alteration described in NSCLC, but does not seem to carry significant prognostic
      information in invasive tumors.

PMID- 8550238
TI  - Loss of heterozygosity on chromosome 9 in human breast cancer: association with
      clinical variables and genetic changes at other chromosome regions.
AB  - Primary breast tumors were tested for loss of heterozygosity (LOH), on chromosome
      9p with microsatellite markers restricted to a 28 cM region including the MTS1
      gene. LOH was found with at least 1 marker in 38% of the 201 cases analyzed. A
      high frequency of deletions was detected at the 9p23-p21 region, indicating a
      tumor suppressor gene(s) important for breast cancer tumorigenesis. Tumors with
      and without LOH on 9p were compared with respect to clinico-pathological factors
      using chi 2 analysis. Tumors with 9p LOH were significantly associated with high
      S-phase status and aneuploidy, but not with type, node status, estrogen and
      progesterone receptor content or age of the patients at diagnosis. Survival
      analysis showed that LOH at 9p did not significantly affect the survival rate of
      breast cancer patients. Our results indicate that the aberrations on 9p detected
      in this study are not of independent prognostic value. A significant association
      was found between LOH at 9p and LOH at chromosomal arms 3p and 6q, which is an
      additional contribution toward understanding the genetic events in breast tumor
      pathogenesis.

PMID- 8550239
TI  - Incidence of germ-line p53 mutations in patients with gliomas.
AB  - Epidemiological studies on intracranial tumors have suggested that the observed
      familial aggregation of a proportion of gliomas may be due to inherited
      predisposition to their development. In the Li-Fraumeni syndrome (LFS) associated
      with germ-line mutations of the p53 gene, nervous-system tumors are observed with
      increased frequency. However, the contribution of germ-line p53 mutation to the
      incidence of brain tumors has not been investigated. In order to address this
      point, we have performed 2 independent investigations. First, we have examined an
      unselected series of brain tumors. Whenever the presence of a p53 mutation in the
      tumor was observed, the possible germ-line origin of the mutation was
      investigated. Germ-line p53 mutations were also analyzed in constitutional DNA of
      patients with gliomas that had been selected for an unusual personal or familial
      history of cancer. Germ-line p53 mutations were detected in 1 out of 80
      unselected cases and in 3 out of 15 selected cases (20%). We conclude that germ
      line p53 mutation may contribute to a small fraction of gliomas that develop in
      the general population. The presence of a personal or familial history of cancer
      in a patient with glioma should prompt the search for a germ-line p53 mutation.
      However, the low frequency of p53 germ-line mutation suggests that alterations of
      this gene may not account for most familial cases of gliomas.

PMID- 8550240
TI  - Expression of MAGE-1, MAGE-2, MAGE-3/-6 and MAGE-4a/-4b genes in ovarian tumors.
AB  - MAGE genes encoding tumor-rejection antigens recognized by cytotoxic T
      lymphocytes are expressed at the mRNA level in various malignant tumors. We have
      investigated the expression of genes MAGE-1, -2, -3/-6 and -4a/-4b at the mRNA
      level in malignant and non-malignant ovarian tumors as well as in normal ovaries
      by reverse transcription-polymerase chain reaction. MAGE-1, -2, -3/-6 and -4a/-4b
      were expressed in 12, 5, 11 and 4 of 58 malignant tumors, respectively. The
      majority of these MAGE-mRNA-positive tumors were histologically surface
      epithelial-stromal tumors, in particular serous adenocarcinomas. They mostly
      consisted of either advanced-stage or recurrent tumors. In contrast, neither
      benign tumors nor normal ovaries expressed any of the MAGE genes investigated. A
      46-kDa MAGE-1 protein was identified in MAGE-1-mRNA-positive serous
      adenocarcinomas by immunoblot analysis with polyclonal anti-MAGE-1 antibody.
      These results provide important information for specific immunotherapy of ovarian
      serous adenocarcinomas with MAGE gene products.

PMID- 8550241
TI  - Risk modifiers in carriers of BRCA1 mutations.
AB  - The majority of, but not all, women with mutations in the BRCA1 gene will be
      affected with breast or ovarian cancer by the age of 70. To establish whether
      known risk factors modify susceptibility to cancer in these women, we have
      studied the reproductive histories of 333 North American women who were found by
      haplotype analysis to carry BRCA1 mutations. An increased risk for breast cancer
      was associated with low parity and with recent birth cohort. The risk of ovarian
      cancer decreased with increasing age at last childbirth; however, in contrast to
      the case for sporadic cancer, the risk of ovarian cancer in BRCA1 carriers was
      found to increase significantly with increasing parity.

PMID- 8550242
TI  - Detection of p53 gene alteration in renal-cell cancer by micropreparation
      techniques of tumor specimens.
AB  - Alterations in the p53 tumor-suppressor gene have been identified in a variety of
      human malignancies, including renal-cell cancer. A technique for the isolation of
      tumor areas from tissue specimens to analyze formalin-fixed and paraffin-embedded
      tumors and try to avoid a disturbance of the results due to genetic background
      signal by the presence of tumor-infiltrating lymphocytes, was established. The
      presence of lymphocytes within the tumor areas investigated was determined by
      immunohistochemical staining for CD3, a lymphatic surface antigen. Following the
      isolation of about 100-200 tumor cells, PCR-directed molecular genetic analysis
      was performed. A highly informative allelotyping approach for the detection of
      loss of heterozygosity (LOH), determining BstU1- and VNTR-polymorphisms, a 100-bp
      marker directly localized in intron 1 of the p53 gene, as well as screening for
      mutations by single-strand conformation polymorphism analysis (SSCP) in exons 5
      8, were used. Out of 44 renal-cancer specimens, 33 (75%) were informative for PCR
      directed RFLP-analysis. Allelic loss at the p53 gene locus was observed in 10 of
      33 cases (33%). No correlation between p53 gene alteration and T-stage,
      histological grade or histological differentiation could be observed. Alterations
      in the p53 gene, as detected by a molecular genetic as well as an
      immunohistochemical approach, were correlated to overall survival. During
      univariate analysis histological grade, lymphnode status and the presence of
      distant metastases could be identified as prognostic parameters for overall
      survival. During multivariate analysis none of the factors investigated remained
      an independent prognosticator for survival. Summarizing these results, it seems
      unlikely that p53 gene alterations will serve as an important new factor for the
      clinical prognosis of patients with renal-cell cancer.

PMID- 8550243
TI  - Expression of E- and N-cadherin in renal cell carcinomas, in renal cell carcinoma
      cell lines in vitro and in their xenografts.
AB  - E- and N-cadherins are proteins involved in intercellular adhesion and are
      localized, e.g., in the adherens junctions of epithelial cells. Kidney tubules
      express these molecules in a distinctive pattern, the expression of N-cadherin
      being restricted to proximal tubules and that of E-cadherin to distal tubules and
      collecting ducts. Renal cell carcinomas (RCCs) and oncocytomas are considered to
      originate from these tubular epithelia. To find out whether cadherins could serve
      as markers for a cellular origin of these tumors, we studied the expression of E-
      and N-cadherins in RCCs and oncocytomas, in cell lines derived from RCCs as well
      as in tumors grown in nude mice. Most RCCs co-expressed E- and N-cadherins, as
      did 2 of the 4 cell lines studied. The expression pattern did not correlate with
      the histological grade of the tumors, and even the least differentiated tumors,
      as well as metastases, showed expression of cadherins. Renal oncocytomas
      expressed E-cadherin but not N-cadherin, which is in line with previous studies
      that have proposed a collecting duct origin for these tumors. Papillary renal
      neoplasms, a separate entity usually not classified as RCC, expressed neither of
      the cadherins studied despite the abundant expression of beta-catenin. Our
      results suggest that most RCCs co-express the characteristic adhesion molecules
      of both proximal and distal tubules, which makes it questionable whether the
      origin of these tumors can be reliably located to any distinct part of the renal
      tubule. Our results also suggest that in RCCs the increased histological grade is
      not directly associated with changes in the expression of either of the
      cadherins, indicating other mechanisms underlying the deficient capacity to form
      polarized tubular structures.

PMID- 8550244
TI  - Expression of leukocyte cell adhesion molecules on gastric carcinomas: possible
      involvement of LFA-3 expression in the development of distant metastases.
AB  - Expression of the cell adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) was
      examined on primary gastric carcinomas, autologous benign mucosa and metastatic
      lesions. Although ICAM-1 was never observed on benign gastric epithelium, even in
      the presence of chronic inflammation and a strong leukocyte infiltrate, 38%
      (26/69) of the primary tumors expressed this molecule. ICAM-1 was restricted to
      differentiated tumors and correlated with the presence of leukocytes and the
      absence of vessel invasion. The ICAM-1 expression pattern of metastatic lesions
      reflected that of the primary tumor, suggesting that most tumors retain the non
      inducible phenotype seen in normal mucosa while some become cytokine-sensitive.
      ICAM-1 expression showed no correlation with tumor relapse or survival. LFA-3 was
      absent from 8% (4/49) of the primary tumors and reduced (e.g., < or = 50%
      positive cells) in 33% (16/49). Expression of LFA-3 by more than 50% of the tumor
      cells correlated with cellular dedifferentiation (G3, G4), histologically
      detectable vessel invasion, tumor recurrence and decreased survival time. Primary
      tumors and metastases in draining lymph nodes demonstrated a broad range of LFA-3
      expression. In contrast, distant metastases (liver and peritoneum) had uniformly
      high frequencies of LFA-3-positive cells, suggesting a selective advantage for
      these cells in the establishment of distant metastases.

PMID- 8550245
TI  - p53 protein accumulation and the presence of human papillomavirus DNA in
      bronchiolo-alveolar carcinoma correlate with poor prognosis.
AB  - Accumulation of the tumour suppressor gene p53 product due to a gene mutation is
      frequently seen in human carcinomas, including lung carcinoma. Another indirect
      mechanism involving p53 in malignant growth relates to the E6 protein of the
      human papillomavirus (HPV), which is able to bind and degrade wild-type p53
      protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar
      carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to
      examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC.
      Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM
      1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV
      types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty-six percent of the
      tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in
      situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs
      were positive for p53, whereas 45% of the type 2 BACs were positive. During a
      follow-up of 12-176 months, only 10% of the patients with BACs negative for both
      p53 and HPV died of the disease, compared with 42% of the patients with either
      p53 or HPV positivity. No inverse relationship between abnormal p53 protein
      accumulation and the presence of HPV DNA was found.

PMID- 8550246
TI  - Life-time risk of different cancers in hereditary non-polyposis colorectal cancer
      (HNPCC) syndrome.
AB  - Identification of hereditary non-polyposis colorectal cancer (HNPCC) indicates
      theoretical life-time risks of 50% for the descendants of an affected family
      member and of 100% for the true gene carriers. However, besides colorectal cancer
      (CRC), many other cancer types and sites are also involved, which gives reason to
      evaluate the magnitude of risk for various other cancer types. A detailed
      pedigree analysis of 40 families with HNPCC identified 414 patients affected with
      cancer. A Kaplan-Meier life-table analysis for the cumulative risk of various
      cancers was performed on the basis of the 293 putative gene carriers who had
      adequate clinical and histological documentation of their tumors. Cumulative
      risks were highest for colorectal (78%) and endometrial cancers (43%, women
      only), followed by gastric, biliary tract, urinary tract and ovarian cancers (19
      9%). For the other probably HNPCC-related cancer types, such as small bowel
      carcinoma and brain tumors, the life-time risk was only 1%. The risk of any
      metachronous cancer reached 90% after treatment of CRC and 75% after endometrial
      cancer; the second tumor was most often a new CRC or endometrial cancer. CRC
      remains the most important cancer type in the HNPCC syndrome but does not develop
      in all gene carriers. This makes the decision of possible prophylactic colectomy
      for test-detected gene carriers difficult. Of the many other cancer types
      involved, at least endometrial cancer is common enough to necessitate a specific
      surveillance program.

PMID- 8550247
TI  - Genetic alterations distinguish different types of ovarian tumors.
AB  - Seventy-four sporadic ovarian tumors were studied for loss of heterozygosity
      (LOH) and microsatellite instability (MI) with 20 polymorphic markers on
      chromosome 17 and at least I marker on every other chromosome. Additionally,
      activation of the K-ras oncogene was examined through mutation analysis of codon
      12. A majority of the tumors analyzed were low grade and/or of the mucinous
      histologic type. A negative correlation between LOH on chromosome 17 and K-ras
      activation was observed, with the former alteration present in the majority of
      high grade serous and endometrioid tumors and the latter most commonly found in
      the mucinous and low malignant potential (LMP) tumors. In 60% of cases where LOH
      on chromosome 17 was present, it was observed at all informative markers,
      indicating chromosome loss. In these cases, frequent events of LOH were observed
      on the other chromosomes. When confined events of LOH were observed on chromosome
      17, fewer events of LOH were observed on the other chromosomes. In the absence of
      LOH on chromosome 17, LOH on other chromosomes was rare. K-ras activation was
      most commonly observed in tumors with no LOH events. Two endometrioid tumors and
      2 mucinous tumors demonstrated MI. Our data support the involvement of different
      molecular pathways in the development of different types of ovarian tumors.

PMID- 8550248
TI  - The effect of oral coenzyme Q10 on the exercise tolerance of middle-aged,
      untrained men.
AB  - In order to determine the effect of oral Coenzyme Q10 (CoQ10) dosing on exercise
      capacity, 15 middle-aged men (44.7 +/- 2.0 years) received either CoQ10 (150
      mg/day x 2 months-Q10 GRP) or placebo (2 months-CON GRP). Blood CoQ10 levels
      increased (p < 0.05) during the treatment in the Q10 GRP (Pre = 0.72 +/- 0.06, 2
      months = 1.08 +/- 0.14 micrograms/ml) and were unchanged in the CON GRP (Pre =
      0.91 +/- 0.05, 2 month = 0.69 +/- 0.05 microgram/ml). Similarly, the subjective
      perception of vigor (visual analog scale 1-10 where, 10 = very energetic, and 0 =
      very, very unenergetic) increased (p < 0.05) in the Q10 GRP (Pre = 5.73 +/- 0.35,
      2 month = 6.64 +/- 0.45). However, maximal oxygen consumption (VO2max Pre = 2.97
      +/- 0.18, 2 month = 3.05 +/- 0.15 l/min) and lactate threshold (LT Pre = 2.04 +/-
      0.12, 2 month = 2.08 +/- 0.12 l/min), as measured on the cycle ergometer, were
      unchanged as a result of the CoQ10 treatment, Neither forearm oxygen uptake, nor
      forearm blood flow was found to be affected by the CoQ10. Although lactate
      release during hand-grip testing tended to decrease in the Q10 GRP (Pre = 227 +/-
      49, 2 month = 168.3 +/- 40 mumole/min) this was not significant (p > 0.05). It
      can be concluded that short-term (2 months) oral dosing with CoQ10 increases
      circulating blood levels of CoQ10 and the subjective perceived level of vigor in
      middle-aged men. However, short-term dosing does not improve aerobic capacity or
      firearm exercise metabolism as measured in this investigation.

PMID- 8550249
TI  - Lactate exchange and removal abilities in sickle cell trait carriers during and
      after incremental exercise.
AB  - Arterial blood lactate concentrations and pH were measured on seven black male
      sickle cell trait (SCT) carriers before, during and after incremental exhaustive
      bicycle exercise (25 W increments per minute) and compared with those of six
      control individuals of the same ethnic origin having a similar physical fitness
      level. The object of the experiment was to determine if SCT has an effect on
      lactate kinetics. At volitional exhaustion which was reached at a comparable
      overall mean absolute work rate for both groups, oxygen consumption expressed per
      kilogram body mass was significantly lower for the SCT carriers than for the
      control volunteers. Lactate concentrations were higher for the SCT carriers after
      the 150 W exercise step but differences reached statistical significance only at
      exhaustion. Concentrations were distinctly higher for the SCT group during the
      following 40 minutes of recovery. While there were no observable differences in
      blood pH between the SCT and control subjects during the exercise, this variable
      became significantly lower for the SCT than for the control group 8 minutes after
      the end of exercise. Lactate recovery curves were fitted by a biexponential time
      function where the two velocity constants inform on the body's overall ability to
      exchange and remove lactate. The ability to remove lactate was comparable for the
      two groups. The present results do not warrant drawing a definite conclusion on
      impairment of the ability to exchange lactate in the presence of SCT. However,
      SCT carriers are likely to produce more lactate than control subjects reaching
      exhaustion at similar mean absolute work rate during exhaustive incremental
      bicycle exercise.

PMID- 8550250
TI  - Dietary sodium intake and changes in plasma volume during short-term exercise
      training.
AB  - This study was a retrospective examination of the relationship between estimated
      dietary sodium intake and training-induced changes in plasma volume (PV). It was
      undertaken to explore one possible explanation for the large individual
      differences in PV shifts accompanying 3 d of endurance cycling. Ten healthy males
      rode a stationary cycle for an average time of 94 min/day at an average relative
      intensity of 68% VO2max. During the training period, the subjects were allowed to
      eat a diet of their own choosing and dietary sodium intake was estimated from
      diet records. Plasma volume was determined before and after short-term training
      by dye dilution using Evan's blue dye. The mean increase in PV was 4.53 ml.kg
      body weight (BW)-1 (i.e. 11%). However, the individual shifts in PV ranged from 
      1.44-14.30 ml.kg BW-1. The correlation coefficient between estimated dietary
      sodium intake and changes in PV was 0.81. It was concluded that dietary sodium
      intake was strongly associated with training-induced shifts in PV and may be an
      influential factor in determining the magnitude of PV expansion derived from
      short-term exercise training. Further studies are needed, however, to examine
      this hypothesis.

PMID- 8550251
TI  - The effect of beta-adrenergic blockade on non-esterified fatty acid uptake of
      exercising skeletal muscle during arm cranking.
AB  - beta-Adrenoceptor blocking agents impair endurance exercise performance in
      healthy subjects and in patients with hypertension. A possible explanation for
      the reduced exercise tolerance is a diminished availability of plasma non
      esterified fatty acids (NEFA) for energy production during exercise. This study
      investigated the effect of beta-adrenoceptor blockade on NEFA uptake of
      exercising skeletal muscle at elevated blood NEFA concentrations. In 11 healthy
      volunteers a triacylglycerol emulsion was infused at increasing rate for 1 hour
      before and 1 hour during one-armed cranking exercise at 60% Wpeak with and
      without prior administration of the beta 1+2-adrenoceptor blocking agent
      propranolol (80 mg per os). Arteriovenous concentration differences of NEFA
      across the active forearm were measured and forearm blood flow was estimated
      using venous occlusion plethysmography. Heart rate and blood flow were
      significantly lower after propranolol (p < 0.05). Propranolol did not affect
      arterial NEFA concentration, arteriovenous NEFA difference or NEFA flux
      significantly. Net NEFA uptake increased with increasing arterial NEFA
      concentration or inflow in a similar manner with and without prior propranolol
      administration. Therefore, the results do not support the hypothesis that beta
      adrenergic activity plays a role in the regulation of active skeletal muscle NEFA
      uptake under the conditions studied.

PMID- 8550252
TI  - Testosterone, growth hormone and IGF-I responses to acute and chronic resistive
      exercise in men aged 55-70 years.
AB  - We investigated the responses of serum testosterone (T) and human growth hormone
      (hGH) concentrations to a bout of heavy resistive exercise and the responses of
      T, hGH, and insulin-like growth factor I (IGF-I) to a 16 wk progressive resistive
      training program in 13 men (60 +/- 4 yrs). Body composition via hydrostatic
      weighing and muscle strength using a 3 repetition maximum (3RM) test on 6
      variable resistance exercise machines were assessed before and after the training
      program. Fasting blood samples were drawn on 2 consecutive days prior to training
      and again on 2 consecutive days after the last day of exercise. Blood was also
      drawn immediately before and approximately 10 min after a single exercise session
      during the first wk of training, and after an exercise session of the same
      relative resistance during the last wk of training. The training program resulted
      in a 37% increase in upper body strength and a 39% increase in lower body
      strength (both p < 0.01). Lean body mass increased significantly (61.8 +/- 2.1 vs
      63.7 +/- 7.8 kg; p < 0.001) while % fat decreased (26.5 +/- 1.5 vs 24.9 +/- 6.0%;
      p < 0.01) as a result of training. Serum T concentration was unchanged, but GH
      increased approximately 18-fold in response to a single bout of resistive
      exercise before (0.24 +/- 0.08 vs 4.60 +/- 1.35 mg/l) and after (0.26 +/- 0.06 vs
      4.66 +/- 1.46 mg/l; p < 0.01) training. Baseline serum concentrations of T, hGH,
      and IGF-I were unaffected by the training program. We conclude that an acute bout
      of resistive exercise causes a substantial hGH response in older men, but 16 wks
      of progressive resistive training does not affect baseline concentrations of the
      anabolic hormones.

PMID- 8550253
TI  - Differences in anaerobic performance between boys and men.
AB  - The purpose of this study was to compare the anaerobic performance of 11-12 year
      old prepubescent boys (stage 1; n = 18) using a maximal effort 90 s cycling test
      to that of adult men (n = 19). Performance was separated into short-term
      anaerobic power (SAP; work in 10 s), intermediate-term anaerobic capacity (IAC;
      work in 30 s) and long-term anaerobic capacity (LAC; work in 90 s). Resistance on
      the Monark cycle ergometer was chosen as the highest tolerable load for the 90 s
      test and set at 2.6 and 3.8 J. rev-1.kg body mass-1 for boys and men,
      respectively. Power drop-off (%PD) was determined as the change in 5 s power
      outputs from 0-90 s. Blood lactates were measured at rest (pretest; BL) and at 2
      (BL2) and 5 (BL5) min post test. Absolute and relative (to weight or thigh
      volume) scores for SAC, IAC and LAC were 33-40% lower in the boys compared to the
      men (p < 0.001). The men demonstrated significantly greater %PD over the 90 s
      (32.2%) compared to the 25.3% PD of the boys (p < 0.001), suggesting that the
      development of fatigue was greater in the men even though power and work outputs
      were high. Resting BL values were similar for both groups. Mean BL2 and BL5 were
      higher (p < 0.01) in the men (13.5, SD = 3.4; 12.5, SD = 2.8 mmol.l-1) than in
      the boys (9.1, SD = 1.7; 8.3, SD = 1.6 mmol.l-1). The anaerobic performance of
      the boys compared to the men cannot be completely explained by the lower
      resistance setting used. Although the boys were 50% lighter than the men, their
      resistance was 70% of that used for the men. The results do not support the
      contention that children and adults have similar abilities in short term,
      exhaustive work when corrected for size. Prepubescent boys appear to be limited
      in their ability to perform short-term as well as intermediate and long term
      anaerobic exercise compared to adult males.

PMID- 8550254
TI  - Exogenous glucose oxidation during exercise in relation to the power output.
AB  - In order to study the influence of the power output on the oxidation rate of
      exogenous glucose and on the contribution of the various substrates to the energy
      demand, we combined the use of artificially enriched 13C-glucose with classical
      indirect calorimetry during uphill treadmill exercise. Six young male healthy
      subjects underwent three exercise bouts, in a randomized order and at least two
      weeks apart, at a low (45% VO2max, 1822 +/- 194 ml O2/min for 4 hours), moderate
      (60% VO2max, 2582 +/- 226 ml O2/min for 3 hours), and high intensity (75% VO2max,
      3036 +/- 287 ml O2/min for 2 hours). After 10 min of exercise, each subject
      ingested 100 g of artificially 13C-labelled glucose dissolved in 400 ml of water.
      Over the four hours of the exercise at 45% VO2max, the amount of exogenous
      glucose oxidized was 89.5 +/- 5.9 g from the 100 g ingested. In all exercise
      bouts, the oxidation of exogenous glucose already began during the first 30 min
      after ingestion and peaked at 120 min. The maximum oxidation rates averaged 0.64
      +/- 0.07, 0.75 +/- 0.04, and 0.63 +/- 0.08 g/min, and the mean amounts of
      exogenous glucose oxidized over the first two hours averaged 51.7 +/- 8.0, 61.5
      +/- 6.6 and 50.9 +/- 8.45 g, at 45, 60 and 75% VO2max respectively. The
      contribution of the oxidation of exogenous glucose to the total energy supply
      progressively decreased when the power output increased, from 19.6 to 12.2%. In
      the meantime, the contribution of total carbohydrates (exogenous+endogenous)
      progressively increased from 55.1 to 77.8% while the contribution of lipids
      decreased from 35.5 to 16.6%. In conclusion, exogenous glucose ingested during
      exercise is largely oxidized and strongly contributes to the energy supply. The
      oxidation rate first increases with the power output, but levels off or even
      decreases at high intensity exercise.

PMID- 8550255
TI  - Effects of carbohydrate supplementation on performance during 1 hour of high
      intensity exercise.
AB  - The effects of carbohydrate supplementation on high-intensity exercise
      performance were examined in 5 moderately-trained subjects (age = 28.4 +/- 1.5
      yr; ht = 171.0 +/- 4.3 cm; wt = 66.25 +/- 6.32 kg). High-intensity exercise tests
      (initiated at the power output (PO) associated with 90% VO2 peak [mean = 201 +/-
      21 watts] x 60 min, with drop-off in PO allowed over time) were completed under
      the following randomized double blind conditions: 1) pre-exercise glucose polymer
      (G)/placebo during exercise (G/P), 2) G pre-exercise and during exercise (G/G),
      and 3) placebo pre-exercise and during exercise (P/P). Subjects ingested 300 ml
      of a sweetened placebo or a similarly flavored 10% G solution, immediately prior
      to and every 15 min during exercise. No differences were observed in PO among the
      3 treatments until min 40-60 where PO was greater with G. This resulted in
      significantly greater total work (and less drop-off in PO) with G (G/P = 619 +/-
      234kJ [14.5% lower than the value associated with 201 watts maintained for 60 min
      (724kJ)], G/G = 599 +/- 235 kJ [17.3% lower than the value associated with 201
      watts maintained for 60 min]) compared with placebo (P/P = 560 +/- 198 kJ [22.7%
      drop-off in average PO]) (p < 0.05). VO2 followed a similar pattern with no
      difference in VO2 over min 0-40 and significantly higher VO2 in G/P and a trend
      for higher VO2 in G/G during min 40-60 compared to placebo. Results of the
      present study indicate that, compared to placebo, pre-exercise ingestion of G (30
      g in 10% solution) results in less drop-off in PO during 1 hour of high-intensity
      exercise performance, and that no further benefit is observed when the same
      amount of G is also ingested every 15 min during exercise.

PMID- 8550256
TI  - Strenuous exercise and immunological changes: a multiple-time-point analysis of
      leukocyte subsets, CD4/CD8 ratio, immunoglobulin production and NK cell response.
AB  - This study was designed to examine the impact of exhaustive endurance exercise on
      a number of immune parameters of physically fit male subjects (VO2max 66.5 +/-
      5.3 ml/min/kg) who performed treadmill exercise at 65% of their VO2max for 120
      min. Serial blood samples were taken before, during and after exercise and
      changes in leukocyte and lymphocyte subset concentrations; immunoglobulin
      production in vitro; and natural killer (NK) cell response were measured. The
      exercise regimen was found to induce the well-known phenomenon of leukocytosis
      which consisted primarily of a granulocytosis and lymphocytosis. Among the
      lymphocyte subsets, peripheral pan T cells (CD3+) as well as helper (CD4+) and
      suppressor (CD8+) T cells were found to be elevated. A relatively smaller
      increase in CD4+ than CD8+ cells resulted in depressed CD4/CD8 ratios throughout
      the exercise period. After exercise, T cells declined progressively and, 2 h post
      exercise, were less than 60% of their pre-exercise level. In contrast, the
      CD4/CD8 ratio demonstrated a progressive increase, thus representing a reversal
      in the pattern observed during exercise and a trend towards an elevated ratio
      during recovery. B cells (CD19+) were relatively unaffected by exercise, although
      IgM production by pokeweed mitogen-stimulated lymphocytes obtained from blood
      samples after 120 min of exercise was significantly depressed. NK cells were
      affected dramatically by exercise. Both CD16+ cell numbers and NK cytotoxicity
      were increased during exercise, followed by a persistent depression in the post
      exercise period. The strenuous exercise induced profound effect on NK cells as
      evidenced by a 40% depression of the NK cell count for as long as 7 days after
      the cessation of exercise. Our results provide direct kinetic evidence
      demonstrating that exhaustive exertion alters both lymphocyte distribution
      pattern and effector function, suggestive of possible exercise-induced immune
      compromise, particularly in the post-exercise recovery period.

PMID- 8550257
TI  - Aldosterone levels and cardiac hypertrophy in professional cyclists.
AB  - Aldosterone has been associated with the development of cardiac hypertrophy and a
      correlation has been found between levels of aldosterone and the degree of
      cardiac hypertrophy in hypertensive patients. Our study aimed to test the
      relation between physiologic cardiac hypertrophy and serum aldosterone in a group
      of highly trained cyclists. Determination of the left ventricular mass index
      (LVMI) was performed in a group of 40 professional cyclists by using Devereux's
      formula with correction for body surface area. After an overnight fast, blood
      samples were collected and serum aldosterone levels were measured using RIA. LVMI
      and serum aldosterone were intercorrelated using linear regression analysis.
      Twenty-three of the 40 cyclists (58%) presented an LVMI > 130 g.m-1 and the other
      17 subjects (42%) presented an LVMI < 130 g.m-1. Serum aldosterone levels did not
      correlate with LVMI in either of the groups (LVMI > 130 g.m-1, r = -0.089; LVMI <
      130 g.m-1, r = 0.146). The lack of correlation of this hypertrophy with serum
      aldosterone levels suggests that physiologic hypertrophy of the athlete's heart
      could be caused by a different stimulus to that seen in pathologic hypertrophy of
      hypertensives.

PMID- 8550258
TI  - Effleurage massage, muscle blood flow and long-term post-exercise strength
      recovery.
AB  - Manual massage is commonly assumed to enhance long term muscle recovery from
      intense exercise, partly due to its ability to speed healing via enhanced muscle
      blood flow. We tested these assumptions by daily (for four days) massaging the
      quadriceps muscles of one leg on subjects who had previously completed an intense
      bout of eccentric quadriceps work with both legs. Immediate post-exercise
      isometric and dynamic quadriceps peak torque measures had declined to
      approximately 60-70% of pre-exercise values in both legs. Peak torques for both
      the massage and control leg tended to slowly return toward pre-exercise values
      through the subsequent four days (96 hrs). There was no significant difference
      between the isometric and dynamic peak torques between massage and control legs
      up to 96 hours post-exercise. Leg blood flow was estimated by determining femoral
      artery and vein mean blood velocities via pulsed Doppler ultrasound velocimetry.
      Massage of the quadriceps muscles did not significantly elevate arterial or
      venous mean blood velocity above resting levels, while light quadriceps muscle
      contractions did. The perceived level of delayed onset muscle soreness tended to
      be reduced in the massaged leg 48-96 hours post-exercise. It was concluded that
      massage was not an effective treatment modality for enhancing long term
      restoration of post-exercise muscle strength and its use for this purpose in
      athletic settings should be questioned.

PMID- 8550259
TI  - Instrumented analysis of the pivot shift phenomenon after reconstruction of the
      anterior cruciate ligament.
AB  - The pivot shift was analysed using an electrogoniometer linkage (OSI, CA, USA) in
      27 patients 18 to 24 months after reconstruction of the anterior cruciate
      ligament (ACL). The static passive AP-displacement of the tibia was also measured
      by a laxity tester in 20 degrees of knee flexion with a load of 90N. All patients
      had a positive pivot shift on manual examination before surgery. At follow-up 18
      patients had normal subjective knee function according to the Lysholm score and
      18 patients had returned to their preinjury, competitive activity level. Only
      three patients had a positive pivot shift on manual testing. In contrast a pivot
      shift curve was registered with the electrogoniometer in 18/27 in the operated
      knee. Their mean maximum tibial translation in the operated knee during the pivot
      shift test was 8.1 +/- 4.3 mm. In 10 of these patients a pivot shift-like motion
      pattern was recorded also in the non-operated knee. Generally patients with
      passive sagittal A-P displacement difference of the tibia of > +2 mm in
      comparison to the non-operated knee also had positive instrumented pivot shift
      tests. In six control subjects without previous knee injury the electrogoniometer
      revealed no pivot shift curve and the mean maximum sagittal translation was only
      3.4 +/- 1.3 mm. It seems that pathologic knee motions can be provoked manually in
      many patients two years after reconstruction of the ACL in spite of a generally
      good clinical result. In some patients also the non-operated knee shows a
      pathologic motion pattern that could not be demonstrated in normal subjects.
      Computerized registration of the pivot shift phenomenon was more sensitive than
      ordinary manual testing. These findings are in line with results previously found
      in vitro.

PMID- 8550260
TI  - Epidemiology for prevention.
AB  - This paper illustrates the basis of, expectations for and evaluation of
      prevention from an epidemiological perspective. Specifically, the extent to which
      epidemiologists could and should be involved in designing and evaluating public
      health interventions is addressed. Changes in the view on disease causation and
      epidemiology's role for the future of public health are discussed. Examples from
      cardiovascular epidemiology are used to illustrate the ever more complex, but
      still incomplete, knowledge on which prevention is based. A few current examples
      illustrate paradoxes where health information must balance academic discord.
      Methodological problems in the evaluation of intervention studies often fail to
      live up to the expectations of prevention. Outcome indicators of preventive
      projects must be developed and traditional appraisals of effects be supplemented
      with process analyses using both quantitative and qualitative methods. Social
      conditions for prevention are discussed and areas for further research are
      suggested.

PMID- 8550261
TI  - Body iron stores and mortality due to cancer and ischaemic heart disease: a 17
      year follow-up study of elderly men and women.
AB  - BACKGROUND: Increased body iron stores have been suggested as a risk factor for
      cancer and ischaemic heart disease (IHD). However, all studies carried out to
      date have focused on relatively young populations although the elderly may also
      be at increased risk. METHODS: We investigated the association between body iron
      stores and mortality due to cancer and IHD in a 17-year follow-up study of 260
      non-institutionalized elderly people aged 64-87 years. Iron status was assessed
      in 1971 by means of the haemoglobin level, transferrin saturation and total iron
      binding capacity (TIBC). Information about the vital status and causes of death
      was obtained in 1988. RESULTS: Among women mortality due to cancer was inversely
      related to TIBC; the relative risk for the highest tertile of TIBC, adjusted for
      age, smoking and alcohol intake was 0.05 (95% confidence interval (CI): 0.007
      0.39). The risk of mortality due to all-causes was also inversely associated with
      TIBC. Among men, no association between body iron stores and mortality due to
      cancer was observed. Mortality due to IHD was not clearly associated with body
      iron status. Among men, the adjusted relative risk decreased slightly per tertile
      of transferrin saturation, but this trend was only of borderline significance (P
      = 0.10). CONCLUSIONS: These results suggest that body iron stores are a risk
      factor for mortality due to cancer in postmenopausal women. This may be due to
      accumulation of stored iron among women after menopause. No clear associations
      with mortality due to IHD were observed in either elderly men or elderly women.

PMID- 8550262
TI  - Analysis of cancer rates using excess risk age-period-cohort models.
AB  - BACKGROUND: Recently the age-period-cohort (APC) model has become a popular
      epidemiological tool. However, it is well known that the model suffers from the
      identifiability problem. The simple multiplicative formulation of the model in
      terms of the age, period, and cohort variables without resorting to the
      underlying biology also casts doubt on the interpretability of the model
      parameters. METHODS: Excess risk APC models for cancers are developed based on
      carcinogenesis processes in human populations. These models have the beneficial
      feature of biological plausibility and do not suffer from the identifiability
      problem. Apart from the age, period, and cohort effects, a new kind of effect,
      the impact effect, is also introduced into the models. A computer program has
      been developed to fit the models which contain non-linear as well as restricted
      parameters. RESULTS: Two published mortality datasets are used to demonstrate the
      methodology. The proposed models fit better than the conventional APC model in
      both examples. CONCLUSIONS: Despite all the merits of the proposed models,
      several statistical issues should be investigated further before accepting this
      methodology as a general data-analytical tool.

PMID- 8550263
TI  - Coronary heart disease mortality in Australia: is mortality starting to increase
      among young men?
AB  - BACKGROUND: There has been a major decline in mortality from coronary heart
      disease (CHD) in Australia from about 1967 through to 1989, occurring across all
      age groups simultaneously. We have analysed data up until 1992 to examine for
      trends within age cohorts. METHODS: Death registrations for acute myocardial
      infarction and CHD were used to construct male and female 5-year age- and cohort
      specific mortality rates starting at 1900-1904 for cohorts and 25-29 years for
      age. Trends within age group and within cohort were compared across time.
      RESULTS: Across all female and most male birth cohorts there was a decrease in
      CHD mortality across the time period. In the youngest male cohorts there was a
      significant flattening in the rate of decline in the most recent periods.
      Comparison of age-specific mortality across cohorts showed the mortality at any
      period to be lower in the most recent cohort. CONCLUSIONS: This analysis
      demonstrates a continuing decline in mortality from CHD among females of all ages
      in Australia although the rate of decline appears to have slowed or even ceased
      in younger males.

PMID- 8550264
TI  - Ability of the Atherosclerosis Risk in Communities (ARIC)/Baecke Questionnaire to
      assess leisure-time physical activity.
AB  - BACKGROUND: The Atherosclerosis Risk in Communities (ARIC)/Baecke Questionnaire
      is a general survey of both occupational and leisure (sport and exercise related
      and non-sport and exercise related) physical activity. METHODS: Its ability to
      assess leisure physical activity was studied in 78 men and women, age 20-59
      years, by comparison to: six 48-hour physical activity records; 14 48-hour
      Caltrac accelerometer readings (Caltrac); three peak oxygen consumption (VO2
      peak) determinations; and per cent body fat. These criteria measures were
      obtained over a year's duration. RESULTS: The following associations were evident
      in men and women respectively, between sport and exercise physical activity and:
      physical activity record heavy intensity activity (r = 0.73 and r = 0.63); VO2
      peak (r = 0.67 and r = 0.45); and per cent body fat (r = -0.37, P = 0.08 and r = 
      0.44). Less concordance was evident (r = 0.39 for men and r = 0.23, NS, for
      women) between non-sport and exercise physical activity and physical activity
      record light intensity activity. Questionnaire and physical activity record
      indices of total leisure activity tended to be more closely related in men (r =
      0.59) than women (r = 0.33). For both men and women, survey results were not
      closely associated with Caltrac readings. CONCLUSIONS: Although there are
      weaknesses, questionnaire strengths consistent for both men and women include:
      ease of administration, high reliability, and accurate assessment of heavy
      intensity activity as well as light intensity activities such as walking and
      bicycling.

PMID- 8550265
TI  - Weight change and risk of heart attack in middle-aged British men.
AB  - BACKGROUND: Both weight gain and weight loss have been associated with increased
      risk of cardiovascular disease mortality in recent studies from the US. This
      finding has led to concern and uncertainty about appropriate advice for
      overweight and obese subjects. METHODS: In a prospective study of cardiovascular
      disease, the relationship between weight change over a 5-year period and
      subsequent risk of a heart attack during a further 6.5 year follow-up was
      examined in 7100 middle-aged British men. RESULTS: Over half of the men remained
      stable (< 4% change in bodyweight) and served as the reference group; 31% gained
      weight and 13% lost weight. The 6445 men free from a history of coronary heart
      disease experienced 318 heart attacks, fatal and non-fatal, during the 6.5 years.
      Men who gained 4-10% bodyweight had the lowest rate of heart attack, although
      this was not significantly different from the stable group. The men who lost
      weight had an increased risk of heart attack, which after adjustment (for age,
      recall of doctor-diagnosed hypertension and diabetes and other coronary risk
      factors i.e. serum total cholesterol, blood pressure, social class, initial body
      mass index (BMI) and lung function (FEV1), and smoking status at screening and 5
      years later), was of a similar level of risk to the stable group. The men who
      gained > 10% bodyweight had a significantly increased risk of a heart attack
      after the above adjustment (P < 0.05). When the effect of weight change was
      examined according to initial BMI, those men with a BMI < 25 kg/m2 who lost
      weight had a marginally increased relative risk of heart attack after full
      adjustment (P = 0.06), while men who were overweight (BMI 25-27.9 kg/m2) or obese
      (BMI > or = 28 kg/m2) showed no benefit from weight loss. A small amount of
      weight gain (4-10%) in the overweight or obese men was associated with decreased
      risk, whereas considerable weight gain (> 10%) was associated with increased
      risk, both findings reaching statistical significance in the overweight men (P <
      0.05 and P < 0.001 respectively). CONCLUSIONS: Considerable weight gain (> 10%)
      in middle-aged men is associated with increased risk of a heart attack, but
      weight loss does not appear to reduce risk even in the overweight or obese.

PMID- 8550266
TI  - Serum total homocysteine and coronary heart disease.
AB  - BACKGROUND: Several studies have observed high plasma levels of homocysteine
      among patients with coronary heart disease (CHD). The only prospective study was
      based on US physicians, and concluded that homocysteine was associated with
      subsequent myocardial infarction (MI). However, the association was limited to
      those above a threshold level of homocysteine. METHODS: We conducted a nested
      case-control study among the 21,826 subjects, aged 12-61 years, who were surveyed
      in the municipality of Tromso, Norway. Among those free from MI at the screening,
      123 later developed CHD. Four controls were selected for each case. RESULTS:
      Level of homocysteine was higher in cases than in controls (12.7 +/- 4.7 versus
      11.3 +/- 3.7 mumol/l (mean +/- SD); P = 0.002). The relative risk for a 4 mumol/l
      increase in serum homocysteine was 1.41 (95% confidence interval (CI): 1.16
      1.71). Adjusting for possible confounders reduced the relative risk to 1.32 (95%
      CI: 1.05-1.65). There was no threshold level above which serum homocysteine is
      associated with CHD events. CONCLUSIONS: In the general population serum total
      homocysteine is an independent risk factor for CHD with no threshold level.

PMID- 8550267
TI  - Maternal smoking during childhood and increased risk of smoking in young
      adulthood.
AB  - BACKGROUND: Effective prevention of smoking depends on the identification of
      factors that determine smoking onset. We examined the influence of family factors
      during childhood (household income, parents' education and smoking behaviour) on
      the subsequent risk of smoking in young adults. METHODS: In 1979, 1300 children
      aged 6-18 years, whose parents were randomly selected for participation in the
      Copenhagen City Heart Study were invited to a health examination. Information
      about health and smoking behaviour was obtained from 73% of the children. A
      random sample of 579 of the children were invited to a follow-up examination 13
      years later. In all, 486 (84%) participated in the follow-up. RESULTS: The
      influence of household income, parents' smoking behaviour and education on the
      child's risk of becoming a smoker in young adulthood was estimated. Household
      income and parents' education did not significantly affect the risk of adult
      smoking. Maternal smoking during childhood increased the risk in comparison with
      the mother being a non-smoker (adjusted odds ratio = 1.95; 95% confidence
      interval: 1.07-3.58). CONCLUSION: Maternal smoking during childhood increases
      children's risk of becoming young adult smokers, independent of age and smoking
      behaviour in childhood, gender and social background. In Denmark 28% of smoking
      in young adults could be attributed to maternal smoking.

PMID- 8550268
TI  - Exposure to environmental tobacco smoke and the risk of heart attack.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) increases the risk of heart disease
      in several epidemiological studies although the methods of assessing exposure
      have been incomplete. We determined the prevalence of ETS from various sources,
      and examined the association between ETS and the risk of myocardial infarction.
      METHODS: A hospital-based case-control study of myocardial infarction was
      conducted from 1980 to 1990 by interviewing 114 case patients and 158 control
      subjects. RESULTS: Among controls, the sources of ETS were the workplace (56%),
      childhood exposure (66%), home adult exposure (48%), car exposure (20%) and from
      trains or other surface transportation (4%). Compared to never smokers, the odds
      ratio (OR) for exposure to ETS during childhood was 0.97 (95% confidence
      intervals [Cl]: 0.53-1.46) for men and 0.92 (95% Cl: 0.5-1.86) for women. The
      adjusted OR associated with adult exposure was 1.5 (95% Cl: 0.9-2.6), although no
      trend was observed with the number of years of exposure. Women who were exposed
      to ETS in automobiles had an increased but non-significant risk (OR = 2.8, 95%
      Cl: 0.9-8.0). CONCLUSION: Exposure to ETS comes from a variety of sources besides
      the spouse including parents, workplace employees and motorists. Exposure to ETS
      during childhood is not associated with an increased risk of heart disease.
      However, ETS exposure during adulthood increased the risk of myocardial
      infarction approximately 50% in this data although the findings were not
      statistically significant.

PMID- 8550269
TI  - The sex ratio of mortality and its secular trends.
AB  - BACKGROUND: The mortality level from all causes is different between populations
      and it has decreased for both men and women in most countries in the last
      decades. However, there is a difference in the male/female sex ratio of mortality
      between populations and its time trends and the reasons for these differences
      remain unclear. METHODS: The sex ratio of all-cause mortality and the main causes
      of death, i.e. total cardiovascular disease and cancer, for 30 populations in
      1988 (mean of 1987-1989), and the time trends of the sex ratio for 27 populations
      are analysed. RESULTS: Large differences in the sex ratio of mortality exist
      among the studied populations. The sex ratio of all-cause, total cardiovascular
      and cancer mortality markedly increased in most countries during recent decades.
      CONCLUSIONS: The sex ratio of all-cause mortality and its time trends correlated
      significantly and positively with the sex ratio of mortality and its time trends
      from total cardiovascular disease and cancer. The differences of the sex ratio of
      mortality and their time trends between populations cannot be explained by
      genetic factors. They could be attributed to differences in life style. A
      different exposure and different reaction to the risk factors of cardiovascular
      diseases and cancer, e.g. saturated fat intake, alcohol intake and smoking
      habits, between men and women are considered to be the main causes for these
      differences in the sex ratio of mortality.

PMID- 8550270
TI  - Mortality in two Jewish populations--Montreal and Israel: environmental
      determinants of differences.
AB  - BACKGROUND: Mortality was compared in the Jewish populations of Montreal and
      Israel and the overall Canadian population, to investigate whether the Israeli
      pattern of low male mortality and relatively high female mortality is replicated
      among Jews living elsewhere. METHODS: In Montreal, death certificates were
      obtained from Jewish funeral homes (where all Jewish deaths are believed to be
      handled) for 1986-1990 and coded. RESULTS: All-cause cumulative mortality for
      ages 35-74 (CM), was exceedingly low in Montreal Jews, both in males (CM = 0.312,
      95% confidence interval [CI]: 0.274-0.350) and females (CM = 0.202, 95% CI: 0.172
      0.232), compared to all Canadians (CM = 0.425; 95% CI: 0.414-0.435 and 0.251; 95%
      CI: 0.243-0.253) and Israeli Jews (CM = 0.406; 95% CI: 0.379-0.434, and 0.299;
      95% CI: 0.276-0.322), for males and females. Sex ratios (male:female) were 1.36,
      1.54, and 1.69 for Israeli Jews, Montreal Jews, and Canadians, respectively.
      Differences were due mainly to substantially lower cumulative mortality from
      circulatory diseases in Montreal Jews (CM = 0.139, 0.043 versus 0.203, 0.125 in
      Israeli Jews and 0.199, 0.081 in Canadians, in males and females, respectively);
      these differences were all highly significant. Sex ratios for circulatory deaths
      were lowest in Israel (1.63), highest in Montreal (3.23) and intermediate in
      Canadians (2.47). Among men, the circulatory diseases mortality ratio for
      Canadians versus Montreal Jews was 1.43, and 1.46 between Israeli and Montreal
      Jews; in women, these ratios were 1.87 and 2.90, respectively. CONCLUSIONS: These
      findings suggest that the mortality pattern characteristic of Israeli Jews is not
      a universal Jewish phenomenon and may be affected by modifiable environmental
      factors. Similar studies conducted in other Jewish communities would aid in
      confirming these observations.

PMID- 8550272
TI  - Mortality study of construction workers in the UK.
AB  - BACKGROUND: Construction is one of the most dangerous industries in the world.
      However, there has been little literature on occupational epidemiology in this
      field. A study of the mortality experience over a 13-year period among
      construction workers in the UK was carried out. METHOD: This was based on 15,007
      death certificates of members of the Building and Civil Engineering Holiday and
      Benefit Scheme, who had died during 1975 to 1987 aged 20-64 years. Proportional
      mortality ratio (PMR) and mortality odds ratio techniques were used. RESULTS:
      Significantly elevated PMR were found for deaths from all cancers, including
      cancer of the lung and stomach, and for accidental deaths. Associations were
      demonstrated between several job categories and an increased risk of cancer
      mortality. Occupational exposures to hazardous substances may have contributed to
      the elevated cancer mortality, although the study findings should be interpreted
      with caution. Inadequate supervision of safety procedures, together with a high
      proportion of young and inexperienced workers, may be associated with the high
      number of accidental deaths. CONCLUSIONS: The results support the hypothesis that
      working in the construction industry is associated with a high risk for
      accidental death and probably also for malignant diseases including lung,
      mesothelium and stomach cancers. Further epidemiological studies among
      construction workers are needed to support policies aimed at improving
      occupational health, including the prevention of accidents.

PMID- 8550271
TI  - Causes of death contributing to urban socioeconomic mortality differences in
      Amsterdam.
AB  - BACKGROUND: Socioeconomic mortality differences exist between parts of many
      cities. This study aims to identify causes of death associated with such
      mortality differences and which preventive or curative interventions can modify.
      METHODS: Associations were compared between socioeconomic status and age
      standardized mortality by borough of Amsterdam, The Netherlands (n = 22) for
      causes of death grouped by feasible interventions. RESULTS: In men, mortality due
      to external and ill-defined causes occurs more frequently in low-income boroughs.
      In women, this holds for smoking-related and ill-defined causes. AIDS-related
      mortality is higher in boroughs with a high educational level. Mortality in low
      income boroughs is generally higher for those causes of death which explain the
      relatively high urban mortality. CONCLUSIONS: Interventions to decrease urban
      socioeconomic mortality differences should be targeted on violence and accidents
      in men and smoking in women. Incomplete notification of deaths in low-income
      boroughs obscures some differences but also indicates problems in urban general
      practice and specific risks for immigrant residents. AIDS reduces the size of
      mortality differences among men, probably temporarily. Both feasibility and type
      of interventions are relevant for many urban areas.

PMID- 8550273
TI  - Twin study using mortality data: a new sampling method.
AB  - BACKGROUND: To evaluate the success of a novel approach to twin studies using
      death discordant twin pairs in a disease of low prevalence. METHOD: A population
      study based on all registered deaths at the Office of Population Censuses and
      Surveys of England and Wales, classified under the ICD code 335.2 (motor neuron
      disease [MND]) for the period 1979-1989 inclusive. From the above database of
      10,872 people, individuals born after 31 December 1899 were traced in the Birth
      Indices for England & Wales to enable identification of possible twins. In all
      131 twin pairs were found and the co-twin details were sent to the National
      Health Service Central Register (NHS-CR) to enable location of the relevant
      Family Health Services Authority and thence the co-twin's general practitioner
      (GP). A letter requesting access was sent to the family practitioners. If given,
      the co-twin can be approached and interviewed. RESULTS: The search produced: 54
      living co-twins; 31 who died as adults; 29 infant deaths; 5 emigrated; 3
      incorrectly diagnosed index twins; and 9 untraceable co-twins. Among the adult
      deaths two concordant pairs were identified. This has created the largest twin
      population sample worldwide for MND. CONCLUSION: This new twin study method is
      clearly viable, and has produced a large unbiased sample compared to that
      possible using traditional methods. It relies heavily on the accuracy of death
      certificates and zygosity reporting by living co-twins, but is possibly the only
      way of collecting twins in rare conditions.

PMID- 8550274
TI  - Comparison of a quantitative dairy questionnaire with a dietary history in young
      adults.
AB  - BACKGROUND: There is growing interest in the potential role of calcium in the
      prevention of osteoporosis. Therefore a quantitative dairy questionnaire (DQ) was
      developed to estimate the calcium intake from dairy products. The aim of this
      study was to evaluate the relative validity and reproducibility of the DQ in 27
      29 year old males and females. METHODS: The DQ was validated against a cross
      check dietary history method (DH) in 160 subjects, and the reproducibility was
      assessed in 29 subjects by repeating the administration of the DQ with a one-year
      interval. RESULTS: In the validity study, the nutrient calcium and the food
      groups cheese and milk and milk products measured by the DQ tend to show higher
      intakes as compared to the results of the DH. However, only for the calcium
      intake was the difference between the DQ and DH (7%) significant. The Bland
      Altman plot showed that this bias was constant over the range of calcium intakes.
      The Pearson correlation coefficients between the DQ and the DH varied from 0.58
      to 0.65. On average, about 52% of the subjects were classified in the same
      quartile in the DQ and the DH for the intake of calcium as well as dairy
      products. The weighted kappas were between 0.60 and 0.67. In the reproducibility
      study, the Pearson correlation coefficient for the calcium intake assessed by the
      DQ one year apart was 0.78. CONCLUSIONS: These data indicate that the DQ is
      reasonably accurate in young adults as a means of assessing the calcium intake
      from dairy products.

PMID- 8550275
TI  - Diet and hip fracture risk: a case-control study. Study Group of the Multiple
      Risk Survey on Swedish Women for Eating Assessment.
AB  - BACKGROUND: The role of diet as a risk factor for osteoporotic fractures is
      unclear. Earlier studies have yielded conflicting results. METHODS: In two
      counties in central Sweden we investigated the association between dietary intake
      and the risk of proximal femoral fractures in a case-control study nested in a
      cohort. Women born in 1914-1948 were asked to fill out a food frequency
      questionnaire when invited to attend for mammographic screening between the years
      1987 and 1990. More than 65,000 women completed the questionnaire. Those who had
      participated in the enquiry and subsequently sustained a first hip fracture were
      defined as cases. For every case, four individually matched controls, by age and
      county of residence, were selected from the cohort. A second questionnaire
      concerning confounding factors was mailed to controls and cases. In all, 247
      cases and 893 controls could finally be included. Monthly intake of foods and
      daily intake of nutrients were calculated. RESULTS: When highest quartile of
      intake was compared to lowest, intakes of iron (adjusted odds ratio [OR] of 3.3,
      95% confidence interval [CI]: 1.6-6.9), magnesium (adjusted OR = 2.7, 95% CI: 1.3
      6.0) and vitamin C (adjusted OR = 1.9, 95% CI: 1.2-3.1) were found to be
      independent risk factors for hip fracture. High calcium intake did not protect
      against hip fracture. Smoking, low physical activity in leisure time, low body
      mass index, earlier fracture of the distal forearm and diabetes were all risk
      factors while postmenopausal hormone replacement therapy protected against hip
      fracture. DISCUSSION: This large study indicates new dietary risk factors for hip
      fracture. The association between high dietary intake of iron, magnesium and
      vitamin C and risk of hip fracture has not been reported previously. Further
      clinical and experimental studies are needed to confirm these findings and to
      investigate their mechanism of action.

PMID- 8550276
TI  - Body height and hip fracture: a cohort study of 90,000 women.
AB  - BACKGROUND: Hip fractures are a major public health problem. Recent studies have
      noted a connection between body height and hip fracture. METHODS: We investigated
      the relationship between body height and hip fracture using a prospective cohort
      of over 92,000 American, predominantly white, female nurses who were followed for
      10 years, from June 1980 to June 1990. The women, participants in the Nurses
      Health Study, were aged 35-59 in 1980. RESULTS: Women 5'8" or taller were more
      than twice as likely as women under 5'2" to sustain a hip fracture, after
      accounting for age, body mass index, cigarette smoking and alcohol consumption
      (multivariate relative risk 2.40, 95% confidence interval: 1.43-4.02; P for trend
      < 0.0001). CONCLUSION: Height appears to be an important independent risk factor
      for hip fracture among American women. Height should be included as a confounder
      in studies of hip fracture, and taller, elderly women should be advised to
      consider preventive measures.

PMID- 8550277
TI  - Incidence and progression of diabetic retinopathy among non-insulin-dependent
      diabetic subjects: a 4-year follow-up.
AB  - BACKGROUND: To assess the incidence and progression of diabetic retinopathy and
      explore risk factors associated with them among non-insulin-dependent diabetes
      mellitus (NIDDM) patients. METHODS: A total of 471 NIDDM subjects aged > or 40
      were recruited from four primary health care centres of northern Taiwan in 1986
      and followed up for 4 years. Their ocular fundi were clearly visible by
      ophthalmoscopy and the status of diabetic retinopathy could be graded. A
      structured questionnaire interview was conducted to collect basic data. Overnight
      fasting venous blood was collected every year to measure the levels of glucose,
      glycosylated haemoglobin (HbA1c), cholesterol and high density lipoprotein
      cholesterol. RESULTS: Among the 344 subjects who had no retinopathy initially, 66
      subjects developed retinopathy 4 years later giving a 4-year cumulative incidence
      of 19.2%. Of the 120 subjects initially with background or preproliferative
      retinopathy, evidence of deterioration developed in 36 subjects. The cumulative
      incidence of progression was 30%. Seven subjects developed proliferative
      retinopathy giving a cumulative incidence of progression to proliferative
      retinopathy of 5.8%. The univariate analysis disclosed that the development of
      retinopathy was correlated with mean fasting blood glucose (MFBG) and HbA1c,
      diabetic duration, diabetic treatment and residential area. The progression of
      retinopathy correlated with MFBG and proteinuria, and the progression to
      proliferative retinopathy correlated with MFBG. Stepwise logistic regression
      analysis revealed that MFBG and HbA1c were the significant risk factors related
      to the development of retinopathy. CONCLUSIONS: Diabetic control assessed by MFBG
      or HbA1c was the significant risk factor correlated with the incidence and
      progression of retinopathy.

PMID- 8550278
TI  - Facial skin symptoms in visual display terminal (VDT) workers. A case-referent
      study of personal, psychosocial, building- and VDT-related risk indicators.
AB  - BACKGROUND: The Office Illness Project in northern Sweden, comprising both a
      screening questionnaire study of 4943 office workers and a case-referent study of
      facial skin symptoms in 163 subjects was recently completed. Previously published
      results from the survey showed that female gender, asthma/rhinitis, high
      psychosocial work load, visual display terminal (VDT) and paperwork were related
      to an increased prevalence of facial skin symptoms. METHODS: The case-referent
      study presented in this paper used data from the questionnaire supplemented by
      information from a clinical examination, a survey of psychosocial factors at
      work, building data and VDT-related factors from inspection and measurements
      taken at the work site. RESULTS: Psychosocial conditions and exposure to
      electromagnetic fields or conditions associated with such factors were related to
      an increased occurrence of skin symptoms. The results also indicated that
      personal factors such as atopic dermatitis and physical exposure factors
      influencing indoor air quality, such as paper exposure and cleaning frequency
      were related to an increased prevalence of symptoms. CONCLUSIONS: The results
      suggest that skin symptoms reported by VDT users have a multifactorial
      background.

PMID- 8550279
TI  - Use of AIDS surveillance data to describe subepidemic dynamics.
AB  - BACKGROUND: Official reports on AIDS surveillance mainly consist of absolute
      numbers of AIDS cases or cumulative incidence rates. More detailed analyses
      focusing on the clusters of subepidemics within Italy seemed necessary for a
      better understanding and more accurate description of the epidemic. METHODS: Age
      specific AIDS incidence rates were calculated with reference to resident
      population by sex, calendar time and geographical area. Age-standardized
      incidence rates, with the Italian resident population in 1990 as standard, were
      used to present time trends and geographical distributions. All analyses were
      repeated for injecting drug users, homosexual/bisexual men, heterosexual contacts
      and individuals with other or undetermined risk factors. RESULTS: Annual
      incidence rates for AIDS in Italy increased over the study period. The highest
      rates were observed in the North and in Sardinia, while Southern regions showed
      generally lower rates. This heterogeneity was more evident when examining small
      geographical areas (i.e. provinces). Epidemics in some of the smaller provinces,
      such as Imperia and Livorno (Northwestern port towns), were shown to be important
      in that they greatly affect AIDS incidence rates in the regions in which they are
      located. CONCLUSIONS: According to our analysis, the crude presentation of data
      from the Italian AIDS Registry is not adequate for understanding the national
      spread of the AIDS epidemic in terms of several local subepidemics, which may
      differ by size, temporal trend, and risk group composition. Classifying cases
      according to their place of residence, which we considered as a good proxy of the
      place of life, was fundamental for correctly locating these subepidemics.
      Furthermore, the use of age-standardized rates allowed for unbiased comparisons
      between regions whose population may have a different age structure and dynamics.

PMID- 8550280
TI  - Impact on sexually transmitted disease spread of increased condom use by young
      females, 1987-1992.
AB  - BACKGROUND: Sexual behaviour data are crucial for understanding the spread of
      sexually transmitted diseases (STD). Over a period (1987-1992) in which the HIV
      epidemic increased public awareness of safe sexual practices, we describe
      predictors of condom use, changes in condom use over time, and the estimated
      effects of these changes on the spread of STD. METHODS: Condom use reported by
      females aged 18-35 years with non-cohabiting partners was analysed using data
      from two cross-sectional postal surveys performed 5 years apart (1987 and 1992)
      on two separate representative samples of 10,000 subjects aged 18-60 years living
      in Norway. A simple mathematical model was used to assess the effects of
      selection bias. A more complicated model was used to predict the effects of
      condom use on the prevalence of STD in a population which includes a core group
      of highly sexually active subjects. RESULTS: We found an increase in the
      prevalence of condom use in the latest intercourse from 14% to 20% with non
      foreign partners and from 10% to 38% with foreign partners, from 1987 to 1992. In
      a logistic regression model, low frequency of intercourse, high education, one
      lifetime partner, and late sexual debut were predictors for condom use.
      Controlled for these variables, the odds ratio (OR) for condom use in 1992 versus
      1987 was 1.4 (95% confidence interval [CI]: 0.9-2.0) if the partner was non
      foreign, and 7.1 (95% CI: 2.5-20.5) if the partner was foreign. Not using other
      contraceptive methods was a strong predictor for condom use; OR = 17.4 (95% CI:
      8.0-38.0). Condom use in the first intercourse with the last partner was a strong
      predictor for condom use in the last intercourse; OR = 19.2 (95% CI: 8.2-45.3).
      It appeared unlikely that the increase in condom use could be explained by
      response bias. The predicted reductions in STD prevalence due to the increase in
      condom use ranged from zero to 30% depending on consistency of use, and on the
      agent that is transmitted. CONCLUSIONS: Condom use among 18-35 year old women has
      increased over the period, particularly with foreign partners. Condoms are used
      primarily as contraception. The prevalences of STD with high transmission rates
      are not reduced by inconsistent condom use, while the prevalences of STD with low
      transmission rates are reduced by both consistent and inconsistent condom use.
      Condom use in a core group is more effective for reducing the STD prevalence than
      condom use in the non-core group for gonorrhoea and HIV. For chlamydial
      infection, condom use in the non-core group is more effective.

PMID- 8550281
TI  - An outbreak of hepatitis A among Irish haemophiliacs.
AB  - BACKGROUND: An outbreak of hepatitis A (HAV) occurred in 1992 in Irish
      haemophilia A patients treated with high purity solvent-detergent (SD) treated
      factor VIII. Similar outbreaks were reported in Italy, Germany and Belgium. The
      aim of this study was to investigate the outbreak, and to test the hypothesis
      that it was caused by exposure to SD-treated factor VIII. METHODS: A case-control
      study was started in early 1993. Haemophilia A cases with acute HAV (n = 29) were
      compared with haemophilia A controls for exposure to SD-treated factor VIII and
      other environmental factors. Details of factor VIII usage were obtained from the
      National Haemophilia Register and environmental data were obtained by a telephone
      administered questionnaire. The response rate was approximately 90%. RESULTS: The
      incidence of acute HAV infection among haemophilia A patients exceeded the
      notified national incidence of HAV by a factor of approximately 300. The
      incidence was higher in younger patients and those with more severe bleeding
      disorders. Contact with hepatitis, with children, and exposure to factor VIII
      were associated with increased risk. The association with factor VIII was the
      strongest risk factor after controlling for other factors (odds ratio = 27.6, 95%
      confidence interval [CI] 6.5-117.3). A dose-response effect was demonstrated.
      CONCLUSIONS: Although person-to-person transmission is likely to have caused a
      few of the cases, the results of our investigation suggest that the major
      contributing factor was exposure to certain batches of SD-treated factor VIII.

PMID- 8550282
TI  - Clusters of acute appendicitis: further evidence for an infectious aetiology.
AB  - BACKGROUND: The aetiology of appendicitis, the commonest cause of acute abdomen,
      is unknown. Infection has been proposed but the evidence has been unconvincing.
      The purpose of the present study was to investigate if temporo-spatial clustering
      and outbreaks, characteristics of infectious diseases, could be found in
      appendicitis cases in a defined Swedish population. METHODS: Temporo-spatial
      clustering among 1155 cases from three districts of Jonkoping County in 1984-1990
      was identified by Knox space-time cluster analysis. Outbreaks were identified by
      retrospective study of temporal variations in 3590 consecutive cases of acute
      appendicitis from the city of Jonkoping in 1969-1990. RESULTS: Space-time
      clustering was found among patients with operations less than 60 days apart
      (observed/expected [O/E]-ratio 1.46, P = 0.016). Subset analysis revealed
      clustering to be commonest among patients from the same households (O/E-ratio
      6.52, P = 0.012), among patients younger than 15 years (O/E-ratio 3.61, P =
      0.004) and among females (O/E-ratio 2.28, P = 0.004). Three outbreaks with a
      significantly increased number of cases were observed during the 22-year study
      period (O/E-ratio 1.6-2.2, P = 0.001-0.049). CONCLUSIONS: The finding of temporo
      spatial interaction and outbreaks among appendicitis cases supports the concept
      that appendicitis may be caused by infectious agents.

PMID- 8550283
TI  - Minimum attack rate for measuring measles vaccine efficacy.
AB  - BACKGROUND: For evaluating measles vaccine efficacy (VE) in the field, some
      investigators have suggested that an overall attack rate level of 5% or more in a
      randomly mixing population is sufficient to provide equal exposure to the viral
      agent in both vaccinated and unvaccinated groups. It is not clear, however, if
      this assumption is valid given the effect of herd immunity. METHODS: We created a
      computer simulation model based on the stochastic extension of the Reed-Frost
      model and tested for variation in bias in VE estimation due to herd immunity,
      based on runs of 200 trials. RESULTS: At higher levels of attack rate, the degree
      of herd immunity decreases, as does the percentage of trials with bias in VE
      estimation. The two main factors that affect the level of attack rate are the
      probability of adequate contact and the number of susceptibles. At a given level
      of attack rate, the number of susceptibles is positively associated with the
      percentage of biased trials in VE estimation. Since vaccination reduces the
      number of susceptibles, we also observe that when controlling for attack rate,
      higher vaccination coverage results in lower bias in VE estimation. CONCLUSION:
      The results show that the assumption of no bias when the attack rate is 5% or
      more becomes increasingly true when a large percentage of a randomly mixing
      population is immune.

PMID- 8550285
TI  - Exposure measurement errors, risk estimate and statistical power in case-control
      studies using dichotomous analysis of a continuous exposure variable.
AB  - BACKGROUND: Non-differential errors in exposure measurements have been shown to
      lead to differential misclassification of exposure. As a consequence, the common
      tenet that, in absence of bias, imprecise exposure assessment can only bias the
      risk estimates conservatively does not necessarily hold. We investigate the
      effects of exposure measurement errors on the risk estimate and on statistical
      power. METHODS: We used a computer model that simulates a case-control study. We
      used both hypothetical data and data modelled on empirical measurements of
      environmental magnetic fields exposure. RESULTS: Measurement errors are found to
      have a lesser impact on risk estimates and statistical power than would have been
      the case had misclassification been truly non-differential. However, for a given
      cutpoint, a bias away from the null cannot be excluded. The predominant direction
      of the errors is found to have important consequences on both the study power and
      the risk estimates. CONCLUSION: When sufficient empirical data are available,
      computer modelling may give a more accurate estimate of the effects of
      measurement errors than algebraic corrections.

PMID- 8550284
TI  - Assessing the efficacy of a mixed vaccination strategy against rubella in Sao
      Paulo, Brazil.
AB  - BACKGROUND: In 1992 a major vaccination strategy against measles-mumps-rubella
      was introduced in the State of Saao Paulo, Brazil. This strategy was based on
      mathematical models and comprised a pulse vaccination covering all children aged
      1-10 years, followed by the inclusion of this vaccine in the routine calendar at
      15 months of age. The present work reports the evaluation of the efficacy of this
      mixed vaccination strategy. METHODS: A rubella seroprevalence survey was carried
      out immediately and one year after the campaign, comprising 4953 children aged 1
      15 years. RESULTS: We show that average rubella seroprevalence increased from
      0.40 to 0.97 and that the reported number of congenital rubella syndrome (CRS)
      cases dropped dramatically. CONCLUSIONS: The mixed vaccination strategy adopted
      against rubella has proved to be very effective in reducing the number of CRS
      cases in Sao Paulo.

PMID- 8550286
TI  - Are mitochondria inherited paternally in Ascaris?
AB  - Mitochondrial DNA (mtDNA) is finding increasing usage as a tool for studying the
      systematics, population genetics and epidemiology of parasitic helminths, and is
      generally assumed to be inherited maternally. Yet two features of Ascaris biology
      -fertilization by large amoeboid sperm and some novel aspects of sperm
      mitochondria--suggest a paternal component to mitochondrial inheritance in this
      organism. In this study, we compare mtDNA restriction patterns of parental worms
      with those of their progeny but find no evidence for paternal inheritance. We
      suggest that sperm-derived mitochondria are actively destroyed or outcompeted by
      maternal organelles in the zygote.

PMID- 8550287
TI  - Endectocidal drugs: ecological risks and counter-measures.

PMID- 8550288
TI  - The life-cycle of the bont tick Amblyomma hebraeum in vitro.
AB  - The life-cycle of the hard tick Amblyomma hebraeum was completed in vitro by
      feeding all life-stages of the tick through silicone membranes on bovine blood
      from an abattoir. Ticks were placed in a simple feeder membranes on bovine blood
      from an abattoir. Ticks were placed in a simple feeder consisting of a honey jar
      containing the blood with a glass tube insert (o.d. 42 mm) across the end of
      which the membrane was stretched. This feeding unit was held in a water bath (38
      degrees C). Larvae and nymphs fed on a membrane (< 90 microns thick) made of
      silicone reinforced with Kodak lens cleaning paper, and adults on a silicone
      membrane (0.5 mm thick) reinforced with Terylene netting. To control microbial
      growth, gentamicin (5 micrograms/ml) and nystatin (100 i.u./ml) were added to the
      weekly open-collected blood, which was manually defibrinated. The blood was
      changed twice daily for nymphs and three times for adults and larvae. Attachment
      of ticks was induced with combinations of host hair, tick faeces, a bovine pelage
      extract and a synthetic aggregation-attachment pheromone mixture. The in vitro
      life-cycle started with unengorged "natural" adults, which had moulted from
      nymphs fed on steer. The life-cycle closed with unengorged, first in vitro
      generation adults which had moulted from nymphs fed in vitro. Although the
      feeding and development of larvae and nymphs were similar to in vivo controls,
      females fed and developed poorly in vitro. The toxicity of the systemic acaricide
      Ivermectin for nymphs of A. hebraeum was confirmed using the in vitro feeding
      method.

PMID- 8550289
TI  - The life cycle stages of three Diplostomum species maintained in the laboratory.
AB  - The taxonomy of Diplostomum species is in a highly confused state due to synonomy
      and descriptions based on only one life cycle stage. The objective of this study
      was to establish and maintain life cycles of several Diplostomum species in the
      laboratory so that accurate and detailed descriptions could be made.
      Metacercariae taken from the eyes of fresh water fish were identified using the
      key of Shigin (1986). Adopting the method of Field, McKeown & Irwin (1994) life
      cycles of Diplostomum spathaceum, Diplostomum parviventosum and Diplostomum
      volvens were established and each stage was described, measured and photographed
      or illustrated as required. The results of this work will provide standard
      descriptions for the life cycle stages of these Diplostomum species. It will
      relieve some of the identification difficulties experienced when only one stage
      in the life cycle is encountered.

PMID- 8550290
TI  - Migration route of Strongyloides venezuelensis in rodents.
AB  - Infective larvae of Strongyloides venezuelensis were injected into the medial
      aspect of the thigh of Wistar rats and ddy mice to investigate their distribution
      within their hosts with the passage of time. The parasite migrated subcutaneously
      or intramuscularly towards the upper body and gradually arrived in the lung from
      45 h post infection (p.i.) in rats and from 42 h p.i. in mice. After the larvae
      passed through the trachea, they first appeared in the small intestine at 60 h
      p.i., probably via the oesophagus and stomach. In comparison to the rats, more
      larvae were recovered from the mice at all times, and a higher concentration of
      larval localization was observed in the mice. The present study has established a
      good model of larval migration of S. venezuelensis in rodents, with the migration
      route apparently different from of Strongyloides ratti, another species found in
      rodents.

PMID- 8550291
TI  - Spermatogenesis in Octomacrum lanceatum (Monogenoidea, oligonchoinea,
      mazocraeidea).
AB  - Ultrastructural aspects of spermatozoon development and morphology in Octomacrum
      lanceatum are presented. Spermiogenesis involves development of zones of
      differentiation from the surface of cytophores followed by formation of a middle
      cytoplasmic process and 2 free flagella whose axonemes form from basal bodies
      located within each zone of differentiation. The mitochondrion and nucleus
      penetrate through the zone of differentiation into the middle cytoplasmic
      process. An intercentriolar body is present. Initially the axes of the basal
      bodies are perpendicular to that of the intercentriolar body but subsequently
      rotate about 90 degrees to parallel positions as the flagella develop. Flagella
      are initially free, but eventually fuse with the middle cytoplasmic process from
      the proximal to distal end (proximodistal fusion). Subsurface microtubules occur
      within the zone of differentiation but are lacking from the lateral regions of
      the middle cytoplasmic process. The mature sperm possesses two axonemes, one
      mitochondrion, and a complete ring of cortical microtubules (sperm pattern 1).
      The finding of sperm pattern 1 in the Octomacridae suggests that many features of
      the spermatozoon of the Diplozoidae are autapomorphic.

PMID- 8550292
TI  - Avermectins and milbemycins against Fasciola hepatica: in vivo drug efficacy and
      in vitro receptor binding.
AB  - Few studies have examined activity against trematodes for the
      avermectin/milbemycin class of anthelmintics. To gain insight into this, 12
      different members of the avermectin/milbemycin mode of action class were tested
      against juvenile Fasciola hepatica in a mouse model. The compounds chosen were
      Avermectin A1, Avermectin A2, Avermectin B1, Avermectin B2, Ivermectin,
      Ivermectin monosaccharide, Ivermectin aglycone, 13-deoxy ivermectin aglycone,
      Moxidectin, 13-O-methoxyethoxymethyl ivermectin aglycone, 4"-deoxy-4"-epi
      methylamino avermectin B1, and 4"-deoxy-4"-epi-acetylamino avermectin B1 5-oxime.
      Each of these compounds was administered orally to 4 mice at 2.0 mg kg-1. These
      mice had been administered 3 metacercariae of F. hepatica 14 days prior to
      treatment and all mice were necropsied 4 days after treatment. At necropsy, none
      of the individual avermectin or milbemycin-treated groups showed any significant
      activity (P > 0.05) against juvenile F. hepatica relative to a vehicle-treated
      control. In a receptor binding study, adult F. hepatica that had been obtained
      from sheep were homogenized, their membranes incubated in the presence of 3H
      ivermectin, and then measured for high affinity binding sites. The same was done
      with the free-living nematode, Caenorhabditis elegans. While the C. elegans
      membranes displayed high affinity 3H-ivermectin binding sites over the range of
      ivermectin concentrations tested (5-100 nM), no significant 3H-ivermectin binding
      sites were detected in the F. hepatica membranes. Based on these data, it seems
      unlikely that any avermectin or milbemycin will show activity against F.
      hepatica, and certainly makes one pessimistic about possible activity of this
      mode of action class against trematodes in general.

PMID- 8550293
TI  - An organelle-like small subunit ribosomal RNA gene from Babesia bovis: nucleotide
      sequence, secondary structure of the transcript and preliminary phylogenetic
      analysis.
AB  - Investigations aimed at identifying the mitochondrial genome of Babesia bovis
      using the polymerase chain reaction (PCR) have established the existence of an
      organelle-like small subunit ribosomal RNA (SSU rRNA) gene in the parasite. The
      sequence, compiled from three main PCR products, was 1448 bp in length (including
      the primer regions), had a 73% A+T content and showed significant similarity (68%
      sequence identity) to the "organellar" SSU rRNA gene from Plasmodium falciparum.
      The proposed secondary structure of the transcript showed several features which
      were consistent with a eubacterial origin for the organelle-like gene. The
      presence of putative binding sites for streptomycin and tetracycline also
      supported an "organellar" location for the gene and suggested that the SSU rRNA
      transcript is functional in protein synthesis because tetracycline has anti
      babesial activity. Phylogenetic analyses based on the conserved regions of the
      SSU-like rRNA genes from a wide variety of organisms showed only a weak
      association of the babesial sequence with its mitochondrial homologues and an
      even weaker association with the corresponding genes of plastid origin. The
      origin of this organelle-like gene in B. bovis therefore remains unresolved, as
      is the case for its homologue from P. falciparum.

PMID- 8550294
TI  - Expression of a 32 kilodalton Theileria sergenti piroplasm surface protein by
      recombinant baculoviruses.
AB  - Previous studies detected a single amino acid substitution (Ala196 to Gly196)
      between cDNA clones encoding a 32 kDa antigen (p32) of Theileria sergenti
      (Chitose stock) obtained from a persistently infected calf. In this study, 2
      different recombinant baculoviruses (pAc/p32-Ala196 and pAc/p32-Gly196) were
      constructed for the expression of p32. Molecular masses of the polypeptides
      produced in Spodoptera frugiperda cells infected with the recombinant
      baculoviruses were the same as that of authentic p32. pAc/p32-Ala196 produced
      additional polypeptides, with molecular masses higher than 32 kDa, which resulted
      from differential N-glycosylation as revealed by endo N-glycosidase treatment.
      The results indicate that a single amino acid substitution may lead to a
      conformational change in p32 which affected post-translational modification of
      recombinant products.

PMID- 8550295
TI  - Aspects of the ecology of metazoan ectoparasites of marine fishes.
AB  - Numerous (3947) individuals of 102 marine fish species from Papua New Guinea, New
      Zealand, the North Sea, Antarctica, the deepsea and coast of southeastern
      Australia, Pacific Canada, Brazil, Argentina and the Great Barrier Reef were
      examined for metazoan ectoparasites. Of the 102 fish species, 86 harboured at
      least 1 parasite species, and only in Antarctica and the deepsea were large
      proportions of fish species found to be free of ectoparasites. The mean
      prevalence of infection was 30.1%, the average of abundances was 6.7 parasites
      per fish, due to very heavy intensities of some parasite species (mean median
      abundance 4.31). Most parasite species exhibited a clustered distribution in the
      host populations, as measured by variance to mean ratios, i.e. some fish were
      more, and others less, heavily infected than if infection were random. Core and
      satellite species cannot be distinguished unambiguously, because numbers of
      parasites on almost all hosts are too small for any bimodality to become
      apparent. On average, the most dominant species represented 90% of all parasite
      individuals of a particular fish; different parasite species were often dominant
      on different fish individuals of a particular host species. Both abundances and
      maximum intensities of infection were positively correlated with prevalence of
      infection. Community richness varies greatly at and between localities, with the
      lowest richness found in Antarctic and deepsea fish and the highest richness in
      tropical fish. Species richness, abundance and prevalence of infection in many
      fish groups (with different ecological characteristics) are strongly correlated
      with temperature. If fish from all localities were pooled, pelagic fish had fewer
      intensities and (jointly with benthopelagic fishes) fewer species than benthic
      fish, and planktivorous fish had lower abundances and prevalences of infection
      than predatory and omnivorous fish. Prevalences of infection, abundance and
      parasite species richness were significantly correlated with host length. Fifteen
      positive and 1 negative associations among species were found. This and the
      generally low prevalences and abundances of infection indicate that competitive
      interactions are probably scarce. Overall, the findings indicate that most (if
      not all) metazoan ectoparasite communities of marine fish live in non-saturated,
      little-ordered assemblages.

PMID- 8550296
TI  - Serum antibody responses in opisthorchiasis.
AB  - We evaluated an enzyme-linked immunosorbent assay using crude parasite
      homogenates as a diagnostic test for Opisthorchis viverrini infection in humans.
      Serum antibody (Ab) responses to O. viverrini adult worm homogenate (AWH) and
      metacercaria homogenate (MH) were studied in 83 infected residents of an
      opisthorchiasis-endemic area in Thailand. Elevated levels of Ab persisted for
      over 1 year following curative treatment with praziquantel, and cross-reactivity
      to O. viverrini AWH and MH antigens was observed in sera from individuals with
      other parasitic infections. Serum Ab to crude AWH and MH are therefore unsuitable
      for immunodiagnosis since they may be non-specific and would not differentiate
      between ongoing and past infection.

PMID- 8550297
TI  - Immunotherapy with IL-2-stimulated splenocytes reduces in vitro the level of
      Leishmania donovani infection in peritoneal macrophages.
AB  - A study was done in vitro to determine if IL-2-stimulated lymphocytes (LAK cells)
      would activate infected macrophages to reduce their burden of Leishmania
      donovani. Macrophage-depleted splenocytes from normal or infected C57BL/6 (H-2b;
      LshS) mice, stimulated in vitro by the IL-2-containing supernatant of the MLA 144
      cell line or by rIL-2, significantly reduced the number of syngeneic resting
      peritoneal macrophages infected by L. donovani; LAK cells from infected animals
      were significantly more effective in reducing the numbers of infected cells.
      Supernatants of MLA 144-stimulated spleen cells and rIL-2-stimulated splenocytes
      isolated in Millipore chambers also induced a significant reduction of the
      infection in vitro. Anti-Thy 1.2 eliminated the ability of the supernatant of MLA
      144 to induce an activating function in C57BL/6 splenocytes; monoclonal anti-IL-2
      abolished the ability of rIL-2 and of the MLA 144 supernatant to stimulate the
      splenocytes. Infected resting peritoneal macrophages of C57L (H-2b; LshR) mice
      were more responsive to activation than those of the C57BL/6 animals,
      irrespective of the phenotype of the stimulating LAK cells. Lymphokine
      stimulation reverses the immunological anergy induced in T lymphocytes by
      Leishmania donovani; IL-2-stimulated LAK splenocytes are highly effective in
      reducing the intensity of experimental visceral leishmaniasis in vitro in
      peritoneal macrophages.

PMID- 8550298
TI  - Effect of ivermectin prophylaxis on antibody responses to Onchocerca volvulus
      recombinant antigens in experimentally infected chimpanzees.
AB  - Antibody responses to recombinant Onchocerca volvulus antigens were studied in
      experimentally infected chimpanzees. Sera from 3 groups of 6 animals were tested
      by ELISA with recombinant antigens OC 3.6 and OC 9.3. Groups I and II were
      treated with 200 micrograms/kg of ivermectin on the day of infection or on day
      28, respectively. Group III were untreated controls. Antibodies to OC 3.6
      developed during the prepatent period in all 3 groups. In contrast, antibodies to
      OC 9.3 were usually first detected around the time of onset of patency. Several
      animals had early antibody responses to OC 9.3, but these animals subsequently
      failed to develop microfilarial patency. Only 1 of 6 animals in group I produced
      a strong antibody response to OC 9.3 while all 12 animals in groups II and III
      developed antibodies to this antigen. Although there was some inconsistency in
      antibody responses observed in each treatment group, the results suggest that OC
      9.3 may be more useful than OC 3.6 for monitoring the efficacy of prophylactic
      drugs or vaccines for onchocerciasis while OC 3.6 may be useful for detecting
      exposure to the parasite and early infection, regardless of the later outcome of
      the infection.

PMID- 8550299
TI  - Oral and parenteral vaccination against Trichinella spiralis infections in high-
      and low-responder mice.
AB  - Vaccination by different routes and with different adjuvants is known to
      influence profiles of immune responses and may be used to overcome genetically
      determined low-responsiveness to infection. A mouse model of infection with the
      intestinal nematode Trichinella spiralis was used to investigate the effect of
      mode of vaccination upon immune responsiveness and worm expulsion phenotype in
      high- (NIH) and low- (C57 BL/10) responder strains of mice. Muscle larval
      homogenate antigen was given subcutaneously in Freund's complete adjuvant (FCA)
      to induce a systemic immune response or with cholera toxin (CT) orally to
      stimulate mucosal immunity. Both approaches significantly protected NIH mice.
      Vaccination with FCA was correlated with elevated serum IgG after infection,
      whereas oral CT-vaccination resulted in increased levels of intestinal IgA.
      Neither type of vaccination successfully protected the low-responder C57 BL/10
      strain and there were no effects on the low antibody levels that infection
      induced in this strain.

PMID- 8550300
TI  - Schistosome eggs in the portal vein can induce tolerance.
AB  - Schistosoma japonicum lives in the portal vein and/or mesenteric vein of
      patients, producing numerous eggs which eventually induce multiple granulomas in
      the liver and the intestine. The experimental administration of Schistosoma
      japonicum eggs via the portal vein in the mouse induces tolerance both in the
      footpad reaction and granuloma formation in the lung. Thus, the presence of
      Schistosoma japonicum in the portal vein is beneficial to the parasites, not only
      for receiving enriched nutrition from the blood of the portal vein, but also for
      inducing immunological tolerance in the hosts. However, prior intravenous
      injection of gadolinium chloride abolishes such tolerance, indicating the role of
      Kupffer cells in the induction of tolerance via the portal vein.

PMID- 8550301
TI  - The relationship of experimental pathogenicity in vivo with in vitro
      cytoadherence and cytotoxicity of 6 different isolates of Trichomonas vaginalis.
AB  - The experimental pathogenic effects in vivo and in vitro of 6 different isolates
      of Trichomonas vaginalis were studied following their inoculation into NMRI mice
      and on to adherent cultures of HeLa cells. Contact between the parasite and the
      adherent monolayer of cells was necessary to induce the monolayer to detach. The
      strains which were more virulent to mice also showed a greater weighted index of
      adherence; the weighted index of cytotoxicity in vitro did not, on the other
      hand, correlate with experimental pathology in vivo.

PMID- 8550302
TI  - Categorisation of the patient's medical condition--an analysis of nursing
      judgement.
AB  - This paper is a report of a study designed to explore the way in which community
      and hospital based nurses categorised 35 medical conditions. The results,
      obtained from a series of card-sorts using a Multiple Sorting Task and a modified
      Q-Sort, found that nurses used four global sub-categories of severity to
      categorise them. The findings provided a basis for an analysis of nursing
      assessment and established that they were realised as prognostic judgements.
      Discussion of the structure of the categories led to a possibility that the
      cognitive skill referred to as 'intuition' could be explained by the way in which
      clinical knowledge comes to be organised in memory.

PMID- 8550303
TI  - The role of the continence adviser in England and Wales.
AB  - Continence advice in England and Wales is a relatively new specialism within
      nursing and, over the past 20 years, the number of continence advisers has grown
      substantially. There are, however, no formal qualifications for the role and the
      service has grown up in a piecemeal fashion. A study carried out by the Social
      Policy Research Unit of the University of York sought to answer basic
      quantitative questions about: (1) the number of continence advisers in post,
      their professional backgrounds and so on; (2) the structures within which
      continence advisers work; and (3) the nature of their current practice; as well
      as more attitudinal and developmental questions about the history and future
      development of continence advisers' work.

PMID- 8550304
TI  - Efficacy of patient-controlled analgesia in women cholecystectomy patients.
AB  - The purpose of this comparative study was to examine differences in pain
      intensity, sleep disturbance, sleep effectiveness, fatigue, and vigor between
      patients undergoing cholecystectomy who received either patient-controlled
      analgesia (PCA) or intramuscular (IM) injections of narcotics for postoperative
      pain. The PCA group consisted of 16 women, aged 22-58; the IM group consisted of
      10 women, aged 22-60. Data were collected on patients' postoperative days 1 and
      2. Findings indicated that patients receiving PCA reported less pain on
      postoperative day 1 and less fatigue on postoperative day 2 than patients
      receiving IM injections of narcotics.

PMID- 8550305
TI  - Psychosocial determinants of burnout in geriatric nursing.
AB  - The purpose of this study was to identify determinants of burnout using an
      adapted version of Kobasa's theoretical framework, considering work stressors,
      work support, coping strategies and hardiness. Data were collected through a
      questionnaire mailed to 1990 randomly selected geriatric nurses. A participation
      rate of 77.6% was achieved. T-test, variance analysis and multiple regression
      analysis were conducted. Hierarchical multiple regression analysis indicated that
      49% of the variance was explained by the study variables. Hardiness and work
      stressors were the most important predictors of burnout. The findings are
      discussed in relation to Kobasa's framework, focusing on resources that reduce
      negative effects of geriatric work stressors. Implications for nursing practice,
      management, education and research are proposed.

PMID- 8550306
TI  - The spiritual dimension: its importance to patients' health, well-being and
      quality of life and its implications for nursing practice.
AB  - The spiritual dimension is described and is interpreted as the need for: meaning,
      purpose and fulfillment in life; hope/will to live; belief and faith. As the
      spiritual dimension is important for the attainment of an overall sense of
      health, well-being and quality of life (referred to as the health potential) and
      as illness and hospitalisation can precipitate spiritual distress, patients'
      spiritual needs should be addressed. The nurse's role in spiritual care is
      discussed with reference to the nursing literature.

PMID- 8550307
TI  - The pattern and effect of on call work in transplant coordinators in the United
      Kingdom.
AB  - About 75 transplant coordinators are employed in the United Kingdom to ensure the
      process of organ donation to transplantation. Seventy six per cent of
      coordinators are drawn from the nursing profession. The participation of
      coordinators in on call rotas allows service provision to be maintained
      throughout the 24 hour period. The precise pattern of work and effect on
      participating individuals of this round the clock service provision have not been
      previously described. This study aimed to establish the existing pattern of on
      call rotas and to explore the effects, on health and performance, as perceived by
      coordinators. The findings revealed that 11% (n = 6) of coordinators were working
      1 in 1 rotas and a further 6% (n = 3) a virtual 1 in 1. Where 1 in 2 and 1 in 3
      rotas were reported this was at best as respondents also routinely covered a
      colleagues absence. The main effects of on call work were identified as fatigue
      and a reduction in performance-occasionally in 79% (n = 42) and frequently in 11%
      (n = 6) of cases. Findings related to sleep difficulties, meal regularity and
      quality of off call time suggest a potential for compromised health. These data
      provide a grounding of knowledge into the effect on health and performance of on
      call work, in this group of health service workers, warranting further
      investigation. It is recommended that the frequency of on call work should not
      exceed 1 in 3 with prospective holiday cover and that options such as a partial
      shift system and locum cover should be considered.

PMID- 8550308
TI  - Conflicting attitudes to corneal and organ donation: a study of nurses' attitudes
      to organ donation.
AB  - The demand for transplantable organs and tissues is steadily increasing and
      action is necessary to improve the organ and tissue donation rates. Previous
      research has suggested that nurses have a substantial influence on the rates of
      donation in the clinical area. Nurses (N = 150) were asked to complete a number
      of measures to assess positive and negative attitudes towards cadaveric organ
      donation, with 112 (74.6%) responding. The findings identified conflicting
      attitudes particularly in relation to corneal donation; 25% of the respondents
      would not donate their corneas. Reasons given included fear of disfigurement,
      religious factors such as the need to see into the next life, and dislike of the
      thought of donation of eyes but without knowing why. The majority of the
      respondents were in favour of donation generally and many carried or had signed
      donor cards. Nurses are usually the professionals who have the most contact with
      the patient in the clinical and are therefore able to identify potential donors.
      It seems likely that nurses with conflicting attitudes to donation are less
      likely to undertake the emotional costs involved when relatives of potential
      donors are approached re donation, than those who have more positive attitudes.

PMID- 8550309
TI  - Managing occupational HIV exposures: a Canadian study.
AB  - The findings reported in this paper are part of a larger study that explored how
      nurses cope with the risk of acquiring HIV infection while caring for persons
      with AIDS (PWAs). The data were collected through in-depth interviews with 13
      nurses who cared for PWAs in a large Western Canadian hospital. Seven of these
      nurses perceived that they had been exposed to HIV-infected blood or body fluids.
      This paper describes how these seven nurses coped with actual exposures to HIV
      infected blood or body fluids. Data were analyzed using the methodology of
      grounded theory. Nurses' coping efforts after exposure were grouped into four
      categories: minimizing the effect of exposures, reducing a sense of
      vulnerability, selective disclosure to others, and assigning meaning. Nurses
      minimized the physical effects of exposure through measures such as 'bleeding'
      the needlestick injury and immersing the affected area in bleach solution. Nurses
      reduced their sense of vulnerability by assessing the possibility of harm,
      avoiding situations that aroused fear, and confronting the decision for HIV
      testing. Nurses limited their disclosures to co-workers to avoid rejection and to
      preserve professional self-esteem. Disclousre to significant others was
      influenced primarily by the support nurses perceived they would receive. Finally,
      nurses attempted to assign meaning to the exposure by determining why the event
      occurred and by evaluating the implications it has had on their lives. The
      article concludes with implications for nursing practice.

PMID- 8550310
TI  - Ethical awareness among first year medical, dental and nursing students.
AB  - Ethics is increasingly being included in the training curriculum for health-care
      professionals. However, debate continues around the appropriate content of ethics
      courses for such students and the most relevant teaching approaches which will
      enable students to apply their ethical knowledge in clinical settings. At a time
      when health-care professionals are starting to collaborate more closely in
      multidisciplinary teams, it is appropriate to explore the ethical values held by
      different groups of health professionals. This study sought to ascertain the
      ethical views and knowledge which medical, dental and nursing students have at
      the commencement of their training, to establish their opinions on the most
      important areas of ethical debate in contemporary health care and to examine
      their ethical reasoning in response to a series of vignettes. Students gave
      detailed answers to the questionnaire and the data they provided furnishes useful
      material for those designing and teaching ethics courses.

PMID- 8550311
TI  - Advancing the status of nursing in Egypt: the project to promote the development
      of the High Institutes of Nursing.
AB  - This paper discusses the successes and the challenges of a 3-year project to
      improve the image and status of nursing in Egypt. Several strategies were
      developed and tested. These activities focused on transforming nurse-training and
      the nursing role to the status of professional education and practice. These
      activities have a broad applicability for other countries engaged in similar
      efforts. Successful interventions included the following: (1) A board composed of
      health professionals, health policy-makers, and the nursing trade union was
      established, providing opportunity for interprofessional dialogue; (2) criteria
      that would enable the High Institutes of Nursing (HINs) to quality for university
      faculty status were identified; (3) HINs shared their resources in order to
      enable lesser developed HINs to strengthen their academic curricula, initiate
      graduate degree programs and provide for faculty development; (4) a set of
      standards for nursing clinical practice was developed; and (5) Demonstration
      Clinical Units were established as model settings for improving nursing clinical
      skills. Project trajectories that remain to be accomplished include final
      development and promulgation of a set of nursing standards, development of a
      nursing organization that can speak for professional as well as trade issues and
      upgrading the educational pathway to the nursing profession.

PMID- 8550312
TI  - Adenosine promotes regulation of corneal hydration through cyclic adenosine
      monophosphate.
AB  - PURPOSE: To investigate the cellular mechanisms whereby adenosine increases net
      transendothelial fluid transport by the endothelial cells of the cornea. METHODS:
      Rabbit corneas were isolated and the endothelial surface was superfused while
      thickness was measured with the specular microscope. Cyclic adenosine
      monophosphate (cAMP) was measured in endothelia from fresh and incubated corneas,
      and adenylyl cyclase and phosphodiesterase activities were measured in
      homogenates or the particulate fraction of endothelia from bovine or rabbit.
      Adenosine, adenosine-receptor agonists, dibutyryl cAMP, forskolin, and
      phosphodiesterase inhibitors were used to modulate physiological and biochemical
      parameters. RESULTS: Adenosine, N-ethyl(carboxamido)adenosine, dibutyryl cAMP,
      forskolin, and phosphodiesterase inhibitors all promoted deturgescence of swollen
      corneas and maintained fresh corneas at lower steady state thicknesses than in
      controls. These effects were abolished in the presence of ouabain or 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid or after complete removal of HCO3-
      from the media. Intracellular cAMP was significantly increased by forskolin and
      phosphodiesterase inhibitors and, to a lesser extent, by agonists. Increases in
      cAMP concentration declined rapidly with time. Cyclase activity in the bovine
      tissue was enhanced by agonists and by G-protein activators. Dose-response curves
      of corneal swelling indicated a greater sensitivity to N
      ethyl(carboxamido)adenosine than to the A2 alpha specific agonist CGS 21680.
      CONCLUSIONS: Adenosine increases net endothelial fluid transport through an
      increase in cAMP. The effects are mediated by stimulation of adenylyl cyclase
      through a G-protein coupled to an adenosine receptor, which is most probably of
      the A2 beta subtype. Results suggest that the regulation of corneal hydration by
      adenosine is more probably through stimulation of active transport than through a
      change in permeability, involving either transmembrane fluxes of Na+ or HCO3- or
      another step tightly coupled to these primary events in fluid movement.

PMID- 8550313
TI  - Adhesion of human trabecular meshwork cells to extracellular matrix proteins.
      Roles and distribution of integrin receptors.
AB  - PURPOSE: To examine the adhesion of human trabecular meshwork cells with various
      extracellular matrix (ECM) proteins and to evaluate the roles and distribution of
      integrin receptors. METHODS: Cultured human trabecular meshwork cells were added
      to 96-well plates either uncoated or coated with proteins including fibronectin,
      laminin, and vitronectin, as well as collagen types I, III, IV, V, and VI. After
      incubation for 1 hour, the adhesion of cells was measured. Expression of cell
      surface integrins was determined by cell enzyme-linked immunoadsorbent assay
      (ELISA) and immunoprecipitation. Distribution was visualized by
      immunofluorescence staining using integrin-specific antibodies. For function
      perturbation and peptide inhibition studies, cells were preincubated with either
      integrin antibodies or synthetic peptides before the adhesion assays. RESULTS:
      Human trabecular meshwork cells attached to plates coated with ECM proteins in a
      dose-dependent manner. Fibronectin, vitronectin, and collagen types I and IV were
      the preferred ECM substrates. Cell ELISA revealed the presence of integrins alpha
      1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, beta 1, beta 3, beta 5,
      alpha 5 beta 1, and alpha v beta 3 and the absence of beta 2 and beta 4 on human
      trabecular meshwork cells. Results from immunostaining experiments were
      consistent with those from cell ELISA studies. Attachment of cells to ECM
      proteins was blocked by specific integrin antibodies. Cell adhesion to
      fibronectin and vitronectin was inhibited by peptides containing the Arg-Gly-Asp
      sequence. CONCLUSIONS: Extracellular matrix proteins mediate the adhesion of
      human trabecular meshwork cells in culture. Integrin receptors appear to have
      functional roles in the cell-matrix interactions.

PMID- 8550314
TI  - Posttranslational regulation of type I collagen in corneal endothelial cells.
AB  - PURPOSE: Type I collagen synthesis in corneal endothelial cells does not
      correlate with steady state collagen RNA levels; although substantial amounts of
      alpha 2(I) collagen RNA are present in these cells, type I collagen is not
      detected. This allowed the authors to investigate the possibility of
      posttranscriptional control of type I collagen in corneal endothelial cells.
      METHODS: The alpha 2(I) collagen RNA structures of normal and modulated corneal
      endothelial cells were analyzed by S1 nuclease protection analysis, whereas the
      nucleotide sequences were obtained by rapid amplification of cDNA ends technique.
      In situ hybridization of type I collagen was demonstrated with
      immunofluorescence; synthesis and degradation of the molecule were analyzed by
      pulse-chase experiments and then by immunoprecipitation with antiprocollagen I
      antibody. RESULTS: The cDNA covering the 5'-untranslated region (UTR) of alpha
      2(I) collagen RNA obtained from normal corneal endothelial cells and from
      modulated corneal endothelial cells that predominantly produce type I collagen
      demonstrate identical sequences in their 5' untranslated and coding sequences. In
      both mRNA, the length of the 5'-untranslated segment is 127 nucleotides. There
      were also two AUG codons; the second AUG codon, which is 17 nucleotides upstream
      from the translation initiation codon, is conserved, as observed in human and
      chicken alpha 2(I) mRNA. When the sequence covering the 3'-UTR of corneal
      endothelial alpha 2(I) mRNA was compared with that of alpha 2(I) mRNA obtained
      from the modulated cells, there were differences in only two nucleotides. The
      length of the 3'-untranslated segment of each mRNA is 297 nucleotides up to the
      consensus polyadenylation recognition site (AAUAAAAUAAA), which both cells use.
      Immunofluorescent staining of corneal tissue in vivo demonstrated that the
      corneal endothelium stains with anti-type I collagen antibodies, but there is no
      staining in the underlying Descemet's membrane. In pulse-chase experiments, the
      newly synthesized type I procollagen, composed of pro alpha 1(I) and pro alpha
      2(I) chains as determined by V8 protease peptide mapping, reached the highest
      intracellular level at 45 minutes, after which its detection decreased. Cells
      chased for 120 minutes demonstrated no trace of type I procollagen in the cell
      layer; medium fractions showed no detectable type I procollagen during the entire
      120-minute chase. CONCLUSIONS: These results suggest that type I collagen is
      synthesized in corneal endothelial cells and that such undesired expression is
      regulated at the posttranslational level, perhaps by intracellular degradation.

PMID- 8550315
TI  - Effect of fixation pressure on juxtacanalicular tissue and Schlemm's canal.
AB  - PURPOSE: A quantitative study was performed to compare the effect of two commonly
      used fixation pressures, 0 mm Hg (immersion) and 10 mm Hg (perfusion), on the
      porosity of the juxtacanalicular tissue and the size of Schlemm's canal. METHODS:
      Twelve pairs of human eyes were studied by fixing one eye with perfusion fixation
      and the fellow eye with immersion fixation. Morphometric analysis of the
      juxtacanalicular tissue and Schlemm's canal was performed. Outflow resistance was
      calculated from these measurements and compared with the measured outflow
      resistance obtained in six eyes. RESULTS: Schlemm's canal was narrowed in
      perfusion-fixed eyes, with a 47% smaller cross-sectional area than in immersion
      fixed eyes (P = 0.04). Juxtacanalicular tissue of perfusion-fixed eyes had a
      13.4% increase in the relative amount of empty space when compared with immersion
      fixed fellow eyes (P = 0.04). Solid tissue components were almost equally divided
      among amorphous basement membrane, tendon and sheath material, and cytoplasm. No
      obvious washout of extracellular material was noted in perfused tissue. Measured
      outflow resistance was 100 times larger than outflow resistance of the
      juxtacanalicular tissue calculated from histologic measurements. CONCLUSIONS:
      Perfusion fixation at physiologic intraocular pressure caused a 47% decrease in
      the area of Schlemm's canal and a mean increase of 13.4% in the relative amount
      of empty space in the juxtacanalicular tissue compared with immersion-fixed
      fellow eyes. Perfusion of fixative did not appear to cause washout of
      extracellular material. Perfusion-fixed tissue appears preferable for studies of
      Schlemm's canal and for ultrastructural studies of the aqueous outflow pathways
      within the juxtacanalicular tissue.

PMID- 8550316
TI  - The scotopic electroretinogram of macaque after retinal ganglion cell loss from
      experimental glaucoma.
AB  - PURPOSE: This study describes the dark-adapted electroretinograms (ERGs) of
      macaque monkeys with severe visual field defects and substantial retinal ganglion
      cell loss as a consequence of long-standing ocular hypertension. METHODS:
      Monocular experimental glaucoma was produced by argon laser trabeculoplasty, and
      visual fields were assessed with behavioral static perimetry.
      Electroretinographic responses to brief ganzfeld flashes under fully dark-adapted
      conditions were recorded using DTL fiber electrodes in anesthetized animals. The
      authors quantified retinal layer thickness and cell loss in 1-micron radial
      sections and inspected optic nervous under the light microscope. RESULTS: At the
      lowest intensities, a sensitive negative component of the scotopic ERG, which
      normally peaks approximately 200 msec after stimulus onset, was present in the
      control eyes but was reduced greatly or was virtually absent in the experimental
      eyes of monkeys with severe visual field loss. A previously unreported sensitive
      positive component of the scotopic ERG remained in both eyes. In the control
      eyes, the positive component gave rise to a sharp peak approximately 120 msec
      after stimulus onset, but in the experimental eyes, because of the absence of the
      more delayed sensitive negative potential, it was sustained, lasting as long as
      700 msec. Scotopic a- and b-waves and oscillatory potentials in the experimental
      eyes were not consistently different from control eyes. Ganglion cell and optic
      nerve loss in the experimental eyes was substantial, and there was little other
      obvious retinal damage. CONCLUSIONS: A sensitive negative component is reduced or
      absent from the dark-adapted ERGs of macaque monkeys with severe visual field
      defects and substantial retinal ganglion cell loss as a consequence of long
      standing ocular hypertension.

PMID- 8550318
TI  - Developmentally important DNA elements within the bovine opsin upstream region.
AB  - PURPOSE: Nuclear run-on analysis has documented three categories of opsin gene
      expression during bovine fetal retinal development: basal levels of transcription
      occurring before 6 months gestation; opsin-specific enhanced levels of fetal
      transcription at 7-7.5 months gestation; and a switch from fetal to adult
      transcription, where transcriptional activity acquires a sarkosyl sensitive
      component in the adult. To begin determining the mechanism of these multiple
      levels of gene regulation, DNA regulatory elements within 2.1 kb of the rod opsin
      upstream region were identified in fetal and adult bovine retinal extracts that
      represented the transcriptional activities characteristic of each stage of opsin
      gene expression. METHODS: DNAse I footprint experiments were performed on fetal
      and adult bovine retinal extracts from each of the developmental stages of opsin
      expression. RESULTS: Ten regions of protection were mapped and the level of
      protection was quantitated as a function of the developmental stage. CONCLUSIONS:
      The 10 DNA elements identified fell into three categories of developmental
      protection: those elements that were protected similarly at each developmental
      stage; those elements that were more highly protected when opsin transcription
      was at basal levels (i.e., less than 6 months gestation); and those elements that
      were more highly protected in fetal ages as compared to the adult animal. These
      elements are likely to be important in the developmental regulation of rod opsin
      gene expression.

PMID- 8550317
TI  - Enhanced prostaglandin synthesis after ultraviolet-B exposure modulates DNA
      synthesis of lens epithelial cells and lowers intraocular pressure in vivo.
AB  - PURPOSE: To study the functional significance of prostaglandin synthesis after
      ultraviolet-B (UVB) exposure of cultured human lens epithelial cells and rabbit
      eyes in vivo. METHODS: Prostaglandin E2 (PGE2) was assayed using a
      radioimmunoassay (RIA) and mass spectroscopy. An immortalized human lens
      epithelial cell line (HLE-B3) was exposed to UV irradiation, and the synthesis of
      PGE2 was compared with the rabbit lens epithelial cell line N/N1003A. Intact
      human lenses were exposed to UVB in organ culture. [3H]Thymidine incorporation
      was measured in cultured lens epithelial cells by incubation with the radiolabel.
      The effects of isobutyl methyl xanthine (IBMX), an inhibitor of phosphodiesterase
      and of dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, on
      PGE2 synthesis and DNA synthesis, were determined. Rabbit eyes were exposed to
      UVB radiation in vivo. Intraocular pressure was measured at specific times after
      exposure. Aqueous humor was remove from rabbit eyes, and its PGE2 content was
      measured by RIA. RESULTS: Cultured human lens epithelial cells (HLE), like rabbit
      lens epithelial cells (RLE), showed a dose-dependent increase in basal PGE2
      synthesis 24 hours after UVB exposure. However, the amount of PGE2 synthesis was
      2000-fold higher in the rabbit cells. Ultraviolet-B radiation enhanced the
      incorporation of [3H]thymidine in lens epithelial cells. Pretreatment of cells
      with indomethacin reduce PGE2 synthesis and [3H]thymidine incorporation. The
      human and rabbit cells responded in a similar manner to changes in DNA synthesis
      after UVB exposure. The addition of IBMX or dbcAMP to indomethacin-treated, UVB
      exposed cells restored DNA synthesis toward the levels observed in the UVB
      exposed cells. An increase in the concentration of cAMP was observed in lens
      epithelial cells exposed to exogenous PGE2. PGE2 synthesis in intact human lenses
      also increased twofold 24 hours after UVB exposure. Exposure of the rabbit eye in
      vivo to an optimal dose of UVB produced an increase in the PGE2 levels of the
      lens and the aqueous humor. Measurements of the intraocular pressure (IOP) of the
      animals showed a decrease in IOP by 2.21 +/- 0.66 and 6.45 +/- 0.79 mm Hg (mean
      +/- SEM, P = 0.004, t-test) at 6 and 24 hours after UVB exposure, respectively.
      The decrease in IOP was prevented by pretreatment with indomethacin. Exposure of
      the rabbit lens to UVB radiation in vivo enhanced [3H]thymidine incorporation
      twofold into the lens. Pretreatment of rabbits with indomethacin before exposure
      reduced this response. CONCLUSIONS: Results indicate that UVB exposure enhances
      PGE2 synthesis in HLE cultures as well as in rabbit lenses irradiated in vivo.
      This increased PGE2 synthesis is related to the increase in DNA synthesis
      observed after UVB treatment. The modulation of DNA synthesis in cultured lens
      epithelial cells after UVB exposure may be mediated by a cAMP-dependent
      mechanism.

PMID- 8550319
TI  - Detection of transforming growth factor-alpha mRNA and protein in rat lacrimal
      glands and characterization of transforming growth factor-alpha in human tears.
AB  - PURPOSE: To assess whether the lacrimal gland is a possible site of synthesis of
      transforming growth factor-alpha (TGF-alpha) and to characterize TGF-alpha
      biochemically in human tears. METHODS: Reverse transcription-polymerase chain
      reaction (RT-PCR) amplification was used to analyze rat lacrimal glands for the
      presence of TGF-alpha mRNA. Specific monoclonal antibodies were used to localize
      TGF-alpha immunohistochemically in lacrimal gland tissue of rats. Human tears
      were analyzed for immunoreactive TGF-alpha protein using a specific
      radioimmunoassay, and the molecular weight of TGF-alpha in tears was
      characterized by Western blot analysis. RESULTS: RT-PCR amplification of rat
      lacrimal gland RNA generated a band of the predicted 492 base pairs for TGF-alpha
      mRNA. Immunohistochemical staining of rat lacrimal gland localized TGF-alpha
      protein to lacrymocytes constituting acini but not to interacinar and intraacinar
      ducts of lacrimal glands. Western blot analysis of human tears detected a single
      band at MWt 16,000. Logit transformation of radioimmunoassay data for tears and
      TGF-alpha standard generated parallel displacement lines, indicating the presence
      of immunoreactive TGF-alpha levels in human tears with an average concentration
      of 100 +/- 20 pg/ml (mean +/- SEM). CONCLUSIONS: Rat lacrymocytes synthesize TGF
      alpha mRNA and protein, and human tears contain immunoreactive TGF-alpha,
      suggesting that the lacrimal gland may be an exocrine source for TGF-alpha in
      tears. The single MWt 16,000 form of TGF-alpha in human tears appears to be
      generated by an unusual proteolytically processing of the pro-TGF-alpha
      transmembrane precursor protein.

PMID- 8550320
TI  - Differential distribution of CaM kinases and induction of c-fos expression by
      flashing and sustained light in rat retinal cells.
AB  - PURPOSE: To examine the expression of c-fos proto-oncogene and phosphorylation of
      cAMP responsive element binding (CREB) protein in the rat retina after changes in
      the light-dark condition. METHODS: Rats were exposed to both steady light and
      flashing light and were killed at the end of light exposure. The retinas were
      analyzed by in situ hybridization using single-stranded RNA probes for c-fos
      transcripts and by immunocytochemistry using phosphoSer-133 specific CREB
      antiserum, anti-calcium calmodulin dependent protein (CaM) kinase II, and anti
      CaM kinase IV. RESULTS: c-fos mRNA was expressed in the outer half of the inner
      nuclear layer (INL) and in the ganglion cell layer (GCL) after 30 minutes of
      sustained light. After 30 minutes of flashing light, c-fos expression also was
      detected in the inner border of the INL. Phosphorylated CREB immunoreactive
      nuclei had similar distribution after steady and flashing light. Both CaM kinase
      II and CaM kinase IV, which phosphorylate CREB at Ser 133 in vitro, were
      expressed in the GCL and in the INL. CaM kinase II, however, was localized in the
      inner border of the INL, whereas CaM kinase IV was distributed in the outer half
      of the INL. CONCLUSIONS: These results suggest that the differential expression
      of c-fos mRNA induced by flashing and sustained light may reflect the CREB
      phosphorylation by CaM kinases in a different subpopulation of retinal cells.

PMID- 8550321
TI  - Interobserver reliability of the Teller Acuity Card procedure in pediatric
      patients.
AB  - PURPOSE: To compare interobserver agreement for Teller Acuity Card estimates of
      grating acuity between children with ocular or neurologic abnormalities, or both,
      and age-matched healthy preterm children. METHODS: Subjects were 57 children, 3
      to 38 months of age, who were referred for visual assessment because of diagnosed
      or suspected visual impairment (clinical group), and 57 healthy preterm children
      with no known visual or neurologic abnormalities (control group), each of whom
      was matched to a clinical subject, based on corrected age at the time of testing,
      and type of testing (monocular or binocular). Each child's grating acuity was
      tested by two independent observers. RESULTS: Interobserver agreement of 1 octave
      or better was found in 91% of the monocular and 96% of the binocular clinical
      test-retest comparisons and in 95% of the monocular and 96% of the binocular
      control comparisons. For estimates of interocular acuity difference,
      interobserver agreement of 1 octave or better was found in 88% of clinical
      subjects and 88% of control subjects. Average test time was significantly longer
      in the clinical group (4.1 minutes [SD = 1.9] for monocular and 3.6 minutes [SD =
      1.9] for binocular tests) than in the control group (2.5 minutes [SD = 0.9] for
      monocular and 2.4 minutes [SD = 0.6] for binocular tests), suggesting that
      children in the clinical group were more difficult to test. CONCLUSIONS: Teller
      Acuity Card testing conducted by experienced testers is as reliable in children
      with mild to severe ocular or neurologic abnormalities as it is in healthy
      children, even though children with abnormalities may be more difficult to test.

PMID- 8550322
TI  - Perception of motion smear in normal observers and in persons with congenital
      nystagmus.
AB  - PURPOSE: Despite incessant motion of the retinal image, persons with congenital
      nystagmus (CN) usually do not report that targets are smeared. The authors
      investigated whether the brief stationary glimpses of a target that occur during
      foveation periods in the CN waveform contribute to the alleviation of perceived
      smear. METHODS: Retinal image motion simulating that in jerk nystagmus was
      produced in normal observers (N = 10) who monocularly viewed either a 5-minute or
      a 1 degree luminous disk reflected from a horizontally oscillating mirror.
      Contrast sensitivities to detect each target and to perceive the presence of
      motion smear were determined for two simulated CN waveforms; observers also
      estimated the length and brightness of perceived smear for several suprathreshold
      target luminances. One waveform was a 7 degrees, 4-Hz ramp that included 120 msec
      zero-velocity intervals, simulating the foveation periods in the CN waveform. The
      second waveform lacked the zero-velocity simulated foveation periods. For
      comparison, estimates of perceived smear for physically stationary targets were
      obtained from three observers with CN. RESULTS: Normal observers' contrast
      sensitivities for perceiving smear were nearly identical for the simulated CN
      waveforms with and without a 120-msec foveation period. Estimated length and
      brightness of perceived smear for suprathreshold targets increased similarly with
      luminance for both waveforms. Observers with CN reported substantially less smear
      than did normal observers. CONCLUSIONS: Glimpses of a stationary retinal image
      during simulated foveation periods do not attenuate the perception of motion
      induced smear in normal observers. In persons with CN, the perception of smear
      may be reduced by the extraretinal signals that accompany their eye movements.

PMID- 8550323
TI  - Microglial cells invade the outer retina as photoreceptors degenerate in Royal
      College of Surgeons rats.
AB  - PURPOSE: Photoreceptor degeneration is accompanied by the invasion of phagocytic
      cells into the outer retina of Royal College of Surgeons (RCS) rats. Previous
      studies suggested that these mononuclear phagocytes were blood-borne macrophages
      and not retinal pigment epithelial cells nor Muller glia. Thus, immunospecific
      markers were used to identify these cells and to determine their distribution in
      the dystrophic retina. METHODS: Retinas from RCS and control (RCS-rdy+) rats were
      processed for immunocytochemistry using antibodies against phosphotyrosine, which
      labels both microglial cells and peripheral macrophages, and ED2, which labels
      peripheral macrophages only. As a positive control to demonstrate ED2-labeling of
      peripheral macrophages that enter the retina during injury, experiments were
      performed using needle-punctured Long Evans rat retinas. RESULTS: In normal
      animals, process-bearing, phosphotyrosine-reactive cells were restricted to the
      inner retinal layers and the outer plexiform layer. In early dystrophic retinas,
      phosphotyrosine-reactive cells also were observed in the outer retinal layers.
      The number of phosphotyrosine-labeled cells in the outer retina increased
      substantially in later stages of dystrophy. ED2-reactive cells were observed in
      normal or dystrophic retinas only after needle puncture. CONCLUSIONS: These
      findings suggest that phagocytic cells during the early stages of dystrophy in
      RCS rat retinas are derived from resident microglial cells, not from peripheral
      macrophages. The migration of microglial cells into the outer retina when
      photoreceptor cells begin to degenerate further suggests that they may play a
      major role in photoreceptor cell death in the dystrophic retina.

PMID- 8550324
TI  - Inhibition of pseudomonal ulceration in rabbit corneas by a synthetic matrix
      metalloproteinase inhibitor.
AB  - PURPOSE: To evaluate the effect of the synthetic matrix metalloproteinase
      inhibitor, Galardin, on proteases produced by Pseudomonas aeruginosa (PA) and on
      a rabbit model of Pseudomonas keratitis. METHODS: Protease activities of culture
      broths from Pseudomonas strains PA-28 and W-186 were characterized in vitro by
      gelatin zymography and by digestion of Azocasein in the presence and absence of
      Galardin and the serine protease inhibitor, aprotinin. In a noninfectious in vivo
      experiment, sterile PA culture broth from W-186 was injected intrastromally into
      rabbit corneas that were treated topically with Galardin or vehicle, then
      evaluated clinically and histologically. In an infectious in vivo experiment,
      rabbit corneas were injected with washed PA-28, then treated topically with
      Galardin or vehicle and clinically scored. RESULTS: Gelatin zymography of culture
      broth from W-186 and PA-28 detected two proteases that were both inhibited by
      Galardin. Galardin reduced the digestion of Azocasein by both PA culture broths
      by 99%, whereas aprotinin did not significantly reduce the protease activity of
      PA-28 conditioned broth. Intrastromal injection of sterile W-186 culture broth
      caused rapid corneal destruction that was prevented by topical treatment with
      Galardin. Intrastromal injection of washed PA-28 bacteria resulted in progressive
      corneal melting that was significantly (P < 0.005) delayed, but ultimately not
      prevented, by topical treatment with Galardin. CONCLUSIONS: Pseudomonal protease
      activity in culture broth consisted predominantly of metalloproteinases and were
      effectively inhibited by Galardin in vitro. Topical treatment with Galardin
      prevented destruction of rabbit corneas by bacterial products present in culture
      broth, and it delayed corneal destruction after injection of PA bacteria.
      Galardin may be a useful adjuvant when corneal destruction proceeds despite
      prompt antibiotic treatment.

PMID- 8550325
TI  - Transplantation of human fetal retinal pigment epithelium rescues photoreceptor
      cells from degeneration in the Royal College of Surgeons rat retina.
AB  - PURPOSE: The Royal College of Surgeons (RCS) rat suffers from a well
      characterized, early-onset, and relentless form of photoreceptor cell
      degeneration. It has been shown that allografts of retinal pigment epithelial
      cells from normal perinatal rats have rescue effects in this condition. In
      preparation for human application, the authors determined whether human fetal
      retinal pigment epithelium (RPE) grafts have a photoreceptor rescue effect in RCS
      dystrophic rat retinas. METHODS: Sheets of RPE from human fetal eyes (10 to 16
      weeks gestational age) were isolated according to the authors' recently described
      method. Fragments of the RPE sheets were transplanted to the subretinal space
      within the superior hemisphere. Transplants were performed within the superior
      equatorial region of five dystrophic RCS rats, one eye per animal. A similar
      volume of vehicle was injected into the subretinal space of five age-matched
      control rats, again one eye per rat. All rats were immunosuppressed with daily
      injections of cyclosporine. Using light microscopy, photoreceptor cell nuclear
      profiles of superior equatorial (SE) and inferior equatorial (IE) regions of
      transplanted and sham-injected control animals were counted. RESULTS: Four weeks
      after transplantation, a dramatic rescue effect was observed. Microscopically,
      presumptive donor RPE cells were seen as single pigmented cells and as cell
      clusters in the subretinal space. An outer nuclear layer three to four profiles
      thick was present in the area of the RPE transplant but was nearly absent in the
      rest of the retina, as well as in the retinas of control rats. The number of
      photoreceptor nuclear profiles per 100 microns was 34.7 +/- 2.2 (mean +/- SEM) in
      the SE region of transplanted rats and 3.5 +/- 1.4 in the same region of sham
      injected rats. There were 3.0 +/- 1.0 photoreceptor nuclear profiles in the IE
      region of transplanted rats and 3.5 +/- 1.2 in the IE region of sham-injected
      eyes. No evidence of graft rejection was seen. CONCLUSIONS: This study provides
      the first indication that transplanted human fetal RPE cells are able to rescue
      photoreceptor cells in a model of hereditary retinal degeneration.

PMID- 8550326
TI  - Comparative adrenocholinergic control of intracellular Ca2+ in the layers of the
      ciliary body epithelium.
AB  - PURPOSE: Both nonpigmented epithelia (NPE) and pigmented epithelia (PE) of the
      ciliary body are thought to participate in the formation of aqueous humor and its
      pharmacologic regulation. The aim of this study was to identify the similarities
      and differences in intracellular Ca2+ ([Ca2+]i) changes in each of the two layers
      in response to adrenergic and cholinergic inputs. METHODS: Incubation of the
      Dutch belted rabbit ciliary body (CB) in low-[Ca2+] solution was used to induce
      the functional dissociation of the NPE and PE layers from each other. These
      layers or the intact undissociated CB were loaded with the fluorescent Ca2+
      indicator fura-2 and mounted in superfusion chambers for fluorometric measurement
      of [Ca2+]i. RESULTS: In the NPE of the intact CB epithelium or in the isolated
      NPE, 10 microM acetylcholine (ACh), 1 microM brimonidine (UK 14304), or 1 microM
      epinephrine each elicited minimal rises in [Ca2+]i. On the other hand, the
      combination of either adrenergic drug with ACh resulted in large mobilizations of
      this cation. The alpha 1-adrenergic agonist phenylephrine was unable to induce
      Ca2+ mobilization in the isolated NPE and failed to do so in 10 of 12 intact CB
      specimens. In the isolated PE, both epinephrine and phenylephrine elicited
      substantial similar [Ca2+]i increases, ACh induced a smaller and slower rise, and
      the response to its combination with either adrenergic drug was essentially
      additive. UK 14304 (+/- ACh) had no measurable effect in these cells.
      CONCLUSIONS: Each layer of the CBE exhibits distinct alpha-adrenergic control
      mechanisms. The NPE contains an alpha 2-adrenergic mechanism highly dependent on
      the cholinergic tone. The PE, in contrast, contains an alpha 1-adrenergic pathway
      that operates independently of cholinergic input. This segregation of mechanisms
      provides a basis for highly complex regulatory responses in the intact,
      syncytially organized ciliary body epithelium.

PMID- 8550327
TI  - The effect of light history on the aspartate-isolated fast-PIII responses of the
      albino rat retina.
AB  - PURPOSE: To assess the effect of light-rearing history on the photon-capturing
      ability, amplitude, and kinetics of the fast-PIII response of the retina.
      METHODS: Albino rats were raised on 12-hour light-12-hour dark cycles, with
      illumination at 3 lux or 200 lux, and killed at approximately 12 weeks. Retinal
      rhodopsin content was measured spectrophometrically. The morphology of the rod
      outer segments (ROS) and the thickness of the outer nuclear layer were determined
      histologically. Electroretinograms of isolated retinas to 3-microsecond flashes
      were recorded. The kinetics of fast PIII responses were assessed with a model of
      the phototransduction cascade. RESULTS: Total rhodopsin of 200 lux animals was
      reduced to 60% that of 3 lux animals: 2.3 +/- 0.2 versus 1.4 +/- 0.1 nmol/eye
      (mean +/- SD). Length of ROS of 200 lux animals was reduced to 68% of the length
      of that of 3 lux animals: 20.1 +/- 1.2 versus 13.7 +/- 0.5 microns. The saturated
      amplitude of fast PIII of 200 lux animals was reduced to 56% that of the 3 lux
      group: 134 +/- 27 versus 239 +/- 37 microV (T = 22 degrees C). Fast PIII
      responses of both groups are well described by the kinetic model before slow PIII
      intrusion (up to 100 ms). Estimated kinetic parameters of the transduction
      cascade did not differ reliably between the two groups. CONCLUSIONS: Diminished
      saturated amplitude of fast PIII in 200 lux animals is accounted for by the
      hypothesis that fast PIII is directly proportional to the rod photocurrent and by
      the finding that the ROS of 200 lux animals are short compared to those of 3 lux
      animals. Similarity in estimated kinetic parameters of phototransduction suggests
      that the rods of the two groups differ little in the biochemistry underlying the
      activation phase of phototransduction.

PMID- 8550328
TI  - A neutrophil chemoattractant is released from cellular and extracellular
      components of the alkali-degraded cornea and blood.
AB  - PURPOSE: A tripeptide chemoattractant(s) for neutrophils has been shown to
      release from alkali-degraded cornea. This study is designed to determine the
      source of the chemoattractant(s). METHODS: Whole corneas were degraded in 1 N
      NaOH for 10 minutes, 30 minutes, 1 hour, 4, 8, 24, and 48 hours to determine an
      optimal duration of alkali exposure for production of the chemoattractant. Whole
      cornea, cornea minus epithelium, cornea minus endothelium, and stroma alone were
      degraded in 1 N NaOH for 4 hours to determine the relative contribution of each
      corneal layer. In a separate experiment, epithelium alone, endothelium alone,
      cultured keratocytes alone, or bovine corneal collagen were treated separately in
      1 N NaOH for 4 hours. Finally, human plasma, platelets, polymorphonuclear
      leukocytes (PMNL), and red blood cells were treated separately in 1 N NaOH for 4
      hours to determine if a similar chemoattractant was released from alkali-treated
      noncorneal tissue. Neutralized suspensions of all samples were ultrafiltered and
      dialyzed. The chemotactic potential of each sample was determined in the
      polarization assay. RESULTS: Activation of the PMNL polarization response
      increased with the duration of exposure of corneal tissue to alkali, peaking at 6
      hours. Release of the chemoattractant from alkali-degraded corneal tissue showed
      a significant decrease when the epithelium was removed from the stroma. All
      tissue layers showed a PMNL polarization response when treated with alkali. The
      response decreased from epithelium > endothelium > cultured keratocytes >
      collagen. Alkali degradation of human blood components, including plasma, showed
      significant polarization responses ranked in the following order: plasma > PMNL >
      tendon collagen > platelets = red blood cells. CONCLUSIONS: This study
      demonstrates that the tripeptide chemoattractant(s) is released from all layers
      of the cornea after alkali injury. The substance released from blood components
      is of similar size and biologic activity as that found in the cornea, but its
      exact molecular composition is yet to be determined. Timed response of alkali
      degradation determined the optimal conditions for generation of the
      chemoattractant(s) including clinically relevant time intervals.

PMID- 8550329
TI  - Peptidergic innervation of the primate meibomian gland.
AB  - PURPOSE: To localize and characterize nerves in primate meibomian glands using
      immunohistochemical staining for neuropeptides and neuronal enzymes. METHODS:
      Upper eyelids were obtained from seven rhesus monkeys (Macaca mulatta) and one
      cynomolgous monkey (Macaca fascicularis). The tissues were fixed either by
      immersion in Zamboni's fixative or by transcardiac perfusion with
      paraformaldehyde and glutaraldehyde and were then postfixed. Cryostat tissue
      sections of the lids were stained by immunohistochemistry using rabbit antisera
      to neuron-specific enolase (NSE), tyrosine hydroxylase (TH), neuropeptide Y
      (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide
      (CGRP), and substance P (SP), followed by a fluorescence visualization system.
      RESULTS: Used as a marker for the overall nerve distribution, NSE antibodies
      revealed abundant smooth and varicose nerve fibers closely apposed to the
      basement membranes of acini of the meibomian glands. Numerous nerve fibers near
      the meibomian gland acini were immunoreactive for NPY and VIP, but nerve fibers
      containing TH, CGRP, and SP were more sparse in the meibomian glands. Nerve
      fibers also were visualized in other eyelid structures, including conjunctiva,
      epidermis, hair follicles, and subconjunctival lymphoid follicles. CONCLUSIONS:
      The meibomian glands of rhesus and cynomolgous monkeys are richly innervated by
      diverse nerve fiber types. The immunohistochemical staining suggests a largely
      parasympathetic origin for this innervation, with relatively smaller
      contributions from sympathetic and sensory sources. These findings also suggest
      that meibomian gland secretion is under the control of diverse neurotransmitter
      neuromodulator mechanisms.

PMID- 8550330
TI  - Paradoxic effect of anti-CD4 therapy on lacrimal gland disease in MRL/Mp-lpr/lpr
      mice.
AB  - PURPOSE: MRL/Mp-lpr/lpr mice (MRL/lpr) spontaneously develop lacrimal gland
      inflammatory lesions and are a model for the human disease Sjogren's syndrome.
      Therapy with monoclonal antibodies (mAb) to CD4 ameliorates the autoimmune renal,
      vasculitic, and intraocular inflammatory lesions in MRL/lpr mice. The effect of
      anti-CD4 mAb therapy on lacrimal gland immunopathology was evaluated. METHODS:
      From 1 to 5 months of age, MRL/lpr mice were treated with weekly intraperitoneal
      injections of 2 mg anti-CD4 mAb, after which they were killed and their lacrimal
      glands were removed for histologic evaluation and immunocytochemistry. Control
      mice were administered weekly intraperitoneal injections of either saline or
      normal rat immunoglobulin. RESULTS: Anti-CD4 mAb treatment produced no reduction
      in lacrimal gland inflammation but did change its morphology. In control mice,
      there were multiple sharply delineated foci of inflammatory cells in the lacrimal
      gland, whereas in anti-CD4 mAb-treated mice, there was a more diffuse
      inflammation surrounding ill-defined foci that spread throughout the gland.
      Immunocytochemistry revealed that in control mice, lesions were composed
      predominantly of CD4+ T cells, but in anti-CD4 mAb-treated mice, CD8+ T cells
      predominated. CONCLUSIONS: Although anti-CD4 mAb therapy of MRL/lpr mice
      eliminated autoimmune renal disease, autoantibody formation, and ocular
      inflammatory disease, it had a paradoxic effect on lacrimal gland lesions.
      Lacrimal gland lesions in the anti-CD4 mAb-treated mice were not decreased, but
      they had a different morphology and a different immunocytochemical profile.

PMID- 8550331
TI  - Genetic predisposition to coronavirus-induced retinal disease.
AB  - PURPOSE: Retinal inflammatory and degenerative processes in humans and animals
      frequently are associated with genetic factors. The murine coronavirus, mouse
      hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult
      BALB/c mice. The genetic constitution of the host and the virus serotype can be
      critical factors in determining the outcome of a virus infection. The purpose of
      this study was to evaluate the possible role of host genetics in murine
      coronavirus-induced retinal disease. METHODS: JHM virus was inoculated by the
      intravitreal route into BALB/c, CD-1, and A/J mice. At varying times after
      inoculation, eye tissues were evaluated histologically. Antibody responses to the
      virus were evaluated by neutralization assays. RESULTS: JHM virus induces a
      biphasic retinal disease in BALB/c mice. In the early phase, 1 to 7 days after
      inoculation, retinal vasculitis is observed. The second phase, characterized by
      retinal degeneration in the absence of inflammation, is seen by day 10 and
      progresses for several months. There is a similar biphasic disease process in JHM
      virus-infected A/J mice. However, retinal changes are less severe than those seen
      in BALB/c mice. Retinal tissue damage induced by JHM virus in CD-1 mice is
      different. Only the early phase of the disease, consisting of retinal vasculitis,
      was observed. These CD-1 mice do not develop the retinal degenerative disease. In
      fact, after day 10, the retina has a normal appearance. These differences in
      retinal tissue damage are seen over a wide range of infectivity of the virus
      inocula. Virus concentrations ranging from 10(1.4) to 10(4.4) TCID50/5
      microliters were capable of inducing both inflammation and degeneration in BALB/c
      mice, whereas, the highest concentration of virus (10(4.4) TCID50/5 microliters)
      in CD-1 mice resulted in only the early inflammatory changes. CONCLUSIONS: The
      authors show that the genetics of the host can profoundly affect the nature of
      retinal tissue damage. These studies substantiate the concept that a virus can
      indeed trigger retinal degenerative processes in genetically susceptible hosts.

PMID- 8550332
TI  - Endothelial barrier function and Na+/K(+)-ATPase pump density in herpetic stromal
      disease.
AB  - PURPOSE: Corneal edema is a significant component of the various forms of herpes
      simplex virus type 1 (HSV-1)-induced stromal disease. Maintenance of corneal
      thickness, a reflection of corneal hydration, depends on a physical barrier
      formed by endothelial cell-cell junctions and by the activity of Na+/K(+)-ATPase
      pumps that regulate ion flux and thus influence water movement through this cell
      layer. These functions were measured in corneas with increased corneal thickness
      caused by HSV-1-induced stromal disease to determine their contribution to the
      pathogenesis of the edema. METHODS: Stromal disease with corneal edema was
      induced in rabbits by intrastromal injection of the RE strain of HSV-1. At
      various times after infection, during the development of and recovery from
      stromal disease, endothelial barrier function and Na+/K(+)-ATPase pump sites were
      measured in excised rabbit corneas. RESULTS: The endothelial permeability
      coefficient, Ktrans, for 14C-dextran, 3H-inulin, and 14C-mannitol, were not
      altered significantly during periods of maximal corneal edema and stromal
      disease. Endothelial Na+/K(+)-ATPase pump density, as measured by ouabain
      binding, showed a statistically significant (P < 0.05) decrease in HSV-1-infected
      corneas during peak edema compared to mock antigen-injected or uninjected control
      corneas. Pump density returned to baseline values by 24 days after infection,
      concurrent with the resolution of corneal edema. CONCLUSIONS: These results
      indicate that corneal endothelial barrier function was not altered in this form
      of HSV-1-induced stromal edema; however, pump density was reduced significantly.

PMID- 8550333
TI  - Experimental model of light focusing of the peripheral cornea.
AB  - PURPOSE: Epidemiologic studies have shown that the onset of cortical cataract
      occurs primarily in the inferonasal human lens and that the incidence of cortical
      cataract is correlated with ultraviolet light. Ray tracing analysis has suggested
      that the peripheral cornea concentrates light on the opposite peripheral lens and
      that the nose and orbit block peripheral light, except temporally, resulting in a
      relative concentration of light on the inferonasal lens. Studies were performed
      to test these theories. METHODS: A model cornea and anterior chamber, set on a
      disc of light-sensitive paper, was placed in the orbit of a human skull coated
      with wax to simulate soft tissue. The "eye" was exposed to summer sunlight at
      various times of day, with and without sunglasses. Discs from the different
      experimental groups were scanned, and the digitized images were analyzed
      densitometrically using image analysis software. RESULTS: With the head upright,
      the inferonasal section of the disc exhibited the most intense exposure under all
      lighting conditions. Sunglasses decreased the intensity of overall light exposure
      but did not eliminate the inferonasal bias. Only blocking the temple eliminated
      this effect. CONCLUSIONS: This model supports the idea that the peripheral cornea
      focuses light on the inferonasal portion of the human lens. These results may
      explain the correlation between light and the location of cortical cataract.

PMID- 8550334
TI  - Determination of excimer laser ablation rate of the human cornea using in vivo
      Scheimpflug videography.
AB  - PURPOSE: To determine in vivo the amount of human corneal tissue removed by each
      excimer laser pulse, the so-called ablation rate, during photorefractive
      keratectomy (PRK). There is confusion in the literature because the
      experimentally determined ablation rate of 0.4 to 0.5 microns per pulse differs
      from the nominal ablation rate of 0.23 to 0.3 microns per pulse, which is the
      value used in clinical procedures. METHODS: Eleven eyes of 11 patients were
      treated with PRK for correction of myopia. The corneal curvature was determined
      by Scheimpflug videography before and immediately after surgery. Starting from
      this curvature change, the authors calculated the real ablation rate. RESULTS:
      The real ablation rate is coincident with the nominal ablation rate and differs
      significantly from the ablation rate derived from deep keratectomy experiments.
      CONCLUSIONS: The outer layers of the cornea show significantly different ablation
      behavior than the deeper stroma. This information has clinical relevance for the
      predictability of intrastromal excimer laser procedures.

PMID- 8550335
TI  - Vitamin E, retinyl palmitate, and protein in rhesus monkey retina and retinal
      pigment epithelium-choroid.
AB  - PURPOSE: To measure the amounts of vitamin E, retinyl palmitate, and protein in
      the primate retina and its supporting tissues-the retinal pigment epithelium and
      choroid. To compare the amounts and concentrations of these materials in the
      central retina with those in the peripheral retina and to compare the
      concentration of vitamin E in the retina with that in plasma. Finally, to compare
      these results in rhesus monkey with existing measurements in humans. METHODS:
      Ocular tissues from rhesus monkeys (Macaca mulatta) were extracted with a two
      phase solvent system. Components in the extract were separated by reverse-phase
      high-pressure liquid chromatography. Two detectors in series monitored the
      effluent: Vitamin E was quantified with an internal standard and fluorescence
      detection, whereas retinyl palmitate was quantified with an external standard and
      ultraviolet light detection. RESULTS: Amounts of vitamin E, retinyl palmitate,
      and protein in tissues from rhesus monkey compared reasonably well with those
      reported for humans. The content of vitamin E in the peripheral neural retina was
      moderately correlated with its protein content and, to a greater extent, with the
      concentration of vitamin E in the plasma; however, the content of vitamin E in
      the central neural retina correlated only with the amount of protein in the
      central neural retina. CONCLUSIONS: These results are consistent with rhesus
      monkey as a model for the use of vitamin E by human ocular tissues. The amount of
      vitamin E in the central neural retina appears to be more closely regulated than
      the amount of vitamin E in the peripheral neural retina.

PMID- 8550336
TI  - Radial distribution of tocopherols in rhesus monkey retina and retinal pigment
      epithelium-choroid.
AB  - PURPOSE: To map vitamin E as a function of distance from the foveal center in the
      primate retina and retinal pigment epithelium (RPE)-choroid. METHODS: Eyecups
      from rhesus monkeys were dissected with circular trephines so that the innermost
      disc, centered on the fovea, was in the center of a series of concentric rings.
      Two different types of dissection were performed. For one type, the authors used
      circular trephines with diameters of 1, 4, 8, and 10 mm (1,4-D), whereas for the
      other type the diameters were 2, 5, 8, and sometimes 10 mm (2,5-D). When
      possible, the neural retina was separated from the RPE-choroid. Tissues were
      analyzed for vitamin E, retinyl palmitate, and protein. RESULTS: Surface area,
      volume, and protein were used as indexes of the amount of tissue analyzed.
      Distributions of vitamin E in neural retina were dependent on the tissue metric
      used and type of dissection performed. However, regardless of the tissue metric
      used, the central 1-mm disc of the 1,4-D was, on average, higher in vitamin E
      content than was the central 2-mm disc of the 2,5-D. This was particularly true
      when volume was the tissue metric. From the average values of vitamin E in a
      series of concentric discs, a composite plot of the vitamin E concentration in
      the neural retina was generated that took into consideration both types of
      dissection. That plot displayed a local maximum in the fovea and then
      precipitously declined to a minimum in the region between 0.5 and 1.0 mm
      eccentricity (near the foveal crest); at greater eccentricities, the vitamin E
      concentration rose to a value similar to that in the fovea, i.e., the composite
      plot indicated that vitamin E has a V-shaped distribution in the central neural
      retina. Vitamin E distribution in the RPE-choroid, with surface area as the
      tissue metric, also was measured. For this tissue, the foveal region displayed a
      local maximum. CONCLUSIONS: By combining the results of two different types of
      dissection, the authors found that in the neural retina, vitamin E displayed a
      minimum near the foveal crest. This minimum correlated anatomically with the site
      at which areolar (geographic) atrophy frequently occurs in retinal pigment
      epithelial cells in the human disease, age-related macular degeneration.

PMID- 8550337
TI  - Macrophages in the retina of normal Lewis rats and their dynamics after injection
      of lipopolysaccharide.
AB  - PURPOSE: To investigate the density, distribution, and morphology of macrophages
      (bone marrow-derived microglia) and major histocompatibility complex (MHC) class
      II-positive cells in the retina of Lewis rats and the dynamics of these cells
      after systemic lipopolysaccharide (LPS) injection. METHODS: Immunohistochemistry
      was carried out using monoclonal antibodies specific to monocytes and macrophages
      (ED1, ED2) and MHC class II-positive cells (OX-6) on whole-mounts of the retina
      obtained from Lewis rats before and at different time points after footpad
      injection of 200 micrograms of LPS. RESULTS: The inner layers of the normal
      retina contained a network of macrophages, whereby ED1 and ED2 staining revealed
      similar results. Macrophages were either dendritiform or pleiomorphic in
      morphology, with the former predominant. The density of positive cells was higher
      at the peripheral part and the periequatorial part (271 +/- 10 cells/mm2 and 267
      +/- 9 cells/mm2, respectively) than at the posterior part (196 +/- 11 cells/mm2;
      P < 0.0001 in both cases). Lipopolysaccharide injection induced an early
      adherence of monocytes to retinal blood vessels, followed by a massive influx of
      the macrophages into the retina. The ED1-ED2 positive cells showed a variety of
      morphologic appearances: large round cells, pleiomorphic cells, and dendritiform
      cells. Pleiomorphic cells were striking at 48 hours, whereas dendritiform cells
      were predominant in the whole retina at 72 hours and thereafter. On day 14, the
      dendritiform cell numbers returned to approximately preinjection levels. Major
      histocompatibility class II-positive cells could not be found in the normal
      retina, nor after LPS injection. CONCLUSIONS: The network of MHC class II
      negative microglia in the retina were studied. These cells may play an important
      role in immunoregulation and stability of the immunologic microenvironment within
      the retina. Systemic LPS injection was followed by a massive influx of
      macrophages into the retina. The absence of MHC class II-positive cells in the
      retina after LPS challenge may be an important protective mechanism against
      possible autoimmune damage.

PMID- 8550338
TI  - Hypoglycemic hyperemia in retina of newborn pigs. Involvement of adenosine.
AB  - PURPOSE: To determine whether retinal blood flow increases in response to
      perinatal hypoglycemia and whether the vasodilator adenosine is involved in
      mediating the hyperemic response. METHODS: Retinal fluorescein videoangiography
      was undertaken in intact eyes of isoflurane-anesthetized piglets using
      intracarotid injections of sodium fluorescein. Angiograms were recorded to
      videotape and analyzed off-line by image analysis software to determine stimulus
      induced changes in mean arteriovenous transit times, and arteriolar and venular
      diameters, from which retinal blood flow was calculated. Two groups of animals
      were rendered hypoglycemic (blood glucose = 19 +/- 1 mg/dl) by insulin (25 IU/kg,
      intravenously), and angiograms were obtained at 10-minute intervals for 0.5 hour
      of hypoglycemia. One group (n = 5) served as controls. In the other (n = 5), the
      nonspecific adenosine receptor antagonist 8-phenyltheophylline (8PT) was
      administered intravenously approximately 15 minutes before hypoglycemia to
      examine the role of adenosine in the hemodynamic response to hypoglycemia.
      RESULTS: Acute hypoglycemia was associated with an increase in mean retinal blood
      flow of 94 +/- 18% (P < 0.002). However, in animals pretreated with 8PT, this
      hyperemic response was severely attenuated, primarily by an effect on
      arteriovenous transit time. In these latter animals, mean retinal blood flow only
      increased 19 +/- 10% in response to hypoglycemia (P = 0.13 versus normoglycemic
      baseline; P = 0.007 versus untreated hypoglycemic animals). All other hemodynamic
      variables were similar between animal groups. CONCLUSIONS: Acute hypoglycemia
      causes a compensatory increase in retinal blood flow in the perinatal period.
      Because the adenosine receptor antagonist 8PT attenuated this hyperemic response,
      it is concluded that adenosine is involved in eliciting the increase in retinal
      blood flow that accompanies hypoglycemia.

PMID- 8550339
TI  - Immunohistochemical characterization of developing and mature primate retinal
      blood vessels.
AB  - PURPOSE: To characterize developing retinal blood vessels with vascular markers
      and to relate the histochemical profile of maturing vessels to morphologic stages
      in retinal vascular development. METHODS: Vessels were examined in frozen and
      paraffin-embedded retinas and in wholemounts of Macaca monkeys ranging in age
      from fetal day 75 (F75) to adulthood. Endothelial cells were visualized
      immunohistochemically using antisera to von Willebrand's factor and CD31 with
      lectins Ulex europaeus, Bandeiraea simplicifolia, peanut agglutinin, Ricinis
      communis, and wheat germ agglutinin, and by ATPase and ADPase enzymatic
      histochemistry. Antibodies to vascular basement membrane and matrix markers
      laminin, fibronectin, and collagen types I and VIII, and antisera recognizing
      cell cycle-specific nuclear proteins (cyclin, Ki-67, Mib-1) also were used.
      RESULTS: Newly formed and mature vessels were reactive with reagents specific for
      CD31, von Willebrand's factor, types I and VIII collagens, laminin, fibronectin,
      U. europaeus, R. communis, and peanut agglutinin. Wheat germ agglutinin labeled
      vessels only after pretreatment with neuraminidase. All vascular markers appeared
      simultaneously, but some were distributed differentially between capillaries and
      larger vessels, along the central-peripheral extent of a vascular plexus, and
      among different vascular laminae. Markers of vessels failed to label spindle
      shaped presumed vascular precursor cells lying peripheral to the advancing
      vessels during development. Spindle cells exhibited cyclin, Ki-67, and Mib-1
      immunoreactivity. CONCLUSIONS: Immature and mature vitread and sclerad vessels
      displayed histochemical profiles that were qualitatively similar but that had
      subtle quantitative differences. Results do not support identification of spindle
      shaped cells as vascular precursors in the developing monkey retina and are
      discussed in relation to mechanisms of retinal vascularization.

PMID- 8550340
TI  - Aspirin, interleukin-3 and the antiphospholipid syndrome.

PMID- 8550341
TI  - Modulation of experimental systemic lupus erythematosus.

PMID- 8550342
TI  - Prolactin, bromocriptine and autoimmune diseases.

PMID- 8550343
TI  - Pathogenicity of anti-basement membrane (NC1) antibodies: an experimental
      Goodpasture's syndrome.

PMID- 8550344
TI  - Pathogenic aspects of systemic lupus erythematosus.

PMID- 8550345
TI  - Celiac disease and autoimmunity.

PMID- 8550346
TI  - Migrating T lymphocyte's interactions with blood vessel walls and extracellular
      matrix during inflammatory episodes.

PMID- 8550347
TI  - Adjuvant arthritis in Lewis rats can be suppressed by immunoglobulins from
      arthritis-resistant strains.

PMID- 8550348
TI  - Kadishman's tree, Escher's angels, and the immunological homunculus.

PMID- 8550349
TI  - Schizophrenia: a new frontier in developmental neurobiology.
AB  - Evidence from diverse sources, including postmortem investigations, in vivo
      imaging studies and animal models, suggests that schizophrenia has its origins in
      early cortical maldevelopment, which in turn may lead to dysfunctional
      connectivity during brain maturation and clinical symptomatology in early
      adulthood. Antipsychotic drugs, including the atypical agent clozapine, appear to
      act at key sites involved in higher cortical-limbic connectivity, possibly
      mediated by a variety of neurotransmitters. Studies of gene expression may
      provide a better understanding of how antipsychotic drug effects are integrated
      at the postsynaptic level. The data from schizophrenia research are discussed
      within a neurodevelopmental framework.

PMID- 8550351
TI  - Prevalence of cognitive dysfunction and hypothyroidism in an elderly community
      population.
AB  - Cognitive function was assessed in 801 elderly subjects (aged 65-92 years) using
      the Mini Mental State Examination (MMSE). The mean (+/- SD) MMSE score in the age
      group 65-70 years was 27.8 +/- 5.6, and the score declined to 22.3 +/- 7.8 at the
      age 85-90 (P = 0.001). Abnormal MMSE scores (less than 24) were found in 5.2% of
      the subjects aged 65-70 and gradually increased with age to 35.5% in the age
      group of 85-90. Serum thyroid-stimulating hormone (TSH) levels were determined in
      751 subjects. Elevated TSH (> 4.5 mIU/l) were detected in 112 people (14%). The
      prevalence of hypothyroidism was higher in females (18.2%) than in males (9.7%).
      MMSE scores in 39 patients (14 males and 25 females) with untreated
      hypothyroidism were compared to the scores of 570 euthyroid elderly controls (235
      males and 335 females). The mean +/- SD MMSE scores were 27.0 +/- 2.1 in
      hypothyroid males vs. 26.0 +/- 4.7 in male controls and 25.0 +/- 7.7 in
      hypothyroid females vs. 25.0 +/- 6.6 in female controls. The scores in the
      hypothyroid patients were not significantly different from the controls. Our data
      suggest that: a) the average cognitive performance declines with age; b) the
      percentage of subjects with abnormal MMSE scores increases with age, and is
      higher in females than in males; c) the prevalence of hypothyroidism in the
      elderly population is 14% and is higher in females (18%) than in males (10%); and
      d) mild untreated hypothyroidism is not associated with cognitive impairment.

PMID- 8550350
TI  - Serum pepsinogen I in childhood Helicobacter pylori gastritis: its relation to
      mucosal peptic activity.
AB  - Serum pepsinogen I (PG I) levels are raised in children with Helicobacter pylori
      gastritis. To ascertain if this is due to increased production or to increased
      secretion of pepsin by chief cells, we measured mucosal peptic activity in antrum
      and gastric body mucosal homogenates and correlated it to serum PG I levels in
      122 children with and without H. pylori gastritis. In patients infected with H.
      pylori, mucosal peptic activity was decreased when compared to control and to
      children with non H. pylori gastritis. Serum PG I levels were increased (P <
      0.001) and were inversely related to mucosal peptic activity (P < 0.01). These
      findings suggest that H. pylori can promote a leakage of pepsinogen into the
      circulation.

PMID- 8550352
TI  - Age, seasonality and health.
AB  - Seasonal effects on mood and other components of functional status have been
      demonstrated in large segments of the general population but have received little
      attention in primary care patients. In the present study on adult members of a
      communal settlement (kibbutz) in Israel, seasonality and functional status were
      measured in both the winter and summer seasons in the same patients. Patients
      under age 65 had better overall health ratings than those 65 and over in both
      winter and summer. Overall health ratings were better in summer for those under
      65 but were unchanged in the older group. Summer and winter seasonality scores
      were more constant in the younger group than in the older patients. We conclude
      that both age and seasonality need to be considered when measuring functional
      status in primary care patients.

PMID- 8550353
TI  - Vasculitis 1995: new concepts in pathophysiology.

PMID- 8550354
TI  - Scapulothoracic dissociation: a case report.
AB  - Scapulothoracic dissociation has been described as a "closed traumatic
      forequarter amputation" and is characterized by massive soft tissue swelling of
      the shoulder, lateral displacement of the scapula, neurovascular injuries
      (brachial plexus, subclavian artery), an osseous-ligamentous injuries. In
      addition to the lateral displacement of the scapula, an acromioclavicular
      separation, a displaced fracture of the clavicle or sternoclavicular separation
      can be identified on plain X-rays. This injury pattern has been infrequently
      reported. We present a patient who had a previously unreported combination of
      roentgenographic findings, and in whom the diagnosis was revealed by computed
      tomographic evaluation.

PMID- 8550355
TI  - Public health in Jewish lore--on workers and teachers.

PMID- 8550356
TI  - Nurses--an integral part of the medical team.

PMID- 8550357
TI  - Facial pain as a symptom of nonmetastatic lung cancer.
AB  - Patients with nonmetastatic lung cancer may rarely experience facial pain as a
      presenting symptom, during the course of the disease or upon recurrence of the
      disease. This study reviews a 10-year experience at Mayo Clinic. The aim of this
      study was to (1) further characterize the clinical features of facial pain as a
      symptom of nonmetastatic lung cancer, and (2) assist clinicians in recognizing
      this association. Ten cases were identified. All patients complained of severe,
      aching, facial pain typically aural-temporal in location, ipsilateral to the lung
      cancer. Six of the 10 cases involved the left side. Recent weight loss was
      present in 7 of 10 patients, with an elevated sedimentation rate in 6. Digital
      clubbing was documented in three. Neurologic examinations and neuroimaging were
      normal in all patients. Lumbar puncture, when performed, was normal. Facial pain
      preceded the diagnosis of lung cancer by 1 to 24 months. In three patients,
      facial pain was the initial symptom of tumor recurrence. Four of the 10 tumors
      were adenocarcinoma; radiation with or without chemotherapy appears to be the
      treatment of choice for the facial pain. The presumed mechanism is local invasion
      of the vagus nerve. In suspected cases, a chest x-ray and chest CT are indicated.

PMID- 8550358
TI  - Identification and treatment of sleep apnea in patients with chronic headache.
AB  - This study investigates the relationship between nocturnal or morning headache
      and obstructive sleep apnea syndrome (sleep apnea). It is not known if headache
      of any type is more common in patients with sleep apnea than in other patients,
      but morning headache is a symptom of sleep apnea. A method is needed for
      identifying patients with chronic headache who might benefit from evaluation and
      treatment of sleep apnea. We performed a retrospective assessment of frequency of
      morning headache in patients grouped according to final diagnosis: sleep apnea (n
      = 72), periodic leg movements of sleep (n = 28), and psychophysiologic insomnia
      (n = 42). Prospective overnight sleep studies were obtained in a different group
      of 19 patients who presented for evaluation of headache. We selected certain
      patient characteristics as possibly indicative of sleep apnea-related headache.
      The retrospective study showed that 24% of patients with sleep apnea had frequent
      morning headache, which was not different from the other groups. In the separate
      group of 19 patients with chronic headache and suspected sleep disorder, 17 had
      sleep apnea. Nasal continuous positive airway pressure was prescribed to 14
      patients. Marked improvement in headache occurred and persisted in 4 patients and
      moderate improvement in 3. Responders to therapy were more likely to have
      vascular headaches than mixed or tension headaches, more severe sleep apnea, and
      a nocturnal or morning timing to their headaches. However, there was large
      overlap in severity of sleep apnea and likelihood of response. We conclude that
      morning headache is not more common in sleep apnea than in other sleep disorders.
      However, over 30% of patients with chronic headache and other symptoms of sleep
      apnea have significant improvement in headache after treatment of sleep apnea.

PMID- 8550359
TI  - The relationship between headaches and sleep disturbances.
AB  - The relationship between headaches and sleep disturbances is complex and
      difficult to analyze. Both symptoms may have causal relations, or may be
      associated in the same patient with mutual reinforcements. We studied 25 patients
      presenting with morning or nocturnal headaches. Standard headache diagnosis and
      polysomnography were performed. After polysomnography, the diagnoses were
      reevaluated. The main headache entities were cluster, chronic paroxysmal
      hemicrania, migraine, tension, combined headache, and chronic substance abuse
      headache. For each group, headache, sleep data, and changes in diagnosis are
      discussed. The diagnosis was changed in 13 patients; the final diagnoses were
      periodic movements of sleep, fibromyalgia syndrome, and obstructive sleep apnea.
      The diagnoses of cluster headache and chronic paroxysmal hemicrania were not
      modified by polysomnography. The migraine and tension headache groups had a
      relative male preponderance, and the diagnosis was changed in approximately half
      of the patients. This was also observed in combined headaches. Patients who had
      chronic substance abuse headaches had mainly insomnia, which in some cases, was
      relieved by stopping medication. Data were also analyzed in terms of simple
      models linking headache and sleep disturbances. Such an approach allowed the
      identification of several modes of mutual interaction. In summary, morning or
      nocturnal headaches are frequent indicators of a sleep disturbance and their
      presence might justify polysomnography, and the use of simple clinical models may
      be useful for understanding the complex relationship between headache and sleep.

PMID- 8550360
TI  - Intravenous magnesium sulfate relieves cluster headaches in patients with low
      serum ionized magnesium levels.
AB  - Patients with cluster headaches have been reported to have low serum ionized
      magnesium levels. We examined the possibility that patients with cluster
      headaches and low ionized magnesium levels may respond to an intravenous infusion
      of magnesium sulfate. Thirty-eight infusions of magnesium sulfate were given to
      22 patients with cluster headaches. The mean ionized magnesium level prior to 23
      infusions which provided relief for at least 2 days and enabled the patient to
      skip two or more attacks, was 0.521 +/- 0.016 mmol/L; this value was 0.561 +/-
      0.016 prior to 15 infusions which were ineffective. These latter 15 infusions
      were preceded by higher total magnesium levels. The ionized magnesium level prior
      to the 23 effective infusions was below 0.54 mmol/L in 19 patients. Five of the
      15 ineffective infusions were accompanied by basal ionized magnesium levels below
      0.54 mmol/L. In 76% of the infusions, there was a correlation between a response
      and an ionized magnesium level below 0.54 mmol/L. Nine patients (41%) obtained
      clinically meaningful improvement. Spontaneous remissions and a placebo effect
      might have accounted for some of the improvement. However, this should have
      applied equally to all patients, regardless of the ionized magnesium level.
      Measurements of ionized magnesium may prove useful in elucidating the
      pathogenesis of cluster headache and in identifying patients who may benefit from
      treatment with magnesium.

PMID- 8550361
TI  - Long-term efficacy of subcutaneous sumatriptan using a novel self-injector.
AB  - An open, multicenter study investigated the long-term efficacy, tolerability, and
      acceptability to patients of subcutaneous sumatriptan 6 mg, administered using a
      novel cartridge system self-injector, for the acute treatment of migraine. Eighty
      patients treated all migraine attacks for 6 months at home with a subcutaneous
      injection of sumatriptan 6 mg. A second injection could be taken after 1 to 24
      hours if relief was inadequate, or if the headache recurred, and rescue
      medication could be taken 1 hour after the second injection. The primary end
      point was the percentage of attacks in which headache improved from severe or
      moderate before treatment to mild or absent at 1 hour after the first injection.
      A total of 1566 attacks were treated by the 80 patients and 69 patients completed
      6 months of treatment. Headache relief was reported 1 hour after the first
      injection in a mean of 78% of attacks (83% in the first 3 months and 76% in the
      second 3 months). A second injection was required in a mean of 40% of attacks,
      and headache was mild or absent 1 hour after the second injection in a mean of
      77% of attacks. Rescue medication was required after the second injection in a
      mean of 14% of attacks. At the end of the study, 87% of patients said that they
      would take the medication again, and at each clinic visit over 80% said that they
      found the injector easy to use. Adverse events were similar to those reported
      previously with sumatriptan and were mostly mild to moderate in intensity, short
      lived, and resolved spontaneously. Subcutaneous sumatriptan 6 mg is an effective,
      well tolerated, and well accepted, long-term, acute treatment for migraine when
      self-injected by patients using the novel self-injector.

PMID- 8550362
TI  - Preemptive oral treatment with sumatriptan during a cluster period.
AB  - This multinational, multicenter, randomized, double-blind, placebo-controlled
      study in 169 patients investigated the effect of a 7-day period of preemptive
      treatment with oral sumatriptan (100 mg tid) on the frequency and severity of
      cluster headache attacks occurring during an established cluster headache period.
      Safety and tolerability were also assessed. Cluster headache patients who were
      not taking prophylactic medication and had experienced seven or more attacks in
      the preceding observation week, treated a cluster headache attack at home with
      subcutaneous sumatriptan 6 mg using an autoinjector device. Patients were then
      randomized to take sumatriptan 100 mg or placebo at 8-hourly intervals for a 7
      day period. Cluster headaches occurring during this period could be treated 5
      minutes after onset with rescue medication (100% oxygen or simple analgesics).
      Diary cards were used to record details of the cluster headache pattern during
      the observation and study treatment weeks. Preemptive oral treatment with
      sumatriptan 100 mg tid for 7 days did not produce a significant reduction in the
      number or severity of cluster headache attacks occurring during an established
      cluster headache period. Oral treatment with sumatriptan 100 mg tid over a 7-day
      period was not associated with an increased or altered adverse event profile from
      that previously reported.

PMID- 8550363
TI  - Oculocephalic sympathetic dysfunction in posttraumatic headaches.
AB  - Oculocephalic sympathetic functions were assessed in five patients with
      posttraumatic headaches using the thermoregulatory sweat test and biochemical
      pupillary responses. Four patients demonstrated bilateral sympathetic dysfunction
      following whiplash injury, and one patient demonstrated unilateral sympathetic
      dysfunction following forehead injury. Biochemical pupillary responses were
      diagnostic in the early posttraumatic period, while the thermoregulatory sweat
      test was abnormal up to 56 months following the injury. This study documents
      serious injury to the cervical sympathetic nerves in patients with posttraumatic
      headaches following whiplash injury, and shows the reliability of the
      thermoregulatory sweat test in identifying patients with long-term oculocephalic
      sympathetic dysfunction. It also shows dissociated postganglionic cranial
      sympathetic dysfunction. Our experience and a review of the pertinent literature
      shows no convincing clinical or experimental evidence to establish oculocephalic
      sympathetic dysfunction as a direct cause of head pain, but it may exert an
      effect on cephalic pain through the trigeminovascular system.

PMID- 8550364
TI  - Characteristics of patients successfully treated for cervicogenic headache by
      surgical decompression of the second cervical root.
AB  - We have recently reported 90% success in a series of patients undergoing
      microsurgical decompression of the second cervical (C2) nerve root and ganglion
      for cervicogenic headache. Review and analysis of our database was carried out in
      order to cull factors characterizing patients amenable to this surgical
      treatment. Thirty-five sequential C2 decompressions performed on 31 patients who
      were pain-free or significantly improved in follow-up were evaluated
      retrospectively. Preoperative factors and intraoperative findings were analyzed
      for prognostic significance. The diagnosis of cervicogenic headache was made
      using established criteria and success of CT-guided C2 anesthetic blockade in
      alleviating the headache. Numerous historical factors noted preoperatively
      including age, sex, history of trauma, autonomic symptoms, visual changes, and
      many others were not able to be well correlated with outcome in univariate
      analysis. Likewise, no strong correlation could be made for findings on physical
      examination. Thus, no specific prognostic factors could be established, other
      than the accepted diagnostic criteria and successful anesthetic blockade of the
      C2 root and ganglion. These factors should identify the subset of patients with
      cervicogenic headache predominantly due to C2 root or ganglion effect and thus
      may favor a surgical treatment.

PMID- 8550365
TI  - Responders and nonresponders to autogenic training and cognitive self-hypnosis:
      prediction of short- and long-term success in tension-type headache patients.
AB  - The present study was conducted to determine whether demographic variables,
      medical status variables, and psychological measures at pretreatment were related
      to pain reduction immediately following behavioral treatment for headache and at
      a 6-month follow-up. The study sample consisted of 156 subjects, who were
      selected for participation in a behavioral outcome study on the efficacy of
      autogenic training and cognitive self-hypnosis training. A Headache Index based
      on pain diaries constituted the main outcome measure. Psychological measures
      included the Symptom Checklist-90, Dutch Personality Questionnaire, Coping
      Strategy Questionnaire, Multidimensional Locus of Pain Control Questionnaire, and
      treatment expectations. Subjects who expected more pain reduction at pretreatment
      achieved a lower level of pain at posttreatment, independent of pretreatment pain
      levels. None of the other pretreatment variables were related with pain reduction
      at posttreatment or at the follow-up. Finally, at the 6-month follow-up, 43
      subjects were classified as responders (more than 50% pain reduction) and 113 as
      nonresponders (less than 50% pain reduction and dropouts). At pretreatment, the
      responders perceived more pain control than the nonresponders. None of the other
      pretreatment differences between responders and nonresponders proved to be
      significant. The main conclusion that could be drawn from this study was that
      pain reduction, in the short- and long-term, cannot be predicted with any
      accuracy by demographic and medical status variables or scores for psychological
      distress, personality traits, coping strategy use, and pain appraisals.

PMID- 8550366
TI  - Dihydroergotamine and metoclopramide in the treatment of organic headache.
AB  - Dihydroergotamine and metoclopramide have been used in the treatment of benign
      headache for many years. The presumed mechanism of action of dihydroergotamine
      and metoclopramide is related to these drugs' affinity for serotonergic
      receptors. We present three cases of the use of dihydroergotamine and
      metoclopramide in patients with organic headache (two patients with viral
      meningitis and one patient with meningeal carcinomatosis). All three patients had
      excellent symptomatic relief. Our results demonstrate that dihydroergotamine and
      metoclopramide can be effective in treating organic headache and, therefore,
      symptomatic relief can not be assumed to signify benign disease.

PMID- 8550367
TI  - Headache following removal of acoustic neuroma.

PMID- 8550368
TI  - Community mobilization to reduce point-of-purchase advertising of tobacco
      products.
AB  - This project was designed to address the problem of point-of-purchase tobacco
      advertising through media advocacy and community mobilization. Precampaign
      assessment revealed a considerable amount and density of tobacco advertising and
      promotions in more than 100 stores sampled in San Jose, California. After sharing
      the results with community activists and other residents, a community
      mobilization campaign was instigated to capitalize on an existing sign control
      ordinance that limits store window coverage and sidewalk signs. Through
      presentations and media advocacy efforts, community residents were mobilized to
      file complaints with the city's code enforcement office when neighborhood stores
      were shown to be noncompliant with ordinance provisions. Relative to the
      baseline, significant reductions in campaign-related tobacco advertising
      variables were seen in the San Jose stores after the sign law campaign. No
      changes were seen in four smaller reference communities. Differences were noted
      between stores close to and farther away from schools. These results demonstrate
      that mobilization of community residents to activate enforcement of laws
      originally designed for other purposes can have a significant impact on one
      aspect of tobacco point-of-purchase advertising.

PMID- 8550369
TI  - Mobilizing a low-income African-American community around tobacco control: a
      force field analysis.
AB  - A statewide tobacco control campaign in California has been highly successful in
      reducing public exposure to the health hazards of secondhand smoke. Over 250
      cities and counties in California have enacted local ordinances to regulate
      smoking in public places and workplaces. Although low-income people of color are
      disproportionately affected by the use of tobacco, the issue of regulating
      secondhand smoke tends to be a lower priority in communities that are confronted
      by other, more immediately pressing social justice issues, such as high rates of
      violence and lack of economic opportunity. This article describes the process
      undertaken by a county health department to mobilize a low-income African
      American community in a San Francisco Bay Area city to support a local ordinance
      mandating 100% smoke-free workplaces and restaurants. These efforts are more
      likely to succeed if health advocates (1) reframe issues in a context that
      acknowledges the political, economic, and social justice realities and strengths
      of the community; (2) organize within existing local networks and foster the
      integration of tobacco issues into the group's existing work; and (3) can defer
      their own agendas during times of community grieving and healing.

PMID- 8550370
TI  - Combining research, advocacy, and education: the methods of the Grandparent
      Caregiver Study.
AB  - This article presents a case study of the effective synergy of health education
      inquiry, community collaboration, and policy advocacy. Using the Grandparent
      Caregiver Study as the example, the authors focus on key methodological decisions
      that enabled them to incorporate research, education, and advocacy activities
      into an ever-growing project on a modest budget. The study itself centered on two
      in-depth interviews with each of 71 African American grandmothers raising young
      grandchildren due to the crack cocaine epidemic in Oakland, California. The case
      study demonstrates ways in which health education research can increase the
      efficacy of individuals and disenfranchised groups to define problems, voice
      their concerns, and advocate for more just and healthy public policies. Through
      discussion of the authors' methods and activities, they suggest strategies
      through which research participants, service providers, and policymakers can work
      together to bring a new issue to the policy arena through a collaborative and
      empowering research process.

PMID- 8550371
TI  - Policy and environmental interventions for the prevention and control of
      cardiovascular diseases.

PMID- 8550372
TI  - Environmental and policy interventions to control tobacco use and prevent
      cardiovascular disease.
AB  - Despite its declining prevalence during the past few decades, tobacco use remains
      one of the most significant public health issues of the 1990s. Environmental and
      policy interventions are among the most cost-effective approaches to control
      tobacco use and prevent cardiovascular diseases. In this article, the authors
      review and offer to state and local health departments and other public health
      partners a summary of recommended policy and environmental interventions that
      have either reduced or show potential to reduce tobacco use. Priority
      recommendations include clean indoor air policies, restrictions on tobacco
      advertising and promotion, policies limiting youth access to tobacco,
      comprehensive school health programs, and excise taxes and other economic
      incentives. Many of these recommendations should be integrated with other health
      promotion interventions to also improve nutrition and physical activity. The
      authors also highlight several successful interventions and strategies used to
      establish policies at the state and local levels.

PMID- 8550373
TI  - Environmental and policy approaches to cardiovascular disease prevention through
      physical activity: issues and opportunities.
AB  - The majority of Americans remain inactive despite evidence of significant health
      benefits from even moderately intense activity. Previous intervention efforts
      have generally focused on changing individual behavior. This article discusses
      the use of policy, legislative and regulatory, and environmental interventions in
      promoting physical activity to prevent cardiovascular disease (CVD) and other
      chronic diseases. The authors present evidence on the need, formulation,
      description, and effectiveness of policy and environmental intervention
      approaches. Types of approaches addressed to promote physical activity include
      federal, state, and local legislation and regulation, policy development and
      implementation, and environmental support. They also describe opportunities for
      state and local health departments to initiate and participate in environmental
      and policy approaches.

PMID- 8550374
TI  - Environmental and policy approaches to cardiovascular disease prevention through
      nutrition: opportunities for state and local action.
AB  - This article reviews environmental and policy intervention approaches to
      cardiovascular disease prevention through nutrition and recommends opportunities
      for state and local health departments to initiate and participate in
      environmental and nutrition policy initiatives. By addressing these complementary
      aims, the authors hope to stimulate further efforts to achieve progress in
      nutrition promotion among state and local health-related organizations. Key
      categories of opportunity to develop new or expanded nutrition policies and
      environmental strategies include economic incentives, food assistance and feeding
      programs, regulations for institutional food service operations, and nutrition
      services in health care. Environmental strategies to reduce barriers to following
      dietary guidelines, such as point-of-choice programs and school nutrition
      programs, should be tailored for local communities and widely disseminated. In
      addition, current federal policy efforts, notably nutrition labeling rules, will
      provide a valuable focal point for state and local advocacy, education, and
      monitoring.

PMID- 8550375
TI  - In situ localization with digoxigenin-labelled probes of tau-related mRNAs in the
      rat pancreas.
AB  - Two cDNA probes complementary to fetal rat brain tau cDNA were produced by the
      polymerase chain reaction (PCR) and labelled by digoxigenin-11-dUTP incorporation
      during the PCR elongation step. These probes were tested for the in situ
      localization of tau mRNAs in sections of rat cerebellum. The hybridization signal
      was consistent with the known localization of brain tau mRNAs, showing the
      validity of cDNA probes labelled by digoxigenin during the PCR. Using these
      probes, an in situ hybridization protocol was established and optimized for the
      localization of tau-related mRNAs in sections of pancreas. The aim was to
      determine whether these mRNAs were expressed in the exocrine or the endocrine
      part of the pancreas. A positive signal was found only in the exocrine part of
      the pancreas, and was distributed exclusively in the cytoplasm of acinar cells.
      The results described here are the first evidence for a specific expression of
      tau-related proteins in the exocrine pancreas.

PMID- 8550376
TI  - Immunohistochemical localization of antioxidant enzymes during hamster kidney
      development.
AB  - Immunolocalization studies of hamster kidney development were performed using
      polyclonal antibodies to antioxidant enzymes, including antibodies to copper,
      zinc and manganese superoxide dismutases, catalase, glutathione peroxidase and
      glutathione S-transferases and their subunits. Antibodies to extracellular matrix
      proteins were also studied to determine the temporal sequence between expression
      of immunoreactive protein for basement membrane proteins, which serve as markers
      of embryonic induction of nephron development, and antioxidant enzyme expression
      in kidney development. Immunoreactive proteins for antioxidant enzymes were not
      detectable in the developing kidney until after extracellular matrix proteins had
      been deposited. However, immunoreactive proteins for the antioxidant enzymes
      copper, zinc and manganese superoxide dismutases, catalase, and alpha class
      glutathione S-transferase Ya subunit were detected in renal tubules before birth.
      mu class glutathione S-transferase subunits Yb1 and Yb2 stained transitional
      epithelium at high levels before birth. Our results indicate: (1) each type of
      kidney cell has a unique antioxidant enzyme profile, (2) antioxidant enzymes are
      expressed in different types of cell at different times during development, but
      antioxidant enzyme immunoreactive protein was not present until after
      immunoreactive proteins for extracellular matrix molecules were detected, and (3)
      certain antioxidant enzymes are present before birth, indicating that high oxygen
      tension present at birth is not crucial for induction of immunoreactive protein.

PMID- 8550377
TI  - Carbonic anhydrase is present in human oesophageal epithelium and submucosal
      glands.
AB  - Carbonic anhydrase (EC 4.2.1.1) activity was investigated in normal human
      oesophageal mucosa using the Hansson and Ridderstrale catalytic cobalt methods.
      The enzyme was detected in the cell membranes and nuclei and, to a lesser extent,
      in the cytoplasm of the epithelial cells of the mucosa giving a 'chicken wire'
      appearance. Activity decreased towards the lumen. Other stratified squamous
      epithelia--buccal mucosa, ectocervix and skin--gave a similar pattern. Acinar
      cells of oesophageal submucosal glands also exhibited activity for the enzyme,
      but the ducts did not. The formation of reaction product was prevented by
      acetazolamide and ethoxzolamide and by the omission of bicarbonate frm the
      substrate medium. Carbonic anhydrase in oesophageal squamous epithelium may be
      involved in the control of intra- and extracellular pH, while that in the glands
      is more likely to be concerned with bicarbonate secretion.

PMID- 8550378
TI  - Lysosomal origin of the chloragosomes in the chloragogenous tissue of the
      earthworm Eisenia foetida: cytochemical demonstration of acid phosphatase
      activity.
AB  - The cytochemical localization of the lysosomal marker enzyme acid phosphatase was
      studied in the chloragogenous tissue of earthworms. The Gomori lead technique and
      the cerium capture technique were utilized. Both techniques demonstrated the
      chloragosomal location of this enzyme. Only a small proportion of chloragosomes
      presented reactivity, which suggests that these organelles are distinctly
      heterogeneous. The reaction product was localized in the periphery of
      chloragosomes, suggesting a membrane-bound compartmentalization of acid
      phosphatase. In addition, degenerating mitochondria and membrane whorls were
      observed in some chloragosomes, indicating the possibility that these organelles
      perform autophagosomal functions.

PMID- 8550379
TI  - Evidence for the presence of immunoreactive POMC-derived peptides and cytokines
      in the thymus of the goldfish (Carassius c. auratus).
AB  - The presence of immunoreactive pro-opiomelanocortin (POMC)-derived peptides
      (adrenocorticotropin hormone, beta-endorphin, alpha-melanocyte-stimulating
      hormone) and of cytokine-like molecules [interleukin (I)-1 alpha, IL-1 beta, IL
      2, Il-6, tumour necrosis factor-alpha] was demonstrated in periodic acid-Schiff
      positive epithelial cells in the thymus of the goldfish (Carassius c. auratus)
      using immunocytochemical procedures. POMC-derived peptide- and cytokine-like
      molecules were localized in the same cell type. Lymphocytes were negative for all
      the above mentioned molecules. Despite the smaller number of cells positive for
      neuropeptide- and cytokine-like molecules, our findings suggest that immune
      neuroendocrine interactions are likely to occur in the thymus of goldfish.

PMID- 8550380
TI  - Basal lamina formation by porcine thyroid cells grown in collagen- and laminin
      deficient medium.
AB  - Porcine thyroid cells isolated by dispase treatment were cultured in either (a)
      Matrigel, (b) agarose with the addition of different combinations of basic
      fibroblast growth factor and laminin, or (c) on agarose-coated dishes. The
      formation of follicles and the presence of a basal lamina was investigated by
      routine electron microscopy of Araldite-embedded material and by light and
      electron microscopical immunocytochemical detection of the basal lamina
      components, laminin and collagen type IV. After 10 days of culture in Matrigel or
      agarose, a basal lamina-like structure surrounded most follicles. Follicles of
      cells growing in agarose and overlaid with a medium containing thyrotropin and
      overlaid with a medium containing thyrotropin and fibroblast growth factor showed
      a fluorescent band at the basal side of the follicles after immunocytochemical
      staining with anti-laminin and anti-collagen antibodies. Routine electron
      microscopy showed that a basal lamina-like structure lined the outside of the
      follicle. This structure could be subdivided into a lamina lucida and a lamina
      densa. Electron microscopical immunogold labelling revealed that immunologically
      detectable laminin was confined to the lamina densa. These findings suggest that
      even in the absence of basal lamina components in the culture medium, thyroid
      cells are able to form follicles with a regular basal lamina when they are
      cultured in a three-dimensional environment.

PMID- 8550381
TI  - Electron microscopical study of a cytosolic enzyme in unfixed cryostat sections:
      demonstration of glycogen phosphorylase activity in rat liver and heart tissue.
AB  - Glycogen phosphorylase activity has been demonstrated at the ultrastructural
      level in liver and heart tissue of fasted rats. Unfixed cryostat sections were
      incubated by mounting them on a semipermeable membrane stretched over a gelled
      incubation medium. The medium contained a high concentration of glucose 1
      phosphate which enables indirect detection of glycogen phosphorylase activity on
      the basis of the synthesis of glycogen. Tissue fixation, dehydration and
      embedding for electron microscopical study were performed after the incubation
      had been completed. The ultrastructure of both liver and heart tissue was rather
      well preserved. Glycogen granules resulting from glycogen phosphorylase activity
      were found in the cytoplasmic matrix of both hepatocytes and cardiomyocytes; no
      relationship with membranous structures could be detected. It is concluded that
      the semipermeable membrane method is well suited for localizing cytosolic enzyme
      activities at the ultrastructural level without prior tissue fixation; this opens
      further perspectives for correlations between histochemical and biochemical data.

PMID- 8550382
TI  - Effects of fixation on the preservation of peroxisomal structures for
      immunofluorescence studies using HepG2 cells as a model system.
AB  - The immunofluorescence technique has become an important tool for the
      investigation of peroxisomes in cell culture. We have used this method for the
      study of peroxisomes in the human hepatoblastoma cell line HepG2. A marked
      heterogeneity of peroxisomal forms was detected. Besides spherical (about 100 nm)
      and rod-shaped structures (about 300 nm) many elongated, undulating tubular forms
      (up to 5 microns) were found. Further observations indicate that the appearance
      of the peroxisomal forms in immunofluorescence is dependent on the fixation
      procedure used. Whereas the fixation with methanol-acetone (-20 degrees C) or
      ethanol results in a punctate pattern with spherical particles, the use of
      formaldehyde/Triton X-100 fixation shows well-preserved tubules and rods. These
      observations may be of special importance for studies on the biogenesis of
      peroxisomes.

PMID- 8550383
TI  - Histochemical demonstration of different types of poly-N-acetyllactosamine
      structures in human thyroid neoplasms using lectins and endo-beta-galactosidase
      digestion.
AB  - Blood-group-related antigens expressed in papillary carcinomas and other types of
      neoplasm of the human thyroid glands have been shown to be carried by poly-N
      acetyllactosamines containing a linear domain susceptible to endo-beta
      galactosidase digestion. To make clear more precisely the backbone poly-N
      acetyllactosamine structures, labelled lectins specific to different types of
      these structures and specific to core structures with beta 1-6GlcNAc branching of
      N- and O-linked glycoproteins were employed in conjunction with prior endo-beta
      galactosidase digestion on formalin-fixed, paraffin-embedded neoplasms of the
      human thyroid glands. In papillary carcinomas, Datura stramonium agglutinin (DSA)
      and succinyl wheat germ agglutinin (Suc-WGA) reacted most consistently and
      frequently with papillary carcinomas from all the individuals examined. Pokeweed
      mitogen (PWM) likewise stained the cells of papillary carcinomas from all the
      individuals examined, but in some individuals the number of lectin-reactive cells
      were very small. Lycoperscion esculentum aggultinin (LEA), Solanum tuberosum
      agglutinin (STA), Phaseolus vulgaris agglutinin L (PHA-L) and Artocarpus
      integrifolia agglutinin (jacalin) similarly bound to the cancer cells from most
      of the individuals, and in these cases the number of reactive cells was usually
      much more restricted than was the case with DSA or PWM. In adenoma and other
      types of carcinoma, such as follicular carcinomas, these lectins specific to poly
      N-acetyllactosamine exhibited slight or no reactivity with the cells, whereas PHA
      L and jacalin similarly bound to the cells of adenomas and carcinomas from most
      of the individuals examined. Prior digestion with endo-beta-galactosidase
      completely eliminated or markedly reduced the reactivity with PWM and LEA in
      papillary carcinomas. Reactivity with DSA, Suc-WGA, STA, PHA-L and jacalin was
      slightly reduced or not at all affected by enzyme digestion. These results
      confirmed that poly-N-acetyllactosamine species found in papillary carcinomas are
      quite different from those in other types of thyroid neoplasm, suggesting that at
      least three different types of poly-N-acetyllactosamine, that is, linear
      unbranched short and long sequences and highly branched ones are produced in
      these cells.

PMID- 8550384
TI  - Carbohydrate and peptide antigens in macrophage populations derived from human
      bone marrow and milk: an immunomorphological and immunochemical analysis.
AB  - An immunomorphological and immunochemical study was performed to elucidate the
      pattern of carbohydrate antigens and their relationships to the cluster
      differentiation (CD) 68 epitopes on macrophages derived from human bone marrow
      and milk. Core and backbone antigens recognized by lectins from Bauhinia purpurea
      (BPA), Helix pomatia (HPA), Arachis hypogaea (PNA), Glycine max. (SBA), Griffonia
      simplicifolia (GSA-I-B4), Lycopersicon esculentum (LEA) and Erythrina cristagalli
      (ECA) were expressed by both macrophage populations. Additionally, they exhibited
      various peripheral type 1 and type 2 carbohydrate antigens. In bone marrow
      trephine biopsies, the number of macrophages stained by the CD68-specific
      monoclonal antibody PG-M1 exceeded significantly (range 30-40%) the subpopulation
      expressing SBA, GSA-I-B4, and ECA binding sites as well as the Lewisa antigen.
      This result is very interesting since, from in vitro studies GSA-I-B4 and SBA are
      known to react especially with activated macrophages. Western blotting
      experiments on milk macrophage lysates revealed that ECA, GSA-I-B4, BPA, PNA and
      MAA visualize a 110 kDa band isographic with the CD68 antigen detected by PG-M1,
      KP1 and Ki-M1P monoclonal antibodies. These antibodies recognize peptide epitopes
      as shown by enzyme-linked immunosorbent assays after biochemical modification of
      milk macrophage lysates. This result is in keeping with the assumption that the
      CD68 antigen consists of a highly glycosylated mucin-type glycoprotein comprising
      various differentiation-dependent epitopes.

PMID- 8550385
TI  - A biochemical and immunocytochemical study on the targeting of alglucerase in
      murine liver.
AB  - A current hypothesis is that functional glucocerebrosidase needs to be delivered
      to the lysosomes of tissue macrophages to guarantee successful enzyme therapy for
      Gaucher's disease. In this study, biochemical and immunohistochemical techniques
      were applied to identify in mice the localization of intravenously administered
      alglucerase (human modified placental glucocerebrosidase). Only in liver and
      spleen was a significant increase of glucocerebrosidase activity observed, with a
      maximum level at 15 minutes after enzyme infusion. The uptake of enzyme by liver
      was sufficiently high to allow more detailed studies on the (sub)cellular
      distribution of human alglucerase. The enzyme in liver is localized both in the
      endosomal-lysosomal system of the Kupffer cells and the endothelial cells lining
      the lumen of the sinusoids. Uptake by both of these types of cell is prevented by
      mannan. The results suggest that the cellular mechanisms responsible for
      improvement of Gaucher patients receiving alglucerase treatment is probably more
      complicated than previously recognized.

PMID- 8550386
TI  - Embolization of bleeding gastroduodenal pseudoaneurysm in pancreatitis.
AB  - A case of successful wire coil embolization of a bleeding gastroduodenal
      pseudoaneurysm secondary to necrotizing pancreatitis with pseudocyst formation is
      reported. The embolization technique using multiple coils is discussed and
      compared with other techniques previously described.

PMID- 8550387
TI  - Hand and foot acrometastases in a patient with bronchial carcinoma.
AB  - The occurrence of acrometastases in a patient with bronchial carcinoma is rare
      but well known. Lung tumours however seldom give rise to foot metastases. The
      simultaneous occurrence of both hand and foot metastases in the same patient is
      extremely rare. We describe a patient with epidermoid epithelioma of the lung who
      developed such lesions as the first manifestation of metastatic disease.

PMID- 8550388
TI  - A rare cause of rickets in a young child.
AB  - We present a case of nutritional rickets in a young child due to a macrobiotic
      diet. The child presented with important thoracic deformation and breathing
      difficulties. Plain radiographs appeared to be an excellent method for the
      diagnosis and follow-up of the bony lesions in this disorder. We describe the
      typical bony abnormalities related to this relative rare disease.

PMID- 8550389
TI  - The beginning of radiology in Belgium.
AB  - It is quite difficult to determine who produced the first "cathodographs" in
      Belgium. As soon as the news of the discovery spread in Belgium, numerous Belgian
      laboratories repeated, and even improved, Rontgen's experiments. Scientists who
      made important contributions include J.D. Lucas, J. Thirion, W. van Havre, F.
      Dwelshauvers-Dery, F. Richard, Van Duyse and J. De Nobele, Herthoge, Th. Dineur,
      A. Bienfait, L. Lejeune, and J. Maffei ...

PMID- 8550390
TI  - [Stereoradiography].
AB  - The first attempts at stereography date back to the early days of radiography
      itself; already at the turn of the century, a series of papers on this subject
      had been published. This is not surprising, as the problem of reading correctly a
      plain X-ray film was rapidly recognized. A plain X-ray film is a summation of all
      the more or less opaque structures contained in the different planes of an
      object. Stereoradiography not any copes with this problem, but enables a three
      dimensional localization of all these structures. Stereofluorography and
      stereocineradiography may also be performed. The different stages in the
      development of hard and soft ware to achieve these goals are described and an
      example is provided.

PMID- 8550392
TI  - [The history of gallbladder and bile duct diagnosis].
AB  - In the first period (1896-1910), investigation was made through plain abdominal
      film with description and differential diagnosis of the different calcifications
      in the right hypochondrium. Second period (1911-1924): indirect signs of liver
      and gallbladder pathology were described. Via pneumoperitoneum and gastro
      intestinal opacification the pathology in the right hypochondrium was delineated
      and interpreted. Third period (1924 until now): due to the development of
      contrast agents for the gallbladder and biliary tree, these organs could be
      directly visualized either by intravenous injection, or by peroral
      administration; sometimes direct injection of contrast in the bile ducts was
      used.

PMID- 8550391
TI  - [The history of tomography].
AB  - It is easily forgotten that not yet a hundred years ago the only way to look into
      the patients' body was via invasive procedures. Within the year of the discovery
      of X-rays by Conrad Rontgen the need for three dimensional imaging had been
      voiced. The driving force behind this development was undoubtedly clinical
      motivation. Planar X-radiographs were not satisfactory to the clinicians who
      urged the radiologists to provide them with tomographic images. Between 1910 and
      1940, classical tomography has been the product of individuals rather than
      collective groups. It is only in the mid thirties that scientists found out about
      each other and started to correspond vigorously. Mayer was the first to suggest
      in 1914 the idea of tomography. Bocage, Grossman and Vallebona all developed the
      idea further and built their own equipment. In 1931 Ziedses des Plantes published
      the most extensive and thorough study on tomography. In the forties and fifties a
      stagnation is noticed, only further refinements to the existing equipment are
      carried out. Although Frank and Takahashi published the basic principles of axial
      tomography in the mid forties, we had to wait for the necessary developments in
      electronics before Hounsfield was able to develop and commercialize the first
      axial computer tomography in 1972 (EMI-Scanner). At the time all the big
      radiology companies rushed into the field and soon, second, third and fourth
      generation CT scanners became available. Only a few years later a new way of
      generating images without using ionizing radiation was introduced. Lauterbur and
      Damadian produced the first low quality images with magnetic resonance, a
      technique called zeugmatography by its inventors. In 1974 the first images of a
      living subject were published and initial scepticism was replaced by euphoria.
      This resulted in the spectacular evolution in Magnetic Resonance that we are now
      observing. While it is impossible to predict the future, the development of
      networks, the increase in data acquisition and storage will spread a new light on
      our specialty. A closer cooperation between radiologists, pathologists and
      clinicians will undoubtedly be necessary, as well as a partial redefinition of
      the radiologists task.

PMID- 8550393
TI  - The history of uroradiology.
AB  - In the first period (1896-1910), investigation was made through plain abdominal
      film with description and differential diagnosis of the different calcifications
      in the right hypochondrium. Second period (1911-1924): indirect signs of liver
      and gallbladder pathology were described. Via pneumoperitoneum and gastro
      intestinal opacification the pathology in the right hypochondrium was delineated
      and interpreted. Third period (1924 until now): due to the development of
      contrast agents for the gallbladder and biliary tree, these organs could be
      directly visualized either by intravenous injection, or by peroral
      administration; sometimes direct injection of contrast in the bile ducts was
      used.

PMID- 8550394
TI  - [Radiodiagnosis in obstetrics and gynecology].
AB  - Immediately after Rontgen's discovery, people started trying to find uses for the
      new rays in gynecology and obstetrics. Although the first reports date from 1896
      97, even in the 1920's there were textbooks to be found without any mention of
      the use of radiology in both areas of medicine. The availability of reliable
      contrast media led to the development of new imaging techniques and to the golden
      age of obstetrical and gynecological radiology in the 1930-1970 period. Nowadays
      ultrasound has replaced most conventional techniques while MRI is becoming more
      and more important. A historical overview of the different radiological
      techniques is provided.

PMID- 8550395
TI  - [Cardiac radiology].
AB  - From the beginning of the era of X-rays, cardiac radiology has become a target of
      this new technique. Early pioneers, Ciegem, Rieder, Rosenthal, Williams rapidly
      accumulated extensive experience with fluoroscopy and radiography and
      publications on cardiac diseases as soon as 1899 and 1901 and 1902. The next step
      in cardiac diagnosis was achieved by Forsmann in 1929, with the first attempt at
      cardiac catheterization and angiocardiography. Many clinicians, Moniz, Reboul,
      Rousthoi contributed to the development of the technique between 1930 and 1940. A
      further turning point came in 1941 when Cournand demonstrated that cardiac
      catheterization was a safe method in man. In the technical field major progress
      came from Scandinavia were rapid filming was born. The management of ischaemic
      disease, changed dramatically with the demonstration of coronary anatomy, largely
      due to Sones, Judkins and Amplatz. A further progress was initiated in 1977 by
      Gruentzig who invented balloon angioplasty.

PMID- 8550397
TI  - Radiology has a future!

PMID- 8550396
TI  - The history of angiography.
AB  - From the beginning of the era of X-rays, cardiac radiology has become a target of
      this new technique. Early pioneers, Ciegem, Rieder, Rosenthal, Williams rapidly
      accumulated extensive experience with fluoroscopy and radiography and
      publications on cardiac diseases as soon as 1899 and 1901 and 1902. The next step
      in cardiac diagnosis was achieved by Forsmann in 1929, with the first attempt at
      cardiac catheterization and angiocardiography. Many clinicians, Moniz, Reboul,
      Rousthoi contributed to the development of the technique between 1930 and 1940. A
      further turning point came in 1941 when Cournand demonstrated that cardiac
      catheterization was a safe method in man. In the technical field major progress
      came from Scandinavia were rapid filming was born. The management of ischaemic
      disease, changed dramatically with the demonstration of coronary anatomy, largely
      due to Sones, Judkins and Amplatz. A further progress was initiated in 1977 by
      Gruentzig who invented balloon angioplasty.

PMID- 8550398
TI  - MR in the evaluation of gynecologic tumor.
AB  - MR imaging has proved value in the study of the female pelvis. In the past five
      years numerous reports from all over the world have testified to the superiority
      of MR imaging over Ultrasound (US) and Computed Tomography (CT) in the assessment
      of a wide range of conditions, including congenital abnormalities, benign or
      malignant tumors, and obstetrics. MR imaging should not only be used as a problem
      solving modality, but also should have an immediate impact on treatment
      alternatives. Furthermore, the continuing advances in MR Imaging (e.g.
      development of new pulse sequences and surface coils) have imposed further
      demands on radiologists to familiarize with the current state of MR imaging. This
      article reviews the advantages, limitations, and unknown factors of some aspects
      of MR imaging of tumors in the female pelvis, including the use of contrast
      media, fast spin echo-imaging and surface coils.

PMID- 8550399
TI  - [Three-dimensional imaging of acetabular fractures using spiral CT].
AB  - Seven adult patients with acetabular fractures were investigated with
      conventional X-rays, axial spiral computed tomographic (CT) images and three
      dimensional (3D) surface rendered reconstructions. Spiral CT has the advantage
      that it acquires the data much faster than incremental CT, resulting in less
      motion artefacts. A semi-automatic three-dimensional environment for segmentation
      has been developed in our institution. It created significant reduction of user
      interaction and improved visualization of acetabular and femoral joint surfaces.
      The main advantages of three-dimensional visualization of acetabular fractures
      included: creation of unlimited and unique views by which fracture location,
      fracture extension, fragment shape and fragment position became more clear,
      better visualization of acetabular dome and quadrilateral plate and more simple
      and easier interpretation of these complex fracture patterns. On the other hand,
      3D surface reconstructions do not accurately demonstrate undisplaced fractures,
      intra-articular fragments may be obscured, congruence assessment is uneasy, and
      soft tissue injuries are not shown. Therefore, we consider 3D images of
      acetabular fractures as being complementary to and not a substitute to plain
      radiographs and axial CT scans.

PMID- 8550400
TI  - Technical quality control in mammography screening: first results in Belgium.
AB  - In this paper the first results of the application in Belgium of the European
      protocol for the technical quality control of mammography screening are
      presented. Twelve mammography screening units were submitted to an acceptance
      test: one fourth complied with the criteria after a second visit. A daily quality
      control procedure has been run since eighteen months. The most important detected
      problems are given and discussed. The European Commission, in the framework of
      "Europe Against Cancer", recently published the "European Guidelines for Quality
      Assurance in Mammography Screening" (1). In another contribution (2), a brief
      overview of the important appendix "European Protocol for the Quality Control of
      the Technical Aspects of Mammography Screening" was given. In this paper the
      first results for the application of this protocol in Belgium are presented.

PMID- 8550401
TI  - Disulfide cross-linked envelope proteins: the functional equivalent of
      peptidoglycan in chlamydiae?

PMID- 8550402
TI  - Construction and characterization of pyocin-colicin chimeric proteins.
AB  - Chimeric proteins were constructed from pyocin S1 or S2 and colicin E3 or E2, and
      their characteristics were investigated with special reference to the domain
      structure. The nuclease domains were interchangeable between two bacteriocins so
      that a new kind of pyocin, with RNase activity, was created. A bacteriocin which
      can kill both Pseudomonas aeruginosa and Escherichia coli was also constructed.
      Investigations with various chimeric proteins indicate that the translocation
      domain as well as the receptor-binding domain is species specific. Inhibition of
      lipid synthesis, which is characteristic of pyocins, was also observed with
      chimeric pyocins carrying the DNase domain of colicin E2 but not with those
      carrying the RNase domain of E3. Thus, the DNase domain is responsible for the
      inhibition of lipid synthesis.

PMID- 8550403
TI  - Molecular characterization of the 4-hydroxyphenylacetate catabolic pathway of
      Escherichia coli W: engineering a mobile aromatic degradative cluster.
AB  - We have determined and analyzed the nucleic acid sequence of a 14,855-bp region
      that contains the complete gene cluster encoding the 4-hydroxyphenylacetic acid
      (4-HPA) degradative pathway of Escherichia coli W (ATCC 11105). This catabolic
      pathway is composed by 11 genes, i.e., 8 enzyme-encoding genes distributed in two
      putative operons, hpaBC (4-HPA hydroxylase operon) and hpaGEDFHI (meta-cleavage
      operon); 2 regulatory genes, hpaR and hpaA; and the gene, hpaX, that encodes a
      protein related to the superfamily of transmembrane facilitators and appears to
      be cotranscribed with hpaA. Although comparisons with other aromatic catabolic
      pathways revealed interesting similarities, some of the genes did not present any
      similarity to their corresponding counterparts in other pathways, suggesting
      different evolutionary origins. The cluster is flanked by two genes homologous to
      the estA (carbon starvation protein) and tsr (serine chemoreceptor) genes of E.
      coli K-12. A detailed genetic analysis of this region has provided a singular
      example of how E. coli becomes adapted to novel nutritional sources by the
      recruitment of a catabolic cassette. Furthermore, the presence of the pac gene in
      the proximity of the 4-HPA cluster suggests that the penicillin G acylase was a
      recent acquisition to improve the ability of E. coli W to metabolize a wider
      range of substrates, enhancing its catabolic versatility. Five repetitive
      extragenic palindromic sequences that might be involved in transcriptional
      regulation were found within the cluster. The complete 4-HPA cluster was cloned
      in plasmid and transposon cloning vectors that were used to engineer E. coli K-12
      strains able to grow on 4-HPA. We report here also the in vitro design of new
      biodegradative capabilities through the construction of a transposable cassette
      containing the wide substrate range 4-HPA hydroxylase, in order to expand the
      ortho-cleavage pathway of Pseudomonas putida KT2442 and allow the new recombinant
      strain to use phenol as the only carbon source.

PMID- 8550404
TI  - A global signal transduction system regulates aerobic and anaerobic CO2 fixation
      in Rhodobacter sphaeroides.
AB  - Complementation of a mutant of Rhodobacter sphaeroides defective in
      photosynthetic CO2 reduction led to the identification of a gene which encodes a
      protein that is related to a class of sensor kinases involved in bacterial signal
      transduction. The nucleotide sequence and deduced amino acid sequence led to the
      finding that the gene which complemented the mutant is the regB (prrB) gene,
      previously isolated from both R. sphaeroides and Rhodobacter capsulatus and shown
      to regulate the anaerobic expression of structural genes required for the
      synthesis of the reaction center and light-harvesting systems of these organisms.
      The current investigation indicates that in addition to its role in the
      regulation of photosystem biosynthesis, regB (prrB) of R. sphaeroides is
      intimately involved in the positive regulation of the cbbI and cbbII Calvin cycle
      CO2 fixation operons. In addition to regulating the expression of structural
      genes encoding enzymes of the primary pathway for CO2 fixation in R. sphaeroides,
      regB was also found to be required for the expression of a gene(s) important for
      the putative alternative CO2 fixation pathway(s) of this organism. A mutation in
      regB also blocked expression of structural genes of the cbb regulon in a strain
      of R. sphaeroides capable of aerobic CO2-dependent growth in the dark. It is thus
      apparent that regB is part of a two-component system and encodes a sensor kinase
      involved in the global regulation of both anoxygenic light-dependent- and
      oxygenic light-independent CO2 fixation as well as anoxygenic photosystem
      biosynthesis.

PMID- 8550406
TI  - Expression of recA in Deinococcus radiodurans.
AB  - Deinococcus (formerly Micrococcus) radiodurans is remarkable for its
      extraordinary resistance to ionizing and UV irradiation and many other agents
      that damage DNA. This organism can repair > 100 double-strand breaks per
      chromosome induced by ionizing radiation without lethality or mutagenesis. We
      have previously observed that expression of D. radiodurans recA in Escherichia
      coli appears lethal. We now find that the RecA protein of D. radiodurans is ot
      detectable in D. radiodurans except in the setting of DNA damage and that
      termination of its synthesis is associated with the onset of deinococcal growth.
      The synthesis of Shigella flexneri RecA (protein sequence identical to that of E.
      coli RecA) in recA-defective D. radiodurans is described. Despite a large
      accumulation of the S. flexneri RecA in D. radiodurans, there is no
      complementation of any D. radiodurans recA phenotype, including DNA damage
      sensitivity, inhibition of natural transformation, or inability to support a
      plasmid that requires RecA for replication. To ensure that the cloned S. flexneri
      recA gene was not inactivated, it was rescued from D. radiodurans and was shown
      to function normally in E. coli. We conclude that neither D. radiodurans nor S.
      flexneri RecA is functional in the other species, nor are the kinetics of
      induction and suppression similar to each other, indicating a difference between
      these two proteins in their modes of action.

PMID- 8550405
TI  - The sea pansy Renilla reniformis luciferase serves as a sensitive bioluminescent
      reporter for differential gene expression in Candida albicans.
AB  - The infectious yeast Candida albicans progresses through two developmental
      programs which involve differential gene expression, the bud-hypha transition and
      high-frequency phenotypic switching. To understand how differentially expressed
      genes are regulated in this organism, the promoters of phase-specific genes must
      be functionally characterized, and a bioluminescent reporter system would
      facilitate such characterization. However, C. albicans has adopted a
      nontraditional codon strategy that involves a tRNA with a CAG anticodon to decode
      the codon CUG as serine rather than leucine. Since the luciferase gene of the sea
      pansy Renilla reinformis contains no CUGs, we have used it to develop a highly
      sensitive bioluminescent reporter system for C. albicans. When fused to the
      galactose-inducible promoter of GAL1, luciferase activity is inducible; when
      fused to the constitutive EF1 alpha 2 promoter, luciferase activity is
      constitutive; and when fused to the promoter of the white-phase-specific gene
      WH11 or the opaque-phase-specific gene OP4, luciferase activity is phase
      specific. The Renilla luciferase system can, therefore, be used as a
      bioluminescent reporter to analyze the strength and developmental regulation of
      C. albicans promoters.

PMID- 8550407
TI  - Cloning, purification, and properties of a phosphotyrosine protein phosphatase
      from Streptomyces coelicolor A3(2).
AB  - We describe the isolation and characterization of a gene (ptpA) from Streptomyces
      coelicolor A3(2) that codes for a protein with a deduced M(r) of 17,690
      containing significant amino acid sequence identity with mammalian and
      prokaryotic small, acidic phosphotyrosine protein phosphatases (PTPases). After
      expression of S. coelicolor ptpA in Escherichia coli with a pT7-7-based vector
      system, PtpA was purified to homogeneity as a fusion protein containing five
      extra amino acids. The purified fusion enzyme catalyzed the removal of phosphate
      from p-nitrophenylphosphate (PNPP), phosphotyrosine (PY), and a commercial
      phosphopeptide containing a single phosphotyrosine residue but did not cleave
      phosphoserine or phosphothreonine. The pH optima for PNPP and PY hydrolysis by
      PtpA were 6.0 and 6.5, respectively. The Km values for hydrolysis of PNPP and PY
      by PtpA were 0.75 mM (pH 6.0, 37 degrees C) and 2.7 mM (pH 6.5, 37 degrees C),
      respectively. Hydrolysis of PNPP by S. coelicolor PtpA were 0.75 mM (pH 6.0, 37
      degrees C) and 2.7 mM (pH 6.5, 37 degrees C), respectively. Hydrolysis of PNPP by
      S. coelicolor PtpA was competitively inhibited by dephostatin with a Ki of 1.64
      microM; the known PTPase inhibitors phenylarsine oxide, sodium vanadate, and
      iodoacetate also inhibited enzyme activity. Apparent homologs of ptpA were
      detected in other streptomycetes by Southern hybridization; the biological
      functions of PtpA and its putative homologs in streptomycetes are not yet known.

PMID- 8550408
TI  - Cloning, functional organization, transcript studies, and phylogenetic analysis
      of the complete nitrogenase structural genes (nifHDK2) and associated genes in
      the archaeon Methanosarcina barkeri 227.
AB  - Determination of the nucleotide sequence of the nitrogenase structural genes
      (nifHDK2) from Methanosarcina barkeri 227 was completed in this study by cloning
      and sequencing a 2.7-kb BamHI fragment containing the 3' end of nifK2 and 1,390
      bp of the nifE2-homologous genes. Open reading frame nifK2 is 1,371 bp long
      including the stop codon TAA and encodes a polypeptide of 456 amino acids.
      Phylogenetic analysis of the deduced amino acid sequences of the nifK2 and nifE2
      gene products from M. barkeri showed that both genes cluster most closely with
      the corresponding nif-1 gene products from Clostridium pasteurianum, consistent
      with our previous analyses of nifH2 and nifD2. The nifE gene product is known to
      be homologous to that of nifD, and our analysis shows that the branching pattern
      for the nifE proteins resembles that for the nifD product (with the exception of
      vnfE from Azotobacter vinelandii), suggesting that a gene duplication occurred
      before the divergence of nitrogenases. Primer extension showed that nifH2 had a
      single transcription start site located 34 nucleotides upstream of the ATG
      translation start site for nifH2, and a sequence resembling the archaeal
      consensus promoter sequence [TTTA(A/T)ATA] was found 32 nucleotides upstream from
      that transcription start site. A tract of four T's, previously identified as a
      transcription termination site in archaea, was found immediately downstream of
      the nifK2 gene, and a potential promoter was located upstream of the nifE2 gene.
      Hybridization with nifH2 and nifDK2 probes with M. barkeri RNA revealed a 4.6-kb
      transcript from N2-grown cells, large enough to harbor nifHDK genes and their
      internal open reading frames, while no transcript was detected from NH4(+)-grown
      cells. These results support a model in which the nitrogenase structural genes in
      M. barkeri are cotranscribed in a single NH4(+)-repressed operon.

PMID- 8550409
TI  - Characterization and phylogeny of the pfp gene of Amycolatopsis methanolica
      encoding PPi-dependent phosphofructokinase.
AB  - The actinomycete Amycolatopsis methanolica employs a PPi-dependent
      phosphofructokinase (PPi-PFK) (EC 2.7.1.90) with biochemical characteristics
      similar to those of both ATP- and PPi-dependent enzymes during growth on glucose.
      A 2.3-kb PvuII fragment hybridizing to two oligonucleotides based on the amino
      terminal amino acid sequence of PPi-PFK was isolated from a genomic library of A.
      methanolica. Nucleotide sequence analysis of this fragment revealed the presence
      of an open reading frame encoding a protein of 340 amino acids with a high degree
      of similarity to PFK proteins. Heterologous expression of this open reading frame
      in Escherichia coli gave rise to a unique 45-kDa protein displaying a high level
      of PPi-PFK activity. The open reading frame was therefore designated pfp,
      encoding the PPi-PFK of A. methanolica. Upstream and transcribed divergently from
      pfp, a partial open reading frame (aroA) similar to 3-deoxy-D-arabino
      heptulosonate-7-phosphate synthase-encoding genes was identified. The partial
      open reading frame (chiA) downstream from pfp was similar to chitinase genes from
      Streptomyces species. A phylogenetic analysis of the ATP- and PPi-dependent
      proteins showed that PPi-PFK enzymes are monophyletic, suggesting that the two
      types of PFK evolved from a common ancestor.

PMID- 8550410
TI  - The ToxR protein of Vibrio cholerae forms homodimers and heterodimers.
AB  - The ToxR protein of Vibrio cholerae regulates the expression of several virulence
      factors that play important roles in the pathogenesis of cholera. Previous
      experiments with ToxR-alkaline phosphatase (ToxR-PhoA) fusion proteins suggested
      a model for gene regulation in which the inactive form of ToxR was a monomer and
      the active form of ToxR was a dimer (V. L. Miller, R. K. Taylor, and J. J.
      Mekalanos, Cell 48:271-279, 1987). In order to examine whether ToxR exists in a
      dimeric form in vivo, biochemical cross-linking analyses were carried out.
      Different dimeric cross-linked species were detected depending on the expression
      level of ToxR: when overexpressed, ToxR+ToxR homodimers and ToxR+ToxS
      heterodimers were detected, and when ToxR was expressed at normal levels,
      exclusively ToxR+ToxS heterodimers were detected. The amount of overexpression
      was quantitated by using ToxR-PhoA fusion proteins and was found to correspond to
      2.7-fold the normal level of ToxR. The formation of both homodimeric ToxR species
      and heterodimeric ToxR+ToxS species is consistent with previously reported
      genetic data that suggested that both types of ToxR oligomeric interactions
      occur. However, variation in the amount of either the homodimeric or
      heterodimeric form detectable by this cross-linking analysis was not observed to
      correlate with laboratory culture conditions known to modulate ToxR activity.
      Thus, genetic and biochemical data indicate that ToxR is able to interact with
      both itself and ToxS but that these interactions may not explain mechanistically
      the observed changes in ToxR activity that occur in response to environmental
      conditions.

PMID- 8550411
TI  - Molybdenum and vanadium do not replace tungsten in the catalytically active forms
      of the three tungstoenzymes in the hyperthermophilic archaeon Pyrococcus
      furiosus.
AB  - Three different types of tungsten-containing enzyme have been previously purified
      from Pyrococcus furiosus (optimum growth temperature, 100 degrees C): aldehyde
      ferredoxin oxidoreductase (AOR), formaldehyde ferredoxin oxidoreductase (FOR),
      and glyceraldehyde-3-phosphate oxidoreductase (GAPOR). In this study, the
      organism was grown in media containing added molybdenum (but not tungsten or
      vanadium) or added vanadium (but not molybdenum or tungsten). In both cell types,
      there were no dramatic changes compared with cells grown with tungsten, in the
      specific activities of hydrogenase, ferredoxin:NADP oxidoreductase, or the 2-keto
      acid ferredoxin oxidoreductases specific for pyruvate, indolepyruvate, 2
      ketoglutarate, and 2-ketoisovalerate. Compared with tungsten-grown cells, the
      specific activities of AOR, FOR, and GAPOR were 40, 74, and 1%, respectively, in
      molybdenum-grown cells, and 7, 0, and 0%, respectively, in vanadium-grown cells.
      AOR purified from vanadium-grown cells lacked detectable vanadium, and its
      tungsten content and specific activity were both ca. 10% of the values for AOR
      purified from tungsten-grown cells. AOR and FOR purified from molybdenum-grown
      cells contained no detectable molybdenum, and their tungsten contents and
      specific activities were > 70% of the values for the enzymes purified from
      tungsten-grown cells. These results indicate that P. furiosus uses exclusively
      tungsten to synthesize the catalytically active forms of AOR, FOR, and GAPOR, and
      active molybdenum- or vanadium-containing isoenzymes are not expressed when the
      cells are grown in the presence of these other metals.

PMID- 8550412
TI  - Naturally occurring peptidoglycan variants of Streptococcus pneumoniae.
AB  - Analysis by high-performance liquid chromatography of the stem peptide
      composition of cell walls purified from a large number of pneumococcal strains
      indicates that these bacteria produce a highly conserved species-specific
      peptidoglycan independent of serotype, isolation date, and geographic origin.
      Characteristic features of this highly reproducible peptide pattern are the
      dominance of linear stem peptides with a monomeric tripeptide, a tri-tetra linear
      dimer, and two indirectly cross-linked tri-tetra dimers being the most abundant
      components. Screening of strains with the high-performance liquid chromatography
      technique has identified two naturally occurring peptidoglycan variants in which
      the species-specific stem peptide composition was replaced by two drastically
      different and distinct stem peptide patterns, each unique to the particular clone
      of pneumococci producing it. Both isolates were multidrug resistant, including
      resistance to penicillin. In one of these clones--defined by multilocus enzyme
      analysis and pulsed-field gel electrophoresis of the chromosomal DNAs--the linear
      stem peptides were replaced by branched peptides that most frequently carried an
      alanyl-alanine substituent on the epsilon amino group of the diamino acid
      residue. In the second clone, the predominant stem peptide species replacing the
      linear stem peptides carried a seryl-alanine substituent. The abnormal
      peptidoglycans may be related to the altered substrate preference of
      transpeptidases (penicillin-binding proteins) in the pneumococcal variants.

PMID- 8550413
TI  - The intercellular adhesin involved in biofilm accumulation of Staphylococcus
      epidermidis is a linear beta-1,6-linked glucosaminoglycan: purification and
      structural analysis.
AB  - The primary attachment to polymer surfaces followed by accumulation in
      multilayered cell clusters leads to biofilm production of Staphylococcus
      epidermidis, which is thought to contribute to virulence in biomaterial-related
      infections. We purified a specific polysaccharide antigen of biofilm-producing S.
      epidermidis 1457 and RP62A, which was recently shown to have a function in the
      accumulative phase of biofilm production by mediating intercellular adhesion (D.
      Mack, M. Nedelmann, A. Krokotsch, A. Schwarzkopf, J. Heesemann, and R. Laufs,
      Infect. Immun. 62:3244-3253, 1994). Following Sephadex G-200 gel filtration, this
      antigen was separated by Q-Sepharose chromatography into a major polysaccharide,
      polysaccharide I (> 80%), which did not bind to Q-Sepharose, and a minor
      polysaccharide, polysaccharide II (< 20%), which was moderately anionic. As shown
      by chemical analyses and nuclear magnetic resonance spectroscopy, polysaccharide
      I is a linear homoglycan of at least 130 beta-1,6-linked 2-deoxy-2-amino-D
      glucopyranosyl residues. On average, 80 to 85% of them are N acetylated; the rest
      are non-N-acetylating and positively charged. Chain cleavage by deamination with
      HNO2 revealed a more or less random distribution of the non-N-acetylated
      glucosaminyl residues, with some prevalence of glucosaminyl-rich sequences.
      Cation-exchange chromatography separated molecular species whose content of non-N
      acetylated glucosaminyl residues varied between 2 and 26%. Polysaccharide II is
      structurally related to polysaccharide I but has a lower content of non-N
      acetylated D-glucosaminyl residues and contains phosphate and ester-linked
      succinate, rendering it anionic. Enzyme-linked immunosorbent assay inhibition
      with various monosaccharides revealed the beta-anomeric form and the acetylated
      amino group of the D-glucosaminyl residues as important for reactivity with the
      specific antiserum. The unbranched polysaccharide structure favors long-range
      contacts and interactions between polysaccharide strands and the cell wall and/or
      lectin-like proteins, leading to intercellular adhesion and biofilm accumulation.
      The structure of the polysaccharide is, so far, considered to be unique and,
      according to its function, is referred to as S. epidermidis polysaccharide
      intercellular adhesin (PIA).

PMID- 8550414
TI  - Preferential binding of Escherichia coli RecF protein to gapped DNA in the
      presence of adenosine (gamma-thio) triphosphate.
AB  - Escherichia coli RecF protein binds, but does not hydrolyze, ATP. To determine
      the role that ATP binding to RecF plays in RecF protein-mediated DNA binding, we
      have determined the interaction between RecF protein and single-stranded (ss)DNA,
      double-stranded (ds)DNA, and dsDNA containing ssDNA regions (gapped [g]DNA)
      either alone or in various combinations both in the presence and in the absence
      of adenosine (gamma-thio) triphosphate, gamma-S-ATP, a nonhydrolyzable ATP
      analog. Protein-DNA complexes were analyzed by electrophoresis on agarose gels
      and visualized by autoradiography. The type of protein-DNA complexes formed in
      the presence of gamma-S-ATP was different with each of the DNA substrates and
      from those formed in the absence of gamma-S-ATP. Competition experiments with
      various combinations of DNA substrates indicated that RecF protein preferentially
      bound gDNA in the presence of gamma-S-ATP, and the order of preference of binding
      was gDNA > dsDNA > ssDNA. Since gDNA has both ds- and ssDNA components, we
      suggest that the role for ATP in RecF protein-DNA interactions in vivo is to
      confer specificity of binding to dsDNA-ssDNA junctions, which is necessary for
      catalyzing DNA repair and recombination.

PMID- 8550415
TI  - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase from Haloferax volcanii:
      purification, characterization, and expression in Escherichia coli.
AB  - Prior work from this laboratory characterized eukaryotic (hamster) and
      eubacterial (Pseudomonas mevalonii) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductases. We report here the characterization of an HMG-CoA reductase from
      the third domain, the archaea. HMG-CoA reductase of the halobacterium Haloferax
      volcanii was initially partially purified from extracts of H. volcanii.
      Subsequently, a portion of the H. volcanii lovastatin (formerly called mevinolin)
      resistance marker mev was subcloned into the Escherichia coli expression vector
      pT7-7. While no HMG-CoA reductase activity was detectable following expression in
      E. coli, activity could be recovered after extracts were exposed to 3 M KCl.
      Following purification to electrophoretic homogeneity, the specific activity of
      the expressed enzyme, 24 microU/mg, equaled that of homogeneous hamster or P.
      mevalonii HMG-CoA reductase. Activity was optimal at pH 7.3. Kms were 66 microM
      (NADPH) and 60 microM [(S)-HMG-CoA]. (R)-HMG-CoA and lovastatin inhibited
      competitively with (S)-HMG-CoA. H. volcanii HMG-CoA reductase also catalyzed the
      reduction of mevaldehyde [optimal activity at pH 6.0; Vmax 11 microU/mg; Kms 32
      microM (NADPH), 550 microM [(R,S)-mevaldehyde]] and the oxidative acylation of
      mevaldehyde [optimal activity at pH 8.0; Vmax 2.1 microU/mg; Kms 350 microM
      (NADP+), 300 microM (CoA), 470 microM [(R,S)-mevaldehyde]]. These properties are
      comparable to those of hamster and P. mevalonii HMG-CoA reductases, suggesting a
      similar catalytic mechanism.

PMID- 8550416
TI  - Homology among nearly all plasmids infecting three Bacillus species.
AB  - We have surveyed naturally occurring plasmids in strains of Bacillus subtilis and
      the closely related species B. mojavensis and B. licheniformis. Previous studies
      have failed to find host-benefitting functions for plasmids of these species,
      suggesting that these plasmids are nonmutualistic. Only one type of plasmid was
      found in each plasmid-bearing strain, suggesting that most of the plasmids
      infecting these Bacillus species are in the same incompatibility group. A sample
      of 18 plasmids from these species ranged in size from 6.9 to 16 kb, with all but
      6 plasmids falling into three size groups. These groups differed in the sizes of
      their host ranges and geographical ranges. All but 1 of the 18 plasmids from
      these three host species are homologous with one another. The cryptic plasmids
      from these three species are far less diverse than are plasmids (from other
      species) that are known to benefit their bacterial hosts. The low-level diversity
      among these cryptic plasmids is consistent with the hypothesis that host
      benefitting adaptations play an important role in fostering the coexistence of
      plasmid populations, but other explanations for the low-level plasmid diversity
      are possible. Comparison of the phylogenies of the plasmids with those of their
      hosts suggests that Bacillus plasmids are horizontally transferred in nature at a
      low rate similar to that found for the colicin plasmids of Escherichia coli.

PMID- 8550417
TI  - The nucleotide concentration determines the specificity of in vitro transcription
      activation by the sigma 54-dependent activator FhlA.
AB  - An in vitro transcription system has been set up for formate- and FhlA-dependent
      transcription activation at the -12/-24 promoter of the fdhF gene from
      Escherichia coli by sigma 54-RNA polymerase. It requires the presence of the
      upstream activation sequence on supercoiled DNA. Transcription is independent
      from the effector formate at nucleoside triphosphate concentrations of 400 microM
      and above and completely dependent on the presence of the effector when the
      concentration is lowered to 300 microM. Inclusion of nucleoside diphosphates in
      the system raises the nucleoside triphosphate level at which specific induction
      by formate can take place. The threshold level of FhlA relative to that of
      template DNA required for transcription activation in the absence of formate was
      lowered at a high nucleoside triphosphate concentration. On the other hand,
      transcription activation at the fdhF promoter lacking the upstream activation
      sequence requires an increased ratio of FhlA to promoter plus the presence of
      formate; high ATP concentrations cannot bypass the effect of formate. These
      results are interpreted in terms of a model which implies that FhlA must undergo
      a change in its oligomeric state for transcription activation and that this
      oligomerization is favored by high nucleoside triphosphate concentrations, by the
      effector formate, and by the target DNA. In the absence of the target DNA, FhlA
      can line up at unspecific DNA and activate transcription; in this case, however,
      presence of formate and a higher FhlA concentration are required to stabilize and
      increase the amount of active oligomer.

PMID- 8550418
TI  - Characteristics of orf1 and orf2 in the anfHDGK genomic region encoding
      nitrogenase 3 of Azotobacter vinelandii.
AB  - In Azotobacter vinelandii, the anfHDGK operon encodes the subunits for the third
      nitrogenase complex. Two open reading frames (orf1 and orf2) located immediately
      downstream of anfK were shown to be required for diazotrophic growth under Mo-
      and V-deficient conditions. We have designated orf1 and orf2 anfO and anfR,
      respectively. Strains (CA115 and CA116) carrying in-frame deletions in anfO and
      anfR accumulate the subunits for nitrogenase 3 under Mo-deficient diazotrophic
      conditions. AnfO and AnfR are required for nitrogenase 3-dependent diazotrophic
      growth and 15N2 incorporation but not for acetylene reduction. AnfO contains a
      putative heme-binding domain that exhibits similarity to presumed heme-binding
      domains of P-450 cytochromes. Amino acid substitutions of Cys-158 show that this
      residue is required for fully functional AnfO as measured by diazotrophic growth
      under Mo- and V-deficient conditions. The nucleotide sequence of the region
      located immediately downstream of anfR has been determined. A putative rho
      independent transcription termination site has been identified 250 bp from the 3'
      end of anfR. A third open reading frame (orf3), located downstream of anfR, does
      not appear to be required for diazotrophic growth under Mo- and V-deficient
      conditions.

PMID- 8550419
TI  - Halovibrin, secreted from the light organ symbiont Vibrio fischeri, is a member
      of a new class of ADP-ribosyltransferases.
AB  - The purification, cloning, and deduced amino acid sequence of an ADP
      ribosyltransferase secreted from the marine bacterium Vibrio fischeri (V.
      fischeri ADP-r) is described. This enzyme was purified from culture supernatant,
      and partial amino acid sequence obtained from the purified protein was used to
      design a degenerate oligonucleotide probe that was used to clone a cross
      hybridizing DNA fragment from V. fischeri genomic DNA. Recombinant Escherichia
      coli clones harboring this fragment possessed ADP-ribosyltransferase activity.
      The DNA fragment was sequenced, and deletion analysis localized the ADP
      ribosyltransferase activity to one of the three possible open reading frames in
      the fragment; the deduced amino acid sequence from this open reading frame
      matched the amino acid sequence obtained from the purified protein. V. fischeri
      ADP-r has no significant homology (DNA or amino acid) with other known ADP
      ribosyltransferases. This enzyme appears to require neither proteolytic cleavage
      nor a reducing agent for enzymatic activity. The cloned gene is expressed but not
      secreted in E. coli; however, it is secreted from a heterologous marine Vibrio
      species. We have named this enzyme halovibrin.

PMID- 8550420
TI  - Transcription of Bacillus subtilis degR is sigma D dependent and suppressed by
      multicopy proB through sigma D.
AB  - Production of Bacillus subtilis exoproteases is positively regulated by the DegS
      DegU two-component regulatory system and other regulatory factors including DegR
      and ProB. It was shown that the expression of degR was virtually abolished in a
      sigD mutant and that the transcriptional initiation site in vivo is preceded by a
      sequence very similar to the consensus sequence of sigma D-recognized promoters.
      Alteration of the -10 sequence of the putative promoter greatly reduced the
      expression of degR. These results show that degR expression is driven by the
      alternative sigma factor, sigma D. It was found that degR expression was
      suppressed by multiple copies of proB on plasmid pLC1 and that this suppression
      was exerted at the transcriptional level through a target in the vicinity of the
      degR promoter. Furthermore, it was shown that the expression of another sigma D
      directed gene, hag, was suppressed by pLC1. Suppression by pLC1 diminished when
      the sequence of the -10 element of the degR promoter was changed to a sigma A
      like promoter sequence. pLC1, however, did not suppress sigD expression. On the
      basis of these results, we conclude that multicopy proB on pLC1 inhibits
      transcription from sigma D-driven promoters by affecting some posttranscriptional
      process of sigma D.

PMID- 8550421
TI  - Torque generation in the flagellar motor of Escherichia coli: evidence of a
      direct role for FliG but not for FliM or FliN.
AB  - Among the many proteins needed for assembly and function of bacterial flagella,
      FliG, FliM, and FliN have attracted special attention because mutant phenotypes
      suggest that they are needed not only for flagellar assembly but also for torque
      generation and for controlling the direction of motor rotation. A role for these
      proteins in torque generation is suggested by the existence of mutations in each
      of them that produce the Mot- (or paralyzed) phenotype, in which flagella are
      assembled and appear normal but do not rotate. The presumption is that Mot-
      defects cause paralysis by specifically disrupting functions essential for torque
      generation, while preserving the features of a protein needed for flagellar
      assembly. Here, we present evidence that the reported mot mutations in fliM and
      fliN do not disrupt torque-generating functions specifically but, instead, affect
      the incorporation of proteins into the flagellum. The fliM and fliN mutants are
      immotile at normal expression levels but become motile when the mutant proteins
      and/or other, evidently interacting flagellar proteins are overexpressed. In
      contrast, many of the reported fliG mot mutations abolish motility at all
      expression levels, while permitting flagellar assembly, and thus appear to
      disrupt torque generation specifically. These mutations are clustered in a
      segment of about 100 residues at the carboxyl terminus of FliG. A slightly larger
      carboxyl-terminal segment of 126 residues accumulates in the cells when expressed
      alone and thus probably constitutes a stable, independently folded domain. We
      suggest that the carboxyl-terminal domain of FliG functions specifically in
      torque generation, forming the rotor portion of the site of energy transduction
      in the flagellar motor.

PMID- 8550423
TI  - Escherichia coli fliAZY operon.
AB  - We have cloned the Escherichia coli fliAZY operon, which contains the fliA gene
      (the alternative sigma factor sigma F) and two novel genes, fliZ and fliY.
      Transcriptional mapping of this operon shows two start sites, one of which is
      preceded by a canonical E sigma F-dependent consensus and is dependent on sigma F
      for expression in vivo and in vitro. We have overexpressed and purified sigma F
      and demonstrated that it can direct core polymerase to E sigma F-dependent
      promoters. FliZ and FliY are not required for motility but may regulate sigma F
      activity, perhaps in response to a putative cell density signal that may be
      detected by FliY, a member of the bacterial extracellular solute-binding protein
      family 3.

PMID- 8550422
TI  - A novel alpha-ketoglutarate reductase activity of the serA-encoded 3
      phosphoglycerate dehydrogenase of Escherichia coli K-12 and its possible
      implications for human 2-hydroxyglutaric aciduria.
AB  - Escherichia coli serA-encoded 3-phosphoglycerate (3PG) dehydrogenase catalyzes
      the first step of the major phosphorylated pathway of L-serine (Ser)
      biosynthesis. The SerA enzyme is evolutionarily related to the pdxB gene product,
      4-phosphoerythronate dehydrogenase, which catalyzes the second step in one branch
      of pyridoxal 5'-phosphate coenzyme biosynthesis. Both the Ser and pyridoxal 5'
      phosphate biosynthetic pathways use the serC(pdxF)-encoded transaminase in their
      next steps. In an analysis of these parallel pathways, we attempted to couple the
      transaminase and dehydrogenase reactions in the reverse direction. Unexpectedly,
      we found that the SerA enzyme catalyzes a previously undetected reduction of
      alpha-ketoglutarate (alpha KG) to 2-hydroxyglutaric acid (HGA). Numerous criteria
      ruled out the possibility that this SerA alpha KG reductase activity was caused
      by contamination in the substrate or purified enzyme preparations. HGA was
      confirmed as the product of the SerA alpha KG reductase reaction by thin-layer
      chromatography and by enzyme assays showing that both the D- and L-isomers of HGA
      were substrates for the reverse (dehydrogenase) reaction. Detailed steady-state
      kinetic analyses showed that alpha KG reduction (apparent Michaelis-Menten
      constant [Km(app)] = 88 microM; apparent catalytic constant [kcat(app)] = 33.3 s
      1) and 3-phosphohydroxypyruvate reduction (Km(app) = 3.2 microM; kcatapp = 27.8 s
      1), which is the reverse reaction of 3PG oxidation, were the major in vitro
      activities of the SerA enzyme. The SerA alpha KG reductase was inhibited by Ser,
      D-HGA, 3PG, and glycine (Gly), whereas the D-HGA dehydrogenase was inhibited by
      Ser, alpha KG, 3-phosphohydroxypyruvate, and Gly. The implications of these
      findings for the regulation of Ser biosynthesis, the recycling of NADH, and the
      enzymology of 2-hydroxyacid dehydrogenases are discussed. Since the same pathway
      of Ser biosynthesis seems to be present in all organisms, these results suggest
      that a mutation in the human SerA homolog may contribute to the neurometabolic
      diseases D- and L-2-hydroxyglutaric aciduria, which lead to the accumulation of D
      HGA and L-HGA, respectively.

PMID- 8550424
TI  - Identification of the O antigen polymerase (rfc) gene in Escherichia coli O4 by
      insertional mutagenesis using a nonpolar chloramphenicol resistance cassette.
AB  - Computer analysis of the O4 polysaccharide gene cluster of Escherichia coli
      revealed the presence of two open reading frames (ORFs) encoding strongly
      hydrophobic polypeptides. O antigen polymerase, which is encoded by the rfc gene,
      is a potential membrane protein and therefore should be hydrophobic. To identify
      the rfc gene, these two ORFs were subjected to insertional mutagenesis. A
      chloramphenicol resistance cassette was designed which, when properly inserted,
      does not cause a polar effect in downstream genes. Each of two ORFs, cloned into
      a plasmid vector, was inactivated with this cassette. Two types of mutants
      bearing chromosomal insertions of the cassettes in each ORF were constructed by
      homologous recombination. These mutants were characterized by PCR, Southern
      blotting, and transverse-alternating-field electrophoresis. Only one class of
      mutants exhibited the expected O polymerase-deficient phenotype; they produced O4
      specific, semirough lipopolysaccharide. Therefore, this ORF was identified as the
      rfc gene. The chromosomal rfc mutation was complemented in trans by the rfc gene
      expressed from a plasmid vector.

PMID- 8550425
TI  - Molecular and phylogenetic characterization of pyruvate and 2-ketoisovalerate
      ferredoxin oxidoreductases from Pyrococcus furiosus and pyruvate ferredoxin
      oxidoreductase from Thermotoga maritima.
AB  - Previous studies have shown that the hyperthermophilic archaeon Pyrococcus
      furiosus contains four distinct cytoplasmic 2-ketoacid oxidoreductases (ORs)
      which differ in their substrate specificities, while the hyperthermophilic
      bacterium Thermotoga maritima contains only one, pyruvate ferredoxin
      oxidoreductase (POR). These enzymes catalyze the synthesis of the acyl (or aryl)
      coenzyme A derivative in a thiamine PPi-dependent oxidative decarboxylation
      reaction with reduction of ferredoxin. We report here on the molecular analysis
      of the POR (por) and 2-ketoisovalerate ferredoxin oxidoreductase (vor) genes from
      P. furiosus and of the POR gene from T. maritima, all of which comprise four
      different subunits. The operon organization for P. furiosus POR and VOR was porG
      vorDAB-porDAB, wherein the gamma subunit is shared by the two enzymes. The operon
      organization for T. maritima POR was porGDAB. The three enzymes were 46 to 53%
      identical at the amino acid level. Their delta subunits each contained two
      ferredoxin-type [4Fe-4S] cluster binding motifs (CXXCXXCXXXCP), while their beta
      subunits each contained four conserved cysteines in addition to a thiamine PPi
      binding domain. Amino-terminal sequence comparisons show that POR, VOR,
      indolepyruvate OR, and 2-ketoglutarate OR of P. furiosus all belong to a
      phylogenetically homologous OR family. Moreover, the single-subunit pyruvate ORs
      from mesophilic and moderately thermophilic bacteria and from an amitochondriate
      eucaryote each contain four domains which are phylogenetically homologous to the
      four subunits of the hyperthermophilic ORs (27% sequence identity). Three of
      these subunits are also homologous to the dimeric POR from a mesophilic archaeon,
      Halobacterium halobium (21% identity). A model is proposed to account for the
      observed phenotypes based on genomic rearrangements of four ancestral OR
      subunits.

PMID- 8550426
TI  - FliG and FliM distribution in the Salmonella typhimurium cell and flagellar basal
      bodies.
AB  - Salmonella typhimurium FliG and FliM are two of three proteins known to be
      necessary for flagellar morphogenesis as well as energization and switching of
      flagellar rotation. We have determined FliG and FliM levels in cellular fractions
      and in extended flagellar basal bodies, using antibodies raised against the
      purified proteins. Both proteins were found predominantly in the detergent
      solubilized particulate fraction containing flagellar structures. Basal flagellar
      fragments could be separated from partially constructed basal bodies by gel
      filtration chromatography. FliG and FliM were present in an approximately
      equimolar ration in all gel-filtered fractions. FliG and FliM copy numbers,
      estimated relative to that of the hook protein from the early fractions
      containing long, basal, flagellar fragments, were (means +/- standard errors) 41
      +/- 10 and 37 +/- 13 per flagellum, respectively. Extended structures were
      present in the earliest identifiable basal bodies. Immunoelectron microscopy and
      immunoblot gel analysis suggested that the FliG and, to a less certain degree,
      the FliM contents of these structures were the same as those for the complete
      basal bodies. These facts are consistent with the postulate that FliG and FliM
      affect flagellar morphogenesis as part of the extended basal structure, formation
      of which is necessary for assembly of more-distal components of the flagellum.
      The determined stoichiometries will provide important constraints to modelling
      energization and switching of flagellar rotation.

PMID- 8550427
TI  - Characterization of PcaQ, a LysR-type transcriptional activator required for
      catabolism of phenolic compounds, from Agrobacterium tumefaciens.
AB  - Previous work demonstrated that catabolism of the phenolic compounds p
      hydroxybenzoate and protocatechuate via the beta-ketoadipate pathway in
      Agrobacterium tumefaciens is mediated by a regulatory gene, pcaQ, that acts in
      trans to elicit expression of many of the enzymes encoded by the pca genes. There
      was evidence that five pca structural genes are organized in a polycistronic
      operon transcribed in the order pcaDCHGB. The pcaQ gene is upstream of this
      operon. The activator encoded by pcaQ was novel in having the metabolite beta
      carboxy-cis,cis-muconate as a coinducer. This communication reports the
      nucleotide sequence of pcaQ and identifies its deduced polypeptide product as a
      member of the LysR family of regulatory molecules. PcaQ has a calculated
      molecular weight of 33,546, which is consistent with the size of LysR relatives.
      Like many other LysR members, PcaQ serves as an activator at the level of
      transcription, it has a conserved amino-terminal domain, and its gene is
      transcribed divergently from the operon that it regulates and is subject to
      negative autoregulation. Studies of coinducer specificity identified an unstable
      pathway metabolite, gamma-carboxymuconolactone, as a second coinducer. Analysis
      of expression from a pcaD::lacZ promoter probe plasmid revealed that PcaQ and the
      coinducer exert their effect on a 133-nucleotide region upstream of pcaD. The
      nucleotide sequence of this region in a mutant strain constitutive for enzymes
      encoded by the pcaDCHGB operon identified nucleotides likely to be involved in
      the pcaDCHGB promoter and substantiated the inclusion of five pca structural
      genes in the operon.

PMID- 8550429
TI  - Frur mediates catabolite activation of pyruvate kinase (pykF) gene expression in
      Escherichia coli.
AB  - Expression of a pykF-lacZ fusion was studied as a function of the carbon source
      in wild-type strains and strains lacking or overproducing the FruR protein of
      Escherichia coli. FruR controls the response to the carbon source by repressing
      pykF expression more strongly under gluconeogenic than under glycolytic
      conditions, a phenomenon we term catabolite activation.

PMID- 8550428
TI  - Allelic exchange in Mycobacterium tuberculosis with long linear recombination
      substrates.
AB  - Genetic studies of Mycobacterium tuberculosis have been greatly hampered by the
      inability to introduce specific chromosomal mutations. Whereas the ability to
      perform allelic exchanges has provided a useful method of gene disruption in
      other organisms, in the clinically important species of mycobacteria, such as M.
      tuberculosis and Mycobacterium bovis, similar approaches have thus far been
      unsuccessful. In this communication, we report the development of a shuttle
      mutagenesis strategy that involves the use of long linear recombination
      substrates to reproducibly obtain recombinants by allelic exchange in M.
      tuberculosis. Long linear recombination substrates, approximately 40 to 50 kb in
      length, were generated by constructing libraries in the excisable cosmid vector
      pYUB328. The cosmid vector could be readily excised from the recombinant cosmids
      by digestion with PacI, a restriction endonuclease for which there exist few, if
      any, sites in mycobacterial genomes. A cosmid containing the mycobacterial leuD
      gene was isolated, and a selectable marker conferring resistance to kanamycin was
      inserted into the leuD gene in the recombinant cosmid by interplasmid
      recombination in Escherichia coli. A long linear recombination substrate
      containing the insertionally mutated leuD gene was generated by PacI digestion.
      Electroporation of this recombination substrate containing the insertionally
      mutated leuD allele resulted in the generation of leucine auxotrophic mutants by
      homologous recombination in 6% of the kanamycin-resistant transformants for both
      the Erdman and H37Rv strains of M. tuberculosis. The ability to perform allelic
      exchanges provides an important approach for investigating the biology of this
      pathogen as well as developing new live-cell M. tuberculosis-based vaccines.

PMID- 8550430
TI  - Serine protease EpiP from Staphylococcus epidermidis catalyzes the processing of
      the epidermin precursor peptide.
AB  - The function of serine protease EpiP in epidermin biosynthesis was investigated.
      Epidermin is synthesized as a 52-amino-acid precursor peptide, EpiA, which is
      posttranslationally modified and processed to the mature 22-amino-acid peptide
      antibiotic. epiP was expressed in Staphylococcus carnosus with xylose-regulated
      expression vector pCX15. The cleavage of the unmodified EpiA precursor peptide to
      leader peptide and proepidermin by EpiP-containing culture filtrates of S.
      carnosus (pCX15epiP) was followed by reversed-phase chromatography and subsequent
      electrospray mass spectrometry.

PMID- 8550431
TI  - Purification and in vitro phosphorylation of Myxococcus xanthus AsgA protein.
AB  - The deduced amino acid sequence of the Myxococcus xanthus AsgA protein contains
      an N-terminal domain that is homologous to the receiver of response regulators
      and a C-terminal domain that is homologous to the transmitter of histidine
      protein kinases. We overexpressed affinity-tagged AsgA in Escherichia coli,
      purified the recombinant protein, and showed that AsgA has autokinase activity in
      vitro. The results of chemical-stability assays suggest that AsgA is
      phosphorylated on a histidine and provide no evidence for transfer of the
      phosphoryl group to the conserved aspartate of the receiver domain.

PMID- 8550432
TI  - Serratia marcescens contains a heterodimeric HU protein like Escherichia coli and
      Salmonella typhimurium.
AB  - Homologs of the dimeric HU protein of Escherichia coli can be found in every
      prokaryotic organism that has been analyzed. In this work, we demonstrate that
      Serratia marcescens synthesizes two distinct HU subunits, like E. coli and
      Salmonella typhimurium, suggesting that the heterodimeric HU protein could be a
      common feature of enteric bacteria. A phylogenetic analysis of the HU-type
      proteins (HU and IHF) is presented, and a scheme for the origin of the hup genes
      and the onset of HU heterodimericity is suggested.

PMID- 8550433
TI  - Maleylacetate reductases in chloroaromatic-degrading bacteria using the modified
      ortho pathway: comparison of catalytic properties.
AB  - The maleylacetate reductases from Pseudomonas aeruginosa RHO1 and Alcaligenes
      eutrophus JMP134 were tested for activity and affinity to various maleylacetates
      as well as dechlorinating properties. The dechlorinating activity and the kcat/Km
      values revealed high-level similarity of these reductases to that of Pseudomonas
      sp. strain B13.

PMID- 8550434
TI  - Cloning and overexpression in Escherichia coli of the genes encoding NAD
      dependent alcohol dehydrogenase from two Sulfolobus species.
AB  - The gene adh encoding a NAD-dependent alcohol dehydrogenase from the novel strain
      RC3 of Sulfolobus sp. was cloned and sequenced. Both the adh gene from Sulfolobus
      sp. strain RC3 and the alcohol dehydrogenase gene from Sulfolobus solfataricus
      (DSM 1617) were expressed at a high level in Escherichia coli, and the
      recombinant enzymes were purified, characterized, and compared. Only a few amino
      acid replacements were responsible for the different kinetic and physicochemical
      features investigated.

PMID- 8550435
TI  - AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of
      Escherichia coli multiple-antibiotic-resistance (Mar) mutants.
AB  - Multiple-antibiotic-resistance (Mar) mutants of Escherichia coli are resistant to
      a wide variety of antibiotics, and increased active efflux is known to be
      responsible for the resistance to some drugs. The identity of the efflux system,
      however, has remained unknown. By constructing an isogenic set of E. coli K-12
      strains, we showed that the marR1 mutation was incapable of increasing the
      resistance level in the absence of the AcrAB efflux system. This experiment
      identified the AcrAB system as the major pump responsible for making the Mar
      mutants resistant to many agents, including tetracycline, chloramphenicol,
      ampicillin, nalidixic acid, and rifampin.

PMID- 8550436
TI  - Differentially transcribed regions of Haloferax volcanii genome depending on the
      medium salinity.
AB  - To identify genomic regions involved in osmoregulation in the extremely
      halophilic archaeon Haloferax volcanii, we used a technique which involves
      hybridization of cDNAs obtained at different salinities against a cosmid library
      of the organism. Both low and high salt concentrations trigger differential
      expression; however, adaptation to low salinities seems to elicit a wider
      response. The presence of a large domain within the largest of the megaplasmids
      with a strong response to low salt concentrations is noteworthy.

PMID- 8550437
TI  - Identification of an anaerobically induced phosphoenolpyruvate-dependent fructose
      specific phosphotransferase system and evidence for the Embden-Meyerhof
      glycolytic pathway in the heterofermentative bacterium Lactobacillus brevis.
AB  - Heterofermentative gram-positive bacteria are believed to metabolize sugars
      exclusively via the pentose phosphoketolase pathway following uptake via
      sugar:cation symport. Here we show that anaerobic growth of one such bacterium,
      Lactobacillus brevis, in the presence of fructose induces the synthesis of a
      phosphotransferase system and glycolytic enzymes that allow fructose to be
      metabolized via the Embden-Meyerhof pathway.

PMID- 8550438
TI  - Isolation and structural analysis of polysaccharide containing galactofuranose
      from the cell walls of Bifidobacterium infantis.
AB  - We isolated cell wall polysaccharides (PS-1 and PS-2) from Bifidobacterium
      infantis Reuter ATCC 15697 and found that the backbone of PS-2 is-->3)-beta-D
      Galf-(1-->3)-alpha-D-Galp- (1-->in which beta-D-Galf and alpha-D-Galp are
      partially substituted at O-6 with beta-D-Glcp. This is the first report of the
      presence of this disaccharide backbone in a gram-positive bacterium; it resembles
      the O antigen of some bacteria.

PMID- 8550439
TI  - Autoregulation of iclR, the gene encoding the repressor of the glyoxylate bypass
      operon.
AB  - The aceBAK operon was partially induced by a multicopy plasmid which carried the
      promoter region of the gene which encodes its repressor, iclR. Gel shift and
      DNase I analyses demonstrated that IclR binds to its own promoter. Disruption of
      iclR increased the expression of an iclR::lacZ operon fusion. Although aceBAK and
      iclR are both regulated by IclR, aceBAK expression responds to the carbon source,
      while expression of iclR does not.

PMID- 8550440
TI  - mgpS, a complex regulatory locus involved in the transcriptional control of the
      puc and puf operons in Rhodobacter sphaeroides 2.4.1.
AB  - A new method has been developed in order to select mutants showing decreased puc
      operon transcription in Rhodobacter sphaeroides 2.4.1. A transcriptional fusion
      of a promoterless fragment derived from the sacB gene, encoding the levansucrase
      from Bacillus subtilis, to the upstream regulatory region of the puc operon has
      been constructed. With appropriate levels of exogenous sucrose, survivors of a
      sucrose killing challenge have been isolated. Subsequent analysis revealed the
      presence of both cis- and trans-acting "down" mutations in relation to puc operon
      expression. One of the trans-acting regulatory mutations was chosen for further
      study. The original mutation showed less than 2% of the level of puc operon
      transcription compared with the wild type under aerobic conditions and an 86%
      reduction under dark dimethyl sulfoxide conditions. This mutation can be
      complemented by a 3.9-kb BamHI DNA fragment derived from a cosmid contained
      within a genomic cosmid bank. DNA sequence analysis of this fragment revealed the
      presence of a 2.8-kb open reading frame, designated mgpS, which would encode a
      930-amino-acid protein. The N-terminal portion of the putative protein product
      presents homologies to proteins of the RNA helicase family. Disruption of the
      chromosomal mgpS resulted in decreased transcription of both puc and puf, while
      the presence of mgpS in multicopy in the wild type, 2.4.1., increased puc
      expression by a factor of 2 under aerobic conditions. Structural analysis of the
      mgpS locus revealed that expression of mgpS was likely to be complex. A smaller
      protein containing the 472 C-terminal amino acids of MgpS is able to act by
      itself as an activator of puc transcription and is expressed independently of the
      large open reading frame in which it is contained.

PMID- 8550441
TI  - Identification of a novel gene, pilZ, essential for type 4 fimbrial biogenesis in
      Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa produces type 4 fimbriae which
      promote adhesion to epithelial cells and are associated with a form of surface
      translocation called twitching motility. We have used transposon mutagenesis to
      identify loci required for fimbrial assembly or function by screening for mutants
      that lack the spreading colony morphology characteristic of twitching motility. A
      subset of these mutants is resistant to fimbria-specific phage. One of these
      mutants (R270) was found to contain a transposon insertion in a new gene, termed
      pilZ, which is located on chromosomal SpeI fragment I at about 40 min on the P.
      aeruginosa map, a position remote from other loci involved in fimbrial
      biogenesis. pilZ appears to be linked to and possibly forms an operon with a
      gene, holB*, which is homologous to the gene encoding the delta' subunit of
      Escherichia coli DNA polymerase III. The product of the pilZ gene is a protein of
      118 amino acids (predicted molecular weight, 12,895) which probably has a
      cytoplasmic location. PilZ appears to be a new class of protein which has not
      hitherto been represented in the sequence databases, and its function is unknown.
      Complementation studies indicate that pilZ is able to restore the expression of
      fimbriae on the surface of P. aeruginosa, as well as twitching motility and
      sensitivity to fimbria-specific phage when provided in trans to the R270 mutant.

PMID- 8550442
TI  - The ornithine decarboxylase gene odc is required for alcaligin siderophore
      biosynthesis in Bordetella spp.: putrescine is a precursor of alcaligin.
AB  - Chromosomal insertions defining Bordetella bronchiseptica siderophore phenotypic
      complementation group III mutants BRM3 and BRM5 were found to reside
      approximately 200 to 300 bp apart by restriction mapping of cloned genomic
      regions associated with the insertion markers. DNA hybridization analysis using
      B. bronchiseptica genomic DNA sequences flanking the cloned BRM3 insertion marker
      identified homologous Bordetella pertussis UT25 cosmids that complemented the
      siderophore biosynthesis defect of the group III B. bronchiseptica mutants.
      Subcloning and complementation analysis localized the complementing activity to a
      2.8-kb B. pertussis genomic DNA region. Nucleotide sequencing identified an open
      reading frame predicted to encode a polypeptide exhibiting strong similarity at
      the primary amino acid level with several pyridoxal phosphate-dependent amino
      acid decarboxylases. Alcaligin production was fully restored to group III mutants
      by supplementation of iron-depleted culture media with putrescine (1,4
      diaminobutane), consistent with defects in an ornithine decarboxylase activity
      required for alcaligin siderophore biosynthesis. Concordantly, the alcaligin
      biosynthesis defect of BRM3 was functionally complemented by the heterologous
      Escherichia coli speC gene encoding an ornithine decarboxylase activity. Enzyme
      assays confirmed that group III B. bronchiseptica siderophore-deficient mutants
      lack an ornithine decarboxylase activity required for the biosynthesis of
      alcaligin. Siderophore production by an analogous mutant of B. pertussis
      constructed by allelic exchange was undetectable. We propose the designation odc
      for the gene defined by these mutations that abrogate alcaligin siderophore
      production. Putrescine is an essential precursor of alcaligin in Bordetella spp.

PMID- 8550443
TI  - Reduced sulfur compound oxidation by Thiobacillus caldus.
AB  - The oxidation of reduced inorganic sulfur compounds was studied by using resting
      cells of the moderate thermophile Thiobacillus caldus strain KU. The oxygen
      consumption rate and total oxygen consumed were determined for the reduced sulfur
      compounds thiosulfate, tetrathionate, sulfur, sulfide, and sulfite in the absence
      and in the presence of inhibitors and uncouplers. The uncouplers 2,4
      dinitrophenol and carbonyl cyanide m-chlorophenyl-hydrazone had no affect on the
      oxidation of thiosulfate, suggesting that thiosulfate is metabolized
      periplasmically. In contrast, the uncouplers completely inhibited the oxidation
      of tetrathionate, sulfide, sulfur, and sulfite, indicating that these compounds
      are metabolized in the cytoplasm of T. caldus KU. N-Ethylmaleimide inhibited the
      oxidation of tetrathionate and thiosulfate at the stage of elemental sulfur,
      while 2-heptyl-4-hydroxyquinoline-N-oxide stopped the oxidation of thiosulfate,
      tetrathionate, and elemental sulfur at the stage of sulfite. The following
      intermediates in the oxidation of the sulfur compounds were found by using
      uncouplers and inhibitors: thiosulfate was oxidized to tetrathionate, elemental
      sulfur was formed during the oxidation of tetrathionate and sulfide, and sulfite
      was found as an intermediate of tetrathionate and sulfur metabolism. On the basis
      of these data we propose a model for the metabolism of the reduced inorganic
      sulfur compounds by T. caldus KU.

PMID- 8550444
TI  - The gntP gene of Escherichia coli involved in gluconate uptake.
AB  - The gntP gene, located between the fim and uxu loci in Escherichia coli K-12, has
      been cloned and characterized. Nucleotide sequencing of a region encompassing the
      gntP gene revealed an open reading frame of 447 codons with significant homology
      to the Bacillus subtilis gluconate permease. Northern (RNA) blotting indicated
      that the gntP gene was monocistronic and was transcribed as an mRNA with an
      apparent molecular size of 1.54 kb. The transcriptional start point was
      determined by primer extension analysis. The gntP gene was found to be under
      catabolite repression and was not induced by gluconate. Also, expression seemed
      to be stringently controlled. Several observations indicated that the GntP
      protein is an inner membrane protein; it contains characteristic membrane
      spanning regions and was isolated predominantly from the inner-membrane fraction
      of fractionated host cells. A topology analysis predicted a protein with 14
      membrane-spanning segments. The inability of a mutant strain to grow on gluconate
      minimal medium could be relieved by introduction of a plasmid encoding the gntP
      gene. Finally, the kinetics of GntP-mediated gluconate uptake were investigated,
      indicating an apparent Km for gluconate of 25 microM.

PMID- 8550445
TI  - A binding-lipoprotein-dependent oligopeptide transport system in Streptococcus
      gordonii essential for uptake of hexa- and heptapeptides.
AB  - Cells of the oral bacterium Streptococcus gordonii express three cytoplasmic
      membrane-bound lipoproteins with apparent molecular masses of 76 to 78 kDa that
      are the products of three genes (designated hppA, hppG, and hppH). The
      lipoproteins are immunologically cross-reactive, contain 60% or more identical
      amino acid residues, and are highly similar to the AmiA, AliA (PlpA), and AliB
      substrate-binding protein components of an oligopeptide permease in Streptococcus
      pneumoniae. Insertional inactivation of the hppA or hppH gene resulted in loss of
      the ability of S. gordonii cells to utilize specific peptides of five to seven
      amino acid residues for growth. An insertion within the COOH-terminal coding
      region of hppG that caused apparent truncation of the HppG polypeptide had a
      similar effect; however, S. gordonii mutants in which HppG polypeptide production
      was abolished were still able to grow on all oligopeptides tested. Inactivation
      of hppA gene (but not inactivation of the hppG or hppH gene) caused reduced
      growth rate of cells in complex medium, slowed the rate of development of
      competence for transformation, reduced the efficiency of transformation, and
      increased the resistance of cells to aminopterin. These results suggest that the
      formation of a solute-binding-protein complex consisting of at least the HppA and
      the HppH lipopolypeptides is necessary for binding and subsequent uptake of
      primarily hexa- or heptapeptides by a Hpp (Hexa-heptapeptide permease) system in
      S. gordonii. In addition, Hpp may play a role in the control of metabolic
      functions associated with the growth of streptococcal cells on complex nitrogen
      sources and with the development of competence.

PMID- 8550446
TI  - Host-mediated modification of PvuII restriction in Mycobacterium tuberculosis.
AB  - Restriction endonuclease PvuII plays a central role in restriction fragment
      length polymorphism analysis of Mycobacterium tuberculosis complex isolates with
      IS6110 as a genetic marker. We have investigated the basis for an apparent
      dichotomy in PvuII restriction fragment pattersn observed among strains of the M.
      tuberculosis complex. The chromosomal regions of two modified PvuII restriction
      sites, located upstream of the katG gene and downstream of an IS1081 insertion
      sequence, were studied in more detail. An identical 10-bp DNA sequence
      (CAGCTGGAGC) containing a PvuII site was found in both regions, and site-directed
      mutagenesis analysis revealed that this sequence was a target for modification.
      Strain-specific modification of PvuII sites was identified in DNA from over 80%
      of the nearly 800 isolates examined. Furthermore, the proportion of modifying and
      nonmodifying strains differs significantly from country to country.

PMID- 8550447
TI  - Comparative genome mapping of Pseudomonas aeruginosa PAO with P. aeruginosa C,
      which belongs to a major clone in cystic fibrosis patients and aquatic habitats.
AB  - A physical and genetic map was constructed for Pseudomonas aeruginosa C. Mainly,
      two-dimensional methods were used to place 47 SpeI, 8 PacI, 5 SwaI, and 4 I-CeuI
      sites onto the 6.5-Mb circular chromosome. A total of 21 genes, including the rrn
      operons and the origin of replication, were located on the physical map.
      Comparison of the physical and genetic map of strain C with that of the almost
      600-kb-smaller genome of P. aeruginosa reference strain PAO revealed conservation
      of gene order between the two strains. A large-scale mosaic structure which was
      due to insertions of blocks of new genetic elements which had sizes of 23 to 155
      kb and contained new SpeI sites was detected in the strain C chromosome. Most of
      these insertions were concentrated in three locations: two are congruent with the
      ends of the region rich in biosynthetic genes, and the third is located in the
      proposed region of the replication terminus. In addition, three insertions were
      scattered in the region rich in biosynthetic genes. The arrangement of the rrn
      operons around the origin of replication was conserved in C, PAO, and nine other
      examined independent strains.

PMID- 8550448
TI  - Amplification of a novel gene, sanA, abolishes a vancomycin-sensitive defect in
      Escherichia coli.
AB  - We have isolated an Escherichia coli gene which, when overexpressed, is able to
      complement the permeability defects of a vancomycin-susceptible mutant. This
      gene, designated sanA, is located at min 47 of the E. coli chromosome and codes
      for a 20-kDa protein with a highly hydrophobic amino-terminal segment. A strain
      carrying a null mutation of the sanA gene, transferred to the E. coli chromosome
      by homologous recombination, is perfectly viable, but after two generations at
      high temperature (43 degrees C), the barrier function of its envelope towards
      vancomycin is defective.

PMID- 8550449
TI  - D-histidine utilization in Salmonella typhimurium is controlled by the leucine
      responsive regulatory protein (Lrp).
AB  - A new class of D-histidine-utilizing mutants which carry mutations in the gene
      encoding the leucine-responsive regulatory protein (Lrp) has been identified in
      Salmonella typhimurium. The lrp mutations arise as suppressors of mutations in
      the genes encoding the histidine permease which drastically decrease the level of
      histidine transport activity. However, the suppressor effect is not exerted by
      elevating the level of the permease. Rather, the properties of the suppressor
      mutants are consistent with the notion that the parent permease mutants transport
      D-histidine at a low level and that in the suppressor mutants D-histidine is
      utilized effectively through elevated levels of racemization. The enzymatic
      activity of D-alanine dehydrogenase (Dad) is shown to be elevated in the
      suppressor mutants and is a possible pathway of D-histidine utilization. The
      suppressor mutations are located in the helix-turn-helix region of Lrp.

PMID- 8550450
TI  - Primary structure of cyanelle peptidoglycan of Cyanophora paradoxa: a prokaryotic
      cell wall as part of an organelle envelope.
AB  - The peptidoglycan layer surrounding the photosynthetic organelles (cyanelles) of
      the protist Cyanophora paradoxa is thought to be a relic of their cyanobacterial
      ancestors. The separation of muropeptides by gel filtration and reverse-phase
      high-performance liquid chromatography revealed four different muropeptide
      monomers. A number of muropeptides were identical in retention behavior to
      muropeptides of Escherichia coli, while others had remarkably long retention
      times with respect to their sizes, as indicated by gel filtration. Molecular mass
      determination by plasma desorption and matrix-assisted laser desorption
      ionization mass spectrometry showed that these unusual muropeptides had molecular
      masses greater by 112 Da or a multiple thereof than those of ones common to both
      species. Fast atom bombardment-tandem mass spectrometry of these reduced
      muropeptide monomers allowed the localization of the modification to D-glutamic
      acid. High-resolution fast atom bombardment-mass spectrometry and amino acid
      analysis revealed N-acetylputrescine to be the substituent (E. Pittenauer, E. R.
      Schmid, G. Allmaier, B. Pfanzagl, W. Loffelhardt, C. Quintela, M. A. de Pedro,
      and W. Stanek, Biol. Mass Spectrom. 22:524-536, 1993). In addition to the 4
      monomers already known, 8 dimers, 11 trimers, and 6 tetramers were characterized.
      An average glycan chain length of 51 disaccharide units was determined by the
      transfer of [U-14C]galactose to the terminal N-acetylglucosamine residues of
      cyanelle peptidoglycan. The muropeptide pattern is discussed with respect to
      peptidoglycan biosynthesis and processing.

PMID- 8550451
TI  - Characterization of the cdhD and cdhE genes encoding subunits of the
      corrinoid/iron-sulfur enzyme of the CO dehydrogenase complex from Methanosarcina
      thermophila.
AB  - The CO dehydrogenase enzyme complex from Methanosarcina thermophila contains a
      corrinoid/iron-sulfur enzyme composed of two subunits (delta and gamma). The cdhD
      and cdhE genes, which encode the delta and gamma subunits, respectively, were
      cloned and sequenced. The cdhD gene is upstream of and separated by 3 bp from
      cdhE. Both genes are preceded by apparent ribosome-binding sites. Northern (RNA)
      blot and primer extension analyses indicated that cdhD and cdhE are cotranscribed
      from a promoter located several kilobases upstream of cdhD. The putative CdhD and
      CdhE sequences are 37% identical to the sequences deduced from the genes encoding
      the beta and alpha subunits of the corrinoid/iron-sulfur enzyme from Clostridium
      thermoaceticum. The CdhE sequence had a four-cysteine motif with the potential to
      bind a 4Fe-4S cluster previously identified in the corrinoid/iron-sulfur enzyme
      by electron paramagnetic resonance spectroscopy. A T7 RNA polymerase/promoter
      system was used to produce CdhD and CdhE independently in Escherichia coli. The
      purified CdhD protein was reconstituted with hydroxocobalamin in the base-on
      configuration. The purified CdhE protein exhibited an Fe-S center and base-off
      cobalamin binding in which the benzimidazole base nitrogen atom was no longer a
      lower axial ligand to the cobalt atom.

PMID- 8550453
TI  - slpM, a gene coding for an "S-layer-like array" overexpressed in S-layer mutants
      of Thermus thermophilus HB8.
AB  - S-layer deletion mutants of Thermus thermophilus HB8 overproduce a regular array
      which surrounds groups of several cells. Averages of two-dimensional projections
      revealed a detailed architecture similar in general morphology and unit cell
      dimensions to that of the S-layer but having a different mass distribution. The
      structural components of these "S-layer-like arrays" are a group of three
      proteins of 52 (P52), 50 (P50), and 36 (P36) kDa, which are overexpressed in S
      layer mutants. These three proteins specifically bind antibodies against P52,
      suggesting that the smaller proteins correspond to fragments derived from P52.
      This hypothesis was demonstrated by the identity of the trypsin digestion
      products of P52 and P50. The gene slpM, responsible for the synthesis of P52, was
      cloned by using synthetic oligonucleotides designed from partial amino acid
      sequences of P52 and P50. When slpM was expressed in Escherichia coli, proteins
      specifically recognized by anti-P52 antiserum whose electrophoretic mobilities
      were similar to those of P52 and P36 were detected. The sequence of slpM revealed
      the existence of an open reading frame in which the amino termini of P52, P50,
      and P36 were identified. The unprocessed product of slpM is a 469-amino-acid-long
      polypeptide whose theoretical M(r) (52,131) was in good agreement with the
      electrophoretic mobility of P52. The properties deduced for the product of slpM
      are very different from those of any S-layer protein so far sequenced. The
      possible roles of SlpM in wild-type cells are discussed.

PMID- 8550452
TI  - Deduced amino acid sequence, functional expression, and unique enzymatic
      properties of the form I and form II ribulose bisphosphate carboxylase/oxygenase
      from the chemoautotrophic bacterium Thiobacillus denitrificans.
AB  - The cbbL cbbS and cbbM genes of Thiobacillus denitrificans, encoding form I and
      form II ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO), respectively,
      were found to complement a RubisCO-negative mutant of Rhodobacter sphaeroides to
      autotrophic growth. Endogenous T. denitrificans promoters were shown to function
      in R. sphaeroides, resulting in high levels of cbbL cbbS and cbbM expression in
      the R. sphaeroides host. This expression system provided high levels of both T.
      denitrificans enzymes, each of which was highly purified. The deduced amino acid
      sequence of the form I enzyme indicated that the large subunit was closely
      homologous to previously sequenced form I RubisCO enzymes from sulfur-oxidizing
      bacteria. The form I T. denitrificans enzyme possessed a very low substrate
      specificity factor and did not exhibit fallover, and yet this enzyme showed a
      poor ability to recover from incubation with ribulose 1,5-bisphosphate. The
      deduced amino acid sequence of the form II T. denitrificans enzyme resembled
      those of other form II RubisCO enzymes. The substrate specificity factor was
      characteristically low, and the lack of fallover and the inhibition by ribulose
      1,5-bisphosphate were similar to those of form II RubisCO obtained from nonsulfur
      purple bacteria. Both form I and form II RubisCO from T. denitrificans possessed
      high KCO2 values, suggesting that this organism might suffer in environments
      containing low levels of dissolved CO2. These studies present the initial
      description of the kinetic properties of form I and form II RubisCO from a
      chemoautotrophic bacterium that synthesizes both types of enzyme.

PMID- 8550454
TI  - Bacteriocin small of Rhizobium leguminosarum belongs to the class of N-acyl-L
      homoserine lactone molecules, known as autoinducers and as quorum sensing co
      transcription factors.
AB  - Small bacteriocin was isolated from the culture broth of the gram-negative
      bacterium Rhizobium leguminosarum, which forms symbiotic nitrogen-fixing root
      nodules on a number of leguminous plants. The structure of the molecule was
      elucidated by spectroscopic methods and identified as N-(3R-hydroxy-7-cis
      tetradecanoyl)-L-homoserine lactone. The absolute configuration of both
      asymmetric carbon atoms in the molecule was determined by the use of the chiral
      solvating agents S-(+)- and R-(-)-2,2,2-trifluoro-1-(9-anthryl)-ethanol. small
      bacteriocin is structurally related to the quorum sensing co-transcription
      factors for genes from other bacteria such as Vibrio fischeri, Pseudomonas
      aeruginosa, Erwinia carotovora, and Agrobacterium tumefaciens which are involved
      in animal-microbe or plant-microbe interactions. The mechanism of regulation of
      such interactions by this kind of co-transcription factors is still unknown in R.
      leguminosarum.

PMID- 8550455
TI  - Cell-to-cell signaling in the symbiotic nitrogen-fixing bacterium Rhizobium
      leguminosarum: autoinduction of a stationary phase and rhizosphere-expressed
      genes.
AB  - The Sym plasmid pRL1JI encodes functions for the formation of nitrogen-fixing pea
      root nodules by Rhizobium leguminosarum. Some of the nodulation genes are
      involved in recognition of chemical signals produced by the plant root, and
      others are required for production of chemical signals recognized by the plant.
      pRL1JI also contains a regulatory gene, rhiR, that is homologous to luxR, the
      transcriptional activator of luminescence genes in Vibrio fischeri. LuxR requires
      a signal compound, an autoinducer, for its activity. We have identified an R.
      leguminosarum autoinducer that, together with RhiR, is required to activate both
      the rhizosphere-expressed rhiABC operon and a growth-inhibiting function encoded
      by pRL1JI. This intercellular signal is an N-acylated homoserine lactone
      structurally related to the V. fischeri and other autoinducers. These findings
      indicate a new level of intercellular communication in root nodule formation.

PMID- 8550456
TI  - Identification of a region of genetic variability among Bacillus anthracis
      strains and related species.
AB  - The identification of a region of sequence variability among individual isolates
      of Bacillus anthracis as well as the two closely related species, Bacillus cereus
      and Bacillus mycoides, has made a sequence-based approach for the rapid
      differentiation among members of this group possible. We have identified this
      region of sequence divergence by comparison of arbitrarily primed (AP)-PCR
      "fingerprints" generated by an M13 bacteriophage-derived primer and sequencing
      the respective forms of the only polymorphic fragment observed. The 1,480-bp
      fragment derived from genomic DNA of the Sterne strain of B. anthracis contained
      four consecutive repeats of CAATATCAACAA. The same fragment from the Vollum
      strain was identical except that two of these repeats were deleted. The Ames
      strain of B. anthracis differed from the Sterne strain by a single-nucleotide
      deletion. More than 150 nucleotide differences separated B. cereus and B.
      mycoides from B. anthracis in pairwise comparisons. The nucleotide sequence of
      the variable fragment from each species contained one complete open reading frame
      (ORF) (designated vrrA, for variable region with repetitive sequence), encoding a
      potential 30-kDa protein located between the carboxy terminus of an upstream ORF
      (designated orf1) and the amino terminus of a downstream ORF (designated lytB).
      The sequence variation was primarily in vrrA, which was glutamine- and proline
      rich (30% of total) and contained repetitive regions. A large proportion of the
      nucleotide substitutions between species were synonymous. vrrA has 35% identity
      with the microfilarial sheath protein shp2 of the parasitic worm Litomosoides
      carinii.

PMID- 8550457
TI  - Induction of synthesis of tetrahydropyrimidine derivatives in Streptomyces
      strains and their effect on Escherichia coli in response to osmotic and heat
      stress.
AB  - The metabolic responses of a number of Streptomyces strains to osmotic and heat
      stress were studied by 13C nuclear magnetic resonance spectroscopy. During cell
      growth in a chemically defined medium supplemented with 0.5 M NaCl,
      tetrahydropyrimidine derivatives (THPs), 2-methyl-4-carboxy-5-hydroxy-3,4,5,6
      tetrahydropyrimidine [THP(A)] and, to a lesser extent, 2-methyl-4-carboxy-3,4,5,6
      tetrahydropyrimidine [THP(B)], were found to accumulate in a significant amount
      in all bacteria examined. In addition, when the growth temperature was shifted
      from 30 to 39 degrees C, the intracellular concentration of THP(A) increased
      significantly. Moreover, exogenously provided THP(A) or THP(B) or both reversed
      inhibition of Escherichia coli growth caused by osmotic stress and increased
      temperature. Although the ability of Streptomyces strains to tolerate high
      concentrations of NaCl is well known, very little is known about the
      osmoregulatory strategy in Streptomyces strains. Similarly, the mechanism by
      which compatible solutes accumulate in a variety of microorganisms is not
      understood. Our findings suggest the possibility of a novel mechanism of
      protection of DNA against salt and heat stresses involving the THPs.

PMID- 8550458
TI  - Altered lipopolysaccharide characteristic of the I69 phenotype in Haemophilus
      influenzae results from mutations in a novel gene, isn.
AB  - The 169 phenotype of Haemophilus influenzae results from a mutation leading to a
      lipopolysaccharide molecule consisting only of lipid A and a single
      phosphorylated 2-keto-3-deoxyoctulosonic acid residue. In this paper we describe
      the identification of a gene which, when mutated, results in the 169 phenotype.
      We have named the gene isn. The predicted amino acid sequence of Isn is
      homologous to the product of the lmbN gene involved in the biosynthesis of the
      sugar-containing antibiotic lincomycin by Streptomyces lincolnensis. lsn is
      situated between two loci that are homologous to the dpp and art periplasmic
      permease systems in Escherichia coli. Northern (RNA) blot and primer extension
      analyses reveal that isn is transcribed as a monocistronic mRNA. Potential
      functions of Isn protein are discussed.

PMID- 8550459
TI  - Ammonium/urea-dependent generation of a proton electrochemical potential and
      synthesis of ATP in Bacillus pasteurii.
AB  - The influence of ammonium and urea on the components of the proton
      electrochemical potential (delta p) and de novo synthesis of ATP was studied with
      Bacillus pasteurii ATCC 11859. In washed cells grown at high urea concentrations,
      a delta p of -56 +/- 29 mV, consisting of a membrane potential (delta psi) of 
      228 +/- 19 mV and of a transmembrane pH gradient (delta pH) equivalent to 172 +/-
      38 mV, was measured. These cells contained only low amounts of potassium, and the
      addition of ammonium caused an immediate net decrease of both delta psi and delta
      pH, resulting in a net increase of delta p of about 49 mV and de novo synthesis
      of ATP. Addition of urea and its subsequent hydrolysis to ammonium by the
      cytosolic urease also caused an increase of delta p and ATP synthesis; a net
      initial increase of delta psi, accompanied by a slower decrease of delta pH in
      this case, was observed. Cells grown at low concentrations of urea contained high
      amounts of potassium and maintained a delta p of -113 +/- 26 mV, with a delta psi
      of -228 +/- 22 mV and a delta pH equivalent to 115 +/- 20 mV. Addition of
      ammonium to such cells resulted in the net decrease of delta psi and delta pH
      without a net increase in delta p or synthesis of ATP, whereas urea caused an
      increase of delta p and de novo synthesis of ATP, mainly because of a net
      increase of delta psi. The data reported in this work suggest that the ATP
      generating system is coupled to urea hydrolysis via both an alkalinization of the
      cytoplasm by the ammonium generated in the urease reaction and a net increase of
      delta psi that is probably due to an efflux of ammonium ions. Furthermore, the
      findings of this study show that potassium ions are involved in the regulation of
      the intracellular pH and that ammonium ions may functionally replace potassium to
      a certain extent in reducing the membrane potential and alkalinizing the
      cytoplasm.

PMID- 8550460
TI  - Characterization of genes required for pilus expression in Pseudomonas syringae
      pathovar phaseolicola.
AB  - Nonpiliated, phage phi 6-resistant mutants of Pseudomonas syringae pv.
      phaseolicola were generated by Tn5 transposon mutagenesis. A P. syringae pv.
      phaseolicola LR700 cosmid library was screened with Tn5-containing EcoRI
      fragments cloned from nonpiliated mutants. The cosmid clone pVK253 complemented
      the nonpiliated mutant strain HB2.5. A 3.8-kb sequenced region spanning the Tn5
      insertion site contained four open reading frames. The transposon-inactivated
      gene, designated pilP, is 525 bp long, potentially encoding a 19.1-kDa protein
      precursor that contains a typical membrane lipoprotein leader sequence.
      Generation of single mutations in each of the three remaining complete open
      reading frames by marker exchange also resulted in a nonpiliated phenotype.
      Expression of this gene region by the T7 expression system in Escherichia coli
      resulted in four polypeptides of approximately 39, 26, 23, and 18 kDa, in
      agreement with the sizes of the open reading frames. The three genes upstream of
      pilP were designated pilM (39 kDa), pilN (23 kDa), and pilO (26 kDa). The
      processing of the PilP precursor into its mature form was shown to be inhibited
      by globomycin, a specific inhibitor of signal peptidase II. The gene region
      identified shows a high degree of homology to a gene region reported to be
      required for Pseudomonas aeruginosa type IV pilus production.

PMID- 8550461
TI  - Characterization of the sar locus and its interaction with agr in Staphylococcus
      aureus.
AB  - The expression of cell wall and extracellular proteins in Staphylococcus aureus
      is controlled by global regulatory systems, including sar and agr. We have
      previously shown that a transposon insertion into the 372-bp sarA gene within the
      sar locus resulted in decreased expression of several extracellular and cell wall
      proteins (A. L. Cheung and S. J. Projan, J. Bacteriol. 176:4168-4172, 1994). In
      this study, Northern (RNA blot) analysis with a 732-bp sarA probe indicated that
      two major transcripts (0.56 and 1.2 kb) were absent in the sar mutant compared
      with the parental strain RN6390. Additional transcriptional studies revealed that
      the sarA gene is encoded within the 0.56-kg transcript. Notably, a plasmid
      carrying the sarA gene together with a 1.2-kb upstream fragment (1.7 kb total)
      was able to reestablish the 1.2-kb transcript in the mutant. Although
      reconstitution of the parental phenotype by the sarA gene was incomplete, the
      introduction of a plasmid carrying the 1.7-kb fragment to the mutant restored the
      parental phenotype. Transcription of RNAII and RNAIII, which encode the
      structural and regulatory genes of agr, respectively, was diminished in the
      mutant but restored to wild-type levels by complementation with the 1.7-kb
      fragment. In gel shift assays, cell extracts of this clone were able to retard
      the mobility of a labeled RNAII promoter probe but not an RNAIII promoter
      element. These data suggest that sarA and the adjacent upstream DNA are essential
      to the expression of a DNA-binding protein(s) with specificity for the RNAII
      promoter, thereby controlling agr-related transcription.

PMID- 8550462
TI  - Dra-nupC-pdp operon of Bacillus subtilis: nucleotide sequence, induction by
      deoxyribonucleosides, and transcriptional regulation by the deoR-encoded DeoR
      repressor protein.
AB  - The genes encoding deoxyriboaldolase (dra), nucleoside uptake protein (nupC), and
      pyrimidine nucleoside sequences were determined. Sequence analysis showed that
      the genes were localized immediately downstream of the hut operon. Insertional
      gene disruption studies indicated that the three genes constitute an operon with
      the gene order dra-nupC-pdp. A promoter mapping immediately upstream of the dra
      gene was identified, and downstream of the pdp gene the nucleotide sequence
      indicated the existence of a factor-independent transcription terminator
      structure. In wild-type cells growing in succinate minimal medium, the pyrimidine
      nucleoside phosphorylase and deoxyriboaldolase levels were five- to eightfold
      higher in the presence of thymidine and fourfold higher in the presence of
      deoxyadenosine. By the use of lacZ fusions, the regulation was found to be at the
      level of transcription. The operon expression was subject to glucose repression.
      Upstream of the dra gene an open reading frame of 313 amino acids was identified.
      Inactivation of this gene led to an approximately 10-fold increase in the levels
      of deoxyriboaldolase and pyrimidine nucleoside phosphorylase, and no further
      induction was seen upon the addition of deoxyribonucleosides. The upstream gene
      most likely encodes the regulator for the dra-nupC-pdp operon and was designated
      deoR (stands for deoxyribonucleoside regulator).

PMID- 8550463
TI  - Conserved cis-acting promoter elements are required for density-dependent
      transcription of Agrobacterium tumefaciens conjugal transfer genes.
AB  - Ti plasmids of Agrobacterium tumefaciens, in addition to transferring oncogenic
      DNA to the nuclei of infected plant cells, can conjugally transfer between
      agrobacteria. Conjugation of wide-host-range octopine-type Ti plasmids requires a
      tumor-released arginine derivative called octopine. Octopine stimulates
      expression of the traR gene, whose product directly activates other tra genes in
      the presence of an acylated homoserine lactone called Agrobacterium autoinducer
      (AAI). We have localized the transcription starts of three tra promoters and find
      conserved elements (tra boxes) at virtually identical positions upstream of each
      promoter. Disruption of these tra boxes abolished induction of each promoter.
      Deletion analysis of the traI promoter indicates that tra boxes are the only
      upstream elements required for transcriptional activation. Since Ti plasmid donor
      cells both produce and respond to AAI, we tested whether expression of tra
      promoters was enhanced by high concentrations of bacteria. Both tra gene
      expression and conjugation itself were strongly stimulated either by high donor
      densities or by exogenous AAI.

PMID- 8550464
TI  - Cell wall sorting of lipoproteins in Staphylococcus aureus.
AB  - Many surface proteins are thought to be anchored to the cell wall of gram
      positive organisms via their C termini, while the N-terminal domains of these
      molecules are displayed on the bacterial surface. Cell wall anchoring of surface
      proteins in Staphylococcus aureus requires both an N-terminal leader peptide and
      a C-terminal cell wall sorting signal. By fusing the cell wall sorting of protein
      A to the C terminus of staphylococcal beta-lactamase, we demonstrate here that
      lipoproteins can also be anchored to the cell wall of S. aureus. The topology of
      cell wall-anchored beta-lactamase is reminiscent of that described for Braun's
      murein lipoprotein in that the N terminus of the polypeptide chain is membrane
      anchored whereas the C-terminal end is tethered to the bacterial cell wall.

PMID- 8550465
TI  - Characterization of the Erwinia chrysanthemi osmoprotectant transporter gene
      ousA.
AB  - Growth of Erwinia chrysanthemi in media of elevated osmolarity can be achieved by
      the uptake and accumulation of various osmoprotectants. This study deals with the
      cloning and sequencing of the ousA gene-encoded osmoprotectant uptake system A
      from E. chrysanthemi 3937. OusA belongs to the superfamily of solute ion
      cotransporters. This osmotically inducible system allows the uptake of glycine
      betaine, proline, ectoine, and pipecolic acid and presents strong similarities in
      nucleotide sequence and protein function with the proline/betaine porter of
      Escherichia coli encoded by proP. The control of ousA expression is clearly
      different from that of proP. It is induced by osmotic strength and repressed by
      osmoprotectants. Its expression in E. coli is controlled by H-NS and is rpoS
      dependent in the exponential phase but unaffected by the stationary phase.

PMID- 8550466
TI  - Identification of the surface-exposed lipids on the cell envelopes of
      Mycobacterium tuberculosis and other mycobacterial species.
AB  - The surface-exposed lipids of Mycobacterium tuberculosis, Mycobacterium avium,
      Mycobacterium kansasii, Mycobacterium gastri, Mycobacterium smegmatis, and
      Mycobacterium aurum were isolated by gentle mechanical treatment of cells with
      glass beads. Analysis of the exposed lipids demonstrated a selective location of
      classes of ubiquitous lipids on the surfaces of mycobacteria. While
      phosphatidylethanolamine and phosphatidylinositol mannosides were exposed in all
      the species examined, dimycoloyl trehalose ("cord factor") was identified in the
      surface components of M. aurum only. Furthermore, monomycoloyl trehaloses and
      triacylglycerides were identified in the surface-exposed lipids of M. avium and
      M. smegmatis but not in those of the other mycobacterial species examined. The
      species- and type-species specific lipids were present on the mycobacterial cell
      surface: phenolic glycolipids, dimycocerosates of phthiocerols, and
      lipooligosaccharides were identified in the surface-exposed materials of M.
      tuberculosis (Canetti), M. kansasii, and M. gastri, whereas glycopeptidolipids
      were identified in the outermost lipid constituents of M. avium and M. smegmatis.
      This difference in the surface exposure of lipids of various mycobacterial
      species may reflect differences in their cell envelope organizations. Brief
      treatments of M. tuberculosis with Tween 80 prior to the use of glass beads led
      to erosion of regions of the capsule to expose gradually both cord factor and
      other lipids on the cell surface of the tubercle bacillus, demonstrating that the
      latter lipids are buried more deeply in the cell envelope and leading to the
      proposal of a scheme for the location of the capsular lipids of the tubercle
      bacillus.

PMID- 8550467
TI  - Transcriptional regulation of the sucrase gene of Staphylococcus xylosus by the
      repressor ScrR.
AB  - In Staphylococcus xylosus, scrB is one of two genes necessary for sucrose
      utilization. It encodes a sucrase that hydrolyzes intracellular sucrose-6
      phosphate generated by the uptake of sucrose via the sucrose-specific enzyme II
      of the phosphotransferase system, the gene product of scrA. ScrB sucrase activity
      is inducible by the presence of sucrose in the culture medium. Primer extension
      experiments demonstrated that the observed regulation is achieved at the level of
      scrB transcription initiation. The protein mediating sucrose-specific regulation
      of scrB was found to be encoded immediately upstream of the sucrase gene. The
      nucleotide sequence of the regulatory gene scrR comprises an open reading frame
      that specifies a protein of 35.8 kDa. This protein exhibits similarity to
      transcriptional regulators of the GalR-LacI family. Inactivation of the scrR
      reading frame in the genome of S. xylosus led to the constitutive expression of
      scrB at a high level, identifying ScrR as a repressor of transcription. Sucrose
      specific regulation of scrB was also lost upon deletion of 4 bp of a palindromic
      sequence (OB) covering positions +6 to +21 downstream of the scrB transcriptional
      start site. These results suggested a direct interaction of the ScrR repressor
      and the operator OB. Accordingly, a fusion protein consisting of the maltose
      binding protein of Escherichia coli and the ScrR protein was able to interact
      with an scrB promoter fragment in gel mobility shift experiments but failed to
      bind an scrB fragment carrying the 4-bp deletion derivative of OB. An scrR
      promoter fragment, which dose not contain a sequence resembling OB, was not
      shifted by the fusion protein. This result corroborates scrR primer extension
      analyses showing that transcription of the repressor gene itself is not
      regulated. Therefore, the sucrase gene operator OB is the target sequence through
      which the ScrR protein exerts its negative effect on transcription initiation. In
      the promoter region of scrA, the gene essential for sucrose transport, two
      palindromic sequences that are similar to the scrB operator are found. Their
      presence in scrA suggests that ScrR controls a sucrose-specific regulon in S.
      xylosus.

PMID- 8550468
TI  - Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP
      protease.
AB  - In Escherichia coli, starvation (stationary-phase)-mediated differentiation
      involves 50 or more genes and is triggered by an increase in cellular sigma s
      levels. Western immunoblot analysis showed that in mutants lacking the protease
      ClpP or its cognate ATPase-containing subunit ClpX, sigma s levels of exponential
      phase cells increased to those of stationary-phase wild-type cells. Lack of other
      potential partners of ClpP, i.e., ClpA or ClpB, or of Lon protease had no effect.
      In ClpXP-proficient cells, the stability of sigma s increased markedly in
      stationary-phase compared with exponential-phase cells, but in ClpP-deficient
      cells, sigma s became virtually completely stable in both phases. There was no
      decrease in ClpXP levels in stationary-phase wild-type cells. Thus, sigma s
      probably becomes more resistant to this protease in stationary phase. The
      reported sigma s-stabilizing effect of the hns mutation also was not due to
      decreased protease levels. Studies with translational fusions containing
      different lengths of sigma s coding region suggest that amino acid residues 173
      to 188 of this sigma factor may directly or indirectly serve as at least part of
      the target for ClpXP protease.

PMID- 8550469
TI  - HKR1 encodes a cell surface protein that regulates both cell wall beta-glucan
      synthesis and budding pattern in the yeast Saccharomyces cerevisiae.
AB  - We previously isolated the Saccharomyces cerevisiae HKR1 gene that confers on S.
      cerevisiae cells resistance to HM-1 killer toxin secreted by Hansenula mrakii (S.
      Kasahara, H. Yamada, T. Mio, Y. Shiratori, C. Miyamoto, T. Yabe, T. Nakajima, E.
      Ichishima, and Y. Furuichi, J. Bacteriol. 176:1488-1499, 1994). HKR1 encodes a
      type 1 membrane protein that contains a calcium-binding consensus sequence (EF
      hand motif) in the cytoplasmic domain. Although the null mutation of HKR1 is
      lethal, disruption of the 3' part of the coding region, which would result in
      deletion of the cytoplasmic domain of Hkr1p, did not affect the viability of
      yeast cells. This partial disruption of HKR1 significantly reduced beta-1,3
      glucan synthase activity and the amount of beta-1,3-glucan in the cell wall and
      altered the axial budding pattern of haploid cells. Neither chitin synthase
      activity nor chitin content was significantly affected in the cells harboring the
      partially disrupted HKR1 allele. Immunofluorescence microscopy with an antibody
      raised against Hkr1p expressed in Escherichia coli revealed that Hkr1p was
      predominantly localized on the cell surface. The cell surface localization of
      Hkr1p required the N-terminal signal sequence because the C-terminal half of
      Hkr1p was detected uniformly in the cells. These results demonstrate that HKR1
      encodes a cell surface protein that regulates both cell wall beta-glucan
      synthesis and budding pattern and suggest that bud site assembly is somehow
      related to beta-glucan synthesis in S. cerevisiae.

PMID- 8550470
TI  - Thermostable chemotaxis proteins from the hyperthermophilic bacterium Thermotoga
      maritima.
AB  - An expressed sequence tag homologous to cheA was previously isolated by random
      sequencing of Thermotoga maritima cDNA clones (C. W. Kim, P. Markiewicz, J. J.
      Lee, C. F. Schierle, and J. H. Miller, J. Mol. Biol. 231: 960-981, 1993).
      Oligonucleotides complementary to this sequence tag were synthesized and used to
      identify a clone from a T. maritima lambda library by using PCR. Two partially
      overlapping restriction fragments were subcloned from the lambda clone and
      sequenced. The resulting 5,251-bp sequence contained five open reading frames,
      including cheA, cheW, and cheY. In addition to the chemotaxis genes, the fragment
      also encodes a putative protein isoaspartyl methyltransferase and an open reading
      frame of unknown function. Both the cheW and cheY genes were individually cloned
      into inducible Escherichia coli expression vectors. Upon induction, both proteins
      were synthesized at high levels. T. maritima CheW and CheY were both soluble and
      were easily purified from the bulk of the endogenous E. coli protein by heat
      treatment at 80 degrees C for 10 min. CheY prepared in this way was shown to be
      active by the demonstration of Mg(2+)-dependent autophosphorylation with
      [32P]acetyl phosphate. In E. coli, CheW mediates the physical coupling of the
      receptors to the kinase CheA. The availability of a thermostable homolog of CheW
      opens the possibility of structural characterization of this small coupling
      protein, which is among the least well characterized proteins in the bacterial
      chemotaxis signal transduction pathway.

PMID- 8550471
TI  - Cloning and characterization of a gene (msdA) encoding methylmalonic acid
      semialdehyde dehydrogenase from Streptomyces coelicolor.
AB  - A homolog of the mmsA gene of Pseudomonas aeruginosa, which encodes methylmalonic
      acid semialdehyde dehydrogenase (MSDH) and is involved in valine catabolism in
      pseudomonads and mammals, was cloned and sequenced from Streptomyces coelicolor.
      Of the two open reading frames (ORFs) found, which are convergently transcribed
      and separated by a 62-nucleotide noncoding region, the deduced amino acid
      sequence of the msdA ORF (homologous to mmsA) is similar to a variety of
      prokaryotic and eukaryotic aldehyde dehydrogenases that utilize NAD+,
      particularly to the MmsA protein from P. aeruginosa. No significant similarity
      was found between the deduced product of ORF1 and known proteins in the
      databases. An S. coelicolor msdA mutant, constructed by insertion of a hygromycin
      resistance gene (hyg) into the msdA coding region, lost the MSDH activity and the
      ability to grow in a minimal medium with valine or isobutyrate as the sole carbon
      source but grew on propionate. The msdA::hyg mutation was complemented by
      introduction of the msdA gene on a plasmid. When the S. coelicolor msdA gene was
      overexpressed in Escherichia coli under the control of the T7 promoter, a protein
      of 51-kDa, corresponding to the approximate mass of the predicted S. coelicolor
      msdA product (52.6 kDa), and specific MSDH activity were detected. These results
      strongly suggest that msdA indeed encodes the MSDH that is involved in valine
      catabolism in S. coelicolor.

PMID- 8550472
TI  - Ferric rhizoferrin uptake into Morganella morganii: characterization of genes
      involved in the uptake of a polyhydroxycarboxylate siderophore.
AB  - Iron uptake in Morganella morganii, mediated by the fungal siderophore
      rhizoferrin, was studied. A Mud1 insertion mutant devoid of growth on ferric
      rhizoferrin was complemented by a chromosomal DNA fragment of M. morganii that
      encoded an outer membrane protein and a periplasmic protein named RumA and RumB
      (for rhizoferrin uptake into Morganella spp.), respectively. rumA and rumB have
      the same transcription polarity and are probably cotranscribed from an iron
      regulated promoter upstream of rumA. A predicted Fur regulatory sequence upstream
      of rumA was confirmed by the Fur titration assay. At the N terminus of RumA, a
      putative TonB box contains a proline residue that inactivates TonB-dependent
      receptors and colicins when introduced at the same position into TonB boxes of
      Escherichia coli. Analysis of a 10-kb sequence flanking rumA and rumB on both
      sides revealed seven additional open reading frames for which no role in ferric
      rhizoferrin uptake could be discerned. Thus, rumA and rumB, both essential for
      transport of this siderophore, form an isolated operon. Additional genes required
      for ferric rhizoferrin translocation across the cytoplasmic membrane must map at
      sites distinct from rumA and rumB. Transport studies revealed that both 55Fe3+
      and [3H]ketorhizoferrin are incorporated by M. morganii, demonstrating that
      rhizoferrin serves as a true iron carrier.

PMID- 8550473
TI  - Coenzyme F390 synthetase from Methanobacterium thermoautotrophicum Marburg
      belongs to the superfamily of adenylate-forming enzymes.
AB  - Depending on the reduction-oxidation state of the cell, some methanogenic
      bacteria synthesize or hydrolyze 8-hydroxyadenylylated coenzyme F420 (coenzyme
      F390). These two reactions are catalyzed by coenzyme F390 synthetase and
      hydrolase, respectively. To gain more insight into the mechanism of the former
      reaction, coenzyme F390 synthetase from Methanobacterium thermoautotrophicum
      Marburg was purified 89-fold from cell extract to a specific activity of 0.75
      mumol.min-1.mg of protein-1. The monomeric enzyme consisted of a polypeptide with
      an apparent molecular mass of 41 kDa as determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. ftsA, the gene encoding coenzyme F390
      synthetase, was cloned and sequenced. It encoded a protein of 377 amino acids
      with a predicted M(r) of 43,280. FtsA was found to be similar to domains found in
      the superfamily of peptide synthetases and adenylate-forming enzymes. FtsA was
      most similar to gramicidin S synthetase II (67% similarity in a 227-amino-acid
      region) and sigma-(L-alpha-aminoadipyl)-L-cysteine-D-valine synthetase (57%
      similarity in a 193-amino-acid region). Coenzyme F390 synthetase, however, holds
      an exceptional position in the superfamily of adenylate-forming enzymes in that
      it does not activate a carboxyl group of an amino or hydroxy acid but an aromatic
      hydroxyl group of coenzyme F420.

PMID- 8550474
TI  - Two distinct loci affecting conversion to mucoidy in Pseudomonas aeruginosa in
      cystic fibrosis encode homologs of the serine protease HtrA.
AB  - Conversion to a mucoid, exopolysaccharide alginate-overproducing phenotype in
      Pseudomonas aeruginosa is associated with chronic respiratory infections in
      cystic fibrosis. Mucoidy is caused by muc mutations that derepress the
      alternative sigma factor AlgU, which in turn activates alginate biosynthetic and
      ancillary regulatory genes. Here we report the molecular characterization of two
      newly identified genes, algW and mucD, that affect expression of mucoidy. The
      algW gene, mapping at 69 min, was isolated on the basis of its ability to
      suppress mucoidy and reduce transcription of the alginate biosynthetic gene algD.
      The predicted primary structure of AlgW displayed similarity to HtrA (DegP), a
      serine protease involved in proteolysis of abnormal proteins and required for
      resistance to oxidative and heat stress in enteric bacteria. Inactivation of algW
      on the chromosome of the wild-type nonmucoid strain PAO1 caused increased
      sensitivity to heat, H2O2, and paraquat, a redox cycling compound inducing
      intracellular levels of superoxide. This mutation also permitted significant
      induction of alginate production in the presence of subinhibitory concentrations
      of paraquat. Two new genes, mucC and mucD, were identified immediately downstream
      of the previously characterized portion (algU mucA mucB) of the gene cluster at
      67.5 min encoding the alternative sigma factor AlgU and its regulators.
      Interestingly, the predicted gene product of mucD also showed similarities to
      HtrA. Inactivation of mucD on the PAO1 chromosome resulted in conversion to the
      mucoid phenotype. The mutation in mucD also caused increased sensitivity to H2O2
      and heat killing. However, in contrast to algW mutants, no increase in
      susceptibility to paraquat was observed in mucD mutants. These findings indicate
      that algW and mucD play partially overlapping but distinct roles in P. aeruginosa
      resistance to reactive oxygen intermediates and heat. In addition, since
      mutations in mucD and algW cause conversion to mucoidy or lower the threshold for
      its induction by reactive oxygen intermediates, these factors may repress
      alginate synthesis either directly by acting on AlgU or its regulators or
      indirectly by removing physiological signals that may activate this stress
      response system.

PMID- 8550476
TI  - Analysis of the Staphylococcus epidermidis genes epiF, -E, and -G involved in
      epidermin immunity.
AB  - The lantibiotic epidermin is produced by Staphylococcus epidermidis Tu3298. The
      known genes involved in epidermin biosynthesis and regulation are organized as
      operons (epiABCD and epiQP) that are encoded on the 54-kb plasmid pTu32. Here we
      describe the characterization of a DNA region that mediates immunity and
      increased epidermin production, located upstream of the structural gene epiA. The
      sequence of a 2.6-kb DNA fragment revealed three open reading frames, epiF, -E,
      and -G, which may form an operon. In the cloning host Staphylococcus carnosus,
      the three genes mediated an increased tolerance to epidermin, and the highest
      level of immunity (sevenfold) was achieved with S. carnosus carrying epiFEG and
      epiQ. The promoter of the first gene, epiF, responded to the activator protein
      EpiQ and contained a palindromic sequence similar to the EpiQ binding site of the
      epiA promoter, which is also activated by EpiQ. Inactivation of epiF, -E, or -G
      resulted in the complete loss of the immunity phenotype. An epidermin-sensitive
      S. epidermidis Tu3298 mutant was complemented by a DNA fragment containing all
      three genes. When the epiFEG genes were cloned together with plasmid pTepi14,
      containing the biosynthetic genes epiABCDQP, the level of epidermin production
      was approximately fivefold higher. The proteins EpiF, -E, and -G are similar in
      deduced sequence and proposed structure to the components of various ABC
      transporter systems. EpiF is a hydrophilic protein with conserved ATP-binding
      sites, while EpiE and -G have six alternating hydrophobic regions and very likely
      constitute the integral membrane domains. When EpiF was overproduced in S.
      carnosus, it was at least partially associated with the cytoplasmic membrane. A
      potential mechanism for how EpiFEG mediates immunity is discussed.

PMID- 8550475
TI  - Porins of Vibrio cholerae: purification and characterization of OmpU.
AB  - Three outer membrane proteins with molecular masses of 40, 38, and 27 kDa of the
      hypertoxinogenic strain 569B of Vibrio cholerae have been purified to
      homogeneity. The synthesis of all the three proteins is regulated by the
      osmolarity of the growth medium. The pore-forming ability of the 40-kDa protein,
      OmpT, and the 38-kDa protein, OmpU, has been demonstrated by using liposomes, in
      which these proteins were embedded. The 27-kDa protein, OmpX, though
      osmoregulated, is not a porin. OmpU constitutes 30% of the total outer membrane
      protein when grown in the presence of 1.0% NaCl in the growth medium and 60% in
      the absence of NaCl. OmpU is an acidic protein and is a homotrimer of 38-kDa
      monomeric units. Its secondary structure contains predominantly a beta-sheet, and
      three to four Ca2+ ions are associated with each monomeric unit. Removal of Ca2+
      irreversibly disrupts the structure and pore-forming ability of the protein. The
      pore size of OmpU is 1.6 nm, and the specific activity of the OmpU channel is two
      to threefold higher than that of Escherichia coli porin OmpF, synthesis of which
      resembles that of OmpU with respect to the osmolarity of the growth medium. The
      pore size of OmpT, which is analogous to OmpC of E. coli, is smaller than that of
      OmpU. Southern blot hybridization of V. cholerae genomic DNA digested with
      several restriction endonucleases with nick-translated E. coli ompF as the probe
      revealed no nucleotide sequence homology between the ompU and ompF genes. OmpU is
      also not antigenically related to OmpF. Anti-OmpF antiserum, however, cross
      reacted with the 45-kDa V. cholerae outer membrane protein, OmpS, the synthesis
      of which is regulated by the presence of maltose in the growth medium. OmpU
      hemagglutinated with rabbit and human blood. This toxR-regulated protein is one
      of the possible virulence determinants in V. cholerae (V. L. Miller and J. J.
      Mekalanos, J. Bacteriol. 170:2575-2583, 1988).

PMID- 8550477
TI  - Ultrastructural organization and regulation of a biomaterial adhesin of
      Staphylococcus epidermidis.
AB  - Coagulase-negative staphylococci have emerged as important pathogens in
      infections associated with intravascular devices. Microbial adherence to
      biomaterial surfaces is a crucial step in the pathogenesis of these infections.
      Staphylococcal surface proteins (herein referred to as SSP-1 and SSP-2) are
      involved in the attachment of Staphylococcus epidermidis 354 to polystyrene. In
      the present study we show that the adhesin protrudes from the cell surface as a
      fimbria-like polymer. Furthermore, in vitro proteolytic cleavage of SSP-1
      produces an SSP-2-like protein which coincides with a loss of adhesive function.
      SSP-1 expression is down-regulated in a phenotypical variant of S. epidermidis
      354 whereas SSP-2 expression is not. These results could suggest that proteolytic
      cleavage is a key to the regulation of the adhesive state of S. epidermidis in
      vivo.

PMID- 8550478
TI  - Salmonella typhimurium fimbrial phase variation and FimA expression.
AB  - Bacteria in a nonfimbriate phase because of continuous aeration of liquid
      cultures produce FimA in amounts similar to those produced by fimbriate bacteria.
      However, relatively low FimA production was observed in nonfimbriate-phase
      cultures obtained by growth on solid media or by anaerobic incubation. Regardless
      of the fimbrial phase of Salmonella typhimurium, the fimA promoter region was
      always oriented in the direction that might allow fimA transcription.

PMID- 8550479
TI  - Exchange of precursor-specific elements between Pro-sigma E and Pro-sigma K of
      Bacillus subtilis.
AB  - sigma E and sigma K are sporulation-specific sigma factors of Bacillus subtilis
      that are synthesized as inactive proproteins. Pro-sigma E and pro-sigma K are
      activated by the removal of 27 and 20 amino acids, respectively, from their amino
      termini. To explore the properties of the precursor-specific sequences, we
      exchanged the coding elements for these domains in the sigma E and sigma K
      structural genes and determined the properties of the resulting chimeric proteins
      in B. subtilis. The pro-sigma E-sigma K chimera accumulated and was cleaved into
      active sigma K, while the pro-sigma K-sigma E fusion protein failed to accumulate
      and is likely unstable in B. subtilis. A fusion of the sigE "pro" sequence to an
      unrelated protein (bovine rhodanese) also formed a protein that was cleaved by
      the pro-sigma E processing apparatus. The data suggest that the sigma E pro
      sequence contains sufficient information for pro-sigma E processing as well as a
      unique quality needed for sigma E accumulation.

PMID- 8550480
TI  - Multiple sigma factor genes in Brevibacterium lactofermentum: characterization of
      sigA and sigB.
AB  - Four rpoD hybridizing signals have been identified in the chromosome of
      Brevibacterium lactofermentum. Two rpoD-like genes, sigA and sigB, have been
      cloned and sequenced, and they encode principal sigma factors of the RNA
      polymerase. The deduced amino acid sequences of SigA and SigB showed very high
      similarities to those of Mycobacterium smegmatis MysA and MysB proteins,
      respectively, and also to those of HrdB proteins from different Streptomyces
      species. SigA and SigB maintain the conserved motifs of sigma 70-like principal
      sigma factors. sigB is closely linked to the dtxR gene (encoding a repressor of
      iron-regulated promoters homologous to the diphtheria toxin repressor from
      Corynebacterium diphtheriae.

PMID- 8550481
TI  - Differentiation of Serratia liquefaciens into swarm cells is controlled by the
      expression of the flhD master operon.
AB  - The velocity with which a swarming colony of Serratia liquefaciens colonizes the
      surface of a suitable solid substratum was controlled by modulating the
      expression of the flhD master operon. In liquid medium, the stimulation of flhD
      expression resulted in filamentous, multinucleate, and hyperflagellated cells
      that were indistinguishable from swarm cells isolated from the edge of a swarm
      colony. Thus, expression of the flhD master operon appears to play a central role
      in the process of swarm cell differentiation.

PMID- 8550482
TI  - A Bacillus subtilis malate dehydrogenase gene.
AB  - A Bacillus subtilis gene for malate dehydrogenase (citH) was found downstream of
      genes for citrate synthase and isocitrate dehydrogenase. Disruption of citH
      caused partial auxotrophy for aspartate and a requirement for aspartate during
      sporulation. In the absence of aspartate, citH mutant cells were blocked at a
      late stage of spore formation.

PMID- 8550483
TI  - The lipooligosaccharides of Haemophilus ducreyi are highly sialylated.
AB  - The major lipooligosaccharides of the sexually transmitted pathogen Haemophilus
      ducreyi 35000 have been previously found to terminate in N-acetyllactosamine and
      sialyl-N-acetyllactosamine, Neu5Ac alpha 2-->3Gal beta 1-->4GlcNAc (W. Melaugh,
      N. J. Phillips, A. A. Campagnari, M. V. Tullius, and B. W. Gibson, Biochemistry
      33: 13070-13078, 1994). In this study, mass spectrometry and composition analyses
      have shown that the lipooligosaccharides from three other H. ducreyi strains also
      contain N-acetyllactosamine and are highly sialylated (approximately 30 to 50%),
      although one African strain was found to contain neither of these structural
      features.

PMID- 8550484
TI  - Isolation of Vibrio harveyi acyl carrier protein and the fabG, acpP, and fabF
      genes involved in fatty acid biosynthesis.
AB  - We report the isolation of Vibrio harveyi acyl carrier protein (ACP) and cloning
      of a 3,973-bp region containing the fabG (encoding 3-ketoacyl-ACP reductase, 25.5
      kDa), acpP (encoding ACP, 8.7 kDa), fabF (encoding 3-ketoacyl-ACP synthase II,
      43.1 kDa), and pabC (encoding aminodeoxychorismate lyase, 29.9 kDa) genes.
      Predicted amino acid sequences were, respectively, 78, 86, 76, and 35% identical
      to those of the corresponding Escherichia coli proteins. Five of the 11 sequence
      differences between V. harveyi and E. coli ACP were nonconservative amino acid
      differences concentrated in a loop region between helices I and II.

PMID- 8550485
TI  - Osmotic regulation of intracellular solute pools in Lactobacillus plantarum.
AB  - Bacteria respond to changes in medium osmolarity by varying the concentrations of
      specific solutes in order to maintain constant turgor pressure. The cytoplasmic
      pools of K+, proline, glutamate, alanine, and glycine of Lactobacillus plantarum
      ATCC 14917 increased when the osmolarity of the growth media was raised from 0.20
      to 1.51 osmol/kg by KCL. When glycine-betaine was present in a high-osmolarity
      chemically defined medium, it was accumulated to a high cytoplasmic
      concentration, while the concentrations of most other osmotically important
      solutes decreased. These observations, together with the effects of glycine
      betaine on the specific growth rate under high-osmolarity conditions, suggest
      that glycine-betaine is preferentially accumulated in L. plantarum. Uptake of
      glycine-betaine, proline, glutamate, and alanine was studied in cells that were
      alternately exposed to hyper- and hypo-osmotic stresses. The rate of uptake of
      proline and glycine-betaine increased instantaneously upon increasing the
      osmolarity, whereas that of other amino acids did not. This activation occurred
      also under conditions in which protein synthesis was inhibited was most
      pronounced when cells were pregrown at high osmolarity. The duration of net
      transport was a function of the osmotic strength of the assay medium. Glutamate
      uptake was not activated by an osmotic upshock, and the uptake of alanine was low
      under all conditions tested. When cells were subjected to osmotic downshock, a
      rapid efflux of accumulated glycine-betaine, proline, and alanine occurred
      whereas the pools of other amin acids remained unaffected. The results indicate
      that osmolyte efflux is, at least to some extent, mediated via specific
      osmotically regulated efflux systems and not via nonspecific mechanisms as has
      been suggested previously.

PMID- 8550486
TI  - Development of techniques for the genetic manipulation of the gliding bacterium
      Cytophaga johnsonae.
AB  - Cytophaga johnsonae displays many features that make it an excellent model of
      bacterial gliding motility. Unfortunately, genetic analyses of C. johnsonae, or
      any related gliding bacteria, were not possible because of a complete lack of
      selectable markers, cloning vectors, transposons, and convenient methods of gene
      transfer. As a first step toward a molecular analysis of gliding motility of C.
      johnsonae, we developed these genetic techniques and tools. Common broad-host
      range plasmids and transposons did not function in C. johnsonae. We identified
      one Bacteroides transposon, Tn4351, that could be introduced into C. johnsonae on
      plasmid R751 by conjugation from Escherichia coli. Tn4351 inserted in the C.
      johnsonae genome and conferred erythromycin resistance. Tn-4351 insertions
      resulted in auxotrophic mutations and motility mutations. We constructed novel
      plasmids and cosmids for genetic analyses of C. johnsonae. These cloning vectors
      are derived from a small cryptic plasmid (pCP1) that we identified in the fish
      pathogen Cytophaga psychrophila D12. These plasmids contain the ermF
      (erythromycin resistance) gene from Tn4351 and a variety of features that
      facilitate propagation and selection in E. coli and conjugative transfer from E.
      coli to C. johnsonae.

PMID- 8550487
TI  - Characterization of uncultivated prokaryotes: isolation and analysis of a 40
      kilobase-pair genome fragment from a planktonic marine archaeon.
AB  - One potential approach for characterizing uncultivated prokaryotes from natural
      assemblages involves genomic analysis of DNA fragments retrieved directly from
      naturally occurring microbial biomass. In this study, we sought to isolate large
      genomic fragments from a widely distributed and relatively abundant but as yet
      uncultivated group of prokaryotes, the planktonic marine Archaea. A fosmid DNA
      library was prepared from a marine picoplankton assemblage collected at a depth
      of 200 m in the eastern North Pacific. We identified a 38.5-kbp recombinant
      fosmid clone which contained an archaeal small subunit ribosomal DNA gene.
      Phylogenetic analyses of the small subunit rRNA sequence demonstrated it close
      relationship to that of previously described planktonic archaea, which form a
      coherent group rooted deeply within the Crenarchaeota branch of the domain
      Archaea. Random shotgun sequencing of subcloned fragments of the archaeal fosmid
      clone revealed several genes which bore highest similarity to archaeal homologs,
      including large subunit ribosomal DNA and translation elongation factor 2 (EF2).
      Analyses of the inferred amino acid sequence of archaeoplankton EF2 supported its
      affiliation with the Crenarchaeote subdivision of Archaea. Two gene fragments
      encoding proteins not previously found in Archaea were also identified: RNA
      helicase, responsible for the ATP-dependent alteration of RNA secondary
      structure, and glutamate semialdehyde aminotransferase, an enzyme involved in
      initial steps of heme biosynthesis. In total, our results indicate that genomic
      analysis of large DNA fragments retrieved from mixed microbial assemblages can
      provide useful perspective on the physiological potential of abundant but as yet
      uncultivated prokaryotes.

PMID- 8550488
TI  - Lactococcin G is a potassium ion-conducting, two-component bacteriocin.
AB  - Lactococcin G is a novel lactococcal bacteriocin whose activity depends on the
      complementary action of two peptides, termed alpha and beta. Peptide synthesis of
      the alpha and beta peptides yielded biologically active lactococcin G, which was
      used in mode-of-action studies on sensitive cells of Lactococcus lactis.
      Approximately equivalent amounts of both peptides were required for optimal
      bactericidal effect. No effect was observed with either the alpha or beta peptide
      in the absence of the complementary peptide. The combination of alpha and beta
      peptides (lactococcin G) dissipates the membrane potential (delta omega), and as
      a consequence cells release alpha-aminoisobutyrate, a non-metabolizable alanine
      analog that is accumulated through a proton motive-force dependent mechanism. In
      addition, the cellular ATP level is dramatically reduced, which results in a
      drastic decrease of the ATP-driven glutamate uptake. Lactococcin G does not form
      a proton-conducting pore, as it has no effect on the transmembrane pH gradient.
      Dissipation of the membrane potential by uncouplers causes a slow release of
      potassium (rubidium) ions. However, rapid release of potassium was observed in
      the presence of lactococcin G. These data suggest that the bactericidal effect of
      lactococcin G is due to the formation of potassium-selective channels by the
      alpha and beta peptides in the target bacterial membrane.

PMID- 8550489
TI  - Proteolytic degradation of dinitrogenase reductase from Anabaena variabilis (ATCC
      29413) as a consequence of ATP depletion and impact of oxygen.
AB  - Both components of nitrogenase, dinitrogenase and dinitrogenase reductase, are
      rapidly inactivated by oxygen. To investigate the proteolytic degradation of
      dinitrogenase reductase irreversibly destroyed by high oxygen concentrations, we
      carried out in vitro experiments with heterocyst extracts from Anabaena
      variabilis ATCC 29413. The results indicate a direct dependence of degradation on
      the applied oxygen concentration. Although the degrees of degradation were
      similar for both the modified and unmodified subunits of dinitrogenase reductase,
      there was a significant difference with respect to the cleavage products
      observed. The pattern of effective protease inhibitors suggests the involvement
      of serine proteases with chymotrypsin- and trypsin-like specificity. A protective
      effect was obtained by saturation of the nucleotide binding sites of
      dinitrogenase reductase with either ATP or ADP. As shown by gel filtration
      experiments, the adenylates prevented the nitrogenase subunits from extensive
      noncovalent aggregation, which is usually considered evidence for a denaturing
      process. The in vitro degradation of dinitrogenase reductase is discussed in
      connection with previous reports on degradation of nitrogenase in cyanobacteria
      under oxygen stress and/or starvation.

PMID- 8550490
TI  - Identification and molecular characterization of a putative regulatory locus that
      affects autolysis in Staphylococcus aureus.
AB  - Previously in our laboratory, a PCR-based strategy was used to isolate potential
      sensor gene fragments from the Staphyloccus aureus genome. One DNA fragment was
      isolated that shared strong sequence similarity to genes encoding bacterial
      sensor proteins, indicating that it originated from within a potential
      staphylococcal sensor protein gene. In this study, the DNA surrounding the PCR
      product origin was cloned and sequenced. This analysis revealed the presence of
      two genes, termed lytS and lytR, whose deduced amino acid sequences were similar
      to those of members of the two-component regulatory system family of proteins. S.
      aureus cells containing an insertional disruption of lytS exhibited a marked
      propensity to form aggregates in liquid culture, suggesting that alterations in
      cell surface components exist in this strain. Transmission electron microscopic
      examination of these cells revealed that the cell surface was rough and diffuse
      and that a large proportion of the cell population had lysed. The lytS mutant
      also exhibited increased autolysis and an altered level of murein hydrolase
      activity produced compared with the parental strain, NCTC 8325-4. These data
      suggest that the lytS and lytR gene products control the rate of autolysis in S.
      aureus by affecting the intrinsic murein hydrolase activity associated with the
      cell.

PMID- 8550491
TI  - Open reading frame 176 in the photosynthesis gene cluster of Rhodobacter
      capsulatus encodes idi, a gene for isopentenyl diphosphate isomerase.
AB  - Isopentenyl diphosphate (IPP) isomerase catalyzes an essential activation step in
      the isoprenoid biosynthetic pathway. A database search based on probes from the
      highly conserved regions in three eukaryotic IPP isomerases revealed substantial
      similarity with ORF176 in the photosynthesis gene cluster in Rhodobacter
      capsulatus. The open reading frame was cloned into an Escherichia coli expression
      vector. The encoded 20-kDa protein, which was purified in two steps by ion
      exchange and hydrophobic interaction chromatography, catalyzed the
      interconversion of IPP and dimethylallyl diphosphate. Thus, the photosynthesis
      gene cluster encodes all of the enzymes required to incorporate IPP into the
      ultimate carotenoid and bacteriochlorophyll metabolites in R. capsulatus. More
      recent searches uncovered additional putative open reading frames for IPP
      isomerase in seed-bearing plants (Oryza sativa, Arabidopsis thaliana, and Clarkia
      breweri), a worm (Caenorhabditis elegans), and another eubacterium (Escherichia
      coli). The R. capsulatus enzyme is the smallest of the IPP isomerases to be
      identified thus far and may consist mostly of a fundamental catalytic core for
      the enzyme.

PMID- 8550492
TI  - Alginate synthesis in Pseudomonas aeruginosa: the role of AlgL (alginate lyase)
      and AlgX.
AB  - Previous studies localized an alginate lyase gene (algL) within the alginate
      biosynthetic gene cluster at 34 min on the Pseudomonas aeruginosa chromosome.
      Insertion of a Tn501 polar transposon in a gene (algX) directly upstream of algL
      in mucoid P. aeruginosa FRD1 inactivated expression of algX, algL, and other
      downstream genes, including algA. This strain is phenotypically nonmucoid;
      however, alginate production could be restored by complementation in trans with a
      plasmid carrying all of the genes inactivated by the insertion, including algL
      and algX. Alginate production was also recovered when a merodiploid that
      generated a complete alginate gene cluster on the chromosome was constructed.
      However, alginate production by merodiploids formed in the algX::Tn501 mutant
      using an alginate cluster with an algL deletion was not restored to wild-type
      levels unless algL was provided on a plasmid in trans. In addition,
      complementation studies of Tn501 mutants using plasmids containing specific
      deletions in either algL or algX revealed that both genes were required to
      restore the mucoid phenotype. Escherichia coli strains which expressed algX
      produced a unique protein of approximately 53 kDa, consistent with the gene
      product predicted from the DNA sequencing data. These studies demonstrate that
      AlgX, whose biochemical function remains to be defined, and AlgL, which has
      alginate lyase activity, are both involved in alginate production by P.
      aeruginosa.

PMID- 8550493
TI  - Radioresistance of Deinococcus radiodurans: functions necessary to survive
      ionizing radiation are also necessary to survive prolonged desiccation.
AB  - Forty-one ionizing radiation-sensitive strains of Deinococcus radiodurans were
      evaluated for their ability to survive 6 weeks of desiccation. All exhibited a
      substantial loss of viability upon rehydration compared with wild-type D.
      radiodurans. Examination of chromosomal DNA from desiccated cultures revealed a
      time-dependent increase in DNA damage, as measured by an increase in DNA double
      strand breaks. The evidence presented suggests that D. radiodurans' ionizing
      radiation resistance is incidental, a consequence of this organism's adaptation
      to a common physiological stress, dehydration.

PMID- 8550494
TI  - Transcription of the glutamyl-tRNA reductase (hemA) gene in Salmonella
      typhimurium and Escherichia coli: role of the hemA P1 promoter and the arcA gene
      product.
AB  - In Salmonella typhimurium and Escherichia coli, the hemA gene encodes the enzyme
      glutamyl-tRNA reductase, which catalyzes the first committed step in the heme
      biosynthetic pathway. It has recently been reported that a lac operon fusion to
      the hemA promoter of E. coli is induced 20-fold after starvation for heme.
      Induction was dependent on the transcriptional regulator ArcA, with a second
      transcriptional regulator, FNR, playing a negative role specifically under
      anaerobic conditions (S. Darie and R. P. Gunsalus, J. Bacteriol. 176:5270-5276,
      1994). We have investigated the generality of this effect by examining the
      response to heme starvation of a number of lac operon fusions to the hemA
      promoters of both E. coli and S. typhimurium. We confirmed that such fusions are
      induced during starvation of a hemA auxotroph, but the level of induction
      observed was maximally sixfold and for S. typhimurium fusions it was only two- to
      fourfold. Sequences required for high-level expression of hemA lie within 129 bp
      upstream of the major (P1) promoter transcriptional start site. Mutants defective
      in the P1 promoter had greatly reduced hemA-lac expression both in the presence
      and in the absence of ALA. Mutations in arcA had no effect on hemA-lac expression
      in E. coli during normal growth, although the increase in expression during
      starvation for ALA was half that seen in an arcA+ strain. Overexpression of the
      arcA gene had no effect on hemA-lac expression. Primer extension analysis showed
      that RNA 5' ends mapping to the hemA P1 and P2 promoters were not expressed at
      significantly higher levels in induced cultures. These results differ from those
      previously reported.

PMID- 8550495
TI  - Organization of Ureaplasma urealyticum urease gene cluster and expression in a
      suppressor strain of Escherichia coli.
AB  - Ureaplasma urealyticum is a pathogenic ureolytic mollicute which colonizes the
      urogenital tracts of humans. A genetic polymorphism between the two biotypes of
      U. urealyticum at the level of the urease genes was found. The urease gene
      cluster from a biotype 1 representative of U. urealyticum (serotype I) was cloned
      and sequenced. Seven genes were found, with ureA, ureB, and ureC encoding the
      structural subunits and ureE, ureF, ureG, and a truncated ureI) gene encoding
      accessory proteins. Urease expression was not obtained when the plasmid
      containing these genes was incorporated into an opal suppressor strain of
      Escherichia coli, although this enzymatic activity was found in the same E. coli
      strain transformed with pC6b, a plasmid with previously cloned urease genes from
      the U. urealyticum T960 strain of biotype 2 (serotype 8). Although there are 12
      TGA triplets encoding tryptophan within urease genes, the level of expression
      obtained was comparable to the levels reported for other bacterial genes
      expressed in E. coli. Nested deletion experiments allowed us to demonstrate that
      ureD is necessary for urease activity whereas another open reading frame located
      downstream is not. The promoter for ureA and possibly other urease genes was
      identified for both serotypes.

PMID- 8550496
TI  - Dominant negative rat DNA polymerase beta mutants interfere with base excision
      repair in Saccharomyces cerevisiae.
AB  - DNA polymerase beta is one of the smallest known eukaryotic DNA polymerases. This
      polymerase has been very well characterized in vitro, but its functional role in
      vivo has yet to be determined. Using a novel competition assay in Escherichia
      coli, we isolated two DNA polymerase beta dominant negative mutants. When we
      overexpressed the dominant negative mutant proteins in Saccharomyces cerevisiae,
      the cells became sensitive to methyl methanesulfonate. Interestingly,
      overexpression of the same polymerase beta mutant proteins did not confer
      sensitivity to UV damage, strongly suggesting that the mutant proteins interfere
      with the process of base excision repair but not nucleotide excision repair in S.
      cerevisiae. Our data implicate a role for polymerase IV, the S. cerevisiae
      polymerase beta homolog, in base excision repair in S. cerevisiae.

PMID- 8550497
TI  - Salmonella enteritidis agfBAC operon encoding thin, aggregative fimbriae.
AB  - Salmonella enteritidis produces thin, aggregative fimbriae, named SEF17, which
      are composed of polymerized AgfA fimbrin proteins. DNA sequence analysis of a 2
      kb region of S. enteritidis DNA revealed three contiguous genes, agfBAC. The 453
      bp agfA gene encodes the AgfA fimbrin, which was predicted to be 74% identical
      and 86% similar in primary sequence to the Escherichia coli curli structural
      protein, CsgA. pHAG, a pUC18 derivative containing a 3.0-kb HindIII fragment
      encoding agfBAC, directed the in vitro expression of the major AgfA fimbrin, with
      an M(r) of 17,000, and a minor AgfB protein, with an M(r) of 16,000, encoded by
      the 453-bp agfB gene. AgfA was not expressed from pDAG, a pUC18 derivative
      containing a 3.1-kb DraI DNA fragment encoding agfA but not agfB. Primer
      extension analysis identified two adjacent transcription start sites located
      immediately upstream of agfB in positions analogous to those of the E. coli
      curlin csgBA operon. No transcription start sites were located immediately
      upstream of agfA or agfC. Northern (RNA) blot analysis confirmed that
      transcription of agfA was initiated from the agfB promoter region. Secondary
      structure analysis of the putative mRNA transcript for agfBAC predicted the
      formation of a stem-loop structure (delta Gzero, -22 kcal/mol [-91 kJ/mol]) in
      the intercistronic region between agfA and agfC, which may be involved in
      stabilization of the agfBA portion of the agfBAC transcript. agfBAC and flanking
      regions had a high degree of sequence similarity with those counterparts of the
      E. coli curlin csgBA region for which sequence data are available. These data are
      demonstrative of the high degree of similarity between S. enteritidis SEF17
      fimbriae and E. coli curli with respect to fimbrin amino acid sequence and
      genetic organization and, therefore, are indicative of a common and relatively
      recent ancestry.

PMID- 8550498
TI  - A regulator of the flagellar regulon of Escherichia coli, flhD, also affects cell
      division.
AB  - The role of an activator of flagellar transcription in Escherichia coli, flhD,
      was investigated in the regulation of cell division. When grown in tryptone
      broth, flhD mutant cells divided exponentially until they reached a cell density
      of 2.5 x 10(9) cells per ml. Wild-type cells and flhC mutant cells divided
      exponentially until they reached a cell density of 4 x 10(7) cells per ml. flhD
      mutant cells divided 5 times more than wild-type cells before they reduced their
      cell division rate and reached a cell density 37 times higher than that of wild
      type or flhC mutant cultures. In stationary phase, the biomasses of all cultures
      were similar; however, flhD mutant cells were significantly smaller. Additional
      tryptone, Casamino Acids, and individual amino acids, added at the beginning of
      growth, allowed wild-type cells to grow to higher cell densities. Serine was
      determined to have the greatest effect. In contrast, the addition of Casamino
      Acids did not exhibit an effect upon flhD mutant cells. flhD mutant cells
      exhibited normal rates of uptake of serine and other amino acids. In both wild
      type and flhD mutant cultures, the concentrations of serine in the media dropped
      from 140 to 20 microM within the first 2 h of growth. Serine concentrations and
      cell division rates were highly correlated. Wild-type cells reduced their cell
      division rate at a medium concentration of 50 microM serine, and the addition of
      serine at this time caused cells to resume a higher rate of division. We conclude
      that the reduction of the cell division rate in wild-type cells is caused by the
      depletion of serine from the medium and that flhD mutant cells seem to be unable
      to sense this depletion.

PMID- 8550499
TI  - Flagellar assembly in Caulobacter crescentus: a basal body P-ring null mutation
      affects stability of the L-ring protein.
AB  - The P- and L-rings are structural components of the flagellar basal body that are
      positioned in the periplasmic space and outer membrane, respectively. In order to
      explore the mechanism of P- and L-ring assembly, we examined the effect of a null
      mutation in the gene encoding the P-ring subunit, FlgI, on the expression,
      stability, and subcellular localization of the L-ring subunit, FlgH, in
      Caulobacter crescentus. Transcription of the L-ring gene and synthesis of the L
      ring protein were both increased in the P-ring null mutant. However, steady-state
      L-ring protein levels were dramatically reduced compared with those of wild type.
      This reduction, which was not observed in flagellar hook mutants, was due to a
      decreased stability of the L-ring protein. The instability of the L-ring protein
      was apparent throughout the cell cycle of the P-ring mutant and contrasted with
      the fairly constant level of L-ring protein during the cell cycle of wild-type
      cells. Low levels of the L-ring protein were detected exclusively in the cell
      envelope of cells lacking the P-ring, suggesting that, in the absence of P-ring
      assembly, L-ring monomers are unable to form multimeric rings and are thus
      subject to proteolysis in the periplasm.

PMID- 8550500
TI  - Mutations affecting mRNA processing and fimbrial biogenesis in the Escherichia
      coli pap operon.
AB  - The Escherichia coli pap genetic determinant includes 11 genes and encodes
      expression of Pap pili on the bacterial surface. An RNase E-dependent mRNA
      processing event in the intercistronic papB-papA region results in the
      accumulation of a papA-gene-specific mRNA in considerable excess of the primary
      papB-papA mRNA transcription product. We have introduced mutations in the
      intercistronic region and studied the effect in vivo of these mutations on the
      processing event, PapA protein expression, and the biogenesis of fimbriae on the
      bacterial surface. Our studies establish that mRNA processing is an important
      event in the mechanism resulting in differential gene expression of the major pap
      operon. The deletion of sequences corresponding to the major cleavage site
      abolished processing, reduced expression of PapA protein, and resulted in "crew
      cut" bacteria with short fimbrial structures on the bacterial surface. Only a
      limited part of the intercistronic region appeared to be required as the
      recognized target for the processing to occur. Upstream sequences to a position
      within 10 nucleotides of the major RNase E-dependent cleavage site could be
      deleted without any detectable effect on papB-papA mRNA processing, PapA protein
      expression, or fimbria formation. Substitution mutations of specific bases at the
      cleavage site by site-directed mutagenesis showed that there were alternative
      positions at which cleavage could be enhanced, and tests with an in vitro
      processing assay showed that such cleavages were also RNase E dependent. Our
      findings are discussed in relation to other fimbrial operons and other known
      targets of the RNase E endoribonuclease.

PMID- 8550501
TI  - Phenotypic characterization of a tungsten-tolerant mutant of Azotobacter
      vinelandii.
AB  - A tungsten-tolerant mutant strain (CA6) of Azotobacter vinelandii first described
      in 1980 (P. E. Bishop, D. M. L. Jarlenski, and D. R. Hetherington, Proc. Natl.
      Acad. Sci. USA 77:7342-7346, 1980) has been further characterized. Results from
      growth experiments suggest that both nitrogenases 1 and 3 are utilized when CA6
      grows in N-free medium containing Na2MoO4. Strain CA6.1.71, which lacks both
      nitrogenases 2 and 3, grew as well as strain CA in N-free medium containing
      Na2MoO4 after an initial lag. This indicates that nitrogenase 1 is fully
      functional in strain CA6. nifH-lacZ and anfH-lacZ transcriptional fusions were
      expressed in CA6 in the presence of Na2MoO4. Thus, in contrast to wild-type
      strain CA, transcription of the anfHDGK gene cluster in strain CA6 is not
      repressed by Mo. Expression of the vnfD-lacZ fusion was the same in both strains
      CA and CA6. In agreement with the results obtained with lac fusions, subunits of
      both nitrogenases 1 and 3 were found in protein extracts of CA6 cells grown in N
      free medium containing Na2MoO4. However, CA6 cells, cultured in the presence of
      Na2WO4, accumulated nitrogenase 3 proteins without detectable amounts of
      nitrogenase 1 proteins. This indicates that expression of Mo-independent
      nitrogenase 3 is the basis for the tungsten tolerance phenotype of strain CA6. A
      measure of Mo accumulation as a function of time showed that accumulation by
      strain CA6 was slower than that for strain CA. When Mo accumulation was studied
      as a function of Na2MoO4 concentration, the two strains accumulated similar
      amounts of Mo in the concentration range of 0 to 1 microM Na2MoO4 during a 2-h
      period. Within the range of 1 to 5 microM Na2MoO4, Mo accumulation by strain CA
      increased linearly with increasing concentration whereas no further increases
      were observed for strain CA6. These results are consistent with the possibility
      that the tungsten tolerance mutation carried by CA6 is in a Mo transport system.

PMID- 8550502
TI  - Mutants of Myxococcus xanthus dsp defective in fibril binding.
AB  - The dsp mutant of Myxococcus xanthus lacks extracellular fibrils and as a result
      is unable to undergo cohesion, group motility, or development (J. W. Arnold and
      L. J. Shimkets, J. Bacteriol. 170:5765-5770, 1983; J. W. Arnold and L. J.
      Shimkets, J. Bacteriol. 170:5771-5777, 1983; R. M. Behmlander and M. Dworkin, J.
      Bacteriol. 173:7810-7821, 1991; L. J. Shimkets, J. Bacteriol. 166:837-841, 1986;
      L. J. Shimkets, J. Bacteriol. 166:842-848, 1986). However, cohesion and
      development can be phenotypically restored by the addition of isolated fibrils
      (R. M. Behmlander, Ph.D. thesis, University of Minnesota, Minneapolis, 1994; B.
      Y. Chang and M. Dworkin, J. Bacteriol. 176:7190-7196, 1994). As part of our
      attempts to examine the interaction of fibrils and cells of M. xanthus, we have
      isolated a series of secondary mutants of M. xanthus dsp in which cohesion,
      unlike that of the parent strain, could not be rescued by the addition of
      isolated fibrils. Cells of M. xanthus dsp were mutagenized either by ethyl
      methanesulfonate or by Tn5 insertions. Mutagenized cultures were enriched by
      selection of those cells that could not be rescued, i.e., that failed to cohere
      in the presence of isolated fibrils. Seven mutants of M. xanthus dsp, designated
      fbd mutants, were isolated from 6,983 colonies; these represent putative fibril
      receptor-minus mutants. The fbd mutants, like the parent dsp mutant, still lacked
      fibrils, but displayed a number of unexpected properties. They regained group
      motility and the ability to aggregate but not the ability to form mature fruiting
      bodies. In addition, they partially regained the ability to form myxospores. The
      fbd mutant was backcrossed into the dsp mutant by Mx4 transduction. Three
      independently isolated transconjugants showed essentially the same properties as
      the fbd mutants--loss of fibril rescue of cohesion, partial restoration of
      myxospore morphogenesis, and restoration of group motility. These results suggest
      that the physical presence of fibrils is not necessary for group motility,
      myxospore formation, or the early aggregative stage of development. We propose,
      however, that the perception of fibril binding is required for normal social
      behavior and development. The dsp fbd mutants (from here on referred to as fbd
      mutants) open the possibility of isolating and characterizing a putative fibril
      receptor gene.

PMID- 8550503
TI  - Sequencing, distribution, and inactivation of the dipeptidase A gene (pepDA) from
      Lactobacillus helveticus CNRZ32.
AB  - Previously, the gene for a general dipeptidase (pepDA) was isolated from a gene
      bank of Lactobacillus helveticus CNRZ32. The pepDA gene consists of a 1,422-bp
      open reading frame which could encode a polypeptide of 53.5 kDa. No significant
      identity was found between the deduced amino acid sequence of the pepDA product
      and the sequence for other polypeptides reported in GenBank. Southern
      hybridization studies with a pepDA probe indicated that the nucleotide sequence
      for pepDA is not well conserved among a variety of lactic acid bacteria. Growth
      studies indicated that a pepDA deletion had no detectable effect on growth rate
      or acid production by L. helveticus CNRZ32 in milk. Furthermore, no difference in
      total cellular dipeptidase activity was detected between the mutant and wild-type
      strains during logarithmic growth in MRS medium.

PMID- 8550504
TI  - Transcriptional regulation of the Bacillus subtilis menp1 promoter.
AB  - The Bacillus subtilis men genes encode biosynthetic enzymes for formation of the
      respiratory chain component menaquinone. The menp1 promoter previously was shown
      to be the primary cis element for menFD gene expression. In the present work, it
      was found that either supplementation with nonfermentable carbon sources or
      reutilization of glycolytic end products increased menp1 activity in the late
      postexponential phase. The effect on menp1 activity by a particular end product
      (such as acetoin or acetate) was prevented by blocking the corresponding pathway
      for end product utilization. Alteration of a TGAAA motif within the promoter
      region resulted in unregulated menp1 activity throughout the culture cycle,
      irrespective of the carbon source added.

PMID- 8550505
TI  - Phosphoribosyl diphosphate synthetase-independent NAD de novo synthesis in
      Escherichia coli: a new phenotype of phosphate regulon mutants.
AB  - Phosphoribosyl diphosphate-lacking (delta prs) mutant strains of Escherichia coli
      require NAD, guanosine, uridine, histidine, and tryptophan for growth. NAD is
      required by phosphoribosyl diphosphate-lacking mutants because of lack of one of
      the substrates for the quinolinate phosphoribosyltransferase reaction, an enzyme
      of the NAD de novo pathway. Several NAD-independent mutants of a host from which
      prs had been deleted were isolated; all of them were shown to have lesions in the
      pstSCAB-phoU operon, in which mutations lead to derepression of the Pho regulon.
      In addition NAD-independent growth was dependent on a functional quinolinate
      phosphoribosyltransferase. The prs suppressor mutations led to the synthesis of a
      new phosphoryl compound that may act as a precursor for a new NAD biosynthetic
      pathway. This compound may be synthesized by the product of an unknown phosphate
      starvation-inducible gene of the Pho regulon because the ability of pst or phoU
      mutations to suppress the NAD requirement requires PhoB, the transcriptional
      activator of the Pho regulon.

PMID- 8550506
TI  - Further stabilization of 3-isopropylmalate dehydrogenase of an extreme
      thermophile, Thermus thermophilus, by a suppressor mutation method.
AB  - We succeeded in further improvement of the stability of 3-isopropylmalate
      dehydrogenase (IPMDH) from an extreme thermophile, Thermus thermophilus, by a
      suppressor mutation method. We previously constructed a chimeric IPMDH consisting
      of portions of thermophile and mesophile enzymes. The chimeric enzyme is less
      thermostable than the thermophile enzyme. The gene encoding the chimeric enzyme
      was subjected to random mutagenesis and integrated into the genome of a leuB
      deficient mutant of T. thermophilus. The transformants were screened at 76
      degrees C in minimum medium, and three independent stabilized mutants were
      obtained. The leuB genes from these three mutants were cloned and analyzed. The
      sequence analyses revealed Ala-172-->Val substitution in all of the mutants. The
      thermal stability of the thermophile IPMDH was improved by introducing the amino
      acid substitution.

PMID- 8550507
TI  - Low-affinity potassium uptake system in the archaeon Methanobacterium
      thermoautotrophicum: overproduction of a 31-kilodalton membrane protein during
      growth on low-potassium medium.
AB  - During growth on low-K+ medium (1 mM K+), Methanobacterium thermoautotrophicum
      accumulated K+ up to concentration gradients
      ([K+]intracellular/[K+]extracellular) of 25,000- to 50,000-fold. At these
      gradients ([K+]extracellular of < 20 microM), growth ceased but could be
      reinitiated by the addition of K+ or Rb+. During K+ starvation, the levels of a
      protein with an apparent molecular weight of 31,000 increased about sixfold. The
      protein was associated with the membrane and could be extracted by detergents.
      Cell suspensions of M. thermoautotrophicum obtained after K+-limited growth
      catalyzed the transport of both K+ and Rb+ with apparent Km and Vmax values of
      0.13 mM and 140 nmol/min/mg, respectively, for K+ and 3.4 mM and 140 nmol/min/mg,
      respectively, for Rb+. Rb+ competitively inhibited K+ uptake with an inhibitor
      constant of about 10 mM. Membranes of K+-starved cells did not exhibit K+
      stimulated ATPase activity. Immunoblotting with antisera against Escherichia coli
      Kdp-ATPase did not reveal any specific cross-reactivity against membrane proteins
      of K+-starved cells. Cells of M. thermoautotrophicum grown at a high potassium
      concentration (50 mM) catalyzed K+ and Rb+ transport at similar apparent Km
      values (0.13 mM for K+ and 3.3 mM for Rb+) but at significantly lower apparent
      Vmax values (about 60 nmol/min/mg for both K+ and Rb+) compared with K+-starved
      cells. From these data, it is concluded that the archaeon M. thermoautotrophicum
      contains a low-affinity K+ uptake system which is overproduced during growth on
      low-K+ medium.

PMID- 8550508
TI  - Repression of the Escherichia coli modABCD (molybdate transport) operon by ModE.
AB  - The modABC gene products constitute the molybdate-specific transport system in
      Escherichia coli. Another operon coding for two proteins which diverges from the
      modABCD operon has been identified. The first gene of this operon codes for a 262
      amino-acid protein, designated ModE (28 kDa), and the second genes codes for a
      490-amino-acid protein. ModF (54 kDa). The role of ModF has not yet been
      determined; however, mutations in modE depressed modABCD transcription even in
      the presence of molybdate, suggesting that ModE is a repressor. ModE, in the
      presence of 1 mM molybdate, repressed the production of plasmid-encoded ModA and
      ModB' proteins in an in vitro transcription-translation system. DNA mobility
      shift experiments confirmed that ModE binds to an oligonucleotide derived from
      the operator region of the modABCD operon. Further experimentation indicated that
      ModE binding to target DNA minimally requires an 8-bp inverted-repeat sequence,
      TAAC GITA. A highly conserved amino acid sequence, TSARNOXXG (amino acids 125 to
      133), was identified in ModE and homologs from Azotobacter vinelandii,
      Haemophilus influenzae, Rhodobacter capsulatus, and Clostridium pasterianum.
      Mutants with mutations in either T or G of this amino acid sequence were isolated
      as "superrepressor" mutants. These mutant proteins repressed modABCD
      transcription even in the absence of molybdate, which implies that this stretch
      of amino acids is essential for the binding of molybdate by the ModE protein.
      These results show that molybdate transport in E. coli is regulated by ModE,
      which acts as a repressor when bound to molybdate.

PMID- 8550509
TI  - Genetic analysis of Rhizobium meliloti bacA-phoA fusion results in identification
      of degP: two loci required for symbiosis are closely linked to degP.
AB  - The function of the Rhizobium meliloti bacA gene, which is a homolog of the
      Escherichia coli sbmA gene, is required for an intermediate step in nodule
      development. A strain carrying the bacA386::TnphoA fusion was mutagenized with N
      methyl-N'-nitro-N-nitrosoguanidine, and three mutants that had higher levels of
      alkaline phosphatase activity were identified. The mutations in these strains
      were recessive and mapped to the same genetic locus. The gene affected by these
      mutations was identified and sequenced and was found to be a homolog of the E.
      coli degP gene, which encodes a periplasmic endopeptidase. Although degP function
      is important for the virulence of certain intracellular pathogens of mammals, it
      is not required for the R. meliloti-alfalfa symbiosis. The genetic analyses
      involving degP were complicated by the presence of a locus immediately upstream
      of depP that was lethal when present in multiple copies in a DegP- background. R.
      meliloti derivatives carrying insertion mutations in this locus displayed an
      N,N,N',N'-tetramethyl-p-phenylenediamine oxidase-negative phenotype, elicited the
      formation of white cylindrical nodules that did not fix nitrogen, and grew slowly
      in rich medium, suggesting that the locus was a cyc gene encoding a protein
      involved in the biosynthesis of a component or components of a respiratory chain.
      The previously identified fix-382::TnphoA, which similarly causes the formation
      of white cylindrical nodules that do not fix nitrogen, was shown to affect a gene
      that is separate from this cyc gene but extremely closely linked to it.

PMID- 8550510
TI  - Salmonella typhimurium cobalamin (vitamin B12) biosynthetic genes: functional
      studies in S. typhimurium and Escherichia coli.
AB  - In order to study the Salmonella typhimurium cobalamin biosynthetic pathway, the
      S. typhimurium cob operon was isolated and cloned into Escherichia coli. This
      approach has given the new host of the cob operon the ability to make cobalamins
      de novo, an ability that had probably been lost by this organism. In total, 20
      genes of the S. typhimurium cob operon have been transferred into E. coli, and
      the resulting recombinant strains have been shown to produce up to 100 times more
      corrin than the parent S. typhimurium strain. These measurements have been
      performed with a quantitative cobalamin microbiological assay which is detailed
      in this work. As with S. typhimurium, cobalamin synthesis is only observed in the
      E. coli cobalamin-producing strains when they are grown under anaerobic
      conditions. Derivatives of the cobalamin-producing E. coli strains were
      constructed in which genes of the cob operon were inactivated. These strains,
      together with S. typhimurium cob mutants, have permitted the determination of the
      genes necessary for cobalamin production and classification of cbiD and cbiG as
      cobl genes. When grown in the absence of endogenous cobalt, the oxidized forms of
      precorrin-2 and precorrin-3, factor II and factor III, respectively, were found
      to accumulate in the cytosol of the corrin-producing E. coli. Together with the
      finding that S. typhimurium cbiL mutants are not complemented with the homologous
      Pseudomonas denitrificans gene, these results lend further credence to the theory
      that cobalt is required at an early stage in the biosynthesis of cobalamins in S.
      typhimurium.

PMID- 8550511
TI  - The permeability of the wall fabric of Escherichia coli and Bacillus subtilis.
AB  - To study the overall structure of the peptidoglycan fabric of the sacculi of gram
      negative and gram-positive walls, actively growing cultures of Escherichia coli
      and Bacillus subtilis were treated with boiling sodium dodecyl sulfate solutions.
      The sacculi were then treated with enzymes to eliminate proteins and nucleic
      acids. These intact saccoli were probed with fluorescein-labeled dextrans with a
      range of known molecular weights. The penetration of the probes could be
      monitored by the negative-staining appearance in the fluorescence microscope. At
      several chosen times, the molecular weight fraction that allowed barely
      observable entry of the fluorescein-labeled probe and the molecular weight
      fraction that penetrated to achieve almost, but not quite, the concentration of
      probe in the solution external to the sacculi were determined. From three pairs
      of times and molecular weights that met one or the other of these two criteria,
      the effective pore size could be calculated. The minimum size of protein molecule
      that could diffuse through the pores was also calculated. Two mathematical
      models, which gave essentially the same results, were used to interpret the
      experimental data: one for the permeation of random coils through a surface
      containing holes and the other for rigid spheres diffusing through water-filled
      cylindrical pores. The mean estimate of the effective hole radius in walls from
      E. coli is 2.06 nm, and that of the effective hole size in walls from B. subtilis
      is 2.12 nm. These results are supported by experiments in which the loss of
      preloaded cells was monitored. Various fluorescein-labeled dextran samples were
      mixed with samples of intact cell walls, held for a long time, and then diluted.
      The efflux of the dextrans was monitored. Neither large nor small dextrans
      stained under these conditions. Only with dextran samples of a sufficiently small
      size were the sacculi filled during the preincubation period, and only with the
      largest of these could the probe not escape quickly. From the pore (or mesh)
      size, it can be concluded that the wall fabric of both organisms has few
      imperfections and that the major passageway is through the smallest possible
      pore, or "tessera," formed by the maximal cross-linking of the peptides from
      glycan chain to glycan chain compatible with the degree of rotational flexibility
      of the chains of repeating disaccharides of N-acetyl muramic acid and N-acetyl
      glucosamine. A tessera is composed of two chains of eight saccharides cross
      linked by two octapeptides. The size of a globular hydrophilic molecule, if it
      did not bind to wall components, that could pass freely through the meshwork of
      an unstretched sacculus of either organism is roughly 25 kDa. We stress that this
      is only a rough estimate, and it may be possible for proteins of less than 50 kDa
      to pass through the native wall during normal growth conditions.

PMID- 8550512
TI  - Molecular analysis of the poly(3-hydroxyalkanoate) synthase gene from a
      methylotrophic bacterium, Paracoccus denitrificans.
AB  - A 3.6-kb EcoRI-SalI fragment of Paracoccus denitrificans DNA hybridized with a
      DNA probe carrying the poly(3-hydroxyalkanoate) (PHA) synthase gene (phaC) of
      Alcaligenes eutrophus. Nucleotide sequence analysis of this region showed the
      presence of a 1,872-bp open reading frame (ORF), which corresponded to a
      polypeptide with a molecular weight of 69,537. Upstream of the ORF, a promoter
      like sequence was found. Escherichia coli carrying the fusion gene between lacZ
      and the ORF accumulated a level of poly(3-hydroxybutyrate) that was as much as 20
      wt% of the cell dry weight in the presence of beta-ketothiolase and
      acetoacetylcoenzyme A reductase genes of A. eutrophus. The ORF was designated
      phaCPd. A plasmid vector carrying the phaCPd'-'lacZ fusion gene downstream of the
      promoter-like sequence expressed beta-galactosidase activity in P. denitrificans.
      When a multicopy and broad-host-range vector carrying the ORF along with the
      promoter-like sequence was introduced into P. denitrificans, the PHA content in
      the cells increased by twofold compared with cells carrying only a vector
      sequence.

PMID- 8550513
TI  - Characterization of 2-ketoisovalerate ferredoxin oxidoreductase, a new and
      reversible coenzyme A-dependent enzyme involved in peptide fermentation by
      hyperthermophilic archaea.
AB  - Cell extracts of the proteolytic and hyperthermophilic archaea Thermococcus
      litoralis, Thermococcus sp. strain ES-1, Pyrococcus furiosus, and Pyrococcus sp.
      strain ES-4 contain an enzyme which catalyzes the coenzyme A-dependent oxidation
      of branched-chain 2-ketoacids coupled to the reduction of viologen dyes or
      ferredoxin. This enzyme, termed VOR (for keto-valine-ferredoxin oxidoreductase),
      has been purified from all four organisms. All four VORs comprise four different
      subunits and show amino-terminal sequence homology. T. litoralis VOR has an M(r)
      of ca. 230,000, with subunit M(r) values of 47,000 (alpha), 34,000 (beta), 23,000
      (gamma), and 13,000 (delta). It contains about 11 iron and 12 acid-labile sulfide
      atoms and 13 cysteine residues per heterotetramer (alpha beta gamma delta), but
      thiamine pyrophosphate, which is required for catalytic activity, was lost during
      purification. The most efficient substrates (kcat/Km > 1.0 microM-1 s-1; Km < 100
      microM) for the enzyme were the 2-ketoacid derivatives of valine, leucine,
      isoleucine, and methionine, while pyruvate and aryl pyruvates were very poor
      substrates (kcat/Km < 0.2 microM-1 s-1) and 2-ketoglutarate was not utilized. T.
      litoralis VOR also functioned as a 2-ketoisovalerate synthase at 85 degrees C,
      producing 2-ketoisovalerate and coenzyme A from isobutyryl-coenzyme A (apparent
      Km, 250 microM) and CO2 (apparent Km, 48 mM) with reduced viologen as the
      electron donor. The rate of 2-ketoisovalerate synthesis was about 5% of the rate
      of 2-ketoisovalerate oxidation. The optimum pH for both reactions was 7.0. A
      mechanism for 2-ketoisovalerate oxidation based on data from substrate-induced
      electron paramagnetic resonance spectra is proposed, and the physiological role
      of VOR is discussed.

PMID- 8550514
TI  - Expression from the nifB promoter of Azotobacter vinelandii can be activated by
      NifA, VnfA, or AnfA transcriptional activators.
AB  - In Azotobacter vinelandii, nifB is required for the activity of all three
      nitrogenases. Expression of a nifB-lacZ fusion was examined to determine which
      regulatory gene products are important for nifB expression and how its
      transcription is regulated in response to metals. In all conditions, expression
      in A. vinelandii was eliminated by an rpoN mutation, confirming the absolute
      requirement for sigma N. In the wild type, nifB-lacZ expression was approximately
      twofold higher in cells grown with Mo than without. Expression was negligible in
      a nifA mutant grown with Mo but was much higher in Mo-free medium, suggesting
      that in these conditions, another sigma N-dependent activator was responsible for
      nifB expression, possibly VnfA, AnfA, or NtrC. Although expression of the nifB
      lacZ fusion in A. vinelandii vnfA, anfA, and ntrC mutants was little different
      from that in the wild type, nifB transcription could be activated by NifA, VnfA,
      or a truncated form of AnfA in Escherichia coli. The two potential NifA binding
      sites centered at -87 and -129 bp upstream of the transcription start site each
      overlapped a VnfA recognition sequence, motifs also found in Azotobacter
      chroococcum in two exactly conserved regions. Deletion analysis showed that both
      regions are important for nifB expression. Activation of the full-length promoter
      by AnfA was impaired by overexpressing the DNA-binding domain of NifA, suggesting
      that binding of NifA and AnfA can be competitive.

PMID- 8550515
TI  - Conversion of a linear to a circular plasmid in the relapsing fever agent
      Borrelia hermsii.
AB  - Spirochetes of the genus Borrelia have genomes composed of both linear and
      circular replicons. We characterized the genomic organization of B. burgdorferi,
      B. hermsii, B. turicatae, and B. anserina with pulsed-field gel electrophoresis.
      All four species contained a linear chromosome approximately 1 Mb in size and
      multiple linear plasmids in the 16- to 200-kb size range. Plasmids 180 and 170 kb
      in size, present in the relapsing fever agents B. hermsii and B. turicatae but
      not in the other two species, behaved as linear duplex DNA molecules under
      different electrophoretic conditions. A variant of strain HSI of B. hermsii had a
      180-kb circular instead of linear plasmid. There were no detectable differences
      in the growth rates or in the expression of cellular proteins between cells
      bearing linear forms and those bearing circular forms of the plasmid. The
      conversion to a circular conformation of monomeric length was demonstrated by the
      introduction of strand breaks with irradiation, restriction endonuclease
      analysis, and direct observation of the DNA molecules by fluorescent microscopy.
      Consideration of different models for the replication of linear DNA suggests that
      circular intermediates may be involved in the replication of linear replicons in
      Borrelia spp.

PMID- 8550516
TI  - Role of the C terminus in antigen P1 surface localization in Streptococcus mutans
      and two related cocci.
AB  - The C terminus of the major surface protein P1 from Streptococcus mutans is
      composed of a hydrophilic domain, an LPNTGV motif, a hydrophobic domain, and a
      charged tail. These features are shared by surface proteins from many gram
      positive coccal bacteria. To investigate the role of the C-terminal domains in
      antigen P1 surface localization, full-length and truncated P1 gene constructs,
      which were expressed on the shuttle vector pDL276, were transformed into the P1
      negative mutant S. mutans SM3352, Streptococcus gordonii DL-1, and Enterococcus
      faecalis UV202. Transformants were tested for expression of P1 by enzyme-linked
      immunosorbent assaying and Western blotting. The results showed that full-length
      P1 was expressed by transformants of all three bacteria and was localized on the
      cell surface. A fusion protein composed of the Staphylococcus aureus fibronectin
      binding protein C terminus and the P1 protein N terminus was found to surface
      localize in S. mutans. Deletion of the entire C-terminal domains resulted in P1
      being expressed in the culture supernatant. A P1 truncation, which carried only
      the hydrophilic domain at its C terminus, was found partially associated with the
      cell surface. This truncated P1 was readily removed from the isolated cell wall
      by hot sodium dodecyl sulfate-mercaptoethanol extraction. In contrast, the full
      length P1 remained associated with the isolated cell wall after similar
      treatment, suggesting covalent linkages between the full-length P1 and the cell
      wall. The results described above showed that antigen P1 was anchored to the cell
      wall by its C-terminal domains probably via covalent linkages with the cell wall.
      The results also support a universal mechanism involving the C-terminal domains
      for protein surface localization among this group of gram-positive bacteria.

PMID- 8550517
TI  - Fine tangled pili expressed by Haemophilus ducreyi are a novel class of pili.
AB  - Haemophilus ducreyi synthesizes fine, tangled pili composed predominantly of a
      protein whose apparent molecular weight is 24,000 (24K). A hybridoma, 2D8,
      produced a monoclonal antibody (MAb) that bound to a 24K protein in H. ducreyi
      strains isolated from diverse geographic locations. A lambda gt11 H. ducreyi
      library was screened with MAb 2D8. A 3.5-kb chromosomal insert from one reactive
      plaque was amplified and ligated into the pCRII vector. The recombinant plasmid,
      designated pHD24, expressed a 24K protein in Escherichia coli INV alpha F that
      bound MAb 2D8. The coding sequence of the 24K gene was localized by exonuclease
      III digestion. The insert contained a 570-bp open reading frame, designated ftpA
      (fine, tangled pili). Translation of ftpA predicted a polypeptide with a
      molecular weight of 21.1K. The predicted N-terminal amino acid sequence of the
      polypeptide encoded by ftpA was identical to the N-terminal amino acid sequence
      of purified pilin and lacked a cleavable signal sequence. Primer extension
      analysis of ftpA confirmed the lack of a leader peptide. The predicted amino acid
      sequence lacked homology to known pilin sequences but shared homology with the
      sequences of E. coli Dps and Treponema pallidum antigen TpF1 or 4D, proteins
      which associate to form ordered rings. An isogenic pilin mutant, H. ducreyi
      35000ftpA::mTn3(Cm), was constructed by shuttle mutagenesis and did not contain
      pili when examined by electron microscopy. We conclude that H. ducreyi
      synthesizes fine, tangled pili that are composed of a unique major subunit, which
      may be exported by a signal sequence independent mechanism.

PMID- 8550518
TI  - Synthesis of immediate upshift (Iup) proteins during recovery of marine Vibrio
      sp. strain S14 subjected to long-term carbon starvation.
AB  - Proteins induced during the initial phase of recovery after long-term carbon
      starvation in the marine Vibrio sp. strain S14 were identified by two-dimensional
      gel electrophoresis analysis. Nutritional upshift experiments with pulse-labeled
      cells were performed after addition of glucose to cells starved for 48 h.
      Eighteen proteins synthesized during the first 3 min after substrate addition
      were identified and designated immediate upshift proteins (Iup proteins). They
      were induced at least 10-fold compared with the rate of synthesis during
      starvation. Of the Iup proteins, five are not found in exponentially growing
      cells. Subsequent to the first 3 min of glucose addition, a complex pattern of
      sequential synthesis of proteins made during a transient phase as well as
      proteins made during 60 min of the outgrowth response was monitored. To resolve
      whether the Iup proteins were synthesized from stable transcripts, the initiation
      of transcription was inhibited by rifampin (Rif). Addition of Rif 5 min prior to
      glucose promoted upshift resulted in the synthesis of 12 Iup proteins.
      Furthermore, three Iup proteins were still induced by cells that were Rif treated
      20 min prior to the upshift. These results suggest that stable but silent
      transcripts exist during starvation and that the translation of these mRNA
      species is initiated by substrate addition. This regulatory mechanism may be
      essential for an immediate initiation of the recovery program by the nongrowing
      cell.

PMID- 8550519
TI  - A Bacteroides thetaiotaomicron outer membrane protein that is essential for
      utilization of maltooligosaccharides and starch.
AB  - Previous studies suggested that the first step in utilization of starch by
      Bacteroides thetaiotaomicron was binding of the polysaccharide to the cell
      surface, followed by translocation of the polysaccharide across the outer
      membrane into the periplasm. In this study, we report the molecular
      characterization of a gene that encodes an outer membrane protein that is
      essential for utilization of both maltooligosaccharides and starch. The gene,
      susC, encoded a protein of 115.3 kDa. Antibodies were raised against SusC, and
      the outer membrane location of SusC could be confirmed by Western blot
      (immunoblot) analysis. SusC had a possible signal sequence of between 20 and 39
      amino acids, depending on which N-terminal methionine initiates the start of the
      protein. It also had some features typical of well-characterized outer membrane
      proteins from members of the family Enterobacteriaceae, such as a terminal
      phenylalanine residue and a region in the amino portion of the protein thought to
      be involved in stabilizing the protein in the outer membrane. The amino acid
      sequence, together with results of gene disruption experiments, suggested that
      SusC was not an amylolytic enzyme. Transcriptional fusion experiments, using beta
      glucuronidase as a reporter group, showed that expression of susC was maltose
      regulated at the transcriptional level. This is the first molecular
      characterization of a B. thetaiotaomicron outer membrane protein involved in
      maltooligosaccharide and starch utilization.

PMID- 8550520
TI  - Dual function of PilS during transcriptional activation of the Pseudomonas
      aeruginosa pilin subunit gene.
AB  - The polar pili of Pseudomonas aeruginosa are composed of subunits encoded by the
      pilA gene. Expression of pilA requires the alternative sigma factor RpoN and a
      pair of regulatory elements, PilS and PilR. These two proteins are members of the
      two-component regulatory family, in which PilS is the sensory component and PilR
      is the response regulator. By using expression and localization analyses, in this
      work we show that PilS is synthesized as a 59-kDa polypeptide located in the P.
      aeruginosa cytoplasmic membrane. When the pilS gene is expressed in Escherichia
      coli, aberrant translational initiation results in a smaller, 40-kDa polypeptide.
      Unexpectedly, overexpression of pilS in P. aeruginosa results in decreased
      transcription of the pilA gene. Moreover, fully functional PilS was not required
      for this inhibitory effect. A mutation in the histidine residue essential for
      kinase activity resulted in a protein unable to activate transcription, yet when
      overexpressed in the presence of the wild-type PilS protein, this protein still
      repressed pilin synthesis. A shorter form of PilS, lacking its transmembrane
      segments, was active and fully capable of stimulating pilA transcription but when
      overexpressed did not show the inhibitory effect on pilin expression seen with
      full-length PilS. We also show that overexpression of pilR can activate
      transcription of pilA even in the absence of PilS. On the basis of our studies,
      we propose a complex mechanism of regulation of PilS function, involving other
      cellular factors that control PilS and its activities during the phosphorelay
      mechanism of signal transduction.

PMID- 8550521
TI  - Genetic and topological analyses of the bop promoter of Halobacterium halobium:
      stimulation by DNA supercoiling and non-B-DNA structure.
AB  - The bop gene of wild-type Halobacterium halobium NRC-1 is transcriptionally
      induced more than 20-fold under microaerobic conditions. bop transcription is
      inhibited by novobiocin, a DNA gyrase inhibitor, at concentrations subinhibitory
      for growth. The exposure of NRC-1 cultures to novobiocin concentrations
      inhibiting bop transcription was found to partially relax plasmid DNA
      supercoiling, indicating the requirement of high DNA supercoiling for bop
      transcription. Next, the bop promoter region was cloned on an H. halobium plasmid
      vector and introduced into NRC-1 and S9, a bop overproducer strain. The cloned
      promoter was active in both H. halobium strains, but at a higher level in the
      overproducer than in the wild type. Transcription from the bop promoter on the
      plasmid was found to be inhibited by novobiocin to a similar extent as was
      transcription from the chromosome. When the cloned promoter was introduced into
      S9 mutant strains with insertions in either of two putative regulatory genes, brp
      and bat, no transcription was detectable, indicating that these genes serve to
      activate transcription from the bop promoter in trans. Deletion analysis of the
      cloned bop promoter from a site approximately 480 bp upstream of bop showed that
      a 53-bp region 5' to the transcription start site is sufficient for
      transcription, but a 28-bp region is not. An 11-bp alternating purine-pyrimidine
      sequence within the functional promoter region, centered 23 bp 5' to the
      transcription start point, was found to display DNA supercoiling-dependent
      sensitivity to S1 nuclease and OsO4, which is consistent with a non-B-DNA
      conformation similar to that of left-handed Z-DNA and suggests the involvement of
      unusual DNA structure in supercoiling-stimulated bop gene transcription.

PMID- 8550522
TI  - Role of adenine deaminase in purine salvage and nitrogen metabolism and
      characterization of the ade gene in Bacillus subtilis.
AB  - The isolation of mutants defective in adenine metabolism in Bacillus subtilis has
      provided a tool that has made it possible to investigate the role of adenine
      deaminase in adenine metabolism in growing cells. Adenine deaminase is the only
      enzyme that can deaminate adenine compounds in B. subtilis, a reaction which is
      important for adenine utilization as a purine and also as a nitrogen source. The
      uptake of adenine is strictly coupled to its further metabolism. Salvaging of
      adenine is inhibited by the stringent response to amino acid starvation, while
      the deamination of adenine is not. The level of adenine deaminase was reduced
      when exogenous guanosine served as the purine source and when glutamine served as
      the nitrogen source. The enzyme level was essentially the same whether ammonia or
      purines served as the nitrogen source. Reduced levels were seen on poor carbon
      sources. The ade gene was cloned, and the nucleotide sequence and mRNA analyses
      revealed a single-gene operon encoding a 65-kDa protein. By transductional
      crosses, we have located the ade gene to 130 degrees on the chromosomal map.

PMID- 8550523
TI  - Duplicate isochorismate synthase genes of Bacillus subtilis: regulation and
      involvement in the biosyntheses of menaquinone and 2,3-dihydroxybenzoate.
AB  - Bacillus subtilis has duplicate isochorismate synthase genes, menF and dhbC.
      Isochorismate synthase is involved in the biosynthesis of both the respiratory
      chain component menaquinone (MK) and the siderophore 2,3-dihydroxybenzoate (DHB).
      Several menF and dhbC deletion mutants were constructed to identify the
      contribution made by each gene product to MK and DHB biosynthesis. menF deletion
      mutants were able to produce wild-type levels of MK and DHB, suggesting that the
      dhbC gene product is able to compensate for the lack of MenF. However, a dhbC
      deletion mutant produced wild-type levels of MK but was DHB deficient, indicating
      that MenF is unable to compensate for the lack of DhbC. A menF dhbC double
      deletion mutant was both MK and DHB deficient. Transcription analysis showed that
      expression of dhbC, but not of menF, is regulated by iron concentration. A
      dhbA'::lacZ fusion strain was constructed to examine the effects of mutations to
      the iron box sequence within the dhb promoter region. These mutations abolished
      the iron-regulated transcription of the dhb genes, suggesting that a Fur-like
      repressor protein exists in B. subtilis.

PMID- 8550524
TI  - Spiroplasma citri virus SpV1-derived cloning vector: deletion formation by
      illegitimate and homologous recombination in a spiroplasmal host strain which
      probably lacks a functional recA gene.
AB  - We have previously described the use of the replicative form (RF) of Spiroplasma
      citri virus SpV1 as a vector for expressing an epitope of the P1 adhesin protein
      from Mycoplasma pneumoniae in S. citri (A. Marais, J. M. Bove, S.F. Dallo, J. B.
      Baseman, and J. Renaudin, J. Bacteriol. 175:2783-2787, 1993). We have now studied
      the structural instability of the recombinant RF leading to loss of the DNA
      insert. Analyses of viral clones with deletions have shown that both illegitimate
      and homologous recombination were involved in deletion formation. For one such
      clone, deletion has occurred via a double crossing-over exchange between the
      circular free viral RF and SpV1 viral sequences present in the S. citri host
      chromosome. The homologous recombination process usually requires the RecA
      protein. However, characterization of the recA gene of the S. citri R8A2 host
      strain revealed that over two-thirds of the open reading frame of the recA gene
      was deleted from the C-terminal part, indicating that this particular strain is
      probably RecA deficient.

PMID- 8550525
TI  - Molecular analysis of the anaerobic succinate degradation pathway in Clostridium
      kluyveri.
AB  - A region of genomic DNA from Clostridium kluyveri was cloned in Escherichia coli
      by a screening strategy which was based on heterologous expression of the
      clostridial 4-hydroxybutyrate dehydrogenase gene. The gene region (6,575 bp)
      contained several open reading frames which encoded the coenzyme A (CoA)- and
      NADP+-dependent succinate-semialdehyde dehydrogenase (sucD), the 4
      hydroxybutyrate dehydrogenase (4hbD), and a succinyl-CoA;CoA transferase (cat1),
      as analyzed by heterologous expression in E. coli. An open reading frame encoding
      a putative membrane protein (orfY) and the 5' region of a gene encoding a sigma
      54-homologous sigma factor (sigL) were identified as well. Transcription was
      investigated by Northern (RNA) blot analysis. Protein sequence comparisons of
      SucD and 4HbD revealed similarities to the adhE (aad) gene products from E. coli
      and Clostridium acetobutylicum and to enzymes of the novel class (III) of alcohol
      dehydrogenases. A comparison of CoA-dependent aldehyde dehydrogenases is
      presented.

PMID- 8550526
TI  - Induction of the gap-pgk operon encoding glyceraldehyde-3-phosphate dehydrogenase
      and 3-phosphoglycerate kinase of Xanthobacter flavus requires the LysR-type
      transcriptional activator CbbR.
AB  - In a previous study, a gene (pgk) encoding phosphoglycerate kinase was isolated
      from a genomic library of Xanthobacter flavus. Although this gene is essential
      for autotrophic growth, it is not located within the cbb operon encoding other
      Calvin cycle enzymes. An analysis of the nucleotide sequence upstream from pgk
      showed the presence of a gene encoding glyceraldehyde-3-phosphate dehydrogenase
      and the 3' end of an open reading frame encoding a protein which is 50% identical
      to transketolase encoded by cbbT of X. flavus. Gene fusions between pgk and lacZ
      demonstrated that the gap and pgk genes are organized in an operon. Induction of
      the Calvin cycle in heterotrophically growing cells resulted in a sixfold
      increase in phosphoglycerate kinase activity in parallel with the appearance of
      ribulosebisphosphate carboxylase activity. This superinduction of
      phosphoglycerate kinase did not occur in an X. flavus strain in which cbbR,
      encoding the transcriptional activator of the cbb operon, was disrupted. The
      failure to superinduce the gap-pgk operon is not caused by the absence of a
      functional Calvin cycle, since the expression of this operon in an X. flavus
      strain with a defective ribulosebisphosphate carboxylase enzyme was the same as
      the expression in the wild type. It is therefore concluded that the expression of
      both the cbb and gap-pgk operons is controlled by CbbR.

PMID- 8550527
TI  - Primary structure and phylogeny of the Calvin cycle enzymes transketolase and
      fructosebisphosphate aldolase of Xanthobacter flavus.
AB  - Xanthobacter flavus, a gram-negative facultatively autotrophic bacterium, employs
      the Calvin cycle for the fixation of carbon dioxide. Cells grown under
      autotrophic growth conditions possess an Fe(2+)-dependent fructosebisphosphate
      (FBP) aldolase (class II) in addition to a class I FBP aldolase. By nucleotide
      sequencing and heterologous expression in Escherichia coli, genes encoding
      transketolase (EC 2.2.1.1.; CbbT) and class II FBP aldolase (EC 4.1.2.13; CbbA)
      were identified. A partial open reading frame encoding a protein similar to
      pentose-5-phosphate 3-epimerase was identified downstream from cbbA. A
      phylogenetic tree of transketolase proteins displays a conventional branching
      order. However, the class II FBP aldolase protein from X. flavus is only
      distantly related to that of E. coli. The autotrophic FBP aldolase proteins from
      X. flavus, Alcaligenes eutrophus, and Rhodobacter sphaeroides form a tight
      cluster, with the proteins from gram-positive bacteria as the closest relatives.

PMID- 8550528
TI  - Gene integration in the Escherichia coli chromosome mediated by Tn21 integrase
      (Int21).
AB  - A replication-thermosensitive, pSC101-derived plasmid containing the int gene and
      RHS-2 from the integron in Tn21 and a kanamycin resistance marker has been
      constructed and used to obtain Tn21 integrase (Int21)-mediated plasmid
      integration in the Escherichia coli chromosome. Colonies carrying an integrated
      plasmid were obtained after growth at 42 degrees C. Southern hybridization and
      PCR experiments indicated that they contained the plasmid specifically integrated
      through the RHS into different positions in the E. coli chromosome. Nucleotide
      sequence determination of the plasmid-chromosome junctions showed that
      integration sites in the chromosome were pentanucleotides with the sequence
      described for Int21 secondary sites.

PMID- 8550529
TI  - Negative regulation by fliD, fliS, and fliT of the export of the flagellum
      specific anti-sigma factor, FlgM, in Salmonella typhimurium.
AB  - The fliD operon of Salmonella typhimurium consists of three flagellar genes,
      fliD, fliS, and fliT, and is transcribed in this order. It has been shown that an
      fliD::Tn10 mutation causes an excess export of the flagellum-specific anti-sigma
      factor, FlgM, resulting in an overexpression of flagellar class 3 operons. In
      this study, using gene-disruption mutants in the individual genes in the fliD
      operon, we showed that mutations in any one of the genes in the operon enhanced
      both FlgM export and the expression of flagellar regulon. This indicates that all
      three genes in the operon are involved in the negative regulation of FlgM export.

PMID- 8550530
TI  - Isolation and characterization of flagella and flagellin proteins from the
      Thermoacidophilic archaea Thermoplasma volcanium and Sulfolobus shibatae.
AB  - Isolated flagellar filaments of Sulfolobus shibatae were 15 nm in diameter, and
      they were composed of two major flagellins which have M(r)s of 31,000 and 33,000
      and which stained positively for glycoprotein. The flagellar filaments of
      Thermoplasma volcanium were 12 nm in diameter and were composed of one major
      flagellin which has an M(r) of 41,000 and which also stained positively for
      glycoprotein. N-terminal amino acid sequencing indicated that 18 of the N
      terminal 20 amino acid positions of the 41-kDa flagellin of T. volcanium were
      identical to those of the Methanococcus voltae 31-kDa flagellin. Both flagellins
      of S. shibatae had identical amino acid sequences for at least 23 of the N
      terminal positions. This sequence was least similar to any of the available
      archaeal flagellin sequences, consistent with the phylogenetic distance of S.
      shibatae from the other archaea studied.

PMID- 8550531
TI  - Overexpression, purification, and characterization of UDP-N-acetylmuramyl:L
      alanine ligase from Escherichia coli.
AB  - UDP-N-acetylmuramyl:L-alanine ligase from Escherichia coli was overexpressed more
      than 600-fold and purified to near homogeneity. The purified enzyme was found to
      ligate L-alanine, L-serine, and glycine, as well as the nonnatural amino acid
      beta-chloro-L-alanine, to UDP-N-acetylmuramic acid. On the basis of (i) the
      specificity constants of the enzyme determined for L-alanine, L-serine, and
      glycine and (ii) the levels of these amino acids in the intracellular pool, it
      was calculated that the rates of incorporation of L-serine and glycine into
      peptidoglycan precursor metabolites could maximally amount to 0.1 and 0.5%,
      respectively, of the rate of L-alanine incorporation.

PMID- 8550532
TI  - Soft metal thiol chemistry is not involved in the transport of arsenite by the
      Ars pump.
AB  - The single cysteine in the ArsB protein subunit of the arsenite resistance pump
      was changed to serine and alanine residues. Resistance in cells expressing the
      two mutant arsB genes was the same as in the wild type, and the serine
      substitution had no effect on the arsenite transport properties. These results
      eliminate possible thiol chemistry in translocation. Thus, the pump uses soft
      metal chemistry for metalloactivation and nonmetal chemistry for oxyanion
      transport.

PMID- 8550533
TI  - dTMP biosynthesis in Archaea.
AB  - The biosynthesis of dTMP has been studied in cell extracts of two different
      members of the domain Archaea, Methanosarcina thermophila and Sulfolobus
      solfataricus. In M. thermophila, the dTMP was formed from dUMP and [methylene
      2H2]-5,10-methylenetetrahydrosarcinapterin generated in situ from added
      [methylene-2H2] formaldehyde and the tetrahydrosarcinapterin present in the cell
      extract. In S. solfataricus, the 5,10-methyl-enetetrahydro derivative of a
      synthetic fragment of sulfopterin, the modified folate present in these cells,
      served as the C1 donor. These data indicate that the Archaea thymidylate
      synthases carry out the same basic reaction which occurs in other organisms but
      use the 5,10-methylenetetrahydro derivatives of modified folates as C1 donors.

PMID- 8550535
TI  - Transcription of the Anabaena sp. strain PCC 7120 ntcA gene: multiple transcripts
      and NtcA binding.
AB  - The Anabaena sp. strain PCC 7120 ntcA gene showed multiple transcripts with
      different 5' ends. The relative abundance of transcripts varied in response to
      nitrogen availability. The ntcA product, NtcA, showed binding to the promoter
      region of its own gene. The binding site mapped to a region between the
      transcription start site used under nitrogen-replete conditions and the start
      sites used under nitrogen-limiting conditions, suggesting that NtcA regulates its
      own expression.

PMID- 8550534
TI  - The repetitive element Rep MP 1 of Mycoplasma pneumoniae exists as a core element
      within a larger, variable repetitive mosaic.
AB  - The repetitive element Rep MP 1 has been previously described as a 300-bp element
      present within the chromosome of Mycoplasma pneumoniae in at least 10 copies.
      Sequence found flanking Rep MP 1 in lambda clone 5B52 has been demonstrated to
      exist in multiple copies within the genome of M. pneumoniae. A HindIII M.
      pneumoniae fragment containing the lambda MP 5B52 insert and its flanking
      sequences was cloned into pBluescript. Sequence comparisons of this clone,
      designated pMPH 624-20, with nucleotide database entries showed that in addition
      to the 300-bp Rep MP 1 element, flanking sequence blocks were conserved within
      several other cloned sequences. These short repeated sequences, approximately 80,
      56, and 71 nucleotides long, are termed sRep A, sRep B, and sRep C, respectively.
      These sRep regions were used as probes in the selection of cloned sequences
      containing these repetitive flanking regions. Comparison of these sequences
      demonstrated that the 300-bp Rep MP 1 elements is actually the core element
      within a larger, variable repetitive mosaic. The repetitive regions surrounding
      the core element are found in various combinations, arrangements, and distances
      from the core in a mosaic pattern. These newly identified portions of the mosaic
      do not exist independently of the core element. The core appears to be the only
      invariant portion of this repetitive mosaic.

PMID- 8550536
TI  - Effects of overproducing the universal stress protein, UspA, in Escherichia coli
      K-12.
AB  - A plasmid with the structural uspA gene under the control of a tac promoter was
      used to study the effects of altering uspA expression levels under various growth
      conditions. We found that increasing UspA synthesis to levels corresponding to
      physiologically induced levels decreased the cell growth rate in minimal medium
      and reduced or abolished the cells' capacity to adapt to upshift conditions. As
      was demonstrated by two-dimensional gel electrophoresis, increased uspA
      expression caused global changes in the pattern of protein synthesis. In
      addition, electrophoretic analysis together with V8 protease peptide mapping
      demonstrated that the pIs of some specific proteins became more acidic as a
      result of the elevation of the levels of UspA.

PMID- 8550537
TI  - Efficient insertional mutagenesis in lactococci and other gram-positive bacteria.
AB  - In lactococci, the study of chromosomal genes and their regulation is limited by
      the lack of an efficient transposon mutagenesis system. We associated the
      insertion sequence ISS1 with the thermosensitive replicon pG+ host to generate a
      mutagenic tool that can be used even in poorly transformable strains. ISS1
      transposition is random in different lactococcal strains as well as in
      Enterococcus faecalis and Streptococcus thermophilus. High-frequency random
      insertion (of about 1%) obtained with this system in Lactococcus lactis allows
      efficient mutagenesis, with typically one insertion per cell. After ISS1
      replicative transposition, the chromosome contains duplicated ISS1 sequences
      flanking pG+ host. This structure allows cloning of the interrupted gene. In
      addition, efficient excision of the plasmid leaves a single ISS1 copy at the
      mutated site, thus generating a stable mutant strain with no foreign markers.
      Mutants obtained by this transposition system are food grade and can thus be used
      in fermentation processes.

PMID- 8550538
TI  - Modification of the fatty acid composition of Escherichia coli by coexpression of
      a plant acyl-acyl carrier protein desaturase and ferredoxin.
AB  - Expression of a plant delta 6-palmitoyl (16:0)-acyl carrier protein desaturase in
      Escherichia coli resulted in the accumulation of the novel monounsaturated fatty
      acids delta 6-hexadecenoic acid (16:1 delta 6) and delta 8-octadecenoic acid.
      Amounts of 16:1 delta 6 accumulated by E. coli were increased more than twofold
      by the expression of a plant ferredoxin together with the delta 6-16:0-acyl
      carrier protein desaturase.

PMID- 8550539
TI  - Isolation and characterization of a mutation that alters the substrate
      specificity of the Escherichia coli glucose permease.
AB  - We isolated 10 mannitol-positive mutants from a mannitol-negative Escherichia
      coli strain. These mutations mapped within ptsG, encoding the glucose permease
      (EIIGlc), and resulted in a G-320-to-V substitution that allows EIIGlc to
      transport mannitol. Gly-320 lies within a putative transmembrane helix of EIIGlc
      that may be involved in substrate recognition.

PMID- 8550540
TI  - Painting anatomy on anatomy.
AB  - Painting anatomical features on a model's skin to delineate internal structures
      is a medical illustration technique that rarely has been used. Yet it seems to
      have potential where the scientific point involves muscles, tendons, nerves,
      blood vessels, bones and other tissues that either produce an external
      configuration on the body surface or lie directly underneath. These structures
      can be given clarity and vividness with various paints and pigments that are
      appropriate and safe for applying to human skin.

PMID- 8550541
TI  - Deciding among interactive multimedia technologies.
AB  - The history of multimedia technology is reviewed briefly as are some current
      health science applications. Multimedia hardware and software are discussed. Cost
      and benefits of current interactive multimedia technologies are assessed and key
      factors affecting their successful application are identified and described.

PMID- 8550542
TI  - Reaching higher ground.

PMID- 8550543
TI  - Interaction of bacterial luciferase with 8-substituted flavin mononucleotide
      derivatives.
AB  - Bacterial luciferase catalyzes the emission of visible light from the reaction of
      reduced flavin, molecular oxygen, and an n-alkyl aldehyde. The mechanism of the
      reaction was probed by measuring the electronic effects of various substituents
      at the 8-position of the flavin ring system. Substituent effects were obtained
      for CH3-, Cl-, CH3O-, CH3S-, F-, and H- on the rate of formation and decay of the
      hydroperoxyflavin intermediate and the time courses for the emission of visible
      light. The rate constant for the decay of light emission increases for the series
      Cl < F < H < CH3S < CH3 < CH3O. These results are not compatible with a standard
      Baeyer-Villiger type mechanism for the chemical transformation, but they are
      consistent with a decrease in the electron density at the reaction center of the
      flavin moiety during the rate-limiting step of the reaction.

PMID- 8550544
TI  - Induced release of cell surface protein kinase yields CK1- and CK2-like enzymes
      in tandem.
AB  - Several types of cell exhibit cell surface protein kinase (ecto-PK) activities
      with Ser/Thr-specificity. Ecto-PK sharing certain characteristics of protein
      kinase CK2 can be detached from intact cells by interaction with exogenous
      substrates (Kubler, D., Pyerin, W., Burow, E., and Kinzel, V. (1983) Proc. Natl.
      Acad. Sci. U.S.A. 80, 4021-4025). However, a detailed molecular analysis of this
      ecto-PK was hampered by the vanishingly small amounts of labile enzyme protein
      obtained by substrate-inducible enzyme release. We now describe the stabilization
      and enrichment of released ecto-PK by precipitation with polyethylene glycol
      followed by affinity chromatography on heparin-agarose. Ecto-PK is shown to
      consist of two separate forms released in tandem, ecto-PK I and ecto-PK II.
      Comparison with cell homogenates as well as cell surface biotinylation
      experiments excluded contamination with intracellular PK. Purified ecto-PK I and
      ecto-PK II exhibit respectively selective phosphorylation of CK1- and CK2
      specific peptide substrates, a complementary sensitivity to inhibitory agents and
      a differential use of the cosubstrates ATP and GTP. Ecto-PK I consists of a 40
      kDa moiety; the ecto-PK II is an ensemble of three components of 43- and 40-kDa
      (catalytic subunits) and a noncatalytic 28-kDa subunit. In addition, components
      of the ecto-PK II react with CK2-specific antibodies. Further, comparative
      peptide mapping and the results of mass spectrometry in combination with
      assignment of amino acid sequences confirmed that ecto-PK II is closely related
      if not identical to the protein kinase CK2. Assays with intact cells that result
      in the phosphorylation of a variety of endogenous membrane proteins showed that
      both ecto-PKs participate, and further, certain ecto-PK substrates become
      preferentially labeled by one or another of the enzymes, whereas others are
      phosphorylated by both ecto-PK activities.

PMID- 8550545
TI  - Characterization of a CO-responsive transcriptional activator from Rhodospirillum
      rubrum.
AB  - In Rhodospirillum rubrum, CO induces the expression of at least two transcripts
      that encode an enzyme system for CO oxidation. This regulon is positively
      regulated by CooA, which is a member of the cAMP receptor protein family of
      transcriptional regulators. The transcriptional start site of one of the
      transcripts (cooFSCTJ) has been identified by primer extension. The ability of
      CooA to bind to this promoter in vitro was characterized with DNase I
      footprinting experiments using extracts of a CooA-overproducing strain. CooA- and
      CO-dependent protection was observed for a region with 2-fold symmetry (5'-TGTCA
      N6-CGACA) that is highly similar to the consensus core motifs recognized by cAMP
      receptor protein/FNR family. In vivo analysis in a heterologous background
      indicates that CooA is sufficient for CO-dependent expression, implicating it as
      the likely CO sensor.

PMID- 8550546
TI  - Transcription of the interleukin-1 receptor-related T1 gene is initiated at
      different promoters in mast cells and fibroblasts.
AB  - The delayed early serum response gene T1 encodes glycoproteins of the
      immunoglobulin superfamily with significant sequence similarity to the type 1
      interleukin-1 receptor. The T1 gene is transcribed in fibroblasts into an
      abundant 2.7-kilobase (kb) and a rare 5-kb mRNA in response to proliferation
      inducing stimuli. It gives predominantly rise to the longer transcript in the
      bone marrow of adult mice and in cultured mast cells. Alternative 3' processing
      is responsible for the two mRNA forms. The short transcript encodes a secreted
      protein with marked similarity to the extracellular domain of the interleukin-1
      receptor, whereas the long mRNA is translated into a protein with an additional
      putative transmembrane and an intracellular domain. Here we demonstrate that T1
      transcription in mast cells and fibroblasts initiates at two different start
      sites which are 10.5 kb apart. The alternative first exons are both spliced to
      exon 2 which contains the translation start site. Northern blot analysis and
      primer extension experiments revealed that promoter usage is strictly cell type
      specific. T1 transcription in mast cells is initiated exclusively at the distal
      promoter, whereas in fibroblasts both the short and the long T1 mRNA start at the
      proximal promoter. Two GATA-1 elements were identified in the 5'-flanking region
      of the mast cell-specific distal exon 1.

PMID- 8550547
TI  - A binding site for SH3 domains targets dynamin to coated pits.
AB  - Dynamin is a GTPase that plays a critical role in the very early stages of
      endocytosis, regulating the scission of clathrin-coated and non-clathrin-coated
      pits from the plasma membrane. While the ligands through which dynamin exerts its
      in vivo effects are unknown, dynamin exhibits in vitro binding to several
      proteins containing Src homology 3 (SH3) domains, as well as to microtubules and
      anionic phospholipids, via a basic, proline-rich C-terminal domain. To begin to
      identify the in vivo binding partners of dynamin, we have examined by
      immunofluorescence the association of mutant and wild-type forms of dynamin with
      plasma membranes prepared by sonication of transiently transfected cells. Wild
      type dynamin was found almost exclusively in association with clathrin-containing
      domains. Binding to these regions was abolished by removal of a nine-amino acid
      sequence within the C-terminal domain encoding a candidate SH3 domain binding
      site. Binding did not require clathrin and resisted extraction at both high and
      low ionic strength, consistent with an interaction with an SH3 domain.
      Surprisingly, we also find that dynamin contains multiple regions involved in
      binding to nonclathrin-containing domains, including a 13-amino acid sequence
      directly upstream of the C-terminal domain. These observations suggest that a
      protein containing an SH3 domain is involved in recruiting dynamin to coated pits
      and provide the first evidence for a biological role for SH3 domains in dynamin
      function.

PMID- 8550548
TI  - Analysis of the growth and transformation suppressor domains of promyelocytic
      leukemia gene, PML.
AB  - The promyelocytic leukemia gene (PML) involved in the t(15;17) (q22;q12)
      translocation in acute promyelocytic leukemia is a growth suppressor. To
      elucidate the functional domains of PML, several mutants lacking the nuclear
      localization signal (PMLnls-), the dimerization domain (PMLdim-), the proline
      rich domain at the N-terminal (PMLpro-), the proline-rich RING finger motif
      (PMLpr-), the proline-rich RING finger B-box-1 (PML-prb-), the serine-proline
      rich domain at the C-terminal (PMLsp-), and the double mutant (PMLprb-nls-) have
      been constructed. Immunofluorescence staining of transiently transfected NIH3T3
      cells demonstrated that the RING finger motif, dimerization domain, and nuclear
      localization signal are all required for the formation of PML oncogenic domains
      (PODs). Immunofluorescence staining of transiently transfected GM637D human
      fibroblasts indicated that expression of PMLprb-, PM-Lnls-, and PMLprb-nls- led
      to a significant reduction or, in some cases, complete elimination of PODs.
      PMLdim-, PMLnls-, PMLpr-, PMLprb-, and PMLprb-nls- mutants were found to lose
      their ability to suppress transformation of NIH3T3 cells by activated neu, while
      PMLpro- and PMLsp- mutants did not. These results suggest that the ability of PML
      to form a POD is essential for suppression of growth and transformation.
      Furthermore, since PMLprb-, PMLnls-, and PMLprb-nls- mutants could block the
      suppression effect of wild-type PML on transformation of NIH3T3 cells by the neu
      oncogene, these PML mutants are potential dominant negative inhibitors of PML.
      Our study also suggests that the RING finger motif may interact with other
      nuclear proteins.

PMID- 8550549
TI  - Crystal structure of S-adenosylmethionine synthetase.
AB  - The structure of S-adenosylmethionine synthetase (MAT, ATP:L-methionine S
      adenosyltransferase, EC 2.5.1.6.) from Escherichia coli has been determined at
      3.0 A resolution by multiple isomorphous replacement using a uranium derivative
      and the selenomethionine form of the enzyme (SeMAT). The SeMAT data (9
      selenomethionine residues out of 383 amino acid residues) have been found to have
      a sufficient phasing power to determine the structure of the 42,000 molecular
      weight protein by combining them with the other heavy atom derivative data
      (multiple isomorphous replacement). The enzyme consists of four identical
      subunits; two subunits form a spherical tight dimer, and pairs of these dimers
      form a peanut-shaped tetrameric enzyme. Each pair dimer has two active sites
      which are located between the subunits. Each subunit consists of three domains
      that are related to each other by pseudo-3-fold symmetry. The essential divalent
      (Mg2+/Co2+) and monovalent (K+) metal ions and one of the product, Pi ions, were
      found in the active site from three separate structures.

PMID- 8550550
TI  - Specific interactions between the human RAD51 and RAD52 proteins.
AB  - Processing of DNA damage by the DNA double-strand break repair pathway in
      mammalian cells is accomplished by multiprotein complexes. However, the nature of
      these complexes and details of the molecular interactions are not fully
      understood. Interaction of the yeast RAD51 and RAD52 proteins plays a crucial
      role in yeast DNA homologous recombination and DNA double-strand break repair.
      Here, specific interactions between human RAD51 and RAD52 proteins are
      demonstrated both in vivo, using the yeast two-hybrid system and
      immunoprecipitation of insect cells co-infected with RAD51 and RAD52 recombinant
      viruses, and in vitro, using affinity chromatography with purified recombinant
      proteins. These results suggest that RAD52 may modulate the catalytic activities
      of RAD51 protein such as homologous pairing and strand exchange through a direct
      physical interaction. In addition, the domain in RAD52 that mediates this
      interaction was determined in vitro and in vivo. The RAD51-interacting region
      (amino acids 291-330) of the human RAD52 protein shows no homology with the yeast
      RAD52 protein, indicating that the interaction between RAD51 and RAD52 is species
      specific.

PMID- 8550551
TI  - The affinity of nuclear factor 1 for its DNA site is drastically reduced by
      nucleosome organization irrespective of its rotational or translational position.
AB  - A DNA-bending sequence has been used for in vitro reconstitution of nucleosomes
      in order to direct a nuclear factor 1 (NF-1) binding site into different
      nucleosome positions. By this strategy nucleosomes were obtained that had one of
      two rotational positions of the NF-1 binding site, one oriented toward the
      periphery and the other toward the histone octamer, translationally positioned 50
      and 45 base pairs, respectively, from the nucleosome dyad. The affinity of
      partially purified NF-1 for these nucleosomal targets was compared with its
      affinity for free DNA by dimethylsulfate methylation protection and DNase I
      footprinting assays. The binding affinity of NF-1 to all nucleosomal targets was
      reduced 100-300-fold compared with its affinity for free DNA. The two rotational
      settings of the NF-1 site showed the same binding affinity for NF-1 as did other
      nucleosome constructs in which the NF-1 binding site was translationally
      positioned from 10 to 40 base pairs from the nucleosome dyad. We conclude that
      the nucleosomal inhibition of NF-1 binding is an inherent characteristic of NF-1
      since another transcription factor, the glucocorticoid receptor, is able to bind
      to its DNA site in a nucleosome.

PMID- 8550552
TI  - Effect of tyrosine mutations on the kinase activity and transforming potential of
      an oncogenic human insulin-like growth factor I receptor.
AB  - The tyrosines in the cytoplasmic domain of an oncogenic human insulin-like growth
      factor I receptor (gag-IGFR) were systematically mutated to phenylalanines to
      investigate the role of those tyrosines in the enzymatic and biological function
      of the gag-IGFR. Our results indicate that tyrosines 1131, 1135, 1136, and 1221
      are important for the receptor protein-tyrosine kinase (PTK) activity. However,
      mutation of Tyr-1136 only slightly affects the kinase activity but dramatically
      reduces the transforming ability and overall substrate phosphorylation, in
      particular, annexin II, which is strongly phosphorylated by the gag-IGFR but not
      by the Phe-1136 mutant. Single mutation of either Tyr-943 or Tyr-950 resulted in
      significantly reduced phosphorylation of the receptor but not on its PTK activity
      or transforming ability. Tyr-950 together with its surrounding sequence is
      involved in mediating the interaction between the gag-IGFR and insulin receptor
      substrate 1. Our data also suggest that Tyr-1316 is involved in phosphorylation
      of phospholipase C-gamma, which is, however, not important for cell transforming
      activity. Overall, our study has identified several tyrosine residues of IGFR
      important for its PTK activity and substrate interaction. The transforming
      potential of the gag-IGFR correlates well with its ability to phosphorylate
      overall cellular substrates and to activate phosphatidylinositol 3-kinase via
      insulin receptor substrate 1.

PMID- 8550553
TI  - The active site specificity of the Yersinia protein-tyrosine phosphatase.
AB  - Yersinia protein-tyrosine phosphatase substrates have been synthesized employing
      an expedient methodology that incorporates phosphorylated non-amino acid residues
      into an active site-directed peptide. While the peptidic portion of these
      compounds serves an enzyme targeting role, the nonpeptidic component provides a
      critical assessment of the range of functionality that can be accommodated within
      the active site region. We have found that the Yersinia phosphatase hydrolyzes
      both L- and D-stereoisomers of phosphotyrosine in active site-directed peptides,
      with the former serving as a 10-fold more efficient substrate than the latter. In
      addition, this enzyme catalyzes the hydrolysis of a variety of aromatic and
      aliphatic phosphates. Indeed, a peptide bearing the achiral phosphotyrosine
      analog, phosphotyramine, is not only the most efficient substrate described in
      this study, it is also one of the most efficient substrates ever reported for the
      Yersinia phosphatase. Straight chain peptide-bound aliphatic phosphates of the
      general structure, (Glu)4-NH-(CH2)n-OPO3(2-) (n = 2-8), are also hydrolyzed,
      where the most efficient substrate contains seven methylene groups. Finally, a
      comparison of the substrate efficacy of the peptide-bound species with that of
      the corresponding non-peptidic analogs, reveals that the peptide component
      enhances kcat/Km by up to nearly 3 orders of magnitude.

PMID- 8550555
TI  - Precision substrate targeting of protein kinases. The cGMP- and cAMP-dependent
      protein kinases.
AB  - The cAMP-dependent (PKA) and cGMP-dependent protein kinases (PKG) share a strong
      primary sequence homology within their respective active site regions. Not
      surprisingly, these enzymes also exhibit overlapping substrate specificities, a
      feature that often interferes with efforts to elucidate their distinct biological
      roles. In this report, we demonstrate that PKA and PKG exhibit dramatically
      different behavior with respect to the phosphorylation of alpha-substituted
      alcohols. Although PKA will phosphorylate only residues that contain an alpha
      center configuration analogous to that found in L-serine, PKG utilizes residues
      that correspond to both L- and D-serine as substrates. The PKG/PKA selectivity of
      these substrates is the highest ever reported.

PMID- 8550554
TI  - c-Cbl is transiently tyrosine-phosphorylated, ubiquitinated, and membrane
      targeted following CSF-1 stimulation of macrophages.
AB  - Early colony stimulating factor-1 (CSF-1)-induced changes in the behavior of
      p120c-cbl in mouse BAC1.2F5 macrophages were investigated. p120c-cbl is
      associated with Grb2 in the cytoplasm of unstimulated cells. Following a 1-min
      stimulation with CSF-1, p120c-cbl becomes tyrosine-phosphorylated and associates
      with tyrosine-phosphorylated Shc and an unknown phosphotyrosyl protein (pp80).
      Simultaneously, it is ubiquitinated and translocated to the membrane. By 10 min
      of stimulation, this c-Cbl exhibits substantially decreased tyrosine
      phosphorylation and is de-ubiquitinated and relocated in the cytosol. However,
      the association of p120c-cbl with Shc persists for at least 60 min. These data
      indicate that signaling via the CSF-1R involves the transient modification of
      p120c-cbl and its recruitment as a complex to membrane.

PMID- 8550556
TI  - Is protein kinase substrate efficacy a reliable barometer for successful
      inhibitor design?
AB  - We have addressed the question of whether protein kinase substrate efficacy is a
      reliable barometer for successful inhibitor design by assessing the dependence of
      kcat and kcat/Km for eight separate alcohol-bearing residues on solvent
      viscosity. We have found that the Km for three structurally distinct primary
      alcohol-containing peptides overestimates the affinity that these species exhibit
      for the cAMP-dependent protein kinase. In all three cases, the rate-determining
      step is product release, and substrate binding is best described as rapid
      equilibrium. In contrast, peptides containing the following phosphorylatable
      residues all provide Km values that are accurate assessments of substrate
      affinity for the protein kinase: a secondary alcohol, a simple phenol, and a
      primary alcohol with a relatively long side chain. In the latter three instances,
      the rate-determining step is phosphoryl transfer. Finally, two aromatic alcohol
      containing residues that possess lipophilic side chains exhibit Michaelis
      constants that underestimate enzyme affinity. These results demonstrate that
      while it may be tempting to employ structural elements from the most efficient
      substrates (e.g. primary alcohols) for inhibitor design, less effective
      substrates may serve as a more accurate assessment of inhibitory success.

PMID- 8550557
TI  - Transcellular prostaglandin production following mast cell activation is mediated
      by proximal secretory phospholipase A2 and distal prostaglandin synthase 1.
AB  - Prostaglandins mediate many biological processes. Arachidonic acid, the common
      precursor for all prostaglandins, is released from membrane phospholipids by both
      secretory and cytoplasmic forms of phospholipase A2. Free arachidonate is
      converted to prostaglandin H2, the common precursor to all prostanoids, by
      prostaglandin synthase. Both mitogen-induced prostaglandin synthesis in
      fibroblasts and endotoxin-induced prostaglandin synthesis in macrophages require
      expression of the inducible prostaglandin synthase-2; arachidonate released in
      these contexts is unavailable to prostaglandin synthase-1 constitutively present
      in fibroblasts or macrophages. In contrast to the results for fibroblasts and
      macrophages, prostaglandin synthesis by activated mast cells is mediated by
      prostaglandin synthase-1. Mast cell activation also provokes release of secretory
      phospholipase A2 (sPLA2). We now demonstrate that sPLA2 released from activated
      mast cells can mobilize arachidonate from distal Swiss 3T3 cells. This
      arachidonate is then used by prostaglandin synthase-1 present in 3T3 cells for
      prostaglandin synthesis. We thus distinguish two pathways for prostaglandin
      synthesis: (i) an intracellular pathway by which arachidonate released following
      ligand stimulation is made available only to prostaglandin synthase-2, and (ii) a
      transcellular pathway by which sPLA2 of proximal cells mobilizes, in distal
      cells, arachidonate available to prostaglandin synthase-1. Molecular and
      pharmacologic approaches to modulating prostaglandin-mediated events will differ
      for these two pathways.

PMID- 8550558
TI  - The oxidative metabolism of glutamine. A modulator of reactive oxygen
      intermediate-mediated cytotoxicity of tumor necrosis factor in L929 fibrosarcoma
      cells.
AB  - Treatment of the mouse fibrosarcoma cell line L929 with tumor necrosis factor
      (TNF) induces necrotic cell death. A crucial step in the cytotoxic action
      mechanism of TNF involves perturbation of mitochondrial functions leading to the
      formation of reactive oxygen intermediates (ROI). L929 cells have energy
      requirements adapted to a high proliferation rate. Glutamine (Gln) is utilized as
      a major energy source and drives mitochondrial ATP formation, while glucose is
      mainly converted to lactate through glycolysis. We investigated the role of the
      bioenergetic pathways involved in substrate utilization on the cytotoxic action
      of TNF and established a link between Gln oxidation and TNF-induced mitochondrial
      distress. Omission of Gln from the medium desensitizes the cells to TNF
      cytotoxicity, while the lack of glucose in the medium does not alter the TNF
      response. Sudden depletion of Gln from the culture medium results in a sharp
      decline in mitochondrial respiration in the cells, which might explain the
      decreased TNF responsiveness. However, when L929 cells are adapted to long term
      growth under conditions without Gln, these so-called L929/Gln- cells have
      restored respiration, but they still display a decreased sensitivity to TNF
      cytotoxicity. Thus the TNF responsiveness of L929 cells depends on bioenergetic
      reactions that are specifically involved in the oxidation of Gln. This is further
      confirmed by the desensitizing effect of specific inhibitors of these Gln-linked
      enzyme reactions on TNF cytotoxicity in the parental cells, but not in the
      L929/Gln- cells. Analysis of the induction of mitochondrial ROI formation by TNF
      in parental and L929/Gln- cells suggests that the effect of Gln on the
      sensitivity to TNF cytotoxicity involves a mechanism that renders the
      mitochondria more susceptible to TNF-induced mediators, resulting in enhanced ROI
      production and accelerated cytotoxicity.

PMID- 8550559
TI  - Identification and characterization of the linear IS3 molecules generated by
      staggered breaks.
AB  - Insertion sequences IS3 encodes two, out-of-phase, overlapping open reading
      frames, orfA and orfB. The OrfAB transframe protein that is IS3 transposase is
      produced by -1 translational frameshifting between orfA and orfB. Efficient
      production of the IS3 transposase in the cells harboring the IS3-carrying plasmid
      has been shown to generate miniplasmids as well as characteristic minicircles,
      called IS3 circles, consisting of the entire IS3 sequence and one of the 3-base
      pair sequences flanking IS3 in the parental plasmid. Here, we show that the IS3
      transposase also generates the linear molecules of IS3 with 3-nucleotide
      overhangs at the 5'-ends. The nucleotide sequences of the overhangs are the same
      as those flanking IS3 in the parental plasmid, suggesting that the linear IS3
      molecules are generated from the parental plasmid DNA by staggered double strand
      breaks at the end regions of IS3. The linear IS3 molecules are likely to be the
      early intermediates in the transposition reaction, which proceeds in a non
      replicative manner.

PMID- 8550560
TI  - Hepatic overexpression of insulin-like growth factor-II in adulthood increases
      basal and insulin-stimulated glucose disposal in conscious mice.
AB  - The physiological role of circulating insulin-like growth factor-II (IGF-II) in
      adult humans is poorly understood. We recently generated an IGF-II transgenic
      murine model of persistent IGF-II production (plasma IGF-II approximately 30-fold
      increased above normal) through over-expression of the transgene driven by the
      major urinary protein promoter (Rinderknecht, E., and Humbel, R. E. (1978) J.
      Biol. Chem. 269, 13779-13784). To determine whether in vivo insulin action is
      improved in these transgenic mice, we performed euglycemic insulin (18
      milliunits/kg.min) clamp studies in conscious IGF-II transgenic and in age- and
      weight-matched control mice. Plasma glucose and insulin concentrations were
      significantly lower in the IGF-II transgenic compared with both control grouoff
      Despite decreased plasma glucose concentration, basal hepatic glucose production
      (HGP) and glucose clearance were increased. During the insulin clamp studies in
      IGF-II transgenic mice compared with control mice (a) the rates of glucose
      infusion and glucose uptake were increased by approximately by 65 and
      approximately 55%, respectively; (b) glycolysis was increased by approximately
      12% while glycogen synthesis was approximately 2-fold higher; (c) while the
      suppression of plasma free fatty acid was similar, the increment in plasma
      lactate concentration was significantly higher; (d) although HGP was similarly
      inhibited by insulin, phosphoenolpyruvate gluconeogenesis was enhanced and
      accounted for a larger portion of HGP (64% versus approximately 40% in control
      mice). Our data suggest that the persistence of circulating IGF-II in adult mice
      to levels commonly observed in adult humans (50-70 nM) causes a marked
      improvement in peripheral (skeletal muscle) insulin action, which is not due to
      changes in body composition. These results suggest that circulating IGF-II may
      exert a regulatory role on insulin sensitivity and body composition in humans.

PMID- 8550561
TI  - Biosynthesis of N-acetylsphingosine by platelet-activating factor: sphingosine
      CoA-independent transacetylase in HL-60 cels.
AB  - We have previously identified a novel CoA-independent transacetylase in the
      membrane fraction of HL-60 cells that transfers the acetate group from platelet
      activating factor (PAF) to a variety of lysophospholipid acceptors (Lee, T.-c.,
      Uemura, Y., and Snyder, F. (1992) J. Biol. Chem. 267, 19992-20001). In the
      present study, we demonstrate that a similar transacetylase can transfer the
      acetate group from PAF to sphingosine forming N-acetylsphingosine (C2-ceramide).
      The chemical structure of the reaction product, C3-ceramide, was established by
      its identical Rf value with authentic C2-ceramide standard on thin-layer plate,
      sensitivity to acid treatment, resistance to alkaline hydrolysis, and ability to
      form the C2-ceramide dibenzoate derivative. Nonspecific transfer of the acetate
      from PAF to sphingosine in the absence of enzyme and nonlinearity of the reaction
      rates were rectified by complexing sphingosine to bovine serum albumin in a 1:1
      molar ratio. Under these conditions, the apparent Km for PAF is 5.4 microM, which
      is in the same range as the Km (12.0 microM) when lysoplasmalogen is the acetate
      acceptor. PAF:sphingosine transacetylase has a narrow substrate specificity and
      strict stereochemical configuration requirements. Ceramide,
      sphingosylphosphocholine, stearylamine, sphingosine 1-phosphate, or sphingomyelin
      are not substrates, whereas sphinganine has a limited capacity to accept the
      acetate from PAF. Also, only the naturally synthesized D-erythroisomer but not
      the synthetic L-erythro-, D-threo-, or L-threosiomers of sphingosine can serve as
      a substrate. PAF transacetylase activity is widely distributed among several
      tissues and may involve histidine and cysteine for its catalytic activity due to
      inhibitory effects to the enzyme by diethyl pyrocarbonate and N-ethylmaleimide,
      respectively. C2-ceramide is produced via PAF:sphingosine transacetylase, and
      physiological levels of C2-ceramide are detected in both undifferentiated and
      differentiated intact HL-60 cells. Collectively, because C2-ceramide has many
      biological activities that differ from that of PAF and sphingosine, the CoA
      independent, PAF-dependent transacetylase serves as a modifier of PAF, and
      sphingosine functions by generating a variant lipid mediator, C2-ceramide.

PMID- 8550562
TI  - Integrin-associated protein is a receptor for the C-terminal domain of
      thrombospondin.
AB  - The C-terminal "cell-binding domain" (CBD) of thrombospondin-1 (TS1) is a binding
      site for many cell types. Cell-binding peptides based on the sequence RFYVVM from
      the CBD of TS1 affinity label a 52-kDa cell surface glycoprotein, which we show
      is integrin-associated protein (IAP or CD47). IAP associates with alpha v beta 3
      and thereby modulates the activity of several integrins. Cells that express IAP
      bind strongly to TS1, the CBD, and its active cell-binding peptides while IAP
      negative cells do not. The 52-kDa protein is affinity labeled on IAP-positive but
      not IAP-negative cells, and monoclonal antibodies against IAP specifically
      immunoprecipitate the affinity-labeled 52-kDa protein from lysates of IAP
      positive cells. Consistent with the association of IAP with alpha v beta 3
      integrin, the labeled 52-kDa protein is immunoprecipitated by an anti-alpha v
      beta 3 antibody. Endothelial cells exhibit chemotaxis toward TS1 (at
      concentrations above 10 nM) and RFYVVM peptides. Chemotaxis to both agents is
      specifically inhibited by a function blocking anti-IAP monoclonal antibody. These
      data establish IAP (CD47) as a receptor for the CBD of TS1 and suggest a
      mechanism for the well established effects of the CBD on cell motility.

PMID- 8550563
TI  - Transcriptional suppression of the transferrin gene by hypolipidemic peroxisome
      proliferators.
AB  - Activation of gene expression by hypolipidemic peroxisome proliferators (e.g.
      native and substituted long chain fatty acids, aryloxyalkanoic fibrate drugs) is
      accompanied by transcriptional suppression of liver transferrin gene in treated
      animals or human hepatoma cell line. Transcriptional suppression of liver
      transferrin by hypolipidemic peroxisome proliferators results from (a)
      displacement of hepatic nuclear factor (HNF)-4 from the transferrin promoter by
      nonproductive binding of the peroxisome proliferator-activated receptor-retinoic
      acid X receptor heterodimer to the (-76/-52) PRI promoter element of the human
      transferrin gene and (b) suppression of liver HNF-4 gene expression by
      hypolipidemic peroxisome proliferators with a concomitant decrease in its
      availability for binding to the transferrin PRI promoter element. HNF-4 gene
      suppression and its displacement from the transferrin promoter result in
      eliminating HNF-4-enhanced transcription of transferrin. Liver transferrin
      suppression by hypolipidemic peroxisome proliferators may result in reduced iron
      availability as well as modulation of transferrin-induced differentiation
      processes. Transcriptional suppression of HNF-4-enhanced liver genes (e.g.
      apolipoprotein C-III, transferrin) may complement the pleiotropic biological
      effect exerted by hypolipidemic peroxisome proliferators.

PMID- 8550564
TI  - CXC chemokines bind to unique sets of selectivity determinants that can function
      independently and are broadly distributed on multiple domains of human
      interleukin-8 receptor B. Determinants of high affinity binding and receptor
      activation are distinct.
AB  - Human interleukin-8 receptors A (IL-8RA) and B (IL-8RB) are seven-transmembrane
      domain (TMD) neutrophil chemokine receptors with similar sequences (77% amino
      acid identity) and similar G protein selectivity, but markedly different
      selectivity for CXC chemokines. IL-8RB is selective for IL-8, growth-related
      oncogene alpha (GRO alpha) and neutrophil-activating peptide-2 (NAP-2), whereas
      IL-8RA is selective only for IL-8. To identify selectivity determinants, we made
      eight chimeric receptors exchanging: 1) the three main regions of sequence
      divergence between IL-8RA and IL-8RB (the N-terminal segment before TMD1, the
      region from TMD4 to the end of the second extracellular (e2) loop, and the C
      terminal tail), and 2) the N-terminal segment of CC chemokine receptor 1, which
      does not bind CXC chemokines. Chimeras were tested by direct 125I-IL-8, 125I-GRO
      alpha, and 125I-NAP-2 binding, heterologous competition binding, and calcium flux
      assays using human embryonic kidney 293 cells stably transfected with receptor
      DNAs. The following results were obtained: 1) chimeric receptors had binding
      sites for IL-8, GRO alpha and NAP-2 distinct from those on IL-8RA and IL-8RB; 2)
      IL-8, GRO alpha and NAP-2 bound to overlapping but distinct sites that mapped
      differentially to multiple domains on IL-8RB; 3) high affinity radioligand
      binding and high agonist potency were separable functions for IL-8, GRO alpha and
      NAP-2, suggesting that the determinants of high affinity binding may not be
      critical for receptor activation; and 4) determinants of GRO alpha and NAP-2
      selectivity were found in both the N-terminal segment before TMD1 and the region
      from TMD4 to the end of the e2 loop of IL-8RB, and functioned independently of
      each other. Stated reciprocally, the N-terminal segment of IL-8RA was not a
      dominant selectivity determinant. These data suggest that both narrow and broad
      spectrum chemokine antagonists can be developed to block functions mediated by IL
      8RB.

PMID- 8550565
TI  - Ras interaction with two distinct binding domains in Raf-1 may be required for
      Ras transformation.
AB  - Although Raf-1 is a critical Ras effector target, how Ras mediates Raf-1
      activation remains unresolved. Raf-1 residues 55-131 define a Ras-binding domain
      essential for Raf-1 activation. Therefore, our identification of a second Ras
      binding site in the Raf-1 cysteine-rich domain (residues 139-184) was unexpected
      and suggested a more complex role for Ras in Raf-1 activation. Both Ras
      recognition domains preferentially associate with Ras-GTP. Therefore, mutations
      that impair Ras activity by perturbing regions that distinguish Ras-GDP from Ras
      GTP (switch I and II) may disrupt interactions with either Raf-1-binding domain.
      We observed that mutations of Ras that impaired Ras transformation by perturbing
      its switch I (T35A and E37G) or switch II (G60A and Y64W) domain preferentially
      diminished binding to Raf-1-(55-131) or the Raf-1 cysteine-rich domain,
      respectively. Thus, these Ras-binding domains recognize distinct Ras-GTP
      determinants, and both may be essential for Ras transforming activity. Finally,
      since Ha-Ras T35A and E37G mutations prevent Ras interaction with full-length Raf
      1, we suggest that Raf-Cys is a cryptic binding site that is unmasked upon Ras
      interaction with Raf-1-(55-131).

PMID- 8550566
TI  - Ligand-induced conformational changes in the apical domain of the chaperonin
      GroEL.
AB  - Although the role of nucleotides in the catalytic cycle of the GroESL chaperonin
      system has been extensively studied, the molecular effects of nucleotides in
      modulating exposure of sites on GroEL has not been thoroughly investigated. We
      report here that nucleotides (ATP, ADP, or adenosine 5'-(beta, gamma
      imino)triphosphate) in the presence of Mg2+ make the oligomer selectively
      sensitive to trypsin proteolysis in a fashion suggesting conformational changes
      in the monomers of one heptameric ring. The site of proteolysis in the monomer
      that is exposed upon nucleotide binding by the oligomer is in the apical domain
      (Arg-268). Further, complexes of GroEL with GroES or rhodanese display the same
      sensitivity to proteolysis, unlike the GroEL-GroES-rhodanese complex, which is
      protected from proteolysis. The influence of various cations on trypsin
      proteolysis is investigated to elucidate the differential effects that monovalent
      and divalent cations have on the oligomeric structure of the chaperonin. These
      results are discussed in relation to the molecular basis for the chaperonin
      activity.

PMID- 8550567
TI  - Covalent binding of peptides to the N-terminal hydrophobic region of cardiac
      troponin C has limited effects on function.
AB  - Exposure of an N-terminal hydrophobic region in troponin C is thought to be
      important for the regulation of contraction in striated muscle. To test this
      hypothesis, single Cys residues were engineered at positions 45, 81, 84, or 85 in
      the N-terminal hydrophobic region of cardiac troponin C (cTnC) to provide
      specific sites for attachment of blocking groups. A synthetic peptide, Ac-Val-Arg
      Ala-Ile-Gly-Lys-Leu-Ser-Ser, or biotin was coupled to these Cys residues, and the
      covalent adducts were tested for activity in TnC-extracted myofibrils. Covalent
      modification of cTnC(C45) had no effect on maximal myofibril ATPase activity.
      Greatly decreased myofibril ATPase activity (70-80% inhibited) resulted when the
      peptide was conjugated to Cys-81 in cTnC(C81), while a lesser degree of
      inhibition (10-25% inhibited) resulted from covalent modification of cTnC(C84)
      and cTnC(C85). Inhibition was not due to an altered affinity of the
      cTnC(C81)/peptide conjugate for the myofibrils, and the Ca2+ dependence of ATPase
      activity was essentially identical to the unmodified protein. Thus, a subregion
      of the N-terminal hydrophobic region in cTnC is sensitive to disruption, while
      other regions are less important or can adapt to rather bulky blocking groups.
      The data suggest that Ca(2+)-sensitizing drugs may bind to the N-terminal
      hydrophobic region on cTnC but not interfere with transmission of the Ca2+
      signal.

PMID- 8550568
TI  - Molecular cloning, splice variants, expression, and purification of phospholipase
      C-delta 4.
AB  - Complementary DNAs encoding a previously unidentified phosphoinositide-specific
      phospholipase C (PLC) isozyme were cloned from a rat brain cDNA library by the
      polymerase chain reaction with degenerate oligonucleotide primers based on
      sequences common to three known delta-type PLC isozymes. The encoded polypeptide
      contains 772 amino acids (calculated molecular mass, 88,966 daltons) and is
      similar in primary structure to delta-type PLC isozymes, with overall sequence
      identities of 45% to PLC-delta 1, 72% to PLC-delta 2, and 47% to PLC-delta 3.
      Thus, the new PLC isozyme was named PLC-delta 4. Recombinant PLC-delta 4 was
      purified from extracts of HeLa cells that had been infected with vaccinia virus
      containing the corresponding cDNA. The purified protein exhibited an apparent
      molecular mass of 90 kDa on SDS-polyacrylamide gels. The specific activity of PLC
      delta 4 and its dependence on Ca2+ were similar to those of PLC-delta 1. The
      distribution of PLC-delta 4 in 16 different rat tissues was studied by immunoblot
      analysis with PLC-delta 4-specific antibodies of fractions obtained after an
      enzyme-enrichment procedure. The 90-kDa immunoreactive protein was detected
      unambiguously in only eight tissues and was present at concentrations that were
      low compared to those of other major PLC isozymes. A 93-kDa immunoreactive
      protein was also prominent in testis but was not detected in the other seven
      positive tissues. The 93-kDa enzyme appears to be derived from a splice variant
      of the mRNA that encodes the 90-kDa PLC-delta 4 and contains an additional 32
      amino acids between the X and Y catalytic domains. Splice variants have not
      previously been detected for delta-type PLC isozymes.

PMID- 8550569
TI  - Endocytic properties of the M-type 180-kDa receptor for secretory phospholipases
      A2.
AB  - Endocytic properties of the M-type 180-kDa receptor for secretory phospholipases
      A2 (sPLA2) were first investigated in rabbit myocytes that express it at high
      levels. Internalization of the receptor was shown to be clathrin-coated pit
      mediated, rapid (ke = 0.1 min-1), and ligand-independent. The signal sequence for
      internalization was then identified upon transient and stable expression of
      various receptor constructs with mutated cytoplasmic sequences. Analysis of the
      internalization efficiency of the mutants suggested that the NSYY motif encodes
      the major endocytic signal, with the distal tyrosine residue playing the key
      role. Amino acid substitutions at the putative casein kinase II phosphorylation
      site of the receptor did not affect internalization. A chimeric protein composed
      of the extracellular and transmembrane domains of the rabbit sPLA2 receptor and
      of the cytoplasmic domain of the structurally homologous human macrophage mannose
      receptor retained the high affinity for sPLA2 and was internalization competent,
      exhibiting 50% endocytic activity of the M-type sPLA2 receptor. The results
      indicate the compatibility of the structural domains of the two parent proteins
      and provide evidence for the interchangeable character of their internalization
      signals.

PMID- 8550570
TI  - Dephosphorylation of catalytic subunit of cAMP-dependent protein kinase at Thr
      197 by a cellular protein phosphatase and by purified protein phosphatase-2A.
AB  - Thr-197 phosphate is essential for optimal activity of the catalytic (C) subunit
      of cAMP-dependent protein kinase enzyme, and, in the C subunit crystal structure,
      it is buried in a cationic pocket formed by the side chains of His-87, Arg-165,
      Lys-189, and Thr-195. Because of its apparent role in stabilizing the active
      conformation of C subunit and its resistance to several phosphatases, the
      phosphate on Thr-197 has been assumed to be metabolically stable. We now show
      that this phosphate can be removed from C subunit by a protein phosphatase
      activity extracted from S49 mouse lymphoma cells or by purified protein
      phosphatase-2A (PP-2A) with concomitant loss of enzymatic activity. By anion
      exchange chromatography, inhibitor sensitivity, and relative activity against
      glycogen phosphorylase a and C subunit as substrates, the cellular phosphatase
      resembled a multimeric form of PP-2A. PP-1 was ineffective against native C
      subunit, but it was able to dephosphorylate Thr-197 in urea-treated C subunit.
      Accessibility of Thr-197 phosphate to the cellular phosphatase was enhanced by
      storage of C subunit in a phosphate-free buffer or by inclusion of modest
      concentrations of urea in the reactions and was reduced by salt concentrations in
      the physiological range and/or by amino-terminal myristoylation. It is concluded
      that a multimeric form of PP-2A or a closely related enzyme from cell extracts is
      capable of removing the Thr-197 phosphate from native C subunit in vitro and
      could account for significant turnover of this phosphate in intact cells.

PMID- 8550571
TI  - Affinity, specificity, and kinetics of the interaction of the SHC phosphotyrosine
      binding domain with asparagine-X-X-phosphotyrosine motifs of growth factor
      receptors.
AB  - The phosphotyrosine binding (PTB) domain specifically binds to tyrosine
      phosphorylated proteins, but differs in structure and mechanism of action from
      the SH2 domain family. We quantitated the affinity, specificity, and kinetics of
      the interaction of the SHC PTB domain with a sequence motif, asparagine-X-X
      phosphotyrosine (NXX(pY)), found in several receptor tyrosine kinases and
      oncogenic proteins. PTB domain-mediated interaction with the NXX(pY) motif of c
      ErbB2 was characterized by similar overall affinity but slower kinetics than that
      reported for SH2 domains. This suggested that unlike SH2 domains, PTB domains may
      not rapidly exchange among associated proteins. Furthermore, when directly and
      quantitatively compared, PTB domain binding specificity did not significantly
      overlap with a panel of seven SH2 domains. Thus, signaling pathways involving PTB
      and SH2 domain-mediated interactions can be regulated separately. Finally, our
      data define the minimal SHC PTB domain binding motif as NXX(pY), not NPX(pY) as
      suggested by other authors, and suggest a high affinity motif, hydrophobic
      residue-(D/E)-N-X-X-pY-(W/F), found in the Trk and ErbB receptor tyrosine kinase
      families. We conclude that PTB domains mediate specific protein-protein
      interactions independent from those mediated by SH2 domains.

PMID- 8550572
TI  - Amperometric detection of quantal secretion from patch-clamped rat pancreatic
      beta-cells.
AB  - Serotonin (5-HT) is taken up in insulin granules and co-released with insulin on
      stimulation of pancreatic islet beta-cells. Based on these observations, we have
      used microcarbon fiber amperometry to examine secretogogue-induced 5-HT release
      from rat beta-cells preloaded for 4-16 h with 5-HT and then exposed to a bath
      solution containing 10 microM forskolin. In response to local application of KCl
      (60 mM) or tolbutamide (50-200 microM), we recorded barrages of amperometric
      events. Each amperometric event consisted of a short pulse of current measurable
      at electrode voltages that catalyze 5-HT oxidation. With either secretogogue,
      release was calcium-dependent. On combining amperometry with perforated patch
      whole-cell recording, we found that barrages of such events were well coupled in
      time and graded in intensity with depolarization-induced Ca2+ currents and well
      correlated with increases in membrane capacitance. In cell-attached patch
      recording, amperometric events evoked by application of tolbutamide followed the
      closure of ATP-sensitive K+ channels and coincided with the onset of electrical
      activity. These experiments suggest that amperometry is a useful technique for
      studying, in real time, the dynamic aspects of stimulus-secretion coupling in
      beta-cells. Their performance was facilitated by the design of a new carbon fiber
      electrode (ProCFE) described within.

PMID- 8550573
TI  - The type I interferon receptor mediates tyrosine phosphorylation of insulin
      receptor substrate 2.
AB  - Binding of interferon alpha (IFN alpha) to its receptor induces activation of the
      Tyk-2 and Jak-1 tyrosine kinases and tyrosine phosphorylation of multiple
      downstream signaling elements, including the Stat components of the interferon
      stimulated gene factor 3 (ISGF-3). IFN alpha also induces tyrosine
      phosphorylation of IRS-1, the principle substrate of the insulin receptor. In
      this study we demonstrate that various Type I IFNs rapidly stimulate tyrosine
      phosphorylation of IRS-2. This is significant since IRS-2 is the major IRS
      protein found in hematopoietic cells. The IFN alpha-induced phosphorylated form
      of IRS-2 associates with the p85 regulatory subunit of the phosphatidylinositol
      3'-kinase, suggesting that this kinase participates in an IFN alpha-signaling
      cascade downstream of IRS-2. We also provide evidence for an interaction of IRS-2
      with Tyk-2, suggesting that Tyk-2 is the kinase that phosphorylates this protein
      during IFN alpha stimulation. A conserved region in the pleckstrin homology
      domain of IRS-2 may be required for the interaction of IRS-2 with Tyk-2, as shown
      by the selective binding of glutathione S-transferase (GST) fusion proteins
      containing the IRS-2-IH1PH or IRS-1-IH1PH domains to Tyk-2 but not other Janus
      kinases in vitro.

PMID- 8550574
TI  - Increase of flux control of cytochrome c oxidase in copper-deficient mottled
      brindled mice.
AB  - The brindled mottled mouse (Mobr), an animal model of the Menkes' copper
      deficiency syndrome, was used for the investigation of changes in respiratory
      flux control associated with cytochrome c oxidase deficiency in muscle. Enzymatic
      analysis of cardiac and skeletal muscles showed an approximately 2-fold decrease
      in cytochrome c oxidase activity of brindled mutants in both types of muscles as
      compared with controls. The activities of NADH-cytochrome c oxidoreductase
      (respiratory chain segment I-III) and succinate-cytochrome c oxidoreductase
      (segment II-III) were normal. Assessment of mitochondrial respiratory function
      was performed using chemically skinned musculus quadriceps or heart muscle fibers
      isolated from control and brindled mottled mice. In skeletal muscle, there was no
      difference found in maximal rates of respiration. In the Mobr hearts, this
      parameter was slightly lower than control. Alternately, the determination of flux
      control coefficients of cytochrome c oxidase performed by a step by step
      inhibition of respiration with increasing concentrations of azide or cyanide
      revealed significantly sharper inhibition curves for brindled mice than for
      control, indicating more than 2-fold elevated flux control coefficients of
      cytochrome c oxidase. This investigation proved essential in characterizing the
      metabolic effect of a cytochrome c oxidase deficiency. We conclude, therefore,
      that application of metabolic control analysis can be a valuable approach to
      study defects of mitochondrial oxidative phosphorylation.

PMID- 8550575
TI  - Substitutions of proline 42 to alanine and methionine 46 to asparagine around the
      RGD domain of the neurotoxin dendroaspin alter its preferential antagonism to
      that resembling the disintegrin elegantin.
AB  - Previous studies have shown that the neurotoxin dendroaspin and the disintegrin
      kistrin, which show little overall sequence homology but similar residues around
      RGD (PRGDMP), preferentially inhibited platelet adhesion to fibrinogen. In
      contrast, the elegantin which has different amino acids around RGD (ARGDNP)
      preferentially inhibited platelet adhesion to fibronectin. To investigate further
      the role of amino acids around RGD in disintegrins, we have constructed the genes
      of a wild-type and of two mutant dendroaspins with substitutions around the RGD,
      namely [Asn46]- and [Ala42,Asn46]-dendroaspins. Proteins were expressed in
      Escherichia coli as glutathione S-transferase fusion recombinants and purified to
      homogeneity by affinity chromatography and reversed phase high performance liquid
      chromatography. Platelet aggregation studies revealed that wild-type dendroaspin
      showed an IC50 value similar to that of native dendroaspin, with [Ala42,Asn46]
      dendroaspin showing an IC50 value similar to that of elegantin. Interestingly, in
      platelet adhesion assays, the mutants showed a progressive shift in inhibitory
      preference, in particular, [Ala42,Asn46]dendroaspin showed nearly identical
      behavior as elegantin when fibronectin was the immobilized ligand (IC50 = 0.33
      microM and 0.6 microM, respectively, compared with 20 microM for native
      dendroaspin). Native and recombinant wild-type dendroaspin bound to a single
      class of binding site exhibiting a Kd = 67 nM; [Asn46]- and
      [Ala42,Asn46]dendroaspins, however, both produced biphasic isotherms with Kd
      values = 87 nM and 361 nM for [Asn46]dendroaspin and 33 nM and 371 nM for
      [Ala42,Asn46]dendroaspin, which are close to those of elegantin (Kd values = 18
      nM and 179 nM). These studies prove that the amino acids flanking RGD provide an
      extended locus that regulate the affinity and selectivity of RGD protein
      dendroaspin.

PMID- 8550576
TI  - Sphingosine and sphingosine 1-phosphate differentially modulate platelet-derived
      growth factor-BB-induced Ca2+ signaling in transformed oligodendrocytes.
AB  - The roles of sphingosine and sphingosine 1-phosphate in Ca2+ signaling following
      platelet-derived growth factor (PDGF) receptor stimulation were investigated in
      the oligodendrocyte cell line CEINGE cl3, using single-cell fura-2
      microfluorimetry and videoimaging. Two different Ca2+ responses were observed,
      which differed in their delays and kinetics. The first response, which occurred
      after a shorter delay, exhibited a single Ca2+ peak often followed by a plateau,
      while the second type of response was characterized by a longer delay and by Ca2+
      spikes with different frequencies and amplitudes. The latter phenomenon was never
      observed after stimulation of G protein-coupled receptors for ATP, ET-1, and BK.
      The incubation with the inhibitor of sphingosine kinase, DL-threo
      dihydrosphingosine, significantly increased the percentage of cells responding to
      PDGF-BB exposure with Ca2+ spikes (87 versus 47%), while it did not modify the
      Ca2+ response elicited by exposure to ATP, ET-1, or BK. Exposure to exogenous 10
      microM sphingosine or 1 microM sphingosine 1-phosphate produced oscillatory and
      non-oscillatory Ca2+ responses, respectively, similar to those elicited by PDGF
      BB. A second application of PDGF-BB, 30 min after the first, was normally
      ineffective in producing a Ca2+ response. However, if the second exposure was
      preceded by the inhibition of sphingosine 1-phosphate formation, an oscillatory
      Ca2+ response occurred in all cells. We conclude that intracellular levels of
      sphingosine and sphingosine 1-phosphate may differentially modulate Ca2+
      signaling triggered by PDGF receptor stimulation in CEINGE cl3-transformed
      oligodendrocytes.

PMID- 8550577
TI  - Isolation, characterization, and partial purification of a novel ubiquitin
      protein ligase, E3. Targeting of protein substrates via multiple and distinct
      recognition signals and conjugating enzymes.
AB  - Degradation of a protein via the ubiquitin system involves two discrete steps,
      conjugation of ubiquitin to the substrate and degradation of the adduct.
      Conjugation follows a three-step mechanism. First, ubiquitin is activated by the
      ubiquitin-activating enzyme, E1. Following activation, one of several E2 enzymes
      (ubiquitin-carrier proteins or ubiquitin-conjugating enzymes, UBCs) transfers
      ubiquitin from E1 to the protein substrate that is bound to one of several
      ubiquitin-protein ligases, E3s. These enzymes catalyze the last step in the
      process, covalent attachment of ubiquitin to the protein substrate. The binding
      of the substrate to E3 is specific and implies that E3s play a major role in
      recognition and selection of proteins for conjugation and subsequent degradation.
      So far, only a few ligases have been identified, and it is clear that many more
      have not been discovered yet. Here, we describe a novel ligase that is involved
      in the conjugation and degradation of non "N-end rule" protein substrates such as
      actin, troponin T, and MyoD. This substrate specificity suggests that the enzyme
      may be involved in degradation of muscle proteins. The ligase acts in concert
      with E2-F1, a previously described non N-end rule UBC. Interestingly, it is also
      involved in targeting lysozyme, a bona fide N-end substrate that is recognized by
      E3 alpha and E2-14 kDa. The novel ligase recognizes lysozyme via a signal(s) that
      is distinct from the N-terminal residue of the protein. Thus, it appears that
      certain proteins can be targeted via multiple recognition motifs and distinct
      pairs of conjugating enzymes. We have purified the ligase approximately 200-fold
      and demonstrated that it is different from other known E3s, including E3
      alpha/UBR1, E3 beta, and E6-AP. The native enzyme has an apparent molecular mass
      of approximately 550 kDa and appears to be a homodimer. Because of its unusual
      size, we designated this novel ligase E3L (large). E3L contains an -SH group that
      is essential for its activity. Like several recently described E3 enzymes,
      including E6-AP and the ligase involved in the processing of p105, the NF-kappa B
      precursor, the novel ligase is found in mammalian tissues but not in wheat germ.

PMID- 8550578
TI  - Nucleotide binding by the epidermal growth factor receptor protein-tyrosine
      kinase. Trinitrophenyl-ATP as a spectroscopic probe.
AB  - The nucleotide binding properties of the epidermal growth factor (EGF) receptor
      protein-tyrosine kinase were investigated with the fluorescent nucleotide analog
      2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). TNP-ATP was
      found to be an active substrate for the autophosphorylation reaction of the
      recombinant EGF receptor protein-tyrosine kinase domain (TKD). Whereas the Vmax
      for the TNP-ATP-dependent autophosphorylation reaction was approximately 200-fold
      lower than that of ATP, the Km for this reaction was similar to that observed
      with ATP. The nucleotide analog was also shown to be an inhibitor of the ATP
      dependent autophosphorylation and substrate phosphorylation reactions of the TKD.
      Spectroscopic studies demonstrated both a high affinity binding of TNP-ATP to the
      recombinant TKD and a markedly enhanced fluorescence of the bound nucleotide
      analog. The fluorescence of enzyme-bound TNP-ATP was attenuated in the presence
      of ATP, which enabled determination of the dissociation constants for both ATP
      and the Mn2+ complex of ATP. A truncated form of the EGF receptor TKD lacking the
      C-terminal autophosphorylation domain exhibited an enhanced affinity for TNP-ATP,
      which indicated that the autophosphorylation domain occupied the peptide
      substrate binding site of the TKD and modulated the binding of the nucleotide
      substrates.

PMID- 8550579
TI  - Molecular cloning, heterologous expression, and characterization of human
      glyoxalase II.
AB  - A clone encoding glyoxalase II has been isolated from a human adult liver cDNA
      library. The sequence of 1011 base pairs consists of a full-length coding region
      of 780 base pairs, corresponding to a protein with a calculated molecular mass of
      28,861 daltons. Identities (50-60%) were found to partial 5' and 3' cDNA
      sequences from Arabidopsis thaliana as well as within a limited region of
      glutathione transferase I cDNA from corn. A vector was constructed for
      heterologous expression of glyoxalase II in Escherichia coli. For optimal yield
      of enzyme, silent random mutations were introduced in the 5' coding region of the
      cDNA. A yield of 25 mg of glyoxalase II per liter of culture medium was obtained
      after affinity purification with immobilized glutathione. The recombinant enzyme
      had full catalytic activity and kinetic parameters indistinguishable from those
      of the native enzyme purified from human erythrocytes.

PMID- 8550580
TI  - Characterization of the essential gene glmM encoding phosphoglucosamine mutase in
      Escherichia coli.
AB  - Two different approaches to identify the gene encoding the phosphoglucosamine
      mutase in Escherichia coli were used: (i) the purification to near homogeneity of
      this enzyme from a wild type strain and the determination of its N-terminal amino
      acid sequence; (ii) the search in data bases of an E. coli protein of unknown
      function showing sequence similarities with other hexosephosphate mutase
      activities. Both investigations revealed the same open reading frame named yhbF
      located within the leuU-dacB region at 69.5 min on the chromosome (Dallas, W. S.,
      Dev, I. K., and Ray, P. H. (1993) J. Bacteriol. 175, 7743-7744). The predicted
      445-residue protein with a calculated mass of 47.5 kDa contained in particular a
      short region GIVISASHNP with high similarity to the putative active site of
      hexosephosphate mutases. In vitro assays showed that the overexpression of this
      gene in E. coli cells led to a significant overproduction (from 15- to 50-fold)
      of phosphoglucosamine mutase activity. A hexose 1,6-diphosphate-dependent
      phosphorylation of the enzyme, which probably involves the serine residue at
      position 102, is apparently required for its catalytic action. As expected, the
      inactivation of this gene, which is essential for bacterial growth, led to the
      progressive depletion of the pools of precursors located downstream from
      glucosamine 1-phosphate in the pathway for peptidoglycan synthesis. This was
      followed by various alterations of cell shape and finally cells were lysed when
      their peptidoglycan content decreased to a critical value corresponding to about
      60% of its normal level. The gene for this enzyme, which is essential for
      peptidoglycan and lipopolysaccharide biosyntheses, has been designated glmM.

PMID- 8550581
TI  - Conjugation of the 15-kDa interferon-induced ubiquitin homolog is distinct from
      that of ubiquitin.
AB  - The biological effect of type 1 interferons is proposed to arise in part from the
      conjugation of ubiquitin cross-reactive protein (UCRP), the ISG15 gene product,
      to intracellular target proteins in a process analogous to that of its sequence
      homolog ubiquitin, a highly conserved 8.6-kDa polypeptide whose ligation marks
      proteins for degradation via the 26 S proteasome. Inclusion of CoCl2 during the
      purification of recombinant UCRP blocks the proteolytic inactivation of the
      polypeptide occurring by cleavage of the carboxyl-terminal glycine dipeptide
      required for activation and subsequent ligation. Intact UCRP supports a low rate
      of ubiquitin-activating enzyme (E1)-dependent ATP:PPi exchange but fails to form
      a stoichiometric E1-UCRP thiol ester or undergo transfer to ubiquitin carrier
      protein (E2). The binding affinity of E1 for UCRP is significantly diminished
      relative to that of ubiquitin. These results suggest that UCRP conjugation
      proceeds through an enzyme pathway distinct from that of ubiquitin, at least with
      respect to the step of activation. This was confirmed for an in vitro conjugation
      assay in which 125I-UCRP could be ligated in an ATP-dependent reaction to
      proteins present within an A549 human lung carcinoma cell extract and could be
      competitively inhibited by excess unlabeled UCRP but not ubiquitin. Other results
      demonstrate that 125I-UCRP conjugation is significantly increased in cell
      extracts after 24 h of incubation in the presence of interferon-beta, consistent
      with the late induction of UCRP conjugating activity. Thus, interferon-responsive
      cells contain a pathway for UCRP ligation that is parallel but distinct from that
      of ubiquitin.

PMID- 8550582
TI  - Expression of the insulin receptor with a recombinant vaccinia virus. Biochemical
      evidence that the insulin receptor has intrinsic serine kinase activity.
AB  - We have previously reported the tight association of a serine kinase activity
      with the human insulin receptor (Lewis, R. E., Wu, G. P., MacDonald, R. G., and
      Czech, M. P. (1990) J. Biol. Chem. 265, 947-954). We tested the possibility that
      the associated serine kinase activity was intrinsic to the receptor catalytic
      domain. The ratio of phosphoserine to phosphotyrosine on insulin receptors
      phosphorylated in vitro was used as an index of the associated serine kinase
      activity. Phosphorylation and phosphoamino acid analysis of insulin proreceptors
      revealed associated serine kinase activity early in receptor synthesis. Insulin
      receptors were expressed in HeLa cells using a recombinant vaccinia virus. The
      ratio of phosphoserine to phosphotyrosine on insulin receptors expressed by the
      recombinant vaccinia virus was determined relative to endogenous insulin
      receptors in cells treated with alpha-amanitin to block host cell mRNA synthesis.
      alpha-Amanitin treatment had no effect on the ratio of phosphoserine to
      phosphotyrosine on insulin receptors expressed from the recombinant virus even
      though they were present in a 4000-fold excess above endogenous receptors. We
      conclude that the serine kinase activity associated with the insulin receptor is
      intrinsic to the receptor catalytic domain. Receptor-catalyzed
      autophosphorylation of serine may play an important role in modulating insulin
      receptor signaling.

PMID- 8550583
TI  - Regulation of inducible nitric oxide synthase expression by macrophage
      purinoreceptors and calcium.
AB  - Macrophage activation is central to the progression of multiple diseases via the
      release of inflammatory mediators such as cytokines and nitric oxide. Despite the
      recognized overlap in the regulatory mechanisms involved in mediator production,
      little formation exists regarding receptor-initiated signaling pathways that
      coordinately control multiple end points, such as tumor necrosis factor-alpha
      (TNF-alpha) and nitric oxide production. In this study, the expression of
      inducible nitric oxide synthase (iNOS) in macrophages is shown to be regulated by
      calcium and by a purinoreceptor signaling system. The P2Y purinoreceptor partial
      agonist, 2-methylthio-ATP (2-MeS-ATP), inhibits the expression of iNOS induced by
      lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma) in primary
      macrophages. Additionally, 2-MeS-ATP attenuates the expression of iNOS in
      macrophages isolated from CD-1 mice challenged with LPS, and it inhibits LPS
      induced TNF-alpha and interleukin-1 alpha (IL-1 alpha) release, thereby
      preventing endotoxic death. Thus, purinoreceptors and calcium are likely to be
      critical for macrophage activation and the production of inflammatory mediators
      stimulated by LPS.

PMID- 8550584
TI  - Novel plant Ca(2+)-binding protein expressed in response to abscisic acid and
      osmotic stress.
AB  - A cDNA corresponding to an mRNA which accumulates in germinating rice seeds in
      response to the phytohormone abscisic acid was isolated by differential
      hybridization. Northern blotting indicated that the mRNA also accumulates in
      vegetative tissues in response to treatment with abscisic acid and to osmotic
      stress. Sequencing identified a major open reading frame encoding a novel protein
      of 27.4 kDa. The identity of the open reading frame was confirmed by comparing
      the translation products of cellular, hybrid-selected, and in vitro transcribed
      RNAs and by immunoprecipitation. Western blotting of cellular extracts indicated
      that the protein is associated with microsomal or membrane fractions. Data base
      searches indicated that it contains a conserved Ca(2+)-binding, EF-hand motif and
      that related proteins are similarly expressed in Arabidopsis thaliana. A fusion
      protein purified from Escherichia coli containing the putative EF-hand region was
      shown to bind Ca2+ in blot binding assays. These data identify a novel gene
      family encoding proteins involved in the response of plants to abscisic acid and
      osmotic stress.

PMID- 8550585
TI  - Discordant signal transduction and growth inhibition of small cell lung
      carcinomas induced by expression of GTPase-deficient G alpha 16.
AB  - Small cell lung carcinoma (SCLC) accounts for 20-25% of primary lung cancers and
      is rapidly growing, widely metastatic, and rarely curable. Autocrine stimulation
      of multiple G protein-coupled neuropeptide receptor systems contributes to the
      transformed growth of SCLC. The ability of neuropeptide receptors to stimulate
      phospholipase C and mobilize intracellular Ca2+ indicates that Gq family members
      of heterotrimeric G proteins are a convergence point mediating autocrine
      signaling by multiple neuropeptides in SCLC. Expression of a GTPase-deficient,
      constitutive active form of an alpha q family member, alpha 16Q212L, in SCLC
      markedly inhibited growth of the cells in soft agar and tumor formation in nude
      mice. SCLC lines expressing alpha 16Q212L exhibited 2-4-fold elevated basal
      phospholipase C activity, but neuropeptide and hormone-regulated intracellular
      Ca2+ mobilization was nearly abolished. The data suggest that Ca2+ mobilization
      is an obligatory signal in neuropeptide-stimulated growth of SCLC. In addition,
      the proline-directed c-Jun NH2-terminal kinases/stress-activated protein kinases,
      which are members of the mitogen-activated protein kinase family, were stimulated
      approximately 2-fold in parental SCLC in response to exogenous neuropeptides and
      muscarinic agonists and were constitutively activated to the same degree in alpha
      16Q212L-expressing SCLC. Thus, alpha 16Q212L expression induced desensitizaton of
      neuropeptide-stimulated Ca2+ signaling and persistent activation of the c-Jun NH2
      terminal kinase/stress-activated protein kinase pathway. We propose that the
      induction of discordant signaling by selective perturbation of receptor-regulated
      effector systems leads to the inhibition of SCLC cell growth.

PMID- 8550586
TI  - A new phospholipase C delta 4 is induced at S-phase of the cell cycle and appears
      in the nucleus.
AB  - To discover a new phospholipase C (PLC) related to cell growth, we screened a
      cDNA library prepared from regenerating rat liver. A novel PLC (PLC delta 4)
      encoding a polypeptide of 770 amino acids with structural similarity to PLC delta
      type isozymes was isolated. PLC delta 4 mRNA is expressed more remarkably in
      regenerating liver than in normal resting liver. It is also distributed
      abundantly in tumor cells such as hepatoma and src-transformed cells.
      Furthermore, its expression can be induced markedly by serum treatment and
      reaches a maximum at 8 h. Western blot analysis and immunocytochemical staining
      showed that PLC delta 4 is dominantly present in nucleus. Nuclear PLC delta 4
      dramatically increases at the transition from G1- to S-phase, and the high
      content continues to the end of M-phase. PLC delta 4 almost disappears when cells
      re-enter the next G1-phase. On the other hand, the contents of PLC beta 1, PLC
      gamma 1, and PLC delta 1 do not change significantly during the cell cycle. These
      results suggest that PLC delta 4 is expressed in nucleus in response to mitogenic
      stimulation and plays important roles in cell growth as one of the early genes
      expressed during the transition from G1- to S-phase in the cell cycle.

PMID- 8550587
TI  - Potent peptide analogues of a G protein receptor-binding region obtained with a
      combinatorial library.
AB  - The C terminus of the G protein alpha subunit represents an important site of
      interaction between heterotrimeric G proteins and their cognate receptors. We
      have screened a combinatorial peptide library based on the C terminus of the
      alpha subunit of Gt (340-350) and have identified unique sequences that bind
      rhodopsin with high affinity. Six of these sequences, as both fusion proteins and
      synthetic peptides, were significantly more potent than the parent sequence in
      binding to and stabilization of metarhodopsin II. These sequences provide
      information about which residues are required for appropriate receptor
      interaction. We observed that in all the high affinity sequences, a positively
      charged residue at position 341 was changed to a neutral one. Thus, it appears
      that the receptor-G protein interaction was designed to be low affinity to ensure
      efficient catalysis of G protein activation. We also observed Cys-347 and Gly-348
      to be invariant, and hydrophobic residues were always located at positions 340,
      344, 349, and 350, demonstrating the critical nature of these residues. A
      composite of the structures of the high affinity sequences was modeled based upon
      the structure of rhodopsin-bound trNOESY NMR of this region of Gt alpha (Dratz,
      E. D., Fursteneau, J. E., Lambert, C. G., Thireault, D. L., Rarick, H., Schepers,
      T., Pakhlevaniants, S., and Hamm, H. E. (1993) Nature 363, 276-280) and provides
      insight into the complementary G protein-binding surface of the receptor.

PMID- 8550588
TI  - Site-directed mutagenesis of the cysteine residues in the Neurospora crassa
      plasma membrane H(+)-ATPase.
AB  - A high-yield yeast expression system for site-directed mutagenesis of the
      Neurospora crassa plasma membrane H(+)-ATPase has recently been reported
      (Mahanty, S. K., Rao, U. S., Nicholas, R. A., and Scarborough, G. A. (1994) J.
      Biol. Chem. 269, 17705-17712). Using this system, each of the eight cysteine
      residues in the ATPase was changed to a serine or an alanine residue, producing
      strains C148S and C148A, C376S and C376A, C409S and C409A, C472S and C472A, C532S
      and C532A, C545S and C545A, C840S and C840A, and C869S and C869A, respectively.
      With the exception of C376S and C532S, all of the mutant ATPases are able to
      support the growth of yeast cells to different extents, indicating that they are
      functional. The C376S and C532S enzymes appear to be non-functional. After
      solubilization of the functional mutant ATPase molecules from isolated membranes
      with lysolecithin, all behaved similar to the native enzyme when subjected to
      glycerol density gradient centrifugation, indicating that they fold in a natural
      manner. The kinetic properties of these mutant enzymes were also similar to the
      native ATPase with the exception of C409A, which has a substantially higher Km.
      These results clearly indicate that none of the eight cysteine residues in the
      H(+)-ATPase molecule are essential for ATPase activity, but that Cys376, Cys409,
      and Cys532 may be in or near important sites. They also demonstrate that the
      previously described disulfide bridge between Cys148 and Cys840 or Cys869 plays
      no obvious role in the structure or function of this membrane transport enzyme.

PMID- 8550589
TI  - Conformational changes in oxyhemoglobin C (Glu beta 6-->Lys) detected by
      spectroscopic probing.
AB  - Hemoglobin C (Glu beta 6-->Lys) shares with hemoglobin S (Glu beta 6-->Val) the
      site of mutation, but with different consequences: deoxyHbS forms polymers,
      whereas oxyHbC readily forms crystals. The molecular mechanism for this property
      of oxyHbC is unknown. Since no detailed oxyHbC crystal structural information
      exists, spectroscopic probing is used in this study to investigate possible
      solution-phase conformational changes in HbC compared with HbA. Intrinsic
      fluorescence combined with UV resonance Raman data demonstrate a weakening of the
      Trp beta 15-Ser beta 72 hydrogen bond that most likely leads to a displacement of
      the A helix away from the E helix.

PMID- 8550591
TI  - Detection of undegraded oligonucleotides in vivo by fluorescence resonance energy
      transfer. Nuclease activities in living sea urchin eggs.
AB  - A method was investigated for monitoring the integrity of oligonucleotides in
      solution and in cells using fluorescence resonance energy transfer between two
      different fluorochromes attached to a single oligonucleotide. Ten-mer
      oligodeoxyribonucleotides labeled with fluorescein at one end and with rhodamine
      X at the other end were used. The oligomer had a specific absorption spectrum
      with peaks at 497 and 586 nm, which corresponded to fluorescein and rhodamine X,
      respectively. When excited at 494 nm, the oligomer had a specific fluorescence
      spectrum with peaks at 523 and 610 nm. The fluorescence intensity at 610 nm was 6
      8 times higher than that at 523 nm. After digestion of the oligomer with an
      endonuclease, the fluorescence at 523 nm increased more than 12-15-fold but its
      fluorescence peak at 610 nm almost completely disappeared. To examine effects in
      vivo, sea urchin eggs were injected with a solution of the oligomer and excited
      with blue light at 470-490 nm. Two fluorescent images, a green image at 520-560
      nm and a red image at above 580 nm, were obtained when a single egg was viewed
      under a fluorescence microscope. The ratio of the intensities of red to green
      fluorescence decreased in dependence on time after injection of the oligomer.
      These changes were not observed in eggs that had been injected with a solution of
      similarly double-labeled, phosphorothioate oligomer. These results indicated that
      unfertilized sea urchin eggs had nucleolytic activity. Analysis in vitro on
      supernatant of the egg homogenate indeed demonstrated the existence of nucleases.
      All together, our results indicate that the integrity of oligonucleotides can be
      estimated in living cells by monitoring the fluorescence resonance energy
      transfer of the double-labeled oligonucleotide.

PMID- 8550590
TI  - Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated
      proteolysis of I kappa B-alpha.
AB  - The NF-kappa B transcription factor induces rapid transcription of many genes in
      response to a variety of extracellular signals. NF-kappa B is readily activated
      from normally inhibited cytoplasmic stores by induced proteolytic degradation of
      I kappa B-alpha, a principal inhibitor of this transcription factor. Following
      the inhibitor's degradation, NF-kappa B is free to translocate to the nucleus and
      induce gene transcription. The I kappa B-alpha inhibitor is targeted for
      degradation by signal-induced phosphorylation of two closely spaced serines in
      its NH2 terminus (Ser32 and Ser36). Proteolytic degradation appears to be carried
      out by proteasomes which can recognize ubiquitinated intermediates of the I kappa
      B-alpha inhibitor. We provide evidence which supports a ubiquitin-mediated
      mechanism. Amino acid substitutions of two adjacent potential ubiquitination
      sites in the NH2 terminus of I kappa B-alpha (Lys21 and Lys22) almost completely
      block the rapid, signal-induced degradation of the mutant protein, while they do
      not interfere with induced phosphorylation. The mutant I kappa B-alpha also does
      not permit signal-induced activation of NF-kappa B bound to it. The data suggest
      that ubiquitination at either of the two adjacent lysines (21 and 22) is required
      for degradation following induced phosphorylation at nearby serines 32 and 36.
      Such dependence on ubiquitination of specific sites for protein degradation is
      unusual. This mechanism of degradation may also apply to I kappa B-beta, an
      inhibitor related to and functionally overlapping with I kappa B-alpha, as well
      as to cactus, an I kappa B homolog of Drosophila.

PMID- 8550592
TI  - Determinants of thyrotrope-specific thyrotropin beta promoter activation.
      Cooperation of Pit-1 with another factor.
AB  - Thyrotropin (TSH) beta is a subunit of TSH, the expression of which is limited to
      the thyrotrope cells of the anterior pituitary gland. We have utilized the
      thyrotrope-derived TtT-97 thyrotropic tumors to investigate tissue-specific
      expression of the TSH beta promoter. TSH beta promoter activity in thyrotropes is
      conferred by sequences between -270 and -80 of the 5'-flanking region. We have
      recently reported that the proximal region from -133 to -100 (P1) is required for
      promoter expression in thyrotropes. This region interacts with the pituitary
      specific transcription factor Pit-1. While Pit-1 appears necessary for TSH beta
      promoter activity in thyrotropes, this transcription factor is not alone
      sufficient for promoter activity in pituitary-derived cells. In this report, we
      have generated a series of promoter mutations in the P1 region to identify
      additional protein-DNA interactions and determine their functional significance.
      We have found that Pit-1 interacts with the distal portion of the P1 region, and
      a second protein interacts with the proximal segment of this region. Each protein
      is able to independently interact with the TSH beta promoter, but neither alone
      can maintain promoter activity. Both proteins appear to be necessary for full
      promoter activity in thyrotropes. Southwestern analysis with the proximal segment
      of the P1 region (-117 to -88) reveals interaction with a 50-kDa protein.
      Interestingly, this protein is not found in the pituitary-derived GH3 cells and
      may represent a thyrotrope-specific transcription factor. Further
      characterization of this newly identified DNA-binding protein will further our
      understanding of the tissue-specific expression of the TSH beta gene.

PMID- 8550593
TI  - Differential effects of overexpressed glucokinase and hexokinase I in isolated
      islets. Evidence for functional segregation of the high and low Km enzymes.
AB  - Glucose-stimulated insulin secretion is believed to require metabolism of the
      sugar via a high Km pathway in which glucokinase (hexokinase IV) is rate
      limiting. In this study, we have used recombinant adenoviruses to overexpress the
      liver and islet isoforms of glucokinase as well as low Km hexokinase I in
      isolated rat islets of Langerhans. Glucose phosphorylating activity increased by
      up to 20-fold in extracts from islets treated with adenoviruses containing the
      cDNAs encoding either tissue isoform of glucokinase, but such cells exhibited no
      increase in 2- or 5-[3H]glucose usage, lactate production, glycogen content, or
      glucose oxidation. Furthermore, glucokinase overexpression enhanced insulin
      secretion in response to stimulatory glucose or glucose plus arginine by only 36
      53% relative to control islets. In contrast to the minimal effects of
      overexpressed glucokinases, overexpression of hexokinase I caused a 2.5-4-fold
      enhancement in all metabolic parameters except glycogen content when measured at
      a basal glucose concentration (3 mM). Based on measurement of glucose
      phosphorylation in intact cells, overexpressed glucokinase is clearly active in a
      non-islet cell line (CV-1) but not within islet cells. That this result cannot be
      ascribed to the levels of glucokinase regulatory protein in islets is shown by
      direct measurement of its activity and mRNA. These data provide evidence for
      functional partitioning of glucokinase and hexokinase and suggest that
      overexpressed glucokinase must interact with factors found in limiting
      concentration in the islet cell in order to become activated and engage in
      productive metabolic signaling.

PMID- 8550594
TI  - Developmental pattern of expression and genomic organization of the calponin-h1
      gene. A contractile smooth muscle cell marker.
AB  - Calponin-h1 is a 34-kDa myofibrillar thin filament, actin-binding protein that is
      expressed exclusively in smooth muscle cells (SMCs) in adult animals. To examine
      the molecular mechanisms that regulate SMC-specific gene expression, we have
      examined the temporal, spatial, and cell cycle-regulated patterns of expression
      of calponin-h1 gene expression and isolated and structurally characterized the
      murine calponin-h1 gene. Calponin-h1 mRNA is expressed exclusively in SMC
      containing tissues in adult animals. During murine embryonic development,
      calponin-h1 gene expression is (i) detectable in E9.5 embryos in the dorsal
      aorta, cardiac outflow tract, and tubular heart, (ii) sequentially up-regulated
      in SMC-containing tissues, and (iii) down-regulated to non-detectable levels in
      the heart during late fetal development. In addition, the gene is expressed in
      resting rat aortic SMCs, but its expression is rapidly down-regulated when growth
      arrested cells reenter phase G1 of the cell cycle and proliferate. Calponin-h1 is
      encoded by a 10.7-kilobase single copy gene composed of seven exons, which is
      part of a multigene family. Transient transfection analyses demonstrated that 1.5
      kilobases of calponin-h1 5'-flanking sequence is sufficient to program high level
      transcription of a luciferase reporter gene in cultured primary rat aortic SMCs
      and the smooth muscle cell line, A7r5. Taken together, these data suggest that
      the calponin-h1 gene will serve as an excellent model system with which to
      examine the molecular mechanisms that regulate SMC lineage specification,
      differentiation, and phenotypic modulation.

PMID- 8550595
TI  - Modulation of superoxide-dependent oxidation and hydroxylation reactions by
      nitric oxide.
AB  - The rapid and spontaneous interaction between superoxide (O2-.) and nitric oxide
      (NO) to yield the potent oxidants peroxynitrite (ONOO-) and peroxynitrous acid
      (ONOOH), has been suggested to represent an important pathway by which tissue may
      be injured during inflammation. Although several groups of investigators have
      demonstrated substantial oxidizing and cytotoxic activities of chemically
      synthesized ONOO-, there has been little information available quantifying the
      interaction between O2-. and NO in the absence or the presence of redox-active
      iron. Using the hypoxanthine (HX)/xanthine oxidase system to generate various
      fluxes of O2-. and H2O2 and the spontaneous decomposition of the spermine/NO
      adduct to produce various fluxes of NO, we found that in the absence of redox
      active iron, the simultaneous production of equimolar fluxes of O2-. and NO
      increased the oxidation of dihydrorhodamine (DHR) from normally undetectable
      levels to approximately 15 microM, suggesting the formation of a potent oxidant.
      Superoxide dismutase, but not catalase, inhibited this oxidative reaction,
      suggesting that O2-. and not hydrogen peroxide (H2O2) interacts with NO to
      generate a potent oxidizing agent. Excess production of either radical virtually
      eliminated the oxidation of DHR. In the presence of 5 microM Fe+3-EDTA to insure
      optimum O2-.-driven Fenton chemistry, NO enhanced modestly HX/xanthine oxidase
      induced oxidation of DHR. As expected, both superoxide dismutase and catalase
      inhibited this Fe-catalyzed oxidation reaction. Excess NO production with respect
      to O2-. flux produced only modest inhibition (33%) of DHR oxidation. In a
      separate series of studies, we found that equimolar fluxes of O2-. and NO in the
      absence of iron only modestly enhanced hydroxylation of benzoic acid from
      undetectable levels to 0.6 microM 2-hydroxybenzoate. In the presence of 5 microM
      Fe+3-EDTA, HX/xanthine oxidase-mediated hydroxylation of benzoic acid increased
      dramatically from undetectable levels to 4.5 microM of the hydroxylated product.
      Superoxide dismutase and catalase were both effective at inhibiting this classic
      O2-.-driven Fenton reaction. Interestingly, NO inhibited this iron-catalyzed
      hydroxylation reaction in a concentration-dependent manner such that fluxes of NO
      approximating those of O2-. and H2O2 virtually abolished the hydroxylation of
      benzoic acid. We conclude that in the absence of iron, equimolar fluxes of NO and
      O2-. interact to yield potent oxidants such as ONOO-/ONOOH, which oxidize organic
      compounds. Excess production of either radical remarkably inhibits these
      oxidative reactions. In the presence of low molecular weight redox-active iron
      complexes, NO may enhance or inhibit O2-.-dependent oxidation and hydroxylation
      reactions depending upon their relative fluxes.

PMID- 8550596
TI  - Antagonistic regulation of tight junction dynamics by glucocorticoids and
      transforming growth factor-beta in mouse mammary epithelial cells.
AB  - The synthetic glucocorticoid, dexamethasone, stimulated the transepithelial
      electrical resistance and suppressed the DNA synthesis of 31EG4 nontransformed
      mouse mammary epithelial cells. The addition of transforming growth factor-beta 1
      (TGF-beta) to mammary cells simultaneously with or up to 24 h after dexamethasone
      treatment prevented the steroid induction of transepithelial electrical
      resistance and stimulated the incorporation of [3H]thymidine. However, the TGF
      beta inhibition of tight junction formation did not require de novo DNA
      synthesis. Confocal microscopy revealed that the organized immunostaining pattern
      of the tight junction protein, ZO-1, and F-actin at the cell periphery was
      disrupted by TGF-beta, resulting in disorganized and diffuse staining patterns
      throughout the cell. Western blot analysis demonstrated that TGF-beta did not
      alter the protein levels of ZO-1. In contrast to cells not treated or pretreated
      with steroid for up to 24 h, TGF-beta had no effect on cells pretreated with
      dexamethasone for 48 h. Transfection of chimeric reporter genes containing
      promoters responsive to either glucocorticoid or TGF-beta demonstrated that the
      mutual antagonism of tight junction dynamics by dexamethasone and TGF-beta occurs
      in the presence of intact signaling pathways. Taken together, our results
      establish for the first time that glucocorticoids and TGF-beta can
      antagonistically regulate tight junction formation in a nontransformed mammary
      cell line.

PMID- 8550597
TI  - Mapping of effector binding sites of transducin alpha-subunit using G alpha t/G
      alpha i1 chimeras.
AB  - The G protein transducin has been an often-used model for biochemical,
      structural, and mechanistic studies of G protein function. Experimental studies
      have been limited, however, by the inability to express quantities of mutants in
      heterologous systems with ease. In this study we have made a series of G alpha
      t/G alpha i1 chimeras differing at as few as 11 positions from native G alpha t.
      Ten chimeras are properly folded, contain GDP, can assume an A1F4(-)-induced
      activated conformation, and interact with beta gamma t and light-activated
      rhodopsin. They differ dramatically in their affinity for GDP, from Gi-like
      (initial rates 225 mumol/mol s) to Gt-like (initial rates 4.9 mumol/mol s). We
      have used these chimeras to define contact sites on G alpha t with the effector
      enzyme cGMP phosphodiesterase. G alpha t GTP but not G alpha t GDP activates it
      by removing the phosphodiesterase (PDE) gamma inhibitory subunit. In solution, G
      alpha t GTP interacts with PDE gamma (Kd 12 nM), while G alpha t GDP binds PDE
      gamma more weakly (Kd 0.88 microM). The interaction of G alpha i GDP with PDE
      gamma is undetectable, but G alpha i GDP-A1F4- interacts weakly with PDE gamma
      (Kd 2.4 microM). Using defined G alpha t/G alpha i chimeras, we have individuated
      the regions on G alpha t most important for interaction with PDE gamma in the
      basal and activated states. The G alpha t sequence encompassing alpha helix 3 and
      the alpha 3/beta 5 loop contributes most binding energy to interaction with PDE
      gamma. Another composite P gamma interaction site is the conserved switch,
      through which the GTP-bound G alpha t as well as G alpha i1 interact with P
      gamma. Competition studies between PDE gamma and truncated regions of PDE gamma
      provide evidence for the point-to-point interactions between the two proteins.
      The amino-terminal 1-45 segment containing the central polycationic region binds
      to G alpha t's alpha 3 helix and alpha 3/beta 5 loop, while the COOH-terminal
      region of P gamma, 63-87, binds in concert to the conserved switch regions. The
      first interaction provides specific interaction with both the GDP- and GTP
      liganded G alpha t, while the second one is conserved between G alpha t and G
      alpha i1 and dependent on the activated conformation.

PMID- 8550598
TI  - Cataractogenesis in transgenic mice containing the HIV-1 protease linked to the
      lens alpha A-crystallin promoter.
AB  - Several lines of transgenic mice were generated with either active or inactive
      forms of the human immunodeficiency virus type 1 (HIV-1) protease gene under the
      control of the mouse lens alpha A-crystallin promoter. Mice bearing the inactive
      protease coding sequence displayed no gross abnormalities in the lens, while mice
      with the active protease developed time-dependent bilateral cataracts. One line,
      TG61, developed cataracts in utero while the second line, TG72, developed
      cataracts postnatally. TG61 mice, homozygous for the transgene, developed severe
      microphthalmia and were significantly smaller than the control mice at postnatal
      day 30. two-dimensional-polyacrylamide gel electrophoresis analysis of the
      protein profiles of TG72 and TG61 lenses revealed extensive modifications in the
      lens crystallins. Proteolysis in the homozygous TG72 mouse lenses began at
      postnatal day 20 with the disappearance or partial loss of beta B1-, beta B3-,
      and beta A3-crystallins and the appearance of crystallin fragments. Protein
      leakage and the gradual breakdown of cytoskeletal elements also occurred. In
      contrast, the opacification of the homozygous TG61 lenses appeared to have been
      influenced by differentiation and developmental processes. It appears that HIV-1
      protease expression activates other proteases, and these enzymes, in concert with
      HIV-1 protease, are responsible for the protein modifications that eventually
      result in the opacification of the lens.

PMID- 8550599
TI  - The yeast Pan2 protein is required for poly(A)-binding protein-stimulated poly(A)
      nuclease activity.
AB  - The removal of the mRNA poly(A) tail in the yeast Saccharomyces cerevisiae is
      stimulated by the poly(A)-binding protein (Pab1p). A large scale purification of
      the Pab1p-stimulated poly(A) ribonuclease (PAN) identifies a 76-kDa and two 135
      Da polypeptides as candidate enzyme subunits. Antibodies against the Pan1p
      protein, which is the minor 135-kDa protein in the preparation, can immunodeplete
      Pan1p but not PAN activity. The protein sequence of the major 135-kDa protein,
      Pan2p, reveals a novel protein that was also found in the previously reported PAN
      purification (Sachs, A. B., and Deardorff, J. A. (1992) Cell 70, 961-973).
      Deletion of the non-essential PAN2 gene results in an increase of the average
      length of mRNA poly(A) tails in vivo, and a loss of Pab1p-stimulated PAN activity
      in crude extracts. These data confirm that Pan2p and not Pan1p is required for
      PAN activity, and they suggest that ribonucleases other than the Pab1p-stimulated
      PAN are capable of shortening poly(A) tails in vivo.

PMID- 8550600
TI  - Pasteurella multocida toxin, a potent intracellularly acting mitogen, induces
      p125FAK and paxillin tyrosine phosphorylation, actin stress fiber formation, and
      focal contact assembly in Swiss 3T3 cells.
AB  - Treatment of Swiss 3T3 cells with recombinant Pasteurella multocida toxin (rPMT),
      a potent intracellularly acting mitogen, stimulated tyrosine phosphorylation of
      multiple substrates including bands of M(r) 110,000-130,000 and M(r) 70,000
      80,000. Tyrosine phosphorylation induced by rPMT occurred after a pronounced lag
      period (1 h) and was blocked by either lysosomotrophic agents or incubation at 22
      degrees C. Focal adhesion kinase (p125FAK) and paxillin are prominent substrates
      for rPMT-stimulated tyrosine phosphorylation. Tyrosine phosphorylation by rPMT
      could be dissociated from both protein kinase C activation and the mobilization
      of calcium from intracellular stores. rPMT stimulated striking actin stress fiber
      formation and focal adhesion assembly in Swiss 3T3 cells. Cytochalasin D, which
      disrupts the actin cytoskeleton, completely inhibited rPMT-induced tyrosine
      phosphorylation. In addition, tyrosine phosphorylation of p125FAK and paxillin in
      response to rPMT was completely abolished when cells were subsequently treated
      with platelet-derived growth factor at a concentration (30 ng/ml) that disrupted
      the actin cytoskeleton. Our results demonstrate for the first time that rPMT, a
      bacterial toxin, induces tyrosine phosphorylation of p125FAK and paxillin and
      promotes actin stress fiber formation and focal adhesion assembly in Swiss 3T3
      cells.

PMID- 8550601
TI  - Cloning and membrane topology of a P type ATPase from Helicobacter pylori.
AB  - Southern blot screening of a genomic Helicobacter pylori library was employed to
      find a P type ATPase using a mixture of 16 DNA oligonucleotides coding for the
      DKTGT(I/L)T consensus sequence specific for the phosphorylation site of this
      family of ATPases. A positive clone, pRH439, was isolated and sequenced. The
      inserted 3.4-kb H. pylori DNA contained an intact open reading frame encoding a
      protein of 686 amino acids carrying the consensus sites for phosphorylation and
      ATP binding. The amino acid sequence exhibits a 25-30% identity with bacterial
      Cd2+ and Cu2+ ATPases. Genomic Southern blot analysis showed that this ATPase was
      present in all H. pylori strains examined, whereas it was not detectable in
      Campylobacter jejuni and other bacteria. The membrane topology of this ATPase was
      investigated using in vitro transcription/translation of fusion vectors to find
      signal anchor and/or stop transfer sequences. Eight regions of the H. pylori
      ATPase acted as signal anchor and/or stop transfer sequences and were ordered
      pairwise along the polypeptide chain placing the N and C-terminal amino acids in
      the cytoplasm. These transmembrane segments are contained between positions 73
      and 92 (H1), 98 and 125 (H2), 128 and 148 (H3), 149 and 176 (H4), 309 and 327
      (H5), 337 and 371 (H6), 637 and 658 (H7), and 659 and 685 (H8). The membrane
      domain of the ATPase, therefore, consists of at least four pairs of transmembrane
      segments with the phosphorylation site and ATP binding domain located in the
      large cytoplasmic loop between H6 and H7. The cytoplasmic domain contains several
      histidines and cysteines, perhaps indicative of divalent cation binding sites.
      There are several charged amino acids (3 Lys, 2 Glu, 2 Asp), predicted to be in
      the membrane domain mainly in H2, H3, and H4 and a Cys-Pro-Cys putative metal ion
      site in H6. The extracytoplasmic domain also has several charged amino acids (5
      Glu, 1 Asp, 1 Lys, 1 Arg). It is likely that this novel protein is a heavy metal
      cation transporting ATPase and belongs to a family of P type ATPases containing
      eight transmembrane segments.

PMID- 8550602
TI  - Biochemical characterization and molecular cloning of cardiac triadin.
AB  - Triadin is an intrinsic membrane protein first identified in the skeletal muscle
      junctional sarcoplasmic reticulum and is considered to play an important role in
      excitation-contraction coupling. Using polyclonal antibodies to skeletal muscle
      triadin, we have identified and characterized three isoforms in rabbit cardiac
      muscle. The cDNAs encoding these three isoforms of triadin have been isolated by
      reverse transcription-polymerase chain reaction and cDNA library screening. The
      deduced amino acid sequences show that these proteins are identical in their N
      terminal sequences, whereas the C-terminal sequences are distinct from each other
      and from that of skeletal muscle triadin. Based upon both the amino acid
      sequences and biochemical analysis, all three triadin isoforms share similar
      membrane topology with skeletal muscle triadin. Immunofluorescence staining of
      rabbit cardiac muscle with antibodies purified from the homologous region of
      triadin shows that cardiac triadin is primarily confined to the I-band region of
      cardiac myocytes, where the junctional and corbular sarcoplasmic reticulum is
      located. Furthermore, we demonstrate that the conserved region of the luminal
      domain of triadin is able to bind both the ryanodine receptor and calsequestrin
      in cardiac muscle. These results suggest that triadin colocalizes with and binds
      to the ryanodine receptor and calsequestrin and carries out a function in the
      lumen of the junctional sarcoplasmic reticulum that is important for both
      skeletal and cardiac muscle excitation-contraction coupling.

PMID- 8550603
TI  - SNAP prevents Mg(2+)-ATP-induced release of N-ethylmaleimide-sensitive factor
      from the Golgi apparatus in digitonin-permeabilized PC12 cells.
AB  - The N-ethylmaleimide-sensitive factor (NSF), which is involved in the multisteps
      of protein transport, is released from Golgi membranes on in vitro incubation
      with Mg(2+)-ATP. However, several lines of evidence suggest that NSF is
      associated with membranes in spite of the presence of Mg2+ and ATP in vivo. We
      have used digitonin-permeabilized PC12 cells to investigate the mechanism
      underlying the association of NSF with membranes. In PC12 cells, immunoreactivity
      for NSF was observed in the nuclear membranes, the Golgi apparatus, and neuronal
      growth cones, where synaptic vesicles are concentrated. NSF associated with the
      Golgi apparatus was released on incubation with Mg(2+)-ATP, whereas NSF in the
      nuclear membranes and neuronal growth cones was not released on the same
      treatment. The addition of cytosol blocked the Mg(2+)-ATP-induced release of NSF
      from the Golgi apparatus. Chromatographic analyses revealed that the factor(s)
      that prevents NSF release from the Golgi apparatus was eluted at the same
      position as the soluble NSF attachment proteins (SNAPs). Purified His6-tagged
      alpha-SNAP exhibited such activity. His6-tagged alpha-SNAP also prevented the
      Mg(2+)-ATP-induced release of NSF from isolated Golgi membranes.

PMID- 8550604
TI  - Biochemical characterization of the human cyclin-dependent protein kinase
      activating kinase. Identification of p35 as a novel regulatory subunit.
AB  - The activation of cyclin-dependent protein kinases (Cdks) is dependent upon site
      specific phosphorylation and dephosphorylation reactions, as well as positive and
      negative regulatory subunits. The human Cdk-activating protein kinase (Cak1) is
      itself a Cdc2-related cyclin-dependent protein kinase that associates with cyclin
      H. The present study utilized specific anti-Cak1 antibodies and immunoaffinity
      chromatography to identify additional Cak1-associated proteins and potential
      target substrates. Immunoprecipitation of metabolically labeled human
      osteosarcoma cells revealed a number of Cak1-associated proteins, including p95,
      p37 (cyclin H), and a 35-kDa protein that was further characterized herein.
      Microsequence analysis obtained after limited proteolysis revealed peptide
      fragments that are similar, but not identical to, human and yeast cyclins, thus
      identifying p35 as a cyclin-like regulatory subunit. The greatest sequence
      similarity of human p35 is with Mcs2, a yeast cyclin that is essential for cell
      cycle progression. Immunoaffinity chromatography performed under nondenaturing
      conditions afforded the isolation of enzymatically active Cak1 from cell lysates,
      enabling studies of kinase autophosphorylation and comparative substrate
      utilization. Immunoaffinity-purified Cak1 phosphorylated monomeric Cdc2 and Cdk2,
      but not Cdk4; the phosphorylation of both Cdc2 and Cdk2 were increased in the
      presence of recombinant cyclin A. These studies indicate that the Cak1 catalytic
      subunit, like Cdc2 and Cdk2, associates with multiple regulatory partners and
      suggests that subunit composition may be an important determinant of this
      multifunctional enzyme.

PMID- 8550605
TI  - Inositol 1,4,5-trisphosphate receptor is located to the inner nuclear membrane
      vindicating regulation of nuclear calcium signaling by inositol 1,4,5
      trisphosphate. Discrete distribution of inositol phosphate receptors to inner and
      outer nuclear membranes.
AB  - Transient rise in nuclear calcium concentration is implicated in the regulation
      of events controlling gene expression. Mechanism by which calcium is transported
      to the nucleus is vehemently debated. Inositol 1,4,5-trisphosphate (InsP3) and
      inositol-1,3,4,5-tetrakisphosphate (InsP4) receptors have been located to the
      nucleus and their role in nuclear calcium signaling has been proposed. Outer
      nuclear membrane was separated from the inner membrane. The two membrane
      preparations were, as best as possible, devoid of cross contamination as attested
      by marker enzyme activity, Western blotting with antilamin antibody, and electron
      microscopy. InsP4 receptor and Ca(2+)-ATPase were located to the outer nuclear
      membrane. InsP3 receptor was located to the inner nuclear membrane. ATP or InsP4
      induced nuclear calcium uptake. External free calcium concentration, in the
      medium bathing the nuclei, determined the choice for ATP or InsP4-mediated
      calcium transport. We present a mechanistic model for nuclear calcium transport.
      According to this model, calcium can reach the nucleus envelope either by the
      action of ATP or InsP4. However, the calcium release from the nucleus envelope to
      the nucleoplasm is mediated by InsP3 through the activation of InsP3 receptor,
      which is located to the inner nuclear membrane. The action of InsP3 in this
      process was instantaneous and transient and was sensitive to heparin.

PMID- 8550606
TI  - Secretory granule content proteins and the luminal domains of granule membrane
      proteins aggregate in vitro at mildly acidic pH.
AB  - A major unresolved issue in the field of secretory granule biogenesis is the
      extent to which the aggregation of granule content proteins is responsible for
      the sorting of regulated from constitutively secreted proteins. The aggregation
      process is postulated to take place in the trans-Golgi network and immature
      secretory granules as the proteins encounter mildly acidic pH and high calcium
      concentrations. We have developed in vitro assays that reconstitute the
      precipitation out of solution of secretory granule content proteins of anterior
      pituitary gland and adrenal medulla. In the assays, all of the major granule
      content polypeptides form a precipitate as the pH is titrated below 6.5, and this
      precipitate can be recovered in the pellet fraction after centrifugation.
      Addition of calcium is required for the aggregation of chromaffin granule
      content. In contrast to the proteins secreted by the regulated pathway, the
      constitutively secreted proteins IgG, albumin, and angiotensinogen, when added to
      the assays, remain predominantly in the supernatant. Among the individual
      proteins tested, prolactin is found to aggregate homophilically under these
      conditions and can drive the co-aggregation of other proteins, such as the
      chromogranins. Soluble forms of granule membrane proteins, including dopamine
      beta-hydroxylase and peptidyl glycine alpha-amidating enzyme also co-aggregated
      with granule content proteins. The results are consistent with the idea that
      spontaneous aggregation of proteins occurring under ionic conditions similar to
      those at the sites of granule formation is a property restricted to those
      proteins packaged in secretory granules. In addition, the association of luminal
      domains of membrane proteins with content proteins in vitro raises the
      possibility that analogous interactions between membrane-bound and content
      proteins also occur during granule formation in intact cells.

PMID- 8550607
TI  - Molecular cloning of F4/80, a murine macrophage-restricted cell surface
      glycoprotein with homology to the G-protein-linked transmembrane 7 hormone
      receptor family.
AB  - F4/80 is a monoclonal antibody that recognizes a murine macrophage-restricted
      cell surface glycoprotein and has been extensively used to characterize
      macrophage populations in a wide range of immunological studies. Apart from the
      tightly regulated pattern of expression of the F4/80 antigen, little is known
      about its possible role in macrophage differentiation and function. We have
      sought to characterize the molecule at the molecular level, through the isolation
      of cDNA clones, and now describe the sequence of the F4/80 protein. The primary
      amino acid sequence demonstrates homology to two protein superfamilies. The NH2
      terminal region consists of seven epidermal growth factor-like domains, separated
      by approximately 300 amino acids from a COOH-terminal region that shows homology
      to members of the seven transmembrane-spanning family of hormone receptors. The
      potential role of these distinct domains is discussed with respect to the
      possible function of the F4/80 molecule.

PMID- 8550608
TI  - Structure and promoter analysis of the gene encoding the human melanoma
      inhibiting protein MIA.
AB  - We have recently described the isolation of a novel protein, MIA, which is
      secreted from malignant melanoma cells and elicits growth inhibition on melanoma
      cells in vitro (Blesch, A., Bosserhoff, A. K., Apfel, R., Behl, C., Hessdorfer,
      B., Schmitt, A., Jachimczak, P., Lottspeich, F., Schlingensiepen, H., Buettner,
      R., and Bogdahn, U. (1994) Cancer Res. 54, 5695-5701). Here, we report the
      structure of the human MIA gene locus, describe its expression pattern in
      melanocytic tumors in vivo, and provide an initial characterization of the MIA
      promoter. The MIA gene is encoded by four exons, and the mRNA initiation site was
      identified 70 base pairs upstream from the translation start codon. MIA mRNA
      expression in vivo correlated with progressive malignancy of melanocytic lesions
      and was inducible in other cells by phorbol esters. To investigate mechanisms
      mediating this melanoma-associated expression pattern, we analyzed the promoter
      activity of the 1.3-kilobase genomic sequences located 5'-upstream of the MIA
      gene. The MIA promoter conferred high levels of gene activation specifically in
      human and murine melanoma cells, and its activity was further enhanced by
      treatment with phorbol esters. Site-directed mutation of an NF-kB site within the
      MIA promoter did reduce the basal promoter activity in melanoma cells but did not
      change significantly enhancement by phorbol esters.

PMID- 8550609
TI  - Functional importance of the amino terminus of Gq alpha.
AB  - Gq alpha is palmitoylated at residues Cys9 and Cys10. Removal of palmitate from
      purified Gq alpha with palmitoylthioesterase in vitro failed to alter
      interactions of Gq alpha with phospholipase C-beta 1, the G protein beta gamma
      subunit complex, or m1 muscarinic cholinergic receptors. Mutants C9A, C10A,
      C9A/C10A, C9S/C10S, and truncated Gq alpha (removal of residues 1-6) were
      synthesized in Sf9 cells and purified. Loss of both Cys residues or truncation
      prevented palmitoylation of Gq alpha. However, truncated Gq alpha and the single
      Cys mutants activated phospholipase C-beta 1 normally, while the double Cys
      mutants were poor activators. Loss of both Cys residues impaired but did not
      abolish interaction of Gq alpha with m1 receptors. These Cys residues are thus
      important regardless of their state of palmitoylation. When expressed in HEK-293
      or Sf9 cells, all of the proteins studied associated entirely or predominantly
      with membranes, although a minor fraction of nonpalmitoylated Gq alpha proteins
      accumulated in the cytosol of HEK-293 cells. When subjected to TX-114 phase
      partitioning, a significant fraction of all of the proteins, including those with
      no palmitate, was found in the detergent-rich phase. Removal of residues 1-34 of
      Gq alpha caused a loss of surface hydrophobicity as evidenced by complete
      partitioning into the aqueous phase. The Cys residues at the amino terminus of Gq
      alpha are thus important for its interactions with effector and receptor, and the
      amino terminus conveys a hydrophobic character to the protein distinct from that
      contributed by palmitate.

PMID- 8550610
TI  - Transforming growth factor-beta 1 inhibits nucleosomal fragmentation in human
      keratinocytes following loss of adhesion.
AB  - We have investigated the role of transforming growth factor-beta 1 (TGF-beta 1)
      in suspension-induced programmed cell death of cultured human keratinocytes.
      Suspension of keratinocytes in semisolid medium induces TGF-beta 1 mRNA levels
      and synthesis of bioactive TGF-beta 1 protein. Concomitant with the suspension
      induced increase in secreted TGF-beta 1 levels, steady state mRNA levels for c
      myc are decreased. Both exogenously added and endogenously produced TGF-beta 1
      attenuate suspension-induced nucleosomal fragmentation in keratinocytes. We
      propose that TGF-beta 1 may function to protect keratinocytes from DNA
      fragmentation following loss of cell-substratum and/or cell-cell contact. Taken
      together, our findings suggest that loss of cell-substratum and/or cell-cell
      adhesion is an important component of an apoptotic signal transduction cascade
      regulated by TGF-beta 1 in normal human stratified squamous epithelia.

PMID- 8550611
TI  - Platelet-derived growth factor stimulates protein kinase A through a mitogen
      activated protein kinase-dependent pathway in human arterial smooth muscle cells.
AB  - The abilities of platelet-derived growth factor (PDGF) and insulin-like growth
      factor (IGF-I) to regulate cAMP metabolism and mitogen-activated protein kinase
      (MAP kinase) activity were compared in human arterial smooth muscle cells (hSMC).
      PDGF-BB stimulated cAMP accumulation up to 150-fold in a concentration-dependent
      manner (EC50 approximately 0.7 nM). The peak of cAMP formation and cAMP-dependent
      protein kinase (PKA) activity occurred approximately 5 min after the addition of
      PDGF and rapidly declined thereafter. Incubating cells with PDGF and 3-isobutyl-1
      methylxanthine (IBMX, a phosphodiesterase inhibitor) enhanced the accumulation of
      cAMP and PKA activity by an additional 2.5-3-fold, whereas IBMX alone was
      essentially without effect. The PDGF-stimulated increase in cAMP was prevented by
      addition of the cyclooxygenase inhibitor indomethacin, consistent with release of
      prostaglandins stimulating cAMP. PDGF, but not IGF-I, stimulated MAPK activity,
      cytosolic phospholipase A2 (cPLA2) phosphorylation, and cAMP synthesis which
      indicated a key role for MAP kinase in the activation of cPLA2. Further, PDGF
      stimulated the rapid release of arachidonic acid and synthesis of prostaglandin
      E2 (PGE2) which could be inhibited by a cPLA2 inhibitor (AACOCF3). Calcium
      mobilization was required for PDGF-induced arachidonic acid release and PGE2
      synthesis but not for MAPK activation, whereas PKC was required for PGE2-mediated
      activation of PKA. In summary, these results demonstrated that PDGF increases
      cAMP formation and PKA activity through a MAP kinase-mediated activation of
      cPLA2, arachidonic acid release, and PGE2 synthesis in human arterial smooth
      muscle cells.

PMID- 8550612
TI  - Transcriptional analysis of the 5'-noncoding region of the human involucrin gene.
AB  - Human involucrin whose gene transcription is directed by a 2456-nucleotide (nt)
      5'-noncoding region is a structural component of the epithelial cornified layer.
      Transient transfection assays demonstrated that this region is transcriptionally
      active in multiplying keratinocytes and is enhanced by 2 mM CaCl2 treatment.
      Calcium-independent transcriptional activity and the interaction with the AP-1
      transcriptional factor was located on the proximal part (nt -159 to -1) of the 5'
      noncoding region. However, CaCl2 responsiveness was mapped to a distal 1185-nt
      fragment (nt -2456 to -1272). Moreover, this fragment potentiated the Herpes
      simplex thymidine kinase promoter in normal keratinocytes and is responsive to
      calcium treatment in a cell type-specific manner. Interestingly, the absence of a
      491-nt fragment located between the two enhancer domains (nt -651 to -160)
      resulted in transcriptional activation in multiplying keratinocytes. This
      fragment interacts with AP-1 and the YY1 transcriptional silencer. It is
      concluded that human involucrin 5'-noncoding region contains at least three
      regulatory domains, a distal CaCl2-responsive enhancer, a putative
      transcriptional silencer (that interacts with AP-1 and YY1), and a proximal
      enhancer/promoter (that interacts with AP-1). Thus, this study demonstrates the
      presence of particular transcriptional factors can potentially regulate the human
      involucrin expression.

PMID- 8550613
TI  - Two hydrophobic subunits are essential for the heme b ligation and functional
      assembly of complex II (succinate-ubiquinone oxidoreductase) from Escherichia
      coli.
AB  - Complex II (succinate-ubiquinone oxidoreductase) from Escherichia coli is
      composed of four nonidentical subunits encoded by the sdhCDAB operon. Gene
      products of sdhC and sdhD are small hydrophobic subunits that anchor the
      hydrophilic catalytic subunits (flavoprotein and iron-sulfur protein) to the
      cytoplasmic membrane and are believed to be the components of cytochrome b556 in
      E. coli complex II. In the present study, to elucidate the role of two
      hydrophobic subunits in the heme b ligation and functional assembly of complex
      II, plasmids carrying portions of the sdh gene were constructed and introduced
      into E. coli MK3, which lacks succinate dehydrogenase and fumarate reductase
      activities. The expression of polypeptides with molecular masses of about 19 and
      17 kDa was observed when sdhC and sdhD were introduced into MK3, respectively,
      indicating that sdhC encodes the large subunit (cybL) and sdhD the small subunit
      (cybS) of cytochrome b556. An increase in cytochrome b content was found in the
      membrane when sdhD was introduced, while the cytochrome b content did not change
      when sdhC was introduced. However, the cytochrome b expressed by the plasmid
      carrying sdhD differed from cytochrome b556 in its CO reactivity and red shift of
      the alpha absorption peak to 557.5 nm at 77 K. Neither hydrophobic subunit was
      able to bind the catalytic portion to the membrane, and only succinate
      dehydrogenase activity, not succinate-ubiquinone oxidoreductase activity, was
      found in the cytoplasmic fractions of the cells. In contrast, significantly
      higher amounts of cytochrome b556 were expressed in the membrane when sdhC and
      sdhD genes were both present, and the catalytic portion was found to be localized
      in the membrane with succinate-ubiquitnone oxidoreductase and succinate oxidase
      activities. These results strongly suggest that both hydrophobic subunits are
      required for heme insertion into cytochrome b556 and are essential for the
      functional assembly of E. coli complex II in the membrane. Accumulation of the
      catalytic portion in the cytoplasm was found when sdhCDAB was introduced into a
      heme synthesis mutant, suggesting the importance of heme in the assembly of E.
      coli complex II.

PMID- 8550614
TI  - Intersubunit surfaces in G protein alpha beta gamma heterotrimers. Analysis by
      cross-linking and mutagenesis of beta gamma.
AB  - Heterotrimeric guanine nucleotide binding proteins (G proteins) are made up of
      alpha, beta, and gamma subunits, the last two forming a very tight complex.
      Stimulation of cell surface receptors promotes dissociation of alpha from the
      beta gamma dimer, which, in turn, allows both components to interact with
      intracellular enzymes or ion channels and modulate their activity. At present,
      little is known about the conformation of the beta gamma dimer or about the areas
      of beta gamma that interact with alpha. Direct information on the orientation of
      protein surfaces can be obtained from the analysis of chemically cross-linked
      products. Previous work in this laboratory showed that 1,6-bismaleimidohexane,
      which reacts with cysteine residues, specifically cross-links alpha to beta and
      beta to gamma (Yi, F., Denker, B. M., and Neer, E. J. (1991) J. Biol. Chem. 266,
      3900-3906). To identify the residues in beta and gamma involved in cross-linking
      to each other or to alpha, we have mutated the cysteines in beta 1, gamma 2, and
      gamma 3 and analyzed the mutated proteins by in vitro translation in a rabbit
      reticulocyte lysate. All the mutants were able to form beta gamma dimers that
      could interact with the alpha subunit. We found that 1,6-bismaleimidohexane can
      cross-link beta 1 to gamma 3 but not to gamma 2. The cross-link goes from Cys25
      in beta 1 to Cys30 in gamma 3. This cysteine is absent from any of the other
      known gamma isoforms and therefore confers a distinctive property to gamma 3. The
      beta subunit in the beta 1 gamma 2 dimer can be cross-linked to an unidentified
      protein in the rabbit reticulocyte lysate, generating a product slightly larger
      than cross-linked beta 1 gamma 3. The beta subunit can also be cross-linked to
      alpha, giving rise to two products on SDS-polyacrylamide gel electrophoresis,
      both of which were previously shown to be formed by cross-linking beta to Cys215
      in alpha o (Thomas, T. C., Schmidt, C. J., and Neer, E. J. (1993) Proc. Natl.
      Acad. Sci. U.S.A. 90, 10295-10299). Mutation of Cys204 in beta 1 abolished one of
      these two products, whereas mutation of Cys271 abolished the other. Because both
      alpha-beta cross-linked products are formed in approximately equal amounts,
      Cys204 and Cys271 in beta are equally accessible from Cys215 in alpha o. Our
      findings begin to define intersubunit surfaces, and they pose structural
      constraints upon any model of the beta gamma dimer.

PMID- 8550615
TI  - Characterization of three components of human adenovirus proteinase activity in
      vitro.
AB  - Human adenovirus contains a virion-associated proteinase activity essential for
      the development of infectious virus. Maximal proteinase activity in vitro had
      been shown to require three viral components: the L3 23-kDa protein, an 11-amino
      acid cofactor (pVIc), and the viral DNA. Here, we present a quantitative
      purification procedure for a recombinant L3 23-kDa protein (recombinant
      endoproteinase (rEP)) expressed in Escherichia coli and the procedure that led to
      the purification and identification of pVIc as a cofactor. The cofactors
      stimulate proteinase activity not by decreasing Km, which changes by no more than
      2-fold, but by increasing kcat. rEP alone had a small amount of activity, the
      kcat of which increased 355-fold with pVIc and 6072-fold with adenovirus serotype
      2 (Ad2) DNA as well. Curves of Vmax of rEP.pVIc complexes with the substrate (Leu
      Arg-Gly-NH)2-rhodamine as a function of pH in the absence and presence of Ad2 DNA
      indicate that the pKa values of amino acids that affect catalysis are quite
      different from those that affect catalysis by the cysteine proteinase papain. The
      pKa values in the absence of Ad2 DNA are 5.2, 6.4, 6.9, 7.5, and 9.4, and those
      in its presence are 5.2, 6.5, 7.4, and 8.8.

PMID- 8550616
TI  - Atrial natriuretic peptide induces the expression of MKP-1, a mitogen-activated
      protein kinase phosphatase, in glomerular mesangial cells.
AB  - Atrial natriuretic peptide (ANP) has been shown to inhibit the proliferation of
      various types of cells including glomerular mesangial cells. The activation of
      mitogen-activated protein kinase (MAPK) is one of the main signal transduction
      systems leading to cell proliferation. MAPK is tightly regulated by the
      activating kinase, MEK, and specific phosphatase MKP-1. Constitutive expression
      of MKP-1 has been shown to inhibit cell proliferation by suppressing MAPK
      activity. In order to understand the mechanism of the anti-proliferative effect
      of ANP, we examined whether ANP could inhibit MAPK by inducing MKP-1 in cultured
      rat glomerular mesangial cells. ANP increased the expression of MKP-1 mRNA in a
      dose-dependent (10 nM maximum) and time-dependent, with a peak stimulation at 30
      min, manner. Receptor for ANP is a transmembrane guanylyl cyclase. Activation of
      guanylyl cyclase of ANP receptor by ligand plays an essential role in ANP signal
      transduction. 8-Bromo-cGMP, a cell permeable analogue of cyclic GMP, and sodium
      nitroprusside, an activator of soluble guanylyl cyclase, could mimic the effects
      of ANP and were able to induce the expression of MKP-1 in a similar time course
      as ANP. The protein expression of MKP-1 was maximally stimulated by ANP at 120
      min. Treatment of the cells with ANP for 120 min resulted in an inhibition of
      phorbol ester-induced activation of MAPK, while the activation of MEK was not
      affected by ANP. These results indicate that ANP might inhibit the proliferation
      of mesangial cells by inactivating MAPK through the induction of MKP-1.

PMID- 8550617
TI  - Overexpression of myotonic dystrophy kinase in BC3H1 cells induces the skeletal
      muscle phenotype.
AB  - Myotonic muscular dystrophy is an autosomal dominant defect that produces muscle
      wasting, myotonia, and cardiac conduction abnormalities. The myotonic dystrophy
      locus codes for a putative serine-threonine protein kinase of unknown function.
      We report that overexpression of human myotonic dystrophy protein kinase induces
      the expression of skeletal muscle-specific genes in undifferentiated BC3H1 muscle
      cells. BC3H1 clones expressing myotonic dystrophy kinase appear equivalent to
      differentiated cells with respect to expression of myogenin, retinoblastoma tumor
      supressor gene, M creatine kinase, beta-tropomyosin, and vimentin. In addition,
      differential display analysis demonstrates that the pattern of gene expression
      exhibited by myotonic dystrophy kinase-expressing cells is essentially identical
      to that of differentiated BC3H1 muscle cells. These observations suggest that
      myotonic dystrophy kinase may function in the myogenic pathway.

PMID- 8550618
TI  - Protein kinase C-mediated phosphorylation of the myristoylated alanine-rich C
      kinase substrate protects it from specific proteolytic cleavage.
AB  - The myristoylated alanine-rich C kinase substrate (MARCKS) is a major cellular
      substrate of protein kinase C. Its concentration in cells is important for the
      normal development of the central nervous system, and perhaps other physiological
      processes. We found that MARCKS concentrations in cells were regulated in part by
      a specific proteolytic cleavage; this resulted in two fragments, each
      representing about half of the intact protein, that co-existed with MARCKS in
      cells and tissues. These fragments were present in significant concentrations in
      quiescent fibroblasts; they disappeared, and the amount of intact MARCKS
      increased, within 15 s of activation of protein kinase C by serum. In vitro
      experiments demonstrated that phosphorylated MARCKS was a poor substrate for a
      protease activity present in cell extracts, whereas dephosphorylated MARCKS was a
      good substrate. Both the protease activity and the specific MARCKS cleavage
      products were essentially absent in brain, but present in many other cells and
      tissues. The protease activity, which had the characteristics of a cysteine
      protease, cleaved MARCKS between Asn147 and Glu148 of the bovine sequence, three
      amino acids to the amino-terminal side of the MARCKS phosphorylation site domain.
      These studies demonstrate that MARCKS is subjected to specific cleavage by a
      cellular protease, in a manner dependent on the phosphorylation state of the
      substrate. This represents a novel means of regulating cellular MARCKS
      concentrations; these data also raise the interesting possibility that MARCKS is
      involved in regulating the activity of this novel cellular protease.

PMID- 8550619
TI  - Human placental leucine aminopeptidase/oxytocinase. A new member of type II
      membrane-spanning zinc metallopeptidase family.
AB  - The serum level of placental leucine aminopeptidase (P-LAP) increases during
      pregnancy. P-LAP degrades several peptide hormones such as oxytocin and
      vasopresin, suggesting a role in maintaining homeostasis during pregnancy. In the
      study reported here, we have isolated a cDNA clone with 4084 base pairs encoding
      P-LAP from a human placental cDNA library. The amino acid sequence deduced from
      the cDNA contained all of the sequences of the peptide fragments obtained by
      digestion of the purified protein with trypsin. The predicted P-LAP contains the
      HEXXH consensus sequence of zinc metallopeptidases, indicating that the enzyme
      belongs to this family, which includes aminopeptidase N and aminopeptidase A. The
      deduced sequence also contains a hydrophobic region near the N terminus,
      suggesting that the enzyme is a type II integral membrane protein. Northern blot
      analysis revealed that P-LAP was expressed in several tissues, some of which
      expressed two forms of mRNAs. These results suggest that the enzyme is
      synthesized as an integral membrane protein and is released into blood under some
      physiological conditions.

PMID- 8550620
TI  - p120cbl is a cytosolic adapter protein that associates with phosphoinositide 3
      kinase in response to epidermal growth factor in PC12 and other cells.
AB  - Although epidermal growth factor (EGF) activates phosphoinositide (PI) 3-kinase
      activity in a number of types of cells or cell lines, in most cases that we have
      investigated the p85 regulatory subunit of PI 3-kinase does not appear to bind
      directly to the EGF receptor. Previously we demonstrated that EGF-dependent
      activation of PI 3-kinase activity in A431 cells is accompanied by the binding of
      p85 to ErbB3, an EGF receptor homologue. However, this mechanism did not explain
      the large activation of PI 3-kinase activity that was found in PC12 and A549
      cells, which possess little or no ErbB3. Here we provide evidence that the
      p120cbl proto-oncoprotein is an intracellular adapter protein that associates
      with PI 3-kinase and thus is involved in the EGF-dependent activation of this
      enzyme in these two cell lines. Using an anti-p120cbl antibody, we
      immunoprecipitated the EGF receptor from PC12 cells and PI 3-kinase activity from
      PC12 and A549 cells in an EGF-dependent fashion. Treatment of PC12 cells with
      nerve growth factor or insulin stimulated large increases in PI 3-kinase activity
      that was immunoprecipitated using anti-Tyr(P) antibody but not using anti-p120cbl
      antibody. In EGF-treated PC12 cells, the tyrosine phosphorylation of p120cbl
      displayed similar kinetics to the activation of PI 3-kinase as measured by both
      in vivo lipid production and lipid kinase assays conducted using anti-p120cbl and
      anti-Tyr(P) immunoprecipitates. The use of glutathione S-transferase fusion
      proteins of various domains of p85 demonstrated that p120cbl associated with both
      the SH2 and SH3 domains of p85. p120cbl was also present in A431 cells and offers
      an additional pathway by which EGF can activate PI 3-kinase in these cells.

PMID- 8550621
TI  - Expression and characterization of recombinant caveolin. Purification by
      polyhistidine tagging and cholesterol-dependent incorporation into defined lipid
      membranes.
AB  - Caveolin, a 22-24-kDa integral membrane protein, is a principal component of
      caveolar membranes in vivo. Caveolin has been proposed to function as a
      scaffolding protein to organize and concentrate signaling molecules within
      caveolae. Because of its unusual membrane topology, both the N- and C-terminal
      domains of caveolin remain entirely cytoplasmic and are not subject to luminal
      modifications that are accessible to other integral membrane proteins. Under
      certain conditions, caveolin also exists in a soluble form as a cytosolic protein
      in vivo. These properties make caveolin an attractive candidate for recombinant
      expression in Escherichia coli. Here, we successfully expressed recombinant full
      length caveolin in E.coli. A polyhistidine tag was placed at its extreme C
      terminus for purification by Ni(2+)-nitrilotriacetic acid affinity
      chromatography. Specific antibody probes demonstrated that recombinant caveolin
      contained a complete N and C terminus. Recombinant caveolin remained soluble in
      solutions containing the detergent octyl glucoside and formed high molecular mass
      oligomers like endogenous caveolin. By electron microscopy, recombinant caveolin
      homo-oligomers appeared as individual spherical particles that were
      indistinguishable from endogenous caveolin homo-oligomers visualized by the same
      technique. As recombinant caveolin behaved as expected for endogenous caveolin,
      this provides an indication that recombinant caveolin can be used to dissect the
      structural and functional interaction of caveolin with other protein and lipid
      molecules in vitro. Recombinant caveolin was efficiently incorporated into lipid
      membranes as assessed by floatation in sucrose density gradients. This allowed us
      to use defined lipid components to assess the possible requirements for insertion
      of caveolin into membranes. Using a purified synthetic form of
      phosphatidylcholine (1,2-dioleoylphosphorylcholine), we observed that
      incorporation of caveolin into membranes was cholesterol-dependent; the addition
      of cholesterol dramatically increased the incorporation of caveolin into these
      phosphatidylcholine-based membranes by approximately 25-30-fold. This fits well
      with in vivo studies demonstrating that cholesterol plays an essential role in
      maintaining the structure and function of caveolae. Further functional analysis
      of these reconstituted caveolin-containing membranes showed that they were
      capable of recruiting a soluble recombinant form of G(i)2 alpha. This is in
      accordance with previous studies demonstrating that caveolin specifically
      interacts directly with multiple G protein alpha-subunits. Thus, recombinant
      caveolin incorporated into defined lipid membranes provides an experimental
      system in which the structure, function, and biogenesis of caveolin-rich membrane
      domains can be dissected in vitro.

PMID- 8550622
TI  - G alpha i RNA antisense expression demonstrates the exclusive coupling of peptide
      YY receptors to G(i)2 proteins in renal proximal tubule cells.
AB  - A clone PKSV-PCT Cl.10 referred to as Cl.10 was selected from the PKSV-PCT renal
      proximal tubule cell line which expressed peptide YY (PYY) receptors (Voisin, T.,
      Bens, M., Cluzeaud, F., Vandewalle, A., and Laburthe, M. (1993) J. Biol. Chem.
      268, 20547-20554). In order to identify G(i) protein(s) coupled to PYY receptors,
      antisense G alpha i protein RNAs were expressed in Cl.10 cells by transfecting
      the pcDNA3 vector into which were inserted 39 bases of the 5'-noncoding region of
      G alpha i2 or G alpha i3 used as specific antisense templates. A Cl.10/alpha i2
      clone was selected which displayed a drastic decrease (> 90%) of the expression
      of G alpha i2 without changes of G alpha i3, G alpha s, and G beta subunits (G
      alpha i1 is not present in Cl.10 cells) as evidenced by Western blots. When
      compared to untransfected cells, this clone exhibited: (i) an increase in the
      dissociation constant of PYY receptors (5.3 versus 0.6 nM) identical to that
      observed in pertussis toxin-treated untransfected cells; (ii) an absence of
      inhibition of 125I-PYY binding by guanosine 5'-O-(thiotriphosphate) (GTP gamma
      S); and (iii) the failure of PYY to inhibit cAMP levels and to stimulate [methyl
      3H]thymidine incorporation into DNA. A clone was also selected which exhibited a
      specific decrease (> 80%) of G alpha i3 as compared to untransfected cells. The
      sensitivity to GTP gamma S and the dissociation constant of PYY receptors as well
      as PYY-mediated inhibition of cAMP were identical to those observed in
      untransfected cells. These findings support an exclusive coupling of PYY
      receptors to G alpha i2.

PMID- 8550623
TI  - Genetic probing of the first and second transmembrane helices of the plasma
      membrane H(+)-ATPase from Saccharomyces cerevisiae.
AB  - Structural features of the putative helical hairpin region comprising
      transmembrane segments 1 (TM1) and 2 (TM2) of the yeast plasma membrane H(+)
      ATPase were probed by site-directed mutagenesis. The importance of phenylalanine
      residues Phe-116, Phe-119, Phe-120, Phe-126, Phe-144, Phe-159, and Phe-163 was
      explored by alanine replacement mutagenesis. It was found that substitutions at
      all positions, except Phe-120 and Phe-144, produced viable enzymes, although a
      range of cellular growth phenotypes were observed like hygromycin B resistance
      and low pH sensitivity, which are linked to in vivo action of the H(+)-ATPase.
      Lethal positions Phe-120 and Phe-144, could be replaced with tryptophan to
      produce viable enzyme, although the F144W mutant was highly perturbed. ATP
      hydrolysis measurements showed that Km was not significantly altered for most
      mutant enzymes, whereas Vmax was moderately reduced with two mutants, F144W and
      F163A, showing less than 50% of the normal activity. Double Phe-->Ala mutations
      in TM1 and TM2 were constructed to examine whether such substitutions would
      result in a higher degree of enzyme destabilization. Mutant F116A/F119A was
      viable and gave a normal phenotype, while F159A/F163A was not viable. Other
      double mutants, F116A/F159A and F119AF/159A, which are predicted to lie
      juxtaposed on TM1 and TM2, produced non-functional enzymes. However, a viable
      F119V/F159A mutant was isolated and showed hygromycin B resistance. These results
      suggest that double mutations eliminating 2 phenylalanine residues strongly
      destabilize the enzyme. A putative proline kink at Gly-122/Pro-123 in TM1 is not
      essential for enzyme action since these residues could be variously substituted
      (G122A or G122N; P123A, P123G, or P123F) producing viable enzymes with moderate
      effects on in vitro ATP hydrolysis or proton transport. However, several
      substitutions produced prominent growth phenotypes, suggesting that local
      perturbations were occurring. The location of Pro-123 is important because Gly
      122 and Pro-123 could not be exchanged. In addition, a double Pro-Pro created by
      a G122P mutation was lethal, suggesting that maintenance of an alpha-helical
      structure is important. Other mutations in the hairpin, including modification of
      a buried charged residue, E129A, were not critical for enzyme action. These data
      are consistent with the view that the helical hairpin comprising TM1 and TM2 has
      important structural determinants that contribute to its overall stability and
      flexibility.

PMID- 8550624
TI  - Regulation of interaction of ras p21 with RalGDS and Raf-1 by cyclic AMP
      dependent protein kinase.
AB  - RalGDS is a GDP/GTP exchange protein for ral p24, a member of small GTP-binding
      protein superfamily. We have recently shown that RalGDS interacts directly with
      the GTP-bound active form of ras p21 through the effector loop of ras p21 in
      vitro, in insect cells and in the yeast two-hybrid system. These results suggest
      that RalGDS functions as an effector protein of ras p21. Here, we report that
      RalGDS interacts with ras p21 in mammalian cells in response to an extracellular
      signal. Epidermal growth factor (EGF) induced the interaction of c-ras p21 and
      RalGDS in COS cells expressing both proteins, but not in the cells expressing
      RalGDS and c-ras p21T35A, which is an effector loop mutant of ras p21. We also
      found that cyclic AMP-dependent protein kinase (protein kinase A) regulated the
      selectivity of ras p21-binding to either RalGDS or Raf-1. Protein kinase A
      phosphorylated RalGDS as well as (1-149)Raf (amino acid residues 1-149). Although
      the phosphorylated (1-149)Raf had a lower affinity for ras p21 than the
      unphosphorylated (1-149)Raf, both the phosphorylated and unphosphorylated RalGDS
      had the similar affinities for ras p21. The phosphorylation of RalGDS did not
      affect its activity to stimulate the GDP/GTP exchange of ral p24. Pretreatment of
      COS cells with forskolin further stimulated the interaction of ras p21 and RalGDS
      induced by EGF under the conditions that EGF-dependent Raf-1 activity was
      inhibited. These results indicate that ras p21 distinguishes between RalGDS and
      Raf-1 by their phosphorylation by protein kinase A.

PMID- 8550625
TI  - Mechanisms identified in the transcriptional control of epithelial gene
      expression.
AB  - Epithelium-specific gene expression is fundamental in both embryogenesis and the
      maintenance of adult tissues, and impairment of epithelial characteristics
      contributes to diseases such as cancer. We have here analyzed the 5'-region of
      the epithelial (E-) cadherin gene in order to understand mechanisms of epithelium
      specific transcription and loss of expression during epithelial-mesenchymal
      transitions. The regulatory region of the mouse epithelial cadherin gene is
      composed of a promoter (from position -94 to the transcription start site) and a
      150-base pair enhancer located in the first intron. The 5'-promoter consists of
      positive regulatory elements (a CCAAT-box and two AP-2 binding sites in a GC-rich
      region) and the palindromic element E-Pal that activates and represses
      transcription in epithelial and mesenchymal cells, respectively. The enhancer of
      the first intron stimulates the activity of heterologous promoters exclusively in
      epithelial cells. This epithelium-specific enhancer consists of three elements (E
      I to E III; E II and E III bind AP-2) that are necessary and sufficient for
      activity. We thus propose two regulatory mechanisms by which epithelial
      specificity of epithelial cadherin expression is determined: suppression of
      promoter activity in mesenchymal cells by E-Pal and enhancement of activity in
      epithelial cells by both E-Pal and the epithelium-specific enhancer.

PMID- 8550626
TI  - Different mechanisms for Ca2+ dissociation from complexes of calmodulin with
      nitric oxide synthase or myosin light chain kinase.
AB  - We have determined the stoichiometry and rate constants for the dissociation of
      Ca2+ ion from calmodulin (CaM) complexes with rabbit skeletal muscle myosin light
      chain kinase (skMLCK), rat brain nitric oxide synthase (nNOS) or with the
      respective peptides (skPEP and nPEP) representing the CaM-binding domains in
      these enzymes. Ca2+ dissociation kinetics determined by stopped-flow fluorescence
      using the Ca2+ chelator quin-2 MF are as follows. 1) Two sites in the CaM-nNOS
      and CaM-nPEP complexes have a rate constant of 1 s-1. 2) The remaining two sites
      have a rate constant of 18 s-1 for CaM-nPEP and > 1000 s-1 for CaM-nNOS. 3) Three
      sites have a rate constant of 1.6 s-1 for CaM-skMLCK and 0.15 s-1 for CaM-skPEP.
      4) The remaining site has a rate constant of 2 s-1 for CaM-skPEP and > 1000 s-1
      for CaM-skMLCK. Comparison of these rate constants with those determined for
      complexes between the peptides and tryptic fragments representing the C- or N
      terminal lobes of CaM indicate a mechanism for Ca2+ dissociation from CaM-nNOS of
      2C slow + 2N fast and from CaM-skMLCK of (2C + 1N) slow + 1N fast. Ca2+ removal
      inactivates CaM-nNOS and CaM-skMLCK activities with respective rate constants of
      > 10 s-1 and 1 s-1. CaM-nNOS inactivation is fit by a model in which rapid Ca2+
      dissociation from the N-terminal lobe of CaM is coupled to enzyme inactivation
      and slower Ca2+ dissociation from the C-terminal lobe is coupled to dissociation
      of the CaM-nNOS complex. CaM-skMLCK inactivation is fit by a model in which the
      three slowly dissociating Ca(2+)-binding sites are coupled to both dissociation
      of the complex and enzyme inactivation.

PMID- 8550627
TI  - Biochemical characterization of symmetric GroEL-GroES complexes. Evidence for a
      role in protein folding.
AB  - When chaperonins GroEL and GroES are incubated under functional conditions in the
      presence of ATP (5 mM) and K+ (150 mM), GroEL-GroES complexes appear in the
      incubation mixture, that are either asymmetric (1:1 GroEL:GroES oligomer ratio)
      or symmetric (1:2 GroEL:GroES oligomer ratio). The percentage of symmetric
      complexes present is directly related to the [ATP]/[ADP] ratio and to the K+
      concentration. Kinetic analysis shows that there is a cycle of formation and
      disappearance of symmetric complexes. A correlation between the presence of
      symmetric complexes in the incubation mixture and its rhodanese folding activity
      suggests some active role of these complexes in the protein folding process.
      Accordingly, under functional conditions, symmetric complexes are found to
      contain denatured rhodanese. These data suggest that binding of substrate inside
      the GroEL cavity takes place before the symmetric complex is formed.

PMID- 8550628
TI  - Nuclear signaling by endothelin-1 requires Src protein-tyrosine kinases.
AB  - In response to changes in vascular homeostasis, endothelial cells secrete
      endothelin-1 (ET-1), which in turn regulates gene expression and phenotype in
      underlying vascular cells. We characterized a nuclear signaling cascade in which
      Src protein-tyrosine kinases link the ET-1 receptor to induction of c-fos
      transcription. A dominant negative SrcK- kinase mutant blocked ET-1-stimulated c
      fos transcription. Expression of the COOH-terminal Src kinase (Csk), which
      represses Src kinases, also blocked induction of c-fos transcription by ET-1.
      Activation of the c-fos promoter by ET-1 required both the CArG DNA sequence of
      the c-fos serum response element and the Ca2+/cAMP response element. In contrast,
      Src-induced c-fos transcription required only the CArG cis-element, demonstrating
      a divergence in signals regulating c-fos transcription. Thus, Src kinases
      contribute to a nuclear signaling cascade linking an ET-1 receptor to the CArG
      element of the c-fos serum response element. A Src-based pathway might play a
      more general role to propagate ET-1 nuclear signals that regulate cell growth and
      development. In addition, these results point to a widening role for nonreceptor
      protein-tyrosine kinases in propagating signals from G protein-coupled receptors.

PMID- 8550630
TI  - Assembly and cell surface expression of heteromeric and homomeric gamma
      aminobutyric acid type A receptors.
AB  - The ability of differing subunit combinations of gamma-aminobutyric acid type A
      (GABAA) receptors produced from murine alpha 1, beta 2, and gamma 2L subunits to
      form functional cell surface receptors was analyzed in both A293 cells and
      Xenopus oocytes using a combination of molecular, electrophysiological,
      biochemical, and morphological approaches. The results revealed that GABAA
      receptor assembly occurred within the endoplasmic reticulum and involved the
      interaction with the chaperone molecules immunoglobulin heavy chain binding
      protein and calnexin. Despite all three subunits possessing the ability to
      oligomerize with each other, only alpha 1 beta 2 and alpha 1 beta 2 gamma 2L
      subunit combinations could produce functional surface expression in a process
      that was not dependent on N-linked glycosylation. Single subunits and the alpha 1
      gamma 2L and beta 2 gamma 2L combinations were retained within the endoplasmic
      reticulum. These results suggest that receptor assembly occurs by defined
      pathways, which may serve to limit the diversity of GABAA receptors that exist on
      the surface of neurons.

PMID- 8550629
TI  - The Rac target NADPH oxidase p67phox interacts preferentially with Rac2 rather
      than Rac1.
AB  - NADPH oxidase is a plasma membrane enzyme of phagocytes generating superoxide
      anions which serve as bactericidal agents. Activation of this multimolecular
      enzyme minimally requires assembly at the membrane with flavocytochrome b558 of
      cytosolic components p47phox, p67phox, and Rac proteins. Rac1 and Rac2 are 92%
      homologous cytosolic small GTPase proteins. Both Rac1 and Rac2 have been
      implicated with NADPH oxidase activation in vitro; however, Rac2 is largely
      predominant in human phagocytes. Here, using the yeast two-hybrid system, we
      provide data demonstrating in vivo interactions between human p47phox, p67phox,
      and Rac proteins. Rac proteins interact with p67phox in a GTP-dependent manner,
      but do not interact with p47phox. Moreover, Rac effector site mutants, which are
      known to be inactive in NADPH oxidase, lose their interaction with p67phox;
      Rac2L61 mutant, which has an increased NADPH oxidase affinity, shows an increased
      affinity for p67phox. Finally, we observe that p67phox interacts 6-fold better
      with Rac2 than with Rac1. We also show a strong intracellular interaction between
      p47phox and p67phox. These results indicate that activated Rac can regulate NADPH
      oxidase by interacting with p67phox and that Rac2 is the main p67phox-interacting
      GTPase in human cells.

PMID- 8550631
TI  - Identification of an interferon-gamma receptor alpha chain sequence required for
      JAK-1 binding.
AB  - We have shown previously that a four-amino acid block residing at positions 266
      269 (LPKS) in the intracellular domain of the human interferon-gamma (IFN-gamma)
      receptor alpha chain is critical for IFN-gamma-dependent tyrosine kinase
      activation and biologic response induction. Herein we show that this sequence is
      required for the constitutive attachment of the tyrosine kinase JAK-1. Using a
      vaccinia expression system, a receptor alpha chain-specific monoclonal antibody
      coprecipitated JAK-1 from cells coexpressing JAK-1 and either (a) wild type IFN
      gamma receptor alpha chain, (b) a receptor alpha chain truncation mutant
      containing only the first 59 intracellular domain amino acids, or (c) a receptor
      mutant containing alanine substitutions for the functionally irrelevant residues
      272-275. In contrast, JAK-1 was not coprecipitated when coexpressed with a
      receptor alpha chain mutant containing alanine substitutions for the functionally
      critical residues 266-269 (LPKS). Mutagenesis of the LPKS sequence revealed that
      Pro-267 is the only residue obligatorily required for receptor function. In
      addition, Pro-267 is required for JAK-1 binding. These results thus identify a
      site in the IFN-gamma receptor alpha chain required for constitutive JAK-1
      association and establish that this association is critical for IFN-gamma signal
      transduction.

PMID- 8550632
TI  - Calreticulin interacts with newly synthesized human immunodeficiency virus type 1
      envelope glycoprotein, suggesting a chaperone function similar to that of
      calnexin.
AB  - The ubiquitous eukaryotic protein calreticulin has been detected in a wide
      variety of different cell types. Recently, calreticulin was found to bind in
      vitro to a number of proteins isolated from the endoplasmic reticulum. In
      addition, calreticulin has sequence similarities with the molecular chaperone
      calnexin. These data suggest that calreticulin might also act as a chaperone. We
      found that calreticulin associated transiently with a large number of newly
      synthesized cellular proteins. In cells expressing recombinant human
      immunodeficiency virus (HIV) envelope glycoprotein, gp160 bound transiently to
      calreticulin with a peak at 10 min after its synthesis. Binding of gp120 to
      calreticulin was not detected because proteolytic cleavage of gp160 occurs in the
      trans-Golgi. Nonglycosylated HIV envelope protein was not associated with
      calreticulin, suggesting a requirement for N-linked oligosaccharides on newly
      synthesized proteins as has been reported for calnexin. The in vivo binding
      kinetics of calnexin and calreticulin to gp160 were very similar. Sequential
      immunoprecipitations provided evidence for the existence of ternary complexes of
      gp160, calreticulin, and calnexin. The data suggested that most of the gp160
      associated with calreticulin was also bound to calnexin but that only a portion
      of the gp160 associated with calnexin was also bound to calreticulin.

PMID- 8550633
TI  - Sonoelastic determination of human skeletal muscle elasticity.
AB  - It is not currently practical to directly measure viscoelastic parameters in
      human muscles in situ. Methods used in vitro cannot readily be applied, and
      motion analysis provides only a gross estimate. We report on the application of a
      hybrid approach, sonoelastography, which uses ultrasound to measure the
      propagation of shear waves induced by externally applied vibrations. Because
      shear waves predominate in incompressible viscoelastic media at low frequencies,
      sonoelastic data should be comparable to those obtained using conventional means.
      We recorded vibration propagation speeds as a function of applied load in the
      quadriceps muscles of ten volunteers as they underwent a series of static
      contractions. Data collection during dynamic contractions, not possible with the
      current equipment, will be the subject of future experimentation. Although
      statistically significant correlations were not uniformly obtained above 60 Hz
      nor for propagation perpendicular to the muscle fibers, this is felt to have
      resulted from deviations from the applied plane wave model. Calculated values of
      Young's modulus for 30 Hz propagation parallel to the muscle fibers were 7 +/- 3,
      29 +/- 12 and 57 +/- 37 x 10(3) Nm-2 for applied loads of 0, 7.5 and 15 kg,
      respectively. The corresponding values at 60 Hz were 25 +/- 6, 75 +/- 61 and 127
      +/- 65. These values were statistically significant and linearly correlated with
      the applied load, as expected. Our data represent the first in situ human
      measurements of their kind. It is anticipated that sonoelastography will provide
      a useful adjunct to the study of human biomechanics.

PMID- 8550634
TI  - Tradeoffs between motion and stability in posterior substituting knee
      arthroplasty design.
AB  - The purpose of this study was to examine how changes in component geometry of
      posterior substituting knees affect tibiofemoral kinematics and prosthesis
      stability. Most posterior cruciate ligament substituting prostheses rely on an
      articulation between a femoral cam and tibial spine to provide anterior-posterior
      stability of the knee. Failure of this ligament substitution mechanism has
      resulted in knee dislocations with several different posterior substituting
      designs. A computer model of a generic posterior substituting prosthesis was
      altered to analyze the effects of five design parameters (tibial spine height,
      spine anterior-posterior position, femoral component posterior radius, and
      femoral cam anterior-posterior and distal-proximal position) on prosthesis
      stability, tibiofemoral kinematics, and maximum obtainable knee flexion.
      Prosthesis stability was characterized by a 'dislocation safety factor', defined
      as the vertical distance from the bottom of the femoral cam to the top of the
      tibial spine. Computer simulations revealed that posterior substituting knees are
      most likely to dislocate at maximum knee flexion. Prosthesis stability can be
      improved by increasing the tibial spine height and moving the femoral cam
      posteriorly. Our results suggest there is a tradeoff between maximum knee flexion
      and prosthesis stability. We found that relatively small gains in maximum knee
      flexion, made through design changes, may cause substantial decreases in
      prosthesis stability.

PMID- 8550635
TI  - Finite element stress analysis of left ventricular mechanics in the beating dog
      heart.
AB  - A three-dimensional finite element model was used to explore whether or not
      transmural distributions of end-diastolic and end-systolic fiber stress are
      uniform from the apex to the base of the canine left ventricular wall. An
      elastance model for active fiber stress was incorporated in an axisymmetric model
      that accurately represented the geometry and fiber angle distribution of the
      anterior free wall. The nonlinear constitutive equation for the resting
      myocardium was transversely isotropic with respect to the local fiber axis.
      Transmural distributions of end-diastolic fiber stress became increasingly
      nonuniform from midventricle toward the apex or the base. At a typical diastolic
      left ventricular pressure (1 kPa), the differences between largest and smallest
      fiber stresses were only 0.5 kPa near midventricle, compared with 4.6 kPa at the
      apex, and 3.3 kPa at the base. Transmural fiber stress differences at end-systole
      (14 kPa) were relatively small in regions from the base to the midventricle (13
      22 kPa), but were larger between midventricle and the apex (30-43 kPa). All six
      three-dimensional end-diastolic strain components were within or very close to
      one standard deviation of published measurements through the midanterior left
      ventricular free wall of the passive canine heart [Omens et al., Am. J. Physiol.
      261, H918-H928 (1991)]. End-systolic in-plane normal and shear strains also
      agreed closely with published experimental measurements in the beating dog heart
      [Waldman et al., Circ. Res. 63, 550-562 (1988)]. The results indicate that,
      unlike in the midventricle region that has been studied most fully, there may be
      significant regional nonhomogeneity of fiber stress in the normal left ventricle
      associated with regional variations in shape and fiber angle.

PMID- 8550636
TI  - The control of shoulder muscles during goal directed movements, an inverse
      dynamic analysis.
AB  - Fast goal directed arm movements in the sagittal plane were analyzed with a three
      dimensional shoulder model with 95 muscle elements. Dynamics of the muscle
      elements were described by a third-order nonlinear muscle model. Muscle forces
      and activation were estimated using the method of inverse muscular dynamics, an
      optimization scheme which uses only very limited computational power. Most model
      results were similar to the EMG but some differences between model results and
      EMG were found in muscles where the EMG activity was subject dependent. For the
      movement studied, the thoracoscapular muscles were shown to deliver about 40% of
      the energy required for the acceleration of the arm during anteflexion and about
      22% during retroflexion. Activity of thoracoscapular muscles was also required to
      ensure contact between the thorax and the scapula which is important for the
      mechanical stability of the shoulder. The rotator cuff muscles were found to
      deliver about 19% of the energy required for the acceleration of the arm during
      anteflexion and about 8% during retroflexion.

PMID- 8550637
TI  - The role of synovial fluid filtration by cartilage in lubrication of synovial
      joints--III. Squeeze-film lubrication: axial symmetry under low loading
      conditions.
AB  - A mixture model of synovial fluid filtration and synovial gel formation at normal
      approach of cartilage surfaces in the human synovial joints loaded by a
      compressive force has been recently presented in Parts I and II of this paper
      (Hlavacek, 1993, J. Biomechanics 26, 1145-1150; 1151-1160). In the model synovial
      fluid is taken as a mixture of two incompressible fluids (ideal and Newtonian
      viscous), while the biphasic model of Mow et al. (1980, J. Biomech. Engng 102, 73
      84) is used for cartilage. A system of partial differential equations for the
      normal approach of axially symmetric cartilage surfaces in the human hip joint
      obtained in Part II is solved numerically for low loads. A shallow pocket-type
      configuration of the synovial film is formed shortly after the load application
      at time t = 0. For constant loads the fluid film pressure profile follows very
      closely that in a dry frictionless contact. To this approximation and with the
      exception of a close vicinity of the squeeze-film edge the flux of the ideal
      fluid across the synovial fluid-cartilage interface varies quadratically with the
      radial distance r and decreases as t-1/2 with time. The ideal fluid is forced
      into cartilage at the central region and out of cartilage at the low-pressure
      periphery of the squeezed synovial film. The maximum gel-forming concentration
      (the 20-fold of the original value) of the hyaluronic acid-protein macromolecular
      complex of the synovial fluid is reached at the film centre first, then the gel
      film starts spreading quickly sideways. Later, the process slows down approaching
      the value r/2 1/2 where r is the radius of a dry frictionless contact. The final
      gel-film thickness decreases very slowly with the increasing r for 0 < or = r <
      r/2 1/2.

PMID- 8550638
TI  - The role of synovial fluid filtration by cartilage in lubrication of synovial
      joints--IV. Squeeze-film lubrication: the central film thickness for normal and
      inflammatory synovial fluids for axial symmetry under high loading conditions.
AB  - The axially symmetric problem of synovial film filtration and synovial gel
      formation at normal approach of cartilage surfaces in the human hip joint loaded
      by a compressive force has been solved numerically in Part III of this paper
      [Hlavacek and Novak, J. Biomechanics 28, 1193-1198 (1995)] for the Newtonian
      viscous phase of the biphasic synovial fluid and for low loads only. Because of a
      high non-linearity of the problem the method used there breaks down for higher
      loads. On anticipating that for a high step loading the fluid pressure in the
      central part of the squeezed synovial film is close to the pressure in a dry
      frictionless contact, the synovial film filtration at the film centre is governed
      by two ordinary differential equations that are easy to solve. The central gel
      film thickness thus obtained, i.e. the film thickness at the moment, when the
      filtered fluid turns into a stable gel is about 1 micron for the normal synovial
      fluid (with a non-Newtonian viscous phase of the synovial fluid) and changes very
      little if the geometric, material and loading parameters of the problem vary
      within the physiological range. The inflammatory case (with a more or less
      Newtonian viscous phase) yields values by one order lower at least. The results
      of stress analysis in the cartilage for this mixture model suggest the reason for
      vertical cracking at the free cartilage surface and horizontal splitting at the
      tide mark observed in osteoarthritic joints.

PMID- 8550639
TI  - Residual strain and local strain distributions in the rabbit atherosclerotic
      aorta.
AB  - Effect of atherosclerosis on the residual strain in the arterial wall was studied
      in the rabbit thoracic aorta. Atherosclerosis was induced by feeding a
      cholesterol diet or by combining denudation of aortic endothelial cells with the
      diet feeding. Diameter of each aorta in the physiological state was determined
      from a static pressure-diameter test. A ring specimen was obtained from the
      position where the diameter was measured. After the measurement of its no-load
      diameters, the ring was cut radially to measure the opening angle. Histological
      section was then obtained from the opened-up ring specimen. The section was
      divided into 32 subsections and local dimensions were measured for each
      subsection. Residual and in vivo strains referring to the opened-up configuration
      were calculated from the local dimensions and the diameters in the unloaded and
      physiological states. The opening angle significantly correlated with the area
      fraction of intimal hyperplasia until severe calcification occurred, while it had
      a negative correlation with the area fraction of calcified region. Histological
      observation of opened-up ring specimens indicated that the media adjacent to
      hyperplastic intima remained stretched, while that away from the intima relaxed.
      Analysis of local strains showed that, in the atherosclerotic aorta without
      calcification, higher residual strain (compressive), i.e., lower in vivo strain
      (tensile), appears in the thicker intima. These results suggest that: (a) intimal
      hyperplasia increases residual strain and thus reduces the in vivo strain exerted
      in the intima and (b) calcified tissue restrains the deformation of adjacent
      tissues. The intimal hyperplasia and the calcification may complicate strain
      fields in the atherosclerotic aorta.

PMID- 8550640
TI  - NLT and extrapolated DLT:3-D cinematography alternatives for enlarging the volume
      of calibration.
AB  - This study investigated the accuracy of the direct linear transformation (DLT)
      and non-linear transformation (NLT) methods of 3-D cinematography/videography. A
      comparison of standard DLT, extrapolated DLT, and NLT calibrations showed the
      standard (non-extrapolated) DLT to be the most accurate, especially when a large
      number of control points (40-60) were used. The NLT was more accurate than the
      extrapolated DLT when the level of extrapolation exceeded 100%. The results
      indicated that when possible one should use the DLT with a control object,
      sufficiently large as to encompass the entire activity being studied. However, in
      situations where the activity volume exceeds the size of one's DLT control
      object, the NLT method should be considered.

PMID- 8550641
TI  - EBRA: a method to measure migration of acetabular components.
AB  - In orthopedics there is a demand for determining migration of hip sockets by
      evaluation of standard radiographs. In this case problems are caused mainly by
      changing pelvis positions on the X-ray table at successive exposures. A method
      (EBRA) is described that evaluates standard AP radiographs without requiring
      additional means at exposure (e.g. ball markers). Simulating the spatial
      situation it computes parameters of longitudinal and transverse migration of
      prosthetic cup and femoral head. A comparability algorithm using a grid of
      transverse and longitudinal tangents of the pelvis contour divides serial
      radiographs into sets of comparable ones. Comparability of serial radiographs
      takes place if the distances of corresponding grid lines do not transcend a given
      limit L. Migration is measured only between comparable radiographs. Different
      studies are described concerning the interdependence of pelvis rotations and
      changes of the grid lines, the degree of pelvis rotations appearing in practice,
      the choice of the limit L, the properties of the comparability algorithm and the
      accuracy of EBRA. The 95% confidence limits for EBRA results are 1.0 mm for
      longitudinal and 0.8 mm for transverse migration.

PMID- 8550642
TI  - Flow visualization with air and smoke in a bypass graft model under steady flow
      conditions.
AB  - A new technique for visualizing the steady flow of a new type of test fluid is
      presented that produces quality photographic results at Reynolds numbers
      typically found in arterial bypass grafts. Room air functions as the test fluid
      and smoke from burning incense sticks provides the tracer particles. As an
      example of this new technique, photographic results are presented for a Reynolds
      number flow of 205 through a Plexiglas model of an end-to-side distal anastomosis
      with a 45 degrees junction angle. The advantages of this technique are that it is
      simple, convenient, and applicable to a wide variety of flow conditions found in
      the human cardiovascular system.

PMID- 8550643
TI  - A comparison of intersegmental joint dynamics to isokinetic dynamometer
      measurements.
AB  - This study quantified the errors associated with measurements obtained using an
      isokinetic dynamometer for knee evaluation at 60 degrees and 180 degrees s-1.
      Five normal subjects were tested. A triaxial electrogoniometer was used to
      measure the kinematics. A custom-designed load cell was used to measure the three
      orthogonal components of the reaction force applied by the isokinetic dynamometer
      to the leg. The inverse dynamics problem was solved to obtain the intersegmental
      dynamics at the knee joint. These data were compared to those obtained from the
      isokinetic dynamometer. The results indicate that the knee motion recorded by the
      isokinetic dynamometer was in error by 7-9 degrees during flexion and 10-13
      degrees during extension. The isokinetic dynamometer recorded knee flexions which
      were less than actual during the flexion portion of the exercise and greater than
      actual during extension. The duration of constant velocity was limited based on
      the speed selected. The knee moment was in error by 5 Nm during flexion and 25-29
      Nm during extension. The use of a gravity correction factor reduced the knee
      moment error during extension, but increased it during flexion.

PMID- 8550644
TI  - ISB recommendations for standardization in the reporting of kinematic data.

PMID- 8550645
TI  - One-stage anterior cervical decompression and posterior stabilization. A study of
      one hundred patients with a minimum of two years of follow-up.
AB  - One hundred patients were managed with one-stage anterior decompression and
      posterior stabilization of the cervical spine. The underlying indication for the
      operation was cervical trauma in thirty-one patients; a neoplasm with a
      pathological fracture or an incomplete neurological deficit in fifty-five; and a
      miscellaneous condition, such as infection, rheumatoid arthritis, or cervical
      spondylotic myelopathy, in fourteen. The duration of follow-up ranged from twenty
      four to 108 months (mean, thirty-two months) for the living patients. Sixteen
      patients had the procedure after the failure of an operation that had been
      performed elsewhere. The development of more biomechanically rigid cervical
      instrumentation did not obviate the need for a combined anterior and posterior
      approach. Twenty-six patients (26 per cent) had supplemental cervical
      instrumentation as part of the circumferential arthrodesis: seventeen had
      insertion of an anterior cervical plate and nine had insertion of a posterior
      facet plate. There were no iatrogenic neurological deficits. Of the seventy-five
      patients who had had a neurological deficit preoperatively, fifty-one improved
      one grade and six improved two grades according to the system of Frankel et al.
      Of the thirty-five patients who had not been able to walk preoperatively, twenty
      one regained enough motor strength to walk postoperatively. Because the anterior
      and posterior procedures were performed during one session of general anesthesia,
      the prevalence of perioperative complications related to the airway was lower
      than that previously reported in the literature. No patient had an obstruction of
      the airway.

PMID- 8550646
TI  - Use of supplemental steroids in patients having orthopaedic operations.
AB  - It is commonly thought that patients receiving exogenous glucocorticoids have
      suppression of the hypothalamic-pituitary-adrenal axis and need high supplemental
      doses of exogenous glucocorticoids (so-called stress steroids) to meet the
      demands of operative stress. Several reports have suggested that clinically
      important suppression of the hypothalamic-pituitary-adrenal axis is extremely
      uncommon and that the levels of glucocorticoids required for stress are much
      lower than previously believed. A prospective study of twenty-eight patients who
      had thirty-five major orthopaedic operations was conducted. No patient received
      stress steroids; they were given only the baseline immunosuppressive doses of
      glucocorticoids (mean dose, ten milligrams of prednisone). Clinical information
      (based on regular physical examinations for signs and symptoms of hypotension,
      myalgia, arthralgia, ileus, and fever) and laboratory data (serum sodium levels,
      eosinophil count, and twenty-four-hour urinary free-cortisol levels, determined
      at perioperative and non-stress postoperative time-periods) were obtained to
      document any evidence of adrenocortical insufficiency. There was no such evidence
      in any of the patients, who were monitored during their entire hospitalization.
      The levels of twenty-four-hour urinary free cortisol showed that all patients had
      endogenous adrenocortical function and, when this information was considered
      together with the clinical outcome, it was concluded that this level of function
      was sufficient to meet the demands of operative stress. Adrenocortical
      insufficiency in patients who have orthopaedic operations without receiving
      supplemental stress steroids appears to be much less common than previously
      thought. While biochemical testing of the function of the hypothalamic-pituitary
      adrenal axis may sometimes reveal evidence of adrenal insufficiency, these tests
      do not predict the clinical outcome and may be too sensitive to guide decisions
      regarding treatment. Supplemental exogenous stress glucocorticoids may not be
      needed to meet the demands of operative stress in these patients.

PMID- 8550647
TI  - The role of intraoperative frozen sections in revision total joint arthroplasty.
AB  - We performed a retrospective analysis of thirty-three consecutive total hip and
      knee (twenty-three hip and ten knee) revision arthroplasties during which
      intraoperative frozen sections were analyzed. Data for the study were collected
      by means of a review of the charts, radiographic analysis, and evaluation of both
      frozen and permanent histological sections. The frozen sections, of
      periprosthetic tissue at the bone-cement interface or the pseudocapsule, were
      considered positive for active infection if there were more than five
      polymorphonuclear leukocytes per high-power field in at least five distinct
      microscopic fields. All patients were available for follow-up, at an average of
      thirty-six months (range, seventeen to seventy-nine months) after the initial
      revision operation. The frozen sections from ten patients were positive for
      infection, and those from twenty-three patients were negative. Comparison of the
      results of the analyses of the frozen sections (both positive and negative) with
      those of the analyses of the permanent histological sections of similar tissue
      showed a correlation of 100 per cent (sensitivity, 1.00; specificity, 1.00; and
      accuracy, 1.00). Nine patients had positive intraoperative cultures, and all of
      them had positive frozen sections (sensitivity, 1.00). Of the twenty-four
      patients who had negative intraoperative cultures, twenty-three had negative
      frozen sections (specificity, 0.96). Of the nine patients who had positive
      intraoperative cultures, only two were found to have infection on intraoperative
      gram-staining. The surgeon's operative assessment regarding the presence of
      infection, compared with the final pathological diagnosis, demonstrated a
      sensitivity of 0.70, a specificity of 0.87, and an accuracy of 0.82. All ten
      patients who had positive frozen sections were managed with excision
      arthroplasty; six of them subsequently had reimplantation, and the excision was
      the definitive procedure in the remaining four. One patient who had had a delayed
      reimplantation had a secondary skin slough and eventually was managed with an
      arthrodesis of the knee. In the group that had negative frozen sections, eighteen
      patients had a primary exchange revision arthroplasty and five had a delayed
      reimplantation. At the time of follow-up, one patient who had had a delayed
      reimplantation had radiographic loosening of the femoral component and was
      asymptomatic. One patient who had had a primary exchange arthroplasty was managed
      with a second revision because of aseptic loosening. There was no clinical
      recurrence of infection in any patient. The data indicate that analysis of frozen
      sections of periprosthetic tissue is a reliable predictor of the presence of
      active infection during revision joint arthroplasty. We recommend its use to
      differentiate aseptic from septic loosening.

PMID- 8550648
TI  - Epidural administration of methylprednisolone and morphine for pain after a
      spinal operation. A randomized, prospective, comparative study.
AB  - The results of postoperative epidural administration of saline solution (a
      placebo), morphine, methylprednisolone, and a combination of morphine and
      methylprednisolone for the reduction of pain after an operation for spinal
      stenosis or a herniated intervertebral disc were compared in a prospective,
      randomized blinded study. Epidural administration of morphine and
      methylprednisolone--either alone or in combination--significantly reduced the
      need for analgesia after an operation for spinal stenosis (p < 0.05) but not
      after an operation for a herniated intervertebral disc. Morphine and
      methylprednisolone did not have an addictive effect on the reduction of pain.
      Itching was significantly more common in the patients who had received morphine
      than in those who had received the placebo (p = 0.04). Although urinary retention
      was more frequent after the use of morphine than after the use of the placebo,
      the difference was not significant with the size of the sample that was analyzed
      (p = 0.25).

PMID- 8550649
TI  - The use of running shoes to reduce plantar pressures in patients who have
      diabetes.
AB  - We compared the plantar pressures generated by walking in leather-soled Oxford
      style shoes and by walking in inexpensive running shoes with those generated by
      walking in thin socks on a hard surface for thirty-nine individuals (thirteen who
      had diabetes and neuropathy, and thirteen who had diabetes without neuropathy,
      and thirteen who had neither diabetes nor neuropathy [controls]). Except for two
      anatomical regions, the plantar pressure associated with the Oxford-style shoes
      were not different from those associated with walking without shoes. In
      comparison, the inexpensive running shoes relieved plantar pressure in the
      forefoot and heel by a mean (and standard deviation) of 31 +/- 9.1 per cent, with
      the most relief occurring in the feet that had the highest pressures when they
      were unshod. There were significant reductions in pressure in all regions of the
      foot except for the midfoot (p < 0.01), and there were no significant differences
      between the groups. Individuals who have insensate feet should be discouraged
      from wearing leather-soled Oxford-style shoes because of the risk of ulceration
      due to elevated plantar pressures. Inexpensive running shoes should be viewed as
      the very minimally acceptable choice for footwear for these individuals if the
      feet are free of deformity.

PMID- 8550650
TI  - Early failure of acetabular components inserted without cement after previous
      pelvic irradiation.
AB  - The effect of previous irradiation of the pelvis on the survival of acetabular
      components inserted without cement in primary total hip arthroplasty was
      examined. We searched a database of 1319 patients who had been managed with a
      primary total hip arthroplasty with insertion of a hemispherical porous-coated
      acetabular component without cement. This revealed twelve hips in eleven patients
      who had been managed with previous irradiation of the pelvis. Three patients had
      died after less than one year of follow-up, leaving eight patients with nine
      acetabular components available for study at an average of thirty-seven months
      (range, seventeen to seventy-eight months) after the operation. The type of
      radiation as well as the fractionation, dose, and portals were reviewed to
      determine the exposure of the periacetabular region to radiation. Failure of the
      component was assessed radiographically and clinically. At the time of follow-up,
      three of the nine acetabular components had migrated, as seen on radiographs, and
      had been associated with progressive radiolucency without clinical symptoms.
      Thus, four of the nine acetabular components failed, at an average of twenty-five
      months (range, sixteen to thirty-eight months). The other five components had not
      failed clinically and were stable radiographically at an average of thirty-six
      months (range, seventeen to sixty-three months). The insertion of acetabular
      components without cement in a previously irradiated pelvis has a high rate of
      failure. However, a superior method of acetabular reconstruction in this
      difficult situation has yet to emerge.

PMID- 8550651
TI  - Failure of intraoperatively customized non-porous femoral components inserted
      without cement in total hip arthroplasty.
AB  - Seventy-four primary total hip arthroplasties were performed in sixty-eight
      patients between August 1990 and September 1991. Clinical assessments were made
      with use of the Harris hip score and, specifically, the pain component of that
      score. The preoperative radiographs were digitally quantified for calculation of
      the so-called canal-to-calcar ratio and the so-called cortical index. The
      postoperative radiographs were evaluated for the percentage of the cross
      sectional area of the femoral canal that was occupied by the prosthesis;
      subsidence of the prosthesis; and adaptive osseous changes, including
      hypertrophic cortical remodeling, osteolysis, formation of sclerotic radiolucent
      lines around the prosthesis, and formation of a pedestal at the tip of the
      prosthesis. The indication for the arthroplasty was osteoarthrosis in fifty hips
      (68 per cent), avascular necrosis in fourteen (19 per cent), congenital dysplasia
      in six (8 per cent), and another diagnosis in four (5 per cent). The average
      duration of follow-up was thirty-one months (range, eleven to forty-six months).
      The average Harris hip score (and standard deviation) was 75 +/- 16.8 points
      (range, 29 to 100 points), and the average score for the pain component was 37 +/
      7.5 points (range, 0 to 44 points). The average canal-to-calcar ratio of the
      hips was 0.44 (range, 0.32 to 0.74), and the average cortical index was 0.54
      (range, 0.33 to 0.66). The average subsidence of the component was 0.6 centimeter
      (range, 0.0 to 2.3 centimeters). The average fill of the canal was 100 per cent
      proximally, 97 per cent at the middle of the stem, and 92 per cent distally as
      measured on the anteroposterior radiographs made immediately postoperatively and
      100, 95, and 90 per cent, respectively, as measured on the lateral radiographs. A
      failure occurred in twenty-one hips (28 per cent) in twenty-one patients, with an
      average time to failure of 21 +/- 13 months (range, one to forty-four months).
      The Kaplan-Meier survival estimate (and standard error) for this population was
      0.45 +/- 0.11 (confidence interval, 0.67 to 0.23) at forty-four months. The
      average subsidence of the components that failed was 0.7 centimeter (range, 0.1
      to 2.3 centimeters). There was no significant relationship between failure of the
      component and the age or sex of the patient, the diagnosis, or the side of the
      operation. Postoperative severity of pain (p = 0.09) or subsidence (p = 0.08)
      alone did not reach significance for predicting outcome. The Harris hip score
      alone (p = 0.05), the Harris hip score in combination with subsidence of the
      femoral component (p = 0.01), and the pain component of the Harris hip score in
      combination with subsidence of the femoral component (p = 0.01) were all
      significant for predicting outcome. No other measured radiographic variable was
      predictive of failure. Despite optimization of the fit of the component within
      the femoral canal and the percentage of the cross-sectional area of the femoral
      canal occupied by the component, the clinical results indicated a high rate of
      failure. Thus, these criteria are not the only requisites for stabilization of
      these femoral components without cement. On the basis of these data, we have
      discontinued the use of these intraoperatively customized, non-porous, smooth
      femoral prosthesis.

PMID- 8550652
TI  - Total hip arthroplasty with use of so-called second-generation cementing
      techniques. A fifteen-year-average follow-up study.
AB  - One hundred and forty-nine patients (162 hips) had a standard primary total hip
      arthroplasty with a grit-blasted femoral component and use of so-called second
      generation cementing techniques. No patient was lost to follow up. Fifty-one
      patients (sixty hips) died within fourteen years after the index operation. The
      remaining ninety patients (102 hips) were followed for a minimum of fourteen
      years. Of the fifty-one patients (sixty hips) who died within fourteen years,
      three patients (three hips; 5 per cent) had had a revision: one, because of
      aseptic loosening of the acetabular component; one, because of aseptic loosening
      of the femoral component; and one because of aseptic loosening of both
      components. Of the ninety patients (102 hips) who were alive fourteen years or
      more (average duration of follow-up, fifteen years) after the arthroplasty, one
      patient (two hips; 2 per cent) had a revision because of bilateral aseptic
      loosening of the femoral component. In seven patients (seven hips; 7 per cent),
      the femoral component loose according to radiographic criteria but was not
      revised. For the entire group of 162 hips, four femoral components (2 per cent)
      were revised because of aseptic loosening. In contrast, the rate of aseptic
      loosening of the acetabular component was higher and continued to increase. Of
      the eighty-one hips with an all-polyethylene acetabular component in the patients
      who were alive at fourteen years or more, eight (10 per cent) had a revision
      because of aseptic loosening. In addition, twenty-eight (42 per cent) of the
      sixty-seven all-polyethylene acetabular components that were in place after
      fourteen years or more, and for which there were current radiographs, were loose.
      Femoral components implanted with the use of second-generation cementing
      techniques appear to have fared much better than acetabular components that were
      inserted with similar techniques in this series of patients. A thin (less than
      one-millimeter) mantle of cement around the femoral component and defects in the
      mantle of cement were associated with increased loosening of the femoral
      component.

PMID- 8550653
TI  - Median-nerve neuropathy associated with chronic anterior dislocation of the
      lunate.
AB  - Ten patients who had median-nerve neuropathy in association with chronic anterior
      dislocation of the lunate were managed operatively and were followed for an
      average of five years (range, three to eight years). The average time from the
      injury to the initial evaluation was twenty-one months (range, six to sixty-five
      months). All ten patients had pain as well as sensory and motor dysfunction in
      the distribution on the median nerve. Nerve-conduction-velocity studies revealed
      a delay in distal motor and sensory latencies in all patients; the distal motor
      latency averaged 12.5 milliseconds (range 5.6 to 18.6 milliseconds), and the
      distal sensory latency averaged 12.4 milliseconds (range, 4.8 to 16.8
      milliseconds). Three patients had had a failed carpal tunnel release and needed
      excision of the lunate for decompression of the median nerve. In the other seven
      patients, three distinctive sites of nerve compression were identified: the volar
      and dorsal edges of the lunate and the proximal edge of the transverse carpal
      ligament. Excision of the osseous protuberance (excision of the lunate in three
      patients and a proximal-row carpectomy in four), combined with a release of the
      transverse carpal ligament, resulted in relief of the symptoms, functional
      improvement, and sensory and motor recovery in the distribution of the median
      nerve.

PMID- 8550654
TI  - Tendon-healing to cortical bone compared with healing to a cancellous trough. A
      biomechanical and histological evaluation in goats.
AB  - This study was performed to test the hypothesis that attaching a tendon to a
      trough in cancellous bone results in tendon-healing that is biomechanically
      superior to that after direct fixation of a tendon to cortical bone. Twenty adult
      female goats were treated with a bilateral tenotomy of the infraspinatus tendon
      with subsequent reattachment of the tendon. In shoulders randomized to the
      cancellous-fixation group, a cancellous bed was prepared with a motorized burr
      and a template measuring twenty by five by five millimeters. The repair in the
      shoulders randomized to the cortical-fixation group was performed in the same
      manner, except that the tendon was attached to cortical bone. Three outcome
      measures were assessed, six and twelve weeks after the repair, with the Student
      paired t test and analysis of variance: load to failure, energy to failure, and
      stiffness. The types of repair were not significantly different with regard to
      any of the three outcomes. When the six and twelve-week data were combined, an
      average difference in load to failure of 3.9 per cent in favor of cancellous
      repair was observed but it was not significant (p = 0.78). The associated 95 per
      cent confidence interval for the difference ranged from 10.5 per cent in favor of
      cortical repair to 18.3 per cent in favor of cancellous repair. Histological
      analysis at six and twelve weeks revealed progressive maturation and
      reorganization of the bone-tendon interface with re-establishment of collagen
      fiber continuity between the tendon and bone. This process was indistinguishable
      between the cortical and cancellous specimens. This study demonstrated no
      significant benefit from the creation of a trough to expose the tendon to
      cancellous bone. In this model, at both six and twelve weeks, the tendon-to-bone
      healing process of the two groups appeared similar and the biomechanical
      properties were approximately equal.

PMID- 8550655
TI  - Arthrodesis of the ankle with a free vascularized autogenous bone graft.
      Reconstruction of segmental loss of bone secondary to osteomyelitis, tumor, or
      trauma.
AB  - Reconstruction after massive loss of bone about the ankle is difficult because of
      the limited amount of surrounding soft tissue and because of technical factors
      pertaining to adequate internal or external fixation. Conventional techniques are
      often unsuccessful because of the frequency of associated deep infection and of
      previous operative procedures. In this report, we describe eleven patients with a
      large defect of the distal aspect of the tibia who were managed at our
      institution with arthrodesis of the ankle with free vascularized bone graft. The
      defect was related to a tumor resection; an acute open fracture with bone and
      soft-tissue loss caused by a shotgun injury; or osteomyelitis, either alone or in
      combination with septic arthritis, with chronic non-union following a fracture of
      the ankle. A free fibular graft was used in osseous defects that were larger than
      four centimeters, and a free iliac-crest graft was used in smaller defects.
      Osteocutaneous or osteomuscular flaps were constructed to cover accompanying soft
      tissue defects when necessary. A successful fusion was obtained in nine of the
      eleven patients. The results in the remaining two were regarded as clinical
      failures, and a below-the-knee amputation was performed. One amputation was done
      because of recurrent infection and the other, because of failure of the fracture
      to unite after four years.

PMID- 8550656
TI  - Proximal femoral focal deficiency: results of rotationplasty and Syme amputation.
AB  - We reviewed the results of treatment of sixteen patients who had had an isolated
      unilateral proximal femoral focal deficiency; nine were managed with a
      rotationplasty and seven, with a Syme amputation combined with an arthrodesis of
      the knee. We evaluated the perceived physical appearance, gross motor function,
      and metabolic energy expended in walking. The mean duration of follow-up was 9.9
      years (range, four to fourteen years). The mean age of the patients at the time
      of the study was 13.9 years (range, eight to 18.4 years) in the rotationplasty
      group and 14.8 years (range, 9.5 to 19.9 years) in the Syme-amputation group.
      There were three female patients in each group. Roentgenograms showed that the
      femoral head was in the acetabulum (Aitken class A or B) in four of the seven
      patients in the Syme-amputation group and in five of the nine patients in the
      rotationplasty group; the remaining patients did not have this finding (Aitken
      class C or D). There was no difference in gross motor function or perceived
      physical appearance between the groups. Rotationplasty was associated with a more
      energy-efficient gait (mean, 0.153 milliliter of oxygen per kilogram-meter
      [range, 0.128 to 0.173 milliliter of oxygen per kilogram-meter] than was Syme
      amputation (mean, 0.169 milliliter of oxygen per kilogram-meter [range, 0.151 to
      0.182 milliliter of oxygen per kilogram-meter]). Both types of treatment resulted
      in a net oxygen utilization per distance (efficiency) that was less than the
      values reported after amputations performed for non-congenital disorders.

PMID- 8550657
TI  - Erroneous interpretation of magnetic resonance images of a fracture of the first
      rib with non-union. Two case reports.

PMID- 8550658
TI  - Transient phalangeal osteolysis (microgeodic disease). Report of a case involving
      the foot.

PMID- 8550659
TI  - Snapping brachialis tendon associated with median neuropathy. A case report.

PMID- 8550660
TI  - Anomalous insertion of the medial meniscus of the knee. A case report.

PMID- 8550661
TI  - An excavation of the distal femoral metaphysis: a magnetic resonance imaging
      study. A case report.

PMID- 8550662
TI  - Pharmacological treatment of soft-tissue injuries.

PMID- 8550663
TI  - Range-of-motion measurements.

PMID- 8550664
TI  - Range-of-motion measurements.

PMID- 8550665
TI  - Restoration of the osteoarthrotic joint.

PMID- 8550666
TI  - Septic arthritis associated with brachial plexus neuropathy. A case report.

PMID- 8550667
TI  - Benign giant-cell tumor of bone with metastasis to mediastinal lymph nodes. A
      case report of resection facilitated with use of steroids.

PMID- 8550668
TI  - Fatal pulmonary embolism during manipulation after total knee arthroplasty. A
      case report.

PMID- 8550669
TI  - The use of radiographic imaging studies in the evaluation of patients who have
      degenerative disorders of the lumbar spine.

PMID- 8550670
TI  - The natural history of osteonecrosis of the femoral head in children and
      adolescents who have Gaucher disease.
AB  - We reviewed the cases of eight patients (thirteen hips) with Gaucher disease who
      had had osteonecrosis of the femoral head and had been managed with bed rest and
      non-weight-bearing with crutches only in the symptomatic stage of the bone
      crisis. The mean age of the patients at the onset of the first crisis in each hip
      was ten years (range, six to fourteen years). The mean age at the most recent
      follow-up examination for the six living patients (ten hips) was twenty-three
      years (range, nineteen to thirty-three years). The Mose rating was good for one
      hip, fair for two, and poor for seven. Despite the over-all unfavorable
      radiographic ratings, the six patients were asymptomatic and did not need
      assistance with daily activities. There is no known treatment that effectively
      prevents the development of deformities of the femoral head. Thus, we recommend
      symptomatic management for osteonecrosis of the femoral head in Gaucher disease
      with bed rest and analgesics followed by non-weight-bearing on the involved limb,
      if it makes the patient more comfortable, during the symptomatic stage of bone
      crisis.

PMID- 8550671
TI  - Clinical results after tarsal tunnel decompression.

PMID- 8550672
TI  - Persistent leakage of cerebrospinal fluid after intrathecal administration of
      morphine in an operation on the lumbar spine. A report of two cases.

PMID- 8550673
TI  - Effectiveness of treatment with a brace in girl who have adolescent idiopathic
      scoliosis. A prospective, controlled study based on data from the brace study of
      the scoliosis research society.

PMID- 8550674
TI  - Oblique osteotomy for the correction of tibial malunion.

PMID- 8550675
TI  - Results of the Wagner and Ilizarov methods of limb-lengthening.
AB  - We compared the results of the Wagner method of limb-lengthening in twenty
      extremities (nineteen patients) with those of the Ilizarov method in twenty-one
      extremities (eighteen patients). The Wagner external fixator was used in all
      twenty procedures in which the Wagner lengthening method was performed and in
      fourteen procedures in which the Ilizarov lengthening method was performed. The
      Ilizarov external fixator was used in the remaining seven procedures in which the
      Ilizarov method was performed. The average increase in length was 5.4 centimeters
      (range, 2.8 to 8.0 centimeters) with the Wagner technique and 5.9 centimeters
      (range, 1.0 to 16.8 centimeters) with the Ilizarov technique. The rate for the
      lengthening phase was nine days for one centimeter of length with the Wagner
      technique and twelve days for one centimeter with the Ilizarov technique. The
      rate for the consolidation phase was forty-four days for one centimeter with the
      Wagner technique and twenty-six days for one centimeter with the Ilizarov
      technique. The group of patients who were managed with the Wagner technique had
      thirty major complications, and the group of patients who were managed with the
      Ilizarov technique had only thirteen major complications. Forth complications
      were associated with the use of the uniaxial Wagner external apparatus and
      sixteen, with the use of the multiaxial Ilizarov external fixator.

PMID- 8550676
TI  - Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg
      Perthes disease.
AB  - Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes
      disease were found to have coagulation abnormalities. Twenty-three children had
      thrombophilia (a deficiency in antithrombotic factor C or S, with an increased
      tendency toward thrombosis); nineteen of the twenty-three children had protein-C
      deficiency and four had protein-S deficiency. Seven children had a high level
      (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic
      lipoprotein associated with osteonecrosis in adults. Three children had
      hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children
      when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the
      mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of
      the first-degree relatives of eleven of the nineteen probands who had a low
      protein-C level had a low protein-C level as well; all of these low levels
      represented previously undiagnosed familial protein-C deficiency. The eleven
      probands who had familial protein-C deficiency were more likely to have early
      onset of Legg-Perthes disease (at or before the age of five years) than the
      eleven children who had normal levels of protein C, protein S, and lipoprotein(a)
      as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least
      one first-degree relative of one of the four probands who had a low protein-S
      level had a low protein-S level and previously undiagnosed familial protein-S
      deficiency. At least one first-degree relative of six of the seven probands who
      had a high level of lipoprotein(a) had a familial high level of lipoprotein(a).
      Six of the seven children who had a high level of lipoprotein(a) also had a low
      level of stimulated tissue-plasminogen activator activity, the major initiator of
      fibrinolysis. At least one first-degree relative of one of the three probands who
      had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated
      tissue-plasminogen activator activity also had low stimulated tissue-plasminogen
      activator activity (familial hypofibrinolysis). Legg-Perthes disease,
      thrombophlebitis, premature myocardial infarction, and stroke, which are
      ramifications of the familial thrombophilic-hypofibrinolytic disorders, were
      common in the first and second-degree relatives of the thirty-three children with
      Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.

PMID- 8550677
TI  - Congenital dislocation of the hip in the older child. The effectiveness of
      overhead traction.
AB  - We studied the use of overhead traction in the treatment of congenital
      dislocation of the hip in thirty-five children (fifty hips) whose mean age at the
      time of the diagnosis was thirty-three months (range, eighteen to seventy-two
      months). None of the children had had any previous treatment. The mean time in
      traction was twenty-three days (range, eight to thirty-six days). Closed
      reduction was successful for relocation of the femoral head in thirty-eight of
      the fifty hips; twenty of these hips needed no additional treatment, sixteen were
      treated with an innominate osteotomy because of severe acetabular dysplasia, and
      two needed femoral derotation and an innominate osteotomy to correct persistent
      subluxation. In the remaining twelve hips, closed reduction failed at the outset
      and an open reduction was necessary. Femoral shortening also was performed in
      seven of the twelve hips to maintain concentric reduction. After a mean duration
      of follow-up of forty-eight months (range, thirty-two to sixty-five months),
      thirty-three hips were rated as class 1; seven, as class 2; four, as class 3; and
      five, as class 4, according to the criteria of Severin. The remaining hip could
      not be so classified. Avascular necrosis developed in two hips that had been
      treated with closed reduction followed by Salter osteotomy and in three hips that
      had been treated with primary open reduction. We found that preliminary overhead
      traction facilitated closed reduction of untreated congenitally dislocated hips
      in children who were eighteen to seventy-two months old.

PMID- 8550678
TI  - Healing of a segmental defect in the rat femur with use of an extract from a
      cultured human osteosarcoma cell-line (Saos-2). A preliminary report.
AB  - Devitalized extracts from cultured human osteosarcoma cells (Saos-2) can induce
      ectopic bone formation. The ability of an extract from Saos-2 cells to stimulate
      healing of an operatively created four-millimeter defect in the femoral diaphyses
      of rats was compared with that of collagen and that of autogenous bone graft.
      Forty adult rats were randomized into four groups of ten each. In Group 1
      (controls), no material was placed in the defect; in Group 2, the defect was
      filled with pure bovine collagen; in Group 3, it was filled with autogenous graft
      obtained by morseling of the resected segment of the femur; and in Group 4, it
      was filled with ten milligrams of extract from Saos-2 cells that was mixed with
      an equal amount of bovine collagen. Five rats from each group were killed at four
      weeks and the remaining five, at eight weeks. Each femoral defect was analyzed
      radiographically and histologically for osseous healing. There was no evidence of
      healing at either four or eight weeks in Groups 1 and 2. Although there was some
      new-bone formation in Group 3, none of the defects had united at eight weeks.
      There was early, almost complete union in all five four-week specimens in Group 4
      and complete healing of the defect in four of the five rats assessed at eight
      weeks. The Saos-2 cell extract was found to be the most effective agent,
      promoting union by mature lamellar bone within eight weeks.

PMID- 8550679
TI  - Coronal shear fractures of the distal end of the humerus.
AB  - We identified a shear fracture of the distal articular surface of the humerus,
      with anterior and proximal displacement of the capitellum and a portion of the
      trochlea, in six patients (five female and one male). The average age of the
      patients was thirty-eight years (range, ten to sixty-three years). Each fracture
      was the result of a fall from a standing height. A characteristic radiographic
      abnormality, which we have termed the double-arc sign, was seen on the lateral
      radiograph of each patient and represented the subchondral bone of the displaced
      capitellum and the lateral trochlear ridge. All patients were managed with open
      reduction, internal fixation, and early motion of the elbow. The average duration
      of follow-up was twenty-two months (range, eighteen to twenty-six months). The
      fracture united in all patients at an average of six weeks (range, four to nine
      weeks), without radiographic evidence of osteonecrosis of the fracture fragment.
      Flexion of the elbow averaged 141 degrees (range, 130 to 150 degrees), with an
      average flexion contracture of 15 degrees (range, 0 to 40 degrees). Pronation of
      the forearm averaged 83 degrees, and supination averaged 84 degrees. All patients
      had a good or excellent functional result, according to the elbow-rating scale of
      Broberg and Morrey.

PMID- 8550680
TI  - Total hip replacement for coxarthrosis secondary to congenital dysplasia and
      dislocation of the hip. Long-term results.
AB  - Between 1970 and 1982, sixty-six total hip replacements were performed with
      cement, without bone-grafting, in fifty-three patients who had congenital
      dysplasia and dislocation of the hip. Preoperatively, the patients had had Crowe
      type-II, III, or IV subluxation. Current information was available for fifty-nine
      hips in forty-six patients after an average duration of follow-up of sixteen
      years (range, ten to twenty-one years). The average age of the patients at the
      time of the operation was fifty-three years (range, twenty-three to seventy-three
      years). The average Harris hip score at the most recent examination was 92 points
      (range, 61 to 100 points). Eight hips were revised. The reason for the revision
      was infection in two hips, fracture of the femoral stem in two, and loosening of
      the acetabular component in four. The rate of revision for aseptic loosening,
      therefore, was 10 per cent (six hips). In the unrevised hips for which
      radiographs were available, the rate of radiographic loosening of the femoral
      component was 5 per cent (two hips) and that of the acetabular component was 32
      per cent (twelve hips). We did not find a relationship between the amount of
      horizontal or vertical displacement of the center of the femoral head and the
      rate of loosening. Kaplan-Meier survivorship analysis with revision as the end
      point predicted a rate of survival of 85 per cent (95 per cent confidence
      interval, 75 to 95 per cent) at fifteen years. With radiographic loosening as the
      end point, the predicted rate of survival was 68 per cent (95 per cent confidence
      interval, 54 to 81 per cent) at fifteen years. We concluded that, for patients
      who have Crowe type-II, III, or IV congenital dysplasia of the hip, good long
      term results can be obtained with insertion of a femoral stem with cement. The
      high rate of loosening of cemented acetabular components is a concern.

PMID- 8550681
TI  - The effects of recombinant human erythropoietin on perioperative transfusion
      requirements in patients having a major orthopaedic operation. The American
      Erythropoietin Study Group.
AB  - Two hundred patients who were scheduled for a major elective orthopaedic
      operation were enrolled in a prospective study and were randomly assigned to one
      of three treatment groups. Group 1 consisted of sixty patients who received
      recombinant human erythropoietin, 300 international units per kilogram of body
      weight per day; Group 2, seventy-one patients who received recombinant human
      erythropoietin, 100 international units per kilogram of body weight per day; and
      Group 3, sixty-nine patients who received a placebo. A total of fifteen doses was
      given subcutaneously, beginning ten days before the operation and extending
      through the fourth postoperative day. Patients who declined or were unable to
      donate autologous blood preoperatively were included in the study and were
      maintained on iron supplementation orally. The decision to transfuse red blood
      cells depended on the physician, however, physicians were encouraged not to do so
      if the hematocrit was more than 0.27 (27 per cent), unless the clinical symptoms
      warranted it. Of the 185 patients who were evaluable with regard to efficacy,
      significantly fewer patients received homologous red-blood-cell transfusions in
      Groups 1 and 2 (17 per cent [nine] and 25 per cent [sixteen], respectively) than
      in Group 3 (54 per cent [thirty-six]) (p < 0.001). When the patients were
      stratified into two groups on the basis of the pre-treatment hemoglobin level
      (more than 100 to 130 grams per liter or more than 130 grams per liter), we found
      that patients who had received a placebo and had a baseline hemoglobin level of
      more than 100 to 130 grams per liter were at significantly higher risk for
      transfusion (78 per cent [twenty-one]) than those who had received a placebo and
      had a baseline level of more than 130 grams per liter (36 per cent [fourteen]).
      For patients who had a baseline hemoglobin level of more than 100 to 130 grams
      per liter, the higher dose of recombinant human erythropoietin appeared somewhat
      more effective than the lower dose, with 14 per cent (three) of the patients in
      Group 1 and 39 per cent (nine) in Group 2 needing a transfusion; however, the
      difference was not significant (p = 0.09). For patients who had a baseline
      hemoglobin level of more than 130 grams per liter, the two doses of recombinant
      human erythropoietin produced similar results, with 14 per cent (four) of the
      patients in Group 1 and 11 per cent (four) in Group 2 needing a transfusion; this
      was in contrast to a rate of transfusion of 36 per cent (fourteen) in Group 3
      (the patients who received the placebo) (p = 0.03). The recombinant human
      erythropoietin was generally well tolerated, although one patient, who did not
      have a history of hypertension, had an increase in blood pressure, from a
      baseline level of 142/78 millimeters of mercury (18.93/10.40 kilopascals) to a
      level of 220/100 millimeters of mercury (29.33/13.33 kilopascals), after ten days
      of treatment with the higher dose. These data suggest that recombinant human
      erythropoietin, administered before and after major orthopaedic operations, can
      minimize the need for homologous red-blood-cell transfusion.

PMID- 8550682
TI  - Total hip arthroplasty with the Charnley prosthesis in patients fifty-five years
      old and less. Fifteen to twenty-one-year results.
AB  - Data on 240 primary Charnley total hip arthroplasties, performed in 211 patients
      from October 1968 to July 1974, were recorded prospectively. Fifty-two prostheses
      were implanted in forty-six patients who were thirty-four to fifty-five years
      old, and 188 prostheses were implanted in 165 patients who were more than fifty
      five years old. The results for the younger patients were compared with those for
      the older patients. Twenty hips were revised over-all, and all five of the
      infections and four of the five fractures of the femoral stem that occurred in
      this group were in the older patients. However, the rate of aseptic loosening was
      similar for the two age-groups (three of the hips in the younger patients and
      five in the older patients). The probability of revision after twenty years for
      the two groups, as determined with Kaplan-Meier analysis, was 11.7 per cent for
      the younger patients and 10.7 per cent for the older patients. There was no
      significant difference between the two groups with regard to either the number of
      revisions or the percentage of patients who had radiographic signs of loosening.
      The median Charnley hip scores during the course of the study were also similar
      for the two groups. We recommend that Charnley low-friction arthroplasty be used
      even in younger patients, as the long-term results were excellent and were
      comparable with those in the elderly age-group.

PMID- 8550683
TI  - The elevated-rim acetabular liner in total hip arthroplasty: relationship to
      postoperative dislocation.
AB  - Although an acetabular component with an elevated rim is thought to improve the
      postoperative stability of a total hip prosthesis, the actual clinical value has
      not yet been demonstrated. To address this question, we reviewed the results of
      5167 total hip arthroplasties that had been performed at our institution from
      April 1, 1985, through December 31, 1991. The prostheses included 2469 acetabular
      components with an elevated-rim liner (10 degrees of elevation) and 2698 with a
      standard liner. The cumulative probability of dislocation was estimated as a
      function of time since the operation with use of the Kaplan-Meier survivorship
      method. Forty-eight of the 2469 hips that had the elevated-rim acetabular liner
      dislocated within two years, compared with 101 of the 2698 hips that had the
      standard acetabular liner. The two-year probability of dislocation was 2.19 per
      cent for the hips with the elevated-rim liner and 3.85 per cent for those with
      the standard liner (p = 0.001). A similar trend was seen at five years; however,
      because of a smaller sample the difference was not significant. Increased
      stability at two years was also demonstrated for the hips with the elevated-rim
      liner when the hips were analyzed according to the operative approach, the mode
      of fixation, the sex of the patient, and the type of total hip arthroplasty
      (primary or revision). Although these data demonstrate improved stability after
      total hip arthroplasty when an elevated liner is used, particularly in hips that
      are at greater risk for dislocation of the prosthesis, the long-term effect of
      this elevated liner on wear and loosening remains unknown but is of considerable
      concern. The elevated liner deserves additional study to clarify its effect on
      wear and loosening.

PMID- 8550684
TI  - Revision total hip arthroplasty with cement after cup arthroplasty. Long-term
      follow-up.
AB  - Ninety-six cup arthroplasties (eighty-three patients) were converted to total hip
      arthroplasties with cement between July 1970 and August 1982. Fifty-eight hips
      (fifty patients) were followed for at least ten years, or to failure after a
      shorter interval, and eight other hips (eight patients) had a subsequent
      operation because of a deep infection. Of the fifty-eight hips that were followed
      for at least ten years or to failure, nine (16 per cent) were revised because of
      aseptic loosening of the acetabular component, one (2 per cent) was revised
      because of a traumatic fracture of the femur, and none were revised because of
      loosening of the femoral component. Kaplan-Meier survivorship analysis with
      revision for any reason (including infection) as the end point showed a rate of
      survival of 92 +/- 6 per cent (average and 95 per cent confidence interval) at
      ten years and of 74 +/- 12 per cent at twenty years. When the hips in which an
      infection had occurred were excluded, and with revision because of aseptic
      loosening of the acetabular component as the end point, the rate of survival was
      84 +/- 10 per cent at twenty years; no acetabular component was revised because
      of aseptic loosening in the first ten years. When the hips in which an infection
      had occurred were excluded, and with radiographic evidence of definite or
      probable loosening of the acetabular component, or aseptic loosening of the
      acetabular component necessitating revision, as the end point, the rate of
      survival was 91 +/- 6 per cent at ten years and 53 +/- 22 per cent at twenty
      years. The present study demonstrates the durability of total hip replacement
      with cement after the failure of a cup arthroplasty and further substantiates the
      excellent long-term clinical and radiographic results that can be obtained with
      insertion of a femoral component with cement.

PMID- 8550685
TI  - Effect of a chondral-labral defect on glenoid concavity and glenohumeral
      stability. A cadaveric model.
AB  - One of the primary stabilizing mechanisms of the glenohumeral joint is concavity
      compression, the maintenance of the humeral head in the concave glenoid fossa by
      the compressive force generated by the surrounding muscles. This mechanism is
      active in all glenohumeral positions but it is particularly important in the
      functional mid-range, in which the capsule and ligaments are slack. The
      effectiveness of concavity-compression in the stabilization of a joint can be
      characterized in terms of the ratio between the maximum dislocating force that
      can be stabilized in a given direction and the load compressing the head into the
      glenoid (the stability ratio). Glenoid concavity can be described by the lateral
      humeral displacement during translation across the glenoid. The purpose of the
      present investigation was to characterize the concavity and stability ratios of
      normal cadaveric glenoids, to measure the effect of an anteroinferior chondral
      labral defect on these parameters, and to measure the effectiveness of a
      simulated operative reconstruction on the restoration of glenoid concavity and
      the stability ratio. The chondral-labral defect created in this study reduced the
      height of the glenoid by approximately 80 per cent and the stability ratio by
      approximately 65 per cent for translation in the direction of the defect.
      Reconstruction of the anteroinferior aspect of the glenoid concavity with use of
      an autogenous biceps-tendon graft restored normal values for these variables.

PMID- 8550686
TI  - Stress and self-care revisited: a literature review.
AB  - This review of self-care focuses on key theorists and their models, relevant
      research findings, and interventions that create changes in the cognitive,
      behavioral, and physical well-being of individuals. The article also provides a
      review of the theory underlying self-care and the influence of related
      disciplines on the concept. After a discussion of potential barriers, the
      determinants of these health-promoting behaviors are addressed. The review of
      stress focuses almost exclusively on studies that suggest helpful coping
      mechanisms for nurses in the workplace. Key variables addressed include the
      hardiness dimension and the organizational climate necessary for a supportive
      workplace.

PMID- 8550687
TI  - Awakening the nurse healer within.
AB  - Nurses help individuals, families, groups, and communities promote health, reduce
      health-risking behavior, increase self-care management skills, and facilitate
      personal growth toward wholeness of mind, body, and spirit. To care for others
      and to promote health and well-being, nurses must first understand the role of
      healer and second practice personal care. The article provides a framework for
      both understanding the role of healer and engendering self-care and healing by
      introducing methods to care for ourselves, acknowledging the importance of
      knowledgeable and compassionate caregiving, and creating a vision for the future
      of health care and nursing.

PMID- 8550688
TI  - The Japanese Tea Ceremony and stress management.
AB  - When people attend a Japanese Tea Ceremony, they often remark that it had a
      calming effect on them. The Tea Ceremony can be much more than that, however.
      Serious practitioners of tea develop a mind set and body control that enables
      them to transform tension-producing details of everyday life into moments of
      beauty, meaningfulness and tranquility. This effect comes from ritualizing
      ordinary chores and giving them an esthetic dimension and a noble motivation.
      Such discipline of mind and body also enables tea people to concentrate solely on
      the present moment, thereby shutting out worries about the past and anxieties
      about the future.

PMID- 8550689
TI  - Vitality for caregivers.
AB  - Changes such as increased patient acuity, shorter hospital stays, workplace
      reorganization, revision of the nursing role, and the development of home care
      services all contribute to high stress rates for health care workers. Research
      results on vitality are presented from three nursing professionals with
      backgrounds in education, psychotherapy, holistic nursing, and energy-based
      practice. Six key elements associated with vitality are described. The
      application of these principles by nursing leadership and the use of educational
      principles to create a vehicle for making this information to caregivers are
      described. The outcome, Vitality Training, is an effective approach that
      delineates methods for revitalizing and reawakening the ideals of the nursing
      profession and maintaining personal energy and enthusiasm.

PMID- 8550690
TI  - Humor: an antidote for stress.
AB  - Humor and laughter can be effective self-care tools to cope with stress. An
      ability to find humor gives us a sense of perspective on our problems. Laughter
      provides a physical release for accumulated tension. The article reviews research
      on the effect of humor and laughter on our immune function and resilience to
      stress. Resources for finding humor are included.

PMID- 8550691
TI  - Caring for self: becoming a self-reflective nurse.
AB  - Grounded in teaching experiences with nursing students, Dewey's educational
      philosophy, principles of adult learning, and phenomenologic perspectives, the
      article presents a model of self-reflection discovered in the
      educational/learning process of caring for self. Self-reflection as a process is
      operationalized as a bending back of attention and a focus on self to uncover
      silence and meanings or essences of personal and professional experience.
      Critical outcomes of this process are increased awareness, increased depth and
      breadth of understanding, and expanded consciousness. The thesis that self
      reflection is a critical process in caring for others is presented. The
      background for the work and the nursing course where students develop a clinical
      experience of caring for self are discussed. The article includes graphic
      representations of the reflective process and proposes that, through caring for
      self, transformation in caring experiences is possible.

PMID- 8550692
TI  - Congruency between nurses' values and job requirements: a call for integrity.
AB  - Values are an integral part of human existence; they select the priorities we
      live by and shape our way of being in the world. Living outside our value system
      is exhausting because our inner and outer worlds are not congruent with one
      another. Organizations must provide a variety of work roles reflecting a range of
      value sets to integrate staff at differing stages of value development.
      Individuals must know and honor their own values by living authentic, courageous
      lives through making career choices that are congruent with their values while
      honoring the unique career choices of their colleagues. Values are related to
      skills, and through skill acquisition more complex values are acquired. Through
      the development of interpersonal, imaginal, and systems skills, individuals and
      organizations can expand their capacity for caring and innovation in holistic and
      life-giving ways.

PMID- 8550693
TI  - Creating a work environment that supports self-care.
AB  - The article challenges health care institutions to take corporate responsibility
      in designing an environment that supports health and healing among its own
      employees. A program called WorkHealth, a comprehensive delivery system
      encompassing four integrated continuums directed toward individual employees,
      work teams, the organization as a whole, and the organization's relationship with
      the community, is described. Particular attention is focused on the health,
      wellness, and productivity of individuals and teams with recommendations for
      leaders in creating the environment for this to occur.

PMID- 8550694
TI  - [Arteriovenous and arterial-digestive system fistulas complicating isolated iliac
      aneurysm].
AB  - Isolated iliac aneurysms are often discovered when they rupture, sometimes into a
      neighbouring organ. We report 2 cases of aneurysm of the common iliac artery, one
      which ruptured into the right common iliac vein and the other in to the sigmoid.
      Diagnosis was made at laparotomy in the first case and on the CT-scan of the
      pelvis in the second. The first case was treated with an exclusion graft using
      ilio-iliac bypass with suture of the venous breach via the aneurysm. In the
      second case, the aneurysm was excluded by ligature of the iliac arteries with
      extra-anatomic crossed femoro-femoral bypass, sigmoid colostomy and drainage of
      the pelvis. These two cases illustrate the importance of digital examination of
      the pelvis and CT-scan for the diagnosis of complicated aneurysms of the iliac
      vessels. Rapid surgery is a determining factor in prognosis.

PMID- 8550695
TI  - [Urogenital injuries caused by projectiles. Data on recent conflicts and the
      North-American civilian experience].
AB  - The study of medical series from Vietnam and Lebanon, the analysis of US Army
      medical organization during recent UNO-IRAK conflict, the major technical
      contribution of North-American civilian publications should lead to draw correct
      organizational and technical management principles concerning genito urinary
      wounds, a for a long time misunderstood or neglected chapter of abdominal wounds.

PMID- 8550696
TI  - [Celioscopic treatment of acute obstructions caused by adhesions of the small
      intestine. Experience of 35 cases].
AB  - Postoperative adhesions are the primary cause of occlusion of the small bowel. We
      evaluated the feasibility and the immediate postoperative results of laparoscopic
      procedures for acute adhesions on the small bowel. Between September 1992 and
      March 1995, we performed laparoscopic procedures in 35 patients with acute
      occlusion of the small bowel. The preoperative work-up highly suggestive of
      adhesion. There were 17 males and 18 females, mean age 48.2 years. In 30
      patients, the operation confirmed the preoperative diagnosis of occlusion by
      adhesions. Lysis was performed entirely via the laparoscopic route in 21 of the
      30 patients (70%). Immediate postoperative complications were 3 bowel lesions.
      Intestinal mobility was re-established in 1.8 days after operation and the mean
      duration of hospitalization was 5 days for patients with laparoscopic procedure
      alone compared with 3.4 days for intestinal mobility and 10.4 days
      hospitalization for the 9 patients who were converted to laparotomy. An
      eventration of the trocar orifice occurred late in one patient and ischaemic
      stenosis of the bowel required laparotomy in another. There were no deaths.
      Laparoscopic treatment of adhesion occlusions is a feasible operation. Morbidity
      is low in experienced hands. The immediate benefit is rapid intestinal mobility
      and shorter hospital stay. The effect on long-term risk to be evaluated.

PMID- 8550697
TI  - [Thoughts on the role of celiosurgery in patients with major obesity].
AB  - Is coelioscopic surgery an interesting way in massive obese patients? This is
      well established concerning the post-operative benefit, with a decreased risk of
      pulmonary and thrombo-embolic complications. But technical difficulties are not
      well described, whereas we encountered some: incomplete retraction of intra
      abdominal organs, weakness and hemorrhagic tendency of the tissues, and most of
      all an insufficient pneumoperitoneum in all patients preventing sometime the
      surgical procedure. We analyse those obstacles to propose solutions when the
      laparoscopic way seems better regarding to the post-operative risk. We study
      their predictive factors, the best one being the thickness of the abdominal
      anterior wall, whereas the body weigh is an inadequate factor.

PMID- 8550698
TI  - [Palliative celioscopic gastrojejunal anastomosis in the treatment of neoplastic
      duodenal stenoses].
AB  - Gastroenterostomy procedure is actually the best palliative treatment for
      malignant duodenal obstruction, unresectable or with hepatic metastases. The
      authors reported a technique by laparoscopic way. This technique has been
      performed in 30d patients with good results.

PMID- 8550699
TI  - [Post-appendectomy fistulas of the cecum. Apropos of 22 cases].
AB  - Appendicitis, usually a benign disease, can have its prognosis worsened in case
      of postoperative fistula. The latter occurs rarely after open appendectomy
      (0.133%), but accounts for 10% of the morbidity rate. The authors reviewed 22
      cases of these fistulas, treated during a 24-year period (January 1970 to
      December 1993). The aim of these retrospective study was to precise their
      clinical features, to evaluate paraclinical examinations in diagnosing these
      complications and to give guidelines for their treatment. Fistulas occurred at
      day 14 in the postoperative course. In 21 case, appendicitis was severe
      (suppurative, gangrenous or perforated) or appendectomy quoted as technically
      difficult. Location of the appendix was atypical in 7 cases. Drainage of the site
      was performed in 17 cases at the time of appendectomy. Diagnosis was made on the
      aspect of the drainage fluid in 14 cases. Diagnosis workup of the fistula
      associated plain abdominal radiograph and abdominal ultrasonography (n = 22).
      Fistulography (n = 6) confirmed the clinical diagnosis of fistula, showing the
      leaking in all cases. Medical treatment was attempted first in 14 cases and was
      successful in 11 cases with a healing time from 13 to 72 days. Surgical treatment
      (open drainage of the site) was attempted first in 11 cases, and was mandatory in
      3 other cases because of medical treatment failure: one patient died and 5
      patients underwent re-operation (right colectomy in 3 cases, bypass in 1 case and
      re-drainage in 1 case). Fistulography in our experience, is highly reliable and
      is considered to be a great assistance in management of these fistulas. Medical
      treatment remains the best initial treatment modality. Surgery must be
      contemplated in case of established external fistulas, and of purulent or faecal
      fistulas. Nevertheless, prognosis remains poor (50% re-operation rate).

PMID- 8550700
TI  - [Surgical complications of intestinal ascariasis].
AB  - Ascaridiosis is a usually benign disease caused by the parasite Ascaris
      lumbricoides. Medical treatment is usually sufficient. Prevalence in tropical
      zones is high, sometimes leading to severe surgical complications requiring
      treatment and having a high morbidity and mortality. Codified treatments are
      needed to reduce the incidence of ascaridiosis. Large scale prevention is needed,
      especially in endemic zones.

PMID- 8550701
TI  - [Mucocele of the appendix: value of excision by celioscopy].
AB  - A mucocele of the appendix was complicated by appendicular volvulus. The CT-scan
      findings suggested the diagnosis which was confirmed at laparoscopy. This case
      illustrates the contribution of laparoscopy in diagnosis and treatment of
      mucoceles of the appendix.

PMID- 8550702
TI  - [The chief clinician of universities--resident of hospitals: his pedagogic
      impact].
AB  - When a resident is named "Chef de Clinique des Universites-Assistant des
      Hopitaux" he has reached the top rung of specialist's training in France. In
      addition to his role within the hospital ("Assistant des Hopitaux"), a role
      learned during the residentship, the title of "Chef de Clinique des Universites"
      means that he has a teaching role which is acquired intuitively on the basis of
      experience rather than actually being taught. The resident is given no special
      training before, as a young "Chef", he is called upon to teach medical students,
      residents, nurses, physical therapists or even patients under the authority of a
      professor. Teaching is done in various distinct locations (University and
      hospital: bedside, operating theatre, emergency room, consultations) which
      further complicates the new situation. The aim of this work was to
      retrospectively examine the teaching role of the "Chef de Clinique" based on
      personal experience both as a resident and as "Chef". Personal experience is
      given as an introduction to each paragraph.

PMID- 8550703
TI  - [A rare etiology of an abscess of the psoas: brucellosis. Apropos of 2 cases].

PMID- 8550704
TI  - [Evolution of Hartmann's procedure. 249 interventions].
AB  - A retrospective study of 249 patients undergoing Hartmann's procedure over twenty
      five years was undertaken to analyse the evolution of indications and results.
      Patients were divided into three time period groups: from 1969 to 1978, 1979 to
      1990 and 1991 to 1994. Mean age was 68 years old. Major indications were
      complicated diverticular disease (42.9%), colo-rectal malignancies (35.7%) and
      ischemic colitis (14%). Operative mortality is 10.8%, higher in ischemic colitis
      (20%) than in complicated diverticulitis (6.5%) and cancer (13.4%). Overall
      morbidity has significantly reduced, from 65.51% to 17.24%. General complications
      have changed a little, while local and/or inherent operative complications have
      reduced from 22.4% to 1.72. Restoration of colorectal continuity was done in
      59.54% of patients, increasing from 36% to 71% during the three periods. This is
      variable depending on initial disease: 92% in diverticular disease, 69% in
      ischemic colitis but remains stable for carcinoma at 33%. Overall mortality since
      1981 is 2.5% and morbidity is 19.13%. Mean Hospital stay was 20 days for the
      initial operation and 15 days for secondary restoration of colorectal continuity.
      Hartmann's procedure is well indicated as emergency surgery in colonic
      perforations, abscessus and ischemia. Progressive improvement of its results is
      essentially due to persistent attention to indications and technical details.

PMID- 8550705
TI  - [Surgical treatment of adenocarcinoma of the stomach: 1969-1994. Apropos of 261
      cases].
AB  - The study concerned 261 cases of gastric adenocarcinoma operated on between 1969
      and 1994. Clinical, histological and therapeutic features were analyzed and
      compared during 3 periods (Group 1: 1969-78, Group 2: 1979-88, Group 3: 1989-94).
      The aim was to evaluate changes and results occurred in gastric carcinoma. The
      median age was 65 years (rage 25-90 years), the sex ratio, 1.9. The most common
      location was in the lower third of the stomach and the cancer was often far
      advanced (73 percent of stages III and IV). Subtotal gastrectomy was replaced by
      total gastrectomy; the number of distal gastrectomy was unchanged. Large lymph
      node dissection was systematically performed in group 3. Curative resection rate
      increased from 28 to 51 percent between group 1 and group 3. Despite the more
      radical surgery, morbidity and post operative mortality rates decreased
      (respectively: 44.5%, 33%, 25.4%, and 22%, 10%, 7.2% for the groups 1, 2, 3, p <
      0.01). 2-year survival rates were 20 percent for group 1, 25 percent for group 2
      and 32 percent for group 3 (p < 0.01). This rates can be considered as satisfying
      in view of the high rate of III and IV stages.

PMID- 8550706
TI  - [Treatment of esophageal fistulas after gastrectomy. Apropos of 4 cases].
AB  - The authors report 4 cases of esophageal fistula following a total gastrectomy.
      One patient died after a reoperation for a subphrenic abscess, another just
      before a coloplasty 3 months after an esophageal exclusion. Two patients have
      been successfully treated by an operation which comprised the removal of the
      fistula and an intra-thoracic esophago-jejunal anastomosis. This procedure,
      albeit risked, is probably a better option than the esophageal exclusion usually
      recommended, particularly in the patients with a malignant disease who have a
      short life expectancy.

PMID- 8550707
TI  - [Impact of celioscopic surgery in general and digestive system surgery].
AB  - A retrospective study was conducted to evaluate the impact of laparoscopic
      surgery on activity in general and digestive surgery. From May 1990 to December
      1994, 2256 laparoscopic procedures were performed for cholecystectomy (36%),
      appendicectomy (20.4%) or inguinal hernia (19.8%). 23.2% of all procedures
      performed in 1994 were done laparoscopically. The use of laparoscopy did not, in
      our experience, added any new indications from 1988 to 1994. The conversion rate
      was 8.15%. 24% of the conversion cases could not be predicted. Mortality was
      0.18% and 1.19% of the patients had to undergo a second operation due to
      complications of laparsocopic surgery. The impact of laparoscopic procedures, 7
      years after the first laparoscopic cholecystectomy has been great. The results of
      this surgical technique must be evaluated to determine its medical and economic
      impact.

PMID- 8550708
TI  - [Atrio-caval shunt in injury to the suprahepatic vena cava. Apropos of a case and
      review of the literature].
AB  - Mortality in cases of trauma-induced lesions of the suprahepatic vena cava is
      high because it is difficult to expose the lesions, and consequently to control
      blood loss. Several techniques have been reported for treating this type of
      lesion. We report a case in which both suprahepatic veins were sutured after
      installing an atrio-cava shunt via a sternotomy. The limitations of this
      technique and other surgical possibilities are also discussed.

PMID- 8550709
TI  - [Internal pancreatic fistula: surgical treatment].
AB  - The authors present 13 cases of internal pancreatic fistula, of which 11 were
      secondary to a chronic pancreatitis and two were caused by an abdominal trauma.
      Beside the clinical picture, the diagnosis was anticipated by the high amylase
      levels present in the fluid obtained by paracentesis or thoracocentesis. The
      diagnosis was confirmed by the radiological analysis of the pancreatic duct
      system, when an endoscopic retrograde pancreatography was performed in seven
      patients, one pancreatography was carried out during surgery in five cases, and
      one patient underwent an injection of hydrosoluble contrast in the pleural
      cavity. The treatment was a latero-lateral pancreaticojejunoanastomosis in five
      cases, associated with a corpora-caudal pancreatectomy in four patients; a
      cephalic duodenopancreatectomy was performed in one case. Two patients underwent
      a cystoenteroanastomosis, while the option chosen in the last four cases was an
      external drainage. One patient refused to undergo surgical treatment. Operation
      mortality was null. The conclusion was that an adequate surgical treatment
      results in the occlusion of the internal pancreatic fistula and, furthermore,
      allows for the definitive resolution of underlying pancreatic affection.

PMID- 8550711
TI  - [Splenic peliosis. Apropos of 2 cases].
AB  - Two cases of splenic peliosis are reported. Clinical and radiographic signs and
      laboratory results do not contribute greatly to diagnosis which is based on
      histology findings. Splenic rupture is the major complication and requires
      immediate splenectomy.

PMID- 8550710
TI  - [Treatment of caustic stenoses of the upper digestive tract].
AB  - Stenosis of the upper digestive tract developed in 22 patients with stage IIB or
      stage III caustic burns due to massive ingestion of an alkaline substance in 18
      cases and an acid substance in 4 cases is analysed. Emergency oesogastrectomy
      without thoracotomy was performed in emergency situations in 10 patients in whom
      mortality reached 30%. For the remaining 12 patients with minimal stage IIB
      lesions, a jejunostomy was opened for enteral nutrition. After three months,
      stenosis developed in 10 cases and required surgical treatment in 7 after failure
      of endoscopic dilatations. Surgery included retrosternal coloplasy with
      oesophagectomy for 3 patients. There were no deaths. Two patients with a stenosis
      of the cervical anastomosis were treated endoscopically. These results suggest
      that the use of the endoscope in the acute phase can help ascertain the best
      management technique and confirms that stage IIB stenosis can develop a tight
      stenosis in 50% of the cases. This situation requires surgical treatment in 70%
      of the cases.

PMID- 8550712
TI  - [Acute stomach volvulus complicating hiatal hernia revealed by common bile duct
      calculi].
AB  - The authors report about one observation of acute gastric volvulus on
      paraoesophageal hiatus hernia caused by a choledocholithiasis, requiring
      gastrectomy and choledochotomy in emergency. On the basis of this case they sum
      up the main characteristics of this complication of hiatus hernia and insist on a
      earlier diagnosis before stage of irreversible lesions.

PMID- 8550713
TI  - [Gastroesophageal reflux. Conventional surgery versus laparoscopic treatment.
      Prospective study (61 cases). Mano-Ph-metric evaluation at 4 months].
AB  - 61 patients with aggressive gastro-esophageal reflux have been prospectively
      treated, 29 by open surgery and 32 by laparoscopy. There is no mortality and the
      morbidity is not significantly different (3 per cent vs 5 per cent). Hospital
      stay is strongly reduced in the laparoscopic group (5.4 days vs 8.9 days p =
      0.02). Either the period of no professional activity (21.3 days vs 38.2 days p =
      0.02). In both group, dysphagia is noted in 30% of the patients at 1 month and 3%
      at 4 months. All patients have had pre-operatively a mano-Ph-metry evaluation. At
      4 months, the follow-up rate is 100% and all patient have been controlled with a
      24 hours mano-Ph-metry. There is no difference between open and laparoscopic
      surgery. The mean SIO pressure had increased in both group from 3.6 mmHg to 18.1
      mmHg (p = 0.001). There is only one failure in the beginning of the learning
      curve (4th patients in the "laparoscopy group" (3.1%). These study suggest that
      laparoscopic treatment could be proposed in the majority of failures of medical
      treatment in gastro-oesophageal reflux.

PMID- 8550714
TI  - [Laparoscopy for appendicular syndromes in young women. Results of a prospective
      study].
AB  - OBJECTIVES: Determine whether laparoscopic surgery for painful syndromes of the
      right iliac fossa in young women can reduce the number of unnecessary
      appendectomies and shorten hospital stay. METHODS: Thirty-two women (age range 15
      43 years) who were admitted consecutively for "acute appendicitis" were included
      in a prospective study based on laparoscopic surgery for diagnosis and treatment.
      RESULTS: There were 14 cases of acute appendicitis (all confirmed
      histologically), 16 cases involving extra-appendicular tissues (mainly
      salpingitis, n = 7) and 2 cases in which no cause was found. Two unnecessary
      appendectomies were performed and only one laparoscopy had to be converted to an
      open procedure. Mean post-operative hospitalization was 3.43 days. These findings
      demonstrate that laparoscopic surgery effectively reduces the rate of unnecessary
      appendectomies and probably the duration of hospitalization. Laparoscopic surgery
      should be more widely used for young women presenting with appendicular
      syndromes.

PMID- 8550715
TI  - [Total gastrectomy and viscerosynthesis].
AB  - A retrospective study of 134 total gastrectomies performed between 1982 and 1992
      was conducted with regular follow-up. There were 96 males and 38 women (mean age
      66.66 years, range 27-82). The indication for total gastrectomy was malignant
      tumour (n = 115), mostly adenocarcinoma (79.1%, 91/115) with 7 cases of stump
      degeneration after partial gastrectomy (5.2%) and benign lesions (n = 19), mostly
      gastric ulcers. Gastrectomy was associated with node dissection in 53 cancer
      cases (47.8% 53/115) and dissection of neighbouring organs in 16 patients. Y
      anastomosis with circular mechanical suture was performed in 78 cases (62.9%)
      with pre-stapling in 30 (38.5%). Operative mortality was 8.2% (11/134). The
      oesophagealjejunal disunion occurred in 7/133 patients (5.3%) including two fatal
      cases. Early reoperation was necessary in 10.5%. Long-term follow-up for 2 to 12
      years in 119 patients gave the following data. For malignant tumours: 5-year
      survival rate 10.1% (n = 8), recurrence an anastomosis 6.3% (n = 5), distant
      recurrence 28.2% (n = 21). For all patients sequellae were: reflux oesophagitis
      8.1% (n = 10), stenosis of the anastomosis 7.3% (n = 9) requiring late
      reoperation in 2. The quality of life was considered satisfactory by 28.57% (n =
      8) and good in 39.29% (n = 11). These results were compared with those reported
      in the literature and led to the conclusion that the general view as to the
      gravity of gastrectomy should be reconsidered in light of the progress in
      viscerostapling.